A biodegradable, non-porous medical device and methods for its manufacture and use

Claims

1. A biodegradable non-porous medical device (1) comprising: (a) sheet structural layer (2); and (b) a multilayer water-activated adhesive component (3) comprising fibrinogen (6) proximal to said structural layer (2), carboxymethylcellulose (CMC) (5) and a thrombin layer (4) distal to said structural layer, wherein said multilayer water-activated adhesive component (3) is attached to only one side of said sheet-like structural layer (2), and wherein a linker (7) covalently connects said fibrinogen to said structural layer.

2. A biodegradable non-porous medical product (1) according to claim 1, wherein said sheet structural layer (2) is a flexible plasma-based film or a flexible cryoprecipitate-based film.

3. A biodegradable non-porous medical device (1) according to claim 2, wherein said plasma-based film contains from 0.5 to 10 international units (IU) of thrombin per ml of plasma, has a thickness in the range of 0.005 to 0.1 mm and is characterized by a burst pressure of 50 to 1000 mmHg.

4. A biodegradable non-porous medical device (1) according to claim 2, wherein said cryoprecipitate-based film contains from 0.5 to 10 international units (IU) of thrombin per ml of cryoprecipitate solution, has a thickness in the range of 0.005 to 0.1 mm and is characterized by a burst pressure of 50 to 1000 mmHg.

5. A biodegradable non-porous medical device (1) according to any one of claims 1 to 4, wherein said linker (7) is a non-reactive linker derived from an NHS ester.

6. A biodegradable non-porous medical device (1) according to claim 5, wherein said non-reactive linker derived from an NHS ester is a linker derived from bis-N-succinimidyl diglycolic acid ((DIG(NHS)2).

7. A biodegradable non-porous medical device (1) according to any one of claims 1 to 6, wherein said thrombin layer (4) contains from about 15 to about 30 international units (IU) of thrombin per cm 2 , preferably from about 15 to about 30 international units (IU) of thrombin per cm 2 , or approximately 20 IU of thrombin per cm 2 the specified sheet structural layer (2).

8. A biodegradable non-porous medical product (1) according to any one of paragraphs 1-7, wherein said adhesive component (3) contains: (a) from 5 to 20 mg of fibrinogen (6) per cm 2 of the said sheet structural layer (2), preferably from 8 to 12 mg fibrinogen per cm 2 or 10 mg fibrinogen per cm 2 ; And (b) 5 to 20 mg SMS (5) per cm 2 of the said sheet structural layer (2), preferably from 8 to 12 mg SMS per cm 2 or 10 mg SMS per cm 2 .

9. A biodegradable non-porous medical product (1) according to any one of claims 1-8, wherein said one side of the sheet structural layer (2), to which the adhesive component (3) is bonded, ensures fixation of the product (1) when placed at the site of application, preferably at the site of injury, trauma or surgical intervention.

10. A biodegradable non-porous medical product (1) according to claim 9, in which the opposite side of said sheet structural layer (2) provides said product (1) with the function of an adhesion barrier.

11. A method for producing a biodegradable non-porous medical device (1) according to any of the preceding claims, comprising the steps of: (a) obtaining a sheet structural layer (2); (b) attaching a multilayer water-activated adhesive component (3) to only one side of said sheet structural layer (2), where said attaching comprises (i) covalently attaching fibrinogen (6) to said only one side of said sheet-like structural layer (2) so that a layer of fibrinogen (6) is formed; and (ii) applying thrombin (4) to said fibrinogen layer under anhydrous conditions; and, optionally, (c) drying said biodegradable non-porous medical device (1).

12. A method for producing a biodegradable non-porous medical product (1) according to claim 11, wherein said structural layer (2), which is to be obtained in step (a), is: - a plasma-based film containing from 0.5 to 10 international units (IU) of thrombin per ml of plasma, having a thickness in the range of 0.005 to 0.1 mm and characterized by a burst pressure of from 50 to 1000 mmHg; or - a cryoprecipitate-based film containing from 0.5 to 10 international units (IU) of thrombin per ml of cryoprecipitate solution, having a thickness in the range of 0.005 to 0.1 mm and characterized by a burst pressure of 50 to 1000 mmHg.

13. A method for producing a biodegradable non-porous medical article (1) according to claim 11 or 12, wherein said step (b)(i) comprises covalently coupling said fibrinogen (6) to said one side of said structural layer (2) using a suitable cross-linking agent, preferably the cross-linking agent is a multi-reactive NHS ester, such as an NHS ester containing several reactive groups capable of chemically reacting with amine groups.

14. A method for producing a biodegradable non-porous medical device (1) according to claim 13, wherein said cross-linking agent is bis-N-succinimidyl diglycolic acid (DIG(NHS); CAS-No. 373614-12-1).

15. A method for producing a biodegradable non-porous medical product (1) according to any one of paragraphs 11-14, in which - the specified stage (b)(i) includes: - applying a layer of a multi-reactive crosslinking agent, which is capable of chemically reacting with amine groups, to only one side of said sheet structural layer (2) under anhydrous conditions, preferably by applying glycerol and DIG(NHS)2; and - applying a layer of fibrinogen (6) to said one side of said sheet-like structural layer (2) in the presence of water, preferably by applying an aqueous solution containing carboxymethylcellulose (CMC) (5), fibrinogen (6) and glycerol, wherein the presence of water allows the cross-linking agent to react with the amine groups present on the surface of said one side of the sheet-like structural layer (2) and with the amine groups of said fibrinogen (6), for example, to covalently bind said fibrinogen (6) to said sheet-like structural layer (2); - removal of residual water; and - the specified stage (b)(ii) includes: - application of thrombin (4) in a solution of 0.1 to 2% polyvinylpyrrolidone in dry ethanol to the specified fibrinogen layer (6).