CN1444933A - Ethylenediamine Diaceturate injection - Google Patents
Ethylenediamine Diaceturate injection Download PDFInfo
- Publication number
- CN1444933A CN1444933A CN 03118980 CN03118980A CN1444933A CN 1444933 A CN1444933 A CN 1444933A CN 03118980 CN03118980 CN 03118980 CN 03118980 A CN03118980 A CN 03118980A CN 1444933 A CN1444933 A CN 1444933A
- Authority
- CN
- China
- Prior art keywords
- injection
- acetic acid
- acid ethylenediamine
- nitrilo acetic
- diacetyl nitrilo
- 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
- 239000007924 injection Substances 0.000 title claims abstract description 54
- 238000002347 injection Methods 0.000 title claims abstract description 54
- GKNAKQZZLBLSLI-UHFFFAOYSA-N 2-acetamidoacetic acid;ethane-1,2-diamine Chemical compound NCCN.CC(=O)NCC(O)=O.CC(=O)NCC(O)=O GKNAKQZZLBLSLI-UHFFFAOYSA-N 0.000 title abstract description 11
- 238000001802 infusion Methods 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 4
- -1 diacetyl nitrilo acetic acid ethylenediamine Chemical compound 0.000 claims description 66
- 239000007788 liquid Substances 0.000 claims description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 17
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000007951 isotonicity adjuster Substances 0.000 claims description 11
- 239000008103 glucose Substances 0.000 claims description 10
- 235000001727 glucose Nutrition 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000008215 water for injection Substances 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 229920002307 Dextran Polymers 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 238000007689 inspection Methods 0.000 claims description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 4
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 4
- 239000011780 sodium chloride Substances 0.000 claims description 4
- 235000002639 sodium chloride Nutrition 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 235000010356 sorbitol Nutrition 0.000 claims description 4
- 239000000811 xylitol Substances 0.000 claims description 4
- 235000010447 xylitol Nutrition 0.000 claims description 4
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 4
- 229960002675 xylitol Drugs 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000005262 decarbonization Methods 0.000 claims description 3
- 238000009413 insulation Methods 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 239000012982 microporous membrane Substances 0.000 claims description 3
- 238000009287 sand filtration Methods 0.000 claims description 3
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- 235000011148 calcium chloride Nutrition 0.000 claims description 2
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 2
- 235000011147 magnesium chloride Nutrition 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- 239000001540 sodium lactate Substances 0.000 claims description 2
- 235000011088 sodium lactate Nutrition 0.000 claims description 2
- 229940005581 sodium lactate Drugs 0.000 claims description 2
- 239000006184 cosolvent Substances 0.000 claims 1
- 239000003978 infusion fluid Substances 0.000 abstract description 6
- 238000001990 intravenous administration Methods 0.000 abstract description 6
- 206010011409 Cross infection Diseases 0.000 abstract description 2
- 206010029803 Nosocomial infection Diseases 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000004480 active ingredient Substances 0.000 abstract 1
- 238000003113 dilution method Methods 0.000 abstract 1
- 229940090044 injection Drugs 0.000 description 41
- 238000012360 testing method Methods 0.000 description 30
- 238000000034 method Methods 0.000 description 11
- 208000032843 Hemorrhage Diseases 0.000 description 9
- 239000002994 raw material Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 206010002198 Anaphylactic reaction Diseases 0.000 description 5
- 241000700199 Cavia porcellus Species 0.000 description 5
- 206010020565 Hyperaemia Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 230000036783 anaphylactic response Effects 0.000 description 5
- 208000003455 anaphylaxis Diseases 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229940093181 glucose injection Drugs 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 206010018910 Haemolysis Diseases 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000002949 hemolytic effect Effects 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 3
- 102000002322 Egg Proteins Human genes 0.000 description 3
- 108010000912 Egg Proteins Proteins 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 208000005392 Spasm Diseases 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000008588 hemolysis Effects 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 210000004681 ovum Anatomy 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 240000007711 Peperomia pellucida Species 0.000 description 2
- 208000034158 bleeding Diseases 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000002932 luster Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 240000006409 Acacia auriculiformis Species 0.000 description 1
- 206010001742 Allergy to animal Diseases 0.000 description 1
- 235000017166 Bambusa arundinacea Nutrition 0.000 description 1
- 235000017491 Bambusa tulda Nutrition 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 108010088842 Fibrinolysin Proteins 0.000 description 1
- 206010048865 Hypoacusis Diseases 0.000 description 1
- 102000004317 Lyases Human genes 0.000 description 1
- 108090000856 Lyases Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 244000082204 Phyllostachys viridis Species 0.000 description 1
- 235000015334 Phyllostachys viridis Nutrition 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010038727 Respiratory tract haemorrhage Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000011425 bamboo Substances 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- UCDKONUHZNTQPY-UHFFFAOYSA-N bromhexine hydrochloride Chemical compound Cl.C1CCCCC1N(C)CC1=CC(Br)=CC(Br)=C1N UCDKONUHZNTQPY-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002389 essential drug Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940001501 fibrinolysin Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses an ethylenediamine diaceturate injection (i.e. ethylenediamine diaceturate infusion solution) which is composed of ethylenediamine diaceturate as an active ingredient and a medicinal carrier, wherein the ethylenediamine diaceturate and the medicinal carrier are composed of ethylenediamine diaceturate containing 0.01-6.0% of ethylenediamine diaceturate and medicinal carrier containing 99.99-94.0% of medicinal carrier (by weight) in any proportion. The ethylenediamine diaceturate injection can be suitable for large infusion solutions of various specifications. The ethylenediamine diaceturate injection can be directly used for intravenous infusion, eliminates the dilution process in the existing medication situation, avoids cross infection, improves the clinical application level and safety of ethylenediamine diaceturate, and is convenient for patients to use.
Description
Technical field
The present invention relates to a kind of injection, especially a kind of diacetyl nitrilo acetic acid ethylenediamine injection.
Background technology
Diacetyl nitrilo acetic acid ethylenediamine is the hemorrhage that China develops voluntarily, original name: ethylenediamine diaceturate.Have the former activator of lyase, plasminogen can not be activated be fibrinolysin, thereby suppress fibrinous dissolving; Promote the platelet release of active agent, strengthen hematoblastic aggregation and adhesiveness, shorten clotting time; Strengthen capillary resistance, reduce the permeability of blood capillary.Be applicable to that prevention and treatment a variety of causes are hemorrhage., respiratory tract hemorrhage hemorrhage to operation oozing of blood, surgery, face are hemorrhage, gynecological bleeding, bleeding hemorrhoids, urinary tract is hemorrhage, cancer is hemorrhage, digestive tract hemorrhage, cranium cerebral hemorrhage etc. all have better curative effect.
Diacetyl nitrilo acetic acid ethylenediamine raw material and injection record in first of National Drug Administration's " national drug standards ".Belong to national essential drugs.The existing market supply mainly have only aqueous injection, dosage form is more single, muscle or intravenous injection are used with glucose injection dilution back during intravenous injection.Because the liquid of getting before the intravenous injection mixes, and has brought some shortcomings, not only formality is loaded down with trivial details, and be subjected to the pollution of environment, apparatus easily, user produces infusion reaction, as have a fever, feel sick, feel cold, tachycardia or slow excessively etc., can jeopardize patient's life in the time of seriously.
Summary of the invention
The objective of the invention is to overcome above-mentioned shortcoming, the joint product of development diacetyl nitrilo acetic acid ethylenediamine and infusion solutions.
Technical scheme of the present invention is: a kind of diacetyl nitrilo acetic acid ethylenediamine injection (being diacetyl nitrilo acetic acid ethylenediamine infusion solutions) is made up of diacetyl nitrilo acetic acid ethylenediamine and pharmaceutical carrier as active component, and wherein diacetyl nitrilo acetic acid ethylenediamine and pharmaceutical carrier are formed with diacetyl nitrilo acetic acid ethylenediamine that contains 0.01-6.0% and the arbitrary proportion that contains 99.99-94.0% pharmaceutical carrier (weight).Pharmaceutical carrier in the diacetyl nitrilo acetic acid ethylenediamine injection of the present invention has isotonic agent such as sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol or dextran (dextran that comprises big or middle or small-molecular weight) etc.; Buffer agent example hydrochloric acid, acetic acid, lactic acid or sodium hydroxide etc. also have water for injection.Can not contain or contain simultaneously one or more isotonic agents in the diacetyl nitrilo acetic acid ethylenediamine injection of the present invention.
The preparation method of diacetyl nitrilo acetic acid ethylenediamine injection of the present invention comprises the following steps: (1) preparation isotonic agent concentrated wiring liquid: get the water for injection that isotonic agent adds 3 times of amounts, stirring and dissolving, add 0.3% active carbon and boiled 30 minutes,, get concentrated wiring liquid through sand filtration rod filtering decarbonization.(2) preparation diacetyl nitrilo acetic acid ethylenediamine concentrated wiring liquid: it is an amount of to get water for injection, adds diacetyl nitrilo acetic acid ethylenediamine, stirs and makes dissolving, gets diacetyl nitrilo acetic acid ethylenediamine concentrated wiring liquid.(3) preparation diacetyl nitrilo acetic acid ethylenediamine injection: get above-mentioned isotonic agent concentrated wiring liquid and diacetyl nitrilo acetic acid ethylenediamine concentrated wiring liquid and merge, add to the full amount of water for injection again, add 0.02% active carbon, stir evenly, insulation was placed 30 minutes, filter, measure intermediate content and pH value, qualified after 0.45 μ m filtering with microporous membrane, fill is in infusion bottle, through the routine sterilization, lamp inspection makes diacetyl nitrilo acetic acid ethylenediamine injection after the quality inspection.
The invention has the advantages that: diacetyl nitrilo acetic acid ethylenediamine injection of the present invention is applicable to the infusion solutions of all size.Diacetyl nitrilo acetic acid ethylenediamine injection of the present invention can be directly used in venoclysis, has reduced the dilution in the existing medicining condition, avoids cross infection, and improves the clinical practice level and the safety of diacetyl nitrilo acetic acid ethylenediamine, also is convenient to patient and uses.
The survey report that is used for the diacetyl nitrilo acetic acid ethylenediamine injection that method of the present invention makes is as follows: the name of an article: diacetyl nitrilo acetic acid ethylenediamine injection character: this product is that colourless or almost colourless clear liquid is differentiated: be the positive reaction pH value: 5.0-7.0 diacetyl nitrilo acetic acid ethylenediamine content is labelled amount %:90-110% related substance:＜1.0% other: meet and require sterility test under the injection item: qualified pyrogen testing: qualified
Bisolvon injection hemolytic test report of the present invention is as follows: sample: diacetyl nitrilo acetic acid ethylenediamine injection prepares unit: open high detection unit: pharmacology teaching and research room of Jiangxi Medical College one, test objective:
When investigating the intravenous drip of diacetyl nitrilo acetic acid ethylenediamine injection, whether cause the body hemolytic reaction.Two, animal:
Experimental rabbit, body weight 2.2kg, Jiangxi Province's medical experiment animal center provides, the quality certification number: 021-9703 three, method:
Get 1 of experimental rabbit, from the about 10ml of heart extracting blood, put in the beaker, stir with bamboo let and remove fibrin, then blood is moved in the graduated centrifuge tube, add normal saline 5-10ml, behind the mixing centrifugal 5 minutes (2000-2500r/ branch), remove supernatant, it is centrifugal to add the normal saline mixing again, wash 3-4 time repeatedly, be water white transparency to supernatant and can be used for test.The gained erythrocyte is diluted to 2% suspension with normal saline, standby.
Get 7 in test tube, numbering is arranged on the test tube rack, add 2% red cell suspension and normal saline successively by table 1 proportional quantity, each pipe is shaken up gently, behind the mixing, in 37 ℃ of calorstats, place half an hour, 1～No. 5 pipe adds not commensurability test sample respectively, and the 6th pipe only adds normal saline and makes blank usefulness, and the 7th only manages adding distil water makes positive control, behind the mixing, put in 37 ℃ of calorstats.Beginning was observed once every 15 minutes, observed once every 1 hour after 1 hour.Observed 4 hours, and observed solution and haemolysis or coacervation whether occur.Four, result:
Test sample diacetyl nitrilo acetic acid ethylenediamine injection hemolytic test feminine gender.
The table test sample is to erythrocytic influence
Annotate: "+" expression haemolysis; Haemolysis and red blood cell condensation do not appear in "-" expression.Five, conclusion:
Above results suggest: test sample hemolytic test feminine gender, so can think that diacetyl nitrilo acetic acid ethylenediamine injection hemolytic test is qualified.
Diacetyl nitrilo acetic acid ethylenediamine injection sensitivity test of the present invention is reported as follows: sample: diacetyl nitrilo acetic acid ethylenediamine injection prepares unit: open high detection unit: pharmacology teaching and research room of Jiangxi Medical College one, test objective:
When investigating the intravenous drip of diacetyl nitrilo acetic acid ethylenediamine injection, whether can cause the body anaphylaxis.Two, animal:
Healthy guinea pig, male and female half and half, body weight 250-300g, emerging HUAMU animal shop, Shanghai, the quality certification number: 02-05-4 three, method
Get 16 of healthy guinea pigs, be divided into 2 groups at random, A at the 1st, 3,5 day lumbar injection test sample 0.5ml/ only organizes, and the B group lumbar injection 5% fresh Ovum Gallus domesticus album normal saline solution 0.5ml/ same period only makes animal allergy.A, B are divided into 2 groups respectively for two groups more then, and A1 organizes in injecting back 14 days first, and 2ml/ only attacks observation by the intravenous injection test sample, and the A2 group is then injected in first and attacked with method in back 21 days.B1,2 groups also only attack respectively at corresponding intravenous injection in period 5% fresh Ovum Gallus domesticus album normal saline solution 2ml/, and close observation injection back animal has or not anaphylaxiss such as grabbing nose, perpendicular hair, dyspnea, spasm, shock, death.Four, result
Test sample diacetyl nitrilo acetic acid ethylenediamine injection does not have obvious anaphylaxis to Cavia porcellus, and positive reference substance 5% fresh Ovum Gallus domesticus album normal saline solution then causes the Cavia porcellus severe allergic reaction.
The table test sample is counted 14 days irritated the 21st day allergy of priming dose aggressive agent flow control to the anaphylaxis group Mus of Cavia porcellus
(only) order of reaction order of reaction test sample 8 0.5ml/ 2ml/ is 0 grade 0 grade 5% new fresh hen egg 8 a 0.5ml/ 2ml/ 4 grades 4 grades clear normal saline solution five, conclusion only
Above results suggest, test sample fails to cause obvious anaphylaxis to Cavia porcellus, so can think that diacetyl nitrilo acetic acid ethylenediamine injection hypersensitive test is qualified.
Diacetyl nitrilo acetic acid ethylenediamine injection local irritation test report of the present invention is as follows: sample: diacetyl nitrilo acetic acid ethylenediamine injection prepares unit: open high detection unit: pharmacology teaching and research room of Jiangxi Medical College one, test objective:
When investigating the intravenous drip of diacetyl nitrilo acetic acid ethylenediamine glucose injection, whether can cause blood vessel irritation.Two, animal:
Experimental rabbit, male and female half and half, body weight 2.0-2.5kg, Jiangxi Province's medical experiment animal center provides, the quality certification number: 021-9703 three, test method
Get 6 of healthy experimental rabbits, fix 1 hour after, at its left auricular vein with a certain amount of test sample of 4# scalp acupuncture intravenous drip (by the conversion of clinical application amount, 1ml/ branch), for three days on end, every day 1 time; Auris dextra gives equivalent 5% glucose injection with same procedure.The close observation vein has or not expansion, spasm and part to have or not phenomenons such as hyperemia, edema.Observing venous simultaneously, hard of hearing corresponding site does not have or insufficiency of blood pipe place difference subcutaneous injection test sample and normal saline solution in the left and right sides, and diameter about 0.5cm in skin mound observes the skin mound and has or not hyperemia, edema and extinction time.After last administration finishes, cut one section away from the about 2cm in needle point the place ahead place blood vessel rapidly, fix with 10% formalin be, conventional embedding, stained, microscopically is observed and is had or not pathological change.Four, result
Perusal Pi Qiu position: skin mound, the corresponding position of left and right sides ear does not all have abnormal changes such as obvious hyperemia, edema; In the intravenous drip process, venectasia, spasm and hyperemia, edema phenomenon all do not appear in each rabbit administration and contrast ear; The pathology microscopy shows: the blood vessel wall structure is clear, and no expansion, hyperemia and erythrocyte spill phenomenon.Five, conclusion
Above results suggest, test sample does not have obvious irritation to rabbit ear edge vein blood vessel and rabbit ear subcutaneous tissue, so can think that the local excitation of diacetyl nitrilo acetic acid ethylenediamine injection is up to specification.Diacetyl nitrilo acetic acid ethylenediamine injection study on the stability:
According to the requirement of two appendix XIXC of Chinese Pharmacopoeia version in 2000 medicine stability test guideline, infusion solutions quality stability is investigated through 40 ℃ of 6 months (being equivalent to room temperature 2 years) of acceleration and 6 months study on the stability of long-term stable experiment, and the result is as follows:
40 ℃ are quickened six months results:
| Sample number | Time (moon) | Content (%) | PH value | Clarity | Color and luster | |
| Diacetyl nitrilo acetic acid ethylenediamine | Sodium chloride | |||||
| ????1 | ????0 | ????102.8 | ????101.2 | ????5.8 | Up to specification | Up to specification |
| ????1 | ????103.0 | ????101.2 | ????5.9 | Up to specification | Up to specification | |
| ????2 | ????102.3 | ????101.4 | ????5.8 | Up to specification | Up to specification | |
| ????3 | ????101.7 | ????100.9 | ????5.7 | Up to specification | Up to specification | |
| ????6 | ????101.1 | ????101.3 | ????5.8 | Up to specification | Up to specification | |
| ????2 | ????0 | ????101.9 | ????100.5 | ????6.0 | Up to specification | Up to specification |
| ????1 | ????101.8 | ????100.9 | ????6.1 | Up to specification | Up to specification | |
| ????2 | ????101.1 | ????101.1 | ????5.9 | Up to specification | Up to specification | |
| ????3 | ????101.4 | ????100.7 | ????6.0 | Up to specification | Up to specification | |
| ????6 | ????101.3 | ????100.7 | ????6.0 | Up to specification | Up to specification | |
| ????3 | ????0 | ????100.8 | ????99.9 | ????5.5 | Up to specification | Up to specification |
| ????1 | ????100.6 | ????100.0 | ????5.7 | Up to specification | Up to specification | |
| ????2 | ????100.9 | ????100.4 | ????5.5 | Up to specification | Up to specification | |
| ????3 | ????100.5 | ????99.7 | ????5.6 | Up to specification | Up to specification | |
| ????6 | ????99.9 | ????100.2 | ????5.5 | Up to specification | Up to specification | |
6 months results of long term test:
| Sample number | Time (moon) | Content (%) | PH value | Clarity | Color and luster | |
| Diacetyl nitrilo acetic acid ethylenediamine | Sodium chloride | |||||
| ????1 | ????0 | ????102.8 | ????101.2 | ????5.8 | Up to specification | Up to specification |
| ????3 | ????101.7 | ????101.3 | ????5.8 | Up to specification | Up to specification | |
| ????6 | ????102.1 | ????101.3 | ????5.9 | Up to specification | Up to specification | |
| ????0 | ????101.9 | ????100.5 | ????6.0 | Up to specification | Up to specification | |
| ????2 | ????3 | ????101.2 | ????100.8 | ????6.1 | Up to specification | Up to specification |
| ????6 | ????100.6 | ????100.8 | ????6.0 | Up to specification | Up to specification | |
| ????3 | ????0 | ????100.8 | ????99.9 | ????5.5 | Up to specification | Up to specification |
| ????3 | ????101.4 | ????100.4 | ????5.6 | Up to specification | Up to specification | |
| ????6 | ????100.0 | ????100.2 | ????5.6 | Up to specification | Up to specification |
Conclusion: six months by a definite date accelerated test and long-term stable experiment explanation this product preliminarily stabilised is better, steady quality in this product room temperature 2 years.
Specific embodiment example 1: preparation glucose concentrated wiring liquid
Get glucose for injection 5000g, add injection water 15000ml, stirring and dissolving adds the 45g active carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, gets concentrated wiring liquid.Example 2: preparation diacetyl nitrilo acetic acid ethylenediamine concentrated wiring liquid
It is an amount of to get water for injection, adds diacetyl nitrilo acetic acid ethylenediamine 600g, stirs and makes dissolving, gets diacetyl nitrilo acetic acid ethylenediamine concentrated wiring liquid.Example 3: preparation diacetyl nitrilo acetic acid ethylenediamine glucose injection
Treating excess syndrome example 1 glucose concentrated wiring liquid and example 2 diacetyl nitrilo acetic acid ethylenediamine concentrated wiring liquids merge, add the injection water again to 100000ml, add the 20g active carbon, stir evenly, insulation was placed 30 minutes, filter, regulate pH value 5.0-7.0 with 0.1mol/LHCl and 0.1mol/L NaOH, measure intermediate content, qualified after 0.45 μ m filtering with microporous membrane, fill are in infusion bottle or transfusion bag, through 115 ℃ of pressure sterilizings 30 minutes, cooling back lamp inspection promptly gets diacetyl nitrilo acetic acid ethylenediamine glucose injection after the product inspection.Example 4: preparation contains the diacetyl nitrilo acetic acid ethylenediamine injection of sorbitol
Press the method for example 1-3, replace glucose to make as raw material with sorbitol.Example 5: preparation contains the diacetyl nitrilo acetic acid ethylenediamine injection of xylitol
Press the method for example 1-3, replace glucose to make as raw material with xylitol.Example 6: preparation contains the diacetyl nitrilo acetic acid ethylenediamine injection of dextran (comprising big or middle or small-molecular weight dextran)
Press the method for example 1-3, replace glucose to make as raw material with dextran.Example 7: the diacetyl nitrilo acetic acid ethylenediamine injection of preparation sodium chloride-containing
Press the method for example 1-3, replace glucose to make as raw material with sodium chloride.Example 8: preparation contains the diacetyl nitrilo acetic acid ethylenediamine injection of mannitol
Press the method for example 1-3, replace glucose to make as raw material with mannitol.
Claims (5)
1, a kind of diacetyl nitrilo acetic acid ethylenediamine injection, it is characterized in that this medicine diacetyl nitrilo acetic acid ethylenediamine injection is made up of as active component and pharmaceutical carrier diacetyl nitrilo acetic acid ethylenediamine, it can contain the diacetyl nitrilo acetic acid ethylenediamine of 0.01-6.0% by weight percentage and form with arbitrary proportion with the pharmaceutical carrier that contains 99.99-94.0%.
2, diacetyl nitrilo acetic acid ethylenediamine injection according to claim 1 is characterized in that wherein said pharmaceutical carrier has isotonic agent, buffer agent, cosolvent and water for injection.
3, according to claim 1 and 2 described diacetyl nitrilo acetic acid ethylenediamine injection, it is characterized in that wherein used isotonic agent can be sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, mannitol, sorbitol or dextran.
4, according to claim 1 and 2 described diacetyl nitrilo acetic acid ethylenediamine injection, it is characterized in that not contain or to contain simultaneously multiple isotonic agent in this injection.
5, a kind of preparation method as claim 1 and described diacetyl nitrilo acetic acid ethylenediamine injection is characterized in that this preparation method comprises the following steps:
(1) preparation isotonic agent concentrated wiring liquid
Get the water for injection that isotonic agent adds 3 times of amounts, stirring and dissolving adds 0.3% active carbon and boiled 30 minutes, through sand filtration rod filtering decarbonization, gets concentrated wiring liquid.
(2) preparation diacetyl nitrilo acetic acid ethylenediamine concentrated wiring liquid
It is an amount of to get water for injection, adds diacetyl nitrilo acetic acid ethylenediamine, stirs and makes dissolving, gets diacetyl nitrilo acetic acid ethylenediamine concentrated wiring liquid.
(3) preparation diacetyl nitrilo acetic acid ethylenediamine injection is got above-mentioned isotonic agent concentrated wiring liquid and the merging of diacetyl nitrilo acetic acid ethylenediamine concentrated wiring liquid, adds to the full amount of water for injection again, adds 0.02% active carbon, stir evenly, insulation was placed 30 minutes, filtered, and measured intermediate content, regulate pH value 5.0-7.0 with 10% sodium hydroxide, through 0.45 μ m filtering with microporous membrane, fill is sterilized through routine in infusion bottle or transfusion bag, lamp inspection makes diacetyl nitrilo acetic acid ethylenediamine injection after the quality inspection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03118980 CN1444933A (en) | 2003-04-18 | 2003-04-18 | Ethylenediamine Diaceturate injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03118980 CN1444933A (en) | 2003-04-18 | 2003-04-18 | Ethylenediamine Diaceturate injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1444933A true CN1444933A (en) | 2003-10-01 |
Family
ID=27814995
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03118980 Pending CN1444933A (en) | 2003-04-18 | 2003-04-18 | Ethylenediamine Diaceturate injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1444933A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100418518C (en) * | 2005-05-08 | 2008-09-17 | 余世春 | Injectable diacetylamino acetic ethylenediamine prepn. preparing method and quality-control tech. therefor |
| CN102367229A (en) * | 2011-08-19 | 2012-03-07 | 江西新先锋医药有限公司 | Ethylenediamine diaceturate compound and pharmaceutical composition thereof |
-
2003
- 2003-04-18 CN CN 03118980 patent/CN1444933A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100418518C (en) * | 2005-05-08 | 2008-09-17 | 余世春 | Injectable diacetylamino acetic ethylenediamine prepn. preparing method and quality-control tech. therefor |
| CN102367229A (en) * | 2011-08-19 | 2012-03-07 | 江西新先锋医药有限公司 | Ethylenediamine diaceturate compound and pharmaceutical composition thereof |
| CN102367229B (en) * | 2011-08-19 | 2012-08-29 | 江西新先锋医药有限公司 | Ethylenediamine diaceturate compound and pharmaceutical composition thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101785754A (en) | Intravenous drug delivery system for ibuprofen and preparation method thereof | |
| CN102018675B (en) | Carbazochrome sodium sulfonate freeze-dried powder injection and preparation method thereof | |
| CN1184963C (en) | Bromhexine hydrochloride injection and its preparation method | |
| CN1759832A (en) | Carbazochrome sodium sulfonate for injection, and preparation method | |
| CN1444931A (en) | Aceglutamide injection | |
| CN1444933A (en) | Ethylenediamine Diaceturate injection | |
| CN105311622B (en) | A kind of combination medicine that treating pain and its preparation, preparation method | |
| Lorber et al. | Entero-Hepatic Circulation of Bromsulphalein: I. Studies on Man with Special Reference to the Clinical BSP Test | |
| CN111265477B (en) | Carbazochrome sodium sulfonate and sodium chloride injection and preparation method thereof | |
| Najari et al. | Compatibility of commonly used bone marrow transplant drugs during Y-site delivery | |
| CN1559417A (en) | Gastrodin venous injection liquid, and its prepn. method | |
| CN100409835C (en) | Composition and great volume injection containing bromhexine salt and the injection preparing process | |
| CN107157924A (en) | Naproxen sodium sodium chloride injection and preparation method thereof | |
| CN1200715C (en) | Adetphos sodium chloride injection and its preparation method | |
| CN102441160B (en) | Thymosin alpha1 medicinal composition and preparation method thereof | |
| Sappington | The use of heparin in blood transfusions | |
| CN116211901B (en) | Method for preparing brucea javanica oil composition and application thereof | |
| CN114522221B (en) | Application of secreted protein CTGF in preparation of medicine for treating acute lung injury | |
| CN1422615A (en) | Diacetylamino-acetoxy-ethylenediamine larg-volume injecta and preparation method thereof | |
| SATTERLEE et al. | TRANSFUSION OFBLOOD WITH SPECIAL REFERENCE TO THE USE OF ANTICOAGULANTS | |
| CN1513443A (en) | Large volume injection of lysine glucose hydrochloride, and its prepn. method | |
| CN106680470B (en) | A method of fine drug maximum tolerated dose in human body drops in measurement | |
| CN1504186A (en) | Large volume injection liquid of ethylenediamine diaceturate and its preparation method | |
| Huang et al. | Clinical efficacy of two different nursing methods in uremic patients on hemodialysis | |
| CN109984997A (en) | Formic acid injection and its application in treatment cardiovascular and cerebrovascular disease |
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 |