MEDICAL HYDROGEL COMPOSITION, AND MEDICAL HYDROGEL, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF

• US 20190142994A1
• Filed: 04/28/2017
• Published: 05/16/2019
• Est. Priority Date: 04/29/2016
• Status: Active Grant

• Current Assignee: Medprin Regenerative Medical Technologies Co., Ltd.
• Original Assignee: Medprin Regenerative Medical Technologies Co., Ltd.
• Inventors: Lin, Limin, Yang, Yaya, Ma, Cheng, Deng, Kunxue, Yuan, Yuyu
• Granted Patent: US 11,065,360 B2
• Time in Patent Office: Days
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: C08L 77/04 Polyamides derived from alpha-amino carboxylic acids C08L77/10 takes precedence
• CPC Class Codes: C08L 79/02 Polyamines

Abstract

A medical hydrogel composition, a medical hydrogel, a preparation method therefore and an application thereof, and a medical hydrogel kit. The medical hydrogel composition comprises a first component and a second component; the first component comprises polylysine and polyethylene imine; the second component comprises one or more of 4-arm-polyethylene glycol-succinimidyl glutarate, 4-arm-polyethylene glycol-succinimidyl succinate, and 4-arm-polyethylene glycol-succinimidyl carbonate; the degree of polymerization of the polylysine is 20 or more. The medical hydrogel is formed by reacting the first component with the second component of the medical hydrogel composition. The medical hydrogel kit comprises the medical hydrogel composition and a buffer solution used for dissolving the components of the medical hydrogel composition. The medical hydrogel has a degree of swelling of −10%-50%, and can be applied in narrow parts where cranial, spinal, and peripheral nerves are densely distributed.

Claims

1. A medical hydrogel composition, wherein the medical hydrogel composition comprises a first component and a second component, the first component comprises polylysine and polyethylene imine, the second component comprises one or more of 4-arm-polyethylene glycol-succinimidyl glutarate, 4-arm-polyethylene glycol-succinimidyl succinate, and 4-arm-polyethylene glycol-succinimidyl carbonate, and wherein the polylysine has a degree of polymerization of 20 or more, preferably 25 to 35.

2. The medical hydrogel composition according to claim 1, wherein in the first component, a mass ratio of the polylysine to the polyethylene imine is 0.1 to 10.

3. The medical hydrogel composition according to claim 1, wherein the polylysine is ε

-polylysine and/or poly-L-lysine.

4. The medical hydrogel composition according to claim 3, wherein the weight average molecular weight of the ε

-polylysine is 3000 to 5000 Da.

5. The medical hydrogel composition according to claim 3, wherein the weight average molecular weight of the poly-L-lysine is 7500 to 300000 Da, preferably 100000 to 200000 Da.

6. The medical hydrogel composition according to claim 1, wherein the number average molecular weight of the polyethylene imine is 1000 to 3500 Da, preferably 1500 to 2000 Da.

7. The medical hydrogel composition according to claim 1, wherein the weight average molecular weights of the 4-arm-polyethylene glycol-succinimidyl glutarate, the 4-arm-polyethylene glycol-succinimidyl succinate, and the 4-arm-polyethylene glycol-succinimidyl carbonate are all 2000 to 40000 Da, preferably 10000 to 20000 Da.

8. The medical hydrogel composition according to claim 1, wherein the medical hydrogel composition is loaded with a drug or an active factor, preferably, the first component and/or the second component contains the drug or the active factor.

9. A medical hydrogel, which is formed by reacting the first component and the second component of the medical hydrogel composition of claim 1;

preferably, the medical hydrogel is formed by reacting the first component and the second component in a buffer solution.

10. The medical hydrogel according to claim 9, wherein the medical hydrogel is formed by dissolving the first component in a first buffer solution, dissolving the second component in a second buffer solution, and then mixing and reacting the two obtained mixtures.

11. The medical hydrogel according to claim 9, wherein the medical hydrogel has a degree of swelling of −

10% to 50%, preferably 5% to 47%.

12. The medical hydrogel according to claim 9, wherein after the medical hydrogel is soaked in water, the pH value of a soaking solution is 7 to 9.5, preferably 7 to 8.

13. The medical hydrogel according to claim 9, wherein the pH value of the first buffer solution is 7.0 to 7.4 or 9.1 to 10.0, preferably 7.0 to 7.4, and the pH value of the second buffer solution is 5.0 to 6.0 or 7.0 to 7.4, preferably 7.0 to 7.4.

14. A preparation method of the medical hydrogel according to claim 9, wherein the preparation method comprises the following steps:

dissolving a first component in a first buffer solution to obtain a first mixed solution;

dissolving a second component in a second buffer solution to obtain a second mixed solution; and

mixing the first mixed solution and the second mixed solution to obtain the medical hydrogel.

15. The preparation method of the medical hydrogel according to claim 14, wherein in the first mixed solution, the concentration of the polylysine is 1 to 50 mg/mL, and the concentration of the polyethylene imine is 1 to 50 mg/mL;

in the second mixed solution, the concentration of the 4-arm-polyethylene glycol-succinimidyl glutarate, the 4-arm-polyethylene glycol-succinimidyl succinate, the 4-arm-polyethylene glycol-succinimidyl carbonate, or a mixture thereof is 100 to 200 mg/mL; and

the first mixed solution and the second mixed solution are mixed in an equal volume to obtain the medical hydrogel.

16. The preparation method of the medical hydrogel according to claim 14, wherein the second mixed solution further comprises a developer, preferably, the developer comprises one or more of FD&

C Blue #1, FD&

C Blue #2, and methylene blue.

17. A medical hydrogel kit, wherein the medical hydrogel kit comprises the medical hydrogel composition of claim 1 and a buffer solution for dissolving each component of the medical hydrogel composition.

18. The medical hydrogel kit according to claim 17, wherein the first component and the second component of the medical hydrogel composition are stored separately, preferably, the polylysine and the polyethylene imine in the first component of the medical hydrogel composition are stored separately.

19. Use of the medical hydrogel according to claim 9 in hemostatic adjuvants, products for pulmonary air leak prevention or cerebrospinal fluid leak prevention, and anti-adhesion products.