Pharmaceutical composition for providing temporary haemostasis in the case of non-major bleeds

Abstract

The group of inventions relates to the field of medicine, and more particularly to haemostatics and drugs for providing temporary haemostasis in the case of non-major bleeds. Proposed are a pharmaceutical composition containing tranexamic acid, chlorhexidine digluconate, bupivacaine, and water, in the following proportions: 13-16 wt.% tranexamic acid, 2.00 wt.% chlorhexidine digluconate, 0.5 wt.% bupivacaine, and 81.5-84.5 wt.% water, and a drug in aerosol or spray form comprising said pharmaceutical composition. Use of the group of inventions makes it possible to stop bleeds very quickly and reduce the risk of renewed bleeding. In addition, providing the drug in the form of an aerosol or spray allows easy and convenient use. The proposed composition and drug can be used for providing temporary haemostasis in the case of non-major bleeds in the fields of dentistry, veterinary medicine, military field medicine, disaster medicine, and the like.

Description

[0001] A PHARMACEUTICAL COMPOSITION FOR PERFORMING TEMPORARY HEMOSTASIS IN NON-MAGISTRAL BLEEDING AND A MEDICINAL PRODUCT CONTAINING THIS PHARMACEUTICAL COMPOSITION

[0002] MIC: A61K 31 / 155, A61K 31 / 195 (2006.01), A61K 31 / 445 (2006.01), A61K 9 / 08 (2006.01), A61K 9 / 12 (2006.01), A61R 7 / 04 (2006.01), A61R 17 / 02 (2006.01)

[0003] The claimed group of inventions relates to the field of medicine, in particular to medicinal products for the treatment of disorders of the blood or extracellular fluid, namely to hemostatic agents and medicinal products for performing temporary hemostasis in non-major bleeding.

[0004] Non-major hemorrhages, which do not involve damage to major blood vessels, are a common injury in various areas of life and often do not require mandatory hospitalization or surgical intervention to stop the bleeding. Known medications used to stop bleeding are often administered parenterally, particularly by injection. However, ensuring the necessary conditions for such administration in domestic or military field conditions is challenging due to the need to comply with safety requirements, the availability of injection equipment (syringes or intravenous catheters), and the need for specialized skills to perform the necessary procedures. Furthermore, like any other injury, non-major hemorrhages are accompanied by pain and the risk of infection, and in the absence of prolonged medical care, the risk of blood loss.Thus, the creation of a pharmaceutical composition for temporary hemostasis in non-mainstream bleeding (for example, to provide first aid and ensure the ability to transport the victim to a medical facility), as well as a medicinal product containing such a composition in a dosage form convenient for use by people who are not medical specialists, is a pressing task.

[0005] The prior art discloses hemostatic agents based on various compounds and in various forms. For example, a composite biomaterial is known that has hemostatic and regenerative activity, cross-linked from collagen polypeptides with an average molecular weight of at least 100,000 daltons and a fraction of active peptides with a molecular weight of 3,600 to 10,000 daltons, formed by enzymatic cleavage of collagen polypeptides, in the following ratio, wt. %: collagen polypeptides: 90-95, fraction of active peptides: 1-4, excipients: the rest. Russian Federation Patent No. RU 2794766C, IPC A61K 38 / 39, A61K 38 / 01, A61K 31 / 315, A61P 7 / 04, A61P 17 / 02, published. April 24, 2023.

[0006] A local hemostatic agent is also known for stopping bleeding of varying severity, which is granules of 0.5-2.0 mm in size made of a porous material, wherein the granule material is obtained by hydrothermal synthesis and is characterized by a composition, mass %: synthetic zeolite of the type CaX(0.40-0.48)CaO-(0.08-0.16)Na2O-(2.50-3.00)SiO2-Al2O3-(1.0-1.50)H2O 75-85, metakaolin 2.0SiO2-Al2O310-20, calcium chloride is the rest. Russian Federation Patent No. RU 2805923C1, IPC A61K 33 / 06, A61K 33 / 08, A61K 33 / 14, A61P 7 / 04, published. 24.10.2023.

[0007] A hemostatic composition with reparative properties in the form of a sponge is known, containing xymedon, a biopolymer, glycerin and water. The composition contains modified chitosan as a biopolymer, in the following ratios of components, mass. %: xymedon 42, SO-45, 00, modified chitosan 40.10-48.20, glycerin 6.40-11.75, water (the rest). It may additionally contain an antiseptic. Russian Federation Patent No. RU 2720627C1, IPC A61K 31 / 722, A61K 31 / 505, A61P 7 / 04, published.

[0008] 12.05.2020.

[0009] The closest prior art analogue chosen was a solution comprising a hemostatic anti-burn wound-healing composition containing an active gelling component, an active plasticizer, and active and auxiliary ingredients. The active gelling component is a water-soluble heteropolymer of chitosonium salt with the general formula: [(C8H 13 NO5) 1.m (C6H 12 N + O4X') m ]n, where (C8H13 NO5) is the gross formula of the elementary unit of chitin; (C6HI2N +O4X') is the gross formula of the elementary unit of the chitosonium salt; X' is chloride, formate, acetate, oxalate, succinate, citrate, glycolate, or lactate anions, sh is the degree of chitin deacetylation from 0.7 to 1.0, n is the number of elementary units in the heteropolymer from 10 to 1000, in an amount from 1.0 to 10.0 (wt.%). As an active plasticizer, the composition contains the medicinal substance of dexpanthenol and / or 2-allyloxyethanol in an amount from 1.0 to 10.0 (wt.%). The composition contains immobilized medicinal substances of aminocaproic or tranexamic acid as active ingredients in an amount of 0.1 to 5.0 (wt.%) and calcium chloride in an amount of 0.05 to 2.0 (wt.%). As auxiliary ingredients, the composition contains immobilized medicinal substances of lidocaine or anilocaine in an amount of 0.1 to 5.0 (wt.%) and chlorhexidine in an amount of 0.005 to 0.1 (wt.%). The remainder is water.RF patent No. RU 2526183С1, MPK A61K 47 / 36, A61K 9 / 06, A61K 31 / 722, A61F 13 / 02, publ.

[0010] 20.08.2014. The distinctive feature of the claimed pharmaceutical composition for temporary hemostasis in non-major bleeding is the provision of effective anti-inflammatory action due to the combination of the claimed components, as well as a convenient dosage form of the drug, including the pharmaceutical composition, for use, including in domestic and military field conditions.

[0011] The objective of the claimed technical solution is to create a pharmaceutical composition, as well as a medicinal product including such a pharmaceutical composition, for performing temporary hemostasis in non-major bleeding, ensuring a fast and effective hemostatic effect and the possibility of easy and convenient use.

[0012] The technical result of the claimed solution consists in the creation of a pharmaceutical composition for performing temporary hemostasis in non-major bleeding, as well as a medicinal product containing such a composition, with high efficiency.

[0013] An additional technical result of the claimed solution is to ensure the antiseptic action of the pharmaceutical composition, as well as to increase the ease of use of the medicinal product containing such a composition.

[0014] The effectiveness of the claimed pharmaceutical composition is achieved, in particular, by a high rate of bleeding arrest and a reduced risk of recurrence. Increased ease of use of the medicinal product, including the pharmaceutical composition for temporary hemostasis of non-major bleeding, is achieved, in particular, by its ease of use. The claimed technical results are achieved due to the fact that the pharmaceutical composition for temporary hemostasis of non-major bleeding includes tranexamic acid, chlorhexidine bigluconate, and water in the following component contents, in mass %: tranexamic acid 11-19, chlorhexidine bigluconate 0.05-2.00, water 80-88.

[0015] The claimed technical results are also achieved due to the fact that the medicinal product, which includes a pharmaceutical composition for performing temporary hemostasis in case of non-trench bleeding, including tranexamic acid, chlorhexidine bigluconate and water with the following content of components, mass %: tranexamic acid 11-19, chlorhexidine bigluconate 0.05-2.00, water 80-88, is made in the form of an aerosol or spray.

[0016] In the context of the claimed solution, a pharmaceutical composition for temporary hemostasis in non-major bleeding and a medicinal product containing this composition can be used for local and external use, for example, for application to the skin, mucous membranes of the mouth and nose, gums, etc.

[0017] The claimed pharmaceutical composition for temporary hemostasis in non-major bleeding, as well as a medicinal product made on its basis, can be used to stop bleeding, in particular in cuts, nosebleeds, postoperative bleeding in dentistry or otolaryngology, as well as in veterinary medicine, in which there is no damage to large main blood vessels that contribute to significant blood loss and require the most immediate medical care.

[0018] A pharmaceutical composition for temporary hemostasis of non-major bleeding includes tranexamic acid, which is known to be a synthetic derivative of the amino acid lysine and has an antifibrinolytic effect by reversibly blocking lysine binding sites on plasminogen molecules, inhibiting its interaction with lysine residues on the fibrin surface, and, as a result, binding to fibrin and its destruction, which prolongs the dissolution of formed fibrin clots, reducing blood loss, and also lowering the risk of rebleeding [1]. Tranexamic acid is widely known to be effective in a wide range of hemorrhagic conditions, in particular to reduce postoperative blood loss and the need for blood transfusion in cardiac surgery, maxillofacial surgery, gastrointestinal bleeding, in obstetrics and gynecology, etc.Furthermore, tranexamic acid is better tolerated by patients than, for example, another antifibrinolytic, ε-aminocaproic acid. It is also less prone to thromboembolic complications and can be used in combination with anticoagulants. It also reaches peak plasma concentrations more quickly [2, 3], ensuring its effectiveness. Tranexamic acid also exhibits some anti-inflammatory activity [4, 5], which may further enhance the effectiveness of the claimed composition for temporary hemostasis in non-major bleeding, reducing the risk of wound tissue inflammation, which impairs wound healing and increases the risk of rebleeding.In addition, tranexamic acid may promote skin repair to some extent by increasing occludin levels and restoring skin barrier properties [6], which may further accelerate skin healing and reduce the risk of recurrence of bleeding. Although the most common route of administration of tranexamic acid is oral (in the form of tablets) and parenteral (intravenous) administration, there is evidence for its topical use in various areas with sufficient effectiveness in reducing blood loss [7, 8].

[0019] The claimed pharmaceutical composition includes tranexamic acid at a concentration of 11-19% by weight, which ensures rapid bleeding control and reduces the risk of rebleeding, for example, in the event of re-injury to the wound, particularly in the case of suture failure or accidental injury. Tranexamic acid levels below 11% by weight contribute to slow bleeding control and increase the risk of rebleeding. Tranexamic acid levels in excess of 19% by weight in the claimed pharmaceutical composition may increase the risk of allergic reactions and side effects, thereby reducing the safety of the claimed solution.

[0020] A pharmaceutical composition for temporary hemostasis of non-major bleeding includes chlorhexidine bigluconate, which, due to its low toxicity, is widely used as an antiseptic and disinfectant in virtually all areas of medicine due to its high antibacterial activity [9]. The presence of this component in the composition provides the antiseptic effect of the composition, preventing infection and inflammation of tissues at the bleeding site, which can inhibit their healing, as well as stopping bleeding, reducing the rate and reducing the effectiveness of the composition.

[0021] The claimed pharmaceutical composition includes chlorhexidine bigluconate in a concentration of 0.05-2.00% by weight, which imparts an antiseptic effect and further reduces the risk of rebleeding. The presence of chlorhexidine bigluconate in a concentration of less than 0.05% by weight does not reduce the risk of wound tissue inflammation during healing and recurrence of bleeding, likely due to its possible washout from the application area during bleeding and a further decrease in its concentration. Furthermore, a chlorhexidine bigluconate concentration in the pharmaceutical composition exceeding 2.00% by weight may increase the risk of allergic reactions and side effects, thereby reducing the safety of the claimed solution.

[0022] The combination of tranexamic acid and chlorhexidine bigluconate in the claimed amounts in the composition of the claimed pharmaceutical composition makes it possible to reduce the individual content of these components due to the combination of the anti-inflammatory action of tranexamic acid and the antiseptic action of chlorhexidine bigluconate, thereby reducing the risk of allergic or local toxic reactions, increasing the safety of the composition, while maintaining high efficiency, preventing the proliferation of pathogenic microorganisms near or directly in the wound and reducing the risk of inflammation of the tissues of the wound surfaces caused by such microorganisms.

[0023] The water-based formulation of the pharmaceutical composition for temporary hemostasis of non-major bleeding, particularly the inclusion of water, increases the versatility of the claimed composition for bleeding in various locations, unlike alcohol-based solutions, including the oral cavity, skin, respiratory tract, hearing organs, etc., reducing the risk of toxicity and ensuring a highly effective and safe solution. Furthermore, the claimed components are highly soluble in water, whereas tranexamic acid is virtually insoluble in alcohol, which, when used as a solvent, reduces the effectiveness of tranexamic acid in stopping bleeding.Moreover, the pharmaceutical composition's formulation in liquid form (as an aqueous solution), as opposed to, for example, a powder or tablet dosage form, increases the rate of absorption of the composition's components, particularly tranexamic acid, and accelerates the composition's hemostatic action, especially with topical and external use. Furthermore, the formulation of the claimed composition as an aqueous solution ensures good wettability of the skin and mucous membranes, which improves wound coverage and accelerates the absorption and action of the composition's active ingredients, further enhancing its effectiveness.

[0024] The claimed pharmaceutical composition includes water in a content of 80-88% by weight, which reduces the risk of allergic and toxic reactions caused, in particular, by a decrease in the water content to less than 80% by weight and, consequently, an increase in the content of the composition's active components (tranexamic acid and chlorhexidine). It also ensures the composition's effectiveness, since increasing the water content above 88% by weight reduces the amount of active ingredients in the composition. Furthermore, in various specific embodiments, the claimed composition, due to its liquid aqueous form, can be used to impregnate dressings, cotton or gauze swabs, and also as an aerosol or spray.

[0025] The effectiveness of the claimed composition for temporary hemostasis in non-major bleeding may be due, in particular, to the fact that this type of bleeding is not accompanied by rapid and profuse blood loss that would wash the composition out of the wound and prevent the absorption and action of the components. In a preferred embodiment, the pharmaceutical composition for temporary hemostasis in non-major bleeding comprises the claimed components in the following content, wt. %: tranexamic acid 13-16, chlorhexidine bigluconate 2, water (the remainder), which, as has been experimentally shown, ensures rapid cessation of non-major bleeding, as well as the lowest risk of recurrence of bleeding.

[0026] In particular embodiments, for example for use in the field of disaster medicine or venereal field medicine, the claimed pharmaceutical composition may additionally include bupivacaine in a content of 0.1-1.0 wt. %, which, by blocking the sodium channels of the cytoplasmic membrane of neurons, suppresses the generation of action potentials and prevents the propagation of an impulse along nerve fibers, providing an additional long-term local anesthetic effect

[0010] of the claimed composition. The presence of this component in the composition reduces the pain syndrome from the resulting injury and bleeding, which also additionally prevents possible repeated damage to the wound due to irritation and self-trauma, especially when using the claimed composition in veterinary medicine, and the risk of resumption of bleeding, which also additionally increases the effectiveness of the claimed pharmaceutical composition. The presence of bupivacaine, in a particular embodiment, in a content of less than 0.1 wt.% does not provide an effective anesthetic effect due to possible washout of the composition from the wound and a further decrease in the bupivacaine concentration, which increases the risk of re-injury to the wound surface due to severe pain. Furthermore, increasing the bupivacaine content in the claimed pharmaceutical composition to more than 1% by weight may further increase the risk of allergic reactions, side effects, and local toxicity in the nervous system, further reducing the safety of the claimed solution.

[0027] The combination of the components in the claimed quantities in this particular embodiment of the pharmaceutical composition for temporary hemostasis in non-mainstream bleeding further accelerates the stopping of bleeding, in contrast to the use of an aqueous solution of tranexamic acid without chlorhexidine bigluconate and bupivacaine, which may be due to the prevention of the development of microorganisms in the wound, which can slow down healing and, as a consequence, increase the time it takes to stop bleeding, as well as the additional anesthetic effect of the composition, which further reduces pain from injury and reduces the risk of repeated injury to the wound, resuming bleeding, due to irritation and pain in conscious or unconscious attempts to relieve pain or irritation.

[0028] In a preferred embodiment, the pharmaceutical composition for temporary hemostasis in non-major bleeding comprises the claimed components in the following content, wt. %: tranexamic acid 13-16, chlorhexidine bigluconate 2, bupivacaine 0.5, water (the rest), which, as has been experimentally revealed, ensures rapid stopping of non-major bleeding, as well as the lowest risk of recurrence of bleeding.

[0029] In other particular embodiments, the pharmaceutical composition may additionally include various components, in particular those selected from the group consisting of vitamin B 12, vitamin C, sodium chloride, or a mixture thereof, in a content of 0.1-1.0 wt.%.

[0030] The claimed pharmaceutical composition can be used to produce a medicinal product in the form of an aerosol or spray for temporary hemostasis in case of non-major bleeding. Such a medicinal product in the form of an aerosol or spray, comprising a pharmaceutical composition for temporary hemostasis in case of non-major bleeding, comprising tranexamic acid, chlorhexidine bigluconate and water with the following content of components, in mass %: tranexamic acid 11-19, chlorhexidine bigluconate 0.05-2.00, water 80-88, - allows for the rapid stopping of non-major bleeding, providing the drug with high efficiency due to the qualitative and quantitative composition of the pharmaceutical composition used, providing the previously described effects, and also in connection with the production of the medicinal product in the form of an aerosol or spray, which significantly increases the ease of use of the drug, while also increasing its efficiency.

[0031] Providing a medicinal product as an aerosol means delivering the claimed pharmaceutical composition to the site of administration under excess pressure in the container, forming a dispersed aerosol system. Providing a medicinal product as a spray means delivering the claimed pharmaceutical composition to the site of administration from a container in which the claimed composition is under atmospheric pressure, using mechanical action to also form a dispersed aerosol system. In the context of the claimed solution, it should be understood that when using the term "the medicinal product is provided as an aerosol or spray," it refers to the dosage form of the drug, whereas the dispersed liquid / gas system formed during delivery of the pharmaceutical composition will be referred to as the "dispersed aerosol system" for the sake of distinction.

[0032] The formation of a dispersed aerosol system during the use of the claimed medicinal product, formulated as an aerosol or spray containing the claimed pharmaceutical composition, enables easy and uniform coverage of wound surfaces with the composition, exerting an antiseptic effect not only directly on the wound but also at the periphery, preventing the penetration of microorganisms from adjacent skin areas, thereby enhancing the effectiveness of the medicinal product. Furthermore, the ability to uniformly cover the wound surface with the composition through the formation of a dispersed aerosol system reduces the risk of localized bleeding and allows for the control and subsequent prevention of bleeding uniformly and quickly across the entire wound surface, further enhancing the effectiveness of the medicinal product.

[0033] Providing the drug as an aerosol or spray allows for both topical and external use, which can further reduce the risk of side effects from the systemic effects of the drug's components and, consequently, further enhance the safety of the claimed drug, which includes a pharmaceutical composition for temporary hemostasis of non-major bleeding. Furthermore, this formulation allows for use by individuals without specialized medical knowledge or resources for, for example, parenteral administration, simply by spraying the aerosol dispersed system onto the wound surface, significantly increasing ease of use and expanding the range of applications of the claimed drug.Moreover, the claimed composition in the form of a dispersed aerosol system after spraying does not require its removal from the wound surface after the effect has been achieved, and also does not require a long wait for further manipulation of the wound surface, for example, when used in dentistry, in contrast to, for example, hemostatic sponges, which require waiting for resorption, which also significantly increases the ease of use of the claimed medicinal product, including the claimed pharmaceutical composition.

[0034] The presence of microdroplets of the pharmaceutical composition in a dispersed aerosol system improves wound coverage and absorption by increasing the specific surface area, which also enhances the drug's effectiveness. Furthermore, the use of water as the primary solvent in the claimed pharmaceutical composition, which includes the claimed medicinal product, along with its formulation as an aerosol or spray, helps prevent potential side toxicity due to high concentrations, particularly of propellant and ethanol, which are necessary for the operation of the ejection system used in aerosols based on, for example, fluorocarbon propellants.In addition, unlike the use of the claimed pharmaceutical composition for impregnating dressings, cotton or gauze swabs, the production of the claimed medicinal product in the form of an aerosol or spray further reduces the risk of recurrence of bleeding, since after removal of the dressing or swab impregnated with the composition from the wound surface, it is possible to remove the formed blood clots that prevent bleeding, as a result of which recurrence of bleeding may be observed.

[0035] Thus, the production of the claimed medicinal product in the form of an aerosol or spray, including the claimed pharmaceutical composition, ensures effective hemostasis in non-major bleeding, along with high convenience and ease of use.

[0036] In a preferred embodiment, a medicinal product made in the form of an aerosol or spray, comprising a pharmaceutical composition for temporary hemostasis in non-major bleeding, with the following content of components in the composition, in mass %: tranexamic acid 13-16, chlorhexidine bigluconate 2, water (the rest), provides the preferred effectiveness of the medicinal product in accordance with the effects described earlier.

[0037] In a preferred embodiment, the medicinal product, made in the form of an aerosol or spray, includes a pharmaceutical composition, additionally including bupivacaine in a content of 0.1 - 1.0 wt. %, which, when the medicinal product is made in the form of an aerosol or spray, additionally provides a long-lasting local anesthetic effect in the wound and on peripheral surfaces, reducing pain, and also further simplifies the use of such a version of the drug in case of trauma in military field medicine, disaster medicine, or in case of trauma in animals, due to a reduction in the need for local anesthesia with the use of additional drugs in other dosage forms and special medical devices, in particular, for intramuscular administration.In addition, the use of this version of the drug further reduces the risk of recurrence of bleeding due to tissue damage due to irritation or pain, which further increases the effectiveness of the drug.

[0038] In a preferred embodiment, a medicinal product made in the form of an aerosol or spray, comprising a pharmaceutical composition for performing hemostasis in non-major bleeding, with the following content of components in the composition, in mass %: tranexamic acid 13-16, chlorhexidine bigluconate 2, bupivacaine 0.5, water (the rest), ensures the preferred effectiveness of the medicinal product in accordance with the effects described earlier.

[0039] In other particular embodiments, a medicinal product made in the form of an aerosol or spray may include a pharmaceutical composition additionally containing various components, in particular those selected from the group including vitamin B 12, vitamin C, sodium chloride, or a mixture thereof, in a content of 0.1-1.0 wt.%.

[0040] The achievement of the claimed technical result using a medicinal product containing the claimed pharmaceutical composition was demonstrated by performing temporary hemostasis for non-major bleeding in animals. For this purpose, an animal (pig) under general anesthesia was incised through the skin and fat layer, up to 4 cm deep. Bleeding from the wound surfaces was observed, caused by damage to non-major blood vessels.

[0041] After making the incision, a medicinal product in the form of a spray was used, containing the claimed pharmaceutical composition, including tranexamic acid, chlorhexidine bigluconate and water in accordance with the component contents presented in Table 1, by spraying the dispersed aerosol system of the pharmaceutical composition onto the wound bleeding surfaces, immediately after which the remaining blood from the initial bleeding was removed with a gauze swab.

[0042] Table 1

[0043]

[0044] Table 2 also presents examples of the compositions of a pharmaceutical composition including tranexamic acid, chlorhexidine bigluconate and water, as well as additionally bupivacaine in a content of 0.1-1.0 wt.%.

[0045] Table 2

[0046]

[0047] After application of the drug, after 15-20 seconds, for all samples No. 1-13, cessation of non-mainstream bleeding was observed, which indicates the high efficiency of the claimed pharmaceutical composition and the medicinal product made in the form of an aerosol or spray (i.e., allowing to obtain a dispersed aerosol system), including the claimed pharmaceutical composition.

[0048] The wound was then closed with sutures. One day after application of the pharmaceutical composition via a spray, there were no signs of hematoma in the wound area, indicating no recurrence of bleeding.

[0049] When the wound surfaces were separated and the wound was opened, minor bleeding from the capillaries was observed compared to the moment immediately after the incision was made, which indicates a reduced risk of recurrence of bleeding and the effectiveness of the claimed pharmaceutical composition and the medicinal product, made in the form of an aerosol or spray, including the claimed pharmaceutical composition.

[0050] Furthermore, the formulation of the claimed medicinal product as an aerosol or spray significantly increased its ease of use for temporary hemostasis of non-major bleeding due to its ease of application and the elimination of the need for specialized medical devices for administration, such as syringes or intravenous catheters. Fig.1 and 2 show images of wound surfaces at various stages of temporary hemostasis using a medicinal product in the form of a spray, including a pharmaceutical composition with a composition according to samples No. 1 and No. 8, respectively: top left - before treatment with the medicinal product; top right - 15 seconds after treatment with the medicinal product (with preliminary removal of blood from bleeding immediately after application for a more visual demonstration); bottom left - a suture 24 hours after treatment with the medicinal product; bottom right - after opening the wound 24 hours after treatment with the medicinal product. Images before and after use of other versions of the medicinal product in the form of a spray, including other samples of the pharmaceutical composition according to Tables 1 and 2, are not shown, since they had similar results both in terms of bleeding stop time, from 15 to 20 seconds, and in visual observation.

[0051] Specific formulations of a pharmaceutical composition containing tranexamic acid at a content of 13-16% by weight, chlorhexidine bigluconate at a content of 2% by weight, and water (the remainder), as well as, in some embodiments, additionally containing bupivacaine at a content of 0.5% by weight, provided the most favorable effect of the composition, demonstrating the shortest time to stop bleeding and the greatest reduction in the risk of rebleeding. Moreover, the presence of bupivacaine in the composition in the claimed amount did not impair the effect of tranexamic acid and chlorhexidine bigluconate in the claimed amounts, providing an additional anesthetic effect. For reasons of humanity, similar experimental work to prove this additional anesthetic effect of the composition in combination with the hemostatic and antiseptic effects was not conducted outside of general anesthesia; however, based on the aforementioned theoretical data and medical sources, it follows that such an effect is present in the composition.

[0052] The claimed group of inventions, namely a pharmaceutical composition, as well as a medicinal product made in the form of an aerosol or spray, including the claimed pharmaceutical composition, can be used to perform temporary hemostasis in non-mainstream bleeding in the field of dentistry, veterinary medicine, military field medicine, disaster medicine, etc., and are characterized by high efficiency, as well as high ease of use when using the claimed medicinal product.

[0053] The presented examples of composition, design, and use of the claimed pharmaceutical composition, as well as the medicinal product incorporating the claimed pharmaceutical composition, do not exhaust the possible embodiments and do not in any way limit the scope of the claimed technical solution. Other embodiments are possible within the scope of the claimed formula.

[0054] 1. Dunn S. J., Goa K. L. Tranexamic acid: a review of its use in surgery and other indications / / Drugs. - 1999. - V. 57. - No. 6. - P. 1005-1032.

[0055] 2. Vasiliev S. A., Vinogradov V. L., Gemdzhyan E. G. Tranexam - antifibrinolytic hemostatic / / Thrombosis, hemostasis and rheology. - 2008. - No. 1. - P. 28-34. 3. Tengborn L. Fibrinolytic inhibitors in the management of bleeding disorders / / Treatment of Hemophilia. - 2007. - V. 42. - P. 1-15.

[0056] 4. Jimenez JJ, Iribarren JL, Brouard M., Hernandez D., Palmero S., Jimenez A., Lorente L., Machado P., Borreguero JM, Raya JM, Martin B., Perez R., Martinez R, Mora ML Safety and effectiveness of two treatment regimens with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double -blind, dose-dependent, phase IV clinical trial / / Journal of cardiothoracic surgery. - 2011. - V. 6. - P.

[0057] 1-10.

[0058] 5. Jimenez J. J., Iribarren J. L., Lorente L., Rodriguez J. M., Hernandez D., Nassar I., Perez R., Brouard M., Milena A., Martinez R., Mora M. L. Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial / / Critical Care. - 2007. - V. 11. - P.

[0059] 1-10.

[0060] 6. Yuan C., Wang X. M., Yang L. J., Wu P. L. Tranexamic acid accelerates skin barrier recovery and upregulates occludin in damaged skin / / International Journal of Dermatology. - 2014. - V. 53. - №. 8. - P. 959-965.

[0061] 7. Montroy J., Hutton B., Moodley P., Fergusson N. A., Cheng W., Tinmouth A., Lavallee L. T., Fergusson D. A., Breau R. H. The efficacy and safety of topical tranexamic acid: a systematic review and meta-analysis / / Transfusion Medicine Reviews. - 2018. - V. 32. - №. 3. - P. 165-178.

[0062] 8. Hosseinialhashemi M., Jahangiri R., Faramarzi A., Asmarian N., Sajedianfard S., Kherad, Soltaniesmaeili A., Babaei A. Intranasal topical application of tranexamic acid in atraumatic anterior epistaxis: a double-blind randomized clinical trial / / Annals of Emergency Medicine. - 2022. - V. 80. -No. 3. - P. 182-188.

[0063] 9. Zverkov A. V., Zuzova A. P. Chlorhexidine: the past, present and future of one of the main antiseptics / / Clinical microbiology and antimicrobial chemotherapy. - 2013. - V. 15. - No. 4. - P.

[0064] 279-285.

[0065] 10. Karunarathna I., Tharayil AS Unveiling the Potency of Bupivacaine: A Comprehensive Review of Mechanism, Safety, and Clinical Applications / / Uva Clinical Lab. Retrieved from Unveiling the Potency of Bupivacaine: A Comprehensive Review of Mechanism, Safety, and Clinical Applications. - 2024.

Claims

A PHARMACEUTICAL COMPOSITION FOR PERFORMING TEMPORARY HEMOSTASIS IN NON-MAGISTRAL BLEEDING AND A MEDICINAL PRODUCT CONTAINING THIS PHARMACEUTICAL COMPOSITION 1. A pharmaceutical composition for temporary hemostasis in non-major bleeding, containing tranexamic acid, chlorhexidine bigluconate, bupivacaine and water in the following component content, mass %: tranexamic acid 13-16 chlorhexidine bigluconate 2.00 bupivacaine 0.5 water 81.5-84.5 2. A medicinal product for temporary hemostasis in non-mainstream bleeding, made in the form of an aerosol or spray, including a pharmaceutical composition containing tranexamic acid, chlorhexidine bigluconate, bupivacaine and water with the following component content, mass %: tranexamic acid 13-16 chlorhexidine bigluconate 2.00 bupivacaine 0.5 water 81.5-84.5

Images