CN1393484A - Inclusion compound of ginsenoside RG3 and hydroxypropyl-beta-cyclodextrin and its preparation and preparing process - Google Patents
Inclusion compound of ginsenoside RG3 and hydroxypropyl-beta-cyclodextrin and its preparation and preparing process Download PDFInfo
- Publication number
- CN1393484A CN1393484A CN 01119929 CN01119929A CN1393484A CN 1393484 A CN1393484 A CN 1393484A CN 01119929 CN01119929 CN 01119929 CN 01119929 A CN01119929 A CN 01119929A CN 1393484 A CN1393484 A CN 1393484A
- Authority
- CN
- China
- Prior art keywords
- beta
- hydroxypropyl
- cyclodextrin
- panaxoside
- inclusion
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 41
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 title claims description 29
- 238000002360 preparation method Methods 0.000 title claims description 18
- RWXIFXNRCLMQCD-JBVRGBGGSA-N (20S)-ginsenoside Rg3 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4[C@@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RWXIFXNRCLMQCD-JBVRGBGGSA-N 0.000 title abstract description 31
- XIRZPICFRDZXPF-UHFFFAOYSA-N Ginsenoside Rg3 Natural products CC(C)=CCCC(C)(O)C1CCC(C2(CC(O)C3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O XIRZPICFRDZXPF-UHFFFAOYSA-N 0.000 title abstract description 12
- 238000000034 method Methods 0.000 title description 18
- 238000002347 injection Methods 0.000 claims abstract description 12
- 239000007924 injection Substances 0.000 claims abstract description 12
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 239000007864 aqueous solution Substances 0.000 claims abstract description 8
- 239000000843 powder Substances 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims abstract description 8
- 238000001035 drying Methods 0.000 claims abstract description 6
- 239000002775 capsule Substances 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 7
- 229930182494 ginsenoside Natural products 0.000 claims description 7
- 229940089161 ginsenoside Drugs 0.000 claims description 7
- 239000002994 raw material Substances 0.000 claims description 7
- 239000012982 microporous membrane Substances 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 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 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 239000008215 water for injection Substances 0.000 claims description 3
- 238000012856 packing Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 241000208340 Araliaceae Species 0.000 claims 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 claims 1
- 235000003140 Panax quinquefolius Nutrition 0.000 claims 1
- 235000008434 ginseng Nutrition 0.000 claims 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims 1
- 229930182490 saponin Natural products 0.000 claims 1
- 150000007949 saponins Chemical class 0.000 claims 1
- 229920001353 Dextrin Polymers 0.000 abstract 2
- 239000003826 tablet Substances 0.000 abstract 1
- 208000002463 Sveinsson chorioretinal atrophy Diseases 0.000 description 10
- 239000000203 mixture Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004455 differential thermal analysis Methods 0.000 description 3
- 241000580923 Acer buergerianum Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- -1 steroid compound Chemical class 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
An inclusion compound is prepared from ginsenoside RG3 and hydroxypropyl-beta-dextrine in wt. ratio of 1:(1-100) through dissolving ginsenoside RG3 in organic solvent, adding it to the aqueous solution of hydroxypropyl-beta-dextrine, stirring, and then drying. It can be used to prepare freeze-dried powder injection, tablet, or capsule.
Description
The present invention relates to hydroxypropyl-beta-cyclodextrin inclusion and the preparation and the preparation method of panaxoside Rg 3, this compound can be used to injection or oral.
Panaxoside Rg 3 is to extract a kind of chemical ingredients that obtains from genseng, also can obtain by semisynthetic method, and this has obtained describing in detail at document and patent.Panaxoside Rg 3 has stronger antitumous effect, and it all has strong restraining effect to lung cancer, cancer of the stomach, lymphatic cancer, and suppresses the metastasis of cancer, clinical research confirmation, and these product are oral and injection is all effective.
Because panaxoside Rg 3 is a kind of materials that are insoluble in water and oil, has greatly reduced its bioavailability, has limited the performance of drug effect, simultaneously, has limited the approach of parenterai administration.Improve panaxoside Rg 3 solvabilities and become the key that solves its bioavailability and injection.Scheme in the past can adopt and add solubility promoter or be prepared as salt, perhaps it is prepared as emulsion.Adopt tween, dimethyl trident maple can make its solubleness that faint raising is arranged through test, but bring toxic action thus, discomfort is fit to do injection.And, be difficult to be prepared into emulsion because panaxoside Rg 3 is insoluble to oil.By retrieval, the patent that relates to panaxoside Rg 3 is synthetic preparation patent substantially, finds no to close and uses hydroxypropyl-beta-cyclodextrin that panaxoside Rg 3 is carried out the inclusion patent.
The hydroxypropyl-beta-cyclodextrin inclusion and preparation and the preparation method that the purpose of this invention is to provide a kind of panaxoside Rg 3.This method is utilized cyclodextrin encapsulated effect, with panaxoside Rg 3 inclusions, makes it water-soluble.Panaxoside Rg 3 is a steroid compound, and molecular weight is 784, and molecular formula is C
42H
72O
13Hydroxypropyl-beta-cyclodextrin is a cyclodextrin derivative, and it has the tubular molecular structure.Molecular weight is 1540, have water-soluble, the inclusion amount is big, the characteristics that toxicity is low, and can be used for injection, because the Rg3 molecule is bigger, bag and time analysis may by a plurality of hydroxypropyl-beta-cyclodextrins (molecule of HP-β-CD) with Fan Dehuali with its inclusion, through the test, Rg3 and HP-β-CD by certain weight ratio inclusion after ginsenoside Rg3 solubleness improve than before more than 1000 times, reach water-soluble by water insoluble.
The objective of the invention is to be achieved through the following technical solutions:
It is made of by weight following raw material:
Ginsenoside: hydroxypropyl-beta-cyclodextrin=1: 1-200;
Preparation method of the present invention is:
Panaxoside Rg 3 is dissolved in the organic solvent by above-mentioned weight ratio, be generally in the mixed solvent of chloroform, methyl alcohol, water or methylene dichloride,, in the mixed solvent of methyl alcohol, water or in the methyl alcohol.Hydroxypropyl-beta-cyclodextrin HPCD is soluble in water by above-mentioned weight ratio.To contain the aqueous solution violent stirring of HPCD, slowly drip Rg3 solution, after all adding, continue to stir 2-24 hour, use 0.45 μ m filtering with microporous membrane, filtrate is concentrated, eliminate organic solvent, add an amount of injection water, again dissolving is crossed 0.22 μ m film, the filtrate lyophilize, the white powder that must loosen is panaxoside Rg 3 inclusion compounds.
Inclusion compound of the present invention also can adopt other method preparation, as polishing, is about to panaxoside Rg 3 addings and grinds among the equal HPCD, grinds all, and cryodrying gets inclusion compound.Perhaps adopt spray drying method for preparation.Inclusion compound with this quadrat method preparation can be used for oral raw material.
Panaxoside Rg 3 is 1 with the weight ratio of HPCD in the inclusion compound among the present invention: 1-200, and wherein with 1: 60-100 ratio solubleness maximum.And the ratio of the two is 1: 1 o'clock, and existing inclusion compound forms, and this moment, the two weight ratio was 1: 2, but not more by the Rg3 of inclusion during this ratio, the Rg3 loss is bigger, and with 1: 100 ratio, the Rg3 inclusion rate was the highest, and inclusion rate can reach 86%.
Organic solvent can also be two subunit trident maples, tween, and mix reagent among the present invention.
The inclusion compound that obtains by the present invention is characterized by and contains panaxoside Rg 3 and two kinds of chemical ingredientss of HPCD, and soluble in water, and its DSC differential thermal analysis spectrogram does not have Rg3 fusing point peak (260 ℃-270 ℃), has only the endotherm(ic)peak relevant with HPCD.Phase solubility method and approach into the formation that chromatography proves this inclusion compound.
Inclusion compound among the present invention can directly be prepared into oral preparations, as capsule, also can add certain auxiliary material, beats sheet, makes tablet.
Inclusion compound of the present invention can add a kind of adjusting osmotic pressure auxiliary material in technology, as N.F,USP MANNITOL, lactose etc., after the lyophilize, make freeze-dried powder.
The invention has the advantages that the HPCD inclusion compound that a kind of panaxoside Rg 3 soluble in water is provided, can improve its stability simultaneously, improve its bioavailability, but a kind of panaxoside Rg 3 of injection is provided.
Inclusion compound among the present invention proves by the following method that mainly one adopts the phase solubility method to measure its inclusion compound and whether forms.Its method is to get the panaxoside Rg 3 of 50mg, be added in HPCD (hydroxypropyl-beta-cyclodextrin) solution that contains different concns, stirred 24 hours, with 0.45 μ m filtering with microporous membrane, get filtrate, adopt the HPLC method to measure panaxoside Rg 3 concentration, draw its solubility curve, prove the formation of its inclusion compound.Its two pairs of inclusion compounds are made the DSC differential thermal analysis, find that inclusion compound does not have Rg3 fusing point peak (260 ℃-270 ℃), and mixture have Rg3 fusing point peak (260 ℃-270 ℃), illustrates that this product is a molecular clathrate.Its three employings tlc is used inclusion compound and Rg3 and mixture point sample simultaneously, confirms to have formed inclusion compound.
Fig. 1 is the DSC spectrogram of ginsenoside Rg3.
Fig. 2 is the DSC spectrogram of hydroxypropyl-beta-cyclodextrin.
Fig. 3 is the hydroxypropyl-beta-cyclodextrin inclusion DSC spectrogram of ginsenoside Rg3.
Fig. 4 is the hydroxypropyl-beta-cyclodextrin mixture D SC spectrogram of ginsenoside Rg3.
Fig. 5 is a thin-layer chromatogram.
Fig. 6 is a ginsenoside Rg3HPCD solubilising curve.
It is soluble in water that phase solubility-curve draws the Ginsenoside Rg3 inclusion compound from Fig. 6, fully Be different from the water-fast character of Rg3, prove to have formed inclusion compound. Fig. 1 to Fig. 4 illustrates, The DSC curve of Ginsenoside Rg3 inclusion compound is different from the Rg3 curve, produces new phase, its The fusing point peak does not occur in inclusion compound, and mixture comprises Rg3 fusing point peak. Among Fig. 1, Rg3 Aqueous solution point sample be speckless, and inclusion compound and Rg3 methanol solution spot have same Rf Value illustrates the formation of inclusion compound.
Ginsenoside Rg3 and inclusion compound analysis determining method thereof adopt high-efficient liquid phase technique, its system Mobile phase is methyl alcohol: water=90: 10, detect wavelength 203nm, flow velocity 1ml min, the C18 post. The Rg3 inclusion compound has identical retention time with Rg3. Ginsenoside Rg3 Tlc Determination side Method is: solvent is chloroform: methyl alcohol: water (6: 4: 1), silica gel g thin-layer plate, developer 10% ethanol solution of sulfuric acid, 110 ℃ were heated 10 minutes. Differential thermal analysis (DSC) analysis condition is 5 ℃ of min of programming rate
Get panaxoside Rg 3 100mg, get HP-β-CD10000mg, HPCD is dissolved in the 100ml water, magnetic agitation is dissolved in minimum of chloroform with Rg3: methyl alcohol: in water (6: 4: the 1) solvent, dropwise add in the aqueous solution that contains HPCD, stirred then 3 hours, use 0.45 μ m filtering with microporous membrane, filtrate decompression is concentrated into original volume 1/3, to eliminate organic solvent, add water for injection to 1 times of commercial weight, with 0.22 μ m filtration sterilization, aseptic then lyophilize, get the white loose powder, measure through high-efficient liquid phase technique, contain panaxoside Rg 3 86mg in this inclusion compound, inclusion rate 86%, the DSC spectrum confirms to have formed inclusion compound.
Embodiment 2
Get panaxoside Rg 3 100mg, HPCD400mg presses embodiment 1 method, makes inclusion compound, measures through the HPLC method, and inclusion compound contains Rg3 10mg.
Embodiment 3
Get panaxoside Rg 3 100mg, add among the 1000mgHPCD, ground 3 hours, drying under reduced pressure gets inclusion compound.
Embodiment 4
Change the drying means among the embodiment 1 into spray-drying process, other is with embodiment 1.
With embodiment 1, add water for injection after, add an amount of N.F,USP MANNITOL, regulate to wait and ooze, the ultra-fine filter with molecular weight cut-off 5000 removes thermal source then, filtrate is with 0.22 μ m filtering with microporous membrane degerming, packing, lyophilize gets the injection freeze-dried powder.
Embodiment 6
Get embodiment 1 inclusion compound, add appropriate amount of auxiliary materials, as N.F,USP MANNITOL, lactose, starch etc., compressing tablet is made tablet or is made capsule.
Claims (6)
1. the hydroxypropyl-beta-cyclodextrin inclusion of a panaxoside Rg 3, it by following raw material by weight forming: ginsenoside: hydroxypropyl-beta-cyclodextrin=1: 1-200; Join in the aqueous solution that contains hydroxypropyl-beta-cyclodextrin by the panaxoside Rg 3 that will be dissolved in organic solvent, after the stirring, drying forms inclusion compound soluble in water.
2. by the hydroxypropyl-beta-cyclodextrin inclusion of the described panaxoside Rg 3 of claim 1, it is made of by weight following raw material: ginsenoside: hydroxypropyl-beta-cyclodextrin=1: 60-100.
3. the preparation method of the hydroxypropyl-beta-cyclodextrin inclusion of panaxoside Rg 3, it by following raw material by weight forming:
Ginsenoside: hydroxypropyl-beta-cyclodextrin=1: 1-200;
Panaxoside Rg 3 is dissolved in the organic solvent, be generally in the mixed solvent of chloroform, methyl alcohol, water or the mixed solvent of methylene dichloride, methyl alcohol, water in; Hydroxypropyl-beta-cyclodextrin is soluble in water; The aqueous solution violent stirring that will contain hydroxypropyl-beta-cyclodextrin slowly is added dropwise to ginseng saponin Rg3 solution, after all adding, continue to stir 2-24 hour, use 0.45 μ m filtering with microporous membrane, filtrate is concentrated, eliminate organic solvent, add injection water, again dissolving is crossed 0.22 μ m film, the filtrate lyophilize, the white powder that must loosen is panaxoside Rg 3 inclusion compounds.
4. the hydroxypropyl-beta-cyclodextrin inclusion preparation of a panaxoside Rg 3, it by following raw material by weight forming: ginsenoside: hydroxypropyl-beta-cyclodextrin=1: 1-200 also comprises the injectable drug carrier; Join in the aqueous solution that contains hydroxypropyl-beta-cyclodextrin by the panaxoside Rg 3 that will be dissolved in organic solvent, after the stirring, drying forms inclusion compound soluble in water; Add pharmaceutical carrier, get inclusion compound preparation, i.e. injection freeze-dried powder.
5. press the preparation method of the hydroxypropyl-beta-cyclodextrin inclusion of the described panaxoside Rg 3 of claim 3, also comprise the steps: after adding water for injection in the described inclusion compound, add N.F,USP MANNITOL or lactose, regulate to wait and ooze, remove thermal source with the ultra-fine filter of molecular weight cut-off 5000 then, filtrate is with 0.22 μ m filtering with microporous membrane degerming, packing, lyophilize gets the injection freeze-dried powder.
6. the hydroxypropyl-beta-cyclodextrin inclusion preparation of a panaxoside Rg 3, it by following raw material by weight forming: ginsenoside: hydroxypropyl-beta-cyclodextrin=1: 1-200 also comprises excipient substance; Join in the aqueous solution that contains hydroxypropyl-beta-cyclodextrin by the panaxoside Rg 3 that will be dissolved in organic solvent, after the stirring, drying forms inclusion compound soluble in water; Add excipient substance, make tablet or make capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011199296A CN1167734C (en) | 2001-07-02 | 2001-07-02 | Inclusion compound of ginsenoside RG3 and hydroxypropyl-beta-cyclodextrin and its preparation and preparing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011199296A CN1167734C (en) | 2001-07-02 | 2001-07-02 | Inclusion compound of ginsenoside RG3 and hydroxypropyl-beta-cyclodextrin and its preparation and preparing process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1393484A true CN1393484A (en) | 2003-01-29 |
| CN1167734C CN1167734C (en) | 2004-09-22 |
Family
ID=4663808
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB011199296A Expired - Fee Related CN1167734C (en) | 2001-07-02 | 2001-07-02 | Inclusion compound of ginsenoside RG3 and hydroxypropyl-beta-cyclodextrin and its preparation and preparing process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1167734C (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007134534A1 (en) * | 2006-05-22 | 2007-11-29 | Li Fu | WATER SOLUTION OF 20(R)-GINSENOSIDE Rg3 PHARMACEUTICAL COMPOSITION AND PROCESS THEREOF |
| WO2007134533A1 (en) * | 2006-05-22 | 2007-11-29 | Li Fu | 20(R)-GINSENOSIDE Rg3 MEDICINAL SOLUBLE INTERMEDIATE AND PROCESS THEREOF |
| CN101138545B (en) * | 2006-09-08 | 2010-07-21 | 广州天安医药科技有限公司 | Clathrate compound containing ginsenoside Rg2 and method of preparing the same |
| WO2012100408A1 (en) * | 2011-01-25 | 2012-08-02 | 河北以岭医药研究院有限公司 | Dextrin inclusion complex, preparation method thereof and pharmaceutical formulation comprising said inclusion complex |
| CN102008494B (en) * | 2006-05-22 | 2013-05-08 | 富力 | 20(R)-ginsenoside Rg3 medicinal water-solubility intermediate, freeze-dried powder injection and preparation method thereof |
| CN104561219A (en) * | 2014-12-16 | 2015-04-29 | 江南大学 | Method of enzymatically synthesizing ginsenoside Rh2 |
| CN116251060A (en) * | 2023-04-24 | 2023-06-13 | 朗天药业(湖北)有限公司 | Digoxin injection and preparation method thereof |
-
2001
- 2001-07-02 CN CNB011199296A patent/CN1167734C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007134534A1 (en) * | 2006-05-22 | 2007-11-29 | Li Fu | WATER SOLUTION OF 20(R)-GINSENOSIDE Rg3 PHARMACEUTICAL COMPOSITION AND PROCESS THEREOF |
| WO2007134533A1 (en) * | 2006-05-22 | 2007-11-29 | Li Fu | 20(R)-GINSENOSIDE Rg3 MEDICINAL SOLUBLE INTERMEDIATE AND PROCESS THEREOF |
| CN102008494B (en) * | 2006-05-22 | 2013-05-08 | 富力 | 20(R)-ginsenoside Rg3 medicinal water-solubility intermediate, freeze-dried powder injection and preparation method thereof |
| US8487090B2 (en) | 2006-05-22 | 2013-07-16 | Dalian Fusheng Natural Medicine Development Co., Ltd. | Water solution of 20(R)-ginsenoside Rg3 pharmaceutical composition and process thereof |
| US9333215B2 (en) | 2006-05-22 | 2016-05-10 | Li Fu | Aqueous solution of 20(R)-ginsenoside RG3 pharmaceutical composition and process thereof |
| CN101138545B (en) * | 2006-09-08 | 2010-07-21 | 广州天安医药科技有限公司 | Clathrate compound containing ginsenoside Rg2 and method of preparing the same |
| WO2012100408A1 (en) * | 2011-01-25 | 2012-08-02 | 河北以岭医药研究院有限公司 | Dextrin inclusion complex, preparation method thereof and pharmaceutical formulation comprising said inclusion complex |
| CN104561219A (en) * | 2014-12-16 | 2015-04-29 | 江南大学 | Method of enzymatically synthesizing ginsenoside Rh2 |
| CN116251060A (en) * | 2023-04-24 | 2023-06-13 | 朗天药业(湖北)有限公司 | Digoxin injection and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1167734C (en) | 2004-09-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5684169A (en) | Cyclodextrin inclusion complex of taxol, and method for its production and its use | |
| EP0056995B1 (en) | Chemical complex | |
| KR900000542B1 (en) | Inclusion complex of 7-isopropoxy-isflavon,the preparation thereof | |
| US7678776B2 (en) | Inclusion complexes of butylphthalide with cyclodextrin or its derivatives, a process for their preparation and the use thereof | |
| CN100486645C (en) | Medicine composition containing cyclodextrin included taxol and its preparation process | |
| Lee et al. | Physicochemical characteristics and bioavailability of a novel intestinal metabolite of ginseng saponin (IH901) complexed with β-cyclodextrin | |
| CN100384477C (en) | Complex of modafinil and cyclodextrin | |
| US11931451B2 (en) | Skin lightening compounds from fruit seed extracts | |
| JP2022531510A (en) | Inclusions containing non-psychotropic cannabinoids and methods for their preparation | |
| CN1220486C (en) | resveratrol , piceid and its derivative and its preparation | |
| Hoskins et al. | Simple calix [n] arenes and calix [4] resorcinarenes as drug solubilizing agents | |
| WO2008031285A1 (en) | Pharmaceutical composition containing docetaxel-cyclodextrin inclusion complex and its preparing process | |
| Aghazadeh-Habashi et al. | High performance liquid chromatographic determination of glucosamine in rat plasma | |
| CN1167734C (en) | Inclusion compound of ginsenoside RG3 and hydroxypropyl-beta-cyclodextrin and its preparation and preparing process | |
| RU2316314C2 (en) | Method for production of block-copolymer-drug composite | |
| Pedotti et al. | Synthesis and physico-chemical characterization of a β-cyclodextrin conjugate for sustained release of Acyclovir | |
| CN112876398B (en) | Indole tricarbocyanine dye compound and preparation method and application thereof | |
| Zheng et al. | Inositol hexanicotinate self-micelle solid dispersion is an efficient drug delivery system in the mouse model of non-alcoholic fatty liver disease | |
| WO2010128243A1 (en) | Method for preparing polyphenol extracts from spinach leaves | |
| CN114225050B (en) | Preparation and application of ethinylestradiol cyclodextrin compound | |
| Yong et al. | The effect of β-cyclodextrin complexation on the bioavailability and hepatotoxicity of clotrimazole | |
| CN1883497A (en) | Ginsenoside Rh2 hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof | |
| CN109846865A (en) | A kind of curcumin preparation and preparation method thereof | |
| Amin Kreaz et al. | The influence of β-cyclodextrins on the solubility of furosemide | |
| Breda et al. | Determination of 3'-deamino-3'-[2 (S)-methoxy-4-morpholinyl] doxorubicin, a new morpholinyl anthracycline, in plasma by high-performance liquid chromatography with fluorescence detection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| 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 | ||
| ASS | Succession or assignment of patent right |
Owner name: SHENYANG WANJIA BIOTECHNOLOGY INSTITUTE CO., LTD. Free format text: FORMER OWNER: DONG YINGJIE Effective date: 20090717 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20090717 Address after: Liaoning Province in Dongling District of Shenyang City fengle Street No. 88, a zip code: 110015 Patentee after: Shenyang Wanjia Institute of Biotechnology Co.,Ltd. Address before: No. 6-1, Fang Qing Bei Road, Dongling District, Shenyang, Liaoning 1-51, zip code: 110015 Co-patentee before: Ai Li Patentee before: Dong Yingjie Effective date of registration: 20090717 Address after: No. 6-1, Fang Qing Bei Road, Dongling District, Shenyang, Liaoning 1-51, zip code: 110015 Co-patentee after: Ai Li Patentee after: Dong Yingjie Address before: No 58, Changqing street, Shenyang, Liaoning: 110015 Patentee before: Dong Yingjie |
|
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: BEIJING JIUJIU FANGYUAN HEALTH PRODUCTS DISTRIB Co.,Ltd. Assignor: Shenyang Wanjia Institute of Biotechnology Co.,Ltd. Contract record no.: 2012210000063 Denomination of invention: Inclusion compound of ginsenoside RG3 and hydroxypropyl-beta-cyclodextrin and its preparation and preparing process Granted publication date: 20040922 License type: Common License Open date: 20030129 Record date: 20120511 |
|
| ASS | Succession or assignment of patent right |
Owner name: LIAONING WANJIA PHARMACEUTICAL TECHNOLOGY CO., LTD Free format text: FORMER OWNER: SHENYANG WANJIA BIOTECHNOLOGY INSTITUTE CO., LTD. Effective date: 20131014 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 110015 SHENYANG, LIAONING PROVINCE TO: 117004 BENXI, LIAONING PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20131014 Address after: 117004 bio pharmaceutical industry park, Benxi Economic Development Zone, Liaoning Patentee after: LIAONING WANJIA MEDICAL TECHNOLOGY Co.,Ltd. Address before: 110015 Liaoning Province in Dongling District of Shenyang City fengle Street No. 88 Patentee before: Shenyang Wanjia Institute of Biotechnology Co.,Ltd. |
|
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20030129 Assignee: BEIJING JIUJIU FANGYUAN HEALTH PRODUCTS DISTRIB Co.,Ltd. Assignor: Shenyang Wanjia Institute of Biotechnology Co.,Ltd. Contract record no.: 2012210000063 Denomination of invention: Inclusion compound of ginsenoside RG3 and hydroxypropyl-beta-cyclodextrin and its preparation and preparing process Granted publication date: 20040922 License type: Common License Record date: 20120511 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20040922 Termination date: 20190702 |