KR910000418B1 - Process for preparing sodium amoxacillin - Google Patents
Process for preparing sodium amoxacillin Download PDFInfo
- Publication number
- KR910000418B1 KR910000418B1 KR1019880015164A KR880015164A KR910000418B1 KR 910000418 B1 KR910000418 B1 KR 910000418B1 KR 1019880015164 A KR1019880015164 A KR 1019880015164A KR 880015164 A KR880015164 A KR 880015164A KR 910000418 B1 KR910000418 B1 KR 910000418B1
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- South Korea
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- amoxicillin
- sodium
- amx
- solution
- amoxacillin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/04—Preparation
- C07D499/14—Preparation of salts
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/21—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/44—Compounds with an amino radical acylated by carboxylic acids, attached in position 6
- C07D499/48—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical
- C07D499/58—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical
- C07D499/64—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical by nitrogen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
본 발명은 소디움아목시실린의 제조방법 및 그 제조과정에 쓰이는 용액과 본 제조방법에 의한 소디움아목시실린에 관한 것이다.The present invention relates to a method for producing sodium amoxicillin, a solution used in the production process and sodium amoxicillin according to the present method.
이미 공개된 소디움아목시실린 제조방법은 수득율이나 페니실라닉산 및 그 다이머 또는 폴리머에 의한 혼탁등으로 순도도 저조할 뿐만 아니라 용해도에 종종 문제가 되어 왔었다. 이는 베타-락탐(β-lactam)항생제가 수용액상에서 오래경과되면 중합반응(polymerization)이 쉽게 일어나기 때문이다. 특히 동결건조시켜 제조하는 방법은 대량생산이 어려울뿐만 아니라 장시간 동안 낮은 온도를 유지해야 하므로 비경제적이며, 상당량의 불순물이 존재한다는 사실이 밝혀져 있다.(Farmaco, Ed. Prat. 1980, 35(2), 100-6(Eng). 참고) 이러한 문제점을 해결하기 위한 여러시도가 있었다. 예를 들면 일본특허공개 소 58-29915호에는 소디움아목시시린의 제조방법으로 소디움목시실린의 최초농도를 8-16%로 하고 입구온도 155-200℃로 하고 이를 출구온도 95-100℃에서 분무건조시키는 방법이 개시되어 있다. 특허공고 제88-1410호에는 수용성 t-부타놀의 소디움아목시실린용액을 입구온도 약 180℃ 및 출구온도 약 120℃에서 분무하는 것을 특징으로 하는 소디움아목시실린을 제조하는 방법이 개시되어 있다.Sodium amoxicillin production methods that have already been disclosed have often been problematic in terms of solubility as well as poor purity due to yield or turbidity by penicilanic acid and its dimers or polymers. This is because the polymerization easily occurs when beta-lactam antibiotics are long passed in aqueous solution. In particular, lyophilization is not only difficult to mass-produce, but also has to be kept at a low temperature for an extended period of time, making it uneconomical and having significant amounts of impurities present (Farmaco, Ed. Prat. 1980, 35 (2)). , 100-6 (Eng).) Several attempts have been made to solve this problem. For example, Japanese Patent Application Laid-Open No. 58-29915 describes a method for producing sodium amoxicillin, wherein the initial concentration of sodium moxicillin is 8-16%, the inlet temperature is 155-200 ° C, and the outlet temperature is 95-100 ° C. A method of spray drying is disclosed. Patent Publication No. 88-1410 discloses a method for producing sodium amoxicillin, which is sprayed with a sodium amoxicillin solution of water-soluble t-butanol at an inlet temperature of about 180 ° C and an outlet temperature of about 120 ° C.
본 발명자들은 비점이 비교적 높은 n-프로필알콜을 물과의 혼합용매로 사용하여, 입구온도를 높이면, 제조되는 소디움아목시실린이 미세분말화되고 중합이 거의 일어나지 않는 우수한 성질을 발견하여 본 발명을 완성하게 되었다. 따라서 본 발명의 목적은 새로운 혼합 용매를 사용하여 소디움아목시실린을 제조하는 신규방법을 제공하는 것이다. 다음에 본 발명을 상세히 설명한다.The present inventors use n-propyl alcohol having a relatively high boiling point as a mixed solvent with water, and when the inlet temperature is increased, the sodium amoxicillin produced is finely powdered and polymerization is found to have excellent properties that hardly occur. It became. It is therefore an object of the present invention to provide a novel process for preparing sodium amoxicillin using a fresh mixed solvent. Next, the present invention will be described in detail.
본 발명에 의하면 소디움아목시실린의 n-프로필알콜 수용액을 분무건조시켜서 고형의 소디움아목시실린을 얻는다. 소디움아목시실린의 용액중의 함량은 적어도 5%, 바람직하게는 25%까지 함유하면 바람직한 결과를 얻는다. 소디움아목시실린의 용액중의 함량은 적어도 5%, 바람직하게는 25%까지 함유하면 바람직한 결과를 얻는다. 이 용액을 그 건조기내로의 주입속도를 조절함으로서 원하는 입자도를 얻을 수 있다. 사용되는 아목시실린은 아목시실린삼수화물이 적당하며, 염기로는 수산화나트륨 수용액이 양호하다. 수산화나트륨은 약 10%의 과잉량을 넣는데 투명한 용액이 얻어질때까지 국부적인 pH변화가 일어나지 않도록 교반을 강하게 시켜 주면서 서서히 가하는데, 시간은 약 5-10분 정도면 적당하다. 최적반응은 아목시실린삼수화물 kg당 약 2.4리터의 증류수와 1.5리터의 노르말프로필알코올 수용액에 아목시실린삼수화물을 현탁시켜서 온도 22℃-27℃를 유지하며 가성소오다수용액을 가함으로써 이루어진다. 반응이 이루어진 후에는 중합반응(polymerization)이 일어나지 않도록 최단시간내에 10-20℃로 냉각하여, (통상은 15℃면 적당하다.) 여과한다. 분무건조에서는 입구온도 200℃-250℃, 출구온도 110℃-120℃로 하여 주입한다.According to the present invention, a solid sodium amoxicillin is obtained by spray-drying an aqueous n-propyl alcohol solution of sodium amoxicillin. A content of sodium amoxicillin in the solution at least 5%, preferably up to 25%, yields desirable results. A content of sodium amoxicillin in the solution at least 5%, preferably up to 25%, yields desirable results. The desired particle size can be obtained by controlling the injection rate of this solution into the dryer. Amoxicillin is preferably used amoxicillin trihydrate, the base is preferably a sodium hydroxide aqueous solution. Sodium hydroxide is added in an excess of about 10%. The solution is added slowly with strong agitation so that no local pH change occurs until a clear solution is obtained. The time is about 5-10 minutes. The optimum reaction is achieved by adding caustic soda aqueous solution by suspending amoxicillin trihydrate in about 2.4 liters of distilled water and 1.5 liters of normal propyl alcohol solution per kg of amoxicillin trihydrate. After the reaction is completed, the mixture is cooled to 10-20 DEG C in the shortest time so that polymerization does not occur (usually 15 DEG C is appropriate). In spray drying, injection is performed at an inlet temperature of 200 ° C-250 ° C and an outlet temperature of 110 ° C-120 ° C.
본 발명의 제조방법에 의하여 얻어진 소디움아목시실린은 제품의 질을 저하시키는 페니실로에어트나 다이머등의 불순물을 4.5%이상 함유하지 않는다. 또한 뛰어난 용해성 및 안전성을 지니며 건조시킨 후 최종의 수분함유율도 1..5%이하 보통은 0.9-1.2%정도밖에 함유하지 않아서 제품의 안전성을 지닐 수 있다. 제품에 함유된 소디움아목시실린은 무수아목시실린으로서 최소한 850mcg/mg의 역가를 지니고 있다.Sodium amoxicillin obtained by the production method of the present invention does not contain 4.5% or more of impurities such as penicillated air or dimer, which degrades the quality of the product. In addition, it has excellent solubility and safety, and the final water content after drying is less than 1..5%, and usually contains only 0.9-1.2%, so it can have the safety of the product. Sodium amoxicillin in the product is anhydrous amoxicillin with a titer of at least 850 mcg / mg.
본 발명을 실시예에 의해 상술하면 다음과 같다.Hereinafter, the present invention will be described in detail by way of examples.
[실시예]EXAMPLE
아목시실린삼수화물 200g을 증류수 480ml와 노프말프로필알코올 300ml의 혼합액에 현탁시켜서 22℃-27℃에서 8분간에 걸쳐 2N-수산화나트륨 수용액 254ml를 가해준 다음 바로 15℃로 급냉시키고 여과한다. 이 용액을 입구온도 230℃, 출구온도 115℃로 하여 분무건조하여 175g의 소디움아목시실린을 얻었다. 이 물질의 역가로 무수아목시실린으로서 853mcg/mg이었다.200 g of amoxicillin trihydrate was suspended in a mixed solution of 480 ml of distilled water and 300 ml of normal propyl alcohol, 254 ml of 2N aqueous sodium hydroxide solution was added at 22 ° C.-27 ° C. for 8 minutes, and then quenched to 15 ° C. and filtered. The solution was spray dried at an inlet temperature of 230 ° C. and an outlet temperature of 115 ° C. to obtain 175 g of sodium amoxicillin. The titer of this substance was 853 mcg / mg as anhydrous amoxicillin.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019880015164A KR910000418B1 (en) | 1988-11-17 | 1988-11-17 | Process for preparing sodium amoxacillin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019880015164A KR910000418B1 (en) | 1988-11-17 | 1988-11-17 | Process for preparing sodium amoxacillin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR900007851A KR900007851A (en) | 1990-06-02 |
| KR910000418B1 true KR910000418B1 (en) | 1991-01-25 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019880015164A KR910000418B1 (en) | 1988-11-17 | 1988-11-17 | Process for preparing sodium amoxacillin |
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| Country | Link |
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| KR (1) | KR910000418B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT412213B (en) * | 2000-05-30 | 2004-11-25 | Sandoz Ag | METHOD FOR DRYING AMOXICILLIN OR AMOXICILLIN-CONTAINING, ORAL, SOLID PHARMACEUTICAL COMPOSITIONS USING A GAS WITH A DEFINED GAS HUMIDITY |
-
1988
- 1988-11-17 KR KR1019880015164A patent/KR910000418B1/en not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT412213B (en) * | 2000-05-30 | 2004-11-25 | Sandoz Ag | METHOD FOR DRYING AMOXICILLIN OR AMOXICILLIN-CONTAINING, ORAL, SOLID PHARMACEUTICAL COMPOSITIONS USING A GAS WITH A DEFINED GAS HUMIDITY |
| US7807196B2 (en) | 2000-05-30 | 2010-10-05 | Sandoz Gmbh | Process for drying amoxicillin |
Also Published As
| Publication number | Publication date |
|---|---|
| KR900007851A (en) | 1990-06-02 |
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