Selenium disulfide lotion and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, in particular to a selenium disulfide lotion and a preparation method thereof. According to the invention, by introducing wet ball-milling ultra-micronized selenium disulfide, it is ensured that the D90 particle size of selenium disulfide is less than 5 [mu] m, the dispersibility and suspension stability of selenium disulfide in the lotion are significantly improved, sedimentation is effectively avoided, and the content uniformity is improved; high-speed shearing and high-pressure homogenization are combined, firstly, selenium disulfide is prepared into selenium disulfide slurry through high-speed shearing, and then agglomeration is further broken through high-pressure homogenization, so that selenium disulfide particles are uniformly dispersed in a system, and the layering phenomenon is effectively inhibited. According to the invention, a thickening system is optimized, and sodium carboxymethyl cellulose and carbomer are compounded for thickening, so that the lotion is endowed with more excellent thixotropy and stability while proper viscosity is ensured, and excessive flowing or excessive viscosity is avoided. The selenium disulfide lotion prepared by the invention is stable in character, uniform in content, not easy to layer and suitable and stable in viscosity.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, in particular to a selenium disulfide lotion and a preparation method thereof. Background Art

[0002] Selenium disulfide lotion is a commonly used topical dermatological drug, widely used to treat diseases such as dandruff, seborrheic dermatitis and tinea versicolor. The existing preparation process of selenium disulfide lotion usually has the following problems: Poor content uniformity: Selenium disulfide is an insoluble powder, which is prone to sedimentation during the preparation process, resulting in uneven content of the finished product, affecting the efficacy. Easy to stratify: After long-term storage, the lotion is prone to stratification, affecting the product appearance and user experience. Viscosity control is difficult and unstable: Too high viscosity will make pouring inconvenient, and too low viscosity will make it easy to flow, affecting the residence time of the drug in the affected area, and the viscosity will decrease after long-term storage. Insufficient control of raw material particle size: Too large raw material particle size will affect the dispersibility of the drug, and too small may cause agglomeration. Unstable properties: Some products may have problems such as color change or agglomeration. Summary of the Invention

[0003] In view of this, the object of the present invention is to provide a selenium disulfide lotion and a preparation method thereof. The selenium disulfide lotion prepared by the present invention has stable properties, uniform content, is not easy to delaminate, and has suitable and stable viscosity.

[0004] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0005] The present invention provides a method for preparing a selenium disulfide lotion, comprising the following steps:

[0006] Wet ball-milling selenium disulfide, the first water, and the dispersant to obtain a ball-milled slurry; wherein the D90 particle size of the selenium disulfide in the ball-milled slurry is less than 5 μm;

[0007] dissolving a matrix in the second water to obtain a matrix solution; the matrix comprising sodium carboxymethyl cellulose;

[0008] The ball-milled slurry, the first surfactant and the third water are subjected to high-speed shear homogenization treatment to obtain selenium disulfide slurry;

[0009] The selenium disulfide slurry and the matrix solution are mixed and then subjected to high-pressure homogenization to obtain a homogeneous slurry;

[0010] The carbomer pre-dispersion liquid is added to the homogeneous slurry, and then an inorganic base solution is added to adjust the pH value to 6-7, and water is added to the formula amount to obtain a selenium disulfide lotion.

[0011] Preferably, the shearing speed of the high-speed shear homogenization treatment is 4000-6000 rpm, and the shearing time is 5-15 minutes.

[0012] Preferably, the pressure of the high-pressure homogenization treatment is 60-100 MPa, and the number of times of the high-pressure homogenization treatment is 2-3 times.

[0013] Preferably, the dispersant includes polyvinyl alcohol; and the rotation speed of the wet ball mill is 2000-4000 rpm.

[0014] Preferably, the matrix further comprises a second surfactant and a humectant.

[0015] Preferably, the second surfactant includes one or more of sodium lauryl sulfate, sodium laureth sulfate, disodium laureth sulfosuccinate, ammonium lauryl sulfate, ammonium laureth sulfate and cocamidopropyl betaine; and the moisturizer includes one or more of glycerin, propylene glycol, butylene glycol, sodium hyaluronate and sorbitol.

[0016] Preferably, the selenium disulfide lotion comprises, by weight percentage, 1-3% selenium disulfide, 0.05-2% dispersant, 10.5-15.5% matrix, 0.5-1% first surfactant, 0.3-0.4% carbomer, an appropriate amount of inorganic base and the balance water; the content of sodium carboxymethyl cellulose in the selenium disulfide lotion is 0.4-0.6%.

[0017] Preferably, the first surfactant comprises Tween.

[0018] Preferably, the viscosity of the selenium disulfide lotion is 200-800 mPa·s.

[0019] The present invention provides a selenium disulfide lotion prepared by the preparation method described in the above scheme, wherein the D90 of the selenium disulfide lotion is less than 5 μm.

[0020] The invention provides a preparation method of a selenium disulfide lotion, comprising the following steps: wet ball-milling selenium disulfide, first water and a dispersant to obtain a ball-milled slurry; the D90 particle size of the selenium disulfide in the ball-milled slurry is less than 5 μm; dissolving a matrix in second water to obtain a matrix solution; the matrix comprises sodium carboxymethyl cellulose; subjecting the ball-milled slurry, a first surfactant and third water to high-speed shear homogenization to obtain a selenium disulfide slurry; mixing the selenium disulfide slurry and the matrix solution and subjecting the mixture to high-pressure homogenization to obtain a homogeneous slurry; adding a carbomer pre-dispersed liquid to the homogeneous slurry, then adding an inorganic alkaline solution to adjust the pH value to 6-7, and replenishing water to a formula amount to obtain the selenium disulfide lotion.

[0021] The present application introduces wet ball milling ultrafine selenium disulfide, ensures that the D90 particle size of selenium disulfide is less than 5 μm, significantly improves the dispersibility and suspension stability of selenium disulfide in the lotion, effectively avoids sedimentation, and improves the content uniformity; high-speed shearing and high-pressure homogenization are combined, the selenium disulfide is first made into selenium disulfide slurry through high-speed shearing, and then combined with high-pressure homogenization, further breaking the agglomeration, making the selenium disulfide particles uniformly dispersed in the system, and effectively inhibiting the stratification phenomenon. The present application optimizes the thickening system, uses sodium carboxymethyl cellulose and carbomer composite thickening, while ensuring appropriate viscosity, and gives the lotion better thixotropy and stability, avoiding excessive flow or excessive viscosity.

[0022] The selenium disulfide lotion prepared by the present application has the following beneficial effects:

[0023] The content uniformity is significantly improved: selenium disulfide micronization and efficient dispersion homogenization make the active ingredient more uniformly distributed in the lotion, ensuring the consistency of the therapeutic effect.

[0024] The stratification phenomenon is greatly improved: the optimized dispersion homogenization process and thickening system effectively inhibit the sedimentation and stratification of selenium disulfide.

[0025] The viscosity is appropriate and stable: the composite thickening system makes the lotion have good flowability when pouring, can be better attached to the skin after smearing, and the viscosity is stable during long-term storage.

[0026] The property is stable: the product appearance is uniform, there is no agglomeration or caking visible to the naked eye, and the color remains stable. BRIEF DESCRIPTION OF DRAWINGS

[0027] Figure 1 The shape evaluation photos of the selenium disulfide lotion prepared for the examples and comparative examples. DETAILED DESCRIPTION

[0028] The present application provides a preparation method of selenium disulfide lotion, comprising the following steps:

[0029] Wet ball milling selenium disulfide, first water and dispersant to obtain ball milling slurry; the D90 particle size of selenium disulfide in the ball milling slurry is less than 5 μm;

[0030] Dissolve the matrix in the second water to obtain a matrix solution; the matrix includes sodium carboxymethyl cellulose;

[0031] High-speed shearing homogenization treatment is performed on the ball milling slurry, the first surfactant and the third water to obtain selenium disulfide slurry;

[0032] After mixing the selenium disulfide slurry and the matrix solution, high-pressure homogenization treatment is performed to obtain a homogenized slurry;

[0033] The carbomer pre-dispersion liquid is added to the homogeneous slurry, and then an inorganic base solution is added to adjust the pH value to 6-7, and water is added to the formula amount to obtain a selenium disulfide lotion.

[0034] In the present invention, unless otherwise specified, all raw materials used are commercially available products well known in the art.

[0035] The present invention wet-ball-mills selenium disulfide, first water and a dispersant to obtain ball-milled slurry.

[0036] In the present invention, the mass ratio of the selenium disulfide to the first water is preferably 1:(5-10), and in specific embodiments, it can be 1:5, 1:8, or 1:10. In the present invention, the amount of the selenium disulfide used is determined according to the formula amount. The mass content of the selenium disulfide in the selenium disulfide lotion is preferably 1-3%, and in specific embodiments, it can be 1%, 1.5%, 2%, 2.5%, or 3%. In the present invention, the dispersant preferably includes polyvinyl alcohol. The present invention has no special requirements for the type of polyvinyl alcohol. Any polyvinyl alcohol known in the art that can be used as a dispersant can be used, such as polyvinyl alcohol 4000 and polyvinyl alcohol 3350.

[0037] In the present invention, the mass of the dispersant is preferably 0.05-2% of the mass of the selenium disulfide lotion, and in specific embodiments it can be 0.05%, 0.1%, 0.15% or 2%. In the present invention, the rotation speed of the wet ball milling is preferably 2000-4000rpm, and in specific embodiments it can be 2000rpm, 2500rpm, 3000rpm, 3500rpm or 4000rpm. The present invention has no special requirements for the time of the wet ball milling, as long as the D90 particle size of the selenium disulfide after wet ball milling is less than 5μm. In an embodiment of the present invention, after wet ball milling, it is preferably measured by a laser particle size analyzer to ensure that the D90 particle size is less than 5μm.

[0038] The invention significantly improves the dispersibility and suspension stability of selenium disulfide micropowder in the lotion after the selenium disulfide micropowder is processed by wet ball milling, effectively avoids sedimentation, and improves content uniformity.

[0039] The present invention dissolves the matrix in the second water to obtain a matrix solution.

[0040] In the present application, the matrix comprises sodium carboxymethyl cellulose, preferably further comprises a second surfactant and a humectant; the second surfactant preferably comprises one or more of sodium dodecyl sulfate, sodium laureth sulfate, disodium lauryl ether sulfosuccinate, ammonium lauryl sulfate, ammonium laureth sulfate and cocamidopropyl betaine, more preferably sodium dodecyl sulfate; the humectant preferably comprises one or more of glycerin, propylene glycol, butylene glycol, sodium hyaluronate and sorbitol, more preferably glycerin and propylene glycol. In the present application, the amount of the matrix is determined according to the formula amount. In terms of mass percentage, the selenium disulfide lotion comprises 10.5-15.5% of the matrix, more preferably comprises 7-9% of the second surfactant, 3.5-6.5% of the humectant and 0.4-0.6% of sodium carboxymethyl cellulose, and most preferably comprises 7-9% of sodium dodecyl sulfate, 2-4% of glycerin, 1.5-2.5% of propylene glycol and 0.4-0.6% of sodium carboxymethyl cellulose. In the present application, the second surfactant functions to give the selenium disulfide lotion good decontamination effect.

[0041] In specific embodiments, the content of sodium dodecyl sulfate can be 7%, 7.5%, 8%, 8.5% or 9%; the content of glycerin can be 2%, 3% or 4%; the content of propylene glycol can be 1.5%, 2% or 2.5%; and the content of sodium carboxymethyl cellulose can be 0.4%, 0.5% or 0.6%.

[0042] The present application does not have special requirements for the amount of the second water, which can completely dissolve the matrix. The present application does not have special requirements for the dissolution process, which can adopt the dissolution process well known in the art. In the embodiments of the present application, the matrix is added to a stainless steel reaction kettle equipped with a stirring device according to the ratio, an appropriate amount of second water is added, and stirring and dissolution are carried out at 30-50°C, with a stirring speed of 80-120 rpm, until the solution is transparent and clear.

[0043] After obtaining the ball milling slurry and the matrix solution, the present application subjects the ball milling slurry, the first surfactant and the third water to high-speed shearing homogenization treatment to obtain a selenium disulfide slurry.

[0044] In the present application, the first surfactant preferably comprises Tween, which preferably comprises Tween 80, and the mass content of the first surfactant in the selenium disulfide lotion is preferably 0.5-1%, which in specific embodiments can be 0.5% or 1%. The present application adds the first surfactant to improve the dispersibility of selenium disulfide. The present application does not have special requirements for the amount of the third water, which can normally be subjected to high-speed shearing homogenization treatment.

[0045] In the present application, the shearing speed of the high-speed shearing homogenization treatment is preferably 4000-6000 rpm, and in specific embodiments can be 4000 rpm, 4500 rpm, 5000 rpm, 5500 rpm or 6000 rpm; the shearing time is preferably 5-15 minutes, and in specific embodiments can be 5 minutes, 10 minutes or 15 minutes.

[0046] After obtaining the selenium disulfide slurry and the base solution, the present application mixes the selenium disulfide slurry and the base solution and then performs high-pressure homogenization treatment to obtain a homogenized slurry.

[0047] In the present application, the mixing preferably comprises slowly adding the selenium disulfide slurry to the base solution under continuous stirring. After the addition is complete, the present application preferably continues to stir for 20-40 minutes, and the stirring speed is preferably 60-100 rpm.

[0048] In the present application, the pressure of the high-pressure homogenization treatment is preferably 60-100 MPa, and in specific embodiments can be 60 MPa, 70 MPa, 80 MPa, 90 MPa or 100 MPa; the number of times of the high-pressure homogenization treatment is preferably 2-3 times. The present application makes the selenium disulfide into a selenium disulfide slurry through high-speed shearing, and further breaks the agglomeration by combining high-pressure homogenization, so that the selenium disulfide particles are uniformly dispersed in the system and the delamination phenomenon is effectively inhibited.

[0049] After obtaining the homogenized slurry, the present application adds a carbomer pre-dispersion liquid to the homogenized slurry, then adds an inorganic alkali solution to adjust the pH value to 6-7, and supplements water to the formulation amount to obtain a selenium disulfide lotion.

[0050] In the present application, the carbomer pre-dispersion liquid is preferably obtained by dispersing carbomer in water, and the mass ratio of carbomer to water in the carbomer pre-dispersion liquid is preferably 1:(15-25), and in specific embodiments can be 1:15, 1:20 or 1:25. In the present application, the carbomer preferably comprises carbomer 940 and / or carbomer 980. In the present application, the amount of carbomer is added according to the formulation amount, and the mass content of carbomer in the selenium disulfide lotion is preferably 0.3-0.4%, and in specific embodiments can be 0.3%, 0.35% or 0.4%. In the present application, the carbomer and sodium carboxymethyl cellulose act as a composite thickening agent to adjust the viscosity of the selenium disulfide lotion. In the present application, the sodium carboxymethyl cellulose is added first, which is conducive to improving the viscosity of the selenium disulfide during high-pressure homogenization treatment and improving the dispersion effect, while high-pressure homogenization will destroy the structure of the carbomer, causing the viscosity of the lotion to decrease, so the carbomer is added last.

[0051] In the present application, the inorganic alkali solution preferably comprises a hydroxide solution, and more preferably a sodium hydroxide solution, and the mass concentration of the sodium hydroxide solution is preferably 10%.

[0052] In the present application, the amount of the system obtained after adding the inorganic alkali solution to adjust the pH value can reach about 90% of the preparation amount, and the pH value will not change substantially after adding water to the formulation amount.

[0053] In the present application, the viscosity of the selenium disulfide lotion is preferably 200-800 mPa·s, and in specific embodiments, it can be 200 mPa·s, 300 mPa·s, 400 mPa·s, 500 mPa·s, 600 mPa·s, 700 mPa·s or 800 mPa·s.

[0054] The present application provides a selenium disulfide lotion prepared by the preparation method described in the above scheme, wherein the D90 of the selenium disulfide lotion is less than 5 μm.

[0055] The content uniformity of the selenium disulfide lotion prepared in the present application is significantly improved: the micronization and efficient dispersion of selenium disulfide make the active ingredient more uniformly distributed in the lotion, ensuring the consistency of the therapeutic effect. In the present application, the relative standard deviation of the selenium disulfide content at the top, middle and bottom of the selenium disulfide lotion is <1%.

[0056] The layering phenomenon of the selenium disulfide lotion prepared in the present application is greatly improved: the optimized dispersion and homogenization process and the thickening system effectively inhibit the sedimentation and layering of selenium disulfide. In the present application, the selenium disulfide lotion has no visible layering for 30 days, and the sedimentation volume percentage is maintained at more than 97%.

[0057] The viscosity of the selenium disulfide lotion prepared in the present application is suitable and stable: the composite thickening system makes the lotion have good flowability when pouring, and can better adhere to the skin after smearing, and the viscosity is stable during long-term storage.

[0058] The selenium disulfide lotion prepared in the present application has stable properties: the product appearance is uniform, and there is no visible agglomeration or caking, and the color remains stable.

[0059] The selenium disulfide lotion and the preparation method thereof provided in the present application will be described in detail below in conjunction with examples, but they should not be understood as limiting the scope of protection of the present application.

[0060] Examples 1-3

[0061] (1) Selenium disulfide micronization: Pharmaceutical grade selenium disulfide (CAS No.7446-34-6) purchased from Guangzhou Anxin Pharmaceutical Co., Ltd. (manufacturer: Macsen Drugs) was micronized by wet ball milling (ball mill: Wenzhou Qiangzhong Machinery Technology Co., Ltd. colloid mill, model: JM-L50). The selenium disulfide was mixed with purified water at a mass ratio of 1:5, and polyethylene glycol 4000 (purchased from Dow Chemical (China) Investment Co., Ltd.) was added, and the mixture was ground at a setting speed of 3000 rpm for 60 minutes. After grinding, it was determined by laser particle size analyzer (instrument: Malvern Mastersizer 3000 laser particle size analyzer, UK) to ensure that the D90 particle size was less than 5 μm.

[0062] (2) Preparation of the matrix:

[0063] Sodium dodecyl sulfate (purchased from BASF (China) Co., Ltd.), sodium carboxymethyl cellulose (purchased from Anhui Shanhe Pharmaceutical Auxiliary Co., Ltd.), glycerol (purchased from Hunan Jiudian Hongyang Pharmaceutical Co., Ltd.), and propylene glycol (purchased from Hunan Jiudian Hongyang Pharmaceutical Co., Ltd.) were added to a stainless steel reaction kettle equipped with a stirring device in the proportions specified in the formula. An appropriate amount of purified water was added, and the solution was dissolved at 40°C with stirring at a speed of 100 rpm until it was clear and transparent, resulting in a matrix solution.

[0064] (3) Preparation of selenium disulfide slurry:

[0065] The pretreated selenium disulfide powder was mixed with Tween 80 (purchased from Hubei Gedian Renfu Pharmaceutical Auxiliary Co., Ltd.) and part of the purified water in a certain proportion, and then sheared at 5000 rpm for 10 minutes by a high-shear homogenizer (equipment: Wuxi Yikai Automation Technology Co., Ltd., model: LR-5) to prepare a uniform selenium disulfide slurry.

[0066] (4) Mixing and homogenization:

[0067] The prepared selenium disulfide slurry was slowly added to the continuously stirred matrix solution. After the addition was complete, stirring was continued for 30 minutes at a speed of 80 rpm.

[0068] Subsequently, the mixture was passed through a high-pressure homogenizer (equipment: Doining Biological High-Pressure Homogenizer, model: AH-Basic) twice at a pressure of 80 MPa.

[0069] (5) Thickening and pH adjustment:

[0070] After homogenization, Carbopol 940 (purchased from Lubrizol Advanced Materials Corporation) pre-dispersion (mass ratio of Carbopol 940 to purified water is 1:20) was added, and the pH value was adjusted to 6.0-7.0 with 10% sodium hydroxide solution (purchased from National Pharmaceutical Group Chemical Reagent Co., Ltd.). Continuous stirring was carried out until the lotion viscosity reached the preset range.

[0071] (6) Water replenishment and packaging:

[0072] The final volume was made up with purified water, and after uniform stirring, filling was carried out.

[0073] Table 1 Formulation of selenium disulfide lotion of Examples 1-3 (% by mass)

[0074] Raw material name Example 1 Example 2 Example 3 Selenium disulfide 2.5 2.8 2.5 Polyethylene glycol 4000 0.1 0.1 0.1 Sodium dodecyl sulfate 8.0 8.0 7.5 Sodium carboxymethyl cellulose 0.5 0.5 0.5 Glycerin 3.0 3.0 3.0 Propylene glycol 2.0 2.0 1.8 Tween 80 1.0 1.0 1.0 Carbomer 940 0.3 0.35 0.3 10% sodium hydroxide solution Suitable amount Suitable amount Suitable amount Purified water Make up to 100 Make up to 100 Make up to 100

[0075] Comparative Example 1: Preparation of selenium disulfide lotion by conventional process

[0076] Main process differences:

[0077] Selenium disulfide pretreatment: No wet ball milling was carried out, only commercially available ordinary selenium disulfide powder was used.

[0078] Dispersion homogenization: Only conventional stirring dispersion was used, no high-speed shearing and high-pressure homogenization was carried out.

[0079] Thickening system: Only sodium carboxymethyl cellulose was used as thickening agent.

[0080] Specifically, the formulation is shown in Table 2. Sodium dodecyl sulfate, sodium carboxymethyl cellulose, glycerol and propylene glycol were added to purified water and stirred to dissolve. Selenium disulfide powder was directly added to the above solution, and Tween 80 was added while stirring. After stirring for 30 minutes, purified water was added to the final volume, the pH was adjusted, and filling was carried out.

[0081] Table 2 Formulation of selenium disulfide lotion of Comparative Example 1

[0082]

[0083]

[0084] Comparative Example 2: No high-speed shearing and high-pressure homogenization

[0085] Like the formulation of Example 1, the difference is that high-speed shearing and high-pressure homogenization are not used. The specific steps are as follows:

[0086] Selenium disulfide micronization: Refer to step (1) of Example 1.

[0087] Matrix preparation: Refer to step (2) of Example 1.

[0088] Mixing: In the continuously stirred base solution, the wet ball-milled selenium disulfide micro-powder was slowly added. After the addition was completed, the stirring was continued for 30 minutes at a stirring speed of 80 rpm.

[0089] Thickening and pH adjustment: Refer to step (5) of Example 1.

[0090] Water replenishment and packaging: Refer to step (6) of Example 1.

[0091] Comparative Example 3: No wet ball-milling

[0092] The difference from Example 1 is only that no wet ball-milling was performed, and the commercially available ordinary selenium disulfide powder was used directly.

[0093] The preparation steps are as follows:

[0094] Base preparation: Refer to step (2) of Example 1.

[0095] Selenium disulfide slurry preparation: The commercially available ordinary selenium disulfide powder without wet ball-milling was mixed with Tween 80 and part of purified water in a certain proportion, and a slurry was prepared by high-shear homogenizer at 5000 rpm for 10 minutes.

[0096] Mixing and homogenization: Refer to step (4) of Example 1.

[0097] Thickening and pH adjustment: Refer to step (5) of Example 1.

[0098] Water replenishment and packaging: Refer to step (6) of Example 1.

[0099] Comparative Example 4: Only a single thickening agent (carbomer 940) is used

[0100] The difference from Example 1 is only that the thickening system is different: only carbomer 940 is used as a thickening agent, while Example 1 uses a composite thickening of sodium hydroxymethyl cellulose and carbomer 940. All other process steps and material amounts remain consistent with Example 1, including micronization of selenium disulfide, high-speed shearing, and high-pressure homogenization.

[0101] Specifically, the preparation method is as follows:

[0102] Raw material pretreatment: Refer to step (1) of Example 1.

[0103] Base preparation: Sodium dodecyl sulfate, glycerol, and propylene glycol were added to a stainless steel reaction kettle equipped with a stirring device according to the formula proportion. An appropriate amount of deionized water was added, and the solution was dissolved at 40°C with stirring at a stirring speed of 100 rpm until the solution was clear and transparent.

[0104] Selenium disulfide slurry preparation: Refer to step (3) of Example 1.

[0105] Mixing and homogenization: refer to step (4) of Example 1.

[0106] Thickening and pH Adjustment: After homogenization, add Carbomer 940 pre-dispersion (Carbomer 940 to deionized water, mass ratio: 1:20) and adjust the pH to 6.0-7.0 with 10% sodium hydroxide solution. Continue stirring until the lotion viscosity reaches the preset range.

[0107] Rehydration and packaging: refer to step (6) of Example 1.

[0108] Table 3 Formula of Comparative Example 4

[0109] Raw material name Mass fraction (%) Selenium disulfide 2.5 Polyethylene glycol 4000 0.1 Sodium dodecyl sulfate 8.0 Sodium carboxymethyl cellulose 0 Glycerin 3.0 Propylene glycol 2.0 Tween 80 1.0 Carbomer 940 0.8 10% sodium hydroxide solution Suitable amount Purified water Make up to 100

[0110] Performance evaluation

[0111] In order to verify the advantages of the process of the present invention, various performance indicators of the selenium disulfide lotions prepared in Example 1 and Comparative Examples 1, 2 and 3 were compared.

[0112] 1. Trait evaluation

[0113] Method: Place the sample in a transparent glass bottle and visually inspect the lotion for color, uniformity, and the presence of stratification, lumps, or foreign matter at room temperature. Record the observations.

[0114] result:

[0115] Example 1: The orange-yellow uniform suspension was left for 48 hours without stratification, lumps, or foreign matter (such as Figure 1 (as shown in Example 1).

[0116] Example 2: The orange-yellow uniform suspension was left for 48 hours without stratification, lumps, or foreign matter (such as Figure 1 (as shown in Example 2).

[0117] Example 3: The orange-yellow uniform suspension was left for 48 hours without stratification, lumps, or foreign matter (such as Figure 1 (as shown in Example 3).

[0118] Comparative Example 1: The orange-yellow suspension was clearly stratified after being placed for 24 hours and was difficult to restore to uniformity after shaking (e.g. Figure 1 (as shown in Comparative Example 1).

[0119] Comparative Example 2: Orange-yellow suspension, after 48 hours of standing, slight stratification was observed, and after shaking, it could be basically restored to uniformity, but it was not as stable as Example 1 (e.g. Figure 1 (as shown in Comparative Example 2).

[0120] Comparative Example 3: Orange-yellow suspension, visible stratification after 24 hours of standing, good recovery of homogeneity after shaking, but less stable than Example 1 (as shown in Figure 1

[0121] Comparative Example 4: Orange-yellow suspension, no stratification initially, but stratification begins after 7 days of standing, and can be recovered to homogeneity after shaking, but at a slower rate than Example 1 (as shown in Figure 1

[0122] 2. Content uniformity determination

[0123] Method: Refer to the content determination method under the selenium disulfide lotion in the second part of the 2025 edition of the Chinese Pharmacopoeia. Three samples were taken from the top, middle and bottom of the bottle to determine the content of selenium disulfide in each part.

[0124] Results:

[0125] Example 1: Top content: 2.49%, middle content: 2.50%, bottom content: 2.51%. Relative standard deviation (RSD) 0.4%.

[0126] Example 2: Top content: 2.78%, middle content: 2.80%, bottom content: 2.81%. Relative standard deviation (RSD) 0.3%.

[0127] Example 3: Top content: 2.48%, middle content: 2.50%, bottom content: 2.52%. Relative standard deviation (RSD) 0.8%.

[0128] Comparative Example 1: Top content: 2.25%, middle content: 2.40%, bottom content: 2.80%. Relative standard deviation (RSD) 11.46%%.

[0129] Comparative Example 2: Top content: 2.35%, middle content: 2.45%, bottom content: 2.65%. Relative standard deviation (RSD) about 3.5%.

[0130] Comparative Example 3: Top content: 2.30%, middle content: 2.42%, bottom content: 2.70%. Relative standard deviation (RSD) about 5.0%.

[0131] Comparative Example 4: Top content: 2.40%, middle content: 2.50%, bottom content: 2.60%. Relative standard deviation (RSD) about 2.5%.

[0132] 3. Raw material particle size distribution determination

[0133] ​​Method: Take 1 g of selenium disulfide lotion, add water to dilute it to 10 ml, and use a laser particle size analyzer (instrument: Mastersizer 3000 laser particle size analyzer, Malvern, UK) to measure the particle size distribution (D10, D50, D90) of selenium disulfide particles.

[0134] result:

[0135] Example 1: D10 = 1.2 μm, D50 = 2.5 μm, D90 = 4.8 μm.

[0136] Example 2: D10 = 1.3 μm, D50 = 2.6 μm, D90 = 4.9 μm.

[0137] Example 3: D10 = 1.2 μm, D50 = 2.4 μm, D90 = 4.7 μm.

[0138] Comparative Example 1: D10 = 5.5 μm, D50 = 12.0 μm, D90 = 25.0 μm.

[0139] Comparative Example 2: D10 = 1.5 μm, D50 = 3.0 μm, D90 = 5.5 μm. The particle size after wet ball milling is smaller, but a small amount of agglomeration still exists due to the lack of subsequent homogenization.

[0140] Comparative Example 3: D10 = 3.0 μm, D50 = 7.0 μm, D90 = 15.0 μm. After homogenization, the particle size was reduced, but the effect was not as good as that of Example 1 due to the larger particle size of the initial raw material.

[0141] Comparative Example 4: D10 = 1.3 μm, D50 = 2.7 μm, D90 = 5.0 μm.

[0142] 4. Observation of stratification phenomenon

[0143] Methods: Samples were placed in 100 mL stoppered graduated cylinders and allowed to stand at room temperature. The sedimentation volume percentage (i.e., the percentage of the sedimentation layer to the total volume) and the height of the supernatant were observed and recorded daily for 30 consecutive days.

[0144] Instruments: 100 mL stoppered graduated cylinder, vernier caliper.

[0145] result:

[0146] Example 1: No stratification was visible to the naked eye within 30 days, and the sedimentation volume percentage remained above 98%.

[0147] Example 2: No stratification was visible to the naked eye within 30 days, and the sedimentation volume percentage remained above 98%.

[0148] Example 3: No visible stratification within 30 days, and the percentage of sedimentation volume remained above 97%.

[0149] Comparative Example 1: Obvious stratification started after 24 hours, and the percentage of sedimentation volume dropped to about 60% at 30 days, with a significant increase in supernatant.

[0150] Comparative Example 2: Slight stratification started after 48 hours, and the percentage of sedimentation volume dropped to about 85% at 30 days, with a stratification degree significantly less than that of Comparative Example 1, but still with a supernatant layer.

[0151] Comparative Example 3: Stratification started after 24 hours, and the percentage of sedimentation volume dropped to about 75% at 30 days, with a stratification degree between that of Comparative Example 1 and Comparative Example 2.

[0152] Comparative Example 4: Stratification started after 7 days, and the percentage of sedimentation volume was about 90% at 30 days.

[0153] 5. Viscosity determination

[0154] Method: Take an appropriate amount of lotion, and use a rotary viscometer (instrument: Brookfield DV-RV rotary viscometer, model: DV-RV) to determine the viscosity at 25°C, using an RV-4 rotor and at a rotation speed of 20 rpm.

[0155] Results:

[0156] Example 1: Viscosity: 500 ± 50 mPa·s.

[0157] Example 2: Viscosity: 500 ± 50 mPa·s.

[0158] Example 3: Viscosity: 500 ± 50 mPa·s.

[0159] Comparative Example 1: Viscosity: 800 ± 200 mPa·s (viscosity is too high, not easy to pour), and the viscosity dropped to about 300 mPa·s after one week, with poor stability.

[0160] Comparative Example 2: Viscosity: 500 ± 180 mPa·s, and the viscosity was stable after one week, but the suspension stability was not as good as Example 1.

[0161] Comparative Example 3: Viscosity: 400 ± 160 mPa·s, and the viscosity was stable after one week, but the particle sedimentation phenomenon was more obvious than Example 1.

[0162] Comparative Example 4: Viscosity: 480 ± 80 mPa·s, the initial viscosity was suitable, but the viscosity fluctuation range was larger after one week.

[0163] 6. Stability investigation

[0164] Method: The samples of Example 1 and Comparative Examples 1, 2 and 3 were placed under accelerated test conditions (40°C ± 2°C, relative humidity 25% ± 5%) and long-term test conditions (25°C ± 2°C, relative humidity 60% ± 5%), respectively. Samples were taken at the end of the 0th, 1st, 2nd, 3rd and 6th month to investigate changes in their properties, content uniformity, viscosity and pH value.

[0165] Instruments: constant temperature and humidity chamber (equipment: Shanghai Yiheng Scientific Instrument Co., Ltd., model: LRHS-150-L), pH meter (instrument: Mettler Toledo pH meter, model: SD-20).

[0166] Results (Summary of 6-month accelerated test data):

[0167] Example 1:

[0168] Properties: No obvious changes, no stratification or agglomeration.

[0169] Content uniformity: RSD value remained within 1.5%.

[0170] Viscosity: Maintain within the range of 400-600mPa·s.

[0171] pH value: Maintain within the range of 6.0-7.0.

[0172] Example 2:

[0173] Properties: No obvious changes, no stratification or agglomeration.

[0174] Content uniformity: RSD value remained within 2.0%.

[0175] Viscosity: Maintain within the range of 400-600mPa·s.

[0176] pH value: Maintain within the range of 6.0-7.0.

[0177] Example 3:

[0178] Properties: No obvious changes, no stratification or agglomeration.

[0179] Content uniformity: RSD value remained within 1.8%.

[0180] Viscosity: Maintain within the range of 400-600mPa·s.

[0181] pH value: Maintain within the range of 6.0-7.0.

[0182] Comparative Example 1:

[0183] Properties: Severe stratification occurs and it is difficult to restore uniformity after shaking.

[0184] Content uniformity: RSD value exceeded 10% in the third month.

[0185] Viscosity: decreased significantly, and was lower than 200mPa·s in the third month.

[0186] pH value: No significant change.

[0187] Comparative Example 2:

[0188] Properties: Moderate stratification occurred, but better than Comparative Example 1.

[0189] Content uniformity: RSD value was about 5% at the third month.

[0190] Viscosity: Remain relatively stable.

[0191] pH value: No significant change.

[0192] Comparative Example 3:

[0193] Properties: Moderate stratification occurred, but better than Comparative Example 1.

[0194] Content uniformity: RSD value was about 6% at the third month.

[0195] Viscosity: Remain relatively stable.

[0196] pH value: No significant change.

[0197] Comparative Example 4:

[0198] Properties: Slight delamination occurred, but better than Comparative Example 1.

[0199] Content uniformity: RSD value was approximately 3.0% at the third month.

[0200] Viscosity: Under accelerated conditions, the viscosity is in the range of 300-500 mPa·s. The viscosity decreases more significantly than that in Example 1, and the viscosity range changes more significantly, which is not as stable as in Example 1.

[0201] pH value: No significant change.

[0202] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for preparing a selenium disulfide lotion, characterized in that: The following steps are involved: Wet ball-milling selenium disulfide, the first water, and the dispersant to obtain a ball-milled slurry; wherein the D90 particle size of the selenium disulfide in the ball-milled slurry is less than 5 μm; dissolving a matrix in the second water to obtain a matrix solution; the matrix comprising sodium carboxymethyl cellulose; The ball-milled slurry, the first surfactant and the third water are subjected to high-speed shear homogenization treatment to obtain selenium disulfide slurry; The selenium disulfide slurry and the matrix solution are mixed and then subjected to high-pressure homogenization to obtain a homogeneous slurry; The carbomer pre-dispersion liquid is added to the homogeneous slurry, and then an inorganic base solution is added to adjust the pH value to 6-7, and water is added to the formula amount to obtain a selenium disulfide lotion.

2. The preparation method according to claim 1, characterized in that The shearing speed of the high-speed shear homogenization process is 4000-6000 rpm, and the shearing time is 5-15 minutes.

3. The preparation method according to claim 1, characterized in that The pressure of the high-pressure homogenization treatment is 60-100 MPa, and the number of times of the high-pressure homogenization treatment is 2-3 times.

4. The preparation method according to claim 1, characterized in that The dispersant includes polyvinyl alcohol; the rotation speed of the wet ball mill is 2000-4000 rpm.

5. The preparation method according to claim 1, characterized in that The matrix also includes a second surfactant and a humectant.

6. The preparation method according to claim 5, characterized in that The second surfactant includes one or more of sodium lauryl sulfate, sodium laureth sulfate, disodium laureth sulfosuccinate, ammonium lauryl sulfate, ammonium laureth sulfate and cocamidopropyl betaine; the moisturizer includes one or more of glycerin, propylene glycol, butylene glycol, sodium hyaluronate and sorbitol.

7. The preparation method according to claim 1, characterized in that Calculated by mass percentage, the selenium disulfide lotion comprises 1-3% of selenium disulfide, 0.05-2% of a dispersant, 10.5-15.5% of a base, 0.5-1% of a first surfactant, 0.3-0.4% of carbomer, an appropriate amount of an inorganic base and the balance of water; the content of the sodium carboxymethyl cellulose in the selenium disulfide lotion is 0.4-0.6%.

8. The preparation method according to claim 1, characterized in that The first surfactant includes Tween.

9. The preparation method according to claim 1, characterized in that The viscosity of the selenium disulfide lotion is 200-800 mPa·s.

10. The selenium disulfide lotion prepared by the preparation method according to any one of claims 1 to 9, characterized in that: The D90 of the selenium disulfide lotion is less than 5 μm.

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