A liposome external medicine for treating diseases caused by viral infection of epithelial tissue

Abstract

The present application relates to a liposome external medicine for treating diseases caused by viral infection of epithelial tissue. The present application provides a liposome gel medicine for treating diseases caused by viral infection of epithelial tissue, and the active ingredient of the medicine is chloroquine phosphate. The present application provides a preparation method for preparing a medicine for treating diseases caused by viral infection of epithelial tissue. The chloroquine phosphate is prepared into a liposome gel, a paste, a spray, a lotion, a gargle, a suppository and other skin and mucous membrane used medicine preparations. The present application is used for treating diseases caused by viral infection of epithelial tissue, including herpes simplex virus and human papilloma virus.

Description

Technical Field

[0001] This invention relates to a medicament for treating diseases caused by viral infections of epithelial tissues, containing chloroquine phosphate as its active pharmaceutical ingredient. Specifically, chloroquine phosphate is prepared into gels, ointments, sprays, lotions, mouthwashes, suppositories, and other pharmaceutical preparations for use on the skin and mucous membranes. It is used to treat diseases caused by viral infections of epithelial tissues, including herpes simplex virus and human papillomavirus. Background Technology

[0002] Viral infections of epithelial tissues mainly manifest as skin and mucous membrane vesicles and wart-like growths. Herpes simplex virus and human papillomavirus are the main pathogenic microorganisms that cause skin and mucous membrane vesicles and wart-like growths.

[0003] Herpes simplex virus (HSV): Herpes simplex virus (HSV) belongs to the herpesvirus family and contains linear dsDNA. There are two serotypes of HSV: HSV-1 and HSV-2. Like varicella-zoster virus, HSV can infect epithelial cells and remain latent in nerve cells.

[0004] HSV infection is very common in the population, with close contact and sexual contact being the main routes of transmission. The virus enters the body through mucous membranes and broken skin. HSV-1 infection mainly affects the upper body, such as recurrent clusters of blisters at the junction of the lip and nasal mucosa, and keratoconjunctivitis. HSV-2 infection mainly affects the lower body and genitals; both male and female reproductive tracts can be invaded by HSV-2, manifesting as painful blister lesions.

[0005] Prevention: There is currently no HSV vaccine.

[0006] Treatment: Currently available anti-HSV drugs include idoxuridine, interferon, vidarabine, and acyclovir, but none of them can eliminate the latent virus or prevent the recurrence of latent virus infection.

[0007] Human papillomavirus (HPV) is an epitheliotropic virus, a small, double-stranded, closed-circular DNA virus with approximately 8,000 base pairs. It has eight early open reading frames (E1-E8), two late reading frames, and one non-coding long control region. HPV primarily infects humans, growing mainly on the skin and mucous membranes near the reproductive organs. Depending on the site of infection, it is classified as cutaneous warts, condyloma acuminata, mucosal condyloma acuminata, and mucosal papillomas. HPV does not infect other human tissues or any animals. Modern research has demonstrated that HPV infection is associated with the development and progression of cervical cancer, head and neck cancer, and other cancers.

[0008] Prevention: In clinical practice, vaccines are used to prevent some related diseases caused by HPV infection. The vaccines used include bivalent vaccines (HPV16, 18), quadrivalent vaccines (bivalent + HPV11, 6), and nonavalent vaccines (quadrivalent + HPV31, 33, 45, 52, and 58). These vaccines can only prevent 9 of the more than 110 types of HPV in clinical practice, and the clinical cost is high and the coverage rate is low.

[0009] Treatment: 1. Physical therapy: Primarily includes CO2 laser and liquid nitrogen cryotherapy. This therapy acts on the epidermal layer of epithelial cells but cannot penetrate to the basal cells, thus failing to eliminate HPV within them and leading to a high recurrence rate after treatment. If it penetrates to the basal cells, the basal cells will be destroyed, preventing the formation of the stratum corneum and ultimately affecting the integrity of the epidermis, resulting in scarring. 2. Drug therapy: Podophyllotoxin, 5% imiquimod cream, recombinant human interferon α2b gel, 15% tea polyphenol cream, etc. Although there are many traditional Chinese medicine formulas available clinically, most are modifications of prescriptions written by doctors; no approved traditional Chinese medicine preparations for treating HPV infection-related diseases have yet been found on the market.

[0010] In summary, there is currently no cure for HSV, and this invention provides a new treatment option.

[0011] There are currently no safe, effective, or completely curative drugs or methods for HPV infection in clinical practice. Physical therapy, podophyllotoxin, and traditional Chinese medicine preparations all have drawbacks such as high risk, high incidence of adverse reactions, low efficacy, and easy recurrence.

[0012] While approved immunostimulants such as imiquimod, interferon, and tea polyphenols have good safety profiles when used alone, their efficacy is low and they cannot achieve a complete cure. Therefore, developing drugs that can completely eliminate HPV and cure related diseases caused by HPV infection is an urgent issue that needs to be addressed. This is urgently needed clinically and has significant social benefits.

[0013] Chloroquine is an antimalarial drug that has been on the market for over 60 years and has significant antiviral activity. In 1969, Ingot et al. in the UK first reported chloroquine's effectiveness against New Castle Disease Virus (NDV) and other viruses. In addition, chloroquine also shows significant in vitro inhibitory effects against varicella-zoster virus, HIV, zika virus, BK virus, Ebola, Japanese encephalitis virus, and influenza virus.

[0014] The antiviral mechanism of chloroquine is not fully understood. Some studies suggest that chloroquine may exert its antiviral effect by inhibiting the binding of the virus to the angiotensin 2 receptor (ACER2) on the cell membrane; or it may exert its antiviral effect by increasing the pH of the cell lysosome, thereby altering the external environment of the virus and preventing the assembly of viral proteins and nucleic acids.

[0015] The inventors have discovered that chloroquine is highly effective against HPV and HSV, and its therapeutic effect is even better when combined with immunostimulants. Chloroquine has a strong inhibitory effect on both HPV and HSV. When used in conjunction with immunostimulants, it can enhance the body's immune function and directly kill the virus, achieving a synergistic effect through a dual mechanism to treat viral infection-related diseases. Furthermore, we have creatively changed the traditional systemic administration of chloroquine (oral and intravenous) to topical administration through the skin and mucous membranes. This method of administration is best suited for viral infections that target phagetropic epithelial tissues, reaching the viral infection target site with minimal drug exposure, thus significantly improving efficacy and safety. Summary of the Invention

[0016] The chloroquine described in this invention includes chloroquine, chloroquine phosphate, or other pharmaceutically acceptable salts of chloroquine.

[0017] The purpose of this invention is to provide a medicament for treating diseases caused by viral infections of epithelial tissue, which contains chloroquine phosphate.

[0018] Another object of the present invention is to provide a method for preparing a drug for treating diseases caused by viral infections of epithelial tissue, wherein the method comprises mixing chloroquine phosphate and conventional pharmaceutical excipients to prepare a pharmaceutical formulation.

[0019] Another object of the present invention is to provide a use for preparing a medicament for treating diseases caused by viral infections of epithelial tissue.

[0020] Specifically, the present invention provides a medicament for treating diseases caused by viral infections of epithelial tissue, which contains chloroquine phosphate.

[0021] The pharmaceutical composition of the present invention contains 1-10% chloroquine phosphate, more preferably 2-8%, and most preferably 5%.

[0022] The pharmaceutical compositions of the present invention can be formulated into preparations for topical administration via the skin or mucous membranes.

[0023] The pharmaceutical compositions of the present invention may be gels, ointments, sprays, lotions, mouthwashes, suppositories, films, coatings, liniments, or ointments. More preferably, they are gels, ointments, sprays, lotions, mouthwashes, or suppositories.

[0024] The pharmaceutical composition of the present invention is mixed with conventional pharmaceutical excipients to prepare a pharmaceutical formulation.

[0025] Methods for preparing liposome gel: (1) Prepare a primary blank liposome suspension by thin-film dispersion or reverse-phase evaporation, and obtain a secondary blank liposome suspension by high-pressure homogenization, microfluidic jet or ultrasonic pulverization; (2) Weigh the prescribed amount of chloroquine phosphate and dissolve it in the liposome suspension, adjust the pH to 6.0-8.0 with alkali, add 2% hydroxypropyl cellulose-GF to make it swell in the liposome suspension, filter aseptically, bottle and seal to obtain the chloroquine phosphate liposome gel product. The alkali used to adjust the pH is selected from sodium hydroxide, disodium hydrogen phosphate or sodium carbonate; The thin-film dispersion method is to weigh the prescribed amount of phospholipids, cholesterol and vitamin E, dissolve them in 2-100 ml of ether, remove the organic solvent by vacuum distillation on a thin-film evaporator to form a uniform lipid film, and then add 1-20 ml A 0.01-0.30M pH 2.0-5.0 buffer solution is added, and the mixture is continuously rotated until the lipid membrane hydrates to form a milky white primary blank liposome suspension. This is then subjected to high-pressure homogenization, microfluidic jetting, or ultrasonic pulverization to obtain a secondary blank liposome suspension. The buffer solution used is selected from citrate, phosphate, or carbonate buffer systems. The reverse-phase evaporation method involves weighing the prescribed amounts of phospholipids, cholesterol, and vitamin E, dissolving them in ether, and preparing a 0.01-0.30M pH 2.0-5.0 buffer solution. 2-100 ml of the ether solution is mixed with 1-20 ml of the buffer solution to form an emulsion. The organic solvent is removed using a thin-film evaporator to obtain the primary blank liposome suspension. The buffer solution used is selected from citrate, phosphate, or carbonate buffer systems. The gel matrix is ​​then thoroughly mixed to form a semi-solid or viscous liquid with gel properties, thus preparing the liposome gel containing the drug.

[0026] Method for preparing the spray: Dissolve chloroquine phosphate with a suitable solvent and excipients, mix well, and fill into a bottle equipped with a spray device to prepare a spray containing the drug.

[0027] Method for preparing ointments: Mix chloroquine phosphate with a suitable matrix to form a semi-solid solution or suspension ointment, and package it in a suitable container to prepare an ointment containing the drug.

[0028] Method for preparing suppositories: Mix chloroquine phosphate and a suitable matrix evenly, inject into a mold, cool, and dispense to prepare suppositories containing the drug composition.

[0029] Method for preparing mouthwash: Dissolve chloroquine phosphate and suitable excipients, flavoring agents and solvents, mix evenly, and package to prepare a mouthwash containing the drug composition.

[0030] Method for preparing the lotion: Dissolve chloroquine and suitable excipients in a solvent, mix thoroughly, and dispense into a container to prepare a lotion containing the drug composition.

[0031] In the process of preparing the drug into a pharmaceutical formulation, a transdermal absorption enhancer may be added. The transdermal absorption enhancer is selected from azone, oleic acid, isopropyl myristate, borneol, menthol, essential oil, lactone, or a mixture thereof.

[0032] In the process of preparing the drug into a pharmaceutical formulation, surfactants and / or cosolvents may be added. The surfactants or cosolvents are selected from Tween-80, ethanol, sodium dodecyl sulfate, Span-80, etc., to increase the solubility of chloroquine and immune function enhancers.

[0033] In the process of preparing the pharmaceutical composition of the present invention into a pharmaceutical formulation, antibacterial agents and / or preservatives may be added. The antibacterial agents and preservatives may be selected from benzalkonium bromide, benzalkonium chloride, benzyl alcohol, benzoic acid, phenol, lactic acid, boric acid, chlorobutanol, sorbic acid, propylene glycol, sodium benzoate, thimerosal, acetic acid, methylparaben, ethylparaben, propylparaben, butylparaben, sodium propylparaben, sodium methylparaben, etc.

[0034] The pharmaceutically active ingredients of the present invention include various pharmaceutical forms thereof, specifically: The active pharmaceutical ingredient of this invention, chloroquine, includes chloroquine, which may be a pharmaceutical salt or similar derivative.

[0035] We conducted various pharmacodynamic and toxicological studies using drugs containing chloroquine phosphate and their preparations for skin and mucous membrane applications.

[0036] Through our screening of a series of promising drugs, we were very surprised to find that chloroquine phosphate liposomal drugs have the potential pharmacodynamic properties to clinically cure diseases caused by viral infections of epithelial tissues.

[0037] We have found that this drug can treat diseases caused by viral infections of epithelial tissue, including HSV infection and HPV infection.

[0038] We were surprised to find that the drug containing chloroquine phosphate of the present invention has significant beneficial effects, specifically manifested in: This invention has surprisingly discovered that chloroquine phosphate, an old drug with over 60 years of history in treating malaria, possesses pharmacodynamic properties related to diseases caused by viral infections of epithelial tissues. Studies have shown that chloroquine has a strong inhibitory effect on both HSV and HPV, and exhibits a clear dose-response relationship.

[0039] In addition, this invention has surprisingly discovered that, in order to improve clinical efficacy, we prepared chloroquine phosphate into a topical drug formulation using advanced liposome formulation technology. In vitro multi-cell line antiviral experiments showed that the chloroquine phosphate liposome gel drug had a significant virus-killing effect, which was more than 20 times that of the antiviral drug cidofovir.

[0040] Furthermore, we creatively changed the traditional systemic administration of chloroquine phosphate (oral and intravenous) to topical administration via the skin and mucous membranes. This method of administration is best suited for viral infections that target these types of phobetic epithelial tissues, achieving the target site of viral infection with minimal drug exposure.

[0041] The chloroquine phosphate-containing drug of the present invention can directly inhibit and kill viruses, as well as enhance the body's immunity and resist viral infection. Therefore, the drug of the present invention can effectively eliminate viruses and can be used to prevent and treat diseases caused by viral infection of epithelial tissue.

[0042] Existing oral tablets and injections of chloroquine result in high in vivo exposure, with relatively low drug concentrations reaching epithelial tissues. This leads to poor local viral inhibition and significant side effects. Currently approved immunostimulants such as imiquimod, interferon, and tea polyphenols, while showing good safety profiles when used alone, have low efficacy and cannot achieve a complete cure. Our invented drug composition, administered topically through the skin and mucous membranes, reaches the viral infection target site with minimal in vivo exposure. This route of administration is ideally suited for viral infections that phagocytose epithelial tissues, producing a synergistic effect of directly inhibiting and killing the virus while enhancing the body's immunity and resistance to viral infection.

[0043] Although HPV only infects humans and not other animals, which limits the feasibility of conducting efficacy experiments on animal HPV infection models, we have demonstrated the synergistic effect of this invention against HPV through in vitro cell culture antiviral experiments.

[0044] Our research has demonstrated that the drug of this invention can completely eliminate viruses in epithelial tissue cells with low adverse reactions, thus overcoming the shortcomings of existing therapeutic drugs and methods, such as high clinical application risk, high adverse reactions, low efficacy, and easy recurrence.

[0045] If the drug of this invention is applied clinically, it can enhance the body's immune function and directly kill viruses, thereby treating viral infection-related diseases and significantly improving its efficacy and safety.

[0046] It can be predicted that the drug of this invention will bring new hope to the treatment of diseases caused by viral infections of epithelial tissues. Example

[0047] Detailed Implementation: The present invention is further illustrated below with examples. It should be understood that these examples are merely for illustrating the present invention and are not intended to limit the present invention.

[0048] Example 1: Weigh 500 mg of soybean lecithin, 100 mg of cholesterol, and 20 mg of vitamin E, dissolve them in 20 ml of ether, mix thoroughly, and place the solution in a ground-glass stoppered round-bottom flask. Evaporate the organic solvent under reduced pressure using a rotary evaporator in a constant temperature water bath at 37-40°C, allowing the lecithin and other film-forming materials to form a uniform lipid film at the bottom of the flask. Add 10 ml of 0.1 M citrate-sodium citrate buffer solution (pH 3.6) to the lipid film, and rotate the evaporator until the lipid film hydrates and becomes a milky white liposome suspension. Ultrasonically pulverize to reduce particle size. Weigh 10 mg of chloroquine phosphate, dissolve it in the liposome suspension, adjust the pH to 7.0 with disodium hydrogen phosphate, and let it stand at room temperature for 20 minutes. The encapsulation efficiency was measured to be 93%, and the average particle size was 110 nm. Dissolve 1000 mg of trehalose in the liposome suspension, aseptically filter (membrane filter pore size 220 nm), dispense into vials, and freeze-dry. The freeze-dried liposomes were hydrated and recombined with water for injection, and the encapsulation efficiency was measured to be 98%, with an average particle size of 128 nm.

[0049] Example 2: 420 mg of dipalmitoylphosphatidylcholine (DPPC), 60 mg of phosphatidylethanolamine (PE), 100 mg of cholesterol, and 20 mg of vitamin E were weighed and dissolved in 10 ml of diethyl ether. The mixture was thoroughly mixed and placed in a round-bottom flask with a ground glass stopper. The organic solvent was evaporated under reduced pressure using a rotary evaporator in a constant temperature water bath at 37-40°C, allowing the phospholipids and other film-forming materials to form a uniform lipid film at the bottom of the flask. 5 ml of 0.1 M citrate-sodium citrate buffer solution (pH 3.6) was added to the lipid film, and the mixture was rotated in the rotary evaporator until the lipid film hydrated and became a milky white liposome suspension. The suspension was then ultrasonically pulverized to reduce the particle size. 10 mg of chloroquine phosphate was weighed and dissolved in the liposome suspension. The pH was adjusted to 7.0 with disodium hydrogen phosphate, and the suspension was left at room temperature for 20 minutes. The encapsulation efficiency was measured to be 94%, and the average particle size was 200 nm. 1000 mg of trehalose was dissolved in the liposome suspension, aseptically filtered (membrane filter pore size 220 nm), dispensed into vials, and lyophilized. The lyophilized liposomes were rehydrated and recombined with water for injection, and the encapsulation efficiency was measured to be 95%, with an average particle size of 560 nm.

[0050] Example 3: 1000 mg of lecithin, 100 mg of cholesterol, and 20 mg of vitamin E were weighed and dissolved in 100 ml of ether. The mixture was stirred until homogeneous, and then 20 ml of 0.1 M citrate-sodium citrate buffer solution (pH 3.6) was added to form an emulsion. This emulsion was placed in a ground-glass round-bottom flask and the organic solvent was evaporated under reduced pressure using a rotary evaporator in a constant temperature water bath at 37-40°C until a milky white liposome suspension was obtained. The suspension was then homogenized under high pressure to reduce the particle size. 10 mg of chloroquine phosphate was weighed and dissolved in the liposome suspension. The pH was adjusted to 7.4 with disodium hydrogen phosphate, and the suspension was left to stand at room temperature for 20 minutes. The encapsulation efficiency was measured to be 90%, and the average particle size was 120 nm. 500 mg of sucrose and 500 mg of lactose were dissolved in the liposome suspension, aseptically filtered (membrane filter pore size 220 nm), dispensed into vials, and freeze-dried. The freeze-dried liposomes were hydrated and recombined with water for injection, and the encapsulation efficiency was measured to be 92%, with an average particle size of 600 nm.

[0051] Example 4: 470 mg of soybean lecithin, 100 mg of distearate phosphatidylethanolamine-polyethylene glycol (DSPE-PEG2000), 20 mg of cholesterol, and 20 mg of vitamin E were weighed and dissolved in 40 ml of diethyl ether. The mixture was thoroughly mixed, and then 10 ml of 0.1 M citrate-sodium citrate buffer solution (pH 3.6) was added to form an emulsion. This emulsion was placed in a ground-glass stoppered round-bottom flask and the organic solvent was evaporated under reduced pressure using a rotary evaporator at a constant temperature of 37-40°C until a milky white liposome suspension was obtained. The suspension was then homogenized under high pressure to reduce particle size. 10 mg of chloroquine was weighed and dissolved in the liposome suspension. The pH was adjusted to 7.0 with disodium hydrogen phosphate, and the suspension was allowed to stand at room temperature for 20 minutes. The encapsulation efficiency was measured to be 98%, and the average particle size was 87 nm. 1000 mg of trehalose was dissolved in the liposome suspension, aseptically filtered (membrane filter pore size 220 nm), dispensed into vials, and freeze-dried. The freeze-dried liposomes were hydrated and recombined with water for injection, and the encapsulation efficiency was measured to be 86%, with an average particle size of 467 nm.

[0052] Example 5: Stability test of the pharmaceutical composition formulation of the present invention Using the formulation samples from Examples 1 to 4 above, and simulating commercially available packaging, accelerated stability (storage conditions: 40±2℃ / 75%±5%RH) and long-term stability (storage conditions: 25±2℃ / 60%±5%RH) experiments were conducted.

[0053] Experimental results: Chloroquine has stable drug properties and no compatibility issues with the selected immune function enhancer. The combination of the two will not produce any related effects that would lead to degradation or other quality changes. The drug composition has good compatibility with other excipients in the formulation and will not affect the shape of the drug composition or the physical and chemical properties of the formulation.

[0054] Example 6: Assay of HPV11.HaCaT cell proliferation activity (MTT assay) The effect of chloroquine phosphate liposome gel on the activity of HPV11.HaCaT cells (HPV11.HaCaT) was analyzed using the MTT assay, with cidofovir used as a positive control in this study.

[0055] An appropriate amount of chloroquine phosphate (purity >99.0%) was diluted with DMEM cell culture medium containing 10% fetal bovine serum. Seven different concentrations of each drug were prepared, with concentration ranges shown in Table 1. HPV11.HaCaT cells were seeded into 96-well plates at a density of 6 × 10⁴ cells per well, with three replicates for each concentration of each drug. Cells were cultured at 37°C in a 5% CO₂ incubator. When the cells were in the exponential proliferation phase, different concentrations of the seven drugs were added to the diluted cell culture medium. After culturing for another 24 hours at 37°C in a 5% CO₂ incubator, the culture medium was aspirated. HPV11.HaCaT cell viability was determined using the MTT assay. The results showed that the survival rate of HPV11.HaCaT cells was greater than 90% for all seven drugs within the experimental concentration range. Preliminary experiments were conducted based on the concentration range that resulted in 90% cell survival to determine the concentration range for the IC50 assay (Table 1).

[0056] Table 1. Effects of seven drugs on HPV11.HaCaT cell activity and IC50 concentration range. chloroquine 0.05-15 μg / ml 0.05-15 μg / ml 0.125-8 μg / ml 0.125-8 μg / ml Example 7: Effect on HPV11 DNA copy number in HPV11.HaCaT cells (IC50) HPV11.HaCaT cells were used, with 18-22 copies of HPV11 DNA per cell, to detect the inhibitory effect of chloroquine phosphate on HPV11.HaCaT cell HPV11 DNA replication.

[0057] HPV11.HaCaT cells were seeded at a density of 5 × 10⁴ cells per well in 96-well plates and cultured at 37°C in a 5% CO₂ incubator for 24 hours, after which the culture medium was removed. The seven drugs were diluted to different concentrations using DMEM cell culture medium containing 10% fetal bovine serum, according to the concentration ranges determined in the preliminary experiments in Table 1. The diluted drug-containing cell culture media were added to the wells after removing the culture medium and cultured at 37°C in a 5% CO₂ incubator for another 24 hours. A blank group without HPV11 normal HaCaT cells and a control group with an equal volume of culture medium were also included, with three replicates in each group. HPV11 DNA copy number was detected by FQPCR. The results showed that the concentration (IC50) at which the above drugs inhibited HPV11 DNA copy number by 50% was chloroquine phosphate at 1.0 µg / ml.

Claims

1. A medicine for treating diseases caused by viral infections of epithelial tissue, comprising chloroquine phosphate, wherein the chloroquine includes chloroquine phosphate and its pharmaceutically acceptable salts.

2. The drug according to claim 1, characterized in that, The content of chloroquine phosphate is 1-10%, more preferably 2-8%, and most preferably 5%.

3. The drug according to claim 2, characterized in that, The drug dosage forms mentioned are gels, ointments, sprays, lotions, mouthwashes, and suppositories.

4. The drug according to claim 3, characterized in that, The preparation process described is liposome technology.

5. The drug liposome according to claim 4, characterized in that, The liposomes contain phospholipids, cholesterol, and vitamin E.

6. The drug liposome according to claim 5, characterized in that, The liposome gel is obtained through the following steps: (1) a primary blank liposome suspension is prepared by thin-film dispersion or reverse-phase evaporation, and a secondary blank liposome suspension is obtained by high-pressure homogenization, microfluidization or ultrasonic pulverization; (2) the prescribed amount of chloroquine phosphate is weighed and dissolved in the liposome suspension, the pH is adjusted to 6.0-8.0 with alkali, 2% hydroxypropyl cellulose-GF is added to make it swell in the liposome suspension, sterilely filtered, bottled and capped to obtain the chloroquine phosphate liposome gel product. The alkali used to adjust the pH is selected from sodium hydroxide, disodium hydrogen phosphate or sodium carbonate; the thin-film dispersion method is to weigh the prescribed amount of phospholipids, cholesterol and vitamin E, dissolve them in 2-100 ml of ether, remove the organic solvent by vacuum distillation on a thin-film evaporator to form a uniform lipid film, and then add 1-20 ml of ether. A 0.01-0.30M pH 2.0-5.0 buffer solution is added, and the mixture is continuously rotated until the lipid membrane is hydrated into a milky white primary blank liposome suspension. This is then homogenized under high pressure, microfluidically, or ultrasonically to obtain a secondary blank liposome suspension. The buffer solution used is selected from a citrate buffer system, a phosphate buffer system, or a carbonate buffer system. The reverse-phase evaporation method involves weighing the prescribed amount of phospholipids, cholesterol, and vitamin E, dissolving them in ether, and preparing a 0.01-0.30M pH 2.0-5.0 buffer solution. 2-100 ml of the ether solution is mixed with 1-20 ml of the buffer solution to form an emulsion. The organic solvent is removed using a thin-film evaporator to obtain a primary blank liposome suspension. The buffer solution used is selected from a citrate buffer system, a phosphate buffer system, or a carbonate buffer system.

7. The drug according to claims 1 to 5, characterized in that, The drug is formulated for topical administration via the skin or mucous membranes.

8. The drug according to claim 6, characterized in that, The medications mentioned are gels, ointments, sprays, lotions, mouthwashes, suppositories, films, liniments, and ointments.

9. Use of the pharmaceutical composition according to claims 1 to 7 in the preparation of a medicament for treating diseases caused by viral infections of epithelial tissue.

10. The use of claim 7 in preparing a medicament for treating diseases caused by viral infections of epithelial tissue, wherein the virus is herpes simplex virus or human papillomavirus.