Traditional Chinese medicine composition for treating psoriasis and application thereof

Abstract

The invention belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating psoriasis and application thereof, and the traditional Chinese medicine composition at least comprises the following two components in parts by weight: 3-6 parts of lithospermum, 2-5 parts of scutellaria baicalensis, 2-4 parts of semen armeniacae amarae, 1-2 parts of rheum officinale and 1-2 parts of liquorice. Compared with the prior art, the invention solves the problem that the external traditional Chinese medicine composition for treating psoriasis is lacked in the prior art, and provides the external traditional Chinese medicine composition capable of relieving clinical symptoms of patients with psoriasis vulgaris and improving the life quality of the patients.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition for treating psoriasis and application thereof. Background Art

[0002] Psoriasis, known as "white psoriasis" in traditional medicine, is characterized by widespread erythema, covered with scales, often accompanied by excessive proliferation and abnormal differentiation of keratinocytes. It is a chronic and immune-related skin disease that affects a large number of people worldwide. In recent years, the incidence of psoriasis has been on the rise. According to the GBD2019 study, the prevalence of psoriasis in different countries ranges from 0.09% to 3.34%, of which China is 0.56%. In addition, psoriasis also has a huge impact on public health and creates an economic burden due to its high prevalence and long-term management costs. Therefore, actively seeking safe and effective methods to treat psoriasis remains the main goal at present.

[0003] Today, its etiology and pathogenesis are still unclear. Modern medicine believes that immune system abnormalities are the main cause of psoriasis. Psoriasis is often related to abnormal expression of angiogenic inflammatory factors, chemokines, vascular endothelial growth factor (VEGF), and interleukin-17 (IL-17) caused by innate and acquired immune disorders. The disease can also progress due to internal factors such as obesity and diabetes or external factors such as air pollution. At present, the clinical treatment of psoriasis by Western medicine mainly uses glucocorticoids, vitamin D analogs, phototherapy, and systemic therapy. However, long-term use of glucocorticoids can induce metabolic disorders, osteoporosis, and increase infection and other side effects, which in turn affect most major organ systems; systemic treatment with methotrexate has the risk of causing liver damage; the use rate of biological agents in my country has been high in recent years. Its efficacy is acceptable, but the disease is prone to recurrence. There are also reports of adverse reactions such as injection site reactions, upper respiratory tract infections, urinary tract infections, fungal infections, and herpes simplex virus infections. Traditional Chinese medicine is effective in treating psoriasis, can reduce toxic side effects, is safe and low-cost, making Chinese medicine increasingly prominent in the treatment of psoriasis.

[0004] Traditional Chinese medicine is currently widely used in the treatment of psoriasis and has achieved good therapeutic effects. It has an irreplaceable position in both oral and external treatment methods. Chinese medicine external ointment is a type of preparation that extracts Chinese medicine raw materials and makes the active ingredients and matrix into semi-solid or nearly solid preparations. The external ointment can quickly pass through the skin and / or mucous membranes to achieve local or systemic therapeutic effects. Compared with oral decoctions, external ointments can avoid the first-pass effect of the liver caused by Chinese medicine decoctions, as well as irritation to the gastrointestinal tract. The active ingredients of the medicine can reach the lesions more directly and quickly achieve therapeutic effects.

[0005] The combination of Chinese medicine directly determines the effect of Chinese medicine topical ointment. Most doctors in ancient books believe that psoriasis is related to external evils such as wind, heat, cold, and dampness, and is difficult to cure. Since the Ming and Qing Dynasties, doctors have gradually begun to pay attention to the "blood-based treatment" of this disease on the basis of dispelling wind and dampness, such as the method of clearing heat, detoxifying, and cooling blood in the "Zhengzhi Zhunsheng" of the Ming Dynasty. Professor Qin Wanzhang and Professor Li Bin inherited the ideas of their predecessors, combined with their own clinical practice, integrated new knowledge, and proposed the idea of ​​"new blood argumentation" for psoriasis in traditional Chinese medicine, that is, "blood heat and yang floating first, blood stasis throughout", which provides a theoretical basis for clinical diagnosis and treatment of traditional Chinese medicine. At present, there is still a lack of a Chinese medicine composition and corresponding topical preparations that can be used to effectively treat psoriasis, and it is necessary to study and develop them. Summary of the invention

[0006] The purpose of the present invention is to solve at least one of the above problems and provide a Chinese medicine composition for treating psoriasis and its application. The present invention is based on Xia's surgical theory of "blood heat and yang floating", takes "clearing heat and cooling blood" as the main treatment principle of the disease, and solves the lack of external Chinese medicine compositions for treating psoriasis in the prior art. This solution provides an external Chinese medicine composition that can relieve the clinical symptoms of patients with psoriasis vulgaris and improve the quality of life of patients.

[0007] The purpose of the present invention is achieved through the following technical solutions:

[0008] The first aspect of the present invention discloses a Chinese medicine composition for treating psoriasis, comprising at least two components in parts by weight: 3-6 parts of lithospermum officinale, 2-5 parts of scutellaria baicalensis, 2-4 parts of bitter almonds, 1-2 parts of rhubarb and 1-2 parts of liquorice.

[0009] Preferably, the Chinese medicine composition comprises the following components in parts by weight: 5 parts of Lithospermum officinale, 3 parts of Scutellaria baicalensis, 3 parts of Apricot kernel, 1 part of Rhubarb and 1 part of Licorice.

[0010] Preferably, the lithospermum is the dried root of Arnebia euchroma (Royle) Johnst or A. guttata Bunge of the Boraginaceae family. It is cold in nature, sweet and salty in taste, and enters the heart and liver meridians.

[0011] Preferably, the scutellaria baicalensis is the dried root of Scutellaria baicalensis Georgi, a plant of the Labiatae family. It is cold in nature, bitter in taste, and enters the lung, gallbladder, spleen, large intestine, and small intestine meridians.

[0012] Preferably, the bitter almond is the dried mature seeds of Prunus armeniaca Lvar. ansu Maxim, a plant of the Rosaceae family. It is slightly warm in nature, bitter in taste, slightly toxic, and enters the lung and large intestine meridians.

[0013] Preferably, the rhubarb is the dried root and rhizome of medicinal rhubarb (Rheum officinale Bai), which is cold in nature, bitter in taste, and enters the spleen, stomach, large intestine, liver, and pericardium meridians.

[0014] Preferably, the licorice is the dried root and rhizome of the leguminous plant licorice (Glycyrrhiza uralensis fisch). It is flat in nature, sweet in taste, and enters the heart, lung, spleen, and stomach meridians.

[0015] Preferably, the Chinese medicine composition is composed of the following components in parts by weight: 5 parts of Lithospermum officinale, 3 parts of Scutellaria baicalensis, 3 parts of Apricot kernel, 1 part of Rhubarb and 1 part of Licorice;

[0016] in:

[0017] The lithospermum officinale is the dried root of the plant lithospermum officinale of Xinjiang or Inner Mongolia;

[0018] The scutellaria baicalensis is the dried root of the scutellaria baicalensis plant of the Labiatae family;

[0019] The bitter almonds are the dried mature seeds of the Rosaceae plant Prunus armeniaca.

[0020] The rhubarb is the dried root and rhizome of medicinal rhubarb;

[0021] The licorice is the dried root and rhizome of the leguminous plant licorice.

[0022] The second aspect of the present invention discloses a use of any of the above-described traditional Chinese medicine compositions for treating psoriasis in the preparation of a preparation for treating psoriasis.

[0023] Preferably, the preparation is in the form of an external ointment.

[0024] The working principle of the present invention is:

[0025] The present invention is compatible according to the prescription principle of monarch, minister, assistant and envoy of traditional Chinese medicine. In the composition, lithospermum officinale is the monarch; scutellaria baicalensis is the minister; bitter almond and rhubarb are both adjuvants, and liquorice is the envoy. In the composition, lithospermum officinale is the monarch, which is used to clear away heat and cool blood, promote blood circulation and detoxify, and has a significant therapeutic effect on blood heat and blood-dryness type psoriasis in the late stage of blood heat. Scutellaria baicalensis is the minister, which is used to clear away heat and dry dampness, purge fire and detoxify, and help the monarch medicine to strengthen the effect of clearing heat and detoxification. Rhubarb and bitter almond are both adjuvants, which are used to clear, purge fire, cool blood and moisturize dryness, and can be used to treat skin arthritis and itching caused by blood heat. Licorice is the envoy, which harmonizes the properties of various medicines. The above-mentioned traditional Chinese medicines play a role in improving psoriasis through drug interactions.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] 1. Experiments have shown that the Chinese medicine composition of the present invention can reduce the Psoriasis area and severity index (PASI) score of the back skin of mice, reduce epidermal thickening, improve inflammatory response, inhibit the expression of IL-17A and TNF-α, and increase the expression of IL-10. Its mode of action is to regulate the expression of key proteins in the PI3K / Akt / mTorC1 signaling pathway.

[0028] 2. The Chinese medicine combination of the present invention is applied externally, and animal experiments have confirmed that its efficacy is not inferior to that of the positive drug calcipotriol ointment. In addition, external administration can prevent the drug from entering the systemic blood circulation, and the occurrence of adverse reactions is less at the same dose.

[0029] 3. The external Chinese medicine composition ointment of the present invention also includes auxiliary materials. The Chinese medicine composition is well-matched and has strong clinical applicability. It can effectively improve the relevant symptoms of psoriasis patients, and the mouse experiment has obvious efficacy and low incidence of adverse reactions. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 The following are the observations of the efficacy of the mouse psoriasis modeling and Ziqin ointment (i.e., the Chinese medicine composition) in Test Example 1: A. Changes in the skin lesions on the back of mice before and after treatment with Ziqin ointment and calcipotriol under IMQ modeling; B. Changes in PASI scores during mouse modeling and treatment; C. HE staining results of the back skin of mice; D. Analysis of the epidermal thickness and Baker score results of the skin lesions in the pathological sections of mice. Note: **P<0.01, ****P<0.0001; Data are presented as mean ± standard deviation; n=3 / group.

[0031] Figure 2 These are pathological sections of the spleen, liver, kidney, heart, lung, and testis of the normal group mice and the medication group mice in Test Example 2.

[0032] Figure 3 Observation of the improvement of skin lesions of psoriasis mice by Ziqin ointment in Test Example 3: A. 7-day changes in the back skin of four groups of mice; B. Changes in the PASI scores of the back skin of four groups of mice; C. 7-day changes in the ears of four groups of mice; D. Changes in the ear thickness of four groups of mice; E. HE staining of the back skin of four groups of mice on the 8th day; F. Analysis of the results of epidermal thickness of skin lesions in pathological sections of four groups of mice. Note: **P<0.01, ***P<0.001, ****P<0.0001; Data are presented as mean ± standard deviation; n=3 / group.

[0033] Figure 4The efficacy of Ziqin paste on psoriasis mice in test example 3 is observed: A. The expression of IL-17A in the serum of four groups of mice; B. The expression of IL-10 in the serum of four groups of mice; C. The expression of TNF-α in the serum of four groups of mice; D. Comparison of the appearance of the five internal organs of four groups of mice; E. Comparison of the appearance of the spleen of four groups of mice; F. Comparison of the weight of the spleen of four groups of mice. Note: *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001; Data are presented as mean ± standard deviation; n=3 / group.

[0034] Figure 5 In Test Example 3, Ziqin paste improves psoriasis by regulating the expression of key proteins in the PI3K / Akt / mTORC1 signaling pathway: A. Results of immunohistochemistry of the back skin of four groups of mice; B. Quantitative results of immunohistochemistry; C. Differences in protein expression in four groups of mice; D. Quantitative results of WB in four groups of mice; E. Relative mRNA expression of mTORC1, Akt1, and PI3K in four groups of mice. Note: *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001; Data are presented as mean ± standard deviation; n=3 / group. DETAILED DESCRIPTION

[0035] The present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments, but the present invention is not limited in any way. Any changes or substitutions made based on the teachings of the present invention belong to the protection scope of the present invention.

[0036] In the following description, unless otherwise specified, the reagents used are conventional commercially available products, and the methods used are well known in the art.

[0037] The first purpose of the present invention is to provide an external Chinese medicine composition that can relieve the clinical symptoms of patients with psoriasis vulgaris and improve the quality of life of patients. A further purpose is to provide a preparation method and specific clinical application thereof.

[0038] The present invention provides a Chinese medicine composition for external use of ointment for treating psoriasis, which is prepared from at least two raw materials in parts by weight: 3-6 parts of lithospermum officinale, 2-5 parts of scutellaria baicalensis, 2-4 parts of bitter almonds, 1-2 parts of rhubarb, and 1-2 parts of liquorice. Preferably, the composition is 5 parts of lithospermum officinale, 3 parts of scutellaria baicalensis, 3 parts of bitter almonds, 1 part of rhubarb, and 1 part of liquorice.

[0039] Lithospermum officinale is the dried root of Arnebia euchroma (Royle) Johnst or A. guttata Bunge, both of which belong to the Boraginaceae family. It is cold in nature, sweet and salty in taste, and enters the heart and liver meridians.

[0040] Scutellaria baicalensis is the dried root of Scutellaria baicalensis Georgi, a plant of the Labiatae family. It is cold in nature, bitter in taste, and enters the lung, gallbladder, spleen, large intestine, and small intestine meridians.

[0041] Bitter almonds are the dried mature seeds of the Rosaceae plant Prunus armeniaca Lvar. ansu Maxim. They are slightly warm in nature, bitter in taste, slightly toxic, and enter the lung and large intestine meridians.

[0042] Rhubarb is the dried root and rhizome of the medicinal rhubarb (Rheum officinale Bai). It is cold in nature, bitter in taste, and enters the spleen, stomach, large intestine, liver, and pericardium meridians.

[0043] Licorice is the dried root and rhizome of the legume plant Glycyrrhiza uralensis fisch. It is flat in nature, sweet in taste, and enters the heart, lung, spleen, and stomach meridians.

[0044] The ointment is prepared by the following process:

[0045] (1) soaking lithospermum officinale for later use, soaking the Chinese medicinal materials other than lithospermum officinale in sesame oil according to weight, at a temperature not exceeding 140° C., and decocting over a slow fire for 5-10 minutes;

[0046] (2) Pour the soaked lithospermum into the oil, keep the temperature between 100-140℃, and boil for 5-10 minutes;

[0047] (3) After standing for 24 hours, filter to separate the drug residue from the filtered drug oil;

[0048] (4) After adding beeswax to the medicinal oil, heat it in a water bath while stirring evenly to completely dissolve the beeswax. After cooling, a paste is formed to obtain a traditional Chinese medicine ointment for treating psoriasis.

[0049] Preferably, the weight ratio of the sesame oil to the total weight of the traditional Chinese medicine composition in (1) is 60:14.

[0050] Preferably, the weight ratio of beeswax to the obtained medicinal oil in (4) is 3:10.

[0051] The present invention is compatible according to the prescription principle of monarch, minister, assistant and envoy of traditional Chinese medicine. In the composition, lithospermum officinale is the monarch; scutellaria baicalensis is the minister; bitter almond and rhubarb are both adjuvants, and liquorice is the envoy. In the composition, lithospermum officinale is the monarch, which is used to clear away heat and cool blood, promote blood circulation and detoxify, and has a significant therapeutic effect on blood heat and blood-dryness type psoriasis in the late stage of blood heat. Scutellaria baicalensis is the minister, which is used to clear away heat and dry dampness, purge fire and detoxify, and help the monarch medicine to strengthen the effect of clearing heat and detoxification. Rhubarb and bitter almond are both adjuvants, which are used to clear, purge fire, cool blood and moisturize dryness, and can be used to treat skin arthritis and itching caused by blood heat. Licorice is the envoy, which harmonizes the properties of various medicines. The above-mentioned traditional Chinese medicines play a role in improving psoriasis through drug interactions.

[0052] Example 1

[0053] Composition: Lithospermum officinale 30g, Scutellaria baicalensis 18g, Bitter Apricot Kernel 18g, Rhubarb 6g, Licorice 6g.

[0054] Weigh each medicinal ingredient in the composition according to the combined amount, soak lithospermum in water, put the remaining medicinal ingredients in 334g sesame oil, and boil for 10 minutes, keeping the temperature no higher than 140°C, pour the soaked lithospermum into a pot, keep the temperature at about 120°C, and boil for 6 minutes; filter after leaving for 24 hours, and discard the residue; take 200g of medicinal oil and add 60g of beeswax, heat in a water bath while stirring continuously, and pour into a packaging container while the beeswax is completely dissolved, and after cooling and solidifying, you can get the traditional Chinese medicine external ointment for treating psoriasis - Ziqin ointment.

[0055] Example 2

[0056] Composition: Lithospermum officinale 45g, Scutellaria baicalensis 36g, Bitter Apricot Kernel 27g, Rhubarb 9g, Licorice 9g.

[0057] Weigh each medicinal ingredient in the composition according to the combined amount, soak lithospermum in water, put the remaining medicinal ingredients in 540g sesame oil, and boil for 10 minutes, keeping the temperature no higher than 140°C, pour the soaked lithospermum into a pot, keep the temperature at about 120°C, and boil for 10 minutes; filter after leaving for 24 hours, and discard the residue; take 400g of medicinal oil and add 120g of beeswax, heat in a water bath while stirring continuously, and pour into a packaging container while the beeswax is completely dissolved, and after cooling and solidifying, you can get the traditional Chinese medicine external ointment for treating psoriasis - Ziqin ointment.

[0058] Example 3

[0059] Composition: Lithospermum officinale 45g, Scutellaria baicalensis 36g, Bitter Apricot Kernel 27g.

[0060] Weigh each medicinal ingredient in the composition according to the combined amount, soak lithospermum in water, put the remaining medicinal ingredients in 463g sesame oil, and boil for 10 minutes, keeping the temperature no higher than 140°C, pour the soaked lithospermum into a pot, keep the temperature at about 120°C, and boil for 10 minutes; filter after leaving for 24 hours, and discard the residue; take 400g of medicinal oil and add 120g of beeswax, heat in a water bath while stirring continuously, and pour into a packaging container while the beeswax is completely dissolved, and after cooling and solidifying, you can get the traditional Chinese medicine external ointment for treating psoriasis - Ziqin ointment.

[0061] Example 4

[0062] Composition: Lithospermum officinale 45g, Scutellaria baicalensis 36g, Rhubarb 9g.

[0063] Weigh each medicinal ingredient in the composition according to the combined amount, soak lithospermum in water, put the remaining medicinal ingredients in 386g sesame oil, and boil for 10 minutes, keeping the temperature no higher than 140°C, pour the soaked lithospermum into a pot, keep the temperature at about 120°C, and boil for 10 minutes; filter after leaving for 24 hours, and discard the residue; take 400g of medicinal oil and add 120g of beeswax, heat in a water bath while stirring continuously, and pour into a packaging container while the beeswax is completely dissolved, and after cooling and solidifying, you can get the traditional Chinese medicine external ointment for treating psoriasis - Ziqin ointment.

[0064] Example 5

[0065] Composition: Lithospermum officinale 45g, Scutellaria baicalensis 36g, Licorice root 9g.

[0066] Weigh each medicinal ingredient in the composition according to the combined amount, soak lithospermum in water, put the remaining medicinal ingredients in 386g sesame oil, and boil for 10 minutes, keeping the temperature no higher than 140°C, pour the soaked lithospermum into a pot, keep the temperature at about 120°C, and boil for 10 minutes; filter after leaving for 24 hours, and discard the residue; take 400g of medicinal oil and add 120g of beeswax, heat in a water bath while stirring continuously, and pour into a packaging container while the beeswax is completely dissolved, and after cooling and solidifying, you can get the traditional Chinese medicine external ointment for treating psoriasis - Ziqin ointment.

[0067] Comparative Example 1

[0068] The difference from Example 1 is that the lithospermum officinale is not soaked in water, and all the medicinal ingredients are directly put into the pot and decocted for 10 minutes.

[0069] Through pharmacodynamic experiments, the prepared Chinese medicine composition was made into an ointment for administration to evaluate the therapeutic effect of the Chinese medicine composition of the present invention on a mouse psoriasis model.

[0070] Test Example 1: Study on the efficacy of Chinese medicine composition in treating psoriasis:

[0071] 1. Experimental Methods

[0072] PASI score is an important indicator for monitoring and evaluating the severity and improvement of psoriasis in clinical and pharmacological experiments; hematoxylin-eosin (HE) staining can observe the pathological changes of back lesions and evaluate the incidence of psoriasis. In this experiment, an animal model of psoriasis was induced by imiquimod, and the Chinese medicine composition ointment prepared in Example 1 (Zqin Gao, abbreviated as ZQG) and Comparative Example 1 was administered for intervention, and the effect and efficacy of the Chinese medicine composition in intervening psoriasis were studied by H&E staining.

[0073] 1. Drugs and reagents: 5% imiquimod ointment (for modeling), calcipotriol ointment (administered to the positive group, abbreviated as Cal in the following description), the Chinese medicine composition ointment prepared in Example 1 (administered to the experimental group, abbreviated as ZQG in the following description), and the Chinese medicine combination ointment prepared in Comparative Example 1.

[0074] 2. Experimental grouping: SPF-grade C57BL / 6 mice were adaptively fed for one week and then randomly divided into 8 groups according to body weight, with 3 mice in each group, including a normal group (Blank), an imiquimod group (IMQ group), a positive group (IMQ+Cal group), an experimental group (IMQ+ZQG group), and a group of comparative example 1.

[0075] 3. Modeling and drug administration: Shave the hair on the back of mice 24 hours before the start of the experiment to ensure that the back skin is not damaged.

[0076] After starting the experiment:

[0077] The mice in the normal group were not treated;

[0078] 62.5 mg of 5% imiquimod cream was evenly applied on the back of mice in the imiquimod group once a day for 7 consecutive days;

[0079] The experimental group mice were evenly smeared with 62.5 mg of 5% imiquimod cream on the back, and then smeared with 100 mg of the Chinese medicine composition ointment after an interval of 6 hours, once a day for 7 consecutive days;

[0080] 62.5 mg of 5% imiquimod cream was evenly applied on the back of mice in the positive group, and then 100 mg of calcipotriol was applied after an interval of 6 hours, once a day for 7 consecutive days.

[0081] Except for the different ointments used in the comparative example, the other operations were the same as those in the experimental group.

[0082] The PASI scores of the mice's backs were recorded daily. All mice were sacrificed on day 8 and skin samples were collected. The skin samples were fixed in 4% paraformaldehyde and embedded in paraffin for histomorphological analysis.

[0083] 4. Refer to the PASI scoring standard for the area and severity index of clinical psoriasis (as shown in Table 1), and a dedicated person will blindly select and observe the changes in the skin lesions of each group of mice every day to minimize experimental errors. According to the PASI scoring standard (erythema, 0-4; scaling, 0-4; skin thickening, 0-4), the total score of psoriasis-like changes on the back of the experimental animals is evaluated every day (scaling + erythema + skin thickening, 0-12), and a psoriasis score trend chart is drawn after statistical analysis to observe the dynamic changes in the skin lesions of mice.

[0084] Table 1 PASI scoring criteria

[0085]

[0086] 5. The psoriasis-like changes in each HE-stained section were evaluated by Baker score (Table 2) to observe the condition of the back epidermis of the mice.

[0087] Table 2 Baker score table

[0088]

[0089] 2. Results Analysis

[0090] 1. If Figure 1 As shown in A, through naked eye observation, the skin of mice in the normal group remained smooth, and there was no dry scale, erythema, etc. on the epidermis; the psoriasis-like model was formed 7 days after modeling and administration in the imiquimod group; compared with the imiquimod group (hereinafter referred to as the model group), the psoriasis skin lesions in the Chinese medicine composition group of the present invention were lighter, and the mice had thin and less scales, and the scale layering phenomenon was not obvious, which was no significant difference from the positive group. According to these results, it can be preliminarily judged that the Chinese medicine composition of the present invention can alleviate the skin lesions of psoriasis-like mice.

[0091] 2. This experiment used PASI scores to compare the severity of skin lesions on the back of mice in the drug-treated group and the model group.

[0092] The sum of the scores of erythema, scaling, and skin thickening in the normal group was always 0.

[0093] On the third day of modeling, the mice in the model group gradually developed psoriasis-like lesions on their skin: erythema, scaling, and thickening of the skin on the back, which gradually increased in severity and area over time. From the fifth to the seventh day, the PASI scores in erythema, scaling, thickening of lesions, and the total score were significantly higher than those in the normal group, indicating that the model was successfully established.

[0094] Compared with the mice in the imiquimod group at the same period, the skin erythema, scaling and thickening of skin lesions in the positive group and experimental group mice were alleviated, and the total scores of these three items were lower than those in the model group from the 5th to the 7th day.

[0095] Compared with the imiquimod group, the PASI score of the back of mice began to decrease on the 6th day after Ziqin ointment treatment, while the former was still increasing. Figure 1 B. The above results show that the experimental group and the positive group can improve the erythema, scaling and thickening of the mouse skin to varying degrees.

[0096] 4. Pathological analysis of psoriasis-like mouse skin lesions by HE staining (e.g. Figure 1C, D): Compared with the imiquimod group, the epidermal thickness of mice was significantly reduced after treatment with the Chinese medicine composition, and the spinous process was elongated and the dermal papilla was improved (P<0.0001). The Baker score results showed that compared with the imiquimod group, the Baker score was significantly reduced after treatment with the Chinese medicine composition (P<0.0001). Compared with the calcipotriol group, there was no significant difference in epidermal thickness and Baker score in the Ziqin cream group (P>0.05).

[0097] Test Example 2: Effects of Chinese medicine composition on the internal organs of mice:

[0098] 1. Experimental Methods

[0099] HE staining can be used to observe whether there are pathological changes in the mouse internal organs, thereby evaluating the safety of the drug. In this experiment, mice were given the Chinese medicine composition paste prepared in Example 1 for intervention, and H&E staining was used to study whether the Chinese medicine composition had an effect on the mouse internal organs.

[0100] 1. Drugs and reagents: The Chinese medicine composition ointment prepared in Example 1 (administered to the experimental group).

[0101] 2. Experimental grouping: SPF-grade C57BL / 6 mice were fed adaptively for one week and then randomly divided into two groups according to body weight, with 3 mice in each group, namely the normal group (Blank) and the medication group (Chinese medicine composition paste, ZQG).

[0102] 3. Administration: Shave the hair on the back of the mice 24 hours before the start of the experiment to ensure that the back skin is not damaged. The mice in the normal group were not treated after the start of the experiment. 100 mg of the Chinese medicine composition ointment was evenly applied to the back of the mice in the medication group, once a day, for 7 consecutive days. All mice were killed on the 8th day and samples were collected. The organ samples were fixed in 4% paraformaldehyde and embedded in paraffin for tissue morphological analysis.

[0103] 2. Experimental Results

[0104] We used the Chinese medicine composition ointment alone to apply to the back skin and ears of mice, and after 7 days, the spleen, liver, kidney, heart, lung, and testis were taken to prepare HE-stained pathological sections ( Figure 2). The results showed that the spleen capsule was not thickened, the shape of the spleen follicles was uniform, the red and white pulp structures were normal and clearly visible, no pathological structure was found, and there was no difference from the control group. The liver structure was neatly arranged, the hepatic sinusoids, hepatic lobules and portal areas were clearly visible, no pathological structure was found, and there was no difference from the control group. The renal cortex, medulla, glomerulus, renal tubules were clearly visible, and the structure was normal, and there was no difference from the control group. The endocardium, epicardium and myometrium had normal structures. The myocardial fibers were arranged in an orderly manner, and no obvious atrophy, degeneration, hypertrophy and necrosis were found under the pathological section microscope, which was no different from the control group. There was no obvious congestion of the alveolar wall capillaries, the alveoli were uniform in size, no inflammatory exudate was found in the alveolar cavity, and the structure of each bronchiole was normal, which was no different from the control group. The testicular capsule was normal, no inflammatory infiltration was found, and the structure of the seminiferous tubules was normal, which was no different from the control group.

[0105] Test Example 3: Verification of the mechanism of the Chinese medicine composition in treating psoriasis through animal experiments:

[0106] 1. Experimental Methods

[0107] In this experiment, an animal model of psoriasis was induced by imiquimod, and the Chinese medicine composition ointment prepared in Example 2 was administered for intervention. The mechanism of action of the Chinese medicine composition in intervening psoriasis was studied by H&E staining, immunohistochemistry, protein immunoblotting (WB), real-time fluorescence quantitative PCR (RT-qPCR), Elisa, etc.

[0108] 1. Drugs and reagents: 5% imiquimod ointment (for modeling), simple sesame oil + beeswax base prepared in the same steps as in Test Example 2 (administration to the sesame oil-based group), and the Chinese medicine composition ointment prepared in Example 2 (administration to the experimental group).

[0109] 2. Experimental grouping: SPF-grade C57BL / 6 mice were fed adaptively for one week and then randomly divided into 4 groups according to body weight, with 3 mice in each group, namely normal group (Blank), imiquimod group (IMQ group), sesame oil-based group (IMQ+SO group), and experimental group (IMQ+ZQG group).

[0110] 3. Modeling and drug administration: Shave the hair on the back of the mice 24 hours before the start of the experiment to ensure that the back skin is not damaged.

[0111] In the normal group, 62.5 mg of sesame oil base (sesame oil + beeswax) was evenly applied to the back skin and bilateral ear skin of mice, and the drug was administered once a day for 7 consecutive days.

[0112] 62.5 mg of 5% IMQ cream was evenly applied to the back and ears of mice in the imiquimod group once a day for 7 consecutive days.

[0113] 62.5 mg of 5% IMQ cream was evenly applied to the back and ears of mice in the sesame oil-based group. After an interval of 3 hours, 100 mg of sesame oil-based cream was applied once a day for 7 consecutive days.

[0114] 62.5 mg of 5% IMQ cream was evenly applied to the back and ears of mice in the experimental group. After an interval of 3 hours, 100 mg of the Chinese medicine composition ointment was applied once a day for 7 consecutive days. During this period, the ear thickness and back PASI scores of the mice were recorded daily.

[0115] All mice were killed on the 8th day and samples were collected. Part of the skin sample was fixed in 4% paraformaldehyde and embedded in paraffin for tissue morphology analysis or immunohistochemistry analysis. The other part of the skin tissue was frozen in a -80℃ refrigerator to be used as a sample for related experiments. After the mouse eyeball blood was allowed to stand for 30 minutes, it was centrifuged at 3000rmp for 10 minutes, and the supernatant was taken and centrifuged again to obtain mouse serum.

[0116] 4. Index detection: ①HE staining: After formaldehyde fixation, embedding and preparing paraffin sections, after dewaxing, staining, dehydration and sealing, use OLYMPUS SLIDEVIEW VS200 and OlyVIA 3.2.1 software to scan and save the pictures. Epidermal thickness was measured using OlyVIA 3.2.1 software. ②Immunohistochemistry detection: paraffin sections were dewaxed, antigen repaired, blocked, primary antibody incubated, secondary antibody incubated, DAB color developed, hematoxylin stained, and sealed. The observation method was the same as ①. ③WB: After extracting total protein from skin tissue, the protein concentration was determined by the BCA method, the sample loading amount was calculated, and ECL luminescent agent was used for development after electrophoresis, transfer, blocking, primary antibody incubation, and secondary antibody incubation. GAPDH was selected as the internal reference. Bio-Rad Quantity One image analysis software was used for scanning and ImageJ image processing software was used for analysis. ④RT-qPCR: Mouse skin RNA was extracted by Trizol method, and 2-ΔΔCT method was used for calculation and statistical analysis after reverse transcription and amplification. GAPDH was selected as the internal reference, and the primer sequences are shown in Table 3. ⑤ Elisa: Dilute the sample according to the recommended concentration, add it to the ELISA plate (100ul / well) for incubation, and use an ELISA reader to detect the OD value (450nm) after incubation with the primary antibody, secondary antibody, substrate solution, and stop solution, and finally calculate the sample concentration.

[0117] Table 3 Mouse primer sequences

[0118]

[0119] 2. Experimental Results

[0120] 1. Overall, the back PASI score, ear thickness and epidermal thickness of mice in the imiquimod group were higher than those in the normal group, and the differences were statistically significant (P<0.01, Figure 3 AF), proving that the model was successful; at the same time, the back PASI score, ear thickness and epidermal thickness of the experimental group were lower than those of the sesame oil-based group (P<0.01, Figure 3 AF), proving that the efficacy of the Chinese medicine composition ointment on psoriasis is better than that of the sesame oil-based group. In addition, compared with the sesame oil-based group, the changes in the back PASI score and ear thickness of mice treated with the Chinese medicine composition ointment were lower, and the PASI score decreased earlier (P<0.01, Figure 3 AD). HE staining results showed that compared with the sesame oil-based group, the epidermal thickness of mice treated with the Chinese medicine composition ointment was significantly reduced, the spinous process was elongated, and the dermal papillae were improved (P<0.0001, Figure 3 EF).

[0121] Next, we used Elisa experiments to measure the expression of inflammatory factors in mouse serum, among which IL-17A and TNF-α are pro-inflammatory factors, and IL-10 is an anti-inflammatory factor. The results showed that the IL-17A and TNF-α in the imiquimod group and the sesame oil-based group were higher than those in the normal group and the experimental group, respectively. At the same time, the expression of IL-10 in the two groups was lower than that in the normal group and the experimental group, respectively, and the difference was statistically significant (P<0.05, Figure 4 AC).

[0122] At the same time, we also compared the appearance and weight of the five internal organs of the four groups of mice ( Figure 4 D), there were no significant differences in the heart, liver, lung, and kidney of the four groups of mice, but the spleen size of the mice in the imiquimod group and sesame oil group was larger than that of the normal group and the experimental group, and the weight difference was also statistically significant (P<0.01, Figure 4 EF), indicating that the Chinese medicine composition ointment is superior to sesame oil-based in relieving spleen enlargement.

[0123] 2. We selected key proteins in the PI3K / Akt / mTORC1 signaling pathway to verify its therapeutic mechanism. First, the immunohistochemical results showed that the four groups of mice had differences in the protein expression of PI3K, Akt, p-Akt and mTORC1, and the differences were concentrated in the epidermis ( Figure 5 AB). Among them, the expression differences of p-Akt and mTORC1 were the most obvious. WB also obtained similar results ( Figure 5 CD). RT-qPCR results showed that the relative mRNA expressions of mTORC1, Akt1, and PI3K in the imiquimod group and sesame oil group were higher than those in the normal group and the experimental group, respectively (P<0.05, Figure 5 E).

[0124] The above description of the embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating psoriasis, characterized in that: The invention comprises at least two components in the following weight parts: 3-6 parts of lithospermum officinale, 2-5 parts of scutellaria baicalensis, 2-4 parts of bitter almond, 1-2 parts of rhubarb and 1-2 parts of liquorice.

2. A Chinese medicine composition for treating psoriasis according to claim 1, characterized in that: The traditional Chinese medicine composition comprises the following components in parts by weight: 5 parts of lithospermum officinale, 3 parts of scutellaria baicalensis, 3 parts of bitter almonds, 1 part of rhubarb and 1 part of liquorice.

3. A Chinese medicine composition for treating psoriasis according to claim 1, characterized in that: The lithospermum officinale is the dried root of the plants of the Boraginaceae family, lithospermum officinale from Xinjiang or lithospermum officinale from Inner Mongolia.

4. A Chinese medicine composition for treating psoriasis according to claim 1, characterized in that: The scutellaria baicalensis is the dried root of the scutellaria baicalensis plant of the Labiatae family.

5. A Chinese medicine composition for treating psoriasis according to claim 1, characterized in that: The bitter almonds are the dried mature seeds of the Rosaceae plant Prunus armeniaca.

6. A Chinese medicine composition for treating psoriasis according to claim 1, characterized in that: The rhubarb is the dried root and rhizome of medicinal rhubarb.

7. A Chinese medicine composition for treating psoriasis according to claim 1, characterized in that: The licorice is the dried root and rhizome of the leguminous plant licorice.

8. A Chinese medicine composition for treating psoriasis according to claim 1, characterized in that: The Chinese medicine composition is composed of the following components in parts by weight: 5 parts of lithospermum officinale, 3 parts of scutellaria baicalensis, 3 parts of bitter almonds, 1 part of rhubarb and 1 part of liquorice; in: The lithospermum is the dried root of the plant lithospermum xinjiang or lithospermum nemeronggensis of the Boraginaceae family; The scutellaria baicalensis is the dried root of the scutellaria baicalensis plant of the Labiatae family; The bitter almonds are the dried mature seeds of the Rosaceae plant Prunus armeniaca. The rhubarb is the dried root and rhizome of medicinal rhubarb; The licorice is the dried root and rhizome of the leguminous plant licorice.

9. Use of the traditional Chinese medicine composition for treating psoriasis according to any one of claims 1 to 8 in preparing a preparation for treating psoriasis.

10. The use of a traditional Chinese medicine composition for treating psoriasis according to claim 9, characterized in that: The dosage form of the preparation is an external ointment.

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