Traditional Chinese medicine composition for treating psoriasis as well as preparation method and application thereof

Abstract

The invention relates to a traditional Chinese medicine composition for treating psoriasis as well as a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following raw materials: herba portulacae, radix sophorae flavescentis, cortex dictamni, honeysuckle flower, fructus kochiae, cortex phellodendri, cacumen biotae, radix paeoniae rubra and radix arnebiae seu lithospermi. The traditional Chinese medicine composition has the advantages of scientific and reasonable formula, synergistic interaction, few components and controllable quality. In the formula, the compatibility of monarch, minister, assistant and guide is scientific and reasonable, anti-inflammatory and immunoregulation compatibility of heat-clearing, blood-cooling and itching-relieving medicines can effectively remove pathogenesis and enhance the itching-relieving effect, the effects of anti-inflammatory, anti-proliferation and local vasoconstriction are achieved, the advantages of effect enhancement and toxicity reduction are achieved, and the risk of relapse can be reduced. Therefore, epithelial tissue repair is promoted, skin keratinization dynamic balance is maintained, relapse of psoriasis is effectively prevented, and pain of patients is reduced.

Description

Technical Field

[0001] The present invention belongs to the field of Chinese medicine compositions, and specifically relates to a Chinese medicine composition for treating psoriasis and a pharmaceutical preparation thereof, a preparation method of the pharmaceutical preparation, and application of the 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. Typical skin lesions are localized or widespread scaly erythema or plaques. In addition to skin lesions and nail involvement, psoriasis patients often experience joint symptoms and even irreversible joint deformities. Moderate to severe psoriasis patients often have obesity, hypertension, Crohn's disease, metabolic syndrome, depression and other diseases, which seriously affect the quality of life of patients. In recent years, the incidence and prevalence of psoriasis have increased year by year. At present, the treatment options of Western medicine mainly include topical drugs, phototherapy, systemic drugs and biological agents. Standardized treatment can effectively relieve symptoms. However, psoriasis cannot be completely cured at present and is prone to relapse. Patients need long-term systemic treatment. Due to the various adverse reactions of long-term systemic treatment, high treatment costs and repeated symptoms, patients often have poor satisfaction with treatment and low compliance. Therefore, more and more psoriasis patients are receiving complementary and alternative medicine treatment.

[0003] Chinese medicine treatment is an indispensable part of complementary and alternative medicine, and has a long history in the treatment of psoriasis. Based on the principles of combining disease and syndrome, syndrome differentiation and treatment, holistic treatment, and staged treatment, Chinese medicine can provide individualized treatment plans for psoriasis patients, and has advantages that cannot be replaced by other therapies. In addition, more and more evidence shows that Chinese medicine can improve patients' clinical symptoms, reduce the psoriasis area and severity index scores, reduce the side effects of Western medicine, delay the recurrence of psoriasis, and improve the quality of life.

[0004] Chinese patent CN114272339 discloses a Chinese medicine composition for treating eczema, skin allergies or psoriasis and its preparation method. The Chinese medicine composition contains 20 components, which are numerous and complex, difficult to control quality, 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 there will be recurrence.

[0005] Chinese patent CN116850236 discloses a Chinese medicine composition for external use for treating psoriasis, its preparation and application. From the perspective of drug action mechanism, it analyzes that its drug composition inhibits the expression of related inflammatory factors such as IL-1β, IL-6, IL-8, IL-17A, IL-22, IL-23, etc., alleviates the symptoms of psoriasis-like skin lesions in mice, and improves inflammation and autoimmune reactions. However, its components contain the root of Torch Flower, which has obvious side effects and has an inhibitory effect on gonads and bone marrow, and is not suitable for long-term use.

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

[0007] The present invention provides a Chinese medicine composition for treating psoriasis, a preparation method and application thereof, and aims to provide a Chinese medicine composition and preparation thereof which are still lacking in the field of treating psoriasis and have good efficacy, avoid recurrence, have controllable quality and are free of toxic side effects.

[0008] Technical solution:

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

[0010] Furthermore, the Chinese medicine composition is made of the following raw materials in parts by weight: 1-300 parts of Portulaca oleracea, 1-300 parts of Sophora flavescens, 1-300 parts of Dictamni cortex, 1-300 parts of Honeysuckle, 1-300 parts of Kochia scoparia, 1-300 parts of Phellodendron amurense, 1-300 parts of Platycladus orientalis leaves, 1-200 parts of Red Peony Root, and 1-200 parts of Lithospermum officinale.

[0011] Preferably, the Chinese medicine composition is made of 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, wherein the pharmaceutical preparation 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 preparation, 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) Weigh purslane, sophora flavescens, Dictamni cortex, honeysuckle, Kochia scoparia, Phellodendron amurense, Platycladus orientalis leaves, red peony root and lithospermum officinale according to the weight ratio, soak the mixed drugs in cold water for 1 hour and then decoct them 2-3 times, adding 8-12 times of water (mass volume ratio g / mL) each time, and decocting for 1-5 hours each time; collect the filtrate after decoction and concentrate the filtrate to 600-800mL by normal pressure heating and concentration method to obtain a traditional Chinese medicine extract, and mix the traditional Chinese medicine extract with an aqueous phase additive as 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, a preservative, etc., which can be obtained through a limited number of experiments according to actual needs.

[0016] 2) Weigh the oil phase component, place it in a 80°C water bath and heat it until it melts; 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 quickly stir it evenly, homogenize for 5 minutes, and continue stirring with a glass rod until the paste cools and solidifies to obtain an emulsion; the mass ratio of the oil phase to the water phase must satisfy the requirement that each 1g of the final emulsion contains 0.7 to 0.9g of 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. The specific amount 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 the preparation of a drug for treating psoriasis.

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

[0021] (III) Beneficial effects

[0022] The present invention proposes a Chinese medicine composition for treating psoriasis, a pharmaceutical preparation of the Chinese medicine composition, a preparation method of the pharmaceutical preparation, and the use of the Chinese medicine composition or the pharmaceutical preparation in preparing a medicine for treating autoimmune skin diseases. The Chinese medicine composition of the present invention has a scientific and reasonable prescription, synergistic synergy, and few ingredients with controllable quality. It is composed of only 9 Chinese medicines, and the prescription is simple, which overcomes the shortcomings of the current Chinese patent medicine prescription for treating psoriasis, which is complex in composition and difficult in quality control. The present invention proposes to use Sophora flavescens, Dictamni cortex, and Portulaca oleracea as monarch medicines, and to supplement with anti-inflammatory, blood-cooling, blood-activating, and antipruritic Chinese medicines, honeysuckle, Kochia scoparia, and Phellodendron as ministers, Platycladus orientalis leaves as adjuvants, and red peony root and lithospermum officinale as messengers. The monarch, minister, assistant, and messenger compatibility in the prescription is scientific and reasonable, and the anti-inflammatory, immunomodulatory, heat-clearing, blood-cooling, and antipruritic drugs can effectively eliminate the cause of disease and enhance the antipruritic effect, exert anti-inflammatory, anti-proliferative and local vasoconstriction effects, have the advantages of synergistic and toxicity reduction, and can reduce the risk of recurrence. Thereby promoting epithelial tissue repair, maintaining the dynamic balance of skin keratinization, and effectively preventing the recurrence of psoriasis, reducing the patient's pain, and overcoming the shortcomings of Western medicine such as single target, many restrictions on combined medication, and large toxic and side effects of some drugs.

[0023] Mouse tests and clinical trials have proved that the Chinese medicine composition and drug preparation proposed in the present invention have good efficacy in the treatment of psoriasis, almost no recurrence, no toxic side effects, and are suitable for promotion. In particular, the compound ginseng flower cream has good efficacy, controllable quality, convenient carrying, easy storage, few side effects, abundant resources, and low price, which is conducive to solving the current problem of expensive medical treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The skin lesions on the back of mice;

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

[0026] Figure 3 The epidermal thickness 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 skin 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 skin 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 skin 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 each group of mice (compared with the blank group, ### P < 0.001, ## P<0.01; compared with the model group, **P<0.01, *P<0.05);

[0032] Fig. 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 in conjunction with the embodiments and drawings. It should be understood that the specific implementation methods described herein are only used to explain the present invention, rather than to limit the present invention.

[0034] Psoriasis is an immune-mediated chronic, recurrent, inflammatory, systemic disease induced by the interaction between individuals and the environment. The core mechanism of psoriasis is the excessive proliferation and abnormal differentiation of epidermal keratinocytes (KC) caused by immune pathways related to interleukin 23 (IL-23) and helper T cell 17 (Th17) cells. Various cells such as T cells, dendritic cells, neutrophils and keratinocytes cause characteristic changes in psoriasis, including neutrophil infiltration and angiogenesis, through cytokines such as tumor necrosis factor α (TNF-α), gamma interferon (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 links of psoriasis by transmitting signals of multiple cytokines such as 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 which the partial overactivation of the adaptive immune system is considered to be the central link in the pathogenesis of psoriasis.

[0035] The present invention provides a Chinese medicine composition (compound ginseng flower preparation) for treating psoriasis, which plays anti-inflammatory, immunosuppressive, anti-proliferative and local vasoconstrictive effects by down-regulating genes encoding pro-inflammatory cytokines, and can reduce the risk of recurrence. It is made from the following raw materials: purslane, sophora flavescens, Dictamni, honeysuckle, Kochia scoparia, Phellodendron amurense, Platycladus orientalis leaves, red peony root and lithospermum officinale.

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

[0037] Purslane - belongs to the heart meridian, liver meridian, spleen meridian, and large intestine meridian; Efficacy: clearing away heat and detoxifying, cooling blood and stopping bleeding, anti-inflammatory, immune regulation, anti-oxidation, can relieve itching and improve symptoms such as erythema and scaling on the skin;

[0038] Sophora flavescens - belongs to the liver meridian, kidney meridian, large intestine meridian, small intestine meridian, bladder meridian, heart meridian; Efficacy: clearing away heat and dampness, dispelling wind and killing insects, immune regulation, detoxification and anti-inflammatory;

[0039] Dictamni peel - belongs to the spleen meridian, stomach meridian, and bladder meridian; Efficacy: clearing away heat and dampness, dispelling wind and detoxifying, immune regulation, and can inhibit cell senescence induced by oxidative stress. Dictamni peel contains rich flavonoids and has anti-inflammatory effects;

[0040] Honeysuckle - belongs to the lung meridian, heart meridian, stomach meridian; Effects: clearing away heat and detoxifying, anti-inflammatory, tonifying deficiency and curing wind;

[0041] Kochia seeds - enter the kidney meridian and bladder meridian; Efficacy: clearing away heat and dampness, dispelling wind and relieving itching. Kochia seeds and its main saponin momordica charantia can prevent inflammation;

[0042] Huangbai——Enters the kidney meridian and bladder meridian; Effects: clearing away heat and dampness, purging fire and detoxifying, anti-inflammatory, immune regulation;

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

[0044] Red Peony Root——Enters the Liver Channel; Effects: Clearing away heat and cooling blood, promoting blood circulation and removing blood stasis, anti-inflammatory, anti-oxidation, immune regulation;

[0045] Lithospermum officinale - enters the heart, pericardium and liver meridians; Efficacy: cooling blood, activating 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 to use Sophora flavescens, Dictamni cortex, and Portulaca oleracea, which have the effects of clearing away heat and detoxifying, anti-inflammatory, and immunomodulating, as the main medicine, and to supplement with anti-inflammatory, blood cooling, blood circulation, and antipruritic Chinese medicines, with honeysuckle, Kochia scoparia and Phellodendron chinense as ministerial medicines, with Platycladus orientalis leaves as adjuvants, and red peony root and Lithospermum officinale as messenger medicines. Among them, the main medicines Sophora flavescens, Dictamni cortex, and Portulaca oleracea have anti-inflammatory and immunomodulating effects; they can inhibit the expression of JAK and STAT3 by reducing the levels of inflammatory factors such as TNF-α, IFN-γ, IL-6, and IL-8, and increasing the expression of SOCS1, hindering the activation of the JAK / STAT3 signaling pathway, thereby inhibiting KC proliferation, and regulating T lymphocyte activation and balance. The ministerial medicines Honeysuckle, Kochia scoparia and Phellodendron chinense are all Chinese medicines with the effects of clearing away heat and detoxifying, anti-inflammatory, and antipruritic, which can assist the main medicine in playing the role of anti-inflammatory and immunomodulating, and play the role of antipruritic. 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 is scientific and reasonable. The combination of anti-inflammatory and immunomodulatory drugs with heat-clearing, cooling blood and antipruritic drugs can effectively eliminate the cause of the disease and enhance the antipruritic effect, exert anti-inflammatory, anti-proliferative and local vasoconstriction effects, have the advantages of increasing efficacy and reducing toxicity, and can reduce the risk of recurrence. It can promote epithelial tissue repair, maintain the dynamic balance of skin keratinization, and effectively prevent the recurrence of psoriasis and reduce the pain of patients.

[0049] Example 1

[0050] Chinese medicine bath is guided by TCM syndrome differentiation and treatment. It uses Chinese medicine decoction to bathe the whole body and parts of the patient, so that the medicine can be directly absorbed through the skin to exert its effect. The compound ginseng flower preparation composed of purslane, sophora flavescens, Dictamni cortex, honeysuckle, Kochia scoparia, Phellodendron chinense, Platycladus orientalis, red peony root, and lithospermum officinale is preferably diluted with warm water with 30g of each medicine in a ratio of 1:1 (mass volume ratio g / L) according to the dosage specified in the Pharmacopoeia of the People's Republic of China (2010 Edition) and then bathed for 20 minutes. When the skin is heated during the medicinal bath, the blood vessels expand, and the Chinese medicine is directly absorbed through the skin and other parts, acting on the skin lesions and exerting its function. It can soften and remove psoriasis lesions, shorten the course of treatment, reduce the incidence of adverse reactions, and significantly improve the quality of life of patients with psoriasis.

[0051] Example 2

[0052] The dosage forms applied topically to the skin can be divided into different dosage forms such as bath preparations, creams, liniments, lotions, sprays, gels, pastes, patches, skin patches, ointments and oils. This embodiment uses creams as an example for illustration. Cream preparations are promising drug carriers for skin drug delivery. Creams are semisolid emulsions containing one or more dissolved or dispersed active substances, which can be defined as a two-phase system in which the dispersed phase or internal phase is finely and evenly dispersed in the continuous phase or external phase. Depending on the nature of the dispersed phase, oil-in-water creams (o / w) or water-in-oil creams (w / o) can be obtained. After optimization and screening experiments, the aqueous phase components of this embodiment include Chinese medicine extract and glycerol, and the mass ratio of the two is 250-280:48-55. In this embodiment, the aqueous phase is 250-280g of Chinese medicine extract and 48-55g of glycerol; the oil phase includes stearic acid, glyceryl monostearate, white vaseline, liquid paraffin, Span-60, Tween-80 and ethyl hydroxybenzoate, 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 56-65g of stearic acid, 20-25g of glyceryl monostearate, 35-45g of white vaseline, 35-45g of liquid paraffin, 3-4g of Span-60, 15-20g of Tween-80, and 0.1-1.2g of ethyl hydroxybenzoate. Each gram of cream contains 0.7 to 0.9 grams of active ingredients. Under these conditions, the compound ginseng flower cream obtained has a fine texture, is refreshing and easy to spread, has a good smell, and is brown in color. It meets the appearance and sensory evaluation of the product, 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 according to actual needs, and can satisfy the appearance and sensory evaluation of the product.

[0054] Preparation method:

[0055] 1) Preparation of Chinese medicine extract:

[0056] Weigh 200g each of purslane, sophora flavescens, white mulberry bark, honeysuckle, kochia scoparia, phellodendron, and arborvitae leaves, 70g each of red peony root and lithospermum officinale, put the medicine (a total of 1540g) into a decoction bag, soak in cold water for 1 hour and decoct twice, add 10 times (15.4L) of water each time, and decoct for 2 hours each time. Collect the filtrate after two decoctions and place it in a container, and concentrate the filtrate to 800ml of Chinese medicine extract by heating and concentrating at normal pressure. Take 280g of Chinese medicine extract and 55g of glycerin as the aqueous phase. 2) Preparation of compound ginseng flower cream:

[0057] Select O / W dosage form, weigh the oil phase components, stearic acid 56g, monostearate glyceryl 20g, white vaseline 35g, liquid paraffin 35g, Span-60 3g, Tween-80 15g, ethyl hydroxybenzoate 0.1g, place in 80℃ water bath and heat until melted; heat the water phase to above 80℃; after the oil phase is completely melted, pour the water phase into the oil phase and stir quickly and evenly, use a high-speed dispersing homogenizer for 5min, and continue to stir with a glass rod until the paste cools and solidifies. Get the compound ginseng flower cream; each 1g of the cream finally contains 0.78g of active ingredient.

[0058] Example 3

[0059] 1) Preparation of Chinese medicine extract:

[0060] Weigh 100g each of Portulaca Oleracea, Sophora flavescens, Dictamni Cortex, Honeysuckle, Kochia scoparia, Phellodendron chinense, and Platycladus orientalis leaves, 50g each of Paeonia lactiflora and Lithospermum officinale, put the medicine (800g in total) into a decoction bag, soak in cold water for 1 hour and decoct twice, add 10 times (8L) of water each time, and decoct for 2 hours each time. Collect the filtrate after decoction twice and place it in a container, and the filtrate is concentrated to 600ml of Chinese medicine extract by heating and concentrating at normal pressure. Take 250g of Chinese medicine extract and 48g of glycerol as the aqueous phase.

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

[0062] Select O / W dosage form, weigh the oil phase components, stearic acid 60g, monostearate glyceryl 22g, white vaseline 40g, liquid paraffin 40g, Span-60 3g, Tween-80 17g, ethyl hydroxybenzoate 0.3g, place in 80℃ water bath and heat until melted; heat the water phase to above 80℃; after the oil phase is completely melted, pour the water phase into the oil phase and stir quickly and evenly, use a high-speed dispersing homogenizer for 5min, and continue to stir with a glass rod until the paste cools and solidifies. Get the compound ginseng flower cream; each 1g of the cream finally obtained contains 0.75g of active ingredient.

[0063] Example 4

[0064] 1) Preparation of Chinese medicine extract:

[0065] Weigh 300g each of purslane, sophora flavescens, Dictamni root, honeysuckle, Kochia scoparia, Phellodendron chinense, Platycladus orientalis leaves, 120g each of red peony root and lithospermum officinale, put the medicine (a total of 2340g) into a decoction bag, soak in cold water for 1 hour and decoct twice, add 10 times (23.4L) of water each time, and decoct for 2 hours each time. Collect the filtrate after two decoctions and place it in a container, and concentrate the filtrate to 800ml of Chinese medicine extract by heating and concentrating at normal pressure. Take 260g of Chinese medicine extract and 50g of glycerin as the aqueous phase. 2) Preparation of compound ginseng flower cream:

[0066] Select O / W dosage form, weigh the oil phase components, stearic acid 65g, monostearate glyceryl 25g, white vaseline 45g, liquid paraffin 45g, Span-60 4g, Tween-80 18g, ethyl hydroxybenzoate 1.0g, place in 80℃ water bath and heat until melted; heat the water phase to above 80℃; after the oil phase is completely melted, pour the water phase into the oil phase and stir quickly and evenly, use a high-speed dispersing homogenizer for 5min, and continue to stir with a glass rod until the paste cools and solidifies. Get the compound ginseng flower cream; each 1g of the cream finally obtained contains 0.88g of active ingredient.

[0067] Comparative Example 1

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

[0069] Comparative Example 2

[0070] The difference from Example 2 is that the main drug does not contain Purslane, 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 drug 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%) of compound ginseng flower cream group (IMQ+SH+L), a medium dose (68%) of compound ginseng flower cream group (IMQ+SH+M), a high dose (76%) of 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 at 8 am every day, once a day, for 7 consecutive days to establish the model. At the same time as the modeling, at 14:00 every day, the mice in the low, medium and high doses of compound ginseng flower cream group, comparative examples 1-3, and calcipotriol cream in the calcipotriol group were given once a day. 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) score in mice

[0084] The psoriasis skin area and severity of illness (PASI) score was used to score the skin lesions of mice 24 hours after the last administration, including erythema, scaling, and thickening, each with a score of 0-4: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = extremely 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 solution for 24 hours, then dehydrated, waxed, embedded, cooled, sliced ​​to make pathological white slides, and then stained with hematoxylin-eosin. Finally, the pictures were collected and observed, and the epidermal thickness was measured.

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

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

[0089] Observation under a microscope showed that the positive staining part was brown-yellow. The images were collected and analyzed, and three fields of view were randomly selected. The photos were analyzed for optical density quantification 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 eyeballs of the mice 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] The total RNA in the mouse skin lesion tissue was extracted by Trizol method, and the total RNA concentration was determined. The reagents were prepared according to the instructions of the reverse transcription kit, and the RNA was reverse transcribed into cDNA, and then real-time fluorescence quantitative polymerase chain reaction was performed. 18s was used as the internal reference gene, and the relative expression of JAK3, STAT3, and IL-17A mRNA was calculated by 2-ΔΔCt method.

[0095] 2.7 Statistical methods

[0096] The collected data were summarized using EXCEL, and the quantitative data were expressed as mean ± standard deviation (x ± s). GraphPad Prism10 software was used for drawing and statistical analysis. The t test was used for pairwise comparison of data, and one-way analysis of variance was used for inter-group comparison of data. 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 there was no erythema, scaling and thickening of the skin of the mice in the blank group, so the PASI score was 0. Compared with the blank group, the PASI score of the mice in the model group was significantly increased, and the difference was statistically significant; compared with the model group, the PASI scores of the mice in the compound ginseng flower cream group and the calcipotriol group were significantly reduced, and the difference was statistically significant. Compared with comparative 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 in comparative examples 1 to 3. It shows that the formulation of the Chinese medicine composition of the present invention is scientific and reasonable, synergistic, and cannot be obtained by simple replacement. It can exert anti-inflammatory, anti-proliferative and local vasoconstriction effects, has good efficacy in the treatment of psoriasis, and has no toxic side effects.

[0103] from Figure 1 It can be seen that on the 8th day, the skin of the mice in the blank group was smooth and delicate, without erythema, scaling, or thickening; compared with the blank group, erythema and flaky scaling were visible on the skin of the mice in the model group, accompanied by skin thickening; compared with the model group, the erythema and scaling of the skin of the mice in the high-dose compound ginseng flower cream group and the calcipotriol group 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 group 1 to 3 were slightly reduced, and the skin thickening was slightly improved, and the improvement effect was significantly lower than that of the high-dose compound ginseng flower cream group.

[0104] 3.3 Epidermal thickness

[0105] The epidermal thickness of each group of mice was measured. Figure 3 As shown, compared with the blank group, the epidermal thickness of the mice in the model group was significantly thickened, and the difference was statistically significant; 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 thinned, and the difference was statistically significant. The high-dose compound ginseng flower cream group was better than the low- and medium-dose compound ginseng flower creams, and the epidermal thickness of the mice in the comparative examples 1 to 3 with the same high dose was thinner, which shows that the Chinese medicine composition of the present invention is scientific and reasonable, and synergistic.

[0106] 3.4 Histological morphology of mice in each group

[0107] HE staining results showed that Figure 4 As shown (Comparative Examples 1 to 3 with higher PASI scores are not considered), no hyperkeratosis and parakeratosis were observed in the skin of mice in the blank group, the thickness of the epidermis was normal, and no inflammatory cell infiltration was observed in the superficial dermis. Compared with the blank group, hyperkeratosis with parakeratosis, decreased granular layer cells, thickened stratum spinosum, epidermal protrusions extending downward in a "clamp-shaped" manner, thickened epidermis, and infiltration of lymphocytes and neutrophils in the superficial dermis were observed in the skin of mice in the model group, which was 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 was improved, and the infiltration of inflammatory cells in the superficial dermis was reduced.

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

[0109] like Figure 5-7 As shown in the figure, 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 difference was 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 reduced, among which the high-dose compound ginseng flower cream group and calcipotriol group had the most obvious decrease.

[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 serum of the model group were significantly increased; compared with the model group, the levels of IL-6, IL-1β and TNF-α in 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 the expression of IL-17A, JAK3 and STAT3 mRNA in mouse skin tissue:

[0113] like Fig. 9 As shown in the results, compared with the blank group, the mRNA expression levels of IL-17A, JAK3, and STAT3 in the skin lesions of mice in the model group were significantly increased; compared with the model group, the mRNA expression levels of IL-17A, JAK3, and STAT3 in the skin lesions of 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 the present invention can reduce the inflammatory response of the skin lesions of psoriasis model mice induced by IMQ, improve the psoriasis skin lesions of mice, and the high-dose group has the best effect. High-dose compound ginseng flower cream can effectively relieve the psoriasis skin lesions of mice induced by imiquimod, reduce the epidermal thickness of mice, inhibit the proliferation of keratinocytes, and reduce lymphocyte infiltration. The compound ginseng flower cream may play a role in treating psoriasis by inhibiting the JAK3 / STAT3 signaling pathway and reducing the secretion of proinflammatory cytokines.

[0115] (II) 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 Affiliated to China Medical University.

[0120] 3. Inclusion criteria

[0121] Volunteer to participate in the study and sign the informed consent. Male or female aged 18-65 years. Refer to the diagnostic criteria for psoriasis vulgaris established by "Clinical Dermatology" and clinically diagnosed with psoriasis vulgaris. The condition meets the requirements of moderate to severe psoriasis vulgaris, that is, the psoriasis body surface area (BSA) is ≥10%, and the Psoriasis Area and Severity Index (PASI) score is >10 points and ≤20 points. No systemic or local use of glucocorticoids, immunosuppressants, biological agents, retinoic acid, phototherapy, etc. within one month before enrollment.

[0122] 4. Research treatment options

[0123] The control group was given the medicinal bath treatment of Example 1, 30 g of each of 8 Chinese medicines including Sophora flavescens, Dictamni cortex, and Portulaca oleracea were decocted and diluted with warm water in a ratio of 1:1, and then bathed for 20 minutes, once a day;

[0124] The cream of Example 2 was applied externally, only to the affected area, and the drug dosage was 1 fingertip unit of the subject, evenly applied to 2% of the body surface area, once a day;

[0125] The positive control group was given fluticasone propionate cream for external application, which was applied only to the affected area. The drug dosage was 1 fingertip unit of cream evenly applied to 2% of the body surface area, once a day. Each group was treated for 4 weeks and followed up for 4 weeks. During the treatment, the subjects were not allowed to use any other local treatments, phototherapy or systemic treatments that might affect the evaluation of psoriasis.

[0126] 5. Analysis of test results

[0127] 5.1 Clinical efficacy analysis:

[0128] Six groups of clinical efficacy observation, judgment criteria: (1) efficacy index (skin lesion improvement rate) = (PASI score before treatment - PASI score after treatment) / PASI score before treatment * 100%; (2) cured: efficacy index ≥ 95%; skin lesions completely disappeared, leaving only a few inactive lesions or pigment changes; (3) markedly effective: 95% > efficacy index ≥ 60%; skin lesions disappeared in detail, and symptoms improved significantly; (4) effective: 60% > efficacy index ≥ 30%; symptoms improved; (5) ineffective: 30% > efficacy index, 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, the total effective rate of Examples 1 and 2 was better than that of the control group, which shows that the compound ginseng flower preparation of the present invention is 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 scale for comprehensively evaluating the quality of life. It consists of two parts: a health questionnaire and personal life questions. Part 1 includes 38 items, divided into 6 dimensions, namely physical activity, energy, pain, sleep, social connection and emotional response. Part 2 includes 7 aspects, including work, caring for the family, social life, family life, sex life, hobbies and interests, and vacation. The NHP score results are summarized 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, and the difference was 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 skin lesions to varying degrees, and have a regulatory effect on immune function; the degree of itching is based on the internationally accepted visual analogue scale (VAS) for pain, and the VAS scores are all mild pain, which effectively relieves the itching symptoms of patients and does not affect the normal life of patients.

[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 Relapse 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, indicating that the Chinese medicine composition proposed in 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 Relapse 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 has almost no relapse.

[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 are tested before and after treatment, and the skin local and any other adverse reactions are observed and recorded. After treatment with Example 1 and Example 2, the patient's blood routine, urine routine, liver function, and kidney function are all normal, without adverse reactions.

[0157] In summary, the present invention is based on the fact that stimulating antioxidant defense enzymes through the Nrf2 / HO-1 pathway can alleviate the onset of psoriasis. The combination of monarch, minister, assistant and envoy in the present invention is scientific and reasonable. The combination of anti-inflammatory, antioxidant, heat-clearing, blood-cooling and antipruritic drugs can effectively eliminate the cause of the disease and enhance the antipruritic effect, exert anti-inflammatory, anti-proliferative and local vasoconstriction effects, and have the advantages of increasing efficacy and reducing toxicity, thereby promoting epithelial tissue repair, maintaining the dynamic balance of skin keratinization, and effectively preventing the recurrence of psoriasis and reducing the pain of patients. The Chinese medicine composition of the present invention is suitable for application and promotion in the preparation of drugs for treating psoriasis.

Claims

1. A Chinese medicine composition for treating psoriasis, characterized in that: It is made from the following raw materials: purslane, sophora flavescens, Dictamni cortex, honeysuckle, Kochia scoparia, Phellodendron amurense, Platycladus orientalis leaves, red peony root, and Lithospermum officinale.

2. A Chinese medicine composition for treating psoriasis according to claim 1, characterized in that: The invention is prepared 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, 1-300 parts of oriental arborvitae leaves, 1-200 parts of red peony root and 1-200 parts of lithospermum officinale.

3. A Chinese medicine composition for treating psoriasis according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 20-200 parts of purslane, 20-200 parts of sophora flavescens, 20-200 parts of dittany bark, 20-200 parts of honeysuckle, 20-200 parts of kochia scoparia, 20-200 parts of phellodendron, 20-200 parts of orientalis leaves, 20-100 parts of red peony root and 20-100 parts of lithospermum officinale.

4. A pharmaceutical preparation for treating psoriasis, the pharmaceutical preparation comprising an active ingredient and excipients, characterized in that: The active ingredient is the Chinese medicine composition according to any one of claims 1 to 3.

5. The pharmaceutical preparation according to claim 4, characterized in that The pharmaceutical preparation is any one of a bath preparation, a cream, a liniment, a lotion, a spray, a gel, a paste, a medicated patch, a skin patch, an ointment and an oil.

6. The pharmaceutical preparation according to claim 5, characterized in that The cream is prepared by the following process: 1) Weighing purslane, sophora flavescens, Dictamni cortex, honeysuckle, Kochia scoparia, Phellodendron amurense, Platycladus orientalis, red peony root and lithospermum officinale according to the weight ratio, soaking the mixed drugs in cold water for at least 1 hour and then decocting 2-3 times, adding 8-12 times of water each time, and decocting for 1-5 hours each time; collecting the filtrate after decoction and concentrating the filtrate to 600-800 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 as an aqueous phase component; 2) Weigh the oil phase component, place it in a 80°C water bath and heat it until it melts; 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 quickly stir it evenly, homogenize for 4 to 6 minutes, and continue stirring with a glass rod until the paste cools and solidifies to obtain an emulsion; the mass ratio of the oil phase to the water phase must satisfy the requirement that each 1g of the final emulsion contains 0.7 to 0.9g of active ingredient.

7. The pharmaceutical preparation according to claim 6, characterized in that The oil phase includes one or more of an oil phase emulsifier, a penetration enhancer, a lubricant and a fatty alcohol.

8. The pharmaceutical preparation according to claim 7, 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.

9. Use of the traditional Chinese medicine composition according to any one of claims 1 to 3 or the pharmaceutical preparation according to any one of claims 4 to 8 in the preparation of a drug for treating psoriasis.

10. The use according to claim 9, wherein the Chinese medicine composition or pharmaceutical preparation inhibits the onset of psoriasis via the JAK3 / STAT3 signaling pathway.

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