• 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:
    This invention relates to the chemical and pharmaceutical industry and relates to a process for the production of nicorandil. The purpose of the invention is to increase stability. Nicorandil is mixed with an organic acid: fumaric or tartaric in a certain amount, saturated with higher aliphatic acid: palmitic or stearic or saturated higher alcohol, namely cetyl or stearyl in an amount of not less than 0.5% of the total mass, passed through a sieve to obtain granules and tableted. 3 tab.
    公开号:SU1687022A3
    申请号:SU874028833
    申请日:1987-01-16
    公开日:1991-10-23
    发明作者:Иида Есимицу；Сумида Судзи
    申请人:Чугаи Сейяку Кабусики Кайся (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to the chemical and pharmaceutical industry and relates to a process for the production of nicorandil.
    The aim of the invention is to increase stability.
    Example 1. The composition of one tablet mg: Nicorandil10
    Stearic acid8
    Mannit65,7
    Corn starch15
    Methyl Cellulose 0.3
    Magnesium Stearate 1
    Total100.0
    Mannitol (65.7 g), corn starch (15 g) and methylcellulose M-400 (0.3 g, produced by Sintets Chemical Industrial Industry) are thoroughly mixed in a mortar and mastered with the addition of water. The mixture is passed through a 30 mesh sieve and dried for 3 hours at 45 ° C. The dried particles are dispersed by passing through a 30 mesh sieve to form granules.
    Nicorandil (10 g), stearic acid, sifted through a 35 mesh sieve (8 g), granules (81 g) and magnesium stearate (1 g) are mixed in a plastic bag, and the mixture is pressed under a pressure of 2000 kg / cm2. form (7 mm) to obtain tablets weighing 100 mg.
    Comparison tablets are prepared under the same conditions, but with the exception that stearic acid is replaced by the same amount of mannitol.
    Each of the two groups of tablets is divided into two subgroups. The tablets of one subgroup are vacuum dried to substantially dehydrate them, and the tablets of another subgroup remain undehydrated. All tablets are then placed in glass vials, covered with screw caps and stored at 40 ° C for 3 months. The stability of the tablets is assessed by the residual amount of nicorandil, calculated as a percentage of the initial mass before acceleration.
    The results are shown in table 1. Example 2 The composition of one tablet mg:
    s
    -her
    J
    about
    00
    3
    SO 43
     jJ
    Nicorendil10
    Stearic alcohol 10
    Mannit72,4
    Carboxymethylcelluloseacquisition5
    Hydroxypropylcellulose1, 6 Calcium stearate 1 Total 100.0 Stearyl sprint (South), passed through a 35 mesh sieve, mannitol (72.4 g), carboxymethylcellulose (B g) and hydroxypropylcellulose HPC-L (1.6 g, manufactured by Yippon soda) is thoroughly mixed in a mortar and mastirated with water. The mixture is passed through a 30 mesh sieve and dried for 5 hours at 40 ° C. The dried particles are sieved by passing through a 30 mesh sieve to obtain granules.
    Nicorandil (10 g), granules (89 g) and 100 a calcium stearate (1 g) are mixed in a plastic bag, and the mixture is pressed at 2000 kg / cm2. In a mold (07 mm) to make tablets weighing 100 mg each .
    Example 3. The composition of one tablet mg: Nicorandil10
    Palmitinova
    acid3
    Lactose 82
    Crosscarmellose sodium5
    TotalU, O
    Nicorandil (10 g), palmitic acid 1 (3 g), crushed to an average particle size of 1-3 μm in a microjet mill (FS-4 model manufactured by Seysin Kige), lactose (82 g) and crosscarmelocellulose sodium (5 g. Ac -Di-Sol manufactured by FMS) is mixed in a plastic bag. The mixed powder is pressed at 2000 kg / cm 2 in a mold (07 mm) to obtain tablets weighing 100 mg each. The results are shown in table 2. Example 4. The composition of the pill mg mg; Nikorandil10
    Stearinova
    acid16
    Lactose85
    Crosscarmelloz sodium 8
    Corn Starch1.0
    Total100.0
    Stearic acid (16 g), lactose (85 g) and crosscarmellose sodium (V g, Ac-DI - So K manufactured by FMS) are mixed in a mortar and then mastered with 20 g of 5% corn starch paste. The mixture is sifted through a 30 mesh sieve and dried at 45 ° C for 4 hours. The dried particles are classified by passing through a 30 mesh sieve to obtain a granulate.
    Granules (90 g) and nicorandil (10 g) are mixed in a plastic bag, and the mixture is pressed at 2000 kg / cm2 in a mold (Ј1 mm) to obtain tablets weighing 100 mg each.
    Example 5. The composition of one tablet mg:
    Nikorandil10
    0 Lactose 65,5
    Stearinova
    acid8
    Krosskarmelloeanatrii5
    5 Fumarova
    acid10
    Corn
    starch1
    Magnesium stearate 0.5
    0 Total 100.0
    Lactose (65.5 g), stearic acid (8 g) and crosscarmellose sodium (5 g, Ac-Di-SolR manufactured by FMS) are mixed in a mortar, then mastered with 20 g of 5% 5 corn starch paste, the mixture is sieved through 30 mesh sieve and dried for 4 hours at 45 ° C. The dried particles are classified by passing through a 30 mesh sieve to obtain a granulate.
    0 Nicorandil (10 g), fumaric acid (10 g), granulate (79.5 g) and magnesium stearate (0.5 g) are mixed in a plastic bag.
    Using a single punch tabletting machine equipped with a 5 mm 7 mm punch with a flat end, the mixed powder is pressed to a total pressure of about 1 ton to form tablets weighing 100 mg each.
    Example 6. The composition of the drug in the capsule - 0 groin (per 1 pc), mg:
    Nikorandil10
    Mannit40
    Fumarova
    acid10
    5 Stearyl
    alcohol 30
    Carboxymethyl-ethylcellulosecalcium 10
    Total100.0
    0 Nicorandil (10 g), mannitol (40 g), fumaric acid (10 g), Stearyl alcohol (30 g) and carboxyl cellulose calcium (10 g) are mixed in a mortar, and then masticated with 22 g of 20% ethanol. The mixture is sieved through a 14 mesh sieve and dried for 6 hours at 40 ° C. The dried particles are classified by passing through a 10 mesh sieve to obtain gr.
    Example 7. The composition of the tablet preparation (per 1 item), mg:
    Nikorandil10
    Mannit52
    Salicylov
    acid5
    Palmitinova
    acid2
    Corn
    starch10
    Crystal
    cellulose 20
    Calcium stearate 1
    Total100.0
    Nicorandil (10 g), mannitol (52 g), salicylic acid (5 g), palmitic acid (2 g), corn starch (10 g), crystalline cellulose (20 g), and calcium stearate (1 g) are mixed in a plastic bag.
    Using a single-punch tabletting machine equipped with flat-ended T mm punch pins, the mixed powder is compressed under a load of 1 ton to obtain tablets weighing 100 mg each.
    Example 8. Composition of a preformed preparation with a low release rate of the active substance (per unit), mg:
    . Nicorandil (10 g), fumaric acid (85.5 g), stearic acid (4 g) and calcium stearate (0.5 g) are mixed in a plastic bag to obtain a mixture (mixed powder A). Separately, fumaric acid (39.8 g) and calcium stearate (0.2 g) are mixed in a plastic bag to obtain a mixture (mixed powder B).
    Using a single punch tabletting machine equipped with punches in mm with flat ends, mixed powder A (100 mg) is filled into the matrix and lightly pressed, Then mixed powder B (40 mg) is fed to the compressed mixed powder and pressed under load 1 , 3 tons with the production of tablets with a delayed release.
    Example 9. The composition of one tablet mg:
    Nikorandil10
    Mannit63,5
    Stearinova
    acid8
    Oxalic acid12
    Carboxymethylcellulose5
    Corn
    starch1
    Calcium stearate 0.5
    Total100
    Mannitol (63.5 g), stearic acid (8 g) and oxalic acid (12 g) are mixed in a mortar and then mixed with 5% cornstarch paste (20 g). The mixture is sieved through a 30 mesh mesh and dried at 45 ° C for 4 hours. Dry particles are classified by passing through a 30 mesh sieve and granules are obtained. Granules (84.5 g), nicorandil (10 g), carboxymethylcellulose calcium (5 g) and calcium stearate (0.5 g) are mixed in a polyethylene chamber.
    Using a single punch tablet machine equipped with mm flat dies, the mixed powder is compressed with a total pressure of 1 ton and tablets each weighing 100 mg are obtained.
    Example 10. The composition of one tablet mg:
    Nikorandil10
    Lactose 63,5
    Cetyl alcohol8
    Wine acid .12
    Lower substituted hydroxypropylcellulose5
    Hydroxypropylcellulose1
    Magnesium stearate 0.5
    Total100
    Lactose (63.5 g), cetyl alcohol (8 g) and tartaric acid (12 g) are mixed in a mortar and then mixed with a 5% aqueous solution of hydroxypropylcellulose (20 g). This mixture is passed through a 30 mesh sieve and dried at 45 ° C for 4 hours. Dry particles are classified by passing through a 30 mesh sieve and granules are obtained. These granules (84.5 g), nicorandil (10 g), lower substituted hydroxypropylcellulose kalcium (5 g) and magnesium stearate (0.5 g) are mixed in a polyethylene vessel.
    Using a single punch tablet machine equipped with mm flat dies, the mixed powder is pressed at a total pressure of 1 ton and tablets are obtained, each weighing 100 mg. Example 11. The composition of one tablet
    mg:

    10 63.5
    eight
    Glutaric acid12
    Hydroxypropyl starch5
    Hydroxypropylmethyl
    cellulose1
    Calcium stearate 0.5
    Total100
    Mannitol (63.5 g), myristic acid (8 g) and glutaric acid (12 g) are mixed in a mortar and then mixed with a 5% aqueous solution of oisipropyl methylcellulose (20 g). The mixture is sifted through a 30 mesh sieve and dried at 45 ° C for 4 hours. Dry particles are classified by passing 30 mesh through it, and granules, Granules (84, K g), nicorandil (10 g), oxypropyl starch (5 g) and Calcium stearate (0.5 g) is mixed in a polyethylene vessel.
    Comparative (ablettes are obtained under the same conditions, except that the mystrinoic and glutaric acids are replaced by different amounts of mannitol.
    Each of the two groups of tablets is placed in glass vessels and stored under accelerated conditions at 40CC. One set of these groups is kept for 3 months in closed vessels, while another set of these groups
    kept at a relative humidity of 61.5% 3 months with open vessels.
    The results of this stability test are shown in Table 3 through the percentage of active ingredient that remains, compared with the percentage of active ingredient subjected to accelerated conditions.
    The proposed method provides an increase in stability, as compared with the known method, not only in wet conditions, but also when pelletizing under a press.
    权利要求:
    Claims (1)
    [1]
    DETAILED DESCRIPTION A method for producing nicorandil tablets by mixing with auxiliary substances, followed by granulation and tableting. characterized in that, in order to increase stability, nicorandil is mixed with an organic acid, such as fumaric or tartaric acid, in an amount of at least 0.1% and a saturated higher aliphatic acid, including palmitic or heparic acid, or a saturated higher alcohol, selected from groups that include cetyl or stearyl alcohol in an amount of not less than 0.5% of the total mass.
    Pills
    Suggested Wed avnit1 tn1e
    Table
    table 2
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    同族专利:
    公开号 | 公开日
    JP2532224B2|1996-09-11|
    DD253181A5|1988-01-13|
    ZA87279B|1987-09-30|
    JPS62252723A|1987-11-04|
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    CN102186474A|2008-08-14|2011-09-14|杏林制药株式会社|Uchida hiroshi [jp]; fukuda mamoru [jp]; aritomi seigo|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    JP772286|1986-01-17|
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