CN113288926A

CN113288926A - Pharmaceutical preparation and application thereof

Info

Publication number: CN113288926A
Application number: CN202110483754.7A
Authority: CN
Inventors: 兰晓鸥
Original assignee: Shenyang Seventh People's Hospital
Current assignee: Shenyang Seventh People's Hospital
Priority date: 2021-04-30
Filing date: 2021-04-30
Publication date: 2021-08-24
Also published as: CN113499356A

Abstract

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 arnebia oil, 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 lithospermum oil, evening primrose oil, ethoxybenzene willow amine and the like into a skin external preparation, and can effectively exert the medicinal functions of the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine. The medicinal preparation has good effects on treating skin diseases such as dermatitis, eczema, acne, psoriasis and the like, and animal intervention experiments show that the medicinal preparation has certain effects on preventing partial skin diseases, and can provide a safe and effective new choice of external medicaments for clinically preventing/treating the skin diseases such as the dermatitis, the eczema, the acne, the psoriasis and the like.

Description

Pharmaceutical preparation and application thereof

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 lithospermum oil 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. The arnebia oil has fewer side effects, can effectively inhibit the hyperproliferation of keratinocytes, and has quick response. At present, in the disclosed Chinese patent medicines, chemical medicines and medicinal combinations, no patent of dermatological medicinal preparations containing lithospermum oil, 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 arnebia oil, 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 pharmaceutical preparation are one or more of cetearyl glucoside, glycerol stearate, stearyl alcohol, liquid paraffin, methyl paraben, ethyl paraben, disodium EDTA, glycerol, purified water, sodium metabisulfite, vaseline or 6-di-tert-butyl-4-methylphenol.

Further, the preparation comprises the following components in percentage by mass: 0.01-90% of lithospermum oil; evening primrose oil 0.01-90%; 0.01-30% of ethoxybenzene willow amine and 0.01-99% of common auxiliary materials of medicinal preparations.

Furthermore, the preparation can be prepared into external preparations such as ointment, cream, ointment, gel, lotion, liniment 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 radix Arnebiae oil, oleum Oenotherae Erythrosepalae, cetearyl glucoside, glyceryl stearate, stearyl alcohol, and liquid paraffin in a container, heating to 78-82 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 purified water in a container, and heating to 78-82 deg.C;

and step three, adding the water phase in the step two into the oil phase in the step one, fully emulsifying at the temperature of 78-82 ℃, uniformly stirring and mixing, cooling to 68-72 ℃ after 5 minutes, adding sodium pyrosulfite when continuing to cool to 48-52 ℃, and cooling to room temperature to obtain the cream.

Further, the preparation comprises the following components in percentage by mass: 1-30% of lithospermum oil, 1-30% of evening primrose oil, 3% of cetearyl glucoside, 2% of glyceryl stearate, 3% of octadecanol, 6% of liquid paraffin, 0.01% of 6-di-tert-butyl-4-methylphenol, 1-10% of ethoxybenzene willow amine, 0.1% of methyl paraben, 0.1% of ethylparaben, 0.05% of disodium EDTA, 10% of glycerol, 0.05% of sodium metabisulfite and 40-72.69% of purified water.

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

grinding the phenelzine into fine powder of 100 meshes, adding the fine powder into mixed oil of the lithospermum oil and the evening primrose oil, and uniformly mixing; heating vaseline to 58-62 ℃, adding the uniformly mixed mixture of the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine, uniformly mixing, adding the 6-di-tert-butyl-4-methylphenol while stirring, uniformly mixing, and cooling to room temperature to obtain the ointment.

Further, the preparation comprises the following components in percentage by mass: 1-30% of lithospermum oil, 1-30% of evening primrose oil, 1-10% of ethoxybenzene willow amine, 30-96.99% 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, 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; the arnebia oil 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 lithospermum oil, 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 the prevention/treatment of the induced psoriasis mice; and the three main components, two of which are pure plant extracts, and one of which is an anti-inflammatory drug without a steroid component, are almost nonirritating, nontoxic and side-effect-free, can be applied 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 lithospermum oil, the evening primrose oil, the ethoxybenzene willow amine and the like into a skin external preparation, and can more effectively exert the medicinal functions of the lithospermum oil, 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, psoriasis and the like, and animal intervention 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 the dermatitis, the eczema, the acne, the 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 showing the results of the intervention effect of the cream containing arnebia oil, evening primrose oil and ethoxybenzene willow amine 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 on the skin of the mouse, C is the score of the recovery condition of the psoriasis 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 on the skin of the mouse and the score of the recovery condition of the psoriasis 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 the salve A containing arnebia oil, 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 on the skin of the mouse, C is the score of the recovery condition of the psoriasis 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 on the skin of the mouse and the score of the recovery condition of the psoriasis 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 the ointment A containing arnebia oil, evening primrose oil and ethoxybenzene willow amine and the ointment of a single component (arnebia oil) 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 on the skin of the mouse, C is the score of the recovery condition of the psoriasis 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 on the skin of the mouse and the score of the recovery condition of the psoriasis 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 Lithospermum erythrorhizon oil, Oenothera biennis oil, and Oxyphenylsalicylic acid

The steps for preparing the pharmaceutical formulation are as follows:

step one, preparation of oil phase

Placing 2.5g of lithospermum oil, 4g 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 +/-2 ℃ to melt, and adding 0.01g of 6-di-tert-butyl-4-methylphenol while stirring;

step two, preparation of water phase

Putting 1.5g of ethoxybenzene willow amine, 0.1g of methyl-p-hydroxybenzoate, 0.1g of ethyl-p-hydroxybenzoate, 0.05g of EDTA disodium, 10g of glycerol and 67.74g of purified water into a proper container, and heating to 80 +/-2 ℃;

and step three, adding the water phase in the step two into the oil phase in the step one, fully emulsifying at the temperature of 80 +/-2 ℃, stirring, uniformly mixing, cooling to 70 +/-2 ℃ after 5 minutes, rapidly cooling to 50 +/-2 ℃, adding 0.05g of sodium pyrosulfite, and cooling to room temperature to obtain the cream A containing the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine.

EXAMPLE 2 preparation of a pharmaceutical formulation containing Lithospermum erythrorhizon oil, Oenothera biennis oil, and Oxyphenylsalicylic acid

The steps for preparing the pharmaceutical formulation are as follows:

step one, preparation of oil phase

Placing 5g of lithospermum oil, 8g of evening primrose oil, 3g of cetearyl glucoside, 2g of glyceryl stearate, 3g of octadecanol and 6g of liquid paraffin in a proper container, heating to 80 +/-2 ℃ for melting, and adding 0.01g of 6-di-tert-butyl-4-methylphenol while stirring;

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 59.74g of purified water into a proper container, and heating to 80 +/-2 ℃;

and step three, adding the water phase in the step two into the oil phase in the step one, fully emulsifying at the temperature of 80 +/-2 ℃, stirring, uniformly mixing, cooling to 70 +/-2 ℃ after 5 minutes, rapidly cooling to 50 +/-2 ℃, adding 0.05g of sodium pyrosulfite, and cooling to room temperature to obtain the cream B containing the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine.

EXAMPLE 3 preparation of a pharmaceutical formulation containing Lithospermum erythrorhizon oil, Oenothera biennis oil, Oxyphenylsalicylic acid

Grinding 3g of phenelzine into fine powder of 100 meshes, adding the fine powder into mixed oil of the lithospermum oil and the evening primrose oil, and uniformly mixing, wherein the mixed oil comprises 10g of the lithospermum oil and 10g of the evening primrose oil. Heating 76.99g of vaseline to 60 +/-2 ℃, adding the uniformly mixed mixture of the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine, uniformly mixing, adding 0.01g of 6-di-tert-butyl-4-methylphenol while stirring, uniformly mixing, and cooling to room temperature to obtain the ointment A containing the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine.

EXAMPLE 4 preparation of a pharmaceutical formulation containing Lithospermum erythrorhizon oil, Oenothera biennis oil, and Oxyphenylsalicylic acid

Grinding 1g of the phenelzine into fine powder of 100 meshes, adding the fine powder into mixed oil of the lithospermum oil and the evening primrose oil, and uniformly mixing, wherein the mixed oil comprises 1g of the lithospermum oil and 1g of the evening primrose oil. Heating 96.99g of vaseline to 60 +/-2 ℃, adding the uniformly mixed mixture of the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine, uniformly mixing, adding 0.01g of 6-di-tert-butyl-4-methylphenol while stirring, uniformly mixing, and cooling to room temperature to obtain the ointment B containing the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine.

EXAMPLE 5 preparation of a pharmaceutical formulation containing Lithospermum erythrorhizon oil, Oenothera biennis oil, and Oxyphenylsalicylic acid

Grinding 10g of phenelzine into fine powder of 100 meshes, and adding the fine powder into mixed oil of the lithospermum oil and the evening primrose oil to be uniformly mixed, wherein the mixed oil comprises 40g of the lithospermum oil and 10g of the evening primrose oil. Heating vaseline 39.99g to 60 +/-2 ℃, adding the uniformly mixed mixture of the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine, uniformly mixing, adding 0.01g of 6-di-tert-butyl-4-methylphenol while stirring, uniformly mixing, and cooling to room temperature to obtain the ointment C containing the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine.

EXAMPLE 6 preparation of a pharmaceutical formulation containing Lithospermum erythrorhizon oil, Oenothera biennis oil, and Oxyphenylsalicylic acid

Grinding 10g of phenelzine into fine powder of 100 meshes, adding the fine powder into mixed oil of the lithospermum oil and the evening primrose oil, and uniformly mixing, wherein the mixed oil comprises 10g of the lithospermum oil and 30g of the evening primrose oil. Heating 49.99g of vaseline to 60 +/-2 ℃, adding the uniformly mixed mixture of the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine, uniformly mixing, adding 0.01g of 6-di-tert-butyl-4-methylphenol while stirring, uniformly mixing, and cooling to room temperature to obtain ointment D containing the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine.

Comparative example 1 preparation of salve containing Lithospermum oil alone

Heating 79.99g of vaseline to 60 +/-2 ℃, adding 20g of lithospermum oil, uniformly mixing, adding 0.01g of 6-di-tert-butyl-4-methylphenol while stirring, uniformly mixing, and cooling to room temperature to obtain an ointment E only containing lithospermum oil.

Experimental example 1 intervention experiment of varying contents of arnebia oil, evening primrose oil and ethoxybenzene salamide 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: statistical analysis using SPSS 16.0 software to measure data

And (3) representing that the change of observation indexes among different 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 lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine can effectively prevent the psoriasis induced by the imiquimod. As can be seen in FIG. 4, there was no redness on the surface using both group 1 and group 2 mice of the present invention, 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.

In addition, the cream containing 5% of lithospermum oil, 8% of evening primrose oil and 3% of ethoxybenzene willow amine has better prevention effect on the formation of an imiquimod-induced psoriasis mouse model than the cream containing 2.5% of lithospermum oil, 4% of evening primrose oil and 1.5% of ethoxybenzene willow amine.

Experimental example 2 study on therapeutic effect of salve A containing Lithospermum erythrorhizon oil, Oenothera biennis oil and Oxyphenylsalicylic amine on psoriasis mice

First, establishment of psoriasis model of mouse

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 modeling area of the group 2 mice was externally coated with 50mg of the salve a 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 results show that the salve A containing the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine has a treatment effect on psoriasis-like skin lesions, the 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 salve A containing Lithospermum erythrorhizon oil, Oenothera biennis oil, and Oxyphenylsalicylic acid amine on the intervention of the mouse model of Imquimod-induced psoriasis with salve E of the single ingredient (Lithospermum erythrorhizon oil) in 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 the ointment A obtained in example 3 in the modeling area; the modeled zone of group 2 mice was given topical 50mg of salve E, 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 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 change between day 1 and day 3 in group 1 and group 2 mice, and group 2 salve E had less intervention in skin lesion thickness than group 1 salve a from day 4. Intervention in the case of erythema of skin lesions: group 2 salve E was less effective in intervening erythema than salve a of group 1. Intervention in the case of scaling of skin lesions: there was no significant difference in lesion scaling intervention between day 1 and day 2 in group 1 and group 2 mice, and group 2 salve E had less intervention on lesion scaling than salve a in group 1 from day 3. 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 arnebia oil in the components of salve E was 2 times that of salve a, mice in group 1 that intervened with salve a had lighter erythema, less scaling, and better intervention on psoriasis-like lesions than mice in group 2 that intervened with salve E. Therefore, the ointment A containing the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine has better anti-inflammatory and anti-proliferation 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 lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine has a certain intervention effect on the psoriasis modeling process of mice, which indicates that the external preparation has the potential of clinically preventing the psoriasis; the results of the experimental example 2 show that the external preparation containing the lithospermum oil, the evening primrose oil and the ethoxybenzene willow amine has the treatment effect on psoriasis-like skin lesions, the action 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 prepared by combining the arnebia root oil, the evening primrose oil and the ethoxybenzene willow amine has better effect than the pharmaceutical preparation prepared by singly using the arnebia root oil. 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, psoriasis and the like.

The experiment shows that the effective dose of the arnebia oil in the skin external preparation for single administration is 10-100 mug; the recommended dose is 50-100 μ g/time and 1-3 times/day. The effective dose of the evening primrose oil in the preparation for single administration is 10-200 mug; the recommended dose is 50-100 μ g/time and 1-3 times/day. The effective dose of the ethoferoxil in the preparation for single administration is 10-100 mu g; the recommended dose is 10-100 μ g/time and the dosage is 1-3 times/day.

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.

Claims

1. A pharmaceutical preparation is characterized in that the effective components of the preparation comprise lithospermum oil, 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, purified 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: 0.01-90% of lithospermum oil; evening primrose oil 0.01-90%; 0.01-30% of ethoxybenzene willow amine and 0.01-99% of common auxiliary materials of medicinal preparations.

4. The pharmaceutical formulation of claim 3, wherein the formulation is in a dosage form comprising a salve, a cream, an ointment, a gel, a lotion, a liniment or a film.

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

step one, preparation of oil phase

step two, preparation of water phase

6. The pharmaceutical preparation according to claim 5, wherein the preparation comprises the following components in percentage by mass: 1-30% of lithospermum oil, 1-30% of evening primrose oil, 3% of cetearyl glucoside, 2% of glyceryl stearate, 3% of octadecanol, 6% of liquid paraffin, 0.01% of 6-di-tert-butyl-4-methylphenol, 1-10% of ethoxybenzene willow amine, 0.1% of methyl paraben, 0.1% of ethylparaben, 0.05% of disodium EDTA, 10% of glycerol, 0.05% of sodium metabisulfite and 40-72.69% of purified water.

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

8. The pharmaceutical preparation according to claim 7, wherein the preparation comprises the following components in percentage by mass: 1-30% of lithospermum oil, 1-30% of evening primrose oil, 1-10% of ethoxybenzene willow amine, 30-96.99% 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 or psoriasis.