CN103239395A - Houttuynia cordata injection and preparation method thereof - Google Patents
Houttuynia cordata injection and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a houttuynia cordata injection and a preparation method thereof. According to the houttuynia cordata injection prepared by using the preparation method of the invention, the existing production process is adopted on the basis of a legal department standard, each production link and parameters are defined and detailed, and dosage of polysorbate 80 is reduced. The houttuynia cordata injection prepared by using the preparation method disclosed by the invention is stable and uniform in different batches, and a cell membrane breaking effect caused by the polysorbate 80 is reduced, irritation, hemolysis and histamine release are reduced, and medication safety is improved.
Description
Patent application of the present invention is for dividing an application, and the original bill application number is 201110205127.3, and the applying date is on July 21st, 2011, and denomination of invention is a kind of preparation method of Herba Houttuyniae injectio.
Technical field:
The present invention relates to a kind of preparation method of injection, particularly relate to a kind of method of utilizing the Herba Houttuyniae herb to be prepared Herba Houttuyniae injectio.
Background technology
Herba Houttuyniae is the whole herb with root of Saururaceae herbaceos perennial Herba Houttuyniae Houttuynia cordata Thunb., have another name called Herba Houttuyniae, purple Ji, hog snout hole, Rhizoma Rohdeae Japonicae etc., after its fresh plant fragmentation pungent stench flavor is arranged, be distributed widely in China middle part, the southeast and each provinces and regions, southwest, economize in the majority with Hunan, Hubei, Sichuan, Jiangsu etc. especially.Herba Houttuyniae has the effect of heat-clearing and toxic substances removing, eliminating carbuncle evacuation of pus, inducing diuresis for treating stranguria syndrome, clinical for lung abscess vomiting pus, expectorant dyspnea of heat type cough, disease such as hematodiarrhoea, pyretic stranguria, carbuncle sore tumefacting virus.Studies show that, contain compositions such as volatile ingredient, flavonoid, organic acid, sterols, alkaloids in the Herba Houttuyniae.Herba Houttuyniae injectio is to get through the steam distillation preparation, and main component is its volatile ingredient.
At ministry standard WS
3The addition of [method for making] of Herba Houttuyniae injectio regulation polyoxyethylene sorbitan monoleate is 0.5% among the-B-3264-98, but safety research shows that polyoxyethylene sorbitan monoleate has the effect of very strong ruptured cell film and causes zest, hemolytic and histamine release (sensitization).Medical circle confirms that polyoxyethylene sorbitan monoleate is used for injection, can cause allergic reaction, and comprises anaphylactoid reaction symptoms such as shock, dyspnea, hypotension, angioedema, rubella.
Summary of the invention
The object of the invention is to disclose a kind of preparation method of Herba Houttuyniae injectio.
The present invention seeks to be achieved by the following scheme:
The preparation method of Herba Houttuyniae injectio of the present invention comprises the steps:
(1) be that 1:1-3.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carry out vapor distillation, collect distillate 1000-3000 parts by volume just, carry out redistillation again, collect re-distilled liquid 700-1300 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰-3 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
The preparation method of Herba Houttuyniae injectio of the present invention preferably includes following steps:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) by weight/volume is 2.5 ‰ polyoxyethylene sorbitan monoleate in the re-distilled liquid, stirs and makes dissolving in 10 minutes, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and it is 5.0-6.0 that the citric acid soln with 10% is regulated pH value;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
The preparation method of Herba Houttuyniae injectio of the present invention also preferably includes following steps:
(1) is that 1:3 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 1500 parts by volume just, carry out redistillation again, collect re-distilled liquid 850 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.9 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 8 minutes, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
The preparation method of Herba Houttuyniae injectio of the present invention also preferably includes following steps:
(1) is that 1:1.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2500 parts by volume just, carry out redistillation again, collect re-distilled liquid 1300 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.6 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 15 minutes, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
The preparation method of Herba Houttuyniae injectio of the present invention preferably includes following steps:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.7 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
The preparation method of Herba Houttuyniae injectio of the present invention preferably includes following steps:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.9 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
The preparation method of Herba Houttuyniae injectio of the present invention preferably includes following steps:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 3 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
The preparation method of Herba Houttuyniae injectio of the present invention preferably includes following steps:
(1) is that 1:1.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
The preparation method of Herba Houttuyniae injectio of the present invention preferably includes following steps:
(1) is that 1:2.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
Wherein, between above-mentioned weight portion and the parts by volume be the relation of g/ml.
The present invention in existing production technology on legal ministry standard basis, clear and definite and refinement each production link and parameter, on the basis of safety research, reduced the polyoxyethylene sorbitan monoleate consumption, technological procedure and the quality standard formulated, the stable uniform of control production overall process and assurance different batches product.Reduce effect and the zest that causes, hemolytic and the histamine release (sensitization) of the ruptured cell film that polyoxyethylene sorbitan monoleate causes, improved drug safety.
The present invention has carried out refinement and perfect to the Herba Houttuyniae injectio preparation process, and result of study shows: the polyoxyethylene sorbitan monoleate consumption is 0.25%; The pH value regulator changes to 10% citric acid soln; By to Herba Houttuyniae re-distilled liquid, adjuvant, intermediate and production process and the control of pyrogen bacterial endotoxin is controlled in the control of microorganism and pyrogen is controlled in the control of microorganism; Sterilizing parameter is 115 ℃ of 32 minutes (F
08).
By 10 batches of Herba Houttuyniae injectio of trial production in the existing production technology of determining, constant product quality meets the internal control quality standard of formulation.Illustrate that existing production technology is stable and controllable, guaranteed different batches constant product quality homogeneous.
Description of drawings
Accompanying drawing 1 Guangzhou chemistry polyoxyethylene sorbitan monoleate cmc figure
Accompanying drawing 2 Nanjing Weir polyoxyethylene sorbitan monoleate cmc figure
Accompanying drawing 3 Britain croda polyoxyethylene sorbitan monoleate cmc figure
Accompanying drawing 4 Japan day oily polyoxyethylene sorbitan monoleate cmc figure
The polyoxyethylene sorbitan monoleate of accompanying drawing 5 different amounts is to the figure that influences of Herba Houttuyniae re-distilled liquid content
Following experimental example and embodiment further specify but are not limited to the present invention.
The screening of experimental example 1 Herba Houttuyniae medicinal part ratio
The raw material of Herba Houttuyniae injectio of the present invention is bright Herba Houttuyniae, and medicinal part divides aerial parts and under ground portion.To zones of different, Various Seasonal, different year, differently the content of top and under ground portion and weight are measured, and have determined the ingredient proportion of aerial parts under ground portion, and the result is as follows:
(1) Herba Houttuyniae aerial parts and the under ground portion of zones of different, different year are measured content respectively, the results are shown in Table 1.
Table 1 zones of different Herba Houttuyniae aerial parts and under ground portion content results
Annotate: isopropyl alcohol component A:4-methyl isophthalic acid-isopropyl-3-cyclohexene-1-alkoxide component B:2-(4-methyl-3-cyclohexenyl group)
Component C: borneol acetate component D: methylnonanone
Above result shows: Herba Houttuyniae under ground portion four constituent contents of zones of different are the content on top above Ground all; Biennial under ground portion four constituent contents are higher than annual under ground portion content; Annual aerial parts four constituent contents will be higher than biennial aerial parts; Four constituent contents with regional aerial parts differ greatly, but the content difference of under ground portion is less, and are relatively stable.
(2) Various Seasonal Herba Houttuyniae aerial parts and under ground portion are measured content respectively, the results are shown in Table 2.
The content results of table 2 Various Seasonal Herba Houttuyniae ground, under ground portion
Above result shows: Herba Houttuyniae under ground portion four constituent contents of Various Seasonal are the content on top above Ground all.The content difference of Various Seasonal aerial parts is bigger, but the content difference of under ground portion is less, and is relatively stable.
(3) different times Herba Houttuyniae aerial parts and under ground portion weight:
Get Herba Houttuyniae 5 strains, weigh respectively aerial parts and under ground portion are averaged, and the calculated weight ratio the results are shown in Table 3.
Table 3 Various Seasonal Herba Houttuyniae aerial parts and under ground portion weight result
Above result shows: the Herba Houttuyniae aerial parts weight of Various Seasonal all is less than under ground portion weight, and aerial parts and under ground portion weight ratio are between 1:1 to 1:3.
Above-mentioned studies show that, because Herba Houttuyniae under ground portion content is than aerial parts content height, Heavy Weight, and the content of Various Seasonal, zones of different is than stable uniform, is to guarantee different batches constant product quality homogeneous, so the ingredient proportion of top and under ground portion is 1:2 definitely.
The screening of experimental example 2 Herba Houttuyniae extraction processes
1, raw medicinal material of the present invention just distills the investigation of quantity of distillate
Get the embodiment of the invention 1 described raw medicinal material 1kg, selection is cleaned, and cuts off, and drops in the round-bottomed flask, adds purified water 1.8 ten thousand ml.Open cold condenser water intaking valve is opened the electric jacket heating, collects distillate just.Control distillate temperature is less than 40 ℃.Collect 0-1000ml, 1000-1100ml, 2000-2100ml, 3000-3100ml, 4000-4100ml, 5000-5100ml, the first distillate sample of 6000-6100ml, 7000-7100ml, 8000-8100ml, 9000-9100ml, 10000-10100ml, 11000-11100ml, 12000-12100ml, 13000-13100ml, numbering 0-12.The content of working sample.Raw medicinal material of the present invention just distills quantity of distillate and the results are shown in Table 4.
Table 4 raw medicinal material just distills the quantity of distillate experimental result
Annotate: isopropyl alcohol component A:4-methyl isophthalic acid-isopropyl-3-cyclohexene-1-alkoxide component B:2-(4-methyl-3-cyclohexenyl group)
Component C: borneol acetate component D: methylnonanone
Last table shows: when distilling the distillate volume originally and be ten times of inventory weight (10000ml), component A, B, C, D distillate substantially fully.When distillate volume when being one times of Herba Houttuyniae inventory weight (1000ml), component A, B, C, D have distillated major part, and component D also has part not distillate, and may be because component D content is higher, due to the reason of poorly water-soluble.
2, the investigation of raw medicinal material redistillation quantity of distillate of the present invention
Get the embodiment of the invention 1 described raw medicinal material 1kg, selection is cleaned, and cuts off, and drops in the round-bottomed flask, adds the about 2000ml of purified water.Open cold condenser water intaking valve is opened the electric jacket heating, collects distillate 1000ml just.First distillate is put into round-bottomed flask, put into zeolite, open cold condenser water intaking valve is opened the electric jacket heating, collects double distilled liquid.Control distillate temperature is less than 30 ℃.Collect 100-200ml, the re-distilled liquid sample of 500-600ml, 700-800ml is numbered a, b, c.The content of working sample.Raw medicinal material redistillation quantity of distillate of the present invention the results are shown in Table 5.
Table 5 raw medicinal material redistillation of the present invention quantity of distillate experimental result
Annotate: isopropyl alcohol component A:4-methyl isophthalic acid-isopropyl-3-cyclohexene-1-alkoxide component B:2-(4-methyl-3-cyclohexenyl group)
Component C: borneol acetate component D: methylnonanone
Last table shows: when redistillation distillate volume was 1/2 times of Herba Houttuyniae inventory, the component A in the first distillate, B, C, D all distillated fully.
The investigation of the rate of transform of experimental example 3 Herba Houttuyniae medical material-re-distilled liquids
Obtain the Herba Houttuyniae re-distilled liquid according to the prepared described in the embodiment of the invention 1.Be 50-80 ten thousand ml in batches, totally 5 batches, the rate of transform of calculating Herba Houttuyniae medical material-re-distilled liquid the results are shown in Table 6.
The rate of transform of table 6 Herba Houttuyniae medical material-re-distilled liquid
Annotate: isopropyl alcohol component A:4-methyl isophthalic acid-isopropyl-3-cyclohexene-1-alkoxide component B:2-(4-methyl-3-cyclohexenyl group)
Component C: borneol acetate component D: methylnonanone
Table 6 is the result show:
(1) Herba Houttuyniae medical material-re-distilled liquid mean transferred rate is component A58.1%, B component 56.2%, component C5.1%, component D4.2%, the rate of transform of component A, B is than higher, the rate of transform of component C, D is lower, because what this product was collected is the saturated Aromatic water of Herba Houttuyniae, may be that the rate of transform that causes of component C, D poorly water-soluble is lower.
Four components contents of (2) five batches of Herba Houttuyniae differ greatly, particularly the content of component C, D differs bigger, but the Herba Houttuyniae re-distilled liquid that obtains according to existing Herba Houttuyniae redistillation production technology, content difference between batch is little, than homogeneous, stability better proves that existing redistillation production technology can overcome the difference of Herba Houttuyniae medical material itself, can guarantee the stable uniform of different batches product quality.
The screening of embodiment 4 solubilizing agent polyoxyethylene sorbitan monoleates
Herba Houttuyniae injectio is to be made through the volatile oil saturated aqueous solution of vapor distillation by bright Herba Houttuyniae, and used re-distilled liquid is made up of water-soluble fragrance ingredient, two kinds of forms of water-fast suspendible emulsion.This unstabilizing liquid, heterogeneity can not be directly used in injection, and preparation need be selected solubilizing agent for use.
Polyoxyethylene sorbitan monoleate (Tween80) belongs to the hydrophilic non-ionic surface active agent, soluble in water, methanol, ethanol and ethyl acetate.Owing to have long carbon-chain structure in its structure, lipophilic drugs there is hydrotropy effect preferably, when preparation insoluble drug preparation, be commonly used for cosolvent, emulsifying agent and stabilizing agent etc., particularly in Chinese medicine, use extensively.Therefore, select for use polyoxyethylene sorbitan monoleate as the solubilizing agent of this preparation.
(1) polyoxyethylene sorbitan monoleate is measured the CMC of Herba Houttuyniae re-distilled liquid
The principle of polyoxyethylene sorbitan monoleate solubilising is that the polyoxyethylene sorbitan monoleate molecule forms so-called spherical or bar-shaped " micelle " in by solubilising solution, water-fast pharmaceutical pack is rolled in middle, form tens of materials to hundreds of Nano grade sizes, be dispersed in the water, make solution transparent, thereby reach the effect of dissolving.The polyoxyethylene sorbitan monoleate solubilising power has a crucial performance parameter-critical micelle concentration [CMC].The implication of CMC can play the minimum amount of solubilization.
When adding polyoxyethylene sorbitan monoleate in the medicinal liquid, the electrical conductivity of medicinal liquid can change along with the change of polyoxyethylene sorbitan monoleate consumption.When reaching CMC, rapid variation can take place in the electrical conductivity of medicinal liquid, produces a flex point that significantly rises, and by measuring electrical conductivity, draws polyoxyethylene sorbitan monoleate consumption-electrical conductivity curve, and the flex point of curve correspondence is exactly CMC.
Get the Herba Houttuyniae re-distilled liquid 50ml in the embodiment of the invention 1, drip polyoxyethylene sorbitan monoleate with microsyringe, every once, measures electrical conductivity after the stirring and dissolving, draws polyoxyethylene sorbitan monoleate consumption-electrical conductivity curve, and the flex point of curve correspondence is exactly the CMC value.The CMC pH-value determination pH the results are shown in Table 7 as a result, accompanying drawing 1,2,3,4.
Table 7 different manufacturers polyoxyethylene sorbitan monoleate and Herba Houttuyniae re-distilled liquid CMC value
The result shows: the polyoxyethylene sorbitan monoleate of different manufacturers, CMC difference.
Polyoxyethylene sorbitan monoleate is actual consumption in the injection prescription, is benchmark with CMC, according to the difference of medicine, is about the 2-5 of CMC doubly.Select the high-purity polysorbate-80 for injection of Nanjing Weir for use, actual amount is: 0.1%-0.3%.
The screening of experimental example 5 polyoxyethylene sorbitan monoleate consumptions
(1) get Herba Houttuyniae re-distilled liquid 1000ml in the embodiment of the invention 1, get 300ml and be used for measuring content, 700ml is with 0.22 μ m filter element filtering, mensuration content in addition.
(2) get three parts of Herba Houttuyniae re-distilled liquids in the embodiment of the invention 1, every part of 1000ml, adding polyoxyethylene sorbitan monoleate respectively is 1g, 2.5g, 5g, stirs 10 minutes, gets 300ml and measures content; Remaining measures content with 0.22 μ m filter element filtering.Parallel doing 2 times.The polyoxyethylene sorbitan monoleate of different amounts is to the influence of Herba Houttuyniae re-distilled liquid content, the results are shown in Table 8 and Fig. 5.
The polyoxyethylene sorbitan monoleate of table 8 different amounts is to the influence of Herba Houttuyniae re-distilled liquid content
Annotate: isopropyl alcohol component A:4-methyl isophthalic acid-isopropyl-3-cyclohexene-1-alkoxide component B:2-(4-methyl-3-cyclohexenyl group)
Component C: borneol acetate component D: methylnonanone
Can reach a conclusion from above-mentioned Fig. 5 and table 8: component C content did not reduce by 51% after 1. the Herba Houttuyniae re-distilled liquid did not add the polyoxyethylene sorbitan monoleate Direct Filtration, the D constituent content reduces by 82%, illustrate that filtration (0.22 μ m filter element) makes component C, D content, particularly component D content has major part to be filtered, and component A, B content water solublity are bigger, so change little before and after filtering.2. after polyoxyethylene sorbitan monoleate added, component C, D content raise in various degree, illustrate that polyoxyethylene sorbitan monoleate plays certain solubilizing effect.3. the consumption of polyoxyethylene sorbitan monoleate is 0.25% o'clock, and solubilizing effect reaches more than 90%, illustrates that the polyoxyethylene sorbitan monoleate consumption of Nanjing Weir is at 0.25% o'clock, and solubilizing effect is obvious.
Safety research result shows: the consumption of Herba Houttuyniae injectio polyoxyethylene sorbitan monoleate is being safe below 0.3%.Therefore, the Bindery security result of study, selecting the consumption of polyoxyethylene sorbitan monoleate is 0.25%.
The solubilizing effect of experimental example 6 polyoxyethylene sorbitan monoleates and HP-relatively
1, method
Get the Herba Houttuyniae re-distilled liquid of the embodiment of the invention 1 preparation, select tween 80, two kinds of solubilizing agents of HP-to experimentize, add solubilizing agent, stir and make dissolving, 0.45 μ m filter element filtering, embedding.Filter (0.45 μ m filter element filtering) in contrast with re-distilled liquid, each sample 500ml.Serve as to investigate index with clarity, content, both solubilizing effects relatively.
2, result
Annotate: isopropyl alcohol component A:4-methyl isophthalic acid-isopropyl-3-cyclohexene-1-alkoxide component B:2-(4-methyl-3-cyclohexenyl group)
Component C: borneol acetate component D: methylnonanone
Annotate: Herba Houttuyniae re-distilled liquid content: component A:8.67ug/ml; B component: 2.14ug/ml;
Component C:2.62ug/ml; Component D:54.34ug/ml.
3, interpretation of result
From The above results, solubilizing agent mainly is to component D(methylnonanone) solubilizing effect is obvious, and is not obvious to component A, B component solubilizing effect.Numerical value with component D sees that (consumption: solubilizing effect 0.25%) is greater than HP-(consumption: solubilizing effect 0.4%) for tween 80.
The investigation of experimental example 7pH value influence
(1) investigation of pH value regulator kind
Get the about 1500ml of Herba Houttuyniae re-distilled liquid in the embodiment of the invention 1, be divided into 3 parts, every part of 500ml, the polyoxyethylene sorbitan monoleate of adding 0.25%.The scheme of pressing table 9 adds the pH value regulator, measures content, investigates the variation that adds pH value regulator front and back principal agent composition, and assay the results are shown in Table 10.
The different pH value regulator schemes of table 9 design
The above results shows that it is less to content influence to regulate pH value with 10% citric acid soln, so select for use 10% citric acid soln to make the pH value regulator.
(2) investigation in pH value interval
Get the about 2000ml of Herba Houttuyniae re-distilled liquid in the embodiment of the invention 1, the polyoxyethylene sorbitan monoleate of adding 0.25% and 0.7% sodium chloride.Be divided into 4 parts, every part of 500ml presses pH value 4.0-4.5, pH value 4.5-5.0, four interval adjusting pH value of pH value 5.0-5.5, pH value 5.5-6.0 respectively, embedding, sterilization.With reference to " influence factor's test " method among two appendix X of Chinese Pharmacopoeia version in 2005 IX C, placed 10 days down at 60 ℃, be to investigate index with the pH value, detect the variation of pH value.The results are shown in Table 11.
The interval high temperature of the different pH value of table 11 is investigated the back pH value
The result shows that the interval 5.0-6.0 product of pH value is more stable.
The screening of embodiment 8 sterilising conditions
Get the re-distilled liquid in the embodiment of the invention 1, add an amount of polyoxyethylene sorbitan monoleate and be prepared from.Investigate to select 121 ℃ 13 minutes, 32 minutes, 105 ℃ sterilizations of 115 ℃ of sterilizations 30 minutes are with F
0Value, character, content are for investigating index.Character, assay the results are shown in Table 12, and wherein the RSD value contains measured value and the not comparison of sterilization product for the sterilization product.
Table 12 different temperatures sterilization testing result
Conclusion as can be drawn from Table 12:
1. from assay result's RSD value, adopt the different temperatures sterilization, the variation of content is less (less than 10%) all.
2. the sterilizing parameter of process stipulation of the present invention is 115 ℃, 32 minutes, and F
0Value is greater than 8, and the microbial survival probability that meets big small-volume injection must not be higher than 10
-6(F
0The value〉8) requirement.
3. adopt 121 ℃ of 13 minutes sterilization F
0Value is 17.3, greater than 12, can consider the sterilizing parameter of infusion solutions product, but will continue to investigate its stability.
Therefore, sterilizing parameter is selected 115 ℃ for use, 32 minutes.
The screening of embodiment 9 depyrogenation conditions
The method of depyrogenation has ultrafiltration and activated carbon method, the present invention obtains is the Herba Houttuyniae re-distilled liquid and the micellelike solution that forms that mixes of polyoxyethylene sorbitan monoleate, molecule is big by (1～100nm), remove pyrogen with ultrafilter membrane (1-20nm) the part medicinal liquid also is removed, so can not take out pyrogen with ultrafilter membrane; And remove pyrogen with active carbon, will consider that active carbon is to the adsorption of medicinal liquid.
1, active carbon influences experiment to the prescription principal agent:
Get Herba Houttuyniae re-distilled liquid 430ml, mixing adds 0.25% polyoxyethylene sorbitan monoleate, stirs to make dissolving in 10 minutes; Add 0.7% sodium chloride, stir and made dissolving in 10 minutes.Stock solution sampling 10ml is numbered No. 1; Residue medicinal liquid 420ml is by following operation.
The residue medicinal liquid is equally divided into 3 parts, numbers No. 2-No. 4, adds 0.01% active carbon respectively, is heated to about 80-90 ℃, is incubated 10 minutes.Filter with the G4 sintered glass funnel, get filtrate, filtrate is transferred in the wide mouthed bottle of depyrogenation, sealing, standby.Press the Herba Houttuyniae injectio determination, measure content, the results are shown in Table 13.
Table 13 pair prescription drug content influence
Above result shows that 0.01% active carbon is big to the adsorption of the content of Herba Houttuyniae re-distilled liquid, and it is more than half that its content is descended.Illustrate that to add active carbon very big to the influence of content, so the present invention does not add active carbon and removes pyrogen.
(2) control pyrogen by bacterial endotoxin (bacterial endotoxin is lower than 0.5EU/ml) and the production process microbial contamination of control re-distilled liquid, adjuvant, intermediate, 5 batches of products of pilot scale are also verified, be the results are shown in Table 14.
Table 145 crowd production sample bacterial endotoxin checking result
The above results shows: by the bacterial endotoxin of control Herba Houttuyniae re-distilled liquid, adjuvant, Herba Houttuyniae injectio intermediate, the finished product pyrogen test meets the requirements.
Embodiment 10 polymer substance inspections
The present invention be bright Herba Houttuyniae through the formulated preparation of the re-distilled liquid of second distillation gained, do not have polymer substance in order to confirm product, product is carried out polymer substance inspections such as protein, tannin, resin.Inspection method is as follows:
(an appendix IX of Chinese Pharmacopoeia version in 2010 S) carries out protein, tannin, resin inspection according to injection related substance inspection technique:
Protein is got the embodiment of the invention 1 described injection 1ml, adds 30% sulfosalicylic acid test solution 1ml of new preparation, and mixing was placed 5 minutes, muddiness must not occur.
Tannin is got the embodiment of the invention 1 described injection 1ml, adds the normal saline 5ml that contains 1% Ovum Gallus domesticus album of new preparation, places 10 minutes, muddiness or precipitation must not occur.
Resin is got the embodiment of the invention 1 described injection 5ml, adds 1 of hydrochloric acid, places 30 minutes, precipitation must not occur.
The embodiment of the invention 1 described injection is carried out polymer substance check results such as protein, tannin, resin see Table 15.
Table 15 polymer substance assay
Check result shows: 6 batch samples all do not detect protein, tannin, resin, by existing production technology production, do not have polymer substance in the product.
The rate of transform of embodiment 11 Herba Houttuyniae medical material-finished products
1, carry out middle trial production according to the embodiment of the invention 1 described process conditions, pilot scale is 25-40 ten thousand ml in batches, and totally 10 batches, the rate of transform of calculating Herba Houttuyniae medical material-finished product is as table 16.
The rate of transform of table 16 Herba Houttuyniae medical material-finished product
Measurement result shows:
(1) Herba Houttuyniae medical material-finished product mean transferred rate is component A57.2%, B component 63.5%, component C4.6%, component D3.4%, and is consistent with Herba Houttuyniae medical material-re-distilled liquid mean transferred rate.
(2) though the content difference of medical material is bigger, less according to the finished product content differences between batches that the existing production technology of determining is produced, the steady quality homogeneous proves that the embodiment of the invention 1 described production technology can guarantee the constant product quality homogeneous.
2, re-distilled liquid-finished product rate of transform
Carry out middle trial production according to the embodiment of the invention 1 described process conditions, pilot scale is 25-40 ten thousand ml in batches, and totally 10 batches, the rate of transform of calculating re-distilled liquid-finished product sees Table 17.
The rate of transform of table 17 re-distilled liquid-finished product
Measurement result shows:
(1) re-distilled liquid-finished product mean transferred rate is component A99.5%, B component 114.0%, component C91.3%, component D80.6%.
(2) the content rate of transform of B component has surpassed 100%, may be in the preparation process conversion to have taken place.
(3) make little pin with a collection of re-distilled liquid and the jumbo rate of transform of infusion solutions is lower, reason may be too little in batches due to.
Following embodiment all can realize the effect of above-mentioned experimental example.
The specific embodiment
Embodiment 1
(1) is that 1:2 gets 2000 kilograms in top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture according to mass ratio, carries out vapor distillation, collect just 2000 liters of distillates, carry out redistillation again, collect 1000 liters of re-distilled liquids;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 10 minutes, adds 7 kilograms of sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
Embodiment 2
(1) is that 1:3 gets 2000 kilograms in top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture according to mass ratio, carries out vapor distillation, collect just 1500 liters of distillates, carry out redistillation again, collect 850 liters of re-distilled liquids;
(2) adding by weight/volume in the re-distilled liquid is 2.9 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 8 minutes, adds 7 kilograms of sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
Embodiment 3
(1) is that 1:1.5 gets 2000 kilograms in top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture according to mass ratio, carries out vapor distillation, collect just 2500 liters of distillates, carry out redistillation again, collect 1300 liters of re-distilled liquids;
(2) adding by weight/volume in the re-distilled liquid is 2.6 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 15 minutes, adds 7 kilograms of sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
Embodiment 4
(1) is that 1:2 gets 2000 kilograms in top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture according to mass ratio, carries out vapor distillation, collect just 2000 liters of distillates, carry out redistillation again, collect 1000 liters of re-distilled liquids;
(2) adding by weight/volume in the re-distilled liquid is 2.7 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 kilograms of sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
Embodiment 5
(1) is that 1:2 gets 2000 kilograms in top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture according to mass ratio, carries out vapor distillation, collect just 2000 liters of distillates, carry out redistillation again, collect 1000 liters of re-distilled liquids;
(2) adding by weight/volume in the re-distilled liquid is 2.9 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 kilograms of sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
Embodiment 6
(1) is that 1:2 gets 2000 kilograms in top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture according to mass ratio, carries out vapor distillation, collect just 2000 liters of distillates, carry out redistillation again, collect 1000 liters of re-distilled liquids;
(2) adding by weight/volume in the re-distilled liquid is 3 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 kilograms of sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
Embodiment 7
(1) is that 1:1.5 gets 2000 kilograms in top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture according to mass ratio, carries out vapor distillation, collect just 2000 liters of distillates, carry out redistillation again, collect 1000 liters of re-distilled liquids;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 kilograms of sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
Embodiment 8
(1) is that 1:2.5 gets 2000 kilograms in top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture according to mass ratio, carries out vapor distillation, collect just 2000 liters of distillates, carry out redistillation again, collect 1000 liters of re-distilled liquids;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 kilograms of sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
Claims (19)
1. the preparation method of a Herba Houttuyniae injectio is characterized in that this method comprises the steps:
(1) be that 1:1-3.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carry out vapor distillation, collect distillate 1000-3000 parts by volume just, carry out redistillation again, collect re-distilled liquid 700-1300 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰-3 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃;
Wherein, between above-mentioned weight portion and the parts by volume be the relation of g/ml.
2. preparation method as claimed in claim 1 is characterized in that this method comprises the steps:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) by weight/volume is 2.5 ‰ polyoxyethylene sorbitan monoleate in the re-distilled liquid, stirs and makes dissolving in 10 minutes, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and it is 5.0-6.0 that the citric acid soln with 10% is regulated pH value;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
3. preparation method as claimed in claim 1 is characterized in that this method comprises the steps:
(1) is that 1:3 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 1500 parts by volume just, carry out redistillation again, collect re-distilled liquid 850 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.9 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 8 minutes, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
4. preparation method as claimed in claim 1 is characterized in that this method comprises the steps:
(1) is that 1:1.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2500 parts by volume just, carry out redistillation again, collect re-distilled liquid 1300 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.6 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 15 minutes, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
5. preparation method as claimed in claim 1 is characterized in that this method comprises the steps:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.7 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
6. preparation method as claimed in claim 1 is characterized in that this method comprises the steps:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.9 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
7. preparation method as claimed in claim 1 is characterized in that this method comprises the steps:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 3 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
8. preparation method as claimed in claim 1 is characterized in that this method comprises the steps:
(1) is that 1:1.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
9. preparation method as claimed in claim 1 is characterized in that this method comprises the steps:
(1) is that 1:2.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
10. a Herba Houttuyniae injectio is characterized in that preparing by claim 1-9 method.
11. Herba Houttuyniae injectio as claimed in claim 10 is characterized in that this Herba Houttuyniae injectio prepares by the following method:
(1) be that 1:1-3.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carry out vapor distillation, collect distillate 1000-3000 parts by volume just, carry out redistillation again, collect re-distilled liquid 700-1300 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰-3 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃;
Wherein, between above-mentioned weight portion and the parts by volume be the relation of g/ml.
12. Herba Houttuyniae injectio as claimed in claim 10 is characterized in that this Herba Houttuyniae injectio prepares by the following method:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) by weight/volume is 2.5 ‰ polyoxyethylene sorbitan monoleate in the re-distilled liquid, stirs and makes dissolving in 10 minutes, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and it is 5.0-6.0 that the citric acid soln with 10% is regulated pH value;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
13. Herba Houttuyniae injectio as claimed in claim 10 is characterized in that this Herba Houttuyniae injectio prepares by the following method:
(1) is that 1:3 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 1500 parts by volume just, carry out redistillation again, collect re-distilled liquid 850 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.9 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 8 minutes, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
14. Herba Houttuyniae injectio as claimed in claim 10 is characterized in that this Herba Houttuyniae injectio prepares by the following method:
(1) is that 1:1.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2500 parts by volume just, carry out redistillation again, collect re-distilled liquid 1300 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.6 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 15 minutes, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
15. Herba Houttuyniae injectio as claimed in claim 10 is characterized in that this Herba Houttuyniae injectio prepares by the following method:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.7 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
16. Herba Houttuyniae injectio as claimed in claim 10 is characterized in that this Herba Houttuyniae injectio prepares by the following method:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.9 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
17. Herba Houttuyniae injectio as claimed in claim 10 is characterized in that this Herba Houttuyniae injectio prepares by the following method:
(1) is that 1:2 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 3 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
18. Herba Houttuyniae injectio as claimed in claim 10 is characterized in that this Herba Houttuyniae injectio prepares by the following method:
(1) is that 1:1.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
19. Herba Houttuyniae injectio as claimed in claim 10 is characterized in that this Herba Houttuyniae injectio prepares by the following method:
(1) is that 1:2.5 gets top, fresh fish raw meat meadow and Herba Houttuyniae under ground portion mixture 2000 weight portions according to mass ratio, carries out vapor distillation, collect distillate 2000 parts by volume just, carry out redistillation again, collect re-distilled liquid 1000 parts by volume;
(2) adding by weight/volume in the re-distilled liquid is 2.5 ‰ polyoxyethylene sorbitan monoleate, stirs and makes dissolving in 5-20 minute, adds 7 weight portion sodium chloride, stirs and makes dissolving in 10 minutes, and the citric acid soln adjusting pH value with 10% is 5.0-6.0;
(3) to the re-distilled liquid after step (2) processing, use the filter element of 0.45 μ m and 0.22 μ m to filter, embedding was sterilized 32 minutes, and was namely got Herba Houttuyniae injectio for 115 ℃.
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| CN2013101690974A CN103239395A (en) | 2011-07-21 | 2011-07-21 | Houttuynia cordata injection and preparation method thereof |
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| CN2013101690974A CN103239395A (en) | 2011-07-21 | 2011-07-21 | Houttuynia cordata injection and preparation method thereof |
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| CN 201110205127 Division CN102266420B (en) | 2011-07-21 | 2011-07-21 | Method for preparing heartleaf houttuynia herb injection |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| CN115300561A (en) * | 2022-09-06 | 2022-11-08 | 四川梓鸿生物技术有限公司 | Houttuynia injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110903905A (en) * | 2019-11-07 | 2020-03-24 | 湖南正清制药集团股份有限公司 | Remote control system for preparing houttuynia volatile oil and saturated aromatic water |
| CN115300561A (en) * | 2022-09-06 | 2022-11-08 | 四川梓鸿生物技术有限公司 | Houttuynia injection and preparation method thereof |
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