Medical application of helioscopinolide

Abstract

The invention relates to medical application of helioscopinolide. The invention relates to an application of helioscopinolide or a pharmaceutically acceptable salt thereof in preparation of a medicine for treating psoriasis. The compound can be used for preventing and treating psoriasis.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to an application of a diterpenoid compound. Background Art

[0002] Psoriasis has different types, including guttate psoriasis, erythrodermic psoriasis, pustular psoriasis and plaque psoriasis, and the common clinical features of most psoriasis types are erythema, skin thickening and scaling. Plaque psoriasis is the most common type of psoriasis, accounting for 80%-90% of psoriasis cases. It mainly manifests as erythema or scaly plaques with clear boundaries, affecting 2%-3% of the world's population. Psoriasis usually develops between the ages of 15 and 30, and its chronic and recurrent characteristics make it a clinically difficult disease to cure. Current research believes that the main pathogenesis of psoriasis is the overactivation of part of the adaptive immune system. Its inducing factors may involve genetics, immune system abnormalities and environmental stress. It has caused serious troubles to patients' lives and work. Summary of the invention

[0003] The purpose of the present invention is to provide a new use of lacquer lactone.

[0004] Specifically, the first aspect of the present invention provides the use of urushiolide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating psoriasis.

[0005] In a preferred embodiment, the above compound or a pharmaceutically acceptable salt thereof is used as the sole active ingredient in the preparation of a medicament for treating psoriasis.

[0006] The details of various aspects of the present invention will be described in detail in the following sections. The features, objectives and advantages of the present invention will become more apparent through the following description and the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0007] Figure 1 The effects of urushiol and urushiol on the skin lesions of psoriasis mice were shown.

[0008] Figure 2 The effects of zedoaria lactone and zedoaria on erythema and desquamation of the skin of psoriasis mice were reflected

[0009] Figure 3 The effects of zelactone and zelactone on the thickness and smoothness of the skin in psoriasis mice were shown

[0010] Figure 4 Effects of urushiolide and urushiolide on spleen weight in psoriasis mice DETAILED DESCRIPTION

[0011] The present invention provides the following formula (I) compound or its pharmaceutically acceptable salt in the preparation of medicine for preventing and treating acute pancreatitis:

[0012] The molecular formula of the lacquer lactone of the present invention is: 20 H 28 O 3， The molecular weight is: 316.4g / mol, and its structural formula is as follows:

[0013]

[0014] The zedoaryl lactone of the present invention can be purchased from Sikejie Biotechnology Co., Ltd. through commercial channels. Its purity meets the pharmaceutical standards.

[0015] The zelactone of the present invention can be used alone or in the form of a pharmaceutical composition. The pharmaceutical composition includes the zelactone of the present invention as an active ingredient and a pharmaceutically acceptable carrier. Preferably, the pharmaceutical composition of the present invention contains 0.1%-99.9% by weight of the zelactone of the present invention as an active ingredient. The "pharmaceutically acceptable carrier" will not destroy the pharmaceutical activity of the zelactone of the present invention, and its effective amount, that is, the amount that can play the role of a pharmaceutical carrier, is non-toxic to the human body.

[0016] The pharmaceutical carriers include, but are not limited to, lecithin, aluminum stearate, aluminum oxide, ion exchange materials, self-emulsifying drug delivery systems, Tween or other surfactants, serum proteins, buffer substances such as phosphates, aminoacetic acid, sorbic acid, water, salts, electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, magnesium silicate, partial glyceride mixtures of saturated fatty acids, and the like.

[0017] Other commonly used pharmaceutical excipients include binders (such as microcrystalline cellulose), fillers (such as starch, glucose, anhydrous lactose and lactose beads), disintegrants (such as cross-linked PVP, cross-linked sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose), lubricants (such as magnesium stearate), as well as absorption enhancers, adsorption carriers, flavoring agents, sweeteners, excipients, diluents, wetting agents, etc.

[0018] The galactone and its pharmaceutical composition of the present invention are prepared according to conventional methods in the art and can be administered through the gastrointestinal tract, parenteral tract or local skin route. Oral preparations include capsules, tablets, oral liquids, granules, pills, powders, pills, pastes, etc.; parenteral preparations include injections, etc.; local skin preparations include ointments, plasters, rubber plasters, pastes, liniments, lotions, film coatings, iontophoresis agents, etc. Preferably, the topical skin preparation is a topical skin preparation.

[0019] The administration routes of the urushiolide and the pharmaceutical composition thereof of the present invention can be oral, sublingual, transdermal, intramuscular or subcutaneous, skin mucosa, etc.

[0020] In addition to being made into medicines, various food additives such as antioxidants, pigments, enzyme preparations, etc. can also be added to the lacquer lactone of the present invention to prepare health food or health cosmetics according to conventional methods in the art.

[0021] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples without specifying specific conditions are usually performed under normal conditions or according to the conditions recommended by the manufacturer. Unless otherwise stated, all percentages, ratios, proportions, or parts are by weight.

[0022] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the methods of the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only.

[0023] The above features mentioned in the present invention or the features mentioned in the embodiments can be combined in any way. All the features disclosed in this patent specification can be used in combination with any combination form, and each feature disclosed in the specification can be replaced by any alternative feature that can provide the same, equal or similar purpose. Therefore, unless otherwise specified, the disclosed features are only general examples of equal or similar features.

[0024] Example 1 Study on the treatment of psoriasis with serpentine lactone

[0025] Experimental drugs: zedoaria lactone (CAS: 130466-20-5, molecular weight: 316.4 g / mol, HPLC purity ≥ 98%, Si Ke Jie Biotechnology Co., Ltd.); methotrexate (CAS: 59-05-2, molecular weight: 454.4 g / mol, HPLC purity ≥ 98%, MedChemexpress Biotechnology Co., Ltd., USA); imiquimod (CAS: 99011-02-6, molecular weight: 240.30 g / mol, HPLC purity ≥ 98%, Sichuan Mingxin Pharmaceutical Co., Ltd.)

[0026] Experimental animals: C57BL / 6 male mice weighing 20±2g, provided by the Experimental Animal Center of Shanghai University of Traditional Chinese Medicine, Animal Certificate No.: SYXK(Shanghai)2009-0069. They were placed in a conventional breeding environment and had free access to food and water.

[0027] Experimental methods: The imiquimod-induced psoriasis mouse model was established according to the literature (Hou Y, Zhang H, Zhu Y. Targeting upregulation of the immunosuppressive activity of MDSCs within dirubin as a novel strategy to alleviate psoriasis. Int Immunopharmacol.). C57BL / 6 male mice (20±2g) with uniform body weight were selected and adapted to feeding for 1 week. The hair on the back of the mice was first shaved with a shaver, and then a depilatory cream was applied to the back of the mice to completely remove the hair. On the second day, the test area on the back of each group of mice was smeared according to the following method. Smearing method:

[0028] Blank control group: no application;

[0029] Imiquimod group: apply imiquimod (62.5 mg / time, once a day, for 7 days);

[0030] Methotrexate group: methotrexate 1 mg / kg was administered by gavage after application of moquimod;

[0031] The zebu lactone group: 1 mg / kg zebu lactone was administered intragastrically after applying imiquimod;

[0032] Evaluation indicators: (1) Take photos 1-7 days after application to observe the skin color and skin lesions. (2) Score the skin erythema and scaling 1-7 days after application. (3) On the seventh day, the mice were killed, and the spleens of the mice in each group were removed, photographed and weighed.

[0033] Statistical analysis: All experimental data were repeated three times, and the results were expressed as mean ± standard deviation. GraphpadPrism 8 statistical software was used to analyze the experimental data using one-way ANOVA and LSD test. P < 0.05 was considered statistically significant.

[0034] Experimental results: Figure 1 The results showed that zebuli lactone had an effect on the back skin condition of mice. The back skin lesions of mice in the imiquimod group were significantly aggravated as the model was established; while the back skin lesions of mice in the zebuli lactone group were alleviated compared with the methotrexate group and the blank control group. Figure 2It reflects the effect of zedoaria lactone on skin erythema and desquamation. On days 1-7 of modeling, the erythema and skin lesions on the back of mice were scored daily. There were significant differences in erythema and skin lesions between the blank control group and the imiquimod group (P<0.001). This shows that imiquimod can promote the formation of psoriasis in mice, and the model was successfully established; methotrexate improved skin erythema and desquamation significantly compared with the imiquimod group (P<0.001). There were significant differences between the zedoaria lactone group and the imiquimod group (P<0.001). The above shows that zedoaria lactone can alleviate the symptoms of erythema and desquamation. Figure 3 HE staining was performed on the skin tissues of mice in each group. Compared with the blank control group, the skin structure of the model group was abnormal, the spinous layer was significantly thickened, the granular layer was thinned or disappeared, and the capillaries increased. Compared with the model group, the spinous layer thickening in the methotrexate group and the urushiolide group was restored, the capillaries decreased, and the inflammatory cell infiltration in the dermis decreased. Figure 4 The effect of zeolite on the spleen weight of mice was reflected. The mice were killed on the 7th day, and the spleens of mice were taken out. The spleen weight of mice in the blank control group was 71.5±6.6 mg, the spleen weight of mice in the imiquimod group was significantly enlarged, weighing 249.3±24.1 mg, the spleen weight of mice in the methotrexate group was 163.8±12.3 mg, and the spleen weight of mice in the zeolite group was 179.9±2.4 mg. Compared with the imiquimod group, there were significant differences in the methotrexate group and the zeolite group (methotrexate group P<0.001, zeolite group P<0.01), and both significantly reduced the spleen weight.

[0035] The above research results show that urushiolide can relieve psoriasis lesions, erythema and desquamation symptoms, and treat psoriasis caused by imiquimod.

[0036] Example 2 Comparative study of the treatment of psoriasis with zelactone and zelactone

[0037] Experimental drugs: Zeqi was purchased from Shanghai Kangqiao Chinese Medicine Pieces Co., Ltd. The Zeqi crude drug was boiled in water and filtered, and the filtrate was heated and concentrated. Finally, it was concentrated into a fluid extract, and an appropriate amount of Zeqi powder was added and heated and dried.

[0038] Experimental animals: C57BL / 6 male mice weighing 20±2g, provided by the Experimental Animal Center of Shanghai University of Traditional Chinese Medicine, Animal Certificate No.: SYXK(Shanghai)2009-0069. They were placed in a conventional breeding environment and had free access to food and water.

[0039] Experimental methods: The imiquimod-induced psoriasis mouse model was established according to the literature (Hou Y, Zhang H, Zhu Y. Targeting upregulation of the immunosuppressive activity of MDSCs within dirubin as a novel strategy to alleviate psoriasis. Int Immunopharmacol.). C57BL / 6 male mice (20±2g) with uniform weight were selected and adapted to feeding for 1 week. The hair on the back of the mice was first shaved with a shaver, and then a depilatory cream was applied to the back of the mice to completely remove the hair. On the second day, the test area on the back of each group of mice was smeared according to the following method. Smearing method:

[0040] The zebu lactone group: 1 mg / kg zebu lactone was administered intragastrically after applying imiquimod;

[0041] Zeqi group: Zeqi 1 mg / kg was administered by gavage after applying imiquimod;

[0042] Evaluation indicators: (1) Take photos 1-7 days after application to observe the skin color and skin lesions. (2) Score the skin erythema and scaling 1-7 days after application. (3) On the seventh day, the mice were killed, and the spleens of the mice in each group were removed, photographed and weighed.

[0043] Statistical analysis: All experimental data were repeated 5 times, and the results were expressed as mean ± standard deviation. GraphpadPrism 8 statistical software was used to analyze the experimental data using one-way ANOVA and LSD test. P < 0.05 was considered statistically significant.

[0044] Experimental results: Figure 1 The results showed that the lacquer had an effect on the back skin condition of mice. Compared with the lacquer lactone group, the lacquer group had ameliorated skin lesions on the back of mice, but the therapeutic effect was not as good as that of the lacquer lactone group (P<0.05). Figure 2 The results showed that zeqi had an effect on skin erythema and desquamation. During the 1st to 7th day of modeling, the erythema and skin lesions on the back of mice were scored daily. The erythema and skin lesions in the zeqi group were more serious than those in the zeqi lactone group (P<0.05). Figure 3 HE staining was performed on the skin tissues of mice in each group. Compared with the urushiol group, the spinous layer of the urushiol group was thickened, the granular layer was thinned or disappeared, and the number of capillaries increased. Figure 4 The effect of zelactone on the weight of mouse spleen was reflected. On the 7th day, the mice were killed and their spleens were taken out. The weight of the spleens of mice in the zelactone group was 175.68±22.75 mg, and the weight of the spleens of mice in the zelactone group was 179.9±2.4 mg, with no significant difference between the two groups.

[0045] The above research results show that both zelkova lactone and zelkova can relieve the symptoms of psoriasis, erythema and desquamation, and treat psoriasis caused by imiquimod. The effect of zelkova lactone in treating psoriasis is better than that of zelkova.

[0046] The various aspects of the present invention have been described above. However, it should be understood that, without departing from the spirit of the present invention, equivalent changes and modifications may be made by those skilled in the art, and the changes and modifications also fall within the scope of the claims of the present application.

Claims

1. Use of urushiolide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating psoriasis.

2. The use of urushiolide or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that: The urushiolide or its pharmaceutically acceptable salt is used as the sole active ingredient for preparing a medicine for treating psoriasis.

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