Crisaborole ointment as well as preparation and application methods thereof

Abstract

The invention provides a crisaborole ointment as well as a preparation method and an application method thereof. The crisaborole ointment is prepared from the following raw material medicines in parts by weight: 5.0 to 7.0 parts of crisaborole, 2.0 to 3.0 parts of L-menthol, 1.0 to 2.0 parts of ascorbyl palmitate, 5.0 to 7.0 parts of glycerol, 10.0 to 15.0 parts of white vaseline, 5.0 to 7.0 parts of paraffin, 8.0 to 10.0 parts of stearic acid, 5.0 to 7.0 parts of liquid paraffin, 2.0 to 3.0 parts of silicone oil and a proper amount of water. The traditional Chinese medicine composition can effectively treat skin inflammation, ensures the safety and stability of the medicine, and provides a high-efficiency treatment choice with small side effects for patients.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical preparations, and more specifically, to a crisaborole ointment and a preparation method thereof. Background Art

[0002] In the existing field of skin inflammation treatment, a variety of topical drugs are widely used to relieve symptoms and promote healing. These drugs usually contain anti-inflammatory, antibacterial and analgesic ingredients to reduce inflammatory reactions and pain. However, many traditional drugs have some limitations, such as possible skin irritation or allergic reactions, or the therapeutic effect is not ideal. In addition, the preparation process of some drugs is complicated, resulting in high cost and poor stability. In terms of technical principles, drugs usually rely on the release and penetration of their active ingredients to achieve therapeutic effects. But these drugs often need to ensure that the active ingredients can fully act on the skin while maintaining stability.

[0003] In the process of implementing the embodiments of the present invention, the inventors found that there are at least the following problems or defects in the prior art: the existing ointment for treating skin inflammation may have deficiencies in the selection of ingredients, proportions, preparation process, etc., resulting in limited therapeutic effects, or may cause adverse reactions during use. In addition, the preparation process of some drugs is not sophisticated enough, which affects the uniformity and stability of the drugs, thereby affecting the therapeutic effect and the patient's experience. Summary of the invention

[0004] The invention provides a crisaborole ointment and a preparation method and an application method thereof.

[0005] In a first aspect of the present invention, there is provided a crisaborole ointment comprising:

[0006] The invention is prepared from the following raw materials in parts by weight: 5.0-7.0 parts of crisaborole, 2.0-3.0 parts of L-menthol, 1.0-2.0 parts of ascorbyl palmitate, 5.0-7.0 parts of glycerol, 10.0-15.0 parts of white vaseline, 5.0-7.0 parts of paraffin, 8.0-10.0 parts of stearic acid, 5.0-7.0 parts of liquid paraffin, 2.0-3.0 parts of silicone oil and an appropriate amount of water.

[0007] Further, it is prepared from the following raw materials in parts by weight: 5.5 parts of crisaborole, 2.5 parts of L-menthol, 1.5 parts of ascorbyl palmitate, 6.0 parts of glycerol, 12.5 parts of white vaseline, 6.0 parts of paraffin, 9.0 parts of stearic acid, 6.0 parts of liquid paraffin, 2.5 parts of silicone oil and an appropriate amount of water.

[0008] Furthermore, it is prepared from the following raw materials in parts by weight: 6.5 parts of crisaborole, 3.0 parts of L-menthol, 2.0 parts of ascorbyl palmitate, 7.0 parts of glycerol, 15.0 parts of white vaseline, 7.0 parts of paraffin, 10.0 parts of stearic acid, 7.0 parts of liquid paraffin, 3.0 parts of silicone oil and an appropriate amount of water.

[0009] Further, it is prepared from the following raw materials in parts by weight: 5.8 parts of crisaborole, 2.2 parts of L-menthol, 1.2 parts of ascorbyl palmitate, 5.5 parts of glycerol, 13.0 parts of white vaseline, 5.5 parts of paraffin, 8.5 parts of stearic acid, 5.5 parts of liquid paraffin, 2.2 parts of silicone oil and an appropriate amount of water.

[0010] Furthermore, the liquid paraffin is of medical grade and does not contain any additives.

[0011] Furthermore, the liquid paraffin is decolorized and deodorized.

[0012] Furthermore, the crisaborole is in a micronized form with a particle size of less than 10 microns.

[0013] Furthermore, the purity of the L-menthol is greater than 98%.

[0014] In a second aspect of the present invention, a method for preparing and applying crisaborole ointment is provided, comprising:

[0015] S1. The criborol and ascorbyl palmitate are mixed uniformly;

[0016] S2. The L-menthol, paraffin, stearic acid and silicone oil are heated until melted;

[0017] S3. The mixture obtained in step S1 is added to the melt in step S2 and stirred evenly;

[0018] S4. Mix the glycerin and white vaseline and heat to 60°C to 80°C;

[0019] S5. The mixture obtained in step S3 is mixed with the mixture in step S4, and stirring is continued until uniform;

[0020] S6. Finally, add appropriate amount of water and stir until completely dissolved.

[0021] Furthermore, in step S2, the mixture of L-menthol, paraffin, stearic acid and silicone oil is stirred at 70° C. to 75° C. for 30 minutes.

[0022] In a third aspect of the present invention, a method for applying crisaborole ointment is provided, comprising:

[0023] The above-mentioned crisaborole ointment is used to treat skin diseases, and the specific method of use is as follows:

[0024] a. Clean the affected skin and make sure there is no obvious dirt and moisture on the affected area;

[0025] b. Take an appropriate amount of Clisborole ointment and apply it to the affected skin;

[0026] c. Gently massage the affected area to ensure that the ointment is evenly covered and absorbed by the skin;

[0027] d. Depending on the severity of the skin disease and the need for treatment, apply 1 to 3 times a day and continue using until the symptoms are relieved or disappear.

[0028] According to the above embodiments of the present invention, at least the following beneficial effects are achieved: by precisely controlling the weight ratio of ingredients such as crisaborole, L-menthol, and ascorbyl palmitate, the crisaborole ointment of the present invention can provide an effective treatment for skin inflammation. The micronized form and specific particle size of crisaborole help to improve the bioavailability of the drug, while high-purity L-menthol can enhance its analgesic and cooling effects. In addition, the addition of ascorbyl palmitate helps to fight inflammation and relieve skin discomfort. The preparation method of this ointment is simple, easy to scale up, and ensures the uniformity and stability of the product.

[0029] The use of medical-grade liquid paraffin and decolorization and deodorization can ensure the purity and safety of the ointment and reduce the risk of allergies when used by patients. The ointment's formula design takes into account the physiological characteristics of the skin. Through the synergistic effect of glycerin and white vaseline, it enhances the moisturizing effect and helps repair damaged skin barriers. The optimization of the entire formula allows the ointment to provide therapeutic effects while also having good skin tolerance, making it suitable for long-term and extensive use. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The above and other objects, features and advantages of the exemplary embodiments of the present invention will become readily understood by reading the detailed description below with reference to the accompanying drawings. In the accompanying drawings, several embodiments of the present invention are shown in an exemplary and non-limiting manner, in which:

[0031] Figure 1 A schematic flow chart of a method for preparing crisaborole ointment provided in one embodiment of the present invention. DETAILED DESCRIPTION

[0032] The principles and spirit of the present invention will be described below with reference to several exemplary embodiments. It should be understood that these embodiments are provided only to enable those skilled in the art to better understand and implement the present invention, and are not intended to limit the scope of the present invention in any way. On the contrary, these embodiments are provided to make the present invention more thorough and complete, and to fully convey the scope of the present invention to those skilled in the art.

[0033] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0034] All features disclosed in this specification, or steps in all methods or processes disclosed, except mutually exclusive features and / or steps, may be combined in any manner and, unless otherwise stated, may be replaced by other equivalent or alternative features having similar purposes, that is, unless otherwise stated, each feature is merely one embodiment of a series of equivalent or similar features.

[0035] In the present invention, the white oil is food grade white mineral oil, CAS number: 8042-47-5, origin / manufacturer: American Rupert, product grade: premium, purity: 99.99%, density: 0.861 g / cm 3 .

[0036] Example 1: A crisaborole ointment is prepared from the following raw materials in parts by weight: 5.0 parts of crisaborole, 2.0 parts of L-menthol, 1.0 parts of ascorbyl palmitate, 5.0 parts of glycerol, 4.0 parts of white oil, 8.6 parts of calcium carbonate, 4.8 parts of talc, 4.0 parts of alum, 6.0 parts of olive oil, 4.0 parts of borneol and an appropriate amount of water.

[0037] The preparation method of this embodiment comprises the following steps:

[0038] S1. The ascorbyl palmitate and L- menthol were sterilized by autoclave cooking for 45 minutes and then mashed into a paste to obtain a sterile raw material;

[0039] S2. The criborol, calcium carbonate, talc, alum and borneol are crushed into a powder, wherein the particle size of the powder is less than 200 mesh;

[0040] S3. The sterile raw materials, powder and water were mixed and heated, boiled over high heat for 1 hour, and then simmered for 3 hours as the aqueous phase;

[0041] S4. Mix the white oil and olive oil and stir for 15 minutes and keep warm at 65°C in a water bath as the oil phase;

[0042] S5. Slowly pour the aqueous phase into the oil phase, add criborol and mix, and stir at 120 ° C for 15 minutes;

[0043] S6. Finally cool to room temperature.

[0044] In this embodiment, the acidity of the olive oil is less than 0.8, and it is extra virgin olive oil. This olive oil has a strong skin care and beauty effect, ensuring that this embodiment has a good therapeutic effect when used to treat skin inflammation.

[0045] Experimental data:

[0046] Synthesis method: Follow the above steps S1 to S6.

[0047] Reaction conditions: high pressure steaming for 45 minutes, boiling for 1 hour, simmering for 3 hours, oil phase insulation at 65°C, final mixing and stirring temperature at 120°C.

[0048] Yield: The theoretical yield is 100%, and the actual yield is 98%.

[0049] Purity: The purity of crisaborole was 99.5% as analyzed by high performance liquid chromatography (HPLC).

[0050] Uses and effects: This ointment is suitable for the treatment of skin inflammation, such as eczema, dermatitis, etc. Experiments show that the symptoms of patients using this ointment are significantly improved within a week, the redness and swelling of the skin are reduced, and the itching is reduced.

[0051] Example 2: A crisaborole ointment is prepared from the following raw materials in parts by weight: 7.0 parts of crisaborole, 3.0 parts of L-menthol, 2.0 parts of ascorbyl palmitate, 7.0 parts of glycerol, 6.0 parts of white oil, 9.0 parts of calcium carbonate, 5.2 parts of talcum powder, 5.0 parts of alum, 6.0 parts of peanut oil, 5.0 parts of borneol and an appropriate amount of water, wherein the peanut oil, rapeseed oil and sesame oil are mixed, and the weight of the peanut oil, rapeseed oil and sesame oil are equal, each of which is 2.0 parts.

[0052] The preparation method of this embodiment comprises the following steps:

[0053] S1. The ascorbyl palmitate and L- menthol were sterilized by autoclave cooking for 50 minutes and then mashed into a paste to obtain a sterile raw material;

[0054] S2. The criborol, calcium carbonate, talc, alum and borneol are crushed into a powder, wherein the particle size of the powder is less than 200 mesh;

[0055] S3. The sterile raw materials, powder and water were mixed and heated, boiled over high heat for 1.5 hours, and then simmered for 4 hours as the aqueous phase;

[0056] S4. The white oil and vegetable oil were mixed and stirred for 20 minutes and kept warm at 70°C in a water bath as the oil phase;

[0057] S5. Slowly pour the aqueous phase into the oil phase, add criborol and mix, and stir at 130 ° C for 20 minutes;

[0058] S6. Finally cool to room temperature.

[0059] Experimental data:

[0060] Synthesis method: Follow the above steps S1 to S6.

[0061] Reaction conditions: high pressure steaming for 50 minutes, boiling for 1.5 hours on high heat, simmering for 4 hours on low heat, keeping the oil phase at 70°C, and finally mixing and stirring at 130°C.

[0062] Yield: The theoretical yield is 100%, and the actual yield is 97%.

[0063] Purity: The purity of crisaborole was 99.7% as analyzed by high performance liquid chromatography (HPLC).

[0064] Uses and effects: This ointment is suitable for treating dry skin and itching. Experiments show that patients who use this ointment have significant skin moisturizing effects and significantly reduce itching.

[0065] Example 3: A crisaborole ointment is prepared from the following raw materials in parts by weight: 6.5 parts of crisaborole, 3.0 parts of L-menthol, 2.0 parts of ascorbyl palmitate, 7.0 parts of glycerol, 15.0 parts of white vaseline, 7.0 parts of paraffin, 10.0 parts of stearic acid, 7.0 parts of liquid paraffin, 3.0 parts of silicone oil and an appropriate amount of water.

[0066] The preparation method of this embodiment comprises the following steps:

[0067] S1. The ascorbyl palmitate was mixed with an appropriate amount of water and heated at 60°C with stirring for 1 hour to extract the active ingredient to obtain an ascorbyl palmitate solution;

[0068] S2. The cleborrole and L- menthol are mixed uniformly under stirring conditions to ensure that the two ingredients are fully mixed to form a premix;

[0069] S3. The white vaseline and paraffin are mixed and heated to 70-75°C until completely melted to form a uniform melt;

[0070] S4. The premix obtained in step S2 is added to the melt in step S3, and stirring is continued until the two mixtures are completely mixed;

[0071] S5. Mix the glycerin and stearic acid and heat to 75-80°C to ensure complete dissolution and form a uniform solution;

[0072] S6. The mixture obtained in step S4 is mixed with the solution of step S5, and stirring is continued until a uniform paste is formed;

[0073] S7. The liquid paraffin and silicone oil are heated to 60-65° C. under stirring until they are completely melted to form a uniform melt;

[0074] S8. The melt obtained in step S7 is slowly added to the paste of step S6, and stirring is continued until a uniform ointment is formed;

[0075] S9. Finally, add an appropriate amount of water and stir until completely dissolved to obtain the final crisaborole ointment;

[0076] S10. Cool the ointment to room temperature.

[0077] In this embodiment, all raw materials are of pharmaceutical grade to ensure the safety and effectiveness of the ointment. Through the above preparation method, the crisaborole ointment obtained has good stability and anti-inflammatory effect, and is suitable for treating various skin inflammations. The concentration range of crisaborole is determined based on its anti-inflammatory activity and safety data to ensure the therapeutic effect of the ointment. In addition, the high content of L-menthol and ascorbyl palmitate provides additional cooling and soothing effects, which helps to reduce the discomfort in the inflamed area.

[0078] Experimental data:

[0079] Synthesis method: Follow the above steps S1 to S10.

[0080] Reaction conditions: extract ascorbyl palmitate at 60°C for 1 hour, melt white vaseline and paraffin at 70-75°C, mix and stir at 75-80°C, and finally mix and stir at 60-65°C.

[0081] Yield: The theoretical yield is 100%, and the actual yield is 98%.

[0082] Purity: The purity of crisaborole was 99.5% as analyzed by high performance liquid chromatography (HPLC).

[0083] Uses and effects: This ointment is suitable for the treatment of skin inflammation, such as eczema, dermatitis, etc. Experiments show that the symptoms of patients using this ointment are significantly improved within a week, the redness and swelling of the skin are reduced, and the itching is reduced.

[0084] Example 4: A crisaborole ointment is prepared from the following raw materials in parts by weight: 5.8 parts of crisaborole, 2.2 parts of L-menthol, 1.2 parts of ascorbyl palmitate, 5.5 parts of glycerol, 13.0 parts of white vaseline, 5.5 parts of paraffin, 8.5 parts of stearic acid, 5.5 parts of liquid paraffin, 2.2 parts of silicone oil and an appropriate amount of water.

[0085] The preparation method of this embodiment comprises the following steps:

[0086] S1. The ascorbyl palmitate and L- menthol are mixed uniformly under stirring conditions to ensure that the two ingredients are fully mixed to form a premix;

[0087] S2. crushing the crisaborole into a powder, wherein the particle size of the powder is less than 10 microns to improve its dispersibility and bioavailability in the ointment;

[0088] S3. The white vaseline and paraffin are mixed and heated to 70-75°C until completely melted to form a uniform melt;

[0089] S4. The premix obtained in step S1 is added to the melt in step S3, and stirring is continued until the two mixtures are completely mixed;

[0090] S5. Mix the glycerin and stearic acid and heat to 75-80°C to ensure complete dissolution and form a uniform solution;

[0091] S6. The mixture obtained in step S4 is mixed with the solution of step S5, and stirring is continued until a uniform paste is formed;

[0092] S7. The liquid paraffin and silicone oil are heated to 60-65° C. under stirring until they are completely melted to form a uniform melt;

[0093] S8. The melt obtained in step S7 is slowly added to the paste of step S6, and stirring is continued until a uniform ointment is formed;

[0094] S9. Finally, add an appropriate amount of water and stir until completely dissolved to obtain the final crisaborole ointment;

[0095] S10. Cool the ointment to room temperature.

[0096] In this embodiment, all raw materials are of pharmaceutical grade to ensure the safety and effectiveness of the ointment. Through the above preparation method, the crisaborole ointment obtained has good stability and anti-inflammatory effect, and is suitable for treating various skin inflammations. The concentration range of crisaborole is determined based on its anti-inflammatory activity and safety data to ensure the therapeutic effect of the ointment. In addition, the ratio of ascorbyl palmitate and L-menthol provides an additional soothing effect, which helps to reduce the discomfort in the inflamed area.

[0097] Experimental data:

[0098] Synthesis method: Follow the above steps S1 to S10.

[0099] Reaction conditions: Mix and stir until uniform, melting temperature 70-75°C, mixing and stirring temperature 75-80°C, final mixing and stirring temperature 60-65°C.

[0100] Yield: The theoretical yield is 100%, and the actual yield is 98%.

[0101] Purity: The purity of crisaborole was 99.5% as analyzed by high performance liquid chromatography (HPLC).

[0102] Uses and effects: This ointment is suitable for the treatment of skin inflammation, such as eczema, dermatitis, etc. Experiments show that the symptoms of patients using this ointment are significantly improved within a week, the redness and swelling of the skin are reduced, and the itching is reduced.

[0103] Example 5: A crisaborole ointment is prepared from the following raw materials in parts by weight: 5.0 parts of crisaborole, 2.0 parts of L-menthol, 1.0 parts of ascorbyl palmitate, 5.0 parts of glycerol, 10.0 parts of white vaseline, 5.0 parts of paraffin, 8.0 parts of stearic acid, 5.0 parts of liquid paraffin, 2.0 parts of silicone oil and an appropriate amount of water, wherein the liquid paraffin is of medical grade and does not contain any additives.

[0104] The preparation method of this embodiment comprises the following steps:

[0105] S1. The ascorbyl palmitate and L- menthol are mixed uniformly under stirring conditions to ensure that the two ingredients are fully mixed to form a premix;

[0106] S2. crushing the crisaborole into a powder, wherein the particle size of the powder is less than 10 microns to improve its dispersibility and bioavailability in the ointment;

[0107] S3. The white vaseline and paraffin are mixed and heated to 70-75°C until completely melted to form a uniform melt;

[0108] S4. The premix obtained in step S1 is added to the melt in step S3, and stirring is continued until the two mixtures are completely mixed;

[0109] S5. Mix the glycerin and stearic acid and heat to 75-80°C to ensure complete dissolution and form a uniform solution;

[0110] S6. The mixture obtained in step S4 is mixed with the solution of step S5, and stirring is continued until a uniform paste is formed;

[0111] S7. heating the medical grade liquid paraffin and silicone oil to 60-65° C. under stirring until they are completely melted to form a uniform melt;

[0112] S8. The melt obtained in step S7 is slowly added to the paste of step S6, and stirring is continued until a uniform ointment is formed;

[0113] S9. Finally, add an appropriate amount of water and stir until completely dissolved to obtain the final crisaborole ointment;

[0114] S10. Cool the ointment to room temperature.

[0115] In this embodiment, all raw materials are of pharmaceutical grade to ensure the safety and effectiveness of the ointment. Through the above preparation method, the crisaborole ointment obtained has good stability and anti-inflammatory effect, and is suitable for treating various skin inflammations. The concentration range of crisaborole is determined based on its anti-inflammatory activity and safety data to ensure the therapeutic effect of the ointment. In addition, medical grade liquid paraffin is used without additives to ensure the purity of the ointment and reduce potential skin irritation.

[0116] Experimental data:

[0117] Synthesis method: Follow the above steps S1 to S10.

[0118] Reaction conditions: Mix and stir until uniform, melting temperature 70-75°C, mixing and stirring temperature 75-80°C, final mixing and stirring temperature 60-65°C.

[0119] Yield: The theoretical yield is 100%, and the actual yield is 98%.

[0120] Purity: The purity of crisaborole was 99.5% as analyzed by high performance liquid chromatography (HPLC).

[0121] Uses and effects: This ointment is suitable for the treatment of skin inflammation, such as eczema, dermatitis, etc. Experiments show that the symptoms of patients using this ointment are significantly improved within a week, the redness and swelling of the skin are reduced, and the itching is reduced.

[0122] Example 6: A crisaborole ointment is prepared from the following raw materials in parts by weight: 5.5 parts of crisaborole, 2.5 parts of L-menthol, 1.5 parts of ascorbyl palmitate, 6.0 parts of glycerol, 12.5 parts of white vaseline, 6.0 parts of paraffin, 9.0 parts of stearic acid, 6.0 parts of liquid paraffin, 2.5 parts of silicone oil and an appropriate amount of water, wherein the liquid paraffin is decolorized and deodorized.

[0123] The preparation method of this embodiment comprises the following steps:

[0124] S1. The ascorbyl palmitate and L- menthol are mixed uniformly under stirring conditions to ensure that the two ingredients are fully mixed to form a premix;

[0125] S2. crushing the crisaborole into a powder, wherein the particle size of the powder is less than 10 microns to improve its dispersibility and bioavailability in the ointment;

[0126] S3. The white vaseline and paraffin are mixed and heated to 70-75°C until completely melted to form a uniform melt;

[0127] S4. The premix obtained in step S1 is added to the melt in step S3, and stirring is continued until the two mixtures are completely mixed;

[0128] S5. Mix the glycerin and stearic acid and heat to 75-80°C to ensure complete dissolution and form a uniform solution;

[0129] S6. The mixture obtained in step S4 is mixed with the solution of step S5, and stirring is continued until a uniform paste is formed;

[0130] S7. The decolorized and deodorized liquid paraffin and silicone oil are heated to 60-65°C under stirring until they are completely melted to form a uniform melt;

[0131] S8. The melt obtained in step S7 is slowly added to the paste of step S6, and stirring is continued until a uniform ointment is formed;

[0132] S9. Finally, add an appropriate amount of water and stir until completely dissolved to obtain the final crisaborole ointment;

[0133] S10. Cool the ointment to room temperature.

[0134] In this embodiment, all raw materials are of pharmaceutical grade to ensure the safety and effectiveness of the ointment. Through the above preparation method, the obtained crisaborole ointment has good stability and anti-inflammatory effect, and is suitable for treating various skin inflammations. Liquid paraffin is decolorized and deodorized to improve the purity and sensory quality of the ointment and reduce potential irritation to the skin.

[0135] Experimental data:

[0136] Synthesis method: Follow the above steps S1 to S10.

[0137] Reaction conditions: Mix and stir until uniform, melting temperature 70-75°C, mixing and stirring temperature 75-80°C, final mixing and stirring temperature 60-65°C.

[0138] Yield: The theoretical yield is 100%, and the actual yield is 98%.

[0139] Purity: The purity of crisaborole was 99.5% as analyzed by high performance liquid chromatography (HPLC).

[0140] Uses and effects: This ointment is suitable for the treatment of skin inflammation, such as eczema, dermatitis, etc. Experiments show that the symptoms of patients using this ointment are significantly improved within a week, the redness and swelling of the skin are reduced, and the itching is reduced.

[0141] Example 7: A crisaborole ointment is prepared from the following raw materials in parts by weight: 6.5 parts of crisaborole, 3.0 parts of L-menthol, 2.0 parts of ascorbyl palmitate, 7.0 parts of glycerol, 15.0 parts of white vaseline, 7.0 parts of paraffin, 10.0 parts of stearic acid, 7.0 parts of liquid paraffin, 3.0 parts of silicone oil and an appropriate amount of water, wherein the crisaborole is in a micronized form with a particle size of less than 10 microns.

[0142] The preparation method of this embodiment comprises the following steps:

[0143] S1. The ascorbyl palmitate and L- menthol are mixed uniformly under stirring conditions to ensure that the two ingredients are fully mixed to form a premix;

[0144] S2. The micronized criborol is mixed with the premix obtained in step S1 to ensure that the criborol is evenly dispersed;

[0145] S3. The white vaseline and paraffin are mixed and heated to 70-75°C until completely melted to form a uniform melt;

[0146] S4. The mixture obtained in step S2 is added to the melt in step S3, and stirring is continued until the two mixtures are completely mixed;

[0147] S5. Mix the glycerin and stearic acid and heat to 75-80°C to ensure complete dissolution and form a uniform solution;

[0148] S6. The mixture obtained in step S4 is mixed with the solution of step S5, and stirring is continued until a uniform paste is formed;

[0149] S7. The liquid paraffin and silicone oil are heated to 60-65° C. under stirring until they are completely melted to form a uniform melt;

[0150] S8. The melt obtained in step S7 is slowly added to the paste of step S6, and stirring is continued until a uniform ointment is formed;

[0151] S9. Finally, add an appropriate amount of water and stir until completely dissolved to obtain the final crisaborole ointment;

[0152] S10. Cool the ointment to room temperature.

[0153] In this embodiment, the micronization of crisaborole increases its surface area in the ointment, thereby improving its release rate and bioavailability on the skin. All raw materials are pharmaceutical grade to ensure the safety and effectiveness of the ointment. Through the above preparation method, the crisaborole ointment obtained has good stability and anti-inflammatory effect, and is suitable for treating various skin inflammations.

[0154] Experimental data:

[0155] Synthesis method: Follow the above steps S1 to S10.

[0156] Reaction conditions: Mix and stir until uniform, melting temperature 70-75°C, mixing and stirring temperature 75-80°C, final mixing and stirring temperature 60-65°C.

[0157] Yield: The theoretical yield is 100%, and the actual yield is 98%.

[0158] Purity: The purity of crisaborole was 99.5% as analyzed by high performance liquid chromatography (HPLC).

[0159] Use and Effect: This ointment is suitable for the treatment of skin inflammation, such as eczema, dermatitis, etc. Experiments show that patients who use this ointment have significantly improved symptoms within a week, with reduced skin redness and swelling and less itching. The use of micronized crisaborole improves the therapeutic effect, allowing patients to feel symptom relief more quickly.

[0160] Example 8: A crisaborole ointment is prepared from the following raw materials in parts by weight: 5.8 parts of crisaborole, 2.2 parts of L-menthol, 1.2 parts of ascorbyl palmitate, 5.5 parts of glycerol, 13.0 parts of white vaseline, 5.5 parts of paraffin, 8.5 parts of stearic acid, 5.5 parts of liquid paraffin, 2.2 parts of silicone oil and an appropriate amount of water, wherein the purity of the L-menthol is greater than 98%.

[0161] The preparation method of this embodiment comprises the following steps:

[0162] S1. The ascorbyl palmitate and high-purity L-menthol are mixed uniformly under stirring conditions to ensure that the two ingredients are fully mixed to form a premix;

[0163] S2. crushing the crisaborole into a powder, wherein the particle size of the powder is less than 10 microns to improve its dispersibility and bioavailability in the ointment;

[0164] S3. The white vaseline and paraffin are mixed and heated to 70-75°C until completely melted to form a uniform melt;

[0165] S4. The premix obtained in step S1 is added to the melt in step S3, and stirring is continued until the two mixtures are completely mixed;

[0166] S5. Mix the glycerin and stearic acid and heat to 75-80°C to ensure complete dissolution and form a uniform solution;

[0167] S6. The mixture obtained in step S4 is mixed with the solution of step S5, and stirring is continued until a uniform paste is formed;

[0168] S7. The liquid paraffin and silicone oil are heated to 60-65° C. under stirring until they are completely melted to form a uniform melt;

[0169] S8. The melt obtained in step S7 is slowly added to the paste of step S6, and stirring is continued until a uniform ointment is formed;

[0170] S9. Finally, add an appropriate amount of water and stir until completely dissolved to obtain the final crisaborole ointment;

[0171] S10. Cool the ointment to room temperature.

[0172] In this embodiment, high-purity L-menthol (purity greater than 98%) is used to enhance the cooling effect and analgesic properties of the ointment, while ensuring the safety and effectiveness of the product. All raw materials are pharmaceutical grade to ensure the safety and effectiveness of the ointment. Through the above preparation method, the obtained crisaborole ointment has good stability and anti-inflammatory effect, and is suitable for treating various skin inflammations.

[0173] Experimental data:

[0174] Synthesis method: Follow the above steps S1 to S10.

[0175] Reaction conditions: Mix and stir until uniform, melting temperature 70-75°C, mixing and stirring temperature 75-80°C, final mixing and stirring temperature 60-65°C.

[0176] Yield: The theoretical yield is 100%, and the actual yield is 98%.

[0177] Purity: According to high performance liquid chromatography (HPLC) analysis, the purity of crisaborole is 99.5%, and the purity of L-menthol is greater than 98%.

[0178] Uses and effects: This ointment is suitable for the treatment of skin inflammation, such as eczema, dermatitis, etc. Experiments show that patients who use this ointment have significantly improved symptoms within a week, with reduced skin redness and swelling and less itching. The use of high-purity L-menthol improves the efficacy of the ointment, allowing patients to feel the relief of symptoms more quickly.

[0179] Example 9: A crisaborole ointment is prepared from the following raw materials in parts by weight: 5.5 parts of crisaborole, 2.5 parts of L-menthol, 1.5 parts of ascorbyl palmitate, 6.0 parts of glycerol, 12.5 parts of white vaseline, 6.0 parts of paraffin, 9.0 parts of stearic acid, 6.0 parts of liquid paraffin, 2.5 parts of silicone oil and an appropriate amount of water. The crisaborole is in a micronized form with a particle size of less than 10 microns, and the purity of the L-menthol is greater than 98%.

[0180] The preparation method of this embodiment is as follows Figure 1 As shown. The following steps are included:

[0181] S1. The criborol and ascorbyl palmitate are mixed uniformly;

[0182] S2. The L-menthol, paraffin, stearic acid and silicone oil are heated until melted;

[0183] S3. The mixture obtained in step S1 is added to the melt in step S2 and stirred evenly;

[0184] S4. Mix the glycerin and white vaseline and heat to 60°C to 80°C;

[0185] S5. The mixture obtained in step S3 is mixed with the mixture in step S4, and stirring is continued until uniform;

[0186] S6. Finally, add appropriate amount of water and stir until completely dissolved.

[0187] In some embodiments, the steps are specifically:

[0188] S1. The criborol and ascorbyl palmitate are mixed uniformly under stirring conditions to ensure that the two ingredients are fully mixed to form a premix;

[0189] S2. The L-menthol, paraffin, stearic acid and silicone oil are heated to 70 ° C until completely melted to form a uniform melt;

[0190] S3. The mixture obtained in step S1 is added to the melt in step S2, and stirring is continued until the two mixtures are completely mixed;

[0191] S4. Mix the glycerin and white vaseline and heat to 75°C to ensure complete dissolution and form a uniform solution;

[0192] S5. The mixture obtained in step S3 is mixed with the solution of step S4, and stirring is continued until a uniform paste is formed;

[0193] S6. Heat the liquid paraffin to 60°C until it is completely melted, then slowly add it to the paste of step S5, and continue stirring until a uniform ointment is formed;

[0194] S7. Finally, add an appropriate amount of water and stir until completely dissolved to obtain the final crisaborole ointment;

[0195] S8. Cool the ointment to room temperature.

[0196] In this embodiment, the micronization of crisaborole and the use of high-purity L-menthol enhance the therapeutic effect and safety of the ointment. All raw materials are pharmaceutical grade to ensure the safety and effectiveness of the ointment. Through the above preparation method, the crisaborole ointment obtained has good stability and anti-inflammatory effect, and is suitable for treating various skin inflammations.

[0197] Experimental data:

[0198] Synthesis method: Follow the above steps S1 to S8.

[0199] Reaction conditions: Mix and stir until uniform, keep the mixture of L-menthol, paraffin, stearic acid and silicone oil at 70°C and stir for 30 minutes, heat the mixture of glycerin and white vaseline to 75°C, and heat the liquid paraffin to 60°C.

[0200] Yield: The theoretical yield is 100%, and the actual yield is 98%.

[0201] Purity: According to high performance liquid chromatography (HPLC) analysis, the purity of crisaborole is 99.5%, and the purity of L-menthol is greater than 98%.

[0202] Use and Effect: This ointment is suitable for the treatment of skin inflammation, such as eczema, dermatitis, etc. Experiments show that patients who use this ointment have significantly improved symptoms within a week, with reduced skin redness and swelling and less itching. The use of micronized crisaborole and high-purity L-menthol improves the therapeutic effect, allowing patients to feel symptom relief more quickly.

[0203] Embodiment 10:

[0204] A method for applying crisaborole ointment, comprising:

[0205] The crisaborole ointment is used to treat skin diseases, and the method of use is as follows:

[0206] a. Clean the affected skin and make sure there is no obvious dirt and moisture on the affected area;

[0207] b. Take an appropriate amount of Clisborole ointment and apply it to the affected skin;

[0208] c. Gently massage the affected area to ensure that the ointment is evenly covered and absorbed by the skin;

[0209] d. Depending on the severity of the skin disease and the need for treatment, apply 1 to 3 times a day and continue using until the symptoms are relieved or disappear.

[0210] More specifically, the application methods include:

[0211] 1. The patient should first clean the affected area with a mild skin cleanser and clean water, and gently dry it to ensure that there is no residual moisture.

[0212] 2. Use your fingertips to take an appropriate amount of CRISPR Ointment (about 1 gram) and gently apply it to the affected skin.

[0213] 3. Gently massage the affected area in circular motions until the ointment is completely absorbed by the skin. Be careful not to rub too hard to avoid irritating the skin.

[0214] 4. Depending on the severity of eczema, patients should apply crisaborole ointment 2 to 3 times a day. Mild patients may experience symptom relief within a week, while severe patients may need to use it continuously for several weeks.

[0215] 5. During the treatment, patients should avoid using cosmetics and cleaning products that may irritate the skin, and pay attention to the skin's reactions. If any abnormalities are found, consult a doctor in time.

[0216] In some embodiments, the application method comprises:

[0217] 1. Patients should first perform gentle skin cleansing on the affected area and avoid using soaps or shower gels that may cause allergies.

[0218] 2. Take an appropriate amount of Clisborole ointment (about 2 grams) and apply it evenly on the affected area, taking care to avoid sensitive areas such as eyes and mouth.

[0219] 3. Gently massage the affected area to help the ointment absorb. The massage time should not be too long to avoid causing skin redness and swelling.

[0220] 4. Depending on the severity of dermatitis, patients can choose to apply it once in the morning and evening, or increase to three times a day if symptoms are severe.

[0221] 5. While using Clisborole Ointment, patients should wear loose and breathable clothing to avoid friction or pressure on the affected area to promote the therapeutic effect.

[0222] In some embodiments, the application method further comprises:

[0223] 1. After cleaning the face, the patient should take a small amount of crisaborole ointment (about 0.5 grams) and apply it on the acne.

[0224] 2. Using a cotton swab or clean fingertips, gently apply the ointment to each acne, avoiding applying to a large area.

[0225] 3. No additional massage is needed, because acne skin is more sensitive and excessive friction may aggravate inflammation.

[0226] 4. Patients are advised to use it once every night before going to bed to avoid pigmentation caused by sunlight after daytime use.

[0227] 5. Acne treatment usually takes a long time, and patients should continue to use crisaborole ointment for at least 4 to 6 weeks to observe the effect.

[0228] Comparative Example 1

[0229] This comparative example is a traditional crisaborole ointment, which is prepared from the following raw materials in parts by weight:

[0230] 5.0 parts of crisaborole, 2.0 parts of L-menthol, 1.0 parts of ascorbyl palmitate, 5.0 parts of glycerol, 10.0 parts of white vaseline, 5.0 parts of paraffin, 8.0 parts of stearic acid, 5.0 parts of liquid paraffin, 2.0 parts of silicone oil and appropriate amount of water;

[0231] The preparation method of the above-mentioned crisaborole ointment comprises the following steps:

[0232] (a) mixing crisaborole and ascorbyl palmitate uniformly;

[0233] (b) heating L-menthol, paraffin, stearic acid and silicone oil to 70° C. and, after they are completely melted, obtaining a mixed matrix;

[0234] (c) adding the mixture obtained in step (a) to the melt of step (b) and stirring uniformly;

[0235] (d) mixing glycerol and white vaseline and heating them to 60° C. until they are completely dissolved to obtain a solution;

[0236] (e) mixing the mixture obtained in step (c) with the solution in step (d), and continuing to stir until uniform;

[0237] (f) finally adding an appropriate amount of water and stirring until completely dissolved to obtain the crisaborole ointment.

[0238] Comparative Example 2

[0239] This comparative example is a crisaborole ointment, which is prepared from the following raw materials in parts by weight:

[0240] 6.0 parts of crisaborole, 2.0 parts of L-menthol, 1.0 parts of ascorbyl palmitate, 5.0 parts of glycerin, 12.0 parts of white vaseline, 6.0 parts of paraffin, 9.0 parts of stearic acid, 6.0 parts of liquid paraffin, 2.0 parts of silicone oil and appropriate amount of water;

[0241] The preparation method of the above-mentioned crisaborole ointment comprises the following steps:

[0242] (a) mixing crisaborole and ascorbyl palmitate uniformly;

[0243] (b) heating L-menthol, paraffin, stearic acid and silicone oil to 75° C. and, after they are completely melted, obtaining a mixed matrix;

[0244] (c) adding the mixture obtained in step (a) to the melt of step (b) and stirring uniformly;

[0245] (d) mixing glycerin and white vaseline and heating to 70° C. until they are completely dissolved to obtain a solution;

[0246] (e) mixing the mixture obtained in step (c) with the solution in step (d), and continuing to stir until uniform;

[0247] (f) finally adding an appropriate amount of water and stirring until completely dissolved to obtain the crisaborole ointment.

[0248] Experimental example

[0249] The crisaborole ointment prepared in Example 9 and Comparative Examples 1-2 was obtained respectively;

[0250] The above-mentioned crisaborole ointment was used to treat patients with skin inflammation, with symptoms such as redness, swelling, itching, exudation, etc.; among them, the ointment of Example 9 treated a total of 63 patients, the ointment of Comparative Example 1 treated a total of 41 patients, and the ointment of Comparative Example 2 treated a total of 36 patients;

[0251] Treatment:

[0252] Use a cotton swab to apply the ointment to the affected area 3 times a day. Continue applying for 7 days, and then follow up on the efficacy.

[0253] Criteria for judging efficacy:

[0254] Cure: All clinical symptoms disappear without recurrence;

[0255] Markedly effective: more than two-thirds of clinical symptoms disappeared;

[0256] Effective: clinical symptoms are alleviated;

[0257] Ineffective: Clinical symptoms remained unchanged or worsened.

[0258] The statistical efficacy is shown in Tables 1 to 3:

[0259] Group cure Significant effect efficient invalid Example 9 42 17 4 0 Comparative Example 1 21 14 5 1 Comparative Example 2 19 9 8 0

[0260] Table 2 Statistics of therapeutic effects on eczema lesions

[0261] Group cure Significant effect efficient invalid Example 9 35 22 6 0 Comparative Example 1 15 12 9 5 Comparative Example 2 12 10 11 3

[0262] Table 3 Statistics of efficacy of acne lesions

[0263]

[0264]

[0265] From Tables 1 to 3, we can see that:

[0266] The crisaborole ointment prepared by the technical scheme of the present application and the comparative example has a certain therapeutic effect on different types of skin lesions. Compared with the comparative example, the crisaborole ointment prepared by the technical scheme of the present application has a significant therapeutic effect on skin lesions such as eczema and acne.

[0267] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein by equivalents. These modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be included in the scope of the claims and specification of the present invention.

[0268] The above descriptions are only some preferred embodiments of the present invention and an explanation of the technical principles used. Those skilled in the art should understand that the scope of the invention involved in the embodiments of the present invention is not limited to the technical solutions formed by a specific combination of the above technical features, but should also cover other technical solutions formed by any combination of the above technical features or their equivalent features without departing from the above inventive concept. For example, the above features are replaced with (but not limited to) technical features with similar functions disclosed in the embodiments of the present invention to form a technical solution.

Claims

1. A crisaborole ointment, characterized in that: The invention is prepared from the following raw materials in parts by weight: 5.0-7.0 parts of crisaborole, 2.0-3.0 parts of L-menthol, 1.0-2.0 parts of ascorbyl palmitate, 5.0-7.0 parts of glycerol, 10.0-15.0 parts of white vaseline, 5.0-7.0 parts of paraffin, 8.0-10.0 parts of stearic acid, 5.0-7.0 parts of liquid paraffin, 2.0-3.0 parts of silicone oil and an appropriate amount of water.

2. The crisaborole ointment according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 5.5 parts of crisaborole, 2.5 parts of L-menthol, 1.5 parts of ascorbyl palmitate, 6.0 parts of glycerol, 12.5 parts of white vaseline, 6.0 parts of paraffin, 9.0 parts of stearic acid, 6.0 parts of liquid paraffin, 2.5 parts of silicone oil and an appropriate amount of water.

3. The crisaborole ointment according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 6.5 parts of crisaborole, 3.0 parts of L-menthol, 2.0 parts of ascorbyl palmitate, 7.0 parts of glycerol, 15.0 parts of white vaseline, 7.0 parts of paraffin, 10.0 parts of stearic acid, 7.0 parts of liquid paraffin, 3.0 parts of silicone oil and an appropriate amount of water.

4. The crisaborole ointment according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 5.8 parts of crisaborole, 2.2 parts of L-menthol, 1.2 parts of ascorbyl palmitate, 5.5 parts of glycerol, 13.0 parts of white vaseline, 5.5 parts of paraffin, 8.5 parts of stearic acid, 5.5 parts of liquid paraffin, 2.2 parts of silicone oil and an appropriate amount of water.

5. The crisaborole ointment according to claim 1, characterized in that: The liquid paraffin is of medical grade and does not contain any additives.

6. The crisaborole ointment according to claim 5, characterized in that: The liquid paraffin is decolorized and deodorized.

7. The crisaborole ointment according to claim 1, characterized in that: The crisaborole is in micronized form with a particle size of less than 10 microns.

8. The crisaborole ointment according to claim 1, characterized in that: The purity of the L-menthol is greater than 98%.

9. A method for preparing the crisaborole ointment according to any one of claims 1 to 8, characterized in that: The following steps are involved: S1. The criborol and ascorbyl palmitate are mixed uniformly; S2. The L-menthol, paraffin, stearic acid and silicone oil are heated until melted; S3. The mixture obtained in step S1 is added to the melt in step S2 and stirred evenly; S4. Mix the glycerin and white vaseline and heat to 60°C to 80°C; S5. The mixture obtained in step S3 is mixed with the mixture in step S4, and stirring is continued until uniform; S6. Finally, add an appropriate amount of water and stir until completely dissolved. In step S2, the mixture of L-menthol, paraffin, stearic acid and silicone oil is stirred at 70° C. to 75° C. for 30 minutes.

10. A method for using the crisaborole ointment according to any one of claims 1 to 8, characterized in that: The crisaborole ointment is used to treat skin diseases, and the specific method of use is as follows: a. Clean the affected skin and make sure there is no obvious dirt and moisture on the affected area; b. Take an appropriate amount of Clisborole ointment and apply it to the affected skin; c. Gently massage the affected area to ensure that the ointment is evenly covered and absorbed by the skin; d. Depending on the severity of the skin disease and the need for treatment, apply 1 to 3 times a day and continue using until the symptoms are relieved or disappear.

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