Charge conversional ternary polyplex

Disclosed is a polymer composite (polyplex) that contains nucleic acid, a cationic polymer, and an anionic polymer. The anionic polymer covers the surface of the composite comprising the cationic polymer and nucleic acid, has a negative charge at neutral pH, and can change so as to have a positive charge at mildly acidic pH.

FINE PARTICLES OF CRYSTALLINE POLYOL, AND METHOD OF PREPARING SAME

Fine particles of crystalline polyol are provided having a cationic polymer fixed on the crystal surfaces. These fine particles can stably carry an anionically charged compound on their surfaces. 1. A method of preparing fine particles of crystalline polyol having a cationic polymer fixed on the surface thereof , the comprising a step of freeze-drying an aqueous solution containing both a crystalline polyol and a cationic polymer.2. The preparation method according to claim 1 , wherein the crystalline polyol is in a crystalline state in the fine particles of crystalline polyol.3. The preparation method according to claim 1 , wherein the crystalline polyol is selected from the group consisting of mannitol claim 1 , trehalose claim 1 , xylitol claim 1 , sorbitol claim 1 , inositol claim 1 , glucose claim 1 , galactose claim 1 , sucrose claim 1 , mannose claim 1 , fructose claim 1 , ribose claim 1 , xylose claim 1 , dextrin and poly(ethylene glycol) having 10 to 2500 oxyethylene units claim 1 , and the cationic polymer is selected from the group consisting of polylysine claim 1 , polyarginine claim 1 , spermine claim 1 , spermidine claim 1 , chitosan claim 1 , polyethyleneimine claim 1 , poly(polyamine-modified aspartamide) claim 1 , poly(polyamine-modified glutamide) and copolymers containing blocks of polymer chains derived therefrom and blocks of polymer chains derived from poly(ethylene glycol).4. The preparation method according to claim 1 , wherein the aqueous solution containing both a crystalline polyol and a cationic polymer is a mixture of a crystalline polyol aqueous solution with a concentration of 0.1 to 10 w/v % and a cationic polymer aqueous solution with a concentration of 1 to 1000 μg/mL.5. The preparation method according to claim 1 , wherein resulting fine particles have an average particle diameter of 10 to 1000 nm and a positive ξ potential on surfaces thereof when measured in pure water.6. The preparation method according to claim 5 , wherein the ...

POLYION COMPLEX OF DOUBLE-STRANDED RIBONUCLEIC ACID

Provided are a delivery system that is useful in delivering a double-stranded ribonucleic acid that functions in gene silencing in glomeruli, particularly in mesangial cells and the like, to the tissue or cells, and the like. A polyion complex in the form of a non-polymeric micelle consisting of a double-stranded ribonucleic acid and a block copolymer represented by the formula (I) or (II) below, which are electrostatically bound together, wherein the polyion complex has an average particle diameter of less than 100 nm as measured by a dynamic light scattering measuring method: 2. The polyion complex according to claim 1 , wherein the double-stranded ribonucleic acid is an siRNA.3. The polyion complex according to claim 1 , which has an average particle diameter of less than 50 nm.4. The polyion complex according to claim 1 , which has an average particle diameter of 10 to less than 20 nm.5. A pharmaceutical composition comprising the polyion complex according to and a pharmaceutically acceptable carrier.6. The pharmaceutical composition according to claim 5 , which is to be delivered to a glomerulus or mesangial cell.7. The pharmaceutical composition according to claim 6 , which is to be used to treat or prevent renal diseases whose pathologic condition occurs mainly in mesangium.9. The kit according to claim 8 , which further comprises a container housing a double-stranded ribonucleic acid.10. The kit according to claim 8 , which further comprises an instruction sheet stating that the block copolymer and the double-stranded ribonucleic acid be mixed in a ratio of N/P=1.2 to 1.5 (N represents the total number of cations in the block copolymer; P represents the total number of phosphoester bonds or equivalent bonds in the double-stranded ribonucleic acid).11. The kit according to claim 8 , which is to be used for delivery to glomeruli or mesangial cells.12. A method for treating or preventing a renal disease comprising a step of administering the pharmaceutical ...

Short-chain cationic polyamino acid and use thereof

The present invention provides a cationic polyamino acid suitable for a carrier that can form a stable complex with a nucleic acid under a physiological condition and release the nucleic acid in cells suitably. The cationic polyamino acid can associate with a nucleic acid and includes a cationic amino acid residue having a cationic group in a side chain and a hydrophobic amino acid residue having a hydrophobic group in a side chain. The cationic polyamino acid includes 1 to 20 units of the cationic amino acid residue and is represented by the following formula (1). The meaning of each symbol in the formula is as shown in the description.

CATIONIC POLY (AMINO ACIDS) AND USES THEREOF

The present invention provides an efficient delivery system for a nucleic acid, more specifically, a cationic poly(amino acid) that has a side chain having a plurality of different amine functional groups in a moiety including a cationic group and that has a hydrophobic group introduced into part of the side chain, and a polyion complex (PIC) of the poly(amino acid) and an oligo- or polynucleotide.

Carrier for use in delivering drug, conjugate, composition comprising same, and method for administrating same

The present invention provides a vesicle, a conjugate, a composition comprising the vesicle or the conjugate, for use in delivering a drug to the brain, and a method for administering the same. The composition of the present invention is a composition for administration to a subject according to a dosing regimen, comprising a carrier for drug delivery, wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject, and the carrier is modified at the outer surface thereof with a GLUT1 ligand.

Unit structure-type pharmaceutical composition for nucleic acid delivery

A unit structure-type pharmaceutical composition includes a single nucleic acid, such as an antisense nucleic acid, electrostatically bound to a single block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. The negative charges of the nucleic acid are counterbalanced, at least substantially, by the positive charges of the cationic polyamino acid segment such that the pharmaceutical composition is electrically neutral or nearly electrically neutral. Further, the nucleic acid is covered with the hydrophilic polymer chain segment. The block copolymer thereby improves the blood retention capability of the nucleic acids.

CHARGE CONVERSIONAL TERNARY POLYPLEX

Disclosed is a polymer composite (polyplex) that contains nucleic acid, a cationic polymer, and an anionic polymer. The anionic polymer covers the surface of the composite comprising the cationic polymer and nucleic acid, has a negative charge at neutral pH, and can change so as to have a positive charge at mildly acidic pH.

SHORT-CHAIN CATIONIC POLYAMINO ACID AND USE THEREOF

The present invention provides a cationic polyamino acid suitable for a carrier that can form a stable complex with a nucleic acid under a physiological condition and release the nucleic acid in cells suitably. The cationic polyamino acid can associate with a nucleic acid and includes a cationic amino acid residue having a cationic group in a side chain and a hydrophobic amino acid residue having a hydrophobic group in a side chain. The cationic polyamino acid includes 1 to 20 units of the cationic amino acid residue and is represented by the following formula (1). The meaning of each symbol in the formula is as shown in the description.

Cationic poly (amino acids) and uses thereof

The present invention provides an efficient delivery system for a nucleic acid, more specifically, a cationic poly(amino acid) that has a side chain having a plurality of different amine functional groups in a moiety including a cationic group and that has a hydrophobic group introduced into part of the side chain, and a polyion complex (PIC) of the poly(amino acid) and an oligo- or polynucleotide.

CARRIER FOR USE IN DELIVERING DRUG, CONJUGATE, COMPOSITION COMPRISING SAME, AND METHOD FOR ADMINISTRATING SAME

The present invention provides a vesicle, a conjugate, a composition comprising the vesicle or the conjugate, for use in delivering a drug to the brain, and a method for administering the same. The composition of the present invention is a composition for administration to a subject according to a dosing regimen, comprising a carrier for drug delivery, wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject, and the carrier is modified at the outer surface thereof with a GLUT1 ligand. 12-. (canceled)3. A method for administering a drug to a subject , comprising:lowering blood glucose level in the subject; and subsequentlyadministering a drug to the subject whose blood glucose level has been lowered and increasing blood glucose level in the subject,wherein the drug is included in a carrier having an outer surface modified with a GLUT1 ligand.4. The method of claim 3 , wherein the carrier is a vesicle claim 3 , and 10 to 40% by mol of a polymer constituting the vesicle is modified with the GLUT1 ligand.5. The method of claim 3 , wherein the carrier is a vesicle claim 3 , and 40 to 100% by mol of a polymer constituting the vesicle is modified with the GLUT1 ligand.6. The method of claim 3 , wherein the carrier is a vesicle having a diameter of 400 nm or smaller.7. The method of claim 3 , wherein the GLUT1 ligand is glucose.8. The method of claim 3 , wherein the drug is at least one selected from the group consisting of a biologically active substance claim 3 , an antibody claim 3 , a nucleic acid claim 3 , a biocompatible fluorescent dye claim 3 , and a contrast medium.9. The method of claim 3 , wherein the carrier is a conjugate of one molecule of the GLUT1 ligand and one molecule of a polymer claim 3 , and the conjugate is capable of forming a vesicle such that the GLUT1 ligand is exposed on a surface of the vesicle.10. The method ...

Carrier for use in delivering drug, conjugate, composition comprising same, and method for administrating same

The present invention provides a vesicle, a conjugate, a composition comprising the vesicle or the conjugate, for use in delivering a drug to the brain, and a method for administering the same. The composition of the present invention is a composition for administration to a subject according to a dosing regimen, comprising a carrier for drug delivery, wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject, and the carrier is modified at the outer surface thereof with a GLUT1 ligand.

Polycationically charged polymer and the use of the same as a carrier for nucleic acid

Disclosed is a composition for the delivery of nucleic acid to target cells or tissues, which comprises a polycationically charged polymer as a carrier of nucleic acid. The polycationically charged polymer is a polymer which may comprise a charged polymer segment having a main chain based on poly(amino acid), polysaccharide, polyester, polyether, polyurethane or vinyl polymer and having, as a side chain, a group of formula NH(CH2)a(NH(CH2)2)eNH2 (wherein a and e independently denote an integer of 1 to 5) which is connected to the main chain either directly or via a linker. The disclosed composition has low toxicity, and has a high efficiency in introducing nucleic acid into cells.

Substance-encapsulating vesicle and process for producing the same

Provided is a method for easily and efficiently producing encapsulated substance vesicles wherein a substance is encapsulated in the cavity of vesicles obtained by polymer self-assembly. Empty vesicles that have membranes comprising a first polymer that is a block copolymer with uncharged hydrophilic segments and a first kind of charged segments and a second polymer with a second kind of charged segments that carry a charge that is the opposite of said first kind of charged segments as well as spaces that are enclosed by said membranes are mixed in an aqueous medium with the substance that is to be encapsulated in the spaces.

Antitumor drug delivery formulation

This invention provides an antitumor drug delivery formulation for treating a subject having a tumor more highly expressing a TUG1 gene than normal tissues or preventing the subject from tumor metastasis, comprising a polymeric micelle comprising a nucleic acid that suppresses high expression of the TUG1 gene as an active ingredient, wherein the polymeric micelle comprises a block copolymer having a cationic poly(amino acid) segment and a hydrophilic polymer chain segment and the nucleic acid, and wherein the nucleic acid is bound to a cationic group of the cationic poly(amino acid) segment to form a complex and/or the nucleic acid is incorporated in the micelle or attached into the micelle; and the polymeric micelle accumulates in the tumor.

AMPHIPHILIC POLY (AMINO ACID), BLOCK COPOLYER USING THE AMPHIPHILIC POLY (AMINO ACID), AND COMPLEX INCLUDING THE AMPHIPHILIC POLY (AMINO ACID) OR THE BLOCK COPOLYMER AND NUCLEIC ACID

The present invention provides an amphiphilic poly(amino acid) for nucleic acid delivery, which is represented by the following formula (1): where: R1 represents a hydroxy group, an oxybenzyl group, an —O—R1a group, or an —NH—R1b group, where R1a and R1b each independently represent an unsubstituted or substituted, linear or branched alkyl group having 1 to 12 carbon atoms; R2 represents a hydrogen atom, an unsubstituted or substituted, linear or branched alkyl group having 1 to 12 carbon atoms, or an unsubstituted or substituted, linear or branched alkylcarbonyl group having 1 to 24 carbon atoms; R3a, R3b, R4a, and R4b each independently represent a methylene group or an ethylene group; R5a and R5b each independently represent —O— or —NH—; R6a and R6b each independently represent an unsubstituted or substituted aliphatic hydrocarbon group having 7 to 12 carbon atoms that may contain an alicycle; R7a and R7b are each independently selected from groups identical to or different from each other in the group consisting of the following groups: —NH—(CH2)p1—[NH—(CH2)q1—]r1NH2 (i); —NH—(CH2)p2—N[—(CH2)q2—NH2]2 (ii); —NH—(CH2)p3—N{[—(CH2)q3—NH2][—(CH2)q4—NH—]r2H} (iii); and —NH—(CH2)p4—N{—(CH2)q5—N[—(CH2)q6—NH2]2}2 (iv), where p1 to p4, q1 to q6, and r1 and r2 each independently represent an integer of from 1 to 5; R8 represents a side chain of an amino acid selected from the group consisting of ornithine, lysine, homolysine, arginine, homoarginine, and histidine; m represents an integer of 9 or more; n represents an integer of from 0 to m; x represents an integer of from 2 to 300; y represents an integer of from 0 to x; and z represents an integer of from 0 to x, provided that a relationship of y+z≤x and a relationship of 11≤m+x≤400 are satisfied, and repeating units in the formula (1) may be randomly present.

Micelle composition for nucleic acid delivery using temperature-sensitive polymer and method for producing same

Provided are a micelle composition for nucleic acid delivery using a temperature-sensitive polymer, and a method for producing the micelle. For example, provided is a polyion complex comprising a temperature-sensitive copolymer and a nucleic acid, wherein the temperature-sensitive copolymer comprises a cationic block and a temperature-sensitive block, the cationic block optionally carrying a hydrophilic block linked thereto, and the polyion complex is obtained by mixing the temperature-sensitive copolymer with the nucleic acid under temperature conditions equal to or lower than the lower critical solution temperature (LCST) of the temperature-sensitive copolymer.

Polycationically Charged Polymer and the Use of the Same as a Carrier for Nucleic Acid

A composition for the delivery of nucleic acid to target cells or tissues, which comprises polycationically charged polymer as a carrier of nucleic acid is provided. Said polycationically charged polymer is a polymer which may comprise a charged polymer segment having a main chain based on poly(amino acid), polysaccharide, polyester, polyether, polyurethane or vinyl polymer and having, as a side chain, a group of formula —NH—(CH2)a—(NH(CH2)2)e—NH2 (wherein a and e independently denote an integer of 1 to 5) which is connected to said main chain either directly or via a linker. This composition is low-toxic, and has a high efficiency in introducing nucleic acid into cells.

COPOLYMER INCLUDING UNCHARGED HYDROPHILIC BLOCK AND CATIONIC POLYAMINO ACID BLOCK HAVING HYDROPHOBIC GROUP IN PART OF SIDE CHAINS, AND USE THEREOF

The present invention relates to a block copolymer containing an uncharged hydrophilic polymer chain block and a cationic polyamino acid chain block, wherein the hydrophilic polymer chain block is covalently bound to one end of the main chain of the polyamino acid chain block, and the hydrophobic group is covalently bound to the side chains of not less than 10% and not greater than 70% of amino acid repeating units in the polyamino acid chain block. This block copolymer forms a stable aggregate with siRNA, a small-molecule nucleic acid, under a physiological condition.

Polyion complex of double-stranded ribonucleic acid

Provided are a delivery system that is useful in delivering a double-stranded ribonucleic acid that functions in gene silencing in glomeruli, particularly in mesangial cells and the like, to the tissue or cells, and the like. A polyion complex in the form of a non-polymeric micelle consisting of a double-stranded ribonucleic acid and a block copolymer represented by the formula (I) or (II) below, which are electrostatically bound together, wherein the polyion complex has an average particle diameter of less than 100 nm as measured by a dynamic light scattering measuring method: wherein each symbol is as defined in the specification.

Copolymer including uncharged hydrophilic block and cationic polyamino acid block having hydrophobic group in part of side chains, and use thereof

The present invention relates to a block copolymer containing an uncharged hydrophilic polymer chain block and a cationic polyamino acid chain block, wherein the hydrophilic polymer chain block is covalently bound to one end of the main chain of the polyamino acid chain block, and the hydrophobic group is covalently bound to the side chains of not less than 10% and not greater than 70% of amino acid repeating units in the polyamino acid chain block. This block copolymer forms a stable aggregate with siRNA, a small-molecule nucleic acid, under a physiological condition.

Substance-encapsulating vesicle and process for producing the same

Provided is a method for easily and efficiently producing encapsulated substance vesicles wherein a substance is encapsulated in the cavity of vesicles obtained by polymer self-assembly. Empty vesicles that have membranes comprising a first polymer that is a block copolymer with uncharged hydrophilic segments and a first kind of charged segments and a second polymer with a second kind of charged segments that carry a charge that is the opposite of said first kind of charged segments as well as spaces that are enclosed by said membranes are mixed in an aqueous medium with the substance that is to be encapsulated in the spaces.

Anionic polymer, polyion complex and ternary polymer composite using anionic polymer, and pharmaceutical composition

There are provided an anionic polymer, a polyion complex, and a ternary polymer composite, each of which is stable in a biological environment and is capable of realizing small RNA delivery without causing any undesired immune response. An anionic polymer according to an embodiment of the invention includes: a main chain which includes repeating units having carboxyl groups; and a side chain which is linked with part of the carboxyl groups in the main chain and is represented by the following formula: -A-B—X where: A represents a residue having one or more aminoethyl bonds; B represents an in vivo cleavable bond; and X represents a small RNA. A polyion complex according to an embodiment of the invention includes the anionic polymer as described above and a cationic polymer. A ternary polymer composite according to an embodiment of the invention includes the polyion complex as described above and a charge conversional polymer.

Particle composition and pharmaceutical composition using particle composition

A composition of matter for use in encapsulating a drug is expressed by formula (1) or formula (2): wherein R1 and R2 are each independently a hydrogen atom or a substituted or unsubstituted, linear or branched alkyl group having 1 to 12 carbon atoms; A is a hydrophilic polymer chain; L1 and L3 are each a linking group; B is a cation-containing group; R3 is a side chain of an amino acid; z is an integer of 5 to 500; x is an integer of 40% or more of z; y is 0 or a positive integer; z-x-y is 0 or a positive integer; p is an integer of 1 to 10; and q is an integer of 1 to 10.

Substance-encapsulating vesicle and process for producing the same

Provided is a method for easily and efficiently producing encapsulated substance vesicles wherein a substance is encapsulated in the cavity of vesicles obtained by polymer self-assembly. Empty vesicles that have membranes comprising a first polymer that is a block copolymer with uncharged hydrophilic segments and a first kind of charged segments and a second polymer with a second kind of charged segments that carry a charge that is the opposite of said first kind of charged segments as well as spaces that are enclosed by said membranes are mixed in an aqueous medium with the substance that is to be encapsulated in the spaces. 1. A process of producing a substance-encapsulating vesicle , which encapsulates a substance in a cavity thereof , comprising:providing a vacant vesicle having a membrane containing a first polymer, which is a block copolymer having an uncharged hydrophilic segment and a first charged segment, and a second polymer, which has a second charged segment charged oppositely to the first charged segment, said membrane defining a cavity surrounded thereby; andmixing the vacant vesicle and the substance in an aqueous medium.2. A process according to claim 1 , wherein the mixing is carried out by a process selected from the group consisting of agitating claim 1 , shaking claim 1 , and impacting.3. A process according to claim 1 , wherein the membrane of the vacant vesicle has a trilaminar structure comprising an outer layer claim 1 , an intermediate layer claim 1 , and an inner layer.4. A process according to claim 1 , wherein the substance is selected from the group consisting of biomolecules claim 1 , organic compounds and inorganic substances.5. A process according to claim 1 , wherein the first polymer is a block copolymer containing an uncharged hydrophilic segment and an anionic segment claim 1 , and the second polymer is a block copolymer containing an uncharged hydrophilic segment and a cationic segment and/or a polymer containing a cationic ...

PARTICLE COMPOSITION AND PHARMACEUTICAL COMPOSITION USING PARTICLE COMPOSITION

A composition of matter for use in encapsulating a drug is expressed by formula (1) or formula (2): wherein R 1 and R 2 are each independently a hydrogen atom or a substituted or unsubstituted, linear or branched alkyl group having 1 to 12 carbon atoms; A is a hydrophilic polymer chain; L 1 and L 3 are each a linking group; B is a cation-containing group; R 3 is a side chain of an amino acid; z is an integer of 5 to 500; x is an integer of 40% or more of z; y is 0 or a positive integer; z-x-y is 0 or a positive integer; p is an integer of 1 to 10; and q is an integer of 1 to 10.

SUBSTANCE-ENCAPSULATING VESICLE AND PROCESS FOR PRODUCING THE SAME

Provided is a method for easily and efficiently producing encapsulated substance vesicles wherein a substance is encapsulated in the cavity of vesicles obtained by polymer self-assembly. Empty vesicles that have membranes comprising a first polymer that is a block copolymer with uncharged hydrophilic segments and a first kind of charged segments and a second polymer with a second kind of charged segments that carry a charge that is the opposite of said first kind of charged segments as well as spaces that are enclosed by said membranes are mixed in an aqueous medium with the substance that is to be encapsulated in the spaces.

Unit structure-type pharmaceutical composition for nucleic acid delivery

A unit structure-type pharmaceutical composition includes at least one nucleic acid, such as siRNA, electrostatically bound to at least one block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. The negative charge(s) of the nucleic acid are counterbalanced, at least substantially, by the positive charge(s) of the cationic polyamino acid segment such that the pharmaceutical composition is electrically neutral or nearly electrically neutral. Further, the nucleic acid is covered with the hydrophilic polymer chain segment(s). The at least one block copolymer thereby improves the blood retention capability of the nucleic acid(s).

Nucleic acid-loaded unit polyion complex

A unit-type polyion complex for use in delivering nucleic acid to a target site in a patient includes one or more molecules of a block copolymer having a poly(ethylene glycol) segment and a cationic poly(amino acid) segment and one or more molecules of a nucleic acid. A total quantity of positive charges derived from side chains of the cationic poly(amino acid) segment of the block copolymer in the unit-type polyion complex is not offset by a total quantity of negative charges derived from the nucleic acid. Furthermore, the nucleic acid has a strand length of 10-50 bases, the molecular weight of the poly(ethylene glycol) segment is 40×103or more, and the block copolymer has a binding constant (Ka) for the nucleic acid of 3.0×105or more.

ANIONIC POLYMER, POLYION COMPLEX AND TERNARY POLYMER COMPOSITE USING ANIONIC POLYMER, AND PHARMACEUTICAL COMPOSITION

There are provided an anionic polymer, a polyion complex, and a ternary polymer composite, each of which is stable in a biological environment and is capable of realizing small RNA delivery without causing any undesired immune response. An anionic polymer according to an embodiment of the invention includes: a main chain which includes repeating units having carboxyl groups; and a side chain which is linked with part of the carboxyl groups in the main chain and is represented by the following formula: 2. The anionic polymer of claim 1 , wherein the main chain comprises at least one selected from the group consisting of a polyamino acid having a carboxyl group claim 1 , a polyvinyl having a carboxyl group claim 1 , a polyester having a carboxyl group claim 1 , a polysaccharide having a carboxyl group claim 1 , and a dendrimer (cascade polymer) having a carboxyl group claim 1 , thereof.3. The anionic polymer of claim 1 , wherein the in vivo cleavable bond is a disulfide bond claim 1 , an acetal bond claim 1 , or a hydrazone bond.5. The anionic polymer of claim 4 , wherein A represents —NH—(CH)— and Q represents —OH.6. The anionic polymer of claim 4 , wherein l represents is an integer of 2 or more.7. A polyion complex claim 4 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the anionic polymer of ; and'}a cationic polymer selected from the group consisting of polyethylene imine, polyarginine, polylysine, poly-[2-{(2-aminoethyl)amino}-ethyl-aspartamide] (pAsp(DET)), a block co-polymer of polyethylene glycol and polyarginine, a block co-polymer of polyethylene glycol and polylysine, and a block co-polymer of polyethylene glycol and poly-[2-{(2-aminoethyl)amino}-ethyl-aspartamide] (PEG-pAsp(DET)).10. The ternary polymer composite of claim 8 , wherein the amine compound residue having a primary amine is —NH—(CH)—NHor —NH—(CH)—NH—(CH)—NH.12. A pharmaceutical composition claim 8 , comprising:{'claim-ref': {'@idref': 'CLM-00007', 'claim 7'}, 'the polyion ...

Fine particles of crystalline polyol, and method of preparing same

Fine particles of crystalline polyol are provided having a cationic polymer fixed on the crystal surfaces. These fine particles can stably carry an anionically charged compound on their surfaces.

UNIT STRUCTURE-TYPE PHARMACEUTICAL COMPOSITION FOR NUCLEIC ACID DELIVERY

A unit structure-type pharmaceutical composition includes a single nucleic acid, such as an antisense nucleic acid, electrostatically bound to a single block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. The negative charges of the nucleic acid are counterbalanced, at least substantially, by the positive charges of the cationic polyamino acid segment such that the pharmaceutical composition is electrically neutral or nearly electrically neutral. Further, the nucleic acid is covered with the hydrophilic polymer chain segment. The block copolymer thereby improves the blood retention capability of the nucleic acids. 19.-. (canceled)10. A unit structure , consisting of:a single nucleic acid having a length of 10 to 30 bases, anda single block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment,wherein:(i) a difference between a total of positive charges derived from cationic groups of the cationic polyamino acid segment and a total of negative charges derived from the nucleic acid in the unit structure falls within a range of ±10% of the total of the negative charges derived from the nucleic acid,(ii) the hydrophilic polymer chain segment comprises polyethylene glycol,(iii) the polyethylene glycol has a radius of inertia (Rg) equal to or longer than the length of the nucleic acid, and(iv) the cationic polyamino acid segment is bound to the nucleic acid via electrostatic bonds.11. The unit structure according to claim 10 , wherein:the hydrophilic polymer chain segment comprises a 2-arm branched polyethylene glycol, andeach of the arms of the 2-arm branched polyethylene glycol has a radius of inertia (Rg) equal to or longer than the length of the nucleic acid.12. The unit structure according to claim 10 , wherein all cationic amino acids in the cationic polyamino acid segment have only one cationic group in each side chain.13. The unit structure according to claim 10 , wherein the ...

Unit structure-type pharmaceutical composition for nucleic acid delivery

A unit structure-type pharmaceutical composition includes at least one nucleic acid, such as siRNA, electrostatically bound to at least one block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. The negative charge(s) of the nucleic acid are counterbalanced, at least substantially, by the positive charge(s) of the cationic polyamino acid segment such that the pharmaceutical composition is electrically neutral or nearly electrically neutral. Further, the nucleic acid is covered with the hydrophilic polymer chain segment(s). The at least one block copolymer thereby improves the blood retention capability of the nucleic acid(s).

CHARGE CONVERSIONAL TERNARY POLYPLEX

Disclosed is a polymer composite (polyplex) that contains nucleic acid, a cationic polymer, and an anionic polymer. The anionic polymer covers the surface of the composite comprising the cationic polymer and nucleic acid, has a negative charge at neutral pH, and can change so as to have a positive charge at mildly acidic pH. 2. The anionic polymer according to claim 1 , wherein the residue derived from an amine compound having a primary amine is a group of General Formula (11):{'br': None, 'sub': 2', 'r, 'sup': '11', '—NH—(CH)—X\u2003\u2003(11)'}{'sup': '11', 'claim-text': {'br': None, 'sub': 2', 's1', 't1, 'sup': '12', '—[NH—(CH)]—X\u2003\u2003(12)'}, 'wherein Xrepresents an amine compound residue derived from primary, secondary or tertiary amine compound or quaternary ammonium salt, and r represents an integer of 0-5, or a group of General Formula (12){'sup': 12', '11, 'sub': 2', '51, 'wherein Xis synonymous with X, and s1 and t1, independently from each other and independently between [NH—(CH)] units, represent integers of 1-5 and 2-5, respectively.'}3. The anionic polymer according to claim 1 , wherein the residue derived from an amine compound having a primary amine is —NH—NHor —NH—(CH)—NH—(CH)—NH.5. A polymer complex comprising a nucleic acid claim 1 , a cationic polymer and the anionic polymer according to any one of .6. (canceled)8. A device for delivering a nucleic acid into a cell claim 5 , comprising the polymer complex according to .9. A kit for delivering a nucleic acid into a cell claim 5 , comprising the polymer complex according to .10. A polymer complex comprising a nucleic acid claim 2 , a cationic polymer and the anionic polymer according to .11. A polymer complex comprising a nucleic acid claim 3 , a cationic polymer and the anionic polymer according to .12. A polymer complex comprising a nucleic acid claim 4 , a cationic polymer and the anionic polymer according to .16. A device for delivering a nucleic acid into a cell claim 10 , comprising the ...

UNIT STRUCTURE-TYPE PHARMACEUTICAL COMPOSITION FOR NUCLEIC ACID DELIVERY

A unit structure consists of a single nucleic acid having a length of 10 to 30 bases, and a single block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment. In this unit structure: (i) a difference between a total of positive charges derived from cationic groups of the cationic polyamino acid segment and a total of negative charges derived from the nucleic acid in the unit structure falls within a range of ±10% of the total of the negative charges derived from the nucleic acid, (ii) the hydrophilic polymer chain segment comprises polyethylene glycol, (iii) the polyethylene glycol has a radius of inertia (Rg) equal to or longer than the length of the nucleic acid, and (iv) the cationic polyamino acid segment is bound to the nucleic acid via electrostatic bonds. 1. A unit structure , consisting of:a single nucleic acid having a length of 10 to 30 bases, anda single block copolymer having a cationic polyamino acid segment and a hydrophilic polymer chain segment,wherein:(i) a difference between a total of positive charges derived from cationic groups of the cationic polyamino acid segment and a total of negative charges derived from the nucleic acid in the unit structure falls within a range of ±10% of the total of the negative charges derived from the nucleic acid,(ii) the hydrophilic polymer chain segment comprises polyethylene glycol,(iii) the polyethylene glycol has a radius of inertia (Rg) equal to or longer than the length of the nucleic acid, and(iv) the cationic polyamino acid segment is bound to the nucleic acid via electrostatic bonds.2. The unit structure according to claim 1 , wherein:the hydrophilic polymer chain segment comprises a 2-arm branched polyethylene glycol, andeach of the arms of the 2-arm branched polyethylene glycol has a radius of inertia (Rg) equal to or longer than the length of the nucleic acid.3. The unit structure according to claim 1 , wherein all cationic amino acids in the cationic polyamino acid ...

Nucleic acid-loaded unit polyion complex

A unit-type polyion complex for use in delivering nucleic acid to a target site in a patient includes one or more molecules of a block copolymer having a poly(ethylene glycol) segment and a cationic poly(amino acid) segment and one or more molecules of a nucleic acid. A total quantity of positive charges derived from side chains of the cationic poly(amino acid) segment of the block copolymer in the unit-type polyion complex is not offset by a total quantity of negative charges derived from the nucleic acid. Furthermore, the nucleic acid has a strand length of 10-50 bases, the molecular weight of the poly(ethylene glycol) segment is 40×10 3 or more, and the block copolymer has a binding constant (Ka) for the nucleic acid of 3.0×10 5 or more.

CARRIER FOR USE IN DELIVERING DRUG, CONJUGATE, COMPOSITION COMPRISING SAME, AND METHOD FOR ADMINISTRATING SAME

The present invention provides a vesicle, a conjugate, a composition comprising the vesicle or the conjugate, for use in delivering a drug to the brain, and a method for administering the same. The composition of the present invention is a composition for administration to a subject according to a dosing regimen, comprising a carrier for drug delivery, wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject, and the carrier is modified at the outer surface thereof with a GLUT1 ligand. 1. A composition for administration to a subject according to a dosing regimen , the composition comprising a carrier for drug delivery , wherein:the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject; andthe carrier is modified at an outer surface thereof with a GLUT1 ligand.2. A composition for administration to a subject according to a dosing regimen comprising a conjugate of a drug and a GLUT1 ligand ,wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject.3. The composition according to claim 1 , wherein the composition is adapted to deliver a drug to the brain.4. The composition according to claim 1 , wherein the composition is adapted to function by permeating a drug across the blood-brain barrier.5. The composition according to claim 1 , wherein the composition is adapted to function by permeating a drug across the blood-nerve barrier claim 1 , the blood-retina barrier claim 1 , or the blood-cerebrospinal fluid barrier.6. The composition according to claim 1 , wherein the composition is adapted to function by delivering a drug to a cerebrovascular endothelial cell.7. The ...

Micelle composition for nucleic acid delivery using temperature-sensitive polymer and method for producing same

Provided are a micelle composition for nucleic acid delivery using a temperature-sensitive polymer, and a method for producing the micelle. For example, provided is a polyion complex comprising a temperature-sensitive copolymer and a nucleic acid, wherein the temperature-sensitive copolymer comprises a cationic block and a temperature-sensitive block, the cationic block optionally carrying a hydrophilic block linked thereto, and the polyion complex is obtained by mixing the temperature-sensitive copolymer with the nucleic acid under temperature conditions equal to or lower than the lower critical solution temperature (LCST) of the temperature-sensitive copolymer.

Antitumor drug delivery formulation

This invention provides an antitumor drug delivery formulation for treating a subject having a tumor more highly expressing a TUG1 gene than normal tissues or preventing the subject from tumor metastasis, comprising a polymeric micelle comprising a nucleic acid that suppresses high expression of the TUG1 gene as an active ingredient, wherein the polymeric micelle comprises a block copolymer having a cationic poly(amino acid) segment and a hydrophilic polymer chain segment and the nucleic acid, and wherein the nucleic acid is bound to a cationic group of the cationic poly(amino acid) segment to form a complex and/or the nucleic acid is incorporated in the micelle or attached into the micelle; and the polymeric micelle accumulates in the tumor.

ポリカチオン荷電性ポリマー及び核酸のキャリヤーとしての使用

ポリカチオン荷電性ポリマーを核酸のキャリヤーとして含んでなる標的細胞または組織への核酸デリバリー用組成物が提供される。該ポリカチオン荷電性ポリマーは、ポリ(アミノ酸)、多糖、ポリエステル、ポリエーテル、ポリウレタンまたはビニルポリマーをベースとする主鎖を有し、かつ、側鎖として、当該主鎖に結合または連結基を介して結合した式-NH-(CH2)a-(NH(CH2)2)e-NH2で表される基(ここで、a及びeはそれぞれ独立して1～5の整数ある)を含む荷電性ポリマーセグメントを含むことのできるポリマーである。かような組成物は、低毒性であり、細胞に対する高い核酸導入効率を有する。

Substance-encapsulating vesicle and process for producing the same

Provided is a method for easily and efficiently producing encapsulated substance vesicles wherein a substance is encapsulated in the cavity of vesicles obtained by polymer self-assembly. Empty vesicles that have membranes comprising a first polymer that is a block copolymer with uncharged hydrophilic segments and a first kind of charged segments and a second polymer with a second kind of charged segments that carry a charge that is the opposite of said first kind of charged segments as well as spaces that are enclosed by said membranes are mixed in an aqueous medium with the substance that is to be encapsulated in the spaces.

Substance-encapsulating vesicle and process for producing the same

Provided is a method for easily and efficiently producing encapsulated substance vesicles wherein a substance is encapsulated in the cavity of vesicles obtained by polymer self-assembly. Empty vesicles that have membranes comprising a first polymer that is a block copolymer with uncharged hydrophilic segments and a first kind of charged segments and a second polymer with a second kind of charged segments that carry a charge that is the opposite of said first kind of charged segments as well as spaces that are enclosed by said membranes are mixed in an aqueous medium with the substance that is to be encapsulated in the spaces.

Vesicles with encapsulated substance and production method therefor

Polycation chargeable polymer and use as carrier of nucleic acid

Cationic poly-amino acids and uses thereof

Particle composition and pharmaceutical composition using particle composition

The present invention provides a block copolymer applicable as a drug carrier capable of forming a stable complex with a nucleic acid and releasing the nucleic acid in cells. The block copolymer is represented by the following formula (1) or (2) where: R 1 and R 2 each independently represent a hydrogen atom or a linear or branched alkyl group having 1 to 12 carbon atoms which may have a substituent; A represents a hydrophilic polymer chain; L 1 and L 3 each represent a linking group; B represents a cation-containing group; R 3 represents a side chain of any appropriate amino acid; z represents an integer of 5 to 500; x represents an integer of 40% or more of z; y represents an integer and may represent 0; z-x-y represents an integer and may represent 0; p represents an integer of 1 to 10; and q represents an integer of 1 to 10.

Vesicles with encapsulated substance and production method therefor

Associative polymer material

【課題】高分子の溶液の濃度・溶媒を変えずに、所望の低浸透圧を実現する、生体適合性の新規高分子材料の提供。【解決手段】複数のポリマーユニットからなる高分子材料であって、溶媒を含有し、前記ポリマーユニットが、側鎖又は末端に１以上のボロン酸含有基を有する第１のポリマーユニットと、側鎖又は末端に１以上のポリオール基を有する第２のポリマーユニットを含み、前記高分子材料中のポリマー含有量が、前記ポリマーユニットの重なり合い濃度の２倍以下である、該高分子材料。【選択図】なし

Carrier for use in delivering drug, conjugate, composition comprising same, and method for administrating same

The present invention provides a vesicle for delivering a drug to the brain, a conjugate, a composition containing same, and a method for administering same. A composition for administration to a subject according to a dosing regimen, the composition containing a carrier for drug delivery, wherein the dosing regimen includes the administration of the composition to a subject who has been made to fast or in whom hypoglycemia has been induced and the induction of a rise in blood sugar levels in the subject, and the outer surface of the carrier in the composition is modified by a GLUT1 ligand.

Polymer having halogen-containing segment and pharmaceutical composition using same

The present invention provides a polymer represented by the following formula (I): wherein each symbol is as described in the specification, which is useful as a drug carrier in effectively delivering a drug to a target site.

核酸デリバリー用ユニット構造型医薬組成物

【課題】カチオン性ポリマー型キャリアにおける核酸の血中滞留性能を向上性の提供。 【解決手段】カチオン性ポリアミノ酸セグメントと親水性ポリマー鎖セグメントとを有する１つのブロックコポリマーと、１つの核酸と、からなり、該カチオン性ポリアミノ酸セグメントの正電荷と該核酸の負電荷とが相殺されて電気的に中性であり、該核酸が該親水性ポリマー鎖セグメントに覆われている、ユニット構造型医薬組成物であって、該核酸の鎖長が、１０〜３０塩基であり、該ブロックコポリマーが、カチオン性ポリアミノ酸セグメントと、該カチオン性ポリアミノ酸セグメントの片端に配置された該親水性ポリマー鎖セグメントとしてのポリ（エチレングリコール）鎖とを有し、該ポリ（エチレングリコール）鎖が、該核酸の長さ以上の慣性半径を有する、ユニット構造型医薬組成物。 【選択図】なし

Antitumor drug delivery formulation

Substance-encapsulating vesicle and process for producing the same

Formulering til administration af antitumorlægemiddel

Polyion complex of double-stranded ribonucleic acid

Short-chain cationic polyamino acid and use thereof

Polymer having halogen-containing segment and pharmaceutical composition using same

A polymer represented by the following formula (I): wherein each symbol is as described in the specification, is useful as a drug carrier in effectively delivering a drug to a target site.

複素環式ボロン酸誘導体

【課題】腫瘍細胞に対する結合性及び特異性の高い複素環式ボロン酸化合物を提供する。【解決手段】次式Ｉ：TIFF2023100685000013.tif59170（式中、Ｒ１は水素原子又は窒素原子を表し、Ｒ２は、単結合、又は－Ｃ（Ｏ）－、－Ｃ（Ｏ）Ｏ－、－Ｏ－、－ＣＯＮＨ－若しくは－ＮＨＣＯＯ－で示される基を表し、Ｒ３は、水素原子、置換基を有していてもよい炭化水素基、又は置換基を有していてもよい複素環式官能基を表す。）で示される、複素環式ボロン酸誘導体。【選択図】なし

遺伝子導入解析キット

【課題】長期間培養可能な細胞スフェロイドアレイを利用した遺伝子発現を検査するキットの提供 【解決手段】パタン化した基板上に内皮細胞のような第一の細胞を培養し、その上に肝臓のような第２の細胞をスフェロイド上に形成せしめ、長期培養を可能にした細胞スフェロイドアレイへ遺伝子を導入し、長期的に発現解析できることを可能にした。 【選択図】なし

Micelle composition for nucleic acid delivery using temperature-sensitive polymer and method for producing same

Amphiphilic poly(amino acid), block copolymer using the amphiphilic poly(amino acid), and complex including the amphiphilic poly(amino acid) or the block copolymer and nucleic acid

The present invention provides an amphiphilic poly(amino acid) for nucleic acid delivery, which is represented by the following formula (1): where: R 1 represents a hydroxy group, an oxybenzyl group, an -O-R 1a group, or an -NH-R 1b group, where R 1a and R 1b each independently represent an unsubstituted or substituted, linear or branched alkyl group having 1 to 12 carbon atoms; R 2 represents a hydrogen atom, an unsubstituted or substituted, linear or branched alkyl group having 1 to 12 carbon atoms, or an unsubstituted or substituted, linear or branched alkylcarbonyl group having 1 to 24 carbon atoms; R 3a , R 3b , R 4a , and R 4b each independently represent a methylene group or an ethylene group; R 5a and R 5b each independently represent -O- or -NH-; R 6a and R 6b each independently represent an unsubstituted or substituted aliphatic hydrocarbon group having 7 to 12 carbon atoms that may contain an alicycle; R 7a and R 7b are each independently selected from groups identical to or different from each other in the group consisting of the following groups: -NH-(CH 2 ) p1 -[NH-(CH 2 ) q1 -] r1 NH 2 (i); -NH-(CH 2 ) p2 -N[-(CH 2 ) q2 -NH 2 ] 2 (ii); -NH-(CH 2 ) p3 -N{[-(CH 2 ) q3 -NH 2 ][-(CH 2 ) q4 -NH-] r2 H} (iii); and -NH-(CH 2 ) p4 -N{-(CH 2 ) q5 -N[-(CH 2 ) q6 -NH 2 ] 2 } 2 (iv), where p1 to p4, q1 to q6, and r1 and r2 each independently represent an integer of from 1 to 5; R 8 represents a side chain of an amino acid selected from the group consisting of ornithine, lysine, homolysine, arginine, homoarginine, and histidine; m represents an integer of 9 or more; n represents an integer of from 0 to m; x represents an integer of from 2 to 300; y represents an integer of from 0 to x; and z represents an integer of from 0 to x, provided that a relationship of y+z≦x and a relationship of 11≦m+x≦400 are satisfied, and repeating units in the formula (1) may be randomly present.

Amphiphilic poly(amino acid), block copolymer using the amphiphilic poly(amino acid), and complex including the amphiphilic poly(amino acid) or the block copolymer and nucleic acid

核酸とカチオン性ポリマーとのポリイオンコンプレックスであって、正の表面電位を有し、核酸を脳組織に送達することができるポリイオンコンプレックス

【課題】核酸を脳組織に送達することができるポリイオンコンプレックス、および該ポリイオンコンプレックスを含む組成物提供する。 【解決手段】（ｉ）非電荷親水性ポリマーブロックとカチオン性アミノ酸を含むポリマーブロックを含むブロックコポリマーと、（ｉｉ）アニオン性ポリマーである一本鎖核酸と、を含むポリイオンコンプレックスであって、正の表面電位を有し、該核酸を細胞外から細胞質に送達することができるポリイオンコンプレックス、および、対象の鼻粘膜から経鼻投与し、対象の三叉神経または嗅球に核酸を送達することに用いる、該ポリイオンコンプレックスを含む組成物を提供する。 【選択図】なし

Temperature-responsive drug/polymer compound and application of compound to drug delivery

A drug-polymer conjugate having thermoresponsiveness includes at least one drug conjugated to at least one end portion of at least one thermoresponsive polymer segment having a lower critical solution temperature. The drug-polymer conjugate is capable of forming a micellular aggregate in an aqueous medium at temperatures equal to or above the lower critical solution temperature. The drug-polymer conjugate or the micellular aggregate thereof may be administered to and absorbed in the lungs.

Formulación de administración de fármaco antitumoral

La presente invención proporciona una formulación de administración de fármaco antitumoral para tratar sujetos que tienen un tumor con una alta expresión del gen TUG1 en comparación con el tejido normal o para prevenir metástasis tumorales en el mismo. La formulación de administración de fármacos se caracteriza por incluir, como componente activo, una micela polimérica que incluye un ácido nucleico que suprime la alta expresión del gen TUG1, y porque: la micela polimérica incluye dicho ácido nucleico y un copolímero de bloque que tiene un poliamino catiónico. segmento ácido y un segmento de cadena polimérica hidrófila; el ácido nucleico se une con el grupo catiónico del segmento de poliaminoácido catiónico para formar un complejo, y/o el ácido nucleico está encerrado o adherido al interior de la micela; y la micela polimérica se acumula en el tumor. (Traducción automática con Google Translate, sin valor legal)

Fine particles of crystalline polyol and method of preparing same