Halometasone triclosan emulsifiable paste and preparation method thereof

Abstract

The invention relates to halometasone and triclosan emulsifiable paste and a preparation method thereof in the technical field of medicines. The preparation method comprises the following steps: S1, adding lauryl sodium sulfate, a stabilizer, propylene glycol and an antioxidant into water, heating and stirring to obtain a water phase, and preserving heat for later use; s2, mixing hexadecyl palmitate, stearic acid, hexadecanol, octadecanol and white vaseline, heating, stirring and melting, adding triclosan for dissolving to obtain an oil phase, and preserving heat for later use; s3, mixing the water phase and the oil phase, and cooling to obtain a cream matrix; s4, suspending halometasone in glycerol, so as to obtain a suspension; and dispersing the suspension into the cream matrix, so as to obtain the halometasone and triclosan cream. The halometasone and triclosan emulsifiable paste prepared by the method is more stable in product quality, the number of impurities is obviously reduced after long-term or high-temperature placement, and the halometasone crystal form in the emulsifiable paste is basically consistent with that of the raw materials, so that the effectiveness of the medicine is ensured.

Description

Technical Field

[0001] The present application relates to the field of medical technology, and in particular to a halometasone and triclosan cream and a preparation method thereof. Background Art

[0002] Neurodermatitis-induced chronic eczema is a common and difficult dermatological condition characterized by complex etiology, persistent symptoms, recurrence, and difficulty in cure. Clinically, neurodermatitis-induced chronic eczema presents as thickening, cracking, infiltration, scaling, or lichenification of the skin, accompanied by varying degrees of pruritus. During episodes, patients experience itching and scratching, which in turn leads to thickening of the skin, creating a vicious cycle that makes complete cure difficult.

[0003] The immunological nature of eczema is a delayed-type hypersensitivity reaction caused by a combination of factors. After interaction with the corresponding antigen, effector Th1 cells release lymphokines and inflammatory mediators such as lysosomal enzymes, causing tissue damage and resulting in clinically visible symptoms such as skin redness, swelling, and itching. Halometasone is a topical glucocorticoid. Its halogen group enhances the drug's affinity for target cells and tissues. By binding to steroid receptors, the drug molecule can alter the expression of eczema-associated hypersensitivity proteins and act on inflammatory cells and lysosomes, modulating the inflammatory response. Triclosan, chemically known as 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 5-chloro-2-(2,2-dichlorophenoxy)phenol, is a broad-spectrum, highly effective antimicrobial agent. Triclosan has broad and effective killing and inhibitory effects against Gram-positive and Gram-negative bacteria, yeasts, viruses, and both antibiotic-resistant and non-antibiotic-resistant bacteria. It is widely used in various cream formulations and, in combination with halometasone, is used to treat neurodermatitis and chronic eczema.

[0004] US Patent No. 4512987A discloses a halometasone-triclosan cream. The preparation method comprises: dissolving sodium lauryl sulfate, EDTA, and propylene glycol in water to prepare an aqueous phase; stirring and melting cetyl palmitate, stearic acid, octadecanol, and white petrolatum; adding triclosan and ascorbyl palmitate and dissolving them completely to prepare an oil phase; mixing the aqueous and oil phases and cooling; suspending halometasone in glycerol; and evenly dispersing the suspension in a portion of the cooled cream. The remaining cream is then added and uniformly dispersed. The halometasone-triclosan cream prepared by this method has poor stability of related substances, and the types and amounts of impurities significantly increase after long-term or high-temperature storage.

[0005] Patent CN201710839152.4 discloses a halometasone cream. The formula and preparation process of this cream are roughly the same as those of patent US4512987A. In both processes, the halometasone drug phase is dispersed into the cooled cream base after preparing the cream base. The difference is that the drug phase preparation step in patent CN201710839152.4 is to dissolve the halometasone in propylene glycol and then disperse it. The stability of the related substances in the preparation prepared according to this patent is improved to a certain extent, but the halometasone crystal form in the preparation is inconsistent with the raw material, which affects the effectiveness of the drug.

[0006] Therefore, it is necessary to provide a new preparation method of halometasone triclosan cream. Summary of the Invention

[0007] In order to address the deficiencies of the prior art, the present application provides a halometasone triclosan cream and a preparation method thereof. The product quality of the halometasone triclosan cream prepared by the preparation method described in the present application is more stable, the increase in the number of impurities after long-term or high-temperature storage is significantly reduced, and the halometasone crystal form in the cream is basically consistent with the raw material, thereby ensuring the effectiveness of the drug.

[0008] To this end, the first aspect of the present application provides a method for preparing halometasone triclosan cream, the method comprising the following steps: S1, adding sodium lauryl sulfate, stabilizer, propylene glycol and antioxidant to water, heating and stirring until dissolved to obtain an aqueous phase, and keeping the temperature for later use; S2, cetyl palmitate, stearic acid, cetyl alcohol, stearyl alcohol and white vaseline are mixed, heated and stirred to melt, and triclosan is added to dissolve to obtain an oil phase, which is kept warm for later use; S3, mixing the aqueous phase and the oil phase and cooling the mixture to obtain a cream base; S4, suspending halometasone in glycerol to obtain a suspension; and dispersing the suspension in the cream base to prepare the halometasone triclosan cream.

[0009] Since halometasone is sensitive to oxygen and is easily oxidized during storage, thereby producing a complex variety of impurities, the method described in this application adds an antioxidant during the preparation of halometasone triclosan cream. The added antioxidant can protect the halometasone in the cream preparation, preventing it from rapid oxidative degradation, thereby improving the stability of product quality. Furthermore, the inventors of this application have found through research that after being prepared into a cream preparation, halometasone is mainly distributed in the aqueous matrix of the cream. Therefore, by adding an antioxidant to the aqueous phase, halometasone can be fully contacted with the antioxidant, which can further slow down the degradation of halometasone, thereby more effectively protecting halometasone, significantly reducing the increase in the number of impurities after the product is placed under high temperature and high humidity conditions, and the quality of the product is more stable.

[0010] Furthermore, the inventors of the present application have found through research that halometasone has poor solubility in both the aqueous and oil phases. If halometasone is first dispersed in propylene glycol, halometasone will undergo dissolution and precipitation. At this time, its crystal form is likely to change, and there is a halometasone crystal transformation phenomenon, which causes the halometasone crystal form in the product to be inconsistent with the raw material, affecting the effectiveness of the drug. To this end, the present application first suspends halometasone in a glycerol solution, and then disperses the glycerol suspension containing halometasone in the cream base, which not only improves the dispersion uniformity of halometasone, but also effectively avoids the occurrence of halometasone crystal transformation phenomenon.

[0011] In some embodiments, based on 10 g of halometasone triclosan cream, the composition of the raw materials for preparing the halometasone triclosan cream is as follows: Halometasone 4-6 mg; triclosan 80-120 mg; antioxidant 4-6 mg; hexadecanol 400-500 mg; hexadecyl palmitate 350-450 mg; sodium lauryl sulfate 80-120 mg; stabilizer 8-12 mg; glycerin 550-650 mg; propylene glycol 500-600 mg; stearic acid 350-450 mg; octadecyl alcohol 400-500 mg; white petrolatum 450-550 mg; and the balance water.

[0012] In the present application, the halometasone and triclosan added to the raw materials for preparing the halometasone-triclosan cream are effective active ingredients. Through the combination of the two, the prepared cream can be used to treat neurodermatitis and chronic eczema; the cetyl alcohol, stearyl alcohol and sodium lauryl sulfate are emulsifiers, which can disperse oil and water with each other and make the two mix evenly, thereby enhancing the stability and quality of the product; the cetyl palmitate and stearic acid are oil phase matrices, and the glycerol and propylene glycol are water phase / moisturizers; the stabilizer is an auxiliary agent of the antioxidant, usually a chelating agent, which can enhance the effect of the antioxidant by preferentially reacting with metal ions; the water can be purified water, which is the water phase.

[0013] By adopting the above-mentioned composition of raw materials for preparation, the present application can ensure that the prepared product has stable quality, good therapeutic effect, and excellent rheological properties and in vitro release properties.

[0014] In some preferred embodiments, based on 10 g of halometasone triclosan cream, the composition of the raw materials for preparing the halometasone triclosan cream is as follows: Halometasone 5mg; triclosan 100mg; antioxidant 5mg; cetyl alcohol 450mg; cetyl palmitate 400mg; sodium lauryl sulfate 100mg; stabilizer 10mg; glycerin 600mg; propylene glycol 550mg; stearic acid 400mg; octadecyl alcohol 450mg; white petrolatum 500mg; and water 6430mg.

[0015] This application further improves the comprehensive performance of the prepared product by optimizing the content of each component in the preparation raw materials.

[0016] In some embodiments, the antioxidant is selected from at least one of ascorbyl palmitate, L-ascorbic acid, sodium bisulfite, and anhydrous sodium sulfate.

[0017] In some preferred embodiments, the antioxidant is ascorbyl palmitate.

[0018] The antioxidant added in the present application can protect the halometasone in the cream preparation, avoid its rapid oxidative degradation, and improve the stability of product quality.

[0019] In some embodiments, the stabilizer is selected from at least one of disodium edetate, tartaric acid, and citric acid.

[0020] In the present application, the stabilizer can chelate metal ions, thereby strengthening the effect of the metal ions and further improving the stability and quality of the product.

[0021] In some preferred embodiments, the stabilizer is a mixture of disodium edetate (disodium EDTA) and citric acid; the mass ratio of disodium edetate (disodium EDTA) to citric acid in the mixture is (1-3):1, preferably 2:1.

[0022] The inventors of this application have discovered through research that the use of the stabilizer composition described above can enhance the stabilizer's effectiveness, thereby improving product stability and quality. Furthermore, the citric acid in the stabilizer can also eliminate skin pigmentation and mitigate the side effects of halometasone-triclosan cream, thereby making the halometasone-triclosan cream prepared in this application more suitable for the treatment of neurodermatitis and chronic eczema.

[0023] In some embodiments, in step S1, the temperature of the water phase is 65-75°C; in step S2, the temperature of the oil phase is 65-75°C.

[0024] In some specific embodiments, in step S1, the temperature of the water phase is 70°C; in step S2, the temperature of the oil phase is 70°C.

[0025] The present application controls the temperature of the water phase and the oil phase within the above range, which is more conducive to the subsequent mixing of the water phase and the oil phase.

[0026] In some embodiments, in step S3, the temperature of the cream base obtained after cooling is 40-46°C.

[0027] Since the important factor affecting the crystal form of the raw material drug is the temperature of its preparation process, the present application also controls the drug phase dispersion temperature. The present application can further avoid the occurrence of halometasone crystal transformation by controlling the temperature of the cooled cream base within the above range, thereby improving the effectiveness of the drug. If the temperature of the cooled cream base is too high, such as higher than 46°C, when the halometasone-containing suspension is subsequently dispersed therein, it is easy to cause halometasone crystal transformation; if the temperature of the cooled cream base is too low, such as lower than 40°C, the fluidity of the cream base will deteriorate, which is not conducive to the subsequent uniform dispersion of the halometasone suspension.

[0028] In some embodiments, in step S4, the temperature of the glycerol is 20-25°C.

[0029] The inventors of the present application have discovered through research that when halometasone is first dispersed in propylene glycol and then dispersed in a cream base to prepare a cream, halometasone crystal transformation occurs, resulting in the halometasone crystal form in the product being inconsistent with the raw material, affecting the effectiveness of the drug. In order to avoid halometasone crystal transformation and ensure the effectiveness of the drug, the inventors of the present application creatively dispersed halometasone in glycerol at room temperature (20-25°C), and the suspension was further dispersed in the cream base at a temperature of 40-46°C after cooling, which can effectively avoid the occurrence of halometasone crystal transformation and improve the effectiveness of the drug.

[0030] The second aspect of the present application provides a halometasone and triclosan cream prepared by the method described in the first aspect of the present application.

[0031] The method described in the present application is to add an antioxidant to the aqueous phase, which can effectively slow down the degradation of halometasone, and to protect halometasone more effectively, so that the number of impurities in the product after being placed at high temperature is significantly reduced, and the quality of the product is more stable. At the same time, by dispersing halometasone in glycerol at room temperature (20-25 ° C), and further dispersing the suspension in the cream matrix at a temperature of 40-46 ° C after cooling, the occurrence of halometasone crystallization phenomenon can be effectively avoided, thereby improving the effectiveness of the drug. Therefore, the halometasone triclosan cream prepared by the method described in the present application has the advantages of good product quality stability and high efficacy.

[0032] The beneficial technical effects of the present application are as follows: the method for preparing the halometasone triclosan cream provided by the present application can more effectively protect the halometasone by adding an antioxidant to the aqueous phase, thereby making the quality of the product more stable; at the same time, by dispersing the halometasone in glycerol at room temperature (20-25°C), and further dispersing the suspension in the cream matrix at a temperature of 40-46°C after cooling, the occurrence of the halometasone crystal transformation phenomenon can be effectively avoided, thereby improving the effectiveness of the drug. In addition, by optimizing the raw material composition of the halometasone triclosan cream, the obtained product not only has stable quality and good therapeutic effect, but also has excellent rheological properties and in vitro release characteristics, and has few side effects, and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is the Raman spectrum of the halometasone and triclosan cream prepared in Example 1.

[0034] Figure 2 This is the Raman spectrum of the halometasone and triclosan cream prepared in Comparative Example 2.

[0035] Figure 3 This is the Raman spectrum of halometasone API.

[0036] Figure 4 These are the droplet particle size test results of the self-developed preparation and reference preparation ① in Test Example 4. DETAILED DESCRIPTION

[0037] To make this application easier to understand, the following examples will be used to further illustrate this application. These examples are for illustrative purposes only and are not intended to limit the scope of application of this application. Unless otherwise specified, the raw materials or components used in this application can be obtained through commercial channels or conventional methods.

[0038] Example 1: Preparation of Halometasone-Triclosan Cream (1) Raw material composition The raw material composition of the halometasone triclosan cream prepared in this embodiment is shown in Table 1.

[0039] Table 1 Name of raw materials Add to 10g prescription amount Halometasone 5mg Triclosan 100mg Ascorbyl palmitate 5mg Cetyl alcohol 450mg Cetyl Palmitate 400mg Sodium lauryl sulfate 100mg Edetate disodium 10mg glycerin 600mg Propylene glycol 550mg stearic acid 400mg Octadecanol 450mg White Vaseline 500mg purified water 6430mg (2) Preparation process Prepare the aqueous phase: Add sodium lauryl sulfate, disodium edetate, propylene glycol, and ascorbyl palmitate to purified water. Place in a 70°C water bath and stir at an appropriate speed to disperse the mixture. Prepare the aqueous phase and keep warm until ready to use.

[0040] Preparation of oil phase: Add cetyl palmitate, stearic acid, cetyl alcohol, stearyl alcohol and white vaseline into a beaker, heat to 70°C and stir to melt, then add triclosan and dissolve completely to prepare the oil phase, and keep warm for use.

[0041] Add the oil phase to the water phase while stirring. After the addition is completed, continue stirring for 35 minutes. After emulsification is complete, cool to 43°C to obtain a cream base.

[0042] Halometasone is added to glycerol at room temperature (20°C) and stirred to obtain a suspension; the suspension is then added to a cream base cooled to 43°C while stirring to uniformly disperse the suspension in the cooled cream base, and the mixture is stirred until condensed to obtain a halometasone triclosan cream.

[0043] Example 2: Preparation of Halometasone-Triclosan Cream (1) Raw material composition The raw material composition is basically the same as that in Example 1, except that the stabilizer 10 mg of edetate disodium in Example 1 is replaced by a mixture of 5 mg of edetate disodium and 5 mg of citric acid, and the mass ratio of edetate disodium to citric acid in the mixture is 1:1.

[0044] (2) Preparation process The preparation process is basically the same as in Example 1, except that the preparation process of the aqueous phase is as follows: Prepare the aqueous phase: Add sodium lauryl sulfate, disodium edetate, citric acid, propylene glycol, and ascorbyl palmitate to purified water. Stir in a 70°C water bath at an appropriate speed to disperse the mixture. Keep warm until ready to use.

[0045] Example 3: Preparation of Halometasone-Triclosan Cream (1) Raw material composition The raw material composition is basically the same as that in Example 1, except that the stabilizer 10 mg of edetate disodium in Example 1 is replaced by a mixture of 6.7 mg of edetate disodium and 3.3 mg of citric acid, and the mass ratio of edetate disodium to citric acid in the mixture is 2:1.

[0046] (2) Preparation process The preparation process is basically the same as in Example 1, except that the preparation process of the aqueous phase is as follows: Prepare the aqueous phase: Add sodium lauryl sulfate, disodium edetate, citric acid, propylene glycol, and ascorbyl palmitate to purified water. Stir in a 70°C water bath at an appropriate speed to disperse the mixture. Keep warm until ready to use.

[0047] Example 4: Preparation of Halometasone-Triclosan Cream (1) Raw material composition The raw material composition is basically the same as that in Example 1, except that the stabilizer 10 mg of edetate disodium in Example 1 is replaced by a mixture of 7.5 mg of edetate disodium and 2.5 mg of citric acid, and the mass ratio of edetate disodium to citric acid in the mixture is 3:1.

[0048] (2) Preparation process The preparation process is basically the same as in Example 1, except that the preparation process of the aqueous phase is as follows: Prepare the aqueous phase: Add sodium lauryl sulfate, disodium edetate, citric acid, propylene glycol, and ascorbyl palmitate to purified water. Stir in a 70°C water bath at an appropriate speed to disperse the mixture. Keep warm until ready to use.

[0049] Example 5: Preparation of Halometasone-Triclosan Cream (1) Raw material composition The raw material composition is basically the same as that in Example 1, except that the stabilizer 10 mg of edetate disodium in Example 1 is replaced by 10 mg of citric acid.

[0050] (2) Preparation process The preparation process is basically the same as in Example 1, except that the preparation process of the aqueous phase is as follows: Prepare the aqueous phase: Add sodium lauryl sulfate, citric acid, propylene glycol, and ascorbyl palmitate to purified water. Stir in a 70°C water bath at an appropriate speed to disperse the mixture. Keep warm until ready to use.

[0051] Comparative Example 1: Preparation of Halometasone and Triclosan Cream (1) Raw material composition The raw material composition is the same as that of Example 1.

[0052] (2) Preparation process Preparation of the aqueous phase: Add sodium lauryl sulfate, disodium edetate, and propylene glycol to purified water. Place in a 70°C water bath and stir at an appropriate speed to disperse the mixture. Prepare the aqueous phase and keep warm until ready to use.

[0053] Preparation of oil phase: Add cetyl palmitate, stearic acid, cetyl alcohol, stearyl alcohol and white vaseline into a beaker, heat to 70°C and stir to melt, then add triclosan and ascorbyl palmitate and dissolve completely to prepare the oil phase, and keep warm for use.

[0054] Add the oil phase to the water phase while stirring. After the addition is completed, continue stirring for 35 minutes. After emulsification is complete, cool to 43°C to obtain a cream base.

[0055] Halometasone is added to glycerol at room temperature (20°C) and stirred to obtain a suspension; the suspension is then added to a cream base cooled to 43°C while stirring to uniformly disperse the suspension in the cooled cream base, and the mixture is stirred until condensed to obtain a halometasone triclosan cream.

[0056] Comparative Example 2: Preparation of Halometasone-Triclosan Cream (1) Raw material composition The raw material composition is the same as that of Example 1.

[0057] (2) Preparation process Preparation of the aqueous phase: Add sodium lauryl sulfate, disodium edetate, and glycerin to purified water. Place in a 70°C water bath and stir at an appropriate speed to disperse the mixture. Prepare the aqueous phase and keep warm for later use.

[0058] Preparation of oil phase: Add cetyl palmitate, stearic acid, cetyl alcohol, stearyl alcohol and white vaseline into a beaker, heat to 70°C and stir to melt, then add triclosan and ascorbyl palmitate and dissolve completely to prepare the oil phase, and keep warm for use.

[0059] Add the oil phase to the water phase while stirring. After the addition is completed, continue stirring for 35 minutes. After emulsification is complete, cool to 55°C to obtain a cream base.

[0060] Halometasone is added to propylene glycol and stirred to dissolve to obtain a halometasone solution; the halometasone solution is then added to a cream base cooled to 55°C, while stirring to uniformly disperse the solution in the cooled cream base, and the solution is stirred until condensed to obtain a halometasone triclosan cream.

[0061] Test Example 1: High Temperature and High Humidity Stability Test The halometasone and triclosan creams prepared in Examples 1-5 and Comparative Examples 1-2 were placed at a temperature of 50° C. and a relative humidity of 90% for 10 days according to commercial packaging. Samples were taken on the 0th day, the 4th day, and the 10th day for detection of related substances. The results are shown in Table 2.

[0062] Table 2 As can be seen from the test results of Table 2, the stability of the halometasone triclosan cream prepared in Examples 1-5 of the present application is significantly better than that of Comparative Example 1, indicating that in the preparation process of halometasone triclosan cream, adding an antioxidant to the aqueous phase can slow down the degradation rate of halometasone and improve the high temperature and high humidity stability of halometasone triclosan cream. At the same time, it can be seen from the test results of Examples 1-5 that when the stabilizer added to the raw material is a mixture of disodium edetate and citric acid, and the mass ratio of disodium edetate and citric acid in the mixture is 2: 1, it helps to further improve the stability of halometasone triclosan cream, and the product has less impurity content after being placed under high temperature and high humidity conditions, and has better stability and quality. The high temperature stability of the halometasone triclosan cream prepared by the method described in Comparative Example 2 is also better than that of Comparative Example 1, but the high temperature stability of the halometasone triclosan cream prepared by Examples 1-4 is slightly worse, indicating that the preparation method in Comparative Example 2 can also improve the high temperature stability of the prepared halometasone triclosan cream to a certain extent.

[0063] Test Example 2 Raman spectroscopy was performed on the halometasone triclosan cream and halometasone bulk drug prepared in Example 1 and Comparative Example 2. The detection was entrusted to Hangzhou Lingye Pharmaceutical Technology Co., Ltd. The Raman spectra after the detection were as follows: Figure 1-3 shown.

[0064] from Figure 1-3 It can be seen from the Raman spectrum data in that the crystal form of the sample prepared in Comparative Example 2 is quite different from the crystal form of the raw material drug, while the crystal form of the halometasone triclosan cream prepared in Example 1 is basically consistent with the raw material drug, and has obvious halometasone crystal characteristic peaks, indicating that dispersing halometasone in a glycerol solution at room temperature (20-25°C) and dispersing the halometasone suspension in a cream matrix at a lower temperature (40-46°C) can effectively avoid the crystal transformation of halometasone during the preparation process, improve the effectiveness of the drug, and make the product quality better.

[0065] Test Example 3 The rheological properties of the halometasone and triclosan cream (self-prepared formulation) prepared in Example 1, as well as reference preparations ① (licensed by Pro Farma AG / Recordati AG, origin: Greece) and ② (licensed by Pro Farma AG / Recordati AG, origin: Greece) of different production batches were tested. The flow curve test results are shown in Table 3, the yield stress test results are shown in Table 4, and the linear viscoelastic region test results are shown in Table 5.

[0066] Table 3 Table 4 Table 5 As shown in Table 3, the viscosity of the self-made preparation and the reference preparation ① decreased significantly with the increase of shear rate. -1 ) to high shear rate (100s -1 ), the viscosity change trend of the self-developed preparation and the reference preparation ① was consistent. This result shows that the stability of the self-developed preparation and the reference preparation during product storage, transportation, stirring, and shaking is consistent with that of the reference preparation.

[0067] Yield stress, the critical stress at which a sample begins or stops flowing, can be used to assess the spreadability of topical skin preparations during use and the ease of product filling. The yield stress values ​​in Table 4 indicate that the yield stress of the self-made formulation is not significantly different from that of the two reference formulations, indicating that the self-made formulation does not affect extrusion, filling, or application.

[0068] Generally speaking, when a sample is subjected to an external force, it slowly deforms, exhibiting viscous behavior. After the deforming force is removed, the sample gradually returns to its original structure, exhibiting elastic behavior. Good viscosity ensures that topical skin preparations adhere tightly to the application site, preventing them from falling off and flowing easily during use. Good elasticity also enhances the storage stability of the preparation. The linear viscoelastic region in Table 5 shows that the viscoelasticity test results for the self-prepared preparation and the two reference preparations are relatively close, with no significant differences. This indicates that the self-prepared preparations are similar to the reference preparations in terms of both adherence to the application site and storage stability.

[0069] In summary, the rheological properties of the self-developed formulation are not significantly different from those of the reference formulation, and the rheological properties are excellent.

[0070] Test Example 4 The particle size of the halometasone triclosan cream (self-made preparation) and the reference preparation ① prepared in Example 1 was tested. The detection process referred to the particle size inspection method (Appendix IXE of Part II of the Chinese Pharmacopoeia 2015 Edition). The droplet particle size test results of the self-made preparation and the reference preparation-2109792 are as follows: Figure 4 and shown in Table 6.

[0071] Table 6 from Figure 4 As shown in Table 6, the droplet size distribution of the self-made preparation is not significantly different from that of the reference preparation. The droplet size is small and evenly distributed, indicating that the preparation process of the self-made preparation is excellent.

[0072] Test Example 5 The halometasone triclosan cream (self-made preparation) prepared in Example 1 and the reference preparation ① were placed at a temperature of 50°C and a relative humidity of 60% according to commercial packaging for 10 days. Samples were taken on the 0th day and the 10th day for detection of related substances. The results are shown in Table 7.

[0073] Table 7 As can be seen from Table 7, after being placed at a temperature of 50°C and a relative humidity of 60% for 10 days, the main impurity that increased in the reference preparation ① and the self-prepared preparation was impurity A, and the growth rate of impurity A in the self-prepared preparation (Example 1) was significantly lower than that in the reference preparation ①, indicating that the self-prepared preparation prepared in the present application is more stable and has better high-temperature stability.

[0074] Test Example 6 The in vitro release properties of the halometasone and triclosan cream (self-made formulation) prepared in Example 1 and the reference preparation ① were tested. The in vitro release test method was the IVRT method. Specific parameter information during the test process is shown in Table 8. After testing, the in vitro release results of halometasone in the self-made formulation and the reference preparation ① are shown in Table 9, and the in vitro release results of triclosan in the self-made formulation and the reference preparation ① are shown in Table 10.

[0075] Table 8: IVRT method parameter information Table 9 As shown in Table 9, the average release rate of halometasone in the self-prepared preparation was basically consistent with that of the reference preparation, the RSD of the release rate met the requirements, and the confidence interval was between 75% and 133.33%. It can be considered that its in vitro release behavior was equivalent to that of the reference preparation.

[0076] Table 10 As shown in Table 10, the average release rate of triclosan in the self-developed preparation is basically consistent with that of the reference preparation, the RSD of the release rate meets the requirements, and the confidence interval is between 75% and 133.33%. It can be considered that its in vitro release behavior is equivalent to that of the reference preparation.

[0077] It should be noted that the embodiments described above are only used to explain the present application and do not constitute any limitation to the present application. The present application has been described with reference to typical embodiments, but it should be understood that the words used therein are descriptive and explanatory words, rather than restrictive words. The present application may be modified as specified within the scope of the claims of the present application, and the invention may be revised without departing from the scope and spirit of the present application. Although the present application described therein relates to specific methods, materials and embodiments, it does not mean that the present application is limited to the specific examples disclosed therein. On the contrary, the present application can be extended to all other methods and applications with the same function.

Claims

1. A method for preparing halometasone triclosan cream, characterized in that: The method comprises the following steps: S1, adding sodium lauryl sulfate, stabilizer, propylene glycol and antioxidant into water, heating and stirring to obtain an aqueous phase, and keeping the temperature for later use; S2, cetyl palmitate, stearic acid, cetyl alcohol, octadecyl alcohol and white vaseline are mixed, heated and stirred to melt, and triclosan is added to dissolve to obtain an oil phase, which is kept warm for later use; S3, mixing the water phase and the oil phase and cooling the mixture to obtain a cream base; S4, suspending halometasone in glycerol to obtain a suspension; dispersing the suspension in the cream base to prepare the halometasone triclosan cream.

2. The method according to claim 1, characterized in that Based on 10 g of halometasone triclosan cream, the composition of the raw materials for preparing the halometasone triclosan cream is as follows: Halometasone 4-6 mg; triclosan 80-120 mg; antioxidant 4-6 mg; hexadecanol 400-500 mg; hexadecyl palmitate 350-450 mg; sodium lauryl sulfate 80-120 mg; stabilizer 8-12 mg; glycerin 550-650 mg; propylene glycol 500-600 mg; stearic acid 350-450 mg; octadecyl alcohol 400-500 mg; white vaseline 450-550 mg; and the balance water.

3. The method according to claim 2, characterized in that Based on 10 g of halometasone triclosan cream, the composition of the raw materials for preparing the halometasone triclosan cream is as follows: Halometasone 5mg; triclosan 100mg; antioxidant 5mg; hexadecanol 450mg; hexadecanol palmitate 400mg; sodium lauryl sulfate 100mg; stabilizer 10mg; glycerin 600mg; propylene glycol 550mg; stearic acid 400mg; octadecyl alcohol 450mg; white vaseline 500mg; and water 6430mg.

4. The method according to any one of claims 1 to 3, characterized in that: The antioxidant is selected from at least one of ascorbyl palmitate, L-ascorbic acid, sodium bisulfite and anhydrous sodium sulfate.

5. The method according to any one of claims 1 to 3, characterized in that: The stabilizer is selected from at least one of disodium edetate, tartaric acid and citric acid.

6. The method according to claim 5, characterized in that The stabilizer is a mixture of disodium edetate and citric acid; and the mass ratio of disodium edetate to citric acid in the mixture is (1-3):

1.

7. The method according to any one of claims 1 to 3, characterized in that: In step S1, the temperature of the water phase is 65-75°C; in step S2, the temperature of the oil phase is 65-75°C.

8. The method according to any one of claims 1 to 3, characterized in that: In step S3, the temperature of the cream base obtained after cooling is 40-46°C.

9. The method according to any one of claims 1 to 3, characterized in that: In step S4, the temperature of the glycerol is 20-25°C.

10. A halometasone and triclosan cream prepared by the method according to any one of claims 1 to 9.

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