Modified starch material of biocompatible hemostasis

• US 20090062233A1
• Filed: 08/08/2008
• Published: 03/05/2009
• Est. Priority Date: 08/09/2007
• Status: Abandoned Application

• Current Assignee: Xin Ji
• Original Assignee: Xin Ji
• Inventors: Xing, Cheng, Chen, Jianping, Shi, Xueshen, Ji, Xin
• Application Number:
  US12/228,029
• Publication Number:
  US 20090062233A1
• Time in Patent Office: Days
• US Class Current: 514/60
• CPC Class Codes: A61K 31/718 Starch or degraded starch, e.g. amylose, amylopectin
• CPC Class Codes: A61K 31/738 Cross-linked polysaccharides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/0036 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 24/0073 with a macromolecular matrix
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 24/104 Gelatin
• CPC Class Codes: A61L 2400/04 Materials for stopping bleeding
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 26/0023 Polysaccharides
• CPC Class Codes: A61L 26/0085 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/045 Gelatin
• CPC Class Codes: A61L 31/125 having a macromolecular matrix
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: C08B 30/00 : Preparation of starch, degraded or non-chemically modified starch, amylose, or amylopectin
• CPC Class Codes: C08B 30/20 : Amylose or amylopectin chemical derivatives thereof C08B33/00, C08B35/00
• CPC Class Codes: C08B 31/00 : Preparation of derivatives of starch derivatives of amylose C08B33/00; derivatives of amylopectin C08B35/00
• CPC Class Codes: C08B 31/003 : Crosslinking of starch
• CPC Class Codes: C08B 31/02 : Esters
• CPC Class Codes: C08B 31/04 : of organic acids , e.g. alkenyl-succinated starch
• CPC Class Codes: C08B 31/08 : Ethers
• CPC Class Codes: C08B 31/10 : Alkyl or cycloalkyl ethers
• CPC Class Codes: C08B 31/12 : having alkyl or cycloalkyl radicals substituted by heteroatoms, e.g. hydroxyalkyl or carboxyalkyl starch
• CPC Class Codes: C08B 31/16 : Ether-esters
• CPC Class Codes: C08B 31/18 : Oxidised starch
• CPC Class Codes: C08B 33/02 : Esters
• CPC Class Codes: C08B 33/04 : Ethers
• CPC Class Codes: C08B 33/06 : Ether-esters
• CPC Class Codes: C08B 35/02 : Esters
• CPC Class Codes: C08B 35/04 : Ethers
• CPC Class Codes: C08B 35/06 : Ether-esters
• CPC Class Codes: C08L 3/04 : Starch derivatives , e.g. crosslinked derivatives
• CPC Class Codes: C08L 3/18 : Ethers
• CPC Class Codes: C08L 89/06 : derived from leather or skin , e.g. gelatin
• CPC Class Codes: Y10T 428/2982 : Particulate matter [e.g., sphere, flake, etc.]

Abstract

A modified starch material for biocompatible hemostasis, biocompatible adhesion prevention, tissue healing promotion, absorbable surgical wound sealing and tissue bonding, when applied as a biocompatible modified starch to the tissue of animals. The modified starch material produces hemostasis, reduces bleeding of the wound, extravasation of blood and tissue exudation, preserves the wound surface or the wound in relative wetness or dryness, inhibits the growth of bacteria and inflammatory response, minimizes tissue inflammation, and relieves patient pain. Any excess modified starch not involved in hemostatic activity is readily dissolved and rinsed away through saline irrigation during operation. After treatment of surgical wounds, combat wounds, trauma and emergency wounds, the modified starch hemostatic material is rapidly absorbed by the body without the complications associated with gauze and bandage removal.

Claims

1. A method of treating a tissue of an animal, comprising a step of applying a biocompatible modified starch to the tissue of the animal, wherein the modified starch has a molecular weight 15,000 daltons or more and a grain diameter of 1 to 1000 μ

m.

2. The method, as recited in claim 1, further comprising a step of applying the biocompatible modified starch to a wound surface of the tissue for hemostasis.

3. The method, as recited in claim 1, further comprising a step of applying the biocompatible modified starch to a wound surface of the tissue for adhesion prevention and promoting tissue healing.

4. The method, as recited in claim 1, further comprising a step of applying the biocompatible modified starch to a wound surface of the tissue to prevent bleeding and fluid exudation from the tissue.

5. The method, as recited in claim 2, further comprising a step of degrading the biocompatible modified starch with amylase and carbohydrase in the wound surface and transforming into monosaccharides for absorption.

6. The method, as recited in claim 2, further comprising a step of promoting bacteriostatic and anti-inflammatory effects on the wound surface.

7. The method, as recited in claim 2, wherein the modified starch has water absorbency capacity of 1 to 100 times.

8. The method, as recited in claim 1, wherein the animal is selected from a group consisting of mammal, birds, and reptile.

9. The method, as recited in claim 1, wherein the tissue of the animal is a tissue of skin surface or internal organs, wherein the biocompatible modified starch is able to be used for hemostasis, adhesion prevention, tissue healing promotion, wound sealing, and wounded tissue bonding in surgical operation and trauma treatment including surgical treatment under laryngoscope, endoscope, and laparoscope.

10. The method, as recited in claim 2, wherein said modified starch is a synthetic modified starch product made into hemostatic power form, hemostatic spherical form, or hemostatic aerosol form.

11. The method, as recited in claim 1, further comprising a step of:

making the modified starch into a modified starch product by particle agglomerating and pellet processing, wherein the modified starch product is in form of hemostatic powder which has starch grains with grain diameter of 10˜

1000 μ

m containing at least 95% starch grains with a diameter of 30˜

500 μ

m in total, to provide effects of hemostasis, adhesion prevention, tissue healing promotion, sealing, adhesive plugging, and bonding to a bleeding wound surface.

12. The method, as recited in claim 1, further comprising the steps of:

applying the modified starch to a bleeding wound surface;

degrading the modified starch with amylase and carbohydrase in the bleeding wound surface, further transforming the modified starch into monosaccharides in the body;

allowing the modified starch to be absorbed by the body;

allowing the modified starch to promote bacteriostatic and anti-inflammatory effect on the bleeding wound surface; and

allowing the modified starch to dissolve or suspend in water after contacting with the water so as to irrigate the remaining excess modified starch after hemostasis achieved.

13. The method, as recited in claim 11, wherein the tissue of the animal is a tissue of skin surface or internal organs, wherein said biocompatible modified starch is able to be used for hemostasis, adhesion prevention, tissue healing promotion, wound sealing, and wounded tissue bonding in surgical operation and trauma treatment including the surgical treatment under laryngoscope, endoscope, and laparoscope.

14. The method, as recited in claim 12, wherein the biocompatible modified starch is hemostatic powder having hemostatic grains with a grain diameter of 10˜

1000 μ

m.

15. The method, as recited in claim 2, wherein the biocompatible modified starch is a synthetic modified starch hemostatic product made into hemostatic sponge, hemostatic foam, hemostatic film or hemostatic plaster in form of columnar, sheet, massive, flocculent, and membranous.

16. The method, as recited in claim 2, wherein the biocompatible modified starch is a synthetic modified starch hemostatic product, which is a hemostatic sponge, wherein the modified starch comprises an etherified starch which comprises at least one of carboxymethyl starch, hydroxyethyl starch and cationic starch.

17. The method, as recited in claim 2, wherein the biocompatible modified starch is a synthetic modified starch hemostatic product, which a hemostatic sponge, wherein the modified starch comprises a cross-linked starch which comprises at least a cross-linked carboxymethyl starch.

18. The method, as recited in claim 2, wherein the biocompatible modified starch is a synthetic modified starch hemostatic product, which is a hemostatic sponge, wherein the modified starch comprises a composite modified starch which comprises at least a pre-gelatinized hydroxypropyl distarch phosphate.

19. The method, as recited in claim 2, wherein the biocompatible modified starch is a synthetic modified starch hemostatic product, which is a hemostatic film, wherein the modified starch comprises at least one of a carboxymethyl starch, a hydroxyethyl starch, a cationic starch, a cross-linked carboxymethyl starch, a pre-gelatinized hydroxypropyl distarch phosphate, and a grafting starch.

20. The method, as recited in claim 1, wherein the biocompatible modified starch is a modified starch hemostatic product produced by the steps of:

(a) dissolving or swelling the modified starch into modified starch solution or suspension with liquid; and

(b) making the modified starch hemostatic product by vacuum freeze drying or vacuum drying the modified starch solution or suspension;

wherein the modified starch hemostatic product is in form of hemostatic sponge, hemostatic film, and hemostatic plaster and the bleeding wound surface is a wound surface of skin surface or internal organs, wherein the modified starch is able to be used for hemostasis, adhesion prevention, tissue healing promotion, wound sealing, and wounded tissue bonding in surgical operation and trauma treatment including the surgical treatment under laryngoscope, endoscope, and laparoscope.

21. The method, as recited in claim 20, wherein the modified starch is mixed, diluted and vacuum freeze dried with at least a material selected from the group consisting of biocompatible gelatin and collagen to produce a composite modified starch hemostatic material.

22. The method, as recited in claim 20, wherein the modified starch is mixed, diluted and vacuum freeze dried with at least a material selected from the group consisting of blood coagulation factor, fibrin, calcium agent, protamine, polypeptide, peptide, and amino acid to produce a modified starch hemostatic material that contains coagulant.

23. The method, as recited in claim 20, wherein said modified starch hemostatic product is made by a process comprising the steps of mixing, diluting and vacuum freeze drying a modified starch with at least a material selected from the group consisting of glycerol, kaolin, sorbitol, ethanol, ammonia, and polyethylene glycol to produce a modified starch hemostatic material that contains plasticizing agent.

24. The method, as recited in claim 20, wherein the modified starch is mixed, diluted and vacuum freeze dried with at least a material selected from the group consisting of biocompatible oxidized cellulose, carboxymethyl cellulose, chitosan, hyaluronic acid, and sodium alginate to produce a composite modified starch hemostatic material.

48. A preparation method of a biocompatible modified starch for treating a tissue of an animal as claimed in claim 1, wherein the method comprises the steps of:

(a) adding a starch material into a boiler under 40˜

50°

C.; and

(b) adding a distilled water, and making a finished product of modified starch material by agglomeration and pelletion;

wherein the modified starch material has a molecular weight of 15,000 daltons or more, and a grain diameter of 1˜

1000 μ

m containing at least 95% starch grains with a diameter of 30˜

500 μ

m in total;

wherein the modified starch provides the effects of hemostasis, preventing adhesion, promoting tissue healing, sealing, plugging, and adhering to a bleeding wound surface, and a bacteriostatic and anti-inflammatory effect to the bleeding wound surface, wherein the bleeding wound surface is a wound surface of skin surface or internal organs, wherein the modified starch is able to be used for hemostasis, adhesion prevention, tissue healing promotion, wound sealing, and wounded tissue bonding in surgical operation and trauma treatment including the surgical treatment under laryngoscope, endoscope, and laparoscope.

49. The method, as recited in claim 48, wherein the biocompatible starch material is a carboxymethyl starch material, a finished product of the modified starch material is a carboxymethyl starch (66#) whose suspension of 6.67% has a viscosity not lower than 30 mPa·

s under 37°

C., and an adhesion Work Index of the modified starch at maximum water absorption under room temperature exceeds 40 g·

sec (100% saturation).

50. The method, as recited in claim 48, wherein the starch material is a hydroxyethyl starch material, a finished product of the modified starch material is hydroxyethyl starch material (88#), and adhesion Work Index of the modified starch at maximum water absorption under room temperature exceeds 60 g·

sec (100% saturation).

51. The method, as recited in claim 48, wherein the starch material is a cross-linked carboxymethyl starch material, a finished product of the modified starch material is cross-linked carboxymethyl starch whose suspension of 6.67% has viscosity not lower than 30 mPa·

s under 37°

C., and adhesion work index of the modified starch at maximum water absorption under room temperature exceeds 40 g·

sec (100% saturation).

52. A preparation method of a modified starch for treating a tissue of an animal as claimed in claim 1, comprising the steps of:

a) providing a biocompatible modified starch material having a molecular weight of 15,000 daltons or more and a grain diameter of 1˜

1000 μ

m;

b) adding water, agitating, and inducing sufficient swelling of the starch grains and dispersing them into water to form uniform emulsion;

c) freeze for 22 hours under −

40°

C.;

d) placing into a refrigerant drying apparatus, freeze drying for 20 hours under −

40˜

−

50°

C. and vacuum less than 20 Pa; and

e) obtaining a modified starch hemostatic sponge/foam;

wherein the modified starch provides effects of hemostasis, preventing adhesion, promoting tissue healing, sealing, adhesive plugging, and adhering, to a bleeding wound surface, and a bacteriostatic and anti-inflammatory effect to the bleeding wound surface.

53. The method, as recited in claim 52, further comprising the steps of adding a forming agent into the modified starch material of the step (a), mixing uniformly, and obtaining a modified starch sponge/foam containing the forming agent, which is applied to the bleeding wound surface of skin surface or internal organs, wherein the modified starch provides the effects of hemostasis, adhesion prevention, tissue healing promotion, wound sealing and wounded tissue bonding, wherein the forming agent comprises at least a material selected from a group of gelatin, collagen, oxidized cellulose, carboxymethyl cellulose, chitosan, hyaluronic acid, sodium alginate, glycerol, kaolin, sorbitol, ethanol, ammonia, and polyethylene glycol.

25. A method of producing a biocompatible modified starch, comprising steps of:

(a) modifying a biocompatible starch; and

(b) producing a modified starch, wherein the modified starch has a molecular weight 15,000 daltons or more and a grain diameter of 1˜

1000 μ

m.

26. The method, as recited in claim 25, wherein the modified starch provides effects of hemostasis, preventing postoperative adhesions, promoting tissue healing, sealing blood vessels, sealing wounds, and adhering wounds to a bleeding wound surface, and a bacteriostatic and anti-inflammatory effect to the bleeding wound surface, wherein the bleeding wound surface is a tissue of skin surface or internal organs, wherein the modified starch is able to be used for hemostasis, adhesion prevention, tissue healing promotion, wound sealing, and wounded tissue bonding in surgical operations and trauma treatments including the surgical treatment via laryngoscope, endoscope, and laparoscope.

27. The method, as recited in claim 25, wherein the molecular weight of the modified starch is 15,000˜

2,000,000 daltons,

28. The method, as recited in claim 25, wherein the modified starch has a water absorbency of 1˜

500 times its particle weight.

29. The method, as recited in claim 25, wherein the modified starch is a modified starch containing hydrophilic group.

30. The method, as recited in claim 25, wherein the modified starch dissolves or swells in water and forms adhesive gel or adhesive liquid.

31. The method, as recited in claim 27, wherein the modifying process of the biocompatible starch is selected from a group consisting of physical modifying process, chemical modifying process, enzymatical modifying process, and natural modifying process.

32. The method, as recited in claim 31, wherein the physical modifying process includes irradiating, mechanical and damp-heat treatments.

33. The method, as recited in claim 31, wherein the chemical modifying process includes at least a chemical modifying treatment with a chemical reagent, which comprises a process selected from a group consisting of acidolysis, oxidation, esterification, etherification, cross-linking, and grafting modifying treatments.

34. The method, as recited in claim 27, wherein the modified starch comprises at least one of a pre-gelatinized starch, an acid modified starch, a dextrin, an oxidized starch, an esterified starch, an etherified starch, a grafting starch, a cross-linked starch, and a composite modified starch.

35. The method, as recited in claim 34, wherein a preparation process of the pre-gelatinized starch is modified by a dry process, including extrusion process and roller drying process.

36. The method, as recited in claim 34, wherein a preparation process of the pre-gelatinized starch is modified by a wet process, including spray drying process.

37. The method, as recited in claim 34, wherein the etherified starch comprises at least one of a carboxymethyl starch, a hydroxyethyl starch, and a cationic starch.

38. The method, as recited in claim 34, wherein the esterified starch comprises a hydroxypropyl distarch phosphate.

39. The method, as recited in claim 34, wherein the cross-linked starch comprises at least a cross-linked carboxymethyl starch.

40. The method, as recited in claim 34, wherein the grafting starch comprises at least a crylic acid-carboxymethyl starch grafting copolymer and a propylene ester-carboxymethyl starch grafting copolymer, wherein the grafting starch has a molecular weight of 50,000˜

2,000,000 daltons.

41. The method, as recited in claim 34, wherein the esterified starch comprises at least a hydroxypropyl distarch phosphate, wherein the cross-linked starch comprises at least a cross-linked carboxymethyl starch, wherein the grafting starch comprises at least a crylic acid-carboxymethyl starch grafting copolymer and a propylene ester-carboxymethyl starch grafting copolymer, wherein the modified starch has a volume of water absorbency not lower than 1 time its own particle weight.

42. The method, as recited in claim 34, wherein the modified starch has a volume of water absorbency not lower than 1 time its own particles weight.

43. The method, as recited in claim 41, wherein the modified starch has a water absorbency of 2˜

500 times its own particle weight.

44. The method, as recited in claim 33, wherein the step (a) comprises a step of making a pre-gelatinized hydroxypropyl distarch phosphate into a composite modified starch hemostatic material.

45. The method, as recited in claim 42, wherein the step (a) comprises a step of making a pre-gelatinized hydroxypropyl distarch phosphate into a composite modified starch hemostatic material, wherein the modified starch has a water absorbency of 2˜

50 times its particle weight.

46. The method, as recited in claim 33, wherein the step (a) comprises a step of grafting a carboxymethyl starch with a crylic acid and a propylene ester to make grafting starch hemostatic materials of crylic acid-carboxymethyl starch grafting copolymer and propylene ester-carboxymethyl starch grafting copolymer.

47. The method, as recited in claim 42, wherein the step (a) comprises a step of grafting a carboxymethyl starch with a crylic acid and a propylene ester to make a grafting starch hemostatic materials of crylic acid-carboxymethyl starch grafting copolymer and propylene ester-carboxymethyl starch grafting copolymer, wherein the modified starch has a water absorbency of 20˜

500 times its particle weight.