Composition for treating and healing wounds

Abstract

The invention relates to medicinal compositions for treating and healing wounds and can be used, in particular, for treating and healing septic wounds, infected post-operative wounds, trophic ulcers, diabetic foot and the like in the contexts, inter alia, of disaster medicine and military medicine. A composition for treating and healing wounds at least contains highly dispersed silica, hydrophobic silica and a cationic surfactant, and further contains a mineral substance from the group of aluminosilicates, and additional components in the claimed proportions expressed in wt%. The technical result is that of: increasing the efficacy of the composition with respect to infected tissue; increasing the functionality of the composition; enabling the sorption of low-molecular-weight positively charged substances such as biogenic amines, heavy metal ions and hydrophilic and hydrophobic products of tissue degradation; lending the composition an efficient haemostatic effect; accelerating the rejection and breakdown of necrotic tissue while avoiding gradual debridement that entails repeated surgical interventions and reducing the number of medical procedures, including the application of dressings; and increasing the packing density and reducing the dustiness of the composition.

Description

[0001] Composition for treatment and healing of wounds

[0002] The invention relates to medicinal compositions for the treatment and healing of wounds and can be used for the treatment of, in particular, purulent wounds, postoperative infected wounds, trophic ulcers, diabetic foot, and the like, including within the framework of disaster medicine and in military medicine.

[0003] A wound healing agent is known from the prior art (patent for invention UA ​​21687 A, IPC A61K38 / 48, A61P17 / 02, C01B33 / 12, published on 30.04.1998), which includes polysorb and is distinguished by the fact that it additionally contains trypsin or chymopsin and ethonium in the following ratio of components, wt.%:

[0004] Polysorb 96-99

[0005] Trypsin or chymopsin 0.5-2.5

[0006] Ethonium 0.5-2.5.

[0007] The disadvantages of the known analogue are the insufficient effectiveness of the product, limited functionality, and inconvenience of use, which are due to the composition of the known analogue, in particular, the physical and chemical properties of the components included in its composition.

[0008] Despite the fact that Polysorb, which is part of the known analogue, is safe for health and has a high speed of action, it cannot be used for clean granulating and aseptic wounds, which is well known for contraindications to its use and narrows the functionality of the known analogue. In addition, the high content of Polysorb, which consists of colloidal silicon dioxide, makes the known analogue loose and gives it high dust-forming ability and low bulk density, which leads to inconvenience in using the known analogue, in particular, its spraying and unwanted loss during use, as well as to reduced efficiency of the known analogue due to its insufficient penetration into the affected tissues.

[0009] At the same time, trypsin and chymopsin, which are part of the known analogue, when they come into contact with affected tissues, can lead to local side effects, such as burning, redness and itching of the treated affected tissues. A general allergic reaction associated with the absorption of proteolysis products of necrotic tissues is possible. In addition, the production of trypsin and chymopsin is a complex and expensive process, which accordingly increases the cost of the known analogue.

[0010] The presence of etonium in the known analogue can cause a feeling of slight burning and pain, which in some cases require preliminary treatment of the wound surface with a local anesthetic solution. Some patients may experience increased sensitivity, which manifests itself in skin rashes, urticaria, and edema.

[0011] Also known is a wound-healing preparation (patent for invention UA ​​32088 C2, IPC A61K3 1 / 14, A61K3 1 / 695, A61P17 / 02, published on 15.07.2004), which contains polymethylsiloxane with a medicinal product immobilized thereon, and additionally contains highly dispersed silicon dioxide, and as a medicinal product - a diquaternary ammonium compound in the following ratio of components, wt.%: polymethylsiloxane 23.5 - 75.0 highly dispersed silicon dioxide 22.5 -75.0 diquaternary ammonium compound 1.5 - 2.5. The disadvantages of the known analogue are the insufficient effectiveness of the drug, limited functionality, and inconvenience of use, which are due to the composition of the known analogue, in particular, the physical and chemical properties of the components that make up its composition.

[0012] Polymethylsiloxane (methylsilicic acid xerogel), which is part of the well-known analogue, despite its ability to absorb hydrophobic organic substances and metabolites of medium molecular weight, does not absorb toxic inorganic compounds and heavy metal ions.

[0013] In addition, the known analogue contains in its composition a diquaternary ammonium compound, such as ethonium or decamethoxin, which, when used with the known analogue, can cause the negative effects described above, which creates inconvenience for the patient.

[0014] The closest analogue of the claimed invention is a powder composition (invention application US 20210106531 A1, IPC A61K 9 / 14, A61K 33 / 00, A61K 45 / 06, A61L 15 / 18, A61L 15 / 45, published on 15.04.2021), which includes highly dispersed silica, hydrophobic silica, a cationic surfactant, in the following ratio, wt.%:

[0015] Highly dispersed silica 21-75

[0016] Hydrophobic silica 16-70

[0017] Cationic surfactant 0.1-4.

[0018] The disadvantages of the closest analogue are the insufficient effectiveness of the composition, limited functionality, inconvenience of use, which are due to the composition of the known analogue, in particular, the percentage ratio of its components. The percentage ratio and composition of the closest analogue determine its looseness, low density and increased dust-forming ability, which reduces its effectiveness, since it prevents the complete coverage of the affected tissues with a dense layer of the composition, and also leads to undesirable loss of the composition during its packaging in conditions of mass production and clinical use due to spraying of the closest analogue in the air.

[0019] At the same time, the percentage ratio and composition of the closest analogue do not provide a sufficiently effective hemostatic effect of the composition, which is necessary in many cases when using the closest analogue, and also do not provide sorption of low-molecular positively charged substances, such as biogenic amines, heavy metal ions, etc., which narrows the functionality of the closest analogue. In general, the range of toxic substances that can be exposed to the action of the closest analogue is not wide enough, which determines its low efficiency when used in disaster medicine, military medicine, etc., that is, in conditions where wounds are fresh, and their healing and treatment must occur under extreme conditions.

[0020] The technical objective of the claimed invention is to create a new composition for the treatment and healing of wounds, which has increased bulk density and thickness, a pronounced hemostatic effect and adsorption capacity in relation to an expanded range of pathogenic substances and microorganisms.

[0021] The solution to the technical problem is achieved in that the composition for the treatment and healing of wounds, which includes at least highly dispersed silica, hydrophobic silica, a cationic surfactant, according to the proposal, includes a substance from the group of aluminosilicates, and contains components in the following ratio, wt.%: Highly dispersed silica 26-74

[0022] Hydrophobic silica 18-55

[0023] Cationic surfactant 0.5-2.5

[0024] A substance from the group of aluminosilicates 7.5-14.5

[0025] Additional biologically active components 0-2.

[0026] In this case, according to the proposal, highly dispersed silica is highly dispersed hydrophilic silica, such as Aerosil brand A-300.

[0027] Also, according to the proposal, the hydrophobic silica is a highly dispersed hydrophobic silica, such as Aerosil brand AM-1-300 or Aerosil R972 Pharma, or micronized polymethylsiloxane.

[0028] However, according to the proposal, the cationic surfactant is decamethoxin or benzalkonium chloride, or benzethonium chloride, or cetylpyridinium chloride.

[0029] In addition, according to the proposal, a substance from the group of aluminosilicates is a natural or activated in any way zeolite, or synthetic zeolite, or kaolin, or montmorillonite.

[0030] In this case, according to the proposal, additional biologically active components are plant extracts, such as comfrey extract and / or marigold extract, and / or eucalyptus extract, such as chlorophyllipt.

[0031] Also, according to the proposal, the claimed composition is a powder-like agent.

[0032] The technical result is an increase in the effectiveness of the composition on the affected tissues, expansion of the functionality of the composition, provision of the possibility of sorption of low-molecular positively charged substances, such as biogenic amines and heavy metal ions, hydrophilic and hydrophobic tissue decomposition products, provision of an effective hemostatic effect of the composition, acceleration of rejection and melting of necrotic tissues with the avoidance of staged necrectomy during repeated surgical interventions and a decrease in the number of medical manipulations, including dressings, an increase in bulk density with a decrease in the dust-forming ability of the composition.

[0033] The cause-and-effect relationship between the essential features of the invention and the expected technical result is as follows.

[0034] The above technical result is achieved due to the content in the claimed composition of a substance from the aluminosilicate group, additional biologically active components, as well as due to the percentage ratio of components in the claimed composition as a whole.

[0035] The presence of a substance of the aluminosilicate group in the claimed composition allows increasing the thickness and bulk density of the claimed composition, compensating for the looseness and low density of highly dispersed silica and hydrophobic silica. Thus, during the manufacture and use of the claimed composition, there is no dust formation, which leads to its undesirable losses, and the claimed composition covers the wound surface with a dense layer, penetrating into all areas that require treatment and healing.

[0036] At the same time, the combination of a substance from the aluminosilicate group and other components in the stated ratio allows to impart to the stated composition a pronounced hemostatic function, consisting in adsorption with subsequent activation on the surface of highly dispersed silica and aluminosilicate of the trigger protein - the Hageman factor, which starts a cascade of reactions, as a result of which a thrombus is formed. In addition, the presence of additional biologically active components, such as plant extracts, adds antiseptic and wound-healing properties to the composition.

[0037] Necrolytic properties, along with dehydrating, sorbing and antimicrobial action, allow the claimed composition to be considered the drug of choice for patients with acute putrefactive infection in the first - purulent-necrotic - phase of the wound process. At the same time, due to the composition and properties of the components of the claimed composition, it is possible to expand the range of pathogenic substances that are sorbed, including both low- and high-molecular, hydrophilic and hydrophobic tissue decomposition products, and heavy metal ions.

[0038] The implementation of the claimed composition in such a way that it contains highly dispersed hydrophilic silica, such as Aerosil brand A-300, allows to increase its shelf life, as well as to achieve the maximum effect of highly dispersed hydrophilic silica as a sorbent due to the high specific sorption surface (in the range of 300-400 m 2 ) per 1 g of the main substance.

[0039] The implementation of the claimed composition such that it contains highly dispersed hydrophobic silica, such as Aerosil brand AM-1-300 or Aerosil R972 Pharma or micronized polymethylsiloxane allows to expand the range of substances that are sorbed from the wound content, due to low- and medium-molecular hydrophobic compounds. In addition, by increasing the content of highly dispersed hydrophobic silica in the composition, its hydrophilic properties can be reduced as a whole, which is essential for the treatment of wounds at the stage of granulation, when overdrying of the wound is unacceptable.

[0040] The implementation of the claimed composition such that it contains decamethoxin or benzalkonium chloride or benzethonium chloride or cetylpyridinium chloride allows for an optimal combination and enhancement of the bactericidal, fungicidal and preservative properties of the claimed composition, since the said antimicrobial properties of the said cationic surfactants allow for the neutralization of any infection in the affected tissues, which indicates the increased effectiveness of the claimed composition. In addition, the cationic surfactant in the composition acts as a hydrophilizer of the surface of hydrophobic silica, which promotes wetting of the composition with wound exudate.

[0041] The presence in the claimed composition of a substance from the aluminosilicate group, such as natural or activated by any method zeolite, or synthetic zeolite, or kaolin, or montmorillonite, is a preferred embodiment of the claimed composition, since it is the said substances from the aluminosilicate group that determine, respectively, the optimal bulk density, thickness, chemical reactivity, adsorption and hemostatic properties of the claimed composition in combination with safety for the patient's health. At the same time, the said aluminosilicates are available and have a low cost, and do not require complex and lengthy processing in the manufacture of the claimed composition, which reduces the cost of the composition as a whole.

[0042] The presence in the composition of the claimed composition of comfrey extract and / or marigold extract and / or eucalyptus extract, such as chlorophyllipt, makes it possible to increase the astringent, anti-inflammatory, antimicrobial, especially against staphylococci and streptococci, and enveloping effect of the claimed composition due to the glycosides, alkaloids and essential oils contained in the said plant extracts.

[0043] The powder form of the claimed composition allows for convenient and long-term storage of the claimed composition after the first opening of the bottle, as well as for the dosed distribution of the claimed composition over the surface of the affected tissues without interfering with the necessary surgical intervention, tamponade and other similar operations.

[0044] The claimed preparation is manufactured and used as follows. In a preferred embodiment of the claimed composition, the following stages are carried out for its manufacture. First, preliminary thermal degassing and sterilization of highly dispersed silica, for example, Aerosil brand A-300, is carried out at a temperature of 180 °C. Separately, thermal degassing and sterilization of aluminosilicate, such as zeolite or kaolin or montmorillonite, is carried out at a temperature of 180 °C. Simultaneously, mechanochemical immobilization of a cationic surfactant, such as decamethoxin or benzalkonium chloride or benzethonium chloride or cetylpyridinium chloride, is carried out on the surface of highly dispersed hydrophobic silica, for example, Aerosil brand AM-1-30, by jointly processing the said components of the claimed composition in a ball mill in the presence of 96% ethyl alcohol.Subsequently, the resulting semi-finished product is degassed, i.e., the alcohol residues are removed, at a temperature of 60-70 °C. After this, highly dispersed silica and the above-mentioned semi-finished product, which contains a cationic surfactant, are mixed in the required proportion in a ribbon mixer with the addition during mixing of the required amount of aluminosilicate, such as zeolite or kaolin or montmorillonite, and additional biologically active components, such as plant extracts.

[0045] The method of application of the claimed composition depends on the nature of the wound and diagnosis. Below are three examples of application of the claimed composition.

[0046] Example 1.

[0047] Patient L., 55 years old, noticed a painful tumor-like neoplasm in the area of ​​the right shoulder blade 5 days ago, which she treated herself with ointments. Upon examination, the body temperature reached 38.8 °C, pulse 94 beats / min, in the right shoulder blade area there is a painful infiltrate up to 10 cm in diameter, the skin above it is hyperemic, edematous, covered in the central part by multiple purulent passages. Results of a general blood test: leukocytes - 14.2 x 10 9 / l; Hb - 121 x 10 12 / l; ESR - 24 mm / hour.

[0048] The patient underwent a cruciform incision under intravenous general anesthesia, after which non-viable and infiltrated tissues were excised. The wound cavity was treated with antiseptic solutions, dried, sprinkled with a 3 mm thick layer of the stated composition, loosely tamponed with dry napkins; subsequent daily dressings were also performed in this manner. Already on the following day, the patient's body temperature returned to normal. After 3 days, the wound cleared up, its surface gradually filled with granulations, which made it possible to bring the edges of the wound together with strips of adhesive plaster and discharge the patient for outpatient treatment.

[0049] Example 2.

[0050] Patient M., 20 years old, was admitted with complaints of pain and the presence of an infiltrate around the anus. On examination, body temperature was 37.9 °C, pulse 88 beats / min, in the perianal area there was hyperemia of the skin without clear boundaries, a pear-shaped infiltrate, 2x5 cm, hot to the touch, painful, with softening in the center. Results of a general blood test: leukocytes - 13.3 x 10 9 / l; band neutrophils - 7%.

[0051] The patient was given spinal anesthesia, the infiltrate dome was opened, and up to 20 ml of pus was released. During the probe revision, the purulent tract followed intrasphincterically to the posterior crypt. Excision of the paraproctitis into the lumen of the rectum according to Gabriel was performed. Hemostasis. The wound cavity was treated with antiseptic solutions, dried, sprinkled with a 3 mm thick layer of the stated composition, loosely tamponed with dry napkins; subsequent daily dressings were also performed in this manner. The removed tissues were sent for histological and microbiological examination. Already on the following day, the patient's body temperature and the number of leukocytes decreased to normal values. After 3 days, the wound cleared up, the use of the stated composition was canceled as soon as the wound surface was filled with granulations. At the end of the observation, the wound healed with a flat scar.

[0052] Example 3.

[0053] Patient B., 58 years old, has been suffering from diabetes mellitus type 2 for 12 years. The patient complained of redness of the 1st toe of the left foot, the presence of a wound on the toe. During the examination of the patient, no disturbance of the main blood flow in the vessels of the lower extremities, manifestations of neuropathy, or a decrease in all types of sensation in the feet were found. X-ray did not reveal any traumatic or destructive lesions of the bones of the foot. General clinical blood tests are unchanged, blood glucose is 10.2 mmol / l. Upon examination, there is a chronic wound under hyperkeratosis on the plantar surface of the 1st toe of the left foot measuring 1.0 x 0.6 cm.

[0054] The wound was treated with an antiseptic solution, hyperkeratoses were surgically removed, and it turned out that the wound affected all layers of the skin down to the bone. The wound was sprinkled with a 3 mm thick layer of the stated composition, a sterile gauze bandage was applied on top. The patient was recommended to use shoes to unload the foot, as well as dressings - treat the wound and around the wound with a 7% povidone-iodine solution and sprinkle with a 3 mm thick layer of the stated composition, apply a sterile gauze bandage on top; perform the dressing 2 times a day. Upon examination on the second day, there is no hyperemia on the finger, granulation tissue in the wound covered the bone, the wound depth has decreased. Upon examination on the 7th day, there is no hyperemia on the finger, there are granulation tissues in the wound, the bone is not visualized, there is marginal epithelialization, the wound depth has decreased, the wound size is 0.8x0.5 cm.During examination on day 21, there is no hyperemia on the finger, there are granulation tissues in the wound, the bone is not visualized, there is active marginal epithelialization, the wound depth has significantly decreased, the wound size is 0.4 x 0.3 cm. During the control examination on day 35, the wound surface is completely epithelialized - the wound has healed. Thus, the use of the claimed composition allows you to quickly clean the wound bed from purulent-necrotic contents and prevents the spread of the purulent-necrotic process. Also, the use of the claimed composition effectively and quickly relieves inflammation in the wound. In the presence of a local infection, the claimed composition can be used without the use of systemic antibiotic therapy. The use of the claimed composition accelerates the appearance of granulation and epithelialization in chronic and trophic ulcers, which, together with the above factors, reduces the wound healing time.

[0055] A comparative analysis of the above technical solution with the closest analogue showed that the implementation of the set of essential features that characterize the proposed invention leads to the emergence of qualitatively new technical properties indicated above, the set of which was not previously established from the existing level of technology, which allows us to conclude that the proposed technical solution meets the criterion of “inventive step”.

[0056] In the existing sources of patent and scientific and technical information, no composition for the treatment and healing of wounds has been found that has the declared set of essential features, therefore the presented technical solution meets the criterion of “novelty”.

[0057] The proposed technical solution is industrially suitable, since it does not contain any elements or materials that cannot be reproduced at the current stage of technological development in industrial production conditions.

Claims

FORMULA 1. A composition for treating and healing wounds, which includes at least highly dispersed silica, hydrophobic silica, a cationic surfactant, which is characterized in that it includes a substance from the group of aluminosilicates, and contains components in the following ratio, wt.%: Highly dispersed silica 26-74 Hydrophobic silica 18-55 Cationic surfactant 0.5-2.5 A substance from the group of aluminosilicates 7.5-14.5 Additional biologically active components 0-2.

2. A composition for treating and healing wounds according to item 1, which is characterized in that the highly dispersed silica is highly dispersed hydrophilic silica, such as Aerosil brand A-300.

3. A composition for treating and healing wounds according to claim 1, which is characterized in that the hydrophobic silica is a highly dispersed hydrophobic silica, such as Aerosil brand AM-1-300 or Aerosil R972 Pharma, or micronized polymethyl siloxane.

4. A composition for treating and healing wounds according to claim 1, which is characterized in that the cationic surfactant is decamethoxin or benzalkonium chloride, or benzethonium chloride, or cetylpyridinium chloride.

5. A composition for treating and healing wounds according to claim 1, which is characterized in that the substance from the aluminosilicate group is a natural or any way activated zeolite, or synthetic zeolite, or kaolin, or montmorillonite.

6. A composition for treating and healing wounds according to claim 1, which is characterized in that the additional biologically active components are plant extracts, such as comfrey extract and / or marigold extract, and / or eucalyptus extract, such as chlorophyllipt.

7. A composition for treating and healing wounds according to item 1, which is characterized in that it is a powder-like agent.