CN1519246A - Salt of organic acid of cyclorrirobuxin-D, pharmaceutics and application as well as its preparation method - Google Patents
Salt of organic acid of cyclorrirobuxin-D, pharmaceutics and application as well as its preparation method Download PDFInfo
- Publication number
- CN1519246A CN1519246A CNA031323464A CN03132346A CN1519246A CN 1519246 A CN1519246 A CN 1519246A CN A031323464 A CNA031323464 A CN A031323464A CN 03132346 A CN03132346 A CN 03132346A CN 1519246 A CN1519246 A CN 1519246A
- Authority
- CN
- China
- Prior art keywords
- acid
- cyclovirobuxinum
- injection
- tartrate
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
An organic acid salt of cyclovirobuxine D in the form of injection for treating cardiovascular and cerebrovascular diseases including coronary heart disease, arrhythmia, etc. is prepared from the cyclovirobuxine D, citric acid or tartaric acid or lactic acid or butanedioic acid or methanesulfonic acid, and glucose or sodium chloride or mannitrol.
Description
Technical field
The invention belongs to a kind of new Chinese medicine, the present invention relates to the preparation method of cyclovirobuxinum D organic acid salt and preparation thereof, application and preparation.More specifically, the present invention relates to a kind of about the cyclovirobuxinum D organic acid salt, and the injection that contains them, its method for making and application thereof.
Background technology
Coronary heart disease is a kind of common cardiovascular disorder, is one of main disease that influences human health, and Incidence of CHD increased with the age, is the common disease of mid-aged population, frequently-occurring disease.In recent years, along with the quickening of social life rhythm, the change of dietary structure, cardiovascular disordeies such as coronary heart disease have become the No.1 killer of human health, select suitable medicine to treat very urgent.
Cyclovirobuxinum D (Buxine) is treatment coronary heart disease, a stenocardia, and coronary heart disease, ARR active drug, cyclovirobuxinum D claim Buxine or Ramulus Buxi Sinicae alkaloid I number etc. again; Belong to tetrahydroisoquinoline alkaloid, molecular formula is C
26H
46N
2O, according to bibliographical information, cyclovirobuxinum D, Buxine, Ramulus Buxi Sinicae alkali I number, buxine, Chinese littleleaf box element, buxine D, the evergreen Chinese littleleaf box star D of ring etc. are same monomeric compound.It is a kind of that Shang Shi preparation only has Buxine Tablet so far.But its oral onset is slow, and blood medicine peak time is long, clinically is used for light moderate patient more, so for urgency, critically ill patient, extremely doctor's the popular welcome of the treatment injection liquid of dysphagia patients.
Summary of the invention
The purpose of this invention is to provide a kind of cyclovirobuxinum D organic acid salt and preparation thereof, pass through drug administration by injection, have easy to use, rapid-action, the effective advantage such as long of holding time, can be used for urgent patients' such as coronary heart disease, stenocardia rescue and treatment, also made things convenient for the patient's of dysphagia treatment.
The organic acid salt of cyclovirobuxinum D is characterized in that the salt that cyclovirobuxinum D and acid form, and wherein acid is selected from citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid.
Cyclovirobuxinum D organic acid salt preparation, it is characterized in that with the cyclovirobuxinum D being major ingredient, cooperate citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid and glucose or sodium-chlor or N.F,USP MANNITOL to make injection, wherein the salt of Xing Chenging is cyclovirobuxinum D Citrate trianion or cyclovirobuxinum D tartrate or cyclovirobuxinum D lactic acid salt or cyclovirobuxinum D succinate and cyclovirobuxinum D mesylate.
The application of cyclovirobuxinum D organic acid salt preparation is characterized in that by intravenously administrable, the treatment cardiovascular and cerebrovascular diseases.Has promoting flow of QI and blood, the effect of removing obstruction in channels to relieve pain; The Obstruction of qi in the chest and cardialgia that is used for caused by energy stagnation and blood stasis, intermittent pulse; Coronary heart disease, irregular pulse are seen above-mentioned patient.Usage and consumption: 1 time on the one, a 1.0～3.0mg.
Cyclovirobuxinum D organic acid salt preparation is characterized in that the prescription of each component is:
Cyclovirobuxinum D 10～30mg
Glucose 30～70g
It is 3.5～6.5 that citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid are transferred pH
Water for injection adds to 1000ml
Cyclovirobuxinum D organic acid salt preparation is characterized in that the prescription of each component is:
Cyclovirobuxinum D 10～30mg
Sodium-chlor 6.0～12.0g
It is 3.5～6.5 that citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid are transferred pH
Water for injection adds to 1000ml
Cyclovirobuxinum D organic acid salt preparation is characterized in that each prescription of forming is:
Cyclovirobuxinum D 1.0～3.0g
N.F,USP MANNITOL 80～120g
It is 3.5～6.5 that citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid are transferred pH
Water for injection adds to 2000ml
The preparation method of cyclovirobuxinum D organic acid salt preparation is characterized in that:
1, takes by weighing the glucose or the sodium-chlor of recipe quantity, add that water for injection is dense joins dissolving, use charcoal absorption, filtration;
2, filtrate is injected dilute preparing tank, the cyclovirobuxinum D that takes by weighing recipe quantity adds a small amount of water for injection, adds citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid it is dissolved fully, add to the full amount of water for injection, add charcoal absorption, 70-80 ℃, insulated and stirred 15 minutes; With citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid adjust pH is 3.5～6.5;
3, filter, embedding, sterilization, promptly.
The preparation method of cyclovirobuxinum D organic acid salt preparation, it is characterized in that: the glucose of getting recipe quantity earlier carries out the dense dissolving of joining, solution is through charcoal absorption, filter, filtrate is injected dilute preparing tank, the cyclovirobuxinum D that takes by weighing recipe quantity adds a small amount of water for injection, adding citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid dissolves it fully, add to the full amount of water for injection, add charcoal absorption, pH value with citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid accent solution is 3.5～6.5, with the smart filter of the millipore filtration of 0.45 μ m, embedding, sterilization, promptly.
The preparation method of cyclovirobuxinum D organic acid salt preparation, it is characterized in that: the sodium-chlor of getting recipe quantity earlier carries out the dense dissolving of joining, solution is through charcoal absorption, filter, filtrate is injected dilute preparing tank, the cyclovirobuxinum D that takes by weighing recipe quantity adds a small amount of water for injection, adding citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid dissolves it fully, add to the full amount of water for injection, add charcoal absorption, pH value with citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid accent solution is 3.5～6.5, with the smart filter of the millipore filtration of 0.45 μ m, embedding, sterilization, promptly.
The preparation method of cyclovirobuxinum D organic acid salt preparation is characterized in that: get the recipe quantity cyclovirobuxinum D and put in the container, add a small amount of water for injection and make into pasty state, add citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid, stir and make dissolving; The N.F,USP MANNITOL that adds recipe quantity again adds injection water to 1500～1700ml; PH value to 3.5～6.5 with citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid regulator solution, add needle-use activated carbon 1～3g, stirred No. 3 sand core funnel coarse filtration 10～15 minutes, soup at sterilisable chamber through 0.45 μ m and 0.22 μ m membrane filtration degerming, washing nozzle; Water for injection is settled to 2000ml, after mensuration content and the pH value, and can, every bottle of 2ml, sabot is put in the Freeze Drying Equipment, and pre-freeze is carried out the freeze-drying operation according to freeze-drying curve, promptly to-40 ℃ under 0.06mmHg vacuum tightness.
The main pharmacodynamics of cyclovirobuxinum D (Buxine) injection, general pharmacology, toxicity and safety testing research
One, main pharmacodynamics research
The Buxine injection liquid has tangible prolongation effect to the survival time of small white mouse normal pressure hypoxia tolerance; The Acute Myocardial Infarction visceral pericardium electrocardiogram(ECG that ligation dog anterior descending coronary is caused, can reduce the unusual number that leads of ST section, obviously alleviate the degree that ∑-the ST section is unusual, the content of Serum LDH and CPK is had the trend of minimizing, can reduce ischemic myocardium and account for the percentage of flesh whole-heartedly; To the acute myocardial ischemia that ligation big white mouse arteria coroaria sinistra causes, the Buxine injection liquid can improve raising that its ST section J orders; The coronary artery of increasing and aortal volume of blood flow, increase per minute hectogram myocardial blood flow are arranged, increase cardiac output, reduction total peripheral resistance and coronary resistance, the myocardium coefficient of oxygen utilization effect of raising
Two, general pharmacology research
The Buxine injection liquid is pressed 2mg/Kg, 1mg/kg and 0.5mg/kg and is given mouse tail vein injection, to the no abnormal reaction of central nervous system of mice, the mouse activity freely, hair color is glossy, does not have and faints from fear; The Buxine injection liquid presses 2mg/kg, 1mg/kg and 0.5mg/kg gives the administration of cat intravenous injection, to cat blood pressure, breathing and electrocardiogram(ECG etc., there is no considerable change.Show that under therapeutic dose the Buxine injection liquid does not have obvious influence to central nervous system, the cardiovascular system respiratory system of unifying.
Three, acute toxicity test
Buxine injection liquid mouse tail vein injection dose regimen records LD
50Be 13.93 ± 1.68mg/kg.Intraperitoneal injection method Buxine injection liquid small white mouse medium lethal dose LD
50=107.49 ± 11.34mg/kg.
Four, long term toxicity test
1, big white mouse long term toxicity research: gave Buxine injection liquid 15mg/kg (amount to into cyclovirobuxinum D, down with), 7.5mg/kg and 3.75mg/kg 3 months for the continuous abdominal injection of Wistar rat.The result: duration of test, Buxine injection liquid 15mg/kg group after 1 month, sees that animal wool is fluffy in administration, activity reduces, body weight gain is slow, other each treated animal activities freely, stool and urine is normal, body weight increases naturally.3 months and each animal hematology inspection discovery of decubation after the administration: Buxine injection liquid 15mg/kg liver function has infringement in various degree, and other each groups show no obvious abnormalities; The coefficient of important organ: the coefficient of 15mg/kg animal livers increases; Histopathologic examination: administration 3 months: Buxine injection liquid 15mg/kg group: the 1 example time focal inflammation of lung; The inferior liver cell spotty necrosis that occurs of 2 examples; Bile capillary hyperplasia between the leaflet of hepatic portal area under control: severe 7 examples are inferior, and moderate 2 examples are inferior, slight 1 routine time; Hepatic fibrosis: moderate 3 examples are inferior, and slight 2 examples are inferior.Buxine injection liquid 7.5mg/kg group: bile capillary hyperplasia between the leaflet of hepatic portal area under control: moderate 3 routine times, slight 2 examples are inferior, hepatic fibrosis: slight 1 example is inferior.Buxine injection liquid 3.75mg/kg group and blank group and all the other animal visceras comprise brain, optic nerve, hypophysis, the heart, liver, spleen, pancreas, lung, tracheae, kidney, suprarenal gland, thymus gland, Tiroidina, bladder, testis, epididymis, prostate gland, uterus, ovary, stomach, intestines etc., do not find that all obvious pathologic changes.Decubation: Buxine injection liquid 15mg/kg group: bile capillary hyperplasia between the leaflet of hepatic portal area under control: moderate 3 examples are inferior, and slight 1 example is inferior; Fibrous tissue moderate hyperplasia 2 examples are inferior, and slight 1 example is inferior.Buxine injection liquid 7.5mg/kg group: slight 1 example of bile capillary is inferior between the leaflet of hepatic portal area under control.3.75mg/kg group and blank group and all the other animal visceras comprise brain, optic nerve, hypophysis, the heart, liver, spleen, pancreas, lung, tracheae, kidney, suprarenal gland, thymus gland, Tiroidina, bladder, testis, epididymis, prostate gland, uterus, ovary, stomach, intestines etc., do not find that all obvious pathologic changes.
According to results such as animal generalized case, hematological examination, important organ pathological examinations as can be seen, the safe dose of the long-term intraperitoneal injection of Buxine injection liquid big white mouse should be below 3.75mg/kg (be equivalent to the clinical consumption of people 112.5 times).
2, Beagle dog long term toxicity research:
Amounted to cyclovirobuxinum D 6mg/kg, 3mg/kg and 1.5mg/kg three months for Beagle dog continuous intravenous injection Buxine injection liquid.The result: duration of test, after the each administration of Buxine injection liquid high dose group animal about 10-20 minute, animal all appearance activity reduced, and reposes, and generally continues about 30-60 minute; Other animal activity freely, stool and urine is normal, body weight increases naturally.Electrocardioscopy: 6mg/kg and 3mg/kg group has block in various degree, shows as: the P-R interval, prolongs, and the rhythm of the heart slows down with uneven.When experiment finished, laboratory examination is found: 6mg/kg treated animal routine blood test index was normal, but blood parameters AST, the ALP of part animal raise; 3mg/kg, 1.5mg/kg group and blank treated animal hematology and routine urianlysis are normal substantially.The liver coefficient of the coefficient of important organ: 6mg/kg group increases; Other organ coefficient is normal.Pathological examination is found: the blank group: the sample sex change of loosening of 1 routine liver cell.Buxine injection liquid (6mg/kg): 2 routine liver cell moderate cavity sample sex change, the 1 routine liver cell moderate sample sex change of loosening, 1 routine myofibrosis cordis; Buxine injection liquid (3mg/kg): the sample sex change of loosening of 1 routine liver cell moderate, the 1 routine slight hepatic cell sample sex change of loosening; Buxine injection liquid (1.5mg/kg) and blank group and all the other animal visceras comprise brain, hypophysis, optic nerve, the heart, liver, spleen, lung, kidney, pancreas, tracheae, suprarenal gland, thymus gland, Tiroidina, prostate gland, testis, epididymis, uterus, ovary, stomach, intestines etc., do not find that all obvious pathologic changes.Decubation is checked and finds: the every index of hematology and routine urianlysis is all in normal range; Electrocardiogram(ECG is substantially in normal range; Pathological examination is found: decubation Buxine injection liquid (6mg/kg) group has the sample sex change of loosening of 1 routine slight hepatic cell; Decubation Buxine injection liquid (3mg/kg, 1.5mg/kg) and each internal organs of blank group comprise brain, hypophysis, optic nerve, the heart, liver, spleen, lung, kidney, pancreas, tracheae, suprarenal gland, thymus gland, Tiroidina, prostate gland, testis, epididymis, uterus, ovary, stomach, intestines etc., do not find that all obvious pathologic changes.
In sum, the Buxine injection liquid is given Beagle dog intravenous injection 1.5mg/kg3 month continuously, and dog can tolerate substantially, tangible toxic reaction do not occur; But continuous intravenous injection 6mg/kg (the clinical consumption of people 180 times) and 3mg/kg (the clinical consumption of people 90 times) are in the time of 3 months, toxic reaction in various degree just appears in animal, mainly show as: blood biochemical is learned and is checked discovery, serum AST, ALP raise, the existing block in various degree of Electrocardiogram, heart rate is slow, and the P-R interval prolongs arrhythmia etc.; Pathological examination finds that the infringement in various degree of many internal organs is arranged, and is mainly liver, although 15 days most abnormal indexes can recover normally still to note the variation of electrocardiogram(ECG and liver function during administration after the drug withdrawal.
Five, cyclovirobuxinum D (Buxine) glucose injection safety testing
1, the Buxine glucose injection is given rabbit vein 5.0ml/kg (concentration: contain Buxine 0.02mg/ml) 5 days, and the blood vessel of rabbit is not seen tangible irritative response.
2, the Buxine glucose injection attacks for guinea pig intraperitoneal injection sensitization three times and intravenous injection in 14 days, 21 days, and cavy does not see tangible anaphylaxis.
3, the Buxine glucose injection does not have tangible haemolysis and agglutination external to tame rabbit erythrocyte.
Six, cyclovirobuxinum D (Buxine) sodium chloride injection safety testing
1, the Buxine sodium chloride injection is given rabbit vein 5.0ml/kg (concentration: contain Buxine 0.02mg/ml) 5 days, and the blood vessel of rabbit is not seen tangible irritative response.
2, the Buxine sodium chloride injection attacks for guinea pig intraperitoneal injection sensitization three times and intravenous injection in 14 days, 21 days, and cavy does not see tangible anaphylaxis.
3, the Buxine sodium chloride injection does not have tangible haemolysis and agglutination external to tame rabbit erythrocyte.
Seven, hydrochloride for injection cyclovirobuxinum D safety testing
1, the hydrochloride for injection cyclovirobuxinum D is given rabbit vein 5.0ml/kg (concentration: contain Buxine 0.02mg/ml) 5 days, and the blood vessel of rabbit is not seen tangible irritative response.
2, the hydrochloride for injection cyclovirobuxinum D attacks for guinea pig intraperitoneal injection sensitization three times and intravenous injection in 14 days, 21 days, and cavy does not see tangible anaphylaxis.
3, the hydrochloride for injection cyclovirobuxinum D does not have tangible haemolysis and agglutination external to tame rabbit erythrocyte.
Embodiment
Example 1:
The method for making of cyclovirobuxinum D (Buxine) glucose injection
One, prescription:
Cyclovirobuxinum D 20mg
Glucose 50g
Citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid are an amount of
Water for injection adds to 1000ml
Two, preparation technology
1, prepare: infusion bottle, plug, terylene lining form be processing, standby routinely respectively; Pipeline, container are cleared out a gathering place totally standby.
2, get glucose, add to the full amount of water for injection 1/5, add gac (2/10000ths g/ml) and boiled 15 minutes, leach gac, pump into dilute preparing tank, the cyclovirobuxinum D that takes by weighing recipe quantity adds a small amount of water for injection, add citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid it is dissolved fully, add to the full amount of water for injection, add gac (2/10000ths g/ml), 70-80 ℃, insulated and stirred 15 minutes; With citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid adjust pH.
3, measure the pH value 3.5-6.5 of solution.
4, measure the content of solution.
5, all qualified back of the pH value of solution and content filter to clarity with the millipore filtration essence of 0.45 μ m qualified, embedding.
6,115 ℃ of pressure sterilizings are 30 minutes.
7, lamp inspection, packing, warehouse-in.
Example 2:
The method for making of cyclovirobuxinum D (Buxine) sodium chloride injection
One, prescription:
Cyclovirobuxinum D 20mg
Sodium-chlor 9.0g
Citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid are an amount of
Water for injection adds to 1000ml
Two, preparation technology
1, prepares
After the used pipeline of dosing, the utensil conventional processing, clean with the water for injection washing; Infusion bottle, plug, terylene lining form be processing, standby routinely respectively.
2, dosing
[1] get the sodium-chlor of recipe quantity, add water for injection, stir and make dissolving, add the needle-use activated carbon of 0.02% (w/v) simultaneously, stir, boiled 15 minutes, filter with diameter 0.8 μ m millipore filtration to 1/5 of full dose, standby;
[2] above-mentioned sodium chloride solution is pumped into dilute preparing tank, the cyclovirobuxinum D that takes by weighing recipe quantity adds a small amount of water for injection, adding citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid makes it dissolve fully in right amount, add to the full amount of water for injection, add gac 0.02% (w/v), stir evenly, be heated to 70-80 ℃, insulated and stirred 15 minutes is with citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid accent pH to 3.5-6.5.
3, measure intermediate pH value and content.
4, pH value and after the assay was approved, extremely clear and bright with diameter 0.45 μ m filtering with microporous membrane.
5, with above-mentioned liquid medicine filling, sealing by fusing.
6,115 ℃ of pressure sterilizings 30 minutes, leak detection.
7, lamp inspection, packing, warehouse-in.
Example 3:
The method for making of hydrochloride for injection cyclovirobuxinum D
One, prescription:
Cyclovirobuxinum D 2.0g
N.F,USP MANNITOL 100g
Citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid are an amount of
Water for injection adds to 2000ml
Make 1000 bottles altogether
Two, preparation technology
Aseptic technique: measure cyclovirobuxinum D by prescription and put in the container, add a small amount of water for injection and make into pasty state, adding citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid are an amount of, stir and make dissolving; The N.F,USP MANNITOL that adds recipe quantity again adds the injection water to 1600ml; With the pH value of citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid regulator solution to 3.5-6.5, add needle-use activated carbon 2g, stirred 10～15 minutes, No. 3 sand core funnel coarse filtration, with an amount of water for injection washing nozzle, soup at sterilisable chamber through 0.45 μ m and 0.22 μ m membrane filtration degerming, with an amount of water for injection washing nozzle.Water for injection is settled to 2000ml, after mensuration content and the pH value, and can, every bottle of 2ml, sabot is put in the Freeze Drying Equipment, and pre-freeze is carried out freeze-drying operation according to freeze-drying curve to-40 ℃ under 0.06mmHg vacuum tightness.After the freeze-drying, get the loose bulk sample of off-white color, fill in plug, roll aluminium lid promptly.
Claims (10)
1, the organic acid salt of cyclovirobuxinum D is characterized in that the salt that cyclovirobuxinum D and acid form, and wherein acid is selected from citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid.
2, cyclovirobuxinum D organic acid salt preparation according to claim 1, it is characterized in that with the cyclovirobuxinum D being major ingredient, cooperate citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid and glucose or sodium-chlor or N.F,USP MANNITOL to make injection, wherein the salt of Xing Chenging is cyclovirobuxinum D Citrate trianion or cyclovirobuxinum D tartrate or cyclovirobuxinum D lactic acid salt or cyclovirobuxinum D succinate and cyclovirobuxinum D mesylate.
3, the application of cyclovirobuxinum D organic acid salt preparation according to claim 2 is characterized in that by intravenously administrable, the treatment cardiovascular and cerebrovascular diseases; Has promoting flow of QI and blood, the effect of removing obstruction in channels to relieve pain; The Obstruction of qi in the chest and cardialgia that is used for caused by energy stagnation and blood stasis, intermittent pulse; Coronary heart disease, irregular pulse are seen above-mentioned patient; Usage and consumption: 1 time on the one, a 1.0～3.0mg.
4, cyclovirobuxinum D organic acid salt preparation according to claim 2 is characterized in that the prescription of each component is:
Cyclovirobuxinum D 10～30mg
Glucose 30～70g
It is 3.5～6.5 that citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid are transferred pH
Water for injection adds to 1000ml
5, cyclovirobuxinum D organic acid salt preparation according to claim 2 is characterized in that the prescription of each component is:
Cyclovirobuxinum D 10～30mg
Sodium-chlor 6.0～12.0g
It is 3.5～6.5 that citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid are transferred pH
Water for injection adds to 1000ml
6, cyclovirobuxinum D organic acid salt preparation according to claim 2 is characterized in that each prescription of forming is:
Cyclovirobuxinum D 1.0～3.0g
N.F,USP MANNITOL 80～120g
It is 3.5～6.5 that citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid are transferred pH
Water for injection adds to 2000ml
7, the preparation method of cyclovirobuxinum D organic acid salt preparation according to claim 2 is characterized in that:
(1) takes by weighing the glucose or the sodium-chlor of recipe quantity, add that water for injection is dense joins dissolving, use charcoal absorption, filtration;
(2) filtrate is injected dilute preparing tank, the cyclovirobuxinum D that takes by weighing recipe quantity adds a small amount of water for injection, adds citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid it is dissolved fully, add to the full amount of water for injection, add charcoal absorption, 70-80 ℃, insulated and stirred 15 minutes; With citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid adjust pH is 3.5～6.5;
(3) filter, embedding, sterilization, promptly.
8, according to claim 2,4, the preparation method of 7 described cyclovirobuxinum D organic acid salt preparations, it is characterized in that: the glucose of getting recipe quantity earlier carries out the dense dissolving of joining, solution is through charcoal absorption, filter, filtrate is injected dilute preparing tank, the cyclovirobuxinum D that takes by weighing recipe quantity adds a small amount of water for injection, adding citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid dissolves it fully, add to the full amount of water for injection, add charcoal absorption, pH value with citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid accent solution is 3.5～6.5, with the smart filter of the millipore filtration of 0.45 μ m, embedding, sterilization, promptly.
9, according to claim 2,5, the preparation method of 7 described cyclovirobuxinum D organic acid salt preparations, it is characterized in that: the sodium-chlor of getting recipe quantity earlier carries out the dense dissolving of joining, solution is through charcoal absorption, filter, filtrate is injected dilute preparing tank, the cyclovirobuxinum D that takes by weighing recipe quantity adds a small amount of water for injection, adding citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid dissolves it fully, add to the full amount of water for injection, add charcoal absorption, pH value with citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid accent solution is 3.5～6.5, with the smart filter of the millipore filtration of 0.45 μ m, embedding, sterilization, promptly.
10, according to the preparation method of claim 2,6 described cyclovirobuxinum D organic acid salt preparations, it is characterized in that: get the recipe quantity cyclovirobuxinum D and put in the container, add a small amount of water for injection and make into pasty state, add citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid, stir and make dissolving; The N.F,USP MANNITOL that adds recipe quantity again adds injection water to 1500～1700ml; PH value to 3.5～6.5 with citric acid or tartrate or lactic acid or Succinic Acid and methylsulfonic acid regulator solution, add needle-use activated carbon 1～3g, stirred No. 3 sand core funnel coarse filtration 10～15 minutes, soup at sterilisable chamber through 0.45 μ m and 0.22 μ m membrane filtration degerming, washing nozzle; Water for injection is settled to 2000ml, after mensuration content and the pH value, and can, every bottle of 2ml, sabot is put in the Freeze Drying Equipment, and pre-freeze is carried out the freeze-drying operation according to freeze-drying curve, promptly to-40 ℃ under 0.06mmHg vacuum tightness.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031323464A CN1519246A (en) | 2003-08-15 | 2003-08-15 | Salt of organic acid of cyclorrirobuxin-D, pharmaceutics and application as well as its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031323464A CN1519246A (en) | 2003-08-15 | 2003-08-15 | Salt of organic acid of cyclorrirobuxin-D, pharmaceutics and application as well as its preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1519246A true CN1519246A (en) | 2004-08-11 |
Family
ID=34286031
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031323464A Pending CN1519246A (en) | 2003-08-15 | 2003-08-15 | Salt of organic acid of cyclorrirobuxin-D, pharmaceutics and application as well as its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1519246A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100376596C (en) * | 2006-03-13 | 2008-03-26 | 杭太俊 | Buxine, buxine hydrochloride, and its preparing method and formulation |
| CN101012266B (en) * | 2007-02-14 | 2010-05-19 | 东南大学 | Large-scale industrialization preparation method for cyclovirobuxinum C |
-
2003
- 2003-08-15 CN CNA031323464A patent/CN1519246A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100376596C (en) * | 2006-03-13 | 2008-03-26 | 杭太俊 | Buxine, buxine hydrochloride, and its preparing method and formulation |
| CN101012266B (en) * | 2007-02-14 | 2010-05-19 | 东南大学 | Large-scale industrialization preparation method for cyclovirobuxinum C |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1314396C (en) | Application of levoornidazole in preparation of anti anaerobic bacteria infection medicine | |
| CN101053550A (en) | Rhizoma Gastrodiae nasal gel preparation | |
| CN101033245A (en) | Preparation method and application of pedunculoside | |
| CN101032512A (en) | Medicine composition for expanding blood volume and the preparing method thereof | |
| CN1931874A (en) | Prepn process, medicine prepn and medicinal use of ginseng glycopeptide | |
| CN1686441A (en) | Chinese medicine capsule used for regulating immunity, its preparation method and use | |
| CN1519246A (en) | Salt of organic acid of cyclorrirobuxin-D, pharmaceutics and application as well as its preparation method | |
| CN1429558A (en) | Mannosan peptide injection and its preparation and use method | |
| CN1268323C (en) | Rhodiola sacra soft capsule and its preparation | |
| CN100337629C (en) | Milrinone sodium chloride injection and production thereof | |
| CN1435428A (en) | Cyclovirobuxine D salt and its preparation and use, and process for preparing said preparation | |
| CN1772020A (en) | Freeze dried pubescent holly powder for injection and its prepn | |
| CN1895540A (en) | Medicinal composition for treating cardiovascular disease, its making method and use | |
| CN1272026C (en) | Medicinal composition for treating cardiocerebral vasculr disease and its preparing method | |
| CN101032534A (en) | Method of preparing jiubiying total saponins and the application thereof | |
| CN1739502A (en) | Application of benzydalysine in preparing medicine for treating diabetic peripheral neuropathy | |
| CN1636581A (en) | Safflower medicine composition and its prepn process and use | |
| CN1224396C (en) | Pharmaceutical for treating cardiovascular and cerebrovascular disease | |
| CN1526401A (en) | Medicine composition for treating coronary heart disease and its prepn process, use and guality control method | |
| CN1569196A (en) | Rhodiola sacra injection and its preparation | |
| CN1247196C (en) | Solid prepn. of sodium vitamin C for injection and its prepn. method | |
| CN1582946A (en) | Use of centellosic acid derivative in preparation of medicines for diseases of cardio-cerebral blood vessels | |
| CN1240394C (en) | Medication for anti ischemia and reperfusion damage | |
| CN1277554A (en) | Use of glycosaminoglycans for producing pharmaceutical preparations for treating diabetes-associated diseases of the eye | |
| CN107951885B (en) | A kind of combination of oral medication for treating capillary leak syndrome |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |