HK1073788B - Medicament for the treatment of viral skin and tumour diseases - Google Patents

Description

Medicine for treating viral skin and tumor diseases

The present invention relates to a medical compound having the formula:

wherein R is₁Each independently of the others, is straight-chain or branched, saturated, mono-or polyunsaturated, optionally substituted C₁₁-C₂₁Alkyl, alkylene, or alkynyl groups, preferably C₁₁-C₁₅Alkyl, alkylene, or alkynyl radicals, especially C₁₁-C₁₃Alkyl, alkylene, or alkynyl radicals, especially C₁₃An alkyl group, and

R₂each independently of the others, is a straight-chain or branched C₁-C₈Alkyl, alkylene, or alkynyl groups, preferably C₁-C₆Alkyl, alkylene, or alkynyl radicals, especially C₂-C₄Alkyl, alkylene, or alkynyl radicals, especially C₃An alkyl group; - [ CH₂-(CH₂)_m-O]_n-H groups, wherein n ═ 1 to 10, preferably n ═ 1 to 5; m is 1 to 5, preferably m is 1 to 3,

-CH₂-[CH-(OH)]_p-CH₂-(R₃)]group, wherein R₃Are independently of one another hydrogen or hydroxy groups; p-1-7, preferably p-1-4; a pentose group or a hexose group,

as therapeutically active compounds, either alone or in combination with one or more other pharmaceutically active compounds, useful in the treatment of various viral skin and/or neoplastic diseases, in particular diseases caused by Human Papillomavirus (HPV) and/or herpes virus, as well as pharmaceutical formulations having a topical effect and methods of use thereof.

Papillomaviruses (HPV) are DNA viruses that infect epithelial cells in a variety of mammals, inducing uncontrolled cell proliferation. Papillomaviruses are of a very diverse variety and can infect humans and different species of animals. In this connection, all virus types can infect essential epithelial cells, remain in the cell as additional episomes, or integrate their DNA into the host genome.

It has long been known that papillomaviruses can cause genital warts (condyloma acuminata), common or flat warts, and degenerative papulosis in both men and women, as well as neoplasms in the cervical epithelium.

Depending on the method used, the detection rate for papillomaviruses can reach almost 100%. The major viruses found in warts or genital warts are HPV 6 and HPV 11 viruses. Since HPV 16 and HPV 18 are mainly found in malignant, desquamated cell cancers such as penile cancer or cervical cancer, HPV 16 and HPV 18 are generally considered to be associated with malignant HPV diseases.

Currently, the treatment of genital warts caused by human papillomavirus is mainly by physical methods. Such methods include surgical excision, electrocautery cauterization, cryosurgery, and laser treatment. Other medical treatments employ podophyllotoxin (podophyllin), 5-fluorouracil, bleomycin, interferon, Imiquimod, and the like.

Surgical treatment has the disadvantage of being unpleasant for the patient and may also lead to further infections. The topical therapies used to date have the risk of side effects due to the cytotoxic effect of the active compounds employed, or the potentiation of the cellular immune defence capacity, leading to local inflammation. This situation illustrates that the treatments possible so far are still unsatisfactory.

Furthermore, it is a fact that the recurrence rate in the case of warts and genital warts is high and the complete cure is only possible by a continuous and consistent treatment. For this reason, more reliable and less painful treatment methods are urgently needed.

In particular, the treatment of genital warts and other diseases caused by papillomaviruses requires a treatment that is easily available to the patient. For example, patients may self-apply to the affected area, giving good results in a short period of time, and have little to no side effects.

Herpes Simplex Virus (HSV) is a class of DNA viruses in the sub-family of α -herpes viruses that can be divided into two genera, HSV 1, which is called the oral virus strain; and HSV2, known as the germline virus strain. Herpes simplex virus may be in the form of a nucleocapsid, which penetrates into the nerve endings and uses the nerve axial flow to reach the ganglia to which it belongs. They can spread from herpes lesions by staining and dripping, or become chronic carriers of health. After the initial infection, the virus in the latent infected neurons can be activated again, with symptoms or without symptoms, due to the stimulation of fever, trauma, or radiation. This reactivation process is dependent in particular on the body defence conditions as a whole. Herpes simplex virus can cause neoplastic transformation of cells in animals and in cell culture. It is currently under discussion whether the interaction between herpes simplex virus type 2 and cervical carcinogenesis may involve human papillomavirus types 16 and 18.

EP 0087161 discloses the treatment of herpes virus infections with a mixture comprising: isopropyl myristate and a small amount of 4- { lower alkyl } -2, 6- (di-tert-butyl) phenol containing 2, 6- (di-tert-butyl) -4-hydroxytoluene or 4- (lower alkyl) -2, 6- (di-tert-butyl) phenol.

EP 0842660 describes a pharmaceutical composition for the treatment of genital warts caused by human papillomavirus. The composition contains catechol extracted from tea (Camellia sinensis ) extract, and mainly comprises the following components: (-) -Gallic acid epi Galla chinensis catechol ester, and can be made into ointment or suppository.

It is an object of the present invention to find further effective antiviral substances and agents which are suitable for the treatment of various viral skin diseases and/or tumor diseases caused by papillomaviruses and/or herpesviruses.

It has now been found, surprisingly, that medicaments containing a compound of formula (I) as active ingredient,

is suitable for treating viral skin diseases and/or tumor diseases.

The invention relates to medicaments containing a compound of formula (I) as active ingredient,

A-B

(I)

wherein A is a group of the following general formula (II):

wherein B is a group of the following general formula (III):

(-O-R₂)

(III)

and

wherein R is₁Each independently of the others is straight-chain or branched, saturated, mono-or polyunsaturated, optionally substituted C₁₁-C₂₁Alkyl, alkylene, or alkynyl groups, preferably C₁₁-C₁₅Alkyl, alkylene, or alkynyl radicals, especially C₁₁-C₁₃Alkyl, alkyleneOr alkynyl radicals, especially C₁₃An alkyl group, and

R₂each independently of the others, is a straight-chain or branched C₁-C₈Alkyl, alkylene, or alkynyl groups, preferably C₁-C₆Alkyl, alkylene, or alkynyl radicals, especially C₂-C₄Alkyl, alkylene, or alkynyl radicals, especially C₃Alkyl radical, - [ CH₂-(CH₂)_m-O]_n-H groups, wherein n ═ 1 to 10, preferably n ═ 1 to 5. m is 1 to 5, preferably m is 1 to 3,

-CH₂-[CH-(OH)]_p-CH₂-(R₃)]group, wherein R₃Are, independently of one another, hydrogen or a hydroxyl radical, p ═ 1 to 7, preferably p ═ 1 to 4, a pentose radical or a hexose radical.

In this connection, the radical R₁And/or R₂Each independently of the others being substituted by halogen, preferably fluorine and/or chlorine, or straight-chain or branched C₁-C₆Alkyl, alkylene, or alkynyl groups, preferably C₁-C₃Alkyl, alkylene, or alkynyl groups, particularly methyl.

In this connection, the group a in the compound (I) can be derived, for example, from caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid (caprylic acid), undecanoic acid, lauric acid (camphoric acid), tridecanoic acid, myristic acid (myristic acid), pentadecanoic acid, palmitic acid (palmitic acid), margaric acid, stearic acid (stearic acid), nonadecanoic acid, arachidic acid, heneicosanoic acid, oleic acid, linoleic acid, linolenic acid, and/or arachidonic acid; preferably derived from: caproic acid, caprylic acid, capric acid, camphoric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and/or arachidonic acid; particularly preferably derived from myristic acid.

The group B in compound (I) may be derived from: e.g. straight or branched C₁-C₈Alkyl alcohols, in particular ethanol, propanol, isopropanol, n-butanol, tert-butanol; particular preference is given to isopropanol, ethylene glycol, polyethylene glycol, glycerol, polyglycerol, monoPentoses, for example, arabitol, adonitol, and xylitol; or hexoses, such as sorbitol, mannitol and/or dulcitol. Preferably derived from ethanol, propanol, isopropanol, butanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, glycerol, polyglycerol, arabitol, adonitol, xylitol, sorbitol, mannitol and/or dulcitol.

Compound (I) is preferably isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, ethyl myristate, propyl myristate, butyl myristate, and/or ethyl oleate; in particular isopropyl myristate.

In another preferred embodiment, compound (I) is a hydrophobic compound. According to the present invention, hydrophobic compounds are considered to have a solubility in water of at most about 0.2 mg/ml, particularly at most about 0.1 mg/ml.

The medicament contains a compound of formula (I), for example at least about 5-75% by weight, preferably at least about 10-60% by weight, in particular at least about 25-55% by weight, especially at least about 35-50% by weight.

In this respect, the medicament of the invention may also contain one or more other pharmaceutically active compounds as a combined preparation for simultaneous, separate or interactive use. In this context, other pharmaceutically active compounds which can be used for the treatment of viral skin diseases and/or tumor diseases are preferably, for example, podophyllum peltate, 5-fluorouracil, bleomycin, interferon, or imiquimod, and/or mixtures thereof containing at least one catechol.

In a preferred embodiment, the other pharmaceutically active compound is an amphiphilic molecule, or an amphiphilic active compound. Such amphiphilic molecules, or amphiphilic active compounds, can be considered to consist of a polymer having two functional moieties, specifically a hydrophilic moiety and a lipophilic moiety. This property may be particularly advantageous for allowing the substance to penetrate the skin for improved results.

In this respect, the improvement may be, for example, a longer residence time at the desired site or a reduction in the amount of active compound.

In a further preferred embodiment, the further pharmaceutically active compound comprises at least one catechol of the formula (IV).

Wherein the content of the first and second substances,

R₃is-H and-OH, and

R₄is-H or a group of formula (V):

the catechol added thereto may be obtained synthetically or from natural sources. As natural sources there may be mentioned in particular tea plants. In this regard, the concentration of the natural ingredient may vary depending on the species and variety of the tree. In this respect, it is preferable to use catechol isolated from Camellia sinensis (Camellia sinensis), (Camellia asamicca), (Camellia aborheaa), Camellia sinensis (Camellia sinensis), or Camellia oleifera (Camellia oleosa). All parts of the tea tree, especially tea, can be used for the isolation of catechins. Preferably, catechol isolated from an extract of tea leaves is used.

The catechols employed in the present invention are preferably selected from: epicatechin, epicatechin gallate, and gallnut catechol esters, particularly, (-) -epicatechin gallate, (+) -epicatechin gallate, and (-) -gallnut catechol esters.

The catechol may be used alone or in a mixture of different components. The catechol content of the catechol mixture is approximately 2 to 20 wt.%, preferably 4 to 15 wt.%, particularly preferably 10 to 11 wt.%; the (-) -epicatechin gallate content is from about 2 to about 20 weight percent, preferably from about 5 to about 15 weight percent, and more preferably from about 5 to about 7 weight percent; the content of (-) -epigallocatechin gallate is about 1-25 wt%, preferably 3-15 wt%, particularly preferably 5-7 wt%; the (-) -epigallocatechin gallate content is about 40-75 wt%, preferably 57-67 wt%, and particularly preferably 61-66 wt%; the content of (+) -Galla chinensis catechol is about 0.05-5 wt%, preferably 0.1-1 wt%, particularly preferably 0.1-0.6 wt%; and/or (-) -gallic acid and catecholate content is about 0.5-20 wt%, preferably 1-10 wt%, especially 1-5 wt%.

In a preferred embodiment, the catechol mixture comprises (-) -epicatechol at a level of about 5.9 weight percent, (-) -epicatechol gallate at a level of about 12.6 weight percent, (-) -epicatechol catechol at a level of about 17.6 weight percent, (-) -epicatechol gallate at a level of about 53.9 weight percent, and/or (-) -epicatechol catechin at a level of about 1.4 weight percent. Such compositions are known under the trade name Polyphenon^®100。

In a particularly preferred embodiment, the catechol mixture comprises approximately 10.8% by weight (-) -epicatechol, (-) -epicatechol gallate, approximately 6.5% by weight, (-) -epicatechol catechol, approximately 9.2% by weight, and/or (-) -gallnut gallate, approximately 4.0%. Such compositions are known under the trade name Polyphenon^®E。

The medicaments according to the invention contain, for example, from about 1 to 30% by weight, preferably from about 2 to 20% by weight, particularly preferably from about 15 to 18% by weight, of catechol and at least from about 5 to 90% by weight, preferably at least from about 10 to 70% by weight, particularly preferably at least from about 25 to 60% by weight, in particular at least from about 35 to 50% by weight, of compound (I).

The pharmaceutical compositions containing one or more compounds of the invention are conveniently prepared and used in accordance with the methods well known in the art of pharmacy. For this purpose, the active compounds, together with suitable pharmaceutically acceptable auxiliary substances and carrier substances, are formulated into a pharmaceutical formulation suitable for the different indications and the site of administration. In this case, the drug is prepared so as to achieve the desired release rate in each case, for example, rapid accumulation, and/or delayed release or depot effect.

Conventional emulsion, gel, ointment, mixed cream, or amphoteric emulsion systems (water-in-oil and oil-in-water mixed phases), as well as liposomes and transfer bodies (transfersomes) or plasters; preferably ointments and creams; most preferably an ointment; is conventionally applied to the skin or mucosa. The active compound is preferably applied topically to the area of the skin or mucosa where the pathology or illness is occurring.

In addition to being known for use on the skin and/or mucous membranes, the following tailored pharmaceutical formulations can be administered topically and regionally: emulsion, cream, ointment, effervescent tablet, or suppository for genital tract, vagina, or rectum. Rectal capsules may also be prepared based on gelatin or other carrier materials. Suitable suppository-based quality hardening fats, e.g., Witepsol^®、Massa Estarium^®、Novata^®Cocoa butter, glycerin/gelatin paste, glycerin/soap gel, and polyethylene glycol.

Examples of suitable auxiliary and/or carrier substances are: sodium alginate, which can be used as a gelling agent for the preparation of suitable bases or cellulose derivatives, such as guar gum, xanthan gum; inorganic gelling agents such as aluminum hydroxide, or pozzolanic clays (bentonite), the term being thixotropic gel precursor; polyacrylic acid derivatives, e.g. Cafbopol^®Polyvinyl pyrrolidone, microcrystalline cellulose and carboxymethyl cellulose. Low-molecular-weight and high-molecular-weight amphoteric compounds, and also phospholipids, are also suitable. The gel may be an aqueous-based hydrogel, or a hydrophobic organogel, for example based on a mixture of low and high molecular weight paraffinic and petrolatum. For example, hydrophilic polymers may be prepared on the basis of high molecular weight polyethylene glycolsAnd (4) organic gel. These types of gels are all washable. However, the organogel is preferably a hydrophobic gel. Hydrophobic auxiliary substances and additives, such as vaseline oil, wax, oleyl alcohol, propylene glycol monostearate, and propylene glycol monopalmitate, are particularly preferred. Of course, skin sedatives and/or inflammation inhibitors known to the person skilled in the art can likewise be added, for example synthetically prepared active compounds and/or extracts extracted from medicinal plants and/or active compounds, in particular bisobolol and panthenol. Dyes, such as yellow and/or red iron oxide, and/or titanium dioxide, may also be added for the purpose of shading.

Emulsifiers for the preparation of various water-in-oil and/or oil-in-water emulsions can be used, anionic, cationic or neutral surfactants, for example alkali metal soaps, amine soaps, sulfocompounds, conversion soaps, higher fatty alcohols, partial fatty acid esters of sorbitan and also polyoxyethylene sorbitan, for example of the lanette type, wool wax, wool fat, or other synthetic products.

The ointments, creams or emulsions may be prepared from petrolatum, natural or synthetic waxes, fatty acids, fatty alcohols, fatty acid esters, such as monoglycerides, diglycerides, triglycerides, paraffin or vegetable oils, hydrogenated castor or coconut oil, lard, synthetic fats, such as synthetic fats based on caprylic acid, lauric acid, or stearic acid, such as Softisan ®, or triglyceride mixtures, such as Mygliol ®, all of which may be used as lipids, in combination with fats and/or oils and/or waxes.

For increasing the stability, for example acid and base solutions with osmotic activity, such as hydrochloric acid, citric acid, sodium hydroxide solution, potassium hydroxide solution, sodium bicarbonate, and buffer systems, such as citrate, phosphate, tris buffer or triethanolamine, can be used for adjusting the pH. Preservatives, for example methyl benzoate, or propyl benzoate (parabens) or sorbic acid, may also be added.

Pastes, powders and solutions, which may be mentioned, can be applied topically as additional materials. Due to the continuous application, pastes often contain hydrophobic and hydrophilic auxiliary substances, however, it is preferred that hydrophobic auxiliary substances contain a high proportion of solid constituents. To increase dispersibility, flowability and smoothness, and to prevent caking, the powder or topically applied powder may contain starches, such as wheat or rice starch; flame-dispersed silica or silica, which may also act as diluents.

Pharmaceutical forms can be produced according to the pharmaco-physiological principles known to the skilled worker, in case-appropriate pharmaceutical forms.

The medicament of the present invention preferably comprises about 35% by weight isopropyl myristate, about 15% by weight at least one catechol, about 24.5% by weight petrolatum, about 20% by weight waxy, about 5% by weight propylene glycol monostearate or propylene glycol monopalmitate, and about 0.5% by weight oleyl alcohol.

The medicaments and/or medicament metabolites of the invention may be used to treat viral skin and/or neoplastic diseases.

The term drug metabolite is understood to mean one or more compounds produced during use as a result of the biological metabolism of the drug. These metabolites may be intermediate metabolites produced by intermediate metabolic processes, or end products of metabolism. Such metabolites are preferably those produced by dermal and/or mucosal applications, in particular hydrolysates of compounds of formula (I). Conceivable hydrolysates may be derived from the group a or the group B.

Viral skin diseases can be considered as benign skin diseases caused by viruses and/or associated viral infections. Including, for example, warts caused by papillomaviruses, genital warts, benign tumors of the skin and or mucosa. Such as plantar wart, verruca vulgaris, young verruca plana, epidermodysplasia verruciformis, condyloma acuminatum, verruca plana, anaplastic papulosis, laryngeal and oral mucosal papillomas, focal epithelial hyperplasia, orolabial herpes, kaposi's sarcoma, varicella and shingles.

These viral skin and/or tumor diseases may be caused by at least one papillomavirus or viruses, in particular human papillomaviruses, such as, for example, HPV1, 2, 3, 4, 5, 6, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19-29, 31, 32, 34, 36-38, 46-50, 56, 58; caused by at least one herpes virus or various herpes viruses, for example, herpes simplex virus 1, herpes simplex virus 2, varicella zoster virus or human herpes virus, for example 1, 2, 3, 4, 7 or 8.

The figures and the following examples are intended to illustrate the invention, but not to limit it. It will be within the ordinary skill of those in the art to make modifications to the invention without departing from the scope of the invention.

Examples

Clinical study comparing ointment and cream formulations containing isopropyl myristate

93 patients (divided into male and female facies groups) participated in a multi-center clinical study conducted in a total of 30 different centers in Germany and Russian. The study was performed as a randomized double-blind approach. This study examined the clinical efficacy of isopropyl myristate in two different formulations (an ointment and a cream) for external genital warts.

The components of the groups of the two formulations tested are shown in the table below;

cream 1:

material composition	Amounts (in%) by weight
		White beeswax	6.996
Monomuls	2.798
		Lamform TGI	5.598
Cetiol V	6.996
		Myristic acid isopropyl ester	13.992
Tocopherol	0.699
		Controx KS	0.066
Glycerol	6.996
		Ethylenediaminetetraacetic acid sodium salt	0.001
Magnesium sulfate	1.399
		D-panthenol	0.699
Pure water	53.678
		Ferrite red	0.025
Ferrite yellow	0.054

Note: the addition of such dyes is to perform shade matching.

Ointment 1:

material composition	Amounts (in%) by weight
		White oil, United states pharmacopoeia	34.023
White wax, NF	25.000
		Isopropyl myristate NF	35.000
Oleyl alcohol, NF	0.500
		Propylene glycol monostearate, NF	5.000
Ferrite red	0.022
		Ferrite yellow	0.055
Titanium dioxide, United states Pharmacopeia	0.400

Note: the addition of such dyes is to perform shade matching.

Patients applied the study drug topically 3 times a day, either until the genital warts were completely healed, or up to 12 weeks.

The data collected during the study were as follows:

complete cure (in%)

Sex of patient	Cream 1	Ointment 1
			For male	39.1	42.1
Woman	35.0	33.3

Partial cure (in%); this corresponds to a healing area of at least 75% of the total area of the genital warts.

Sex of patient	Cream 1	Ointment 1
			For male	43.5	63.2
Woman	50.0	52.4

The results of this study show that the high degree of complete or partial healing is surprising, and that the rate of spontaneous genital wart regression is about 20% in women and about 5% in men (Aldara) compared to placebo values obtained from similar studies with different formulations^TM(Imiquimod) cream, 5% product monograph, sold by 3M pharmaceuticals of quischi, california, Beutner KR et al (1998) j.am.acad.dermotol.38, 230-9; edwards L et al (1998) Arch.Dermatd.134 (1); 25-30).

This therapeutic effect is attributed to the action of isopropyl myristate, thus demonstrating for the first time its antiviral effect.

Clinical study comparing ointments and creams with isopropyl myristate and Polyphenon ® E

A multicenter study was conducted on 272 patients (equal groups of men and women in various cases) in germany and russia for a total of 30 different centers. The study examined the clinical efficacy of two different formulations (ointment and cream) of isopropyl myristate and Polyphenon ® E, in both randomized and double-blind forms. And in contrast to the external genital wart treatment of the preparation containing isopropyl myristate of example 1.

The components of the formulations containing Polyphenon ® E tested were as follows:

and (3) cream 2:

material composition	Amounts (in%) by weight
		Polyphenon®E	10.000
White beeswax	5.263
		Monomuls	2.105
Lamform TGI	4.211
		Cetiol V	5.263
Myristic acid isopropyl ester	10.526
		Tocopherol	0.526
Controx KS	0.050
		Glycerol	5.263
Ethylenediaminetetraacetic acid sodium salt	0.001
		Magnesium sulfate	1.053
D-panthenol	0.526
		Pure water	55.213

Ointment 2:

material composition	Amounts (in%) by weight
		Polyphenon®E	15.000
White oil, United states pharmacopoeia	24.500
		White wax, NF	20.000
Isopropyl myristate, NF	35.000
		Oleyl alcohol, NF	0.500
Propylene glycol monostearate, NF	5.000

Patients applied the study topically 3 times a day, either until the genital warts were completely healed, or for up to 12 weeks.

The data collected in the study were as follows:

complete cure (in%)

Sex of patient	Cream 1	Cream 2	Ointment 1	Ointment 2
					Male sex	39.1	53.9	42.1	61.0
Female with a view to preventing the formation of wrinkles	35.0	39.5	33.3	56.8

Partial cure (in%; 75%)

Sex of patient	Cream 1	Cream 2	Ointment 1	Ointment 2
					For male	43.5	64.2	63.2	80.5
Woman	50.0	47.4	53.4	81.1

Analysis of this study showed that isopropyl myristate in combination with Polyphenon ® E resulted in a surprising increase in the efficacy of this drug when comparing ointment 1 to cream 1 on the one hand and ointment 2 to cream 2 on the other hand.

If the ointment 2 is compared with the cream 2, the effect of the ointment 2 is proved to be obviously higher than that of the cream 2. This suggests that the hydrophobic ointment has a synergistic effect of Polyphenon ® E and isopropyl myristate.

Due to this synergistic effect, the amount of active compounds in the preparation is greatly reduced compared to the corresponding compounds in order to achieve the same effect. Thus, the use of such synergistic formulations has advantages not only in terms of efficacy, but also in terms of the cost of manufacture thereof, and thus, may play a positive role in the cost of treatment of patients.

Claims (35)

1. A medicament containing a compound of general formula (I) and at least one catechol of general formula (IV) as pharmaceutically active compounds of the medicament,

A-B

(I)

wherein A is a group of the following formula (II),

and

wherein B is a group of the following formula (III):

-O-R₂

(III)

and

wherein R is₁Independently of one another, is pentyl, heptyl, nonyl, straight-chain or branched, saturated, mono-or polyunsaturated C₁₁-C₂₁Alkyl, alkylene, or alkynyl, said R₁By halogen, straight or branched C₁-C₆Alkyl, alkylene, or alkynyl groups are substituted or unsubstituted,

and

R₂independently of one another, straight-chain or branched C₁-C₈Alkyl, alkylene, or alkynyl, said R₂By halogen, straight or branched C₁-C₆Alkyl, alkylene, or alkynyl substituted or unsubstituted; - [ CH₂-(CH₂)_m-O]_n-H groups, wherein n ═ 1 to 10; m is 1-5, and m is a linear chain,

-CH₂-[CH-(OH)]_p-CH₂-(R₃)]group, wherein R₃Independently of one another, hydrogen or hydroxy; p is 1-7; a pentose group or a hexose group; and in formula (IV)

R₃is-H or-OH and

R₄is-H or a group of formula (V)

And

the medicament contains at least 5-75% by weight of a compound of formula (I).

2. The drug of claim 1, wherein the group R is₁And/or the radical R₂Independently of one another by halogen or C₁-C₃Alkyl, alkylene, or alkynyl substitution.

3. The drug of claim 2, wherein the group R is₁And/or the radical R₂Independently of one another by methyl.

4. The drug of claim 1 or 2, wherein R is₁Independently of one another are C₁₁-C₁₅Alkyl, alkylene, or alkynyl, said R₁By halogen, straight or branched C₁-C₆Alkyl, alkylene, or alkynyl groups are substituted or unsubstituted.

5. The drug of claim 4, wherein R is₁Independently of one another are C₁₁-C₁₃Alkyl, alkylene, or alkynyl, said R₁By halogen, straight or branched C₁-C₆Alkyl, alkylene, or alkynyl groups are substituted or unsubstituted.

6. The drug of claim 5, wherein R is₁Is C₁₃Alkyl, alkylene, or alkynyl, said R₁By halogen, straight or branched C₁-C₆Alkyl, alkylene, or alkynyl groups are substituted or unsubstituted. C₁₃An alkyl group.

7. The drug of claim 1 or 2, wherein R is₂Independently of one another are C₁-C₆Alkyl, alkylene, or alkynyl, said R₂By halogen, straight or branched C₁-C₆Alkyl, alkylene, or alkynyl substituted or unsubstituted; - [ CH₂-(CH₂)_m-O]_n-H groups, wherein n ═ 1 to 5, m ═ 1 to 3;

-CH₂-[CH-(OH)]_p-CH₂-(R₃)]group, wherein R₃Independently of one another, hydrogen or hydroxy; p ═ 1-4, pentose groups or hexose groups.

8.The drug of claim 7, wherein R is₂Independently of one another are C₂-C₄Alkyl, alkylene, or alkynyl, said R₁By halogen, straight or branched C₁-C₆Alkyl, alkylene, or alkynyl groups are substituted or unsubstituted.

9. The drug of claim 8, wherein R is₂Is C₃An alkyl group.

10. The medicament of claim 1, which comprises at least 10 to 60% by weight of the compound of formula (I).

11. The medicament of claim 10, which comprises at least 25 to 55% by weight of the compound of formula (I).

12. The medicament of claim 11, which comprises at least 35 to 50% by weight of the compound of formula (I).

13. The medicament according to claim 1 or 2, wherein the radical R1 is undecyl, tridecyl, pentadecyl, heptadecyl, heptadecenyl, heptadecadienyl, heptadecatrienyl and/or nonadecatetraenyl.

14. The medicament according to claim 1 or 2, characterized in that the group B is chosen from: ethoxy, propoxy, isopropoxy, hydroxyethoxy, poly (oxyethylene), 3-hydroxy-propoxy, poly (oxypropylene), 2, 3-dihydroxypropoxy, poly (oxy-2-hydroxy-propylene), (2S, 3R, 4R) -tetrahydroxy-pentoxy, (3R, 3R, 3R) -tetrahydroxy pentoxy, (2R, 3R, 4R, 5R) -pentahydroxy-hexoxy, (2S, 3S, 4R, 5R) -pentahydroxy-hexoxy and/or (2R, 3S, 4S, 5R) -pentahydroxy-hexoxy.

15. The pharmaceutical according to claim 1, wherein compound (I) is isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, ethyl myristate, propyl myristate, butyl myristate, and/or ethyl oleate.

16. The medicament of claim 1, wherein the catechol is selected from the group consisting of: epicatechin, epicatechin gallate, and epicatechin gallate.

17. The medicament according to claim 16, wherein said catechol is selected from the group consisting of (-) -epicatechol, (-) -epicatechol gallate, (+) -gallocatechin, and (-) -gallnut gallate.

18. The medicament according to claim 1, wherein the catechins are present in a mixture comprising from 2 to 20% by weight of epicatechin; the epicatechin gallate content is 2-20 wt%; (-) -epicatechin content of 1-25% by weight; the (-) -gallic acid epigallocatechin content is 40-75 wt%; the content of (+) -Galla chinensis catechol is 0.05-5 wt%; and/or (-) -gallic acid catechin ester form 0.5-20 wt%.

19. The medicament according to claim 1, wherein the catechins are present in the form of a mixture containing 10.8% by weight of (-) -epicatechol, (-) -epicatechol gallate 6.5% by weight, (-) -epicatechol catechol 9.2% by weight, (-) -epicatechol gallate 54.8% by weight, and/or (-) -epicatechol gallate 4.0%.

20. The medicament of claim 1, wherein the catechol is isolated from an extract of tea leaves.

21. Pharmaceutical according to claim 1, characterized in that the preparation contains 1-30% by weight of catechol, and at least 5-90% by weight of compound (I).

22. The medicament of claim 1, wherein the pharmaceutically active compound is a hydrophobic compound.

23. The medicament of claim 1, further comprising additives and/or auxiliary substances.

24. Pharmaceutical according to claim 23, characterised in that the additive and/or auxiliary substance is hydrophobic.

25. The pharmaceutical of claim 24, wherein the additives and/or auxiliary substances are selected from the group consisting of petroleum jelly, wax, oleyl alcohol, propylene glycol monostearate and propylene glycol monopalmitate.

26. A pharmaceutical composition comprises 35 wt% isopropyl myristate, 15 wt% at least one catechol, 24.5 wt% petrolatum oil, 20 wt% wax, 5 wt% propylene glycol monostearate or propylene glycol monopalmitate stearate, and 0.5 wt% oleyl alcohol.

27. Use of a medicament according to claim 1, and/or a drug metabolite thereof, for the manufacture of a medicament for the treatment of viral skin and neoplastic diseases.

28. The use of the medicament according to claim 27 for viral skin and/or tumor diseases caused by papillomaviruses, herpesviruses, varicella zoster or human herpesviruses.

29. The pharmaceutical use of claim 28, wherein the papillomavirus is a human papillomavirus.

30. The pharmaceutical use of claim 29, wherein the human papillomavirus is HPV1, 2, 3, 4, 5, 6, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19-29, 31, 32, 34, 36-38, 46-50, 56, 58.

31. The use of claim 30, wherein the herpesvirus is herpes simplex virus 1, herpes simplex virus 2, varicella zoster virus or human herpesvirus 1, 2, 3, 4, 7 or 8.

32. The pharmaceutical use according to claims 27-31, wherein the skin disease caused by papillomavirus is warts, genital warts, benign tumors of the skin and/or mucous membranes.

33. The use of claim 32, wherein the skin disorder caused by papillomaviruses is plantar warts, common warts, young verrucas, epidermodysplasia verruciformis, condyloma acuminatum, flat warts, anaplastic papulosis, papillomas of the laryngeal and oral mucosa, focal epithelial hyperplasia, orolabial herpes, hemorrhagic sarcoma of the skin (kaposi's sarcoma), varicella and/or shingles.

34. Use of a medicament according to claim 1 for the preparation of a medicament for topical application.

35. The use of claim 34, wherein the topical application is selected from the group consisting of genital tract or vaginal topical application.