Method for producing a storable molded body made of bacterial cellulose

• US 10,709,820 B2
• Filed: 11/24/2015
• Issued: 07/14/2020
• Est. Priority Date: 11/24/2014
• Status: Active Grant

• Current Assignee: Biotronik AG (Biotronik SE & Company KG)
• Original Assignee: Biotronik AG (Biotronik SE & Company KG)
• Inventors: Ulmer, Jens
• Primary Examiner(s): Ware, Deborah K
• Application Number:
  US15/523,614
• Publication Number:
  US 20170312398A1
• Time in Patent Office: 1,694 Days
• CPC Class Codes: A61B 17/12122 within the heart for closing a cardiac septal defect A61B17/0057
• CPC Class Codes: A61B 2017/00526 Methods of manufacturing
• CPC Class Codes: A61F 2/062 Apparatus for the production of blood vessels made from natural tissue or with layers of living cells prostheses made from natural tissue or living cells A61L27/507
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2/08 Muscles; Tendons; Ligaments sutures A61B17/04
• CPC Class Codes: A61F 2/2409 Support rings therefor, e.g. for connecting valves to tissue annuloplasty rings A61F2/2442
• CPC Class Codes: A61F 2/2412 with soft flexible valve members, e.g. tissue valves shaped like natural valves check valves with flexible valve members in general F16K15/14
• CPC Class Codes: A61F 2/2415 Manufacturing methods
• CPC Class Codes: A61F 2/2418 Scaffolds therefor, e.g. support stents
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2210/0061 swellable
• CPC Class Codes: A61F 2220/0016 with sharp anchoring protrusions, e.g. barbs, pins, spikes
• CPC Class Codes: A61F 2220/0075 sutured, ligatured or stitched, retained or tied with a rope, string, thread, wire or cable
• CPC Class Codes: A61F 2230/0058 X-shaped
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2250/0014 having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
• CPC Class Codes: A61F 2250/0023 differing in porosity
• CPC Class Codes: A61F 2250/0036 differing in thickness
• CPC Class Codes: A61F 2250/0051 differing in tissue ingrowth capacity, e.g. made from both ingrowth-promoting and ingrowth-preventing parts
• CPC Class Codes: A61F 2250/0069 : Sealing means
• CPC Class Codes: A61L 2300/23 : Carbohydrates
• CPC Class Codes: A61L 2300/41 : Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 24/0015 : Medicaments; Biocides
• CPC Class Codes: A61L 24/08 : Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 2400/18 : Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2430/10 : for reconstruction of tendons or ligaments
• CPC Class Codes: A61L 2430/20 : for reconstruction of the heart, e.g. heart valves
• CPC Class Codes: A61L 27/20 : Polysaccharides
• CPC Class Codes: A61L 27/3691 : characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• CPC Class Codes: A61L 27/507 : for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/043 : Polysaccharides
• CPC Class Codes: A61L 29/16 : Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/042 : Polysaccharides
• CPC Class Codes: A61L 31/10 : Macromolecular materials
• CPC Class Codes: A61L 31/146 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61N 1/362 : Heart stimulators heart defibrillators A61N1/39
• CPC Class Codes: A61N 1/3754 : Feedthroughs
• CPC Class Codes: A61N 1/3956 : Implantable devices for applying electric shocks to the heart, e.g. for cardioversion
• CPC Class Codes: B30B 11/005 : Control arrangements
• CPC Class Codes: C12P 19/04 : Polysaccharides, i.e. compounds containing more than five saccharide radicals attached to each other by glycosidic bonds
• CPC Class Codes: D21C 5/00 : Other processes for obtaining cellulose, e.g. cooking cotton linters obtaining fibres for spinning D01C; Processes characterised by the choice of cellulose-containing starting materials

Abstract

A method for producing a storable molded body made of bacterial cellulose and a molded body produced according to the method. A preferred method includes providing a molded body made of bacterial cellulose. Optionally, mechanically pressing the entire molded body or parts of the molded body at temperatures in the range of 10° C. to 100° C. and pressures in the range of 0.01 to 1 MPa for a pressing time of 10-200 min. Treating the molded body with a solution of 20% by weight to 50% by weight of glycerol and 50% by weight to 80% by weight of a C1-C3-alcohol/water mixture. Drying the treated molded body.

Claims

1. A method for producing a storable and swellable molded body made of bacterial cellulose, wherein the method comprises steps of:

providing a molded body of the bacterial cellulose, the bacterial cellulose in the molded body consisting of fibers of bacterial cellulose without foreign polymers;

treating the molded body with a treatment solution comprising

20% by weight to 50% by weight of glycerol and 50% by weight to 80% by weight of a C1-C3-alcohol/water mixture; and

drying the treated molded body.

2. The method according to claim 1, wherein the treatment solution contains a water portion of at most 20% by weight.

3. The method according to claim 1, wherein the molded body is at least a section of an implant shell of an implant.

4. The method according to claim 3, wherein the implant is a cardiac pacemaker or a defibrillator which is stored in the implant shell.

5. The method according to claim 4, wherein the implant shell is a separate pocket for accommodating electrode cables.

6. The method according to claim 1, wherein the molded body is at least a section of a heart valve leaflet of a heart valve prosthesis and/or at least a section of a sealing shell.

7. The method according to claim 6, wherein an outer side of a stent base body of the heart valve prosthesis comprises barbs.

8. The method according to claim 1, wherein the molded body is at least a section of an outer shell and/or inner shell of a stent graft.

9. The method according to claim 8, wherein the inner or outer shell comprises annular sections, which are disposed on the axial ends of the stent graft and exhibit a greater swelling capacity than do sections of the shells located between the two ends.

10. The method according to claim 1, wherein the molded body is a coating of a stent.

11. The method according to claim 1, wherein the molded body is a vascular path, an occluder, or an artificial tendon.

12. The method according to claim 1, further comprising, prior to the step of treating, mechanically pressing the entire molded body or parts of the molded body at temperatures in the range of 10°

C. to 100°

C. and pressures in the range of 0.01 to 1 MPa for a pressing time of 10 -200 min.

13. The method according to claim 1, wherein the bacterial cellulose is bacterial cellulose from Gluconacetobacter xylinus.

14. The method according to claim 1, further comprising producing the molded body of bacterial cellulose, wherein the producing comprises forming layers having different material thicknesses in a culture vessel that comprises a gas-permeable silicone layer having a variable thickness, wherein a culture solution is contacted to the gas-permeable silicon layer.

15. The method according to claim 1, further comprising producing the molded body of bacterial cellulose and cleaning the body of bacterial cellulose, wherein the cleaning comprises killing bacteria with an alkaline surfactant and a base, lysing the bacteria with microwave radiation, neutralizing the molded body, and removing bacterial particles from the molded body.

16. The method according to claim 15, wherein the surfactant concentration is 1 -10% by weight.

17. The method according to claim 15, wherein the base is selected from one or more of the group consisting of sodium hydroxide, potassium hydroxide, alkali and earth alkali carbonates, alkali and earth alkali hydrogencarbonate, ammonia and triethyl amine.

18. The method according to claim 15, wherein the alkaline surfactant is an anionic surfactant.

19. The method according to claim 15, wherein the alkaline surfactant is a nonionic surfactant.

20. The method according to claim 15, wherein the alkaline surfactant is a zwitterionic surfactant.

21. The method according to claim 15, wherein said lysing comprises incubating the body of bacterial cellulose in an enzymatic solution of at least one lytic enzyme at about 37°

C. for at least 15 minutes.

22. A method for producing a storable and swellable molded body made of bacterial cellulose, wherein the method comprises steps of:

providing a molded body of the bacterial cellulose, the bacterial cellulose in the molded body consisting of fibers of bacterial cellulose without foreign polymers;

treating the molded body with a treatment solution comprising

35% by weight to 75% by weight of a C1-C3 alcohol

5% by weight to 25% by weight of water and

20 -50 % by weight of glycerol; and

drying the treated molded body.

23. The method according to claim 22, wherein the C1-C3 alcohol is 2-propanol.

24. A method for producing a storable and swellable molded body made of bacterial cellulose, wherein the method comprises steps of:

providing a molded body made of the bacterial cellulose without foreign polymers;

treating the molded body with a treatment solution comprising

20% by weight to 50% by weight of glycerol and 50% by weight to 80% by weight of a C1-C3-alcohol/water mixture; and

drying the treated molded body, further comprising producing the molded body of bacterial cellulose and cleaning the body of bacterial cellulose, wherein the cleaning comprises;

a) transferring the body of bacterial cellulose into an aqueous solution of 1-10% by weight of at least one surfactant and 0.4 -4% by weight of at least one base,

b) microwave treating the body of bacterial cellulose at a temperature of at least 80°

C., but less than 100°

C., for 30-60 min,

c) washing the body of bacterial cellulose in a solution of aqueous acid in combination with application of microwaves, and rinsing with water.