The application of salvianolic acid B in the preparation of a medicament for treating atopic dermatitis, and an ointment and a preparation method thereof

Abstract

The application discloses a kind of to adopt salvianolic acid B as preparation treatment atopy dermatitis drug application and its ointment and preparation method, belong to biomedical technology field, the ointment includes following raw materials: salvianolic acid B, magnesium citrate, soybean lecithin, vaseline, xanthan gum, ascorbic acid, glycerol, β-cyclodextrin, by cyclodextrin embedding active ingredient salvianolic acid B, and preparation is into water-in-oil type ointment, good stability, easy absorption, salvianolic acid B is easily degraded, and the problem that low liposolubility leads to poor absorption, poor curative effect is solved.Active ingredient salvianolic acid B in ointment is by inhibiting thymic stromal lymphopoietin (TSLP) production and then significantly inhibits the occurrence and development of atopic dermatitis, can effectively treat atopic dermatitis, especially for obese atopic dermatitis patient has good therapeutic effect.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical technology, and particularly relates to an application of salvianolic acid B in preparation of a medicament for treating atopic dermatitis, a salve and a preparation method thereof. BACKGROUND

[0002] Atopic dermatitis is a chronic, inflammatory skin disease with recurrent episodes, and is clinically manifested as recurrent episodes of eczematous dermatitis accompanied by severe itching, which seriously affects the physical and mental health of patients. The global prevalence of atopic dermatitis is increasing year by year, and more and more patients and families are suffering from atopic dermatitis. It is of great clinical significance to actively explore drugs for preventing and treating atopic dermatitis.

[0003] The main goal of atopic dermatitis treatment is to reduce the inducing or aggravating factors, relieve clinical symptoms, delay and prevent recurrence, reduce complications, and improve the quality of life of patients. At present, patients with mild to moderate atopic dermatitis are treated with topical calcineurin inhibitors (TCI) and topical corticosteroids (TCS), and patients with severe atopic dermatitis are treated with systemic immunosuppressive agents or biological agents. However, TCI can cause local irritation, and some patients cannot tolerate it and stop taking it. External TCS can increase the risk of skin atrophy, especially in the skin folds; and a large amount of external TCS can increase systemic absorption, especially in children, which can cause growth and development inhibition. For patients with severe atopic dermatitis, systemic treatment is generally used, including biological agents targeting IL-4 and IL-13 pathways and small molecule inhibitors targeting JAK-STAT pathways. Biological agents have the potential risk of inducing immune disorders, causing other immune diseases or tumors; the JAK-STAT pathway is the main signal pathway of various cytokines and growth factors, and is widely expressed and involved in cell proliferation, differentiation, migration, apoptosis and other biological processes. There is a potential unknown risk of treating atopic dermatitis by JAK inhibitors, and its adverse reactions still need long-term observation. Therefore, it is still urgent to actively explore safe and effective drugs for treating atopic dermatitis. In addition, current studies have found that obese patients have treatment resistance to traditional treatment methods, for example, studies have found that obese patients have poor treatment response to dupilumab targeting IL-4 and IL-13 signaling pathways. Due to the high incidence of atopic dermatitis and the relatively large base of obese population, there is still a lack of effective drugs for individualized treatment of obese population.

[0004] Salvianolic acid B (SAB) is one of the main components of Danshen, and is mainly used for treating cardiovascular diseases due to its antioxidant, anti-inflammatory and antitumor effects. We have conducted more in-depth research on salvianolic acid B to expand its use in other disease fields. However, salvianolic acid B is prone to degradation and has low lipid solubility, which leads to poor efficacy and poor absorption of the prepared drug. SUMMARY

[0005] In view of this, the purpose of the present application is to provide a kind of application of salvianolic acid B as preparation treatment atopic dermatitis drug and its ointment and preparation method, expand the use of salvianolic acid B in the treatment of other diseases, solve the problem of poor drug efficacy and poor absorption of salvianolic acid B in the preparation of drug due to its easy degradation and low liposolubility.

[0006] The present application solves the above technical problems by the following technical means:

[0007] A kind of application of salvianolic acid B as preparation treatment atopic dermatitis drug.

[0008] TSLP is a key molecule for mediating type 2 inflammation, an important start molecule for inducing atopic dermatitis, and inhibiting the expression of TSLP is of great significance for inhibiting the expression of downstream Th2 type (IL-4, IL-5, IL-13) inflammatory factors, inhibiting the activation of basophilic granulocytes, and then inhibiting the inflammation of atopic dermatitis, and we first found that salvianolic acid B can significantly inhibit the occurrence and development of atopic dermatitis by inhibiting the production of TSLP.

[0009] Further, the application includes the application in treating obese atopic dermatitis patients.

[0010] We found that the inflammation of atopic dermatitis in obese mice is more serious, and the expression of TSLP is higher, and external use of salvianolic acid B can significantly inhibit the inflammation of atopic dermatitis, especially for the atopic dermatitis inflammation of obese patients.

[0011] The present application also discloses an ointment for treating atopic dermatitis by using salvianolic acid B as preparation.

[0012] Further, the ointment also includes pharmaceutically acceptable ointment adjuvants.

[0013] By adding adjuvants to salvianolic acid B to prepare an ointment with good liposolubility, good permeability and easy absorption, the ointment can be fully absorbed by the skin when used, and atopic dermatitis can be better treated.

[0014] Further, the ointment includes the following raw materials:

[0015] Salvianolic acid B, magnesium citrate, beta-cyclodextrin, soybean lecithin, vaseline, xanthan gum, ascorbic acid, glycerol, deionized water.

[0016] Further, the mass percentage of each component in the ointment is as follows: 2-5% salvianolic acid B, 1-2% magnesium citrate, 15-20% beta-cyclodextrin, 3-5% soy lecithin, 25-30% vaseline, 5-8% xanthan gum, 1-5% ascorbic acid, 8-10% glycerol, and the balance is deionized water.

[0017] The application also discloses a preparation method of the ointment for treating atopic dermatitis by using salvianolic acid B as a preparation medicine.

[0018] A. salvianolic acid B is mixed with magnesium citrate, and then stirred uniformly in distilled water, and then sodium carbonate is added to adjust the pH to 4 to obtain a salvianolic acid B mixture for standby;

[0019] B. 15wt% beta-cyclodextrin solution is prepared by adding distilled water to beta-cyclodextrin, and then the salvianolic acid B mixture in step A is added to the beta-cyclodextrin solution, ultrasonic treatment is carried out for 50-60min, vacuum freeze drying is carried out after the ultrasonic treatment is completed, and then grinding is carried out to obtain salvianolic acid B cyclodextrin embedding material for standby;

[0020] C. vaseline, xanthan gum and soy lecithin are mixed, and then placed in a homogenizer, and homogenized at 60-70 DEG C and 2000-3000r / min for 8-15min to obtain an oil phase for standby;

[0021] D. glycerol and ascorbic acid are mixed, and then mixed uniformly in deionized water, and stirred and dispersed to be transparent to obtain W2 aqueous phase; the W2 aqueous phase is added to the oil phase in step C, and stirred at a speed of 1000-2000r / min for 8-15min, so that the W2 aqueous phase is completely coated in the oil phase, and then placed in a homogenizer and homogenized at a speed of 3000r / min for 8-13min to obtain a water-in-oil type mixture for standby;

[0022] E. deionized water is mixed with xanthan gum, and then stirred uniformly, and then the water-in-oil type mixture in step D is slowly added, and stirred at a high speed of 1000r / min for 3-5min, and then the salvianolic acid B cyclodextrin embedding material in step A is added, and stirred until uniformly dispersed to obtain a water-in-oil-in-water type ointment.

[0023] Salvianolic acid B is easy to degrade and has low fat solubility, so that it is easy to degrade and not easy to absorb when preparing a medicine, and thus the curative effect is reduced, and therefore it is necessary to treat salvianolic acid B in the process of preparing a medicine to improve the stability and absorbability of salvianolic acid B, so as to improve the curative effect.

[0024] The magnesium citrate and salvianolic acid B are mixed and dissolved, the salvianolic acid B reacts with the magnesium citrate to generate a stable complex, and then the stability of the salvianolic acid B is improved, and degradation of the salvianolic acid B is inhibited; further, the salvianolic acid B is embedded by the beta-cyclodextrin, the salvianolic acid B is loaded on the beta-cyclodextrin, degradation of the salvianolic acid B is inhibited, and the stability of the salvianolic acid B is significantly increased by the joint action of the magnesium citrate and the beta-cyclodextrin, and degradation of the salvianolic acid B is inhibited.

[0025] The vaseline, xanthan gum and soybean lecithin in step C are prepared into an oil phase, and then added into the W2 water phase in step D to prepare a water-in-oil mixture, and then added into step E to prepare a water-in-oil-in-water ointment, so that the ointment has the advantages of both water-in-oil and oil-in-water drugs, the penetration rate of the active ingredient is increased, the active ingredient can quickly penetrate the epidermis, the concentration of the active ingredient delivered to the bottom layer of the skin is increased, and the absorption rate of the active ingredient is increased, thereby solving the problems of low liposolubility and low absorption of salvianolic acid B in the preparation of drugs.

[0026] Further, the temperature of ultrasonic treatment in step A is 30-50 DEG C, and the power is 80-100 W.

[0027] Further, the conditions of vacuum freeze drying in step B are as follows: temperature: -20 DEG C to -10 DEG C, and vacuum degree: 13-20 Pa.

[0028] Further, the amount of xanthan gum used in steps C and E accounts for 70% and 30% of the total amount of xanthan gum, respectively.

[0029] Beneficial effects:

[0030] 1. The application of salvianolic acid B for preparing a drug for treating atopic dermatitis, and the ointment and preparation method thereof, the active ingredient is embedded by cyclodextrin, and a water-in-oil-in-water ointment is prepared, so that the ointment has good stability and is easy to absorb.

[0031] 2. The application of salvianolic acid B for preparing a drug for treating atopic dermatitis, and the ointment and preparation method thereof, salvianolic acid B is used as an active ingredient to prepare an ointment, atopic dermatitis is treated by external application, secondary immune disorders caused by monoclonal antibodies or JAK inhibitors can be avoided, and the risk of other immune diseases can be reduced.

[0032] 3. The ointment prepared by the application of salvianolic acid B for preparing a drug for treating atopic dermatitis has a significant therapeutic effect on the aggravation of atopic dermatitis in obese patients, and solves the problem of treatment resistance of obese patients to traditional atopic dermatitis treatment methods. DETAILED DESCRIPTION

[0033] Figure 1 : results of constructing an atopic dermatitis mouse model;

[0034] Figure 2 Figure 7 shows the results of treating atopic dermatitis in Lean and Obese mice with Salvianolic acid B, where Figure E shows the number of dermal infiltrating inflammatory cells in Lean and Obese mice. DETAILED DESCRIPTION

[0035] The present application will be described in detail below with reference to specific embodiments and drawings:

[0036] It has been found in the current study that obese patients have resistance to traditional treatment methods, for example, obese patients have poor response to dupilumab targeting IL-4 and IL-13, and our experimental study has found that Salvianolic acid B not only has good treatment effect on atopic dermatitis, but also shows significant treatment effect in the treatment experiment of obese mice. Salvianolic acid B can significantly inhibit the occurrence and development of atopic dermatitis, and has good treatment effect on the aggravation of atopic dermatitis related to obesity, and the specific experiments are as follows:

[0037] Experiment 1:

[0038] 1. Construction of obese mouse model: 6-week-old C57BL / 6 mice were selected as experimental objects and divided into Obese group (obese mice) and Lean group (normal mice), Obese mice were fed with high-fat feed (60% kcal), Lean mice were fed with ordinary feed (10% kcal), and were continuously fed for 16 weeks for standby.

[0039] 2. Construction of atopic dermatitis model: Obese and Lean mice were given 2 nmol of MC903 on the ear skin for continuous smearing to construct atopic dermatitis model. The mice were photographed and the ear thickness was measured on the 10th day; the peripheral serum of the mice was collected for detecting the levels of TSLP and IgE; 1 mm x 1 cm size ear tissue was formalin soaked for HE staining; 1 / 4 ear tissue was used for qRT-PCR to detect the expression of inflammatory molecules in the skin lesions, and the data obtained are shown in Figure 1 Figure 1 The control group is the group without smearing MC903, and the MC903 group is the group smearing MC903.

[0040] ​3. Treatment of Atopic Dermatitis: The treatment group (MC903+SAB) was simultaneously treated with topical salvianolic acid B in mice to treat atopic dermatitis. Salvianolic acid B was dissolved in corn oil to prepare a 34.8 μM solution, which was applied to the mice at a rate of 30 μL per application, once daily. After 10 consecutive days of application, the mice were photographed and ear thickness was measured. Peripheral serum was collected from the mice to detect TSLP and IgE levels. A 1 mm × 1 cm ear tissue sample was soaked in formalin and stained with hematoxylin and eosin (HE). One-quarter of the ear tissue was used for qRT-PCR to detect the expression of inflammatory molecules in the skin lesions. The data obtained are as follows: Figure 2 As shown.

[0041] 4. Analysis of experimental results:

[0042] (1) According to Figure 1 It can be seen that: the condition of mice after using MC903 was as follows: (1) MC903 mice showed obvious redness and swelling, and HE staining showed obvious inflammatory cell infiltration, which was more severe in Obese mice. Figure 1 (A) ;(2) MC903 mice scratched more frequently, and Obese mice scratched even more frequently. Figure 1 (B) ;(3) Ear thickness and epidermal thickening increased in MC903 mice, and the difference was more obvious in Obese mice. Figure 1 (C, D); (4) The number of dermal infiltrating inflammatory cells was significantly increased in MC903 mice, and even more infiltrating cells were found in Obese mice. Figure 1 (5) Peripheral blood TSLP and IgE levels were significantly increased in MC903 mice, with even more significant differences in Obese mice. Figure 1 (6) After topical application of MC903, the expression levels of IL-1β, IL-4, IL-5, IL-13 and TSLP in mouse skin tissue were significantly increased. Figure 1 The expression of inflammatory molecules in Obese mice was further increased. These results indicate that an atopic dermatitis mouse model was successfully constructed by applying MC903, and that the atopic dermatitis inflammation in Obese mice was more severe compared with that in Lean mice.

[0043] (2) According to Figure 2 It can be seen that: the mice treated with tanshinone B showed the following results: Lean mice and Obese mice (1): redness and swelling were reduced, and the number of infiltrating inflammatory cells stained with HE was reduced: ( Figure 2 (A) ;(2) The number of scratches decreased ( Figure 2 (B) ;(3) Ears are thickened, and the epidermis is thickened and thinned ( Figure 2 (C, D); (4) Peripheral blood TSLP and IgE levels were significantly reduced ( Figure 2 (5) The expression levels of TSLP, IL-4, IL-5, and IL-13 in mouse tissues were significantly reduced.Figure 2 : G); the above results show that salvianolic acid B can significantly inhibit atopic dermatitis inflammation, and has a significant therapeutic effect on the aggravation of atopic dermatitis inflammation in obese mice.

[0044] Example 1: Preparation of ointment

[0045] Salvianolic acid B 60g, magnesium citrate 30g, soybean lecithin 80g, vaseline 540g, xanthan gum 120g, ascorbic acid 60g, glycerol 180g, β-cyclodextrin 340g, and deionized water 590g were weighed.

[0046] Preparation method:

[0047] A. After mixing salvianolic acid B and magnesium citrate, 450g of distilled water was added and stirred uniformly. After adjusting the pH to 4 by adding sodium carbonate, a salvianolic acid B mixture was obtained for standby;

[0048] B. A 15wt% β-cyclodextrin solution was prepared by adding distilled water to β-cyclodextrin. Then the salvianolic acid B mixture was added to the β-cyclodextrin solution, and ultrasonic treatment was carried out at a temperature of 40℃ and a power of 90W for 55min. After ultrasonic treatment, vacuum freeze-drying was carried out at a temperature of -15℃ and a vacuum degree of 16Pa, and then salvianolic acid B cyclodextrin embedding material with a particle size of about 15μm was obtained for standby;

[0049] C. Vaseline, 84g of xanthan gum, and soybean lecithin were mixed and placed in a homogenizer for homogenization at 65℃ and 2500r / min for 11min to obtain an oil phase for standby;

[0050] D. Glycerol and ascorbic acid were mixed and then 177g of deionized water was added and mixed uniformly. After stirring and dispersing to transparency, W2 aqueous phase was obtained. The W2 aqueous phase was added to the oil phase in step C, and stirred at a speed of 1500r / min for 12min to make the W2 aqueous phase completely coated in the oil phase. Then it was placed in a homogenizer and homogenized at a speed of 3000r / min for 10min to obtain a water-in-oil type mixture for standby;

[0051] E. The remaining 413g of deionized water was mixed with the remaining 36g of xanthan gum, and then the water-in-oil type mixture in step D was slowly added. After stirring at a high speed of 1000r / min for 4min, the salvianolic acid B cyclodextrin embedding material in step A was added and stirred until it was uniformly dispersed to obtain a water-in-oil-in-water type ointment.

[0052] Example 2: Preparation of ointment

[0053] Salvianolic acid B 40g, magnesium citrate 20g, soybean lecithin 60g, vaseline 500g, xanthan gum 100g, ascorbic acid 20g, glycerol 160g, β-cyclodextrin 300g, and deionized water 800g were weighed.

[0054] Preparation method:

[0055] A, Danpolysaccharide B and magnesium citrate were mixed and then added into 300 g distilled water to stir uniformly. After adjusting pH to 4 by adding sodium carbonate, Danpolysaccharide B mixture was obtained for standby;

[0056] B, 15 wt% β-cyclodextrin solution was prepared by adding distilled water into β-cyclodextrin. Then Danpolysaccharide B mixture was added into the β-cyclodextrin solution. Ultrasonic treatment was performed at 30℃ and 80W for 50 min. After ultrasonic treatment, vacuum freeze-drying was performed at -20℃ and 13 Pa vacuum degree. Then Danpolysaccharide B cyclodextrin inclusion was obtained by grinding to a particle size of about 20 μm for standby;

[0057] C, vaseline, 70 g xanthan gum and soybean lecithin were mixed and then placed in a homogenizer for homogenization at 60℃ and 2000 r / min for 8 min to obtain oil phase for standby;

[0058] D, glycerol and ascorbic acid were mixed and then added into 240 g deionized water to mix uniformly. After stirring and dispersing to be transparent, W2 aqueous phase was obtained. W2 aqueous phase was added into the oil phase in step C. After stirring at 1000 r / min for 8 min, W2 aqueous phase was completely coated in the oil phase. Then the mixture was placed in a homogenizer for homogenization at 3000 r / min for 8 min to obtain water-in-oil mixture for standby;

[0059] E, the remaining 560 g deionized water was mixed with the remaining 30 g xanthan gum to stir uniformly. Then the water-in-oil mixture in step D was slowly added. After stirring at 1000 r / min for 3 min, Danpolysaccharide B cyclodextrin inclusion in step A was added to stir to disperse uniformly to obtain water-in-oil-in-water type ointment.

[0060] Example 3: Preparation of ointment three

[0061] Danpolysaccharide B 100 g, magnesium citrate 40 g, soybean lecithin 100 g, vaseline 600 g, xanthan gum 160 g, ascorbic acid 100 g, glycerol 200 g, β-cyclodextrin 400 g and deionized water 300 g were weighed.

[0062] Preparation method:

[0063] A, Danpolysaccharide B and magnesium citrate were mixed and then added into 700 g distilled water to stir uniformly. After adjusting pH to 4 by adding sodium carbonate, Danpolysaccharide B mixture was obtained for standby;

[0064] B, 15wt% β-cyclodextrin solution was prepared by adding distilled water into β-cyclodextrin, then the mixture of salvianolic acid B was added into the β-cyclodextrin solution, and the mixture was ultrasonically treated at 50℃ and 100W for 60min, and then vacuum freeze-drying was carried out at -10℃ and 20Pa, and finally the salvianolic acid B cyclodextrin inclusion was obtained by grinding to a particle size of about 25μm;

[0065] C, the vaseline, 112g xanthan gum and soybean lecithin were mixed and then placed in a homogenizer to be homogenized at 70℃ and 3000r / min for 15min to obtain the oil phase;

[0066] D, the glycerol and ascorbic acid were mixed and then added into 90g deionized water to be mixed uniformly, and then dispersed and stirred to be transparent to obtain W2 aqueous phase; the W2 aqueous phase was added into the oil phase in step C, and stirred at 2000r / min for 15min to make the W2 aqueous phase completely coated in the oil phase, and then placed in a homogenizer to be homogenized at 3000r / min for 13min to obtain the water-in-oil mixture;

[0067] E, the remaining 210g deionized water and the remaining 48g xanthan gum were mixed and then stirred uniformly, and then the water-in-oil mixture in step D was slowly added, and stirred at 1000r / min for 5min, and then the salvianolic acid B cyclodextrin inclusion in step A was added and stirred to be uniformly dispersed to obtain the water-in-oil-in-water ointment.

[0068] Comparative Example 1: Preparation of ointment

[0069] In comparison with Example 1, the only difference is that no magnesium citrate is added during the preparation of the ointment.

[0070] Salvianolic acid B 60g, soybean lecithin 80g, vaseline 540g, xanthan gum 120g, ascorbic acid 60g, glycerol 180g, β-cyclodextrin 340g and deionized water 590g were weighed.

[0071] Preparation method:

[0072] A, 300g distilled water was added into salvianolic acid B and stirred uniformly, and then sodium carbonate was added to adjust the pH to 4 to obtain the salvianolic acid B mixture B for standby;

[0073] B, 15wt% β-cyclodextrin solution was prepared by adding distilled water into β-cyclodextrin, then the mixture of salvianolic acid B was added into the β-cyclodextrin solution, and the mixture was ultrasonically treated at 40℃ and 90W for 55min, and then vacuum freeze-drying was carried out at -15℃ and 16Pa, and finally the salvianolic acid B cyclodextrin inclusion was obtained by grinding to a particle size of about 15μm;

[0074] C. Mix the vaseline, 84 g xanthan gum, and soybean lecithin, and then place them in a homogenizer and homogenize at 65°C and 2500 r / min for 11 min to obtain an oil phase, which is ready for use;

[0075] D. Mix the glycerol and ascorbic acid, and then add 177 g of deionized water to mix them evenly. Stir and disperse until transparent to obtain a W2 aqueous phase. Add the W2 aqueous phase to the oil phase in step C, and stir at a speed of 1500 r / min for 12 min until the W2 aqueous phase is completely coated in the oil phase. Then place it in a homogenizer and homogenize at a speed of 3000 r / min for 10 min to obtain a water-in-oil mixture, which is ready for use;

[0076] E. Mix the remaining 413 g of deionized water and the remaining 36 g of xanthan gum, and then slowly add the water-in-oil mixture in step D. Stir at a high speed of 1000 r / min for 4 min, and then add the salvianolic acid B cyclodextrin inclusion compound in step A. Stir until evenly dispersed to obtain an oil-in-water-in-water ointment.

[0077] Comparative Example 2: Preparation of an ointment

[0078] In contrast to Example 1, the only difference is that no β-cyclodextrin is used for embedding during the preparation of the ointment.

[0079] Take salvianolic acid B 60 g, magnesium citrate 30 g, soybean lecithin 80 g, vaseline 540 g, xanthan gum 120 g, ascorbic acid 60 g, glycerol 180 g, and deionized water 590 g.

[0080] Preparation method:

[0081] A. Mix salvianolic acid B and magnesium citrate, and then add 450 g of distilled water to stir them evenly. Add sodium carbonate to adjust the pH to 4 to obtain a salvianolic acid B mixture, which is ready for use;

[0082] B. Vacuum freeze-dry the salvianolic acid B mixture at a temperature of -15°C and a vacuum degree of 16 Pa, and then grind it into a salvianolic acid B mixture with a particle size of about 15 μm, which is ready for use;

[0083] C. Mix the vaseline, 84 g xanthan gum, and soybean lecithin, and then place them in a homogenizer and homogenize at 65°C and 2500 r / min for 11 min to obtain an oil phase, which is ready for use;

[0084] D. Mix the glycerol and ascorbic acid, and then add 177 g of deionized water to mix them evenly. Stir and disperse until transparent to obtain a W2 aqueous phase. Add the W2 aqueous phase to the oil phase in step C, and stir at a speed of 1500 r / min for 12 min until the W2 aqueous phase is completely coated in the oil phase. Then place it in a homogenizer and homogenize at a speed of 3000 r / min for 10 min to obtain a water-in-oil mixture, which is ready for use;

[0085] E, the remaining 413 g of deionized water and the remaining 36 g of xanthan gum were mixed and stirred until uniform, then the water-in-oil mixture in step D was slowly added, stirred at 1000 r / min for 4 min, then the salvianolic acid B mixture in step A was added and stirred until uniform to obtain the water-in-oil-in-water ointment.

[0086] Comparative Example 3: Preparation of ointment

[0087] In contrast to Example 1, the difference is that the ointment is not prepared into water-in-oil-in-water type, but is directly mixed with raw materials to prepare the ointment.

[0088] Salvianolic acid B 60 g, magnesium citrate 30 g, soy lecithin 80 g, vaseline 540 g, xanthan gum 120 g, ascorbic acid 60 g, glycerol 180 g, β-cyclodextrin 340 g, and deionized water 590 g were weighed.

[0089] Preparation method:

[0090] A, salvianolic acid B and magnesium citrate were mixed and added to 450 g of distilled water and stirred until uniform, then sodium carbonate was added to adjust the pH to 4 to obtain salvianolic acid B mixture B for standby;

[0091] B, 15 wt% β-cyclodextrin solution was prepared by adding distilled water to β-cyclodextrin, then the salvianolic acid B mixture was added to the β-cyclodextrin solution, and ultrasonic treatment was carried out at a temperature of 40°C and a power of 90W for 55 min, then vacuum freeze-drying was carried out at a temperature of -15°C and a vacuum degree of 16 Pa, and then the salvianolic acid B cyclodextrin inclusion was ground to a particle size of about 15 μm for standby;

[0092] C, the remaining raw materials were mixed and stirred at 1000 r / min for 4 min, then the salvianolic acid B cyclodextrin inclusion in step A was added and stirred until uniform to obtain the ointment.

[0093] Comparative Example 4: In contrast to Example 1, the difference is that the ointment is prepared by mixing with conventional method, without adding magnesium citrate, without using β-cyclodextrin to embed salvianolic acid B, and without preparing into water-in-oil-in-water ointment.

[0094] Salvianolic acid B 60 g, soy lecithin 80 g, vaseline 540 g, xanthan gum 120 g, ascorbic acid 60 g, glycerol 180 g, and deionized water 590 g were weighed.

[0095] Preparation method:

[0096] A, soy lecithin, vaseline, xanthan gum, ascorbic acid, glycerol, and deionized water were mixed and stirred at 1000 r / min for 4 min, then salvianolic acid B was added and stirred until uniform to obtain the ointment.

[0097] Experiment 2: Ointment degradation measurement experiment

[0098] The degradation amount of the ointment prepared in Example 1, Comparative Examples 1-4 was measured.

[0099] The ointment prepared in Example 1, Comparative Examples 1-4 was taken 200 g respectively, and the content of salvianolic acid B therein was measured after being placed in air at room temperature for 30 days. According to the original content of salvianolic acid B in Example 1, Comparative Examples 1-4 (the content of salvianolic acid B in Example 1 was 3%, the content of salvianolic acid in Comparative Example 1 was about 3.05%, the content of salvianolic acid B in Comparative Example 2 was about 3.61%, the content of salvianolic acid B in Comparative Example 3 was 3%, and the content of salvianolic acid B in Comparative Example 4 was 3.68%), the degradation amount of salvianolic acid B was calculated, and the average data is shown in Table 1:

[0100] Table 1

[0101]

[0102] According to the data analysis of Table 1:

[0103] (1) Compared with Example 1, the degradation amount of salvianolic acid B in Comparative Example 1 was 1.22 g, which was 0.39 g higher than that in Example 1. This was because magnesium citrate was not added during the preparation of the ointment in Comparative Example 1, and the complex of salvianolic acid B was not formed to stabilize it, resulting in an increase in the degradation amount of salvianolic acid B;

[0104] (2) Compared with Example 1, the degradation amount of salvianolic acid B in Comparative Example 2 was 2.48 g, which was 1.65 g higher than that in Example 1. This was because β-cyclodextrin was not used for embedding during the preparation of the ointment in Comparative Example 2, resulting in an increase in the degradation amount of salvianolic acid B;

[0105] (3) Compared with Example 1, the degradation amount of salvianolic acid B in Comparative Example 4 was 3.24 g, which was 2.41 g higher than that in Example 1. This was because magnesium citrate was not added during the preparation of the ointment in Comparative Example 4, and β-cyclodextrin was not used for embedding, resulting in the failure of salvianolic acid B to form a stable complex and stabilize it, and the lack of protection of β-cyclodextrin leading to easy degradation, and thus a large degradation amount after being placed in air for 30 days. The data in Table 1 shows that the addition of magnesium citrate to form a stable complex with salvianolic acid B and the embedding of salvianolic acid B with β-cyclodextrin can effectively inhibit the degradation of salvianolic acid B.

[0106] The above examples are only used to illustrate the technical solutions of the present application but not limit the present application. Although the present application is described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or equivalently replaced without departing from the purpose and scope of the present application, and all should be covered in the scope of the claims of the present application. The technical, shape and structure parts not described in detail in the present application are all known technologies.

Claims

1. The use of salvianolic acid B for the preparation of a medicament for treating atopic dermatitis, characterized in that, The application is the application for treating atopic dermatitis patients.

2. A method for preparing a treatment ointment for atopic dermatitis by using salvianolic acid B, characterized in that, The mass percentage of each component in the ointment is as follows: Salvianolic acid B 2-5%, magnesium citrate 1-2%, β-cyclodextrin 15-20%, soybean lecithin 3-5%, vaseline 25-30%, xanthan gum 5-8%, ascorbic acid 1-5%, glycerol 8-10%, and the balance is deionized water; The preparation method is as follows: A. Mix salvianolic acid B and magnesium citrate, then add distilled water and stir until uniform, then add sodium carbonate to adjust the pH to 4 to obtain a salvianolic acid B mixture for standby; B. Add distilled water to β-cyclodextrin to prepare a 15wt% β-cyclodextrin solution, then add the salvianolic acid B mixture in step A to the β-cyclodextrin solution, ultrasonic treatment for 50-60 min, vacuum freeze-drying after ultrasonic treatment, then grinding to obtain salvianolic acid B cyclodextrin inclusion for standby; C. Mix vaseline, xanthan gum, and soybean lecithin, then place them in a homogenizer and homogenize at 60-70°C and 2000-3000 r / min for 8-15 min to obtain an oil phase for standby; D. Mix glycerol and ascorbic acid, then add deionized water and mix until uniform, then stir and disperse until transparent to obtain W2 aqueous phase; add the W2 aqueous phase to the oil phase in step C, stir at a speed of 1000-2000 r / min for 8-15 min, then place it in a homogenizer and homogenize at a speed of 3000 r / min for 8-13 min to obtain a water-in-oil mixture for standby; E. Mix deionized water and xanthan gum, then stir until uniform, then add the water-in-oil mixture in step D, stir at a high speed of 1000 r / min for 3-5 min, then add the salvianolic acid B cyclodextrin inclusion in step B, stir until dispersed uniformly to obtain a water-in-oil-in-water ointment.

3. The method for preparing the ointment for treating atopic dermatitis by adopting salvianolic acid B according to claim 2, characterized in that, The temperature for ultrasonic treatment in step B is 30-50°C, and the power is 80-100W.

4. The method for preparing the ointment for treating atopic dermatitis by adopting salvianolic acid B according to claim 3, characterized in that, The amount of xanthan gum used in steps C and E accounts for 70% and 30% of the total amount of xanthan gum, respectively.

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