IPC분류정보
국가/구분 |
United States(US) Patent
등록
|
국제특허분류(IPC7판) |
|
출원번호 |
US-0520414
(2003-07-23)
|
등록번호 |
US-8343472
(2013-01-01)
|
우선권정보 |
AU-2002950340 (2002-07-23) |
국제출원번호 |
PCT/AU03/00935
(2003-07-23)
|
§371/§102 date |
20050106
(20050106)
|
국제공개번호 |
WO2004/009227
(2004-01-29)
|
발명자
/ 주소 |
- Adhikari, Raju
- Gunatillake, Pathiraja A.
|
출원인 / 주소 |
- Polynovo Biomaterials PTY Limited
|
대리인 / 주소 |
Connolly Bove Lodge & Hutz LLP
|
인용정보 |
피인용 횟수 :
0 인용 특허 :
16 |
초록
▼
The present invention relates to biocompatible, biodegradable polyurethane/urea polymeric compositions that are capable of in-vivo curing with low heat generation to form materials suitable for use in scaffolds in tissue engineering applications such as bone and cartilage repair. The polymers are de
The present invention relates to biocompatible, biodegradable polyurethane/urea polymeric compositions that are capable of in-vivo curing with low heat generation to form materials suitable for use in scaffolds in tissue engineering applications such as bone and cartilage repair. The polymers are desirably flowable and injectable and can support living biological components to aid in the healing process. They may be cured ex-vivo for invasive surgical repair methods, or alternatively utilized for relatively non-invasive surgical repair methods such as by arthroscope. The invention also relates to prepolymers useful in the preparation of the polymeric compositions, and to methods of treatment of damaged tissue using the polymers of the invention.
대표청구항
▼
1. A biodegradable, biocompatible polyurethane/urea polymer composition comprising the reaction product of: a) a flowable prepolymer comprising the reaction product of: i) an isocyanate; andii) a low molecular weight multifunctional core molecule having a molecular weight of 400 or less and at least
1. A biodegradable, biocompatible polyurethane/urea polymer composition comprising the reaction product of: a) a flowable prepolymer comprising the reaction product of: i) an isocyanate; andii) a low molecular weight multifunctional core molecule having a molecular weight of 400 or less and at least two functional groups that react with said isocyanate thereby forming urethane or urea groups; andb) a soft segment-forming functional oligomer chosen from: i) linear oligomers;ii) star oligomers;iii) dendrimeric oligomers; andiv) hyperbranched oligomers;wherein the functional oligomer has degradable arms and is selected from the group consisting of lactides, glycolides, lactide/glycolides, caprolactones, propylene fumarates, glycolic acid, dioxanones, anhydrides, polyorthoesters and phosphorylacholines;and wherein the flowable prepolymer is curable with the functional oligomer at 30° C. 2. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, wherein said soft segment forming functional oligomer is zwitterionic. 3. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, comprising the reaction product of water, polycaprolactone triol and a prepolymer wherein said prepolymer comprises the reaction product of pentaerythritol and methyl 2,6-diisocyanato hexanoate. 4. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, comprising the reaction product of water, polycaprolactone triol and prepolymer comprising the reaction product of glucose and methyl 2,6-diisocyanato hexanoate. 5. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, comprising the reaction product of water and polycaprolactone triol and a prepolymer comprising the reaction product of glucose and ethyl 2,6-diisocyanato hexanoate. 6. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, comprising the reaction product of polycaprolactone triol and dihydroxypolycaprolactone phosphoryl choline and a prepolymer comprising the reaction product of pentaerythritol and methyl 2,6-diisocyanato hexanoate. 7. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, comprising the reaction product of polycaprolactone triol and a 1,2-dihydroxy-N,N-dimethylaminopropane sulfonate zwitterion and a prepolymer comprising the reaction product of glucose and methyl 2,6-diisocyanato hexanoate. 8. A biodegradable, biocompatible polymeric scaffold comprising a cured biocompatible, biodegradable polyurethane/urea composition as claimed in claim 3. 9. A biodegradable, biocompatible polymeric scaffold as claimed in claim 8 having a compressive strength in the range of 0.05-80 MPa. 10. A biodegradable, biocompatible polymeric scaffold as claimed in claim 8, having pores in a size range of 150-300 micron. 11. A biodegradable, biocompatible polymeric scaffold as claimed in claim 8, further comprising biological components selected from the group consisting of cells, growth factors, components for supporting cell growth, calcium phosphate, hydroxyapatite, adhesives, fibrin, collagen, transglutaminase systems, surfactants, siloxane surfactants, porogens, silica particles, powdered silica, sugars, sodium chloride, polymeric hollow fibers, and gelatin beads. 12. A process for the preparation of a biocompatible, biodegradable polyurethane/urea composition as claimed in claim 1, comprising reacting an isocyanate with a multifunctional core molecule having a molecular weight less than 400 that reacts with said isocyanate to form urethane or urea groups under suitable conditions to form a prepolymer composition with a flowable viscosity; andreacting said prepolymer with a star soft segment forming functional oligomer with degradable arms and optionally, appropriate amounts of water and catalyst under conditions such that the reaction temperature does not exceed 90° C. 13. A process as claimed in claimed in claim 12 wherein the functional oligomer is soluble in said prepolymer. 14. A method of treatment of damaged bone or cartilage in a patient requiring such treatment, the method comprising administering to said patient a biocompatible, biodegradable polyurethane/urea composition as claimed in claim 1, said administration occurring by the implant of a scaffold formed ex-vivo from a cured form of said polyurethane/urea composition, or by the injection of said polymer in an uncured form for in-vivo curing and scaffold formation. 15. A process of repairing bone or cartilage comprising integrating the scaffold of claim 14 with said bone or cartilage. 16. The process for the preparation of a biocompatible, biodegradable polyurethane/urea composition as claimed in claim 12, wherein the reaction temperature does not exceed 60° C. 17. The process for the preparation of a biocompatible, biodegradable polyurethane/urea composition as claimed in claim 16, wherein the reaction temperature does not exceed 40° C. 18. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, wherein the isocyanate used in formation of said prepolymer is 1,6-hexanediisocyanate. 19. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, wherein the isocyanate used in formation of said prepolymer is isophorone diisocyanate. 20. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, wherein the prepolymer composition is the reaction product of pentaerythritol and ethyl-2,6-diisocyanate hexanoate. 21. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, wherein the prepolymer composition is the reaction product of trimethylol propane and ethyl-2,6-diisocyanate hexanoate. 22. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, wherein the soft segment-forming functional oligomer is polycaprolactone triol. 23. A biodegradable, biocompatible polyurethane/urea polymer composition as claimed in claim 1, wherein the soft segment-forming functional oligomer is formed from pentaerythritol an lactic acid or pentaerythritol and glycolic acid. 24. A biodegradable, biocompatible polymeric scaffold as claimed in claim 8, further comprising progenitor cells. 25. The process for the preparation of a biocompatible, biodegradable polyurethane/urea composition as claimed in claim 12, wherein the multifunctional core molecule has at least three functional groups.
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