JPH02124822A - Cephalosporin-containing composition for injection - Google Patents
Cephalosporin-containing composition for injectionInfo
- Publication number
- JPH02124822A JPH02124822A JP27810388A JP27810388A JPH02124822A JP H02124822 A JPH02124822 A JP H02124822A JP 27810388 A JP27810388 A JP 27810388A JP 27810388 A JP27810388 A JP 27810388A JP H02124822 A JPH02124822 A JP H02124822A
- Authority
- JP
- Japan
- Prior art keywords
- cephalosporin
- arginine
- lysine
- ornithine
- histidine
- 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
- 229930186147 Cephalosporin Natural products 0.000 title claims abstract description 29
- 229940124587 cephalosporin Drugs 0.000 title claims abstract description 29
- 150000001780 cephalosporins Chemical class 0.000 title claims abstract description 29
- 238000002347 injection Methods 0.000 title abstract description 9
- 239000007924 injection Substances 0.000 title abstract description 9
- 239000000203 mixture Substances 0.000 title abstract description 5
- 239000000654 additive Substances 0.000 claims abstract description 15
- 239000004475 Arginine Substances 0.000 claims abstract description 9
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims abstract description 9
- 230000000996 additive effect Effects 0.000 claims abstract description 9
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 9
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims abstract description 8
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims abstract description 8
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims abstract description 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000004472 Lysine Substances 0.000 claims abstract description 8
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims abstract description 8
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims abstract description 8
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229960003104 ornithine Drugs 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 claims abstract description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000004202 carbamide Substances 0.000 claims abstract description 6
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims abstract description 6
- 235000010234 sodium benzoate Nutrition 0.000 claims abstract description 6
- 239000004299 sodium benzoate Substances 0.000 claims abstract description 6
- 229960004025 sodium salicylate Drugs 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 4
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 8
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims description 8
- 229960002591 hydroxyproline Drugs 0.000 claims description 8
- 239000007972 injectable composition Substances 0.000 claims description 8
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 229960003885 sodium benzoate Drugs 0.000 claims description 4
- 229940045136 urea Drugs 0.000 claims description 4
- 150000003840 hydrochlorides Chemical class 0.000 claims description 3
- 231100000331 toxic Toxicity 0.000 claims 1
- 230000002588 toxic effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 4
- 238000002156 mixing Methods 0.000 abstract description 4
- 239000006172 buffering agent Substances 0.000 abstract description 2
- CRIZPXKICGBNKG-UHFFFAOYSA-N 3,7-dihydropurin-2-one Chemical compound OC1=NC=C2NC=NC2=N1 CRIZPXKICGBNKG-UHFFFAOYSA-N 0.000 abstract 1
- 239000004606 Fillers/Extenders Substances 0.000 abstract 1
- 239000007951 isotonicity adjuster Substances 0.000 abstract 1
- 239000000843 powder Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 5
- 229960003121 arginine Drugs 0.000 description 4
- 235000009697 arginine Nutrition 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229960002885 histidine Drugs 0.000 description 3
- 235000014304 histidine Nutrition 0.000 description 3
- 229960003646 lysine Drugs 0.000 description 3
- 235000018977 lysine Nutrition 0.000 description 3
- 238000011146 sterile filtration Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KWTQSFXGGICVPE-UHFFFAOYSA-N 2-amino-5-(diaminomethylideneamino)pentanoic acid;hydron;chloride Chemical compound Cl.OC(=O)C(N)CCCN=C(N)N KWTQSFXGGICVPE-UHFFFAOYSA-N 0.000 description 2
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- GGTYBZJRPHEQDG-WCCKRBBISA-N (2s)-2,5-diaminopentanoic acid hydrochloride Chemical compound Cl.NCCC[C@H](N)C(O)=O GGTYBZJRPHEQDG-WCCKRBBISA-N 0.000 description 1
- QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 150000001782 cephems Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、セファロスポリン含有注射用組成物に関する
もので、医薬の分野において有効に利用されるものであ
る。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an injectable composition containing a cephalosporin, which is effectively utilized in the pharmaceutical field.
〔従来の技術及び発明が解決しようとする課題１式（１
）
によって示されるセファロスポリン、即ち、７β−（２
−（５−アミノ−１，２，４−チアジアゾール−３−イ
ル）−（Ｚ）−２−フルオロメトキシイミノアセトアミ
ド）−３−（（Ｅ） −３−（（ＩＲ−力ルバモイル−
２−ヒドロキシエチル）ジメチルアンモニオ〕−１−プ
ロペン−１−イル〕３−セフェムー４−カルボキシレー
ト又はその非毒性塩（以下本発明に係るセファロスポリ
ンと呼ぶ）は、ダラム陽性菌からダラム陰性菌、嫌気性
菌まで広い抗菌スペクトルを有し、特に、耐性ブドウ球
菌、緑膿菌に対して強い抗菌力を示す有用性の高い第４
世代セフェム系抗生剤で、注射剤としての使用が期待さ
れる（特願昭６２−２７８３２６号）。[1 set of problems to be solved by the prior art and the invention (1
) is a cephalosporin represented by 7β-(2
-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamide)-3-((E) -3-((IR-rubamoyl-
2-Hydroxyethyl)dimethylammonio]-1-propen-1-yl]3-cephemu 4-carboxylate or its non-toxic salt (hereinafter referred to as the cephalosporin according to the present invention) can be used to detect Durum-positive bacteria to Durham-negative bacteria. It has a wide antibacterial spectrum, including bacteria and anaerobic bacteria, and has particularly strong antibacterial activity against resistant Staphylococcus and Pseudomonas aeruginosa.
This is a generation cephem antibiotic and is expected to be used as an injection (Japanese Patent Application No. 278326/1982).
しかし、本物質は化学的に不安定であり、水溶液中にお
いてはもちろん、乾燥粉末状態においても力価減退が観
察される。例えば、用時溶解型凍結乾燥注射剤の製造時
、特に、冷却過程で溶解性の低下に基づく凝集、不均一
化が生じ、用時溶解性が悪化するためセファロスポリン
注射剤として医療における実用化にあたって問題である
。However, this substance is chemically unstable, and a decrease in potency is observed not only in an aqueous solution but also in a dry powder state. For example, during the production of freeze-dried injections that dissolve before use, aggregation and non-uniformity occur due to decreased solubility, especially during the cooling process, which deteriorates the solubility before use. This is a problem when it comes to
従って、本発明の目的は医療において使用できるべく、
安定性、溶解性の高いセファロスポリン含有注射用組成
物を提供することにある。Therefore, the purpose of the present invention is to use the present invention in medical treatment.
An object of the present invention is to provide a cephalosporin-containing injectable composition with high stability and high solubility.
本発明者らは、本発明に係るセファロスポリンを用時溶
解粉末注射剤とした場合において、その安定性、溶解性
を高める注射用組成物として検討した。その結果、アル
ギニン、リジン、ヒスチジン、オルニチン、又はそれら
の塩酸塩、ヒドロキシプロリン、尿素、安息香酸ナトリ
ウム、サリチル酸ナトリウムを単独又は組み合わせて配
合することによって上記問題点が著しく改善されること
を見出し本発明を完成するに到った。The present inventors investigated an injectable composition that improves the stability and solubility of the cephalosporin according to the present invention when used as a powder injection that dissolves at the time of use. As a result, it was discovered that the above-mentioned problems can be significantly improved by blending arginine, lysine, histidine, ornithine, or their hydrochlorides, hydroxyproline, urea, sodium benzoate, and sodium salicylate alone or in combination.The present invention I have reached the point where I have completed the .
即ち、本発明は、前記式（１）で示されるセファロスポ
リン又はその非毒性塩に、アルギニン、リジン、ヒスチ
ジン、オルニチン、又はそれらの塩酸塩、ヒドロキシプ
ロリン、尿素、安息香酸ナトリウム、サリチル酸ナトリ
ウムの中から選ばれる添加剤を単独又は組み合わせて配
合してなることを特徴とするセファロスポリン含有注射
用組成物に係わるものである。That is, the present invention provides a method for adding arginine, lysine, histidine, ornithine, or a hydrochloride thereof, hydroxyproline, urea, sodium benzoate, or sodium salicylate to the cephalosporin represented by the formula (1) or a nontoxic salt thereof. This invention relates to a cephalosporin-containing injectable composition characterized by containing additives selected from among these, either singly or in combination.
以下、本発明の詳細な説明する。The present invention will be explained in detail below.
本発明の組成物中の上記添加剤の好ましい配合量は、上
記添加剤を単独配合する場合、本発明に係るセファロス
ポリン１重量部に対して０．５重量部以上が好ましい、
また上記添加剤を組み合わせて配合する場合、アルギニ
ン、リジン、ヒスチジン、オルニチン、又はそれらの塩
酸塩、ヒドロキシプロリンの中から選ばれる添加剤を組
み合わせて配合することが好ましく、これらの配合量は
それぞれ本発明に係るセファロスポリン１重量部に対し
０．２５重量部以上が好ましい。The preferred blending amount of the above additive in the composition of the present invention is preferably 0.5 parts by weight or more per 1 part by weight of the cephalosporin according to the present invention when the above additive is blended alone.
In addition, when blending the above additives in combination, it is preferable to blend additives selected from arginine, lysine, histidine, ornithine, their hydrochlorides, and hydroxyproline, and the amounts of these additives are determined according to the specifications. It is preferably 0.25 parts by weight or more per 1 part by weight of the cephalosporin according to the invention.
本発明の組成物の配合方法は、本発明に係るセファロス
ポリンと共に、上記必須成分の他に、医薬製剤の注射剤
製造において通常使用される補助成分、例えば増量剤、
緩衝化剤、等張化剤等を随意配合すればよい。The method of compounding the composition of the present invention includes, in addition to the above-mentioned essential ingredients, auxiliary ingredients commonly used in the manufacture of injections for pharmaceutical preparations, such as fillers, together with the cephalosporin according to the present invention.
A buffering agent, an isotonizing agent, etc. may be optionally added.
本発明の注射用組成物は主として、凍結乾燥粉末として
与えられる。例えば、本発明に係るセファロスポリンと
アルギニン又はその塩酸塩を注射用蒸留水に溶解し、ク
エン酸緩衝剤又は酸、アルカリで適当なｐＨに調整した
のち、無菌濾過し、一定量をバイアル又はアンプルに分
注し、凍結乾燥し、密栓又は密封する。また、無菌濾過
後、凍結乾燥して粉末とし、一定量をバイアル又はアン
プルに粉末充填してもよい。The injectable composition of the present invention is primarily provided as a lyophilized powder. For example, the cephalosporin and arginine or its hydrochloride according to the present invention are dissolved in distilled water for injection, adjusted to an appropriate pH with a citric acid buffer, acid, or alkali, filtered aseptically, and a certain amount is placed in a vial or Dispense into ampoules, lyophilize, and cap or seal. Alternatively, after sterile filtration, the product may be freeze-dried to form a powder, and a certain amount of the powder may be filled into vials or ampoules.
以下に記載する実施例によって本発明を更に詳細に説明
するが、本発明はこれらの実施例に限定されるものでは
ない。The present invention will be explained in more detail with reference to Examples described below, but the present invention is not limited to these Examples.
実施例１
本発明に係るセファロスポリン１０ｇ及びＬ−アルギニ
ン塩酸塩５ｇに予め用意したｐＨ４の６０ｍＭクエン酸
ナトリウム４０ｗＬ１を加えて溶解し、更にｐＨ４とな
るように微調整し、正確に全量を５０ａ＃とした。Example 1 10 g of cephalosporin according to the present invention and 5 g of L-arginine hydrochloride were added with 40 wL of 60 mM sodium citrate at pH 4 prepared in advance, dissolved, finely adjusted to pH 4, and the total amount was accurately adjusted to 50 a It was #.
この液を無菌濾過した後、１０−のバイアルに５１ずつ
分注し、凍結乾燥し、密栓した。After sterile filtration, this liquid was dispensed into 51 vials each, freeze-dried, and sealed tightly.
実施例２
本発明に係るセファロスポリン１０ｇ 、 Ｌ−リジン
塩酸塩２．５ｇ及びヒドロキシプロリン２．５ｇに予め
用意したｐＨ４の６０＋ｗＭクエン酸ナトリウム４０＠
ｌを加えて溶解し、更にｐＨ４に微調整し全量を正確に
５０−とじた。この液を無菌濾過した後、１０−のバイ
アルに５０−ずつ分注し、凍結乾燥し、密栓した。Example 2 10 g of cephalosporin according to the present invention, 2.5 g of L-lysine hydrochloride and 2.5 g of hydroxyproline were prepared in advance with 40@60+wM sodium citrate at pH 4.
1 was added to dissolve the solution, the pH was further finely adjusted to 4, and the total amount was adjusted to exactly 50%. After sterile filtration, this liquid was dispensed into 10-sized vials in 50-ml portions, freeze-dried, and hermetically sealed.
本発明に係るセファロスポリンを用時溶解粉末注射剤と
した場合における安定性及び用時溶解性を高める効果を
以下の実験例に示す。The following experimental example shows the effect of increasing the stability and solubility at the time of use when the cephalosporin according to the present invention is made into a ready-to-use powder injection.
実験例１
本発明に係るセファロスポリンを試験管に２００ａ＋ｇ
ずつとり、これにＬ−アルギニン塩酸塩、Ｌ−リジン塩
酸塩、Ｌ−ヒスチジン塩酸塩、し−ヒドロキシプロリン
、尿素、安息香酸ナトリウム、サリチル酸ナトリウム、
Ｌ−オルニチン塩酸塩をそれぞれ４０ｍｇ、１００ｍｇ
、２００ ｍｇ加え、ｐＨ４の６０１クエン酸緩衝液１
．６−を加えて溶解し、ｐＨ４に微調整し、全量を２−
とじた。Experimental Example 1 200a+g of cephalosporin according to the present invention was placed in a test tube.
To this, add L-arginine hydrochloride, L-lysine hydrochloride, L-histidine hydrochloride, hydroxyproline, urea, sodium benzoate, sodium salicylate,
40mg and 100mg of L-ornithine hydrochloride, respectively
, 200 mg, pH 4 601 citrate buffer 1
．． Add and dissolve 6-, finely adjust the pH to 4, and add 2-
Closed.
次に、メンブランフィルタ−で濾過し、２−のバイアル
に０．５−ずつ分注し、凍結乾燥し、密栓し、検体試料
とした。Next, the mixture was filtered with a membrane filter, dispensed into 2 vials in 0.5-unit portions, freeze-dried, and sealed tightly to serve as specimen samples.
別に、セファロスポリン２０Ｏｎ＋ｇをとり、６０ｍＭ
クエン酸緩衝液で溶解し、全量を２ｍ７とし、同様に、
メンブランフィルタ−で濾過し、０．５−ずつ分注し、
凍結乾燥し、密栓したものを対照試料とした。Separately, take cephalosporin 20On+g and 60mM
Dissolve with citrate buffer to make a total volume of 2 m7, and similarly,
Filter with a membrane filter, dispense into 0.5-unit portions,
A sample that was lyophilized and sealed was used as a control sample.
検体試料及び対照試料を５０°Ｃ１７日間保存し、溶解
性の確認と安定性を測定した。The test sample and control sample were stored at 50°C for 17 days, and solubility was confirmed and stability was measured.
即ち、溶解性については、各試料毎に０．５ ｍ７の注
射用蒸留水を加え、凍結乾燥粉末が溶解するか否かを確
認した。That is, regarding solubility, 0.5 m7 of distilled water for injection was added to each sample to check whether the freeze-dried powder would dissolve.
また、安定性については、各試料の残存率をフリーザー
（−３０℃）保存品を対照として下記の高速液体クロマ
トグラフィーの条件により内部標準物質とのピーク高比
により測定した。Regarding stability, the residual rate of each sample was measured by the peak height ratio with an internal standard substance under the following high performance liquid chromatography conditions using the sample stored in a freezer (-30°C) as a control.
高速液体クロマトグラフィー条件
固定相： ＹＭＣ−Ａ３０２０ＤＳ
移動相：メタノール：水：酢酸アンモニウム＝１００
： ９００ ： １
結果を表１に示す。High performance liquid chromatography conditions Stationary phase: YMC-A3020DS Mobile phase: Methanol: Water: Ammonium acetate = 100
: 900 : 1 The results are shown in Table 1.
（注） ＊１ 残存率：フリーザー品（ る残存率 ３０”Ｃ） に対す 寧２ 溶解性 （＋）：完全に溶解せず、不溶性物が認められる。(note) *1 Survival rate: Freezer product ( Survival rate 30”C) against Ning 2 solubility (+): Not completely dissolved, insoluble matter observed.
（−）二完全に溶解し、不溶性物が認められない。(-) Two completely dissolved and no insoluble matter was observed.
表１より、上記添加側を添加することにより、本発明に
係るセファロスポリンの溶解性、安定性が改善されるこ
とが明らかである。From Table 1, it is clear that the solubility and stability of the cephalosporin according to the present invention are improved by adding the above additive.
Claims (1)
−（５−アミノ−１，２，４−チアジアゾール−３−イ
ル）−（Ｚ）−２−フルオロメトキシイミノアセトアミ
ド〕−３−〔（Ｅ）−３−〔（１Ｒ−カルバモイル−２
−ヒドロキシエチル）ジメチルアンモニオ〕−１−プロ
ペン−１−イル〕−３−セフェム−４−カルボキシレー
ト、又はその非毒性塩に、アルギニン、リジン、ヒスチ
ジン、オルニチン、又はそれらの塩酸塩、ヒドロキシプ
ロリン、尿素、安息香酸ナトリウム、サリチル酸ナトリ
ウムの中から選ばれる添加剤を単独又は組み合わせて配
合してなることを特徴とするセファロスポリン含有注射
用組成物。 ２、アルギニン、リジン、ヒスチジン、オルニチン、又
はそれらの塩酸塩、ヒドロキシプロリン、尿素、安息香
酸ナトリウム、サリチル酸ナトリウムの中から選ばれる
添加剤を単独配合する場合、その配合量がセファロスポ
リン又はその非毒性塩１重量部に対し０．５重量部以上
である請求項１記載のセファロスポリン含有注射用組成
物。 ３、アルギニン、リジン、ヒスチジン、オルニチン、又
はそれらの塩酸塩、ヒドロキシプロリンの中から選ばれ
る添加剤を組み合わせて配合し、これらの配合量がそれ
ぞれセファロスポリン又はその非毒性塩１重量部に対し
０．２５重量部以上である請求項１記載のセファロスポ
リン含有注射用組成物。[Claims] 1. A cephalosporin represented by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼, that is, 7β-[2
-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamide]-3-[(E)-3-[(1R-carbamoyl-2
-Hydroxyethyl)dimethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate, or a non-toxic salt thereof, arginine, lysine, histidine, ornithine, or their hydrochloride, hydroxyproline 1. A cephalosporin-containing injectable composition comprising an additive selected from , urea, sodium benzoate, and sodium salicylate, either singly or in combination. 2. When an additive selected from arginine, lysine, histidine, ornithine, or their hydrochloride, hydroxyproline, urea, sodium benzoate, and sodium salicylate is blended alone, the amount of the additive selected from cephalosporin or its non-cephalosporin The cephalosporin-containing injectable composition according to claim 1, wherein the amount is 0.5 parts by weight or more per 1 part by weight of the toxic salt. 3. Additives selected from arginine, lysine, histidine, ornithine, or their hydrochlorides, and hydroxyproline are combined and blended in an amount of each of these additives per 1 part by weight of cephalosporin or its non-toxic salt. The cephalosporin-containing injectable composition according to claim 1, which contains 0.25 parts by weight or more.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP27810388A JPH02124822A (en) | 1988-11-02 | 1988-11-02 | Cephalosporin-containing composition for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP27810388A JPH02124822A (en) | 1988-11-02 | 1988-11-02 | Cephalosporin-containing composition for injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02124822A true JPH02124822A (en) | 1990-05-14 |
Family
ID=17592674
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP27810388A Pending JPH02124822A (en) | 1988-11-02 | 1988-11-02 | Cephalosporin-containing composition for injection |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02124822A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0695548A1 (en) * | 1994-08-03 | 1996-02-07 | Meiji Seika Kaisha Ltd. | A stably storable and readily water soluble composition of cephalosporin for injections |
| WO1997005862A3 (en) * | 1995-08-03 | 1997-04-17 | Sigma Tau Ind Farmaceuti | Use of basic amino acids and derivatives for lowering ceramide levels |
| DE102007002924A1 (en) | 2007-01-19 | 2008-07-24 | Bayer Healthcare Ag | ß-lactam-containing formulations with increased stability in aqueous solution |
| JP2010540448A (en) * | 2007-09-21 | 2010-12-24 | フォレスト・ラボラトリーズ・ホールディングス・リミテッド | Soluble preparation containing cephem derivative suitable for parenteral administration |
-
1988
- 1988-11-02 JP JP27810388A patent/JPH02124822A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0695548A1 (en) * | 1994-08-03 | 1996-02-07 | Meiji Seika Kaisha Ltd. | A stably storable and readily water soluble composition of cephalosporin for injections |
| WO1997005862A3 (en) * | 1995-08-03 | 1997-04-17 | Sigma Tau Ind Farmaceuti | Use of basic amino acids and derivatives for lowering ceramide levels |
| DE102007002924A1 (en) | 2007-01-19 | 2008-07-24 | Bayer Healthcare Ag | ß-lactam-containing formulations with increased stability in aqueous solution |
| JP2010540448A (en) * | 2007-09-21 | 2010-12-24 | フォレスト・ラボラトリーズ・ホールディングス・リミテッド | Soluble preparation containing cephem derivative suitable for parenteral administration |
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