Application of obakunone in preparation of medicine for preventing and treating psoriasis

Abstract

The invention relates to application of obakunone in preparation of a medicine for preventing and treating psoriasis. According to the application, the medicine is composed of obakunone and medically acceptable auxiliary materials, wherein the mass percentage content of obakunone in the medicine is 0.3%-15%. The medicine in the application has a remarkable effect of preventing and treating psoriasis.

Description

Technical Field

[0001] The invention relates to a pharmaceutical product containing organic active ingredients, in particular to a medicine containing sesquiterpenoid compounds. The medicine is suitable for preventing and treating psoriasis. Background Art

[0002] Psoriasis is a common and complex chronic skin disease characterized by excessive proliferation of keratinocytes, infiltration of inflammatory cells and hypervascularization of dermal tissue. It accounts for about 2%-3% of the global population, especially in European and American countries where the incidence is high and increasing year by year. The disease is not only difficult to treat and prone to relapse, but also requires long-term treatment, occupies a large amount of medical resources and is very expensive. It is also prone to cause complications such as psoriatic arthritis, metabolic syndrome and malignant tumors. Treatments for psoriasis include topical treatment, systemic treatment and phototherapy. Although topical medications such as vitamin D derivatives and glucocorticoids are effective, there is a risk of metabolic disorders and "rebound" phenomena; systemic treatment drugs such as acitretin, methotrexate and cyclosporine are also limited by their side effects such as dry skin and mucous membranes, hepatotoxicity and liver and kidney damage. At present, there is no particularly ideal treatment for psoriasis, and patients need to choose a suitable treatment plan for long-term management under the guidance of a doctor.

[0003] Obacunone is a compound extracted from Phellodendron amurense, which has multiple pharmacological effects such as anti-inflammatory, antibacterial, antiviral and anti-tumor. However, there is still no report in the literature on the use of obacunone in the treatment of psoriasis. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a new use of chloroquine, that is, a new application in pharmaceutical manufacturing.

[0005] The above-mentioned new application in pharmaceutical manufacturing is the application of pyruvate in the preparation of drugs for preventing and treating psoriasis, wherein the chemical structure of pyruvate is shown in the following formula (I):

[0006]

[0007] In the above application, the said cork ketone can be extracted from natural plants such as cork ketone by conventional methods, or can be prepared by synthesis or other methods.

[0008] In the above application, the drug is composed of flavonoids and medically acceptable excipients, wherein the mass percentage of flavonoids in the drug is 0.3% to 15%.

[0009] In the above application, the drug can be a clinically acceptable gel, ointment, capsule or tablet.

[0010] The present invention uses an imiquimod-induced psoriasis mouse model to study the effect of pyruvate on preventing and treating psoriasis and finds that pyruvate can protect the imiquimod-induced psoriasis mouse model, reduce the severity of skin lesions, and improve tissue morphology. The specific experimental method is as follows. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 These are photos of skin lesions on the back of mice in the blank control group (CON), model control group (IMQ), calcipotriol-betamethasone positive control group (CB), obacillus ketone low-dose group (OBA-L) and obacillus ketone high-dose group (OBA-H).

[0012] Figure 2 This is the PASI score curve of the skin lesion severity index of mice in the blank control group (CON), model control group (IMQ), calcipotriol-betamethasone positive control group (CB), obacillus ketone low-dose group (OBA-L) and obacillus ketone high-dose group (OBA-H).

[0013] Figure 3 These are the microphotographs of HE-stained sections of the blank control group (CON), model control group (IMQ), calcipotriol-betamethasone positive control group (CB), obacillus ketone low-dose group (OBA-L) and obacillus ketone high-dose group (OBA-H). DETAILED DESCRIPTION

[0014] 1. Effect Experiment Example

[0015] 1 Drugs and reagents

[0016] Test sample: 0.3% and 1% 0.3% pyruvate ointment was prepared by adding stearic acid, glyceryl monostearate, liquid paraffin, white vaseline, lanolin and triethanolamine. Imiquimod ointment was purchased from Sichuan Mingxin Pharmaceutical Co., Ltd.

[0017] Experimental animals: 30 BalB / C mice, male, weighing 18-22 g, purchased from Guangdong Medical Animal Experiment Center;

[0018] 2 Experimental methods

[0019] 2.1 Experimental groups and drug administration

[0020] Thirty male BalB / C mice weighing 18-22g were randomly divided into 5 groups, 6 mice in each group, namely, blank control group, model control group, calcipotriol-betamethasone positive control group, high-dose imiquimod group and low-dose imiquimod group. Except for the blank control group, the other groups were applied with 5% imiquimod ointment every morning; the model control group was applied with blank cream base every afternoon, and the high- and low-dose imiquimod groups were applied with 0.3% and 1% imiquimod cream, respectively.

[0021] 2.2 Imiquimod-induced psoriasis model in mice:

[0022] The mouse psoriasis model was induced by imiquimod. The hair on the back of the mouse was shaved one day before the experiment to form an area of ​​2 cm × 3 cm. 5% imiquimod ointment (62.5 mg) was evenly applied to the back skin of the mouse once a day for 6 consecutive days to create a psoriasis mouse model. The modeling was stopped on the 7th day, and the mouse was killed by cervical vertebrae dislocation. The back lesion skin of 0.5 cm × 0.5 cm was taken, fixed with 4% paraformaldehyde, embedded in paraffin, and set aside.

[0023] 2.3 Scoring of psoriasis-like skin lesion area and disease severity in mice:

[0024] Psoriasis area and severity index (PASI): After the start of IMQ modeling and before IMQ modeling every day, the PASI score of the mouse back was recorded, that is, the erythema, scaling, and skin infiltration and thickening on the back of the mouse were observed and scored, with each item ranging from 0 to 4 points, for a total of 12 points.

[0025] 2.4 Histopathological observation of mouse skin lesions:

[0026] HE staining is a method of dyeing different substances in the slice into different colors under the action of different dyes, and then observing various structures in the tissue through an optical microscope. It is the most common staining and can help diagnose the degree of skin lesions.

[0027] Pathological histological operations in skin lesion tissue include sampling and fixation, dehydration and transparency, wax immersion and embedding, sectioning and pasting, dewaxing and staining, HE staining, dehydration and transparency, and sealing.

[0028] 2.5 Statistical methods:

[0029] The results were expressed as mean ± standard error (Mean ± SEM) and analyzed using SPSS17.0 statistical software. The differences among the groups were compared using one-way ANOVA (Dunnett's T3 without assuming homogeneity of variance). P < 0.05 indicated a statistically significant difference.

[0030] 3 Results:

[0031] 3.1 Effect of pyruvate on skin lesions in imiquimod-induced psoriasis mouse model

[0032] After the last administration, the skin lesions on the back of mice were as follows: Figure 1 The PASI score results are shown in Figure 2 As shown. The backs of mice in the blank group were smooth and without erythema, indicating no scales and no thickening. Compared with the blank group, the PASI score of the model group increased significantly, the number of skin lesions on the back of mice increased, the skin infiltration and thickening, the color of the lesions was bright red to purple red, the lesions were covered with scales, the scales were thick and layered, and there was a small amount of shedding. Compared with the model group, the PASI score decreased, and the lesions of mice in the drug-treated group still had scales, but the scales showed a decreasing trend compared with the model, and the thickening of the lesions was also improved, indicating that psoralen had a protective effect on mice with psoriasis induced by imiquimod.

[0033] 3.2 Effect of pyruvate on the histomorphology of imiquimod-induced skin lesions in mice

[0034] HE staining showed that the structure Figure 3 Compared with the blank group, the model group showed parakeratosis, increased number of epidermal spinous cells, and thickened spinous cell layer, similar to psoriasis-like pathological changes, indicating that the model was successfully established; after treatment with phellodendron, the epidermal cortex was relatively flat, the number of parakeratotic cells was significantly reduced, and the thickening was lower than that of the model group, indicating that phellodendron could improve the psoriasis-like effect of imiquimod-induced mice.

[0035] 4 Conclusion

[0036] The results showed that berberine could significantly reduce the skin lesions and PASI scores on the back of mice and improve the morphology of skin lesion tissue, indicating that berberine has a good preventive and therapeutic effect on psoriasis.

[0037] 2. Drug Preparation Example

[0038] Example 1: (Gel)

[0039] Take 10 g of pyruvate ketone, add 10 mL of soybean oil to dissolve it, add it to 10 g of carbomer soaked in 500 mL of water and mix well, add distilled water to 1000 g, stir well and add triethanolamine to adjust the pH value to about 10 to obtain 1% pyruvate ketone gel.

[0040] Example 2: (Ointment)

[0041] Take 1000 mg of chicoric acid, add 1000 mg of citric acid, 500 mg of sodium citrate, 1800 mg of sodium chloride, add 1000 ml of water for injection, stir to dissolve, sterilize and filter, fill, and sterilize with circulating steam at 100°C for 15 minutes to make 2 mg / 2 ml injection for injection.

[0042] Take 10g of berberine, add 120g of stearic acid, 35g of glyceryl monostearate, 60g of liquid paraffin, 10g of vaseline, and 50g of lanolin in a container, heat it in a water bath to 75°C, and stir well; add distilled water up to 725g, heat it in a water bath to 75°C, stir well, slowly pour it into the oil phase such as stearic acid, stir well until emulsified, and cool to obtain 1% berberine ointment.

[0043] Example 3: (Capsules)

[0044] Take 500 mg of phellodendron ketone and mix it thoroughly with 4000 mg of microcrystalline cellulose, 500 mg of sodium carboxymethyl starch, 400 mg of sodium lauryl sulfate and other auxiliary materials, use roller compaction method to dry granulate, and then mix it with appropriate amount of magnesium stearate, fill it into 3# hollow capsules, and make capsules with a specification of 10 mg / capsule for oral use.

[0045] Example 4: (Tablet)

[0046] Take 500 mg of berberine, 4000 mg of starch, 200 mg of cross-linked PVP, and 300 mg of sodium carboxymethyl starch, mix them evenly, use 75% ethanol solution of 5% PVP as a binder, make a soft material, granulate with an 18-mesh sieve, dry at 60°C for 1 hour, add appropriate amount of talcum powder to 20-mesh granules, mix well, and press into tablets with a specification of 10 mg / tablet for oral use.

Claims

1. The use of pyruvate in the preparation of a drug for preventing and treating psoriasis, wherein: The chemical structure of the bactericidal ketone is shown in the following formula (I):

2. The use according to claim 1, characterized in that: The medicine consists of pyruvate ketone and medically acceptable auxiliary materials, wherein the mass percentage of pyruvate ketone in the medicine is 0.3% to 15%.

3. The use according to claim 2, characterized in that: The medicine is a gel, an ointment, a capsule or a tablet.

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