IPC분류정보
국가/구분 |
United States(US) Patent
등록
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국제특허분류(IPC7판) |
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출원번호 |
US-0403942
(2003-03-28)
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발명자
/ 주소 |
- Martin, David P.
- Skraly, Frank
- Williams, Simon F.
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출원인 / 주소 |
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대리인 / 주소 |
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인용정보 |
피인용 횟수 :
50 인용 특허 :
27 |
초록
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Biocompatible polyhydroxyalkanoate compositions with controlled degradation rates have been developed. In one embodiment, the polyhydroxyalkanoates contain additives to alter the degradation rates. In another embodiment, the polyhydroxyalkanoates are formed of mixtures of monomers or include pendant
Biocompatible polyhydroxyalkanoate compositions with controlled degradation rates have been developed. In one embodiment, the polyhydroxyalkanoates contain additives to alter the degradation rates. In another embodiment, the polyhydroxyalkanoates are formed of mixtures of monomers or include pendant groups or modifications in their backbones to alter their degradation rates. In still another embodiment, the polyhydroxyalkanoates are chemically modified. Methods for manufacturing the devices which increase porosity or exposed surface area can be used to alter degradability. For example, as demonstrated by the examples, porous polyhydroxyalkanoates can be made using methods that creates pores, voids, or interstitial spacing, such as an emulsion or spray drying technique, or which incorporate leachable or lyophilizable particles within the polymer. Examples describe poly(4HB) compositions including foams, coatings, meshes, and microparticles. As demonstrated by the examples, these polyhydroxyalkanoate compositions have extremely favorable mechanical properties, as well as are biocompatible and degrade within desirable time frames under physioogical conditions. These polyhydroxyalkanoate materials provide a wider range of polyhydroxyalkanoate degradation rates than are currently available. Methods for processing these materials, particularly for therapeutic, prophylactic or diagnostic applications, or into devices which can be implanted or injected, are also described.
대표청구항
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1. A method for preparing a biocompatible biodegradable polyhydroxyalkanoate composition that has a controlled degradation rate under physiological conditions, wherein the mass loss, as measured bvxas chromatography, is greater than 5% over a six week period in vivo, or wherein the average molecular
1. A method for preparing a biocompatible biodegradable polyhydroxyalkanoate composition that has a controlled degradation rate under physiological conditions, wherein the mass loss, as measured bvxas chromatography, is greater than 5% over a six week period in vivo, or wherein the average molecular mass loss, as measured by gel permeation chromatography, decreases 20% to 50% over a ten week period in vivo, comprising(a) incorporating monomeric units as chemical linkages into the polymer backbone which alter the chemical stability of the polymer backbone; (b) replacing linkages in said polymer backbone which alter the chemical stability of the polymer backbone; (c) incorporating pendant groups into the polymer which alter the chemical stability of the polymer backbone; (d) incorporating additives which alter the chemical stability of the polymer; or (e) combinations thereof. 2. The method of claim 1 further comprising forming the polyhydroxyalkanoate composition using a method selected from the group consisting of fermentation, enzymatic synthesis, chemical synthesis, melt processing, reactive blending, and recombinant techniques.3. The method of claim 2 wherein the composition is derived by fermentation using a co-feed.4. The method of claim 2 wherein the fermentation process uses transgenic bacteria.5. The method of claim 2 wherein the chemical synthesis is selected from the group consisting of insertion, transesterification and metathesis.6. The method of claim 1 wherein the presence of the additional unit(s) promotes chain scission.7. The method of claim 1 wherein the units contain more than two functional groups.8. The method of claim 1 wherein a heteroatom grouping is incorporated into the polymer backbone chain.9. The method of claim 8 wherein the heteroatom grouping is selected from the group consisting of oxygen, sulfur and nitrogen.10. The method of claim 1 wherein the units are incorporated into the polymer backbone with chemical linkages selected from the group consisting of ester, amide, ether, carbamate, anhydride, and carbonate.11. The method of claim 1 wherein the units are selected from the group consisting of 2-hydroxyacids; 2-hydroxyalkoxyacetic acids; amino acids; amino alcohols; diacids; triols; and tetraols.12. The method of claim 11 wherein the 2-hydroxyacids are 2-hydroxyalkanoic acids.13. The method of claim 12 wherein the 2-hydroxyalkanoic acid is lactic acid.14. The method of claim 12 wherein the 2-hydroxyalkanoic acid is glycolic acid.15. The method of claim 11 wherein the 2-hydroxyacids are 2-hydroxyalkenoic acids.16. The method of claim 11 wherein the 2-hydroxyalkoxyacetic acids are selected from the group consisting of 2-hydroxyethoxy acetic acid and 3-hydroxypropoxy acetic acid.17. The method of claim 1 comprising pendant groups that catalyze the degradation of the polymer backbone.18. The method of claim 17 wherein the pendant groups are selected from acidic and basic groups.19. The method of claim 17 comprising reactant pendant groups that cause polymer chain scission.20. The method of claim 19 wherein the reactant pendant groups are selected from nucleophiles and electrophiles.21. The method of claim 17 wherein the pendant groups are selected from the group consisting of alcohols, acids and amine groups.22. The method of claim 1 wherein the additives promote chain scission.23. The method of claim 22 wherein the additives are selected from the group consisting of acids, bases, electrophiles, nucleophiles, plasticizers, polymers, pore forming agents, and agents designed to reduce the polymer crystallinity.24. The method of claim 23 comprising pore forming agents.25. The method of claim 24 wherein the pore forming agents are lyophilizable particles.26. The method of claim 24 wherein the pore forming agents absorb water.
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