• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    A pharmaceutical mixture with controlled release of actice substance which includes masking of bad taste and stability increasing of active substance characterized in that an encapsulated active substance is combined with a substance controlling the release of active substance from the encapsulation and method for preparing said mixture.
    公开号:SU1722207A3
    申请号:SU833607650
    申请日:1983-06-23
    公开日:1992-03-23
    发明作者:Геран Вильхельм Кельстранд Андерс；Иохан Маттссон Кельл
    申请人:Астра Лекемедель Актиеболаг (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to the pharmaceutical and pharmaceutical industry and relates to a method for the manufacture of agents for oral administration.
    The aim of the invention is to increase the stability of the target product.
    Example. 100 g of anhydrous powder contain, g: bacampicillin hydrochloride, in the form of microcapsules of ethyl cellulose (70% of the drug) 5.61; sodium bicarbonate 0.83; mannitol 9.35; sucrose 83.1.
    Sodium bicarbonate, mannitol and sucrose are pre-mixed before adding the microcapsules. Final mixing is carried out in a beaker. The resulting mixture contains 46% by weight (mass substrate regulating the separation process). 4.81 g of powder is added to 5 ml of water. The results are shown in table 1 and 2.
    Leakage of the drug is analyzed by the method of mercurimetric titration,
    PRI mme R 2. 25.8 g of the pharmaceutical mixture contain g: bacampicillin hydrochloride EudragitK E 100 microcapsules (64%) of the drug preparation 0.80; fructose 18.75; water 6.25.
    Fructose is dissolved in water before the microcapsules are added.
    The resulting mixture contains 67.5% of the substances controlling the release of drugs. The results are shown in table 3.
    PRI me R 3. 31.3 g of a pharmaceutical mixture contains, g: theophylline, ethylcellulose microcapsules (72% of the drug) 0.05; fructose 23.44 and water 7.82, or sorbitol 20.94 and water 7.82.
    These two mixtures were prepared according to Example 2. The mixtures contain 75 and 72% of the substance, respectively.
    regulatory, regulatory release of the drug. The results are summarized in table 4.
    PRI me R 4. 31.3 g of the pharmaceutical mixture will hold in, g: theophylline, ethyl cellulose-5-microzcapsules (72% of the drug) 0.05; sucrose 9.38 and sorbitol 9.38; sucrose 9.38 and glycerin 9.38; glucose 9.38, fructose 9.38 and water 12.5.
    These three mixtures are obtained according to example 2, 10
    Mixtures contain 60% of the substances that regulate the release of drugs. The results are shown in table.5.
    PRI me R 5. 75.1 of the pharmaceutical mixture contains, g: acetylsalicylic acid, 15 lots, microcapsules of cellulose acetate phthalate (69% of the drug) 0.1; sucrose 48.75; phosphate buffer solution (pH 7.0) 26.25.
    The sucrose is dissolved in a phosphate bupurm solution and then the microcapsules are added.
    The resulting mixture contains 65% of the substance that regulates the release of the drug. The results are summarized in 25 table.6.
    EXAMPLE 6 The mixtures listed in Table 7 are prepared as in Example 1, with mixture 1 containing 44% of the substance that regulates the release of the drug.
    Isolation of microcapsules in water is similar to that shown in Example 1. The test results are shown in Table 8.
    Example. Four different 35 microcapsules coated with ethyl cellulose are suspended in sorbitol dissolved in water in accordance with the following composition: microcapsules 50 mg; sorbitol 45.1 g; water 19.3 g., 40
    The mixture thus obtained contains 70% of the substance that regulates the release of the drug. The data are given in table.9.
    PRI me R 8. 0.2 g of theophylline microcapsules obtained in accordance with Example 3 are suspended in various sugar solutions. Test data are given in table 10.
    Thus, it is possible to limit the leakage of the mixture to only a few percent after a storage period of three months at room temperature.
    PRI me R 9. 65.4 g of a pharmaceutical 55 mixture contain, g: theophylline, wax-coated, microcapsules (52% of the drug) 1; sorbitol 45.1; water 19.3.
    This mixture is prepared in accordance with Example 3.
    The mixture contains 69% of the substance that regulates the release of the drug. Test data are given in table 11.
    Example 0.26.31 g of a pharmaceutical mixture contains: prochlorperazin, coated with wax, in the form of microcapsules (3.4% of the drug) 10 mg; sorbitol 18 g; water 8.3 g
    This mixture was prepared in accordance with Example 3. The mixture contains 70% of the substance that regulates the release of the drug: The test data are given in Table 12.
    Example 11.27,15 g of a pharmaceutical mixture contains, g: ethyl cellulose coated theophylline microcapsules (72% of the drug) 0.15; polyethylene glycol (carbowax-400) 20.25; water 6.75.
    The polyethylene glycol is mixed with water and then the microcapsules are added. The resulting mixture contains 75% of the substance that regulates the release of the drug. The leakage is 2.4% in 15 days. Data concerning excretion in water is indicated in example 3.
    PRI me R 12. 13,877 g of the pharmaceutical mixture contain: erythromycin, microcapsules coated with cellulose acetate phthalate (57% of the drug) 0.877 mg; fructose 9.75 g; water 3.25 g
    The resulting microcapsules are added to a solution of fructose in water. The resulting mixture contains 71% of the substance controlling the release of the drug. Test data are summarized in table 13,
    Examination of the selection process.
    Microcapsules are suspended in a 75% solution of a substance that regulates drug release. After two or three days of storage, the microcapsules are filtered and the release of the drug is measured.
    Microcapsules are placed in a beaker containing either gastric juice (modeled) or intestinal (intercellular) fluid (modeled) at 37 ° C in order to simulate a situation in a living organism. The process is carried out with stirring at a speed of 30 rpm. Samples were taken after certain periods of time and analyzed for the content of the drug using the spectrometry method. The results indicate the time during which 50, 70 and 90% of the total amount of the drug contained in the microcapsules is released (Table 14).
    Formula and method of manufacturing an agent for oral administration by mixing the encapsulated active substance with a substance to control the release of the active substance, in order to increase the stability as active substance added
    are encapsulated bacampicillin hydrochloride or theophylline, or acetylsalicylic acid, and as a substance to control the release of the active substance - sucrose, glucose, fructose, xylitol, sorbitol or a mixture with mannitol, glycerin, sorbitol, pre-solution of them in water in the amount of 60-90% of the whole composition.
    Table
     Percentage release data in water
    ABOUT
    table 2
    Table 3
    Table 4
    These emissions in water are in percent.
    Data leakage in percent.
    Table 5
    Table 6
    Table 7
    Water excretion in percent.
    1722207
    10 Table 8
    Table 9
    Table 10
    Table 11
    eleven
    Percentage in water,
    Water excretion in percent.
    1722207
    12 Table 12
    Table 13
    Table 14
    权利要求:
    Claims (1)
    [1]
    Claim
    A method of manufacturing an agent for oral administration by mixing the encapsulated active substance with a substance for controlling the release of the active substance, characterized in that, in order to increase stability, encapsulated bacampicillin hydrochloride or theophylline or acetylsalicylic acid is added as the active substance; as a substance for regulating the release of the active substance - sucrose, glucose, fructose, xylitol, sorbitol or a mixture with mannitol, glycerin, sorbitol, precede no dissolving them in water in an amount of 60-90% of the total composition.
    1 table!
    Time days A leak, % 1 0.5 2 0.9 4 1,1 7 1.3 10 1,2
    table 2
    Time days Isolation in water,% I 0,042 60 0,084 90 I
    Table 3
    Time h A leak, % 2 Less than 0.2 0.008 fifty 0.05 90
    Table 4
    Time days Leakage,%, mixtures with fructose sorbitol 1ABOUT Less than 0.2 0.7 5 η_ _ 7 Less than 0.2 - 10 - ”- - 0.21 fifty* - 0.33 90 * -
    * The data of the allocation in water as a percentage
    Table 5
    Time days Leakage,%, mixed with sucrose and sorbitol sucrose and glycerin glucose, fructose and water 1 0.20 Less than 0.2 0.26 2 0.31 0.35 0.28 5 0.65 0.82 0.49 9 1.15 1.77 0.90 0.21 fifty*0.33 90 *
    The data of the allocation in water as a percentage.
    Table 6
    Time days Isolation in phosphate buffered saline (PH 7.0),% 1 3.5 * 0.008 fifty 0.017 90 I
    Percentage leakage data.
    Table 7
    Components The content of components, t, in the mixture 1 2 3 Bakampicillin hydrochloride, ethyl cellulose microcapsules (70% of the drug) 0.27 0.27 0.27 Bicarbonate of soda 0.40 0.40 Mannitol 0.45 - - Sucrose 4.0 - - Water 5,0 5,0 5,0
    Table 8
    Time days Leakage,%, in the mixture 1 2 3 1 0.5 85 100 2 0.94 1.17 1.310 1.2
    Table 9
    Microcapsule The content of the active drug in the microcapsule Leak in sorbitol drug-regulating substance Isolation in Water % Days % h KCI 86 16 21 ' 56 3 Paracetaminophen non 91 19 21 35 1 Flucloxacillin 89 20 1 90 0.5 Phenoxymethyl penicillin ca- Liy 83 10 1 80 1
    Table 10
    The substance that regulates the release,% A leak, % Time days Xylitol 45Glucose 50Sorbitol 70Fructose 75Fructose Xylitol 19-41Fructose-Xylitol 38-28Fructose Xylitol 56-14 13 17 331064 808080808080
    Table 11
    Time days A leak, % 22 0.7 0.5 19*
    The allocation in water as a percentage.
    Table 12
    Time days A leak, % 12 2.7 0.25 28 *
    * Isolation in water as a percentage.
    Table 13
    Time days A leak, % 10 Less than 1 0.25 46 *
    * Isolation in water as a percentage.
    Table 14
    You division,% Simulated gastric juice, h Simulated Intenstinal Fluid, h Source 3 days later Source 3 days later fifty 4.2 4.4 3,7 4.4 70 5.7 5.8 5.5 6.6 90 6.2 6.4 7.5 8.3
    类似技术:
    公开号 | 公开日 | 专利标题
    SU1722207A3|1992-03-23|Method of remedy preparation for oral administration
    KR880001752B1|1988-09-12|Process for preparing a dry powder for use as a pharmaceutical mixture
    US4994260A|1991-02-19|Pharmaceutical mixture
    US5708017A|1998-01-13|Stable, ready-to-use pharmaceutical paste composition containing proton pump inhibitors
    ES2529570T3|2015-02-23|Multiparticulate formulations of pantoprazole
    FI78835C|1989-10-10|FOERFARANDE FOER FRAMSTAELLNING AV EN NY DIPYRIDAMOL-RETARDFORM.
    US3903297A|1975-09-02|Method of treatment and prophylaxis of gastric hypersecretion and gastric and duodenal ulcers using prostaglandin analogs
    US4160827A|1979-07-10|Metronidazole phosphate and salts
    ES2314227T7|2012-11-19|ORAL PHARMACEUTICAL FORMULATION IN THE FORM OF A WATERPROOF SUSPENSION OF MICROCAPSULES THAT ALLOW THE MODIFIED RELEASE OF AMOXYLYCIN.
    US3131123A|1964-04-28|Enteric tablets and manufacture thereof
    US3898328A|1975-08-05|Dry stable composition for the treatment of scours and dehydration
    RU2733950C1|2020-10-08|Combination for treating prostate cancer, a pharmaceutical composition and a method of treating
    DK161185B|1991-06-10|PHARMACEUTICAL PRODUCT BASED ON VALPROIC ACID
    EA014451B1|2010-12-30|Pharmaceutical compositions containing rosuvastatin calcium
    BG63708B1|2002-10-31|Medicamentous tramadol forms
    JPH0816051B2|1996-02-21|Sustained release suppositories
    SE447871B|1986-12-22|PHARMACEUTICAL COMPOSITION WITH LONG EXCEPTION TIME INCLUDING PINACIDIL IN AT LEAST TWO DIFFERENT TYPES OF PELLETS
    US3144387A|1964-08-11|Anti-inflammatory compositions
    JPH01128932A|1989-05-22|Galenical form of coturnix ovum and its production
    GB630439A|1949-10-13|Improvements in or relating to pharmaceutical preparations
    US4223008A|1980-09-16|Slow release pharmaceutical compositions containing 3-[2-|ethyl]indole, embonate
    US2846352A|1958-08-05|Vitamin compositions and method for producing the same
    RU2731535C1|2020-09-04|Combination, use thereof and method of treating
    US3000874A|1961-09-19|Sulfate salt of erythromycin monoester
    US3296074A|1967-01-03|Methods and compositions for treating psychoses and neuroses
    同族专利:
    公开号 | 公开日
    KR840005024A|1984-11-03|
    EP0101418A3|1984-11-14|
    ZA833931B|1984-07-25|
    DD209971A5|1984-05-30|
    JPH0559089B2|1993-08-30|
    EP0101418A2|1984-02-22|
    NO168745B|1991-12-23|
    NO168745C|1992-04-01|
    DK161365B|1991-07-01|
    SE8203953D0|1982-06-24|
    PT76919A|1983-07-01|
    HK98786A|1986-12-24|
    DE3382086D1|1991-02-07|
    GB2122490B|1986-04-03|
    FI85213C|1992-03-25|
    GB2122490A|1984-01-18|
    GR78604B|1984-09-27|
    HU189300B|1986-06-30|
    CY1468A|1989-07-21|
    JPS5916822A|1984-01-28|
    AU1594383A|1984-01-05|
    FI832197L|1983-12-25|
    DK272383D0|1983-06-14|
    CS257769B2|1988-06-15|
    FI832197A0|1983-06-16|
    MY8700292A|1987-12-31|
    AR231075A1|1984-09-28|
    IS2824A7|1983-12-25|
    EP0101418B1|1990-12-27|
    PT76919B|1986-04-09|
    DK272383A|1983-12-25|
    CA1214726A|1986-12-02|
    PH21911A|1988-04-08|
    CS463683A2|1987-11-12|
    ES8403720A1|1984-04-01|
    KR910000028B1|1991-01-19|
    IS1325B6|1988-08-03|
    FI85213B|1991-12-13|
    AU561954B2|1987-05-21|
    AT59286T|1991-01-15|
    GB8317071D0|1983-07-27|
    BG51341A3|1993-04-15|
    NO832293L|1983-12-27|
    ES523536A0|1984-04-01|
    NZ204639A|1986-01-24|
    IE55204B1|1990-07-04|
    DK161365C|1991-12-09|
    IE831462L|1983-12-24|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    BE636568A|1961-01-31|
    US3689654A|1970-09-14|1972-09-05|Morton Norwich Products Inc|Pharmaceutical compositions|
    GB1506016A|1974-02-22|1978-04-05|Wellcome Found|Pharmaceutical preparations|
    SE8003805L|1980-05-21|1981-11-22|Haessle Ab|A PHARMACEUTICAL PREPARATION WITH IMPROVED EMISSION PROPERTY|
    US4321253A|1980-08-22|1982-03-23|Beatty Morgan L|Suspension of microencapsulated bacampicillin acid addition salt for oral, especially pediatric, administration|
    SE8103843L|1981-06-18|1982-12-19|Astra Laekemedel Ab|PHARMACEUTICAL MIXTURE|
    JPS57209223A|1981-06-19|1982-12-22|Tanabe Seiyaku Co Ltd|Microcapsule for intracranial anti hypotension and its production|JPH0729927B2|1983-04-09|1995-04-05|日研化学株式会社|Theophylline sustained release formulation|
    SE8405611D0|1984-11-09|1984-11-09|Astra Laekemedel Ab|PROCESS FOR STABILIZATION OF BACAMPICILLIN HYDROCHLORIDE|
    IT1183575B|1985-05-08|1987-10-22|Eurand Spa|FORMULATION DEODORING WITH MODULATING EFFECT ON TRANSPIRATION|
    NL8503539A|1986-01-02|1987-07-16|Warner Lambert Co|SUCROSE-FREE PREPARATIONS.|
    US4780320A|1986-04-29|1988-10-25|Pharmetrix Corp.|Controlled release drug delivery system for the periodontal pocket|
    SE8605515D0|1986-12-22|1986-12-22|Astra Laekemedel Ab|A LIQUID DOSAGE FORM FOR ORAL ADMINISTRATION OF A PHARMACEUTICALLY ACTIVE SUBSTANCE|
    US4874613A|1987-03-06|1989-10-17|Baker Cummins Pharmaceuticals, Inc.|Taste concealing pharmaceutical dosage unit|
    US5427935A|1987-07-24|1995-06-27|The Regents Of The University Of Michigan|Hybrid membrane bead and process for encapsulating materials in semi-permeable hybrid membranes|
    SE463542B|1987-08-31|1990-12-10|Lejus Medical Ab|GRANULATED INSTANTIZABLE PRODUCT AND PROCEDURES FOR ITS PREPARATION|
    WO1989010117A1|1988-04-19|1989-11-02|Southwest Research Institute|Controlled release of active ingredients from capsules having a salt sensitive shell material|
    US5064650A|1988-04-19|1991-11-12|Southwest Research Institute|Controlled-release salt sensitive capsule for oral use and adhesive system|
    FR2653337B1|1989-10-23|1992-02-07|Dow Corning Sa|SUSTAINED RELEASE ELEMENT AND METHOD FOR MANUFACTURING THE SAME.|
    CA2068402C|1991-06-14|1998-09-22|Michael R. Hoy|Taste mask coatings for preparation of chewable pharmaceutical tablets|
    US5364634A|1991-11-08|1994-11-15|Southwest Research Institute|Controlled-release PH sensitive capsule and adhesive system and method|
    DE4200821A1|1992-01-15|1993-07-22|Bayer Ag|TASTE-MASKED PHARMACEUTICAL AGENTS|
    JP3265680B2|1992-03-12|2002-03-11|大正製薬株式会社|Oral pharmaceutical composition|
    DE4312656C2|1993-04-19|1996-01-25|Beiersdorf Ag|Cooling cosmetic or dermatological compositions|
    DE4423078B4|1994-07-01|2005-01-13|Awd.Pharma Gmbh & Co. Kg|A process for the preparation of a sustained-release carbamazepine dosage form|
    CN1170596C|1995-05-02|2004-10-13|大正制药株式会社|Composition for oral administration|
    DE19706978A1|1997-02-21|1998-08-27|Ulrich Dr Posanski|Combination preparation for oral antibiotics|
    US7943585B2|2003-12-22|2011-05-17|Sandoz, Inc.|Extended release antibiotic composition|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    SE8203953A|SE8203953D0|1982-06-24|1982-06-24|PHARMACEUTICAL MIXTURE|LV930693A| LV5391A3|1982-06-24|1993-06-28|A drop in peroral is given for the preparation of a medicament|
    LTRP946A| LT2252B|1982-06-24|1993-09-06|THE ORAL MEDICINAL PRODUCT MANUFACTURE|
    [返回顶部]