阅读说明：本技术 一种环吡酮胺乳膏及其制备方法 (Ciclopirox olamine cream and preparation method thereof ) 是由 韦家华 刘玉 李丙寅 于 2021-06-30 设计创作，主要内容包括：本申请提供了一种环吡酮胺乳膏,其包含：12-18重量份的环丙酮胺；60-80重量份的十八醇；90-110重量份的凡士林；70-100重量份的液体石蜡；80-100重量份的硬脂酸；90-110重量份的保湿剂；1-2重量份的防腐剂；10-20重量份的透皮吸收剂；用纯化水补足至1500重量份；其中所述环吡酮胺乳膏在60℃±1℃、5℃±2℃或-15℃的条件下放置至少10天后,酸碱度为7.0±0.3。本申请的环吡酮胺乳膏对皮肤无刺激性,可以克服常规乳膏制剂有干燥感的缺点,用于皮肤时有利于角质层水合而产生润滑作用,并可以减少基质中水分的丢失；不酸败,对光、空气稳定。(The application provides ciclopirox olamine cream comprising: 12-18 parts by weight of cyclopropanolamine; 60-80 parts by weight of octadecanol; 90-110 parts by weight of vaseline; 70-100 parts by weight of liquid paraffin; 80-100 parts by weight of stearic acid; 90-110 parts by weight of a humectant; 1-2 parts by weight of a preservative; 10-20 parts by weight of a transdermal absorbent; adding purified water to 1500 parts by weight; wherein the pH value of the ciclopirox olamine cream is 7.0 +/-0.3 after the ciclopirox olamine cream is placed for at least 10 days at the temperature of 60 +/-1 ℃, 5 +/-2 ℃ or-15 ℃. The ciclopirox olamine cream has no irritation to the skin, can overcome the defect that the conventional cream preparation has dry feeling, is beneficial to the hydration of the horny layer to generate a lubricating effect when being applied to the skin, and can reduce the loss of water in a matrix; it has no rancidity and is stable to light and air.)

1. A ciclopirox olamine cream comprising:

12-18 parts by weight of cyclopropanolamine;

60-80 parts by weight of octadecanol;

90-110 parts by weight of vaseline;

70-100 parts by weight of liquid paraffin;

80-100 parts by weight of stearic acid;

90-110 parts by weight of a humectant;

1-2 parts by weight of a preservative;

10-20 parts by weight of a transdermal absorbent;

adding purified water to 1500 parts by weight;

wherein the pH value of the ciclopirox olamine cream is 7.0 +/-0.3 after the ciclopirox olamine cream is placed for at least 10 days at the temperature of 60 +/-1 ℃, 5 +/-2 ℃ or-15 ℃.

2. Ciclopirox olamine cream according to claim 1, the moisturizer being selected from propylene glycol (e.g. 1, 2-propylene glycol), glycerol, butylene glycol, hexylene glycol, xylitol, polyethylene glycol, polypropylene glycol, sorbitol, hyaluronic acid or any combination thereof. In some preferred embodiments, the humectant is 1, 2-propylene glycol.

3. Ciclopirox olamine cream according to claim 1, the preservative being selected from the group consisting of parabens (i.e. parabens), sorbic acid and its salts, benzoic acid and its salts, dehydroacetic acid and sodium salts, chlorocresol, thimerosal or any combination thereof; preferably, the preservative is a paraben.

4. Ciclopirox olamine cream according to claim 1, the transdermal absorbent is selected from lauryl alcohol sulfate, dodecyl methyl sulfoxide, oleyl alcohol, lauryl alcohol, dimethylformamide, 2-pyrrolidone, salicylic acid; preferably, the transdermal absorbent is sodium lauryl sulfate.

5. Ciclopirox olamine cream according to claim 1, comprising:

12-18 parts by weight of cyclopropanolamine;

60-80 parts by weight of octadecanol;

90-110 parts by weight of vaseline;

70-100 parts by weight of liquid paraffin;

80-100 parts by weight of stearic acid;

90-110 parts by weight of 1, 2-propanediol;

1-2 parts by weight of a preservative;

10-20 parts by weight of sodium lauryl sulfate;

make up to 1500 parts by weight with purified water.

6. Ciclopirox olamine cream according to claim 1, comprising:

15 parts by weight of cyclopropanolamine;

70-80 parts by weight of octadecanol;

95-105 parts by weight of vaseline;

70-80 parts by weight of liquid paraffin;

80-100 parts by weight of stearic acid;

95-105 parts by weight of 1, 2-propanediol;

1-2 parts by weight of a preservative;

12-18 parts by weight of sodium lauryl sulfate;

make up to 1500 parts by weight with purified water.

7. Ciclopirox olamine cream according to claim 1, comprising:

15 parts by weight of cyclopropanolamine;

80 parts by weight of octadecanol;

100 parts by weight of vaseline;

70 parts by weight of liquid paraffin;

80 parts by weight of stearic acid;

100 parts by weight of 1, 2-propanediol;

1.5 parts by weight of nipagin;

15 parts by weight of sodium lauryl sulfate;

make up to 1500 parts by weight with purified water.

8. A method of preparing ciclopirox olamine cream comprising:

(1) preparing an oil phase: mixing the formula amount of octadecanol, stearic acid, liquid paraffin, vaseline and preservative in a container, and heating to 80-90 ℃ to melt;

(2) preparing an aqueous phase: mixing 1/3-2/3 prescription amount of humectant, prescription amount of transdermal absorbent and prescription amount of purified water, and heating to 75-85 deg.C;

(3) emulsification: mixing the oil phase and the water phase at 75-85 deg.C, and cooling to 35-45 deg.C; add the prescribed amount of ciclopirox olamine and the remaining prescribed amount of propylene glycol.

9. The method according to claim 8, comprising:

(1) preparing an oil phase: mixing octadecanol, stearic acid, liquid paraffin, vaseline and nipagin in a formula amount in a container, and heating to 80-90 ℃ to melt;

(2) preparing an aqueous phase: mixing half of the prescription amount of propylene glycol, the prescription amount of sodium lauryl sulfate and the prescription amount of purified water, and heating to 80 ℃;

(3) emulsification: mixing the oil phase and the water phase at 80 deg.C, and cooling to 40 deg.C; add the prescribed amount of ciclopirox olamine and the remaining prescribed amount of propylene glycol.

10. Use of ciclopirox olamine cream according to any of the claims 1 to 7 for the preparation of antifungal medicaments.

Technical Field

The application relates to the field of ciclopirox olamine preparations, in particular to ciclopirox olamine cream and a preparation method thereof.

Background

Ciclopirox olamine is a broad-spectrum new-generation antifungal drug, and the fungi to be resisted comprise dermatophytes such as dermatophytes, microsporum, trichophyton and the like; yeasts such as Cryptococcus neoformans, Actinomycetes, Aspergillus, and absorption parasites; for a plurality of C⁺And C^-The bacterium, chlamydia and trichomonas can also kill a certain degree.

There is still a need in the art to develop ciclopirox olamine cream which is non-irritating to the skin, stable in nature, safe and effective.

Disclosure of Invention

The application provides ciclopirox olamine cream comprising:

12-18 parts by weight of cyclopropanolamine;

60-80 parts by weight of octadecanol;

90-110 parts by weight of vaseline;

70-100 parts by weight of liquid paraffin;

80-100 parts by weight of stearic acid;

90-110 parts by weight of a humectant;

1-2 parts by weight of a preservative;

10-20 parts by weight of a transdermal absorbent;

adding purified water to 1500 parts by weight;

wherein the pH value of the ciclopirox olamine cream is 7.0 +/-0.3 after the ciclopirox olamine cream is placed for at least 10 days at the temperature of 60 +/-1 ℃, 5 +/-2 ℃ or-15 ℃.

In some embodiments, the humectant is selected from propylene glycol (e.g., 1, 2-propylene glycol), glycerin, butylene glycol, hexylene glycol, xylitol, polyethylene glycol, polypropylene glycol, sorbitol, hyaluronic acid, or any combination thereof. In some preferred embodiments, the humectant is 1, 2-propylene glycol.

In some embodiments the preservative is selected from the group consisting of parabens (i.e., parabens), sorbic acid and its salts, benzoic acid and its salts, dehydroacetic acid and its sodium salts, chlorocresol, thimerosal, or any combination thereof; preferably, the preservative is a paraben.

In some embodiments, transdermal absorbents include, but are not limited to: lauryl alcohol sulfate, dodecyl methyl sulfoxide, oleyl alcohol, lauryl alcohol, dimethylformamide, 2-pyrrolidone and salicylic acid; preferably, the transdermal absorbent is sodium lauryl sulfate.

In some embodiments, the ciclopirox olamine cream comprises:

12-18 parts by weight of cyclopropanolamine;

60-80 parts by weight of octadecanol;

90-110 parts by weight of vaseline;

70-100 parts by weight of liquid paraffin;

80-100 parts by weight of stearic acid;

90-110 parts by weight of 1, 2-propanediol;

1-2 parts by weight of a preservative;

10-20 parts by weight of sodium lauryl sulfate;

adding purified water to 1500 parts by weight;

wherein the pH value of the ciclopirox olamine cream is 7.0 +/-0.3 after the ciclopirox olamine cream is placed for at least 10 days at the temperature of 60 +/-1 ℃, 5 +/-2 ℃ or-15 ℃.

In some embodiments, the ciclopirox olamine cream comprises:

15 parts by weight of cyclopropanolamine;

70-80 parts by weight of octadecanol;

95-105 parts by weight of vaseline;

70-80 parts by weight of liquid paraffin;

80-100 parts by weight of stearic acid;

95-105 parts by weight of 1, 2-propanediol;

1-2 parts by weight of a preservative;

12-18 parts by weight of sodium lauryl sulfate;

adding purified water to 1500 parts by weight;

wherein the pH value of the ciclopirox olamine cream is 7.0 +/-0.3 after the ciclopirox olamine cream is placed for at least 10 days at the temperature of 60 +/-1 ℃, 5 +/-2 ℃ or-15 ℃.

In some embodiments, the ciclopirox olamine cream comprises:

15 parts by weight of cyclopropanolamine;

80 parts by weight of octadecanol;

100 parts by weight of vaseline;

70 parts by weight of liquid paraffin;

80 parts by weight of stearic acid;

100 parts by weight of 1, 2-propanediol;

1.5 parts by weight of nipagin;

15 parts by weight of sodium lauryl sulfate;

adding purified water to 1500 parts by weight;

wherein the pH value of the ciclopirox olamine cream is 7.0 +/-0.3 after the ciclopirox olamine cream is placed for at least 10 days at the temperature of 60 +/-1 ℃, 5 +/-2 ℃ or-15 ℃.

In some embodiments, the ciclopirox olamine cream of the present application is a milky white cream, without rancidity, off-odor, discoloration, stiffening, oil-water separation, and flatulence.

The present application also provides a method of preparing ciclopirox olamine cream, comprising:

(1) preparing an oil phase: mixing the formula amount of octadecanol, stearic acid, liquid paraffin, vaseline and preservative in a container, and heating to 80-90 ℃ to melt;

(2) preparing an aqueous phase: mixing 1/3-2/3 prescription amount of humectant, prescription amount of transdermal absorbent and prescription amount of purified water, and heating to 75-85 deg.C;

(3) emulsification: mixing the oil phase and the water phase at 75-85 deg.C, and cooling to 35-45 deg.C; add the prescribed amount of ciclopirox olamine and the remaining prescribed amount of propylene glycol.

In some embodiments, the method comprises:

(1) preparing an oil phase: mixing octadecanol, stearic acid, liquid paraffin, vaseline and nipagin in a formula amount in a container, and heating to 80-90 ℃ to melt;

(2) preparing an aqueous phase: mixing half of the prescription amount of propylene glycol, the prescription amount of sodium lauryl sulfate and the prescription amount of purified water, and heating to 80 ℃;

(3) emulsification: mixing the oil phase and the water phase at 80 deg.C, and cooling to 40 deg.C; add the prescribed amount of ciclopirox olamine and the remaining prescribed amount of propylene glycol.

The application also provides the application of the ciclopirox olamine cream in preparing antifungal drugs.

The beneficial effect of this application is: the ciclopirox olamine cream has no irritation to the skin, can overcome the defect that the conventional cream preparation has dry feeling, is beneficial to the hydration of the horny layer to generate lubrication when being applied to the skin, and can reduce the loss of water in the matrix; it has no rancidity and is stable to light and air.

Detailed Description

In order to make the objects, technical solutions and advantages of the present application more apparent, the technical solutions of the present application will be clearly and completely described below through specific embodiments.

In the following examples, those not indicated with specific conditions were performed according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.

EXAMPLE 1 preparation of ciclopirox olamine cream

Recipes 1-4 shown in Table 1 were synthesized according to the following procedures.

TABLE 1 ciclopirox olamine cream

Mixing octadecanol, stearic acid, liquid paraffin, vaseline and nipagin in the formula amount, placing the mixture in a container, heating the mixture to 80-90 ℃ on a water bath to melt and mix the mixture uniformly, sieving the mixture, moving the mixture to a dosing barrel with an interlayer, and preserving the heat; heating the water phase (half of the formula amount of propylene glycol, sodium lauryl sulfate, and water) to 80 deg.C, slowly adding the oil phase into the water phase under stirring, stirring for emulsification, and cooling to 40 deg.C for use. Sieving ciclopirox olamine with a 100-mesh sieve and the formula amount and propylene glycol with a half formula amount to be ground into transparent state, adding the transparent substrate, continuously stirring to be in a thin cream state, then transferring the thin cream state into a dosing barrel, uniformly stirring, carrying out content measurement, filling, packaging, and warehousing after the full inspection is qualified.

Example 2 stability study of ciclopirox olamine cream

The samples of the four design formulas of example 1 were centrifuged at 3000r/min for 30min and placed at 55 ℃ for 6h for preliminary stability investigation tests, resulting in a layering of formula 1, a thinner formula 2, a moderately thinner formula 3 and a satisfactory formula 4. The irritation test was conducted by applying the samples of formulas 2, 3, and 4 to the skin, and as a result, formula 2 had a dry feel and formulas 3 and 4 felt well.

The prescriptions 3 and 4 are subjected to influence factor investigation test at 60 ℃ to determine the optimal prescription composition. Sealing the finished product in an aluminum tube, placing in a constant-temperature drying oven, sampling after 0, 5 and 10 days at the temperature of 60 +/-1 ℃, and determining according to stability investigation items. Table 2 shows the results of the investigation of recipes 3, 4.

TABLE 2 accelerated stability test results for recipes 3, 4

The results show that the quality indexes of the prescription 4 meeting the requirements are all within the specified range, and for the continuous investigation, the cream is placed at the low temperature of 5 +/-2 ℃ and the low temperature of-l 5 ℃ and sampled at different times, and the quality investigation results of the cream are shown in Table 3.

TABLE 3 investigation results of prescription samples

For further investigation, the sample of formula 4 was sealed in a glass tube, left for 10 days under an illumination of 4500lx ± 500lx, and sampled for the focus investigation items at 5 and 10 days, and the results are shown in table 4.

TABLE 4 light stability examination results of prescription 4

As a result, the stability of the above formulation was greatly affected by light irradiation, and it was found that the formulation was suitable for storage in the dark.

The above description is only a preferred embodiment of the present application and is not intended to limit the present application, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.