CN1044760A

CN1044760A - Preparation of injection of Chinese medicines

Info

Publication number: CN1044760A
Application number: CN 89106021
Authority: CN
Inventors: 赵喜胜; 周伯旭; 隋明
Original assignee: HEILONGJIANG INSTITUTE OF TRADITIONAL CHINESE MEDICINE
Current assignee: HEILONGJIANG INSTITUTE OF TRADITIONAL CHINESE MEDICINE
Priority date: 1989-11-11
Filing date: 1989-11-11
Publication date: 1990-08-22
Anticipated expiration: 2004-11-11
Also published as: CN1023375C

Abstract

Preparation of injection of Chinese medicines is made SHUANGHUANGLIAN FENZHENJI, be to make through extracting refining by Flos Lonicerae, Radix Scutellariae, Fructus Forsythiae three flavor Chinese medicines, the present invention handles the effective ingredient baicalin that extracts in the refining Radix Scutellariae with acid-base method alcohol, Flos Lonicerae, Fructus Forsythiae are handled with water alcohol method, two parts are mixed and made into the SHUANGHUANGLIAN FENZHENJI semi-finished product, through being mixed with the aqueous solution of suitable concentration, use freeze-drying to remove wherein moisture more then, make the SHUANGHUANGLIAN FENZHENJI of porous solid shape.

Description

Preparation of injection of Chinese medicines

The present invention belongs to the method for preparing the Chinese medicine powder injection.

Present existing SHUANGHUANLIAN aqueous injection exists poor stability, is prone to phenomenons such as turbidity sediment in the long preservation process, and is not easy to storing; In the technology of preparation SHUANGHUANGLIAN ZHUSHEYE, three kinds of methods are arranged now: 1. Flos Lonicerae, Fructus Forsythiae, Radix Scutellariae all extract separately; 2. this three flavors Chinese medicine mixes with water alcohol method and handles; 3. this three flavors Chinese medicine mixes with the method for alcohol dipping and handles; Preceding a kind of method complex operation, difficult quality control, back two kinds of method active ingredients loss is bigger, and clinical effectiveness is difficult to guarantee.

The objective of the invention is to propose a kind of method for preparing SHUANGHUANGLIAN FENZHENJI, and solve the technical barrier of preparation SHUANGHUANGLIAN ZHUSHEYE technology existence at present.

SHUANGHUANGLIAN FENZHENJI is Flos Lonicerae, Radix Scutellariae, Fructus Forsythiae three flavor Chinese medicines compositions, the present invention extracts refining baicalin with acid-base method, Flos Lonicerae, Fructus Forsythiae are handled with water alcohol method, it is 1: 7 aqueous solution that last two parts are mixed and made into concentration, use freeze-drying to remove wherein moisture content again, make the SHUANGHUANGLIAN FENZHENJI of porous solid shape.Main processes has following four steps: one, the extraction of baicalin; Two, the extraction of Flos Lonicerae, Fructus Forsythiae; Three, the half-finished preparation of SHUANGHUANGLIAN FENZHENJI; Four, SHUANGHUANGLIAN FENZHENJI finished product preparation; Its specific embodiment is as follows:

One, the extraction of baicalin: be to adopt acid-base method to extract to make with extra care, the Radix Scutellariae section, adding 8 times of water gagings boiled 1 hour, filter, 3 times of water gagings of medicinal residues reuse boiled 1 hour, filter, twice filtrate merges with concentrated hydrochloric acid transfers PH to 1-2, is heated to 80 ℃ and is incubated half an hour, and the baicalin crude product is separated out, the leaching precipitation, add the water of precipitate 8 deals, stir evenly, the baicalin crude product is suspended in the water, transfer PH7.0 with 40% sodium hydroxide solution, 95% ethanol that adds equivalent again stirs, and adds concentrated hydrochloric acid and transfers PH2 and be heated to 50 ℃, be incubated half an hour, baicalin is separated out, filter, precipitate with 95% washing with alcohol, dry baicalin, the baicalin pulverizing is added 10 times of water gagings make its suspendible, transfer PH to 6.0, add active carbon in baicalin crude product weight 3% with 40% sodium hydroxide solution, stir 50 ℃ and be incubated half an hour, add and filter immediately after equivalent 95% ethanol stirs evenly, filtrate is transferred PH to 3.0 with concentrated hydrochloric acid, and 60 ℃ are incubated half an hour, baicalin is separated out, centrifugal filtration, with a small amount of 95% washing with alcohol precipitation, centrifugal filtration is to doing, below 60 ℃ the oven dry, pulverize refining baicalin.

Two, Flos Lonicerae, the extraction of Fructus Forsythiae: refining with the water alcohol method extraction, Flos Lonicerae, the Fructus Forsythiae decoction pieces is soaked half an hour, decoct 2 times, each 1.5 hours, filter, merging filtrate is concentrated into proportion 1.1～1.12(70-80 ℃), the 85-90% ethanol that slowly adds 3 times of amounts fully stirs under 35-40 ℃ temperature, after the cooling, placed centrifugal filtration, residue 55-60% washing with alcohol secondary 12 hours, merge, filtrate recycling ethanol is to there not being the alcohol flavor, add the ethanol of 5 times of amounts more than 90% again, under 35-40 ℃ temperature, fully stir, after the cooling, placed 12 hours, the leaching supernatant, filtrate recycling ethanol adds the distilled water of 3 times of amounts to there not being the alcohol flavor, transfers PH to 7.0 fully to stir, be heated to boiling, placed 24 hours, the leaching supernatant is concentrated into proportion 1.1-1.15(70-80 ℃) add the ethanol of 8 times of amounts of this volume, under 35-40 ℃ temperature, fully stir, after the cooling, placed 48 hours, the leaching supernatant reclaims ethanol to there not being the alcohol flavor.Make double flower forsythia extract.

Three, the half-finished preparation of SHUANGHUANGLIAN FENZHENJI: reclaiming alcoholic acid Flos Lonicerae, adding refining baicalin in the Fructus Forsythiae extract, heating, and add 40% sodium hydroxide solution and transfer PH to 7.0, and remaining on baicalin is dissolved fully, it is to add 0.5% active carbon at 1: 7 that adding distil water is transferred concentration, 100 ℃ are incubated 15 minutes, after the cooling, filter the filtrate embedding, 115 ℃ of pressure sterilizings, 30 minutes, cold preservation got the SHUANGHUANGLIAN FENZHENJI semi-finished product.

Four, the preparation of SHUANGHUANGLIAN FENZHENJI: under aseptic condition, the SHUANGHUANGLIAN FENZHENJI semi-finished product are filtered, adding sterile purified water accent concentration is 1: 5, transfer PH to 6.5 with 40% sodium hydroxide solution, add sterile purified water, transferring concentration is 1: 4, fine straining, filtrate is sub-packed in the 10ml bottle, every 2.5 or 5ml and be placed in the freeze dryer after freezing 4 hours, make the plate temperature reach-17.5 ℃, products temperature reaches-23 ℃, chilling temperature reaches-40 ℃, evacuation, and the plate temperature slowly is increased to 20 ℃ subsequently, products temperature also increases to 20 ℃, condensation temperature is constant, unpacks after 24 hours, makes lyophil apparatus, gland, labeling gets SHUANGHUANGLIAN FENZHENJI.

The present invention is complete to three flavor Chinese medicine extracts active ingredients in the prescription than other SHUANGHUANGLIAN ZHUSHEYE extraction processes, lose lessly, easy and simple to handle, and quality is easy to control, and clinical efficacy is remarkable; Can reduce heating process to greatest extent with lyophilization, than other technologies effective ingredient is destroyed minimizing, effect duration is longer, process of assembling all carried out under aseptic purification condition in whole minute, so pyrogen, aseptic, microgranule is easy to control, and the present invention obtains SHUANGHUANGLIAN FENZHENJI, and every technical specification all meets the version Pharmacopoeia of the People's Republic of China in 1985 requirement.

The embodiment of the invention:

SHUANGHUANGLIAN FENZHENJI is to be made through extracting refining by Flos Lonicerae, Radix Scutellariae, Fructus Forsythiae three flavor Chinese medicines.Prescription: Flos Lonicerae 2500g, Radix Scutellariae 2500g, Fructus Forsythiae 5000g makes 500 SHUANGHUANGLIAN FENZHENJI.One, the extraction of baicalin: the utilization acid-base method extracts refining baicalin, Radix Scutellariae is cut into slices, added 80,000 ml water boils 1 hour, filter, medicinal residues reuse 30,000 ml water boils 1 hour filter, and twice filtrate merges, transfer PH1-2 with concentrated hydrochloric acid, be heated to 80 ℃ and be incubated half an hour, the baicalin crude product is separated out, the leaching precipitation, the distilled water that adds 8 times of amounts, stir, the baicalin crude product is suspended in the water, transfer PH7.0 with 40% sodium hydroxide solution, 95% ethanol that adds equivalent again, stir, add concentrated hydrochloric acid and transfer PH2, and be heated to 50 ℃, be incubated half an hour, baicalin is separated out, filter, precipitate with 95% washing with alcohol, dry baicalin, baicalin is pulverized the distilled water that adds 10 times of amounts make its suspendible, transfer PH to 6.0, add active carbon by baicalin crude product weight 3% with 40% sodium hydroxide solution, stir, be heated to 50 ℃ and be incubated half an hour, add equivalent 95% ethanol, filter immediately after the stirring, filtrate is transferred PH to 3.0 with concentrated hydrochloric acid, 60 ℃ are incubated half an hour, baicalin are separated out, centrifugal filtration, below 60 ℃ the oven dry, pulverize refining baicalin.Two, Flos Lonicerae, the extraction of Fructus Forsythiae is refining: Flos Lonicerae, the Fructus Forsythiae decoction pieces, soak half an hour, decoct twice, each 1.5 hours, filter, merging filtrate, dope is to 1.1-1.12(70-80 ℃) slowly add the 85-90% ethanol of about 3 times of amounts, under 35-40 ℃ temperature, fully stir, after the cooling, placed 12 hours, centrifugal leaching supernatant, residue 55-60% washing with alcohol secondary filter, filtrate recycling ethanol, to there not being the alcohol flavor, add the ethanol of about 5 times of amounts more than 90% again, fully stir under 35-40 ℃ temperature, placed 12 hours the cooling back, the leaching supernatant, filtrate recycling ethanol adds the ethanol of 5 times of amounts more than 90% again to there not being the alcohol flavor, fully stirs under 35-40 ℃ temperature, placed 12 hours the cooling back, the leaching supernatant, filtrate recycling ethanol adds 3 times of amount distilled water to there not being the alcohol flavor, transfer PH to 7.0 fully to stir, be heated to boiling, placed the leaching supernatant 24 hours, be concentrated into proportion 1.1-1.15(70-80 ℃) add the ethanol of 8 times of amounts of this volume, fully stir under 35-40 ℃ temperature, the cooling back was placed the leaching supernatant 48 hours, reclaim ethanol to there not being the alcohol flavor, make Flos Lonicerae, Fructus Forsythiae extract.Three, SHUANGHUANGLIAN FENZHENJI semi-finished product preparation: add purified baicalin at Flos Lonicerae, Fructus Forsythiae extract, heating, and add 40% sodium hydroxide solution and transfer PH to 7.0, and remain on baicalin is dissolved fully, adding distil water is to 1500ml, add 0.5% active carbon, be heated to and boil and kept 15 minutes, after the cooling, filter with filter press, filtrate is irritated in the 500ml infusion bottle, 115 ℃ of gland pressure sterilizings, 30 minutes; A week is hidden in refrigerator and cooled in the cooling back.Four, the preparation of SHUANGHUANGLIAN FENZHENJI: under aseptic condition, with SHUANGHUANLIAN semi-finished product G ₁The sintered glass funnel decompress filter adds sterile purified water 2000ml, transfers PH6.5 with 40% sodium hydroxide solution, adds sterile purified water to 2500ml, and concentration is 1: 4, with filter press pressurization passing through G ₃Sintered glass filter-bulb, microporous filter membrane (0.65u), filtrate is sub-packed in the 10ml bottle, every 2.5ml and be placed on freeze dryer cooled off after 4 hours, made the plate temperature reach-17.5 ℃, products temperature reaches-23 ℃, and condensation temperature reaches-40 ℃, evacuation, the plate temperature slowly is increased to 20 ℃ subsequently, and products temperature increases to 20 ℃, and chilling temperature is constant, unpack after 24 hours, make dried frozen aquatic products, gland, labeling get SHUANGHUANGLIAN FENZHENJI.

Claims

1, a kind of preparation of injection of Chinese medicines is characterized in that extracting refining baicalin with acid-base method, extracts refining Flos Lonicerae with water alcohol method, Fructus Forsythiae, to make with extra care baicalin then mixes with double flower forsythia extract, make concentration and be 1: 7 SHUANGHUANGLIAN FENZHENJI semi-finished product, the SHUANGHUANGLIAN FENZHENJI semi-finished product are filtered transfer pH value, adjust finite concentration, use freeze-drying at last, be made into SHUANGHUANGLIAN FENZHENJI, its main process is as follows: Radix Scutellariae water extraction 2 times, filter, merging filtrate, with its furnishing acidity, heat tracing, leaching precipitation, transfer pH value to neutral, add equivalent 95% ethanol, filter, filtrate transfers pH value to acid, heat tracing, the leaching precipitation is transferred the pH value faintly acid, adds 3% active carbon heating, temperature keeping after 30 minutes, filter immediately, the filtrate acid adjustment, heat tracing, the leaching precipitation, 95% washing with alcohol, centrifugal filtration, must make with extra care baicalin, Flos Lonicerae, Fructus Forsythiae water extraction 2 times are filtered, concentrate, successively secondary Different concentrations of alcohol precipitate with ethanol filters filtrate recycling ethanol, water precipitating once, the reuse high concentration ethanol, precipitate with ethanol filters, filtrate recycling ethanol, get double flower forsythia extract, refining baicalin mixes with double flower forsythia extract, adds active carbon, transferring concentration is 1: 7, filter, sterilize the SHUANGHUANGLIAN FENZHENJI semi-finished product, the SHUANGHUANGLIAN FENZHENJI semi-finished product are filtered, be mixed with the aqueous solution of 1: 5 concentration, transfer pH value to 6.5, adding sterile purified water accent concentration is 1: 4, and fill is in bottle, lyophilization gets SHUANGHUANGLIAN FENZHENJI.

2, according to the described preparation of injection of Chinese medicines of claim 1, it is characterized in that Radix Scutellariae filters through water extraction 2 times after, transfer PH1-2 with concentrated hydrochloric acid, be heated to 80 ℃ of insulations 30 minutes, the leaching precipitation gets the baicalin crude product, add 8 times of amount distilled water, the baicalin crude product is suspended in the water, transfer PH7.0 with 40% sodium hydroxide solution, add equivalent 95% ethanol again, add concentrated hydrochloric acid and transfer PH2, be heated to 50 ℃ of insulations 30 minutes, the leaching precipitation, with 95% washing with alcohol, get baicalin.

3, according to claim 1,2 described preparation of injection of Chinese medicines, it is characterized in that the baicalin pulverizing is added 10 times of amount distilled water makes its suspendible, transfer PH6, add active carbon by baicalin weight 3% with 40% sodium hydroxide solution, 50 ℃ of agitating heating, be incubated half an hour, add equivalent 95% ethanol, filter immediately after the stirring, filtrate is transferred PH to 3.0 with concentrated hydrochloric acid, heat 60 ℃ and be incubated half an hour, the leaching precipitation must be made with extra care baicalin with 95% washing with alcohol.

4, according to the described preparation of injection of Chinese medicines of claim 1, it is characterized in that Flos Lonicerae and Fructus Forsythiae is through water extraction 2 times, filter, filtrate is concentrated into proportion 1.10-1.12(70-80 ℃), add 3 times of amount 85-90% ethanol, under 35-40 ℃ temperature, stir, after the cooling, placed 12 hours, filter, residue 55-60% washing with alcohol secondary, filtered and recycled ethanol adds the ethanol of 5 times of amounts more than 90% again, under 35-40 ℃ temperature, fully stir, the cooling back was placed leaching supernatant, filtrate recycling ethanol 12 hours.

5,, it is characterized in that the intact alcoholic acid Flos Lonicerae of recovery, Fructus Forsythiae extracting solution as preparation of injection of Chinese medicines as described in the claim 1,4, the distilled water that adds 3 times of amounts is transferred PH7, is heated to 100 ℃, placed 24 hours, and filtered, filtrate is to 1.10-1.15(70-80 ℃).

6, according to claim 1,5 described preparation of injection of Chinese medicines, it is characterized in that concentrate Flos Lonicerae and Fructus Forsythiae liquid in, adds 8 times and measures 95% ethanol, under 35-40 ℃ temperature, fully to stir, placed 48 hours the cooling back, the leaching supernatant reclaims ethanol, gets double flower forsythia extract.

7, preparation of injection of Chinese medicines according to claim 1 is characterized in that baicalin is added in the double flower forsythia extract, and PH7 is transferred in heating, and remain on PH7, make the baicalin dissolving fully, adding distil water is as 0.5% active carbon, heat 100 ℃ 15 minutes, filter, transferring concentration is 1: 7, and the filtrate embedding is in the 500ml bottle, 115 ℃ of pressure sterilizings 30 minutes are made the SHUANGHUANGLIAN FENZHENJI semi-finished product.

8, according to claim 1,7 described preparation of injection of Chinese medicines, it is characterized in that under the aseptic condition, the SHUANGHUANGLIAN FENZHENJI semi-finished product are filtered, add sterile purified water and make concentration to 1: about 5, transfer PH6.5, add sterile purified water and transferred concentration 1: 4, filter, be sub-packed in the 10ml bottle.

9, according to right 1,8 described preparation of injection of Chinese medicines, it is characterized in that preparing SHUANGHUANGLIAN FENZHENJI the bottle that branch is installed with freeze-drying, place freeze dryer, freezing 4 hours, make the plate temperature reach-17.5 ℃, products temperature reaches-23 ℃, condensation temperature-40 ℃, evacuation, the plate temperature slowly is increased to 20 ℃ subsequently, products temperature also increases to 20 ℃, condensation temperature is constant, unpacks after 24 hours, makes SHUANGHUANGLIAN FENZHENJI.