Biodegradable cross-linkers having a polyacid connected to reactive groups for cross-linking polymer filaments
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12N-011/02
C12N-011/00
A61K-009/14
C07K-017/00
C07K-017/02
출원번호
US-0338404
(1999-06-22)
발명자
/ 주소
Kiser, Patrick F.
Thomas, Allen A.
출원인 / 주소
Access Pharmaceuticals, Inc.
대리인 / 주소
Jackson Walker LLP
인용정보
피인용 횟수 :
37인용 특허 :
101
초록▼
Biodegradable cross-linkers are provided having a polyacid core with at least two acidic groups covalently connected to reactive groups usable to cross-link polymer filaments. Between at least one reactive group and an acidic group of the polyacid is a biodegradable region which preferably consists
Biodegradable cross-linkers are provided having a polyacid core with at least two acidic groups covalently connected to reactive groups usable to cross-link polymer filaments. Between at least one reactive group and an acidic group of the polyacid is a biodegradable region which preferably consists of a hydroxyalkyl acid ester sequence having 1, 2, 3, 4, 5 or 6 hydroxyalkyl acid ester groups. The polyacid may be attached to a water soluble region that is attached to the biodegradable region having attached reactive groups. The hydroxyalkyl acid ester group is preferably a lactate or glycolate. Polyacids include diacids, triacids, tetraacids and pentaacids, and the reactive group may contain a carbon-carbon double bond. A network of cross-linked polymer filaments having adefined biodegradation rate can be formed using the cross-linkers. The network may contain biologically active molecules, and can be in the form of a microparticle or nanoparticle, or hydrogel. The polymer filaments may be preformed polymer filaments of polynucleic acids, polypeptides, proteins or carbohydrates. The cross-linkers may be copolymerized with charged monomers such as acrylic monomers containing charged groups. Applications of the cross-linkers and network include controlled release of drugs and cosmetics, tissue engineering, wound healing, hazardous waste remediation, metal chelation, swellable devices for absorbing liquids and prevention of surgical adhesions.
대표청구항▼
Biodegradable cross-linkers are provided having a polyacid core with at least two acidic groups covalently connected to reactive groups usable to cross-link polymer filaments. Between at least one reactive group and an acidic group of the polyacid is a biodegradable region which preferably consists
Biodegradable cross-linkers are provided having a polyacid core with at least two acidic groups covalently connected to reactive groups usable to cross-link polymer filaments. Between at least one reactive group and an acidic group of the polyacid is a biodegradable region which preferably consists of a hydroxyalkyl acid ester sequence having 1, 2, 3, 4, 5 or 6 hydroxyalkyl acid ester groups. The polyacid may be attached to a water soluble region that is attached to the biodegradable region having attached reactive groups. The hydroxyalkyl acid ester group is preferably a lactate or glycolate. Polyacids include diacids, triacids, tetraacids and pentaacids, and the reactive group may contain a carbon-carbon double bond. A network of cross-linked polymer filaments having adefined biodegradation rate can be formed using the cross-linkers. The network may contain biologically active molecules, and can be in the form of a microparticle or nanoparticle, or hydrogel. The polymer filaments may be preformed polymer filaments of polynucleic acids, polypeptides, proteins or carbohydrates. The cross-linkers may be copolymerized with charged monomers such as acrylic monomers containing charged groups. Applications of the cross-linkers and network include controlled release of drugs and cosmetics, tissue engineering, wound healing, hazardous waste remediation, metal chelation, swellable devices for absorbing liquids and prevention of surgical adhesions. t the cell structure from 10 mV to 100 V. 12. The method according to claim 6, wherein the distance between the two microelectrodes is less than 10 mm. 13. The method according to claim 12, wherein the distance is less than 100 μm. 14. The method according to claim 13, wherein the distance is less than 20 μm. 15. The method according to claim 1, 2, or 3, wherein the diameter of the end is at the at least one microelectrode is less than 1 μm. 16. The method according to claim 1, 2, or 3, wherein the electric field is applied by a rectangular DC voltage pulse. 17. The method according to claim 1 or 2, further comprising contacting the cell with cell-impermeable solutes, wherein the cell-impermeable solutes are transported through pores created in the cell by the electroporation. 18. The method according to claim 3, further comprising contacting the cell structure with cell-impermeable solutes, wherein the cell-impermeable solutes are transported through pores created in the cell structure by the electroporation. 19. The method according to claim 17, wherein the solutes are comprised in an extracellular medium. 20. The method according to claims 18, wherein the solutes before the electroporation are comprised in a medium entrapped in the cell structure. 21. The method according to claim 17, wherein the solutes comprise a pharmaceutically active compound. 22. The method according to claim 18, wherein the solutes comprise a pharmaceutically active compound. 23. The method according to claim 17, wherein the medium comprising the solutes is delivered to the cell by use of a catheter. 24. The method according to claim 1, 2, or 3, wherein at least one microelectrode is a carbon fiber electrode. 25. The method according to claim 1, 2, or 3, wherein at least one microelectrode comprises a hollow electrolyte-filled capillary. 26. The method according to claim 25, wherein a medium comprising cell impermeable solutes is delivered through the hollow electrolyte-filled capillary. 27. The method according to claim 25, wherein the electrolyte comprises a physiological buffer. 28. The method according to claim 17, wherein solutes are delivered to the cell by electrophoresis or electroosmosis. 29. The method according to claim 18, wherein solutes are delivered to the cell structure by electrophoresis or electroosmosis. 30. A method according to claim 25, wherein the hollow electrolyte-filled capillary comprises a fused silica capillary. 31. The method according to claim 30, wherein the fused silica capillary comprises a conductive tip. 32. The method according to claim 25, wherein the capillary comprises a tapered tip. 33. The method according to claim 31, wherein the capillary comprises a tapered tip. 34. The method according to claim 21, wherein the pharmaceutically active compound is a drug. 35. The method according to claim 22, wherein the pharmaceutically active compound is a drug. 36. The method according to claim 21, wherein the pharmaceutically active compound is a nucleic acid. 37. The method according to claim 22, wherein the pharmaceutically active compound is a nucleic acid. 38. The method according to claim 1 or 2, wherein a biological marker or dye is transported into the cell when the cell is permeabilized. 39. The method according to claim 3, wherein a biological marker or dye is transported into the cell structure when the cell structure is permeabilized. 40. The method according to claim 1 or 2, wherein a nanoparticle is transported into the cell when the cell is permeabilized. 41. The method according to claim 3, wherein a nanoparticle is transported into the cell structure when the cell is permeabilized. 42. The method according to claim 8, wherein the organelle is a cell nucleus or mitochondria. 43. The method according to claim 1, 2, or 3, further comprising the step of detecting a cellular response as a result of the electroporation. 44. The method according to claim 43, wherein the cellular response is a change in level
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