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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 1541. Отображено 100.
02-02-2012 дата публикации

Pharmaceutical compositions for terminating acute episodes of cardiac arrhythmia, restoring sinus rhythm, preventing recurrence of cardiac arrhythmia and/or maintaining normal sinus rhythm in mammals

Номер: US20120028992A1
Автор: Arthur M. Brown
Принадлежит: Individual

Disclosed are pharmaceutical compositions for and methods of preventing or treating acute and/or chronic cardiac arrhythmias in a mammal, including terminating acute episodes of cardiac arrhythmia, restoring normal sinus rhythm, preventing recurrence of cardiac arrhythmia and/or maintaining normal sinus rhythm, which contain a combination of 1-[2-[(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine.

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Номер записи: 1
21-03-2013 дата публикации

TREATMENT OF T-CELL MEDIATED DISEASES

Номер: US20130071436A1
Автор: Bar-Or David, Bar-Or Raphael, Shimonkevitz Richard
Принадлежит: DMI BIOSCIENCES, INC.

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A method of treating inflammation or an inflammatory disease involving , caused by or exacerbated by T-cells , comprising administering to an animal in need thereof an effective amount of a pharmaceutical composition comprising a filtrate of a solution of a protein or peptide , wherein the filtrate is produced by passing the solution of a protein or peptide over an ultrafiltration membrane with a molecular weight cutoff that retains a protein selected from the group consisting of albumin , immunoglobulin and erythropoietin , and wherein the filtrate comprises: a diketopiperazine selected from the group consisting of YE-DKP , MR-DKP and DA-DKP.93. The method of wherein the filtrate contains components having molecular weights less than 3000.94. The method of wherein the protein or peptide is a human protein or peptide.95. The method of wherein the protein or peptide is a human albumin.96. The method of wherein the protein or peptide is a human protein or peptide.97. The method of wherein the protein or peptide is a human albumin.98. The method of wherein the animal is a human.99. A method of reducing the symptoms claim 92 , severity or both of a T-cell mediated disease claim 92 , comprising administering to an animal in need thereof an effective amount of a pharmaceutical composition comprising a filtrate of a solution of a protein or peptide claim 92 , wherein the filtrate is produced by passing the ...

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Номер записи: 2
21-03-2013 дата публикации

TREATMENT OF T-CELL MEDIATED DISEASES

Номер: US20130071448A1
Автор: Bar-Or David, Bar-Or Raphael, Shimonkevitz Richard
Принадлежит: DMI BIOSCIENCES, INC.

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A container comprising a pharmaceutical formulation , wherein the formulation comprises a filtrate of a solution of a protein or peptide produced by passing the solution of a protein or peptide over an ultrafiltration membrane with a molecular weight cutoff that retains a protein selected from the group consisting of albumin , immunoglobulin and erythropoietin , and wherein the filtrate comprises a diketopiperazine selected from the group consisting of YE-DKP , MR-DKP and DA-DKP.93. The container of claim 92 , wherein the container comprises a unit dose of the pharmaceutical formulation.94. The container of claim 92 , wherein the container comprises multiple doses of the pharmaceutical formulation.95. The container of claim 92 , wherein the filtrate contains components having molecular weights less than 3000.96. The container of wherein the protein or peptide is a human protein or peptide.97. The container of wherein the protein or peptide is a human albumin.98. The container of wherein the protein or peptide is a human protein or peptide.99. The container of wherein the protein or peptide is a human albumin.100. The container of claim 92 , wherein the filtrate is lyophilized.101. The container of claim 100 , wherein in the filtrate is in a form selected from the group consisting of powders claim 100 , granules and tablets.102. The container of claim 100 , wherein a sterile liquid carrier is added to the ...

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Номер записи: 3
21-03-2013 дата публикации

TREATMENT OF T-CELL MEDIATED DISEASES

Номер: US20130072684A1
Автор: Bar-Or David, Bar-Or Raphael, Shimonkevitz Richard
Принадлежит: DMI BIOSCIENCES, INC.

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions. 191-. (canceled)92. A pharmaceutical composition comprising a diketopiperazine (DKP)-containing fraction of a solution of a protein or peptide , wherein the DKP-containing fraction is produced by separating a protein or peptide selected from the group consisting of albumin , immunoglobulin and erythropoietin from the solution of a protein or peptide , wherein the DKP is selected from the group consisting of YE-DKP , MR-DKP and DA-DKP.93. The composition of wherein the DKP-containing fraction contains components having molecular weights less than 3000.94. The composition of wherein the protein or peptide is a human protein or peptide.95. The composition of wherein the protein or peptide is a human albumin.96. The composition of wherein the protein or peptide is a human protein or peptide.97. The composition of wherein the protein or peptide is a human albumin.98. The composition of claim 92 , wherein the DKP-containing fraction is separated from the solution of the protein or peptide by a separation method selected from the group consisting of size exclusion chromatography claim 92 , affinity chromatography claim 92 , anion exchange chromatography claim 92 , cation exchange chromatography and filtration.99. A DKP-containing fraction produced by separating a protein or peptide from a solution of a protein or peptide selected from the group consisting of albumin claim 92 , immunoglobulin and erythropoietin claim 92 , wherein the ...

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Номер записи: 4
04-04-2013 дата публикации

USE OF LEVOCETIRIZINE AND MONTELUKAST IN THE TREATMENT OF INFLUENZA, COMMON COLD AND INFLAMMATION

Номер: US20130085124A1
Автор: May Bruce Chandler
Принадлежит:

The embodiments described herein include methods and formulations for treating influenza, common cold and associated acute inflammation. The methods and formulations include, but are not limited to, methods and formulations for delivering effective concentrations of levocetirizine and montelukast to a patient in need. The methods and formulations can comprise conventional and/or modified-release elements, providing for drug delivery to the patient. 1. A method of treating chronic inflammation in a patient in need thereof comprising administering to the patient an effective amount of a combination of levocetirizine and montelukast.2. The method of claim 1 , wherein the chronic inflammation is non-IgE-mediated inflammation.3. The method of claim 1 , wherein the chronic inflammation is chronic rhinosinusitis.4. The method of claim 1 , wherein the chronic inflammation IS a combination of non-IgE-mediated and IgE-mediated inflammation.5. The method of claim 1 , wherein the patient has nasal polyps.6. The method of claim 1 , wherein the combination is administered in a sequential manner.7. The method of claim 1 , wherein the combination is administered in a substantially simultaneous manner.8. The method of claim 1 , further comprising the administration of a steroid.9. The method of claim 1 , wherein the combination is administered to the patient by one or more of the routes consisting of enteral claim 1 , intravenous claim 1 , intraperitoneal claim 1 , inhalation claim 1 , intramuscular claim 1 , subcutaneous and oral.10. The method of claim 9 , wherein the levocetirizine and montelukast are administered by the same route.11. A method of treating acute nasal and sinus inflammation in a patient in need thereof comprising administering to the patient an effective amount of a combination of levocetirizine and montelukast.12. The method of claim 11 , wherein the acute inflammation is caused by a viral infection.13. The method of claim 12 , wherein the viral infection is ...

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Номер записи: 5
25-04-2013 дата публикации

METHOD OF TREATING DIABETES

Номер: US20130102555A1
Автор: Jerling Markus, Wolff Andrew
Принадлежит: Gilead Sciences, Inc.

Methods are provided for treating diabetes, lowering plasma level of HbA1c, glucose plasma levels, total cholesterol plasma level, and/or triglyceride plasma level while increasing HDL cholesterol levels and delaying onset of diabetic retinopathy in a diabetic, pre-diabetic, or non-diabetic mammal while minimizing undesirable side effects. 142-. (canceled)43. A method of treating diabetes in a human patient in need thereof , comprising administering to the patient a therapeutically effective amount of ranolazine , which is named N-(2 ,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-1-piperazineacetamide , as a racemic mixture or a pharmaceutically acceptable salt thereof , and a therapeutically effective amount of an agent selected from the group consisting of sulfonylurea , meglitinide , biguanide , thazolidinedione , alpha glucosidase inhibitor and ACE inhibitor.44. The method of claim 43 , wherein the sulfonylurea is selected from chlorpropamide claim 43 , tolbutamide claim 43 , glyburide claim 43 , glipizide claim 43 , and glimepiride.44. The method of claim 43 , wherein the meglitinide is reparglinide or nateglinide.45. The method of claim 43 , wherein the biguanide is metformin.46. The method of claim 43 , wherein the thazolidinedione is selected from the group consisting of troglitazone claim 43 , pioglitazone and rosiglitazone.47. The method of claim 43 , wherein the alpha glucosidase inhibitor is acarbose or miglitol.48. The method of claim 43 , wherein the ACE inhibitor is hydrochlorothazide.49. The method of claim 43 , wherein the patient is not on insulin.50. The method of claim 43 , wherein the patient is non-insulin dependent. This is a Continuation of U.S. patent application Ser. No. 10/443,314, filed May 21, 2003, which claims priority to U.S. Provisional Application Ser. No. 60/382,781, filed May 21, 2002, and to U.S. Provisional Application Ser. No. 60/459,332, filed Mar. 31, 2003, the complete disclosures of which are hereby ...

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Номер записи: 6
16-05-2013 дата публикации

METHODS OF TARGETING PTEN MUTANT DISEASES AND COMPOSITIONS THEREFOR

Номер: US20130123273A1
Автор: Feher Miklos, Mason Jacqueline M., Pan Guohua, Wei Xin
Принадлежит: UNIVERSITY HEALTH NETWORK

Provided herein are methods, uses and compositions for treating a patient with cancer wherein the cancer is characterized by a PTEN gene mutation. In particular embodiments, the methods comprise administering to the patient a composition comprising a therapeutically effective amount of a PLK4 antagonist, and identifying a patient that is likely to be responsive to PLK4 antagonist therapy, if PTEN gene mutation is present. 1. A method of treating a patient with cancer , wherein said cancer is characterized by a PTEN gene mutation , the method comprising administering to the patient a composition comprising a therapeutically effective amount of a PLK4 antagonist.2. The method of claim 1 , wherein the PTEN gene mutation results in reduced expression of PTEN as compared to a normal control claim 1 , expression of a non-functional or limited functioning PTEN protein claim 1 , or a loss of PTEN expression.3. The method of claim 1 , wherein the cancer is breast cancer claim 1 , prostate cancer claim 1 , endometrial cancer claim 1 , ovarian cancer claim 1 , brain cancer claim 1 , skin cancer claim 1 , thyroid cancer claim 1 , lung cancer claim 1 , bladder cancer claim 1 , colon cancer claim 1 , melanoma claim 1 , glioblastoma or lymphoma.4. The method of claim 3 , wherein the cancer is a breast cancer selected from the subtypes: HER2-overexpressing claim 3 , luminal A claim 3 , luminal B claim 3 , and normal breast-like.5. The method of claim 3 , wherein the cancer is a basal subtype breast cancer.6. The method of claim 1 , wherein the PLK4 antagonist is a small molecule inhibitor.7. (canceled)8. A method of identifying a cancer patient that is likely to be responsive to PLK4 antagonist therapy claim 1 , comprising:(a) providing a suitable sample from a cancer patient; and(b) determining PTEN expression in said sample;wherein if said sample is characterized by a PTEN mutation as compared with a suitable control then the patient is likely to be responsive to PLK4 antagonist ...

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Номер записи: 7
16-05-2013 дата публикации

PRODUCTION OF ALDEHYDES BY OXIDATION IN AQUEOUS MEDIUM WITH SELECTIVE RECOVERY OF THE PRODUCT BY MEANS OF PERVAPORATION

Номер: US20130123546A1
Автор: Augugliaro Vincenzo, Camer Roda Giovanni, Loddo Vittorio, Palmisano Giovanni, Palmisano Leonardo
Принадлежит: ALMA MATER STUDIORUM UNIVERSITA DI BOLOGNA

A process for the preparation of an aromatic aldehyde by means of the oxidation of the corresponding starting compound in aqueous medium, and separation of said aldehyde from said medium by pervaporation is disclosed together a plant for its carrying out. Advantageously, the process of the present invention allows control of oxidation reaction and recovery of the product with high selectivity and purity. Among others, benzaldehyde, anisaldehyde and vanillin can advantageously be prepared by this process. 1. A process for the preparation of an aromatic aldehyde comprising oxidizing corresponding starting compound in aqueous medium , and separating aldehyde from said medium by pervaporation through an organophilic membrane.2. The process according to claim 1 , wherein said process is carried out in semi-continuous or continuous mode.3. The process according to claim 2 , wherein unreacted claim 2 , corresponding starting compound is recycled.4. The process according to claim 1 , wherein the corresponding starting compound is a primary aryl aliphatic alcohol.5. The process according to claim 4 , wherein said primary alcohol claim 4 , is selected from the group consisting of benzyl alcohol claim 4 , 4-methoxybenzyl alcohol claim 4 , 4-hydroxy-3-methoxybenzyl alcohol claim 4 , 4-nitrobenzyl alcohol claim 4 , 4-methylbenzyl alcohol claim 4 , 4-(trifluoro)methylbenzyl alcohol claim 4 , 4-tertiarybutylbenzyl alcohol claim 4 , 4-hydroxylbenzyl alcohol and 2-phenylethanol.6. The process according to claim 1 , wherein the corresponding starting compound is an alkenyl benzene.7. The process according to claim 6 , wherein said alkenyl benzene is selected from the group consisting of 4-allyl-2-methoxy phenol claim 6 , 2-methoxy-4-(1-propenyl)phenol claim 6 , hydroxylated alkenyl aromatics claim 6 , and (E)-3-(4-hydroxy-3-methoxy-phenyl)prop-2-enoic acid.8. The process according to claim 1 , wherein said oxidizing comprises catalytic photo-oxidation.9. The process according to ...

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Номер записи: 8
23-05-2013 дата публикации

PHARMACEUTICAL COMPOSITIONS INCLUDING CARBAMOYLOXY ARYLALKANOYL ARYLPIPERAZINE COMPOUND

Номер: US20130131081A1
Автор: Chae Eun Hee, Chae Sang Mi, Moon Hong Sik, Shin Hye Won, Yi Han Ju
Принадлежит: SK BIOPHARMACEUTICALS CO., LTD.

A pharmaceutical composition that includes a carbamoyloxy arylalkanoyl arylpiperazine compound SERUM CHOLESTEROL and effectively prevents or treats diabetic nephropathy, diabetic neuropathy, diabetic vascular complications, hyperlipidemia, coronary artery disease, or inflammation. 14.-. (canceled)6. The method of claim 5 , wherein the compound has an inhibitory activity of 15-lipoxygenase.7. The method of claim 5 , wherein the disease associated with 15-lipoxygenase is selected from the group consisting of diabetic complications claim 5 , hyperlipidemia claim 5 , coronary artery disease claim 5 , and inflammation.8. The method of claim 7 , wherein the diabetic complications includes diabetic nephropathy claim 7 , diabetic neuropathy claim 7 , diabetic vascular complications claim 7 , diabetic hyperlipidemia and diabetic inflammation.9. The method of claim 5 , wherein the compound is selected from the group consisting of:carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazine-1-yl]-3-oxo-1-phenyl-propyl ester;carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazine-1-yl]-1-(4-fluoro-phenyl)-3-oxo-propyl ester;carbamic acid 3-(4-benzo[1,3]dioxol-5-yl-piperazine-1-yl)-3-oxo-1-phenyl-propyl ester;carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazine-1-yl]-1-(4-trifluoromethyl-phenyl)-3-oxo-propyl ester, hydrochloride;carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazine-1-yl]-1-(4-nitro-phenyl)-3-oxo-propyl ester;(R)-carbamic acid 3-[4-(4-chloro-phenyl)-piperazine-1-yl]-3-oxo-1-phenyl-propyl ester;(S)-carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazine-1-yl]-3-oxo-1-phenyl-propyl ester;(R)-carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazine-1-yl]-3-oxo-1-phenyl-propyl ester;carbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazine-1-yl]-1-phenyl-butyl ester; andcarbamic acid 3-[4-(3,4-dimethoxy-phenyl)-piperazine-1-yl]-1-(4-chloro-phenyl)-3-oxo-propyl ester.10. The method of claim 7 , wherein the compound is selected from the group consisting of:carbamic acid 3-[4-(3,4-dimethoxy- ...

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Номер записи: 9
04-07-2013 дата публикации

PROCESS FOR PRODUCING A RINGLIKE OXIDIC SHAPED BODY

Номер: US20130172577A1
Автор: Borchert Holger, EGER Knut, Faust Jens Uwe, Mueller-Engel Klaus Joachim, Raichle Andreas, Streibert Ralf
Принадлежит: BASF SE

A process for producing a ringlike oxidic shaped body by mechanically compacting a pulverulent aggregate introduced into the fill chamber of a die, wherein the outer face of the resulting compact corresponds to that of a frustocone. 1. A ringlike oxidic shaped body obtained by a process comprising the mechanical compaction of a pulverulent aggregate which has been introduced into the fill chamber of a die and is composed of constituents which comprise at least one metal compound which can be converted to a metal oxide by thermal treatment at a temperature of ≧100° C. , or at least one metal oxide , or at least one metal oxide and at least one such metal compound , to give a ringlike shaped precursor body , in which the fill chamber is disposed in a die bore conducted through the die material from the top downward with a vertical bore axis B and is delimited bythe inner wall of the die bore,the upper end face of a lower punch introduced from below along the bore axis B into the die bore so as to be liftable and lowerable, on which the pulverulent aggregate introduced into the fill chamber rests,the lower end face, disposed along the bore axis B at an axial starting distance A above the upper end face of the lower punch, of an upper punch mounted so as to be liftable and lowerable along the bore axis B, whose lower end face is in contact with the pulverulent aggregate introduced into the fill chamber from above, andthe outer face of a center pin MF conducted from the bottom upward in the die bore along the bore axis B from the geometric center of the upper end face of the lower punch, said center pin MF extending at least up to the geometric center of the lower end face of the upper punch,the process comprising reducing the axial starting distance A of the two end faces along the bore axis B to an axial end distance E predefined for the compaction by lowering the upper punch while maintaining the position of the lower punch or additionally lifting the lower punch, ...

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Номер записи: 10
18-07-2013 дата публикации

2-(R2-THIO)-10-[3-(4-R1-PIPERAZIN-1-YL) PROPYL]-10H-PHENOTHIAZINE FOR TREATING A BETA-AMYLOIDOPATHY OR AN ALPHA-SYNUCLEOPATHY, AND METHOD FOR THE DIAGNOSIS OR PREDIAGNOSIS THEREOF

Номер: US20130184268A1
Автор: Pahnke Jens
Принадлежит: Immungenetics AG

The invention relates to 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to general formula I, for treating a β-amyloidopathy or an α-synucleinopathy accompanied by a cerebral protein deposit and a reduced activity of the cerebral ABCC1-transporter. The invention also relates to a method for the diagnosis or prediagnosis of a β-amyloidopathy or an α-synucleopathy accompanied by a cerebral protein deposit and a reduced activity of the cerebral ABCC1-transporter, or for determining the risk of a proband suffering from such an illness, the proband already having accumulated substances transported by the cerebral ABCC1 transporter. 2. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to claim 1 , characterized in that wherein the halogen atom/the halogen atoms are selected from the group consisting of fluorine and chlorine.3. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to claim 1 , wherein Rand Rare the same or different and each independently of one another is a C-Calkyl group.4. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to claim 1 , wherein the residues Rand Rare hydrogen.5. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to claim 1 , wherein the residue Ris a methyl group claim 1 , the residue Ris an ethyl group claim 1 , and the residues Rand Rare hydrogen.6. A composition comprising a 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazine according to claim 1 , further comprising a further active substance.7. A composition according to claim 6 , wherein a 1-benzohydrylpiperazine is a further active substance.8. A composition according to claim 7 , wherein 1-benzohydryl-4-cinnamyl piperazine is the 1-benzohydrylpiperazine.9. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H-phenothiazines according to claim 1 , wherein the β-amyloidopathy is Alzheimer's dementia.10. A 2-(R-thio)-10-[3-(4-R-piperazin-1-yl)propyl]-10H- ...

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Номер записи: 11
18-07-2013 дата публикации

SELF-EMULSIFYING FORMULATIONS AND METHODS OF USE THEREOF

Номер: US20130184290A1
Автор: GRIECO Elizabeth, Harianawala Abizer, Padval Mahesh V., SAXENA Vishal
Принадлежит:

The present invention relates to formulations and methods for increasing the bioavailability of 1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one, diphenylpropanoyl)piperazine, or a salt thereof. In particular, the formulation can include one or more self-emulsifying carriers. 1. A pharmaceutical composition in unit dosage form for oral administration , said composition comprising from about 20 mg to about 250 mg of compound 1 and a pharmaceutically acceptable carrier ,wherein, following administration of said pharmaceutical composition to subjects, the ratio of the mean bioavailability for fed subjects to the mean bioavailability for fasted subjects is from about 1.0 to about 2.0, andwherein said composition is self-emulsifying.2. A pharmaceutical composition in unit dosage form for oral administration , said composition comprising from about 20 mg to about 250 mg of compound 1 and a pharmaceutically acceptable carrier , wherein said composition is self-emulsifying.3. The pharmaceutical composition of claim 2 , wherein said composition comprises of from about 2% to about 10% (w/w) of said compound 1.4. The pharmaceutical composition of claim 1 , wherein the percentage loading of said compound 1 is of from about 0.1% to about 60% (w/w).5. The pharmaceutical composition of claim 2 , wherein said carrier comprises a lipophilic carrier and optionally a surfactant carrier.6. The pharmaceutical composition of claim 1 , wherein said unit dosage form comprises from about 20 mg to about 100 mg of compound 1.7. The pharmaceutical composition of claim 2 , wherein claim 2 , following administration of said pharmaceutical composition to fasted subjects claim 2 , the mean bioavailability is greater than about 20%.8. The pharmaceutical composition of claim 2 , wherein administration of said pharmaceutical composition to fed and fasted subjects produces a coefficient of variation in Cof less than about 60%.9. The pharmaceutical composition of claim 2 , wherein administration ...

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Номер записи: 12
18-07-2013 дата публикации

THERAPEUTIC USES OF 1-[2-(2,4-DIMETHYL-PHENYLSUFLANYL)PHENYL]PIPERAZINE

Номер: US20130184291A1
Автор: DRAGHEIM Marianne, FLOREA Ioana
Принадлежит: H. Lundbeck A/S

The invention provides new therapeutic uses of 1-[2-(2,4-dimethyl-phenylsulfanyl)phenyl]-piperazine and pharmaceutically acceptable salts thereof. 18-. (canceled)9. A method for the long-term treatment of a CNS disease comprising the long term administration of a therapeutically effective amount of 1-[2-(2 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof to a patient in need thereof wherein said administration is not associated with weight gain.10. A method for the treatment of a CNS disease in a patient in need thereof who has previously received medication (or is still receiving it) for the treatment of said disease which medication was ceased (or has to be ceased) due to weight related adverse events , the method comprising the administration of a therapeutically effective amount of 1-[2-(2 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof to said patient.11. A method for the treatment of a CNS disease in a patient in need thereof who is overweight , the method comprising the administration of a therapeutically effective amount of 1-[2-(2 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof to said patient.12. The method according to wherein said patient is characterised by a BMI above 25.13. A method for treatment of a CNS disease in a patient in a need thereof claim 11 , the method comprising the steps of a) determining the BMI of said patient; and b) administering a therapeutically effective amount of 1-[2-(2 claim 11 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof to said patient if the BMI is determined to be above 25.14. A method of treating a CNS disease in a patient in need thereof claim 11 , wherein said patient is suffering from a further disease wherein weight increase should be avoided claim 11 , the method comprising the administration of a therapeutically effective amount of 1-[2-(2 claim ...

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Номер записи: 13
01-08-2013 дата публикации

PROCESS FOR PREPARING ACROLEIN FROM GLYCEROL OR GLYCERIN

Номер: US20130197258A1
Автор: Belliere-Baca Virginie, Lauriol-Garbey Pascaline, Loridant Stéphane, Millet Jean-Marc
Принадлежит:

The invention concerns a method for preparing acrolein from glycerol or glycerine, wherein dehydration of the glycerol or glycerine is achieved in the presence of a catalyst based on zirconium oxide and which active phase consists in at least 1. A method for preparing acrolein from glycerol or glycerine , wherein dehydration of the glycerol or glycerine is achieved in the presence of a catalyst based on zirconium oxide and which active phase comprises at leasta) a silicon oxide, a zirconium oxide and at least one metal M oxide, said metal being selected from tungsten, cerium, manganese, niobium, tantalum, vanadium and titanium,b) a titanium oxide, a zirconium oxide and at least one metal M oxide, said metal being selected from tungsten, cerium, manganese, niobium, tantalum, vanadium and silicon.2. The method according to claim 1 , wherein the active phase comprises at least a silicon oxide claim 1 , a zirconium oxide claim 1 , a tungsten oxide and at least one metal M oxide claim 1 , said metal being selected from cerium claim 1 , manganese claim 1 , niobium claim 1 , tantalum claim 1 , vanadium and titanium claim 1 ,3. The method according to claim 2 , wherein the metal is titanium claim 2 ,4. The method according to claim 1 , wherein at least one of the oxides of said catalyst a) and b) is supported.5. The method according to claim 1 , wherein the (Zr/sum of the elements Si claim 1 , Ti claim 1 , W and M claim 1 , different from Zr) molar ratio varies from 0.5 to 200.6. The method according to claim 5 , wherein said molar ratio varies from 1 to 100.7. The method according to claim 1 , wherein the glycerol is in aqueous solution at a concentration of at least 1% by weight.8. The method according to claim 7 , wherein the glycerol concentration of the aqueous solution varies from 10 to 50% by weight.9. The method according to claim 1 , wherein the catalyst is regenerated.10. A method for making 3-(methylthio)propionic aldehyde MMP claim 1 , 2-hydroxy-4- claim 1 , ...

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Номер записи: 14
15-08-2013 дата публикации

PREPARATION OF BICYCLO[2.2.2]OCTAN-2-ONE COMPOUNDS

Номер: US20130211104A1
Автор: Abele Stefan, Funel Jacques-Alexis
Принадлежит: ACTELION PHARMACEUTICALS lTD,

The present invention relates to a new process for the preparation of 6-hydroxy-5-arylbicyclo[2.2.2]octan-2-one compounds of the formula (II); which may subsequently be further transformed to compounds of the formula (I): 6. The process according to claim 5 , wherein the compound of formula 1 is used in enantiomerically enriched form.10. The compound according to selected from the group consisting of:2-Phenyl-2-((R)-1,4-dioxaspiro[4.5]decan-7-yl)-acetaldehyde; and2-Phenyl-2-(1,4-dioxaspiro[4.5]decan-7-yl)-acetaldehyde.12. The compound according to selected from the group consisting of:2-Phenyl-2-((R)-1,4-dioxaspiro[4.5]decan-7-yl)-ethanol;2-Phenyl-2-(1,4-dioxaspiro[4.5]decan-7-yl)-ethanol;rac-(R*)-2-Phenyl-2-((R*)-1,4-dioxaspiro[4.5]decan-7-yl)-ethanol; andrac-(R*)-2-Phenyl-2-((S*)-1,4-dioxaspiro[4.5]decan-7-yl)-ethanol.14. The compound according to selected from the group consisting of:Methyl 2-phenyl-2-((R)-1,4-dioxaspiro[4.5]decan-7-yl)-acetate;Methyl 2-phenyl-2-(1,4-dioxaspiro[4.5]decan-7-yl)-acetate;rac-(R*)-Methyl 2-phenyl-2-((R*)-1,4-dioxaspiro[4.5]decan-7-yl)-acetate; andrac-(R*)-Methyl 2-phenyl-2-((S*)-1,4-dioxaspiro[4.5]decan-7-yl)-acetate.16. The compound according to selected from the group consisting of:2S,3S,4R)-6-oxo-3-phenylbicyclo[2.2.2]octan-2-ylmethanesulfonate; andrac-(1S*,2R*,3R*,4S*)-6-oxo-3-phenylbicyclo [2.2.2]octan-2-yl methanesulfonate. The present invention relates to a new process for the preparation of 6-hydroxy-5-arylbicyclo[2.2.2]octan-2-one compounds of the formula (II); which may subsequently be further transformed to compounds of the formula (I):The present invention further relates to novel compounds of formula 2, formula 3 and formula 4 as such. The present compounds of formula 2, formula 3 and formula 4 can be used as intermediates in the preparation of compounds of the formula (II). The present invention further relates to novel compounds of formula 6 as such. The present compounds of formula 6 can be used as intermediates in ...

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Номер записи: 15
29-08-2013 дата публикации

COMBINATION THERAPY WITH W T 1 PEPTIDE VACCINE AND TEMOZOLOMIDE

Номер: US20130225502A1
Автор: Hashimoto Naoya, SUGIYAMA Haruo, Tsuboi Akihiro, Yoshimine Toshiki
Принадлежит: INTERNATIONAL INSTITUTE OF CANCER IMMUNOLOGY, INC.

The present invention relates to combination therapy for cancer with a WT1 peptide vaccine and temozolomide. 1. A method for treating cancer , comprising administering therapeutically effective doses of a WT1 peptide and temozolomide to a patient in need thereof.3. The method according to claim 1 , wherein the cancer is glioma.4. The method according to claim 1 , wherein the WT1 peptide and temozolomide are administered to a patient having received extirpative surgery for tumor.5. The method according to claim 1 , wherein the WT1 peptide and temozolomide are administered to a patient having received radiation therapy.6. The method according to claim 1 , wherein the WT1 peptide and temozolomide are administered to a patient having received a combination therapy of radiation therapy and temozolomide. This application claims priority based on U.S. Provisional Application No. 61/552,209, filed Oct. 27, 2011 (incorporated herein by reference in its entirety).The present invention relates to combination therapy for cancer with a WT1 peptide vaccine and temozolomide. The present invention also relates to a pharmaceutical composition comprising a WT1 peptide, characterized by being used in combination with temozolomide.WT1 gene (Wilms' tumor 1 gene) is a gene identified as a causative gene for Wilms' tumor that is a childhood renal cancer, and encodes a transcription factor having a zinc finger structure. WT1 gene was initially considered to be a tumor suppressor gene. However, subsequent studies revealed that it rather functioned as an oncogene in a hematopoietic organ tumor and a solid cancer.It has been shown that the in vitro stimulation of peripheral blood mononuclear cells with a WT1 peptide induces cytotoxic T-lymphocytes (CTLs) specific for the peptide, which kill hematopoietic organ tumor or solid cancer cells endogenously expressing WT1. Various WT 1 peptides capable of inducing WT1-specific CTLs, which are expected to be used for cancer immunotherapy, have ...

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Номер записи: 16
26-09-2013 дата публикации

SULFONYL-SUBSTITUTED BICYCLIC COMPOUNDS AS PPAR MODULATORS FOR THE TREATMENT OF NON-ALCOHOLIC STEATOHEPATITIS

Номер: US20130252970A1
Автор: Grint Paul, Guha Mausumee
Принадлежит: KALYPSYS, INC.

Disclosed herein are new methods of treatment of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and other fibrotic diseases of the liver in a subject by modulating PPARδ with sulfonyl-substituted bicyclic compounds and compositions as pharmaceuticals. 2. The method as recited in claim 1 , wherein T is —C(O)OH.3. The method as recited in claim 2 , wherein A comprises a chain having three atoms and forming a five-membered ring.6. The method as recited in claim 5 , wherein A comprises a chain having three atoms and forms a five-membered ring.7. The method as recited in claim 5 , wherein Gis selected from the group consisting of a bond and methylene.8. The method as recited in claim 5 , wherein:p is 2;{'sub': 4', '5, 'W is CXX; and'}{'sub': '1', 'Yis N.'}9. The method as recited in claim 9 , wherein Gis optionally substituted aryl or optionally substituted heteroaryl.10. The method as recited in claim 9 , wherein Gis singly or doubly substituted with halogen claim 9 , lower alkyl claim 9 , lower perhaloalkyl claim 9 , lower perhaloalkoxy or mono- or di-haloalkoxy.11. The method as recited in claim 8 , wherein Yis N.12. The method as recited in claim 11 , wherein Gis selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl.13. The method as recited in claim 12 , wherein Gis optionally substituted phenyl or optionally substituted pyridinyl.14. The method as recited in claim 13 , wherein Gis singly or doubly substituted with halogen claim 13 , lower alkyl claim 13 , lower perhaloalkyl claim 13 , or lower perhaloalkoxy or mono- or di-haloalkoxy.15. The method as recited in claim 12 , wherein X claim 12 , X claim 12 , and Xare each independently selected from the group consisting of hydrogen claim 12 , lower alkyl claim 12 , perhaloalkyl claim 12 , and halogen.16. The method as recited in claim 15 , wherein X claim 15 , X claim 15 , and Xare independently selected from the group consisting of ...

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Номер записи: 17
26-09-2013 дата публикации

Ophthalmic Formulations of Cetirizine and Methods of Use

Номер: US20130252971A1
Автор: Abelson Mark Barry, Chapin Matthew J., Gomes Paul, Minno George, Nice Jackie
Принадлежит: ACIEX THERAPEUTICS, INC.

The present invention provides stable topical formulations of cetirizine that provide a comfortable formulation when instilled in the eye and is effective in the treatment of allergic conjunctivitis and/or allergic conjunctivitis. The invention further provides methods of treating allergic conjunctivitis and/or allergic rhinoconjunctivitis in a subject in need of such treatment by topical application of the cetirizine formulations of the invention directly to the eye. 1. A method for alleviating a sign or symptom of allergic conjunctivitis by topically administering to an eye of a subject in need thereof an ophthalmic formulation comprising a single active ingredient consisting of 0.24% (w/v) cetirizine.2. The method of wherein the formulation does not contain a cyclodextrin or other solubilizing compound.3. The method of claim 1 , wherein the ophthalmic formulation is administered twice daily.4. The method of claim 1 , wherein ophthalmic formulation is an aqueous formulation claim 1 , an ointment claim 1 , an oil claim 1 , a suspension claim 1 , an emulsion claim 1 , or incorporated in a drug delivery device.5. The method of claim 1 , wherein the ophthalmic formulation further comprises 1% Polyethylene Glycol 400 claim 1 , NF claim 1 , 0.2% Dibasic Sodium Phosphate claim 1 , Anhydrous claim 1 , USP claim 1 , 0.25% Hypromellose claim 1 , USP claim 1 , 0.1% Polysorbate 80 claim 1 , NF claim 1 , 1.8% Glycerin claim 1 , USP claim 1 , 0.01% Benzalkonium Chloride claim 1 , NF claim 1 , and Purified Water claim 1 , USP claim 1 , and wherein the formulation has a pH 6.8-7.2.6. The method of claim 1 , wherein the sign or symptom is itching.7. The method of claim 1 , wherein said subject has ocular itching claim 1 , ocular redness and lid swelling. This application is a divisional of U.S. application Ser. No. 12/724,128, filed Mar. 15, 2010, and claims priority to U.S. Provisional Application No. 61/161,006, filed Mar. 17, 2009 and U.S. Provisional Application No. 61/174,850 ...

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Номер записи: 18
03-10-2013 дата публикации

COMPOSITIONS AND METHODS FOR CANCER TREATMENT

Номер: US20130259800A1
Автор: Deftereos Spyros, Persidis Andreas
Принадлежит: BIOVISTA, INC.

The invention described herein pertains to the use of oxazolidinone antibiotics, alone or in combination, in the treatment of cancer. In particular, the invention pertains to the treatment of malignant gliomas, thyroid cancer or melanoma, or borderline forms of malignant glioma, thyroid cancer or melanoma. 1. A method for treating a patient with malignant glioma , thyroid cancer or melanoma , the method comprising the step of administering to the patient a therapeutically effective amount of an oxazolidinone antibiotic , or a pharmaceutically acceptable salt thereof.23.-. (canceled)6. The method of wherein Ris a group (CH)N(R)COR claim 4 , a group (CH)OH or a group (CH)ORwherein n is 1 claim 4 , 2 or 3 claim 4 , and Rand Rare independently selected from hydrogen and (C-C) hydrocarbyl optionally substituted with one or more hydroxy claim 4 , fluorine or chlorine groups and Ris a C-linked 5-membered heteroaryl ring containing 2 to 4 heteroatoms independently selected from N claim 4 , O and S claim 4 , which ring is optionally substituted on an available carbon atom by 1 or 2 substituents independently selected from (C-C) alkyl claim 4 , amino claim 4 , (C-C) alkylamino claim 4 , (C-C) alkoxy and halo claim 4 , and/or on an available nitrogen atom claim 4 , provided the ring is not thereby quaternized claim 4 , by (C-C) alkyl.7. The method of wherein the oxazolidinone antibiotic is (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl-2-oxo-5-oxazolidinyl]methyl]acetamide claim 1 , N-[(5S)-[3-[[3-fluoro-4-[4-(2-fluoroethyl)-3-oxopiperazin-1-yl]phenyl]-2-oxooxazolidin-5-yl]methyl]acetamide claim 1 , N-[[(5S)-3-[4-(1 claim 1 ,1-dioxido-4-thiomorpholinyl)-3 claim 1 ,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide claim 1 , (S)-N-[[3-[5-(4-pyridyl)pyrid-2-yl]-2-oxo-5-oxazolidinyl]methyl]acetamide claim 1 , or (S)-N-[[3-[5-(3-pyridyl)thiophen-2-yl]-2-oxo-5-oxazolidinyl]methyl]acetamide claim 1 , or a pharmaceutically acceptable salt of the foregoing.8. (canceled)13. The ...

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Номер записи: 19
17-10-2013 дата публикации

INHIBITORS FOR ANTIVIRAL USE

Номер: US20130274267A1
Автор: Baker Jonathan Alleman, Cesar Castro Palomino Laria Julio, Guibourt Nathalie, Muñoz Alberto Ortega
Принадлежит:

The present invention relates to the use of potent selective LSD1 inhibitors and LSD1/MAO-B iithibitors for treating or preventing viral infections. Furthermore, the present invention relates to the new use of cyclopropylamine acetamide derivatives or cyclopropylamine derivatives, as defmed herein, for treating or preventing viral infection and treating or preventing reacti - vation of a virus after latency. 1. A method of treating a viral infection , the method comprising administering to a host a therapeutically effective amount of a selective potent LSD1 inhibitor or a LSD1/MAO-B dual inhibitor , or a pharmaceutically acceptable salt thereof.2. A method of treating or inhibiting reactivation of a virus after latency in a host , the method comprising administering a therapeutically effective amount of a potent LSD1 inhibitor or a LSD1/MAO-B dual inhibitor , or a pharmaceutically acceptable salt thereof.3. A method of treating a viral infection in a mammal that has undergone , is undergoing , or will undergo an organ or tissue transplant , the method comprising administering a therapeutically effective amount of a potent LSD1 inhibitor or a LSD1/MAO-B dual inhibitor , or a pharmaceutically acceptable salt thereof.43. The method according to any one of , , and , wherein the potent LSD1 inhibitor or LSD1/MAO-B dual inhibitor is a cyclopropylamine acetamide derivative or a cyclopropylamine derivative.56-. (canceled)7. The method according to any one of and , wherein the host is a mammal.8. The method according to claim 7 , wherein the mammal is a human.93. The method according to any one of claim 7 , claim 7 , and claim 7 , wherein the viral infection is caused by herpesvirus claim 7 , adenovirus claim 7 , human papilloma virus claim 7 , parvovirus B19 claim 7 , smallpox virus claim 7 , vaccinia virus claim 7 , hepatitis B virus claim 7 , polyoma virus claim 7 , JC virus claim 7 , or transfusion transmitted virus.103. The method according to any one of claim 7 , claim ...

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Номер записи: 20
24-10-2013 дата публикации

HYDROCHLORIDE SALTS OF 8-[1-(3,5-BIS-(TRIFLUOROMETHYL)PHENYL)-ETHOXYMETHYL]-8-PHENYL-1,7-DIAZASPIRO[4,5]DECAN-2-ONE AND PREPARATION PROCESS THEREFOR

Номер: US20130281477A1
Автор: Guenter Frank Bruno, Hu Mengwei, Mergelsberg Ingrid, Paliwal Sunil, Shih Neng-Yang
Принадлежит:

Disclosed are hydrochloride and tosylate crystalline salt forms of (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one, represented by Formula I and methods of preparing the same. 2) The Form I hydrochloride salt form of yielding an x-ray powder diffraction pattern having additional characteristic peaks present at diffraction angles (in 2 θ) of: 12.9 (S); 15.4 (S); 17.3 (S); 20.2 (S).5) A crystalline Form II Tosylate salt form of (5S claim 1 ,8S)-8-[{(1R)-1-(3 claim 1 ,5-Bis-(trifluoromethyl)phenyl)-ethoxy]-methyl}-8-phenyl-1 claim 1 ,7-diazaspiro[4.5]decan-2-one characterized by an x-ray powder diffraction pattern having peaks present at diffraction angles (in 2 θ) of: 5.0 (VS); 10.0 (S); 13.6 (M); and 19.7 (VS).6) A crystalline Form III Tosylate salt form of (5S claim 1 ,8S)-8-[{(1R)-1-(3 claim 1 ,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1 claim 1 ,7-diazaspiro[4.5]decan-2-one which is characterized by an x-ray powder diffraction pattern having peaks present at diffraction angles (in 2 θ) of: 6.3 (M); 9.7 (VS); 20.2 (S); and 22.2 (S).7) A crystalline Form IV Tosylate salt form of (5S claim 1 ,8S)-8-[{(1R)-1-(3 claim 1 ,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1 claim 1 ,7-diazaspiro[4.5]decan-2-one which is characterized by an x-ray powder diffraction pattern having peaks present at diffraction angles (in 2 θ) of: 6.1 (S); 9.6 (S); 20.9 (S); and 22.0 (S).9) A pharmaceutical composition comprising the crystalline salt of and a pharmaceutically acceptable carrier and optionally one or more additional therapeutic agents.10) A combination comprising the composition of and a chemotherapeutic agent.11) The combination of wherein the chemotherapeutic agent is temozolomide.12) A pharmaceutical composition comprising the crystalline salt of and a pharmaceutically acceptable carrier optionally in combination with one or more additional therapeutic agents.13) A pharmaceutical composition ...

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Номер записи: 21
07-11-2013 дата публикации

Combination Therapy for Cancer

Номер: US20130296407A1
Автор: Maatta Ann-Marie, Pikkarainen Jere, Samaranayake Haritha, Yla-Herttuala Seppo
Принадлежит: Ark Therapeutics, Ltd.

An agent comprises a vector having a functional gene, a prodrug which can be converted into a cytotoxic agent by an expression product of the gene, and another cytotoxic agent, as a combined preparation for simultaneous, sequential or separate use in the therapy of cancer or of a disease characterised by an impaired mismatch repair (MMR) pathway, wherein the dosage regimen comprises beginning another cytotoxic agent therapy no later than 7 days after the prodrug therapy has finished. 1. A method of treating glioblastoma multiforme , said method comprising the steps of:a. Diagnosing in a human patient glioblastoma multiforme;b. Identifying in said patient at least one glioblastoma multiforme tumor;c. Resectioning said glioblastoma multiforme tumor to remove at least part of said glioblastoma multiforme tumor and expose tumor bed tissue;d. Administering to said tumor bed tissue an AdHSV-tk adenoviral vector having a gene coding for thymidine kinase, whereby said AdHSV-tk adenoviral vector transfects said tumor bed tissue and said tumor bed tissue expresses said gene coding for thymidine kinase;e. Within about 5 to about 19 days after administering said adenoviral vector to said human patient, further administering to said human patient ganciclovir;f. Administering to said human patient temozolomide per os or by intravenous infusion.2. The method of claim 1 , wherein said glioblastoma multiforme is recurrent glioblastoma multiforme.3. The method of claim 1 , wherein said temozolamide is administered in a plurality of 28-day cycles claim 1 , each cycle comprising administration of a dose of about 150 mg/mper day each day for days 1-5 of said 28-day cycle claim 1 , followed by a dose of about 0 mg/mper day for days 6-28 of said 28-day cycle.4. The method of claim 3 , wherein said plurality of 28-day cycles is preceded by period of about 42 days wherein temozolamide is administered at a dosage of about 75 mg/mper day.5. The method of claim 1 , wherein said AdHSV-tk ...

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Номер записи: 22
14-11-2013 дата публикации

METHODS FOR TREATING CHRONIC PELVIC PAIN SYNDROME WITH ANTIBODIES THAT BINDS MCP-1 OR MIP-1A

Номер: US20130303530A1
Автор: Klumpp David, Schaeffer Anthony J., Thumbikat Praveen
Принадлежит: Northwestern University

The present invention provides methods and compositions for treating chronic pelvic pain syndrome. In particular, the present invention provides methods and compositions for treating chronic pelvic pain syndrome with an agent that targets MCP-1, MIP-1α, or the CCR-2 receptor. 1. A method of treating a subject having , or suspected of having , chronic pelvic pain syndrome comprising:treating a subject with an agent that targets MCP-1, MIP-1α, or the CCR-2 receptor,wherein said subject has one or more symptoms of chronic pelvic pain syndrome,wherein said agent is selected from the group consisting of: an indolopiperidine, a spiropiperidine, a 2-substituted indole, a pyrazolone derivative, a 2-substituted benzimidazole, an N,N-dialkylhomopiperazine, a bicyclic pyrrole, a 5-aryl pentadienamide, and a cyclic amine derivative; andwherein said treating is under conditions such that at least one of said symptoms is reduced or eliminated.2. A method of diagnosing and treating chronic pelvic pain syndrome comprising:a) detecting the expression of MCP-1 and/or MIP-1α in said sample from a subject, wherein said subject has one or more symptoms of chronic pelvic pain syndrome; andb) treating said subject with an agent that targets MCP-1, MIP-1α, the CCR-2 receptor, wherein said treating is under conditions such that at least one of said symptoms is reduced or eliminated, and wherein said agent is selected from the group consisting of: an indolopiperidine, a spiropiperidine, a 2-substituted indole, a pyrazolone derivative, a 2-substituted benzimidazole, an N,N-dialkylhomopiperazine, a bicyclic pyrrole, a 5-aryl pentadienamide, and a cyclic amine derivative.3. The method of claim 2 , wherein said chronic pelvic pain syndrome is non-inflammatory chronic pelvic pain syndrome.4. The method of claim 2 , wherein said subject is male claim 2 , and wherein said sample comprises an expressed prostatic secretion sample from said subject.5. The method of claim 4 , wherein said expressed ...

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Номер записи: 23
14-11-2013 дата публикации

NON-SEDATING ANTIHISTAMINE INJECTION FORMULATIONS AND METHODS OF USE THEREOF

Номер: US20130303546A1
Автор: Du Jie
Принадлежит: JDP THERAPEUTICS, INC.

Described herein are injectable compositions containing non-sedating or second and third generation antihistamines such as cetirizine/levocetirizine and methods of use thereof. Specifically, methods of treating acute urticaria or angioedema associated with an acute allergic reaction are disclosed. In certain embodiments, the injectable compositions are bioequivalent to currently marketed oral dosage forms with the same number of mg of cetirizine. 1. A method of treating a patient in need of injection with cetirizine , comprising , comprisingadministering to the patient an intramuscular injection of an injectable cetirizine composition containing 2 mg to 20 mg of cetirizine,wherein at least about 5 ng/mL of cetirizine appears in the patient's bloodstream within about 4 minutes of administration.2. The method of claim 1 , wherein the patient is in need of treatment for acute urticaria or angioedema associated with an acute allergic reaction claim 1 , wherein the acute allergic reaction optionally includes anaphylaxis.3. The method of claim 1 , wherein it is not feasible to administer oral cetirizine to the patient. This application is divisional of U.S. application Ser. No. 13/238,453 filed on Sep. 21, 2011, which is a continuation in part of U.S. application Ser. No. 12/829,857 filed on Jul. 2, 2010, now U.S. Pat. No. 8,314,083 issued Nov. 20, 2012, which is a continuation in part of U.S. application Ser. No. 12/704,089 filed on Feb. 11, 2010, now U.S. Pat. No. 8,263,581 issued Sep. 11, 2012, which is a nonprovisional of U.S. Provisional Application Ser. Nos. 61/248,441 filed Oct. 3, 2009 and 61/222,951 filed Jul. 3, 2009, all which are hereby incorporated by reference in their entirety.Acute allergic reaction, ranging from the milder cases of acute urticaria to the most severe cases of anaphylaxis, is a systemic, immediate hypersensitivity reaction caused by exposure to a specific antigen. The immune system activates immunoglobulin E (IgE), which reacts with ...

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Номер записи: 24
28-11-2013 дата публикации

METHOD OF TREATING ATRIAL FIBRILLATION

Номер: US20130317038A1
Автор: Antzelevitch Charles, Belardinelli Luiz, Burashnikov Alexander, Shryock John, Zeng Dewan
Принадлежит: Gilead Sciences, Inc.

The present invention relates to a method for the treatment or prevention of atrial fibrillation and/or atrial flutter comprising coadministration of a synergistically therapeutic amount of dronedarone or a pharmaceutically acceptable salt or salts thereof and a synergistically therapeutic amount of ranolazine or a pharmaceutically acceptable salt or salts thereof. Also provided are methods for modulating ventricular and atrial rhythm and rate. This invention also relates to pharmaceutical formulations that are suitable for such combined administration. 133-. (canceled)34. A pharmaceutical formulation comprising dronedarone or a pharmaceutically acceptable salt thereof , ranolazine , and a pharmaceutically acceptable carrier or diluent.35. The formulation of claim 34 , formulated for intravenous administration.36. The formulation of claim 35 , formulated for oral administration.37. The formulation of claim 36 , wherein the formulation is in tablet form.38. The formulation of claim 37 , wherein the tablet comprises from about 10 mg to about of 800 mg of dronedarone or a pharmaceutically acceptable salt thereof.39. The formulation of claim 38 , wherein the tablet comprises from about 25 mg to about 600 mg of dronedarone or a pharmaceutically acceptable salt thereof.40. The formulation of claim 39 , wherein the tablet comprises from about 25 mg to about 400 mg of dronedarone or a pharmaceutically acceptable salt thereof.41. The formulation of claim 40 , wherein the tablet comprises from about 50 mg to about 200 mg of dronedarone or a pharmaceutically acceptable salt thereof.42. The formulation of claim 37 , wherein the tablet comprises from about 50 mg to about 1000 mg of ranolazine.43. The formulation of claim 42 , wherein the tablet comprises from about 100 mg to about 750 mg of ranolazine.44. The formulation of claim 43 , wherein the tablet comprises from about 150 mg to about 375 mg of ranolazine.45. The formulation of claim 37 , wherein the ranolazine is ...

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Номер записи: 25
12-12-2013 дата публикации

Combination Therapy for Cancer

Номер: US20130331442A1
Автор: Maatta Ann-Marie, Pikkarainen Jere, Samaranayake Haritha, Yla-Herttuala Seppo
Принадлежит: FinVector Vision Therapies Ltd

An agent comprises a vector having a functional gene, a prodrug which can be converted into a cytotoxic agent by an expression product of the gene, and another cytotoxic agent, as a combined preparation for simultaneous, sequential or separate use in the therapy of cancer or of a disease characterised by an impaired mismatch repair (MMR) pathway, wherein the dosage regimen comprises beginning another cytotoxic agent therapy no later than 7 days after the prodrug therapy has finished. 1. In a method of treating brain cancer in an immunocompetent human patient by administering temozolomide to said immunocompetent human patient , the improvement comprising: administering to said immunocompetent human patient a viral vector.2. The method of claim 1 , wherein said viral vector is administered in an amount of about 1 to 3×10cfu.3. The method of claim 1 , further comprising: resecting at least part of said brain cancer.4. The method of claim 3 , wherein said resecting forms a cavity and wherein said cavity has a cavity wall claim 3 , and wherein said administration of said viral vector comprises administration to the wall of the cavity formed by the resecting.5. The method of claim 1 , wherein said viral vector comprises virus selected from the group consisting of: lentivirus and adenovirus.6. The method of claim 1 , wherein said viral vector comprises a thymidine kinase transgene claim 1 , and wherein said method of treatment further comprises administering to said human patient ganciclovir or an analogue thereof.7. The method of claim 1 , wherein said brain cancer is selected from the group consisting of: glioblastoma multiforme and anaplastic astrocytoma.8. The method of claim 1 , further comprising administering to said human patient radiotherapy.9. The method of claim 6 , wherein said administration of said ganciclovir or analogue thereof lasts for from about 10 to about 20 days.10. The method of claim 6 , wherein said administration of said temozolomide lasts for not ...

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Номер записи: 26
26-12-2013 дата публикации

METHOD OF USING DIKETOPIPERAZINES AND COMPOSITION CONTAINING THEM

Номер: US20130345238A1
Автор: Bar-Or David, Curtis C. Gerald, Rao Nagaraja K.R., Thomas Greg
Принадлежит: DMI ACQUISITION CORP.

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: 128-. (canceled)30. The composition of wherein Ris —OH or —OR.31. The composition of wherein Ris —OH.32. The composition of wherein Ris —CHCOOH.33. The composition of claim 29 , wherein Ris the side chain of an amino acid selected from the group consisting of glycine claim 29 , alanine claim 29 , valine claim 29 , leucine claim 29 , isoleucine claim 29 , phenylalanine claim 29 , and norvaline.34. The composition of claim 33 , wherein Ris the side chain of alanine.35. The composition of claim 30 , wherein Ris the side chain of an amino acid selected from the group consisting of glycine claim 30 , alanine claim 30 , valine claim 30 , leucine claim 30 , isoleucine claim 30 , phenylalanine claim 30 , and norvaline.36. The composition of claim 35 , wherein Ris the side chain of alanine.37. The composition of claim 31 , wherein Ris the side chain of an amino acid selected from the group consisting of glycine claim 31 , alanine claim 31 , valine claim 31 , leucine claim 31 , isoleucine claim 31 , phenylalanine claim 31 , and norvaline.38. The composition of claim 37 , wherein Ris the side chain of alanine.39. The composition of claim 32 , wherein Ris the side chain of an amino acid selected from the group consisting of glycine claim 32 , alanine claim 32 , valine claim 32 , leucine claim 32 , isoleucine claim 32 , phenylalanine claim 32 , and norvaline.40. The composition of claim 39 , wherein Ris the side chain of alanine.41. A pharmaceutical composition for inhibiting inflammation comprising a ...

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Номер записи: 27
02-01-2014 дата публикации

COMBINATION THERAPY OF A TYPE II ANTI-CD20 ANTIBODY WITH AN ANTI-BCL-2 ACTIVE AGENT

Номер: US20140004104A1
Автор: Friess Thomas, Klein Christian, STREIN PAMELA, Umana Pablo
Принадлежит: Hoffmann-La Roche Inc.

The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and an anti-Bcl-2 active agent for the treatment of a patient suffering from cancer, particularly a CD20-expressing cancer. An aspect of the invention is a composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Another aspect of the invention is a kit comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Yet another aspect of the invention is a method for the treatment of a patient suffering from cancer comprising co-administering, to a patient in need of such treatment, a type II anti-CD20 antibody and an anti-Bcl-2 active agent. 1. A composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent.2. A composition according to claim 1 , wherein said type II anti-CD20 antibody has a ratio of the binding capacities to CD20 on Raji cells (ATCC-No. CCL-86) of said type II anti-CD20 antibody compared to rituximab of 0.3 to 0.63. A composition according to claim 1 , wherein said type II anti-CD20 antibody is a humanized B-Ly1 antibody.4. A composition according to claim 1 , wherein said type II anti-CD20 antibody has increased antibody dependent cellular cytotoxicity (ADCC).5. A composition according to claim 1 , wherein at least 40% of the oligosaccharides of the Fc region of said type II anti-CD20 antibody are non-fucosylated.6. A composition according to claim 1 , wherein said anti-Bcl-2 active agent is selected from the group consisting of Oblimersen claim 1 , SPC-2996 claim 1 , RTA-402 claim 1 , Gossypol claim 1 , AT-101 claim 1 , Obatoclax mesylate claim 1 , A-371191 claim 1 , A-385358 claim 1 , A-438744 claim 1 , ABT-737 claim 1 , AT-101 claim 1 , BL-11 claim 1 , BL-193 claim 1 , GX-15-003 claim 1 , 2-Methoxyantimycin A3 claim 1 , HA-14-1 claim 1 , KF-67544 claim 1 , Purpurogallin claim 1 , TP-TW-37 claim 1 , YC-137 and Z-24.7. A composition according to claim 1 , wherein said anti-Bcl-2 active agent is ...

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Номер записи: 28
13-02-2014 дата публикации

Apparatus and method for cryogranulating a pharmaceutical composition

Номер: US20140044790A1
Автор: Edwin Amoro, Karel Vanackere, Michael A. White
Принадлежит: MANNKIND CORP

Cryogranulation systems with improved dispenser assemblies are provided for use in manufacturing frozen pellets of pharmaceutical substances in a fluid medium. Methods of cryogranulating the pharmaceutical substance in the fluid medium are also provided. In particular embodiments, the dispenser assembly is used with suspensions or slurries of pharmaceutical compositions including biodegradable substances, such as proteins, peptides, and nucleic acids. In certain embodiments, the pharmaceutical substance can be adsorbed to any pharmaceutically acceptable carrier particles suitable for making pharmaceutical powders. In one embodiment, the pharmaceutical carrier can be, for example, diketopiperazine-based microparticles. The dispenser assembly improves the physical characteristics of the cryopellets formed and minimizes product loss during processing.

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Номер записи: 29
13-02-2014 дата публикации

Ophthalmic Formulations Of Cetirizine And Methods Of Use

Номер: US20140045803A1
Автор: Abelson Mark Barry, Chapin Matthew J., Gomes Paul, Minno George, Nice Jackie
Принадлежит:

The present invention provides stable topical formulations of cetirizine that provide a comfortable formulation when instilled in the eye and is effective in the treatment of allergic conjunctivitis and/or allergic conjunctivitis. The invention further provides methods of treating allergic conjunctivitis rhinitis, and/or allergic rhinoconjunctivitis in a subject in need of such treatment by topical application of the cetirizine formulations of the invention directly to the eye. 1. A topical ophthalmic formulation comprising about 0.1% cetirizine (w/v) or a pharmaceutically acceptable salt thereof and about 0.005% fluticasone (w/v).2. The ophthalmic formulation of claim 1 , wherein the fluticasone is present as fluticasone propionate.3. The ophthalmic formulation of claim 1 , wherein the cetirizine is present as cetirizine hydrochloride or dihydrochloride.4. The ophthalmic formulation of claim 1 , further comprising glycerin.5. The ophthalmic formulation of claim 4 , wherein the glycerin is at a concentration of 0.1% to 3% (v/v).6. The ophthalmic formulation of claim 1 , further comprising a preservative.7. The ophthalmic formulation of claim 6 , wherein the preservative is benzalkonium chloride or a derivative thereof claim 6 , or a stabilized claim 6 , oxychloro complex.8. The ophthalmic formulation of claim 7 , wherein the preservative is benzalkonium chloride present in amount ranging from 0.005% to 0.02% (v/v).9. The ophthalmic formulation of claim 1 , wherein the pH of the composition is about 5.0 to 8.0.10. The ophthalmic formulation of claim 1 , wherein the formulation is an aqueous formulation claim 1 , an ointment claim 1 , oil claim 1 , a suspension claim 1 , an emulsion claim 1 , or incorporated in a drug delivery device.11. The ophthalmic formulation of claim 9 , wherein the formulation is in an aqueous formulation.12. The ophthalmic formulation of claim 1 , wherein the cetirizine is in solution and the Fluticasone is in suspension.13. A topical ...

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Номер записи: 30
20-03-2014 дата публикации

MAST CELL MARKERS AND PREVENTION, DIAGNOSIS, AND THERAPY FOR CHRONIC PELVIC PAIN SYNDROME

Номер: US20140079718A1
Автор: Done Joseph, Klumpp David J., Rudick Charles, Schaeffer Anthony J., Thumbikat Praveen
Принадлежит: Northwestern University

The present invention provides compositions and methods for detection, diagnosis, treatment and/or prevention of chronic pelvic pain syndrome. In particular, the present invention provides biomarkers of chronic pelvic pain syndrome (e.g., mast cell markers (e.g., tryptase)), and/or inhibition of mast cell function (e.g. inhibition of MCP-1 and/or MIP-1α) to treat or prevent chronic pelvic pain syndrome. 1. A method for treating and/or preventing chronic pelvic pain syndrome in a subject , comprising administering therapeutic composition comprising a therapeutically effective amount of an inhibitor of mast cell function to said subject.2. The method of claim 1 , wherein said inhibitor of mast cell function comprises a combination of a mast cell stabilizer and a histamine receptor antagonist.3. The method of claim 2 , wherein said therapeutic composition further comprising one or more inhibitors of MCP-1 and/or MIP-1α.4. The method of claim 2 , wherein said histamine receptor antagonist comprises a histamine receptor 1 antagonist and/or histamine receptor 2 antagonist.5. A method for treating and/or preventing chronic pelvic pain syndrome in a subject claim 2 , comprising co-administering a mast cell stabilizer and a histamine receptor antagonist.6. The method of claim 5 , further comprising administering one or more inhibitors of MCP-1 or MIP-1α.7. A composition for the treatment or prevention of CPPS claim 5 , comprising:a) a mast cell stabilizer; andb) a histamine receptor antagonist.8. The composition of claim 7 , further comprising an inhibitor of a CPPS biomarker.9. The composition for the treatment or prevention of CPPS of claim 7 , wherein said histamine receptor antagonist comprises a histamine receptor 1 antagonist and/or a a histamine receptor 2 antagonist.10. The composition for the treatment or prevention of CPPS of claim 7 , comprising inhibitors of MIP-1α and/or MCP-1.11. A method for detecting chronic pelvic pain syndrome in a subject claim 7 , ...

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Номер записи: 31
20-03-2014 дата публикации

PHARMACEUTICAL PREPARATIONS CONTAINING HIGHLY VOLATILE SILICONES

Номер: US20140079791A1
Автор: Fazekas Patrik, Mikulásik Endre
Принадлежит: EGIS Pharmaceuticals Public Limited Company

The subject of the present invention is a transdermal preparation containing pharmaceutically active ingredient, wherein the particles of the active ingredient are coated with highly volatile silicones or a mixture thereof, and these coated particles are dispersed in a gel or cream base. The volatile silicone component is hexamethyldisiloxane and/or octamethyltrisiloxane and/or decamethylpentacyclo-siloxane. A further subject of the present invention is a method for the preparation of such pharmaceutical compositions. 1. A transdermal preparation containing a pharmaceutically active ingredient , wherein the particles of the active ingredient are coated with highly volatile silicones or a mixture thereof , and these coated particles are dispersed in a gel or cream base.2. A composition according to claim 1 , characterized in that the active ingredient is acyclovir claim 1 , piroxicam claim 1 , meloxicam claim 1 , ibuprofen claim 1 , diclofenac sodium or diclofenac potassium claim 1 , clotrimazole claim 1 , bifonazole claim 1 , metronidazole claim 1 , nifedipine claim 1 , glycerol trinitrate or cetirizine.3. A composition according to claim 1 , characterized in that the volatile silicone component is hexamethyldisiloxane and/or octamethyltrisiloxane and/or decamethylpentacyclosiloxane.4. A composition according to claim 1 , characterized in that the cream base is carboxyvinyl polymer claim 1 , hydroxypropyl-methylcellulose or mixtures thereof.5. A process for the preparation of the composition according to claim 1 , characterized in that the particles of the active ingredient are coated with highly volatile silicones or a mixture thereof and the obtained mixture is distributed in a gel or cream base claim 1 , thus the particles in the gel or cream base are surrounded with silicone coating. This application claims priority to U.S. patent application Ser. No. 12/672,696, filed Apr. 9, 2010, which claims priority to PCT Application, PCT/HU2008/000083, filed Jul. 10, 2008 ...

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Номер записи: 32
27-03-2014 дата публикации

PROCESS OF MAKING AND USING PHARMACEUTICAL FORMULATIONS OF ANTINEOPLASTIC AGENTS

Номер: US20140088166A1
Автор: Ihnat Peter M., Radhakrishnan Vinay, Ugwu Sydney, Witchey-Lakshmanan Lenore C.
Принадлежит:

In its several embodiments, this invention discloses a pharmaceutical formulation comprising at least one antineoplastic agent or a pharmaceutically acceptable salt thereof, and at least one dissolution enhancing agent sufficient to substantially dissolve said at least one antineoplastic agent in at least one aqueous diluent, wherein said dissolution enhancing agent is urea, L-histidine, L-threonine, L-asparagine, L-serine, L-glutamine or mixtures thereof; a lyophilized powder comprising said pharmaceutical formulation, and articles of manufacture thereof. 1. A process of making a pharmaceutical formulation comprising the steps of:(i) dissolving at least one dissolution enhancing agent in at least one aqueous diluent wherein said dissolution enhancing agent is selected from the group consisting of urea, L-histidine, L-threonine, L-asparagine, L-serine, and L-glutamine; and(ii) adding at least one antineoplastic agent or a pharmaceutically acceptable salt thereof.2. The process according to further comprising:a) adding at least one bulking agent;b) adding at least one buffer;c) adding at least one pH adjuster to form a solution; andd) filtering said solution.3. The process according to claim 2 , further comprising lyophilizing said solution from step (d) to form a lyophilized powder.4. The lyophilized powder claim 3 , produced by the process of .5. An article of manufacture comprising a container containing the lyophilized powder of .6. The article of manufacture according to claim 5 , wherein said container is a syringe or vial.7. The article of manufacture according to claim 5 , further comprising a volume of at least one aqueous diluent suitable for reconstitution of said lyophilized powder.8. A pharmaceutical formulation suitable for administration to a patient claim 4 , said formulation prepared by reconstituting the lyophilized powder of in a volume of at least one aqueous diluent.9. A process for treating or preventing disease in a patient comprising ...

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Номер записи: 33
02-01-2020 дата публикации

TREATMENT OF JOINT CONDITIONS

Номер: US20200000800A1
Автор: Bar-Or David
Принадлежит:

The invention provides a method of treating a joint condition. The method comprises administering a multi-dose regimen of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a method of treating osteoarthritis with multiple doses of a low-molecular weight fraction of human serum albumin. 133.-. (canceled)34. A method of treating a joint disease comprising administering to an animal in need thereof an effective amount of a pharmaceutical composition comprising DA-DKP prepared by removing albumin from a solution of a human serum albumin composition in a multi-dose regimen , wherein the composition is administered once every three months and wherein the number of doses is from 2 to 10 doses.35. The method of claim 34 , wherein the joint disease is a degenerative joint disease.36. The method of claim 35 , wherein the degenerative joint disease is osteoarthritis.37. The method of claim 34 , wherein the composition administered by intra-articular injection is a composition having a concentration of DA-DKP from about 50 μM to about 350 μM.38. The method of claim 34 , wherein the composition further comprises N-acetyl-tryptophan (NAT) claim 34 , caprylic acid claim 34 , caprylate or combinations thereof.39. The method of claim 38 , wherein the composition is a composition having a concentration of NAT claim 38 , caprylic acid claim 38 , caprylate or combinations thereof from about 4 mM to about 20 mM.40. The method of claim 34 , wherein the step of removing the albumin comprises treating the human serum albumin composition by a separation method selected from the group consisting of ultrafiltration claim 34 , sucrose gradient centrifugation claim 34 , chromatography claim 34 , salt precipitation claim 34 , and sonication.41. The method of claim 40 , wherein the step of removing comprises passing the human serum albumin composition over an ultrafiltration membrane with a ...

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Номер записи: 34
04-01-2018 дата публикации

Dosing Regimens for Fast Onset of Antidepressant Effect

Номер: US20180000815A1
Автор: Bang-Andersen Benny, Morillo Connie Sanchez, Søby Karina Krøjer
Принадлежит:

A dose regimes comprising the simultaneous administration of two pharmaceutical compositions, wherein the first pharmaceutical composition is a composition comprising vortioxetine or a pharmaceutically acceptable salt thereof for once daily oral administration, and the second pharmaceutical composition is a composition comprising vortioxetine or a pharmaceutically acceptable salt thereof which together with said first composition quickly achieves a steady-state plasma level of vortioxetine in said patient which steady-state plasma level is the same as the steady-state vortioxetine plasma level achieved by the administration to said patient of said first composition alone. 1. A method for the treatment of depression , said method comprising:simultaneously administering two pharmaceutical compositions to a patient in need thereof,wherein the first pharmaceutical composition is a composition comprising vortioxetine or a pharmaceutically acceptable salt thereof for once daily oral administration, and the second pharmaceutical composition is a composition comprising vortioxetine or a pharmaceutically acceptable salt thereof which, together with said first composition, achieves a steady-state plasma level of vortioxetine in said patient within 36 hours from said simultaneous administration, which steady-state plasma level is essentially the same as the steady-state vortioxetine plasma level achieved by the administration to said patient of said first composition alone.2. The method of claim 1 , wherein said first pharmaceutical composition comprises 5 mg-20 mg vortioxetine or a pharmaceutically acceptable salt thereof claim 1 , and the second pharmaceutical composition is a composition comprising vortioxetine or a pharmaceutically acceptable salt thereof which claim 1 , together with said first composition claim 1 , achieves a steady-state plasma level between 68 ng h/ml and 1625 ng h/ml vortioxetine in said patient within 24 hours from said simultaneous administration.3. ...

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Номер записи: 35
03-01-2019 дата публикации

THERAPEUTIC USES OF 1-[2-(2,4-DIMETHYL-PHENYLSULFANYL)PHENYL]PIPERAZINE

Номер: US20190000836A1
Автор: DRAGHEIM Marianne, FLOREA Ioana
Принадлежит:

The invention provides new therapeutic uses of 1-[2-(2,4-dimethyl-phenylsulfanyl)phenyl]-piperazine and pharmaceutically acceptable salts thereof. 1. 1-[2-(2 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof for use in the long-term treatment of a CNS disease in a patient , wherein said treatment is associated with little or no weight gain.2. 1-[2-(2 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof for use in the treatment of a CNS disease in a patient who has previously received medication (or is still receiving it) for the treatment of said disease which medication was ceased (or has to be ceased) due to weight related adverse events.3. 1-[2-(2 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof use in the treatment of a CNS disease in a patient who is overweight.4. 1-2-(2 claim 3 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof according to claim 3 , wherein said patient is characterised by a BMI above 25.5. 1-[2-(2 claim 3 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof for use in the treatment of a CNS disease in a patient who also suffers from a disease where weight increase should be avoided.6. 1-[2-(2 claim 5 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof according to claim 5 , wherein said patient also suffers from type II diabetes claim 5 , hypertension or coronary heart diseases claim 5 , or is abstaining from nicotine.7. 1-[2-(2 claim 5 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof according to any of - claim 5 , wherein said CNS disease is selected from depression claim 5 , anxiety claim 5 , chronic pain and abuse.8. 1-[2-(2 claim 5 ,4-dimethyl-phenylsulfanyl)phenyl]piperazine and pharmaceutically acceptable salts thereof according to any of - which is the ...

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Номер записи: 36
02-01-2020 дата публикации

METHODS FOR TREATING CENTRAL NERVOUS SYSTEM DISORDERS USING VDAC INHIBITORS

Номер: US20200000801A1
Автор: LEV GRUZMAN Arie, SHOSHAN-BARMATZ Varda
Принадлежит:

The present invention relates to use of small organic compounds interacting with the Voltage-Dependent Anion Channel (VDAC) for the treatment of diseases associated with central nervous system (CNS) disorders, including psychotic disorders, mood disorders, neurodegenerative diseases. In particular the present invention relates to the use of substituted piperazine- and piperidine-derivatives and pharmaceutical compositions comprising same for the treatment of psychotic disorders including schizophrenia, mood disorders, and neurodegenerative diseases. 2. The method of claim 1 , wherein A is nitrogen (N) claim 1 , and said linking group Lis selected from the group consisting of a C-alkylamidylene and a pyrrolidinylene claim 1 , said linking group optionally substituted with one or two of alkyl claim 1 , hydroxy claim 1 , oxo or thioxo group.3. The method of claim 2 , wherein Lis selected from the group consisting of butanamidylene claim 2 , N-methylbutanamidylene claim 2 , N claim 2 ,N-dimethylbutanamidylene claim 2 , 4-hydroxybutanamidylene claim 2 , 4-oxobutanamidylene claim 2 , 4-hydroxy-N-methylbutanamidylene claim 2 , 4-oxo-N-methylbutanamidylene claim 2 , 2-pyrrolidonyl claim 2 , pyrrolidine-2 claim 2 ,5-dionylene claim 2 , 5-thioxo-2-pyrrolidinonylene and 5-methoxy-2-pyrrolidinonylene.4. The method of claim 3 , wherein when Lis butanamidylene claim 3 , N-methylbutanamidylene claim 3 , N claim 3 ,N-dimethylbutanamidylene claim 3 , 4-hydroxybutanamidylene claim 3 , 4-oxobutanamidylene claim 3 , 4-hydroxy-N-methylbutanamidylene or 4-oxo-N-methylbutanamidylene claim 3 , the carbon (C) in third position of the butanamide moiety is bonded to the nitrogen (N) of the piperazine ring and the nitrogen (N) of the butanamide moiety is bonded to R; or wherein when Lis 2-pyrrolidone claim 3 , pyrrolidine-2 claim 3 ,5-dione claim 3 , 5-thioxo-2-pyrrolidone or 5-methoxy-2-pyrrolidone claim 3 , a carbon (C) of the pyrrolidine moiety is bonded to the nitrogen (N) of the ...

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Номер записи: 37
03-01-2019 дата публикации

Process For Production of Ketones From Secondary Alcohols

Номер: US20190002384A1
Автор: Cabral Da Conceicao Jose Luis, Correia Carabineiro Sonia Alexandra, Da Costa Ribeiro Ana Paula, Dias R. De Sousa Martins Luisa Margarida, L. De Oliveira Pombeiro Armando Jose
Принадлежит:

The present invention relates to the process for production of ketones from secondary alcohols by the use of a hybrid material, formed by the dichlorohydrotris(pyrazol-1-yl)methane iron (II) complex covalently bound to multi-walled carbon nanotubes functionalized with superficial carboxylate groups, as efficient and selective catalyst of peroxidative oxidation, microwave-assisted and without solvent addition. 1. A process for production of ketones from secondary alcohols , assisted by microwave radiation comprising the mixture of an oxidising agent with a hybrid , material dichlorohydrotris (pyrazol-1-yl) methane iron (II) covalently bound to multi-walled carbon nanotubes functionalized with superficial carboxylate groups as catalyst , at a temperature of 80° C.2. The process according to claim 1 , wherein the oxidising agent is a 70% aqueous solution of tert-butyl hydroperoxide.3. The process according to claim 1 , wherein the dichlorohydrotris (pyrazol-1-yl) methane iron (II) complex contains an iron content of 2% (w/w).4. The process according to claim 1 , wherein the secondary alcohols are selected from: cyclohexanol claim 1 , 1-phenylethanol claim 1 , o- claim 1 , m- or p-cresols claim 1 , linear alcohols such as 2-hexanol claim 1 , 3-hexanol claim 1 , 1-butanol or 2-butanol claim 1 , and diols claim 1 , among others.5. The process according to claim 1 , wherein the reaction time is one hour.6. The process according to claim 1 , which is free from solvent addition.7. The process according to claim 1 , wherein the catalyst dichlorohydrotris (pyrazol-1-yl) methane iron (II) covalently bound to multiple wall carbon nanotubes functionalized with superficial carboxylate groups is reusable in at least six subsequent catalytic cycles. The present invention relates to the process for production of ketones from secondary alcohols by the use of a hybrid material, formed by the dichlorohydrotris(pyrazol-1-yl)methane iron (II) complex covalently bound to multi-walled ...

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Номер записи: 38
04-01-2018 дата публикации

Compositions and Methods for Inhibiting Tumor Cells by Inhibiting the Transcription Factor ATF5

Номер: US20180002389A1
Автор: Angelastro James, Greene Lloyd A.
Принадлежит:

The present invention relates to methods for treating and/or preventing tumors and/or promoting apoptosis in a neoplastic cell comprising contacting the neoplastic cell with an cell-penetrating dominant-negative ATF5 (“CP-d/n-ATF5”), wherein the CP-d/n-ATF5 is capable of inhibiting ATF5 function and/or activity. 18-. (canceled)9. A cell-penetrating dominant-negative ATF5 molecule consisting essentially of: (i) a cell-penetrating peptide sequence selected from the group consisting of RQIKIWFQNRRMKWKK (SEQ ID NO: 34) , YGRKKRRQRRR (SEQ ID NO: 40) , and GRKKRRQRRRPPQ (SEQ ID NO: 41); (ii) a dominant-negative ATF5 sequence selected from the group consisting of LEQENAE (SEQ ID NO: 1) , LEKEAEELEQENAE (SEQ ID NO: 2) , LARENEELLEKEAEELEQENAE (SEQ ID NO: 3) , and LEQRAEELARENEELLEKEAEELEQENAE (SEQ ID NO: 4); (iii) an ATF5 leucine zipper sequence selected from the group consisting of LEGECQGLEARNRELKERAESV (SEQ ID NO: 26) , LEGECQGLEARNRELRERAESV (SEQ ID NO: 32) , LEGECQGLEARNRELKERAES (SEQ ID NO: 53) , and LEGECQGLEARNRELRERAES (SEQ ID NO: 54); and optionally (iv) one or more tags for isolation , purification , and/or identification.10. The molecule of claim 9 , wherein the cell-penetrating peptide sequence is RQIKIWFQNRRMKWKK (SEQ ID NO: 34).11. The molecule of claim 9 , wherein the cell-penetrating peptide sequence is YGRKKRRQRRR (SEQ ID NO: 40).12. The molecule of claim 9 , wherein the cell-penetrating peptide sequence is GRKKRRQRRRPPQ (SEQ ID NO: 41).13. The molecule of claim 9 , wherein the dominant-negative ATF5 sequence is LEQENAE (SEQ ID NO: 1).14. The molecule of claim 9 , wherein the dominant-negative ATF5 sequence is LEKEAEELEQENAE (SEQ ID NO: 2).15. The molecule of claim 9 , wherein the dominant-negative ATF5 sequence is LARENEELLEKEAEELEQENAE (SEQ ID NO: 3).16. The molecule of claim 9 , wherein the dominant-negative ATF5 sequence is LEQRAEELARENEELLEKEAEELEQENAE (SEQ ID NO: 4).17. The molecule of claim 9 , wherein the ATF5 leucine zipper sequence is ...

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Номер записи: 39
13-01-2022 дата публикации

PHARMACEUTICAL COMPOSITION COMPRISING HISTONE DEACETYLASE 6 INHIBITORS

Номер: US20220008414A1
Автор: BAE Daekwon, BAEK Ji Yeon, Choi Young II, Ha Nina, KIM Min Cheol, Song Ju Young
Принадлежит:

The present invention relates to a pharmaceutical composition for preventing or treating CMT disease, comprising histone deacetylase 6 inhibitor. The pharmaceutical composition according to the present invention has histone deacetylase 6 (HDAC6) inhibitory activity and thus is effective in preventing or treating CMT disease. 8. The pharmaceutical composition according to claim 1 , wherein the compound represented by Formula I claim 1 , isomers thereof or pharmaceutically acceptable salts thereof inhibit histone deacetylase 6 (HDAC6).9. Use of the compound represented by Formula I according to claim 1 , isomers thereof or pharmaceutically acceptable salts thereof in preparation of a medicament for preventing or treating Charcot-Marie-Tooth (CMT) disease.10. A method for preventing or treating Charcot-Marie-Tooth (CMT) disease claim 1 , comprising a step of administering a therapeutically effective amount of the compound represented by Formula I according to claim 1 , isomers thereof or pharmaceutically acceptable salts thereof into a subject.11. Use of the compound represented by Formula I according to claim 1 , isomers thereof or pharmaceutically acceptable salts thereof for preventing or treating Charcot-Marie-Tooth (CMT) diseases. The present invention relates to a pharmaceutical composition for preventing or treating CMT disease, comprising histone deacetylase 6 (HDAC6) inhibitor as an active ingredient; a method for treating using the histone deacetylase 6 (HDAC6) inhibitor; and a use of histone deacetylase 6 (HDAC6) inhibitor in preparing a drug for preventing or treating CMT disease.Charcot-Marie-Tooth (CMT, hereditary motor and sensory neuropathy: HMSN) disease is the most common type of hereditary peripheral nerve disorder caused by a mutation of proteins which constitute nerves. More than 1,000 mutations have been identified from about 90 genes so far (Timmerman et al., (2014) Genes 5:13-32). Upon the development of Charcot-Marie-Tooth (CMT) disease, a ...

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Номер записи: 40
03-01-2019 дата публикации

MCL-1 AS A THERAPEUTIC TARGET IN SCFFBW7 DEFICIENT NEOPLASM

Номер: US20190002989A1
Автор: Wei Wenyi
Принадлежит: BETH ISRAEL DEACONESS MEDICAL CENTER, INC.

Some embodiments are based on the discovery that proliferative diseases (e.g., neoplastic diseases, for example, tumors or cancers) having an FBW7 mutation or other FBW7 deficiency are sensitive to Mc11 inhibiting agents, but resistant to pro-apoptotic drugs that do not inhibit Mc11. Some embodiments provide methods of treating a proliferative disease based on an assessment of FBW7 expression level or mutation status. Some embodiments provide methods of classifying a hyperproliferative cell or cell population, for example, a malignant cell or cell population based on an assessment of FBW7 expression level or mutation status. Some embodiments provide methods of selecting a treatment regimen for treating a proliferative disease, for example, a malignant disorder, based on an assessment of FBW7 expression level or mutation status. 141-. (canceled)42. A method of treating cancer in a subject , the method comprising administering an agent that directly inhibits MCL-1 to a subject having a cancer characterized by a decreased FBW7 expression level or a FBW7 gene comprising a mutation that results in an inability of FBW7 to degrade MCL-1.43. The method of claim 42 , wherein the cancer is T-cell acute lymphoblastic leukemia (T-ALL) claim 42 , breast cancer claim 42 , pancreatic cancer claim 42 , or colon cancer.44. The method of claim 42 , wherein the agent binds directly to MCL-1.45. The method of claim 42 , wherein the agent is a small molecule or a peptide.46. The method of claim 45 , wherein the peptide is a Mcl-1 BH3 helix Stabilized Alpha-Helix of BCL-2 (SAHB).47. The method of claim 45 , wherein the small molecule is obatoclax claim 45 , apogossypol claim 45 , or sabutoclax.48. The method of claim 42 , wherein the FBW7 gene exhibits a deletion claim 42 , frameshift mutation claim 42 , nonsense mutation claim 42 , or point mutation.49. The method of claim 48 , wherein the point mutation is a G423V mutation claim 48 , a R456C mutation claim 48 , a R456H mutation claim ...

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Номер записи: 41
01-01-2015 дата публикации

MCL-1 AS A THERAPEUTIC TARGET IN SCFFBW7 DEFICIENT NEOPLASM

Номер: US20150005317A9
Автор: Wei Wenyi
Принадлежит: BETH ISRAEL DEACONESS MEDICAL CENTER, INC.

Some embodiments are based on the discovery that proliferative diseases (e.g., neoplastic diseases, for example, tumors or cancers) having an FBW7 mutation or other FBW7 deficiency are sensitive to Mcl1 inhibiting agents, but resistant to pro-apoptotic drugs that do not inhibit Mcl1. Some embodiments provide methods of treating a proliferative disease based on an assessment of FBW7 expression level or mutation status. Some embodiments provide methods of classifying a hyperproliferative cell or cell population, for example, a malignant cell or cell population based on an assessment of FBW7 expression level or mutation status. Some embodiments provide methods of selecting a treatment regimen for treating a proliferative disease, for example, a malignant disorder, based on an assessment of FBW7 expression level or mutation status. 1. A method for treating a proliferative disease comprising(a) obtaining a cell from a subject diagnosed with a proliferative disease if the cell is FBW7 deficient, the subject is indicated to be a candidate for treatment with a drug inhibiting Mcl-1; and/or', 'if the cell is not FBW7 deficient, the subject is not indicated to be a candidate for treatment with a drug inhibiting Mcl-1 and/or the subject is indicated to be a candidate for treatment with a pro-apoptotic drug., '(b) determining whether the cell is FBW7 deficient; wherein'}2. The method of claim 1 , wherein the proliferative disease is a neoplastic disease.3. The method of claim 1 , wherein the proliferative disease is a malignant disease.4. The method of claim 1 , wherein the proliferative disease is a cancer.5. The method of claim 1 , wherein the proliferative disease is a leukemia.6. The method of claim 1 , wherein the proliferative disease is T-ALL.7. The method of claim 1 , wherein the determining whether the cell is FBW7 is deficient comprises assessing the mutation status of the FBW7 gene in the cell; whereinif the cell does not comprise a mutation of the FBW7 gene, then ...

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Номер записи: 42
01-01-2015 дата публикации

1-[2-(2,4-Dimethylphenylsulfanyl)-Phenyl]Piperazine As A Compound With Combined Serotonin Reuptake, 5-HT3 And 5-HT1a Activity For The Treatment Of Cognitive Impairment

Номер: US20150005318A1
Автор: Bang-Andersen Benny, Moore Nicholas, Mork Arne, Stensbol Tine Bryan
Принадлежит:

This disclosure relates to a method of treating a disease selected from the group consisting of Alzheimer's disease, cognitive impairment, and attention deficit hyperactivity disorder (ADHD). The method includes administering a therapeutically effective amount of Compound I or a pharmaceutically acceptable salt thereof to patient in need thereof, in which Compound I is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine. 1. A method of treating a disease selected from the group consisting of Alzheimer's disease , cognitive impairment , and attention deficit hyperactivity disorder (ADHD) , the method comprising administering a therapeutically effective amount of Compound I or a pharmaceutically acceptable salt thereof to patient in need thereof , wherein Compound I is 1-[2-(2 ,4-dimethylphenylsulfanyl)-phenyl]piperazine.2. The method of claim 1 , wherein Compound I or a pharmaceutically acceptable salt thereof is a hydrobromide salt of 1-[2-(2 claim 1 ,4-dimethylphenylsulfanyl)-phenyl]piperazine.3. The method of claim 2 , wherein the hydrobromide salt is characterized by XRPD reflections at 6.89 claim 2 , 9.73 claim 2 , 13.78 and 14.64+/−0.10° 28.4. The method of claim 2 , wherein the hydrobromide salt is characterized by an XRPD as shown in .5. The method of claim 2 , wherein the hydrobromide salt has a particle size distribution corresponding to:D98%: 650-680 μm; D50%: 230-250 μm; and D5%: 40-60 μm;D98%: 370-390 μm; d50%: 100-120 μm; and D5%: 5-15 μm;D98%: 100-125 μm; D50%: 15-25 μm; and D5%: 1-3 μm; orD98%: 50-70 μm; D50%: 3-7 μm; and D5%: 0.5-2 μm.6. The method of claim 1 , wherein the disease is Alzheimer's disease.7. The method of claim 1 , wherein the disease is cognitive impairment.8. The method of claim 1 , wherein the disease is ADHD.9. The method of claim 1 , wherein Compound I or a pharmaceutically acceptable salt thereof is administered at a daily dose of 1-20 mg. This is a continuation of U.S. application Ser. No. 14/242,510, filed Apr. 1, 2014, which ...

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Номер записи: 43
14-01-2021 дата публикации

NANOPARTICLE COMPOSITIONS

Номер: US20210008076A1
Автор: Jackman Robin M., KAHANA Jason A., Raheja Raj
Принадлежит:

Provided herein are nanoparticle compositions comprising modulators of the Bcl-2 family proteins, and pharmaceutically acceptable carriers. 1. A composition comprising nanoparticles , wherein the nanoparticles comprise a modulator of a Bcl-2 family protein; and a pharmaceutically acceptable carrier; wherein the pharmaceutically acceptable carrier comprises albumin.2. The composition of claim 1 , wherein the modulator of the Bcl-2 family protein is a modulator of Bcl-2 claim 1 , Bcl-xL claim 1 , Bcl-w claim 1 , Bcl-b claim 1 , A1 claim 1 , and/or Mcl-1.3. The composition of claim 1 , wherein the modulator of the Bcl-2 family protein is a modulator of Bcl-2 claim 1 , Bcl-xL claim 1 , Bcl-w claim 1 , and/or Mcl-1.4. The composition of claim 1 , wherein the modulator of the Bcl-2 family protein is a modulator of Bcl-2 claim 1 , Bcl-xL claim 1 , and/or Mcl-1.5. The composition of any one of - claim 1 , wherein the nanoparticles have an average diameter of about 1000 nm or less for at least about 15 minutes after nanoparticle formation.6. The composition of any one of - claim 1 , wherein the nanoparticles have an average diameter of about 10 nm or greater for at least about 15 minutes after nanoparticle formation.7. The composition of any one of - claim 1 , the nanoparticles have an average diameter of from about 10 nm to about 1000 nm for at least about 15 minutes after nanoparticle formation.8. The composition of any one of - claim 1 , wherein the nanoparticles have an average diameter of about 1000 nm or less for at least about 2 hours after nanoparticle formation.9. The composition of any one of - claim 1 , wherein the nanoparticles have an average diameter of about 10 nm or greater for at least about 2 hours nanoparticle formation.10. The composition of any one of - claim 1 , the nanoparticles have an average diameter of from about 10 nm to about 1000 nm for at least about 2 hours after nanoparticle formation.11. The composition of any one of - claim 1 , wherein the ...

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Номер записи: 44
09-01-2020 дата публикации

SMALL MOLECULE BAX INHIBITORS AND USES THEREOF

Номер: US20200009132A1
Автор: Amgalan Dulguun, Garner Thomas Peter, Gavathiotis Evripidis, Kirshenbaum Lorrie, Kitsis Richard N., Kopp Felix
Принадлежит:

Compounds, compositions and method of using these compounds are disclosed for treating a disease or disorder in which it is desirable to inhibit BAX, such as a cardiovascular disease or disorder. 2. The method of claim 1 , wherein there is no bond between A and B.5. The method of claim 1 , wherein the one or more compounds is administered in an amount effective to inhibit BAX in a subject.6. The method of claim 1 , wherein the disease or condition is selected from the group consisting of hypoxic cardiomyocytes claim 1 , cardiac ischemia claim 1 , cardiac ischemia-reperfusion injury claim 1 , myocardial infarction claim 1 , myocardial infarction and reperfusion injury claim 1 , chemotherapy-induced cardiotoxicity claim 1 , arteriosclerosis claim 1 , heart failure claim 1 , heart transplantation claim 1 , aneurism claim 1 , chronic pulmonary disease claim 1 , ischemic heart disease claim 1 , hypertension claim 1 , pulmonary hypertension claim 1 , thrombosis claim 1 , cardiomyopathy claim 1 , stroke claim 1 , a neurodegenerative disease or disorder claim 1 , an immunological disorder claim 1 , ischemia claim 1 , ischemia-reperfusion injury claim 1 , infertility claim 1 , a hematological disorder claim 1 , renal hypoxia claim 1 , hepatitis claim 1 , a liver disease claim 1 , a kidney disease claim 1 , an intestinal disease claim 1 , liver ischemia claim 1 , intestinal ischemia claim 1 , asthma claim 1 , AIDS claim 1 , Alzheimer's disease claim 1 , Parkinson's disease claim 1 , Huntington's disease claim 1 , retinitis pigmentosa claim 1 , spinal muscular atrophy claim 1 , cerebellar degeneration claim 1 , amyotrophic lateral sclerosis claim 1 , organ transplant rejection claim 1 , arthritis claim 1 , lupus claim 1 , irritable bowel disease claim 1 , Crohn's disease claim 1 , asthma claim 1 , multiple sclerosis claim 1 , diabetes claim 1 , premature menopause claim 1 , ovarian failure claim 1 , follicular atresia claim 1 , fanconi anemia claim 1 , aplastic anemia claim 1 ...

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Номер записи: 45
08-01-2015 дата публикации

METHODS FOR TREATING ALZHEIMER'S DISEASE BY ADMINISTERING CERTAIN SYNTHETIC COMPOUNDS

Номер: US20150011550A1
Автор: Ma Weiwei
Принадлежит: BEIJING JOEKAI BIOTECHNOLOGY LLC

Use of a synthetic compound selected from the group consisting of JKF-006, JKF-011 and JKF-027 in the preparation of a medicament for treating Alzheimer's disease. 1. A method of treating Alzheimer's disease in a subject , comprising administering to the subject an effective amount of a synthetic compound selected from the group consisting of JKF-006 , JKF-011 and JKF-027.2. The method of claim 1 , wherein the compound is administered to the subject via oral or parental administration.3. A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of a compound for treating Alzheimer's disease selected from the group consisting of JKF-006 claim 1 , JKF-011 and JKF-027 claim 1 , and a pharmaceutically acceptable carrier.4. Use of a synthetic compound selected from the group consisting of JKF-006 claim 1 , JKF-011 and JKF-027 in the preparation of a medicament for treating Alzheimer's disease.5. The use according to claim 4 , wherein the medicament is formulated for oral or parental administration. The present application claims the benefit of International Application PCT/US2012/022646 filed on Jan. 26, 2012.This disclosure relates to treatment of Alzheimer's disease. In particular, the disclosure relates to identification of certain synthetic compounds and use of these compounds for treating Alzheimer's disease.Alzheimer's disease is the most common form of dementia, and is a progressive disease that causes memory loss, confusion, and a decline in functioning. To date there is no cure for the disease, and there is a tremendous need for effective treatment for the disease. A model of Alzheimer's disease (AD) has been reported (Iijima et al., 101 (17): 6623-6628, 2004; Iijima et al., 3(2): e1703, 2008), in which pan-neuronal expression of a secretary form of Aβ42 leads to phenotypes that recapitulate major features of AD clinical symptoms, including age-dependent memory loss, neurodegeneration, and accumulation of Aβ deposits.This disclosure is ...

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Номер записи: 46
08-01-2015 дата публикации

N-PHENYLPIPERAZINE DERIVATIVES THAT ARE ANTAGONISTS OF A1A, A1D ADRENOCEPTORS AND 5-HT1A RECEPTORS FOR THE TREATMENT OF BENIGN PROSTATE HYPERPLASIA, PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME

Номер: US20150011566A1
Автор: Barbosa Do Nascimento Viana Jessica, Chagas Da Silva Fernanda, Chaves Barberato Luana, De Camargo Nascente Luciana, German Noël François, Martins da Silva Cláudia Lúcia, Nunes Lemes Laís Flávia, Oliveira Silva Renata, Soares Romeiro Luís Antônio
Принадлежит:

The present invention provides N-phenylpiperazine derivatives for use as multiple binders and/or antagonists of α1A adrenoceptors, α1D adrenoceptors and 5-HT1A serotonin receptors. These substances are candidates to prototypes for the treatment of benign prostate hyperplasia and lower urinary tract symptoms, and are useful in pharmaceutical compositions. 1. N-phenylpiperazine derivatives with high affinity for α1A/D adrenoceptors and 5-HT1A receptors comprising:a basic nitrogen atom for ionic interaction with the carboxylate group of the aspartate residue (Asp) in TM3 of these receptors; andat least one aromatic ring for hydrophobic and electrostatic interactions with complementary residues in TM2 4, 6 and 7; anda group with a negative charge density at position 2 (onto) to the nitrogen or the N-phenylpiperazine subunit, hydrogen bond acceptor e.g. alkoxides and isosteres.3. α1A/D adrenoceptors and 5-HT1A receptors ligands comprising:a basic nitrogen atom for ionic interaction with the carboxylate group of the aspartate residue (Asp) in TM3 of these receptors; andat least one aromatic ring for hydrophobic and electrostatic interactions with complementary residues in TM2 4, 6 and 7.5. Pharmaceutical composition for the treatment of benign prostatic hyperplasia and lower urinary tract symptoms and prostatic anti-proliferative effect comprising a pharmaceutically acceptable carrier and at least one N-phenylpiperazine derivatives with high affinity for α1A/D adrenoceptors and 5-HT1A receptors comprising:a basic nitrogen atom for ionic interaction with the carboxylate group of the aspartate residue (Asp) in TM3 of these receptors; andat least one aromatic ring for hydrophobic and electrostatic interactions with complementary residues in TM2 4, 6 and 7. N-phenylpiperazine derivatives that are antagonists of α1A, α1D adrenoceptors and 5-HT1A receptors for the treatment of benign prostate hyperplasia, pharmaceutical compositions containing the sameThe present invention is ...

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Номер записи: 47
03-02-2022 дата публикации

USE OF 1-[4-BROMO-5-[1-ETHYL-7-(METHYLAMINO)-2-OXO-1,2-DIHYDRO-1,6-NAPHTHYRIDIN-3-YL]-2-FLUOROPHENYL]-3-PHENYLUREA AND ANALOGS FOR THE TREATMENT OF CANCERS ASSOCIATED WITH GENETIC ABNORMALITIES IN PLATELET DERIVED GROWTH FACTOR RECEPTOR ALPHA

Номер: US20220031678A1
Автор: Flynn Daniel L., Kaufman Michael D., Rosen Oliver, Smith Bryan D.
Принадлежит: DECIPHERA PHARMACEUTICALS, LLC

The present disclosure relates to the use of 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea or 1-(5-(7-amino-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-4-bromo-2-fluorophenyl)-3-phenylurea in the treatment of cancers. Specifically, the disclosure is directed to methods of inhibiting PDGFR kinases and treating cancers and disorders associated with inhibition of PDGFR kinases including lung adenocarcinoma, squamous cell lung cancer, glioblastoma, pediatric glioma, astrocytomas, sarcomas, gastrointestinal stromal tumors, malignant peripheral nerve sheath sarcoma, intimal sarcomas, hypereosinophilic syndrome, idiopathic hypereosinophilic syndrome, chronic eosinophilic leukemia, eosinophilia-associated acute myeloid leukemia, or lymphoblastic T-cell lymphoma. 1. A method of treating a progressive gastrointestinal stromal tumor in a patient that has previously received prior tyrosine kinase inhibitor treatment , comprising administering to the patient in need thereof 150 mg , once or twice daily , of the compound 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1 ,2-dihydro-1 ,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea.2. The method of claim 1 , comprising administering to the patient 150 mg of the compound 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1 claim 1 ,2-dihydro-1 claim 1 ,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea once daily.3. The method of claim 1 , wherein the prior tyrosine kinase inhibitor treatment is one prior tyrosine kinase inhibitor treatment.4. The method of claim 3 , wherein the one prior tyrosine kinase inhibitor treatment is imatinib.5. The method of claim 1 , comprising administering to the patient 150 mg of the compound 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1 claim 1 ,2-dihydro-1 claim 1 ,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea once daily.6. The method of claim 3 , comprising administering to the patient 150 mg of the compound 1-[4-bromo-5-[1-ethyl-7-( ...

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Номер записи: 48
21-01-2016 дата публикации

TREATMENT OF T-CELL MEDIATED DISEASES

Номер: US20160015705A1
Автор: Bar-Or David, Bar-Or Raphael, Shimonkevitz Richard
Принадлежит:

The invention provides a method of treating T-cell mediated diseases and a method of inhibiting the activation of T-cells using certain diketopiperazines. The invention also provides methods of synthesizing diketopiperazines and pharmaceutical compositions comprising certain diketopiperazines. The invention further provides methods of making improved pharmaceutical compositions of proteins and peptides by either increasing or decreasing the content of diketopiperazines in the compositions and the resultant improved pharmaceutical compositions.

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Номер записи: 49
21-01-2016 дата публикации

CRYSTALLINE FORMS OF AN ANTIDEPRESSANT COMPOUND

Номер: US20160015706A1
Автор: Allegrini Pietro, CURZI Marco, DICHIARANTE Elena, GIAFFREDA Stefano Luca, GRAZIOSI Renzo, VLADISKOVIC Chiara
Принадлежит: DIPHARMA FRANCIS S.R.L.

The present invention relates to novel crystalline forms of vortioxetine hydrobromide, in particular three crystalline forms, a process for their preparation, a pharmaceutical composition containing said novel crystalline forms, and a process for the purification of vortioxetine or a salt thereof, comprising the formation of one or more of the novel crystalline forms of vortioxetine hydrobromide described herein.

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Номер записи: 50
21-01-2021 дата публикации

USE OF 1-[4-BROMO-5-[1-ETHYL-7-(METHYLAMINO)-2-OXO-1,2-DIHYDRO-1,6-NAPHTHYRIDIN-3-YL]-2-FLUOROPHENYL]-3-PHENYLUREA AND ANALOGS FOR THE TREATMENT OF CANCERS ASSOCIATED WITH GENETIC ABNORMALITIES IN PLATELET DERIVED GROWTH FACTOR RECEPTOR ALPHA

Номер: US20210015801A1
Автор: Flynn Daniel L., Kaufman Michael D., Rosen Oliver, Smith Bryan D.
Принадлежит:

The present disclosure relates to the use of 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea or 1-(5-(7-amino-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-4-bromo-2-fluorophenyl)-3-phenylurea in the treatment of cancers. Specifically, the disclosure is directed to methods of inhibiting PDGFR kinases and treating cancers and disorders associated with inhibition of PDGFR kinases including lung adenocarcinoma, squamous cell lung cancer, glioblastoma, pediatric glioma, astrocytomas, sarcomas, gastrointestinal stromal tumors, malignant peripheral nerve sheath sarcoma, intimal sarcomas, hypereosinophilic syndrome, idiopathic hypereosinophilic syndrome, chronic eosinophilic leukemia, eosinophilia-associated acute myeloid leukemia, or lymphoblastic T-cell lymphoma. 1. A method of treating a progressive gastrointestinal stromal tumor in a patient that has previously received prior tyrosine kinase inhibitor treatment , comprising administering to the patient in need thereof 150 mg , once or twice daily , of the compound 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1 ,2-dihydro-1 ,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea.2. The method of claim 1 , comprising administering to the patient 150 mg of the compound 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1 claim 1 ,2-dihydro-1 claim 1 ,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea once daily.3. The method of claim 1 , wherein the prior tyrosine kinase inhibitor treatment is one prior tyrosine kinase inhibitor treatment.4. The method of claim 3 , wherein the one prior tyrosine kinase inhibitor treatment is imatinib.5. The method of claim 1 , comprising administering to the patient 150 mg of the compound 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1 claim 1 ,2-dihydro-1 claim 1 ,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea once daily.6. The method of claim 3 , comprising administering to the patient 150 mg of the compound 1-[4-bromo-5-[1-ethyl-7-( ...

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Номер записи: 51
21-01-2021 дата публикации

Total Synthesis Of Prostaglandin J Natural Products and Their Intermediates

Номер: US20210017111A1
Автор: Ahmed Tonia S., GRUBBS Robert H., LI Jiaming, Stoltz Brian M., Xu Chen
Принадлежит:

The present disclosure is directed to methods of preparing prostaglandin J natural products by stereoretentive metatheses reactions and intermediates used in the synthesis of these natural products, including the use of intermediates of Formula (I-A), where Ris defined in the specification 5. The method of claim 4 , wherein the compound of Formula (I-A) or (I-B) has an enantiomeric purity corresponding to that of the compound of Formula (II-A) or (II-B) claim 4 , respectively.6. The method of claim 4 , wherein the organocopper allyl source is derived from the admixture of a copper halide and an allyl Grignard reagent claim 4 , optionally in the presence of an alkyl sulfide and alkali metal halide).7. The method of claim 4 , wherein oxidizing the aldol intermediate to the compound having a structure of Formula (I-A) or (I-B) comprises reacting the aldol intermediate with a sulfonylating agent and a base to form the compound of Formula (I-A) or (I-B).9. The method of claim 8 , wherein the conditions suitable for effecting a retro-Diels Alder reaction comprise treating the compounds of Formula (I-A) and (IB) with a Lewis acid catalyst (e.g. claim 8 , methyl or ethyl aluminum chloride) in the optional presence of an olefin.11. The method of claim 10 , wherein the Z-selective or stereoretentive olefin metathesis catalyst is a Grubbs metathesis catalyst. This application claims priority to U.S. Patent Application No. 62/876,531, filed Jul. 19, 2019, the contents of which are incorporated by reference herein for all purposesThis invention was made with government support under Grant No. GM031332 awarded by the National Institutes of Health. The government has certain rights in the invention.The present disclosure is directed to methods of preparing prostaglandin J natural products by stereoretentive metatheses reactions and intermediates used in the synthesis of these natural products.Δ-prostaglandin J natural products (1-4, ) features a unique cross-conjugated dienone ...

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Номер записи: 52
26-01-2017 дата публикации

TREATMENT OF PARKINSON'S DISEASE THROUGH ARFGAP1 INHIBITION USING SUBSTITUTED PIPERAZINE DERIVATIVES

Номер: US20170020866A1
Автор: McMaster Chris, Poon Pak, Roberge Michel, Zimmerman Carla
Принадлежит:

Methods are provided for the treatment of Parkinson's disease (PD) in patients bearing mutations in the LRRK2 gene. A therapeutically effective amount of piperazine derivative compounds are employed to inhibit the biological activity of ArfGAP1, inhibition that counteracts the deleterious effects of mutations in, or increased expression of, the LRRK2 protein. 1. A method of treating or preventing Parkinson's disease in a patient by administrating a pharmaceutical composition comprising:at least a therapeutically effective amount of an ArfGAP1 inhibitor, the ArfGAP1 inhibitor being selected from a group of substituted piperazine derivative compounds.3. The method of claim 2 , wherein n=1 claim 2 , G1 is 2-pyridine or 2-thiophene claim 2 , and G2 is 4-acetophenone or 4-nitrobenzene.4. The method of claim 2 , wherein n=1 claim 2 , G1 is methyl-substituted butene claim 2 , and G2 is 4-nitrobenzene.5. The method of claim 2 , wherein n=1 claim 2 , G1 is unsaturated bicycloheptene claim 2 , and G2 is 4-nitrobenzene.6. The method of claim 2 , wherein n=0 claim 2 , G1 is indane claim 2 , and G2 is 2-pyridine.7. The method of claim 2 , wherein n=0 claim 2 , G1 is formylcyclohexane carboxylic acid claim 2 , and G2 is 4-nitrobenzene.8. The method of claim 2 , wherein the buffering agent controls a proper acidity level for delivering the ArfGAP inhibitor.11. The ArfGAP1 inhibitor of claim 9 , wherein n=1 claim 9 , G1 is 2-pyridine or 2-thiophene claim 9 , and G2 is 4-acetophenone or 4-nitrobenzene.12. The ArfGAP1 inhibitor of claim 9 , wherein n=1 claim 9 , G1 is methyl-substituted butene claim 9 , and G2 is 4-nitrobenzene.13. The ArfGAP1 inhibitor of claim 9 , wherein n=1 claim 9 , G1 is unsaturated bicycloheptene claim 9 , and G2 is 4-nitrobenzene.14. The ArfGAP1 inhibitor of claim 9 , wherein n=0 claim 9 , G1 is indane claim 9 , and G2 is 2-pyridine.15. The ArfGAP1 inhibitor of claim 9 , wherein n=0 claim 9 , G1 is formylcyclohexane carboxylic acid claim 9 , and G2 is 4- ...

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Номер записи: 53
26-01-2017 дата публикации

Cancer Therapy

Номер: US20170021039A1
Автор: ECKLAND David, FARRIES Timothy
Принадлежит: Trizell Ltd.

The prior art largely suggests that immune competence in a cancer patient would destroy an antigenic viral vector before it transfects host cells with a transgene-rendering therapy futile. We surprisingly found the opposite is true: cancer patients with competent immune systems obtain the most therapeutic benefit from antigenic viral vector, apparently because the antigenic viral vector, apart from transfecting cells with a transgene, induces a humoral immune response, which in turn attacks cells bearing cancer antigen. Our new therapy works particularly well in combination with cytotoxic chemotherapeutic drugs. 1. In a method of treating cancer in a human , the improvement comprising:a. Determining the level of immunity against a viral vector,b. Confirming said human has a measurable level of immunity against said vector, andc. Administering to said human said viral vector.2. The method of claim 1 , wherein said administering to said human said viral vector comprises administering to a cavity created by a resection of said tumor.3. The method of claim 1 , wherein said viral vector comprises adenovirus.4. The method of claim 1 , wherein said viral vector comprises a transgene.5. The method of claim 4 , wherein said transgene comprises nucleic acid sequence coding for thymidine kinase enzyme.6. The method of claim 1 , wherein said cancer comprises glioma.7. The method of claim 1 , further comprising administering to said human patient a cytotoxic chemotherapeutic.8. The method of claim 6 , further comprising administering to said human patient temozolomide.9. In a method of treating cancer in a human claim 6 , the improvement comprising:a. Inducing an immune response against a viral vector, and thenb. Administering to said human said viral vector.10. The method of claim 9 , wherein said administering to said human said viral vector comprises administering to a cavity created by a resection of said tumor.11. The method of claim 9 , wherein said viral vector comprises ...

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Номер записи: 54
25-01-2018 дата публикации

CHEMICAL COMPOUNDS

Номер: US20180021316A1
Автор: "ODONOVAN Daniel Hillebrand", BARLAAM Bernard Christophe, Broo Dan Anders, HUGHES Samantha Jayne, MOSS Thomas Andrew, Nissink Johannes Wilhelmus Maria, SCOTT James Stewart, VARNES Jeffrey Gilbert, WU Dedong, YANG Bin
Принадлежит:

The specification relates to compounds of Formula (I): 2. A compound of Formula (I) claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , as claimed in claim 1 , wherein Q is O.6. A compound according to selected from the group consisting of:3,3-difluoro-N-(2-(4-((1R,3R)-2-isobutyl-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenoxy)ethyl)propan-1-amine;3-fluoro-N-(2-(4-((1R,3R)-2-isobutyl-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenoxy)ethyl)propan-1-amine;N-(2-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenoxy)ethyl)-3,3-difluoropropan-1-amine;N-(2-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenoxy)ethyl)-3-fluoropropan-1-amine;N-(2-(3,5-difluoro-4-((1R,3R)-2-((3-fluorooxetan-3-yl)methyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenoxy)ethyl)-3-fluoropropan-1-amine;N-(2-(3,5-difluoro-4-((1R,3R)-2-((1-fluorocyclopropyl)methyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenoxy)ethyl)-3-fluoropropan-1-amine;3-fluoro-N-(2-((5-((1R,3R)-2-((3-fluorooxetan-3-yl)methyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)-4-methoxypyridin-2-yl)oxy)ethyl)propan-1-amine;3-fluoro-N-(2-(4-((1R,3R)-2-((3-fluorooxetan-3-yl)methyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)-3-methoxyphenoxy)ethyl)propan-1-amine;{'sup': 1', '2, 'N-(3,5-difluoro-4-((1R,3R)-2-((1-fluorocyclopropyl)methyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)-N-(3-fluoropropyl)ethane-1,2-diamine;'}3-((1R,3R)-1-(2,6-difluoro-4-(2-((3-fluoropropyl)amino)ethoxy)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol;3-fluoro-N-(2-(4-((1R,3R)-2-((1-fluorocyclopropyl)methyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)-3-methoxyphenoxy)ethyl)propan-1-amine;N-(2-(4-((1R,3R)-2-(2,2-difluoropropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol- ...

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Номер записи: 55
10-02-2022 дата публикации

COMBINATION MAST CELL INHIBITION FOR TREATMENT OF BPH/LUTS

Номер: US20220040143A1
Автор: Schaeffer Anthony J., Thumbikat Praveen
Принадлежит:

Provided herein are compositions and methods for the treatment of conditions such as benign prostatic hyperplasia (BPH), Lower Urinary Tract Symptoms (LUTS), chronic prostatitis (CP) and/or chronic pelvic pain syndrome (CPPS). In particular, provided herein are combination therapies comprising a mast cell inhibitor and a histamine receptor antagonist. 1. A composition comprising a mast cell stabilizer and a histamine receptor antagonist.2. The composition of for use in a method of treating or preventing a condition selected from benign prostatic hyperplasia claim 1 , chronic prostatitis claim 1 , and chronic pelvic pain syndrome.3. (canceled)4. The composition of claim 1 , wherein the mast cell stabilizer is cromolyn sodium.5. The composition of claim 1 , wherein the histamine receptor antagonist is a histamine receptor 1 antagonist or a histamine receptor 2 antagonist.6. The composition of claim 5 , wherein the composition comprises a histamine receptor 1 antagonist claim 5 , wherein the histamine receptor 1 antagonist is cetirizine.79.-. (canceled)10. A method of treating or preventing a condition selected from benign prostatic hyperplasia (BPH) claim 5 , chronic prostatitis (CP) claim 5 , and chronic pelvic pain syndrome (CPPS) in a subject claim 5 , comprising providing to the subject one or more inhibitors of mast cell function.11. The method of claim 10 , wherein the condition is benign prostatic hyperplasia associated with lower urinary tract symptoms.12. The method of claim 10 , wherein the one or more inhibitors of mast cell function are selected from a mast cell stabilizer claim 10 , a histamine receptor 1 antagonist claim 10 , and a histamine receptor 2 antagonist.13. The method of claim 12 , wherein at least one of the inhibitors of mast cell function is a mast cell stabilizer.14. The method of claim 13 , wherein the mast cell stabilizer is cromolyn sodium.15. The method of claim 12 , wherein at least one of the inhibitors of mast cell function is a ...

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Номер записи: 56
10-02-2022 дата публикации

METHOD FOR TREATMENT OF CYTOKINE RELEASE SYNDROME

Номер: US20220040171A1
Автор: CHANDA Dipanjan, CHOI Eun Jung, JEON Jae-Han, JUNG Hoe-Yune, LEE Heon Jong, LEE In-Kyu
Принадлежит: NovMetaHealth Co., Ltd

A composition for preventing and/or treating cytokine release syndrome and a method of prevention and/or treatment of cytokine release syndrome are disclosed. The composition includes an aryl ethene compound, a pharmaceutically acceptable salt thereof, or a solvate thereof, as an active ingredient. The method includes administering the aryl ethene compound, an isomer, a pharmaceutically acceptable salt thereof, or a solvate thereof, in an effective amount to a subject in need thereof. The cytokine release syndrome may be caused by virulent infection. The administration of the compound reduces the pre-inflammatory cytokine levels in the subject. 5. The method of claim 1 , wherein the cytokine release syndrome is caused by virulent infection.6. The method of claim 1 , wherein the cytokine release syndrome is caused by viral infection.7. The method of claim 1 , wherein the cytokine release syndrome an inflammatory disorder.8. The method of claim 7 , wherein the inflammatory disorder is sepsis.9. The method of claim 7 , wherein the inflammatory disorder is pneumonia.10. The method of claim 1 , wherein the administering the compound reduces pro-inflammatory cytokine level in serum of the subject.11. The method of claim 10 , wherein the pro-inflammatory cytokine is IFNb claim 10 , IL1b claim 10 , TNFα claim 10 , and/or IL6.14. The method of claim 13 , wherein the cytokine release syndrome is induced by viral infection.17. The method of claim 15 , wherein the subject has a virulent infection. This application claims priority to and benefits based on U.S. Provisional Patent application No. 63/060,779 filed Aug. 4, 2020, the content of which is incorporated by reference herein in its entirety.This disclosure includes a method for treatment of cytokine release syndrome. In an aspect, the disclosure concerns the use of a molecule to reduce or prevent exaggerated production of cytokines in macrophage upon virulent infection. This molecule serves to prevent mitochondrial ...

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Номер записи: 57
10-02-2022 дата публикации

METHOD AND COMPOSITION FOR TREATING CORONA VIRUS, INFLUENZA, AND ACUTE RESPIRATORY DISTRESS SYNDROME

Номер: US20220040227A1
Автор: MAGOLSKE Charles, VOELKEL Norbert F.
Принадлежит: ReversPAH LLC

A method of treating a Corona Virus, e.g., COVID 19, Influenza and ARDS, is provided. A copper chelator including a tetrathiomolybdate salt is administered with a 5-lipoxygenase enzyme inhibitor, e.g., Diethylcarbamazine or Zileuton. Baicalin, Bufalin, Quercetin, Curcumin, inhibitors of NF-kappaB, the Applied Therapeutics Aldose Reductase inhibitor AT-001, Sulforaphane or Fluvoxamine can be additional drugs. This is an intervention treatment of a Corona Virus, e.g., COVID 19, ideally in the second phase of the disease, in the Pulmonary Phase, preferably prior to the Hyper-Inflammation Phase, as a preventive therapy to reduce the need for a ventilator and increase the survival of hospitalized patients. The two-drug treatment combination aims at preventing ARDS and other organ damage caused by COVID 19 infection by targeting the intravascular disease component. Tetrathiomolybdate in oral and Intravenous forms combined with the other drugs in intravenous or inhaled forms are designed to treat advanced forms of these diseases. 1. A method of treating a Corona Virus or Influenza in a patient in need thereof , comprising administering to the patient a therapeutically effective amount of a copper chelator comprising a tetrathiomolybdate salt and at least one co-drug , wherein the Corona Virus is COVID-19 , a mutation of COVID 19 , another Corona Virus , or variant(s) with similar mechanisms of action to Covid 19 or Acute Respiratory Distress Syndrome (ARDS).2. The method of claim 1 , wherein the copper chelator comprises a tetrathiomolybdate salt according to:{'br': None, 'sub': '4', 'X(MoS),'}wherein:{'sup': +2', '+2', '+2', '+2', '+2', '+', '1', '2', '3', '4', '+', '5', '6', '7', '8, 'X is (2Li), (2K)(2Na)Mg, Ca, or {[N(R) (R) (R) (R)][N(R) (R) (R) (R)]},'}{'sup': 1', '2', '3', '5', '6', '7, 'R, R, R, R, R, and Rare independently H, or optionally substituted group selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, ...

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Номер записи: 58
26-01-2017 дата публикации

BRIDGED PHTHALOCYANINE- AND NAPTHTHALOCYANINE-METAL COMPLEX CATALYSTS AND METHODS OF USING AND PURIFYING THE SAME

Номер: US20170022233A1
Автор: McGaff Robert William
Принадлежит:

Various embodiments disclosed relate to bridged phthalocyanine- and napththalocyanine-metal complex catalysts and methods of using and purifying the same. In various embodiments, the present invention provides a method of purifying a catalyst. The method includes contacting a catalyst composition with acid, the catalyst composition including a catalyst, to provide an acidified catalyst composition with the catalyst dissolved therein. The method includes precipitating the catalyst, and removing the precipitated catalyst from solution, to provide a purified catalyst. 2. The method of claim 1 , wherein the precipitating comprises at least partially neutralizing the acidified composition.3. The method of claim 1 , wherein the removing comprises washing the precipitated catalyst with water.4. The method of claim 1 , wherein the purified catalyst is about 95 wt % pure to about 100 wt % pure.5. The method of claim 1 , wherein axial ligand L is chosen from MeOH and HO.6. The method of claim 1 , wherein at one more occurrences at least one of R claim 1 , R claim 1 , R claim 1 , and Ris a hydrophilic group claim 1 , wherein at each occurrence claim 1 , the hydrophilic group is chosen from —C(O)OH claim 1 , —O—C(O)OH claim 1 , —P(O)(OH) claim 1 , —OP(O)(OH) claim 1 , —S(O)(O)OH claim 1 , —OS(O)(O)OH claim 1 , a salt thereof claim 1 , a substituted or unsubstituted (C-C)hydrocarbyl ester thereof claim 1 , and a combination thereof.7. The method of claim 1 , wherein at one more occurrences at least one of R claim 1 , R claim 1 , R claim 1 , and Ris —S(O)(O)OH.12. The purified catalyst of claim 11 , wherein axial ligand L is chosen from MeOH and HO.13. The purified catalyst of claim 11 , wherein at each occurrence claim 11 , the hydrophilic group is chosen from —C(O)OH claim 11 , —O—C(O)OH claim 11 , —P(O)(OH) claim 11 , —OP(O)(OH) claim 11 , —S(O)(O)OH claim 11 , —OS(O)(O)OH claim 11 , a salt thereof claim 11 , a substituted or unsubstituted (C-C)hydrocarbyl ester thereof claim ...

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Номер записи: 59
24-01-2019 дата публикации

TREATMENT OF JOINT CONDITIONS

Номер: US20190022087A1
Автор: Bar-Or David
Принадлежит: AMPIO PHARMACEUTICALS, INC.

The invention provides a method of treating a joint condition. The method comprises administering a multi-dose regimen of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a method of treating osteoarthritis with multiple doses of a low-molecular weight fraction of human serum albumin. 1. A method of treating a joint condition comprising administering to an animal with a Kellgren-Lawrence Grade 4 pain score an effective amount of a pharmaceutical composition comprising DA-DKP prepared by removing albumin from a solution of a human serum albumin composition in a multi-dose regimen , wherein the number of doses in the multi-dose regimen is between 2 and 6 doses per 52 weeks.2. The method of claim 1 , wherein the joint condition is a joint disease.3. The method of claim 2 , wherein the joint disease is a degenerative joint disease.4. The method of claim 3 , wherein the degenerative joint disease is osteoarthritis.5. The method of claim 1 , wherein the joint condition is a joint injury.6. The method of claim 5 , wherein the joint injury is at least one of a traumatic injury and a post-operative injury.7. The method of claim 5 , wherein the joint injury is a repetitive strain injury.8. The method of claim 1 , wherein the joint condition is inflammation.9. The method of claim 1 , wherein the composition is administered by an administration route selected from the group consisting of local administration claim 1 , topical administration claim 1 , and injection.10. The method of claim 9 , wherein administration by injection is by intra-articular injection.11. The method of claim 10 , wherein the composition administered by intra-articular injection is a composition having a concentration of DA-DKP from about 50 μM to about 350 μM.12. The method of claim 1 , wherein the composition further comprises N-acetyl-tryptophan (NAT) claim 1 , caprylic acid claim 1 , caprylate or ...

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Номер записи: 60
24-01-2019 дата публикации

USE OF WX-UK1 AND ITS PRODRUG, WX-671, FOR THE TREATMENT OF NON-CANCEROUS MEDICAL CONDITIONS

Номер: US20190022088A1
Автор: Abramson Danielle, Fathi Reza, Levitt Mark, Plasse Terry
Принадлежит:

The present invention relates to methods of treating an animal having a non-cancerous medical condition that is ameliorated by treatment with a trypsin inhibitor, the method comprising obtaining a biological sample from the animal; testing the sample to obtain a trypsin concentration, wherein, if the trypsin concentration is above the upper limit of the normality, the animal is treated for a suitable period of time by administering to the animal a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically-acceptable carrier and the compound N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamidino-phenylalanine-4-ethoxycarbonylpiperazide, the stereoisomers, racemic mixtures, metabolite, pharmaceutically acceptable salt, crystal, or any combination thereof. In an embodiment, the non-cancerous medical condition is an inflammatory digestive disease selected from the group consisting of pancreatitis, gastritis, irritable bowel syndrome, and inflammatory bowel disease. In an embodiment, the pharmaceutical composition is in an orally administrable form. 1. A method comprising:obtaining a biological sample from an animal having a non-cancerous medical condition;testing the sample to obtain a trypsin concentration, wherein, if the trypsin concentration is above the upper limit of the normality, the animal is treated for a suitable period of time by administering to the animal a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically-acceptable carrier and the compound N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamidino-phenylalanine-4-ethoxycarbonylpiperazide, the stereoisomers, racemic mixtures, metabolite, pharmaceutically acceptable salt, crystal, or any combination thereof.2. The method of claim 1 , wherein the biological sample is selected from the group consisting of blood claim 1 , serum claim 1 , urine claim 1 , saliva claim 1 , duodenal fluid and intestinal mucosal biopsies.3. The method ...

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Номер записи: 61
22-01-2015 дата публикации

PROCASPASE COMBINATION THERAPY FOR GLIOBLASTOMA

Номер: US20150025083A1
Автор: Botham Rachel C., Fan Timothy M., Gilbert Mark J., Handley Michael J., HERGENROTHER Paul J., Joshi Avadhut, RIGGINS Gregory J., Tarasow Theodore M.
Принадлежит:

The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds. 2. The composition of wherein the carrier comprises water and optionally a buffer claim 1 , a cyclodextrin claim 1 , or a combination thereof.3. The composition of wherein the cyclodextrin is 2-hydroxypropyl-β-cyclodextrin.4. The composition of wherein the concentration of the compound of Formula I is about 100 μM to about 1 mM.5. The composition of wherein the concentration of PAC-1 is about 2 μM to about 50 μM.6. The composition of wherein the concentration of the compound of Formula I is about 250 μM to about 750 μM and he concentration of PAC-1 is about 5 μM to about 30 μM.7. A method of inhibiting the growth or proliferation of cancer cells comprising contacting cancer cells with an effective amount of a composition of claim 1 , thereby inhibiting the growth or proliferation of the cancer cells.8. The method of wherein the cancer cells are glioblastoma cells or oligodendroglioma cells.9. The method of wherein the cancer cells are osteosarcoma cells.11. The method of wherein the contacting is in vitro.12. The method of wherein the contacting is in vivo.13. The method of wherein the cancer cell is contacted with the compound of Formula (I) and the PAC-1 concurrently.14. The method of wherein the cancer cell is contacted with the compound of Formula (I) prior to contacting the cancer cell with PAC-1.15. The method of wherein the cancer cell is contacted with PAC-1 prior to contacting the cancer cell with the compound of Formula (I).17. The method of wherein the compound of Formula (I) and the compound PAC-1 are administered concurrently.18. The method ...

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Номер записи: 62
28-01-2021 дата публикации

PHENYLALANINE DERIVATIVES FOR USE IN THE TREATMENT OF CANCERS

Номер: US20210023034A1
Автор: CASTELLANO FLAVIA, LE GALL ERWAN, MOLINIER FRENKEL VALÉRIE, PRESSET MARC
Принадлежит:

The present invention relates to the field of medicine, in particular of oncology. Especially, it provides new compounds useful in the treatment of various cancers. The present invention relates more particularly to methods for the treatment of cancer with IL4I1 expressing cells. 113-. (canceled)15. The method according to claim 14 , wherein the compound of formula (I) meets at least one of the following features:{'sub': 1', '4', '2', '4, 'R1 is a (C-C) alkyl group or a phenyl group, and R2 is an hydrogen atom or a (C-C) alkyl group,'}{'sub': 1', '8', '1', '8', '6', '18', '1', '4, 'R1 and R2 form together a ring with the nitrogen atom to which they are attached, wherein said ring is selected in the group consisting of piperazine, morpholine, thiomorpholine and piperidine groups, said ring being optionally substituted with at least one halogen atom or a (C-C)alkyl group, R3 is an hydrogen atom, a (C-C)alkyl group, or a (C-C)aryl(C-C)alkyl group,'}{'sub': 1', '4', '3, 'the phenyl group is unsubstituted or substituted with one to five substituents which are independently selected in the group consisting of chlorine, a (C-C)alkyl, cyano or CFgroup,'}R3 is an hydrogen atom, a methyl, ethyl, propyl or benzyl group, andR4 and R5 represent hydrogen atoms.16. The method according to claim 14 , wherein the compound is of formula (I) where R1 is an aryl group that is unsubstituted or substituted by at least one halogen atom claim 14 , hydroxy group claim 14 , alkyl group claim 14 , alkoxy group claim 14 , aryl group claim 14 , aryloxy group claim 14 , acid group claim 14 , cyano claim 14 , ester group or a mixture thereof claim 14 , said substituent(s) optionally being substituted by at least one halogen atom claim 14 , hydroxy group claim 14 , alkoxy group claim 14 , aryl group claim 14 , aryloxy group claim 14 , acid group claim 14 , cyano claim 14 , or ester group.17. The method according to claim 14 , wherein the compound is of formula (I) where R1 is a phenyl group claim ...

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Номер записи: 63
04-02-2016 дата публикации

Brain, Spinal and Nerve Injury Treatment

Номер: US20160030474A1
Автор: Nimmo Alan John, Vink Robert
Принадлежит:

A treatment for brain, spinal and nerve injury comprising use of a substance P receptor antagonist optionally in combination with a magnesium compound. There is also provided a formulation for use in this treatment comprising a substance P receptor antagonist and a magnesium compound. 1. A method of treating a mechanical traumatic brain , spinal cord or nerve tissue injury by substantially reducing a secondary injury caused by a vasogenic edema in the brain comprising administering to a patient in need of such treatment , a therapeutically effective amount of pharmaceutical preparation comprising:a therapeutically effective amount of a substance P receptor antagonist selected from the group consisting of:N-(3,5-Bis-trifluoromethyl-benzyl)-N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide,2′-Methyl-5-(4-methyl-piperazin-1-yl)-biphenyl-2-carboxylic acid-(3,5-bis-trifluoromethyl-benzyl)-methyl-amide,N-(3,5-Bis-trifluoromethyl-benzyl)-N-methyl-6-(4-methyl-piperazin-1-yl)-4-naphthalen-1-yl-nicotinamide,(4-{5-[(3,5-Bis-trifluoromethyl-benzyl)-methyl-carbamoyl]-4-o-tolyl-pyridin-2-yl}-piperazin-1-yl)-acetic acid ethyl ester,N-(3,5-Bis-trifluoromethyl-benzyl)-N-methyl-6-(4-propyl-piperazin-1-yl)-4-o-tolyl-nicotinamide,N-(3,5-Bis-trifluoromethyl-benzyl)-N-methyl-6-[methyl-(2-morpholin-4-yl-ethyl)-amino]-4-o-tolyl-nicotinamide,N-(3,5-Bis-trifluoromethyl-benzyl)-N-methyl-6-morpholin-4-yl-4-o-tolyl-nicotinamide,N-(3,5-Bis-trifluoromethyl-benzyl)-N-methyl-6-piperazin-1-yl-4-o-tolyl-nicotinamide,N-(3,5-Bis-trifluoromethyl-benzyl)-6-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-N-methyl-4-o-tolyl-nicotinamide,N-(3,5-Bis-trifluoromethyl-benzyl)-6-(4-cyanomethyl-piperazin-1-yl)-N-methyl-4-o-tolyl-nicotinamide,N-(3,5-Bis-trifluoromethyl-benzyl)-6-{4-[2-(2-hydroxy-ethoxy)-ethyl]-piperazin-1-yl}-N-methyl-4-o-tolyl-nicotinamide,N-(3,5-Bis-trifluoromethyl-benzyl)-N-methyl-6-(4-[1,2,4]oxadiazol-3-ylmethyl-piperazin-1-yl)-4-o-tolyl-nicotinamide,N— (3,5-Bis-trifluoromethyl-benzyl)-N-methyl ...

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Номер записи: 64
01-02-2018 дата публикации

Role of N-2-Hydroxy-Ethyl-Piperazine-N'-2-Ethane Sulfonic Acid (HEPES) in Pain Control and Reversal of Demyelinization Injury

Номер: US20180028530A1
Автор: Danhof Ivan E.
Принадлежит:

Compositions and therapeutic uses of HEPES and derivatives in the treatment of pain associated with cancers and side-effects including post-chemotherapy cognitive impairment are disclosed herein. HEPES is also used to treat neurodegenerative and neurological diseases, demyelinization injuries, and side-effects and withdrawal symptoms associated with benzodiazepines, anti-depressants, and other neurological agents. 1. A method of treating neurological impairment caused by one or more demyelination diseases , withdrawal symptoms , side-effects or both following treatment with anti-depressants , selective serotonin inhibitors (SSRI) , or other neurological agents that cause demyelination in a subject in a human subject comprising the steps of:identifying a subject in need for treatment against the neurological impairment caused by one or more demyelination diseases, withdrawal symptoms, side-effects or both following treatment with anti-depressants, selective serotonin inhibitors (SSRI), or other neurological agents that cause demyelination; andadministering a pharmaceutical composition comprising N-2-hydroxy-ethyl-piperazine-N′-2-ethane sulfonic acid (HEPES) and derivatives thereof dissolved in sterile water, buffer, saline or other pharmaceutically acceptable carriers once daily at a dosage of 10-100 mg/kg of body weight, wherein the pharmaceutical composition is administered orally, subcutaneously, parenterally, intravenously, peritoneally, or intramuscularly.2. The method of claim 1 , wherein the anti-depressants are selected from the group consisting of benzodiazepines claim 1 , SSRIs claim 1 , Serotonin-norepinephrine reuptake inhibitors (SNRIs) claim 1 , Noradrenergic and specific serotonergic antidepressants (NaSSAs) claim 1 , Norepinephrine (noradrenaline) reuptake inhibitors (NRIs) claim 1 , Norepinephrine-dopamine reuptake inhibitors (NDRIs) claim 1 , Selective serotonin reuptake enhancers (SSREs) claim 1 , Melatonergic agonists claim 1 , Tricyclic ...

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Номер записи: 65
24-04-2014 дата публикации

MCL-1 AS A THERAPEUTIC TARGET IN SCFFBW7 DEFICIENT NEOPLASM

Номер: US20140113913A1
Автор: Wei Wenyi
Принадлежит: BETH ISRAEL DEACONESS MEDICAL CENTER, INC.

Some embodiments are based on the discovery that proliferative diseases (e.g., neoplastic diseases, for example, tumors or cancers) having an FBW7 mutation or other FBW7 deficiency are sensitive to Mcl1 inhibiting agents, but resistant to pro-apoptotic drugs that do not inhibit Mcl1. Some embodiments provide methods of treating a proliferative disease based on an assessment of FBW7 expression level or mutation status. Some embodiments provide methods of classifying a hyperproliferative cell or cell population, for example, a malignant cell or cell population based on an assessment of FBW7 expression level or mutation status. Some embodiments provide methods of selecting a treatment regimen for treating a proliferative disease, for example, a malignant disorder, based on an assessment of FBW7 expression level or mutation status. 1. A method for treating a proliferative disease comprising(a) obtaining a cell from a subject diagnosed with a proliferative disease if the cell is FBW7 deficient, the subject is indicated to be a candidate for treatment with a drug inhibiting Mcl-1; and/or', 'if the cell is not FBW7 deficient, the subject is not indicated to be a candidate for treatment with a drug inhibiting Mcl-1 and/or the subject is indicated to be a candidate for treatment with a pro-apoptotic drug., '(b) determining whether the cell is FBW7 deficient; wherein'}2. The method of claim 1 , wherein the proliferative disease is a neoplastic disease.3. The method of claim 1 , wherein the proliferative disease is a malignant disease.4. The method of claim 1 , wherein the proliferative disease is a cancer.5. The method of claim 1 , wherein the proliferative disease is a leukemia.6. The method of claim 1 , wherein the proliferative disease is T-ALL.7. The method of claim 1 , wherein the determining whether the cell is FBW7 is deficient comprises assessing the mutation status of the FBW7 gene in the cell; whereinif the cell does not comprise a mutation of the FBW7 gene, then ...

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Номер записи: 66
29-01-2015 дата публикации

9-azanoradamantane n-oxyl compound and method for producing same, and organic oxidation catalyst and method for oxidizing alcohols using 9-azanoradamantane n-oxyl compound

Номер: US20150031887A1
Автор: Masatoshi Shibuya, Ryusuke Doi, Yoshiharu Iwabuchi
Принадлежит: Tohoku University NUC

An organocatalyst for oxidizing alcohols in which a primary alcohol is selectively oxidized in a polyol substrate having a plurality of alcohols under environmentally-friendly conditions. The organic oxidation catalyst has an oxygen atom bonded to a nitrogen atom of an azanoradamantane skeleton and at least one alkyl group at positions 1 and 5. The oxidation catalyst has higher activity than TEMPO, which is an existing oxidation catalyst, in the selective oxidation reaction of primary alcohols, and better selectivity than AZADO and 1-Me-AZADO. This DMN-AZADO can be applied to the selective oxidation reaction of primary alcohols that contributes to shortening the synthesizing process for pharmaceuticals, pharmaceutical raw materials, agricultural chemicals, cosmetics, organic materials, and other such high value-added organic compounds.

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Номер записи: 67
17-02-2022 дата публикации

PRODUCT AND METHOD FOR TREATING DIARRHEA

Номер: US20220047583A1
Автор: Hogan, II Reed B.
Принадлежит:

A method of treating diarrhea in a patient includes administering an H1 receptor antagonist and an H2 receptor antagonist to the patient. 1. A method of treating diarrhea in a patient , comprising administering an H1 receptor antagonist and an H2 receptor antagonist to the patient , wherein the patient does not have mastocytic enterocolitis.2. (canceled)3. The method of claim 1 , wherein the H1 receptor antagonist comprises cetirizine claim 1 , levocetirizine claim 1 , or mixtures thereof.4. The method of claim 1 , wherein the H2 receptor antagonist comprises famotidine claim 1 , ranitidine claim 1 , or mixtures thereof.5. The method of claim 1 , wherein the H1 receptor antagonist and the H2 receptor antagonist are administered simultaneously.6. The method of claim 1 , wherein the H1 receptor antagonist and the H2 receptor antagonist are administered once per day for at least 2 days.7. The method of claim 1 , wherein the H1 receptor antagonist and the H2 receptor antagonist are administered once per day for at least 7 days.817-. (canceled)18. The method of claim 1 , wherein the H1 receptor antagonist comprises cetirizine and the cetirizine is administered in an amount of 5 to 20 mg.19. The method of claim 1 , wherein the H2 receptor antagonist comprises famotidine and the famotidine is administered in an amount of 10 to 40 mg.20. The method of claim 1 , wherein the H1 receptor antagonist comprises cetirizine claim 1 ,the H2 receptor antagonist comprises famotidine, andthe famotidine and the cetirizine are administered together as a unit dosage form.2140-. (canceled)41. A pharmaceutical composition for treating diarrhea claim 1 , comprising:an H1 receptor antagonist, andan H2 receptor antagonist,wherein the H2 receptor antagonist is not ranitidine, andthe pharmaceutical composition is an oral dosage form.42. (canceled)43. The pharmaceutical composition of claim 41 , wherein the H1 receptor antagonist comprises cetirizine claim 41 , levocetirizine claim 41 , or ...

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Номер записи: 68
30-01-2020 дата публикации

Dosing Regimens for Fast Onset of Antidepressant Effect

Номер: US20200030319A1
Автор: Bang-Andersen Benny, Morillo Connie Sanchez, Søby Karina Krøjer
Принадлежит:

A dose regimes comprising the simultaneous administration of two pharmaceutical compositions, wherein the first pharmaceutical composition is a composition comprising vortioxetine or a pharmaceutically acceptable salt thereof for once daily oral administration, and the second pharmaceutical composition is a composition comprising vortioxetine or a pharmaceutically acceptable salt thereof which together with said first composition quickly achieves a steady-state plasma level of vortioxetine in said patient which steady-state plasma level is the same as the steady-state vortioxetine plasma level achieved by the administration to said patient of said first composition alone. 1. A method for the treatment of depression , said method comprising:simultaneously administering two pharmaceutical compositions to a patient in need thereof,wherein the first pharmaceutical composition is a composition comprising vortioxetine or a pharmaceutically acceptable salt thereof for once daily oral administration, and the second pharmaceutical composition is a composition comprising vortioxetine or a pharmaceutically acceptable salt thereof which, together with said first composition, achieves a steady-state plasma level of vortioxetine in said patient within 36 hours from said simultaneous administration, which steady-state plasma level is essentially the same as the steady-state vortioxetine plasma level achieved by the administration to said patient of said first composition alone; andwherein said second pharmaceutical composition is administered nasally.2. The method of claim 1 , wherein said first pharmaceutical composition comprises 5 mg-20 mg vortioxetine or a pharmaceutically acceptable salt thereof claim 1 , and the second pharmaceutical composition is a composition comprising vortioxetine or a pharmaceutically acceptable salt thereof which claim 1 , together with said first composition claim 1 , achieves a steady-state plasma level between 68 ng h/ml and 1625 ng h/ml ...

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Номер записи: 69
31-01-2019 дата публикации

INTEGRATED PROCESS FOR THE PRODUCTION OF FORMALDEHYDE-STABILISED UREA

Номер: US20190031604A1
Автор: ERLANDSSON Ola, MAGNUSSON Andreas Erik Johan, MCFARLANE Kate, PACH John David, SHELDON Daniel Thomas, WARD Darren
Принадлежит:

A process for the production of formaldehyde-stabilised urea is described comprising the steps of: (a) generating a synthesis gas comprising hydrogen, nitrogen, carbon monoxide, carbon dioxide and steam in a synthesis gas generation unit, (b) subjecting the synthesis gas to one or more stages of water-gas shift in one or more water-gas shift reactors to form a shifted gas; (c) recovering carbon dioxide from the shifted gas in a carbon dioxide removal unit to form a carbon dioxide-depleted synthesis gas; (d) synthesising methanol from the carbon dioxide-depleted synthesis gas in a methanol synthesis unit and recovering the methanol and a methanol synthesis off-gas comprising nitrogen, hydrogen and residual carbon monoxide; (e) subjecting at least a portion of the recovered methanol to oxidation with air in a formaldehyde production unit; (f) subjecting the methanol synthesis off-gas to methanation in a methanation reactor containing a methanation catalyst to form an ammonia synthesis gas; (g) synthesising ammonia from the ammonia synthesis gas in an ammonia production unit and recovering the ammonia; (h) reacting a portion of the ammonia and at least a portion of the recovered carbon dioxide stream in a urea production unit to form a urea stream; and (i) stabilising the urea by mixing the urea stream and a stabiliser prepared using formaldehyde recovered from the formaldehyde production unit, wherein a portion of the synthesis gas generated by the synthesis gas generation unit by-passes either the one or more water-gas shift reactors; the carbon dioxide removal unit; or the one or more water-gas shift reactors and the carbon dioxide removal unit. 2. The process according to wherein the synthesis gas is generated by steam reforming a hydrocarbon or gasifying a carbonaceous feedstock.3. The process according to claim 1 , wherein the synthesis gas is generated by adiabatic pre-reforming claim 1 , primary reforming in a fired or gas-heated steam reformer and secondary or ...

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Номер записи: 70
04-02-2021 дата публикации

METHODS OF TREATING NEOPLASTIC ASTROCYTOMA

Номер: US20210032366A1
Автор: Burgess Antony Wilks, Cavenee Webster K., Collins Vincent Peter, Huang Huei-Jen Su, Johns Terrance Grant, Jungbluth Achim, Mark George, Murray Anne, Nice Edouard Collins, Old Lloyd J., Panousis Con, Renner Christoph, Ritter Gerd, SCOTT Andrew M., Stockert Elisabeth
Принадлежит:

The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to amplified epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof, is enhanced or evident upon aberrant post-translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof. 1. A method of treating a neoplastic astrocytoma in a human subject , the method comprising administering to the subject a therapeutically effective amount of an isolated anti-Epidermal Growth Factor Receptor (EGFR) antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 164 , and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 166.2. The method according to claim 1 , wherein the heavy chain comprises the constant region set forth in SEQ ID NO: 43.3. The method according to claim 1 , wherein the light chain comprises the constant region set forth in SEQ ID NO: 48.4. The method according to claim 3 , wherein the antibody is an IgG isotype.5. The method according to claim 4 , wherein the IgG isotype is an IgG1 isotype.6. The method according to claim 1 , wherein the antibody is conjugated to a cytotoxic agent.7. The method according to claim 1 , wherein the antibody is administered in combination with temozolomide.8. A method of treating a neoplastic astrocytoma in a human subject claim 1 , the method comprising administering to the subject a therapeutically effective amount of an isolated anti-Epidermal Growth Factor Receptor (EGFR) antibody claim 1 , wherein the antibody is capable of binding EGFR on tumors ...

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Номер записи: 71
09-02-2017 дата публикации

AZA Spiro Alkane Derivatives as Inhibitors of Metalloproteases

Номер: US20170035751A1
Автор: Metcalf Brian W., Xu Meizhong, Yao Wenqing, Zhang Fenglei, Zhuo Jincong
Принадлежит:

The present invention provides a compound of Formula I or Formula II: 195-. (canceled)97. The method of claim 96 , wherein Y is CH.98. The method of claim 96 , wherein V′ is phenyl.99. The method of claim 96 , wherein Ris H.100. The method of claim 96 , wherein Ris C(O)(CR′R′)-T.101. The method of claim 96 , wherein Ris C(O)O(CR′R′)-T.102. The method of claim 96 , wherein the compound is selected from:N-hydroxy-6-{[4-(3-methylphenyl)piperazin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;Methyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3, 6-dihydropyridin-1(2H)-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate;Benzyl 7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate;6-{[4-[3-(aminocarbonyl)phenyl]-3,6-dihydropyridin-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide;6-{[4-(3-fluoro-2-methylphenyl)piperazin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide;N-hydroxy-6-{[4-(2-methyl-3-nitrophenyl)piperazin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;N-hydroxy-6-{[3-methyl-4-(3-methylphenyl)piperazin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;N-hydroxy-6-{[4-(3-methoxyphenyl)piperidin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;6-{[4-(4-cyano-2-methylphenyl)-3,6-dihydropyridin-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide;6-{[4-(4-cyanophenyl)piperazin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide;N-hydroxy-6-[(4-phenylpiperidin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;N-Hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;Methyl 3-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2.5]oct-6-yl}carbonyl)piperidin-4-yl]benzoate;N-Hydroxy-6-{[4-(3-isopropylphenyl)-3, 6-dihydropyridin-1(2H)-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;N-hydroxy-6-{[4-(3-isopropylphenyl)piperidin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;N-hydroxy-6-{[4-(4-propylphenyl)-3,6-dihydropyridin-1(2H)-yl] ...

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Номер записи: 72
07-02-2019 дата публикации

PRODUCT AND METHOD FOR TREATING DIARRHEA

Номер: US20190038619A1
Автор: Hogan Reed B.
Принадлежит:

A method of treating diarrhea in a patient includes administering an H1 receptor antagonist and an H2 receptor antagonist to the patient. 1. A method of treating diarrhea in a patient ,comprising administering an H1 receptor antagonist and an H2 receptor antagonist to the patient, wherein the patient has chronic idiopathic diarrhea.2. The method of claim 1 , wherein the H1 receptor antagonist comprises a second-generation H1 receptor antagonist.3. The method of claim 1 , wherein the H1 receptor antagonist comprises cetirizine claim 1 , levocetirizine claim 1 , or mixtures thereof.4. The method of claim 1 , wherein the H2 receptor antagonist comprises famotidine claim 1 , ranitidine claim 1 , or mixtures thereof.5. The method of claim 1 , wherein the H1 receptor antagonist and the H2 receptor antagonist are administered simultaneously.6. The method of claim 1 , wherein the H1 receptor antagonist and the H2 receptor antagonist are administered once per day for at least 2 days.7. The method of claim 1 , wherein the H1 receptor antagonist and the H2 receptor antagonist are administered once per day for at least 7 days.810-. (canceled)11. The method of claim 1 , wherein the H1 receptor antagonist comprises cetirizine and the H2 receptor antagonist comprises famotidine.1217-. (canceled)18. The method of claim 11 , wherein cetirizine is administered in an amount of 5 to 20 mg.19. The method of claim 11 , wherein the famotidine is administered in an amount of 10 to 40 mg.20. The method of claim 11 , wherein the famotidine and the cetirizine are administered together as a unit dosage form.2180-. (canceled)81. The method of claim 11 , wherein the famotidine and the cetirizine are administered together as an oral dosage form.82. The method of claim 81 , wherein the oral dosage form comprises at least one tablet or capsule.83. The method of claim 81 , wherein the oral dosage form further comprises sodium claim 81 , and glucose or a glucose-containing saccharide.84. The method ...

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Номер записи: 73
07-02-2019 дата публикации

DELTA OPIOID AGONIST MU OPIOID ANTAGONIST COMPOSITIONS AND METHODS FOR TREATING PARKINSONS DISEASE

Номер: US20190038620A1
Автор: REIDENBERG BRUCE, VERSI EBRAHIM
Принадлежит:

The present invention provides for compositions and methods for the treatment of Parkinson's disease comprising a compound of formula (i): 2. The method of claim 1 , wherein the therapeutically effective amount of formula (i) is sufficient to delay or eliminate the need for invasive deep brain stimulation in a subject suffering from Parkinson's disease.3. The method of wherein the compound of formula (i) is administered in a dose ranging from about 1 to about 100 mg/kg claim 1 , preferably 5-20 mg/kg in humans45.-. (canceled)7. The method of claim 6 , wherein the reduced amount of L-DOPA ranges from an amount from 1 to 10 mg/kg/day of L-DOPA.8. The method of wherein the compound of formula (i) is administered in a dose ranging from about 1 to about 100 mg/kg claim 6 , preferably 5-20 mg/kg per day.9. The method of wherein the compound of formula (i) is administered in a dose ranging from about 1 to about 100 mg/kg claim 6 , preferably 5-20 mg/kg per day which results in prolongation of the duration of effect of a single sub-therapeutic dose of L-DOPA.11. The method of claim 10 , further comprising a dose of L-DOPA in an amount from about 1 to 10 mg/kg/day.12. The method of claim 10 , wherein the compound of formula (i) is administered in a dose ranging from about 1 to about 100 mg/kg/day.14. (canceled)16. The method of wherein the compound formula (i) is administered in a dose of the compound would be 1-100 mg/kg claim 15 , preferably 5-20 mg/kg.17. The method of claim 15 , wherein the L-DOPA is the lowest individualized dose that provides relief to the subject claim 15 , in an amount from 50 mg to 1000 mg of L-DOPA. This application claims priority to U.S. Provisional Patent Application No. 62/315,717, filed on Mar. 31, 2016, the contents of which are hereby incorporated by reference herein for all purposes.The present invention relates to compositions and methods of treatment for Parkinson's disease, by administration to a subject suffering or susceptible to same, ...

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Номер записи: 74
18-02-2016 дата публикации

TREATMENT OF JOINT CONDITIONS

Номер: US20160045493A1
Автор: Bar-Or David
Принадлежит:

The invention provides a method of treating a joint condition. The method comprises administering a multi-dose regimen of a pharmaceutical composition comprising a diketopiperazine with amino acid side chains of aspartic acid and alanine (DA-DKP). The invention also provides a method of treating osteoarthritis with multiple doses of a low-molecular weight fraction of human serum albumin. 1. A method of treating a joint condition comprising administering to an animal in need thereof an effective amount of a pharmaceutical composition comprising DA-DKP in a multi-dose regimen.2. The method of claim 1 , wherein the joint condition is a joint disease.3. The method of claim 2 , wherein the joint disease is a degenerative joint disease.4. The method of claim 3 , wherein the degenerative joint disease is osteoarthritis.5. The method of claim 1 , wherein the joint condition is a joint injury.6. The method of claim 5 , wherein the joint injury is at least one of a traumatic injury and a post-operative injury.7. The method of claim 5 , wherein the joint injury is a repetitive strain injury.8. The method of claim 1 , wherein the joint condition is inflammation.9. The method of claim 1 , wherein the composition is administered by an administration route selected from the group consisting of local administration claim 1 , topical administration claim 1 , and injection.10. The method of claim 9 , wherein administration by injection is by intra-articular injection.11. The method of claim 10 , wherein the composition administered by intra-articular injection is a composition having a concentration of DA-DKP from about 50 μM to about 350 μM.12. The method of claim 1 , wherein the composition further comprises N-acetyl-tryptophan (NAT) claim 1 , caprylic acid claim 1 , caprylate or combinations thereof.13. The method of claim 10 , wherein the composition is a composition having a concentration of NAT claim 10 , caprylic acid claim 10 , caprylate or combinations thereof from about 4 ...

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Номер записи: 75
16-02-2017 дата публикации

PROCASPASE COMBINATION THERAPY FOR GLIOBLASTOMA

Номер: US20170042886A1
Автор: Botham Rachel C., Fan Timothy M., Gilbert Mark J., Handley Michael J., HERGENROTHER Paul J., Joshi Avadhut, RIGGINS Gregory J., Tarasow Theodore M.
Принадлежит:

The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods of use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds. 2. The method of wherein the cancer is cancer of the brain claim 1 , cancer of bone claim 1 , breast cancer claim 1 , colon cancer claim 1 , liver cancer claim 1 , lung cancer claim 1 , lymphoma claim 1 , melanoma claim 1 , or renal cancer.3. The method of wherein the cancer is cancer of the brain.4. The method of wherein the cancer is cancer of bone.5. The method of wherein the concentration of the compound of Formula I is about 100 μM to about 1 mM.6. The method of wherein the concentration of PAC-1 is about 2 μM to about 50 μM.7. The method of wherein the cancer is cancer of the brain claim 1 , the concentration of the compound of Formula I is about 100 μM to about 1 mM claim 1 , and the concentration of PAC-1 is about 2 μM to about 50 μM.8. The method of wherein the concentration of the compound of Formula I is about 250 μM to about 750 μM and the concentration of PAC-1 is about 5 μM to about 30 μM.9. The method of wherein the cancer is cancer of bone claim 1 , the concentration of the compound of Formula I is about 100 μM to about 1 mM claim 1 , and the concentration of PAC-1 is about 2 μM to about 50 μM.10. The method of wherein the concentration of the compound of Formula I is about 250 μM to about 750 μM and the concentration of PAC-1 is about 5 μM to about 30 μM.11. The method of wherein the cancer is breast cancer claim 1 , colon cancer claim 1 , liver cancer claim 1 , lung cancer claim 1 , lymphoma claim 1 , melanoma claim 1 , or renal cancer claim 1 , and the concentration of the compound of Formula I is about 100 μM to about 1 mM claim 1 , ...

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Номер записи: 76
15-02-2018 дата публикации

METHOD OF TREATING A BRAIN TUMOR

Номер: US20180042921A1
Автор: Huang Lan
Принадлежит:

Disclosed herein are methods of treating a brain tumor by administering Plinabulin. Some embodiments relate to treatment of glioblastoma multiforme by administering Plinabulin. 1. A method of treating a brain tumor comprising administering an effective amount of Plinabulin to a subject in need thereof.2. The method of any of claim 1 , wherein the brain tumor is metastatic brain tumor claim 1 , anaplastic astrocytoma claim 1 , glioblastoma multiforme claim 1 , oligodendroglioma claim 1 , ependymomas claim 1 , or a combination thereof.3. The method of claim 2 , wherein the brain tumor is a glioblastoma multiforme.4. The method of claim 2 , wherein the brain tumor is a metastatic brain tumor.5. The method of claim 1 , further comprising administering an additional therapeutic agent.6. The method of claim 5 , wherein the additional therapeutic agent is temozolomide.7. The method of claim 1 , further comprising subjecting the subject to radiation therapy.8. The method of claim 1 , wherein the brain tumor is characterized by expression of a mutant form of KRAS.9. A method of inhibiting proliferation of brain tumor cell claim 1 , comprising contacting the brain tumor cell with Plinabulin.10. The method of claim 9 , wherein contacting comprises administering an effective amount of Plinabulin to a subject having the brain tumor cell.11. A method of inducing apoptosis in brain tumor cell claim 9 , comprising contacting the brain tumor cell with Plinabulin.12. The method of claim 11 , wherein contacting comprises administering an effective amount of Plinabulin to a subject having the brain tumor cell.13. (canceled) This application claims the benefit of U.S. Provisional Application No. 62/129,623, filed Mar. 6, 2015, and U.S. Provisional Application No. 62/249,807, filed Nov. 2, 2015, the disclosure of which are incorporated herein by reference in their entireties.The present invention relates to the field of chemistry and medicine. More particularly, the present invention ...

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Номер записи: 77
18-02-2016 дата публикации

SPECIFIC BINDING PROTEINS AND USES THEREOF

Номер: US20160046726A1
Автор: Burgess Antony Wilks, Cavenee Webster K., Collins Vincent Peter, Huang Huei-Jen Su, Johns Terrance Grant, Jungbluth Achim, Mark George, Murray Anne, Nice Edouard Collins, Old Lloyd J., Panousis Con, Renner Christoph, Ritter Gerd, SCOTT Andrew M., Stockert Elisabeth
Принадлежит:

The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to amplified epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof, is enhanced or evident upon aberrant post-translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof. 1. A method of treating a human subject having a tumor , the method comprising administering to the subject a therapeutically effective amount of an isolated anti-Epidermal Growth Factor Receptor (EGFR) antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 164 , and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 166.2. The method according to claim 1 , wherein the heavy chain comprises the constant region set forth in SEQ ID NO: 43.3. The method according to claim 1 , wherein the light chain comprises the constant region set forth in SEQ ID NO: 48.4. The method according to claim 3 , wherein the antibody is an IgG isotype.5. The method according to claim 4 , wherein the IgG isotype is an IgG1 isotype.6. The method according to claim 1 , wherein the tumor is a solid tumor.7. The method according to claim 6 , wherein the solid tumor is selected from the group consisting of a breast tumor claim 6 , a lung tumor claim 6 , a prostate tumor claim 6 , a bladder tumor claim 6 , a head tumor claim 6 , and a neck tumor.8. The method according to claim 6 , wherein the solid tumor is a glioma.9. The method according to claim 6 , wherein the solid tumor is an epithelial tumor.10. The method according to claim 1 , wherein the ...

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Номер записи: 78
19-02-2015 дата публикации

METHOD OF USING DIKETOPIPERAZINES AND COMPOSITION CONTAINING THEM

Номер: US20150051223A1
Автор: Bar-Or David, Curtis C. Gerald, Rao Nagaraja K.R., Thomas Greg
Принадлежит:

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: 2. The method of wherein Ris —CHCOOH.3. The method of wherein Ris the side chain of alanine.4. The method of wherein Ris the side chain of alanine.528.-. (canceled)29. The method of claim 1 , wherein the compound is administered as a pharmaceutical formulation.30. The method of claim 29 , wherein the pharmaceutical formation is a topical formulation.31. The method of claim 30 , wherein the topical formulation is an ointment claim 30 , a paste claim 30 , a cream claim 30 , a gel claim 30 , a lotion claim 30 , a powder or a spray.32. A method of treating psoriasis comprising topically applying to an animal in need thereof claim 30 , a pharmaceutical composition wherein the pharmaceutical composition comprises 3-methyl-2 claim 30 ,5-diketopiperazine-6-acetic acid and is formulated for topical administration. This application is a continuation of U.S. application Ser. No. 13/252,377, filed Oct. 4, 2011, which is a continuation of U.S. application Ser. No. 10/397,964, filed Mar. 25, 2003, now U.S. Pat. No. 8,455,517, which is a continuation of issued U.S. Pat. No. 6,555,543, filed Aug. 2, 2001 and issued Apr. 29, 2003, which claims benefit of provisional application 60/222,849, filed Aug. 4, 2000. The entire disclosure of the prior applications, are hereby incorporated by reference.This invention relates to methods of inhibiting the effects of platelet activating is factor using certain diketopiperazines. The invention also relates to methods of inhibiting the production and/or release of interleukin ...

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Номер записи: 79
25-02-2016 дата публикации

Novel Dispersible Tablet Composition

Номер: US20160051476A1
Автор: Bagde Pradnya, Barve Varsha, Gandhi Anilkumar Surendrakumar, Pilgaonkar Pratibha Sudhir, Rustomjee Maharukh Tehmasp
Принадлежит: RUBICON RESEARCH PVT. LTD.

Disclosed herein is a dispersible tablet composition including a pharmacologically active ingredient and at least one excipient that reduces the sedimentation rate of the active ingredient and a process for preparing the same. 1. A dispersible tablet composition comprising(a) at least one pharmacologically active ingredient;(b) at least one hydrophilic polymer that reduces the sedimentation rate of the pharmacologically active ingredient; and(c) at least one disintegrant.2. The dispersible tablet composition of claim 1 , wherein the pharmacologically active ingredient is selected from canti-cancer agents claim 1 , antitussives claim 1 , antihistamines claim 1 , decongestants claim 1 , alkaloids claim 1 , mineral supplements claim 1 , laxatives claim 1 , vitamins claim 1 , antacids claim 1 , anti-cholesterolemic claim 1 , anti-lipid agents claim 1 , antiarrhythmics claim 1 , antipyretics claim 1 , analgesics claim 1 , appetite suppressants claim 1 , expectorants claim 1 , anti-anxiety agents claim 1 , anti-ulcer agents claim 1 , anti-inflammatory substances claim 1 , coronary dilators claim 1 , cerebral dilators claim 1 , peripheral vasodilators claim 1 , anti-infectives claim 1 , psychotropic claim 1 , antimanics claim 1 , stimulants claim 1 , gastrointestinal agents claim 1 , sedatives claim 1 , antidiarrheal preparations claim 1 , anti-anginal drugs claim 1 , vasodilators claim 1 , anti-hypertensive drugs claim 1 , vasoconstrictors claim 1 , migraine treatments claim 1 , antibiotics claim 1 , tranquilizers claim 1 , anti-psychotics claim 1 , antitumor drugs claim 1 , anticoagulants claim 1 , antithrombotic drugs claim 1 , hypnotics claim 1 , anti-emetics claim 1 , anti-nauseants claim 1 , anti-convulsants claim 1 , neuromuscular drugs claim 1 , hyper- and hypoglycemic agents claim 1 , thyroid and antithyroid preparation claim 1 , diuretics claim 1 , antispasmodics claim 1 , uterine relaxants claim 1 , mineral and nutritional additives claim 1 , antiobesity drugs ...

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Номер записи: 80
25-02-2016 дата публикации

METHODS OF ADMINISTRATION OF SINGLE DOSES OF VANOXERINE TO TERMINATE ACUTE EPISODES OF CARDIAC ARRHYTHMIA

Номер: US20160051542A1
Автор: Brown Arthur M.
Принадлежит:

Compositions and methods of treating patients suffering from symptoms of recent onset atrial fibrillation or atrial flutter comprising administration of a single dose of about 200 to about 400 mg of vanoxerine to return said patient to normal sinus rhythm in less than about 24 hours. 1. A method for restoring normal sinus rhythm to a patient suffering from recent onset symptomatic atrial fibrillation or atrial flutter in less than about 24 hours by administering to said patient at least 200 mg of vanoxerine.2. The method of comprising at least 300 mg of vanoxerine.3. The method of comprising at least 400 mg of vanoxerine.4. The method of wherein the patient is returned to normal sinus rhythm in less than about 12 hours.5. The method of wherein the patient is returned to normal sinus rhythm in less than about 8 hours.6. The method of wherein the patient is returned to normal sinus rhythm in less than about 4 hours.7. A method of treating a patient suffering from symptoms of atrial fibrillation or atrial flutter for less than about 72 hours comprising administration of about 200 to about 400 mg of vanoxerine.8. The method of wherein said patient is suffering from atrial fibrillation or atrial flutter symptoms for less than about 48 hours.9. The method of wherein said patient is suffering from atrial fibrillation or atrial flutter symptoms for less than about 24 hours.10. The method of wherein said patient is returned to normal sinus rhythm in less than about 24 hours.11. The method of wherein said patient is returned to normal sinus rhythm in less than about 8 hours.12. A method of treating a patient having recent onset of AF or AFL comprising administration of a single dose of a pharmaceutical composition comprising about 200 to about 400 mg of vanoxerine claim 7 , and wherein said patient is converted to normal sinus rhythm at a rate of at least 33% better than conversion as compared to placebo at a time period of 0-4 hours.13. The method of wherein the time period ...

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Номер записи: 81
25-02-2016 дата публикации

METHODS OF TREATMENT OF CARDIAC ARRHYTHMIAS USING VANOXERINE AND MODIFICATION OF DIET

Номер: US20160051543A1
Автор: Brown Arthur M.
Принадлежит:

Disclosed embodiments are related to methods of treatment of cardiac arrhythmias comprising administration of vanoxerine (GBR 12909) in connection with food of a predetermined fat content to modulate the plasma level concentrations of vanoxerine in a patient. 1. A method for administering vanoxerine for treatment of cardiac arrhythmia comprising:a. administering a first dose of vanoxerine to a patient;b. determining the bioavailability of the patient by measuring the physiological concentration of vanoxerine;c. calculating an effective dose of vanoxerine to be administered with a meal of a pre-determined fat content to be taken concurrently to modify the physiological concentration; andd. administering the effective dose of vanoxerine with the pre-determined meal.2. The method of wherein the meal has a fat content of at least 70 g and is taken directly before or concurrently with the vanoxerine dose.3. The method of wherein the meal has a fat content of at least 50 g and is taken directly before or concurrently with the vanoxerine dose.4. The method of wherein the meal has a fat content of at least 20 g and is taken directly before or concurrently with the vanoxerine dose.5. The method of wherein the meal has a fat content of less than 10 g and is taken directly before or concurrently with the vanoxerine dose.6. The method of wherein the meal is omitted and fasting is instituted with the effective dose of vanoxerine.7. A method for achieving a pre-determined plasma level comprising:a. administering a first dose of vanoxerine concurrently with a high-fat meal;b. measuring the physiological concentration of vanoxerine;c. comparing the physiological concentration to the pre-determined physiological concentration;d. modifying a further dose of vanoxerine to be given concurrently with a high-fat meal; ande. administering the second dosage of vanoxerine in conjunction with the high-fat meal.8. The method of wherein the pre-determined physiological concentration is taken ...

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Номер записи: 82
13-02-2020 дата публикации

Dry Powder Inhaler

Номер: US20200046917A1
Автор: Adamo Benoit, Guarneri Joseph, Kinsey P. Spencer, Laurenzi Brendan, Smutney Chad C.
Принадлежит:

A dry powder inhaler including replaceable cartridges containing a dry powder for local or systemic delivery through the pulmonary tract and lungs is disclosed. The inhalers are used with inhalable dry powders, including medicament formulations comprising active agents for local or systemic delivery and for the treatment of diseases such as, pulmonary hypertension, cardiovascular disease, anaphylaxis, diabetes, obesity, cancer, and other diseases, or symptoms associated with these and other diseases, such as nausea, vomiting, pain and inflammation. 1. A dry powder inhaler comprising:a housing, anda body comprising a mouthpiece integrally configured with the body,wherein the body comprises a mounting area for a cartridge, and the body and the housing are movable relative to one another linearly and are operably configured to engage one another by insertion to effectuate the cartridge to be reconfigured to attain an airflow pathway for discharging a powder dose upon an inhalation.2. The dry powder inhaler of claim 1 , wherein the mouthpiece has an air inlet for communicating with an interior compartment of the inhaler body.3. The dry powder inhaler of claim 1 , wherein the housing reconfigures the cartridge installed in the inhaler by translation of the housing over the inhaler body from an open configuration to a closed configuration.4. The dry powder inhaler of claim 1 , wherein the movement of the housing relative to the body is facilitated by guide rails structured along a longitudinal axis and extending from right side and/or left side of the inhaler body.5. The dry powder inhaler of claim 1 , wherein the dry powder inhaler is configured to attain an open or loading position claim 1 , and a closed or dosing position.6. The dry powder inhaler of claim 1 , wherein the housing further comprises a protruding rigid element which pushes the cartridge to a dosing position from a containment configuration.7. The dry powder inhaler of claim 1 , wherein the inhaler is ...

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Номер записи: 83
23-02-2017 дата публикации

PRODUCT AND METHOD FOR TREATING DIARRHEA

Номер: US20170049770A1
Автор: Hogan, II Reed B.
Принадлежит:

A method of treating diarrhea in a patient includes administering an H1 receptor antagonist and an H2 receptor antagonist to the patient. 1. A method of treating diarrhea in a patient , comprisingadministering an H1 receptor antagonist and an H2 receptor antagonist to the patient, wherein the patient does not have mastocytic enterocolitis.2. The method of claim 1 , wherein the H1 receptor antagonist comprises a second-generation H1 receptor antagonist.3. The method of claim 1 , wherein the H1 receptor antagonist comprises cetirizine claim 1 , levocetirizine claim 1 , or mixtures thereof.4. The method of claim 1 , wherein the H2 receptor antagonist comprises famotidine claim 1 , ranitidine claim 1 , or mixtures thereof.5. The method of claim 1 , wherein the H1 receptor antagonist and the H2 receptor antagonist are administered simultaneously.6. The method of claim 1 , wherein the H1 receptor antagonist and the H2 receptor antagonist are administered once per day for at least 2 days.7. (canceled)8. The method of claim 1 , wherein the patient has chronic diarrhea.9. The method of claim 1 , wherein the patient has IBS-D.10. The method of claim 1 , wherein the patient has acute diarrhea.11. A method of treating diarrhea in a patient claim 1 , comprising administering an H1 receptor antagonist and an H2 receptor antagonist to the patient claim 1 , wherein the H1 receptor antagonist comprises cetirizine and the H2 receptor antagonist comprises famotidine.1215-. (canceled)16. The method of claim 11 , wherein the patient has IBS-D.1718-. (canceled)19. The method of claim 11 , wherein the famotidine is administered in an amount of 10 to 40 mg.2040-. (canceled)41. A pharmaceutical composition for treating diarrhea claim 11 , comprising:an H1 receptor antagonist, andan H2 receptor antagonist,wherein the H2 receptor antagonist is not ranitidine, andthe pharmaceutical composition is an oral dosage form.42. (canceled)43. The pharmaceutical composition of claim 41 , wherein the H1 ...

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Номер записи: 84
22-02-2018 дата публикации

TEMOZOLOMIDE POWDER FORMULATION

Номер: US20180050032A1
Автор: Bryant Jeff, Payton Gary
Принадлежит:

The present invention relates to a solid pharmaceutical composition of temozolomide that has good and consistent flowability as a powder and taste masking and is readily dispersible in an aqueous solution suitable for oral administration, e.g., as a dry sprinkle. This permits patients and healthcare workers to accurately measure doses and safely dispense the drug. 2. The composition of claim 1 , wherein the emulsifiers are selected from sodium lauryl sulfate claim 1 , poloxamer claim 1 , saturated polyglycolized glyceride claim 1 , labrasol claim 1 , polysorbates claim 1 , sorbitan esters claim 1 , cremophor PEG-60 hydrogenated castor oil claim 1 , PEG-40 hydrogenated castor oil claim 1 , sodium lauryl glutamate claim 1 , disodium cocoamphodiacetate claim 1 , tyloxapol claim 1 , lauroyl macrogol-6 glycerides claim 1 , oleoyl macrogol-6 glycerides claim 1 , linoleoyl macrogol-6 glycerides claim 1 , propylene glycol monocaprylate claim 1 , propylene glycol monocaprylate claim 1 , propylene glycol monolaurate claim 1 , polyglyceryl-3 dioleate claim 1 , polyglyceryl-3 dioleate oleate claim 1 , triglycerides medium-chain claim 1 , propylene glycol dicaprylocaprate claim 1 , diethylene glycol monoethyl ether claim 1 , behenoyl polyoxyl-8 glycerides or PEGylated glyceryl behenate claim 1 , glyceryl behenate claim 1 , glyceryl dipalmitostearate claim 1 , glyceryl behenate E471 claim 1 , diethylene glycol monoethyl ether claim 1 , octylphenol ethoxylate claim 1 , sodium deoxycholate claim 1 , and a mixture of (i) refined soybean oil claim 1 , (ii) glyceryl distearate and (iii) polyglyceryl-3 dioleate.3. The composition of claim 1 , wherein the emulsifier is stearoyl macrogol-32 glycerides.4. The composition of claim 1 , wherein the weight ratio of temozolomide and emulsifier is from about 1:1 to about 3:1.5. The composition of claim 1 , wherein the weight ratio of temozolomide and emulsifier is from about 1.5:1 to about 2:1.6. The composition of claim 1 , wherein the ...

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Номер записи: 85
26-02-2015 дата публикации

COMBINATION THERAPY OF A TYPE II ANTI-CD20 ANTIBODY WITH AN ANTI-BCL-2 ACTIVE AGENT

Номер: US20150056186A1
Автор: Friess Thomas, Klein Christian, STREIN PAMELA, Umana Pablo
Принадлежит: Hoffmann-La Roche Inc.

The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and an anti-Bcl-2 active agent for the treatment of a patient suffering from cancer, particularly a CD20-expressing cancer. An aspect of the invention is a composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Another aspect of the invention is a kit comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent. Yet another aspect of the invention is a method for the treatment of a patient suffering from cancer comprising co-administering, to a patient in need of such treatment, a type II anti-CD20 antibody and an anti-Bcl-2 active agent. 1. A composition comprising a type II anti-CD20 antibody and an anti-Bcl-2 active agent.2. A composition according to claim 1 , wherein said type II anti-CD20 antibody has a ratio of the binding capacities to CD20 on Raji cells (ATCC-No. CCL-86) of said type II anti-CD20 antibody compared to rituximab of 0.3 to 0.63. A composition according to claim 1 , wherein said type II anti-CD20 antibody is a humanized B-Ly1 antibody.4. A composition according to claim 1 , wherein said type II anti-CD20 antibody has increased antibody dependent cellular cytotoxicity (ADCC).5. A composition according to claim 1 , wherein at least 40% of the oligosaccharides of the Fc region of said type II anti-CD20 antibody are non-fucosylated.6. A composition according to claim 1 , wherein said anti-Bcl-2 active agent is selected from the group consisting of Oblimersen claim 1 , SPC-2996 claim 1 , RTA-402 claim 1 , Gossypol claim 1 , AT-101 claim 1 , Obatoclax mesylate claim 1 , A-371191 claim 1 , A-385358 claim 1 , A-438744 claim 1 , ABT-737 claim 1 , AT-101 claim 1 , BL-11 claim 1 , BL-193 claim 1 , GX-15-003 claim 1 , 2-Methoxyantimycin A3 claim 1 , HA-14-1 claim 1 , KF-67544 claim 1 , Purpurogallin claim 1 , TP-TW-37 claim 1 , YC-137 and Z-24.7. A composition according to claim 1 , wherein said anti-Bcl-2 active agent is ...

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Номер записи: 86
10-03-2022 дата публикации

TREATMENT OF A DISEASE OF THE GASTROINTESTINAL TRACT WITH A CHEMOKINE/CHEMOKINE RECEPTOR INHIBITOR

Номер: US20220071894A1
Автор: Jones Mitchell Lawrence, LUO Allison, Singh Sharat, Stylli Harry, Wahl Christopher Loren
Принадлежит:

This disclosure features methods and compositions for treating diseases of the gastrointestinal tract with a chemokine/chemokine receptor inhibitor. 1383.-. (canceled)384. A method of treating a disease of the gastrointestinal (GI) tract in a subject , the method comprising:orally administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a chemokine/chemokine receptor inhibitor; andreleasing the pharmaceutical composition at a desired location in the GI tract of the subject;wherein the release of the pharmaceutical composition results in a concentration of the chemokine/chemokine receptor inhibitor in the GI tissue that is higher than the concentration of the chemokine/chemokine receptor inhibitor in the blood, serum, or plasma.385. The method of claim 384 , wherein the concentration of the chemokine/chemokine receptor inhibitor in the GI tissue is about 2 times claim 384 , about 3 times claim 384 , about 4 times claim 384 , about 5 times claim 384 , about 6 times claim 384 , about 7 times claim 384 , about 8 times claim 384 , about 9 times claim 384 , or about 10 times higher than the concentration of the chemokine/chemokine receptor inhibitor in the blood claim 384 , serum claim 384 , or plasma.386. The method of claim 384 , wherein the concentration of the chemokine/chemokine receptor inhibitor released at the desired location in the GI tract is 10% claim 384 , 25% claim 384 , 50% claim 384 , 75% claim 384 , 100% claim 384 , 200% claim 384 , 300% claim 384 , 400% claim 384 , 500% claim 384 , 1000% claim 384 , or 2000% greater than the concentration of chemokine/chemokine receptor inhibitor in plasma.387. The method of claim 384 , wherein the concentration Cof the chemokine/chemokine receptor inhibitor in the plasma of the subject is less than 1 μg/mL claim 384 , less than 0.3 μg/mL claim 384 , less than 0.1 μg/mL claim 384 , or less than 0.01 μg/mL.388. The method of claim 384 , wherein the amount of the chemokine/ ...

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Номер записи: 87
03-03-2016 дата публикации

MAST CELL MARKERS AND PREVENTION, DIAGNOSIS, AND THERAPY FOR CHRONIC PELVIC PAIN SYNDROME

Номер: US20160058756A1
Автор: Done Joseph, Klumpp David J., Rudick Charles, Schaeffer Anthony J., Thumbikat Praveen
Принадлежит:

The present invention provides compositions and methods for detection, diagnosis, treatment and/or prevention of chronic pelvic pain syndrome. In particular, the present invention provides biomarkers of chronic pelvic pain syndrome (e.g., mast cell markers (e.g., tryptase)), and/or inhibition of mast cell function (e g inhibition of MCP-1 and/or MIP-1α) to treat or prevent chronic pelvic pain syndrome. 1. A method for treating and/or preventing chronic pelvic pain syndrome in a subject , comprising administering therapeutic composition comprising a therapeutically effective amount of an inhibitor of mast cell function to said subject.2. The method of claim 1 , wherein said inhibitor of mast cell function comprises a combination of a mast cell stabilizer and a histamine receptor antagonist.3. The method of claim 2 , wherein said therapeutic composition further comprising one or more inhibitors of MCP-1 and/or MIP-1α.4. The method of claim 2 , wherein said histamine receptor antagonist comprises a histamine receptor 1 antagonist and/or histamine receptor 2 antagonist.5. A method for treating and/or preventing chronic pelvic pain syndrome in a subject claim 2 , comprising co-administering a mast cell stabilizer and a histamine receptor antagonist.6. The method of claim 5 , further comprising administering one or more inhibitors of MCP-1 or MIP-1α.7. A composition for the treatment or prevention of CPPS claim 5 , comprising:a) a mast cell stabilizer; andb) a histamine receptor antagonist.8. The composition of claim 7 , further comprising an inhibitor of a CPPS biomarker.9. The composition for the treatment or prevention of CPPS of claim 7 , wherein said histamine receptor antagonist comprises a histamine receptor 1 antagonist and/or a a histamine receptor 2 antagonist.10. The composition for the treatment or prevention of CPPS of claim 7 , comprising inhibitors of MIP-1α and/or MCP-1.11. A method for detecting chronic pelvic pain syndrome in a subject claim 7 , ...

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Номер записи: 88
03-03-2016 дата публикации

Treatment of Operable High-Grade Glioma With Sitimagene Ceradenovec Gene Therapy and Ganciclovir

Номер: US20160058888A1
Автор: Yla-Herttuala Seppo
Принадлежит: Gliotherapy Limited

Gene therapy with genes for prodrug converting enzymes adds to local control of glioblastoma achieved by surgery. There appears to be a pronounced local reaction which is in part inflammatory and has a measurable immunological component. Considering the widely proven fact that during the weekslong gap-phase between surgery and completion of radiation or chemoradiation tumour growth from the infiltrative zone may continue unhampered, a treatment such as SIT will cover that time period. 1. In a method of treating glioblastoma in a human by surgical resection and temozolomide , an improvement comprising:{'sup': '12', 'b. administering locally about the surgical resection site after surgical resection, about 1×10particles of replication-deficient adenovirus serotype 5 with E1 and partial E3 deletions, and containing the cDNA for HSV-tk which is able to phosphorylate ganciclovir, then'}c. administering gancyclovir 5 mg/kg i.v., twice daily.2. The method of claim 1 , where said glioblastoma is amenable to complete resection.3. The method of claim 1 , where said glioblastoma is neither bi-hemispheric nor multifocal.4. The method of claim 2 , where said glioblastoma is neither bi-hemispheric nor multifocal.5. The method of claim 1 , wherein said replication-deficient adenovirus is administered as a series of injections using a blunt needle advanced up to about 2 cm (tissue depth permitting).6. The method of claim 5 , entailing from about 30 to about 70 injections.7. The method of claim 5 , wherein said series of injections are into the wall of the resection cavity at the end of the complete resection.8. The method of claim 5 , wherein a plurality of said injections administer about 100 μl per injection site.9. The method of claim 5 , wherein a plurality of said injections administer sufficient adenovirus suspension to produce cavitations visible on MRI.10. The method of claim 1 , wherein said administering gancyclovir begins at least about five days after administering said ...

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Номер записи: 89
21-02-2019 дата публикации

METHODS OF TREATING CANCER USING COMPOSITIONS COMPRISING PERILLYL ALCOHOL DERIVATIVE

Номер: US20190054082A1
Автор: Chen Thomas
Принадлежит:

A method for treating brain metastases of a cancer in a mammal includes administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate, such as TMZ-POH. The brain metastases can be originated or spread from breast cancer. 1. A method for treating a brain metastasis of a cancer in a mammal , comprising administering to the mammal a therapeutically effective amount of a compound comprising perillyl alcohol (POH) conjugated with temozolomide (TMZ).2. The method of claim 1 , wherein the compound is 3-methyl 4-oxo-3 claim 1 ,4-dihydroimidazo[5 claim 1 ,1-d][1 claim 1 ,2 claim 1 ,3 claim 1 ,5]tetrazine-8-carbonyl)-carbamic acid-4-isopropenyl cyclohex-1-enylmethyl ester (TMZ-POH).3. The method of claim 1 , wherein the brain metastasis originates from a primary cancer selected from the group consisting of a systemic cancer claim 1 , lung cancer claim 1 , prostate cancer claim 1 , breast cancer claim 1 , hematopoietic cancer claim 1 , ovarian cancer claim 1 , bladder cancer claim 1 , germ cell tumors claim 1 , kidney cancer claim 1 , leukemia claim 1 , lymphoma claim 1 , and melanoma.4. The method of claim 3 , wherein the brain metastasis originates from breast cancer.5. The method of claim 1 , wherein the compound is administered by inhalation claim 1 , intranasally claim 1 , orally claim 1 , intravenously claim 1 , subcutaneously or intramuscularly.6. The method of claim 1 , wherein the administering comprises administering the compound intranasally using a nasal delivery device selected from the group consisting of an intranasal inhaler claim 1 , an intranasal spray device claim 1 , an atomizer claim 1 , a nebulizer claim 1 , a metered dose inhaler (MDI) claim 1 , a pressurized dose inhaler claim 1 , an insufflator claim 1 , a unit dose container claim 1 , a pump claim 1 , a dropper claim 1 , a nasal spray bottle claim 1 , a squeeze bottle and a bi-directional device.7. The method of claim 1 , further comprising treating the mammal with ...

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Номер записи: 90
04-03-2021 дата публикации

Cycloalkyl-Diamines for the Treatment of Inflammation

Номер: US20210060023A1
Автор: Godek Dennis Michael, Howard Harry Ralph, Stewart Andrew Morgan
Принадлежит: Medisynergics, LLC

The invention is directed to a method of treatment for inflammation in mammals including inflammation caused by bacterial or viral infection, the method comprising administering to a mammal, including a human, in need of such treatment a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof. 2. The method of wherein R4 is C-C-alkyl claim 1 , C-C-cycloalkyl or (CH)-R7 and wherein n is an integer between 0 and 6.3. The method of wherein R7 is selected from the group consisting of H claim 1 , C-C-alkyl claim 1 , C-C-cycloalkyl claim 1 , (C-C-alkyloxy)-(C-C-alkyl)- claim 1 , NR8R9-(C-C-alkyl)- claim 1 , aryl claim 1 , heterocyclyl and heteroaryl.4. The method of wherein said compound is selected from:{'sup': 1', '2, 'Cis-(1S, 2S)-1-(2-chlorophenyl)-N-methyl-N-[3-(pyrrolidin-1-yl)propyl]-cyclohexane-1,2-diamine trihydrochloride;'}{'sup': 1', '2, 'Trans-(1S, 2R)-1-(2-chlorophenyl)-N-methyl-N-[3-(pyrrolidin-1-yl)propyl]-cyclohexane-1,2-diamine trihydrochloride;'}{'sup': 2', '1, 'Cis-(1S, 2S)-1-(2-chlorophenyl)-N-[3-(4-fluorophenyl)propyl]-N-methyl-cyclohexane-1,2-diamine dihydrochloride;'}{'sup': 2', '1, 'Trans-(1S, 2R)-1-(2-chlorophenyl)-N-[3-(4-fluorophenyl)propyl]-N-methyl-cyclohexane-1,2-diamine dihydrochloride;'}{'sup': 1', '2, 'Cis-(1S, 2S)-1-(2-chlorophenyl)-N-methyl-N-(3-phenylpropyl)cyclohexane-1,2-diamine dihydrochloride;'}{'sup': 1', '2, 'Trans-(1S, 2R)-1-(2-chlorophenyl)-N-methyl-N-(3-phenylpropyl)cyclohexane-1,2-diamine dihydrochloride;'}{'sup': 2', '1, 'Cis-(1S, 2S)-1-(2-chlorophenyl)-N-(3,4-dimethoxyphenethyl]-N-methylcyclohexane-1,2-diamine dihydrochloride;'}{'sup': 2', '1, 'Trans-(1S, 2R)-1-(2-chlorophenyl)-N-(3,4-dimethoxyphenethyl]-N-methylcyclohexane-1,2-diamine dihydrochloride;'}{'sup': 1', '2, 'Cis-(1S, 2S)-1-(2-chlorophenyl)-N-methyl-N-(3-morpholinopropyl)cyclohexane-1,2-diamine trihydrochloride;'}{'sup': 1', '2, 'Trans-(1S, 2R)-1-(2-chlorophenyl)-N-methyl-N-(3-(morpholinopropyl)cyclohexane-1,2- ...

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Номер записи: 91
01-03-2018 дата публикации

METHODS OF TREATING MENINGIOMA

Номер: US20180057606A1
Автор: Burgess Antony Wilks, Cavenee Webster K., Collins Vincent Peter, Huang Huei-Jen Su, Johns Terrance Grant, Jungbluth Achim, Mark George, Murray Anne, Nice Edouard Collins, Old Lloyd J., Panousis Con, Renner Christoph, Ritter Gerd, SCOTT Andrew M., Stockert Elisabeth
Принадлежит:

The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to amplified epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof, is enhanced or evident upon aberrant post-translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof. 1. A method of treating a meningioma in a human subject , the method comprising administering to the subject a therapeutically effective amount of an isolated anti-Epidermal Growth Factor Receptor (EGFR) antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 164 , and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 166.2. The method according to claim 1 , wherein the heavy chain comprises the constant region set forth in SEQ ID NO: 43.3. The method according to claim 1 , wherein the light chain comprises the constant region set forth in SEQ ID NO: 48.4. The method according to claim 3 , wherein the antibody is an IgG isotype.5. The method according to claim 4 , wherein the IgG isotype is an IgG1 isotype.6. The method according to claim 1 , wherein the antibody is conjugated to a cytotoxic agent.7. The method according to claim 1 , wherein the antibody is administered in combination with temozolomide.8. A method of treating a meningioma in a human subject claim 1 , the method comprising administering to the subject a therapeutically effective amount of an isolated anti-Epidermal Growth Factor Receptor (EGFR) antibody claim 1 , wherein the antibody is capable of binding EGFR on tumors containing amplifications of ...

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Номер записи: 92
05-03-2015 дата публикации

COMBINATION THERAPY FOR THE TREATMENT OF GLIOBLASTOMA

Номер: US20150065781A1
Автор: Bais Carlos, BOURGON Richard, Phillips Heidi, SANDMANN Thomas
Принадлежит: Genentech, Inc.

This invention concerns methods of treating a patient diagnosed with glioblastoma comprising administering to said patient a therapy comprising an effective amount of an anti-VEGF antibody and a chemotherapeutic. 1. A method of treating a patient diagnosed with a glioblastoma comprising administering to said patient a therapy comprising an effective amount of an anti-VEGF antibody , an effective amount of a chemotherapeutic , and an effective amount of radiotherapy , wherein said treatment prolongs said patient's median overall survival time as compared to a glioblastoma patient receiving said chemotherapeutic without an anti-VEGF antibody.2. The method of claim 1 , wherein said patient has a WHO performance status of ≦2.3. The method of claim 1 , wherein the chemotherapeutic is temozolomide (TMZ).4. The method of claim 3 , wherein the TMZ is administered at 150 mg/m.5. The method of claim 3 , wherein the TMZ is administered at 200 mg/m.6. The method of claim 1 , wherein the radiotherapy is administered at 2 Gy.7. The method of claim 1 , wherein said anti-VEGF antibody binds the A4.6.1 epitope.8. The method of claim 1 , wherein said anti-VEGF antibody is bevacizumab.9. The method of claim 1 , wherein said anti-VEGF antibody comprises a variable heavy chain (VH) and a variable light chain (VL) claim 1 , wherein said VH has an amino acid sequence of SEQ ID NO: 2 and said VL has an amino acid sequence of SEQ ID NO: 1.10. The method of claim 1 , wherein said effective amount of said anti-VEGF antibody is 10 mg/kg intravenously every two weeks.11. The method of claim 1 , wherein said effective amount of said anti-VEGF antibody is 15 mg/kg intravenously every three weeks.12. The method of claim 1 , wherein said effective amount of said anti-VEGF antibody is administered initially intravenously over 90 minutes claim 1 , with subsequent infusions over 60 minutes and then 30 minutes.13. The method of claim 1 , wherein said anti-VEGF antibody is administered first to said ...

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Номер записи: 93
22-05-2014 дата публикации

CHEMICALLY AND METABOLICALLY STABLE DIPEPTIDE POSSESSING POTENT SODIUM CHANNEL BLOCKER ACTIVITY

Номер: US20140142118A1
Автор: JOHNSON Michael Ross
Принадлежит: PARION SCIENCES, INC.

A very stable, selective and renally safe sodium channel blocker represented by the formula: The invention also includes a variety of compositions, combinations and methods of treatment using this inventive sodium channel blocker. 2. The compound of claim 1 , which is an acid addition salt of an inorganic acid or an organic acid selected from the group consisting of hydrochloric acid claim 1 , hydrobromic acid claim 1 , sulfuric acid claim 1 , phosphoric acid claim 1 , nitric acid claim 1 , acetic acid claim 1 , oxalic acid claim 1 , tartaric acid claim 1 , succinic acid claim 1 , maleic acid claim 1 , furmaric acid claim 1 , gluconic acid claim 1 , citric acid claim 1 , malic acid claim 1 , ascorbic acid claim 1 , benzoic acid claim 1 , tannic acid claim 1 , palmitic acid claim 1 , alginic acid claim 1 , polyglutamic acid claim 1 , naphthalensulfonic acid claim 1 , methanesulfonic acid claim 1 , p-toluenesulfonic acid claim 1 , naphthalenedisulfonic acid claim 1 , polygalacturonic acid claim 1 , malonic acid claim 1 , sulfosalicylic acid claim 1 , glycolic acid claim 1 , 2-hydroxy-3-naphthoate claim 1 , pamoate claim 1 , salicylic acid claim 1 , stearic acid claim 1 , phthalic acid claim 1 , mandelic acid claim 1 , and lactic acid.3. A pharmaceutical composition claim 1 , comprising the compound of and a pharmaceutically acceptable carrier.4. A composition claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the compound of ; and'}a P2Y2 receptor agonist.5. A composition claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the compound of ; and'}a bronchodilator.6. A method of promoting hydration of mucosal surfaces claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering an effective amount of the compound of to a mucosal surface of a subject.'}7. A method of blocking sodium channels claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting sodium channels with an effective ...

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Номер записи: 94
27-02-2020 дата публикации

PHARMACEUTICAL COMPOSITION AND METHOD FOR ACUTE ON CHRONIC LIVER FAILURE AND RELATED LIVER DISEASES

Номер: US20200061053A1
Автор: Fang Ming
Принадлежит:

The present invention provides a composition and method for treating acute on chronical liver failure or a related disease. The method comprises administering to a subject a composition comprising trimetazidine dihydrochloride (1-[2,3,4-trimethoxybenzyl] piperazine dihydrochloride) (“TMZ”) according to a dosage regimen. 126-. (canceled)27. A method of treating a liver disorder or a related disease , comprising administering to a patient in need thereof a formulation , the formulation comprising (1-[2 ,3 ,4-trimethoxybenzyl] piperazine dihydrochloride) (“TMZ”) and a carrier , the formulation provides a release profile of the TMZ , which profile comprising a burst release of the TMZ followed by a sustained release of TMZ , wherein the burst release releases 30 mg to 180 mg of TMZ following administration of the TMZ.28. The method according to claim 27 , wherein the burst release releases 30 mg to 150 mg of TMZ within 30 minutes following administration of the TMZ to a patient.29. The method according to claim 27 , wherein the sustained release releases 10 mg to 30 mg of TMZ every 4 to 6 hours over a period from one day to one month.30. The method of claim 27 , wherein the liver disorder is acute on chronic liver failure.31. The method according to claim 27 , wherein the related disorder does not include angina pectoris claim 27 , coronary insufficiency claim 27 , previous myocardial infarction claim 27 , coronary heart disease claim 27 , vertigo or tinnitus.32. The method according to claim 27 , wherein the related disorder is selected from the group consisting of hepatopathy claim 27 , hepatitis claim 27 , and cirrhosis.33. The method according to claim 27 , wherein the related disorder is selected from the group consisting of viral hepatitis claim 27 , non-specific virus hepatitis claim 27 , drug or medication induced liver injury or damage claim 27 , toxin induced hepatitis or hepatopathy claim 27 , alcoholic hepatitis claim 27 , autoimmune hepatitis claim 27 , ...

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Номер записи: 95
08-03-2018 дата публикации

Pharmaceutical composition for treating posttraumatic stress disorder

Номер: US20180064707A1
Автор: BumJin Ko, Joo Han Lee, Joung-Hun Kim, Oh-Bin Kwon
Принадлежит: Academy Industry Foundation of POSTECH

Provided are a posttraumatic stress disorder (PTSD) animal model in which dopamine receptor subtype 4 (D4R) is damaged or deficient, a method for preparing the same, a method for screening a drug for treating PTSD using the same, and a pharmaceutical composition for treating PTSD comprising a drug detected by the screening method. As it is identified that a specific type of dopamine receptor is associated with a mechanism for fear memory expression induced by long-term depression (LTD), the understanding of pathogenesis of PTSD may be heightened, the animal model exhibiting similar clinical conditions of PTSD and the method for preparing the same may be applied in analyses for stability and effectiveness of a therapeutic agent for PTSD and screening of a therapeutic drug. Further, an agonist of D4R contained in the composition has been approved by the US FDA and clinically used for psychiatric diseases such as schizophrenia, and thus may be immediately used for clinical applications for PTSD symptoms.

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Номер записи: 96
11-03-2021 дата публикации

DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)

Номер: US20210069191A1
Автор: Chu Daniel, WANG Bing
Принадлежит:

A compound having the structure set forth in Formula (I) and Formula (II): 126-. (canceled)27. A method of treating lung cancer in a subject , comprising administering to the subject a therapeutically effective amount of 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1 ,2 ,4-triazol-5-yl)-8 ,9-dihydro-2H-pyrido[4 ,3 ,2-de]phthalazin-3(7H)-one , or a pharmaceutically acceptable salt or solvate thereof.28. The method of claim 27 , wherein said administration is in combination with ionizing radiation claim 27 , one or more chemotherapeutic agents claim 27 , or a combination thereof.29. The method of claim 28 , wherein the compound is used in combination with one or more chemotherapeutic agents claim 28 , wherein each chemotherapeutic agent is independently methyl methanesulfonate claim 28 , temozolomide claim 28 , dacarbazine (DTIC) claim 28 , a topoisomerase-1 inhibitor claim 28 , Topotecan claim 28 , Irinotecan claim 28 , Rubitecan claim 28 , Exatecan claim 28 , Lurtotecan claim 28 , Gimetecan claim 28 , Diflomotecan claim 28 , a homocamptothecin claim 28 , Doxorubicin claim 28 , a platinum based antineoplastic agent claim 28 , a 7-substituted non-silatecan claim 28 , a 7-silyl camptothecin claim 28 , paclitaxel claim 28 , cetuximab claim 28 , daunorubicin claim 28 , methotrexate claim 28 , a hormone claim 28 , an antiestrogen claim 28 , an antiandrogen claim 28 , a gonadotropin releasing hormone analog claim 28 , an interferon claim 28 , alpha interferon claim 28 , a tyrosine kinase inhibitor claim 28 , gefitinib claim 28 , imatinib claim 28 , gemtuzumab claim 28 , or BNP 1350.30. The method of claim 28 , wherein the compound is used in combination with one or more chemotherapeutic agents claim 28 , wherein each chemotherapeutic agent is independently irinotecan claim 28 , cisplatin claim 28 , carboplatin claim 28 , paclitaxel claim 28 , or temozolomide.31. The method of claim 27 , wherein the subject is a human.32. The method of claim 28 , wherein the subject is a ...

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Номер записи: 97
12-03-2015 дата публикации

TREATMENT OF MALE SEXUAL DYSFUNCTION

Номер: US20150072995A1
Автор: Naylor Alasdair Mark, Russell Rachel Jane, Street Stephen Derek Albert, Tang Kim-Wah, Van Der Graaf Pieter Hadewijn, Wayman Christopher Peter
Принадлежит: Ixchelsis Limited

A composition comprising a selective oxytocin antagonist for use in the treatment and/or prevention of a male ejaculatory disorder; which selective oxytocin antagonist is optionally admixed with a pharmaceutically acceptable carrier, diluent or excipient. 1. A pharmaceutical composition comprising a selective oxytocin antagonist admixed with a pharmaceutically acceptable carrier , diluent or excipient.2. (canceled)3. The pharmaceutical composition according to wherein the-selective oxytocin antagonist is at least 20-fold selective for an oxytocin receptor as compared with a vasopressin receptor.46.-. (canceled)7. A method of treating or preventing a male ejaculatory disorder in a human or animal which method comprises administering to a human or animal in need thereof an effective amount of a selective oxytocin antagonist; wherein said selective oxytocin antagonist is at least 20-fold selective for an oxytocin receptor as compared with a vasopressin receptor.8. The method according to wherein the male ejaculatory disorder is premature ejaculation.927.-. (canceled)28. A method of treating or preventing a male ejaculatory disorder in a human or animal which method comprises administering to a human or animal in need thereof a pharmaceutical composition comprising an effective amount of a selective oxytocin antagonist claim 7 , wherein the selective oxytocin antagonist is at least 20-fold selective for an oxytocin receptor as compared with a vasopressin receptor; and one or more PDE 5 inhibitors admixed with a pharmaceutically acceptable carrier claim 7 , diluent or excipient.2930.-. (canceled)31. The method according to claim 7 , wherein the selective oxytocin antagonist is admixed with a pharmaceutically acceptable carrier claim 7 , diluent or excipient.32. The method according to claim 8 , wherein administration of the selective oxytocin causes an increase in latency to ejaculation in the human or animal.33. The method according to claim 8 , wherein administration ...

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Номер записи: 98
29-05-2014 дата публикации

METHODS OF TREATING CANCER AND TESTING MUTATION ZYGOSITY RELATED THERETO

Номер: US20140147411A1
Автор: Hill Charles E., Pollack Brian Paul, Sapkota Bishu
Принадлежит:

In certain embodiments, the disclosure relates to methods of treating cancer comprising administering an effective amount a tyrosine kinase inhibitor in combination with an immunotherapy to a subject in need thereof. In certain embodiments, the disclosure relates to methods of treating cancer comprising: i) analyzing both chromosomes in a cell from a subject for the a V600E mutation of BRAF; and ii) determining if both of the chromosomes contain the V600E mutation, then treating the subject comprising the step of administering an effective amount a tyrosine kinase inhibitor in combination with an immunotherapy to the subject. 1. A method of treating cancer comprising:i) analyzing both chromosomes in a cell from a subject for the a V600E mutation of BRAF; andii) determining if both of the chromosomes contain the V600E mutation, then treating the subject comprising the step of administering an effective amount a tyrosine kinase inhibitor in combination with an immunotherapy to the subject.2. The method of claim 1 , wherein the cancer is melanoma.3. The method of claim 1 , wherein the tyrosine kinase inhibitor is vemurafenib claim 1 , PLX4720 claim 1 , sorafenib claim 1 , temozolomide claim 1 , or dabrafenib.4. The method of claim 1 , wherein the immunotherapy is administration of an interferon claim 1 , administration of an interleukin claim 1 , administration of an anti-PD1 antibody claim 1 , administration of an anti-CTLA-4 antibody claim 1 , a cancer vaccine claim 1 , or adoptive cell transfer.5. The method of claim 1 , wherein the interferon is human recombinant IFN-α claim 1 , IFN-α2b or IFN-γ or the interleukin is human recombinant IL-2.6. The method of claim 1 , further comprising the step of recording whether the subject is homozygous for the V600E mutation claim 1 , heterozygous for the V600E mutation claim 1 , heterozygous for the wild-type V at 600 claim 1 , or homozygous for the wild-type V at 600.7. The method of claim 1 , wherein the recording is on a ...

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Номер записи: 99
29-05-2014 дата публикации

USES OF NANOG INHIBITORS AND RELATED METHODS

Номер: US20140147440A1
Автор: Ruiz Altaba Ariel
Принадлежит: UNIVERSITE DE GENEVE

The present invention relates to substances and compositions thereof useful in the control of cancer stem cell persistence and concomitant tumor recurrence and/or control of tumor growth. In particular, the invention relates to substances and compositions useful in the treatment of cancers and/or tumors linked to cancer stem cells, preferably brain cancers and/or tumors, in a subject. 123-. (canceled)24. A NANOG antagonist consisting of a NANOG dominant-negative polypeptide comprising a NANOG homeodomain fused to the repressor domain of a heterologous protein.25. The NANOG antagonist according to claim 24 , wherein the NANOG homeodomain has the amino acid sequence SEQ ID NO: 5 or an amino acid sequence at least 80% identical to SEQ ID NO: 5 and binds to the DNA consensus sequence of SEQ ID NO: 34.26. The NANOG antagonist according to claim 24 , wherein the repressor domain of a heterologous protein is selected from the repressor domain of Pit-1beta (SEQ ID NO: 37) claim 24 , the repressor domain of an Engrailed protein selected from SEQ ID NO: 36 or 38 claim 24 , the repressor domain of IRF1 (SEQ ID NO: 39) claim 24 , and the WRPW motif of the hairy-related protein (SEQ ID NO: 44).27. The NANOG antagonist according to claim 24 , wherein the NANOG dominant-negative polypeptide further comprises a cell penetrating peptide for translocating the polypeptide across the cell membrane and/or a brain tumor targeting peptide.28. A pharmaceutical formulation comprising a NANOG antagonist according to and at least one pharmaceutically acceptable carrier.29. The pharmaceutical formulation according to further comprising a co-agent selected from bevacizumab claim 28 , temazolomide claim 28 , procarbazine claim 28 , carmustine claim 28 , or cilengitide.30. A method of preventing claim 28 , repressing or treating cancers and/or tumors linked to cancer stem cells in a subject claim 28 , said method comprising administering in a subject in need thereof a therapeutically effective ...

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Номер записи: 100