阅读说明：本技术 一种克立硼罗外用制剂其制备方法及用途 (Cliboroluo external preparation and preparation method and application thereof ) 是由 刘小斌 翟洪 胡俊 于 2020-05-25 设计创作，主要内容包括：本发明涉及克立硼罗一种新的给药途径,更具体地说,涉及克立硼罗外用制剂、其制备方法及在制备治疗皮肤病的药物中的用途,属于医药技术领域。(The invention relates to a new administration route of Cliborol, in particular to a Cliborol external preparation, a preparation method thereof and application thereof in preparing a medicament for treating skin diseases, belonging to the technical field of medicines.)

1. A Cliborol external preparation is characterized by comprising a Cliborol single external preparation and a Cliborol transdermal absorption external preparation.

2. The krebs preparation for external use according to claim 1, wherein the drug in the krebs preparation for external use is krebs; the medicine of the external Cliborol preparation comprises Cliborol and related auxiliary materials.

3. The krusel external preparation according to claim 2, wherein the krusel accounts for 0.1-10% of the krusel in the krusel external preparation by mass; the weight percentage of the krebs in the medicine of the krebs external preparation is 0.1-10%, and the weight percentage of the related auxiliary materials in the krebs external preparation is 0.2-55%.

4. The external Cliborol preparation as claimed in claim 1, wherein the dosage form of the external Cliborol preparation comprises conventional external preparations and novel transdermal preparation dosage forms, wherein the conventional external preparation dosage forms comprise cream, gel, spray and coating agent; the novel transdermal preparation comprises solid lipid nanoparticles and a Cliborol solid lipid nanoparticle gel.

5. A method for preparing the solid lipid nanoparticles of crohnos according to claim 5, which is carried out by a high-pressure homogenization method according to the following steps:

(1) preparing an oil phase: weighing the medicine, the solid lipid material and the surfactant, heating to 55-85 ℃, and uniformly stirring to form an oil phase;

(2) preparing a water phase: dissolving a surfactant in an aqueous matrix component to form a water phase, and heating to 55-85 ℃;

(3) adding the water phase into the oil phase, preparing into primary emulsion by using a high-shear emulsifying machine, homogenizing for a plurality of times by using a high-pressure homogenizer, cooling to room temperature to form the solid lipid nanoparticles of the kresoxim-methyl, and sealing and storing at room temperature.

6. The method for preparing solid lipid nanoparticles of kresoxim according to claim 6, wherein the lipid nanoparticles of kresoxim are prepared from the raw materials,

the solid lipid material is selected from: partially esterified glycerides, triacylglycerides, steroids, fatty acids and waxes, or a combination thereof in any proportion;

the surfactant is selected from: any one or a combination of a plurality of phospholipids, poloxamer, brij, polysorbate, sodium glycerocholate and tyloxapol in any proportion;

the aqueous matrix component is selected from: any one of water or glycerin or two combinations in any proportion;

the formula of the single-component solid lipid nanoparticle is as follows:

kribolo: 0.1-10 parts by weight, solid lipid material: 0.5-30 parts by weight of an aqueous matrix component: 5-99.4 parts by weight, surfactant: 0.1-20 parts by weight;

the formula of the compound solid lipid nanoparticle is as follows:

kribolo: 0.1-10 parts by weight of related auxiliary materials: 0.2-35 parts by weight, solid lipid material: 0.5-30 parts by weight of an aqueous matrix component: 5-99.4 parts by weight, surfactant: 0.1-20 parts by weight.

7. A method for preparing the solid lipid nanoparticles of Cribolol according to claim 5, which is characterized in that the method comprises the following steps of:

(1) preparing an oil phase: dissolving the medicine, the solid lipid material and the surfactant in an organic solvent to form an oil phase;

(2) preparing a water phase: dissolving a surfactant in an aqueous base component to form an aqueous phase;

(3) heating the water phase to 55-85 ℃, slowly injecting the oil phase into the water phase under stirring, and stirring at constant temperature until the organic solvent is completely evaporated to form primary emulsion;

(4) and (3) rapidly dispersing the primary emulsion in another water phase at 0-2 ℃, and stirring in an ice bath to obtain the Clibolol solid lipid nanoparticles.

8. The method for preparing solid lipid nanoparticles of kresoxim according to claim 8,

the solid lipid material is selected from: any one or combination of a plurality of triacylglycerol esters, partially esterified glyceride esters, fatty acids, steroids and waxes in any proportion;

the organic solvent is selected from any one of acetone, ethanol and dichloromethane or a combination of several kinds of solvents in any proportion;

the surfactant is selected from: any one or a combination of a plurality of phospholipids, poloxamer, brij, polysorbate, sodium glycerocholate and tyloxapol in any proportion;

the aqueous matrix component is selected from any one of water or glycerol or two combinations in any proportion;

the formula of the single-component solid lipid nanoparticle is as follows:

kribolo: 0.1-10 parts by weight, solid lipid material: 0.5-30 parts by weight, organic solvent: 1-40 parts by mass of an aqueous matrix component: 5-99.4 parts by weight, surfactant: 0.2-30 parts by weight;

the formula of the compound solid lipid nanoparticle is as follows:

kribolo: 0.1-10 parts by weight of related auxiliary materials: 0.2-35 parts by weight, solid lipid material: 0.5-30 parts by weight, organic solvent: 1-40 parts by mass of an aqueous matrix component: 5-99.4 parts by weight, surfactant: 0.2 to 30 parts by weight.

9. Use of a krebs preparation for external use according to any one of claims 1 to 5 in the manufacture of a medicament for the treatment of a skin disorder.

Technical Field

The invention relates to a new administration route of Cliborol, in particular to a Cliborol external preparation, a preparation method thereof and application thereof in preparing a medicament for treating skin diseases, belonging to the technical field of medicines.

Background

Crisabiole (Crisabiole) is a phosphodiesterase-4 (PDE 4) inhibitor. PDE4 is a key regulator of inflammatory cytokine production in Atopic Dermatitis (AD), acting primarily through degradation of cyclic adenosine monophosphate. PDE4 activity is increased in circulating inflammatory cells in AD patients, and in vitro studies have shown that proinflammatory cytokine release is reduced following inhibition of PDE4 in monocytes.

The Cleprednol is a boron-containing small-molecule anti-inflammatory drug, and the action mechanism is not completely clarified. Both the critical phase III studies of kreb reached primary and secondary endpoints at 7 months 2015. The first line of long-term safety research results of kreb used for 10 months in 2015 show that kreb used intermittently for more than 12 months has good tolerance and safety.

Allergic dermatitis is a common recurrent chronic inflammatory skin disease, and patients usually present with chronic rashes characterized by inflammation and pruritus, which are better developed at skin folds, and symptoms usually last for more than 14 days. It is estimated that about 2500 million people in the united states are afflicted with allergic dermatitis (eczema), with infants and children accounting for 8% -18%. A large population of mild to moderate atopic dermatitis lacks safe and effective topical treatments.

Disclosure of Invention

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

the invention provides a Cliboroluo external preparation, which comprises a Cliboroluo single external preparation and a Cliboroluo external preparation.

Wherein the medicament in the clironic external preparation is clironic; the medicine of the external Cliborol preparation comprises Cliborol and other related auxiliary materials.

Furthermore, other related auxiliary materials in the external preparation of the Cliborol are also provided.

Wherein the mass percentage of the krusel in the krusel external preparation is 0.1-10%; the weight percentage of the krebs in the medicine of the krebs external preparation is 0.1-10%, and the weight percentage of the related auxiliary materials in the medicine of the krebs external preparation is 0.2-35%.

Further, the dosage form of the external preparation of the clavulanate includes the traditional external preparation and a novel transdermal preparation.

Wherein, the traditional external preparation dosage forms comprise cream, ointment, gel, spray and film coating agent; the novel transdermal preparation comprises solid lipid nanoparticles and a Cliborol solid lipid nanoparticle gel.

The cream of the invention is a uniform semisolid preparation formed by dissolving or dispersing a drug in an emulsion matrix.

The invention also provides a method for preparing the Cribolol cream, which comprises the following steps:

(1) preparing an oil phase: weighing the oily matrix component, placing on a water bath, heating to 50-100 ℃ for melting, stirring uniformly, and keeping the temperature;

(2) preparing a water phase: weighing surfactant and transdermal enhancer, dissolving in water-based matrix, heating to 50-100 deg.C, stirring, and keeping the temperature;

(3) slowly adding the oil phase into the water phase, and stirring for 10-90 minutes;

(4) opening cooling water, cooling to 45-60 ℃, adding the medicine, and continuing stirring;

(5) cooling to room temperature to obtain cream, stirring, packaging, and packaging.

Wherein the oily matrix component is selected from any one or combination of several of vaseline, paraffin, liquid paraffin, silicone oil, beeswax, stearic acid, lanolin and glyceryl monostearate;

the aqueous matrix component is selected from any one or a combination of several of glycerol, propylene glycol, ethanol and water in any proportion;

the surfactant is selected from one or more of glyceryl monostearate, triethanolamine, sodium dodecyl sulfate, polysorbate, sorbitan fatty acid, poloxamer, lecithin and gelatin in any proportion;

the transdermal enhancer is selected from any one or combination of several of laurocapram, polyethylene glycol and menthol in any proportion.

The formula of the single cream is as follows:

kribolo: 0.1-10 parts by weight of oily matrix component: 15-80 parts by weight of an aqueous matrix component: 20-85 parts by weight, surfactant: 0.5-20 parts by weight, transdermal enhancer: 0-20 parts by weight;

the formula of the compound cream is as follows:

kribolo: 0.1-10 parts by weight of related auxiliary materials: 0.2-35 parts by weight, oily matrix component: 15-80 parts by weight of an aqueous matrix component: 20-85 parts by weight, surfactant: 0.5-20 parts by weight, transdermal enhancer: 0 to 20 parts by weight.

The ointment is a uniform semisolid external preparation prepared by mixing a medicament and an oleaginous or water-soluble matrix.

The invention provides a method for preparing a Cliboron external preparation, which comprises the following steps:

(1) weighing the oily matrix component, placing on a water bath, heating to 50-100 ℃ for melting, stirring uniformly, and keeping the temperature;

(2) adding the medicine and skin penetration enhancer into the oily matrix, stirring, and cooling to room temperature.

Wherein the oily matrix component is selected from any one of vaseline, paraffin, liquid paraffin, silicone oil, beeswax, stearic acid, and lanolin or combination thereof at any ratio;

the transdermal enhancer is selected from any one or combination of several of laurocapram, polyethylene glycol and menthol in any proportion.

Further, the formulation of the single ointment is as follows:

kribolo: 0.1-10 parts by weight of oily matrix component: 45-100 parts by weight of a transdermal enhancer: 0-20 parts by weight;

the formula of the compound ointment is as follows:

kribolo: 0.1-10 parts by weight of related auxiliary materials: 0.2-35 parts by weight, oily matrix component: 45-100 parts by weight of a transdermal enhancer: 0 to 20 parts by weight.

The gel agent is a thick liquid or semisolid preparation with gel property, which is prepared from medicines and auxiliary materials.

The invention provides a method for preparing a Cliboroluo gel, which comprises the following steps:

(1) wetting and soaking the gel matrix component with a solvent for 24 hours to fully swell the gel matrix component; adding triethanolamine under stirring, and adjusting the pH value to 6.0-8.0 to form a transparent matrix for later use;

(2) dissolving the medicinal aqueous matrix component, adding into the gel matrix, and stirring;

(3) adding skin penetration enhancer, adding water-based matrix components to a sufficient amount, and stirring.

Wherein, the gel matrix component is selected from any one of carbomer, cellulose derivative, alginate, tragacanth, gelatin and starch or the combination of several kinds of carbomer, cellulose derivative, alginate, tragacanth, gelatin and starch in any proportion;

the aqueous matrix component is selected from any one or a combination of several of glycerol, propylene glycol, water and ethanol in any proportion;

the transdermal enhancer is selected from any one or combination of several of laurocapram, polyethylene glycol and menthol in any proportion.

Further, the formula of the single-component gel is as follows:

kribolo: 0.1-10 parts by weight of gel matrix component: 0.5-20 parts by weight of an aqueous matrix component: 35-100 parts by weight of triethanolamine: 0.3-3 parts by weight of transdermal enhancer: 0-20 parts by weight;

the formula of the compound gel is as follows:

kribolo: 0.1-10 parts by weight of related auxiliary materials: 0.2-35 parts by weight of gel matrix component: 0.5-20 parts by weight of an aqueous matrix component: 35-100 parts by weight of triethanolamine: 0.3-3 parts by weight of transdermal enhancer: 0 to 20 parts by weight.

The spray is a solution, emulsion or suspension of the medicine and proper auxiliary materials, is filled in a special device, and can be sprayed out in a mist shape when in use.

The invention provides a method for preparing a Kriboron spray, which comprises the following steps:

(1) weighing the medicinal aqueous matrix component, dissolving, and stirring;

(2) adding skin penetration enhancer, adding water-based matrix components to a sufficient amount, stirring, and packaging.

Wherein, the aqueous matrix component is selected from any one or a combination of several of glycerol, propylene glycol, water and ethanol in any proportion;

the transdermal enhancer is selected from any one or combination of several of laurocapram, polyethylene glycol and menthol in any proportion.

Further, the formula of the single-component gel is as follows:

kribolo: 0.1-10 parts by weight of an aqueous matrix component: 45-100 parts by weight of a transdermal enhancer: 0-20 parts by weight;

the formula of the compound gel is as follows:

kribolo: 0.1-10 parts by weight of related auxiliary materials: 0.2-35 parts by weight of an aqueous matrix component: 45-100 parts by weight of a transdermal enhancer: 0 to 20 parts by weight.

The film coating agent provided by the invention is an external liquid preparation which is formed into a film after the medicine is dissolved or dispersed in a solvent containing a film forming material and is applied to an affected part.

The invention provides a method for preparing a Clibolol coating agent, which comprises the following steps:

(1) adding the matrix component of the film coating agent into a proper amount of aqueous matrix component to enable the aqueous matrix component to naturally swell;

(2) weighing the medicinal aqueous matrix component, dissolving, and stirring;

(3) pouring into the coating agent matrix solution, and uniformly mixing;

(4) adding skin penetration enhancer, adding water-based matrix components to a sufficient amount, stirring, and packaging.

Wherein the coating agent matrix components are selected from: any one or a combination of several of polyvinyl alcohol, polyvinylpyrrolidone, chitosan, ethyl cellulose and polyvinyl formal acetaldehyde in any proportion;

the aqueous matrix component is selected from any one or a combination of several of glycerol, propylene glycol, water and ethanol in any proportion;

the transdermal enhancer is selected from any one or combination of several of laurocapram, polyethylene glycol and menthol in any proportion.

Further, the formulation of the single coating agent is as follows:

kribolo: 0.1-10 parts by weight of an aqueous matrix component: 25-99.5 parts by weight of transdermal enhancer: 0-20 parts by weight of coating agent matrix component: 0.5-20 parts by weight;

the formula of the compound film coating agent is as follows:

kribolo: 0.1-10 parts by weight of related auxiliary materials: 0.2-35 parts by weight of an aqueous matrix component: 25-99.5 parts by weight of transdermal enhancer: 0-20 parts by weight of coating agent matrix component: 0.5-20 parts by weight.

The solid lipid nanoparticle is a new generation solid submicron drug delivery system which is prepared by taking solid lipid as a carrier and wrapping or embedding a drug in a lipid core, has the particle size of 10-1000 nm, and has the advantages of good drug absorption, good stability, slow release, high safety and the like.

The invention provides a method for preparing a clironic solid lipid nanoparticle, which adopts a high-pressure homogenization method and comprises the following steps:

(1) preparing an oil phase: weighing the medicine, the solid lipid material and the surfactant, heating to 55-85 ℃, and uniformly stirring to form an oil phase;

(2) preparing a water phase: dissolving a surfactant in an aqueous matrix to form a water phase, and heating to 55-85 ℃;

(3) and adding the water phase into the oil phase, preparing a primary emulsion by using a high-shear emulsifying machine, homogenizing for 2-20 times by using a high-pressure homogenizer (the homogenization pressure ranges from 5000KPa to 150000KPa), cooling to room temperature to form the Clibolol solid lipid nanoparticles, and sealing and storing at room temperature.

Wherein the solid lipid material is selected from: triacylglycerol (such as tripalmitin and trilaurin), partially esterified glyceride (such as glyceryl monostearate), fatty acid (such as stearic acid and palmitic acid), steroid (such as cholesterol) and wax (such as paraffin and cetyl ester wax) or their mixture at any ratio;

the surfactant is selected from: any one or a combination of a plurality of phospholipids, poloxamer, brij, polysorbate, sodium glycerocholate and tyloxapol in any proportion;

the aqueous matrix component is selected from: either water or glycerol or a combination of the two in any proportion.

Further, the formula of the single-component solid lipid nanoparticle is as follows:

kribolo: 0.1-10 parts by weight, solid lipid material: 0.5-30 parts by weight of an aqueous matrix component: 5-99.4 parts by weight, surfactant: 0.1-20 parts by weight;

the formula of the compound solid lipid nanoparticle is as follows:

kribolo: 0.1-10 parts by weight of related auxiliary materials: 0.2-35 parts by weight, solid lipid material: 0.5-30 parts by weight of an aqueous matrix component: 5-99.4 parts by weight, surfactant: 0.1-20 parts by weight.

The invention also provides a method for preparing the solid lipid nanoparticles of the clironic bornurine, which adopts an emulsification evaporation-low temperature solidification method and comprises the following steps:

(1) preparing an oil phase: dissolving the medicine, the solid lipid material and the surfactant in an organic solvent to form an oil phase;

(2) preparing a water phase: dissolving a surfactant in an aqueous matrix to form an aqueous phase;

(3) heating the water phase to 55-85 ℃, slowly injecting the oil phase into the water phase at a stirring speed of 600-1200 r/min, and stirring at a constant temperature for 0.5-4 h until the organic solvent is completely evaporated to form primary emulsion;

(4) and (3) rapidly dispersing the primary emulsion in another water phase at 0-2 ℃, and stirring at 600-1200 r/min under ice bath to obtain the solid lipid nanoparticles of the kresoxim.

Wherein the solid lipid material is selected from: triacylglycerol (such as tripalmitin and trilaurin), partially esterified glyceride (such as glyceryl monostearate), fatty acid (such as stearic acid and palmitic acid), steroid (such as cholesterol) and wax (such as paraffin and cetyl ester wax) or their mixture at any ratio;

the organic solvent is selected from: any one or a combination of acetone, ethanol and dichloromethane in any proportion;

the surfactant is selected from: any one or a combination of a plurality of phospholipids, poloxamer, Brij, polysorbate, sodium glycerocholate and tyloxapol in any proportion;

the aqueous matrix component is selected from: either water or glycerol or a combination of the two in any proportion.

Further, the formula of the single-component solid lipid nanoparticle is as follows:

kribolo: 0.1-10 parts by weight, solid lipid material: 0.5-30 parts by weight, organic solvent: 1-40 parts by mass of an aqueous matrix component: 5-99.4 parts by weight, surfactant: 0.2-30 parts by weight;

the formula of the compound solid lipid nanoparticle is as follows:

kribolo: 0.1-10 parts by weight of related auxiliary materials: 0.2-35 parts by weight, solid lipid material: 0.5-30 parts by weight, organic solvent: 1-40 parts by mass of an aqueous matrix component: 5-99.4 parts by weight, surfactant: 0.2 to 30 parts by weight.

The solid lipid nanoparticle can be further combined with traditional forms such as gel and the like, and is convenient for skin administration.

The invention provides a method for preparing a Clibororo solid lipid nanoparticle gel, which comprises the following steps:

(1) adding the water-based matrix component into the gel matrix component to wet the gel matrix component, standing for 24h to fully swell the gel matrix component, adding triethanolamine while stirring, and adjusting the pH value to 6.5-7.5 to form a blank gel transparent matrix for later use;

(2) and adding the obtained clironic solid lipid nanoparticle dispersion liquid into the blank gel matrix, uniformly stirring, adding water matrix components to a sufficient amount, and uniformly stirring to obtain the clironic solid lipid nanoparticle gel.

Wherein, the gel matrix component is selected from any one of carbomer, cellulose derivative, alginate, tragacanth, gelatin and starch or the combination of several kinds of carbomer, cellulose derivative, alginate, tragacanth, gelatin and starch in any proportion;

the aqueous matrix component is selected from: any one of water or glycerin or two combinations in any proportion;

further, the formula of the solid lipid nanoparticle gel is as follows:

a krebs solid lipid nanoparticle dispersion liquid: 0.5-80.0 parts by weight of aqueous matrix component: 20-99.5 parts by weight of gel matrix component: 1.0-20 parts by weight, triethanolamine: 0.5-10.0 weight portions.

The invention also provides application of the external Cliborol preparation in preparing a medicament for treating skin diseases.

Wherein the skin diseases comprise immune skin diseases and inflammatory skin diseases.

Further, the immunological skin diseases include atopic dermatitis, eczema, dermatitis, lichen planus, psoriasis, vitiligo, rosacea and cutaneous sarcoidosis.

The invention provides a new administration route of the krebs, namely the krebs is prepared into an external preparation for treating dermatosis. According to the characteristic of the high fat-soluble medicine of the krebs, the krebs can be prepared into the traditional external preparation such as cream, ointment, gel, spray, film coating agent and the like. In order to further improve the water insolubility and skin absorption capacity of the Clarithrombos, the Clarithrombos can also be prepared into novel transdermal preparations such as solid lipid nanoparticles, solid lipid nanoparticle gels and the like. The novel transdermal preparations have small particle size, promote the medicine to rapidly permeate into the horny layer, simultaneously have good retention capacity of epidermis and dermis, can be used as a local treatment medicine carrier, improve the local absorption of the skin and relieve the systemic adverse reaction, have the characteristics of high safety, improve the local treatment effect of the skin and reduce the adverse reaction. The invention provides a new application of the external Cleprednol preparation in the treatment of skin diseases, expands the application range and clinical value of the Cleprednol and provides new clinical indications.

Detailed Description

The invention will be further described with reference to specific embodiments, and the advantages and features of the invention will become apparent as the description proceeds. These examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.

Example 1

Single cream formula:

the component names are respectively determined according to the dosage of 20 grams of Kelibuo, 40 grams of stearic acid, 40 grams of glyceryl monostearate, 40 grams of Vaseline, 20 grams of liquid paraffin, 70 grams of glycerol, 50 grams of triethanolamine, 3 grams of sodium dodecyl sulfate, 3 grams of laurocapram, 2 grams of purified water, and the total amount of 1000 grams

The preparation process comprises the following steps:

(1) oil phase: accurately weighing stearic acid, glyceryl monostearate, vaseline and liquid paraffin, heating in water bath to melt, stirring, and keeping the temperature at about 75 deg.C;

(2) water phase: accurately weighing glycerol, triethanolamine, laurocapram, sodium dodecyl sulfate and water, heating in water bath, stirring for dissolving, and heating to 75 deg.C.

The oil phase was slowly added to the water phase, stirred for 15 minutes, and then kept under stirring.

And opening cooling water, starting to cool to about 55 ℃, adding the formula amount of the Clibolol, and continuing stirring.

Cooling to room temperature to obtain cream, stirring, packaging, and packaging.

Example 2:

single cream formula:

the components are gram boron Rome 10g stearic acid 30g glycerin monostearate 60g Vaseline 20g liquid paraffin 30g glycerin 30g triethanolamine 5g purified water right amount total 1000g

The preparation process comprises the following steps:

(1) oil phase: accurately weighing stearic acid, glyceryl monostearate, vaseline and liquid paraffin, heating in water bath to melt, stirring, and keeping the temperature at about 75 deg.C;

(2) water phase: accurately weighing glycerol, triethanolamine, laurocapram and water, heating in water bath, stirring for dissolving, and heating to 75 deg.C.

The oil phase was slowly added to the water phase, stirred for 15 minutes, and then kept under stirring.

And opening cooling water, starting to cool to about 55 ℃, adding the formula amount of the Clibolol, and continuing stirring.

Cooling to room temperature to obtain cream, stirring, packaging, and packaging.

Example 3:

the compound cream formula comprises:

the amount of the components is 20g of Kelibuo, 100g of stearic acid, 120g of liquid paraffin, 20g of lanolin, 40g of glycerin, 40g of triethanolamine and 8ml of purified water, and the proper amount is 1000g

The preparation process comprises the following steps:

weighing stearic acid, liquid paraffin and lanolin, placing in the same container, heating to 80 deg.C, stirring, and using as oil phase; putting glycerol, triethanolamine and water into another container, heating to 80 deg.C, and stirring to obtain water phase; adding the oil phase into the water phase, stirring, adding the formula amount of Clibolol and triamcinolone acetonide when the temperature is reduced to 60 ℃, and stirring uniformly; cooling to room temperature, packaging, and packaging.

Example 4:

the compound cream formula comprises:

the components are 20g of Kelibuo, 100g of vaseline, 50g of octadecanol, 25g of liquid paraffin, 30g of glycerol, 30g of propylene glycol, 10g of ethanol, 10ml of sodium dodecyl sulfate, 10g of ethylparaben, 1g of purified water and 1000g of total amount

The preparation process comprises the following steps:

placing octadecanol, white vaseline and liquid paraffin in the same container, heating to 75 deg.C, stirring to obtain oil phase; putting glycerol, propylene glycol, sodium dodecyl sulfate and water into another container, heating to 75 deg.C, and stirring to obtain water phase; adding the oil phase into the water phase, stirring, adding the formula amount of the kresoxim and the halometasone and the ethanol solution of the ethylparaben when the temperature is reduced to 60 ℃, and uniformly stirring; cooling to room temperature, packaging, and packaging.

Example 5:

prescription of single ointment:

the components are 10g of keluo, 120g of lanolin, 100g of liquid paraffin, 630g of vaseline, a proper amount of laurocapram, 5g of total 1000g

The preparation process comprises the following steps:

heating lanolin, vaseline and liquid paraffin in water bath at 60 deg.C to melt, and stirring; adding the formula amount of the clironic bor and the laurocapram, and stirring uniformly; adding glycerol to reach a sufficient amount, and stirring. Cooling to room temperature, packaging, and packaging.

Example 6:

prescription of single-prescription gel:

the components are prepared from 20g of krebs, 10g of carbomer, 50g of propylene glycol, 50g of glycerol, 10g of triethanolamine, 10ml of ethanol, 20ml of laurocapram, 5g of purified water, and 1000g of total amount of purified water

The preparation process comprises the following steps:

adding glycerol and propylene glycol into carbomer 940 to moisten the carbomer, adding about 500ml distilled water, and standing for 24h to fully swell the carbomer; adding triethanolamine under stirring, and adjusting pH to 6.5-7.5 to form transparent matrix; dissolving Cliboroluo in ethanol, adding into the gel, and stirring; finally, azone and distilled water are added to reach the sufficient amount and stirred evenly, and the Cliboroluo gel is obtained.

Example 9:

prescription of single-prescription spray:

the component dosage of the composition is krebs 20g, ethanol 500ml, polysorbate 802g, water with proper amount and total amount of 1000g

The preparation process comprises the following steps:

weighing the aliskirol, adding the alisol to dissolve, adding the polysorbate 80 and water to a sufficient amount, stirring uniformly, and subpackaging to obtain the medicament.

Example 11:

prescription of single-prescription coating agent:

the components are Clibolol 20g, polyvinyl alcohol 12g, polyvinylpyrrolidone 10g, glycerol 50g, ethanol 500ml, water right amount 1000g

The preparation process comprises the following steps:

sprinkling polyvinyl alcohol and polyvinylpyrrolidone into a solution of glycerol and water with a proper amount to enable the polyvinyl alcohol and the polyvinylpyrrolidone to naturally swell; dissolving dl-Clonol in anhydrous ethanol, adding into the above solution, mixing, adding purified water to desired volume, and packaging.