JPS58152821A - Blended drug - Google Patents
Blended drugInfo
- Publication number
- JPS58152821A JPS58152821A JP3694382A JP3694382A JPS58152821A JP S58152821 A JPS58152821 A JP S58152821A JP 3694382 A JP3694382 A JP 3694382A JP 3694382 A JP3694382 A JP 3694382A JP S58152821 A JPS58152821 A JP S58152821A
- Authority
- JP
- Japan
- Prior art keywords
- alginate
- drug
- water
- active ingredient
- side effects
- 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
Abstract
Description
【発明の詳細な説明】
本発明は新しい配合医薬品、更に詳しくは副作用として
消化管障害を惹起する医薬品に、アルｆシ酸の水溶性塩
類を配合することによって、該医薬品本来の薬理作用は
全く低下させることなく、むしろよシ改善し、しかもそ
の副作用を顕著に軽減乃至抑制した配合医薬品に関する
。DETAILED DESCRIPTION OF THE INVENTION The present invention provides a new compounded drug, more specifically, a drug that causes gastrointestinal disorders as a side effect, by incorporating water-soluble salts of alf-sialic acid, thereby completely eliminating the original pharmacological action of the drug. The present invention relates to a combination drug that does not cause any deterioration but rather improves the health of the patient, and also significantly reduces or suppresses side effects.
従来より主として経口投与される医薬品中には、副作用
として消化管障害を惹起するものが数多く存在している
。例えば最も使用頻度の高い医薬品のひとつである解熱
鎮痛剤としてのアスピリン等、抗炎症剤としてのフェニ
ルブタリン１インドメタシン、メフェナム酸等、降圧・
鎮痛剤としてのしｔルじシ等・ステ０イド本ルｔシであ
るコーチリン等はその薬効が優れている反面で消化管障
害例えば胃びらん、出血、潰瘍等の副作用を惹起するこ
とが知られている。従って２等医薬品はその使用に当っ
ては本来の薬効と上記副作用とのバラシスを充分に考慮
し、慎重な投薬管理を余儀なくされている実情にある。BACKGROUND OF THE INVENTION Conventionally, there are many drugs that are mainly orally administered that cause gastrointestinal disorders as side effects. For example, aspirin is an antipyretic analgesic, which is one of the most frequently used medicines, phenylbutaline, indomethacin, mefenamic acid, etc. are anti-inflammatory agents, antihypertensive agents, and mefenamic acid.
Corchiline, which is used as an analgesic and a steroid, has excellent medicinal efficacy, but is known to cause side effects such as gastrointestinal disorders, such as gastric erosion, bleeding, and ulcers. It is being Therefore, when using second class drugs, it is necessary to carefully manage the dosage by fully considering the balance between the original medicinal efficacy and the above-mentioned side effects.
特に−作用として胃潰瘍を誘発することの知られている
代表的な医薬品のひとつであるアスピリンは、実際に臨
床使用によシしばしば消化性潰瘍を伴う。その好発部位
は胃小彎側、幽門前庭部であシ、胃粘膜に対する直接障
害作用がその発生機序とされている。該アスじリンには
また胃液分泌光通作用、出自傾向助長作用のあることが
知られ、実験的に潰瘍を惹起させる薬物としても熟知さ
れている。従って上記各種医薬品の適用に当っては、惹
起されるおそれのある急性胃炎性出血、びらん、潰瘍等
の消化管−書の防止、減弱対策が要望されているが、現
在かかるｇｍを解消する対策は皆無に等しい。In particular, aspirin, which is one of the representative drugs known to induce gastric ulcers, is often accompanied by peptic ulcers in clinical use. Its most common sites are the lesser curvature of the stomach and the antrum of the pylorus, and its mechanism of occurrence is thought to be direct damage to the gastric mucosa. Asdilin is also known to have a phototransmissive effect on gastric juice secretion and an effect on promoting the propensity for birth, and is also well known as a drug that experimentally induces ulcers. Therefore, when applying the various pharmaceuticals mentioned above, there is a need for measures to prevent and attenuate gastrointestinal problems such as acute gastritis bleeding, erosions, and ulcers that may be caused.Currently, measures are being taken to eliminate such problems. is the same as nothing.
本発明は上記問題をみごとに解消し、副作用を伴うこと
なく極めて安全に適用できる新しい配合医薬品を提供す
ることを目的とするものである。The object of the present invention is to successfully solve the above problems and provide a new combination drug that can be applied extremely safely without side effects.
即ち本発明は、副作用として消化管障害を惹起する医薬
品に、アルイン酸の水溶性塩類を配合したことを特徴と
する配合医薬品に係る。That is, the present invention relates to a combination drug characterized in that a water-soluble salt of alinic acid is added to a drug that causes gastrointestinal disorders as a side effect.
本発明者らは、従来より医薬分野において用いられる各
種の薬剤につき鋭意研究を重ねる過程において、古くか
ら製剤原料、膨張性緩下剤、血漿増量剤等として用いら
れていたアル４：ＪＦＩＲナトリウムを始めとするアル
イン酸の水溶性塩類が、消化管粘膜保−作用及び消化管
止血作用を有し、消化性潰瘍治療剤として有用であると
の知見を得たが、今般偶然にも才略水溶性塩類がアスピ
リン等の医薬品との併用によって、２等医薬品本来の薬
効を全く低下させることなく、その副作用のみを事実を
発晃した。本発明はこの新しい知見に基づき完成された
ものである。In the process of intensive research into various drugs conventionally used in the pharmaceutical field, the present inventors discovered Al-4:JFIR sodium, which has long been used as a pharmaceutical raw material, bulking laxative, plasma expander, etc. It has been found that water-soluble salts of alinic acid have gastrointestinal mucosal-preserving and gastrointestinal hemostatic effects and are useful as therapeutic agents for peptic ulcers. When used in combination with pharmaceuticals such as aspirin, it was discovered that only the side effects occurred without any reduction in the original efficacy of secondary drugs. The present invention was completed based on this new knowledge.
本発明の配合医薬品は、その有効成分化合物と共にアル
ｆ：／＃の水溶性塩類を配合することを必須とし、これ
に基づいて、有効成分化合物本来の薬効を低減させるこ
となく、その−作用を顕著に低減乃至防止できる。ここ
で利用されるアルイン酸の水溶性塩類としてはアルイン
酸のすトリウム塩・カリウム塩、アン七ニウム塩、アミ
ン塩等を例示できる。上記アルイン酸は、昆布、かじめ
、あらぬ等の４１１１の細胞壁及びＳ胞間にカルシウム
塩又はマグネシウム塩の形態で存在するボリウＤ：／酸
に属する多糖類（Ｄ−マシヌ０ン酸とＬ−タル０ン酸と
から構成される）であり、通常上記ｍｓ類より希アルカ
リ液で抽出後ナトリウム塩として精製される。該アル４
：ｉ＃ナトリウムは、従来より医薬品分野においてその
使用が認められている通り、低毒性で安全性の保証され
たものである。また上記アルイン酸水溶性塩類の平均分
子量は、通常約６万〜２５万の範囲にあるのが適当であ
る。この平均分子量は、アル４：Ｊｍ塩を０．１＃塩酸
に溶出し、オストワルド型粘度計を用いて流下秒速度を
測定し、極限粘度を算出することにより求められたもの
である。上記平均分子量を有するアルイン酸水溶性塩の
２１Ｆ／Ｖ％水溶液は、通常Ｂ型粘廖計（０−９−２，
２分、２０°Ｃ）による粘度が約５〜ｌ ５０Ｑシチボ
イズの範囲にあり、この粘度範囲のアルイン酸塩が本発
明に好適に用いられ、所期の効果を奏し得る。The compounded medicine of the present invention must contain water-soluble salts of Alf:/# together with its active ingredient compound, and based on this, the action of the active ingredient compound can be enhanced without reducing the original medicinal efficacy of the active ingredient compound. It can be significantly reduced or prevented. Examples of the water-soluble salts of alinic acid used here include storium salts, potassium salts, anthinium salts, and amine salts of alinic acid. The above-mentioned alinic acid is a polysaccharide belonging to the polysaccharide D:/acid (D-machinic acid and L - talonic acid), and is usually purified as a sodium salt after extraction with a dilute alkaline solution from the above MSs. The Al 4
:i# Sodium has low toxicity and guaranteed safety, as its use has been recognized in the pharmaceutical field. The average molecular weight of the water-soluble alinic acid salts is usually in the range of about 60,000 to 250,000. This average molecular weight was determined by eluting the Al4:Jm salt in 0.1# hydrochloric acid, measuring the flow rate in seconds using an Ostwald viscometer, and calculating the intrinsic viscosity. A 21F/V% aqueous solution of an alinic acid water-soluble salt having the above average molecular weight is usually prepared using a B-type viscometer (0-9-2,
The viscosity is in the range of about 5 to 150Q liters (2 minutes, 20 DEG C.), and an alinate having a viscosity within this range is suitably used in the present invention and can produce the desired effect.
また本発明において上記アルイン酸水溶性塩類を配合さ
れる医薬品有効成分化合物としては、副作用として消化
管障害を惹起されるものをいずれも使用できる。その代
表例としてはアスピリン、フェニルづタリク１インドメ
タシン１メフエナム酸・レセルピン・コ〒チリン等を例
示できる。In addition, in the present invention, as the active pharmaceutical ingredient compound to which the water-soluble alinic acid salts are blended, any compound that causes gastrointestinal disorders as a side effect can be used. Typical examples thereof include aspirin, phenylbutaric, indomethacin, mefenamic acid, reserpine, and cotiline.
本発明配合薬品におけるアル４：Ｊ酸水溶性塩類及び上
記有効成分化合物の配合量は、２等化合物の種類や得ら
れる医薬品の製剤形態、投与経路、投与方決等に応じて
適宜に決定される。通常アルイン酸水溶性塩類は水溶液
の形態で用いられるのが最も好ましく、この場合その水
溶性を考慮すれば、濃度を約２〜Ｉ ０１Ｆ／Ｖ％、好
ましくは約３〜８１Ｆ／Ｖ％とするのがよい。この濃度
範囲の水溶液は通常ＰＨ７前後の範囲にあり、実用上好
ましいものであるが所望に応じて通常のｐＨ調節剤例え
ば水着化ナトリウムや塩酸等を用いてｐＨＨ節を行なう
こともできる。従って使用されるアルイン酸塩は、その
全カルボ＋シル基が中和（１００％中和）されている必
要はなく、約５０％以上が中和されていればよく、特に
実用上有利な−Ｈ６〜８の範囲とするためには、中和度
約７０％以上とするのが好ましい。上記において有効成
分化合物は、好ましくは、アル４：ｉｍｍ水性性塩類水
溶液に溶解させるか又は分散乃至懸濁させるのがよく、
特に上記分散乃至懸濁に際してはアル４：ｉｍ水溶性＃
１ｔＩＩ自体懸濁化剤としても作用するため、他に何ら
懸濁化剤等を利用せずとも利用に適したＭ濁液が春易に
得られる。上記有効成分化合物の配合量は、これらが通
常用いられる一般的形態における配合量と同様でよく、
一般には上記水溶液形線の場合的０．０１ Ｗ／Ｖ％以
上好ましくはＱ、 ９５ Ｗ／Ｖ％程魔以ヒの濃度とす
ればよい。有効成分化合物として例えばアスピリンを用
いる場合、服用に適したｌ単位形態当りに該化合物が約
０．５〜１．５１含有されるようにするのが好ましく、
フェニルプタリシでは約５０〜２００岬、またインドメ
タシンでは約２５η前後夫々含有されるようにするのが
好ましい。特に本発明では２等有効成分化合物をかなり
多量投与されるように配合しても、該化合物による副作
用を顕著に軽減でき、安全且つ事゛効に利用できる利点
がある。The amounts of the Al 4:J acid water-soluble salts and the above-mentioned active ingredient compounds in the compounded drug of the present invention are appropriately determined depending on the type of the secondary compound, the formulation form of the obtained drug, the route of administration, the method of administration, etc. Ru. Generally, the water-soluble salts of alinic acid are most preferably used in the form of an aqueous solution, and in this case, considering its water solubility, the concentration is about 2 to 101 F/V%, preferably about 3 to 81 F/V%. It is better. An aqueous solution having a concentration in this range usually has a pH of around 7, which is preferable for practical purposes, but if desired, pH adjustment can be carried out using a conventional pH adjusting agent such as sodium chloride or hydrochloric acid. Therefore, the alinate used does not need to have all its carbo+syl groups neutralized (100% neutralized), but only about 50% or more, which is particularly advantageous for practical use. In order to maintain H6 to H8, the degree of neutralization is preferably about 70% or more. In the above, the active ingredient compound is preferably dissolved or dispersed or suspended in an aqueous Al4:imm aqueous salt solution,
In particular, when dispersing or suspending the above, Al 4:im water-soluble #
Since 1tII itself also acts as a suspending agent, an M suspension suitable for use can be easily obtained without using any other suspending agent. The amount of the active ingredient compound may be the same as the amount in the general form in which they are usually used,
In general, the concentration may be set to 0.01 W/V% or more, preferably Q, and about 95 W/V% or more in the case of the above-mentioned aqueous solution line. When using, for example, aspirin as the active ingredient compound, it is preferred that the compound is contained in an amount of about 0.5 to 1.51 per 1 unit form suitable for administration;
It is preferable that phenylptalis be contained in about 50 to 200 capes, and that indomethacin be contained in about 25 η. In particular, the present invention has the advantage that even if the second active ingredient compound is administered in a fairly large amount, the side effects caused by the compound can be significantly reduced, and it can be used safely and effectively.
明の配合医薬品は、一般には経口的に投与されるが、特
にこれに限定されず、その医薬品有効成分化合物が通常
適用される投与方法によることができる。また本発明の
配合医薬品は、ドライシロップ剤、散剤、細粒剤、顆粒
剤、錠剤等の固剤の形態に調製され、之等形即に応じた
投与経路により投与されてもよい。これら各形態への調
製は常法に従い実施でき、その際必要に応じて慣用され
る各種の製剤担体例えば賦形剤、希釈剤、充填剤、増量
剤、結合剤、崩壊剤、湿潤剤、表面活性剤、等張化剤、
溶解補助剤、緩衝化剤、無痛化剤等や着色剤、保存剤、
香料、甘味料等を添加できることも、公知のこの種医薬
品と同様である。The compounded pharmaceuticals of the present invention are generally administered orally, but the administration method is not particularly limited thereto, and can be administered by the administration method normally applied to the active pharmaceutical ingredient compound. Further, the compounded pharmaceutical of the present invention may be prepared in the form of a solid agent such as a dry syrup, powder, fine granule, granule, tablet, etc., and may be administered by an appropriate administration route. Preparation into each of these forms can be carried out according to conventional methods, and at that time, various commonly used pharmaceutical carriers such as excipients, diluents, fillers, extenders, binders, disintegrants, wetting agents, surface Active agents, tonicity agents,
Solubilizing agents, buffering agents, soothing agents, coloring agents, preservatives, etc.
Similar to known pharmaceuticals of this type, flavorings, sweeteners, etc. can be added.
かくして調製される本発明配合医薬品の投与量は、これ
を適用される患者の症状、年令、体重、性別等に応じて
、また配合医薬品の投与形態、投与経路等に応じて適宜
決定できるが、通常水性液形態で経口的に投与する場合
を例にとれば、患者１人１日１回当り該液剤の約５〜１
２０寓ｊ１好ましくは約２０〜Ｉ ００ ｍｌを投与す
るのがよい。この投与はまた一般に好ましくは１日数回
（３〜５回）行なうことができる。The dosage of the compounded drug of the present invention thus prepared can be determined as appropriate depending on the symptoms, age, weight, sex, etc. of the patient to whom it is applied, as well as the dosage form and route of administration of the compounded drug. For example, when administered orally in the form of an aqueous liquid, approximately 5 to 1 of the liquid is administered per patient once a day.
Approximately 20 to 100 ml is preferably administered. This administration may also generally be carried out several times (3 to 5 times) per day.
本発明の配合医薬品は、これに含有される有効成分化合
物の本来の薬効を期して各種疾病の予防及び治療に有効
なものである。The compounded medicine of the present invention is effective in preventing and treating various diseases in view of the original medicinal effects of the active ingredient compounds contained therein.
以下本発明医薬品の処方例を挙げる。Examples of prescriptions for the pharmaceuticals of the present invention are listed below.
処方例１
アルイン酸ナトリウムＣ平均分子量約１６万、以下同じ
）の５０ｆを精製水１１に溶かし、これに微粉砕したア
スピリン２０Ｆを加えてホ七三十す−で分散させ、水性
液剤形態の本発明配合医薬品（解熱鎮痛剤）を得る。こ
れは１６患者１人１回当りその約５０ｍ服用させるのに
適している。Formulation Example 1 Dissolve 50F of sodium alinate C (average molecular weight approximately 160,000, the same shall apply hereinafter) in 11 parts of purified water, add finely ground aspirin 20F to this, and disperse with a hot water bath to prepare an aqueous solution. Obtain an invented combination drug (antipyretic analgesic). This is suitable for administering approximately 50 m of the drug per 16 patients.
処方例２
アル甲シ階ナトリウムを微粉砕し、その２５１に、微粉
砕したアスピリン１０Ｆを加えてよく混和し、瓶に充填
してドライシロップ剤形態の本発明配合医薬品【解熱鎮
痛剤）を得る。これは用崎その３．５ｇを精製水５０−
に混合してよく振り服用するのに適している。Prescription Example 2 Sodium alkoshichia is finely ground, and finely ground aspirin 10F is added to the resulting 251, mixed well, and filled into a bottle to obtain the combination drug of the present invention (antipyretic analgesic) in the form of a dry syrup. This is 3.5g of Yosaki and 50g of purified water.
It is suitable for mixing and shaking well.
処方例３
アル４：Ｊｍナトリウム末５１に、微粉末フェニルブタ
リン０．４ｆを加えて均一に混和し、瓶に充填してドラ
イシロップ剤形態の本発明配合医薬品（抗炎症剤）を得
る。これは用崎精輌水１００ｓＪに混合振盪して１回当
りその５０１ｄを１日２＠分服するのに適している。Formulation Example 3 Al 4: 0.4 f of finely powdered phenylbutaline is added to Jm sodium powder 51 and mixed uniformly, and the mixture is filled into a bottle to obtain a combination pharmaceutical of the present invention (anti-inflammatory agent) in the form of a dry syrup. This is suitable for mixing with 100 sJ of Yozaki Seisei Water and shaking and administering 501 d of the mixture at a time, 2 times a day.
処方例令
アルｆン醸すトリウム末２．５ｆに、微粉末イシドメタ
シン２５岬をよく混和し、瓶に充填してドライシロップ
剤形態の本発明配合医薬品（抗炎症剤）を得る。これは
用崎に精製水５０ｓ／に混金振優して分散させ、服用す
るのに適している。Prescription Example 2.5 f of thorium powder brewed in Alfon is thoroughly mixed with 25 caps of finely powdered isidomethacin, and the mixture is filled into a bottle to obtain the combination drug of the present invention (anti-inflammatory agent) in the form of a dry syrup. This is suitable for use by shaking the mixture in 50 seconds of purified water and dispersing it.
以下本発明配合医薬品につき行なった試験例を挙げる。Examples of tests conducted on the compounded pharmaceuticals of the present invention are listed below.
く血小板凝集に対する１試験〉
出血が起った時、まず血液中の血小板が粘着、凝集、変
態して、血小板血栓をつくり、−次止血が行なわれる。A test for platelet aggregation When bleeding occurs, platelets in the blood first adhere, aggregate, and metamorphose to form a platelet thrombus, which then stops the bleeding.
従って胃病変での出血に対しては、血小板が重要な役割
をする。上記血小板の凝集は、ｆｉＨ５，９以下では起
らないと言われている（ Ｆ、ｔ’。Therefore, platelets play an important role in preventing bleeding from gastric lesions. It is said that the above platelet aggregation does not occur at fiH5.9 or lower (F, t').
ａｒｔｔｎ、ｚｔ、ａｔ、ｃｔｕｔｒａｔｎｔｚｒａｔ
ｏｙｙ、 Ｈ，３Ｂ−４３＜１９７８）〕。またアスピ
リンが存在するとＡＤＰ等による血小板凝集が起らない
ことも報告されている〔山中学、「血小板」第１３７頁
、科学評論社発行、１９７９年〕。しかしながら本発明
者らは、本発明配合医薬品における如くアル甲シー水溶
性塩類の存在下においては、上記低戸〃条件下でも、ま
たアスピリン存在下においても血小板の凝集が認められ
、止血が行なわれること即ちアスピリンによる消化管出
血に対して上記アルした。この試験は上記事実を明らか
にし、本発明配合医薬品がアスピリンの副作用（消化管
出血）を顕著に抑制することを明らかにするものである
。arttn, zt, at, ctutratntzrat
oyy, H, 3B-43 <1978)]. It has also been reported that platelet aggregation caused by ADP and the like does not occur in the presence of aspirin [Yamanaka Manabu, "Platelets", p. 137, published by Kagaku Hyoronsha, 1979]. However, the present inventors found that in the presence of water-soluble salts such as in the combination drug of the present invention, platelet aggregation was observed even under the above-mentioned low conditions and in the presence of aspirin, and hemostasis was achieved. In other words, the above-mentioned treatment was applied to gastrointestinal bleeding caused by aspirin. This test clarified the above facts and clarified that the combination drug of the present invention significantly suppresses the side effects of aspirin (gastrointestinal bleeding).
この試験は以下の方法により行なわれた。即ちクエン酸
加ラット血液を遠沈（ＩＩＯＧＸＩＯ分）して、多血小
板血ｌ！（ＰＲＰ）を得る。その０．２５−に０．０１
＃アスじリン０．０５−及び５修アル平シ酸ナトリウム
水溶液０．０５ｍを加え、ＰＲＰの凝集状膝を顕微鏡で
観察した。対照として上記アル平シ酸ナトリウム水溶液
に替え、生理食塩液を用い同一試験を繰返した。This test was conducted using the following method. That is, citrated rat blood was centrifuged (IIOGXIO) to obtain platelet-rich blood l! Obtain (PRP). its 0.25- to 0.01
#Asdirin 0.05- and 0.05 ml of aqueous solutions of 5-modified sodium perosinate were added, and the aggregated PRP knee was observed under a microscope. As a control, the same test was repeated using a physiological saline solution instead of the above sodium alphosinate aqueous solution.
上記試験の結果、アＬ４：ｉｆｍナトリウム水溶液使用
の場合、アスピリンが存在するにかかわらず血小板の凝
集は認められたが一１対照とする生理食塩液使用の場合
は、アスじリンの存在によ〉血小板の凝集は全く認めら
れなかった。As a result of the above test, platelet aggregation was observed when a L4:ifm sodium aqueous solution was used regardless of the presence of aspirin, but when a physiological saline solution was used as a control, platelet aggregation was observed due to the presence of asdirin. > No platelet aggregation was observed.
〈潰瘍に対する効果〉
この試験はアスじリン投与によシ惹起される消化管障害
（潰瘍発生）の−作用が、本発明配合医薬品によれば顕
著に抑制されることを明らかにするものである。本発明
医薬品としては、以下のものな用いた。<Effect on ulcers> This test reveals that the effects of gastrointestinal disorder (ulcer development) caused by asdirin administration are significantly suppressed by the combination drug of the present invention. . The following drugs were used as the pharmaceuticals of the present invention.
即ち処方例１に準じて調製された５％アシｆシ酸ナナト
リウム水溶液、アスじリンを４ Ｗ／Ｖ襲濃度となるよ
う分散ｌｌＩｍさせ、懸濁液形態の本発明配合医薬品を
得た。このものは安定で短時間放置によっては沈殿を認
め得す、また長期間放置した場合若干沈殿することもあ
ったが該沈殿は振とうによシ容易に再分散し、均一な１
１１１ｉｌｔ１１形態に戻すことができるものであった
。That is, a 5% sodium acetate aqueous solution prepared according to Formulation Example 1 and asdirin were dispersed at a concentration of 4 W/V to obtain a pharmaceutical composition of the present invention in the form of a suspension. This product is stable and can be observed to precipitate if left for a short time.Also, if left for a long time, some precipitation may occur, but the precipitate is easily redispersed by shaking and becomes a uniform powder.
It was possible to return to the 111ilt11 format.
上記でＩＩＩＩｉシた本発明配合医薬品の２．５ｓ／（
アスじリンとして２００ｑ／＃）をラットに５日間投与
し、次いで諒ラットを層殺し、胃を摘出し、大彎にそっ
て切開し、潰瘍係数を求めた。該係数は、実体−黴鏡（
倍率６．３倍）で潰瘍の長さくＷ）を測定することによ
り求めた。対照としてアスピリンを精製水に４Ｗ／Ｖ％
濃度となるように懸濁させ、その２．５ｍ（２００ＭＩ
／＃）を直ちに用い同一試験を繰返した。各群につき夫
々８匹のラットを試験して得られた結果を下記第１表に
示す６１１８１表
上記第１表より、有意差検定（Ｔ−検定）の結果、１％
危険率で明らかに両群間に有意差が認められ、本発明配
合医薬品の投与によれば、消化管障害の誘発（潰瘍形成
）が明らかに抑制されることが判る。2.5s/(
Asdilin (200 q/#) was administered to rats for 5 days, and then the rats were sacrificed, the stomach was removed, and an incision was made along the greater curvature to determine the ulcer index. The coefficient is the entity − mold mirror (
It was determined by measuring the ulcer length W) at a magnification of 6.3 times. As a control, aspirin was added to purified water at 4W/V%.
Suspend at a concentration of 2.5 m (200 MI
/#) was used immediately to repeat the same test. The results obtained by testing 8 rats in each group are shown in Table 1 below. From Table 1 above, the result of the significance test (T-test) was 1%.
There was clearly a significant difference in the risk ratio between the two groups, and it was found that the induction of gastrointestinal disorders (ulcer formation) was clearly suppressed by administration of the combination pharmaceutical of the present invention.
（以 上）(that's all)
Claims (1)
ｆシ酸の水溶性塩類を配合したことを特徴とする配合医
薬品。■ A combination drug characterized by adding water-soluble salts of acyic acid to a drug that causes gastrointestinal disorders as a side effect.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3694382A JPS58152821A (en) | 1982-03-08 | 1982-03-08 | Blended drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3694382A JPS58152821A (en) | 1982-03-08 | 1982-03-08 | Blended drug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS58152821A true JPS58152821A (en) | 1983-09-10 |
Family
ID=12483826
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3694382A Pending JPS58152821A (en) | 1982-03-08 | 1982-03-08 | Blended drug |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58152821A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5039073A (en) * | 1987-04-06 | 1991-08-13 | Cooper Tire & Rubber Company | Mount for controlling or isolating vibration |
| EP1104168A2 (en) | 1999-11-29 | 2001-05-30 | Xerox Corporation | Method and apparatus for managing job contention for system resources in an electronic reprographic system |
| US6570670B1 (en) | 1999-11-29 | 2003-05-27 | Xerox Corporation | Method and apparatus to enable job streaming for a set of commonly shared resources |
| US6651081B1 (en) | 1999-11-29 | 2003-11-18 | Xerox Corporation | Method and apparatus for processing a high priority resource request in a system using a set of shared resources |
| US6671065B1 (en) | 1999-11-29 | 2003-12-30 | Xerox Corporation | Method and apparatus to optimize transition of resources from a lower priority to a higher priority job |
| US6717690B1 (en) | 1999-11-29 | 2004-04-06 | Xerox Corporation | Method and apparatus for managing job contention for system resources in an electrographic reproduction system where images are multibanded |
| US6762857B1 (en) | 1999-11-29 | 2004-07-13 | Xerox Corporation | Method and apparatus to enable processing multiple capabilities for a sub-job when using a set of commonly shared resources |
-
1982
- 1982-03-08 JP JP3694382A patent/JPS58152821A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5039073A (en) * | 1987-04-06 | 1991-08-13 | Cooper Tire & Rubber Company | Mount for controlling or isolating vibration |
| EP1104168A2 (en) | 1999-11-29 | 2001-05-30 | Xerox Corporation | Method and apparatus for managing job contention for system resources in an electronic reprographic system |
| US6501559B1 (en) | 1999-11-29 | 2002-12-31 | Xerox Corporation | Method and apparatus for managing job contention for system resources in an electronic reprographic system |
| US6570670B1 (en) | 1999-11-29 | 2003-05-27 | Xerox Corporation | Method and apparatus to enable job streaming for a set of commonly shared resources |
| US6651081B1 (en) | 1999-11-29 | 2003-11-18 | Xerox Corporation | Method and apparatus for processing a high priority resource request in a system using a set of shared resources |
| US6671065B1 (en) | 1999-11-29 | 2003-12-30 | Xerox Corporation | Method and apparatus to optimize transition of resources from a lower priority to a higher priority job |
| US6717690B1 (en) | 1999-11-29 | 2004-04-06 | Xerox Corporation | Method and apparatus for managing job contention for system resources in an electrographic reproduction system where images are multibanded |
| US6762857B1 (en) | 1999-11-29 | 2004-07-13 | Xerox Corporation | Method and apparatus to enable processing multiple capabilities for a sub-job when using a set of commonly shared resources |
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