阅读说明：本技术 一种药物制剂及其应用 (Pharmaceutical preparation and application thereof ) 是由 兰晓鸥 于 2021-09-01 设计创作，主要内容包括：本发明公开了一种药物制剂及其应用,具体涉及药物制剂领域。所述制剂的有效成分包括紫草素、月见草油和乙氧苯柳胺。所述制剂在制备治疗皮肤病的药物中应用。所述制剂将紫草素、月见草油和乙氧苯柳胺等化学成分制备成一种皮肤外用制剂,可以有效发挥紫草素、月见草油、乙氧苯柳胺的药用功能。本发明的药物制剂对治疗皮炎、湿疹、痤疮、皲裂、银屑病等皮肤病均有良好的效果,动物干预实验可见,本发明的药物制剂对于预防部分皮肤科疾病同样具有一定效果,可为临床预防/治疗皮炎、湿疹、痤疮、皲裂、银屑病等皮肤病提供一种安全、有效的外用药物新选择。(The invention discloses a pharmaceutical preparation and application thereof, and particularly relates to the field of pharmaceutical preparations. The effective components of the preparation comprise alkannin, evening primrose oil and ethoxybenzene willow amine. The preparation is applied to the preparation of medicines for treating skin diseases. The preparation is prepared from chemical components such as alkannin, evening primrose oil, ethoxybenzene willow amine and the like into a skin external preparation, and can effectively exert the medicinal functions of the alkannin, the evening primrose oil and the ethoxybenzene willow amine. The pharmaceutical preparation has good effects on treating skin diseases such as dermatitis, eczema, acne, rhagadia, psoriasis and the like, and animal intervention experiments show that the pharmaceutical preparation has certain effects on preventing partial skin diseases, and can provide a safe and effective new choice of external drugs for clinically preventing/treating the skin diseases such as dermatitis, eczema, acne, rhagadia, psoriasis and the like.)

1. A pharmaceutical preparation is characterized in that the effective components of the preparation comprise alkannin, evening primrose oil and ethoxybenzene willow amine.

2. The pharmaceutical preparation of claim 1, wherein the preparation further comprises pharmaceutical preparation common adjuvants; the common adjuvants of the pharmaceutical preparation are one or more of cetearyl glucoside, glyceryl stearate, stearyl alcohol, liquid paraffin, methyl paraben, ethylparaben, disodium EDTA, glycerol, distilled water, sodium metabisulfite, vaseline or 6-di-tert-butyl-4-methylphenol.

3. The pharmaceutical preparation according to claim 2, wherein the preparation comprises the following components in percentage by mass: alkannin 0.0001-5%; 0.01-30% of evening primrose oil; 0.01-30% of ethoxybenzene willow amine and 35-99% of common auxiliary materials of medicinal preparations.

4. The pharmaceutical formulation of claim 3, wherein the formulation is in the form of an oil, cream, ointment, gel, lotion, plaster, paste, or film.

5. The pharmaceutical formulation of claim 4, wherein the cream is prepared by a method comprising:

step one, preparation of oil phase

Placing alkannin, oleum Oenotherae Erythrosepalae, cetearyl glucoside, glyceryl stearate, stearyl alcohol, and liquid paraffin in a container, heating to 80 deg.C for melting, and adding 6-di-tert-butyl-4-methylphenol while stirring;

step two, preparation of water phase

Putting phenelzine, methyl hydroxybenzoate, ethylparaben, EDTA disodium, glycerol and distilled water in a container, and heating to 80 deg.C;

and step three, adding the water phase in the step two into the oil phase in the step one, stirring, carrying out an emulsification reaction for 3-5 minutes, stopping the emulsification when the temperature is reduced to 70 ℃, rapidly cooling to 45 ℃, adding sodium pyrosulfite, slowly stirring uniformly, and cooling to 30 ℃ to obtain the cream.

6. The pharmaceutical preparation according to claim 5, wherein the preparation comprises the following components in percentage by mass: 0.0001-5% of alkannin, 0.01-30% of evening primrose oil, 3% of cetearyl glucoside, 2% of glycerol stearate, 3% of octadecanol, 6% of liquid paraffin, 0.01% of 6-di-tert-butyl-4-methylphenol, 0.01-30% of ethoxybenzene willow amine, 0.1% of methyl hydroxybenzoate, 0.1% of ethylparaben, 0.05% of disodium EDTA, 10% of glycerol, 0.05% of sodium pyrosulfite and 50-75.6699% of distilled water.

7. The pharmaceutical formulation of claim 4, wherein the ointment is prepared by a method comprising:

firstly, sufficiently mixing the ethoxybenzene willow amine, the alkannin and the evening primrose oil as standby raw materials; heating vaseline to 80 deg.C, adding 6-di-tert-butyl-4-methylphenol, dissolving, adding into the above materials, stirring, grinding, and condensing to obtain the ointment.

8. The pharmaceutical preparation according to claim 7, wherein the preparation comprises the following components in percentage by mass: 0.0001-5% of alkannin, 0.01-30% of evening primrose oil, 0.01-30% of ethoxybenzene willow amine, 50-99.9699% of vaseline and 0.01% of 6-di-tert-butyl-4-methylphenol.

9. Use of a formulation according to any one of claims 1 to 8 in the manufacture of a medicament for the treatment of a skin disorder.

10. Use of a formulation according to claim 9, wherein the skin disorder comprises dermatitis, eczema, acne, chapping or psoriasis.

Technical Field

The invention relates to the field of pharmaceutical preparations, in particular to a pharmaceutical preparation and application thereof.

Background

The lithospermum erythrorhizon has sweet, salty and cold natures, enters heart and liver channels, has the functions of cooling blood and activating blood, clearing away heat and toxic materials, resisting inflammation and inhibiting immunity, and has the functions of inhibiting growth and promoting apoptosis on tumor cells. In traditional Chinese medicine, lithospermum is often processed into alkannin which is used for detoxifying and promoting eruption, activating blood and cooling blood, and is mainly used for treating symptoms such as fire burn, measles imperviousness, macula purple black, blood heat and toxin excess, heat accumulation constipation and the like.

The evening primrose oil is grease extracted from seeds of evening primrose, the main functional component of the evening primrose oil is gamma-linolenic acid which is also called vitamin F, the substance has obvious anti-inflammatory effect on autoimmune inflammation, and simultaneously the evening primrose oil is also an excellent humectant which can be used for drying skin and has good anti-skin aging effect.

Ethoxybenzene salicylamide (molecular formula: C)₈H₁₁NO) is a non-steroidal anti-inflammatory and anti-allergic drug, which can effectively reduce the permeability of capillary vessels by inhibiting the release of allergic mediators (such as histamine, 5-hydroxytryptamine, prostaglandin E1, and the like) from mast cells; inhibiting inflammatory swelling and granulation tissue proliferation during inflammatory proliferation; thereby realizing the functions of anti-inflammation, anti-allergy and itching relieving.

During the research process, the inventor finds that the alkannin can effectively inhibit the phenomenon of keratinocyte hyperproliferation (relevant papers are published in International Immunopharmacology,2019,72.If value: 3.9; and Molecular Medicine Reports,2020,22.If value: 2.1); the ethoxybenzene salicylamide has good therapeutic effect on aseptic inflammatory reaction. Previous researches find that the single use of the ethoxybenzene willow amine has slow effect, and other medicines are often required to be combined for treating the acute stage of diseases. Alkannin can effectively inhibit excessive proliferation of keratinocyte due to its less side effects, and has rapid action. At present, in the disclosed Chinese patent medicines, chemical medicines and medicinal compositions, no patent of dermatological medicinal preparations containing alkannin, evening primrose oil and ethoxybenzene willow amine is disclosed.

Currently, glucocorticoid or antibiotic medicines are most preferred in clinical treatment of skin diseases such as chronic eczema, neurodermatitis, acne, psoriasis and the like. However, if the medicine is used for a long time, various side effects such as skin atrophy, pigment abnormality, telangiectasia and the like are generated; or the drug resistance is formed, so that the new substitute drug is more clinically needed; even if the medicine is not hormone or antibiotic medicine, such as calcipotriol, tacrolimus and the like, the medicine still can generate certain stimulation to the affected part or the surrounding skin, and side effects such as transient blood calcium rise and the like can also occur; although there are currently data showing: the ethoferoxil ointment can be used for treating skin diseases such as acne and eczema by singly using the ethoferoxil ointment, but no report of using the ethoferoxil to treat psoriasis exists at present.

Disclosure of Invention

Therefore, the invention provides a medicinal preparation and application thereof, and aims to solve the problems of poor treatment effect, large side effect and the like of the existing medicaments for treating skin diseases such as psoriasis and the like.

In order to achieve the above purpose, the invention provides the following technical scheme:

according to one aspect of the present invention, there is provided a pharmaceutical preparation, the active ingredients of which comprise alkannin, evening primrose oil and ethoxybenzene willow amine.

Furthermore, the preparation also comprises common auxiliary materials of medicinal preparations; the common auxiliary materials of the pharmaceutical preparation are one or more of a surfactant, an antioxidant, a preservative, a flavoring agent, a coloring agent, a synthetic macromolecular compound or a natural macromolecular compound.

Furthermore, the common auxiliary materials of the medicinal preparation are one or more of cetearyl glucoside, glycerol stearate, stearyl alcohol, liquid paraffin, methyl paraben, ethyl paraben, disodium EDTA, glycerol, distilled water, sodium metabisulfite, vaseline or 6-di-tert-butyl-4-methylphenol.

Further, the preparation comprises the following components in percentage by mass: alkannin 0.0001-5%; 0.01-30% of evening primrose oil; 0.01-30% of ethoxybenzene willow amine and 35-99% of common auxiliary materials of medicinal preparations.

Furthermore, the preparation formulation comprises external preparations such as oil, cream, ointment, gel, lotion, plaster, paste or film coating agent and the like.

Further, the preparation method of the cream comprises the following steps:

step one, preparation of oil phase

Placing alkannin, oleum Oenotherae Erythrosepalae, cetearyl glucoside, glyceryl stearate, stearyl alcohol, and liquid paraffin in a container, heating to 80 deg.C for melting, and adding 6-di-tert-butyl-4-methylphenol while stirring;

step two, preparation of water phase

Putting phenelzine, methyl hydroxybenzoate, ethylparaben, EDTA disodium, glycerol and distilled water in a container, and heating to 80 deg.C;

and step three, adding the water phase in the step two into the oil phase in the step one, stirring, carrying out an emulsification reaction for 3-5 minutes, stopping the emulsification when the temperature is reduced to 70 ℃, rapidly cooling to 45 ℃, adding sodium pyrosulfite, slowly stirring uniformly, and cooling to 30 ℃ to obtain the cream.

Further, the preparation comprises the following components in percentage by mass: 0.0001-5% of alkannin, 0.01-30% of evening primrose oil, 3% of cetearyl glucoside, 2% of glycerol stearate, 3% of octadecanol, 6% of liquid paraffin, 0.01% of 6-di-tert-butyl-4-methylphenol, 0.01-30% of ethoxybenzene willow amine, 0.1% of methyl hydroxybenzoate, 0.1% of ethylparaben, 0.05% of disodium EDTA, 10% of glycerol, 0.05% of sodium pyrosulfite and 50-75.6699% of distilled water.

Further, the preparation method of the ointment comprises the following steps:

firstly, sufficiently mixing the ethoxybenzene willow amine, the alkannin and the evening primrose oil as standby raw materials; heating vaseline to 80 deg.C, adding 6-di-tert-butyl-4-methylphenol, dissolving, adding into the above materials, stirring, grinding, and condensing to obtain the ointment.

Further, the preparation comprises the following components in percentage by mass: 0.0001-5% of alkannin, 0.01-30% of evening primrose oil, 0.01-30% of ethoxybenzene willow amine, 50-99.9699% of vaseline and 0.01% of 6-di-tert-butyl-4-methylphenol. According to another aspect of the invention there is provided the use of a formulation as described above in the manufacture of a medicament for the treatment of a skin disorder.

Further, the skin disease includes dermatitis, eczema, acne, chapping or psoriasis.

The invention has the following advantages:

the ethoferoxil does not contain steroid components, so adverse reactions of glucocorticoid do not occur, and the anti-inflammatory effect is excellent; alkannin has effects of cooling blood, promoting blood circulation, clearing away heat and toxic materials, relieving inflammation, inhibiting immunity, inhibiting growth of tumor cells, and promoting apoptosis; the evening primrose oil has an obvious anti-inflammatory effect on autoimmune inflammation, is an excellent humectant, can be used for drying skin and has a good effect of resisting skin aging; the external preparation prepared from the alkannin, the evening primrose oil, the ethoxybenzene willow amine and common auxiliary materials of the medicinal preparation according to a certain proportion has good effect on preventing/treating psoriasis mouse models; and the three main components, two of which are pure plant extracts, and one of which is an anti-inflammatory drug without steroid components, are almost nonirritating, nontoxic and side-effect-free, can be administrated to the face and children, does not have the side effect of glucocorticoid or antibiotic drugs after long-term administration, and is safe and reliable. Therefore, the external preparation has better clinical application prospect.

The invention prepares the chemical components of the alkannin, the evening primrose oil, the ethoxybenzene willow amine and the like into the skin external preparation, and can more effectively exert the medicinal functions of the alkannin, the evening primrose oil and the ethoxybenzene willow amine. Tests show that the effect of the composition is far greater than that of any one of the components used alone or any two of the components used in combination within the effective concentration range.

The medicinal preparation has good effects on treating skin diseases such as dermatitis, eczema, acne, rhagadia, psoriasis and the like, and animal experiments show that the medicinal preparation has certain effects on preventing skin diseases, and can provide a safe and effective new choice of external medicaments for clinically preventing/treating the skin diseases such as dermatitis, eczema, acne, rhagadia, psoriasis and the like.

Animal experiments show that the medicinal preparation has good curative effect on treating/preventing psoriasis.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below. It should be apparent that the drawings in the following description are merely exemplary, and that other embodiments can be derived from the drawings provided by those of ordinary skill in the art without inventive effort.

The structures, ratios, sizes, and the like shown in the present specification are only used for matching with the contents disclosed in the specification, so that those skilled in the art can understand and read the present invention, and do not limit the conditions for implementing the present invention, so that the present invention has no technical significance, and any structural modifications, changes in the ratio relationship, or adjustments of the sizes, without affecting the functions and purposes of the present invention, should still fall within the scope of the present invention.

FIG. 1 is a graph of the results of the intervention effect of the cream A, B containing alkannin, evening primrose oil and ethoxybenzene willow amine on the formation of an imiquimod-induced psoriasis mouse model, the PASI scores among groups every day and the change trend; wherein A is the score of the thickness of the skin lesion of the mouse, B is the score of the condition of the erythema of the skin of the mouse, C is the score of the condition of the scale of the mouse, D is the score of the thickness of the skin lesion of the mouse, the score of the condition of the erythema of the skin of the mouse and the score of the condition of the scale of the mouse, and the scores of the three are added to obtain a total score;

FIG. 2 is a graph showing the results of the therapeutic effect of ointment B containing shikonin, evening primrose oil and ethoxybenzene willow amine on the mouse model of psoriasis induced by imiquimod, and the PASI scores and the change trend among groups every day; wherein, A is the score of the thickness of the skin lesion of the mouse, B is the score of the condition of the erythema of the skin of the mouse, C is the score of the condition of the scaling of the mouse, D is the score of the thickness of the skin lesion of the mouse, the score of the condition of the erythema of the skin of the mouse and the score of the condition of the scaling of the mouse, and the total score obtained by adding the scores of the three is obtained;

FIG. 3 is a graph showing the results of the intervention effect of ointment B containing shikonin, evening primrose oil and ethoxybenzene willow amine and ointment E containing a single component (shikonin) on the formation of an imiquimod-induced psoriasis mouse model, and the PASI scores and the change trend among groups every day; wherein, A is the score of the thickness of the skin lesion of the mouse, B is the score of the condition of the erythema of the skin of the mouse, C is the score of the condition of the scaling of the mouse, D is the score of the thickness of the skin lesion of the mouse, the score of the condition of the erythema of the skin of the mouse and the score of the condition of the scaling of the mouse, and the total score obtained by adding the scores of the three is obtained;

FIG. 4 is a comparison chart of the skin of each group of mice after 8 days in Experimental example 1 of the present invention; wherein, A is the skin condition map of the mice in the 1 st group, B is the skin condition map of the mice in the 2 nd group, C is the skin condition map of the mice in the 3 rd group, and D is the skin condition map of the mice in the 4 th group.

Detailed Description

The present invention is described in terms of particular embodiments, other advantages and features of the invention will become apparent to those skilled in the art from the following disclosure, and it is to be understood that the described embodiments are merely exemplary of the invention and that it is not intended to limit the invention to the particular embodiments disclosed. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1 preparation of a pharmaceutical formulation containing alkannin, evening primrose oil, and ethoxybenzene salicylamide the procedure for preparing the pharmaceutical formulation is as follows:

step one, preparation of oil phase

Oil phase: placing 0.0125g of alkannin, 4g of evening primrose oil, 3g of cetearyl glucoside, 2g of glycerol stearate, 3g of octadecanol and 6g of liquid paraffin into a proper container, heating to 80 ℃ to melt, and then adding 0.01g of 6-di-tert-butyl-4-methylphenol;

step two, preparation of water phase

Putting 1.5g of ethoxybenzene willow amine, 0.1g of methyl hydroxybenzoate, 0.1g of ethylparaben, 0.05g of EDTA disodium, 10g of glycerol and 70.2g of distilled water into a proper container, and heating to 80 ℃;

and step three, injecting the water phase into the oil phase, stirring and carrying out emulsion reaction for about 3-5 minutes, stopping emulsification when the temperature is reduced to 70 ℃, rapidly cooling to 45 ℃, adding 0.05g of sodium pyrosulfite, slowly stirring uniformly, and cooling to 30 ℃ to obtain the cream A containing the alkannin, the evening primrose oil and the ethoxybenzene willow amine.

Example 2 preparation of a pharmaceutical formulation containing alkannin, evening primrose oil, and ethoxybensalamine the pharmaceutical formulation was prepared by the following steps:

step one, preparation of oil phase

Oil phase: placing 0.025g of alkannin, 8g of evening primrose oil, 3g of cetearyl glucoside, 2g of glyceryl stearate, 3g of octadecanol and 6g of liquid paraffin into a proper container, heating to 80 ℃ to melt, and then adding 0.01g of 6-di-tert-butyl-4-methylphenol;

step two, preparation of water phase

Putting 3g of phenelzine, 0.1g of methyl-p-hydroxybenzoate, 0.1g of ethylparaben, 0.05g of EDTA disodium, 10g of glycerol and 64.72g of distilled water into a proper container, and heating to 80 ℃;

and step three, injecting the water phase into the oil phase, stirring and carrying out emulsion reaction for about 3-5 minutes, stopping emulsification when the temperature is reduced to 70 ℃, rapidly cooling to 45 ℃, adding 0.05g of sodium pyrosulfite, slowly stirring uniformly, and cooling to 30 ℃ to obtain the cream B containing the alkannin, the evening primrose oil and the ethoxybenzene willow amine.

EXAMPLE 3 preparation of a pharmaceutical formulation containing Shikonin, evening primrose oil and Oxyphenylsalicylic acid

Mixing and grinding 1g of ethoxybenzene willow amine, 0.02g of alkannin and 4g of evening primrose oil to obtain standby raw materials; heating vaseline oil 94.96g to 80 deg.C, adding 6-di-tert-butyl-4-methylphenol 0.02g, dissolving, adding into the above materials, stirring, grinding, and condensing to obtain ointment A containing alkannin, oleum Oenotherae Erythrosepalae, and phenelzine.

EXAMPLE 4 preparation of a pharmaceutical formulation containing Shikonin, evening primrose oil and Oxyphenylsalicylic amine

Firstly, 4g of phenelzine, 0.04g of alkannin and 8g of evening primrose oil are mixed and ground into standby raw materials; heating vaseline oil 87.94g to 80 deg.C, adding 6-di-tert-butyl-4-methylphenol 0.02g, dissolving, adding into the above raw materials, stirring, grinding, and condensing to obtain ointment B containing alkannin, oleum Oenotherae Erythrosepalae, and phenelzine.

EXAMPLE 5 preparation of a pharmaceutical formulation containing Shikonin, evening primrose oil, Ethoxybenzene Salix amine

Mixing 5g of ethoxybenzene willow amine, 0.1g of alkannin and 10g of evening primrose oil and grinding into a standby raw material; heating vaseline oil 84.88g to 80 deg.C, adding 6-di-tert-butyl-4-methylphenol 0.02g, dissolving, adding into the above materials, stirring, grinding, and condensing to obtain ointment C containing alkannin, oleum Oenotherae Erythrosepalae, and phenelzine.

EXAMPLE 6 preparation of a pharmaceutical formulation containing Shikonin, evening primrose oil, and Oxyphenylsalicylic acid

Mixing and grinding 10g of ethoxybenzene willow amine, 0.5g of alkannin and 30g of evening primrose oil to obtain standby raw materials; and heating 59.38g of vaseline oil to 80 ℃, adding 0.02g of 6-di-tert-butyl-4-methylphenol, dissolving, adding the dissolved vaseline oil into the standby raw materials, stirring, grinding, and condensing to obtain an ointment D containing alkannin, evening primrose oil and ethoxybenzene willow amine.

Comparative example 1 preparation of a cream containing Shikonin alone

Adding 1g of shikonin into 98.98g of vaseline oil, heating to 80 ℃, adding 0.02g of 6-di-tert-butyl-4-methylphenol, dissolving, adding into the standby raw materials, stirring, grinding, and condensing to obtain an ointment E only containing shikonin.

Experimental example 1 intervention experiment of different contents of alkannin, evening primrose oil and phenetidine in cream on imiquimod-induced psoriasis mice

First, establishment of psoriasis model of mouse

Balb/c mice 20, shaved back hair, exposed about 2cm by 3cm area for modeling. All mice were randomly divided into 1, 2, 3, 4 groups of 5 mice each. Group 4 was left untreated as a placebo. All mice in groups 1, 2 and 3 are externally coated with 50mg of imiquimod cream with the concentration of 5% every morning in the modeling area, and after the mice are applied for 6 hours, the mice in group 1 are externally coated with 50mg of cream A in the modeling area; the modeled zone of group 2 mice was given an external application of 50mg cream B, group 3 mice were given no drug intervention, and each group of mice was sacrificed by decapitation after 8 days of continuous dosing.

The area of psoriatic lesions and the severity of the disease (PASI) score were recorded for each group of mice: regularly photographing every day to record the skin damage condition of each group of mice, scoring erythema, scale and infiltration thickening degree of the skin damage of the mice according to the PASI scoring standard, and adding the scores of the three to obtain a total score.

The PASI scoring criteria for each group of mice are as follows: 0: none; 1: mild; 2: moderate; 3: (ii) severe; 4: is extremely severe.

And calculating an average value according to the scores of the mice in each group, drawing a score trend curve, and evaluating the psoriasis sample skin lesion forming condition of the mice in each group, wherein the higher the PASI score is, the more serious the skin lesion is.

The statistical method comprises the following steps: SPSS 16.0 software for statistical analysis, data measurementAnd (3) representing that the change of observation indexes among the same groups adopts one-factor variance analysis, and the two-two multiple comparison adopts LSD-t test. The difference is statistically significant when P is less than 0.05. The results of the experiment are shown in FIG. 1, and the degree of skin surface damage of each group of mice is shown in FIG. 4.

Group 4 mice were blank control groups, and the mice in this group had smooth skin on the back. The group 3 mice were animal model groups and were not intervened with other drugs, and they developed erythema and a small amount of scales after topical application of imiquimod cream to the epidermis. As the erythema, the infiltration degree and the surface scale increase with the lapse of time, the punctate bleeding phenomenon can be seen when the scale is scraped; erythema, scaling and infiltration thickening were most evident on day 8. The skin surface of the mice modeled after the 1 st model mouse interfered with the cream A and the 2 nd model mouse interfered with the cream B has the erythema and the scaling degree which are not as good as those of the 3 rd model mouse. The difference in PASI scores between groups was statistically significant (F: 229.182, P < 0.01, n: 5) and the difference between two pairs of groups was statistically significant (P < 0.01). Group 2 mice that were intervened with high concentration of cream B had lighter erythema and fewer scales on the epidermis than group 1 mice that were intervened with low concentration of cream a. Therefore, the cream containing the alkannin, the evening primrose oil and the ethoxybenzene willow amine can effectively prevent the imiquimod from inducing the psoriasis mouse model. As can be seen in FIG. 4, using the mice of groups 1 and 2 of the present invention, the body surface was dark in color with no significant swelling, indicating that the present invention was not irritating. The external preparation is determined by the raw material medicaments, and has no toxic or side effect after long-term use.

Experimental example 2 study on therapeutic effect of ointment B containing alkannin, evening primrose oil and ethoxybenzene salicylamide on psoriasis mice

First, establishment of psoriasis model of mouse

Balb/c mice 20, shaved back hair, exposed about 2cm by 3cm area for modeling. All mice were randomly divided into 1, 2, 3, 4 groups of 5 mice each. Group 4 was left untreated as a placebo. All mice in groups 1, 2, and 3 were treated with 5% imiquimod cream 50mg daily eleven points on a modeled area to create a psoriasis mouse model.

Group 4 was left untreated as a placebo. All mice in groups 1, 2 and 3 were administered for 8 consecutive days. Group 1 mice were not given treatment starting on day 8; the mice in group 2 were topically applied with 50mg of ointment B obtained in example 3; the mice in group 3 were externally applied with 50mg of calcipotriol cream. The treatment is carried out for 3 days in total, the skin damage condition of each group of mice is recorded by photographing at 18 points every day, and the improvement condition of the psoriasis-like skin damage of each group of mice is evaluated. Scoring erythema, scale and infiltration thickening degree of the skin lesion of the mouse according to the PASI scoring standard, and adding the scores of the three to obtain a total score. The results of the experiment are shown in FIG. 2.

Group 4 mice were blank control groups, and the mice in this group had smooth skin on the back. The mice in groups 1, 2 and 3 are externally coated with imiquimod cream for 8 days to induce erythema and a large amount of thick-layer scale; the spot bleeding phenomenon can be seen when the scales are scraped; i.e. typical psoriasis-like lesions. After 3 days of treatment, the degree of erythema and skin lesion infiltration was significantly reduced, the scales were significantly reduced, the skin lesions were significantly improved in the group 2 and the group 3, and the difference in PASI scores between the two groups was not statistically significant (P0.069, P > 0.05, n 5), while the difference in PASI scores between the other two groups was statistically significant (F27.281, P < 0.01, n 5). Untreated mice in group 1 had far less skin lesions than mice in groups 2 and 3. The result shows that the ointment B containing the alkannin, the evening primrose oil and the ethoxybenzene willow amine has a treatment effect on psoriasis-like skin lesions, the action effect is not inferior to that of a classic medicine calcipotriol cream for treating psoriasis, but the side effect is lower than that of the calcipotriol cream due to the characteristics of raw material medicines.

Experimental example 3 comparative experiment of the effect of the ointment B containing shikonin, evening primrose oil and ethoxybenzene willowamide on the formation of an imiquimod-induced psoriasis mouse model with the ointment E of the single ingredient (shikonin) of comparative example 1

Balb/c mice 20, shaved back hair, exposed about 2cm by 3cm area for modeling. All mice were randomly divided into 1, 2, 3, 4 groups of 5 mice each. Group 4 was not treated as a placebo. All mice in groups 1, 2 and 3 were externally coated with 5% imiquimod cream 50mg in the modeling area twelve am each day, and after 6 hours of administration, the mice in group 1 were externally coated with 50mg of ointment B obtained in example 3 in the modeling area; the modeled zone of group 2 mice was given an external 50mg of ointment E, group 3 mice were given no drug intervention, and each group of mice was sacrificed by decapitation after 8 consecutive days of dosing. The area of psoriatic lesions and the severity of the disease (PASI) score were recorded for each group of mice: regularly photographing every day to record the skin damage condition of each group of mice, scoring erythema, scale and infiltration thickening degree of the skin damage of the mice according to the PASI scoring standard, and adding the scores of the three to obtain a total score. The results of the experiment are shown in FIG. 3.

Group 4 mice were blank control groups, and the mice in this group had smooth skin on the back. The group 3 mice were animal model groups and were not intervened with other drugs, and they developed erythema and a small amount of scales after topical application of imiquimod cream to the epidermis. As the erythema, the infiltration degree and the surface scale increase with the lapse of time, the punctate bleeding phenomenon can be seen when the scale is scraped; erythema, scaling and infiltration thickening were most evident on day 8. Intervention in the case of skin lesion thickness: there was no significant difference in skin lesion changes between days 1-3 in group 1 and group 2 mice, and from day 4, group 2 ointment E had less intervention in skin lesion thickness than group 1 ointment B. Intervention in the case of erythema of skin lesions: ointment E of group 2 did not interfere as well with erythema of the lesion as ointment B of group 1. Intervention in the case of scaling of skin lesions: there was no significant difference in the lesion scale intervention between group 1 and group 2 mice on days 1-2, and from day 3, ointment E of group 2 was less effective in the lesion scale intervention than ointment B of group 1. The difference in PASI scores between groups was statistically significant (F: 229.182, P < 0.01, n: 5) and the difference between two pairs of groups was statistically significant (P < 0.01). Although the content of the shikonin component in the component of ointment E was 25 times that of ointment B, group 1 mice that intervened with ointment B had lighter erythema, less scaling, and better intervention in psoriatic lesions in the epidermis than group 2 mice that intervened with ointment E. Therefore, the ointment B containing the alkannin, the evening primrose oil and the ethoxybenzene willow amine has better anti-inflammatory and anti-proliferative effects and better intervention effect on the formation of psoriasis-like skin lesions, and has certain potential for preventing clinical psoriasis.

As can be seen from the results of experimental examples 1 and 3, the skin external preparation containing the alkannin, the evening primrose oil and the ethoxybenzene willow amine has certain intervention effect on the formation process of a psoriasis mouse model, which indicates that the external preparation has the potential for clinically preventing the psoriasis; the results of the experimental example 2 show that the external preparation containing the alkannin, the evening primrose oil and the ethoxybenzene willow amine has the treatment effect on psoriasis-like skin lesions, the effect is not inferior to that of the classic medicine of the calcipotriol cream for treating psoriasis, but the side effect is lower than that of the calcipotriol cream. The results of experiment example 3 show that the pharmaceutical preparation containing shikonin, evening primrose oil and ethoxyphenyl willow amine has better effect than the pharmaceutical preparation containing shikonin alone. In all the experiments, the body weight of each group of mice has no obvious difference (P is more than 0.5) before and after the experiment, which indicates that the product of the invention has no adverse stimulation effect on the growth, development and feeding of the mice. In conclusion, the invention can provide a safe and effective new choice of external medicine for clinically treating skin diseases such as dermatitis, eczema, acne, rhagadia, psoriasis and the like.

Although the invention has been described in detail above with reference to a general description and specific examples, it will be apparent to one skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.