JPH03206039A - Nifedipin preparation having prolonged action - Google Patents
Nifedipin preparation having prolonged actionInfo
- Publication number
- JPH03206039A JPH03206039A JP205690A JP205690A JPH03206039A JP H03206039 A JPH03206039 A JP H03206039A JP 205690 A JP205690 A JP 205690A JP 205690 A JP205690 A JP 205690A JP H03206039 A JPH03206039 A JP H03206039A
- Authority
- JP
- Japan
- Prior art keywords
- nifedipine
- weight
- hpmc
- parts
- preparation
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 230000002035 prolonged effect Effects 0.000 title abstract 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 47
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 47
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 14
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 14
- 239000001856 Ethyl cellulose Substances 0.000 claims abstract description 8
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims abstract description 8
- 235000019325 ethyl cellulose Nutrition 0.000 claims abstract description 8
- 229920001249 ethyl cellulose Polymers 0.000 claims abstract description 8
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract 7
- 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 abstract 7
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract 4
- 229960001597 nifedipine Drugs 0.000 claims description 72
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 claims description 71
- 239000008280 blood Substances 0.000 abstract description 8
- 210000004369 blood Anatomy 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 5
- 238000013329 compounding Methods 0.000 abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- 239000000843 powder Substances 0.000 description 15
- 238000009472 formulation Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000002250 absorbent Substances 0.000 description 3
- 230000002745 absorbent Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000003405 delayed action preparation Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- 229920002675 Polyoxyl Polymers 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 229960003368 croscarmellose sodium type a Drugs 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- -1 etc.) Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102100032273 DNA-directed RNA polymerase III subunit RPC6 Human genes 0.000 description 1
- 102100039852 DNA-directed RNA polymerases I and III subunit RPAC2 Human genes 0.000 description 1
- 101100038189 Dictyostelium discoideum rpc9 gene Proteins 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 101001088194 Homo sapiens DNA-directed RNA polymerase III subunit RPC6 Proteins 0.000 description 1
- 101000669171 Homo sapiens DNA-directed RNA polymerases I and III subunit RPAC2 Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 101100091513 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) RPB5 gene Proteins 0.000 description 1
- 101000686027 Schizosaccharomyces pombe (strain 972 / ATCC 24843) DNA-directed RNA polymerases I, II, and III subunit RPABC2 Proteins 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 208000032764 hereditary 10 prostate cancer Diseases 0.000 description 1
- 229960001545 hydrotalcite Drugs 0.000 description 1
- 229910001701 hydrotalcite Inorganic materials 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000036513 peripheral conductance Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、簡単、かつ効率的に製造することができる、
速効性かつ持続性を有するニフェジピン持続性製剤に関
する．
〔従来の技術・発明が解決しようとする課題〕ニフェジ
ピンは優れた冠血管拡張作用、末梢血管抵抗の減少など
の作用を有し、狭心症、高血圧症の治療剤として使用さ
れている．その作用機序はカルシウムイオンの細胞内流
入を阻害するカルシウム拮抗作用に基づくことが知られ
ている。[Detailed description of the invention] [Industrial application field] The present invention can be easily and efficiently manufactured.
This article relates to a nifedipine long-acting formulation that is fast-acting and long-lasting. [Prior Art/Problems to be Solved by the Invention] Nifedipine has excellent coronary vasodilatory effects and reduces peripheral vascular resistance, and is used as a therapeutic agent for angina pectoris and hypertension. Its mechanism of action is known to be based on calcium antagonism, which inhibits the influx of calcium ions into cells.
狭心症は、緊急を要する疾患であり、発作時にはニフェ
ジピンの血中濃度を急激に高めることが求められるため
、迅速で確実な効果を発現する製剤であることが要求さ
れる．さらに、薬剤の投与回数を減らし、服薬コンブラ
イアンスを高めるた１１４
めにニフェジピン持続性製剤であることが要求されてい
る．
持続性製剤としては、ニフェジピン速放部と遅放部から
なる製剤（特開昭５８−４６０１９号公報、特開昭６１
−８号公報など）、微粉化したニフェジピンを含有する
製剤（特開昭５７−５０９１３号公報など）などが提案
されている．
しかし、これらの製剤は、ニフエジビン速放部と遅放部
を別々に製造する工程を経て製造される、ニフェジピン
を微粉化する工程が必要であるなどの製造工程が多くな
るという問題点がある．従って本願発明は、従来の持続
性製剤より極めて簡単に製造することができ、かつ優れ
た速効性と持続性を有するニフェジピン持続性製剤を提
供することを目的とする．
〔課題を解決するための手段〕
本願発明者は、上記目的を達成するために種々研究を重
ねてきたところ、ニフェジピン、エチルセルロース（以
下、ＥＣと略記する）とヒドロキシブロピルメチルセル
ロース（以下、ＨＰＭＣと略記する）よりなり、ニフェ
ジピン１００重量部に対してＥＣとＨＰＭＣとの和が１
００〜３００重量部であり、かつ、ＥＣＩＯＯ重量部に
対してＨＰＭＣが４００〜９００重量部の割合で配合さ
れたニフェジピン製剤が、並びにニフェジピン、ＥＣ，
ＨＰＭＣおよびヒドロキシプロビルセルロース（以下、
ＲＰＣと略記する）よりなり、ニフェジピン１００重量
部に対してＥＣ，ＨＰＭＣおよびＨＰＣとの和が１００
〜３００重量部であり、かつＥＣＩＯＯ重量部に対して
ＨＰＭＣとＨＰＣとの和が４００〜９００重量部の割合
で配合されたニフェジピン製剤が、ニフェジピンの作用
の速効性と持続時間の延長が図られ、かつ極めて簡単、
効率的に製造できることを見出して本発明を完威した．
即ち、本発明の要旨は次の通りである．（１）ニフェジ
ピン、ＥＣおよびＨＰＭＣよりなり、ニフェジピン１０
０重量部に対してＥＣとＨ ＰＭＣとが、その総量とし
て１００〜３００重量部の割合で配合され、かつ、ＥＣ
ＩＯＯ重量部に対してＨＰＭＣが４００〜９００重量部
の割合で配合されてなることを特徴とするニフェジピン
持続性製剤．
（２）ニフェジピン、ＥＣ，ＨＰＭＣおよびＨＰＣが配
合されてなり、ニフエジビン１００重量部に対してＥＣ
とＨＰＭＣとＲＰＣとが、その総量として１００〜３０
０重量部の割合で配合され、かつ、ＥＣＩＯＯ重量部に
対してＨＰＭＣとＲＰＣとが、その総量として４００〜
９００重量部の割合で配合されてなることを特徴とする
ニフェジピン持続性製剤．
本発明において、ニフェジピンに対するＥＣとＨＰＭＣ
との和またはＥＣとＨＰＭＣとＩ｛ＰＣとの和の割合は
、ニフェジピン１００重量部に対してＥＣとＨＰＭＣと
の和（さらに、ＲＰＣが配合される場合には、それをも
加えた和）が１００〜３００重量部、好ましくは１１０
〜１８０重量部、さらに好ましくは１３０〜１６０重量
部、そして最も好ましくは１５０重量部程度である．し
かして、ＥＣとＨＰＭＣ （さらに、ＲＰＣが配合され
る場合には、それをも加えた和）との和が１００重量部
より少ない場合、ニフェジピンの溶出性が悪くなる．ま
た、３００重量部を越える場合には、ニフェジピンの溶
出性は良くなるが、例えば錠剤にした場合、錠剤が大き
くなり服用しにくくなる。Angina pectoris is a disease that requires an emergency, and it is necessary to rapidly increase the blood concentration of nifedipine in the event of an attack, so a drug that exhibits rapid and reliable effects is required. Furthermore, a long-acting formulation of nifedipine is required to reduce the number of drug administrations and increase compliance. As long-acting preparations, preparations consisting of an immediate release part and a slow release part of nifedipine (JP-A-58-46019, JP-A-61
-8, etc.), and formulations containing micronized nifedipine (Japanese Patent Application Laid-Open No. 57-50913, etc.). However, these formulations have problems in that they require a large number of manufacturing steps, such as the process of separately manufacturing the immediate-release part and slow-release part of nifedipine, and the need for a step to pulverize nifedipine. Therefore, an object of the present invention is to provide a long-acting preparation of nifedipine that can be produced much more easily than conventional long-acting preparations and has excellent rapid action and durability. [Means for Solving the Problems] In order to achieve the above object, the inventor of the present application has conducted various studies and discovered that nifedipine, ethylcellulose (hereinafter abbreviated as EC) and hydroxybropyl methylcellulose (hereinafter referred to as HPMC) ), and the sum of EC and HPMC is 1 for 100 parts by weight of nifedipine.
00 to 300 parts by weight, and a nifedipine preparation containing 400 to 900 parts by weight of HPMC to parts by weight of ECIOO, as well as nifedipine, EC,
HPMC and hydroxyprobyl cellulose (hereinafter referred to as
(abbreviated as RPC), and the sum of EC, HPMC, and HPC is 100 parts by weight per 100 parts by weight of nifedipine.
-300 parts by weight, and a nifedipine formulation containing 400 to 900 parts by weight of HPMC and HPC relative to parts by weight of ECIOO is designed to achieve rapid action and prolong the duration of the action of nifedipine. , and extremely easy,
The present invention was perfected by discovering that it can be manufactured efficiently. That is, the gist of the present invention is as follows. (1) Consisting of nifedipine, EC and HPMC, nifedipine 10
EC and HPMC are blended in a total amount of 100 to 300 parts by weight to 0 parts by weight, and
A long-acting preparation of nifedipine, characterized in that HPMC is blended in a ratio of 400 to 900 parts by weight to parts by weight of IOO. (2) Nifedipine, EC, HPMC and HPC are combined, and EC
, HPMC, and RPC, the total amount is 100 to 30
HPMC and RPC are blended in a ratio of 0 parts by weight, and the total amount of HPMC and RPC is 400 to 400 parts by weight with respect to ECIOOO parts by weight.
A long-acting preparation of nifedipine, characterized in that it is formulated in a proportion of 900 parts by weight. In the present invention, EC and HPMC for nifedipine
The ratio of the sum of EC, HPMC, and I{PC is the sum of EC and HPMC (and also the sum of RPC if it is blended) to 100 parts by weight of nifedipine. is 100 to 300 parts by weight, preferably 110 parts by weight.
The amount is about 180 parts by weight, more preferably 130 to 160 parts by weight, and most preferably about 150 parts by weight. However, if the sum of EC and HPMC (and RPC, if included) is less than 100 parts by weight, the dissolution of nifedipine will deteriorate. If the amount exceeds 300 parts by weight, the dissolution of nifedipine is improved, but when it is made into tablets, for example, the tablets become large and difficult to take.
従って、上記の割合であれば、ニフェジピンの溶出性が
良く、ニフェジピンの持続性製剤、即ち徐放性製剤とし
ての溶出パターンも良く、錠剤などの製剤がコンパクト
化できる．
次に、ＥＣに対するＨＰＭＣ，またはＨＰＭＣとＲＰＣ
との和の割合は、ＥＣＩＯＯ重量部に対してＨＰＭＣ，
または、ＨＰＭＣとＲＰＣとの和が４００〜９００重量
部、好ましくは、５００〜６００重量部、さらに好まし
くは５５０重量部程度である．しかしてＨＰＭＣ、また
はＨＰＭＣとＨＰＣとの和が４００重量部より少ない場
合、ニフェジピンの溶出が遅くなり血中濃度が上がらな
い．また、９００重量部を越える場合には、ニフェジピ
ンの溶出が早くなり、徐放効果がなくなる．従って、上
記の割合であれば、良好な持続性製剤、即ち徐放性製剤
を提供することができる．本発明における各威分の、特
に好ましい配合割合は、ニフェジピン１００重量部に対
して、ＥＣが１５〜３０重量部、ＨＰＭＣ （さらに、
ＲＰＣを配合する場合にはそれをも加えた和）が１２０
〜１３５重量部の範囲である．また、ＨＰＭＣに加えて
ＨＰＣを配合する場合、ＨＰＭＣに対するＲＰＣの配合
割合は、ＨＰＭＣＩ ００重量部に対して１０−１００
重量部、好ましくは４０〜７０重量部、さらに好ましく
は５５重量部程度である．本発明の製剤には必要により
、熔解促進剤（例えば、ステアリン酸ポリオキシル４０
，ポリソルベート８０、ラウリル硫酸ナトリウムなど）
、賦形剤（例えば、メタケイ酸アルミン酸マグネシウム
、部分アルファ一化デンプン、結晶セルロース、乳糖、
含水二酸化ケイ素、ヒドロキシプロビルスターチなど）
、滑沢剤（例えば、ステアリン酸マグネシウム、タルク
、硬化油など〉、崩壊剤（例えば、クロスカルメロース
ナトリウムＡ型、カルボキシメチルセルロースなど）な
どを添加することができる．
本発明の製剤は、液体をよく吸着する粉末、たとえば当
該粉末１ｇが液体２ｄ以上、好ましくは２．５ｍｌ以上
を吸着するもの（通常、２〜４ｍ，好ましくは、Ｚ５〜
３．５ｄ，特に、２．．７〜＆４−の液体を吸着するも
の）（以下、高吸着性粉末ともいう）を、通常、１５〜
４０重量％、好ましくは、２０〜３０重量％、特に好ま
しくは、２５重置％程度含む粉末混合物に、ニフェジピ
ン、ＥＣおよびＨＰＭＣ （さらに所望によりＲＰＣ）
よりなる層を被覆してなるか、または粉末混合物にニフ
ェジピン、ＥＣおよびＨＰＭＣ （さらに所望によりＨ
ＰＣ）を吸着させてなる製剤よりなるものであることが
好都合である．
当該高吸着性粉末の粒子径は、通常、４０〜２００μｍ
、好ましくは、４５〜１７５μｍであり、また多孔性粉
末であることが好適である．高吸着性粉末の具体例とし
ては、例えばメタケイ酸アルξン酸マグネシウム、軽質
無水ケイ酸、合威ヒドロタルサイトなどが例示される．
上記高吸着性粉末に加えて配合される粉末としては、例
えばその粒子径が１５０〜５００μｍ，特に２５０〜３
５５μｍのものが好適であり、かかる粉末としては、例
えば結晶セルロース、部分アルファ−化デンプン、乳糖
、含水二酸化ケイ素、ヒドロキシブロピルスターチなど
が例示される．ニフェジピン、ＥＣおよびＨＰＭＣ （
さらに所望によりＲＰＣ）の総量１００重量部に対して
、上記粉末混合物は通常、５０〜８００重量部、好適に
は１５０〜２５０重量部配合される．本発明の製剤は、
例えば次の様にして製造される．即ち、ニフェジピンを
適当な溶媒（例えば、エタノール、塩化メチレン、エタ
ノール・塩化メチレン混液、アセトン、アセトン・エタ
ノール混液なと）に溶解させてニフェジピン溶液を調製
する．その際、溶解補助剤（例えば、ステアリン酸ボリ
オキシル４０、ポリソルベート８０、ポリオキシエチレ
ンステアレート、ラウリル硫酸ナトリウムなど）を使用
することが好ましい．一方、ＥＣおよびＨＰＭＣまたは
ＥＣ，ＨＰＭＣおよびＨＰＣを上記と同様の溶媒に溶解
させて高分子化合物混合溶液を調製する．このニフェジ
ピン溶液と高分子化合物混合溶液とを均一に混合し、こ
れを、例えばメタケイ酸アル壽ン酸マグネシウム、結晶
セルロース、部分アルファ−化デンブン、乳糖などの混
合末に噴霧して、コーティングすることによって、ニフ
ェジピン被覆（吸着）組戒物を調製する．
当該組威物は常法によって錠剤、顆粒剤、カプセル剤、
散剤などに製剤化することができる．特に本願発明の製
剤は、顆粒剤、カプセル剤、散剤などの態様とすること
は勿論のこと、上記ニフェジピン被覆（吸着）組底物は
打錠が容易であることから、極めて容易に錠剤化するこ
とができる．
本発明の製剤は、通常経口的に投与される．その投与量
はニフェジピンとして、１日２０〜４０■程度であり、
１日１〜２回の投与で十分その薬効が発揮される．
〔作用・効果］
本発明のニフェジピン持続性製剤はその製造が極めて簡
単、かつ効率的である．しかも、本発明のニフェジピン
持続性製剤によれば、ニフエジビンの溶出をコントロー
ルしたマトリソクスから、速やかにニフヱジピンが有効
血中濃度にまで吸収され、血中濃度を長時間、治療濃度
域に維持し作用の持続化をはかることができる．しかし
て、本発明の製剤を使用すれば、その投与回数が少なく
なるので、服用に便利であり服薬コンブライアンスを高
めることができ、投与のたびに起こる血中濃度の変動が
少なくなるので薬効発現が安定するという効果を有する
．
〔実施例〕
以下に実施例および比較例を示して、本発明によるニフ
エジビン持続性製剤を説明するが、本発明はこれら実施
例により何ら限定されるものではない．
なお、以下の記載において、ニフェジピン溶液とは、ニ
フェジピン（２０■）をステアリン酸ボリオキシル４０
（４■）とともにエタノール・塩化メチレン（重量比６
：４）混液１２０ｄに溶解したものをいう．
実施例１
ＥＣ３■、ＨＰＭＣ１８■、ＨＰＣ９■（ニフェジピン
重量に対して０．１５：０．９：０．４５）をエタノー
ル・塩化メチレン（重量比６：４）混液３００ｄに溶解
し、この溶液とニフェジピン溶液を均一に混合した。Therefore, at the above ratio, the dissolution of nifedipine is good, the dissolution pattern of nifedipine as a long-acting preparation, that is, a sustained release preparation is good, and the preparation such as a tablet can be made compact. Next, HPMC for EC, or HPMC and RPC
The ratio of the sum of HPMC,
Alternatively, the sum of HPMC and RPC is about 400 to 900 parts by weight, preferably about 500 to 600 parts by weight, and more preferably about 550 parts by weight. However, if the HPMC or the sum of HPMC and HPC is less than 400 parts by weight, the elution of nifedipine will be delayed and the blood concentration will not increase. Furthermore, if the amount exceeds 900 parts by weight, the elution of nifedipine becomes rapid and the sustained release effect is lost. Therefore, with the above ratio, it is possible to provide a good sustained-release preparation, that is, a sustained-release preparation. A particularly preferable blending ratio of each ingredient in the present invention is 15 to 30 parts by weight of EC and 15 to 30 parts by weight of HPMC (furthermore,
If RPC is included, the sum including that is 120
~135 parts by weight. In addition, when blending HPC in addition to HPMC, the blending ratio of RPC to HPMC is 10-100 parts by weight per 00 parts by weight of HPMCI.
The amount is preferably about 40 to 70 parts by weight, more preferably about 55 parts by weight. The formulation of the present invention may optionally contain a solubility accelerator (for example, polyoxyl stearate 40
, polysorbate 80, sodium lauryl sulfate, etc.)
, excipients (e.g. magnesium aluminate metasilicate, partially alpha monostarch, microcrystalline cellulose, lactose,
hydrated silicon dioxide, hydroxyprobil starch, etc.)
, a lubricant (e.g., magnesium stearate, talc, hydrogenated oil, etc.), a disintegrant (e.g., croscarmellose sodium type A, carboxymethyl cellulose, etc.), etc. can be added. A powder that adsorbs well, for example, one in which 1 g of the powder adsorbs 2 d or more of liquid, preferably 2.5 ml or more (usually 2 to 4 m, preferably Z5 to
3.5d, especially 2. ．． 7~&4- adsorbing liquid) (hereinafter also referred to as highly absorbent powder) is usually 15~&4-
Nifedipine, EC and HPMC (and RPC if desired) are added to a powder mixture containing about 40% by weight, preferably 20 to 30% by weight, particularly preferably about 25% by weight.
or a powder mixture containing nifedipine, EC and HPMC (and optionally HPMC).
It is convenient that the preparation is made by adsorbing PC). The particle size of the highly absorbent powder is usually 40 to 200 μm.
, preferably 45 to 175 μm, and is preferably a porous powder. Specific examples of highly adsorbent powders include magnesium metasilicate alkinoate, light silicic anhydride, and Hewei hydrotalcite. The powder to be blended in addition to the above-mentioned highly absorbent powder may have a particle size of, for example, 150 to 500 μm, particularly 250 to 3 μm.
A powder having a diameter of 55 μm is preferable, and examples of such powder include crystalline cellulose, partially pregelatinized starch, lactose, hydrated silicon dioxide, and hydroxypropyl starch. Nifedipine, EC and HPMC (
Furthermore, if desired, the above powder mixture is usually blended in an amount of 50 to 800 parts by weight, preferably 150 to 250 parts by weight, per 100 parts by weight of the total amount of RPC. The formulation of the present invention is
For example, it is manufactured as follows. That is, a nifedipine solution is prepared by dissolving nifedipine in a suitable solvent (for example, ethanol, methylene chloride, a mixture of ethanol and methylene chloride, acetone, and a mixture of acetone and ethanol). In this case, it is preferable to use a solubilizing agent (for example, polyoxyl stearate 40, polysorbate 80, polyoxyethylene stearate, sodium lauryl sulfate, etc.). On the other hand, prepare a polymer compound mixed solution by dissolving EC and HPMC or EC, HPMC, and HPC in the same solvent as above. This nifedipine solution and the polymer compound mixed solution are mixed uniformly, and this is sprayed onto a mixed powder of, for example, magnesium metasilicate alsunate, crystalline cellulose, partially pregelatinized starch, lactose, etc. to coat it. Prepare a nifedipine-coated (adsorbed) compound by: The composition can be prepared into tablets, granules, capsules, or
It can be formulated into powders, etc. In particular, the formulation of the present invention can of course be in the form of granules, capsules, powders, etc., and since the nifedipine-coated (adsorbed) composite bottom is easy to tablet, it is extremely easy to tablet. be able to. The formulation of the present invention is usually administered orally. The dosage is about 20 to 40 μ per day as nifedipine,
Administration once or twice a day is enough to achieve its medicinal effects. [Action/Effect] The nifedipine long-acting preparation of the present invention is extremely simple and efficient to manufacture. In addition, according to the nifedipine long-acting preparation of the present invention, nifedipine is rapidly absorbed to an effective blood concentration from the matrix that controls the elution of nifedipine, and the blood concentration is maintained in the therapeutic concentration range for a long period of time, resulting in effective action. Sustainability can be achieved. Therefore, if the preparation of the present invention is used, the number of administrations will be reduced, making it convenient to take and improving compliance, and reducing fluctuations in blood concentration that occur each time the drug is administered, resulting in greater drug efficacy. This has the effect of stabilizing the [Examples] The nifedibine long-acting preparation according to the present invention will be explained below with reference to Examples and Comparative Examples, but the present invention is not limited by these Examples in any way. In addition, in the following description, nifedipine solution refers to nifedipine (20μ) mixed with 40% borioxyl stearate.
(4■) together with ethanol/methylene chloride (weight ratio 6
:4) Refers to the substance dissolved in 120d of mixed liquid. Example 1 EC3■, HPMC18■, HPC9■ (0.15:0.9:0.45 based on the weight of nifedipine) were dissolved in 300 d of a mixture of ethanol and methylene chloride (weight ratio 6:4), and this solution and The nifedipine solution was mixed uniformly.
上記で調製した混合溶液をイノシリン、結晶セルロース
、乳糖、部分アルファ一化デンブンなどに噴霧・コーテ
ィングすることにより組底物を得た。これをクロスカル
メロースナトリウムＡ型とステアリン酸マグネシウムを
加えて混合し打錠した．つづいて、ＨＰＭＣ，マクロゴ
ール６０００、ステアリン酸、酸化チタン、三二酸化鉄
を用いた常法によりフイルムコーティングし、ニフェジ
ピン２０■を含有する錠剤を製造した。A composite bottom was obtained by spraying and coating the mixed solution prepared above on inocinin, crystalline cellulose, lactose, partially alpha starch, etc. This was mixed with croscarmellose sodium type A and magnesium stearate and compressed into tablets. Subsequently, film coating was performed using HPMC, Macrogol 6000, stearic acid, titanium oxide, and iron sesquioxide by a conventional method to produce tablets containing 20 μm of nifedipine.
実施例２
Ｅ Ｃ ４． ５■、ＨＰＭＣＩ６．５■、ＲＰＣ９■
（ニフェジピン重量に対して０． ２ ２ ５ ： ０
． ８ ２ ５ ：０．４５）をエタノール・塩化メチ
レン（重量比６：４）混液３００ｄに溶解し、この溶液
とニフェジピン溶液を均一に混合した．
以下、実施例１と同様にして錠剤を製造した．実施例３
ＥＣ５■、ＨＰＭＣ１ ５■、ＨＰＣ１ ０■（ニフェ
ジピン重量に対して０． ２ ５ ： ０． ７ ５
： ０． ５ ）をエタノール・塩化メチレン（重量比
６：４）混液３００ｄに溶解し、この溶液とニフエジビ
ン溶液を均一に混合した．
以下、実施例１と同様にして錠剤を製造した．実施例４
ＥＣ６■、ＨＰＭＣ２４■（ニフエジビン重量に対して
０．３：１．２）をエタノール・塩化メチレン（重量比
６：４）混液３００１ｄに溶解しこの溶液と、ニフェジ
ピン溶液を均一に混合した．以下、実施例ｌと同様にし
て錠剤を製造した．実施例５
ＥＣ４■、ＨＰＭＣ１６■（ニフェジピン重量に対して
Ｏ．ｌ０．８）をエタノール・塩化メチレン（重量比６
：４）混液３００ｄに溶解しこの溶液と、ニフェジピン
熔液を均一に混合した。Example 2 E C 4. 5■, HPMCI6.5■, RPC9■
(0.2 2 5: 0 relative to nifedipine weight)
．． 8 2 5 :0.45) was dissolved in 300 d of a mixture of ethanol and methylene chloride (weight ratio 6:4), and this solution and nifedipine solution were mixed uniformly. Tablets were manufactured in the same manner as in Example 1. Example 3 EC5■, HPMC15■, HPC10■ (0.25: 0.75 based on nifedipine weight)
: 0. 5) was dissolved in 300 d of a mixture of ethanol and methylene chloride (weight ratio 6:4), and this solution and nifedibine solution were mixed uniformly. Tablets were manufactured in the same manner as in Example 1. Example 4 EC6■ and HPMC24■ (0.3:1.2 based on the weight of nifedipine) were dissolved in 3001d of a mixed solution of ethanol and methylene chloride (weight ratio 6:4), and this solution and the nifedipine solution were uniformly mixed. ．． Tablets were manufactured in the same manner as in Example 1. Example 5 EC4■, HPMC16■ (O.l 0.8 based on the weight of nifedipine) were mixed with ethanol/methylene chloride (weight ratio 6).
:4) Dissolved in 300 d of liquid mixture, and mixed this solution and nifedipine solution uniformly.
以下、実・施例１と同様にして錠剤を製造した。Thereafter, tablets were manufactured in the same manner as in Example 1.
実施例６
ＥＣ２■、ＨＰＭＣ１２■、ＲＰＣ６■（ニフエジビン
重量に対して０．１：０．６：０．３）をエタノール・
塩化メチレン（重量比６：４）混液３００一に溶解し、
この溶液とニフェジピン溶液を均一に混合した。Example 6 EC2■, HPMC12■, RPC6■ (0.1:0.6:0.3 based on the weight of nifedibine) were mixed with ethanol and
Dissolved in 300 parts of methylene chloride (weight ratio 6:4) mixture,
This solution and the nifedipine solution were mixed uniformly.
以下、実施例ｌと同様にして錠剤を製造した。Tablets were produced in the same manner as in Example 1.
実施例７
ＥＣ６■、ＨＰＭＣ５４■（ニフエジビン重量に対して
０．３７２．７）をエタノール・塩化メチレン（重量比
６：４）混液３００ｄに溶解しこの溶液と、ニフェジピ
ン溶液を均一に混合した．以下、実施例ｌと同様にして
錠剤を製造した．実施例８
ＥＣ１２■、ＨＰＭＣ３２■、ＲＰＣ１６■（ニフェジ
ピン重量に対して０．６ ： １．６ ： ０．８）
ヲエタノール・塩化メチレン（重量比６：４）混液３０
０ｄに溶解し、この溶液とニフェジピン溶液を均一に混
合した。Example 7 EC6■ and HPMC54■ (0.372.7% based on the weight of nifedibine) were dissolved in 300 d of a mixture of ethanol and methylene chloride (weight ratio 6:4), and this solution and nifedipine solution were uniformly mixed. Tablets were manufactured in the same manner as in Example 1. Example 8 EC12■, HPMC32■, RPC16■ (0.6: 1.6: 0.8 based on nifedipine weight)
Ethanol/methylene chloride (weight ratio 6:4) mixture 30
This solution and the nifedipine solution were uniformly mixed.
以下、実施例１と同様にして錠剤を製造した．比較例Ｉ
ＨＰＭＣ３０■（ニフェジピン重量に対して１．５）を
エタノール・塩化メチレン（重量比６：４）混液３ ０
０ｄに溶解し、この溶液とニフエジビン溶液を均一に
混合した。Tablets were manufactured in the same manner as in Example 1. Comparative Example I HPMC 30■ (1.5 based on the weight of nifedipine) was mixed with ethanol and methylene chloride (weight ratio 6:4) 30
This solution and the nifedibine solution were uniformly mixed.
以下、実施例１と同様にして錠剤を製造した。Thereafter, tablets were manufactured in the same manner as in Example 1.
比較例２
ＥＣＩＯ■、ＨＰＭＣ２０■（ニフェジピン重量に対し
て０．５：１．０）をエタノール・塩化メチレン（重量
比６ ： ４ ） ？Ｒ液３００Ｉｉに溶解し、この溶
液と、ニフェジピン溶液を均一に混合した。Comparative Example 2 ECIO■, HPMC20■ (0.5:1.0 based on the weight of nifedipine) were mixed with ethanol/methylene chloride (weight ratio 6:4)? It was dissolved in R liquid 300Ii, and this solution and the nifedipine solution were uniformly mixed.
以下、実施例１と同様にして錠剤を製造した．実験例ｌ
（溶出試験）
実施例１〜４および比較例１〜２の錠剤を試料として用
い、下記の通り溶出試験を行った。試験は２Ｉ！．のビ
ーカーに入れた日本薬局方Ｘ■収載の崩壊試験法の第１
液（ＰＨ１．２）２ｍ２中に、試料１錠（ニフエジビン
２０■含有）を加え、日本薬局方Ｘ■収載のパドル法（
回転数１００ｒｐｍ）に準じて行い、経時的にサンプリ
ングし、溶出してきたニフェジピン量を分光光度計（測
定波長３３５ｎｍ）で測定した。その結果は第１図に示
す通りである．
実験例２（血中濃度測定試験）
一夜絶食したビーグル大（体重１２．４〜１５．２ｋｇ
） ４頭に実施例３および４の試料錠剤１錠（ニフェジ
ピン２０■含有）、対照として市販のニフェジピン含有
徐放性製剤をそれぞれニフェジピンとして２０■／頭、
経口投与し、投与後０．５、ｌ、２、３、４、６および
８時間後の血漿中のニフエジビン濃度をクロスオーバー
法により測定した。Tablets were manufactured in the same manner as in Example 1. Experimental example l
(Elution Test) Using the tablets of Examples 1 to 4 and Comparative Examples 1 and 2 as samples, a dissolution test was conducted as described below. The exam is 2I! ．． The first disintegration test method listed in the Japanese Pharmacopoeia X■
Add 1 sample tablet (containing 20 μm of nifedibine) to 2 m2 of liquid (PH1.2), and use the paddle method listed in Japanese Pharmacopoeia
Samples were taken over time, and the amount of nifedipine eluted was measured using a spectrophotometer (measurement wavelength: 335 nm). The results are shown in Figure 1. Experimental Example 2 (Blood Concentration Measurement Test) Beagle-sized (weight 12.4-15.2 kg) fasted overnight
) One sample tablet of Examples 3 and 4 (containing 20 μm of nifedipine) was administered to 4 animals, and as a control, a commercially available nifedipine-containing sustained-release formulation was administered at 20 μm/head as nifedipine.
The drug was administered orally, and the concentration of nifedibine in plasma was measured by a crossover method at 0.5, 1, 2, 3, 4, 6, and 8 hours after administration.
その結果は第２図に示す通りである．血漿中ニフェジピ
ン濃度の測定は、高速液体クロマトグラフ（ＨＰＬＣ）
法により行った．なお、測定条件は下記の通りである．
ＨＰＬＣ定量条件
器機：Ｓｈｉｍａｄｚｕ ＬＣ−３Ａカラム： μ−
Ｂｏｎｄａｓｐｈｅｒｅ Ｃ １ ８ （５ μ）４
１ａｌＸ１５ａｉ
移動相：１％酢酸水溶液：アセトニトリル（５０：５０
）
流速：ｌ．Ｑｄ／細ｉｎ
検出波長：２３８ｎｍ
内標準：ｐ−ヒドロキシ安患香酸ｎ−ブチルThe results are shown in Figure 2. Measurement of plasma nifedipine concentration was performed using high performance liquid chromatography (HPLC).
It was done according to the law. The measurement conditions are as follows. HPLC quantitative conditions equipment: Shimadzu LC-3A column: μ-
Bondasphere C 1 8 (5 μ) 4
1alX15ai Mobile phase: 1% acetic acid aqueous solution: acetonitrile (50:50
) Flow rate: l. Qd/fine detection wavelength: 238 nm Internal standard: p-hydroxybenzate n-butyl
第ｌ図は溶出試験の結果を示すグラフである。 第２図は血中濃度測定試験の結果を示すグラフである． 第１図 ０．５ １．０ ２．０ ３．０ ５．０ ７．０ ｇ１ｔ 間 （ｈ「） FIG. 1 is a graph showing the results of the dissolution test. Figure 2 is a graph showing the results of the blood concentration measurement test. Figure 1 0.5 1.0 2.0 3.0 5.0 7.0 g1t while (h ``)
Claims (2)
シプロピルメチルセルロースよりなり、ニフェジピン１
００重量部に対して、エチルセルロースとヒドロキシプ
ロピルメチルセルロースとが、その総量として１００〜
３００重量部の割合で配合され、かつ、エチルセルロー
ス１００重量部に対して、ヒドロキシプロピルメチルセ
ルロースが４００〜９００重量部の割合で配合されてな
ることを特徴とするニフェジピン持続性製剤。(1) Consisting of nifedipine, ethylcellulose and hydroxypropyl methylcellulose, nifedipine 1
00 parts by weight, the total amount of ethyl cellulose and hydroxypropyl methylcellulose is 100 to 100 parts by weight.
A long-acting preparation of nifedipine, characterized in that it is blended in a ratio of 300 parts by weight, and hydroxypropyl methylcellulose is blended in a ratio of 400 to 900 parts by weight to 100 parts by weight of ethylcellulose.
ロピルメチルセルロースおよびヒドロキシプロピルセル
ロースが配合されてなり、ニフェジピン１００重量部に
対してエチルセルロースとヒドロキシプロピルメチルセ
ルロースとヒドロキシプロピルセルロースとが、その総
量として１００〜３００重量部の割合で配合され、かつ
、エチルセルロース１００重量部に対してヒドロキシプ
ロピルメチルセルロースとヒドロキシプロピルセルロー
スとが、その総量として４００〜９００重量部の割合で
配合されてなることを特徴とするニフェジピン持続性製
剤。(2) Nifedipine, ethylcellulose, hydroxypropylmethylcellulose and hydroxypropylcellulose are blended, and the total amount of ethylcellulose, hydroxypropylmethylcellulose and hydroxypropylcellulose is 100 to 300 parts by weight per 100 parts by weight of nifedipine. 1. A long-acting preparation of nifedipine, characterized in that hydroxypropylmethylcellulose and hydroxypropylcellulose are blended in a total amount of 400 to 900 parts by weight based on 100 parts by weight of ethylcellulose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP205690A JPH03206039A (en) | 1990-01-08 | 1990-01-08 | Nifedipin preparation having prolonged action |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP205690A JPH03206039A (en) | 1990-01-08 | 1990-01-08 | Nifedipin preparation having prolonged action |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03206039A true JPH03206039A (en) | 1991-09-09 |
Family
ID=11518682
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP205690A Pending JPH03206039A (en) | 1990-01-08 | 1990-01-08 | Nifedipin preparation having prolonged action |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03206039A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998047491A3 (en) * | 1997-04-21 | 1999-01-21 | Isa Odidi | Controlled release formulations using intelligent polymers |
| JP2005162733A (en) * | 2003-12-04 | 2005-06-23 | Pfizer Prod Inc | Azithromycin preparation form exhibiting only few adverse effect |
-
1990
- 1990-01-08 JP JP205690A patent/JPH03206039A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998047491A3 (en) * | 1997-04-21 | 1999-01-21 | Isa Odidi | Controlled release formulations using intelligent polymers |
| US6893661B1 (en) | 1997-04-21 | 2005-05-17 | Biovail Corporation | Controlled release formulations using intelligent polymers |
| JP2005162733A (en) * | 2003-12-04 | 2005-06-23 | Pfizer Prod Inc | Azithromycin preparation form exhibiting only few adverse effect |
| JP2010132700A (en) * | 2003-12-04 | 2010-06-17 | Pfizer Prod Inc | Azithromycin dosage form with reduced side effect |
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