CN102885932A - Heartleaf houttuynia herb injection and preparation method thereof - Google Patents
Heartleaf houttuynia herb injection and preparation method thereof Download PDFInfo
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Abstract
The invention provides a heartleaf houttuynia herb injection and a preparation method thereof. The method comprises the following steps of: preparing distillate by using a certain quantity of fresh heartleaf houttuynia herb medicinal material through a steam distillation method; and adding accessories, lacking bacteria at the temperature of 115 DEG C for 32 minutes to obtain an injection, wherein the preservation condition of the fresh heartleaf houttuynia herb medicinal material is that: the collected heartleaf houttuynia herb medicinal material is stored at the temperature of not more than 30 DEG C for not more than 28 hours.
Description
Technical field
The present invention relates to the field of Chinese medicines, be specifically related to a kind of Herba Houttuyniae injectio and preparation method thereof.
Background technology
Herba Houttuyniae is the herb of Chinese medicine Saururaceae herbaceos perennial Herba Houttuyniae (Howtingria cordata Thanb).Modern pharmacy studies show that it contains the volatile ingredients such as certain herbaceous plants with big flowers acyl acetaldehyde, lauryl aldehyde, bornene, myrcene and methylnonanone.Traditional medicine thinks that its stem and leaf can be used as medicine, cold nature, and acrid in the mouth is returned lung meridian, has heat-clearing and toxic substances removing, the detumescence toxin expelling, the effect of inducing diuresis for treating stranguria syndrome cures mainly that lung abscess vomiting pus, expectorant heat syndrome cough are breathed heavily, hematodiarrhoea pyretic stranguria, carbuncle sore tumefacting virus etc.Herba Houttuyniae is conventional medicament in Chinese medicine already.
In recent years, people conduct in-depth research for Herba Houttuyniae, and develop the injection dosage form of Herba Houttuyniae.
As far back as the sixties in last century, China scientific and technical personnel namely begin the development of Houttuynia cordata injection, the use of succeeding in developing the seventies and go on the market.This medicine is common antimicrobial agents, has the advantage such as do not develop immunity to drugs, cheap, also is the typical case that Chinese medicine develops into the modern Chinese medicine preparation.This medicine at antiviral, the aspect curative effect such as bring down a fever is reliable, speed is fast, is called as " Chinese medicine antibiotic ".
Ministry of Public Health standard (WS3-B-3264-98) discloses the preparation method of Herba Houttuyniae injectio, namely " get bright Herba Houttuyniae 2000g and carry out vapor distillation, collect just distillate 2000ml, carry out again redistillation; collect the about 1000ml of re-distilled liquid; add 7g sodium chloride and 5g polyoxyethylene sorbitan monoleate, mixing injects water and makes into 1000ml; filter; embedding, sterilization, and get final product.”
Herba Houttuyniae injectio becomes clinical anti-infective critical treatment medicine gradually because curative effect is outstanding.But along with being widely used, the report of its untoward reaction also is on the increase.
The untoward reaction case report with injections such as Herba Houttuyniae injectio of receiving from national drug adverse reaction monitoring central database.Main serious adverse reaction shows as anaphylactic shock, systemic anaphylaxis and dyspnea etc., and has death to occur.Mainly comprise skin and systemic anaphylaxis, clinical manifestation is erythra, strip off dermatitis; Cough, xerostomia, tachypnea, dyspnea, acute lung edema; Feel sick, vomit; Anaphylactic shock, allergic asthma, laryngeal edema etc.(connect clean steel, Xue Peihua, Kong Defeng is etc. Herba Houttuyniae injectio 2 examples that cause allergic reaction. adverse effect magazine, 2001,3 (3): 198-20)
It is reported that the every annual value of production of Herba Houttuyniae injectio is about 8,500,000,000 yuan, injection in 2005 person-time reaches 600,000,000.In June, 2006, State Food and Drug Administration has halted 7 injection kinds such as Herba Houttuyniae injectio, and 195 the Herba Houttuyniae drug for injection manufacturing enterprises in the whole nation are 2,000,000,000 yuan of 06 year estimated losses.Its most serious problem is the anaphylactic shock acute death.
Studies show that Chinese crude drug goes mouldy owing to the reasons such as ambient temperature, humidity produce, and not only affects the wherein content of effective ingredient, but also can produce toxin, causes the untoward reaction of product in storage and transport process.
So far, also there is not a kind of good way can effectively solve the problem that Herba Houttuyniae injectio causes untoward reaction.
Summary of the invention
The object of the invention is, overcomes the defective of prior art, and a kind of Herba Houttuyniae injectio is provided, and this injection has the advantages such as preparation stabilization, untoward reaction be low.
Another purpose of the present invention has been to provide the preparation method of this Herba Houttuyniae injectio.
Adopt following method to be prepared from:
Get a certain amount of fresh Herba Houttuyniae, adopt twice steam distillation to prepare distillate: with fresh Herba Houttuyniae with vapor distillation after, with the distillate redistillation that obtains, obtain re-distilled liquid again; Add polyoxyethylene sorbitan monoleate and sodium chloride, mix homogeneously adds the water for injection adjusted volume, filter, and embedding, sterilization is prepared into injection; Wherein, the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 28 hours.
Preferably, adopt following method to be prepared from:
Get a certain amount of fresh Herba Houttuyniae, adopt twice steam distillation to prepare distillate: the distillate that first distillation extraction obtains is 1: 0.5～1.5 with the volume/mass of fresh Herba Houttuyniae than (v/w), and the re-distilled liquid that redistillation extracts amasss with fresh fish raw meat cursive script/and mass ratio (v/w) is 1: 1.5～2.5; The sodium chloride that adds the polyoxyethylene sorbitan monoleate and 0.3%～0.45% (according to the weighing scale of Herba Houttuyniae) of 0.05%～0.2% (according to the weighing scale of Herba Houttuyniae), mix homogeneously, add the water for injection adjusted volume, filter, embedding, sterilized 8～40 minutes, and be prepared into injection for 110 ℃～121 ℃; Wherein, the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 26 hours.
Most preferred, adopt following method to be prepared from:
Get a certain amount of fresh Herba Houttuyniae, adopt twice steam distillation to prepare distillate: the distillate that first distillation extraction obtains is 1: 1 with the volume/mass of fresh Herba Houttuyniae than (v/w), and the re-distilled liquid that redistillation extracts amasss with fresh fish raw meat cursive script/and mass ratio (v/w) is 1: 2; The sodium chloride that adds the polyoxyethylene sorbitan monoleate and 0.35% (according to the weighing scale of Herba Houttuyniae) of 0.125% (according to the weighing scale of Herba Houttuyniae), mix homogeneously adds the water for injection adjusted volume, filter, embedding was sterilized 32 minutes, and was prepared into injection for 115 ℃; Wherein, the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 24 hours.
Need to prove, the mass ratio that above product described " volume/mass is than (v/w) " is volume and the fresh Herba Houttuyniae of distillate, unit is respectively volume (L)/quality (kg), perhaps volume (ml)/quality (g).
Described polyoxyethylene sorbitan monoleate satisfies following requirement:
Color is colourless to faint yellow, acid number≤2.0, and saponification number is 45～55, acid-base value is 5.0～7.5, moisture≤1.0%, residue on ignition≤0.15%, peroxide value≤10, arsenic salt≤0.0002%, myristic acid≤1.0%, Palmic acid≤2.0%, palmitoleic acid≤1.0%, stearic acid≤2.0%, oleic acid 〉=90.0%, linoleic acid≤3.0%, linolenic acid≤1.0%, oxirane≤0.0001%, dioxane≤0.001% contains endotoxic amount less than 0.6EU among every 1mg, haemolysis and coagulation: it is an amount of to get this product, accurately weighed, add solution that water makes 6mg/ml as test liquid, must not haemolysis.
In the Herba Houttuyniae injectio of the present invention, be equivalent to Herba Houttuyniae crude drug amount 2g in every 1ml injection.
The preparation method of a kind of safer Herba Houttuyniae injectio of the present invention is comprised of following steps:
Get a certain amount of fresh Herba Houttuyniae, adopt twice steam distillation to prepare distillate: with fresh Herba Houttuyniae with vapor distillation after, with the distillate redistillation that obtains, obtain re-distilled liquid again; Add polyoxyethylene sorbitan monoleate and sodium chloride, mix homogeneously adds the water for injection adjusted volume, filter, and embedding, sterilization is prepared into injection; Wherein, the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 28 hours.
Preferably, formed by following steps:
Get a certain amount of fresh Herba Houttuyniae, adopt twice steam distillation to prepare distillate: the distillate that first distillation extraction obtains is 1: 0.5～1.5 with the volume/mass of fresh Herba Houttuyniae than (v/w), and the re-distilled liquid that redistillation extracts amasss with fresh fish raw meat cursive script/and mass ratio (v/w) is 1: 1.5～2.5; The sodium chloride that adds the polyoxyethylene sorbitan monoleate and 0.3%～0.45% (according to the weighing scale of Herba Houttuyniae) of 0.05%～0.2% (according to the weighing scale of Herba Houttuyniae), mix homogeneously, add the water for injection adjusted volume, filter, embedding, sterilized 8～40 minutes, and be prepared into injection for 110 ℃～121 ℃; Wherein, the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 26 hours.
Most preferred, formed by following steps:
Get a certain amount of fresh Herba Houttuyniae, adopt twice steam distillation to prepare distillate: the distillate that first distillation extraction obtains is 1: 1 with the volume/mass of fresh Herba Houttuyniae than (v/w), and the re-distilled liquid that redistillation extracts amasss with fresh fish raw meat cursive script/and mass ratio (v/w) is 1: 2; The sodium chloride that adds the polyoxyethylene sorbitan monoleate and 0.35% (according to the weighing scale of Herba Houttuyniae) of 0.125% (according to the weighing scale of Herba Houttuyniae), mix homogeneously adds the water for injection adjusted volume, filter, embedding was owed bacterium 32 minutes, and was prepared into injection for 115 ℃; Wherein, the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 24 hours.
Need to prove, the mass ratio that above method described " volume/mass is than (v/w) " is volume and the fresh Herba Houttuyniae of distillate, unit is respectively volume (L)/quality (kg), perhaps volume (ml)/quality (g).
In the Herba Houttuyniae injectio of the present invention, be equivalent to Herba Houttuyniae crude drug amount 2g in every 1ml injection.
Described polyoxyethylene sorbitan monoleate satisfies following requirement:
Color is colourless to faint yellow, acid number≤2.0, and saponification number is 45～55, acid-base value is for being 5.0～7.5, moisture≤1.0%, residue on ignition≤0.15%, peroxide value≤10, arsenic salt≤0.0002%, myristic acid≤1.0%, Palmic acid≤2.0%, palmitoleic acid≤1.0%, stearic acid≤2.0%, oleic acid 〉=90.0%, linoleic acid≤3.0%, linolenic acid≤1.0%, oxirane≤0.0001%, dioxane≤0.001% contains endotoxic amount less than 0.6EU among every 1mg, haemolysis and coagulation: it is an amount of to get this product, accurately weighed, add solution that water makes 6mg/ml as test liquid, must not haemolysis.
Chinese crude drug must experience the stages such as storage and transportation from producing to use.In this process, because the variation of condition of storage can cause going mouldy of medical material even affect the wherein content of effective ingredient.Therefore, the degraded of medicine self material of initiation is the one of the main reasons that affects the Herba Houttuyniae injectio safe handling always because medical material goes mouldy.
The present invention is directed to the characteristics of Herba Houttuyniae, selected the holding conditions of fresh Herba Houttuyniae.The result shows that the Herba Houttuyniae that GAP gathers in the base, storage time are no more than 24 hours, and reserve temperature is no more than 30 ℃.Adopt the Herba Houttuyniae injectio steady quality of the fresh Herba Houttuyniae preparation that the method obtains, use safer, more stable, have no side effect.
Secondly, the reaction of Herba Houttuyniae injectio toxic is also closely related with the adjuvant that wherein contains.[the Lei Lei such as Lei Lei, Pu XuFeng, Yang Kui etc.], the experimentation 1-dog intravenously administrable untoward reaction research of Herba Houttuyniae injectio intravenously administrable untoward reaction, herbal pharmacology is in clinical, 2007,23 (5): 131-133] find, the dog vein give with Herba Houttuyniae injectio, polyoxyethylene sorbitan monoleate sodium chloride injection after the serious adverse reactions such as agitation, skin pruritus, face and skin erythema all appearred in 10 minutes.
For this problem, the present invention is by adjusting the storage condition of Herba Houttuyniae, so that Herba Houttuyniae is more stable, guaranteed better the quality of product from the source.
Simultaneously, the consumption by large quantity research minimizing polyoxyethylene sorbitan monoleate reduces the Herba Houttuyniae injectio adverse reaction rate to greatest extent.
And, by the quality of control polyoxyethylene sorbitan monoleate behind the large quantity research, so that the quality of Herba Houttuyniae injectio of the present invention has further obtained better effect.Comprise:
(1) prescription of high oleic acid: make the content of oleic acid in the oleic acid raw material surpass 90%, form the requirement that high oleic acid forms under the detection to satisfy the product fatty acid, reduce the content of non-oleic acid component, the oleic acid of product forms the requirement that can satisfy European Pharmacopoeia, has effectively avoided because of the impact of oleic acid mass change on product purity.
(2) prescription of raising sorbitol anhydride: by the improvement of production technology, improved the content of sorbitol anhydride, reduced the moisture content amount, reduced dextranomer content, the raw material color and luster is shoaled.
(3) adopt superb ethoxylation technology, product molecular weight distribution is narrow, and the harmful substance such as oxirane and diox is residual almost nil in the product, meets American-European standards of pharmacopoeia.
(4) adopt high-efficient esterified catalyst, conversion rate of esterification is high, and product color is shallow, need not chemical decolorization (hydrogen peroxide) and processes, and peroxide value reaches standards of pharmacopoeia easily, and safety is better.
(5) aseptic, the apyrogeneity control of production process meet the basic demand of injection supplementary material.
On this basis, with reference to the EP standard, set up the quality standard of polyoxyethylene sorbitan monoleate, increased the control of content of fatty acid and the limit examine of oxirane and dioxane.Significantly improved the quality of polyoxyethylene sorbitan monoleate.
Test example one bright Herba Houttuyniae storage time and condition are further studied
1 experiment purpose
By this research, fresh Herba Houttuyniae to freshly harvested adopts different time and conditions to preserve, and by outward appearance situation of change in the whole storage of Herba Houttuyniae is observed, measure bright Herba Houttuyniae different storage period of index component content and conclude and cause rotten microbe sort storage period, substantially make index composition Changing Pattern in the Herba Houttuyniae storage clear, affect the principal element of Herba Houttuyniae quality in the storage, and look for effective ways to its control, thereby guarantee the controlled of Herba Houttuyniae storage, for best storage period and the best storage requirement of determining bright Herba Houttuyniae provides foundation, in the hope of with provenance, cultivation, field management, the research such as gather forms a complete research chain.
2 experiment contents
To Herba Houttuyniae gather, the outward appearance situation of change is observed in the processing, storage process; Adopt gas chromatography that the index composition is detected; Take bright Herba Houttuyniae as object of study, carry out the research of microorganism situation of change for the Herba Houttuyniae that rots in the storage, determine in the Herba Houttuyniae storage, to cause the classification of rotten microorganism.
3 experimental techniques
3.1 sampling method
For the accuracy that guarantees to test, whole experiment is carried out three times repeat.Each experiment is excavated time, weather conditions, storage place, period of storage, index component content detection sampling numbering and Experiment on Microbiology to Herba Houttuyniae and is done respective record sample time, sees Table 1.
Sampling experimental record table is excavated in table 1 experiment
3.2 the observation of appearance character
Gather, process, in the transportation, storage process, respectively after gathering, after the processing, after the transportation and carry out appearance character in the storage and observe, observed once every 12 hours in the storage, the each observation carried out corresponding appearance character record and collection of photos, simultaneously the variations in temperature at stockpile middle part in the storage monitored.
3.3 the mensuration of heap internal and external temperature in the storage process
When each assay is taken a sample in the storage process, temperature and out-pile temperature in the sampling heap are measured record.
3.4 the index component content detects
Carry out when appearance character observes above-mentioned, 4-methyl isophthalic acid-isopropyl-3-cyclohexene-1-alcohol, 2-(4-methyl-3-is hexenyl not) isopropyl alcohol, 3 index component contents detections of methylnonanone are carried out in sampling, sample is got from the Herba Houttuyniae that sign is arranged at random, each sampling amount is 1kg, and be that Herba Houttuyniae is when occurring rotting the deadline of sampling.In order to guarantee actual response sample size situation of change, the sample of getting in the base extracts at the base laboratory.
3.5 the rotten research that causes microorganism
Different parts is got rotten sample from heap, carry out first the preliminary judgement of outward appearance symptom by rotting which quasi-microorganism causes, then cut the strong section of disease intersection tissue, sample preparation, use microscopic examination, what germ rotting preliminary judgement is by, further causes separation and the Identification of Species of rotten bacterium again.
4 experimental results and analysis
4.1 bright Herba Houttuyniae appearance character storage period is analyzed
Bright Herba Houttuyniae in the storage process every 12 hours, is carried out appearance character and observes, and the observed and recorded content of three repetitions sees Table 2.
The bright Herba Houttuyniae of table 2 appearance character storage period is observed
As can be seen from Table 2,3 storage periods, appearance character observation experiment result all showed: bright Herba Houttuyniae is stored 24 hours without yellow leaf and is rotted, and compares comparatively fresh; Stored 36 hours, and a small amount of yellow leaf occurred; Storing had rotten leaf to occur in 48 hours; It is more obvious to store 60 hours rotten situations of blade, and putrefactive phenomenon also appears in rhizome section.Stack in 60 hours that observe in storage, the fresh fish raw meat grass under ground portion that repeats in 1 occurs without rotten symptom.
4.2 the mensuration of heap internal and external temperature in the storage process
To in the storage process during each assay sampling in the heap and in the heap temperature do to measure record, record data see Table 3:
The heap internal and external temperature is measured log in table 3 storage process
Put from fresh fish raw meat haystack and to begin to survey temperature and temperature in the heap 12 hours, as can be seen from Table 3, from 12nd hour, temperature is apparently higher than the temperature of same time in the heap, and along with the increase of storage time, the temperature difference is increasing, even can reach 20 ℃, tracing it to its cause one is that the heat that distributes is difficult for scattering and disappearing in the heap, the 2nd, and along with the increase of saprophytic property microorganism, these microbial metabolisms also can release heat make that temperature raises in the heap.
4.3 bright Herba Houttuyniae different time sections storage period index component content is analyzed
Bright Herba Houttuyniae different time storage period 4-methyl isophthalic acid-isopropyl-3-cyclohexene-1-alcohol, 2-(4-methyl-3-cyclohexenyl group) isopropyl alcohol, 3 kinds of index component contents of methylnonanone are measured, are detected data and see Table 4:
Three experimental index composition detection of table 4 data record
Can find out from above-mentioned table 2,3,4 data: 4-methyl isophthalic acid-isopropyl-3-cyclohexene-1-alcohol presents the variation tendency of " falling first rear liter ", and namely the passing along with storage time in front 48 hours, content was reduced to minimumly on the 48th hour, raise again afterwards; The trend of 2-(4-methyl-3-cyclohexenyl group) isopropanol content general performance for reducing; The content of methylnonanone then general performance is the variation tendency of " fall after rising again rise ", storage height when content was than the 12nd hour during by 24 hours, 36 hours, and content drops to minimumly time the 48th hour, stores that content raises again after 60 hours.
(repetition 2 and repetition 3) is analyzed to different storage conditions, when the storage same time, 3 indexs all show as repetition 3 ratios and repeat 2 content height, mainly are possible be that the holding conditions of repetition 2 is open-air because repeating 3 is to preserve under shady and cool condition.
4.3 bright Herba Houttuyniae causes rotten microbe species and identifies
Through causing rotten reason just declare, cause rotten bacterium separate, cause rotten strain class identify, separate the saprogenicity of pathogenic bacterium is measured and temperature on causing several steps such as impact of rotten bacteria growing, draw and cause in three repetitions that fresh fish raw meat Fructus Fragariae Ananssae becomes, rotten reason, and identified and cause rotten microbe species, see Table 5.
Table 5 fresh fish raw meat Fructus Fragariae Ananssae becomes, the reason of rotting and cause rotten microbe species
For the first time having repeated to determine to cause the maize ear rot indigenous bacteria is the carrot soft rot Erwinia (Erwiniacarotovora) that erwinia belongs to.According to reported in literature, the cause harm kind of plant of this bacterium is a lot, is that plants and plant product causes rotten main pathogen antibacterial in transportation and storage, causes rotten antibacterial and can adapt to the interior higher temperature of outdoor heap, and cause rotten.
Experiment has determined to cause the maize ear rot fungal pathogens for the second time five kinds, cause that wherein what go mouldy mainly is to be glaucous aspergillus sydowi, these five kinds of funguses are except the southern blight bacterium, all the other several funguses all are very strong saprophytic property funguses, can cause the fungus that a lot of vegetable materials go mouldy in transporting procedures.
Experimental identification goes out to cause that the Herba Houttuyniae rotten actinomycetes that go mouldy are two kinds of actinomycetes of streptomyces for the third time: leucosporae group actinomycetes and suction monoid actinomycetes, the former mainly causes rotten actinomycetes, these two kinds of actinomycetes happiness higher temperatures.
This shows, cause that the microbe species that rots of bright Herba Houttuyniae is complicated, just different under different temperature and humidity conditions, cause that rotten dominant microflora is different.
5 conclusions
Repeat for 3 times to storage period bright Herba Houttuyniae appearance character observed result show: bright Herba Houttuyniae is stored 24 hours without yellow leaf and rotten, compares comparatively fresh; Stored 36 hours, and a small amount of yellow leaf occurred; Storing had rotten leaf to occur in 48 hours.
In repeating for 3 times, bright Herba Houttuyniae 2-(4-methyl-3-cyclohexenyl group) isopropyl alcohol presents different variation tendencies with methylnonanone 3 lattice index component contents in storage process, but content is minimum when all showing as the 48th hour, presents afterwards the trend of rising.
To in causing that pathogenic bacteria that bright Herba Houttuyniae rots is analyzed, can find out that antibacterial, fungus and more actinomycetic kinds all can cause rotting of Herba Houttuyniae, different gather and storage condition under, cause that rotten dominant microflora is different.By 3 classes are caused rotten bacterium to the analysis of responsive to temperature degree, except southern blight bacterium (being that Herba Houttuyniae field disease is normal), all the other pathogenic bacterias all grow best about 35 ℃, and this is also consistent with about 35 ℃ symptoms that occur rotting of the interior temperature of heap in the Herba Houttuyniae storage.
In the storage of bright Herba Houttuyniae, integrated appearance character, content and cause rotten microbiological analysis, in order to guarantee the quality of Herba Houttuyniae, the gathering of Herba Houttuyniae should be chosen in fine day or the cloudy day carries out, and avoids gathering in rainy day and the fine situation that dew arranged; Should shady and cool storage after gathering, stacking in the storage can not tension, and temperature can not be too high in the heap, preferably is controlled at below 30 ℃; For fear of causing rotten microorganism fresh fish raw meat herbaceous stem amount is impacted, bright Herba Houttuyniae storage time should not be above 24 hours.
Simultaneously, the used crude drug of a kind of Herba Houttuyniae injectio of the present invention has adopted the Herba Houttuyniae storage procedures of adjusting, and has guaranteed the stable of Herba Houttuyniae, and then has made its injection products steady quality, reduce heat source response, greatly reduced the untoward reaction in the clinic trial process.
Test example two Herba Houttuyniae herbs storage is on the research of Herba Houttuyniae injectio end product quality impact
1, experiment purpose
By to the research of bright Herba Houttuyniae herb storage to Herba Houttuyniae injectio end product quality mark sound, determine to keep temperature in best critical storage time and the heap.
2, experimental procedure
(1) gets respectively harvesting 12h, 24h, 36h, 48h, keep temperature to be respectively 25 ℃, 30 ℃, 35 ℃ Herba Houttuyniae raw material in the heap, make injection according to the method for embodiment 1.
(2) according to standards of pharmacopoeia, measure each quality index of Herba Houttuyniae injectio.
3, experimental result
To 12 groups of experiment Herba Houttuyniae injectio of qualified finished product Herba Houttuyniae injectio and design, according to " the Chinese pharmacopoeia standard testing result sees Table 6.
4, conclusion
Can draw to draw a conclusion from table 6 research:
1, holding time and storage temperature have a great impact Herba Houttuyniae injectio part quality standard.
2, raw material is interiorly preserved under the state below 30 ℃ at heap, and at front 24 hours, it is substantially constant that pH value keeps, but preserve under 35 ℃ of states, and descending appears in pH value; After 36 hours, pH value begins to descend; When wherein piling 35 ℃ of lower storages of interior temperature, by 48 hours, pH value dropped to defective at storage.May be that the some chemical properties group decomposes in the Herba Houttuyniae because along with the growing of antibacterial, the production VFA causes pH value to decrease.
3, measure from content of monomer.48 hours product of raw material storage, 4-methyl isophthalic acid-isopropyl-3-cyclohexene-1-alcohol content is substantially defective; 36-48 hour product of raw material storage, the content of 2-(4-methyl-3-cyclohexenyl group) isopropyl alcohol and methylnonanone also occurs defective, sees Table 6.
4, in storage 24 hours, maintain the temperature in the heap below 30 ℃, product is all qualified, constant product quality.
To sum up discuss, think that raw material is from plucking rear storage front 24 hours, when in three heaps, maintaining the temperature at below 30 ℃, the injection steady quality of producing, meet national requirements, so determine that this condition is that the Herba Houttuyniae storage condition is critical the best (storage temperature is less than 30 ℃, and storage time was less than 24 hours).
Simultaneously, compared with prior art, the present invention has adjusted the consumption of sodium chloride, the consumption of sodium chloride is changed to 0.45% (with respect to fresh Herba Houttuyniae), so that the original osmotic pressure of Herba Houttuyniae injectio and dilution are rear (clinically, the 250ml 5% glucose injection dilution of 100ml Herba Houttuyniae injectio) osmotic pressure is more suitable for clinical use all at 280～310m mOsm.
Test example three Herba Houttuyniae injectio etc. ooze the research of adjusting
By clinical method, namely the 100ml Herba Houttuyniae injectio has been investigated 12 batches of Herba Houttuyniae injectio osmotic pressuries after diluting with 250ml 5% glucose injection.Wherein, sample 1～6 is standby according to existing Herba Houttuyniae injectio metric system, and the consumption of sodium chloride is 0.35% of fresh Herba Houttuyniae; Sample 7～12 is according to the method preparation of embodiment 1～6.The osmotic pressure result who measures sees Table 7.
Osmotic pressure in table 7, the different Herba Houttuyniae injectio
The research of more than four kind of Tween 80 serious adverse reaction of test example---machin class hypersensitive test
Herba Houttuyniae injectio to 2 enterprises produce adopts respectively different manufacturers, variable concentrations Tween 80 to compare research as solubilizing agent.
1 animal and material
1.1 laboratory animal
Machin, body weight 4.5～6kg, male, animal credit number: SCXK (capital)-0005 is provided by the prosperous living resources institute of Beijing Xie Er.Laboratory environment: 15～25 ℃ of temperature, relative humidity 40～60%.
1.2 experimental drug and reagent
This tests used medicine: 1. contain the Herba Houttuyniae injectio that 0.125% (with respect to fresh Herba Houttuyniae) Guangzhou Chemical Reagent Factory is produced Tween 80, provided by Zhengqing Pharmaceutical Group Corp., Ltd., Hunan Prov., make the Herba Houttuyniae re-distilled liquid in strict accordance with standards of pharmacopoeia, add again 0.125% (with respect to fresh Herba Houttuyniae) Guangzhou chemistry Tween 80, be made into injection, 115 ℃ of sterilization 30min encapsulate for subsequent use; 2. contain the Herba Houttuyniae injectio that 0.125%, 0.15% (with respect to fresh Herba Houttuyniae) Nanjing WeiEr chemical engineering Co., Ltd produces Tween 80, Sanjiu Pharmaceutical Industry Co., Ltd., Ya'an City provides by Sichuan, make the Herba Houttuyniae re-distilled liquid in strict accordance with standards of pharmacopoeia, add respectively again 0.125% or 0.15% concentration Nanjing Weir Tween 80, be made into injection, encapsulation is for subsequent use after the sterilization.
Tween 80: Guangzhou Chemical Reagent Factory, product batch number 20081201-1; Nanjing WeiEr chemical engineering Co., Ltd, product batch number 090901.
0.9% sodium chloride injection: Beijing Double-Crane Pharmaceutical Co., Ltd, lot number C200906092.
Monkey IgE, histamine ELISA test kit (48T), U.S. Rapidbio Lab product, product batch number: monkey IgE 9B024s; Monkey histamine 9B011s.
1.3 key instrument
Infusion pump, SK-600I, Shenzhen medical device technology development corporation, Ltd. of dark section; The GL-20B High speed refrigerated centrifuge, Anting Scientific Instrument Factory, Shanghai; Full-automatic microplate reader: MULTISKAN MK3, Thermo, USA; Electro-heating standing-temperature cultivator: DH4000A, Tianjin Tai Site; MINI shaker:MH-1, kylin-Bell Lab Instruments QILINBEIER.
2 methods
2.1 grouping
With machin according to the body weight random packet, 3 every group, totally 4 groups.Be respectively:
A group: normal saline group;
B group: contain 0.125% Guangzhou chemistry Tween 80 Herba Houttuyniae injectio group;
C group: contain 0.125% Nanjing Weir Tween 80 Herba Houttuyniae injectio group;
D group: contain 0.15% Nanjing Weir Tween 80 Herba Houttuyniae injectio group.
2.2 test method
Test behavior, hair color, the mental status and defecation thereof, the diet of observing machin in front 3 days, whether take the photograph the regimen condition normal.The situation such as eyelid, mouth, neck, abdominal part, extremity skin of monkey is respectively organized in observation before on-test, and behavior, gait, the body coordination ability, the mental status etc.Once daily after animal is fixing, volume is 40.0ml/kg, forelimb vein constant infusion (speed is 5ml/min, the sterile working).Before the administration and observe the reaction symptom of every monkey after the administration in the 24h, record symptom time of occurrence, extinction time, and be judged to be the typical case, be not true to type and asymptomatic according to the weight of symptom.10min gets blood examination survey histamine, IgE level after reaching drug withdrawal before the administration.If animal dead occurs, then to dissect immediately, each main organs of perusal has Non Apparent Abnormality, and the heart, liver, spleen, lung, kidney, thymus are carried out pathological examination.
2.3 monkey anaphylactoid reaction criterion
2.3.1 symptom grade scale
The partial symptoms of class hypersensitive test and test operation, the factor such as fixing cause that animal is terrified, indignation, struggle, occur when escaping follow performance comparatively similar, both are easy to obscure and cause erroneous judgement.So with the performance of machin after the administration be divided into classical symptom, the symptom that is not true to type and asymptomatic 3 grades.
Table 11 monkey symptom grade scale
2.3.2 monkey anaphylactoid reaction criterion
Judging whether tested medicine can bring out machin when anaphylactoid reaction occurring, needs in conjunction with animal symptom and two indexs of Plasma Histamine value rising degree, carry out synthetic determination.
Table 12 monkey anaphylactoid reaction criterion
2.4 the date processing data are all used
Expression, relatively employing One-Way ANOVA (one factor analysis of variance) method between each group, homogeneity of variance is checked with Student-Newman-Keuls, heterogeneity of variance Tamhane ' sT2 check.P＜0.05 is for there being statistical significance.
3 results
3.1 symptom analysis
The classical symptom of anaphylactoid reaction does not all appear in 4 groups of machins after administration, the result shows: 2 enterprise's productions, use respectively the Herba Houttuyniae injectio of 2 kinds of domestic Tween 80 preparations of 0.125%, 0.15% (with respect to fresh Herba Houttuyniae) concentration, the classical symptom that anaphylactoid reaction appears in machin is not all brought out in intravenous drip.B group, C group respectively have 1 monkey to occur in the administration process with fixed mount scratch face, and skin of face shows slightly the reaction of flushing; The symptoms that are not true to type such as the skin of face flushing gently swells, ear's red heat appear during 1 monkey administration of D group.But these symptoms are few and light, can not be judged to be the classical symptom of anaphylactoid reaction.
3.2 blood plasma IgE
Each is organized, and IgE content all is lower than ELISA test kit detection minimum 0ug/ml in the forward and backward blood plasma of machin administration, finds regular the variation.
3.3 Plasma Histamine
Each treated animal, only B group (namely containing 0.125% Guangzhou chemistry Tween 80 Herba Houttuyniae injectio group) Plasma Histamine raises 64.27%, but does not surpass more than 1 times.Other each treated animal Plasma Histamines all surpass 50% without obviously raising.The histamine value is increased to the 1.49ng/ml behind monkey medicine of B group, and the forward and backward Plasma Histamine value of all the other each machin administrations all is lower than 1ng/ml.
Table 13 respectively organize machin administration Plasma Before And After histamine content situation of change (
N=3)
3.4 machin anaphylactoid reaction result of determination
Comprehensive symptom and the Plasma Histamine value situation of change of respectively organizing after the machin administration, the result shows: 2 enterprise's productions, 2 kinds of domestic Tween 80s that use respectively 0.125% or 0.15% concentration (with respect to fresh Herba Houttuyniae) are respectively organized Herba Houttuyniae injectio as solubilizing agent, after the intravenous drip, typical anaphylactoid reaction does not all appear.
The sterilising conditions screening test of test example five Herba Houttuyniae injectio
According to the aseptic assurance requirement of injection, adopt the SAL (Salmonella)＜10 of terminally sterilised sterile product
-6, i.e. F0 〉=8.So in the constant situation of preparation technique for houttuynia cordata injection, respectively following 3 kinds of sterilising conditions are compared investigation: 1. 115 ℃, 32 minutes (F0 〉=8) (embodiment 1); 2. 121 ℃, 8 minutes (F0 〉=8) (embodiment 3); 3. 121 ℃, 12 minutes (F0 〉=12) (embodiment 4).Investigating index mainly is the situation of change of medicinal liquid assay before and after the sterilization, PH, visible foreign matters (with the rate of qualifiid of the lamp inspection evaluation), haemolysis, the results are shown in Table 14:
Herba Houttuyniae injectio sampling test result under 3 sample sterilising conditions of table 14
Show by table 14 data: 3 kinds of sterilising conditions are little on the content before and after the Herba Houttuyniae injectio sterilization, PH impact.Haemolysis and the agglutination test of finished product is all qualified after the sterilization, but the rate of qualifiid of the lamp inspection of finished product differs greatly, and wherein the yield of finished product was the highest afterwards with sterilization in 115 ℃, 32 minutes.In order further to investigate each sterilising conditions to the impact of finished product stability, 3 batch samples have been carried out respectively 3 months acceleration and ambient stable investigation, following table 15 as a result:
Herba Houttuyniae injectio sample stability under 3 kinds of sterilising conditions of table 15 is investigated the result
Data by table 15 show: the Herba Houttuyniae injectio sample quality that adopts 3 kinds of sterilising conditions to prepare is all stable.So the test data of associative list 1 has been selected the wherein the highest sterilising conditions of finished product lamp inspection yield: 115 ℃, 32 minutes, as the final sterilization condition of Herba Houttuyniae injectio.
The specific embodiment
The present invention is further elaborated below in conjunction with the specific embodiment, the present invention do not limited.
Embodiment 1
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 2000ml, carry out again redistillation, collect re-distilled liquid 1000ml, add 2.5g polyoxyethylene sorbitan monoleate and 7g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 32 minutes, and be get final product for 115 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 24 hours, and reserve temperature can not be above 28 ℃.Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Embodiment 2
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 1000ml, carry out again redistillation, collect re-distilled liquid 800ml, add 2.5g polyoxyethylene sorbitan monoleate and 7g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 8 minutes, and be get final product for 110 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 24 hours, and reserve temperature can not be above 28 ℃.Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Embodiment 3
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 1000ml, carry out again redistillation, collect re-distilled liquid 800ml, add 1.0g polyoxyethylene sorbitan monoleate and 8g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 8 minutes, and be get final product for 121 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 20 hours, and reserve temperature can not be above 28 ℃.Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Embodiment 4
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 2000ml, carry out again redistillation, collect re-distilled liquid 1000ml, add 2.5g polyoxyethylene sorbitan monoleate and 7g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 12 minutes, and be get final product for 121 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 28 hours, and reserve temperature can not be above 28 ℃.
Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Embodiment 5
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 3000ml, carry out again redistillation, collect re-distilled liquid 1000ml, add 4.0g polyoxyethylene sorbitan monoleate and 8g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 40 minutes, and be get final product for 121 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 20 hours, and reserve temperature can not be above 28 ℃.
Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Embodiment 6
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 2000ml, carry out again redistillation, collect re-distilled liquid 1000ml, add 2.4g polyoxyethylene sorbitan monoleate and 6.5g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 20 minutes, and be get final product for 114 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 24 hours, and reserve temperature can not be above 28 ℃.
Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Embodiment 7
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 2500ml, carry out again redistillation, collect re-distilled liquid 1000ml, add 2.5g polyoxyethylene sorbitan monoleate and 7.5g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 32 minutes, and be get final product for 115 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 24 hours, and reserve temperature can not be above 28 ℃.
Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Embodiment 8
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 2000ml, carry out again redistillation, collect re-distilled liquid 1000ml, add 2.5g polyoxyethylene sorbitan monoleate and 6g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 36 minutes, and be get final product for 118 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 24 hours, and reserve temperature can not be above 28 ℃.
Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Embodiment 9
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 2000ml, carry out again redistillation, collect re-distilled liquid 800ml, add 2.5g polyoxyethylene sorbitan monoleate and 7g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 25 minutes, and be get final product for 117 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 23 hours, and reserve temperature can not be above 28 ℃.
Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Embodiment 10
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 2000ml, carry out again redistillation, collect re-distilled liquid 1000ml, add 2.8g polyoxyethylene sorbitan monoleate and 7.5g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 32 minutes, and be get final product for 116 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 24 hours, and reserve temperature can not be above 28 ℃.
Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Embodiment 11
Get bright Herba Houttuyniae 2000g and carry out steam distillation, collect just distillate 2000ml, carry out again redistillation, collect re-distilled liquid 1000ml, add 3g polyoxyethylene sorbitan monoleate and 9g sodium chloride, mixing injects water and makes into 1000ml, filters, embedding was sterilized 32 minutes, and be get final product for 115 ℃.
Wherein, bright Herba Houttuyniae is GAP base raw material, and storage time can not surpass 24 hours, and reserve temperature can not be above 28 ℃.
Gained Herba Houttuyniae injectio steady quality, heat source response, active constituent content meet the quality standard requirement.
Claims (22)
1. a Herba Houttuyniae injectio adopts following method to be prepared from: to get a certain amount of fresh Herba Houttuyniae, adopt steam distillation to prepare distillate; Add adjuvant, injection is made in sterilization; Wherein, the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 28 hours.
2. injection claimed in claim 1 is characterized in that adopting twice steam distillation to prepare distillate, with fresh Herba Houttuyniae with vapor distillation after, with the distillate redistillation that obtains, obtain re-distilled liquid again.
3. injection claimed in claim 2, it is characterized in that distillate that first distillation extraction obtains and the volume/mass of fresh Herba Houttuyniae are 1: 0.5～1.5 than (v/w), the re-distilled liquid that redistillation extracts amasss with fresh fish raw meat cursive script/and mass ratio (v/w) is 1: 1.5～2.5.
4. injection claimed in claim 1, it is characterized in that the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 26 hours.
5. injection claimed in claim 1, it is characterized in that the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 24 hours.
6. injection claimed in claim 1 is characterized in that adjuvant is polyoxyethylene sorbitan monoleate and sodium chloride, and wherein, the consumption of polyoxyethylene sorbitan monoleate is 0.05%～0.2% of fresh Herba Houttuyniae, and the consumption of sodium chloride is 0.3%～0.45% of fresh Herba Houttuyniae.
7. injection claimed in claim 6, the consumption that it is characterized in that polyoxyethylene sorbitan monoleate is 0.125% of fresh Herba Houttuyniae, the consumption of sodium chloride is 0.35% of fresh Herba Houttuyniae.
8. injection claimed in claim 1 is characterized in that sterilising conditions is:
Sterilized 8～40 minutes.
9. injection claimed in claim 8 is characterized in that sterilising conditions is: sterilized 32 minutes for 115 ℃.
10. claim 6 or 7 described injection is characterized in that polyoxyethylene sorbitan monoleate satisfies following requirement:
Color is colourless to faint yellow, acid number≤2.0, and saponification number is 45～55, acid-base value is 5.0～7.5, moisture≤1.0%, residue on ignition≤0.15%, peroxide value≤10, arsenic salt≤0.0002%, myristic acid≤1.0%, Palmic acid≤2.0%, palmitoleic acid≤1.0%, stearic acid≤2.0%, oleic acid 〉=90.0%, linoleic acid≤3.0%, linolenic acid≤1.0%, oxirane≤0.0001%, dioxane≤0.001% contains endotoxic amount less than 0.6EU among every 1mg, haemolysis and coagulation: it is an amount of to get this product, accurately weighed, add solution that water makes 6mg/ml as test liquid, must not haemolysis.
11. injection claimed in claim 1 is characterized in that being equivalent in every 1ml injection Herba Houttuyniae crude drug amount 2g.
12. the preparation method of a Herba Houttuyniae injectio is comprised of following step: get a certain amount of fresh Herba Houttuyniae, adopt steam distillation to prepare distillate; Add adjuvant, injection is made in sterilization; Wherein, the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 28 hours.
13. the described method of claim 12 is characterized in that adopting twice steam distillation to prepare distillate, with fresh Herba Houttuyniae with vapor distillation after, with the distillate redistillation that obtains, obtain re-distilled liquid again.
14. the described method of claim 13, it is characterized in that distillate that first distillation extraction obtains and the volume/mass of fresh Herba Houttuyniae are 1: 0.5～1.5 than (v/w), the re-distilled liquid that redistillation extracts amasss with fresh fish raw meat cursive script/and mass ratio (v/w) is 1: 1.5～2.5.
15. the described method of claim 12, it is characterized in that the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 26 hours.
16. the described method of claim 15, it is characterized in that the fresh-keeping condition of described fresh Herba Houttuyniae is: the Herba Houttuyniae after gathering is stored under the temperature that is no more than 30 ℃, and the time is no more than 24 hours.
17. the described method of claim 12 is characterized in that adjuvant is polyoxyethylene sorbitan monoleate and sodium chloride, wherein, the consumption of polyoxyethylene sorbitan monoleate is 0.05%～0.2% of fresh Herba Houttuyniae, and the consumption of sodium chloride is 0.3%～0.45% of fresh Herba Houttuyniae.
18. the described method of claim 17, the consumption that it is characterized in that polyoxyethylene sorbitan monoleate is 0.125% of fresh Herba Houttuyniae, and the consumption of sodium chloride is 0.35% of fresh Herba Houttuyniae.
19. the described method of claim 12 is characterized in that sterilising conditions is: sterilized 8～40 minutes for 110 ℃～121 ℃.
20. the described method of claim 19 is characterized in that sterilising conditions is: sterilized 32 minutes for 115 ℃.
21. claim 17 or 18 described methods is characterized in that polyoxyethylene sorbitan monoleate satisfies following requirement:
Color is colourless to faint yellow, acid number≤2.0, and saponification number is 45～55, acid-base value is 5.0～7.5, moisture≤1.0%, residue on ignition≤0.15%, peroxide value≤10, arsenic salt≤0.0002%, myristic acid≤1.0%, Palmic acid≤2.0%, palmitoleic acid≤1.0%, stearic acid≤2.0%, oleic acid 〉=90.0%, linoleic acid≤3.0%, linolenic acid≤1.0%, oxirane≤0.0001%, dioxane≤0.001% contains endotoxic amount less than 0.6EU among every 1mg, haemolysis and coagulation: it is an amount of to get this product, accurately weighed, add solution that water makes 6mg/ml as test liquid, must not haemolysis.
22. the described method of claim 12 is characterized in that being equivalent in its every 1ml injection Herba Houttuyniae crude drug amount 2g.
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Cited By (2)
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| CN105982992A (en) * | 2015-02-10 | 2016-10-05 | 李长太 | Anti-inflammatory and antasthmatic injection for enema-drip therapy |
| CN110721234A (en) * | 2019-11-29 | 2020-01-24 | 成都新亨药业有限公司 | Preparation method of houttuynia cordata injection for livestock |
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2011
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| CN105982992A (en) * | 2015-02-10 | 2016-10-05 | 李长太 | Anti-inflammatory and antasthmatic injection for enema-drip therapy |
| CN110721234A (en) * | 2019-11-29 | 2020-01-24 | 成都新亨药业有限公司 | Preparation method of houttuynia cordata injection for livestock |
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