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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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Форма поиска

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 614. Отображено 100.
14-11-2013 дата публикации

Pharmacological vitreolysis

Номер: US20130302304A1
Автор: Marc De Smet, Steve Pakola
Принадлежит: THROMBOGENICS NV

A method of treating or preventing a disorder, or a complication of a disorder, of an eye of a subject comprising contacting a vitreous and/or aqueous humor with a composition comprising a truncated form of plasmin comprising a catalytic domain of plasmin (TPCD). TPCDs include, but are not limited to, miniplasmin, microplasmin and derivatives and variants thereof. The methods of the invention can be used to reduce the viscosity of the vitreous, liquefy the vitreous, induce posterior vitreous detachment, reduce hemorrhagic blood from the eye, clear or reduce materials toxic to the eye, clear or reduce intraocular foreign substances from the eye, increase diffusion of a composition administered to an eye, reduce extraretinal neovascularization and any combinations thereof. The method can be used in the absence of, or as an adjunct to, vitrectomy.

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Номер записи: 1
07-01-2016 дата публикации

COMPOSITIONS AND METHODS FOR TREATING COLLAGEN-MEDIATED DISEASES

Номер: US20160000889A1
Автор: Bassett Phillip J., Del Tito, Hitchcock Antony G., JR. Benjamin J., Sabatino Gregory L., Tharia Hazel A., Wegman Thomas L., Yu Bo
Принадлежит:

A drug product comprising a combination of highly purified collagenase I and collagenase II from is disclosed. The drug product includes collagenase I and collagenase II in a ratio of about 1 to 1, with a purity of greater than at least 95%. The invention further disclosed improved fermentation and purification processes for preparing the said drug product. 1Clostridium histolyticum. A drug product comprising isolated and purified collagenase I and collagenase II having the sequence of collagenase I and collagenase II , respectively , wherein the collagenase I and collagenase II have a mass ratio of about 1 to 1 and the drug product is at least 95% by area pure as determined by reverse phase high performance liquid chromatography.2. The drug product of claim 1 , wherein the drug product contains less than about 2% by area aggregated protein as determined by reverse phase high performance liquid chromatography.3. The drug product of claim 1 , wherein the drug product contains less than about 1% by area of clostripain as determined by reverse phase high performance liquid chromatography.4. The drug product of claim 1 , wherein the drug product contains less than about 1% by area of gelatinase as determined by anion exchange chromatography.5. The drug product of claim 1 , wherein the drug product contains less than about 1 ug/mg (w/w) of leupeptin.6. The drug product of claim 1 , wherein the drug product has a bioburden less than 1 cfu/ml claim 1 , and wherein the drug product is sterile.7. The drug product of claim 6 , wherein the drug product contains less than 10 EU/ml of endotoxin.8. The drug product of claim 6 , wherein the drug product contains less than 5 EU/mg of endotoxin.9Clostridium histolyticum. A drug product comprising isolated and purified collagenase I and collagenase II having the sequence of collagenase I and collagenase II claim 6 , respectively claim 6 , wherein the collagenase I and collagenase II have a mass ratio of about 1 to 1 and the drug ...

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Номер записи: 2
07-01-2016 дата публикации

Thermosensitive hydrogel collagenase formulations

Номер: US20160000890A1
Автор: Bo Yu, Thomas L. Wegman
Принадлежит: Biospecifics Technologies LLC

It is an object of the present disclosure to provide a formulation for injectable and topical collagenase, which will have extended residence time for the drug at the therapeutic targeted area for the indication being treated. It is a further object of the disclosure to provide a slow release formulation for collagenase, which is compatible with the active ingredient and does not adversely affect its activity. Still a further object of the disclosure is to provide an injectable formulation for collagenase which can be effectively administered to a patient with a small size needle without exhibiting pre-gelation, which would interfere with the ability to deliver the required dose for treatment. Still a further object of the disclosure is to provide a water-based topical formulation for collagenase which will be more compatible with other topically used medications to achieve better results.

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Номер записи: 3
14-01-2016 дата публикации

PHARMACEUTICAL COMPOUNDING KIT

Номер: US20160008777A1
Автор: Erkoboni David F., Patel Kunal, PATEL Piushbhai J., Patel Snehal, RODRIGUEZ Jeimy, SZEM Lyndsey Marie
Принадлежит:

A kit which is useful in the preparation of a compounded pharmaceutical product is provided. A method for using such a kit to make a compounded pharmaceutical product, and a compounded pharmaceutical product are also provided. Further provided is an apparatus for use in making a compounded pharmaceutical product. 1. A kit for use in the preparation of a compounded pharmaceutical product , said kit comprising an active agent container , wherein said kit is capable of producing compounded pharmaceutical products wherein the pharmaceutically active agent can be present in said product at various dosage strengths.2. The kit according to claim 1 , wherein said kit further comprises an inactive agent container associated with said active agent container.3. The kit according to claim 2 , wherein said kit further comprises a connector means.4. The kit according to claim 2 , wherein said active agent container or said inactive agent container is in the form of a media dispenser which is capable of drawing and dispensing a metered amount of the contents therein.5. The kit according to claim 2 , wherein said kit comprises at least two inactive agent containers with one being a non-base inactive container and another being a base container claim 2 , said non-base inactive container being in the form of a media dispenser.6. The kit according to wherein said inactive agent container and said active container are chambers within a multi-chambered pouch and wherein the barrier between said containers is frangible or contains a frangible element and said kit further comprises a recipient container which is capable of drawing and dispensing metered amounts of media.7. The kit according to claim 6 , wherein said kit comprises at least two inactive agent containers with one being a non-base inactive container contained in said pouch with said active container and another being a base container which is separate from said pouch.8. The kit according to claim 6 , further comprising a ...

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Номер записи: 4
14-01-2021 дата публикации

POLYPEPTIDE HAVING COLLAGENASE ACTIVITY AND METHOD FOR PRODUCING THE SAME

Номер: US20210009978A1
Автор: Aratake Masahiro
Принадлежит: KANEKA CORPORATION

One or more embodiments of the present invention provide a novel polypeptide that enables production of a highly uniform polypeptide having collagenase activity. The polypeptide of the one or more embodiments of the present invention is a mutant polypeptide comprising amino acid substitutions in collagenase G or collagenase H. The mutant polypeptide is not modified with an N-linked sugar chain when it is obtained via secretory production in an expression system using a yeast host. 1. A polypeptide comprising an amino acid sequence that is either (a1) or (a2):(a1) an amino acid sequence having 85% or higher sequence identity to an amino acid sequence set forth in SEQ ID NO: 1 or 2,(a2) an amino acid sequence derived from an amino acid sequence set forth in SEQ ID NO: 1 or 2 by substitution, deletion, and/or addition of 1 or a plurality of amino acid residues,wherein the polypeptide has collagenase activity, andwherein the amino acid sequence is either (c1) or (c2):(c1) the amino acid sequence according to (a1) or (a2) wherein all an amino acid residues corresponding to amino acids 149, 251, 330, 419, 704, 857, 915, 944, 966, 992, 1013, and 1026 in the amino acid sequence set forth in SEQ ID NO: 1 are resistant to N-glycosylated modification;(c2) the amino acid sequence according to (a1) or (a2) wherein all the amino acid residues corresponding to amino acids 89, 180, 514, and 601 in the amino acid sequence set forth in SEQ ID NO: 2 are resistant to N-glycosylated modification.3. A vector comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a polynucleotide comprising nucleotide sequences encoding the polypeptide according to ; and'}a signal peptide that enables secretion of the polypeptide from a yeast.4. A yeast comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a polynucleotide comprising nucleotide sequences encoding the polypeptide according to ; and'}a signal peptide that enables secretion of the polypeptide from the yeast. One or more ...

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Номер записи: 5
14-01-2021 дата публикации

Methods of Novel Therapeutic Candidate Identification Through Gene Expression Analysis in Vascular-Related Diseases

Номер: US20210010082A1
Автор: Mann David M.
Принадлежит:

Multiple treatment regimens for vascular-related diseases and disorders. Methods of treating vascular-related disorders based on gene expression studies from samples collected from individuals having symptoms of vascular-related disorders. Additionally, methods for diagnostic techniques to focus treatment regimens. Finally, methods of treating vascular-related disorders involving targeting microRNAs. 1. A method of diagnosing a vascular-related disease in an individual comprising the steps of: ["1) obtaining a biopsy sample from the individual's artery during progression of the vascular-related disease;", '2) obtaining an artery sample from a non-diseased control;', '3) extracting RNA from the samples in steps 1) and 2);', '4) obtaining gene products from the RNA extracted in steps 3); and', '5) comparing gene expression levels from the biopsy sample with the non-diseased control; and, 'a) identifying at least one gene that is upregulated or downregulated in the vascular-related disease comprising the steps ofb) associating the genes upregulated in the biopsy sample with an inhibitor of the gene products for administration to the individual and genes downregulated in the biopsy sample with a promoter of the gene products for administration to the individual.2. The method of claim 1 , wherein the vascular-related disease is pulmonary arterial hypertension.3. The method of claim 1 , wherein the biopsy sample is extracted using an endoarterial catheter.4. A method of identifying microRNA dysregulated in an individual having a vascular-related disease comprising the steps of:a) obtaining a biopsy sample from the individual's artery during progression of the vascular-related disease;b) obtaining an artery sample from a non-diseased control;c) extracting RNA from the samples in steps a) and b);d) converting the RNA to cDNA;e) comparing levels of microRNA expression from the biopsy sample with the non-diseased control; andf) identifying the microRNA dysregulated in the ...

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Номер записи: 6
10-01-2019 дата публикации

A Method for Quantifying Therapeutic Antibodies

Номер: US20190011455A1
Автор: Lebert Dorothée, Picard Guillaume
Принадлежит: Promise Advanced Proteomics

The present invention relates to a method for quantifying a therapeutic antibody in a sample of a human individual comprising a step of adding to a test sample which may contain therapeutic antibodies to be quantified a known amount of two or more labeled forms of said therapeutic antibodies. 1. A method for quantifying a therapeutic antibody in a sample of a human individual comprising the steps of:a) adding to a test sample which may contain therapeutic antibodies to be quantified a known amount of two or more labeled forms of said therapeutic antibodies, whereby a pre-proteolysis sample is provided,b) subjecting the pre-proteolysis sample to an enzyme proteolysis, so as to provide a proteolysis sample comprising (i) proteolysis labeled peptides derived from the labeled therapeutic antibodies and (ii) proteolysis peptides derived from the therapeutic antibody contained in the test sample,c) determining by mass spectrometric analysis the ratio between (i) one or more selected proteolysis labeled peptides and (ii) one or more corresponding proteolysis peptides derived from the said therapeutic antibody,d) calculating from the ratio determined at step c) the amount of the said therapeutic antibody in the test sample.2. The method according to claim 1 , for quantifying two or more therapeutic antibodies in said sample of a human individual.3. The method according to claim 1 , wherein the two or more therapeutic antibodies are selected in a group comprising Infliximab claim 1 , Etanercept claim 1 , Adalimumab claim 1 , Certolizumab and Golimumab.4. The method according to claim 1 , wherein the two or more therapeutic antibodies are selected in a group comprising Trastuzumab claim 1 , Rituximab and Bevacizumab.5. The method according claim 1 , wherein step b) comprises the following steps:b1) a step of enzyme proteolysis in denaturing conditions, andb2) a step of enzyme proteolysis in non-denaturing conditions.6. The method according to claim 1 , wherein enzyme ...

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Номер записи: 7
15-01-2015 дата публикации

PHARMACEUTICAL FORMULATIONS OF XANTHINE OR XANTHINE DERIVATIVES, AND THEIR USE

Номер: US20150017151A1
Автор: Buderer Matthew J.
Принадлежит:

The present invention relates to pharmaceutical formulations comprising xanthine or xanthine derivatives, kits thereof, and methods for treating fibrotic diseases by local administration. 2. The method of claim 1 , wherein R claim 1 , Rand Rare each claim 1 , independently claim 1 , H claim 1 , or optionally substituted C-Calkyl.3. The method of claim 1 , wherein R claim 1 , Rand Rare each claim 1 , independently claim 1 , H claim 1 , C-Calkyl claim 1 , or C-Calkyl substituted with acyl.4. The method of claim 1 , wherein the compound of formula I is a nonspecific phosphodiesterase inhibitor (PDEi).5. The method of claim 4 , wherein the nonspecific PDEi is pentoxifylline claim 4 , aminophylline claim 4 , enprofylline claim 4 , isbufylline claim 4 , theophylline claim 4 , theobromine claim 4 , or 3-isobutyl-1-methylxanthine (IBMX).6. The method of claim 4 , wherein the pharmaceutical formulation consists essentially of the therapeutically effective amount of the nonspecific PDEi or a pharmaceutically acceptable salt thereof.7. The method of claim 1 , wherein the compound of formula I is selected from the group consisting of pentoxifylline claim 1 , caffeine claim 1 , theophylline claim 1 , and aminophylline.8. The method of claim 1 , wherein the pharmaceutical formulation consists essentially of the therapeutically effective amount of pentoxifylline or a pharmaceutically acceptable salt thereof.9. The method of claim 1 , wherein the fibrotic disease is Peyronie's disease.10. The method of claim 1 , wherein administration of the formulation leads to improvement of erectile dysfunction.11. The method of claim 1 , wherein the pharmaceutical formulation has a pH of between 5.5 and 6.12. The method of claim 1 , wherein the therapeutically effective amount is between 4 mg and 20 mg.13. The method of claim 1 , wherein the pharmaceutical formulation is administered locally to the penis of the subject.14. The method of claim 13 , wherein the pharmaceutical formulation is ...

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Номер записи: 8
21-01-2021 дата публикации

COMPOSITIONS FOR REMODELING EXTRACELLULAR MATRIX AND METHODS OF USE THEREOF

Номер: US20210015907A1
Автор: SAGI Irit, SOLOMONOV Inna, ZEHORAI Eldar
Принадлежит: NanoCell Ltd.

The present invention relates to a method for increasing the embryo implantation rate in a mammalian uterus, by administering to the uterus of a mammal an effective amount of an extracellular matrix remodeling enzyme, as well as to a product comprising an extracellular remodeling enzyme. 1. A method ,wherein the method increases rate of embryo implantation in a uterus of a mammal, the method comprising:a. administering in an intrauterine manner at least one extra cellular matrix (ECM) remodeling enzyme selected from the group consisting of matrix metalloproteinase (MMP)-1 and MMP-13 to the mammal's uterus; andb. introducing at least one embryo into the treated uterus and allowing the introduced embryo to implant into an endometrium of the uterus.2. The method of claim 1 , wherein the at least one extra cellular matrix (ECM) remodeling enzyme is administered to the mammal's uterus at an amount sufficient to remodel an ECM of the endometrium of the uterus.3. The method of claim 1 , wherein the at least one extra cellular matrix (ECM) remodeling enzyme is administered to the mammal's uterus for a time sufficient to remodel an ECM of an endometrium of the uterus.4. The method of claim 1 , wherein the ECM remodeling enzyme is MMP-1.5. The method of claim 1 , wherein an amount sufficient to remodel an ECM of an endometrium of the uterus is from 0.1 to 10000 ng.6. The method of claim 1 , wherein a time sufficient to remodel an ECM of an endometrium of the uterus is from 10 minutes to 72 hours.7. The method of claim 1 , wherein the ECM remodeling enzyme is MMP-13.8. The method of claim 1 , wherein the uterus is a healthy uterus.9. The method of claim 1 , wherein said administering in an intrauterine manner is done with an intrauterine catheter.10. A method claim 1 , wherein the method increases rate of embryo implantation in a uterus of a mammal claim 1 , the method comprising: administering in an intrauterine manner at least one extra cellular matrix (ECM) remodeling ...

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Номер записи: 9
28-01-2021 дата публикации

Treatment Method and Product for Uterine Fibroids using Purified Collagenase

Номер: US20210023014A1
Автор: Phyllis Carolyn Leppert, Thomas L. Wegman
Принадлежит: Biospecifics Technologies LLC, Duke University

The invention relates to compositions and methods for treating uterine fibroids, wherein a uterine fibroid treatment agent comprising collagenase in an amount effective to cause shrinkage of uterine fibroids is injected or inserted into the uterine fibroid.

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Номер записи: 10
02-02-2017 дата публикации

REDUCED-PRESSURE TREATMENT SYSTEMS AND METHODS EMPLOYING DEBRIDEMENT MECHANISMS

Номер: US20170028037A1
Автор: Seegert Charles Alan, Wilkes Robert Peyton
Принадлежит:

Reduced-pressure treatment systems and methods are disclosed that employ debridement mechanisms to remove unwanted tissue. In one instance, a reduced-pressure treatment system for treating a tissue site on a patient includes a manifold member for distributing reduced pressure to the tissue site, a support member for disposing proximate the tissue site and the manifold, and a debridement mechanism coupled to the support member. The debridement mechanism is for debriding the tissue site. The system further includes a sealing drape for placing over the tissue site and manifold member. The sealing drape is operable to form a fluid seal over the tissue site and manifold member. The system also includes a reduced-pressure subsystem for delivering a reduced pressure to the sealing drape. The system may further include a chemical-debridement subsystem. Other systems, manifolds, and methods are disclosed. 119.-. (canceled)20. A method for treating a tissue site on a patient , the method comprising:placing a manifold member adapted to contract in response to application of reduce pressure proximate the tissue site, wherein the manifold member comprises a support member and a debridement arm having a proximal end and a distal end, the proximal end operatively coupled to the support member and the distal end having a face including an edge to debride the tissue site in response to contraction of the manifold member when induced by the application of reduced pressure;disposing a sealing drape over the manifold member and the patient's epidermis;forming a fluid seal between the sealing drape and the patient's epidermis to form a fluid seal over the tissue site and the manifold member; andproviding a reduced pressure to the manifold member whereby the debridement arm is deformable to drive the edge of the face against the tissue site in response to contraction of the manifold member.21. The method of claim 20 , further comprising introducing a debriding chemical to the tissue site ...

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Номер записи: 11
29-01-2015 дата публикации

Methods of Treating Serosal Cancer

Номер: US20150030583A1
Автор: Ertem Server A., Moore Malcolm A.S.
Принадлежит: SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH

The discovery of clonally pure populations of serosal cancer stem cells (CSCs) as well as methods of producing CSCs, culturing the CSCs and using them in screening assays, has lead to the development of methods of treating serosal and ovarian cancers by targeting removal or inhibition of the glycocalyx coat surrounding such cells, and includes combination therapies using particular chemotherapeutics in conjunction with glycocalyx inhibitors, as well as the same new chemotherapy treatments without targeting the glycocalyx, where the chemotherapeutic agent is any one of LBH-589 (Panobinostat), NVP-AUY922, LAQ824 (NVP-LAQ824, Dacinostat), colchicine, brefeldin A, diphenyleneiodonium chloride, any combination thereof or another agent identified herein. These treatment methods of the invention can also be used in combination with radiation treatment or other conventional cancer therapy. 110-. (canceled)11. A method to treat serosal cancer in a patient undergoing chemotherapy which comprises administering a hyaluronan synthase inhibitor , a hyaluronidase , a collagenase , or a combination thereof , for a time and in an amount to augment said chemotherapy , or to improve or increase patient survival time , or to cause remission of symptoms ,wherein said chemotherapy comprises administering an effective amount of a compound selected from the group consisting LBH-589 (Panobinostat), NVP-AUY922, LAQ824 (NVP-LAQ824, Dacinostat), colchicine, brefeldin A and diphenyleneiodonium chloride, or a combination thereof, to the patient.12. The method of claim 11 , wherein any one of said hyaluronan synthase inhibitor claim 11 , hyaluronidase or collagenase is PEGylated or otherwise modified to increase its half life in vivo.13. The method of claim 11 , wherein said administering a hyaluronan synthase inhibitor claim 11 , a hyaluronidase claim 11 , a collagenase claim 11 , or a combination thereof claim 11 , is done before claim 11 , concurrently with claim 11 , overlapping or after said ...

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Номер записи: 12
17-02-2022 дата публикации

CHEMICAL SCALPEL

Номер: US20220047687A1
Автор: BARAMBIO BUENDÍA Javier Jesús, CORTÉS GUIRAL Delia, GARCÍA ARRANZ Mariano, GARCÍA OLMO Damián, GUADALAJARA LABAJO Héctor, OLMEDILLAS LÓPEZ Susana, VEGA CLEMENTE Mª Luz
Принадлежит:

The present invention relates to a liquid collagenase solution which will generate the pre-conditioning of the tissues covering peritoneal tumors by means of washing with said solution for a predetermined time and at a predetermined concentration for use as cytotoxic drug-enhancing or adjuvant treatment in the treatment of solid peritoneal tumors. Throughout the present invention, said solution will be used for administration to or for irrigating the tumor directly at a concentration and for a time such that it causes thinning of the mesothelial layer covering the intestinal tract without the involvement of intermediate or internal layers. 1. A composition comprising collagenase in solution or suspension for use as cytotoxic drug-enhancing or adjuvant treatment in the treatment of solid peritoneal tumors , wherein said composition comprising collagenase is administered prior to cytotoxic treatment , being administered to or irrigating the tumor directly , and wherein said cytotoxic drug is mitomycin.2. The composition for use according to claim 1 , wherein said cytotoxic drug is administered to or irrigates the tumor directly claim 1 , and wherein said composition comprising collagenase is administered prior to cytotoxic treatment claim 1 , being administered to or irrigating the tumor directly.3. The composition for use according to claim 2 , wherein said composition is administered to or irrigates the tumor directly at a concentration and for a time such that it causes exposure of the tumor tissue without the involvement of any organ.4. The composition for use according to or claim 2 , wherein the action of the collagenase is inhibited by a collagenase inhibitor claim 2 , such as collagen claim 2 , being administered to or irrigating the tumor directly claim 2 , prior to administration of the cytotoxic drug.5. The composition for use according to any of to claim 2 , wherein tumors are selected from the list consisting of peritoneal adenocarcinomas or carcinomas.6. ...

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Номер записи: 13
01-02-2018 дата публикации

METHODS FOR TREATING AGING AND SKIN DISORDERS USING NUCLEIC ACIDS TARGETING TYR OR MMP1

Номер: US20180030451A1
Автор: Cauwenbergh Gerard
Принадлежит: RXi Pharmaceuticals Corporation

The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal applications. 1. A method for treating a skin disorder comprising administering to a subject in need thereof a therapeutically effective amount of a nucleic acid molecule that is directed against a gene encoding Matrix metalloproteinase-1 (MMP1) , tyrosinase (TYR) or prostaglandin-endoperoxide synthase 2 (PTGS2) , optionally wherein the nucleic acid molecule is a chemically modified oligonucleotide.23-. (canceled)4. The method of claim 1 , wherein the nucleic acid molecule is an isolated double stranded nucleic acid molecule that includes a double stranded region and a single stranded region claim 1 , wherein the region of the molecule that is double stranded is from 8-15 nucleotides long claim 1 , wherein the guide strand contains a single stranded region that is 4-12 nucleotides long claim 1 , wherein the single stranded region of the guide strand contains 3 claim 1 , 4 claim 1 , 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 claim 1 , 9 claim 1 , 10 claim 1 , 11 or 12 phosphorothioate modifications claim 1 , and wherein at least 40% of the nucleotides of the isolated double stranded nucleic acid molecule are modified.5. The method of claim 4 , wherein the isolated double stranded nucleic acid molecule further comprises a hydrophobic conjugate that is attached to the isolated double stranded nucleic acid molecule.6VibrioClostridium. The method of claim 1 , wherein the skin disorder is skin photo aging claim 1 , acne scarring claim 1 , cutaneous hyperpigmentation claim 1 , melasma claim 1 , skin lentigos claim 1 , chronic ulcers claim 1 , venous ulcers claim 1 , gangrene (and ) claim 1 , blistering skin disorders claim 1 , Stevens-Johnson syndrome claim 1 , or keloids.710-. (canceled)11. The method of claim 1 , wherein the nucleic acid molecule is in a composition formulated for topical delivery claim 1 , a composition ...

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Номер записи: 14
24-02-2022 дата публикации

Decellularization of Plant Cell Culture Materials for Tissue Engineering and Drug Delivery

Номер: US20220054710A1
Автор: Coburn Jeannine, Gaudette Glenn, Phan Nhi
Принадлежит:

Provided herein are enzymatically decellularized cells, and methods of producing said cells, that can be used in a scaffold. The scaffolds featured herein are biocompatible and can comprise decellularized cells that have been modified to express a bioactive agent or molecule. 1. A method for decellularizing cells , the method comprising:contacting a plurality of cells with a composition comprising a nuclease, thereby decellularizing the plurality of cells, wherein the plurality of cells are cellulose producing cells.2. The method of claim 1 , wherein the nuclease is DNasel.3. The method of claim 1 , wherein the plurality of cells are plant cells.4. The method of further comprising culturing the plurality of cells prior to contacting the cells with the nuclease.5. The method of claim 1 , further comprising isolating cellular material from the cultured plurality of cells.6. A scaffold comprising decellularized cells derived from a cellulose producing organism and a bioactive molecule.7. The scaffold of claim 6 , wherein the bioactive molecule is attached to the decellularized cells.8. The scaffold of claim 6 , wherein the decellularized cells are enzymatically decellularized plant-derived cells.9. The scaffold of claim 6 , wherein the bioactive molecule is VEGF claim 6 , bFGF claim 6 , IL-2 claim 6 , or a molecule that directs mammalian cell expansion claim 6 , differentiation claim 6 , or a cellular response.10. The scaffold of claim 6 , wherein the decellularized cells are cultured cells.1113.-. (canceled)14. A method of producing a biocompatible scaffold claim 6 , the method comprising:contacting the cellulose producing cells with a composition comprising a nuclease, thereby producing decellularized cells; andcreating a scaffold from the decellularized modified cells.15. The method of further comprising modifying the cellulose producing cells to express a bioactive agent.16. The method of claim 14 , wherein the bioactive agent is a molecule that directs mammalian ...

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Номер записи: 15
19-02-2015 дата публикации

Methods For Extracting A Tooth

Номер: US20150050617A1
Автор: Gafni Yosef, Marynka Kalmani Keren, Weinberg Evgeny
Принадлежит:

Methods of extracting teeth involving contacting, prior to extraction, the tissue surrounding a tooth to be extracted with a composition providing an agent capable of destroying the periodontal ligament surrounding the tooth, such as, collagenase. 1. A method for extracting a tooth in a subject in need thereof , the method comprising the steps of:a) applying a composition comprising an effective amount of an agent into the tissue surrounding said tooth, wherein the agent is an enzyme capable of destroying the periodontal ligament surrounding the tooth; andb) extracting said tooth from the subject.2. The method of claim 1 , wherein destroying the periodontal ligament surrounding the tooth comprises cleaving or hydrolyzing peptide bonds at the periodontal ligament surrounding the tooth.3. The method of claim 1 , wherein the step of extracting said tooth further comprises applying an extraction force parallel to the long axis of said tooth.4. The method of claim 3 , wherein the step of extracting said tooth is devoid of applying a rotational force.5. The method of claim 1 , wherein the step of applying a composition comprises contacting at least one locus at the periodontal ligament space surrounding the tooth.6. The method of claim 1 , wherein the step of applying a composition comprises injecting said composition into the intra periodontal ligament.7. The method of claim 1 , wherein the step of extracting said tooth is performed within 15 minutes to 3 hours after applying said composition.8. The method of claim 2 , wherein the agent is a proteolytic enzyme.9. The method of claim 8 , wherein the enzyme is collagenase.10. The method of claim 9 , wherein the collagenase is selected from the group consisting of collagenase I claim 9 , collagenase II claim 9 , collagenase III and a combination thereof.11. The method of claim 1 , wherein said composition has an effective volume of 0.01 to 3 ml.12. The method of claim 1 , wherein said subject is afflicted with a bleeding ...

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Номер записи: 16
25-02-2016 дата публикации

MATRIX METALLOPROTEINASSES AND USES THEREOF

Номер: US20160053250A1
Автор: FIELDS Gregg B., Zylberberg Claudia
Принадлежит:

Matrix metalloproteinases (MMPs) compositions, inactive forms of MMPs (e.g. proMMPs), fragments, mutants, variants or combinations thereof. A pharmaceutical composition comprises one or more of the above in a pharmaceutical carrier. A composition comprises at least one of: a matrix metalloproteinase (MMP), an inactive MMP or a proenzyme (proMMP) thereof, wherein the matrix metalloproteinase (MMPs), inactive MMPs or proMMPs thereof, comprise: MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13.MMP-14, MMP-15, MMP-16, MMP-17, MMP-18, MMP-19, MMP-20, MMP-21, MMP-23A, MMP-23B, MMP-24, MMP-25, MMP-26, MMP-27, MMP-28, active fragments, mutants, variants or any combinations thereof. The uses include isolation of cells, in particular stem cells, from tissues, dissociation of tissues, proteins and treatment of a variety of conditions. 1. A composition comprising at least one: a matrix metalloproteinase (MMP) , an inactive MMP or a proenzyme (proMMP) thereof , wherein the matrix metalloproteinase (MMPs) , inactive MMPs or proMMPs thereof , comprise: MMP-1 , MMP-2 , MMP-3 , MMP-7 , MMP-8 , MMP-9 , MMP-10 , MMP-11 , MMP-12 , MMP-13 , MMP-14 , MMP-15 , MMP-16 , MMP-17 , MMP-18 , MMP-19 , MMP-20 , MMP-21 , MMP-23A , MMP-23B , MMP-24 , MMP-25 , MMP-26 , MMP-27 , MMP-28 , active fragments , mutants , variants or any combinations thereof.2. The composition of claim 1 , wherein the MMP claim 1 , the inactive MMP or a proenzyme (proMMP) comprise: proteins claim 1 , peptides claim 1 , polypeptides claim 1 , nucleic acid sequences claim 1 , cDNA claim 1 , ribonucleic acid sequences claim 1 , chimeric molecules claim 1 , peptidomimetics claim 1 , peptide nucleic acids (PNA) claim 1 , or combinations thereof.3. The composition of claim 1 , wherein the composition further comprises a pharmaceutically acceptable agent claim 1 , a pharmaceutically acceptable salt or prodrug thereof.4. The composition of claim 1 , wherein the composition optionally comprises at least one ...

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Номер записи: 17
26-02-2015 дата публикации

NEW PROCESS FOR THE PRODUCTION AND PURIFICATION OF THE COLLAGENASE ENZYME FROM VIBRIO ALGINOLYTICUS

Номер: US20150056179A1
Автор: CAPUTO Michele, CUPPARI Christian, Gennari Giovanni, VACCARO Susanna
Принадлежит: FIDIA FARMACEUTICI S.p.A.

The present invention claims a novel process for the production and purification of microbial collagenase (Microbial Collagenase EC 3.4.24.3) produced by the non-pathogenic aerobic bacterium chemovar. (NCIMB Number: 1 1038, synonym LMG 3418, hereinafter called ), which said process provides high production levels of collagenase with a stable, reproducible, cheap fermentation process. The collagenase produced from according to the process described herein also presents a specific activity superior to that of other microbial collagenases, is stable in aqueous solution, and can be frozen without significant damage. A further subject of the present invention is pharmaceutical compositions containing collagenase obtained according to the production and purification process described, for the purpose of therapeutic treatment of disorders characterised by collagen accumulation or for the treatment of blemishes/imperfections that benefit from reducing local collagen accumulations. 1Vibrio alginolyticusIophagus. A process for the production and purification of collagenase from chemovar. , comprising the following stages:{'i': Vibrio Alginolyticus', 'Iophagus, 'Stage A: Inoculation of chemovar. into an Erlenmeyer flask and fermentation with culture broth of non-bovine animal origin;'}Stage B: Clarification of the fermented broth thus obtained by tangential flow ultrafiltration with 100-500 kD Molecular Weight Cut-Off (MWCO) cassettes, preferably 300 kD;Stage C: Dialysis and concentration of the clarified medium obtained in stage B, by tangential flow ultrafiltration with 5-30 kD MWCO cassettes, preferably 10 kD MWCO;Stage D: Purification of the solution containing collagenase obtained in Stage C, by anion-exchange resin carrying weak basic groups, at a pH of between 6.9 and 7.4, preferably at a pH of 7.1;Stage E: Dialysis and concentration of the fractions with collagenolytic activity collected in Stage D, by tangential flow ultrafiltration with 10-50 kD MWCO cassettes, ...

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Номер записи: 18
04-03-2021 дата публикации

COLLAGENASE LOADED LIPOSOMES FOR ENHANCING DRUG DELIVERY

Номер: US20210059936A1
Автор: Schroeder Avi, ZINGER Assaf
Принадлежит:

Pharmaceutical compositions comprising at least one lipid-based particle encapsulating a proteolytic enzyme and a pharmaceutically acceptable carrier, wherein the proteolytic enzyme comprises at least 75% proteolytically active enzyme are provided. Methods of using same and producing same are also provided. 1. A pharmaceutical composition comprising at least one lipid-based particle encapsulating at least one proteolytic enzyme and a pharmaceutically acceptable carrier , wherein at least 75% of said proteolytic enzyme is proteolytically active.2. The pharmaceutical composition of claim 1 , wherein said carrier is substantially devoid of ions that activate said proteolytic enzyme claim 1 , said proteolytic enzyme is dissolved in an aqueous solution devoid of ions that activate said proteolytic enzyme or both.3. The pharmaceutical composition of claim 1 , wherein said lipid-based particle is a liposome claim 1 , comprises a maximum cross-sectional area of less than 70 square microns or both.4. The pharmaceutical composition of claim 3 , wherein said liposome comprises between 50 and 60% DMPC claim 3 , 35 and 45% cholesterol and 3 and 7% 1 claim 3 ,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-PEG (PEG-DSPE).5. (canceled)6. The pharmaceutical composition of claim 2 , wherein said solution comprises a pH of 8 or above.7. The pharmaceutical composition of claim 1 , wherein said proteolytic enzyme is active against collagen claim 1 , is selected from collagenase claim 1 , papain and bromelain claim 1 , or both.8. (canceled)9. The pharmaceutical composition of claim 7 , wherein said proteolytic enzyme is collagenase.10. The pharmaceutical composition of claim 9 , wherein said collagenase is collagenase I claim 9 , collagenase II or both.11. (canceled)12. A method of decreasing fibrosis in a subject in need thereof claim 1 , the method comprising administering to said subject the pharmaceutical composition of claim 1 , thereby decreasing fibrosis in said subject ...

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Номер записи: 19
04-03-2021 дата публикации

THERMOSENSITIVE HYDROGEL COLLAGENASE FORMULATIONS

Номер: US20210060143A1
Автор: Wegman Thomas L., Yu Bo
Принадлежит: BioSpecifics Technologies Corp.

It is an object of the present disclosure to provide a formulation for injectable and topical collagenase, which will have extended residence time for the drug at the therapeutic targeted area for the indication being treated. It is a further object of the disclosure to provide a slow release formulation for collagenase, which is compatible with the active ingredient and does not adversely affect its activity. Still a further object of the disclosure is to provide an injectable formulation for collagenase which can be effectively administered to a patient with a small size needle without exhibiting pre-gelation, which would interfere with the ability to deliver the required dose for treatment. Still a further object of the disclosure is to provide a water-based topical formulation for collagenase which will be more compatible with other topically used medications to achieve better results. 1. A composition for treating a collagen-mediated disease , comprising collagenase and a carrier that provides sustained release of an amount of said collagenase sufficient to treat said collagen-mediated disease.2. The composition of claim 1 , wherein said carrier comprises gel-forming polymers.3. The composition of claim 2 , wherein said polymer is a triblock polymer or a copolymer based on N-siopropylacrylamide (NIPAAm)4. The composition of claim 3 , wherein said triblock polymers comprise poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG).5. The composition of claim 4 , wherein said polymers comprise a copolymer formed from PLGA and polyethylene glycol (PEG).6. The composition of claim 5 , wherein the PLGA and PEG copolymers are formed in repetitions of PLGA-PEG-PLGA or PEG-PLGA-PEG.7. The composition of claim 1 , wherein said composition is injectable claim 1 , insertable or applied topically.8. The composition of claim 1 , which can be administered through a syringe fitted with a 28G1/2 needle without pre-gelation in the needle on injection.9. The composition ...

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Номер записи: 20
20-02-2020 дата публикации

AGENTS AND METHODS FOR TREATING AND PREVENTING SEBORRHEIC KERATOSIS

Номер: US20200056151A1
Автор: Lee Sam W., Mandinova Anna I., Neel Victor A.
Принадлежит: The General Hospital Corporation

Provided herein are methods and assays for isolating and culturing seborrheic keratosis cells ex vivo. Also provided herein are screening assays using cultured seborrheic keratosis cells and methods for treating seborrheic keratosis in a subject. 1. A method for inducing apoptosis in a seborrheic keratosis cell , the method comprising contacting a seborrheic keratosis cell with a composition comprising an effective amount of an ATP-competitive Akt inhibitor , thereby inducing apoptosis in the cell.2. The method of claim 1 , wherein the effective amount of the ATP-competitive Akt inhibitor or the composition does not substantially affect the survival of normal keratinocytes.34.-. (canceled)5. The method of claim 1 , wherein the ATP-competitive Akt inhibitor is A-443654 claim 1 , AT7867 claim 1 , or GSK690693.6. A method for treating a seborrheic keratosis in a subject claim 1 , the method comprising administering a composition comprising a therapeutically effective amount of an ATP-competitive Akt inhibitor to a subject having seborrheic keratosis.7. The method of claim 6 , wherein the composition is applied topically or administered systemically.8. The method of claim 6 , wherein the therapeutically effective amount of the ATP-competitive Akt inhibitor or the composition does not substantially affect the survival or normal keratinocytes.9. The method of claim 6 , wherein the composition further comprises a pharmaceutically acceptable carrier.1012.-. (canceled)13. The method of claim 6 , further comprising a step of diagnosing the subject with a seborrheic keratosis.14. The method of claim 6 , wherein the ATP-competitive Akt inhibitor is A-443654 claim 6 , AT7867 claim 6 , or GSK690693. This application is a Continuation of U.S. application Ser. No. 16/029,892, filed Jul. 9, 2018, which is a continuation of U.S. application Ser. No. 15/482,899 filed on Apr. 10, 2017, which is a continuation of U.S. application Ser. No. 15/254,344 (now U.S. Pat. No. 9,658,210), filed ...

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Номер записи: 21
05-03-2015 дата публикации

PHARMACOLOGICAL VITREOLYSIS

Номер: US20150064161A1
Автор: DE SMET Marc, PAKOLA Steve
Принадлежит:

A method of treating or preventing a disorder, or a complication of a disorder, of an eye of a subject comprising contacting a vitreous and/or aqueous humor with a composition comprising a truncated form of plasmin comprising a catalytic domain of plasmin (TPCD). TPCDs include, but are not limited to, miniplasmin, microplasmin and derivatives and variants thereof. The methods of the invention can be used to reduce the viscosity of the vitreous, liquefy the vitreous, induce posterior vitreous detachment, reduce hemorrhagic blood from the eye, clear or reduce materials toxic to the eye, clear or reduce intraocular foreign substances from the eye, increase diffusion of a composition administered to an eye, reduce extraretinal neovascularization and any combinations thereof. The method can be used in the absence of, or as an adjunct to, vitrectomy. 1. A method of treating a vitreoretinal disease or disorder , or of treating a complication of a vitreoretinal disease or disorder , of an eye of a subject , comprising contacting the aqueous humor in the eye of the subject with an effective amount of a microplasmin and with an effective amount of a second agent other than microplasmin , thereby treating the vitreoretinal disease or disorder , or the complication of the vitreoretinal disease or disorder , of the eye of the subject.2. The method according to wherein said aqueous humor is contacted with the second agent prior to claim 1 , at the same time as claim 1 , or after being contacted with said microplasmin.3. The method according to wherein the second agent is a protein other than said microplasmin claim 1 , a chemical claim 1 , or another substance useful in treating or preventing an eye disorder or a complication of an eye disorder.4. The method according to wherein said second agent is selected from the group consisting of hyaluronidase claim 1 , chondroitinase ABC claim 1 , chondroitinase AC claim 1 , chondroitinase B claim 1 , chondroitin 4-sulfatase claim 1 , ...

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Номер записи: 22
05-03-2015 дата публикации

BMP Peptides & Methods of Use

Номер: US20150064163A1
Автор: James Clagett, Jingsong Chen, Silvia Chen, Xiaofei Qin
Принадлежит: LifeNet Health

The invention relates to truncated growth factors and variants thereof. The invention also relates to methods of making and using the truncated growth factors. The invention further relates to compositions including a protease and a growth factor comprising a bone morphogenic protein (BMP) or a variant thereof. The invention also relates to methods of using the composition.

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Номер записи: 23
05-03-2015 дата публикации

DEVICES AND METHODS FOR REDUCING THE APPEARANCE OF CELLULITE

Номер: US20150064165A1
Автор: Avelar Rui, Dominguez Zackary, Kayda Edwin, Perry Tracy Ann, Schwab Justin
Принадлежит:

Methods and devices for use in reducing the appearance of dimpled skin or other undesirable appearance of skin in a cellulitic region of a patient are provided. The methods include the steps of disrupting fibrous septae located beneath the skin of a cellulitic region and introducing a composition beneath the skin, the composition being effective to reduce or prevent regrowth of the fibrous septae. 1. A method for reducing the appearance of dimpled skin or other undesirable appearance of skin in a cellulitic region of a patient , the method comprising the steps ofdisrupting fibrous septae located beneath the skin of the cellulitic region; andintroducing a composition beneath the skin of the cellulitic region, the presence of the introduced composition being effective to reduce or prevent regrowth of the disrupted fibrous septae.2. The method of wherein the step of disrupting comprises introducing an enzyme effective to digest the septae.3. The method of wherein the composition comprises a hyaluronic acid gel.4. The method of wherein the composition further comprises an active agent.5. The method of wherein the active agent is an enzyme.6. The method of wherein the step of disrupting comprising introducing a cannula beneath skin of the cellulitic region.7. The method of wherein the cannula has blade effective to sever the septae.8. The method of wherein the cannula comprises a disrupting element comprising a tube having an aperture set apart from a distal tip of the tube claim 6 , the aperture including a sharp beveled edge.9. A device for reducing the appearance of cellulite in a patient claim 6 , the device comprising:a handpiece; a disrupting element configured and effective to cause disruption of fibrous septae in the cellulitic region, and', 'a cannula for introducing a composition into the cellulitic region to create separation between tissue planes and reduce or prevent regrowth of the fibrous septae., 'an assembly couplable to the handpiece and including ...

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Номер записи: 24
27-02-2020 дата публикации

Decellularization of Plant Cell Culture Materials for Tissue Engineering and Drug Delivery

Номер: US20200061245A1
Автор: Coburn Jeannine, Gaudette Glenn, Phan Nhi
Принадлежит:

Provided herein are enzymatically decellularized cells, and methods of producing said cells, that can be used in a scaffold. The scaffolds featured herein are biocompatible and can comprise decellularized cells that have been modified to express a bioactive agent or molecule. 1. A method for decellularizing cells , the method comprising:contacting a plurality of cells with a composition comprising a nuclease, thereby decellularizing the plurality of cells, wherein the plurality of cells are cellulose producing cells.2. The method of claim 1 , wherein the nuclease is DNaseI.3. The method of claim 1 , wherein the plurality of cells are plant cells.4. The method of further comprising culturing the plurality of cells prior to contacting the cells with the nuclease.5. The method of claim 1 , further comprising isolating cellular material from the cultured plurality of cells.6. A scaffold comprising decellularized cells derived from a cellulose producing organism and a bioactive molecule.7. The scaffold of claim 6 , wherein the bioactive molecule is attached to the decellularized cells.8. The scaffold of claim 6 , wherein the decellularized cells are enzymatically decellularized plant-derived cells.9. The scaffold of claim 6 , wherein the bioactive molecule is VEGF claim 6 , bFGF claim 6 , IL-2 claim 6 , or a molecule that directs mammalian cell expansion claim 6 , differentiation claim 6 , or a cellular response.10. The scaffold of claim 6 , wherein the decellularized cells are cultured cells.11. An enzymatically decellularized cell derived from a cellulose producing organism comprising a bioactive molecule.12. The enzymatically decellularized cell of claim 11 , wherein the cell is a cultured cell.13. The enzymatically decellularized cell of claim 11 , wherein the cellulose producing organism is a plant.14. A method of producing a biocompatible scaffold claim 11 , the method comprising:contacting the cellulose producing cells with a composition comprising a nuclease, ...

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Номер записи: 25
17-03-2016 дата публикации

PHARMACEUTICAL COMPOSITION BASED ON CENTELLA ASIATICA (HYDROCOTYLE ASIATICA L.) FOR THE TREATMENT OF LOWER LIMB ULCERS

Номер: US20160074454A1
Автор: MONTAÑEZ-SOTO Flor Lucía
Принадлежит:

A pharmaceutical composition based on (L.) for the treatment of lower limb ulcers, including as active ingredients, and sodium acexamate in amounts producing a reciprocal synergistic effect when mixed with at least one adjuvant selected from a healing agent, an antibiotic agent and/or combinations thereof is described. 1centella asiaticaHydrocotyle asiaticacentella asiatica. A pharmaceutical composition based on (L.) for the treatment of lower limb ulcers , characterized by comprising , as active ingredients , and sodium acexamate in amounts producing a reciprocal synergistic effect when mixed with at least one adjuvant selected from a healing agent , an antibiotic agent and/or combinations thereof.2centella asiaticaHydrocotyle asiaticacentella asiatica. A pharmaceutical composition based on (L.) for the treatment of lower limb ulcers according to claim 1 , wherein the composition comprises from about 10% to 18% of ; from about 67% to 75% of sodium acexamate; and from about 10% to 18% of an antibiotic agent.3centella asiaticaHydrocotyle asiatica. A pharmaceutical composition based on (L.) for the treatment of lower limb ulcers according to claim 2 , wherein the composition includes about 60 U of a healing agent.4centella asiaticaHydrocotyle asiatica. A pharmaceutical composition based on (L.) for the treatment of lower limb ulcers according to claim 2 , wherein the antibiotic agent is selected from chloramphenicol claim 2 , sulfathiazole powder claim 2 , ciprofloxacin claim 2 , or any other antibiotic agent required claim 2 , depending on the infection to be treated.5centella asiaticaHydrocotyle asiatica. A pharmaceutical composition based on (L.) for the treatment of lower limb ulcers according to claim 3 , wherein collagenase (clostridiopeptidase A) is used as a healing agent.6centella asiaticaHydrocotyle asiaticacentella asiatica. A pharmaceutical composition based on (L.) for the treatment of lower limb ulcers according to claim 3 , wherein the composition ...

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Номер записи: 26
07-03-2019 дата публикации

DEVICES AND METHODS FOR REDUCING THE APPEARANCE OF CELLULITE

Номер: US20190070215A1
Автор: Avelar Rui, Dominguez Zachary, Kayda Edwin, Perry Tracy Ann, Schwab Justin
Принадлежит:

Methods and devices for use in reducing the appearance of dimpled skin or other undesirable appearance of skin in a cellulitic region of a patient are provided. The methods include the steps of disrupting fibrous septae located beneath the skin of a cellulitic region and introducing a composition beneath the skin, the composition being effective to reduce or prevent regrowth of the fibrous septae. 1. A method for reducing the appearance of dimpled skin or other undesirable appearance of skin in a cellulitic region of a patient , the method comprising the steps of:disrupting fibrous septae located beneath the skin of the cellulitic region; andintroducing a composition beneath the skin of the cellulitic region, the presence of the introduced composition being effective to reduce or prevent regrowth of the disrupted fibrous septae.2. The method of claim 1 , wherein the step of disrupting comprises introducing an enzyme effective to digest the septae.3. The method of claim 1 , wherein the composition comprises a hyaluronic acid gel.4. The method of claim 3 , wherein the composition further comprises an active agent.5. The method of claim 1 , wherein the active agent is an enzyme.6. The method of claim 1 , wherein the step of disrupting comprising introducing a cannula beneath skin of the cellulitic region.7. The method of claim 6 , wherein the cannula has blade effective to sever the septae.8. The method of claim 6 , wherein the cannula comprises a disrupting element comprising a tube having an aperture set apart from a distal tip of the tube claim 6 , the aperture including a sharp beveled edge.9. A device for reducing the appearance of cellulite in a patient claim 6 , the device comprising:a handpiece; and a disrupting element configured and effective to cause disruption of fibrous septae in the cellulitic region; and', 'a cannula for introducing a composition into the cellulitic region to create separation between tissue planes and reduce or prevent regrowth of the ...

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Номер записи: 27
07-03-2019 дата публикации

COMPOSITIONS AND METHODS FOR PRODUCING CLOSTRIDIAL COLLAGENASES

Номер: US20190071659A1
Автор: Wegman Thomas L., Yu Bo
Принадлежит: BioSpecifics Technologies Corp.

The present invention provides a method for producing a drug product comprising a combination of highly purified collagenase I and collagenase II from . The method utilizes an improved medium for the cultivation of which includes a non-meat-derived (i.e., non-mammalian) peptone or vegetable peptone. The method includes one or more of: (1) reducing glucose content in the meat-free or vegetable-derived media; and (2) increasing the salt concentration in the meat-free or vegetable-derived media. Also provided is a drug product which includes collagenase I and collagenase II at an optimized fixed mass ratio, and which has a purity of greater than at least 95%. 1Clostridium histolyticum. A medium for the fermentation of comprising:a. a peptone selected from the group consisting of Oxoid VG100 Vegetable Peptone made from pea, Oxoid VG200 Vegetable Peptone phosphate broth, BBL Phytone Peptone, and BD Difco Select Phytone;b. yeast extract; andc. less than about 5 g/L glucose;wherein the pH of said medium is 7.5-7.9.2. The medium of claim 1 , containing greater than about 5 g/L salt.3. The medium of claim 2 , containing greater than about 7.5 g/L salt.4. The medium of claim 2 , wherein the salt is one or more of potassium phosphate claim 2 , dipotassium phosphate claim 2 , sodium phosphate claim 2 , disodium phosphate claim 2 , sodium chloride claim 2 , potassium chloride claim 2 , calcium chloride claim 2 , or magnesium sulfate.5. The medium of claim 1 , further comprising one or more vitamins selected from the group consisting of ferrous sulfate claim 1 , riboflavin claim 1 , niacin claim 1 , calcium pantothenate claim 1 , pimelic acid claim 1 , pyridoxine hydrochloride and thiamine hydrochloride.6Clostridium histolyticum. A medium for the fermentation of comprising:a. a peptone selected from the group consisting of Oxoid VG100 Vegetable Peptone made from pea, Oxoid VG200 Vegetable Peptone phosphate broth, BBL Phytone Peptone, and BD Difco Select Phytone;b. yeast extract; ...

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Номер записи: 28
12-03-2020 дата публикации

Treatment Method and Product for Uterine Fibroids using Purified Collagenase

Номер: US20200078310A1
Автор: Leppert Phyllis Carolyn, Wegman Thomas L.
Принадлежит:

The invention relates to compositions and methods for treating uterine fibroids, wherein a uterine fibroid treatment agent comprising collagenase in an amount effective to cause shrinkage of uterine fibroids is injected or inserted into the uterine fibroid. 1Clostridium histolyticum. A method for the treatment of uterine fibroids in a patient comprising administering to the uterine fibroid a composition comprising about 0.06 to about 1 mg of collagenase per 1 cm3 uterine fibroid tissue.2. The method of claim 1 , wherein said composition is delivered through a delivery channel into said fibroid claim 1 , wherein the delivery channel is in a needle claim 1 , syringe claim 1 , cannula claim 1 , catheter or jet injector.3. The method of claim 1 , wherein the collagenase is a mixture of collagenase I and collagenase II.4. The method of claim 1 , wherein about 0.1 mg to about 0.8 mg collagenase is administered per cm3 of tissue to be treated.5. The method of claim 1 , wherein about 0.2 mg to about 0.6 mg collagenase is administered per cm3 of tissue to be treated.6. The method of claim 1 , wherein said composition is injected or inserted into said fibroid under image guidance claim 1 , wherein said image is a scope image claim 1 , an MRI image claim 1 , an ultrasound image claim 1 , or a fluoroscopic image.7. The method of claim 1 , wherein said composition further comprises a chemical ablation agent claim 1 , a non-steroidal anti-inflammatory drug claim 1 , an oral contraceptive claim 1 , a GnRH agonist claim 1 , an antiprogestogen claim 1 , or a selective progesterone receptor modulator.8. The method of claim 1 , wherein said composition is a solid dosage form having a largest dimension between 1 mm and 20 mm.9. The method of claim 1 , wherein the composition further comprises a viscosity adjusting agent is present in an amount effective to provide a viscosity ranging from 10 claim 1 ,000 centipoise to 50 claim 1 ,000 centipoise.10. The method of claim 1 , wherein the ...

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Номер записи: 29
25-03-2021 дата публикации

Methods for evaluating tumor cell spheroids using 3d microfluidic cell culture device

Номер: US20210087635A1
Автор: Amir AREF, Cloud P. Paweletz, David BARBIE, Elena Ivanova, Russell W. Jenkins
Принадлежит: Dana Farber Cancer Institute Inc

Provided herein are methods for evaluating tumor cell spheroids in a three-dimensional microfluidic device by determining changes in the relative levels of live cells and dead cells in aliquots cultured under different conditions. Methods described herein allow ex vivo recapitulation of the tumor microenvironment such that the in vivo effectiveness of a test compound in treating tumor tissue may be predicted.

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Номер записи: 30
21-03-2019 дата публикации

METHODS FOR TREATING NETOSIS AND NEUTROPHIL ACTIVATION

Номер: US20190083595A1
Автор: Herrera Victoria L.M., Ruiz-Opazo Nelson
Принадлежит: TRUSTEES OF BOSTON UNIVERSITY

Described herein are methods and compositions relating to methods of inhibiting neutrophils, e.g., inhibiting NET release or NETosis, by means of a DEspR inhibitor, e.g., an anti-DEspR antibody reagent. In some embodiments, the methods can relate to the treatment of a disease, e.g., cancer or a disease wherein neutrophils; NETs; or NETosing or NETting neutrophils contribute to pathogenesis, chronicity, or worsening of disease. In some embodiments, the DEspR inhibitor can be a bi-specific reagent or an antibody-drug conjugate. 1. A method of decreasing the survival or activity of a neutrophil , the method comprising contacting the neutrophil with a DEspR inhibitor.2. A method of preventing or decreasing neutrophil extracellular trap (NET) release , or actPMN NETosis , or vital NETosis in a subject in need thereof , the method comprising administering a therapeutically effective amount of a DEspR inhibitor to the subject.3. The method of claim 1 , wherein the neutrophil is an activated neutrophil (actPMN) or a CD11b+ neutrophil.4. The method of claim 1 , wherein the neutrophil is DEspR.5. The method of claim 2 , wherein the DEspR inhibitor is an anti-DEspR antibody reagent or an antigen-binding fragment thereof.6. The method of claim 5 , wherein the anti-DEspR antibody reagent or antigen-binding fragment thereof is conjugated to an anti-neutrophil or anti-NET reagent.7. The method of claim 5 , wherein the anti-DEspR antibody reagent is an anti-DEspR antibody reagent claim 5 , a monoclonal antibody.8. The method of claim 7 , wherein the anti-DEspR antibody reagent is a bi-specific antibody reagent that can bind specifically to and inhibit i) DEspR and ii) a target that modulates immune cell activity and/or survival selected from:a. a cell surface receptor;b. a ligand or extracellular protein;c. an intracellular protein.9. The method of claim 8 , wherein the cell surface receptor is PD1; CTLA-4; TLR-2; TLR-4; CD14; or CD16810. The method of claim 8 , wherein the ligand ...

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Номер записи: 31
30-03-2017 дата публикации

COMPOSITIONS AND METHODS FOR TREATING COLLAGEN-MEDIATED DISEASES

Номер: US20170087229A1
Автор: Bassett Phillip J., Del Tito, Hitchcock Antony G., JR. Benjamin J., Sabatino Gregory L., Tharia Hazel A., Wegman Thomas L., Yu Bo
Принадлежит:

A drug product comprising a combination of highly purified collagenase I and collagenase II from is disclosed. The drug product includes collagenase I and collagenase II in a ratio of about 1 to 1, with a purity of greater than at least 95%. The invention further disclosed improved fermentation and purification processes for preparing the said drug product. 1Clostridium histolyticum. A drug product comprising isolated and purified collagenase I and collagenase II having the sequence of collagenase I and collagenase II , respectively , wherein the collagenase I and collagenase II have a mass ratio of about 1 to 1 and the drug product is at least 95% by area pure as determined by reverse phase high performance liquid chromatography.2. The drug product of claim 1 , wherein the drug product contains less than about 2% by area aggregated protein as determined by reverse phase high performance liquid chromatography.3. The drug product of claim 1 , wherein the drug product contains less than about 1% by area of clostripain as determined by reverse phase high performance liquid chromatography.4. The drug product of claim 1 , wherein the drug product contains less than about 1% by area of gelatinase as determined by anion exchange chromatography.5. The drug product of claim 1 , wherein the drug product contains less than about 1 ug/mg (w/w) of leupeptin.6. The drug product of claim 1 , wherein the drug product has a bioburden less than 1 cfu/ml claim 1 , and wherein the drug product is sterile.7. The drug product of claim 6 , wherein the drug product contains less than 10 EU/ml of endotoxin.8. The drug product of claim 6 , wherein the drug product contains less than 5 EU/mg of endotoxin.9Clostridium histolyticum. A drug product comprising isolated and purified collagenase I and collagenase II having the sequence of collagenase I and collagenase II claim 6 , respectively claim 6 , wherein the collagenase I and collagenase II have a mass ratio of about 1 to 1 and the drug ...

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Номер записи: 32
02-04-2015 дата публикации

GELATINASE INHIBITORS AND PRODRUGS

Номер: US20150093372A1
Автор: Chang Mayland, Lee Mijoon, Mobashery Shahriar
Принадлежит: University of Notre Dame du Lac

The invention provides compounds, compositions, and methods for the treatment of diseases, disorders, or conditions that are modulated by matrix metalloproteinases (MMPs). The disease, disorder, or condition can include, for example, stroke, neurological disorders, or ophthalmological disorders. The treatment can include administering a compound or composition described herein, thereby providing a prodrug compound that metabolizes to an active MMP inhibitor in vivo. The MMP inhibition can be selective inhibition, for example, selective inhibition of MMP-2, MMP-9, and/or MMP-14. Thus, the invention provides non-mutagenic prodrug compounds of the formulas described herein that result in the inhibition of MMPs upon in vivo administration. 2. The method of wherein each (C-C)alkyl is independently —(CH)— claim 1 , —(CH)— claim 1 , —(CH)— claim 1 , —(CH)— claim 1 , or —(CH)—.3. The method of wherein R—X— is meta or para with respect to the oxygen of the phenoxy moiety to which it is attached.4. The method of wherein the compound of Formula A is a gelatinase inhibitor that has a water solubility that is at least 5000-fold greater than SB-3CT.5. The method of wherein the compound of Formula A inhibits MMP-2 and has a Kof less than 3 μM.6. The method of wherein the compound of Formula A inhibits MMP-9 and has a Kof less than 20 μM.7. The method of wherein the matrix metalloproteinase (MMP) is a gelatinase claim 1 , a collagenase claim 1 , a stromelysin claim 1 , MMP-19 claim 1 , MMP-23 claim 1 , or matrilysin claim 1 , and the activity of the matrix metalloproteinase is inhibited.8. The method of wherein the disease or condition comprises cancer claim 7 , stroke claim 7 , a chronic wound claim 7 , an ophthalmological disorder claim 7 , traumatic brain injury claim 7 , spinal cord injury claim 7 , subarachnoid hemorrhage claim 7 , tuberculosis claim 7 , asthma claim 7 , glaucoma claim 7 , retinal ischemia claim 7 , ischemic optic neuropathy claim 7 , macular degeneration ...

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Номер записи: 33
05-05-2022 дата публикации

CHROMATOGRAPHIC PURIFICATION OF AT LEAST ONE ENZYME SELECTED FROM A GROUP INCLUDING COLLAGENASE TYPE I, COLLAGENASE TYPE II, NEUTRAL PROTEASE AND CLOSTRIPAIN

Номер: US20220135617A1
Автор: DÖDING STEFAN, LAMBRECHT JÖRG, Schrader Thomas
Принадлежит: NORDMARK PHARMA GMBH

The present invention relates to a method for purifying at least one enzyme selected from the group consisting of collagenase type I, collagenase type II, neutral protease and clostripain from a mixture of substances, comprising as a method step at least one hydrophobic interaction chromatography, characterized in that, in the hydrophobic interaction chromatography, the stationary phase comprises a material selected from the group consisting of polypropylene glycol and butyl sepharose. The present invention further relates to the use of an enzyme thus purified for pharmaceutical, cosmetic and/or biochemical purposes.

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Номер записи: 34
06-04-2017 дата публикации

Reduction of Lipoma Tissue

Номер: US20170095542A1
Автор: BRONSTHER BURTON, JACOB ERWIN T., WEGMAN EDWIN H.
Принадлежит:

The amount of adipose tissue, including lipomas, at selected locations in the body is reduced by introducing collagenase or collagenase plus another proteinase into the tissue. 112-. (canceled)13. A method for treating lipoma in a subject in need thereof , comprising administering an effective amount of a pharmaceutical composition comprising collagenase.14. The method of wherein the treatment results in a reduction of lipoma tissue volume of about 25% to about 75% after a single administration of the composition.15. The method of wherein the treatment results in a reduction of lipoma tissue volume of about 100% after a single administration of the composition.16. The method of wherein the lipoma is found at a location selected from the group consisting of the surface of the skin claim 13 , within the skin claim 13 , subcutaneous claim 13 , or anywhere else in the subject.17. The method of wherein the lipoma is a liposarcoma.18. The method of wherein the composition is administered into the lipoma is an amount of about 500 or more ABC units of collagenase per gram of treated tissue.19. The method of wherein the composition is administered into the lipoma is an amount of about 3500 or more ABC units of collagenase per gram of treated tissue.20. The method of wherein the collagenase is purified by chromatographic techniques.21. The method of wherein the collagenase is lyophilized and supplied in vials containing about 2 claim 13 ,200 ABC units of collagenase and a sterile diluent.22. A method of treating lipoma in a subject in need thereof claim 13 , comprising the steps of:a. providing a vial of lyophilized collagenase comprising about 2,200 ABC units of collagenase;b. reconstituting the lyophilized collagenase with a diluent comprising about 0.9% sodium chloride and about 2 mM calcium chloride so as to provide a concentration of about 2,000 ABC units per mL; andc. injecting an effective amount of the reconstituted collagenase into the lipoma.23. The method of ...

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Номер записи: 35
14-04-2016 дата публикации

COMPOSITIONS AND KITS FOR ENZYMATIC DEBRIDEMENT AND METHODS OF USING THE SAME

Номер: US20160101165A1
Автор: LEUNG Kelly Xiaoyu Chen, REILLY Katelyn Elizabeth, Salamone Ann Beal, SALAMONE Joseph Charles
Принадлежит:

A debridement enzyme for necrotic tissue is described that is not dependent upon proteolytic enzymatic activity but instead utilizes the amylase family of enzymes. The amylases (α-, β-, γ-amylase) are noted for the cleavage of the α-glycosidic bonds of polysaccharides, yielding lower molecular weight carbohydrate/sugar fragments. It has now been found that α-amylase is effective in the debridement of devitalized tissue. 1. A debridement composition comprising:0.001 to 99.5 wt % of an amylase component, andat least one pharmaceutically or cosmetically acceptable carrier or excipient in an amount of up to 99.9 wt-%, wherein the percentages are based on a total weight of the debridement composition,wherein, if a proteolytic enzyme component is present, a ratio of the amylase component to the proteolytic enzyme component is at least 4:1.2. The composition according to claim 1 , wherein the amylase component comprises an amylase selected from a group consisting of humans claim 1 , animals claim 1 , bacteria claim 1 , plants claim 1 , fungi and recombinant amylase.3. The composition according to claim 1 , wherein said amylase component comprises at least 80% by weight of α-amylase.4. The composition according to claim 3 , wherein said amylase component comprises up to 20% by weight of an amylase selected from a group consisting of β-amylase claim 3 , γ-amylase claim 3 , and combinations thereof.5. (canceled)6. The composition according to claim 1 , further comprising up to 20% by weight of other hydrolytic enzymes selected from a group consisting of proteases claim 1 , chondroitinases claim 1 , hyaluronidases claim 1 , lipases claim 1 , glycosidases claim 1 , heparanases claim 1 , dermatanases claim 1 , pullulanases claim 1 , N-acetylglucosaminidase claim 1 , lactases claim 1 , phospholipases claim 1 , transglycosylases claim 1 , esterases claim 1 , thioester hydrolyases claim 1 , sulfatases claim 1 , escharases claim 1 , nucleases claim 1 , phosphatases claim 1 , ...

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Номер записи: 36
08-04-2021 дата публикации

TREATMENT OF FIBROSIS WITH GENETICALLY-ENGINEERED MACROPHAGES

Номер: US20210100837A1
Автор: BECKER Lev, Du Jianfeng, GOU Xuewen, Wu Xiaoyang, YUE Jiping, Zhao Yingming
Принадлежит:

Provided herein are macrophages engineered for treating fibrosis and ameliorating the effects of fibrotic lesions in various organs and tissues. Certain embodiments are directed to genetically-engineered macrophages capable of treating fibrosis or reducing fibrotic lesions. In certain aspects macrophages can be genetically-engineered to (1) target extracelluar matrix (ECM) or components thereof, (2) enhance degradation of ECM, or (3) target ECM and enhance degradation of ECM. Further provided is a cellular therapy product comprising a genetically-engineered macrophage comprising at least one of a recombinant targeting protein and a recombinant catalytic enzyme. Further provided is a method of treating an individual for fibrosis comprising administering the cellular therapy product. 1. A genetically-engineered macrophage , comprising:a recombinant extracellular matrix (ECM) targeting protein; and/ora recombinant protease.2. The genetically-engineered macrophage of claim 1 , wherein the recombinant targeting protein is a collagen receptor or a subunit thereof.3. The genetically-engineered macrophage of claim 2 , wherein the collagen receptor or a subunit thereof comprises one or more of an integrin claim 2 , a discoidin domain receptor claim 2 , a mannose family receptor claim 2 , and an immunoglobulin-like receptor.4. The genetically-engineered macrophage of claim 3 , wherein the integrin is an α1β1 claim 3 , α2β1 claim 3 , α10β1 claim 3 , and/or α11β1 integrin.5. The genetically-engineered macrophage of claim 3 , wherein the discoidin domain receptor is DDR1 and/or DDR2.6. The genetically-engineered macrophage of claim 3 , wherein the mannose family receptor is M-phospholipase A2 receptor and/or Endo180.7. The genetically-engineered macrophage of claim 3 , wherein the immunoglobulin-like receptor is glycoprotein VI.8. The genetically-engineered macrophage of claim 1 , wherein the recombinant targeting protein is ITGA-1.9. The genetically-engineered macrophage of ...

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Номер записи: 37
13-04-2017 дата публикации

FUSION PROTEINS OF COLLAGEN-BINDING DOMAIN AND PARATHYROID HORMONE

Номер: US20170101457A1
Автор: Gensure Robert C., Matsushita Osamu, Ponnapakkam Tulasi, Sakon Joshua
Принадлежит:

Fusion proteins containing active agonist or antagonist fragments of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) coupled to a collagen-binding domain are presented. The fusion proteins can be used to promote bone growth, to promote hair growth, to prevent cancer metastasis to bone, to promote immune reconstitution with a bone marrow stem cell transplant, to promote mobilization of bone marrow stem cells for collection for autologous stem cell transplant, and to treat renal osteodystrophy. Pharmaceutical agents comprising a collagen-binding polypeptide segment linked to a non-peptidyl PTH/PTHrP receptor agonist or antagonist are also presented. 160-. (canceled)61. A composition comprising:a collagen-binding polypeptide segment covalently linked to a PTH/PTHrP receptor agonist;wherein the collagen-binding polypeptide segment is a bacterial collagen binding polypeptide segment, wherein the PTH/PTHrP receptor agonist comprises residues 1-14 of SEQ ID NO: 1, and wherein the collagen-binding polypeptide segment comprises a polypeptide selected from the group consisting of residues 38-158 of SEQ ID NO: 1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, polypeptides at least 90% identical to residues 38-158 of SEQ ID NO:1, polypeptides at least 90% identical to SEQ ID NOs 13-17 and fragments consisting of at least 10 consecutive amino acids of any one of SEQ ID NOs: 13-17.62. The composition of claim 61 , wherein the collagen-binding polypeptide segment and the PTH/PTHrP receptor agonist are chemically cross-linked to each other or are polypeptide portions of a fusion protein.63. The composition of claim 61 , wherein the composition has at least 50% greater activity than PTH(1-34) as measured by increased bone mineral density after eight weeks of weekly administration of the composition to a subject in need thereof at equal molar doses of the PTH.64. The composition of claim 61 , wherein the PTH/PTHrP receptor agonist ...

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Номер записи: 38
21-04-2016 дата публикации

Contact lens use in the treatment of an ophthalmologic condition

Номер: US20160109725A1
Автор: Alberto Osio Hernandez-Pons, John Michael Rinehart, Stuart C. Grant
Принадлежит: Osio Corp

The present disclosure relates to the use of contact lenses for treating one or more ophthalmologic conditions. In some embodiments, the contact lenses may be used to treat presbyopia, induced myopia, computer vision syndrome (CVS), insufficient accommodation, or a condition associated with insufficient accommodation. The contact lens may include a number of regions having different geometries (e.g., curvature, width, diameter) depending on the flattest keratonomy of the cornea to achieve a suitable fit. For example, the contact lens may include an optic zone surrounded by an inner peripheral region and an outer peripheral region surrounding the inner peripheral region, each exhibiting varying degrees of curvature. The fitted contact lens may be selected based on a measured sagittal depth and/or eccentricity of the cornea. When fitted, an appropriate amount of fluid may accumulate between the cornea of the eye and the contact lens. In addition, the lens may exhibit a sufficient amount of apical clearance such that when the wearer blinks, the lens moves no more than 1 mm on the eye. Further, the lens and the eye may be mutually structured such that bubbles greater than 0.5 mm in diameter are prevented from forming between the contact lens and the eye. The contact lens may be used in combination with a suitable bioactive agent providing for enhanced visual correction.

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Номер записи: 39
29-04-2021 дата публикации

METHODS FOR TREATING NETOSIS AND NEUTROPHIL ACTIVATION

Номер: US20210121549A1
Автор: Herrera Victoria L.M., Ruiz-Opazo Nelson
Принадлежит: TRUSTEES OF BOSTON UNIVERSITY

Described herein are methods and compositions relating to methods of inhibiting neutrophils, e.g., inhibiting NET release or NETosis, by means of a DEspR inhibitor, e.g., an anti-DEspR antibody reagent. In some embodiments, the methods can relate to the treatment of a disease, e.g., cancer or a disease wherein neutrophils; NETs; or NETosing or NETting neutrophils contribute to pathogenesis, chronicity, or worsening of disease. In some embodiments, the DEspR inhibitor can be a bi-specific reagent or an antibody-drug conjugate. 130.-. (canceled)31. A method of preventing or decreasing neutrophil extracellular trap (NET) levels or release in a subject determined to have increased levels of NETs as indicated by the presence of DEspR+ neutrophils , as compared to a healthy subject , the method comprising administering a therapeutically effective amount of an anti-DEspR antibody reagent to the subject determined to have DEspR+ neutrophils;wherein the therapeutically effective amount of an anti-DEspR antibody reagent does not bind to or cause neutropenia of quiescent neutrophils or CD11b+ neutrophils that do not express DEspR.32. The method of claim 31 , wherein the subject has a condition or disease wherein NETs claim 31 , or NETosing neutrophils claim 31 , or NETting neutrophils contribute to pathogenesis claim 31 , chronicity claim 31 , or worsening of disease.33. The method of claim 32 , wherein the condition or disease is selected from the group consisting of:systemic inflammatory response syndrome (SIRS); acute lung injury (ALI); acute respiratory distress syndrome (ARDS); multi-organ failure or multi-organ dysfunction syndrome (MODS); multi-organ failure or multi-organ dysfunction syndrome (MODS) from ARDS, hemorrhagic shock, surgery, burns, or sepsis; sepsis; sepsis-induced coagulopathy; trauma; multiple sclerosis; acute kidney injury (AKI); AKI-associated tubular necrosis and distant organ injury; post-trauma surgery; hemorrhagic shock; infections; cytokine storms ...

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Номер записи: 40
18-04-2019 дата публикации

Methods for evaluating tumor cell spheroids using 3d microfluidic cell culture device

Номер: US20190112666A1
Автор: Aref Amir, Barbie David, Ivanova Elena, Jenkins Russell W., Paweletz Cloud P.
Принадлежит: Dana-Farber Cancer Institute, Inc.

Provided herein are methods for evaluating tumor cell spheroids in a three-dimensional microfluidic device by determining changes in the relative levels of live cells and dead cells in aliquots cultured under different conditions. Methods described herein allow ex vivo recapitulation of the tumor microenvironment such that the in vivo effectiveness of a test compound in treating tumor tissue may be predicted. 1. A method for evaluating tumor cell spheroids in a three-dimensional microfluidic device , the method comprising:obtaining tumor spheroids from an enzyme treated tumor sample,suspending a first aliquot of the tumor spheroids in biocompatible gel;suspending a second aliquot of the tumor spheroids in biocompatible gel;placing the first aliquot of the tumor spheroids in biocompatible gel in a first three-dimensional device,contacting the first aliquot with a first fluorophore dye selective for dead cells, the first fluorophore dye emitting fluorescence at a first wavelength when bound to a dead cell,contacting the first aliquot with a second fluorophore dye selective for live cells, the second fluorophore dye emitting fluorescence at a second wavelength different from the first wavelength when bound to a live cell,measuring total fluorescence emitted by each of the first and second fluorophore dyes in the first aliquot,culturing the second aliquot in a second three-dimensional device,contacting the second aliquot with the first fluorophore dye,contacting the second aliquot with the second fluorophore dye, wherein the contacting of the second aliquot with the first fluorophore dye and second fluorophore dye is carried out at least 24 hours after the contacting of the first aliquot with the first fluorophore dye and second fluorophore dye,measuring total fluorescence emitted by each of the first and second fluorophore dyes in the second aliquot,wherein an increase or decrease in the ratio of live cells to dead cells in each of the aliquots may be assessed.252-. ( ...

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Номер записи: 41
03-05-2018 дата публикации

ENZYME COMPOSITION FOR THERAPEUTIC MANAGEMENT OF MUSCLE SORENESS

Номер: US20180117127A1
Автор: Majeed Muhammed, Majeed Shaheen, Nagabhushanam Kalyanam
Принадлежит:

The present invention discloses a combination of digestive enzymes (Protease, Amylase, Lactase, Lipase, Cellulase)—DigeZyme® for the therapeutic management of delayed onset muscle soreness (DOMS) 1. A method for therapeutic management of delayed onset muscle soreness using a comprehensive digestive enzyme blend comprising Protease , Amylase , Lactase , Lipase and Cellulase (DigeZyme®) , said method comprising steps of administering effective concentrations of the enzyme blend to mammals presenting with symptoms of delayed onset muscle soreness.2. The method as in claim 1 , wherein the individual enzymes in the digestive blend are present in the concentrations:a) amylase: 24000 DU/g, b) Cellulase: 1100 CU/g, c) Lipase: 200 FIP/g, d) Lactase: 4000 ALU/g and e) Protease: 6000 PC/g.3. The method as in claim 1 , wherein the symptoms of delayed onset muscle soreness include pain claim 1 , tenderness claim 1 , inflammation claim 1 , muscle damage and flexibility.4. The method as in claim 1 , wherein the mammal is human.5. A composition comprising a comprehensive digestive enzyme blend of Protease claim 1 , Amylase claim 1 , Lactase claim 1 , Lipase and Cellulase (DigeZyme®) for use in therapeutic management of Delayed Onset Muscle Soreness (DOMS).6. The composition as in claim 2 , wherein the individual enzymes in the digestive blend are present in the concentrations:a) amylase: 24000 DU/g, b) Cellulase: 1100 CU/g, c) Lipase: 200 FIP/g, d) Lactase: 4000 ALU/g and e) Protease: 6000 PC/g. The invention in general relates to enzymes. More specifically the invention relates to use of the digestive enzymes for the alleviating the symptoms of delayed on set muscle soreness (DOMS).Delayed on set muscle soreness (DOMS) is an exercise induced phenomenon and is a recurrent form of sports injury. It is presented as a sensation of discomfort, predominantly with the skeletal muscles following unaccustomed physical activity. Associated symptoms include muscle shortening, increased ...

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Номер записи: 42
25-04-2019 дата публикации

COMPOSITIONS, SYSTEMS, AND METHODS FOR SCAR TISSUE MODIFICATION

Номер: US20190117746A1
Автор: Gibson Daniel J., SCHULTZ GREGORY SCOTT, SHERWOOD MARK B.
Принадлежит:

Described herein are formulations that can include one or more enzymes that can break down one or more components of scar tissue. Also provided herein are methods of treating scar tissue by administering a formulation provided herein to a subject in need thereof. 1. A formulation for treating excessive bleb formation in a subject , the formulation comprising:an enzyme in an amount effective to form pores in a bleb, where the bleb is formed as the result of a surgical procedure to treat glaucoma in the subject.2. The formulation of claim 1 , wherein the surgical procedure is implantation of an ocular drainage device.3. The formulation of claim 1 , wherein the surgical procedure is a trabeculectomy.4. The formulation of claim 1 , wherein the enzyme is coupled to a magnetic nanoparticle.5. The formulation of claim 1 , wherein the enzyme is selected from the group consisting of: collagenase claim 1 , hyaluronidase claim 1 , serrapeptase claim 1 , nattokinase claim 1 , FAS-ligand and combinations thereof.61. The formulation of claim 1 , wherein the formulation is formulated for ocular injection.7. A formulation for treating scar tissue in a subject claim 1 , the formulation comprising:an agent in an amount effective to form pores in the scar tissue or reduce an amount of scar tissue.8. The formulation of claim 7 , wherein the agent is an enzyme.9. The formulation of claim 1 , wherein the agent is selected from the group consisting of: collagenase claim 1 , hyaluronidase claim 1 , serrapeptase claim 1 , nattokinase claim 1 , FAS-ligand claim 1 , and combinations thereof.10. The formulation of claim 1 , wherein the agent is coupled to a magnetic nanoparticle.11. A method of treating a scar tissue in a subject claim 1 , the method comprising:delivering an agent or formulation thereof to the scar tissue or a region proximate to the scar tissue.12. The method of claim 11 , wherein the agent is an enzyme.13. The method of claim 11 , wherein the agent is selected from the group ...

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Номер записи: 43
01-09-2022 дата публикации

Nanomaterials containing constrained lipids and uses thereof

Номер: US20220273566A1
Автор: Cory Dane SAGO, James Everett Dahlman, Zubao GAN
Принадлежит: Georgia Tech Research Corp

Compositions for delivering nucleic acids to cells or tissue microenvironments are provided. In one embodiment, the compositions are lipid nanoparticle compositions formulated to have reduced splenic and hepatic clearance. It has been discovered that the chemical composition of lipid nanoparticles significantly influences the natural trafficking of the lipid nanoparticles. More specifically, it has been discovered that conformationally constrained ionizable lipids can modify the tropism and clearance profile of lipid nanoparticles without the need of a targeting ligand. It has also been discovered that tropism of the disclosed lipid nanoparticles is size-independent.

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Номер записи: 44
17-05-2018 дата публикации

COMPOSITIONS FOR REMODELING EXTRACELLULAR MATRIX AND METHODS OF USE THEREOF

Номер: US20180133293A1
Автор: SAGI Irit, SOLOMONOV Inna, ZEHORAI Eldar
Принадлежит:

The present invention relates to a method for increasing the embryo implantation rate in a mammalian uterus, by administering to the uterus of a mammal an effective amount of an extracellular matrix remodeling enzyme, as well as to a product comprising an extracellular remodeling enzyme. 1. A method ,wherein the method increases the rate of embryo implantation in the uterus of a mammal, the method comprising:a. administering at least one extra cellular matrix (ECM) remodeling enzyme selected from the group consisting of matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-7, MMP-8 MMP-9, MMP-10, MMP-11, MMP-12, MMP-13, MMP-14, MMP-15, MMP-16, MMP-17, MMP-19, MMP-20, MMP-21, MMP-23, MMP-24, MMP-25, MMP-26, MMP-27, and MMP-28, to the mammal's uterus; andb. introducing at least one embryo into the treated uterus and allowing the introduced embryo to implant into the endometrium of the uterus.2. The method of claim 1 , wherein the at least one extra cellular matrix (ECM) remodeling enzyme is administered to the mammal's uterus at an amount sufficient to remodel the ECM of the endometrium of the uterus.3. The method of claim 1 , wherein the at least one extra cellular matrix (ECM) remodeling enzyme is administered to the mammal's uterus for a time sufficient to remodel the ECM of the endometrium of the uterus.4. The method of claim 1 , wherein the ECM remodeling enzyme is selected from the group consisting of MMP-1 and MMP-13.5. The method of claim 1 , wherein the amount sufficient to remodel the ECM of the endometrium of the uterus is from 0.1 to 10000 ng.6. The method of claim 1 , wherein the amount sufficient to remodel the ECM is from 0.5 to 50 μM.7. The method of claim 1 , wherein the time sufficient to remodel the ECM of the endometrium of the uterus is from 10 minutes to 72 hours.8. A method claim 1 , wherein the method increases the rate of embryo implantation in the uterus of a mammal claim 1 , the method comprising:a. administering at least one extra cellular ...

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Номер записи: 45
28-05-2015 дата публикации

ANIMAL PRODUCT-FREE CULTURE MEDIUM FOR BACTERIA OF THE GENUS CLOSTRIDIUM AND A PROCESS FOR PRODUCING SUPERNATANT COMPRISING ONE OR MORE COLLAGENOLYTIC AND GELATINOLYTIC PROTEASES

Номер: US20150147313A1
Автор: ALEGRIA Marcos Castanheira, ASTOLFI FILHO Spartaco, DELALANA Marina Baiochi Riboldi, FARDELONE Lucidio Cristovao, Moreira Roberto Carlos Debom, Pacheco Ogari de Castro, THIEMANN Josef Ernst
Принадлежит:

The present invention refers to a culture medium and a process for producing proteases with collagenolytic and gelatinolytic activity by bacteria of the genus . Particularly, the present invention refers to an animal product-free culture medium for , characterized by comprising non-animal origin peptones, preferably vegetable peptones, yeast extract and the amino acids cysteine and arginine. The present invention also refers to a process for producing liquid culture supernatant comprising one or more proteases with collagenolytic and gelatinolytic activity, and pharmaceutical composition comprising as active ingredient the supernatant or the supernatant optionality purified. 132-. (canceled)33Clostridium. An animal product-free culture medium for bacteria of the genus comprising water , non-animal origin peptone , or its derivatives , yeast extract and the amino acids cysteine and arginine , or pharmaceutically acceptable salts thereof.34. The culture medium according to claim 33 , wherein the non-animal origin peptone is a vegetable peptone selected from the group consisting of soy claim 33 , cotton claim 33 , wheat claim 33 , sunflower claim 33 , rice claim 33 , peanuts claim 33 , fava bean claim 33 , peas claim 33 , potato claim 33 , corn and mixtures thereof.35. The culture medium according to claim 34 , wherein the vegetable peptone is a soy peptone selected from the group consisting of Hy Soy claim 34 , Soytone claim 34 , Amisoy claim 34 , NZ Soy BL4 claim 34 , NZ Soy BL7 claim 34 , Hy Pep 1510 claim 34 , Hy Pep 1511 claim 34 , Hy Pep 5603 claim 34 , Hy Pep 7504 claim 34 , Stedygro Soy SE50M claim 34 , Proyield Soy claim 34 , SE50MAF-UF claim 34 , Soy peptone 312 claim 34 , Hy Pep 4601 and mixtures thereof.36. The culture medium according to claim 33 , wherein the yeast extract is selected from the group consisting of Bacto YE claim 33 , Hy-Pep YE claim 33 , Hy-Yeast 412 claim 33 , Hy-Yeast 413 claim 33 , Hy-Yeast 502 claim 33 , Hy-Yeast 501 claim 33 , Hy- ...

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Номер записи: 46
26-05-2016 дата публикации

GENE THERAPY VECTOR FOR TREATMENT OF STEROID GLAUCOMA

Номер: US20160144055A1
Автор: Borras Teresa, Spiga Maria-Grazia
Принадлежит:

The presently disclosed subject matter provides an inducible vector comprising a therapeutic gene. In some embodiments a method is provided for treating steroid glaucoma. In some embodiments a method is provided for preventing elevated intraocular pressure in a subject receiving steroid treatment. In some embodiments a method is provided for reversing elevated intraocular pressure in a subject receiving steroid treatment. In some embodiments a steroid treatment method is provided. Also provided are pharmaceutical compositions comprising an inducible vector. 125-. (canceled)27. The method of claim 26 , wherein the vector is an adenovirus vector.28. The method of claim 26 , wherein the SRE is a glucocorticoid response element (GRE).29. (canceled)30. The method of claim 26 , wherein the subject is a mammal.31. The method of claim 26 , wherein the steroid treatment comprises the administration of a glucocorticoid to the subject claim 26 , wherein the glucocorticoid is selected from the group consisting of dexamethasone claim 26 , triamcinalone acetonide claim 26 , prednisolone acetate claim 26 , and combinations thereof.32. The method of claim 26 , wherein administering the vector comprises administering the vector to an ocular tissue of the subject.33. An steroid treatment method comprising:i) providing a subject in need of steroid treatment;ii) administering a vector comprising a coding sequence for MMP1, a minimal promoter and a SRE, wherein the coding sequence is under the transcriptional control of the SRE, wherein the coding sequence corresponds to a gene susceptible to altered expression in the presence of a steroid in vivo; andiii) administering a steroid to the subject.34. The method of claim 33 , wherein the subject in need of steroid treatment comprises a subject suffering from inflammation claim 33 , ocular inflammation claim 33 , macular edema claim 33 , choroidal neovascularization claim 33 , or any other eye or systemic condition requiring administration ...

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Номер записи: 47
09-05-2019 дата публикации

FUSION PROTEINS OF COLLAGEN-BINDING DOMAIN AND PARATHYROID HORMONE

Номер: US20190135890A1
Автор: Gensure Robert C., Matsushita Osamu, Ponnapakkam Tulasi, Sakon Joshua
Принадлежит:

Fusion proteins containing active agonist or antagonist fragments of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) coupled to a collagen-binding domain are presented. The fusion proteins can be used to promote bone growth, to promote hair growth, to prevent cancer metastasis to bone, to promote immune reconstitution with a bone marrow stem cell transplant, to promote mobilization of bone marrow stem cells for collection for autologous stem cell transplant, and to treat renal osteodystrophy. Pharmaceutical agents comprising a collagen-binding polypeptide segment linked to a non-peptidyl PTH/PTHrP receptor agonist or antagonist are also presented. 160-. (canceled)61. A composition comprising:a collagen-binding polypeptide segment covalently linked to a PTH/PTHrP receptor antagonist; wherein the collagen-binding polypeptide segment is a bacterial collagen binding polypeptide segment, wherein the PTH/PTHrP receptor antagonist comprises the polypeptide selected from the group consisting of residues 7-14 of SEQ ID NO: 7, residues 7-33 of SEQ ID NO: 7, residues 7-34 of SEQ ID NO: 7, SEQ ID NO: 11 and residues 7-34 of SEQ ID NO: 8, and wherein the collagen-binding polypeptide segment comprises thee polypeptide selected from the group consisting of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, polypeptides at least 90% identical to SEQ ID NOs 13-17 and fragments consisting of at least 10 consecutive amino acids of any one of SEQ ID NOs: 13-17.62. The composition of claim 61 , wherein the collagen-binding polypeptide segment and the PTH/PTHrP receptor antagonist are chemically cross-linked to each other or are polypeptide portions of a fusion protein.63. The composition of claim 61 , wherein the PTH/PTHrP receptor antagonist is a polypeptide and the N-terminus of the collagen-binding polypeptide segment is linked directly or through a linker polypeptide segment to the C-terminus of the PTH/PTHrP receptor antagonist ...

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Номер записи: 48
25-05-2017 дата публикации

Methods of Novel Therapeutic Candidate Identification Through Gene Expression Analysis in Vascular-Related Disease

Номер: US20170145505A1
Автор: Mann David M.
Принадлежит:

Multiple treatment regimens for vascular-related diseases and disorders. Methods of treating vascular-related disorders based on gene expression studies from samples collected from individuals having symptoms of vascular-related disorders. Additionally, methods for diagnostic techniques to focus treatment regimens. Finally, methods of treating vascular-related disorders involving targeting microRNAs. 1. A method of diagnosing a vascular-related disease in an individual comprising the steps of: ["1) obtaining a biopsy sample from the individual's artery during progression of the vascular-related disease;", '2) obtaining an artery sample from a non-diseased control;', '3) extracting RNA from the samples in steps 1) and 2);', '4) obtaining gene products from the RNA extracted in steps 3); and', '5) comparing gene expression levels from the biopsy sample with the non-diseased control; and, 'a) identifying at least one gene that is upregulated or downregulated in the vascular-related disease comprising the steps ofb) associating the genes upregulated in the biopsy sample with an inhibitor of the gene products for administration to the individual and genes downregulated in the biopsy sample with a promoter of the gene products for administration to the individual.2. The method of claim 1 , wherein the vascular-related disease is pulmonary arterial hypertension.3. The method of claim 1 , wherein the biopsy sample is extracted using an endoarterial catheter.4. A method of identifying microRNA dysregulated in an individual having a vascular-related disease comprising the steps of:a) obtaining a biopsy sample from the individual's artery during progression of the vascular-related disease;b) obtaining an artery sample from a non-diseased control;c) extracting RNA from the samples in steps a) and b);d) converting the RNA to cDNA;e) comparing levels of microRNA expression from the biopsy sample with the non-diseased control; andf) identifying the microRNA dysregulated in the ...

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Номер записи: 49
01-06-2017 дата публикации

Compositions and kits for enzymatic debridement and methods of using the same

Номер: US20170151314A1
Автор: Ann Beal Salamone, Joseph Charles SALAMONE, Katelyn Elizabeth REILLY, Kelly Xiaoyu Chen LEUNG
Принадлежит: Rochal Industries LLC

A debridement enzyme for necrotic tissue is described that is not dependent upon proteolytic enzymatic activity but instead utilizes the amylase family of enzymes. The amylases (α-, β-, γ-amylase) are noted for the cleavage of the α-glycosidic bonds of polysaccharides, yielding lower molecular weight carbohydrate/sugar fragments. It has now been found that α-amylase is effective in the debridement of devitalized tissue.

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Номер записи: 50
09-06-2016 дата публикации

METHOD OF TREATING FIBROPROLIFERATIVE DISORDERS INCLUDING DUPUYTREN'S DISEASE WITH ONE OR MORE SPECIFIC HUMAN MATRIX METALLOPROTEINASE AND A TNF ANTAGONIST

Номер: US20160158325A1
Автор: Larsen Glenn
Принадлежит: 180 Therapeutics LP

The subject invention also provides a method of treating a subject afflicted with a fibroproliferative disorder comprising periodically administering to the patient an amount of one or more human matrix metalloproteinase, wherein the one or more human matrix metalloproteinase are selected from human metalloproteinase-1 (MMP-1), human metalloproteinase-2 (MMP-2), human metalloproteinase-3 (MMP-3), human metalloproteinase-7 (MMP-7), human metalloproteinase-8 (MMP-8), human metalloproteinase-9 (MMP-9), human metalloproteinase-10 (MMP-10), human metalloproteinase-11 (MMP-11), metalloproteinase-12 (MMP-12), and human metalloproteinase-13 (MMP-13), and wherein the amount is effective to treat the subject. In an embodiment, the invention further comprises periodically administering to the subject an amount of TNF antagonist, wherein the amount of one or more the human matrix metalloproteinase and the amount of TNF antagonist when taken together are effective to treat the subject. 1. A method of treating a subject afflicted with a fibroproliferative disorder comprising periodically administering to the patient an amount of one or more human matrix metalloproteinase , wherein the one or more human matrix metalloproteinase is or are selected from the group consisting of human metalloproteinase-1 (MMP-1) , human metalloproteinase-2 (MMP-2) , human metalloproteinase-3 (MMP-3) , human metalloproteinase-7 (MMP-7) , human metalloproteinase-8 (MMP-8) , human metalloproteinase-9 (MMP-9) , human metalloproteinase-10 (MMP-10) , human metalloproteinase-11 (MMP-11) , metalloproteinase-12 (MMP-12) , and human metalloproteinase-13 (MMP-13) , and wherein the amount is effective to treat the subject.2. The method of further comprising periodically administering to the subject an amount of a TNF antagonist claim 1 , wherein the amount of said one or more the human matrix metalloproteinase and the amount of said TNF antagonist when taken together are effective to treat the subject.3. The ...

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Номер записи: 51
23-05-2019 дата публикации

DELIVERY SYSTEM COMPRISING A PROTEOLYTIC ENZYME OR EFFECTOR THEREOF FOR USE IN A METHOD FOR ORAL TREATMENT AND USES THEREOF

Номер: US20190151423A1
Автор: HERMAN Avishay, Schroeder Avraham D., ZINGER Assaf Yosef
Принадлежит:

The present disclosure provides a delivery system comprising (i) a physiologically acceptable carrier and (ii) a proteolytic enzyme or effector thereof for use in a method for relaxing fibers within a subject's oral cavity. In some embodiments, the relaxation is for use in tooth manipulation (particularly repositioning). In some embodiments, the method involves the use of the proteolytic enzyme or effector thereof at a concentration effective to cause relaxation of fibers between the tooth's alveolar bone and gingiva while maintaining integrity of the fibers surrounding the tooth. Also disclosed herein are methods for fiber relaxation and/or repositioning of tooth making use of the proteolytic enzyme or effector thereof. 1. A method for reducing fiber tension , fiber volume or both within a fiber of a subject's connective tissue in a subject in need thereof , the method comprising administering to said subject a composition comprising:a. a physiologically acceptable carrier; andb. a lipid formulation encapsulating a proteolytic enzyme or an effector thereof, wherein the proteolytic enzyme or effector thereof is at a concentration effective to cause relaxation of said fibers of a connective tissue;thereby reducing fiber tension, fiber volume or both within said fiber of a subject's connective tissue in a subject in need thereof.2. The method of claim 1 , wherein said reducing fiber tension claim 1 , fiber volume or both comprises causing relaxation in said fiber of said connective tissue.3. The method of claim 1 , wherein said proteolytic enzyme or effector thereof is at a concentration that maintains integrity and does not rupture said fiber of a connective tissue.4. The method of claim 1 , wherein said proteolytic enzyme has absolute specificity to said proteolytic enzyme's target.5. The method of claim 4 , wherein said absolute specificity to a target comprises negligible or no detectable catalytic activity to any other molecule.6. The method of claim 1 , wherein ...

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Номер записи: 52
14-05-2020 дата публикации

RNAS FOR WOUND HEALING

Номер: US20200149026A1
Автор: HORSCROFT Nigel, PÖNISCH Marion, WEINL Christine
Принадлежит:

The present invention relates to an RNA encoding a therapeutic protein, in particular a collagenase, growth factor, cytokine, receptor, chaperone or signal transduction inhibitor. In particular, the present invention relates to RNA suitable for treatment of wounds, specifically for promoting wound healing. The present invention concerns such RNA as well as pharmaceutical compositions and kits and combinations comprising the RNA. Furthermore, the present invention relates to the RNA, pharmaceutical compositions, kits as disclosed herein for use in the treatment of wounds, specifically for promoting wound healing. 1. A method of treating a wound in a subject in need thereof comprising administering to the subject an effective amount of RNA comprising at least one coding sequence , wherein the coding sequence encodes at least one therapeutic protein selected from a collagenase selected from MMP1; ColG; ColH; ColG/ColH mixture; MMP8; MMP9; MMP13; a growth factor selected from HGF; VEGFA; FGF21; AMELX; AMELY; ssAMELX; ssAMELX-001-1; ssAMELX-001-2; ssAMELX-002; ssAMELX-003; ssAMELX-004; ssAMELX-201; BMP1; BMP2; BMP4; BMP6; BMP7; EGF; EREG; FGF1; FGF2; FGF7; HBEGF; IGF1; IGF2; INHBA; INHBB; PDGFA; PDGFB; PDGFC; PDGFD; TGFA; TGFB1; TGFB2; TGFB3; PGF; VEGFB; VEGFC or VEGFD; a cytokine selected from IL6 or CCL7; a receptor selected from ITGAM , CCR1 or TNFRSF1B; a chaperone selected from HSPA1A; HSPA1B; HSPA1L; HSPA2; HSPA4; HSPA4L; HSPA5; HSPA6; HSPA7; HSPA8; HSPA9; HSPA12A; HSPA12B; HSPA13; HSPA14; HSPH1; HSP90AA1; HSP90AA3P; HSP90AB1; HSP90B1; HYOU1 , extracellular matrix protease or TRAP1; or SOCS3.2. The method of claim 1 , wherein said RNA comprises at least one coding sequence claim 1 , wherein the coding sequence encodes a therapeutic protein selected from a collagenase claim 1 , preferably selected from MMP1; ColG or ColH.3. (canceled)4. The method of claim 1 , wherein the therapeutic protein comprises or consists of an amino acid sequence selected from the group ...

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Номер записи: 53
29-09-2022 дата публикации

COLLAGENASE FORMULATIONS AND METHODS OF PRODUCING THE SAME

Номер: US20220305094A1
Автор: Sukuru Karunakar
Принадлежит:

Disclosed herein are improved collagenase-containing formulations and methods of preparing the same. The collagenase-containing formulations comprise a collagenase, about 30 mM to about 240 mM of a disaccharide, about 50 mM to about 800 mM of mannitol, and about 6 mM to about 10 mM of a Tris-HCl. Lyophilized and reconstituted formulations are also provided. 1. A formulation comprising:a collagenase;about 30 mM to about 240 mM of a disaccharide;about 50 mM to about 800 mM of mannitol; andabout 6 mM to about 10 mM of a Tris-HCl.2. The formulation of claim 1 , wherein the collagenase comprises a collagenase I.3. The formulation of claim 2 , wherein the collagenase I comprises the amino acid sequence of SEQ ID NO: 1.4. The formulation of claim 1 , wherein the collagenase comprises a collagenase II.5. The formulation of claim 4 , wherein the collagenase II comprises the amino acid sequence of SEQ ID NO: 2.6. The formulation of claim 1 , wherein the collagenase comprises a mixture of collagenase I and collagenase II.7. The formulation of claim 6 , wherein the collagenase I comprises the amino acid sequence of SEQ ID NO: 1 and the collagenase II comprises the amino acid sequence of SEQ ID NO: 2.8Clostridium histolyticum. The formulation of claim 7 , wherein the collagenase is collagenase (CCH).9. The formulation of claim 1 , wherein the disaccharide comprises sucrose or trehalose.10. The formulation of claim 1 , wherein the pH of the formulation is about 7.8 to about 8.8.11. The formulation of claim 1 , wherein the formulation comprises:CCH;about 60 mM sucrose;about 225 mM mannitol; andabout 10 mM Tris-HCl,wherein the formulation has a pH of about 8.5.12. The formulation of claim 1 , further comprising a surfactant comprising polysorbate 20 claim 1 , polysorbate 80 claim 1 , or poloxamer 188.13. The formulation of claim 12 , comprising from about 0.01% to about 2% of the surfactant.14. The formulation of claim 13 , comprising about 0.02% of the surfactant.15. The ...

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Номер записи: 54
25-06-2015 дата публикации

Methods for Treating Adhesive Capsulitis

Номер: US20150174216A1
Автор: Edward Wang, Marie A. Badalamente
Принадлежит: Research Foundation of State University of New York

The invention relates to the discovery that collagenase injections are effective in lyse the collagenous adhesions in the shoulder and treat the disorder, adhesive capsulitis. As such, the invention relates to methods of treating or preventing adhesive capsulitis, or frozen shoulder, in a patient in need of such treatment comprising injecting or otherwise delivering an effective amount of collagenase to the collagenous adhesions in the shoulder. The invention also relates to the use of collagenase in the manufacture of a medicament to treat adhesive capsulitis.

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Номер записи: 55
05-07-2018 дата публикации

Animal product-free culture medium for bacteria of the genus clostridium and a process for producing supernatant comprising one or more collagenolytic and gelatinolytic proteases

Номер: US20180187144A1
Автор: Josef Ernst Thiemann, Lucidio Cristóvão Fardelone, Marcos Castanheira Alegria, Marina Baiochi Riboldi Delalana, Ogari De Castro Pacheco, Roberto Carlos Debom Moreira, Spartaco Astolfi Filho
Принадлежит: Cristalia Produtos Quimicos e Farmaceuticos Ltda

The present invention refers to a culture medium and a process for producing proteases with collagenolytic and gelatinolytic activity by bacteria of the genus Clostridium . Particularly, the present invention refers to an animal product-free culture medium for C. histolyticum , characterized by comprising non-animal origin peptones, preferably vegetable peptones, yeast extract and the amino acids cysteine and arginine. The present invention also refers to a process for producing Clostridium histolyticum liquid culture supernatant comprising one or more proteases with collagenolytic and gelatinolytic activity, and pharmaceutical composition comprising as active ingredient the supernatant or the supernatant optionality purified.

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Номер записи: 56
11-06-2020 дата публикации

COLLAGEN-MIMETIC PEPTIDE MEDIATED DELIVERY OF NUCLEIC ACID CARRIERS FOR EFFICIENT DELIVERY FROM COLLAGEN

Номер: US20200179490A1
Автор: KIICK Kristi, Sullivan Millicent, Urello Morgan
Принадлежит: University of Delaware

The present invention provides a composition for delivering a polynucleotide into cells via a polyplex. The polyplex comprises the polynucleotide and a polymer. The composition comprises the polyplex, a collagen-mimetic peptide (CMP) and collagen fragments. The CMP is bound to the polyplex and the collagen fragments. Also provided are the uses of the composition in methods of delivering a polynucleotide into cells as well as methods of improving wound healing in a subject, enhancing cell proliferation in a subject, enhancing production of extracellular matrix by cells in a subject and/or enhancing cell migration by cells in a subject. 1. A method of delivering a polyplex into cells , wherein the cells are in a subject , wherein the polyplex comprises at least one polymer and at least one polynucleotide , comprising administering an effective amount of a composition to the cells , wherein the composition comprises(a) at least one collagen-mimetic peptide (CMP),(b) the polyplex, wherein the at least one CMP is bound to the polyplex, and(c) collagen or fragments thereof, wherein the at least one CMP is bound to the collagen or fragments thereof.2. The method of claim 1 , wherein the polynucleotide is DNA.3. The method of claim 1 , wherein the polynucleotide is RNA.4. The method of claim 1 , wherein the at least one CMP is bound to the polyplex via a covalent linkage.5. The method of claim 1 , wherein the at least one CMP is bound to the polyplex via a noncovalent linkage.6. The method of claim 1 , wherein the at least one polynucleotide encodes at least one protein claim 1 , further comprising expressing the at least one protein in the cells.7. The method of claim 1 , wherein the cells express at least one protein claim 1 , wherein the at least one polynucleotide encodes at least one silencing RNA capable of suppressing expression of the at least one protein claim 1 , the method further comprising suppressing the expression of the at least one protein in the cells.8. ...

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Номер записи: 57
22-07-2021 дата публикации

Treatment Method and Product for Uterine Fibroids using Purified Collagenase

Номер: US20210220284A1
Автор: Leppert Phyllis Carolyn, Wegman Thomas L.
Принадлежит:

The invention relates to compositions and methods for treating uterine fibroids, wherein a uterine fibroid treatment agent comprising collagenase in an amount effective to cause shrinkage of uterine fibroids is injected or inserted into the uterine fibroid. 1Clostridium histolyticum. A method for the treatment of uterine fibroids in a patient comprising administering to the uterine fibroid a composition comprising about 0.06 to about 1 mg of collagenase per 1 cm3 uterine fibroid tissue.2. The method of claim 1 , wherein said composition is delivered through a delivery channel into said fibroid claim 1 , wherein the delivery channel is in a needle claim 1 , syringe claim 1 , cannula claim 1 , catheter or jet injector.3. The method of claim 1 , wherein the collagenase is a mixture of collagenase I and collagenase II.4. The method of claim 1 , wherein about 0.1 mg to about 0.8 mg collagenase is administered per cm3 of tissue to be treated.5. The method of claim 1 , wherein about 0.2 mg to about 0.6 mg collagenase is administered per cm3 of tissue to be treated.6. The method of claim 1 , wherein said composition is injected or inserted into said fibroid under image guidance claim 1 , wherein said image is a scope image claim 1 , an MRI image claim 1 , an ultrasound image claim 1 , or a fluoroscopic image.7. The method of claim 1 , wherein said composition further comprises a chemical ablation agent claim 1 , a non-steroidal anti-inflammatory drug claim 1 , an oral contraceptive claim 1 , a GnRH agonist claim 1 , an antiprogestogen claim 1 , or a selective progesterone receptor modulator.8. The method of claim 1 , wherein said composition is a solid dosage form having a largest dimension between 1 mm and 20 mm.9. The method of claim 1 , wherein the composition further comprises a viscosity adjusting agent is present in an amount effective to provide a viscosity ranging from 10 claim 1 ,000 centipoise to 50 claim 1 ,000 centipoise.10. The method of claim 1 , wherein the ...

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Номер записи: 58
20-07-2017 дата публикации

DELIVERY OF THERAPEUTIC AGENTS BY A COLLAGEN BINDING PROTEIN

Номер: US20170204390A1
Автор: Gensure Robert C., Katikaneni Ranjitha, Koide Takaki, Matsushita Osamu, NISHI Nozomu, Philominathan Sagaya Theresa Leena, Ponnapakkam Tulasi, Sakon Joshua
Принадлежит:

Methods of delivering therapeutic agents by administering compositions including a bacterial collagen-binding polypeptide segment linked to the therapeutic agent to subjects in need of treatment with the therapeutic agent are provided. In these methods, the therapeutic agent is not a PTH/PTHrP receptor agonist or antagonist, basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF). The bacterial collagen-binding polypeptide segment delivers the agent to sites of partially untwisted or under-twisted collagen. Methods of treating collagenopathies using a composition including a collagen-binding polypeptide and a PTH/PTHrP receptor agonist are also provided. In addition, methods of treating hyperparathyroidism, and hair loss using compositions comprising a collagen binding polypeptide and a PTH/PTHrP receptor agonist are provided. Finally, methods of reducing hair regrowth by administering a composition including a collagen binding polypeptide and a PTH/PTHrP receptor antagonist are provided. 1Clostridium, BacillusVibrio. A method of delivering a therapeutic agent comprising: administering a composition comprising a bacterial collagen-binding polypeptide segment linked to a therapeutic agent to a subject in need of treatment with the therapeutic agent , wherein the therapeutic agent is not a PTH/PTHrP receptor agonist or antagonist , and wherein the bacterial collagen-binding polypeptide segment delivers the agent to sites of partially untwisted or under-twisted collagen , wherein the therapeutic agent is being delivered to treat a collagenopathy and wherein the bacterial collagen-binding polypeptide segment comprises a collagen-binding polypeptide derived from an M9 peptidase selected from the group consisting of and , one of SEQ ID NOs: 6 , 13-34 or a fragment thereof , residues 34-158 of SEQ ID NO: 1 , a fragment of at least 8 consecutive amino acids from residues 34-158 of SEQ ID NO: 1 , or a peptide that is at least 90% identical to residues 34-158 ...

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Номер записи: 59
27-07-2017 дата публикации

DELIVERY SYSTEM COMPRISING A PROTEOLYTIC ENZYME OR EFFECTOR THEREOF FOR USE IN A METHOD FOR ORAL TREATMENT AND USES THEREOF

Номер: US20170209551A1
Автор: HERMAN Avishay, Schroeder Avraham D., ZINGER Assaf Yosef
Принадлежит:

The present disclosure provides a delivery system comprising (i) a physiologically acceptable carrier and (ii) a proteolytic enzyme or effector thereof for use in a method for relaxing fibers within a subject's oral cavity. In some embodiments, the relaxation is for use in tooth manipulation (particularly repositioning). In some embodiments, the method involves the use of the proteolytic enzyme or effector thereof at a concentration effective to cause relaxation of fibers between the tooth's alveolar bone and gingiva while maintaining integrity of the fibers surrounding the tooth. Also disclosed herein are methods for fiber relaxation and/or repositioning of tooth making use of the proteolytic enzyme or effector thereof. 142.-. (canceled)43. A delivery system for use in a method for relaxing fibers within an oral cavity of a subject comprising (i) a physiologically acceptable carrier and (ii) a proteolytic enzyme or an effector thereof , wherein the proteolytic enzyme or effector thereof is at a concentration effective to cause relaxation of at least fibers between a tooth's alveolar bone and gingival.44. The delivery system of claim 43 , wherein said concentration is effective to cause said relaxation while maintaining integrity of the fibers surrounding said tooth.45. The delivery system of claim 43 , wherein said proteolytic enzyme is directed to Type I collagen.46. The delivery system of claim 44 , wherein said proteolytic enzyme is collagenase.47. The delivery system of claim 43 , wherein the concentration of said proteolytic enzyme or effector thereof is equal to or less than 1 mg/ml.48. The delivery system of claim 47 , wherein the concentration of proteolytic enzyme or effector thereof is equal to or less than 1.0 mg/ml.49. The delivery system of claim 48 , comprising liposomes encapsulating said proteolytic enzyme or effector thereof.50. The delivery system of claim 49 , wherein said liposomes are unilamellar or multi-lamellar liposomes.51. The delivery ...

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Номер записи: 60
27-07-2017 дата публикации

PHARMACEUTICAL COMPOSITIONS CONTAINING HYALURONIC ACID AND COLLAGENASE FOR THE TOPICAL TREATMENT OF WOUNDS, BURNS AND ULCERS

Номер: US20170209552A1
Автор: Callegaro Lanfranco, CARUSO Salvatore, Gennari Giovanni, GIANNELLI Antonio, VACCARO Susanna
Принадлежит: FIDIA FARMACEUTICI S.p.A.

The present invention concerns new compositions containing hyaluronic acid or the derivatives thereof in association with the proteolytic enzyme collagenase (and relative pharmaceutical formulations) for the preparation of a dressing for topical treatment of various kinds of wounds, burns of varying depth, pressure sores, vascular ulcers and diabetic foot ulcers as well as for the treatment of hypertrophic and keloid scars. 1. A method for treating Dupuytren's contracture which comprises administering to a subject having Dupuytren's contracture an injectable form of a pharmaceutical composition comprising hyaluronic acid or at least one hyaluronic acid derivative and the proteolytic enzyme collagenase ,{'i': 'Vibrio', 'wherein said collagenase is from the non-pathogenic micro-organism belonging to the strain Alginolyticus sub. Iophagus,'}{'sup': '6', 'wherein said hyaluronic acid or the hyaluronic acid used in the preparation of its derivative has a molecular weight of between 400 and 3×10Da;'}wherein the hyaluronic acid acts to reduce the rate of the proteolytic activity of the collagenase in the subject.2. The method according to claim 1 , wherein said pharmaceutical composition further comprises an additional pharmacologically and/or biologically active substance.3. The method according to claim 1 , wherein the concentration of the enzyme collagenase ranges between 0.1 and 20 U/milligrams of said hyaluronic acid or of said hyaluronic acid derivative.4. The method according to claim 1 , wherein the concentration of the enzyme collagenase is between 0.2 and 10 U/milligrams of said hyaluronic acid or of said hyaluronic acid derivative.5. The method according to claim 1 , wherein the concentration of said hyaluronic acid or of said hyaluronic acid derivative is between 0.1 and 2% w/w.6. The method according to claim 1 , wherein the concentration of said hyaluronic acid or of said hyaluronic acid derivative is between 0.2 and 0.4% w/w.7. The method according to claim ...

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Номер записи: 61
27-07-2017 дата публикации

AGENTS AND METHODS FOR TREATING AND PREVENTING SEBORRHEIC KERATOSIS

Номер: US20170211041A1
Автор: Lee Sam W., Mandinova Anna I., Neel Victor A.
Принадлежит: The General Hospital Corporation

Provided herein are methods and assays for isolating and culturing seborrheic keratosis cells ex vivo. Also provided herein are screening assays using cultured seborrheic keratosis cells and methods for treating seborrheic keratosis in a subject. 1. A method for culturing seborrheic keratosis cells ex vivo , the method comprising:(a) contacting a biological sample comprising seborrheic keratosis cells obtained from a subject with a solution comprising a dispase enzyme at a temperature and for a time sufficient to initiate dissociation of the seborrheic keratosis cells from the biological sample, and(b) culturing the dissociated seborrheic keratosis cells.2. The method of claim 1 , wherein the temperature is below a standard room temperature of 21° C.3. The method of claim 1 , wherein the time sufficient to initiate digestion of the seborrheic keratosis cells is at least 15 hours.4. The method of claim 1 , further comprising a step of contacting the biological sample comprising seborrheic keratosis cells with an additional protease.5. The method of claim 4 , wherein the additional protease is Trypsin.6. The method of claim 1 , further comprising a step of adding a culture medium and filtering larger particles from the dissociated cells before the culturing of step (b).7. The method of claim 6 , wherein the dissociated cells are cultured on coated plates. This application is a Continuation of U.S. application Ser. No. 15/254,344, filed on Sep. 1, 2016, which is a Divisional of U.S. application Ser. No. 14/395,737 (now U.S. Pat. No. 9,458,462), filed on Oct. 20, 2014, which is a 35 U.S.C. 371 National Stage Application of International Application No. PCT/US2013/038358, filed on Apr. 26, 2013, which designates the United States, and which claims benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 61/638,684, filed on Apr. 26, 2012, the contents of each of which are incorporated herein by reference in their entireties.Human skin is continuously exposed ...

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Номер записи: 62
03-08-2017 дата публикации

Grimontia-hollisae-derived recombinant collagenase and enzyme agent for cell separation

Номер: US20170218352A1
Автор: Katsumasa Iijima, Keisuke Tanaka, Naoko Teramura, Osamu Hayashida, Shoji Takeuchi, Shunji Hattori, Teru Okitsu
Принадлежит: Nippi Inc, University of Tokyo NUC

Recombinant collagenases with a stable specific activity and enzyme agents for cell and tissue dissociation such a recombinant are provided. The recombinant collagenase is derived from Grimontia hollisae -derived collagenase is characterized by having, from the N terminus to the C terminus, a collagenase catalytic domain, a linker region sequence, and a prepeptidase C terminal domain, which Grimontia hollisae -derived recombinant collagenase does not comprise at least the prepeptidase C terminal domain. The obtained recombinant collagenase has a high and stable specific activity.

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Номер записи: 63
02-07-2020 дата публикации

Clostridium Histolyticum Enzymes and Methods for the Use Thereof

Номер: US20200206326A1
Автор: Wayne K. Herber
Принадлежит: Endo Global Ventures

The invention relates to recombinant nucleic acid and polypeptides encoding collagenase I and collagenase II, methods for the preparation thereof and methods for the use thereof. The invention also encompasses methods related to releasing a composition comprising collagenase prior to therapeutic administration.

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Номер записи: 64
30-10-2014 дата публикации

Pharmaceutical Compositions and Methods for Digesting Atherosclerotic Plaques

Номер: US20140322190A1
Автор: Guillermo A. Ameer, Melina R. Kibbe, Vinit N. Varu
Принадлежит: Northwestern University

Disclosed are pharmaceutical compositions and methods for digesting atherosclerotic plaques in a patient in need thereof. The compositions include and the methods utilize a mixture of collagenases for digesting plaques and optionally may include or utilize additional agents such as cyclodextrins, chelating agents, and tissue plasminogen activator.

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Номер записи: 65
17-08-2017 дата публикации

HYALINE CARTILAGE SHAPING

Номер: US20170231651A1
Автор: Dinger Fred, Frazier Andrew
Принадлежит: AERIN MEDICAL, INC.

Disclosed embodiments include devices and methods for shaping, bending, and/or volumetrically reducing rigid cartilaginous structures, such as hyaline cartilage in the septum. In the case of septal cartilage, shaping, bending, or reducing the cartilage would be useful for reducing nasal obstruction or to improve the cosmetic appearance of the nose. 1. A method for modifying a nasal septum of a subject's nose , the method comprising:applying a substance to the nasal septum, wherein the substance is configured to modify cartilage of the nasal septum;inserting an energy delivery device into the subject's nose; andapplying energy to the nasal septum using the energy delivery device to reshape the cartilage of the nasal septum.2. The method of claim 1 , wherein the substance is selected from the group consisting of collagenase claim 1 , hyaluronidase claim 1 , tosyl lysyl chloromethane claim 1 , trypsin claim 1 , and trypsin/EDTA.3. The method of claim 1 , wherein the substance is configured to soften the cartilage of the nasal septum.4. The method of claim 1 , wherein the substance is configured to dissolve proteoglycan structures of the cartilage.5. The method of claim 1 , wherein the substance comprises about 0.5 ml to about 2.5 ml of collagenase at a concentration of about 1 mg/ml to about 10 mg/ml.6. The method of claim 1 , wherein the substance comprises between about 0.5 ml to about 2.5 ml of trypsin at a concentration of about 10 μg/ml to about 100 μg/ml.7. The method of claim 1 , further comprising allowing the substance to reside on the nasal septum for a period of time before applying the energy to the nasal septum.8. The method of claim 7 , wherein the period of time is between about 15 minutes and about 90 minutes.9. The method of claim 7 , wherein the period of time is selected to be sufficient for the substance to create a band of degraded cartilage ranging from about 100 μm to about 1 mm from a surface of the cartilage.10. The method of claim 1 , wherein ...

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Номер записи: 66
23-08-2018 дата публикации

UMBILICAL CORD-DERIVED ADHESIVE STEM CELLS, PREPARATION METHOD THEREFOR, AND USE THEREOF

Номер: US20180236007A1
Автор: KANG Ahreum, KIM Hye Sun, Kim JiHye, Shin Jeong Min, YU Ji Min
Принадлежит: CHA BIOTECH CO., LTD.

Disclosed are enhanced umbilical cord-derived adhesive stem cells, a preparation method therefor, and a use thereof. The enhanced umbilical cord-derived adhesive stem cells have an anti-inflammatory effect, a blood vessel regeneration effect, or a nerve regeneration effect, thereby being usable in a pharmaceutical composition or a cell therapeutic agent for treating or preventing various diseases. 1. Enhanced umbilical cord-derived adherent stem cells having one or more characteristics selected from the following (a) to (e):a) having a high expression level of one or more selected from the group consisting of COL1A1, IGFBP4, TAGLN, STC1, LRRC17, and IL33, as compared with bone marrow stem cells;b) having a low expression level of one or more selected from the group consisting of CCND1 SERPINE1, PRNP, and CYP1B1, as compared with bone marrow stem cells;c) maintaining the morphology of adherent fibroblasts during subcultured) having ability to differentiate into adipocytes, osteocytes, or chondrocytes: ande) having one or more surface antigen characteristics selected from the group consisting of CD200+, Tra-1-60−, CD3−, CD1a−, CD11c−, CD16−, CD86−, CD8a−, CD40−, CD141+CD61+, CD87+, MIC NB−, and SSEA4+.2. The enhanced umbilical cord-derived adherent stem cells of claim 1 , further having one or more characteristics selected from the following (f) to (i):f) having a high expression level of one or more selected from the group consisting of S100A10, BNIP3, IGFBP5, NDUFA4L2, DPYD, and SCARA3, as compared with those cultured under a normoxia condition;g) having a low expression level of one or more selected from the group consisting of IL8, ALDH1A1, DLC1, CTHRC1, and CPA4, as compared with those cultured under a normoxia condition;h) having a high expression level of one or more selected from the group consisting, of SNCA, DSG2, NRP2, and PLAT, as compared with bone marrow stem cells; andi) having a low expression level of one or more selected from the group consisting of ...

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Номер записи: 67
24-08-2017 дата публикации

Placenta-derived potential cells and preparing method thereof

Номер: US20170240856A1
Автор: Haochuan Wang, Jigang Zhang
Принадлежит: Shanghai Stemsan Biotechnology Co ltd

A method for culturing placental potential cell is provided, comprising steps of: (1) obtaining placental cells and/or tissue under aseptic condition; (2) inoculating the placental cells and/or the tissue in a culture medium for culturing, adding cell growth regulators to the culture medium, in such a manner that the placental potential cells grows to make the placental cells and/or the tissue into a proliferative state; (3) culturing the placental potential cells to make the placental potential cells proliferate continuously into cells with characteristics of stem cells. The present invention not only finds the source of human tissues, organs and the continuation of their function, i.e., regenerative potential cells; but also finds a medical and health longevity method, but also finds out the life materials to maintain and support the potential cells, so as to replace drugs with the living material.

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Номер записи: 68
13-11-2014 дата публикации

Method of Treating or Reducing EFP

Номер: US20140335072A1
Автор: Hart Susan G. Emeigh
Принадлежит: Auxilium Pharmaceuticals, Inc.

The present invention is directed to a method of treating or reducing EFP in a patient comprising administering one or multiple low dose injections of collagenase to an area affected by EFP. The invention encompasses methods wherein the dose of collagenase per injection is between about 50 to about 200 ABC units and/or wherein the concentration of collagenase is between about 50 to about 2000 ABC units/milliliter (ml). 1. A method of treating or reducing edematous fibrosclerotic panniculopathy (EFP) in a patient comprising administering at least one subdermal injection of collagenase to an area affected by EFP , wherein the dose of collagenase per injection is between about 5 to about 200 ABC units.2. The method of claim 1 , wherein a plurality of subdermal injections are administered at a plurality of injection sites.3. The method of claim 1 , wherein the concentration of collagenase administered is between about 50 to about 2000 ABC units per milliliter.4. The method of claim 1 , wherein each injection of collagenase is administered in a volume of about 0.5 ml or less.5. The method of claim 1 , wherein the total dose of collagenase administered is between about 5 to about 2000 ABC units.6. The method of claim 1 , wherein the dose of collagenase per injection is between about 5 to about 100 ABC units.7. The method of claim 1 , wherein the dose of collagenase per injection is between about 5 to about 50 ABC units.8Clostridium histolyticum.. The method of claim 1 , wherein the collagenase is purified from9. The method of claim 1 , wherein the collagenase is a recombinant collagenase.10Clostridium histolyticum. The method of claim 8 , wherein the collagenase purified from comprises collagenase I and collagenase II.11. The method of claim 5 , wherein the collagenase I and collagenase II are present at a 1:1 mass ratio.12. The method of claim 1 , wherein the collagenase is present in a pharmaceutical composition consisting essentially of collagenase and a ...

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Номер записи: 69
31-08-2017 дата публикации

Blends containing proteases

Номер: US20170247679A1
Автор: Johann-Peter Thalhofer, Markus Weber, Michaela Fischer, Werner Hoelke
Принадлежит: Roche Diagnostics Operations Inc

Described are compositions, in particular lyophilizates, containing proteolytic enzymes, and methods for producing the compositions. Typically these compositions contain one or more proteases with collagenase activity and a neutral protease, for example, thermolysin. The compositions are free of acetate salts. Surprisingly, such compositions can be dissolved in water more rapidly than lyophilized protease mixtures of the state of the art.

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Номер записи: 70
06-09-2018 дата публикации

METHOD OF ASSESSING AND TREATING CELLULITE

Номер: US20180250217A1
Автор: Davidson Jeffrey, Liu Genzhou, MCLANE Michael
Принадлежит:

The present disclosure relates to a method for rating the severity of cellulite on a thigh or buttock in a human subject by utilizing a photonumeric scale that provides reliable results from physician-to-physician and patient-to-patient. 1. A validated photonumeric scale for rating the severity of cellulite in an affected area of a human subject , the scale comprising:Not more than 10 but not less than 3 images showing the affected area of an example patient, the images being organized in different categories representing levels of severity based on a characteristic of cellulite;the characteristic being selected from the group consisting of the number, depth, size, width, diameter, and distribution of dimples; andwherein when the scale is employed by a plurality of users, at least 40% assign the subject's area of cellulite the same severity level.2. The scale of wherein the affected area is buttock.3. The scale of wherein the level of severity of the characteristic is represented by photographs of at least 3 different example human subjects.4. The scale of wherein there are 5 images representing 5 different categories.5. The scale of wherein the users are clinicians and provide the same severity level in at least 50% of the patients.6. The scale of wherein the affected area is thigh.7. The scale of wherein the images are to buttock and thigh scales depicted in .8. The scale of comprising a CR-PCSS scale.9. The scale of comprising a PR-PCSS scale.10. The scale of wherein when the scale is employed by a plurality of users claim 8 , at least 40% assign the subject's area of cellulite the same severity level.11. The scale of wherein when the scale is employed by a plurality of users claim 9 , at least 40% assign the subject's area of cellulite the same severity level.12. A method for rating the severity of cellulite in an affected area in a human subject claim 9 , comprising:a. selecting an affected area; andb. classifying, using images, the severity of the subject's ...

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Номер записи: 71
15-08-2019 дата публикации

DELIVERY OF THERAPEUTIC AGENTS BY A COLLAGEN BINDING PROTEIN

Номер: US20190249163A1
Автор: Gensure Robert C., Katikaneni Ranjitha, Koide Takaki, Matsushita Osamu, NISHI Nozomu, Philominathan Sagaya Theresa Leena, Ponnapakkam Tulasi, Sakon Joshua
Принадлежит:

Methods of delivering therapeutic agents by administering compositions including a bacterial collagen-binding polypeptide segment linked to the therapeutic agent to subjects in need of treatment with the therapeutic agent are provided. In these methods, the therapeutic agent is not a PTH/PTHrP receptor agonist or antagonist, basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF). The bacterial collagen-binding polypeptide segment delivers the agent to sites of partially untwisted or under-twisted collagen. Methods of treating collagenopathies using a composition including a collagen-binding polypeptide and a PTH/PTHrP receptor agonist are also provided. In addition, methods of treating hyperparathyroidism, and hair loss using compositions comprising a collagen binding polypeptide and a PTH/PTHrP receptor agonist are provided. Finally, methods of reducing hair regrowth by administering a composition including a collagen binding polypeptide and a PTH/PTHrP receptor antagonist are provided. 1. (canceled)2. (canceled)3Clostridium, Bacillus. A method of treating a collagenopathy comprising administering a composition comprising a bacterial collagen-binding polypeptide segment linked to a PTH/PTHrP receptor agonist to a subject , wherein the bacterial collagen-binding polypeptide segment delivers the agent to sites of partially untwisted or under-twisted collagen and wherein the bacterial collagen-binding polypeptide segment comprises a collagen-binding polypeptide derived from an M9 peptidase selected from the group consisting of and Vibrio , one of SEQ ID NOs: 13-34 or a fragment thereof , residues 34-158 of SEQ ID NO: 1 , a fragment of at least 8 consecutive amino acids from residues 34-158 of SEQ ID NO: 1 , or a peptide that is at least 90% identical to residues 34-158 of SEQ ID NO: 1 or SEQ ID NOs: 13-34.4. The method of claim 3 , wherein the PTH/PTHrP receptor agonist comprises residues 1-33 of SEQ ID NO: 1 claim 3 , PTH (SEQ ID NO: 7) claim 3 , ...

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Номер записи: 72
14-09-2017 дата публикации

IDENTITY AND PURITY OF TISSUE BIOPSIES

Номер: US20170261515A1
Автор: Benz Karin, Freudigmann Christian, GAISSMAIER Christoph, Hecky Jochen, Mollenhauer Jürgen
Принадлежит:

A method for the in vitro detection of cartilage tissue and/or for the in vitro determination of the purity of cartilage tissue includes: a) treating a tissue sample with a protease and b) testing the protease-treated tissue sample for the presence of protease-resistant fragments of type II collagen and/or type I collagen. Methods can be carried out for preparing a cartilage cell culture, and for preparing a cartilage cell-loaded implant. Protease-resistant fragments of type II collagen and/or type I collagen can be used for the in vitro detection of cartilage tissue and/or for the in vitro determination of the purity of cartilage tissue. A kit can be used for carrying out the methods. 1. A method for the in vitro detection of cartilage tissue and/or for the in vitro determination of the purity of cartilage tissue , comprising the following steps:a) treating a tissue sample with a protease andb) testing the protease-treated tissue sample for the presence of protease-resistant fragments of type II collagen and/or type I collagen.2. The method as claimed in claim 1 , wherein the tissue sample is a joint biopsy.3. The method as claimed in claim 1 , wherein superficial cartilage tissue claim 1 , mineralized cartilage tissue and/or bone tissue is removed from the tissue sample before step a) is carried out.4. The method as claimed in claim 1 , wherein the tissue sample is a tissue fragment of a cartilage/bone core biopsy.5. The method as claimed in claim 1 , wherein the protease is collagenase.6. The method as claimed in claim 1 , wherein the protease-resistant fragments of type II collagen and/or type I collagen are crosslinked collagen fragments.7. The method as claimed in claim 1 , wherein the protease-resistant fragments of type II collagen and/or type I collagen have crosslinks selected from the group comprising allysine crosslinks claim 1 , hydroxyallysine crosslinks claim 1 , dehydrohydroxylysinonorleucine crosslinks claim 1 , dehydrolysinonorleucine crosslinks ...

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Номер записи: 73
01-10-2015 дата публикации

USE OF COLLAGENASE TO TREAT GLAUCOMA

Номер: US20150273028A1
Автор: Honkanen Robert
Принадлежит: The Research Foundation for The State University of New York

Provided is a method of treatment for reducing fibrosis involving administering purified collagenase into an anterior chamber of an eye of a human patient. 1. A method of treatment for reducing fibrosis , the method comprising:administering an effective amount of purified collagenase into an anterior segment of an eye.2. The method of claim 1 , wherein the treatment is administered before or after glaucoma surgery.3. The method of claim 1 , wherein the anterior segment is a sub-Tenons space of the eye.4. The method of claim 1 , wherein the anterior segment is an episcleral space of the eye.5Clostridium histolyticum.. The method of claim 1 , wherein the purified collagenase is Clostridiopeptidase A derived from bacterium6. The method of claim 1 , wherein purified collagenase is administered alone or in conjunction with fluorescein dye.7. The method of claim 1 , wherein purified collagenase is administered in an absence of triamcinolone or other corticosteroids.8. The method of claim 1 , wherein the purified collagenase is injected in a dose comprising at least about 15 claim 1 ,000 SRC units/mg claim 1 , applied in one or more injections.9. The method of claim 1 , wherein the purified collagenase is injected in a volume of about 1.0 less than 100 microliters.10. The method of claim 1 , wherein the purified collagenase comprises one of collagenase I and collagenase II. This application is a U.S. National Phase entry of PCT/US2013/066589, filed Oct. 24, 2013, and claiming priority to U.S. Provisional Patent Application No. 61/717,837, filed on Oct. 24, 2012, the contents of which are incorporated herein by reference.1. Field of the InventionThe present invention relates generally to a method to reduce or remove fibrosis following glaucoma surgery involving administration of purified collagenase into a patient's eye.2. Description of the Related ArtGlaucoma is a leading cause of irreversible blindness. About 60.5 million people were affected with glaucoma in 2010, with ...

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Номер записи: 74
21-09-2017 дата публикации

LUCILIA SERICATA COLLAGENASE

Номер: US20170267988A1
Автор: Alipour Hamzeh, Dinparast Djadid Navid, Raz Abbasali, Zakeri Sedigheh
Принадлежит:

One complementary DNA (cDNA) encodes a collagenase enzyme of that includes an identified sequence. Optionally, the cDNA is applied to wound healing.

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Номер записи: 75
11-11-2021 дата публикации

METHODS FOR TREATING AGING AND SKIN DISORDERS USING NUCLEIC ACIDS TARGETING TYR OR MMP1

Номер: US20210348169A1
Автор: Cauwenbergh Gerard
Принадлежит: Phio Pharmaceuticals Corp.

The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal applications. 1. A method for treating a skin disorder comprising administering to a subject in need thereof a therapeutically effective amount of an isolated chemically modified double stranded nucleic acid molecule that is directed against a gene encoding Matrix metalloproteinase-1 (MMP1.23-. (canceled)4. The method of claim 1 , wherein the isolated double stranded nucleic acid molecule includes a double stranded region and a single stranded region claim 1 , wherein the region of the molecule that is double stranded is from 8-15 nucleotides long claim 1 , wherein the guide strand contains a single stranded region that is 4-12 nucleotides long claim 1 , wherein the single stranded region of the guide strand contains 3 claim 1 , 4 claim 1 , 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 claim 1 , 9 claim 1 , 10 claim 1 , 11 or 12 phosphorothioate modifications claim 1 , and wherein at least 40% of the nucleotides of the isolated double stranded nucleic acid molecule are modified.5. The method of claim 4 , wherein the isolated double stranded nucleic acid molecule further comprises a hydrophobic conjugate that is attached to the isolated double stranded nucleic acid molecule.6VibrioClostridium. The method of claim 1 , wherein the skin disorder is skin photo aging claim 1 , acne scarring claim 1 , cutaneous hyperpigmentation claim 1 , melasma claim 1 , skin lentigos claim 1 , chronic ulcers claim 1 , venous ulcers claim 1 , gangrene (and ) claim 1 , blistering skin disorders claim 1 , Stevens-Johnson syndrome claim 1 , or keloids.710-. (canceled)11. The method of claim 1 , wherein the double stranded nucleic acid molecule is in a composition formulated for topical delivery claim 1 , a composition formulated for delivery to the skin claim 1 , a composition formulated for intradermal injection claim 1 , and/or a composition ...

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Номер записи: 76
08-10-2015 дата публикации

FUSION PROTEINS OF COLLAGEN-BINDING DOMAIN AND PARATHYROID HORMONE

Номер: US20150284701A1
Автор: Gensure Robert C., Matsushita Osamu, Ponnapakkam Tulasi, Sakon Joshua
Принадлежит:

Fusion proteins containing active agonist or antagonist fragments of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) coupled to a collagen-binding domain are presented. The fusion proteins can be used to promote bone growth, to promote hair growth, to prevent cancer metastasis to bone, to promote immune reconstitution with a bone marrow stem cell transplant, to promote mobilization of bone marrow stem cells for collection for autologous stem cell transplant, and to treat renal osteodystrophy. Pharmaceutical agents comprising a collagen-binding polypeptide segment linked to a non-peptidyl PTH/PTHrP receptor agonist or antagonist are also presented. 160-. (canceled)61. A composition comprising:a collagen-binding polypeptide segment covalently linked to a PTH/PTHrP receptor antagonist; wherein the collagen-binding polypeptide segment is a ColH or ColG bacterial collagen binding polypeptide segment or a segment of a collagenase, wherein the PTH/PTHrP receptor antagonist comprises a peptide selected from the group consisting of residues 7-14 of SEQ ID NO: 7, residues 7-33 of SEQ ID NO: 7, residues 7-34 of SEQ ID NO: 7 and residues 7-34 of SEQ ID NO: 8, and wherein the collagen-binding polypeptide segment comprises residues 38-158 of SEQ ID NO: 1, a fragment of at least 8 consecutive amino acids from residues 38-158 of SEQ ID NO: 1 or is at least 90% identical to residues 38-158 of SEQ ID NO:1.62. The composition of claim 61 , wherein the collagen-binding polypeptide segment and the PTH/PTHrP receptor antagonist are chemically cross-linked to each other or are polypeptide portions of a fusion protein.63. The composition of claim 61 , wherein the PTH/PTHrP receptor antagonist is a polypeptide and the N-terminus of the collagen-binding polypeptide segment is linked directly or through a linker polypeptide segment to the C-terminus of the PTH/PTHrP receptor antagonist polypeptide.64. The composition of claim 61 , wherein the composition further 38- ...

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Номер записи: 77
18-11-2021 дата публикации

Methods, apparatuses and systems for adolescent idiopathic scoliosis treatment

Номер: US20210353723A1
Автор: Phillip Douglas Kiester
Принадлежит: Individual

The METHODS, APPARATUSES AND SYSTEMS FOR ADOLESCENT IDIOPATHIC SCOLIOSIS TREATMENT (hereinafter “AIST”) disclosed herein leverage the biomechanical cause of AIS in the ventral portion of the interspinous ligament to treat AIS. In various embodiments, the AIST include chemically lysing the abnormal tethering structure, thereby allowing the AIS spine to decrease its deformity with usual day-to-day activities, without bracing and without instrumented and/or fusion surgery.

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Номер записи: 78
29-09-2016 дата публикации

POLYMER NANOCOMPOSITES FOR EARLY DIAGNOSIS OF DISEASES

Номер: US20160282358A1
Автор: ANDREW Jennifer
Принадлежит: UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INC.

Disclosed herein is a composition comprising a crosslinked hydrogel; where the hydrogel comprises a polymer having a cleavable bond along a backbone of the polymer, along a substituent that undergoes crosslinking, or along the backbone of the polymer and along the substituent that undergoes crosslinking; where the cleavable bond is operative to be cleaved by an enzyme released in the body of a living being; and a semiconducting quantum dot that emits light in the visible portion of the electromagnetic spectrum. 1. A composition comprising:a crosslinked hydrogel; where the hydrogel comprises a polymer having a cleavable bond along a backbone of the polymer, along a substituent that undergoes crosslinking, or along the backbone of the polymer and along the substituent that undergoes crosslinking; where the cleavable bond is operative to be cleaved by an enzyme released in the body of a living being; anda detectable nanoparticle that is optically or magnetically detectable.2. The composition of claim 1 , where the detectable nanoparticle is a semiconducting quantum dot that emits light in the visible portion of the electromagnetic spectrum.3. The composition of claim 1 , where the cleavable bond is an enzymatically cleavable peptide linker.4. The composition of claim 1 , where the hydrogel comprises xanthan gum claim 1 , gum arabic claim 1 , guar gum claim 1 , locust bean gum claim 1 , cellulose derivatives claim 1 , carboxymethyl cellulose claim 1 , hydroxypropyl cellulose claim 1 , alginate claim 1 , starch claim 1 , polyvinyl alcohol claim 1 , polyacrylamide claim 1 , poly(N-isopropylacrylamide) claim 1 , polyalkylene glycol claim 1 , poly(2-oxazoline) claim 1 , polyethylenimine claim 1 , polyethylene glycol claim 1 , polypropylene glycol claim 1 , poly(acrylic acid) claim 1 , polystyrenesulfonic acid claim 1 , or a combination comprising at least one of the foregoing hydrogels.5. The composition of claim 1 , where the hydrogel is blended or copolymerized with a ...

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Номер записи: 79
20-08-2020 дата публикации

BLENDS CONTAINING PROTEASES

Номер: US20200263160A1
Автор: Fischer Michaela, Hoelke Werner, Thalhofer Johann-Peter, Weber Markus
Принадлежит: ROCHE DIAGNOSTICS OPERATIONS, INC.

Described are compositions, in particular lyophilizates, containing proteolytic enzymes, and methods for producing the compositions. Typically these compositions contain one or more proteases with collagenase activity and a neutral protease, for example, thermolysin. The compositions are free of acetate salts. Surprisingly, such compositions can be dissolved in water more rapidly than lyophilized protease mixtures of the state of the art. 1(a) preparing a homogeneous solution of an acetate-free preparation of thermolysin in an aqueous acetate-free low-salt solution, wherein the low-salt solution comprises a buffer salt buffering in the range of about pH 6 to about pH 8.5, wherein the low-salt solution further comprises calcium chloride, and wherein the aggregate concentration of salt(s) in the low-salt solution is in the range of about 1 mM to about 250 mM;(b) adding sodium chloride to the homogeneous solution of step (a) and dissolving the sodium chloride, thereby making a solution, wherein the solution comprises the buffer salt buffering in the range of about pH 6 to about pH 8.5, and wherein the solution further comprises the thermolysin at a concentration in the range of about 0.5 mg/ml to about 5 mg/ml, and calcium chloride, and the conductivity of the solution is in the range of about 20 mS/cm to about 23 mS/cm, wherein the buffer salt is a compound selected from the group consisting of BES (N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), Tris (2-Amino-2-hydroxymethyl)propane-1,3-diol), BisTris (Bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane), BisTris propane (1,3-bis(tris(hydroxymethyl)methylamino)propane), HEPES (N-(2-hydroxyethyl)-piperazine-N′-2-ethanesulfonic acid), MES (2-(Nmorpholino) ethanesulfonic acid), MOPS (3-(Nmorpholino) propanesulfonic acid), MOPSO (3-morpholino-2-hydroxypropanesulfonic acid), PIPES (Piperazine-1,4-bis(2-ethanesulfonic acid)), TAPS (N-Tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid), TES (N-Tris(hydroxymethyl) ...

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Номер записи: 80
25-11-2021 дата публикации

METHODS FOR EVALUATING TUMOR CELL SPHEROIDS USING 3D MICROFLUIDIC CELL CULTURE DEVICE

Номер: US20210363595A1
Автор: Aref Amir, Barbie David, Ivanova Elena, Jenkins Russell W., Paweletz Cloud P.
Принадлежит: Dana-Farber Cancer Institute, Inc.

Provided herein are methods for evaluating tumor cell spheroids in a three-dimensional microfluidic device by determining changes in the relative levels of live cells and dead cells in aliquots cultured under different conditions. Methods described herein allow ex vivo recapitulation of the tumor microenvironment such that the in vivo effectiveness of a test compound in treating tumor tissue may be predicted. 1. A method for evaluating tumor cell spheroids in a three-dimensional microfluidic device , the method comprising:obtaining tumor spheroids from an enzyme treated tumor sample,suspending a first aliquot of the tumor spheroids in biocompatible gel;suspending a second aliquot of the tumor spheroids in biocompatible gel;placing the first aliquot of the tumor spheroids in biocompatible gel in a first three-dimensional device,contacting the first aliquot with a first fluorophore dye selective for dead cells, the first fluorophore dye emitting fluorescence at a first wavelength when bound to a dead cell,contacting the first aliquot with a second fluorophore dye selective for live cells, the second fluorophore dye emitting fluorescence at a second wavelength different from the first wavelength when bound to a live cell,measuring total fluorescence emitted by each of the first and second fluorophore dyes in the first aliquot,culturing the second aliquot in a second three-dimensional device,contacting the second aliquot with the first fluorophore dye,contacting the second aliquot with the second fluorophore dye, wherein the contacting of the second aliquot with the first fluorophore dye and second fluorophore dye is carried out at least 24 hours after the contacting of the first aliquot with the first fluorophore dye and second fluorophore dye,measuring total fluorescence emitted by each of the first and second fluorophore dyes in the second aliquot,wherein an increase or decrease in the ratio of live cells to dead cells in each of the aliquots may be assessed.2. The ...

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Номер записи: 81
06-10-2016 дата публикации

COMPOSITION FOR DISPERSING BIOLOGICAL TISSUE

Номер: US20160289662A1
Автор: KAWAMURA Seiko, KOBAYASHI Hisayuki, Miyagawa Isao
Принадлежит: KURASHIKI BOSEKI KABUSHIKI KAISHA

The purpose of the present invention is to acquire a highly proliferative cell at a high efficiency from a sample derived from a biological tissue. Provided is a composition for dispersing a biological tissue, wherein a solution formulation of the composition has a collagenase activity of 0.30-10 U/mL, said collagenase activity being determined by a method for measuring FALGPA-decomposing activity, and a trypsin activity of 0-30 U/mL at a formulation concentration of the composition, said trypsin activity being determined by a method for measuring BASE hydrolytic activity. 1. A composition for dispersing biological tissue , wherein a collagenase activity of the composition in a formulation solution is 0.30 U/mL to 10 U/mL as determined by a method for measuring FALGPA-degrading activity , and wherein a trypsin activity of the composition in the formulation solution is 0 U/mL to 30 U/mL as determined by a method for measuring BAEE hydrolytic activity.2. The composition according to claim 1 , for a drug assessment.3. The composition according to claim 1 , wherein the biological tissue is cancer tissue.4. A method for obtaining a cell derived from biological tissue claim 1 , comprising treating a sample derived from the biological tissue with the composition according to .5. A method for evaluating a cell culture result claim 1 , wherein the cell is treated with the composition according to .6. The method according to claim 5 , wherein the cell culture result is a result from two-dimensional culture.7. The method according to claim 5 , wherein the cell culture result is a result from three-dimensional culture.8. The method according to claim 7 , wherein the three-dimensional culture is carried out in a droplet gel.9. A kit for carrying out the method according to claim 4 , comprising said composition for dispensing biological tissue. The present invention relates to a composition for dispersing biological tissue. The present invention also relates to a method for ...

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Номер записи: 82
18-10-2018 дата публикации

COMPOSITION FOR RAPIDLY SEPARATING ADIPOSE TISSUE-DERIVED STROMAL CELLS

Номер: US20180298342A1
Автор: Chang Je-Ken, Chen Chung-Hwan, Ho Mei-Ling, Wang Yao-Hsien
Принадлежит: KAOHSIUNG MEDICAL UNIVERSITY

The present invention provides a composition for isolating adipose-derived stromal cells, which comprises a Type I collagenase of 0.5-8% (v/v); a Trypsin of 0.1-0.6% (v/v); and a metal ion chelating agent of 0.01-0.2% (v/v). The present invention further provides a method for isolating adipose-derived stromal cells, which method comprises obtaining an adipose tissue; treating the adipose tissue with the composition of the present invention; centrifuging the adipose tissue; and isolating the adipose tissue to obtain the adipose-derived stromal cells. The present invention facilitates rapid isolation of mesenchymal stromal cells within a short period of time in operating rooms and can be applied to regenerative medicine in the future. 1. A composition for isolating adipose-derived stromal cells , which comprises a Type I collagenase of 0.5-8% (v/v); a Trypsin of 0.1-0.6% (v/v); and a metal ion chelating agent of 0.01-0.2% (v/v).2. The composition according to claim 1 , wherein the metal ion chelating agent is selected from ethylenediaminetetraacetic acid (EDTA) or sodium salts thereof claim 1 , ethylene glycol-bisaminoethyl ether tetraacetic acid (EGTA) or sodium salts thereof claim 1 , diethylene triamine pentaacetic acid (DTPA) or sodium salts thereof claim 1 , polyphosphates claim 1 , organic phosphates claim 1 , phosphates claim 1 , polyacrylates claim 1 , organic phosphates claim 1 , sodium gluconate claim 1 , or mixtures thereof.3. The composition according to claim 2 , wherein the metal ion chelating agent is EDTA.4. A method for isolating adipose-derived stromal cells claim 2 , which comprises the steps of:(a) obtaining an adipose tissue;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(b) adding the composition according to , homogenizing and allowing for reaction to obtain a digested tissue mixture, wherein the composition comprises a Type I collagenase of 0.5-8% (v/v); a Trypsin of 0.1-0.6% (v/v); and a metal ion chelating agent of 0.01-0.2% (v/v);'}(c) ...

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Номер записи: 83
12-11-2015 дата публикации

System and Method for Modulation of Cardiac Tissue

Номер: US20150320845A1
Автор: Shivkumar Kalyanam
Принадлежит:

The present invention provides compositions, systems, and methods for modulation of cardiac tissue. In one embodiment, the invention provides for bioenzymatic ablation of cardiac tissue. In certain embodiments, the present invention provides for application of collagenase or other therapeutic agents to digest targeted cardiac tissue. 1. A method of modulating a region of cardiac tissue , comprising contacting at least a portion of the region of cardiac tissue with an effective amount of at least one therapeutic agent selected from the group consisting of a protease , a collagenase , a lipase , and a detergent.2. The method of claim 1 , wherein the method reduces the size of border zones of scar tissue claim 1 , thereby at least partially homogenizing the scar tissue.3. The method of claim 1 , wherein the therapeutic agent comprises a collagenase solution.4. The method of claim 1 , wherein the collagenase acts upon type IV collagen.5. The method of claim 1 , wherein the collagenase is purified collagenase.6. The method of claim 1 , wherein the at least one therapeutic agent removes fat from the region.7. The method of claim 1 , wherein the region includes surviving myocytes.8. The method of claim 1 , wherein the region is a border zone region.9. The method of claim 8 , wherein the region is an area of low-amplitude claim 8 , delayed multicomponent electric activity.10. The method of claim 3 , wherein the concentration of collagenase in the collagenase solution is between 0.001-1%.11. The method of claim 3 , wherein the amount of collagenase in the collagenase solution is between 1-1000 U/mL.12. The method of claim 1 , wherein the at least one therapeutic agent is delivered via a catheter.13. The method of claim 12 , wherein the catheter is an ablation catheter.14. The method of claim 1 , comprising using electroanatomical mapping to define the region prior to contacting at least a portion of the region with the therapeutic agent.15. The method of claim 1 , wherein ...

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Номер записи: 84
03-11-2016 дата публикации

BLENDS CONTAINING PROTEASES

Номер: US20160319268A1
Автор: Fischer Michaela, Hoelke Werner, Thalhofer Johann-Peter, Weber Markus
Принадлежит:

Described are compositions, in particular lyophilizates, containing proteolytic enzymes, and methods for producing the compositions. Typically these compositions contain one or more proteases with collagenase activity and a neutral protease, for example, thermolysin. The compositions are free of acetate salts. Surprisingly, such compositions can be dissolved in water more rapidly than lyophilized protease mixtures of the state of the art. 1. A method for producing a solid composition comprising the steps of:preparing a homogeneous solution of an acetate-free preparation of a neutral protease (NP) in an aqueous acetate-free, low-salt solution, wherein the low-salt solution has an aggregate concentration of salt(s) in the range of about 1 mM to about 250 mM;adding a neutral salt to the homogeneous solution and dissolving the neutral salt, thereby making a stabilized solution, wherein the stabilized solution additionally comprises a buffer salt buffering in a range of about pH 6 to about pH 8.5, and wherein the stabilized solution further comprises calcium chloride;mixing the stabilized solution with an acetate-free preparation of one or more proteolytic enzymes with collagenase activity (C) and making a homogeneous solution; andfreeze-drying the homogeneous solution, thereby obtaining the solid composition.2Bacillus thermoproteolyticus.. The method according to claim 1 , wherein the neutral protease is thermolysin from3. The method according to claim 1 , wherein a weight/weight ratio of the neutral protease versus all proteases present in the composition (NP/(NP+C)) is in a range of about 1 to about 25.4. The method according to claim 1 , wherein the neutral salt is sodium chloride and a weight/weight ratio of all proteases present in the composition versus sodium chloride ((NP+C)/NaCl) is in a range of about 0.1 to about 5.5. The method according to claim 1 , wherein a weight/weight ratio of all proteases present in the composition versus calcium chloride ((NP+C)/ ...

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Номер записи: 85
02-11-2017 дата публикации

New process for the production and purification of the collagenase enzyme from vibrio alginolyticus

Номер: US20170314005A1
Автор: Christian Cuppari, Giovanni Gennari, Michele Caputo, Susanna Vaccaro
Принадлежит: Fidia Farmaceutici SpA

The present invention claims a novel process for the production and purification of microbial collagenase (Microbial Collagenase EC 3.4.24.3) produced by the non-pathogenic aerobic bacterium Vibrio alginolyticus chemovar. iophagus (NCIMB Number: 11038, synonym LMG 3418, hereinafter called Vibrio alginolyticus ), which said process provides high production levels of collagenase with a stable, reproducible, cheap fermentation process. The collagenase produced from Vibrio alginolyticus according to the process described herein also presents a specific activity superior to that of other microbial collagenases, is stable in aqueous solution, and can be frozen without significant damage. A further subject of the present invention is pharmaceutical compositions containing collagenase obtained according to the production and purification process described, for the purpose of therapeutic treatment of disorders characterised by collagen accumulation or for the treatment of blemishes/imperfections that benefit from reducing local collagen accumulations.

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Номер записи: 86
17-11-2016 дата публикации

COMPOSITIONS AND METHODS FOR TREATING FIBROTIC MYOPATHY CONDITIONS USING COLLAGENASE

Номер: US20160331817A1
Автор: Raven Raymond B.
Принадлежит:

Compositions and methods for treating fibrotic myopathy in a subject. 1. A method of treating fibrotic myopathy in a subject , the method comprising the step of:administering an effective amount of a composition comprising collagenase to a fibrotic area of a muscle of the subject, 'the composition is administered sub-dermally to the fibrotic area in at least one injection.', 'wherein'}2. The method according to claim 1 , wherein the anti-fibrotic agent is selected from the group consisting of pancreatic elastase claim 1 , elastase-2a claim 1 , elastase-2b claim 1 , neutrophil elastase claim 1 , proteinase-3 claim 1 , endogenous vascular elastase claim 1 , cathepsin G claim 1 , mast cell chymase claim 1 , mast cell tryptase claim 1 , plasmin claim 1 , thrombin claim 1 , granzyme B claim 1 , cathepsin S claim 1 , cathepsin K claim 1 , cathepsin L claim 1 , cathepsin B claim 1 , cathespin C claim 1 , cathepsin H claim 1 , cathespin F claim 1 , cathepsin G claim 1 , cathepsin O claim 1 , cathepsin R claim 1 , cathepsin V (cathepsin 12) claim 1 , cathepsin W claim 1 , calpin 1 claim 1 , calpin 2 claim 1 , chondroitinase ABC claim 1 , chondroitinase AC claim 1 , hyaluronidase claim 1 , chymopapain claim 1 , chymotrypsin claim 1 , legumain claim 1 , cathepsin Z (cathepsin X) claim 1 , cathepsin D claim 1 , cathepsin E claim 1 , microbial collagenases claim 1 , matrix metalloproteinases claim 1 , ADAMTS-1 claim 1 , ADAMTS-2 claim 1 , ADAMTS-3 claim 1 , ADAMTS-4 (aggrecanase-1) claim 1 , ADAMTS-5(aggrecanase-2) claim 1 , ADAMTS-14 claim 1 , papain claim 1 , subtilisin claim 1 , subtilisin A claim 1 , heparanase claim 1 , and combinations thereof.3. The method according to claim 1 ,wherein the collagenase selected from the group consisting of microbial collagenases, mammalian collagenases, and combinations thereof.4. The method according to claim 3 ,{'i': 'Clostridium histolyticum.', 'wherein the collagenase is derived from'}5. The method according to claim 4 ,{'i': ' ...

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Номер записи: 87
08-11-2018 дата публикации

AGENTS AND METHODS FOR TREATING AND PREVENTING SEBORRHEIC KERATOSIS

Номер: US20180320132A1
Автор: Lee Sam, Mandinova Anna I., Neel Victor A.
Принадлежит: The General Hospital Corporation

Provided herein are methods and assays for isolating and culturing seborrheic keratosis cells ex vivo. Also provided herein are screening assays using cultured seborrheic keratosis cells and methods for treating seborrheic keratosis in a subject. 1. A method for inducing apoptosis in a seborrheic keratosis cell , the method comprising contacting a seborrheic keratosis cell with an effective amount of a composition that inhibits Akt signaling , thereby inducing apoptosis in the cell.2. The method of claim 1 , wherein the effective amount of the composition does not substantially affect the survival of normal keratinocytes.3. The method of claim 1 , wherein the composition comprises a small molecule claim 1 , a peptide inhibitor or an RNAi molecule.4. The method of claim 1 , wherein the composition comprises an Akt-1 and/or an Akt-2 inhibitor.5. The method of claim 1 , wherein the Akt inhibitor is an ATP-competitive Akt inhibitor.6. A method for treating a seborrheic keratosis in a subject claim 1 , the method comprising administering a composition comprising a therapeutically effective amount of an siRNA that targets Akt to a subject having seborrheic keratosis.7. The method of claim 6 , wherein the composition is applied topically or administered systemically.8. The method of claim 6 , wherein the therapeutically effective amount of the composition does not substantially affect the survival or normal keratinocytes.9. The method of claim 6 , wherein the composition further comprises a pharmaceutically acceptable carrier. This application is a Continuation of U.S. application Ser. No. 15/482,899 filed on Apr. 10, 2017, which is a continuation of U.S. application Ser. No. 15/254,344, filed on Sep. 1, 2016, which is a Divisional of U.S. application Ser. No. 14/395,737 (now U.S. Pat. No. 9,458,462), filed on Oct. 20, 2014, which is a 35 U.S.C. 371 National Stage Application of International Application No. PCT/US2013/038358, filed on Apr. 26, 2013, which designates the ...

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Номер записи: 88
24-11-2016 дата публикации

REDUCTION OF ADIPOSE TISSUE

Номер: US20160339088A1
Автор: BRONSTHER BURTON, BRONSTHER ELLYN, ERWIN JACOB T., WEGMAN EDWIN H.
Принадлежит:

The amount of adipose tissue, including lipomas, at selected locations in the body is reduced by introducing collagenase or collagenase plus another proteinase into the tissue. 1. A method of reducing the amount of adipose tissue at selected locations in the body which consists of introducing into said tissue effective amounts of an enzyme and a pharmaceutically acceptable carrier , wherein the enzyme is purified collagenase in the substantial absence of another proteinase.2. A method of reducing the amount of adipose tissue at selected locations in the body wherein said method comprises introducing into said tissue a composition consisting of an effective amount of an enzyme and a pharmaceutically acceptable carrier , wherein the enzyme is purified collagenase.3. A method of reducing the amount of adipose tissue at selected locations in the body consisting of introducing into said tissue a composition consisting of an effective amount of purified collagenase and a pharmaceutically acceptable carrier.4. A method according to claim 3 , wherein said collagenase is injected into said adipose tissue.5. A method according to claim 4 , wherein said carrier is a liquid.6. A method according to claim 5 , wherein said carrier is aqueous.7. A method according to claim 6 , wherein said adipose tissue is injected at a multiplicity of closely spaced sites.8. A method according to claim 6 , wherein the collagenase is introduced in the amount of from about 5 to about 150 ABC units collagenase per gram of adipose tissue treated.9. A method according to claim 8 , wherein said amount of collagenase is from about 10 to about 100 ABC units collagenase per gram of adipose tissue treated.10. A method according to claim 3 , wherein the collagenase is injected in a liquid pharmaceutically acceptable carrier in a concentration of from 50 to about 5 claim 3 ,000 ABC units per mL.11. A method according to claim 3 , wherein the collagenase is injected in a liquid pharmaceutically acceptable ...

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Номер записи: 89
23-11-2017 дата публикации

Treatment Method and Product for Uterine Fibroids using Purified Collagenase

Номер: US20170333356A1
Автор: Leppert Phyllis Carolyn, Taylor Darlene K., Wegman Thomas L.
Принадлежит:

The invention relates to compositions and methods for treating uterine fibroids, wherein a uterine fibroid treatment agent comprising collagenase in an amount effective to cause shrinkage of uterine fibroids is injected or inserted into the uterine fibroid. 1. A method for the treatment of uterine fibroids , said method comprising: providing an injectable or insertable formulation that comprises a uterine fibroid treatment agent in an amount effective to cause shrinkage of uterine fibroids; and injecting or inserting said formulation into the uterine fibroid , wherein the uterine fibroid treatment agent is collagenase.2. The method of claim 1 , wherein the collagenase is obtained from a mammalian claim 1 , crustacean claim 1 , fungal or bacterial source.3. The method of claim 2 , wherein the collagenase is obtained from a bacterial source.4Clostridium.. The method of claim 3 , wherein the collagenase is obtained from5ClostridiumClostridium histolyticum.. The method of claim 4 , wherein the is6. The method of claim 5 , wherein the collagenase is a mixture of collagenase I and collagenase II.7. The method of claim 6 , wherein the collagenase I and collagenase II are present in a mass ration of about 0.5 to about 1.5.8. The method of claim 1 , wherein about 0.06 mg to about 1 mg collagenase is administered per cmof tissue to be treated.9. The method of claim 8 , wherein about 0.1 mg to about 0.8 mg collagenase is administered per cmof tissue to be treated.10. The method of claim 8 , wherein about 0.2 mg to about 0.6 mg collagenase is administered per cmof tissue to be treated.11. The method of claim 1 , wherein said formulation is injected or inserted into said fibroid transabdominally.12. The method of claim 1 , wherein said formulation is injected or inserted into said fibroid transvaginally.13. The method of claim 1 , wherein said formulation is injected or inserted into said fibroid under image guidance.14. The method of claim 13 , wherein said image is at least ...

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Номер записи: 90
15-11-2018 дата публикации

METHOD OF PRODUCING COLLAGENASE

Номер: US20180327731A1
Автор: Berbaum Michael, Dziadosz Jason, Hanna John, Shanafelt Daniel, Sheaffer Christine A.
Принадлежит:

The present invention relates to the fields of collagenase production and collagenase products, and particularly to improving the reproducibility, purity, and stability of collagenase I and collagenase II compositions, where the compositions are pure to at least 95% by area as measured by reverse phase high pressure liquid chromatography (RP-HPLC) and essentially free of neutral protease. 1. A drug product , comprising isolated and purified collagenase wherein the drug product is essentially free of neutral protease.2. The drug product of wherein the product comprises less than about 100 ng neutral protease per mg of the product.3. The drug product of wherein the product comprises less than about 75 ng neutral protease per mg of the product.4. The drug product of wherein the product comprises less than about 50 ng neutral protease per mg of the product.5. The drug product of wherein the product comprises less than about 25 ng neutral protease per mg of the product.6C. histolyticum.. The drug product of wherein the collagenase comprises collagenase I and collagenase II derived from7. The drug product of wherein the collagenase is at least one of collagenase I and collagenase II.8. The drug product of wherein the collagenase I and collagenase II are present in an approximate 1:1 ratio.9C. histolyticum. Isolated and purified collagenase I obtained or derived from wherein the collagenase I is essentially free of neutral protease.10. The collagenase I of wherein the collagenase I comprises no detectable amount of neutral protease.11. The collagenase I of wherein it comprises less than about 1000 ng neutral protease per mg of the collagenase I.12. The collagenase I of wherein it comprises less than about 500 ng neutral protease per mg of the collagenase I.13C. histolyticum. A method for isolation and purification of collagenase I and collagenase II obtained or derived from claim 9 , comprising controlling for a metal level during the purification of collagenase I and ...

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Номер записи: 91
15-11-2018 дата публикации

KITS AND METHODS FOR PREDICTION AND TREATMENT OF PREECLAMPSIA

Номер: US20180328937A1
Автор: Chaemsaithong Piya, Chaiworapongsa Tinnakorn, Hassan Sonia S., Romero Roberto, Tarca Adi L.
Принадлежит:

Biomarkers tests which can be used to predict a positive or negative risk of preeclampsia are described. More specifically, a panel of biomarkers including MMP-7 and gpIIbIIIa, described. The test is useful to predict preeclampsia when a biological sample is obtained between the 16th and 22nd week of pregnancy. Prediction later in pregnancy can be achieved by a combination of Siglec-6, Activin A, ALCAM, and/or FCN2. 1. A kit for predicting preeclampsia in a pregnant female comprising:(i) an array that measures MMP-7 and/or Siglec-6, and(ii) instructions that (a) direct assaying a sample obtained from the pregnant female for MMP-7 and/or Siglec-6 and (b) provide reference levels to predict a positive risk of preeclampsia in the pregnant female based on the assaying.2. A kit of wherein the array measures MMP-7.3. A kit of wherein the instructions direct that the sample be obtained between the 16and 22week of the pregnant female's gestation.4. A kit of wherein the array comprises one or more wells coated with MMP-7 binding ligands.5. A kit of comprising instructions that direct use of the MMP-7 measurement to predict preeclampsia risk.6. A kit of wherein the predicted preeclampsia is early onset preeclampsia.7. A kit of wherein the predicted preeclampsia is associated with maternal vascular underperfusion.8. A kit of wherein the array measures MMP-7 in combination with gpIIbIIIa.9. A kit of wherein the instructions direct that the sample be obtained between the 16and 22week of the pregnant female's gestation.10. A kit of wherein the array comprisesi) one or more well coated with MMP-7 binding ligands andii) one or more wells coated with gpIIbIIIa binding ligands.11. A kit of comprising instructions that direct use of the MMP-7 and gpIIbIIIa measurements to predict preeclampsia risk.12. A kit of wherein the predicted preeclampsia is early onset preeclampsia.13. A kit of wherein the array measures Siglec-6.14. A kit of wherein the instructions direct that the sample be ...

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Номер записи: 92
15-10-2020 дата публикации

HYALINE CARTILAGE SHAPING

Номер: US20200323548A1
Автор: Dinger Fred, Frazier Andrew
Принадлежит: Aerin Medical Inc.

Disclosed embodiments include devices and methods for shaping, bending, and/or volumetrically reducing rigid cartilaginous structures, such as hyaline cartilage in the septum. In the case of septal cartilage, shaping, bending, or reducing the cartilage would be useful for reducing nasal obstruction or to improve the cosmetic appearance of the nose. 1. A method for modifying a nasal septum of a subject's nose without forming an incision or removing tissue , the method comprising:injecting a substance under nasal mucosa and into contact with cartilage of the nasal septum, wherein the substance is configured to modify a property of the cartilage, and wherein the substance is selected from the group consisting of collagenase, hyaluronidase, tosyl lysyl chloromethane, trypsin, and trypsin/EDTA;inserting an elongate treatment element of a bipolar radiofrequency energy delivery device into the subject's nose, wherein the elongate treatment element comprises two rows of bipolar electrodes;applying force to the nasal septum with the elongate treatment element, to change a shape of the cartilage of the nasal septum;applying radiofrequency energy to the cartilage of the nasal septum at a selected tissue depth by transmitting the radiofrequency energy from a first row of the two rows of bipolar electrodes to a second row of the two rows, while continuing to apply force to the nasal septum with the elongate treatment element; andremoving the elongate treatment element from the subject's nose, wherein the shape of the cartilage of the nasal septum remains changed after the elongate treatment element is removed.2. (canceled)3. The method of claim 1 , wherein the substance is configured to soften the cartilage of the nasal septum.4. The method of claim 1 , wherein the substance is configured to dissolve proteoglycan structures of the cartilage.5. The method of claim 1 , wherein the substance comprises about 0.5 ml to about 2.5 ml of collagenase at a concentration of about 1 mg/ml ...

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Номер записи: 93
01-12-2016 дата публикации

THERMOSENSITIVE HYDROGEL COLLAGENASE FORMULATIONS

Номер: US20160346367A1
Автор: Wegman Thomas L., Yu Bo
Принадлежит: BioSpecifics Technologies Corp.

It is an object of the present disclosure to provide a formulation for injectable collagenase which will have extended residence time for the drug at the therapeutic targeted area for the indication being treated. It is a further object of the disclosure to provide a slow release formulation for collagenase which is compatible with the active ingredient and does not adversely affect its activity. Still a further object of the disclosure is to provide an injectable formulation for collagenase which can be effectively administered to a patient with a small size needle without exhibiting pregelation, which would interfere with the ability to deliver the required dose for treatment. 1. A sterile formulation for injection comprising a thermosensitive hydrogel and an effective amount of collagenase said formulation capable upon injection into a therapeutic target site in a subject having need of collagenase treatment , of providing to said site free , active collagenase and a gel capable of slow release of active collagenase over an extended period.2. The sterile formulation of which can be administered through a syringe fitted with a 28G½ needle without pregelation in the needle on injection.3. The sterile formulation of wherein the syringeability or the compatibility has been modified by the addition to the formulation of tris (hydroxymethyl) amino methane.4. The sterile formulation of wherein said thermosensitive hdyrogel is a triblock polymer.5. The sterile formulation of wherein said triblock polymer hydrogel is a poly (DL-lactic acid-co-glycolic acid) and poly (ethylene glycol) polymer of the structure PLGA-PEG-PLGA.6. The sterile formulation of wherein said collagenase is a 1:1 mixture of Aux I and Aux II collagenases derived from clostridium histolyticum.7. The sterile formulation of which is capable of forming a gel upon administration and entrapping at least about 80% of said collagenase.8. The sterile formulation of wherein said slow release of a major portion ...

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Номер записи: 94
30-11-2017 дата публикации

METALLOPROTEASES AND USES THEREOF

Номер: US20170342352A1
Автор: Bjerre Jeannette, Gjermansen Morten, Oestergaard Peter R.
Принадлежит: NOVOZYMES A/S

The present invention relates to metalloproteases and the use thereof in cleaning processes, such as laundry and dish wash. The invention also relates to detergent compositions and cleaning compositions comprising a metalloprotease. 1. An isolated polypeptide having protease activity selected from the group consisting of:a) a polypeptide having at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity, at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99.1% sequence identity, at least 99.2% sequence identity, at least 99.3% sequence identity, at least 99.4% sequence identity, at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity or even 100% sequence identity to the mature polypeptide of SEQ ID NO: 2, or to the mature polypeptide of SEQ ID NO: 4;b) a polypeptide encoded by a polynucleotide that hybridizes under high stringency conditions (i) with the mature polypeptide coding sequence of SEQ ID NO: 1 or SEQ ID NO: 3 or (ii) with the full-length complementary strand of (i);c) a polypeptide encoded by a polynucleotide having at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity, at least 91% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99%, at least 99.1% sequence identity, at least 99.2% sequence identity, ...

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Номер записи: 95
29-11-2018 дата публикации

Collagenase-derived peptides promote tissue regeneration and wound healing

Номер: US20180339013A1
Автор: Ira M. Herman, Tatiana DEMIDOVA-RICE
Принадлежит: TUFTS UNIVERSITY

Provided herein are methods and compositions for the treatment of wounds in a mammalian subject. Particularly, novel bioactive polypeptides are provided that promote tissue repair and regeneration, including the activation of/stimulation of wound healing and wound closure, stimulate keratinocyte and endothelial cell motility and/or proliferation.

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Номер записи: 96
08-12-2016 дата публикации

Method for Treating Adhesive Capsulitis

Номер: US20160354450A1
Автор: Badalamente Marie A., Wang Edward
Принадлежит:

The invention relates to the discovery that collagenase injections are effective in lyse the collagenous adhesions in the shoulder and treat the disorder, adhesive capsulitis. As such, the invention relates to methods of treating or preventing adhesive capsulitis, or frozen shoulder, in a patient in need of such treatment comprising injecting or otherwise delivering an effective amount of collagenase to the collagenous adhesions in the shoulder. The invention also relates to the use of collagenase in the manufacture of a medicament to treat adhesive capsulitis. 1. A method of treating or preventing adhesive capsulitis in a subject in need of such treatment comprising delivering an effective amount of collagenase to collagenous adhesions in the shoulder.2Clostridium histolyticum.. The method according to claim 1 , wherein the collagenase is derived from3. The method according to claim 2 , wherein the collagenase is injected in a dose comprising at least about 700 SRC units.4. The method according to claim 3 , wherein the collagenase is injected in a volume of less than 0.5 ml.5. The method according to claim 3 , wherein the collagenase comprises collagenase I and collagenase II.6. The method according to claim 4 , wherein the injection is delivered in a single injection between the interval of the deltoid and pectoral muscles.7. The method according to claim 1 , wherein the subject is a human patient.8. The method according to claim 7 , wherein the patient is characterized by an active forward elevation of only 90 degrees and an active external rotation of less than 50 degrees.9. The method according to claim 1 , wherein after one month of receiving at least one administration of collagenase claim 1 , the patient achieves an active external rotation of greater than 15 degrees claim 1 , as compared to baseline. This application is a continuation of U.S. application Ser. No. 14/572,104, filed Dec. 16, 2014, which is a continuation of U.S. application Ser. No. 13/688, ...

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Номер записи: 97
07-11-2019 дата публикации

FUSION PROTEINS OF COLLAGEN-BINDING DOMAIN AND PARATHYROID HORMONE

Номер: US20190338010A1
Автор: Gensure Robert C., Matsushita Osamu, Ponnapakkam Tulasi, Sakon Joshua
Принадлежит:

Fusion proteins containing active agonist or antagonist fragments of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) coupled to a collagen-binding domain are presented. The fusion proteins can be used to promote bone growth, to promote hair growth, to prevent cancer metastasis to bone, to promote immune reconstitution with a bone marrow stem cell transplant, to promote mobilization of bone marrow stem cells for collection for autologous stem cell transplant, and to treat renal osteodystrophy. Pharmaceutical agents comprising a collagen-binding polypeptide segment linked to a non-peptidyl PTH/PTHrP receptor agonist or antagonist are also presented. 160.-. (canceled)61. A composition comprising:a collagen-binding polypeptide segment covalently linked to a PTH/PTHrP receptor agonist;wherein the collagen-binding polypeptide segment is a bacterial collagen binding polypeptide segment, wherein the PTH/PTHrP receptor agonist comprises residues 1-14 of SEQ ID NO: 1, and wherein the collagen-binding polypeptide segment comprises a polypeptide fragment consisting of at least 10 consecutive amino acids of residues 38-158 of SEQ ID NO: 1.62. The composition of claim 61 , wherein the collagen-binding polypeptide segment and the PTH/PTHrP receptor agonist are chemically cross-linked to each other or are polypeptide portions of a fusion protein.63. The composition of claim 61 , wherein the composition has at least 50% greater activity than PTH(1-34) as measured by increased bone mineral density after eight weeks of weekly administration of the composition to a subject in need thereof at equal molar doses of the PTH.64. The composition of claim 61 , wherein the PTH/PTHrP receptor agonist is a polypeptide and the N-terminus of the collagen-binding polypeptide segment is linked directly or through a linker polypeptide segment to the C-terminus of the PTH/PTHrP receptor agonist polypeptide.65. The composition of claim 61 , wherein the PTH/PTHrP receptor ...

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Номер записи: 98
14-12-2017 дата публикации

Protease compositions for use in modifying semen

Номер: US20170354594A1
Автор: David S. Newburg, Marc L. Berger
Принадлежит: Individual

Provided herein are edible compositions for reducing semen viscosity and/or enhancing semen flavor, and methods of using and preparing such compositions.

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Номер записи: 99
29-10-2020 дата публикации

BACTERIAL STRAIN CLOSTRIDIUM HISTOLYTICUM AND ITS USE

Номер: US20200339941A1
Автор: BENESIK Martin, MOSA Marek
Принадлежит: MB Pharma s.r.o.

Bacterial strain was deposited in CCM (Czech Collection of Microorganisms at Masaryk University, Faculty of Science) under No. CCM 8656. This strain produces proteolytic enzymes including collagenase, elastinase, neutral proteases and clostripain under anaerobic conditions at a temperature from 25° C. to 45° C. The strain is used for the production of a mixture of two collagenases, col 1 and col 2, with molecular weight 116 kDa and 126 kDa, and possibly clostripain. The mixture of the above-mentioned collagenases and possibly clostripain obtained from the above-mentioned strain is used for the isolation of Langerhans islets. 1Clostridium histolyticum. A bacterial strain deposited under deposit number CCM 8656 , wherein said bacterial strain produces proteolytic enzymes including collagenase , elastinase , neutral proteases and clostripain under anaerobic conditions at a temperature from 25° C. to 45° C.2Clostridium histolyticum. A method for producing a mixture of two collagenases claim 1 , col 1 (SEQ ID NO: 1) and col 2 (SEQ ID NO: 2) claim 1 , with molecular weight of 116 kDa and 126 kDa claim 1 , the method comprising culturing the bacterial strain CCM 8656 of under anaerobic conditions at a temperature from 25° C. to 45° C.3Clostridium histolyticum. A method for producing a mixture of two collagenases claim 1 , col 1 (SEQ ID NO: 1) and col 2 (SEQ ID NO: 2) claim 1 , with molecular weight of 116 kDa and 126 kDa claim 1 , and clostripain claim 1 , the method comprising culturing the bacterial strain CCM 8656 of under anaerobic conditions at a temperature from 25° C. to 45° C.4Clostridium histolyticum. A method for isolating Langerhans islets claim 2 , the method comprising digesting pancreatic tissue with a mixture of two collagenases claim 2 , col 1 (SEQ ID NO: 1) and col 2 (SEQ ID NO: 2) claim 2 , with molecular weight of 116 kDa and 126 kDa claim 2 , produced by the bacterial strain CCM 8656 according to the method of claim 2 , to release the Langerhans islets ...

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Номер записи: 100