Application of Corydalis Rhizoma - Angelicae Dahuricae Radix extract in preparing drug for treating atopic dermatitis

Abstract

The object of the present invention is to provide the application of Corydalis yanhusuo - Angelica dahurica extract in the preparation of drugs for treating atopic dermatitis. The research results of the present invention show that Corydalis yanhusuo - Angelica dahurica extract can effectively treat atopic dermatitis, and the treatment effect of Corydalis yanhusuo - Angelica dahurica extract is better than that of Corydalis yanhusuo and Angelica dahurica used alone. The Angelica dahurica extract alone has almost no effect on atopic dermatitis, but when combined with the Corydalis yanhusuo extract, it can significantly improve the treatment effect of the Corydalis yanhusuo extract, and the dosage of Corydalis yanhusuo and Angelica dahurica in the drug combination is lower than that used alone, indicating that the Corydalis yanhusuo extract and the Angelica dahurica extract play a role in reducing toxicity and enhancing efficacy.

Description

Technical Field

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

[0002] The Corydalis yanhusuo-Angelica dahurica extract is composed of Corydalis yanhusuo and Angelica dahurica, and has the effects of regulating qi, activating blood circulation and relieving pain, and is mainly used for treating related pain diseases caused by qi stagnation and blood stasis. In the formula, Corydalis yanhusuo has various pharmacological effects such as promoting blood circulation, dilating blood vessels, anti-thrombosis, anti-myocardial ischemia and reperfusion injury, anti-arrhythmia, lowering blood pressure, protecting myocardium, antioxidation, analgesia, sedation and hypnosis, anti-acetylcholinesterase, anti-epilepsy, anti-drug dependence, anti-tumor and anti-ulcer. Angelica dahurica has effects such as antipyretic analgesia and anti-tumor.

[0003] Atopic dermatitis (AD), also known as atopic eczema, was formerly known as "atopic dermatitis" and "hereditary allergic dermatitis", is a chronic recurrent pruritic skin disease, and patients often show dry skin, itching and eczema-like rashes.

[0004] Patients usually have a family history of atopic diseases, such as asthma and allergic rhinitis. Studies have shown that if one parent has AD, the incidence rate within 3 months after the birth of the child can reach more than 25%, and the incidence rate within 2 years can reach more than 50%; if both parents have a history of atopic diseases, the incidence rate of their children is as high as 79%. Patients with atopic dermatitis have immune abnormalities, manifested as increased serum IgE levels, elevated eosinophils in peripheral blood and tissues, etc.

[0005] The inducement of atopic dermatitis may be the destruction of the skin barrier function. The destruction of the skin barrier function can cause increased skin permeability and increased transepidermal water loss, resulting in dry skin, desquamation, and allergens and pathogens are easily introduced into the human body through the skin, thus inducing or aggravating immunity and inflammation. Therefore, the treatment principle of atopic dermatitis is to restore the normal barrier function of the skin. At present, there is no exact treatment method, and glucocorticoids and antibiotics are commonly used clinically. However, due to the long-term use of hormonal drugs, adverse reactions such as skin shrinkage and water loss will occur, and there is no drug that can completely cure specific dermatitis, and there is an urgent need to develop new safe and effective drugs for treating specific dermatitis.

[0006] Currently, there is no relevant application report on the Corydalis yanhusuo-Angelica dahurica extract as an anti-specific dermatitis drug. Summary of the Invention

[0007] In order to overcome the above-mentioned disadvantages of the prior art, the purpose of the present invention is to provide the application of Corydalis yanhusuo-Angelica dahurica extract in the preparation of anti-atopic dermatitis drugs.

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

[0009] Application of Corydalis Rhizoma - Angelicae Dahuricae Radix extract in preparing drug for treating atopic dermatitis.

[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 skin epidermal inflammatory factors.

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

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

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

[0015] Preferably, the preparation method of the Corydalis Rhizoma - Angelicae Dahuricae Radix extract is as follows: take Corydalis Rhizoma and Angelicae Dahuricae Radix, crush them, soak them with ethanol solution, heat under reflux, collect the extract, filter, and concentrate the filtrate into a thick paste.

[0016] A drug for treating atopic dermatitis, the drug contains Corydalis Rhizoma - Angelicae Dahuricae Radix extract.

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

[0018] Furthermore, the concentration of Corydalis Rhizoma - Angelicae Dahuricae Radix extract in the drug is 0.1 - 0.4 g / mL.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] The present invention discovers through research that the Corydalis Rhizoma - Angelicae Dahuricae Radix extract has the effect of treating atopic dermatitis and can significantly relieve the symptoms of atopic dermatitis. The present invention constructs a mouse atopic dermatitis model, examines the scratching times of the mouse ears, the degree of weight loss, epidermal barrier damage and ear thickening to evaluate the therapeutic effect of the drug on atopic dermatitis. The results show that the Corydalis Rhizoma - Angelicae Dahuricae Radix extract can effectively treat atopic dermatitis, and the therapeutic effect of the Corydalis Rhizoma - Angelicae Dahuricae Radix extract is better than that of using Corydalis Rhizoma and Angelicae Dahuricae Radix alone. Using Angelicae Dahuricae Radix extract alone has almost no effect on atopic dermatitis, but when combined with Corydalis Rhizoma extract, it can significantly improve the therapeutic effect of Corydalis Rhizoma extract, and the dosage of Corydalis Rhizoma and Angelicae Dahuricae Radix in the drug combination is lower than that when used alone, indicating that there is a synergistic effect between Corydalis Rhizoma extract and Angelicae Dahuricae Radix extract.

[0021] The present invention makes the Corydalis Rhizoma - Angelicae Dahuricae Radix extract into a gel, which can make the drug better applied to the skin, promote drug absorption and improve the drug effect. The gel preparation mainly composed of Corydalis Rhizoma - Angelicae Dahuricae Radix extract has a better effect on treating atopic dermatitis. Description of the Drawings

[0022] Figure 1 It is a graph showing the inhibitory effect of Corydalis yanhusuo - Angelica dahurica extract on the number of times of scratching the ear skin of mice induced by calcipotriol;

[0023] Figure 2 It is a graph showing the inhibitory effect of Corydalis yanhusuo - Angelica dahurica extract on the weight loss of mice induced by calcipotriol;

[0024] Figure 3 It is a graph showing the inhibitory effect of Corydalis yanhusuo - Angelica dahurica extract on the damage of the ear epidermal barrier of mice induced by calcipotriol;

[0025] Figure 4 It is a graph showing the inhibitory effect of Corydalis yanhusuo - Angelica dahurica extract on the ear thickening of mice induced by calcipotriol.

[0026] Figure 5 It is a graph showing that the inhibitory effect of Corydalis yanhusuo - Angelica dahurica extract on mouse scratching is better than that of Angelica dahurica and Corydalis yanhusuo used alone.

[0027] Figure 6 It is a graph showing that the effect of Corydalis yanhusuo - Angelica dahurica extract gel on the ear thickening of mice induced by calcipotriol is better than that of Corydalis yanhusuo - Angelica dahurica extract. Detailed Embodiments

[0028] In order to enable those skilled in the art to better understand the solution 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 accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0029] Example 1 Preparation of Corydalis yanhusuo - Angelica dahurica Extract

[0030] Prepare 400 g each of Corydalis yanhusuo processed with vinegar (purchased from Ningxia Mingde Chinese Herbal Medicine Pieces Co., Ltd.) and Angelica dahurica (purchased from Ningxia Mingde Chinese Herbal Medicine Pieces Co., Ltd.). Take 166 g of Angelica dahurica and pulverize it into fine powder. Pulverize the remaining Angelica dahurica and Corydalis yanhusuo processed with vinegar into coarse powder, soak it in three times the amount of 60% ethanol for 24 hours, heat and reflux for 3 hours, collect the extract, then add twice the amount of 60% ethanol and heat and 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 the content determination method for Corydalis yanhusuo - Angelica dahurica extract. Using tetrahydropalmatine and imperatorin as the index components, the Corydalis yanhusuo - Angelica dahurica extract is determined by high - performance liquid chromatography. The content of imperatorin in the Corydalis yanhusuo - Angelica dahurica extract is 80 ug / mL, and the content of tetrahydropalmatine in the Corydalis yanhusuo - Angelica dahurica extract is 60 ug / mL.

[0031] Example 2 Preparation of Corydalis Rhizoma - Angelicae Dahuricae Radix Extract Gel

[0032] Mix 6.67 g of 30% poloxamer P407, 1 g of 45% poloxamer P188 and 2.33 g of H2O evenly to prepare a gel matrix. Mix the Corydalis Rhizoma - Angelicae Dahuricae Radix extract with the gel matrix according to a mass ratio of 1:9 to prepare a Corydalis Rhizoma - Angelicae Dahuricae Radix extract gel with a crude drug content of 0.25 g / mL. Centrifuge at 5000 r for 5 minutes to obtain a high - concentration Corydalis Rhizoma - Angelicae Dahuricae Radix extract gel.

[0033] Mix the high - concentration Corydalis Rhizoma - Angelicae Dahuricae Radix extract gel with the gel matrix according to a mass ratio of 1:1 to obtain a low - concentration Corydalis Rhizoma - Angelicae Dahuricae Radix extract gel. Mix the high - concentration gel and the low - concentration gel according to a mass ratio of 1:1 to obtain a medium - concentration Corydalis Rhizoma - Angelicae Dahuricae Radix extract gel.

[0034] Example 3 Inhibition of Atopic Dermatitis Symptoms in Mice Induced by Calcipotriol by Corydalis Rhizoma - Angelicae Dahuricae Radix Extract Gel

[0035] 1. Experimental Materials

[0036] Corydalis Rhizoma - Angelicae Dahuricae Radix extract, calcipotriol (purchased from MCE Company), female C57 mice aged 6 - 8 weeks (purchased from the Experimental Animal Center of Xi'an Jiaotong University)

[0037] 2. Experimental Methods

[0038] Divide the mice into NC group, Vehicle group, positive control group, low - concentration Corydalis Rhizoma - Angelicae Dahuricae Radix extract group (0.125 g / mL), medium - concentration Corydalis Rhizoma - Angelicae Dahuricae Radix extract group (0.1875 g / mL concentration) and high - concentration Corydalis Rhizoma - Angelicae Dahuricae Radix extract group (0.25 g / mL). The NC group is given an equal volume of absolute ethanol. For the Vehicle group, calcipotriol (MC903) is dissolved in absolute ethanol and then 20 μL is applied bilaterally to each ear of each mouse for 14 consecutive days. For the positive control group, calcipotriol is dissolved in absolute ethanol, 20 μL is applied bilaterally to each ear of each mouse for 14 consecutive days, and glucocorticoid is applied to the ear from the 8th day. For the low - concentration Corydalis Rhizoma - Angelicae Dahuricae Radix extract group, medium - concentration Corydalis Rhizoma - Angelicae Dahuricae Radix extract group and high - concentration Corydalis Rhizoma - Angelicae Dahuricae Radix extract group, calcipotriol is dissolved in absolute ethanol, 20 μL is applied bilaterally to each ear of each mouse for 14 consecutive days, and the Corydalis Rhizoma - Angelicae Dahuricae Radix extract prepared with the gel matrix is applied to the ear from the 8th day. On the 14th day of each group, count the scratching times within 10 min, sacrifice the mice, and take ear tissues.

[0039] 3. Experimental Results

[0040] FromFigure 1 It can be seen that, compared with the NC group, the number of ear scratches of the mice smeared with calcipotriol increased significantly, indicating that the content of skin itching mediators increased after smearing calcipotriol, and the itching symptoms of atopic dermatitis appeared, successfully establishing an atopic dermatitis model. After giving the extract of Corydalis yanhusuo - Angelica dahurica to the mice with atopic dermatitis, compared with the Vehicle group, the number of scratches of the mice decreased, indicating that the extract of Corydalis yanhusuo - Angelica dahurica can effectively inhibit the increase in the content of skin itching mediators. The effect of the extract of Corydalis yanhusuo - Angelica dahurica at a concentration of 0.25 g / mL is equivalent to that of the positive drug.

[0041] From Figure 2 It can be seen that, compared with the NC group, the body weight of the mice smeared with calcipotriol decreased. The degree of body weight decrease of the mice smeared with the extract of Corydalis yanhusuo - Angelica dahurica on the ear was less than that of the Vehicle group, indicating that the extract of Corydalis yanhusuo - Angelica dahurica can effectively reduce the degree of body weight decrease. However, the degree of body weight decrease with the positive drug glucocorticoid increased, indicating that the positive drug glucocorticoid has too much toxicity to the mice. Compared with the positive drug, the extract of Corydalis yanhusuo - Angelica dahurica did not cause a decrease in the body weight of the mice and no toxic effects occurred.

[0042] From Figure 3 It can be seen that, compared with the NC group, the ear skin epidermal barrier of the mice smeared with calcipotriol was damaged due to the increase in the number of scratches, and the scales increased. The degree of epidermal barrier damage of the mice smeared with the extract of Corydalis yanhusuo - Angelica dahurica on the ear was significantly less than that of the Vehicle group, and the ear scales were significantly reduced, indicating that the extract of Corydalis yanhusuo - Angelica dahurica can effectively inhibit the damage of the mouse skin epidermal barrier caused by scratching. As the concentration of the extract of Corydalis yanhusuo - Angelica dahurica decreased, the inhibitory effect weakened. After giving the positive drug glucocorticoid to the mice by ear application, the damage of the skin epidermal barrier was inhibited, but the ear skin of the mice shrank, resulting in adverse reactions; while smearing the extract of Corydalis yanhusuo - Angelica dahurica did not cause ear shrinkage.

[0043] From Figure 4 It can be seen that, compared with the NC group, the ear thickness of the mice smeared with calcipotriol increased, indicating that the content of skin epidermal inflammatory factors increased after smearing calcipotriol. The increase in ear thickness of the mice smeared with the extract of Corydalis yanhusuo - Angelica dahurica on the ear was not obvious, which means that smearing the extract of Corydalis yanhusuo - Angelica dahurica on the mice can effectively inhibit the increase in the content of skin epidermal inflammatory factors. As the concentration of the extract of Corydalis yanhusuo - Angelica dahurica decreased, the inhibitory effect of the extract of Corydalis yanhusuo - Angelica dahurica on the release of inflammatory factors weakened. Compared with the positive drug, the effect of the extract of Corydalis yanhusuo - Angelica dahurica in inhibiting inflammatory factors was similar.

[0044] As can be seen from the above, applying Corydalis yanhusuo - Angelica dahurica extract to the ears of mice can effectively inhibit the increase in the number of scratching times, the degree of weight loss, the content of skin itching mediators, and the content of skin epidermal inflammatory factors, and relieve the symptoms of atopic dermatitis in mice. The extract of Angelica dahurica - Corydalis yanhusuo at a concentration of 0.25 g / mL can significantly improve the symptoms of atopic dermatitis in mice, and has less toxicity and better efficacy than the commonly used glucocorticoid drugs in clinical practice.

[0045] Example 4 The efficacy of the gel of Corydalis yanhusuo - Angelica dahurica extract in inhibiting atopic dermatitis induced by calcipotriol in mice is better than that of using it alone

[0046] 1. Experimental materials

[0047] Corydalis yanhusuo - Angelica dahurica extract, calcipotriol (purchased from MCE Company), male C57 mice aged 6 - 8 weeks (purchased from the Experimental Animal Center of Xi'an Jiaotong University)

[0048] 2. Experimental methods

[0049] The mice were divided into NC group, Vehicle group, positive control group, Angelica dahurica extract group, Corydalis yanhusuo extract group, and Corydalis yanhusuo - Angelica dahurica extract group. Prepare 0.25 g / mL Corydalis yanhusuo - Angelica dahurica extract, 0.25 g / mL Angelica dahurica extract, and 0.25 g / mL Corydalis yanhusuo extract with a gel matrix. For the Vehicle group, calcipotriol (MC903) was dissolved in ethanol, and 20 μL was applied to both sides of each ear of each mouse for 17 consecutive days. For the Angelica dahurica extract group, Corydalis yanhusuo extract group, and Corydalis yanhusuo - Angelica dahurica extract group, calcipotriol was dissolved in ethanol, and 20 μL was applied to both sides of each ear of each mouse for 17 consecutive days, and drug administration was applied to the ears every day starting from the 11th day. On the 14th day of each group, the number of scratching times within 10 min was counted, and the mice were sacrificed and ear tissues were taken.

[0050] 3. Experimental results

[0051] The results are shown in Figure 5 . As can be seen from Figure 5 , applying Corydalis yanhusuo - Angelica dahurica extract and Corydalis yanhusuo extract to the ears of mice can effectively inhibit the number of times of scratching the ear skin and relieve the symptoms of atopic dermatitis in mice. However, the Angelica dahurica extract not only fails to inhibit the number of times of scratching the ear skin but also has a tendency to increase the number of scratching times. The application of 0.25 g / mL Corydalis yanhusuo - Angelica dahurica extract significantly inhibits the symptoms of atopic dermatitis, and its therapeutic effect is better than that of using Angelica dahurica extract and Corydalis yanhusuo extract alone, indicating that Angelica dahurica extract alone has no effect on atopic dermatitis, but can increase the therapeutic effect of Corydalis yanhusuo extract when used in combination with it.

[0052] The administration doses of Corydalis yanhusuo and Angelica dahurica in the Corydalis yanhusuo - Angelica dahurica extract are lower than those when Angelica dahurica extract and Corydalis yanhusuo extract are used alone, indicating that Corydalis yanhusuo and Angelica dahurica play a synergistic effect.

[0053] Example 5: The effect of the Corydalis yanhusuo - Angelica dahurica extract gel in inhibiting the increase in ear thickness of mice is better than that of the Corydalis yanhusuo - Angelica dahurica extract

[0054] 1. Experimental materials

[0055] Corydalis yanhusuo - Angelica dahurica extract, calcipotriol (purchased from MCE Company), male C57 mice aged 6 - 8 weeks (purchased from the Experimental Animal Center of Xi'an Jiaotong University).

[0056] 2. Experimental methods

[0057] The mice were divided into 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 was prepared with a gel matrix to obtain the Corydalis yanhusuo - Angelica dahurica extract gel. For the Vehicle group, calcipotriol (MC903) was dissolved in ethanol, and 20 μL was applied bilaterally to each ear of each mouse for 17 consecutive days. For the Corydalis yanhusuo - Angelica dahurica extract gel group and the Corydalis yanhusuo - Angelica dahurica extract group, calcipotriol was dissolved in ethanol, and 20 μL was applied bilaterally to each ear of each mouse for 17 consecutive days, and topical administration to the ears was carried out every day starting from the 11th day. On the 14th day of each group, the scratching times within 10 min were counted, and the mice were sacrificed and ear tissues were taken.

[0058] 3. Experimental results

[0059] The results are shown in Figure 6 . It can be seen from Figure 6 that topical application of the Corydalis yanhusuo - Angelica dahurica extract and the Corydalis yanhusuo - Angelica dahurica extract gel to the ears of mice can effectively inhibit the increase in ear thickness caused by calcipotriol and relieve the symptoms of atopic dermatitis in mice, but the effect of the Corydalis yanhusuo - Angelica dahurica extract gel group is better than that of the Corydalis yanhusuo - Angelica dahurica extract group.

[0060] To illustrate the technical idea of the present invention, the protection scope of the present invention cannot be limited thereby. Any modification made on the basis of the technical solution according to the technical idea proposed by the present invention falls within the protection scope of the claims of the present invention.

Claims

1. The application of Corydalis yanhusuo - Angelica dahurica extract in the preparation of an external drug for treating atopic dermatitis, characterized in that, The preparation method of the Corydalis Rhizoma - Angelicae Dahuricae Radix extract is as follows: Take Corydalis Rhizoma and Angelicae Dahuricae Radix in a mass ratio of 1:1, crush them, soak them in a 60% ethanol solution, heat under reflux, collect the extract, filter, and concentrate the filtrate into a thick paste; the active ingredient of the drug is made from the Corydalis Rhizoma - Angelicae Dahuricae Radix extract, and the concentration of the Corydalis Rhizoma - Angelicae Dahuricae Radix extract in the drug is 0.1 - 0.4 g / mL.

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

3. The application according to claim 1, wherein The drug has the effect of inhibiting the release of skin epidermal inflammatory factors.

4. The application according to claim 1, wherein The drug has the effect of inhibiting the production of skin scales.

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

6. The application according to claim 1, wherein The drug has the effect of inhibiting weight loss.

7. The application according to claim 1, characterized in that, The dosage form of the drug is gel, ointment or lotion.

8. The application according to claim 1, wherein The dosage form of the drug is cream or aqueous solution.

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