JPH078799B2 - Platelet aggregation inhibitory composition - Google Patents
Platelet aggregation inhibitory compositionInfo
- Publication number
- JPH078799B2 JPH078799B2 JP2243729A JP24372990A JPH078799B2 JP H078799 B2 JPH078799 B2 JP H078799B2 JP 2243729 A JP2243729 A JP 2243729A JP 24372990 A JP24372990 A JP 24372990A JP H078799 B2 JPH078799 B2 JP H078799B2
- Authority
- JP
- Japan
- Prior art keywords
- platelet aggregation
- aggregation inhibitory
- inhibitory composition
- salt
- acetylsalicylic acid
- 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.)
- Expired - Lifetime
Links
- 208000010110 spontaneous platelet aggregation Diseases 0.000 title claims description 13
- 230000002401 inhibitory effect Effects 0.000 title claims description 11
- 239000000203 mixture Substances 0.000 title claims description 8
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 10
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 10
- KJFRSZASZNLCDF-UHFFFAOYSA-N 1,5-benzothiazepine Chemical class S1C=CC=NC2=CC=CC=C12 KJFRSZASZNLCDF-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 150000001538 azepines Chemical class 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 7
- 230000000694 effects Effects 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- -1 inorganic acid salt Chemical class 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- DWOKUCFPFUCSID-MOPGFXCFSA-N (2s,3s)-8-chloro-5-[2-(dimethylamino)ethyl]-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4-one Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](O)C(=O)N(CCN(C)C)C2=CC=C(Cl)C=C2S1 DWOKUCFPFUCSID-MOPGFXCFSA-N 0.000 description 1
- FTUXVMVEKYLKGE-WECFPGDBSA-N (z)-but-2-enedioic acid;[(2s,3s)-8-chloro-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate Chemical compound OC(=O)\C=C/C(O)=O.C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=C(Cl)C=C2S1 FTUXVMVEKYLKGE-WECFPGDBSA-N 0.000 description 1
- 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 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000007657 benzothiazepines Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 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
- 230000003287 optical effect Effects 0.000 description 1
- 229940100691 oral capsule Drugs 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明は、下記一般式の1,5−ベンゾチアゼピン誘導体
とアセチルサリチル酸を併用することにより、これら化
合物の単独投与に比べて、血小板凝集抑制作用がより高
められた医薬組成物に関する。DETAILED DESCRIPTION OF THE INVENTION (Industrial field of application) The present invention uses a combination of a 1,5-benzothiazepine derivative represented by the following general formula and acetylsalicylic acid to reduce platelet aggregation as compared with single administration of these compounds. The present invention relates to a pharmaceutical composition having a further enhanced inhibitory effect.
（従来の技術及び発明が解決しようとする課題） 本発明における下記一般式（Ｉ）の1,5−ベンゾチアゼ
ピン誘導体は、例えば特公昭63−13994号公報に、降圧
作用、冠血拡張作用、血小板凝集抑制作用などを示す化
合物として知られている。(Prior Art and Problems to be Solved by the Invention) The 1,5-benzothiazepine derivative represented by the following general formula (I) in the present invention is disclosed in, for example, Japanese Patent Publication No. 63-13994, and has an antihypertensive action and a coronary blood dilating action. , And is known as a compound exhibiting an inhibitory effect on platelet aggregation.
一方、アセチルサリチル酸は血小板凝集抑制作用がある
が、胃腸等に対し副作用があるため、その投与量を低く
おさえることが治療上要望されている。On the other hand, acetylsalicylic acid has a platelet aggregation inhibitory action, but since it has a side effect on the gastrointestinal tract and the like, it is therapeutically demanded to keep the dose low.
（課題を解決するための手段） 本発明は、上記の目的のために、下記1,5−ベンゾチア
ゼピン誘導体とアセチルサリチル酸を併用することによ
り、相乗的に血小板凝集抑制作用が増強することを見い
出した。(Means for Solving the Problems) For the above-mentioned purpose, the present invention provides that the following 1,5-benzothiazepine derivative and acetylsalicylic acid are used in combination to synergistically enhance the platelet aggregation inhibitory effect. I found it.
すなわち、本発明は、 一般式 （式中、R1はメチル基を表し、R2は水素原子又はアセチ
ル基を表し、R3及びR4はメチル基を表し、Ｘは塩素原子
を表す） で示される1,5−ベンゾチアゼピン誘導体又はその塩
と、アセチルサリチル酸又はその塩とを含有する血小板
凝集抑制組成物である。That is, the present invention has the general formula (In the formula, R 1 represents a methyl group, R 2 represents a hydrogen atom or an acetyl group, R 3 and R 4 represent a methyl group, and X represents a chlorine atom). A platelet aggregation inhibitory composition comprising an azepine derivative or a salt thereof and acetylsalicylic acid or a salt thereof.
式（Ｉ）の化合物は、ベンゾチアゼピン骨格の２位及び
３位に不斉炭素原子を有するため、２種の立体異性体
（シス、トランス異性）又は４種の光学異性［（＋）−
シス、（−）−シス、（＋）−トランス、（−）−トラ
ンス異性）が存在するが、本発明はこれら異性体又はそ
の混合物をも包含するものであるが、とくに（＋）−シ
ス異性体が好ましい。また、式（Ｉ）の化合物の塩とし
ては、薬学的に許容しうる酸付加塩、例えば塩酸塩、臭
化水素酸塩、硫酸塩、リン酸塩のような無機酸塩、又は
シュウ酸塩、酢酸、マレイン酸塩、フマル酸塩、メタン
スルホン酸塩のような有機酸塩があげられる。The compound of formula (I) has asymmetric carbon atoms at the 2- and 3-positions of the benzothiazepine skeleton, and therefore has two stereoisomers (cis and trans isomers) or four optical isomers [(+)-
Cis, (−)-cis, (+)-trans, (−)-trans isomerism), but the present invention also includes these isomers or a mixture thereof, and particularly (+)-cis. Isomers are preferred. Further, the salt of the compound of formula (I) includes a pharmaceutically acceptable acid addition salt, for example, an inorganic acid salt such as hydrochloride, hydrobromide, sulfate, phosphate, or oxalate. , Organic acid salts such as acetic acid, maleate, fumarate and methanesulfonate.
アセチルサリチル酸は、ナトリウム塩であってもよい。Acetylsalicylic acid may be the sodium salt.
これら両薬剤の配合比率は、1,5−ベンゾチアゼピン誘
導体［Ｉ］１重量部に対し、アセチルサリチル酸を0.3
〜40重量部、とりわけ１〜10重量部とするのが好まし
い。また、一日当りの投与量は、前記の配合比率の範囲
内で、1,5−ベンゾチアゼピン誘導体［Ｉ］が５〜60m
g、とりわけ10〜30mgであり、アセチルサリチル酸が20
〜200mg、とりわけ30〜100mgであるのが好ましい。The compounding ratio of these two drugs is 0.3 parts of acetylsalicylic acid to 1 part by weight of 1,5-benzothiazepine derivative [I].
-40 parts by weight, especially 1-10 parts by weight is preferred. In addition, the daily dose is within the range of the above-mentioned mixing ratio, and the 1,5-benzothiazepine derivative [I] is 5 to 60 m.
g, especially 10-30 mg, 20% acetylsalicylic acid
It is preferably ~ 200 mg, especially 30-100 mg.
本発明の組成物は、経口的又は非経口的に好適な製剤で
あり、経口剤としては錠剤又はカプセルとして、適当な
賦形剤、例えばデン粉、ラクトース、グルコース、リン
酸カルシウム、ステアリン酸を含有することができる。
所望により追加の香料及び／又は甘味剤を含むことがで
きる。注射剤として、適当な安定剤、可溶化剤又は緩衝
剤を含む水を用いることができる。The composition of the present invention is a suitable preparation for oral or parenteral use, and contains a suitable excipient such as den powder, lactose, glucose, calcium phosphate, stearic acid as an oral tablet or capsule. be able to.
If desired, additional flavors and / or sweeteners can be included. Water containing an appropriate stabilizer, solubilizer or buffer can be used as an injection.
（実験例） 血小板凝集抑制作用 （方法） ヒトより採取した血液９容を、3.8％（w/v）クエン酸三
ナトリウム水溶液１容と混和し、該混合物を遠心分離に
より血小板懸濁血漿（PRP）を調製した。残存血液をさ
らに遠心分離して血小板除去血漿（PPP）を調製した。P
RPをPPPで希釈してPRPの血小板数を４×105/mm3に調整
した。PRP175μと下記検体化合物溶液（Ａ）25μ＋
生理食塩水25μ、（Ｂ）25μ＋生理食塩水25μ、
（Ｃ）25μ＋生理食塩水25μ、（Ａ）25μ＋
（Ｃ）25μ又は（Ｂ）25μ＋（Ｃ）25μとの混合
物を、37℃で２分間攪拌後、コラーゲン溶液［ビオキミ
カ・エ・ビオフィジカ・アクタ．、186巻、254頁（1969
年）］25μを加えて血小板凝集を起こさせた。血小板
凝集能はボーンの方法［ネイチャー、194巻、927頁、
（1962年）］により測定し、検体の血小板凝集抑制作用
を求めた。(Experimental example) Platelet aggregation inhibitory action (Method) 9 volumes of blood collected from human was mixed with 1 volume of 3.8% (w / v) trisodium citrate aqueous solution, and the mixture was centrifuged to obtain platelet-suspended plasma (PRP). ) Was prepared. The remaining blood was further centrifuged to prepare platelet-depleted plasma (PPP). P
The RP was diluted with PPP to adjust the platelet count of PRP to 4 × 10 5 / mm 3 . PRP 175μ and the following sample compound solution (A) 25μ +
Physiological saline 25μ, (B) 25μ + physiological saline 25μ,
(C) 25μ + physiological saline 25μ, (A) 25μ +
A mixture of (C) 25 μ or (B) 25 μ + (C) 25 μ was stirred at 37 ° C. for 2 minutes, and then the collagen solution [Biokimica e biophysica ACT. , 186, 254 (1969
25 μl) was added to induce platelet aggregation. Platelet Aggregation Ability is Born's Method [Nature, 194, 927,
(1962)] and the platelet aggregation inhibitory effect of the sample was determined.
なお、生理食塩水50μのみを加えたものを、非投薬対
照とした。The non-medication control was prepared by adding 50 μl of physiological saline.
（検体化合物） （Ａ） （＋）−シス−２−（４−メトキシフェニル）
−３−アセトキシ−５−［２−（ジメチルアミノ）エチ
ル］−８−クロロ−2,3−ジヒドロ−1,5−ベンゾチアゼ
ピン−４（5H）−オン・マレイン酸塩（R1、R3、R4＝CH
3、R2＝CH3CO、Ｘ＝Cl） （Ｂ） （＋）−シス−２−（４−メトキシフェニル）
−３−ヒドロキシ−５−［２−（ジメチルアミノ）エチ
ル］−８−クロロ−2,3−ジヒドロ−1,5−ベンゾチアゼ
ピン−４（5H）−オン（R1,R3,R4＝CH3、R2＝Ｈ、Ｘ＝C
l） （Ｃ） アセチルサリチル酸 （結果） （発明の効果） 上記実験結果から明らかなように、本発明の医薬組成物
は、それに含有する式（Ｉ）の化合物又はアセチルサリ
チル酸をそれぞれ単独投与した場合に比べ、高い血小板
凝集抑制効果を示し、顕著な相乗効果があることがわか
る。従って同一の効果を奏するのに薬量を低減すること
ができるので、極めて安全であり、かつ高い効果が得ら
れる。(Sample compound) (A) (+)-cis-2- (4-methoxyphenyl)
-3-acetoxy-5- [2- (dimethylamino) ethyl] -8-chloro-2,3-dihydro-1,5-benzothiazepin-4 (5H) -one maleate (R 1 , R 3 , R 4 = CH
3 , R 2 = CH 3 CO, X = Cl) (B) (+)-cis-2- (4-methoxyphenyl)
3-hydroxy-5- [2- (dimethylamino) ethyl] -8-chloro-2,3-dihydro-1,5-benzothiazepin -4 (5H) - on (R 1, R 3, R 4 = CH 3 , R 2 = H, X = C
l) (C) Acetylsalicylic acid (result) (Effect of the Invention) As is clear from the above experimental results, the pharmaceutical composition of the present invention exhibits a higher platelet aggregation inhibitory effect than when the compound of formula (I) or acetylsalicylic acid contained therein is administered alone. It turns out that there is a remarkable synergistic effect. Therefore, the dose can be reduced to achieve the same effect, which is extremely safe and has a high effect.
Claims (2)
ル基を表し、R3及びR4はメチル基を表し、Ｘは塩素原子
を表す） で示される1,5−ベンゾチアゼピン誘導体又はその塩
と、アセチルサリチル酸又はその塩とを含有する血小板
凝集抑制組成物。1. A general formula (In the formula, R 1 represents a methyl group, R 2 represents a hydrogen atom or an acetyl group, R 3 and R 4 represent a methyl group, and X represents a chlorine atom). A platelet aggregation inhibitory composition comprising an azepine derivative or a salt thereof and acetylsalicylic acid or a salt thereof.
シス体である請求項１記載の血小板凝集抑制組成物。2. A 1,5-benzothiazepine derivative is (+)-
The platelet aggregation inhibitory composition according to claim 1, which is a cis form.
Priority Applications (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2243729A JPH078799B2 (en) | 1990-09-17 | 1990-09-17 | Platelet aggregation inhibitory composition |
| CA002049655A CA2049655C (en) | 1990-09-17 | 1991-08-21 | Pharmaceutical composition for inhibiting platelet aggregation |
| AT91307773T ATE106734T1 (en) | 1990-09-17 | 1991-08-23 | PHARMACEUTICAL COMPOSITION TO PREVENT PLATELET AGGREGATION. |
| ES91307773T ES2057777T3 (en) | 1990-09-17 | 1991-08-23 | PHARMACEUTICAL COMPOSITION TO INHIBIT THE PLATELET AGGREGATION. |
| EP91307773A EP0476854B1 (en) | 1990-09-17 | 1991-08-23 | Pharmaceutical composition for inhibiting platelet aggregation |
| DE69102379T DE69102379T2 (en) | 1990-09-17 | 1991-08-23 | Pharmaceutical composition for preventing platelet aggregation. |
| DK91307773.1T DK0476854T3 (en) | 1990-09-17 | 1991-08-23 | Pharmaceutical composition to inhibit platelet aggregation |
| KR1019910016103A KR0145689B1 (en) | 1990-09-17 | 1991-09-16 | Pharmaceutical composition for inhibiting platelet aggregation |
| FR9111435A FR2666741B1 (en) | 1990-09-17 | 1991-09-17 | THERAPEUTIC COMPOSITION FOR INHIBITING PLATELET AGGREGATION. |
| US08/035,895 US5387581A (en) | 1990-09-17 | 1993-03-23 | Pharmaceutical composition of aspirin and a benzothiazepine for inhibiting platelet aggregation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2243729A JPH078799B2 (en) | 1990-09-17 | 1990-09-17 | Platelet aggregation inhibitory composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04128233A JPH04128233A (en) | 1992-04-28 |
| JPH078799B2 true JPH078799B2 (en) | 1995-02-01 |
Family
ID=17108125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2243729A Expired - Lifetime JPH078799B2 (en) | 1990-09-17 | 1990-09-17 | Platelet aggregation inhibitory composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH078799B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2087743C (en) * | 1992-02-06 | 1999-04-27 | Akio Odawara | Pharmaceutical composition for inhibiting platelet aggregation |
| JP2712143B2 (en) * | 1992-12-22 | 1998-02-10 | 田辺製薬株式会社 | Platelet aggregation inhibiting composition |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8406318D0 (en) * | 1984-03-10 | 1984-04-11 | Tanabe Seiyaku Co | 1 5-benzothiazepine derivatives |
| GB8410949D0 (en) * | 1984-04-28 | 1984-06-06 | Tanabe Seiyaku Co | 1 5-benzothiazepine derivatives |
| FR2589358B1 (en) * | 1985-07-30 | 1987-12-04 | Synthelabo | PHARMACEUTICAL COMPOSITIONS BASED ON DILTIAZEM AND ASPIRIN |
-
1990
- 1990-09-17 JP JP2243729A patent/JPH078799B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH04128233A (en) | 1992-04-28 |
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