External agent for prophylaxis of skin infectious disease and method for prophylaxis

FIELD: medicine, dermatology, pharmacy.

SUBSTANCE: invention proposes a cosmetic agent for prophylaxis of skin infectious diseases that comprises an active substance and a conducting agent - multilamellar liposomes additionally. As an active substance dioxydin is used in the amount 0.00001-0.02 wt.-% to the external agent mass. Method for prophylaxis of skin infectious diseases involves using a cosmetic agent in the form of spoon or shampoo, or gel, or cream in the dose depending on selection of the composition and properties of cosmetic agent. Applying the agent results to reducing injurious effect on skin normal microflora, reducing danger from penetration of preparation in blood and providing high protection of skin against all species of infection. Invention can be used for prophylaxis of skin diseases in humans.

EFFECT: valuable medicinal properties of agent.

2 cl, 2 ex

The invention can be used for prevention of infectious diseases of human skin.

For the assessment of novelty and inventive step of the first of the independent objects of the claimed solution consider a number of known technical devices of similar purpose.

The known method of combating infections using antimicrobial composition containing the active substance, a binder, a solvent and water, in which the active substances used sangviritrin, the binder is polyvinyl alcohol, solvent - ethanol, see RF patent №2014085, a 61 K 35/78.

A known way of dealing with infections with the use of antibacterial agents, which used 1-cyclopropyl-6-nitro-7-(4-methylpiperazine)-4 oxo 1,4-dihydroquinoline-3 carboxylic acid or its hydrochloride, see RF patent №2024258, a 61 K 31/47.

There is a method of treatment of viral infections of the skin and mucous membranes, including local drug genetic engineering α₂-interferon, characterized by the fact that from the first days of the disease on the affected skin and/or mucous membranes simultaneously applied drug that has a local vasoconstrictive effect in combination with 2,5-5,0×10⁵IU/ml of genetic engineering α₂interferon-and 2,5-5,0×10⁴IU/ml gene and generoso γ -interferon 2-5 times a day for two days depending on the severity of the inflammatory phenomena, see RF patent №2022562 And 61 To 37/66.

There is a method of protecting human skin from infection, consisting in the use of external funds, which introduced different antibacterial drugs, as well as the beginning of the current used 10%emulsion of liposomes containing 0.1% alpha-tocopherol, see RF patent №2036637, a 61 K 7/00.

Known composition against acne with simultaneous treatment of superficial and deep layers of the skin, which is characterized by the fact that it includes a first dispersion of lipid vesicles capable of penetrating into the deeper layers of the skin and containing at least one active substance selected from antimicrobial agents, antiseptics, antibiotics, anti-inflammatories, protivoseborainey funds, retinol and its derivatives, for treating these deep layers, and a second dispersion of lipid vesicles capable of penetrating into the surface layers of the skin and containing at least one active substance selected from the keratolytic tools, protective agents, moisturizing agents and antioxidants for the treatment of these surface layers, see RF patent №2128506.

In this composition the lipid vesicles of the first dispersion is formed by at least one lipid in beremin of natural hydrogenated phospholipids, saturated synthetic phospholipids, paleolimnology ethers containing at least one linear fatty chain, paleolimnology esters containing at least one fatty chain, and mixtures thereof, and the lipid vesicles of the second dispersion is formed by lipids selected from natural ionic phospholipids containing unsaturated fatty chains having from 16 to 30 carbon atoms, paleolimnology ethers or polyelectronic esters containing one or more fatty chains in the molecule, including at least one fatty chain with a length of less than 16 carbon atoms, and mixtures thereof. The active substance contained in the first dispersion is selected from retinol and its derivatives, tretinoin and isotretinoin, octopirox, triclosan, geksamidina and its salts, chlorhexidine and its salts, azelaic acid and its salts, zinc salts and zinc oxide, clindamycin, N,N-dimethyl-N-2-(hydroxyethyl)-ammonium-5-n-dodecenylsuccinic, ketoconazole, hydrocortisone and its derivatives, acetylsalicylic acid; -glycyrrhetic acid. The active substance contained in the second dispersion is chosen from 5-n-octanoylthio acid, salicylic acid, antiscaling peroxide active agents nitroxide radicals, sun substances, -hydroxy acids, polyols.

Thus, this innovation is the invention relates to compositions against acne, comprising at least one active substance which is transferred to at least two different types of lipid vesicles. The composition is in the form of ointment, which is applied to the skin.

By the greatest number of similar features and achieved when using the result of this technical solution is selected as the prototype of the first independent object of the claimed invention.

In the prototype in every form of bubbles was used several active substances, and these active substances have the same function and/or distribution in the skin, on the surface and in deep layers, and the same type of exposure; substance active on the surface, and agents with deep-action are, therefore, complementary.

The active substance with deep action, in particular, selected from retinol (vitamin a) and its derivatives, such as retinol acetate, propionate or palmitate; tretinoin and isotretinoin.

As an active non-steroidal anti-inflammatory substances that can be used in this invention, referred to aspirin (acetylsalicylic acid) oxicam and - glycyrrhetic acid.

As the active steroid anti-inflammatory drugs that can be used in this invention, mention the s hydrocortisone and its derivatives, such as hydrocortisone acetate, phosphate or butyl acetate.

Tools that operate on the surface, mostly selected from keratolytic substances, such as 5-n-actinomycetoma acid, a - hydroxy acids such as lactic acid, glycolic acid or tartaric acid or fruit; antioxidants, for example, nitroxide radicals, substances active against Schwalenberg perechisleniya, such as tocopherol and its derivatives, sequestered substances and glycosylceramide; protective substances, such as sunscreen substances, moisturizers such as polyols, such as glycerin.

Means active on the surface, and substances with pubocervical action can imagine from 0.02% to 10% of the total weight of the composition.

The disadvantages of the prototype, which does not allow us to achieve our goal, is that this invention has a very narrow scope, as it refers to the composition of acne, which, as you know, are a complication of seborrhea (disease of the sebaceous glands) and are not contagious. And in the formula and in the description of the patent it is only about the treatment of acne and other related acne symptoms of seborrhea. The quantitative indicator of active substances in the composition, which ranges from 0.02% to 10% of its weight, also proves curative, not preventive care is the practical purpose of the composition, since this indicator is above the minimum of the effective doses for all components of the ointment.

Our invention is intended, firstly, not for treatment, and for prevention (skin protection), and secondly, it is designed to prevent communicable (infectious) diseases of the skin such as impetigo, ectima, ostiofollikulit, folliculitis, furuncle, carbuncle and other

The essence of the first independent object of the invention is expressed in the following essential features sufficient to achieve the above technical result.

According to the invention an external agent for infectious skin diseases, including anti-infective drug, characterized by the fact that as anti-infective drug used dioxidine.

This is a set of essential features of the first independent object of the invention providing technical result in all cases to which the requested amount of legal protection.

The essence of the second independent object of the invention is expressed in the following essential features sufficient to achieve the above technical result.

According to the invention a method of preventing infectious diseases of the skin, allcauses in the use of the above external funds, characterized by the fact that dioxidine connect with a conductor, conducting it into the skin cells in the deeper layers of the skin, which choose multilamellar liposomes, while dioxidine used dosages in relation to the weight of external funds below the minimum operating from 0.00001% to 0.02%.

This is a set of essential features that provide technical result in all cases to which the requested amount of legal protection.

The claimed technical solution is new, as both claimed variants are characterized by the presence of new sets of signs that are missing for all we know the technical objects of similar purpose. In the prototype is for a large number of drugs from different groups, however, and it is no coincidence that mention the drug the dioksidin group finokalia not, which suggests that the use of this product for purposes specified by us and cannot be considered explicitly derived from the prior art.

Direct technical result that can be obtained by implementation of the selected sets of characteristics is that antimicrobial drug dioxidine in liposomal form and the minimum current, i.e. obviously not enough is for therapy, the dosage does not violate the microflora on the surface of the skin and the most effective in anaerobic conditions in the thickness of the skin layer.

Obtaining mentioned technical result provides the appearance of the two versions of the object of the invention in General, the number of new useful properties, namely the reduction of detrimental effects on the normal microflora of the skin, and reduce the risk from getting drugs in the blood and high efficiency protect the skin from all kinds of infections.

Specified allows you to recognize the claimed technical solution meets the criterion of "inventive step".

The method is implemented as follows.

In the outer means in the form of soap, shampoo, cream or gel is injected dioxidine in liposomal form and the minimum current dosage of from 0.0001 to 0.03 wt.%. Specific dosage specify depending on the choice of the composition and properties of concrete cosmetics.

The concept of “minimum active dose” is well established in medical practice and is officially defined as the lowest dose of a substance that causes a pharmacological response, below which it is not shown, see Great medical encyclopedia edited BV Petrovsky, ed. 3. - M.: Owls. encyclopedia, 1977, s.

In aerobic conditions the surface of the stratum corneum obtained external means Pris is tstuat long, and does not affect its surface microflora, and its remains are quickly washed off from the skin surface. The bulk of external funds due to the liposomal formulation penetrates deep into the epidermis, where anaerobic conditions bactericidal effect dioksidina increases 10-30 times, which leads to prolonged and the most effective effects on the microflora in the thickness of the layer of the skin and its appendages, protecting them from the risk of inflammatory process from the inside.

A short time being declared for external use on the skin surface does not allow microorganisms to develop resistance to antimicrobial drugs. A significant advantage of the claimed means is that antimicrobial drug use in minimally effective doses, which minimizes the risk of contact with blood of the patient.

The stated us useful tool uses the ability dioksidina to increase their activity in anaerobic conditions. These properties were partially known (Bolshakov L.V. Antibacterial activity dioksidina in terms of Aero-anaerobiosis, Zhur. Antibiotics and medical biotechnology, 1986, No. 10, s-764, and Ponomareva TR Sensitivity of clinical strains of bacteria to dioksidin in vitro under aerobic and anaerobic conditions, jour. Antibiotics and medical biotechnology, 1987, No. 3, s-202), however, the detailed mechanism of action for the us run of the drug was first described in article V. Barinov, A.V. Males, A.V. Babkin, V. Atamanchuk, R.A. Grashin, J.V. Lizunov, P.P. Makarov “the Impact of new antibacterial agents with liposomes on the bactericidal action and automically skin. That can be an alternative to triclosan?”, published after the claimed priority date of our application and the number of authors present its applicants (Journal of dermatology and cosmetology No. 1, 2002, p.12-16).

In this article emphasized and for the first time scientifically proved that the results of microbiological studies and clinical observations of the last decades testify about the negative impact on autosecretary skin healthy individuals perfumery-cosmetic products containing various antibacterial agents. Their negative effect is manifested in the suppression of both pathogenic and protective of the resident microflora, resulting in regular use to dysbiosis of the skin and the appearance of pustular diseases. Such negative properties of the pharmaceutical agents of different classes (antiseptics, antibiotics and sulfa drugs, and triclosan). About the last one should say especially because triclosan does not apply to any antibiotics or antiseptics, having a non-standard mechanism of action. The drug blocks the enzyme enoyl-ASR-reducase, membership is involved in the synthesis of lipids of the cell membrane of a wide range of bacteria and fungi. He does not show them stability, on the one hand, and have no negative impact on human and animal cells, on the other hand. With such properties, triclosan is widely used in the perfume and cosmetic industry and is currently the United States has used 700 products of wide consumption as a preventive measure. However, recent reports that triclosan not only can kill the beneficial bacteria, not suppressing pathogenic and can cause the growth of the latter, leading to dangerous diseases (meningitis, sepsis and so on), make us new ways to consider the use of a preventive measure different antibacterial Soaps and other cosmetic products.

The tool protects skin from the appearance pustular diseases, should ideally be selectively inhibit only bacteria, without harming beneficial and not preventing them from multiplying. Today this problem has no concrete solutions. To resolve this problem, it was necessary: first, an antibacterial drug, is injected into the skin in a minimally effective dose, harmless in aerobic conditions for surface microflora, and at the same time dramatically increases its minimum inhibitory concentration in anaerobic conditions, while in the depth of the epidermis; W is ryh, the corresponding conductor, quickly remove the drug from the surface of the skin and effectively implementing it in the cells of the spinous and basal layers of the epidermis. This drug was dioxidine, and a corresponding guide - multilamellar liposomes.

Dioxidine (2,3-bis-(oxymethyl)finokalia 1,4-di-N-oxide) relates to pharmaceutical antimicrobial agents of broad-spectrum, including acting on the strains of bacteria that are resistant to other chemotherapeutic drugs, including antibiotics. As well as triclosan, bacteria do not develop resistance to it. Liposomes are tiny bubbles, the shell of which is silipigni layer simulating the cell membrane. This feature allows them integrating itself into the cell membrane, it is easy to penetrate, dragging the contents inside the bubble. Multilamellar liposomes have several silipigni layers, between which may be placed the solution was injected substances. Upon entering the cell, such liposome retains its inner shell, which then gradually being destroyed by lysosomal enzymes, provide a prolonged admission to the cytoplasm of a cell contained in the bubbles of biologically active substances. Dioxidine under anaerobic conditions increases its antimicrobial activity 10-30 times, and the liposome is we, in turn, not only provide a rapid penetration into the cell, but also increase the intracellular efficacy of transported drugs in 20-80 times (Kobrin HD Liposome-drug transporters. Medicine. 1989, 234; Margolis LB, L.D. Bergelson Liposomes and their interaction with cells. - M.: Nauka, 1986: 240).

We offer a liposomal option dioksidina to introduce into the soap in microdoses, ensuring the absence of disinfectant effect of the drug on the surface of the skin, and have a pronounced antibacterial effect when being inside the cells of the epidermis. Experimentally investigated the comparative effects of different varieties of soap (including prototypes soap containing liposomal dioxidine) on the bactericidal properties of the skin, and superficial and deep as useful, and its harmful microflora. Definition (after exposure to soap) bactericidal properties of the skin allowed to study the status of the barrier properties of the skin and observing the change in growth superficial and deep autosecretary gave information about how to change the properties of the microbial population inhabiting it.

Thus, it is proved that the other external funds, which would reach such a result (selective suppression only breznitsa the different bacteria, no harm useful and not interfering with them breed), which is obtained by use of funds, none of the known prior art means. This result is unattainable, and when using the prototype.

We argue that the use of us dioksidina that its delivery in the deeper layers of the skin, and at a dosage below the minimum current dose, i.e. all the stated aggregate differences, allows the object of the invention to show such properties that are not described in any of the sources of information and unattainable when using these separately known characteristics.

The industrial applicability of the claimed technical solution is not in doubt, so it is in both variants can be implemented using well-known methods and tools. Examples of practical implementation of the selected solutions.

Example 1. The patient P. for 22 years. Suffered during the year total furunculosis. A common treatment for positive results did not yield every 3-4 months new boils. After applying 2 times a week, Soaps prepared in accordance with the claimed method, containing dioxidine in liposomal form and subtherapeutic dosage, new boils were observed during the year.

Example 2. During the year, the wire is moose study on 300 volunteers, which previously were divided into 2 groups. First, experienced, consisted of 152 people. It daily, and weekly polyvac in the bath used is a hard soap with liposomal dioksidin. The second is 148 persons, control, used regular soap.

The results of the study noted that among the persons of the first group during the test period soap no one got sick pustular skin diseases, whereas in the control group, the incidence during this period was 41%.

The invention stated in both variants, United by a single inventive concept, increase the effectiveness of antibiotics in reducing their harmful impact on the resident microflora of the skin.

1. Exterior cosmetic for prevention of infectious diseases of the skin containing the active substance, characterized in that it further comprises a conductor-multilamellar liposomes, and as active substances are used dioxidine in the amount of from 0.00001 to 0.02 wt.% to the weight of external funds.

2. Method of prevention of infectious diseases of the skin through the use of cosmetic products, characterized in that the daily use of the tool in the form of soap, or shampoo, or gel, or cream dosage depending on the choice from the tava and properties of cosmetics.