Use of corydalis yanhusuo-angelica dahurica extract in preparation of Anti-atopic dermatitis drug

Abstract

The present invention aims to provide a use of a Corydalis yanhusuo-Angelica dahurica extract in the preparation of an anti-atopic dermatitis drug. The research result of the present invention shows that the Corydalis yanhusuo-Angelica dahurica extract can effectively treat atopic dermatitis, and the treatment effect of the Corydalis yanhusuo-Angelica dahurica extract is superior to the effect of the use of Corydalis yanhusuo and Angelica dahurica alone. An Angelica dahurica extract has almost no effect on atopic dermatitis when being used alone, but can obviously improve the treatment effect of a Corydalis yanhusuo extract when being used in combination with the Corydalis yanhusuo extract, and the administration dosages of Corydalis yanhusuo and Angelica dahurica in drug combination are reduced compared with those when used alone, indicating that the Corydalis yanhusuo extract and the Angelica dahurica extract achieve the effects of reducing toxicity and enhancing efficacy.

Description

Application of Corydalis yanhusuo-Angelica dahurica extract in the preparation of anti-atopic dermatitis drugs Technical Field

[0001] The invention belongs to the field of preparation of anti-atopic dermatitis drugs and relates to application of a Corydalis yanhusuo-Angelica dahurica extract in the preparation of anti-atopic dermatitis drugs. Background Art

[0002] The Yanhusuo-Angelica extract, composed of Yanhusuo and Angelica dahurica, has the effects of regulating qi, promoting blood circulation, and relieving pain. It is primarily used to treat pain symptoms caused by qi stagnation and blood stasis. The Yanhusuo extract has multiple pharmacological effects, including promoting blood circulation, vasodilation, anti-thrombotic effects, protection against myocardial ischemia and reperfusion injury, anti-arrhythmia, antihypertensive effects, myocardial protection, antioxidant effects, analgesic effects, sedative and hypnotic effects, anti-acetylcholinesterase effects, anti-epileptic effects, anti-drug dependence effects, and anti-tumor and anti-ulcer effects. Angelica dahurica has antipyretic, analgesic, and anti-tumor effects.

[0003] Atopic dermatitis (AD), also known as atopic eczema, formerly known as "atopic dermatitis" and "genetic allergic dermatitis", is a chronic, recurrent itchy skin disease. Patients often experience dry skin, itching and eczema-like rash.

[0004] Patients often have a family history of atopic diseases, such as asthma and allergic rhinitis. Studies have shown that if one parent has AD, the incidence in children can reach over 25% within three months of birth and over 50% within two years of birth. If both parents have a history of atopic disease, the incidence in their children can reach as high as 79%. Patients with atopic dermatitis exhibit immune abnormalities, manifested by elevated serum IgE levels and increased eosinophil counts in peripheral blood and tissues.

[0005] Atopic dermatitis may be caused by a breakdown in the skin barrier function, which can increase skin permeability and transepidermal water loss, leading to dry and flaky skin. Furthermore, allergens and pathogens can easily enter the body through the skin, thereby inducing or aggravating immunity and inflammation. Therefore, the treatment principle of atopic dermatitis is to restore the skin's normal barrier function. Currently, there is no definitive treatment, and glucocorticoids and antibiotics are commonly used in clinical practice. However, since long-term use of steroids can lead to adverse reactions such as skin wrinkling and water loss, there is no drug that can completely cure atopic dermatitis. Therefore, the development of new, safe and effective drugs for the treatment of atopic dermatitis is urgently needed.

[0006] Currently, there are no reports on the application of Corydalis yanhusuo-Angelica dahurica extract as an anti-atopic dermatitis drug. Technical issues

[0007] In order to overcome the above-mentioned shortcomings of the prior art, the object of the present invention is to provide a use of Corydalis yanhusuo-Angelica dahurica extract in the preparation of an anti-atopic dermatitis drug. Technical Solutions

[0008] The present invention is achieved through the following technical solutions:

[0009] Application of Corydalis yanhusuo-Angelica dahurica extract in the preparation of anti-atopic dermatitis drugs.

[0010] Preferably, the drug has the effect of inhibiting the release of skin itching mediators.

[0011] Preferably, the drug has the effect of inhibiting the release of inflammatory factors in the skin epidermis.

[0012] Preferably, the drug has the effect of inhibiting the production of skin scales.

[0013] Preferably, the drug has the effect of inhibiting damage to the epidermal barrier.

[0014] Preferably, the drug has the effect of inhibiting weight loss.

[0015] Preferably, the preparation method of the Corydalis yanhusuo-angelica dahurica extract is: taking Corydalis yanhusuo and angelica dahurica, crushing them, soaking them in ethanol solution, heating and refluxing, collecting the extract, filtering, and concentrating the filtrate into a thick paste.

[0016] A drug for treating atopic dermatitis, comprising a Corydalis yanhusuo-Angelica dahurica extract.

[0017] Preferably, the pharmaceutical dosage form is a gel, ointment, cream, powder, aqueous solution or lotion, and more preferably the dosage form is a gel.

[0018] Furthermore, the concentration of the Corydalis yanhusuo-Angelica dahurica extract in the medicine is 0.1-0.4 g / mL. Beneficial effects

[0019] The present invention has found that the extract of Corydalis yanhusuo and Angelica dahurica has an anti-atopic dermatitis effect and can significantly alleviate the symptoms of atopic dermatitis. The present invention constructs a mouse atopic dermatitis model and investigates the number of ear scratching, weight loss, epidermal barrier damage and ear thickening of the mice to evaluate the therapeutic effect of the drug on atopic dermatitis. The results show that the extract of Corydalis yanhusuo and Angelica dahurica can effectively treat atopic dermatitis, and the therapeutic effect of the extract of Corydalis yanhusuo and Angelica dahurica is better than the effect of using Corydalis yanhusuo and Angelica dahurica alone. Angelica dahurica extract has almost no effect on atopic dermatitis when used alone, but it can significantly improve the therapeutic effect of the extract of Corydalis yanhusuo when used in combination with the extract of Corydalis yanhusuo. The dosage of Corydalis yanhusuo and Angelica dahurica in the drug combination is lower than that when used alone, indicating that the extract of Corydalis yanhusuo and Angelica dahurica play a role in reducing toxicity and increasing effectiveness.

[0020] The invention uses the extract of Corydalis yanhusuo and Angelica dahurica to make a gel, which allows drugs to be better applied to the skin, promotes drug absorption, and improves drug efficacy. The gel made with the extract of Corydalis yanhusuo and Angelica dahurica as the main component has a better effect in treating atopic dermatitis. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] FIG1 is a graph showing the results of the inhibition of the Corydalis yanhusuo-Angelica dahurica extract on the number of times of scratching the ear skin of mice induced by calcipotriol;

[0022] FIG2 is a graph showing the results of the inhibition of Corydalis yanhusuo-Angelica dahurica extract on calcipotriol-induced weight loss in mice;

[0023] FIG3 shows the results of the inhibition of Corydalis yanhusuo-Angelica dahurica extract on calcipotriol-induced damage to the epidermal barrier of the mouse ears;

[0024] FIG4 shows the results of the inhibition of Corydalis yanhusuo-Angelica dahurica extract on calcipotriol-induced ear thickening in mice.

[0025] Figure 5 shows the results that the effect of Corydalis yanhusuo-Angelica dahurica extract in inhibiting mouse scratching is better than that of Angelica dahurica and Corydalis yanhusuo alone.

[0026] FIG6 shows the results that the effect of the Corydalis yanhusuo-Angelica dahurica extract gel on calcipotriol-induced ear thickening in mice is better than that of the Corydalis yanhusuo-Angelica dahurica extract. Modes for Carrying Out the Invention

[0027] In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the embodiments described 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 making creative efforts should fall within the scope of protection of the present invention.

[0028] Example 1 Preparation of Corydalis yanhusuo-Angelica dahurica Extract

[0029] Prepare 400 g each of vinegared Corydalis yanhusuo (purchased from Ningxia Mingde Chinese Medicine Pieces Co., Ltd.) and Angelica dahurica (purchased from Ningxia Mingde Chinese Medicine Pieces Co., Ltd.). Grind 166 g of Angelica dahurica into a fine powder. Grind the remaining Angelica dahurica and vinegared Corydalis yanhusuo into a coarse powder. Soak the mixture in three times the amount of 60% ethanol for 24 hours, heat under reflux for 3 hours, and collect the extract. Add two times the amount of 60% ethanol and heat under reflux for 2 hours. Collect the extract, combine the two extracts, filter, and concentrate the filtrate into a thick paste. The 2015 edition of the Chinese Pharmacopoeia includes a method for determining the content of Corydalis yanhusuo-Angelica extract. Using tetrahydropalmatine and imperatorin as indicator components, the Corydalis yanhusuo-Angelica extract was determined using high-performance liquid chromatography. The imperatorin content in the Corydalis yanhusuo-Angelica extract was 80 μg / mL, and the tetrahydropalmatine content in the Corydalis yanhusuo-Angelica extract was 60 μg / mL.

[0030] Example 2 Preparation of Corydalis yanhusuo-Angelica dahurica Extract Gel

[0031] 6.67 g of 30% poloxamer P407, 1 g of 45% poloxamer P188, and 2.33 g of H2O were mixed evenly to prepare a gel matrix. The Corydalis yanhusuo-Angelica dahurica extract and the gel matrix were mixed in a mass ratio of 1:9 to prepare a Corydalis yanhusuo-Angelica dahurica extract gel with a crude drug amount of 0.25 g / mL. The gel was centrifuged at 5000 r for 5 minutes to obtain a high-concentration Corydalis yanhusuo-Angelica dahurica extract gel.

[0032] The high-concentration gel of Corydalis yanhusuo and Angelica dahurica extract was mixed with the gel matrix in a mass ratio of 1:1 to obtain the low-concentration gel of Corydalis yanhusuo and Angelica dahurica extract. The high-concentration gel was mixed with the low-concentration gel in a mass ratio of 1:1 to obtain the medium-concentration gel of Corydalis yanhusuo and Angelica dahurica extract.

[0033] Example 3: Corydalis yanhusuo-Angelica dahurica extract gel inhibits calcipotriol-induced atopic dermatitis symptoms in mice

[0034] 1. Experimental Materials

[0035] Corydalis yanhusuo-angelica extract, calcipotriol (purchased from MCE), 6-8 week old female C57 mice (purchased from the Experimental Animal Center of Xi'an Jiaotong University)

[0036] 2. Experimental methods

[0037] Mice were divided into the NC group, the vehicle group, the positive control group, a low-concentration Corydalis yanhusuo-Angelica dahurica extract group (0.125 g / mL), a medium-concentration Corydalis yanhusuo-Angelica dahurica extract group (0.1875 g / mL), and a high-concentration Corydalis yanhusuo-Angelica dahurica extract group (0.25 g / mL). The NC group was administered an equal volume of anhydrous ethanol. For the vehicle group, calcipotriol (MC903) was dissolved in anhydrous ethanol and 20 μL was applied bilaterally to each ear of each mouse for 14 consecutive days. For the positive control group, calcipotriol was dissolved in anhydrous ethanol and 20 μL was applied bilaterally to each ear of each mouse for 14 consecutive days. Corticosteroids were also applied to the ears daily starting on day 8. For the low-concentration, medium-concentration, and high-concentration Corydalis-Angelica extract groups, 20 μL of calcipotriol dissolved in anhydrous ethanol was applied bilaterally to each ear of each mouse for 14 consecutive days. Starting on day 8, the Corydalis-Angelica extract in a gel matrix was applied daily to the ears. On day 14, the number of scratches within 10 minutes was counted for each group, and mice were sacrificed and ear tissues were collected.

[0038] 3. Experimental results

[0039] As shown in Figure 1, compared to the NC group, mice treated with calcipotriol scratched their ears significantly more frequently, indicating that calcipotriol application leads to elevated levels of itch mediators in the skin, leading to the development of itch symptoms characteristic of atopic dermatitis. This successfully established an atopic dermatitis model. Administration of the Corydalis yanhusuo-Angelica dahurica extract to mice with atopic dermatitis decreased scratching compared to the vehicle group, demonstrating that the Corydalis yanhusuo-Angelica dahurica extract effectively inhibits elevated levels of itch mediators in the skin. The efficacy of the Corydalis yanhusuo-Angelica dahurica extract at a concentration of 0.25 g / mL was comparable to that of the active drug.

[0040] As shown in Figure 2, compared with the NC group, mice treated with calcipotriol lost weight. Mice treated with the Corydalis yanhusuo-Angelica extract to the ears experienced less weight loss than the Vehicle group, indicating that the Corydalis yanhusuo-Angelica extract can effectively reduce weight loss. However, the use of the positive drug glucocorticoid increased weight loss, suggesting that the positive drug glucocorticoid is too toxic to mice. Compared with the positive drug, the Corydalis yanhusuo-Angelica extract did not cause weight loss in mice, indicating no toxic effects.

[0041] As can be seen from Figure 3, compared with the NC group, the mice that were applied with calcipotriol had damage to the epidermal barrier of the ear skin and an increase in scales due to increased scratching. The mice that were given the Corydalis Root-Angelica Extract had significantly less damage to the epidermal barrier than the Vehicle group, and the ear scales were significantly reduced, indicating that the Corydalis Root-Angelica Extract can effectively inhibit the damage to the epidermal barrier of the mouse skin caused by scratching. As the concentration of the Corydalis Root-Angelica Extract decreased, the inhibitory effect weakened. After the positive drug glucocorticoid was applied to the ears of mice, the damage to the epidermal barrier of the skin was inhibited, but the skin of the mouse ears wrinkled, resulting in adverse reactions; however, the application of the Corydalis Root-Angelica Extract did not cause ear wrinkling.

[0042] As shown in Figure 4, compared to the NC group, the ear thickness of mice treated with calcipotriol increased, indicating that calcipotriol application caused an increase in the levels of inflammatory factors in the skin epidermis. However, the ear thickness of mice treated with Corydalis yanhusuo-Angelica extract did not increase significantly, indicating that Corydalis yanhusuo-Angelica extract effectively inhibited the increase in the levels of inflammatory factors in the skin epidermis. As the concentration of Corydalis yanhusuo-Angelica extract decreased, the inhibitory effect of Corydalis yanhusuo-Angelica extract on the release of inflammatory factors weakened. Compared with the positive drug, the inhibitory effect of Corydalis yanhusuo-Angelica extract on inflammatory factors was similar.

[0043] As shown above, ear application of the Corydalis-Angelica extract to mice effectively inhibited scratching frequency, weight loss, and elevated levels of itch mediators and inflammatory factors in the skin epidermis, alleviating atopic dermatitis symptoms in mice. A 0.25g / mL concentration of Angelica dahurica extract significantly improved atopic dermatitis symptoms in mice, exhibiting less toxicity and superior efficacy to commonly used glucocorticoids.

[0044] Example 4 The efficacy of the Yanhusuo-Angelica extract gel in inhibiting calcipotriol-induced atopic dermatitis in mice is better than that of the single agent

[0045] 1. Experimental Materials

[0046] Corydalis yanhusuo-angelica extract, calcipotriol (purchased from MCE), 6-8 week old male C57 mice (purchased from the Experimental Animal Center of Xi'an Jiaotong University)

[0047] 2. Experimental methods

[0048] Mice were divided into the NC group, vehicle group, positive control group, Angelica dahurica extract group, Corydalis yanhusuo extract group, and Corydalis yanhusuo-Angelica extract group. Corydalis yanhusuo-Angelica extract, Angelica dahurica extract, and Corydalis yanhusuo extract-Angelica extract groups were prepared using a gel matrix at 0.25 g / mL. For the vehicle group, 20 μL of calcipotriol (MC903) dissolved in ethanol was applied bilaterally to each ear of each mouse for 17 consecutive days. For the Angelica dahurica extract, Corydalis yanhusuo extract, and Corydalis yanhusuo-Angelica extract groups, 20 μL of calcipotriol dissolved in ethanol was applied bilaterally to each ear of each mouse for 17 consecutive days, with daily ear application starting on day 11. On day 14, the number of scratches within 10 minutes was counted for each group, and the mice were sacrificed and ear tissues were collected.

[0049] 3. Experimental results

[0050] The results are shown in Figure 5. As can be seen from Figure 5, application of Corydalis-Angelica extract and Corydalis extract to the mouse ears effectively inhibited ear scratching and alleviated atopic dermatitis symptoms in mice. However, Angelica extract not only failed to inhibit ear scratching, but also tended to increase it. Application of 0.25g / mL of Corydalis-Angelica extract significantly inhibited atopic dermatitis symptoms, demonstrating a therapeutic effect superior to that of Angelica extract or Corydalis extract alone. This suggests that Angelica extract alone has no effect on atopic dermatitis, but when used in combination with Corydalis extract, it can enhance the therapeutic efficacy of Corydalis extract.

[0051] The dosage of Corydalis yanhusuo and Angelica dahurica in the Corydalis yanhusuo-Angelica dahurica extract is lower than that of Angelica dahurica extract and Corydalis yanhusuo extract used alone, indicating that Corydalis yanhusuo and Angelica dahurica have a synergistic effect.

[0052] Example 5 The effect of the Yanhusuo-Angelica extract gel on inhibiting the increase of ear thickness in mice is better than that of the Yanhusuo-Angelica extract

[0053] 1. Experimental Materials

[0054] Corydalis yanhusuo-angelica dahurica extract, calcipotriol (purchased from MCE Company), and 6-8 week old male C57 mice (purchased from the Experimental Animal Center of Xi'an Jiaotong University).

[0055] 2. Experimental methods

[0056] Mice were divided into the NC group, vehicle group, positive control group, Corydalis yanhusuo-Angelica dahurica extract gel group, and Corydalis yanhusuo-Angelica dahurica extract group. A 0.25 g / mL Corydalis yanhusuo-Angelica dahurica extract gel was prepared using a gel matrix. For the vehicle group, 20 μL of calcipotriol (MC903) dissolved in ethanol was applied bilaterally to each ear of each mouse for 17 consecutive days. For the Corydalis yanhusuo-Angelica dahurica extract gel and Corydalis yanhusuo-Angelica dahurica extract groups, 20 μL of calcipotriol dissolved in ethanol was applied bilaterally to each ear of each mouse for 17 consecutive days, with daily ear application starting on day 11. On day 14, the number of scratches within 10 minutes was counted for each group, and mice were sacrificed and ear tissues were collected.

[0057] 3. Experimental results

[0058] The results are shown in Figure 6. As can be seen from Figure 6, applying the Corydalis yanhusuo-Angelica extract and the Corydalis yanhusuo-Angelica extract gel to the mice's ears can effectively inhibit the increase in ear thickness caused by calcipotriol and alleviate the symptoms of atopic dermatitis in mice, but the Corydalis yanhusuo-Angelica extract gel group has a better effect than the Corydalis yanhusuo-Angelica extract group.

[0059] The technical idea of ​​the present invention is to illustrate the technical idea of ​​the present invention, and the protection scope of the present invention cannot be limited by this. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. Application of Corydalis yanhusuo-Angelica dahurica extract in the preparation of anti-atopic dermatitis drugs.

2. The use according to claim 1, characterized in that: The drug has the effect of inhibiting the release of skin itching mediators.

3. The use according to claim 1, characterized in that: The medicine has the effect of inhibiting the release of skin epidermal inflammatory factors.

4. The use according to claim 1, characterized in that: The drug has the effect of inhibiting the generation of skin scales.

5. The use according to claim 1, characterized in that: The drug has the effect of inhibiting the damage of the epidermal barrier.

6. The use according to claim 1, characterized in that: The drug has an effect of inhibiting weight loss.

7. The use according to claim 1, characterized in that: The preparation method of the Corydalis yanhusuo-angelica dahurica extract is as follows: taking Corydalis yanhusuo and angelica dahurica, crushing them, soaking them in ethanol solution, heating and refluxing, collecting the extract, filtering, and concentrating the filtrate into a thick paste.

8. A drug for treating atopic dermatitis, characterized in that: The medicine comprises Corydalis yanhusuo-Angelica dahurica extract.

9. The anti-atopic dermatitis drug according to claim 8, characterized in that: The dosage form of the medicine is gel, ointment, cream, powder, aqueous solution or lotion.

10. The anti-atopic dermatitis drug according to claim 9, characterized in that: The concentration of the Corydalis yanhusuo-Angelica dahurica extract in the medicine is 0.1-0.4 g / mL.

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