CN101683332B - high purity scutellarin salt bulk drug and preparation method thereof - Google Patents

Abstract

The invention relates to a new bulk drug in pharmaceuticals industry, and preparation process thereof. The bulk drug of the invention wherein has a weight percentage of more than 98% scutellarin salt. The preparation method is composed of following steps: first, using breviscapinun saled in market as raw materials, adding 5 to 10 times of water by weight, being heated to 60 to 80 DEG, adding 10 to 20 weight percentage of aqueous slkali until the pH value is 5 to 8; second, centrifugating the solution obtained in the step one and discarding the deposition, then the obtained solution going through macroporous resin column, washing and removing, discarding the deep brown part of the first eluant, and then collecting the yellow eluant part; third, the collected eluant is disposed in vacuum concentrator, concentrating until concentration of the scutellarin salt solution is 100 to 200 mg/ml; fourth, adding organic solvent to the concentrated solution obtained in the step three and stirring, depositing, standing and filtering; fifth, washing by using the same organic solvent of the step four for 3 to 6 times, drain, and drying at a temperature of 60 to 80 DEG, then the bulk drug is obtained.

Description

The high purity scutellarin salt bulk drug method for preparing

Technical field

The present invention relates to the crude drug in a kind of new pharmaceuticals industry, and preparation technology.

Background technology:

The Herba Erigerontis prime system is isolated flavonoids effective constituent from Herba Erigerontis Erigeron breviscapus (Vant) H-M herb, and main component is that lamp-dish flower acetic (has another name called scutellarin, scutellarin; Plain hereinafter to be referred as second); Chemical name is 4 ', 5,6-trihydroxyflavone-7-O-gluconic acid glycosides.Its commercially available breviscapine B raw material medicine second cellulose content is about 85-90%.Its various preparations have been widely used in the treatment cardiovascular and cerebrovascular disease clinically; Evident in efficacy; But its injection poor stability, period of storage is short, has phenomenons such as caloric response, skin pruritus, erythra to take place when individual patient is with the back clinically; The appearance of these phenomenons does not eliminate mainly due to crude drug due to the some of them impurity in process of production, and this problem fails over more than 30 year to solve since the Herba Erigerontis product comes out always.

The applicant has carried out research and the power of patenting to the high-purity scutellarin process for refining, and the patent No. is ZL200410079583.8.But what this patent was related is breviscapine B raw material medicine, and this crude drug can be used to prepare various Herba Erigerontis preparations.In the time will making the Herba Erigerontis ejection preparation, dissolve with alkali, could prepare.

The scutellarin salt bulk drug that directly is used to prepare ejection preparation does not also appear in the newspapers.

Summary of the invention

The objective of the invention is to overcome the deficiency of prior art, a kind of high purity scutellarin salt bulk drug that directly is used to prepare ejection preparation is provided.

The method for preparing of the high purity scutellarin salt bulk drug that another object of the present invention is to provide this.

The method for preparing of high purity scutellarin salt bulk drug of the present invention is made up of following steps:

One, is raw material with commercially available breviscapine, adds the water of 5-10 times of weight, be heated to 60-80 ℃; Make it dissolving; Adding percentage by weight is the aqueous slkali of 10-20%, to pH be 5-8, described aqueous slkali is sodium carbonate, sodium bicarbonate, arginine or lysine solution;

Two, with step () gained solution, adopt the centrifugal deposition of abandoning, gained solution through macroporous resin column, is used water elution again, discards eluent dark-brown part at first, regathers the yellow eluent part;

Three, the eluent of collecting is put in the vacuum concentrator, concentrating under reduced pressure under 60-80 ℃ of temperature conditions, the solution concentration that is concentrated into scutellarin salt is 100-200mg/ml;

Four, step (three) gained concentrated solution is added organic solvent and stir, deposition leaves standstill, and filters, and described organic solvent is acetone, ethanol or methanol, and addition is a concentrated solution: volume of organic solvent compares 1:3-10;

Five, use the organic solvent washing identical with step (four) 3-6 time, drain, 60-80 ℃ of drying promptly obtains high purity scutellarin salt bulk drug.

Can obtain high purity scutellarin salt bulk drug of the present invention through above step, wherein the content percentage by weight of scutellarin salt is greater than 98%.98% is a nil-norm, in fact, often will be higher than 99%, even higher.Can satisfy the needs of preparation ejection preparation fully.

Significance of the present invention is in pharmaceuticals industry, to provide a kind of new crude drug, and is the scutellarin salt bulk drug that is specifically designed to direct preparation ejection preparation.The appearance of this crude drug has been saved the original acidify essential in order to obtain high-purity scutellarin, has been filtered, washed most acid, when joining injection, adds adjusting PH with base again then, steps such as dissolving.Not only provide cost savings, more help environmental protection.This crude drug also can be used for preparing oral formulations, like oral liquid.

In the method for the invention, breviscapine is used alkali dissolution under 60-80 ℃ temperature conditions, be particularly conducive to the dissolved speed of lamp-dish flower acetic and fully the degree; Adopt centrifugal treating, not only can remove many impurity, but also can improve refining filtering effect largely.Go up macroporous resin column again, make some be difficult to isolating similar chemical compound and be able to effective disengaging.To guarantee the high-purity of obtained crude drug.

The specific embodiment

Embodiment only is used for the present invention is done further description, and does not limit the present invention.

Embodiment 1:

Claim commercially available breviscapine crude drug 500g, add the water of 5 times of weight, be heated to 70 ℃, transfer pH to 7.5 to make dissolving fully with 20% sodium bicarbonate solution.Solution is through 16000r.p.m centrifugation, and the AB-8 macroporous resin column is used water elution on the gained centrifugal liquid, and flow velocity is the 200-300ml/ branch; The dark-brown that elder generation's eluting goes out partly discards, and continues to be collected into light yellow (desirable 2ml eluent adds hcl acidifying is not had muddiness), and the eluent of collection is at 70 ℃, and pressure is 0.05MPa; Be evaporated to 4500ml, add the acetone of 5 times of volumes, stir; Deposition left standstill sucking filtration 10 hours; With washing with acetone 6 times,, promptly get purity up to 99.75% lamp-dish flower acetic sodium raw materials medicine 65 ℃ of oven dry.

Gained lamp-dish flower acetic sodium raw materials medicine is through the high performance liquid chromatograph assay determination, and data are following:

Use the instrument type: liquid chromatograph gradient mode: constant current detector: ultraviolet instrumentation model: LC-10A wavelength (nm): 335 column temperatures (℃): 32 post models: Phenomenx model Prodigy (250 ^*4.6mm) 5u ODS3100R integration method: area normalization method

The analysis result table

Take by weighing breviscapine sodium 100g, add water for injection 5000ml, add 100g sodium acetate used as stabilizers, add injection mannitol 140g; Dissolving adds the injection water to 10000ml, and microporous filter membrane filters; Filtrating is pressed the 10mg/ml packing, and lyophilizing promptly gets injection lamp-dish flower acetic sodium salt lyophilized preparation; Through the storage of 1 year, investigate quality, be up to the standards.

Claims (1)

1. the method for preparing of a high purity scutellarin salt bulk drug is characterized in that being made up of following steps:

One, is raw material with commercially available breviscapine, adds the water of 5-10 times of weight, be heated to 60-80 ℃; Make it dissolving; Adding percentage by weight is the aqueous slkali of 10-20%, to pH be 5-8, described aqueous slkali is sodium carbonate, sodium bicarbonate, arginine or lysine solution;

Two, with step () gained solution, adopt the centrifugal deposition of abandoning, gained solution through macroporous resin column, is used water elution again, discards eluent dark-brown part at first, regathers the yellow eluent part;

Three, the eluent of collecting is put in the vacuum concentrator, concentrating under reduced pressure under 60-80 ℃ of temperature conditions, the solution concentration that is concentrated into scutellarin salt is 100-200mg/ml;

Four, step (three) gained concentrated solution is added organic solvent and stir, deposition leaves standstill, and filters, and described organic solvent is acetone, ethanol or methanol, and addition is a concentrated solution: volume of organic solvent is than 1: 3-10;

Five, use the organic solvent washing identical with step (four) 3-6 time, drain, 60-80 ℃ of drying promptly obtains high purity scutellarin salt bulk drug.