Medical wound care composition based on oligomeric hyaluronic acid and application thereof

Abstract

The invention discloses a medical wound care composition based on oligomeric hyaluronic acid and application of the medical wound care composition. The medical wound nursing composition can rapidly form a compact protective film on the surface of skin or mucosa, effectively isolate invasion of external substances and reduce irritation and damage of the environment to the skin, the formed film can continuously keep stability for a long time and provide continuous protection, the risk of re-injury of small wounds is reduced, and the wound nursing composition has the advantages of being safe and reliable. The device can be used for auxiliary treatment of wounds, burns, postoperative nursing and various skin diseases, and has wide clinical applicability.

Description

Technical Field

[0001] The present invention relates to the field of biomedical engineering, and in particular to a biomolecule-based medical wound care composition, a preparation method thereof, and uses thereof. Background Art

[0002] Wounds to the human skin or mucous membranes involve a process involving the reconstruction and regeneration of the extracellular matrix by a variety of cells and their secretory products. Skin wound healing involves four distinct phases: hemostasis, inflammation, proliferation, and remodeling or reconstruction. The hemostasis phase of wound healing begins immediately after injury and is characterized by vasoconstriction, platelet aggregation, degranulation, and fibrin clot formation. Specifically, contact with the exposed extracellular matrix at the site of injury causes platelets to release coagulation factors, leading to clot formation. Furthermore, contact also causes platelets to release proinflammatory cytokines and growth factors, such as transforming growth factor, platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, and insulin-like growth factor. These factors activate and attract neutrophils and macrophages, triggering the next phase of wound healing: inflammation. During the hemostasis phase, bacteria, viruses, and other foreign matter can easily enter the body through the rupture, leading to various infections. Therefore, a protective film is formed at the wound site to enhance the surface barrier function. Furthermore, during this other phase of wound healing, there is a need to prevent direct contact with the outside world.

[0003] Various similar products have been reported. For example, Chinese patent application CN105749333A discloses a hyaluronic acid medical dressing and its preparation method. The dressing uses hyaluronic acid of different molecular weights and adds hydroquinone. Their combined use has a synergistic effect, can deeply penetrate the skin, promote wound healing, and have an anti-inflammatory effect. It can also promote the metabolism of human proteins, fats, and carbohydrates, stimulate the growth of epithelial cells, and is particularly suitable for wound repair of skin and mucous membranes. However, the liquid dressing is in the form of a liquid dressing, and the ingredients enter the skin to work, rather than acting on the skin surface. Moreover, the liquid dressing is inconvenient to use and is not suitable for use at the beginning of a wound, especially in the hemostasis stage.

[0004] In addition, Chinese patent application CN 112156234A discloses a hyaluronic acid film and its preparation method and application, which includes a cycloaddition reaction in a mixed system of a hyaluronic acid derivative M and a hyaluronic acid derivative F to obtain a hyaluronic acid pretreatment conjugate; a photoinitiator is added to the obtained hyaluronic acid pretreatment conjugate, and the film is cast in a mold, irradiated with light to undergo a photocrosslinking reaction, and then freeze-dried or air-dried to obtain the hyaluronic acid film. However, the formation of this film involves the use of a crosslinking agent and requires light to undergo a crosslinking reaction, making it unsuitable for wound care.

[0005] The information in the background technology is only intended to illustrate the general background of the invention and should not be regarded as an admission or any form of suggestion that this information constitutes the prior art known to a person skilled in the art. Summary of the Invention

[0006] In order to address at least some of the technical problems in the prior art, the present invention provides a medical wound care composition based on oligomeric hyaluronic acid, and its preparation method and use. Specifically, the present invention includes the following contents.

[0007] In a first aspect of the present invention, a medical wound care composition based on oligomeric hyaluronic acid is provided, which comprises 0.5-5 parts by weight of cross-linked polyacrylic acid, 3-10 parts by weight of glycerol, 0.5-5 parts by weight of oligomeric hyaluronic acid or its salt, 0.1-1 parts by weight of a thickener, and 0.1-1 parts by weight of triethanolamine.

[0008] In certain embodiments, according to the medical wound care composition based on oligomeric hyaluronic acid of the first aspect, the molecular weight of the oligomeric hyaluronic acid is 1×10 3 - 9×10 3 Da range, the molecular weight of the cross-linked polyacrylic acid is 5×10 5 - 3×10 6 In a wide range.

[0009] In certain embodiments, the medical wound care composition based on oligomeric hyaluronic acid according to the first aspect further comprises phenoxyethanol and / or vitamins.

[0010] In certain embodiments, according to the medical wound care composition based on oligomeric hyaluronic acid of the first aspect, the oligomeric hyaluronic acid is prepared by a method comprising the following steps: (a) treating a hyaluronic acid raw material in an organic solvent under ultrasound until the molecular weight is reduced; (b) adding acetyl chloride to the treated solution and further sonicating until dissolved to obtain a solution; and (c) adding water to the solution until a solid is obtained, and isolating the solid.

[0011] In certain embodiments, according to the oligomeric hyaluronic acid-based medical wound care composition of the first aspect, the ultrasonic conditions of step (a) or (b) include ultrasound performed using an ultrasonic frequency of 800 kHz to 1.5 MHz.

[0012] In certain embodiments, according to the medical wound care composition based on oligomeric hyaluronic acid of the first aspect, the organic solvent is selected from at least one of the group consisting of formamide, dimethylformamide and acetamide.

[0013] In certain embodiments, according to the medical wound care composition based on oligomeric hyaluronic acid of the first aspect, wherein the ultrasonic treatment time in step (a) is more than 20 hours; or The ultrasonic treatment time in step (a) is from 15 hours to less than 20 hours, and the method further comprises the step of (d) adding alkali solution to the solid of step (c) to dissolve the solid, and further treating the solid with ultrasound.

[0014] The second aspect of the present invention provides a medical device comprising the medical wound care composition based on oligomeric hyaluronic acid according to the first aspect of the present invention and a container.

[0015] In certain embodiments, according to the medical device of the second aspect, the container comprises a syringe assembly, an ointment tube, or a plastic bottle.

[0016] The third aspect of the present invention provides the use of the medical wound care composition based on oligomeric hyaluronic acid described in the first aspect, wherein the use includes forming a physical barrier dense protective film on the wound surface.

[0017] The medical wound care composition of the present invention can quickly form a dense protective film on the surface of the skin or mucous membrane, effectively isolating the invasion of external substances and reducing environmental irritation and damage to the skin. The formed film can maintain stability for a long time, providing continuous protection and reducing the risk of re-injury to small wounds.

[0018] The exemplary medical wound care composition of the present invention is formulated as an ointment. Its unique physical properties prevent it from penetrating the skin, allowing its ingredients to exert their local effects on the surface. This property allows the ointment to maintain a high concentration on the skin surface, providing more effective moisturizing and protection. Furthermore, by preventing penetration, the risk of harmful ingredients entering the bloodstream is reduced, improving safety and minimizing the potential for side effects.

[0019] The medical wound care composition of the present invention utilizes a natural hyaluronic acid component, exhibiting excellent skin compatibility and suitability for all skin types, particularly sensitive skin. It effectively prevents allergic and irritant reactions, exhibits excellent biocompatibility, and exhibits minimal allergenic properties. Furthermore, the resulting film has a restorative effect, helping to maintain local moisture, optimize the wound healing environment, and promote skin regeneration, making it suitable for adjunctive treatment of minor skin injuries and inflammation. Furthermore, the film formation can alleviate skin discomfort, reduce pain and burning sensations, and provide patients with a more comfortable experience.

[0020] The medical wound care composition of the present invention can be used for small-area wounds, burns, postoperative care, and the like, as an auxiliary treatment for various skin diseases, and has wide clinical applicability. DETAILED DESCRIPTION

[0021] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0022] It should be understood that the terms described in the present invention are only for describing particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges in the present invention, it should be understood that the upper and lower limits of the ranges and each intermediate value therebetween are specifically disclosed. Each smaller range between any stated value or intermediate value within a stated range and any other stated value or intermediate value within the stated range is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0023] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0024] The terms "wound" and "wound" are used interchangeably herein and have the same meaning, referring to any breakage or damage to the epidermis or mucous membrane caused by any reason. These include chronic wounds, such as ulcers caused by various reasons, as well as acute wounds, particularly open wounds, examples of which include but are not limited to cuts, scratches, abrasions, lacerations, avulsions, puncture wounds, excision wounds, infected wounds, ischemic wounds, radiation poisoning wounds, surgical wounds, or burns (e.g., thermal burns, chemical burns, radiation burns). The wound of the present invention particularly refers to a small wound.

[0025] The term "care" herein refers to the function or effect of forming a protective layer on the exposed surface of the wound, thereby physically isolating or providing a barrier between the wound and the outside world.

[0026] The terms "protective layer" and "protective film" are used interchangeably herein and have the same meaning, referring to a membrane-like structure formed on the wound surface that is capable of contacting and adhering to the epidermis or surface, such as the skin, with a specific bonding force. The protective layer is strong enough to adhere to the wound surface without cracking or breaking.

[0027] The present invention adopts oligomeric hyaluronic acid to enhance the strength of the cross-linked polyacrylic acid film-forming material, thereby realizing physical isolation or barrier effect after forming a protective film on the wound surface, thereby achieving the purpose of medical wound care.

[0028] In the present invention, cross-linked polyacrylic acid is used as a film-forming material, generally referring to a high molecular polymer formed by cross-linking acrylic acid or an acrylate with an allyl ether compound (e.g., allyl sucrose or pentaerythritol ether, etc.). Such cross-linked polyacrylic acid is highly hydrophilic and can absorb water and swell. Due to the structural characteristics of the long molecular chain, it is closely entangled with each other in the solvent. Therefore, it is often used as a thickener or suspending agent. When the solvent evaporates, it is easy to form a gel, but the traditional gel strength formed by the cross-linked polyacrylic acid is relatively weak. When applied to the wound surface, due to insufficient strength, it cannot form a membrane structure sufficient to achieve the purpose of protection.

[0029] In the present invention, the molecular weight of the cross-linked polyacrylic acid is generally 5×10 6 - 4×10 7 Da, preferably 1×10 7 -4×10 7 Da, more preferably 2×10 7 - 4×10 7 Da et al.

[0030] In the present invention, the amount of cross-linked polyacrylic acid used is generally 0.5-5 parts by weight, preferably 0.7-4 parts by weight, and more preferably 1-3 parts by weight. If the amount is too high, the strength of the protective film formed tends to decrease, and the viscosity of the composition is too high, making it difficult to use. On the other hand, if the amount is too low, the film-forming properties of the resulting composition tend to deteriorate.

[0031] In the present invention, oligomeric hyaluronic acid refers to oligosaccharides constituting hyaluronic acid in the range of 5-30 sugar monomers, and its molecular weight is generally less than 10000Da, preferably with a molecular weight of 1×10 3 - 9×10 3 Da range, more preferably the molecular weight is 3×10 3 - 8×10 3 Large range.

[0032] The oligomeric hyaluronic acid of the present invention is used as a material to enhance the strength of the protective layer. Due to its extremely low molecular weight, oligomeric hyaluronic acid is believed to easily penetrate the skin and achieve a moisturizing effect. However, the present invention has discovered that when combined with cross-linked polyacrylic acid of a specific molecular weight to form a solution, due to its low molecular weight, it easily enters the long-chain molecular structure of the cross-linked polyacrylic acid, and the resulting film structure has significantly improved strength as the solvent evaporates. The reasons for this are speculated to be the following two aspects: 1. Physical interactions between high- and low-molecular-weight molecules. The cross-linked polyacrylic acid of the present invention is a high-molecular-weight polymer with a relatively long chain structure, while the oligomeric hyaluronic acid of the present invention has a relatively short molecular weight and a chain structure, consisting of only 5-30 sugar monomers. Hyaluronic acid can be randomly dispersed into the spaces between or within the long chains of multiple cross-linked polyacrylic acids, thereby promoting bonding between the molecules.

[0033] 2. Chemical interaction between the two molecules. Cross-linked polyacrylic acid is a highly hydrophilic molecule, with an acid group content of 52-68%. Oligomeric hyaluronic acid, on the other hand, contains a higher number of hydroxyl groups. When the small oligomeric hyaluronic acid molecules are dispersed within the long-chain cross-linked polyacrylic acid molecules, the chemical bonding or non-covalent bonding between the acid groups and the hydroxyl groups creates a protective film with increased strength. This strength is significantly greater than that of simple cross-linked polyacrylic acid gel or low- or high-molecular-weight hyaluronic acid, achieving the high strength required for wound protection.

[0034] In the present invention, the oligomeric hyaluronic acid used as the strength enhancer may also be an oligomeric hyaluronate, which is a compound formed by at least one carboxyl group of at least one hyaluronic acid in the oligomeric hyaluronic acid and a metal salt ion. Examples of the metal salt ion include alkali metal salt ions such as sodium, potassium, and lithium; and alkaline earth metal salt ions such as calcium and magnesium.

[0035] In the present invention, the consumption of oligomeric hyaluronic acid or its salt is generally 0.5-5 weight portion, preferably 1-4 weight portion, more preferably 2-3 weight portion. If the consumption is too high, then may be due to overreaction with cross-linked polyacrylic acid, such as the hydroxyl group of oligomeric hyaluronic acid reacts with the acid group of redundant cross-linked polyacrylic acid, and affects the combination between cross-linked polyacrylic acid, and then affects film-forming property. On the other hand, if the consumption is too low, then will adversely affect the intensity of the protective film obtained. In the present invention, the consumption of oligomeric hyaluronic acid or its salt is too high or too low and not only includes that the concentration is too high or too low, but also includes that it is too high or too low relative to the consumption of cross-linked polyacrylic acid. Normally, the consumption of oligomeric hyaluronic acid or its salt and cross-linked polyacrylic acid is based on the ratio in the range of 1:1 to 5:1 by weight.

[0036] In the present invention, the oligomeric hyaluronic acid has an extremely low molecular weight, which is much lower than that of conventional low-molecular-weight hyaluronic acid, i.e., the molecular weight is usually above 10 KDa, or even above 100 KDa. The oligomeric hyaluronic acid can be purchased from the market or obtained by any other method.

[0037] In the present invention, an exemplary method for obtaining oligomeric hyaluronic acid includes: (a) treating a hyaluronic acid raw material in an organic solvent under ultrasound until the molecular weight is reduced; (b) adding acetyl chloride to the treated solution and further sonicating until dissolved to obtain a solution; and (c) adding water to the solution until a solid is obtained, and isolating the solid.

[0038] In the present invention, the ultrasonic conditions of step (a) or (b) include using an ultrasonic frequency of 800kHz to 1.5MHz to carry out ultrasound. In certain embodiments, the ultrasonic treatment time is more than 20 hours in step (a). In other embodiments, the ultrasonic treatment time is more than 15 hours to less than 20 hours in step (a), and further includes (d) adding alkali solution to the solid of step (c) to dissolve the solid, and further treating with ultrasound.

[0039] In the present invention, hyaluronic acid raw material refers to hyaluronic acid or its salt having a molecular weight greater than oligomeric, and its source is not particularly limited, preferably by bioengineering, such as hyaluronic acid or its salt obtained by microbial fermentation or hyaluronic acid or its salt obtained by artificial synthesis, also including hyaluronic acid or its salt further processed or processed from the above-mentioned sources. Such treatment includes enzymolysis, chemical decomposition, ultrasonic treatment, etc. Also preferably, the hyaluronic acid raw material herein is extracted from animal tissue, and examples of animal tissue include cockscomb, umbilical cord, pigskin, cowhide, fish or other animal skin, aorta, etc.

[0040] In the present invention, an organic solvent refers to a fat-soluble solvent as opposed to an aqueous solvent. The organic solvent herein preferably refers to a solvent that is free of water. Free of water means a water content of less than 0.02%, preferably less than 0.005%. The organic solvent is preferably a weakly basic organic solvent, particularly a small molecule amide solvent, examples of which include substituted or unsubstituted formamide, acetamide, and propionamide. Examples of substituted formamides include methylformamide, such as dimethylformamide.

[0041] In the present invention, ultrasound refers to a treatment method that uses a high-frequency, high-power ultrasonic generator to generate ultrasonic waves to irradiate the target object. Ultrasonic degradation of hyaluronic acid or its salts is a physical degradation method. However, traditional ultrasonic degradation of hyaluronic acid has a molecular weight limit and the molecular weight is still relatively large.

[0042] In the present invention, glycerin is used as a moisturizing agent in an amount of generally 3-10 parts by weight, preferably 3-8 parts by weight, and more preferably 4-6 parts by weight.

[0043] The composition of the present invention also includes a thickener, which is generally used in an amount of 0.1-1 parts by weight, preferably 0.2-0.8 parts by weight, and more preferably 0.4-0.6 parts by weight. The thickener is not limited, and examples thereof include but are not limited to carboxymethyl cellulose.

[0044] The composition of the present invention further comprises triethanolamine, which is used to adjust the pH of the composition or the formed film to a value suitable for the skin. The amount of triethanolamine used varies depending on the formulation of the composition, particularly the amount of cross-linked polyacrylic acid, etc. Exemplary amounts are 0.1-1 parts by weight, such as 0.2 parts by weight, 0.3 parts by weight, 0.4 parts by weight, 0.5 parts by weight, 0.6 parts by weight, 0.7 parts by weight, 0.8 parts by weight, 0.9 parts by weight, and 1.0 parts by weight.

[0045] The composition of the present invention further comprises a solvent, which is usually an aqueous solvent. The aqueous solvent usually does not contain salt components, preferably pure water or deionized water.

[0046] The composition of the present invention may further optionally include phenoxyethanol, which is generally used in an amount of 0.1-1 part by weight, preferably 0.2-0.8 part by weight, and more preferably 0.3-0.6 part by weight.

[0047] The composition of the present invention may also optionally include vitamins, which are generally used in an amount of 0.1-1 parts by weight, preferably 0.2-0.8 parts by weight, and more preferably 0.3-0.6 parts by weight. Examples of vitamins are not limited and include, but are not limited to, B vitamins, such as vitamin B3.

[0048] The composition of the present invention generally does not contain any other ingredients besides the essential and optional ingredients mentioned above.

[0049] Example 1 1. Preparation of Oligomeric Hyaluronate 1. Disperse 10 g of hyaluronate solid powder (loss on drying less than 5%) in 200 ml of formamide under 1 MHz ultrasound to form a suspension, and further ultrasonicate for 25 hours.

[0050] 2. Under an inert atmosphere, mix acetyl chloride and formamide in equal volumes, then slowly add 50 mL of the mixture to the suspension in step 1 and treat at 70-90°C under 1 MHz ultrasound until completely dissolved.

[0051] 3. Add 2 L of water to the solution, stir thoroughly, and separate the white solid. Wash with water until neutral, and dry. The molecular weight of the solid is 6348 Da, which is used for subsequent product preparation.

[0052] 2. Preparation of Ointment Composition Medical sodium hyaluronate ointment was prepared according to the following formula: Cross-linked polyacrylic acid (Carbopol ® , 20,000KDa) 1%; Glycerol 5%; Sodium oligomeric hyaluronate 1%; Carboxymethyl cellulose 0.2%; Triethanolamine 0.5%; Phenoxyethanol 0.2%; Vitamin B3 0.1%; The balance is water.

[0053] Three injection sizes (1g, 2g, and 3g) are prepared based on the above formula. Each size consists of a prefilled syringe assembly and ointment. The product is sterilized by irradiation and is provided sterile.

[0054] Example 2 1. Preparation of Oligomeric Hyaluronate 1. Disperse 10 g of hyaluronate solid powder (loss on drying less than 5%) in 200 ml of formamide under 1 MHz ultrasound to form a suspension, and further ultrasonicate for 25 hours.

[0055] 2. Under an inert atmosphere, mix acetyl chloride and formamide in equal volumes, then slowly add 50 mL of the mixture to the suspension in step 1 and treat at 70-90°C under 1 MHz ultrasound until completely dissolved.

[0056] 3. Add 2 L of water to the solution, stir thoroughly, and separate the white solid. Wash with water until neutral, and dry. The molecular weight of the solid is 6348 Da, which is used for subsequent product preparation.

[0057] 2. Preparation of Ointment Composition Medical sodium hyaluronate ointment was prepared according to the following formula: Cross-linked polyacrylic acid (Carbopol ® , 20,000KDa) 1%; Glycerol 5%; Sodium oligomeric hyaluronate 1%; Carboxymethyl cellulose 0.2%; Triethanolamine 0.5%; Phenoxyethanol 0.2%; Vitamin B3 0.1%; The balance is water.

[0058] According to the above formula, three sizes of extruded products (10g, 15g, 20g, and 30g) are prepared. Each of them consists of an ointment tube and ointment, or a plastic bottle (with a pump head) and ointment. The product is sterilized by irradiation and is provided sterile.

[0059] Comparative Example 1 1. Preparation of Oligomeric Hyaluronate 1. Disperse 10 g of hyaluronate solid powder (loss on drying less than 5%) in 200 ml of formamide under 1 MHz ultrasound to form a suspension, and further ultrasonicate for 25 hours.

[0060] 2. Under an inert atmosphere, mix acetyl chloride and formamide in equal volumes, then slowly add 50 mL of the mixture to the suspension in step 1 and treat at 70-90°C under 1 MHz ultrasound until completely dissolved.

[0061] 3. Add 2 L of water to the solution, stir thoroughly, and separate the white solid. Wash with water until neutral, and dry. The molecular weight of the solid is 6348 Da, which is used for subsequent product preparation.

[0062] 2. Preparation of Ointment Composition Medical sodium hyaluronate ointment (model 1g) was prepared according to the following formula: Cross-linked polyacrylic acid (Carbopol ® , 20,000KDa) 5%; Glycerol 5%; Sodium oligomeric hyaluronate 1%; Carboxymethyl cellulose 0.2%; Triethanolamine 2%; Phenoxyethanol 0.2%; Vitamin B3 0.1%; The balance is water.

[0063] The product is sterilized by irradiation and provided sterile.

[0064] Comparative Example 2 Medical sodium hyaluronate ointment (model 1g) was prepared according to the following formula: Cross-linked polyacrylic acid (Carbopol ® , 20,000KDa) 1%; Glycerol 5%; Carboxymethyl cellulose 0.2%; Triethanolamine 0.5%; Phenoxyethanol 0.2%; Vitamin B3 0.1%; The balance is water.

[0065] The product is sterilized by irradiation and provided sterile.

[0066] Comparative Example 3 Medical sodium hyaluronate ointment (model 1g) was prepared according to the following formula: Cross-linked polyacrylic acid (Carbopol ® , 20,000KDa) 1%; Glycerol 5%; Sodium hyaluronate (50KDa) 1%; Carboxymethyl cellulose 0.2%; Triethanolamine 0.5%; Phenoxyethanol 0.2%; Vitamin B3 0.1%; The balance is water.

[0067] The product is sterilized by irradiation and provided sterile.

[0068] Comparative Example 4 Medical sodium hyaluronate ointment (model 1g) was prepared according to the following formula: Cross-linked polyacrylic acid (Carbopol ® , 20,000KDa) 1%; Glycerol 5%; Sodium oligomeric hyaluronate (same as Comparative Example 1) 6%; Carboxymethyl cellulose 0.2%; Triethanolamine 0.5%; Phenoxyethanol 0.2%; Vitamin B3 0.1%; The balance is water.

[0069] The product is sterilized by irradiation and provided sterile.

[0070] Test Case 1. Properties and film-forming properties Visually observe the properties of the composition. Take the products obtained in the examples and comparative examples (about 0.5 g each) and apply them directly to the clean skin surface (about 2 cm 2 Size), apply evenly, and after 1 hour, use tweezers to pick up the film from one side to check the film forming properties. The standards are as follows: Advantages: It can be lifted and the complete membrane structure can be slowly peeled off from the skin surface; Good: The membrane structure is intact when peeled off more than 50% from the skin surface, but it is damaged when peeled off further, and is not a complete membrane structure; Poor: Cannot be lifted, or can be lifted but the membrane structure portion removed is less than 50%.

[0071] 2. Transepidermal Water Loss Test Apply the ointment directly to clean skin, spreading evenly three times daily. Measure transepidermal water loss using a Tewameter before use, two days after use, five days after use, and ten days after use. Measurements are based on the diffusion law, as shown below: ; Where: A-surface area (m 2), M – water loss (g), T – time (h), D – diffusion constant (±0.0877 g / m•h•mm Hg), p – atmospheric vapor pressure (mm Hg), and x – distance from the skin surface to the measurement point (m).

[0072] Diffusion rate dm / dt represents the volume of air transported per cm in a period of time. 2 The density gradient is directly proportional to the area A and the change in concentration per unit distance dp / dx. This law is valid only within the uniform diffusion zone approximately formed by a hollow cylinder. The resulting density gradient is indirectly measured by two pairs of sensors (temperature and relative humidity) and analyzed by a microprocessor. The temperature and humidity sensors, as well as the measurement electronics and calibration data, are located inside the probe. The probe's measuring head is a narrow hollow cylinder (10 mm diameter, 20 mm height) to minimize the effects of air turbulence inside the probe.

[0073] 3. Mechanical properties test To more accurately compare the film strengths of different products, a simulation test was conducted using the following method: Each formulation was applied to a surface to create a membrane structure measuring 50 mm x 4 mm x 3 mm. The tensile strength was measured using a Shimadzu AGS-X at a speed of 10 cm / minute. Three measurements were taken for each product, and the average result was used as the final result.

[0074] 4. Test Results The test results are shown in Table 1.

[0075] Table 1 Although the present invention has been described with reference to exemplary embodiments, it should be understood that the invention is not limited to the disclosed exemplary embodiments. Various modifications and variations may be made to the exemplary embodiments of the present specification without departing from the scope or spirit of the present invention. The scope of the claims is to be given the broadest interpretation so as to encompass all such modifications and equivalent structures and functions.

Claims

1. A medical wound care composition based on oligomeric hyaluronic acid, characterized in that: The invention comprises 0.5-5 parts by weight of cross-linked polyacrylic acid, 3-10 parts by weight of glycerol, 0.5-5 parts by weight of oligomeric hyaluronic acid or its salt, 0.1-1 parts by weight of thickener, and 0.1-1 parts by weight of triethanolamine; wherein the molecular weight of the oligomeric hyaluronic acid is 1×10 3 - 9×10 3 Da range, the molecular weight of the cross-linked polyacrylic acid is 5×10 5 - 3×10 6 In a wide range.

2. The medical wound care composition based on oligomeric hyaluronic acid according to claim 1, characterized in that The invention further comprises 0.1-1 parts by weight of phenoxyethanol.

3. The medical wound care composition based on oligomeric hyaluronic acid according to claim 1, characterized in that It further comprises 0.1-1 parts by weight of vitamins.

4. The medical wound care composition based on oligomeric hyaluronic acid according to claim 1, characterized in that The oligomeric hyaluronic acid is prepared by a method comprising the following steps: (a) treating a hyaluronic acid raw material in an organic solvent under ultrasound until the molecular weight is reduced; (b) adding acetyl chloride to the treated solution and further sonicating until dissolved to obtain a solution; and (c) adding water to the solution until a solid is obtained, and isolating the solid.

5. The medical wound care composition based on oligomeric hyaluronic acid according to claim 4, characterized in that The ultrasonic conditions of step (a) or (b) include ultrasonication using an ultrasonic frequency of 800 kHz to 1.5 MHz.

6. The medical wound care composition based on oligomeric hyaluronic acid according to claim 4, wherein The organic solvent is at least one selected from the group consisting of formamide, dimethylformamide and acetamide.

7. The medical wound care composition based on oligomeric hyaluronic acid according to claim 4, characterized in that The ultrasonic treatment time in step (a) is more than 20 hours; or The ultrasonic treatment time in step (a) is from 15 hours to less than 20 hours, and the method further comprises the step of (d) adding alkali solution to the solid of step (c) to dissolve the solid, and further treating the solid with ultrasound.

8. A medical device, characterized in that: Comprising the medical wound care composition based on oligomeric hyaluronic acid according to any one of claims 1 to 7 and a container.

9. The medical device according to claim 8, characterized in that Such containers include syringe assemblies, ointment tubes, or plastic bottles.

10. The use of the medical wound care composition based on oligomeric hyaluronic acid according to any one of claims 1 to 7, characterized in that: The use includes forming a physical barrier dense protective film on the wound surface.

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