TW306878B - A topical pharmaceutical composition comprising aphidicolin for use in the treatment of cutaneous viral infection - Google Patents

Abstract

The present invention provides a pharmaceutical formulation containing aphidicolin or a derivative thereof for the topical treatment of cutaneous viral infection. The formulation comprises aphidicolin or a derivative thereof and a pharmaceutically acceptable topical vehicle. The invention also provides a method of treating cutaneous viral infection that comprises applying the formulation to a cutaneous site of viral infection. In one embodiment, the formulation is used to treat papillomavirus infection.

Description

Printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs ^ 06878 V. Description of the invention () The present invention is a W-medicine formulation containing phendicoline (aphidi C ο 1 i η > or its derivatives, used For local treatment of skin infections, such as: infections caused by papillary plaque virus and herpes virus. Many types of skin infections caused by skin lesions can be treated locally. Viruses that cause skin damage include, for example, papillary palsy Viruses and herpes viruses. These two viruses are both DNA viruses and require DNA polymerases for replication during infection. In this article, the M papilloma virus is used as an example to discuss in detail this type of skin infection, a virus that depends on DNA polysaccharides. Papilloma virus is a non-enveloped, icosahedral DNA virus that infects squamous epidermal cells. The virus particle contains a 8000_S-based double-stranded DMA molecule contained in a globular protein coat. Papilloma virus The anatomical structure of the genome is preserved at an extreme rate. Papilloma virus has strict breed specificity and produces squamous epidermal paralysis and hungry epidermal swollen sleep in its host. Identified more than 70 types of human papillary disease * (hereinafter referred to as "HPVs") cHPV-Ι can cause palm warts, while HPV-6 and HPV-11 cause laryngeal papillary epilepsy and warts (genital warts) , This is the fourth major disease transmitted by the hydrocarbon-based system. HPV-16, HPV-18, HPV-31, and HPV-33 can cause genital warts, and they are formed with genital intraepithelial neoplasia. These neoplasms may gradually Development of various cancers, including cervical cancer, kills about 500,000 people each year. The standard course of anti-disease therapy is the inhibition of viral polymerase to inhibit the replication of disease. This method has been used to develop many suitable for the treatment of herpes virus Infection. For example: Vidarabine (vidarabine) is phosphorylated in the cell to form a triphosphate derivative, which is more suitable for inhibiting the DNA polymerization of herpes disease than the human paper standard (CNS > Α4 specification (210X297mm) (Please read the notes on the back to write this page)

, 1T 4 Printed by the employee consumer cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 306878 V. Description of invention () DNA polymerases are more effective. Similarly, acyclovir is phosphorylated by herpes thymidine nucleoside kinase to form a cycline monophosphate (Ucycl-oguanosine) monophosphate * which is then phosphorylated by the host to form a guanine nucleus Glycoside triphosphate. This derivative is a more potent viral polymerase inhibitor than human DNA polymerase. In these cases, the drugs used for viral replication are sufficient to ensure that they do not cause excessive toxicity by inhibiting the host DNA polymerase. Papilloma virus re-cracking cannot be selectively inhibited, because when infected with papillary stag virus, no viral protein has been found to have DNA polymerase activity. In addition, recent studies of HPV replication in cell-free processed systems have shown that HPVs use one- or multi-host polymerase for replication. Guo (Kuo> et al., 269 J. Biol. Che .. 24058-65 (1994). The authors pointed out that when using knock-11 replication to ^^ effective replication will depend on the viral proteins E1 and E2, human polymerase- , The replication protein Ν ^> A and isomerase I and I. There are many kinds of treatments to treat HPV infection. The antimitotic drug Condylox (Condylox) can be used for local treatment of exogenous genital warts. However According to the reference manual of the 緳 师, about 65% of patients in the road bed test will have local adverse reactions such as: pain, itching, burning sensation, inflammation, hemoptysis or ulcer «1. In addition, Mydilos cannot be used to treat the anus Or mucosal warts. Injecting interferon-α and laser surgery in the affected area can also be used to treat papillomavirus infections. However, the second treatment is painful, expensive, and has a high recurrence rate. Another disadvantage of these methods It must be performed by a physician. If there is a drug that can be applied to the patient's body or external damage, it will be more advantageous than the existing treatment. Fidecoline (tetradecane-3,9-dihydroxy-4, lib-dimethyl-8, 11a This paper scale is applicable to China National Standards (CNS) A4 specification (210X 297 mm) (please read the notes on the back to write this page) ir * 06878 V. Description of invention () A7 B7 Printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economics-methylene-llaH- Can Geng [α] naphthalene-4,9-dimethyl enzyme) is an antibiotic produced by Cepha I ospor iu · aphidicola, which is a powerful inhibitor of cellular DNA synthesis. This effect is attributed to Inhibition of DNA polymerase in dairy animals. Specifically, Fideco_ can inhibit the activity of eukaryotic DNA polymerase-α, δ, and €. Fidecoline can also be used in group food and rabbit eyes Inhibit the replication of herpes simplex virus (hereinafter referred to as "HSV"). This effect even appears in mutant mules that have developed resistance to other antiviral thins, such as: HSV mutations resistant to phosphorous carboxycarboxylic acid. In addition, it has been confirmed that phendicoline can inhibit the virus polymerase produced by HSV and vaccine viruses. Although phendicoline has strong antiviral activity, it has not seen its use in pancreatic therapy. In particular, there are several The problem of children hindered the antiviral therapy First, the oral administration of burial site is not bioavailable. Second, phendicoline is difficult to dissolve in water, so a large amount of liquid must be injected during systemic treatment. This problem is due to the development of water solubility The burial site of porphyrin (phendicoline glycinate) has to be solved. When encountering phendicoline for medical purposes, another problem is that when the systemic drug is administered, the host DNA is suppressed. Toxicity caused by polymerase. Sessa et al. Found a dose-limiting local toxicity and neurological symptoms in the phase I clinical trial of corycoline glycinate in the burial site of patients with ovarian cancer. Hisa et al., 83 J. Natl. Cancer Institute 1160-64 (1991). The author pointed out in the conclusion that the clinical development of phendicoline glycinate should be directed to the study of the combination of the medicaments and the clinically approved anti-hypertensive "cisplatin". The literature is the same as above. Post later, please read the note on the back ιδ%

L The size of the revised paper is applicable to the Chinese National Standard (CNS) A4 specification (210X297mm) 6 A7 B7__ 5. In the literature of invention (), Damia < Da «ia > and others have discussed this combination It has the effect of mice with reticular cell paralysis. Feng Yami et al., 30 Cancer Che ^ other · Phariacol. 459-464. Among them, the intermediate effect of Shipladin activity was observed, but it did not support the bed use of the combination of Fidecoline Glycinate and Shipulidine. The literature is the same as above. There is also no indication that topical application of the burial site of corroline can treat viral infections. The present invention provides a thin topical formulation containing phendicoline or its derivatives for the treatment of viral infections. The basis of the present invention is to find that phendicoline and its prodrugs are likely to have excessive toxicity when administered systemically, but the drug can be effectively used as a local antiviral therapeutic agent. The formulations of the present invention, which are acceptable for topical use on B, contain fendico or its derivatives. As used below, the term "burial placencoline" is defined to include phendicoline derivatives having DNA polymerase inhibitory activity. The concentration of phendicoline must be sufficiently high enough to allow burial of colicin to enter the cell and inhibit the DNA polymerization_activity required for viral replication. In one embodiment, the concentration of phendicoline is sufficient to inhibit the host polymerase. In a better formulation for the treatment of Piru papillary nipple virus infection, the concentration of fidelicoline is sufficient to inhibit eukaryotic DNA polymerase-cl, δ and €. In another specific example, the concentration of burial site is sufficient to inhibit viral polymerase. This specific example applies to the treatment of viruses such as HSV-1 and HSN-2. The carrier of the present invention may be any pantologically acceptable carrier for peripheral use. Suitable mounting surfaces include liquid matrices, gels, aerosols, powders, pastes, creams, softeners, and lipase / propylene glycol (FAPG) substrates. The preferred loading surface contains the paper standard, and the Chinese National Standard (CNS) Α4 specification (210 X 297 mm) is applicable. V. Description of invention () A7 B7 DMSO, polyalkylene disulfide printed by the Employee Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Fermented and fermented liquid preparations. The present invention also provides a method for the local treatment of viral infections, which comprises topically applying a panax formulation containing phendicoline to the skin of a virus infected skin. The topical formulation is preferably applied twice a day. In some cases, the treatment can be built once to heal. However, the course of treatment is mainly for a long time of at least about 7 days. In addition, treatment can be continued for a period of time after damage symptoms disappear to prevent recurrence. When the present invention is compared with the current methods for treating genital warts, the superiority of the present invention is easy to see. The topical formulation of the present invention is different from the currently used genital warts topical therapy, and does not produce any adverse effects on the temporal crust. In the bedbed test of topical phendicoline formulations, most patients indicated that the pain and itching associated with infection had decreased. In addition, the treatment of the present invention is the opposite of interferon injection method and laser surgery in the affected area, and the patient can treat himself at home. The basis of the present invention is to find that the burial site of coline and its derivatives are suitable for the local treatment of viral infections. The burial site Corioline is a virus and eukaryotic DNA polymerase (including human DNA polymerase-〇_, 8 and €) that strongly suppresses rain. Because this effect affects human polymerase, the use of Fideco_ as a systemic B agent has not been successful. It has been found that local medicinal preparations can be used to allow effective phendicoline or phendicoline derivatives to enter virus-infected cells without causing systemic toxicity. As mentioned above, the term "phendicoline" includes phendicoline derivatives such as, for example, prodrugs that can be converted into phendicoline within the sickle (intracellular or extracellular). Examples of prodrugs include one of which has been modified into esters by polyhydric hydroxyl groups, _ Please read the precautions first. The paper size is applicable to the Chinese National Standard (CNS) A4 specifications (210X297 mm) 8 Α7 Β7 306878 V. Description of the invention () Or iodate derivatives * etc. Fidecoline glycinate is an example of a vinegar derivative suitable for the present invention. The present invention provides a topical formulation containing phendicoline in a suitable topical agent. The concentration of phendicoline should be close enough to inhibit DNA polymerization activity in cells when the formulation is applied to the site infected with the virus. The present invention also provides a method for treating dermatoses * infections, which comprises administering a topical β-drug formulation containing phendicoline to the infected site. Masaimayi The topical formulation of the present invention can be used to treat skin infections caused by any virus that requires eukaryotic polymerase-〇_, δ, and / or € for viral replication (e.g., papillary epilepsy virus). In addition, because phendicoline also inhibits viral DNA polymerase, topical formulations can be used to treat herpesviruses * such as HSV-1 and HSV-2 skin infections. Miscellaneous extracts for painful areas are supplied with M8R preparations. The formulation of the present invention contains bursacolide in a topical carrier that is acceptable on the surface. The concentration of the burial site must be sufficient to allow the inhibitory concentration of phendicoline to be delivered to the cells infected with the virus * that is, there must be a sufficient amount of phendicoline to enter the cell to inhibit the DNA polymerization of the diseased replication Enzyme activity. In the treatment of papillomavirus infection, the concentration of cullin in the cells must be sufficient to inhibit the host DNA polymerase. In one embodiment, the concentration of phendicoline can inhibit the host polymerase-〇_, J and €. Generally, the concentration of phendicoline depends on the specific virus infection, ranging from about 1 wM (0_34 mg / ml) to about 15 · M (5.10 mg / ml). For example: Concentration model suitable for the treatment of papillary echinovirus infection. The paper size is applicable to China National Standard (CNS) Α4 specification (210Χ297mm) (please read the notes on the back to fill in this page)

L, τ printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 9 306878__ V. Description of the invention () 醑 is about 1 // M (0.34 g / ml) to about 1 · M (0.34 mg / ml). Preferably, the concentration of phendicoline is between about 50 WM (17 withdrawals / ml) to about 800 wM (0.27 mg / * l), and even more preferably, it is about 100 // M (34 chokes / « L) to 500 «M (0.17 mg / ml). However, the appropriate concentration of fidecoline can depend on the specific viral infection to be treated. For example, when treating HSV-1 and HSV-2, a concentration of fidelicoline up to 15 bM (5.10 mg / ml) can be used. The most appropriate amount of infection for a particular virus can be determined by relevant experts. The carrier can be any buccal acceptable topical carrier. Many of these carriers are known to those who choose the appropriate carrier based on the particular substance and application site. Suitable carriers include liquid, gel, aerosol, powder, paste, cream, soft bud, and lipase / malonase (PAPG) and other substrates. The printing liquid of the Beigong Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs "The blue orchid can contain glycerin, polyethylene glycol, hexane-1,2,6-triester, polyethylene yeast, laurel yeast, nutmeg yeast, whale yeast , Stearase, oleaginous, lanolin, anhydrous lanolin, lanolin derivatives, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, cholesterase, ethanedase and / or propylene Di-enzyme monosaccharides, glyceryl monoesters, self-emulsifying glyceryl monostearate, sorbous and / or sorbous liver vinegar, vegetable oil, sulfated oil, isopropyl myristate, isocyanurate C_, and so on. Suitable polymers for the gel matrix carrier include, for example: tragacanth, staghorn, pectin, agar, medicinal acid, methyl oretin, hydroxyethylferroside, hydroxypropyl methylcellulose , Carboxymethyl ferrovitamin, bentonite, magnesium aluminum silicate, 1aponite, carbopol (carboxyvinyl polymer laid with allyl sucrose), and combinations thereof. This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X 297mm) -10 10 B7 5. Description of the invention () Suitable aerosol carriers include ··· Solution aerosol, powder aerosol, emulsion aerosol and Semi-solid aerosol. The powder base carrier may include zeolite, zinc oxide, starch, kaolin, and the like. Suitable pastes can contain many formulas in fat matrices such as: zinc oxide, starch, calcium sulfonate, talc, hydroacid, and dihydroxyphenol. The cream can be a water-in-oil or oil-in-water emulsion. Suitable ointments may include hydroxy, fat and fixed oil bases, silicones, absorbent bases, emulsified bases, water-soluble bases, and the like. The carrier can also be FAPG based, including for example: stearyl alcohol, malonylase, polyethylene glycol and glycerin. When the topical formulation contains a mixture of incompatible fluids, the formulation may contain an interfacial agent, and K forms a uniform stabilizer. Examples of suitable surfactants include: alkyl broken esters, glyceryl monostearate, polyoxyethylene sorbitan liver monostearate and monooleate (polysorbate 80), and polyethylene glycolic acid . Other widely used for the preparation of topical preparations include palmetate whale caviar and phase R esters that can improve the firmness of the cream; hard acid and stearase, can be used as lubricating thin, softening and defoaming fit; and methyl ore vitamin and yellow gum, used as a floating agent in the paste ointment. Any such additives can be included in the topical formulations of the present invention. Finally, the topical formulation may also contain preservatives such as, for example, p-aminobenzoic acid methyl acetate and propionyl (methyl and propyl-paraben (par.abe.n)) η test when filling with HI Dong ’s factors include: the solubility and stability of the medical agent in the carrier, the ability of the carrier to promote penetration, and the chemical and physical interaction of the carrier and the stratum corneum. The present invention includes phendicoline floating liquid, so phendicoline can be used in local formulations, which is quite insoluble in this paper. The Chinese standard (CNS) A4 specification (210 X 297 mm) is applicable. 11 A7 B7 V. Description of the invention (where the load is thin. However, it is usually better to dissolve the burial site of porphyrin. The burial site should be in the period of phendicoline treatment (mainly about 8 to 18 hours) Maintain long-term stability. Fidecoline is best kept in the vehicle for at least about 2 years. The formulation can be stored in the refrigerator (about 4¾) to enhance stability. In an embodiment of the embedding, loading and The horny layer is hydrated, thus promoting the penetration of Fidecoline. In addition, the contained content of "It is best to reduce the resistance of the infected site. The topical formulation of the present invention does not have to be free. However, M sterile formulation Preferably, the carrier is preferably sterile or can be sterilized after being combined into a topical formulation. The topical formulation can be killed by any conventional method that does not break the soil, phendicoline or carrier. Suitable sterilization methods include Filtration and irradiation. In addition, it can be formulated as described above Contains anti-corrosion, Μ reduces or prevents bacterial pollution. In a specific example, contains _ contains dimethyl sulfoxide (DMSO). A variation of this embodiment is warfare. In addition to DMSO, it also contains Polyalkylene diacid and one kind of enzyme. The other changes are contained in about 55; DMSO, about 45X polypropylene glycol, and about 503: B. Another item provides sustained release of phendicoline In a specific embodiment, the carrier contains a milk tank, including stearase and whale fermentation. A variation of this brewed embodiment is that the milk tank still contains malonylase and polyethylene glycol-100 (PEG-100) Stearic acid is cool. In another thrashing change, the cream contains 253L stearase, 252 whale fermentation, 12X malonase, 105; PEG-100 stearate, 7.96X polysorbate 60, 55: Yamanashi Sugar alcohol liver monostearate, glyceryl stearate, 5: Ιί material oil This paper standard is applicable to the Chinese National Standard (CNS) A4 specifications (210X 297 mm) Please read the back notes #-i Order 12-A7 B7 i, Invention Description (, 5X steamed water, 0.025X methylparaben And 0.015¾ propylparaben. The technique of combining «I ingredients and active ingredients is known to the art, and their methods applicable to the present invention are not different from the previous techniques. The treatment of dysentery _ At the site of infection, mainly referring to the skin lesion, apply the topical pancreatic compound formulation of the present invention to treat the skin segment virus infection. Any conventional applicator such as plum ball can be used to administer the formulation. The best applicator is It is non-condensing. The most appropriate course of treatment may vary depending on the type and location of the virus infection; however, it is usually given twice a day to provide good results. Therefore, topical formulations are mainly applied once in the early exhibition. Apply again at or near the morning. The formulation is usually applied for at least 7 consecutive days, or preferably until any symptoms of damage disappear. In addition, after the damage symptoms disappear, treatment can be continued for a period of time to prevent recurrence. When treating skin damage, local preparations are applied directly to the affected area. For example, when the damaged site is about 1 inch in diameter, the topical formulation is applied to the endothelium around 1/2 of the damaged site. In one embodiment, the method is used to treat genital warts caused by papilloma virus. Therefore, the topical formulation is applied directly to any wart and its surrounding skin. Both endogenous and exogenous damage can be treated in this way. In other examples of embedding, this treatment is used to treat HSV-1 and HSV -2 °. The following clear but non-limiting examples further illustrate the invention. The crack process described in the present mode can be actually operated, and the process described in the past mode is the process carried out by the laboratory. Please read the back-ordered version of the paper printed by the Employees Consumption Cooperative of the Central Ministry of Economic Affairs of the Ministry of Economic Affairs. The standard of the paper is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 13-13 B7 1 'invention description () 富 例 1_ 雎 床The test carried out the bed test of the present invention. 40 female patients were tracked. The age of the patients was from 22 to 50 years old. All patients received topical treatment with phendicoline formulations, once in the morning and once in the morning. Μ 梅花 球 administer the formulation to the warts. 0 The formulation contains 100wM or 500wM Fideco, 5X DMS0, 45% propylene glycol and 50X ethylenic < v / v>. When preparing the formulation, take appropriate mixture of DMS0, malonylase and ethylenzyme. Add the solid phenanthroline to the mixture and stir overnight at room temperature * to ensure that the burial site is completely dissolved. Due to the high concentration of ethyl yeast in the formulation, it is not necessary to kill it. The results of each process are shown in Tables I and I, and are collectively shown in Table 1. Internal damage such as the labia minora, the vaginal vestibule, the genitals, and the perineum are externally damaged ("E"). They are equivalent to the anterior vaginal fornix, posterior vaginal fornix, vaginal wall, and vaginal neck. "1"). Du Printed by Employees' Consumer Cooperation of the Central Standards Bureau of the Ministry of Economy

A

7 B Printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economy V. Description of the invention () Table I. The effect of 500 W medicoline on genital warts

This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 15 V. Description of the invention (A7 B7 The Ministry of Economic Affairs Central Standards Bureau Employee Consumer Cooperative Printed a table E. 100 W M Fidecoline for the treatment of genital warts "Patient No. nr Pre-treatment time (months) EI 100% > 50% < 50% dosage 3 1 1 X 7 5 2 1 X 3 7 1 2 X 2 9 1 1 X 2 + 11 0 1 X 2 13 1 1 X 6 15 2 1 X 3 17 2 1 X 3 19 1 2 X 5 21 1 2 X 3 22 0 1 X 1 24 2 0 X 5 26 0 1 X 4 27 1 2 X 3 29 0 2 X 5 31 1 1 X 3 33 1 1 X 2 35 2 1 X 5 38 1 2 X 2 39 1 1 X 3 Please first: Read * Back Winter

I write the information on this page. The paper scale is applicable to the Chinese National Standard (CNS) Α4 specification (210Χ 297 mm) 16 ^ 06878 V. Description of the invention () A7 B7 Table 1. Comprehensive results of clinical trials. Results of the number of cases 100: £ Healing > 50Z Healing <505; Healing can be ignored 500 w Μ 20 3 (15%) 7 (35%) 10 (50%) 0 (0%) 100 / i Μ 20 0 (0¾) 9 (45¾) 7 (35%) 4 (202) Some patients have a burning sensation during the administration of the formulation. However, 80% of patients no longer feel pain and itching and yin excretion decreases. 100¾ The recovered patients no longer have warts after 2 months of treatment. _ i V ___T ^^^ 1 —ϋ— nn n · ^ n ^ ^^^ 1 i ^ n ml l0 '· :: i (please read the notes on the back of the page and write this page) Central Standard of the Ministry of Economic Affairs The size of the paper printed by the Bureau ’s Consumer Cooperatives is applicable to the Chinese National Standard (CNS) A4 (210X297mm)

Claims (1)

A8 δδ C8 D8 Application for Patent Scope No. 84106769 Application for amendment to the patent scope 'Date of amendment: A pharmaceutical composition for local treatment of viral infections of Piru in November 1985, which includes: (a) Fide Corioline or one of its derivatives at a concentration sufficient to inhibit the activity of one of the DNA polymerases selected from the host DNA polymerase, delta and e, and a viral DNA polymerase in the virus-infected site where the composition is administered; b) Pharmaceutically acceptable topical carriers. 2. The pharmaceutical composition according to item 1 of the patent application scope, wherein the composition contains phendicoline glycominate. 3. For the pharmaceutical composition according to item 1 of the patent application, where the concentration of phendicoline or the derivative is 1 μ Μ to 15 m Μ ° 4. For the pharmaceutical composition according to item 3 of the patent application, wherein The concentration of Fidecoline or the derivative is 50 μM to 800 μM. 5. The pharmaceutical composition as claimed in item 4 of the patent application, wherein the concentration of phendicoline or the derivative is 100 μM to 500 μM. 6. The pharmaceutical composition as claimed in item 1 of the patent application, wherein the carrier is pseudo-selected from the group consisting of liquid, gel, aerosol, powder, paste, cream, soft bud, and FAPG base. 7. The pharmaceutical composition according to item 1 of the patent application scope, wherein the carrier contains a surfactant. 8. The pharmaceutical composition as claimed in item 6 of the patent scope, wherein the carrier is a liquid brew containing DMSO: (CNS) A4 ^ ~ (210X297HT ---------- f-^ --- --- lsτ ------ ft shoulder two * (please read the precautions on the back before filling in this page) Printed Bag 306878 A8 B8 C8 D8 _ of the Ministry of Economic Affairs of the Ministry of Economic Affairs of the Ministry of Economic Affairs of China 9. If the pharmaceutical composition according to item 8 of the patent application, wherein the liquid skeleton still contains: (a) polyalkylene glycol; and (b) alcohol. 10. If the patent application item 9 of the pharmaceutical composition A composition, wherein the carrier is a liquid containing the following components: (a) 5% DMS0; (b) 45¾ polypropylene glycol; and (c) 50% ethanol. 11. For a pharmaceutical composition as claimed in item 6, Wherein the carrier is a cream containing stearyl alcohol and cetyl alcohol. 12. The pharmaceutical composition as claimed in item ^, wherein the cream still contains propylene glycol and polyethylene glycol-100 stearate. 13. For the pharmaceutical composition of claim 12 of the patent scope, where the carrier is a cream containing the following ingredients: (Please read the precautions on the back before filling in this )-Installed. Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (a) 25¾ stearyl alcohol; (b) 25¾ cetyl alcohol; (c) 12¾ propylene glycol; (d) 10¾ PEG-100 stearate; ( e) 7.96¾ polysorbate 60; (f) 5¾ sorbitan monostearate (g) 5¾ glyceryl stearate; (h) 5¾ mineral oil; (i) 5% distilled water; Λ this paper The scale is suitable for the family A. japonica () A4 specification (21Qx297 male thin) 00 78 6 Ο ABCD 々, patent application scope (j) 0.025% methyl paraben; and (k〆0.015¾ propyl paraben. 1 4. The medical composition as claimed in item 1 of the patent scope, in which the virus infection of the skin is infected with the Papillary Virus infection :: 1 5. The pharmaceutical composition as claimed in item 14 of the patent scope, The infection of papilloma virus will produce genital warts. 16. As in the pharmaceutical composition of the first patent application, the skin virus infection is pseudo-herpes virus infection. 1 7. As in the patent application of the pharmaceutical composition of the 16th Composition, wherein the herpes virus infection is pseudo-caused by a virus selected from HSV-1 and HSV-2 y III __ 1 ding c · ^ r C , (Please read the precautions on the back before filling in the purchase) Printed by the Consumer Labor Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297g)