Topical Kampo medicine composition for treating psoriasis, its production method and use

Abstract

Provided is a topical Chinese herbal medicine composition for treating psoriasis, which contains, by parts by weight, 10 to 20 parts of Rubia cordifolia, 10 to 20 parts of Lithospermum erythrorhizon, 10 to 20 parts of Prunella vulgaris, and 30 to 50 parts of Glycyrrhiza uralensis Fisch. Each medicinal flavor contained in the Chinese herbal medicine composition has the functions of removing heat, detoxifying, cooling blood, and dispersing stasis, and has a remarkable therapeutic effect in the topical treatment of psoriasis.

Description

Technical Field

[0001] The present invention belongs to the technical field of psoriasis treatment, and particularly relates to an external traditional Chinese medicine composition for psoriasis treatment, its manufacturing method, and use.

Background Art

[0002] Psoriasis is a common chronic relapsing inflammatory skin disease. The basic skin lesions are erythema, papules, or plaques covered with multiple layers of silvery white scales. The occurrence sites are mostly on the body surface and head, and it is common for silvery white dry scales to repeatedly appear on the erythema. The cause of psoriasis is not completely clear, and it is a stubborn and difficult-to-treat disease, being listed as one of the 10 most stubborn diseases by the World Health Organization. Currently, most psoriasis treatments use topical medications such as keratoplastics and corticosteroid creams, while systemic medications include immunosuppressants, retinoids, antibiotics, corticosteroids, etc. These medications bring good short-term treatment effects for psoriasis, but have serious side effects with long-term use and a high recurrence rate. For example, methotrexate is the first-choice systemic treatment drug for psoriasis, and in some patients, mild adverse reactions such as diarrhea, nausea, loss of appetite, ulcers, drowsiness, and skin erosions occur after taking it. Retinoid drugs are mainly used for the treatment of moderate to severe psoriasis vulgaris, erythrodermic type, and pustular type psoriasis, but are ineffective for psoriatic arthritis. Common adverse reactions include skin and mucosal symptoms, eye toxicity, elevated liver enzymes or blood lipids, myelodysplasia, and teratogenicity, and it is necessary to monitor indicators such as blood lipids and growth curves. Biological agents (adalimumab, infliximab, efalizumab, etc.) are rapid and effective for psoriasis treatment, but have many side effects, for example, some patients may develop risks of nodular vasculitis, severe infections, heart failure, and malignant tumors after use. Topical glucocorticoids may cause symptoms such as skin atrophy, telangiectasia, atrophic striae, purpura, and hirsutism.

[0003] Chinese herbal medicines have shown certain advantages in improving the clinical symptoms of patients with mild to moderate psoriasis and reducing the recurrence rate. However, the oral treatment of Chinese herbal medicines has a long treatment cycle, so the compliance of patients is not high. Moreover, some medicines may potentially cause damage to the liver and kidneys, and in many cases, patients cannot take them for a long time. As people's requirements for the quality of life and physical health increase, more people are seeking more comprehensive treatment methods, and the clinical treatment plan for psoriasis needs to follow the principles of being safer, more effective, more economical, and more convenient.

Summary of the Invention

Problems to be Solved by the Invention

[0004] In consideration of this, the present invention aims to provide a Chinese herbal medicine composition for the treatment of psoriasis, in which each medicinal herb has a synergistic effect of removing heat, detoxifying, cooling the blood, and dispersing stasis, and has a remarkable therapeutic effect on the external treatment of psoriasis, and has the advantages of being safe, economical, and convenient to operate.

Means for Solving the Problems

[0005] To achieve the above object of the invention, the present invention provides the following technical solutions.

[0006] The present invention provides an external Chinese herbal medicine composition for the treatment of psoriasis, which contains raw materials of 10-20 parts of Rubia cordifolia, 10-20 parts of Lithospermum erythrorhizon, 10-20 parts of Prunella vulgaris, and 30-50 parts of Glycyrrhiza uralensis in parts by weight.

[0007] Preferably, the dosage forms of the external Chinese herbal medicine composition include liquid preparations, oil preparations, powder preparations, tinctures, lotions, creams, ointments, bath preparations, and gel preparations.

[0008] The present invention further provides a method for manufacturing the above external Chinese herbal medicine composition, which includes the step of mixing Rubia cordifolia, Lithospermum erythrorhizon, Prunella vulgaris, and Glycyrrhiza uralensis with an oil preparation, soaking them, frying them over a low fire until they turn brown, and removing the drug residues to obtain a medicinal oil.

[0009] Preferably, the oil agent includes sunflower oil or sesame oil.

[0010] Preferably, the solid-liquid ratio of the total of the four raw materials of madder, gromwell, selfheal and licorice root and the oil agent is 1 g: 4.1 ml to 9.2 ml.

[0011] Preferably, the immersion time is 24 h to 28 h.

[0012] The present invention further provides the use of the above-mentioned traditional Chinese medicine composition for external use in the manufacture of products for treating psoriasis.

[0013] Preferably, the traditional Chinese medicine composition for external use exerts a therapeutic effect by affecting the differentiation of keratinocytes, cytokine activity and / or the differentiation of epidermal cells.

[0014] Preferably, the traditional Chinese medicine composition for external use exerts a therapeutic effect by participating in cytokine receptor interaction, IL-17 signaling pathway, estrogen signaling pathway and / or protein digestion and absorption pathway.

[0015] Preferably, the product contains pharmaceuticals.

Advantages of the Invention

[0016] The beneficial effects of the present invention are as follows. In the traditional Chinese medicine composition for external use of the present invention, madder is the monarch drug that cools the blood, promotes blood circulation, removes stasis, and activates blood circulation; gromwell removes heat and detoxifies, cools the blood and stops bleeding; selfheal removes heat and detoxifies, and they are both ministerial drugs; licorice root is used as an adjuvant drug for detoxification and drug coordination. When the four drugs are combined, they can remove heat, detoxify, cool the blood, moisten dryness, and effectively treat psoriasis, having the advantages of clear and remarkable therapeutic effects, safety, economy, and convenient operation.

Brief Description of the Drawings

[0017]

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Modes for Carrying Out the Invention

[0018] The present invention provides an external traditional Chinese medicine composition for treating psoriasis, which contains raw materials of 10-20 parts of Rubia cordifolia, 10-20 parts of Lithospermum erythrorhizon, 10-20 parts of Prunella vulgaris, and 30-50 parts of Glycyrrhiza uralensis Fisch. by weight parts.

[0019] The present invention has no special restrictions on the specific sources of the above raw materials. In the present invention, the weight parts of the above raw materials are preferably 13-18 parts of Rubia cordifolia, 12-16 parts of Lithospermum erythrorhizon, 14-17 parts of Prunella vulgaris, and 35-45 parts of Glycyrrhiza uralensis Fisch., more preferably 14-16 parts of Rubia cordifolia, 14-15 parts of Lithospermum erythrorhizon, 15-16 parts of Prunella vulgaris, and 38-42 parts of Glycyrrhiza uralensis Fisch. The external traditional Chinese medicine composition for treating psoriasis of the present invention can preferably be manufactured into liquid preparations, oil preparations, powder preparations, tinctures, lotions, creams, ointments, bath preparations, gel preparations, etc.

[0020] The present invention further provides a method for manufacturing the above external traditional Chinese medicine composition, which includes the step of mixing Rubia cordifolia, Lithospermum erythrorhizon, Prunella vulgaris, and Glycyrrhiza uralensis Fisch. with an oil preparation, soaking them, stir-frying over a low heat until it turns brown, and removing the drug residues to obtain a medicinal oil.

[0021] In the present invention, the oil preparation preferably includes sunflower oil or sesame oil. The solid-liquid ratio of the total of the four raw materials of Rubia cordifolia, Lithospermum erythrorhizon, Prunella vulgaris, and Glycyrrhiza uralensis Fisch. to the oil preparation is preferably 1 g: 4.1 ml - 9.2 ml, more preferably 1 g: 5 ml - 8.5 ml. The present invention has no special restrictions on the specific sources of sunflower oil or sesame oil, and any product commonly commercially available in this field can be used. In the present invention, the soaking time is preferably 24 h - 28 h, more preferably 25 h - 26 h. In the present invention, there are no particular restrictions on the specific method for removing the drug residues, and any common removal method in this field can be used.

[0022] The present invention further provides the use of the above external traditional Chinese medicine composition in the manufacture of products for treating psoriasis.

[0023] In the present invention, the product preferably contains pharmaceuticals. The topical traditional Chinese medicine composition according to the present invention preferably exerts a therapeutic effect by affecting the differentiation of keratinocytes, cytokine activity and / or the differentiation of epidermal cells, and more preferably exerts a therapeutic effect by participating in cytokine receptor interaction, IL-17 signaling pathway, estrogen signaling pathway and / or protein digestion and absorption pathway.

[0024] The technical solutions provided by the present invention will be described in detail below with reference to the examples, but they should not be construed as limiting the scope of protection of the present invention.

[0025] In the following examples, unless otherwise specified, all are ordinary methods.

[0026] The materials, reagents, etc. used in the following examples can be obtained from commercial suppliers unless otherwise specified.

[0027] Example 1 10 g of Lithospermum erythrorhizon, 10 g of Rubia cordifolia, 10 g of Prunella vulgaris, and 50 g of Glycyrrhiza uralensis were mixed, immersed in 500 ml of sunflower oil for 24 hours, the medicinal materials were stir-fried over low heat until they turned brown, the drug residues were removed to obtain Four-Herb Oil, which was then placed in a refrigerator at 4°C for later use.

[0028] Example 2 20 g of Lithospermum erythrorhizon, 20 g of Rubia cordifolia, 20 g of Prunella vulgaris, and 30 g of Glycyrrhiza uralensis were mixed, then immersed in 550 ml of sesame oil for 24 hours, the medicinal materials were stir-fried over low heat until they turned brown, the drug residues were removed to obtain Four-Herb Oil, which was then placed in a refrigerator at 4°C for later use.

[0029] Example 3 15 g of Lithospermum erythrorhizon, 14 g of Rubia cordifolia, 16 g of Prunella vulgaris, and 40 g of Glycyrrhiza uralensis were mixed, then immersed in 600 ml of sunflower oil for 24 hours, the medicinal materials were stir-fried over low heat until they turned brown, the drug residues were removed to obtain Four-Herb Oil, which was then placed in a refrigerator at 4°C for later use.

[0030] Example 4 Male 6- to 8-week-old BABLc mice weighing 20 g ± 2 g were randomly divided into three groups of four mice each. (1) Blank control group (Control group): Every day, 62.5 mg of petrolatum cream was applied to the back and the inner and outer sides of both auricles of the mice. (2) Model group (IMQ group): 62.5 mg of 5% IMQ cream was applied to the back and the inner and outer sides of both auricles of the mice. Six hours later, 62.5 mg of petrolatum cream was applied to the back and the inner and outer sides of both auricles of the mice. (3) Sicao oil group (IMQ+SCY group): 62.5 mg of 5% IMQ cream was applied to the back and the inner and outer sides of both auricles of the mice. Six hours later, 150 μl of the sicao oil prepared in Example 1 was applied to the back and the inner and outer sides of both auricles of the mice. All treatments of the mice started from the day when IMQ was applied (day 0) and were performed once a day for 12 consecutive days.

[0031] The severity of skin inflammation on the back and ears of the mice, including erythema, thickness, and scales, was scored using the psoriasis area and severity index (PASI). The scores indicated the severity as 0 (none), 1 (mild), 2 (moderate), 3 (severe), and 4 (very severe). The mice were fasted before sample collection and allowed to drink water for 12 hours. At the end of the 13th day of the experiment, the mice were sacrificed with CO2, and the skin lesions on the ears and the back were collected for further experiments, respectively.

[0032] Experimental results (1) Sicao oil can improve the skin lesions on the back and ears of IMQ-induced psoriatic-like mice As shown in the results in Figure 1, on the 12th day of IMQ modeling, petrolatum ointment was externally applied to the control group, and no erythema, scales, or skin thickening was observed on the skin of the back and ears. However, the mice in the IMQ group showed obvious erythema, scales, and skin thickening on the back and ears. Compared with the control group, the PASI score of the IMQ group was significantly higher, and the ears were significantly swollen. Compared with the IMQ group, the PASI score and ear swelling of the mice in the IMQ+SCY group decreased. (2) Sicao oil can improve the histopathology of the IMQ-induced psoriatic-like mouse model As shown in Figure 2, the pathological tissue sections of the backs and ears of the mice in each group showed that on the 12th day of IMQ modeling, the skin epidermal layers of the backs and ears of the mice in the control group were thin and no inflammatory cell infiltration occurred. Compared with the control group, the skin of the backs and ears of the mice in the IMQ group showed hyperkeratosis with parakeratosis, microabscesses of neutrophils were seen in the parakeratotic areas, the granular layer was significantly reduced, the basal layer was thickened, and the epidermal projections extended downward. Infiltration of neutrophils, lymphocytes, etc. was observed (p<0.001). The inflammatory cell infiltration and epidermal hyperplasia of the skin of the backs and ears of the mice in the IMQ+SCY group were reduced (p<0.05).

[0033] Example 5 In order to investigate the mechanism of action of Sicao oil in the treatment of psoriasis of the present invention and provide a theoretical basis for the external use of Sicao oil, the following mRNA-seq analysis was performed here.

[0034] 1. Database construction process (1) Total RNA quality inspection Using the RNeasy Mini Kit (Cat#74106, Qiagen), total RNA extraction was performed from the mouse samples of the IMQ group and the IMQ+SCY group in Example 4 according to the standard operating procedures provided by the manufacturer. The quality of the total RNA was inspected using a NanoDrop ND-2000 spectrophotometer and an Agilent Bioanalyzer 4200 (Agilent technologies, Santa Clara, CA, US), and the RNA that passed the quality inspection could be used for subsequent library construction. (2) Library construction and quality inspection For specific eukaryotic species, rRNA was removed using magnetic beads. Next, the rRNA-depleted RNA was fragmented, double-stranded cDNA was synthesized, the second strand was degraded, the ends were repaired, A was added to the 3' end, and an adapter was ligated to amplify the experiment. The constructed library was measured using a Qubit® 2.0 fluorometer for concentration and an Agilent 2100 for size. (3) Sequencing on the machine The qualified libraries were ready for Illumina sequencing, and the sequencing method was PE150. The basic principle of sequencing was Sequencing by Synthesis (SBS). A flow cell with clusters was placed in the machine, and four fluorescently labeled dNTPs, DNA polymerase, and adapter primers were added to the flow cell for amplification. Each time a fluorescently labeled dNTP was added as each sequencing cluster extended its complementary strand, the corresponding fluorescence was emitted. The sequencer captured the fluorescence signal and converted the optical signal into sequence peaks via computer software to obtain the sequence information of the fragment under test.

[0035] 2. Data analysis process As shown in Figure 3.

[0036] 3. Experimental results (1) Identification of differential gene expression after the intervention of Sicao oil A total of 718 differential genes were identified by mRNA-seq analysis. Differential gene screening criteria: According to Foldchange = 2-fold and p-value < 0.05, 160 up-regulated genes and 129 down-regulated genes were screened in the IMQ+SCY group and the IMQ group. The results are shown in the volcano plot (Figure 4A) and the heat map of cluster analysis (Figure 4B). (2) The functions and biological pathways of differential genes were revealed by GO and KEGG enrichment analysis

[0037] To clarify the functions and biological pathways of differentially expressed proteins (DEPs), GO and KEGG enrichment analyses were performed on the differentially expressed genes in the psoriatic skin lesions of mice after SCY intervention in the IMQ+SCY group. GO analysis showed that the DEPs in the IMQ+SCY group were mainly related to keratinocyte differentiation, cytokine activity, epidermal cell differentiation, etc. (Figure 5A). KEGG enrichment analysis showed that the DEPs in the IMQ+SCY group were mainly involved in cytokine receptor interaction, IL-17 signaling pathway, estrogen signaling pathway, protein digestion and absorption, etc. (Figure 5B).

[0038] It should be noted that the above are only preferred embodiments of the present invention. Those skilled in the art can make some improvements and modifications without departing from the principle of the present invention, and these improvements and modifications should also be regarded as within the protection scope of the present invention.

Claims

1. An external traditional Chinese medicine composition for treating psoriasis, characterized by containing the following raw materials in parts by weight: 10 to 20 parts of Rubia cordifolia, 10 to 20 parts of Lithospermum erythrorhizon, 10 to 20 parts of Prunella vulgaris, and 30 to 50 parts of Glycyrrhiza uralensis Fisch.

2. The external traditional Chinese medicine composition according to claim 1, wherein the dosage forms of the external traditional Chinese medicine composition include liquid preparations, oils, powders, tinctures, lotions, creams, ointments, bath preparations, and gels.

3. The method for manufacturing the external traditional Chinese medicine composition according to claim 1, comprising the steps of mixing Rubia cordifolia, Lithospermum erythrorhizon, Prunella vulgaris, and Glycyrrhiza uralensis Fisch. with an oil, soaking them, stir-frying over a low heat until it turns brown, and removing the drug residues to obtain a medicinal oil.

4. The manufacturing method according to claim 3, wherein the oil includes sunflower oil or sesame oil.

5. The manufacturing method according to claim 3, wherein the solid-liquid ratio of the total of the four raw materials of Rubia cordifolia, Lithospermum erythrorhizon, Prunella vulgaris, and Glycyrrhiza uralensis Fisch. to the oil is 1 g: 4.1 ml to 9.2 ml.

6. The manufacturing method according to claim 3, wherein the soaking time is 24 hours to 28 hours.

7. Use of the external traditional Chinese medicine composition according to claim 1 in the manufacture of a product for treating psoriasis.

8. The use according to claim 7, wherein the external traditional Chinese medicine composition exerts a therapeutic effect by affecting the differentiation of keratinocytes, cytokine activity, and / or the differentiation of epidermal cells.

9. The use according to claim 7, wherein the external traditional Chinese medicine composition exerts a therapeutic effect by participating in cytokine receptor interaction, the IL-17 signaling pathway, the estrogen signaling pathway, and / or the protein digestion and absorption pathway.

10. The use according to claim 7, wherein the product contains a pharmaceutical.

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