CN100418518C - Injectable diacetylamino acetic ethylenediamine prepn. preparing method and quality-control tech. therefor - Google Patents
Injectable diacetylamino acetic ethylenediamine prepn. preparing method and quality-control tech. therefor Download PDFInfo
- Publication number
- CN100418518C CN100418518C CNB200510039248XA CN200510039248A CN100418518C CN 100418518 C CN100418518 C CN 100418518C CN B200510039248X A CNB200510039248X A CN B200510039248XA CN 200510039248 A CN200510039248 A CN 200510039248A CN 100418518 C CN100418518 C CN 100418518C
- Authority
- CN
- China
- Prior art keywords
- injection
- ethylenediamine
- preparation
- water
- acetic acid
- 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.)
- Expired - Fee Related
Links
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention discloses a diethylamide ethylenediamine preparation for injection, and a preparation method and a quality control technique thereof. The preparation is prepared into an injection liquid or a freeze-dried power by diethylamide acetic acid ethylenediamine and water for injection. By the clinical application, the injectable diethylamide acetic acid ethylenediamine has good curative effects on hemorrhage caused by various reasons, and can prevent the hemorrhage caused by various reasons.
Description
Technical field
What the present invention announced is a kind of preparation method and Quality Control Technology of hemorrhage, is the preparation method and the Quality Control Technology of injection diacetyl ammonia ethylenediamine specifically.
Background technology
Nearly 5000 milliliters of blood in the human body, when the amount of bleeding that causes when a variety of causes surpasses 15% (about 750 milliliters) of whole body blood volume, the patient will occur dizziness, weakness, thirsty, limbs are clammy and blood pressure is on the low side.When hemorrhage 30%～50% (about 1500～2500 milliliters) that surpass the total blood volume of whole body can produce shock, show as that dysphoria or obnubilation, the limbs being moist and cold, dyspnea, blood pressure lower (systolic pressure is lower than 80 millimetress of mercury), pulse is fast and a little less than, treat as untimely, with serious threat patient's life.When causing bleeding, drug application hemostasis in time is one of important measures at a variety of causes (work damage, disease, operation, wound).Diacetyl nitrilo acetic acid ethylenediamine is a clinical practice hemorrhage safely and effectively, and its mechanism of action is: (1) inhibition plasminogen can not activate and be fibrinolysin, thereby suppresses fibrinous dissolving, produces anastalsis.(2) promote the platelet release of active agent, strengthen hematoblastic aggregation and adhesiveness, shorten clotting time, produce anastalsis.(3) strengthen capillary resistance, reduce the permeability of blood capillary, thereby reduce hemorrhage.Diacetyl nitrilo acetic acid ethylenediamine produces anastalsis by influencing each link of coagulation process, thereby the hemorrhage of ratio single effect in the past is rapider, curative effect is more definite, can be used for preventing and treating hemorrhage that a variety of causes causes.
Summary of the invention
Preparation of ethylenediamine diaceturate for injection is characterized in that in following ratio preparation:
Diacetyl nitrilo acetic acid ethylenediamine 150 ~ 200g (presses C
10H
22N
4O
6100%)
Water for injection 2000ml.
The preparation method of described preparation of ethylenediamine diaceturate for injection, it is characterized in that: take by weighing diacetyl nitrilo acetic acid ethylenediamine 150 ~ 200g, to sterile chamber, add injection water 1000ml, stirring and dissolving adds activated carbon adsorption impurity, with 0.45 μ m microporous filter membrane device filtering decarbonization, add water for injection to 2000ml, 0.22 μ m microporous filter membrane device of reuse sterilization filters, and the filtrate packing promptly gets injects liquor; With the filtrate frozen drying, get freeze-dried powder preparation.
Described preparation method, it is characterized in that: take by weighing diacetyl nitrilo acetic acid ethylenediamine 200g, to sterile chamber, add injection water 1000ml, stirring and dissolving, add 0.25～0.1g active carbon, stirred 30 minutes, and, added water for injection to 2000ml with 0.45 μ m microporous filter membrane device filtering decarbonization, 0.22 μ m microporous filter membrane device of reuse sterilization filters, and packing promptly gets and injects liquor after the filtrate passed examination; With the filtrate frozen drying, adopt one time the sublimation drying method, in pharmaceutical freeze dryers, carry out, with goods solution precooling in hothouse of anticipating, the pre-freeze temperature is-25 ℃～-45 ℃, the pre-freeze time is 2～6 hours, the cold preservation indoor temperature is dropped to-50 ℃ simultaneously, starts vacuum pump, treat vacuum reach 10mmHg following after, slowly open valve, close fridge below the 0.1mmHg when vacuum in the hothouse reaches, slowly heat, kept this temperature 20～30 hours to-20 ℃, treat the water evaporates ashes, slowly heat up, change drying again at 40 ℃, be 3～10 hours drying time again, total time spent of whole dry run is 25～46 hours, promptly gets lyophilized formulations.
Described preparation method, it is characterized in that: take by weighing diacetyl nitrilo acetic acid ethylenediamine 200g, to sterile chamber, add injection water 1000ml, stirring and dissolving, add 0.25～0.1g active carbon, stirred 30 minutes, and, added water for injection to 2000ml with 0.45 μ m microporous filter membrane device filtering decarbonization, 0.22 μ m microporous filter membrane device of reuse sterilization filters, and packing promptly gets and injects liquor after the filtrate passed examination; With the filtrate frozen drying, adopt one time the sublimation drying method, with goods solution precooling in hothouse of anticipating, the pre-freeze temperature is-30 ℃～-40 ℃, the pre-freeze time is 4～5 hours, the cold preservation indoor temperature is dropped to-50 ℃ simultaneously, start vacuum pump, after treating that vacuum reaches below the 10mmHg, slowly open valve, close fridge below the 0.1mmHg when vacuum in the hothouse reaches, slowly heat to-20 ℃, kept this temperature 23～28 hours, and treated water evaporates ashes (water content is reduced to below 8%), slowly heat up, change over to drier at 40 ℃, be 5～8 hours drying time again, and total time spent of whole dry run is 32～41 hours, promptly gets lyophilized formulations.
Described preparation method, it is characterized in that: take by weighing diacetyl nitrilo acetic acid ethylenediamine 200g, to sterile chamber, add injection water 1000ml, stirring and dissolving, add the 0.5g active carbon, stirred 30 minutes, and, added water for injection to 2000ml with 0.45 μ m microporous filter membrane device filtering decarbonization, 0.22 μ m microporous filter membrane device of reuse sterilization filters, and packing promptly gets and injects liquor after the filtrate passed examination; The filtrate frozen drying is adopted a sublimation drying method, the goods solution of anticipating is dry indoor precooling, the pre-freeze temperature is-40 ℃, the pre-freeze time is 5 hours, the cold preservation indoor temperature is dropped to-50 ℃ simultaneously, starts vacuum pump, treat vacuum reach 10mmHg following after, slowly open valve, close fridge below the 0.1mmHg when vacuum in the hothouse reaches, slowly heat, kept this temperature 25 hours to-20 ℃, treat water evaporates ashes (water content is reduced to below 8%), slowly heat up, change drying again at 40 ℃, be 5 hours drying time again, total time spent of whole dry run is 35 hours, promptly gets lyophilized formulations.
The Quality Control Technology of preparation of ethylenediamine diaceturate for injection is characterized in that differentiating by the following method and measuring:
[discriminating]
(1) gets preparation of ethylenediamine diaceturate for injection an amount of (being equivalent to diacetyl nitrilo acetic acid ethylenediamine 10mg approximately), add 1 of potassium iodide test solution and 4% potassium iodate solution 0.5ml, put in the water-bath and heated 1 minute, cooling, add 1～4 of starch indicator solution, it is blue that solution shows;
(2) get preparation of ethylenediamine diaceturate for injection an amount of (being equivalent to diacetyl nitrilo acetic acid ethylenediamine 10mg approximately), add saturated propylene glycol salt manufacturing acid azanol 1ml, little fiery heated and boiled 3 minutes adds 1 of ferric chloride test solution after the cooling, and solution shows brownish red;
(3) get preparation of ethylenediamine diaceturate for injection an amount of (being equivalent to diacetyl nitrilo acetic acid ethylenediamine 10mg approximately), added the ninhydrin solution heated and boiled 2 minutes, it is brown that solution shows;
[inspection]
The clarity of solution and color
Get 5 bottles of preparation of ethylenediamine diaceturate for injection, after the water 2ml dissolving, solution should be clarified respectively; As showing muddy, compare with No. 1 turbidity standard (two appendix IX of Chinese Pharmacopoeia version in 2000 B), all must not be denseer; As colour developing, compare with yellow or No. 2 standard color solutions of yellow green (two appendix IX of Chinese Pharmacopoeia version in 2000 A, first method), all must not be darker;
Loss on drying
Get preparation of ethylenediamine diaceturate for injection, be dried to constant weight, subtract weight loss and must not cross 5.0% (Chinese Pharmacopoeia version appendix in 2000 VIII L) at 105 ℃;
Acidity
It is an amount of to get preparation of ethylenediamine diaceturate for injection, adds water and makes the solution that contains 0.1g among every 1ml, measures (two appendix VI of Chinese Pharmacopoeia version in 2000 H) in accordance with the law, and pH value should be 5.0～6.5;
Aseptic
Get preparation of ethylenediamine diaceturate for injection, add aquesterilisa 2ml dissolving respectively, check (Chinese Pharmacopoeia version appendix in 2000 XI H) in accordance with the law, should be up to specification;
Bacterial endotoxin
Get preparation of ethylenediamine diaceturate for injection, check (two appendix XI of Chinese Pharmacopoeia version in 2000 E) in accordance with the law, containing the endotoxin amount among every 1mg should be less than 0.125EU;
Other should meet every regulation relevant under the injection item (Chinese Pharmacopoeia version appendix in 2000 I B);
[assay]
Precision is measured preparation of ethylenediamine diaceturate for injection an amount of (being equivalent to diacetyl nitrilo acetic acid ethylenediamine 0.2g approximately), after adding water 2ml dissolving, add the thymolphthalein indicator solution is shown neutral pyridine 20ml, add thymolphthalein indicator solution number droplet, with sodium hydroxide volumetric solution (0.1mol/L) titration; Every 1ml sodium hydroxide volumetric solution (0.1mol/L) is equivalent to the C of 14.72mg
10H
22N
4O
6
The present invention prepares freeze-dried powder preparation and carries out in pharmaceutical freeze dryers, pharmaceutical freeze dryers mainly by drying baker, vacuum system, refrigeration system, cold-trap system, heating system, add that convering system, automatic control system etc. are several most of to be become.In addition, big-and-middle-sized freezer dryer also often has steam sterilization system (SIP), purging system on the throne (CIP).
Refrigeration system is respectively freeze drying box and the cold-trap system provides low-temperature receiver.The single-stage refrigerant compression circulation flaggy cryogenic temperature that adopts is between-35 ℃～-40 ℃ at present, and condenser temperature is about-50 ℃; The flaggy cryogenic temperature of two-stage refrigeration compression cycle is between-45 ℃～-50 ℃, and condenser temperature is about-65 ℃; Cascade refrigeration circulation flaggy cryogenic temperature is between-55 ℃～-60 ℃, and condenser temperature is about-75 ℃.
The control of freezer dryer mainly is start-stop and the temperature controlling to refrigeration machine, vacuum unit, heating power, to the mensuration of vacuum, temperature, monitoring and protection automatically, alarm device etc.The freeze dryer of employing Automatic Control or microcomputerized control can both show the duty of each critical piece, shows temperature, vacuum, the water vessel temperature of interior shelf of drying baker and medicine, can both carry out parameter setting, modification and demonstration in real time.
Pharmaceutical freeze dryers must be carried out the GMP codes and standards, realizes height asepticize, dustlessization, reaches highly reliable, safety, easy maintenance.Pharmaceutical freeze dryers often adopts steam sterilization system (SIP) to guarantee that sterilization is thorough, no dead angle for this reason.Be aided with purging system on the throne (CIP) simultaneously, hothouse, condenser, main valve and pipeline are carried out the default discharge opeing gradient of clean-in-place, guarantee the no liquid delay.Have simultaneously that reply has a power failure, cuts off the water, the protective measure of maloperation,, can carry out medicine and protect in case break down; Realize the computer control of freeze dryer operation operation, have three Counter Measures Dispensing Systems of cutting off the water, can report to the police automatically by the multichannel interlocking.
Pharmacological research
1, suppresses activator of plasminogen, plasminogen can not be activated be fibrinolysin, thereby suppress fibrinous dissolving, produce anastalsis.
2, promote the platelet release of active agent, strengthen hematoblastic aggregation and adhesiveness, shorten clotting time, produce anastalsis.
3, strengthen capillary resistance, reduce the permeability of blood capillary, thereby reduce hemorrhage.
The specific safety experiment
1, the obvious stimulation reaction is not seen in the intramuscular injection of injection diacetyl nitrilo acetic acid ethylenediamine rabbit.
2, injection diacetyl nitrilo acetic acid ethylenediamine rabbit vein instils does not have the obvious stimulation effect to blood vessel.
3, injection diacetyl nitrilo acetic acid ethylenediamine does not cause the Cavia porcellus anaphylaxis.
4, injection diacetyl nitrilo acetic acid ethylenediamine does not cause haemolysis and agglutination.
Toxicological study
The intravenous LD of preparation of ethylenediamine diaceturate for injection white mice
50Be 683.3mg/kg, preparation of ethylenediamine diaceturate for injection safety is described, toxicity is low.
Clinical research
Diacetyl nitrilo acetic acid ethylenediamine through clinical practice not only to a variety of causes cause hemorrhage, better curative effect is all arranged.Simultaneously can also prevent a variety of causes hemorrhage.Be mainly used in following several hemorrhage:
(1) digestive tract hemorrhage: large bolus injection diacetyl nitrilo acetic acid ethylenediamine can effectively be treated acute bleeding profusely rapidly, and can solve patient's oral medication problem of difficult under the situation of jeopardizing.Diacetyl nitrilo acetic acid ethylenediamine not only can stop blooding rapidly to acute hemorrhage of upper gastrointestinal tract, and low dose of application diacetyl nitrilo acetic acid ethylenediamine has a definite curative effect to the chronic digestible road is hemorrhage.
(2) ophthalmorrhagia: ophthalmorrhagia comprises that eyelid is hemorrhage, conjunctival hemorrhage, cornea (interior) is hemorrhage, eye socket is hemorrhage, optic nerve hemorrhage, hyphema, vitreous humour are hemorrhage, iridemia, corpus ciliare are hemorrhage, choroidal hemorrhage, retinal hemorrhage etc.Because of bleeding part and different in kind, different symptoms such as visual disorder, diplopia, pain, photophobia can appear.In the treatment, in the time of etiological treatment, cooperate diacetyl nitrilo acetic acid ethylenediamine curative effect better.
(3) epistaxis: claim epistaxis again, be the hals,Nasen und Ohrenheilkunde common disease.There is report that 46 examples (30 routine bilaterals, 16 examples are one-sided, amount to 76 sides) nasal polyp patient with operation postoperative is used the intravenous drip of diacetyl nitrilo acetic acid ethylenediamine, produce effects 59 sides as a result, effective 15 sides, total effective rate 97.37%.
(4) gynecological bleeding: very common clinically, account for gynecological's outpatient service, inpatient's 1/3.Gynecology hemorrhagic disease sickness rate height has a strong impact on body of women health.Diacetyl nitrilo acetic acid ethylenediamine and thrombinogen effect form thrombin, can strengthen capillary resistance simultaneously, reduce capillary permeability, so preparation of ethylenediamine diaceturate for injection is applicable to gynecological's hemostasis.
(5) cranium cerebral hemorrhage: the Infant Mortality of cerebral hemorrhage is very high, has the half patient dead in the morbidity a few days approximately, most sequela that leave in various degree in the survivor.Therefore cerebral hemorrhage should actively use the hemorrhage treatment, and it is better in time to inject the prognosis of diacetyl nitrilo acetic acid ethylenediamine.
(6) other: to operation oozing of blood, urinary tract are hemorrhage good efficacy arranged all.
Untoward reaction
The untoward reaction that may occur has giddy, decreased heart rate, weak, skin numbness, heating sense, xerostomia, vomiting, feels sick etc.Big multipotency die away or drug withdrawal after can disappear.
Description of drawings
Accompanying drawing is a process chart of the present invention.
The specific embodiment:
1, prescription;
Diacetyl nitrilo acetic acid ethylenediamine 200g (presses C
10H
22N
4O
6100%)
Water for injection 2000ml
Make 1000 bottles
2, method for making:
Take by weighing diacetyl nitrilo acetic acid ethylenediamine 200g, to sterile chamber, add injection water 1000ml, stirring and dissolving, add the 0.5g active carbon, stirred 30 minutes, with microporous filter membrane (0.45 μ m) device filtering decarbonization, add water for injection to capacity (2000ml), microporous filter membrane (the 0.22 μ m) device of reuse sterilization filters, and is sub-packed in the control antibiotic glass bottle of 10ml every bottle of fill 2ml after the filtrate passed examination, frozen drying 35 hours, capping gets final product.
Sublimation drying method of this process using, in pharmaceutical freeze dryers, with the goods solution of anticipating in hothouse precooling to-45 ℃, the cold preservation indoor temperature is dropped to-50 ℃ simultaneously, start vacuum pump, after treating that vacuum reaches below the 10mmHg, slowly open valve, close fridge below the 0.1mmHg when vacuum in the hothouse reaches, slowly heat, treat the water evaporates ashes to-20 ℃, slowly heat up, stable according to 40 ℃ of experiment preparation of ethylenediamine diaceturate for injection, therefore change drying again, whole dry run 35 hours at 40 ℃.
The quality standard control method:
Preparation of ethylenediamine diaceturate for injection is the aseptic freeze-dried product of diacetyl nitrilo acetic acid ethylenediamine.Contain diacetyl nitrilo acetic acid ethylenediamine (C
10H
22N
4O
6) should be 90.0%～110.0% of labelled amount.
[character] preparation of ethylenediamine diaceturate for injection is the loose block or the powder of white or off-white color.
Preparation of ethylenediamine diaceturate for injection an amount of (being equivalent to diacetyl nitrilo acetic acid ethylenediamine 10mg approximately) is got in [discriminating] (1), add 1 of potassium iodide test solution and 4% potassium iodate solution 0.5ml, put in the water-bath and heated 1 minute, cooling, add 1～4 of starch indicator solution, it is blue that solution shows.
(2) get preparation of ethylenediamine diaceturate for injection an amount of (being equivalent to diacetyl nitrilo acetic acid ethylenediamine 10mg approximately), add saturated propylene glycol salt manufacturing acid azanol 1ml, little fiery heated and boiled 3 minutes adds 1 of ferric chloride test solution after the cooling, and solution shows brownish red.
(3) get preparation of ethylenediamine diaceturate for injection an amount of (being equivalent to diacetyl nitrilo acetic acid ethylenediamine 10mg approximately), added the ninhydrin solution heated and boiled 2 minutes, it is brown that solution shows.
Clarity of [inspection] solution and color are got 5 bottles of preparation of ethylenediamine diaceturate for injection, and after the water 2ml dissolving, solution should be clarified respectively; As showing muddy, compare with No. 1 turbidity standard (two appendix IX of Chinese Pharmacopoeia version in 2000 B), all must not be denseer; As colour developing, compare with yellow or No. 2 standard color solutions of yellow green (two appendix IX of Chinese Pharmacopoeia version in 2000 A, first method), all must not be darker.
Loss on drying is got preparation of ethylenediamine diaceturate for injection, is dried to constant weight at 105 ℃, subtracts weight loss and must not cross 5.0% (Chinese Pharmacopoeia version appendix in 2000 VIII L).
It is an amount of that acidity is got preparation of ethylenediamine diaceturate for injection, adds water and make the solution that contains 0.1g among every 1ml, measures (two appendix VI of Chinese Pharmacopoeia version in 2000 H) in accordance with the law, and pH value should be 5.0～6.5.
The aseptic preparation of ethylenediamine diaceturate for injection of getting adds aquesterilisa 2ml dissolving respectively, checks (Chinese Pharmacopoeia version appendix in 2000 XI H) in accordance with the law, should be up to specification.
Bacterial endotoxin is got preparation of ethylenediamine diaceturate for injection, checks (two appendix XI of Chinese Pharmacopoeia version in 2000 E) in accordance with the law, and containing the endotoxin amount among every 1mg should be less than 0.125EU.
Other should meet every regulation relevant under the injection item (Chinese Pharmacopoeia version appendix in 2000 I B).
[assay] precision is measured preparation of ethylenediamine diaceturate for injection an amount of (being equivalent to diacetyl nitrilo acetic acid ethylenediamine 0.2g approximately), after adding water 2ml dissolving, add the thymolphthalein indicator solution is shown neutral pyridine 20ml, add thymolphthalein indicator solution number droplet, with sodium hydroxide volumetric solution (0.1mol/L) titration.Every 1ml sodium hydroxide volumetric solution (0.1mol/L) is equivalent to the C of 14.72mg
10H
22N
4O
6
[classification] hemorrhage.
[specification] 0.2g
[storage] shading, airtight, preserve in the cool.
[effect duration] tentative 2 years.
Claims (1)
1. the preparation method of preparation of ethylenediamine diaceturate for injection is characterized in that:
1), prescription
Diacetyl nitrilo acetic acid ethylenediamine 200g presses C
10H
22N
4O
6100%
Water for injection 2000ml;
2), preparation
Take by weighing diacetyl nitrilo acetic acid ethylenediamine 200g, to sterile chamber, add injection water 1000ml, stirring and dissolving adds the 0.5g active carbon, stirs 30 minutes, with 0.45 μ m microporous filter membrane device filtering decarbonization, add water for injection to 2000ml, 0.22 μ m microporous filter membrane device of reuse sterilization filters, and packing promptly gets and injects liquor after the filtrate passed examination; The filtrate frozen drying is adopted a sublimation drying method, with goods solution precooling in hothouse of anticipating, the pre-freeze temperature is-40 ℃, the pre-freeze time is 5 hours, the cold preservation indoor temperature is dropped to-50 ℃ simultaneously, starts vacuum pump, after treating that vacuum reaches below the 10mmHg, slowly open valve, close fridge below the 0.1mmHg, slowly heat to-20 ℃ when vacuum in the hothouse reaches, kept this temperature 25 hours, treat the water evaporates ashes, water content is reduced to below 8%, slowly heats up, change over to drier at 40 ℃, be 5 hours drying time again, and total time spent of whole dry run is 35 hours, promptly gets lyophilized formulations.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200510039248XA CN100418518C (en) | 2005-05-08 | 2005-05-08 | Injectable diacetylamino acetic ethylenediamine prepn. preparing method and quality-control tech. therefor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200510039248XA CN100418518C (en) | 2005-05-08 | 2005-05-08 | Injectable diacetylamino acetic ethylenediamine prepn. preparing method and quality-control tech. therefor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1723885A CN1723885A (en) | 2006-01-25 |
| CN100418518C true CN100418518C (en) | 2008-09-17 |
Family
ID=35923600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB200510039248XA Expired - Fee Related CN100418518C (en) | 2005-05-08 | 2005-05-08 | Injectable diacetylamino acetic ethylenediamine prepn. preparing method and quality-control tech. therefor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100418518C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102488663B (en) * | 2011-12-19 | 2013-08-14 | 王保明 | Drug combination containing ethylenediamine diaceturate and preparing method thereof |
| CN104352450A (en) * | 2014-10-09 | 2015-02-18 | 海南通用康力制药有限公司 | Ethylenediamine diaceturate freeze-dried powder for injection and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1422615A (en) * | 2002-12-03 | 2003-06-11 | 陈义忠 | Diacetylamino-acetoxy-ethylenediamine larg-volume injecta and preparation method thereof |
| CN1439365A (en) * | 2003-03-21 | 2003-09-03 | 于航 | Diacetyl amide acetate ethylenediamide freeze dried powder injection, large volume injection and their preparing method |
| CN1444933A (en) * | 2003-04-18 | 2003-10-01 | 张嵩 | Ethylenediamine Diaceturate injection |
| CN1454590A (en) * | 2003-05-26 | 2003-11-12 | 王景成 | Ethylenediamine diaceturate lyophilized powder injection and preparing method thereof |
| CN1541647A (en) * | 2003-11-06 | 2004-11-03 | 武汉佑德医药科技有限公司 | Di-acetyl-aminoethyl-ethylenediamine powder injection and its preparation method |
-
2005
- 2005-05-08 CN CNB200510039248XA patent/CN100418518C/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1422615A (en) * | 2002-12-03 | 2003-06-11 | 陈义忠 | Diacetylamino-acetoxy-ethylenediamine larg-volume injecta and preparation method thereof |
| CN1439365A (en) * | 2003-03-21 | 2003-09-03 | 于航 | Diacetyl amide acetate ethylenediamide freeze dried powder injection, large volume injection and their preparing method |
| CN1444933A (en) * | 2003-04-18 | 2003-10-01 | 张嵩 | Ethylenediamine Diaceturate injection |
| CN1454590A (en) * | 2003-05-26 | 2003-11-12 | 王景成 | Ethylenediamine diaceturate lyophilized powder injection and preparing method thereof |
| CN1541647A (en) * | 2003-11-06 | 2004-11-03 | 武汉佑德医药科技有限公司 | Di-acetyl-aminoethyl-ethylenediamine powder injection and its preparation method |
Non-Patent Citations (4)
| Title |
|---|
| 新凝灵注射液对颅脑手术患者凝血功能的影响. 于金铃等.齐齐哈尔医学院学报，第24卷第4期. 2003 |
| 新凝灵注射液对颅脑手术患者凝血功能的影响. 于金铃等.齐齐哈尔医学院学报，第24卷第4期. 2003 * |
| 现代药物学. 芮耀诚，第660页，人民军医出版社. 1999 |
| 现代药物学. 芮耀诚，第660页，人民军医出版社. 1999 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1723885A (en) | 2006-01-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Schreiber | The beginning of the end for damage control surgery | |
| CN108785259A (en) | A kind of pharmaceutical composition and preparation method thereof containing esomeprazole sodium | |
| CN103462911B (en) | Preparation technique of freeze-dried powder injection | |
| CN105078906A (en) | Urokinase-containing pharmaceutical lyophilized preparation and preparation method thereof | |
| CN100418518C (en) | Injectable diacetylamino acetic ethylenediamine prepn. preparing method and quality-control tech. therefor | |
| CN100496463C (en) | Omeprazole sodium freeze-dried powder injection and preparing method thereof | |
| CN102813908A (en) | Lyophilization technology for preparing bivalirudin for injection | |
| CN102836171A (en) | Solution for surgery and endoscope washing and preparation method thereof | |
| CN111904936B (en) | Famotidine freeze-dried powder injection | |
| CN105640899A (en) | Tedizolid pharmaceutical composition for injection | |
| CN106963729A (en) | It is a kind of to be used to prevent pharmaceutical preparation of operative hemorrhage and preparation method thereof | |
| CN108553413B (en) | Esomeprazole sodium for injection | |
| CN101810588A (en) | Pantoprazole sodium freeze-drying medicinal composition for injection and preparation method thereof | |
| CN103768028A (en) | Esomeprazole sodium sterile lyophilized powder for injection and preparation process of lyophilized powder | |
| CN102488663A (en) | Drug combination containing ethylenediamine diaceturate and preparing method thereof | |
| CN101143144A (en) | Milrinone lactate freezing-dried powder injection and preparation method thereof | |
| CN102988311A (en) | Thrombolytic freeze-dried powder injection and preparation method thereof | |
| CN110772487B (en) | Freeze-drying method of ethylenediamine diaceturate | |
| CN107669622B (en) | Bivalirudin injection and preparation method thereof | |
| CN105030702B (en) | One kind sodium pharmaceutical composition containing heparin and preparation method thereof | |
| CN113041226B (en) | Preparation process of pantoprazole sodium for injection | |
| CN112137969A (en) | Enoxaparin sodium for injection containing enoxaparin sodium and preparation method thereof | |
| CN103932981A (en) | Heparin sodium tube-sealing injection | |
| CN105079015A (en) | Troxerutin freeze-dried powder injection and preparation method thereof | |
| CN114159396A (en) | Espressol omeprazole sodium freeze-dried preparation for injection and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Hainan Wekon Pharmaceutical (Qianshan) Co., Ltd. Assignor: Yu Shichun Contract fulfillment period: 2008.9.19 to 2024.5.7 contract change Contract record no.: 2009340000287 Denomination of invention: Injectable diacetylamino acetic ethylenediamine prepn. preparing method and quality-control tech. therefor Granted publication date: 20080917 License type: Exclusive license Record date: 2009.9.8 |
|
| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2008.9.19 TO 2024.5.7; CHANGE OF CONTRACT Name of requester: HAINAN WEIKANG PHARMACY( QIANSHAN ) CO., LTD. Effective date: 20090908 |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080917 Termination date: 20170508 |