WO2021097619A1 - 一种硫酸氨基葡萄糖氯化物复盐及其制备方法 - Google Patents
一种硫酸氨基葡萄糖氯化物复盐及其制备方法 Download PDFInfo
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- WO2021097619A1 WO2021097619A1 PCT/CN2019/119230 CN2019119230W WO2021097619A1 WO 2021097619 A1 WO2021097619 A1 WO 2021097619A1 CN 2019119230 W CN2019119230 W CN 2019119230W WO 2021097619 A1 WO2021097619 A1 WO 2021097619A1
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- double salt
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- glucosamine
- hydrochloride
- glucosamine sulfate
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/04—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen
- C07H5/06—Aminosugars
Definitions
- the invention relates to a double salt of glucosamine sulfate chloride and a preparation method thereof.
- the prepared product Due to the preparation method of the existing glucosamine sulfate chloride double salt, the prepared product has certain defects in product purity, structural stability, product quality, etc., and needs to be further improved.
- the purpose of the present invention is to provide a glucosamine sulfate hydrochloride double salt with stable structure and good quality and a preparation method thereof.
- a glucosamine sulfate chloride double salt which is characterized in that: X-ray diffraction of the double salt shows that it has the strongest peak at 27.1° ⁇ 0.2°, a DSC melting point of 204°C ⁇ 2°C, and a bulk density of 0.90-0.92.
- a preparation method of glucosamine sulfate chloride double salt which is characterized in that it comprises the following steps:
- the product is further post-treated to prepare a finished product of glucosamine sulfate chloride double salt.
- Step (1) In the dissolution reaction, first dissolve sulfuric acid at 80°C-95°C, and then cool to 55°C to dissolve glucosamine hydrochloride; or dissolve glucosamine hydrochloride and sulfate at 55°C and 80°C-95°C respectively .
- step (2) the molar ratio of glucosamine hydrochloride to sulfuric acid is 2.5:1, the reaction temperature is 50°C-65°C, and the reaction time is 0.5h-5h.
- step (3) the mass ratio of the added alcohol to the reaction solution of step (2) is 0.75:1, and the reaction is refluxed for 1h-5h at 50°C-60°C, then the reaction temperature is reduced to normal temperature, and the reaction time is 1h -5h.
- the post-treatment in step (4) includes filtration, washing and vacuum drying.
- the preparation process of the invention is simple, the cost is low, and the product purity is high (98%-102%). , The structure is stable, and the quality reaches the European and American Pharmacopoeia standards, which can be applied to industrialized and safe production.
- a preparation method of glucosamine sulfate chloride double salt including the following steps:
- the product is further post-treated to prepare a finished product of glucosamine sulfate chloride double salt.
- Step (1) In the dissolution reaction, first dissolve sulfuric acid at 80°C-95°C (for example, 80°C, 90°C, 95°C), and then cool to 55°C to dissolve glucosamine hydrochloride; or separate glucosamine hydrochloride and sulfate Dissolve at 55°C, 80°C-95°C (e.g. 80°C, 90°C, 95°C).
- 80°C-95°C for example, 80°C, 90°C, 95°C
- step (2) the molar ratio of glucosamine hydrochloride to sulfuric acid is 2.5:1, the reaction temperature is 50°C-65°C (for example, 50°C, 60°C, 65°C), and the reaction time is 0.5h-5h ( Example 0.5 h, 3 h, 5 h).
- step (3) the mass ratio of the added alcohol to the reaction solution of step (2) is 0.75:1, and the reaction is refluxed for 1h-5h under the conditions of 50°C-60°C (for example, 50°C, 60°C, 65°C) ( Example 1 h, 3 h, 5 h), then the reaction temperature is lowered to room temperature, and the reaction time is 1h-5h (example 1 h, 3 h, 5 h).
- the post-treatment in step (4) includes filtration, washing and vacuum drying.
- the product obtained X-ray diffraction shows that it has the strongest peak at 27.1° ⁇ 0.2°, the melting point of DSC is 204°C ⁇ 2°C, and the bulk density is 0.90-0.92. The purity of the product is 98%-102%.
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Abstract
硫酸氨基葡萄糖氯化物复盐及其制备方法,包括:(1)将盐酸氨基葡萄糖、硫酸物进行溶解反应;(2)盐酸氨基葡萄糖进一步与硫酸物进行离子交换反应;(3)逐步向步骤(2)的反应溶液中加入酒精,促进正反应;(4)将生成物进一步后处理,制备得到硫酸氨基葡萄糖氯化物复盐成品。所述复盐纯度高、结构稳定、质量达到欧美药典标准,适于产业化生产。
Description
本发明涉及一种硫酸氨基葡萄糖氯化物复盐及其制备方法。
现有的硫酸氨基葡萄糖氯化物复盐,由于其制备方法的原因,制得的产品在产品纯度、结构稳定型、产品质量等方面存在一定缺陷,需要进一步加以改进。
本发明的目的在于提供一种结构稳定,质量好的硫酸氨基葡萄糖氯化物复盐及其制备方法。
一种硫酸氨基葡萄糖氯化物复盐,其特征是:所述复盐的X衍射表明在27.1°±0.2°时具有最强峰,DSC 204℃±2℃熔融点,堆积密度0.90-0.92。
一种硫酸氨基葡萄糖氯化物复盐的制备方法,其特征是:包括下列步骤:
(1)将盐酸氨基葡萄糖、硫酸物进行溶解反应;
(2)盐酸氨基葡萄糖进一步与硫酸物进行离子交换反应;
(3)逐步向步骤(2)的反应溶液中加入酒精,促进正反应;
(4)将生成物进一步后处理,制备得到硫酸氨基葡萄糖氯化物复盐成品。
步骤(1)溶解反应中,先在80℃-95℃下溶解硫酸物,再降温到55℃溶解盐酸氨基葡萄糖;或将盐酸氨基葡萄糖、硫酸物分别在55℃、80℃-95℃下溶解。
步骤(2)中,盐酸氨基葡萄糖与硫酸物物质量的摩尔比为2.5:1,反应温度为50℃-65℃,反应时间为0.5h-5h。
步骤(3)中,加入的酒精与步骤(2)的反应溶液的质量比为0.75:1,在50℃-60℃条件下回流反应1h-5h,然后反应温度降低至常温,反应时间为1h-5h。
步骤(4)所述后处理为过滤、洗涤以及真空干燥。
本发明制备工艺简单、成本低廉、产品纯度高(98%-102%)。、结构稳定,质量达到欧美药典标准,可适用于产业化、安全化生产。
一种硫酸氨基葡萄糖氯化物复盐的制备方法,包括下列步骤:
(1)将盐酸氨基葡萄糖、硫酸物进行溶解反应;
(2)盐酸氨基葡萄糖进一步与硫酸物进行离子交换反应;
(3)逐步向步骤(2)的反应溶液中加入酒精,促进正反应;
(4)将生成物进一步后处理,制备得到硫酸氨基葡萄糖氯化物复盐成品。
步骤(1)溶解反应中,先在80℃-95℃(例80℃、90℃、95℃)下溶解硫酸物,再降温到55℃溶解盐酸氨基葡萄糖;或将盐酸氨基葡萄糖、硫酸物分别在55℃、80℃-95℃(例80℃、90℃、95℃)下溶解。
步骤(2)中,盐酸氨基葡萄糖与硫酸物物质量的摩尔比为2.5:1,反应温度为50℃-65℃(例50℃、60℃、65℃),反应时间为0.5h-5h(例0.5 h、3 h、5 h)。
步骤(3)中,加入的酒精与步骤(2)的反应溶液的质量比为0.75:1,在50℃-60℃(例50℃、60℃、65℃)条件下回流反应1h-5h(例1 h、3 h、5 h),然后反应温度降低至常温,反应时间为1h-5h(例1 h、3 h、5 h)。
步骤(4)所述后处理为过滤、洗涤以及真空干燥。
得到的产品:X衍射表明在27.1°±0.2°时具有最强峰,DSC 204℃±2℃熔融点,堆积密度0.90-0.92。产品纯度98%-102%。
Claims (6)
- 一种硫酸氨基葡萄糖氯化物复盐,其特征是:所述复盐的X衍射表明在27.1°±0.2°时具有最强峰,DSC 204℃±2℃熔融点,堆积密度0.90-0.92。
- 一种权利要求1所述的硫酸氨基葡萄糖氯化物复盐的制备方法,其特征是:包括下列步骤:(1)将盐酸氨基葡萄糖、硫酸物进行溶解反应;(2)盐酸氨基葡萄糖进一步与硫酸物进行离子交换反应;(3)逐步向步骤(2)的反应溶液中加入酒精,促进正反应;(4)将生成物进一步后处理,制备得到硫酸氨基葡萄糖氯化物复盐成品。
- 根据权利要求2所述的硫酸氨基葡萄糖氯化物复盐的制备方法,其特征是:步骤(1)溶解反应中,先在80℃-95℃下溶解硫酸物,再降温到55℃溶解盐酸氨基葡萄糖;或将盐酸氨基葡萄糖、硫酸物分别在55℃、80℃-95℃下溶解。
- 根据权利要求2所述的硫酸氨基葡萄糖氯化物复盐的制备方法,其特征是:步骤(2)中,盐酸氨基葡萄糖与硫酸物物质量的摩尔比为2.5:1,反应温度为50℃-65℃,反应时间为0.5h-5h。
- 根据权利要求2所述的硫酸氨基葡萄糖氯化物复盐的制备方法,其特征是:步骤(3)中,加入的酒精与步骤(2)的反应溶液的质量比为0.75:1,在50℃-60℃条件下回流反应1h-5h,然后反应温度降低至常温,反应时间为1h-5h。
- 根据权利要求2所述的硫酸氨基葡萄糖氯化物复盐的制备方法,其特征是:步骤(4)所述后处理为过滤、洗涤以及真空干燥。
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EP0214642A2 (en) * | 1985-09-09 | 1987-03-18 | Orion-Yhtymä Oy Fermion | Mixed salts of glucosamine sulphate and a process for the preparation of the same |
CN101012251A (zh) * | 2007-01-11 | 2007-08-08 | 庄建华 | 一种硫酸氨基葡萄糖复合盐的制备方法 |
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CN106749436A (zh) * | 2015-11-20 | 2017-05-31 | 广东先强药业有限公司 | 一种硫酸氨基葡萄糖氯化钠复盐的制备方法 |
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EP0214642A2 (en) * | 1985-09-09 | 1987-03-18 | Orion-Yhtymä Oy Fermion | Mixed salts of glucosamine sulphate and a process for the preparation of the same |
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