Amorolfine hydrochloride cream and preparation method thereof
By adding modified liquid paraffin to amorolfine hydrochloride cream, the fungal structure is destroyed and its growth is inhibited, thus solving the problem of insufficient cream stability and achieving improved stability and antibacterial effects.
Patent Information
- Application Number
- CN202510979450.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-16
- Publication Date
- 2025-09-30
AI Technical Summary
The stability of the amorolfine hydrochloride cream in the prior art is insufficient, and it is difficult to effectively maintain its antibacterial effect.
Modified liquid paraffin is used to work synergistically with other ingredients in the amorolfine hydrochloride cream formula to inhibit fungal growth by destroying the fungal structure and function. At the same time, the addition of modified liquid paraffin improves the stability of the product.
The stability and antibacterial effect of amorolfine hydrochloride cream are improved, the uniform release of active ingredients is promoted, and the long-term effectiveness of the product under different environmental conditions is ensured.
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of pharmaceuticals, and particularly relates to an amorolfine hydrochloride cream and a preparation method thereof. Background Art
[0002] Amorolfine hydrochloride is a new broad-spectrum antifungal drug and a morpholine derivative. It inhibits and kills fungi by interfering with the biosynthesis of ergosterol in fungal cell membranes. Amorolfine hydrochloride has broad antimicrobial properties, demonstrating excellent antimicrobial efficacy against yeasts, dermatophytes, molds, dematiaceae, and dimorphic fungi.
[0003] Existing report about amorolfine hydrochloride cream in prior art.For example, Chinese patent CN 119235756 A discloses a kind of amorolfine hydrochloride cream and preparation method thereof, specifically: with amorolfine hydrochloride, white vaseline, liquid paraffin, carbomer 934P, polyoxyethylene 40 stearate, stearyl alcohol, phenoxyethanol, disodium edetate, sodium hydroxide and water as raw materials, prepare amorolfine hydrochloride cream in conjunction with specific equipment, simplify production process, be suitable for industrial scale production; For example Chinese patent CN 118477037 B discloses a kind of amorolfine hydrochloride cream, it is formed by material processing such as amorolfine hydrochloride, polyethylene glycol-7 stearate (Tefose 63), liquid paraffin, octadecanol and pseudomonas CGMCC1.15626 extract, improves the permeability of amorolfine hydrochloride cream.However, with regard to how to improve the stability of amorolfine hydrochloride, still need those skilled in the art to explore. Summary of the Invention
[0004] The present invention aims to provide an amorolfine hydrochloride cream and a preparation method thereof. The amorolfine hydrochloride has good stability.
[0005] The present invention provides an amorolfine hydrochloride cream, which comprises the following raw materials in percentage by mass: Amorolfine hydrochloride 0.27%-0.29%, octadecyl alcohol 4.74%-4.76%, white petrolatum 5.48%-5.50%, modified liquid paraffin 3.44%-3.46%, polyoxyl (40) stearate 2.84%-2.86%, phenoxyethanol 0.52%-0.54%, disodium edetate 0.08%-0.11%, carbomer homopolymer type B 0.70%-0.90%, sodium hydroxide 0.30%-0.50% and the balance water.
[0006] Preferably, the amorolfine hydrochloride cream comprises the following raw materials in percentage by mass: Amorolfine hydrochloride 0.28%, octadecyl alcohol 4.75%, white petrolatum 5.49%, modified liquid paraffin 3.45%, polyoxyl (40) stearate 2.85%, phenoxyethanol 0.53%, disodium edetate 0.10%, carbomer homopolymer type B 0.80%, sodium hydroxide 0.40% and the balance water.
[0007] Preferably, the preparation method of the modified liquid paraffin is as follows: Mixing liquid paraffin with boric acid to carry out chemical reaction to obtain primary liquid paraffin; The initially modified liquid paraffin is ultrasonically mixed with nano silicon nitride to obtain the modified liquid paraffin.
[0008] Preferably, the mass ratio of the liquid paraffin, boric acid and nano-silicon nitride is 100:10-15:6-8.
[0009] Preferably, the parameters of the chemical reaction include: temperature: 170-180°C, time: 40-50 min; The parameters of the ultrasonic mixing include: time of 40-50 minutes, temperature of 100-120° C., and frequency of 20,000-25,000 Hz.
[0010] The present invention provides a method for preparing the amorolfine hydrochloride cream described in the above technical solution, comprising the following steps: (1) Preparation of aqueous phase material: At 25-30° C., carbomer homopolymer type B is mixed with water to swell, and then disodium edetate and phenoxyethanol are sequentially added to dissolve the mixture to obtain a dissolved product; At 60-80° C., the dissolved substance is mixed evenly with polyoxyethylene (40) stearate to obtain an aqueous phase material; (2) Preparation of oil phase material: Mix and melt white vaseline, modified liquid paraffin and stearyl alcohol at 60-80°C to obtain an oil phase; (3) Homogenization and pH adjustment The aqueous phase material and the oil phase material are mixed and then sequentially subjected to a first homogenization stirring and a second homogenization stirring to obtain a homogenized sample; Mixing the homogenized sample with sodium hydroxide and stirring at high speed to obtain a mixture; (4) Mixing Amorolfine hydrochloride and the mixture are sequentially mixed, dispersed, and cooled to obtain amorolfine hydrochloride cream.
[0011] Preferably, the conditions for the first homogenizing stirring include: temperature of 70-80°C, time of 10-15 minutes, and speed of 14000-15000 rpm; The conditions for the second homogenizing stirring include: temperature of 60-65° C., time of 20-25 min, and speed of 14000-15000 rpm.
[0012] Preferably, the conditions for high-speed homogenous stirring include: temperature of 60-65° C., time of 5-10 min, and speed of 20,000-25,000 rpm.
[0013] Preferably, the mixing and dispersing conditions include: temperature of 55-60° C., time of 15-20 min, and speed of 10000-15000 rpm.
[0014] Preferably, the cooling temperature is 35-40°C.
[0015] Beneficial effects: The present invention provides an amorolfine hydrochloride cream, which comprises the following raw materials, measured in percentage by mass: 0.27%-0.29% amorolfine hydrochloride, 4.74%-4.76% octadecyl alcohol, 5.48%-5.50% white vaseline, 3.44%-3.46% modified liquid paraffin, 2.84%-2.86% polyoxyl (40) stearate, 0.52%-0.54% phenoxyethanol, 0.08%-0.11% disodium edetate, 0.70%-0.90% carbomer homopolymer type B, 0.30%-0.50% sodium hydroxide, and the balance water.
[0016] The present invention adds modified liquid paraffin to amorolfine hydrochloride cream. On the one hand, it can synergize with the active ingredients of amorolfine hydrochloride cream to destroy the structure and function of fungi and accelerate fungal cell death. On the other hand, amorolfine hydrochloride cream can inhibit the respiration of corresponding enzymes by locking water, blocking energy synthesis and inhibiting fungal growth. Therefore, the amorolfine hydrochloride cream provided by the present invention has strong stability and good antibacterial effect.
[0017] In addition, the present invention also provides a preparation method of amorolfine hydrochloride cream. By performing different treatments on different raw materials, it is not only beneficial to improve the stability of the product, but also to promote the uniform release of its active ingredients, providing a scientific basis for preventing and treating fungi. DETAILED DESCRIPTION
[0018] The sources of some materials of the present invention are shown in Table 1: Table 1 Sources of materials
[0019] The carbomer homopolymer type B of the present invention is preferably carbomer 974PNF.
[0020] In order to further illustrate the present invention, the solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be understood as limiting the scope of protection of the present invention.
[0021] Example 1 A preparation method of amorolfine hydrochloride cream comprises the following steps: 1. Preparation of modified liquid paraffin Liquid paraffin and boric acid were mixed in a mass ratio of 1000 g:150 g, and the mixture was reacted at 170° C. for 40 min to obtain primary modified liquid paraffin; 80 g of nano-silicon nitride was added to the modified liquid paraffin, and the mixture was ultrasonically reacted at 100° C. and 25,000 Hz for 40 min to obtain modified liquid paraffin; 2. The amorolfine hydrochloride cream comprises the following raw materials in percentage by mass: Amorolfine hydrochloride 0.28%, octadecyl alcohol 4.75%, white vaseline 5.49%, modified liquid paraffin 3.45%, polyoxyl (40) stearate 2.85%, phenoxyethanol 0.53%, disodium edetate 0.10%, carbomer homopolymer type B 0.80%, sodium hydroxide 0.40%, fermentation broth of composite bacteria 0.17% and the balance water, according to the above proportions, are weighed and set aside; 3. Preparation of Amorolfine Hydrochloride Cream (1) Preparation of aqueous phase Add the prescribed amount of purified water to the aqueous phase mixing tank, add carbomer homopolymer type B at room temperature (25-30°C), stir to allow carbomer homopolymer type B to fully absorb water and swell until completely dissolved, then add disodium edetate and phenoxyethanol in sequence, after complete dissolution, raise the temperature to 80°C, add the prescribed amount of polyoxyethylene stearate (40), stir to allow all to dissolve completely, and keep warm; (2) Oil phase preparation Add the weighed white vaseline, modified liquid paraffin, and octadecyl alcohol into the oil phase mixing tank, set the temperature to 80°C and heat until all are melted, and keep warm; (3) Homogenization The melted oil phase mixture was vacuum-sucked into the water phase tank, the temperature was set at 70°C, and the mixture was stirred at 15,000 rpm for 10 minutes to form colostrum; the colostrum was then cooled to 60°C and homogenized at 15,000 rpm for 20 minutes to obtain a homogenized sample; (4) pH adjustment The weighed sodium hydroxide was added to the homogenized sample, and the mixture was stirred and dissolved at 60°C and 25000 rpm for 5 minutes to adjust the pH to obtain a pH-adjusted sample. (5) Mixed Amorolfine hydrochloride was added to the pH-adjusted sample, stirred at 60°C and 15,000 rpm for 15 minutes, and then the temperature was lowered. The sample was placed in 40°C and 30°C water, stirred, and cooled. When the sample temperature was <30°C, amorolfine hydrochloride cream was obtained.
[0022] Comparative Example 1 A preparation method of amorolfine hydrochloride cream comprises the following steps: The only difference from Example 1 is that liquid paraffin is added to the amorolfine hydrochloride cream; In terms of mass percentage, the amorolfine hydrochloride cream comprises the following raw materials: Amorolfine hydrochloride 0.28%, octadecyl alcohol 4.75%, white vaseline 5.49%, liquid paraffin 3.45%, polyoxyl (40) stearate 2.85%, phenoxyethanol 0.53%, edetate disodium 0.10%, carbomer homopolymer type B 0.80%, sodium hydroxide 0.40% and the balance water are weighed according to the above proportions and set aside.
[0023] Comparative Example 2 A preparation method of amorolfine hydrochloride cream comprises the following steps: The only difference from Example 1 is that the method for preparing modified liquid paraffin in step 1 is as follows: 1. Preparation of modified liquid paraffin Liquid paraffin and boric acid were mixed in a mass ratio of 1000 g:150 g, and reacted at 170° C. for 40 min to obtain modified liquid paraffin.
[0024] Comparative Example 3 A preparation method of amorolfine hydrochloride cream comprises the following steps: The only difference from Example 1 is that the method for preparing modified liquid paraffin in step 1 is as follows: 1. Preparation of modified liquid paraffin Liquid paraffin and nano silicon nitride were mixed in a mass ratio of 1000 g:80 g, and ultrasonically reacted at 100° C. and 25000 Hz for 40 minutes to obtain modified liquid paraffin.
[0025] Comparative Example 4 A preparation method of amorolfine hydrochloride cream comprises the following steps: The only difference from Example 1 is that the method for preparing modified liquid paraffin in step 1 is as follows: 1. Preparation of modified liquid paraffin Liquid paraffin and boric acid were mixed in a mass ratio of 1000 g:200 g, and the mixture was reacted at 170° C. for 40 min to obtain primary modified liquid paraffin. 80 g of nano-silicon nitride was added to the modified liquid paraffin, and the mixture was ultrasonically reacted at 100° C. and 25,000 Hz for 40 min to obtain modified liquid paraffin.
[0026] Stability test of amorolfine hydrochloride cream after packaging The amorolfine hydrochloride cream prepared in Example 1 and Comparative Examples 1-4 was packaged in aluminum pharmaceutical ointment tubes. 30 tubes were randomly divided into three groups for each treatment and stored at 60°C (high temperature), 4°C (low temperature), and 25°C (normal temperature), respectively. The samples on day 0 and day 40 were tested. Three tubes were taken for each sample and the average value was taken. The results are shown in Tables 1 and 2.
[0027] Among them, the qualified standard of microbial limit requirements is: take the sample to be tested and check it according to the law (General Rules 1105 and 1106 of Part IV of the Chinese Pharmacopoeia 2020 Edition). The total number of aerobic bacteria in each 1mL of the test sample shall not exceed 10 2 The total number of cfu, mold and yeast should not exceed 10 1 cfu; Staphylococcus aureus and Pseudomonas aeruginosa shall not be detected.
[0028] Table 1 Effects of different treatments on the parameters of amorolfine hydrochloride cream (day 0)
[0029] Table 2 Effects of different treatments on the parameters of amorolfine hydrochloride cream (day 40)
[0030] Combining the data in Table 1 and Table 2, it can be seen that when the amorolfine hydrochloride cream is prepared using the technical solutions in Example 1 and Comparative Example 4, the product has good stability after being stored at low temperature and at a high temperature for 40 days.
[0031] Stability test of amorolfine hydrochloride cream after opening Three tubes of amorolfine hydrochloride cream packaged in aluminum pharmaceutical ointment tubes in Example 1 and Comparative Example 4 were taken and stored at room temperature (temperature 23-27°C, relative humidity 50%-60%). The packaging of the amorolfine hydrochloride cream was opened once in the morning and once in the evening. The properties, uniformity, and microbial limits of the amorolfine hydrochloride cream were tested on the 10th and 20th days after the start of the test. During the test, three tubes were taken for each treatment, and the initial acid amorolfine content was taken as 1. The percentage of the acid amorolfine content at different times was calculated. The results are shown in Table 3.
[0032] Table 3 Effects of different treatments on the parameters of amorolfine hydrochloride cream
[0033] As can be seen from the data in Table 3, when amorolfine hydrochloride cream is prepared using the technical solutions in Example 1 and Comparative Example 4, good stability is maintained even after the product is opened, and although the percentage of amorolfine acid content decreases, it still meets the requirements. It can be seen that the technical solution provided by the present invention is beneficial for improving the stability of the corresponding product and maintaining the retention of the active ingredient.
[0034] Accelerated testing Ten tubes of amorolfine hydrochloride cream packaged in aluminum pharmaceutical ointment tubes in Example 1 and Comparative Example 4 were placed in an environment of 40° C., 70% relative humidity, and 5000 Lx for storage. The stable preparation of amorolfine hydrochloride cream was tested on the 0th day, 3rd month, and 6th month of storage. During the test, 3 tubes were taken for each treatment. The results are shown in Table 4.
[0035] Table 4 Effects of different treatments on the indicators of amorolfine hydrochloride cream
[0036] Combined with the data in Table 4, it can be seen that compared with the technical solution in Comparative Example 4, when the amorolfine hydrochloride cream is prepared using the technical solution in Example 1, the corresponding product can still maintain good stability even when stored under high temperature, high humidity and high light conditions. In summary, the present invention is by adding modified liquid paraffin to amorolfine hydrochloride cream, on the one hand it can synergize with the active ingredient of amorolfine hydrochloride cream, destroy the structure and function of fungi, accelerate fungal cell death; on the other hand, amorolfine hydrochloride cream can inhibit the respiration of corresponding enzymes by locking water, blocking energy synthesis, and inhibiting fungal growth. After preparing amorolfine hydrochloride cream in conjunction with the preparation method provided by the present invention, amorolfine hydrochloride has good stability, is conducive to promoting the uniform release of its active ingredient, and provides a scientific basis for preventing and treating fungi.
[0037] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.
Claims
1. An amorolfine hydrochloride cream, characterized in that In terms of mass percentage, the amorolfine hydrochloride cream comprises the following raw materials: Amorolfine hydrochloride 0.27%-0.29%, octadecyl alcohol 4.74%-4.76%, white petrolatum 5.48%-5.50%, modified liquid paraffin 3.44%-3.46%, polyoxyl (40) stearate 2.84%-2.86%, phenoxyethanol 0.52%-0.54%, disodium edetate 0.08%-0.11%, carbomer homopolymer type B 0.70%-0.90%, sodium hydroxide 0.30%-0.50% and the balance water.
2. Amorolfine hydrochloride cream according to claim 1, characterized in that, In terms of mass percentage, the amorolfine hydrochloride cream comprises the following raw materials: Amorolfine hydrochloride 0.28%, octadecyl alcohol 4.75%, white petrolatum 5.49%, modified liquid paraffin 3.45%, polyoxyl (40) stearate 2.85%, phenoxyethanol 0.53%, disodium edetate 0.10%, carbomer homopolymer type B 0.80%, sodium hydroxide 0.40% and the balance water.
3. Amorolfine hydrochloride cream according to claim 1, characterized in that, The preparation method of the modified liquid paraffin is as follows: Mixing liquid paraffin with boric acid to carry out chemical reaction to obtain primary liquid paraffin; The initially modified liquid paraffin is ultrasonically mixed with nano silicon nitride to obtain the modified liquid paraffin.
4. Amorolfine hydrochloride cream according to claim 3, characterized in that, The mass ratio of the liquid paraffin, boric acid and nano-silicon nitride is 100:10-15:6-8.
5. Amorolfine hydrochloride cream according to claim 3, characterized in that, The parameters of the chemical reaction include: temperature: 170-180°C, time: 40-50min; The parameters of the ultrasonic mixing include: time of 40-50 minutes, temperature of 100-120° C., and frequency of 20,000-25,000 Hz.
6. The method for preparing the amorolfine hydrochloride cream according to any one of claims 1 to 5, characterized in that: The steps include: (1) Preparation of aqueous phase material: At 25-30° C., carbomer homopolymer type B is mixed with water to swell, and then disodium edetate and phenoxyethanol are sequentially added to dissolve the mixture to obtain a dissolved product; At 60-80° C., the dissolved substance is mixed evenly with polyoxyethylene (40) stearate to obtain an aqueous phase material; (2) Preparation of oil phase material: Mix and melt white vaseline, modified liquid paraffin and stearyl alcohol at 60-80°C to obtain an oil phase; (3) Homogenization and pH adjustment The aqueous phase material and the oil phase material are mixed and then sequentially subjected to a first homogenization stirring and a second homogenization stirring to obtain a homogenized sample; Mixing the homogenized sample with sodium hydroxide and stirring at high speed to obtain a mixture; (4) Mixing Amorolfine hydrochloride and the mixture are sequentially mixed, dispersed, and cooled to obtain amorolfine hydrochloride cream.
7. The preparation method according to claim 6, characterized in that The conditions for the first homogenizing stirring include: temperature of 70-80°C, time of 10-15 minutes, and speed of 14000-15000 rpm; The conditions for the second homogenizing stirring include: temperature of 60-65° C., time of 20-25 min, and speed of 14000-15000 rpm.
8. The preparation method according to claim 6, characterized in that The conditions for high-speed homogenous stirring include: temperature of 60-65° C., time of 5-10 min, and speed of 20,000-25,000 rpm.
9. The preparation method according to claim 6, characterized in that The mixing and dispersing conditions include: temperature of 55-60° C., time of 15-20 min, and speed of 10000-15000 rpm.
10. The preparation method according to claim 6, characterized in that The cooling temperature is 35-40°C.