Medicinal agent for treatment of viral cutaneous and tumor diseases

FIELD: medicine, pharmacology.

SUBSTANCE: invention relates to a medicinal agent used in treatment of warts. Proposed agent contains an active compound chosen from isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, ethyl myristate, propyl myristate, butyl myristate and/or ethyl oleate and at least a mixture containing (-)-epicatechol, (-)-epicatechol gallate, (-)-epigallocatechol, (-)-epigallocatechol gallate, (+)-gallocatechol and (-)-gallocatechol gallate possessing the enhanced effectiveness.

EFFECT: valuable medicinal properties of drug.

7 cl, 2 ex

 

The present invention relates to a medicinal product, which contains a compound of the formula

where R1independently from each other, represents an unbranched or branched, saturated, mono - or polyunsaturated, optionally substituted C11-C21alkyl, alkalinity or alkynylaryl radical, preferably11-C15alkyl, alkalinity or alkynylaryl radical, in particular With11-C13alkyl, alkalinity or alkynylaryl radical, especially With13alkyl radical, and

R2independently from each other, represents an unbranched or branched C1-C8alkyl, alkalinity or alkynylaryl radical, preferably1-C6alkyl, alkalinity or alkynylaryl radical, in particular With2-C4alkyl, alkalinity or alkynylaryl radical, especially With3alkyl radical, a radical- (CH2-(CH2)m-O]n-H, where n = from 1 to 10, preferably n = 1 to 5, m = 1 to 5, preferably m = 1 to 3,

the radical-CH2-[CH(OH)]p- (CH2-(R3)], where R3independently from each other represents hydrogen or a hydroxyl radical, p = from 1 to 7, preferably p = 1 to 4, pentony radical or lexotnil radical,

as a therapeutically active compounds, separately or together with one or more additional pharmaceutically active compounds in the form of a combined preparation for the treatment of viral skin diseases and/or tumor diseases, which are caused in particular by the human papilloma virus (HPV) and/or herpes viruses, as well as locally acting pharmaceutical composition and its use.

The papilloma viruses (HPV) are DNA viruses that infect epithelial cells of mammals and, thus, induce uncontrolled cell growth. There is a very wide range of papilloma viruses, which infect humans and various animal species. In this regard, all viral types infect basal epithelial cells and remain as episome or integrate their DNA into the host genome.

For a long time it was known that the papilloma viruses cause genital warts (Condyloma acuminata), common and plantar warts, bowenoid papules men and women and intraepithelial lesions of the cervix in women.

Depending on the method used, the detection rate of HPV is almost 100%. In warts and genital-warts (Condyloma acuminata) are mainly viruses HPV 6 and HPV 11. Because HPV 16 and HPV 18 are found mainly in slocate the public squamous cell cancers, as it happens in case of penile cancer and cervical cancer, it is usually assumed that HPV 16 and HPV 18 are associated with malignant diseases HPV.

Currently, for the treatment of genital warts caused by human papilloma virus, are primarily used physical methods. These methods include surgical removal, electroacoustic, cryosurgery and laser therapy, but they are few. Additional medical treatment is the use of podofillina, 5-fluorouracil, bleomycin, interferon, imiqimod etc.

The disadvantage of surgical treatment is that it is very unpleasant for the patient and can lead to further infection. Up to the present time in the local treatment there was a risk of side effects, used as active compounds have cytotoxic properties or enhance cellular immune defense and may subsequently induce a local inflammatory reaction. This shows that therapeutic opportunities that were available up to the present time, are still not satisfactory.

In addition, the recurrence rate in the case of warts and genital warts are very high, and full recovery can be achieved only by long and persistent treatment. For this reason, there is a need for the more safe and comfortable treatment.

There is a need, especially in the treatment of genital warts, but also in connection with other diseases, which are caused by the human papilloma virus, the treatment, which is easily carried by the patient. For example, it would be appropriate treatment, which the patient can be carried out independently on the affected areas and which gives good results in a relatively short period of time and have only little or no side effects.

Herpes simplex viruses (HSV) is a DNA virus of the alpha subfamily Herpetoviridae. They are divided into two groups, ie, HSV 1, called oral strain, and HSV 2, called genital strain. Herpes simplex viruses penetrate into the nucleocapsid in the nerve endings and using axonal flow, reach their respective ganglia. They are smear and droplets of herpetic lesions or healthy chronic carriers. After primary infection, the virus can re-reaccelerates, symptomatically or asymptomatically by irritation due to, for example, fever, injury, or exposure of latently infected neurons. This reactivation depends, in part, from the protection status of the organism as a whole. Herpes simplex viruses can malignant transformed cells in the body tivotogo in cell cultures. Currently discussing the possibility of the relationship between herpes simplex virus type 2 and cancer of the cervix, which is attended by the human papilloma virus type 16 and type 18.

In EP 0087161 described the treatment of herpetic infections mixture consisting of isopropylmyristate and small amounts of 4-{lower alkyl}-2,6-(bis-tert-butyl)phenol, containing 2,6-(bis-tert-butyl)-4-hydroxytoluene or 4-{lower alkyl}-2,6-(bis-tert-butyl)phenol.

In EP 0842660 described pharmaceutical composition for the treatment of genital warts caused by human papilloma virus. Described composition contains category from extracts of tea (Camellia sinensis), mainly (-)-epigallocatechingallate, in the form of ointment or suppository.

The aim of the present invention, therefore, is the search for more effective antiviral substances and compositions that are applicable for the treatment of viral skin diseases and/or tumor diseases, which are caused by papilloma viruses and/or herpes viruses.

Currently, it has been unexpectedly found that the drug, which contains a compound of the present invention of formula (I) as pharmaceutically active compounds, is applicable for the treatment of viral skin diseases and/or tumor diseases.

Now the image is the group of thus, relates to a medicinal product, which contains a compound of the formula (I) as pharmaceutically active compounds,

where a represents a radical of the formula (II)

and represents a radical of the formula (III)

and

R1independently from each other, represents an unbranched or branched, saturated, mono - or polyunsaturated, optionally substituted C11-C21alkyl, alkalinity or alkynylaryl radical, preferably11-C15alkyl, alkalinity or alkynylaryl radical, in particular With11-C13alkyl, alkalinity or alkynylaryl radical, especially With13alkyl radical, and

R2independently from each other, represents an unbranched or branched C1-C8alkyl, alkalinity or alkynylaryl radical, preferably1-C6alkyl, alkalinity or alkynylaryl radical, in particular With2-With4alkyl, alkalinity or alkynylaryl radical, especially With3alkyl radical, a radical- (CH2-(CH2)m-O]n-H, where n = from 1 to 10, preferably n = 1 to 5, m = 1 to 5, preferably m = 1 to 3,

the radical-CH2-CH(OH)] p- (CH2-(R3)], where R3independently from each other represents hydrogen or a hydroxyl radical, p = from 1 to 7, preferably p = 1 to 4, pentony radical or lexotnil radical.

In this regard, the radical R1and/or the radical R2can be, independently of one another, substituted by halogen, preferably by fluorine and/or chlorine, or an unbranched or branched C1-C6alkyl, ulkelerinin or alkynylaryl radical, preferably With1-C3alkyl, ulkelerinin or alkynylaryl radical, in particular a methyl radical.

In this regard, the radical And the compound (I) can, for example, be obtained from hexanoic acid (Caproic acid), heptane acid, octanoic acid (Caprylic acid), nonanol acid, decanoas acid (capric acid), undecanoic acid, dodecanol acid (lauric acid), tridecanoic acid, tetradecanoic acid (myristic acid), pentadecanoic acid, hexadecanoic acid (palmitic acid), heptadecanoic acid, octadecanoic acid (stearic acid), nonadecanoic acid, eicosanol acid, heneicosanol acid, oleic acid, linoleic acid, linolenic acid and/or arachidonic acid, preferably, from Caproic acid, Caprylic acid, Aprilovo acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid and/or arachidonic acid, particularly preferably from myristic acid.

Radical In the compound (I) can, for example, be obtained from unbranched or branched C1-C8Olkiluoto alcohol, in particular ethanol, propanol, isopropanol, n-butanol, tert-butanol, particularly preferably from isopropanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropyleneglycol, glycerol, polyglycerol, pentoses sugar, such as Arabic, adonit and xylitol, or hexoses sugar, such as sorbitol, mannitol or dulcet, preferably from ethanol, propanol, isopropanol, butanol, ethylene glycol, polyethylene glycol, propylene glycol, polypropyleneglycol, glycerol, polyglycerol, Arabica, adonica, xylitol, sorbitol, mannitol and/or dulcita.

The compound (I)preferably represents isopropylene, isopropylmyristate, isopropyl, isopropylene, atelierista, profilerita, mutiliated and/or etiloleat, in particular isopropylmyristate.

In another preferred embodiment of the present invention the compound (I) is a hydrophobic compound. According to the present invention, the hydrophobic compound is meant a compound the solubility of which in water is at most about 0.2 mg/ml, in particular at most about 0.1 mg/ml

The medicinal product contains, for example, at least about 5-75 wt.%, preferably, at least about 10-60 wt.%, in particular, at least approximately 25-55 wt.% and especially at least approximately 35-50 wt.% the compounds of formula (I).

In this regard, the drug of the present invention may also contain one or more additional pharmaceutically active compounds in the form of a combined preparation for use simultaneously, separately or separated by time. In this context, preference is given to use as an additional pharmaceutically active compounds such compounds that can be used for the treatment of viral skin diseases and/or tumor diseases, such as podophyllum, 5-fluorouracil, bleomycin, interferon or imagined, and/or mixtures that contain at least one catechol.

In a preferred embodiment of the present invention additional pharmaceutically active compound is an amphiphilic or amphipatic active connection. Under amphiphilic or amphipatic active connection means active compounds which act which consists of two functional parts, in particular one hydrophilic part and one hydrophobic part. This property can, in particular, to facilitate the passage of substances through the skin and to achieve better effect. In this regard, the improved effect can be achieved, for example, over a long period of existence in the desired area or reducing the dose of the active connection.

In yet another preferred embodiment of the present invention additional pharmaceutically active compound contains at least one catechol of the formula (IV)

where

R3represents-H or-HE and

R4represents-H or a group of the formula (V)

Category that add in this regard, can be obtained synthetically or from natural sources. As natural sources can be specially mentioned the tea plants. In this context, natural ingredients can be present in various concentrations depending on species and variety. In this context, is used categoly it is preferable to select from Camellia sinensis, Camellia asamica, Camellia bohea, Camellia chinensis or Camellia oleosa. All components of the tea plants, particularly the leaves, can be used to highlight catecholo. Used to theholy preferably separated from the tea extract.

Used in the present invention categoly preferably represent epicatechol, epicatechol, epigallocatechol, epigallocatechingallate, gallocatechin and galactagogue, in particular, (-)-epicatechol, (-)-epicatechol, (-)-epigallocatechol, (-)-epigallocatechingallate, (+)-gallocatechin and (-)-galactagogue.

Category can be used both separately and in the form of mixtures with different composition. A mixture of catecholo contains about 2-20 wt.%, preferably, about 4-15 wt.%, in particular, approximately 10-11 wt.% (-)-epicatechol, about 2-20 wt.%, preferably, about 5-15 wt.%, in particular, approximately 5-7 wt.% (-)-epicatechol, about 1-25 wt.%, preferably, about 3-15 wt.%, in particular, approximately 5-7 wt.% (-)-epigallocatechol, approximately 40-75 wt.%, preferably, approximately 57-67 wt.%, in particular, approximately 61-66 wt.% (-)-epigallocatechingallate, about 0.05-5 wt.%, preferably, about 0.1-1 wt.%, in particular approximately 0.1 to 0.6 wt.% (+)-gallocatechin and/or about 0.5-20 wt.%, preferably, about 1-10 wt.%, in particular, about 1-5 wt.% (-)-allocationally.

In a preferred embodiment of the present invention a mixture of catecholo consists of rough is about 5.9 wt.% (-)-epicatechol, approximately 12.6 wt.% (-)-epicatechol, approximately 17.6 wt.% (-)-epigallocatechol, approximately 53,9 wt.% (-)-epigallocatechingallate and/or about 1.4 wt.% (-)-gallocatechin. The composition of the composition known under the trade name Polyphenon® 100.

In a particularly preferred embodiment of the present invention a mixture of catecholo consists of approximately 10.8 wt.% (-)-epicatechol, approximately 6.5 wt.% (-)-epicatechol, about 9.2 wt.% (-)-epigallocatechol, approximately of 54.8 wt.% (-)-epigallocatechingallate and/or about 4.0 wt.% (-)-allocationally. The composition of the composition known under the trade name Polyphenon® E.

The drug of the present invention contains, for example, about 1-30 wt.%, preferably, about 2-20 wt.%, and, in particular, approximately 15-18 wt.% of catechol and at least about 5-90 wt.%, preferably, at least about 10-70 wt.%, in particular, at least approximately 25-60 wt.% and especially at least approximately 35-50 wt.% the compound (I).

For the manufacture of medicaments which contain one or more compounds of the present invention, and/or for use of the medicines of the present invention usually use the Xia known methods of pharmaceutical technology. For this purpose, the active compounds are technological process with suitable pharmaceutically acceptable auxiliary substances and substances-carriers for the manufacture of dosage forms that are applicable for a variety of indications and areas of introduction. In this context, drugs can be produced in such a way that in each case achieved the desired rate of release, such as a rapid accumulation and/or the effect of a slow release or Deposit.

For a typical application to the skin or mucous membrane may be mentioned conventional emulsions, gels, ointments, creams systems mixed phase or amphiphilic emulsion systems (mixed phase oil/water-water/oil), as well as liposomes and transfersome or patches, preferably ointments and creams, especially preferably ointment. The active compound is preferably applied topically to the site on which there are changes and/or disease of the skin or mucous membrane.

In addition to the known methods of application on the skin and/or mucosa, the following preparations are suitable for use as a special pharmaceutical preparations that can be applied topically, locally or regionally: emulsions, creams, ointments, effervescent tablets or suppositories that you can enter genitale, Vaga is real or rectal, in particular genitale and vaginally. It is also possible to produce rectal capsules gelatin-based or other substances-carriers. Suitable bases for suppositories are solid fats, such as Witepsol®, Massa Estarium®, Novata®, coconut oil, pasta glycerin/gelatin, glycerol gels/Soaps and glycols.

Examples of suitable auxiliary substances and/or substances vehicles are sodium alginate as the gelling agent for the manufacture of a suitable framework or cellulose derivatives, such as guar or xanthan gum, inorganic gelling agents such as aluminum hydroxide or bentonites (called thixotropic geleobrazovanie), derivatives of polyacrylic acid such as Carbopol®, polyvinylpyrrolidone, microcrystalline cellulose and carboxymethylcellulose. Also suitable are amphiphilic low-molecular and high-molecular compounds and phospholipids. Gels may be present in the form of hydrogels, water-based, and in the form of a hydrophobic organoclay, for example on the basis of mixtures of low-molecular and high-molecular paraffin hydrocarbons and petroleum jelly. The hydrophilic organogel can be obtained, for example, on the basis of high molecular weight glycols. These gel-like forms are washing the Xia. However, the preferred organosilane are the hydrophobic organogel. Particular preference is given to hydrophobic auxiliary substances and additives, such as vaseline, wax, alerby alcohol, propylene glycol monostearate and monopalmitate propylene glycol. Of course, you can add soothing the skin and/or inhibiting inflammation additives that are known in the art, such as obtained by synthetic compounds and/or extracts and/or active compounds from medicinal plants, in particular bisabolol and panthenol. In addition, you can also add dyes, for example, yellow and/or red iron oxide and/or titanium dioxide to match in color.

Emulsifiers which can be used are anionic, cationogenic or neutral surfactants, such as Soaps of alkali metals, Soaps, metals, Soaps, amines, from sulphonated compounds, invert Soaps, higher fatty alcohols, partial esters of fatty acids and sorbitan and polyoxyethylenesorbitan such as lanette, wool fat, lanolin, or other synthetic products to obtain emulsions of the type oil/water and/or water/oil.

You can use vaseline, natural or synthetic waxes, fatty acids, fatty alcohols, esters of fatty KIS is on, for example, monoglycerides, diglycerides or triglycerides, paraffin oil or vegetable oil, hydrogenated castor oil or coconut oil, pork fat, synthetic fats, for example on the basis of Caprylic acid, capric acid, lauric acid or stearic acid, such as Softisan®or mixtures of triglycerides such as Miglyol®can be used as lipids, in the form of fatty and/or oily and/or wax components for the manufacture of ointments, creams or emulsions.

You can use, for example, osmotically active acids and alkaline solutions, such as hydrochloric acid, citric acid, sodium hydroxide solution, potassium hydroxide solution, sodium hydrogen carbonate and, in addition, buffer systems, such as citrate, phosphate, Tris buffer or triethanolamine, to adjust pH. You can also add preservatives such as methylbenzoate, or propylbenzoate (parabens), or sorbic acid, to increase stability.

As an additional form, which can be applied topically, may be mentioned powders and pastes and mortars. As bases, determining the consistency of toothpaste often contain hydrophobic and hydrophilic excipients, preferably, however, a hydrophobic excipient, contains very Bo the greater the proportion of solids. With the purpose of improving the dispersibility and fluidity and slipperiness, and to prevent the formation of agglomerates, powders or powders for topical application may, for example, contain starch, such as wheat or rice starch, dispersed using a flame silicon dioxide or silica, which also serve as diluent.

Dosage forms that are suitable for each individual case can be made on the basis of farmaceutico-physical principles, in accordance with the guidelines and methods of preparing the compositions, known to specialists.

The drug of the present invention preferably contains about 35 wt.% isopropylmyristate, about 15 wt.%, at least one catechol, about to 24.5 wt.% vaseline, approximately 20 wt.% wax, about 5 wt.% of propylene glycol monostearate or monopalmitate propylene glycol and about 0.5 wt.% olejowego alcohol.

The drug of the present invention and/or pharmaceutical metabolites are used for the treatment of viral skin diseases and/or tumor diseases.

The term "pharmaceutical metabolite" should be understood as one or more compounds that arise during the application in the biological IU is abolism. These metabolites may represent an intermediate compound resulting from intermediate metabolism, or end products of metabolism. These metabolites preferably represent metabolic products resulting from application to the skin and/or mucous membranes, in particular the products of hydrolysis of compounds having the formula (I). Possible products of hydrolysis can be obtained, for example, of the radicals a and/or radical Century

Under viral skin diseases understand skin diseases which are induced or caused by viruses and/or associated with viral infections. They contain, for example, such skin conditions like warts, genital warts, benign tumors of the skin and/or mucous membranes caused by papilloma viruses, such as plantar warts, common warts, flat plane warts, wart epidermodysplasia, genital warts, flat warts, bowenoid papules, papillomas of the larynx and oral mucosa, focal epithelial hyperplasia, herpetic fever, Kaposi's sarcoma, chickenpox and herpes zoster.

These viral skin diseases and/or tumor diseases are caused, at least one virus or viruses of the papilloma, frequent in the spine of the human papilloma virus, such as HPV 1, 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, at least one herpes virus or herpes viruses such as herpes simplex virus 1, herpes simplex virus 2, varicella zoster or herpes virus man, such as 1, 2, 3, 4, 7, or 8.

The following examples are intended to explain the present invention without its limitations. Experts can modify the present invention, accordingly, to the extent possible, without derogating from the protected volume.

Examples

A clinical trial to compare the ointments and creams containing isopropylmyristate

93 patients (in each case was divided equally on men and women) participated in a multicenter clinical trial, which was conducted only 30 different centers in Germany and Russia. The study was randomized and conducted double-blind method. In the trials studied the clinical efficacy of two different compositions of isopropylmyristate (ointments and creams) for the treatment of external genital warts.

Studied composition had the following composition:

Cream 1:
SubstanceNumber, wt.%
Cera alba6,996
2,798
Lameform TGI5,598
Cetiol V6,996
Isopropylmyristate13,992
Tocopherol0,699
Controx KSof 0.066
Glycerin6,996
Disodium EDTA0,001
Magnesium sulfate1,399
D-panthenol0,699
Purified water53,678
Red iron oxide*0,025
Yellow iron oxide*0,054
* Dyes were added to match the color.

Ointment 1:
SubstanceNumber, wt.%
White petrolatum, USP34,023
White wax, NF25,000
Isopropylmyristate, NF35,000
Alerby alcohol, NF0,500
The propylene glycol monostearate, NF5,000
Red iron oxide*0,022
Yellow iron oxide*0,055
Titanium dioxide, USP0,400
* Dyes were added to match the color.

Patients inflicted local test drug three times a day or as long until genital warts is not fully cured, or a maximum of twelve weeks.

During the test the following data were obtained:

Full recovery,%

Cream 1Ointment 1
Men39,142,1
Women35,033,3

Partial recovery in % (this corresponds to at least 75% recovery, based on the total area of the genital warts)

Cream 1Ointment 1
Men43,563,2
Women50,052,4

The results show that there is an unexpectedly high degree of full recovery or partial recovery compared with values placebo in similar studies using different compositions, in which spontaneous regression of genital warts is approximately 20% for women and priblizitel is but 5% of men (cream Aldara™ (Imiquimod)5% of the Product Monograph sold by 3M Pharmaceuticals, Northridge, CA, Beutner K.R. et al. (1998) J. Am. Acad. Dermatol. 38, 230-9, L. Edwards et al. (1998) Arch. Dermatol. 134 (1); 25-30).

This therapeutic effect is attributed to isopropylmyristate, whose antiviral effect was subsequently demonstrated for the first time.

A clinical trial to compare the ointments and creams containing isopropylmyristate and Polyphenon® E

272 patients (in each case was divided equally on men and women) participated in a multicenter clinical trial, which was conducted only 30 different centers in Germany and Russia. The study was randomized and conducted double-blind method. In the trials studied the clinical efficacy of two different compositions of isopropylmyristate and Polyphenon® E (ointments and creams), compared with the compositions of example 1, containing isopropylmyristate, for the treatment of external genital warts.

Studied composition containing Polyphenon® E, had the following composition:

Cetiol V
Cream 2:
SubstanceNumber, wt.%
Polyphenon® E10,000
Cera alba5,263
Monomuls2,105
Lameform TGI4,211
5,263
Isopropylmyristate10,526
Tocopherol0,526
Controx KS0,050
Glycerin5,263
Disodium EDTA0,001
Magnesium sulfate1,053
D-panthenol0,526
Purified water55,213

Ointment 2:
SubstanceNumber, wt.%
Polyphenon® E15,000
White petrolatum, USP24,500
White wax, NF20,000
Isopropylmyristate, NF35,000
Alerby alcohol, NF0,500
The propylene glycol monostearate, NF5,000

Patients inflicted local test drug three times a day or as long until genital warts is not fully cured, or a maximum of twelve weeks.

During the test the following data were obtained:

Full recovery, %
Cream 1 Ointment 1Ointment 2
Men39,153,942,161,0
Women35,039,533,356,8

Partial recovery (≥75%%)
Cream 1Cream 2Ointment 1Ointment 2
Men43,564,263,280,5
Women50,047,452,481,1

The analysis of tests shows that when comparing ointment 1 and cream 1, on the one hand, and ointments 2 and cream 2, on the other hand, the combination of isopropylmyristate and Polyphenon® E is an unexpected increase in efficiency of the medicine.

If the efficiency ointment 2 now compare with the efficacy of 2, it becomes obvious that ointment 2 is significantly more effective than the cream 2. This suggests a synergistic effect of Polyphenon® E and isopropylmyristate in hydrophobic ointment.

As a result of this synergistic effect, the individual active compounds in the composition to achieve the same effect can be used in much manchikanti, than the quantity of the corresponding individual components. Thus, the use of the above synergistic composition has advantages not only from the point of view of effect, but also from the standpoint of cost of manufacture of this composition, which, in turn, has a positive effect on the cost of treatment of the patient.

1. Drug for the treatment of warts, which contain as pharmaceutically active compounds a compound selected from isopropylmalate, isopropylmyristate, isopropylpalmitate, isopropylmalate, atelierista, propylpyridine, butylmalonate and/or ethyloleate, and at least a mixture containing 2-20 wt.%, preferably 4-15 wt.%, in particular 10-11 wt.% (-)-epicatechol, 2-20 wt.%, preferably 5-15 wt.%, in particular, 5-7 wt.% (-)-epicatechol, 1-25 wt.%, preferably 3-15 wt.%, in particular, 5-7 wt.% (-)-epigallocatechol, 40-75 wt.%, preferably 57-67 wt.%, in particular 61-66 wt.% (-)-epigallocatechingallate, 0.05 to 5 wt.%, preferably 0.1 to 1 wt.%, in particular 0.1 to 0.6 wt.% (+)-gallocatechin and/or 0.5-20 wt.%, preferably 1-10 wt.%, in particular 1-5% by weight (-)-allocationally, where the medicinal product contains 1-30 wt.%, preferably 2-20 wt.% and, in particular, 15-18 wt.% a mixture of catecholo and at least 5-90 wt.%, preferably at least 10-70 wt.%, in particular at m is re 25-60 wt.% and especially at least 35-50 wt.% connection selected from isopropylmalate, isopropylmyristate, isopropylpalmitate, isopropylmalate, atelierista, propylpyridine, butylmalonate and/or ethyloleate.

2. The drug according to claim 1, characterized in that the mixture contains about 10.8 wt.% (-)-epicatechol, 6.5 wt.% (-)-epicatechol, 9.2 wt.% (-)-epigallocatechol, of 54.8 wt.% (-)-epigallocatechingallate and/or 4.0 wt.% (-)-allocationally.

3. The drug according to claim 1 or 2, characterized in that category separated from the tea extract.

4. The drug according to claim 1 or 2, which also contains additives and/or auxiliary substances.

5. The drug according to claim 4, characterized in that additives and/or auxiliary substances are hydrophobic and preferably selected from petrolatum, wax, olejowego alcohol, propylene glycol monostearate and monopalmitate propylene glycol.

6. Drug for the treatment of warts, which contains 35 wt.% isopropylmyristate, 15 wt.%, at least one catechol and 24.5 wt.% vaseline, 20 wt.% wax, 5 wt.% of propylene glycol monostearate or monopalmitate of propylene glycol and 0.5 wt.% olejowego alcohol.

7. The drug according to claim 1 or 2, where the warts are genital warts.



 

Same patents:

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention provides novel urea-substituted imidazoquinoline ethers depicted by general formula I: (1), in which X represents -CHR5- or -CHR5-alkyl group; R1 is selected from radicals: -R4-NR8-CR3-NR5-Z-R6-Alk, -R4-NR8-CR3-NR5-Z-R6-Ph, -R4-NR8-CR3-NR5-Z-R6-furanyl, -R4-NR8-CR3-NR5R-7, phenyl being optionally substituted by one or more substituents selected from methyl, methoxy, methylthio, cyano, hydrogen, dimethylamino, and acetyl; R2 is selected from hydrogen, alkyl, and alkyl-Y-alkyl; R3 represents =O or =S; R4 represents alkyl optionally substituted by one or several O-groups; each of R5 represents C1-C10-alkyl; R6 represents ordinary bond or alkyl; R7 forms cycle together with R5; R4 represents hydrogen, C1-C10-alkyl, or forms morpholine ring together with R8; Y represents -O-; Z ordinary bond, -CO-, or -SO2-; n=0; each of R is independently selected from C1-C10-alkyl, C1-C10-alkoxy, hydroxy, halogen, and trifluoromethyl; or pharmaceutically acceptable salt of forgoing compounds. Described are further compounds of general formula II, intermediates of compounds of general formulae III and IV, pharmaceutical compositions based on compounds I and II, which are immunomodulators for synthesis of cytokines based on compounds I and II, methods of treating viral diseases utilizing compounds I and II, and methods of treating tumor diseases utilizing compounds I and II.

EFFECT: expanded synthetic possibilities in quinoline series and increased choice of therapeutically useful compounds.

25 cl, 4 tbl, 44 ex

FIELD: medicine, immunology.

SUBSTANCE: the present innovation deals with specific prophylaxis of smallpox and viral hepatitis B. The kit contains two tablets each contains stabilizing additives, a filler and lyophilized alive viral material worked out based upon recombinant VOV strain at typical VOV properties expressing proteins preS2-S and HBs virus of hepatitis B virus, the first immunizing dosage corresponds to minimal quantity of viral material being sufficient to obtain weak immune response in the body in case of insignificant at insignificant reactogenicity, and immunizing dosage of the second - maximal quantity of viral material that causes pronounced and prolong immune response in the body at no negative side action. The technique of applying the kit of bivaccine tablets, first, one should use the 1st tablet at minimal dosage of bivaccine, as for the 2nd tablet - with maximal dosage of bivaccine it should be taken till the moment of developing humoral answer (in 7-14 d) after injecting the 1st tablet at minimal immunizing dosage of bivaccine. The innovation enables to create stable immunity.

EFFECT: higher efficiency.

4 cl, 5 ex, 6 tbl

FIELD: veterinary science, virology, biotechnology.

SUBSTANCE: the suggested vaccine contains the suspension of avirulent and purified antigenic material out of the strain N 101 of cattle rotavirus (Research Institute of Animal Protection) obtained in mono-layer culture cells MDBK or SPEV at accumulation degree being 106 viral particles/ml, not less and activity in IEA being 5.0 log2, not less, and target additives: aluminum hydroxide and saponin in efficient ratios. The strain is deposited in collection of FGU VGNKI under registration number - a culture strain N 101 Research Institute of Animal Protection-DEP. The suggested vaccine is highly immunogenic, safe and areactogenic, it is capable to protect cattle stock against epizootic agent of rotaviral infection circulating in Russian territory.

EFFECT: higher efficiency.

14 cl, 9 ex, 10 tbl

FIELD: medicine, biology.

SUBSTANCE: the present innovation deals with the technology for manufacturing the series of preparations being of immunoregulating action and could be applied for manufacturing vaccines and preparations for the purposes mentioned. It is necessary to dissolve 3000 g sugar in bidistilled water up to saturated syrup to sterilize it due to boiling followed by cooling it up to about 45-50°C, then one should add as a basis 30 g protein bile fraction of two ad more even-toes animals dissolved in 200 g bidistilled water, the mixture should be thoroughly mixed to dry it up to the end in oven drier at 45-50°C, then the mixture should be ground to sterilize the powder obtained that contains a target product with quartz irradiation to be packed into gelatinous capsules NN 1-3 at 0.5-1.5 g dosage. The innovation provides the development of reliable, economically profitable technology for manufacturing native preparations of immunoregulating action that enables to shorten terms of therapy, prolong terms of remission, achieve complete recovery in case of viral diseases and intoxications and decrease lethality percentage in case of the diseases mentioned.

EFFECT: higher efficiency.

6 ex

FIELD: medicine, pharmacology, bioorganic chemistry, pharmacy.

SUBSTANCE: invention relates to the effective using amount of β-L-2'-deoxynucleoside of the formula (I) or (II) used in manufacturing a medicinal agent used in treatment of hepatitis B, pharmaceutical compositions containing thereof, and methods for treatment of hepatitis B. Proposed agent shows the enhanced effectiveness in treatment of hepatitis B.

EFFECT: enhanced and valuable medicinal properties of agent.

83 cl, 6 tbl, 11 ex

FIELD: medicine.

SUBSTANCE: method involves carrying out revaccination of children, not reaching the age of 6 years from May to September, next year within the period from May to September.

EFFECT: enhanced effectiveness of revaccination.

1 tbl

FIELD: medicinal plants, chemical technology.

SUBSTANCE: method involves extraction of milled licorice (Glycyrrhiza uralensis, Fischer) roots with 0.5% aqueous solution of NH4OH. The total triterpene acids of extract are precipitated with concentrated H2SO4 followed by extraction of total triterpene acids with 1% solution of H2SO4 in acetone, precipitation of glycyrrhizic acid triammonium salt with 25% solution of NH4OH and its conversion to monoammonium salt by re-crystallization from glacial CH3COOH and purification of the latter by re-crystallization from 85% ethanol. Invention provides enhanced yield of the end product.

EFFECT: improved preparing method, enhanced yield.

1 dwg, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of piperazine of the general formula: or their pharmaceutically acceptable salts wherein Ra - R8a mean phenyl; R8b means pyridyl, or R8 means naphthyl; R1 means hydrogen atom; R2 - R9, R10, R11 mean substituted phenyl; R9, R10, R11 mean substituted pyridyl or pyrimidyl; R9, R10, R11 mean substituted pyridyl-N-oxide or pyrimidyl-N-oxide; R12, R13 mean substituted oxazolyl, naphthyl, fluorenyl, compounds of formulae , or ; R3 means hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkyl-(C1-C6)-alkyl; R8 means phenyl; R8 means phenyl-(C1-C6)-alkyl, or R8 means thienyl-(C1-C6)-alkyl; R4, R5, R7 and R13 mean independently hydrogen atom or (C1-C6)-alkyl; R6 means hydrogen atom or (C1-C6)-alkyl; R8 means 1-3 substitutes that mean independently hydrogen atom, halogen atom, (C1-C6)-alkoxyl or -CF3; R8a means 1-3 substitutes that mean independently hydrogen atom, halogen atom, -CF3, -CF3O, -CN; R14 means phenyl, -NHCOCF3 and imidazolyl; R8b means 1-3 substitutes that mean independently hydrogen atom or halogen atom; R9 and R10 mean independently (C1-C6)-alkyl, halogen atom, -NR17R18, -OH, -CF3 and -OCH3; R11 means R9, hydrogen atom, phenyl, -NO2, -CN, -CH2F, -CHF2, -CHO, -CN=NOR17, pyridyl, pyridyl-N-oxide, pyrimidinyl, pyrazinyl, -N(R17)CONR18R19, -NHCONH-(chloro-(C1-C6)-alkyl), -NHCONH-((C3-C10)-cycloalkyl-(C1-C6)-alkyl), -NHCO-(C1-C6)-alkyl, -NHCOCF3, -NHSO2N-((C1-C6)-alkyl)2, -NHSO2-(C1-C6)-alkyl, -N(SO2CF3)2, -NHCO2-(C1-C6)-alkyl, (C3-C10)-cycloalkyl, -SR20, -OSO2-(C1-C6)-alkyl, -SO2CF3, hydroxy-(C1-C6)-alkyl, -CONR17R18, -CON(CH2CH2-O-CH3)2, -OCONH-(C1-C6)-alkyl, -Si(CH3)3 or -B(OC(CH3)2)2; R12 means (C1-C)-alkyl or R14-phenyl; R14 means 1-3 substitutes that mean independently hydrogen, (C1-C6)-alkyl, -CF3, -CO2R17, -CN, (C1-C6)-alkoxyl and halogen atom; R15 and R16 mean independently hydrogen atom and (C1-C6)-alkyl, or R15 and R16 mean in common (C2-C5)-alkylene group and in common with carbon atom to which they are bound form (C3-C6)-spiran ring; R17, R18 and R19 mean independently hydrogen atom or (C1-C6)-alkyl; R20 means (C1-C6)-alkyl. Also, invention describes pharmaceutical compositions containing these compounds and using novel compounds as CCR5 antagonists in treatment of HIV infection, arthritis, asthma, cerebrospinal sclerosis and other diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

29 cl, 30 tbl, 31 ex

FIELD: chemistry of proteins, virology, pharmacy.

SUBSTANCE: invention relates to novel physiologically active protein conjugates that can be used in medicine. Proposed conjugates is formed by a protein molecule and polyethylene glycol and corresponds to the formula: wherein protein represents interferon α-2b; n and n1 have values providing an average molecular mass of links from about 7500 Da to about 35000 Da. Conjugate shows the enhanced stability as compared with the known analogs. Also, invention relates to a pharmaceutical composition possessing an antiviral activity and containing the indicated conjugate, and to a method for control of viral infection.

EFFECT: valuable medicinal and biological properties of conjugates.

4 cl, 1 dwg, 6 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of pyrazine of the general formula (I): and their salts wherein R1 represents hydrogen atom or halogen atom; R2 represents hydrogen atom or protected or unprotected group of monophosphoric, diphosphoric or triphosphoric acid; R3, R4, R5 and R6 can be similar or different and represent hydrogen atom, halogen atom, substituted or unsubstituted, protected or unprotected hydroxyl group or amino-group; or R4 and R6 taken in common form a simple bond; A represents oxygen atom or methylene group; n = 0 or 1; Y represents oxygen atom pr NH-group. Compounds elicit the excellent antiviral activity and useful as a therapeutic agent in treatment of viral infections. Also, invention describes a pharmaceutical composition based on compounds of the formula (I) and derivatives of fluoropyrazine carboxamide as intermediate compounds used in synthesis of compounds of the formula (I).

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

13 cl, 6 tbl, 57 ex

FIELD: medicine, combustiology.

SUBSTANCE: invention relates to a method involving the complex antibacterial treatment of burn generalized infection using topical and parenteral effect with antiseptics and antibiotic in patients suffering from deep surface burns. Solution "Butol" is applied on wound at 1-3 days as water-drying dressing. For the following 4-10 days in each other day ointment "Butolol" is applied on wound and ointment "Butolan" is applied in the following period in surface burns up to complete epithelization and in deep burns after surgery - necrectomy and in preparing wounds for autodermoplastic. Ceftriaxone is administrated in the dose 2 g per a day simultaneously with the topical treatment from 1-st to 12-th day and galavite is administrated by intramuscular route in the dose 200 mg in the first day and in the dose 100 mg from the 2-d to 12-th day per 24 h. Method provides enhancing effectiveness of treatment of burn generalized infection and to reduce hospitalization period of patients.

EFFECT: improved method of treatment.

2 ex

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention provides novel N6-substituted adenine-based heterocyclic compounds depicted by general formula I: , for which meanings of radicals are presented in description, and pharmaceutically acceptable salts thereof manifesting anticancer, mitotic, immunosuppressive, and antiaging activities for vegetable, animal, and human cells, and methods for preparation thereof. Included are also pharmaceutical compositions, cosmetic preparations, and growth regulators, which contain indicated derivatives as active components. Application of indicated derivatives for preparing therapeutical preparations, and cosmetic preparations are also described.

EFFECT: expanded synthetic possibilities in adenine series and increased choice of various biologically active agents.

10 cl, 10 dwg, 9 tbl, 14 ex

FIELD: medicine; dermatology.

SUBSTANCE: photo-chemotherapy course is taken four times a week during four weeks. Prolactin and thryrotrophic hormone is found in blood. Parlodel is prescribed at specific factors in parallel with photo-chemotherapy. In case factors of prolactin grow higher than 720 mME/l and thryrotrophic hormone gets higher than 4,2 mcME/ml, parlodel is introduced before meals in amount of 1,25 mg twice a day in mornings and evenings during 30 days. Then it is introduced during 2 months in amount of 0,625 mg mornings and evenings. Then parlodel is introduced during 3 months in amount of 0,625 mg twice a day in the evening and in the morning. In 6 months levels of prolactin and thryrotrophic hormone are checked again. If prolactin factors excess 65-720 mME/l and thryrotrophic hormone factors excess 0,4-4,2 mcME/l, introduction of prolactin is canceled. If prolactin factor is higher than 720 mME/l and thryrotrophic hormone factor is higher than 4,2 mcME/l, course is repeated.

EFFECT: improved efficiency of treatment; prolonged remission periods; reduced side effects.

3 att

FIELD: organic chemistry, vitamins.

SUBSTANCE: invention relates to novel triaromatic compounds, namely, analogs of vitamin D of the general formula (I): wherein values R1, R2, R3, X and Y are given in claim 1 of the invention claim. Also, invention relates to using these compounds in pharmaceutical compositions designated for treatment of the following diseases: (1) dermatological diseases associated with differentiation disturbance or proliferation of keratinocytes or sebocytes; (2) keratinization disorders; (3) dermatological diseases associated with disturbance of keratinization with inflammatory and/or immunoallergic components; (4) inflammatory diseases that don't represent keratinization disturbance; (5) cutaneous or epidermic expansion; (6) dermatological disorders, for example, vesicle dermatosis and collagenosis; (7) photoinduced or senile skin ageing, or for decreasing photoinduced pigmentations and keratosis, or any other pathologies associated with senile or photoinduced ageing; (8) skin healing and scar disturbances; (9) lipid function disturbances, such as acne hypersteatosis, simple seborrhea or seborrheic eczema; (10) dermatological diseases with immunologic component. Also, invention relates to cosmetic using the cosmetic composition for body and hair hygiene.

EFFECT: valuable medicinal and cosmetic properties of compounds.

16 cl, 3 tbl, 7 dwg, 10 ex

FIELD: chemical-pharmaceutical industry, medicine.

SUBSTANCE: invention relates to a pharmaceutical preparation comprising a lipophilic phase in the amount 1-10% by mass, mixture of a surface-active substance and an accessory surface-active substance wherein a surface-active substance is chosen from polyoxyethylene glycerol esters and fatty acids and polyoxyethylene sorbitan esters and fatty acids, and an accessory surface-active substance is chosen from poloxamers, block-copolymers of polyoxyethylene and polyoxypropylene in the amount 1-50% by mass, hydrophilic phase in the amount 40-80% by mass, and ciclosporin or its derivatives as an active component in the concentration 0.1-20% by mass. Proposed pharmaceutical preparation is made in colloidal formulation for topical using and designated for treatment and prophylaxis of skin pathological alterations, and/or skin adventitious, and/or mucous envelopes including mucous envelopes in digestive tract, urogenital ways and bronchial system, and/or conjunctives.

EFFECT: valuable medicinal properties of pharmaceutical preparation.

17 cl, 5 tbl, 11 dwg

FIELD: chemical-pharmaceutical industry, medicine.

SUBSTANCE: invention relates to a pharmaceutical preparation comprising a lipophilic phase in the amount 1-10% by mass, mixture of a surface-active substance and an accessory surface-active substance wherein a surface-active substance is chosen from polyoxyethylene glycerol esters and fatty acids and polyoxyethylene sorbitan esters and fatty acids, and an accessory surface-active substance is chosen from poloxamers, block-copolymers of polyoxyethylene and polyoxypropylene in the amount 1-50% by mass, hydrophilic phase in the amount 40-80% by mass, and ciclosporin or its derivatives as an active component in the concentration 0.1-20% by mass. Proposed pharmaceutical preparation is made in colloidal formulation for topical using and designated for treatment and prophylaxis of skin pathological alterations, and/or skin adventitious, and/or mucous envelopes including mucous envelopes in digestive tract, urogenital ways and bronchial system, and/or conjunctives.

EFFECT: valuable medicinal properties of pharmaceutical preparation.

17 cl, 5 tbl, 11 dwg

FIELD: medicine.

SUBSTANCE: method involves administering autolymphocyte fraction with stem cells and applying it to ulcer surface as injections. Then, newly separated fraction is applied as injection or application on ulcer surface with 7-8 days long pauses. The injections are done beginning from points arranged along ulcer perimeter and then over its surface in chessboard order. When administering the fraction as application, it is spread allover the ulcer surface.

EFFECT: enhanced effectiveness of treatment; excluded fraction and stem cells rejection.

2 cl

FIELD: medicine, pharmacy, biotechnology.

SUBSTANCE: invention relates to a novel biologically active substance comprising a complex of humoral factors of allogenic diploid fibroblasts. This substance is prepared by mechanical homogenization of donor tissue with addition of nutrient medium, culturing in wet atmosphere with 5% of CO2 and separation of supernatant fraction. Invention provides decreasing limitations in using and decreasing cost in preparing the proposed substance. Invention can be used in preparing medicinal agents possessing anti-inflammatory, immunomodulating and wound-healing properties.

EFFECT: valuable medicinal properties of substance, improved preparing method.

2 tbl, 10 dwg, 4 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of alkylurea of the formula (I): or its pharmaceutically acceptable salt, solvate or hydrate possessing properties of retinoid agonists (RAR), pharmaceutical compositions and medicinal agent. In compound of the formula (I): n means a whole number from 0 to 2; X means oxygen atom (O); Y means -OR5 wherein R5 means hydrogen atom; R1 means (C2-C8)-alkyl; R2 means hydrogen atom, alkyl, hydroxy- or oxo-group; R9 means hydrogen atom.

EFFECT: valuable medicinal properties of compound and pharmaceutical composition.

12 cl, 3 sch, 10 tbl, 20 ex

FIELD: medicinal plants, chemical technology.

SUBSTANCE: method involves extraction of milled licorice (Glycyrrhiza uralensis, Fischer) roots with 0.5% aqueous solution of NH4OH. The total triterpene acids of extract are precipitated with concentrated H2SO4 followed by extraction of total triterpene acids with 1% solution of H2SO4 in acetone, precipitation of glycyrrhizic acid triammonium salt with 25% solution of NH4OH and its conversion to monoammonium salt by re-crystallization from glacial CH3COOH and purification of the latter by re-crystallization from 85% ethanol. Invention provides enhanced yield of the end product.

EFFECT: improved preparing method, enhanced yield.

1 dwg, 1 ex

FIELD: method and composition for oral cavity care.

SUBSTANCE: claimed form contains a) 1-40 % of retaining agent, Selected from group containing water soluble hydrophilic resins, water soluble hydrophilic polymers or mixtures thereof, wherein retaining agent is capable of hydration under water or saliva action to produce retention coefficient of 1-4; and b) 60-90 % of local carrier. Moreover composition contains 65 wt.% of water-insoluble particles. Further disclosed is dental paste composition containing a) 30-65 % of water-insoluble particles as retaining agent, wherein solubility of retaining agent in water is less then 1 g/30 g at 25°C; b) 0.01-40 % of active agent for oral cavity care; c) 0.1-25 % of buffer agent. Claimed composition has retention coefficient of 1-4.

EFFECT: improved compositions for oral cavity care.

9 cl, 3 dwg, 5 ex

Up!