Sustained-release pharmaceutical compositions
AssigneeYissum Research Development Company of the Hebrew University of Jerusalem
InventorsMichael Friedman, Doron Steinberg, Aubrey Soskolne
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Abstract
The present invention pertains to biodegradable sustained-release composins capable of achieving the sustained release of a pharmaceutical or other agent. The compositions can be formed into implant devices which may be used to treat a wide variety of diseases and conditions. The implants are especially useful in treating diseases such as periodontal disease which require prolonged drug release.
Claims42
A liquid precursor composition for the preparation of a biodegradable sustained-release composition for the administration of an active agent, wherein said sustained-release composition is formed by solidification of said liquid precursor composition, said liquid precursor composition comprising:
- (1) a plasticizing agent, wherein said plasticizing agent is selected from the group consisting of a phthalate ester, a phosphate ester, a glycol derivative, a hydrocarbon, an oil, and a fatty acid;
- (2) said active agent, wherein said active agent is present in an amount sufficient to impart a desired therapeutic, agricultural, or catalytic property to said sustained-release composition;
- (3) a cross-linking agent, wherein said cross-linking agent is selected from the group consisting of aldehydes, alcohols, aluminum, chromium, titanium, zirconium, an acyl chloride, bis-diazobenzidine, phenol-2,4-disulfonyl chloride, 1,5-difluoro-2,4-dinitrobenzene, urea, 3,6-bis(mercurimethyl)-dioxane urea, dimethyl adipimidate and N,N'-ethylene-bis-iodacetamide;
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- (4) a water-soluble protein which is capable of being cross-linked into a water-insoluble, biodegradable polymeric matrix, wherein said water-soluble protein is present at a concentration sufficient to provide said sustained-release composition with structural stability after being cross-linked, but not at so great a concentration as to render said sustained-release composition (i) incapable of biodegradation or (ii) incapable of permitting the release of said active agent.
A biodegradable sustained-release composition for the administration of an active agent, wherein said sustained-release composition comprises:
- (1) a plasticizing agent, wherein said plasticizing agent is selected from the group consisting of a phthalate ester, a phosphate ester, a glycol derivative, a hydrocarbon, an oil, and a fatty acid;
- (2) said active agent, wherein said active agent is present in an amount sufficient to impart a desired therapeutic, agricultural, or catalytic property to said sustained-release composition;
- (3) a cross-linking agent, wherein said cross-linking agent is selected from the group consisting of aldehydes, alcohols, aluminum, chromium, titanium, zirconium, an acyl chloride, bis-diazobenzidine, phenol-2,4-disulfonyl chloride, 1,5-difluoro-2,4-dinitrobenzene, urea, 3,6-bis(mercurimethyl)-dioxane urea, dimethyl adipimidate and N,N'-ethylene-bis-iodacetamide;
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- (4) a biodegradable polymeric matrix comprising a cross-linked, water-insoluble protein, wherein said matrix formed upon the cross-linking of a water-soluble protein, and wherein said cross-linked, water-insoluble, protein is present at a concentration sufficient to provide said sustained-release composition with structural stability after being cross-linked, but not at so great a concentration as to render said sustained-release composition (i) incapable of biodegradation or (ii) incapable of permitting the release of said active agent.
A method for the administration of an active agent, wherein said method comprises the administration of a liquid precursor composition, wherein said liquid precursor composition solidifies to form a biodegradable sustained-release composition after said administration, said liquid precursor composition comprising:
- (1) a plasticizing agent, wherein said plasticizing agent is selected from the group consisting of a phthalate ester, a phosphate ester, a glycol derivative, a hydrocarbon, an oil, and a fatty acid;
- (2) said active agent, wherein said active agent is present in an amount sufficient to impart a desired therapeutic, agricultural, or catalytic property to said sustained-release composition;
- (3) a cross-linking agent, wherein said cross-linking agent is selected from the group consisting of aldehydes, alcohols, aluminum, chromium, titanium, zirconium, an acyl chloride, bis-diazobenzidine, phenol-2,4-disulfonyl chloride, 1,5-difluoro-2,4-dinitrobenzene, urea, 3,6-bis(mercurimethyl)-dioxane urea, dimethyl adipimidate and N,N'-ethylene-bis-iodacetamide;
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- (4) a water-soluble protein which is capable of being cross-linked into a water-insoluble, biodegradable polymeric matrix, wherein said water-soluble protein is present at a concentration sufficient to provide said sustained-release composition with structural stability after being cross-linked, but not at so great a concentration as to render said sustained-release composition (i) incapable of biodegradation or (ii) incapable of permitting the release of said active agent.
A method for the administration of an active agent, wherein said method comprises the administration of a biodegradable sustained-release composition, said sustained-release composition comprising:
- (1) a plasticizing agent, wherein said plasticizing agent is selected from the group consisting of a phthalate ester, a phosphate ester, a glycol derivative, a hydrocarbon, an oil, and a fatty acid;
- (2) said active agent, wherein said active agent is present in an amount sufficient to impart a desired therapeutic, agricultural or catalytic property to said sustained-release composition;
- (3) a cross-linking agent, wherein said cross-linking agent is selected from the group consisting of aldehydes, alcohols, aluminum, chromium, titanium, zirconium, an acyl chloride, bis-diazobenzidine, phenol-2,4-disulfonyl chloride, 1,5-difluoro-2,4-dinitrobenzene, urea, 3,6-bis(mercurimethyl)-dioxane urea, dimethyl adipimidate and N,N'-ethylene-bis-iodacetamide;
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- (4) a biodegradable polymeric matrix comprising a cross-linked, water-insoluble protein, wherein said matrix formed upon the cross-linking of a water-soluble protein, and wherein said cross-linked, water-insoluble protein is present at a concentration sufficient to provide said sustained-release composition with structural stability after being cross-linked, but not at so great a concentration as to render said sustained-release composition (i) incapable of biodegradation or (ii) incapable of permitting the release of said active agent.
Dependencies are inferred from the claim text.