Wound covering with haemostatic action and the method of its creation

Abstract

According to some aspects of the invention a method for creation of a wound covering with haemostatic action includes: applying to an open wound a cell structure (grid)-forming water-soluble haemostatic composition designated as a Hemoblok consisting of a polyacrylic matrix as an active ingredient, where the matrix includes one or more polymeric carboxylic acid of a predetermined average molecular weight range, and a bactericidal agent; creating by Hemoblok on a wound surface a structure clot formation with blood plasma proteins, including albumin; creating by Hemoblok on the wound, a covering containing albumin molecules in cells of a polyacrylic structure matrix (grid), which is a primary organizer of sustainable grid structure clot film; further supplying of Hemoblok on an open wound surface to form a multilayered solid grid structure film; terminating of Hemoblok supply on a wound surface with following gradual replacement of a surface structure hemoblok-protein by fibrin.

Claims

1. A method for creation of a wound covering with haemostatic action comprising the steps of: applying to an open wound a cell structure, grid-forming water-soluble haemostatic composition designated as a Hemoblok and consisting of a polyacrylic matrix as an active ingredient, where said matrix comprising at least one polymeric carboxylic acid of a predetermined average molecular weight range, and a bactericidal agent; creating by Hemoblok on a wound surface of the open wound a structure clot formation with the blood plasma proteins, including albumin; creating by Hemoblok on the wound surface a covering containing albumin molecules in cells of a polyacrylic structure matrix grid, which is a primary organizer of sustainable grid structure clot film; further supplying of Hemoblok on the wound surface to form a multilayered solid grid structure film; and terminating of Hemoblok supply on the wound surface followed by gradual replacement of a surface structure hemoblok-protein with fibrin.

2. The method of claim 1, wherein said polyacrylic structure matrix serves as a primary organizer of stable film on the surface of the wound and is kept therein by weak interaction of polyacrylate negatively charged ions (anions polyacrylate) with positively charged proteins' functional groups.

3. The method of claim 2, wherein further silver ions are restored by protein functional groups to form a stable complex wherein polyacrylate anions form a strong communication with the positively charged proteins' functional groups and provide for protein agglutination to the wound surface and whereas at the threshold of albumin >10 mg/liter the Hemoblok introduction gives a quick hemostatic effect.

4. The method of claim 3, wherein created stable complex of the polyacrylic matrix structure forms multiple of micro-layers, creating a solid polyacrylate film on the surface of the wound.

5. The method of claim 4, wherein restored metallic and polyionic silver in a complex with proteins is a powerful bactericidal factor that provides the lack of suppuration during using the Hemoblok.

6. The method of claim 5, wherein further surface structure hemoblok-protein is gradually replaced by fibrin over time.

7. The method of claim 1, wherein the polyacrylic matrix provides plasmolysis during the first day and provides ulcers transformation by fibrin on the second day.

8. The method of claim 1, wherein said poly acrylic matrix structure comprises polyacrylate silver in very small amounts, comparable to natural blood coagulation factors and serves as the main organizer (plasticizer) of stable blood clot on the wound surface.

9. A wound covering, created by the method disclosed in claim 1, wherein said carboxylic acid is a polyacrylic acid having a structural formula [CH.sub.2—CHCO.sub.2H].sub.n, where n is at least 14.

10. The wound covering of claim 9, wherein said polyacrylic matrix comprises said polyacrylic acid where n is 30.

11. The wound covering of claim 9, wherein said bactericidal agent is selected from the group consisting of dissolved silver ions, oligomeric silver clusters, silver colloidal nanoparticles and any mixture thereof, wherein the said silver colloidal nanoparticles are of the size of from about 0.5 nm. to about 5 nm. and contains from about 1×10.sup.−5 moles per liter to about 1 mole per liter silver.

12. The wound covering of claim 9, wherein said grid-forming water-soluble haemostatic composition provides a protective layer that limits development of fibroblastic tissue and supports epithelialization.

13. The wound covering of claim 9, wherein n is from 14 to 1400.

14. The wound covering of claim 9, wherein n is from 14 to 140.

15. The method of claim 1, wherein said grid-forming water-soluble haemostatic composition designated as a Hemoblok may be additionally supplied with therapeutic substances incorporated in Hemoblok as soluble drugs to serve as antimicrobial agents, anti-inflammation agents, agents that resist apoptosis, or agents that preserve cellular functions.

16. The wound covering of claim 15, wherein the antimicrobial agents are selected from the group consisting of antibiotics and sulfonamides.

17. The wound covering of claim 15, wherein said anti-inflammation agents, the agents that resist apoptosis, and the agents that preserve cellular functions are selected from the group consisting of antioxidants and nutrients.

18. The wound covering of claim 17, wherein the Hemoblok haemostatic composition in form of a spray is used during surgery processing of the wound surfaces, including abdominal operations on parenchymal organs, and postoperative procedures such as bandaging, wound treatment, cuts and seams treatment.

19. The method of claim 1, wherein said grid-forming water-soluble haemostatic composition is applied on or in a woven or non-woven fabric, which is selected from the group consisting of gauze, paper, plastics, silicone polymers, resorbable materials, latexes and suitable derivatives of thereof.

20. The method of claim 19, wherein said resorbable materials is selected from the group consisting of proteinaceous materials, carbohydrate substances and resorbable suture materials.

21. The method of claim 1, wherein during mild bleeding on large wound surfaces such as burns, post-operative dressing the Hemoblok haemostatic composition is used as a spray.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIGS. 1 and 2 illustrate the rod-like particles of polyacrylic matrix which become centers of protein molecules binding and are adsorbed on the surface of the charged rod-like particles;

(2) FIG. 3 illustrates the structure of conglomerates of particles, which is formed as a hexagonal packing of polyacrylic matrix;

(3) FIG. 4 illustrates the complexes of polyacrylic matrix, which are joined together, forming a loop connected by straight portions;

(4) FIG. 5 illustrates proposed structure of the complexes scheme confirmed by electron microscopy;

(5) FIG. 6 illustrates a woven or non-woven fabric with applied haemostatic composition;

(6) FIG. 7 illustrates a syringe type device for haemostatic composition applying;

(7) FIG. 8-9 illustrate another device for haemostatic composition applying which is in the form of mechanical or pneumatic gun;

(8) FIG. 10 illustrates a visible anastomosis of aorta prior to the application Hemoblok;

(9) FIG. 11 illustrates anastomosis of aorta after Hemoblok application;

(10) FIG. 12 illustrates using the Hemoblok for hemostasis at wound sewn of the dog lung;

(11) FIG. 13 illustrates surgical suture after applying of Hemoblok composition;

(12) FIG. 14 shows diffuse bleeding during liver biopsy, and

(13) FIG. 15 shows the bleeding stopped by wound coated formed with Hemoblok composition.

DETAILED DESCRIPTION OF THE INVENTION

(14) Embodiments of the present invention are disclosed herein below with a view of disclosing both the present invention and equivalents thereof which are within reach of a skilled person having read the present application.

(15) In clinical practice, there are used different ways of influencing the source of the bleeding: diathermocoagulation, laser photocoagulation, cryotherapy, application of film-forming agents, irrigation and injection hemostatic solutions, and the introduction of vasoconstrictor and sclerosing agents. The subject of the present invention pertains to medical wound covering means and methods for stopping or decreasing the blood flow from an open wound or a medical or surgical procedure site.

(16) According to the first embodiment of the present invention, the medical wound covering means is prepared on the basis of composition having combined antibacterial and haemostatic properties, which has storage stability and long shelf-life.

(17) The haemostatic agent comprised in the used composition is a polyelectrolyte matrix which comprises at least one polymeric carboxylic acid of a predetermined average molecular weight range. The polymeric carboxylic acid is preferably a polymeric α,β-unsaturated carboxylic acid, particularly such as poly (acrylic acid), poly (methacrylic acid) or poly (crotonic acid), with poly (acrylic acid) being particularly preferred. The preparation may comprise a single such as acid, or a mixture of several α,β-unsaturated carboxylic acids.

(18) The concentration of the acid is preferably from about 0.5% to about 5% by weight, particularly from 0.5% to 2% by weight, with a concentration of 1% by weight being particularly preferred.

(19) The wound covering according to the present invention is prepared as the development of haemostatic bactericidal composition described in WO 01/41774 (A1). In compositions containing poly (acrylic acid) as the polymeric matrix, this polyacrylic acid has the structural formula [CH.sub.2—CHCO.sub.2H].sub.n, where n is its average molecular weight and is at least about 14, particularly from about 14 to about 1400, and preferably from about 14 to about 140. Poly (acrylic acid) having an average molecular weight of about 30 is particularly preferred.

(20) This composition has the bactericidal agent, which is an ionic silver releasing species and is selected from the group consisting of dissolved silver ions, oligomeric silver clusters, silver colloidal nanoparticles and any mixture thereof. The term “ionic silver releasing species” means any species that are capable of releasing silver ions into an aqueous solution containing the aforementioned composition.

(21) Particular ionic silver releasing species are dissolved, free silver ions, Ag.sup.+, which may be generated by soluble silver salts, such as silver nitrate or silver acetate, presenting in this water-soluble composition, oligomeric silver clusters, silver colloidal nanoparticles and any mixture thereof. The term “oligomeric silver cluster” as used herein is to be taken to mean substantially oligomeric silver cluster ions, also referred to as coordinate ions, such as Ag.sub.2.sup.1+, Ag.sub.4.sup.2+, Ag.sub.8.sup.2+ and the like. The term “silver nanoparticles” as used herein is to be taken to mean substantially metallic silver nanoparticles, preferably of a size from about 0.5 nm. to about 5 nm. Preferred embodiments of such composition contain from about 1×10.sup.−5 mole per liter to about 1 mole per liter silver.

(22) The pH of the haemostatic composition used according to this invention is preferably a pH between about 3 and about 10, for example, between about 6 and about 10, and particularly a pH that substantially equal to human blood physiological pH, i. e. about 7.3-7.6.

(23) The haemostatic compositions used herein may be in liquid form, particularly aqueous solutions having long shelf-life. The haemostatic compositions used herein may also be in dry, preferably freeze-dried form, for use by dissolution in pure water before use, to give a liquid preparation. The term “pure water” as used herein means distilled, deionized or otherwise purified water, which may be sterilized, and is physiologically compatible. The freeze-dried compositions may be stored over prolonged periods of time.

(24) The liquid as well as dried compositions may be incorporated in bandages or the like, or applied directly to a wound or to body tissue. The possibility of directly applying the compositions as used herein to wounds and body tissues, for example, during operation, is one of their major advantages.

(25) As described above, the compositions as used herein preferably comprise poly (acrylic acid) as the haemostatic agent, and silver ion releasing material as the bactericidal agent. Thus, the silver may be in a variety of forms including ions, oligomeric clusters and nanoparticles. The poly (acrylic acid) binds with the silver, has a stabilizing effect on the silver and prevents its precipitation. In some embodiments, the poly (acrylic acid) will trap the silver at the blood clot, slowly releasing silver ions, to provide long term, controlled antibacterial effect. This stabilizing effect confers long shelf life to the haemostatic, antibacterial compositions of the invention, which is another major advantage.

(26) According to the second embodiment of the present invention, the polyacrylic matrix structure comprises silver polyacrylate in very small amounts, comparable to natural blood coagulation factors. In this case, the polyacrylic matrix structure serves as the main organizer (plasticizer) of stable blood clot on the wound surface. That is silver polyacrylate acts as an artificial non-specific blood clotting factor-plasticizer.

(27) According to the third embodiment of the present invention, the medical wound covering means used herein may also be in spray form and can be prepared on the basis of haemostatic composition having combined antibacterial and haemostatic properties, which have storage stability and long shelf-life. The deposition of the composition is preferably achieved by application of its fluid or liquid form onto the surface of the wound, for example, by ultrasonic spray technology.

(28) It follows that a fluid or liquid form of haemostatic composition may be any liquid or gaseous composition, and covers any solution, suspension and emulsion. In this embodiment, the fluid or liquid composition is a particulate composition, which may be liquid, gaseous or dry. This composition may be employed if the size of the particles does not exceed the diameter of the ultrasonic spray nozzle from which the composition exits.

(29) Ultrasonic spray technology comprises use of ultrasonic nozzle systems for application of thin film coatings onto the wound according to the present invention. Advantages of using ultrasonic nozzle systems for coating of the wound include dramatic reduction in overspray, savings in raw materials, water and energy usage, improved process and transfer efficiency, greater uniformity and reduced emissions. Ultrasonic spray systems use high frequency sound vibrations and the nozzles atomize liquids to form a soft spray of micron-sized droplets.

(30) In this proposal, the most preferred source of spray appears pressureless, ultrasonic atomizing nozzles with a soft, low-velocity spray, typically on the order of 75-125 mm per second. These spray delivery means significantly reduces the amount of overspray since the drops tend to settle on the substrate, rather than bouncing off it. This translates into substantial material savings and reduction in emissions into the environment. The spray can be controlled and shaped precisely by entraining the slow-moving spray in an ancillary air stream.

(31) Since the ultrasonic atomization process does not rely on pressure, the amount of liquid atomized by a nozzle per unit time is primarily controlled by the liquid delivery system used in conjunction with a nozzle. The flow rate range for the used ultrasonic nozzles is as low as from a few microliters per second.

(32) Depending on the specific nozzle and the type of liquid delivery system employed, the technology is capable of providing an extraordinary variety of flow and spray possibilities. The liquid delivery system employed can be selected from the group consisting of one or more gear pumps, one or more syringe pumps, one or more pressurized reservoirs, one or more peristaltic pumps, and one or more gravity feeds.

(33) In general, the drops produced by ultrasonic nozzles have a relatively narrow size distribution. In one embodiment the median drop sizes range from 18-68 microns (μm), depending on the operating frequency of the specific type of the nozzle. As an example, for a nozzle with a median drop size diameter of approximately 40 microns, 99.9% of the drops will fall up to the 5-200 micron diameter range. Every ultrasonic nozzle operates at a specific resonant frequency, which is determined primarily by the length of the nozzle. Every ultrasonic nozzle operates at a specific resonant frequency, which is determined primarily by the length of the nozzle. The nozzle has a cone-shaped atomizing surface. Its purpose is to spread out the spray. Some applications require the spray to be very narrow. In those cases, the atomizing surface is sculptured into a flat or nearly-flat surface. Depending on the width requirements of the spray pattern and the required flow rate, the atomizing surface may have a very small diameter or an extended flat section. Drop size in an ultrasonically produced spray can be governed by the frequency at which the nozzle vibrates, and/or by the surface tension and/or density of the liquid being atomized. However, frequency is often the predominant factor. Thus, the higher the frequency, the smaller the median drop size is.

(34) How it Works

(35) The main idea of this invention is use of water solution to activate ionization, acid-base reactions, and related adhesion of compositions to mammalian tissue for hemostasis and/or tissue protection. It is known that viscosities of aqueous polyacrylic acid dispersions are increased by alkaline neutralization. This idea was initially applied to development of topical skin protectants, then to protective sealing of denuded wounds. The original idea was extended with the thought that artificial clotting of blood might result from ionization of the haemostatic components by the water in blood or serum. It was found that water solution, in blood or other leaking body fluids, activates ionization, acid-base reactions and related adhesion of compositions to mammalian tissue for hemostasis and/or tissue protection.

(36) Each application of the methods of this invention makes use of at least one polymeric carboxylic acid in a formulation optimized for the application. However, the polyacrylic acids known as carbomers or carboxypolymethylenes are preferable components. Furthermore, different carbomers are preferred for different applications and usage, as outlined above. Additionally, although non-polymeric components are critical for some applications or usages, ratios of polymeric and non-polymeric components are specific application. The polyacrylic acids may be of various chain lengths and modified monomer components, and have different cross-links as long as they have the monomeric chemical structure [CH.sub.2—CHCO.sub.2H].sub.n, where n is at least about 14, preferably is about 30. The polyacrylic matrix contains the polyacrylic acid, which has the structural formula [CH.sub.2—CHCO.sub.2H].sub.n, where n is from about 14 to about 1400, preferably from about 14 to about 140.

(37) Polyacrylic acid (also known as carboxypolymethylene) may be presented as a homopolymer in a family of acrylic acid derivatives known as carbomers. Their polyacrylic acid strands may be cross-linked to various degrees with groups such as allyl sucrose. Such carbomers actively absorb water, melt (without dissolving) at body temperatures, then swell. With water, they constitute a stiff mucilage that is biologically inert but adherent to wet tissue, thereby forming a clot-like wound sealant effective on mammalian tissue (human or non-human) with hemorrhage from trauma or defective blood clotting (from hemophilia or use of anticoagulant medications such as Coumadin).

(38) When the composition includes polyacrylic acid admixed with desiccated water-soluble organic or inorganic base, the acid moiety is neutralized to greater or lesser degree when the composition acquires enough water to support ionic interactions that form salts. Such neutralization, from about pH 4 to pH 8, is known to increase mucilage viscosity in aqueous dispersions.

(39) Medical means “Hemoblok” as used in the present invention, is a local hemostatic. It includes part-time silver salt of polyacrylic acid containing silver nanoparticles. This causes a pronounced bactericidal and bacteriostatic effect of Hemoblok. The hemostatic effect is achieved within 1-2 minutes due to formation by Hemoblok of clot with plasma proteins (mainly albumin).

(40) Recent studies have shown that the action mechanism of Hemoblok does not depend from concentration protein shelter clotting factors in the blood plasma, but depends mainly on the albumin content. Apply Hemoblok composition externally for parenchymal and capillary blood flow. This moistened sterile cotton or gauze pads are applied for the stoppage of bleeding and drying of the wound surface. For large wound surfaces Hemoblok is used as a spray.

(41) In the first stage of the Hemoblok composition use there is developed polyacrylic matrix structure containing albumin molecules in the cells of the polyacrylic matrix. This structure is the primary and during its existence is small, since polyacrylate-anion does not establish a strong connection with the proteins' functional groups and is held only by weak interactions. However, this structure is the primary organizer of the stable film.

(42) The rod-like particles 3 of polyacrylic matrix 1 wherein become centers of proteins' functional groups 5 binding which are adsorbed on the surface of the charged rod-like particles 3 (see. FIGS. 1 and 2). Simultaneously there can occur sorption of proteins' functional groups 5 by side surfaces of charged rod-like particles 3 of polyacrylate anion (FIG. 2). It can be assumed that the structure of such conglomerates of particles are formed by the circuit shown in FIG. 3 and leads ultimately to a hexagonal packing of polyacrylic matrix 1.

(43) The viscosity of the solution of thus forming complexes quite sharply increases with degree of polyacrylate anions polymerization. At the same time, sedimentation coefficient remains virtually unchanged. Such a relationship between these hydrodynamic parameters is possible only in the number of particles sufficiently elongated during their elongation. Assuming that the average length of the polyacrylate portion anion to be bounded by protein, is about 8×10.sup.−8 m and significantly is greater than the diameter of the forming complex. It can be assumed that these complexes are somehow joined together, forming a loop connected by straight portions (FIG. 4).

(44) Excess ionized groups, such as adjacent to the surface of the rod-like particles 3 of polyacrylic matrix 1 and located in loops 7 (FIG. 4) creating a hydrophilic zone extended along the surface of rod-like particles 3 promotes the retention of the protein particles in solution. The existence of the loops in the complexes is not dependent on the system viscosity as its water dilution, but is due to viscous electric effect associated with a “swelling” of free areas. In this unfinished revolution loop may be completed by another polyacrylate-anion and asymmetrical chain of protein globules in suitable conditions can be stabilized by relatively short polyacrylate anions rods, the length of which even are smaller than the diameter of the resulting complexes.

(45) The above proposed structure of the complex scheme is confirmed by electron microscopy (see. FIG. 5), which is a micrograph of the complex. In the picture there are clearly visible elongated linear formations consisting of linked to each other particles. The thickness of each of the linear formation is about 1×10.sup.−8 meters. Such complexes apparently are formed from polyacrylic acids and proteins by self-organization.

(46) The principle laid down by nature as the basis of Hemoblok building on the surface of the wound polyacrylic matrix structure containing albumin molecules in the cells of the polyacrylic matrix (grid) and is the primary organizer of sustainable polyacrylic film, apparently, is very general and its implementation needs to comply with two hydrodynamic conditions: 1) adhesion protein globules possible to open chain linear polyacrylate-anions, and 2) a sufficiently strong interaction of the adsorbed protein globules (functional groups) and complexes in general. Further feeding Hemoblok onto open wound surface leads to the formation thereon of the multilayer solid polymethacrylic film.

(47) As shown in FIGS. 6-9, the composition can be used in different embodiments of application.

(48) In the first embodiment of the invention, a composition as described above can be applied to a woven or non-woven fabric material 9, which is selected from the group consisting of gauze, paper, plastics, silicone polymers, resorbable materials, latexes and suitable derivatives of thereof (see. FIG. 6). At the same time this resorbable material is selected from the group consisting of proteinaceous materials, carbohydrate substances and resorbable suture materials.

(49) Woven or non-woven material 9 impregnated coated with the above composition is applied to the open surface of the wound and serves to protect it from further damage. Such damage may occur from a loss of substances by the body (such as water, blood, plasma, serum, proteins, electrolytes, nutrients), as well as for protection of the wound surface from access and further damage by conventional environmental substances (such as oxygen, dirt, foreign antigens proteins, pathogens, etc.). Wound covering with haemostatic composition in this embodiment secures the open surface of the wound and, accordingly, it is associated with ions physiologically balanced electrolytes to provide a physiological osmotic interaction and pH properties.

(50) In the second embodiment (not shown in the drawings), the polyacrylic matrix structure comprises silver polyacrylate in very small amounts, comparable to natural blood coagulation factors. In this case the polyacrylic matrix structure serves as the main organizer (plasticizer) of stable blood clot on the wound surface. That is silver polyacrylate acts as an artificial non-specific blood clotting factor-plasticizer.

(51) In the third embodiment, as shown in FIG. 7, the composition may be delivered to the open surface of the wound by using syringe type device 10. This hemostatic composition 12 may be pre-loaded into cylinder 14 of syringe 10 and extruded therefrom by pressing on handle 18 of stock 20. When there are any options of haemostatic composition, which needs not be premixed before application to the open wound, the delivery can be achieved by several parallel arranged cylinders 14 of syringe 10 (not shown).

(52) A preferred embodiment of apparatus 10 is shown in FIG. 7. Device 10 includes cylinder 14, which internal cavity 22 may be divided into separate sealed compartments for storage of composition 12, labeled as first storage compartment 24 and second storage compartment 26. Compartments 24 and 26 are sealed relative to one another during storage so that composition 12 in storage compartment 24 will not contact or otherwise interact with the composition in another storage compartment 26.

(53) Seals (not shown) are located within storage compartments 24 and 26 for composition 12 and serves to create a dynamic seal with the inner walls of compartments 24 and 26, so that when components of composition 12 are stored in compartments 24 and 26, there is no leakage through these seals. Thus, when piston 16 moves in a sliding motion within cylinder 14 toward distal end 28 of this cylinder 14, any components of composition 12 in compartments 24 and 26 are forcedly transported within said cylinder 14 towards its distal end 28. Usually cylinder 10 is equipped with a cap (not shown) for storage, and tip 30 is installed immediately before use of syringe 10.

(54) In the third embodiment, as shown in FIGS. 8 and 9, the composition may be delivered to the open surface of the wound using device 40. Device 40 may be in the form of mechanical or pneumatic gun 42 with composition 44 pre-loaded into chamber 46 of this gun 42. Upon manual actuation of control button 48 of gun 42 handle 50, composition 44 is forcibly ejected from distal end 52 of gun 42. Gun 42 can be equipped with a removable dilator (not shown in the drawings) at its distal end 52, which facilitates application of composition 44 in deep and/or on wide wounds.

EXAMPLES

(55) To determine the safety and effectiveness in achieving hemostasis in actively bleeding tissues influenced Hemoblok hemostatic composition for abdominal laparoscopic surgery, the laboratory and clinical studies have been conducted.

(56) On the first stage there were held the laboratory studies on animals (dogs). We determined the safety and efficiency of the hemostatic composition Hemoblok for abdominal surgery and the rate of achieving hemostasis in actively bleeding tissue of the abdominal cavity.

Example 1

(57) In the illustrated example of this laboratory study there was carried out at the treatment of aortic anastomosis at mongrel dogs. Hemostasis was occurred within 1.5 minutes (see FIGS. 10, 11). On FIG. 10 is visible anastomosis 60 of aorta 62 prior to the application Hemoblok. On FIG. 11 is seen anastomosis 64 of aorta 62 after application of Hemoblok, wherein the coating is formed as the clot elastic 66. Hemoblok Hemostatic composition in this case was delivered to the wound tissue by gauze napkin 68 impregnated with this composition.

Example 2

(58) In this case, it was carried out using the Hemoblok for hemostasis at wound sewn of the dog lung (wound depth of 1 cm, 3 cm length) (see FIG. 12). The lung thus performs its physiological function. In FIG. 12 is seen surgical suture 70 wound on the lung. Bleeding was stopped 60 seconds after Hemoblok contact with the wound surface of the dog. In FIG. 13 is visible surgical suture 70 after applying of Hemoblok composition. Delivery of the composition to the surface of the wound was carried out using a device such as a syringe 10.

Example 3

(59) The clinical studies were further conducted at human volunteers. The studies were conducted in Russia on the basis of the Department of Surgery at Municipal Clinical in the city of Kazan. The study including 26 patients were performed at the department of surgery. The purpose of research is clinical evaluation of safety and effectiveness in achieving hemostasis in actively bleeding tissue of the abdominal cavity under the influence Hemoblok composition for abdominal and laparoscopic surgery.

(60) The composition was used to diffuse (capillary) bleeding from the liver and dissected plane vistsero-visceral and vistsero-parietal adhesions in patients during surgical interventions for acute surgical pathology.

(61) The hemostatic effect was evaluated immediately after application (next 5 min) Hemoblok composition and 24 hours after the surgery. The etiology of diseases, which required surgery: acute destructive calculous cholecystitis—11 (42.3%), acute adhesive intestinal obstruction—15 (57.7%) cases. Depending on the method of delivery of a haemostatic Hemoblok composition on the bleeding surface to form a wound covering all the observed patients were divided into two groups.

(62) The first group included 11 patients who underwent endovideolaparoskopic cholecystectomy for acute calculous cholecystitis. Hemoblok was applied to the bleeding surface of the bed remote gallbladder through richly moistened (25 ml of the product) small gauze napkin. The last delivered to the wound surface through 5-mm. laparoscopic port.

(63) The second group included 15 patients with acute surgical pathology of abdominal organs, operated through the open method of laparotomy. Hemoblok was applied to an open wound surface by copiously moistened gauze napkin. Surgical treatment for acute destructive cholecystitis in all cases were performed by endovideolaparoskopic cholecystectomy. During the surgery all patients in this group occurred diffuse (capillary) bleeding from the gallbladder bed remote. During the operation, there was used coagulation, thus, artificially created by coagulation necrosis area increased postoperative risk of infectious complications. That is why another attractive aspect of the Hemoblok application was its antibacterial effect.

(64) Surgical treatment for acute adhesive intestinal obstruction in all cases were carried out by open laparotomy, viscerolise. During operations in all patients in this group occurred diffuse (capillary) bleeding from a plurality of planar adhesions dissected. Excessive coagulation of serous cover, unfortunately, did not provide adequate haemostatic effect, as well as in the first group of patients.

(65) In open surgery gauze napkin was moistened with an average of 25-50 ml Hemoblok composition, while the most difficult laparotomy a big gauze napkin was moistened by 100 ml. of composition. Before using these napkins on the bleeding surface a short pre-imposed a dry cloth were used. After its removal immediately was imposed napkin moistened with the Hemoblok composition. The exposition was 2-3 min. In all cases, stable hemostasis (see. FIGS. 14, 15) has been reached. In FIG. 14 shows diffuse bleeding during liver biopsy. In FIG. 15 shows how the bleeding was stopped by wound coated formed by Hemoblok composition.

(66) In 23 (88.5%) cases out of 26 was obtained stable hemostatic effect. The mean time of hemostasis was 2.09±0.2 and 2.53±0.15 minutes in the first and second groups of patients, respectively. In the first group of patients hemostasis was stopped for 1-3 minutes at 10 (90.9%) of 11 patients. This secondary bleeding and suppuration have not been fixed. At 1 (9.1%) patient in the first group there was a recurrence of the bleeding gallbladder bed remote, requiring repeat surgery (see. Table 1).

(67) TABLE-US-00001 TABLE 1 Hemostatic effect of Hemoblok during endovideolaparoskopic cholecystectomy Blood loss up The amount Final stop complete Bleeding Pronounced of Hemoblok, time of hemostasis, ## surface, cm.sup.2 bleeding ml bleeding, min ml 1 8.75 + 25 2.5 110 2 8.5 + 25 3 80 3 8.25 + 25 1 65 4 8 + 25 2 75 5 7.5 + 25 2 90 6 6.5 + 25 1.5 85 7 6.25 + 25 2.5 95 8 7.5 + 25 2 75 9 7.6 + 25 3 110 10 8.5 + 25 2 100 11 9.5 + 25 1.5 70 Total 7.86 ± 1.1 + 25 2.09 ± 0.2 86.81 ± 11.5

(68) In the second group of patients, 13 (86.7%) at the 15 patients there came hemostasis for 1-3 minutes. Secondary bleeding was not recorded. At 2 (13.3%) patients of the second group re-bleeding arose, requiring additional re-use of the Hemoblok composition with an exhibition of 4 minutes, so the total time of hemostasis in these patients was 6 minutes (Table. 2).

(69) TABLE-US-00002 TABLE 2 Hemostatic effect of Hemoblok during open laparotomy Blood loss up The amount Final stop complete Bleeding Pronounced of Hemoblok, time of hemostasis, ## surface, cm.sup.2 bleeding ml bleeding, min ml 1 18.5 + 100 2 250 2 18.5 + 100 1.5 280 3 18.5 + 100 2 180 4 10 + 100 2 175 5 15.5 + 100 2 290 6 16.5 + 100 2.5 185 7 18.5 + 100 1.5 190 8 25.5 + 100 1 300 9 17.5 + 100 2 250 10 22.5 + 100 6 300 11 19.5 + 100 2.5 270 12 20 + 100 3 280 13 21 + 100 2 250 14 22 + 100 6 290 15 15.5 + 100 2 270 Total 18.43 ± 2.3 + 100 2.53 ± 0.15 250.7 ± 7.5

(70) Thus, recurrent bleeding in both groups were observed at 3 patients (11.5%) patients. In all 3 cases, there were systemic violations of blood coagulation. No clinically significant adverse reactions associated with the use Hemoblok composition were observed. Conducted clinical analysis of the results of applying the composition to form Hemoblok protective wound coverings in surgical practice was attributed to its clinical advantages of the following aspects:

(71) Wound coverage with Hemoblok is an effective means for stopping diffuse (capillary) bleeding at various kinds of surgeries.

(72) Wound coverage using Hemoblok has antibacterial effects on the wound surface. Wound healing takes place without the use of antibiotics and other antibacterial agents.

(73) Called rapid hemostasis takes from 2.09±0.2 and up to 2.53±0.15 m. This blood loss was 86.81±11.5 and 250.7±7.5 ml at endovideolaparoskopic and open transactions respectively.

(74) In the process of applying of the Hemoblok composition was not observed postoperative complications as fistula, adhesion formation and the emergence of reactive effusions in the peritoneal cavity.

(75) In the near and distant postoperative, there were no any toxic and allergic reactions, irritation to the surrounding tissue and influence hemostasis in the general circulation.

(76) Wound coverage with Hemoblok compositions is easy to use, equally closes all irregularities on bleeding wound surfaces.

CONCLUSIONS

(77) 1. Wound coverage with Hemoblok is a sufficiently effective local hemostatic.

(78) 2. The hemostatic effect does not depend on the method of the Hemoblok composition delivery to a bleeding wound surface and manifests itself in open laparotomy, using endovideolaparoskopic technologies, etc.

(79) 3. During endovideolaparoskopic interventions efficient haemostatic effect of wound coverings using Hemoblok is evident in 90.9% of cases, and with open laparotomy—in 86.7%.

(80) 4. Infectious complications associated with the use of Hemoblok composition were not observed.

(81) 5. The Hemoblok can be used as an adjuvant treatment facility to deal with parenchymal bleeding during abdominal and laparoscopic surgery. Hemoblok Hemostatic composition is sufficiently effective local hemostatic.

(82) The wound covering on the base of Hemoblok hemostatic composition can also be provided as a spray or aerosol that can be directly applied to a wound. The applicators such as woven or non-woven fabric 9, syringe 10, or gun 42 and other suitable applicators can also be provided to allow rescue personal, emergency medical personnel, family members, or others with little or no professional medical training to apply the composition to wounds in emergency situations. The blood clotting composition is particularly useful for medical emergency first responders, police, and military personnel to stop bleeding from wounds in the field.

(83) The hemostatic composition, which typically will be applied to a wound by a first responder at the incident site can include as prophylactic antibiotic selected from antibiotic classes including: penicillin's, penicillin combinations, sulfonamides, as well as other suitable antibiotic compositions and combinations thereof.

(84) The wound covering on the base of Hemoblok compositions and proposed method of the subject invention may be widely useful, for instance, in the following applications:

(85) Preventing hemorrhage or minor bleeding at the site of injury by artificially coagulating blood, adhering the blood or product coagulum, immobilizing damaged tissue to minimize further injury, and preventing further contamination of a wound;

(86) Protecting of wounds from possible injury by coating them with semi-permeable barrier films;

(87) Surgical use to accelerate epithelialization of denuded surfaces, preventing excessive formations of connective tissue during wound healing, temporary sealing of the bleeding edges of soft internal organs such as liver, spleen, or lung prior to the application of biodegradable materials by highly skilled surgeons;

(88) Use as a bioadhesive to stabilize damaged tissue as a soft tissue splint, coat and seal raw surfaces such as blister bases, abrasions or burns;

(89) Use as a means for delivery of drugs to or through wounded surfaces.

(90) It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application. In addition, any elements or limitations of any invention or embodiment thereof disclosed herein can be combined with any and/or all other elements or limitations (individually or in any combination) or any other invention or embodiment thereof disclosed herein, and all such combinations are contemplated with the scope of the invention without limitation thereto.