JPH0818988B2 - Oral cefalosporin composition - Google Patents
Oral cefalosporin compositionInfo
- Publication number
- JPH0818988B2 JPH0818988B2 JP61311456A JP31145686A JPH0818988B2 JP H0818988 B2 JPH0818988 B2 JP H0818988B2 JP 61311456 A JP61311456 A JP 61311456A JP 31145686 A JP31145686 A JP 31145686A JP H0818988 B2 JPH0818988 B2 JP H0818988B2
- Authority
- JP
- Japan
- Prior art keywords
- hydrochloride
- composition
- oral
- present
- glutamic 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
Landscapes
- Cephalosporin Compounds (AREA)
- Medicinal Preparation (AREA)
- 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］ 本発明は経口用セファロスポリン組成物に関する。TECHNICAL FIELD The present invention relates to an oral cephalosporin composition.
さらに詳しくは、ピバロイルオキシメチル７β−
［（Ｚ）−２−（２−アミノチアゾール−４−イル）−
２−メトキシイミノアセトアミド］−３−［（５−メチ
ル−2H−テトラゾール−２−イル）メチル］−３−セフ
ェム−４−カルボキシレート（以下、Ｔ−2588と称す
る。）またはその塩酸塩およびグルタミン酸・塩酸塩を
含有し、炭素数２〜６の有機カルボン酸を含有しない経
口用セファロスポリン組成物に関する。More specifically, pivaloyloxymethyl 7β-
[(Z) -2- (2-aminothiazol-4-yl)-
2-methoxyiminoacetamido] -3-[(5-methyl-2H-tetrazol-2-yl) methyl] -3-cephem-4-carboxylate (hereinafter referred to as T-2588) or its hydrochloride and glutamic acid. The present invention relates to an oral cephalosporin composition containing a hydrochloride and not containing an organic carboxylic acid having 2 to 6 carbon atoms.
［従来の技術］ Ｔ−2588またはその塩酸塩はすみやかに消化管から吸
収され、かつ吸収後直ちに生体内酵素により４位カルボ
キシル基のエステルが加水分解され、対応する有機カル
ボン酸化合物、即ち、７β−［（Ｚ）−２−（２−アミ
ノチアゾール−４−イル）−２−メトキシイミノアセト
アミド］−３−［（５−メチル−2H−テトラゾール−２
−イル）メチル］−３−セフェム−４−カルボン酸（以
下、Ｔ−2525と称する。）が生成する。このＴ−2525
は、グラム陽性菌、グラム陰性菌に対し、幅広い抗菌ス
ペクトルを有する極めてすぐれた化合物である（特公昭
60−52755号）が、Ｔ−2588またはその塩酸塩とグルタ
ミン酸・塩酸塩を含有する経口用セファロスポリン組成
物は全く知られていない。[Prior Art] T-2588 or its hydrochloride is promptly absorbed from the digestive tract, and immediately after absorption, the ester of the carboxyl group at the 4-position is hydrolyzed by an in vivo enzyme to give a corresponding organic carboxylic acid compound, that is, 7β. -[(Z) -2- (2-aminothiazol-4-yl) -2-methoxyiminoacetamide] -3-[(5-methyl-2H-tetrazole-2
-Yl) methyl] -3-cephem-4-carboxylic acid (hereinafter referred to as T-2525) is produced. This T-2525
Is an excellent compound with a broad antibacterial spectrum against Gram-positive and Gram-negative bacteria
No. 60-52755), there is no known oral cephalosporin composition containing T-2588 or its hydrochloride and glutamic acid / hydrochloride.
［発明が解決しようとする問題点］ その後の研究により、Ｔ−2588またはその塩酸塩の経
口吸収は食事の影響を受け、特に絶食時は食後時に比べ
吸収率が低下することが明らかとなった［ケモセラピー
（CHEMOTHERAPY）、第34巻、Ｓ−２、第134頁〜149頁、
1986年］。[Problems to be Solved by the Invention] Subsequent studies have revealed that oral absorption of T-2588 or its hydrochloride is affected by food, and that the absorption rate is particularly low during fasting compared with after eating. [CHEMOTHERAPY, Volume 34, S-2, pp. 134-149,
1986].
［問題点を解決するための手段］ 本発明者らは、上記問題点を解決すべく鋭意研究を行
った結果、Ｔ−2588またはその塩酸塩とグルタミン酸・
塩酸塩を含有する経口用セファロスポリン組成物が絶食
時も食後時とほぼ同時に吸収を示すことを見出し、本発
明を完成した。[Means for Solving Problems] As a result of intensive studies to solve the above problems, the present inventors have found that T-2588 or its hydrochloride and glutamic acid
The present invention has been completed by finding that an oral cephalosporin composition containing a hydrochloride exhibits absorption at the time of fasting and at the same time as after eating.
すなわち、本発明は（Ａ）ピバロイルオキシメチル７
β−［（Ｚ）−２−（２−アミノチアゾール−４−イ
ル）−２−メトキシイミノアセトアミド］−３−［（５
−メチル−2H−テトラゾール−２−イル）メチル］−３
−セフェム−４−カルボキシレートまたはその塩酸塩お
よび（Ｂ）グルタミン酸・塩酸塩を含有し、（Ｃ）炭素
数２〜６の有機カルボン酸を含有しない経口用セファロ
スポリン組成物を提供するものである。That is, the present invention provides (A) pivaloyloxymethyl 7
β-[(Z) -2- (2-aminothiazol-4-yl) -2-methoxyiminoacetamide] -3-[(5
-Methyl-2H-tetrazol-2-yl) methyl] -3
To provide an oral cephalosporin composition containing cephem-4-carboxylate or a hydrochloride thereof and (B) glutamic acid / hydrochloride, and (C) not containing an organic carboxylic acid having 2 to 6 carbon atoms. is there.
なお、本発明組成物は、食事などを取ることのできな
い重症患者に対してもその効果が期待できる極めて有用
性の高いものである。The composition of the present invention is extremely useful because it can be expected to be effective even for severely ill patients who cannot eat.
以下、本発明を詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明の（Ｂ）成分として用いられるグルタミン酸・
塩酸塩としては、Ｌ−グルタミン酸・塩酸塩が好まし
い。Glutamic acid used as the component (B) of the present invention
As the hydrochloride, L-glutamic acid / hydrochloride is preferable.
グルタミン酸・塩酸塩の配合量は、通常、Ｔ−2588ま
たはその塩酸塩に対して0.8倍量以上、特に1.0〜1.5倍
重量が好ましい。The amount of glutamic acid / hydrochloride is usually 0.8 times or more, and particularly preferably 1.0 to 1.5 times the weight of T-2588 or its hydrochloride.
本発明組成物は、Ｔ−2588またはその塩酸塩とグルタ
ミン酸・塩酸塩を均一に混合することによって得ること
ができる。The composition of the present invention can be obtained by uniformly mixing T-2588 or its hydrochloride with glutamic acid / hydrochloride.
本願発明の経口用セファロスポリン組成物は、炭素数
２〜６の有機カルボン酸を含有しないものである。The oral cephalosporin composition of the present invention does not contain an organic carboxylic acid having 2 to 6 carbon atoms.
本発明組成物は、経口投与剤として通常知られている
錠剤、カプセル剤、顆粒剤、丸剤、細粒剤、散剤又はシ
ロップ剤などの剤形に製剤化して使用する、製剤化にあ
たっては、賦形剤、界面活性剤、増量剤、崩壊剤、滑沢
剤、および結合剤などの通常使用される添加剤を適宜加
えることもできる。The composition of the present invention is used by formulating into a dosage form such as tablets, capsules, granules, pills, fine granules, powders or syrups which are generally known as oral administration agents. Additives that are commonly used, such as excipients, surfactants, extenders, disintegrants, lubricants, and binders can also be added as appropriate.
また、本発明組成物の投与方法、投与量および投与回
数は患者の症状に応じて適宜選択することができ、通常
成人に対しては経口投与によりＴ−2525換算100〜1200m
g/日を１〜数回に分割して投与すればよい。In addition, the administration method, dose and frequency of administration of the composition of the present invention can be appropriately selected according to the symptoms of the patient, and normally, for adults, oral administration gives T-2525 conversion of 100 to 1200 m.
The g / day may be divided into 1 to several times for administration.
［発明の効果］ つぎに、本発明組成物の経口投与による尿中回収率を
示す。[Effect of the Invention] Next, the urinary recovery rate by oral administration of the composition of the present invention is shown.
1.尿中回収率 実施例１および２の本発明組成物並びに参考例１およ
び２の経口用セファロスポリン組成物を人に絶食時およ
び食後30分に経口投与した場合のＴ−2525の０〜８時間
の尿中回収率を表−１に示す。1. Urinary Recovery Rate T-2525 of 0 when the composition of the present invention of Examples 1 and 2 and the oral cephalosporin composition of Reference Examples 1 and 2 are orally administered to a human at fasting and 30 minutes after eating. Table 1 shows the urinary recovery rates for 8 hours.
定量方法：高速液体クロマトグラフィー （HPLC）法 カラム：ヌクレオジル（Nucleosil）10C18 ［ケムコ社製］ 測定波長:254nm 移動相:1モル酢酸−酢酸ナトリウム緩衝液（pH5）100ml
およびアセトニトリル100mlに水を加え、1000mlとした
液 表−１から明らかなように、本発明組成物は絶食時、
食後時を問わず良好な吸収を示すものである。Quantitative method: High performance liquid chromatography (HPLC) method Column: Nucleosil 10 C 18 [Chemco] Measurement wavelength: 254 nm Mobile phase: 1 mol Acetic acid-sodium acetate buffer (pH 5) 100 ml
And 1000 ml of water by adding water to 100 ml of acetonitrile As is clear from Table 1, the composition of the present invention, when fasted,
It shows good absorption regardless of after meal.
［実施例］ 次に、本発明を実施例および参考例を挙げて説明する
が、本発明はこれに限定されるものではない。EXAMPLES Next, the present invention will be described with reference to examples and reference examples, but the present invention is not limited thereto.
実施例１ Ｔ−2588・塩酸塩26.3g、Ｌ−グルタミン酸・塩酸塩2
6.3g、コリドンCL［バスフ（BASF）社製］2.0g、アビセ
ルPH102（旭化成社製）6.44g、アドソリダ−101（無水
ケイ酸、フロイント社製）2.0g、ステアリン酸0.6gおよ
びステアリン酸マグネシウム1.2gを均一に混合し、常法
に従ってスラッグ打錠する。得られたスラッグ錠を粉砕
し、24メッシュスクリーンで篩過したのち、コリドンCL
2.0g、アドソリダ−101 4.0gおよびステアリン酸マグ
ネシウム1.2gを添加し、混合し、１錠当り720mg（Ｔ−2
525として200mg力価）に打錠する。Example 1 T-2588 / hydrochloride 26.3 g, L-glutamic acid / hydrochloride 2
6.3 g, Kollidon CL [manufactured by BASF] 2.0 g, Avicel PH102 (manufactured by Asahi Kasei) 6.44 g, Adsolida 101 (anhydrous silicic acid, manufactured by Freund) 2.0 g, stearic acid 0.6 g and magnesium stearate 1.2. g are uniformly mixed and slug tabletted according to a conventional method. The slug tablets obtained were crushed and sieved with a 24 mesh screen, and then Corydon CL
2.0 g, ADSOLIDA-101 4.0 g and magnesium stearate 1.2 g were added and mixed, and each tablet was 720 mg (T-2
525 to 200mg titer).
実施例２ Ｔ−2588・塩酸塩26.3g、Ｌ−グルタミン酸・塩酸塩3
9.4g、コリドンCL2.2g、アビセルPH102 6.58g、アドソ
リダ−101 3.60g、ステアリン酸0.66gおよびステアリ
ン酸マグネシウム1.32gを混合し、常法に従ってスラッ
グ打錠する。得られたスラッグ錠を粉砕し、24メッシュ
スクリーンで篩過したのちコリドンCL2.2g、アドソリダ
−101 6.58g、ステアリン酸マグネシウム1.32gを加
え、１錠896mg（Ｔ−2525として200mg力価）に打錠す
る。Example 2 T-2588 · hydrochloride 26.3 g, L-glutamic acid · hydrochloride 3
9.4 g, Kollidon CL 2.2 g, Avicel PH 102 6.58 g, Adsolida 101 3.60 g, stearic acid 0.66 g and magnesium stearate 1.32 g are mixed, and slug tabletted according to a conventional method. The slug tablets obtained were crushed and sieved with a 24 mesh screen, then 2.2 g of Kollidon CL, 6.58 g of Adsolida 101 and 1.32 g of magnesium stearate were added, and each tablet was 896 mg (titer of T-2525: 200 mg). Lock.
参考例１ Ｔ−2588 124g、乳糖11g、結晶セルロース8g、カル
ボキシメチルセルロースカルシウム10gおよびトウモロ
コシデンプン38.5gを混合し、これに４％ヒドロキシプ
ロピルメチルセルロース水溶液75mlを加えて湿式造粒を
行う。乾燥後、粉砕して24メッシュスクリーンにて篩過
し、カルボキシメチルセルロースカルシウム4gおよびス
テアリン酸マグネシウム1.5gを加え、１錠当り200mg
（Ｔ−2525として100mg力価）に打錠する。得られた錠
剤にヒドロキシプロピルメチルセルロース50g、ポリエ
チレングリコール6000 3g、酸化チタン7gおよび精製水
570gからなるフィルム液を用いて、常法に従い１錠当り
6mgのコーティングを行いフィルムコーティング錠とす
る。Reference Example 1 124 g of T-2588, 11 g of lactose, 8 g of crystalline cellulose, 10 g of calcium carboxymethyl cellulose and 38.5 g of corn starch are mixed, and 75 ml of a 4% hydroxypropylmethyl cellulose aqueous solution is added to this to perform wet granulation. After drying, crush and sieve with a 24 mesh screen, add carboxymethyl cellulose calcium 4g and magnesium stearate 1.5g, 200mg per tablet
Tablets (100 mg titer as T-2525). 50 g of hydroxypropylmethyl cellulose, 3 g of polyethylene glycol 6000, 7 g of titanium oxide and purified water were added to the obtained tablets.
Using 570 g of film solution, per tablet according to the usual method
Coat with 6 mg to give film-coated tablets.
参考例２ Ｔ−2588・塩酸塩140g、結晶セルロース10gおよびト
ウモロコシデンプン39gを混合し、10％コリドン30（バ
スフ社製）水溶液50mlにて湿式造粒を行う。乾燥後、粉
砕して24メッシュスクリーンにて篩過し、エーシー・デ
ィアイ・ソル［Ac−Di−Sol（旭化成社製）］30gおよび
ステアリン酸マグネシウム6gを加え、１錠当たり230mg
（Ｔ−2525として100mg力価）に打錠する。Reference Example 2 140 g of T-2588 / hydrochloride, 10 g of crystalline cellulose and 39 g of corn starch are mixed, and wet granulation is performed with 50 ml of 10% Kollidon 30 (manufactured by Basuf) aqueous solution. After drying, pulverize and sieve with a 24 mesh screen, add 30 g of AC DI Sol [Ac-Di-Sol (manufactured by Asahi Kasei)] and 6 g of magnesium stearate, and add 230 mg per tablet.
Tablets (100 mg titer as T-2525).
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭63−126824（ＪＰ，Ａ) 特開 昭60−146825（ＪＰ，Ａ) 特開 昭57−88126（ＪＰ，Ａ) 特公 昭60−52755（ＪＰ，Ｂ２) ─────────────────────────────────────────────────── --- Continuation of the front page (56) References JP-A-63-126824 (JP, A) JP-A-60-146825 (JP, A) JP-A-57-88126 (JP, A) JP-B-60- 52755 (JP, B2)
Claims (1)
［（Ｚ）−２−（２−アミノチアゾール−４−イル）−
２−メトキシイミノアセトアミド］−３−［（５−メチ
ル−2H−テトラゾール−２−イル）メチル］−３−セフ
ェム−４−カルボキシレートまたはその塩酸塩および
（Ｂ）グルタミン酸・塩酸塩を含有し、（Ｃ）炭素数２
〜６の有機カルボン酸を含有しない経口用セファロスポ
リン組成物。1. (A) Pivaloyloxymethyl 7β-
[(Z) -2- (2-aminothiazol-4-yl)-
2-methoxyiminoacetamido] -3-[(5-methyl-2H-tetrazol-2-yl) methyl] -3-cephem-4-carboxylate or a hydrochloride thereof and (B) glutamic acid / hydrochloride, (C) 2 carbon atoms
An oral cephalosporin composition containing no organic carboxylic acids of ~ 6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61311456A JPH0818988B2 (en) | 1986-12-27 | 1986-12-27 | Oral cefalosporin composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61311456A JPH0818988B2 (en) | 1986-12-27 | 1986-12-27 | Oral cefalosporin composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63165321A JPS63165321A (en) | 1988-07-08 |
| JPH0818988B2 true JPH0818988B2 (en) | 1996-02-28 |
Family
ID=18017437
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61311456A Expired - Lifetime JPH0818988B2 (en) | 1986-12-27 | 1986-12-27 | Oral cefalosporin composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0818988B2 (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5788126A (en) * | 1980-11-19 | 1982-06-01 | Kyoto Yakuhin Kogyo Kk | Agent for promoting peroral and transvaginal absorption and preparation containing the same |
| JPS6052755A (en) * | 1983-08-31 | 1985-03-26 | Matsushita Electric Works Ltd | Manufacture of gas-detecting element |
| JPS60146825A (en) * | 1984-01-10 | 1985-08-02 | Asahi Chem Ind Co Ltd | Oral drug pharmaceutical |
| JPH0818987B2 (en) * | 1986-11-17 | 1996-02-28 | 富山化学工業株式会社 | Oral cefalosporin composition |
-
1986
- 1986-12-27 JP JP61311456A patent/JPH0818988B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63165321A (en) | 1988-07-08 |
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