JPS62283926A - Long-acting composition of nicardipine hydrochloride - Google Patents
Long-acting composition of nicardipine hydrochlorideInfo
- Publication number
- JPS62283926A JPS62283926A JP12568786A JP12568786A JPS62283926A JP S62283926 A JPS62283926 A JP S62283926A JP 12568786 A JP12568786 A JP 12568786A JP 12568786 A JP12568786 A JP 12568786A JP S62283926 A JPS62283926 A JP S62283926A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- nicardipine hydrochloride
- long
- hydrochloride
- water
- 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
- AIKVCUNQWYTVTO-UHFFFAOYSA-N nicardipine hydrochloride Chemical group Cl.COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 AIKVCUNQWYTVTO-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229960002289 nicardipine hydrochloride Drugs 0.000 title claims abstract description 28
- 239000000203 mixture Substances 0.000 title claims abstract description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 12
- 150000007524 organic acids Chemical class 0.000 claims abstract description 12
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 12
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims abstract description 9
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229920000609 methyl cellulose Polymers 0.000 claims abstract description 6
- 239000001923 methylcellulose Substances 0.000 claims abstract description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims abstract description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims abstract description 4
- 235000015165 citric acid Nutrition 0.000 claims abstract description 4
- 239000011975 tartaric acid Substances 0.000 claims abstract description 4
- 235000002906 tartaric acid Nutrition 0.000 claims abstract description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 3
- 239000001361 adipic acid Substances 0.000 claims abstract description 3
- 235000011037 adipic acid Nutrition 0.000 claims abstract description 3
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 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
- 230000005923 long-lasting effect Effects 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 7
- 235000010981 methylcellulose Nutrition 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 235000011087 fumaric acid Nutrition 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 1
- 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 1
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 abstract description 2
- 125000004494 ethyl ester group Chemical group 0.000 abstract description 2
- 238000013329 compounding Methods 0.000 abstract 2
- 239000007788 liquid Substances 0.000 abstract 1
- 239000003509 long acting drug Substances 0.000 abstract 1
- 238000009472 formulation Methods 0.000 description 7
- 239000008187 granular material Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- 238000010828 elution Methods 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000001856 Ethyl cellulose Substances 0.000 description 3
- 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 description 3
- 229920001249 ethyl cellulose Polymers 0.000 description 3
- 235000019325 ethyl cellulose Nutrition 0.000 description 3
- 239000001384 succinic acid Substances 0.000 description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 2
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 229940027223 nicardipine hydrochloride 20 mg Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920003136 Eudragit® L polymer Polymers 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- -1 N-benzyl-N-methylamino Chemical group 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229960003403 betaine hydrochloride Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- HOPSCVCBEOCPJZ-UHFFFAOYSA-N carboxymethyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC(O)=O HOPSCVCBEOCPJZ-UHFFFAOYSA-N 0.000 description 1
- 229940099352 cholate Drugs 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- IWVKTOUOPHGZRX-UHFFFAOYSA-N methyl 2-methylprop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.COC(=O)C(C)=C IWVKTOUOPHGZRX-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
３、発明の詳細な説明
本発明は塩酸ニカルジピン〔２，６−ノメチルー４−（
３’−二トロフェニル）−１，４−ジヒドロビリノン−
３，５−ンカルポン酸−３−メチルエステル−５−β−
（Ｎ−ベンジル−Ｎ−メチルアミノ）エチルエステル塩
酸塩〕を含有する塩酸ニカルジピン経口組成物に関する
。Detailed Description of the Invention 3. Detailed Description of the Invention The present invention provides nicardipine hydrochloride [2,6-nomethyl-4-(
3'-ditrophenyl)-1,4-dihydrobirinone-
3,5-carboxylic acid-3-methyl ester-5-β-
(N-benzyl-N-methylamino)ethyl ester hydrochloride].
塩酸ニカルジピンは低１）Ｈ領域に対する溶解性は良好
であるか高ｐ ｒ−ｒ領域では極めて溶解性か・思い。I wonder if nicardipine hydrochloride has good solubility in the low 1)H region, or extremely solubility in the high prr region.
従って塩酸ニカルジピンを含有する医薬製剤はじ、しう
ぶんに長時間酸性領域に留まっている場合にだけ製剤か
らの薬物放出は良好であり吸収が可能になる。即ち、溶
解性および吸収が胃および揚上部器管内のｐＨおよび滞
留時間に太き（依存する。Therefore, pharmaceutical formulations containing nicardipine hydrochloride will only have good drug release and absorption from the formulation if they remain in the acidic region for a sufficiently long period of time. That is, solubility and absorption depend on pH and residence time in the stomach and upper organ.
持続性製剤は、使用時の便宜、血中濃度を有効血中濃度
に保つなど治療上多くの利点を何する。Long-acting formulations offer many therapeutic advantages, such as convenience in use and maintaining effective blood concentrations.
欠点として個体間、９＋体内の血中濃度のバラツキが大
きくパイオアベラリティーら低くなる傾向を示すことな
どが挙げられるが、上記特徴を有する塩酸ニカルジピン
を通常の方法で持続化する場合これらの欠点が現れ易く
なることか考えられる。Disadvantages include large variations in blood concentration between individuals and within the body, and a tendency to lower pyroavailability.However, if nicardipine hydrochloride, which has the above characteristics, is sustained by a normal method, these disadvantages will be avoided. I think it might be easier to appear.
本発明らは、これらの問題に対し、塩酸ニカルジピンに
有機酸、水溶性高分子化合物を配合することにより製剤
に浸透する溶出液を低１）Ｈ領域に保つことで塩酸ニカ
ルジピンの溶解性が改善され、これを通常の方法により
持続化することで、ｐｔｔ依存性の少ない薬物放出を示
す塩酸ニカルジピン持続性製剤が容易に得られることを
見出し本発明を完成するに至った。In order to solve these problems, the present inventors have improved the solubility of nicardipine hydrochloride by keeping the eluate that permeates the formulation in the low 1) H range by blending nicardipine hydrochloride with an organic acid and a water-soluble polymer compound. The present inventors have discovered that by sustaining this using a conventional method, a long-lasting preparation of nicardipine hydrochloride exhibiting less PTT-dependent drug release can be easily obtained, leading to the completion of the present invention.
本発明による塩酸ニカルジピン持続性製剤は、塩酸ニカ
ルジピンに有機酸、水溶性高分子化合物を配合した後は
通常の方法による持続化の適用が可能である。持続化の
例としては、塩酸ニカルジピン、有機酸及び水溶性高分
子化合物の混合物と溶解度の小さいあるいは溶解速度の
遅い物質を混和または分散させる方法、上記混合物を含
む易溶性製剤に旧法と同様な非親水性物質を被覆する方
法などが挙げられる。The sustained-release preparation of nicardipine hydrochloride according to the present invention can be applied for sustained use by a conventional method after blending nicardipine hydrochloride with an organic acid and a water-soluble polymer compound. Examples of sustainability include a method of mixing or dispersing a mixture of nicardipine hydrochloride, an organic acid, and a water-soluble polymer compound with a substance with low solubility or a slow dissolution rate, and a method of mixing or dispersing a mixture of nicardipine hydrochloride, an organic acid, and a water-soluble polymer compound; Examples include a method of coating a hydrophilic substance.
本発明で用いられる有機酸としてはクエン酸。The organic acid used in the present invention is citric acid.
酒石酸、コハク酸、アジピン酸、フマル酸、マレイン酸
、リンゴ酸、アスコルビン酸またはこれらの酸の２種以
上の混合物を挙げることができるが、乳酸、ベタイン塩
酸塩、繊維系グリコール酸、酒石酸もしくはクエン酸の
モノナトリウムもしくはモノカリウム塩も使用できる。Mention may be made of tartaric acid, succinic acid, adipic acid, fumaric acid, maleic acid, malic acid, ascorbic acid or mixtures of two or more of these acids, but also lactic acid, betaine hydrochloride, fibrous glycolic acid, tartaric acid or citric acid. The monosodium or monopotassium salt of the acid can also be used.
有機酸の配合割合として塩酸ニカルジピン１部当り０．
５部から上限については有機酸が生理的に特に影響を与
えないこと、製剤上特に問題が生じない範囲であれば特
に限定せずとら良い。The blending ratio of organic acid is 0.00% per part of nicardipine hydrochloride.
The upper limit from 5 parts may be set without particular limitation as long as the organic acid does not have any particular physiological effects and does not cause any particular problems in terms of formulation.
水溶性高分子化合物としてはメチルセルロース。Methylcellulose is a water-soluble polymer compound.
ヒドロキシプロピルセル０−ス、ヒドロキンプロピルメ
チルセルロース及び一般的に用いられる医薬用水溶性高
分子化合物またはこれらの２種以上の混合物を挙げるこ
とができる。水溶性高分子の配合割合として塩酸ニカル
ジピン１部当り０．５〜３．０部用いる。Examples include hydroxypropylcellulose, hydroquinpropylmethylcellulose, commonly used pharmaceutical water-soluble polymer compounds, or mixtures of two or more thereof. The mixing ratio of the water-soluble polymer is 0.5 to 3.0 parts per part of nicardipine hydrochloride.
次に本発明を以下の参考例 実、施例を挙げて具体的に
説明するが、本発明はこれらに限定されるものではない
。Next, the present invention will be specifically explained with reference to the following reference examples, but the present invention is not limited thereto.
参考例−１
下記処方に従い通常の湿式法で持続性基酸二カルノピン
錠を作製した。Reference Example-1 A long-lasting dicarnopine tablet was prepared by a conventional wet method according to the following formulation.
処方
塩酸ニカルジピン ２０ ｍｇ
ハイドロキノプロピルメチルセルロースフタレート（Ｈ
Ｐ −５５Ｆ） ７．５ｍｇ乳糖
１２４．５ｍｇエチル
セルロース １．５ｍｇ１５５
．０１１１ｇ
実施例−１
下記処方に従い持続性塩酸ニカルジピン錠を作製した。Prescription nicardipine hydrochloride 20 mg
Hydroquinopropyl methylcellulose phthalate (H
P-55F) 7.5mg lactose
124.5mg ethylcellulose 1.5mg155
．． 0111g Example-1 Long-acting nicardipine hydrochloride tablets were prepared according to the following formulation.
処方
塩酸ニカルジピン ２０ ｍｇ
コハク酸 ２０
ｍｇの
メチルセルロース（ＳＭ−８０００） ２０
ｍｇ硬化油 １２
ｍｇハイ・ドロキシプロピルメチルセルロースフタレー
ト（Ｈ１’−５５°Ｆ） ４．５ｍｇ
乳糖 ７３ ｍｇ
エチルセルロース ｔ、５ｍｇ
１５２．５ｍｇ
得られた対照試料（参考例１）及び本発明品（実施例１
）の溶出試験を日間パドル法により行った。Prescription nicardipine hydrochloride 20 mg
Succinic acid 20
mg methylcellulose (SM-8000) 20
mg hydrogenated oil 12
mg Hydroxypropyl methylcellulose phthalate (H1'-55°F) 4.5mg
Lactose 73 mg
Ethylcellulose t, 5mg
152.5 mg The obtained control sample (Reference Example 1) and the product of the present invention (Example 1)
) was conducted using the daily paddle method.
試験液は、ｐＨ６，５（０，０５Ｍリン酸緩衝液）及び
ｐ夏−＋１．２（日間第−液）９００ｍ、／を使用する
。The test solutions used are pH 6.5 (0.05M phosphate buffer) and psum-+1.2 (day-1 solution) 900m//.
結果を図１９図２に示す。The results are shown in Figure 19 and Figure 2.
実施例−２
下記処方に従い、押し出し造粒法により１２〜４２ Ｍ
ｅｓ’ｈの易溶性顆粒を作製した。Example-2 12 to 42 M by extrusion granulation method according to the following recipe
Easily soluble granules of es'h were prepared.
処方
塩酸ニカルジピン ４０ｍｇコ
ハク酸 ８０Ｂメ
チルセルロース（ＳＭ −８０００） ４０ｍ
ｇ乳糖 ９８ｍｇ
繊維系ゲルコール酸カルシウム
（Ｅ ＣＧ −５０５）
３０ｍｇ３００ｍｇ
得られた易溶性顆粒に対し下記フィルム液処方にて顆粒
重量の１５％のフィルムを被覆し持続性塩酸ニカルジピ
ン顆粒を作製した。Prescription Nicardipine Hydrochloride 40mg Succinic Acid 80B Methyl Cellulose (SM-8000) 40m
g Lactose 98mg
Fibrous gel cholate calcium (ECG-505)
30mg300mg The obtained easily soluble granules were coated with a film having an amount of 15% of the granule weight using the following film liquid formulation to produce long-lasting nicardipine hydrochloride granules.
処方
ハイドロキシプロピルメチルセルロースフタレート（Ｈ
Ｐ−５５°！ｌ′） １０部硬化
油 ７部エタノー
ル １００部塩化メ
チレン １００部実施例−
３
実施例−２で得られた易溶性顆粒に対し下記フィルム液
処方にて顆粒重量の２０％のフィルムを被覆し持続性塩
酸ニカルジピン顆粒を作製した。Prescription Hydroxypropyl Methyl Cellulose Phthalate (H
P-55°! l') 10 parts Hydrogenated oil 7 parts Ethanol 100 parts Methylene chloride 100 parts Example-
3 The easily soluble granules obtained in Example 2 were coated with a film having an amount of 20% of the granule weight using the following film liquid formulation to produce long-lasting nicardipine hydrochloride granules.
処方
メチルメタアクリレートメタアクリル酸コーポリマー（
オイドラギット Ｌ） １０部エチルセルロ
ース ２部ステアリン酸
３部タルク
３部エタノール
１００部塩化メチレン
１（ＩＱ部実施例−４
下記処方の各成分を均一に混合し粉末打錠し持続性塩酸
ニカルジピン綻を作製した。Formulated Methyl Methacrylate Methacrylic Acid Copolymer (
Eudragit L) 10 parts ethyl cellulose 2 parts stearic acid
3 part talc
3 parts ethanol
100 parts methylene chloride
1 (IQ Section Example-4) Each component of the following formulation was mixed uniformly and compressed into a powder tablet to prepare a long-lasting solution of nicardipine hydrochloride.
処方
塩酸ニカルジピン ４０ｍｇコ
ハク酸 ８０ｍｇ
メヂルメチルーズ（ＳＭ−８，０００） ４０ｍ
ｇ乳糖 １０５ｍ
ｇカルボキンビニルポリマー
（ハイヒスワコー） ３０
ｍｇ繊維系グリコール酸カルンウム ５ｍ
ｇ（ＥＣＧｔ０５）
００ｍｇPrescription nicardipine hydrochloride 40mg succinic acid 80mg
Medyl methyl rose (SM-8,000) 40m
g lactose 105m
g Carboquine vinyl polymer (Hihiswako) 30
mg fiber-based carunium glycolate 5m
g(ECGt05) 00mg
図１は参考例−■（対照試料）の溶出試験結果を示す図
である。
図２は実施例−１（本発明品）の溶出試験結果を示す図
である。
特許出頭入 日本ケミファ株式会社
代表者丑山圭三
溶出時間（ｈｒ）
溶出時間（ｈｒ）FIG. 1 is a diagram showing the elution test results of Reference Example-■ (control sample). FIG. 2 is a diagram showing the elution test results of Example-1 (product of the present invention). Patent filing by Nippon Chemifa Co., Ltd. Representative Keizo Ushiyama Elution time (hr) Elution time (hr)
Claims (5)
合物とを含有することを特徴とする塩酸ニカルジピン持
続性組成物。(1) A long-lasting composition of nicardipine hydrochloride, which contains nicardipine hydrochloride, an organic acid, and a water-soluble polymer compound.
酸、フマル酸、マレイン酸、リンゴ酸、アスコルビン酸
またはこれらの混合物である特許請求の範囲第（１）項
記載の持続性組成物。(2) The long-lasting composition according to claim (1), wherein the organic acid is citric acid, tartaric acid, succinic acid, adipic acid, fumaric acid, maleic acid, malic acid, ascorbic acid, or a mixture thereof.
０．５部以上である特許請求の範囲第（１）項記載の持
続性組成物。(3) The long-lasting composition according to claim (1), wherein the blending ratio of the organic acid is 0.5 part or more to 1 part of nicardipine hydrochloride.
キシプロピルセルロース、ヒドロキシプロピルメチルセ
ルロースまたはこれらの混合物である特許請求の範囲第
（１）項記載の持続性組成物。(4) The long-lasting composition according to claim (1), wherein the water-soluble polymer compound is methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, or a mixture thereof.
ン１部に対し０．５〜３．０部である特許請求の範囲第
（１）項記載の持続性組成物。(5) The long-lasting composition according to claim (1), wherein the proportion of the water-soluble polymer compound is 0.5 to 3.0 parts per 1 part of nicardipine hydrochloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12568786A JPS62283926A (en) | 1986-06-02 | 1986-06-02 | Long-acting composition of nicardipine hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12568786A JPS62283926A (en) | 1986-06-02 | 1986-06-02 | Long-acting composition of nicardipine hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62283926A true JPS62283926A (en) | 1987-12-09 |
Family
ID=14916196
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12568786A Pending JPS62283926A (en) | 1986-06-02 | 1986-06-02 | Long-acting composition of nicardipine hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62283926A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0267219A (en) * | 1988-09-02 | 1990-03-07 | Eisai Co Ltd | Oral pharmaceutical composition containing cyclic amine derivative |
| JP2006096771A (en) * | 1992-07-29 | 2006-04-13 | Gacell Lab Ab | Controlled release morphine preparation |
| WO2006118210A1 (en) * | 2005-04-28 | 2006-11-09 | Eisai R & D Management Co., Ltd. | Method of preventing dihydropyridine compound from degradation |
| JP2007182451A (en) * | 1996-03-04 | 2007-07-19 | Sanofi-Aventis | Sustained-release pharmaceutical formulation containing mizolastine |
-
1986
- 1986-06-02 JP JP12568786A patent/JPS62283926A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0267219A (en) * | 1988-09-02 | 1990-03-07 | Eisai Co Ltd | Oral pharmaceutical composition containing cyclic amine derivative |
| JP2006096771A (en) * | 1992-07-29 | 2006-04-13 | Gacell Lab Ab | Controlled release morphine preparation |
| JP2007182451A (en) * | 1996-03-04 | 2007-07-19 | Sanofi-Aventis | Sustained-release pharmaceutical formulation containing mizolastine |
| WO2006118210A1 (en) * | 2005-04-28 | 2006-11-09 | Eisai R & D Management Co., Ltd. | Method of preventing dihydropyridine compound from degradation |
| JP5103173B2 (en) * | 2005-04-28 | 2012-12-19 | エルメッド エーザイ株式会社 | Method for preventing decomposition of dihydropyridine compounds |
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