RU2485955C2 - Pharmaceutical composition containing fluconazole and/or ketoconazole and/or terbinafine, and liposomes for local administration - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely to a composition for local administration. The pharmaceutical composition for local administration characterised by the fact that it contains ketoconazole, or fluconazole, or terbinafine, as well as liposomes, an emulsifier, a preserving agent, demineralised water taken in certain proportions (versions).

EFFECT: composition provides fast cutaneous penetration of the active substances.

3 cl, 4 ex

Description

The present invention relates to medicine, namely to pharmaceutical compositions for topical application containing fluconazole and / or ketoconazole and / or terbinafine and liposomes.

Recently, liposomes are most often used as carriers for various biologically active substances, such as vitamins, antibiotics, fruit acids, and others, in medicine. The assortment of liposome drugs contains ointments, creams and gels for the treatment of various diseases.

Fluconazole (2- (2,4-difluorophenyl) -1,3-bis (1H-1,2,4-triazol-1-yl) -2-propanol is an antifungal drug of the chemical group - triazole derivatives. It is active against a number of yeast fungi, dermatophytes and causative agents of opportunistic and endemic mycoses, used for various fungal infections: for cryptococcosis, including cryptococcal meningitis; for systemic candidiasis, candidiasis of the mucous membranes, vaginal candidiasis; for the prevention of fungal infections in patients with malignant neoplasms in the treatment of their cytostatics and and radiotherapy, in patients with AIDS, organ transplantation and in other cases, when depressed immunity, and there is a risk of fungal infection. Assign inside and intravenously. Medicines containing fluconazole for topical application, are not described.

Ketoconazole (1-cis-1-acetyl-4-para- [2- (2,4-dichlorophenyl) -2- (imidazol-1-yl-methyl) -1,3-dioxolan-4-yl] - methoxyphenyl- piperazine - an antifungal drug of the chemical group - imidazole derivatives. It is active against dermatophytes, yeast-like and mold fungi, pathogens of systemic mycoses, as well as leishmania. It is prescribed for superficial and systemic mycoses: dermatomycosis and onychomycosis caused by blastomycetes, mycosis of the hair; blastomycosis of the oral cavity and gastrointestinal tract, genitourinary organs, histoplasmosis and other mik ozas of internal organs, as well as with purulent leishmaniasis. Applied orally and topically. Described for local use: 2% shampoo in bottles of 25 and 60 ml; 2% cream in tubes of 15 g; 2% ointment in tubes of 20, 30, 40 and 50 g; vaginal suppositories 0.4 g each

Terbinafine (E) - N- (6,6-dimethyl-2-hepten-4-ynyl) -N-methyl-1-naphthylmethylamine is an antifungal drug of the chemical group - derivatives of N-methylnaphthalene. When applied topically (in the form of a cream or solution), it is slightly absorbed and has a slight systemic effect; diffuses rapidly through the skin and accumulates in the sebaceous glands; it is excreted with sebum, while relatively high concentrations are created in the hair follicles and hair. Within a few weeks after the start of treatment, it also penetrates the nail plates. Assign with onychomycosis, dermatomycosis, mycosis of the scalp, candidiasis of the skin and mucous membranes. Apply inside and out. Described for external use: 1% solution and spray in bottles of 15 and 30 ml; 1% cream in tubes of 10, 15 and 30 g.

The disadvantage of the above funds is that they penetrate poorly through the skin and, therefore, when applied topically, are effective only in its surface layers.

Essaven gel is known, which includes: escin, “essential” phospholipids and heparin sodium salt and is used for phlebitis, thrombophlebitis and hemorrhoids (Mashkovsky M.D. Medicines. - 15th ed., Revised., Rev. And add. - M.: New Wave, 2006 .-- p. 461-462).

Pharmaceutical compositions containing fluconazole and / or ketoconazole and / or terbinafine and liposomes are not described for topical application.

Thus, it is an object of the present invention to provide a topical pharmaceutical composition comprising fluconazole and / or ketoconazole and / or terbinafine and liposomes having rapid penetration through the skin.

According to the present invention, there is provided a topical pharmaceutical composition comprising fluconazole and / or ketoconazole and / or terbinafine and pharmaceutically acceptable carriers or excipients, characterized in that it further includes liposomes.

As a preferred embodiment of the claimed invention, a pharmaceutical composition is provided which has the following composition, wt.%:

fluconazole 0.01-5.0 liposomes 0.01-20.0 emulsifier 0.5-10.0 preservative 0.05-1.0 demineralized water 64.0-99.43

As another of the preferred embodiments of the claimed invention, a pharmaceutical composition is provided, which has the following composition, wt.%:

ketoconazole 0.01-5.0 liposomes 0.01-20.0 emulsifier 0.5-10.0 preservative 0.05-1.0 demineralized water 64.0-99.43

As another of the preferred embodiments of the claimed invention, a pharmaceutical composition is provided, which has the following composition, wt.%:

terbinafine 0.01-5.0 liposomes 0.01-20.0 emulsifier 0.5-10.0 preservative 0.05-1.0 demineralized water 64.0-99.43

The technical result of the present invention is to obtain a pharmaceutical composition based on fluconazole and / or ketoconazole and / or terbinafine and liposomes, which has the ability to quickly penetrate through the skin and, accordingly, rapid absorption. Ease of use and ease of dispensing are additional benefits.

The pharmaceutical composition of the present invention is usually prepared by conventional methods using solid or liquid pharmaceutically acceptable carriers or excipients selected from emulsifiers, dispersants, preservatives, flavorings, pH adjusters, polymer carriers and other excipients that are suitable for the preparation of compositions for topical use. The pharmaceutical composition of the present invention can be prepared in the form of a gel, cream, ointment and the like.

The rapid penetration through the skin is due to the binding of fluconazole and / or ketoconazole and / or terbinafine to liposomes containing hydrogenated lecithins in combination with cholesterol.

In preferred embodiments, the compositions are oriented: in the first case, for the treatment of candidiasis, in the second, for the treatment of dermatomycoses and onychomycoses, in the third, for dermatomycoses, the binding of active substances to liposomes ensures their stability and duration of action, as well as penetration into the deep layers of tissues affected by fungal flora .

The present invention is illustrated by the following examples.

EXAMPLE 1

The pharmaceutical composition in the form of a cream based on fluconazole and liposomes has the following composition:

fluconazole 5,0 carbomer 1,0 emulsifier 0.5 liposomes 2.00 preservative 0.2 demineralized water 91.30

The specified composition is prepared according to the following method. In demineralized water, when heated to 80 ° C, they mix: fluconazole, carbomer, emulsifier, then cool to 30 ° C and add liposomes and a preservative. The resulting cream is homogenized and vacuum.

EXAMPLE 2

The pharmaceutical composition in the form of a cream based on ketoconazole and liposomes has the following composition:

ketoconazole 5,0 carbomer 1,0 emulsifier 0.5 liposomes 2.00 preservative 0.2 demineralized water 91.30

The specified composition is prepared as in EXAMPLE 1, it differs in that ketoconazole is used instead of fluconazole.

EXAMPLE 3

The pharmaceutical composition in the form of a cream based on terbinafine and liposomes has the following composition:

terbinafine 5,0 carbomer 1,0 emulsifier 0.5 liposomes 2.00 preservative 0.2 demineralized water 91.30

The specified composition is prepared as in EXAMPLE 1, it differs in that terbinafine is used instead of fluconazole.

EXAMPLE 4

The study of the pharmaceutical composition with fluconazole and liposomes for the ability to quickly penetrate the skin.

To this end, the ability to rapidly penetrate into the skin of a composition of the present invention based on fluconazole and a control composition containing fluconazole without liposomes was compared. The tests were carried out on rabbits. These compositions were applied to the inner surface of the rabbit's ear. Absorption was determined by the amount of fluconazole remaining on the rabbit skin 10 minutes after application of the compositions, and expressed as a percentage of the initial amount of fluconazole in the composition.

Research results: control composition - 50% of the remaining fluconazole; the composition of the present invention is 10% of the remaining fluconazole. Similar results were obtained in the study of the compositions of examples 2 and 3.

Thus, the pharmaceutical composition according to this invention has the ability to quickly penetrate the skin, providing a more rapid manifestation of the therapeutic effect exerted by the active substances of the composition.

Claims (3)

1. A pharmaceutical composition for topical application, characterized in that it contains fluconazole, liposomes, emulsifier, preservative, demineralized water in the following ratio, wt.%:
fluconazole 0.01-5.0 liposomes 0.01-20.0 emulsifier 0.5-10.0 preservative 0.05-1.0 demineralized water 64.0-99.43 2. A pharmaceutical composition for topical application, characterized in that it contains ketoconazole, liposomes, emulsifier, preservative, demineralized water in the following ratio, wt.%:
ketoconazole 0.01-5.0 liposomes 0.01-20.0 emulsifier 0.5-10.0 preservative 0.05-1.0 demineralized water 64.0-99.43 3. A pharmaceutical composition for topical application, characterized in that it contains terbinafine, liposomes, emulsifier, preservative, demineralized water in the following ratio, wt.%:
terbinafine 0.01-5.0 liposomes 0.01-20.0 emulsifier 0.5-10.0 preservative 0.05-1.0 demineralized water 64.0-99.43