A traditional Chinese medicine composition for treating psoriasis and its preparation method and application

Abstract

The present invention relates to a traditional Chinese medicine composition for treating psoriasis, and its preparation method and use. The traditional Chinese medicine composition is prepared from the following raw materials: Portulaca oleracea, Sophora flavescens, Dictamni bark, Honeysuckle, Kochia scoparia, Phellodendron amurense, Platycladus orientalis leaves, Paeonia lactiflora, and Lithospermum officinale. The traditional Chinese medicine composition of the present invention has a scientific and reasonable formulation, synergistic efficacy, a small number of ingredients, and controlled quality. The combination of monarch, minister, adjuvant, and envoy in the present invention's formulation is scientific and reasonable. The combination of anti-inflammatory and immunomodulatory heat-clearing, blood-cooling, and antipruritic drugs can effectively eliminate the cause of the disease and enhance the antipruritic effect, exerting anti-inflammatory, antiproliferative, and local vasoconstrictive effects, with the advantages of increased efficacy and reduced toxicity, and can reduce the risk of recurrence. This promotes epithelial tissue repair, maintains the dynamic balance of skin keratinization, effectively prevents the recurrence of psoriasis, and reduces the suffering of patients.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine compositions, and specifically relates to a traditional Chinese medicine composition for treating psoriasis and a pharmaceutical preparation thereof, a method for preparing the pharmaceutical preparation, and the use of the traditional Chinese medicine composition and the pharmaceutical preparation in preparing a medicine for treating autoimmune skin diseases. Background Art

[0002] Psoriasis is a common chronic inflammatory skin disease characterized by localized or widespread scaly erythema or plaques. In addition to skin and nail lesions, psoriasis patients often experience joint symptoms and even irreversible joint deformities. Patients with moderate to severe psoriasis often suffer from comorbidities such as obesity, hypertension, Crohn's disease, metabolic syndrome, and depression, which severely impact their quality of life. In recent years, the incidence and prevalence of psoriasis have been increasing year by year. Current Western medical treatment options primarily include topical medications, phototherapy, systemic medications, and biologics. While standardized treatments can effectively alleviate symptoms, psoriasis cannot currently be completely cured and is prone to relapse, requiring long-term systemic treatment. Due to the various adverse reactions, high costs, and recurring symptoms of long-term systemic treatment, patients often experience poor treatment satisfaction and low compliance. Consequently, an increasing number of psoriasis patients are turning to complementary and alternative medicine.

[0003] Traditional Chinese medicine (TCM) is an integral part of complementary and alternative medicine and has a long history in the treatment of psoriasis. Based on the principles of integrated diagnosis and treatment, syndrome differentiation, holistic approach, and stage-based treatment, TCM can provide personalized treatment plans for psoriasis patients, offering advantages unmatched by other therapies. Furthermore, growing evidence suggests that TCM can improve patients' clinical symptoms, reduce Psoriasis Area and Severity Index scores, mitigate the side effects of Western medications, delay psoriasis recurrence, and improve quality of life.

[0004] Chinese patent CN114272339 discloses a traditional Chinese medicine composition for treating eczema, skin allergies or psoriasis and its preparation method. The traditional Chinese medicine composition contains 20 components, which are numerous and complex, making quality control difficult and not conducive to production. Moreover, the research is also superficial in efficacy and does not involve the mechanism of action of the drug, so it cannot ensure whether recurrence will occur.

[0005] Chinese patent CN116850236 discloses a topical Chinese medicine composition for the treatment of psoriasis, its formulation, and its use. Based on its mechanism of action, the composition suppresses the expression of inflammatory factors such as IL-1β, IL-6, IL-8, IL-17A, IL-22, and IL-23, alleviating skin lesions in psoriatic mice and improving inflammation and autoimmune responses. However, the composition contains the root of the genus Torchwort, which has significant side effects, including suppressive effects on the gonads and bone marrow, making it unsuitable for long-term use.

[0006] In summary, there is still a lack of Chinese herbal compositions and preparations in the field of psoriasis treatment that have good efficacy, avoid recurrence, have controllable quality, and are free of toxic side effects. Summary of the Invention

[0007] The present invention provides a Chinese medicine composition for treating psoriasis, a preparation method and an application thereof, and aims to provide a Chinese medicine composition and a preparation thereof that are still lacking in the field of treating psoriasis and have good efficacy, avoid recurrence, controllable quality and no toxic side effects.

[0008] Technical solution:

[0009] The first aspect of the present invention provides a traditional Chinese medicine composition for treating psoriasis, which is prepared from the following raw materials: purslane, sophora flavescens, Dictamni bark, honeysuckle, Kochia scoparia, Phellodendron amurense, Platycladus orientalis leaves, red peony root, and lithospermum officinale.

[0010] Furthermore, the Chinese medicine composition is made from the following raw materials in parts by weight: 1-300 parts of purslane, 1-300 parts of sophora flavescens, 1-300 parts of dittany bark, 1-300 parts of honeysuckle, 1-300 parts of kochia scoparia, 1-300 parts of phellodendron amurense, 1-300 parts of orientalis leaves, 1-200 parts of red peony root, and 1-200 parts of lithospermum officinale.

[0011] Preferably, the Chinese medicine composition is made from the following raw materials in parts by weight: 20-200 parts of Portulaca oleracea, 20-200 parts of Sophora flavescens, 20-200 parts of Dictamni cortex, 20-200 parts of Honeysuckle, 20-200 parts of Kochia scoparia, 20-200 parts of Phellodendron amurense, 20-200 parts of Platycladus orientalis leaves, 20-100 parts of Paeonia lactiflora, and 20-100 parts of Lithospermum officinale.

[0012] The second aspect of the present invention provides a pharmaceutical preparation for treating psoriasis, which is composed of an active ingredient and excipients, wherein the active ingredient is the traditional Chinese medicine composition.

[0013] Preferably, the pharmaceutical preparation is any one of a bath, a cream, a liniment, a lotion, a spray, a gel, an ointment and an oil.

[0014] Preferably, the cream is prepared by the following process:

[0015] 1) Weighing purslane, sophora flavescens, Dictamni bark, honeysuckle, Kochia scoparia, Phellodendron amurense, Platycladus orientalis leaves, Paeonia lactiflora, and Lithospermum officinale in proportion to weight, soaking the mixed drugs in cold water for 1 hour, and then decocting them 2 to 3 times, adding 8 to 12 times the amount of water (mass to volume ratio g / mL) each time, and decocting them for 1 to 5 hours each time; collecting the filtrate after decoction and concentrating the filtrate to 600 to 800 mL by a normal pressure heating and concentration method to obtain a traditional Chinese medicine extract, and mixing the traditional Chinese medicine extract with an aqueous phase additive to form an aqueous phase component; the aqueous phase additive includes one or more existing additives such as an aqueous phase solvent, an aqueous phase emulsifier, a humectant, and a preservative, and the specific additives can be obtained through limited experiments according to actual needs.

[0016] 2) Weigh the oil phase component and heat it in an 80°C water bath until melted; weigh the water phase component and heat it to above 80°C; after the oil phase is completely melted, pour the water phase into the oil phase and stir rapidly until uniformly mixed. Homogenize for 5 minutes, then continue stirring with a glass rod until the paste cools and solidifies to obtain a cream; the mass ratio of the oil phase to the water phase must be such that each gram of the resulting cream contains 0.7-0.9 g of the active ingredient.

[0017] Preferably, the oil phase includes one or more of an oil phase emulsifier, a penetration enhancer, a lubricant, and a fatty alcohol. Specific amounts can be obtained through limited experiments according to actual needs.

[0018] Preferably, the oil phase emulsifier includes stearic acid, Span-60 and Tween-80, and the mass ratio of the three is 5-7:0.2-0.4:2.0-2.3.

[0019] The third aspect of the present invention provides a use of the traditional Chinese medicine composition or the pharmaceutical preparation in preparing a drug for treating psoriasis.

[0020] Furthermore, the Chinese medicine composition or pharmaceutical preparation inhibits the onset of psoriasis through the JAK3 / STAT3 signaling pathway.

[0021] (3) Beneficial effects

[0022] The present invention provides a Chinese medicine composition for treating psoriasis, a pharmaceutical preparation of the Chinese medicine composition, a method for preparing the pharmaceutical preparation, and the use of the Chinese medicine composition or pharmaceutical preparation in preparing a medicament for treating autoimmune skin diseases. The Chinese medicine composition of the present invention has a scientific and reasonable formulation, synergistic synergy, a small number of ingredients, and controllable quality. It consists of only 9 Chinese herbs, and the formulation is simple, overcoming the shortcomings of the current Chinese patent medicines for treating psoriasis, which are complex in formulation and difficult in quality control. The present invention proposes using Sophora flavescens, Dictamni cortex, and Portulaca oleracea as monarch herbs, supplemented by anti-inflammatory, blood-cooling, blood-activating, and antipruritic Chinese herbs, using Honeysuckle, Kochia scoparia, and Phellodendron amurense as minister herbs, using Platycladus orientalis leaves as adjuvant herbs, and using Paeonia lactiflora and Lithospermum officinale as guiding herbs. The monarch, minister, adjuvant, and guiding herbs in the formulation are scientific and reasonable, and the combination of anti-inflammatory, immunomodulatory, heat-clearing, blood-cooling, and antipruritic herbs can effectively eliminate the cause of the disease and enhance the antipruritic effect, exerting anti-inflammatory, antiproliferative, and local vasoconstrictive effects, with the advantages of increasing efficacy and reducing toxicity, and can reduce the risk of recurrence. This can promote epithelial tissue repair, maintain the dynamic balance of skin keratinization, effectively prevent the recurrence of psoriasis, and reduce the suffering of patients. It overcomes the shortcomings of Western medicine, such as single target, many restrictions on combined medication, and large toxic side effects of some drugs.

[0023] Both mouse and clinical trials have demonstrated that the proposed Chinese herbal composition and pharmaceutical preparation are highly effective in treating psoriasis, with virtually no recurrence and no toxic side effects, making them suitable for widespread use. In particular, the compound ginseng flower cream exhibits excellent efficacy, controlled quality, portability, ease of storage, few side effects, abundant resources, and low price, potentially addressing the current high cost of medical care. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is the appearance of skin lesions on the back of mice;

[0025] Figure 2 PASI scores for the back skin lesions of mice in each group (Note: Compared with the blank group, ### P < 0.001; compared with the model group, ***P < 0.001, *P < 0.05);

[0026] Figure 3 The thickness of the epidermis of mice in each group (compared with the blank group, ### P < 0.001; compared with the model group, ***P < 0.001, **P < 0.01);

[0027] Figure 4 HE staining of skin lesions of mice in each group (300×);

[0028] Figure 5 The positive expression of STAT3 in the back lesions of mice in each group (compared with the blank group, ### P<0.001; compared with the model group, ***P<0.001, **P<0.01, *P<0.05; compared with the high-dose compound ginseng flower group,△△△ P < 0.001, △△ P < 0.01);

[0029] Figure 6 The positive expression of P-STAT3 in the back lesions of mice in each group (compared with the blank group, ### P<0.001; compared with the model group, ***P<0.001, **P<0.01; compared with the high-dose compound ginseng flower group, △△△ P < 0.001);

[0030] Figure 7 The positive expression of P-JAK3 in the back lesions of mice in each group (compared with the blank group, ### P<0.001; compared with the model group, ***P<0.001, *P<0.05; compared with the high-dose compound ginseng flower group, △△△ P<0.001, △△ P < 0.01);

[0031] Figure 8 Comparison of the expression levels of IL-6, IL-1β and TNF-α in the serum of mice in each group (compared with the blank group, ### P < 0.001, ## P < 0.01; compared with the model group, **P < 0.01, *P < 0.05);

[0032] Figure 9 Comparison of IL-17A, JAK3, and STAT3 mRNA expression levels in skin lesions of mice in each group (compared with the blank group, ## P<0.01, # P < 0.05; compared with the model group, **P < 0.01, *P < 0.05). DETAILED DESCRIPTION

[0033] To further illustrate the technical means and effects of the present invention, the present invention is further described below with reference to the embodiments and drawings. It should be understood that the specific embodiments described herein are only used to explain the present invention, rather than to limit the present invention.

[0034] Psoriasis is a chronic, recurrent, inflammatory, systemic immune-mediated disease induced by the interaction between the individual and the environment. The core mechanism of psoriasis pathogenesis is the excessive proliferation and abnormal differentiation of epidermal keratinocytes (KCs) due to immune pathways involving interleukin-23 (IL-23) and T helper 17 (Th17) cells. Multiple cells, including T cells, dendritic cells, neutrophils, and keratinocytes, induce characteristic changes in psoriasis, including neutrophil infiltration and angiogenesis, through cytokines such as tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), IL-17, and IL-22. The JAK-STAT signaling pathway is a common enzyme-linked receptor-mediated signaling pathway, in which signal transducer and activator of transcription 3 (STAT3) is an important transcription factor that participates in multiple stages of psoriasis pathogenesis by transmitting signals from multiple cytokines, including IL-12, IL-23, IL-22, and TNF-α. The JAK3 / STAT3 signaling pathway plays a key role in the innate immunity, adaptive immunity, and excessive proliferation and abnormal differentiation of keratinocytes in the pathogenesis of psoriasis. Among them, the partial overactivation of the adaptive immune system is considered to be the central link in the pathogenesis of psoriasis.

[0035] This invention proposes a traditional Chinese medicine composition (compound ginseng flower preparation) for treating psoriasis. It downregulates genes encoding proinflammatory cytokines to exert anti-inflammatory, immunosuppressive, antiproliferative, and local vasoconstrictive effects, reducing the risk of relapse. It is made from the following ingredients: Portulaca oleracea, Sophora flavescens, Dictamni bark, Honeysuckle, Kochia scoparia fruit, Phellodendron amurense, Platycladus orientalis leaves, Paeonia lactiflora, and Lithospermum officinale.

[0036] The effects of each medicine are as follows:

[0037] Purslane - enters the Heart, Liver, Spleen, and Large Intestine meridians; Benefits: Clears heat and detoxifies, cools blood and stops bleeding, is anti-inflammatory, immunomodulatory, and antioxidant. It can relieve itching and improve skin symptoms such as erythema and scaling.

[0038] Sophora flavescens - enters the Liver, Kidney, Large Intestine, Small Intestine, Bladder, and Heart meridians; Efficacy: clears heat and dampness, dispels wind and kills insects, regulates immunity, detoxifies and fights inflammation;

[0039] Dictamni peel – enters the spleen, stomach, and bladder meridians; benefits: clearing heat and dampness, dispelling wind and detoxifying, and immune regulation. It can inhibit oxidative stress-induced cell senescence. Dictamni peel is rich in flavonoids, which have anti-inflammatory effects.

[0040] Honeysuckle - enters the lung meridian, heart meridian, and stomach meridian; effects: clearing heat and detoxifying, anti-inflammatory, tonifying deficiency and treating wind;

[0041] Kochia scoparia seeds – enter the kidney and bladder meridians; benefits: clears heat and dampness, dispels wind and relieves itching. Kochia scoparia seeds and its main saponin momordica charantia can prevent inflammation.

[0042] Huang Bai - enters the kidney and bladder meridians; effects: clearing heat and dampness, purging fire and detoxifying, anti-inflammatory, and immune regulation;

[0043] Platycladus orientalis leaves - enter the lung meridian, liver meridian, and large intestine meridian; effects: stabilize the immune system, kill bacteria, cool blood and stop bleeding, dispel rheumatism, disperse swelling and toxins, antioxidant, anti-inflammatory, and immune regulation;

[0044] Red Peony Root - enters the Liver Meridian; Efficacy: clears heat and cools blood, promotes blood circulation and removes blood stasis, anti-inflammatory, antioxidant, and immune regulation;

[0045] Lithospermum officinale - enters the heart, pericardium and liver meridians; Efficacy: cooling blood, promoting blood circulation, detoxifying and clearing rashes, antibacterial, anti-inflammatory, and antioxidant; shikonin can inhibit the proliferation of keratinocytes and promote apoptosis.

[0046] Pharmacological analysis:

[0047] The present invention proposes using Sophora flavescens, Dictamni cortex, and Portulaca oleracea, which have heat-clearing and detoxifying, anti-inflammatory, and immunomodulatory effects, as the main medicinal herbs, supplemented by anti-inflammatory, blood-cooling, blood-activating, and antipruritic Chinese medicines, with honeysuckle, Kochia scoparia, and Phellodendron chinense as ministerial herbs, Platycladus orientalis leaves as adjuvants, and Paeonia lactiflora and Lithospermum officinale as guiding herbs. Among them, the main medicinal herbs Sophora flavescens, Dictamni cortex, and Portulaca oleracea have anti-inflammatory and immunomodulatory effects; they can inhibit JAK and STAT3 expression by reducing the levels of inflammatory factors such as TNF-α, IFN-γ, IL-6, and IL-8, and increasing SOCS1 expression, thereby hindering the activation of the JAK / STAT3 signaling pathway, thereby inhibiting KC proliferation and regulating T lymphocyte activation and balance. The ministerial herbs Honeysuckle, Kochia scoparia, and Phellodendron chinense are all traditional Chinese medicines with heat-clearing and detoxifying, anti-inflammatory, and antipruritic effects, and can assist the main medicinal herbs in exerting their anti-inflammatory and immunomodulatory effects, as well as their antipruritic effects. The adjuvant drugs Platycladus orientalis, Paeonia lactiflora and Lithospermum officinale are all traditional Chinese medicines with cooling blood, anti-inflammatory and immunomodulatory effects. They can also assist the main drug in exerting anti-inflammatory and immunomodulatory effects, as well as cooling blood and killing bacteria, thereby inhibiting the proliferation of keratinocytes and promoting apoptosis.

[0048] The above-mentioned combination of monarch, minister, assistant, and envoy herbs is scientifically sound. The combination of anti-inflammatory and immunomodulatory herbs with heat-clearing, cooling, and antipruritic agents effectively eliminates the cause and enhances its antipruritic properties. They exert anti-inflammatory, antiproliferative, and local vasoconstrictive effects, offering the advantages of increased efficacy and reduced toxicity, thus reducing the risk of relapse. This promotes epithelial tissue repair, maintains the dynamic balance of skin keratinization, effectively prevents recurrence of psoriasis, and alleviates patient suffering.

[0049] Example 1

[0050] Traditional Chinese medicine bathing, guided by TCM syndrome differentiation and treatment, involves bathing the patient's entire body and surrounding areas with a decoction of Chinese herbs, allowing the drugs to be directly absorbed through the skin and exert their effects. A compound herbal preparation containing Portulaca oleracea, Sophora flavescens, Dictamni bark, Lonicera japonica, Kochia scoparia, Phellodendron amurense, Platycladus orientalis leaves, Paeonia lactiflora, and Lithospermum officinale is used. Based on the dosages specified in the Pharmacopoeia of the People's Republic of China (2010 edition), a 30g decoction of each herb is diluted in a 1:1 ratio (mass to volume ratio g / L) with warm water, followed by a 20-minute bath. Heat in the skin dilates blood vessels, allowing the Chinese herbs to be directly absorbed through the skin and other areas, exerting their effects on the lesions. This treatment can soften and clear psoriasis lesions, shorten treatment duration, reduce the incidence of adverse reactions, and significantly improve the quality of life of psoriasis patients.

[0051] Example 2

[0052] Dosage forms for topical application to the skin can be categorized into various types, including baths, creams, liniments, lotions, sprays, gels, pastes, patches, skin patches, ointments, and oils. This example uses a cream as an example. Cream formulations are promising drug carriers for transdermal drug delivery. A cream is a semisolid emulsion containing one or more dissolved or dispersed active substances and can be defined as a two-phase system in which the dispersed phase, or internal phase, is finely and uniformly dispersed in the continuous phase, or external phase. Depending on the nature of the dispersed phase, either an oil-in-water (o / w) or water-in-oil (w / o) cream can be obtained. After optimization and screening experiments in this embodiment, the aqueous phase components include a traditional Chinese medicine extract and glycerol, and the mass ratio of the two is 250-280:48-55. In this embodiment, the aqueous phase is 250-280 g of the traditional Chinese medicine extract and 48-55 g of glycerol; the oil phase includes stearic acid, glyceryl monostearate, white petrolatum, liquid paraffin, Span-60, Tween-80 and ethyl paraffin, and the mass ratio is 56-65:20-25:35-45:35-45:3-4:15-20:0.1-1.2. In this embodiment, the oil phase is 56-65 g of stearic acid, 20-25 g of glyceryl monostearate, 35-45 g of white petrolatum, 35-45 g of liquid paraffin, 3-4 g of Span-60, 15-20 g of Tween-80, and 0.1-1.2 g of ethyl paraffin. Each gram of cream contains 0.7 to 0.9 grams of active ingredient. The compound ginseng flower cream obtained under these conditions has a fine texture, is refreshing and easy to spread, has a pleasant odor, and is brown in color. It meets product appearance and sensory evaluation requirements, has good stability, and is easy to use.

[0053] The present invention does not limit the specific components and addition amounts of the water phase and the oil phase. The specific components and addition amounts of the water phase and the oil phase can be obtained by those skilled in the art through a limited number of screening experiments based on actual needs, as long as they can meet the appearance and sensory evaluation of the product.

[0054] Preparation method:

[0055] 1) Preparation of Chinese medicine extract:

[0056] Weigh 200g each of Portulaca oleracea, Sophora flavescens, Dictamni bark, Flos Lonicerae, Fructus Kochiae, Cortex Phellodendri, and Folium Platycladi, 70g each of Radix Paeoniae Rubra and Radix Lithospermi, put the medicine (total 1540g) into a decoction bag, soak in cold water for 1 hour and decoct twice, add 10 times of amount (15.4L) water each time, and decoct for 2 hours each time. Collect the filtrate after two decoctions and place it in a container. The filtrate is concentrated to 800ml of Chinese medicine extract by the method of normal pressure heating concentration. Take 280g of Chinese medicine extract and 55g of glycerol as aqueous phase. 2) Preparation of Compound Ginseng Flower Cream:

[0057] For an O / W formulation, weigh the oil phase components (56g of stearic acid, 20g of glyceryl monostearate, 35g of white petrolatum, 35g of liquid paraffin, 3g of Span-60, 15g of Tween-80, and 0.1g of ethylparaben) and heat them in an 80°C water bath until melted. Heat the aqueous phase to above 80°C. Once the oil phase is completely melted, pour the aqueous phase into the oil phase and rapidly stir until uniformly mixed. Homogenize using a high-speed homogenizer for 5 minutes, then continue stirring with a glass rod until the paste cools and solidifies. This results in a compound ginseng flower cream containing 0.78g of active ingredient per 1g of the resulting cream.

[0058] Example 3

[0059] 1) Preparation of Chinese medicine extract:

[0060] Take 100g each of Herba Portulacae, Radix Sophorae Flavescentis, Cortex Dictamni, Flos Lonicerae, Fructus Kochiae, Cortex Phellodendri, Leaf of Platycladus orientalis, 50g each of Radix Paeoniae Rubra and Radix Arnebiae (Radix Lithospermi), put medicine (totally 800g) into medicine-decocting bag, decoct twice after cold water soaking for 1 hour, add 10 times of amount (8L) water at each time, decoct 2 hours at each time.Collect the filtrate after twice decocting and insert in container, adopt the method for normal pressure heating concentration that filtrate is concentrated into the Chinese medicine extract of 600ml.Get Chinese medicine extract 250g, glycerol 48g is as aqueous phase.

[0061] 2) Preparation of compound ginseng flower cream:

[0062] For an O / W formulation, weigh the oil phase components (60g of stearic acid, 22g of glyceryl monostearate, 40g of white petrolatum, 40g of liquid paraffin, 3g of Span-60, 17g of Tween-80, and 0.3g of ethylparaben) and heat them in an 80°C water bath until melted. Heat the aqueous phase to above 80°C. Once the oil phase is completely melted, pour the aqueous phase into the oil phase and rapidly stir until uniformly mixed. Homogenize using a high-speed homogenizer for 5 minutes, then continue stirring with a glass rod until the paste cools and solidifies. This results in a compound ginseng flower cream containing 0.75g of active ingredient per 1g of the resulting cream.

[0063] Example 4

[0064] 1) Preparation of Chinese medicine extract:

[0065] Weigh 300g each of Portulaca oleracea, Sophora flavescens, Dictamni bark, Flos Lonicerae, Fructus Kochiae, Cortex Phellodendri, and Leaf of Platycladus orientalis, 120g each of Radix Paeoniae Rubra and Radix Lithospermi, put the medicine (total 2340g) into a decoction bag, soak in cold water for 1 hour and decoct twice, add 10 times of amount (23.4L) water each time, and decoct for 2 hours each time. Collect the filtrate after twice decoction and place it in a container, and adopt the method for normal pressure heating concentration to concentrate the filtrate to the Chinese medicine extract of 800ml. Take 260g of Chinese medicine extract and 50g of glycerol as aqueous phase. 2) Preparation of Compound Ginseng Flower Cream:

[0066] For an O / W formulation, weigh the oil phase components (65g of stearic acid, 25g of glyceryl monostearate, 45g of white petrolatum, 45g of liquid paraffin, 4g of Span-60, 18g of Tween-80, and 1.0g of ethylparaben) and heat them in an 80°C water bath until melted. Heat the aqueous phase to above 80°C. Once the oil phase is completely melted, pour the aqueous phase into the oil phase and rapidly stir until uniformly mixed. Homogenize using a high-speed homogenizer for 5 minutes, then continue stirring with a glass rod until the paste cools and solidifies. This results in a compound ginseng flower cream containing 0.88g of active ingredient per 1g of the resulting cream.

[0067] Comparative Example 1

[0068] The difference from Example 2 is that the monarch drug Portulaca oleracea is missing.

[0069] Comparative Example 2

[0070] The difference from Example 2 is that the main medicine does not contain Portulaca oleracea, but is replaced by 200g of Poria cocos with the same efficacy.

[0071] Comparative Example 3

[0072] The difference from Example 2 is that it does not contain Platycladus orientalis leaves and Paeonia lactiflora.

[0073] The beneficial effects of the present invention are demonstrated as follows:

[0074] (I) Study on the efficacy of compound ginseng flower cream on imiquimod-induced psoriasis mice

[0075] 1. Experimental Materials

[0076] 1.1 Experimental Animals

[0077] SPF grade 6-8 week old BALB / c male mice weighing (20±2) g were purchased from Beijing Huafukang Biotechnology Co., Ltd.

[0078] 1.2 Experimental drugs

[0079] White vaseline; Imiquimod cream; Calcipotriol cream; low, medium and high doses of compound ginseng flower cream (Example 2); Comparative Examples 1 to 3.

[0080] 2. Experimental Methods

[0081] 2.1 Construction of Imiquimod Cream-Induced Psoriasis Mouse Model and Administration

[0082] Fifty-four 6-8 week old BALB / c male mice were randomly divided into a blank group (CON), a model group (IMQ), a low-dose (61%) compound ginseng flower cream group (IMQ+SH+L), a medium-dose (68%) compound ginseng flower cream group (IMQ+SH+M), a high-dose (76%) compound ginseng flower cream group (IMQ+SH+H), comparative examples 1-3 (IMQ+D1-D3) (high dose), and a calcipotriol group (CAL), with 6 mice in each group. Except for the blank group, which was given an equal amount of white vaseline, the mice in the other groups were given 5% imiquimod cream 62.5 mg once a day at 8:00 am for 7 consecutive days to establish the model. At the same time as the model establishment, the mice in the low, medium, and high doses of compound ginseng flower cream groups, comparative examples 1-3, and calcipotriol cream groups were given once a day at 2:00 pm. 24 hours after the last administration, the mice were anesthetized with pentobarbital and then killed by cervical dislocation. The skin lesions of the mice were photographed and samples were collected.

[0083] 2.2 Psoriasis Lesion Area and Disease Severity (PASI) Scoring in Mice

[0084] The skin lesions of mice were scored 24 hours after the last administration using the Psoriatic Arthritis Injury Area and Severity (PASI) score, which includes erythema, scaling, and thickening, with each item scored from 0 to 4 points: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe. The PASI score was obtained by adding up the three scores.

[0085] 2.3 HE staining

[0086] The skin samples were fixed in 4% paraformaldehyde for 24 hours, then dehydrated, waxed, embedded, cooled, and sliced ​​into pathological white slides, which were then stained with hematoxylin and eosin. Finally, images were collected and observed, and epidermal thickness was measured.

[0087] 2.4 Observation of STAT3, P-STAT3, and P-JAK3 positive expressions by immunohistochemistry (IHC) staining

[0088] The mouse skin lesion tissue was fixed, paraffin-embedded, sectioned, dewaxed, hydrated, antigen retrieved, serum blocked, incubated with primary and secondary antibodies, developed with DAB, counterstained with hematoxylin, dehydrated, and mounted with neutral gum.

[0089] Under the microscope, the positive staining area was observed to be brownish yellow. The images were collected and analyzed, and three fields of view were randomly selected. The optical density of the photos was quantitatively analyzed using Image J software to calculate the positive cumulative optical density (IOD).

[0090] 2.5 Determination of IL-6, IL-1β, and TNF-α expression in mouse serum by enzyme-linked immunosorbent assay (ELISA)

[0091] The mouse eyeballs were removed and about 1.0 ml of peripheral blood was collected. After standing at room temperature for 40 min, the blood was centrifuged at 3000 rpm and 4°C for 10 min. The upper serum was collected in an EP tube and stored in a -80°C refrigerator for later use.

[0092] The ELISA kit was operated according to the instructions of the kit to detect the expression levels of IL-6, IL-1β, and TNF-α in the serum of each group of mice.

[0093] 2.6 Observation of JAK3, STAT3, and IL-17A mRNA expression by real-time fluorescence quantitative PCR (RT-qPCR)

[0094] Total RNA was extracted from mouse skin lesions using the Trizol method, and the total RNA concentration was determined. RNA was reverse transcribed into cDNA according to the reverse transcription kit instructions, and then subjected to real-time fluorescence quantitative polymerase chain reaction. The relative expression levels of JAK3, STAT3, and IL-17A mRNA were calculated using the 2-ΔΔCt method, using 18s as the internal reference gene.

[0095] 2.7 Statistical methods

[0096] Collected data were summarized using Excel and presented as mean ± standard deviation (x ± s). GraphPad Prism 10 software was used for plotting and statistical analysis. Pairwise comparisons of data were performed using the t-test, and intergroup comparisons were performed using one-way analysis of variance. α = 0.05 was used as the test level, and P < 0.05 was considered statistically significant.

[0097] 3. Results

[0098] 3.1PASI score

[0099] The mice in each group were scored 24 hours after the last administration. The results are shown in Tables 1 and Figures 1-2 .

[0100] Table 1 PASI scores of each group

[0101]

[0102] From Table 1 and Figure 2It can be seen that the blank group mice had no erythema, scaling and thickening on their skin, so the PASI score was 0. Compared with the blank group, the PASI score of the model group mice was significantly increased, and the difference was statistically significant; compared with the model group, the PASI score of the compound ginseng flower cream group and the calcipotriol group mice was significantly decreased, and the difference was statistically significant. Compared with the control examples 1 to 3 of the same concentration, the PASI score of the mice in the high-dose compound ginseng flower cream group was lower than that of control examples 1 to 3. This shows that the Chinese medicine composition of the present invention is scientific and reasonable in formulation, synergistic and synergistic, and cannot be obtained by simple replacement. It can exert anti-inflammatory, anti-proliferative and local vasoconstrictive effects, has good efficacy in the treatment of psoriasis, and has no toxic side effects.

[0103] from Figure 1 On day 8, the skin of the mice in the blank group was smooth and delicate, without erythema, scaling, or thickening. Compared with the blank group, the skin of the mice in the model group showed erythema and flaky scaling, accompanied by skin thickening. Compared with the model group, the skin erythema and scaling of the mice in the high-dose compound ginseng flower cream and calcipotriol groups were significantly reduced or even disappeared, and the skin thickening was significantly improved. The skin erythema and scaling of the mice in the low- and medium-dose compound ginseng flower cream control groups 1 to 3 were slightly reduced, and the skin thickening was slightly improved, but the improvement effect was significantly lower than that in the high-dose compound ginseng flower cream group.

[0104] 3.3 Epidermal thickness

[0105] The epidermal thickness of mice in each group was measured. Figure 3 As shown, compared with the blank group, the epidermal thickness of the model group mice was significantly thicker, with a statistically significant difference. Compared with the model group, the epidermal thickness of the mice in the high-dose compound ginseng flower cream group and the calcipotriol group was thinner, with a statistically significant difference. The high-dose compound ginseng flower cream group was superior to the low- and medium-dose compound ginseng flower cream groups, and the epidermal thickness of the mice in the control examples 1 to 3 with the same high dose was less thinning, demonstrating that the Chinese medicine composition of the present invention is scientifically formulated and synergistic.

[0106] 3.4 Histomorphology of mice in each group

[0107] HE staining results showed that Figure 4 As shown (excluding comparative examples 1 to 3 with higher PASI scores), the blank group mice had no hyperkeratosis and parakeratosis on their skin, the epidermis was of normal thickness, and no inflammatory cell infiltration was observed in the superficial dermis. Compared with the blank group, the model group mice had hyperkeratosis with parakeratosis, decreased granular cells, thickened stratum spinosum, epidermal protrusions extending downward in a "club-shaped" pattern, thickened epidermis, and infiltration of lymphocytes and neutrophils in the superficial dermis, consistent with the pathological changes of psoriasis. Compared with the model group, the hyperkeratosis and parakeratosis of mice in the high-dose compound ginseng flower cream group and the calcipotriol group were alleviated, the thickening of the stratum spinosum improved, and the infiltration of inflammatory cells in the superficial dermis was reduced.

[0108] 3.5 Immunohistochemistry results and optical density quantitative analysis results showed:

[0109] like Figure 5-7 As shown in the results, the optical density values ​​of STAT3, P-STAT3, and P-JAK3 in the back lesions of mice in the model group were significantly higher than those in the blank group, and the differences were statistically significant; compared with the model group, the optical density values ​​of STAT3, P-STAT3, and P-JAK3 in the calcipotriol group and each dose group of compound ginseng flower cream were all reduced, among which the high-dose compound ginseng flower cream group and calcipotriol group had the most obvious decreases.

[0110] 3.6 Effect of Compound Ginseng Flower Cream on the Expression of IL-6, IL-1β, and TNF-α in Mouse Serum

[0111] like Figure 8 As shown in the results, compared with the blank group, the levels of IL-6, IL-1β and TNF-α in the serum of the model group were significantly increased; compared with the model group, the levels of IL-6, IL-1β and TNF-α in the serum of the calcipotriol group and the high-dose compound ginseng flower group were decreased.

[0112] 3.7 Effect of compound ginseng flower cream on IL-17A, JAK3, and STAT3 mRNA expression in mouse skin tissue:

[0113] like Figure 9 As shown in the results, compared with the blank group, the expression levels of IL-17A, JAK3, and STAT3 mRNA in the skin lesion tissues of the mice in the model group were significantly increased; compared with the model group, the expression levels of IL-17A, JAK3, and STAT3 mRNA in the skin lesion tissues of the mice in the calcipotriol group and the high-dose compound ginseng flower group were decreased.

[0114] In summary, the compound ginseng flower cream proposed in this invention can alleviate the inflammatory response of IMQ-induced psoriasis lesions in mice and improve psoriasis lesions in mice, with the high-dose group showing the best effect. A high-dose compound ginseng flower cream can effectively alleviate imiquimod-induced psoriasis lesions in mice, reduce epidermal thickness, inhibit keratinocyte proliferation, and reduce lymphocyte infiltration. Compound ginseng flower cream may exert its therapeutic effect on psoriasis by inhibiting the JAK3 / STAT3 signaling pathway and reducing the secretion of proinflammatory cytokines.

[0115] (2) Clinical trials

[0116] 1. Research drugs

[0117] Example 1 (Compound Ginseng Flower Medicinal Bath), Example 2 (Compound Ginseng Flower Cream), Fluticasone Propionate Cream (Zhejiang Xianju) (Control Group).

[0118] 2. Subject recruitment and source

[0119] Patients with psoriasis vulgaris who visited the Department of Dermatology of the Northern Theater Command General Hospital, the Department of Dermatology of the First Affiliated Hospital of China Medical University, and the Dermatology Outpatient Department of Shengjing Hospital of China Medical University.

[0120] 3. Inclusion criteria

[0121] Volunteer to participate in the study and sign the informed consent form. Male or female patients aged 18-65 years. Patients must have a clear clinical diagnosis of psoriasis vulgaris according to the diagnostic criteria for psoriasis vulgaris established by the Journal of Clinical Dermatology. Patients must have moderate to severe psoriasis vulgaris, with a psoriasis body surface area (BSA) ≥ 10% and a Psoriasis Area and Severity Index (PASI) score > 10 and ≤ 20. Patients must not have used systemic or topical glucocorticoids, immunosuppressants, biologics, retinoic acid, or phototherapy within one month prior to enrollment.

[0122] 4. Research treatment options

[0123] The control group was given the medicinal bath treatment of Example 1, decocting 30 g of each of 8 Chinese herbs including Sophora flavescens, Dictamnus chinensis, and Portulaca oleracea in a 1:1 ratio with warm water, and then bathing for 20 min, once a day;

[0124] The cream of Example 2 was applied externally to the affected area only. The drug dosage was one fingertip unit of the subject's cream, evenly applied to 2% of the body surface area, once a day.

[0125] The positive control group received fluticasone propionate cream applied topically only to the affected area. The dosage consisted of one fingertip unit of cream evenly applied to 2% of the body surface area, once daily. Each group received treatment for four weeks, with follow-up for four weeks. During treatment, participants were not allowed to use any other topical treatments, phototherapy, or systemic therapies that might affect psoriasis evaluation.

[0126] 5. Analysis of test results

[0127] 5.1 Clinical efficacy analysis:

[0128] Six groups were observed for clinical efficacy, with the following criteria: (1) efficacy index (lesion improvement rate) = (PASI score before treatment - PASI score after treatment) / PASI score before treatment * 100%; (2) cured: efficacy index ≥ 95%; lesions completely resolved, leaving only a few inactive lesions or pigmentation changes; (3) markedly effective: 95% > efficacy index ≥ 60%; lesions clearly resolved, with significant improvement in symptoms; (4) effective: 60% > efficacy index ≥ 30%; symptoms improved; (5) ineffective: 30% > efficacy index, with no change in symptoms; (6) total effective rate = cure rate + markedly effective rate + effective rate. See Table 2.

[0129] Table 2 Clinical efficacy observation results

[0130]

[0131] *Significantly different from the control group (P<0.05).

[0132] As can be seen from Table 2, after the treatment course, the total effective rates of Examples 1 and 2 were better than those of the control group, indicating that the compound ginseng flower preparation of the present invention was better than that of the control group, indicating that the Chinese medicine composition of the present invention has obvious therapeutic effect on psoriasis.

[0133] 5.2 Comparison of NHP scores after treatment:

[0134] The NHP scale is a comprehensive assessment of quality of life, consisting of a health questionnaire and personal life questions. Part 1 includes 38 items divided into six dimensions: physical activity, energy, pain, sleep, social connection, and emotional response. Part 2 covers seven dimensions: work, family care, social life, family life, sexual life, hobbies and interests, and vacations. The NHP scores, compiled from the questionnaire, are shown in Table 3.

[0135] Table 3 NHP scoring results

[0136]

[0137] As can be seen from Table 3, after treatment, the therapeutic effects of Example 1 and Example 2 groups were significantly better than those of the control group, and the self-limiting adverse reactions were effectively alleviated, with the differences being statistically significant (P < 0.05).

[0138] 5.3 Analysis of PASI and VAS scores in each group

[0139] PASI and VAS scores both adopted internationally accepted scoring indicators. The PASI and VAS score results of each group are shown in Table 4.

[0140] Table 4 PASI and VAS score results

[0141]

[0142] *Significantly different from the control group (P<0.05).

[0143] As can be seen from Table 4, the scores of Examples 1 and 2 are significantly lower than those of the control group, indicating that Examples 1 and 2 can improve skin erythema, infiltration, scaling, and thickening of lesions to varying degrees, and have a regulatory effect on immune function; the degree of itching is measured according to the internationally accepted visual analogue scale (VAS) for pain, and the VAS scores are all mild pain, which effectively relieves the patient's itching symptoms and does not affect the patient's normal life.

[0144] 5.4 Analysis of recurrence rate and adverse reaction incidence in each group

[0145] The patients were followed up for 4 months to observe the recurrence and adverse reactions in each group (see Table 5).

[0146] Table 5 Recurrence and adverse reactions

[0147]

[0148] *Significantly different from the control group (P<0.05).

[0149] As can be seen from Table 5, only one case of relapse occurred in Examples 1 and 2, and the eczema was self-improving, which was better than the control group. This shows that the Chinese medicine composition proposed by the present invention has almost no recurrence, and the Chinese medicine ingredients have no toxic side effects and no adverse symptoms.

[0150] 5.5 Analysis of recurrence rate and adverse reaction incidence in each group

[0151] The patients were followed up for 4 months to observe the recurrence and adverse reactions in each group (see Table 6).

[0152] Table 6 Recurrence and adverse reactions

[0153]

[0154] *Significantly different from the control group (P<0.05).

[0155] As can be seen from Table 6, only one case of relapse occurred in Examples 1 and 2, and the eczema was self-improving, which was better than the control group, indicating that the Chinese medicine composition proposed by the present invention had almost no recurrence.

[0156] The Chinese medicinal composition of the present invention has no toxic side effects. The patient's blood routine, urine routine, liver function, and kidney function were tested before and after treatment, and local skin and other adverse reactions were observed and recorded. After treatment with Example 1 and Example 2, the patient's blood routine, urine routine, liver function, and kidney function were all normal, with no adverse reactions.

[0157] In summary, the present invention is based on the principle that stimulating antioxidant defense enzymes through the Nrf2 / HO-1 pathway can alleviate the onset of psoriasis. The combination of monarch, minister, adjuvant, and guilder ingredients in the present invention's formula is scientifically and rationally formulated. The combination of anti-inflammatory, antioxidant, heat-clearing, blood-cooling, and antipruritic drugs effectively eliminates the cause of the disease and enhances its antipruritic effect, exerting anti-inflammatory, antiproliferative, and local vasoconstrictive effects. This combination has the advantages of increased efficacy and reduced toxicity, thereby promoting epithelial tissue repair, maintaining a dynamic balance of skin keratinization, and effectively preventing the recurrence of psoriasis, alleviating patient suffering. The present Chinese medicine composition is suitable for use in the preparation of psoriasis treatment drugs and is therefore widely marketed.

Claims

1. A Chinese medicine composition for external use for treating psoriasis, characterized in that: The invention is prepared from the following raw materials in parts by weight: 30-300 parts of purslane, 30-300 parts of sophora flavescens, 30-300 parts of white peony root bark, 30-200 parts of honeysuckle, 30-200 parts of kochia scoparia fruit, 30-200 parts of phellodendron amurense, 30-200 parts of orientalis leaves, 30-120 parts of red peony root and 30-120 parts of lithospermum officinale.

2. A pharmaceutical preparation for treating psoriasis, comprising an active ingredient and excipients, characterized in that: The active ingredient is the external-use Chinese medicine composition according to claim 1.

3. The pharmaceutical preparation according to claim 2, characterized in that The pharmaceutical preparation is any one of a cream, a liniment, a lotion, a paste and a medicated patch.

4. The pharmaceutical preparation according to claim 3, characterized in that The cream is prepared by the following process: 1) Weighing purslane, sophora flavescens, Dictamni bark, honeysuckle, Kochia scoparia, Phellodendron amurense, Platycladus orientalis leaves, Paeonia lactiflora, and Lithospermum officinale in proportion by weight, soaking the mixed herbs in cold water for at least 1 hour, then decocting them 2-3 times, adding 8-12 times the amount of water each time, and decocting them for 1-5 hours each time; collecting the filtrate after the decoction and concentrating it to 600-800 mL by heating and concentrating at normal pressure to obtain a Chinese herbal medicine extract, and mixing the Chinese herbal medicine extract with an aqueous phase additive to prepare an aqueous phase component; 2) Weigh the oil phase and heat in an 80°C water bath until melted. Weigh the water phase and heat to above 80°C. Once the oil phase is completely melted, pour the water phase into the oil phase and rapidly stir until uniformly mixed. Homogenize for 4-6 minutes, then continue stirring with a glass rod until the paste cools and solidifies to obtain a cream. The mass ratio of the oil phase to the water phase should be such that each gram of the resulting cream contains 0.7-0.9 g of the active ingredient.

5. The pharmaceutical preparation according to claim 4, characterized in that The oil phase includes one or more of an oil phase emulsifier, a penetration enhancer, a lubricant and a fatty alcohol.

6. The pharmaceutical preparation according to claim 5, characterized in that The oil phase emulsifier includes stearic acid, Span-60 and Tween-80, and the mass ratio of the three is 5-7:0.2-0.4:2.0-2.

3.

7. Use of the external Chinese medicine composition according to claim 1 or the pharmaceutical preparation according to any one of claims 2 to 6 in the preparation of a drug for treating psoriasis.

8. The use according to claim 7, wherein the external Chinese medicine composition or pharmaceutical preparation inhibits the onset of psoriasis via the JAK3 / STAT3 signaling pathway.

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