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Preparation method of palonosetron and palonosetron hydrochloride and injection

A technique for palonosetron and jone injections, applied in the field of injections, preparation of palonosetron hydrochloride, and palonosetron, can solve problems such as difficult product quality, high process requirements, and low product purity, and achieve Low cost, simple process and simple equipment

Active Publication Date: 2010-01-27
YANGTZE RIVER PHARM GRP SICHUAN HAIRONG PHARM CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, after the crude product prepared by this method is recrystallized, there are still many impurities in the product, and the purity of the finished product can only reach 99% after multiple recrystallizations, and the content of a single impurity is also more than 0.1%. If the quality of the product is to be further improved Very difficult
[0017] In summary, the existing preparation method of palonosetron hydrochloride has the problems of low product purity, high process requirements, high production cost, etc.

Method used

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  • Preparation method of palonosetron and palonosetron hydrochloride and injection
  • Preparation method of palonosetron and palonosetron hydrochloride and injection
  • Preparation method of palonosetron and palonosetron hydrochloride and injection

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Step 1, the synthesis of N-(1-aza-3(S)-bicyclo[2,2,2]octyl)-1,2,3,4-tetrahydronaphthalene-1S-carboxamide

[0051]

[0052] Put 300 g of 1,2,3,4-tetrahydro-1S-naphthoic acid into a 5 L reaction flask, add 3 L of freshly distilled toluene, stir until completely dissolved and the reaction solution is clear. Under ice-cooling conditions, 20ml of N,N-dimethylformamide was added dropwise. Keeping the temperature of the reaction system below 20°C, 0.56 L of thionyl chloride was slowly added dropwise, and the reaction was stirred at room temperature for 1 h after the dropwise addition was completed. Stirring was then continued at 50°C, and the reaction progress was tracked by TLC (developing solvent: petroleum ether: ethyl acetate = 3:1), and the reaction was complete after about 3 hours. Concentrate under reduced pressure to remove the solvent, add 0.5 L of freshly distilled toluene and continue to concentrate under reduced pressure until no solvent flows out, and add 0.5 ...

Embodiment 2

[0131] The preparation of embodiment 2 palonosetron hydrochloride injection

[0132] The raw material is: palonosetron hydrochloride 280mg (in C 19 h 24 N 2 O is 250mg), the auxiliary materials are mannitol 207.5g, sodium citrate 9.32g, citric acid 3.85g and edetate calcium sodium 2.5g, water for injection is added to 5000ml, made 1000, specification: 5ml: 0.25 mg (in C 19 h 24 N 2 O meter).

[0133] Weigh the sodium citrate, citric acid, mannitol and calcium sodium edetate of the above weight, add 2000ml of water for injection, stir and dissolve, then add medicinal activated carbon of 0.05% (W / V) of the total amount of the solution, and heat at 60°C Insulate and absorb for 15 minutes, filter and set aside.

[0134] Take by weighing the above-mentioned palonosetron hydrochloride in the water for injection of 1000ml, dissolve completely, set aside.

[0135] After mixing the above two solutions, add water for injection to make up to 5000ml, adjust the pH value to 4.5-5.5...

Embodiment 3

[0137] The pilot test of embodiment 3 palonosetron hydrochloride injection

[0138] Prepare three batches of pilot product according to the prescription of Table 7, each 10000, the yield is shown in Table 7.

[0139] Table 7 Proportion and yield of three batches of pilot test samples

[0140]

[0141] Table 8 lists the test results of the pilot test samples:

[0142] Table 8 Test results of three batches of samples

[0143]

[0144] It can be seen from the above table that the three batches (06040301, 06040501, 06040701) of samples prepared by the pilot test all meet the requirements.

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Abstract

The invention relates to a preparation method of palonosetron and palonosetron hydrochloride and an injection, which belongs to the pharmaceutical chemical field. The invention provides the preparation method of the palonosetron, and the preparation method comprises the steps of reacting (1-aza-3(S)-bicyclo [2,2,2] octane base)-(1,2,3,4-tetralin-1S-methyl) amine with Bis(trichloromethyl)carbonate, and adding boron trifluoride to perform the reflux reaction to obtain the palonosetron. The preparation method has the advantages of simple process as well as high yield, good purity and low cost of the obtained products.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and particularly relates to a preparation method of palonosetron, palonosetron hydrochloride and an injection. Background technique [0002] Palonosetron Hydrochloride (English name Palonosetron Hydrochloride, chemical name: (3aS)-2-[(S)-1-azacyclobis[2,2,2]oct-3-yl]-2,3, 3a, 4, 5, 6-hexahydro-1-one-1H benzo[a]isoquinoline hydrochloride) is a white crystalline powder with a melting point of >290°C and a molecular formula of C 19 h 24 N 2 O·HCl, molecular weight 332.9; easily soluble in water, soluble in propylene glycol, methanol and chloroform, slightly soluble in ethanol and 2-propanol. Palonosetron hydrochloride is a new type of 5-HT with high selectivity and high affinity 3 Receptor antagonist, clinically used for acute and delayed nausea and vomiting caused by moderate to severe emetogenic chemotherapy drugs. It acts competitively with 5-HT on 5-HT 3 receptor,...

Claims

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Application Information

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IPC IPC(8): C07D453/02A61K31/473A61K9/08A61K47/18A61K47/12A61K47/10A61P1/08
CPCY02P20/582
Inventor 薛立安李元波彭熙琳李丛菊袁瑜李方群黄敏
Owner YANGTZE RIVER PHARM GRP SICHUAN HAIRONG PHARM CO LTD
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