CA2353642A1 - Biocompatible crosslinked polymers - Google Patents
Biocompatible crosslinked polymers Download PDFInfo
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- CA2353642A1 CA2353642A1 CA002353642A CA2353642A CA2353642A1 CA 2353642 A1 CA2353642 A1 CA 2353642A1 CA 002353642 A CA002353642 A CA 002353642A CA 2353642 A CA2353642 A CA 2353642A CA 2353642 A1 CA2353642 A1 CA 2353642A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/145—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/91—Polymers modified by chemical after-treatment
- C08G63/912—Polymers modified by chemical after-treatment derived from hydroxycarboxylic acids
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
- C08G63/08—Lactones or lactides
Abstract
Biocompatible crosslinked polymers, and methods for their preparation and us e, are disclosed in which the biocompatible crosslinked polymers are formed fro m water soluble precursors having electrophilic and nucleophilic groups capabl e of reacting and crosslinking in situ. Methods for making the resulting biocompatible crosslinked polymers biodegradable or not are provided, as are methods for controlling the rate of degradation. The crosslinking reactions may be carried out in situ on organs or tissues or outside the body. Applications for such biocompatible crosslinked polymers and their precursor s include controlled delivery of drugs, prevention of post-operative adhesions , coating of medical devices such as vascular grafts, wound dressings and surgical sealants.
Claims (33)
1. A method for preparing a biocompatible crosslinked polymer, comprising:
providing a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
dissolving the biocompatible small molecule crosslinker in a first solvent to form a crosslinker solution;
providing a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic;
dissolving the biocompatible functional polymer in a second solvent to form a functional polymer solution; and combining the crosslinker and functional polymer solutions to react the crosslinker functional groups with the functional polymer functional groups.
providing a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
dissolving the biocompatible small molecule crosslinker in a first solvent to form a crosslinker solution;
providing a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic;
dissolving the biocompatible functional polymer in a second solvent to form a functional polymer solution; and combining the crosslinker and functional polymer solutions to react the crosslinker functional groups with the functional polymer functional groups.
2. The method of claim 1, wherein combining the crosslinker and functional polymer solutions further comprises combining the crosslinker and functional polymer solutions in an animal or human body.
3. The method of claim 1, wherein providing a biocompatible small molecule crosslinker further comprises providing a biocompatible small molecule crosslinker having a solubility of at least 1 g/100 ml in an aqueous solution.
4. The method of claim 1, wherein providing a biocompatible small molecule crosslinker further comprises providing a biocompatible small molecule crosslinker having crosslinker functional groups that are electrophilic.
5. The method of claim 4, wherein providing a biocompatible small molecule crosslinker having crosslinker functional groups that are electrophilic further comprises providing a biocompatible small molecule crosslinker wherein the electrophilic crosslinker functional groups are N-hydroxysuccinimide groups.
6. The method of claim 5, wherein providing a biocompatible functional polymer further comprises providing a biocompatible functional polymer wherein the functional polymer functional groups are amines.
7. The method of claim 1, wherein providing a biocompatible small molecule crosslinker further comprises providing a biocompatible small molecule crosslinker having crosslinker functional groups that are nucleophilic.
8. The method of claim 7, wherein providing a biocompatible small molecule crosslinker having crosslinker functional groups that are nucleophilic further comprises providing a biocompatible small molecule crosslinker wherein the crosslinker functional groups are amines.
9. The method of claim 8, wherein providing a biocompatible functional polymer further comprises providing a biocompatible functional polymer wherein the functional polymer functional groups are N-hydroxysuccinimide groups.
10. The method of claim 1, wherein providing a biocompatible small molecule crosslinker further comprises providing a biocompatible small molecule crosslinker having a biodegradable link.
11. The method of claim 1, wherein providing a biocompatible functional polymer further comprises providing a biocompatible functional polymer having a biodegradable link.
12. The method of claim 1, wherein combining the crosslinker and functional polymer solutions further comprises reacting the crosslinker functional groups and the functional polymer functional groups to produce a biodegradable link.
13. The method of claim 1, further comprising:
providing a visualization agent; and dissolving the visualization agent in the first solvent.
providing a visualization agent; and dissolving the visualization agent in the first solvent.
14. The method of claim 1, further comprising:
providing a visualization agent; and dissolving the visualization agent in the second solvent.
providing a visualization agent; and dissolving the visualization agent in the second solvent.
15. A biocompatible small molecule crosslinker having n functional groups, wherein n is two or more.
16. The biocompatible small molecule crosslinker of claim 15, wherein the biocompatible small molecule crosslinker has a solubility of at least 1 g/100 ml in an aqueous solution.
17. The biocompatible small molecule crosslinker of claim 15, wherein the functional groups are nucleophilic.
18, The biocompatible small molecule crosslinker of claim 17, wherein the functional groups are amines.
19. The biocompatible small molecule crosslinker of claim 15, wherein the biocompatible small molecule crosslinker further comprises a biodegradable link.
20. A biocompatible crosslinked polymer, comprising:
at least one biocompatible small molecule crosslinker regions;
at least one biocompatible functional polymer regions, wherein the biocompatible crosslinked polymer comprises at least three links between the crosslinker regions and the functional polymer regions, and the links are a reaction product of electrophilic functional groups with nucleophilic functional groups.
at least one biocompatible small molecule crosslinker regions;
at least one biocompatible functional polymer regions, wherein the biocompatible crosslinked polymer comprises at least three links between the crosslinker regions and the functional polymer regions, and the links are a reaction product of electrophilic functional groups with nucleophilic functional groups.
21. The biocompatible crosslinked polymer of claim 20, wherein the biocompatible small molecule crosslinker regions each have a solubility of at least 1 g/100 ml in an aqueous solution.
22. The biocompatible crosslinked polymer of claim 20, wherein the biocompatible crosslinked polymer further comprises at least one biodegradable link.
23. The biocompatible crosslinked polymer of claim 20, wherein at least one of the links between the crosslinker and functional polymer regions is biodegradable.
24. A method for preventing surgical adhesions, the method comprising:
providing, at a surgical site, a first solution comprising a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
providing, at the surgical site, a second solution comprising a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic; and combining the first and second solutions to react the crosslinker functional groups with the functional polymer functional groups and produce a biocompatible crosslinked polymer at the surgical site.
providing, at a surgical site, a first solution comprising a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
providing, at the surgical site, a second solution comprising a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic; and combining the first and second solutions to react the crosslinker functional groups with the functional polymer functional groups and produce a biocompatible crosslinked polymer at the surgical site.
25. The method of claim 24, wherein providing a first solution further comprises providing a first solution comprising a biocompatible small molecule crosslinker having a solubility of at least 1 g/100 ml in an aqueous solution.
26. A method for drug delivery comprising:
providing a first solution comprising a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
providing a second solution comprising a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic;
providing a drug;
combining the first and second solutions and the drug to react the crosslinker functional groups with the functional polymer functional groups and produce a biocompatible crosslinked polymer entrapping the drug;
and injecting or implanting the biocompatible crosslinked polymer in an animal or human body.
providing a first solution comprising a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
providing a second solution comprising a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic;
providing a drug;
combining the first and second solutions and the drug to react the crosslinker functional groups with the functional polymer functional groups and produce a biocompatible crosslinked polymer entrapping the drug;
and injecting or implanting the biocompatible crosslinked polymer in an animal or human body.
27. The method of claim 26, wherein providing a first solution further comprises providing a first solution comprising a biocompatible small molecule crosslinker having a solubility of at least 1 g/100 ml in an aqueous solution.
28. A method for drug delivery comprising:
providing, in an animal or human body, a first solution comprising a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
providing, in the body, a second solution comprising a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic;
providing, in the body, a drug; and combining, in the body, the first and second solutions and the drug to react the crosslinker functional groups with the functional polymer functional groups and form a biocompatible crosslinked polymer entrapping the drug.
providing, in an animal or human body, a first solution comprising a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
providing, in the body, a second solution comprising a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic;
providing, in the body, a drug; and combining, in the body, the first and second solutions and the drug to react the crosslinker functional groups with the functional polymer functional groups and form a biocompatible crosslinked polymer entrapping the drug.
29. The method of claim 28, wherein providing a first solution further comprises providing a first solution comprising a biocompatible small molecule crosslinker having a solubility of at least 1 g/100 ml in an aqueous solution.
30. A method for completely or partially blocking, augmenting, sealing or filling a natural or surgically-created void, lumen or space in an animal or human body, the method comprising:
providing a first solution comprising a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
providing a second solution comprising a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic;
combining the first and second solutions solutions to react the crosslinker functional groups with the functional polymer functional groups and produce a biocompatible crosslinked polymer; and injecting or implanting the biocompatible crosslinked polymer in the void, lumen or space.
providing a first solution comprising a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
providing a second solution comprising a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic;
combining the first and second solutions solutions to react the crosslinker functional groups with the functional polymer functional groups and produce a biocompatible crosslinked polymer; and injecting or implanting the biocompatible crosslinked polymer in the void, lumen or space.
31. The method of claim 30, wherein providing a first solution further comprises providing a first solution comprising a biocompatible small molecule crosslinker having a solubility of at least 1 g/100 ml in an aqueous solution.
32. A method for completely or partially blocking, augmenting, sealing or filling a natural or surgically-created void, lumen or space in an animal or human body. the method comprising:
providing, in the void, lumen or space, a first solution comprising a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
providing, in the void, lumen or space, a second solution comprising a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic; and combining the first and second solutions to react the crosslinker functional groups with the functional polymer functional groups and produce a biocompatible crosslinked polymer in the void, lumen or space.
providing, in the void, lumen or space, a first solution comprising a biocompatible small molecule crosslinker having n crosslinker functional groups, wherein n is two or more, and wherein the crosslinker functional groups are either electrophilic or nucleophilic;
providing, in the void, lumen or space, a second solution comprising a biocompatible functional polymer having m functional polymer functional groups, wherein m is two or more and the sum of n and m is five or more, and wherein the functional polymer functional groups are nucleophilic if the crosslinker functional groups are electrophilic, and the functional polymer functional groups are electrophilic if the crosslinker functional groups are nucleophilic; and combining the first and second solutions to react the crosslinker functional groups with the functional polymer functional groups and produce a biocompatible crosslinked polymer in the void, lumen or space.
33. The method of claim 32, wherein providing a first solution further comprises providing a first solution comprising a biocompatible small molecule crosslinker having a solubility of at least 1 g/100 ml in an aqueous solution.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US11084998P | 1998-12-04 | 1998-12-04 | |
US60/110,849 | 1998-12-04 | ||
PCT/US1999/028718 WO2000033764A1 (en) | 1998-12-04 | 1999-12-03 | Biocompatible crosslinked polymers |
Publications (2)
Publication Number | Publication Date |
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CA2353642A1 true CA2353642A1 (en) | 2000-06-15 |
CA2353642C CA2353642C (en) | 2009-11-10 |
Family
ID=22335273
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CA002353642A Expired - Lifetime CA2353642C (en) | 1998-12-04 | 1999-12-03 | Biocompatible crosslinked polymers |
Country Status (6)
Country | Link |
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US (4) | US6566406B1 (en) |
EP (1) | EP1137373A4 (en) |
JP (2) | JP2002531217A (en) |
AU (1) | AU2707500A (en) |
CA (1) | CA2353642C (en) |
WO (1) | WO2000033764A1 (en) |
Families Citing this family (361)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4193917B2 (en) | 1995-12-18 | 2008-12-10 | アンジオデバイス インターナショナル ゲーエムベーハー | Crosslinked polymer composition and method of use thereof |
US6696499B1 (en) * | 1996-07-11 | 2004-02-24 | Life Medical Sciences, Inc. | Methods and compositions for reducing or eliminating post-surgical adhesion formation |
US20090324721A1 (en) * | 1996-09-23 | 2009-12-31 | Jack Kennedy | Hydrogels Suitable For Use In Polyp Removal |
US8003705B2 (en) * | 1996-09-23 | 2011-08-23 | Incept Llc | Biocompatible hydrogels made with small molecule precursors |
US7009034B2 (en) | 1996-09-23 | 2006-03-07 | Incept, Llc | Biocompatible crosslinked polymers |
US6371975B2 (en) | 1998-11-06 | 2002-04-16 | Neomend, Inc. | Compositions, systems, and methods for creating in situ, chemically cross-linked, mechanical barriers |
US20030191496A1 (en) | 1997-03-12 | 2003-10-09 | Neomend, Inc. | Vascular sealing device with microwave antenna |
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-
1999
- 1999-12-03 WO PCT/US1999/028718 patent/WO2000033764A1/en active Application Filing
- 1999-12-03 US US09/454,900 patent/US6566406B1/en not_active Expired - Lifetime
- 1999-12-03 EP EP99968867A patent/EP1137373A4/en not_active Withdrawn
- 1999-12-03 CA CA002353642A patent/CA2353642C/en not_active Expired - Lifetime
- 1999-12-03 JP JP2000586259A patent/JP2002531217A/en active Pending
- 1999-12-03 AU AU27075/00A patent/AU2707500A/en not_active Abandoned
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2003
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- 2003-02-25 US US10/373,939 patent/US20030162841A1/en not_active Abandoned
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2007
- 2007-03-15 JP JP2007066149A patent/JP2007217699A/en active Pending
- 2007-11-16 US US11/985,588 patent/US8535705B2/en active Active
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JP2007217699A (en) | 2007-08-30 |
US20080095736A1 (en) | 2008-04-24 |
US20030162841A1 (en) | 2003-08-28 |
US8535705B2 (en) | 2013-09-17 |
CA2353642C (en) | 2009-11-10 |
US6566406B1 (en) | 2003-05-20 |
EP1137373A4 (en) | 2004-05-19 |
JP2002531217A (en) | 2002-09-24 |
WO2000033764A1 (en) | 2000-06-15 |
EP1137373A1 (en) | 2001-10-04 |
US20040023842A1 (en) | 2004-02-05 |
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