Thermally reversible implant and filler

• US 7,160,931 B2
• Filed: 05/02/2003
• Issued: 01/09/2007
• Est. Priority Date: 03/15/2000
• Status: Expired due to Fees

• Current Assignee: Hai-Hui Lin, John L. Semple, Michael H. May, Yu-Ling Cheng
• Original Assignee: Hai-Hui Lin, John L. Semple, Michael H. May, Yu-Ling Cheng
• Inventors: Cheng, Yu-Ling, Lin, Hai-Hui, May, Michael H., Semple, John L.
• Primary Examiner(s): Yoon; Tae H.
• Application Number:
  US10/428,520
• Publication Number:
  US 20040029994A1
• Time in Patent Office: 1,348 Days
• Field of Search: 523/113, 524/504, 524/505
• US Class Current: 523/113
• CPC Class Codes: A61L 24/06 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043, A61L24/046 take precedence
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: C08F 283/06 on to polyethers, polyoxymethylenes or polyacetals C08F283/004 takes precedence
• CPC Class Codes: C08F 293/00 Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule on to polymers modified by introduction of unsaturated end groups C08F290/02
• CPC Class Codes: C08F 297/00 Macromolecular compounds obtained by successively polymerising different monomer systems using a catalyst of the ionic or coordination type without deactivating the intermediate polymer
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 2666/24 Graft or block copolymers according to groups C08L51/00, C08L53/00 or C08L55/02; Derivatives thereof
• CPC Class Codes: C08L 33/26 Homopolymers or copolymers of acrylamide or methacrylamide
• CPC Class Codes: C08L 51/003 grafted on to macromolecular compounds obtained by reactions only involving unsaturated carbon-to-carbon bonds C08L51/04, C08L51/06 take precedence
• CPC Class Codes: C08L 51/08 grafted on to macromolecular compounds obtained otherwise than by reactions only involving unsaturated carbon-to-carbon bonds
• CPC Class Codes: C08L 53/00 Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 53/005 Modified block copolymers

Abstract

The invention relates to the use of a thermal reversible gel, such as a copolymer composition, as a biological filler or implant. The gel has a semi-solid form at body temperature, but upon cooling to a temperature below a threshold level, the gel is liquefied and can be re-shaped, re-sized, manipulated or removed from the body. The gel may be used as a subcutaneous implant, a biological filler, joint or tissue spacer, for wrinkle filling or other cosmetic implants, as a soft-tissue replacement for reconstructive surgery, or as a barrier within the lumen of a biological structure, such as a blood vessel. The implant may be used to provide reversible birth control by providing, for example, a reversible barrier to the cervix or a reversible blockage of the lumen of the vas deferens.

Claims

1. A method of forming a removable implant in an animal comprising inserting a thermally reversible gel into said animal, said gel having a semi-solid form at body temperature and a liquid form upon cooling to a temperature below a threshold temperature, said threshold temperature being at least 5°

C. below body temperature, wherein said gel comprises a star copolymer and a solvent, the copolymer having the star-shaped structure A(B)n with n>

2, wherein

A is soluble in the solvent, and is selected from the group consisting of polyethylene glycol (PEG), polyvinyl pyrrolidone, polyvinyl alcohol, polyhydroxyethylmethacrylate, and hyaluronic acid; and

B is convertible between soluble and insoluble in the solvent when heated to a temperature between ambient temperature and body temperature, and comprises poly-N-isopropyl acrylamide (PNIPAAm), hydroxypropylmethyl cellulose and other methyl celluloses, poly(ethylene glycol vinyl ether-co-butyl vinyl ether), polymers of N-alkyl acrylamides, poly(amino acid)s, peptide sequences, poly(methacryloyl-L-alanine methyl ester), poly(methacryloyl-L-alanine ethyl ester) or nitrocellulose; and

wherein said gel is reversibly convertible between said semi-solid and said liquid form as a function of temperature.

2. The method of claim 1 wherein the gel is liquefied, and thus re-shapeable, re-sizable, or removable at a temperature below the threshold temperature.

3. The method of claim 1 wherein the implant comprises a gel placed within the lumen of the vas deferens for birth control.

4. The method of claim 1 wherein the implant comprises a cervical seal for birth control.

5. The method of claim 1 wherein the implant comprises a wrinkle filler, a joint spacer, a tissue spacer, a tissue expander, a vessel blocker, a cosmetic enhancer, or a breast implant filler.

6. The method of claim 1, additionally comprising the step of removing the implant by cooling the body in the region of the implant to a temperature below the threshold temperature and extracting the implant.

8. The method of claim 1, wherein A is selected from the group consisting of polyethylene glycol (PEG), polyvinyl pyrrolidone, and polyvinyl alcohol, polyhydroxyethylmethacrylate.

9. The method of claim 1, wherein A is PEG.

10. The method of claim 1, wherein B is PNIPAAm.

11. The method of claim 1, wherein the copolymer is present in the aqueous solution at a level of from 5 to 50% by weight.

12. The method of claim 1, wherein the copolymer is present in the aqueous solution at a level of from 10 to 25% by weight.

13. The method of claim 1, wherein the copolymer is present in the aqueous solution at a level of 20% by weight.

14. The method of claim 12, wherein the copolymer is present in the aqueous solution at a level of from 15 to 25% by weight.

7. A method of forming an in situ implant or an implant in vitro comprising the steps of:

(i) forming a gelable composition comprising a star copolymer and an aqueous solvent, the copolymer having the star-shaped structure A(B)n with n>

2, wherein

A is soluble in the solvent, and is selected from the group consisting of polyethylene glycol (PEG), polyvinyl pyrrolidone, polyvinyl alcohol, polyhydroxyethylmethacrylate, and hyaluronic acid; and

B is convertible from soluble to insoluble when heated to a temperature between ambient temperature and body temperature, and comprises poly-N-isopropyl acrylamide (PNIPAAm), hydroxypropylmethyl cellulose and other methyl celluloses, poly(ethylene glycol vinyl ether-co-butyl vinyl ether), polymers of N-alkyl acrylamides, poly(amino acid)s, peptide sequences, poly(methacryloyl-L-alanine methyl ester), poly(methacryloyl-L-alanine ethyl ester) or nitrocellulose;

the composition being reversibly convertible from liquid to gel when B is insoluble; and

(ii) inserting said composition into a subject to form an in situ implant or heating said composition to at least said gelling temperature to form an in vitro implant.