The method of obtaining kremnijorganicheskih microcapsules to create medical, cosmetic preparations

 

(57) Abstract:

The invention relates to biotechnology and can be used in biology, pharmacology, cosmetics industry, veterinary and food industry. The invention lies in the fact that to obtain kremnijorganicheskih microcapsules before mixing the lipophilic and hydrophilic components in the lipid fraction enter the allowable amounts of organosilicon polymer compound, and dispersing is carried out in a rotary cavitation installation of high shear effort and powerful acoustic phenomena of sound and ultrasound range, providing a subtle redistribution of particles at the moment of their passing through the installation. The invention provides for the receipt of phospholipid vesicles with certain parameters when using industrial dispersal devices. 1 C.p. f-crystals, 3 ill.

The invention relates to biotechnology and can be used in biology, pharmacology, cosmetics industry, veterinary and food industry.

Drugs based on liposomes or vesicles can be used in biology, pharmacology and food industry is of therapeutic activity of drugs.

Preparations on the basis of phospholipid vesicles (MGR) appeared relatively recently and in a short time became widespread, first in medicine and then in cosmetics. The impact MGR due to the possibility of their deep penetration into the tissue. In this way it can be ensured depth shipping is not only good for the body lipids that normally make up the membrane of the microcapsules, but also other substances that are in their internal volume.

Depending on the method of obtaining phospholipid vesicles (MGR) may have different lay-up (one or more lipid bilayers). In cases when it is required to be enclosed in the liposome substance with a high molecular weight (for example, when solving problems of genetic engineering by incorporation of DNA molecules), are large liposomes, including multilayer. In other cases, it is usually preferable small odnolineynye vesicles.

Of previously developed methods of obtaining liposomes are known a method of obtaining a liposomal composition (see RF patent N 2014070, class A 61 K 9/127, 1991).

The disadvantage of this method is that it does not obtain liposomes having small dimensions. Clucene liposomal composition (see European patent N 0130577, class A 61 K 9/50, 1989), comprising mixing components of the liposomal membrane with non-volatile water-soluble physiologically acceptable organic solvent and dispersing the resulting mixture in an aqueous medium using conventional agitators.

The resulting liposomes are of relatively large dimensions 2500 nm, which is the main disadvantage of this method.

The closest in technical essence of the present invention is a method of obtaining a liposomal composition comprising forming a mixture containing at least one component of the liposomal membrane, water and additive, the dispersion of the mixture, is that as an additive is used or submicromolar substances that are not soluble in water and in an organic solvent or swelling in water of the polymers, or liquid that is not miscible with water and other components of the mixture (patent RF N 2104691, MKI7A 61 K 9/127, 9/50, 9/66, BI N 5, 1998).

The disadvantage of this method is that when an industrial scale, there are several challenges:

a) for stable reproducibility of the method requires special equipment (mixing the mouth of all lipid components, in order to avoid their aggregation in an acidic environment;

C) use only distilled water because the system is very sensitive to the presence of salts, even which are water-alcohol extracts trace.

In addition, in some cases, the additive must be removed where used Aerosil or perftoran. The second variant of the method, which uses the swelling polymer zacapa, vesicles are original in an acidic medium by neutralizing medium is the unfolding of the polymer, resulting in the formation of a gel-like substance. This is useful for certain tasks, but does not provide the versatility.

Object of the present invention to provide a phospholipid vesicles with certain parameters when using industrial dispersal devices. Kremnijorganicheskie single-layer microcapsules containing a biologically active substance (BAS) and with aggregative stability in environments with a pH range from 5.0 to 9.0 and salt content in the aqueous phase to 0.1% (mainly Ca++and Mg++) are highly efficient and versatile to create medical, cosmetic preparations.

In ispolzuya medical, cosmetic, pharmaceutical, veterinary, dental, and other drugs.

The technical result is achieved by the fact that before mixing the lipophilic and hydrophilic components in the lipid fraction enter the allowable amounts of organosilicon polymer compound, and dispersing is carried out in a rotary cavitation installation of high shear effort and powerful acoustic phenomena of sound and ultrasound range, providing a subtle redistribution of particles at the moment of their passing through the installation.

In the aquatic environment add trace ethylenediaminetetraacetic acid (EDTA) production. As a regulator of lipid phase using organosilicone compounds, such as craniometriques, or polyethylsiloxane, or alkylacrylate that allows you to achieve homogeneity of lecithin, reducing its viscosity and facilitate its subsequent mixing with other lipids. Kremnijorganicheskie compounds before mixing add in the lipid phase of the allowable amounts. As dispersing devices use the rotary cavitation installation (CGS), which both trasloco processing it. The result is the formation of small single-layer vesicles with an average size of 20-60 nm.

In the proposed method of obtaining kremnijorganicheskih microcapsules to create medical, cosmetic preparations, including the formation of a mixture containing lipid phase, water and biologically active substances (BAS) in the aquatic environment, as the stabilizer is added in amounts of EDTA. EDTA - ethylenediaminetetraacetic acid is used in the form of a disodium salt dihydrate (Trilon B) as a chelating agent, anticoagulant blood and stabilizer in food products, for the production of liquid Soaps and shampoos, plant protection, water softener / Chemical encyclopedia. Scientific publishing house of the Great Russian encyclopedia. M., 1999. So 5. S. 988). The use of trylon B as a water softener and when using the rotary cavitating dispersion can get products for medicine, cosmetics and veterinary lower energy costs (very expensive distillate) without losing quality. As a stabilizer of the lipid phase, the homogeneity of the lecithin and the ease of its subsequent mixing with other lipid type in a valid kolichestvoparkov, which provides a high-speed dispersing a mixture of water and lipid phases with simultaneous low frequency ultrasonic treatment.

As organosilicon compounds used silicon octamethylcyclotetrasiloxane, or polyethylsiloxane, or Dimethicone. Silicones are widely used to improve the organoleptic and aesthetic characteristics of cosmetic products, in particular sunscreen preparations. There is an assumption that in addition to improving the chemical characteristics organosilicon reinforce sun protection properties of drugs with the same content of active substances. The use of a mixture of lecithin /silicone in different ratios (from 1:1 to 1:0,25) allows to obtain a uniform thin lipid film, which is very important in the formation of membrane structures.

The proposed method allows the use of lipids without organic solvents, due to the introduction of organosilicon compounds.

The essence of the invention is to use a rotary cavitation installation (CGS) for minor single-layer vesicles. The use of CGS allows you to combine two isostructural a simple and robust design, combining powerful generator of hydro-acoustic oscillations and effective mixer that allows you to obtain a finely dispersed emulsion of water and fuel mixtures.

The application of the method of the rotary cavitation processing to obtain kremnijorganicheskih microcapsules allowed to obtain large volumes of suspensions of vesicles of different concentrations on lipid and with different composition of biologically active substances in a very short period of time, 5-10 minutes of operation 10 - 50 l liposomal suspension. The installation allows metered through the holes to enter both hydrophilic and lipophilic compounds to stop the process if necessary, change the settings MOB by adjusting time and temperature regimes.

CMR allows the use of the aqueous phase with different rigidity index (from distilled to water).

The capacity of the plant allows the use of low water purification. To stabilize the lipid ingredients in the fat mixture is introduced a small number of organosilicon compounds (2%).

In Fig. 1 shows the General scheme rotowire-cavitation installation (CGS).

In Fig. 2 electronic gel, the amount of the marker 2000 nm, b - external and internal structure of the gel particles, the amount of the marker 250 nm.

In Fig. 3 - e picture of the microcapsules of the gel balm, obtained by the method of negative contrast.

The apparatus comprises a motor 1, the capacity for the introduction of the lipid fraction 2, the capacity for the introduction of hydrophilic substances and solutions with 3 valves regulating the feed rate of the lipid phase 10 and mortars BAS 9, the camera prior distribution 4, the camera sound 5, the rotary cavitation mill 6, the formation area of cavitation phenomena 7, the device for preparation of ready-made forms 8.

According to the first version the problem is solved by the fact that the method of obtaining the liposomal composie using RKU is distilled water with a certain amount of lipids, strictly balanced composition. Thus formed microcapsules for drug treatment-and-prophylactic actions with application in dentistry.

Before mixing lipid fractions add organosilicon compounds in the vessel 2. Control valves 9 and 10 allow the jaw to enter the lipids in the camera pre-film PE the STI 3000 rpm fall into the camera sound 5. The rotation of the rotor provides a mechanical dispersion of a mixture of lipids in the aqueous phase 5 and education sonar and ultrasonic vibrations.

CGS provides two methods simultaneously: dispersion and ultrasonic shear phenomena provide a subtle redistribution of particles at the moment of their passing through the installation.

Specifications RKU.

Performance on the water when the inlet pressure of 0.1 to 1.5 MPa and 3.6 to 14.4 m3/PM

Allowable inlet pressure 15 MPa.

Permissible operating temperature of the treated fluid - 0-90oC.

The kinematic viscosity of the medium to 140 cSt (mm2/s).

The total sound pressure level in the cavity of the camera sound 180-200 dB.

The power of the motor 3-5 kW.

Weight 18 kg

Dimensions 870350325 mm

Ample opportunities CGS can be used to improve the efficiency of current serial production lines and newly created.

Depending on the specific features of technological process CGS allows optimum performance, power and frequency acoustic copozitia lecithin with polyethylsiloxane. In the finished composition is injected lipid ingredients: oil, oil extracts, essential oils.

2. Prepare solutions of water-soluble substance.

3. The carbopol (copolymer of acrylic acid poliamidowych esters of PENTAERYTHRITE) soaked in water for 30' to swell, and then mixed in the device 8 and is introduced hydroaxe Na or triethanolamine for gelation and pH regulation of the environment.

4. When running the install through the camera redistribution in the camera sound 5 go lipo - and hydrophilic ingredients and processed in the course of time, the corresponding regulations (from 2 to 10 min).

5. Willing suspension kremnijorganicheskih microcapsules injected into the polymer base and mix until smooth.

The proposed technique allows the preparation to form kremnijorganicheskie microcapsules in flow mode, to prevent the use of unauthorized additives, to minimize the use of organic solvents (used only pure ethyl alcohol at a concentration of 0.5% or aqueous-alcoholic extracts permitted for use).

In certain cases it is possible to use microscopic particles not rusticators number of dispersing particles dramatically increases the surface area, which may be the formation of liposomes.

In the result of the influence of acoustic vibrations with mechanical dispersion is the process of formation of liposomes. New results are obtained using CGS without the use of other additives, and received small odnolineynye vesicles, the size and lay-up which was monitored by electron microscopy.

Further illustrated by the examples of the implementation of the various options of method of obtaining kremnijorganicheskih microcapsules to create medical, cosmetic preparations.

Received hygienic, certificates, clinical trials on the effectiveness of drugs.

Example 1. Care cream for the face.

The lipid phase, aqueous phase. Water-alcohol extract is introduced into the lipid phase, while BAS part kremnijorganicheskih microcapsules. The resulting gel-balm-repairbuy. Composition: microcapsules in a gel base containing a complex of lecithin, milk Thistle, olive oil, multi complex of antioxidants from tomato and dioskoreya deltoid, essential oils of lemon, apemantus systems, stimulates the process of reparaci and anabolic activity. Is the preparation. Application: for care of annoying, inflamed and exposed to heat, ultraviolet or ionizing radiation skin. (Catalog of products "MIRRA-M" M, "MIRRA-LUX, 1999,12 C.).

Prepare lipid mixture containing necessarily lecithin and polyethylsiloxane.

Example 2. Care cream for the face.

The lipid phase, aqueous phase. Hydroalcoholic extracts are introduced into the lipid phase and the gel base in a free form. Get the gel-tonic for oily skin. In the lipid phase is entered zinc (Zn0) and sulfur (S) in the amounts and in the internal volume of the microcapsules - Supplement - ecolect (Handbook on company products "MIRRA-M, M, 1998, T. 1, S. 33, product Catalog "MIRRA-M" M, "MIRRA-LUX, 1999, 20 C.).

Example 3. Hair gel.

The lipid phase, aqueous phase. Hydroalcoholic extracts are introduced into the lipid phase and the gel base in a free form. (Handbook on company products "MIRRA-M, M, 1998, T. 1, S. 33).

Example 4. Gel silver.

In this way the obtained basis for the treatment and prevention of drug Den tonic to care C is aktivnosti Silver gel" production company "MIRRA-M", Scientific report, M., Institute of beauty).

The proposed method allows to obtain cosmetic sunscreen Gelios, preventive veterinary remedy gel-balm antiseptic stimulant (A) BASSET, gel, balms for the hair.

Depending on the target product additive can be removed after surgery dispersion.

In industrial conditions, the formation and dispersion of the mixture it is advisable to do in running mode.

1. The method of obtaining kremnijorganicheskih microcapsules to create medical, cosmetic products by forming a mixture comprising mixing lipids with water-soluble additives and polymers and dispersion, characterized in that before mixing the lipophilic and hydrophilic components in the lipid fraction enter the allowable amounts of organosilicon polymer compound, and dispersing is carried out in a rotary cavitation installation of high shear effort and powerful acoustic phenomena audible and ultrasonic ranges, providing a subtle redistribution of particles at the moment of their passing through the installation.

2. The method according to p. 1, oxen, or polyethylsiloxane, or Dimethicone.

 

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