CN101890061A - Method for preparing ginkgo biloba leaf extract injection, and ginkgo biloba leaf extract injection - Google Patents
Method for preparing ginkgo biloba leaf extract injection, and ginkgo biloba leaf extract injection Download PDFInfo
- Publication number
- CN101890061A CN101890061A CN 201010233165 CN201010233165A CN101890061A CN 101890061 A CN101890061 A CN 101890061A CN 201010233165 CN201010233165 CN 201010233165 CN 201010233165 A CN201010233165 A CN 201010233165A CN 101890061 A CN101890061 A CN 101890061A
- Authority
- CN
- China
- Prior art keywords
- injection
- leaf extract
- ginkgo biloba
- biloba leaf
- sodium
- 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.)
- Granted
Links
- 238000002347 injection Methods 0.000 title claims abstract description 67
- 239000007924 injection Substances 0.000 title claims abstract description 67
- 229940106580 ginkgo biloba leaf extract Drugs 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims abstract description 12
- 239000000284 extract Substances 0.000 claims abstract description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000008215 water for injection Substances 0.000 claims abstract description 22
- 238000001914 filtration Methods 0.000 claims abstract description 21
- 238000003756 stirring Methods 0.000 claims abstract description 21
- 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 abstract description 6
- 229930195725 Mannitol Natural products 0.000 claims abstract description 6
- 239000000594 mannitol Substances 0.000 claims abstract description 6
- 235000010355 mannitol Nutrition 0.000 claims abstract description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 48
- 241000218628 Ginkgo Species 0.000 claims description 32
- 235000011201 Ginkgo Nutrition 0.000 claims description 32
- 235000008100 Ginkgo biloba Nutrition 0.000 claims description 32
- 244000194101 Ginkgo biloba Species 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 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 15
- 239000000600 sorbitol Substances 0.000 claims description 15
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 14
- 239000003381 stabilizer Substances 0.000 claims description 11
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 10
- 230000001954 sterilising effect Effects 0.000 claims description 9
- 238000004659 sterilization and disinfection Methods 0.000 claims description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 6
- 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 5
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 5
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 5
- 235000010265 sodium sulphite Nutrition 0.000 claims description 5
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 4
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 4
- 235000019800 disodium phosphate Nutrition 0.000 claims description 4
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 4
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 4
- 239000001488 sodium phosphate Substances 0.000 claims description 4
- 235000011008 sodium phosphates Nutrition 0.000 claims description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 4
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
- 229930003268 Vitamin C Natural products 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 235000018417 cysteine Nutrition 0.000 claims description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 3
- 229930182817 methionine Natural products 0.000 claims description 3
- 235000006109 methionine Nutrition 0.000 claims description 3
- 235000019154 vitamin C Nutrition 0.000 claims description 3
- 239000011718 vitamin C Substances 0.000 claims description 3
- 239000002120 nanofilm Substances 0.000 claims description 2
- -1 flavone glycoside Chemical class 0.000 abstract description 18
- 229930182470 glycoside Natural products 0.000 abstract description 18
- 238000002156 mixing Methods 0.000 abstract description 3
- 230000001105 regulatory effect Effects 0.000 abstract description 3
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 abstract 1
- 229930003944 flavone Natural products 0.000 abstract 1
- 235000011949 flavones Nutrition 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 53
- 239000013558 reference substance Substances 0.000 description 35
- 239000000243 solution Substances 0.000 description 32
- 230000000052 comparative effect Effects 0.000 description 25
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 24
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 22
- IYRMWMYZSQPJKC-UHFFFAOYSA-N kaempferol Chemical compound C1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 IYRMWMYZSQPJKC-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- SQGLUEWZRKIEGS-UHFFFAOYSA-N Ginkgetin Natural products C1=CC(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(OC)C(C=3C(=CC=C(C=3)C=3OC4=CC(O)=CC(O)=C4C(=O)C=3)O)=C2O1 SQGLUEWZRKIEGS-UHFFFAOYSA-N 0.000 description 13
- 229930045534 Me ester-Cyclohexaneundecanoic acid Natural products 0.000 description 13
- GQODBWLKUWYOFX-UHFFFAOYSA-N Isorhamnetin Natural products C1=C(O)C(C)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 GQODBWLKUWYOFX-UHFFFAOYSA-N 0.000 description 12
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 12
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 12
- 235000008800 isorhamnetin Nutrition 0.000 description 12
- 235000005875 quercetin Nutrition 0.000 description 12
- 229960001285 quercetin Drugs 0.000 description 12
- UBSCDKPKWHYZNX-UHFFFAOYSA-N Demethoxycapillarisin Natural products C1=CC(O)=CC=C1OC1=CC(=O)C2=C(O)C=C(O)C=C2O1 UBSCDKPKWHYZNX-UHFFFAOYSA-N 0.000 description 10
- IZQSVPBOUDKVDZ-UHFFFAOYSA-N isorhamnetin Chemical compound C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 IZQSVPBOUDKVDZ-UHFFFAOYSA-N 0.000 description 10
- 235000008777 kaempferol Nutrition 0.000 description 10
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 description 10
- 102000011759 adducin Human genes 0.000 description 6
- 108010076723 adducin Proteins 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000006166 lysate Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- SQFSKOYWJBQGKQ-UHFFFAOYSA-N kaempferide Chemical compound C1=CC(OC)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 SQFSKOYWJBQGKQ-UHFFFAOYSA-N 0.000 description 2
- 229930182487 phenolic glycoside Natural products 0.000 description 2
- 150000007950 phenolic glycosides Chemical class 0.000 description 2
- 229960000502 poloxamer Drugs 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000009429 Ginkgo biloba extract Substances 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 101100489867 Mus musculus Got2 gene Proteins 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 229930182486 flavonoid glycoside Natural products 0.000 description 1
- 150000007955 flavonoid glycosides Chemical class 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 229940068052 ginkgo biloba extract Drugs 0.000 description 1
- 235000020686 ginkgo biloba extract Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000012859 sterile filling Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000011003 system suitability test Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Images
Landscapes
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a method for preparing ginkgo biloba leaf extract injection, and ginkgo biloba leaf extract injection. The method for preparing the ginkgo biloba leaf extract injection comprises the following steps of: mixing, namely mixing a biloba leaf extract and sorbierite or mannitol; dissolving, namely adding a proper amount of 95 percent ethanol and water for injection in turn, and stirring; regulating the pH value, namely adding an alkaline pH regulator to regulate the pH value to a physiologically acceptable range; and performing aseptic filtration and filling. The ginkgo biloba leaf extract injection is prepared by the method. The content of flavone glycoside can be improved by using the same raw material.
Description
Technical field
The present invention relates to gingko leaf extract injection, the gingko leaf extract injection that particularly relates to a kind of preparing ginkgo biloba leaf extract injection and make according to this preparation method.
Background technology
Semen Ginkgo is an ancient plant, and its leaf is done medicinal in the history in existing several thousand of China.Folium Ginkgo extract is widely used in treatment brain and peripheral blood flow circulatory disturbance and malnutrition clinically, acute and chronic brain insufficiency and sequela thereof, and ear's blood flow and neurological disorder, peripheral circulation disorders etc., its main active is a total flavonoid of ginkgo.
The preparation method of existing Folium Ginkgo extract injection mainly comprises steps such as dissolving, filtration, fill.As publication number is the patent application of CN1517088A, a kind of preparation method of Folium Ginkgo extract is disclosed, comprise, at first poloxamer is dissolved in the water for injection, adds Folium Ginkgo extract then and stir, add pH value regulator (as sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium phosphate, sodium dihydrogen phosphate, sodium hydrogen phosphate etc.) solution adjust pH 5.0-7.0, cold preservation 24-72 hour, filter aseptic filtration, aseptic subpackaged sealing.In addition, as publication number is the patent application of CN1911257A, discloses a kind of preparation method of Folium Ginkgo extract, comprises, dissolving: take by weighing the 200g sorbitol and add 5% ethanol 4500m1, stirring makes dissolving fully, adds the 10g Folium Ginkgo extract, stirs to make dissolving fully, an amount of with 20%NaOH, transfer pH to be about 5.5, add 5% alcoholic solution at last, stir and make mix homogeneously to prescribed volume; Filter: respectively through 0.45 micron and 0.2 micron microporous filter membrane pressurization filtration; Fill: will filter medicinal liquid and cut open in the bottle in the peace of having handled by every 5.1-5.2ml sterile filling.In the preparation method of existing Folium Ginkgo extract injection, be Folium Ginkgo extract directly to be added solvent (solvent, as be dissolved with the water for injection of poloxamer or sorbitol) or is incorporated in the solvent dissolve, but the Folium Ginkgo extract solute effect is not satisfactory.
Summary of the invention
Because above-mentioned existing in prior technology defective the objective of the invention is to, a kind of new preparing ginkgo biloba leaf extract injection and gingko leaf extract injection thereof are provided, make it under the same materials condition, can improve the content of ginkgetin glycosides.
To achieve these goals, a kind of preparing ginkgo biloba leaf extract injection according to the present invention proposes may further comprise the steps: blend step, mix Folium Ginkgo extract with sorbitol or mannitol; Dissolving step adds 95% an amount of ethanol, water for injection stirring successively; And
The present invention also can be applied to the following technical measures to achieve further.
Aforesaid preparing ginkgo biloba leaf extract injection, the temperature of wherein said blend step is less than 30 ℃.
Aforesaid preparing ginkgo biloba leaf extract injection, the weight ratio of wherein said Folium Ginkgo extract and sorbitol or mannitol are 1: 5-6.
Aforesaid preparing ginkgo biloba leaf extract injection wherein before or after the adjust pH step, also comprises the step that adds stabilizing agent.
Aforesaid preparing ginkgo biloba leaf extract injection, wherein said stabilizing agent is selected from one or more in sodium sulfite, sodium pyrosulfite, sodium sulfite, sodium pyrosulfite, cysteine, methionine, vitamin C or the thiourea; Preferably, the consumption of described stabilizing agent is the injection volume percentage ratio of 0.05%-0.3%, more preferably 0.15%.
Aforesaid preparing ginkgo biloba leaf extract injection, wherein said dissolving step comprises: add a small amount of 95% ethanol, water for injection stirring earlier, add an amount of 95% ethanol, water for injection and 0.1mol sodium hydroxide again and stir, add injection water to recipe quantity again and stir, filter at last; Preferably, the described alcoholic acid amount 3.3-4.0% that is the injection gross weight.
Aforesaid preparing ginkgo biloba leaf extract injection, wherein said alkaline pH regulator is selected from one or more in sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium phosphate, sodium hydrogen phosphate, the sodium dihydrogen phosphate; Be preferably the 0.1mol sodium hydroxide.
Aforesaid preparing ginkgo biloba leaf extract injection, described method also comprise the step of aseptic filtration, fill injection.
Aforesaid preparing ginkgo biloba leaf extract injection, wherein said aseptic filtration are through 0.2 nano-film filtration; And/or wherein said fill step comprises that fill is to the back sterilization of ampere bottle.
The gingko leaf extract injection that the above-mentioned preparation method of a kind of foundation that the present invention also proposes makes.
A kind of method that improves the Folium Ginkgo extract dissolution rate that the present invention also proposes in addition, it may further comprise the steps: at first Folium Ginkgo extract is mixed with sorbitol; Add 95% an amount of ethanol, water for injection stirring then successively.
The present invention compared with prior art has tangible advantage and beneficial effect.By technique scheme, preparing ginkgo biloba leaf extract injection of the present invention and gingko leaf extract injection thereof have following advantage at least: the present invention has the effect that improves ginkgetin glycosides content under the same materials condition.
Figure of description
Figure 1A to Fig. 1 F is the reference substance of corresponding instance 1, the chromatogram of test sample.
Fig. 2 A to Fig. 2 F is the reference substance of corresponding Comparative Examples 1, the chromatogram of test sample.
Fig. 3 A to Fig. 3 F is the reference substance of corresponding instance 2, the chromatogram of test sample.
Fig. 4 A to Fig. 4 F is the reference substance of corresponding Comparative Examples 2, the chromatogram of test sample.
Fig. 5 A to Fig. 5 F is the reference substance of corresponding instance 3, the chromatogram of test sample.
Fig. 6 A to Fig. 6 F is the reference substance of corresponding Comparative Examples 3, the chromatogram of test sample.
Fig. 7 A to Fig. 7 F is the reference substance of corresponding instance 4, the chromatogram of test sample.
Fig. 8 A to Fig. 8 F is the reference substance of corresponding Comparative Examples 4, the chromatogram of test sample.
Fig. 9 A to Fig. 9 F is the reference substance of corresponding instance 5, the chromatogram of test sample.
Figure 10 A to Figure 10 F is the reference substance of corresponding Comparative Examples 5, the chromatogram of test sample.
Figure 11 A to Figure 11 F is the reference substance of corresponding instance 6, the chromatogram of test sample.
Figure 12 A to Figure 12 F is the reference substance of corresponding Comparative Examples 6, the chromatogram of test sample.
Figure 13 A to Figure 13 F is the reference substance of corresponding instance 7, the chromatogram of test sample.
Figure 14 A to Figure 14 F is the reference substance of corresponding Comparative Examples 7, the chromatogram of test sample.
Figure 15 A to Figure 15 F is the reference substance of corresponding instance 8, the chromatogram of test sample.
Figure 16 A to Figure 16 F is the reference substance of corresponding Comparative Examples 8, the chromatogram of test sample.
Figure 17 A to Figure 17 F is the reference substance of corresponding instance 9, the chromatogram of test sample.
Figure 18 A to Figure 18 F is the reference substance of corresponding Comparative Examples 9, the chromatogram of test sample.
Figure 19 A to Figure 19 F is the reference substance of corresponding instance 10, the chromatogram of test sample.
Figure 20 A to Figure 20 F is the reference substance of corresponding Comparative Examples 10, the chromatogram of test sample.
The specific embodiment
Reach technological means and the effect that predetermined goal of the invention is taked for further setting forth the present invention, below in conjunction with accompanying drawing and preferred embodiment, preparing ginkgo biloba leaf extract injection and its specific embodiment of gingko leaf extract injection, step, structure, feature and effect thereof that foundation the present invention is proposed describe in detail.
The preparing ginkgo biloba leaf extract injection of preferred embodiment of the present invention mainly comprises the step of blend step, dissolving step, adjust pH step and aseptic filtration, fill.
Above-mentioned blend step is that Folium Ginkgo extract is mixed with sorbitol (or mannitol).Mixing temperature is preferably and is lower than 30 ℃.For example can in super mixer, fully mix 20 minutes.The amount of sorbitol is a 5-6 times of weight of Folium Ginkgo extract.
Above-mentioned dissolving step is to add 95% an amount of ethanol, water for injection stirring in the mixture that makes in above-mentioned blend step successively, so that mixture fully dissolves.This dissolving step can be specific as follows but be not limited to following steps: in this mixture, add 95% ethanol and a certain amount of water for injection, continue to stir 30 minutes; Add 95% an amount of ethanol, water for injection and 0.1mol sodium hydroxide again, fully dissolving under stirring; Stirred 10-20 minute after adding water for injection again, filter and make lysate.Wherein, alcoholic acid amount is the 3.3-4.0% of injection gross weight.
Above-mentioned adjust pH step is to add the alkaline pH regulator to be adjusted to the physiology tolerance interval with the pH value with above-mentioned lysate.The alkaline pH regulator is selected from the combination of sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium phosphate, sodium hydrogen phosphate and sodium dihydrogen phosphate and above-mentioned substance.
In above-mentioned aseptic filtration, the step of fill, the aseptic filtration step is that the above-mentioned lysate of having regulated pH value is filtered through 0.2 micron membranes; The fill step is with in the filtrate fill to 5 of the aseptic filtration milliliter peace bottle.
Above-mentioned preparing ginkgo biloba leaf extract injection can also comprise the step that adds stabilizing agent.This step that adds antioxidant can be before or after this adjust pH step.The step of this interpolation stabilizing agent is that stabilizing agent is added in above-mentioned lysate or the above-mentioned lysate of regulating pH value.This stabilizing agent can be sodium sulfite, sodium pyrosulfite, cysteine, methionine, vitamin C or thiourea.The consumption of stabilizing agent is the liquor capacity percentage ratio of 0.05%-0.3%, and the best is 0.15%.
Above-mentioned preparing ginkgo biloba leaf extract injection can also comprise sterilization steps after the fill step.Sterilization steps be with in the fill step with after in the filtrate fill to 5 of the aseptic filtration milliliter peace bottle, in 121 ℃ of sterilizations 15 minutes.
Below by instantiation and Comparative Examples, the effect of the preparing ginkgo biloba leaf extract injection of preferred embodiment of the present invention is illustrated.
Example: by the gingko leaf extract injection preparation method preparation of preferred embodiment of the present invention.
Prescription:
Folium Ginkgo extract 17.5g
Sorbitol 96.25g
95% ethanol 150.0g
0.1mol sodium hydroxide is an amount of
Water for injection adds to 5000ml
Preparation technology:
Mix: the Folium Ginkgo extract and the sorbitol that take by weighing recipe quantity fully mixed 20 minutes in super mixer, and temperature is controlled at below 30 ℃;
Dissolving: the mixture in the blend step is transferred in the container, adds a small amount of 95% ethanol, a certain amount of water for injection, continue to stir 30 minutes; Add 95% an amount of ethanol, water for injection and 0.1mol sodium hydroxide again, fully dissolving under stirring; Add water for injection again and to 5000ml, stirred 10-20 minute, filter;
Adjust pH: the test previous step pH value of filtrate, and with 0.1mol sodium hydroxide solution adjust pH in the 5.7-7.3 scope;
Aseptic filtration: adjust pH is after the filtration of 0.2 micron membranes filter;
Fill and sterilization: filtrate fill to the 5 milliliter peace after the aseptic filtration is cutd open in the bottle, in the sterilization in following 15 minutes of 121 ℃ of temperature.
By above-mentioned prescription and preparation technology, repeat to make for 10 times the gingko leaf extract injection of example 1-10.
Comparative Examples:
Prescription:
Folium Ginkgo extract 17.5g
Sorbitol 96.25g
95% ethanol 150.0g
0.1mol sodium hydroxide is an amount of
Water for injection adds to 5000ml
Preparation technology:
Dissolving: take by weighing the Folium Ginkgo extract of recipe quantity and sorbitol to container, add a small amount of 95% ethanol, a certain amount of water for injection, continue to stir 30 minutes; Add 95% an amount of ethanol, water for injection and 0.1mol sodium hydroxide again, fully dissolving under stirring; Add water for injection again and to 5000ml, stirred 10-20 minute, filter;
Adjust pH: the test previous step pH value of filtrate, and with 0.1mol sodium hydroxide solution adjust pH in the 5.7-7.3 scope;
Aseptic filtration: adjust pH is after the filtration of 0.2 micron membranes filter;
Fill and sterilization: filtrate fill to the 5 milliliter peace after the aseptic filtration is cutd open in the bottle, in the sterilization in following 15 minutes of 121 temperature.
By above-mentioned prescription and preparation technology, repeat to make for 10 times the gingko leaf extract injection of Comparative Examples 1-10.
In previous examples and the Comparative Examples, Folium Ginkgo extract is the Folium Ginkgo extract that French Yi Dina company produces, and the content of ginkgetin glycosides is about 25.3% in this Folium Ginkgo extract; Sorbitol is the sorbitol that Nanning pharmaceutical Co. Ltd produces.Folium Ginkgo extract also can be bought the product of other companies of selling in the market; The consumption of Folium Ginkgo extract depends on the content of ginkgetin glycosides in the Folium Ginkgo extract in the prescription, and the inventory of the high more Folium Ginkgo extract of ginkgetin glycosides content is few more.
The test of example and Comparative Examples
Testing standard:
[discriminating] gets contrast Semen Ginkgo extrac (Standard Ginkgo Biloba Extract) about 5mg (or about 10mg), adds 80% methanol 1ml and makes dissolving, and product solution is tested according to thin layer chromatography (two appendix VB of Chinese Pharmacopoeia version in 2005) in contrast.Draw this product (gingko leaf extract injection that example or Comparative Examples make) 20 μ l, reference substance solution 10 μ l, put respectively on same polyamide lamellae, with water-ethanol-butanone-acetylacetone,2,4-pentanedione (65: 15: 15: be developing solvent 5), after the expansion, dry, put under the ultra-violet lamp (365nm) and inspect, in the chromatograph of this product, with the corresponding position of reference substance chromatograph on, show four identical yellow fluorescence speckles.
[assay] measured according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2005).
Chromatographic condition and system suitability testWith octadecyl silane is filler, and 0.6% citric acid-acetonitrile-isopropyl alcohol (100: 47: 5) is a mobile phase, detects wavelength 360nm, and theoretical cam curve is calculated by the Quercetin peak should be not less than 1000, and the separating degree of Quercetin and kaempferol should meet the requirements.
The preparation of reference substance solutionPrecision takes by weighing each about 5mg of Quercetin, isorhamnetin and kaempferol (or about 10mg), puts in the 50ml measuring bottle, is diluted to scale with methanol, shakes up.
The preparation of need testing solutionPrecision takes by weighing this product (gingko leaf extract injection that example or Comparative Examples make) 15ml, put in the 50ml measuring bottle, add hydrochloric acid solution (6mol/L) 5ml, be diluted to scale, shake up with methanol, get 10ml, put in the brown tool lid test tube, screw in the rearmounted boiling water bath of lid, heated 25 minutes, take out, be cooled to room temperature.
AlgoscopyGet each 10 μ of reference substance solution and need testing solution l*2 time, inject chromatograph of liquid, the record chromatogram, with calculated by peak area, peak area is got 2 times meansigma methods by external standard method, and presses the following formula conversion.
The injection content (being 15/50=0.3) of the Quercetin of example (or kaempferol or isorhamnetin) content=test sample Quercetin (or kaempferol or isorhamnetin) peak area/reference substance Quercetin (or kaempferol or isorhamnetin) peak area * reference substance Quercetin (or kaempferol or isorhamnetin) content/test sample
Quercetin glycosides content (mg/ml)=quercetin content (mg/ml) * 2.504
The content (mg/ml) * 2.588 of content (mg/ml)=(kaempferol+isorhamnetin) of (Rhizoma Kaempferiae phenolic glycoside+isorhamnetin glycosides)
The content (mg/ml) of ginkgetin glycosides content (mg/ml)=Quercetin glycosides content (mg/ml)+(Rhizoma Kaempferiae phenolic glycoside+isorhamnetin glycosides)
With example 1 is the method that example specifies test ginkgetin glycosides content:
Make reference substance solution and calculate content
Take by weighing Quercetin 5.43mg, isorhamnetin 5.17mg and kaempferol 5.26mg put in the 50ml measuring bottle, add dissolve with methanol and are diluted to scale (50ml).Wherein the purity of Quercetin is 97.3%, and quercetin content is 5.43/50*97.3%=0.106mg/ml in the reference substance solution; Wherein the purity of isorhamnetin is 100%, and isorhamnetin content is 5.17/50*100%=0.103mg/ml in the reference substance solution; Wherein the purity of kaempferol is 95.9%, and kaempferol content is 5.43/50*95.9%=0.101mg/ml in the reference substance solution.
Get above-mentioned reference substance solution 10 μ l*2 time, inject Tianjin, island LC-20AT type chromatograph of liquid, record chromatogram (as Figure 1A, Figure 1B).The content and the test data of above-mentioned reference substance solution are recorded in table 1.
The data of the reference substance of table 1 corresponding instance 1
Illustrate: the data among the corresponding Figure 1A of 1 appearance time of solution and peak area; Data among the corresponding Figure 1B of 2 appearance times of solution and peak area.
Reference substance is made sample twice, is the degree of accuracy for the verification test instrument, and (RSD is meant relative standard deviation to RSD＜2%, is used to refer to the precision of sample introduction data.)。
The need testing solution of example of making 1 and test content
The gingko leaf extract injection 15ml twice that treating excess syndrome example 1 makes adds hydrochloric acid solution (6mol/L) 5ml respectively and is diluted to 50ml with methanol, makes example 1 need testing solution I and example 1 need testing solution II.
Each 10 μ l* for the treatment of excess syndrome example 1 need testing solution I and example 1 need testing solution II each 2 times inject chromatograph of liquid, write down four times chromatogram, are respectively Fig. 1 C, Fig. 1 D, Fig. 1 F, Fig. 1 F.Above-mentioned need testing solution test color spectral data and result of calculation are recorded in table 2.
The test data of the test sample of table 2 example 1
Illustrate: 1 appearance time of need testing solution I and the data among the peak area corresponding diagram 1C; 2 appearance times of need testing solution I and the data among the peak area corresponding diagram 1D; 1 appearance time of need testing solution II and the data among the peak area corresponding diagram 1E; 2 appearance times of need testing solution II and the data among the peak area corresponding diagram 1F.
Make test sample I and test sample II and be and do the calibration exactness for description operation person.It is true to do calibration as two close then explanations of data result.Each test sample is made sample twice, and the degree of accuracy of test instrunment then is described, (RSD is meant relative standard deviation to RSD＜2%, is used to refer to the precision of sample introduction data.)。
By above-mentioned table 2 as can be known, the content of ginkgetin glycosides is 0.849mg/ml in the gingko leaf extract injection of example 1.
Test data statistics after the gingko leaf extract injection test of example and Comparative Examples is as follows:
The content of Quercetin, isorhamnetin or kaempferide in the reference substance solution of table 3 example 1-10 and Comparative Examples 1-10
The ginkgetin glycosides content of each example and each Comparative Examples, test result is recorded in the table 4.
Table 4, the ginkgetin glycosides content of example 1-10 and Comparative Examples 1-10
Make ginkgetin glycosides content measurement result (table 4) in the gingko leaf extract injection at each example and each Comparative Examples, with statistical two groups of sample T check back P＜0.01, the flavonoid glycoside content that shows example set (example 1-10) and Comparative Examples group (Comparative Examples 1-10) has significant difference, and the content of example set ginkgetin glycosides is with respect to Comparative Examples group mean height more than 12%.The preparing ginkgo biloba leaf extract injection of preferred embodiments of the present invention can improve the content of ginkgetin glycosides under the same materials condition.
The present invention also provides the gingko leaf extract injection that makes by above-mentioned preparing ginkgo biloba leaf extract injection.
The gingko leaf extract injection of example 1-10 preparation of the present invention proves anaphylaxis is not appearred in the blood vessel nonirritant yet through animal experiment.The resulting Folium Ginkgo extract injection of the present invention is very little through animal acute toxicity test proof toxicity.
Though the present invention discloses as above with preferred embodiment, so be not in order to limiting scope of the invention process, the simple equivalent of doing according to claims of the present invention and description changes and modifies, and still belongs in the scope of technical solution of the present invention.
Claims (10)
1. a preparing ginkgo biloba leaf extract injection is characterized in that, said method comprising the steps of:
Blend step mixes Folium Ginkgo extract with sorbitol or mannitol;
Dissolving step adds 95% an amount of ethanol, water for injection stirring successively; And
The adjust pH step adds the alkaline pH regulator pH value is adjusted to pH 5.7-7.3.
2. preparing ginkgo biloba leaf extract injection as claimed in claim 1 is characterized in that the temperature of wherein said blend step is less than 30 ℃.
3. preparing ginkgo biloba leaf extract injection as claimed in claim 1 or 2 is characterized in that, the weight ratio of wherein said Folium Ginkgo extract and sorbitol or mannitol is 1: 5-6.
4. as each described preparing ginkgo biloba leaf extract injection in the claim 1 to 3, it is characterized in that, wherein before or after the adjust pH step, also comprise the step that adds stabilizing agent.
5. as each described preparing ginkgo biloba leaf extract injection in the claim 1 to 4, it is characterized in that wherein said stabilizing agent is selected from one or more in sodium sulfite, sodium pyrosulfite, sodium sulfite, sodium pyrosulfite, cysteine, methionine, vitamin C or the thiourea; Preferably, the consumption of described stabilizing agent is the injection volume percentage ratio of 0.05%-0.3%, more preferably 0.15%.
6. as each described preparing ginkgo biloba leaf extract injection in the claim 1 to 5, it is characterized in that, wherein said dissolving step comprises: add a small amount of 95% ethanol, water for injection stirring earlier, adding an amount of 95% ethanol, water for injection and 0.1mol sodium hydroxide again stirs, add injection water to recipe quantity again and stir, filter at last; Preferably, the described alcoholic acid amount 3.3-4.0% that is the injection gross weight.
7. as each described preparing ginkgo biloba leaf extract injection in the claim 1 to 6, it is characterized in that wherein said alkaline pH regulator is selected from one or more in sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium phosphate, sodium hydrogen phosphate, the sodium dihydrogen phosphate; Be preferably the 0.1mol sodium hydroxide.
8. as each described preparing ginkgo biloba leaf extract injection in the claim 1 to 7, it is characterized in that described method also comprises the step of aseptic filtration, fill injection.
9. as each described preparing ginkgo biloba leaf extract injection in the claim 1 to 8, it is characterized in that wherein said aseptic filtration is through 0.2 nano-film filtration; And/or wherein said fill step comprises that fill is to the back sterilization of ampere bottle.
10. one kind by the gingko leaf extract injection that makes as each described preparation method in the claim 1 to 9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010233165 CN101890061B (en) | 2010-07-16 | 2010-07-16 | Method for preparing ginkgo biloba leaf extract injection, and ginkgo biloba leaf extract injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010233165 CN101890061B (en) | 2010-07-16 | 2010-07-16 | Method for preparing ginkgo biloba leaf extract injection, and ginkgo biloba leaf extract injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101890061A true CN101890061A (en) | 2010-11-24 |
| CN101890061B CN101890061B (en) | 2012-04-18 |
Family
ID=43099518
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010233165 Active CN101890061B (en) | 2010-07-16 | 2010-07-16 | Method for preparing ginkgo biloba leaf extract injection, and ginkgo biloba leaf extract injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101890061B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110967426A (en) * | 2019-12-19 | 2020-04-07 | 华润三九（雅安）药业有限公司 | Enrichment method and content determination method of free quercetin in safflower injection |
| CN111213512A (en) * | 2020-01-13 | 2020-06-02 | 广东省农业科学院果树研究所 | Planting method for improving total flavone content and antioxidant activity of wampee fruits |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1099294C (en) * | 1999-12-09 | 2003-01-22 | 上海市中药研究所 | Process for preparing gingko injection |
| CN1448172A (en) * | 2003-04-30 | 2003-10-15 | 江苏扬子江药业集团有限公司 | Folium ginkgo injection and preparation thereof |
| CN1517088A (en) * | 2003-01-14 | 2004-08-04 | 宏 李 | Ginkgo leaf extract injection and its preparation method |
| CN1172703C (en) * | 2002-06-11 | 2004-10-27 | 张平 | Gingko leaf powder for injection and its prepn. |
| CN1586550A (en) * | 2004-07-16 | 2005-03-02 | 北京国仁堂医药科技发展有限公司 | Process for preparing ginkgo leaf extract powder injection |
| CN100421680C (en) * | 2005-08-10 | 2008-10-01 | 北京星昊医药股份有限公司 | Extractive of ginkgo tree leaves, prepn. method and application thereof |
| CN100446778C (en) * | 2007-04-18 | 2008-12-31 | 黑龙江省珍宝岛制药有限公司 | Method of preparing solution / substance extracted from ginkgo leaves |
| CN100496518C (en) * | 2005-07-18 | 2009-06-10 | 厦门国宇知识产权研究有限公司 | Ginkgo leaf extract, injection containing said extract and its preparing method |
| CN101596222A (en) * | 2009-06-22 | 2009-12-09 | 北京中海康医药科技发展有限公司 | A kind of refined ginkgo biloba extract, powder pin and preparation method thereof |
-
2010
- 2010-07-16 CN CN 201010233165 patent/CN101890061B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1099294C (en) * | 1999-12-09 | 2003-01-22 | 上海市中药研究所 | Process for preparing gingko injection |
| CN1172703C (en) * | 2002-06-11 | 2004-10-27 | 张平 | Gingko leaf powder for injection and its prepn. |
| CN1517088A (en) * | 2003-01-14 | 2004-08-04 | 宏 李 | Ginkgo leaf extract injection and its preparation method |
| CN1448172A (en) * | 2003-04-30 | 2003-10-15 | 江苏扬子江药业集团有限公司 | Folium ginkgo injection and preparation thereof |
| CN1586550A (en) * | 2004-07-16 | 2005-03-02 | 北京国仁堂医药科技发展有限公司 | Process for preparing ginkgo leaf extract powder injection |
| CN100496518C (en) * | 2005-07-18 | 2009-06-10 | 厦门国宇知识产权研究有限公司 | Ginkgo leaf extract, injection containing said extract and its preparing method |
| CN100421680C (en) * | 2005-08-10 | 2008-10-01 | 北京星昊医药股份有限公司 | Extractive of ginkgo tree leaves, prepn. method and application thereof |
| CN100446778C (en) * | 2007-04-18 | 2008-12-31 | 黑龙江省珍宝岛制药有限公司 | Method of preparing solution / substance extracted from ginkgo leaves |
| CN101596222A (en) * | 2009-06-22 | 2009-12-09 | 北京中海康医药科技发展有限公司 | A kind of refined ginkgo biloba extract, powder pin and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110967426A (en) * | 2019-12-19 | 2020-04-07 | 华润三九（雅安）药业有限公司 | Enrichment method and content determination method of free quercetin in safflower injection |
| CN111213512A (en) * | 2020-01-13 | 2020-06-02 | 广东省农业科学院果树研究所 | Planting method for improving total flavone content and antioxidant activity of wampee fruits |
| CN111213512B (en) * | 2020-01-13 | 2021-10-12 | 广东省农业科学院果树研究所 | Planting method for improving total flavone content and antioxidant activity of wampee fruits |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101890061B (en) | 2012-04-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100522163C (en) | Small volume vincamine injection and its preparation process | |
| CN103623059B (en) | A kind of pharmaceutical composition and application thereof, containing its medicament | |
| CN102346177A (en) | Method for detecting Simotang preparation | |
| CN109464531A (en) | A kind of preparation method of danggui liuhuang decoction | |
| CN104666474A (en) | Spina date seed extract and brain-strengthening and sleeping-promoting oral liquid containing spina date seed extract | |
| CA2702711A1 (en) | Liquid preparation containing herb and/or animal-origin extract | |
| CN101890061B (en) | Method for preparing ginkgo biloba leaf extract injection, and ginkgo biloba leaf extract injection | |
| CN103645251B (en) | A kind of fingerprint atlas detection method of compound donkey-hide gelatin preparation | |
| CN102641317A (en) | Golden wave extract and application thereof in preparation of antidiabetic agent | |
| CN108685856B (en) | Pediatric paracetamol granule and preparation method thereof | |
| CN109280042A (en) | A kind of method of biflavone compound in extraction ginkgo leaf | |
| CN101810629B (en) | Composition injection of glycerol and fructose and preparation method thereof | |
| CN102846704B (en) | A Leonurus japonicus injection, its preparation method, and method for detecting total alkaloids | |
| CN104337811A (en) | Repaglinide-metformin hydrochloride tablet and preparing method thereof | |
| CN1814048B (en) | Chinese medicine liquid capsule of Folium callicarpae Nudiflorae, preparing method and quality control method | |
| CN1939357B (en) | Preparation of Ginkgo Damo injection | |
| CN110196299A (en) | The finger-print of diplopia ' Yanming ' capsules for clearing and its application in quality control and constituent analysis | |
| CN103091408B (en) | Method for determining content of hesperidin in Citrus Bioflavonoids | |
| CN102353731A (en) | Method for detecting astragalus-chickpea particles | |
| CN105147724B (en) | A kind of Mannitol sodium chloride injection and preparation method thereof | |
| CN1839985B (en) | Quality control method for cleaning liquor and its derivative formulation for female | |
| CN101991663B (en) | Liquid total paeony glycoside composite and preparation method thereof | |
| CN101762581A (en) | Quick screening method for Chinese medicinal herb weight-reducing product doped with sibutramine hydrochloride | |
| CN105997898B (en) | Fat-soluble vitamin for injection I powder-injection composition and preparation method | |
| CN106279315B (en) | One kind preparing Quercetin -3-O-2 from ginkgo biloba p.e ", the method for 6 "-two rhamnopyranosyl glucosides |
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 | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Method for preparing ginkgo biloba leaf extract injection, and ginkgo biloba leaf extract injection Effective date of registration: 20161219 Granted publication date: 20120418 Pledgee: China Development Bank Co Pledgor: Yuekang Pharmaceutical Group Co., Ltd. Registration number: 2016990001120 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20180206 Granted publication date: 20120418 Pledgee: National Development Bank Pledgor: Yuekang Pharmaceutical Group Co., Ltd. Registration number: 2016990001120 |
|
| PM01 | Change of the registration of the contract for pledge of patent right | ||
| PM01 | Change of the registration of the contract for pledge of patent right |
Change date: 20180206 Registration number: 2016990001120 Pledgee after: National Development Bank Pledgee before: China Development Bank Co |
|
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 100176 No. 6, Hongda Middle Road, Beijing Economic Development Zone, Beijing Patentee after: Yuekang Pharmaceutical Group Co., Ltd. Address before: 100176 No. 6, Hongda Middle Road, Beijing Economic Development Zone, Beijing Patentee before: YOUCARE PHARMACEUTICAL GROUP CO., LTD. |