Degradable haemostat composition

Abstract

In one aspect, the present invention includes a haemostat composition that has been washed with an alkali solution to reduce the presence of endotoxins, and which is able to safely gradually and fully degrade in a human or animal body within about 30 days and so can be utilised by physicians to stem a flow of blood and promote healing both after as well as during surgical procedures.

Claims

1. A haemostat composition comprising a chitosan, chitosan salt or chitosan derivative and a physiologically acceptable acid, wherein the physiologically acceptable acid is present in an amount of between about 20% and about 70% by weight of the haemostat composition, wherein the chitosan, chitosan salt or chitosan derivative is coated by the acid, wherein the haemostat composition is in a non-fibrous form, is able to fully degrade in a human or animal body within about 30 days, and the chitosan, chitosan salt or chitosan derivative has been washed with an alkali solution prior to coating with the acid for a period of longer than about 12 hours to reduce the presence of endotoxins; wherein the alkali solution has a concentration of 0.02 M to 0.2M.

2. The haemostat composition according to claim 1, wherein the haemostat composition is in the form of granules, powder, a sheet, a foam, a freeze dried foam, a compressed foam, a film, a perforated film, beads, a gel, a hydrogel sheets and amorphous hydrogel, or a laminate, or a combination of any two or more thereof.

3. The haemostat composition according to claim 1, wherein the haemostat composition is still present in the human or animal body after about 24 hours.

4. The haemostat composition according to claim 3, wherein complete degradation of the haemostat composition occurs after more than about 4 days but less than about 30 days.

5. The haemostat composition according to claim 4, wherein complete degradation of the haemostat composition occurs after more than about 7 days but less than about 30 days.

6. The haemostat composition according to claim 1, wherein the physiologically acceptable acid is present in an amount of between about 30% and about 60% by weight of the haemostat composition.

7. The haemostat composition according to claim 6, wherein the physiologically acceptable acid is present in an amount of between about 35% and about 55% by weight of the haemostat composition.

8. The haemostat composition according to claim 1, wherein the physiologically acceptable acid comprises an organic acid and/or an inorganic acid.

9. The haemostat composition according to claim 8, wherein the organic acid comprises a carboxylic acid.

10. The haemostat composition according to claim 9, wherein the carboxylic acid is selected from formic acid, acetic acid, ascorbic acid, halogen acetic acids, propanoic acid, propenoic acid, lactic acid, succinic acid, acrylic acid, glyoxylic acid, pyruvic acid or a hydroxy propionic/butanoic acid, or combinations of any two or more thereof.

11. The haemostat composition according to claim 10, wherein the carboxylic acid is selected from lactic, acetic and succinic acids, or combinations of any two or more thereof.

12. The haemostat composition according to claim 11, wherein the carboxylic acid is lactic acid.

13. The haemostat composition according to claim 8, wherein the inorganic acid comprises one or more of hydrochloric acid and/or sulphuric acid.

14. The haemostat composition according to claim 1, wherein the haemostat composition comprises a chitosan salt.

15. The haemostat composition according to claim 14, wherein the chitosan salt comprises one or more salts selected from chitosan acetate, chitosan lactate, chitosan succinate, chitosan malate, chitosan acrylate, chitosan formate, chitosan ascorbate, chitosan fluoroacetate, chitosan chloroacetate, chitosan propanoate, chitosan glyoxylate, chitosan pyruvate, chitosan sulphate, or chitosan chloride.

16. The haemostat composition according to claim 15, wherein the chitosan salt comprises chitosan lactate.

17. The haemostat composition according to claim 1, wherein the haemostat composition comprises a chitosan salt, the physiologically acceptable acid is a carboxylic acid and is present in an amount of between about 45-60% by weight of the haemostat composition, and the haemostat composition is in the form of granules or powder.

18. The haemostat composition according to claim 1, wherein the haemostat composition is made without subjecting the composition to any heat treatment after the composition has been dried.

19. The haemostat composition according to claim 1, wherein a molecular weight of the chitosan used for the preparation of the haemostat composition is less than about 500,000.

20. The haemostat composition according to claim 1, wherein a viscosity of the chitosan used for the preparation of the haemostat composition is from about 40 to about 200 cps when measured at 20 C.

21. The haemostat composition according to claim 1, wherein the haemostat composition is sterilised.

22. The haemostat composition according to claim 1, further comprising one or more components selected from pharmaceutical agents; wetting agents; colouring agents; processing aids; bulking agents; absorbent polymers; antimicrobial agents; growth factors; cytokines; agents which absorb agents which delay healing; calcium; vitamin K; fibrinogen; thrombin; factor VII; factor VIII; clays; oxidised regenerated cellulose; gelatine; and/or collagen.

23. A method of absorbing fluid discharged from a physiological target site, or of stemming a flow of a fluid discharged from a physiological target site, comprising applying to the physiological target site the haemostat according to claim 1.

24. The haemostat composition according to claim 1, wherein the haemostat composition is sterilised prior to being packaged.

25. The haemostat composition according to claim 1, wherein the chitosan derivative is a reaction product of chitosan with one or more compounds selected from the group consisting of carboxy methyl chitosan, hydroxyl butyl chitin, N-acyl chitosan, O-acyl chitosan, N-alkyl chitosan, O-alkyl chitosan, N-alkylidene chitosan, O-sulfonyl chitosan, sulfated chitosan, phosphorylated chitosan, nitrated chitosan, alkalichitin, alkalichitosan, and metal chelates.

Description

DETAILED DESCRIPTION

(1) The invention will now be described further by way of example with reference to the following examples which are intended to be illustrative only and in no way limiting upon the scope of the invention.

EXAMPLES

Method

(2) The total absorbency of the haemostat composition of the invention is determined using simulated wound fluid, serum and lysozyme solution. This is undertaken by determining the maximum absorbency of the materials by slowly adding fluid to the materials until no more can be absorbed. The amount of fluid absorbed is calculated from the wet weight minus the dry weight.

(3) Using the total absorbency volume for the material to be tested, this volume of lysozyme solution, simulated wound fluid or serum is decanted into a clean sealable beaker.

(4) The haemostat composition is added into the solution (the solution volume being greater than the maximum absorbency of the haemostat composition), ensuring that the weight of product is not greater than the absorbency potential for the volume of fluid within the beaker.

(5) The haemostat composition and solution are sealed and incubated at 37 C. (i.e. body temperature) for up to 30 days.

(6) At each time point the solution is visually assessed to determine whether and to what degree the haemostat composition has degraded.

(7) It is to be noted that at maximum absorbency at day 1, the degradation time is quicker than if the same volume of solution is applied gradually over a 5 day period.

(8) The haemostat composition is considered to have completely degraded if the viscosity of the lysozyme solution, simulated wound fluid or serum falls below 10 cps as measured at 20 C. on a Brookfield viscometer, measured by setting the viscometer to spindle 62 and setting the spindle speed to 60 rpm, or if the fluid in the beaker becomes optically clear with no particles or insoluble matter visible to the human eye.

(9) The degradation data after 1 day and 5 days is provided in Tables 1 and 2.

(10) TABLE-US-00001 TABLE 1 Test Data at maximum absorbency at day 1 Testing/Examples Days to full degradation Sample SWF Lysozyme soln Hemcon gauze >30 days >30 days CG 1600 chitosan >30 days >30 days Carboxymethylated chitosan >30 days >30 days Chitosan/Viscose/Acid blend >30 days >30 days Celox (chitosan salt) >30 days >30 days Celox gauze >30 days >30 days Chitosan granules with 20% Acid >30 days >30 days Chitosan granules with 55% Acid .sup.1 day .sup.1 day

(11) TABLE-US-00002 TABLE 2 Test Data at maximum absorbency at day 5 (gradually added fluid over 5 days) Testing/Examples Days to full degradation Sample SWF Lysozyme soln Hemcon gauze >30 days >30 days CG 1600 chitosan >30 days >30 days Carboxymethylated chitosan >30 days >30 days Chitosan/Viscose/Acid blend >30 days >30 days Celox (chitosan salt) >30 days >30 days Celox gauze >30 days >30 days Chitosan granules with 20% Acid >30 days >30 days Chitosan granules with 55% Acid .sup.5 day .sup.5 day

(12) It can therefore be seen that the haemostat compositions according to the invention degrade effectively over a desired period of between 1 and 30 days in conditions designed to replicate those that would be encountered in the human or animal body, and would be able to safely remain in the human or animal body post-surgery to aid in reducing and preventing incidences of re-bleeding and promoting healing, before completely degrading and being excreted from the body naturally.

(13) It is of course to be understood that the present invention is not intended to be restricted to the foregoing examples which are described by way of example only.