Pharmaceutical tablet

FIELD: medicine, pharmacy.

SUBSTANCE: invention represents a pharmaceutical tablet comprising a core and bound envelope wherein (a) core comprises solid particles of water-soluble dye dispersed in matrix, and (b) envelope comprises hellanic gum. Due to the presence of water-soluble dye in the tablet core it shows spotted shape that provides easy recognition of the tablet. The tablet is useful for peroral and intraoral administration.

EFFECT: improved and valuable properties of tablet.

30 cl, 6 ex

 

The technical FIELD TO WHICH the INVENTION RELATES.

The present invention relates to oral input pharmaceutical forms, more specifically to the pills.

The LEVEL of TECHNOLOGY

Tablets are the most common and convenient pharmaceutical form for oral administration of drugs. An important functional attribute of the tablet is that it is easily identified by appearance, including size, shape, surface texture, markings and color. This easy readability is important to minimize errors in the hand and allows patients receiving multiple drug therapy, to distinguish between drugs taken at different times or with different periodicity. Many drugs currently formulated in the form of tablets, many of these drugs are formulated for different strength of the dosage, and therefore it is becoming more important, but harder to ensure that any new tablet has a unique appearance.

In particular, the range legkorastvorimyh colors available to the developer tablets is limited. To some extent this problem is alleviated by the use of multi-colored, two-tone or multi-colored pills. However, there remains a need in the technology for tablets, with the University of the unique color images of the surface.

In the case of coated tablets, color can be an attribute of the surface of the shell. For example, the number of opaque pigments can be added to formulations for shells tablets, such as formulations based on ethylcellulose; these pigments pure white or colored view of the coated tablet. Alternatively, the membrane surface can be bright and transparent, and the color-coated tablets controlled color core tablet lying under the shell.

In U.S. Patent No. 6326028, Nivagiolli et al., included in this description by reference, describes shell tablet containing Gellan gum. It is said that this shell is convenient for tablets, taken orally, and gives a good appearance, identifitsiruemosti, taste sensations, reduced the degree of dustiness, stability, color, and/or progladyvaet.

In International patent publication no WO 01/10406 included in the present description by reference, describes compositions that are suitable for a wide range of ways of introducing sildenafil citrate, including buccal and sublingual route. Described preferred compositions comprise a solution, gel, semi-solid substance, suspension, melirovanie dosing device, transdermal patch, or film. States that such compounds may include heliopause the system, for example, 0.5 to 10% Gellan gum.

In International patent publication no WO 02/05820 included in the present description by reference, discloses a film dosage forms containing sildenafil citrate. These dosage forms are prepared by mixing the solid dispersion of sildenafil citrate and water-soluble sugar hydrocolloid and optionally other ingredients; when placed on a mucous surface, they form the shell, which subsequently decomposes and dissolves to release sildenafil. Gel sodium salt is listed among the hydrocolloids that can be used in such film dosage forms.

In U.S. Patent No. 6291506, Levin, included in the present description by reference, describes what ophthalmic drug carvedilol may be formulated for ocular injection due to his suspension agent, such as Gellan gum, which will increase the time of contact of the cornea with the drug. In the specified publication considered other possible dosing methods for the preparation. The claimed method by which the drug is dosed through a selection of ways receipts, including sublingual.

The INVENTION

In this application the proposed pharmaceutical tablet consisting of a core and its associated shell, in which (a) ser is Zevina contains particles of solid water-soluble dye, dispersed in the matrix, and (b) the coating contains Gellan gum.

This tablet is specially suitable for oral or interferonalpha introduction, for example for delivery of the drug contained in the core tablet, the patient, such as man. The term "oral" here refers to the introduction through the mouth, drawing it swallowed the pill without prior substantive decomposition tablets in the mouth, so that absorption of the drug typically occurs in the gastrointestinal tract. The term "intra-oral" here refers to the introduction by placing the tablet in the mouth of a patient, where the tablet is decomposed and/or dissolved, so that the absorption of the drug typically occurs at least partially through the mucosa of the oral cavity. For interferonalpha the introduction of the tablet can be placed in or on any part of the oral cavity, but the premise tablets sublingual or buccal space is preferable.

Tablet alternative may be dissolved or dispersed in the liquid base, preferably in water, and swallowed as one admission.

Tablets according to the invention possess an unusual mottled appearance. Without going into theory, it is believed that during the process of coating the core of the aqueous shell composition containing Gellan gum, dye particles in contact is e composition of the shell is partially decomposed, inducing color "bleed" into the shell in the area of each particle. Then the color becomes fixed when the drying of the membrane. Spotted the figure is highlighted and reproduced more attractive or gracefully Zelenoglazoe surface texture, which gives Gellan gum. As described in more detail below, a variety of characteristics of the spotted pattern of the tablets according to the invention are possible and practical, providing new opportunities for a manufacturer seeking to make easy to identify a pill.

As an additional advantage, spotted the figure of the tablets according to the invention can hide a small unpainted areas that can be a result of changes in processing conditions.

Other properties, features and advantages of the present invention will be apparent from the following description.

DETAILED description of the INVENTION

The tablet according to the invention can be a pill placebo, i.e. not containing at its heart drug or other active agent. Preferably the tablet according to the invention contains in the core of therapeutically and/or prophylactically useful amount of a drug, more preferably of drug that is mainly used by oral or interferonalpha introduction.

N the example, the drug present in the core tablet according to the invention, chosen from the following illustrative classes: inhibitors of angiotensin-converting enzyme; α-adrenergic agonists; β-adrenergic agonists; α-adrenergic blockers; β-adrenergic blockers (beta-blockers); inhibitors of alcohol; inhibitors alsoreported; aldosterone antagonists; amino acids; steroids; analgesics (both narcotic and non-narcotic); anesthetics; anorexic; antacids; antihelminthic drugs; agents against acne; antiallergic drugs; antiandrogens; antianginal agents; sedative agents; antiarrhythmic agent; Antiasthmatic agents; antibacterial agents and antibiotics; drugs against alopecia and baldness, protivooterne means; antibodies; anticholinergic drugs; anticoagulants and blood thinners; antiaritmicheskie drugs; anti-convulsants; antisemitische drugs; antidepressants; antidiabetic agents; Antidiarrheals; antidiuretic; antidotes; anti-emetics; antiestrogens; antiflatulent; antifungal agents; antigens; antiglaucoma agents; antihistamines; antihypertensive means; antihyperlipidemics means; anticipates the main means; antihyperlipidemia agents; antihypotensive means; anticipation tools; anti-infective tools; anti-inflammatory (both steroidal and non-steroidal) funds; antimalarial agents; agents against migraine; antineoplastic; anti-obesity; anti-Parkinson agents and antidyskinetic; antipneumocystis agents; Antiprotozoal agents; antipruritic means; antipsoriatic; antipsychotics; antipyretics; Antirheumatic means; antisecretory agents; antishock drugs; antispasmodic; antithrombotic agents; anticancer agents; antitussives; antiulcer means; antiviral agents; anxiolytics; microbicides; seals bones; bronchodilators; calcium channel blockers; carbonic anhydrase inhibitors; cardiotonic and the pacemakers; chemotherapeutic means; cholagogue; cholinergic means; means for treatment of chronic fatigue syndrome; CNS stimulants; coagulants; contraceptives; means for treatment of cystic fibrosis; anti money; diuretics; agonists of dopamine receptor; receptor antagonists dopamine; enzymes; estrogens; expectorants; means for treatment of gastric hyperactivity; glucocorticoids; hemostatic; inhibitors of the reductase the coenzyme And human menopausal gonadotropin; hormones; hypnotics means; immunomodulatory agents; immunosuppressants; laxatives; means for treating diseases of the oral cavity and periodontal diseases; miotti; monoamine oxidase inhibitors; mucolytics; means for treatment of multiple sclerosis; muscle relaxants; mydriatic; narcotic antagonists; antagonists of the NMDA receptor; oligonucleotides; ophthalmic preparations; rotoscoliosis means; peptides, polypeptides and proteins; polysaccharides; POCs; prostaglandins; protease inhibitors; promoters of breath; sedatives; inhibitors of serotonin uptake; sex hormones, including androgens; drugs used for Smoking cessation; smooth muscle relaxants; stimulants smooth muscles; thrombolytic drugs; tranquilizers; podnikatel urine; drugs for the treatment of urinary incontinence; vasodilators; vasoprotective; and combinations thereof.

It is clear that any reference in the present description on the specific composition of the drug includes the tautomers, the stereoisomers, salts, and prodrugs of the compound and is non-specific for any form of drug in the solid state.

In one embodiment, the drug contained in the core tablet is a drug used to combat Smoking, such as nicotine metabolite of nicotine or not containing nick the Tina tool used in the fight against Smoking, such as bupropion, ibogain.

Illustratively, a drug used for Smoking cessation choose from nicotine and its metabolites (for example, cotinine, narcotine, nornicotine, nicotine-N-oxide, cotinine-N-oxide, 3-hydroxycotinine and 5-hydroxycotinine), Ibogaine, bupropion and its metabolites (e.g., Erythro - and threo-aminoalcohols of bupropion, Erythro-aminodiol bupropion and hydroxybupropion), lobelin, selegiline, risperidone and its 9-hydroxymetabolites, desmethylselegiline, substituted derivatives of pyridine (for example, 1-[(6-chloro-3-pyridinyl)methyl]-2-imidazolidine, 1-[(6-chloro-3-pyridinyl)methyl]-2-imidazothiazole and its analogues), mecamylamine, desipramine, uoxetine, ropinirole, trimetaphan, trimethylamine, doxepin, 2-(3-course)-3,5,5-trimethyl-2-morpholinol, anxiolytics (for example, isovaleramide), γ-vinyl GABA (SHG), epibatidine and its derivatives, compounds 7-azabicyclo-[2,2,1]-heptane and-Heptene, naltrexone, nalmefene, ketamine, hexamethonium, pentalene, dihydro-β-erythroycin, arestin, d-tubocurarine, pempidine, chlorisondamine, amantadine, heterosexualisation, benzyliden and cinnamylpiperazine, derivatives abandonation, N-(pyridinylmethyl)-heterocyclization and antagonists of the receptor NK-1 (for example, 9-bromo-1,2,3,4,5,6-hexahydro-1,5-methane-pyrido[1,2-a][1,5]diasorin-8-he).

In another embodiment is sushestvennee drug contained in the core tablet, is an antibacterial drug. Illustrative of such a drug may be an antibiotic, such as aminoglycoside, amphenicol, ansamycin, carbapenems, cephalosporins, cephamycins, monobactams, oxazepam, penicillin, lincosamides, macrolides, polypeptide or tetracycline; or synthetic antibacterial agent, such as 2,4-diaminopirimidina, nitrofuran, oxazolidinone, hinolan or equivalent, sulfonamide or sulfon. The currently favored antibacterial agents include the following illustrative examples: amikacin, azithromycin, cefixime, cefoperazone, Cefotaxime, ceftazidime, ceftizoxime, Ceftriaxone, chloramphenicol, ciprofloxacin, clindamycin, colistin, demeclocycline, doxycycline, erythromycin, gentamicin, lincomycin, linezolid, mafenide, metatsiklina, minocycline, neomycin, norfloxacin, ofloxacin, oxytetracycline, pirlimycin, polymyxin B, pyrimethamine, silver sulfadiazine, sulfacetamide, sulfisoxazole, tetracycline, tobramycin, trimethoprim and its compounds. In one embodiment, an antimicrobial agent contained in the core tablet is an oxazolidinone, for example selected from (S)-N-[[3-[3-fluoro-4-[4-(hydroxyacetic)-1-piperazinil]phenyl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide (eperezolid), (S)-N-[[3-[3-fluoro-4-[4-(morpholinyl)]phenyl]-oxo-5-oxazolidinyl]methyl]ndimethylacetamide (linezolid), N-[(5S)-3-[3-fluoro-4-[4-(2-toroidal)-3-oxo-1-piperazinil]phenyl-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide, (S)-N-[[3-[5-(3-pyridyl)thiophene-2-yl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide and (S)-N-[[3-[5-(4-pyridyl)pyrid-2-yl]-2-oxo-5-oxazolidinyl]methyl]acetamidomalonate.

In another embodiment, the drug contained in the core of the tablet, as an agent against migraines. Illustrative of such agent is alkylresorcinol, such as caffeine; agonist dopamine D2receptor, for example aspirated or lisuride; the modulator of the GABAAreceptor, for example ganaxolone; agonist of the receptor 5-hydroxytryptamine (5-HT), such as almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan or zolmitriptan; LPV or its derivatives such as ergotamine or digidroergotamin; or vetmousetrap, for example dotarizine, fonadin or lomerizine.

In another embodiment, the drug contained in the core tablet, used for the treatment or prevention of ophthalmic disorders.

Illustrative of such ophthalmic drug can be antibacterial agent, for example selected from the classes listed above.

Alternative or in addition, such an ophthalmic drug may illustratively be a decreasing vnutriplevralnoe or intraocular pressure Agen the Ohm, such as (a) α-adrenergic agonist or sympathomimetic, for example adrenalin, apraclonidine, brimonidine or dipivefrin; (b) β-adrenergic blocker, such as acebutolol, daprela, alprenolol, atenolol, betaxolol, buretrol, bufuralol, bunitrolol, bunolol, bupranolol, carteolol, carvedilol, atemolol, despopoulos, labetalol, levobunolol, metipranolol, metoprolol, nadolol, neftaly, oxiranyl, penbutolol, pindolol, practolol, pronethalol, propranolol, sotalol, timolol, tolamolol, celiprolol or wainola; () carbonic anhydrase inhibitor such as acetazolamide or dorzolamide; or (d) a prostaglandin or its analogue, such as analogs of prostaglandin F2asuch as bimatoprost, latanoprost, travoprost or unprotonated.

Alternative or in addition, such an ophthalmic drug illustrative can be Mitica, such as carbachol, physostigmine or pilocarpine.

Alternative or in addition, such an ophthalmic drug illustrative can be anti-inflammatory agent, such as non-steroidal anti-inflammatory agent, preferably selective MOR-2 inhibitory drug, for example, selected from the medications listed below.

In another embodiment, the drug contained in the core tablet is analge the ICOM, antipyretic or anti-inflammatory agent, such as aceclofenac, acemetacin,e-acetamidomalonate acid, acetaminophen, acetaminoohen, acetanilide, acetylsalicylic acid (aspirin), S-adenosylmethionine, alclofenac, alclometasone, Alfentanil, Alveston, allylprodine, alminoprofen, aloxiprin, Alphaprodine, bis(atsetilsalitsilata) aluminum, amcinonide, amfenac, aminofluorescein, 3-amino-4-hydroxipropionic acid, 2-amino-4-picoline, aminopropyl, aminopyrine, amixetrine, ammonitella, ampiroxicam, amtolmetin, Anileridine, antipyrine, entretenir, Amazon, beclomethasone, bendazac, benorilate, benoxaprofen, benzoperylene, benzydamine, benzylmorphine, bioprotein, betamethasone, Bezitramide, α-bisabolol, bromfenac,p-bromoacetanilide, acetate 5-bromosalicylic acid, bromocriptin, Buletin, Burlakova acid, bukola, budesonide, bufexamac, boydson, buprenorphine, buttetin, butibufen, butorphanol, carbamazepine, carbafen, carprofen, keralam, celecoxib, chlorbutanol, chloroprednisone, chlorination, holinsalitsilat, cinchophen, cinmetacin, ciramadol, clidanac, clobetasol, clocortolone, cloretazine, clonitazene, clonixin, clairac, cloprednol, cloves, codeine, codeinebased, codeinefosfaat, codeinsight, cortisone, cortisol, cropropamide, crocheted, deflazacort, desomorphine, which toned, desoximetasone, dexamethasone, dexoxadrol, dextromoramide, dezocine, diampromide, diclofenac, dipannita, divinename, diflorasone, diflucortolone, diflunisal, difluprednate, Dihydrocodeine, dihydrocodeinone, dihydromorphine, dihydroxyaluminum the atsetilsalitsilata, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl, Dipipanone, deprecates, dipiro, diazol, droxicam, emorfazone, antenova acid, enoxolone, epirizole, eptazocine, Etisalat, ethenzamide, ethoheptazine, Eloxatin, ethylmethylthiambutene, Ethylmorphine, etodolac, etofenamate, etonitazene, etoricoxib, eugenol, felbinac, fenbufen, fenclova acid, fendosal, fenoprofen, fentanyl, fentiazac faradina, feprazone, floctafenine, flashcart, fluchloralin, floranova acid, flumetazon, flunisolide, flunixin, flunoxaprofen, fluorenylacetamide, fluocinonide, fluocortin, fluocortolone, fluoresant, fluorometholone, flaperon, flupirtine, flupredniden, fluprednisolone, fluprofen, flurandrenolide, flurbiprofen, farmacita, posposil, gentisic acid, glutenin, glucometry, glycolicglycolic, guaiazulene, halcinonide, halobetasol, halapeno, hydrocodone, hydrocortamate, hydrocortisone, hydromorphone, hydroxypethidine, ibufenac, ibuprofen, ibuproxam, imidazolidinyl, indomethacin, indoprofen, isophtalic, isolator, and ommadon, sonksen, isoxepac, isoxicam, Ketobemidone, Ketoprofen, Ketorolac,p-lactofree, lefetamine, Levorphanol, lofentanil, lonazolac, lornoxicam, loxoprofen, literacyrelated, mazipredon, meclofenamic acid, Madison, mefenamovaya acid, meperidine, meprednisone, meptazinol, mesalamine, metazocine, methadone, metotrimeprazin, methylprednisolone, medicinova acid, metafolin, metopon, mofebutazone, movetalk, Morison, morphine, morphinehydrochloride1, martinslife, morpholinoethyl, mirfin, nabumeton, nalbuphine, 1 afterselect, naproxen, Narain, nefopam, Nicomorphine, rivenson, niflumova acid, nimesulide, 5'-nitro-2'-propoxyethanol, norlevorphanol Normethadone, normorphine, norpipanone, olsalazine, opium, oxaceprol, oxiplatin, oxaprozin, oxycodone, Oxymorphone, oxyphenbutazone, papaveretum, paramethasone, phrenilin, parecoxib, parceled, pentazocine, personsal, phenacetin, phenadoxone, phenazocine, phenazopyridinee, fenocor, Phenoperidine, fineperson, phenylacetylcarbinol, phenylbutazone, fenilsalitsilat, phenyramidol, Pittodrie, piminodine, pipeuse, piperylene, pirprofen, pyrazole, piritramid, piroxicam, pranoprofen, prednicarbate, prednisolone, prednisone, prednesol, prednisone, proglumetacin, proheptazine, promedol, propacetamol, propiram, propoksifen, propifenazona proquazone proteinemia acid, proxitol, ramification, Remifentanil, remotelycontrolled, rofecoksib, saleclomid, salicin, salicylamide, salicylamide-aboutacetic acid, salicylic acid, slicicama acid, salsalate, silverin, symetric, Sufentanil, sulfasalazin, sulindac, superoxide dismutase, suprofen, skibotn, talniflumate, tenidap, tenoxicam, meropenam, tetrandrine, thiazolinones, tiaprofenic acid, tiaramide, tilidin, tinoridine, tixocortol, telenova acid, tolmetin, tramadol, triamcinolone, tropein, valdecoxib, viminal, xenmotion, xenoprof, zaltoprofen or zomepirac.

In a specific embodiment, such a drug is a selective MOR-2 inhibitory drug, for example a compound of formula (I)

or sister prepreparation, or its pharmaceutically acceptable salt, where:

A denotes a Deputy selected from partially unsaturated or unsaturated heterocycles or partially unsaturated or unsaturated carbocyclic ring, preferably a heterocyclic group selected from pyrazolinones, purananooru, isoxazolidine, peridiniales, cyclopentanediol or pyridazinyl groups;

X denotes O, S or CH2;

n denotes 0 or 1;

R11denotes at least one Deputy, SEL is p from heterocyclyl, cycloalkyl, cycloalkenyl and aryl, possibly substituted in a suitable replacement for the position by one or more radicals selected from alkyl, halogenoalkane, ceanography, carboxyl, alkoxycarbonyl, hydroxyl, hydroxyalkyl, halogenlampe, amino, alkylamino, killingray, nitro, alkoxyalkyl, alkylsulfonyl, halide groups, alkoxygroup and ancilliary;

R12denotes methyl, amino or aminocarbonyl;

R13represents one or more radicals selected from peridogram, halide, alkyl, alkenyl, quinil, carbonyl group, ceanography, carboxyl, cyanoalanine, geterotsiklicheskikh, alkoxygroup, allylthiourea, alkylcarboxylic, cycloalkyl, aryl, halogenoalkane, heterocyclyl, cycloalkenyl, aralkyl, geterotsiklicheskikh, acyl, alkylthiomethyl, hydroxyalkyl, alkoxycarbonyl, arylcarbamoyl, aralkylamines, aralkyl, alkoxyalkyl, alltoall, aryloxyalkyl, kalkiliya, alcoxialchil, alkoxylalkyl, alkoxycarbonylmethyl, aminocarbonyl, aminocarbonylmethyl, alkylaminocarbonyl, N-arylenecarborane, N-alkyl-N-arylenecarborane, alkylaminocarbonyl, carboxyethyl, alkylamino N-killingray, N-aralkylamines, N-alkyl-N-aralkylamines, N-alkyl-N-arylamino the group, aminoalkyl, acylaminoalkyl, N-alluminare, N-aralkylamines, N-alkyl-N-aralkylamines, N-alkyl-N-alluminare, alloctype, urlcategory, aristocraty, arkitip, alkylsulfonyl, alkylsulfonyl, aminosulfonyl, alkylaminocarbonyl, N-arylaminomethylene, arylsulfonyl, N-alkyl-N-arylaminomethylene, and R13can be substituted in a suitable replacement for the position by one or more radicals selected from alkyl, halogenoalkane, ceanography, carboxyl, alkoxycarbonyl, hydroxyl, hydroxyalkyl, halogenlampe, amino, alkylamino, killingray, nitro, alkoxyalkyl, alkylsulfonyl, halide groups, alkoxygroup and ancilliary; and

R14choose from peridogram and halide groups.

In preferred compositions in accordance with this embodiment of the election SOH-2 inhibitory drug is a compound described by formula (II)

where R15denotes methyl, amino or aminogroup, R16denotes hydrogen or C1-4-alkyl or-alkoxygroup, X=N or CR17where R17denotes hydrogen or halogen, Y and Z independently represent the carbon atoms or nitrogen defining adjacent atoms of a five - and six-membered ring, the cat is which is unsubstituted or substituted in one or more of the provisions oxo-, halide, methyl or halogenosilanes groups. Preferably such five - and six-membered ring are Cyclopentanone, Furmanova, methylpyrazolo, isoxazolyl and pyridine cycles, substituted not more than one position.

In another preferred compositions in accordance with this embodiment of the election SOH-2 inhibitory drug is a compound described by formula (III)

or related preprepared, or its pharmaceutically acceptable salt, where X=O, S, or N-lower alkyl; R18indicates the lowest halogenated; R19denotes hydrogen or halogen; R20denotes hydrogen, halogen, lower alkyl, lower alkoxy or halogenlampe, lower alkylsulphonyl, lower dialkylaminoalkyl, lower alkylaminocarbonyl, lower aralkylamines, lower heteroarylboronic, or 5 - or 6-membered nitrogen-containing heterozygosity; and R21and R22independently represent hydrogen, halogen, lower alkyl, lower alkoxygroup or aryl.

A particularly suitable compound of formula (III) is a (S)-6,8-dichloro-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid.

In another preferred compositions in accordance with this embodiment of izbirat the local SOH-2 inhibitory drug is a 5-alkyl-2-arylaminovinylketones acid or its derivatives. Particularly useful compounds of this class are 5-methyl-2-(2'-chloro-6'-foronline)phenylacetic acid and its pharmaceutically acceptable salts.

Illustrative, celecoxib, deracoxib, valdecoxib, parecoxib, rofecoksib, etoricoxib, 2-(3,5-differenl)-3-[4-(methylsulphonyl)phenyl]-2-cyclopenten-1 -, (S)-6,8-dichloro-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid, 2-(3,4-differenl)-4-(3-hydroxy-3-methyl-1-butoxy)-5-[4-(methylsulphonyl)phenyl]-3-(2H)-pyridazinone and its salts applicable in the compositions according to the invention.

In another embodiment, the drug contained in the core tablet is used for the treatment and/or prevention of sexual dysfunction in men and/or women. This drug may illustratively be (a) an inhibitor of phosphodiesterase type 5 (PDE5), for example sildenafil, tadalafil or vardenafil, and (b) inhibitor cyclogyl phosphodiesterase, (b) an activator zaklamp, (g) α-adrenergic antagonist, such as phentolamine or yohimbin, or (d) dopaminergic agonist, such as apomorphine. Such a drug may be a compound of the formula (V)below. An alternative drug contained in the core tablet may be other than a drug for the treatment and/or prevention of sexual dysfunction. As another alternative, the drug contained in the core tablet may amend the change for the treatment and/or prevention of sexual dysfunction, but different from the compounds of formula (V)below.

Illustrative compositions of the drug used, for example, for the treatment of Parkinson's disease or sexual dysfunction, is contained in the core tablet, is a compound of formula (V)

or its pharmaceutically acceptable salt, where

R1, R2and R3identical or different, denote H, C1-6-alkyl (possibly phenylselenenyl)3-5alkenyl or quinil or C3-10-cycloalkyl, or where R3as mentioned above, and R1and R2cyklinowanie associated with the N atom, in the form pyrrolidinyloxy, piperidinyloxy, morpholinium, 4-methylpiperazine or imidazolinones groups;

X denotes H, F, Cl, Br, I, OH, C1-6-alkyl or

-alkoxygroup, CN, carboxamide, carboxyl or (C1-6alkyl)carbonyl;

And denotes CH, CH2, CHF, CHCl, CHBr, CHI, CHCH3, C=O, C=S, CSCH3, C=NH, CNH2, CNHCH3, CNHCOOCH3, CNHCN, SO2or N;

In denotes CH, CH2, CHF, CHCl, CHBr, CHI, C=O, N, NH or NCH3and n denotes 0 or 1; and

D represents CH, CH2, CHF, CHCl, CHBr, CHI, C=O, N, NH or NCH3.

Preferably the compound of formula (V) or its water soluble salt.

Pharmaceutically acceptable salts of the compounds of formula (V) include, but are not limited to, salts of the following acids: chlorowodor the one, Hydrobromic, sulfuric, methanesulfonic, phosphoric, nitric, benzoic, citric, tartaric, fumaric and maleic acids, and mono - and dicarboxylic acids of the formula CH3-(CH2)n-COOH, noos-(CH2)n-COOH where n is 0 to 4, for example malonic acid.

Particularly preferred salts are the hydrochloride and maleate, ie (Z)-2-butenedioate.

The compounds of formula (V) and their salts can be prepared by known per se methods, including the method described in patent literature cited in this application. However, the present invention is not limited by the method used for the preparation of therapeutic agent.

Preferred compounds of formula (V) are disclosed in General or, in particular, in U.S. patent No. 5273975, Moon et al. Especially preferred are the compounds of formula (VI)

where X denotes O or S, and pharmaceutically acceptable salts.

Core tablets, applicable in accordance with the invention, can be prepared by any suitable method known from the prior art. The core in accordance with the invention includes a matrix in which are dispersed solid particles of water-soluble dye. Any suitable filler or fillers can form a matrix. For PE the oral tablets matrix typically contains a diluent or carrier, for example, lactose and/or starch, and can moreover contain additional excipients such as binding agents, disintegrant, wetting agents, etc. For interpersonally tablets matrix typically contains water-soluble sugar, such as mannitol and/or maltose. If the drug contained in the core, the drug is also dispersed in the matrix.

The final appearance of the tablet depends in part upon the selection of a water-soluble dye and the number and size of solid particles of the dye. For example, relatively large particles will tend to the formation of a spotted pattern with large color blocks than would be formed by smaller particles; and a relatively larger number of particles will tend to form a spotted pattern in which color covers most of the surface tablet, than would be formed by a smaller number of particles. More water-soluble dye tends to form large and/or less separate color blocks than would be formed less water-soluble dye.

If desired, the solid particles of more than one water-soluble dye may be contained in the core, facilitating two-tone or multi-colored appearance of the tablets.

Core covered by a shell composition containing Gellan gum, as described in more detail below, the Shell is typically present in an amount, representing a weight gain from about 0.1% to about 5%, but if desired can be used in larger or smaller amounts. Preferably Gellan gum is from about 25% to about 100%, more preferably from about 50% to about 100% by weight of the shell.

Preferably the shell is filling the shell. In the present description by "filling the shell understands shell composed at least at the time of deposition of the shell on the core only of filling materials, i.e. mostly not contain drug. It is clear that in the manufacturing process and storage can potentially happen migration of the drug substance from the core to the shell of the tablet according to the invention, but they are mostly minimal. Thus, the drug substance, if present in the tablet, for the most part enclosed in the core, where it is not mixed with Gellan gum.

Any Gellan gum can be used in the composition of the shell, but it is preferable to use decellerating Gellan gum, such as manufactured under the trademark KelcogelTM. Optionally, one or more gums and/or biopolymers, such as alginates may be present in the composition of the shell.

The composition of the shell contains raspily carrier, preferably water, with rest is adopted or dispersed in it Gellan gum and optionally one or more additional fillers. Preferably the composition of the shell consists of solid materials in a total concentration from about 1% to about 10% by weight and Gellan gum at a concentration of from about 1% to about 5% by weight.

Additional fillers contained in the shell can contain one or more buffer agents, typically in a concentration of from about 0.03% to about 3% by weight; one or more plasticizers, typically in a concentration of from about 0.03% to about 3% by weight; and/or one or more dispersing and/or emulsifying agents, typically in a concentration of from about 0.03% to about 3% by weight. An example of a suitable buffering agent is sodium citrate. An example of a suitable plasticizer is propylene glycol. An example of a suitable dispersing or emulsifying agent is lecithin. Flavouring agents may also be included in the composition of the shell, if desired.

The composition of the membrane can be prepared by any method, including the dissolution of Gellan gum and other optional fillers in the carrier, preferably water. How to add non-critical. The water is preferably heated, for example, to a temperature of from about 55°C to 85°C. Gellan gum and other fillers, if present, are added during the mixing up until all the ingredients are not homogeneous dispersion is iroute. Get shell liquid is preferably supported at an elevated temperature during the mixing and subsequent procedures spraying.

Subject to the coated surface of the core tablets are placed in a suitable device for coating, for example in the tank to cover, and preferably pre-heated to a substrate temperature from about 50°C to 70°C. Shell liquid is sprayed on the tablets under conditions which will be easily optimized by the person skilled in the art. Plating continues until, until you applied the number of shell solution, equivalent to a weight gain from about 0.1% to about 5%. The obtained coated tablets preferably cooled to ambient temperature, or from about 20°With up to about 35°to discharge from the tank for cover.

Conditions of coating and cooling can also affect the clarity of the color picture of the finished tablets. For example, if the coating is carried out at low temperatures and/or if the cooling is slow, so that solid particles of the dye in the core was exposed to water for a longer period of time, typically turns a mottled pattern with large color blocks.

The core of the illustrative sublingual tablets in of the bretania, containing as active agent salt, for example, maleate, sumanirole or (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinoline-2(1H)-tion, has the following composition:

active agent)0.1 to 3% equivalent
free base
mannitol50-90%
powder sorbitol10-40%
hydroxypropylcellulose0-10%
xanthan gum0-5%
flavouring agent0-0,5%
water-soluble dye0-0,5%
colloidal silicondioxide0-1%
magnesium stearate0.5 to 5%

All percentages are given by weight.

The core of another illustrative tablets according to the invention containing as active agent salt, for example, maleate, sumanirole or (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinoline-2(1H)-tion, has the following composition:

the active agent0.1 to 3% equivalent
free base
the lactose monohydrate50-85%
has preliminarily gelatinizing starch 10-45%
xanthan gum0-5%
flavouring agent0-0,5%
water-soluble dye0-0,5%
colloidal silicondioxide0-1%
magnesium stearate0.5 to 5%

All percentages are given by weight.

The core of another illustrative sublingual tablets according to the invention containing as active agent salt, for example, maleate, sumanirole or (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinoline-2(1H)-tion, has the following composition:

the active agent0.1-0.3% of the equivalent
free base
microcrystalline cellulose30-70%
pre gelatinizing starch25-65%
croscarmellose sodium0-10%
xanthan gum0-5%
flavouring agent0-0,5%
water-soluble dye0-0,5
colloidal silicondioxide0-1%
magnesium stearate0.5 to 5%

All of the percentage p is Evegeny mass.

EXAMPLES

The following examples illustrate aspects of the present invention, but they should not be construed as limitations. In these examples, "compound Z" refers to(R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinoline-2(1H)-tion, maleate salt. All percentages are given by weight, unless otherwise indicated.

Example 1

Was prepared composition sublingual tablets with the following composition:

connection Z1,11%
AvicelTMPH 101 (microcrystalline cellulose)46,71%
starch 1500 use (pre -
gelatinizing starch)44,00%
croscarmellose sodium NFto 5.00%
colloidal silicondioxide NF0,50%
cinnamon flavoring0,14%
mint flavor0,04%
dye (cherry shade #1362, Crompton&Knowles)0,50%
magnesium stearate2,00%

Pre gelatinizing starch and dye were mixed in linoleate mixer for 2 minutes or until homogeneous mixing. Then the following ingredients separately was layered on the mixture:connection Z; microcrystalline cellulose; colloidal silicondioxide; croscarmellose sodium. Mixing in linoleate stirrer was renewed for an additional 2 minutes. If the dye has not been adequately dispersed in the resulting mixture, stirring was continued with 1-minute increment, haven't seen a good dispersion of the dye. Selected a small portion of the mixture and manually mixed with magnesium stearate to form premix stearate. Premix, together with flavors, added in donolato stirrer and were stirred for 1 minute for the formation of oil-billet tablets.

Oiled workpiece tablets were unloaded from linoleate stirrer and kept dehydrated in hermetically sealed containers until you are ready to pelletizing. Tablets manufactured by passerovaniya using 12/32 inch (approximately 9 mm) Plain/Plain nozzles of the lesser curvature to the following specifications:

weight pills180 mg
stiffness3-4 SCU
brittle<0,5%

Example 2

Sublingual tablets prepared as in Example 1, coated shell, containing Gellan gum in accordance with the following procedure.

p> Prepared shell liquid of the following composition:

Gellan gum (KelcogelTM)2,00%
sodium citrate0,13%
propylene glycol0,40%
lecithin0,20%
deionized water97,27%

Deionized water was heated to 70°C. the Other ingredients were added with stirring until then, until the ingredients were not homogeneous dispersed. The obtained shell liquid with a solids content 2,73% maintained at a temperature of 70°during the mixing and subsequent procedures spraying.

Tablets of Example 1 in the amount of 700 g was placed in a 12-inch (300 mm) tank coating and pre-heated to a temperature of the substrate 60°C. Shell liquid deposited on the tablets in the following conditions:

the air temperature at the output50-60°
speed tank16 rpm
air flow30-35 Kubratovo/min
(0,84-0,98 m3/min)
pressure spraying air10 psi (69 kPa)
setting peristaltic pump15-20 g/min

Spraying was continued until until paid a number of shell solution, equivalent to 1.2% of the weight gain. The obtained coated tablets was cooled to 30°before discharge from the tank for cover.

The tablets had an attractive sildopanai appearance with cherry-red spots.

Example 3

Prepared composition sublingual tablets with the following composition:

connection Z1,05%
mannitol granules70,00%
sorbitol16,57%
hydroxypropylcellulose, type LH-117,00%
xanthan gum2,50%
colloidal silicondioxide NF0,50%
cinnamon flavoring0,14%
mint flavor0,04%
dye (cherry shade #1362, Crompton&Knowles)0,20%
magnesium stearate2,00%

The mannitol and the dye was mixed in linoleate mixer for 2 minutes or until a homogenous mixture. The following ingredients separately was layered on the mixture in Vysokovo astoi mixer: connection Z; sorbitol; hydroxypropylcellulose; xanthan gum; colloidal silicondioxide. Mixing in vysokololtnoe stirrer was renewed for an additional 2 minutes. If the dye has not been adequately dispersed in the resulting mixture, stirring was continued with 1-minute increment, haven't seen a good dispersion of the dye. Selected a small portion of the mixture and manually mixed with magnesium stearate to form premix stearate. Premix together with flavorings added in donolato stirrer and were stirred for 1 minute for the formation of oil-billet tablets.

Oiled workpiece tablets were unloaded from linoleate stirrer and kept dehydrated in hermetically sealed containers until you are ready to pelletizing. Tablets manufactured by passerovaniya using 12/32 inch (approximately 9 mm) Plain/Plain nozzles of the lesser curvature to the following specifications:

weight pills190 mg
stiffness3-4 SCU
brittle<0,5%

Example 4

Sublingual tablets prepared as in Example 3 was coated by a shell containing Gellan gum in accordance with the following procedure.

Prepara is whether shell liquid with the following composition:

Gellan gum (KelcogelTM)2,00%
sodium citrate0,13%
propylene glycol0,40%
lecithin (LipoidTMLS-100)0,20%
flavor0,3%
deionized water96,97%

Deionized water was heated to 70°C. the Other ingredients were added with stirring until then, until the ingredients were not homogeneous dispersed. The obtained shell liquid with a solids content 3,03% maintained at a temperature of 70°during the mixing and subsequent procedures spraying.

Tablets of Example 1 in the amount of 700 g was placed in a 12-inch (300 mm) tank coating and pre-heated to a temperature of the substrate 60°C. Shell liquid deposited on the tablets in the following conditions:

the air temperature at the output50-60°
speed tank16 rpm
air flow30-35 Kubratovo/min
(0,84-0,98 m3/min)
pressure spraying air10 psi (9 kPa)
setting peristaltic pump15-20 g/min

Spraying was continued until until paid a number of shell solution, equivalent to 1.36% of the weight gain. The obtained coated tablets was cooled to 30°before discharge from the tank for cover.

The tablets had an attractive sildopanai appearance with cherry-red spots.

Example 5

Was prepared composition sublingual tablets with the following composition:

connection Z0,43%
AvicelTMPH 101 (microcrystalline cellulose)47,39%
starch 1500 use (pre -
gelatinizing starch)44,00%
croscarmellose sodium NFto 5.00%
colloidal silicondioxide NF0,50%
cinnamon flavoring0,14%
mint flavor0,04%
dye (cherry shade #1362, Crompton&Knowles)0,50%
magnesium stearate2,00%

Pre gelatinizing starch and dye were mixed in linoleate mixer for 2 minutes or until homog is spent mixing. Then the following ingredients separately was layered on the mixture: connection Z; microcrystalline cellulose; colloidal silicondioxide; croscarmellose sodium. Mixing in linoleate stirrer was renewed for an additional 2 minutes. If the dye has not been adequately dispersed in the resulting mixture, stirring was continued with 1-minute increment, haven't seen a good dispersion of the dye. Selected a small portion of the mixture and manually mixed with magnesium stearate to form premix stearate. This premix together with flavors manually sifted through pharmaceutical sieve #20 mesh, then added in donolato stirrer and prevented over 1 minute for the formation of oil-billet tablets.

Oiled workpiece tablets were unloaded from linoleate stirrer and kept dehydrated in hermetically sealed containers until you are ready to pelletizing. Tablets manufactured by passerovaniya using 12/32 inch (approximately 9 mm) Plain/Plain nozzles of the lesser curvature to the following specifications:

weight pills180 mg
stiffness3,5-4 SCU
brittle<0,8%

Example 6

Sublingual the e pills, prepared as in Example 5 coated shell containing Gellan gum in accordance with the following procedure.

Prepared shell liquid with the following composition:

Gellan gum (KelcogelTM)2,00%
sodium citrate0,13%
propylene glycol0,40%
lecithin (LipoidTMLS-100)0,20%
flavor0,3%
deionized water96,97%

Deionized water was heated to 70°C. the Other ingredients were added with stirring until then, until the ingredients were not homogeneous dispersed. The obtained shell liquid with a solids content 3,03% maintained at a temperature of 70°during the mixing and subsequent procedures spraying.

Tablets of Example 5 in the amount of 7000 g was placed in a 34-inch (about 600 mm) tank coating and pre-heated to a temperature of the substrate 60°C. Shell liquid deposited on the tablets in the following conditions:

the air temperature at the output48-55°
speed tank10-14 rpm, pre is respectfully 14
air flow300-400 Kubratovo/min
(an 8.5-11.3 m3/min)
pressure spraying air20-35 psi
(138-242 kPa), preferably about 20 psi
setting peristaltic pump15-40 g/min/nozzle
(spray two sprays),
preferably 30-40 g/min/u.
the temperature of the substrate pills37-50°C, preferably
about 40°

Spraying was continued until until paid a number of shell solution, equivalent to 2,04% weight gain. The obtained coated tablets was cooled to 30°before discharge from the tank for cover.

The tablets had an attractive sildopanai appearance with cherry-red spots.

1. Pharmaceutical tablet comprising a core and its associated shell in which (a) the core contains solid particles of water-soluble dye dispersed in the matrix, and (b) the coating contains Gellan gum.

2. The tablet according to claim 1, having spotted surface.

3. Tablet P1, in which the core contains the drug in a therapeutically and/or prophylactically effective amount.

4. The tablet according to claim 3, in which the drug is chosen from the group consisting of inhibitors of angiotensin-converting enzyme; α-adrenergic agonists; β-adrenergic agonists; α-adrenergic blockers; β-adrenergic blockers (beta blockers); inhibitors of alcohol; inhibitors alsoreported; aldosterone antagonists; amino acids, anabolics, analgesics (both narcotic and non-narcotic); anesthetics; anorexics; antacids; anthelminthic drugs; agents against acne; antiallergic drugs; anti-androgens; antianginal agents; sedative agents; antiaritmikov; anti-asthmatic agents; antibacterial agents and antibiotics; drugs against alopecia and baldness, protivozobnyj means; antibodies; anticholinergic drugs, anticoagulants and blood thinners; antiaritmichesky drugs; anticonvulsants; antiishemiceski drugs; antidepressants; antidiabetic agents; antidiarrheal means; antidiuretics; antidotes; antiemetics; antiestrogens; antiflatulents; antifungal agents; antigens; antiglaucoma agents; antihistamine drugs; and typerating means; antihyperlipidemics means; antihypertensive agents; antihyperuricemic agents; antihypotensive means; antiseptirovannyh funds; anti-infective funds; anti-inflammatory (both steroidal and non-steroidal) funds; antimalarial agents; agents against migraine; antineoplastics; anti-obesity; anti-Parkinson agents and antidyskinetics; antipneumococcic agents; Antiprotozoal agents; antipruritic agents; antipsoriatic; antipsychotics; antipyretics; Antirheumatic means; antisecretory agents; antishock drugs; antispasmodics; antithrombotic means; anticancer agents; antitussives means; antiulcer means; antiviral agents; anxiolytics; microbicides; seals bones; bronchodilators; blockers calcium channels; carbonic anhydrase inhibitors; cardiotonics and pacemakers; chemotherapeutic means; cholagogue; cholinergic means; means for the treatment of chronic fatigue syndrome; CNS stimulants; coagulants; contraceptives; agents for the treatment of cystic fibrosis; decongestants means; diuretics; agonists of dopamine receptor; receptor antagonists dopamine; enzymes; estrogen; face means; means for Leche is of gastric hyperactivity; glucocorticoids; hemostatics; inhibitors of coenzyme a reductase And human menopausal gonadotropin; hormones; hypnotics; immunomodulators, immunosuppressants; laxatives; agents for treating diseases of the oral cavity and periodontal diseases; miotikov; monoamine oxidase inhibitors; mucolytic means; means for the treatment of multiple sclerosis; muscle relaxants; Mydriatics; narcotic antagonists; antagonists of the NMDA receptor; oligonucleotides; ophthalmic preparations; rodoslovnaya means; peptides, polypeptides and proteins; polysaccharides; POCs; prostaglandins; protease inhibitors; promoters of breath; sedatives; inhibitors of serotonin uptake; sex hormones, including androgens, drugs, used for tobacco control; smooth muscle relaxants; stimulators of smooth muscles; thrombolytics; tranquilizers; pagkikita urine; medicines for the treatment of urinary incontinence; vasodilators; vasoprotective; and combinations thereof.

5. The tablet according to claim 3, in which a drug is a drug used for Smoking cessation.

6. The tablet according to claim 5, in which a drug used for Smoking cessation, which are selected from bupropion, Ibogaine, nicotine and its metabolites.

7. The tablet according to claim 3, in which preparatives antibacterial drug.

8. The tablet according to claim 7, in which the antimicrobial agent is an oxazolidinone.

9. The tablet of claim 8, in which the oxazolidinone selected from eperezolid, linezolid, N-[(5S)-3-[3-fluoro-4-[4-(2-foradil)-3-oxo-1-piperazinil]phenyl-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide, (S)-N-[[3-[5-(3-pyridyl)thiophene-2-yl]-2-oxo-5-oxazolidinyl]methyl]ndimethylacetamide and (S)-N-[[3-[5-(4-pyridyl)pyrid-2-yl]-2-oxo-5-oxazolidinyl]methyl]acetamidomalonate.

10. The tablet according to claim 3, in which the drug is an agent against migraines.

11. Tablet of claim 10, in which the agent against migraine is an agonist of 5-HT-receptor.

12. The tablet according to claim 11, in which the agonist 5-HT-receptor selected from the group consisting of almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan or zolmitriptan.

13. The tablet according to claim 3, in which the drug is used for treatment or prevention of ophthalmic disorders.

14. Tablet in item 13, in which the drug is decreasing vnutriplevralnoe or intraocular pressure agent.

15. Tablet 14 in which the step-down vnutriplevralnoe or intraocular pressure agent selected from the group consisting of adrenaline, apraclonidine, brimonidine, dipivefrine, acebutolol, adapalene, alprenolol, atenolol, betaxolol, buretrol, bufuralol, bunitrolol, bunolol, bupranolol, Carter the La, carvedilola, atemolol, despopoulos, labetalola, levobunolol, metipranolol, metoprolol, nadolol, nihinlola, oxiranyl, penbutolol, pindolol, practolol, pronethalol, propranolol, sotalol, timolol, tolamolol, celiprolol, vannella, acetazolamide, dorzolamida, bimatoprost, latanoprosta, travoprost, unoprostone and their combinations.

16. The tablet according to claim 3, in which the drug is an analgesic, antipyretic or anti-inflammatory agent.

17. The tablet according to clause 16, in which the analgesic, antipyretic or anti-inflammatory agent selected from the group consisting of aceclofenac, acemetacin, e-acetamidocinnamic acid, acetaminophen, acetaminophe, acetanilide, acetylsalicylic acid, S-adenosylmethionine, alclofenac, alklometazon, Alfentanil, algestone, allylprodine, alminoprofen, aloxiprin, Alphaprodine, bis(atsetilsalitsilata) aluminum, amcinonide, amfenac, aminofluorescein, 3-amino-4-hydroxybutiric acid, 2-amino-4-picoline, aminopropylene, aminopyrine, amixetrine, ammonitella, ampiroxicam, ntamatungiro, Anileridine, antipyrine, entretenida, Upasana, beclomethasone, bendazac, benorilate, benoxaprofen, benzoperylene, benzydamine, benzylmorphine, bioprofile, betamethasone, Bezitramide, α-bisabolol, bromfenac, p-b is homoacetogenic, acetate 5-bromosalicylic acid, bromocriptine, bucatini, buglakovoj acid, bucolome, budezonida, bufexamac, bumadizone, buprenorphine, butacaine, butibufen, butorphanol, carbamazepine, corbetena, carprofen, karsilama, celecoxib, chlorbutanol, chloroprednisone, chlorination, holinsalicilata, cinchophen, cinmetacin, ciramadol, clidanac, clobetasol, clocortolone, cloretazine, clonitazene, clonixin, kopirati, cloprednol, cloves, codeine, codeinebased, codeinefosfaat, codeinsurance, cortisone, coltivate, cropropamide, crocheted, deflazacort, desomorphine, desonide, desoximetasone, dexamethasone, dexoxadrol, dextromoramide, dezocine, diampromide, diclofenac, defenitly, differered, diflorasone, diflucortolone, diflunisal, difluprednate, Dihydrocodeine, dihydrocodeinone, dihydromorphine, dihydroxyaluminum atsetilsalitsilata, dimenoxadol, dimepheptanol, dimethylthiambutene, dioksifenilalanina, Dipipanone, dipietro, dipirona, dicosola, droxicam, emorfazone, ingenmoney acid, enoxolone, epirizole, eptazocine, Etisalat, ethenzamide, ethoheptazine, etoxazole, ethylmethylthiambutene, Ethylmorphine, etodolac, etofenamate, etonitazene, etoricoxib, eugenol, felbinac, fenbufen, fenclova acid, fendosal, fenoprofen, vent the Nile, fentiazac, farinola, feprazone, floctafenine, flashcart, glucoronide, flufenamic acid, flumetazon, flunisolide, flunixin, flunoxaprofen, fluorenylacetamide, fluocinonide, fluocortolone, fluocortolone, fluorenone, fluorometholone, flaperon, flupirtine, fluprednidene, fluprednisolone, flurocarbon, flurandrenolide, flurbiprofen, formotorola, postsale, hentaimovi acid, glafenine, glucometry, glycylcycline, guaiazulene, halcinonide, halometasone, allopregnane, hydrocodone, hydrocortamate, hydrocortisone, hydromorphone, hydroxypethidine, ibufenac, ibuprofen, ibuproxam, imidazolidinyl, indometacin, indoprofen, softalk, solarola, isomethadone, isolaccia, isoxepac, isoxicam, Ketobemidone, Ketoprofen, Ketorolac, p-lactatemia, lefetamine, Levorphanol, lofentanil, lonazolac, lornoksikama, loxoprofen, literaturinstitut, mazibrada, meclofenamic acid, medrysone, mefenamovoy acid, meperidine, meprednisone, meptazinol, mesalamine, metazocine, methadone, methotrimeprazine, methylprednisolone, medicinova acid, metafolin, metopon, mofebutazone, maffesoli, morazone, morphine, martingaled, martinslife, morpholinacetate, myrophine, nabumetone, nalbufina, 1 naphthylisocyanate, naproxen, narceine, the nave is pam, Nicomorphine, naftazone, niflumova acid, nimesulide, 5'-nitro-2'-propoxyethanol, norlevorphanol, Normethadone, normorphine, norpipanone, olsalazine, opium, oxaceprol, exametazime, oxaprozin, oxycodone, Oxymorphone, oxyphenbutazone, papaveretum, paramethasone, phrenilin, parecoxib, pharsalia, pentazocine, peridocally, fenatsetina, phenadoxone, phenazocine, phenazopyridinee, finokalia, Phenoperidine, Phenoperidine, phenylacetylglutamine, phenylbutazone, fenilsalitsilata, phenyramidol, pictorion, piminodine, piperazine, piperidine, pirprofen, pyrazole, Piritramide, piroxicam, pranoprofen, prednicarbate, prednisolone, prednisone, prednisolo, prednisolone, proglumetacin, proheptazine, promedol, propacetamol, propiram, propoxyphene, propifenazona, proquazone, proteinwas acid, proxitol, nomifensine, Remifentanil, romanoliterotica, rofecoxib, salicylamide, salicin, salicylamide, salicylamide-o-acetic acid, salicylic acid, salicylates acid, salsalate, silverina, simetria, Sufentanil, sulfasalazin, sulindaka, sod, suprofen, skibotn, talniflumate, tenidap, tenoxicam, terfenadine, tetrandrine, thiazolidinedione, tiaprofenic acid, tiaramide, Tilidine, tinoridine, tixocortol, tolfenamic KIS is the notes, tolmetin, tramadol, triamcinolone, trapezina, valdecoxib, Viminale, xenazine, xenoprofile, zaltoprofen and zomepirac.

18. The tablet according to clause 16, in which the analgesic, antipyretic or anti-inflammatory agent are selective MOR-2 inhibitory drug.

19. Tablet p in which the election SOH-2 inhibitory drug is a compound having the formula

where R15denotes methyl, amino or aminogroup;

R16denotes hydrogen or C1-4-alkyl or-alkoxygroup;

X represents N or CR17where R17denotes hydrogen or halogen;

Y and Z independently represent the carbon atoms or nitrogen defining adjacent atoms of a five - and six-membered cycle, which is unsubstituted or substituted in one or more of the provisions oxo-, halide, methyl or halogenosilanes groups.

20. Tablet p in which the election SOH-2 inhibitor selected from the group consisting of celecoxib, deracoxib, valdecoxib, parecoxib, rofecoxib, etoricoxib, 2-(3,5-differenl)-3-[4-(methylsulphonyl)phenyl]-2-cyclopenten-1-it, (S)-6,8-dichloro-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid, 2-(3,4-differenl)-4-(3-hydroxy-3-methyl-1 butoxy)-5-[4-(methylsulphonyl)phenyl]-3-(2H)-pyridazinone and their salts.

21. Pill is and according to claim 3, in which the drug is an agent used for the treatment and/or prevention of sexual dysfunction.

22. The tablet according to item 21, where the agent is selected from the group consisting of PDE5 inhibitors, activators zaklamp, α-adrenergic antagonists and dopaminergic agonists.

23. The tablet according to item 21, in which the agent is a compound of formula

or its pharmaceutically acceptable salt,

where R1, R2and R3identical or different, denote H, C1-6-alkyl (possibly phenylselenenyl)3-5alkenyl or quinil or3-10-cycloalkyl, or where R3as mentioned above, and R1and R2cyklinowanie associated with the N atom, in the form pyrrolidinyloxy, piperidinyloxy, morpholinium, 4-methylpiperazine or imidazolinones groups;

X denotes H, F, Cl, Br, I, HE, C1-6-alkyl or-alkoxygroup, CN, carboxamide, carboxyl or (C1-6alkyl)carbonyl;

And denotes CH, CH2, CHF, CHCl, CHBr, CHI, SNSN3, C=O, C=S, CSCH3, C=NH, CNH2, CNHCH3, CNHCOOCH3, CNHCN, SO2or N;

In denotes CH, CH3, CHF, CHCl, CHBr, CHI, C=O, N, NH or NCH3n is 0 or 1;

D represents CH, CH3, CHF, CHCl, CHBr, CHI, C=O, OH, N, NH or NCH3.

24. The tablet according to item 21, in which the agent is a combination fo the mules

where will Chobotnice O or S, or its pharmaceutically acceptable salt.

25. The tablet according to claim 1, which is suitable for oral administration.

26. The tablet according to claim 1, which is suitable for intraoral administration.

27. The tablet according to claim 1, in which the shell is present in a quantity representing a weight gain from about 0.1 to about 5%.

28. The tablet according to claim 1, in which the Gellan gum is from about 25 to 100% of the weight of the shell.

29. The tablet according to claim 1, in which the Gellan gum is from about 50 to 100% of the weight of the shell.

30. The tablet according to claim 1, in which the shell further comprises at least one additional filler selected from the group consisting of buffering agents, plasticizers, dispersing and emulsifying agents.



 

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SUBSTANCE: invention describes antibody and its fragments neutralizing rabies virus and a method for treatment of patient subjected for effect of rabies virus by using indicated antibody and its fragment. Invention discloses variants of isolated nucleic acids encoding polypeptides carrying light and heavy chain of antibody, respectively. Also, invention describes expressing vector carrying at least one of indicated nucleic acids. Using this invention enhances span-life of patients after effect with rabies virus on them and can be used in corresponding prophylactic therapy of such patients.

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1 ex

FIELD: veterinary science.

SUBSTANCE: invention involves the combined use of antibacterial preparations and immunomodulator. Method involves complex of single and double RNA sodium salts from killer yeast Saccharomyces cerevisiae as an immunomodulator and synthetic polymer-carrier taken in the dose 0.3-0.4 mg/kg. Immunomodulator is administrated in animals in a single dose before onset of critical period, i. e. in 15-20 days of piglets growing. Method provides stimulation of factors of cellular and humoral immunity of animals without adverse reactions and complication due to selection of optimal dose of immunomodulator and its prolonged effect.

EFFECT: improved method for treatment and prophylaxis.

3 cl, 4 tbl, 3 ex

FIELD: medicine, virology, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a synergetic composition comprising azidothymidine and glycyrrhizic acid penta-O-nicotinate - niglizine taken in physiologically blood concentrations: 0.0037-0.0254 mcM for azidothymidine and 0.0052-9.64 mcM for niglizine. Using the proposed composition provides effective inhibition of HIV-1 reproduction and significant reducing consumptions required for treatment. The composition shows high bioavailability and high effectiveness.

EFFECT: improved and valuable medicinal properties of composition.

6 tbl, 1 dwg

FIELD: veterinary science.

SUBSTANCE: invention proposes a preparation for treatment and prophylaxis of mastitis in cows at onset of the lactation period and in dry cows that comprises the following components, wt.-%: furacrylin, 0.4-0.6; dioxydin, 0.8-1.2; bee wax, 4-6, and sunflower oil, the balance. The preparation is heated to 38-40°C and administrated in cow mammary gland being in damaged and healthy lobules of udder through a nipple duct by using a syringe in the dose 5 ml. Using the preparation provides enhancing therapeutic and prophylactic effectiveness, decreasing labor intensity in treatment and prophylaxis of mastitis in cows at the lactation period and in dry cows.

EFFECT: enhanced and valuable properties of preparation.

3 tbl, 3 ex

FIELD: veterinary science.

SUBSTANCE: invention proposes a preparation for treatment and prophylaxis of mastitis in cows at onset of the lactation period and in dry cows that comprises the following components, wt.-%: furacrylin, 0.4-0.6; dioxydin, 0.8-1.2; bee wax, 4-6, and sunflower oil, the balance. The preparation is heated to 38-40°C and administrated in cow mammary gland being in damaged and healthy lobules of udder through a nipple duct by using a syringe in the dose 5 ml. Using the preparation provides enhancing therapeutic and prophylactic effectiveness, decreasing labor intensity in treatment and prophylaxis of mastitis in cows at the lactation period and in dry cows.

EFFECT: enhanced and valuable properties of preparation.

3 tbl, 3 ex

FIELD: pharmacy.

SUBSTANCE: invention relates to metronidazol-base antiprotozoan preparation possessing broad spectrum of action with respect to protozoa. Proposed agent is made as tablets based on metronidazol and comprises polyvinylpyrrolidone, filling agent and powdering agent also. Microcrystalline cellulose is used as a filling agent, and a mixture of cross-linked homopolymer of N-vinyl-2-pyrrolidone with the nitrogen content 11-12.8% and poly-(2-oxypyrrolidine-1-ylethylene) with K- viscosity value 22.5-26.7 and taken in the ratio = (1-5):1, respectively, is used as polyvinylpyrrolidone. Invention provides enhancing strength of tablet in combination with its rapid degradation in water.

EFFECT: improved pharmaceutical properties of agent.

1 tbl

FIELD: medicine, organic chemistry, pharmacy.

SUBSTANCE: invention relates to an antibacterial preparation based on α-aminosulfonic acid amide, i. e. N'-methyl-1-phenyl-1-N,N-diethylaminomethanesulfonamide that can be used in veterinary science. Invention relates to expanding assortment of agents used against pathogenic pathogen with a preparation relating to class of α-aminosulfonic acid amides eliciting antibacterial activity being without cumulative properties and pathological changes in animal organs and tissues.

EFFECT: valuable veterinary properties of preparation.

1 tbl, 1 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to synthesis of new polyelectrolytes of cationic type based on diallylamine trifluoroacetate representing monomers of order both N,N-diallylamine and N,N-diallyl-N-methylamine. Invention describes polydiallylamines of the general formula: wherein R means hydrogen atom (H), -CH3; n = 107-308 (weighted mean degree of polymerization); molecular mass = 24000-65000 g/mole (weighted mean molecular mass); width of molecular-mass distribution δ = 1.85. Their aqueous solution can be used as a disinfecting agent in the minimal inhibitory concentration from 1.25 x 10-4 g/ml to 1.5 x 10-6 g/ml. Invention can be used in different branches of industry, in particular, in medicine.

EFFECT: valuable properties of compounds.

2 cl, 5 tbl, 4 dwg, 2 sch

FIELD: medicine.

SUBSTANCE: method involves incubating antibiotics and/or chemopreparations in therapeutic doses with autoplasma 30 min at 37°C and introducing the preparations into paravaginal cellular tissue to patients suffering from genitalia diseases and into paravesical cellular tissue to patients suffering from urinary bladder diseases and into pararectal cellular tissue to patients suffering from rectum diseases. Tumor proliferation into neighboring small pelvis organs (into paravaginal and/or pararectal and/or paravesical cellular tissue) taking place, the treatment is applied twice a week.

EFFECT: increased pathological focus regression percent; reduced manifestations of drug therapy complications.

Muscarinic agonists // 2269523

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compounds of the general formula (I): wherein Z1 represents -CR1 or nitrogen atom (N); Z2 represents -CR2; Z3 represents -CR3 or N; Z4 represents -CR4; W1 represents oxygen (O), sulfur (S) atom or -NR5; one of W2 and W3 represents N or -CR6 and another among W2 and W3 represents CG; W1 represents NG; W2 represents -CR5 or N; W3 represents -CR6 or N; or W1 and W3 represent N and W2 represents NG; G represents compound of the formula (II): wherein Y represents oxygen atom (O), -C(O)- or absent; p = 1, 2, 3, 4 or 5; Z is absent; each t = 2. Also, invention describes a method for enhancing activity of the muscarinic cholinergic receptor and a method for treatment of morbid states when modification of cholinergic and, especially, muscarinic receptors m1, m4 or both m1 and m4 offers the favorable effect.

EFFECT: valuable medicinal properties of agonists.

14 cl, 2 tbl, 101 ex

FIELD: medicine, ophthalmology.

SUBSTANCE: the present innovation deals with introducing medicinal preparation onto scleral bottom and episclerally at the end of operation. As medicinal preparation one should apply 50%-glycerol solution, onto scleral bottom and episclerally introduced per 1 drop of solution. Exposure of glycerol solution corresponds to 1-2 min. The innovation enables to decrease the quantity of complications in post-operational period.

EFFECT: higher efficiency of therapy.

2 cl, 2 ex

FIELD: medicine.

SUBSTANCE: method involves per os introducing lipoic acid concurrently with beta-carotene at a dose of 0.05 and 10 mg 3 times a day during 1 month, respectively.

EFFECT: enhanced effectiveness of treatment; improved antioxidation activity in eye tissues; improved vision function.

3 dwg, 1 tbl

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to 1-ethanolamide PGF of formula I useful in relaxation of mammalian intraocular pressure. Claimed substance unlike majority of ocular hypotensive prostaglandins doesn't effect through FP-receptor.

EFFECT: new effective compound for relaxation of mammalian intraocular pressure.

4 cl, 1 ex, 16 dwg, 16 tbl

The invention relates to the creation of homeopathic remedies and can be used in the conservative treatment of glaucoma with medication or surgically normalized and normal intraocular pressure

The invention relates to imidazole derivative of the formula (I), where X, Y, R, R2, R3and R4such as defined in the claims

The invention relates to imidazole derivative of formula (1), where X, Y, R, R2, R3and R4such as defined in the claims

The invention relates to the field of medicine and relates to a composition for topical application, reducing intraocular pressure, comprising the antagonist of angiotensin II, boric acid and ethylenediaminetetraacetic acid

The invention relates to the field of medicine and organic chemistry and relates to new derivatives of prostaglandin F-type used as an ocular hypotensive drugs, as well as to a method of treatment of glaucoma with their help, ophthalmic solutions and kits comprising these solutions

The invention relates to new indole derivative of the formula I

< / BR>
where R denotes ethyl or 2,2,2-triptorelin group; Y is hydroxy or pivaloyloxy; the carbon atom marked with the symbol (R) is the carbon atom in (R)-configuration, or its pharmaceutically acceptable salts

FIELD: medicine.

SUBSTANCE: method involves administering drugs usable for hindering keratoleukoma occurring after carrying out excimer laser keratectomy with an antioxidant agent being added. The agent is used for jet irrigating cornea before setting lens.

EFFECT: enhanced effectiveness in reducing lipid peroxidation products quantity; accelerated cornea epithelialization.

2 cl, 2 tbl

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