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

Abstract

This invention discloses a medical wound care composition based on oligomeric hyaluronic acid and its uses. The medical wound care composition of this invention can rapidly form a dense protective film on the skin or mucous membrane surface, effectively isolating the invasion of external substances, reducing environmental irritation and damage to the skin, and the formed film can maintain stability for a long time, providing continuous protection and reducing the risk of re-injury to small wounds. It can be used for trauma, burns, postoperative care, and as an adjunct treatment for various skin diseases, and has broad clinical applicability.

Description

Technical Field

[0001] This invention relates to the field of biomedical engineering, and more specifically to biomolecule-based medical wound care compositions, their preparation methods, and uses. Background Technology

[0002] Trauma to the human skin or mucous membranes is a process involving the reconstruction and regeneration of the extracellular matrix by various cells and their secretions. Skin wound healing comprises 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 clotting factors, leading to clot formation. Furthermore, contact also causes platelets to release pro-inflammatory 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, thus triggering the next phase of wound healing: the inflammation phase. During the hemostasis phase, bacteria, viruses, and other foreign substances can easily enter the body through the rupture, leading to various diseases. Therefore, a protective film needs to form at the wound site to enhance the surface barrier function. Additionally, there is a need to avoid direct contact with the external environment during other phases of wound healing.

[0003] Various similar products have been reported. For example, Chinese patent application CN105749333A discloses a hyaluronic acid medical dressing and its preparation method. This dressing uses a compound of hyaluronic acid with different molecular weights and adds hydroquinone. Their combined use has a synergistic effect, allowing it to penetrate deep into the skin, promote wound healing, and exert anti-inflammatory effects. It also promotes the metabolism of proteins, fats, and carbohydrates in the human body and stimulates the growth of epithelial cells, making it particularly suitable for the repair of skin and mucous membrane wounds. However, its form is a liquid dressing; the components exert their effects inside the skin rather than on the skin surface. Furthermore, using this liquid dressing is inconvenient and unsuitable for use at the beginning of a wound healing process, especially during the hemostasis phase.

[0004] Furthermore, Chinese patent application CN 112156234A discloses a hyaluronic acid membrane, its preparation method, and its application. This method involves a cycloaddition reaction in a mixture of hyaluronic acid derivatives M and F to obtain a hyaluronic acid pretreatment conjugate; adding a photoinitiator to the obtained hyaluronic acid pretreatment conjugate; casting the membrane in a mold; subjecting it to a photocrosslinking reaction under light; and then lyophilizing or air-drying to obtain the hyaluronic acid membrane. However, the formation of this membrane involves the use of a crosslinking agent and requires light exposure for the crosslinking reaction, making it unsuitable for wound care.

[0005] The information in the background section is merely intended to illustrate the general background of the invention and should not be construed as an admission or implication in any way that such information constitutes prior art known to those skilled in the art. Summary of the Invention

[0006] 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, a method for preparing the composition, and its uses. Specifically, the present invention includes the following:

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

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

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

[0010] In some embodiments, the medical wound care composition based on oligomeric hyaluronic acid according to the first aspect is wherein the oligomeric hyaluronic acid is prepared by a method comprising the steps of:

[0011] (a) Hyaluronic acid raw material is treated in an organic solvent under ultrasound until the molecular weight is reduced;

[0012] (b) Add acetyl chloride to the treatment solution and further sonicate until dissolved to obtain a solution; and

[0013] (c) Add water to the solution until a solid is obtained, and separate the solid.

[0014] In some embodiments, the medical wound care composition based on oligomeric hyaluronic acid according to the first aspect, wherein the ultrasound conditions of step (a) or (b) include ultrasound using an ultrasound frequency of 800 kHz to 1.5 MHz.

[0015] In some embodiments, the medical wound care composition based on oligomeric hyaluronic acid according to the first aspect, wherein the organic solvent is selected from at least one of the group consisting of formamide, dimethylformamide and acetamide.

[0016] In some embodiments, the medical wound care composition based on oligomeric hyaluronic acid according to the first aspect, wherein the ultrasonic treatment time in step (a) is 20 hours or more; or

[0017] The ultrasonic treatment time in step (a) is more than 15 hours and less than 20 hours, and further includes (d) adding an alkaline solution to the solid in step (c) to dissolve the solid, and further treating it with ultrasound.

[0018] A second aspect of the present invention provides a medical device comprising the medical wound care composition and container based on oligomeric hyaluronic acid as described in the first aspect of the present invention.

[0019] In some embodiments, the medical device according to the second aspect includes a container comprising a syringe assembly, an ointment tube, or a plastic bottle.

[0020] A third aspect of the 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 physically barrier dense protective film on the wound.

[0021] The medical wound care composition of the present invention can quickly form a dense protective film on the skin or mucous membrane surface, effectively isolating the invasion of external substances, reducing environmental irritation and damage to the skin, and the formed film can maintain stability for a long time, providing continuous protection and reducing the risk of re-injury to small wounds.

[0022] The exemplary medical wound care composition of this invention is prepared as an ointment. Its special physical properties prevent it from penetrating the skin, allowing the ingredients to exert a localized effect on the surface. This characteristic enables the ointment to maintain a high concentration on the skin surface, providing more effective moisturizing and protection. Simultaneously, by preventing penetration, the risk of harmful ingredients entering the bloodstream is reduced, improving safety and minimizing the possibility of side effects.

[0023] The medical wound care composition of this invention utilizes natural hyaluronic acid, which has good skin affinity and is suitable for all skin types, especially sensitive skin. It effectively prevents allergic and irritant reactions, exhibiting excellent biocompatibility and extremely low allergenicity. Furthermore, the formed film has a repairing effect, helping to maintain local humidity, optimizing the wound healing environment, and promoting skin regeneration. It is suitable for the adjunctive treatment of minor skin injuries and inflammation. Moreover, after film formation, it can relieve skin discomfort, reduce pain and burning sensations, and provide patients with a better comfort experience.

[0024] The medical wound care composition of the present invention can be used for small-area trauma, burns, postoperative care, and as an adjunct treatment for various skin diseases, and has wide clinical applicability. Detailed Implementation

[0025] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0026] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that the upper and lower limits of the range and each intermediate value between them are specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0027] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0028] The term "wound" in this document is used interchangeably with "incision" or "wound" and has the same meaning, referring to any break or injury to the epidermis or mucous membrane caused by any reason, including chronic wounds such as ulcers of various causes, as well as acute wounds, especially 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). In this invention, "wound" specifically refers to a small-area wound.

[0029] The term "nursing care" in this article refers to the function or role of forming a protective layer on the exposed surface of a wound, thereby physically isolating or creating a barrier between the wound and the outside world.

[0030] In this article, the terms "protective layer" and "protective membrane" are used interchangeably and have the same meaning: a membrane-like structure formed on a wound surface that can adhere to the epidermis or surface, such as the skin, with specific bonding forces. The protective layer has sufficient strength to adhere to the wound surface without cracking or breaking.

[0031] This invention uses oligomeric hyaluronic acid to enhance the strength of cross-linked polyacrylic acid film-forming materials, thereby achieving physical isolation or barrier function after a protective film is formed on the wound, thus achieving the purpose of medical wound care.

[0032] In this invention, cross-linked polyacrylic acid, used as a film-forming material, generally refers to a high molecular weight polymer formed by cross-linking acrylic acid or acrylate with allyl ether compounds (e.g., allyl sucrose or pentaerythritol ether). This type of cross-linked polyacrylic acid is highly hydrophilic and can swell by absorbing water. Due to its long molecular chain structure, it becomes tightly entangled in solvents. Therefore, it is often used as a thickener or suspending agent. It easily forms a gel after the solvent evaporates; however, the traditional gel formed by cross-linked polyacrylic acid is relatively weak, and when applied to wounds, its insufficient strength prevents the formation of a film structure sufficient for protection.

[0033] In this invention, the molecular weight of cross-linked polyacrylic acid is generally 5 × 10⁻⁶. 6 - 4×10 7 Between Da, 1×10 is preferred. 7 -4×10 7 Da, more preferably 2×10 7 - 4×10 7 Da et al.

[0034] In this 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 composition becomes too viscous, which is not conducive to its use. On the other hand, if the amount is too low, the film-forming properties of the resulting composition tend to deteriorate.

[0035] In this invention, oligomeric hyaluronic acid refers to oligosaccharides constituting hyaluronic acid with 5-30 sugar monomers, and a molecular weight generally below 10,000 Da, preferably 1 × 10⁻⁶. 3 - 9×10 3 The molecular weight is more preferably in the range of 3×10⁻⁶. 3 - 8×10 3 Da range.

[0036] The oligomeric hyaluronic acid of this invention serves as a material for enhancing the strength of the protective layer. Oligomeric hyaluronic acid is understood to easily penetrate the skin and achieve a moisturizing effect due to its extremely low molecular weight. However, this invention has discovered that when combined with cross-linked polyacrylic acid of a specific molecular weight to form a solution, the small molecular weight allows it to easily enter the long-chain molecular structure of the cross-linked polyacrylic acid, and the film structure formed as the solvent evaporates exhibits significantly improved strength. The reasons for this are speculated to be due to the following two aspects:

[0037] 1. Physical interaction between molecules of different molecular weights. The cross-linked polyacrylic acid of the present invention is a high molecular weight polymer with a long chain structure, while the oligomeric hyaluronic acid of the present invention has a short molecular weight and a short chain structure, consisting of only 5-30 sugar monomers. It can disperse randomly into the spaces between or inside the long chains of multiple cross-linked polyacrylic acids, thereby promoting the binding between molecules.

[0038] 2. Chemical interaction between the two molecules. Cross-linked polyacrylic acid is a highly hydrophilic molecule with an acid group content of 52-68%, while oligomeric hyaluronic acid molecules contain more hydroxyl groups. When small-molecule oligomeric hyaluronic acid disperses into the long-chain molecules of cross-linked polyacrylic acid, the chemical bonding or non-covalent bonding between the acid groups and hydroxyl groups results in a protective film with higher strength. This strength is significantly higher than that of simple cross-linked polyacrylic acid gel or low- or high-molecular-weight hyaluronic acid, achieving the high strength of the film required for wound protection.

[0039] In this invention, the oligomeric hyaluronic acid used as a strength enhancer can also be an oligomeric hyaluronic acid salt, 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 metal salt ions include alkali metal salt ions, such as sodium, potassium, and lithium; and alkaline earth metal salt ions, such as calcium and magnesium.

[0040] In this invention, the amount of oligomeric hyaluronic acid or its salt is generally 0.5-5 parts by weight, preferably 1-4 parts by weight, and more preferably 2-3 parts by weight. If the amount is too high, it may cause excessive reaction with the cross-linked polyacrylic acid, for example, the hydroxyl groups of the oligomeric hyaluronic acid reacting with the acid groups of the excess cross-linked polyacrylic acid, thus affecting the bonding between the cross-linked polyacrylic acids and consequently affecting film formation. On the other hand, if the amount is too low, it will adversely affect the strength of the resulting protective film. In this invention, excessive or insufficient use of oligomeric hyaluronic acid or its salt includes not only excessively high or low concentration, but also excessively high or low relative to the amount of cross-linked polyacrylic acid. Typically, the weight ratio of oligomeric hyaluronic acid or its salt to cross-linked polyacrylic acid is in the range of 1:1 to 5:1.

[0041] In this invention, the oligomeric hyaluronic acid has an extremely low molecular weight, far lower than that of conventional low-molecular-weight hyaluronic acid, typically exceeding 10 kDa, or even 100 kDa. Oligomeric hyaluronic acid can be obtained commercially or through any other means.

[0042] In this invention, an exemplary method for obtaining oligomeric hyaluronic acid includes:

[0043] (a) Hyaluronic acid raw material is treated in an organic solvent under ultrasound until the molecular weight is reduced;

[0044] (b) Add acetyl chloride to the treatment solution and further sonicate until dissolved to obtain a solution; and

[0045] (c) Add water to the solution until a solid is obtained, and separate the solid.

[0046] In this invention, the ultrasonic conditions in step (a) or (b) include ultrasonication using an ultrasonic frequency of 800 kHz to 1.5 MHz. In some embodiments, the ultrasonic treatment time in step (a) is 20 hours or more. In other embodiments, the ultrasonic treatment time in step (a) is 15 hours or more but less than 20 hours, and further includes (d) adding an alkaline solution to the solid from step (c) to dissolve the solid, followed by further ultrasonic treatment.

[0047] In this invention, hyaluronic acid raw material refers to hyaluronic acid or its salt with a molecular weight greater than oligomer. Its source is not particularly limited, but preferably it is hyaluronic acid or its salt obtained through bioengineering, such as microbial fermentation, or through artificial synthesis. It also includes degraded hyaluronic acid or its salt obtained through further processing or treatment of hyaluronic acid or its salt from the above sources. Such processing includes enzymatic hydrolysis, chemical decomposition, and ultrasonic treatment. More preferably, the hyaluronic acid raw material in this invention is extracted from animal tissues, examples of which include rooster combs, umbilical cords, pig skin, cowhide, fish skin, or other animal skins, aortas, etc.

[0048] In this invention, organic solvent refers to a fat-soluble solvent as opposed to an aqueous solvent. Preferably, the organic solvent referred to herein is an anhydrous solvent. Anhydrous means having 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 formamides, acetamides, and propionamides. Examples of substituted formamides include methylformamides, such as dimethylformamide.

[0049] In this 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 remains relatively large.

[0050] In this invention, glycerin is used as a moisturizer, and its dosage is generally 3-10 parts by weight, preferably 3-8 parts by weight, and more preferably 4-6 parts by weight.

[0051] 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 include, but are not limited to, carboxymethyl cellulose.

[0052] The compositions of the present invention further comprise triethanolamine for adjusting the pH of the composition or the formed film to a value suitable for the skin, the amount of which 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.

[0053] The compositions of the present invention also contain a solvent, which is typically an aqueous solvent and generally does not contain salt components. Preferably, it is pure water or deionized water.

[0054] The composition of the present invention may optionally include phenoxyethanol, 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 0.3-0.6 parts by weight.

[0055] The compositions of the present invention may optionally include vitamins, typically 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, but include, but are not limited to, B vitamins, such as vitamin B3.

[0056] The compositions of the present invention generally do not contain any other ingredients besides the essential and optional ingredients described above.

[0057] Example 1

[0058] I. Preparation of oligomeric hyaluronic acid salts

[0059] 1. Disperse 10g of hyaluronic acid salt solid powder (with drying loss of less than 5%) in 200ml of formamide under 1MHz ultrasound to form a suspension, and then further sonicate for 25 hours.

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

[0061] 3. Add 2L of water to the solution, stir thoroughly, separate the white solid, wash with water until neutral, and dry to obtain the final product. Its molecular weight was measured to be 6348 Da, and it will be used for subsequent product preparation.

[0062] II. Preparation of Ointment Compositions

[0063] Prepare medical sodium hyaluronate ointment according to the following formula:

[0064] Cross-linked polyacrylic acid (Carbopol) ® , 20,000KDa) 1%;

[0065] 5% glycerin;

[0066] Oligomeric sodium hyaluronate 1%;

[0067] Carboxymethyl cellulose 0.2%;

[0068] Triethanolamine 0.5%;

[0069] Phenoxyethanol 0.2%;

[0070] Vitamin B3 0.1%;

[0071] The remainder is water.

[0072] Three sizes of injectable products, 1g, 2g, and 3g, were prepared according to the above formula. Each product consists of a pre-filled syringe assembly and an ointment. The products are sterilized by irradiation and provided aseptically.

[0073] Example 2

[0074] I. Preparation of oligomeric hyaluronic acid salts

[0075] 1. Disperse 10g of hyaluronic acid salt solid powder (with drying loss of less than 5%) in 200ml of formamide under 1MHz ultrasound to form a suspension, and then further sonicate for 25 hours.

[0076] 2. Mix acetyl chloride and formamide in equal volume ratio under an inert atmosphere, then slowly add 50 mL of the mixture to the suspension in step 1, and treat with 1 MHz sonication at 70-90 °C until completely dissolved.

[0077] 3. Add 2L of water to the solution, stir thoroughly, separate the white solid, wash with water until neutral, and dry to obtain the final product. Its molecular weight was measured to be 6348 Da, and it will be used for subsequent product preparation.

[0078] II. Preparation of Ointment Compositions

[0079] Prepare medical sodium hyaluronate ointment according to the following formula:

[0080] Cross-linked polyacrylic acid (Carbopol) ® , 20,000KDa) 1%;

[0081] 5% glycerin;

[0082] Oligomeric sodium hyaluronate 1%;

[0083] Carboxymethyl cellulose 0.2%;

[0084] Triethanolamine 0.5%;

[0085] Phenoxyethanol 0.2%;

[0086] Vitamin B3 0.1%;

[0087] The remainder is water.

[0088] Three extrusion-type products in 10g, 15g, 20g, and 30g sizes are prepared according to the above formula. These products consist of an ointment tube and ointment, or a plastic bottle (with a pump head) and ointment, respectively. The products are sterilized by irradiation and provided aseptically.

[0089] Comparative Example 1

[0090] I. Preparation of oligomeric hyaluronic acid salts

[0091] 1. Disperse 10g of hyaluronic acid salt solid powder (with drying loss of less than 5%) in 200ml of formamide under 1MHz ultrasound to form a suspension, and then further sonicate for 25 hours.

[0092] 2. Mix acetyl chloride and formamide in equal volume ratio under an inert atmosphere, then slowly add 50 mL of the mixture to the suspension in step 1, and treat with 1 MHz sonication at 70-90 °C until completely dissolved.

[0093] 3. Add 2L of water to the solution, stir thoroughly, separate the white solid, wash with water until neutral, and dry to obtain the final product. Its molecular weight was measured to be 6348 Da, and it will be used for subsequent product preparation.

[0094] II. Preparation of Ointment Compositions

[0095] Prepare medical sodium hyaluronate ointment (1g size) according to the following formula:

[0096] Cross-linked polyacrylic acid (Carbopol) ® , 20,000KDa) 5%;

[0097] 5% glycerin;

[0098] Oligomeric sodium hyaluronate 1%;

[0099] Carboxymethyl cellulose 0.2%;

[0100] Triethanolamine 2%

[0101] Phenoxyethanol 0.2%;

[0102] Vitamin B3 0.1%;

[0103] The remainder is water.

[0104] The product is sterilized by irradiation and provided aseptically.

[0105] Comparative Example 2

[0106] Prepare medical sodium hyaluronate ointment (1g size) according to the following formula:

[0107] Cross-linked polyacrylic acid (Carbopol) ® , 20,000KDa) 1%;

[0108] 5% glycerin;

[0109] Carboxymethyl cellulose 0.2%;

[0110] Triethanolamine 0.5%;

[0111] Phenoxyethanol 0.2%;

[0112] Vitamin B3 0.1%;

[0113] The remainder is water.

[0114] The product is sterilized by irradiation and provided aseptically.

[0115] Comparative Example 3

[0116] Prepare medical sodium hyaluronate ointment (1g size) according to the following formula:

[0117] Cross-linked polyacrylic acid (Carbopol) ® , 20,000KDa) 1%;

[0118] 5% glycerin;

[0119] Sodium hyaluronate (50 kDa) 1%;

[0120] Carboxymethyl cellulose 0.2%;

[0121] Triethanolamine 0.5%;

[0122] Phenoxyethanol 0.2%;

[0123] Vitamin B3 0.1%;

[0124] The remainder is water.

[0125] The product is sterilized by irradiation and provided aseptically.

[0126] Comparative Example 4

[0127] Prepare medical sodium hyaluronate ointment (1g size) according to the following formula:

[0128] Cross-linked polyacrylic acid (Carbopol) ® , 20,000KDa) 1%;

[0129] 5% glycerin;

[0130] Oligomeric sodium hyaluronate (same as Comparative Example 1) 6%;

[0131] Carboxymethyl cellulose 0.2%;

[0132] Triethanolamine 0.5%;

[0133] Phenoxyethanol 0.2%;

[0134] Vitamin B3 0.1%;

[0135] The remainder is water.

[0136] The product is sterilized by irradiation and provided aseptically.

[0137] Test case

[0138] I. Properties and Film-forming Properties

[0139] Visually observe the properties of the composition. Apply approximately 0.5 g of the product obtained in the examples and comparative examples directly to a clean skin surface (approximately 2 cm²). 2 Apply evenly (size), and after 1 hour, use tweezers to lift it from one side to check the film formation. The standards are as follows:

[0140] Advantages: It can lift and slowly peel off the complete membrane structure from the skin surface;

[0141] Good: When more than 50% of the membrane is peeled off from the skin surface, the membrane structure is intact, but the membrane structure is destroyed when further peeled off, and it is not an intact membrane structure;

[0142] Poor: Cannot be lifted, or although it can be lifted, less than 50% of the membrane structure is peeled off.

[0143] II. Transdermal water loss test

[0144] Apply the ointment directly to clean skin, spreading it evenly, three times daily. Before product use, and after 2, 5, and 10 days of use, collect transepidermal water loss data using a Tewameter. Measurements are based on the diffusion law, as shown in the following formula:

[0145] ;

[0146] Where: A - surface area (m²) 2 M - moisture loss (g); T - time (h); D - diffusion constant (±0.0877 g / m•h•mm Hg); p - atmospheric vapor pressure (mm Hg); x - distance from skin surface to measurement point (m).

[0147] Diffusion flow rate dm / dt represents the amount of water transported per centimeter over a period of time. 2The density gradient is proportional to the area A and the concentration change per unit distance dp / dx. This law is only valid within a uniform diffusion region 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, along with the measurement electronics and calibration data, are located inside the probe. The probe's measuring head is a narrow hollow cylinder (10 mm in diameter and 20 mm in height) to minimize the effects of air turbulence inside the probe.

[0148] III. Mechanical Property Testing

[0149] To more accurately compare the film strength formed by different products, the following simulation test was conducted: Each formulation was applied to the surface of an object to prepare a film structure with dimensions of 50mm × 4mm × 3mm. Tensile strength was tested using a Shimadzu AGS-X tester at a speed of 10cm / minute. Three samples were tested for each product, and the average value was taken as the final result.

[0150] IV. Test Results

[0151] The test results are shown in Table 1.

[0152] Table 1

[0153]

[0154] Although the 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 adjustments or changes may be made to the exemplary embodiments described in this specification without departing from the scope or spirit of the invention. The scope of the claims should be interpreted in the broadest possible sense to cover all modifications and equivalent structures and functions.

Claims

1. A medical sodium hyaluronate ointment, characterized by, It is composed of the following raw materials: 1% cross-linked polyacrylic acid, 5% glycerol, 1% oligomeric sodium hyaluronate, 0.2% carboxymethyl cellulose, 0.5% triethanolamine, 0.2% phenoxyethanol, 0.1% vitamin B3, the balance is water; wherein the molecular weight of the oligomeric sodium hyaluronate is 6348 Da, and the molecular weight of the cross-linked polyacrylic acid is 20KDa.

2. A medical device, characterized by A container comprising the medical sodium hyaluronate ointment according to claim 1.

3. The medical device of claim 2, wherein, The container comprises a syringe assembly, an ointment tube or a plastic bottle.

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