SK286288B6 - Dermatological topical preparations and method for their preparation - Google Patents

Abstract

Dermatological topical preparations contain as active substance at least one substance from the group of bifonazole, zincpyrithione, piroctone olamine, sulfoconcentrol, or a mixture of some of the said active substances, allantoin dexpanthenol and ingredients. Method for the preparation, in which viscous topical liquid with anti-fungicidal effect is prepared, intended for the treatment of skin fungal infections caused by moulds and yeasts.

Description

Technical field

The present invention relates to the field of the manufacture of dermatological topical preparations based on the use of antifungal agents which are characterized by fungistatic to fungicidal activity against dermatophytes, yeasts and molds.

BACKGROUND OF THE INVENTION

The topical formulations to be applied to the hair that cover the scalp include various shampoos, lotions, hair lotions and other types of products which are subsequently washed with water after application. They form foam with water when applied. They may have an emulsion, suspension, solution structure, may contain one or more active agents in a suitable vehicle, and other excipients such as surfactants, antimicrobials, stabilizers, viscosity regulators, antioxidants, and the like.

Shampoos contain three types of ingredients: primary surfactants, secondary surfactants, active and adjuvants. The primary surfactant group is responsible for detergent and hair cleansing, the secondary surfactants promote detergency. Substances of the third group are added for special effects and include antimicrobial anti-dandruff, soothing and balancing scalp, etc.

Alkyl sulfates and alkyl ether sulfates are used as basic surfactants, (Milan Chalabala et al .: Drug Technology, 1997).

A secondary surfactant group is added to improve detergency, increase foam stability, increase solubilization of fragrance and hydrophobic substances. The use of secondary anionic and non-ionic surfactants in shampoos aids the detergent of the primary surfactants, but when stored they tend to hydrolyse and, after use, the hair becomes rough and easily receives static charge.

Currently, azole derivatives are used in the treatment of superficial mycoses in accordance with WHO recommendations. Bifonazole has a similar chemical structure to clotrimazole, econazole, miconazole or climbazole, but differs from them in that it does not contain halogen and is therefore suitable for the skin. Fungicidal activity has been demonstrated in many clinical studies in the treatment of dermatomycoses, cutaneous candidiasis, seborrheic dermatitis (Segal R., David M., Ingber A., Lurie R., Sandbank M.,: Treatment with bifonazole shampoo for seborrhea and seborrheic dermatitis, 1992 , Soyinka F.: Bifonazole in the treatment of fungal skin infections in the tropics: a clinical and mycological study, 1987).

Fungistatic activity has been demonstrated with substances used against lupine formation. Sulfoconcentrol, salicylic acid in combination with hexachlorophene, selenium disulfide, zincpyrithione, piroctone olamine (Schrader K. H., Wirkung und Nebenwirkung modemer Antischuppenpraparate, 1982).

Recently there have been significant changes in the composition of shampoos. They move on to more sophisticated products that wash their hair, giving them a natural look, shine, elasticity, touch. Great emphasis is placed on the gentle effect on the scalp and eyes (patents of cosmetic companies Unilever, Gillette, Colgate-Palmolive).

Trends in dermatology are leading to improved functionality of shampoos with anti-dandruff and anti-fungal treatment. Resistance and dermatophyte susceptibility must not be reduced during use.

SUMMARY OF THE INVENTION

The invention provides a composition and a process for the preparation of dermatological topical preparations - shampoos which contain as active substances substances with fungistatic to fungicidal activity against dermatophytes, yeasts and molds.

The dermatological preparations according to the invention are topical systems of a certain viscosity intended to be applied to the skin (scalp with hair) with local action. These are solutions which contain as active antifungal agents azole derivatives or azole derivatives in combination with piroctone olamine, sulfoconcetrol, zinc pyritione in a suitable vehicle and other excipients such as primary and secondary surfactants, viscosity regulators, emollients, protective agents, moisturizers and allantoin-dexpantenol (alpanth).

Alkyl ether sulfate was used as the primary surfactant. Compared to alkyl sulfates, it has a more stable color, better solubility, and is a good solvent for nonpolar compounds that may be present in the formulation.

As a secondary amphoteric surfactant, a betaine derivative was used as a vehicle for dermatological non-irritating shampoos. Betaine derivatives form anionic and cationic surfactants depending on the pH of the system. These active substances have an antistatic effect, have a gentle effect on the skin, are compatible with electrolytes, detergents and germicides, and are nontoxic.

By the interaction of the antifungal agent and the adjuvants used in the dermatological shampoo of the present invention, soothing, moisturizing and restoring skin balance are achieved. A balanced combination of the active ingredient / excipient ratio of the present invention maintains the actual acidity of the pH-5.0 formulation, increasing the resistance of the hair to damage, giving it shine, and drying hair more quickly while remaining manageable. Importantly, the selected excipients do not irritate the eyes and scalp at the dose used.

The process according to the invention consists in treating the antifungal agent with the carrier 10-propylene glycol, adding lactic acid emolient to maintain the pH in the range of 4.0 to 6.0, as this increases the resistance of the hair to damage and lower pH shampoos are less irritating. Subsequently, primary and secondary surfactants, viscosity modifiers and hydration modifiers are added - emollients.

Using allantoin-dexpantenol (alpanthy), i. j. Panthenol, encapsulated on the allantoin core, achieves combined protection and healing properties - epithelization associated with skin nutrition. The interaction of both substances is more effective than the separate effect of each substance separately.

The composition of the invention has been clinically tested and has significant antimicrobial and antifungal effects. The antimicrobial effect was tested according to Ph.Eur. with strains used:

Pseudomonas aeruginosa NTCC

Staphylococcus aureus ATCC

Candida albicans ATCC

Aspergilus niger ATCC.

The criterion for evaluating the antimicrobial effect was expressed by the logarithm of the reduction in the number of microorganisms compared to the initial value of the inoculum.

The results in all cases met the prescribed reduction.

tribe Staphylococ cus aureus CFU / ml Pseudomonas aeruginosa CFU / ml Candida albicans CFU / ml Aspergillus niger CFU / ml horses, after inoculation 10.0 x 10 ⁵ 3.0 x 10 ⁵ 3.7 x 10 ⁴ 4.4 x 10 ⁴ Day 2 neg. neg. neg. neg. Day 7 neg. neg. neg. neg. Day 14 neg. neg. neg. neg. Day 28 neg. neg. neg. neg.

Assessment according to admissibility criteria for topical drugs as given in SL - 1 tab. 5.1.3.-2. The topical preparation has a slight effect on the basis of the test results obtained.

The efficacy of topical formulations containing an antifungal agent in the treatment of superficial skin infections such as epidermophytia corporis, epidermophytia manuum, epidermophytia peduum, epidermophytia interdigitalis, cutaneous candidiasis, pityriasis versicolor and erythrazma have been confirmed in many multicenter controlled studies. In comparative clinical studies, 1% once daily bifonazole has been shown to be as effective as other topical imidazoles such as clotrimazole, eco35 nazole, miconazole and sulconazole, administered twice daily and as oxiconazole or naphthidine administered once daily.

Clinical studies suggest that bifonazole is promising in the treatment of dermatides in children.

(Deichmann B.: Bifonazole versus Miconazol., 1985, Berg D., Regel E., Harenberg H. E., Plempel M .: Bifonazole and Clotrimazole. 1984)

The invention is further illustrated by the following examples without being limited thereto.

DETAILED DESCRIPTION OF THE INVENTION Example 1 Active substance: Bifonazolum 0.5 % wt. Vehicle composition: Lauromacrogol sodium sulfate 15 % wt. cocamidopropyl 7 % wt. Laureth - 4 1 % wt. Auxiliary raw materials: propylene 1 % wt. Lactic acid 0.8 % wt. Allantoin-dexpanthenol (alpantha) 0.8 % wt. Color PERFUME 0.2 % wt. Purified water ad 100.0 % wt. Example 2 Active substance: Bifonazolum 2.5 % wt. Vehicle composition: Lauromacrogol sodium sulfate 20 % wt. cocamidopropyl 10 % wt. Laureth - 4 2.5 % wt. Auxiliary raw materials: propylene 2 % wt. Lactic acid 3 % wt. Allantoin-dexpanthenol (alpantha) 2.5 % wt. Color perfume 0.2 % wt. Purified water ad 100.0 % wt. Example 3 Active substance: Bifonazolum 4.5 % wt. Vehicle composition: Lauromacrogol sodium sulfate 28 % wt. cocamidopropyl 10 % wt. Laureth - 4 4.5 % wt. Auxiliary raw materials: propylene 4 % wt. Lactic acid 4.9 % wt. Allantoin-dexpanthenol (alpantha) 4 % wt. Color Dalits 0.2 % wt. Purified water ad 100.0 % wt. Example 1,2,3 - preparation method

In an anchor mixer, propylene glycol is mixed with the active substance and lactic acid. The primary surfactant is gradually added and mixed until the active ingredient is completely dissolved. All the other ingredients of the prescribed composition, an aqueous solution of far10 by and allantoin-dexpanthenol (alpanthy), are added with continuous mixing. Finally, substances responsible for the viscosity of the formulation are added. The whole technological process takes place under continuous operation of the mixer. The temperature during the technological process must not exceed 30 ° C. The total time of the technological process is 2 hours.

Example 4

Active substance:

Piroctone olamine 0.5

The composition of the vehicle is the same as in Example 1

The auxiliary raw materials are the same as in Example 1 wt.

Example 5

Active substance:

Piroctone olamine The composition of the vehicle is as in Example 2

2.5 equal wt.

The auxiliary raw materials are the same as in Example 2

Example 6

Active substance:

Piroctone olamine 4.5

The composition of the vehicle is the same as in Example 3 wt.

The auxiliary raw materials are the same as in Example 3

Example 4,5,6 - preparation method

The preparation procedure is the same as in Example 1.

Example 7

Active substance:

Piroctone olamine

Sulfokoncentrol

The composition of the vehicle is the same as in Example 1

0.5

0.5 wt.

% wt.

The auxiliary raw materials as in Example 1 are the same

Example 8

Active substance:

Piroctone olamine

Sulfokoncentrol

The composition of the vehicle is the same as in Example 2

The auxiliary raw materials are the same as in Example 2

2.5

2.5 wt. % wt.

Example 9

Active substance:

Piroctone olamine 4.5

Sulfoconcentrol 4.5

The composition of the vehicle is the same as in Example 3 wt.

% wt.

The auxiliary raw materials are the same as in Example 3

Example 7,8,9 - preparation method

The preparation procedure is the same as in Example 1.

Example 10

Active substance:

Piroctone olamine

Bifonazolum

The composition of the vehicle is the same as in Example 1

The auxiliary raw materials are the same as in Example 1

Example 11

Active substance:

Piroctone olamine

Bifonazolum

The composition of the vehicle is the same as in Example 2

The auxiliary raw materials are the same as in Example 2

Example 12

Active substance:

Piroctone olamine

Bifonazolum

The composition of the vehicle is the same as in Example 3

The auxiliary raw materials are the same as in Example 3

0.5

0.5

2.5

2.5

4.5

4.5 wt.

% wt.

% wt.

% wt.

% wt.

% wt.

Example 10, 11, 12 - method of preparation

The preparation procedure is the same as in Example 1.

Example 13

Active substance:

Zinkpyrition

Bifonazolum

The composition of the vehicle is the same as in Example 1

The auxiliary raw materials are the same as in Example 1

0.5

0.5 wt.

% wt.

Example 14

Active Substance: Zinc pyritione Bifonazole

2.5

2.5 wt. % wt.

The composition of the vehicle is the same as in Example 2

The auxiliary raw materials are the same as in Example 2

Example 15

Active substance:

Zinc pyrition 4.5

Bifonazole 4.5

The composition of the vehicle is the same as in Example 3 wt. % wt.

The auxiliary raw materials are the same as in Example 3

Example 13,14,15 - Preparation Method

The preparation procedure is the same as in Example 1.

Example 16

Active substance:

Zinc pyrition 0,5

The composition of the vehicle is the same as in Example 1

The auxiliary raw materials are the same as in Example 1

Example 17

Active substance:

Zinc pyrition 2.5

The composition of the vehicle is the same as in Example 2

The auxiliary raw materials are the same as in Example 2

Example 18

Active substance:

Zinc pyrition 4.5

The composition of the vehicle is the same as in Example 3

The auxiliary raw materials are the same as in Example 3 wt.

% wt.

% wt.

Example 16, 17, 18 - Preparation The preparation procedure is the same as in Example 1.

Industrial usability

The invention is useful in the pharmaceutical industry in the manufacture of dermatological topical preparations intended for application to hair covering the scalp and the treatment of fungal infections.

Claims (3)

Dermatological topical preparations comprising an active substance selected from the group consisting of bifonazole, piroctone olamine, sulfoconcentrol, zinc pyritione, in an amount of 0.1 to SK 286288 Β6 5.0% by weight or a mixture of these active ingredients in an amount of 0.1 to 5.0% by weight. for each active ingredient represented, emollients comprising allantoin-dexpantenol which is a combination of panthenol encapsulated on the allantoin core in an amount of 0.1 to 5.0% by weight, lactic acid in an amount of 0.1 to 5.0% by weight, solubilizing agent propylene glycol in an amount of 0.1 to 5.0 wt.%, a primary surfactant of sodium lauromacrogol in an amount of 10.0 to 30.0 wt.%, in combination with an amphoteric surfactant, cocamidopropyl betaine in an amount of 6.0 to 13 wt. % 0 wt. and a laureth-3 viscosity regulator in an amount of 0.5 to 5.0 wt%. Method for the preparation of dermatological topical preparations according to claim 1, characterized in that a solution of the active substance or a mixture of active substances with a solubilizing agent is prepared, treated 10, then the primary surfactant, amphoteric surfactant, emollients, perfume, aqueous paint solution and allantoin-dexpanthenol, viscosity regulator, are added, and the temperature during the process must not exceed 30 ° C. A process for the preparation of dermatological topical formulations according to claim 2, characterized in that the acidity of the active substance solution and the solubilizing agent is adjusted by the addition of lactic acid. 15 to pH 4.0 to 6.0.