Dispersible stabilized phospholipid microparticles
The invention relates to the pharmaceutical industry. Quickly dispersible solid dry therapeutic dosage form consists of a water-insoluble compounds, existing in the form of nanoscale or micromeria solid particles, the surface of which is stabilized by a phospholipid, and solid particles dispersed in forming the volume of the matrix. When the dosage form is introduced into the aquatic environment, forming a volume of the matrix is essentially completely dissolved within 2 minutes, thus freeing the particles of water-insoluble solids in the non-aggregated and/or not agglomerated state. Dosage form consists of a water-insoluble substance or therapeutically useful water-insoluble or poorly water-soluble compound, a phospholipid and, optionally, at least one nonionic, anionic, cationic or amphipatic surfactants together with a matrix or forming the volume of the substance and, if necessary, a releasing agent. The volume-weighted average particle size, insoluble in water, is 5 micrometers or less. 9 C.p. f-crystals, 1 table.
This invention also provides methods of cooking dried compositions of particles medicines, water-insoluble or poorly soluble in water, having a composition of modifying the surface of a substance or combination of substances, of which at least one is a phospholipid adsorbed on their surface, and forming a matrix substance. Forming(ie) matrix the substance(s) is(are) sufficient to allow drying from the frozen state, the contact with the aqueous medium. The method includes contacting the above coated with phospholipids particles forming a matrix substance(s) within the period and under conditions sufficient to allow drying frozen particles of drug substance, covered with phospholipids.BACKGROUND of INVENTIONPoor bioavailability of water-insoluble compounds has long been a problem for pharmaceutical production and production of diagnostic tools. While it is believed that compounds with a solubility in water of more than 1% V/o not create problems with bioavailability associated with the dissolution and absorption, many new chemical compounds have a solubility in water significantly below this value (see Pharmaceutical Dosage Forms - Tablets, Vol. 1, page 13. Edited By H. Lieberman, Marcel Dekker, Inc., 1980). Many valuable connections fall out of design, or produce other undesirable manner due to poor solubility in water. A large number of these compounds are unstable in an aqueous environment, and some require dissolution in oil, often making dosage form unpleasant to use or even painful when applied by parenteral administration. This can prevenge, related hospitalizations that were not necessary. There is therefore a need to develop dosage forms with these water-insoluble compounds, which can be dosed in the simplest possible form: rapidly dispersible solid dosage form.There are many ways of cooking quickly dispersible solid dosage drugs. Traditional approaches to this problem involved the dispersion of the biologically active ingredient in a pharmaceutically acceptable fillers with using techniques of mixing and/or granulation methods. Can be applied to specific functional fillers known to the specialists who help the release of a drug, such as fizzy getintegervalue funds, as described in U.S. patent No. 5178878.As a way to improve the disintegration of the solid dosage forms with a release so medicinal substances previously used methods of drying, freezing, which is described in U.S. patent No. 4371516, 4758598, 5272137. In addition, the applied methods of spray drying for such purposes as, for example, in U.S. patent 5776491 in which opisto matrix, forming a composition by spray drying. This matrix is in the form of microparticles quickly desintegrated when placed in an aqueous environment with the release of drug substance. Although these approaches work quickly releasing the medicinal substance solid dosage forms, they suffer a number of disadvantages, particularly those with medicinal substances, which are water-insoluble or poorly soluble in water. In these cases, the suspension of water-insoluble compounds are likely to settle before the completion of the process of freeze drying (lyophilization or spray drying, which leads to aggregation of the particles and, potentially, to obtain inhomogeneous dry dosage forms. In addition, large macromolecules of polysaccharides, typical examples of which include dextrans, when used as auxiliary substances as a shaper of the matrix tended to agglomerate reproduced in suspensions of lyophilized liposomes (Miyajima, 1991). Therefore, the appropriate selection and application of sharidny forming a matrix substances remain difficult, which is obviously related to the physico-chemical nature of the surface under consideration insoluble particles in the water.For example, in U.S. patent 5631023 disclosed is a method of obtaining fast dissolving tablets (10 seconds) with the use of xanthan gum with a maximum weight percentage content of 0.05% as a suspending and flocculonodular substances with gelatin, in which dispersed particles of water-insoluble drugs. As a preferred cryoprotectant used mannitol. The suspension was dried by a freeze in molds to obtain a solid dosage form.In U.S. patent No. 5302401 described method of reducing the growth of particle size during lyophilization. It reveals a composition containing particles has a surface modifier adsorbed on the surface together with cryoprotectants, and cryoprotectant is present in a quantity sufficient to form a composition of cryoprotectant, with the equipment by cryoprotectants is a carbohydrate, such as sucrose. Describes how to obtain particles having the composition of the surface modifier adsorbed on the surface, and the associated cryoprotectant. The patent specifically relates to the composition with 5% of danazol with the addition of 1.5% PVP and sucrose (2%) or mannitol (2%) as cryoprotectant. Thus, although the various cryoprotectant available and properly functioning for the protection of the active substance during freeze-drying, the solid product which is obtained, it is often difficult again dispersing in an aqueous medium.In EP 0193208 described method of freeze-drying latex particles coated with a reagent in order to provide the possibility of playing without aggregation, and discussed the need to include zwitterionic buffer, such as an amino acid, a stabilizer, such as PVP or bovine albumin, and cryoprotectant, such as dextran T10 or other polysaccharide.A BRIEF STATEMENT of the substance of the INVENTIONThis invention is directed to improving the dispersive ability of the pigment micronized particles through specific selection of fillers and methodology necessary to restore the original particles. A characteristic feature of pomerov insoluble or poorly water-soluble compounds. These particles, which are necessary for the practical implementation of the present invention can be obtained by methods disclosed in U.S. patent No. 5091187 and 5091188, as well as in WO 98/07414. In brief water-insoluble or poorly water-soluble compound are dispersed in an aqueous medium in the presence of modifying the surface of substances or combinations of substances, of which at least one is a phospholipid adsorbed on their surface. Fragmentation of particles occurs when the above suspension is subjected to a pressure in the processing using various methods known in the art, including, but not limited to, sonication, grinding, homogenization, microfluidizer, the deposition of antibacterial and solvent. The particles thus obtained, called microparticles, defined here as the solid particles of irregular, non-spherical or spherical shape having a nominal diameter ranging from nanometers to micrometers, which is adsorbed at least one of modifying the surface of substances, one of which is a phospholipid.In accordance with this invention, the suspension of microparticles is) matrix substance(s), present in a quantity sufficient to provide the possibility of freeze drying and subsequent release of drug particles with a surface coating upon contact with an aqueous medium. The choice of these components serves to minimize the tendency of the particles to the formation of aggregates during drying. Such aggregates is extremely difficult to re-atomized due to the very large surface area of the particles, which facilitates the degree of contact necessary for the interaction between particles, resulting in irreversible structure.The small size of the particles of drugs is often required for the development of the dosage form in order to get the maximum possible surface area and bioavailability, but also because of the requirements of solubility. The introduction of the suitable forms of the matrix substance (s) at the above process is used to stabilize the particles of drug substance, covered with phospholipids during freezing and drying the resulting dried product by suppressing any tendency to agglomeration of particles or growth of particles.Description of the INVENTIONThis invention provides fast dezintegrarea the basic particles, stabilized by one or more surface modifiers, including, but not limited to, phospholipids. Examples of some preferred water-insoluble drugs include anti-fungal agents, immunosuppressive and immunostimulatory tools, antiviral agents, anticancer drugs, analgesics and anti-inflammatory agents, antiepileptic agents, antibiotics, anesthetics, hypnotics, sedatives, protivoponosnye tools, neuroleptics, antidepressants, anxiolytics, anti-convulsants, antagonists, neuroblastoma, anticholinergic and cholinomimetic funds antimuskarinovoe act occurs and muskarinovye funds antiadrainergicakimi and antiarrhythmic, antihypertensive agents, hormones and drugs to food. A detailed description of these medicines can be found in Remington's Pharmaceutical Sciences, 18th Edition, 1990, Mack Publishing Co., PA. The concentration of water-insoluble ingredient in aqueous suspensions can range between 0.1 and 60 wt.%, preferably between 5 and 30 wt.%.Water-insoluble compound is first prepared in the form of an aqueous suspension in the presence of one or more surface stabilizing agent is economic phospholipid, including, but not limited to, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, phosphatidic acid, lysophospholipids, egg or soybean phospholipid or a combination thereof. The phospholipid may be a salt or desalted, gidrirovanny or partially gidrirovanny, or natural, semi-synthetic or synthetic. The phospholipid concentration of the ingredient in the aqueous slurry may vary from 0.1 to 90 wt.%, preferably from 0.5 to 50 wt.% and more preferably from 1 to 20 wt.%.Some examples of suitable second and additional surface modifiers include: (a) natural surfactants such as casein, gelatin, natural phospholipids, tragakant, waxes, polymers for Intercollege coating, paraffin wax, gum acacia, gelatin, and cholesterol; (b) nonionic surfactants such as esters and polyoxyethylene fatty alcohols, esters sorbitan and fatty acid esters of polyoxyethylene and fatty acids, sorbitane esters, glycerylmonostearate, polyethylene glycols, cetyl alcohol, cetosteatil alcohol, stearyl alcohol, poloxamer, poloxamine, methylcellulose, hydrocellulose, hydroxyproline surfactants, such as potassium laurate, triethanolamine, sodium lauryl sulfate, alkylpolyoxyethylene, sodium alginate, dioctylsulfosuccinate sodium, negatively charged phospholipids (phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, phosphatidic acid and its salts) and negatively charged glyceriae esters, sodium carboxymethyl cellulose and calcixerollic; (d) cationic surfactants such as Quaternary ammonium compounds, benzylaniline, cetyltrimethylammonium bromide and lauryldimethylamine chloride; (e) colloidal clays such as bentonite and the Whigs (veegum). Detailed descriptions of these surfactants can be found in Remington's Pharmaceutical Sciences, 18th Edition, 1990, Mack Publishing Co., PA and Theory and Practice of Industrial Pharmacy. Lachman et al., 1986. The concentration of additional surfactants in aqueous suspensions may vary in the range between 0.1 and 90 wt.%, preferably between 0.5 and 50 wt.% and more preferably between 1 and 20 wt.%. These surfactants may or may initially be added during mixing, or add them after processing before lyophilization, or a combination of both methods depending on the nature, concentration, and number povehnosti-active substances in the aquatic environment in the process of standard methods of mixing, such as shear, extrusion, cavitation, and/or shaking. Coarse dispersion is a term that defines the mixture for the purposes of this description.Preliminary mixture is then subjected to a process that facilitates the fragmentation of particles, including, but not limited by them, sonication, grinding, homogenization, microfluidizer and deposition by antibacterial and solvent. Time rubbing may vary and depends on the physicochemical properties of the drug, physico-chemical properties of surfactants and selected process of grinding. For example, you can apply the processes of homogenization at high pressure, a typical example of which is the use of equipment such as APV Gaulin E15, Avestin with50 or MFIC Microfluidizer M110EH. During this process the particles in the preliminary mixture is reduced in size at a pressure and temperature that do not degrade significantly the stability of the drug and/or surfactants. Suitable pressure in the processing equal to from about 2000 lb/in2(13790 kPa) up to 30,000 lb/in2(206843 kPa), preferably from about 5000 lb/in2(34474 kPa) up to 20,000 lb/in2(137900 kPa), more predpochtitelno 65S, more preferably from 10 to 45 Celsius. The liquid in the processing circulates through the chamber for homogenization thus, in order to ensure that all the liquid mixture was subjected to discrete homogenization, resulting in a homogeneous suspension of micron or sub-micron particles. Average volumetric size of the suspended particles resulting suspended therapeutic agent is in the interval of 0.05 micrometers and 10 micrometers, preferably between 0.2 micrometers and 5 micrometers, as measured with the use of the instrument based on laser light diffraction Malverm Mastersizer Microplus.The obtained homogeneous suspension of particles, stabilized by one or more surface modifiers, then mixed with forming the matrix increase the volume and/or releasing substances (dry or in aqueous solution) and then dried. Filler or forming a matrix substance is the mass, in which disseminated or stored particles of drug substance. Releasing the tool helps the disintegration of the matrix, when it is in contact with an aqueous medium. Filler/releasing means are selected so as to obtain a carrier matrix to when playing in the aquatic environment. Examples of the forming matrix/releasing means include: (a) saccharides and polysaccharides such as mannitol, trehalose, lactose, sucrose, sorbitol, maltose; (b) humectants, such as glycerin, propylene glycol, polyethylene glycol; (C) natural and synthetic polymers, such as gelatin, dextran, starches, polyvinylpyrrolidone, poloxamer, acrylates; (d) inorganic additives, such as colloidal silicon dioxide, trehosnovnoy calcium phosphate, and (e) polymers based on cellulose, such as microcrystalline cellulose, hydroxymethylcellulose, hydroxypropylcellulose, methylcellulose. Forming a matrix (forming) substances can be added before receiving micronized particles of a therapeutic agent (manufacture of dosage forms) or homogeneous suspension of microparticles before lyophilization. Concentration forming a matrix of substances in aqueous suspensions may vary in the range between 0.1 and 90 wt.%, preferably between 0.5 and 50 wt.% and more preferably between 1 and 20 wt.%.Preferred aqueous slurry may be dried using various methods well known in the art. Among the most traditional methods, spray drying, pocketconsole drying freezing, but this does not imply any limitation. The preferred method of freeze drying lyophilization is, including the sublimation of the frozen water from the aqueous medium of the suspension under reduced pressure. Lyophilization of this suspension can be performed in suitable containers such as glass containers, open trays, tins elements dosage form, or by sputtering in situ on the carrier matrix. For the process of lyophilization, for example, obtained a suspension of microparticles containing form the matrix substance spread on the trays of stainless steel, which is placed on pre-balanced shelves, aged at a temperature equal to 5C, in a sealed chamber with the nominated pressure. The resulting suspension then reduce the temperature With velocity C/min up to-50C, until all of the suspension medium is not fully cured. When this procedure is used only moderate temperature gradients due to the loss of energy between different boundaries (shelf-tray-liquid). As a General rule, the usual time for freezing layer the diluted aqueous slurry thickness of 1 cm is 40-90 minutes at a temperature of-50C. Freezing outside lyophilization camera can on drum cooler, (b) immersion in liquid nitrogen or some other cooling fluid, (C) co-sputtering with liquid CO2or liquid nitrogen, or (d) freezing of the circulating cold air.Separate cooling is necessary to implement a continuous process of freeze drying. Equipment for small granules by instillation of a solution into liquid nitrogen can be purchased in the form of equipment for process Cryopel (Buchmuller and Weyermanns, 1990). Direct freezing inside lyophilization camera provides benefits if the product requires processing under aseptic conditions, which may be in a situation the manufacture of dry injectables.Thus obtained utverzhdennuyu prepared, the suspension is maintained at this temperature over a period of 2 hours to ensure that the crystallization was completed. The pressure inside the chamber is reduced to a pressure equal to approximately 5 mm Od, and preferably up to about 0.1 mm Od. Sublimation of the frozen water is carried out by raising the temperature of the racks of lyophilizate to about-30C - 10S and keeping the material at this temperature for 20 hours until, until the first stage of drying. In the as temperature of sublimation of ice, thermal conductivity of the frozen suspension and the mass transfer coefficient. Other factors, such as temperature or pressure in the chamber can vary considerably. The temperature of the racks can be further enhanced to carry out secondary drying that is considered necessary in accordance with the composition of the sample.Material take after cycle lyophilization to return the camera to room conditions. With the collected dried material may be an operation of the coarse grinding, to facilitate processing or further blending operation with other fillers required to complete obtain the desired solid dosage forms. These fillers may include excipients for tableting and for pressing, which improves slipping substances for encapsulation in gelatin capsules or dispersers for inhalers dry powder.Forming a matrix substance used in this invention should dissolve or dispergirujutsja upon contact with an aqueous medium and release coated phospholipid particles of a therapeutic agent. When playing the product again turns into a suspension having doctitle not more than 10 wt.%, and ideally less than 1 wt.% aggregated primary particles, as shown by the determination of particle size and microscopic methods known in the art. Suddenly what lyophilized suspension obtained according to this invention, can be stored for extended periods of time even under high temperature and humidity without losing this property to registerroutes when playing and, thus, essentially free from aggregation of particles. Lyophilized suspension obtained in accordance with the composition of examples 6-10, it can be stored for at least 60 days at room temperature, which shows the possibility of long-term storage, consistent with a shelf life of pharmaceutical dosage forms.Solid dosage material in this invention is defined as having the property to be easily dispersible. This property is defined as the time required for complete disintegration dried from the frozen state of the precipitate obtained according to this invention, when it is exposed to the water environment, what happens when the introduction of the dosage form in vivo system. The time of disintegration may be the integration of material is placed in water without mechanical mixing, and show the time required to make the material was mainly dispersional by visual observation. In the context of the definition of “fast” it is assumed that the disintegration time is less than 2 minutes, and preferably less than 30 seconds and most preferably less than 10 seconds.The rate of dissolution or release of the active ingredient can also be affected by the nature of the drug and the composition of the microparticles so that it can be fast (5-60 sec) or intermediate (about 75% disintegration after 15 minutes) or slow release.In some cases, visual observation under a microscope or micrograph with scannermodel electron microscope can show the presence of aggregates of particles, but these particles are small and consist of units of the initial particles before lyophilization of the suspension. These units are easily dispersed using low energy levels, such as short periods of treatment with ultrasound or physical mixing, and as such demonstrate the key characteristic of this invention, i.e., preventing the growth of particle size and irreversible aggregation and/or agglomeration.EXAMPLESbannymi in the table. The compositions noted in this table are presented on the basis wt.% dry product. It is clear that the substance of the filler may be added to the suspension before the stage of homogenization or before the stage of drying.Preparations 1 and 2, which are presented in the table above illustrate the fact that these compositions are obtained reproducible particles, showing that a relatively large particle size (about 10 micrometers) exhibit a slight problem from the perspectives of aggregation. These relatively large particles are easily obtained using traditional methods of crushing. However, in order to significantly affect the bioavailability of required particles, the order of smaller than the largest. These particles receive, using the procedures described in U.S. patent No. 5091187 and 5091188 in the form of microcrystals, in WO 98/07414 in the form of microparticles and in U.S. patent 5145684 and 5302401 in the form of nanocrystals. Particles derived from those compositions, which require a special choice of the filler and the processing conditions to achieve particles of the initial suspension. Examples 3 and 5 illustrate that some compositions of microparticles do not play properly when using traditional DL is by these examples, it formed large aggregates consisting of fused primary particles.Examples 6 and 10 illustrate the fact that the particles of the initial suspension easily and quickly reproduced when restoring a suspension of dry powder that does not require intensive mixing. In these examples requires careful selection of the filler, which may also act as cryoprotectant, as well as a humidifier, such as trehalose in the product 8 and mannitol in the product 10.Alternatively, when the sole forms the Foundation of the filler is not suitable, as in the case of sucrose, the composition may include a mixture of fillers selected from pharmaceutically acceptable substances, such as sucrose, trehalose, mannitol, sorbitol or lactose. Examples of drugs 6, 7 and 9 demonstrate this type of composition. Characteristics videoshemale distribution of particle size of drug fenofibrate 6 shown respectively before and after the stage of lyophilization/playback. In this example, the ideal plan of action in order not to change the characteristics of the distribution of particle size after freeze-drying and playback.Without the intention to propose any specific theoretical objasneniiami size particles in freeze-drying/playback using one or more mechanisms, including cryoprotection, the effect of wetting, dispersibility and others.These criteria are unexpectedly important things when trying to restore the suspension of non-aggregated particles after playing a dry dosage form that includes a phospholipid as a surface stabilizer.In addition to the compositions of the examples mentioned above, preparations of this invention can optionally contain suitable quantities sautereau salts and pH regulating the pH of substances, such as sodium hydroxide and/or pharmaceutically acceptable acid. Specialists in the field of chemistry of phospholipids known that at pH below 4 and above 10 phospholipid molecules subjected to intensive hydrolysis. Therefore, the pH of the suspension is usually brought to values within this interval before homogenization. If necessary, the pH may be adjusted before the stage of drying.Although the invention and the examples have been described in connection with what is presently considered the most practical and preferred embodiment, it is necessary to understand that the invention is not limited to the described embodiments, but, on the contrary is intended to cover RA is.
1. Quickly dispersible solid therapeutic dosage form consisting of water-insoluble compounds in the form of nanoscale or micromeria solid particles, the surface of which is stabilized by one or more surface modifiers, of which at least one may be a phospholipid, solid particles dispersed in creating the volume of the matrix, also optionally including releasing substance, forming dosage therapeutic form during drying, and when the dosage form is introduced into the aquatic environment, forming a volume/releasing matrix, essentially fully desintegrated within less than 2 min, thus freeing the particles of water-insoluble solids in the non-aggregated and/or not agglomerated state.2. Quickly dispersible solid dosage form under item 1, comprising particles of a therapeutically active water-insoluble or poorly water-soluble compound, a phospholipid and, optionally, at least one nonionic, anionic, cationic or amphipatic surfactant, in which the volume-weighted average particle size of water-insoluble substances compiled by the HT forming volume/releasing matrix is selected from saccharides, polysaccharides, moisturizers, natural or synthetic polymers, inorganic additives or polymers based on cellulose.4. Quickly dispersible solid dosage form under item 3, in which the saccharide or polysaccharide is mannitol, trehalose, lactose, sucrose, sorbitol or maltose.5. Quickly dispersible solid dosage form under item 3, in which the humectant is glycerin, propylene glycol or polyethylene glycol.6. Quickly dispersible solid dosage form under item 3, in which natural or synthetic polymer is gelatin, dextran, starch, polyvinylpyrrolidone, poloxamer or acrylate.7. Quickly dispersible solid dosage form under item 3, in which the inorganic additive is colloidal silicon dioxide or trehosnovnoy calcium phosphate.8. Quickly dispersible solid dosage form under item 3, in which the polymer based on cellulose is microcrystalline cellulose, hydroxymethylcellulose, hydroxypropylcellulose or methylcellulose.9. Quickly dispersible solid dosage form under item 1, for which the disintegration time in water is less than 2 min, the pre is quickly dispersible solid dosage form under item 1, optionally containing effervescent agent, binding agent, flavoring, polymer coating on the outer surface of the dosage form, coloring matter or a combination thereof.
The invention relates to lyophilizate with increased dissolution rate, which can be restored without the formation of particles, which is achieved by re-heating of selected solutions in bottles to a temperature of from 30 to 95With directly in the freeze-dryer for 10 min to 4 h
The invention relates to the field of pharmaceutical industry and relates to lyophilized peptide/lipid product
The invention relates to medicine, namely to a restorative or cosmetic surgery and aesthetic dermatology
The invention relates to medicine and relates to pharmaceutical compositions containing a nucleotide analog, mannitol and modifying additive, which is sodium chloride or a polyol suitable for freeze-drying
The invention relates to medicine and sustainable, not containing albumin preparation of recombinant Factor VIII (rFVIII) in dried form, which has both crystalline and amorphous components, which after dilution water contains from about 65 to 400 mm glycine, 50 mm histidine, from 15 to 60 mm sucrose, 1 to 50 mm sodium chloride, 5 mm calcium chloride and from 50 to 1500 IU/ml rFVIII
The invention relates to compositions in the form of microcapsules or implants
The invention relates to the production of antibiotics, namely the technology of water-soluble salts of erythromycin, erythromycin phosphate
The invention relates to a method of stabilization and regulation changes in the peptide includes the sequence-Asp-Gly - or-Asn-Gly in the amino acid sequence in which the sequence-Asp-Gly - or-Asn-Gly - change operations on the fragment using a dehydration reaction or reactions desametasone and subsequent changes in-rearranged fragment using isomerization reactions, in particular, by way of regulation of such changes in the peptide, such as desulfuromonas hirudin or genuinely option
The invention relates to new solid or semi-solid pharmaceutical compositions containing soluble and capable of forming a gel salt of a peptide having an increased specific surface
The invention relates to medicine, namely to wound healing tools, and can be used for treatment of burns
The invention relates to the production of fine powders of drugs suitable for inhalation
The invention relates to medicine, namely to the development of new dosage forms for oral administration
The invention relates to the field of pharmaceutical industry and relates to improved pharmaceutical compositions for oral administration containing substituted pyridinesulfonamide and a carrier comprising a polymer with vinylpyrrolidone links or a copolymer of vinylpyrrolidone and vinyl acetate, located mainly in the form of a capsule, coated, containing a mixture of substituted pyridinesulfonamide and polymer
The invention relates to medicine, in particular to pharmacological agents and treatment joints
Centuries-old medical experience shows that virtually every man occasionally pain in the back and joints of the limbs (Nordemar P
The invention relates to pharmacy
The invention relates to pharmaceutical industry and relates to solid dosage forms prolongirovannogo steps and the method of obtaining
FIELD: medicine, gastroenterology.
SUBSTANCE: one should apply food additives as tablets of oats, corn and cabbage by "Biophyt" company; moreover, to decrease motor system of biliary ducts one should apply tablets of oats, to increase motor system - tablets of corn and for total normalization of kinetics - tablets of cabbage. Treatment lasts for 10 d at the dosage of 1-2 tablets twice daily 30 min meals. The present innovation enables to normalize functional activity of biliary ducts at the background of shortened therapeutic terms.
EFFECT: higher efficiency of therapy.