CN102133244A - Preparation method of low-acid and high-quality ginkgo leaf extractive - Google Patents
Preparation method of low-acid and high-quality ginkgo leaf extractive Download PDFInfo
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Abstract
The invention discloses a preparation method of a low-acid and high-quality ginkgo leaf extractive, which comprises the steps of extraction, fine purification and separation and concentrated drying. In the ginkgo leaf extractive obtained in the method, the total content of flavones is up to over 65% (wherein a flavonoide content is up to over 35%), the total content of terpene lactone is up to over 10%, the content of 3,3'-dimethoxy-4,4'-dyhydroxy diphenylethene is up to over 0.05%, and the content of ginkgoic acid can be less than 2ppm. Compared with the prior art, in the invention, the content of the 3,3'-dimethoxy-4,4'-dyhydroxy diphenylethene is quantitatively controlled for the first time, the low-acid and high-quality ginkgo leaf extractive has high enrichment and extraction rate of active constituents, low content of the ginkgoic acid as a harmful constituent and has the characteristics that a production process meets the requirement of industrial large-scale production, and a process route is more reasonable.
Description
Technical field
The present invention relates to the preparation method of the high-quality Folium Ginkgo extract of a kind of low acid, this Folium Ginkgo extract can be used as the crude drug of diseases such as dizzy and coronary heart disease that treatment the blood stasis type thoracic obstruction and the slight cerebral arteriosclerosis of blood stasis type cause, angina pectoris, myocardial infarction, belongs to the Chinese drug preparation technique field.
Background technology
Cardiovascular and cerebrovascular disease occupies various causes of the death first place, has become the highest No.1 killer of the human dead cause of disease.According to statistics, at present China more than 60 years old population exceeded 300,000,000, the arriving of aged tendency of population makes the also corresponding rising of cardiovascular and cerebrovascular disease patient.Modern society impels the sickness rate of cardiovascular and cerebrovascular disease in 30 years old to 40 years old young and middle-aged people also constantly to rise from the pressure of aspects such as work, society, life simultaneously, and the age span of morbidity is in continuous expansion.At present, though the medicine of western medical treatment cardiovascular and cerebrovascular disease is more, owing to reasons such as side effect are big, clinical use is restricted.Gingko leaf preparation is effectively treated the medicine of cardiovascular and cerebrovascular disease as clinical safety, and extensive approval has been obtained in clinical market in the whole world.From the technical advance angle, gingko leaf preparation has experienced about 5 developmental stage so far, and promptly the first generation is dried Folium Ginkgo, pulverizes the crude drug in whole tabletting; The second filial generation is condensed into cream with Folium Ginkgo after with water extraction, oven dry, pelletizing press sheet then, but wherein main effective ingredient ginkgetin and bilobalide are not controlled; The third generation carries out qualitative control to main effective ingredient ginkgetin and bilobalide on the basis of the second filial generation, do not indicate but there is harmful components ginkgoic acid content; The 4th generation control effective ingredient ginkgetin is more than 24%, and bilobalide is more than 6%, and the harmful components ginkgoic acid is controlled at below the 10ppm; The 5th generation control effective ingredient total flavones is more than 44%, and flavonoid glycoside is more than 24%, and bilobalide is more than 6%, and the harmful components ginkgoic acid is controlled at below the 5ppm.Chinese Pharmacopoeia 2010 editions requires to contain in the Folium Ginkgo extract total flavonoids must not be less than 24%, contains total lactone and must not be less than 6%, and ginkgoic acid content is less than 10ppm; American Pharmacopeia is that to contain total flavonoids be 22～27% to this requirement, and containing total lactone is 5.4～12%, and ginkgoic acid content is less than 10ppm; Deutscher Arzneibucs is that total flavonoids is 22～27% to this requirement, and containing lactone is 5～7%, and ginkgoic acid content is less than 10ppm.This shows that the content of total flavonoids, total lactone and ginkgoic acid controlled well is the key factor of Folium Ginkgo extract quality.
The existing Technology of the Folium Ginkgo extract of having reported has microwave extraction method, supercritical extraction etc.Great majority are only paid close attention to the purification of extract in the prior art, pursue the high-load of effective ingredient, have ignored the content control that is harmful to into the composition ginkgoic acid, cause untoward reaction in clinical use easily.For head it off, there is the minority report to propose to increase active constituent content, reduce the Folium Ginkgo extract of harmful components content, but extraction process is loaded down with trivial details, the needs that also have are used noble fillers such as polydextran gel, can't realize industrialized great production.Secondly; effective ingredient only focuses on ginkgetin alcohol glycosides and terpene lactone at present; and bibliographical information stilbene constituents has effects such as antioxidation, blood fat reducing; cardiovascular is had good protective action, might be another big active component of Semen Ginkgo extrac treatment cardiovascular and cerebrovascular disease.And at present the document patent of all reports all control wherein 3,3 '-dimethoxy-4 ', 4 '-content of dihydroxy stilbene.
Summary of the invention
The preparation method that the purpose of this invention is to provide the high-quality Folium Ginkgo extract of a kind of low acid, the Folium Ginkgo extract that obtains by this extracting method, significantly improve the content of active component Ginkgo total flavones alcohol glycosides, total lactone, reduce the content of harmful components ginkgoic acid, to better meet the clinical needs of medicine; First the stilbene constituents in the Folium Ginkgo extract has been carried out quantitative control, with better control product quality.
The objective of the invention is to realize in the following manner:
The preparation method of the high-quality Folium Ginkgo extract of a kind of low acid, this method may further comprise the steps:
A) dry ginkgo leaf powder being broken to 20～30 mesh sieves, is that 65～85% alcohol heating reflux extract with mass percent concentration, filters, and filtrate is concentrated into thick paste;
B) add the water of 3～6 times of Folium Ginkgo weight in above-mentioned thick paste, stir evenly, 24～48h is left standstill in cold preservation, and is centrifugal, supernatant;
C) with the supernatant that makes, with the ratio of every gram resin adding 1.5～2.5ml supernatant, by the ion exchange column of hybrid resin composition, wash with water earlier, the reuse mass percent concentration is 55～70% ethanol elution, collects 55～70% ethanol elution, eluent is concentrated, get concentrated solution; Wherein, hybrid resin is that macroporous adsorbent resin and polyamide are formed according to 4: 1～9: 1 weight ratio; Preferred macroporous adsorbent resin and polyamide are formed according to 6: 1～9: 1 weight ratio.
D) add entry and low polar organic solvent as extractant in the gained concentrated solution, extract 2～3 times, organic layer discards, and water liquid concentrates, and gets concentrated solution; Dry concentrated solution gets Folium Ginkgo extract.
Described macroporous adsorbent resin is preferably DM130, AB-8 or D101 type; Described extractant is the water of 1～3 times of concentrated solution volume and 1～3 times low polar organic solvent, and wherein, low polar organic solvent is ether, chloroform, cyclohexane extraction or normal hexane, preferred cyclohexane extraction or normal hexane.Consumption is 3～4 times of column volumes when adopting water washing, 12～16 times of column volumes of consumption during ethanol elution, and elution speed is 20～30ml/min.Described dry concentrated solution mode is spray drying or vacuum drying.
Total flavones contains more than 65% and (contains the flavonol glycosides more than 35% in the Folium Ginkgo extract) in the prepared high-quality Folium Ginkgo extract of the present invention, total terpene lactone contains more than 10%, 3,3 '-dimethoxy-4 ', 4 '-dihydroxy stilbene content reaches more than 0.05%, and ginkgoic acid content is lower than 2ppm.The number of times of reflux, extract, can be 1～3 time in step a), and each extraction time is 1～2 hour, and each ethanol consumption is 6～14 times of Folium Ginkgo dry weight.Preferred reflux, extract, 3 times, each extraction time is 1～2 hour, three ethanol amount ranges are respectively 12～14 times (for the first time) of Folium Ginkgo dry weight, 10～12 times (for the second time), 6～8 times (for the third time).Extracting the concentrated thick paste relative density in the time of 60 ℃ that obtains in back is 1.15～1.25." % " of above-mentioned Folium Ginkgo extract composition indication is the quality percentage composition.
The main screening process of key process parameter is as follows:
Test 1, investigated the effect of dissimilar enriching and purifying macroporous resin Folium Ginkgo extract.
Get the dry Folium Ginkgo of 7 parts of 1kg, pulverize separately is crossed 20～30 mesh sieves, extract three times with 75% alcohol heating reflux, each time all is respectively 1.5 hours, three times the ethanol amount ranges is: be respectively 14 times of Folium Ginkgo dry weight, and 10 times, 8 times, extracting solution merges, filter, relative density is behind 1.15～1.25 the thick paste, to add 3 times of water gagings of dry Folium Ginkgo when being evaporated to 60 ℃, fully stir evenly, after Cool Room 4 cold preservation is left standstill 48 hours, centrifugal, the macroporous resin column that supernatant is different excessively respectively, first distilled water wash with 4 times of column volumes, again respectively with 6 times of column volume mass percent concentrations be the ethanol of 55% ethanol and 8 times of column volumes 70% by 20ml/min speed eluting, merge eluent, eluent concentrates, spray drying, promptly.
The result is as shown in table 1:
Table 1
By contrast test, find that different macroporous adsorbent resins there are differences the purification effect of ginkgetin and lactone, best with D101, AB-8 and DM130 type effect, but the content of harmful components ginkgoic acid is all higher, also need be further purified.Test 2, investigation add polyamide and remove ginkgoic acid in macroporous adsorbent resin: extract purification step with test 1, only change the hybrid resin post that purification uses, measure the content of ginkgoic acid in the extract according to 2010 editions Chinese Pharmacopoeia methods according to different proportion dress post.The changes of contents result of ginkgoic acid is as shown in table 2 behind the hybrid resin column purification of different proportion:
Table 2
Found that: macroporous adsorbent resin and polyamide proportion of composing must reach certain numerical value could be in the enriching and purifying effective ingredient, removal harmful components ginkgoic acid as much as possible, when both form part by weight between 4: 1～9: 1 when (preferably both form part by weight between 6: 1～9: 1), the content of ginkgoic acid is reduced to about 10ppm, reach requirement, and other content of effective there is not significant change.But ginkgoic acid content is still higher, needs to explore to be further purified.
Test 3, resin elution concentrated solution adopt low polar organic solvent extraction, screen different organic solvents: extract purification step with test 1, the hybrid resin that purification uses is adorned post as DM130 macroporous resin and polyamide according to weight ratio at 4: 1, the eluent that obtains concentrates, use the water extraction of 2 times of 2 times of low polar organic solvents of concentrated solution volume shown in the table 3 and concentrated solution volumes more respectively, organic layer discards, and water concentrates, spray drying, promptly.Measure the content of ginkgoic acid in the extract according to 2010 editions Chinese Pharmacopoeias.The result is as shown in table 3:
Table 3
The concentrated solution of hybrid resin eluent through low polar organic solvent extraction, can guarantee that ginkgoic acid content significantly reduces again, and particularly cyclohexane extraction and normal hexane are purified to ginkgoic acid content below the 2ppm.
Beneficial effect of the present invention compared with the prior art: with respect to prior art, adopt the first macroporous adsorbent resin technology of polyamide more mostly, troublesome poeration can not guarantee whether the content of ginkgoic acid in the final products is minimum simultaneously.Extraction process step of the present invention is few, and does not adopt the big organic reagent of toxicity, and prepared extract is easier to reach the clinical requirement that will use.First to 3,3 '-dimethoxy-4 ', 4 '-dihydroxy stilbene content carried out quantitative control; Harmful components ginkgoic acid content can be controlled in below the 2ppm, effective ingredient enrichment extraction ratio height; Have processes such as extraction, remove impurity, purification, extraction, column chromatography enriching and purifying and meet the big production requirement of industry, process route is advantage of reasonable more.The high-quality Folium Ginkgo extract of low acid of the present invention can be used as the quality raw materials source of dissimilar gingko leaf preparations.
The specific embodiment
With specific embodiment the present invention is elaborated below, involved method is the technological means that those skilled in the art can grasp and use, but the invention is not restricted to described embodiment.
Following example is raw material with the Folium Ginkgo.Plucked when autumn, Folium Ginkgo was still green, remove impurity, dry in the shade.Total flavonoids content is more than 0.85% in the Folium Ginkgo of selecting for use, and total terpene lactone contents is more than 0.25%.
Embodiment 1:
Dry Folium Ginkgo 1kg, be crushed to 20 mesh sieves, with mass percent is 70% alcohol reflux three times, adds 14 times of amount alcohol of dry Folium Ginkgo weight for the first time, extracts 1 hour, second and third time adds 12,8 times of amount alcohol of dry Folium Ginkgo weight respectively, all extracted 1.5 hours, merge extractive liquid, filters, decompression recycling ethanol is concentrated into thick paste (60 ℃ time relative density 1.15).Add the water of 3 times of amounts of dry Folium Ginkgo weight, fully stir evenly, leave standstill 48 hours in Cool Room 4, centrifugal, get supernatant.With the ratio of every gram resin adding 2ml supernatant, by the ion exchange column of being made up of hybrid resin (wherein macroporous adsorbent resin DM130 is 9: 1 with the dress post ratio of polyamide), dress post blade diameter length ratio is 1: 6.Earlier with 4 times of column volume distilled water washs, more respectively with 6 times of column volume mass percent concentrations be the ethanol of 55% ethanol and 8 times of column volumes 70% by 20ml/min speed eluting, the merging eluent, decompression recycling ethanol must concentrated solution.Add the water of 3 times of concentrated solution volumes and the cyclohexane extraction of 1 times of volume, extract 2 times, organic layer discards, and water concentrating under reduced pressure, concentrated solution be in vacuum drying below 60 ℃, must about 12g Folium Ginkgo extract, and Folium Ginkgo extract dry powder yield is 1.2%.According to 2010 editions Folium Ginkgo extract content assaying methods of Chinese Pharmacopoeia, recording general flavone content is: 66.5% (wherein flavonol glycosides content is 45.1%), the content of total lactone is 11.5%, 3,3 '-dimethoxy-4 ', 4 '-content of dihydroxy stilbene is 0.07%, the content of ginkgoic acid is 2ppm.
Embodiment 2:
Dry Folium Ginkgo 5kg, be crushed to 20 mesh sieves, with mass percent is 80% alcohol reflux three times, adds 12 times of amount alcohol of dry Folium Ginkgo weight for the first time, extracts 2 hours, 10,6 times of amounts of second and third time difference, all extracted 1.5 hours, merge extractive liquid, filters, decompression recycling ethanol is concentrated into thick paste (60 ℃ time relative density 1.17).Add the water of 5 times of leaf weight, fully stir evenly, leave standstill 24 hours in freezer, centrifugal, get supernatant.Add the ratio of 2.5ml supernatant with every gram resin, by the ion exchange column of having handled well of being made up of hybrid resin (wherein macroporous adsorbent resin AB-8 is 8: 1 with the dress post ratio of polyamide), adorning the post blade diameter length ratio is 1: 7.Earlier with 4 times of column volume distilled water washs, more respectively with 6 times of column volume mass percent concentrations be the ethanol of 55% ethanol and 8 times of column volumes 65% with 30ml/min speed eluting, the merging eluent, decompression recycling ethanol must concentrated solution.Add the water of 2 times of concentrated solution volumes and the ether of 1 times of volume, extract 3 times, organic layer discards, the water concentrating under reduced pressure, and the concentrated solution spray drying must about 51g Folium Ginkgo extract, and Folium Ginkgo extract dry powder yield is 1.02%.According to 2010 editions Folium Ginkgo extract content assaying methods of Chinese Pharmacopoeia, recording general flavone content is: 66.8% (wherein flavonol glycosides content is 44.6%), the content of total lactone is 11.8%, 3,3 '-dimethoxy-4 ', 4 '-content of dihydroxy stilbene is 0.06%, the content of ginkgoic acid is 5ppm.
Embodiment 3:
Dry Folium Ginkgo 50kg, pulverized 20 mesh sieves, with mass percent is 85% alcohol reflux three times, adds 13 times of amount alcohol of dry Folium Ginkgo weight for the first time, extracts 1.5 hours, 11,7 times of amounts of second and third time difference, all extracted 1 hour, merge extractive liquid, filters, decompression recycling ethanol is concentrated into thick paste (60 ℃ time relative density 1.20).Add the water of 5 times of leaf weight, fully stir evenly, leave standstill 48 hours in freezer, centrifugal, get supernatant.Add the ratio of 2ml supernatant with every gram resin, by the ion exchange column of having handled well of being made up of hybrid resin (wherein macroporous adsorbent resin D101 is 9: 1 with the dress post ratio of polyamide), adorning the post blade diameter length ratio is 1: 5.Earlier with 3 times of column volume distilled water washs, more respectively with 6 times of column volume mass percent concentrations be the ethanol of 55% ethanol and 8 times of column volumes 65% with 25ml/min speed eluting, the merging eluent, decompression recycling ethanol must concentrated solution.Add the water of 2 times of concentrated solution volumes and the normal hexane of 2 times of volumes, extract 2 times, organic layer discards, the water concentrating under reduced pressure, and the concentrated solution spray drying must about 580g Folium Ginkgo extract, and the dry powder yield is 1.16%.According to 2010 editions Folium Ginkgo extract content assaying methods of Chinese Pharmacopoeia, recording general flavone content is: 67.0% (wherein flavonol glycosides content is 43.5%), the content of total lactone is 11.3%, 3,3 '-dimethoxy-4 ', 4 '-content of dihydroxy stilbene is 0.07%, the content of ginkgoic acid is 1ppm.
Embodiment 4:
Dry Folium Ginkgo 10kg, be crushed to 30 mesh sieves, with mass percent 65% alcohol reflux three times, add 14 times of amount alcohol of dry Folium Ginkgo weight for the first time, extracted 2 hours, 10,6 times of amounts of second and third time difference, all extracted 1 hour, merge extractive liquid, filters, decompression recycling ethanol is concentrated into thick paste (60 ℃ time relative density 1.25).Add the water of 6 times of leaf weight, fully stir evenly, leave standstill 36 hours in Cool Room 4, centrifugal, get supernatant.Add the ratio of 2.5ml supernatant with every gram resin, by the ion exchange column of having handled well of being made up of hybrid resin (wherein macroporous adsorbent resin DM130 is 4: 1 with the dress post ratio of polyamide), adorning the post blade diameter length ratio is 1: 8.Earlier with 4 times of column volume distilled water washs, more respectively with 6 times of column volume mass percent concentrations be the ethanol of 55% ethanol and 8 times of column volumes 70% with 20ml/min speed eluting, the merging eluent, decompression recycling ethanol must concentrated solution.Add the water of 1 times of concentrated solution volume and the chloroform of 3 times of volumes, extract 3 times, organic layer discards, and water concentrating under reduced pressure, concentrated solution be in vacuum drying below 60 ℃, must about 106g Folium Ginkgo extract, and the dry powder yield is 1.06%.According to 2010 editions Folium Ginkgo extract content assaying methods of Chinese Pharmacopoeia, recording general flavone content is: 66.2% (wherein flavonol glycosides content is 44.7%), the content of total lactone is 10.9%, 3,3 '-dimethoxy-4 ', 4 '-content of dihydroxy stilbene is 0.06%, the content of ginkgoic acid is 5ppm.
Embodiment 5:
Dry Folium Ginkgo 10kg, be crushed to 20 mesh sieves, with mass percent 65% alcohol reflux three times, add 12 times of amount alcohol of dry Folium Ginkgo weight for the first time, extracted 1.5 hours, 10,6 times of amounts of second and third time difference, all extracted 1 hour, merge extractive liquid, filters, decompression recycling ethanol is concentrated into thick paste (60 ℃ time relative density 1.25).Add the water of 4 times of leaf weight, fully stir evenly, leave standstill 36 hours in Cool Room 4, centrifugal, get supernatant.Add the ratio of 2.5ml supernatant with every gram resin, by the ion exchange column of having handled well of being made up of hybrid resin (wherein macroporous adsorbent resin DM130 is 7: 1 with the dress post ratio of polyamide), adorning the post blade diameter length ratio is 1: 8.Earlier with 3 times of column volume distilled water washs, more respectively with 7 times of column volume mass percent concentrations be the ethanol of 55% ethanol and 9 times of column volumes 70% with 20ml/min speed eluting, the merging eluent, decompression recycling ethanol must concentrated solution.Add the water of 1 times of concentrated solution volume and the cyclohexane extraction of 3 times of volumes, extract 3 times, organic layer discards, and water concentrating under reduced pressure, concentrated solution be in vacuum drying below 60 ℃, must about 108g Folium Ginkgo extract, and the dry powder yield is 1.08%.According to 2010 editions Folium Ginkgo extract content assaying methods of Chinese Pharmacopoeia, recording general flavone content is: 67.0% (wherein flavonol glycosides content is 44.9%), the content of total lactone is 11.5%, 3,3 '-dimethoxy-4 ', 4 '-content of dihydroxy stilbene is 0.07%, the content of ginkgoic acid is 1ppm.
Embodiment 6:
Dry Folium Ginkgo 5kg, be crushed to 30 mesh sieves, with mass percent is 75% alcohol reflux secondary, adds 12 times of amount alcohol of dry Folium Ginkgo weight for the first time, extracts 2 hours, 10 times of amounts are pure for the second time, extracted 1.5 hours, merge extractive liquid, filters, decompression recycling ethanol is concentrated into thick paste (60 ℃ time relative density 1.17).Add the water of 3 times of leaf weight, fully stir evenly, leave standstill 24 hours in freezer, centrifugal, get supernatant.Add the ratio of 2ml supernatant with every gram resin, by the ion exchange column of having handled well of being made up of hybrid resin (wherein macroporous adsorbent resin AB-8 is 4: 1 with the dress post ratio of polyamide), adorning the post blade diameter length ratio is 1: 6.Earlier heat up in a steamer water washing with steaming 4 times of column volumes, more respectively with 6 times of column volume mass percent concentrations be the ethanol of 55% ethanol and 8 times of column volumes 70% with 30ml/min speed eluting, the merging eluent, decompression recycling ethanol must concentrated solution.Add the water of 2 times of concentrated solution volumes and the ether of 1 times of volume, extract 3 times, organic layer discards, the water concentrating under reduced pressure, and the concentrated solution spray drying must about 51.5g Folium Ginkgo extract, and Folium Ginkgo extract dry powder yield is 1.03%.According to 2010 editions Folium Ginkgo extract content assaying methods of Chinese Pharmacopoeia, recording general flavone content is: 66.6% (wherein flavonol glycosides content is 42.5%), the content of total lactone is 10.9%, 3,3 '-dimethoxy-4 ', 4 '-content of dihydroxy stilbene is 0.06%, the content of ginkgoic acid is 5ppm.
Embodiment 7:
Dry Folium Ginkgo 50kg, be crushed to 20 mesh sieves, with mass percent is 65% alcohol reflux three times, adds 14 times of amount alcohol of dry Folium Ginkgo weight for the first time, extracts 1.5 hours, 10,8 times of amounts of second and third time difference, all extracted 1 hour, merge extractive liquid, filters, decompression recycling ethanol is concentrated into thick paste (60 ℃ time relative density 1.25).Add the water of 3 times of leaf weight, fully stir evenly, leave standstill 48 hours in freezer, centrifugal, get supernatant.Add the ratio of 1.5ml supernatant with every gram resin, by the ion exchange column of having handled well of being made up of hybrid resin (wherein macroporous adsorbent resin D101 is 4: 1 with the dress post ratio of polyamide), adorning the post blade diameter length ratio is 1: 7.Earlier with 4 times of column volume distilled water washs, more respectively with 5 times of column volume mass percent concentrations be the ethanol of 55% ethanol and 7 times of column volumes 70% with 25ml/min speed eluting, the merging eluent, decompression recycling ethanol must concentrated solution.Add the water of 2 times of concentrated solution volumes and the cyclohexane extraction of 2 times of volumes, extract 3 times, organic layer discards, the water concentrating under reduced pressure, and concentrated solution reduced vacuum drying must about 600g Folium Ginkgo extract, and the dry powder yield is 1.2%.According to 2010 editions Folium Ginkgo extract content assaying methods of Chinese Pharmacopoeia, recording general flavone content is: 66.9% (wherein flavonol glycosides content is 43.7%), the content of total lactone is 11.1%, 3,3 '-dimethoxy-4 ', 4 '-content of dihydroxy stilbene is 0.06%, the content of ginkgoic acid is 1ppm.
Claims (9)
1. the preparation method of a Folium Ginkgo extract is characterized in that this method may further comprise the steps:
A) dry ginkgo leaf powder being broken to 20～30 mesh sieves, is the alcohol heating reflux extraction of 65-85% with mass percent concentration, filters, and filtrate is concentrated into thick paste;
B) add the water of 3～6 times of Folium Ginkgo weight in above-mentioned thick paste, 24～48h is left standstill in cold preservation, and is centrifugal, supernatant;
C) with the supernatant that makes, with the ratio of every gram resin adding 1.5～2.5ml supernatant, by the ion exchange column of hybrid resin composition, wash with water earlier, the reuse mass percent concentration is 55～70% ethanol elution, collects 55～70% ethanol elution, eluent is concentrated, get concentrated solution; Wherein, hybrid resin is that macroporous adsorbent resin and polyamide are formed according to 4: 1～9: 1 weight ratio;
D) add entry and low polar organic solvent as extractant in the gained concentrated solution, extract 2～3 times, organic layer discards, and water liquid concentrates, and gets concentrated solution; Dry concentrated solution gets Folium Ginkgo extract.
2. preparation method according to claim 1 is characterized in that the relative density in the time of 60 ℃ of the thick paste described in the step a) is 1.15～1.25.
3. preparation method according to claim 1 is characterized in that macroporous adsorbent resin is DM130, AB-8 or D101 type in the step c).
4. preparation method according to claim 1 is characterized in that hybrid resin is that macroporous adsorbent resin and polyamide are formed according to 6: 1～9: 1 weight ratio in the step c).
5. preparation method according to claim 1 is characterized in that the extractant described in the step d) is the water of 1～3 times of concentrated solution volume and 1～3 times low polar organic solvent, and wherein, low polar organic solvent is ether, chloroform, cyclohexane extraction or normal hexane.
6. preparation method according to claim 5 is characterized in that the low polar organic solvent described in the step d) is cyclohexane extraction or normal hexane.
7. preparation method according to claim 1 is characterized in that described drying is spray drying or vacuum drying.
8. preparation method according to claim 1 is characterized in that total flavones contains more than 65% in the prepared Folium Ginkgo extract, and total terpene lactone contents contains more than 10%, 3,3 '-dimethoxy-4 ', 4 '-dihydroxy stilbene content reaches more than 0.05%, and ginkgoic acid content is lower than 2ppm.
9. preparation method according to claim 1 is characterized in that containing the flavonol glycosides more than 35% in Folium Ginkgo extract.
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| CN107753529A (en) * | 2017-11-09 | 2018-03-06 | 重庆科瑞南海制药有限责任公司 | A kind of preparation method of ginkgo biloba p.e |
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| CN102283870A (en) * | 2011-09-09 | 2011-12-21 | 黑龙江省珍宝岛制药有限公司 | High-purity folium ginkgo composition, preparation including same and preparation method thereof |
| CN102283870B (en) * | 2011-09-09 | 2014-04-16 | 黑龙江珍宝岛药业股份有限公司 | High-purity folium ginkgo composition, preparation including same and preparation method thereof |
| CN102614229A (en) * | 2012-04-25 | 2012-08-01 | 江苏神龙药业有限公司 | Method for removing ginkgolic acid from ginkgo biloba extract |
| CN102614229B (en) * | 2012-04-25 | 2015-04-08 | 江苏神龙药业有限公司 | Method for removing ginkgolic acid from ginkgo biloba extract |
| CN106176838A (en) * | 2016-07-18 | 2016-12-07 | 湖南绿蔓生物科技股份有限公司 | A kind of production method of Folium Ginkgo extract |
| CN106176838B (en) * | 2016-07-18 | 2019-10-25 | 湖南绿蔓生物科技股份有限公司 | A kind of production method of ginkgo biloba p.e |
| CN107753529A (en) * | 2017-11-09 | 2018-03-06 | 重庆科瑞南海制药有限责任公司 | A kind of preparation method of ginkgo biloba p.e |
| CN107753529B (en) * | 2017-11-09 | 2020-12-11 | 重庆科瑞南海制药有限责任公司 | Preparation method of ginkgo leaf extract |
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| CN102133244B (en) | 2013-03-27 |
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