Hemostatic composition

Abstract

A hemostatic composition for effecting hemostasis at a hemorrhaging site comprises a hemostatically effective amount of cationic substance and a base, wherein the base is in a form of an ointment, a cream, a gel, a foam or a paste, and wherein the cationic substance is substantially uniformly dispersed in the base. The method of preparing the hemostatic composition includes admixing an aqueous solution of a cationic substance and the base, and freeze-drying the mixture to remove substantially all of the water to yield a viscous water soluble composition of fine particles of cationic which is substantially uniformly dispersed throughout the base, and the method of its use to provide hemostasis to a hemorrhaging site of a mammal.

Description

REFERENCE TO RELATED APPLICATION

[0001] This application is a continuation in part of U.S. patent application Ser. No. 10/008,052, filed Nov. 13, 2001, the disclosure of which is incorporated herein by reference.

FIELD OF THE INVENTION

[0002] The invention relates to hemostatic compositions useful for surgical applications. More particularly, the invention relates to a hemostatic composition in an ointment, cream, gel, foam or paste form useful as a surgical hemostat.

BACKGROUND OF THE INVENTION

[0003] Puncture of blood vessels is a necessary stage in many of the minimally invasive approaches to diagnosis and treatment, including interventional radiology and cardiology. Therefore, a need to create hemostasis as rapidly as possible following the procedure becomes an important priority.

[0004] The cationic substance may be a high molecular weight cationic polyelectrolyte. Generally, the cationic polymer is derived from animals (sea life) or plants (fungi, polysaccharides), or synthesized by various processes.

[0005] Cationic substances suitable for hemostasis are generally available in two forms, i.e. dry powder or an aqueous solution. In a dry powder form, a cationic substance is used by tapping cationic particles out from a container onto a hemorrhaging site. The dry cationic substance is not easily handled and applied during surgery because it is difficult to quickly measure out the desired amount when a hemorrhaging site is discovered. Cationic substances used in aqueous solution have the disadvantage of diminishing the potency of the cationic substance by dilution. Further, aqueous cationic substances solutions are not stable due to the denaturation and autolysis of the cationic substance in solution. It is therefore an object of the present invention to provide a hemstatically effective, convenient, and storage stable form of cationic substance ideally suited for surgical use.

SUMMARY OF THE INVENTION

[0006] The present invention provides a hemostatic composition, which comprises a hemostatically effective cationic substance and a base, wherein the base is in a form selected from the group consisting of an ointment, a cream, a gel, a foam, and a paste, and wherein the cationic substance is substantially uniformly dispersed in the base.

[0007] Many hemostasis methods have been utilized or attempted, including suture-based devices, collagen plugs, pressure applying devices, and the like. The situation is complicated further by the use of anticoagulants in these procedures, which prolongs clotting times. Substances such as heparin, aspirin, coumadin, and other anticoagulants are used with regularity and affect the normal blood coagulation cascade. The use of cationic substances in flocculation and coagulation in non-medical situations such as water treatment, paper production, industrial sludge treatment, and the like has been effectively used in the past and is well documented. The method of action is by precipitating, coagulating or flocculating suspended particles which are negatively charged by virtue of using positively charged materials, which attract the oppositely charged ions.

[0008] It has been clearly demonstrated that the charge on blood cells and components (platelets, etc.) is negative. By using a positively charged biocompatible substance, it is possible to agglomerate these cells creating coagulation through a system other than by virtue of the normal clotting cascade. Innocuous polymers are positively charged (cationic substances) as the initiator of coagulation in clinical situations. Additionally, positive charges can be applied via iontophoretic methods using electrode pads and positively charged treatment sites to accomplish the same thing.

[0009] The use of a positive charge administered by either cationic substances or by iontophoretic means to quickly create a coagulation process and hemostasis until the normal clotting cascade can take over. This can occur even in the face of significant anticoagulation since the process is ionic and not effected by the anticoagulants, which operate on the normal blood cascade. This approach can be revolutionary in the after treatment of patients with minimally invasive or invasive procedures since rapid hemostasis and mobilization of the patient are desirable endpoints.

[0010] The cationic substance can be incorporated into many forms, such as woven and non-woven pads, fibers, gels, pastes, waxes, foams, sprays, liquids of varying viscosities, packings, membranes, sheets, and the like. Additionally, these forms can be incorporated and utilized with iontophoretic types of equipment that create a positive charge at the bleeding site to effect coagulation.

[0011] Utilizing colloidal chemistry for effecting coagulation ionically in suspensions or colloidal substance by providing cationic charges, has enormous value in the diagnosis and treatment of conditions such as cardiovascular disease, interventional radiological procedures, and the like. The cationic charge can be provided by a substance with a positively charged surface, or electronically by utilizing electrophoretic type equipment and electrode pads specifically designed to be disposable, conductive and sterile, designed to fit the required anatomical site. Many cationic substances are available, such as polymers, polysaccharides and starches, aluminum salts, magnesium salts, natural polymers such as chitosan, and the like.

[0012] The use of ionic charges to create hemostasis is a new and important process in the treatment of disease processes. This novel approach can be administered by applying sterile, biocompatible, positively charged materials directly in contact with the blood column, accompanied by pressure, or provided electronically by utilizing controlled direct current on the positive side with iontophoretic type approaches and specially constructed, disposable, sterile electrodes to the bleeding site

[0013] In accordance with purposes of the invention, as embodied and fully described herein, the invention comprises a hemostatic composition comprising a hemostatically effective amount of a cationic substance in a base in a form of an ointment, a cream, a gel a foam, or a paste. The cationic substance may be folded in as a powder or may be dissolved in biocompatible solutes and added mechanically as a solution. Preferably, a cationic substance powder is dissolved in a mixture of water and the base and the mixture is dried, preferably freeze-dried to remove the water leaving the particles of cationic substance substantially uniformly dispersed in the base.

[0014] The invention also comprises a process for preparing a hemostatic composition comprising the steps of admixing an aqueous solution of cationic substance and a base in a form of ointment, cream, gel, foam or paste, and freeze-drying the mixture to remove substantially all of the water to yield a viscous water soluble wax of cationic substance.

[0015] The invention further comprises a method for reducing bleeding at a hemorrhaging site by applying a cationic substance composition which comprises a hemostatically effective amount of cationic substance in a base in a form of ointment, cream, gel, foam or paste, to the hemorrhaging site of a mammal. The cationic substance may be applied in combination with a fibrous gauze material or by itself in a base in a form of ointment, cream, gel, foam or paste to the hemorrhaging site.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] Reference will now be made in detail to preferred embodiments of the invention.

[0017] The hemostatic cationic composition of the present invention provides convenient ready to use hemostatically effective amounts of a cationic substance for application to a hemorrhaging site. The cationic substance composition is substantially homogeneously dispersed throughout a base in a form of ointment, cream, gel, foam or paste, and remains storage stable until it is ready for use.

[0018] A ready-to-use form of ointment, cream, gel, foam or paste of the present invention is advantageous over aqueous solution forms of cationic substance which must be reconstituted from dry cationic substance powder prior to use. Additionally, an aqueous cationic substance solution has a low viscosity and a low potency due to its dilute nature. Further, aqueous solutions of cationic substance are frequently applied in conjunction with and absorbed on a coated paper, or saturated gauze dressing because of their low viscosity and potency. In contrast, the hemostatic cationic substance composition of the present invention has a viscosity and potency which is high enough to permit its hemostatically effective use by a surgeon by dipping of a gloved finger into a hemostatic cationic substance composition, removing portion of that composition, and placing the removed portion over a bleeding site.

[0019] The hemostatic cationic substance composition of the invention may also be used in conjunction with a gauze, cellulose, or collagen material by either coating such material as a substrate with the hemostatic composition and applying it to a hemorrhaging site or first applying the cationic substance composition to a hemorrhaging site and placing a cellulose, gauze or collagen on top of the hemostatic composition and applying pressure thereto.

[0020] The hemostatic composition of the present invention requires no pre-preparation; it is non-toxic and absorbable by a mammalian body. It can be supplied in a sterile convenient to use delivery system such as a tube, jar or containers. The hemostatic cationic substance composition is anti-microbial as well due to the nature of these cationic substances.

[0021] In accordance with the purposes of the invention, as embodied and fully described herein, the invention comprises a mixture of a base a base in a form of ointment, cream, gel, foam or paste and a hemostatically effective amount of a cationic substance.

[0022] The present invention preferably utilizes, but is not limited to, a 1:1 ratio blend of hemostatic cationic substance and a base in a form of ointment, cream, gel, foam or paste which possesses petrolatum-like qualities. While 1:1 is the preferred ratio, the hemostatic agent may be 30-90% by weight of the composition. This most preferred ratio of polyethylene glycols can be altered to a degree from the normal 1:1 ratio to give the composition with slightly firmer or softer feel depending on the ratio of the base in a form of ointment, cream, gel, foam or paste. When the cationic substance is incorporated into any of a base in a form of ointment, cream, gel, foam or paste, a hemostatic composition is produced which can be applied to a cut, bleeding wound, incision, to effect rapid hemostasis through the release of hemostatic cationic substance.

[0023] The source of cationic substance can be derived from animals (sea life) or plants (fungi, polysaccharides), or can be synthesized by various processes.

[0024] The most preferred method of preparing the paste is to mix the cationic substance and the base together with water using no less water than 10 times the weight of base. The water dissolves all the components and forms a homogeneous solution. The solution is then frozen and lyophilized under high vacuum to evaporate the water while in the frozen state. After the water is fully removed, the mixture is brought up to room temperature producing a soft, smooth, water free composition with cationic substance distributed uniformly throughout.

[0025] The hemostatic composition of the present invention can also be prepared by physically blending the dry cationic substance powder into the soft base in form of ointment, cream, gel, foam or paste and mixing well to uniformly distribute the cationic substance particles throughout the base.

[0026] In preferred embodiments the cationic substance composition of the invention is prepared by first admixing a hemostatic effective amount of cationic substance with water. The cationic substance is an aqueous solution as it is admixed with the base and must be freeze-dried to provide a smooth composition. Mixing of powdered cationic substance with the base will give a lumpy composition as will mixing an aqueous solution of cationic substance with the base and air drying. Freeze-drying the admixture of aqueous cationic substance and the base is required to yield very small particles of cationic substance homogeneously dispersed throughout the composition mixture without loss of activity.

[0027] The hemostatic composition of the present invention has a viscosity which is most desirable for producing a product which may be handled easily by a surgeon during surgical procedures where a hemostat is necessary. The viscosity achieved also permits easy dispensing of the composition from a tube by squeezing out the desired amount onto a gloved finger of the surgeon or on to a substrate such as a gelatin sponge, gauze or collagen material or for dispensing from a jar by dipping of a gloved finger therein.

[0028] In the above embodiments, the hemostatic agent is preferably a cationic polymer of glucosamine. The cationic biopolymer of glucosamine is provided in one or more of the following forms: poly-D-glucosamine; an acetate salt of poly-N-acetylglucosamine; an acetate salt of poly-D-glucosamine; poly-N-acetylglucosamine and poly-D-glucosamine; an acetate salt of poly-N-acetylglucosamine and poly-D-glucosamine; an acetate salt of poly-N-acetylglucosamine and an acetate salt of poly-D-glucosamine, and poly-N-acetylglucosamine and an acetate salt of poly-D-glucosamine. In forms including an acetate salt, the application surface is water soluble. Acidic environments other than an acetate salt, such as lactic acid, can also be incorporated as part of the biopolymer of glucosamine.

[0029] In a preferred form, the cationic biopolymer of glucosamine is derived from chitosan, which is a collective term applied to deacetylated chitins in various stages of deacetylation and depolymerization. Chitin is the structural polymer of the exo-skeleton of arthropods and cell walls of fungi, and is composed of poly-N-Acetyl glucosamine units. These are linked by Beta 1-4 glycosidic bonds into a linear polymer containing 2,000 to 3,000 units.

[0030] The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are therefore to be considered in all respects illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

Claims

1. A hemostatic composition comprising:

a hemostatically effective amount of hemostatic cationic substance; and

a base, wherein said hemostatic cationic substance is substantially uniformly dispersed in said base, and wherein said base is in a form selected from the group consisting of an ointment, a cream, a gel, a foam, and a paste.

2. The composition of claim 1, wherein the hemostatic cationic substance comprises a biopolymer of glucosamine,

3. The composition of claim 2, wherein the biopolymer of glucosamine is poly-N-acetylglucosamine.

4. The composition of claim 2, wherein the biopolymer of glucosamine is poly-D-glucosamine.

5. The composition of claim 2, wherein the biopolymer of glucosamine is an acetate salt of poly-N-acetylglucosamine.

6. The composition of claim 2, wherein the biopolymer of glucosamine is an acetate salt of poly-D-glucosamine.

7. The composition of claim 2, wherein the biopolymer of glucosamine is poly-N-acetylglucosamine and poly-D-glucosamine.

8. The composition of claim 2, wherein the biopolymer of glucosamine is an acetate salt of poly-N-acetylglucosamine and poly-D-glucosamine.

9. The composition of claim 2, wherein the biopolymer of glucosamine is an acetate salt of poly-N-acetylglucosamine and an acetate salt of poly-D-glucosamine.

10. The composition of claim 2, wherein the biopolymer of glucosamine is poly-N-acetylglucosamine and an acetate salt of poly-D-glucosamine.

11. The composition of claim 1, wherein said base is water-soluble.

12. The composition of claim 1 further includes an anti-microbial material.

13. A method for making a hemostatic composition comprising:

mixing a hemostatically effective amount of hemostatic cationic substance and a base, wherein said base is in a form selected from the group consisting of an ointment, a cream, a gel, a foam, and a paste.

14. The method of claim 13, wherein the hemostatic cationic substance comprises a biopolymer of glucosamine,

15. The method of claim 14, wherein the biopolymer of glucosamine is poly-N-acetylglucosamine.

16. The method of claim 14, wherein the biopolymer of glucosamine is poly-D-glucosamine.

17. The method of claim 14, wherein the biopolymer of glucosamine is an acetate salt of poly-N-acetylglucosamine.

18. The method of claim 14, wherein the biopolymer of glucosamine is an acetate salt of poly-D-glucosamine.

19. The method of claim 14, wherein the biopolymer of glucosamine is poly-N-acetylglucosamine and poly-D-glucosamine.

20. The method of claim 14, wherein the biopolymer of glucosamine is an acetate salt of poly-N-acetylglucosamine and poly-D-glucosamine.

21. The method of claim 14, wherein the biopolymer of glucosamine is an acetate salt of poly-N-acetylglucosamine and an acetate salt of poly-D-glucosamine.

22. The method of claim 14, wherein the biopolymer of glucosamine is poly-N-acetylglucosamine and an acetate salt of poly-D-glucosamine.

23. The method of claim 13, wherein said base is water-soluble.

24. The method of claim 13 further includes a step of mixing an anti-microbial material in said composition.

25. A method for effecting hemostatic composition at a hemorrhaging site in a mammal comprising:

A). forming a hemostatic composition by mixing a hemostatically effective amount of hemostatic cationic substances and a base, wherein said base is in a form selected from the group consisting of an ointment, a cream, a gel, a foam, and a paste; and

B). applying a hemostatically effective amount of said hemostatic composition to the hemorrhaging site of the mammal.

26. The method of claim 25 further includes maintaining pressure for a predetermined time on the hemorrhaging site after applying said hemostatic composition to the hemorrhaging site of the mammal.

27. The method of claim 25, wherein the hemostatic cationic substance comprises a biopolymer of glucosamine,

28. The method of claim 27, wherein the biopolymer of glucosamine is poly-N-acetylglucosamine.

29. The method of claim 27, wherein the biopolymer of glucosamine is poly-D-glucosamine.

30. The method of claim 27, wherein the biopolymer of glucosamine is an acetate salt of poly-N-acetylglucosamine.

31. The method of claim 27, wherein the biopolymer of glucosamine is an acetate salt of poly-D-glucosamine.

32. The method of claim 27, wherein the biopolymer of glucosamine is poly-N-acetylglucosamine and poly-D-glucosamine.

33. The method of claim 27, wherein the biopolymer of glucosamine is an acetate salt of poly-N-acetylglucosamine and poly-D-glucosamine.

34. The method of claim 27, wherein the biopolymer of glucosamine is an acetate salt of poly-N-acetylglucosamine and an acetate salt of poly-D-glucosamine.

35. The method of claim 27, wherein the biopolymer of glucosamine is poly-N-acetylglucosamine and an acetate salt of poly-D-glucosamine.