CN101249170A - Preparation of houttuynia cordata freeze-dried powder needle for injections - Google Patents
Preparation of houttuynia cordata freeze-dried powder needle for injections Download PDFInfo
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- CN101249170A CN101249170A CNA2008100198568A CN200810019856A CN101249170A CN 101249170 A CN101249170 A CN 101249170A CN A2008100198568 A CNA2008100198568 A CN A2008100198568A CN 200810019856 A CN200810019856 A CN 200810019856A CN 101249170 A CN101249170 A CN 101249170A
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Abstract
The invention discloses a preparation method of a heartleaf houtluynia freeze-dried injection. The invention has the methods as follows: heartleaf houtluynia is obtained, washed away, dried, and crushed; and then the supercritical fluid extraction, the water vapour distillation, the membrane separation and the freeze-drying are performed, so that the heartleaf houtluynia freeze-dried injection is obtained. The heartleaf houtluynia freeze-dried injection is prepared through the combined technology of the supercritical fluid extraction, ultrafiltration and the freeze-drying, the ineffective impurities which cause adverse reaction are removed, the manufacturing technique is more advanced and reasonable, the product stability is increased, the pharmacological experiments prove that the curative effect of the product is increased remarkably, and the adverse reaction are greatly decreased.
Description
One. technical field:
The invention belongs to the pharmaceutical technology field of Chinese medicine, be specifically related to a kind of preparation method of houttuynia cordata freeze-dried powder needle for injections.
Two. background technology:
Herba Houttuyniae is the herb of Saururaceae Houttuynia plant Herba Houttuyniae Houttuynia cordata Thunb., its nature and flavor suffering, cold, effect such as have heat-clearing and toxic substances removing, detumescence and apocenosis, inducing diuresis for treating stranguria syndrome and end that expectorantization is coughed.Clinically be mainly used in that lung abscess vomiting pus, expectorant dyspnea of heat type are coughed, hematodiarrhoea pyretic stranguria, carbuncle sore tumefacting virus.The Herba Houttuyniae effective ingredient mainly contains decanoylacetaldehyde (houttuynine sodium bisulfite), methyl nonyl ketone, lauryl aldehyde.Herba Houttuyniae injectio has heat clearing away, detoxifcation, dampness removing effect.The clinical lung abscess that is used for the treatment of, phlegm-heat cough, evident in efficacy.
But Herba Houttuyniae injectio many untoward reaction occurred in clinical use.The data of national drug untoward reaction monitoring center statistics show, since 2000, and example, wherein example surplus the serious adverse reaction 200 surplus the untoward reaction relevant with Herba Houttuyniae class injection has 4000.Report shows, use the Herba Houttuyniae injectio injection after, cause serious adverse reactions such as patient's anaphylactic shock, systemic anaphylaxis, uncomfortable in chest, cardiopalmus, dyspnea and severe drug rash, show that clearly there is serious potential safety hazard in this medicine in clinical application.
State Food and Drug Administration notifies, and requires from June 1st, 2006, suspends 7 kinds of injections such as using Herba Houttuyniae injectio in China, suspends all kinds of applications for registration of accepting and examine 7 injections such as Herba Houttuyniae injectio.
Carry out analysis-by-synthesis by the untoward reaction that Herba Houttuyniae injectio is occurred, drip when we think except individual variation (especially allergic constitution), drug combination, intravenous injection the speed reason such as too fast, its basic reason is that former preparation technology is unreasonable: extracting, failing the anaphylaxis material is removed fully when filtering; In dosing technology, added the solubilizing agent soil temperature-80 that itself has haemolysis; Owing to be aqueous solution for injection, the stability of product is poor than freeze-dried powder.At present, although Herba Houttuyniae injectio also has many patents, these patents are not all thoroughly dealt with problems.As application number be 200410096731.7 patent " preparation technique for houttuynia cordata injection " though adopted the carbon dioxide supercritical fluid extraction technology, do not use ultrafiltration and Freeze Drying Technique, and still added soil temperature-80; Application number be 200410046098.0 patent " a kind of houttuynia cordata freeze-dried powder needle injection and preparation method thereof " though adopted Freeze Drying Technique and do not used soil temperature-80, do not adopt carbon dioxide supercritical fluid extraction and hyperfiltration technique.
Three. summary of the invention:
The object of the present invention is to provide few, the preparation method of houttuynia cordata freeze-dried powder needle for injections efficiently of a kind of untoward reaction.
The present invention is directed to above-mentioned existing problems and carried out corresponding major tuneup.Adopt supercritical extraction and ultrafiltration to remove the anaphylaxis material, solubilizing agent soil temperature-80 is used in cancellation, aqueous solution for injection is prepared into stay-in-grade injection freeze-dried powder injection, thereby has significantly improved the product curative effect, greatly reduces untoward reaction.
A kind of preparation method of houttuynia cordata freeze-dried powder needle for injections, it is characterized in that preparation process is as follows: (1) gets Herba Houttuyniae 2kg, and cleaning, drying are pulverized; (2) carry out carbon dioxide supercritical fluid extraction, with the extract steam distillation, distillate carries out hyperfiltration treatment; (3) filtrate adds proper auxiliary materials, lyophilization, promptly.
Condition at the carbon dioxide supercritical fluid extraction described in the above-mentioned steps (2) is: extracting pressure 20-30mPa, temperature 20-50 ℃, CO
2Flow 20-60kg/h.
Condition at the steam distillation described in the above-mentioned steps (2) is: add 3～15 times of water in above-mentioned supercritical extract, distilled 1～6 hour, collect 0.5～4 times of distillate;
Condition in the ultrafiltration described in the above-mentioned steps (2) is: getting the distillate of above-mentioned steps 3, add water for injection to 1000ml, is that 3000～50000 ultrafilter membrane carries out ultra-filtration and separation with molecular weight;
In the cryodesiccated condition described in the above-mentioned steps (3) be: the ultrafiltrate of getting step (2), under aseptic condition, divide and be filled in the cillin bottle, elder generation's pre-freeze is to-40～55 ℃, kept 2～4 hours, regulate vacuum to 0.01mPa, sublimation drying 12～48 hours is warming up to 10～30 ℃ again, dry 4～8 hours.
Adjuvant described in the above-mentioned steps (3) is a kind of in glucose, sodium chloride, mannitol or the lactose injection lyophilisation additives.
The present invention has carried out preparation technology's improvement at the defective that former technology exists, and adopts combined methods such as supercritical extraction, ultrafiltration and lyophilization, removes the invalid impurity that causes untoward reaction, has improved the stability of product.Prove by pharmacological evaluation, the curative effect of product is significantly improved, caused rat experiment heat pyrexia has significant refrigeration function to houttuynia cordata freeze-dried powder needle to typhoid fever one paratyphoid vaccine, incidence rate of adverse reaction is reduction greatly also, and experimental result shows that the Herba Houttuyniae powder pin can not bring out irritated the sending out of a speed property and answer.
Four. the specific embodiment:
The preparation method of embodiment 1-houttuynia cordata freeze-dried powder needle for injections
Get Herba Houttuyniae 2000g, cleaning, drying are pulverized, and cross 20 mesh sieves, carry out carbon dioxide supercritical fluid extraction, extracting pressure 25mpa, 40 ℃ of temperature, CO
2Flow 50kg/h gets supercritical extract, adds 5 times of water gagings, vapor distillation 3 hours is collected distillate, adds the 50g glucose, and add the injection water to 1000ml, and be that 3000 ultrafilter membrane carries out ultrafiltration with molecular weight, branch is filled in the cillin bottle, elder generation's pre-freeze is to-45 ℃, kept 2 hours, and regulated vacuum to 0.1mbar, sublimation drying 24 hours, be warming up to 20 ℃ again, dry 6 hours.Quality inspection, packing, promptly.
The preparation method of embodiment 2-houttuynia cordata freeze-dried powder needle for injections
Get Herba Houttuyniae 2000g, cleaning, drying are pulverized, and cross 40 mesh sieves, carry out carbon dioxide supercritical fluid extraction, extracting pressure 25mPa, 40 ℃ of temperature, CO
2Flow 50kg/h gets supercritical extract, adds 5 times of water gagings, vapor distillation 3 hours is collected distillate, adds the 30g lactose, and add the injection water to 1000ml, and be that 5000 ultrafilter membrane carries out ultrafiltration with molecular weight, branch is filled in the cillin bottle, elder generation's pre-freeze is to-45 ℃, kept 2 hours, and regulated vacuum to 0.1mbar, sublimation drying 24 hours, be warming up to 20 ℃ again, dry 8 hours.Quality inspection, packing, promptly.
Embodiment 3 the pharmacodynamic experiments---internally influence of toxicity heating
Respectively houttuynia cordata freeze-dried powder needle (new technology) and Herba Houttuyniae injectio (former technology) are mixed with 1mg/mL with 0.9% sodium chloride injection.Get SPF level SD rat, body weight 150-170g male and female half and half are surveyed normal anus temperature 2-3 time earlier, survey 1 time every 30 minutes, and double mensuration body temperature differs should be greater than 0.2 degree, and averaging is normal body temperature.Body temperature is more or less the same in 1.0 ℃ between the individuality.Every rat skin lower injection Typhoid-Paratyphoid vaccine 1ml/kg measured an anus temperature every 1 hour, when treating that fervescence is more than 0.6 ℃ (about l-4 hour), divided equally 5 groups at random, 10 every group, began administration.Be high, medium and low three the dosage groups of normal saline group, houttuynia cordata freeze-dried powder needle (new technology) (2.0mL, 1.0ml, 0.5mL), Herba Houttuyniae injectio (former technology) group.30,60,120 minutes take temperatures are once observed the body temperature situation of change after the administration, the results are shown in Table 1.
Table 1. Herba Houttuyniae lyophilized powder (new technology) is to the influence of experimental heating rat temperature
Compare with normal saline: *: p＜0.05; *: p＜0.01; * *: p＜0.001
Compare with Herba Houttuyniae injectio: #:p＜0.05; The F check
Last table explanation, caused rat experiment heat pyrexia has significant refrigeration function to houttuynia cordata freeze-dried powder needle (new technology) to the Typhoid-Paratyphoid vaccine.Compare Deng dosage and Herba Houttuyniae injectio, the effect of houttuynia cordata freeze-dried powder needle preparation is stronger.
Embodiment 4-passive cutaneous anaphylaxis test
1, medicine and reagent
The Herba Houttuyniae powder injection is by the Chinese medicine academy of Nanjing University of Traditional Chinese Medicine preparation, lot number: 071209; Trichosanthin, Shanghai family planning institute is given; According to train of thought orchid, Shanghai chemical reagent purchasing and supply station packing, lot number: 050518.
2, animal SD rat is male, and body weight 200 ± 20g is provided by Nanjing University of Traditional Chinese Medicine's Experimental Animal Center, the quality certification number: SYXK (Soviet Union) 2002-0053.
3, experimental technique
(1), sensitization test (STT)
Get 200 ± 20g male rat.After 1 of bacillus calmette-guerin vaccine (adjuvant) added the normal saline dilution of 2 times of amounts, add Radix Trichosanthis and fully be mixed into 2.5mg/mL, every Mus injection 0.4mL injects 0.1mL respectively in the rat paw position, and the remainder multi-point injection is in muscle and subcutaneous.Herba Houttuyniae powder injection group is mixed with corresponding injection with the powder pin earlier on request, after then bacillus calmette-guerin vaccine being diluted with the doubling dose medicinal liquid, and every Mus injection 0.4mL, method is with the Radix Trichosanthis group.With Herba Houttuyniae powder injection and 4 rats of Radix Trichosanthis difference sensitization.Inject and got blood through carotid artery in back 10 days, the centrifugalize antiserum, put below-4 ℃ preserve standby.
(2), passive sensitization of skin test
Other gets 200 ± 20g normal rat, the back unhairing, respectively at the antiserum 0.1mL/ point of subcutaneous injection by Herba Houttuyniae powder injection and Radix Trichosanthis solution sensitization, azovan blue (azovan blue content is 1%) the solution 1mL/200g that the difference intravenous injection is prepared Radix Trichosanthis solution (2mg/mL) 1mL/200g and prepared with the Herba Houttuyniae powder injection with 1% azovan blue behind the 48h.Put to death animal behind the 30min, the upset skin of back is measured and the blue reaction of record spot diameter size, and the locus coeruleus diameter is judged to be the positive the above person of 5mm.
4, experimental result
The locus coeruleus area is as shown in table 2:
Table 2. Herba Houttuyniae powder injection is to the influence of rat passive anaphylaxis skin locus coeruleus area
By table 2 as seen, the diameter of the locus coeruleus that the Herba Houttuyniae powder injection brings out should belong to and can not bring out the medicine scope that speed is sent out paraphilia all less than 5mm.The locus coeruleus diameter of positive compound Radix Trichosanthis is all greater than 20mm.
5, conclusion: should belong to by the visible Herba Houttuyniae powder injection of this experimental result and can not bring out speed and send out the anaphylactoid medicine of property.
Claims (6)
1, a kind of preparation method of houttuynia cordata freeze-dried powder needle for injections, it is characterized in that preparation process is as follows: (1) gets Herba Houttuyniae 2kg, and cleaning, drying are pulverized; (2) carry out carbon dioxide supercritical fluid extraction, with the extract steam distillation, distillate carries out hyperfiltration treatment; (3) filtrate adds proper auxiliary materials, lyophilization, promptly.
2, preparation method according to claim 1 is characterized in that in the condition of the carbon dioxide supercritical fluid extraction described in the step (2) being: extracting pressure 20-30m Pa, temperature 20-50 ℃, CO
2Flow 20-60kg/h.
3, preparation method according to claim 1 is characterized in that in the condition of the steam distillation described in the step (2) being: add 3～15 times of water in above-mentioned supercritical extract, distilled 1～6 hour, collect 0.5～4 times of distillate.
4, preparation method according to claim 1 is characterized in that in the condition of the ultrafiltration described in the step (2) being: getting the distillate of above-mentioned steps 3, add water for injection to 1000ml, is that 3000～50000 ultrafilter membrane carries out ultra-filtration and separation with molecular weight.
5, preparation method according to claim 1, it is characterized in that being: the ultrafiltrate of getting step 4 in the cryodesiccated condition described in the step (3), under aseptic condition, divide and be filled in the cillin bottle, elder generation's pre-freeze is to-40～55 ℃, kept 2～4 hours, and regulated vacuum to 0.01-0.1mbar, sublimation drying 12～48 hours, be warming up to 10～30 ℃ again, dry 4～8 hours.
6, preparation method according to claim 1 is characterized in that the adjuvant described in the step (3) is a kind of in glucose, sodium chloride, mannitol or the lactose injection lyophilisation additives.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2008100198568A CN101249170B (en) | 2008-03-19 | 2008-03-19 | Preparation of houttuynia cordata freeze-dried powder needle for injections |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100198568A CN101249170B (en) | 2008-03-19 | 2008-03-19 | Preparation of houttuynia cordata freeze-dried powder needle for injections |
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| CN101249170A true CN101249170A (en) | 2008-08-27 |
| CN101249170B CN101249170B (en) | 2010-12-15 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104062412A (en) * | 2014-06-30 | 2014-09-24 | 南京中医药大学 | Comprehensive evaluation method for passive cutaneous anaphylaxis test |
| CN114601807A (en) * | 2022-03-18 | 2022-06-10 | 黑龙江省中医药科学院 | Fritillary lung clearing concentrated pill and preparation method and application thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1515250A (en) * | 2003-08-25 | 2004-07-28 | 刘立刚 | New houttuynin sodium injection preparation and its preparation method |
| CN1559522A (en) * | 2004-02-24 | 2005-01-05 | 姚仲青 | Houttuynia injection and its processing technology |
| CN1634495A (en) * | 2004-12-03 | 2005-07-06 | 江西省中医药研究院 | Preparation technique for houttuynia cordata injection |
-
2008
- 2008-03-19 CN CN2008100198568A patent/CN101249170B/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104062412A (en) * | 2014-06-30 | 2014-09-24 | 南京中医药大学 | Comprehensive evaluation method for passive cutaneous anaphylaxis test |
| CN114601807A (en) * | 2022-03-18 | 2022-06-10 | 黑龙江省中医药科学院 | Fritillary lung clearing concentrated pill and preparation method and application thereof |
| CN114601807B (en) * | 2022-03-18 | 2023-02-24 | 黑龙江省中医药科学院 | Preparation method of fritillaria lung-clearing concentrated pills |
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| CN101249170B (en) | 2010-12-15 |
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Granted publication date: 20101215 Termination date: 20200319 |