JPH0250086B2 - - Google Patents
Info
- Publication number
- JPH0250086B2 JPH0250086B2 JP61316048A JP31604886A JPH0250086B2 JP H0250086 B2 JPH0250086 B2 JP H0250086B2 JP 61316048 A JP61316048 A JP 61316048A JP 31604886 A JP31604886 A JP 31604886A JP H0250086 B2 JPH0250086 B2 JP H0250086B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- quinolone
- compositions
- administration
- active
- 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
- 239000003826 tablet Substances 0.000 claims description 12
- 239000002775 capsule Substances 0.000 claims description 10
- -1 quinolone compound Chemical class 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 3
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000829 suppository Substances 0.000 claims description 3
- 229940030600 antihypertensive agent Drugs 0.000 claims 4
- 239000002220 antihypertensive agent Substances 0.000 claims 4
- UZWAHQKAIZUPJV-UHFFFAOYSA-N 1-methyl-3-methylsulfinylquinolin-4-one Chemical compound C1=CC=C2N(C)C=C(S(C)=O)C(=O)C2=C1 UZWAHQKAIZUPJV-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 24
- 239000000203 mixture Substances 0.000 description 19
- 230000036772 blood pressure Effects 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 230000003276 anti-hypertensive effect Effects 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 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 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 235000019759 Maize starch Nutrition 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 150000007660 quinolones Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 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
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 231100000048 toxicity data Toxicity 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000004916 vomit Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/24—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in positions 2 and 4
- C07D265/26—Two oxygen atoms, e.g. isatoic anhydride
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
本発明は我々が抗高血圧症活性を有することを
見い出した或る群のキノロン化合物を含有する治
療用組成物に関する。さらに特に、本発明は活性
成分として、一般式
（式中、ｎは１または２である）で示されるキ
ノロン化合物を医薬的に許容されうる担体ととも
に含有する降圧剤組成物を提供する。
我々は一般式で示される化合物が有用な抗高
血圧活性を有することを見い出した。温血動物に
非毒性量で投与すると、これらの化合物は上昇し
ている血圧を降下させるのに有効である。
一般式で示される化合物は文献に記載されて
いるが、それらの治療活性はこれらの文献に記載
されていない。たとえば、一般式の範囲内の各
化合物およびそれらの製造方法は、次の刊行物の
一つまたは二つ以上に開示されている：Van
LeusenおよびTaylorによるJ.Org.Cem.33巻、66
〜70頁（1968年）；AlbrechtによるChimie
Therapeutique（1973年）、第１号、45〜48頁；
Connor他によるJ.Heterocyclic Chem.15巻、113
〜114頁（1978年）；Conner他によるJ.
Heterocyclic Chem.15巻、115〜117頁（1978
年）。
本明細書で以後使用するかぎりにおいて、「活
性化合物」の語は一般式で示されるキノロン化
合物を表わす。治療用には、活性化合物は経口、
直腸または非経口で投与でき、経口投与が好まし
い。従つて、本発明の治療用組成物は経口、直腸
または非経口投与用の既知の医薬組成物のいずれ
かの形をとることができる。このような組成物に
使用するに適する医薬品に許容されうる担体は製
剤技術上、良く知らている。本発明の組成物は活
性化合物を0.1−90重量％含有すると適当である。
本発明の組成物は一般に単位投薬形に製剤する。
経口投与用組成物は本発明の好適組成物であ
り、これらはこのような投与に既知の製剤形、た
とえば錠剤、カプセル、シロツプおよび水性また
は油性懸濁液である。これらの組成物の製造に用
いる賦形剤は製剤技術で既知の賦形剤である。錠
剤は活性化合物をリン酸カルシウムのような不活
性稀釈剤と、たとえばマイズデンプンのような崩
壊剤およびたとえばステアリン酸マグネシウムの
ような滑剤の存在下に混合し、次にこの混合物を
既知の方法により錠剤に成形することにより製造
できる。このような錠剤には、所望により既知の
方法、たとえばセルロースアセテートフタレート
の使用により、腸溶性被覆を施すことができる。
同様に、活性化合物を添加賦形剤とともに、また
は膨形剤を加えずに含有するカプセル剤、たとえ
ば硬質または軟質カプセル剤は慣用の方法で製造
でき、所望により既知のやり方で腸溶性被覆を施
してもよい。錠剤およびカプセル剤は通常、活性
化合物５〜500mgをそれぞれ含有できる。経口投
与用のその他の組成物として、たとえば水性媒質
中に活性化合物をナトリウムカルボキシメチルセ
ルロースのような非毒性懸濁剤の存在下に含有す
る水性懸濁液および適当な植物油、たとえばアラ
チス油中に本発明の化合物を含有する油性懸濁液
が包含される。
直腸投与に適する本発明の組成物はこのような
投与に既知の製剤形、たとえばカカオ脂またはポ
リエチレングリコール基材を用いる座薬でありう
る。
非経口投与に適する本発明の組成物はこのよう
な投与に既知の製剤形、たとえば水性および油性
媒質中の殺菌懸濁液または適当な溶媒中の殺菌溶
液である。
いくつかの製剤では、本発明の化合物を非常に
少寸法の、たとえば液体エネルギー粉砕により得
られるような粒子の形で使用すると有利であるこ
ともある。
本発明の組成物では、活性化合物をその他の両
立させうる医薬として活性な成分と組合せること
もできる。
一般式で示されるキノロン化合物治療活性は
(A)自発性高血圧症のラツトに被験化合物を経口投
与する、および(B)正常血圧のラツトに被験化合物
を12指腸投与することを含む試験により証明され
ている。これらの試験は次の方法で行なつた；
試験 Ａ
自発性高血圧症のアオキ−オカモト種で体重
180−240ｇ範囲の雄のラツトを使用する。４群の
ラツトは被検化合物を投与する前夜は絶食させ
る。血圧は次の方法で測定する。ラツトをその尾
がキヤビネツトの穴を通して突き出すようにし
て、38℃に維持されているキヤビネツトに入れ
る。キヤビネツトに入れて30分後に、尾のつけ根
の周囲に配置した膨張しうるカフスを使用して血
圧を測定し、動脈博動を空気脈伝達装置
（pneumatic puke transducer）で追跡する。予
想される血圧り高い圧力をカフスに加え、この圧
力をゆつくり下げる。カフスにおいて動脈博動が
再び現われる圧力を血圧として記録する。ラツト
をキヤビネツトから出し、各群に被験化合物の一
定量を0.25％水性カルボキシメチルセルロース中
の溶液または懸濁液として経口投与する。投与前
の読みに加えて、投与して1.5時間および５時間
後に血圧を測定する。これらの時間のどちらかの
時点で、血圧が20％またはそれ以上減少したなら
ば、その化合物は活性であると判断する。
実験データ
次の結果が得られた。
The present invention relates to therapeutic compositions containing a group of quinolone compounds that we have found to have antihypertensive activity. More particularly, the present invention provides as active ingredient the general formula An antihypertensive composition containing a quinolone compound represented by the formula (wherein n is 1 or 2) together with a pharmaceutically acceptable carrier is provided. We have found that compounds of the general formula have useful antihypertensive activity. When administered in non-toxic doses to warm-blooded animals, these compounds are effective in lowering elevated blood pressure. Compounds of the general formula are described in the literature, but their therapeutic activity is not described in these documents. For example, each compound within the general formula and methods of their preparation are disclosed in one or more of the following publications: Van
J.Org.Cem. by Leusen and Taylor, vol. 33, 66
~70 pages (1968); Chimie by Albrecht
Therapeutique (1973), No. 1, pp. 45-48;
J. Heterocyclic Chem. 15, 113 by Connor et al.
~114 pages (1978); J. Conner et al.
Heterocyclic Chem. vol. 15, pp. 115-117 (1978
Year). As used hereinafter, the term "active compound" refers to a quinolone compound of the general formula. For therapeutic use, the active compound can be administered orally;
It can be administered rectally or parenterally, with oral administration being preferred. Accordingly, the therapeutic compositions of the invention may take the form of any known pharmaceutical compositions for oral, rectal or parenteral administration. Pharmaceutically acceptable carriers suitable for use in such compositions are well known in the pharmaceutical arts. The compositions according to the invention suitably contain 0.1-90% by weight of active compound.
Compositions of the invention will generally be formulated in unit dosage form. Compositions for oral administration are preferred compositions of the invention, and these are the pharmaceutical forms known for such administration, such as tablets, capsules, syrups and aqueous or oily suspensions. The excipients used in the preparation of these compositions are those known in the pharmaceutical art. Tablets are prepared by mixing the active compound with an inert diluent, such as calcium phosphate, in the presence of a disintegrant, such as maize starch, and a lubricant, such as magnesium stearate, and then forming this mixture into tablets by known methods. It can be manufactured by molding. Such tablets may, if desired, be provided with an enteric coating by known methods, eg by the use of cellulose acetate phthalate.
Similarly, capsules containing the active compound with or without added excipients, such as hard or soft capsules, can be manufactured in customary manner and, if desired, provided with an enteric coating in known manner. It's okay. Tablets and capsules can typically each contain from 5 to 500 mg of active compound. Other compositions for oral administration include aqueous suspensions containing the active compound in an aqueous medium in the presence of a non-toxic suspending agent such as sodium carboxymethylcellulose and a suitable vegetable oil, such as Aratis oil. Oily suspensions containing the compounds of the invention are included. Compositions of the invention suitable for rectal administration may be in known formulations for such administration, such as suppositories using cocoa butter or polyethylene glycol bases. Compositions of the invention suitable for parenteral administration are in known formulations for such administration, such as sterile suspensions in aqueous and oily media or sterile solutions in suitable solvents. In some formulations, it may be advantageous to use the compounds of the invention in the form of particles of very small size, such as those obtained by liquid energy milling. In the compositions of the invention, the active compounds can also be combined with other compatible pharmaceutically active ingredients. The therapeutic activity of quinolone compounds represented by the general formula is
Demonstrated by a study involving (A) oral administration of the test compound to spontaneously hypertensive rats, and (B) 12 intradenal administration of the test compound to normotensive rats. These tests were carried out in the following manner; Test A. Body weight in Aoki-Okamoto breeds with spontaneous hypertension.
Male rats in the 180-240 g range are used. Group 4 rats are fasted the night before administration of the test compound. Blood pressure is measured by the following method. The rat is placed in a cabinet maintained at 38°C with its tail protruding through a hole in the cabinet. After 30 minutes in the cabinet, blood pressure is measured using an inflatable cuff placed around the base of the tail, and arterial pulses are tracked with a pneumatic puke transducer. Apply the anticipated high pressure to the cuff and slowly release this pressure. The pressure at which arterial oscillation reappears at the cuff is recorded as blood pressure. The rats are removed from the cabinet and each group is orally administered a fixed amount of the test compound as a solution or suspension in 0.25% aqueous carboxymethyl cellulose. In addition to pre-dose readings, blood pressure is measured at 1.5 and 5 hours post-dose. A compound is considered active if blood pressure decreases by 20% or more at either of these times. Experimental Data The following results were obtained.
【表】
毒性データ
急性毒性LD50（ラツト）は化合物（ｎ＝１）
について測定した。値は400〜800mg／Kgであつ
た。
試験 Ｂ
体重210−240ｇ範囲の雄の正常血圧のラツト
（ウイスター種）を用いる。ラツトに麻酔をかけ、
頚動脈および12指腸にカテーテルを付ける。動脈
カテーテルに連結した圧力伝達装置により、血圧
を電子式で記録する被験化合物は12指腸に0.25％
水性カルボキシメチルセルロース中の溶液または
懸濁液として投与する。血圧は投与前および投与
して30分後に記録する。結果は１薬用量当り３匹
のラツトの測定値の平均値として得る。投与して
30分間に血圧を10％またはそれ以上減少させる化
合物を活性と判断する。
下記の化合物は90mg／Kgまたはそれ以下の薬用
量で試験(A)および(B)の１方または両方において活
性であることが見出された。
１−メチル−３−メチルスルフイニル−４−キ
ノロン
１−メチル−３−メチルスルホニル−４−キノ
ロン。
本発明は高血圧症の温血動物の血圧を降下させ
る方法を提供し、この方法は前記に定義した一般
式で示されるキノロン化合物を投与することに
よりなる。投与は腸内または非経口投与でありう
るが、腸内投与、特に経口投与が好適である。ヒ
トを含む温血動物の高血圧症の治療に適当な薬用
量は単次薬用量または数次薬用量で示して、一般
に0.1〜100mg／Kg／日、さらに通常では0.5〜75
mg／Kg／日、特に１−50mg／Kg／日の範囲内であ
る。単位投薬形は活性化合物を１〜500mg、特に
５〜500mg含有すると適当である。
本発明を次の非限定的例でさらに説明する。
例 １
錠剤の製造において、次の混合物を乾式顆粒化
し、錠剤打錠機で圧縮して、活性成分10mgを含有
する錠剤を作る：
活性成分 10ｇ
乳糖 ５ｇ
リン酸カルシウム ５ｇ
マイズデンプン ５ｇ
同様の方法で、活性成分25mgを含有する錠剤を
作る。
例 ２
例１に記載の方法と同様の方法で、活性成分と
して１−メチル−３−メチルスルフイニル−４−
キノロン10mgまたは25mgを含有する錠剤を作る。
例 ３
腸溶性被覆錠剤の製造において、例１および２
に記載の錠剤に、シエラツクワニスの薄い被膜を
次いでセルロースアセテートフタレートの20枚の
被膜を施す。
例 ４
カプセルの製造において、活性成分とリン酸カ
ルシウムとの等部混合物を硬質ゼラチンカプセル
に封入する。各カプセルは活性成分10mgを含有す
る。
活性成分25mgを含有するカプセルを同様の方法
で作る。
例 ５
例４に記載の方法と同様の方法で、活性成分と
して１−メチル−３−メチルスルフイニル−４−
キノロン10mgまたは25mgを含有するカプセルを作
る。
例 ６
腸溶性被覆カプセルの製造において、例４およ
び５のカプセルを慣用の方法でセルロースアセテ
ートフタレートで被覆する。
例 ７
１ｇの重量を有し、活性成分25mgを含有する座
薬を、次の基材を使用して慣用の方法で作る：
ポリエチレングリコール4000 33％
ポリエチレングリコール6000 47％
水 20％
例２に列挙した適当な活性成分を含有させる。[Table] Toxicity data Acute toxicity LD 50 (rat) indicates compound (n=1)
were measured. The values were 400-800 mg/Kg. Test B Male normotensive rats (Wistar breed) weighing in the range 210-240 g are used. Anesthetize the rat
Place catheters in the carotid artery and 12 dens. Blood pressure is recorded electronically by means of a pressure transmission device connected to an arterial catheter.Test compound is administered at 0.25% into the 12-denum intestine.
Administer as a solution or suspension in aqueous carboxymethylcellulose. Blood pressure is recorded before and 30 minutes after administration. Results are obtained as the average of measurements from 3 rats per dose. Administer
A compound is considered active if it reduces blood pressure by 10% or more in 30 minutes. The compounds listed below were found to be active in one or both of tests (A) and (B) at doses of 90 mg/Kg or less. 1-Methyl-3-methylsulfinyl-4-quinolone 1-Methyl-3-methylsulfonyl-4-quinolone. The present invention provides a method for lowering blood pressure in a hypertensive warm-blooded animal, the method comprising administering a quinolone compound having the general formula defined above. Administration can be enteral or parenteral; enteral administration, especially oral administration, is preferred. Appropriate doses for the treatment of hypertension in warm-blooded animals, including humans, are generally 0.1 to 100 mg/Kg/day, more usually 0.5 to 75 mg/Kg/day, expressed as a single dose or multiple doses.
mg/Kg/day, especially within the range 1-50 mg/Kg/day. Unit dosage forms suitably contain from 1 to 500 mg, especially from 5 to 500 mg, of active compound. The invention is further illustrated in the following non-limiting example. Example 1 In the manufacture of tablets, the following mixture is dry granulated and compressed in a tablet press to make tablets containing 10 mg of active ingredient: 10 g of active ingredient 5 g of lactose 5 g of calcium phosphate 5 g of maize starch Make tablets containing 25 mg of the ingredient. Example 2 In a similar manner to that described in Example 1, 1-methyl-3-methylsulfinyl-4-
Make tablets containing 10 mg or 25 mg of the quinolone. Example 3 In the manufacture of enteric coated tablets, Examples 1 and 2
The tablets described in Table 1 are coated with a thin coat of Sierra varnish followed by 20 coats of cellulose acetate phthalate. Example 4 In the manufacture of capsules, a mixture of equal parts of active ingredient and calcium phosphate is encapsulated in hard gelatin capsules. Each capsule contains 10 mg of active ingredient. Capsules containing 25 mg of active ingredient are made in a similar manner. Example 5 In a similar manner to that described in Example 4, 1-methyl-3-methylsulfinyl-4-
Make capsules containing 10 mg or 25 mg of the quinolone. Example 6 In the production of enteric coated capsules, the capsules of Examples 4 and 5 are coated with cellulose acetate phthalate in a conventional manner. Example 7 Suppositories having a weight of 1 g and containing 25 mg of active ingredient are made in a conventional manner using the following base materials: Polyethylene glycol 4000 33% Polyethylene glycol 6000 47% Water 20% Listed in Example 2 Contain appropriate active ingredients.
Claims (1)
ノロンを含有する降圧剤。 ２ 単位投薬形である特許請求の範囲第１項の降
圧剤。 ３ キノロン化合物は１−メチル−３−メチルス
ルフイニル−４−キノロンである、特許請求の範
囲第１項または第２項に記載の降圧剤。 ４ 錠剤、カプセルまたは座薬の形である、特許
請求の範囲第２項に記載の降圧剤。[Claims] 1. General formula An antihypertensive agent containing a quinolone represented by the formula (wherein n is 1 or 2). 2. The antihypertensive agent of claim 1 which is in unit dosage form. 3. The antihypertensive agent according to claim 1 or 2, wherein the quinolone compound is 1-methyl-3-methylsulfinyl-4-quinolone. 4. The antihypertensive agent according to claim 2, which is in the form of a tablet, capsule, or suppository.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7910558 | 1979-03-27 | ||
| GB7910558 | 1979-03-27 | ||
| GB7939505 | 1979-11-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62215526A JPS62215526A (en) | 1987-09-22 |
| JPH0250086B2 true JPH0250086B2 (en) | 1990-11-01 |
Family
ID=10504143
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3961080A Granted JPS55130960A (en) | 1979-03-27 | 1980-03-27 | Quinolone compound |
| JP61316048A Granted JPS62215526A (en) | 1979-03-27 | 1986-12-24 | Quinolone compound-containing therapeutical composition |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3961080A Granted JPS55130960A (en) | 1979-03-27 | 1980-03-27 | Quinolone compound |
Country Status (10)
| Country | Link |
|---|---|
| JP (2) | JPS55130960A (en) |
| BE (1) | BE882443A (en) |
| CY (1) | CY1343A (en) |
| ES (1) | ES8104232A1 (en) |
| GB (1) | GB2047691B (en) |
| GE (1) | GEP19970835B (en) |
| JO (1) | JO1072B1 (en) |
| MX (1) | MX5950A (en) |
| SU (1) | SU1124886A3 (en) |
| ZA (1) | ZA801575B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA801575B (en) * | 1979-03-27 | 1981-03-25 | Boots Co Ltd | Therapeutic agents |
| IE51542B1 (en) * | 1980-09-26 | 1987-01-07 | Boots Co Ltd | Therapeutic agents |
| DE68917024D1 (en) * | 1988-05-24 | 1994-09-01 | Kirin Brewery | 4 (1H) quinolone derivatives. |
| US8697674B2 (en) | 2004-12-29 | 2014-04-15 | Naturon, Inc. | Xanthurenic acid derivative pharmaceutical compositions and methods related thereto |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55130960A (en) * | 1979-03-27 | 1980-10-11 | Boots Co Ltd | Quinolone compound |
-
1980
- 1980-03-18 ZA ZA00801575A patent/ZA801575B/en unknown
- 1980-03-25 GB GB8010075A patent/GB2047691B/en not_active Expired
- 1980-03-25 CY CY1343A patent/CY1343A/en unknown
- 1980-03-26 JO JO19801072A patent/JO1072B1/en active
- 1980-03-26 BE BE0/199956A patent/BE882443A/en not_active IP Right Cessation
- 1980-03-26 ES ES489929A patent/ES8104232A1/en not_active Expired
- 1980-03-27 JP JP3961080A patent/JPS55130960A/en active Granted
-
1981
- 1981-01-19 SU SU802897803A patent/SU1124886A3/en active
-
1985
- 1985-01-09 MX MX595085A patent/MX5950A/en unknown
-
1986
- 1986-12-24 JP JP61316048A patent/JPS62215526A/en active Granted
-
1994
- 1994-09-07 GE GEAP19942162A patent/GEP19970835B/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55130960A (en) * | 1979-03-27 | 1980-10-11 | Boots Co Ltd | Quinolone compound |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55130960A (en) | 1980-10-11 |
| ES489929A0 (en) | 1981-04-16 |
| JPH0114224B2 (en) | 1989-03-10 |
| CY1343A (en) | 1987-01-16 |
| GB2047691B (en) | 1983-07-20 |
| ZA801575B (en) | 1981-03-25 |
| ES8104232A1 (en) | 1981-04-16 |
| GEP19970835B (en) | 1997-02-10 |
| GB2047691A (en) | 1980-12-03 |
| MX5950A (en) | 1993-11-01 |
| BE882443A (en) | 1980-09-26 |
| JO1072B1 (en) | 1982-07-10 |
| JPS62215526A (en) | 1987-09-22 |
| SU1124886A3 (en) | 1984-11-15 |
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