Gel and preparation method thereof

Abstract

The invention relates to a gel and a preparation method thereof, in particular to a selenium disulfide gel. The selenium disulfide gel comprises selenium disulfide, a sun-screening agent, an ion regulator, a gel matrix, a humectant, a pH regulator and purified water. The selenium disulfide gel is made of materials with good biocompatibility, skin irritation is reduced, patient compliance and safety are improved, and the gel is convenient to store, transport and carry and is more convenient.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations, and particularly relates to a selenium disulfide gel and a preparation method thereof. Background Art

[0002] Seborrheic dermatitis is a chronic inflammatory skin disease. The causes are diverse and may be closely related to genetic factors, microbial infection (such as Malassezia), food habits, increased sebum secretion caused by certain diseases, neurological dysfunction, immune dysfunction, etc. At present, the drugs used to treat seborrheic dermatitis include glucocorticoid preparations, calcineurin inhibitors, antibacterial preparations, etc.

[0003] Atopic dermatitis is a common chronic, recurrent, inflammatory skin disease. At present, the cause of atopic dermatitis is not fully understood, and it may be related to multiple factors such as genetic factors, environmental factors, and immune system abnormalities. In the past 30 years, the incidence of atopic dermatitis has been gradually increasing worldwide. Currently, the main treatment drugs are also concentrated in glucocorticoids, calcineurin inhibitors, antibacterial drugs, etc.

[0004] Pityriasis versicolor, also known as tinea versicolor or tinea versicolor, is a chronic superficial fungal infection of the skin caused by the fungus Malassezia. The pathogen is present on the skin of most people, but the onset of pityriasis versicolor is usually caused by the interaction of genetic predisposition and environmental factors, such as hot and humid environments, excessive skin oil secretion, and the use of immunosuppressants. The main treatment is topical antifungal drugs, such as related imidazoles and allylamines.

[0005] Selenium disulfide has the effects of anti-seborrhea, inhibiting Malassezia, and anti-epidermal hyperplasia. It is widely used in the treatment of dandruff, seborrheic dermatitis, pityriasis versicolor, and atopic dermatitis. At present, the only selenium disulfide preparation on the market is lotion with a concentration of 2.5%, but the lotion contains a large amount of surfactants, which will cause obvious irritation to patients with sensitive skin if used for a long time.

[0006] Therefore, there is an urgent need in the art for a selenium disulfide preparation that can reduce skin irritation and improve patient compliance and safety. Summary of the invention

[0007] To solve the above problems, the present invention provides a selenium disulfide gel, which can reduce skin irritation, improve patient compliance and safety, and the gel of the present invention is easy to store, transport and carry.

[0008] In a first aspect of the present invention, a selenium disulfide gel is provided, wherein the selenium disulfide gel comprises selenium disulfide, a sunscreen, a gel base, a moisturizer, a pH regulator and purified water;

[0009] Wherein, the gel matrix is ​​selected from the group consisting of xanthan gum, carbomer, sodium carboxymethyl cellulose;

[0010] The mass ratio of selenium disulfide to the gel matrix is ​​1:(0.1-10).

[0011] In another preferred embodiment, the sunscreen agent is titanium dioxide, zinc oxide, or terephthalylidene dicamphor sulfonic acid.

[0012] In another preferred embodiment, the gel matrix is ​​xanthan gum.

[0013] In another preferred embodiment, the mass ratio of selenium disulfide to the gel matrix is ​​1:(0.5-8), preferably 1:(0.5-5), and more preferably 1:(1-4).

[0014] In a preferred example, the pH adjuster is citric acid and / or sodium hydroxide.

[0015] In a preferred embodiment, the moisturizing agent is selected from the following group: glycerin, propylene glycol, and sodium hyaluronate.

[0016] In another preferred embodiment, the humectant is glycerin.

[0017] In a preferred example, the pH range of the gel is 2.0 to 5.0, preferably 3.0 to 5.0, and more preferably 3.5 to 5.0.

[0018] In a preferred embodiment, the gelling agent further contains an ion regulator.

[0019] In another preferred embodiment, the gel is composed of selenium disulfide, a sunscreen, a gel base, a pH adjuster, purified water and a moisturizer.

[0020] In another preferred embodiment, the gel is composed of selenium disulfide, a sunscreen, a gel base, a pH regulator, purified water, a moisturizer and an ion regulator.

[0021] In a preferred embodiment, the ion regulator is selected from the following group: sodium chloride, sodium dihydrogen phosphate, and sodium citrate.

[0022] In another preferred embodiment, the ion regulator is sodium chloride.

[0023] In a preferred example, the gel comprises 1.0-2.0 parts by weight of selenium disulfide, 0.1-5.0 parts by weight of sunscreen, 0.1-8.0 parts by weight of gel base, 2-20 parts by weight of moisturizer, and 80-98 parts by weight of pH adjuster and purified water.

[0024] In a preferred embodiment, the gelling agent further comprises 0 to 5 parts by weight of an ion regulator.

[0025] In another preferred embodiment, the gelling agent comprises 1.0 to 1.9 parts by weight of selenium disulfide, preferably 1.0 to 1.7 parts by weight, and more preferably 1.0 to 1.5 parts by weight.

[0026] In another preferred embodiment, the gel comprises 0.1 to 3.0 parts by weight of a sunscreen, preferably 0.1 to 1.0 parts by weight, and more preferably 0.1 to 0.5 parts by weight.

[0027] In another preferred embodiment, the gelling agent comprises 0.5 to 5.0 parts by weight of the gel matrix, preferably 1.0 to 4.0 parts by weight, and more preferably 1.0 to 2.0 parts by weight.

[0028] In another preferred embodiment, the gel comprises 2 to 15 parts by weight of the moisturizer, preferably 2 to 10 parts by weight, and more preferably 5.0 to 10.0 parts by weight.

[0029] In another preferred embodiment, the gelling agent comprises 82 to 96 parts by weight of the pH adjusting agent and purified water, preferably 84 to 95 parts by weight, and more preferably 85 to 93 parts by weight.

[0030] In another preferred embodiment, the gelling agent comprises 0 to 4 parts by weight of the ion regulator, preferably 0 to 3 parts by weight, and more preferably 0 to 1 part by weight.

[0031] In another preferred embodiment, the selenium disulfide accounts for 0.25-2.0wt% of the total weight of the gel, preferably 0.5-2wt%, more preferably 0.5-1.5wt%, and most preferably 0.8-1.2wt%.

[0032] In another preferred embodiment, the selenium disulfide accounts for 1.0 to 1.9 wt %, preferably 1.0 to 1.7 wt %, and more preferably 1.0 to 1.5 wt % of the total weight of the gel.

[0033] In another preferred embodiment, the sunscreen agent accounts for 0.1 to 3.0 wt %, preferably 0.1 to 1.0 wt %, and more preferably 0.1 to 0.5 wt % of the total weight of the gel.

[0034] In another preferred embodiment, the gel matrix accounts for 0.5-5.0 wt %, preferably 1.0-4.0 wt %, and more preferably 1.0-2.0 wt % of the total weight of the gel.

[0035] In another preferred embodiment, the humectant accounts for 2 to 15 wt %, preferably 2 to 10 wt %, and more preferably 5.0 to 10.0 wt % of the total weight of the gel.

[0036] In another preferred embodiment, the pH regulator and purified water account for 82-96 wt %, preferably 84-95 wt %, and more preferably 85-93 wt % of the total weight of the gelling agent.

[0037] In another preferred embodiment, the ion regulator accounts for 0 to 4 wt %, preferably 0 to 3 wt %, and more preferably 0 to 1 wt % of the total weight of the gelling agent.

[0038] In another preferred embodiment, the selenium disulfide has a D 90 It is 4 to 15 μm, preferably 4.0 to 7.0 μm.

[0039] In another preferred embodiment, the selenium disulfide has a D 90 Achieved by ball milling for ≥ 3h.

[0040] In another preferred embodiment, the selenium disulfide has a D 90 This is achieved by ball milling for 3 to 10 hours.

[0041] The second aspect of the present invention provides a use of the gel according to the first aspect of the present invention for preparing a medicament for preventing or treating atopic dermatitis.

[0042] According to a third aspect of the present invention, there is provided a method for preparing the gel according to the first aspect of the present invention, comprising the following steps:

[0043] 1) suspending selenium disulfide and sunscreen in water and performing ball milling;

[0044] 2) adding gel matrix and optional ion regulator, and stirring;

[0045] 3) Add moisturizer and stir;

[0046] 4) Add a pH adjuster to adjust the pH to 2.0-5.0, add purified water, and stir;

[0047] 5) Fill into ointment tube and seal.

[0048] In another preferred embodiment, the ball milling time in step 1 is 3 to 10 hours, preferably 3 to 7 hours.

[0049] In another preferred embodiment, step 2 further comprises the following steps: adding gel matrix and ion regulator, and homogenizing and dispersing them using a high-pressure homogenizer.

[0050] In another preferred embodiment, the speed of the homogenizing and dispersing in step 2 is 8000-12000 r / min, and the time is 10-20 min.

[0051] In another preferred embodiment, in step 3, stirring is performed under a vacuum degree of -0.1 MPa to -0.05 MPa, preferably -0.08 MPa to -0.05 MPa.

[0052] In another preferred embodiment, the stirring time in step 3 is 1 to 4 hours, preferably 2 to 3 hours.

[0053] In another preferred embodiment, the stirring time in step 3 is 5 to 50 min, preferably 10 to 40 min, and more preferably 20 to 40 min.

[0054] In another preferred embodiment, the stirring is carried out under a vacuum degree of -0.1 MPa to -0.05 MPa, preferably -0.08 MPa to -0.05 MPa in step 4. In another preferred embodiment, the stirring time in step 4 is 30 to 100 min, preferably 40 to 90 min, and more preferably 50 to 80 min.

[0055] In another preferred embodiment, the stirring speeds in step 3 and step 4 are each independently 10 to 100 r / min, preferably 10 to 80 r / min, and more preferably 10 to 50 r / min.

[0056] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described below (such as embodiments) can be combined with each other to form a new or preferred technical solution. Due to space limitations, they will not be described one by one here. BRIEF DESCRIPTION OF THE DRAWINGS

[0057] Figure 1 This is the therapeutic effect of the diseased part of the mouse after one week of administration. DETAILED DESCRIPTION

[0058] After long-term and in-depth research, through a large number of screenings, the inventors have developed a selenium disulfide gel for the first time, which comprises selenium disulfide, a sunscreen and a gel matrix, and optionally an ion regulator, a moisturizer, a pH regulator and purified water. The selenium disulfide gel of the present invention uses materials with good biocompatibility, reduces skin irritation, improves patient compliance and safety, and the gel is easy to store, transport, and carry, which is more convenient. Based on this, the inventors have completed the present invention.

[0059] Selenium disulfide gel of the present invention

[0060] The invention provides a selenium disulfide gel, which comprises selenium disulfide, a sunscreen, an ion regulator, a gel matrix, a moisturizer, a pH regulator and purified water.

[0061] In some embodiments, the sunscreen is titanium dioxide.

[0062] In some embodiments, the ion modifier is sodium chloride.

[0063] In some embodiments, the gel matrix is ​​xanthan gum or carbomer; preferably xanthan gum.

[0064] In some embodiments, the humectant is glycerin.

[0065] In some embodiments, the pH adjusters are citric acid and sodium hydroxide.

[0066] In some embodiments, the gel comprises 1.0-2.0 parts by weight of selenium disulfide, 0.1-0.5 parts by weight of a sunscreen, 0-1.0 parts by weight of an ion regulator, 1.0-3.0 parts by weight of a gel base, and 2.0-10.0 parts by weight of a moisturizer.

[0067] In some embodiments, the gel comprises 1.0-2.0 parts by weight of the gel matrix.

[0068] In some embodiments, the gel comprises 5.0-10.0 parts by weight of a moisturizer.

[0069] In some embodiments, the selenium disulfide has a D 90 5.0-80.0 μm; preferably 4.0-7.0 μm.

[0070] In some embodiments, the pH range of the gel is 3.5-6.0; preferably 3.5-5.0.

[0071] Beneficial effects of the present invention

[0072] (1) The present invention provides a novel selenium disulfide preparation, which adopts materials with good biocompatibility, reduces skin irritation, improves patient compliance and safety, and provides a new administration method for the clinical application of selenium disulfide.

[0073] (2) The gel provided by the present invention is filled in an ointment tube, which is convenient for storage, transportation and carrying.

[0074] (3) The gel provided by the present invention has the characteristic of not being able to be absorbed through the skin and exerts its efficacy only locally on the skin, thereby avoiding side effects caused by local or systemic absorption of the drug and reducing side effects.

[0075] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only intended to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples without specifying specific conditions are usually implemented under conventional conditions or according to the conditions recommended by the manufacturer.

[0076] Unless otherwise defined herein, scientific and technical terms related to the present invention shall have the meanings understood by those of ordinary skill in the art.

[0077] Example 1

[0078] Weigh 1g of xanthan gum and dissolve it in 50g of purified water, add 0.5g of sodium chloride, and stir until dissolved. Weigh 1g of selenium disulfide and 0.5g of titanium dioxide and add them to the above xanthan gum, homogenize for 10min using a high-pressure homogenizer shearing machine at 10000r / min, add 5g of glycerol, and stir evenly. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-5.5, add purified water to 100g, and stir evenly. Selenium disulfide is easy to form lumps during storage. This example investigates the effect of high-pressure homogenization shearing on the distribution of selenium disulfide in the preparation.

[0079] The results showed that the high-pressure homogenization shearing method could make most of the selenium disulfide evenly dispersed in the preparation, but a small amount of large particles could not be dispersed. Therefore, it is necessary to pretreat the selenium disulfide using a suitable method before preparing the gel.

[0080] Example 2

[0081] Selenium disulfide was pretreated using a jet mill, with an upper air inlet pressure of 3 bar, a lower air inlet pressure of 2 bar, and a crushing time of about 30 minutes. The particle size of the crushed API was tested.

[0082] Table 1 Effect of air flow milling on selenium disulfide particle size and particle size distribution

[0083]

[0084] Note: Span is the particle size span, Span = (D 90 -D 10 ) / D 50 The smaller the Span value, the more uniform the particle size and the higher the size consistency.

[0085] The results showed that the particle size of the API was significantly reduced after airflow pulverization, and the uniformity was good. However, the color of the API changed from orange to brown after pulverization. Therefore, selenium disulfide is not suitable for this pulverization method.

[0086] Example 3

[0087] Selenium disulfide was pretreated by ball milling. Selenium disulfide was dispersed in purified water at a speed of 60 r / min. The weight ratio of ball milling balls to materials was 2:1. Samples were taken at 1 h, 3 h, 5 h, and 7 h after ball milling. The samples were centrifuged at 15000 r / min for 10 min in a high-speed centrifuge, and the solid particles in the lower layer were dried at 40 °C. The particle size of selenium disulfide at different ball milling times was detected by Malvern particle size laser instrument.

[0088] Table 2 Effect of ball milling time on particle size and particle size distribution of selenium disulfide

[0089]

[0090]

[0091] The results showed that when the ball milling time was ≥3h, the particle size of selenium disulfide was relatively uniform (D 90 4.0~7.0μm), indicating that ball milling time ≥3h can ensure that selenium disulfide can be fully dispersed, which is conducive to the uniform dispersion of selenium disulfide in the gel matrix.

[0092] Example 4

[0093] Weigh 1g of selenium disulfide and 0.1g of titanium dioxide and suspend them in 30g of purified water. Mill for 3h to obtain a ball-milling solution. Add the ball-milling solution to the xanthan gum matrix prepared in advance (1g of xanthan gum is dissolved in 50g of purified water), add 2g of glycerol, and stir for 2-3h until uniform. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-4.0, add purified water to 100g, and stir for ~1h until uniform. Fill the sample into an ointment tube and seal it, 15g / tube.

[0094] Example 5

[0095] Weigh 1g of selenium disulfide and 0.5g of titanium dioxide and suspend them in 30g of purified water. Mill for 3h to obtain a ball-milling solution. Add the ball-milling solution to the xanthan gum matrix prepared in advance (1g of xanthan gum dissolved in 50g of purified water), add 0.5g of sodium chloride and 5g of glycerol, and stir for 2-3h until uniform. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-4.0, add purified water to 100g, and stir for ~1h until uniform. Fill the sample into an ointment tube and seal it, 15g / tube.

[0096] Example 6

[0097] Weigh 1g of selenium disulfide and 0.25g of titanium dioxide and suspend them in 30g of purified water. Mill for 3h to obtain a ball-milling solution. Add the ball-milling solution to the xanthan gum matrix prepared in advance (1g of xanthan gum dissolved in 50g of purified water), add 1g of sodium chloride and 10g of glycerol, and stir for 2-3h until uniform. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-4.0, add purified water to 100g, and stir for ~1h until uniform. Fill the sample into an ointment tube and seal it, 15g / tube.

[0098] Example 7

[0099] Weigh 1g of selenium disulfide and 0.5g of titanium dioxide and suspend them in 30g of purified water. Mill for 3h to obtain a ball-milling solution. Add the ball-milling solution to the xanthan gum matrix prepared in advance (2g of xanthan gum dissolved in 50g of purified water), add 10g of glycerol, and stir for 2-3h until uniform. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-4.0, add purified water to 100g, and stir for ~1h until uniform. Fill the sample into an ointment tube and seal it, 15g / tube.

[0100] Example 8

[0101] Weigh 1g of selenium disulfide and 0.25g of titanium dioxide and suspend them in 30g of purified water. Mill for 3h to obtain a ball-milling solution. Add the ball-milling solution to the xanthan gum matrix prepared in advance (2g of xanthan gum dissolved in 50g of purified water), add 0.5g of sodium chloride and 2g of glycerol, and stir for 2-3h until uniform. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-4.0, add purified water to 100g, and stir for ~1h until uniform. Fill the sample into an ointment tube and seal it, 15g / tube.

[0102] Example 9

[0103] Weigh 1g of selenium disulfide and 0.1g of titanium dioxide and suspend them in 30g of purified water. Mill for 3h to obtain a ball-milling solution. Add the ball-milling solution to the xanthan gum matrix prepared in advance (2g of xanthan gum dissolved in 50g of purified water), add 1g of sodium chloride and 5g of glycerol, and stir for 2-3h until uniform. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-4.0, add purified water to 100g, and stir for ~1h until uniform. Fill the sample into an ointment tube and seal it, 15g / tube.

[0104] Example 10

[0105] Weigh 1g of selenium disulfide and 0.25g of titanium dioxide and suspend them in 30g of purified water. Mill for 3h to obtain a ball-milling solution. Add the ball-milling solution to the xanthan gum matrix prepared in advance (3g of xanthan gum dissolved in 50g of purified water), add 5g of glycerol, and stir for 2-3h until uniform. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-4.0, add purified water to 100g, and stir for ~1h until uniform. Fill the sample into an ointment tube and seal it, 15g / tube.

[0106] Embodiment 11

[0107] Weigh 1g of selenium disulfide and 0.1g of titanium dioxide and suspend them in 30g of purified water. Mill for 3h to obtain a ball-milling solution. Add the ball-milling solution to the xanthan gum matrix prepared in advance (3g of xanthan gum dissolved in 50g of purified water), add 0.5g of sodium chloride and 10g of glycerol, and stir for 2-3h until uniform. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-4.0, add purified water to 100g, and stir for ~1h until uniform. Fill the sample into an ointment tube and seal it, 15g / tube.

[0108] Example 12

[0109] Weigh 1g of selenium disulfide and 0.5g of titanium dioxide and suspend them in 30g of purified water. Mill for 3h to obtain a ball-milling solution. Add the ball-milling solution to the xanthan gum matrix prepared in advance (3g of xanthan gum dissolved in 50g of purified water), add 1g of sodium chloride and 2g of glycerol, and stir for 2-3h until uniform. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-4.0, add purified water to 100g, and stir for ~1h until uniform. Fill the sample into an ointment tube and seal it, 15g / tube.

[0110] Embodiment 13

[0111] The same as Example 5, except that citric acid and / or sodium hydroxide are used to adjust the pH to 4.0-5.0.

[0112] Embodiment 14

[0113] The same as Example 5, except that citric acid and / or sodium hydroxide are used to adjust the pH to 5.0-6.0.

[0114] The results show that selenium disulfide will gradually change color in an environment with a pH value greater than 5.0, so the pH value of the preparation of the present invention is preferably ≤5.

[0115] Embodiment 15

[0116] Examples 4 to 14 used a conventional stirring method, but during the preparation process, it was found that a small amount of bulk drug in the preparation could not be effectively dispersed in a short time, and a long stirring time was required, which was time-consuming. Therefore, based on the confirmed prescriptions of Examples 4 to 14, Example 15 optimized the process according to the phenomenon observed during the preparation process.

[0117] Weigh 1g of selenium disulfide and 0.5g of titanium dioxide and suspend them in 30g of purified water. Mill for 3h to obtain a ball milling solution. Add the ball milling solution to the xanthan gum matrix prepared in advance (1g of xanthan gum is dissolved in 50g of purified water), stir evenly, and then add 0.5g of sodium chloride. Use a high-pressure homogenizer for homogenization and dispersion, 10000r / min, homogenization for 15min. Add 5g of glycerol and stir slowly (~20rpm) for 30min at a vacuum degree of ≤-0.05MPa. Use citric acid and / or sodium hydroxide to adjust the pH to 3.5-5.0, add purified water to 100g, and continue to stir slowly for 60min at a vacuum degree of ≤-0.05MPa. Fill the sample into an ointment tube and seal it, 15g / tube.

[0118] The difference from other embodiments is that a homogenization method is used to shorten the stirring time before adding glycerol, and a reduced pressure degassing method is used to eliminate bubbles in the product.

[0119] Example 16

[0120] The same as Example 15, the only difference is that the amount of selenium disulfide in the prescription is 2g.

[0121] Embodiment 17

[0122] Weigh 1g of Carbomer 940 and add it to about 80g of purified water. Use a high-pressure homogenizer to homogenize and disperse until there are no obvious lumps. Heat to 50-60°C and stir until dissolved. Adjust the pH to 7.0 with triethanolamine and stir slowly to form a uniform gel matrix. Add 1g of selenium disulfide to the matrix and use a high-pressure homogenizer to homogenize and disperse at 10,000r / min for 5 minutes. Add 5g of glycerol and stir evenly. Use citric acid and / or triethanolamine to adjust the pH to 3.5-5.5, add water to the total prescription amount, and stir evenly.

[0123] The difference from other embodiments is that the gel matrix is ​​carbomer.

[0124] The results show that when carbomer is used as the gel matrix, the gel viscosity changes to varying degrees during the addition of selenium disulfide and pH adjustment. Therefore, the preparation of the present invention is not preferably carbomer as the gel matrix.

[0125] Test Example 1. Stability

[0126] The samples of Examples 4 to 12 of the present invention were placed at 40° C. or under 4500 lx±500 lx light for stability investigation, and samples were taken on day 0 and day 10 to detect properties, pH, viscosity, and particle size.

[0127] Properties: Visual method.

[0128] pH: Chinese Pharmacopoeia 2020 Edition, Part IV, General Rules 0631.

[0129] Viscosity: The viscosity was tested using a Brookfield DVNext viscometer with a rotor model of CP-51, a rotation speed of 5 rpm, a balancing time of 2 min, a test time of 2 min, a sample chamber temperature of 32 °C, and a sample load of approximately 0.5 g.

[0130] Particle size: Using the microscope method, take an appropriate amount of sample and smear it on a glass slide, cover it with a cover glass, and gently press to evenly distribute the particles, taking care to prevent bubbles from mixing in. Observe under a 50x microscope, there should be no obvious agglomeration phenomenon. Then randomly select 3 fields of view under a 200x microscope, use the system's own software to count the number and size of particles, and output a report.

[0131] The experimental results are shown in Table 3:

[0132] Table 3 Research results of different prescriptions

[0133]

[0134]

[0135] From the research results in Table 3, we can see that:

[0136] 1. The amount of xanthan gum in Examples 4 to 6 is 1% (w / w), the amount of xanthan gum in Examples 7 to 9 is 2% (w / w), and the amount of xanthan gum in Examples 10 to 12 is 3% (w / w). The results show that the viscosity of Examples 10 to 12 is greater than that of Examples 7 to 9 and greater than that of Examples 4 to 6, indicating that the amount of xanthan gum is positively correlated with the viscosity of the gelling agent.

[0137] When the amount of xanthan gum is 3% (w / w), the viscosity of the gel is relatively large (>5000), which is not conducive to coating, and the fluidity is poor, which is not conducive to filling; when the amount of xanthan gum is 1% to 2% (w / w), the viscosity is moderate (1000 to 4500) and the fluidity is good. Therefore, in the preparation of the present invention, the amount of xanthan gum is preferably 1% to 2% (w / w).

[0138] 2. Titanium dioxide is commonly used as a colorant, physical sunscreen, etc. The amount of titanium dioxide used in the formulation of the present invention is 0.1% to 0.5% (w / w). The results show that when the prepared sample is placed under 4500lx±500lx for 10 days, there is no obvious change in the appearance of the sample compared with 0 days, indicating that the preparation of the present invention can effectively prevent light exposure and is conducive to transportation and long-term storage.

[0139] 3. Glycerol is a humectant, wherein the amount of glycerol in Examples 4, 8 and 12 is 2% (w / w), the amount of glycerol in Examples 5 and 9 is 5% (w / w), and the amount of glycerol in Examples 6, 7, 10 and 11 is 10% (w / w). The experimental results show that after being placed under the influencing factors for 10 days, the viscosity of the preparations with a glycerol amount of 2% (Examples 4, 8 and 12) tends to decrease; the viscosity of the preparations with a glycerol amount of 5% and 10% (Examples 5 to 7 and 9 to 11) has no obvious decreasing trend.

[0140] 4. Variance analysis and F test were performed using viscosity as an indicator, which showed that the amount of sodium chloride had little effect on the viscosity of the product. If sodium chloride is needed to achieve thickening effect in the future, further increasing the concentration of sodium chloride may be considered.

[0141] In summary, among Examples 4 to 12 of the present invention, the prescription compositions of Examples 5 to 7 and 9 are preferred.

[0142] Test Example 2. Stability

[0143] The samples of Examples 5, 13, 14 and 15 of the present invention were placed at 40° C. for stability study, and samples were taken on day 0 and day 10 to detect properties, pH, viscosity, content and particle size.

[0144] The properties, pH, viscosity and particle size tests were the same as those in Test Example 1.

[0145] Content: Accurately weigh an appropriate amount (approximately equivalent to 0.1g of selenium disulfide) of gel, add 25ml of fuming nitric acid, heat in a water bath for 2 hours, cool, transfer to a 100ml volumetric flask, dilute to the scale with water, shake well, filter, accurately measure 20ml of the filtrate, add 10g of urea and 25ml of water, heat to boiling, cool, add 10ml of potassium iodide test solution and 3ml of starch indicator solution, immediately titrate with sodium thiosulfate titrant (0.05mol / L) until the solution changes from reddish brown to orange-red, and correct the titration result with a blank test.

[0146] The experimental results are shown in Table 4 below:

[0147] Table 4 pH range and homogenization method investigation results

[0148]

[0149] The results show that:

[0150] 1. After being placed at 40°C for 10 days, the properties, pH and viscosity of the preparations with a pH range of 3.5 to 5.0 (Examples 5, 13 and 15) were not significantly different from those at day 0; the color of the preparation with a pH>5.0 (Example 14) changed from orange-yellow to brown-yellow. Therefore, the preferred pH range of the preparation of the present invention is 3.5 to 5.0.

[0151] 2. Since the viscosity of the preparation of the present invention is relatively large, conventional stirring takes a long time, easily generates bubbles and is difficult to eliminate. The inventors use a homogenization method for dispersion, which can effectively shorten the stirring time. However, the homogenization dispersion speed is high, and bubbles are more likely to be generated and difficult to eliminate than conventional stirring. Therefore, a reduced pressure degassing method is used to eliminate bubbles in the product.

[0152] The test results of Example 15 are the same as those of other examples, indicating that homogenizing and dispersing with a high-pressure homogenizer and stirring under a vacuum degree of ≤-0.05 MPa have no significant effect on product quality.

[0153] In summary, among Examples 13 to 15 of the present invention, the prescription compositions of Examples 13 and 15 are preferred.

[0154] Test Example 3. In vitro transdermal effect

[0155] The in vitro transdermal test of selenium disulfide gel was conducted using a fully automatic dry heating transdermal system. The selenium disulfide gel used in the experiment was the preparation of Example 15, and the skin used was the back and abdomen skin of a 1-month-old male Bama miniature pig, with a thickness of about 0.8 mm to 1.0 mm.

[0156] The skin integrity test was performed by the resistance method before and after use to ensure the validity of the experimental results (the skin resistance value is 3 times or more of the background value, which is considered to be intact skin). The receiving medium is 0.9% sodium chloride solution, the receiving cell temperature is 32°C, the speed is 600rpm, the sampling time points are 1h, 2h, 4h, 6h, 12h, 24h, the sample amount is 200mg, and the diffusion cell volume is 12ml.

[0157] The experimental results are shown in Table 5:

[0158] Table 5 Selenium disulfide gel in vitro skin permeation test results

[0159] project Test results Cumulative transmittance 0.00％ Percentage of intradermal retention 0.92％±0.53％ Residue ratio 92.25％±2.00％ Mass recovery 93.17％±2.07％

[0160] The results showed that this product could not penetrate the skin and only a small amount was retained in the skin.

[0161] Test Example 4. Therapeutic effect on atopic dermatitis

[0162] The specific dermatitis model of ICR mice was constructed using 2,4-dinitrochlorobenzene to construct a specific dermatitis model, and the therapeutic effect of selenium disulfide gel on atopic dermatitis was preliminarily evaluated. Four groups were set up in this experiment, namely the normal control group, the negative control group (model group), the 1% selenium disulfide gel group (Example 15), and the 2% selenium disulfide gel group (Example 16). The normal group and the negative control group were given 0.9% sodium chloride solution on the affected area. Both the 1% selenium disulfide gel group and the 2% selenium disulfide gel group applied a thin layer of gel on the affected area once a day. The condition of the affected area of ​​the mouse was recorded daily to preliminarily judge the therapeutic effect of selenium disulfide gel on atopic dermatitis.

[0163] The test results are as follows Figure 1 As shown, the results showed that after 1 week of administration, compared with the model group, the inflammation of the mice treated with the 1% selenium sulfide gel group and the 2% selenium sulfide gel group was significantly improved, and the 1% treatment group was slightly better than the 2% treatment group. Some mice in the 2% treatment group had persistent skin damage and bleeding. Therefore, the preferred amount of selenium sulfide in this preparation is <2% (w / w).

[0164] The above descriptions are merely embodiments of the present invention and are not intended to limit the scope of the substantial technical content of the present invention. The substantial technical content of the present invention is broadly defined in the scope of the claims of the application. Any technical entity or method completed by others, if it is exactly the same as that defined in the scope of the claims of the application or is an equivalent variation, will be deemed to be included in the scope of the claims.

Claims

1. A selenium disulfide gel, characterized in that: The gel comprises selenium disulfide, a sunscreen, a gel base, a moisturizer, a pH adjuster and purified water; Wherein, the gel matrix is ​​selected from the group consisting of xanthan gum, carbomer, and sodium carboxymethyl cellulose; The mass ratio of selenium disulfide to the gel matrix is ​​1:(0.1-10).

2. The gelling agent according to claim 1, characterized in that The pH regulator is citric acid and / or sodium hydroxide.

3. The gelling agent according to claim 1, characterized in that The moisturizing agent is selected from the group consisting of glycerin, propylene glycol, and sodium hyaluronate.

4. The gelling agent according to claim 1, characterized in that The pH range of the gel is 2.0 to 5.0, preferably 3.0 to 5.0, and more preferably 3.5 to 5.

0.

5. The gelling agent according to claim 1, characterized in that: The gel further contains an ion regulator.

6. The gelling agent according to claim 5, characterized in that The ion regulator is selected from the following group: sodium chloride, sodium dihydrogen phosphate, and sodium citrate.

7. The gelling agent according to claim 1, characterized in that The gel comprises 1.0-2.0 parts by weight of selenium disulfide, 0.1-5.0 parts by weight of a sunscreen, 0.1-8.0 parts by weight of a gel base, 2-20 parts by weight of a moisturizer, and 80-98 parts by weight of a pH regulator and purified water.

8. The gelling agent according to claim 5, characterized in that: The gelling agent further comprises 0 to 5 parts by weight of an ion regulator.

9. A use of the gelling agent according to claim 1, characterized in that: Used for preparing medicines for preventing or treating atopic dermatitis.

10. A method for preparing a gel according to claim 5, characterized in that: The steps include: 1) suspending selenium disulfide and sunscreen in water and performing ball milling; 2) adding gel matrix and optional ion regulator, and stirring; 3) Add moisturizer and stir; 4) Add a pH adjuster to adjust the pH to 2.0-5.0, add purified water, and stir; 5) Fill into ointment tube and seal.

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