Biodegradable plaster

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a biodegradable plaster containing at least one bioadhesive layer, and at least one non-bioadhesive layer with the bioadhesive layer containing at least one polyarphon dispersion, and at least one bioadhesive polymer with the polyarphon dispersion containing at least one pharmacologically active substance.

EFFECT: biodegradable plaster can deliver drugs, including poorly water soluble ones.

21 cl, 8 ex

 

This invention relates to boorstosima the patch containing the pharmaceutically active substance. The composition is designed to adhere to the surfaces of the body of mammals and, in particular, to the surface of the skin and/or mucous membranes of mammals, and makes possible local delivery of pharmaceutically active funds in specific designated place.

Bioadhesive media known to specialists in this field and include gels, pastes, tablets and film. Usually mucoadhesive tools presented in the form of a film or tape, which are designed for gluing when applied to the mucous membrane.

Recently developed biorstwami device having bioadhesive layer and aboutgenwhy layer. For example, in US 5800832 described water-soluble, bioreserve pharmaceutical device for delivery to be applied on the surface of mucous membranes. The device consists of an adhesive layer and not the adhesive protective layer. However, the device for delivery to US 5800832 has the disadvantage that the pharmaceutically active substance may be compatible with the ingredients of layers, which can lead to the deposition of the active substance. In this case, the active substance may not be evenly distributed in the layers of this composition. Such incompatibility may prevent you include all the group of active substances in mucoadhesive device.

In the US 2003/0194420 A1 describes bioreserve, water-soluble media device containing aboutgenwhy protective layer, bioadhesive layer and the composition containing the active ingredient, whereby the composition is applied to the surface or aboutgetting protective layer layer, or bioadhesive layer after the formation of biorazlagaemykh, water-soluble media device. Unlike US 5800832 US 2003/0194420 A1 describes a method for mucoadhesive device, which is based on the application of active substances to the surface of this device. One of the drawbacks US 2003/0194420 A1 is that the active substance will not be evenly distributed in containing the active substance layer of the device, and as a result there will be no possibility of controlled release.

There is a need to solve at least some problems pharmaceutical devices for delivery, known from the prior art. In particular, there is a need to develop biorazlagaemykh patch that can deliver a wide range of medicines, including those that are poorly soluble in water.

Accordingly, presents birthdaaay plaster containing at least one bioadhesive layer and at least one aboutgenwhy layer, and bioadhesive layer contains at IU is e, one polyamoury dispersion and at least one bioadhesive polymer, and poliarnaia dispersion contains at least one pharmacologically active substance.

In accordance with another aspect of the present invention presents the use of the patch for the treatment of disorders, infections or diseases. In particular, in accordance with another aspect of the present invention is provided the use of a patch for the treatment of depression, diabetes, addiction to drugs, epilepsy, fungal infections, gout, hypertension, malaria, migraine headaches, Parkinson's disease, cancer, viral infections, bacterial infections, eczema, local and systemic pain, elevated cholesterol levels, inflammation, insomnia, protozoal infections, worms, tapeworms, arrhythmia, thrombosis, angina, allergic reactions, disorders of the thyroid, psoriasis, swelling, or gastrointestinal infections.

In accordance with another aspect of the present invention presents the use of the described patch for the manufacture of a medicine for the treatment of depression, diabetes, drug addiction, epilepsy, fungal infections, gout, hypertension, malaria, migraine headaches, Parkinson's disease, cancer, viral infections, bacterial infections, eczema, local or systemic pain high cholesterol, inflammation, insomnia, protozoal infections, worms, tapeworms, arrhythmia, thrombosis, angina, allergic reactions, impaired balance thyroid, psoriasis, swelling, or gastrointestinal infections.

In accordance with another aspect of the presented method of manufacturing the patch, including the formation of polifroni dispersion comprising pharmaceutically active agent; mixing specified polifroni dispersion and bioadhesive polymer with the formation of bioadhesive layer and receive on the specified bioadhesive layer aboutgetting layer.

In accordance with another aspect of the presented method of manufacturing the patch, including the formation of aboutgetting layer; and receive on the specified naviadesign.com layer bioadhesive layer, and bioadhesive layer contains polyamoury dispersion containing a pharmacologically active substance and bioadhesive polymer.

Under polihronova dispersion in accordance with the description refers to a special kind of dispersion of hydrophilic liquid-in-hydrophobic hydrophobic liquid or liquid-in-hydrophilic liquid comprising (a) a hydrophilic liquid immiscible phase, (b) a second hydrophobic phase, which is immiscible or substantially immiscible with the first phase and (C) one or more surface-the active substances (surfactants), moreover, the dispersed or dispersed phase is in the form of small (for example, from the micron to sub-micron diameter, but usually at least a diameter of 1 micron) droplets, and generally have the following characteristics that distinguish Polyarnaya variance from conventional emulsions and other types of dispersions:

1. They can exist in a stable form, and volume fraction of dispersed phase (φip) is more than 0.7 and can be 0,97 (φiprepresents the volume ratio of dispersed to continuous phase, expressed as a proportion).

2. Microscopic picture poliamidowych dispersions, where ϕipmore than 0.7, such that consists of an Assembly of individual droplets, closely compressed together in polyhedrally forms reminiscent of the type of gas saturated foam. In this form, the dispersion has a gel-like properties and is called the gel polihronova dispersion (GPD).

3. Stable Polyarnaya dispersion can be formed when the surfactant concentration is less than 3%, and more typically, less than 2% by weight on the total composition.

4. Gel Polyarnaya dispersion (described in paragraph 2 above) can be diluted to any extent by adding more continuous phase without the addition of additional quantities of surfactants, when properties gelatoria disappear. When ϕp reduced to below 0.7, the individual droplets of the internal phase become separated, so that take the form of spherical droplets, which remain stable and unchanged, but which, nevertheless, can be connected together in a loose Association and float up or sink to the bottom of the diluted dispersion (depending on the relative density of the two phases). In this diluted form, each bit is called a colloidal liquid afron (CLA). A simple shake of the diluted dispersion immediately causes the formation of a stable dispersion of colloidal liquid Aronov.

Each of the above characteristics and their combination clearly differentiates Polyarnaya dispersion of the present invention from conventional emulsions and dispersions of other types that do not possess all these characteristics. Polyarnaya dispersion are described in the following literature sources Sebba: “Biliquid Foams”, J. Colloid and Interface Science, 40 (1972) 468-474 and The Behaviour of Minute Oil Droplets Encapsulated in Water Film”, Colloid Polymer science, 257 (1979) 392-396, Hicks “Investigating the Generation, Characterization, and Structure of Biliquid Foams”, PhD Thesis, University of Bristol, 2005, Crutchley “The Encapsulation of Oils and Oil Soluble Substances Within Polymer Films”, PhD Thesis, The University of Leeds, 2006 and Lye and Stuckey, Colloid and Surfaces, 131 (1998) 119-136. Efroni also described in US-A-4486333 and WO 97/32559.

Polyarnaya dispersion are sometimes called "two-fluid foams, emulsions with a high content of internal f is s (HIPEs)", "emulsion with a high ratio of internal phase (HIPREs)" and "gel-like emulsion". All descriptions, which are dispersions having the characteristics described above are poliarnoye the dispersions used in this invention.

Every aspect of that described, may be combined with any(and) other aspect or aspects, unless expressly stated otherwise. In particular, any feature that is specified as being preferred or advantageous may be combined with any(s) other(them) characteristic or characteristics specified as being preferred or preferential.

Birthdaaay the patch of the present invention can be used for localized treatment of body tissue, diseases or wounds. It can be applied on the skin, to enable transdermal delivery of active substances.

The patch can be particularly useful when applied to wet the surface of the body of mammals, which receives body fluid, such as the mouth or other mucous surfaces. Mucous surfaces include, but are not limited to, the surface of the cornea, conjunctiva, nose, cheeks, sublingual, lungs, stomach, intestines, uterus, bladder, rectum and vagina.

When applying and attaching the patch to this izobreteny is on the surface, and preferably, the mucous surface, the pharmaceutically active substance is delivered to the planned location in the surrounding tissue and other body fluids. This device preferably provides an appropriate time presence at the place of application for effective drug delivery.

Suddenly discovered that can be taken in respect of at least some of the compatibility issues (uniform distribution), registered in the prior art, between the particular polymers and pharmaceutically active substances. In particular, measures against these problems can be made by forming bioadhesive layer containing bioadhesive polymer and polyamoury dispersion, and poliarnaia dispersion contains at least one pharmaceutically active substance. The polymer comprising polyamoury dispersion can be formed into one homogeneous mass, able to be molded into a desired shape. Such bioadhesive layers provide controlled release of pharmaceutically active(s) of the substances(a) within a certain period of time, when the polymer is dissolved and/or destroyed. As poliarnaia dispersion can be distributed throughout the area, and preferably evenly distributed over bioedge the active layer, can be achieved essentially constant characteristics of the release of pharmaceutically active substances. In addition, the pharmaceutically active substance can be uniformly distributed in bioadhesive layer in solvated form. It is particularly favorable for soluble oil active substances in which the active substance can be dissolved in the oil phase of polihronova dispersion.

One of the advantages biorazlagaemykh patch of the present invention is that when the patch is, for example, in the cheek cavity, the presence of aboutgetting layer helps direct the release of pharmaceutically active substances through the mucous membrane. This reduces the inefficient loss of the active substance in the mouth and therefore improves the efficiency of drug delivery. In addition, as the pharmaceutically active substance may be present in the dissociated form in polihronova dispersion achieves good penetration into the mucosa or skin and other surfaces of the body. Thus, birthdaaay the patch of the present invention enables delivery of pharmaceutically active substances in high concentrations in specific localization in the appropriate form to allow sufficient absorption of the che is owaka and animals. In addition, as the pharmaceutically active substance can be dissolved in a suitable solvent, you can get the patch containing the pharmaceutically active substance in an appropriate concentration (for the particular use for which it was designed patch) for enhanced delivery, for example, in the mucous membrane.

An additional advantage of this invention is provided by the properties poliamidowych dispersions. In this invention poliarnaia variance contained in borisloseso the patch. When birthdaaay patch is dissolved and/or dispersed, drops polihronova dispersion are released and remain in the form of individual droplets. Released Polyarnaya droplets are therefore able to exist as a discrete and separate elements with minimal risk of merging with larger droplets. Thus, individual droplets retain their high surface area, through which molecules pharmaceutically active substances can diffuse into or through the mucous membrane for local or systemic absorption. This is in contrast with, for example, emulsions, and if the emulsion is contained in a polymer matrix, when the polymer matrix is dissolved, the emulsion has a tendency to coalesce.

An additional advantage Yes the tion of the invention, more than one poliarnaia dispersion may be present in the patch. Each poliarnaia dispersion may contain one or more pharmaceutically active substances that may be present in the continuous or dispersed phase. This gives you the opportunity to get the patches, which may include pharmaceutically active substances that are incompatible with each other, using traditional shipping methods that you want to deliver at the appointed place in one and the patch without any unwanted problems in terms of stability.

The term "birthdaaay patch" in accordance with the description means that when the patch is used on the surface of the body of a person/animal, the components of the patch are dispersed and/or dissolved in the prevailing conditions, so poliarnaia variance, and hence pharmaceutically active substance is released from the patch. This allows the adhesive to melt/decompose within a certain period of time, and natural body fluids slowly dissolve and destroy the patch. In addition, or alternatively, physical abrasion patches on the body surface of a person/animal can help the dispersion and/or dissolution of plaster. Unlike bandages, transdermal funds and other water-insoluble planon the x systems, the user must not delete the patch after treatment.

Preferably, the patch is made so that when it contacts with water or aqueous environment (such as saliva, gastric juice or plasma from open wounds), the patch is destroyed and/or dissolves, releasing polyamoury dispersion and a pharmaceutically active substance.

Suitable polymers for use in this invention can be dispersible in water and/or water-soluble. Alternative or in addition, this polymer can be dissolved in acid. Decomposition biorazlagaemykh patch can occur as a result of acidic/alkaline conditions and/or activity of the enzyme on the polymer in the composition of the patch. By careful selection of the polymer(s) in bioadhesives/naviadesign.com layers of velocity dispersion and/or dissolution of the layers can be adjusted. It also allows you to change the rate of release of pharmacologically active(s) means(a).

Appropriate time of destruction/dissolution will depend on the intended use of the patch. When the patch is intended for use in the mouth are usually at least 50%, more preferably at least 60%, more preferably at least 80% bioadhesive layer will disintegrate and/or dissolve within 20 minutes, more preferably within 10 minutes, more p is edocfile, within 7 minutes after placing in the sublingual cavity. It is clear that when birthdaaay the patch is designed for application on the skin, the rate of disintegration and/or dissolution bioadhesive layer mainly will be much slower. For use on the skin destruction and/or dissolution bioadhesive layer may take from minutes to hours or days, depending on the choice of components.

Bioadhesive layer contains bioadhesive polymer. In accordance with the description of the term "bioadhesive polymer" refers to a polymer that adheres to biological surfaces, such as mucous membrane or skin tissue, preferably for a long period of time.

Bioadhesive polymers, which are known to experts in this field, for example, from US 5474768. Example 2 in US 5474768 describes the determination of the force required to separate two layers of freshly isolated tissue of the stomach of a rabbit, which are glued to each other bioadhesive polymer. Using the techniques described in this example, bioadhesive the polymer may be defined as a substance that requires the efforts of at least about 50 Dyne/cm2to separate two bonded newly allocated piece of tissue of the stomach of the rabbit.

It will be clear that while bioadhesive layer is designed to adhere to the mucous on the ernestam skin tissue, aboutgenwhy layer is designed so that it will not significantly adhere to such surfaces. So when, for example, birthdaaay the patch of the present invention is intended for sublingual use, bioadhesive layer will adhere to tissue of the mucous in the sublingual region, and will be removed in a peeling under normal use until, until biodegradation (and delivery of medicines). In this example, aboutgenwhy layer will be enough nabyudeniem that he did not stick to the language, and will therefore be excluded competitive adhesion, which can lead to peeling of the patch.

Suitable bioadhesive polymers include polyacrylic acid, modified polyacrylic acid, sodium carboxymethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, polyvinylpyrrolidone, etilzelluloza, hydroxypropylcellulose, hypromellose, polyvinyl alcohol, hydroxyethylmethylcellulose, methylcellulose, hyaluronic acid, polysaccharides, pectin, chitosan, pullulan, tragakant, sodium hyaluronate, Arabian gum, modified starches and Gantrez polymers (copolymers metilfenidato ether and maleic anhydride) and mixtures thereof. Preferably, bioadhesive layer contains polyvinyl alcohol. These polymers can be p churromania. It will be clear that other bioadhesive polymers can be used in this invention if they have a suitable mucoadhesive and/or binding properties to the skin.

The degree of bioadhesive will improve due to molecular weight and the functionality (and in the case of polyvinyl alcohol with a degree of hydrolysis). The person skilled in the art will be well-known brands of polymers for use in bioadhesive.

It will be understood that the form of the polymer can affect bioadhesive patch. If the polymer is partially gidratirovana before applying at the point of use, usually bioadhesive will be worse than if the polymer dehydration, and then, later, gidratirovana with the environment at the place of use. Further hydrating the polymer may result from, for example, interaction with the mucous membranes, saliva and/or blood.

Bioadhesive layer preferably contains from 1 to 99% by weight bioadhesive polymer, more preferably from 10 to 70% by weight, more preferably from 10 to 70% by weight, even more preferably from 40 to 60% by weight bioadhesive layer as a whole.

Bioadhesive layer and/or aboutgenwhy layer in this invention may include a film forming polymer. Suitable film forming polymers known to specialists in this area and include, but not limited to, acetylcellulose, acetylbutyrate, polyvinylpyrrolidone, polyvinyl alcohol, maltodextrin, pullulan, modified starches, polyacrylic acid (high molecular weight), acetaldehyde, polyvinylpyrrolidone/polyvinyl acetate copolymer, xanthan gum, copolymers of lactic acid, caprolactone and glycolic acid and their mixtures. Sewn or plasticized film-forming polymers can be used to change the kinetics of dissolution of layers.

Aboutgenwhy layer preferably contains from 0 to 99% by weight of film-forming polymer, more preferably from 0 to 30% by weight, more preferably from 0 to 10% of the total weight aboutgetting layer.

Other suitable for use polymers in bioadhesive and/or aboutgetting layers can undergo Sol-gel transition due to temperature changes (e.g., gelatin) or by structure (for example, structuring alginate salts with calcium ions) and include, for example, gelatin, pectin, agar-agar, carrageenan, alginates, other dispersible or soluble in water forming polymers known in the art. Mixtures of the above can also be used in this invention. Preferred polymers include gelatin and arraynew gum. Most preferably, this polymer is gelatin.

To form the patch or part of a patch, you can also use the dried powder of the polymer. Examples of suitable polymers in powder form include, but are not limited to, a modified polyacrylic acid (for example, a Noveon AA-1, Carbopol 974), gantrez polymers and carboxymethylcellulose.

The plasticizer or a mixture thereof can be used in this invention to make birthdaaay patch more elastic and soft. Plasticizers can be selected, for example, from the group consisting of a polyalcohol organic acids, acids and hydroxyl groups, amines, amine acids, sulfoxidov and pyrrolidone. In the preferred embodiment of this invention, the plasticizer is chosen from the group consisting of sorbitol, mannitol, glycerol, xylitol, maldita (maltisorb®; maltisorb), propylene glycol, polyethylene glycol, lactate, trehalose, esters of sorbitol and arbitragefree and mixtures thereof.

Bioadhesive layer preferably contains from 0 to 30% by weight plasticizer, more preferably from 5 to 20% by weight, more preferably from 10 to 15% by weight, all percentages presented in the calculation of the total weight bioadhesive layer.

Aboutgenwhy layer preferably contains from 0 to 35% by weight of plasticizer, more predpochtitel is about, from 5 to 20% by weight, more preferably from 10 to 15% by weight, all percentages presented in the calculation of the total weight aboutgetting layer.

It will be clear that the consistency of the layers of the patch may vary from gel-like consistency to a solid consistency by careful selection of ingredients.

It will be understood that the number and choice of plasticizer will help to set the hardness of the final product. It can also affect the disintegration and/or dissolution of the molded body and its physical and chemical stability.

The polymers used in layers according to this invention, can be chosen so that they are sensitive to the acidity or alkalinity so that the release of enabled(s) pharmacologically active(s) of the substances(a) can be determined by changing the pH or by the presence of other chemical species.

Birthdaaay the patch of the present invention preferably contains from 1 to 95% by weight bioadhesive layer, more preferably from 10 to 40% by weight, more preferably from 15 to 25% by weight from just biorazlagaemykh patch.

Birthdaaay the patch of the present invention preferably contains from 5 to 99% by weight aboutgetting layer, more preferably from 60 to 90% by weight, more preferably from 75 to 85% by weight from biorazlagaemykh patch in General.

Near the question was found, what amount of polihronova dispersion in bioadhesive layer can be as high as 60% by weight from bioadhesive the whole layer. Preferably, the amount of polihronova dispersion in bioadhesive layer is at least 20%, more preferably at least 30%, more preferably at least 40% by weight from bioadhesive the whole layer. Preferably, the dispersed phase of polihronova dispersion contains a pharmaceutically acceptable oil phase. Examples of oils that can be used in the dispersed phase of Aronov include almond oil, babassu oil, black currant seed oil, borage seed oil drug, canola oil, castor oil, coconut oil, cod liver oil, corn oil, cottonseed oil, evening primrose oil, fish oil, stone fruits, grape seed oil, mustard oil, olive oil, palm stone fruit oil, palm oil, peanut oil, rapeseed oil, Safronova oil, sesame oil, squalane, soybean oil, sunflower oil, walnut oil, wheat germ oil, gidrirovannoe castor oil, gidrirovannoe palm oil, gidrirovannoe soybean oil, partially gidrirovannoe soybean oil, gidrirovannoe vegetable oil, modified triglycerides, Kapralova/capric glycerides, fractionated triglycerides, glyceri tricaprate, glyceryltrinitrate, glyceryltrinitrate, glyceryltrinitrate/capret, glyceryltrinitrate/capret, glyceryltrinitrate/capret/laurate, glyceryltrinitrate/capret/linoleate, glyceryltrinitrate/capret/stearate, glyceryltrinitrate, glyceryltrinitrate, glyceryltrinitrate, glyceryltrinitrate, glycerides of linoleic acid, saturated poliglecaprone glycerides, synthetic medium chain triglycerides, containing the main circuit With8-C12fatty acids, medium chain triglycerides, long-chain triglycerides, modified triglycerides, fractionated triglycerides, and mixtures thereof.

Examples of mono - and diglycerides, which can be used in this invention include mono - and diesters of propylene glycol having from 15 to 40 carbon atoms, including gidrolizovannogo coconut oil (e.g., Capmul MCM), gidrolizovannogo corn oil (for example, Maisine 35-1).

Monoglycerides and diglycerides are complex mono - or diesters of glycerol and a saturated fatty acid having a chain length from eight to sixteen carbon atoms.

Essential oils can also be used in this invention.

The oil can be added a suitable antioxidant.

Preferably, bioadhesive layer contains from 1 to 60% by weight pharmaceutically acceptable oil, more preferred the equipment, from 10 to 50% by weight, more preferably from 20 to 40% by weight of the weight of bioadhesive layer as a whole.

Preferably, the continuous hydrophilic phase of polihronova dispersion contains water. Continuous hydrophilic phase may further comprise a co-solvent such as an aliphatic alcohol, a glycol, propylene glycol or glycerol, or mixtures thereof, and/or gelling agent, thickener, rheology modifier and stabilizer. Suitable gel-forming substances include alginate resin or their salts, guar gum, carob bean gum, xanthan gum, gum acacia, gelatin, hydroxymethylcellulose, hydroxyethyl cellulose, hydroxypropylcellulose, carboxymethyl cellulose or its salt, bentonites, silicates of magnesium, "Carbonari" (salt structured polymers of acrylic acid) or glyceryltrinitrate or their dispersion in the glycols, or polyvinylpyrrolidones polymer or dispersible in water, the copolymer, or any suitable mixture of any of these polymers and gums.

Alternatively, the hydrophilic phase may be non-aqueous or substantially non-aqueous. The hydrophilic phase may be, for example, aliphatic alcohol, polyethylene glycol, propylene glycol or glycerol, or mixtures thereof.

Surfactants used in this invention can be included in one of the if in both phases polihronova(s) variance(s). Surfactants used in this invention preferably are alkylpolyglycoside simple ether, alkylpolyglycoside ester, ethoxylated alcohol, an ester of polyoxyethylenesorbitan and fatty acid ester of polyoxyethylene and fatty acids, ionic and non-ionic surfactants, adducts, hydrogenated castor oil/polyoxyethyleneglycol containing from 25 to 60 taksigrup, adduct of castor oil/glycol containing from 25 to 45 taksigrup, esters of sorbitol and fatty acids (e.g., Span 20 and span 80), block copolymers of ethylene oxide and propylene oxide (for example, Pluronic L121 or Pluronic F68) or their mixture.

It will be clear that it is possible to use other suitable surfactants.

Preferably, the biodegradable adhesive of this invention contains less than 5% by weight surfactant, more preferably, less than 2% by weight, more preferably, less than 1% by weight from biodegradable patch.

Pharmaceutically active substance may be present mainly in one: either in the continuous or dispersed phase of polihronova dispersion. Alternatively, the pharmaceutically active substance may be present essentially as in the continuous and dispersed phase. This will be partially determined by the solubility of the pharmaceutically active substance in a specific phase.

Preferably, bioadhesive layer will emerge from 0.0001 to 60% by weight of pharmaceutically active substances, more preferably, from 0.1 to 50% by weight, more preferably from 1 to 30% by weight of the weight of the biodegradable patch in General. However, it will be clear that the preferred amount of pharmaceutically active substances will depend on a number of factors. For example, it will depend on the proposed method of application of the patch, i.e. transdermal or sublingual, from the specific pharmaceutically active substances, the solubility of the active substance and purpose of the treatment.

When the pharmaceutically active substance is poorly soluble in water substance", preferably, when it is dissolved in the oil phase of polihronova dispersion. In accordance with the description of the term "poorly water soluble" means a medicinal substance that will dissolve in water at less than 1% by weight. In this embodiment, it may be useful to use simulator for the formation of polihronova dispersion in a quantity sufficient to complete the solubilization of poorly soluble drug substances. Suitable simulation is phosphoglyceric, a phospholipid, such as lecithin or a free fatty acid which is liquid at room temperature, for example, ezoterikova acid, oleic acid, linoleic acid or linolenic acid.

Pharmaceutically active the e tool for example, can be selected from analgesic or anti-inflammatory drugs, deworming drugs, antiarrhythmic agent, anticoagulant tools, antidepressant tools, antidiabetic agents, ANTIEPILEPTICS tools, antifungal agents, antipodagriceski tools, antihypertensive agents, antimalarial assets, migraine, means antimuskarinovoe act occurs, antineoplastic agents, Antiprotozoal tools, antithyroid tools, anxiolytic, sedative, hypnotic, or neuroleptic drugs, corticosteroids, diuretics, anti-Parkinson agents; agents used to treat diseases of the gastrointestinal tract, an antagonist of histamine H1-receptors that regulate lipid assets, angina, tools for treatment thyroid, nutritional agent, antipyretic agent, an antibacterial agent, an immunosuppressant, an antiviral agent, hypothalamic hormones, pituitary hormones, sex hormones, prostaglandins, vaccines, suppression of cough, local anesthetics, immunoglobulins and antisera, opioid analgesics, stimulants, viral vectors for gene therapy or therapeutic mixture.

Preferably, the stimulator is the tsya nicotine.

Examples of pharmacologically active agents that can be used in this invention include the following:

Analgesics and anti-inflammatory ingredients: aceclofenac, aloxiprin, auranofin, azapropazone, buprenorphine, benorilate, capsaicin, celecoxib, diflunisal, etodolac, fenbufen, fenoprofen-calcium, flurbiprofen, ibuprofen, ibuproxam, indomethacin, Ketoprofen, lornoxicam, melinat, mefenamovaya acid, meloxicam, nabumetone, naproxen, nimesulide, oxyphenbutazone, phenylbutazone, piroxicam, refecoxib, sulindac, skibotn, tolmetin, zileuton.

Deworming drugs: albendazole, bephenium, hydroxynaphthoate, dichlorophen, ivermectin, mebendazole, oxfendazole, oxantel, praziquantel, Pyrantel, thiabendazol.

Antiarrhythmic agent: amiodarone, disopyramide, quinidine sulfate.

Antibacterials: beatlespennylane, cinoxacin, ciprofloxacin, clarithromycin, clofazimine, cloxacillin, doxycycline, erythromycin, ciprofloxacin, imipenem, nalidixic acid, nitrofurantoin, rifampin, spiramycin, sulfabenzamide, sulfadoxine, sulfamerazine, sulfacetamide, sulfadiazine, sulfafurazole, sulfamethoxazole, sulfapiridin, tetracycline, trimethoprim, refrasil, guidikova acid, mupirocin, nifuroxazide, oxacillin, sparfloxacin, sulfadoxine, telithromycin, tro is ofloxacin.

Anticoagulants: difenacoum dipyridamole, nicoumalone, phenindione, clopidogrel, tirofiban.

Antidepressants: amoxapine, maprotiline, trimipramine, paroxetine, sertraline.

Antidiabetic agents: acetohexamide, hlorpropamid, glibenclamide, gliclazide, glipizide, tolazamide, insulin, tolbutamide, rosiglitazone, pioglitazone, andgeneral.

Anti-epileptic tools: reclamed, carbamazepine, clonazepam, ethotoin, Meton, methsuximide, methylphenobarbital, phenacemide, phenobarbital, phenytoin, phensuximide, primidone, Altium, valproic acid, tiagabine.

Antifungal agents: azithromycin, oxiconazole, tolnaftate, voriconazole, amphotericin, butoconazole nitrate, clotrimazole, econazole nitrate, fluconazole, griseofulvin, Itraconazole, ketoconazole, miconazole, natamycin, sulconazole nitrate, terbinafine, terconazole, tioconazole, undecenoate acid.

Funds from gout: allopurinol, probenecid, sulfinpirazon.

Antihypertensive agents: amlodipine, benidipine, candeleteselection, clonidine, durodie, diazoxide, eprosartan, felodipine, irbesartan, irinotecan, isradipine, losartan, Minoxidil, nicardipine, nifedipine, nimodipine, prazosin, raubasine, reserpine, tamsulosin, telmisartan, valsartan.

Antimalaria tools: amodiaquine, chloroquine, halofantrine, mefloquine, proguanil, Piri is etamin, quinine sulfate.

Funds from migraines: digidroergotamina mesilate, ergotamine, methysergide, pizotifen, aspirated, eletriptan, frovatriptan, lisuride, naratriptan, rizatriptan, sumatriptan, zolmitriptan.

Antimuskarinovoe act occurs means: atropine, benzhexol, biperiden, giostsiamin, mepenzolate, tropikamid.

Antineoplastic agents and immunosuppressants: aminoglutethimide, amsacrine, anastrazole, azathioprine, bikalutamid, busulfan, chlorambucil, clobetasol, cyclosporine, dacarbazine, estramustine, etoposide, exemestane, gefitinib, letrozole, lomustin, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, mitozantrone, mycophenolate-mofetil, nilutamide, paclitaxel, procarbazine, sirolimus, tacrolimus, tamoxifen, testolactone, toremifen.

Antiprotozoal tools: kliohinol, diethylacetanilide, diloxanide, dinitolmide, furazolidone, metronidazole, nitrofurazone, tinidazole, atovaquone, Ornidazole.

Protivomaskitnye tools: carbimazole, propylthiouracil.

Antiviral agents: the adefovir dipivoxil, APV, efavirenz, lopinavir, nelfinavir, penciclovir, ritonavir, saquinavir, tipranavir.

Anxiolytics, sedatives, hypnotics and antipsychotics: aripiprazole, eszopiclone, paroxetine, sertindole, zaleplon, zolpidem, alprazolam, amylobarbitone, barbiton, bromazepam, bromperidol, broughty the Olam, butobarbital, carbromal, chlordiazepoxid, hlormetiazola, chlorpromazine, clobazam, clozapine, diazepam, droperidol, ethinamate, fluanisone, flunitrazepam, fluororesin, flupentixol decanoate, fluphenazine decanoate, flurazepam, haloperidol, lorazepam, lormetazepam, medazepama, meprobamate, methaqualone, midazolam, nitrazepam, oxazepam, pentobarbital, perphenazine pimozide, prochlorperazine, sulpiride, temazepam, thioridazine, triazolam, zopiclone.

Beta-blockers: nadolol, pindolol.

Broncholytic and anti-asthma drugs: zafirlukast, zileuton.

Cardiac inotropic tools: digitoxin, digoxin, lanatoside With, methoxy.

Corticosteroids: beclomethasone, betamethasone, budesonide, cortisone acetate, desoximetasone, dexamethasone, fludrocortisone acetate, flunisolide, fluocortolone, fluticasone propionate, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone, clobetasol, clobetasone, desonide, mometazon, rimexolone.

Diuretics: acetazolamide, amiloride, bendrofluazide, bumetanide, chlorothiazide, chlorthalidone, ethacrynic acid, furosemide, metolazone, spironolactone, triamterene.

Antiparkinsonian tools: parlodel, apomorphine selegiline.

Funds from erectile dysfunction: sildenafil, vardenafil, tadalafil.

Tools for the treatment of gastrointestinal diseases: encore is Odil, cimetidine, Diphenoxylate, domperidone, famotidine, loperamide, droperidol, dronabinol, nabilone, palonosetron, granisetron, ondansetron, pizotifen, mesalazin, omeprazole, sulfasalazin.

Antigistaminny tools: Cinnarizine, cyclizine, cyproheptadine at, dimenhydrinate, meclozine, oxatomide, terfenadine, acrivastine, antazoline, azatadine, azelastine, bramsen (bromodiphenhydramine), brompheniramine, buclizine, carbinoxamine, kabalin, carebastine, cetirizine, chlorcyclizine, chlorphenamine (chlorpheniramine), chlorphenoxamine, chlorpicrin, clematis, klonipin, cyclizine, cyproheptadine at, leptropin, desloratidine, diphenylhydramine, dimenhydrinate, diphenylpyraline, doxylamine, Bastin, bramin, emedastine, epinastine, Fexofenadine, flunarizin, Galperin, histaprin, homochlorcyclizine, hydroxyzine, isothipendyl, levocabastine, loratadine, mebhydrolin meclozine, mefenidramium, mepyramine, mequitazine, methdilazine, mizolastine, olopatadine, oxatomide, examination, phenindamine, Pheniramine, phenyltoloxamine, pemmican, promethazine, propiomazine, pyrobitumen, rupatadine, setaction, falastin, temelastine, terfenadine, tietilperazin, trimethobenzamide, tripelennamine, triprolidine, tritoqualine.

Regulating the level of lipids tools: bezafibrat, clofibrate, lovastatin, pravastatin, rosuvastatin, simvastatin, fenofibrate, gemfibrozil, probucol.

Nutritional agents: beta carotene, vitamin a, vitamin B2, vitamin D, vitamin E, vitamin K, vitamin B12.

Opioid analgesics: codeine, dextropropoxyphene, diamorphine, Dihydrocodeine, meptazinol, morphine, pentazocine, fentanyl.

Sex hormones: clomiphene, danazol, levonorgestrel, medroxyprogesterone acetate, mestranol, methyltestosterone, norethisterone, norgestrel, estradiol, conjugated estrogens, progesterone, stanozolol, stilbestrol, testosterone, tibolone.

Stimulants: dexamfetamine, dexfenfluramine, mazindol, nicotine.

The viral vector may be a retrovirus (such as a virus murine Moloney leukemia), lentivirus, adenovirus, adeno-associated virus (AAV) or created by nanosubstance, such as Ormosil.

The active substance may be a monoclonal antibody.

These medicines can be replaced by their pharmaceutically acceptable salts, isomers and derivatives. Pharmaceutically applicable salts include, for example, hydrochloride, maleate, tartrate, embanet. When it is therapeutically effective, it is possible to use a mixture of pharmacologically active agents.

Biodegradable patch of the present invention is preferably presented in a complete dosage form. Each dosage in PLA the four may contain from 0.05 mg to 500 mg, and, in particular, from 0.1 mg to 20 mg of a pharmaceutically active substance. It will be clear that the preferred dosage is one application will depend on the specific pharmacologically active substance and the intended method of application of the patch.

When the patch is cheek or sublingual patch, can be also added some taste of funds. You can use any suitable number and any type of artificial and/or natural flavouring substances touch any suitable manner. For example, a flavoring may be from 0.1% to 20% by weight of the weight of plaster in General, preferably from 0.5% to 5% by weight. Improves the taste and odor means may include, for example, essential oils, synthetic flavors or mixtures thereof including, but not limited to, oils derived from plants and fruits such as citrus oils, fruit essences, peppermint oil, oil curly mint, other mint oils, clove oil, oil of gaultheria, anise and the like, components flavour with killing microorganisms properties, such as menthol, eucalyptol, thymol, and combinations thereof.

The patch can also be included dyes. These dyes may include, for example, natural food colors and dyes suitable for use in a medicinal product which, and may be present in amounts of from 0.01% to 1.5% by weight from the patch in General.

In the preferred embodiment aboutgenwhy layer includes improving the taste and odor of the substance and/or dye.

In another embodiment aboutgenwhy layer includes at least one polyamoury dispersion. Poliarnaia dispersion may contain improving the taste and odor of the substance, coloring, taste masking composition and/or odorant or neutralizing/masking the smell of the component.

The patch of the present invention may include a clouding (silencer) or a mixture of cloud emulsions. Cloud can be added to obtain an opaque patch or to protect light-sensitive pharmacologically active substances dispersed in the specified patch. Cloud emulsions can be present in amounts of from 0.01% to 5% by weight, preferably from 0.1% to 3% by weight of the weight of plaster and can be selected from the group of titanium dioxide, calcium carbonate, iron oxide and bentonite clay, and talc. Preferably, the cloud is a titanium oxide.

The patch may include disintegrators, fillers and bulking agents. Salt and other low-molecular vysokodetalnye substances can also be added to facilitate dissolution. Additionally and/or alternatively, the presence of salts can influence n the osmotic process and stabilization of the patch. The presence of swelling agents and fillers in the patch may be useful to facilitate the processing and production of the patch (for example, faster drying). In addition, they can contribute to the final dissolution and the effect of the patch. The patch may contain from 0.1 to 40% by weight of swelling agents and/or fillers from the dry weight of the patch in General, preferably from 5 to 30% and more preferably from 15 to 25% by weight.

Examples of suitable swelling agents and fillers are calcium carbonate, pigments, colloidal silicon dioxide, microcrystalline cellulose, calcium phosphate, aluminum silicate and magnesium bentonite and kaolin clay.

In one of the embodiments of this invention, the pharmaceutically active substance is nicotine, and aboutgenwhy layer contains improving the taste and smell of the substance.

In one of the embodiments of the present invention biodegradable patch is sublingual patch consisting of bioadhesive layer and aboutgetting layer, and bioadhesive layer includes polyamoury dispersion and bioadhesive polymer, and poliarnaia dispersion contains a pharmacologically active substance. Preferably, the pharmacologically active substance is nicotine. In this embodiment aboutgenwhy polymer contains gelatin and improve the taste and smell of the prophetic is STV. Preferably, bioadhesive layer contains polyvinyl alcohol and/or polyvinylpyrrolidone. To place in the mouth bioadhesive layer is glued to the bottom of the sublingual cavity, so aboutgenwhy layer may contact with the lower part of the language user. This embodiment has several advantages. In particular, the product of this embodiment is durable, flexible and convenient patch. In addition, improving the taste and odor of the substance present in naviadesign.com layer, provides taste masking function. This can be especially useful when pharmacologically active substance has an unpleasant taste, such as nicotine.

It will be clear that by careful selection of polymers used in bioadhesives and naviadesign.com layers of biodegradable patch can be created so that or bioadhesives and aboutgenwhy layer is dissolved and/or dispersed with greater speed than the other layer. For example, when the patch is sublingual patch, preferably, when aboutgenwhy layer contains a specified masking or improving the taste and odor of the substance, for aboutgetting layer to dissolve and/or dispergirovanija at a slower rate than bioadhesive layer.

Biodegradable patch can contain more than one bioadhesive and/or aboutgetting words the century

The size and shape biorazlagaemykh patch will be determined by the desired use of the specified patch, for example, to dissolve in the mouth or for application to an open wound or premises in the rectum or vagina, when necessary. Suitable shapes include discs, ellipses, squares, rectangles, and parallelepipeds. The surface area aboutgetting layer is preferably larger than the surface area bioadhesive layer.

When bioadhesives and aboutgenwhy layers represent the film thickness of the device may vary depending on the thickness of each layer. Preferably, the thickness of the two layers is in the range from 0.05 to 3 mm, and more preferably, from 0.2 to 2 mm, and more preferably, between 0.3 and 1.5. The thickness of each layer may vary from 10 to 99% of the thickness of the entire device, and preferably varies from 30%to 60%.

Birthdaaay the patch, as described herein, may optionally include at least one peelable sheet, which can be presented on any of bioadhesives or aboutgetting layer or both, bioadhesives and naviadesign.com, layers. For ease of handling and for convenience it is preferable that the peelable sheet was, at least bioadhesive layer. Suitable materials for the indicated peelable layer will Ho the Osho known to specialists in this field and include, but not limited to, for example, polyethylene, polyethylene terephthalate, polypropylene, polystyrene, polyvinyl chloride and polyvinyl acetate.

Birthdaaay the patch of the present invention may be fitted with a sealed packaging to prevent damage. Suitable systems are well-known experts in this field.

One of the advantages biorazlagaemykh patch for use in cheek or sublingual delivery is that unlike absorption from the intestine, the pharmacologically active substance penetrates into the systemic circulation from the cheek cavity in the place where the blood does not pass directly through the liver (where most of it is metabolized before it has the desired effect). Elimination metabolism in the liver significantly improves the bioavailability of the pharmacologically active substances. Unlike other dosage forms-cheek delivery, such as a dry film, the quick-dissolving tablets, pellets and the like, the patch of the present invention has the advantage that bioadhesive and neibiadeeno layers may be of such composition that are soft, flexible and easy to use, at the same time having a relatively high concentration of pharmacologically active substances and, in particular, fat-soluble pharmacologists who Eski active substances, with the release in an easily absorbable form. Many of dosage forms for delivery of the cheek region, known to specialists in this area, not suitable for the delivery of membrane not easily soluble in water drug substances. Since the patch of the present invention may be held in place using bioadhesive layer pharmacologically active substance mainly will usually be lost during swallowing, and thus provides a more constant dosage.

In one of the embodiments of the present invention biodegradable patch contains bioadhesive layer, and bioadhesive layer contains the first polyamoury dispersion comprising a first pharmacologically active substance, and optionally, the second polyamoury dispersion containing additionally a second pharmacologically active substance. The first and the second pharmacologically active substance may be the same or different. In this embodiment of pharmacologically active substances can be, for example, nadolol and lorazepam (to treat anxiety), azelastin and Ketoprofen (as antihistamines for the treatment of pain), simvastatin and ezetimbe (statin in combination with an inhibitor of cholesterol intake).

In one of the embodiments of the present invention presents a wound dressing consisting of Birznieka the patch, which are described here.

In another embodiment of the present invention presents a biodegradable capsule containing biodegradable patch, which is described here. Suitable for the manufacture of biodegradable capsules substances known to specialists in this field and include, for example, HPMC (hypromellose) intersolubility coating, such as acetotartrate. As the capsule passes through the gastrointestinal system of the patient, the capsule will act as a protective coating for plaster until when the capsule will be placed in the desired position. Then, the capsule is made so that it will dissolve, disintegrate, or decompose and allow the plaster to stick to the mucosa and to deliver pharmacologically active substance, when it dissolves, disintegrates and degraded.

In accordance with this invention presents a method of manufacturing a patch, which is here defined, including the formation of polihronova dispersion containing a pharmacologically active substance; mixing the specified polihronova dispersion and bioadhesive polymer with the formation of bioadhesive layer and receive on the specified bioadhesive layer aboutgetting layer.

Bioadhesive layer can be formed by zapechatyvanie bioadhesives of the polymer or the second surface or on an existing layer.

In another aspect, presents a method of manufacturing a biodegradable patch, which is described here, including the formation of aboutgetting layer and create on the specified naviadesign.com layer bioadhesive layer, and bioadhesive layer contains polyamoury dispersion comprising pharmaceutically active substance and bioadhesive polymer.

Aboutgenwhy polymer can be molded by zapechatyvanie aboutgetting polymer or temporary surface or on an existing layer.

In one of the embodiments, when bioadhesive layer includes forming bioadhesive film polymer comprising polyamoury dispersion, bioadhesive layer can be formed by molding, film forming polymer, and let it dry. When the film becomes dry, bioadhesives the layer can be applied aboutgenwhy layer and let it dry (if aboutgenwhy layer contains a film forming polymer) or allow them to go through the Sol-gel transition (if, for example, use gelatin).

Layers can be dried, partially dried, or may be moistened before applying the second layer.

Bioadhesive and/or aboutgenwhy layer can be formed according to methods known to experts in this field, such as by printing, by immersing the film, coating film, whether the rd film, cover by centrifuging or by spraying with subsequent drying. Covering solution can be applied using several methods, including a scraper-blade, extrusion, roller, spraying, application with a brush (brush) or a thin uniform layer. The layer can be obtained on the appropriate substrate, such as a supporting surface or to an existing layer. The solution can be applied at the desired thickness and dried (if necessary) with or drying Cabinet, or, preferably, a flow of heated gas (such as air). The supporting surface may be coated paper, Mylar, or any other relevant unyielding and impenetrable substrate. Preferably, the surface of the support film in a stable dimensions during the process of coating and curing/drying, but gives you the opportunity to get free layer/adhesive (e.g., by peeling), when necessary. It may be desirable to cut the film on the substrate on the respective desired geometry, and then separating the resulting product. The solids content in the covering solution, the viscosity of the obtained solution and the thickness of the coating determines the number of the covering film, which is deposited on the forming surface./p>

In this method of manufacturing a biodegradable patch, which is defined here, can be taken appropriate steps to eliminate or reduce any degradation or loss of pharmacological tools. The person skilled in the art will be aware of the appropriate steps that can be taken. These steps may include temperature control, ambient air, pollutants and lighting. For example, the method of manufacturing a patch may require low temperature drying in a stream of inert gas with the appropriate filter, and in a darkened environment, to prevent the decomposition or contamination of pharmacological tools. Other specific factors which also need to contact, should be obvious to a person skilled in this field.

Powdered polymers can be included in the patch, or by adding on another wet or partially wet) polymer layer or completely dried adhesive layer. In the case of "wet" format excess water helps to hydrate the polymer, causing its fixation on an existing polymer layer. The level of water present is usually insufficient for complete hydration/dissolution of powdered polymer, it is sufficient only to make it stick. This system then advanced su is at. In the case of "sticky" system cast highly plasticised base coat and fully dried. Then, on this layer in excess of the applied powder, and some sticks to the base layer, due to this inherent layers of stickiness.

Additional combining (linking) polymer can be represented between bioadhesive and nabyudeniem layer. Additional combining (linking) polymer binds bioadhesives and aboutgenwhy layer together to prevent or substantially prevent separation during use.

In one of the embodiments of the present invention presents a method of using biorazlagaemykh patch, which is described here, human or animal, comprising the application of a biodegradable patch, which is described here, on the mucous membrane of a human or animal. Surface mucous include, but are not limited to, the surface of the cornea, conjunctiva, nose, cheek, sublingual, lungs, stomach, intestines, uterus, bladder, rectum and vagina. This method can be used to treat depression, drug abuse, diabetes, epilepsy, fungal infections, gout, hypertension, malaria, migraine, Parkinson's disease, cancer, viral infections, bacterial infections, eczema, local or systemic pain, elevated cholesterol levels, inflammation, the besso is nice, protozoal infections, infestations tape worms, arrhythmia, thrombosis, angina, allergic reactions, disorders of balance of thyroid hormones, psoriasis, swelling or infection of the gastrointestinal tract. Birthdaaay the patch can be placed in a specific location on the mucosal surface of the patient/mammal, for example, by hand or during the surgical intervention. Alternative or additional biodegradable patch can be placed on the mucosal surface of the patient/mammal not directly, for example through the patch of the present invention in a capsule suitable for oral administration.

In another embodiment of the present invention presents a set of parts, including:

(i) at least one bioadhesive layer, which contains at least one polyamoury dispersion comprising pharmaceutically active substance and at least one bioadhesive polymer and (ii) at least one aboutgenwhy layer.

The following additional examples illustrate the invention.

Getting polifrone

In an appropriate vessel loaded aqueous phase polihronova suspension. The oil phase is added with constant speed under stirring, using scraper mixer or orbital mixer. When you are finished adding oil is remesiana continue until when the size of the droplets of oil that is stable or reaches the desired size.

Poliarnaia variance 1% (V/V)Weight (g)
The oil phase
Soybean oil71,721,51
Cremophor RH 40 (BASF)1,00,3
Nicotinethe 17.35,19
The aqueous phase
Poloxamer 188 (10 weight. %) (BASF)
In deminer. water8,22,46
Nicotine1,80,54
10030
Poliarnaia variance 2% (V/V)Ve is (g)
The oil phase
Soybean oil79,923,97
Cremophor RH 40 (BASF)1,00,3
Nicotine9,12,73
The aqueous phase
Poloxamer 188 (10 weight. %) (BASF)
In deminer. water9,12,73
Nicotine0,90,27
10030
Poliarnaia dispersion 3% (V/V)Weight (g)
The oil phase
Soybean oil88,553,4
Vitamin Acetat 0,50,3
Span 801,00,6
The aqueous phase
Poloxamer 188 (10 weight. %) (BASF)
in deminer. water10,06,0
10060,0
Poliarnaia dispersion 4% (V/V)Weight (g)
The oil phase
Waglinol 3/928078,523,55
Lime flavoring
051.182/T10,03,0
Oleth 100,750,225
Etocas 290,750,25
The aqueous phase
Poloxamer 188 (10 weight. %)
in deminer. water10,03,0
10030
Poliarnaia variance 5% (V/V)Weight (g)
The oil phase
Soybean oil83,5525,06
Nicotine5,551,67
Sorbitol monooleate0,900,27
The aqueous phase
Poloxamer 188 (10 weight. %)
in deminer. water10,03,0
the 10030
Poliarnaia dispersion 6% (V/V)Weight (g)
The oil phase
Ibuprofen6,60,66
(-)Menthol2,20,22
Mint flavoring
T8,900,89
Cremophor RH 400,900,09
Span 800,600,06
Olive oil80,808,08
The aqueous phase
Poloxamer 188 (10 weight. %)
in deminer. water10,0 1,00
10010,00

Manufacturer bioadhesive layer

Using the appropriate vessel components bioadhesive layers are mixed in a low effort shift. Bioadhesive solutions 4 and 5 are heated to 80 degrees Celsius to facilitate dissolution of poly(vinyl alcohol).

Bioadhesive layer 4 is stirred at high shear (2000 rpm) to ensure appropriate distribution of the pigment particles.

Bioadhesive layer 6 is produced by heating to 55 degrees Celsius with stirring at low shear. This system is maintained at this temperature until use.

Bioadhesive layer 1% (V/V)Weight (g)
The solution of polyvinyl alcohol :
in Demin. water (20 wt.%)of 87.310
Poliarnaia variance 18,40,96
Glycerin4,310011,46
Bioadhesive layer 2% (V/V)Weight (g)
The solution of polyvinyl alcohol :
in Demin. water (20 wt.%)of 87.310
Poliarnaia variance 28,40,96
Glycerin4,30,50
10011,46
Bioadhesive layer 3% (V/V)Weight (g)
The solution of polyvinyl alcohol :
in Demin. water (20 wt.%)91,3091,30
Poliarnaia dispersion 38,708,70
100 11,46
Bioadhesive layer 4% (V/V)Weight (g)
Water50,8315,25
Polyvinyl alcohol :
(Golsenol EG-05, Nippon Gohsei)15,734,72
Titanium dioxide
(S-060, Suncroma)3,481,04
Sorbitol9,432,83
Sodium chloride4,711,41
Poliarnaia variance 515,824,75
10030,00
Bioadhesive layer 5% (V/V)Weight (g)
Polyvinylpyrrolidone
(Polyplasdone K32, ISP)32,359,71
Sodium chloride1,800,54
Sorbitol13,884,16
Polyvinyl alcohol :
(Golsenol EG-05)5,321,60
Water21,246,37
Poliarnaia variance 525,41a 7.62
10030,00
Bioadhesive layer 6
Polyvinylpyrrolidone K10,05,0
Xylitol5,02,5
Gelatin20,010,0
Water 56,0028,00
Food coloring0,250,12
Poliarnaia dispersion 68,75of 4.38
10050,0

Obtaining solutions aboutgetting polymer

Solutions aboutgetting polymer 1 and 5 are dissolved and mixed at low shear at 50 degrees Celsius to obtain a homogeneous mixture.

The solution aboutgetting polymer 6 is stirred at low shear at 85 degrees Celsius to obtain a homogeneous mixture. All solutions are maintained at an elevated temperature prior to use.

2,50
The solution aboutgetting polymer 1%(weight.)Weight (g)
Gelatin brands GP3030
Demin. water5555
Glycerin1515
100100
The solution aboutgetting polymer 2%(weight.)Weight (g)
Poliarnaia dispersion 3101
The solution aboutgetting polymer 1909
10010
The solution aboutgetting polymer 3%(weight.)Weight (g)
Poliarnaia dispersion 4101
The solution aboutgetting polymer 1909
10010
The solution aboutgetting polymer 4%(weight.)Weight (g)
Gelatin28,243,53
Sorbitol20,00
Water51,766,47
10012,5
The solution aboutgetting polymer 5%(weight.)Weight (g)
Gelatin24,5321,18
Sorbitol24,5321,18
Microcrystalline cellulose
(Chemfields PH101)5,795,00
Blue food coloring0,170,15
Metabisulphite sodium0,030,03
Water44,9538,82
100,0086,36
The solution aboutgetting polymer 6% (wt.) Weight (g)
k-carragenan2,00,8
Microcrystalline cellulose15,06,0
Xylitol5,02,0
Water78,031,2
10040,0

Additional layers

All additional layers were mixed manually.

An additional layer 1%(weight.)Weight (g)
Polyvinyl alcohol :
(Golsenol EG-05),
solution in Demin. water
87,768,78
Sorbitol1,730,17
Sucrose10,511,05
100,00 10,00
The additional layer 2
Powder a Noveon AA-1 (modified polyacrylic acid, a Noveon)
An extra layer 3% (wt.)Weight (g)
Sorbitol11,844,50
Xylitol11,844,50
Polyvinylpyrrolidone
(Polyplasdone K90) solution in
Demin. water 13.8% in/in (ISP Corp)
76,3229,0
100,0038,0
The additional layer 4% (wt.)Weight (g)
Pectin (Kelco)25,02,00
Gantres MS-95525,02,00
Sodium alginate (Keltone LVCR) 2,00
Modified starch
(Cargill 03302)25,02,00
100,008,00

Obtaining biodegradable patches

Biodegradable patch. Example 1

Part bioadhesive substance layer 1 was placed in a Teflon laboratory glass for the formation of a smooth thin film, which was left to dry at room temperature for 2 days with the formation of a dry film (approximately 0.3 g). Of dry film formed after drying bioadhesive layer 1, cut a circular disk (diameter about 1.5 cm). This drive had a total estimated nicotine content in General 2,69 mg. Disk was placed on corrugated metal block and covered with a small amount of solution (20% V/V) polyvinyl alcohol as a binder for the next layer. A gelatin solution (solution aboutgetting polymer 1) at 50 degrees Celsius person to distil from this disk and allowed to cool. When the sample was cooled, it was removed from the metal block and placed in wide-mouthed vessel to prevent drying of the film. The sample was presented with the battle biodegradable patch with bioadhesive layer, related nabyudeniem layer.

Biodegradable patch. Example 2

Applying the same method as in example 1, was obtained dry film of dried bioadhesive layer 2. Of dry film cut out a circular disk. This CD had a nicotine content, equal 1,80 mg On the disk was coated as described in example 1. Used a gelatin sample was a solution of 2 aboutgetting polymer. The sample was biorazlagaemykh plaster with bioadhesive layer associated with nabyudeniem layer.

Biodegradable patch. Example 3

Getting biorazlagaemykh patch of wet on wet

An alternative approach to the above using wet bioadhesive layer, and then drying the coating aboutgetting layer and leaving the film to dry in the air. The method was the following:

1. On the corresponding metal block with a width of 25 mm, notch depth of 2 mm, is evaporated bioadhesive layer 3 containing a drug substance, so that the film thickness is about 100 μm. To achieve this, use a scraper-blade, below the upper level of the notch. Location bioadhesive film is such that about 30 mm excavation not covered with finished foil.

2. Put the required amount of solution aboutgetting layer 3 in uncovered cha is to be cut. Using a scraper-blade, distribute aboutgetting film wet bioadhesives the film, so that the edge of the blade is flush with the top edge of the metal block.

3. Allow to air dry, remove the two-layer film and cut to size.

Biodegradable patch. Example 4

Not biodegradable layer 3 is poured on the polycarbonate sheet, using 1 mm applicator foil and allow to form and dry. After drying aboutgenwhy layer put an extra layer 1. Before this layer is completely dry, it pripudrivayut additional layer 2. Partial solvation of powder promotes compatibility between the layers.

Separately applied bioadhesive layer 3 on the polycarbonate base, using 300 μm film applicator, and dried. The oil content in the dry film is 29.9% of the weight. After drying cut out circles with a diameter of 1 cm, using the mirror drill.

Small circles bioadhesive layer is then applied on the powder layer with small droplets of water, which promotes adhesion. Then cut out circles with a diameter of 1.5 cm, using a drill, centered on bioadhesive film so as to form concentric disks.

Biodegradable patch. Example 5

The technique is the same as in example 4, except the rising use bioadhesive layer 4 and aboutgetting layer 4.

Biodegradable patch. Example 6

Consists of aboutgetting gelatinous layer, an additional layer of hydrated containing bioadhesive powders and comprising polaron bioadhesive layer. Bioadhesive layer 3 is applied on the polycarbonate base, using 300 μm film applicator and dried.

Aboutgenwhy layer 3 is poured, using 700 μm applicator film, polycarbonate sheet and allowed to harden, but not dry. Then put the powder mixture of Methocel 40-100 (Dow Chemicals) and Gantrez MS-955 (ISP) in a mixture of 80:20. The powder is left to hydrogenate itself from the gelatin layer and dry. On the layer Methocel/Gantrez put a small drop of a 30% solution of polyvinyl alcohol (Golsenol EG-05), which acts as a binding layer, and the pre-formed bioadhesive layer is then fixed.

Biodegradable patch. Example 7

Bioadhesive layer 5 is applied on the polycarbonate basis, using 600 μm film applicator, and dried. After drying, cut out circles with a diameter of 1 cm, using a drill.

Separately cast aboutgenwhy layer 5 on the polycarbonate sheet, using 0.8 mm applicator film, and allowed to harden and dry air. After drying on aboutgenwhy layer (<50 μm) put an extra layer 3. Then immediately put the small circles bioadhesive layer followed not izlenim deposition in excess of an additional layer 4 and allow to air dry.

After drying, the excess powder was removed with a brush. Then cut out a circle with a diameter of 1.5 cm, using a drill, centered on bioadhesive film with the formation of concentric disks.

The system has experienced two of the author's invention. Plaster containing approximately 1.5 mg of nicotine, put active/bioadhesive layer on the sublingual region of the mouth and kept in place for ten seconds, to give bioadhesive stick. After about 4 minutes of monitoring both had an increase in heart rate at rest and registered touch-like effect occurs when Smoking cigarettes. Subsequent testing system with placebo did not result in any significant physiological effects. Both reported that the patch was completely dissolved after about 7 minutes with only a minimal sense of taste of nicotine that occur during the experiment.

Biodegradable patch. Example 8

Aboutgenwhy layer 6 is applied on the polycarbonate base, using 700 μm film applicator and allow to cool for 20 minutes.

700 µm film bioadhesive layer is then applied over aboutgetting layer and allow to cool. Then cut out discs with a diameter of 1.5 cm through both layers using the mirror drill. Then put bioadhesive layer on the pre-formed floor is vinyl acetate sheet for easy storage. The patch can then be removed from the protective layer when you want to use.

1. Biodegradable adhesive containing at least one bioadhesive layer and at least one aboutgenwhy layer, and bioadhesive layer contains at least one polyamoury dispersion and at least one bioadhesive polymer, and poliarnaia dispersion contains at least one pharmacologically active agent.

2. The patch according to claim 1, where bioadhesive and/or aboutgenwhy layer contains a film forming polymer.

3. The patch according to claim 2, where the film forming polymer selected from polyacrylic acid, pullulan, polyvinylpyrrolidone, polyvinyl alcohol and mixtures thereof.

4. The patch according to claim 1, where bioadhesive polymer selected from polyacrylic acid, sodium carboxymethyl cellulose, modified starch, carboxymethylcellulose, pectin, pullulan, tragakant, hyaluronate sodium, polyvinyl alcohol and mixtures thereof.

5. The patch according to claim 1, where aboutgenwhy layer contains gelatin, acetylcellulose, acetylsalicylate and/or karraginanom gum.

6. The patch according to claim 1, where bioadhesive layer and/or aboutgenwhy layer contains a polymer that can undergo Sol-gel transition as a result of changes in temperature or structuring polymer.

ALr according to claim 1, where aboutgenwhy layer contains at least one polyamoury dispersion.

8. The patch according to claim 1, where aboutgenwhy layer contains improving the taste and odor of the substance and/or dye, and/or masking the taste of the substance, and/or disintegrator, and/or a plasticizer and/or occlusive agent.

9. The patch according to claim 1, where bioadhesive layer contains improving the taste and odor of the substance and/or dye, and/or masking the taste of the substance, and/or disintegrator, and/or a plasticizer and/or an occlusive agent, and/or enhance the penetration of the substance, and/or stimulator of salivary flow.

10. The patch according to claim 9, where it stimulates the salivary flow is citric acid.

11. The patch according to claim 1, where the pharmacologically active substance is selected from an analgesic or anti-inflammatory drugs, deworming drugs, antiarrhythmic tools, anticoagulant, antidepressant, antidiabetics, ANTIEPILEPTICS, anti-fungal drugs, protivopodagricakih tools, anti-hypertension, anti-malaria assets, migraine, means antimuskarinovoe act occurs, antineoplastic agents, Antiprotozoal drugs, antithyroid tools, anxiolytic, sedative, hypnotic, or neuroleptics, corticoste is oida, diuretics, anti-Parkinson tools, gastrointestinal funds, an antagonist of histamine H1 receptors that regulate lipid assets, angina, a treatment for thyroid cancer, nutritional agents, antipyretic, antibacterial agent, immunosuppressant, anti-viral agents, hormone of the hypothalamus or pituitary gland, hormone, prostaglandin, vaccines, suppressing cough agents, local anesthetic, immunoglobulin, antiserum, according opioid analgesic, stimulant, viral vectors for gene therapy or therapeutic mixture.

12. The patch in claim 11, where the stimulant is nicotine.

13. The patch in claim 11, where the antidiabetic agent is insulin.

14. The patch according to claim 1, containing from 0.0001% to 60% by weight of pharmacologically active substances in the calculation of the total weight of the patch.

15. The patch according to claim 1 for use in a method of therapeutic treatment of the human or animal.

16. The patch according to claim 1 for use in the treatment of depression, drug abuse, diabetes, epilepsy, fungal infections, gout, hypertension, malaria, migraine, Parkinson's disease, cancer, viral infections, bacterial infections, eczema, local or systemic pain, elevated cholesterol levels, inflammation, Besson who Itza, protozoal infections, worms, tapeworms, arrhythmia, thrombosis, angina, allergic reactions, imbalance of thyroid hormones, psoriasis, delayed excretion of fluids or gastrointestinal infections.

17. Using the patch according to claim 1 for the manufacture of a medicine for the treatment of depression, diabetes, drug addiction, epilepsy, fungal infections, gout, hypertension, malaria, migraine, Parkinson's disease, cancer, viral infections, bacterial infections, eczema, local or systemic pain, elevated cholesterol levels, inflammation, insomnia, protozoal infections, worms, tapeworms, arrhythmia, thrombosis, angina, allergic reactions, imbalance of thyroid hormones, psoriasis, delayed excretion of fluids or gastrointestinal infections.

18. A method of manufacturing a patch according to claim 1, comprising forming polihronova dispersion containing a pharmacologically active substance; mixing the specified polihronova dispersion and bioadhesive polymer with the formation of bioadhesive layer and receive on the specified bioadhesive layer aboutgetting layer.

19. A method of manufacturing a patch according to claim 1, including the formation of aboutgetting layer; and receive on the specified naviadesign.com layer bioadhesive layer, and bioadhesive layer includes polyamoury dispersion, containing a pharmacologically active substance and bioadhesive polymer.

20. The method according to p or 19, and bioadhesive layer is formed by printing, dipping film, coating film, casting film, cover by centrifuging or spraying bioadhesive polymer on a temporary surface or on an existing layer.

21. The method according to p or 19, and aboutgenwhy layer is formed by printing, dipping film, coating film, casting film or coating aboutgetting polymer on a temporary surface or on an existing layer.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a bandage for pain region processing. The bandage provides cooling and delivery of therapeutic formulations to this region. The bandage comprises a bearing carrier, an interpenetrating network of gel-type dope of polyvinyl alcohol and a cross-linking agent wherein the interpenetrating network is located in the bearing carrier, and at least one additional therapeutic agent.

EFFECT: bandage may be applicable many times on various body parts.

21 cl, 4 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a haemostatic device for blood coagulation improvement which contains a gauze base, a clay material located thereon, and also polyol, such as glycerol or similar placed on the gauze base for binding the clay material. The device for bleeding wound management comprises at least a portion of the clay material contacting to blood flowing from the wound to cause coagulation. A dressing applicable on the bleeding wound for blood coagulation improvement comprises a flexible base and a gauze base located thereon. The gauze base comprises the clay material and polyol. Ahaemostatic sponge also contains a gauze basis and a disperse system of the haemostatic material and polyol on the first base surface. The invention also refers to N-substituted monomers and polymers, methods for producing such monomers and polymers and to methods for using for various medical purposes, e.g. in medical devices. In the preferential versions, a medical device represents a stent.

EFFECT: haemostatic device improves blood coagulation.

43 cl, 1 tbl, 9 dwg, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine, namely to application of copolymer of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propansulfonic acid salt and 2-hydroxyethyl ester of propenoic acid as agent for release of active substance in composition for bandage. Invention also relates to bandages, containing at least one adipose substance and/or elastomeric matrix and at least one active substance, which also contain said copolymer.

EFFECT: active agent, included into bandage composition, is not toxic for cells, in particular, fibroblasts, and does not influence properties of cohesion, absorption or adhesion of compositions.

25 cl, 1 dwg, 10 tbl, 18 ex

Transdermal plaster // 2445123

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, particularly pharmaceutical preparations, namely: plasters for transdermal application. What is described is a transdermal plaster representing a matrix system and comprising a lining layer, a matrix layer and a lightproof protective coating in the following proportions: mexidol substance (4.59 wt %), propylene glycol 10.32 wt %, PVP K90 (Plasdone K90) 10.09 wt %, 95% ethanol 75.0 wt %. The plaster aims at the transdermal introduction of mexidol. A plaster area is 25 cm2.

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5 dwg, 1 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to surgery, and is intended for pathogenically substantiated treatment of wounds of various etiology at the first stage of wound process. Described is application in wound covering of single complex from perforated cellulose Acetobacter xylinum and biologically active ingredients, which have therapeutic effect. Into wound covering included are complex fullerene C60/Tween-80 (antioxidant), antimicrobial component, antienzymatic and haemostatic component, necrolytic component.

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4 cl, 2 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention relates to transdermal therapeutic system, which contains, at least, one easily volatile and/or thermolabile biologically active substance and/or auxiliary substance, which can be obtained by limiting on each other of, at least, three components, namely, polymer matrix layer, acceptor layer, absorbing with high speed biologically active substance and/or auxiliary substance, as well as donor-layer, which by the moment of manufacturing contains volatile and/or thermolabile biologically active substance and/or auxiliary substance. During or immediately after lamination process, donor-layer by means of migration of volatile and/or thermolabile substances combines with acceptor layer.

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12 cl, 1 tbl, 1 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, more specifically to dressing used for closure and treatment of burns, wounds of various aetiology, trophic ulcers, decubitus ulcers, etc. What is described is a bandage in which three components are used: a wound-facing nontraumatic textile layer with antiseptic butole in the concentration 0.05 mg/cm2 to 1.0 mg/cm2 in a therapeutic layer which is coated with a replaceable sorptive layer made of a nonwoven fabric and providing sorption power of the bandage within 15 g/g and 10 g/g once changed. The replaceable sorptive layer is fixed between the therapeutic and sorptive layers by means of an adhesive frame which is a third component, e.g. made of a nonwoven fabric 0.1-0.5 mm thick and 6.0-10.0 mm wide; both surfaces of the frame are coated with a therapeutic adhesive, and an outer size of the framework is equal to a length and a width of the therapeutic layer. The therapeutic layer additionally contains drugs of haemostatic, anaesthetising, antioxidant and/or wound healing action.

EFFECT: production of the sustained-action bandage with extended spectrum of antimicrobial action, improved antimicrobial activity and higher sorption power.

2 cl, 1 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to ophthalmology. The invention discloses methods for detecting release and absorption rates of pharmaceutical drugs contained in eye lenses.

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23 cl, 1 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to wound coverings with using a human cell material. Substance of the invention is integrated use for repair of wounds of different area and a volume of hydrated microbial cellulose with a stratified collagen gel, and one growth factor source is found in layers or at the interface. The growth factor sources are mesodermal and/or ectodermal cells and/or blood thrombocytes. There are offered combinations and optimal proportions of the cell material providing a high therapeutic effect of the declared wound covering. Under the invention, there are prepared biologically active wound coverings containing fibroblasts, blood thrombocytes, mesenchymal stem cells, human postnatal keratinocytes.

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37 cl, 6 ex

FIELD: medicine, pharmaceutics.

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16 cl, 11 ex

FIELD: medicine.

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EFFECT: substances inactive or low-effective percutaneously if applied in certain skin regions, particularly for a long period of time, can exhibit previously unused action ensured by slow release from the bearing material.

10 cl, 4 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and chemical-pharmaceutical industry, particularly creating an oral film drug which when taken adheres to an oral mucosa, and even if adheres is easily detached therefrom. The oral film drug has at least one agent-containing layer, and at least one surface of the oral drug has a convex portion. Said convex portion is presented in the form of at least one forms specified in cones, columns, hemispheres, truncated cones. The agent-containing layer consists of a therapeutic agent and a base.

EFFECT: preparing the oral film agent.

10 cl, 4 ex, 1 tbl, 9 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a collagenic film and a method of making said film. The film contains at least one collagenic layer. The surface of the collagenic layer is formed by a plurality of domains with predominant orientation of collagenic fibres in each domain and continuous variation of orientation of fibres from one domain to another. There are pores on the domain boundary.

EFFECT: possibility of stable formation of structures similar to natural collagen.

22 cl, 21 dwg, 13 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a therapeutic system for introduction of a pharmaceutically active substance, nonvolatile at least at room temperature, with a daily dose max. 30 mg, comprising a skin non-contact and active substance impenetrable external layer, an adjacent skin distant polymeric layer of polyisobutylene of the coating weight at least 80 g/m2, an adjoining skin contact adhesive polymeric layer of acrylate copolymers of the coating weight max. 50 g/m2, and also an active substance impenetrable protective layer (easily) removed from the skin contact layer.

EFFECT: transdermal therapeutic system has a high level of using the active ingredient and a higher dose accuracy.

18 cl, 2 ex

FIELD: medicine.

SUBSTANCE: present invention refers to medicine, more specifically to a gel composition for a medical material or a hygienic material which contains a liquid rubber ingredient having a functional group able to create cross linkages, in a molecule, and 90 weight parts or more and 1250 weight parts or less of an organic liquid ingredient in relation to 100 weight parts of the rubber ingredient with the gel composition being cross-linked.

EFFECT: composition for the medical material or the hygienic material contains a great amount of the organic liquid ingredient, has sufficient elasticity and can hold its shape.

7 cl, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine. What is described is an adhesive composition containing donepezil and a stabiliser. The stabiliser containing one or more compounds specified in a group consisting of ascorbic acid, metal salt or ester of such, isoascorbic acid or metal salt of such, ethylene-diamine-tetraacetic acid or metal salt of such, cysteine, acetylcysteine, 2-mercaptobenzimidazole, 3(2)-tert-butyl-4-hydroxyanisol, 2,6-di-tert-butyl-4-methylphenol, tetrakis[3-(3',5'-di-tert-butyl-4'-hydroxyphenyl)]propionate pentaerythrite, 3-mercapto-1,2-propanediol, tocopherol acetate, rutin, quercetin, hydroquinone, metal salt of hydroxymethansulphinic acid, metabisulphite metal salts, sulphite metal salt and thiosulphate metal salts; it is added to a layer of a pressure sensitive adhesive applied on at least one side of the substrate.

EFFECT: prepared high reliable and stable adhesive composition which inhibits formation of donepezil-related compounds in the layer of the pressure sensitive adhesive.

14 cl, 4 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine. There are described Transdermal Therapeutic Systems having a silicone adhesive layer, and a method for producing and using them.

EFFECT: transdermal therapeutic systems provide achieving a certain plasma concentration.

23 cl, 3 tbl, 4 dwg, 1 ex

FIELD: medicine.

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EFFECT: adhesive preparation have sufficient elasticity for the purpose of tracking of the skin shape, as well as shows low ability to irritate the skin and high stability.

7 cl, 5 tbl, 7 ex

FIELD: medicine.

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EFFECT: film is applicable for active ingredient delivery in a mammal's body and fast soluble while contacting with a wet surface.

18 cl, 2 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely an adhesive preparation for percutaneous introduction of 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocyclooctate[b]pyridine (compound A). The preparation contains an adhesive layer formed on one base surface wherein the adhesive layer contains (1) the compound A or its physiologically acceptable salt formed by salt addition, and (2) an acryl adhesive, or (1) the compound A or its physiologically acceptable salt formed by salt addition, (2) the acryl adhesive and (3) a permeability enhancing agent.

EFFECT: preparation inhibits metabolite generation and continuously maintains the blood drug concentration.

19 cl, 7 tbl, 1 dwg, 63 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine, particularly to ophthalmology. An oil-in-water emulsion and a method for preparing it for ophthalmic application is characterised by at least one prostaglandin as an active agent, and a surface-active ingredient containing a combination of at least two non-ionic surfactants.

EFFECT: group of inventions provides treating glaucoma and is characterised by high chemical stability of the prostaglandin active agent that enables long-term storage of the emulsion at room temperature.

30 cl, 7 tbl, 11 ex

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