Benzoyl peroxide gel and preparation method thereof

Abstract

The invention provides benzoyl peroxide gel and a preparation method thereof. The preparation method comprises the following steps: S1, preparing an active phase; s2, preparing a gel phase; s3, mixing half of the active phase with the gel phase, and performing constant-temperature water bath to obtain low-crosslinking-degree gel; s4, uniformly granulating the low-crosslinking-degree gel, mixing the low-crosslinking-degree gel with the balance of the active phase, and performing vacuum negative-pressure stirring twice to obtain a material; and S5, adding a pH regulator into the material, regulating the pH value, discharging and filling. Nanocrystals are formed through benzoyl peroxide pretreatment, the surface area and activity are improved, the curative effect is enhanced on the premise of safety, uniform dispersion can be achieved, the stability of benzoyl peroxide in gel is improved, and the storage time is prolonged. A part of the active phase and the gel phase are mixed to form low-crosslinking-degree gel, the low-crosslinking-degree gel is uniformly granulated and then mixed with the remaining active phase, and the benzoyl peroxide gel is prepared through vacuum negative pressure, so that the swelling property can be improved, the stability and the permeability can be improved, and adverse reactions such as irritation to skin can be avoided.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a benzoyl peroxide gel and a preparation method thereof. Background Art

[0002] The original developer of benzoyl peroxide gel is Laboratoires Galderma. It was approved for marketing in France on March 19, 1986 under the trade name CUTACNYL, with specifications of 5% and 10%. In July of the same year, the 2.5% specification was launched. Currently, there is no single product on the market in the United States. Japan approved it for marketing in 2014, and China has an original imported variety. In December 2014, Japan approved the marketing of benzoyl peroxide gel from Maruho Co., Ltd., with specifications of 2.5%, 15g and 30g. This is the first time that benzoyl peroxide has been used in Japan to treat common acne, and it has bactericidal ability against Propionibacterium acnes.

[0003] Benzoyl peroxide has the advantages of broad-spectrum antifungal effect, resistance and anti-inflammatory effect, making it one of the ideal choices for treating fungal skin diseases. Benzoyl peroxide is a strong oxidant that can destroy the cell wall and cell membrane of fungi, causing the death of fungi, thereby playing a role in treating fungal infections. However, current benzoyl peroxide may produce irritation and dryness to the skin, causing symptoms such as skin redness, swelling and itching, and producing untoward reactions. In addition, if the benzoyl peroxide in the benzoyl peroxide gel is not evenly dispersed, the release rate cannot be accurately controlled, affecting activity, and the efficacy will also be affected, and the gel storage stability will also deteriorate simultaneously. Summary of the invention

[0004] In view of this, the present invention provides a benzoyl peroxide gel and a preparation method thereof to solve the above technical problems.

[0005] The technical solution of the present invention is achieved in this way:

[0006] A method for preparing benzoyl peroxide gel, the specific steps comprising:

[0007] S1. Preparation of active phase: Propylene glycol, poloxamer 182, edetate disodium and docusate sodium are added to purified water in sequence and stirred, then lauryl methacrylate / ethylene glycol dimethacrylate cross-linked polymer and colloidal silicon dioxide are added, stirring is continued, and benzoyl peroxide nanocrystals are added and stirred evenly to obtain an active phase;

[0008] The benzoyl peroxide nanocrystals are prepared by anti-solvent precipitation method assisted by ultrasonic treatment;

[0009] S2, gel phase preparation: add carbomer homopolymer type C and glycerol into purified water, stir evenly, and obtain a gel phase;

[0010] S3, taking half of the active phase and the gel phase and mixing them, and placing them in a constant temperature water bath to obtain a low cross-linking gel;

[0011] S4, uniformly granulating the low cross-linking degree gel, mixing it with the remaining active phase, and performing vacuum negative pressure stirring twice to obtain a material;

[0012] S5. Add a pH regulator to the material to adjust the pH to 5.1-5.4 to obtain benzoyl peroxide gel, discharge the material, and fill it.

[0013] Furthermore, in step S1, the preparation method of the benzoyl peroxide nanocrystals is specifically as follows:

[0014] (1) adding benzoyl peroxide to anhydrous ethanol at a solid-liquid ratio of 1:10-20 mg / mL, stirring and dissolving in a nitrogen atmosphere at 0-5° C. to obtain a benzoyl peroxide solution;

[0015] (2) adding the benzoyl peroxide solution dropwise into water at a speed of 5-15 mL / min, with a volume ratio of the benzoyl peroxide solution to water of 1:3-5, ultrasonically treating at 2000-3000 rpm for 10-20 min, aging for 2-4 days, filtering with a nanofiltration membrane, and freeze-drying to obtain benzoyl peroxide nanocrystals.

[0016] Further, in step S1, the active phase comprises the following raw materials in parts by weight: 5 parts of benzoyl peroxide nanocrystals, 3.8-4.2 parts of propylene glycol, 0.15-0.25 parts of poloxamer 182, 0.08-0.12 parts of edetate disodium, 0.04-0.06 parts of docusate sodium, 1.8-2.2 parts of lauryl methacrylate / ethylene glycol dimethacrylate crosslinked polymer, 0.020-0.022 parts of colloidal silicon dioxide, and 80-100 parts of purified water.

[0017] Furthermore, in step S1, the stirring speed is 400-600 rpm, the temperature is 25-28° C., and the time is 30-60 min; and the stirring time is continued for 30-40 min.

[0018] Furthermore, in step S2, the gel phase comprises the following raw materials in parts by weight: 0.7-0.9 parts of carbomer homopolymer type C, 3-5 parts of glycerol, and 40-60 parts of purified water.

[0019] Furthermore, in step S3, the temperature of the constant temperature water bath is 20-25° C., and the time is 10-14 hours.

[0020] Furthermore, in step S4, the sieves for uniform granulation are five sieves, specifically, the first sieve is 80 mesh, the second sieve is 100 mesh, the third sieve is 200 mesh, the fourth sieve is 300 mesh, and the fifth sieve is 500 mesh.

[0021] Furthermore, in step S4, the two vacuum negative pressures are specifically as follows: the first vacuum is set for 10-15 minutes, the vacuum degree is -0.06 to -0.08 MPa, and stirring is performed for 10-12 hours; the second vacuum is set for 25-30 minutes, the vacuum degree is -0.04 to -0.06 MPa, and stirring is performed for 13-15 hours.

[0022] A benzoyl peroxide gel is prepared by any of the above-mentioned preparation methods.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] 1. The present invention forms nanocrystals through benzoyl peroxide pretreatment, which not only increases the surface area and activity, enhances the therapeutic effect under the premise of safety, but also can be evenly dispersed, improves the stability of benzoyl peroxide in the gel, and prolongs the storage time.

[0025] 2. The present invention first mixes part of the active phase and the gel phase to form a low cross-linking degree gel, uniformly granulates, and then mixes with the remaining active phase under vacuum negative pressure to obtain a benzoyl peroxide gel, which can improve swelling, stability and permeability, and will not cause adverse reactions such as irritation to the skin. At the same time, the obtained benzoyl peroxide gel has a low impurity content and has good application value. DETAILED DESCRIPTION

[0026] In order to better understand the technical content of the present invention, specific embodiments are provided below to further illustrate the present invention.

[0027] Unless otherwise specified, the experimental methods used in the embodiments of the present invention are all conventional methods.

[0028] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can be obtained from commercial sources.

[0029] Example 1

[0030] The benzoyl peroxide gel of this embodiment includes an active phase and a gel phase, wherein the active phase includes the following raw materials in parts by weight: 5 parts of benzoyl peroxide nanocrystals, 4 parts of propylene glycol, 0.2 parts of poloxamer 182, 0.1 parts of edetate disodium, 0.05 parts of docusate sodium, 2 parts of lauryl methacrylate / ethylene glycol dimethacrylate cross-linked polymer, 0.021 parts of colloidal silicon dioxide, and 90 parts of purified water; the gel phase includes the following raw materials in parts by weight: 0.8 parts of carbomer homopolymer type C, 4 parts of glycerol, and 50 parts of purified water.

[0031] The preparation method of the above-mentioned benzoyl peroxide gel comprises the following specific steps:

[0032] S1. The preparation method of benzoyl peroxide nanocrystals is specifically as follows:

[0033] (1) adding benzoyl peroxide to anhydrous ethanol at a solid-liquid ratio of 1:15 mg / mL, stirring and dissolving under a nitrogen atmosphere at 3° C. to obtain a benzoyl peroxide solution;

[0034] (2) The benzoyl peroxide solution was added dropwise to water at a speed of 10 mL / min, with a volume ratio of the benzoyl peroxide solution to water of 1:4, and ultrasonically treated at 2500 rpm for 15 min, aged for 3 days, filtered with a nanofiltration membrane, and freeze-dried to obtain benzoyl peroxide nanocrystals.

[0035] S2. Preparation of active phase: Propylene glycol, poloxamer 182, edetate disodium and docusate sodium are added to purified water in sequence, and stirred at 500 rpm and 27° C. for 45 min, and then lauryl methacrylate / ethylene glycol dimethacrylate cross-linked polymer and colloidal silica are added, and stirring is continued for 35 min, and benzoyl peroxide nanocrystals are added and stirred evenly to obtain an active phase;

[0036] S3, gel phase preparation: add carbomer homopolymer type C and glycerol into purified water, stir evenly, and obtain a gel phase;

[0037] S4, take half of the active phase and mix with the gel phase, and place in a constant temperature water bath at 23°C for 12 hours to obtain a low cross-linking gel;

[0038] S5, the low cross-linking degree gel is uniformly granulated, specifically: the first sieve is 80 mesh, the second sieve is 100 mesh, the third sieve is 200 mesh, the fourth sieve is 300 mesh, and the fifth sieve is 500 mesh. After granulation, it is mixed with the remaining active phase and vacuum negative pressure stirring is performed twice, specifically: the first vacuuming is set to 13min, the vacuum degree is -0.06~-0.08MPa, and stirring is performed for 11h, and the second vacuuming is set to 28min, the vacuum degree is -0.04~-0.06MPa, and stirring is performed for 14h to obtain the material;

[0039] S6. Add a pH regulator to the material to adjust the pH to 5.1-5.4 to obtain benzoyl peroxide gel, discharge the material, and fill it.

[0040] Example 2

[0041] The benzoyl peroxide gel of this embodiment includes an active phase and a gel phase, wherein the active phase includes the following raw materials in parts by weight: 5 parts of benzoyl peroxide nanocrystals, 3.8 parts of propylene glycol, 0.15 parts of poloxamer 182, 0.08 parts of edetate disodium, 0.04 parts of docusate sodium, 1.8 parts of lauryl methacrylate / ethylene glycol dimethacrylate crosslinked polymer, 0.020 parts of colloidal silicon dioxide, and 80 parts of purified water; the gel phase includes the following raw materials in parts by weight: 0.7 parts of carbomer homopolymer type C, 3 parts of glycerol, and 40 parts of purified water.

[0042] The preparation method of the above-mentioned benzoyl peroxide gel comprises the following specific steps:

[0043] S1. The preparation method of benzoyl peroxide nanocrystals is specifically as follows:

[0044] (1) adding benzoyl peroxide to anhydrous ethanol at a solid-liquid ratio of 1:10 mg / mL, stirring and dissolving under a nitrogen atmosphere at 0° C. to obtain a benzoyl peroxide solution;

[0045] (2) The benzoyl peroxide solution was added dropwise to water at a rate of 5 mL / min, with a volume ratio of the benzoyl peroxide solution to water of 1:3, and ultrasonically treated at 2000 rpm for 10 min, aged for 2 days, filtered with a nanofiltration membrane, and freeze-dried to obtain benzoyl peroxide nanocrystals.

[0046] S2. Preparation of active phase: Propylene glycol, poloxamer 182, edetate disodium and docusate sodium are added to purified water in sequence, and stirred at 400 rpm and 25° C. for 30 min, and then lauryl methacrylate / ethylene glycol dimethacrylate cross-linked polymer and colloidal silica are added, and stirring is continued for 30 min, and benzoyl peroxide nanocrystals are added and stirred evenly to obtain an active phase;

[0047] S3, gel phase preparation: add carbomer homopolymer type C and glycerol into purified water, stir evenly, and obtain a gel phase;

[0048] S4, taking half of the active phase and the gel phase and mixing them, and placing them in a constant temperature water bath at 20°C for 10 hours to obtain a low cross-linking gel;

[0049] S5, the low cross-linking degree gel is uniformly granulated, specifically: the first sieve is 80 mesh, the second sieve is 100 mesh, the third sieve is 200 mesh, the fourth sieve is 300 mesh, and the fifth sieve is 500 mesh. After granulation, it is mixed with the remaining active phase and vacuum negative pressure stirring is performed twice, specifically: the first vacuuming is set to 10 minutes, the vacuum degree is -0.06 to -0.08 MPa, and stirring is performed for 10 hours. The second vacuuming is set to 25 minutes, the vacuum degree is -0.04 to -0.06 MPa, and stirring is performed for 13 hours to obtain the material;

[0050] S6. Add a pH regulator to the material to adjust the pH to 5.1-5.4 to obtain benzoyl peroxide gel, discharge the material, and fill it.

[0051] Example 3

[0052] The benzoyl peroxide gel of this embodiment includes an active phase and a gel phase, wherein the active phase includes the following raw materials in parts by weight: 5 parts of benzoyl peroxide nanocrystals, 4.2 parts of propylene glycol, 0.25 parts of poloxamer 182, 0.12 parts of edetate disodium, 0.06 parts of docusate sodium, 2.2 parts of lauryl methacrylate / ethylene glycol dimethacrylate crosslinked polymer, 0.022 parts of colloidal silicon dioxide, and 100 parts of purified water; the gel phase includes the following raw materials in parts by weight: 0.9 parts of carbomer homopolymer type C, 5 parts of glycerol, and 60 parts of purified water.

[0053] The preparation method of the above-mentioned benzoyl peroxide gel comprises the following specific steps:

[0054] S1. The preparation method of benzoyl peroxide nanocrystals is specifically as follows:

[0055] (1) adding benzoyl peroxide to anhydrous ethanol at a solid-liquid ratio of 1:20 mg / mL, stirring and dissolving at 5° C. in a nitrogen atmosphere to obtain a benzoyl peroxide solution;

[0056] (2) adding the benzoyl peroxide solution dropwise into water at a rate of 15 mL / min, with a volume ratio of the benzoyl peroxide solution to water of 1:5, ultrasonically treating at 3000 rpm for 20 min, aging for 4 days, filtering with a nanofiltration membrane, and freeze-drying to obtain benzoyl peroxide nanocrystals;

[0057] S2. Preparation of active phase: Propylene glycol, poloxamer 182, edetate disodium and docusate sodium are added to purified water in sequence, and stirred at 600 rpm and 28° C. for 60 min, and then lauryl methacrylate / ethylene glycol dimethacrylate cross-linked polymer and colloidal silica are added, and stirring is continued for 40 min, and benzoyl peroxide nanocrystals are added and stirred evenly to obtain an active phase;

[0058] S3, gel phase preparation: add carbomer homopolymer type C and glycerol into purified water, stir evenly, and obtain a gel phase;

[0059] S4, take half of the active phase and mix with the gel phase, and place in a constant temperature water bath at 25°C for 14 hours to obtain a low cross-linking gel;

[0060] S5, the low cross-linking degree gel is uniformly granulated, specifically: the first sieve is 80 mesh, the second sieve is 100 mesh, the third sieve is 200 mesh, the fourth sieve is 300 mesh, and the fifth sieve is 500 mesh. After granulation, it is mixed with the remaining active phase and vacuum negative pressure stirring is performed twice, specifically: the first setting is vacuuming for 15 minutes, the vacuum degree is -0.06 to -0.08 MPa, and stirring is performed for 12 hours. The second setting is vacuuming for 30 minutes, the vacuum degree is -0.04 to -0.06 MPa, and stirring is performed for 15 hours to obtain the material;

[0061] S6. Add a pH regulator to the material to adjust the pH to 5.1-5.4 to obtain benzoyl peroxide gel, discharge the material, and fill it.

[0062] Comparative Example 1

[0063] The difference from Example 1 is that benzoyl peroxide is not subjected to any treatment, and the other conditions are consistent with those of Example 1.

[0064] That is, the benzoyl peroxide gel of this comparative example comprises an active phase and a gel phase, wherein the active phase comprises the following raw materials in parts by weight: 5 parts of benzoyl peroxide, 4 parts of propylene glycol, 0.2 parts of poloxamer 182, 0.1 parts of edetate disodium, 0.05 parts of docusate sodium, 2 parts of lauryl methacrylate / ethylene glycol dimethacrylate crosslinked polymer, 0.021 parts of colloidal silicon dioxide, and 90 parts of purified water; the gel phase comprises the following raw materials in parts by weight: 0.8 parts of carbomer homopolymer type C, 4 parts of glycerol, and 50 parts of purified water.

[0065] The preparation method of the above-mentioned benzoyl peroxide gel comprises the following specific steps:

[0066] S1. Preparation of active phase: Propylene glycol, poloxamer 182, edetate disodium and docusate sodium are added to purified water in sequence, and stirred at 500 rpm and 27° C. for 45 min, and then lauryl methacrylate / ethylene glycol dimethacrylate cross-linked polymer and colloidal silica are added, and stirring is continued for 35 min. Benzoyl peroxide is added and stirred evenly to obtain an active phase;

[0067] S2, gel phase preparation: add carbomer homopolymer type C and glycerol into purified water, stir evenly, and obtain a gel phase;

[0068] S3, take half of the active phase and mix with the gel phase, and place in a constant temperature water bath at 23°C for 12 hours to obtain a low cross-linking gel;

[0069] S4, the low cross-linking degree gel is uniformly granulated, specifically: the first sieve is 80 mesh, the second sieve is 100 mesh, the third sieve is 200 mesh, the fourth sieve is 300 mesh, and the fifth sieve is 500 mesh. After granulation, it is mixed with the remaining active phase and vacuum negative pressure stirring is performed twice, specifically: the first vacuuming is set to 13min, the vacuum degree is -0.06~-0.08MPa, and stirring is performed for 11h, and the second vacuuming is set to 28min, the vacuum degree is -0.04~-0.06MPa, and stirring is performed for 14h to obtain the material;

[0070] S5. Add a pH regulator to the material to adjust the pH to 5.1-5.4 to obtain benzoyl peroxide gel, discharge the material, and fill it.

[0071] Comparative Example 2

[0072] The difference from Example 1 is that the active phase and the gel phase are directly mixed, and the rest is the same as Example 1.

[0073] That is, the preparation method of the benzoyl peroxide gel of this comparative example, the specific steps include:

[0074] S1. The preparation method of benzoyl peroxide nanocrystals is specifically as follows:

[0075] (1) adding benzoyl peroxide to anhydrous ethanol at a solid-liquid ratio of 1:15 mg / mL, stirring and dissolving under a nitrogen atmosphere at 3° C. to obtain a benzoyl peroxide solution;

[0076] (2) The benzoyl peroxide solution was added dropwise to water at a speed of 10 mL / min, with a volume ratio of the benzoyl peroxide solution to water of 1:4, and ultrasonically treated at 2500 rpm for 15 min, aged for 3 days, filtered with a nanofiltration membrane, and freeze-dried to obtain benzoyl peroxide nanocrystals.

[0077] S2. Preparation of active phase: Propylene glycol, poloxamer 182, edetate disodium and docusate sodium are added to purified water in sequence, and stirred at 500 rpm and 27° C. for 45 min, and then lauryl methacrylate / ethylene glycol dimethacrylate cross-linked polymer and colloidal silica are added, and stirring is continued for 35 min, and benzoyl peroxide nanocrystals are added and stirred evenly to obtain an active phase;

[0078] S3, gel phase preparation: add carbomer homopolymer type C and glycerol into purified water, stir evenly, and obtain a gel phase;

[0079] S4, the active phase and the gel phase are mixed, and vacuum negative pressure stirring is performed twice, specifically: the first vacuuming is set for 13 minutes, the vacuum degree is -0.06 to -0.08 MPa, and stirring is performed for 11 hours; the second vacuuming is set for 28 minutes, the vacuum degree is -0.04 to -0.06 MPa, and stirring is performed for 14 hours to obtain the material;

[0080] S5. Add a pH regulator to the material to adjust the pH to 5.1-5.4 to obtain benzoyl peroxide gel, discharge the material, and fill it.

[0081] Comparative Example 3

[0082] The difference from Example 1 is that uniform granulation is not performed in step S5, and the rest is the same as Example 1.

[0083] That is, the preparation method of the benzoyl peroxide gel of this comparative example, the specific steps include:

[0084] S1. The preparation method of benzoyl peroxide nanocrystals is specifically as follows:

[0085] (1) adding benzoyl peroxide to anhydrous ethanol at a solid-liquid ratio of 1:15 mg / mL, stirring and dissolving under a nitrogen atmosphere at 3° C. to obtain a benzoyl peroxide solution;

[0086] (2) The benzoyl peroxide solution was added dropwise to water at a speed of 10 mL / min, with a volume ratio of the benzoyl peroxide solution to water of 1:4, and ultrasonically treated at 2500 rpm for 15 min, aged for 3 days, filtered with a nanofiltration membrane, and freeze-dried to obtain benzoyl peroxide nanocrystals.

[0087] S2. Preparation of active phase: Propylene glycol, poloxamer 182, edetate disodium and docusate sodium are added to purified water in sequence, and stirred at 500 rpm and 27° C. for 45 min, and then lauryl methacrylate / ethylene glycol dimethacrylate cross-linked polymer and colloidal silica are added, and stirring is continued for 35 min, and benzoyl peroxide nanocrystals are added and stirred evenly to obtain an active phase;

[0088] S3, gel phase preparation: add carbomer homopolymer type C and glycerol into purified water, stir evenly, and obtain a gel phase;

[0089] S4, take half of the active phase and mix with the gel phase, and place in a constant temperature water bath at 23°C for 12 hours to obtain a low cross-linking gel;

[0090] S5, the low cross-linking gel and the remaining active phase are mixed, and vacuum negative pressure stirring is performed twice, specifically: the first vacuum is set for 13 minutes, the vacuum degree is -0.06 to -0.08 MPa, and stirring is performed for 11 hours; the second vacuum is set for 28 minutes, the vacuum degree is -0.04 to -0.06 MPa, and stirring is performed for 14 hours to obtain the material;

[0091] S6. Add a pH regulator to the material to adjust the pH to 5.1-5.4 to obtain benzoyl peroxide gel, discharge the material, and fill it.

[0092] Test Example 1

[0093] The benzoyl peroxide gels prepared in Examples 1-3 and Comparative Examples 1-3 were tested, and the test items and acceptance criteria are shown in Table 1.

[0094] Table 1

[0095]

[0096] The test results are shown in Table 2-3.

[0097] Table 2

[0098] sample Characteristics pH Viscosity / mPa·s content granularity Example 1 White uniform creamy gel 5.2 129300 101.4％ Comply with regulations Example 2 White uniform creamy gel 5.1 118700 100.2％ Comply with regulations Example 3 White uniform creamy gel 5.2 126600 102.1％ Comply with regulations Comparative Example 1 White uniform creamy gel 5.0 135800 99.8％ Comply with regulations Comparative Example 2 White uniform creamy gel 5.0 189900 101.1％ Comply with regulations Comparative Example 3 White uniform creamy gel 5.1 175800 102.2％ Comply with regulations

[0099] Table 3

[0100]

[0101] As can be seen from Tables 2-3, the various indicators of the benzoyl peroxide gel prepared in Examples 1-3 of the present invention are within the standards and the impurity content is low.

[0102] Test Example 2

[0103] The stability test of the benzoyl peroxide gel prepared in Examples 1-3 and Comparative Examples 1-3 was performed, specifically as follows: 1. Centrifugation: After centrifugation at 2500 r / min for 30 min, observe whether there is water precipitation and stratification; 2. Sample observation: The sample was placed in a transparent glass bottle and stored at room temperature and away from light for 6 months, and its sensory properties, pH and mildew were observed and measured once every 5 days. The results are shown in Table 4.

[0104] Table 4

[0105] sample pH changes Centrifugal observation Syneresis Save time Example 1 Slightly rising No stratification, no water precipitation none 12 months Example 2 Slightly rising No stratification, no water precipitation none 12 months Example 3 Slightly down No stratification, no water precipitation none 12 months Comparative Example 1 Significant increase Layering, water precipitation none 6 months Comparative Example 2 Significant increase Layering, water precipitation Syneresis 5 months Comparative Example 3 Significant increase Layering, water precipitation Syneresis 5 months

[0106] It can be seen from Table 4 that, relative to Comparative Examples 1-3, the benzoyl peroxide gel prepared in Examples 1-3 has excellent stability.

[0107] Test Example 3

[0108] 100 patients (18-38 years old, 50 men and 50 women) suffering from acne were selected and randomly divided into two groups. There were no significant differences in age, gender and acne degree between the two groups of patients. One group used the benzoyl peroxide gel of Example 1 of the present invention, and the other group used commercially available benzoyl peroxide gel (Bansay, manufactured by Galderma Pharmaceuticals, France). They washed their faces with warm water before applying the medicine each time, and smeared the medicine on the affected part after drying, once in the morning and evening, for a use period of 1 month, during which no other drugs or cosmetics were used.

[0109] Efficacy criteria: cured: acne subsided by more than 95%; markedly effective: acne subsided by 60%-94%; improved: acne subsided by 20%-59%; ineffective: acne subsided by less than 20%. Calculate the cure rate and total effective rate, total effective rate = (number of cured cases + number of markedly effective cases) / total number of cases, the results are shown in Table 5.

[0110] Table 5

[0111] sample Number of cases / person Cure rate Total Effectiveness Allergic symptoms (redness, swelling, itching) Example 1 50 84％ 94％ No allergy Commercially available group 50 40％ 76％ 6 people are allergic

[0112] It can be seen from Table 5 that, compared with the commercially available group, the benzoyl peroxide gel of Example 1 of the present invention has a good effect in treating acne, is non-irritating to the skin, and does not cause adverse symptoms such as allergies.

[0113] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing benzoyl peroxide gel, characterized in that: The specific steps include: S1. Preparation of active phase: Propylene glycol, poloxamer 182, edetate disodium and docusate sodium are added to purified water in sequence and stirred, then lauryl methacrylate / ethylene glycol dimethacrylate cross-linked polymer and colloidal silicon dioxide are added, stirring is continued, and benzoyl peroxide nanocrystals are added and stirred evenly to obtain an active phase; The benzoyl peroxide nanocrystals are prepared by anti-solvent precipitation method assisted by ultrasonic treatment; S2, gel phase preparation: add carbomer homopolymer type C and glycerol into purified water, stir evenly, and obtain a gel phase; S3, taking half of the active phase and the gel phase and mixing them, and placing them in a constant temperature water bath to obtain a low cross-linking gel; S4, uniformly granulating the low cross-linking degree gel, mixing it with the remaining active phase, and performing vacuum negative pressure stirring twice to obtain a material; S5. Add a pH regulator to the material to adjust the pH to 5.1-5.4 to obtain benzoyl peroxide gel, discharge the material, and fill it.

2. The method for preparing a benzoyl peroxide gel according to claim 1, wherein: In step S1, the preparation method of the benzoyl peroxide nanocrystals is specifically as follows: (1) adding benzoyl peroxide to anhydrous ethanol at a solid-liquid ratio of 1:10-20 mg / mL, stirring and dissolving in a nitrogen atmosphere at 0-5° C. to obtain a benzoyl peroxide solution; (2) adding the benzoyl peroxide solution dropwise into water at a speed of 5-15 mL / min, with a volume ratio of the benzoyl peroxide solution to water of 1:3-5, ultrasonically treating at 2000-3000 rpm for 10-20 min, aging for 2-4 days, filtering with a nanofiltration membrane, and freeze-drying to obtain benzoyl peroxide nanocrystals.

3. The method for preparing a benzoyl peroxide gel according to claim 1, wherein: In step S1, the active phase comprises the following raw materials in parts by weight: 5 parts of benzoyl peroxide nanocrystals, 3.8-4.2 parts of propylene glycol, 0.15-0.25 parts of poloxamer 182, 0.08-0.12 parts of edetate disodium, 0.04-0.06 parts of docusate sodium, 1.8-2.2 parts of lauryl methacrylate / ethylene glycol dimethacrylate crosslinked polymer, 0.020-0.022 parts of colloidal silicon dioxide, and 80-100 parts of purified water.

4. The method for preparing a benzoyl peroxide gel according to claim 1, wherein: In step S1, the stirring speed is 400-600 rpm, the temperature is 25-28° C., and the time is 30-60 min; the stirring time is 30-40 min.

5. The method for preparing a benzoyl peroxide gel according to claim 1, wherein: In step S2, the gel phase comprises the following raw materials in parts by weight: 0.7-0.9 parts of carbomer homopolymer type C, 3-5 parts of glycerol, and 40-60 parts of purified water.

6. The method for preparing a benzoyl peroxide gel according to claim 1, wherein: In step S3, the temperature of the constant temperature water bath is 20-25° C., and the time is 10-14 hours.

7. The method for preparing a benzoyl peroxide gel according to claim 1, characterized in that: In step S4, the sieves for uniform granulation are five sieves, specifically, the first sieve is 80 mesh, the second sieve is 100 mesh, the third sieve is 200 mesh, the fourth sieve is 300 mesh, and the fifth sieve is 500 mesh.

8. The method for preparing a benzoyl peroxide gel according to claim 1, wherein: In step S4, the two vacuum negative pressures are specifically as follows: the first vacuum is set for 10-15 minutes, the vacuum degree is -0.06 to -0.08 MPa, and stirring is performed for 10-12 hours; the second vacuum is set for 25-30 minutes, the vacuum degree is -0.04 to -0.06 MPa, and stirring is performed for 13-15 hours.

9. A benzoyl peroxide gel prepared by the preparation method according to any one of claims 1 to 8.

Images