CN118697924A - Composition containing hyaluronic acid and sterile hyaluronic acid dressing and application thereof - Google Patents

Abstract

The invention relates to the technical field of biological medicines, and particularly provides a composition containing hyaluronic acid, a sterile hyaluronic acid dressing patch and application. The hyaluronic acid-containing composition of the present invention comprises, in parts by mass: 10-40 parts of hyaluronic acid, 2-15 parts of angelica lactone, 2-15 parts of lycium barbarum polysaccharide and 1-10 parts of nicotinamide. Compared with the prior art, the hyaluronic acid-containing composition and the sterile hyaluronic acid dressing patch can promote regeneration and repair of damaged tissues and prevent scars.

Description

Composition containing hyaluronic acid and sterile hyaluronic acid dressing and application thereof

Technical Field

The present invention relates to the field of biomedical technology, and more specifically to a composition containing hyaluronic acid and a sterile hyaluronic acid dressing and application thereof.

Background Art

The skin is the first line of defense against the external environment. The stratum corneum is the outermost layer of the skin, which is composed of dense dead cells without nuclei, forming a hydrophobic surface as the main barrier. For the penetration of the stratum corneum, hydrophobic molecules have obvious advantages over hydrophilic molecules. Skin hydration is essential for enhancing skin permeability. When the stratum corneum is exposed to water, the tissue will swell and form a channel for the transport of molecules into the skin. With the improvement of living standards, people have a higher pursuit of quality of life. In recent years, the laser beauty industry has developed rapidly. Fractional laser and intense pulsed light have become routine technologies in laser cosmetology and dermatology, and are widely welcomed for the treatment of skin pigmentation diseases, depressed or hypertrophic scars, photoaging, etc. Since the basic principle of laser treatment is based on thermal effect and photochemical effect, there will inevitably be a certain degree of damage to skin tissue and structure after surgery, including local skin erythema, slight edema, scab and pain.

Scars are caused by the damage to the skin caused by the above-mentioned trauma or disease. When the normal healing process of the wound is interrupted, abnormal scars will form. Human skin mainly consists of three layers: epidermis, dermis and subcutaneous tissue. Generally speaking, as long as the dermis is injured, scars may be left. At present, the main methods of improving or treating scars include gene therapy, intra-scar drug injection, oral anti-scar drugs, cryotherapy, pressure therapy, laser therapy, silicone gel film products, radiotherapy, etc., and the therapeutic effects of various treatment methods are also different. However, there is a problem of a single mechanism of action. Some have poor permeability and are difficult to penetrate the stratum corneum and cannot enter the dermis, resulting in poor anti-inflammatory effects. Some cannot prevent the volatilization of moisture on the surface of the scar, resulting in slow repair. Some cannot isolate harmful microorganisms in the external environment, resulting in secondary infection.

Currently, there are no products containing hyaluronic acid that have a good recovery effect on scars.

Summary of the invention

In view of this, the purpose of the present invention is to provide a composition containing hyaluronic acid and a sterile hyaluronic acid dressing patch and application. The composition containing hyaluronic acid of the present invention can promote the regeneration and repair of damaged tissues and prevent the formation of scars.

In order to achieve the above object, the present invention adopts the following technical solutions:

The hyaluronic acid-containing composition comprises, by weight, 10 to 40 parts of hyaluronic acid, 2 to 15 parts of angelica lactone, 2 to 15 parts of wolfberry polysaccharides, and 1 to 10 parts of niacinamide.

Hyaluronic acid (HA) is a natural polysaccharide that is widely present in human tissues, especially in the skin, eyes and joint fluid. It is a very important bioactive molecule with multiple physiological functions and application values. The main functions include: moisturizing function: HA can absorb and retain water to maintain the moisture and elasticity of the skin; antioxidant function: HA can remove free radicals and protect skin cells from oxidative damage; anti-aging function: HA can reduce the symptoms of skin aging, such as wrinkles, sagging skin, etc.; anti-inflammatory function: HA can reduce the inflammatory response of the skin, relieve skin redness, swelling and pain; whitening function: HA can inhibit the production of melanin and maintain the whiteness and uniformity of the skin. In view of the above-mentioned multiple physiological functions, hyaluronic acid is widely used in the field of skin care products and medical supplies. In addition, in open burn wounds, topical HA can accelerate the healing of burn wounds and reduce scar formation. In the process of skin wound healing, the water absorption of long-chain HA establishes a moist environment suitable for wound repair for the wound and surrounding tissues, inhibits the migration of neutrophils, and reduces the inflammatory response.

Angelica lactone is a bioactive ingredient extracted from the Chinese herbal medicine Angelica sinensis. Angelica sinensis is a traditional Chinese herbal medicine with multiple functions such as nourishing blood and promoting blood circulation, regulating menstruation and relieving pain, nourishing the heart and calming the mind. Angelica lactone has antioxidant and anti-inflammatory effects, and can protect skin cells from oxidative damage and inflammatory reactions.

Lycium chinense polysaccharides are a kind of bioactive polysaccharide extracted from wolfberry. Lycium chinense has many functions such as nourishing yin and kidney, nourishing liver and improving eyesight, anti-aging, etc. Lycium chinense polysaccharides are mainly composed of 6 monosaccharide components: arabinose, glucose, galactose, mannose, xylose and rhamnose.

Nicotinamide, also known as nicotinamide, is a water-soluble vitamin belonging to the vitamin B family. Nicotinamide can improve the color and texture of the skin, reduce dullness and fatigue of the skin; nicotinamide can also enhance the barrier function of the skin and reduce skin damage and infection.

Preferably, the hyaluronic acid-containing composition comprises, by weight: 10 to 20 parts of hyaluronic acid, 4 to 7 parts of angelica lactone, 3 to 9 parts of wolfberry polysaccharides, and 1 to 4 parts of niacinamide.

Preferably, the hyaluronic acid is hyaluronic acid or a derivative thereof.

Preferably, the hyaluronic acid derivative includes hyaluronate; the hyaluronate includes sodium hyaluronate, potassium hyaluronate or zinc hyaluronate; the molecular weight of the sodium hyaluronate is 1 million to 1.5 million.

Preferably, the angelica lactone comprises Alpha-angelica lactone.

The hyaluronic acid-containing composition comprises, by weight: 15 parts of sodium hyaluronate, 6 parts of angelica lactone, 5 parts of wolfberry polysaccharides, and 3 parts of niacinamide.

Preferably, the hyaluronic acid-containing composition comprises, by mass, 20 parts of sodium hyaluronate, 4 parts of angelica lactone, 3 parts of wolfberry polysaccharides, and 1 part of niacinamide.

Preferably, the hyaluronic acid-containing composition comprises, by mass, 10 parts of sodium hyaluronate, 7 parts of angelica lactone, 9 parts of wolfberry polysaccharides, and 4 parts of niacinamide.

The present invention also provides application of the composition containing hyaluronic acid in promoting cell proliferation.

Preferably, the concentration of the composition containing hyaluronic acid is 50-100 μg/mL.

Preferably, the cells include human skin fibroblasts. Fibroblasts are the main connective tissue cells present in various tissues of the human body and have important biological functions, including synthesis of collagen, extracellular matrix, etc.

The present invention also provides a sterile hyaluronic acid dressing patch, which is composed of a membrane cloth and a dressing liquid arranged on the membrane cloth;

The dressing liquid comprises the hyaluronic acid-containing composition and acceptable auxiliary materials.

Preferably, in the dressing solution, the concentration of the composition containing hyaluronic acid is 10 to 22 wt %.

Preferably, the auxiliary materials include one or more of solvents, humectants, thickeners and preservatives.

Preferably, the solvent includes water and/or 1,2-pentanediol; the humectant includes glycerol; the thickener includes carbomer; and the preservative includes glyceryl caprylate.

Preferably, the method for preparing the dressing liquid comprises: adding the above raw materials into an emulsifying pot and stirring at 2000 rpm for 3 hours.

Preferably, the membrane fabric comprises non-woven fabric.

Preferably, the preparation method of the sterile hyaluronic acid dressing patch comprises: sterilizing the dressing liquid through a filtering device (0.5 μm); and fully soaking the dressing liquid in a non-woven fabric in a sterile environment to obtain a sterile hyaluronic acid dressing patch.

The sterile hyaluronic acid dressing of the present invention can be cut into any size for use according to actual needs.

The present invention also provides application of the sterile hyaluronic acid dressing in preparing scar repair products.

Preferably, in the dressing solution, the concentration of the composition containing hyaluronic acid is 10 to 22 wt %.

Compared with the prior art, the present invention has the following beneficial effects:

1. The hyaluronic acid-containing composition and the sterile hyaluronic acid dressing of the present invention can promote the regeneration and repair of damaged tissues and prevent the formation of scars.

2. The hyaluronic acid-containing composition and the sterile hyaluronic acid dressing of the present invention have low risks and can be used as products for repairing scars.

3. The composition containing hyaluronic acid of the present invention has multifunctionality: in addition to promoting scar repair, the composition containing hyaluronic acid can also promote cell proliferation.

DETAILED DESCRIPTION

The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

To further illustrate the present invention, the following examples are used to provide a detailed description. The raw materials used in the following examples and comparative examples of the present invention are all commercially available products; the molecular weight of sodium hyaluronate is 1 million to 1.5 million; angelica lactone is Alpha-angelica lactone; the sodium hyaluronate, angelica lactone, Lycium barbarum polysaccharide and niacinamide used in the examples and comparative examples are all purchased from Shanghai Yuanye Biotechnology Co., Ltd.

Example 1

The hyaluronic acid-containing composition of this embodiment is composed of the following components:

Sodium hyaluronate 15g, angelica lactone 6g, wolfberry polysaccharide 5g, niacinamide 3g.

Example 2

The hyaluronic acid-containing composition of this embodiment is composed of the following components:

Sodium hyaluronate 20g, angelica lactone 4g, wolfberry polysaccharide 3g, niacinamide 1g.

Example 3

The hyaluronic acid-containing composition of this embodiment is composed of the following components:

Sodium hyaluronate 10g, angelica lactone 7g, wolfberry polysaccharide 9g, niacinamide 4g.

Application Example 1

The hyaluronic acid-containing composition obtained in Example 1 is made into a dressing liquid, and the formula of the dressing liquid consists of the following components: a composition containing hyaluronic acid: 16wt%; 1,2-pentanediol: 2wt%; carbomer: 1.0wt%; glyceryl caprylate: 0.8wt%; the remainder is water; the preparation method comprises: adding the above raw materials to an emulsifying pot, stirring at 2000 rpm for 3 hours to mix them evenly.

The preparation method of the sterile hyaluronic acid dressing patch comprises: sterilizing the dressing liquid through a filtering device (0.5 μm); and fully soaking 25 g of the dressing liquid in a non-woven fabric in a sterile environment to obtain the sterile hyaluronic acid dressing patch.

Application Example 2

The hyaluronic acid-containing composition obtained in Example 1 was made into a dressing solution, and the formula consisted of the following components: hyaluronic acid-containing composition: 14wt%; 1,2-pentanediol: 2wt%; carbomer: 1.0wt%; glyceryl caprylate: 0.8wt%; and the balance was water.

The preparation method of the dressing liquid and the sterile hyaluronic acid dressing patch of this application example is carried out by referring to the steps in Application Example 1.

Application Example 3

The hyaluronic acid-containing composition obtained in Example 1 was made into a dressing solution, and the formula consisted of the following components: hyaluronic acid-containing composition: 10wt%; 1,2-pentanediol: 1wt%; carbomer: 1.0wt%; glyceryl caprylate: 0.8wt%; and the balance was water.

The preparation method of the dressing liquid and the sterile hyaluronic acid dressing patch of this application example is carried out by referring to the steps in Application Example 1.

Application Example 4

The hyaluronic acid-containing composition obtained in Example 1 was made into a dressing solution, and the formula consisted of the following components: 28wt% of the hyaluronic acid-containing composition; 1wt% of 1,2-pentanediol; 0.7wt% of carbomer; 0.8wt% of glyceryl caprylate; and the balance was water.

The preparation method of the dressing liquid and the sterile hyaluronic acid dressing patch of this application example is carried out by referring to the steps in Application Example 1.

Comparative Example 1

The composition of this comparative example is different from that of Example 1 in that this comparative example only includes sodium hyaluronate, angelica lactone and wolfberry polysaccharide, and the missing amount of niacinamide is distributed to the corresponding components according to the ratio of the other three substances.

Comparative Example 2

The composition of this comparative example is different from that of Example 1 in that this comparative example only includes sodium hyaluronate, angelica lactone and niacinamide, and the missing amount of Lycium barbarum polysaccharide is distributed to the corresponding components according to the ratio of the other three substances.

Comparative Example 3

The composition of this comparative example is different from that of Example 1 in that this comparative example only includes sodium hyaluronate, Lycium barbarum polysaccharide and niacinamide, and the missing amount of angelica lactone is distributed to the corresponding components according to the ratio of the other three substances.

Comparative Example 4

The composition of this comparative example is different from that of Example 1 in that this comparative example only includes angelica lactone, Lycium barbarum polysaccharide and niacinamide, and the missing amount of sodium hyaluronate is distributed to the corresponding components according to the ratio of the other three substances.

Comparative Example 5

The composition of this comparative example is different from that of Example 1 in that wolfberry polysaccharide is replaced with glucose in this comparative example; the other components and contents remain unchanged.

Test Example 1

This test example uses the MTT method to explore the proliferation promoting effect of the composition obtained in the embodiment and the comparative example on human skin fibroblasts (HSF), which specifically includes the following steps:

Human skin fibroblasts in the logarithmic growth phase were taken, digested, and a cell suspension of 1×10 ⁵ /mL was prepared with a DMEM medium containing 10% fetal bovine serum and 1% double antibody, inoculated in a 96-well plate, 100 μL per well, and cultured in a 37°C, 5% CO ₂ incubator for 24 hours. The culture medium was adjusted to contain an experimental group, a negative control group (containing an equal amount of cell suspension) and a blank control group (containing an equal amount of 1% double antibody DMEM culture fluid). The experimental group was added with the composition of the embodiment and the comparative example (concentration of 50-150 μg/mL), and each well was added with 1% double antibody DMEM culture medium to continue culture. After 24 hours of culture, the culture medium was discarded, 20 μL MTT solution (5 mg/mL)/well was added, and the cells were cultured in an incubator for 4 hours, the supernatant was discarded, 100 μL DMSO was added to each well, and the cells were shaken on a shaker for 10 minutes. The absorbance of each well was measured at 490 nm using an enzyme marker. At the same time, an experiment of a blank group without a sample solution was performed, and the proliferation survival rate was calculated. The experimental results are shown in Table 1.

Proliferation survival rate (%) = (absorbance value of experimental group - absorbance value of blank group) / (absorbance value of negative control group - absorbance value of blank group) × 100%

Table 1

Group concentration Proliferation survival rate (%) Negative control group / 100 Example 1 50 μg/mL 264.1 Example 1 100 μg/mL 270.6 Example 1 150 μg/mL 243.7 Example 2 100 μg/mL 260.5 Example 3 100 μg/mL 263.6 Comparative Example 1 100 μg/mL 212.8 Comparative Example 2 100 μg/mL 204.3 Comparative Example 3 100 μg/mL 206.3 Comparative Example 4 100 μg/mL 215.1 Comparative Example 5 100 μg/mL 213.8

It can be seen from Table 1 that, compared with the comparative example, the composition containing hyaluronic acid prepared in the embodiment of the present invention has a significant promoting effect on the proliferation of human skin fibroblasts, among which the composition containing hyaluronic acid at a concentration of 100 μg/mL has the best promoting effect on the proliferation of human skin fibroblasts.

Test Example 2

This test example explores the basic properties of the sterile hyaluronic acid dressing obtained in the application example, including the following contents:

1. Appearance

Take 5 tablets of this product and inspect visually to see if they meet the requirements of 2.1.

2. Basic size

Take 5 tablets of this product and measure them using general or special measuring tools in accordance with the requirements of 2.2.

3. Loading quantity

Take 5 tablets of this product and determine them by weight according to General Chapter 0942 Minimum Fill Inspection Method of the "Chinese Pharmacopoeia" (Volume 4 of the 2020 Edition), which complies with the provisions under 2.3.

4. pH value

Take about 20 ml of the squeezed liquid of this product and determine it according to the general chapter 0631 pH determination method of the "Chinese Pharmacopoeia" (Volume 4 of the 2020 edition), which complies with the requirements of 2.4.

5. Heavy Metals

Take 1.0g of the squeezed liquid of this product and determine it according to the second method of heavy metal inspection method in General Chapter 0821 of the "Chinese Pharmacopoeia" (Volume 4 of the 2020 edition), which complies with the requirements of 2.5.

6. Viscosity

Take 5 tablets of the extruded liquid and measure its viscosity at 25°C according to the viscosity determination method (Method 3 of 0633 of Part IV of the Chinese Pharmacopoeia (2020 Edition)), which meets the requirements of 2.7.

7. Film-forming property

Take an appropriate amount of this product and spread it evenly on the culture dish. Place it in a 37℃ forced air drying oven to dry it. Then conduct a visual inspection with corrected vision under natural light. The result shall comply with the requirements of 2.7.

8. Identification

The determination was carried out according to the identification method specified in 5.3 of YY/T 0308-2015, and the results met the requirements of 2.8.

9. Sodium hyaluronate content

According to the method in Appendix A of YY/T 0308-2015, the content of sodium hyaluronate is in the range of 5.0-11.0 mg/ml, which meets the requirements of 2.9.

10. Biological performance

Take an appropriate amount of this product and measure it according to Part IV of the 2020 edition of the Chinese Pharmacopoeia (General Chapter 1101 Sterility Test Method Direct Inoculation Method), which complies with the provisions under Item 2.9.

Test Example 3

This test example explores the repair effect of the sterile hyaluronic acid dressing obtained in the application example on scars in rats, and specifically includes the following steps:

30 male SD rats aged 7-8 weeks were selected, anesthetized, and the back hair was shaved. A wound with a diameter of 1 cm was cut on the back of the mice with sterilized scissors. The rats were randomly divided into 6 groups, group 1 (the scar gel prepared in Example 1 was applied to the wound), group 2 (the scar gel prepared in Example 2 was applied to the wound), group 3 (the scar gel prepared in Example 3 was applied to the wound), group 4 (the scar gel prepared in Example 4 was applied to the wound), and a control group (the wound was disinfected with iodine). Apply once in the morning and evening every day, each time for 10 minutes.

The wound healing and scar formation were observed at 3d, 6d, 9d and 12d respectively. Wound healing rate (%) = (wound area on day 0 - wound area on day n) / wound area on day 0 × 100%; the experimental results are shown in Tables 2 and 3.

Table 2 Wound healing rate of rats (%)

Table 3 Wound scar formation in rats

Group Scar formation 1 group There is no proliferation at the wound site and no scars are produced 2 groups There is no proliferation at the wound site and no scars are produced 3 groups There is no proliferation at the wound site and no scars are produced 4 groups Slight scarring at the wound site, no hyperplasia Control group Obvious scars and slight hyperplasia appear at the wound site

It can be seen from Table 2 and Table 3 that the dressing of the application example of the present invention has a significant effect of promoting the healing of the wounds of rats and can reduce the formation of scars.

The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims (10)

1. The hyaluronic acid-containing composition is characterized by comprising the following components in parts by mass: 10-40 parts of hyaluronic acid, 2-15 parts of angelica lactone, 2-15 parts of lycium barbarum polysaccharide and 1-10 parts of nicotinamide.

2. The hyaluronic acid-containing composition according to claim 1, characterized by comprising, in parts by mass: 10-20 parts of hyaluronic acid, 4-7 parts of angelica lactone, 3-9 parts of lycium barbarum polysaccharide and 1-4 parts of nicotinamide.

3. The hyaluronic acid-containing composition of claim 1, wherein the hyaluronic acid comprises hyaluronic acid or a derivative thereof.

4. The hyaluronic acid-containing composition according to claim 1, characterized by comprising, in parts by mass: 15 parts of sodium hyaluronate, 6 parts of angelica lactone, 5 parts of lycium barbarum polysaccharide and 3 parts of nicotinamide;

or the hyaluronic acid-containing composition comprises the following components in parts by mass: 20 parts of sodium hyaluronate, 4 parts of angelica lactone, 3 parts of lycium barbarum polysaccharide and 1 part of nicotinamide;

or the hyaluronic acid-containing composition comprises the following components in parts by mass: 10 parts of sodium hyaluronate, 7 parts of angelica lactone, 9 parts of lycium barbarum polysaccharide and 4 parts of nicotinamide.

5. Use of the hyaluronic acid-containing composition of any of claims 1-4 for promoting cell proliferation.

6. The use according to claim 5, wherein the concentration of the hyaluronic acid-containing composition is 50-100 μg/mL.

7. The sterile hyaluronic acid dressing patch is characterized by comprising a film cloth and dressing liquid arranged on the film cloth;

The dressing solution comprises the hyaluronic acid-containing composition of any of claims 1-4, and acceptable excipients.

8. The sterile hyaluronic acid dressing according to claim 7, wherein the concentration of the hyaluronic acid-containing composition in the dressing solution is 10-22 wt%.

9. The sterile hyaluronic acid dressing of claim 7, wherein the adjuvant comprises one or more of a solvent, a humectant, a thickener, a preservative.

10. Use of a sterile hyaluronic acid dressing patch according to any of claims 7-9 for the preparation of a scar repair product.