CN1679873A - Sarcadra injection, its making method and venous injection - Google Patents

Abstract

The invention relates to Sarcadra injection, its making method and venous injection. The medicine is obtained by following steps (1-1000 weight portion original medicine material): boiling, concentrating, adding clarifier, alcohol-settling, water-settling, hyperfiltration to get Sarcadra active component, subpackaging, disinfecting to get preparation, in which the fumaric acid is less than 30 mumg/m. The injection has the function of inflammation-relieving, vein relaxing, blood activating for treating pneumonia, appendicitis, cellulitis, rheumatalgia, injuries from falls and auxiliary therapeutic treatment for cancer. The invention avoids the medicine liquid thickness, deposition and color changing, stabilizes the preparation, prolongs the product effective date. The injection can be applied through vein so as to prevent the adverse effects such as pain in the administration location, blood stasis and even muscle necrosis.

Description

ZHONGJIEFENG ZHUSHEYE, its preparation method and intravenously administrable Glabrous Sarcandra Herb injection thereof

Invention field

The present invention relates to a kind of ZHONGJIEFENG ZHUSHEYE, its preparation method and intravenously administrable Glabrous Sarcandra Herb injection thereof belong to field of traditional Chinese.

Background technology

Glabrous Sarcandra Herb, another name sarcandra, Herba Pileae Scriptae, synthetism lotus are the complete stool of gold chestnut orchid Chloranthus glaber, perennial evergreen draft or undershrub, complete stool is used as medicine; Slightly warm in nature, bitter, suffering; Main component is volatile oil (bergamio etc. is arranged in the oil) butanedioic acid, fumaric acid, coumarone, glycosides displayed, lactone, tannic acid etc. Wherein volatile oil, butanedioic acid, fumaric acid, glycosides displayed etc. are antitumor active ingredient, complete stool has anti-inflammation, dispelling wind and removing obstruction in the meridians, the function of blood circulation promoting and dispersing pathogen accumulation, Diplococcus pneumopniae, gold look staphylococcus, Shigella shigae, Bao Shigella flexneri, typhoid bacillus, Escherichia coli, Pseudomonas aeruginosa there is stronger inhibitory action, be used for the treatment of the illnesss such as pneumonia, appendicitis, cellulitis, arthralgia due to wind-dampness, injury from falling down, and can be used for assistant treating cancer.

Existing ZHONGJIEFENG ZHUSHEYE production technology is seen the 14 WS3-B-2729-97[of ministry standard Traditional Chinese medicine historical preparation method for making] the middle content of describing; It prepares for glabrous sarcandra herb extract, be dark-brown supernatant liquid, can be clearing heat and detoxicating, dispersing swelling and dissipating binds, be used for the treatment of heat poison stop up contain due to pneumonia, appendicitis, cellulitis, bacillary dysentery, abscess, unite use with ZHONGJIEFENG PIAN, can treat the tumours such as digestive system cancer, cancer of pancreas, liver cancer. Be used for intramuscular injection. Because being pure Chinese medicinal preparation, be prone to liquid muddiness, precipitation, metachromatism in the preservation, affect product quality, the term of validity only is 2 years.

Utilization of the present invention adds fining agent, the ultrafiltration means are held back the macromolecular substances of protein, tannin, polysaccharide etc. in the injection extract, effectively removes invalid components, remains with effective substance, has guaranteed the curative effect of product, has increased the stability of product.

Because the existing method of administration of ZHONGJIEFENG ZHUSHEYE is intramuscular injection, use clinically inconvenience, patient's medicine-feeding part pain causes the bad reactions such as extravasated blood even muscular death easily.

But by the ZHONGJIEFENG ZHUSHEYE intravenously administrable of explained hereafter of the present invention, bioavilability is high, and easy to use, bad reaction is few. Comprising direct intravenous injection, infusion medium comprises glucose injection, sodium chloride injection etc.

Summary of the invention

The object of the present invention is to provide a kind of ZHONGJIEFENG ZHUSHEYE.

Another object of the present invention is to provide the preparation method of above-mentioned parenteral solution.

A further object of the present invention is to provide a kind of intravenously administrable Glabrous Sarcandra Herb injection of ZHONGJIEFENG ZHUSHEYE.

The present invention relates to a kind of ZHONGJIEFENG ZHUSHEYE, its preparation method and intravenously administrable Glabrous Sarcandra Herb injection thereof belong to field of traditional Chinese. The present invention by poach, concentrated, add fining agent, alcohol precipitation, depositing in water, ultrafiltration and obtain the Glabrous Sarcandra Herb active component, the preparation that makes through packing, sterilization. Injection of the present invention has anti-inflammation, dispelling wind and removing obstruction in the meridians, and the function of blood circulation promoting and dispersing pathogen accumulation is used for the treatment of the illnesss such as pneumonia, appendicitis, cellulitis, arthralgia due to wind-dampness, injury from falling down, and can be used for assistant treating cancer. Owing to adopt the preparation of advanced technologies treatment technology, obtain stable injection, effectively avoided liquid muddiness, precipitation, the metachromatism of appearance in the pure Chinese medicinal preparation preservation, make preparation stabilization, keeping life prolongs. Injection of the present invention can pass through the intravenous route administration, and bioavilability is high, and easy to use, bad reaction is few, avoids using clinically inconvenience, and patient's medicine-feeding part pain causes the bad reactions such as extravasated blood even muscular death easily.

Goal of the invention of the present invention can be achieved in the following manner:

A kind of ZHONGJIEFENG ZHUSHEYE, for the Glabrous Sarcandra Herb poach, concentrated, add fining agent clarification, alcohol precipitation and obtain Glabrous Sarcandra Herb active component preparation through post processing.

Wherein said post processing comprises that the liquid that alcohol precipitation is also concentrated is dissolved in water, refrigerates rear filtration, regulates PH, ultrafiltration, packing and sterilization.

Every milliliter of described ZHONGJIEFENG ZHUSHEYE contains fumaric acid and is no less than 30 μ g.

The invention still further relates to a kind of preparation method of ZHONGJIEFENG ZHUSHEYE, it is characterized in that with the Glabrous Sarcandra Herb poach, concentrated, add fining agent clarification, alcohol precipitation and obtain through post processing.

Described post processing comprises alcohol precipitation and concentrated liquid is added water, the rear filtration of refrigeration, regulates PH, ultrafiltration, packing and sterilization.

Specifically, the preparation method of ZHONGJIEFENG ZHUSHEYE of the present invention is:

(1) poach, concentrated: get Glabrous Sarcandra Herb 1-1000 weight portion, the water boiling that adds 3-8 times of weight decocts 2 times, and each 2-3 hour, filter, merge twice filtrate, concentrated;

(2) add the fining agent clarification: 0.03%～0.06% the fining agent that adds concentrate weight in the concentrate, be heated to 70～90 ℃, leave standstill, add again 0.015%～0.03% fining agent of concentrate weight, leave standstill rear centrifugally, get supernatant concentration;

(3) alcohol precipitation: slowly stir lower adding ethanol and carry out alcohol precipitation, filter after the 4-8 ℃ of refrigeration, filtrate recycling ethanol, and be concentrated into every milliliter of liquid and contain crude drug amount 3～4g, add ethanol, make to contain the alcohol amount for 80-85 %, filter after the 4-8 ℃ of refrigeration, filtrate recycling ethanol, concentrated filtrate to every milliliter of liquid contains crude drug amount 6～8g;

(4) post processing: with the water for injection of concentrate 1-3 times weight, refrigerate after 24 hours and filter, filtrate is regulated PH to 5.0-6.0 with the 10-20% sodium hydroxide solution, the active carbon of adding 1%, boil, filtration, centrifugal, ultrafiltration, add water for injection, filtration, use filtering with microporous membrane again, can is sterilized in ampoule and is made.

Wherein, after poach and the filtrate, filtrate is concentrated into every ml liquid and contains crude drug amount 1～2g. Add and liquid is concentrated into every ml liquid before the ethanol and contains crude drug amount 3～4g. Before the depositing in water, filtrate is concentrated into every ml liquid and contains crude drug amount 6～8g. After the ultrafiltration, adding water for injection extremely every ml contains fumaric acid 30～300 μ g; Centrifugal revolution is 4000 rev/mins; It is 100,000 ultrafiltration post that molecular cut off is selected in ultrafiltration.

Poach, the water for injection boiling that adds 3-8 times of weight of Glabrous Sarcandra Herb in concentrated decoct 2 times, and each 2-3 hour, filter, merge filtrate twice, and be concentrated into every ml liquid and contain crude drug amount 1～2g.

Add for the first time leave standstill 2 hours after fining agent and the heating after, leave standstill 4 hours for the first time after.

After adding ethanol under slowly stirring, 4-8 ℃ refrigerates 48 hours, filter, and filtrate recycling ethanol, and concentrated, add again ethanol, 4-8 ℃ refrigerates 48 hours, filters, and filtrate is refluxed in extractor, Recycled ethanol; Water for injection with concentrate 1-3 times weight.

The invention still further relates to intravenously administrable Glabrous Sarcandra Herb injection agent and preparation method thereof.

The suspended particulate of fining agent among the above-mentioned preparation method for only removing granularity the greater in the water extraction liquid and having precipitation trend, can keep effective polymer substance, thereby improve the fining agent of the stability of liquid, include but not limited to can be used in the prior art the various fining agents of Chinese medicine, such as commercially available 101 fruit juice clarifiers, chitin kind absorptive clarificant, the clarification of ZTC natural clarifying agent and fining agent B, fining agent A etc.

More particularly, ZHONGJIEFENG ZHUSHEYE of the present invention or intravenously administrable Glabrous Sarcandra Herb injection and preparation method thereof are: get Glabrous Sarcandra Herb 1-1000 weight portion, described weight portion can be the conventional units such as mg, g, kg, jin, two, money; The water for injection boiling that adds 3-8 times of weight of Glabrous Sarcandra Herb decocts 2 times, and each 2-3 hour, Filter paper filtering merged filtrate twice, and is concentrated into every ml liquid and contains crude drug amount 1～2g; 0.03%～0.06% the fining agent B that adds concentrate weight in the concentrate, be heated to 70～90 ℃, after leaving standstill 2 hours, 0.015%～0.03% the fining agent A that adds again concentrate weight, after leaving standstill 4 hours, centrifugal, supernatant inclines and, and is concentrated into every ml liquid and contains crude drug amount 3～4g; Slowly stir the lower ethanol that adds, add ethanol and make and contain the alcohol amount and be 70-75%, 4-8 ℃ of refrigeration 48 hours, Filter paper filtering, filtrate recycling ethanol, and be concentrated into every ml liquid and contain crude drug amount 3～4g, add ethanol, make the alcohol amount of containing be 80-85%, 4-8 ℃ of refrigeration 48 hours, Filter paper filtering, filtrate is refluxed in extractor, Recycled ethanol, concentrated filtrate, and be concentrated into every ml liquid and contain crude drug amount 6～8g; With the water for injection of concentrate 1-3 times weight, 4-8 ℃ refrigerates 24 hours, Filter paper filtering, filtrate is regulated PH to 5.0-6.0 with the 10-20% sodium hydroxide solution, adds 1% active carbon, boils 30 minutes, Filter paper filtering, centrifugal, ultrafiltration add water for injection, make every ml contain fumaric acid 30～300 μ g, filter, with the filtering with microporous membrane of 0.22 μ m, can is in ampoule, and 100 ℃ of sterilizations in 30 minutes make.

The resulting product specification is that 2ml/ props up, 5ml/ props up, 10ml/ props up, 20ml/ props up, and preferred 2ml/ props up, 5ml/ props up, 10ml/ props up, and every 1ml contains fumaric acid and is no less than 30 μ g, preferably contains fumaric acid 30～300 μ g/ml; Intramuscular injection, a 2ml-4ml, 2 times on the one; Drip-feed, 10ml-15ml on the one, or follow the doctor's advice.

In the preparation process, fining agent is for being purchased, and for making technique, constant product quality, fining agent B, fining agent A are provided by fixing manufacturer. Above-mentioned fining agent became clarification technique Co., Ltd in positive day available from Tianjin, and model has two kinds, is denoted as fining agent A, fining agent B.

Injection of the present invention adopts intravenous mode when using, bioavilability is high, and easy to use, bad reaction is few. Injection system can be: anti-inflammation: intramuscular injection, a 2～4ml, 1～2 time on the one; Drip-feed: a 4～12ml 1～2 time on the one, joins in 5%～10% glucose injection or 0.9% sodium chloride injection and uses.

Antitumor: intramuscular injection, a 3～4ml, 2 times on the one. Drip-feed: a 8～24ml 1～2 time on the one, joins in 5%～10% glucose injection or 0.9% sodium chloride injection and uses. Or follow the doctor's advice.

Parenteral solution of the present invention has following medicinal usage:

is clearing heat and detoxicating, dispersing swelling and dissipating binds;

be used for the treatment of heat poison stop up contain due to pneumonia, appendicitis, cellulitis, bacillary dysentery, abscess;

and ZHONGJIEFENG PIAN are united use, can treat the tumours such as digestive system cancer, cancer of pancreas, liver cancer.

Parenteral solution of the present invention has the phenomenons such as the degraded of effectively having avoided traditional injection to occur under the prerequisite of good drug effect, muddiness, precipitation, preparation stabilization, the term of validity that has prolonged ZHONGJIEFENG ZHUSHEYE in long term storage; With the intravenous route administration, bioavilability is high, and easy to use, bad reaction is few, avoids using clinically inconvenience, and patient's medicine-feeding part pain reduces and causes the bad reactions such as extravasated blood even muscular death.

The specific embodiment

Embodiment 1

Get Glabrous Sarcandra Herb 1000g, the water for injection boiling that adds 6 times of weight of Glabrous Sarcandra Herb decocts 2 times, and each 2 hours, Filter paper filtering merged filtrate twice, and concentrated every ml liquid contains crude drug amount 1g; Add 0.05% fining agent B of concentrate weight in the concentrate, be heated to 70～90 ℃, leave standstill 2 hours after, 0.025% the fining agent A that adds again concentrate weight, leave standstill 4 hours after, centrifugal, supernatant inclines and, and is concentrated into every ml liquid and contains crude drug amount 3g; Slowly stir the lower ethanol that adds, add ethanol and make that to contain the alcohol amount be 75%, 4-8 ℃ of refrigeration 48 hours, Filter paper filtering, filtrate recycling ethanol, and be concentrated into every ml liquid and contain crude drug amount 3g, add ethanol, make that to contain alcohol amount be 85%, 4-8 ℃ refrigerates 48 hours, Filter paper filtering, filtrate recycling ethanol, concentrated filtrate, and be concentrated into every ml liquid and contain crude drug amount 6g; With the water for injection of 3 times of weight of concentrate, 4-8 ℃ refrigerates 24 hours, Filter paper filtering, filtrate is regulated PH to 5.5 with 10% sodium hydroxide solution, adds 1% active carbon, boils 30 minutes, Filter paper filtering, centrifugal, ultrafiltration add water for injection, make every ml contain fumaric acid 30 μ g, filter, with the filtering with microporous membrane of 0.22 μ m, can is in ampoule, and 100 ℃ of sterilizations in 30 minutes make. The resulting product specification is that 2ml/ props up.

Embodiment 2

Get Glabrous Sarcandra Herb 2000g, the water for injection boiling that adds 8 times of weight of Glabrous Sarcandra Herb decocts 2 times, and each 3 hours, Filter paper filtering merged filtrate twice, and concentrated every ml liquid contains crude drug amount 1.5g; Add 0.04% fining agent B of concentrate weight in the concentrate, be heated to 70～90 ℃, leave standstill 2 hours after, 0.02% the fining agent A that adds again concentrate weight, leave standstill 4 hours after, centrifugal, supernatant inclines and, and is concentrated into every ml liquid and contains crude drug amount 4g; Slowly stir the lower ethanol that adds, add ethanol and make that to contain the alcohol amount be 70%, 4-8 ℃ of refrigeration 48 hours, Filter paper filtering, filtrate recycling ethanol, and be concentrated into every ml liquid and contain crude drug amount 4g, add ethanol, make that to contain alcohol amount be 80%, 4-8 ℃ refrigerates 48 hours, Filter paper filtering, filtrate recycling ethanol, concentrated filtrate, and be concentrated into every ml liquid and contain crude drug amount 8g; With the water for injection of 1 times of weight of concentrate, 4-8 ℃ refrigerates 24 hours, Filter paper filtering, filtrate is regulated PH to 5.0 with 20% sodium hydroxide solution, adds 1% active carbon, boils 30 minutes, Filter paper filtering, centrifugal, ultrafiltration add water for injection, make every ml contain fumaric acid 60 μ g, filter, with the filtering with microporous membrane of 0.22 μ m, can is in ampoule, and 100 ℃ of sterilizations in 30 minutes make. The resulting product specification is that 5ml/ props up.

Embodiment 3

Get Glabrous Sarcandra Herb 5000g, the water for injection boiling that adds 7 times of weight of Glabrous Sarcandra Herb decocts 2 times, and each 2.5 hours, Filter paper filtering merged filtrate twice, and concentrated every ml liquid contains crude drug amount 2g; Add 0.03% fining agent B of concentrate weight in the concentrate, be heated to 70～90 ℃, leave standstill 2 hours after, 0.015% the fining agent A that adds again concentrate weight, leave standstill 4 hours after, centrifugal, supernatant inclines and, and is concentrated into every ml liquid and contains crude drug amount 3.5g; Slowly stir the lower ethanol that adds, add ethanol and make that to contain the alcohol amount be 70%, 4-8 ℃ of refrigeration 48 hours, Filter paper filtering, filtrate recycling ethanol, and be concentrated into every ml liquid and contain crude drug amount 3g, add ethanol, make that to contain alcohol amount be 80%, 4-8 ℃ refrigerates 48 hours, Filter paper filtering, filtrate recycling ethanol, concentrated filtrate, and be concentrated into every ml liquid and contain crude drug amount 8g; With the water for injection of 2 times of weight of concentrate, 4-8 ℃ refrigerates 24 hours, Filter paper filtering, filtrate is regulated PH to 6.0 with 10% sodium hydroxide solution, adds 1% active carbon, boils 30 minutes, Filter paper filtering, centrifugal, ultrafiltration add water for injection, make every ml contain fumaric acid 120 μ g, filter, with the filtering with microporous membrane of 0.22 μ m, can is in ampoule, and 100 ℃ of sterilizations in 30 minutes make. The resulting product specification is that 2ml/ props up.

Embodiment 4

Get Glabrous Sarcandra Herb 10000g, the water for injection boiling that adds 6 times of weight of Glabrous Sarcandra Herb decocts 2 times, and each 2 hours, Filter paper filtering merged filtrate twice, and is concentrated into every ml liquid and contains crude drug amount 1g; Add 0.06% fining agent B of concentrate weight in the concentrate, be heated to 70～90 ℃, leave standstill 2 hours after, 0.03% the fining agent A that adds again concentrate weight, leave standstill 4 hours after, centrifugal, supernatant inclines and, and is concentrated into every ml liquid and contains crude drug amount 3g; Slowly stir the lower ethanol that adds, add ethanol and make that to contain the alcohol amount be 75%, 4-8 ℃ of refrigeration 48 hours, Filter paper filtering, filtrate recycling ethanol, and be concentrated into every ml liquid and contain crude drug amount 3g, add ethanol, make that to contain alcohol amount be 8 5%, 4-8 ℃ refrigerates 48 hours, Filter paper filtering, filtrate recycling ethanol, concentrated filtrate, and be concentrated into every ml liquid and contain crude drug amount 8g; With the water for injection of 2 times of weight of concentrate, 4-8 ℃ refrigerates 24 hours, Filter paper filtering, filtrate is regulated PH to 5.8 with 10% sodium hydroxide solution, adds 1% active carbon, boils 30 minutes, Filter paper filtering, centrifugal, ultrafiltration add water for injection, make every ml contain fumaric acid 150 μ g, filter, with the filtering with microporous membrane of 0.22 μ m, can is in ampoule, and 100 ℃ of sterilizations in 30 minutes make. The resulting product specification is that 2ml/ props up.

Embodiment 5

Get Glabrous Sarcandra Herb 4000g, the water for injection boiling that adds 7 times of weight of Glabrous Sarcandra Herb decocts 2 times, and each 3 hours, Filter paper filtering merged filtrate twice, and is concentrated into every ml liquid and contains crude drug amount 1.3g; Add 0.03% fining agent B of concentrate weight in the concentrate, be heated to 70～90 ℃, leave standstill 2 hours after, 0.015% the fining agent A that adds again concentrate weight, leave standstill 4 hours after, centrifugal, supernatant inclines and, and is concentrated into every ml liquid and contains crude drug amount 3.3g; Slowly stir the lower ethanol that adds, add ethanol and make that to contain the alcohol amount be 70 %, 4-8 ℃ of refrigeration 48 hours, Filter paper filtering, filtrate recycling ethanol, and be concentrated into every ml liquid and contain crude drug amount 3.3g, add ethanol, make that to contain alcohol amount be 80%, 4-8 ℃ refrigerates 48 hours, Filter paper filtering, filtrate recycling ethanol, concentrated filtrate, and be concentrated into every ml liquid and contain crude drug amount 7g; With the water for injection of 2.5 times of weight of concentrate, 4-8 ℃ refrigerates 24 hours, Filter paper filtering, filtrate is regulated PH to 5.2 with 10% sodium hydroxide solution, adds 1% active carbon, boils 30 minutes, Filter paper filtering, centrifugal, ultrafiltration add water for injection, make every ml contain fumaric acid 200 μ g, filter, with the filtering with microporous membrane of 0.22 μ m, can is in ampoule, and 100 ℃ of sterilizations in 30 minutes make. The resulting product specification is that 2ml/ props up.

Experimental example 1

This experimental example is the appearance character of injection embodiment 1 of the present invention, the inspection of pH value project, and check result is as follows:

PH value checks: get this product, an appendix VIIG checks that pH value is 5.0-6.0, and is up to specification according to Chinese Pharmacopoeia version in 2000.

Clarity test: check according to Chinese Pharmacopoeia version standard test in 2000 operational procedure " injection " check general rule, up to specification.

Proterties: injection of the present invention is fallow to dark-brown clear liquid.

Experimental example 2

This experimental example is the toxicity test parameter:

Heat-original determinating: in accordance with the law check (an appendix VIII of Chinese Pharmacopoeia version in 2000 A). Dosage is by the every kg injection of rabbit body weight this product 1ml, and conclusion is: this product is up to specification.

Undue toxicity: send out inspection according to two appendix XI of Chinese Pharmacopoeia version in 2000 C undue toxicity by intravenously administrable, this product is up to specification.

Long term toxicity is measured: the indexs such as successive administration observation in three months routine blood test, liver function, kidney merit are all normal, and the main organs pathologic finding is showed no unusually, toxic reaction do not occur.

Experimental example 3

This experimental example is the qualitative determination of parenteral solution embodiment 1 of the present invention.

Get this product 0.5ml and put in the test tube, add zinc powder and reach on a small quantity 1 of 0.1% ammonium chloride solution, low baking temperature is heated to dried. At the benzole soln wetting filter paper of test tube lid with 5% paradime thylaminobenzaldehyde-20% trichloroacetic acid, continue the low baking temperature heating, filter paper shows purple.

Get this product number droplet, put on filter paper, drying is observed aobvious light blue green fluorescence in that ultraviolet lamp (365nm) is lower. Behind ammonia fumigating, the displaing yellow spot, fluorescence strengthens.

Protein is got this product 1ml, adds 30% sulfosalicylic acid test solution 1ml of new preparation, mixes, and places 5 minutes, muddiness must not occur.

Oxalates is got this product 2ml, adds 2～3 of 3% calcium chloride test solutions, places 10 minutes, muddiness or precipitation must not occur.

Tannin is got this product 1ml, adds the physiological saline 5ml that contains 1% egg of new preparation, places 10 minutes, muddiness or precipitation must not occur.

Potassium ion is got this product 1ml, and evaporate to dryness burns to charing with little heated first, 500～600 ℃ of blazing extremely fully ashing, adds spirit of vinegar again

Make dissolving. Put in the 25ml measuring bottle, thin up is to scale, and mixing is as need testing solution. Get two of 10ml nessler colorimetric tubes, accurate adding standard potassium ion solution 0.8ml in the first pipe, add alkaline formaldehyde solution and (get formalin, with 0.1mol/L sodium hydroxide solution adjust pH to 8.0～9.0) 12 droplets, 2 of 3% EDTA sodium solutions, 3% sodium tetraphenylborate solution 0.5ml, thin up becomes 10ml, the accurate need testing solution 1ml that adds in the second pipe with the simultaneously in accordance with the law operation of first pipe, shakes up, first, second two pipes are with putting on the black paper, from up to down have an X-rayed, the turbidity that shows in the second pipe and first pipe relatively must not be denseer.

The preparation of standard potassium ion solution: it is an amount of to get potassium sulfate, and porphyrize is dried to constant weight in 110 ℃, and precision takes by weighing 2.330g, puts in the 1000ml measuring bottle, adds water and makes in right amount dissolving and be diluted to scale, shakes up, as stock solution. Before use, precision is measured stock solution 10ml, puts in the 100ml measuring bottle, and thin up shakes up to scale, namely gets (K that every ml is equivalent to 100 μ g)

Resin is got this product 5ml, adds 1 of hydrochloric acid, places 30 minutes, should separate out without floccule.

Heavy metal is got the residue of leaving under the residue on ignition item, checks (2000 editions one appendix IX E of Chinese Pharmacopoeia) must not cross 10/1000000ths in accordance with the law.

Arsenic salt is got this product 2ml, checks (2000 editions one appendix IX F of Chinese Pharmacopoeia) must not cross 5/1000000ths in accordance with the law.

Residue on ignition is got this product 10ml, puts in the crucible of ignition to constant weight, measures (2000 editions one appendix IX J of Chinese Pharmacopoeia) in accordance with the law, leaves over residue and must not cross 1.5% (g/ml).

Parenteral solution of the present invention is up to specification with the inspection of beginning a project.

Experimental example 4

This experimental example is the quantitative assay of parenteral solution embodiment 1 of the present invention.

The system suitability octadecylsilane chemically bonded silica is filler, and 0.16mol/L potassium dihydrogen phosphate (be 2.80 with phosphoric acid regulating ph value) is mobile phase, and the detection wavelength is 210nm; Number of theoretical plate is pressed fumaric acid and is calculated, and should be not less than 5000.

The preparation precision of reference substance solution takes by weighing the fumaric acid reference substance 10mg that is dried to constant weight through 105 ℃, put in the 25ml measuring bottle, the water dissolving also is diluted to scale, shake up, the accurate 2ml that draws puts in the 100ml measuring bottle, is diluted with water to scale, shake up, namely get (containing fumaric acid 8 μ g among every 1ml).

The accurate this product solution 5ml that draws of the preparation of need testing solution puts in the 25ml measuring bottle, and thin up shakes up to scale, and get final product.

Accurate reference substance solution and each 5～10 μ l of need testing solution of drawing of determination method, the injection liquid chromatography is measured, and be get final product.

By three batches of mensuration, the every ml of result contains fumaric acid and all is no less than 30 μ g.

Parenteral solution of the present invention through 4500LX illumination 10 days, 60 ℃ the heating 10 days after,, clarity is good, content results is stable, pH value is stable, illustrates that parenteral solution of the present invention is to light, thermally-stabilised.

Conclusion: parenteral solution of the present invention meets the injection quality requirement, without any toxic action, uses human-body safety, and the preparation stability test result is good.

Comparative example 1

The ZHONGJIEFENG ZHUSHEYE quality standard that this comparative example explanation parenteral solution quality standard content of the present invention and common process are produced has relatively increased new project, more meets intravenous requirement, has improved quality standard.

Project	ZHONGJIEFENG ZHUSHEYE quality standard of the present invention	Common process ZHONGJIEFENG ZHUSHEYE quality standard
			Check	PH value: should be 5.0～6.0.	PH value: should be 5.0～6.0.
	Protein: get this product 1ml, add 30% sulfosalicylic acid test solution 1ml of new preparation, mix, placed 5 minutes, muddiness must not occur.
				Oxalates: get this product 2ml, add 2～3 of 3% calcium chloride solutions, placed 10 minutes, muddiness or precipitation must not occur.
	Tannin: get this product 1ml, add the physiological saline 5ml that contains 1% egg of new preparation, placed 10 minutes, muddiness or precipitation must not occur.
				Potassium ion: get this product 2ml, evaporate to dryness burns to charing with little heated first, 500～600 ℃ of blazing extremely fully ashing, adds spirit of vinegar and makes dissolving again. Put in the 25ml measuring bottle, thin up is to scale, and mixing is as need testing solution. Get

	Two of 10ml nessler colorimetric tubes, accurate adding standard potassium ion solution 0.8ml in the first pipe, add alkaline formaldehyde solution and (get formalin, with 0.1mol/L sodium hydroxide solution adjust pH to 8.0～9.0) 12 droplets, 2 of 3% EDTA sodium solutions, 3% sodium tetraphenylborate solution 0.5ml, thin up becomes 10ml, the accurate need testing solution 1ml that adds in the second pipe with the simultaneously in accordance with the law operation of first pipe, shakes up, first, second two pipes are with putting on the black paper, from up to down have an X-rayed, the turbidity that shows in the second pipe and first pipe relatively must not be denseer.
				Resin: get this product 5ml, add 1 of hydrochloric acid, placed 30 minutes, should separate out without floccule.
	Pyrogen: get this product, check (an appendix XIII of Chinese Pharmacopoeia version in 2000 A) in accordance with the law, dosage is slowly injected 1ml by the every 1Kg of rabbit body weight, should be up to specification.
				Undue toxicity: get this product, check in accordance with the law and (two appendix XI of Chinese Pharmacopoeia version in 2000 C) press intravenous administration, should be up to specification.

Comparative example 2

Result's comparison that the ZHONGJIEFENG ZHUSHEYE of this comparative example explanation explained hereafter of the present invention and the ZHONGJIEFENG ZHUSHEYE of common process production detect with the quality standard of intravenously administrable, the ZHONGJIEFENG ZHUSHEYE of common process production can not be used for intravenous injection.

Project	The requirement of ZHONGJIEFENG ZHUSHEYE (intravenous injection) quality standard	The ZHONGJIEFENG ZHUSHEYE of explained hereafter of the present invention	The ZHONGJIEFENG ZHUSHEYE that common process is produced
				The pH value	Get this product, check that according to an appendix VII of Chinese Pharmacopoeia version in 2000 G the pH value is 5.0-6.0, and is up to specification.	(5.6 up to specification)	(5.6 up to specification)
Protein	Get this product 1ml, add 30% sulfosalicylic acid test solution 1ml of new preparation, mix, placed 5 minutes, muddiness must not occur. An appendix IX of Chinese Pharmacopoeia version in 2000 S " injection related substance inspection technique "	Up to specification	Up to specification
				Oxalates	Get this product 2ml, add 2～3 of 3% calcium chloride test solutions, placed 10 minutes, muddiness or precipitation must not occur. An appendix IX of Chinese Pharmacopoeia version in 2000 S " injection related substance inspection technique "	Up to specification	Against regulation
Tannin	Get this product 1ml, add the physiological saline 5ml that contains 1% egg of new preparation, placed 10 minutes, muddiness or precipitation must not occur. An appendix IX of Chinese Pharmacopoeia version in 2000 S " injection related substance inspection technique "	Up to specification	Against regulation
				Potassium ion	Get this product 1ml, evaporate to dryness burns to charing with little heated first, 500～600 ℃ of blazing extremely fully ashing, adds spirit of vinegar and makes dissolving again. Put in the 25ml measuring bottle, thin up is to scale, and mixing is as need testing solution. Get two of 10ml nessler colorimetric tubes, accurate adding standard potassium ion solution 0.8ml in the first pipe adds alkaline formaldehyde solution and (gets formalin, with 0.1mol/L sodium hydroxide solution adjust pH extremely	Up to specification	Against regulation

	8.0～9.0) 12,2 of 3% EDTA sodium solutions, 3% sodium tetraphenylborate solution 0.5ml, thin up becomes 10ml, the accurate need testing solution 1ml that adds in the second pipe, with the simultaneously in accordance with the law operation of first pipe, shake up, first, second two pipes are from up to down had an X-rayed with putting on the black paper, the turbidity that shows in the second pipe and first pipe relatively must not be denseer. The preparation of standard potassium ion solution: it is an amount of to get potassium sulfate, and porphyrize is dried to constant weight in 110 ℃, and precision takes by weighing 2.330g, puts in the 1000ml measuring bottle, adds water and makes in right amount dissolving and be diluted to scale, shakes up, as stock solution. Before use, precision is measured stock solution 10ml, puts in the 100ml measuring bottle, and thin up shakes up to scale, namely gets an appendix IX of (K that every ml is equivalent to 100 μ g) Chinese Pharmacopoeia version in 2000 S " injection related substance inspection technique "
				Resin	Get this product 5ml, add 1 of hydrochloric acid, placed 30 minutes, should separate out without floccule. An appendix IX of Chinese Pharmacopoeia version in 2000 S " injection related substance inspection technique "	Up to specification	Against regulation
Pyrogen	Foundation: Chinese Pharmacopoeia version in 2000 appendix XIII A " pyrogen test "	Up to specification	Against regulation
				Undue toxicity	Foundation: Chinese Pharmacopoeia version in 2000 two appendix XI C " abnormal toxicity tests method "	Up to specification	Up to specification

Comparative example 3

The explanation of this comparative example is processed the ZHONGJIEFENG ZHUSHEYE clarity of producing with process using clarification technique of the present invention, depositing in water refrigeration, charcoal treatment, centrifugation technique and is better than using the normal compound method to be produced.

	Adopt technique of the present invention	Adopt common process
			Method for making	Get Glabrous Sarcandra Herb 1000g, the water for injection boiling that adds 6 times of weight of Glabrous Sarcandra Herb decocts 2 times, and each 2 hours, Filter paper filtering merged filtrate twice, and concentrated every ml liquid contains crude drug amount 1g; Add 0.05% fining agent B of concentrate weight in the concentrate, be heated to 70～90 ℃, leave standstill 2 hours after, 0.025% the fining agent A that adds again concentrate weight, leave standstill 4 hours after, centrifugal, supernatant inclines and, and is concentrated into every ml liquid and contains crude drug amount 3g; Slowly stir the lower ethanol that adds, add ethanol and make that to contain the alcohol amount be 75%, 4-8 ℃ of refrigeration 48 hours, Filter paper filtering, filtrate recycling ethanol, and be concentrated into every ml liquid and contain crude drug amount 3g, add ethanol, make that to contain alcohol amount be 85 %, 4-8 ℃ refrigerates 48 hours, Filter paper filtering, filtrate recycling ethanol, concentrated filtrate, and be concentrated into every ml liquid and contain crude drug amount 6g; With the water for injection of 3 times of weight of concentrate, 4-8 ℃ refrigerates 24 hours, Filter paper filtering, filter	Get Glabrous Sarcandra Herb 1000g, boiling secondary, each 2 hours, collecting decoction filters, and it is 1.33 (70 ℃) that filtrate is concentrated into relative density, add ethanol precipitation secondary, make that to contain the alcohol amount be 70% for the first time, containing the alcohol amount for the second time is 80%, each refrigeration 48 hours filters, and filtrate recycling ethanol also is concentrated into every 1ml and contains crude drug 10g, the egg protein solution that adds the proper amount of fresh preparation stirs, precipitation, refrigerate 48 hours, filter, filtrate is boiled, excessive egg protein is solidified, filter, filtrate adds ethanol, make that to contain amount of alcohol be 75%, place precipitation, filter, filtrate recycling ethanol, it is an amount of to inject water, refrigerates 24 hours, filter, filtrate is with caustic lye of soda adjust pH to 9.0, and adding that active carbon makes is 0.05% concentration, boiled 30 minutes, and filtered, filtrate injecting is diluted with water to 1000ml, filter, add the 6ml polyoxyethylene sorbitan monoleate, stir evenly, filter, embedding, sterilization, and get final product.

	Liquid is regulated PH to 5.5 with 10% sodium hydroxide solution, the active carbon of adding 1%, boiled Filter paper filtering, centrifugal, ultrafiltration 30 minutes, add water for injection, make every ml contain fumaric acid 30 μ g, filter, with the filtering with microporous membrane of 0.22 μ m, can is in ampoule, and 100 ℃ of sterilizations in 30 minutes make. The resulting product specification is that 2ml/ props up.
			Clarity	5 have small particles in 200.	17 have white point, white piece, 5 deposited phenomenon to occur in 200.

Comparative example 4

Excitant was little when the explanation of this comparative example was used clinically with ZHONGJIEFENG ZHUSHEYE of the present invention, and bad reaction is few.

Nomenclature of drug	ZHONGJIEFENG ZHUSHEYE of the present invention	The common process ZHONGJIEFENG ZHUSHEYE
			Usage and dosage	Anti-inflammation: intramuscular injection, a 2～4ml, 1～2 time on the one; Drip-feed: a 4～12ml 1～2 time on the one, joins in 5%～10% glucose injection or 0.9% sodium chloride injection and uses.	Anti-inflammation: intramuscular injection, a 2～4ml, 1～2 time on the one;
Clinical use	Treat 65 routine bacillary dysentery patients	Treat 72 routine bacillary dysentery patients
			Beneficial effect	97% patient cured in 2 days	91% patient cured in 3 days
Bad reaction is observed	Without phenomenons such as itch all over, uncomfortable in chest, weak, fash, palpitaition, allergy.	2 routine fash phenomenons are arranged
			Excitant is observed	5 examples have the pain phenomenon	7 examples have the pain phenomenon, and there is constriction 4 routine injection sites

Comparative example 5

This comparative example explanation ZHONGJIEFENG ZHUSHEYE of the present invention and common process ZHONGJIEFENG ZHUSHEYE compare by the stability of acceleration in 6 months

	ZHONGJIEFENG ZHUSHEYE of the present invention	The common process ZHONGJIEFENG ZHUSHEYE
			Standard code	The every 1ml of this product contains fumaric acid (C4H 4O 4) must not be less than 60 μ g (antitumor usefulness). Clarity: qualification rate is greater than 95% pH value: 5.0～6.0	The every 1ml of this product contains fumaric acid (C4H 4O 4) must not be less than 60 μ g (antitumor usefulness). Clarity: qualification rate is greater than 95% pH value: 5.0～6.0
0 month	Fumaric acid content: 78 μ g clarity: qualification rate 99% pH value: 5.6	Fumaric acid content: 75 μ g clarity: qualification rate 99% pH value: 5.6
			1 month	Fumaric acid content: 78 μ g clarity: qualification rate 99% pH value: 5.6	Fumaric acid content: 75 μ g clarity: qualification rate 98% pH value: 5.6

2 months	Fumaric acid content: 78 μ g clarity: qualification rate 99% pH value: 5.6	Fumaric acid content: 73 μ g clarity: qualification rate 97% pH value: 5.5
			3 months	Fumaric acid content: 77 μ g clarity: qualification rate 99% pH value: 5.6	Fumaric acid content: 71 μ g clarity: qualification rate 96% pH value: 5.3
6 months	Fumaric acid content: 77 μ g clarity: qualification rate 99% pH value: 5.6	Fumaric acid content: 65 μ g clarity: qualification rate 95% pH value: 5.1

Show that by above data the quality stability of ZHONGJIEFENG ZHUSHEYE of the present invention is better than the common process ZHONGJIEFENG ZHUSHEYE.

Claims (11)

1, a kind of ZHONGJIEFENG ZHUSHEYE, for the Glabrous Sarcandra Herb poach, concentrated, add fining agent clarification, alcohol precipitation and obtain Glabrous Sarcandra Herb active component preparation through post processing.

2, parenteral solution according to claim 1 is characterized in that described post processing comprises that the liquid that alcohol precipitation is also concentrated is dissolved in water, refrigerates rear filtration, regulates PH, ultrafiltration, packing and sterilization.

3, parenteral solution according to claim 1 and 2 is characterized in that every milliliter of described ZHONGJIEFENG ZHUSHEYE contains fumaric acid and is no less than 30 μ g.

4, a kind of preparation method of ZHONGJIEFENG ZHUSHEYE, it is characterized in that with the Glabrous Sarcandra Herb poach, concentrated, add fining agent clarification, alcohol precipitation and obtain through post processing.

5, method according to claim 4 is characterized in that described post processing comprises that the liquid that alcohol precipitation is also concentrated adds water, the rear filtration of refrigeration, adjusting PH, ultrafiltration, packing and sterilization.

6, preparation method according to claim 4 is characterized in that described preparation method is:

(1) poach, concentrated: get Glabrous Sarcandra Herb 1-1000 weight portion, the water boiling that adds 3-8 times of weight decocts 2 times, and each 2-3 hour, filter, merge twice filtrate, concentrated;

(2) add the fining agent clarification: 0.03%～0.06% the fining agent that adds concentrate weight in the concentrate, be heated to 70～90 ℃, leave standstill, add again 0.015%～0.03% fining agent of concentrate weight, leave standstill rear centrifugally, get supernatant concentration;

(3) alcohol precipitation: slowly stir lower adding ethanol and carry out alcohol precipitation, filter after the 4-8 ℃ of refrigeration, filtrate recycling ethanol, and be concentrated into every milliliter of liquid and contain crude drug amount 3～4g, add ethanol, make to contain the alcohol amount for 80-85 %, filter after the 4-8 ℃ of refrigeration, filtrate recycling ethanol, concentrated filtrate to every milliliter of liquid contains crude drug amount 6～8g;

(4) post processing: with the water for injection of concentrate 1-3 times weight, refrigerate after 24 hours and filter, filtrate is regulated PH to 5.0-6.0 with the 10-20% sodium hydroxide solution, the active carbon of adding 1%, boil, filtration, centrifugal, ultrafiltration, add water for injection, filtration, use filtering with microporous membrane again, can is sterilized in ampoule and is made.

7, according to claim 3 each described preparation method-5, it is characterized in that poach and filtrate after, filtrate is concentrated into every ml liquid and contains crude drug amount 1～2g.

8, according to claim 3 each described preparation method-5 is characterized in that adding and liquid is concentrated into every ml liquid before the ethanol and contains crude drug amount 3～4g.

9, according to claim 3 each described preparation method-5, it is characterized in that depositing in water before, filtrate is concentrated into every ml liquid and contains crude drug amount 6～8g.

10, according to claim 3 or 4 described preparation methods, it is characterized in that ultrafiltration after, add water for injection and contain fumaric acid 30～300 μ g to every ml; Centrifugal revolution is 4000 rev/mins; It is 100,000 ultrafiltration post that molecular cut off is selected in ultrafiltration.

11, each described intravenously administrable Glabrous Sarcandra Herb injection of claim 1-3.