A selenium disulfide detergent composition and its preparation method

Abstract

This invention belongs to the field of pharmaceutical preparations, specifically relating to a selenium disulfide detergent composition and its preparation method. The selenium disulfide detergent composition significantly improves the product's properties and quality uniformity by adjusting the amount and ratio of bentonite, the surfactant lauryl sulfate monoethanolamine salt, glyceryl monoricinoleate, and dodecyl-tetradecyl dimethyl betaine. Furthermore, the preparation process is simple, has high production efficiency, and is more suitable for industrial-scale mass production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparations, specifically relating to a selenium disulfide detergent composition and its preparation method. Background Technology

[0002] Seborrheic dermatitis (SD) is a common, chronic, relapsing, inflammatory skin disease that occurs on the basis of excessive sebum secretion. Its main clinical manifestations include oily scalp, folliculitis, scaling accompanied by itching, and even hair loss. Seborrheic dermatitis affects hundreds of millions of people worldwide. The "Expert Consensus on Scalp Health Management (2022)" clearly states that selenium sulfide shampoo can effectively inhibit fungal, bacterial, and parasitic infections of the scalp, while also significantly inhibiting scalp sebum secretion, helping to relieve inflammation and reduce scalp dandruff.

[0003] Selenium disulfide is highly hydrophobic, has poor dispersion uniformity, complex structure, and unstable performance. Moreover, it is easily oxidized and discolored under high temperature conditions, thus posing many technical challenges in its preparation.

[0004] CN117919099A discloses a selenium disulfide detergent and its preparation method. However, this formulation is complex and requires high-precision processing. It involves separately mixing a suspending agent, pH adjuster, thickener, and solvent to obtain mixture 1; mixing dodecyl-tetradecyl dimethyl betaine, selenium disulfide, and solvent to obtain mixture 2; mixing glyceryl monoricinoleate and lauryl sulfate monoethanolamine salt to obtain mixture 3; adding mixture 2 to mixture 3; and finally adding mixture 1, mixing, and homogenizing to obtain the selenium disulfide detergent. Furthermore, this process requires a preparation temperature of 50°C, at which selenium disulfide may exhibit stability issues.

[0005] CN114159322A discloses a selenium disulfide shampoo, which includes 27 components such as selenium disulfide, panthenol, salicylic acid, disodium EDTA, surfactant, hair conditioning agent, solvent, preservative and pH adjuster. The formula is complex and also contains irritating salicylic acid, panthenol and phenoxyethanol. Long-term use may cause skin irritation.

[0006] CN115887294A discloses a selenium disulfide shampoo containing 20 components, including a high molecular polymer, polyol, hyaluronic acid chloride, chelating agent, zinc salt, sunscreen, surfactant, antibacterial agent, and water. The formula is relatively complex, and the preparation process is complicated, requiring multiple cooling processes, which fails to completely solve the heat resistance problem of selenium disulfide shampoo.

[0007] In summary, there is still a need to develop a new selenium disulfide detergent composition that is stable in quality and has a simple process. Summary of the Invention

[0008] To address the shortcomings of existing technologies, this invention provides a novel selenium disulfide detergent composition and its preparation method. By adjusting the amount and ratio of bentonite and surfactants lauryl sulfate monoethanolamine salt, glyceryl monoricinoleate, and dodecyl-tetradecyl dimethyl betaine, the composition significantly improves the uniformity of product properties and quality. It not only exhibits small batch-to-batch variations and good long-term stability, but also boasts a simple preparation process, high production efficiency, and is more suitable for industrial-scale mass production.

[0009] Specifically, the selenium disulfide detergent composition of the present invention, calculated by the mass-volume ratio (w / v) of the composition, comprises:

[0010] Selenium disulfide 2.0-3.0%

[0011] Bentonite 1.0-4.0%

[0012] Surfactant 10.0-26.0%

[0013] Colorant 0.5-1.5%

[0014] Thickener 0.1-0.5%

[0015] Fragrance 0.01-1.0%

[0016] pH adjuster, adjust pH to 3.0-5.0.

[0017] and / or other pharmaceutically acceptable excipients, and the remainder water;

[0018] The surfactant is a combination of lauryl sulfate monoethanolamine salt, ricinoleate monoglyceride, and dodecyl-tetradecyl dimethyl betaine, and the mass ratio of bentonite: lauryl sulfate monoethanolamine salt: ricinoleate monoglyceride: dodecyl-tetradecyl dimethyl betaine is 1:(4.00-8.80):(0.38-0.80):(0.60-1.50).

[0019] Preferably, the mass ratio of bentonite: lauryl sulfate monoethanolamine salt: ricinoleic acid glyceride: dodecyl-tetradecyl dimethyl betaine is 1:(5.00-8.70):(0.45-0.75):(0.72-1.46), and more preferably 1:(5.70-6.10):(0.45-0.55):(0.80-1.00).

[0020] Preferably, based on the composition's mass-to-volume ratio (w / v), the amount of lauryl sulfate monoethanolamine salt is 8.0-20.0%, the amount of ricinoleate monoglyceride is 0.8-2.0%, and the amount of dodecyl-tetradecyl dimethyl betaine is 1.2-4.0%. Further, the amount of lauryl sulfate monoethanolamine salt is 9.0-17.0%, the amount of ricinoleate monoglyceride is 1.0-1.6%, and the amount of dodecyl-tetradecyl dimethyl betaine is 1.6-3.2%.

[0021] Preferably, the amount of bentonite used is 1.5-2.8% based on the mass-volume ratio (w / v) of the composition, more preferably 1.5-2.4%.

[0022] Preferably, the colorant is selected from any one or a combination of titanium dioxide, zinc oxide, talc, and kaolin, and is further selected from titanium dioxide.

[0023] Preferably, the thickener is selected from any one or a combination of sodium chloride, potassium chloride, ammonium chloride, and monoethanolamine chloride, and is further selected from sodium chloride.

[0024] Preferably, the pH adjuster is selected from any one or a combination of sodium dihydrogen phosphate, sodium dihydrogen phosphate, citric acid, sodium hydroxide, sorbic acid, and sodium bicarbonate, and is further selected from a combination of sodium dihydrogen phosphate and citric acid; wherein the sodium dihydrogen phosphate includes anhydrous form and hydrate.

[0025] Preferably, the flavoring is selected from any one or a combination of strawberry flavoring, cherry flavoring, lemon flavoring, and sweet orange flavoring.

[0026] Preferably, the pH adjuster adjusts the pH to 4.0-5.0, more preferably 4.0-4.5.

[0027] Preferably, the viscosity of the selenium disulfide detergent is 500-2000 mPa·s, further 700-1800 mPa·s, and more preferably 1000-1400 mPa·s.

[0028] Preferably, the compositions of the present invention may optionally contain other pharmaceutically acceptable excipients, such as solubilizers, chelating agents, preservatives, antioxidants, thickeners, buffers, stabilizers, etc.

[0029] Further, based on the composition's mass-to-volume ratio (w / v), the composition comprises:

[0030] Selenium disulfide 2.3-2.7%

[0031] Bentonite 1.0-3.5%

[0032] Lauryl sulfate monoethanolamine salt 8.0-20.0%

[0033] 0.8-1.8% ricinoleate monoester

[0034] Dodecyl-tetradecyl dimethyl betaine 1.3-3.6%

[0035] Titanium dioxide 0.8-1.2%

[0036] Sodium chloride 0.2-0.5%

[0037] Fragrance 0.1-1.0%

[0038] pH adjuster, adjust pH to 3.0-5.0.

[0039] And the remaining water.

[0040] The mass ratio of bentonite: lauryl sulfate monoethanolamine salt: ricinoleic acid glyceride: dodecyl-tetradecyl dimethyl betaine is 1:(4.00-8.80):(0.38-0.80):(0.60-1.50); ​​the pH adjuster is a combination of sodium dihydrogen phosphate and citric acid.

[0041] Further, the mass ratio of bentonite: lauryl sulfate monoethanolamine salt: ricinoleic acid glyceride: dodecyl-tetradecyl dimethyl betaine is 1:(5.00-8.70):(0.45-0.75):(0.72-1.46), more preferably 1:(5.70-6.10):(0.45-0.55):(0.80-1.00).

[0042] Furthermore, the selenium disulfide content is 2.4-2.6%, more preferably 2.5%, calculated based on the composition's mass-to-volume ratio (w / v).

[0043] Furthermore, the bentonite content, calculated by the mass-volume ratio (w / v) of the composition, is 1.5-2.4%, more preferably 2.0-2.4%, and most preferably 2.2%.

[0044] Further, the lauryl sulfate monoethanolamine salt is 9-17% by weight-volume ratio (w / v) of the composition, more preferably 11-15%, and most preferably 13%.

[0045] Further, the glyceryl monoricinoleate is 1.0-1.6%, more preferably 1.0-1.3%, and most preferably 1.1%, calculated by the mass-volume ratio (w / v) of the composition.

[0046] Further, the dodecyl-tetradecyl dimethyl betaine is 1.6-3.2% by weight-volume ratio (w / v) of the composition, more preferably 1.8-2.2%, and most preferably 2%.

[0047] Further, based on the mass-volume ratio (w / v) of the composition, the sodium dihydrogen phosphate is 0.2-0.5% and the citric acid is 0.4-0.7%; more preferably, the sodium dihydrogen phosphate is 0.3-0.4% and the citric acid is 0.5-0.6%.

[0048] Further, based on the composition's mass-to-volume ratio (w / v), the titanium dioxide is 0.9-1.1%, the sodium chloride is 0.2-0.4%, and the fragrance is 0.1-0.5%.

[0049] This invention also provides a method for preparing a selenium disulfide detergent composition, the method comprising the following steps:

[0050] At room temperature, bentonite is swollen in water, then selenium disulfide is added for dispersion, followed by the addition of colorant, surfactant, thickener, pH adjuster, fragrance, and water, and the mixture is stirred until homogeneous to obtain selenium disulfide detergent.

[0051] Preferably, the preparation method includes the following steps:

[0052] At room temperature, bentonite is swollen in water, then selenium disulfide is added for dispersion, followed by titanium dioxide and citric acid, and then lauryl sulfate monoethanolamine salt, glyceryl monoricinoleate, and dodecyl-tetradecyl dimethyl betaine are added sequentially and mixed. Finally, fragrance, sodium chloride solution, and sodium dihydrogen phosphate solution are added and mixed to obtain selenium disulfide detergent.

[0053] Preferably, the room temperature is 10-30°C, more preferably 20-30°C, and even more preferably 20-25°C.

[0054] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0055] 1. This invention has surprisingly discovered that, in selenium disulfide detergents, the unique multidimensional structure of bentonite and the suspending properties of surfactants can achieve an unexpected synergistic effect under specific dosage and ratio. This not only effectively solves the problems of dispersion uniformity and stability caused by the strong hydrophobicity of selenium disulfide, but also solves the problem of large batch-to-batch differences in existing selenium disulfide detergents, resulting in superior product rheological properties.

[0056] 2. Based on the optimized formulation, this invention further simplifies the preparation process of selenium disulfide detergent, enabling it to be prepared at room temperature. This process not only avoids the risk of selenium disulfide oxidizing and discoloring at high temperatures, but also effectively balances the slow swelling rate of bentonite at low temperatures and the tendency of surfactants to foam at high temperatures. This greatly improves the production efficiency of the product, reduces the preparation cost, and has high process reproducibility, making it more conducive to commercial mass production. Attached Figure Description

[0057] Figure 1 Flow curve comparison chart of Example 1 and multiple batches of Comparative Example 1.

[0058] Figure 2 Comparison of flow curves between Comparative Example 1 and multiple batches of Example 1. Detailed Implementation

[0059] The present invention is further illustrated below by way of embodiments, but these embodiments are not intended to limit the invention to the scope of the embodiments described. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0060] In this document, unless otherwise specified, the proportions referred to are as follows: weight percentage (w / w) is the percentage of the weight of each component to the total weight of the composition; volume percentage (v / v) is the percentage of the volume of each component to the total volume of the composition; mass-volume ratio (w / v) is the percentage of the weight of each component to the total volume of the composition; and volume-mass ratio (v / w) is the percentage of the volume of each component to the total weight of the composition.

[0061] Unless otherwise stated, the material information for the following embodiments and comparative examples is all commercially available.

[0062] Example 1: Selenium disulfide detergent

[0063] Table 1 Selenium disulfide lotion formula 1

[0064]

[0065] Prescription preparation process:

[0066] (1) Bentonite swelling: At room temperature, add bentonite to an appropriate amount of purified water, turn on stirring / homogenization, and after the bentonite has fully swelled, add selenium disulfide raw material, vacuum to -0.08 to -0.10 MPa, turn on homogenization and stirring until the selenium disulfide is completely dispersed, and obtain mixture A;

[0067] (2) Mixing: At room temperature, first add titanium dioxide and citric acid to mixture A and stir until homogeneous. Then, add the prescribed amounts of lauryl sulfate monoethanolamine salt, ricinoleic acid glyceride, and dodecyl-tetradecyl dimethyl betaine in sequence. Stir until homogeneous. Finally, add the prescribed amounts of fragrance, sodium chloride solution, and sodium dihydrogen phosphate monohydrate solution and stir until homogeneous to obtain mixture B, which is the liquid to be filled.

[0068] (3) Filling: At room temperature, the mixture B is transferred in batches for filling. During filling, the liquid in the mixing tank is kept under vacuum at -0.08 to -0.10 MPa and stirred at low speed. The selenium disulfide detergent is obtained after filling.

[0069] Example 2: Study on the dosage of bentonite

[0070] Table 2 Selenium disulfide formulations 2-1 to 2-6

[0071]

[0072] The prescription preparation process is the same as in Example 1.

[0073] Example 3: Study on the dosage of lauryl sulfate monoethanolamine salt

[0074] Table 3 Selenium disulfide formulations 3-1 to 3-6

[0075]

[0076]

[0077] The prescription preparation process is the same as in Example 1.

[0078] Example 4: Study on the dosage of glyceryl monoricinoleate

[0079] Table 4 Selenium disulfide formulations 4-1 to 4-6

[0080]

[0081]

[0082] The prescription preparation process is the same as in Example 1.

[0083] Example 5: Study on the dosage of dodecyl-tetradecyldimethylbetaine

[0084] Table 5 Selenium disulfide formulations 5-1 to 5-6

[0085]

[0086] The prescription preparation process is the same as in Example 1.

[0087] Comparative Example 1: A commercially available selenium disulfide lotion, marketed under the brand name Selsun, produced by Opella Healthcare France Sas.

[0088] Example 6: Quality Testing of Selenium Disulfide Detergent

[0089] The selenium disulfide detergents of Examples 1-5 and the commercially available detergent of Comparative Example 1 were tested for key product quality indicators. The testing scheme is shown below, and the test results are detailed in Table 6.

[0090] (1) Sedimentation volume ratio: Refer to General Chapter 0123 of the 2020 edition of the Chinese Pharmacopoeia. Measure 50 ml of the test sample using a stoppered graduated cylinder, seal tightly, shake vigorously for 1 minute, and record the initial height H0 of the suspension. Let stand for 3 hours and record the final height H of the suspension. Sedimentation volume ratio = H / H0. The sedimentation volume ratio should not be less than 0.90.

[0091] (2) Viscosity: Viscosity was measured using a Boller Fly DV2TRVTJ0 viscosity measuring instrument; Rotor: #21; Rotation speed: 20rpm; Test time: 1min; Test temperature: 25±0.2℃.

[0092] (3) Settling time: Measure 50ml of the test sample into a stoppered graduated cylinder, stopper it tightly, shake it vigorously for 1 minute, and observe the characteristics of the sample after settling. When a clear and transparent liquid appears in the upper layer, it is considered to have separated into layers.

[0093] Table 6. Detergent quality test results for each embodiment and comparative example.

[0094]

[0095]

[0096] According to the results in the table above, when bentonite and surfactants such as lauryl sulfate monoethanolamine salt, glyceryl monoricinoleate, and dodecyl-tetradecyl dimethyl betaine are combined in a specific ratio, the resulting selenium disulfide detergents are all orange-yellow viscous suspensions with superior product properties, moderate viscosity, good uniformity, and are not prone to stratification, such as formulations 1, 2-2, 2-3, and 3-4.

[0097] Both excessively high and low ratios of bentonite and surfactant can reduce product quality. An improper ratio can lead to rapid layering and poor suspension in the resulting selenium sulfide lotion, as seen in formulations 2-1, 3-1, and 4-1. This makes it difficult for patients to mix the lotion evenly, resulting in uneven selenium sulfide concentration distribution and reduced efficacy. An inappropriate ratio can also lead to excessively high viscosity of the selenium sulfide, as seen in formulations 2-6, 4-6, and 5-5. This reduces the product's spreadability and overall user experience.

[0098] It is evident that the appropriate ratio of bentonite to surfactants such as lauryl sulfate monoethanolamine salt, glyceryl monoricinoleate, and dodecyl-tetradecyl dimethyl betaine is crucial to the quality of selenium disulfide detergent.

[0099] Example 7: Stability Test of Selenium Disulfide Detergent

[0100] Accelerated stability tests were conducted on the selenium disulfide detergents of Example 1 and Comparative Example 1. The specific conditions were: 30 days at 50°C and 6 months at 40°C. The properties, pH value, content, sedimentation volume ratio and viscosity of the samples were measured at the corresponding time points. The test results are shown in the table below.

[0101] Content determination method: Take selenium disulfide detergent, shake well, accurately weigh an appropriate amount (approximately equivalent to 0.1 g of selenium disulfide), add 25 ml of fuming nitric acid, heat in a water bath for 2 hours, cool, transfer to a 100 ml volumetric flask, dilute with water to the mark, shake well, filter, accurately measure 20 ml of the filtrate, add 10 g of urea and 25 ml of water, heat to boiling, cool, add 10 ml of potassium iodide test solution and 3 ml of starch indicator solution, and immediately titrate with sodium thiosulfate solution (0.05 mol / L). Titrate until the solution changes from reddish-brown to orange-red. Each 1 ml of sodium thiosulfate titrant (0.05 mol / L) is equivalent to 1.789 mg of SeS2. Calculate the selenium disulfide content in the sample according to the formula.

[0102] Table 7. Stability test results of Example 1 and Comparative Example 1

[0103]

[0104]

[0105] According to the results in the table above, the selenium disulfide detergent prepared in Example 1 maintained essentially unchanged properties, pH, content, sedimentation volume ratio, and viscosity after being placed at 50℃ for 30 days and at 40℃ for 6 months, demonstrating good long-term stability. In contrast, the selenium disulfide content in the formulation of Comparative Example 1 fluctuated significantly under high-temperature conditions, indicating that the content stability of commercially available selenium disulfide detergents is relatively poor, possibly due to unstable production processes.

[0106] Example 8: Rheological property testing of selenium disulfide detergent

[0107] Selenium disulfide detergent is a shear-thinning semi-fluid formulation with a certain viscosity. Its rheological properties reflect the product's stability and performance: at low shear rates, the viscosity value indirectly reflects the product's stability; generally, the higher the viscosity, the more stable the quality. At high shear rates, the viscosity value indirectly reflects the product's user experience; appropriately reducing viscosity is beneficial for product extrusion and application, as well as providing better spreadability and comfort.

[0108] Rheological curves of multiple batches of Comparative Examples 1 (Comparative Examples 1-1, 1-2, 1-3) and multiple batches of Example 1 (Examples 1-1, 1-2, 1-3) were respectively tested. The test comparison results are shown in [Figure 1]. Figure 1 and 2 .

[0109] Figure 1 The rheological curves show that there are significant batch-to-batch differences in Comparative Example 1 (commercially available reference preparation), indicating that its formulation or process control is fluctuating and the process reproducibility is poor. Example 1 is within the numerical range of multiple batches of Comparative Example 1, indicating that the rheological properties of Example 1 are similar to those of Comparative Example 1. Figure 2 The rheological curves show that the selenium disulfide detergent prepared in Example 1 exhibits highly overlapping rheological curves in different batches, indicating that it has superior process reproducibility and formulation stability.

Claims

1. A selenium disulfide detergent composition, characterized in that, The composition comprises, based on the composition's mass-to-volume ratio (w / v): Selenium disulfide 2.0-3.0% Bentonite 1.0-4.0% Surfactant 10.0-26.0% Colorant 0.5-1.5% Thickener 0.1-0.5% Fragrance 0.01-1.0% pH adjuster, adjust pH to 3.0-5.

0. and / or other pharmaceutically acceptable excipients, and the remainder water; The surfactant is a combination of lauryl sulfate monoethanolamine salt, ricinoleate monoglyceride, and dodecyl-tetradecyl dimethyl betaine, and the mass ratio of bentonite: lauryl sulfate monoethanolamine salt: ricinoleate monoglyceride: dodecyl-tetradecyl dimethyl betaine is 1:(4.00-8.80):(0.38-0.80):(0.60-1.50).

2. The selenium disulfide detergent composition according to claim 1, characterized in that, The amount of lauryl sulfate monoethanolamine salt used is 8.0-20.0%, the amount of ricinoleate monoglyceride is 0.8-2.0%, and the amount of dodecyl-tetradecyl dimethyl betaine is 1.2-4.0%.

3. The selenium disulfide detergent composition according to any one of claims 1-2, characterized in that, The mass ratio of bentonite: lauryl sulfate monoethanolamine salt: ricinoleic acid glyceride: dodecyl-tetradecyl dimethyl betaine is 1:(5.00-8.70):(0.45-0.75):(0.72-1.46).

4. The selenium disulfide detergent composition according to any one of claims 1-3, characterized in that, The amount of bentonite used is 1.5-2.8%.

5. The selenium disulfide detergent composition according to any one of claims 1-3, characterized in that, The colorant is selected from any one or a combination of titanium dioxide, zinc oxide, talc, and kaolin. The thickener is selected from any one or a combination of sodium chloride, potassium chloride, ammonium chloride, and monoethanolamine chloride; The pH adjuster is selected from any one or a combination of sodium dihydrogen phosphate, sodium dihydrogen phosphate, citric acid, sodium hydroxide, sorbic acid, and sodium bicarbonate.

6. The selenium disulfide detergent composition according to any one of claims 1-3, characterized in that, The viscosity of the selenium disulfide detergent is 500-2000 mPa·s, preferably 700-1800 mPa·s.

7. The selenium disulfide detergent composition according to claim 1, characterized in that, The composition comprises, based on the composition's mass-to-volume ratio (w / v): Selenium disulfide 2.3-2.7% Bentonite 1.0-3.5% Lauryl sulfate monoethanolamine salt 8.0-20.0% 0.8-1.8% ricinoleate monoester Dodecyl-tetradecyl dimethyl betaine 1.3-3.6% Titanium dioxide 0.8-1.2% Sodium chloride 0.2-0.5% Fragrance 0.1-1.0% pH adjuster, adjust pH to 3.0-5.

0. And the remaining water. The mass ratio of bentonite: lauryl sulfate monoethanolamine salt: ricinoleic acid glyceride: dodecyl-tetradecyl dimethyl betaine is 1:(4.00-8.80):(0.38-0.80):(0.60-1.50); ​​the pH adjuster is a combination of sodium dihydrogen phosphate and citric acid.

8. The selenium disulfide detergent composition according to claim 7, characterized in that, Based on the mass-volume ratio (w / v) of the composition, the selenium disulfide is 2.4-2.6%, bentonite is 1.5-2.4%, lauryl sulfate monoethanolamine salt is 9-17%, ricinoleic acid glyceride is 1.0-1.6%, dodecyl-tetradecyl dimethyl betaine is 1.6-3.2%, titanium dioxide is 0.9-1.1%, sodium chloride is 0.2-0.4%, and fragrance is 0.1-0.5%.

9. A method for preparing a selenium disulfide detergent composition according to any one of claims 1-8, characterized in that, The preparation method includes the following steps: At room temperature, bentonite is swollen in water, then selenium disulfide is added for dispersion, followed by the addition of colorant, surfactant, thickener, pH adjuster, fragrance, and water, and the mixture is stirred until homogeneous to obtain selenium disulfide detergent.

10. The preparation method according to claim 9, characterized in that, The preparation method includes the following steps: At room temperature, bentonite is swollen in water, then selenium disulfide is added for dispersion, followed by titanium dioxide and citric acid, and then lauryl sulfate monoethanolamine salt, ricinoleic acid glyceride, and dodecyl-tetradecyl dimethyl betaine are added in sequence and mixed. Finally, fragrance, sodium chloride solution, and sodium dihydrogen phosphate solution are added and mixed to obtain selenium disulfide detergent. Preferably, the room temperature is 10-30°C.

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