An object of the invention is a membrane- forming pharmaceutical composition. The invention has applications in pharmacy and veterinary medicine.

To date, commercially available dressings are manufactured based on various technologies and have very specific and personalized properties. The most important types of such medical devices include :

Despite the variety indicated, there are no available forms characterized by a change in the mounding state after application. The idea underlying the design of such type of adhesive dressings is based on the development of a form which is convenient and easy to apply even to inaccessible body surfaces, which is characteristic of liquid systems, with the possibility of retaining it at the site of application for a sufficiently long time, which is the advantage of solid forms. The so-called liquid dressings are included in this category, and the membrane-forming pharmaceutical composition developed by the authors of the present invention can be considered to be in this category. Currently available dressings of such type are prepared on the basis of hydrophilic polymers whose task is to increase the absorbent properties of the preparation. However, under the influence of moisture, body fluids (e.g. : blood, serous exudates) they usually lose their adhesive properties (adhesion to the wound) or increase their volume, and after saturation they require changing. Therefore, there is still a search for film-forming compositions devoid of the above-mentioned drawbacks, capable of immediately forming a protective coating on the skin or mucous membranes against harmful external influences such as mechanical contaminants or moisture, stopping bleeding from broken skin layers and separating the injured area from the environment with a waterproof barrier preventing accidental bacterial infection, and compositions containing it. Unexpectedly, the described problems were solved by the presented invention.

A first subject of the invention is a membrane -forming pharmaceutical composition for forming a tight elastic coating on the skin or mucous membranes characterized in that it contains cellulose ethyl ether in an amount of from 2% to 15% by weight of the composition, ethyl alcohol in an amount of from 5% to 93% by weight of the composition, and an organic chemical compound from the group of alkyl halides, advantageously dichloromethane in an amount of from 5% to 93% by weight of the composition, and excipients. Equally advantageously, the composition according to the invention comprises excipients selected from the group consisting of plasticizers, colorants, co-solvents, colorants, stabilizers. In a further advantageous implementation of the invention, as plasticizers the composition comprises a mixture of paraffinic hydrocarbons, advantageously petroleum jelly in an amount of from 0.5% to 20% of the composition and/or an organic chemical compound from the group consisting of monounsaturated fatty acids of the omega-9 type, advantageously oleic acid in an amount of from 1% to 10% by weight of the composition. In a further advantageous implementation of the invention, the composition comprises as a colorant an organic chemical compound in the form of a 1,4-thiazine derivative, advantageously methylene blue in an amount of from 0.01% to 1.5% by weight of the composition. In a further advantageous implementation of the invention, the composition comprises as co-solvent a methyl ketone, advantageously acetone in an amount of 1% to 30% by weight of the composition. Preferably, the composition according to the invention contains as a stabilizer an inorganic chemical compound, advantageously zinc oxide in an amount of 0.5% to 10% by weight of the composition.

A second object of the invention is an application of the composition defined in the first object of the invention as a membrane-forming, fast-drying medical material with insulating, protective properties for protecting skin and mucous membranes from infection and/or for stopping bleeding in humans and animals .

A third object of the invention is the use of the composition defined in the first object of the invention for preventing bacterial infection of the teats of cows during the drying period, advantageously as a lipogel liquid with increased viscosity, having membrane-forming properties. When applied in contact with naturally moist skin, it forms, within a few minutes, a tightly adherent, teat-like, elastic film that persists at the site of application for a period of about a week, providing a physical protective barrier to prevent accidental bacterial infection of the teats of drying cows.

A fourth object of the invention is the use of the composition defined in the first object of the invention for preventing infection of a healthy mammary gland during the drying period. The proposed membrane-forming pharmaceutical composition based on the use of properties of polymer of natural origin Etylocellulose provides a possibility to prepare a dressing which is liquid at the moment of application, and under the influence of moisture in the air, natural moisture of the skin or blood oozing from an open wound, forms a tightly adhering layer to the body, which does not expand and remains insoluble in the presence of body fluids (blood, sweat, mucus) . The rate of formation of the insulating film at the site of application of the dressing made based on the film-forming pharmaceutical composition is directly proportional to the degree of humidity of the surface to which it is applied. In a situation where the surface is completely wet, the polymeric film forms immediately. The liquid membrane- forming pharmaceutical composition, due to the lipophilic nature of the fi lm produced, does not have absorbent properties . However, it is an optimal choice in all those situations where there is a need for immediate formation of a protective film on the skin or mucous membranes , stopping bleeding from interrupted s kin layers and separating the inj ured area from the environment with a waterproof barrier preventing accidental bacterial infection . It al so appears to be optimal for application to moist mucous membranes such as the mouth or, for example , the inside of the teat of a cow ' s udder .

The present invention relates to the qualitative and quantitative composition and technology for the production on a laboratory scale of semi -solid, barrier systems changing their cons istency after application to the s kin and mucous membranes , prepared on the basis of a polymer of natural origin . It can be used directly as a ready-to-use form of medical material , carri er of therapeutic substances of lipophilic character, with insulating properties , protecting against harmful inf luence of external factors (mechanical contamination, moisture ) to protect skin layers and mucous membranes against infection or to stop bleeding in humans and animals .

The semi-liquid composition is made of a polymeric membrane forming substance ethyl cellulose .

Main ingredients used in the invention:

Ethyl cellulose:

Synonyms: Ethylcellulosum (monograph FP XI, vol. II, pp . 2801- 2802, Ph. Eur.) , Ethylcellulose (USPNF) , Aquacoat ECD, Aquaion, E462, Ethocel, Surelease, Cellulose ethyl ether [9004-57-3] (CAS) .

Chemical Structure: Ethyl cellulose is a polymer of natural origin, a derivative of cellulose - it is the ethyl ether of cellulose. It is a long-chain polymer of p-units of anhydroglucose linked by acetal bonds:

The physicochemical properties of ethyl cellulose depend on the polymer chain length (n value) and the degree of ethoxyl substitution (DS=1,2,3) . Based on the degree of ethoxyl substitution, there are two types of polymers available on the market: Standard - with degree of ethoxyl substitution DSC ( 48.0% , 49.5% ) , and Medium - with degree of ethoxyl substitution DSC ( 45.0%, 47.0%) .

Preparation: Ethyl cellulose is produced by reacting purified cellulose derived from wood pulp with sodium hydroxide solution NaOH, followed by ethylation of the resulting alkaline cellulose with chloroethane as shown below: .R-ONa + C2H5CI R-OC2H5 + NaCl

Where R represents the cellulose radical. Appearance: White or yellowish-white powder, or granular powder (according to FP XI) . It is odorless, tasteless, and has no caloric content.

Solubility: Ethylcellulose is practically insoluble in glycerol, propylene glycol, and water. Ethyl cellulose containing less than 46.5% ethoxyl groups (DS<46.5%) is readily soluble in chloroform, methyl acetate, and tetrahydrofuran and in aromatic hydrocarbon mixtures with ethanol (96%) . Ethyl cellulose, which contains not less than 46.5% ethoxyl groups (DSh46.5%) , is readily soluble in chloroform, ethanol (96%) , ethyl acetate, methanol and toluene.

Stability: Ethyl cellulose is a stable, slightly hygroscopic material. It is resistant to alkalis, both dilute and concentrated, and to salt solutions. Ethylcellulose is subject to oxidative degradation in the presence of sunlight or UV light at elevated temperatures. This can be prevented by using antioxidants and chemical additives that absorb light in the 230-340 nm range. Ethyl cellulose should be stored at a temperature not exceeding 32 °C, in a dry place, away from all heat sources. It should not be stored near peroxides or other oxidizing agents. It is microbiologically stable - no mold or rot .

Viscosity: The viscosity of ethyl cellulose solution increases with increasing ethyl cellulose concentration and polymer chain length .

Toxicology: Ethyl cellulose is a non-toxic substance widely used in oral pharmaceutical preparations as well as in food products. Ethylcellulose is not metabolized after oral ingestion and is therefore a non-caloric substance. Because it is not metabolized, it is not recommended as an excipient for parenteral products; its parenteral use may be harmful to the kidneys. Application in pharmaceutical industry: Ethyl cellulose is widely used in oral and topically applied drug formulation technology. The main use of ethyl cellulose in oral formulations is as a hydrophobic coating agent for tablets and granules. Ethyl cellulose coatings can be used to modify the release of drug substances from the drug formulation, to mask unpleasant taste or to improve stability. It can be used in controlled release matrix tablet manufacturing technology. Ethyl cellulose dissolved in an organic solvent or solvent mixture can be used alone to produce water insoluble films. An aqueous polymeric dispersion (or latex) of ethylcellulose such as Aquacoat ECD or Surelease can be used to produce ethylcellulose films without the need for organic solvents. The mechanism for controlling the release of drug substances through ethylcellulose coated forms is based on diffusion. This is usually a slow process unless the drug form has a large release surface area (e.g. pellets or granules compared to tablets) . High viscosity ethyl cellulose species are used in microencapsulation. Drug release from an ethyl cellulose microcapsule is a function of microcapsule wall thickness and surface area. It is sometimes used as a binder in tablet manufacturing technology. Tablets made with it are hard, have long disintegration time and significant abrasion resistance. It has been tested as an emulsion stabilizer. Ethyl cellulose is also sometimes used in dental drugs as a release control agent. In cosmetics it is used as a thickening agent in creams, lotions or gels. Ethyl cellulose is a popular additive in food products.

Ethanol :

Synonyms: Ethanolum (96 Per Centum) (FP monograph XI, vol. II, pp . 2792-2794, Ph. Eur . ) , Ethanol 96% (V/V) , Alcohol, Ethyl alcohol, Ethanol [64-17-5] (CAS) . Aqueous solutions of ethanol up to 40% (V/V) are referred to as Ethanol Solutions, and those greater than 40% (V/V) are referred to as Medicinal Spirits. Definition: contains ethanol C2H5OH; m.cz. 46.07; 95.1% (V/V) (92.6% m/m) to 96.9% (V/V) (95.2% m/m) at 20°C, calculated from relative density using alcoholometric tables, and water. Appearance: Colorless, transparent, volatile, flammable and hygroscopic liquid. Boiling point is approximately 78°C. Solubility: Ethanol is miscible with chloroform, ether, glycerin and water. Mixtures with water show the property of contraction (decrease in volume) and in concentrations of 95%-96% form an azeotropic mixture.

Stability: Aqueous solutions of ethanol can be sterilized by autoclaving or filtration and should be stored in airtight containers in a cool place.

Toxicology: Ethanol is rapidly absorbed from the gastrointestinal tract and its vapors can be absorbed through the lungs. It is metabolized, primarily in the liver, to acetaldehyde, which is then oxidized to acetate. Ethanol is a central nervous system depressant. In concentrations of 5%-10% (V/V) , it is sometimes a component of parenteral administration products. Subcutaneous injection of 96% (V/V) ethanol causes considerable pain and subsequent anesthesia. If injections are made close to nerves, nerve inflammation and degeneration may occur. This effect is used therapeutically to induce anesthesia in cases of severe pain, although the practice of using alcohol in nerve blocks is controversial. Alcohol may cause skin irritation when applied topically.

Application in pharmaceutical industry: Ethanol and aqueous solutions of ethanol at various concentrations are widely used in pharmaceutical preparations and cosmetics. Although it is mainly used as a solvent, it is also sometimes used as an antimicrobial and preservative. Topically administered ethanol solutions act as absorption promoters and disinfectants.

Dichloromethane :

Synonyms: OD methylene chloride (OD monograph FP XI, vol. I, p. 655) , Methylene chloride [75-09-2] (CAS) .

Form and Properties: An organic compound of the alkyl halogen group, a chlorine derivative of methane with the formula CH2C12 (m.w. 84.9) . Colorless liquid, quite insoluble in water, miscible with ethanol 96% (V/V) . It is a volatile compound with a boiling point of 39°C-42°C.

Toxicology: Toxicity results from high volatility. Inhalation of its vapors in significant concentrations and with prolonged exposure may cause nausea and vomiting. Possible eye irritation, possible mutagenic effects.

Use in pharmaceutical industry: Used as solvents and co-solvent for lipophilic compounds, process solvent for water insoluble cellulose derivatives. When used as co-solvent, it lowers the evaporation temperature of other solvents. Heat transfer fluid. Often used in pharmaceuticals because it is the least toxic of the chlorinated hydrocarbon derivatives.

Excipients : Plastif iers :

Vaseline - smeary, odorless, low-melting, non-drying, white through yellow to brown in color - in all cases quite translucent. It is a mixture of paraffin hydrocarbons (alkanes) from the borderline of the solid and liquid states of aggregation in normal ambient conditions (melting point 35-45 °C) - mainly docosane (C22H46) and tricosane (C23H48) . Other versions may have a higher melting point (36-60 °C) and contain mainly saturated hydrocarbons with >25 carbon atoms. It is obtained from selected types of crude oil. An anhydrous pharmaceutical ointment base.

Oleic acid (Latin: acidum oleicum, from oleum - oil) - an organic chemical compound from the group of monounsaturated fatty acids of omega-9 type. It is a cis-isomer of elaidic acid. This acid occurs naturally in fats (it is the main component of olive oil and fish oil) , from which it is extracted.

Co-solvent :

Acetone - propanone, methyl ketone - an organic chemical compound in the ketone group, the simplest aliphatic ketone. It has a pungent, characteristic odor. It mixes in any proportion with water, ethanol, ethers and other low molecular weight ketones. Acetone is a commonly used organic solvent with high polarity. It dissolves most soft plastics, varnishes, fats, oils. It is used in the manufacture of drugs, dyes, paints, varnishes, and cleaners. Acetone is produced efficiently by the bacteria Clostridium acetobutylicum, it is currently obtained on an industrial scale by the cumene method from propylene and also catalytically from isopropyl alcohol, acetylene by butanolacetone fermentation.

Pigment :

Methylene Blue - At room temperature it is an odorless, dark green powder, with water it gives a blue solution. Bulk density 400-600 kg/m ³ . Used as a pH indicator. It turns green in strongly acidic solutions and blue to dark blue in slightly acidic, neutral and basic solutions. It is also used as a dye in biology and has many applications in medicine. It is used as a diagnostic and antimicrobial agent as well as in cyanide and carbon monoxide poisoning .

Stabilizer:

Zinc oxide - (zinc white) , ZnO - a chemical compound from the oxide group, a combination of oxygen and zinc in the second oxidation state. This compound is obtained by roasting zinc ore: zinc sulphide (ZnS) or zinc carbonate (ZnCO3) in the presence of air. It is used as an additive to paints and varnishes, in cosmetics and ceramics and as a filler and stabilizer for rubber, rubber and plastics, for the production of insulating masses, backfills. Zinc oxide has a slight antibacterial effect and accelerates wound healing. For this reason, it is used as an ingredient in ointments and salves to treat skin diseases. It is also used in dentistry for temporary fillings.

The present invention is designed to overcome the drawbacks of the state of the art and to provide a composition with a broader spectrum of indications for prolonged maintenance of a polymeric, flexible, tight, tightly adherent coating for skin coatings, produced by a change in consistency from liquid to semi-solid, under the influence of body temperature and contact with body fluids or secretions (e.g. : sweat, blood, serous fluid, milk) . In this regard, the invention provides a pharmaceutical composition which, when applied at the point of use, leads to the effect of producing a coating with insulating properties against harmful external influences (mechanical contaminants, moisture) for protecting skin coatings and mucous membranes against infection or for stopping bleeding in humans and animals. The developers have found that the composition is effective in inducing topical protection of the skin and mucous membranes, which persists for a specific duration of application depending on the composition.

Example 1

A membrane- forming pharmaceutical protective composition comprising dichloromethane, ethyl alcohol and cellulose ethyl ether .

A method of making a membrane- forming pharmaceutical composition comprised dissolving and mixing the ingredients. 2.0 g of cellulose ethyl ether was conjugated with 93.0 g of dichloromethane. To the resulting mixture, 5 g of ethanol was added. Then the pharmaceutical composition was conditioned at the temperature from 2°C to 8°C for 24 hours until a colorless liquid of uniform consistency and characteristic smell was produced .

The prepared formulation containing 2% cellulose ethyl ether was subjected to examination of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation . The samples were evaluated continuous ly from the time of application for the first 30 min . then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h . Commercially available polymer formulations were used as reference During the study, it was shown that the average time to form a tight , flexible coating was 3 sec . which was 35 faster than the market formulation . The coating retention length was 120 h and was 24 h longer than the market formulation .

Example 2

A membrane- forming pharmaceutical protective composition comprising dichloromethane , ethyl alcohol and cellulose ethyl ether .

The method o f making the membrane- forming pharmaceutical composition was to dissolve and mix the ingredients . 93 g of dichloromethane was mixed with 5 g of ethanol . To the produced mixture, 2 . 0 g of cellulose ethyl ether was added and beakered . The pharmaceutical composition was then stirred at 20°C to 25°C for 3 min at 600 rpm to produce a colorless l iquid of uni form cons istency and characteristic odor .

The formulation so prepared containing 2 % cellulose ethyl ether was subj ected to examination of the rate o f formation of an elastic polymeric film on the hydrophil ic fluid and the length of persistence of this film on the skin surface of experimental animals . The study was conducted for 8 days on 12 teats of three experimental animals ( cows ) . The study consi sted of measuring the coating retention time and visual evaluation . The samples were evaluated continuous ly from the time of application for the first 30 min . then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h . Commercially available polymer formulations were used as reference During the study, it was shown that the average time to form a tight, flexible coating was 3 sec. which was 35 faster than the market formulation. The coating retention length was 120 h and was 24 h longer than the market formulation.

Example 3

A membrane- forming pharmaceutical protective composition comprising dichloromethane, ethyl alcohol and cellulose ethyl ether .

The method of making the membrane-forming pharmaceutical composition was to dissolve and mix the ingredients. 93 g of ethanol was mixed with 5 g of dichloromethane. To the produced mixture, 2.0 g of cellulose ethyl ether was added and beakered. The pharmaceutical composition was then stirred at 20°C to 25°C for 10 min at 600 rpm to produce a colorless liquid of uniform consistency and characteristic odor.

The formulation so prepared containing 2% cellulose ethyl ether was subjected to examination of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h. Commercially available polymer formulations were used as reference During the test, it was shown that the average time to form a tight, flexible coating was 29 sec. which was 11 sec. faster than the market formulation. The film retention time was 96 h and was equal to that of the market formulation .

Example 4. A membrane- forming pharmaceutical protective composition comprising dichloromethane , ethyl alcohol and cellulose ethyl ether .

The method of making a membrane - forming pharmaceutical composition was to dissolve and mix the ingredients . 80 g of dichloromethane was mixed with 5 g of ethanol . To the produced mixture, 15 . 0 g of cellulose ethyl ether was added and beakered . The pharmaceutical composition was then stirred at 20 °C to 25°C for 25 min at 600 rpm to produce a colorless liquid of uni form cons istency and characteristic odor .

The formulation prepared in thi s way containing cel lulose ethyl ether at 15% concentration was subj ected to examination of the rate o f formation of an elastic polymeric film on the hydrophilic fluid and the length o f persistence of this film on the skin surface of experimental animals . The study was conducted for 8 days on 12 teats of three experimental animals ( cows ) . The study cons isted of measuring the coating retention time and visual evaluation . The samples were evaluated continuously from the time of application for the first 30 min . then at interval s of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h . Commercially available polymer formulations were used as a reference During the study, it was shown that the average time to form a tight , flexible coating was 5 sec, which was 33 sec faster than the market formulation . The coating retention time was 144 h, 48 h longer than the market formulation .

Example 5

A membrane- forming pharmaceutical protective composition comprising dichloromethane , ethyl alcohol and cellulose ethyl ether . The method of making a membrane -forming pharmaceutical composition was to dissolve and mix the ingredients. 80 g of ethyl alcohol was mixed with 5 g of dichloromethane. To the produced mixture, 15.0 g of cellulose ethyl ether was added and beakered. The pharmaceutical composition was then stirred at 20°C to 25°C for 30 min at 600 rpm to produce a colorless liquid of uniform consistency and characteristic odor.

The formulation prepared in this way containing cellulose ethyl ether at 15% concentration was subjected to examination of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h. Commercially available polymer formulations were used as a reference During the test, it was shown that the average time to form a tight, flexible coating was 30 sec, which was on average 3 sec faster than the market formulation. The coating retention time was 96 h and was about equal to that of the market formulation .

Example 6

A membrane- forming pharmaceutical protective composition comprising dichloromethane, ethyl alcohol and cellulose ethyl ether, and the excipients oleic acid and methylene blue.

The method of making the membrane-forming pharmaceutical composition was to dissolve and mix the ingredients. 91.99 g of dichloromethane was mixed with 5 g of ethanol. To the produced mixture, 0.01 g of methylene blue was added and beakered. The mixture was then stirred at 20oC to 25oC for 3.5 min at 570 rpm to produce a blue liquid of uniform consistency and characteristic odor. To the obtained solution of non-aqueous methylene blue, 1 g of oleic acid was introduced and stirred at room temperature for 1 min and 15 sec. at 620 rpm. To the resulting mixture, 2 g of cellulose ethyl ether was introduced and stirred at room temperature for 4 min at 800 rpm until a colored (blue) liquid of uniform consistency and characteristic odor was obtained.

The formulation thus made containing 2% cellulose ethyl ether was subjected to a study of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h. Commercially available polymer formulations were used as reference During the test, it was shown that the average time to form a tight, flexible coating was 8 sec. which was 30 faster than the market formulation. The coating retention length was 168 h, which was 96 h longer than the market formulation .

Example 7

A membrane- forming pharmaceutical protective composition comprising dichloromethane, ethyl alcohol and cellulose ethyl ether, and the excipients oleic acid and methylene blue.

The method of making the membrane-forming pharmaceutical composition was to dissolve and mix the ingredients. 5 g of dichloromethane was mixed with 91.99 g of ethanol. To the produced mixture, 0.01 g of methylene blue was added and beakered. The mixture was then stirred at 20°C to 25°C for 3.5 min at 570 rpm to produce a blue liquid of uniform consistency and characteristic odor. To the obtained solution of non-aqueous methylene blue, 1 g of oleic acid was introduced and stirred at room temperature for 3 min at 620 rpm. To the obtained mixture, 2 g of cellulose ethyl ether was introduced and stirred at room temperature for 7 min at 800 rpm until a colored (blue) liquid of uniform consistency and characteristic odor was obtained.

The formulation thus made containing 2% cellulose ethyl ether was subjected to a study of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h. Commercially available polymer formulations were used as reference During the study, it was shown that the average time to form a tight, flexible coating was 32 sec, which was 6 sec faster than the market formulation. The coating retention time was 120 h, 24 h longer than the market formulation .

Example 8

A membrane- forming pharmaceutical protective composition comprising dichloromethane, ethyl alcohol and cellulose ethyl ether, and the excipients oleic acid and methylene blue.

The method of making the membrane-forming pharmaceutical composition was to dissolve and mix the ingredients. 68.5 g of dichloromethane was mixed with 5 g of ethanol. To the produced mixture, 1.5 g of methylene blue was added and beakered. It was then stirred at 20°C to 25°C for 3.5 min at 570 rpm to produce a blue liquid of uniform consistency and characteristic odor. To the obtained solution of non-aqueous methylene blue, 10 g of oleic acid was introduced and stirred at room temperature for 2 min at 620 rpm. To the obtained mixture, 15 g of cellulose ethyl ether was introduced and stirred at room temperature for 8 min at 800 rpm until a colored (blue) liquid of uniform consistency and characteristic odor was obtained.

The formulation thus made containing cellulose ethyl ether at a concentration of 15% was subjected to a study of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h. Commercially available polymer formulations were used as reference During the study, it was shown that the average time to form a tight, flexible coating was 15 sec. which was 23 faster than the market formulation. The coating retention length was 120 h and was 24 h longer than the market formulation.

Example 9

A membrane- forming pharmaceutical protective composition comprising dichloromethane, ethyl alcohol and cellulose ethyl ether, and the excipients oleic acid and methylene blue.

The method of making the membrane-forming pharmaceutical composition was to dissolve and mix the ingredients. 5 g of dichloromethane was mixed with 68.5 g of ethanol. To the produced mixture, 1.5 g of methylene blue was added and beakered. The mixture was then stirred at 20°C to 25°C for 2 min at 570 rpm to produce a blue liquid of uniform consistency and characteristic odor. To the obtained solution of non-aqueous methylene blue, 10 g of oleic acid was introduced and stirred at room temperature for 2 min at 620 rpm. To the resulting mixture, 15 g of cellulose ethyl ether was introduced and stirred at room temperature for 25 min at 800 rpm until a colored (blue) liquid of uniform consistency and characteristic odor was obtained.

The formulation thus made containing cellulose ethyl ether at a concentration of 15% was subjected to a study of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of the experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h. Commercially available polymer formulations were used as a reference During the study, it was shown that the average time to form a tight, flexible coating was 26 sec. which was 12 sec. faster than the market formulation. The coating retention time was 96 h and was equal to the market formulation.

Example 10

A membrane- forming pharmaceutical protective composition comprising dichloromethane, ethyl alcohol and cellulose ethyl ether and the excipients methylene blue, zinc oxide, anhydrous ointment base, methyl ketone.

The method of making the membrane-forming pharmaceutical composition was to dissolve and mix the ingredients. 90.99 g of dichloromethane was mixed with 5 g of ethanol and 1 g of acetone. To the resulting mixture, 0.01 g of methylene blue was added and beakered. It was then stirred at 20°C to 25°C for 3.5 min at 570 rpm to produce a blue liquid of uniform consistency and characteristic odor. To the resulting mixture, 2 g of cellulose ethyl ether was introduced and stirred at room temperature for 4 min at 800 rpm to produce a colored (blue) liquid of uniform consistency and characteristic odor. To the resulting nonaqueous methylene blue solution, 0.5 g of anhydrous ointment substrate was introduced and stirred at room temperature for 4 min at 620 rpm. 0.5 g of oxide was introduced into the mixture and stirred for 4 min until a uniform blue mixture with a characteristic odor was obtained.

The formulation thus made containing 2% cellulose ethyl ether was subjected to a study of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of the experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h. Commercially available polymer formulations were used as reference During the study, it was shown that the average time to form a tight, flexible coating was 9 sec. which was 29 faster than the market formulation. The coating retention length was 144 h, which was 48 h longer than the market formulation.

Additionally, the above described formulation was applied to the teat canal of experimental animals. The study was conducted for 7 days on 12 teats of three experimental animals (cows) . The study consisted in measuring the retention time of the polymeric mass inside the teat canal, visual and palpation evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 2h, 6h, 12h, 24h, 2 days, 3d days, 4 days, 5 days, 6 days, 7 days. A commercially available injectable preparation was used as reference. The study showed that the average time to form an elastic mass, filling the teat canal, tightly adhering to the canal walls, forming a physical barrier was 4 min. The market formulation did not form a tight elastic mass and did not form a physical barrier, but only coated the mucous membrane of the teat canal. The product of the described formulation remained in the teat canal without traces of leakage until the end of the experiment, which was 7 days, while in the case of the market preparation traces of leakage were observed already after 48 hours .

Example 11

A membrane- forming pharmaceutical protective composition comprising dichloromethane, ethyl alcohol and cellulose ethyl ether and the excipients methylene blue, zinc oxide, anhydrous ointment base, methyl ketone.

The method of making the membrane-forming pharmaceutical composition was to dissolve and mix the ingredients. 5 g of dichloromethane was mixed with 90.99 g of ethanol and 1 g of acetone. To the resulting mixture, 0.01 g of methylene blue was added and beakered. It was then stirred at 20°C to 25°C for 3.5 min at 570 rpm to produce a blue liquid of uniform consistency and characteristic odor. To the resulting mixture, 2 g of cellulose ethyl ether was introduced and stirred at room temperature for 6 min at 800 rpm to produce a colored (blue) liquid of uniform consistency and characteristic odor. To the resulting non-aqueous methylene blue solution, 0.5 g of anhydrous ointment medium was introduced and stirred at room temperature for 8 min at 620 rpm. 0.5 g of oxide was introduced into the mixture and stirred for 4 min until a uniform blue mixture with a characteristic odor was obtained.

The formulation thus made containing 2% cellulose ethyl ether was subjected to a study of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of the experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h. Commercially available polymer formulations were used as a reference During the study, it was shown that the average time to form a tight, flexible coating was 35 sec, which was 3 sec faster than the market formulation. The coating retention length was 96 h and was equal to the market formulation .

Additionally, the above described formulation was applied to the teat canal of experimental animals. The study was conducted for 7 days on 12 teats of three experimental animals (cows) . The study consisted in measuring the persistence time of the polymeric mass inside the teat canal, visual evaluation and palpation. Samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 2h, 6h, 12h, 24h, 2 days, 3d days, 4 days, 5 days, 6 days, 7 days. A commercially available injectable preparation was used as reference. The study showed that the average time to form an elastic mass, filling the teat canal, tightly adhering to the canal walls, forming a physical barrier was 3.5 minutes. The market formulation did not form a tight elastic mass and did not form a physical barrier and only coated the mucous membrane of the teat canal. The product of the formulation described above remained in the teat canal without traces of leakage until the end of the experiment, i.e. 7 days, whereas in the case of the market preparation traces of leakage were observed after 72 hours .

Example 12

A membrane- forming pharmaceutical protective composition comprising dichloromethane, ethyl alcohol and cellulose ethyl ether and the excipients methylene blue, zinc oxide, anhydrous ointment base, methyl ketone.

The method of making the membrane-forming pharmaceutical composition was to dissolve and mix the ingredients. 18.5 g of dichloromethane was mixed with 5 g of ethanol and 30 g of acetone. To the resulting mixture, 1.5 g of methylene blue was added and beakered. It was then stirred at 20°C to 25°C for 3.5 min at 570 rpm until a blue liquid of uniform consistency and characteristic odor was produced. To the resulting mixture, 15 g of cellulose ethyl ether was introduced and stirred at room temperature for 30 min at 800 rpm to produce a colored (blue) liquid of uniform consistency and characteristic odor. To the resulting non-aqueous methylene blue solution, 20 g of anhydrous ointment substrate was introduced and stirred at 30°C for 15 min at 620 rpm until uniform. 10 g of oxide was introduced into the mixture and stirred for 10 min until the mixture was uniform.

The formulation thus made containing cellulose ethyl ether at a concentration of 15% was subjected to a study of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h. Commercially available polymer formulations were used as reference During the study, it was shown that the average time to form a tight, flexible coating was 18 sec. which was 20 faster than the market formulation. The coating retention length was 120 h, which was 24 h longer than the market formulation.

In addition, the above described formulation was applied to the teat canal of experimental animals. The study was conducted for 7 days on 12 teats of three experimental animals (cows) . The study consisted in measuring the retention time of the polymeric mass inside the teat canal, palpation and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 2h, 6h, 12h, 24h, 2 days, 3d days, 4 days, 5 days, 6 days, 7 days. A commercially available injectable preparation was used as reference. The study showed that the average time to form an elastic mass, filling the teat canal, tightly adhering to the canal walls, forming a physical barrier was 4.5 minutes. The market preparation did not form a tight elastic mass and did not create a physical barrier, but only coated the mucous membrane of the teat canal. The product of the formulation described above remained in the teat canal without traces of leakage until the end of the experiment, i.e. 7 days, whereas in case of the market preparation traces of leakage were observed after 72 hours.

Example 13

A film-forming pharmaceutical protective composition comprising dichloromethane, ethyl alcohol and cellulose ethyl ether and the excipients methylene blue, zinc oxide, anhydrous ointment base, methyl ketone. The method of making the membrane-forming pharmaceutical composition was to dissolve and mix the ingredients. 5 g of dichloromethane was mixed with 18.5 g of ethanol and 30 g of acetone. To the resulting mixture, 1.5 g of methylene blue was added and beakered. It was then stirred at 20°C to 25°C for 3.5 min at 570 rpm to produce a blue liquid of uniform consistency and characteristic odor. To the resulting mixture, 15 g of cellulose ethyl ether was introduced and stirred at room temperature for 35 min at 800 rpm to produce a colored (blue) liquid of uniform consistency and characteristic odor. To the resulting non-aqueous methylene blue solution, 20 g of anhydrous ointment substrate was introduced and stirred at 30°C for 15 min at 620 rpm until uniform. 10 g of oxide was introduced into the mixture and stirred for 10 min until the mixture was uniform.

The formulation thus made containing cellulose ethyl ether at a concentration of 15% was subjected to a study of the rate of formation of an elastic polymeric film on the hydrophilic fluid and the length of persistence of this film on the skin surface of experimental animals. The study was conducted for 8 days on 12 teats of three experimental animals (cows) . The study consisted of measuring the coating retention time and visual evaluation. The samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 3h, 6h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h, 192h. Commercially available polymer formulations were used as reference During the test, it was shown that the average time to form a tight, flexible coating was 32 sec, which was 6 sec faster than the market formulation. The coating retention length was 96 h and was equal to the market formulation.

Additionally, the above described formulation was applied to the teat canal of experimental animals. The study was conducted for 7 days on 12 teats of three experimental animals (cows) . The study consisted in measuring the retention time of the polymeric mass inside the teat canal, palpation and visual evaluation. Samples were evaluated continuously from the time of application for the first 30 min. then at intervals of 1 h, 2h, 6h, 12h, 24h, 2 days, 3d days, 4 days, 5 days, 6 days, 7 days. A commercially available injectable preparation was used as reference. The study showed that the average time to form an elastic mass, filling the teat canal, tightly adhering to the canal walls, forming a physical barrier was 5 min. The market formulation did not form a tight elastic mass and did not form a physical barrier, but only coated the mucous membrane of the teat canal. The product of the formulation described above remained in the teat canal without traces of leakage until the end of the experiment, i.e. 7 days, whereas in the case of the market preparation traces of leakage were observed after 48 hours .