HU196306B - New dusting powders comprising bioactive material and process for preparing the same - Google Patents

Abstract

Dusting powder compositions contain cyclodextrin or a polymer thereof and optionally one or more cyclodextrin inclusion complex(es) as vehicle, diluent or excipient in an amount of 0.1 to 99.9 % and biologically active substance(s) and/or odorant(s) and/or colouring agent(s) in an amount of 99.9 to 0.1 %. The dusting powder compositions of the invention can therapeutically be used for disinfecting, as well as for mitigating skin inflammations and superficial pains.

Description

SUMMARY OF THE INVENTION The present invention relates to a process for the preparation of novel bioactive substance containing powders. The novel pumice powder compositions of the present invention contain cyclodextrin as a filler, diluent.

Coating powders are fine, highly adherent powders or powder mixtures applied to the skin that are used to protect, dry or cool the skin, or to achieve a therapeutic effect with certain pharmaceutical formulations. Such as disinfection, anti-inflammatory activity and, in some cases, promotion of percutaneous absorption of the active ingredient.

Swing powders need to have good water and fat-binding properties in order to provide excellent perspiration and fatty acids to the skin.

It is important that the pellet powder particles are not electrostatically charged or agglomerated due to shaking during storage or spraying, thus ensuring proper rheological properties of the pellet powder.

The raw materials for chewing powders are generally zinc stearate, zinc oxide, talc, calcium carbonate, bentonite, white matter, aluminum hydroxide, magnesium carbonate, colloidal silicon hydroxide and various starches. An excellent summary of the knowledge of carpet powders is provided by F. Gstirner, GrundstofTe und Vcrfahrcn der Arzneibcrcitung (Fcrdinand Enkc Verlag, Stuttgart, 1960, pp. 885-902).

The horsetail raw materials used to date are broadly divided into two groups, on the one hand various starches and, on the other, minerals such as wheatgrass. talc, kaolin, etc.

Commonly used in carp powder, but especially in cosmetics, starch has proved to be a particularly good medium for human skin fungi and, given its high prevalence of fungal infections, is considered to be almost a malfunction.

Coal powdered minerals of mineral origin are often heavily contaminated with bacteria such as Clostridium tetani, Clostridium perfringens, Bacillus anthracis (The Pharmaceutical Codex, XI. Edition, p. 315). Therefore, these materials must be heated at temperatures above 160 ° C for more than 1 hour before use, which makes them difficult to use.

In the past, fungal infections of the skin in humans have been mainly caused by Dermatophytons, but over the last decade, probably due to the spread of antibiotics, the proliferation of spongiform fungi has been observed. Currently, fungal infections are the main cause of dermatomycosis, in Hungary the fungal infections are mainly caused by Candida albicans, Trichophyton rubrum and Trichophyton mentagrophytes.

The aim of our experiments was to produce a new filler, diluent filler powder composition, which does not have the disadvantages of the used filler powder ingredients. Surprisingly, we have found that cyclodextrins (hereinafter referred to as "CDs") are suitable for use as a stock powder.

As is known, CDs are 6-, 7-, and / or. Macro rings composed of 8-glucopyranose units, named in the order of increasing number of glucose units: alpha-, beta- and / or glucose units. gamma-CD. They are made from starch, whereby the starch substrate is degraded by the cyclodextrin transglycosylase (CTG) enzyme and immediately enclosed in a ring. CDs can be used to make polymers, e.g. in the form of pearls, blocks or foams (Hungarian Patent Nos. 177,419 and 185,866, respectively).

Cyclodextrins can be considered as capsules of essentially molecular size. The molecular structure of the molecules is such that all of their hydroxyl groups are located on the outside of the molecule, but a weakly polar cavity of molecular size exists along the central axis of the molecule. This is the basis for inclusion complexing of cyclodextrins, also known as molecular encapsulation.

Cyclodextrins, their production, analytics, toxicological studies, and enormous numbers of industrial applications based on inclusion complexes have been the subject of extensive literature. (Szejtli, J., Cyclodextrins and their Inclusion Complexes, Academic Publisher, Budapest, 1982; and Szejtli, J. [ed.], Proceedings of the 1st International Symposium on Cyclodextrins, Academic Publisher, Budapest, 1982).

The use of cyclodextrins as filler and diluent for pumice powders not only is not obvious to the person skilled in the art, but, as previously known, appears to be contraindicated. It is obvious to those skilled in the art that crystallizable carbohydrates, i.e. non-polymeric carbohydrates, should not be used in talcum powder as they are a medium for human skin fungi and are hygroscopic and sticky, so the idea of using them in talcum powder is also rejected.

Nonetheless, we have found that cyclodextrins are not a suitable medium for skin infecting fungi. Thus, they can be used as diluents and fillers for powders.

To investigate how different fungal species utilize different carbon sources is

The following series of experiments were performed. Microorganisms tested: I. Sporadic Fungi (a) Candida albicans CBS 562 (b) Candida tropicalis CBS 433 (c) Candida guilliermondii 191 (d) Candida krusei K 47 (e) Candida pscudolropicalis 372 (f) Saccharomyces ccrevisiac OKI 1282 II. Yarn mushrooms (a) Trichophyton rubrum CBS 30338 (b) Trichophyton mentagrophytes CBS 50148 (c) Trichophyton (Keralomyces) ajelloi Who is he (d) Épidermophyton (loccosum OKI IV. (e) Microsporum persicolor OK! (f) Microsporum gypseum var. virosum CBS S00M

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Carbon sources studied: soluble starch (Amylum solubile), corn starch (Amylum maydis), glucose, maltose, beta-CD and beta-CD bead polymer.

Basic media used: Sabouraud medium,

szctétclc: peptone (Difco) 10g glucose 10g maltose 20g disodium hydrogen phosphate 10g potassium dihydrogenphosphate ι ε distilled water gives 1000 ml

In the above basic medium, substituting 10 g of glucose and 20 g of maltose as the carbon source with the aforementioned carbon sources, 18 varieties of media were obtained:

1. Sarbouraud (control).

2. Sarbouraud. without a carbon source.

3. Sarbouraud, 30 grams of glucose per carbon source.

4. Sarbouraud, carbon source 30 g maltose.

5. Sarbouraud, 30 g soluble starch as carbon source.

6. Sabouraud, 30 g corn starch as a carbon source.

7. Sabouraud, carbon source 10 g beta-CD g maltose.

8. Sabouraud, 20 g beta-CD g glucose as carbon source.

9. Sabouraud, 30 g beta CD as carbon source.

+ 20

10. Dist. water

11. Dist. water

12. Dist. water

13. Dist. water

14. Dist. water g glucose.

g maltose.

g soluble starch.

g corn starch.

g beta CD.

10 g of beta CD + 10 as carbon source

15. Sabouraud, pearl polymer + 20 g maltose.

16. Sabouraud, carbon source: 20 g beta-CD bead polymer + 10 g glucose.

17. Sabouraud, 30 g beta-CD bead polymer as carbon source.

18th Dist. water + 30 g beta-CD bead polymer.

Assay Design: 5-5 ml of media were inoculated with 5 * 10 'cells / ml of test organism and incubated at 27 ° C: sporadic fungi for 24 hours (1 and 2 days), filamentous fungi 72, 144 , 288 hours (3, 6, 12 days). The results are tabulated (Table I, Table II).

The data in the tables clearly show that the different test fungi grew differently on the nutrient medium variants. There were only two of the 8 media variations of the 5 carbon sources where none of the test fungi used increased; the dist. water + beta CD and dist. water + Beta-CD bead bead medium (Nos. 14 and 18).

Neither the β-CD nor the polymer of Sem served as a useful fungal base part, so among these substances alone, they appear to be suitable carriers or carriers for dermatological agents, the presence of which on the skin does not serve as a medium for various fungi.

Cyclodextrins and their inclusion complexes are non-hygroscopic and do not become sticky or flatten at relatively high relative humidity. They do not charge electrostatically, so they can be micronized well. Cyclodextrin inclusion complexes can be prepared by microcrystalline structures. All these properties make cyclodextrins and their inclusion complexes suitable for use as carrier powder in talcum powders.

CDs, when used in swaddling powders, may also have roles other than filler, carrier, related to inclusion complex formation. It is well-known that CD inclusion complexes have a so-called closed-loop system. “The guest molecule is very efficiently protected from external influences, such as decomposition, oxidation by air, polymerization, fading, etc. against. The complexes are stable until they are exposed to water. However, the smallest amount of water decomposes and the complexed substances are liberated.

The cosmetics industry uses a number of natural and synthetic fragrances to make the use of cosmetic products more pleasant. Spray powders and powders come in contact with air on a large surface of the fragrance and are therefore particularly resistant to oxidation. For this reason, e.g. no, or only costly expensive solutions can produce lemon and orange scented powder or powder.

There are also several volatile or environmentally sensitive degradable substances among the active ingredients used in medical swaddling powders, which may lose a great deal of their therapeutic properties during storage or use. Another role of CDs in honeybee powders is that the active ingredients of the honeysuckle powder and the fragrances, colorants, etc. of the carp powder used in cosmetics. enclosed in an inclusion complex, it protects them from adverse environmental effects.

In the dry state, CD inclusion complexes decompose under the influence of moisture. Nowadays, the skin's natural moisture is sufficient to slowly release the complexed fragrances and the anti-inflammatory and anti-inflammatory active ingredients from the complex and produce the desired effect.

Studies have been made to compare the commercially available powders according to the invention.

The fragrance content and fragrance content of commercially available baby honeydew powders were investigated by extraction by chornatography and thermofractography directly from the powders. We have found that these chewing powders contain very different but mostly small amounts of volatile matter (depending on the time between production and placing on the market). When stored in an open container at room temperature, the best quality chamomile-lanolin baby powder is practically completely lost in fragrance for 6 weeks.

Explanation of notations used in the tables ** '' 0 = no growth, ± = very weak growth, + = weak growth, + + = medium growth, + + + = strong growth.

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196 306

Beta-cyclodextrin inclusion complexes of lavender, sage, pine and rose oil were prepared. This is mixed with talcum powder to give a pleasant scent when rubbed onto the skin. The resulting compositions were stored at room temperature in open petroleum for 6 weeks. According to instrumental analysis, the fragrance content of the powders decreased below the measurement error limit, only in some cases it was possible to detect a small decrease of the most volatile minor components by gas chromatography.

In the production of CDs, the starch is digested and dissolved at a temperature above 100 ° C prior to enzymatic degradation of the starch. Subsequently, the starch is pre-hydrolyzed with alpha-amylase and the inactivity of the alpha-nylase is carried out by raising the temperature to above 80 ° C. After the degradation of the starch substitution rate by CTG, a mixture of alpha, beta and gamma CDs is formed in the conversion mixture. The enzymatic reaction can be shifted towards the formation of the desired CD by introducing into the conversion mixture a potential guest molecule that forms a water-insoluble inclusion complex on the desired CD. All of the guest molecules used for purpose c are disinfecting, removing excess by vacuum evaporation! It happens. The use of high temperature heaters and disinfectants as precipitants results in virtually no contamination of the CDs up to their microbiology, with less than 100 germs per gram of finished crystalline CDs.

The use of CDs is predominantly related to inclusion complex formation. Either the inclusion complex of the CD with some active substance is used, or the so-called inclusion complex. a blank CD is used, whereby the property of the complex baker is used.

In the snuff powder compositions of the present invention, both of the above complexing effects of the CDs are prevalent because CD complexes of the pharmaceutical agents and / or fragrances are used, on the one hand, and blank CDs, on the other. as a vehicle, it is able to complex the fatty acids that emerge from the pores on the surface of the skin, thus having deodorant, anti-inflammatory and anti-infective properties.

The vast majority of starch-degrading enzymes are unable, or only to a very limited extent, to cleave the cyclodextrin. In addition, there are significant differences between cyclodextrins. The smallest one, aira-cyclodextrin, is the least enzymatically attackable. The largest size, gamma-cyclodextrin, is relatively easily degraded enzymatically. Alpha-cyclodextrin is suitable for complex closure of the smallest molecules, whereas gamma-cyclodextrin is suitable for complexing of larger molecules (e.g., slcroids). The water solubility of each cyclodextrin is also highly variable, while 14 g of alpha-cyclodextrin, 1.8 g of beta-cyclodextrin and 22 g of gamma-cyclodextrin are soluble in 100 ml of water at room temperature.

In view of the above, the use of gamma-cyclodextrin in the powdered powder compositions of the present invention has been found to be less suitable due to its high solubility and minimal resistance to starch-degrading enzymes. Alpha and beta cyclodextrin seem to be very suitable for this purpose. These cyclodextrins can be ideal carriers for the carpet powder or the active components of the carpet powder.

BACKGROUND OF THE INVENTION The present invention relates to novel powders containing bioactive material, characterized in that they contain from 10 to 99% of the cyclodextrin. As a cyclodextrin, alpha- or respectively. beta CD or their polymers.

The invention further relates to a novel process. Protein powders containing bioactive material are prepared by the use of cyclodextrin as a filler, diluent, preferably alpha or pellet. beta CD or their polymers in amounts of 10-99%. According to a preferred embodiment of the process according to the invention, the active ingredient and / or the beneficial properties of the caraway powder are mixed with the caraway powder material in a CD inclusion complex.

The medicated sprays of the present invention may contain disinfectants, e.g. boric acid, sulfenylamide derivatives, antibiotics, salicylic acid, etc., or adjuvants (astringents), e.g. basic bismuth gall, tannins, zinc oxide, or keratolytic drugs.

The chewing powder compositions of the present invention for cosmetic purposes may contain various substances, preferably volatile substances, which result in the beneficial properties of the chewing powder. Lavender oil, pine oil, camphor, menthol, camomile oil, etc.

The invention is illustrated by the following non-limiting examples, which are not intended to limit the scope of the invention.

Examples

Example I

Chlorobutene Containing Powders 5 g Chlorobutyl g camphor-β-cyclodextrin inclusion complex (active substance content: 12%) g menthol beta-cyclodextrin inclusion complex (active ingredient content: 9.5%)

An aerosil mixture of 39.5 g of fine powdered beta-CD is prepared.

Chlorbutol can be used for antibacterial and antifungal properties, pruritus and other skin irritations.

Example 2

Protein bean powder g., Basic bismuth gallate. A mixture of 9 g.

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The baby powder prepared in this way is suitable for the treatment of eczema and inflammatory skin of infants.

Example 3

Zinc Containing Coating Powder Prepare a mixture of 10 g zinc undecanoate g undecanoic acid - beta - cyclodextrin inclusion complex (active ingredient content: 8.5%) g pine oil - beta - cyclodextrin inclusion complex (active ingredient content: 10%) g kaolin g beta-cyclodcxlrin .

Example 4

Paraformaldehyde Containing Fuming Powder Prepared with 5 g of paraformaldehyde g of lavender oil - beta - cyclodextrin inclusion complex (active ingredient content: 10%) g of g.

Example 5

Deodorants. ·! gum powder Add 0.1 g of hydroxyquinoline per gram of lavender oil - beta - cyclodextrin inclusion complex (content: 10%) to 100 g with alpha-cyclodextrin.

Example 6

Antibiotic-containing gum powder

500 mg bacitracin

250 mg neomycin sulfate

750 mg of sodium bicarbonate

A mixture of 500 mg of aerosil g of beta-cyclodextrin was prepared.

Example 8

Stylicylic Acid Containing Gum Salicylic Acid - Beta - Cyclodextrin Inclusion Complex (7% active ingredient)

0.5 g of aerosil is added to 5 g of zinc oxide beta-cyclodextrinine to 100 g.

Example 9 Foot Powder g Pentachlorophenol - beta - cyclodextrin inclusion complex (drug content: 9.5%) g salicylic acid - beta - cyclodextrin inclusion complex (drug content: 7%) g alum salt 5 g zinc oxide 5 g vanillin carbonate bcta-cyclodextr 100 g.

Example 10 Baby Breast Powder g Lavender Oil - Beta - Cyclodextrin - Inclusion Complex (content: 10%) g Boric acid g Beta-cyclodextrin A 48 g g.

/ /. Example 1 Sprinkle powder g Vitamin A - beta - cyclodextrin inclusion complex (active ingredient content: 9%) g of lavender oil - beta - cyclodextrin inclusion complex (active ingredient content: 10%) g of aerosil g of beta - cyclodextrin talc are added to 100 g.

EXAMPLE 7 Spray powder g lidocaine - base - beta - cyclodextrin inclusion complex (10% active ingredient)

0.5 g aerosil

A mixture of 0.5 g of sodium hydrogencarbonate and 74 g of β-cyclodextrin is prepared.

The coconut powder prepared in this way has a surface analgesic effect.

Example 12 Foot Spray Powder

89.5 g beta-cyclodextrin bead polymer

A mixture of 0.5 g of aerosil g talkurn is prepared cl.

The bcla-CD bead polymer used is a by-product of CDpolymer production.

5-50 pm fraction. The resulting carpet powder can be used as a foot powder or for treating rubber gloves.

196 306 ¹ Example 13 ¹

Csecsemckiütőpor

All proceed as in Example 2 except using a block of beta-CD block polymer instead of beta-CD.

Example 14 _1Q

Deodorant gum powder

All proceed as in Example 5 except that the alpha-CD foam polymer trace is used instead of alpha CD.

All of the listed powder powders must pass completely through a 250 micrometer mesh sieve.

Claims (7)

Claims 20 CLAIMS 1. A process for the preparation of a custard powder composition for therapeutic and / or cosmetic use. vehicle, diluent, carrier comprises a cyclodextrin or a polymer thereof and 10 to 99 mass% of a ₂ to 5, as well as biologically active ingredient (s) and / or odorant (s) and / or coloring agent (s) 90 - 1% by weight is mixed. A process according to claim 1 wherein the filler, diluent, carrier is beta-cyclodextrin or a polymer thereof. A process according to claim I, characterized by. as a filler, diluent, carrier, alpha-cyclodextrin or a polymer thereof. A process according to any one of claims 1 to 3, characterized in that the biologically active agent (s) are optionally used in the form of an eicodextrin inclusion complex. 5. The process according to claim 4, wherein the biologically active agent is an inclusion complex of lidocaine base, salicylic acid, pentachlorophenol, vitamin A and / or chamomile - blue oil - beta - cyclodextrin. Process according to any one of claims 1 to 3, characterized in that the fragrance and / or colorant (s) are used in the form of a cyclodextrin inclusion complex. 7. The process according to claim 6, wherein the perfume and / or coloring agent is selected from the group consisting of camphor, menthol, pine oil and / or lavender oil beta cyclodextrin inclusion.