Method for preparing drug preparation of immunomodulator for treating severe purulent-septic and autoimmune diseases

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, and concerns a method for preparing a drug preparation of an immunomodulator for severe purulent-septic and autoimmune diseases on the basis of a peptide fraction recovered from mammalian spleen tissue or cells (particularly swine or cattle spleen). Substance of the invention: there are mixed biologically active substance - that is a peptide fraction recovered from mammalian spleen tissue or cells with a substance preventing protein molecule coagulation, and an antibiotic. Gelofusine is used as the substance preventing protein molecule coagulation.

EFFECT: invention provides the high therapeutic effect in preventing and treating the purulent-septic and autoimmune diseases.

1 dwg, 1 ex, 3 tbl

 

The present invention relates to medicine, namely to preparative biochemistry, pharmaceutical industry and biotechnology and concerns a method for obtaining a medicinal product on the basis of peptide fractions isolated from tissues or cells of the spleen mammals (in particular, the spleen of pigs or cattle), with immunostimulatory activity.

A method of obtaining a medicinal product on the basis of peptide fractions isolated from tissues or cells of the spleen mammals possessing immunostimulatory activity.

(EN 2152219 C1, AC 35/28, AK 38/02, 2000)

In the known method was attempted to maintain the solubility of the drug (prevention of coagulation of protein molecules) using drug relational representing the gelatine hydrolysate, and an antibiotic.

The present invention is the development of a medicinal product, which has a higher immunostimulating action with the activation of cellular and humoral immunity, providing increase of specific and nonspecific resistance of the organism in the prevention and treatment of severe forms of septic and autoimmune diseases.

The technical result is obtained when using the claimed invention, is expressed in high therapeu the practical effect in the prevention and treatment of severe forms of septic and autoimmune diseases.

To achieve the technical result, in the method of obtaining the drug, possess immunostimulatory activity, for the treatment of severe forms of septic and autoimmune diseases, comprising mixing the biologically active substance is a peptide fraction isolated from tissues or cells of the spleen mammals, with a substance that prevents coagulation of protein molecules, and an antibiotic, wherein as a substance that prevents coagulation of protein molecules, use gelofusine.

Gelofusine mixed with a solution of peptide fractions of spleen in the manufacturing process of the medicinal product. An integral part of way to obtain method is the preservation of the high solubility of the drug and, consequently, biologically active peptides, including cytokines.

Gelofusine is a 4% aq succinylamino gelatin (also known as a modified liquid gelatin) in 0.9% sodium chloride solution with average molecular weight of 30,000 Da. The relative viscosity of R-RA 1,9 at 37°C, colloid-osmotic pressure of 34 mm RT. Art. as a Result of succinylcholine gelatin molecules become more negatively charged and therefore more lessons. Due to the form of gelatin molecules produces a greater surround effect, che is neaktivirovannye protein chain with the same molecular weight.

Gelofusine differs significantly from gelatinosa (in the prototype). Therapeutic properties gelofuzina have significant advantages (see table 1).

Table 1
Comparative characteristics of Gelofuzina and Gelatines
Main featuresGelofusineGelatin olBlood plasma
Composition4%p-p of the modified liquid gelatin8%aq partially hydrolyzed gelatin
Osmolarity, mOsm/l274371280-290
Srma. weight3000015000-20000
Colloidal osmoticheskoe pressure (CODE), mm RT. Art.3416-2116-24
Will Nesci effect Surround effect %10060
duration (hour)3-41-2
Na mmol/l154162136-143
CA mmol/l<0,49,382,4-2,6
To mmol/l<0,40,43,5-5,0
C1 mmol/l12016296-105

Relational has a wide range of molecular mass distribution (MMD) is from 5 to 100 KD. It explains:

its low direct volemic effect (about 0.5) and the danger of the leakage of the active substance in the interstitial space;

weak influence of gelatinous CODE on the blood plasma of the patient;

- short half-life (1-2 h);

a relapse of the original hemorheological disorders (aggregation of platelets, sequestrat what I erythrocytes) after a short improvement of circulatory homeostasis;

- frequent anaphylactoid reactions;

the excess calcium in gelatinase (>8 mEq/l), which excludes the use of this drug in combination with citrate transfusion environments, some medicines.

Therefore, the drugs of choice at the present time believe infusion medium on the basis of modified (succinylcholine) liquid gelatin (modified liquid - MLG) for example is available for domestic Clinician Gelofusine B. Braun. Such plasma substitutes are:

- low range molecularmass distribution with the average MM to 40 KD.

- high CODE that may exceed CODE blood plasma.

- high direct volemic effect (up to 1.0) low possibility of the leakage of the active substance in the interstitium due to the shape of its molecule.

- a large part of the active substance preparations MLG (75%) is excreted via the kidneys, and minority through the colon;

- 10% of the active substance MLG can be metabolized;

- solutions MLG safe in relation to their effects on hemostasis, so it is widely used to fill in operative blood loss and compensation exposureand amounts of plasma at high therapeutic plasmapheresis;

- anaphylactoid reactions to gelofusine virtually absent.

The study (described below), based on a comparative analysis of the arr is sausages sediment, proves that gelofusine has a more pronounced ability to prevent coagulation of the peptide molecules in the prepared drug and, consequently, improve therapeutic effect in the prevention and treatment of severe forms of septic and autoimmune diseases.

Spent an analysis of the prior art, including searching by the patent and scientific and technical information sources, and identify sources that contain information about the analogues of the proposed method of obtaining drug has allowed to establish that the petitioners have not found a similar, characterized by signs, identical to all the essential features of the claimed method.

Therefore, the claimed method of obtaining a medicinal product meets the criterion of "novelty."

To verify the conformity of the method of the prior art, the applicants conducted an additional search of the known solutions to identify signs that match the distinctive features of the prototype of the characteristics of the claimed invention.

The search results showed that the claimed invention not apparent to the expert in the obvious way from the prior art, certain applicants have identified no impact envisaged the essential features of the claimed medicinal drugs the ATA transformations to achieve a technical result.

Therefore, the claimed invention meets the criterion of "inventive step".

The criteria of the invention "industrial applicability" is confirmed by the fact that the proposed method of producing a medicinal product provides a high therapeutic effect in the treatment of severe forms of septic and autoimmune diseases through the reduction of inflammatory processes in tissues and reduce recovery time in 2-3 times in comparison with the known method and can be successfully used for the treatment of severe forms of septic and autoimmune diseases.

Example

Prepare two batches of medication with gelatinosum (the prototype) and gelofuzina. The product is a lyophilized powder in penicillin vials for preparation of solution for injection, representing the peptide fraction isolated from tissues or cells of the spleen mammals by grinding the tissue of the spleen, extraction and ultrafiltration extract using a filter with a pore size of 45,000 daltons (0.1 microns). The drug is composed of peptides spleen, gentamicin sulfate, auxiliary substance that prevents coagulation of protein molecules - relational (first party), and gelofusine (second party) in a certain ratio (see table 2)

Table 2
The drug, made from the spleen (dry substance in penicillin vials)
1 batch of medication2 party drug
the peptides of the spleen16±1.6 mg (protein)the peptides of the spleen16±1.6 mg (protein)
relational94±9,MHgelofusine94±9,MH
gentamicin sulfate0,35±0,MHgentamicin sulfate0,35±0,MH

From each batch, take three bottles. In each vial is injected at 4 ml of 0.9% sodium chloride solution. Dissolve for 10 minutes, occasionally gently stirring, avoiding strong foaming. Then the solution from the vials are transferred into sterile sectionone flat-bottomed tablets designed for culturing cells (such Costar® 3506 or similar). Allow the solution to stand for 30 minutes. Next, looking at the sediment using inverted mikros the OPA at magnification ×400. Microscopic examination of the sediment in the drug gelatinosum the number of particles in the field of view 215±50 particle size of 0.5 to 9 μm, which form clusters, in the form of bunches with a few pieces of particles up to several tens of pieces. Microscopic examination of the sediment in the drug gelofuzina the number of particles in the field of view 34±18, particle size of 0.3-1 μm. Clusters of particles are observed in each field of view, the number of clusters does not exceed 4-5.

Thus, the analysis of sediment samples of the drug demonstrates the significant benefits of using gelofuzina as auxiliary substances for preventing coagulation of protein molecules.

Pathogenetic rationale for the use of the drug for the treatment of patients with secondary immunodeficiencies

During the development of the drug, we have taken into account previously set data of domestic and foreign researchers.

The spleen has more power capture of microorganisms per unit mass compared with the liver and is the dominant area of removal from the bloodstream pneumococcal infection (Schulkind et al., 1967). In connection with intensive organ perfusion (up to 4% of circulating blood volume per minute) macrophages of the spleen provides up to 15% of the total clearance of antigenic particles, bacteria and other pathogens (Lynch, Kapila, 1996).

The spleen contains 25% reticuloendothelial just the PR is of anima, 30% of its volume is lymphoid tissue, it is the main organ for the production of antibodies (Fontain L.N., 1967; Yakimenko LB, Uman A.A., 1972; Bart P., 1976). The major manifestations of the protective functions of the spleen are: filtering the blood (Corazza et al., 1990), phagocytic activity, participation in the primary immune response, the development of specific antibodies and non-specific immunoglobulins, the formation of biologically active substances, affecting different parts of the immune homeostasis (F. C. Tischendorf, 1988).

The spleen is the major site of production of lymphocytes and faguoqitirute mononuclear cells. It contains 25% of T - and 60% of b-lymphocytes from the total pool of lymphocytes in the body. The number of antibodies produced by the lymphoid system of the spleen was significantly higher than their synthesis in other lymphoid organs (Staniza A., 1988; Yosafet N. et.al., 1989).

It is important also, and this function of the spleen, as products captina, properdin, and fibronectin. These non-specific opsonins, produced mostly in the spleen (Lockwood, 1983), provide non-specific (primarily antimicrobial) resistance of the organism.

Stromal cells of the spleen are the producers of the growth factor hepatocyte or scattering factor (HGF/SF - hepatocyte growth factor / scatter factor) (Kono et al., 1992; Matsumoto, Nakamura,1992; Skibinski et al., 2001). This peptide is Park the other regulator of mesenchymal-epithelial interactions, stimulates the growth and motility of epithelial cells (Takahashi et al., 1993; Yamada et al., 1994; Kermorgant et al., 1997; Weimar et al., 1998; Wormstone et al., 2000). In addition, the spleen is involved in the synthesis of insulin-like growth factors (IGF-I and-II insulin-like growth factor I and II) (Hoeflich et al., 2001), although the main source is the liver (Lee et al., 2001), as well as specific splenic-derived growth factor (SDGF-spleen-derived growth factor) (Suzuki et al., 1988). All of these cytokines have a strong mitogenic effect on hepatocytes (Kato et al., 1997; Sato et al., 1997; Gao et al., 2001; and others), therefore, stimulate liver regeneration (Galimi et al., 2001).

The mechanism of drug action

The mechanism of action of the drug is associated with the presence of cytokines, polypeptide mediators that are involved in the formation and regulation of protective reactions of an organism.

In the drug identified the following key cytokines:

1. Proinflammatory cytokines: IL1β, TNFα, IL6.

2. Anti-inflammatory cytokines: IL1-RA, IL10, IL4.

3. Chemoattractant: IL8.

4. Regulatory cytokines: IL4, IL2.

5. Growth factors: G-CSF, TGFβ.

6. Interferons: interferon-α (IFNα), interferon-γ (IFNγ).

To determine the range of key cytokines and quantity of their content in the product is used the method of "sandwich" - variant enzyme-linked immunosorbent assay using enzyme immunoassay systems for the determination of cytokines man is ka (LLC "Cytokine"-IB.) (see table 3).

Table 3
The quantitative content of the key cytokines in the product (PG/ml).
CytokinesThe concentration of cytokines Me (min-max)Donors (serum PG/ml)Biological effects and biological target
I. Pro-Inflammatory cytokines.
Interleukin 1β (IL1β)67 (48-87)23-37The most sensitive marker of inflammation, mediates observerfelicia reactions: fever, leukocytosis, synthesis AFB, increases vascular permeability.
Interleukin 6 (IL6)95 (80-124)26-32The action is similar to that IL1β. A Central role in the acute phase of the immune response and the adjustment of the balance of Pro - and anti-inflammatory cytokines
The tumor necrosis factor (TNFα)42 (36-49)26-41Key in the process of inflammation. Cytotoxic is some activity against tumors and infected cells
II. Anti-inflammatory cytokines.
Receptor antagonist IL1β-(IL1RA)205 (196-215)200Blocks receptors for 1β.
Interleukin 10 (IL10)120 (70-170)50Suppressor factor for cellular and humoral immunity, stimulating the secretion of Ig (IgM to IgA). Potentiates the anti-inflammatory effect, reducing the synthesis of proinflammatory cytokines, chemokines.
IL4 - see regulatory cytokines
III. Chemoattractant.
Interleukin 8 (IL8)79 (63-144)29-58Provides migration of monocytes, lymphocytes, neutrophils into the inflammatory focus.
IV. Regulatory cytokines.
Interleukin 4 (IL4)35 (45-65)19-28 Factor activation and differentiation of B-LF., bone marrow precursors and fat cells. It stimulates the production of IgE.
Interleukin 2 (IL2)2,3 (1,8-2,8)2,1-4,5Generates cytotoxic T-LF. Stimulates growth and differentiation of T-LF. on Th1-type immune response.
V. growth Factors.
Granulocyte colonialismo-regulating factor (G-CSF)75 (57-91)50The factor of activation and differentiation of bone marrow precursors of monocytes and neutrophils.
Transforming growth factor (TGF (3)120 (70-170)27-60Transfer of intracellular regulatory signals. Regulation processes proliferate, differentiation, migration and apoptosis.
VI. Interferons.
Interferon α(IFNct)54 (22-56)Has the most pronounced and tivirus and antiproliferative action.
Interferon γ(IFNγ)60 (41-79)16-32Regulation cooperation of cells in the immune response. The maturation and differentiation of T-LF. in the thymus. Coordinates the interaction between T-LF. and neutrophils.
Notes: Me - median, min-max - dispersion concentrations of cytokines in different batches of the drug.

As you know, cytokines primarily regulate the development of local defence reactions in the tissues with the participation of various types of blood cells. They also induce the activation of the endothelium, leading to increased vascular permeability, increased expression of adhesion molecules and increased procoagulant activity by histamine, prostaglandins and other mediating the development of inflammatory reactions. Chemokines, in turn, increase the directional migration of neutrophils and lymphocytes in inflammation, activate phagocytosis and production of reactive oxygen species, mediating anti-infective effect. At the same time Pro-inflammatory cytokines activate the metabolism of the connective tissue, stimulates the proliferation of fibroblasts and epithelial cells, providing the regenerative processes in the damaged tissues.

The influence of cytokines in the hematopoietic the entrances associated with significant activation of hematopoiesis, manifested by increased numbers of leukocytes, lymphocytes and cytotoxic subsets, natural killer cells and replenish losses of neutrophils in the home purulent inflammation.

Within the immune system cytokines realize the relationship between non-specific defensive reactions and specific immunity in both directions. Great importance is attached to the morphogenetic function of the immune system and its responsibility for the regulation of organ regeneration, for the processes of adaptation and compensation. The decrease of the total population of lymphocytes and their subpopulations, as well as the imbalance of regulatory mediators of immunity is a predisposing factor for the formation of organ dysfunction, as it is T-LF. are the main effector transmission repair information cells parenchymatous bodies.

Under the action of the drug is undergoing profound changes in the immune effectors. Due to stimulation of hematopoiesis their number increases, an increasing number of differentiated subpopulations, stimulated their functional activity. First of all these processes occur in the immunoregulatory system T-lymphocytes, predominantly of the Th1 subpopulation.

The drug complex of cytokines of the first phase of the immune response capable of modulating the activity of immune effector is in this phase (macrophages, Th1 lymphocytes and neutrophilic granulocytes).

In cases involving the development of secondary immunodeficiency cellular link and macrophage system, there is an imbalance of cytokine status, requiring an immune immunomodulators cytokine nature. Depending on the nature of the imbalance in the first place, the ratio of Pro - and anti-inflammatory cytokines and mediators mediating Th1 (cellular) and Th2 (humoral) type immune response, cytokinemia should be aimed at enhancing the actions of endogenous cytokine mediators, by introducing into the body by natural and recombinant cytokine drugs or substitution therapy (for the oppression of their products). If hyperproductive cytokines, leading to the development of the systemic inflammatory response and septic shock should be anticytokine therapy to reduce their products using specific inhibitors of cytokines and their products, including drugs anti-inflammatory cytokines.

Studies have confirmed that a wide range and the optimum concentration of cytokines in the drug complies with the principles of citicentre.

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The method of obtaining drug immunomodulator for the treatment of severe forms of septic and autoimmune diseases, comprising mixing the biologically active substance is a peptide fraction isolated from tissues or cells of the spleen mammals, with a substance that prevents coagulation of protein molecules, and an antibiotic, wherein as a substance that prevents coagulation of protein molecules, use GE is Opuzen.



 

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3 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutical engineering, and concerns a combined antituberculous remedy containing isonicotinic acid hydrazide (isoniaside) and 2-benzylbenzimidazole (dibazol), and a polymer carrier that is an interpolymer complex of poly(meth)acrylic acid and polyethylene glycol, as well as a method for preparing it.

EFFECT: antituberculous remedy according to the invention has bacteriostatic and bactericidal action on tuberculosis mycobacteria; it provides the continuous maintainance of the active substance concentration at the therapeutically effective level; it causes no considerable blood variations; it is 2,5 times less toxic than isoniaside, and 10 times more active than isoniaside.

7 cl, 1 dwg, 11 tbl, 16 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine. An antiviral agent is used by individuals having sensitive face skin, inactivates viruses, such as norovirus and influenza virus, and has the excellent bactericidal properties. The antiviral agent wherein the percentage of total laurate soap and myristate soap makes 70 wt % or more at total soaps with saturated fatty acids, and the percentage of stearate soap and the percentage of palmitate soap makes less than 15 wt % at total soaps with saturated fatty acids, and the percentage of oleate soap making 50 to 75 wt % of total soaps. The group of inventions disclosed a detergent causing no environmental pollution, as it is easily degraded in the natural environment.

EFFECT: group of inventions provides inactivating the virus with the very low concentration of the agent, causes no eczema and allergic dermatitis.

5 cl, 3 tbl, 15 dwg, 11 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine. An antiviral agent is used by individuals having sensitive face skin, inactivates viruses, such as norovirus and influenza virus, and has the excellent bactericidal properties. The antiviral agent wherein the percentage of total laurate soap and myristate soap makes 70 wt % or more at total soaps with saturated fatty acids, and the percentage of stearate soap and the percentage of palmitate soap makes less than 15 wt % at total soaps with saturated fatty acids, and the percentage of oleate soap making 50 to 75 wt % of total soaps. The group of inventions disclosed a detergent causing no environmental pollution, as it is easily degraded in the natural environment.

EFFECT: group of inventions provides inactivating the virus with the very low concentration of the agent, causes no eczema and allergic dermatitis.

5 cl, 3 tbl, 15 dwg, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents a method for increasing: biocidal and therapeutic action of a suspension-cream with enrofloxacin consisting in detoxification and polymerisation of 250-300 mg/ml of enrofloxacin at first with 0.15±0.05% glutaric aldehyde with 0.15±0.05% alkyldimethylbenzyl ammonium chloride at 38-40°C for 2-3 days, and then 1-2% aethonium or 0.5% Biopag-D at 38-40°C for 2-3 days, further added to melted Vaseline (80%) vegetable oil (10%), and 0.1% dimethyl sulphoxide at 10-15 mg of the preparation per 1 ml of normal saline with a flavour for suspending.

EFFECT: invention provides higher biocidal activity of enrofloxacin on pathogenic bacteria, viruses and mould fungi, and regenerative action on tissues.

5 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention refers to veterinary science. The method of treating mastitis in non-lactating cows involves administering an antimicrobial preparation presented by apramycin in a combination with xanthane gum in ratios, wt %: apramycin - 5.0-10.0; xanthane gum - 0.25-1.0; distilled water - up to 100 with the preparation introduced intracisternally after the last evening milking before going non-lactating in the amount of 10 ml in a single dose.

EFFECT: invention provides the higher clinical effectiveness and reduced material expenses.

1 tbl, 1 ex

Nanoemulsion // 2491917

FIELD: medicine.

SUBSTANCE: group of inventions refers to a nanoemulsion for active agent delivery, a method for preparing it, compositions containing it, and to using a nanoemulsion for preparing pharmaceutical compositions for local application and cosmetic compositions for skin application. The declared nanoemulstion contains a water ingredient and a carrier which contains a lipophilic ingredient in the amount of 0.1-15 wt %, a surfactant and isopropyl and/or 1-propyl alcohol. The average emulsified particle diameter makes less than 100 nm. The method for preparing the nanoemulsion involves mixing the water ingredient and carrier containing the lipophilic ingredient, surfactant and isopropyl and/or 1-propyl alcohol, for preparing the nanoemulsion at temperature 50-60°C. The invention also refers to the composition for photodynamic therapy containing the above nanoemulsion and the active agent representing 5-aminolevulinic acid, a derivative, a precursor and/or a metabolite thereof. The above composition is applied to prepare the drug substance for photodynamic therapy and to treat senile keratosis. What is also declared is a diagnostic composition for detecting the dividing cells which contains the nanoemulsion and 5-aminolevulinic acid. The invention also refers to a kit for photodynamic therapy which comprises the composition for photodynamic therapy and one ingredient specified in a photoresist coating, an agent for attaching the above coating or an agent for applying the composition.

EFFECT: invention provides better stability and intensified cell and tissue penetration of the nanoemulsion.

25 cl, 6 dwg, 9 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to vaccinology and cell biology.

EFFECT: what is presented is a method for preparing the cytomegalovirus vaccine ensured by specifying a cell type wherein this virus replicates; the vaccine and method for immunising an individual against CMV.

19 cl, 6 dwg, 5 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to hygiene and may be used for skin preparation for protection against infection, for foot skin and footwear disinfection for mycosis prevention. The formulation contains poly-(4,9-dioxaadodecane guanidine) chloride, phosphate or succinate, methylisothiazolinone, sorbitol, zinc acetate, dish mustard extract and water.

EFFECT: invention provides higher biocidal activity of the formulation, reduced toxicity and improved application properties.

2 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention refers to veterinary science. Using ORF-2 PCV-2 protein for preparing an immunogenic composition applicable for relieving concurrent infections caused by one or more viral (e.g. PRRS), bacterial and/or fungal pathogens (e.g. Actinobacillus pleuropneumoniae, Haemophilus parasuis, Mycoplasma hyrhinis, Mycoplasma hyopneumoniae, Pasteurella multocida, Salmonella spp., or Strepococcus suis) different from PCV2 in pigs or pig herds with a percent of the concurrent infections in relation to one or more infections are reduced by more than 10% as compared to an unvaccinated reference group.

EFFECT: relieving the concurrent infections caused by one or more viral (eg PRRS), bacterial and/or fungal pathogens.

8 cl, 2 tbl, 1 ex, 11 dwg

FIELD: medicine.

SUBSTANCE: invention refers to veterinary science. Using ORF-2 PCV-2 protein for preparing an immunogenic composition applicable for relieving concurrent infections caused by one or more viral (e.g. PRRS), bacterial and/or fungal pathogens (e.g. Actinobacillus pleuropneumoniae, Haemophilus parasuis, Mycoplasma hyrhinis, Mycoplasma hyopneumoniae, Pasteurella multocida, Salmonella spp., or Strepococcus suis) different from PCV2 in pigs or pig herds with a percent of the concurrent infections in relation to one or more infections are reduced by more than 10% as compared to an unvaccinated reference group.

EFFECT: relieving the concurrent infections caused by one or more viral (eg PRRS), bacterial and/or fungal pathogens.

8 cl, 2 tbl, 1 ex, 11 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to pharmacology and concerns using hydrophobin polypeptides as an active penetration intensifier in cosmetic and/or pharmaceutical compositions. What is also declared is a method for preparing an agent containing hydrophobin and the active substance.

EFFECT: group of inventions provides stronger active skin penetration.

11 cl, 3 ex, 1 tbl, 2 dwg

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