Foam-forming liquid compositions containing active agents, and methods for preparing and developing thereof

FIELD: pharmacology.

SUBSTANCE: method involves preparing a liquid composition containing a pharmaceutical active ingredient, a mixture of solvents containing water, isopropanol in an amount of 5 wt % to 20 wt % and propylene glycol in an amount of 2 wt % to 25 wt %, and a phospholipid foaming agent in an amount of 2 wt % to 25 wt %, foaming the liquid composition mechanically with no propellant used, and measuring the foam volume and stability. That is followed by transforming the nature and/or changing the concentration of the pharmaceutically active ingredient and/or the phospholipid foaming agent and/or changing the concentration of one of the solvents to produce 250 ml of the liquid composition. The above liquid composition is expected to produce foam in the volume of 400 ml and with the stability so that 50% of an initial foam volume is observed so far after the 10-minute hold-up and measured by the standard SITA procedure. The invention also relates to a composition applicable for topical use and prepared by the method described above.

EFFECT: preparing the composition presented by the stable foam.

22 cl, 18 dwg, 1 tbl, 18 ex

 

This invention is directed in part on the method of obtaining or developing liquid pharmaceutical compositions applied in the form of foam on the skin, with the features of the preamble of claim 1 and corresponding topically applied compositions with the features of the preamble of claim 9.

Topically applied pharmaceutical composition, which exist in the liquid state and in the application are in the form of foam are well known. For example, in European patent document EP 0510561 B1 describes one such pharmaceutical composition is applied in the form of foam, where the main liquid used in the known pharmaceutical compositions, foamed solely by mechanical action. The main liquid composition which is foamed mechanically, contains as ingredients surfactant as a foaming tool, the solvent or mixture of solvents, as well as pharmaceutical active ingredient, where this is known liquid composition should be expanded by simple mechanical action without the use of a propellant. In example 5 of European patent document EP 0510561 B1 describes one such known composition containing water alkylaminocarbonyl solution as a surfactant. In addition, the composition described in this example is, provided with lecithin, which is used exclusively for the formation of liposomes.

To measure the pricing behavior of liquid compositions is known, various techniques for measuring and standardized, for example, according to DIN Standard 53902. The concrete investigated liquid composition has been more or less repeated mechanical action within a specified period of time for formation of the foam volume and stability of which was measured.

According to German patent document DE 19740095 AND, however, known techniques of measurement is not sufficiently varied amounts of foam and stabilnosti foam compositions that are similar to, depending on their ingredients.

Consequently, in German patent document DE 19740095 AND offer a foaming liquid composition, measured using a stirrer with a given profile, which run at a given speed of rotation. The foam formed in this way, visually measured.

Additional variant of the implementation of this technique of measuring the foam described in the European patent document EP 1092970 B1, where development is different from measuring techniques previously described in reference to German patent document DE 19740095 AND providing automatic determination of the height of foam measuring electrodes. This method of measurement, which is called the "method of measurement SITA" in question is the text allows you to determine the amount of foam on the one hand, and on the other hand the stability of the foam liquids, especially painting and cleaning solutions, electrolytic means, emulsions, means for rinsing, products for body care or even beer to obtain an estimate of the quality of the above-mentioned foaming liquids.

When it is necessary to develop fluids that are foaming and, therefore, applied in the form of foam, in the field of pharmacy, normally it is proposed to continue the choice of pharmaceutically active fluid and then try it to foam up, changing technology mechanical foaming, in particular, changes in atmospheric pressure, geometry and configuration of the nozzle to foam and valve specific applicator for foam. However, this method of development for foaming initially liquid pharmaceutical compositions is very premeditatedly and may experience a drawback is that the foam that is different in composition and significantly inhomogeneous, may result from changes to the configuration of the above-mentioned parameters of the mechanical applicator for foam.

Thus, one underlying problem of this invention is the provision of method development in liquid pharmaceutical compositions applied in the form of foam on the skin, which the development time for such Pharma is efticiency compositions greatly simplified and reduced.

In addition, another underlying problem of this invention is the provision of topically applied compositions, which can be applied as a foam and which contains systemically or topically active pharmaceutical active ingredient, whereby this topically applied composition is designed preferably the above-mentioned methods.

The first stated problem was solved by the method according to the characteristics of claim 1 and an additional problem, which is mentioned later, decided using topically applied composition with the features of the preamble of claim 9.

In the method of this invention is the development of a liquid pharmaceutical composition applied in the form of foam on the skin with a minimum of components, as a solvent, pharmaceutical active ingredient and a blowing agent, the method involves determining the amount of foam and foam stability of a standardized way of measuring SITA, this method did not use gas propellant. In the provided liquid pharmaceutical compositions, at least one foaming agent, at least one solvent and at least one pharmaceutical active ingredient has changed with regard to their chemical nature and/or concentration, while the foam formed by the method of measurement SITA when standarts the reported conditions, will not have the volume of foam at least 400 ml, especially the amount of foam from 450 to 1400 ml, and preferably the amount of foam from 600 to 1200 ml. in Addition, the foam according to the method of this invention should have such a stable foam, which it still holds after the exposure time up to ten minutes, and especially after the exposure time up to five minutes, at least 50% of the volume of foam and especially from 55% to 100% of the volume of foam and preferably from 85% to 99% of the volume of foam that originally existed directly after the formation of the foam. In other words, therefore, the way to develop this invention calls for the change of the minimum of ingredients (solvent, pharmaceutical active ingredient and a blowing agent)contained in the liquid pharmaceutical composition, which allowed for the formation of foam, when applied, depending on their chemical nature and/or their concentration as they will not lead to foam a method of measuring SITA under standardized conditions, the volume of foam which has a previously defined volume and foam stability which has previously defined stabilnosti.

The above method of the present invention has many advantages. Thus, it was found that the method of this invention makes it particularly easy and fast to develop such liquid pharmaceutical com is ositio, which can reproducibly foam up a lot of foam applicators so that in contrast to the prior art described at the beginning, it was possible to develop a pharmaceutical foam, which is particularly reproducible depending on their foamy consistency and foam compositions. For example, if the purpose of such development is the provision of a liquid composition, the foam should have a relatively short stability after foaming by means of a suitable mechanical applicator for foam so that it quickly opal after application to the skin, in the method of the present invention can be modified chemical nature and/or concentration of ingredients before the foam gives the result in the measurement of SITA, in which the stability of the foam is characterized by the fact that within two to four minutes, the volume of foam still occupies a volume of from 50% to 70% of the original volume of the foam. In contrast, when the goal is to create a stable foam, chemical nature and/or concentration of at least ingredients of the liquid composition, which subsequently form the foam will vary to produce a foam, the foam stability was so high that after eight to ten minutes was still present from 85% to 99% of the volume of the foam, which was present initially just before process canoo is education. If, on the other hand, the necessary liquid foaming composition having a particularly large amount of foam, then the nature and/or concentration of at least the liquid ingredients of the composition will vary, so that a particularly high volume of foam leads to the way of measuring SITA, i.e. the volume of foam, which varies from 600 ml to 1200 ml or 1400 ml Thus, it should be noted that the method of the present invention provides a standardized way in which changes in the chemical nature of the ingredients and/or their concentration can develop a foam as defined in the above sense, relative to the volume of foam and foam stability, and which can accordingly be applied to the skin of humans and animals.

The expression "and/or"used in this description, means that some or all items from a specific list was interpreted more, or that some or all of the elements of the list was interpreted alternative, whereas a standardized way of measuring SITA, which is used in this invention are described in detail in the beginning of the examples. Moreover, it is necessary to specify that all expressions used in the singular in this description of the invention, also include the plural form of these expressions.

The first variant of the method of the present invention to develop a liquid pharmaceutical preparations is practical composition, damage in the form of foam on the skin, suggests that it involves the formation of correlation between foam, as determined by the method of measurement SITA, and desirable pharmaceutical properties. Under desirable pharmaceutical properties implies, in particular, the transport of the active ingredient through the layers of foam and/or through the skin, i.e. the permeation and/or penetration of the skin and/or high distribution of the active ingredient and/or the resulting pharmaceutical effect. For example, to develop in the method of the present invention is that the active ingredient must quickly get to the skin surface at relatively high concentrations, will change the nature and/or concentration of ingredients in the liquid composition, foamed using the method of measurement SITA, so that the resulting foam was a relatively small amount of foam, especially the amount of foam from 450 ml to 600 ml, and the relatively low stability of the foam, especially the stability of the foam in five minutes from 55% to 70% of the volume of the foam, which was originally present immediately after the formation of foam.

In the modification of the above-mentioned variant of the method of the invention, another variant of implementation calls for the choice of applicator for foam for mechanical foaming liquid composition, the foam is formed from a liquid compositeevent applicator for foam, and the correlation is formed between the properties, especially the pharmaceutical properties of the foam formed by the applicator for foam and the volume of the foam and/or foam stability, as determined by the method of measurement SITA. This variant of the method according to the invention allows the development of foam with defined amounts of foam and stabilnosti foam, as measured using the method of measurement SITA, especially easily and quickly change the nature and/or concentration of the liquid ingredients of the pharmaceutical compositions, which are then correlated with the pen, which later was applied as a foam to the skin selected by the applicator for foam.

Especially when using the development method of this invention for foaming of the liquid composition, which has a foam density of 0.05 g/ml to 0.8 g/ml, preferably from 0.5 g/ml to 0.4 g/ml using the method SITA, found that such liquid compositions provide excellent foam that can be applied by many different designed mechanical type applicators foam.

Above several times already referred to the fact that the chemical nature and/or concentration of ingredients (solvent, a foaming agent, active ingredient) was changed in the method of the present invention to guarantee the amount of foam and foam stability, as described above, in the method development given the CSOs of the invention.

In particular, the solvent for forming the liquid composition in the method of this invention can be selected from the group comprising: water, at least one alcohol, especially at least one monovalent-trivalent alcohol, at least one polisport and mixtures of the aforementioned solvents. Of course, the choice of solvent should be sure that these solvents can irritate the skin and especially not lead to any skin irritation, so that they respectively pharmaceutically applicable. Preferred solvents are 2-propanol, propylene glycol, glycerol and polyols, whereas the expression of water includes all water systems, especially water pharmaceutical buffer systems.

In a particularly suitable embodiment of the method of this invention by itself pharmaceutical active ingredient is used as a blowing agent, so that this variant of the method of the invention is based on the fact that it contains, in addition to the solvent, only the pharmaceutical active ingredient, concentration and chemical nature of which has changed so that the volume of foam and foam stability specified in the method of the present invention and measured way SITA, guaranteed.

Alternative or additionally, modifying the way the top is the invention offers, to the foaming agent to obtain a liquid composition selected from the group consisting of surfactants, especially anionic, cationic, nonionic and impolitically surfactants, silicones, fats, fatty acids, derivatives of fatty acids, phospholipids, sugar derivatives, lipids, particularly sphingolipids and glycolipids, and mixtures and derivatives of the aforementioned substances.

In principle, a blowing means, or the active ingredient, or the above-described foaming means can be capable of providing the above-mentioned quantities of foam and foam stability as soon as the liquid composition is foamed exclusively mechanically without the use of a propellant. Preferred surfactants include fatty alkylarylsulfonate, alkylphosphate, alkylphosphate, alkyl benzosulfimide, petroleum sulfonates, the olefin sulfonates and/or esters sulfosuccinic acid. Among the silicones have to mention especially modified siloxanes, polydiorganosiloxane and, preferably, linear or cyclic polydimethylsiloxane. Fats and modified fats, such as fatty acids, derivatives of fatty acids, esters of fatty acids, synthetic, vegetable and animal phospholipids, especially phosphatidylcholine and/or hydrog is organized phospholipids and preferably gidrogenizirovannye phosphatidylcholine, are among the preferred foaming means, in addition to sphingolipids, glycolipids, and a derivative of sugar, preferably esters of sugar or sorbitol.

Among the fatty derivatives, especially sulfates of fatty acids, sulfonates of fatty acids, salts of sulfates of fatty acids, salts of sulfonates of fatty acids, Soaps and mixtures and derivatives of the aforementioned substances are particularly suitable as foaming tools for use in the method of the present invention. This is similar to alkoxysilane fatty acids and alkoxysilane derivatives of fatty acids, alkoxycarbonyl fatty alcohols, alkoxycarbonyl phenols, and mixtures and derivatives of the aforementioned substances.

In addition, the preferred foaming means of surface-active substances selected from the group comprising: alkylcarboxylic, alkyl sulphates, alkyl sulphonates, alkylaminocarbonyl, sulfates of fatty acids, phosphates of fatty acids, sulfonates of fatty acids, salts of sulfates of fatty acids, salts of sulfonates of fatty acids, amides of fatty acids, polyalkylene, tocofersolan-active agents, soap, metal soap and water, especially alkaline Soaps, such as salts of sodium, potassium and ammonium aliphatic carboxylic acids, organic amino Soaps, especially organic amine Soaps of aliphatic to Urbanovich acids, Quaternary ammonium compounds, particularly benzalkonium chloride, octadecylamine chloride, sulfonate salt, amidoamine, esters of fatty acids, preferably esters of monoglyceride, diglyceride and triglyceride, esters of fatty acids, alkoxysilane, especially ethoxylated fatty acids, alkoxysilane, especially ethoxylated derivatives of fatty acids, alkoxysilane, especially ethoxylated fatty alcohols, alkoxysilane, especially ethoxylated phenols, alkoxysilane, especially ethoxylated amides of fatty acids, mono - and dialkylacrylamide or alkylpolyglucoside, especially Coco mono-ethanolamide, Coco di of ethanolamide, Coco mono-isopropanolamide, Coco diglucoside, betaine, derivatives of betaine, preferably N-alkylbetaine, alkyl-aminopropylation, sulfobetaine, alkylsulfonates, allylglycine and alkylcarboxylic where alkilany balance each time contains, in particular, the carbon skeleton with 8-18 carbon atoms, allumination, alkylimidazole, N-substituted alkylamines followed, Azilect, N-acylcarnitines, alkanolamide, aminoxide, esters of a polyhydric alcohol, and mixtures and derivatives of the aforementioned substances.

As surface-active substances, which are likewise particularly suitable as a blowing means in the person of this invention for forming the liquid composition, will be selected substances which contain Quaternary ammonium compounds, salts of sulfone, amidoamine and mixtures thereof, and derivatives thereof.

Preferred impolitically surfactant to obtain a liquid composition will be selected from the group consisting of betaine and derivatives of betaine.

As the active ingredients used in the method of the present invention, preferably will be active ingredients, such as described in additional detail in connection with the topically applied composition according to this invention.

In addition to the often-mentioned solvent, a pharmaceutically active ingredient and a blowing means, in additional embodiments of the method according to the invention, to obtain a liquid composition which is foamed exclusively mechanically for its application has proposed, in particular, complexing agents, buffers, thickening agent, antioxidant and/or stabilizer. However, we must take into account that these aforementioned ingredients may also affect the amount of foam and foam stability, but it can be easily identified and easily and in the shortest time possible in a reproducible manner by the method of this invention.

As mentioned above, this invention also relates to topically applied composition with the features of the preamble of the formulas of the invention 9.

Topically applied composition of the present invention, which is designed preferably, but not exclusively, in accordance with the above method of the present invention contains a pharmaceutical active ingredient, a solvent, and a blowing agent. In contrast, the known liquid composition according to European patent document EP 0510561, for example, which is applied in the form of foam, topically applied composition of the present invention provides phospholipid foaming agent as a foaming agent. In addition, at least one phospholipid foaming agent, at least one solvent and at least one active ingredient in the compositions of this invention blended with each other by their chemical nature and/or their concentration, so that the composition can be mechanically emulsify exclusively without the use of additional propellant. The foam formed by the mechanical foaming during application, has a volume of foam, at least 400 ml, preferably from 450 to 1400 ml and especially the amount of foam from 600 to 1200 ml. in Addition, the composition according to this invention has such a stable foam, which foam still has after the exposure time up to ten minutes, and especially after the exposure time up to five minutes, at least 50% of the volume of foam and especially from 55% to 100%of the volume of foam and preferably from 85% to 99% of the volume of the foam, what originally existed directly after the formation of the foam, where both the above-mentioned volume of the foam, and the aforementioned stability of the foam can be measured in a standardized way to measure foam SITA. In other words, the topically applied composition of the present invention is characterized not only by the nature of their ingredients and/or their concentration, but also the foam formed from it, where the foam is defined and expressed quantitatively depending on the volume and the foam stability foam standardized way of measuring SITA.

The composition of this invention has many advantages. When the composition of the present invention is applied to the skin of a human or animal, where the expression of the skin, as already defined above, covers the mucous membranes of the mouth, nose, vagina and prepuce, the area of skin of ear and especially the inner ear, the skin of the anus and rectum, nails and eyes, especially the conjunctiva, cornea and lacrimal SAC, the foam formed from the composition of this invention has, first of all, excellent adhesion to these applications so that it could not unintentionally wipe. Moreover, the foam obtained exclusively mechanically from the liquid composition of the present invention, is by nature a homogeneous composition, and the active pharmaceutical ingredient present in this is th pins in a particularly homogeneous ultrafine distribution, so once the foam settles after application, it hyperfine distribution is held in a thin layer formed on the surface of the skin, with the result that the pharmaceutical active ingredient is transferred with a high rate of penetration and/or permeation into and/or through the skin. This, in turn, means that the active ingredient, thus applied, a high pharmaceutical effectiveness, so that if necessary, the concentration of active ingredient in the compositions of this invention can be reduced compared with conventional compositions or, alternatively, the time intervals between successive application can be continued accordingly, especially because the active ingredient forms of the stocks in the skin. Due to the fact that phospholipid foaming agent is present as a blowing agent in the compositions of the present invention, it phospholipid foaming agent has the effect of education is more rapid penetration or permeation into or through the skin, which proves the additional advantage of the compositions of this invention.

Especially when the foam formed from the composition of the present invention a method of measuring SITA, she has a density of 0.05 g/ml to 0.8 g/ml, preferably from 0.15 g/ml to 0.4 g/ml, such embodiments of compositions Dunn is th invention have the above-mentioned preferred properties in a high degree.

As already explained above for the method of the present invention, the composition according to this invention includes the solvent is mainly water, at least one alcohol, mainly of at least one multivalent-trivalent alcohol, and/or at least one polisport, and such solvents are selected, in particular, for such phospholipid foaming tools, because they contain a phospholipid and/or a phospholipid mixture, isolated from herbal ingredients, especially soy beans.

For clarity noted that the expression of phospholipid mixture or phospholipids in the above description covers all the phospholipids of vegetable origin, animal origin or synthetic origin. In particular, it includes ester phospholipids, especially phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylethanolamine, lyso-phosphatidylethanolamine, phosphatidyl series, lyso-phosphatidyl serine, phosphatidyl Inositol, lyso-phosphatidyl Inositol, phosphatidyl glycerol, diphosphatidyl glycerin and fosfatidov acids, essential phospholipids, especially choline plasmalogen and ethanol aminoplasmal and sphingosine phospholipids, especially the ceramide phosphorylcholine and phytoglycogen and ester derivatives of phospholipids, essential phospholipids and/or sphingosine phospholipids, regardless of the TRG is, will they be isolated from natural substances such as plants or plant components, especially the seeds of a plant or animal components, such as eggs, or synthetically derived. Typical derivatives of these phospholipids that may be contained in the composition of this invention as a foaming agent are preferably hydrogenated or partially hydrogenated phospholipids, especially hydrogenated or partially hydrogenated phosphatidylcholine.

With regard to the active ingredient, it should be noted that at least one active ingredient contained in the composition of the present invention, suitable for use in humans or animals, and especially for local and systemic application, especially on the skin, where it is especially preferred active ingredient is selected from the group consisting of local anesthetics, anti-allergic medicines, skin, active ingredients against flu infections and colds, active ingredients for the treatment of neuropathies, active ingredients for the treatment of circulatory disorders, drugs for chemotherapy, quinine, antifungals, antibiotics, thalidomide, serotonin, eicosanoids, analgesics, anti-convulsants, non-steroidal Antirheumatic agents, leukotrienes, inhibitors of leukocyte is Reena, androgens, antiandrogens, corticoid, antagonists of opioid receptors, inhibitory substances for blood clotting inhibitors accumulation of platelets, histamine antagonists, regulatory and enzymatic active peptides and proteins, nucleic acids (single - and double helix DNA, single and double helix RNA, snRNA, DNA oligonucleotides, RNA oligonucleotides and oligopeptides, antipruritic, anti-diabetic, prostaglandins and inhibitors of prostaglandin synthesis, antiviral active or virusstatus active substances, anti-microbial active substances, active ingredients against prion, immune suppressors, hormones, active ingredients for the treatment of warts or wounds, especially chronic wounds, vitamins, herbal extracts or essences herbal extracts, psychotropic drugs, active ingredients affect sleep, analeptics, General anesthetics, muscle relaxants, anticonvulsants, antiparkinsonian tools, antiemetic, antiparasitic, ganglion-active ingredients, simpaticeskii active ingredients, parasimpaticheskih active ingredients, proteobacterial existing drugs, calcium antagonists, cardiovascular tools, Antiasthmatic, antitussive, expectorant, acting on the liver, Dior the Tiki, haeretici, bleach, trace elements, anti-infective, cytotoxic agents, antimetabolites, hormone antagonists, immunomodulators, and derivatives and salts of the above-mentioned active ingredients.

Depending on the particular application of the composition of the present invention, the compositions of this invention comprise an active ingredient or a special blend of active ingredients selected from the following list of specific active ingredients, presents their specific major groups.

Preferably, for the main group of inhibitors of 5α-reductase, you can use alfatradiol and 17α-estradiol; for the main group means of weight loss, curb appetite or anti-obesity: norephedrine, phenylpropanol Amin, D-norpseudoephedrine, orlistat and sibutramine; for the main group of ACE-inhibitors: benazepril, cilazapril, inapril, ramipril, spirapril and trandolapril; for the main group of medicines from acidosis or antigipoksicheskim funds: calcium-sodium-hydrogen-citrate; for the main group of knitting: aluminum chloride, aluminum diacetate, aluminum formate, chloride, oxide of bismuth, gallate of bismuth, policresulen, tannin and zinc oxide; for the main group of funds from acne: azelaic acid and benzoyl peroxide; for the main group of aldosterone antagonists: canremove the acid, canrenoate potassium, dolasetron and eplerenone; for the main group of means for removing alcohol: acamprosate and disulfiram; for the main group of antagonists of α1-receptor: alfuzosin, bunazosin and digidroergotamin; for the main group of α2 agonist-receptor: apraclonidine, brimonidine, doxazosin and moxonidine; for the main group of α - and β-sympathomimetics: adrenaline, dobutamine, dopexamine and epinephrine; for the main group lipophilic antibiotics: gentamicin, kanamycin, neomycin, netilmicin, streptomycin, and tobramycin; for the main group of amino acids: alanine, aminouksusnoy acid, glycine, arginine, asparagine, aspartic acid, cysteine, cystine, glycocol, ornithine, Proline and series; for the main group substitution of amino acids: albergotti, arginine glutamate, desmoines, glycine, glutamine and glycyl tyrosine; for the main group of analeptics or protivoepidemicheskih funds: camphor and caffeine; for the main group of analgesics or anti-rheumatic funds: abatacept, acetylsalicylic acid, acetaminophen, ademethionine, anakinra, aurothiomalate sodium, buprenophine, diethylamine salicylate, etanercept, etoricoxib, fentanyl, flutamida acid, flupirtine, glucosamine, hydromorphone, 2-hydroxybenzoic acid, salt ditrapano, hydroxychloroquine, hydroxyethylacrylate, Leflunomide, levomethadone, metasin is l, Metamizole, methyl salicylate, misoprostol, morphine, nalbuphine, aurothiomalate sodium, Nicolosi, nonivamide, norepinephrin, novaminsulfon, oxaceprol, oxycodone, paracetamol, penicillamine, pethidine, Ferguson, piritramid, propylenimine, propifenazona, salazosulfapiridin, sulfasalazin, Tilidine, tramadol and ziconotide; for the main group of funds oxidation: malic acid; for the main group of antacids: almasilat, aluminum hydroxide gel, aluminum hydroxide-magnesium carbonate, aluminum phosphate, kabalikat, magaldrate, magnesium carbonate, magnesium hydroxide and magnesium trisilicate; for the main group anthelmintic: albendazole, mebendazole, niclosamide, praziquantel, Pyrantel and Parinibbana; for the main group antiallergic: kremlinology acid, lodoxamide, meketaten, mizolastine, olopatadine; for the main group Antianemic funds: calcium folinate, darbepoetin alpha, iron, iron carboxymaltose, iron(II) chloride, iron(II) fumarate, iron(II) gluconate, iron(II) succinate, iron(II) sulfate, iron glycine sulphate, iron(III) complex hydroxide and dextran complex iron(III) hydroxide and polymaltose, the complex of iron(III) hydroxide and sucrose, iron(III) complex of sodium gluconate, epoetin Alfa, epoetin beta, epoetin Zeta, erythropoietin, folic acid and methoxy-politiical-apoetite; for the main group of anti-androgens: bikalutamid, formation and cyproteron; for the main group of antiarrhythmic drugs: aymalin, amiodarone, quinidine, decimum bitartrate, flecainide, lidocaine, meksiletin, ortsiprenalin, praelium (prajamalium) bitartrate, propafenone and sotalol; for the main group of antibiotics or anti-infective: amikacin, aminosidine, paromomycin, chloramphenicol, ciprofloxacin, clindamycin, colistimethate sodium, colistin, enfuvirtide, enoxacin, Flucloxacillin, fosfomicin, fusafungine, levofloxacin, linezolid, mefloquine, metronidazole, mezlocillin, moxifloxacin, norfloxacin, ofloxacin, oxacillin, penicillin G, penicillin V, dentists, dentists-benzathine, pipemidinova acid, piperacillin, piperacillin + tazobactam, proguanil, propicillin, pyrimethamine, retapamulin, rivastigmin, roxithromycin, sulbactam, sulbactam + ampicillin, sulfadiazine, spiramycin, sultamicillin, tazobactam + piperacillin, teicoplanin, telithromycin, tigecycline and vancomycin; for the main group of funds against dementia (memory): galantamine, nicergoline, nimodipine, piracetam, pyritinol and rivastigmine; for the main group of antidepressants: agomelatine, amitriptyline, amitriptyline oxide, bupropion, citopam, clomipramine, DULOXETINE, ESCITALOPRAM, fluoxetine, fluvoxamine mapro the Yichang, mianserin, mirtazapine, nortriptyline, opipramol, paroxetine, reboxetine, sertraline, tranilcipromin, trazodone and trimipramine; for the main group antidiabetics: acarbose, exenatide, glibenclamide, gliclazide, glimepiride, glikvidon, insulinsee, isolinear two-phase, insulinaemic, insultingly, insulinglucose, human insulin, biphasic human insulin isophane, insulin isophane, insulinoma, isophane-insulin, Metformin, miglitol, nateglinide, pioglitazone, Repaglinide, rosiglitazone, sitagliptin and vildagliptin; for the main group antidotes: bis-sulfonyl propane sulfonic acid, deferasirox, deferoxamine, deferiprone, dimercapto-propanesulfonic acid, dimethylaminophenol, disodium folinate, iron hexacyanoferrate, ezerin, flumazenil, fomepizole, naloxone, sodium folinate, sodium thiosulfate, obidoxime chloride, pontenova acid, physostigmine, silibinin and Colonia chloride; for the main group antiemetic or funds from vertigo: either aprepitant, beta Gustin, domperidone, flunarizin, fosaprepitant, granisetron, ondansetron, palonosetron and tropisetron; for the main group of anti-epileptics: carbamazepine, clonazepam, diphenylhydantoin, phenytoin, dobropoljana acid, valproic acid, tosucceed, felbamate, gabapentin, potassium bromide, lacosamide, Lahm is colleagues, levetiracetam, mesuximide, oxcarbazepine, phenobarbital, primidone, polivalentna acid, rufinamide, Altium, tiagabine, topiramate, valproic acid, vigabatrin and zonisamide; for the main group of antiestrogens: clomid; for the main group hemostatic, protivopoloznostyu and other hemostatic means: aminomethylbenzoic acid, coagulation factor I human coagulation factor VIIa, coagulation factor VII (SNO), coagulation factor VIII recombinant, coagulation factor VIII human coagulation factor IX recombinant factor, coagulation factor IX human coagulation factor XIII, alpha eptacog (activated), fibrinogen, gelatin, moroctocog alpha, nonacog alpha, oktokog alpha (KSS), fitomenadion, the proteins of human plasma, plasma proteins person with bypass activity of inhibitors of factor VIII, proconvertin, Protamine hydrochloride, Transamerica acid, troxerutin; for the main group antihistamines: Antolin, azelastin, bamipine, cetirizine, chlorphenamine, chlorphenoxamine, cyproheptadine at, desloratadin, dexchlorpheniramine, dimenhydrinate, tioxaprofen, diphenhydramine, diphenylpyraline, Bastin, emedastine, epinastine, Fexofenadine, hydroxyzine, levocabastine, levocetirizine, loratadine, rupatadine, terfenadine, tripelennamine and Tripoli the Institute; for the main group of hypertensive: aliskiren, ambrisentan, amiloride + hydrochlorothiazide, hydrochlorothiazide + amiloride, bosentan, candesartan, captopril, clonidine, delapril, enalapril, enalaprilat, eprosartan, hydralazine, imidapril, indapamide, indoramin, lercanidipine, manidipine, hydrochlorothiazide methyldopa, Minoxidil, moexipril, nilvadipine, nitrendipin, sodium nitroprusside, olmesartan, prazosin, reserpine, nitrogen monoxide, sitaxentan, telmisartan, terazosin, treprostinil and urapidil; for the main group means for lowering blood sugar: diazoxide and glucagon; for the main group protivogipergonichesky funds: amazine the methyl sulfate, efedrin, dopamine, etilefrine, levarterenol, norepinephrine, midodrin, noradrenalin, oxilofrine and adrenalin; for the main group of anticoagulants: bivalirudin, certoparin sodium, dabigatran, dalteparin sodium, danaparoid sodium, drotrecogin Alfa (activated), enoxaparin sodium, fondaparinux, heparin, heparin (low molecular weight), nadroparin calcium, reviparin sodium, Tinzaparin sodium, lepirudin, nadroparin calcium, pentosanpolysulfate sodium, protein, reviparin sodium, rivaroxaban, Tinzaparin sodium and warfarin; for the main group of antifungal: amorolfine, amphotericin b, anidulafungin, bifonazole, caspofungin, ciclopirox, cotrimazole, econazole, fenticonazole, FL is konazol, flucytosine, griseofulvin, primidone, isoconazole, Itraconazole, ketoconazole, micafungin, miconazole, naftifine, natamycin, nystatin, oscillator, Posaconazole, sertaconazole, terbinafine, tioconazole, tolnaftate, undecylenoyl acid and voriconazole; for the main group of anticancer agents: alemtuzumab, alitretinoin, bevacizumab, arsenic trioxide, asparaginase, bexarotene, buserelin, celecoxib, cetuximab and colaspis; for the main group antiparasitic funds: allethrin 1, acetic acid, permethrin and piperonylbutoxide; for the main group of anti-inflammatory drugs: Austin, ammonium bituminouscoal, ammonium bituminouscoal bright, benzydamine, bufexamac, coumarin, dimethylsulfoxide, guaiazulene, sodium bituminouscoal and serrapeptase; for the main group antipruritic: crotamiton, levomenthol, menthol and coal tar; for the main group protivopolozhnyh funds: acitretin, dimethylfumarate and ethylhydrocupreine; for the main group of antipsychotics: aripiprazole; for the main group of antiseptics: ethacridine, ethanol, denatured ethanol, fenchone, glyoxal, hexetidine, hydroxyquinoline solution sulfate, potassium thiocyanate, methenamine-silver nitrate 1:2, Phenoxyethanol, ionic silver and colloidal silver; for the main group protivochesotocnaya funds: benzyl benzoate; the La main group or antitussive salt: anethole, benproperine, cineole, codeine, dextromethorphan, Dihydrocodeine, dropropizine, eucalyptol, guaifenesin, guaiacol glycerin ether, levodropropizine, narcotine, sodium dibuat, noscapine, pentoxyverine, thymol and tyloxapol; for the main group of anticoagulants: argatroban; for the main group of anxiety: buspirone; for the main group of funds reduces appetite: amfepramone and Katin; for the main group of aromatase inhibitors: anastrozole, exemestane and letrozole; for the main group of funds from arteriosclerosis: dodecyltriethoxysilane polyoxypropylene; for the main group balneotherapy and thermal therapeutic tools: humic acid; for the main group of β-lactam antibiotics: aztreonam, imipenem, cilastatin, doripenem, ertapenem, loracarbef, Meropenem; for the main group of blockers, beta-receptor and calcium channels and system inhibitors of the renin-angiotensin-aldosterone: acebutolol, atenolol, bisoprolol, betaxolol, bupranolol, carteolol, celiprolol, esmolol, fosinopril, gallopamil, irbesartan, levobunolol, lisinopril, losartan, metipranolol, metoprolol, nebivolol, nifedipine, nisoldipine, oxprenolol, penbutolol, perindopril, pindolol, propranolol, talinolol, valsartan and verapamil for the main group of bisphosphonates: alendronate, alendronate acid, clodronate, KLO is Renova acid, etidronate, heteronomy acid; for the main group of broad-spectrum penicillin steps: amoxicillin and ampicillin; for the main group of broad-spectrum penicillin steps + of inhibitors of β-lactamase: clavulanic acid and sulbactam; for the main group of bronchodilators: aminophylline and bambuterol; for the main group of broncholytics or anti-asthmatic medications: carbocisteine, ciclesonide, clenbuterol, fenoterol, formoterol, ipratropium bromide, ketotifen, montelukast, omalizumab, reproterol, salbutamol, salmeterol, terbutaline, theophylline, theophylline the contrary, Tiotropium bromide and tulobuterol; for the main group of calcium channel blockers: amlodipine, diltiazem, felodipine and isradipine; for the main group of funds the replacement of calcium: calcium aminoethylphosphonic, calcium aspartate, calcium bis(hydrogen aspartate), calcium chloride, calcium citrate, calcium gluconate, calcium Bogoroditsa, calcium Bogoroditsa, calcium lactobionate, calcium lactogluconate and calcium salts; for the main group of inhibitors carbage[d]times: acetazolamide, brinzolamide and dorzolamide; for the main group of a cephalosporin: cefaclor, cephalo-Smoking, cephalexin, Cefazolin, cefepime, cefixime, Cefotaxime, cefotiam, cefpodoxime, ceftazidime, ceftibuten, Ceftriaxone, cefuroxime and ceph; for the main group chemotherapeutic agents: cotrimoxazole, Dapsone, nifuratel, nitrofural, nitrofurantoin, nitrofurazone, nitroxoline, actinidin, pentamidine, sulfamethoxazol, taurolidine and trimethoprim; for the main group choleretic and therapeutics for bile duct: Menton, α-pinene, β-pinene and ursodeoxycholic acid; for the main group of cholinergic funds: acetylcholine chloride, carbachol, distigmine bromide, neostigmine and mestinon bromide; for the main group of corticoids: fludrocortisone for the main group of depot penicillin: penicillin-benzathine and penicillin-procaine; for the main group of skin means: ammonium dodecyl sulphate, betakaroten, DFMO, eflornithine deformational, dodecylbenzenesulfonic acid, salt of nitrilotriethanol, ectoin, estradiol benzoate, ethyl linoleate, framycetin, guidikova acid, synthetic tannin, from sulphonated polycondensate phenol-matinale-urea, urea, hexamethylenetetramine, hydroquinone, isotretinoin, potassium hydroxide, keratin, copper(II) nitrate, lithium succinate, methane teline bromide, methenamine, methoxypsoralen, mupirocin, nadifloxacin, pimecrolimus, podophyllotoxin, salicylic acid, nitric acid, selenium disulfide, sulfadiazine-silver, tacalcitol, tretinoin and tyrothricin; for the main group of disinfectants: aminopropyldimethylamine diamine, kokopele diamine, d is desipapa diamine, ethylene deoxygenator and triclosan; for the main group of disinfectants or antiseptics: etakridin, aluminum acetate, tartrate, amylmetacresol, Bibracte, benzalkonium chloride, benzene chloride, benzyl alcohol, bishydroxyethyl urea, biphenyl-2-ol, bremgarten, pyridinium chloride, 8-hinolinol sulfate, kliohinol, didecyldimethylammonium chloride, didecyldimethylammonium propionate, hinolinol sulfate, potassium sulfate, chlorhexidine, chlorohydroquinone acid, klonopin, kokopele diamine of guanidine acetate, decaline chloride, dibromohydroquinone sulfonic acid, dichlorobenzoyl alcohol, dithranol, ethylhexanol, formaldehyde, glycoprotein, glutaral, magnesium monoperoxyphthalate, maceroni the ethyl sulfate oligodeoxyribonucleotides, ortho-phthalaldehyde, peracetic acid, polihexanide, povidone iodine, 1-propanol, 2-propanol, tetradecahydrocyclopenta, tosylchloramide sodium and hydrogen peroxide; for the main group of distortion: chlorophyllin; for the main group diet or food additives: methyloxazolidine acid, mediacoverage acid (3), mediacoverage acid (4) and oxopentanoate acid; for the main group of diagnostic tools and means for the preparation of diagnoses: aminolevulinate acid, aminal velinova acid, 5-amino-oxopentanoate acid, ceruletide, corticorelin man, iron oxide, ferumoxytol, fluorescein, gadobenate acid, gadobutrol, gadodiamide, gadofosveset, gabapentina acid, gadoteridol, halotherapy acid, gadoksetovaya acid, galactose,13C-urea, sexylatinasporno, indocyanine green, mangafodipir, palmitic acid, patent blue V, perflutren, polyvinyl chloride, protirelin, secretin, starch hydrolyzate, somatorelin, TRH (thyrotropin-releasing hormone) and tuberculin, purified for human use; for the main group of direct parasympathomimetics: bethanechol; for the main group of diuretics: bumetanide, furosemide, piretanide, spironolactone, torsemide, triamterene, triamterene + hydrochlorothiazide and xipamide; for the main group dopamine agonists: α-dihydroergocryptine; for the main group of funds, activating circulation: alprostadil, Cinnarizine, moxaverine, naftidrofuryl, peptoniphilus, prostaglandin E1 and ksantinola nicotinate; for the main group replacement of iron: ammonium iron sulfate; for the main group vomit: apomorphine; for the main group means for deducing / tools for the treatment of diseases of addiction: naltrexone, nicotine and varenicline; for the main group enzyme substituting therapy for the syndrome Fabry: agalsidase alpha and agalsidase beta; for the main group of inhibitors of the enzyme, products with a lack of enzymes and transport proteins: karpunova acid, L-carnitine, l-carnitine, an inhibitor of C1-esterase, galsulfase, hyaluronidase, idursulfase, imiglucerase, laronidase and miglustat; for the main group enzyme substituting therapy in diseases of the Pump: alglucosidase alpha; for the main group of estrogens: estriol, conjugated estrogens and ethinyl estradiol; for the main group of fibrinolitikov: alteplase, reteplase, streptokinase, tenecteplase and urokinase; for the main group of funds that make up the film: carbomer, carmellose; for the main group of solvents gall stone: chenodesoxycholic acid; for the main group of gestagens: dienoguest, drospirenone, dydrogesterone, gestodene, hydroxyprogesterone caproate, levonorgestrel, medrogestone, medroxyprogesterone, magistralata, norelgestromin, norethisterone, progestinas and D-norgestrel; for the main group treatment glacouma: bimatoprost and latanoprost; for the main group geriatrics: potassium metabisulfite; for the main group antipodagriceski funds: probenecid; for the main group of glucocorticoids: alclometasone, anyone, beclomethasone, betamethasone, budesonide, clobetasol, clobetasone, clocortolone, cloprednol, deflazacort, desoximetasone, dexamethasone, diflorasone, diflucortolone, flumetazon, flunisolide, Fluor nolinaceae, fluocinonide, fluocortolone, formation, flupredniden, fluticasone, halobetasol, hydrocortisone, hydrocortisone aceponate, hydrocortisone acetate, hydrocortisone-17-butyrate, hydrocortisone hydrogen succinate, methylprednisolone, mometasone, prednicarbate, prednisolone, prednisone, rimexolone, triamcinolone, triamcinolone acetonide, triamcinolone-16,21-diacetate and triamcinolone hexacetonide; for the main group of inhibitors of gonadorelin: cetrorelix; for the main group of gynecological tools: gemeprost, copper, metergoline, methylergometrine, lactic acid, nonoxynol, progesterone, prostaglandin E2, chinagrid and sulprostone; for the main group of hematopoietic growth factors: becaplermin; for the main group of hemostatic means: oxidized regenerated cellulose, desmopressin and collagen; for the main group acting on the liver: acetylation, betaine potassium dihydrogen citrate, choline hydrogen tartrate, complex potassium-iron-phosphate-citrate, ornithine aspartate and zinc acetate; for the main group of cardiovision (Digitalis lanata): β-acetyldigoxin, digitoxin and digoxin; for the main group means artificial hyperemia: benzylsuccinic and isobutylacetate; for the main group of hypnotic or sedative drugs: brotizolam, chloralhydrate, clomethiazole, doxylamine, flunitrazepam, flurazepam, Loreta EPAM, melatonin, midazolam, nitrazepam, temazepam, zaleplon, zolpidem and zopiclone; for the main group of hormones of the pituitary and hypothalamus, and other regulatory peptides and their inhibitors: carbetocin, hCG stimulation of alpha, chorionic gonadotropin, tetrakozaktid, β-1-24-corticotropin, follitropin Alfa, follitropin beta, ganirelix, gonadorelin, human chorionic gonadotropin, gonadotropin geofizicheskii, menotropin, lanreotide, LH-RH, lutropin alpha, mecatherm, nafarelin, octreotide, oxytocin, somatostatin, growth hormone, terlipressin, thyrotropin, urofollitropin, wagontrain and human growth hormone; for the main group of immunomodulators: eculizumab, glatiramer, lenalidomide, lenograstim, palivizumab and pegvisomant; for the main group of immune stimulants: aldesleukin, depanelization, filgrastim, inosine, interferon alpha-2A, interferon alpha-2b, interferon beta-1°, interferon beta-1b, interferon gamma-1b, pegfilgrastim, peginterferon Alfa-2A and peginterferon Alfa-2b; for the main group of immunosuppressive drugs: adalimumab, azathioprine, basiliximab, cyclosporine, cladribine, cyclosporine, daclizumab, efalizumab, everolimus, anti-human-T-cell immunoglobulin G rabbit, infliximab, muromonab-CD3, mycophenolate mofetil, mycophenolate acid, natalizumab, sirolimus, tacrolimus, and tocilizumab; for the main group the solutions for infusion or standard injections or solutions for perfusion of organs: N-acetyltyrosine, gelatin poliakine, glucose, glutamine, glycerol potassium dihydrogen phosphate, human albumin, potassium hydrogen glutamate, mannitol, sodium aminoacylation phosphate, sodium chloride, sodium hydrogen carbonate, oleic acid, 2-oxoglutaric acid, polyhydroxyethyl, hydrochloric acid, taurine, trometamol and xylitol; for the main group inhalation drugs: desflurane, dinitrogen monoxide and isoflurane; for the main group of intestinal anti-inflammatory drugs: 5-aminosalicylic acid, mesalazine, (-)-α-bisabolol, levomenol, bromelain and choline stearate; for the main group of funds, potassium replacement potassium acetate, potassium chloride, potassium hydrogen aspartate, potassium hydrogen carbonate, potassium lactate and potassium malate; for the main group of potassium-sparing diuretics: amiloride; for the main group of means to seal the capillaries: calcium dobezilata; for the main group heart drugs: enoximone, icatibant, β-methyldigoxin, metildigoxin, milrinone and oubain; for the main group of funds from caries and parodontosis and other tools for teeth: dictateur, sodium fluoride and olaflur; for the main group carminative funds: dimethylpolysiloxane and Dimethicone; for the main group of coronary drugs: ivabradine and molsidomin; for the main group of laxatives: Bisacodyl, glycerin, glycerin, lactulose, who grogol, magnesium peroxide, sodium dioctylsulfosuccinate, sodium laurilsulfate, sodium monosodium phosphate, sodium picosulfate, sodium sulfate, syrupy paraffin, polyethylene glycol and paraffin on the basis of white vaseline oil; for the main group sunscreen funds: actinoquinol; for the main group of drugs that lower lipid: atorvastatin, bezafibrat, cholestyramine, cholestyramine, etofibrate, etofillin clofibrate, ezetimibe, fenofibrate, fluvastatin, gemfibrozil, lovastatin, magnesium pyridoxal phosphate glutamate, nicotinic acid, ethyl ester omega-3-acid, pravastatin, and simvastatin; for the main group of local anesthetics or treating nervous system: AutoForm, ethyl ester of p-aminobenzoic acid, articaine, benzocaine, bupivacaine, kartikay, chlorate, cinchocaine, ethylchloride, telepresent, macrogol lauric ether, mepivacain, prilocaine, procaine, proxymetacaine, hinigaran, ropivacaine and tetracaine; for the main group gastrointestinal funds: hydrotalcite, lansoprazole, loperamide, methylnaltrexone bromide, metoclopramide, sodium alginate, olsalazine, omeprazole, oxetacaine, powder for pancreas, Pancreatin, pantoprazole, pepsin, pirenzepine, polymethylsiloxane, rabeprazole, racecadotril, ranitidine, silicon dioxide, simethicone, sucralfate, smectite, t is NIN-protein, tilactase; for the main group means substitution of magnesium: magnesium chloride, magnesium salts and magnesium sulfate; for the main group of macrolide antibiotics: azithromycin, bacitracin, clarithromycin, daptomycin and erythromycin; for the main group of anti-migraine: almotriptan, eletriptan, ergotamine, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan; for the main group of mineral drugs: calcium lactate, saharat calcium, iron, hydrogen aspartate, potassium aminoethylphosphonic, potassium citrate, magnesium aminoethylphosphonic, magnesium aspartate, magnesium bis(vodorodozapra), magnesium citrate, magnesium gluconate, magnesium hydrogen citrate, magnesium hydrogen glutamate, magnesium hydrogen phosphate, magnesium orotate and magnesium oxide; for the main group means for the treatment of homocystinuria: betaine; for the main group means for the treatment of scleroderma and induration of the penis fibroplastic: 4-aminobenzoic acid; for the main group mucolytics are presented: acetylcysteine; for the main group mucolytics are presented: desoksiribonukleaza and dornase Alfa; for the main group depolarizing and non-depolarizing muscle relaxants: alkenone chloride, atricure besilate, quinine, tsistrakuriya besilate, dantrolene, mevacore chloride, orphenadrine, pancuronium bromide, pridinol, rocuronium bromide, succinyl choline chloride, suksametonia chloride, sugammadex tetrazepam, Titanic is h, tolperison and vecuronium bromide; for the main group of metapolitical: baclofen and Methocarbamol; for the main group for narcosis: esketamine, etomidate, hydroxipropionic acid, ketamine, propofol, Remifentanil, sevoflurane, Sufentanil and thiopental sodium; for the main group of neuroleptics: amisulpride, authentiation, Potiphar, benperidol, bromperidol, butyrophenone, chlorprothixene, clozapine, difenilbutilpiperidina, droperidol, fluspirilene, pimozide, flupentixol, fluphenazine, levomepromazine and melperone; for the main group of neuropathic drugs and other neurotropic drugs: cytidine phosphate And lipanova acid, thioctic acid pregabalin, riluzole and uridine phosphate; for the main group of nonsteroidal anti-inflammatory drugs: flurbiprofen, Ketorolac-trometamol, lornoxicam, parecoxib; for the main group of nonsteroidal Antirheumatic means: aceclofenac, acemetacin, alizapride, chloroquine, dexibuprofen, diclofenac, etofenamate, ibuprofen, indomethacin, Ketoprofen, meloxicam, nabumetone, naproxen, phenylbutazone, piroxicam, proglumetacin and tiaprofenic acid; for the main group of eye means: chondroitin sulfate, gramicidin, hydroxypropyl-guar, hypromellose, hypromellose, inosine phosphate, lomefloxacin, methylhydroxypropyl the vine, the nafazolina, nedocromil, oxybuprocaine, pegaptanib, pilocarpine, polymyxin B, poly(vinyl alcohol), povidone, ranibizumab, scopolamine, sulfacetamide, tafluprost, tetryzoline, timolol, travoprost, Tropicamide, verteporfin and alcohols wool wax; for the main group of regulators osteoporosis/calcium/bone metabolism: alfacalcidol, calcitonin, disodium fjortoft, eptotermin alpha, hydroxycholecalciferol, ibandronic acid, ibandronic acid, pamidronate, panikanova acid, human parathyroid hormone, paricalcitol, raloxifene, distance the ranelate, risedronate, risedronate acid, teriparatide, tiludronate, trojanova acid, zoledronate, zoledronicaa acid; for the main group otological funds: docusinate-sodium; for the main group parkinsonism medicines and other means of extrapyramidal disorders: benserazide, parlodel, budipine, cabergoline, carbidopa, entacapone, levodopa, lisuride, meteksan, pergolid, piribedil, pramipexol, procyclidine, rasagiline, ropinirole, rotigotine, selegiline, tetrabenazine, tiaprid, tolkapon and trihexyphenidyl; for the main group of penicillins: penicillin and dicloxacillin; for the main group of phosphate binders: argentat, hydrated alumina, calcium acetate and calcium carbonate; for the main group is s means, replacement phosphate: sodium glycyrrhizinate; for the main group of photosensitizers: emodin and methoxsalen; for the main group of polyaromatic retinoids: adapalene; for the main group progestogenic funds: desogestrel and etonogestrel; for the main group of protease inhibitors: atazanavir and lopinavir; for the main group of proteinase inhibitors: antithrombin III; for the main group of protozoan funds: artemether and lumefantrine; for the main group of Psychoanaleptics: Atomoxetine, metamfepramone and methylphenidate; for the main group psychic tools: deanol; for the main group of psychopharmacological agents: doxepin, haloperidol, imipramine, lithium salts, lorazepam, medazepama, memantine, moclobemide, modafinil, olanzapine, oxazepam, paliperidone, persin, perphenazine, phenothiazines, pimozide, pipamperone, diazepam, promethazine, prothipendyl, quetiapine, risperidone, sertindole, sulpiride, thioridazine, Tikkanen, venlafaxine, ziprasidone, zotepine and zuclopenthixol; for the main group sinologicheskoj or sinusiti funds: salt Asera, synthetic salt Asera, natural sea salt, Oxymetazoline, protargol acetyl tannat, tramazoline, xanthan gum and Xylometazoline; for the main group of firming or toning: iron(III) citrate and glutamic acid; for the main group of roentgenol strastnyh funds: amidotrizoate acid, barium sulfate, diatrizoate, iobitridol, iodixanol, iohexol, iomeprol, iopamidol, iopromide yasargil, iotrolan, Strokova acid, yokagawa acid and ioxitalamic acid; for the main group of saluretics: semitized, bendroflumethiazide, chlorthalidone, clopamide, hydrochlorothiazide, hydrochlorothiazide + amiloride, hydrochlorothiazide + triamterene and mefruside; for the main group of therapeutic agents for thyroid: cinacalcet, potassium iodide, levothyroxine, liotironin, sodium iodide, sodium perchlorate, propylthiouracil, thiouracil and L-thyroxine; for the main group of essential amino acids: histidine, isoleucine, leucine, lysine, phenylalanine, threonine, tryptophan, tyrosine and valine; for the main group of secretolytic: Ambroxol and Bromhexine; for the main group of sera, immunoglobulins and inoculation: immunoglobulin (anti-D), immunoglobulin (botulism), immunoglobulin (cytomegalic inclusion disease), immune globulin (hepatitis b), immunoglobulin (human), immunoglobulin (tetanus), immunoglobulin (rabies) and immunoglobulin (varicella-zoster); for the main group of sex hormones and their inhibitors: estradiol, estradiol valerate, mestranol, mifepristone, prasterone, testosterone and tibolone; the main group of antispasmodics or anticholinergics: atropine, atropine sulfate, biperiden, bornapril, borneol, Butyrskaya is in bromide, camphene, cyclopentolate, darifenacin, glycopyrrolate bromide, hymecromone, hyoscine butylbromide, mebeverine and pipenzolate bromide; for the main group of trace elements: bis(L-histidinate)zinc, chromium chloride, chromium hydrogen aspartate, cobalt hydrogen aspartate, iron(III) chloride, copper(II) chloride, copper(II) hydrogen aspartate, manganese(II) chloride, manganese(II) hydrogen aspartate, sodium molybdate, sodium Selenite, zinc aspartate, zinc BIODROGA aspartate, zinc chloride, zinc gluconate, zinc histidine, zinc orotate and zinc sulfate; for the main group means substitution: disodium hydrogen citrate, magnesium acetate, sodium acetate, sodium hydroxide and sodium lactate; for the main group of sympathomimetics: dipivefrin and ephedrine; for the main group of tetracyclines: chlortetracycline, demeclocycline, doxycycline, meclocycline, minocycline, oxytetracycline and tetracycline; for the main group of inhibitors of coagulation of platelets: abciximab, Cilostazol, clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban; for the main group of thyreostatics: carbimazole, methimazole and tiamazol; for the main group of tocolytics: atosiban; for the main group of medicines from toxoplasmosis, Pneumocystis pneumonia and pneumonia: atovaquone; for the main group of tranquilizers (benzodiazepine): alprazolam, bromazepam, chlordiazepoxide, clobazam, diazepam and dicale clorazepate; for the main group of TB medicines: aminosalicylic acid, ethambutol, isoniazid, protionamide, pyrazinamide, rifampicin and terizidone; for the main group of drugs for ulcers: bismuth nitrate, bismuth tetraoctylammonium, cimetidine, esomeprazole and famotidine; for the main group means ortostatic: allopurinol and benzbromarone; for the main group of urological funds: dutasteride, fesoterodine, finasteride, flavoxate, potassium aminobenzoate, potassium sodium hydrogen citrate, lanthanum(III) carbonate, mercaptamine, methionine, oxybutinin, phenoxybenzamine, phytosterols, polystyrene divinylbenzene sulfonic acid, polystyrene sulfonic acid, propiverine, propyl-4-hydroxybenzoate, sevelamer, solifenacin, tamsulosin, tiopronin, tolterodine, tropia chloride and yohimbine; for the main group funds for cancer: dinoprostone; for the main group of vasodilators: adenosine, buflomedil, carvedilol, catergory, dihydralazine, dihydroergotoxine, dipyridamole, glycerol trinitrate, the isosorbide dinitrate treatment, isosorbide Mononitrate, nitroglycerin, pentaerythritol TETRANITRATE, sildenafil, tadalafil, trapidil and vardenafil; for the main group of venous drugs: heparinoid, esters of mucopolysaccharides and polimernoi acid, oligo(On-sulfo)rutozid, polidocanol, rutin and rutozid; OS the ESD group means for strengthening veins: diosmin; for the main group virostatics funds: abacavir, acyclovir, adefovir, amantadine, brivudin, cidofovir, darunavir, didanosine, efavirenz, emtricitabine, entecavir, etravirine, famciclovir, fosamprenavir, ganciclovir, idoxuridine, imiqimod, indinavir, interferon, lamivudine, maraviroc, nelfinavir, nevirapine, oseltamivir, raltegravir, ribavirin, ritonavir, saquinavir, stavudine, telbivudine, tenofovir tipranavir, trifluralin, tromantadine, valacyclovir, valganciclovir, zanamivir and zidovudine; for the main group of vitamins: aneurine, ascorbic acid, benfotiamine, Biotin, calciferol, ergocalciferol, calciferol, calcipotriol, calcitriol, calcium Pantothenate, cholecalciferol, cyanocobalamin, dihydrotachysterol, hydroxocobalamin, purified silicon dioxide, sodium ascorbate, sodium Pantothenate, nicotinamide, nicotinic acid amide, pyridoxine, retinol, Riboflavin, thiamine, thiamine divodurum phosphate-divodurum phosphate (salt of ester), thiamine disulfide, thiamine nitrate, α-tocopherol, RRR-α-tocopherol, α-tocopherol acetate, RRR-α-tocopherol acetate, DL-α-Tocopheryl hydrogen succinate, RRR-α-Tocopheryl hydrogen succinate, vitamin a vitamin-A-acid, vitamin b1, vitamin b2, vitamin b6, vitamin b12, vitamin C, vitamin D2vitamin D3, vitamin E and vitamin K1 ; for the main group of the treatment of wounds and scars: allantoin, calcium alginate, dexpanthenol, ethylcyanoacrylate, copolymers of lactide-caprolactone, poly(butylmethacrylate-co-methyl methacrylate) (x:y), polyurethane and titanium dioxide; for the main group of funds, oxidizing urine: ammonium chloride; for the main group cytoreductive funds: anagrelide; for the main group of drugs, other antineoplastic tools and bandages: adriamycin, amethopterin, bendamustine, bleomycin, bortezomib, busulfan, capecitabine, carboplatin, CCNU, lomustin, chlorambucil, cisplatin, cyclophosphamide, cytarabine, dacarbazine, dasatinib, daunorubicin, dexrazoxane, docetaxel, doxorubicin, epirubicin, erlotinib, estramustine, etoposide, fludarabine, fluorouracil, flutamide, 5-FU, fulvestrant, gemcitabine, goserelin, hydroxycarbamide, ibritumomab, idarubitsin, ifosfamide, imatinib, irinotecan, lapatinib, leuprorelin, melphalan, mercaptopurine, mesna, methotrexate, methylaminoethanol, miltefosine, mitomycin, mitotane, mitoxantrone, nelarabine, nilotinib, nimustine, oxaliplatin, paclitaxel, palifermin, panitumumab, pegaspargase, pemetrexed, porfimer-sodium, procarbazine, rasburicase, rituximab, sorafenib sunitinib, tamoxifen, tegafur], temozolomide, temsirolimus, thiotepa, tioguanin, topotecan, toremifene, trabectedin, trust is zumab, treosulfan, triptorelin, trofosfamide, uracil, vinblastine, vincristine, vindesine and vinorelbine; for the main group of biomaterials or medical plastics or various materials such as hydroxylapatite, methyl methacrylate, poly(methyl acrylate-co-methyl methacrylate) (x:y), tricalcium bisphosphate and zirconium(IV) oxide as a special active ingredient or mixture of active ingredients.

Particularly suitable variant of implementation of the compositions of this invention suggests that this variant implementation of the composition of this invention contains as active ingredient an analgesic, especially analgesic selected from the above-mentioned special analgesics, and the concentration of this analgesic in the liquid composition, which is mechanically expanded, changed, in particular, from 0.1 wt.% up to 20 wt.%, preferably in a concentration of from 2 wt.% up to 10 wt.%.

If the composition of the present invention will be applied in the form of foam for the treatment of fungal infections, it includes as a pharmaceutically active ingredient, at least one antifungal agent, especially antifungal agent, which is selected from the above-mentioned specific antifungal agents. Preferably this antifungal agent is selected from the group consisting of clotrimazole, bifonazole, econazole, fenticonazole, isoconazole, oxyco the azole, sertaconazole, tioconazole, terbinafine, miconazole, ketoconazole, Itraconazole, fluconazole, voriconazole, and derivatives of the aforementioned substances. In particular, the concentration of the antifungal active ingredient varies from 0.01 wt.% up to 10 wt.%, especially from 0.2 wt.% up to 5 wt.%, depending on the liquid composition, which is solely mechanical foam during application. The foam obtained solely by mechanical way of such liquid compositions during his deposition may then be used, in particular, with a very high pharmaceutical efficiency for fungal infections on the nails and foot and yeast infections, high pharmaceutical efficacy was shown that these fungal infections decreased after only a few applications and also better for a short time after repeating the application.

Another variant implementation of the compositions according to this invention includes as an active ingredient, at least one corticoid active ingredient, especially corticoides an active ingredient selected from the above-mentioned special corticoid active ingredients, where corticoides active ingredient is preferably selected from the group consisting of glucocorticoids, mineral corticoids and their derivatives. Depending on the specific corticoide what about the active ingredient, contained in the composition of the present invention, the concentration of this corticoides active ingredient varies from 0.001 wt.% up to 3 wt.%, preferably from 0.1 wt.% to 0.8 wt.%.

The preferred glucocorticoid selected from the group consisting of clobetasol-17-propionate, diflucortolone-21-valerate, amcinonide, betamethasone-17,21-dipropionate, betamethasone-17-valerate, destination, diflucortolone-21-valerate, fluotsinolon acetonide, fluocinonide, fluocortolone, fluprednidene-21-acetate, fluticasone-17-propionate, halcinonide, hydrocortisone-21-acetate-17-propionate, hydrocortisone-17-butyrate-21-propionate, hydrocortisone-17-butyrate, metilprednisolona, mometazon, mometasone furoate, prednicarbate, triamcinolone, clobetasone butyrate, clocortolone-21 pivalate, fluocortin, flumetazon-21 pivalate, hydrocortisone and derivatives of the aforementioned substances.

Another variant implementation of the compositions according to this invention provides that the composition of this invention contains as an active ingredient, at least one local anesthetic, particularly a local anesthetic selected from the above-mentioned special local anesthetics, and the concentration of local anesthetic, depending on the specific active ingredient, is changed, in particular, from 3 wt.% up to 15 wt.%, especially from 6 wt.% up to 12 wt.%, depending on what concentratie active ingredient in the liquid composition.

Especially preferred local anesthetics selected from the group including benzocaine, procaine, tetracaine, lidocaine, etidocaine, prilocaine, mepivacaine, bupivacaine, S-ropivacaine, articaine and their derivatives.

Another variant implementation of the compositions of this invention provides a composition comprising at least one immunomodulator in concentration from 0.03 wt.% to 0.1 wt.%, and the above specific immunomodulators are particularly preferred.

Especially suitable modification of the composition of this invention contains as an active ingredient or mixture of active ingredients non-analgesic/anti-inflammatory agent, especially non-analgesic/anti-inflammatory selected from the above-mentioned special non-analgesics/anti-inflammatory. They include, in particular, salicylates, preferably acetylsalicylic acid and/or diflunisal, derivatives of acetic acids such as indomethacin, acemetacin, diclofenac and/or lonazolac, propionic acid derivatives, such as ibuprofen, flurbiprofen, Ketoprofen, dexketoprofen, dexibuprofen, tarenflurbil, nimesulide, naproxen and/or tiaprofenic acid, oxicam, such as piroxicam, tenoxicam, meloxicam and/or lornoxicam, derivatives of Anthranilic acid, such as Afanasyeva acid and/or flutamida acid, derivatives of aniline, such as paracetamol, and derivatives of 1-phenyl-2,3-dimethyl-3-pyrazolin-5-it, such as venison, propifenazona and/or Metamizole, their salts and their derivatives.

Depending on the particular application of the above-described embodiments of the composition of the present invention, the concentration of the active ingredient of analgesic/anti-inflammatory in the liquid composition will vary from 0.5 wt.% up to 8 wt.%, especially from 1 wt.% up to 5 wt.%.

Of course, it is also possible for the composition of this invention include as the active ingredient a mixture of active ingredients, because this mixture of ingredients mutually compatible. Such embodiments of the compositions of this invention will be applied to treatment is usually softer skin diseases, such as milder forms of eczema, acne, herpes, insect bites, fungal, and/or surface treatment of wounds foam formed from the composition of the present invention, and in this case, the active ingredient or mixture of active ingredients selected from the group consisting of terbinafine, clobetasone butyrate, erythromycin, benzocaine, dexamethasone, calcipotriol, tretinoin, Minoxidil, bifonazole, dexpanthenol, salicylic acid, prednicarbate, mometasone furoate.

Need to clarify that all data concentration specified in this description, each time attitudeto liquid composition before foaming, if it is not specified otherwise.

Particularly suitable variant of implementation of the compositions of the present invention includes as a phospholipid foaming means phosphatidylcholine isolated from soybeans, and, in particular, the concentration of phosphatidylcholine in the phospholipid foaming tool is more than 50 wt.%, preferably from 50 wt.% to 95 wt.%, relatively dry matter phospholipid foaming tool.

Especially when it phospholipid foaming agent contains, for the most part, 15 wt.% lyso-phosphatidylcholine, for the most part, 10 wt.% fosfatados acid and, for the most part, 10 wt.% phosphatidylethanolamine, it is possible to form the foam with this particular foaming agent, which can be different ways to adapt to the specific requirements of the application site by changing its concentration.

In addition, in some embodiments, the implementation for the above special foaming means can be important to phosphatidylcholine contained in the phospholipid foaming tool, had an acid number, for the most part, 10, peroxide number, for the most part 10, and the concentration of oil, for the most part, 6 wt.%, depending on the dry matter of this phospholipid foaming means, fluid composition, forming the basis of the foam is particularly glutelin the Yu persistence, not requiring higher concentrations of antioxidants or stabilizers, especially for the above-mentioned phospholipid foaming tool.

Mostly recorded that the concentration of phospholipid foaming tools contained in the liquid composition should be selected so as to form a foam, mentioned at the beginning for the method of this invention and the composition of the present invention and defined by the volume of foam and foam stability. Preferably, the liquid composition, which is completely mechanical foam has a phospholipid foaming agent in a concentration of from 2 wt.% up to 25 wt.%, especially at a concentration of 4 wt.% up to 15 wt.%.

General notes described above for the method of the present invention, are also supported for the composition of the present invention, where the composition of this invention contains, besides water, preferably an alcohol, and particularly propylene glycol, the concentration of which, depending on the desired and videopreteen foam varies from 2 wt.% up to 25 wt.%, particularly, from 5 wt.% up to 15 wt.%.

With regard to the pH values indicated that especially the liquid composition of this invention has a pH value that is tolerated by the skin and, depending on the specific location of application, lies between the 4.8 and 8.8.

To guarantee the above pH values, especially useful to add to the oppozitsii of the present invention, at least one buffer, especially dehydrate monopotassium phosphate and/or dodecahedral secondary acid phosphate.

The composition of the present invention, as described in detail above, can mainly be foamed by any suitable applicator for foam, for example, applicators manufactured by Rexam/Airspray (www.rexamairspray.com), and manufactured and sold under the name M3 minifoamer ("M3 Minischäumer"), or those that made Calmar/MeadWestvaco (Keltec). On this special applicator for foam, is described in EP 0565713 and EP 0613728, where will be found an additional process details of these applicators foam.

Thus, in particular, the invention provides an applicator for foam, which includes the composition of the present invention, as described in detail above.

Moreover, this invention relates to methods for treating the following diseases.

In the first embodiment, provides a method that includes the treatment of atopic eczema or neurodermatitis where the method of treatment of the present invention includes applying a foam containing immunomodulator, which is obtained in particular from the previously described composition of the present invention, on the skin of warm-blooded mammal, in need thereof. In particular, tacrolimus choose as immunomodulator. Depending on the choice of a specific immunomodulator, its concentration will vary preferably from 0.03 wt.% to 0.1 wt.%.

In the second embodiment, is provided a method of treating inflammatory or itchy skin diseases, psoriasis, dermatitis, neurodermatitis or psoriasis in a patient in need thereof, containing the application of a foam containing a glucocorticoid, which is obtained in particular from the described compositions to the skin of warm-blooded mammal. In particular, the glucocorticoid this method of treatment is selected from the group comprising betamethasone, dexamethasone, preincarnate, mometasone furoate and clobetasone batiratu depending on the glucocorticoid and its concentration varies from 0.01 wt.% up to 0.4 wt.%.

In the third embodiment, provides a method of treating pain, inflammation, arthritis or acute injury in a patient in need thereof, and includes the application of a foam containing an analgesic, which received, in particular from the previously described composition of the present invention, on the skin of warm-blooded mammal. Preferably, the analgesic in the treatment method selected from the group consisting of diclofenac, Ketoprofen and ibuprofen. Depending on the analgesic concentration varies from 0.5 wt.% up to 10 wt.%.

In the fourth embodiment, provides a method for the treatment of mycosis, containing the application of the foam, including about voglibose means, which is obtained in particular from the previously described composition of the present invention, skin or nails, respectively, hooves warm-blooded mammal, in need thereof. Preferably in this method of treatment antifungal agent selected from the group consisting of bifonazol and terbinafine. Depending on antifungal agent, its concentration varies from 0.1 wt.% up to 20 wt.%, preferably from 2 wt.% up to 10 wt.%.

In the fifth embodiment provides a method of treating infections gram-positive bacteria, anaerobic bacteria and mycoplasmas, especially for the treatment of acne, the patient, in need thereof, and includes the application of a foam containing an antibiotic, which received, in particular from the previously described composition of the present invention, on the skin of warm-blooded mammal. Preferably in this method of treatment is selected antibiotic is erythromycin, especially in a concentration of from 2 wt.% up to 4 wt.%.

In the sixth embodiment provides a method for the treatment of itching of the skin that contains the application of the foam, including a local anesthetic, which received, in particular from the previously described composition of the present invention, on the skin of warm-blooded mammal. Preferably in this method of treatment chosen by the local anesthetic is benzocaine and/or lidocaine, especially to the ncentratio from 1 wt.% up to 20 wt.%, preferably from 2 wt.% up to 10 wt.%.

In the seventh embodiment provides a method of treating psoriasis, containing the application of the foam, comprising calcipotriol, which is obtained in particular from the previously described composition of the present invention, on the skin of warm-blooded mammal, in need thereof. Preferably calcipotriol in this way to provide treatment at a concentration of 0.005 wt.% up to 0.05 wt.%.

In the eighth embodiment provides a method of treating acne, especially comedonal acne and papulopustular acne that contains the application of the foam, including tretinoin, which is obtained in particular from the previously described composition of the present invention, on the skin of warm-blooded mammal, in need thereof. Preferably in this method of treatment tretinoin provide in a concentration of from 0.05 wt.% to 0.1 wt.%.

In the ninth embodiment provides a method of treating hair loss, containing the application of the foam, including Minoxidil, which is obtained in particular from the previously described composition of the present invention, on the skin of warm-blooded mammal, in need thereof. Preferably in this method of treatment Minoxidil provide at a concentration of 3 wt.% up to 6 wt.%.

In the tenth embodiment provides a method antiseptic treatment of surface wounds, sod is riasi the application of the foam, which includes antifungal agent on the wound warm-blooded mammal, in need thereof, thus the foam is preferably obtained from the previously described composition of the present invention. In particular, in this method of treatment provides dexpanthenol in concentration from 0.03 wt.% up to 1 wt.%.

In the eleventh embodiment provides a method of treating herpes and side effects that accompany herpes, in a patient in need thereof, and includes the application of a foam containing acyclovir, which received, in particular from the previously described composition of the present invention, on the skin of warm-blooded mammal. Preferably in this method of treatment acyclovir provide at a concentration of 3 wt.% up to 7 wt.%.

In the twelfth embodiment provides a method of treating psoriasis of the skin of the skull from mild to moderate severity in a patient in need thereof, containing the application of the foam, including salicylic acid, which is obtained in particular from the previously described composition of the present invention, on the skin of the skull warm-blooded mammal. Preferably in this method of treatment salicylic acid to provide a concentration of 8 wt.% up to 12 wt.%.

In the above description of various embodiments of the method of treatment of this invention the expression of the application of the use of Aut in the singular. However, this shall also apply to repeated application at time intervals during this period, especially within 24 hours.

Similarly, the expression leather used throughout the text covers not only specific painful area of the skin, but also all surfaces of the human or animal body, open to the application of the foam obtained from the composition of the present invention, and thus in particular, in addition to the skin or skull leather, nails, hair, teeth, hooves or the mucous membrane of the mouth, nose, vagina or prepuce, the ear, and especially the inner ear, the area of the anus and colon, eye area, especially the area under the eyelid, such as the conjunctiva, cornea, and the lacrimal SAC, whereas the expression of the mammal includes animals and humans.

For clarity and to avoid repetition, indicated that notes, details and advantages described at the beginning in connection with the method of this invention also apply accordingly for the composition of the present invention and the above procedure of treatment of the present invention, as well as notes, details and advantages described in connection with the composition of the present invention, for the method of the present invention and procedures for the treatment of this invention.

Additionally, this invention relates to topically apply the ow of the liquid composition, containing at least one phospholipid foaming agent, at least one pharmaceutical active ingredient and at least one solvent. The composition of the invention foams exclusively mechanical foaming without the use of a propellant to such an extent that the mechanical foaming 250 ml of the liquid composition forms a foam having a volume of foam, at least 400 ml and the stability of the foam, which foam is still after the exposure time of approximately five minutes and preferably the exposure time up to five minutes, measured at 25°C, at least 50% of the volume of foam that was originally present immediately after the formation of the foam. And above the volume of the foam, and the aforementioned stability of the foam is measured in a standardized way to measure the SITA foam, described next. In this regard, it should be noted that the liquid composition is determined by the volume of foam and the foam stability, foam exclusively mechanically before applying without using a propellant, repeated as described above, so that the foam formed in this way was used for local application. This option is the implementation of the composition of this invention has all of the same or similar advantages as described previously. This is also the same for the above options is done by the means.

Preferably, the above composition of the invention has a volume foam, which varies from 450 ml to 1400 ml, especially from 600 ml to 1200 ml

Especially when the composition of the invention has such a stable foam, which is five minutes after the formation of the foam causes the volume of the foam, which corresponds to 55%-85% of the volume of the foam immediately after the formation of the foam, this variant implementation of the composition of the invention has a high pharmaceutical efficiency. This advantage is also present when the amount of foam is present within ten minutes after the formation of the foam, at least 50%, preferably from 85% to 100% of the volume of foam, which was originally present immediately after the formation of foam.

Especially the foam formed from a liquid composition according to the invention has a density of 0.05 g/ml to 0.8 g/ml, preferably from 0.15 g/ml to 0.4 g/ml

Relative to the solvent contained in the composition of the invention, it is necessary to specify that this solvent is preferably inorganic and/or organic solvent, thereby inorganic solvent is preferably water, and the organic solvent is an alcohol or mixture of alcohols, and more preferably polysperchon and/or solvents, as described earlier in section 5.

In addition, this izobreteny is preferably concerns a method for obtaining and/or development of a foaming liquid composition for local application, thus the method of this invention includes the following steps:

A. providing a liquid composition containing at least one pharmaceutically active ingredient, at least one solvent and at least one foaming agent, preferably, at least one phospholipid foaming agent;

b. mechanical foaming liquid composition;

C. study the surface of the foam to determine the stability and volume of foam;

d. changes in the concentration of at least one pharmaceutically active ingredient, at least one solvent, at least one foaming funds;

E. repeat steps b and C until 250 ml of liquid composition after mechanical foam will not have the volume of foam at least 400 ml and stability of the foam, which is at least approximately 50% of the original volume of the foam is still present after approximately 5 minutes at 25°C.

Also, this method of the present invention has the same or similar advantages and options for implementation.

The invention will be further described with the help of the following examples.

EXAMPLES

Description of the method of measurement SITA

To determine the amount of foam and the stability of the foam used tester foam "SITA R-2000" (manufactured SITA Messtechik GmbH, Dresden), as described in detail in the European patent document EP 1092970. This measuring device is provided to the rotor, as shown in Figure 2 and 3 of patent document DE Germany 19740095 and is also described there. This rotor consists of verhneprivodnaya stirrer and a round disk, oriented perpendicular to it, with a diameter of 70 mm above and below the circular disk provided four symmetric mixing blades are oriented at right angles to each other. Each mixing blade has a rectangular main surface 23 mm × 12 mm cross section of each mixing blade has the shape of a triangle with a height of 5 mm, so that each mixing surface respectively formed to overlap with a right angle of 90 degrees. Each of the stirring blades contains memperpanjang Conidur plate (manufactured HeinLehmann, Krefeld) and has a plate thickness of 0.5 mm, perforation 0.5 and spacing of 3.2.

When all the measurement sample volume was 250 ml, automatically selected by the measuring device from the surge tank filled with at least 300 ml of sample. The sample is carefully placed into the expansion tank, if possible, avoiding any foaming. After a timeout of ten minutes so that any air bubbles formed during the filling, could move to a surface the STI and thus, without distorting the volume, 250 ml sample was allowed space to measure and measured.

With a rotor speed of 2000 rpm (revolutions per minute) sample, measured in space to measure, were subjected to five rotor cycles of 20 seconds each for the formation of foam. Between rotor cycles was a pause of about 15 seconds.

Through sensors, described in German patent document DE 19949922, which automatically and continuously scanned the surface of the foam, the volume of foam was measured immediately after completion of the five rotary cycles. Foam stability is automatically determined by the instrument during the period a total of 35 minutes, for which the volume of foam was measured every 50 seconds by means of a needle detectors. Volume value, thus obtained, recorded directly designed software and hardware tools.

Control system tester foam SITA is such that after the space for measuring fill the 250 ml sample, needle detectors reach only the surface of the sample and, accordingly, place the zero point for the volume of foam on the surface of the measured sample and not the bottom of the space dimension. After passing the above-mentioned rotary cycles to produce a particular pattern in the space to change the texts sometimes remains liquid phase of the sample depending on the specific composition of the investigated sample, so the volume of this liquid phase is also determined by the above described measurement according to a particular measured value of the volume of foam and identified respectively as the amount of foam in the sense of this description, while the time changes in this volume of the foam is stable foam. In other words, this means that depending on the specific measured sample, the volume of foam is not only the volume of the actual foam, but also of the volume newspring liquid sample contained in the space for the dimension.

The following chart 1-18 represent all three measured values for a specific song, so this is very good you can see the reproducibility of the measurement method.

All the following examples, in which diclofenac is listed as the active ingredient, contain this active ingredient in the form of the sodium salt of diclofenac, called diclofenac-sodium.

EXAMPLES 1-4

After the usual procedure has prepared a composition comprising Ketoprofen, a composition containing lidocaine hydrochloride composition containing prednicarbate, the composition comprising diclofenac, and composition containing clotrimazole, containing the following ingredients:

IngredientComposition in ve is.%
1Ketoprofen10,00
2Propylene glycol10,00
32-propanol8,00
4Phospholipid foaming agent And10,00
5Dehydrate monopotassium phosphate0,25
6Dodecahydrate secondary acid phosphate, Krist.0,57
7Sodium hydroxide1,55
8Mint oil0,15
9Water of the highest purity59,48
ONLY100,00

The behavior of this foam composition 1 shown in figure 1.

IngredientComposition, wt.%
1Lidocaine hydrochloride10,00
2Propylene glycol10,00
32-propanol11,00
4Phospholipid foaming agent And10,00
5Dehydrate monopotassium phosphate0,12
6Dodecahydrate secondary acidic sodium phosphate, Krist.0,66
7Sodium hydroxide 20% W/W4,00
8Mint oil0,15
9Water of the highest purity54,07
ONLY100,00

The behavior of this foam composition 2 shown in figure 2.

IngredientComposition, wt.%
1Prednicarbate0,10
2Propylene glycol15,00
32-propanol9,35
4Phospholipid foaming agent In5,00
5Dehydrate monopotassium phosphate0,50
6Dodecahydrate secondary acid phosphate, Krist.1,14
7Sodium hydroxide 10% weight/weight1,00
8Tegosoft GC8,60
9Water of the highest purity59,31
ONLY100,00

The behavior of the foam of this comp is the position 3 shown in Figure 3.

IngredientComposition, wt.%
1Clotrimazole0,5
2Propylene glycol20,00
32-propanol8,00
4Phospholipid foaming agent And8,00
5Dehydrate monopotassium phosphate0,12
6Dodecahydrate secondary acid phosphate, Krist.0,66
7Sodium hydroxide 20% W/W1,00
8Mint oil0,20
9Polysorbate 8013,00
10Water of the highest purity 48,52
ONLY100,00

The behavior of this foam composition 4 is shown in Figure 4.

Twenty subjects (11 women, 9 men)suffering from fungal infections between the toes and also partially on the toe had the area affected by the fungus, on the left foot, treated twice a day foam obtained by the above described method of measuring SITA. Processing completed so that the painful area is covered with a foam layer approximately 0.5 to 1 cm thickness, and then the foam was rubbing manually. The total processing time lasted up to 14 days.

The painful area of the right foot was treated with composition 4 with identical ingredients, while this song 4 wspanile through "M3 minifoamer" from Rexam/Airspray before application.

Regardless of what the foam was applied to the painful area, 16 subjects reported a clear decrease itching even after the first application specific foam. Two other subject reported that the reduction of itching after two of applying, and the remaining two subjects reported a decrease in itching after four applications.

Ten subjects fungal infection was eliminated after the whole processing time in eight days, six of the subjects of healing time was eleven days, and four sub is known healing time was 14 days. Noted that the last four subjects were more severely affected by the fungal infection. None of the subjects could not tell the difference between the foam formed by the method of measurement SITA, and the foam obtained with "M3 minifoamer".

EXAMPLES 5-7

To study the effect of concentration of active ingredient in the foam prepared with the following composition 5-7 and investigated the relative concentrations of the active ingredient of diclofenac.

IngredientComposition, wt.%
1Diclofenac1,000
2Propylene glycol15.000
32-propanol10,250
4Ascorbyl palmitate0,020
5Phospholipid foaming agent And13,330
6Dehydrate monopotassium phosphate sodium, high purity0,120

7Dodecahydrate secondary acid phosphate, Krist.0,660
8EDTA0,040
9Water of the highest purity59,380
10Peppermint oil, purified0,200
ONLY100,00

The behavior of the foam the composition 5 is shown in Figure 5.

IngredientComposition, wt.%
1Diclofenac2,000
2Propylene glycol15.000
32-propanol10,250
4Ascorbyl palmitate0,020
5 Phospholipid foaming agent And13,330
6Dehydrate monopotassium phosphate0,120
7Dodecahydrate secondary acid phosphate, Krist.0,660
8EDTA0,040
9Water of the highest purity58,380
10Peppermint oil, purified0,200
ONLY100,00

The behavior of the foam the composition 6 is shown in Fig.6.

IngredientComposition, wt.%
1Diclofenac8,000
2Propylene glycol15.000
32-Propanol 10,250
4Ascorbyl palmitate0,020
5Phospholipid foaming agent And13,330
6Monopotassium phosphate sodium dihydrate0,120
7Secondary acid phosphate sodium Dodecahydrate, Krist.0,660
8EDTA, Titriplex III0,040
9Water of the highest purity52,380
10Peppermint oil, purified0,200
ONLY100,00

The behavior of the foam the composition 7 is shown in Fig.7.

On the basis of comparison compositions 5-7 and the corresponding figures 5-7 we can say that the volume of the foam increases with almost constant stability of the foam, as it increases the concentration of the active ingredient.

EXAMPLES 8-10

To study the effect of concentration of phospholipid is about blowing money on the foam prepared with the following composition 8-10 and researched on the concentration of phospholipid foaming tool.

IngredientComposition, wt.%
1Diclofenac4,000
21,2-propandiol15,000
32-propanol10,250
4L ( + ) - ascorbyl palmitate0,020
5Phospholipid foaming agent And2,000
6Dehydrate monopotassium phosphate sodium, high purity0,120
7Dodecahydrate secondary acid phosphate, high purity0,660
8EDTA0,040
9Water of the highest purity67,710
10the pleasant oil, cleared0,200
ONLY100,00

The behavior of foam in the song 8 shown in Fig.

IngredientComposition, wt.%
1Diclofenac4,000
21,2-propandiol15,000
32-propanol10,250
4L ( + ) - ascorbyl palmitate0,020
5Phospholipid foaming agent And5,000
6Dehydrate monopotassium phosphate sodium, high purity0,120

7Dodecahydrate secondary acid phosphate, high purity0,660
8EDTA0,040
9Water of the highest purity64,710
10Peppermint oil, purified0,200
ONLY100,00

The behavior of this foam composition 9 is shown in Fig.9.

0,120
IngredientThe composition of the Aria.%
1Diclofenac4,000
21,2-propandiol15,000
32-propanol10,250
4L ( + ) - ascorbyl palmitate0,020
5Phospholipid foaming agent And20,000
6Dehydrate monopotassium phosphate sodium, high purity
7Dodecahydrate secondary acid phosphate, high purity0,660
8EDTA, Titriplex III0,040
9Water of the highest purity49,710
10Peppermint oil, purified0,200
ONLY100,00

The behavior of the foam the composition 10 is shown in Figure 10.

On the basis of comparison compositions 8-10 and the corresponding figures 8-10, you can say that the volume of the foam is reduced with almost constant stability of the foam, since the concentration of phospholipid foaming funds increases.

EXAMPLES 11-13

To study the effect of concentration of isopropanol in the foam of the following composition 11-13 were prepared and investigated regarding the concentration of isopropanol.

IngredientThe composition of the Aria.%
1Diclof the NAC 4,000
2Propylene glycol15,000
32-propanol5,000
4Ascorbyl palmitate0,020
5Phospholipid foaming agent And13,330
6Dehydrate monopotassium phosphate0,120
7Dodecahydrate secondary acid phosphate, Krist.0,660
8EDTA0,040
9Water of the highest purity61,630
10Peppermint oil, purified0,200
ONLY100,00

The behavior of this foam composition 11 is shown at 11.

IngredientComposition, wt.%
1Diclofenac4,000
2Propylene glycol15.000
32-propanol10,000
4Ascorbyl palmitate0,020
5Phospholipid foaming agent And13,330
6Dehydrate monopotassium phosphate0,120
7Dodecahydrate secondary acid phosphate, Krist.0,660
8EDTA0,040
9Water of the highest purity56,630
10Peppermint oil, purified0,200
ONLY100,00

The behavior of foam in the song 12 shown in Fig.

IngredientComposition, wt.%
1Diclofenac4,000
2Propylene glycol15.000
32-propanol20,000
4Ascorbyl palmitate0,020
5Phospholipid foaming agent And13,330
6Dehydrate monopotassium phosphate0,120
7Dodecahydrate secondary acid phosphate, Krist.0,660

8EDTA0,040
9In the and the highest degree of cleaning 46,630
10Peppermint oil, purified0,200
ONLY100,00

The behavior of foam in the song 13 shown in Fig.

On the basis of comparison compositions 11-13 and the corresponding figures 11-13 we can say that the volume of the foam increases as a function of the concentration of isopropanol with increasing concentrations of isopropanol from 5 wt.% up to 10 wt.% and then decreases again in the range of 10 wt.% up to 20 wt.%, so does not form a stable foam at a concentration of 20 wt.% isopropanol. The small volume of the foam, originally shown on Fig must be ignored.

EXAMPLES 14-16

To study the effect of concentration of propylene glycol on the foam prepared with the following composition 14-16, differs depending on the concentration of propylene glycol.

IngredientComposition, wt.%
1Diclofenac4,000
21,2-propandiol5,000
32-prepupal10,250
4L ( + ) - ascorbyl palmitate0,020
5Phospholipid foaming agent And13,330
6Dehydrate monopotassium phosphate sodium, high purity0,120
7Dodecahydrate secondary acid phosphate, high purity0,660
8EDTA0,040
9Water of the highest purity66,380
10Peppermint oil, purified0,200
ONLY100,00

The behavior of the foam the composition 14 is shown in Fig.

IngredientComposition, wt.%
1Diclofenac4,000
21,2-propandiol10,000
32-propanol10,250
4L ( + ) - ascorbyl palmitate0,020
5Phospholipid foaming agent And13,330
6Dehydrate monopotassium phosphate sodium, high purity0,120
7Dodecahydrate secondary acid phosphate, high purity0,660
8EDTA0,040
9Water of the highest purity61,380
10Peppermint oil, purified0,200
ONLY100,00

The behavior of the foam Dunn is the first composition 15 is shown in Fig.

IngredientComposition, wt.%
1Diclofenac4,000
21,2-propandiol20,000
32-propanol10,250
4L ( + ) - ascorbyl palmitate0,020
5Phospholipid foaming agent And13,330
6Dehydrate monopotassium phosphate sodium, high purity0,120
7Dodecahydrate secondary acid phosphate, high purity0,660
8EDTA0,040
9Water of the highest purity51,380
10Mint oil, cleared0,200
ONLY100,00

The behavior of the foam the composition 16 is shown in Fig.

On the basis of comparison compositions 14-16 and the corresponding figures 14-16 we can say that the concentration of propylene glycol has no or only a very small influence on the amount of foam and foam stability.

EXAMPLE 17

In a comparative study, 14 subjects (8 women, 6 men) with a pronounced acne on the facial area, subjects were treated twice a day (morning and evening) foam made from the composition, the ingredients of which are expressed quantitatively in the following table for the track 17.

IngredientComposition, wt.%
1Erythromycin1,50
2Propylene glycol15,00
32-propanol9,35
4Phospholipid foaming agent In8,00
5Dehydrate monopotassium phosphate0,50
6dodecahydrate secondary acid phosphate, Krist.1,14
7Sodium hydroxide 10% weight/weight1,00
8Tegosoft GC7,70
9Water of the highest purity55,81
ONLY100,00

The behavior of foam in the song 17 shown in Fig.

Processing completed by applying a certain amount of 0.4 mg foam half face. The foam was applied directly on the treated area and rubbed in a circular motion 2 fingers. The total time of therapy reached 60 days.

Every time the left half of the face of each subject was treated foam made using the above-described method of measuring SITA, and the right half of the face of each subject using a foam obtained by using "M3 minifoamer" from Rexam/Airspray, both foam prepared from the composition 17.

The first success which can already be determined for both pins 30 days after application: damage on the left side of the face has decreased by about 19% and the right side approximately 21%.

When the final assessment 60 day trials found a reduction in damage by approximately 36% on the left side of the face and a decrease of approximately 34% from the right side of the face. It was impossible to determine a significant difference between the two halves of the face. None of the subjects did not perceive the treatment as unpleasant or not reported painful irritation of the treated areas. No one has been able to establish differences in tolerability of treatment between the two halves of the face.

EXAMPLE 18

In a double-blind, randomized and placebo controlled comparative study of 12 subjects (5 women, 7 men) investigated the effectiveness of

a) the above composition 9, containing 4% of diclofenac-sodium

b) the above composition 1, containing 10% Ketoprofen, and

c) the effectiveness of the composition without Ketoprofen, which was identical to composition 1, depending on the ingredients 2-9, this composition without Ketoprofen did not contain Ketoprofen and instead had a 10 wt.% more water than composition 1,

in the treatment of artificially induced UV erythema. All used foam was obtained using the above described measuring method SITA, and "M3 minifoamer" from Rexam/Airspray, on the basis of the same initial composition.

Artificial UV erythema created on 16 test areas (each 2×2 cm) on the back, 4 t is struebig areas left and right of the spine, and 4 test areas on the lower division and upper back. 8 upper Guinea regions were subjected to a UV dose of 1.5 × MED and lower test area of 2.5 × MED.

After UV-exposure ring ECG with an inner diameter of 16 mm was glued with the centers of UV-irradiated test areas. Untreated areas were also marked by rings ECG. The distance between the tested areas was approximately 3 see

Further, approximately 10-15 minutes before the end of the UV irradiation, the dose of 25 µg foam according to a random list used in rings ECG and evenly distributed using a round knife.

The behavior of the foam composition 18 (C) (composition without Ketoprofen) is shown in Fig.

Assessment of differences was done using optical research conducted by a dermatologist. It was conducted on the basis of an internationally recognized method of visual assessment from 0 = no visible erythema to 4 = intense erythema for untreated surface and assessment -1 = intense erythema to 3 = completely stopped erythema for irradiated and treated areas. Validation was done through 2, 3, 4, 5, 6, and 8 hours on the same day as the application.

Between the foams obtained according to the method of measurement SITA and the same, using "M3 minifoamer", found a small value for the active ingredient Ketoprofen, only at one point in time PR is measurement: 6 hours. This difference was insignificant. Here, the value of erythema 2 found for the foam, which is obtained accordingly to the method of measurement SITA, and a value of 1 for the foam, which is obtained by using "M3 minifoamer". No other differences could be detected between the foams obtained in various ways and containing the active ingredient.

Compared to a composition not containing Ketoprofen, (s) and raw test areas, the foam containing the active ingredient, showed clear differences in MED 1,5 and 2,5 MED at final measurement after 8 hours.

Especially the 2.5 MED, a value of 1 was detected for the foam containing diclofenac (small suppression of erythema, easily identifiable), the value of 2 for foam containing Ketoprofen (clear suppression of erythema, but still visible) and a value of -1 for foam without Ketoprofen (clearer erythema). The foam obtained from the composition containing Ketoprofen, shows a clear therapeutic advantage over foam containing diclofenac, foam without Ketoprofen and raw test regions.

All of the foam containing the active ingredient, showed good tolerability. Three (3) side effect was found only for foam without Ketoprofen.

Phospholipid foaming agent As used above in examples 1 and 2 and 4-16, had the following composition with following the mi values, relatively dry matter.

Phosphate milholin80 wt.% ± 10 wt.%
Lysophosphatidylcholine3 wt.% ± 3 wt.%
Phosphatidic acid≤8 wt.%
The phosphatidylethanolamine≤4 wt.%
Other oil componentsmax 6 wt.%
Acid number2
Peroxide number6

Phospholipid foaming agent In used above in examples 3 and 17, has the following composition with the following values, relative to the dry matter.

Phosphatidylcholine85 wt.% ± 10 wt.%
Lysophosphatidylcholine3 wt.% ± 3 wt.%
Tocopherolmax 0.3 wt.%
Acid number1
Peroxide number5

The above-mentioned peroxide number indicates milliequivalent oxygen, which is contained in 1000 g of sample (dry matter). It is, after reaction of the sample with potassium iodide in a mixture of chloroform and acetic acid was determined by titration of iodine obtained in this way, sodium thiosulfate, and potentiometric definition.

Acid number indicates how many mg of potassium hydroxide necessary to neutralize free nonesterified fatty acids contained in 1 g of phospholipid foaming tool (dry matter). This value is determined by titration of the corresponding dissolved sample solution of potassium hydroxide using phenolphthalein as an indicator.

1. Method development in liquid pharmaceutical compositions applied in the form of foam on the skin, comprising the steps are:
a) to provide a liquid composition containing:
- at least one pharmaceutical active ingredient,
- solvent mixture containing water, isopropanol in an amount of 5 wt.% up to 20 wt.% and propylene glycol in an amount of from 2 wt.% up to 25 wt.%, and
- at least one phospholipid foaming agent in an amount of from 2 wt.% up to 25 wt.%,
b) mechanically foaming liquid composition without the use of a propellant;
c) determine the volume of foam and foam stability;
e) repeat steps c) and d)until 250 ml of the liquid composition will not form a foam with a volume of at least 400 ml and stability of foam that is at least 50% of the original volume of the foam is still present after the exposure time to 10 minutes, and the volume of foam and foam stability together to define a standardized way of measuring SITA.

2. The method according to claim 1, characterized in that steps C) and d) are repeated until the formed foam will not have such stability of foam that at least 50% of the original volume of the foam is still present after the exposure time to 5 minutes.

3. The method according to claim 1 or claim 2, characterized in that steps c) and d) are repeated until the formed foam will not have the amount of foam from 450 to 1400 ml, preferably from 600 to 1200 ml.

4. The method according to claim 1 or claim 2, characterized in that steps c) and d) are repeated until the formed foam will not have such stability of foam that from 55% to 100%, preferably from 85% to 99% of the original volume of the foam is still present after the delay time.

5. The method according to claim 1, characterized in that between the foam formed and established way of measuring SITA, and pharmaceutical properties, provide the correlation.

6. The method according to claim 1, characterized in that the mechanical foaming liquid composition wybir the t applicator for foam, the foam is formed from a liquid composition selected applicator for foam and between the pharmaceutical properties of the foam formed by means of an applicator for foam and foam defined and formed by using the method of measurement SITA, provide correlation.

7. The method according to claim 1, characterized in that such a foam is formed from a liquid composition that has a density of foam from 0.05 g/ml to 0.8 g/ml, preferably from 0.15 g/ml to 0.4 g/ml, using the method of measuring the SITA foam.

8. The method according to claim 1, characterized in that the mixture of solvents for the liquid composition further comprises glycerin.

9. The method according to claim 1, characterized in that for forming the liquid composition used complexing agents, buffers, thickening agent, antioxidant and/or stabilizer.

10. The composition is suitable for topical application,
(a) where the composition comprises at least one systemically and/or topically active pharmaceutically active ingredient, a mixture of solvents containing water, isopropanol in an amount of 5 wt.% up to 20 wt.% and propylene glycol in an amount of from 2 wt.% up to 25 wt.%, and at least one phospholipid foaming agent in an amount of from 2 wt.% up to 25 wt.%;
b) is of such a consistency of the liquid, when applied forms a foam, and at least one phospholipid foaming agent, see the camping solvent and at least one pharmaceutically active ingredient blended with each other by their chemical nature and/or their concentration so the mechanical composition foams without the use of additional propellant;
c) where the resulting foam has a volume of foam at least 400 ml, preferably from 450 to 1400 ml and especially the amount of foam from 600 to 1200 ml, and stability of the foam, whereby the foam still has after the exposure time of ten minutes and especially after the exposure time up to five minutes at least 50% of the volume of foam and especially from 55% to 100% of the volume of foam and preferably from 85% to 99% of the volume of foam that were originally present immediately after foaming;
d) and the volume of foam and foam stability are defined in a standardized way of measuring the SITA foam.

11. The composition of claim 10, where the foam has a density of 0.05 g/ml to 0.8 g/ml, preferably from 0.15 g/ml to 0.4 g/ml

12. The composition according to any one of p or 11, characterized in that the composition comprises a phospholipid foaming means a phospholipid selected from components of the plant and/or phospholipid mixture.

13. The composition according to claim 10, characterized in that at least one active ingredient is an active ingredient for use in humans or animals and is selected from the group consisting of local anesthetics, anti-allergic medicines, skin, active ingredients against flu infections and simply is, active ingredients for the treatment of neuropathies, active ingredients for the treatment of circulatory disorders, drugs for chemotherapy, quinine, antifungals, antibiotics, thalidomide, serotonin, eicosanoids, analgesics, anti-convulsants, non-steroidal Antirheumatic agents, leukotrienes, leukotriene inhibitors, androgens, antiandrogens, corticoid, antagonists of opioid receptors, inhibitory substances for blood clotting, platelet aggregation inhibitors, histamine antagonists, regulatory and enzymatic active peptides and proteins, nucleic acids (single - and double-helical DNA, single and double helix RNA, snRNA, DNA oligonucleotides, RNA oligonucleotides) and oligopeptides, antipruritic, anti-diabetic, prostaglandins and inhibitors of prostaglandin synthesis, antiviral active or virusstatus active substances, anti-microbial active substances, active ingredients against prion, immune suppressors, hormones, active ingredients for the treatment of warts or wounds, especially chronic wounds, vitamins, plant extracts or essences herbal extracts, psychotropic drugs, active ingredients that affect sleep, analeptics, General anesthetics, muscle relaxants, anticonvulsants, antiparkinsonian with whom estva, antiemetic, anti-parasitic, ganglion-active ingredients, simpaticeskii active ingredients, parasimpaticheskih active ingredients, proteobacterial existing drugs, calcium antagonists, cardiovascular drugs, Antiasthmatic, antitussive, expectorant, acting on the liver, diuretics, choleretic, bleach, trace elements, anti-infective, cytotoxic agents, antimetabolites, hormone antagonists, immunomodulators, and derivatives and salts of the above-mentioned active ingredients.

14. The composition according to item 13, wherein the at least one analgesic contained in the composition in a concentration of from 0.1 wt.% up to 20 wt.%, preferably in a concentration of between 2 wt.% up to 10 wt.%.

15. The composition according to item 13, wherein the at least one antifungal agent contained in the composition in a concentration of from 0.01 wt.% up to 10 wt.%, preferably in a concentration of from 0.2 wt.% up to 5 wt.%.

16. The composition according to item 13, wherein the composition comprises at least one corticoid active ingredient in a concentration of from 0.001 wt.% up to 3 wt.%, preferably from 0.1 wt.% to 0.8 wt.%.

17. The composition according to item 13, wherein the composition comprises at least one local anesthetic at a concentration of 3 wt.% up to 15 wt.%, especially from 6 wt.% up to 12 wt.%.

18. To notice indicated in paragraph 13 characterized in that the composition contains at least one immunomodulator in concentration from 0.03 wt.% to 0.1 wt.%.

19. The composition according to claim 10, characterized in that the composition comprises a phospholipid foaming means phosphatidylcholine isolated from soybeans, and that the concentration of phosphatidylcholine in the phospholipid foaming tool is more than 50 wt.%, especially from 50 wt.% to 95 wt.%, relatively dry matter.

20. The composition according to claim 19, characterized in that at most 15 wt.% lyso-phosphatidylcholine at most 10 wt.% fosfatidinozitol acid and at most 10 wt.% phosphatidylethanolamine is contained in the phospholipid foaming agent.

21. The composition according to PP or 20, characterized in that the phosphatidylcholine contained in the phospholipid foaming tool has an acid number of at most 10, peroxide number, at most, 10 and the concentration of oil at most 6 wt.%.

22. The composition according to claim 10, characterized in that the composition comprises a phospholipid foaming agent in a concentration of from 2 wt.% up to 25 wt.%, preferably at a concentration of 4 wt.% up to 15 wt.%.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula I: cis-COOR-XCH-(CH2)a-CH=CH-(CH2)b-CH3, wherein (a) and (b) can take any value from 0 to 14, (X) is specified in: OH, NH2, CH3, F, F3C, HS, O-CH3, PO4(CH2-CH3)2 and CH3COO, and (R) represents sodium (Na) applicable for preventing and/or treating obesity, hypertension and/or cancer. Also, the invention refers to using the compounds of formula I for preparing a pharmaceutical and/or nutrient composition, to the pharmaceutical and/or nutrient composition based on the compounds of formula I, to a cosmetic, non-therapeutic method for improving skin manifestations and to a method for preventing and/or treating the diseases in humans and animals with using the compounds of formula I.

EFFECT: preparing the new compounds.

18 cl, 22 dwg, 5 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is a group of inventions containing a combination of the avermectine compound specified in ivermectine, invermectine, avermectine, abamectine, doramectine, eprinomectine and selamectine, aversectine B, AB or C, emamectine B1a, emamectine B1b and their derivatives, or latidectine, and the alpha-2 adrenergic receptors agonist compound specified in apraclonidine, brimonidine, clonidine, dexmedetomidine, guanabenze acetate, lidamidine, lofexidine, methyldopa, rilmenidine, talipexole, tiamenidine, tizanidine, tolonidine or salts thereof, to be used as a therapeutic agent in treating and/or preventing rosacea, including eye rosacea, using the above combination for preparing the therapeutic agent applicable for treating and/or preventing rosacea, a product in the form of a kit and a pharmaceutical composition of the same formulation and application both, using the above product for preparing the therapeutic agent for treating and/or preventing rosacea.

EFFECT: what is shown is the synergetic effect of the combination in treating rosacea and eliminating the withdrawal effect usually observed at the end of treatment with alpha-2 adrenergic receptor agonists.

20 cl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a water-soluble complex of β-cyclodextrine-histochrome initiation with a molar ratio of the said components from 1:1 to 3:1. To obtain an initiation complex at the first stage performed are: mixing of dry β-cyclodextrine with bidistilled water (DDH2O), shaking the solution at a temperature of 55-65°C until total dissolution, after which cooling of the solution to 37-45°C is realised, at the second stage a 1% solution of histochrome in a volume, necessary for obtaining the necessary concentration is added to the obtained solution, after which the solution is subjected to shaking at 25-45°C for 1.5-2 hours.

EFFECT: prolonged antioxidant action.

2 cl, 4 dwg, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the pharmaceutical industry, namely to an extract of Nerium oleander in aloe. A method of obtaining the extract of Nerium oleander in aloe includes mixing vegetable material, which contains leaves and stems of the Nerium oleander plant, with vegetable mucus of aloe with obtaining an extraction mixture, conditioning the said extraction mixture with obtaining the extract of Nerium oleander in aloe. The composition of cardiac glycosides and aloe for treatment of a pathological state of skin, selected from sun-damaged skin, ageing skin, acne, age spots, liver spots, sunburn and herpes. A pharmaceutical composition for treatment of the pathological state of skin. A method of treating the pathological state of skin. A method of the cosmetic composition application.

EFFECT: described above extract and based on it preparations are efficient.

14 cl, 7 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, specifically dermatology, and can be used for treating patients with pemphigus vulgaris. That is ensured by prescribing prednisolone in a dose of 1 mg/kg/day for 7 days. On the 7th day, Metoject is administered subcutaneously in a dose of 7.5 mg once a day for 3-4 weeks. On the following day of the above administration, the dose of prednisolone is reduced by 1/3, after the following injections, the dose of prednisolone is reduced by 5-10 mg after each following injection.

EFFECT: invention enables providing higher clinical effectiveness in the patients with pemphigus vulgaris with a lower risk of complications.

2 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely to therapy, and can be used for treatment of scleroderma. For this purpose, a therapeutically efficient quantity of type I interferon (IFN) antagonist, where the said antagonist is represented by an antibody, is introduced to a patient in need. The group of inventions also relates to a method of reducing intensity of one or more symptoms, associated with scleroderma.

EFFECT: application of type I interferon antagonist, namely the antibody, makes it possible to suppress transmission of IFN signal with the participation of άIFN receptor, which substantially reduces the probability of development and severity of inflammatory disease of skin and contributes to skin recovery.

20 cl, 8 ex, 9 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a novel derivative of N-acylanthranilic acid, represented by the following general formula 1, or to its pharmaceutically acceptable salt, in which R1, R2, R3, X1, X2, X3, X4 and A are determined in the invention formula.

EFFECT: invention relates to an inhibitor of collagen production, a medication for treating diseases, associated with the excessive production of collagen, containing N-acylanthranilic acid derivative Formula 1.

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound of formula [I] or to its pharmaceutically acceptable salt, wherein A represents optionally substituted alkyl, wherein the substitute represents identical or different 1-3 groups specified in aryl optionally substituted by 1-3 groups specified in alkyl, halogen, alkoxy and alkanoyl; cycloalkyl optionally substituted by 1-3 groups specified in alkyl and halogen; hydroxy; alkoxy; halogen; an amino group and oxo; an optionally substituted carbocyclic group specified in a mono- and bicyclic group, wherein an aromatic ring and cycloalkyl are condensed; optionally substituted aryl, an optionally substituted completely saturated 5- or 6-merous monocyclic heterocyclic group each of which contains 1 heteroatom specified in nitrogen and oxygen, wherein the substitute of optionally substituted aryl, the optionally substituted carbocyclic group and the optionally substituted heterocyclic group for A represents identical or different 1-3 groups specified in alkyl, optionally substituted hydroxy, alkoxy, cycloalkyl or halogen; cycloalkyl optionally substituted by alkyl or alkoxy; alkoxy optionally substituted by halogen; halogen; hydroxy; oxo; heterocycle; alkyl sulphonyl; and mono- or dialkylcarbamoyl, optionally substituted amino, wherein the substitute represents identical or different 1 or 2 alkyl or aryl, or optionally substituted carbamoyl, wherein the substitute represents identical or different 1 or 2 alkyls optionally substituted by aryl, X represents optionally substituted methylene or -O-, wherein the substitute of optionally substituted methylene for X represents alkoxy or hydroxy, Q represents N or C-R4, L1 represents a single bond, methylene, -CH=CH-, -O-, -CO-, -NR11-, -NR11CO-, -CONR11- or -CH2NR11-, L2 represents a single bond, -CR6R7- or a bivalent 5- or 6-merous completely saturated monocyclic heterocyclic group each of which contains 1 heteroatom specified in nitrogen and oxygen, R1 and R2 are identical or different, and each represents hydrogen, alkyl or halogen, R3 and R4 are identical or different, and each represents hydrogen, alkyl, alkoxy, cyano or halogen, R1 and R3 are optionally bond thereby forming 5- or 6-merous cycloalkane, or a 5- or 6-merous aliphatic heterocycle containing oxygen atom, R5 represents a carboxyl group, an alkoxycarbonyl group or a bioisosteric group of the carboxyl group, R6 and R7 are identical or different, and each represents hydrogen or alkyl, or R6 and R7 are bond thereby forming cycloalkane, R8 represents hydroxy, alkanoylamino or alkyl sulphonylamino, R9 and R10 represent hydrogen or halogen, and R11 represents hydrogen or alkyl. Besides, the invention refers to specific compounds of formula [I], a drug based on the compound of formula [I], using the compound of formula [I], a method of treating based on using the compound of formula [I], and an intermediate compound of formula [II].

EFFECT: there are prepared new compounds possessing the agonist activity on thyroid hormone β receptor.

18 cl, 36 tbl, 344 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to phytotherapy and cosmetology, namely to a composition for internal use for hormone skin aging correction. The composition for internal use for hormone skin aging correction contains yam root extract, one or more antioxidants specified in vitamin C, vitamin E, coenzyme Q10, as well as hyaluronic acid taken in certain proportions.

EFFECT: above composition effectively corrects the hormone skin aging, builds up skin density and tightness by stimulating collagen-elastin fibre production and promoting antioxidant protection.

12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: pharmaceutical oil-in-water emulsion contains mometasone or mometasone furoate, propylene glycol and water. The propylene glycol concentration makes from 20 to approximately 45 wt %. A mass ratio of propylene glycol and water in the oil-in-water emulsion makes from 1:1 to approximately 1:3. A portion of mometasone or mometasone furoate is found insoluble in the emulsion.

EFFECT: composition is characterised by stability and therapeutic effect.

27 cl, 6 dwg, 5 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: stabiliser includes modified chitosan which is obtained by modifying chitosan particles located in an emulsion of an organic solvent - water, with pH 6.0-6.5, by first reacting a mixture consisting of a carboxylic acid in an organic solvent and a condensing agent, and then with an organic base, wherein the carboxylic acid used is either palmitic acid or stearic acid or dodecanoic acid, the condensing agent used is a mixture of hydroxysuccinimide and an aliphatic carbodiimide or formaldehyde and an aliphatic isocyanide, and the organic base used is triethylamine.

EFFECT: effective liposome composition stabiliser which can be obtained using a simple method.

8 cl, 3 tbl, 5 ex, 7 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a carrier applicable for the local drug delivery. A drug is enclosed in a carrier, and the carrier comprises a coating able to release an enclosed drug as a result of a local stimulus. The coating additionally surrounds the contrast agent MR 19F which changes its detectability after being released from the carrier. The invention refers to a method for the drug delivery to an MRT-controlled individual, wherein the method involves administering the above carrier into the individual enabling the carrier releasing the drug, and forming MR 19F images with the use of a contrast produced by the contrast agent MR 19F.

EFFECT: invention enables monitoring the beginning of the drug release from the carrier.

18 cl, 11 dwg, 2 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and concerns irinotecan liposomes or its hydrochloride containing irinotecan or its hydrochloride, neutral phospholipid and cholesterol, wherein the weight ratio of cholesterol to neutral phospholipid makes 1:3-5, and a method for preparing them.

EFFECT: liposomes have higher stability.

15 cl, 3 dwg, 10 tbl, 10 ex

FIELD: medicine.

SUBSTANCE: inhalation aerosol formulation for treating respiratory diseases contains salmeterol or salmeterol xinafoate, fluticasone or fluticasone propionate, a propellent modifier representing perfluorodecalin, and a propellent specified in 1,1,1,2 tetrafluoroethane (HFA-134a) and/or 1,1,1,2,3,3,3-heptafluoropropane (HPA-227ea).

EFFECT: higher respirable fraction and effective pulmonary delivery of the active ingredient; the aerosol has higher stability.

1 dwg, 6 ex

FIELD: medicine.

SUBSTANCE: inhalation formulation in the form of aerosol for treating bronchial asthma and chronic obstructive pulmonary disease containing ipratropium bromide monohydrate as an active ingredient, ethanol absolute as a solvent, an aerosol particle size regulator as an adjuvant consisting of triethyl citrate and an acid specified in a group: citric acid, hydrochloric acid, orthophosphoric acid, 1,1,1,4-tetrafluoroethane (HFA-134a) and/or 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea) as a propellant in certain proportions.

EFFECT: increasing the respirable fraction and obtaining an optimised particle size distribution profile.

7 ex

FIELD: medicine.

SUBSTANCE: invention refers to methods of treating a patient suffering from severe and uncontrolled asthma which involve pulmonary administration of a glucocorticoid in the form of a vapour-phase nebulised aerosol in a combination with oral administration of a glucocorticoid. According to one of the declared methods, the nebulised aerosol is administered by inhalation at no more than 20 l/min rate in the total inhalation volume of at least 0.4 l of the vapour phase; t administration of the nebulised aerosol is preceded by administering no more than 150 ml of aerosol-free air. The glucocorticoid is administered in a daily dose of no more than 40 mg of prednisolone and an equivalent dose of another glucocorticoid. The other method of treating the patient involves pulmonary administration of the glucocorticoid in an amount of 400 to 4,000 mcg with using a nebuliser which is used to administer the glucocorticoid aerosol into the lower portion of the lungs at excessive pressure of 40 mbar or less that leads to deposition of more than 200 mcg of the glucocorticoid in the lower portion of the lungs. What is also declared is a method of treating the patient which involves pulmonary administration of the glucocorticoid in the amount of 400 to 4,000 mcg with the aerosol administered by inhalation consisting of three pre-specified periods wherein after the third period, the patient is advised to stop inhaling and exhale; the presented treatment leads to deposition of more than 200 microgram of the glucocorticoid in the lower portion of the lungs.

EFFECT: invention provides improved deposition of the inhaled glucocorticoid in the lower portion of the lungs, min 30% less consumption of oral glucocorticoids and fewer oropharyngeal side effects.

16 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: disclosed is a vesicle-containing composition which is characterised by that it contains: (A) a silicone-based surfactant which is silicon modified with polyoxyalkylene, (B) one or more anionic surfactants selected from polyoxyethylenealkyl(12-15)ether-phosphate, acylmethyltaurate and acylglutamate in amount of 0.001-0.2 wt %, (C) polar oil having IOB of 0.05-0.80 and/or silicone oil, and (D) water, which contains a water-soluble medicinal agent, in amount of 0.5-5 wt % of the weight of the composition, where the silicone-based surfactant (A) forms vesicles; the anionic surfactant(s) (B) is attached to the surface of the vesicles; and the polar oil and/or silicone oil (C) is present inside the bilayer membrane of the vesicles.

EFFECT: disclosed composition has excellent stability even in the presence of high concentrations of a water-soluble medicinal agent.

6 cl, 8 tbl, 10 ex

FIELD: medicine.

SUBSTANCE: agent contains 0.2% Pyriton, an emulsifier, an emollient - isopropyl myristate, and a solvent. The emulsifier is presented by glycerol cocoate PEG-7; the emollient is presented by triglycerides of caprylic and capric acids; the solvent is water. Besides, the agent additionally contains glycerol, cyclomethicone, urea, allantoin and a flavouring agent. All the ingredients of the agent are taken in certain mass ratio.

EFFECT: invention enables eliminating side effects, recovering physiological properties of skin and providing high patient's satisfaction upon completion of the treatment.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: liposomal pharmaceutical composition includes a medicinal substance, lipids in form of phosphatidylcholine and cholesterol, and additionally contains minor positively charged component in form of cetylpyridinium chloride or stearyl ethanolamine.

EFFECT: high bioavailability of the medicinal substance through active transport to body organs and tissue.

10 cl, 3 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine and pharmaceutical industry and describes an inhalation formulation in the form of aerosol for treating bronchial asthma and chronic obstructive pulmonary disease, containing beclomethasone dipropionate, a solvent an adjuvant and a propellant; the solvent is presented by absolute ethyl alcohol, while the adjuvant is an aerosol particle size control consisting of triethyl citrate and perfluorodecaline; the propellant is 1,1,1,4 tetrafluoroethane (HFA-134a) and/or 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea). The formulation has a higher efficacy.

EFFECT: developing the inhalation formulation in the form of aerosol for treating bronchial asthma and chronic obstructive pulmonary disease.

9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a matrix carrier composition for use in a pharmaceutical delivery system for oral administration, which is a suspension consisting of particles of a material in a continuous oil phase. The material consisting of particles comprises a first solid phase comprising silicon dioxide nanoparticles having hydrophobic surface, with particle size of 5-1000 nm, and a second solid phase comprising a biopolymer having hydrophilic and hydrophobic parts, said biopolymer containing polysaccharide. Said continuous oil phase is associated with the first and second solid phases, and the weight of the biopolymer is double that of the silicon dioxide nanoparticles. The invention also relates to a method of producing a matrix carrier composition, which includes mixing a first solid phase comprising silicon dioxide nanoparticles with oil, activating a second solid phase containing polysaccharide, wherein activation includes grinding, vacuum treatment, chemical treatment or ultrasonic treatment, adding said activated second solid phase to the oil and mixing the oil containing the first solid phase and oil containing the activated second solid phase.

EFFECT: improved efficiency and bioavailability of a medicinal agent encapsulated in a matrix carrier.

13 cl, 3 dwg, 1 tbl, 8 ex

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