CN1751691A - Small volume intravenous injection of gastrodine and its prepn. method - Google Patents
Small volume intravenous injection of gastrodine and its prepn. method Download PDFInfo
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- CN1751691A CN1751691A CN 200510067866 CN200510067866A CN1751691A CN 1751691 A CN1751691 A CN 1751691A CN 200510067866 CN200510067866 CN 200510067866 CN 200510067866 A CN200510067866 A CN 200510067866A CN 1751691 A CN1751691 A CN 1751691A
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Abstract
A low-capacity intravenous injection of gastrodine for treating neurasthenia, neurasthenia syndrome, cerebral trauma syndrome, dizziness, Meniere's disease, reuralgia, headache, etc is prepared from gastrodine, the water for injection and metallic chelating agent. Its preparing process is also disclosed.
Description
[technical field]
The invention belongs to field of medicine preparations, be specifically related to gastrodine vein small-volume injection and preparation method thereof.
[background technology]
Gastrodine is the effective constituent that mainly contains in the perennial parasitic plant Rhizoma Gastrodiae of the orchid family (Gastrodia elata BL.).Gastrodine (Gastrodin), chemistry by name methylol benzene-β-D-Fructus Vitis viniferae is adjoined, fed glucoside (P-hydroxymethylPhenyl-β-D-glucopyranoside), white, needle-shaped crystals, 154 ℃-156 ℃ of fusing points, i.e. gastrodin.
Pharmacological evaluation shows that gastrodine can recover the dysequilibrium between cerebral cortex excitement and process of inhibition, has calmness, sleeps peacefully and central inhibitory action such as analgesia.Show by acute toxicity testing and sub-acute toxicity test: gastrodine does not all have influence to hemopoietic system, liver, renal function and blood fat.
At present, be that main active is applied to clinical having with the gastrodine: gastrodini, gastrodine capsule, gastrodine injection, gastrodia-tuer powder injection and gastrodine drop pill etc.
Application number is 02134016, denomination of invention is a gastrodia-tuer powder injection, mixture by gastrodine and water for injection dissolubility pharmaceutic adjuvant or water or water for injection dissolubility pharmaceutic adjuvant and water is formed, wherein, when the mixture of gastrodine and water for injection dissolubility pharmaceutic adjuvant or water for injection dissolubility pharmaceutic adjuvant and water makes up, the percentage by weight of gastrodine is 30～99.9%, and the weight percent content of the mixture of its water for injection dissolubility pharmaceutic adjuvant or water for injection dissolubility pharmaceutic adjuvant and water is 0.1～70%; When gastrodine and water combination, the percentage by weight of gastrodine is 85～99.9%, the weight percent content of its moisture is 0.1～15%, this injectable powder is an active component with the gastrodine, has calmness, sleeps peacefully, analgesia, vertigo, convulsion, epilepsy, improves cardio and vascular function, promotes myocardial cell energy metabolism and anti-ageing effect of waiting for a long time.
When gastrodine used as injection clinically, existing route of administration was intramuscular injection.Play a role behind blood through skin absorbs after the intramuscular injection, onset is slow; And the problem that intramuscular injection exists is that untoward reaction such as local redness, congestion, lump even muscular death may appear in patient infusion position pain and long term injections; Raw materials used in the production because there is the not high problem of purity in preparation technology's problem, also there is certain potential safety hazard.
Therefore, the vein small-volume injection that exploitation is relevant becomes focus, a kind of gastrodine vein small-volume injection is disclosed as Chinese patent (application number 200410016799.X), a kind of gastrodine injection that is directly used in venoclysis, containing gastrodine is active component and isoosmotic adjusting agent, cosolvent, antioxidant, stabilizing agent, complexing of metal ion agent and water for injection; Wherein every 1000ml contains 20mg～5000mg gastrodine, and injection is made through the 0.45um filtering with microporous membrane.The content of corresponding auxiliary material is not disclosed in the above-mentioned patent specification, also unexposed in an embodiment concrete preparation method.The inventor is through a large amount of test, and the gastrodine that utilizes purification more obtains having bioavailability height, good stability in conjunction with rational adjuvant amount, the clarity height, clinical easy to use, untoward reaction is little, curative effect vein small-volume injection rapidly.
[summary of the invention]
Technical problem to be solved by this invention provides a kind of bioavailability height, good stability, the clarity height, clinical easy to use, untoward reaction is little, curative effect gastrodine vein small-volume injection rapidly.
Another technical problem to be solved of the present invention provides a kind of injection that adopts the ultra-filtration technology that injection is handled, and contains the metal chelating agent of reasonable amount simultaneously, can effectively protect gastrodine.
Another technical problem to be solved of the present invention provides the preparation method of above-mentioned gastrodine vein small-volume injection.
The present invention is easily oxidized under the condition that metal ion exists in order to prevent gastrodine; add the complexing of metal ion agent and play the effect of protection active ingredient gastrodine; and adopt the ultra-filtration technology that injection is handled; its macromole invalid components is removed fully; the product biological availability height of gained, clinical easy to use, untoward reaction is little, curative effect is rapid; improve about 10%, can give full play to the pharmacological action of gastrodine.
Gastrodine vein small-volume injection of the present invention comprises gastrodine, water for injection, wherein contains the metal chelating agent of gross weight 0.01%～0.1%, and described gastrodine injection forms through the ultra-filtration technical finesse.
Gastrodine vein small-volume injection of the present invention contains the gastrodine of gross weight 1%～20%.
Described metal complex agent content is preferably 0.03%～0.05%.
Described metal chelating agent can be: Calcium Disodium Versenate or editic acid.
Described ultra-filtration is to adopt the ultrafiltration apparatus of intercepting molecular weight below 100,000 to carry out classified filtering 1～3 time.Described classified filtering is exactly to adopt the filter multiple times of filtration of holding back different molecular weight, to reach the purpose of progressively removing invalid components.Such as, first ultrafiltration gets the gastrodine solution of molecular weight below 100,000, the ultrafilter ultrafiltration of reuse molecular cut off below 5000, final bioavailability height, the gastrodine solution that clarity is high of getting.
The preparation method of a kind of gastrodine vein small-volume injection of the present invention, comprise the steps: gastrodine is handled through water precipitating, cold preservation, hyperfiltration technique, obtain the gastrodine ultrafiltrate, after adjust pH, sterilization, fill, packing are made gastrodine vein small-volume injection.
The preparation method of gastrodine vein small-volume injection of the present invention specifically comprises the steps:
Earlier with gastrodine and an amount of 80～90 ℃ of water for injection mixed dissolutions, after being placed to room temperature, 0～10 ℃ of cold preservation 12～48 hours, through 1～3 progressively filtration, ultrafiltration, the metal chelating agent of adding 0.01%～0.1%, last adjust pH is 5.0～7.0, and forms the gastrodine injection through sterilization, fill, packing.
Filtration of the present invention can be filtered through 1～3 time, be preferably 1～2 time, can adopt paper pulp to carry out pretreatment filters, first then ultrafiltration gets the gastrodine solution of molecular weight below 100,000, ultrafiltration gets the gastrodine solution of molecular weight below 5000 again, preferably adopts the ultrafilter of holding back 3000 following molecular weight.
Furtherly, the preparation method of gastrodine vein small-volume injection of the present invention comprises the steps:
A) earlier with gastrodine and an amount of 80～90 ℃ of water for injection mixed dissolutions, be placed to room temperature, 0～10 ℃ of cold preservation 12～48 hours is after the ultrafilter ultrafiltration of molecular cut off below 100,000, the ultrafilter ultrafiltration of reuse molecular cut off below 5000 gets the gastrodine ultrafiltrate;
B) in ultrafiltrate, add 0.01%～0.1% metal chelating agent, regulate pH5.0～7.0, sterilization, fill, pack the gastrodine injection.
The pH of gastrodine vein small-volume injection of the present invention is 5.0～7.0, is preferably pH5.8～6.2, and the pH value regulator can be selected this area regulator commonly used for use, such as 10% sodium hydroxide or 10% hydrochloric acid solution.
Sterilizing installation and technology that described sterilization can adopt those skilled in the art to use always.For example, use water-bath sterilization or steam sterilization, sterilized 30～45 minutes down at 100～110 ℃.
Preferably, the preparation method of gastrodine vein small-volume injection of the present invention comprises the steps:
A) earlier with gastrodine and an amount of 80～90 ℃ of water for injection mixed dissolutions, be placed to room temperature, 0～10 ℃ of cold preservation 24～32 hours is after the ultrafilter ultrafiltration of molecular cut off below 100,000, the ultrafilter ultrafiltration of reuse molecular cut off below 5000 gets the gastrodine ultrafiltrate;
B) in ultrafiltrate, add 0.03%～0.05% metal chelating agent, regulate pH5.8～6.2, sterilization, fill, pack the gastrodine injection.
The gastrodine vein small-volume injection that adopts preparation method of the present invention and get, character is a colourless clear liquid, specification can be 1ml:50mg, 2ml:200mg, 5ml:500mg, 10ml:2g, and most preferred specification is 2ml:200mg, 5ml:500mg.
Not only can intramuscular injection during gastrodine vein small-volume injection clinical practice of the present invention, be preferably intravenous drip, pain when intravenous drip can be avoided intramuscular injection and the long-term issuable untoward reaction of intramuscular injection.Intramuscular injection, each 200mg, 1～2 time on the one.Intravenous drip, each 500～1000mg once-a-day, uses with 250～500ml, 5% glucose injection or 0.9% sodium chloride injection dilution back.But small-volume injection long term administration of the present invention.
Gastrodine can recover the dysequilibrium between cerebral cortex excitement and process of inhibition, has calmness, sleeps peacefully and central inhibitory action such as analgesia.Gastrodine injection of the present invention is used for that preparation treatment god declines, god declines syndrome and the brain traumatic syndrome; Vertigo: Meniere, medicinal vertigo, traumatic vertigo, sudden deafness, vestibular neuronitis, vertebro-basilar artery insufficiency etc.; Neuralgia: trigeminal neuralgia, sciatica, occipital bone neuralgia etc.; Headache: the application of vascular headache, migraine, neurasthenia and the refreshing syndrome disease medicament that declines.
Added metal chelating agent in the small-volume injection of the present invention, gastrodine by easily oxidized, adds the effect that protection active ingredient gastrodine is played in the complexing of metal ion agent under the condition that metal ion exists.And research worker of the present invention is through a large amount of experimentation and analysis, think highly purified gastrodine, the product quality of gastrodine small-volume injection is effectively improved, can reach higher level aspect the safety indexes such as pyrogen, acute toxicity test, especially after using the intercepting molecular weight less than 5000 ultrafilter ultrafiltration, its macromole invalid components is removed fully, the product biological availability height of gained, clinical easy to use, untoward reaction is little, curative effect is rapid, improve about 10%, can give full play to the pharmacological action of gastrodine.Can adopt independent complexing of metal ion agent in the vein small-volume injection simultaneously, and, not only provide cost savings, the more important thing is the safety that has improved medicine without other adjuvants.
Therefore research worker of the present invention is handled gastrodine through water precipitating, cold preservation, hyperfiltration technique, sterilization, guaranteed that invalid components is removed fully, reduced the related substance in the preparation, the better stability of preparation of making, the clarity height, improve about 5% than common process, and stable curative effect, gastrodine injection intravenous drip administration, the untoward reaction such as local redness, congestion, lump even muscular death that injection site pain and long term injections may be occurred are after the intravenous drip administration, can directly enter blood and onset, effect rapidly.
[specific embodiment]
Following embodiment further describes the present invention, but described embodiment only is used to illustrate the present invention rather than restriction the present invention.
Embodiment 1
A) get 80 ℃ fresh water for injection 300ml, add gastrodine 100g, fully stir and make dissolving fully, be placed to room temperature, 10 ℃ of cold preservation 12 hours, after the ultrafilter ultrafiltration of molecular cut off below 100,000, the ultrafilter ultrafiltration of reuse molecular cut off below 5000, get the gastrodine ultrafiltrate, the sampling detection level.
B) Calcium Disodium Versenate of adding gross weight 0.03% in ultrafiltrate is regulated pH5.3, adds the injection water and makes it into 1000ml, and intermediate products promptly get the vein small-volume injection that contains the 100mg gastrodine among every 1ml after the assay was approved.With medicinal liquid through the end-filtration fill in ampoule, can adorn 1ml, 2ml, 5ml etc. for every, use the water-bath sterilization, 108 ℃ of sterilizations 30 minutes down, lamp inspection, clarity is 98%, packing promptly gets gastrodine vein small-volume injection finished product.
Embodiment 2
A) get 90 ℃ fresh water for injection 500ml, add gastrodine 200g, fully stir and make dissolving fully, be placed to room temperature, 5 ℃ of cold preservation 24 hours, after the ultrafilter ultrafiltration of molecular cut off below 100,000, the ultrafilter ultrafiltration of reuse molecular cut off below 3000, get the gastrodine ultrafiltrate, the sampling detection level.
B) Calcium Disodium Versenate of adding gross weight 0.04% in ultrafiltrate is regulated pH5.9, adds the injection water and makes it into 1000ml, and intermediate products promptly get the vein small-volume injection that contains the 200mg gastrodine among every 1ml after the assay was approved.With medicinal liquid through the end-filtration fill in ampoule, can adorn 1ml, 2ml, 5ml etc. for every, use steam sterilization, 110 ℃ of sterilizations 35 minutes down, lamp inspection, clarity is 99%, packing promptly gets gastrodine vein small-volume injection finished product.
Embodiment 3
A) get 85 ℃ fresh water for injection 100ml, add gastrodine 10g, fully stir and make dissolving fully, be placed to room temperature, 0 ℃ of cold preservation 48 hours, after the ultrafilter ultrafiltration of molecular cut off below 100,000, the ultrafilter ultrafiltration of reuse molecular cut off below 5000, get the gastrodine ultrafiltrate, the sampling detection level.
B) editic acid of adding 0.05% in ultrafiltrate is regulated pH7.0, adds the injection water and makes it into 1000ml, and intermediate products promptly get the vein small-volume injection that contains the 10mg gastrodine among every 1ml after the assay was approved.With medicinal liquid through the end-filtration fill in ampoule, can adorn 1ml, 2ml, 5ml etc. for every, 108 ℃ of following water-baths sterilizations 30 minutes, lamp inspection, clarity is 98%, packing promptly gets gastrodine vein small-volume injection finished product.
Embodiment 4
A) get 90 ℃ fresh water for injection 150ml, add gastrodine 50g, fully stir and make dissolving fully, be placed to room temperature, 4 ℃ of cold preservation 36 hours, after the ultrafilter ultrafiltration of molecular cut off below 100,000, the ultrafilter ultrafiltration of reuse molecular cut off below 3000, get the gastrodine ultrafiltrate, the sampling detection level.
B) Calcium Disodium Versenate of adding 0.03% in ultrafiltrate is regulated pH6.0, adds the injection water and makes it into 1000ml, and intermediate products promptly get the vein small-volume injection that contains the 50mg gastrodine among every 1ml after the assay was approved.With medicinal liquid through the end-filtration fill in ampoule, can adorn 1ml, 2ml, 5ml etc. for every, 108 ℃ of following steam sterilizations 40 minutes, lamp inspection, clarity is 98.5%, packing promptly gets gastrodine vein small-volume injection finished product.
Embodiment 5
A) get 90 ℃ fresh water for injection 250ml, add gastrodine 150g, fully stir and make dissolving fully, be placed to room temperature, 6 ℃ of cold preservation 36 hours, after the ultrafilter ultrafiltration of molecular cut off below 100,000, the ultrafilter ultrafiltration of reuse molecular cut off below 3000, get the gastrodine ultrafiltrate, the sampling detection level.
B) Calcium Disodium Versenate of adding 0.03% in ultrafiltrate is regulated pH6.0, adds the injection water and makes it into 1000ml, and intermediate products promptly get the vein small-volume injection that contains the 150mg gastrodine among every 1ml after the assay was approved.With medicinal liquid through the end-filtration fill in ampoule, can adorn 1ml, 2ml, 5ml etc. for every, 108 ℃ of following steam sterilizations 40 minutes, lamp inspection, clarity is 98.5%, packing promptly gets gastrodine vein small-volume injection finished product.
Experimental example 1
This experimental example be the embodiment of the invention 1 described 2ml:200mg with the outward appearance of 5ml:500mg vein small-volume injection, pH value, injection item under the detection of relevant every gainer.
Character: medicine composition injection of the present invention is a colourless clear liquid.
PH value: two appendix VIH measure according to Chinese Pharmacopoeia version in 2000, and medicine composition injection pH value of the present invention is 5.0-7.0, meets quality standard.
Pyrogen: get this product, inspection in accordance with the law (two appendix XID of Chinese Pharmacopoeia version in 2000 measure) dosage is slowly injected 1ml by the every kg of rabbit body weight, and is up to specification.
The undue toxicity: get this product, be diluted to the solution that every ml contains this product 100mg with sterile water for injection, check (two appendix XIC of Chinese Pharmacopoeia version in 2000 measure) in accordance with the law, this product is up to specification.
Aseptic: get this product, check (two appendix XIH of Chinese Pharmacopoeia version in 2000 measure) in accordance with the law, this product is up to specification.
Clarity: get this product, check that according to " clarity test detailed rules and regulations and criterion " this product is up to specification.
Experimental example 2
This experimental example is the qualitative determination of composition in the embodiment of the invention 2 described 2ml:400mg and the 5ml:1000mg vein small-volume injection.
(1) gets the about 10ml of this product, add sulphuric acid number droplet, be cherry-red.
(2) get this product 10ml, add dilute hydrochloric acid 5ml, be heated to and boil about 3 minutes, cold slightly, regulate pH to neutral or alkaline with 10% sodium hydroxide solution, filter, add alkaline cupric tartrate test solution 1ml, the red precipitation of Red copper oxide promptly appears in heating.
Injection of the present invention is all up to specification with the inspection of beginning a project.
Experimental example 3
This experimental example is the mensuration of related substance in the embodiment of the invention 4 described 2ml:100mg and the 5ml:250mg vein small-volume injection.
Get this product, add dissolve with methanol and be diluted to the solution that every ml contains this product 5mg, as need testing solution; It is an amount of that precision takes by weighing the gastrodine reference substance, adds methanol and make the solution that contains gastrodine 5mg among every ml, in contrast product solution.Test according to thin layer chromatography (two appendix VB of Chinese Pharmacopoeia version in 2000), draw above-mentioned each μ l of two kinds of solution, point is developing solvent with chloroform-methanol (7: 3), after the expansion on same silica gel g thin-layer plate, take out, dry, spray phosphomolybdic acid test solution, toasted 5 minutes down in 105 ℃ with 10%, need testing solution and reference substance solution show the principal spot of same color, and must not show other impurity speckles.
Injection of the present invention is through three batches mensuration, and the related substance project is up to specification.
Experimental example 4
This experimental example is the embodiment of the invention 1 described 2ml:200mg and the quantitative assay of 5ml:500mg vein small-volume injection.
Precision is measured this product 2ml, puts in the 250ml measuring bottle, and thin up shakes up to scale, and precision is measured 5ml, puts in another 250ml measuring bottle, and thin up shakes up to scale, promptly makes need testing solution.In addition precision takes by weighing through 3 hours gastrodine reference substance of 105 ℃ of freeze-day with constant temperature in right amount, adds water and makes solution that every 1ml contains 16 μ g product solution in contrast.Getting above-mentioned two kinds of solution according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000), is blank with water, measures trap at 220nm wavelength place, calculates, promptly.
Injection of the present invention is through three batches assay, and gastrodin content is up to specification.
Experimental example 5
This experimental example be the embodiment of the invention 5 described 2ml:300mg and 5ml:750mg vein small-volume injection physical index quantitative assay.
Residue on ignition: check (two appendix VIIIN of Chinese Pharmacopoeia version in 2000) in accordance with the law, must not cross 0.5%.
Heavy metal: get the residue of leaving under the residue on ignition item, check to contain (two appendix VIII of Chinese Pharmacopoeia version in 2000 H, second method) heavy metal and must not cross 10/1000000ths in accordance with the law.
Injection of the present invention is through three batches mensuration, and above-mentioned project is up to specification.
Experimental example 6
This experimental example is the toxicity test of the embodiment of the invention 1 described 2ml:200mg and 5ml:500mg vein small-volume injection.
Acute toxicity testing shows: the oral or tail vein injection gastrodine of mice, dosage is used 5g/kg, observes 3 days, does not see and poisons and death.Sub-acute toxicity test shows:
Dog and mice administration were tested through sanguification after 4～6 days, and erythrocyte, leukocyte and platelet count are not had influence.
Blood testing is measured does not all have influence to glutamate pyruvate transaminase, nonprotein and cholesterol.The heart, lung, spleen, liver, kidney, stomach and intestinal with animal are made the tissue slice microscopy, do not see cytopathy.Above result shows that gastrodine does not all have influence to hemopoietic system, liver, renal function and blood fat.
The pyrogen test test shows: by " the inspection method inspection of two appendix XID of Chinese pharmacopoeia version in 2000 pyrogen, dosage is slowly injected 1ml by the every kg of rabbit body weight, and is up to specification.
Comparative example 1
The gastrodine vein small-volume injection clarity that the explanation of this comparative example is produced with process using water precipitating of the present invention, cold preservation, hyperfiltration treatment is better than producing with conventional compound method.
Table 1 method product relatively
| One adopts the technology of water precipitating, cold preservation, ultrafiltration | Two common process | |
| Method for making | A) get the fresh water for injection of 40%90 ℃ of amount of preparation, add the gastrodine in the prescription, fully stir and make dissolving fully, be placed to room temperature, 0～10 ℃ of cold preservation 24 hours, after the ultrafilter ultrafiltration with molecular cut off 100,000, the ultrafilter ultrafiltration of reuse molecular cut off 5000, get the gastrodine ultrafiltrate, the sampling detection level.B) Calcium Disodium Versenate of adding 0.04% in ultrafiltrate, content standardize solution according to gastrodine, regulate pH5.8～6.2, intermediate products after the assay was approved, with medicinal liquid through the end-filtration fill in ampoule, sterilization, lamp inspection, packing promptly gets gastrodine vein small-volume injection finished product. | A) get the fresh water for injection of 40%90 ℃ of amount of preparation, add the gastrodine in the prescription, fully stir and make dissolving fully, the Calcium Disodium Versenate of adding 0.04%, standardize solution, regulate pH5.8～6.2, intermediate products after the assay was approved, with medicinal liquid through the end-filtration fill in ampoule, sterilization, lamp inspection, packing promptly gets the gastrodine injection finished product. |
| Clarity (qualification rate is greater than 95%) | Get 200 of this product, check by " clarity test detailed rules and regulations and criterion ": 20040101 batches: only 4 have chips of glass, qualification rate 98%.20040102 batches: only 3 have chips of glass, qualification rate 98.5%.20040103 batches: only 3 have chips of glass, qualification rate 98.5%.When getting rid of fill because of the chips of glass factor of the disruptive generation of ampoule, after this PROCESS FOR TREATMENT, the clarity qualification rate reaches 100% substantially. | Get 200 of this product, check by " clarity test detailed rules and regulations and criterion ": 20040104 batches: wherein 1 has chips of glass, 9 have the small particles more than 3, qualification rate 95%.20040105 batches: wherein 2 have chips of glass, 8 have the small particles more than 3, qualification rate 95%.20040106 batches: wherein 4 have chips of glass, 6 have the small particles more than 3, qualification rate 95%.When getting rid of fill because of the chips of glass factor of the disruptive generation of ampoule, after this PROCESS FOR TREATMENT, the clarity qualification rate is between 95～97%. |
| Related substance (should accord with | Up to specification | Against regulation |
| Close regulation) | ||
| Residue on ignition (must not cross 0.5%) | 0.3％ | 0.6％ |
| Heavy metal (should be up to specification) | Up to specification | Against regulation |
| The undue toxicity | Up to specification | Up to specification |
Comparative example 2
Zest was little when the explanation of this comparative example was used clinically with the embodiment of the invention 1 described gastrodine vein small-volume injection, and untoward reaction is few.
Table 2 clinical trial relatively
| Gastrodine vein small-volume injection of the present invention | The gastrodine intravenous fluid of common process | |
| Usage and dosage | Intravenous drip, each 500～1000mg, once-a-day, with 250～500ml, use 5% glucose injection or 0.9% sodium chloride injection dilution back.Organic disease can suitably increase dosage or follow the doctor's advice. | Intravenous drip, each 500～1000mg, once-a-day, with 250～500ml.Organic disease can suitably increase dosage or follow the doctor's advice. |
| Clinical use | Treat 53 routine vascular headache patients | Treat 40 vascular headache patients |
| Untoward reaction is observed | Do not have and symptoms such as mouth and nose drying, giddy, stomach upset occur. | Symptoms such as 3 routine mouth and nose dryings, giddy, stomach upset. |
| Zest is observed | No pain phenomenon | 30 examples have the pain phenomenon, 6 routine injection site rednesses |
Comparative example 3
Treat trigeminal neuralgia patient and common process group clinically relatively:
Patient's nervi trigeminus sensation domination district has an intense pain suddenly clinically, and facial certain zone of patient is responsive especially, and touching promptly causes the pain outbreak a little, is diagnosed as trigeminal neuralgia after diagnosing.To 73 patients, treat one group of gastrodine intravenous fluid intravenous drip administration of adopting common process to produce, each 500mg, 1 time on the one respectively.One group is adopted the embodiment of the invention 1 described gastrodine vein small-volume injection intravenous drip administration, and each 500mg uses 250ml, and use 5% glucose injection dilution back, once-a-day.After treating for 1 week, have 30 people thoroughly to cure among this aspect technology group 33 routine patients on inspection, it is normal that nervi trigeminus recovers, and has 3 people still need continue treatment.Have 30 people thoroughly to cure among the common process group 40 routine patients, it is normal that nervi trigeminus recovers, and has 10 people still need continue treatment.
In sum, the embodiment of the invention 1 described gastrodine vein small-volume injection has tangible drug effect raising effect than the intravenous fluid of common process preparation.
2 groups of therapeutic outcome comparative examples of table 3 (%)
| Group | The example number | Effectively | Invalid |
| Technology group of the present invention | 33 | 30(91％) | 3(9％) |
| The common process group | 40 | 30(75％) | 10(25％) |
Claims (9)
1. gastrodine vein small-volume injection comprises gastrodine, water for injection, it is characterized in that described injection is the injection that forms through the ultra-filtration technical finesse, contains the metal chelating agent of gross weight 0.01%～0.1%.
2. gastrodine vein small-volume injection as claimed in claim 1 is characterized in that described injection contains the gastrodine of gross weight 1%～20%.
3. gastrodine vein small-volume injection as claimed in claim 1 or 2 is characterized in that described metal complex agent content is 0.03%～0.05%.
4. gastrodine vein small-volume injection as claimed in claim 1 or 2 is characterized in that described metal chelating agent is Calcium Disodium Versenate or editic acid.
5. gastrodine vein small-volume injection as claimed in claim 1 or 2 is characterized in that, described ultra-filtration is to adopt the ultrafiltration apparatus of intercepting molecular weight below 100,000 to carry out classified filtering 1～3 time.
6. the method for preparing claim 1 or 2 described gastrodine vein small-volume injections, it is characterized in that, described method comprises the steps: earlier gastrodine and an amount of 80～90 ℃ of water for injection mixed dissolutions, after being placed to room temperature, 0～10 ℃ of cold preservation 12～48 hours,, add 0.01%～0.1% metal chelating agent through 1～3 progressively filtration, ultrafiltration, last adjust pH is 5.0～7.0, and through sterilization, fill, be packaged into injection.
7. the preparation method of gastrodine vein small-volume injection as claimed in claim 6, it is characterized in that, described filtration is filtered through 1～3 time, can adopt filter paper to carry out pretreatment filters, first then ultrafiltration gets the gastrodine solution of molecular weight below 100,000, and ultrafiltration gets the gastrodine solution of molecular weight below 5000 again.
8. the preparation method of gastrodine vein small-volume injection as claimed in claim 7 is characterized in that described method comprises the steps:
A) earlier with gastrodine and an amount of 80～90 ℃ of water for injection mixed dissolutions, be placed to room temperature, 0～10 ℃ of cold preservation 12～48 hours is after the ultrafilter ultrafiltration of molecular cut off below 100,000, the ultrafilter ultrafiltration of reuse molecular cut off below 5000 gets the gastrodine ultrafiltrate;
B) in ultrafiltrate, add 0.01%～0.1% metal chelating agent, regulate pH5.0～7.0, sterilization, fill, pack injection.
9. the preparation method of gastrodine vein small-volume injection as claimed in claim 8 is characterized in that, comprises the steps:
A) earlier with gastrodine and an amount of 80～90 ℃ of water for injection mixed dissolutions, be placed to room temperature, 0～10 ℃ of cold preservation 24～32 hours is after the ultrafilter ultrafiltration of molecular cut off below 100,000, the ultrafilter ultrafiltration of reuse molecular cut off below 5000 gets the gastrodine ultrafiltrate;
B) in ultrafiltrate, add 0.03%～0.05% metal chelating agent, regulate pH5.8～6.2, sterilization, fill, pack gastrodine vein small-volume injection finished product.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510067866 CN1751691A (en) | 2004-11-26 | 2005-04-29 | Small volume intravenous injection of gastrodine and its prepn. method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200410096054.9 | 2004-11-26 | ||
| CN 200410096054 CN1634091A (en) | 2004-11-26 | 2004-11-26 | Injectio of gastrodine, its preparing process and usage |
| CN 200510067866 CN1751691A (en) | 2004-11-26 | 2005-04-29 | Small volume intravenous injection of gastrodine and its prepn. method |
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| CN1751691A true CN1751691A (en) | 2006-03-29 |
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| CN 200510067866 Pending CN1751691A (en) | 2004-11-26 | 2005-04-29 | Small volume intravenous injection of gastrodine and its prepn. method |
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| Country | Link |
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| CN (1) | CN1751691A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103156808A (en) * | 2011-12-18 | 2013-06-19 | 山东方明药业集团股份有限公司 | Gastrodin injection liquid and preparation method thereof |
| CN103520095A (en) * | 2013-10-25 | 2014-01-22 | 江西国药有限责任公司 | Gastrodin injection and preparation process thereof |
| CN106806393A (en) * | 2015-11-30 | 2017-06-09 | 湖南恒生制药股份有限公司 | Ginsenoside vein small-volume injection and preparation method thereof |
-
2005
- 2005-04-29 CN CN 200510067866 patent/CN1751691A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103156808A (en) * | 2011-12-18 | 2013-06-19 | 山东方明药业集团股份有限公司 | Gastrodin injection liquid and preparation method thereof |
| CN103520095A (en) * | 2013-10-25 | 2014-01-22 | 江西国药有限责任公司 | Gastrodin injection and preparation process thereof |
| CN103520095B (en) * | 2013-10-25 | 2015-07-01 | 江西国药有限责任公司 | Gastrodin injection and preparation process thereof |
| CN106806393A (en) * | 2015-11-30 | 2017-06-09 | 湖南恒生制药股份有限公司 | Ginsenoside vein small-volume injection and preparation method thereof |
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