Externally applied medicine for treating chronic inflammatory dermatosis as well as preparation method and application of externally applied medicine

Abstract

The invention belongs to the field of traditional Chinese medicines, and discloses an external medicine for treating chronic inflammatory dermatosis, which is mainly prepared from the following raw material components in parts by weight: 10-100 parts of cortex dictamni, 10-50 parts of fructus psoraleae, 10-100 parts of golden larch bark and 10-100 parts of moutan bark. The preparation method comprises the following steps: weighing the cortex dictamni, the fructus psoraleae, the cortex pseudolaricis and the cortex moutan according to a formula ratio, adding water, decocting twice, and combining filtrates; and concentrating the filtrate under reduced pressure to obtain clear paste, namely the external medicine for treating the chronic inflammatory dermatosis. The invention also discloses an application of the external medicine in preparation of medicines for treating chronic inflammatory dermatosis. The external medicine for treating the chronic inflammatory dermatosis does not use cortex fraxini, so that the toxic and side effects of the medicine can be remarkably reduced, and the external medicine is suitable for a wide range of people and also has a relatively good treatment effect on the chronic inflammatory dermatosis.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine, and in particular relates to an external medicine for treating chronic inflammatory skin diseases and a preparation method and application thereof. Background Art

[0002] Chronic inflammatory skin diseases are stubborn and difficult to treat, and they recur repeatedly, causing physical and mental damage to patients. Common chronic inflammatory skin diseases mainly include psoriasis and atopic dermatitis. Psoriasis is characterized by papules and erythema on the skin, covered with white scales on the surface. Psoriasis, known as dry psoriasis and white scabies in traditional Chinese medicine, is extremely difficult to treat clinically because of its repeated attacks and lingering difficulty in healing. Most ancient doctors believed that psoriasis was related to exogenous evil spirits such as wind, heat, and dampness. "Treatise on the Causes and Symptoms of Various Diseases" states that "dry psoriasis...are all caused by wind and rheumatism evil spirits, which invade the skin, and are combined with cold and dampness, and fight against blood and qi." "The Golden Mirror of the Medical Ancestral · Essentials of the Heart of Surgery" says that "white scabies...are caused by wind evil invading the skin, and also by blood dryness that makes it difficult to nourish the outside." "The Standards of Diagnosis and Treatment" states that "there is also white ringworm... This is caused by the weakness of the skin and the wind, which makes the blood stagnate and unable to nourish the muscles." After a long time, it will turn into insect evil and poison evil, such as "The Golden Mirror of the Medical Ancestral · Essentials of Surgery": "This syndrome is always caused by wind, heat and dampness, which invade the skin. If the wind is strong for a long time, it will turn into insects, so the itching will never stop." And so on. In short, the external causes of psoriasis are mostly caused by wind, cold, dampness, heat, dryness and poison, which invade the skin; the internal causes are mostly caused by endowed blood heat, unclean diet, emotional injury, etc. Atopic dermatitis is characterized by dry skin, chronic eczematoid dermatitis and severe itching. For these two diseases, mild patients are mainly treated with topical drugs, and moderate and severe patients need to be combined with topical drugs to improve the efficacy, shorten the course of the disease, and reduce adverse reactions. However, the topical drugs approved for the treatment of chronic inflammatory skin diseases are limited, and long-term use is prone to drug resistance and reduced patient compliance. However, the market currently lacks traditional Chinese medicine topical preparations with definite efficacy and high safety for the treatment of chronic inflammatory skin diseases. Therefore, there is an urgent need to develop safe, effective, and mechanism-defined external Chinese medicine preparations. Summary of the invention

[0003] The technical problem to be solved by the present invention is to overcome the deficiencies and defects mentioned in the above background technology and provide an external medicine for treating chronic inflammatory skin diseases and a preparation method and application thereof.

[0004] In order to solve the above technical problems, the technical solution proposed by the present invention is: An external-use medicine for treating chronic inflammatory skin diseases, mainly composed of the following raw material components in parts by weight: 10-100 parts of Dictamni Cortex, 10-50 parts of Psoralea corylifolia, 10-100 parts of Cnidium monnieri Cortex, and 10-100 parts of Paeonia suffruticosa Cortex.

[0005] The above-mentioned external-use medicine for treating chronic inflammatory skin diseases is preferably made of the following raw material components in parts by weight: Dictamnus dasycarpus Turcz. 50 parts, Psoralea corylifolia L. 30 parts, Pseudolarix amabilis (Nelson) Rehd. 50 parts, Paeonia suffruticosa Andr. 50 parts.

[0006] The above-mentioned external medicine for treating chronic inflammatory skin diseases, preferably, the dosage form of the external medicine includes lotion, ointment, cream, gel, tincture, application, powder, lotion, spirit, oil, paste, plaster, film-forming agent or aerosol.

[0007] Based on a general inventive concept, the present invention also provides a preparation method of the above-mentioned external medicine for treating chronic inflammatory skin diseases, including the following steps: Weigh Dictamnus dasycarpus Turcz., Psoralea corylifolia L., Pseudolarix amabilis (Nelson) Rehd., and Paeonia suffruticosa Andr. according to the formula ratio, decoct twice with water, and combine the filtrates; then concentrate the filtrates under reduced pressure to clear paste, which is the external medicine for treating chronic inflammatory skin diseases.

[0008] For the above-mentioned preparation method, preferably, let the clear paste stand, take the supernatant, add sodium benzoate and boil, add purified water to make up the volume, stir well, and fill into containers.

[0009] For the above-mentioned preparation method, preferably, add 10 - 15 times the amount of water for the first decoction, decoct for 1 - 2 hours, and filter; add 5 - 10 times the amount of water for the second decoction, decoct for 0.5 - 1.5 hours.

[0010] For the above-mentioned preparation method, preferably, the reduced pressure concentration is carried out at 65 - 75 °C and -0.06 ~ -0.08 MPa.

[0011] For the above-mentioned preparation method, preferably, the relative density of the clear paste is 1.02 - 1.06, and the relative density refers to the density relative to water.

[0012] Based on a general inventive concept, the present invention also provides an application of the above-mentioned external medicine for treating chronic inflammatory skin diseases in the preparation of drugs for treating chronic inflammatory skin diseases.

[0013] Dictamnus dasycarpus Turcz. is bitter and cold. It acts on the spleen, stomach, and bladder meridians. "Yaoxing Lun" states about Dictamnus dasycarpus Turcz.: "Treat all kinds of heat-toxic winds, evil winds, wind sores, scabies and tinea with red and rotten...". "Compendium of Materia Medica" says it is "the essential medicine for various yellow wind arthralgia". "Bencao Yuanshi" states: "Treat all kinds of scabies, evil winds, scabies and tinea, syphilis, and various sores with heat-toxicity." Dictamnus dasycarpus Turcz. has the effects of clearing heat and detoxifying, and drying dampness and relieving itching. It is widely used in eczema and dermatitis caused by damp-heat, skin ulceration, purulent discharge, skin itching and other symptoms. Aiming at the external pathogenic factors of wind-cold-damp-heat-dry-toxicity in chronic inflammatory skin diseases, Dictamnus dasycarpus Turcz. is set as the monarch drug in this formula.

[0014] Pseudolarix bark is pungent, dispersing, warm, dry and toxic, and can only be used externally. It is good at expelling wind, drying dampness and relieving itching, and has good effects of killing insects and treating tinea, and removing dampness and relieving itching. Psoralea fruit is pungent, bitter and warm, and has the effects of tonifying the kidney and securing essence, reducing urination and arresting leucorrhea, warming the spleen and stopping diarrhea, and securing the thoroughfare and arresting abortion. In recent years, it has been found that the external use of the extract of Psoralea fruit has a good therapeutic effect on skin diseases including psoriasis. Therefore, Pseudolarix bark and Psoralea fruit are selected as assistant drugs in this formula, and their external use helps the monarch drug to achieve the effects of expelling wind and relieving itching, and drying dampness and removing dandruff.

[0015] Regarding Cortex Moutan, "Compendium of Materia Medica" records that it "harmonizes blood, generates blood,... treats fire latent in blood and removes vexation and heat", summarizing the effects of Cortex Moutan in clearing heat and cooling blood, promoting blood circulation and removing stasis, and clearing deficiency heat. In addition, "Japanese Pharmacopoeia of Materia Medica" records that Cortex Moutan "makes the complexion pleasing", indicating that Cortex Moutan is also a traditional Chinese medicine with beauty effects and is also used in the treatment of skin diseases. Using Cortex Moutan as an adjuvant drug can lead all the drugs into the blood aspect, play its role in clearing heat and cooling blood, and promoting blood circulation and removing stasis, so as to treat the blood heat pathogenesis of psoriasis.

[0016] The combination of these four drugs has the effects of dispelling wind-cold, removing damp-heat, promoting blood circulation and detoxifying, and removing dandruff.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: The present invention is an improvement based on the applicant's previous patent (ZL201811121114.6), without using Cortex Fraxini, and the improved traditional Chinese medicine has the same curative effect in the treatment of chronic inflammatory skin diseases, can effectively improve the erythema, scales and thickness of mouse dermatitis, and the pathology shows that there is no significant difference in the improvement of mouse epidermal thickness between the improved formula and the previous patent. Therefore, compared with the formula of the previous patent, the present invention has the same curative effect in the treatment of chronic inflammatory skin diseases, and due to the reduction in the use of Cortex Fraxini, not only the drug cost is reduced, but also other adverse reactions caused by the long-term use of Cortex Fraxini are avoided. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 It is to compare the improvement degree of Example 1 and Comparative Example 1 on imiquimod-induced psoriatic dermatitis.

[0019] Figure 2 It is to compare the improvement degree of Example 1 and Comparative Example 1 on the epidermal thickness of psoriatic dermatitis from the pathological manifestations. DETAILED DESCRIPTION OF THE INVENTION

[0020] For the convenience of understanding the present invention, the following will describe the present invention more comprehensively and meticulously in combination with the accompanying drawings of the specification and preferred embodiments, but the protection scope of the present invention is not limited to the following specific embodiments.

[0021] Unless otherwise defined, all professional terms used hereinafter have the same meaning as commonly understood by those skilled in the art. The professional terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the protection scope of the present invention.

[0022] Unless otherwise specified, various raw materials, reagents, instruments, and equipment used in the present invention can be obtained through market purchases or prepared by existing methods.

[0023] Example 1: The external medicine for treating chronic inflammatory skin diseases in this example is mainly prepared from four traditional Chinese medicines: 50 g of Cortex Moutan, 50 g of Cortex Dictamni, 30 g of Fructus Psoraleae, and 50 g of Cortex Pseudolaricis.

[0024] The preparation method of the external medicine for treating chronic inflammatory skin diseases in this example includes the following steps: Take 50 g of Cortex Moutan, 50 g of Cortex Dictamni, 30 g of Fructus Psoraleae, and 50 g of Cortex Pseudolaricis, decoct twice with water. For the first time, add 12 times the amount of water and decoct for 1.5 hours, then filter; for the second time, add 10 times the amount of water and decoct for 1 hour, then filter. Combine the filtrates, and under the conditions of 70 °C and -0.08 MPa, concentrate under reduced pressure to a clear paste with a relative density of about 1.04 (50 °C), let it stand for 24 h, take the supernatant, filter, add 3 g of sodium benzoate, boil for 30 minutes, then add purified water to make up the volume to 250 ml, stir well, fill into containers, and thus obtain the aqueous external medicine for treating chronic inflammatory skin diseases.

[0025] Comparative Example 1: The external medicine for treating chronic inflammatory skin diseases in this comparative example is mainly prepared from five traditional Chinese medicines: 50 g of Cortex Moutan, 50 g of Cortex Dictamni, 30 g of Fructus Psoraleae, 50 g of Cortex Pseudolaricis, and 50 g of Cortex Fraxini.

[0026] The preparation method of the external medicine for treating chronic inflammatory skin diseases in this comparative example includes the following steps: Take 50 g of Cortex Moutan, 50 g of Cortex Dictamni, 30 g of Fructus Psoraleae, 50 g of Cortex Pseudolaricis, and 50 g of Cortex Fraxini, decoct twice with water. For the first time, add 12 times the amount of water and decoct for 1.5 hours, then filter; for the second time, add 10 times the amount of water and decoct for 1 hour, then filter. Combine the filtrates, and under the conditions of 70 °C and -0.08 MPa, concentrate under reduced pressure to a clear paste with a relative density of about 1.04 (50 °C), let it stand for 24 h, take the supernatant, filter, add 3 g of sodium benzoate, boil for 30 minutes, then add purified water to make up the volume to 250 ml, stir well, fill into containers, and thus obtain the aqueous external medicine for treating chronic inflammatory skin diseases.

[0027] Example 2: The external medicine for treating chronic inflammatory skin diseases in this example is prepared from four traditional Chinese medicines: 80 g of Cortex Moutan, 80 g of Cortex Dictamni, 40 g of Fructus Psoraleae, and 80 g of Cortex Pseudolaricis.

[0028] The preparation method of the external medicine for treating chronic inflammatory skin diseases in this example is the same as that in Example 1.

[0029] Example 3: The topical medicine for treating chronic inflammatory skin diseases in this example is prepared from four traditional Chinese medicines: 100 g of Cortex Moutan, 100 g of Cortex Dictamni, 50 g of Fructus Psoraleae, and 100 g of Cortex Pseudolaricis.

[0030] The preparation method of the topical medicine for treating chronic inflammatory skin diseases in this example is the same as that in Example 1.

[0031] To verify the technical effects of this application, biological experiments were conducted on the traditional Chinese medicine compositions of Example 1 and Comparative Example 1. Specifically, it includes: Healthy BALB / c mice aged 6 - 8 weeks were randomly divided into three groups: a model group, a control group (ZW), and a drug group (XQBP), with 8 mice in each group. Hair was removed from the same position on their backs within a range of 4×3 cm. Imiquimod was applied once daily. Two hours after applying imiquimod to the backs of the mice, the drug group (XQBP) was given the drug of Example 1 for application, and the control group (ZW) was given the drug of Comparative Example 1 for application. The drug group (XQBP) and the control group (ZW) were respectively applied with the drugs of Example 1 and Comparative Example 2 times daily.

[0032] Each group of mice was continuously administered and applied for 6 days, and the administration was stopped on the 7th day. Digital imaging was performed on the skin of the mouse backs, and the results are as Figure 1 shown. The clinical erythema, scales, and infiltration thickness of the mouse backs were recorded, and a PASI score was performed within the range of 0 - 4 points based on the clinical erythema, scales, and infiltration thickness. The scoring criteria are shown in Table 1.

[0033] Table 1 Psoriasis Area and Severity Index (PASI) Scoring Criteria

[0034] From Figure 1 it can be seen that the skin lesions of the model group were purplish - red patches, all skin lesions had scales, and the scales were relatively thick. The skin lesions were severely elevated, and the PASI score was 12 points; the skin lesions of the drug group (XQBP) were light - red patches, without scales, and the skin lesions were slightly elevated, and the PASI score was 2 points; while the skin lesions of the control group (ZW) were light - red patches, without scales, and the skin lesions were moderately elevated, and the PASI score was 3 points; obviously, the drug group (XQBP) and the control group (ZW) had a comparable or even better therapeutic effect on treating the imiquimod - induced psoriasis model, and could effectively improve the erythema, scales, and thickness of the dermatitis in psoriasis mice.

[0035] Skin lesions of each group of mice were stained with eosin - hematoxylin (HE) to observe the pathological changes of the skin lesions of the mice, and the results are as Figure 2As shown, the pathological results showed that the epidermis of the model group was significantly thickened, and a large number of inflammatory cells infiltrated the dermis. The epidermis of the psoriatic dermatitis mice in the drug group (XQBP) was significantly thinned, and there was no significant difference in improving the epidermal thickness of mice compared with the control group (ZW).

[0036] In summary, it can be seen that the topical drug for treating chronic inflammatory skin diseases of the present invention does not use Cortex Fraxini (long-term use of Cortex Fraxini may cause symptoms such as nausea and vomiting in humans and is not suitable for patients with spleen and stomach deficiency-cold). It can significantly reduce the toxic and side effects of the drug, has a wider range of suitable populations, and still has the technical effects of the applicant's previous patent (ZL201811121114.6), and can have a good therapeutic effect on chronic inflammatory skin diseases.

Claims

1. An external medicine for treating chronic inflammatory skin diseases, characterized in that: It is mainly made of the following raw material components by weight: 10-100 parts of Dictamni Cortex, 10-50 parts of Psoralea corylifolia, 10-100 parts of Cnidium monnieri Cortex, and 10-100 parts of Paeonia suffruticosa Cortex.

2. The external medicine for treating chronic inflammatory skin diseases according to claim 1, characterized in that: It is mainly made of the following raw material components by weight: 50 parts of Dictamni Cortex, 30 parts of Psoralea corylifolia, 50 parts of Cnidium monnieri, 50 parts of Paeonia suffruticosa root.

3. The external medicine for treating chronic inflammatory skin diseases according to claim 1, characterized in that: The dosage form of the external medicine includes lotion, ointment, cream, gel, tincture, patch, powder, shaker, spirit, oil, paste, plaster, film or aerosol.

4. A method for preparing an external medicine for treating chronic inflammatory skin diseases according to any one of claims 1 to 3, characterized in that: The following steps are involved: According to the formula ratio, Dictamni root bark, Psoralea corylifolia, Cnidium monnieri and Paeonia suffruticosa root bark are weighed, boiled twice with water, and the filtrates are combined; the filtrates are then concentrated under reduced pressure to a clear paste, which is the external medicine for treating chronic inflammatory skin diseases.

5. The preparation method according to claim 4, characterized in that: The clear paste is allowed to stand, and the supernatant is taken out, sodium benzoate is added and boiled, purified water is added to make up the volume, the mixture is stirred evenly, and the mixture is filled.

6. The preparation method according to claim 4 or 5, characterized in that: For the first decoction, add 10-15 times the amount of water, boil for 1-2 hours, and filter; for the second decoction, add 5-10 times the amount of water, boil for 0.5-1.5 hours.

7. The preparation method according to claim 4 or 5, characterized in that: The reduced pressure concentration was carried out at 65-75°C and -0.06 ~ -0.08MPa.

8. The preparation method according to claim 4 or 5, characterized in that: The relative density of the clear paste is 1.02-1.

06.

9. Use of the external medicine for treating chronic inflammatory skin diseases according to any one of claims 1 to 3 in the preparation of medicines for treating chronic inflammatory skin diseases.

Images