Compositions and methods for spinal disc repair and other surgical and non-surgical indications

Patent metadata

Field	Value
Publication number	US-10279079-B2
Application number	US-201214129988-A
Country	US
Kind code	B2
Filing date	Jul 5, 2012
Priority date	Jul 5, 2011
Publication date	May 7, 2019
Grant date	May 7, 2019

Abstract

The present invention features, inter alia, biocompatible compositions that include a poloxamer and one or more additives such as hyaluronic acid, gelatin, fibronectin, or a peptide fragment of fibronectin. The compositions are useful in tissue repair or remodeling, including repair of an injured spinal disc, in drug delivery, in cell culture, and in inhibiting the formation of adhesions.

First claim

What is claimed is:

1. A biocompatible composition comprising 0.002-0.045% (w/v) of hyaluronic acid (HA), gelatin, and 18.182-39.604% (w/v) of a poloxamer, wherein the poloxamer has a hydrophobe base of polyoxy-propylene represented by (C 3 H 6 O) and a formula:
HO(C 2 H 4 O) b (C 3 H 6 O) a (C 2 H 4 O) b H  (II)

wherein a is an integer such that the hydrophobe base has a molecular weight of at least 2,250 and b is an integer from about 8 to 180 or more, wherein, when the hydrophobe has a molecular weight of 2,250 daltons, the gelatin contains at least 40% by weight of the block polymer and b is at least 26, and wherein, when the hydrophobe has a molecular weight of 4,000 daltons, the gelatin contains at least 20% by weight of the block polymer and b is at least 136.

2. The biocompatible composition of claim 1 , wherein the composition is a liquid at 4° C. and a gel at 37° C.

3. The biocompatible composition of claim 1 , wherein the polyoxy-propylene has a molar mass of about 1,000 to about 3,500 g/mol.

4. The biocompatible composition of claim 1 , wherein the poloxamer contains about 30%-90% polyoxyethylene.

5. The biocompatible composition of claim 1 , wherein the composition comprises hyaluronic acid and gelatin mixed in a ratio of about 1:1 (HA:gelatin, v:v).

6. The biocompatible composition of claim 5 , wherein the composition comprises 0.002-0.045% (w/v) of the mixture of hyaluronic acid and gelatin and 27.273-29.703% (w/v) of the poloxamer.

7. The biocompatible composition of claim 1 , wherein the composition is free from chemical cross-linking agents or wherein the poloxamer, hyaluronic acid (HA), and gelatin are not chemically cross-linked.

8. The biocompatible composition of claim 1 , further comprising a detectable label.

9. The biocompatible composition of claim 1 , further comprising a therapeutic agent.

10. The biocompatible composition of claim 9 , wherein the therapeutic agent is an organic compound, nucleic acid, polypeptide, or biological cell.

11. A kit comprising the biocompatible composition of claim 1 and instructions for use.

12. A method of repairing a spinal disc, the method comprising:
(a) identifying a patient in need of treatment; and
(b) applying the biocompatible composition of claim 1 to the area of a damaged spinal disc.

13. A method of inhibiting the formation of adhesions in a patient following a surgical procedure, the method comprising:
(a) identifying a patient in need of treatment; and
(b) applying the biocompatible composition of claim 1 to an area where surgical adhesions are likely to form following a surgical procedure.

14. A biocompatible composition comprising 0.002-0.045% (w/v) of hyaluronic acid (HA), gelatin, or a mixture thereof and 18.182-39.604% (w/v) of a poloxamer, wherein the poloxamer comprises a hydrophobe of polyoxy-propylene represented by (C 3 H 6 O) and a hydrophile of polyoxyethylene represented by (C 2 H 4 O), and wherein the poloxamer has the following formula:

wherein a and b are integers representing the weight percent of the hydrophile (wpH-phile) and the molecular weight of the hydrophobe (mwH-phobe), respectively, wherein, when the a and b integers are plotted on a graph having an abscissa for the wpH-phile extending from 0 to 90 and an ordinate for the mwH-phobe extending from 501-8000, fall within four areas of the graph, a first area having values for a of between 10 and 90 wpH-phile and values for b of between 5501 and 8000 mwH-phobe, a second area having values for a of between 80 and 90 wpH-phile and values for b of between 2501 and 5501 mwH-phobe, a third area bounded on three sides by values for a of from 10 to 40 wpH-phile, values for b of from 2501 to 5501 mwH-phobe, and a first line connecting the a, b coordinates of 10 wpH-phile, 5501 mwH-phobe and 40 wpH-phile, 2501 mwH-phobe, and a fourth area bounded on three sides by values for a from 40 to 80 wpH-phile, values for b from 2001 to 2501 mwH-phobe, and a second line connecting the a, b coordinates of 40 wpH-phile, 2501 mwH-phobe and 80 wpH-phile, 2001 mwH-phobe, and
wherein the polymers have (1) a hydrophobe molecular weight of from about 2,000 to about 8,000 daltons, (2) a hydrophile content of from 10% to 90% by weight of the biocompatible composition, and (3) a total molecular weight of from about 4,000 to 100,000 daltons.

15. The biocompatible composition of claim 14 , wherein the composition is a liquid at 4° C. and a gel at 37° C.

16. The biocompatible composition of claim 14 , wherein the poloxamer comprises polyoxy-propylene having a molar mass of about 1,000 to about 3,500 g/mol.

17. The biocompatible composition of claim 14 , wherein the poloxamer contains about 30%-90% polyoxyethylene.

18. The biocompatible composition of claim 14 , wherein the composition comprises hyaluronic acid and gelatin mixed in a ratio of about 1:1 (HA:gelatin, v:v).

19. The biocompatible composition of claim 18 , wherein the composition comprises 0.002-0.045% (w/v) of the mixture of hyaluronic acid and gelatin and 27.273-29.703% (w/v) of the poloxamer.

Assignees

• Davis Raphael
• Bhatnagar Divya
• Rafailovich Miriam
• Univ New York State Res Found

Inventors

• Davis Raphael
• Bhatnagar Divya
• Rafailovich Miriam

Classifications

• A61L27/52

  Hydrogels or hydrocolloids · CPC title

• A61L27/48 Primary

  with macromolecular fillers · CPC title

• A61L2400/06

  Flowable or injectable implant compositions · CPC title

• A61L27/18 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title

• A61L27/26

  Mixtures of macromolecular compounds · CPC title