Adhesion-preventing composition

Patent metadata

Field	Value
Publication number	US-11464597-B2
Application number	US-201716316097-A
Country	US
Kind code	B2
Filing date	Jul 13, 2017
Priority date	Jul 13, 2016
Publication date	Oct 11, 2022
Grant date	Oct 11, 2022

Abstract

[Problem] An adhesion-preventing material having a high adhesion-preventing effect has been demanded.[Solution] An adhesion-preventing material including a sterilized biocompatible sponge-like laminate, wherein the sponge-like laminate comprises a sponge-like first layer and a sponge-like second layer each of which is at least partially crosslinked with a curing agent and comprises a low-endotoxin alginic acid monovalent metal salt, the alginic acid monovalent metal salt in the first layer has a weight average molecular weight of 10,000 to 2,000,000, the alginic acid monovalent metal salt in the second layer has a weight average molecular weight of 1,000 to 1,000,000, the weight average molecular weights are measured by a GPC-MALS method after a decrosslinking treatment, and the weight average molecular weight of the alginic acid monovalent metal salt in the first layer is higher than that in the second layer.

First claim

The invention claimed is:

1. An adhesion-preventing material comprising a sterilized biocompatible lyophilized sponge-like laminate that includes first and second sponge-like layers containing low-endotoxin monovalent metal salts of alginic acid which are at least partially crosslinked with a curing agent,
wherein a weight average molecular weight of the monovalent metal salt of alginic acid in the first layer is 25,000-500,000,
a weight average molecular weight of the monovalent metal salt of alginic acid in the second layer is 3,000-100,000,
the weight average molecular weights are measured by GPC-MALS method following a decrosslinking treatment, and
the weight average molecular weight of the monovalent metal salt of alginic acid in the first layer is higher than the weight average molecular weight of the monovalent metal salt of alginic acid in the second layer.

2. The adhesion-preventing material according to claim 1 , wherein either one of the first layer and the second layer contains a curing agent.

3. The adhesion-preventing material according to claim 1 , wherein both of the first layer and the second layer contain a curing agent.

4. The adhesion-preventing material according to claim 1 , wherein the total amount of the low-endotoxin monovalent metal salts of alginic acid used in the first layer and the second layer is in a range of 0.1 mg/cm 2 -3 mg/cm 2 .

5. The adhesion-preventing material according to claim 1 , wherein the endotoxin content of the monovalent metal salts of alginic acid in the first layer and the second layer is 500 EU/g or less.

6. The adhesion-preventing material according to claim 1 , wherein the monovalent metal salts of alginic acid in the first layer and the second layer are sodium alginate or potassium alginate.

7. The adhesion-preventing material according to claim 1 , wherein the curing agent in the first layer and the second layer is at least one metal ionic compound selected from the group consisting of CaCl 2 , CaSO 4 , ZnCl 2 , SrCl 2 , FeCl 3 and BaCl 2 .

8. The adhesion-preventing material according to claim 1 , wherein the adhesion-preventing material is mixed or impregnated with a drug.

9. An adhesion-preventing material comprising a biocompatible lyophilized sponge-like laminate which includes a first layer and a second layer each containing a low-endotoxin monovalent metal salt of alginic acid which is at least partially crosslinked with a curing agent, wherein a dissolution rate of the first layer is slower than that of the second layer,
wherein a weight average molecular weight of the monovalent metal salt of alginic acid in the first layer is 25,000-500,000,
a weight average molecular weight of the monovalent metal salt of alginic acid in the second layer is 3,000-100,000,
the weight average molecular weights are measured by GPC-MALS method following a decrosslinking treatment.

10. The adhesion-preventing material according to claim 9 , wherein, in a dissolution test that uses elution of a monovalent metal salt of alginic acid in a phosphate buffer solution at pH 7.5 as an indicator, a ratio of the elution amount of the monovalent metal salt of alginic acid in the first layer is less than 50% after an hour and less than 70% after two hours following the start of the measurement, when taking the elution amount of the monovalent metal salt of alginic acid in the second layer as a base of 100%.

11. The adhesion-preventing material according to claim 9 , wherein, in a dissolution test that uses elution of a monovalent metal salt of alginic acid in a phosphate buffer solution at pH 7.5 as an indicator, the monovalent metal salt of alginic acid in the first layer is eluted for 25±10 wt % within an hour and for 80±10 wt % within 4 hours while the monovalent metal salt of alginic acid in the second layer is eluted for 70±10 wt % within an hour and for 90±10 wt % within 4 hours.

12. The adhesion-preventing material according to claim 1 , wherein the sponge-like laminate is pressed.

13. The adhesion-preventing material according to claim 9 , wherein the adhesion-preventing material is mixed or impregnated with a drug.

14. A biocompatible lyophilized sponge-like laminate obtained by the following steps (1)-(4):
(1) curing a low-endotoxin monovalent metal salt of alginic acid with a weight average molecular weight of 25,000-500,000 with a curing agent;
(2) freezing the cured monovalent metal salt of alginic acid;
(3) curing a low-endotoxin monovalent metal salt of alginic acid with a weight average molecular weight of 3,000-100,000 with a curing agent on the monovalent metal salt of alginic acid obtained in (2) to obtain a laminate; and
(4) lyophilizing the resulting laminate to obtain a sponge-like laminate,
wherein the molecular weights are measured by GPC-MALS method, the sponge-like laminate includes a first sponge-like layer containing the low-endotoxin monovalent metal salt of alginic acid with a weight average molecular weight of 25,000-500,000 and a second sponge-like layer containing the low-endotoxin monovalent metal salt of alginic acid with a weight average molecular weight of 3,000-100,000, and the weight average molecular weight of the monovalent metal salt of alginic acid in the first layer is higher than that in the second layer.

15. The biocompatible sponge-like laminate according to claim 14 , wherein the sponge-like laminate is mixed or impregnated with a drug.

16. A method for preventing an adhesion, comprising a step of applying a sterilized biocompatible lyophilized sponge-like laminate that includes first and second sponge-like layers containing low-endotoxin monovalent metal salts of alginic acid which are at least partially crosslinked with a curing agent, wherein a weight average molecular weight of the monovalent metal salt of alginic acid in the first layer is 25,000-500,000, a weight average molecular weight of the monovalent metal salt of alginic acid in the second layer is 3,000-100,000, the weight average molecular weights are measured by GPC-MALS method following a decrosslinking treatment, and the weight average molecular weight of the monovalent metal salt of alginic acid in the first layer is higher than the weight average molecular weight of the monovalent metal salt of alginic acid in the second layer, to a subject in need of adhesion prevention such that the first layer faces the surface of a wound.

17. A method for producing an adhesion-preventing material comprising a biocompatible lyophilized sponge-like laminate, the method comprising the steps of:
(1) curing a low-endotoxin monovalent metal salt of alginic acid with a weight average molecular weight of 25,000-500,000 with a curing agent;
(2) freezing the cured monovalent metal salt of alginic acid;
(3) curing a low-endotoxin monovalent metal salt of alginic acid with a weight average molecular weight of 3,000-100,000 with a curing agent on the monovalent metal salt of alginic acid obtained in (2) to obtain a laminate; and
(4) lyophilizing the resulting laminate to obtain a sponge-like laminate,
wherein the molecular weights are measured by GPC-MALS method, the sponge-like laminate includes a first sponge-like layer containing the low-endotoxin monovalent metal salt of alginic acid with a weight average molecular weight of 25,000-500,000 and a second sponge-like layer containing the low-endotoxin monovalent metal salt of alginic acid with a weight average molecular weight of 3,000-100,000, and the weight average molecular weight of the monovalent metal salt of alginic acid in the first layer is higher than that in the second layer.

Assignees

• Mochida Pharm Co Ltd
• Univ Tokyo

Inventors

• Ito Taichi
• Ohta Seiichi
• Kokudo Norihiro
• Isaji Mitsuko
• Shimizu Satoshi

Classifications

• A61L31/146 Primary

  Porous materials, e.g. foams or sponges · CPC title

• A61L2420/08

  Coatings comprising two or more layers · CPC title

• A61L31/12

  Composite materials, i.e. containing one material dispersed in a matrix of the same or different material · CPC title

• A61L31/14

  Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} · CPC title

• A61B90/08 Primary

  Accessories or related features not otherwise provided for · CPC title