CN116139072A - Salvianolic acid A carbomer gel and application thereof - Google Patents

Abstract

The invention relates to the field of external medicines, and relates to a salvianolic acid A carbomer gel and application thereof. The salvianolic acid A carbomer gel is prepared from effective components of salvianolic acid A, vitamin C in matrix, ethanol, glycerol, carbomer 940, triethanolamine and deionized water according to a certain proportion. The salvianolic acid A carbomer gel prepared by the invention is light yellow, crystal clear, proper in viscosity and good in stability. Pharmacodynamics researches show that the salvianolic acid A carbomer gel has good treatment effect on the imiquimod-induced mice psoriasis-like disease model, has obvious advantages compared with other administration modes, and has no irritation to skin.

Description

A kind of salvianolic acid A carbomer gel and its application

Technical Field

The invention relates to the field of external medicines, and particularly relates to a salvianolic acid A carbomer gel and application thereof.

Background Art

Salvianolic acid A is a water-soluble phenolic acid compound contained in the dried roots and rhizomes of Salvia miltiorrhiza, a plant of the Labiatae family, and is one of the effective ingredients of Salvia miltiorrhiza. Studies in recent years have shown that SAA has significant activity in cardiovascular and cerebrovascular disease protection, liver damage resistance, diabetes and complications, anti-tumor, and anti-inflammatory aspects. Chinese patent CN202210128754.X discloses that salvianolic acid A is used as a drug to treat inflammatory diseases of the skin, especially psoriasis. Salvianolic acid A is a compound with strong antioxidant activity in nature, which is easily oxidized, unstable in aqueous solution, and more easily degraded during high-temperature sterilization. The current dosage forms of salvianolic acid A include injection preparations, tablets, capsules, oral liquid preparations, etc., and topical preparations have not yet been reported, and the use of topical preparations is an important requirement for the treatment of skin inflammatory diseases such as psoriasis. Therefore, developing salvianolic acid A into a topical preparation that can be used clinically for the treatment of skin inflammatory diseases is a difficult problem to be solved by medical researchers.

Carbomer 940 is a cross-linked polyacrylic acid polymer that can form a high-viscosity gel at a very low concentration. It has a variety of uses in medicines, and can be used as a thickener, suspending agent, gel matrix, bioadhesive material, and skeleton material for controlled-release agents. Carbomer has a simple process and good stability. It is often used in topical preparations and is widely used in lotions, creams, and gels.

This patent invents a tansolic acid A carbomer gel for the first time, and can effectively treat and improve psoriasis.

Summary of the invention

Purpose of the Invention

In order to overcome the above-mentioned defects of the prior art, the present invention provides a new dosage form of salvianolic acid A for targeted skin delivery - salvianolic acid A carbomer gel, including its preparation method and its pharmaceutical use. The production process of the invention is simple and controllable, with good stability, little skin irritation, little side effects and high safety.

Technical Solution

The invention provides a salvianolic acid A carbomer gel, comprising salvianolic acid A, carbomer 940, glycerol, triethanolamine, vitamin C and deionized water, wherein the components of the gel are prepared according to the following weight ratios: salvianolic acid A 0.001%-10%, carbomer 940 0.1%-3.0%, glycerol 20%, triethanolamine adjusted to pH 6-11, vitamin C 0.01%-1%, and the remainder is deionized water. The salvianolic acid A is a medicinal ingredient, carbomer 940 is a thickener, glycerol is a moisturizer, ethanol is a penetration enhancer, vitamin C is an antioxidant, and triethanolamine is a pH regulator.

After optimization, the components of the carbomer gel are prepared according to the following weight ratio: 0.05% to 0.1% of salvianolic acid A, 0.8% of carbomer 940, 20% of glycerol, triethanolamine adjusted to pH 6-7, 0.1% to 1% of vitamin C, and 78.1% to 79.05% of deionized water.

The skin diseases include psoriasis, contact dermatitis, diabetic dermatitis, allergic dermatitis, atopic dermatitis, stasis dermatitis, seborrheic dermatitis, eczema, urticaria, urticaria, acne, pimples, ultraviolet damage, sunburn, diabetic foot, trauma, and burns.

In particular, the salvianolic acid A carbomer gel can treat and improve the skin symptoms of psoriasis and has no irritation to damaged skin and no toxic side effects.

Beneficial effects:

The salvianolic acid A carbomer gel prepared by the present invention has good efficacy, good stability, no skin irritation, no side effects, a simple preparation method, high efficiency and low cost, and the prepared gel-like drug has a good therapeutic effect on psoriasis and shows more obvious advantages compared with intraperitoneal injection.

Description of the drawings:

Figure 1 is a graph showing the results of the linear relationship investigation of in vitro analysis of salvianolic acid A;

Figure 2 shows the results of in vitro antioxidant study of salvianolic acid A;

Figure 3 Appearance of salvianolic acid A carbomer gel;

FIG4 is a graph showing the results of an in vitro stability analysis of salvianolic acid A;

Figure 5 Salvianolic acid A carbomer gel effectively treats imiquimod-induced psoriasis in mice; A. Representative photos of skin lesions and H&E staining results; B. Body weight percentage; C. Clinical scores of skin tissue damage such as skin scaling, nodules, and erythema; D. Epidermal thickness;

Figure 6 Study on the irritation of salvianolic acid A carbomer gel; A. Representative photos of skin lesions and H&E staining results; B. Body weight percentage; C. Clinical scores of skin tissue damage such as skin scaling, nodules, and erythema; D. Epidermal thickness;

Figure 7 Transdermal delivery of imiquimod-induced psoriasis in mice is a more effective drug delivery method than intraperitoneal injection. A. Representative photos of skin lesions and H&E staining results. B. Body weight percentage. C. Clinical scores of skin tissue damage such as skin scaling, nodules, and erythema; D. Epidermal thickness;

Figure 8 Figure 8 Transdermal delivery of the preparation can effectively treat UVB-induced ultraviolet light damage model in mice; A. Representative photos of skin lesions and H&E staining results; B. Body weight percentage; C. Clinical scores of skin tissue damage such as skin scaling, nodules, and erythema; D. Epidermal thickness.

DETAILED DESCRIPTION

The present invention is described below through specific implementation methods.

Example 1: Analysis method of salvianolic acid A and construction of antioxidant scheme

1. Instruments and test drugs

Instrument: HPLC instrument Alliance2695, chromatography workstation, diode array detector, balance

Chromatographic column: _C18 column

Reagents: acetonitrile, chromatographic grade acetic acid, ultrapure water, vitamin C

Salvianolic acid A (Jiangxi Qingfeng Pharmaceutical Co., Ltd.)

2. Preparation of standard solution and test solution

(1) Preparation of standard solution: Prepare the standard solution of salvianolic acid A with 50% ethanol, 50 μl each, and dilute it in a gradient manner. Prepare it before use.

Standard concentration: 1mg/ml, 0.5mg/ml, 0.25mg/ml, 0.125mg/ml, 0.0625mg/ml, 0.03125mg/ml.

(2) Preparation of test solution: Accurately weigh 10 mg of salvianolic acid A sample and prepare a stock solution with a concentration of 10 mg/ml using 50% ethanol.

ml, use the above mother solution to prepare 1 ml of 2 mg/ml storage solution, a total of 4 tubes of storage solution, storage conditions are room temperature, room temperature +

1‰ vitamin C, 4℃, 4℃+1‰ vitamin C, all stored away from light.

3. Chromatographic conditions and system suitability test

Octadecylsilane bonded silica gel was used as filler; flow rate was 1.0 ml/min; detection wavelength was 286 nm; column temperature was 35°C; theoretical plate number was calculated based on the peak of salvianolic acid A and should not be less than 10,000. Sample volume was 10 μL; mobile phase was 0.1% acetic acid aqueous solution, acetonitrile. Elution was 25% acetonitrile for 12 minutes.

4. Investigation of linear relationship

Weigh the sample accurately and dilute it with double distilled water to form a series of standard solutions. Calculate the peak area according to the chromatographic conditions under "3. Chromatographic conditions and system suitability test", and draw the standard curve with the peak area integral value as the ordinate and the injection volume of each concentration reference substance as the abscissa. The results show that the sample solution has a good linear relationship in the following concentration range.

Table 1 Investigation of linear relationship of in vitro analysis of salvianolic acid A

5. Precision test

Take a 0.5 mg/ml sample solution and test it according to the chromatographic conditions under "3. Chromatographic conditions and system suitability test" and repeat the injection 5 times. The results show that the precision of this method is good.

Table 2 Precision of in vitro analysis of salvianolic acid A

concentration Peak area 1 Peak area 2 Peak area 3 Peak area 4 Peak area 5 RSD(%) 0.5mg/ml 192693 192285 192147 191866 191453 0.24

6. Stability test

According to the method of "2 (2) Preparation of test solution", the samples were tested at 0h, 24h, 36h, 48h and 60h respectively. The samples were diluted 4 times before being tested to a concentration of 0.5mg/ml and filtered with a 0.22μm filter membrane. The results showed that the samples were stable under the light-proof "4℃+VC" condition for 60h, while they were stable only for 36h under the "room temperature+VC" condition.

7. Repeatability Experiment

The results of three repeated loadings showed that the experimental conditions and results were reproducible.

Experimental results:

(1) In this experiment, HPLC analysis was successfully used to establish an in vitro analysis system for salvianolic acid A. As shown in Figures 1 and 2, the linear relationship investigation results showed a good linear relationship within the investigation range. Based on appropriate chromatographic conditions, the content changes of salvianolic acid A samples under different storage conditions over time were investigated.

(2) As shown in FIG3 , the results of the stability test show that the addition of 0.1% vitamin C can keep salvianolic acid A stable for 60 hours, and the storage effect at 4° C. away from light is better than that at room temperature, and it is almost not oxidized within 60 hours.

(3) Therefore, it is preferred that the preparation and storage process should be protected from light, and at least 0.1% vitamin C should be added to achieve the purpose of anti-oxidation. According to the implementation standard of external preparations, 1% vitamin C is used in the subsequent preparation process, and it has been verified that 1% vitamin C does not affect the efficacy of salvianolic acid A.

Example 2: Establishment of evaluation index determination method for salvianolic acid A carbomer gel and optimization of formulation process

Optimization of preparation method and investigation of physical properties of salvianolic acid A carbomer gel

1. Preparation method: A salvianolic acid A carbomer gel is prepared from the following raw materials in percentage by weight: 0.8% carbomer 940, 20% glycerol, triethanolamine adjusted to pH 6-7, 1% vitamin C, and deionized water to make up to 100 mL.

The preparation method of the salvianolic acid A carbomer gel of the present invention comprises the following steps:

(1) According to the weight percentage, add 30 ml of water and 20 ml of glycerol into a 500 ml beaker, and evenly sprinkle 0.8 g of Carbomer 940 resin under a magnetic stirrer; stir for about 4 hours to allow Carbomer 940 to fully swell, and let it stand overnight to eliminate bubbles.

(2) Dissolve 1 g of vitamin C in 10 ml of water according to weight percentage, add to the above (1) system, adjust the pH to about 6 with 50% triethanolamine, and add water to 100 ml to prepare a gel matrix.

(3) Dilute salvianolic acid A with water in advance to prepare mother solutions with concentrations of 0.05% and 0.1%, respectively, and mix them thoroughly with 100 ml of the matrix in (2), and store them in a sealed container away from light.

2. Establishment of evaluation index measurement method:

(1) Stability determination

Take a certain weight of gel matrix and conduct a thermal acceleration centrifugation experiment: centrifuge at 3000 rpm for 30 minutes to examine the changes in its physical and chemical properties.

Take a certain weight of gel matrix and conduct a heat resistance test: place it in a 55℃ water bath for 6 hours and observe the changes in its physical and chemical properties.

Take a certain weight of gel matrix and conduct a cold resistance test: after placing it at -18℃ for 7 days, take it out and melt it, and observe the changes in its physical and chemical properties.

(2) Viscosity measurement: The viscosity of each matrix formulation at 23°C and 32°C was measured using a viscometer.

(3) Thixotropy: Take an appropriate amount of gel for measurement, use rotor No. 2, and measure the viscosity by a digital viscometer. Follow the steps below: ① Gradually increase the rotation speed of the viscometer and record the viscosity at each speed; ② Gradually reduce the rotation speed of the viscometer and record the viscosity at each speed; ③ According to the pseudoplastic fluid formula D = Sn/ηn (D is the shear velocity, Sn is the shear stress, and ηn is the apparent viscosity), calculate the shear stress and draw the rising and falling curves of the shear stress at different speeds; ④ Determine the fluid properties through the rheological curve, and use the drawing software to calculate the area between the rising and falling curves as the hysteresis loop area, which is the thixotropy.

(4) Yield value: Extrapolate the rising curve of the drawn rheological curve to intersect with the vertical axis and take the strain value of the intersection.

(5) Comprehensive score: According to the importance of each indicator to the quality of the matrix, a certain weight is assigned to each indicator: 23℃ viscosity, 23℃ yield value, room temperature thixotropy, 32℃ viscosity, 32℃ yield value, and the weights are 2:2:4:1:1 respectively. Comprehensive score = 23℃ viscosity/a×20+23℃ yield value/b×20+thixotropy/c×40+32℃ viscosity/a×10+32℃ yield value/b×10. (a=maximum viscosity value, b=maximum yield value, c=maximum thixotropy).

3. Single factor investigation of gel formulation process

(1) Types of matrix excipients

Commonly used gel matrix materials are carbomer 940, carbomer 941, xanthan gum, and hydroxyethyl cellulose. Therefore, through experimental observation, the best matrix material of salvianolic acid A carbomer gel was screened out. 0.8% carbomer 940, 0.8% carbomer 941, 0.6% xanthan gum, and 1% hydroxyethyl cellulose were selected for comparative tests, and the matrix material of the gel was screened according to the index shown in "2".

Table 3 Screening of different gel matrix materials (%)

Table 4 Appearance and stability evaluation results

Gels of the above four matrix materials were prepared according to method "1". The results showed that the gel prepared with Carbomer 940 as the matrix had the following appearance: suitable odor, smooth and delicate texture, uniform application, good gloss, good spreadability, and suitable viscosity. The gel prepared with Carbomer 940 as the matrix was superior to the gels prepared with other matrices.

(2) Gel excipients and others

The evaluation index shown in "2" was used to investigate the effects of Carbomer 940 concentration, glycerol dosage, and pH on the gel forming process. The results showed that Carbomer 940 concentration, glycerol dosage, and pH all had effects on the gel forming process.

4. Orthogonal test of gel formulation process

According to the results of the single factor test, the effects of carbomer, glycerol and pH on the molding process of salvianolic acid A gel were investigated. The orthogonal test with 3 factors and 3 levels was adopted, and the yield value, appearance, thixotropy and viscosity of the gel were used as evaluation indicators to select the best molding process. The factor levels are shown in Table 2, the test results are shown in Table 3, and the variance analysis is shown in Table 4.

Table 4 Orthogonal test factor level design table

Table 5 Orthogonal test results

【Note】Kn (n＝1,2,3) is the sum of the indicators at each level of each factor. For example, K1 represents the sum of the values of the comprehensive test scores corresponding to the "1" level, and K2 and K3 are similar. Range R＝max{K1，K2，K3}-min{K1，K2，K3}). The higher K is, the better the score of the corresponding level is, and the higher R is, the greater the influence of the corresponding factor is.

Table 6 Orthogonal ANOVA

^R2 ＝0.999

*p<0.05, **p<0.005

From Tables 3, 4, and 5, we can see that the primary and secondary factors affecting product quality are A>B>C according to the comparison of the range R values; and in the factor A column, the K1 value corresponding to the "2" level is the largest, so A2 is selected, and B2 and C3 are selected by analogy, so A2B2C3 is the best preparation process. Factors A, B, and C have significant effects on the quality of the gel matrix.

When the percentage of Carbomer 940 is less than or equal to 0.4%, the formed gel has strong fluidity and low viscosity, which is not suitable for application; when the percentage of Carbomer 940 is greater than or equal to 1.2%, the formed gel has low fluidity and high viscosity, which is not suitable for application; when the amount of glycerol is small, the moisturizing effect of the gel is poor, and if the amount is greater than 20mL, the gel will be in a relatively sticky state, and the cost is high; when the pH value is less than 5, the gel has poor formability, and when the pH is greater than 7, it is alkaline, which is not conducive to the presence of salvianolic acid A, and is not suitable for maintaining a normal pH environment on the skin surface. Too high or too low will cause greater irritation to the skin. Therefore, the optimal preparation process of salvianolic acid A carbomer gel was finally confirmed to be: 0.8% Carbomer 940, 20mL glycerol, 1% vitamin C, triethanolamine adjusted to pH 6-7, and deionized water filled to 100mL.

Experimental results:

The results show that the salvianolic acid A carbomer gel prepared by the present invention is light yellow, crystal clear, has suitable viscosity, uniform color, and contains a small amount of bubbles, as shown in FIG4 .

The stability test results show that the physical properties of the carbomer gel matrix of the present invention are stable and have no obvious changes. Specifically, in the thermal acceleration test, the gel matrix has no obvious stratification and precipitation, indicating that the matrix has good uniformity; in the heat resistance test, the gel matrix remains colorless, crystal clear and viscous, indicating good heat resistance; in the cold resistance test, after the gel matrix is taken out and melted after being placed for 7 days, the matrix remains crystal clear, indicating good cold resistance.

Example 3: Salvianolic acid A carbomer gel effectively treats the imiquimod-induced psoriasis model in mice.

Experimental methods:

1. Experimental animals: C57/B6J male mice, 6-8 weeks, 20g-26g.

2. Experimental methods:

Take normal 6-8 week old C57/B6J male mice and anesthetize them by intraperitoneal injection of 200-300 μl of Avertin anesthetic according to body weight. Shave the hair on the back of the mice to form an exposure area of about 2 cm × 2 cm. Randomly and evenly group them according to body weight and exposure area, with 6 mice in each group. Shaving was performed 1-2 days before the formal experiment. Weigh the mice regularly every day, observe local skin changes, take photos and record them, and give a score of 0-3 according to the psoriasis area and disease severity index (PASI) scoring standard. The first day was recorded as 0 points. Finally, apply imiquimod cream. Except for the normal control group, other groups applied 62.5 mg of imiquimod cream on the shaved skin:

3.125mg (5%)/mouse, once a day for 4 consecutive days. And given corresponding treatment. Group 1: normal group (sham), blank control, no treatment; Group 2: matrix group (IMQ + 0% SAA), given imiquimod and smeared gel matrix on the back; Group 3: low concentration administration group (IMQ + 0.05% SAA), given imiquimod and smeared 0.05mg/g of salvianolic acid A gel on the back; Group 4: high concentration administration group (IMQ + 0.1% SAA), given imiquimod and smeared 0.1mg/g of salvianolic acid A gel on the back. The medication groups were given according to the dosage, twice a day, and each application was about 60mg.

After 4 days, samples were collected and photographed to record the skin condition on the back of the mice. Blood was collected from the eyeballs, and serum was separated and stored at -80°C. The skin lesions were removed from the subcutaneous fat tissue and divided into two parts. One part was fixed in 4% paraformaldehyde solution for preparing paraffin sections, and the other part was used for RNA extraction and stored at -80°C.

3. Evaluation method:

The following mouse PASI criteria were established with reference to the PASI (Psoriasis area and severity index) standard to evaluate clinical severity: erythema; infiltration; scaling. Each feature was evaluated with a score of 0-3: 0 = none; 1 = mild; 2 = moderate; 3 = severe. Each site was scored according to the following three clinical characteristics of skin lesions:

Erythema (E): Red or dark red inflammatory plaques that fade when pressed. 0 - no erythema visible; 1 - light red; 2 - red; 3 - very dark red.

Infiltration (I): The lesion has a tendency to spread in all directions, with blurred borders and a sense of substance when pressed. 0 - The lesion is flush with the normal skin; 1 - The lesion is slightly higher than the normal skin surface; 2 - Moderately raised, with round or sloped edges; 3 - The lesion is highly thickened and the raised area is very obvious.

Desquamation/squama (D): refers to the flaking of epidermal cells. 0-No visible scales on the surface; 1-Part of the lesions are covered with scales, mainly fine scales; 2-Most of the lesions are completely or incompletely covered with scales, and the scales are flaky;

3-The entire surface of the lesions is covered with scales, which are very thick and layered.

Exudation, dryness, and itching were not included in the total score.

Experimental results:

The salvianolic acid A gel provided by the invention has a good therapeutic effect on psoriasis.

As shown in Figure 5, compared with the application of carbomer gel base, the application of 0.05% and 0.1% salvianolic acid A gel can significantly improve imiquimod-induced psoriasis-like inflammatory skin lesions and reduce epidermal thickening without obvious toxic side effects, showing certain effectiveness and safety.

Example 4: Evaluation of the irritation of salvianolic acid A carbomer gel

Experimental methods:

1. Experimental animals: C57/B6J male mice, 6-8 weeks, 20g-26g.

2. Experimental methods:

The treatment method was the same as above, and the groups were divided into: Group 1: normal group (sham), blank control, no treatment; Group 2: normal + matrix group (0% SAA), only about 60 mg of gel matrix was applied on the back; Group 3: normal + drug administration group (0.1% SAA), about 60 mg of 0.1% salvianolic acid A gel was applied on the back; Group 4: model group (IMQ), imiquimod was given; Group 5: IMQ + matrix group (IMQ

+0% SAA), imiquimod was administered and the gel matrix was applied to the back. The medication group was given according to the dose, twice a day, and about 60

mg.

Experimental results:

The salvianolic acid A carbomer gel provided by the invention has mild effect, moisturizing effect and no irritation to the skin.

1. The present invention is non-irritating to damaged skin and exhibits a certain moisturizing effect:

As shown in Figure 6, compared with the model group (IMQ), the skin PASI score of the IMQ+matrix group (IMQ+0% SAA) decreased on the fourth day, indicating that the symptoms began to alleviate and recover, and there was a significant improvement compared with the IMQ group, indicating that the carbomer gel matrix in the present invention is mild, non-irritating and moisturizing, and has obvious advantages in treating and improving skin injury diseases.

2. Blank gel matrix and medicated gel are non-irritating to the skin:

As shown in FIG6 , there was no significant difference in skin PASI score, weight change, and epidermal thickening between the normal+matrix group (0% SAA) and the normal group (sham), indicating that the carbomer gel matrix of the present invention itself is non-irritating to the skin, has no obvious toxic side effects, and exhibits a certain degree of safety.

As shown in FIG6 , there was no significant difference between the normal + drug administration group (0.1% SAA) and the normal group (sham) in the skin PASI score, weight change, and epidermal thickening, indicating that the active ingredients, salvianolic acid A and the carbomer gel matrix, in the salvianolic acid A carbomer gel preparation of the present invention are non-irritating to the skin, have no obvious toxic side effects, and exhibit a certain degree of safety.

Example 5 Transdermal delivery for the treatment of imiquimod-induced psoriasis in mice is a more effective route of administration than intraperitoneal injection.

Experimental methods:

1. Experimental animals: C57/B6J male mice, 6-8 weeks, 20g-26g.

2. Experimental methods: The treatment method was the same as above, and the groups were divided into: Group 1: normal group (sham), blank control, no treatment; model group (IMQ), given imiquimod; Group 3: intraperitoneal injection group (IMQ + intraperitoneal injection of 4 mg/kg SAA), given imiquimod and intraperitoneal injection of 4 mg/kg

(equivalent to 0.1% SAA gel) salvianolic acid A solution; Group 4: low concentration administration group (IMQ + 0.05% SAA), given imiquimod and smeared on the back with 0.05mg/g salvianolic acid A gel; Group 5: high concentration administration group (IMQ + 0.1% SAA), given imiquimod and smeared on the back with 0.1mg/g salvianolic acid A gel. The medication group was administered according to the dose, twice a day, with each application of about 60mg; the intraperitoneal injection group was administered according to the dose, twice a day, with each injection of about 100μl.

Experimental results:

Compared with intraperitoneal injection, transdermal delivery of the salvianolic acid A carbomer gel in the present invention in treating the imiquimod-induced mouse psoriasis model showed a more obvious therapeutic effect.

As shown in Figure 7C and D, the skin PASI scores and epidermal thickness of the two different concentrations of drug administration groups on days 2-4 were lower than those of the intraperitoneal injection group, indicating that applying salvianolic acid A carbomer gel has a better therapeutic effect than intraperitoneal injection of 4 mg/kg SAA, indicating that the present invention is a more optimal SAA skin targeted delivery preparation.

Example 6 Salvianolic acid A carbomer gel effectively treats the ultraviolet-induced photodamage model in mice.

Experimental methods:

1. Experimental animals: 30 female BALB/c mice, 6-8 weeks old, body weight, 18g-20g.

2. Experimental equipment: SIGMA SS07-T cell irradiation device, UVB lamp, power 0.0028J/s

Experimental method: Carbomer gels with salvianolic acid A content of 0.5‰, 2.5‰, and 5‰ were prepared according to Example 1.

After sodium pentobarbital anesthesia, shave the back, 2cm*2cm. After shaving, evenly group the mice according to weight and exposed area. Before irradiation: score, anesthetize, weigh. Irradiation: After anesthetizing the mice, place them under UVB lamp for 3 minutes. After irradiation: Apply SAA Carbopol gel, 30ul per mouse (about the size of a mung bean, about a thin layer on the back), twice a day. Once after irradiation and once the next morning. Record the weight and score of the mice every day. Grouping: Group 1: Normal group, blank control (Sham), no treatment; Group 2: Model group, UVB irradiation, and application of matrix (UVB); Group 3: UVB + positive drug group (UVB + Positive): UVB irradiation, and application of aloe vera gel (Positive); Group 4: 0.5‰ SAA treatment group (UVB + 0.5‰ SAA): UVB irradiation, and application of 0.5‰ SAA gel; Group 5: 2.5‰ SAA treatment group (UVB + 2.5‰ SAA): UVB irradiation, and application of 2.5‰ SAA gel; Group 6: 5‰

SAA treatment group (UVB+5‰SAA): UVB irradiation and application of 5‰SAA gel.

Experimental results:

The salvianolic acid A gel provided by the invention has a good therapeutic effect on ultraviolet damage caused by UVB.

As shown in Figure 8, compared with applying carbomer gel matrix, applying 0.5‰, 2.5‰ and 5‰ of salvianolic acid A gel can improve UVB-induced inflammatory skin lesions and reduce epidermal thickening in a dose-dependent manner, without obvious toxic side effects, showing certain effectiveness and safety. The effect is significant compared with aloe vera gel on the market.

Claims (4)

1. a kind of salvianolic acid A carbomer gel, described salvianolic acid A carbomer gel, salvianolic acid A, carbomer 940, glycerin, triethanolamine, vitamin C and deionized water . 2. a kind of salvianolic acid A carbomer gel according to claim 1, is characterized in that, each composition of described gel is made by following weight percentage: salvianolic acid A 0.001%-10% , Carbomer 940 0.1%-3.0%, glycerin 20%, triethanolamine adjusted to pH 6-11, vitamin C 0.01%-1%, the balance is deionized water. 3. the application of a kind of salvianolic acid A carbomer gel according to claim 1 and 2 in the preparation of medicine for the treatment of skin diseases or improvement of skin medicine. 4. according to the described application of claim 3, it is characterized in that, described skin disease comprises psoriasis, contact dermatitis, diabetic dermatitis, allergic dermatitis, atopic dermatitis, stasis dermatitis, seborrheic dermatitis, eczema , Rubella, urticaria, acne, pimples, UV damage, sunburn, diabetic foot, wounds, burns.

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