Hyaluronic acid dressing and its application in the treatment of dermatitis

Abstract

The present application provides a hyaluronic acid dressing, which is prepared by the following method: (1) Prepare aqueous solution 1 containing 2-5% w / v hyaluronic acid and 1-3% w / v calcium chloride; (2) Prepare aqueous solution 2 containing 1-5% w / v plant polysaccharide and 1-3% w / v aldehyde-polyethylene glycol-aldehyde; (3) Mix aqueous solution 1 and aqueous solution 2 and add them to a mold; (4) Demold after waiting for 20-60 minutes to obtain a double-network hydrogel; (5) Adhere the double-network hydrogel to a substrate to obtain the hyaluronic acid dressing. The present application constructs a double-network gel by selecting a suitable and feasible plant polysaccharide together with hyaluronic acid. While providing good mechanical properties, the plant polysaccharide also provides good anti-inflammatory, anti-irritant, and antioxidant effects.

Description

Technical Field

[0001] This application belongs to the fields of skin dressings and the treatment of skin diseases. Specifically, this application provides a hyaluronic acid dressing and its application in the treatment of dermatitis. Background Art

[0002] Dermatitis may be caused by factors such as external stimuli and autoimmune reactions, and is a common skin disease. For most dermatitis cases, using topical medications to provide suitable humidity and to provide soothing, antioxidant and other effects is a common treatment method.

[0003] Hydrogels are polymers cross-linked by natural or artificial polysaccharides. They have a three-dimensional network structure, can accommodate a large amount of water and drugs, and can provide antioxidant, anti-inflammatory and other effects while having a moisturizing effect. Using hydrogels prepared from raw materials such as hyaluronic acid and chitosan to treat dermatitis is a common choice in clinical practice. Summary of the Invention

[0004] To further improve the effect of the hyaluronic acid dressing and balance factors such as the reported effects, molecular weight, and price, the applicant selected to introduce astragalus polysaccharide, scutellaria polysaccharide, honeysuckle polysaccharide, and porphyra yezoensis polysaccharide into the hyaluronic acid hydrogel, and used calcium chloride and aldehyde-polyethylene glycol-aldehyde to form a double-network hydrogel to balance the relationship between gel strength and effect.

[0005] On the one hand, this application provides a hyaluronic acid dressing, which is prepared by the following method:

[0006] (1) Prepare aqueous solution 1 containing 2-5% w / v hyaluronic acid and 1-3% w / v calcium chloride;

[0007] (2) Prepare aqueous solution 2 containing 1-5% w / v plant polysaccharide and 1-3% w / v aldehyde-polyethylene glycol-aldehyde;

[0008] (3) Mix aqueous solution 1 and aqueous solution 2, and add them to a mold;

[0009] (4) Demold after waiting for 20-60 minutes to obtain a double-network hydrogel;

[0010] (5) Adhere the double-network hydrogel to a substrate to obtain a hyaluronic acid dressing.

[0011] Further, the plant polysaccharide is scutellaria polysaccharide or porphyra yezoensis polysaccharide.

[0012] Further, the plant polysaccharide is scutellaria polysaccharide.

[0013] Further, the hyaluronic acid dressing is prepared by the following method:

[0014] (1) Prepare aqueous solution 1 containing 2.5 - 3.5% w / v hyaluronic acid and 1.5 - 2% w / v calcium chloride;

[0015] (2) Prepare aqueous solution 2 containing 2 - 2.5% w / v plant polysaccharide and 2 - 2.5% w / v aldehyde - polyethylene glycol - aldehyde;

[0016] (3) Mix aqueous solution 1 and aqueous solution 2 in equal volume and add them to a mold;

[0017] (4) Demold after waiting for 20 - 60 minutes to obtain a double - network hydrogel;

[0018] (5) Adhere the double - network hydrogel to a substrate to obtain a hyaluronic acid dressing.

[0019] Further, in step (4), demold after waiting for 20 - 60 minutes at 20 - 30 °C to obtain a double - network hydrogel.

[0020] Further, the hyaluronic acid dressing is prepared by the following method:

[0021] (1) Prepare aqueous solution 1 containing 3% w / v hyaluronic acid and 1.5% w / v calcium chloride;

[0022] (2) Prepare aqueous solution 2 containing 2% w / v plant polysaccharide and 2% w / v aldehyde - polyethylene glycol - aldehyde;

[0023] (3) Mix aqueous solution 1 and aqueous solution 2 in equal volume and add them to a mold;

[0024] (4) Demold after waiting for 30 minutes at 20 - 30 °C to obtain a double - network hydrogel;

[0025] (5) Adhere the double - network hydrogel to a substrate to obtain a hyaluronic acid dressing.

[0026] The adhesion process in step (5) can be carried out by various known methods in the art, including but not limited to adding a sticky adhesion layer between the substrate and the double - network hydrogel, placing the substrate at the bottom of the mold, and infiltrating the substrate layer during gel formation.

[0027] Further, the substrate is non - woven fabric.

[0028] Further, the preparation method of the hyaluronic acid dressing further includes a cutting and / or sterilization step.

[0029] On the other hand, the present application provides the use of the above - mentioned hyaluronic acid dressing in the preparation of a drug for treating dermatitis.

[0030] Further, the drug is a gel patch.

[0031] In addition to the hyaluronic acid dressing of the present application, the gel patch may also contain other active ingredients such as hormones and Chinese medicine extracts.

[0032] In addition to the hyaluronic acid dressing of the present application, the gel patch may also include components or structures such as water-impermeable packaging to keep the product moist, adhesive parts to assist in fixation, other matrix layers to maintain the mechanical strength of the product, antioxidants, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is the DPPH free radical scavenging rate result.

[0034] Figure 2 This is the result of anti-irritation performance test.

[0035] Figure 3 Test results for anti-inflammatory properties. DETAILED DESCRIPTION

[0036] Example 1 Main reagents and instruments

[0037] Hyaluronic acid (molecular weight 8-1.2×10 6 ): Made by the applicant.

[0038] Refined Astragalus polysaccharide (>95%), refined Scutellaria baicalensis polysaccharide (>95%), refined Honeysuckle polysaccharide (>95%); Leshengyuan Biotechnology (Nanjing) Co., Ltd.

[0039] Refined Porphyra yezoensis polysaccharide (>95%): Lanzhou Waterless Biotechnology Co., Ltd.

[0040] Aldehyde-polyethylene glycol-aldehyde (also known as dialdehyde polyethylene glycol): Chongqing Yusi Pharmaceutical Technology Co., Ltd.

[0041] Other reagents such as calcium chloride were all domestically produced.

[0042] Skin detector: MC2600 from ISEMAC.

[0043] Texture analyzer: Baosheng TA.XTC-20.

[0044] Example 2 Gel performance detection method

[0045] Free radical scavenging effect detection:

[0046] Take 30 mg of the newly prepared gel sample, mix it with 5 mL of 0.1 mM DPPH anhydrous ethanol solution, and react at 25 ° C in the dark for 30 min; use a spectrophotometer to measure the absorbance of the sample reaction solution, the control reaction solution (5 mL of anhydrous ethanol + 30 mg of sample) and the reference solution (5 mL of anhydrous ethanol + 5 mL of 0.1 mM DPPH anhydrous ethanol solution) at 517 nm.

[0047] DPPH radical scavenging rate % = (A control - A sample) / (A control - A reference) × 100%, and the average value is taken from three parallel experiments.

[0048] Detection of anti - irritation effect:

[0049] Fix male SD rats, remove the back hair, and demarcate a 1.5 cm × 1.5 cm test area on the flat areas on both the left and right sides of the spine (with a spacing of more than 2 cm, and at most 4 areas can be demarcated for each SD rat).

[0050] After washing with pure water, use a skin detector to detect the red value of the skin in the area; apply 30 μl of 50% w / v capsaicin aqueous solution; wait for 20 minutes; attach a gel approximately the size of the detection area to the detection area (apply pure water as a control and fix with adhesive tape and non - woven fabric if necessary); detect the red value again after 30 minutes.

[0051] Inhibition rate of red value change % = (control red value - gel red value) / (control red value - initial red value) × 100%, and the average value is taken from 5 SD rats.

[0052] Detection of anti - inflammatory effect:

[0053] Fix male SD rats and measure the thickness of both plantar surfaces.

[0054] Apply 50 μL of physiological saline containing 2% carrageenan to both plantar surfaces, wash after 60 minutes; attach a gel approximately the size of the detection area to the right hind plantar surface, and do not treat the left hind plantar surface after washing; measure the plantar thickness again after 120 minutes after washing.

[0055] Edema inhibition rate % = (1 - (right thickness - right initial thickness) / (left thickness - left initial thickness)) × 100%, and the average value is taken from 5 SD rats.

[0056] Test the maximum stress and maximum strain

[0057] Use a gel strip of 3 cm × 1 cm × 0.5 cm to test the maximum stress and maximum strain on the above - mentioned texture analyzer.

[0058] Example 3 Basic preparation method of the gel

[0059] Single - network hydrogel:

[0060] Prepare an aqueous solution containing 3% w / v hyaluronic acid and 1.5% w / v calcium chloride, add it to a mold, and demold after 30 minutes at room temperature to obtain a single - network hydrogel.

[0061] An aqueous solution containing 3% w / v hyaluronic acid, 2% w / v calcium chloride, and 2% w / v astragalus polysaccharide / scutellaria baicalensis polysaccharide / honeysuckle polysaccharide / porphyra yezoensis polysaccharide was prepared and added into a mold. The mold was demolded after 30 minutes at room temperature to obtain a single network hydrogel loaded with plant polysaccharides.

[0062] Double network hydrogel:

[0063] Prepare aqueous solution 1 containing 3% w / v hyaluronic acid and 1.5% w / v calcium chloride; prepare aqueous solution 2 containing 2% w / v astragalus polysaccharide / scutellaria polysaccharide / honeysuckle polysaccharide / porphyra yezoensis polysaccharide and 2% w / v aldehyde-polyethylene glycol-aldehyde; mix aqueous solution 1 and aqueous solution 2 in equal volumes, add into a mold, and demold after 30 minutes at room temperature to obtain a double network hydrogel.

[0064] Example 4 Mechanical properties of gel

[0065] Mechanical properties have a very significant impact on the convenience and effectiveness of dressing use. Better mechanical properties can ensure the stability of the dressing during movement and bending.

[0066] According to the method in Example 3, the applicant prepared a single network hydrogel containing only hyaluronic acid and a single network hydrogel loaded with plant polysaccharides, and tested their mechanical properties. The results are shown in Table 1:

[0067] Table 1 Mechanical properties of single network hydrogels

[0068]

[0069] The results showed that except for the polysaccharide of Porphyra yezoensis (high agar content) with good gelling performance, the addition of other polysaccharides had an adverse effect on the mechanical properties of the gel, which should be related to the large number of small fragments in the polysaccharides of Astragalus, Scutellaria baicalensis, and Honeysuckle and their sugar chain characteristics.

[0070] The applicant further tried to use calcium chloride and aldehyde-polyethylene glycol-aldehyde to construct a double network gel to improve the mechanical properties (according to the method of Example 3). The results are shown in Table 2

[0071] Table 2 Mechanical properties of double network hydrogels

[0072]

[0073] The results showed that, except for honeysuckle polysaccharide, the mechanical properties of double network gels with the addition of other plant polysaccharides were improved, among which the improvements in the Scutellaria baicalensis and Porphyra yezoensis polysaccharide groups were more obvious.

[0074] Example 5 Biological properties of gel

[0075] The antioxidant, anti-irritant and anti-inflammatory properties of 1, 1-1, 2, 2-1, 3, 3-1, 5, 5-1 were tested.

[0076] The results of DPPH radical scavenging rate are as Figure 1 shown. The results show that adding more plant polysaccharides helps to improve the radical scavenging rate of the gel. However, after forming the double-network gel, the effect of Astragalus polysaccharide, which had the best effect in the single-network gel, decreased instead (related to the sugar chain conformation and the exposure of side chains / groups). After forming the double-network gel, the DPPH radical scavenging effect of Scutellaria polysaccharide was significantly improved.

[0077] The results of anti-irritant property test are as Figure 2 shown. The results are similar to those of the DPPH radical scavenging rate. After forming the double-network gel, the effect of Astragalus polysaccharide, which had the best effect in the single-network gel, decreased instead, while the anti-irritant effect of Scutellaria polysaccharide was significantly improved.

[0078] The results of anti-inflammatory property test are as Figure 3 shown. The results show that for both single-network hydrogels and double-network hydrogels, there was no significant change in the effects of the gels without polysaccharides and hyaluronic acid and the hyaluronic acid gels containing Astragalus polysaccharide. For the hyaluronic acid gels containing Scutellaria polysaccharide and Porphyra yezoensis polysaccharide, the anti-inflammatory property was enhanced after forming the double-network hydrogel.

Claims

1. A hyaluronic acid dressing, characterized in that, The hyaluronic acid dressing is prepared by the following method: (1) Prepare aqueous solution 1 containing 2.5 - 3.5% w / v hyaluronic acid and 1.5 - 2% w / v calcium chloride; (2) Prepare aqueous solution 2 containing 2 - 2.5% w / v scutellaria polysaccharide and 2 - 2.5% w / v aldehyde - polyethylene glycol - aldehyde; (3) Mix aqueous solution 1 and aqueous solution 2 in equal volumes and add them to a mold; (4) Demold after waiting for 20 - 60 minutes to obtain a double - network hydrogel; (5) Adhere the double - network hydrogel to a substrate to obtain the hyaluronic acid dressing.

2. The hyaluronic acid dressing according to claim 1, wherein in step (4), demold after waiting for 20 - 60 minutes at 20 - 30 °C to obtain a double - network hydrogel.

3. The hyaluronic acid dressing according to claim 1, which is prepared by the following method: (1) Prepare aqueous solution 1 containing 3% w / v hyaluronic acid and 1.5% w / v calcium chloride; (2) Prepare aqueous solution 2 containing 2% w / v scutellaria polysaccharide and 2% w / v aldehyde - polyethylene glycol - aldehyde; (3) Mix aqueous solution 1 and aqueous solution 2 in equal volumes and add them to a mold; (4) Demold after waiting for 30 minutes at 20 - 30 °C to obtain a double - network hydrogel; (5) Adhere the double - network hydrogel to a substrate to obtain the hyaluronic acid dressing.

4. The hyaluronic acid dressing according to claim 1, wherein the substrate is non - woven fabric.

5. The preparation method of the hyaluronic acid dressing according to claim 1 further includes a cutting and / or sterilization step.

6. Use of the hyaluronic acid dressing according to any one of claims 1 - 5 in the preparation of a drug for treating dermatitis.

7. The use according to claim 6, wherein the drug is a hydrogel patch.

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