JP2002020282A - Pravastatin-containing composition - Google Patents
Pravastatin-containing compositionInfo
- Publication number
- JP2002020282A JP2002020282A JP2000196313A JP2000196313A JP2002020282A JP 2002020282 A JP2002020282 A JP 2002020282A JP 2000196313 A JP2000196313 A JP 2000196313A JP 2000196313 A JP2000196313 A JP 2000196313A JP 2002020282 A JP2002020282 A JP 2002020282A
- Authority
- JP
- Japan
- Prior art keywords
- binder
- pravastatin sodium
- pravastatin
- saccharide
- tablet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 25
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 title claims abstract 13
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 title abstract description 15
- 229960002965 pravastatin Drugs 0.000 title abstract description 15
- 229960001495 pravastatin sodium Drugs 0.000 claims abstract description 27
- 239000011230 binding agent Substances 0.000 claims abstract description 19
- 150000001720 carbohydrates Chemical class 0.000 claims abstract description 17
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 14
- 235000010355 mannitol Nutrition 0.000 claims abstract description 9
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 7
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 7
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 claims abstract description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 6
- 239000008101 lactose Substances 0.000 claims abstract description 5
- 229930195725 Mannitol Natural products 0.000 claims abstract description 4
- 239000000594 mannitol Substances 0.000 claims abstract description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 238000010998 test method Methods 0.000 claims description 6
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 5
- 238000004898 kneading Methods 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000000748 compression moulding Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- 229920003063 hydroxymethyl cellulose Polymers 0.000 abstract 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 abstract 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-M pravastatin(1-) Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC([O-])=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-M 0.000 description 29
- 239000003826 tablet Substances 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 7
- 235000019658 bitter taste Nutrition 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000012046 mixed solvent Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 239000007932 molded tablet Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 2
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 2
- 241000544066 Stevia Species 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000002610 basifying agent Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 201000001386 familial hypercholesterolemia Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、高脂血症治療剤で
あるプラバスタチンナトリウムを含有する組成物に関す
るものであり医薬分野における発明である。TECHNICAL FIELD The present invention relates to a composition containing pravastatin sodium which is a therapeutic agent for hyperlipidemia, and is an invention in the field of medicine.
【０００２】[0002]
【従来の技術】プラバスタチンナトリウムは、コレステ
ロール生合成系の律速酵素であるHMG-CoA還元酵素を特
異的・拮抗的に阻害することにより、血清コレステロー
ル値を速やかにかつ強力に低下し血清脂質を改善する高
脂血症、家族性高コレステロール血症治療剤であり、臨
床的に世界中で広く用いられている薬剤である。プラバ
スタチンナトリウムは、白色〜微灰黄白色の粉末又は結
晶性の粉末で、苦味を有している。このため治療に供さ
れる製剤、例えば細粒剤及び錠剤は高分子物質によりコ
ーティングする等、患者が服用しやすいように工夫する
必要があった。2. Description of the Related Art Pravastatin sodium rapidly and powerfully lowers serum cholesterol levels and improves serum lipids by specifically and antagonistically inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Is a therapeutic agent for hyperlipidemia and familial hypercholesterolemia, which is widely used clinically worldwide. Pravastatin sodium is a white to slightly off-white powder or a crystalline powder having a bitter taste. For this reason, it is necessary to devise preparations to be used for treatment, such as fine granules and tablets, by coating them with a polymer substance so that the patient can easily take them.
【０００３】[0003]
【発明が解決しようとする課題】プラバスタチンナトリ
ウムは、比較的不安定な化合物であり、種々の製剤化助
剤と反応するため、良好な安定性を確保するためにいろ
いろな工夫が行われている。例えば、特許第２９３５２
２０号公報にはプラバスタチン及び水に分散したときの
ｐＨが９以上となる塩基性化剤からなる安定性良好な医
薬組成物が開示されている。しかし、さらなる安定化技
術及び苦味を防止できる技術が求められており、本発明
者はこれら課題を解決するため鋭意検討した結果、全く
意外なことに以下に示す構成により、課題を解決できる
ことを見い出し本発明を完成した。Pravastatin sodium is a relatively unstable compound, and reacts with various formulation auxiliaries, so that various efforts have been made to ensure good stability. . For example, Japanese Patent No. 29352
No. 20 discloses a stable pharmaceutical composition comprising pravastatin and a basifying agent having a pH of 9 or more when dispersed in water. However, further stabilization technology and technology capable of preventing bitterness are required, and as a result of intensive studies to solve these problems, the present inventor has found that, surprisingly, the following structure can solve the problems. The present invention has been completed.
【０００４】[0004]
【課題を解決するための手段】本発明は、プラバスタチ
ンナトリウム、糖類及び結合剤からなるプラバスタチン
ナトリウム含有組成物である。また、本発明は、プラバ
スタチンナトリウム、糖類、結合剤及びl-メントールか
らなるプラバスタチンナトリウム含有組成物である。更
に、本発明はプラバスタチンナトリウム及び糖類を混合
し、結合剤を溶解した水及び／又は水溶解性有機溶媒を
加えて練合し、フィルムを介して圧縮成形する錠剤の製
造方法である。本発明により製造した錠剤は、第１３改
正日本薬局方崩壊試験法による崩壊試験を行うとき、
０．０５〜３分で崩壊する。SUMMARY OF THE INVENTION The present invention is a pravastatin sodium-containing composition comprising pravastatin sodium, a saccharide and a binder. The present invention is also a pravastatin sodium-containing composition comprising pravastatin sodium, a saccharide, a binder and l-menthol. Further, the present invention is a method for producing a tablet, which comprises mixing pravastatin sodium and a saccharide, adding water and / or a water-soluble organic solvent in which a binder is dissolved, kneading the mixture, and compression-molding through a film. Tablets manufactured according to the present invention, when performing a disintegration test according to the thirteenth revised Japanese Pharmacopoeia disintegration test method,
Disintegrates in 0.05-3 minutes.
【０００５】プラバスタチンナトリウムは、化学名sodi
um(+)-(3R,5R)-3,5-dihydroxy-7-[(1S,2S,6S,8S,8aR)-6
-hydroxy-2-methyl-8-[(S)-2-methylbutyryloxy]-1,2,
6,7,8,8a-hexahydro-1-naphthyl]heptanoateであり、コ
レステロール生合成系の律速酵素であるHMG-CoA還元酵
素を特異的・拮抗的に阻害することによる高脂血症、家
族性高コレステロール治療剤である。プラバスタチンナ
トリウムは、従来公知の方法により製造することができ
る。Pravastatin sodium has the chemical name sodi
um (+)-(3R, 5R) -3,5-dihydroxy-7-[(1S, 2S, 6S, 8S, 8aR) -6
-hydroxy-2-methyl-8-[(S) -2-methylbutyryloxy] -1,2,
6,7,8,8a-hexahydro-1-naphthyl] heptanoate, a hyperlipidemia and familial disease caused by the specific and antagonistic inhibition of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis It is a high cholesterol therapeutic agent. Pravastatin sodium can be produced by a conventionally known method.
【０００６】本発明における糖類とは、乳糖及びマンニ
トールである。乳糖及びマンニトールは単独で使用して
も両者を同時に使用してもよい。また、本発明における
結合剤は、ポリビニルピロリドン、ポリビニルアルコー
ル、ヒドロキシプロピルメチルセルロース及びヒドロキ
シプロピルセルロースから選ばれる結合剤であり、これ
らを単独で使用しても２種以上を組合わせて使用しても
よい。本発明において、プラバスタチンナトリウムと糖
類及び結合剤の配合量は特に限定されないが、通常プラ
バスタチンナトリウム１重量部に対し、糖類９〜４９重
量部及び結合剤０．０５〜５重量部であり、好ましく
は、プラバスタチンナトリウム１重量部に対し、糖類１
０〜４０重量部及び結合剤０．１〜５重量部である。[0006] The saccharides in the present invention are lactose and mannitol. Lactose and mannitol may be used alone or both at the same time. Further, the binder in the present invention is a binder selected from polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropylmethylcellulose and hydroxypropylcellulose, and these may be used alone or in combination of two or more. . In the present invention, the amounts of pravastatin sodium, the saccharide and the binder are not particularly limited, but are usually 9 to 49 parts by weight of the saccharide and 0.05 to 5 parts by weight of the binder with respect to 1 part by weight of pravastatin sodium. , 1 part by weight of pravastatin sodium and 1 part of saccharide
0 to 40 parts by weight and 0.1 to 5 parts by weight of binder.
【０００７】本発明においては、更にl-メントールを混
合することができる。これにより、糖類による甘味に加
え爽快感を付与することができ、服用した際のプラバス
タチンナトリウムの苦味を軽減することができる。l-メ
ントールの配合量は、製剤全量に対して０．０１〜０．
５重量％、好ましくは０．０２〜０．３重量％である。
更に、甘味成分としてステビアを添加するとプラバスタ
チンの苦味をより軽減することができる。[0007] In the present invention, l-menthol can be further mixed. Thereby, in addition to the sweetness of the saccharide, a refreshing feeling can be imparted, and the bitterness of pravastatin sodium when taken can be reduced. The blending amount of l-menthol is 0.01 to 0.
It is 5% by weight, preferably 0.02 to 0.3% by weight.
Further, the addition of stevia as a sweet component can further reduce the bitterness of pravastatin.
【０００８】本発明にかかる組成物は、必要に応じて製
剤化助剤を加えて顆粒剤、細粒剤とすることができ、更
にカプセルに充填してカプセル剤とすることもでき、あ
るいは打錠して錠剤とすることもできる。プラバスタチ
ンは不安定な薬物であるので、添加する製剤化助剤は全
量の１０％までとすることが好ましい。更に、本願組成
物は、エタノール等の水溶性有機溶媒及び／又は水を加
えて練合し、モールド錠とするのに適している。練合時
には結合剤をあらかじめ水溶性有機溶媒及び／又は水に
溶解したものを添加して練合することもできる。モール
ド錠は、口腔内で速やかに崩壊するため老人にも服用し
やすい剤形であり、例えば特開平８―１９５８９号公報
に開示される装置によると生産スケールで製造すること
ができる。本発明におけるモールド錠の第１３改正日本
薬局方崩壊試験法による崩壊時間は、０．０５〜３分で
ある。[0008] The composition according to the present invention can be made into granules and fine granules by adding a formulation aid as necessary, and can be filled into capsules to form capsules or Tablets can also be made into tablets. Since pravastatin is an unstable drug, it is preferable to add up to 10% of the formulation aid to be added. Furthermore, the composition of the present invention is suitable for kneading by adding a water-soluble organic solvent such as ethanol and / or water to form a molded tablet. At the time of kneading, kneading can also be carried out by adding a binder dissolved in a water-soluble organic solvent and / or water in advance. A molded tablet is a dosage form that disintegrates quickly in the oral cavity and is easily taken by elderly people. For example, according to the device disclosed in JP-A-8-19589, it can be manufactured on a production scale. The disintegration time of the molded tablet according to the thirteenth revised Japanese Pharmacopoeia disintegration test method of the present invention is 0.05 to 3 minutes.
【０００９】[0009]
【効果】本発明にかかる組成物は、プラバスタチンナト
リウムの安定性が良好で、更に苦味を軽減した服用しや
すいものである。以下に本発明にかかる組成物の優れた
効果を詳細に説明する。 試験例１ プラバスタチン１ｇに製剤化助剤１０ｇを加え乳鉢で混
合後、その約１ｇをバイアル瓶に入れ４０℃湿度７５％
の条件下で１週間開放保存した。結果を表１に示した。The composition according to the present invention has good stability of pravastatin sodium and is easy to take with reduced bitterness. Hereinafter, the excellent effects of the composition according to the present invention will be described in detail. Test Example 1 10 g of a formulation aid was added to 1 g of pravastatin, mixed in a mortar, and about 1 g was placed in a vial, and the humidity at 40 ° C was 75%.
Was stored openly for one week under the conditions described above. The results are shown in Table 1.
【表１】 表１よりプラバスタチンは多くの製剤化助剤と相互作用
を起こすことが明らかである。[Table 1] It is clear from Table 1 that pravastatin interacts with many formulation aids.
【００１０】試験例２ 実施例１〜３で得られた錠剤を、ＰＴＰ包装、ＰＴＰ／
アルミ包装又は開放条件下で、冷所、２５℃湿度７５
％、４０℃湿度７５％、４５℃、６０℃及び１０００lu
xで１ヶ月間保存したときのプラバスタチンの残存量及
び分解物量を高速液体クロマトグラフィーにより測定し
た。対照として市販のプラバスタチン錠を用いた。結果
を表２に示した。Test Example 2 The tablets obtained in Examples 1 to 3 were packed in a PTP package,
Aluminum package or open condition, cool place, 25 ℃, humidity 75
%, 40 ° C, 75% humidity, 45 ° C, 60 ° C and 1000lu
The amount of pravastatin remaining and the amount of degraded product after storage for 1 month at x were measured by high performance liquid chromatography. As a control, a commercially available pravastatin tablet was used. The results are shown in Table 2.
【表２】 表２より、４０℃湿度７５％、４５℃及び６０℃の条件
下では市販のプラバスタチン錠は分解物量が増大し、４
５℃及び６０℃の条件下では残存量も減少したが、本願
発明にかかる組成物は安定であることが明らかである。[Table 2] From Table 2, it can be seen that under the conditions of 40 ° C., 75% humidity, 45 ° C. and 60 ° C., the amount of degraded product of the commercially available pravastatin tablet increases,
Although the residual amount also decreased under the conditions of 5 ° C. and 60 ° C., it is clear that the composition according to the present invention is stable.
【００１１】[0011]
【実施例】実施例１ プラバスタチン１００ｇ及びＤ−マンニトール１８９０
ｇを混合し、更にポリビニルアルコール１０ｇを溶解し
たエタノール・水混合溶媒を２４０ｍｌ添加し練合し
た。この練合物を特開平８―１９５８９号公報で開示さ
れる装置を用いて製錠し、乾燥して１錠約２００ｍｇの
錠剤を得た。この錠剤の第１３改正日本薬局方崩壊試験
法による崩壊時間は、１４．２秒（６錠の平均）であっ
た。 実施例２ プラバスタチン１００ｇ及びＤ−マンニトール１８８０
ｇを混合し、更にポリビニルピロリドン２０ｇを溶解し
たエタノール・水混合溶媒を２４０ｍｌ添加し練合し
た。この練合物を特開平８―１９５８９号公報で開示さ
れる装置を用いて製錠し、乾燥して１錠約２００ｍｇの
錠剤を得た。この錠剤の第１３改正日本薬局方崩壊試験
法による崩壊時間は、１４．７秒（６錠の平均）であっ
た。EXAMPLES Example 1 Pravastatin 100 g and D-mannitol 1890
g of the mixture, and 240 ml of a mixed solvent of ethanol and water in which 10 g of polyvinyl alcohol was dissolved was added and kneaded. The kneaded product was tableted using an apparatus disclosed in JP-A-8-19589, and dried to obtain a tablet of about 200 mg per tablet. The disintegration time of this tablet according to the 13th Revised Japanese Pharmacopoeia Disintegration Test Method was 14.2 seconds (average of 6 tablets). Example 2 Pravastatin 100 g and D-mannitol 1880
g of the mixture, and 240 ml of a mixed solvent of ethanol and water in which 20 g of polyvinylpyrrolidone was dissolved was added and kneaded. The kneaded product was tableted using an apparatus disclosed in JP-A-8-19589, and dried to obtain a tablet of about 200 mg per tablet. The disintegration time of this tablet according to the 13th Revised Japanese Pharmacopoeia Disintegration Test Method was 14.7 seconds (average of 6 tablets).
【００１２】実施例３ プラバスタチン５０ｇ及びＤ−マンニトール１５４０ｇ
を混合し、更にポリビニルアルコール８ｇを溶解したエ
タノール・水混合溶媒を１９２ｍｌ添加し練合した。こ
の練合物を特開平８―１９５８９号公報で開示される装
置を用いて製錠し、乾燥して１錠約１６０ｍｇの錠剤を
得た。この錠剤の第１３改正日本薬局方崩壊試験法によ
る崩壊時間は、５．８秒（６錠の平均）であった。 実施例４ プラバスタチン５０ｇ、Ｄ−マンニトール１０００ｇ及
び乳糖５４０ｇを混合し、更にポリビニルアルコール８
ｇを溶解したエタノール・水混合溶媒を２００ｍｌ添加
し練合した。この練合物を押出し造粒機により造粒後、
乾燥し顆粒剤を得た。 実施例５ プラバスタチン１ｇ及びＤ−マンニトール１８.７ｇを
混合し、別にポリビニルアルコール２ｇ、ステビア４ｇ
及び ｌ―メントール０．３６ｇをエタノール・水混合
溶媒３２ｍｌに溶解し、そのを１.９ｍｌを添加し練合
した。この練合物をオートグラフにより圧縮成形し、乾
燥して１錠約１００ｍｇの錠剤を得た。この錠剤を服用
したところ、苦味はほとんど気にならなかった。Example 3 50 g of pravastatin and 1540 g of D-mannitol
And 192 ml of an ethanol / water mixed solvent in which 8 g of polyvinyl alcohol was dissolved was added and kneaded. The kneaded product was tableted using an apparatus disclosed in JP-A-8-19589, and dried to obtain a tablet of about 160 mg per tablet. The disintegration time of this tablet according to the 13th Revised Japanese Pharmacopoeia Disintegration Test Method was 5.8 seconds (average of 6 tablets). Example 4 50 g of pravastatin, 1000 g of D-mannitol and 540 g of lactose were mixed, and polyvinyl alcohol 8
Then, 200 ml of an ethanol / water mixed solvent in which g was dissolved was added and kneaded. After extruding this kneaded product with an extrusion granulator,
It was dried to obtain granules. Example 5 1 g of pravastatin and 18.7 g of D-mannitol were mixed, and 2 g of polyvinyl alcohol and 4 g of stevia were separately added.
And 0.36 g of l-menthol were dissolved in 32 ml of a mixed solvent of ethanol and water, and 1.9 ml of the solution was added and kneaded. The kneaded product was compression-molded by an autograph and dried to obtain a tablet of about 100 mg per tablet. The bitter taste was hardly noticed when the tablet was taken.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｐ 43/00 １０１ Ａ６１Ｐ 43/00 １０１ Ｆターム(参考） 4C076 AA30 AA31 AA36 AA53 BB04 CC14 DD34T DD41C DD66A DD67A EE16B EE31A EE33A EE33B FF04 FF05 FF06 FF09 FF52 4C206 DB11 MA03 MA05 MA72 ZC20 ZC33 ──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 7 Identification symbol FI theme coat ゛ (reference) A61P 43/00 101 A61P 43/00 101 F term (reference) 4C076 AA30 AA31 AA36 AA53 BB04 CC14 DD34T DD41C DD66A DD67A EE16B EE31A EE33A EE33B FF04 FF05 FF06 FF09 FF52 4C206 DB11 MA03 MA05 MA72 ZC20 ZC33
Claims (7)
剤からなるプラバスタチンナトリウム含有組成物。1. A pravastatin sodium-containing composition comprising pravastatin sodium, a saccharide and a binder.
る請求項１記載の組成物。2. The composition according to claim 1, wherein the saccharide is lactose and / or mannitol.
ニルアルコール、ヒドロキシプロピルメチルセルロース
及びヒドロキシプロピルセルロースから選ばれる１種以
上の結合剤である請求項１記載の組成物。3. The composition according to claim 1, wherein the binder is at least one binder selected from polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropylmethylcellulose and hydroxypropylcellulose.
し、糖類９〜４９重量部及び結合剤０．０５〜５重量部
を含有する請求項１記載の組成物。4. The composition according to claim 1, comprising 9 to 49 parts by weight of a saccharide and 0.05 to 5 parts by weight of a binder per 1 part by weight of pravastatin sodium.
及びl-メントールからなるプラバスタチンナトリウム含
有組成物。5. A pravastatin sodium-containing composition comprising pravastatin sodium, a saccharide, a binder and l-menthol.
し、結合剤を溶解した水及び／又は水溶解性有機溶媒を
加えて練合し、充填穴に充填後フィルムを介して圧縮成
形する錠剤の製造方法。6. A method for producing a tablet, comprising mixing pravastatin sodium and a saccharide, kneading by adding water and / or a water-soluble organic solvent in which a binder has been dissolved, filling in a filling hole, and compression-molding through a film. .
し、結合剤を溶解した水及び／又は水溶解性有機溶媒を
加えて練合し、充填穴に充填後フィルムを介して圧縮成
形する第１３改正日本薬局方崩壊試験法による崩壊時間
が０．０５分から３分である錠剤の製造方法。7. A thirteenth revised Japan wherein pravastatin sodium and a saccharide are mixed, kneaded by adding water and / or a water-soluble organic solvent in which a binder is dissolved, and filling in a filling hole, followed by compression molding through a film. A method for producing a tablet having a disintegration time of 0.05 to 3 minutes by a pharmacopeia disintegration test method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000196313A JP4138209B2 (en) | 2000-06-29 | 2000-06-29 | Pravastatin-containing composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000196313A JP4138209B2 (en) | 2000-06-29 | 2000-06-29 | Pravastatin-containing composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002020282A true JP2002020282A (en) | 2002-01-23 |
| JP4138209B2 JP4138209B2 (en) | 2008-08-27 |
Family
ID=18694832
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000196313A Expired - Fee Related JP4138209B2 (en) | 2000-06-29 | 2000-06-29 | Pravastatin-containing composition |
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| Country | Link |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BG934U1 (en) * | 2006-12-14 | 2007-11-30 | "Софарма" Ад | Composition for solid medicinal form containing pravastatin |
| JP2010053043A (en) * | 2008-08-26 | 2010-03-11 | Takada Seiyaku Kk | Tablet quickly disintegrating in oral cavity |
| EP1731147A4 (en) * | 2004-03-31 | 2010-06-30 | Kowa Co | EXTERNAL PREPARATION |
| JP2010533210A (en) * | 2007-07-13 | 2010-10-21 | ジェネリクス・（ユーケー）・リミテッド | Stable pharmaceutical composition comprising one or more HMG-CoA reductase inhibitors |
| US8685731B2 (en) | 2006-07-14 | 2014-04-01 | Dsm Ip Assets B.V. | Process for the culturing of cells |
| US9260695B2 (en) | 2004-03-05 | 2016-02-16 | Dpx Holdings B.V. | Process for cell culturing by continuous perfusion |
-
2000
- 2000-06-29 JP JP2000196313A patent/JP4138209B2/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9260695B2 (en) | 2004-03-05 | 2016-02-16 | Dpx Holdings B.V. | Process for cell culturing by continuous perfusion |
| EP1731147A4 (en) * | 2004-03-31 | 2010-06-30 | Kowa Co | EXTERNAL PREPARATION |
| US8685731B2 (en) | 2006-07-14 | 2014-04-01 | Dsm Ip Assets B.V. | Process for the culturing of cells |
| US9469865B2 (en) | 2006-07-14 | 2016-10-18 | Dpx Holdings B.V. | Process for the culturing of cells |
| US9670520B2 (en) | 2006-07-14 | 2017-06-06 | Patheon Holdings | B.V. | Process for the culturing of cells |
| BG934U1 (en) * | 2006-12-14 | 2007-11-30 | "Софарма" Ад | Composition for solid medicinal form containing pravastatin |
| JP2010533210A (en) * | 2007-07-13 | 2010-10-21 | ジェネリクス・（ユーケー）・リミテッド | Stable pharmaceutical composition comprising one or more HMG-CoA reductase inhibitors |
| JP2010053043A (en) * | 2008-08-26 | 2010-03-11 | Takada Seiyaku Kk | Tablet quickly disintegrating in oral cavity |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4138209B2 (en) | 2008-08-27 |
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