Norcantharidin emulsion and its preparation method and application

Abstract

The application provides a norcantharidin emulsion and a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations.The norcantharidin emulsion is prepared from the following components by weight: 0.2-0.3 parts of norcantharidin, 2.0-3.0 parts of phospholipid, 0.5-0.75 parts of a membrane stabilizer, 10-15 parts of an oil phase matrix, 0.05-0.1 parts of a co-emulsifier, 1.2-1.8 parts of an emulsifier, 6.5-7.5 parts of a gel matrix, 3.0-3.25 parts of a humectant and 950-1000 parts of water.The norcantharidin emulsion has high stability, uniform drug distribution and low irritation, can effectively isolate or relieve the direct contact irritation of the raw drug to the skin, promote the penetration of the drug through the stratum corneum of the skin, increase the retention amount of the drug in the target skin layer, reach a local effective concentration and achieve the goal of reducing irritation and increasing curative effect.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a demethylcantharidin latex, its preparation method, and its application. Background Technology

[0002] Norcantharidin (NCTD), a derivative of cantharidin (CTD), is an effective antitumor drug primarily used clinically to treat gastrointestinal malignancies such as liver cancer, esophageal cancer, and gastric cancer. Studies have shown that it interferes with cell division and induces tumor cell apoptosis by inhibiting the activity of protein phosphatase 2A (PP2) and protein phosphatase 1 (PP1). However, NCTD itself has certain drawbacks that hinder the development of its topical formulations. First, the compound has poor water solubility, leading to difficult transdermal absorption and low bioavailability. Second, and most critically, NCTD exhibits strong direct irritation to the skin and mucous membranes. This irritation can cause redness, swelling, pain, and burning sensation at the application site, affecting patient compliance, and may even damage the skin barrier function. Notably, even in its marketed injectable formulations, the vascular irritation of NCTD has been a clinical concern, further confirming its inherent irritant properties.

[0003] Therefore, one of the core challenges in developing NCTD topical formulations is how to effectively isolate or alleviate the direct contact irritation of the active pharmaceutical ingredient to the skin through advanced dosage form design, while promoting its penetration into the stratum corneum and increasing its retention in the targeted diseased skin layer (such as the epidermis) to achieve a local effective concentration and realize the goal of "reducing irritation and increasing efficacy". Summary of the Invention

[0004] The purpose of this invention is to provide a cantharidin latex, its preparation method, and its application. The cantharidin latex described in this invention exhibits high stability, uniform drug distribution, and low irritation. It can effectively isolate or alleviate the direct contact irritation of the raw drug to the skin, while simultaneously promoting its penetration into the stratum corneum and increasing its retention in the targeted lesion layer, achieving a locally effective concentration and realizing the goal of "reduced irritation and increased therapeutic effect."

[0005] This invention provides a demethylcantharidin latex, the raw materials for preparing the demethylcantharidin latex comprising the following components in parts by weight: 0.2-0.3 parts of demethylcantharidin, 2.0-3.0 parts of phospholipid, 0.5-0.75 parts of film stabilizer, 10-15 parts of oil phase matrix, 0.05-0.1 parts of co-emulsifier, 1.2-1.8 parts of emulsifier, 6.5-7.5 parts of gel matrix, 3.0-3.25 parts of humectant, and 950-1000 parts of water.

[0006] Preferably, the phospholipid is any one or more of egg yolk lecithin, soybean phospholipid, hydrogenated soybean phospholipid, and synthetic phospholipid; the synthetic phospholipid is dipalmitoylphosphatidylcholine or distearate phosphatidylcholine; the membrane stabilizer is cholesterol, cetyl alcohol, transoleyl alcohol, stigmasterol, or β-sitosterol; and the phospholipid, membrane stabilizer, and norcantharidin form a complex.

[0007] Preferably, the gel matrix is ​​any one or more of carbomer 940, carbomer 980, hydroxypropyl methylcellulose, methylcellulose, carboxymethylcellulose, carboxyethylcellulose, hydroxypropylcellulose, polyvinyl chloride, xanthan gum, guar gum, gum arabic, sodium alginate, chitosan, hyaluronic acid, polyethylene glycol monostearate, and poloxamer 407.

[0008] Preferably, the oil phase matrix is ​​a medium-chain triglyceride, ethyl oleate, liquid paraffin, silicone oil, or cocoyl decanoate.

[0009] Preferably, the emulsifier is any one or more of phosphatidylcholine, poloxamer, Tween 20, Tween 60, Span 20, Span 40, Span 80, propylene glycol monolaurate, and cetyl polyoxyethylene ether-20.

[0010] Preferably, the moisturizer is glycerin, propylene glycol, polyethylene glycol, or sorbitol.

[0011] Preferably, the co-emulsifier is oleic acid, linoleic acid, linolenic acid, stearic acid, hydroxypropyl methylcellulose stearoxy ether, sodium deoxycholate, or sodium diethyl succinate sulfonate.

[0012] In a specific embodiment, the pH value of the norcantharidin latex is 7.0~7.2.

[0013] This invention also provides a method for preparing the cantharidin latex described in the above technical solution, comprising the following steps: The gel matrix and water were mixed for the first time to obtain a blank gel; The phospholipids, membrane stabilizer, and norcantharidin were mixed a second time to obtain a complex; The oil phase matrix, the co-emulsifier, and the complex are mixed in a third step to obtain the oil phase. The emulsifier, humectant, and water are mixed in a fourth step to obtain the aqueous phase. The aqueous phase was added to the oil phase and emulsified under high pressure homogenization to obtain a norepinephrine emulsion. The norcantharidin emulsion and the blank gel are mixed for the fifth time to obtain norcantharidin emulsion.

[0014] The present invention also provides the application of the cantharidin latex preparation described in the above technical solution or the cantharidin latex preparation prepared by the preparation method described in the above technical solution in the preparation of a drug for treating viral skin warts; the viral skin warts include common warts, flat warts, plantar warts or condyloma acuminata.

[0015] This invention provides a demethylcantharidin latex. The demethylcantharidin latex is prepared using demethylcantharidin, phospholipids, membrane stabilizers, emulsifiers, oil phase matrix, co-emulsifiers, humectants, gel matrix, and water as raw materials. The demethylcantharidin latex of this invention has the following beneficial effects: (1) The demethylcantharidin latex prepared using demethylcantharidin, phospholipids, membrane stabilizers, emulsifiers, oil phase matrix, co-emulsifiers, humectants, gel matrix, and water as raw materials increases the skin retention of this latex. In the transdermal drug absorption experiment, the transdermal amount of demethylcantharidin within 8 hours is always below the detection limit of high performance liquid chromatography, i.e., the transdermal amount is less than 0.5 μg / cm³. 2 This indicates that the latex formulation of the present invention, through the encapsulation of phospholipid complex and the sustained-release effect of the gel matrix, allows norcantharidin to be mainly retained locally on the skin, with very little transdermal absorption into the systemic circulation, which can significantly reduce the risk of systemic toxicity. The drug retention amount of norcantharidin per unit area is 197.19 μg / cm². 2 The drug retention per unit area of ​​the same concentration of norcantharidin aqueous solution was 18.37 μg / cm². 2 For skin diseases such as condyloma acuminata, the drug needs to penetrate the stratum corneum and maintain an effective concentration in the basal layer of the epidermis and above. The increased retention of norepinephrine enhances its efficacy. (2) The latex preparation of the present invention has good safety. The skin irritation test results of the norepinephrine latex preparation prepared by the present invention show that the norepinephrine latex preparation has no obvious irritant effect on the skin of SD rats and has no sensitization. (3) The latex preparation prepared by the present invention has good stability. Centrifugal stability test, high temperature test, low temperature test, and freeze-thaw cycle test of the preparation of the present invention show that no layering, turbidity, color change, etc. were found. In the high temperature test of the influencing factor test, the drug content meets the established standard. In summary, the stability is good. (4) The norepinephrine latex preparation of the present invention is used to prepare a topical drug for skin warts related to viral infection. In the condyloma acuminata model experiment, the latex preparation showed a good clearance effect on the warts and had a low recurrence trend. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 Particle size distribution diagram of the norcantharidin emulsion provided by the present invention; Figure 2 Transmission electron microscopy image of the norepinephrine emulsion provided by the present invention; Figure 3 Microscopic images of the norcantharidin latex provided by the present invention. Detailed Implementation

[0018] This invention provides a demethylcantharidin latex, the raw materials for preparing the demethylcantharidin latex comprising the following components in parts by weight: 0.2-0.3 parts of demethylcantharidin, 2.0-3.0 parts of phospholipid, 0.5-0.75 parts of film stabilizer, 10-15 parts of oil phase matrix, 0.05-0.1 parts of co-emulsifier, 1.2-1.8 parts of emulsifier, 6.5-7.5 parts of gel matrix, 3.0-3.25 parts of humectant, and 950-1000 parts of water.

[0019] In a specific embodiment, norcantharidin, phospholipids, and a membrane stabilizer form a complex; the complex is mixed with an oil phase matrix and a co-emulsifier to obtain an oil phase; an emulsifier, a humectant, and water are used to prepare an aqueous phase; after preparing an emulsion from the aqueous and oil phases, the emulsion is mixed with a blank gel prepared from a gel matrix and water to prepare a latex. The norcantharidin latex of this invention effectively solves the problem of drug irritation to the skin. Its core mechanism lies in utilizing phospholipid complex technology. This invention tightly binds norcantharidin molecules with phospholipids and a membrane stabilizer to form a stable encapsulation structure. This structure encapsulates the originally highly irritating drug within a lipid core, greatly reducing the opportunity for direct contact between the drug and the skin, thus reducing irritation at the source. The complex is prepared as an oil phase, which is then mixed with the aqueous phase to form a stable emulsion. This emulsion is further mixed with a hydrophilic gel matrix to form the final latex. The gel matrix not only enhances the physical stability and adhesion of the formulation, making it easy to apply and forming a protective film on the skin surface, but also enables sustained drug release, avoiding irritation caused by a sudden increase in local drug concentration. Unlike existing commercially available cantharidin creams, the latex system of this invention effectively inhibits droplet aggregation and phase separation, significantly reducing the risk of demulsification, thinning, or damage to the honeycomb structure during long-term storage, thereby improving the problem of decreased stability of existing cantharidin creams under room temperature conditions. Compared with norcantharidin emulsion, which is an oil-water two-phase emulsion liquid where the oil and water phases are bound by an emulsifier, it is prone to stratification and demulsification during long-term room temperature storage. Through the above synergistic effect, this formulation successfully targets and retains norcantharidin locally on the skin lesion, enhancing local efficacy while significantly reducing drug irritation to normal skin tissue and the potential risk of systemic absorption, thus providing a safe and well-tolerated topical treatment option.

[0020] The present invention does not have any particular limitation on the source of norcantharidin, phospholipids, membrane stabilizers, oil phase matrix, co-emulsifiers, emulsifiers, gel matrix and moisturizers, and conventional commercially available products known to those skilled in the art can be used.

[0021] The cantharidin latex of this invention comprises 0.2-0.3 parts of cantharidin, which can be 0.2 parts, 0.22 parts, 0.24 parts, 0.25 parts, 0.26 parts, 0.28 parts, or 0.3 parts. Cantharidin is the main active ingredient in the latex of this invention, and it inhibits abnormal epidermal proliferation and promotes the necrosis and shedding of wart tissue. It achieves the effect of clearing warts by interfering with the cell proliferation process and inhibiting the growth of diseased tissue. As the core therapeutic ingredient, this invention, through the synergistic effect of the phospholipid complex structure and emulsification system, improves the retention and utilization efficiency of cantharidin on the skin, exerting a stable and continuous anti-wart effect.

[0022] The norcantharidin latex of this invention comprises 2.0-3.0 parts of phospholipids, which can be 2.5 parts, 2.75 parts, 2.6 parts, 2.8 parts, or 3 parts. In specific embodiments, the phospholipids are any one or more selected from egg yolk lecithin, soybean lecithin, hydrogenated soybean lecithin, and synthetic phospholipids; the synthetic phospholipids are dipalmitoylphosphatidylcholine or distearatelphosphatidylcholine. In this invention, the phospholipids function to form a complex system with norcantharidin and a membrane stabilizer, thereby improving the encapsulation efficiency and dispersion stability of the active ingredient at the emulsion droplet interface. The advantage of selecting any one or more of egg yolk lecithin, soybean lecithin, hydrogenated soybean lecithin, and synthetic phospholipids as phospholipids is that they possess good interfacial activity, biocompatibility, and stability, which is beneficial for forming a dense and stable emulsion droplet interface structure, thus improving the safety and storage stability of the formulation.

[0023] The norcantharidin latex of this invention includes 0.5 to 0.75 parts of a membrane stabilizer, which can be 0.5 parts, 0.55 parts, 0.6 parts, 0.625 parts, 0.65 parts, 0.68 parts, 0.7 parts, or 0.75 parts. In specific embodiments, the membrane stabilizer is cholesterol, cetyl alcohol, trans-oleol, stigmasterol, or β-sitosterol. In this invention, the membrane stabilizer functions to form a complex system with norcantharidin and phospholipids, promoting the stable encapsulation of the active ingredient and obtaining a stable complex. The advantage of choosing cholesterol, cetyl alcohol, trans-oleol, stigmasterol, or β-sitosterol as a membrane stabilizer is that it can synergistically construct a stable interfacial membrane structure with phospholipids, improving the physical stability of the latex system.

[0024] The norcantharidin latex of this invention comprises 10-15 parts of an oil phase matrix, which can be 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, or 15 parts. In specific embodiments, the oil phase matrix is ​​a medium-chain triglyceride, ethyl oleate, liquid paraffin, silicone oil, or cocoyl caprylate. In this invention, the function of the oil phase matrix is ​​to provide a dissolution environment and help stabilize the interface during the emulsification process, thereby improving emulsion stability and drug encapsulation efficiency. The advantages of choosing medium-chain triglycerides, ethyl oleate, liquid paraffin, silicone oil, or cocoyl caprylate as the oil phase matrix are excellent solubility, low toxicity, and high stability, which can ensure the long-term stability and effectiveness of the emulsion system.

[0025] The cantharidin latex of this invention includes 0.05-0.1 parts of a co-emulsifier, which can be 0.05 parts, 0.06 parts, 0.065 parts, 0.07 parts, 0.075 parts, 0.08 parts, 0.085 parts, 0.09 parts, 0.095 parts, or 0.1 parts. In specific embodiments, the co-emulsifier is oleic acid, linoleic acid, linolenic acid, stearic acid, hydroxypropyl methylcellulose stearoxy ether, sodium deoxycholate, or sodium diethyl succinate sulfonate. In specific embodiments, the hydroxypropyl methylcellulose stearoxy ether includes SANGELOSE 90L or SANGELOSE 60L. In this invention, the co-emulsifier functions to reduce the oil-water interfacial tension, enhance emulsion stability, and promote the encapsulation and sustained release of active ingredients. The advantages of choosing oleic acid, linoleic acid, linolenic acid, stearic acid, hydroxypropyl methylcellulose stearyl ether, sodium deoxycholate, or sodium diethyl succinate sulfonate as co-emulsifiers are good interfacial activity and biocompatibility, which can effectively improve emulsification efficiency, enhance droplet stability, and prevent stratification.

[0026] The cantharidin latex of this invention comprises 1.2 to 1.8 parts of emulsifier, which can be 1.2 parts, 1.25 parts, 1.3 parts, 1.35 parts, 1.4 parts, 1.5 parts, 1.6 parts, 1.65 parts, 1.7 parts, or 1.8 parts. In specific embodiments, the emulsifier is any one or more of phosphatidylcholine, poloxamer, Tween 20, Tween 60, Span 20, Span 40, Span 80, propylene glycol monolaurate, and cetyl polyoxyethylene ether-20. In this invention, the function of the emulsifier is to reduce the interfacial tension between the oil and water phases and promote the stable bonding of the oil and water phases. The advantages of using one or more of the following emulsifiers as emulsifiers are good interfacial activity, high biocompatibility, strong emulsifying effect and improved long-term stability of emulsion.

[0027] The cantharidin latex of this invention comprises 6.5 to 7.5 parts of a gel matrix, which can be 6.5, 6.6, 6.8, 7, 7.2, 7.4, or 7.5 parts. In specific embodiments, the gel matrix is ​​any one or more of carbomer 940, carbomer 980, hydroxypropyl methylcellulose, methylcellulose, carboxymethylcellulose, carboxyethylcellulose, hydroxypropylcellulose, polyvinyl carboxylate, xanthan gum, guar gum, gum arabic, sodium alginate, chitosan, hyaluronic acid, polyethylene glycol monostearate, and poloxamer 407. In this invention, the gel matrix acts as a carrier for the formulation, providing suitable physical states and viscosity to ensure the stability of the emulsion or gel. Choosing one or more of the following as a gel matrix offers advantages such as good thickening properties, emulsification stability, and biocompatibility, and can improve the stability and skin permeability of the formulation: Carbomer 940, Carbomer 980, hydroxypropyl methylcellulose, methylcellulose, carboxymethylcellulose, carboxyethylcellulose, hydroxypropylcellulose, polyvinyl chloride, xanthan gum, guar gum, gum arabic, sodium alginate, chitosan, hyaluronic acid, polyethylene glycol monostearate, and poloxamer 407.

[0028] The cantharidin latex of this invention includes 3.0 to 3.25 parts of a moisturizer, which can be 3.1 parts, 3.125 parts, 3.18 parts, 3.2 parts, 3.22 parts, or 3.25 parts. In specific embodiments, the moisturizer is glycerin, propylene glycol, polyethylene glycol, or sorbitol. In this invention, the moisturizer functions to retain moisture on the skin surface through hygroscopic action, enhancing skin hydration and preventing dryness. The advantages of choosing glycerin, propylene glycol, polyethylene glycol, or sorbitol as a moisturizer are strong hygroscopicity, good skin permeability, and low irritation, effectively improving skin hydration.

[0029] The cantharidin latex of this invention comprises 950-1000 parts of water, which can be 950 parts, 970 parts, 972 parts, 974 parts, 975 parts, or 990 parts. In a specific embodiment, the water can be purified water.

[0030] In a specific embodiment, the pH value of the norcantharidin latex is 7.0-7.2. In a specific embodiment, the pH adjuster is sodium hydroxide, diethylamine, or triethanolamine. The advantage of choosing sodium hydroxide, diethylamine, or triethanolamine as the pH adjuster in this invention is its ability to regulate pH, ensuring that the pH value of the formulation is within a suitable range for the skin (7.0-7.2), avoiding irritation, and helping to maintain the long-term stability of the formulation.

[0031] The core mechanism of this invention's norcantharidin emulsion lies in the utilization of phospholipid complex technology. Norcantharidin molecules are tightly bound with phospholipids and membrane stabilizers to form a stable encapsulation structure. This structure encapsulates the normally highly irritating drug within a lipid core, significantly reducing the chance of direct contact between the drug and the skin, thus minimizing irritation at the source. Each excipient plays a unique role; the absence of any excipient may lead to a decrease in the formulation's efficacy. Phospholipids effectively improve the encapsulation efficiency of norcantharidin and promote stable retention of the drug at the local skin lesion. Removing phospholipids reduces the stability of the emulsion, significantly weakening the local drug retention effect and thus affecting the therapeutic outcome. The membrane stabilizer works synergistically with phospholipids to stabilize the droplet structure; without a membrane stabilizer, the emulsion is prone to stratification, affecting the stability of the formulation.

[0032] The oil phase matrix provides a favorable dissolution environment, aiding in interfacial stability during emulsification. The selection of the oil phase matrix in this invention promotes uniform drug dispersion and improves its encapsulation effect; however, an inappropriate selection may reduce the drug's solubility in the oil phase, thus affecting the emulsification effect. The emulsifier forms a stable film at the oil-water interface, ensuring good bonding between the emulsion and oil phases. Choosing a suitable emulsifier is crucial for ensuring emulsion stability and effectiveness. Without an emulsifier, the emulsion may fail to form stable droplets, resulting in poor post-use efficacy. The moisturizer retains moisture on the skin surface through hygroscopic action, enhancing skin hydration and preventing dryness. Removing the moisturizer may lead to skin dryness due to moisture loss, affecting comfort. Sodium hydroxide, diethylamine, or triethanolamine act as pH adjusters, ensuring the latex's pH is controlled between 7.0 and 7.2, avoiding skin irritation. Without a pH adjuster, the emulsion's pH may deviate from the skin's optimal range, causing skin irritation.

[0033] This invention also provides a method for preparing the cantharidin latex described in the above technical solution, comprising the following steps: The gel matrix and water were mixed for the first time to obtain a blank gel; The phospholipids, membrane stabilizer, and norcantharidin were mixed a second time to obtain a complex; The oil phase matrix, the co-emulsifier, and the complex are mixed in a third step to obtain the oil phase. The emulsifier, humectant, and water are mixed in a fourth step to obtain the aqueous phase. The aqueous phase was added to the oil phase and emulsified under high pressure homogenization to obtain a norepinephrine emulsion. The norcantharidin emulsion and the blank gel are mixed for the fifth time to obtain norcantharidin emulsion.

[0034] This invention involves a first mixing of a gel matrix and water to obtain a blank gel. In a specific embodiment, the water includes purified water. The invention further involves mixing the gel matrix and water, dispersing them evenly, and allowing them to swell sufficiently to obtain a blank gel. In a specific embodiment, the weight percentage of water mixed with the gel matrix can be 830-920 parts, used for dispersing and swelling the gel matrix. In a specific embodiment, the swelling time can be 8-14 hours, specifically 12 hours.

[0035] This invention involves a second mixing of phospholipids, a membrane stabilizer, and norcantharidin to obtain a complex. In a specific embodiment, the temperature of the second mixing is 35-45°C. This invention achieves this temperature by heating. The invention uses an organic solvent to dissolve norcantharidin, phospholipids, and the membrane stabilizer before the second mixing. In a specific embodiment, the second mixing is carried out under a nitrogen atmosphere. The nitrogen atmosphere is pure nitrogen at atmospheric pressure; its function is to reduce the reaction of oxygen and moisture with the components in the formulation, ensuring the stability of the preparation. This invention can use an organic solvent that promotes the formation of the complex from norcantharidin, phospholipids, and the membrane stabilizer. In a specific embodiment, the organic solvent is removed by rotary evaporation under reduced pressure after the complex is formed and does not enter the final formulation. In a specific embodiment, the organic solvent can be anhydrous ethanol, isopropanol, or ethyl acetate. In a specific embodiment, based on 0.2-0.3 parts by weight of norcantharidin, the organic solvent is 12-18 parts by weight. When organic solvents are used to dissolve phospholipids and membrane stabilizers, and when organic solvents are used to dissolve norcantharidin, the weight parts of the organic solvent used to dissolve the phospholipids and membrane stabilizers are 8-12 parts, and the weight parts of the organic solvent used to dissolve norcantharidin can be 4-6 parts. In a specific embodiment, the phospholipids and membrane stabilizers are mixed with anhydrous ethanol, and the mixture is stirred at 35-45°C until a clear solution is obtained. Then, norcantharidin dissolved in anhydrous ethanol is added, and the mixture is stirred again at 35-45°C. In a specific embodiment, the stirring rates of the first and second stirring are 50-300 r / min, and can be 100 r / min. In a specific embodiment, the stirring time of the first stirring is 0.3-0.7 h, and can be 0.5 h. In a specific embodiment, the stirring time of the second stirring is 3-5 h, and can be 4 h.

[0036] After obtaining the composite, the present invention performs a third mixing of the oil phase matrix, the co-emulsifier, and the composite to obtain the oil phase. In a specific embodiment, the temperature of the third mixing is 35~45℃, which can be 35℃, 40℃, or 45℃. In a specific embodiment, the third mixing is carried out under a nitrogen atmosphere. In a specific embodiment, the third mixing is stirred until the solution is clear.

[0037] This invention involves a fourth mixing of an emulsifier, a humectant, and water to obtain an aqueous phase. In a specific embodiment, the water in the fourth mixing comprises 80-120 parts by weight, used to prepare the aqueous phase required for emulsification. In a specific embodiment, the fourth mixing is performed by shearing at a speed of 3000-5000 rpm (4000 rpm) for a time of 1-2 minutes (1 minute). Within the above range, the shearing time can be appropriately increased when the speed is low.

[0038] After obtaining the aqueous and oil phases, this invention adds the aqueous phase to the oil phase and emulsifies under high pressure to obtain a norcantharidin emulsion. This invention rapidly adds the aqueous phase to the oil phase. In a specific embodiment, premixing is performed before emulsification using high-pressure homogenization to ensure the oil phase is uniformly dispersed in the aqueous phase. In a specific embodiment, the premixing conditions can be shearing at 10000 rpm for 1.5 min. In a specific embodiment, the high-pressure homogenization conditions can be: pre-homogenization (0 bar) followed by a multi-stage homogenization process with progressively increasing pressures of 100 bar, 300 bar, 500 bar, and 800 bar, with each pressure level being homogenized three times consecutively, and the temperature during homogenization being 20°C. Using a high-pressure homogenization emulsification process ensures that the resulting droplets are small in size and uniformly distributed, ensuring thorough emulsification of the oil and aqueous phases to form a stable emulsion.

[0039] After obtaining the norcantharidin emulsion and the blank gel, the present invention performs a fifth mixing of the norcantharidin emulsion and the blank gel to obtain a norcantharidin latex. In a specific embodiment, the temperature of the fifth mixing is 20~30℃. In a specific embodiment, the fifth mixing can be stirring to ensure uniform dispersion of the system. After the system is uniformly dispersed, the present invention adjusts the pH value to 7.0~7.2. In a specific embodiment, the pH adjusting agent can be sodium hydroxide, diethylamine, or triethanolamine.

[0040] This invention utilizes processes such as phospholipid complex preparation, hydrogel dispersion, and emulsification to produce a latex with good stability, uniform particle size, uniform drug distribution, and increased skin retention. In drug retention experiments, the drug retention per unit area of ​​the same concentration of norcantharidin aqueous solution was 18.37 μg / cm². 2 The amount of norcantharidin retained per unit area in the latex was 197.19 μg / cm². 2The skin retention of the latex is significantly higher than that of the same concentration of norcantharidin aqueous solution. Compared with the control group without phospholipids and emulsified by ordinary mechanical stirring, the latex of this invention has a smaller particle size, more uniform distribution, and greater stability. When a high-pressure homogenization process is not used or phospholipid components are lacking, the energy provided during emulsification is insufficient or a stable interfacial structure is difficult to form, resulting in limited droplet refinement, a wider particle size distribution, a significantly larger particle size, and a decrease in the stability and skin retention performance of the latex system.

[0041] The present invention also provides the application of the cantharidin latex preparation described in the above technical solution or the cantharidin latex preparation prepared by the preparation method described in the above technical solution in the preparation of a drug for treating viral skin warts; the viral skin warts include common warts, flat warts, plantar warts or condyloma acuminata.

[0042] To further illustrate the present invention, the following detailed description, in conjunction with embodiments, of a cantharidin latex agent, its preparation method, and its application, is provided by the present invention, but these descriptions should not be construed as limiting the scope of protection of the present invention.

[0043] Example 1 A method for preparing a cantharidin latex includes the following steps: Weigh out 0.25g of norcantharidin, 2.5g of phospholipid (egg yolk lecithin E80), 0.625g of membrane stabilizer (cholesterol), 12.5g of oil phase matrix (medium-chain triglycerides), 0.075g of co-emulsifier (oleic acid), 1.5g of emulsifier (soybean lecithin 80), 7g of gel matrix (carbomer 980), 3.125g of humectant (glycerin), and 972g of purified water; Add 872g of purified water to 7g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain blank gel; 2.5 g of phospholipid, 0.625 g of film stabilizer, and 10 g of anhydrous ethanol were mixed and heated to 40 °C under nitrogen atmosphere and stirred for 0.5 h until a clear solution was obtained. 0.25 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 40 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 40 °C, a complex was obtained. 12.5 g of oil phase matrix and 0.075 g of co-emulsifier were mixed with the complex and heated and stirred under nitrogen atmosphere at 40 °C for 0.5 h until a clear solution was obtained, yielding the oil phase. 1.5 g of emulsifier and 3.125 g of humectant were added to 100 g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 40 °C until a clear solution was obtained, yielding the aqueous phase. The aqueous phase was rapidly added to the oil phase, and 10000... Shear at rpm for 1.5 min, pre-homogenize once at 0 bar using high pressure homogenizer, and then perform stepwise pressure-increasing homogenization at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise pressure-increasing homogenization is to homogenize twice at each set pressure and then increase to the next pressure for homogenization. The temperature during the homogenization process is 20℃, to obtain the norcantharidin emulsion. The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.0 with triethanolamine to obtain the norcantharidin emulsion.

[0044] The particle size distribution, microstructure, and dispersion state of the norcantharidin emulsion and latex prepared in Example 1 were observed, and the results are shown in the figures below. Figures 1-3 .in, Figure 1 This is a particle size distribution diagram of the norcantharidin emulsion obtained in Example 1; Figure 2 This is a transmission electron microscope image of the norcantharidin emulsion obtained in Example 1; Figure 3 This is a microscopic image of the norcantharidin latex obtained in Example 1.

[0045] Depend on Figure 1 It can be seen that the norepinephrine emulsion prepared in Example 1 has a concentrated particle size distribution, a small average particle size, and a narrow distribution curve, indicating that the droplet particle size is significantly refined after stepwise high-pressure homogenization and the system has good uniformity.

[0046] Depend on Figure 2 As can be seen, the droplets are regular in shape and distributed in a near-spherical manner, with no obvious aggregation or fusion phenomenon, which further indicates that the composite structure formed by phospholipids and membrane stabilizers can effectively stabilize the droplet interface.

[0047] Depend on Figure 3 As can be seen, after mixing with the blank gel to form a latex, the latex droplets are still uniformly dispersed in the gel network structure, without obvious stratification or aggregation, indicating that the latex system of the present invention has good physical stability.

[0048] The above results demonstrate that the present invention, through a phospholipid-film stabilizer composite system combined with a stepwise high-pressure homogenization process, can obtain a norepinephrine latex system with small particle size, uniform distribution, and stable structure.

[0049] Example 2 A method for preparing a cantharidin latex includes the following steps: Weigh out the following components by weight: 0.25g of norcantharidin, 2.75g of phospholipid (hydrogenated soybean phospholipid HSPC), 0.625g of membrane stabilizer (cholesterol), 12.5g of oil phase matrix (medium-chain triglycerides), 0.075g of co-emulsifier (oleic acid), 1.5g of emulsifier (soybean phospholipid 70), 7g of gel matrix (carbomer 980), 3.125g of humectant (glycerol), and 972g of purified water. Add 872g of purified water to 7g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain blank gel; 2.75 g of phospholipid, 0.625 g of film stabilizer, and 10 g of anhydrous ethanol were mixed and heated to 35 °C under nitrogen atmosphere and stirred for 0.5 h until a clear solution was obtained. 0.25 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 35 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 35 °C, a complex was obtained. 12.5 g of oil phase matrix and 0.075 g of co-emulsifier were mixed with the complex and heated and stirred under nitrogen atmosphere at 35 °C for 0.5 h until a clear solution was obtained, yielding the oil phase. 1.5 g of emulsifier and 3.125 g of humectant were added to 100 g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 35 °C until a clear solution was obtained, yielding the aqueous phase. The aqueous phase was rapidly added to the oil phase, and 10000... Shear at rpm for 1.5 min, pre-homogenize once at 0 bar using high pressure homogenizer, and then perform stepwise pressure-increasing homogenization at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise pressure-increasing homogenization is to homogenize three times at each set pressure before increasing to the next pressure for homogenization. The temperature during homogenization is 20℃, to obtain the norcantharidin emulsion. The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.0 with triethanolamine to obtain the norcantharidin emulsion.

[0050] Example 3 A method for preparing a cantharidin latex includes the following steps: Weigh out the following ingredients by weight percentage: 0.25g of norcantharidin, 2.5g of phospholipid (egg yolk lecithin E80), 0.75g of membrane stabilizer (cholesterol), 15g of oil phase matrix (ethyl oleate), 0.075g of co-emulsifier (stearic acid), 1.5g of emulsifier (soybean lecithin 80), 7g of gel matrix (carbomer 940), 3.125g of humectant (glycerin), and 970g of purified water. Add 890g of purified water to 7g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain blank gel; 2.5 g of phospholipid, 0.75 g of film stabilizer, and 10 g of anhydrous ethanol were mixed and heated to 45 °C under nitrogen atmosphere and stirred for 0.5 h until a clear solution was obtained. 0.25 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 45 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 45 °C, a complex was obtained. 15 g of oil phase matrix, 0.075 g of co-emulsifier, and the complex were mixed and heated and stirred under nitrogen atmosphere at 45 °C for 0.5 h until a clear solution was obtained, yielding the oil phase. 1.5 g of emulsifier and 3.125 g of humectant were added to 80 g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 45 °C until a clear solution was obtained, yielding the aqueous phase. The aqueous phase was quickly added to the oil phase, and 10000... Shear at rpm for 1.5 min, pre-homogenize once at 0 bar using high pressure homogenizer, and then perform stepwise pressure-increasing homogenization at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise pressure-increasing homogenization is to homogenize three times at each set pressure before increasing to the next pressure for homogenization. The temperature during homogenization is 20℃, to obtain the norcantharidin emulsion. The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.0 with sodium hydroxide to obtain the norcantharidin emulsion.

[0051] Example 4 A method for preparing a cantharidin latex includes the following steps: Weigh out the following ingredients by weight percentage: 0.2g of norcantharidin, 3g of phospholipid (dipalmitoylphosphatidylcholine DPPC), 0.5g of membrane stabilizer (cholesterol), 15g of oil phase matrix (ethyl oleate), 0.06g of co-emulsifier (SANGELOSE 90L), 1.25g of emulsifier (soybean lecithin 80), 7g of gel matrix (carbomer 980), 3.125g of humectant (glycerin), and 970g of purified water. Add 890g of purified water to 7g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain blank gel; 3g of phospholipid, 0.5g of film stabilizer, and 8g of anhydrous ethanol were mixed and heated to 40°C under nitrogen atmosphere with stirring for 0.5h until a clear solution was obtained. 0.2g of norcantharidin (pre-dissolved in 4g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 40°C for 4h. After removing the anhydrous ethanol by rotary evaporation under heating at 40°C, a complex was obtained. 15g of oil phase matrix, 0.06g of co-emulsifier, and the complex were mixed and heated and stirred under nitrogen atmosphere at 40°C for 0.5h until a clear solution was obtained, yielding the oil phase. 1.25g of emulsifier and 3.125g of humectant were added to 80g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 40°C until a clear solution was obtained, yielding the aqueous phase. The aqueous phase was rapidly added to the oil phase, and 10000... Shear at rpm for 1.5 min, pre-homogenize once at 0 bar using high pressure homogenizer, and then perform stepwise pressure-increasing homogenization at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise pressure-increasing homogenization is to homogenize three times at each set pressure before increasing to the next pressure for homogenization. The temperature during homogenization is 20℃, to obtain the norcantharidin emulsion. The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.2 with sodium hydroxide to obtain the norcantharidin emulsion.

[0052] Example 5 A method for preparing a cantharidin latex includes the following steps: Weigh out the following components by weight: 0.3g of norcantharidin, 3g of phospholipid (distearylphosphatidylcholine DSPC), 0.75g of membrane stabilizer (cholesterol), 15g of oil phase matrix (medium-chain triglycerides), 0.1g of co-emulsifier (linolenic acid), 1.8g of emulsifier (soybean lecithin 80), 7g of gel matrix (carbomer 980), 3.125g of humectant (glycerin), and 970g of purified water. Add 850g of purified water to 7g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain blank gel; 3g of phospholipid, 0.75g of film stabilizer, and 12g of anhydrous ethanol were mixed and heated to 40°C under nitrogen atmosphere and stirred for 0.5h until a clear solution was obtained. 0.3g of norcantharidin (pre-dissolved in 6g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 40°C for 4h. After removing the anhydrous ethanol by rotary evaporation under heating at 40°C, a complex was obtained. 15g of oil phase matrix, 0.1g of co-emulsifier, and the complex were mixed and heated and stirred under nitrogen atmosphere at 40°C for 0.5h until a clear solution was obtained, yielding the oil phase. 1.8g of emulsifier and 3.125g of humectant were added to 120g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 40°C until a clear solution was obtained, yielding the aqueous phase. The aqueous phase was rapidly added to the oil phase, and 10000... Shear at rpm for 1.5 min, pre-homogenize once at 0 bar using high pressure homogenizer, and then perform stepwise pressure-increasing homogenization at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise pressure-increasing homogenization is to homogenize three times at each set pressure before increasing to the next pressure for homogenization. The temperature during homogenization is 25℃, to obtain the norcantharidin emulsion. The norcantharidin emulsion and blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.2 with diethylamine to obtain norcantharidin emulsion.

[0053] Example 6 A method for preparing a cantharidin latex includes the following steps: Weigh out the following ingredients by weight percentage: 0.25g of norcantharidin, 2.5g of phospholipid (egg yolk lecithin E80), 0.5g of membrane stabilizer (cholesterol), 10g of oil phase matrix (medium-chain triglycerides), 0.05g of co-emulsifier (SANGELOSE 90L), 1.8g of emulsifier (Tween 20), 7g of gel matrix (carbomer 980), 3g of humectant (glycerin), and 975g of purified water. Add 895g of purified water to 7g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain blank gel; 2.5 g of phospholipid, 0.5 g of film stabilizer, and 10 g of anhydrous ethanol were mixed and heated to 35 °C under nitrogen atmosphere with stirring for 0.5 h until a clear solution was obtained. 0.25 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 35 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 35 °C, the complex was obtained. 10 g of oil phase matrix, 0.05 g of co-emulsifier, and the complex were mixed and heated and stirred under nitrogen atmosphere at 35 °C for 0.5 h until the solution was clear, obtaining the oil phase. 1.8 g of emulsifier and 3 g of humectant were added to 80 g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 35 °C until the solution was clear, obtaining the aqueous phase. The aqueous phase was quickly added to the oil phase. Shear at rpm for 1.5 min, pre-homogenize once at 0 bar using high pressure homogenizer, and then perform stepwise pressure-increasing homogenization at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise pressure-increasing homogenization is to homogenize three times at each set pressure before increasing to the next pressure for homogenization. The temperature during homogenization is 25℃, to obtain the norcantharidin emulsion. The norcantharidin emulsion and blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.2 with diethylamine to obtain norcantharidin emulsion.

[0054] Example 7 A method for preparing a cantharidin latex includes the following steps: Weigh out the following ingredients by weight percentage: 0.25g of norcantharidin, 2.5g of phospholipid (soybean phospholipid S75), 0.6g of film stabilizer (stigmasterol), 13g of oil phase matrix (liquid paraffin), 0.08g of co-emulsifier (linoleic acid), 1.4g of emulsifier (poloxam 188), 6.8g of gel matrix (hydroxypropyl methylcellulose K4M), 3.1g of humectant (propylene glycol), and 972g of purified water. Add 872g of purified water to 6.8g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain a blank gel; 2.5 g of phospholipid, 0.6 g of film stabilizer, and 10 g of anhydrous ethanol were mixed and heated to 45 °C under nitrogen atmosphere with stirring for 0.5 h until a clear solution was obtained. 0.25 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 45 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 45 °C, the complex was obtained. 13 g of oil phase matrix, 0.08 g of co-emulsifier, and the complex were mixed and heated and stirred under nitrogen atmosphere at 45 °C for 0.5 h until a clear solution was obtained, yielding the oil phase. 1.4 g of emulsifier and 3.1 g of humectant were added to 100 g of purified water, and the mixture was sheared at 4000 rpm at 45 °C for 1 hour. The solution was kept clear until the aqueous phase was obtained. The aqueous phase was quickly added to the oil phase and sheared at 10,000 rpm for 1.5 min. The solution was then pre-homogenized once at 0 bar using high pressure homogenization. The homogenization was then performed stepwise at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise homogenization was performed by homogenizing three times at each set pressure before increasing to the next pressure for homogenization. The temperature during the homogenization process was 25°C, resulting in a norepinephrine emulsion. The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.1 with triethanolamine to obtain the norcantharidin emulsion.

[0055] Example 8 A method for preparing a cantharidin latex includes the following steps: Weigh out the following ingredients by weight percentage: 0.22g of norcantharidin, 2.8g of phospholipid (hydrogenated soybean phospholipid HSPC-98), 0.7g of membrane stabilizer (β-sitosterol), 11g of oil phase matrix (silicone oil DC200), 0.09g of co-emulsifier (sodium deoxycholate), 1.3g of emulsifier (a 1:1 mixture of Span 60 and Tween 60), 7.2g of gel matrix (methylcellulose MC4000), 3.05g of humectant (polyethylene glycol 400), and 974g of purified water. Add 884g of purified water to 7.2g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain a blank gel; 2.8 g of phospholipid, 0.7 g of film stabilizer, and 9 g of anhydrous ethanol were mixed and heated to 35 °C under nitrogen atmosphere and stirred for 0.5 h until a clear solution was obtained. 0.22 g of norcantharidin (pre-dissolved in 4 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 35 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 35 °C, the complex was obtained. 11 g of oil phase matrix, 0.09 g of co-emulsifier, and the complex were mixed and heated and stirred under nitrogen atmosphere at 35 °C for 0.5 h until a clear solution was obtained, yielding the oil phase. 1.3 g of emulsifier and 3.05 g of humectant were added to 90 g of purified water, and the mixture was sheared at 4000 rpm at 35 °C for 1 hour. The solution was kept clear until the aqueous phase was obtained. The aqueous phase was quickly added to the oil phase and sheared at 10,000 rpm for 1.5 min. The solution was then pre-homogenized once at 0 bar using a high-pressure homogenizer. The homogenization was then performed stepwise at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise homogenization was performed by homogenizing three times at each set pressure before increasing to the next pressure. The temperature during the homogenization process was 20°C, resulting in a norepinephrine emulsion. The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.0 with triethanolamine to obtain the norcantharidin emulsion.

[0056] Example 9 A method for preparing a cantharidin latex includes the following steps: Weigh out the following components by weight percentage: 0.28g of norcantharidin, 2.3g of phospholipid (dipalmitoylphosphatidylcholine DPPC), 0.55g of membrane stabilizer (cetyl alcohol), 14g of oil phase matrix (cocoyl decanoate), 0.06g of co-emulsifier (sodium diethyl succinate), 1.6g of emulsifier (cetyl polyoxyethylene ether-20), 6.6g of gel matrix (sodium carboxymethyl cellulose 990), 3.2g of humectant (sorbitol), and 971g of purified water. Add 861g of purified water to 6.6g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain blank gel; 2.3 g of phospholipid, 0.55 g of film stabilizer, and 11 g of anhydrous ethanol were mixed and heated to 40 °C under nitrogen atmosphere and stirred for 0.5 h until a clear solution was obtained. 0.28 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 40 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 40 °C, a complex was obtained. 14 g of oil phase matrix, 0.06 g of co-emulsifier, and the complex were mixed and heated and stirred under nitrogen atmosphere at 40 °C for 0.5 h until a clear solution was obtained, yielding the oil phase. 1.6 g of emulsifier and 3.2 g of humectant were added to 110 g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 40 °C until a clear solution was obtained, yielding the aqueous phase. The aqueous phase was rapidly added to the oil phase, and 10000... Shear at rpm for 1.5 min, pre-homogenize once at 0 bar using high pressure homogenizer, and then perform stepwise pressure-increasing homogenization at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise pressure-increasing homogenization is to homogenize three times at each set pressure before increasing to the next pressure for homogenization. The temperature during homogenization is 20℃, to obtain the norcantharidin emulsion. The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.2 with triethanolamine to obtain the norcantharidin emulsion.

[0057] Example 10 A method for preparing a cantharidin latex includes the following steps: Weigh out the following components by weight: 0.26 g of norcantharidin, 2.4 g of phospholipid (distearylphosphatidylcholine DSPC), 0.65 g of membrane stabilizer (transoleyl alcohol), 12 g of oil phase matrix (ethyl oleate), 0.07 g of co-emulsifier (stearic acid), 1.8 g of emulsifier (propylene glycol monolaurate and Span 80 mixed in a 2:1 ratio), 7.4 g of gel matrix (carboxyethyl cellulose), 3.15 g of humectant (glycerin and propylene glycol mixed in a 1:1 ratio), and 972 g of purified water. Add 862g of purified water to 7.4g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain a blank gel; 2.4 g of phospholipid, 0.65 g of film stabilizer, and 9 g of anhydrous ethanol were mixed and heated to 40 °C under nitrogen atmosphere with stirring for 0.5 h until a clear solution was obtained. 0.26 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 40 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 40 °C, the complex was obtained. 12 g of oil phase matrix, 0.07 g of co-emulsifier, and the complex were mixed and heated and stirred under nitrogen atmosphere at 40 °C for 0.5 h until a clear solution was obtained, yielding the oil phase. 1.8 g of emulsifier and 3.15 g of humectant were added to 110 g of purified water, and the mixture was sheared at 4000 rpm at 40 °C for 1 hour. The solution was kept clear until the aqueous phase was obtained. The aqueous phase was quickly added to the oil phase and sheared at 10,000 rpm for 1.5 min. The solution was then pre-homogenized once at 0 bar using a high-pressure homogenizer. The homogenization was then performed stepwise at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise homogenization was performed by homogenizing three times at each set pressure before increasing to the next pressure. The temperature during the homogenization process was 20°C, resulting in a norepinephrine emulsion. The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.1 with triethanolamine to obtain the norcantharidin emulsion.

[0058] Example 11 A method for preparing a cantharidin latex includes the following steps: Weigh out the following components by weight: 0.27g of norcantharidin, 2.7g of phospholipids (soybean phospholipid SPC-80), 0.68g of film stabilizer (cholesterol), 13.5g of oil phase matrix (medium-chain triglycerides), 0.085g of co-emulsifier (linolenic acid), 1.55g of emulsifier (a mixture of poloxamer 407 and phosphatidylcholine PC-98 in a 3:2 ratio), 6.9g of gel matrix (hydroxypropyl methylcellulose K15M), 3.18g of humectant (a mixture of polyethylene glycol 600 and glycerin in a 2:3 ratio), and 971g of purified water. Add 871g of purified water to 6.9g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain a blank gel; 2.7 g of phospholipid, 0.68 g of film stabilizer, and 11 g of anhydrous ethanol were mixed and heated to 40 °C under nitrogen atmosphere and stirred for 0.5 h until a clear solution was obtained. 0.27 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 40 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 40 °C, a complex was obtained. 13.5 g of oil phase matrix and 0.085 g of co-emulsifier were mixed with the complex and heated and stirred under nitrogen atmosphere at 40 °C for 0.5 h until a clear solution was obtained, yielding the oil phase. 1.55 g of emulsifier and 3.18 g of humectant were added to 100 g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 40 °C until a clear solution was obtained, yielding the aqueous phase. The aqueous phase was rapidly added to the oil phase, and 10000... Shear at rpm for 1.5 min, pre-homogenize once at 0 bar using high pressure homogenizer, and then perform stepwise pressure-increasing homogenization at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise pressure-increasing homogenization is to homogenize three times at each set pressure before increasing to the next pressure for homogenization. The temperature during homogenization is 20℃, to obtain the norcantharidin emulsion. The norcantharidin emulsion and blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.15 with triethanolamine to obtain norcantharidin emulsion.

[0059] Comparative Example 1 Except for the absence of phospholipids, the types and amounts of other raw materials and the preparation methods are the same as in Example 1.

[0060] A method for preparing a cantharidin latex includes the following steps: Weigh out 0.25g of norcantharidin, 0.625g of membrane stabilizer (cholesterol), 12.5g of oil phase matrix (medium-chain triglycerides), 0.075g of co-emulsifier (oleic acid), 1.5g of emulsifier (soybean lecithin 80), 7g of gel matrix (carbomer 980), 3.125g of humectant (glycerin), and 972g of purified water by weight percentage. Add 872g of purified water to 7g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain blank gel; 0.625 g of film stabilizer and 10 g of anhydrous ethanol were mixed and heated to 40 °C under nitrogen atmosphere and stirred for 0.5 h until a clear solution was obtained. 0.25 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 40 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 40 °C, the complex was obtained. 12.5 g of oil phase matrix and 0.075 g of co-emulsifier were mixed with the complex and heated and stirred under nitrogen atmosphere at 40 °C for 0.5 h until the solution was clear, obtaining the oil phase. 1.5 g of emulsifier and 3.125 g of humectant were added to 100 g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 40 °C until the solution was clear, obtaining the aqueous phase. The aqueous phase was quickly added to the oil phase. Shear at rpm for 1.5 min, pre-homogenize once at 0 bar using high pressure homogenizer, and then perform stepwise pressure-increasing homogenization at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise pressure-increasing homogenization is to homogenize three times at each set pressure before increasing to the next pressure for homogenization. The temperature during homogenization is 20℃, to obtain the norcantharidin emulsion. The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.0 with triethanolamine to obtain the norcantharidin emulsion.

[0061] Comparative Example 2 The amount of norcantharidin was adjusted to be lower than the range defined in the claims, and the types and amounts of the other raw materials and the preparation methods were the same as in Example 1.

[0062] A method for preparing a cantharidin latex includes the following steps: Weigh out the following ingredients by weight percentage: 0.1g of norcantharidin, 2.5g of phospholipid (egg yolk lecithin E80), 0.625g of membrane stabilizer (cholesterol), 12.5g of oil phase matrix (medium-chain triglycerides), 0.075g of co-emulsifier (oleic acid), 1.5g of emulsifier (soybean lecithin 80), 7g of gel matrix (carbomer 980), 3.125g of humectant (glycerin), and 972g of purified water. Add 872g of purified water to 7g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain blank gel; 2.5 g of phospholipid, 0.625 g of film stabilizer, and 10 g of anhydrous ethanol were mixed and heated to 40 °C under nitrogen atmosphere and stirred for 0.5 h until a clear solution was obtained. 0.1 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 40 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 40 °C, a complex was obtained. 12.5 g of oil phase matrix and 0.075 g of co-emulsifier were mixed with the complex and heated and stirred under nitrogen atmosphere at 40 °C for 0.5 h until a clear solution was obtained, yielding the oil phase. 1.5 g of emulsifier and 3.125 g of humectant were added to 100 g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 40 °C until a clear solution was obtained, yielding the aqueous phase. The aqueous phase was quickly added to the oil phase, and 10000... Shear at rpm for 1.5 min, pre-homogenize once at 0 bar using high pressure homogenizer, and then perform stepwise pressure-increasing homogenization at 100 bar, 300 bar, 500 bar and 800 bar. The stepwise pressure-increasing homogenization is to homogenize three times at each set pressure before increasing to the next pressure for homogenization. The temperature during homogenization is 20℃, to obtain the norcantharidin emulsion. The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.0 with triethanolamine to obtain the norcantharidin emulsion.

[0063] Comparative Example 3 High-pressure homogenization was not used in the emulsification step; instead, ordinary mechanical stirring was used for emulsification. The types and amounts of other raw materials and the preparation methods were the same as in Example 1.

[0064] A method for preparing a cantharidin latex includes the following steps: Weigh out the following ingredients by weight percentage: 0.25g of norcantharidin, 2.5g of phospholipid (egg yolk lecithin E80), 0.625g of membrane stabilizer (cholesterol), 12.5g of oil phase matrix (medium-chain triglycerides), 0.075g of co-emulsifier (oleic acid), 1.5g of emulsifier (soybean lecithin 80), 7g of gel matrix (carbomer 980), 3.125g of humectant (glycerin), and 972g of purified water. Add 872g of purified water to 7g of gel matrix, stir to disperse evenly, and allow to swell fully for 12h to obtain blank gel; 2.5 g of phospholipid, 0.625 g of film stabilizer, and 10 g of anhydrous ethanol were mixed and heated to 40 °C under nitrogen atmosphere and stirred for 0.5 h until a clear solution was obtained. 0.25 g of norcantharidin (pre-dissolved in 5 g of anhydrous ethanol) was added, and the mixture was stirred at 100 r / min under nitrogen atmosphere at 40 °C for 4 h. After removing the anhydrous ethanol by rotary evaporation under heating at 40 °C, a complex was obtained. 12.5 g of oil phase matrix and 0.075 g of co-emulsifier were mixed with the complex and heated and stirred under nitrogen atmosphere at 40 °C for 0.5 h until a clear solution was obtained, yielding the oil phase. 1.5 g of emulsifier and 3.125 g of humectant were added to 100 g of purified water, and the mixture was sheared at 4000 rpm for 1 min under nitrogen atmosphere at 40 °C until a clear solution was obtained, yielding the aqueous phase. The aqueous phase was rapidly added to the oil phase, and 10000... Shear at rpm for 1.5 min, stir to emulsify, and obtain norcantharidin emulsion; The norcantharidin emulsion and the blank gel were stirred and mixed at 25°C, and the pH was adjusted to 7.0 with triethanolamine to obtain the norcantharidin emulsion.

[0065] Application Example 1 I. The physicochemical properties of the norcantharidin latex prepared under the formulation conditions of Examples 1-11 and Comparative Examples 1-3 were evaluated, and the results are shown in Tables 1-3 below: Table 1. Physicochemical properties of the cantharidin latex from Examples 1-6

[0066] Table 2 Physicochemical properties of norcantharidin latex from Examples 7 to 11

[0067] Table 3 Physicochemical properties of cantharidin latex from Comparative Examples 1-3

[0068] To compare and evaluate the skin retention performance of the formulation of this invention, a norepinephrine aqueous solution prepared at the same concentration (0.25 mg / g) as the latex in Example 1 above was used as a control formulation, and its skin drug retention was measured under the same test conditions. The results showed that the drug retention per unit area of ​​the norepinephrine aqueous solution at the same concentration was 18.37 μg / cm². 2 This indicates that the latex formulation of the present invention can increase the retention and efficacy of norcantharidin.

[0069] In Comparative Example 1, the absence of phospholipids prevented norcantharidin from forming a stable complex structure with the phospholipids. This resulted in a lack of an effective interfacial stabilizing layer at the oil-water interface during emulsification, leading to easy aggregation and coarsening of droplets after high-pressure homogenization. Consequently, the latex particles exhibited uneven particle size distribution and increased particle size. In Comparative Example 2, when the amount of norcantharidin was below the range defined in this invention, the interfacial structure formed between the active ingredient, phospholipids, and film stabilizer was insufficient, affecting the stable encapsulation of droplets and the density of the interface. In Comparative Example 3, no high-pressure homogenization emulsification process was used; emulsification was performed only through ordinary mechanical stirring. This resulted in insufficient shear energy provided during emulsification, leading to larger droplet sizes in the primary emulsion and insufficient interfacial film formation, resulting in a significant increase in particle size.

[0070] In this invention, the high-pressure homogenization emulsification process and the phospholipid component have a synergistic effect in controlling the particle size of the latex and the stability of the system. On the one hand, the high-pressure homogenization process can further refine the oil droplets in the primary emulsion under the combined action of high shear force, cavitation force and impact force, so that the droplet size is significantly reduced and tends to be uniform. On the other hand, phospholipid molecules can be rapidly adsorbed and oriented at the newly formed oil-water interface during the high-pressure homogenization process, forming an interfacial film with a certain degree of flexibility and strength, thereby effectively inhibiting the aggregation and coarsening of droplets during subsequent processing and storage.

[0071] When high-pressure homogenization is not used or phospholipid components are lacking, insufficient energy is provided during emulsification or a stable interfacial structure is difficult to form, resulting in limited droplet refinement, a wider particle size distribution, and a significant increase in particle size. Consequently, the stability and skin retention properties of the latex system decrease. Therefore, the synergistic effect of high-pressure homogenization and phospholipid components is a key technical factor in obtaining a norepinephrine latex with smaller, more uniform, and stable particle size.

[0072] As can be seen from the physicochemical properties of Examples 1-11, the norcantharidin latex prepared within the formulation and process conditions defined in this invention exhibits excellent physicochemical properties. Specifically, after constructing a composite interface structure using phospholipids and a membrane stabilizer, and combining it with multi-stage high-pressure homogenization, the resulting emulsion particle size is significantly refined, with a concentrated and uniform particle size distribution. After mixing with the gel matrix to form the latex, the droplets can be uniformly dispersed in the gel network structure. Compared with the comparative sample, the latex in the examples of this invention has significant advantages in particle size control and dispersion uniformity, indicating that there is a synergistic effect between the active ingredient dosage range, the phospholipid to membrane stabilizer ratio, and the multi-stage high-pressure homogenization process parameters defined in this invention, which can effectively improve the structural stability and quality consistency of the latex system.

[0073] Therefore, the cantharidin latex protected by this invention not only has good uniformity, but also facilitates the stable distribution of active ingredients and the exertion of subsequent application effects, demonstrating significant technical advantages.

[0074] II. Skin irritation tests were conducted on the cantharidin latex and cantharidin cream (cantharidin cream was purchased from Hainan Bikai Pharmaceutical Co., Ltd., trade name: Youslow) prepared under the formulation conditions of Examples 1-6, Comparative Examples 1 and 3 of the present invention. The specific implementation plan is as follows: Skin irritation: The experimental animals were healthy adult female SD rats. Before the experiment, the skin on the back of the rats was shaved and the application area (1.5cm × 1.5cm) was marked. Three application areas were marked on the back of each rat. The three application areas were, in order, the blank latex group (the blank latex was prepared in the same way as in Example 1 except that no cantharidin was added), the nocantharidin latex group of the present invention, and the untreated group. The application was performed 6 hours apart, 3 times. The erythema and edema on the back of the rats were visually observed and scored at 0h, 1h, 6h, 12h, 24h, 30h, 36h, and 48h after administration (no erythema). 0 points for mild erythema, 1 point for moderate erythema, 2 points for severe erythema, 3 points for purplish-red spots to mild eschar formation, 4 points for no edema, 0 points for mild edema, 1 point for moderate edema, 2 points for severe edema (skin raised 1mm with clear outline), 3 points for severe edema (skin raised more than 1mm and enlarging), and 4 points for irritation. The scores indicate the presence and intensity of irritation: 0.00-0.49 for no irritation, 0.50-2.99 for mild irritation, 3.00-5.99 for moderate irritation, and 6.00-8.00 for strong irritation. The experimental results of the formulation of this invention are shown in Table 4. Table 4 Results of Skin Irritation Tests

[0075] The above results indicate that: Examples 1, 3, and 6 all had an stimulation score of 0 points from 1 to 48 hours; Example 2 had a stimulation score of 0.2 points from 1 to 48 hours; Example 4 had a stimulation score of 0.4 points from 1 to 48 hours; and Example 5 had a stimulation score of 0.3 points from 1 to 48 hours. This suggests that the norcantharidin latex of Examples 1-6 did not significantly irritate the intact skin of SD rats. Comparative Example 1 had a stimulation score of 3.4 points from 1 to 48 hours. Due to the absence of phospholipids, norcantharidin lacked the protection of its complex structure, increasing direct contact between the drug and the skin, leading to stronger irritation. Comparative Example 3 had a stimulation score of 1.7 points from 1 to 48 hours. The lack of high-pressure homogenization emulsification and the inability to effectively stabilize the emulsion droplets through stirring alone resulted in uneven drug release, leading to some irritation. The cantharidin cream had a stimulation score of 3.0 points from 1 to 48 hours, indicating moderate irritation. Prolonged skin irritation is strong and may easily cause allergies or discomfort. In summary, the cantharidin emulsion prepared by this invention has no significant skin irritation, thus enhancing the safety of the formulation.

[0076] III. First, regarding the efficacy evaluation of the norcantharidin latex prepared in Example 1 of this invention in a condyloma acuminata model, the specific implementation plan is as follows: Healthy male rabbits were used as the animals. Condyloma acuminata model construction: One week prior to the experiment, hair was removed from symmetrical areas (approximately 4cm × 4cm) on both sides of the rabbit's spine. Rabbit-derived papillomavirus suspension was inoculated into the shaved skin. The growth of verrucous growth was observed daily for two weeks. The model was considered successfully constructed when typical condyloma acuminata-like lesions (verrucous protrusions with a rough surface) appeared on the skin. The diameter of the verrucous lesions was ≥2mm, and their volume steadily increased over three consecutive days.

[0077] After the model was constructed, the rabbits were randomly divided into four groups: the model control group (rabbits with successful modeling, with blank latex applied to the warts), the positive control group (rabbits with successful modeling, with cantharidin cream 2.5 mg / cm² applied to the warts), and the positive control group (rabbits with successful modeling, with cantharidin cream 2.5 mg / cm² applied to the warts). 2 (2.5 mg / cm³ of norcantharidin latex) 2 (For rabbits with successfully modeled warts, a low dose of norcantharidin emulsion was applied to the warts.) The high-dose norcantharidin emulsion group (5 mg / cm²) was also included. 2 (For rabbits with successfully established models, a high dose of norcantharidin emulsion was applied to the warts). The drug was administered to an equal area of ​​the dorsal skin lesions in each group of animals for a period of 2 weeks. Changes in the skin lesions were observed daily during this period, and relevant indicators were measured after the drug administration was completed.

[0078] 24 hours before the start of administration, the skin lesions on the back of the rabbits were cleaned with physiological saline. Then, the norepinephrine emulsion was evenly applied to the skin lesions. The changes in the volume of the warts on the back of the rabbits and the regression rate were observed on the 3rd, 7th, 10th and 14th days after administration.

[0079] The anti-wart effect of the norepinephrine latex of this invention on a condyloma acuminata model is expressed as wart regression rate (WRR%): .

[0080] In this embodiment, the dosage of norcantharidin emulsion is 2.5 mg / cm³. 2 5mg / cm 2 As the experimental group, cantharidin cream (5 mg / cm³) commonly used in clinical practice was used. 2 As a control, the anti-wart effect in the condyloma acuminata model of the embodiment was examined. The results of the anti-wart effect of the present invention are shown in Table 5.

[0081] Table 5. Anti-wart effect in the condyloma acuminata model of Example 1.

[0082] Table 5 shows that by comparing the anti-wart effects of different doses of topical cantharidin emulsion, the topical cantharidin emulsion of this invention has a strong anti-wart effect, and the high-dose group is even more effective, indicating that the cantharidin emulsion of this invention has a certain anti-condyloma acuminata effect. Compared with the positive control cantharidin cream, the cantharidin emulsion of this invention, at the same dosage (2.5 mg / cm³), has a better anti-warts effect. 2 ), which has a stronger wart-inhibiting effect.

[0083] To verify the universality and effectiveness of the latex agent protected by this invention, Examples 2, 6, and 10, which fall within the lower limit, median, and upper limit of the parameter range, were selected and subjected to pharmacodynamic evaluation using the same experimental methods as the norcantharidin latex agent prepared in Example 1 and the clinically commonly used cantharidin cream. The pharmacodynamic tests were conducted using a condyloma acuminata model to investigate the effects of different latex agents on wart clearance (14 days) and recurrence trends. The specific experimental methods were consistent with those described in Example 1. Qualitative pharmacodynamic evaluations were performed on Example 1, representative Examples 2, 6, and 10, and the cantharidin cream; the results are shown in Table 6. Comparative Examples 1, 2, and 3 were also subjected to pharmacodynamic evaluations using the same experimental methods as the norcantharidin latex agent prepared in Example 1; qualitative pharmacodynamic evaluations were performed on Comparative Examples 1 to 3; the results are shown in Table 7.

[0084] Table 6. Qualitative pharmacodynamic evaluation results of representative examples.

[0085] Pharmacodynamic evaluation results showed that the cantharidin latex preparations prepared in Examples 2, 6, and 10 were basically consistent with Example 1 in terms of wart clearance effect, onset of action, and recurrence trend. All preparations exhibited significant wart clearance effects, rapid onset of action, and low recurrence trend, indicating that within the formulation composition and preparation conditions defined in the claims of this invention, different implementation methods can achieve stable and good pharmacodynamic effects. Compared with cantharidin cream, the latex preparation of this invention showed a higher wart clearance rate, faster onset of action, and lower recurrence rate under the same experimental conditions, demonstrating superior therapeutic stability and persistence. This indicates that the specific latex structure of this invention can effectively improve the local utilization efficiency of the active ingredient.

[0086] Table 7. Qualitative pharmacodynamic evaluation results of the comparative examples.

[0087] Compared with the embodiments of the present invention, the preparations prepared by Comparative Examples 1 to 3 showed significantly reduced wart removal effect and efficacy, and increased recurrence rate, with overall efficacy significantly inferior to the embodiments of the present invention.

[0088] IV. Stability tests were conducted on the norcantharidin latex prepared under the formulation conditions of Examples 1 to 6 of the present invention. The specific implementation scheme is as follows: Centrifugation stability: Take 10g of the cantharidin emulsion of the present invention, put it into a clean sealed centrifuge tube with graduations, and centrifuge at 3000rpm for 30min, 6000rpm for 15min, and 10000rpm for 15min respectively, and observe whether there are changes such as layering, turbidity, and color.

[0089] High-temperature stability: Take 20g of the cantharidin emulsion of this invention, put it into a clean, sealed vial, and place it in a 60℃ oven for 10 days. Take samples every 24 hours to observe whether layering, turbidity, or color changes occur. Take samples on the 5th, 10th, and 15th days to observe whether layering, turbidity, or color changes occur, and determine the drug content using HPLC to check for any changes.

[0090] Low temperature stability: Take 20g of the cantharidin emulsion of the present invention, put it into a sealed clean vial, place it in a refrigerator at 4℃ for 1 month, and observe whether there are changes such as layering, turbidity, or color.

[0091] Freeze-thaw cycle test: Take 20g of the cantharidin latex of this invention and put it into a sealed clean vial. The latex is subjected to a freeze-thaw cycle for 3 days and 72 hours. 60℃, 16h to 4℃, 8h is one cycle. From heating to cooling, and then from low temperature to high temperature, 3 cycles are carried out. Changes such as layering, turbidity, and color are observed.

[0092] Stability at room temperature: Take 20g each of the cantharidin emulsion from Examples 1-6 of this invention and the clinically commonly used cantharidin cream, and put them into sealed clean vials. Place them at room temperature for 24 months and observe whether there are any changes such as layering, turbidity, or color.

[0093] The stability test results of the cantharidin latex prepared in Examples 1 to 6 of this invention are shown in Tables 8, 9 and 10.

[0094] Table 8. Stability test results of norcantharidin in Examples 1 to 6 of the present invention.

[0095] Table 9. Drug content results of norcantharidin after high-temperature experiment in Examples 1-6 of the present invention.

[0096] Table 10 Comparison of room temperature stability of the cantharidin emulsion and cantharidin cream in Examples 1-6 of the present invention.

[0097] Experimental results show that the norcantharidin emulsion of this invention did not undergo stratification, phase change, or color change under low temperature, high temperature, or high-speed centrifugation, indicating that the norcantharidin emulsion of this invention is relatively stable. In the high-temperature experiment among the influencing factors, the drug content remained within the pharmacopoeia-defined range, indicating that the norcantharidin emulsion of this invention is stable. The norcantharidin emulsion exhibits significantly better stability at room temperature than cantharidin cream, maintaining good appearance and texture stability during prolonged storage.

[0098] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A cantharidin latex, characterized in that, The raw materials used to prepare the norcantharidin latex include the following components in parts by weight: 0.2-0.3 parts of norcantharidin, 2.0-3.0 parts of phospholipids, 0.5-0.75 parts of film stabilizer, 10-15 parts of oil phase matrix, 0.05-0.1 parts of co-emulsifier, 1.2-1.8 parts of emulsifier, 6.5-7.5 parts of gel matrix, 3.0-3.25 parts of humectant, and 950-1000 parts of water.

2. The norcantharidin latex according to claim 1, characterized in that, The phospholipid is any one or more of egg yolk lecithin, soybean phospholipid, hydrogenated soybean phospholipid, and synthetic phospholipid; the synthetic phospholipid is dipalmitoylphosphatidylcholine or distearate phosphatidylcholine; the membrane stabilizer is cholesterol, cetyl alcohol, transoleyl alcohol, stigmasterol, or β-sitosterol; the phospholipid, membrane stabilizer, and norcantharidin form a complex.

3. The norcantharidin latex according to claim 1, characterized in that, The gel matrix is ​​any one or more of the following: carbomer 940, carbomer 980, hydroxypropyl methylcellulose, methylcellulose, carboxymethylcellulose, carboxyethylcellulose, hydroxypropylcellulose, polyvinyl chloride, xanthan gum, guar gum, gum arabic, sodium alginate, chitosan, hyaluronic acid, polyethylene glycol monostearate, and poloxamer 407.

4. The norcantharidin latex according to claim 1, characterized in that, The oil phase matrix is ​​a medium-chain triglyceride, ethyl oleate, liquid paraffin, silicone oil, or cocoyl decanoate.

5. The norcantharidin latex according to claim 1, characterized in that, The emulsifier is any one or more of phosphatidylcholine, poloxamer, Tween 20, Tween 60, Span 20, Span 40, Span 80, propylene glycol monolaurate, and cetyl polyoxyethylene ether-20.

6. The norcantharidin latex according to claim 1, characterized in that, The moisturizer is glycerin, propylene glycol, polyethylene glycol, or sorbitol.

7. The norcantharidin latex according to claim 1, characterized in that, The co-emulsifier is oleic acid, linoleic acid, linolenic acid, stearic acid, hydroxypropyl methylcellulose stearoxy ether, sodium deoxycholate, or sodium diethyl succinate sulfonate.

8. The norcantharidin latex according to claim 1, characterized in that, The pH value of the norcantharidin latex is 7.0~7.

2.

9. A method for preparing the norcantharidin latex according to claims 1-8, comprising the following steps: The gel matrix and water were mixed for the first time to obtain a blank gel; The phospholipids, membrane stabilizer, and norcantharidin were mixed a second time to obtain a complex; The oil phase matrix, the co-emulsifier, and the complex are mixed in a third step to obtain the oil phase. The emulsifier, humectant, and water are mixed in a fourth step to obtain the aqueous phase. The aqueous phase was added to the oil phase and emulsified under high pressure homogenization to obtain a norepinephrine emulsion. The norcantharidin emulsion and the blank gel are mixed for the fifth time to obtain norcantharidin emulsion.

10. The use of the norcantharidin latex according to any one of claims 1 to 8 or the norcantharidin latex prepared by the preparation method according to claim 9 in the preparation of a medicament for treating viral skin warts; wherein the viral skin warts include common warts, flat warts, plantar warts or condyloma acuminata.

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