HU199297B - Cosmetic and hygienic compositions comprising propolis cyclodextrin and process for producing the propolis cyclodextrin complexes - Google Patents

Abstract

The cosmetic and hygiene compositions of the present invention, preferably face-to-face foam, body lotion, moisturizing cream, oily cream, cream soap, toothpaste, mouthwash - from 0.1 to 20% by weight of cC, I, and / or K-propolis cyclodextrin - contain complexes and known excipients and carriers. According to the invention, the cyclodextrin-propolis complex is prepared by the addition of oC-, O or γ-cyclodextrin, or a mixture thereof, or a solution of 2-30% by weight thereof, with a dry matter content of 2-25% by weight, 2-30% by weight. the resulting crystals are separated. EN 199297 A Scope of the description: 6 pages without drawing -1-

Description

The present invention relates to the preparation of propolis-cyclodextrin complexes and to cosmetic and hygienic compositions containing this propolis-cyclodextrin complex. The formulations contain from 0.1 to 20 tX oC-, β- and / or γ-propolis cyclodextrin complex and inert excipients and preservatives.

The propolis cyclodextrin complex is prepared by extracting from 2 to 25% by weight of an extract of 2 to 25% by weight of an oC-, β- or γ-cyclodextrin or a mixture thereof or a solution thereof in an amount of 2 to 30% by weight. and the resulting crystals are collected.

Propolis produced by bees is soluble in solvents and can be successfully used in the cosmetic industry due to its advantageous biological properties. Its use is facilitated by complexing the propolis with cyclodextrin.

The crude propolis is a solid material that is highly heterogeneous in appearance and looks like a poor soil. Crude propolis is known to contain resins, waxes, as well as a variety of insoluble, non-absorbable ballast, sometimes insect debris and other rotting organic materials, in addition to its effective (anti-inflammatory, bactericidal, etc.) materials.

A number of processes are known for extracting a concentrate of active substances by extraction with various solvents. These concentrates, depending on the solvent, the recovery process and the concentration, are dark brown oily viscous solutions containing only the components in the swollen state and not in solution.

The direct incorporation of the concentrates into cosmetic formulations is inappropriate because of the large amount of phenolic compound present in the material which, when oxidized to polyphenol, partially loses its effect and causes a degree of discoloration that renders its use impossible. In spite of known bleaching techniques, the composition has an intense brown color, and when used, these intensive coloring components discolor the skin as well as the textiles in contact with it by releasing the propolis components. Propolis and its effective extract are photosensitive, heat sensitive, difficult to dissolve and difficult to absorb.

Despite all these disadvantages, many propolis-containing cosmetics are marketed around the world, due to the above-mentioned difficulties, they are marketed with low propolis content and are usually very dark in color.

Formulation attempts have also been made in which formulations containing 0.5 to 2.0 tX of propolis have been prepared using limited amounts of additives having adverse properties. (Gelatin, gummy substances, polyvinyl pyrrolidone, etc.)

Stirring with Na citrate in hot water gives a solution containing 1.4% by weight of propolis. (French Patent 2,374,030 (1978)). Gelatin acacia by microencapsulation of rubber in the presence of olive oil can provide a good antimicrobial agent. [Acta Pharm. Yugoslavia. 1981. 31 (1) 27-32). The propolis extract can be mixed with an alcoholic solution of polyvinylpyrrolidone by evaporation with polyethylene glycol and then granulated with 80 tX sorbitol syrup to provide pharmaceutical and cosmetic agents (Romanian Patent 67,036 (1978)). 2 tX propolis stearate polymerate can be obtained by boiling the propolis with Mg-glyconate and filtering off the material. [Danish Patent 133 584 (1976)]

In our experiments, it has surprisingly been found that by inclusion complexing with cyclodextrins, an efficient mixture of propolis, otherwise similar in molecular size and molecular weight, with a similar polarity, yields a homogeneous mixture of inclusion complexes which have the same ratio of components. Propolis, as a multicomponent product, is not suitable for the preparation of a homogeneous crystalline inclusion complex. Because of such a large number of components, there is no hope of producing and identifying crystalline complexes of each component individually. However, two-dimensional thin layer chromatography confirmed that all effective components can be incorporated into inclusion complexes.

Inclusion complexes, on the one hand, stabilize the active ingredients, and their secondary effect is to increase the bioavailability of the product due to the increased hydrophilicity. Cyclodextrins are prepared from starch by enzymatic conversion, and their oral or external application does not present any toxicological problem. Cyclodextrin inclusion complexes of a wide variety of drugs have been described.

Cyclodextrins are also useful for stabilizing aroma compounds. Such products are commercially available. Many ideas for the use of cyclodextrins in cosmetic formulations have been described but have not yet been produced in practice.

Oxidable, heat and photosensitive compounds, complexed with cyclodextrins, can be protected from oxidation, further degradation, improve heat and light stability, increase storage, stability, and even improve pH tolerance.

After complexation, the propolis components lose their coloring properties of leather or fabrics. As will be apparent from the examples describing the details of the present invention, propolis formulated with cyclodextrin in a wide variety of cosmetic formulations (

GB 199297 Pan, castor powder, lotion, face lotion, mouthwash, etc.) can be used without difficulty.

Surprisingly, it has been found that the propolis components formulated with cyclodextrins do not migrate in the lipid medium. Thus, for example, the outer surface of the soap is not discolored better by heat generation; the soap remains completely homogeneous and has a pleasant color even after longer storage. The homogeneity of the soap is perfect.

Among the effective components of propolis are the following:

- acids, phenols (caffeic acid, cinnamic acid, forulic acid, ferulic acid, fatty acid and their esters, etc.)

- flavonoids (flavonones, flavonols, fovones, etc.)

- organic acids (eg benzoic acid),

- aromatic aldehydes (eg vanillin, isovaniline)

- other components (amino acids, lactones, trace elements, vitamins).

Taking into account the molecular size of these compounds, as well as the cavity size of cyclodextrins (6-8-10 A in diameter), molecular weights of 978, 1135, 1278 (cC-, β-, γ-cyclodextrin), molecular encapsulation, thus releasing the active ingredient per molecule, provides instantaneous rapid absorption, while at the same time gradual sustained release is expected. Various cyclodextrins were used to form the propolis-cyclodextrin complex

- cC-cyclodextrin,

- α-cyclodextrin,

a mixture of β- and γ-cyclodextrin, and

- a cyclodextrin conversion mixture (a crude product of the manufacture which contains, in addition to mixtures of cyclodextrins, linear dextrins).

The propolis-cyclodextrin complex was analyzed by thin layer chromatography and found to have the same two-dimensional chromatogram of the propolis extract and the complexes. In addition, the moisture content and propolis content of the product were determined. The following method was used for the content determination and for thin layer chromatography:

Determination of propolis content

1. Measure the bound water content of the pre-dried (air-dry) product (air dry) by the Kari Fischer method. This varied between 7.6-8.0% by complex. Subsequently, 25 mg of the product are dissolved in 25 ml of 50% methanol and, after 5-fold dilution, UV absorption at max = 29512 mm is measured in a 1 cm cuvette.

Determine the propolis content of the samples on the basis of the calibration of the propolis extract in 50 tX ethanol taking into account the respective water content. Its value varies from 7.8 to 12.0 tX, depending on the cyclodextrin used and the manufacturing technology used.

2. The determination of the active ingredient content can also be carried out by solvent extraction. 1.0 g of propolis cyclodextrin complex is dissolved in 100 ml of water with stirring at bzúLu to give an opaque solution which is extracted with 2 x 35 and 1 x 45 ml of diethyl ether with 5 g of NaCl. The ethereal phases are combined, concentrated in vacuo at 20 ° C and the weight of the extract is determined on an analytical balance. As a control, it is performed after drying of the starting propolis extract.

Quality control of propolis - cyclodextrin complexes

Silica gel GF254 (Merck) was used, and the development solvent was a mixture of benzene-ethyl acetate 95 + 5 and 90 + 10, respectively.

In the two - dimensional run, a 75 + 5 + 20 mixture of cyclohexane - glacial acetic acid - ethyl acetate is used for the second direction development.

The components were developed under 254, 360 nm UV light, followed by the following reagents:

- 10% by weight of phosformolybdene dea in ethanol (105 ° C for 5 minutes)

- 5 tX vanillin sulfuric acid - in ethanol (105 ° C for 10 minutes)

- 5 tX anisaldehyde sulfuric acid in ethanol (105 ° C for 10 min)

- 5tX solution of SbCk in chloroform (110 ° C for 10 min)

- with 3% FeCh solution (phenol)

Propolis, formulated as an inclusion complex with cyclodextrins, has been formulated in a variety of cosmetic product groups.

Cyclodextrin-propolis complex can be used to produce stable cosmetic formulations. These formulations are substantially more stable than the known propolis-containing formulations and exhibit a significantly better effect.

The compositions of the invention contain from 0.1 to 20% by weight of the oC, β, and / or γ-propolis-cyclodextrin complex and auxiliaries commonly known and used in the preparation of cosmetic compositions.

Carriers include stearin, paraffin oil, sunflower oil, glycerol, water, ethanol, fatty alcohol or soap shavings.

Among the excipients are formulation auxiliaries, preferably carboxymethylcellulose; emulsion stabilizers, such as Carbopol (carboxyvinyl polymer) or hostacerin (which is a polyacrylate-35).

HU 199297 A rium salt); thickening agents such as silica or carboxymethylcellulose; preservative ethers such as butylhydroxytoluene, phenopipe (a mixture of methyl, ethyl, propyl, butyl esters of parahydroxybenzoic acid dissolved in phenoxyethanol); emulsifiers such as amphisol (diethanolamide cetyl phosphate), cremophor (a mixture of cetyl alcohol and stearic alcohol), Tweent (sorbitan fatty acid ester ethyl) and Spant (sorbitan fatty acid ester). In addition, perfumes and colorants known in the art may be used in the compositions.

Propolis-cyclodextrin complexes as well as methods of preparation. but without limiting the scope of protection to these, the following examples illustrate.

Production examples

Preparation of inclusion complexes

Example 1

Dissolve 600 g of β-cyclodextrin in 6 liters of water at 58-60 ° C and slowly add dropwise a solution of 62 g of propolis in 300 ml of 96% ethanol with constant vigorous stirring. The reaction mixture was cooled to 15 ° C with constant stirring for 5 hours after the addition of the propolis solution. After crystallization at 0-5 ° C for another 14 hours, the product was recovered by filtration. It is air-dried at room temperature or with flowing warm air (40-45 ° C) to constant weight, crushed and sieved through a 450 µm screen. 610 g of a pale yellow fine crystalline powder having a propolis content of 7.8% are obtained.

Example 2

600 g of β-cyclodextrin are suspended in 5 liters of water with vigorous stirring at 20 ° C. A solution of 62 g of propolis in 300 ml of 96% ethanol is added slowly dropwise.

After stirring vigorously for 24 hours at 20 °, the crystalline product is filtered, dried and sieved. 630 g of a pale yellow, odorless crystalline product having a propolis content of 7.8-8.0% by weight are obtained.

Example 3

All proceed as in Example 1 except that propolis is added without prior dissolution (90% ethanol).

Example 4

All proceed as in Example 1 except that the reaction mixture is not filtered but evaporated to dryness in vacuo or freeze dried.

Example 5 g of β-cyclodextrin is wetted with 5 mL of water and kneaded with a solution of 6.2 g of propolis in 10 mL of 96% ethanol until a dry, powdery product is obtained. Products weight 6, 2.6 g, propolis content

9.5%.

Example 6

In all cases, it is the same as that of Example 1, except that β-c-cyclodextrin is replaced by γ-cyclodextrin.

Example 7

It is identical in all embodiments to that of Example 1 except that a mixture of cC, β and γ cyclodextrins is used in place of β-cyclodextrin.

Example 8

Identical to the embodiment of Example 1 except that the crude conversion mixture obtained in the manufacture of cyclodextrin is used instead of β-cyclodextrin to prepare the inclusion complex.

Example 9

In a 250-L speed mixer, 150 L of 10% w / w solution of β-cyclodextrin was prepared at 60 ° C with vigorous stirring, jacket heating, and temperature control.

To the solution was added 5 liters of alcoholic propolis extract (dry matter content 31%, total flavonoid content 14.23% by weight, propolis content 25% by weight) at 60 ° C with constant vigorous stirring. After another 2 hours of vigorous stirring and maintaining the temperature at room temperature, the heating was stopped, the material was cooled to about -5 ° C, filtered through a vacuum filter, gently max. It was dried at 40 ° C.

The product is 12.5 kg propolis-β-cyclodextrin complex with a total flavonoid content of 13.5% (expressed as routine).

Propolisztartalom; 20.5%.

-411U 199297 A

Example 10

Using the technology described in Example 1, starting from 600 g of oC-cyclodextrin, 580 g of oC-cyclodextrin-propolis complex was obtained with 5 tX propolis content. A 5 tX propolis solution was used.

11-17. Examples 1 to 4 show the composition of some formulations using the propolis cyclodextrin complex. In addition to the pleasant dark coloring of propolis, the use of the complex has virtually eliminated the ability to contaminate textiles and improve its absorbency, thermal and durability (incubation at 37 ° C did not discolour within 24 hours instead of 24 hours). formulations) and improved odor stability (for example, cream soap retains its pleasant fragrance until use, like other formulations).

Example 11

Foam for face

Tween 60 (sorbitan fat

etoxilátum acid ester) 1.80 tX (Emulsifier) Amphisol (diethanolamide cetyl phosphate) 2.60 tX (Emulsifier) stearin 1.40 tX IPM (isopropyl myristate) 4.50 tX starched sunflower fat 0.40 tX paraffin 2.00 tX propolis -? - cyclodextrin complex 2.00 tX phenonip (a mixture of methyl, ethyl, propyl and butyl esters of p-hydroxybenzoic acid dissolved in phenoxyethanol) (Preservative) 0.15 tX fragrance 0.30 tX water 82.85 tX 100.00 tx Example 12 Lotion Tween 60 3.50 tX (emulsifier) span HZ (sorbitan fatty acid ester, 0.40 tX (emulsifier) alfol 11-16 (blend of 11-16 carbon atoms fatty alcohols) 3.00 LX

1ΡΜ 4.00 tX hardened sunflower fat 2.00 tX propolis-0-cyclodextrin complex 2.00 tX glycerol 2.00 tX carbopol 940 (940 molecular mass carboxyvinyl polymer) (Emulzióstabilizálószer) 0.40 tX fragrance 0.30 tX phenonip 0.15 tX (Preservative) water 82.25 tX

100.00 tX

Example 13

Ilid comes to me in awe

Cremophor A 6 (0) stearyl and cetyl alcohol

(emulsifier) 2.80 tX amphisol 0.70 tX (Emulgelélószer) alfol 11-16 6.00 tX cetiol V (cetyl alcohol) 6.00 tX beeswax 1.00 tx hardened sunflower fat 3.00 tX BHT (Butylhydroxytoluene) 0.01 tx (Avasodásgátló) propolis-uh-cyclodextrin complex 2.00 tX fragrance 0.30 tX phenonip 0.20 tX (Preservative) carbopol 940 0.24 tX (Emulsion stabilizer) water 77.75 tX 100.00 tx

Example 14 Night cream hostacerin WO (polyacrylate sodium salt) 9:30 tx (The gelling agent) span 0.70 tx (Emulsifier) beeswax 2.80 tx paraffin 15:00 tx IPM 6:00 tx BHT 0:01 tx (Avasodásgátló) glycerol 5:00 tx phenonip 0:20 tx (Preservative) fragrance 0:30 tx propolis-cyclodextrin complex 2:00 tx water 57.69 tx 100.00 tx

HU 199297 A

Example 15

toothpaste

Example 18

cream Soap

5 fragrances 1:50 t% tallow (Ethoxylated) 0.80 t% propolis-.alpha.-fl-cyclo dextrin complex 15:00 t% 10 soap stabilizers 0:30 t% galakol on white 0:20 t% 20% soap shavings 82.20 t%

100.00%

15 Example 19 Lotion 20 Example 12 use composition- after all, with the difference that that 0.5 massX oC- -β-cyclodextrin propolis complex and 83.75

eocal U (ground calcium

carbonate) 22:00 t% (Abrasive) dicalcium phosphate 17:00 t% CMC (carboxymethylcellulose) (abrasive) 1:00 t% glycerol 11:00 t% sorbitol 70% wacker HDK N20E (colloid 6:00 t% silica) (Thickening agent) sarcosyl NL 30 (30% 2:00 t% sunflower fatty acid sarcosine) 8:00 t% Na lauryl sulfate 0.90 t% nipagin (methyl para) (preservative) 0:10 t% sacharin 0:10 t% fragrance propolis-beta-ciklodexlrin 1:20 t% complex 2:00 t% deionized water 28.70 t% Example 16 Mouth wash 100.00 t% alcohol 96% 78.00 t% menthol 0:15 t% sacharin propolis-a-cyclodextrin 0:02 t% complex 2:00 mass- fragrance 0.80 1% water 19:00 t% Example 17 cream Soap 100.00 t% fragrance 1:50 t% tallow alcohol (ethoxylate) propolis-o-C-cyclo 0.80 t% dextrin complex stabilizer bar 1:00 t% (Ethylene diamine tetraacetate) (Avasodásgátló) 0:30 t% galacol white (dye) 0:20 t% 20% soap shavings 96.20 t%

100.00% w / w water is used.

Example 20

Night Grease 30

The composition of Example 14 was used, except that 6 massX oC, β- and β-cyclodextrin mixture complexes and 53.69 tX of water were used.

Claims (2)

CLAIMS 1. A process for the preparation of propolis cyclodextrin complexes, wherein the amount of 2- Reaction is carried out with a propo45 flour extract of 30% by weight and the resulting crystals are separated. 2. Cosmetic and hygienic preparations - preferably facial foam, lotion, moisturizing cream, oily cream, cream soap, toothpaste, mouthwash - in which the carrier, preferably stearin, paraffin oil, sunflower oil, glycerol, water, ethanol, fatty alcohol or soap shavings, if desired, cellulose, An emulsion stabilizer, preferably a carboxyvinyl polymer, a preservative, preferably butylhydroxytoluene, an emulsifier, preferably diethanolamide cetyl phosphate, and a coloring agent. there is volatile matter, 60 that the formulations contain from 0.1 to 20% by weight of the?,? And / or? -Cyclodextrin complex produced according to claim 1.