KR100473963B1 - An Aqueous Solution for Injection or Infusion of Quinolone Antibiotics - Google Patents

An Aqueous Solution for Injection or Infusion of Quinolone Antibiotics Download PDF

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KR100473963B1
KR100473963B1 KR10-1998-0055541A KR19980055541A KR100473963B1 KR 100473963 B1 KR100473963 B1 KR 100473963B1 KR 19980055541 A KR19980055541 A KR 19980055541A KR 100473963 B1 KR100473963 B1 KR 100473963B1
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injection
aqueous solution
mannitol
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KR20000040012A (en
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함태진
연규정
온윤성
김제학
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씨제이 주식회사
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

본 발명은 하기 화학식(I)로 표시되는 공지의 퀴놀론계 항균화합물인 1-사이클로프로필-6-플루오르-1,4-디하이드로-4-옥소-7-([1α ,5α ,6β ]6-아미노-1-메틸-3-아자바이사이클로[3.3.0]헵탄-3-일)-1,8-나프티리딘-3-카르복실산의 염산염을 안정화제로서 만니톨과 함께 함유하여 액체상태로 매우 안정하며 비경구적으로 투여 가능한 제약학적 수용액 제제에 관한 것이다:The present invention relates to 1-cyclopropyl-6-fluor-1,4-dihydro-4-oxo-7-([1α, 5α, 6β] 6-, which is a known quinolone antibacterial compound represented by the following general formula (I): Hydrochloride of amino-1-methyl-3-azabicyclo [3.3.0] heptan-3-yl) -1,8-naphthyridine-3-carboxylic acid with mannitol as a stabilizer in very liquid form A stable, parenterally administrable aqueous pharmaceutical formulation is provided:

Description

퀴놀론계 항균화합물의 주사 또는 주입용 수용액 제제{An Aqueous Solution for Injection or Infusion of Quinolone Antibiotics}Aqueous Solution for Injection or Infusion of Quinolone Antibiotics

본 발명은 하기 화학식(I)로 표시되는 공지의 퀴놀론계 항균화합물인 1-사이클로프로필-6-플루오르-1,4-디하이드로-4-옥소-7-([1α ,5α ,6β ]6-아미노-1-메틸-3-아자바이사이클로[3.3.0]헵탄-3-일)-1,8-나프티리딘-3-카르복실산을 함유한 주사 또는 주입용 수용액 제제에 관한 것이다:The present invention relates to 1-cyclopropyl-6-fluor-1,4-dihydro-4-oxo-7-([1α, 5α, 6β] 6-, which is a known quinolone antibacterial compound represented by the following general formula (I): Aqueous solution for injection or injection containing amino-1-methyl-3-azabicyclo [3.3.0] heptan-3-yl) -1,8-naphthyridine-3-carboxylic acid:

상기 화학식(I)로 표시되는 화합물은 그람양성균 및 그람음성균에 대하여 우수한 항균활성을 나타내며 특히 폐렴구균 및 내성균에 대하여 탁월한 항균력을 보이는 공지의 퀴놀론계 항균화합물로서 기존의 성공적으로 응용되고 있는 로메플록사신, 오플록사신, 시프로플록사신 등의 퀴놀론계 항균제보다 뛰어난 항균력을 나타낼 뿐만 아니라 생체내 이용율과 반감기 면에서도 우수한 양상을 나타낸다.The compound represented by the formula (I) has excellent antimicrobial activity against Gram-positive bacteria and Gram-negative bacteria, and particularly known quinolone-based antimicrobial compounds exhibiting excellent antimicrobial activity against pneumococci and resistant bacteria. In addition to exhibiting superior antibacterial activity to quinolone antibacterial agents such as ofloxacin, ciprofloxacin, and the like, they also show excellent aspects in terms of bioavailability and half-life.

미국특허 제5,591,766호는 상기 화학식(I)의 화합물의 경구용 약제학적 조성물 처방을 기술하고 있으며, 이 화합물은 경구적 투여에 의해 임상적으로 우수한 항균효과를 나타낼 수 있다. 그러나, 경구투여가 곤란하거나 불가능한 경우, 빠른 시간내에 원하는 혈중농도를 얻고자 하는 경우, 장기간에 걸쳐 특정한 혈중농도를 유지해야 할 경우, 소아, 허약한 환자 또는 의식이 없는 환자를 치료하는 등의 경우에는 주사 또는 정맥내 주입해야 할 필요성이 있어 화학식(I)의 화합물의 주사 또는 주입용 수용액 제제의 사용이 바람직하다.U.S. Patent 5,591,766 describes oral pharmaceutical composition formulations of the compounds of formula (I), which can exhibit clinically good antimicrobial effects by oral administration. However, if oral administration is difficult or impossible, in order to obtain a desired blood concentration in a short time, to maintain a specific blood concentration over a long period of time, to treat children, fragile patients or unconscious patients, etc. There is a need for injection or intravenous injection, so the use of aqueous formulations for injection or injection of the compound of formula (I) is preferred.

그러나 퀴놀론계 항균제는 일반적으로 물에 대한 용해도가 매우 낮기 때문에 수용액으로 제제화하는데 많은 어려움이 따르며 이 때문에 난용성인 퀴놀론계 화합물의 용해도를 높이기 위한 많은 연구가 이루어져왔다. 대한민국특허 제87-1958호는 퀴놀론계 화합물의 수용액을 만들기 위해 적합한 산으로 염산, 메탄설폰산, 초산, 프로피온산, 숙신산, 푸마르산 등을 기술하고 있으며, 대한민국특허 제89-2040호에서는 아스파라긴, 글루탐산, 글루콘산 등을 언급하고 있다. 또한 대한민국특허 제89-2240호에서는 수산화나트륨, 수산화칼륨, 에탄올아민, 라이신, N-메틸글루타민, 아르기닌 등의 염기를 사용하여 퀴놀론 화합물의 수용액을 만드는 방법을 설명하고 있다.However, since quinolone antibacterial agents are generally very low in solubility in water, it is difficult to formulate them into aqueous solutions. Therefore, many studies have been made to increase the solubility of poorly soluble quinolone compounds. Korean Patent No. 87-1958 describes hydrochloric acid, methanesulfonic acid, acetic acid, propionic acid, succinic acid, fumaric acid, etc. as suitable acids to make an aqueous solution of a quinolone compound, and Korean Patent No. 89-2040 describes asparagine, glutamic acid, Gluconic acid and the like. In addition, Korean Patent No. 89-2240 describes a method of making an aqueous solution of a quinolone compound using a base such as sodium hydroxide, potassium hydroxide, ethanolamine, lysine, N-methylglutamine, arginine, and the like.

상기 화학식(I)의 화합물 역시 일반적인 퀴놀론계 항균제들과 마찬가지로 물에 대한 용해도가 매우 낮으므로 주사 또는 주입용 수용액 제제로 제제화하는데 어려움이 있다. 한편, 미국특허 제5,563,149호에는 화학식(I)의 화합물을 포함한 퀴놀론계 항균화합물의 주사 또는 주입용 수용액 제제를 만들기 위해 글루콘산 락톤, 글루콘산, 말린산, 숙신산, 아스파르트산 또는 염산을 사용하는 방법이 설명되어 있다.Like general quinolone antibacterial agents, the compound of formula (I) also has a low solubility in water, making it difficult to formulate an aqueous solution for injection or infusion. On the other hand, U.S. Patent No. 5,563,149 discloses a method of using gluconate lactone, gluconic acid, dried acid, succinic acid, aspartic acid or hydrochloric acid to prepare an aqueous solution preparation for injection or injection of a quinolone antimicrobial compound comprising a compound of formula (I). This is explained.

그러나, 상기 방법은 화학식(I)로 표시되는 화합물의 물에 대한 용해도를 높일 수는 있지만, 수용액을 실내광선에 장기간 노출할 때에는 주황색 또는 갈색으로 착색되거나 침전이 생기거나 함량이 저하되는 등의 문제점이 있다.However, the above method can increase the solubility of the compound represented by the formula (I) in water, but when the aqueous solution is exposed to room light for a long time, it may be colored orange or brown, precipitated, or reduced in content. There is this.

일반적으로 주사 및 주입용 액상제제는 1)혈액과 근육조직 등에 유해하지 않은 pH에서 높은 수용성을 가져야 할 뿐 아니라, 2)통상적인 보관조건하에서 용액 상태로 보존하였을 때 침전, 착색 또는 분해가 일어나지 않는 안정성이 절실히 요구된다. 따라서 화학식(I)로 표시되는 화합물의 주사 또는 주입용 액상제제의 개발을 위해서는 치료를 위한 충분한 양의 활성화합물을 물에 녹일 수 있어야 할 뿐 아니라, 빛 또는 공기 중에서의 장기간 보관시 안정성을 확보할 수 있는 보다 개선된 방법이 절실히 요구된다. 그러나, 일반적으로 유기화합물은 열, 습도, 공기 및 빛 등에 불안정하며 특히 퀴놀론계 항균화합물은 수용액 상태로 조제하여 보관시 빛이나 공기 등에 의하여 주황색 또는 갈색으로 착색되거나 함량이 저하되는 등 안정성의 유지에 어려움이 있음이 널리 알려져 있다.In general, liquid preparations for injection and infusion should not only have high water solubility at pH that is not harmful to blood and muscle tissue, but 2) do not precipitate, color or decompose when stored in solution under normal storage conditions. Stability is desperately needed. Therefore, in order to develop a liquid formulation for injection or injection of a compound represented by the formula (I), not only a sufficient amount of the active compound for treatment should be dissolved in water, but also a long-term storage in light or air should be ensured. There is an urgent need for more improved ways of doing this. However, organic compounds are generally unstable in heat, humidity, air, and light. Especially, the quinolone antimicrobial compounds are prepared in an aqueous solution and stored in orange or brown color or reduced in content due to light or air. It is well known that there are difficulties.

이에, 본 발명자들은 화학식(I)로 표시되는 화합물의 용해도를 증가시키고 동시에 용액으로서 장기간 보존하여도 안정성이 우수한 수용액 제제를 만들기 위해 다각도로 연구 검토한 결과, 화학식(I)의 화합물을 염산염으로 만들어 용해도를 높일 수 있으며, 만니톨을 첨가제로 사용할 경우 높은 안정성을 확보할 수 있다는 놀라운 사실을 발견하게 되었다. 특히 만니톨을 안정화제로 첨가한 수용액은 일반적으로 항산화제로 잘 알려진 약제학적 첨가물인 소디움 메타비설파이트를 가한 수용액의 경우보다 우수한 안정성을 나타내었으며 가혹한 산화조건에서도 만니톨을 첨가함으로써 약물의 분해를 방지할 수 있음을 확인하여 액체상태로 장기간동안 매우 안정한 수용액 제제를 제조할 수 있었다.Accordingly, the present inventors have studied and studied from various angles to increase the solubility of the compound represented by the formula (I) and at the same time to make an aqueous solution formulation excellent in stability even after long-term storage as a solution. It has been found that the solubility can be increased, and that mannitol can be used as an additive to ensure high stability. In particular, the aqueous solution containing mannitol as a stabilizer showed better stability than the aqueous solution containing sodium metabisulfite, a pharmaceutical additive generally known as an antioxidant, and can prevent decomposition of drugs by adding mannitol even under severe oxidation conditions. It was confirmed that it was possible to prepare a very stable aqueous solution formulation for a long time in the liquid state.

본 발명은 하기 화학식(I)로 표시되는 화합물의 염산염과 만니톨을 함유함을 특징으로 하는 비경구용 수용액 제제를 제공한다:The present invention provides an aqueous solution preparation for parenteral use, comprising hydrochloride and mannitol of a compound represented by the following formula (I):

만니톨은 동물 또는 식물 등의 자연계에 널리 존재하며 대부분의 채소에서도 발견되는 당알콜로서 인체에 투여하였을 때 매우 안전하다. 따라서 만니톨은 현재 식품 또는 의약품의 첨가제로 널리 쓰이고 있는데 그 용도는 주로 감미제, 정제 또는 캅셀제의 부형제, 주사제의 등장화제, 동결건조제품의 부형제 등으로 국한되어 있다.Mannitol is widely found in the natural world such as animals or plants, and is found in most vegetables and is very safe when administered to the human body. Therefore, mannitol is widely used as an additive in food or medicine, and its use is mainly limited to sweeteners, excipients for tablets or capsules, tonicity agents for injections, and excipients for lyophilized products.

본 발명자들의 실험결과 기존의 산을 이용하여 용해도를 높인 화학식(I)로 표시되는 화합물의 수용액은 1000Lux 정도의 실내광선 하에서 3 내지 7일간 보관시 주황색 또는 갈색으로 착색되며 10% 내지 30%의 함량저하가 일어난다. 또한 공기중에 노출시켜 보관하면 침전이 생성되는 것도 관찰할 수 있어 이러한 수용액은 기밀한 용기에 반드시 차광 보관하여야만 함을 알 수 있었다. 그러나, 본 발명에 의한 제제는 1000Lux의 실내광선 하에 2개월 이상 장기보관 하여도 착색 및 침전이 일어나지 않았으며 함량의 저하도 관찰되지 않았다.As a result of the experiments of the present inventors, the aqueous solution of the compound represented by the formula (I) having increased solubility using an existing acid is colored orange or brown when stored for 3 to 7 days under 1000L room light and has a content of 10% to 30%. Degradation occurs. In addition, it can be observed that when exposed to air and stored in the precipitate, such an aqueous solution must be stored in an airtight container. However, the preparation according to the present invention did not occur coloring or precipitation even after long-term storage for more than two months under room light of 1000Lux and no decrease in content was observed.

또한, 이처럼 광선뿐만 아니라 주사제의 통상적인 멸균과정에 요구되는 고온 및 고압, 그리고 함량을 저하시키거나 침전을 발생시키는 중요한 원인인 산소에 대하여도 탁월한 안정화 효과를 나타냄을 실험을 통해 알 수 있었다.In addition, the experiment showed that not only the light but also the high temperature and high pressure required for the normal sterilization process of the injection, and the excellent stabilizing effect against oxygen, which is an important cause of lowering the content or causing precipitation.

본 발명에 의한 제제는 용액상태로 매우 안정하므로 통상의 주사 또는 주입용 수용액 제제로의 제제화 과정 또는 유통 및 사용과정에서의 공기나 빛, 고온에 대한 노출에 대해 매우 안정하다.The formulations according to the invention are very stable in solution and therefore very stable against exposure to air, light or high temperatures in the formulation or distribution and use of conventional aqueous solutions for injection or infusion.

또한, 본 발명에 의한 제제는 별다른 pH 조정제를 첨가하지 않고도 인체에 투여하기 적합한 pH를 가지며 장기간의 보존이나 가혹한 조건하에서 유의할 만한 pH의 변화가 관측되지 않는다.In addition, the preparations according to the present invention have a pH suitable for administration to the human body without the addition of a separate pH adjuster and no significant pH change is observed under prolonged storage or harsh conditions.

이러한 탁월한 장점들 때문에 본 발명에 의한 제제는 즉시 사용할 수 있는 주사 또는 주입할 수 있는 수용액 제제로 제제화 할 수 있으며 따라서 번거로운 혼합과정의 필요 없이 바로 사용이 가능하다. 또한, 미리 표준화된 농도로 혼합되어 있어 정확한 용량을 투여할 수 있으며 따로 혼합할 필요가 없으므로 조제에 소모되는 물품, 시간, 노동력을 절감시킬 수 있다.Because of these excellent advantages, the preparations according to the invention can be formulated into ready-to-use injectable or injectable aqueous solutions and can therefore be used directly without the need for cumbersome mixing processes. In addition, it can be mixed to a pre-standardized concentration, so that the correct dose can be administered and there is no need for mixing separately, thereby reducing the amount of time, labor and labor consumed in the preparation.

본 발명에 의한 제제는 화학식(I)로 표시되는 화합물의 염산염 0.01 내지 20w/v%와 만니톨 0.01 내지 20w/v%를 함유할 수 있으며 용매로 주사용수를 사용할 수 있다. 등장화를 겸한 만니톨의 농도는 5w/v%가 적당하다. 본 발명의 제제의 pH는 2.0 내지 7.0, 바람직하게는 3.0 내지 5.0이다.The preparation according to the present invention may contain 0.01 to 20 w / v% of hydrochloride and 0.01 to 20 w / v% of mannitol of the compound represented by formula (I), and water for injection may be used as a solvent. The concentration of mannitol serving as isotonicity is appropriate 5w / v%. The pH of the formulation of the present invention is 2.0 to 7.0, preferably 3.0 to 5.0.

본 발명의 제제는 주사나 주입용 외에 경구용 액제, 사용할 때 희석하여 사용하는 농축액 형태의 경구용 또는 비경구용 제제로서 사람이나 동물의 세균성 질환의 예방 또는 치료의 목적으로 사용이 가능하다.The preparations of the present invention can be used for the purpose of preventing or treating bacterial diseases of humans or animals as oral or parenteral preparations in the form of concentrated liquids which are diluted when used orally, in addition to injection or infusion.

본 발명의 제제화는 하기 실시예를 통해 예시될 것이다. 그러나, 이들 실시예는 단지 본 발명을 예시하는 것이며 본 발명을 한정하는 것으로 이해되어서는 아니된다.Formulations of the invention will be illustrated by the following examples. However, these examples are merely illustrative of the present invention and should not be understood as limiting the present invention.

실시예 1Example 1

화학식(I)로 표시되는 화합물의 염산염 200mg200 mg of hydrochloride of the compound represented by formula (I)

만니톨 5.0gMannitol 5.0 g

주사용수 100ml로 맞춘다.Adjust to 100ml of water for injection.

pH 4.2pH 4.2

실시예 2Example 2

화학식(I)로 표시되는 화합물의 염산염 400mg400 mg of hydrochloride of the compound represented by formula (I)

만니톨 4.8gMannitol 4.8 g

주사용수 100ml로 맞춘다.Adjust to 100ml of water for injection.

pH 측정 4.1pH measurement 4.1

실시예 3Example 3

화학식(I)로 표시되는 화합물의 염산염 50mg50 mg of hydrochloride of the compound represented by formula (I)

만니톨 15gMannitol 15g

주사용수 100ml로 맞춘다.Adjust to 100ml of water for injection.

pH 4.3pH 4.3

실시예 4Example 4

화학식(I)로 표시되는 화합물의 염산염 300mg300 mg of hydrochloride of the compound represented by formula (I)

만니톨 1.0gMannitol 1.0g

주사용수 100ml로 맞춘다.Adjust to 100ml of water for injection.

pH 측정 4.2pH measurement 4.2

실시예 5Example 5

화학식(I)로 표시되는 화합물의 염산염 750mg750 mg of hydrochloride of the compound represented by formula (I)

만니톨 0.1gMannitol 0.1 g

주사용수 100ml로 맞춘다.Adjust to 100ml of water for injection.

pH 측정 4.0pH measurement 4.0

실험예Experimental Example

만니톨의 안정화 효과에 관한 시험Test on stabilizing effect of mannitol

온도 및 산소의 가혹한 조건하에서 만니톨의 안정화 효과에 관한 시험을 다음과 같이 실시하였다. 화학식(I)로 표시되는 화합물의 염산염을 주사용수에 녹인 용액에 만니톨을 각각 0, 2, 5, 10, 15 w/v%의 농도가 되도록 가하여 녹였다. 여기에 강력한 산화제로서 과산화수소를 최종농도가 3% 또는 9%가 되도록 가하여 교반한 후 이 용액을 바이알에 주입하고 고무마개로 막은 다음 밀봉하였다. 이것을 121℃에서 15분간 고압증기멸균하고, 분해되지 않은 화학식(I)로 표시되는 화합물의 양을 고속액체크로마토그래피법으로 정량하였다. 이 실험에 의한 결과는 하기 표 1과 같다.A test on the stabilizing effect of mannitol under severe conditions of temperature and oxygen was conducted as follows. Manitol was dissolved in a solution of the compound represented by the formula (I) in water for injection so as to have a concentration of 0, 2, 5, 10 and 15 w / v%, respectively. Hydrogen peroxide was added to the final concentration of 3% or 9% as a strong oxidizing agent and stirred. The solution was then injected into a vial, sealed with a rubber stopper, and sealed. This was autoclaved at 121 ° C. for 15 minutes, and the amount of the compound represented by the formula (I), which was not decomposed, was quantified by high performance liquid chromatography. The results of this experiment are shown in Table 1 below.

[표 1]TABLE 1

가혹한 산화조건 하에서 고압증기 멸균(121℃, 15분)한 후의 화학식(I)로 표시되는 화합물의 잔여량(%)Residual amount (%) of compound represented by formula (I) after autoclaving (121 ° C, 15 minutes) under severe oxidizing conditions

상기의 실험결과를 통해 만니톨이 고온, 고압과 산화제가 존재하는 가혹한 조건하에서도 화학식(I)로 표시되는 화합물에 대해 뚜렷한 안정화효과가 있음을 확인할 수 있다.Through the above experimental results, it can be seen that mannitol has a clear stabilizing effect on the compound represented by the formula (I) even under the harsh conditions of high temperature, high pressure and oxidizing agent.

본 발명에 따른 제제는 고온, 고압과 산화제가 존재하는 가혹한 조건하에서 안정한 효과가 있다.The preparations according to the invention have a stable effect under high temperature, high pressure and harsh conditions in which oxidants are present.

Claims (5)

하기 화학식(I)로 표시되는 화합물의 염산염과 만니톨을 함유함을 특징으로 하는 비경구용 수용액 제제:A parenteral aqueous solution preparation comprising hydrochloride and mannitol of a compound represented by the following formula (I): 제1항에 있어서, 용매로서 주사용수를 함유함을 특징으로 하는 수용액 제제.The aqueous solution preparation according to claim 1, which contains water for injection as a solvent. 제1항에 있어서, 화학식(I)로 표시되는 화합물의 염산염을 0.01 내지 20w/v% 함유하고 만니톨을 0.01 내지 20w/v% 함유함을 특징으로 하는 수용액 제제.The aqueous solution preparation according to claim 1, which contains 0.01 to 20 w / v% of hydrochloride of the compound represented by formula (I) and 0.01 to 20 w / v% of mannitol. 제1항에 있어서, 주사 또는 주입용인 수용액 제제.The aqueous solution preparation according to claim 1 for injection or infusion. 제1항 내지 제4항 중 어느 항에 있어서, pH가 3.0 내지 5.0인 수용액 제제.The aqueous solution preparation according to any one of claims 1 to 4, wherein the pH is 3.0 to 5.0.
KR10-1998-0055541A 1998-12-14 1998-12-14 An Aqueous Solution for Injection or Infusion of Quinolone Antibiotics KR100473963B1 (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63174930A (en) * 1987-01-14 1988-07-19 Hokuriku Seiyaku Co Ltd Aqueous composition of quinolonecarboxylic acid
KR950006218A (en) * 1993-08-14 1995-03-20 카르스텔센, 리브쉐어 Valve drive device for internal combustion engine
KR950016751A (en) * 1993-12-22 1995-07-20 이승철 New injectable compositions of quinolone antimicrobials and methods for their preparation
KR960000223A (en) * 1994-06-08 1996-01-25 김정순 Aqueous solution containing novel pyridone carboxylic acid compound and preparation method thereof
KR970007919A (en) * 1995-07-31 1997-02-21 배순훈 Eject Control Method of Video Cassette Recorder
KR970009589A (en) * 1995-08-31 1997-03-27 성호정 Instant Potato Noodles

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63174930A (en) * 1987-01-14 1988-07-19 Hokuriku Seiyaku Co Ltd Aqueous composition of quinolonecarboxylic acid
KR950006218A (en) * 1993-08-14 1995-03-20 카르스텔센, 리브쉐어 Valve drive device for internal combustion engine
KR950016751A (en) * 1993-12-22 1995-07-20 이승철 New injectable compositions of quinolone antimicrobials and methods for their preparation
KR960000223A (en) * 1994-06-08 1996-01-25 김정순 Aqueous solution containing novel pyridone carboxylic acid compound and preparation method thereof
KR970007919A (en) * 1995-07-31 1997-02-21 배순훈 Eject Control Method of Video Cassette Recorder
KR970009589A (en) * 1995-08-31 1997-03-27 성호정 Instant Potato Noodles

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