Stable medicinal agent and method for its making
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a new composition of benzimidazole (omeprazole) and a method for its preparing. The benzimidazole composition comprises a benzimidazole compound in common with compound with acid reaction and includes inert core with applied benzimidazole, inert and external layer having enteral coating, pH 6.6-6.95. Also, invention relates to a method for preparing the composition wherein layers are applied in a device used for applying coatings in moving layer. Proposed compositions elicit the enhanced stability and biological availability.
EFFECT: improved and valuable pharmaceutical properties of compositions.
15 cl, 2 ex
The technical field
The invention relates to a new galenical composition benzimidazole, in particular omeprazole or similar compound, which is stable, although not contains compounds, which give an alkaline reaction, but involves a join, giving an acid reaction in contact with benzimidazole. The invention also concerns the method of making such a composition.
The level of technology
In General, it is considered that the benzimidazole, such as omeprazole, are not stable in an acidic environment and therefore herbal compositions containing such benzimidazol must contain the connection, which gives an alkaline reaction. An example of such compositions described in the patent EP-A 0247983.
Through a combination of benzimidazole with a sufficient number of connections, giving an alkaline reaction, can be obtained herbal composition having very good resistance. These herbal compositions, however, have inherent problems. For example, enteric coating compositions are acidic group capable to react with the compound of the kernel, which gives an alkaline reaction. It is well known that the core, giving an alkaline reaction, it is necessary to separate from the enteric coating of the intermediate layer, and therefore in the process of manufacturing such galenical compositions have very carefully to fit the thickness and type of the intermediate layer, as well as enteric coating to the alkalinity of the core in order to obtain the galenical composition with sufficient stability and good bioavailability. Such problems are considered, for example, in example 1 of patent EP-A 0247983.
Not so long ago developed some compositions, in which the benzimidazole is not used in combination with the connection, which gives an alkaline reaction. An example of this development is described in the patent US-A 5626875 and, respectively, in EP-A 0773025. This patent discloses a composition containing:
- inert core,
is covered with the first layer comprising benzimidazole together with a water-soluble polymer,
another layer comprising a water-soluble polymer and
- enteric coating.
In the examples of this patent, the benzimidazole is used in composition with auxiliary substances, which, in General, are considered to be inert, such as with talc. However, the talc in the pharmaceutical may contain impurities, and when measuring the pH value in the suspension of talc in water it often has a value greater than 7 (the technique of "ISFET" or phenol red indicator).
In some recently developed drugs, containing omeprazole, to improve the stability of the medicinal product omeprazole is used in conjunction with a specific stabilizer, for example, mannitol the (ER-AND 646006), TiO2(WO 96/37195), cyclodextrins (WO 98/40069) or amino acids. However, it would be desirable to have alprazolamabuse drug resistant enough without such stabilizer.
There is a need for medicines containing benzimidazole compounds, in particular omeprazole or similar connection, as biologically active substances that would have an exceptional stability in combination with good bioavailability and had no problems and disadvantages of certain drugs prior art.
This invention is based on the surprising conclusion, which is that the benzimidazole, which was considered to be very unstable to acids actually have exceptional resistance to their use in compositions together with the connection, the pH of which is less than 7 when it is aimed at measuring the pH value is put into contact with a sufficient amount of water (connection, giving an acid reaction, the acidic substance).
Thus, in accordance with this invention creates a sustainable drug for oral administration containing a benzimidazole compound of the formula I
where R1 represents hydrogen, methoxy or gift is methoxy, R2 is hydrogen, methyl or methoxy, R3 is methoxy, 2,2,2-triptoreline or 3-methoxypropane and R4 is hydrogen, methyl or methoxy,
(a) an inert core,
(b) on the layer of biologically active compounds containing benzimidazole compound of formula I in a mixture with the compound, which gives an acid reaction, and, if necessary, with pharmaceutically compatible auxiliary components
(C) at least one inert layer and
(g) the outer layer deposited on the inert layer and having an enteric coating.
According to the invention it is also proposed a method of manufacturing the drugs, including the following techniques:
(i) the manufacture of an inert core,
(ii) application of benzimidazole layer on the inert core,
(iii) applying one or more inert layers
(iv) the application of the enteric coating.
The benzimidazole of formula I are well known as effective inhibitors of allocation of acid gastric juice. Typical examples of such compounds of benzimidazole are omeprazole, lanzoprazol and pantoprazole. Most preferred is omeprazole.
The inert core is preferably a known sugar or starch kernel. This inert core coated with benzimidazole layer. Benzimidazole layer contains biologically asset is th substance - the benzimidazole - in combination with the connection, giving an acid reaction. May also be present and pharmaceutically compatible auxiliary substances. In General benzimidazole layer as a binder will contain a water-soluble polymer (preferably non-alkaline), which is explained below.
Benzimidazole layer is supplied with an inert coating that separates the first floor, containing benzimidazole, from enteric coatings. Inert coating in General contains a water-soluble polymer and, if necessary, other pharmaceutically compatible auxiliary substances.
Preferably, the pH-value of aqueous suspension or solution obtained from the inert coating is about $ 7. If there are two inert coating, in this case, the pH value of aqueous suspension or solution of the first inert coating is less than the pH of the aqueous suspension or solution of the second inert coating.
Preferably, there were at least two inert coating (or layer; "layer" and "coating" are used in this description are synonymous). The first inert coating generally contains a water-soluble polymer, preferably non-alkali, if necessary, the compound that gives an acid reaction, and, if necessary, pharmaceutically compatible auxiliary ve is esta. The second inert coating applied between the first inert coating and enteric coating typically comprises a water-soluble polymer, preferably non-alkali, if necessary, the compound that gives an acid reaction, and, if necessary, pharmaceutically compatible auxiliary substances. The second inert coating and the first inert coating preferably have different compositions.
The first inert coating (if any) serves as a barrier between the active benzimidazole layer and the second inert coating, which can contain components that must not come into contact with benzimidazole layer. This first layer usually contains a water-soluble polymer, predominantly connection, giving an acid reaction, and conventional excipients, such as, for example, grease. As lubricants are preferred poliatilenglikola, known as poloxamer.
The second inert layer is an intermediate layer between the enteric coating and the inner part of the preparation. It usually includes a water-soluble polymer and normally free from connection, giving an acid reaction (although it may include it). Further, this layer may contain conventional excipients, such as talc and pigments, for example titanium dioxide.
If tol is to one inert layer, it usually has the same composition as described above, the second inert layer.
Enteric layer serves classic enteric coating. It contains the usual enteric substances known in the prior art, such as phthalates, cellulose and type copolymers of methacrylic acid, such as methacrylic acid alkyl ester of (meth)acrylic acid, commercially available under the trademark Eudragit®. As the alkyl residue preferred methyl and ethyl group.
Preferred is a copolymer based on methacrylic acid type With the USP. Especially preferred product Eudragit L30D55. The preferred polymer is a copolymer based on methacrylic acid and ethyl ester of acrylic acid. The formula is as follows:
The ratio of free carboxyl groups and ester groups is approximately 1:1. The average molecular weight is, for example, about 250,000.
This copolymer will be easy to dissolve at pH values above 5.5 with formation of salts.
Triethylcitrate and/or polyethylene glycol or similar compounds can be used in enteric coating as plasticizers. May be present and talc. Also there may be other conventional auxiliary substances.
The content is ameesha in medicinal products according to the invention the connection, giving an acid reaction are not particularly limited. This connection is determined by the fact that when suspendirovanie or dissolved in water, its pH is less than 7.
Used for coating the aqueous mixture containing the benzimidazole and the connection, which gives an acid reaction should, in particular, to have a pH value less than 7, preferably in the range from 6.5 to 6.95, even more preferably in the range from 6.6 to 6,95.
In accordance with this, the layer containing omeprazole and connection, giving an acid reaction, when it should suspendirovanie in the water to have a pH value less than 7. Material layer in the amount of 5-50 mg, suspendirovanie 100 mg water should have a pH value mainly in the range from 6.5 to 6.95, preferably from 6,6 to 6.95. Measurement of the pH value preferably immediately after the suspension of the material layer in the water. "Directly" means in this context, the period of time within 30 minutes, preferably within 5 minutes, after the material was placed in water. For practical reasons, it is rational to measure the pH value in solution or suspension containing an inert core with the layer comprising benzimidazole. If the measurement is performed in the presence of an inert core, it is especially important to carry out this measurement directly (preferably as soon as possible after the AK material was placed in water, to avoid the risk of dissolution of the core material and its influence on the pH value. In particular, it is not necessary to grind the core, allowing the core material to dissolve as slowly as possible.
If inert coating contains a compound which gives an acid reaction, the pH value of the solution or suspension of an inert coating should be less than 7, while preferably 5-50 mg of coating material suspended or dissolved in 100 ml of water, had a pH value between 6.5 to 6.95, preferably in the range from 6.6 to 6,95.
How is the measurement of pH is not critical, but preferred is a well-known technology "ISFET" using ISFET electrode. If otherwise is not specified, pH measurement, referenced herein, were made using the technology "ISFET" at a temperature of 25°C.
Connection, giving an acid reaction, preferably represents a sodium dihydrophosphate (NaH2PO4), whereby there were obtained the best results with respect to sustainability. The number of connections, giving an acid reaction, is determined by the desired pH value.
Connection, giving an acid reaction, be sure to include a layer containing a benzimidazole, and preferably has an inert layer. If there are two inert layer (preference is sustained fashion form of execution), the connection, which gives an acid reaction, preferably is present in the first inert layer and preferably is missing in the second inert layer.
Water-soluble polymer is generally present in benzimidazole layer in an inert layer (inert layer acts as a binder and may be any polymer known that it is water soluble and quickly dissolves in water. You can apply the same polymer in all layers, where it is provided, or use a different water-soluble polymers in different layers. Preferred water-soluble polymers are non-alkaline water-soluble polymers, especially preferred hydroxypropylmethyl-cellulose and hydroxypropylcellulose.
Conventional pharmaceutically compatible auxiliary substances known to the expert can be present in any layer of the medicinal product. These excipients in an aqueous solution or suspension preferably have a pH of about 7 (e.g., from 5 to 9). The type and amount of these auxiliary substances can be easily determined by the expert based on his special knowledge.
If otherwise is not specified, excipients include conventional binders, plasticizers, dyes, pigments, such as titanium dioxide, talc and other Izv the local auxiliary substances.
This invention eliminates the need for the layer containing a benzimidazole, contained specific stabilizer benzimidazole as described in the prior art for some drugs, such as mannitol (EP-A 646006), TiO2(WO 96/37195) or cyclodextrins (WO 98/40069) or amino acids. Moreover, it is preferable that the layer containing a benzimidazole, had only a benzimidazole, a binder and a compound, which gives an acid reaction.
Especially preferred drug of the present invention is a composition in the form of granules, including:
(a) an inert core, representing sugar or starch nucleus
(b) coated with a mixture of omeprazole, hydroxypropylmethylcellulose and such amount of sodium dihydrophosphate that 5-50 mg of coating material suspended or dissolved in 100 ml of water, have a pH between 6.5 to 6.95, preferably in the range from 6.6 to 6,95,
(C) a first inert coating on alprazolamabuse layer, with the first inert coating is composed mainly of hydroxypropylmethylcellulose, polyethylenepolypropylene and such amount of sodium dihydrophosphate that 5-50 mg of coating material in 100 ml of water have a pH between 6.5 to 6.95, preferably in the range from 6.6 to 6,95,
(g) the second trade is Noah floor, deposited on the first inert coating, while the second inert coating is composed mainly of hydroxypropylmethylcellulose, talc and titanium dioxide, and
(d) an outer layer deposited on the second inert coating consisting mainly of a copolymer of methacrylic acid with alkyl ether (meth)acrylic acid, triethylcitrate and talc.
Also preferably, the pill, having only an inert core and a coating containing a benzimidazole, when it suspendirovanie 4 ál deionizovanoy water had a pH ranging from 6.6 to 6,95. If there are two or more inert layers also preferably, the pill, having only an inert core, a coating containing a benzimidazole, and the first inert coating, when it is suspendirovanie 4 ál of deionized water had a pH ranging from 6.6 to 6,95. Also, it is preferable to measure pH directly after the material is placed in water in order to minimize the possible influence of the inert cores (within 30 minutes, preferably within 5 min after the material was placed in water).
Medicines according to this invention can be produced by known methods. Methods of coating are conducted mainly in device for coating a moving layer. Drug creditbalance the invention have the form of pills, and the final dosage form intended for reception by the patient, is a capsule, including the pill. Alternatively, it is also possible to press pills in pills.
Preferably between meals on the coating was carried out stages of drying, which, of course, it is not necessary. When conducting stage of drying is not required to interrupt the process in the moving layer (that is, the drying operation can be carried out in a moving layer), but the spray drying process should, of course, stop. In case of carrying out the drying phase of its duration is approximately 10-20 minutes.
The following examples explain the invention, but not limit it.
Prepare the dispersion of 140 g of deionized water, 20 g of omeprazole and 16 g of hydroxypropylmethylcellulose. The pH of this dispersion with water of 0.5-molar solution of sodium dihydrophosphate set equal 6,65. The pH value is measured ISFET electrode. Prepared by suspension coated on 140 g of neutral pellets in a device for coating a moving layer.
Suspension for inert coating is prepared by dispersing 125 g of deionized water, 3 g of titanium dioxide, 5 g of talc and 15 g of hydroxypropylmethylcellulose. This suspension is applied on the pill omeprazolum the opening in the device for coating a moving layer.
On manufactured so pills known cause enteric coating. Suspension enteric coating prepared from 30 g of a copolymer based on methacrylic acid type (according to USP), 12 g of talc, 4.5 g of triethylcitrate and 95,0 g of deionized water. Again use the device for coating a moving layer.
Thus obtained granules are sustainable and provide exceptional bioavailability.
Repeating example 1 with the only difference that after applying alprazolamdosage layer on the inert core is primarily inflicted the first surface treatment. Was used for this solution for a coating prepared from 5 g of hydroxypropylmethylcellulose, 1.0 g poloxamer 188, 40 g of deionized water and water of 0.5-molar solution of sodium dihydrophosphate to install a pH approximately equal to 6.9. The coating was applied in a device for coating a moving layer. On this first inert coating then applied the following inert coating (second inert coating and enteric coating, using the same components, amounts and techniques described above in example 1.
Thus obtained granules have a high resistance and exceptional bioavailability.
When the frame is x this application tells what 5-50 mg of coating material or layer give 100 mg of water a pH value within certain limits, this by itself means that to perform sign enough that any amount of the specified range of 5 to 50 mg per 100 mg of water gave a pH value within a certain range. Thus, to perform this characteristic is sufficient, for example, if 5 g of the material layer 100 mg water to give a pH value within a certain range, even if a different number of material layers, for example, 10 mg of the material layer (or 50 mg of the material layer), 100 mg of water will give a pH value lying outside a certain range.
1. The drug is in the form of pills for oral administration, containing a benzimidazole compound of the formula I
where R1represents hydrogen, methoxy or deformedarse;
R2is hydrogen, methyl or methoxy;
R3- methoxy, 2,2,2-triptoreline or 3-methoxypropane;
R4is hydrogen, methyl or methoxy,
includes (a) an inert core, (b) on the layer of biologically active compounds containing benzimidazole compound of formula I in a mixture with the compound, which gives an acid reaction, and, if necessary, with pharmaceutically compatible auxiliary components, (b) at least one inert the layer, and (g) the outer layer, deposited on inert layer and having an enteric coating.
2. The drug according to claim 1, in which the first inert layer deposited on the layer of biologically active substances, and the second inert layer deposited on the first inert layer.
3. The drug according to claim 2, in which the first inert layer comprises an inert water-soluble polymer, if necessary, the compound that gives an acid reaction, and, if necessary, pharmaceutically compatible auxiliary substances, and the second inert layer includes a water-soluble polymer and, if necessary, pharmaceutically compatible auxiliary substances.
4. The drug according to claim 3, in which the first inert layer includes the compound that gives an acid reaction.
5. The drug according to claim 4, in which connection, giving an acid reaction, is a sodium dihydrophosphate.
6. The drug according to claim 3, in which the water-soluble polymer is a hypromellose and/or hydroxypropylcellulose.
7. The drug according to claim 1, in which the suspension of an inert core and a layer of biologically active substances of the pill in 4 μl water has a pH in the range of 6.5-6,95, in particular 6,6-6,95.
8. The drug according to claim 1, in which the layer of biologically active substances and the first inert layer, if the n is available, free from talc.
9. The drug according to claim 1, in which the benzimidazole compound of formula I is a omeprazole.
10. The drug according to claim 1, comprising (a) an inert core, (b) on the layer of biologically active substances, consisting mainly of omeprazole, hydroxypropylmethylcellulose and connections, giving an acid reaction, in this connection, giving an acid reaction, is the amount at which the suspension inert layer with a layer of biologically active substances in 4 μl water has a pH in the range of 6.6-6,95 (in) of the first inert layer consisting mainly of hydroxypropylmethylcellulose, connections, giving an acid reaction, and grease (g) a second inert layer consisting mainly of hydroxypropylmethylcellulose, talc and pigment, in particular TiO2(d) an outer layer consisting mainly of enteric coating formed from a copolymer of methacrylic acid with alkyl ether (meth)acrylic acid, triethylcitrate and talc.
11. The drug of claim 10, in which connection, giving an acid reaction, is a sodium dihydrophosphate.
12. A method of manufacturing a medicinal product, including the following techniques: (i) the manufacture of an inert core, (ii) a coating on an inert core suspension containing benzimidazole compound Faure the uly I, and the connection giving an acid reaction, and having a pH within the 6.5-6,95, in particular 6,6-6,95, (iii) applying at least one inert layer, (iv) an enteric coating layer.
13. The method according to item 12, which includes the following techniques: (i) the manufacture of an inert core, (ii) a coating on an inert core suspension containing benzimidazole compound of formula I and the compound, which gives an acid reaction, and having a pH within the 6.5-6,95, in particular 6,6-6,95, (iii) applying the first inert layer, (iv) applying a second inert layer and (v) an enteric coating layer.
14. The method according to item 13, in which the first inert layer is applied from a coating solution or suspension of the coating, having a pH in the range of 6.5-6,95, in particular in the range of 6.6-6,95.
15. The method according to one of PP-14, in which the layers are applied by means of a device for coating a moving layer.
FIELD: medicine, pharmacy.
SUBSTANCE: invention concerns a pharmaceutical composition eliciting hepatoprotective effect. The base of pharmaceutical composition comprises adducts of orotic acid with amino acids or amines as an active substance. The composition comprises effective amount of active substance and special additives in the following ratio of active substance and special additives, wt.-%: active substance, 0.05-40.0; special additives, 60.0-99.95. As special additives the composition comprises starch, mixture of vitamins, lactose, aerosil, talc, stearates, polyvinylpyrrolidone, solid confectionary fat, Tween-80, polyethylene glycol, glycerol, citric acid, benzoic acid, sodium benzoate, correcting dye-substances. Compositions are made as tablets, capsules, lozenges, suppositories, syrups. Also, invention proposes a medicinal agent comprising above said pharmaceutical composition. Invention provides high pharmaco-therapeutical effect with fitness period 2 years, not less.
EFFECT: improved and valuable pharmaceutical properties of composition.
9 cl, 6 tbl, 8 ex
FIELD: pharmaceutical industry.
SUBSTANCE: preparation method comprises heating rock oleoresin to specified temperature, forming tape by passing through rolls, and tableting in laminar air flow using, for example, tubular knife with cutting edge sharpening radius no greater than 0.2 mm.
EFFECT: enabled tableting in absence of inert additives at any temperature and moisture characteristics of atmospheric air and enhanced therapeutical effect of rock oleoresin tablets.
2 cl, 3 tbl, 3 ex
FIELD: medicine, cardiology, pharmacy.
SUBSTANCE: invention relates to pharmaceutical composition comprising atenolol as an active component and additives - starch, magnesium basic carbonate, polyvinylpyrrolidone and/or starch glycolate sodium salt, gelatin and stearate; or starch, polyvinylpyrrolidone, stearate, aerosil and microcrystalline cellulose. Composition shows improved physical-mechanical properties.
EFFECT: improved pharmaceutical properties of composition.
14 cl, 1 tbl, 5 ex
FIELD: medicine, oncology, chemical-pharmaceutical industry and technology, pharmacy.
SUBSTANCE: tablet with antitumor effect contains acceptable carrier on which the following mixture of aqueous-alcoholic tinctures is applied: bloody geranium, penny-cress, common cocklebur and European wild ginger. Tablets by mass 1 g including slipping substance contains the following amounts of indicated tinctures as measure for dry matters, g: bloody geranium, 0.015-0.020; penny-cress, 0.011-0.015; common cocklebur, 0.011-0.017, and European wild ginger, 0.024-0.036. Method for preparing tablet involves applying on carrier the mixture of aqueous-alcoholic tinctures of above indicated plants, the following drying the prepared mass, its granulating and tableting. Method for prophylaxis and treatment of oncological patients involves prescription 0.5-2 tablets with oncological designation, tree times per a day and the treatment course is determined individually based on objective data of treatment. Tablet made by claimed methods shows complex properties: it delays tumor growth and metastazing and can be recommended for treatment and prophylaxis of oncological pathology both independently and in combination with chemo-radiation therapy. Invention can be used in technology for making medicinal formulations of preparations with oncological designation and for treatment of patients with oncological pathology of different organs and body systems.
EFFECT: improved for making tablet, valuable medicinal properties of tablet.
7 cl, 4 ex
FIELD: medicine, oncology, chemical-pharmaceutical technology, pharmacology, pharmacy.
SUBSTANCE: tablet eliciting the antitumor effect comprises active dose of aconite alkaloids in the amount 0.0125-0.0375 mg. Invention relates to a method for making tablet with antitumor effect. Method involves treatment suitable carrier taken in the amount corresponding to the content of alkaloids in tablet 0.0125-0.0375 mg with aconite tincture wherein amount of the total content of alkaloids is determined preliminary. Then carrier treated by such manner is dried at temperature 30-35°C, not above, granulated, granules are powdered and tableted. Also, invention relates to a method for treatment of oncological patients that involves prescription to patient 0.5-2 tablets with oncological designation being this treatment is determined individually. Invention can be used in manufacturing medicinal formulations of preparations used for treatment of patients with oncological pathology.
EFFECT: improved method for treatment and making, valuable medicinal properties of tablet.
8 cl, 2 ex
SUBSTANCE: invention relates to films for in-mouth application containing cosmetic or pharmaceutical substances. Film comprises at least one water-soluble polymer such as pullulan, pharmaceutically active agent, and ion-exchange resin as taste masking agents containing divinylbenzene-crosslinked polystyrene. Preparation procedure: water-soluble ingredients are dissolved in water; water-soluble film-forming agent is mixed with one stabilizer to form film-forming mixture; the latter is combined with above aqueous solution and resulting mixture is stirred to form gel; gel is mixed with oil blend to give homogenous gel, which is poured onto support and dried to form desired film.
EFFECT: achieved good masking of agent taste and good-quality appearance.
28 cl, 7 tbl, 7 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to the solid medicinal formulation comprising chondroitin sulfate. The proposed medicinal formulation comprises 250 mg of chondroitin sulfate as an active component, filling agent, binding agent, antifriction substances and can comprise a solubilizing agent additionally. Pharmaceutical composition is made as a tablet. Invention provides development of the preparation for oral administration with the less amount of active substance and with indices satisfying requirements of the State Pharmacopoeia.
EFFECT: improved and valuable properties of formulation.
8 cl, 16 tbl, 39 ex
FIELD: medicine, pharmacology, pharmacy.
SUBSTANCE: antiviral agent comprises aciclovir as an active substance and special additives wherein agent comprises potato starch, talc, stearic acid or stearates as special additives taken in the definite ratio of components. Antiviral agent is made as a tablet. Also, invention relates to a simple method for preparing an antiviral agent and invention provides rapid release of active component. Invention can be used for treatment of skin and mucosa viral diseases induced by herpes simplex virus or herpes zoster virus, and for prophylaxis of these diseases in patients with damage of the immune system.
EFFECT: improved method for preparing, valuable medicinal properties of agent.
4 cl, 1 tbl
FIELD: medicine, chemical-pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to producing a medicinal preparation with analgesic, antipyretic and anti-inflammatory effect. The preparation is made as a tablet comprising a core containing ibuprofen as an active substance wherein a core is covered by envelope masking taste of the preparation. Core comprises potato starch and calcium stearate as special additives, and envelope comprises sugar, magnesium basic carbonate, polyvinylpyrrolidone, aerosil, talc, titanium dioxide, gelatin, vanillin, dye acid red and bee wax. Invention provides the necessary quality and necessary therapeutic effect of tablets due to rapid release of active substance from the tablet core wherein the core decomposition is 7-8 min and that in dissolving and 92-94% of active component transfers to medium in 45 min.
EFFECT: improved method for preparing, improved and valuable medicinal and pharmaceutical properties of preparation.
4 cl, 1 tbl, 5 ex
FIELD: medicine, gastroenterology, pharmacy.
SUBSTANCE: invention relates to a solid composition eliciting with an anti-ulcer activity and to a method for its preparing. Pharmaceutical composition consists of a core containing famotidine as an active component and starch, aerosil, stearic acid salt as accessory inert substances wherein a core is covered by polymeric envelope. Core comprises glucose and stearic acid as an accessory inert substance and magnesium stearate as a stearic acid salt. Polymeric envelope comprises oxypropylmethylcellulose, propylene glycol, castor oil, talc and titanium dioxide taken in the definite ratio of all components in the composition. Method for preparing pharmaceutical composition involves preparing raw, mixing therapeutically effective amount of famotidine with glucose and starch, moistening the mixture with starch paste, granulation, drying wetted granulate, repeated granulation, powdering dry granules, tableting and applying polymeric envelope containing oxypropylmethylcellulose on prepared cores with addition of titanium dioxide, propylene glycol, castor oil and talc. Invention provides enhancement of degradability, solubility and stability in storing.
EFFECT: improved method for preparing, valuable pharmaceutical properties of composition.
3 cl, 1 ex
FIELD: veterinary science.
SUBSTANCE: one should apply combined introduction of T-activin at the dosage of 5 mcg/kg once daily along with a single introduction of phenbendasol at the dosage of 5 mg/kg. Moreover, T-activin should be introduced for 3 d, and phenbendasol should be introduced simultaneously with the last injection of T-activin. Conditions for injecting immunomodulating agent and certain sequence of its injection along with antihelminthic preparation provide increased resistance to repeated infectioning in animals.
EFFECT: higher efficiency of combined therapy.
2 ex, 2 tbl
FIELD: medicine, gastroenterology.
SUBSTANCE: traditional eradication therapy should be supplemented with licopid at the dosage of 10 mg per os once daily before breakfast for 10 d. The present innovation prevents transfer of microorganisms into inactive form, accelerates restoration of mucosal epithelial layer in gastroduodenal area, provides complete eradication of microorganisms, that in its turn, favors to prevent disease exacerbation and restoration of gastroduodenal functions.
EFFECT: higher efficiency of therapy.
3 dwg, 2 ex
FIELD: pharmaceutical industry.
SUBSTANCE: rectal- and vaginal-administration suppositories contain 1,3-diethylbenzimidazolium triiodide as active principal, polyvinylpyrrolidone as solubilizer and stabilizer, and lipophilic base with specified proportions of components.
EFFECT: extended therapeutical activity and reduced occurrence of side effects.
4 cl, 2 ex
FIELD: organic chemistry, chemical technology, pharmacy.
SUBSTANCE: invention relates to new spiroimidazolidine derivatives of the formula (1):
wherein R1 represents hydrogen atom or methyl; R2 represents phenyl or (C1-C4)-alkyl; X represents -CH2-CH2- or -CH2-CH2-CH2-; W represents isopropyl or cyclopropyl; V represents hydrogen atom or methoxy-group; E represents -CO-R3 wherein R3 represents hydroxy-group, (C1-C4)-alkoxy- or amino-group; phenyl represents unsubstituted phenyl residue or phenyl residue substituted with one or some similar or different substitutes taken among the group consisting of (C1-C4)-alkoxy-, methylenedioxy- and ethylenedioxy-group in all its stereoisomeric forms and their mixtures in all ratios, and to its physiologically acceptablesalts. Also, invention relates to a method for preparing compounds of the formula (1) and pharmaceutical composition based on these compounds. Invention provides preparing new compounds eliciting the inhibitory effect with respect o leukocytes adhesion.
EFFECT: improved preparing method, valuable medicinal properties of compounds.
16 cl, 1 tbl, 41 ex
FIELD: organic chemistry, pharmacy.
SUBSTANCE: invention relates to new derivatives of benzimidazole represented by the following formula (I) or its salt:
wherein R1 represents (lower)-alkyl group; R2 represents aromatic (lower)-alkyl group that can be substituted with one or more groups taken among halogen atom, alkyl group, halogen-(lower)-alkyl group, nitro-group, aromatic group, aromatic (lower)-alkoxy-group, (lower)-cycloalkyloxy-(lower)-alkyl group, aromatic (lower)-alkyl group, aromatic (lower)-alkenyl group, aromatic (lower)-alkynyl group, aromatic oxy-(lower)-alkyl group, (lower)-cycloalkyl-(lower)-alkoxy-group, alkenyl group, (lower)-alkoxy-group, (lower)-alkylthio-group and (lower)-alkanesulfonylcarbamoyl group; R3 represents alkyl group, hydroxy-(lower)-alkyl group, alkenyl group, aromatic group, halogenated aromatic group, (lower)-alkyl aromatic group, (lower)-alkenyl aromatic group or aromatic (lower)-alkenyl group; -X- represents cross-linking group represented by one of the following formulas: (II) , (III) , (IV) , (V) . Also, invention relates to pharmaceutical compositions eliciting activity that reduces blood glucose level based on this compound. Invention provides preparing new compounds and pharmaceutical compositions based on thereof used for prophylaxis and treatment of damaged tolerance to glucose, diabetes mellitus, insulin-resistance syndrome, vascular failures syndrome, hyperlipidemia and cardiovascular disorders.
EFFECT: valuable medicinal properties of compounds and compositions.
16 cl, 1 tbl, 86 ex
or its pharmaceutically acceptable salt, where Rrepresents a group of formula -(ALK)q-R1where (ALK) represents alkyl, alkenyl or quinil, q is 0 or 1, R1represents a group of formula-CO2R2where R2is hydroxyalkyl, alkoxyalkyl or toolboxitem, Rrepresents a group of the formula
where o is 0 or 1, n is 0, 1 or 2, X represents N or CH, Y is O, NR11or CHR11where R11represents hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, carboxyl, or acyl, or a group of the formula -(alkyl)p-CN, -(alkyl)p-aryl, -(alkyl)p-O-aryl, -(alkyl)p-O-aralkyl, -(alkyl)p"heterocycle", -(alkyl)p-CO2"heterocycle" or -(alkyl-CO2)s-(alkyl)t-COR5and , in these formulas, R, s and t independently of each other 0 or 1, "heterocycle" represents a 5 the n heteroatom, represents a nitrogen, oxygen or sulfur, and which may substituted once or more than once, by substituents selected from the group consisting of halogen, alkyl and oxo, R5represents a hydroxy, alkoxy, hydroxy-C1-8-alkoxy, C1-8-alkoxyalkane, Tiltonsville, aryl, or aralkyl, or a group of the formula-NR6R7or-O-alkyl-NR6R7and , in these formulas, R6and R7independently of one another represent hydrogen or alkyl, and R14and R15independently of one another represent hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, carboxyl or acyl; or where R' is a group of formula -(ALK)q-R1where (ALK) represents alkyl, alkenyl or quinil, q is 0 or 1, R1represents fornillo group; and Rrepresents -(alkyl)m-CO2R8where m is 0 or 1, R8represents a group of formula -(alkyl)p-NR9R10where R is 0 or 1, and R9and R10together with the nitrogen atom to which they are attached, form a piperazinilnom group, possibly substituted by acyl
FIELD: medicine, pharmacy, pharmaceutical industry.
SUBSTANCE: invention relates to tablets covered by envelope for masking taste of active substance. The core pharmaceutical composition comprises ciprofloxacin as an active component and the following accessory substances - microcrystalline cellulose, crosspovidon, magnesium stearate, lactose, talc, and maize starch. The core envelope comprises hydroxypropylmethylcellulose, titanium dioxide, collidone, propylene glycol, polyethylene oxide and talc. Also, invention describes a method for preparing the sold dosed formulation. Invention provides satisfactory technological properties of tableted mass, preparing plastic, luster core envelope not delaying the release of ciprofloxacin.
EFFECT: improved and valuable properties of composition, improved method for preparing formulation.
3 cl, 5 ex