Riptacaine emulsifiable paste as well as preparation method and application of riptacaine emulsifiable paste

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and relates to a riptacaine cream as well as a preparation method and application thereof, and the preparation method of the riptacaine cream comprises the following steps: preparing carbomer gel, preparing an oil phase, preparing a water phase, primarily emulsifying, homogenizing and gelating, finely homogenizing and filling. According to the invention, polyoxyethylene (54) hydrogenated castor oil is innovatively used as an auxiliary material, triple functions of a co-melting solvent, an emulsifying agent and a stabilizing agent are realized at the same time, and any liquid grease, solvent or other surfactants do not need to be additionally added in the prescription. Through a unique'water-gel-oil 'composite structure design, oil drops are physically wrapped by a carbomer gel network and are positioned in network pores, so that the mechanical stability superior to that of a conventional emulsion is provided, and no layering is generated through high-speed centrifugal test verification. In conclusion, the invention develops the riptacaine preparation which has the advantages of few types of auxiliary materials, higher stability, quicker effect taking and capability of expanding a new dosage form and a new process.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, and particularly relates to a lipoprotein dicaine cream, its preparation method and application. Background Technology

[0002] Lidocaine and prilocaine are commonly used local anesthetics. When mixed in a certain proportion, they form a eutectic mixture, which lowers their respective melting points, allowing them to liquefy at room temperature and easily penetrate the skin to take effect. Currently, commercially available prilocaine creams (such as EMLA®) mainly use an oil-in-water (O / W) cream base, typically containing liquid oils, emulsifiers, stabilizers, and other excipients.

[0003] The existing production processes and formulas have some shortcomings: 1. Numerous types of excipients: Traditional formulations require the use of various oils and surfactants to form stable creams, which increases the risk of unknown impurities and the complexity of quality control.

[0004] 2. Poor physical stability: It is prone to phase separation, oil separation, demulsification and other phenomena during storage or transportation, which affect the efficacy and appearance of the medicine.

[0005] 3. There is room for improvement in drug penetration efficiency: Although eutectic compounds themselves have a permeation-enhancing effect, their penetration rate and depth are still difficult to meet the needs of some deep analgesia.

[0006] 4. Limited dosage form: Primarily ointments or creams, which cannot provide a continuous, closed administration environment, thus limiting its application scenarios.

[0007] Therefore, there is an urgent need to develop a new formulation and process for lipofuscin with fewer excipients, higher stability, faster onset of action, and the ability to expand into new dosage forms. Summary of the Invention

[0008] The main objective of this invention is to provide a liposome cream, its preparation method, and its application, in order to overcome the shortcomings of the prior art.

[0009] To achieve the aforementioned objectives, the technical solution adopted by this invention includes: According to a first aspect of the present invention, a method for preparing levodopacaine cream is provided, comprising the following steps: S1. Disperse carbomer homopolymer type B in purified water, stir and swell to form carbomer aqueous solution for later use; S2. Lidocaine, prilocaine and a nonionic surfactant with an HLB value of 14-16 are stirred and melted at 60-85°C to form a transparent and homogeneous oil phase mixture. S3. Heat the purified water to 60-85℃ and use it as the aqueous phase for later use; S4. Primary emulsification: Under stirring, the aqueous phase obtained in step S3 is added to the oil phase mixture obtained in step S2 to form a primary emulsion. S5. Homogenize the primary emulsion obtained in step S4 at 1000-5000 rpm for 2-15 minutes, then slowly add the carbomer aqueous solution obtained in step S1 while stirring, maintain the temperature and mix evenly, adjust the pH of the system to 7.0-9.0 with sodium hydroxide solution to obtain a mixture. S6. Homogenize the mixture obtained in step S5, controlling the homogenization speed and cumulative homogenization time until a stable cream system is formed, i.e., a qualified intermediate product is obtained. S7. Filling: Fill and package the qualified intermediate product obtained in step S6 to obtain the liposome cream.

[0010] Furthermore, the nonionic surfactant mentioned in step S2 is polyoxyethylene hydrogenated castor oil.

[0011] Furthermore, step S2 also includes adding a penetration enhancer, wherein the penetration enhancer is azone or oleic acid; The amount of azone added is 0.1% to 0.5% of the total mass of the cream; Alternatively, the ratio of the amount of oleic acid added to the sum of the molar amounts of lidocaine and prilocaine is 1:1 to 1:2.

[0012] Furthermore, the fine homogenization described in step S6 is performed using a high-pressure homogenizer with a homogenization pressure of 500-1500 bar and a homogenization cycle of 2-5 times.

[0013] According to a second aspect of the present invention, a levodopacaine cream prepared by any of the above methods is provided, characterized in that the cream forms a water-gel-oil composite system, wherein the oil phase droplets are encapsulated by a three-dimensional carbomer gel network; and as observed by cryo-scanning electron microscopy, the carbomer gel network forms pores with a pore size of 5-50 μm, and the oil phase droplets are positioned within the pores.

[0014] Furthermore, the average particle size D90 of the oil phase droplets is less than 2 μm.

[0015] Furthermore, the cream was centrifuged at 4000 rpm for 15 minutes and showed no stratification or emulsification.

[0016] Furthermore, by weight, the lidocaine cream is composed of the following components: 2-4 parts lidocaine, 2-4 parts prilocaine, 1-3 parts polyoxyethylene (54) hydrogenated castor oil, 0.2-0.4 parts carbomer homopolymer type B, 0.01-0.1 parts sodium hydroxide, and 88.5-94.79 parts purified water.

[0017] According to a third aspect of the present invention, a levofloxacin gel patch is provided, wherein the levofloxacin gel patch is prepared by adding 1-3% of the total mass of the levofloxacin cream according to any one of claims 5-8 to the levofloxacin cream, and then mixing, coating and drying the mixture to obtain the levofloxacin gel patch.

[0018] Furthermore, the inorganic gelling agent is magnesium aluminum silicate or magnesium lithium silicate.

[0019] Compared with the prior art, the advantages of the present invention include: This invention provides a lipofuscin cream, its preparation method, and its application. This invention innovatively uses polyoxyethylene (54) hydrogenated castor oil as an excipient, simultaneously achieving the triple functions of eutectic solvent, emulsifier, and stabilizer. No additional liquid oils, solvents, or other surfactants are required in the formulation, greatly reducing the risk of impurities and allergies caused by complex excipients. Through a unique "water-gel-oil" composite structure design, the carbomer gel network physically encapsulates oil droplets, positioning them within the network pores, providing mechanical stability exceeding that of conventional emulsions. High-speed centrifugation tests verified no stratification. The selective addition of trace amounts of azone or oleic acid creates a synergistic penetration-enhancing effect with the base system. Oleic acid can also form ion pairs with the drug, further promoting drug transport across the skin. Combined with the ultrafine particle size (D90 < 2 μm) obtained through high-pressure homogenization, the absorption surface area of ​​the drug is greatly increased, thereby significantly accelerating the onset of action and enhancing efficacy. Employing a stepped homogenization process, particularly the high-pressure homogenization step, emulsions with fine and uniform particle size distribution can be efficiently obtained at low temperatures, significantly improving product quality attributes (CQAs) and ensuring high batch-to-batch consistency. Based on the cream's excellent room-temperature stability, it can be easily further formulated into a gel patch, achieving dosage form innovation. The patch provides a continuous, sealed drug delivery environment, suitable for a wider range of clinical scenarios requiring long-acting analgesia, such as postherpetic neuralgia and pre-needle aspiration pretreatment, demonstrating broad market prospects. Attached Figure Description

[0020] Various other advantages and benefits will become apparent to those skilled in the art upon reading the following detailed description of preferred embodiments. The accompanying drawings are for illustrative purposes only and are not intended to limit the invention. Furthermore, the same reference numerals denote the same parts throughout the drawings. In the drawings: Figure 1 This is a flowchart of a typical embodiment of the preparation method of lipoprotein-dicaine compound cream according to the present invention. Detailed Implementation

[0021] In view of the shortcomings of the prior art, the inventors of this invention, through long-term research and extensive practice, have proposed the technical solution of this invention. The following will further explain and illustrate this technical solution, its implementation process, and its principles.

[0022] The present invention will now be described in further detail with reference to specific embodiments. The given embodiments are merely illustrative of the invention and not intended to limit its scope. The embodiments provided below can serve as a guide for further improvements by those skilled in the art and do not constitute a limitation on the invention in any way.

[0023] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Unless otherwise specified, the materials and reagents used in the following examples are commercially available.

[0024] like Figure 1 As shown, this embodiment of the invention provides a method for preparing a liposome-based compound cream, comprising the following steps: S1. Disperse carbomer homopolymer type B in a portion of the prescribed amount (preferably 30%-60% of the total purified water amount) of purified water, and swell at 20-30℃ with a stirring rate of 100-500 rpm for 1-3 hours to form a uniform and transparent carbomer aqueous solution for later use. S2. Lidocaine, prilocaine and a nonionic surfactant with an HLB value of 14-16 are stirred and melted at 60-85°C (more preferably 70-80°C) at a stirring rate of 200-800 rpm to form a transparent and homogeneous oil phase mixture; the nonionic surfactant is polyoxyethylene (54) hydrogenated castor oil.

[0025] S3. Heat the remaining amount of purified water (i.e., the remaining part after deducting the amount used in step S1 from the total amount of purified water) to 60-85℃ (matching the temperature of the oil phase) and use it as the aqueous phase for later use. S4. At a stirring speed of 300-1000 rpm, slowly add the aqueous phase obtained in step S3 to the oil phase mixture obtained in step S2 (the volume ratio of oil phase to aqueous phase is 1:(1-3), which can be adjusted according to the actual situation) and mix to form a primary emulsion. S5. Homogenize the primary emulsion obtained in step S4 at 1000-5000 rpm (preferably 2000-4000 rpm) for 2-15 minutes (more preferably 5-10 minutes). Then, slowly add the carbomer aqueous solution obtained in step S1 under continuous stirring (stirring speed 100-300 rpm) (addition time is 5-30 minutes to avoid excessive local concentration), maintain the temperature (60-85℃) and mix evenly. Adjust the pH of the system to 7.0 to 9.0 (preferably 7.5-8.5) with 1-10 wt% sodium hydroxide solution. S6. The mixture obtained in step S5 is homogenized using a high-pressure homogenizer. The homogenization pressure is controlled at 500-1500 bar (more preferably 800-1200 bar). The homogenization cycle is 2-5 times. The mixture is stirred evenly between each cycle until a fine, uniform and stable cream system is formed. No oil droplet aggregation or layering can be observed visually. S7. Filling: The intermediate products obtained in step S6 that have passed quality inspection (such as pH, particle size, and stability meeting preset standards) are aseptically filled and sealed.

[0026] In some embodiments, step S2 further includes adding a penetration enhancer, wherein the penetration enhancer is azone or oleic acid; When the penetration enhancer is azone, its addition amount is 0.1% to 0.5% (preferably 0.2-0.4%) of the total mass of the cream. When the penetration enhancer is oleic acid, the molar ratio of its addition amount to the sum of the molar numbers of lidocaine and prilocaine is 1:1 to 1:2 (preferably 1:1.2 to 1:1.8).

[0027] In some embodiments, a lipofuscin-based composite cream prepared by the above method is provided. This cream forms a water-gel-oil composite system, wherein oil phase droplets are encapsulated by a three-dimensional network structure of carbomer gel. Cryo-scanning electron microscopy reveals that the carbomer gel network forms pores with a pore size of 5-50 μm (preferably 10-30 μm), and the oil phase droplets are positioned within these pores. The average particle size D90 of the oil phase droplets is less than 2 μm (more preferably D90 ≤ 1.5 μm, D50 ≤ 1 μm). The cream, after centrifugation at 4000 rpm for 15 minutes, shows no stratification, demulsification, or oil phase precipitation (stability indicators).

[0028] In some embodiments, a levodiamine gel patch is provided, which is prepared by adding 1% to 3% (preferably 1.5-2.5%) of an inorganic gelling agent to the levodiamine compound cream, and then stirring evenly (stirring speed 50-200 rpm, time 10-30 minutes), coating (coating thickness 0.5-3 mm), and drying (drying temperature 40-60℃, time 1-3 hours).

[0029] In some embodiments, the inorganic gelling agent is magnesium aluminum silicate or magnesium lithium silicate.

[0030] In some embodiments, the lidocaine-prilocaine compound cream is composed of the following components by mass percentage: 2-4 parts lidocaine, 2-4 parts prilocaine, 1-3 parts polyoxyethylene hydrogenated castor oil, 0.2-0.4 parts carbomer homopolymer type B, 0.01-0.1 parts sodium hydroxide, 0-0.5 parts azone, 0-0.3 parts oleic acid, and 88.5-94.79 parts purified water.

[0031] To better understand the technical solution of the present invention, the following detailed discussion is provided in conjunction with specific embodiments.

[0032] Example 1: This example provides a method for preparing a liposome-based compound cream, comprising the following steps: S1. Disperse carbomer homopolymer type B in a portion of the prescribed amount (30% of the total purified water volume) of purified water, and swell at 20°C with a stirring rate of 100 rpm for 1 hour to form a uniform and transparent carbomer aqueous solution for later use. S2. Lidocaine, prilocaine and a nonionic surfactant with an HLB value of 14 are stirred and melted at 70°C at a stirring rate of 200 rpm to form a transparent and homogeneous oil phase mixture; the nonionic surfactant is polyoxyethylene (54) hydrogenated castor oil.

[0033] S3. Heat the remaining amount of purified water (i.e., the remaining part after deducting the amount used in step S1 from the total amount of purified water) to 70°C (matching the temperature of the oil phase) and use it as the aqueous phase for later use. S4. At a stirring speed of 300 rpm, slowly add the aqueous phase obtained in step S3 to the oil phase mixture obtained in step S2 (the volume ratio of oil phase to aqueous phase is 1:1, which can be adjusted according to actual conditions) to form a primary emulsion. S5. Homogenize the primary emulsion obtained in step S4 at 2000 rpm for 5 minutes, then slowly add the carbomer aqueous solution obtained in step S1 under continuous stirring (stirring speed 100 rpm) (addition time is 5 minutes to avoid excessive local concentration), maintain the temperature (60℃) and mix evenly, and adjust the pH of the system to 7.5 with 1 wt% sodium hydroxide solution. S6. The mixture obtained in step S5 is homogenized using a high-pressure homogenizer. The homogenization pressure is controlled at 800 bar, and the number of homogenization cycles is 2. The mixture is stirred evenly between each cycle until a fine, uniform and stable cream system is formed. No oil droplets are observed to accumulate or separate into layers. S7. Filling: The intermediate products obtained in step S6 that have passed quality inspection (such as pH, particle size, and stability meeting preset standards) are aseptically filled and sealed.

[0034] A lipocaine-prilocaine composite cream prepared by the above method forms a water-gel-oil composite system, wherein the oil phase droplets are encapsulated by a three-dimensional network structure of carbomer gel. Cryo-scanning electron microscopy reveals that the carbomer gel network forms pores with a pore size of 10 μm, and the oil phase droplets are positioned within these pores. The average particle size of the oil phase droplets is D90 1.5 μm and D50 1 μm. The cream, after centrifugation at 4000 rpm for 15 minutes, shows no stratification, demulsification, or oil phase precipitation (stability indicators). The lipocaine-prilocaine composite cream is composed of the following components by mass percentage: 2 parts lidocaine, 2 parts prilocaine, 1 part polyoxyethylene hydrogenated castor oil, 0.2 parts carbomer homopolymer type B, 0.01 parts sodium hydroxide, and 88.5 parts purified water.

[0035] Also provided is a levodiamine gel patch, which is prepared by adding 1.5% of the total mass of an inorganic gelling agent to the levodiamine compound cream, followed by stirring (stirring speed 50 rpm, time 10 minutes), coating (coating thickness 0.5 mm), and drying (drying temperature 40℃, time 1 hour). The inorganic gelling agent is magnesium aluminum silicate.

[0036] Example 2: This example provides a method for preparing a liposome-based compound cream, comprising the following steps: S1. Disperse carbomer homopolymer type B in a portion of the prescribed amount (preferably 45% of the total purified water amount) of purified water, and swell at 25°C with a stirring rate of 300 rpm for 2 hours to form a uniform and transparent carbomer aqueous solution for later use. S2. Lidocaine, prilocaine and a nonionic surfactant with an HLB value of 15 are stirred and melted at 75°C at a stirring rate of 500 rpm to form a transparent and homogeneous oil phase mixture; the nonionic surfactant is polyoxyethylene (54) hydrogenated castor oil.

[0037] S3. Heat the remaining amount of purified water (i.e., the total amount of purified water used minus the amount used in step S1) to 75°C (matching the temperature of the oil phase) and use it as the aqueous phase for later use. S4. At a stirring speed of 625 rpm, slowly add the aqueous phase obtained in step S3 to the oil phase mixture obtained in step S2 (the volume ratio of oil phase to aqueous phase is 1:2, which can be adjusted according to the actual situation) to form a primary emulsion. S5. The primary emulsion obtained in step S4 is homogenized at 3000 rpm for 7.5 minutes. Then, the carbomer aqueous solution obtained in step S1 is slowly added under continuous stirring (stirring speed 200 rpm) (addition time is 17.5 minutes to avoid excessive local concentration). The temperature is maintained (72.5℃) and the mixture is mixed evenly. The pH of the system is adjusted to 8 with 5.5 wt% sodium hydroxide solution. S6. The mixture obtained in step S5 is homogenized using a high-pressure homogenizer. The homogenization pressure is controlled at 1000 bar, and the number of homogenization cycles is 3. The mixture is stirred evenly between each cycle until a fine, uniform and stable cream system is formed. No oil droplets are observed to accumulate or separate into layers. S7. Filling: The intermediate products obtained in step S6 that have passed quality inspection (such as pH, particle size, and stability meeting preset standards) are aseptically filled and sealed.

[0038] A lidocaine-prilocaine composite cream prepared by the above method is provided. This cream forms a water-gel-oil composite system, wherein the oil phase droplets are encapsulated by a three-dimensional network structure of carbomer gel. Cryo-scanning electron microscopy reveals that the carbomer gel network forms pores with a pore size of 20 μm, and the oil phase droplets are positioned within these pores. The average particle size of the oil phase droplets is D90 1 μm and D50 0.8 μm. The cream, after centrifugation at 4000 rpm for 15 minutes, shows no stratification, demulsification, or oil phase precipitation (stability indicators). In some embodiments, the lidocaine-prilocaine composite cream is composed of the following components by mass percentage: 3 parts lidocaine, 3 parts prilocaine, 2 parts polyoxyethylene hydrogenated castor oil, 0.3 parts carbomer homopolymer type B, 0.055 parts sodium hydroxide, and 91.6 parts purified water.

[0039] A levodiamine gel patch is provided, wherein the levodiamine gel patch is prepared by adding 2% (by weight of total mass) of an inorganic gelling agent to a levodiamine compound cream, and then mixing thoroughly (stirring speed 125 rpm, time 20 minutes), coating (coating thickness 1.75 mm), and drying (drying temperature 50℃, time 2 hours). The inorganic gelling agent is magnesium aluminum silicate.

[0040] Example 3: This example provides a method for preparing a liposome-based compound cream, comprising the following steps: S1. Disperse carbomer homopolymer type B in a portion of the prescribed amount (preferably 60% of the total purified water volume) of purified water, and swell at 30°C with a stirring rate of 500 rpm for 3 hours to form a uniform and transparent carbomer aqueous solution for later use. S2. Lidocaine, prilocaine and a nonionic surfactant with an HLB value of 16 are stirred and melted at 80°C and the stirring speed is 800 rpm to form a transparent and homogeneous oil phase mixture; the nonionic surfactant is polyoxyethylene (54) hydrogenated castor oil.

[0041] S3. Heat the remaining amount of purified water (i.e., the remaining part after deducting the amount used in step S1 from the total amount of purified water) to 80°C (matching the temperature of the oil phase) and use it as the aqueous phase for later use. S4. At a stirring speed of 1000 rpm, slowly add the aqueous phase obtained in step S3 to the oil phase mixture obtained in step S2 (the volume ratio of oil phase to aqueous phase is 1:3, which can be adjusted according to actual conditions) to form a primary emulsion. S5. The primary emulsion obtained in step S4 is homogenized at 4000 rpm for 10 minutes. Then, the carbomer aqueous solution obtained in step S1 is slowly added under continuous stirring (stirring speed 300 rpm) (addition time is 30 minutes to avoid excessive local concentration). The temperature is maintained at 85℃ and the mixture is mixed evenly. The pH of the system is adjusted to 8.5 with 10wt% sodium hydroxide solution. S6. The mixture obtained in step S5 is homogenized using a high-pressure homogenizer. The homogenization pressure is controlled at 1200 bar, and the number of homogenization cycles is 5. The mixture is stirred evenly between each cycle until a fine, uniform and stable cream system is formed. No oil droplets are observed to accumulate or separate into layers. S7. Filling: The intermediate products obtained in step S6 that have passed quality inspection (such as pH, particle size, and stability meeting preset standards) are aseptically filled and sealed.

[0042] A lidocaine-prilocaine composite cream prepared by the above method is provided. This cream forms a water-gel-oil composite system, wherein the oil phase droplets are encapsulated by a three-dimensional network structure of carbomer gel. Cryo-scanning electron microscopy reveals that the carbomer gel network forms pores with a pore size of 30 μm, and the oil phase droplets are positioned within these pores. The average particle size of the oil phase droplets is D90 1.5 μm and D50 1 μm. The cream, after centrifugation at 4000 rpm for 15 minutes, shows no stratification, demulsification, or oil phase precipitation (stability indicators). The lidocaine-prilocaine composite cream is composed of the following components by mass percentage: 4 parts lidocaine, 4 parts prilocaine, 3 parts polyoxyethylene hydrogenated castor oil, 0.4 parts carbomer homopolymer type B, 0.1 parts sodium hydroxide, and 94.79 parts purified water.

[0043] A levodiamine gel patch is provided, wherein the levodiamine gel patch is prepared by adding 2.5% (by weight of total mass) of an inorganic gelling agent to a levodiamine compound cream, and then mixing thoroughly (stirring speed 200 rpm, time 30 minutes), coating (coating thickness 3 mm), and drying (drying temperature 60℃, time 3 hours). The inorganic gelling agent is magnesium aluminum silicate.

[0044] Example 4: Based on the technical solution of Example 1, step S2 further includes adding a penetration enhancer, wherein the penetration enhancer is azone; when the penetration enhancer is azone, its addition amount is 0.2% of the total mass of the cream.

[0045] Example 5: Based on the technical solution of Example 1, step S2 further includes adding a penetration enhancer, wherein the penetration enhancer is azone; when the penetration enhancer is azone, its addition amount is 0.3% of the total mass of the cream.

[0046] Example 6: Based on the technical solution of Example 1, step S2 further includes adding a penetration enhancer, wherein the penetration enhancer is azone; when the penetration enhancer is azone, its addition amount is 0.4% of the total mass of the cream.

[0047] Example 7: Based on the technical solution of Example 1, step S2 further includes adding a penetration enhancer, wherein the penetration enhancer is oleic acid; when the penetration enhancer is oleic acid, the molar ratio of its added amount to the sum of the molar numbers of lidocaine and prilocaine is 1:1.2.

[0048] Example 8: Based on the technical solution of Example 1, step S2 further includes adding a penetration enhancer, wherein the penetration enhancer is oleic acid; when the penetration enhancer is oleic acid, the molar ratio of its added amount to the sum of the molar numbers of lidocaine and prilocaine is 1:1.5.

[0049] Example 9: Based on the technical solution of Example 1, step S2 further includes adding a penetration enhancer, wherein the penetration enhancer is oleic acid; when the penetration enhancer is oleic acid, the molar ratio of its added amount to the sum of the molar numbers of lidocaine and prilocaine is 1:1.8.

[0050] Comparative example: A traditional O / W type lipofuscin cream was prepared using various oils and surfactants such as white petrolatum, liquid paraffin, and lanolin, based on a commercially available formula, as a comparative example.

[0051] Experiment 1: The products of Examples 1 and 2 and the comparative product were placed in centrifuge tubes and centrifuged at 4000 rpm for 15 minutes. Results: The products of Examples 1 and 2 showed no stratification or precipitation; the comparative product showed obvious oil-water separation.

[0052] The particle size was measured using a laser particle size analyzer. Results: The average particle size D90 of the product in Example 1 was 1.8 μm; the D90 of the comparative product was 12.5 μm.

[0053] Franz diffusion cells were used, with isolated rat skin as a barrier. Results: The drug penetration rate and 24-hour cumulative penetration of the products in Examples 1 and 2 were significantly higher than those of the comparative product.

[0054] The above results demonstrate that the lipoic acid compound cream and its preparation method provided by this invention have achieved significant progress in terms of formulation simplification, physical stability, drug penetration, and dosage form innovation.

[0055] The above descriptions are merely some embodiments of the present invention. It should be noted that those skilled in the art can make other modifications and improvements without departing from the inventive concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

1. A method for preparing a lipofuscin cream, characterized in that, Includes the following steps: S1. Disperse carbomer homopolymer type B in purified water, stir and swell to form carbomer aqueous solution for later use; S2. Lidocaine, prilocaine and a nonionic surfactant with an HLB value of 14-16 are stirred and melted at 60-85°C to form a transparent and homogeneous oil phase mixture. S3. Heat the purified water to 60-85℃ and use it as the aqueous phase for later use; S4. Primary emulsification: Under stirring, the aqueous phase obtained in step S3 is added to the oil phase mixture obtained in step S2 to form a primary emulsion. S5. Homogenize the primary emulsion obtained in step S4 at 1000-5000 rpm for 2-15 minutes, then slowly add the carbomer aqueous solution obtained in step S1 while stirring, maintain the temperature and mix evenly, adjust the pH of the system to 7.0-9.0 with sodium hydroxide solution to obtain a mixture. S6. Homogenize the mixture obtained in step S5, controlling the homogenization speed and cumulative homogenization time until a stable cream system is formed, i.e., a qualified intermediate product is obtained. S7. Filling: Fill and package the qualified intermediate product obtained in step S6 to obtain the liposome cream.

2. The preparation method according to claim 1, characterized in that, The nonionic surfactant mentioned in step S2 is polyoxyethylene hydrogenated castor oil.

3. The preparation method according to claim 1 or 2, characterized in that, Step S2 also includes adding a penetration enhancer, wherein the penetration enhancer is azone or oleic acid; The amount of azone added is 0.1% to 0.5% of the total mass of the cream; Alternatively, the ratio of the amount of oleic acid added to the sum of the molar amounts of lidocaine and prilocaine is 1:1 to 1:

2.

4. The preparation method according to claim 1, characterized in that, The fine homogenization in step S6 is carried out using a high-pressure homogenizer with a homogenization pressure of 500-1500 bar and a homogenization cycle of 2-5 times.

5. A lipofuscin cream prepared by the method according to any one of claims 1-4, characterized in that, The cream forms a water-gel-oil composite system, in which the oil phase droplets are encapsulated by a three-dimensional network of carbomer gel. Cryo-scanning electron microscopy reveals that the carbomer gel network forms pores with a diameter of 5-50 μm, and the oil phase droplets are located within these pores.

6. The lipofuscin cream according to claim 5, characterized in that, The average particle size D90 of the oil phase droplets is less than 2 μm.

7. The lipofuscin cream according to claim 5 or 6, characterized in that, The cream was centrifuged at 4000 rpm for 15 minutes and showed no stratification or emulsion breakage.

8. The lipofuscin cream according to claim 5, characterized in that, The lidocaine cream, by weight, comprises the following components: 2-4 parts lidocaine, 2-4 parts prilocaine, 1-3 parts polyoxyethylene hydrogenated castor oil, 0.2-0.4 parts carbomer homopolymer type B, 0.01-0.1 parts sodium hydroxide, and 88.5-94.79 parts purified water.

9. A liposome-based gel patch, characterized in that, The levofloxacin gel patch is prepared by adding 1-3% of the total mass of the levofloxacin cream to the levofloxacin cream according to any one of claims 5-8, and then mixing, coating and drying the mixture to obtain the levofloxacin gel patch.

10. The liposome gel patch according to claim 9, characterized in that, The inorganic gelling agent is magnesium aluminum silicate or magnesium lithium silicate.

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