HAEMOSTATIC MATERIAL

Abstract

The present invention relates to a haemostatic material comprising a haemostat agent and a bioadhesive agent. Such a haemostatic material is useful, for example, in effectively controlling bleeding with a reduced compression period compared to the TCCC guidance of a minimum of three minutes compression using a haemostatic bandage.

Claims

1. A haemostatic material comprising a haemostat agent and a bioadhesive agent.

2. A haemostatic material as claimed in claim 1, wherein the haemostat agent is selected from the list consisting of: oxidised regenerated cellulose, kaolin, gelatin, calcium ions, zeolite, collagen, chitosan and chitosan derivatives.

3. A haemostatic material as claimed in claim 1, wherein the haemostat agent is a chitosan salt.

4. A haemostatic material as claimed in claim 3, wherein the chitosan salt comprises one or more chitosan salts selected from: chitosan acetate, chitosan lactate, chitosan succinate, chitosan malate, chitosan sulphate and chitosan acrylate.

5. A haemostatic material as claimed in claim 4, wherein the chitosan salt is chitosan succinate.

6. A haemostatic material as claimed in claim 1, wherein haemostat agent constitutes at least 20% by weight of the haemostatic material.

7. A haemostatic material as claimed in claim 6, wherein the haemostat agent constitutes at least 80% by weight of the haemostatic material.

8. A haemostatic material as claimed in claim 5, wherein the haemostat agent constitutes from 20 to 99% by weight of the haemostatic material.

9. A haemostatic material as claimed in claim 8, wherein the haemostat agent constitutes from 45 to 95% by weight of the haemostatic material.

10. A haemostatic material as claimed in claim 1, wherein the haemostat agent is granular, short fibres, sponges, fabrics, films, powders, liquid, gels or liquid coating.

11. A haemostatic material as claimed in claim 10, wherein the short fibres are no more than 7.5 mm in length.

12. A haemostatic material as claimed in claim 11, wherein the short fibres are no more than 5 mm in length.

13. A haemostatic material as claimed in claim 1, wherein the haemostat agent has a pH of from about 3.5 to about 8.0.

14. A haemostatic material as claimed in claim 1, wherein the adhesion of the material to dry surfaces has a peel force of 0.05 N per 25 mm or below and the adhesion to wet/moist surfaces has a peel force of 0.25 N per 25 mm or above.

15. A haemostatic material as claimed in claim 14, wherein the adhesion to a wet/moist surface has a peel force of 0.7 N per 25 mm or above.

16. A haemostatic material as claimed in claim 15, wherein the adhesion to a wet/moist surface has a peel force of 1.0 N per 25 mm or above.

17. A haemostatic material as claimed in claim 1, wherein the adhesion of the material to wet/moist surfaces has a peel force in the range 0.6 to 2.0 N per 25 mm.

18. A haemostatic material as claimed in claim 1, wherein the bioadhesive agent constitutes up to 90% by weight of the haemostatic material.

19. A haemostatic material as claimed in claim 18, wherein the bioadhesive agent constitutes up to 20% by weight of the haemostatic material.

20. A haemostatic material as claimed in claim 19, wherein the bioadhesive agent constitutes from 2 to 20% by weight of the haemostatic material.

21. A haemostatic material as claimed in claim 20, wherein the bioadhesive agent constitutes from 5 to 10% by weight of the haemostatic material.

22. A haemostatic material as claimed in claim 21, wherein the bioadhesvie agent constitutes from 7 to 8% by weight of the haemostatic material.

23. A haemostatic material as claimed in claim 1, wherein the bioadhesive agent is selected from the following, either alone or in combination: carbomers, polyvinyl alcohol, polyvinylpyrrolidone, 2-acrylamido-2-methylpropane sulfonic acid, an acrylic acid polymer having a molecular weight of at least 50000 g/mol cross-linked with divinyl glycol or the salts of polyacrylic acid cross-linked with divinyl glycol.

24. A haemostatic material as claimed in claim 23, wherein the bioadhesive agent comprises a homopolymer comprising a polymer of acylic acid cross-linked with allyl sucrose or allyl pentaerythritol; a copolymer comprising a polymer of acrylic acid and C10-C30 alkyl acrylate cross linked with allyl pentaerythritol; a carbomer homopolymer or copolymer comprising a block copolymer of polyethylene glycol and a long chain alkyl acid ester, or mixtures thereof.

25. A haemostatic material as claimed in claim 1, wherein the haemostat agent and the bioadhesive agent are present in a ratio of at least 3:1.

26. A haemostatic material as claimed in claim 25, wherein the haemostat agent and the bioadhesive agent are present in a ratio of at least 4:1.

27. A haemostatic material as claimed in claim 26, wherein the haemostat agent and the bioadhesive agent are present in a ratio of at least 9:1.

28. A haemostatic material as claimed in claim 1, wherein the bioadhesive agent is anionic and the haemostat agent is cationic.

29. A haemostatic material as claimed in claim 1, further comprising an inert material.

30. A haemostatic material as claimed in claim 29, wherein the inert material comprises one or more components selected from: non-haemostatic cellulose, non-haemostatic sand, non-haemostatic clay, non-haemostatic alginate, microcrystalline cellulose, guar gum, xanthan gum, non-haemostatic chitosan, non-haemostatic chitin, dextran, sucrose, lactose, pectin, carboxymethylcellulose, hydroethyl cellulose, ground corn meal, polyacrylic acid, barium sulphate, starch, or combinations of any two or more thereof.

31. A haemostatic material as claimed in claim 29, wherein the inert material constitutes up to about 95% by weight of the haemostatic material.

32. A haemostatic material as claimed in claim 29, wherein the inert material is in the form of granules, a powder, foam, fibres or a film.

33. A haemostatic material as claimed in claim 1, further comprising a medical surfactant.

34. A haemostatic material as claimed in claim 33, wherein the medical surfactant comprises one or more components selected from: block copolymers based on ethylene oxide and propylene oxide, glycerol, polyethylene glycol, propylene glycol, fatty acids, fatty acid salts, silicone based surfactants and emulsifiers.

35. A haemostatic material as claimed in claim 33, wherein the medical surfactant is a fatty acid selected from lauric acid and oleic acid.

36. A haemostatic material as claimed in claim 33, wherein the medical surfactant constitutes from about 0.001 to about 10% by weight of the haemostat agent.

37. A haemostatic material as claimed in claim 1, wherein the haemostat agent comprises particles that will not pass through a 200 mesh sieve.

38. A haemostatic material as claimed in claim 29, wherein the particle size of the inert material will be substantially equivalent to that of the haemostat agent.

39. A haemostatic material as claimed in claim 1 in dry powder, solution, foam or gel form.

40. A carrier material comprising a haemostatic material as claimed in claim 1 applied to the carrier material.

41. A carrier material as claimed in claim 40 in the form of a viscose non-woven material, a thin flexible substrate, a woven gauze, a film, a foam, or a sheet gel.

42. A carrier material as claimed in claim 40, wherein the carrier material is made from oxidised cellulose, gelatin, dextran, collagen, polycaprylactone, polylactide acid, polylactide-co-glycolide, polyglycolide, or chitin.

43. A method of haemostasis, the method comprising the steps of applying the haemostatic material as claimed in claim 1 to a physiological target site; and applying pressure to the haemostatic material.

44. A method as claimed in claim 43, wherein the pressure is applied for less than three minutes.

45. A haemostatic material as claimed in claim 1 for use in stemming blood flow from a physiological target site.

46. A method of manufacturing a haemostatic material, the method comprising the step of combining a haemostat agent with a bioadhesive agent.

47. A method as claimed in claim 44, wherein the method comprises the steps of: 1. dispensing a pre-determined weight of a haemostat agent and optionally an inert material into a mixing vessel; 2. dispensing a pre-determined weight of a bioadhesive agent into the mixing vessel containing the haemostat and optional inert material; and 3. mixing the haemostat agent and bioadhesive agent.

48. Use of a haemostatic material as claimed in claim 1 in reducing or stopping blood flow from a physiological target site.

49. (canceled)

50. A haemostatic material as claimed in claim 1, wherein the haemostat agent is selected from the list consisting of: oxidised regenerated cellulose, kaolin, gelatin, calcium ions, zeolite, collagen, chitosan and chitosan derivatives, and wherein the bioadhesive agent is present in an amount of from 2-20% by weight of the haemostatic material.

Description

[0061] Embodiments of the present invention will now be described further in the following non-limiting examples with reference to the accompanying drawings in which:

[0062] FIG. 1 is a graph displaying the peel force required to remove a haemostatic material from a wound versus time for compositions of the present invention and known devices;

[0063] FIG. 2 is a graph displaying the peel force required to remove a haemostatic material from a wound versus time for compositions of the present invention and comparative examples.

EXAMPLE 1

[0064] A 5 wt% bioadhesive agent (high molecular weight cross-linked polymers of acrylic acid (Carbopol® NF934)) was blended with a chitosan lactate/non-haemostatic chitosan blend. The mixture was double-coated onto viscose gauze at a coat weight of 40 gsm. This provided a haemostatic material referred to herein as ‘Described Invention’

EXAMPLE 2

[0065] A 10 wt% bioadhesive agent (high molecular weight cross-linked polymers of acrylic acid (Carbopol® NF934)) was blended with a chitosan lactate/non-haemostatic chitosan blend. The mixture was double-coated onto viscose gauze at a coat weight of 40 gsm.

[0066] The effectiveness of the haemostatic materials of Examples 1 and 2 was assessed in vivo and in vitro as described below.

In Vitro

[0067] An in vitro adhesion model was used to assess the ability of the haemostatic material to adhere to moist tissue. The model incorporated using the underside of pork belly. The pork belly was kept in cool conditions for 24 hours prior to testing (3° C.) to ensure all moisture was retained within the pork belly. Sample strips of the test articles were cut to 25 mm width. The test articles were applied to the pork belly and a 5 kg weight applied over the top. The adhesion to the moist pork belly was assessed at 1 min, 3 min and 20 min using a tensiometer.

[0068] The results presented in FIG. 1 show that the haemostatic material of the present invention has a significantly greater adhesion compared to the known devices. The dressings tested were Hemeon Chitogauze®, Celox® gauze and Quickclot® Combat Gauze®.

[0069] For a comparative analysis of the enhanced effect of haemostatic material of the present invention versus haemostat agents alone, further work was undertaken using oxidised regenerated cellulose with and without high molecular weight cross-linked polymers of acrylic acid and a gauze impregnated with kaolin with and without high molecular weight cross-linked polymers of acrylic acid.

[0070] Oxidised regenerated cellulose comprising 5 wt% of a high molecular weight cross-linked polymer of acrylic acid (Carbopol® NF980) is shown as Described Invention 1. A gauze impregnated with kaolin comprising 20 wt% of a high molecular weight cross-linked polymer of acrylic acid (Carbopol® NF980) is shown as Described Invention 2. Carrier 1 and Carrier 2 comprise oxidised regenerated cellulose and gauze impregnated with kaolin respectively. The results are shown in FIG. 2. As can be seen, the haemostatic materials of the present invention have a significantly greater adhesion to the tissue compared to the oxidised regenerated cellulose and gauze impregnated with kaolin.

In Vivo

[0071] To confirm the wet adhesion gave real advantages in compression time and provided evidence of efficacy with 1 minute compression the compositions of Examples 1 and 2 were tested in a porcine model using a 6 mm femoral artery sever model. A 6 mm sever was surgically made to the femoral artery of a porcine model. The artery was allowed to bleed out for a period of 45 seconds following which the haemostatic material was applied to the bleed site and pressure applied for a period of one minute. Following the compression period the wound was assessed for bleeding. If bleeding re-occurred, the haemostatic material was removed and a new sample re-applied to the bleed site followed by one minute pressure. Any re-bleeding after this point was classified as a fail.

[0072] The results demonstrated that 94% of the models treated obtained haemostasis within the protocol in the femoral artery model.

Adhesion

[0073] Further testing was conducted to assess the adhesion of the haemostatic material of the present invention to a dry tissue surface, compared to the above referenced tests for adhesion to a wet tissue surface. The haemostatic materials of Described Invention, Described Invention 1 and Described Invention 2 were tested in comparison to prior art devices including Hemeon Chitogauze®, Celox® gauze, Quickclot Combat Gauze® and oxidised regenerated cellulose. The peel force of each material was assessed on dry and wet tissue after time intervals of 1, 3 and 20 minutes. The results are shown in Table 1 below.

TABLE-US-00001 Peel force (N/25mm) Tissue Type 1 min 3 min 20 min Hemeon Chitogauze® Wet 0.021 0.018 0.019 Celox® Gauze Wet 0.12 0.09 0.078 Quickclot® Combat Gauze® Wet 0.019 0.021 0.019 Oxidised Regenerated cellulose Wet 0.14 0.174 0.192 Described Invention Wet 1.01 0.98 1.15 Described Invention 1 Wet 0.692 0.745 0.758 Described invention 2 Wet 1.2 1.25 1.38 Hemeon Chitogauze® Dry No adhesion No adhesion No adhesion Celox® gauze Dry No adhesion No adhesion No adhesion Quickclot® Combat Gauze® Dry No adhesion No adhesion No adhesion Oxidised Regenerated cellulose Dry No adhesion No adhesion No adhesion Described Invention Dry No adhesion No adhesion No adhesion Described Invention 1 Dry No adhesion No adhesion No adhesion Described Invention 2 Dry No adhesion No adhesion No adhesion

[0074] As can be seen in Table 1, the haemostatic materials of the present invention exhibited no adhesion to dry tissue and high adhesion to wet tissue at each of the three time intervals. The results show a higher wet adhesion of the haemostatic materials of the present invention as compared to the known devices.

[0075] 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.