CN118845610A - A kind of mometasone furoate cream and preparation method thereof - Google Patents

Abstract

The invention relates to a cream containing mometasone furoate and a preparation method thereof, and in particular relates to a cream containing the following components in percentage by mass: 0.1% of mometasone furoate, 10% -20% of hexanediol, 1.0% -2.0% of hydrogenated soybean phosphatidylcholine, 0.5% -2.0% of titanium dioxide, 8% -15% of aluminum octenyl succinate starch, 4% -6% of white beeswax, 60% -70% of white vaseline and 2% -5% of acidified water, wherein the pH value of the acidified water is regulated by using a 10% phosphoric acid aqueous solution, and the viscosity of the white vaseline is less than or equal to 150000 mPa.S. The mometasone furoate emulsifiable paste disclosed by the invention has the advantages of low impurity content, stable product, good release characteristic, easiness in coating and dispersion and good use feeling.

Description

A kind of mometasone furoate cream and preparation method thereof

Technical Field

The invention relates to the field of pharmaceutical preparations, and in particular to an ointment containing mometasone furoate and a preparation method thereof.

Background Art

Mometasone furoate is a synthetic glucocorticoid drug with strong efficacy and low suppression of adrenal cortex function. Mometasone furoate cream has the effect of reducing inflammation and itching, and is very suitable for skin diseases that are responsive to glucocorticoids. However, mometasone furoate has extremely poor solubility in water and in commonly used solvents for topical medication, such as propylene glycol and hexylene glycol, which brings certain difficulties to the preparation of topical cream preparations.

At present, different solvents and prescription compositions have been used to develop topical pharmaceutical compositions containing mometasone furoate. Schering first developed it in 1988 and marketed it in China under the trade name of "Elocon" (hereinafter referred to as the "commercial preparation"). However, the release rate of the commercial preparation is too fast, which is easy to cause greater irritation to the skin. Long-term use may also cause side effects such as inhibition of the HAP axis, Cushing's syndrome, and menstrual cycle disorders due to the cumulative absorption of glucocorticoids. In contrast, Merck's leading mometasone furoate cream marketed in Europe, such as the Belgian mometasone furoate cream (hereinafter referred to as the "imported preparation"), is called Elocon. Its release rate is slower than that of the commercial preparation (about 1/4 of the commercial preparation). While meeting the requirements of sustained and effective pharmacological effects, it has less irritation and cumulative side effects, which is more in line with clinical use requirements; however, the viscosity of the imported preparation is too high, and the skin feels sticky and rough, which is easy to cause discomfort, and it is not easy to spread and can easily cause problems such as uneven application.

A few studies in the prior art have attempted to solve the above problems by increasing the proportion of water, reducing the proportion of oily excipient matrix, or increasing the amount of surfactant. Although the existing studies have reduced the viscosity of the prepared mometasone furoate cream to a certain extent, they cannot take into account the release rate that meets clinical requirements. On the other hand, the mometasone furoate cream prepared by the existing studies has produced new technical problems, resulting in major defects in product quality. For example, increasing the proportion of water and reducing the proportion of oily excipients, the cream is prone to long-term dehydration and hardening, and is difficult to preserve. For example, the mometasone furoate in the existing studies is partially suspended in the cream, which may cause the drug to deteriorate due to precipitation of drug particles; in addition, there are some existing studies The creams produced contain a high level of impurities.

Therefore, there is still a need for a mometasone furoate cream and a preparation method thereof that can effectively solve the problem of too fast release of commercially available preparations and the problem of too high viscosity and difficulty in spreading of imported preparations, and that is stable, easy to store, and meets pharmaceutical quality standards.

Summary of the invention

The invention provides a mometasone furoate cream, which has good release characteristics that meet clinical needs, suitable viscosity, easy spreading and dispersion, good use experience, and the product has a small impurity content, stable properties and is easy to store.

Specifically, the mometasone furoate cream of the present invention comprises the following components according to the mass ratio: 0.1% mometasone furoate, 60% to 70% white vaseline, 10% to 20% hexylene glycol, 1% to 2% phospholipid derivatives, 0.5% to 2.0% sunscreen, 8% to 15% starch sugar ester derivatives, 4% to 6% solid waxes, and no more than 5% water, wherein the viscosity of the white vaseline is ≤150000 mPa·S. The inventor has found through repeated studies that the viscosity of the mometasone furoate cream can be effectively reduced by adding white vaseline of a specific viscosity in a certain prescription ratio, for example, the viscosity of the white vaseline is ≤150000 mPa·S, so that it is easy to spread evenly, the skin feels delicate and refreshing, and a satisfactory drug release rate can be achieved, which meets the needs of clinical use. At the same time, the mometasone furoate cream of the present invention only needs a small amount of water and does not need to add auxiliary materials such as preservatives and antioxidants, so that a cream product with stable quality and easy storage can be obtained.

The phospholipid derivatives of the present invention can be conventionally selected, such as soybean lecithin, egg yolk lecithin, hydrogenated soybean phosphatidylcholine, dipalmitoyl phosphatidylcholine, and distearoyl phosphatidylcholine.

The sunscreen agent of the present invention can be titanium dioxide, zinc oxide or mica powder, preferably titanium dioxide.

The starch sugar ester derivative of the present invention is preferably selected from aluminum starch octenylsuccinate, sodium starch octenylsuccinate, sodium starch octadecenylsuccinate, aluminum starch decenylsuccinate, aluminum starch dodecenylsuccinate, lauric acid starch ester, myristic acid starch ester, palmitic acid starch ester, and octanoic acid starch ester.

The solid waxes of the present invention can be Japan wax, carnauba wax, beeswax, shellac wax, rice wax, cork wax, ozokerite, montan wax, lanolin wax and the like.

The mometasone furoate cream provided in certain embodiments of the present invention comprises the following components in terms of mass ratio: 0.1% mometasone furoate, 10% to 15% hexylene glycol, 1.0% to 2.0% hydrogenated soybean phosphatidylcholine, 0.5% to 2.0% titanium dioxide, 8% to 15% aluminum octenylsuccinate starch, 4% to 6% white beeswax, 60% to 70% white vaseline, and 2% to 5% acidified water, wherein the pH of the acidified water is adjusted with a 10% phosphoric acid aqueous solution, and the viscosity of the white vaseline is ≤150000 mPa·S.

The cream of the present invention is a water-in-oil cream, and the mometasone furoate of the present invention is dissolved in the cream.

Furthermore, the cream of the present invention preferably comprises the following components in terms of mass ratio: 0.1% mometasone furoate, 12% hexylene glycol, 1.5% hydrogenated soybean phosphatidylcholine, 1.0% titanium dioxide, 10% aluminum starch octenylsuccinate, 5% white beeswax, 67.4% white vaseline, and 3% acidified water, wherein the acidified water is adjusted to a pH of 2.5±0.5 with a 10% phosphoric acid aqueous solution, and the viscosity of the white vaseline is ≤150000 mPa·S.

Furthermore, the viscosity of the white vaseline in the cream of the present invention is 80000 mPa·S to 132000 mPa·S; preferably, in certain specific embodiments of the present invention, the viscosity of the white vaseline is 80179 mPa·S, 92078 mPa·S, or 131980 mPa·S.

On the other hand, the present invention provides a method for preparing the mometasone furoate cream, comprising the following steps:

i) preparing the oil phase: melting and mixing the prescribed amount of white vaseline, white beeswax and hydrogenated soybean phosphatidylcholine;

ii) preparing the aqueous phase: mixing and dissolving the prescribed amounts of acidified water, hexylene glycol and mometasone furoate;

iii) total mixing: adding the water phase to the oil phase, and adding titanium dioxide and aluminum octenyl succinate starch to mix;

iv) emulsification: (a) emulsification with slow stirring combined with a first homogenizer, wherein the homogenization frequency of the first homogenizer is not less than 35 Hz; (b) emulsification with slow stirring combined with a second homogenizer; (c) stopping homogenization;

v) rapidly cooling, discharging and filling to obtain the mometasone furoate cream;

The viscosity of the white vaseline is 80,000 mPa·S to 132,000 mPa·S, and the homogenization frequency of the first homogenizer is greater than the homogenization frequency of the second homogenizer.

Further, the homogenization frequency of the first homogenizer is ≥36Hz, the homogenization frequency of the second homogenizer is ≤25Hz, and the slow stirring speed is ≤80rpm; preferably, in the preparation method of mometasone furoate cream of the present invention, the homogenization frequency of the first homogenizer is 38Hz-55Hz, the second homogenization frequency is 15Hz-25Hz, and the slow stirring speed is 30rpm-50rpm; in certain more preferred specific embodiments, the homogenization frequency of the first homogenizer of the present invention is 38Hz, 45Hz or 50Hz, and the homogenization frequency of the second homogenizer is 18Hz, and the slow stirring speed is 45rpm.

Furthermore, the rapid cooling is a temperature drop of 23°C or more within 30 minutes; in certain specific embodiments of the present invention, the rapid cooling is more preferably a temperature drop from 60-68°C to below 45°C within 30 minutes.

Furthermore, the operating temperature of step ii), step iii) and step iv) is above 60°C, preferably 60-68°C. The present invention keeps the operating temperature of step ii), step iii) and step iv) above 60°C, which can keep the mometasone furoate dissolved quickly and always in a stable dissolved state during the preparation process; when the operating temperature is less than 60°C, the mometasone furoate dissolves very slowly, and it takes a lot of time to completely dissolve it, and even a small amount of solid cannot be dissolved and continues to be suspended in the matrix in a solid state, which is not conducive to the mixed emulsification operation in the preparation process and the stability of the product; preferably, the operating temperature is kept at 60-68°C, which can not only ensure the stable dissolved state of mometasone furoate, but also avoid unnecessary degradation of mometasone furoate, avoid the generation of impurities, and effectively reduce the impurity content of the cream.

The mometasone furoate cream of the present invention has good release characteristics, can significantly avoid side effects such as skin irritation and HAP axis inhibition caused by rapid release, and also has the advantages of low viscosity, easy coating, and good skin feel when used. At the same time, the cream of the present invention has good stability, low impurity content, and is easy to store.

definition

The homogenization emulsification in the present invention adopts common homogenization equipment in the field. The conversion relationship between the homogenization frequency and the rotation speed is 1 Hz = 57.6 rpm. For example, 50 Hz corresponds to a rotation speed of 2880 rpm, 38 Hz corresponds to a rotation speed of 2189 rpm, and 18 Hz corresponds to a rotation speed of 1037 rpm.

In the present invention, the slow stirring refers to stirring with conventional stirring equipment. The stirring speed of conventional stirring equipment in the art is mostly up to 200 rpm, and the slow stirring speed commonly used in the art is between 20 rpm and 150 rpm.

In the present invention, the viscosity of white vaseline is measured using an MCR302 rheometer at a temperature of 25°C using a PP25 rotor and a shear rate of 0.2 1/s in accordance with "Chinese Pharmacopoeia 2020 Edition Part Four General Rules 0633 Method 3, (2) Cone-Plate Rotational Viscometer".

The phospholipid derivatives described in the present invention refer to complex lipids containing phosphoric acid, including but not limited to lecithin, cephalin, soybean lecithin, phosphatidylethanolamine, dipalmitoylphosphatidylserine, distearoylphosphatidylserine, dipalmitoylphosphatidylinositol, distearoylphosphatidylinositol, egg yolk lecithin, hydrogenated soybean phosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, etc.

The starch sugar ester derivatives described in the present invention refer to a type of surfactant with emulsifying and thickening properties formed by using starch as raw material, starch sugar or maltose obtained by biological enzymatic hydrolysis, and then esterified, including fatty acid starch sugar esters and alkenyl succinic acid starch sugar esters. Common fatty acid starch esters include but are not limited to starch esters of natural organic fatty acids such as caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, arachidic acid, and behenic acid; common alkenyl succinate starch esters include but are not limited to octenyl succinate aluminum starch, decenyl succinate aluminum starch, dodecenyl succinate aluminum starch, tetradecenyl succinate aluminum starch, hexadecenyl succinate aluminum starch, octadecenyl succinate aluminum starch, sodium octenyl succinate starch, sodium decenyl succinate starch, sodium dodecenyl succinate starch, sodium tetradecenyl succinate starch, sodium hexadecenyl succinate starch, sodium octadecenyl succinate starch, and the like.

The waxes described in the present invention refer to naturally produced or artificially synthesized oils such as animals, plants, kerosene shale, etc., which are combustible, easily fusible, insoluble in water, and mostly solid hydroxy alcohol fatty acid esters, including natural waxes and synthetic waxes. Common waxes include beeswax, spermaceti, insect wax, carnauba wax, wood wax, rice bran wax, sugarcane wax, candelilla wax, nutshell wax, lignite wax, mineral wax, crude paraffin, semi-refined paraffin, palm wax, soybean wax, polyethylene wax, Fischer-Tropsch wax, cattle wax, sheep wax, etc.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is a graph showing in vitro release curves of Examples 1 to 5, commercially available preparations, and imported preparations.

DETAILED DESCRIPTION

The present invention is further described below in conjunction with specific examples, but the following examples are only examples of the present invention and should not be used as limitations on the scope of the present invention. The raw materials and reagents used in the examples are all commercially available and do not limit the present invention.

The commercially available preparation used in the present invention has the trade name: Elocon, specification 0.1%, and is manufactured by Bayer Pharmaceuticals (Shanghai) Co., Ltd.; the imported preparation used in the present invention has the trade name: Elocon, specification 0.1%, and is manufactured by Merck Sharp & Dohme Limited (Belgium).

The cream prepared in the embodiment of the present invention was tested by methods known in the art, wherein the methods for viscosity, in vitro release rate, yield, and body sensation evaluation are as follows:

Viscosity test method: Use MCR302 rheometer, PP25 rotor at 25°C, shear rate of 0.21/s, and measure in accordance with "Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0633 Method 3, (2) Cone and Plate Rotational Viscometer".

In vitro release rate test method: Refer to the United States Pharmacopoeia General Chapter <1724> using the vertical diffusion cell method, ethanol aqueous solution as the release medium, and HPLC to complete the content determination.

The mean in vitro release rate refers to the average value of the in vitro release rate calculated by conducting 3 to 6 in vitro release rate tests on the same finished cream product.

Example 1

Preparation method:

1) Preparation of oil phase: melt white vaseline (viscosity 131980 mPa·S) and white beeswax at 70-75° C. according to the prescription ratio, stir and mix evenly, then add hydrogenated soybean phosphatidylcholine, continue stirring to obtain a uniformly dispersed mixed oil phase.

2) Preparation of acidified water: Adjust the pH of purified water to 2.5±0.5 with 10% phosphoric acid aqueous solution.

3) Preparation of aqueous phase: At 60-68° C., according to the prescription ratio, stir and mix hexylene glycol and acidified water evenly, then add mometasone furoate, and stir to completely dissolve the mometasone furoate.

4) Total mixing: at 60-68° C., add the water phase into the oil phase, then add titanium dioxide and aluminum octenyl succinate starch, and stir to mix.

5) Emulsification: a. Maintain the temperature at 60-68°C, and adopt slow stirring combined with homogenization emulsification for 30 minutes, wherein the slow stirring speed is 45 rpm and the homogenization frequency is 38 Hz;

b. Then use slow stirring combined with homogenization to emulsify for 30 minutes, wherein the slow stirring speed remains unchanged and the homogenization frequency is 18Hz;

c. Stop homogenizing.

6) Rapidly cool the emulsified system to below 45°C within 25-30 minutes, discharge the material, and fill it.

Example 2

White vaseline with a viscosity of 80179 mPa·S was used instead, and other conditions were the same as those in Example 1 to prepare an ointment.

Example 3

White vaseline with a viscosity of 92078 mPa·S was used instead, and other conditions were the same as those in Example 1 to prepare an ointment.

Example 4

The homogenizing frequency of operation a in step 5) in Example 1 was changed to 50 Hz, and the other conditions were the same as in Example 1 to prepare a cream.

Example 5

The homogenizing frequency of operation a in step 5) in Example 1 was changed to 45 Hz, and other conditions were the same as in Example 1 to prepare a cream.

Under the same conditions, the mean in vitro release rate, viscosity, content uniformity, and impurity content of Examples 1 to 5, as well as commercially available preparations and imported preparations were measured, and the results are shown in Table 1.

Table 1

“/” means not detected.

Through research, it is found that when the mean in vitro release rate is 0.8-1.2 μg/(cm ² *√h), it can basically meet the clinical use requirements; when the mean in vitro release rate is 0.95-1.05 μg/(cm ² *√h), it has a higher clinical advantage, while reducing irritation and reducing side effects, it better takes into account the balance of clinical effectiveness. For example, the mean in vitro release rate of imported preparations is 0.9886 μg/(cm ² *√h). The product obtained by the present invention has a mean in vitro release rate that meets the internal control quality standard, is consistent with the in vitro release rate of imported preparations, and has good release characteristics and clinical value; at the same time, the viscosity of the product obtained by the present invention is significantly improved compared with the imported preparation, which is about 1/2 of the imported preparation, is easy to spread evenly, has a refreshing and delicate skin feel, and basically has no or little greasy and sticky feeling. On the other hand, the product obtained by the present invention has good uniformity, the content of each sampling point meets the standard of 95%-105%, and the content uniformity range is less than 1.5%, the content of each sampling point fluctuates less, and the content is uniform and stable.

Example 6

The homogenizing frequencies of operations a and b in step 5) of Example 1 were changed to 35 Hz, and other conditions were the same as those of Example 1 to prepare a cream.

Example 7

The homogenizing frequency of operation b in step 5) of Example 1 was changed to 38 Hz, and the other conditions were the same as those of Example 1 to prepare a cream.

Example 8

The homogenizing frequency of operation a in step 5) of Example 1 was changed to 18 Hz, and the other conditions were the same as those of Example 1 to prepare a cream.

Example 9

The rapid cooling in step 6) of Example 1 was changed to slow cooling, and the temperature was lowered to 45° C. in about 2 hours. Other conditions were the same as those in Example 1, and a cream was prepared.

The same testing conditions as in Example 1 were used to test the in vitro release rate and viscosity of the creams obtained in Examples 6 to 9. The results are shown in Table 2.

Table 2

In the table, "/" indicates that no test was performed. Example 8 After the cream was prepared, a large amount of titanium dioxide was found to be deposited at the bottom of the tank, and the content uniformity was not tested.

According to Table 2, in the present invention, when a single frequency is used for homogenization, for example, when the homogenization frequency is 18 Hz, 35 Hz, and 38 Hz, the average in vitro release rate of the obtained product is improved to a certain extent compared with the commercially available preparations; the product viscosity is improved to a certain extent compared with the imported preparations.

Comparative Example 1-1

White vaseline with a viscosity of 169760 mPa·S was used instead, and other conditions were the same as those in Example 1 to prepare an ointment.

Comparative Example 1-2

White vaseline with a viscosity of 523150 mPa·S was used instead, and other conditions were the same as those in Example 1 to prepare an ointment.

Comparative Examples 1-3

White vaseline with a viscosity of 191850 mPa·S was used instead, and other conditions were the same as those in Example 1 to prepare an ointment.

Under the same testing conditions as Example 1, the in vitro release rate and viscosity of the creams obtained in Comparative Examples 1-1 to 1-3 were tested. The results are shown in Table 3.

Table 3

According to Table 3, when the viscosity of white vaseline in the present invention exceeds the range of 80000 to 132000 mPa·S, for example, when the viscosity of white vaseline is 169760 mPa·S, 523150 mPa·S, and 191850 mPa·S, respectively, the viscosity of the obtained product is improved to a certain extent compared with the imported preparation; however, the mean in vitro release rate of the obtained product does not meet the internal control release standard.

Comparative Example 2

Prepare the raw materials and reagents as follows:

1g mometasone furoate, 175g liquid paraffin, 265g white soft paraffin, 72g emulsified cetostearyl alcohol type A, 28g polyethylene glycol cetostearyl ether (each molecule has 20 to 30 units of ethylene oxide), 10g cetyl alcohol, 100g hexylene glycol, 10g glycerin, 1g xanthan gum, 338g purified water.

Prepare according to the following steps,

1) Add white soft paraffin, liquid paraffin, emulsified cetostearyl alcohol type A, polyethylene glycol cetostearyl ether and cetyl alcohol to a main container equipped with an anchor stirrer and a homogenizer. Heat these ingredients to 70°C and melt under stirring until a uniform mixture is obtained as the oil phase; 2) Pre-disperse xanthan gum in hexylene glycol as the xanthan gum phase; 3) Add 304g of purified water to the container and heat to 70°C. Add phosphoric acid to adjust the pH to 4 and dissolve under stirring. After homogenization, add the xanthan gum phase prepared in step 2; 4) Add the mixture prepared in step 3 to the oil phase under stirring and homogenize to obtain a uniform emulsion; 5) Cool the emulsion to 25°C under stirring; 6) Disperse mometasone furoate in glycerin, add the remaining 34g of purified water to dilute, add to the emulsion for homogenization, and obtain a cream. The in vitro release rate was tested under the same test conditions as in Example 1, and the average in vitro release rate was found to be 2.9999 μg/(cm2*√h), which did not meet the internal control quality standards.

Comparative Example 3

Prepare the raw materials and reagents as follows:

1g mometasone furoate, 0.27g phosphoric acid, 100g cetostearyl alcohol, 40g light liquid paraffin, 80g glycerol, 100g mono- and distearic acid glyceryl, 70g 95% ethanol, 2g titanium dioxide, 40g polysorbate 80, 0.5g ethylparaben, 566.23g purified water,

Follow the steps to prepare,

1) Place the prescribed amount of cetostearyl alcohol, light liquid paraffin, and mono- and distearic glyceryl in an oil phase container, heat to 85°C, stir to dissolve, and keep warm at 85°C for later use as the oil phase; 2) Place 539.5g of purified water, the prescribed amount of glycerol, and 20g of polysorbate 80 in a water phase container, heat to 85°C, stir evenly, and keep warm at 85°C for later use as the water phase; 3) Add the prescribed amount of phosphoric acid to the remaining 26.73g of purified water to prepare a 1.0% phosphoric acid solution for later use; 4) Preliminarily mix and disperse the prescribed amount of ethylparaben, mometasone furoate, and the remaining 20g of polysorbate 80, then add the prescribed amount of 95% ethanol, and stir at 400rpm until dissolved, as the main drug solution; 5 ) The aqueous phase was pumped into a vacuum emulsifier, titanium dioxide was added, stirred and dispersed uniformly, and kept warm at 85°C; the oil phase was then pumped in, the homogenizer was started (2000rpm, 10 minutes), and the emulsion matrix was prepared by slow stirring (80rpm, 10 minutes), and the temperature was cooled to 50°C-55°C by stirring; then a 1.0% phosphoric acid solution was pumped in, the homogenizer was started (2000rpm, 5 minutes), and the temperature was kept warm at 50°C-55°C; finally, the main drug solution was pumped in, stirred uniformly, the homogenizer was started (2000rpm, 5 minutes), and the temperature was kept warm at 80rpm (25 minutes), and the cream was obtained by stirring below 50°C. The in vitro release rate mean was measured under the same test conditions as in Example 1, and the in vitro release rate mean was 2.2303μg/(cm2*√h), which did not meet the internal control quality standard.

Comparative Example 4

Prepare the raw materials and reagents as follows:

1g mometasone furoate, 691g white vaseline, 50g mono- and distearic glyceryl, 50g Span 80, 21g Tween 80, 12g titanium dioxide, 5g anhydrous citric acid, 100g propylene glycol, 70g purified water,

Follow the steps to prepare,

1) Weigh white vaseline, mono- and distearic glyceryl, Span 80, and titanium dioxide according to the prescription amount, heat and melt at 68°C and stir and mix evenly to obtain an oil phase; 2) Weigh Tween 80 and anhydrous citric acid according to the prescription amount, mix evenly, add mometasone furoate, heat to 45°C and mix evenly; 3) Weigh propylene glycol and water according to the prescription amount, mix and heat to 68°C, add the mixture prepared in step 2 to the propylene glycol aqueous solution, stir and mix evenly at 65°C to obtain an aqueous phase; 4) Slowly add the aqueous phase to the oil phase, emulsify and homogenize, add the aqueous phase, continue to homogenize evenly, continue to stir and slowly cool with cooling water after the homogenization is completed. Obtain an emulsifiable paste. The in vitro release rate mean and impurity content were detected under the same detection conditions as Example 1. The impurity content was 2.09%, and the in vitro release rate mean was 1.6314μg/(cm2*√h), which did not meet the internal control quality standards.

Experimental Example 1

The 9 finished cream products obtained in Examples 1 to 6, Comparative Example 2, Comparative Example 3, and Comparative Example 4 were centrifuged at 5000 rpm for 10 min to investigate the centrifugal stability of the creams. Another 9 finished cream products were added to 5 mL open test tubes, which were placed in an open hot air oven at 45°C for 2 days to investigate the properties of the creams. The results are shown in Table 4.

Table 4

sample Centrifugal stability Cream appearance Example 1 Keep it as it is White cream, fine paste Example 2 Keep it as it is White cream, fine paste Example 3 Keep it as it is White cream, fine paste Example 4 Keep it as it is White cream, fine paste Example 5 Keep it as it is White cream, fine paste Example 6 Keep it as it is White cream, fine paste Example 7 Keep it as it is White cream, fine paste Comparative Example 2 Obvious stratification The paste is slightly rough and becomes hard due to slight water loss. Comparative Example 3 Keep it as it is The paste is slightly rough and becomes hard due to slight water loss. Comparative Example 4 Slight delamination The paste is slightly rough and becomes hard due to slight water loss.

.

Experimental Example 2

The cream obtained in Example 1 (filled in an aluminum medicinal ointment tube) was placed in an environment of 25°C ± 2°C, 65% ± 5% RH for a long-term stability experiment, and samples were taken for detection at 3 months and 6 months respectively; the cream obtained in Example 1 (filled in an aluminum medicinal ointment tube) was placed in an environment of 30°C ± 2°C, 60% ± 5% RH for an accelerated stability experiment, and samples were taken for detection at 1 month, 2 months, 3 months, and 6 months respectively, to investigate the storage stability of the mometasone furoate cream in Example 1, and the results are shown in Table 5.

Table 5

“/” means not detected.

Experimental Example 3

10 volunteers (5 men and 5 women) with healthy body and mind and healthy skin were selected as test subjects. Examples 1 to 9, commercial preparations, and imported preparations were evenly applied to the back of each subject's hand with fingers, and the spread of the cream was evaluated from three aspects: spreadability, skin fineness, and skin greasy viscosity. Among them, easy spread and uniform dispersion were scored 8 to 10 points, spreadability and dispersion were generally scored 4 to 7 points, and spread difficulty and poor dispersion were scored 0 to 3 points; delicate skin and no granularity were scored 8 to 10 points, slightly granular skin was scored 4 to 7 points, rough skin and strong granularity were scored 0 to 3 points; refreshing and suitable skin was scored 8 to 10 points, greasy skin was scored 4 to 7 points, and greasy and sticky skin was scored 0 to 3 points. The average score of the test subjects was recorded as the evaluation result. The evaluation results are shown in Table 6.

Table 6

project Spreading and dispersion Skin feel Skin feel greasy viscosity Example 1 9.1 9.8 9.0 Example 2 9.2 9.5 8.9 Example 3 9.5 9.2 9.1 Example 4 9.0 9.2 9.0 Example 5 9.1 9.0 9.2 Example 6 8.1 6.3 9.0 Example 7 7.9 7.5 8.9 Example 8 8.2 4.2 9.0 Example 9 8.0 7.0 8.8 Commercially available preparations 9.6 7.1 6.2 Imported preparations 1.5 8.5 2.3

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Claims (10)

1. A mometasone furoate emulsifiable paste which is characterized by comprising the following components in percentage by mass: 0.1% of mometasone furoate, 60% -70% of white vaseline, 10% -20% of hexanediol, 1% -2% of phospholipid derivative, 0.5% -2.0% of opacifier, 8% -15% of starch sugar ester derivative, 4% -6% of wax and no more than 5% of water, wherein the viscosity of the white vaseline is less than or equal to 150000 mPa.S.

2. The cream of claim 1, wherein the phospholipid derivative is selected from the group consisting of soy lecithin, egg yolk lecithin, hydrogenated soy phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, the opacifier is selected from the group consisting of titanium dioxide, zinc oxide, mica powder, and the starch sugar ester derivative is selected from the group consisting of aluminum octenyl succinate starch, sodium starch octenyl succinate, sodium starch octadecenyl succinate, aluminum decenyl succinate starch, aluminum dodecenyl succinate starch, starch laurate, starch myristate, starch palmitate, starch caprylate, and the waxes are selected from the group consisting of japan wax, carnauba wax, beeswax, shellac wax, rice wax, cork tree wax, ozokerite, montan wax, lanolin wax.

3. The cream according to claim 1, characterized by comprising the following components in mass ratio: 0.1 percent of mometasone furoate, 60 to 70 percent of white vaseline, 10 to 20 percent of hexanediol, 1.0 to 2.0 percent of hydrogenated soybean phosphatidylcholine, 0.5 to 2.0 percent of titanium dioxide, 8 to 15 percent of aluminum octenyl succinate starch, 4 to 6 percent of white beeswax and 2 to 5 percent of acidified water, wherein the pH value of the acidified water is regulated by using a 10 percent phosphoric acid aqueous solution, and the viscosity of the white vaseline is less than or equal to 150000 mPa.S.

4. The cream of claim 1, wherein the cream is a water-in-oil cream, and the mometasone furoate is dissolved in the cream.

5. The cream according to any one of claims 1 to 4, characterized in that it comprises the following components in mass ratio: 0.1% mometasone furoate, 12% hexanediol, 1.5% hydrogenated soybean phosphatidylcholine, 1.0% titanium dioxide, 10% aluminum octenyl succinate starch, 5% white beeswax, 67.4% white vaseline and 3% acidified water, wherein the pH of the acidified water is adjusted to 2.5+/-0.5 by using a 10% phosphoric acid aqueous solution, and the viscosity of the white vaseline is less than or equal to 150000 mPa.S.

6. The cream of claim 5, wherein the white petrolatum has a viscosity of 80000 mPa-S to 132000 mPa-S.

7. A process for preparing mometasone furoate cream as claimed in any one of claims 1 to 6, comprising the steps of,

I) Preparing an oil phase: melting and mixing the prescription amount of white vaseline, white beeswax and hydrogenated soybean phosphatidylcholine;

ii) preparing an aqueous phase: mixing and dissolving the prescription amount of acidified water, hexanediol and mometasone furoate;

iii) Total mixing: adding the water phase into the oil phase, adding titanium dioxide and aluminum octenyl succinate starch, and mixing;

iv) emulsification: (a) emulsifying in combination with slow stirring and first homogenization; (b) emulsifying in combination with slow stirring and a second homogenization; (c) stopping homogenization;

v) rapidly cooling, discharging and filling to obtain the mometasone furoate emulsifiable paste;

Wherein the white vaseline has a viscosity of 80000 mPa.S to 132000 mPa.S, and the first homogenizing frequency is greater than the second homogenizing frequency.

8. The method of claim 7, wherein the first homogenizing frequency is greater than or equal to 36Hz, the second homogenizing frequency is greater than or equal to 25Hz, and the slow stirring speed is greater than or equal to 80rpm.

9. The method of claim 7, wherein the rapid cooling is by 23 ℃ or more within 30 minutes.

10. The process according to claim 7, wherein the operating temperature of step ii), step iii), step iv) is above 60 ℃, preferably 60-68 ℃.