CN102627680B - Ginsenoside Rg1 compound and pharmaceutical composition containing the same - Google Patents
Ginsenoside Rg1 compound and pharmaceutical composition containing the same Download PDFInfo
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Abstract
The invention relates to a ginsenoside Rg1 and a preparation method thereof. The ginsenoside Rg1 is a crystal, and results of X-ray powder diffraction of the ginsenoside Rg1 measured by Cu-Kalpha ray show that characteristic peaks appear at 2theta of 9.91DEG, 12.37DEG, 13.60DEG, 15.20DEG, 16.65DEG, 20.20DEG, 22.21DEG, 22.70DEG, 23.35DEG, 24.15DEG and 25.67DEG. The ginsenoside Rg1 crystal provided in the invention has a good stability and an excellent medicine formation base. The invention also relates to a pharmaceutical composition containing the ginsenoside Rg1; and the pharmaceutical composition is a Xuesaitong effervescent tablet and a Xuesaitong dispersing tablet.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of ginsenoside Rg1, ginsenoside Rg1's preparation method and contain ginsenoside Rg1's pharmaceutical composition.
Background technology
The ginsenoside Rg1 has treatment cardiovascular and cerebrovascular diseases, antithrombotic, anti-fibrosis, treatment senile dementia, improves immunizing power, various tumours is had auxiliary therapeutic action etc., has significantly and widely pharmacologically active, and the patent medicine basis is good.But, ginsenoside Rg1's poor stability, its glycosidic bond is easy fracture under acid, alkaline condition.
The efficient part Radix Notoginseng total arasaponins that the main component of XUESAITONG is extracted for the araliaceae ginseng plant pseudo-ginseng, the main component of Radix Notoginseng total arasaponins is ginsenoside Rg1, ginsenoside Rb1 and arasaponin R1, and 2010 editions " Chinese pharmacopoeia assigns to control its quality take the content of ginsenoside Rg1, ginsenoside Rb1 and arasaponin R1 as index one-tenth.XUESAITONG table sugar garment piece is because prolonged disintegration, drug-eluting is slower, oral administration biaavailability is low, also be unfavorable for being difficult to swallow the old man of solid preparation, children and be difficult to the swallower and take, effervescent tablet is used more a kind of quick-release novel form as Recent study, the difference of it and conventional tablet, just be that it also contains gas-producing disintegrant, after effervescent tablet is put into drinking-water, under the effect of gas-producing disintegrant, at once produce the great amount of carbon dioxide bubble, make the rapid disintegration of tablet and thawing, sometimes the bubble that disintegration produces also can make tablet up and down rolling in water, accelerates its disintegration and thawing.The carbonic acid gas that produces during disintegration of tablet is partially dissolved in the drinking-water, making drinking-water that aesthetic feeling as the carbonated drink be arranged when drinking in the entrance.Because effervescent tablet has added alkali and organic acid in the process of preparation, the poor stability of effervescent tablet, the long-time storage, activeconstituents is ginsenoside Rg1's content particularly, and its related substances increases, and has increased the risk of patient safety medication.
Chinese patent CN102086223A discloses a kind of ginsenoside Rg1's preparation method: extract the total saponins that obtains from pseudo-ginseng, ginseng, Radix Panacis Quinquefolii or gynostemma pentaphylla, total saponins is dissolved in water, filters, and filtrate is by nonpolar or low-pole macroporous resin, washing, elutriant discards, 25%～35% ethanol elution, elutriant discards, use again 40%～50% ethanol elution, collect elutriant, concentrate drying, dry product adds organic solvent extraction, extracting solution filters, and residue is dry, namely gets the ginsenoside Rg1.The method has the characteristics such as extraction yield is high, the organic solvent use is few.
Chinese patent CN1723971A discloses a kind of Effervesce tablet for dredging thrombosis and preparation method thereof, this Effervesce tablet for dredging thrombosis comprises 40～60 parts of Radix Notoginseng total arasaponinss, 200～225 parts of lactose, 6～10 parts of Steviosins, 45～60 parts in tartrate, 40～55 parts of sodium bicarbonates, 20～30 parts of polyethylene glycol 6000s, 1～3 part of Magnesium Stearate.Remove in proportion Radix Notoginseng total arasaponins, lactose, Steviosin, tartrate, mix, be ground into fine powder, with ethanol softwood processed, granulate, drying, whole grain; In addition taking polyethylene glycol 6000 meltings add sodium bicarbonate, stir, and are ground into fine powder after the cooling, sieve, and with above-mentioned particle, Magnesium Stearate mixing, compressing tablet and get final product.
Chinese patent CN1839861A also discloses a kind of Effervesce tablet for dredging thrombosis and preparation method thereof, and every contains Radix Notoginseng total arasaponins 25～100mg, lactose 100～415mg, Steviosin 5～20mg, tartrate 28～120mg, sodium bicarbonate 26～110mg, polyethylene glycol 6000 12～50mg.Radix Notoginseng total arasaponins adds lactose, Steviosin, tartrate, pulverizes, and mixes, and with ethanol softwood processed, crosses the wet grain of sieve series, drying, whole grain; In addition taking polyethylene glycol 6000 meltings add sodium bicarbonate, stir, and pulverize after the cooling, sieve, and with above-mentioned particle, Magnesium Stearate mixing, compressing tablet and get final product.
At present, ginsenoside Rg1 of the prior art, Effervesce tablet for dredging thrombosis and Xuesaitong dispersible tablet all do not address the above problem.Therefore, develop a kind of ginsenoside Rg1 of good stability, the Effervesce tablet for dredging thrombosis that contains this ginsenoside Rg1 and dispersible tablet for clinical very necessary.
Summary of the invention
The object of the present invention is to provide a kind of ginsenoside Rg1 of new crystal, described ginsenoside Rg1 has better stability.
The second purpose of the present invention is to provide a kind of above-mentioned ginsenoside Rg1's preparation method.
The 3rd purpose of the present invention is to provide a kind of pharmaceutical composition that contains above-mentioned ginsenoside Rg1.
The 4th purpose of the present invention is to provide a kind of preparation method who contains above-mentioned ginsenoside Rg1's Radix Notoginseng total arasaponins.
For realizing goal of the invention of the present invention, adopt following technical scheme:
The ginsenoside Rg1 of a kind of formula I, described ginsenoside Rg1 is crystal, and the X-ray powder diffraction that described ginsenoside Rg1 uses the Cu-K alpha-ray to measure is 9.91 °, 12.37 °, 13.60 °, 15.02 °, 16.65 °, 20.20 °, 22.21 °, 22.70 °, 23.35 °, 24.15 °, 25.67 ° at 2 θ and locates to show characteristic peak;
Formula I.
The present inventor passes through experiment repeatedly, prepared a kind of ginsenoside Rg1 of new crystal, the fusing point of described ginsenoside Rg1's crystal is 203～205 ℃, slightly higher than prior art, have higher lattice energy, stability experiment shows, compared with prior art, the stability of ginsenoside Rg1's crystal provided by the invention is better, and the patent medicine basis is good.
Described ginsenoside Rg1's preparation method comprises: ginsenoside Rg1's crude product is dissolved in 45～55 ℃ of acetone/methanol mixing solutionss, wherein acetone and methyl alcohol are made into mixing solutions with 1: 3～4 volume ratio, regulate pH to 7～8 with triethylamine, add again gac, the constant temperature whip attachment, filter the decarburization degerming, speed cooling and while with 0.5～1.0 ℃/min slowly add ether, the consumption of described ether is 3～4 times of the volumes of acetone/methanol mixing solutions, be cooled to 0～5 ℃, filter, drying under reduced pressure obtains the white micro-crystals powder.
Same compound, different crystal formations cause inner solid-state structure different, cause its lattice energy different, and the higher then constraint to compound molecule of lattice energy is larger, and crystalline structure is more stable, and namely this compound is more stable.The contriver carries out recrystallization take ginsenoside Rg1's crude product as raw material, by experiment repeatedly, finally comprising solvent by change, temperature, crystallization rate, under the crystallization conditions such as anti-solvent, prepare a kind of ginsenoside Rg1 of new crystal, the X-ray powder diffraction that described ginsenoside Rg1's crystal uses the Cu-K alpha-ray to measure is 9.91 ° at 2 θ, 12.37 °, 13.60 °, 15.02 °, 16.65 °, 20.20 °, 22.21 °, 22.70 °, 23.35 °, 24.15 °, 25.67 ° show characteristic peak, its fusing point is 203～205 ℃, compared with prior art, the fusing point of ginsenoside Rg1's crystal of preparation of the present invention is slightly high, its lattice energy is also relatively high, and crystalline structure is highly stable.
Among the above-mentioned preparation method, per 25～35mg ginsenoside Rg1 dissolving crude product is in 1ml acetone/methanol mixing solutions.
Among the above-mentioned preparation method, the particle diameter of described white micro-crystals powder is 75～180 μ m.
In addition, the present invention also provides a kind of medicinal compositions, and described medicinal compositions comprises a kind of Radix Notoginseng total arasaponins that contains above-mentioned ginsenoside Rg1.
Preferably, described medicinal compositions is Effervesce tablet for dredging thrombosis or Xuesaitong dispersible tablet.
In weight part, described Effervesce tablet for dredging thrombosis comprises 45～55 parts of Radix Notoginseng total arasaponinss, 70～85 parts in tartrate, 15～25 parts of 75～85 parts of polyvinylpyrrolidones of 35～45 parts of lactose of 110～135 parts of sodium starch glycolatees of sodium bicarbonate, 5～6 parts of Steviosins, 3～4 parts of polyethylene glycol 6000s.
Preferably, in weight part, described Effervesce tablet for dredging thrombosis comprises 50 parts of Radix Notoginseng total arasaponinss, 80 parts in tartrate, 120 parts of sodium bicarbonates, 40 parts of sodium starch glycolatees, 80 parts of lactose, 20 parts of polyvinylpyrrolidones, 6 parts of Steviosins, 4 parts of polyethylene glycol 6000s.
In weight part, described Xuesaitong dispersible tablet comprises 45～55 parts of Radix Notoginseng total arasaponinss, 25～35 parts of cross-linked polyvinylpyrrolidones, 12～18 parts of low-substituted hydroxypropyl celluloses, 170～190 parts of Microcrystalline Celluloses, 1～3 part of Magnesium Stearate, 10 parts of sodium starch glycolatees.
Preferably, in weight part, described Xuesaitong dispersible tablet comprises 50 parts of Radix Notoginseng total arasaponinss, 30 parts of cross-linked polyvinylpyrrolidones, 15 parts of low-substituted hydroxypropyl celluloses, 180 parts of Microcrystalline Celluloses, 1 part of Magnesium Stearate, 10 parts of sodium starch glycolatees.
In addition, the contriver has also carried out stability experiment to Effervesce tablet for dredging thrombosis provided by the invention and Xuesaitong dispersible tablet, its result shows, Effervesce tablet for dredging thrombosis provided by the invention has shown extraordinary stability in accelerating experiment and long-term experiment, long-time storage foreign matter content is low, clinical safe and reliable, quality controllable.
Among the present invention, the preparation method of described Radix Notoginseng total arasaponins may further comprise the steps:
(1) gets the Radix Notoginseng total arasaponins bulk drug of recipe quantity, be dissolved in the methyl alcohol filtering with microporous membrane fully, upper macroporous adsorbent resin, ethanolic soln gradient elution with 60～80%, the component that will contain the ginsenoside Rg1 is collected separately and drying under reduced pressure, other component is merged collect;
(2) dried ginsenoside Rg1's crude product is dissolved in 45～55 ℃ of acetone/methanol mixing solutionss, wherein acetone and methyl alcohol are made into mixing solutions with 1: 3～4 volume ratio, regulate pH to 7～8 with triethylamine, add again gac, the constant temperature whip attachment, filter the decarburization degerming, speed cooling and while with 0.5～1.0 ℃/min slowly add ether, the consumption of described ether is 3～4 times of the volumes of acetone/methanol mixing solutions, be cooled to 0～5 ℃, filter, drying under reduced pressure obtains the white micro-crystals powder;
(3) add gac to merging in other component of collecting, whip attachment is filtered the decarburization degerming, and drying under reduced pressure obtains white powder;
(4) white powder that the white micro-crystals powder that step (2) is obtained and step (3) obtain mixes, and namely gets Radix Notoginseng total arasaponins.
Among the preparation method of above-mentioned Radix Notoginseng total arasaponins, in the described step (1), the consumption of Radix Notoginseng total arasaponins bulk drug and methyl alcohol is dissolved in 1ml methyl alcohol by per 20～30mg Radix Notoginseng total arasaponins bulk drug.
Among the preparation method of above-mentioned Radix Notoginseng total arasaponins, in the described step (1), also add the sodium-chlor of 3～5%mg/ml in the methyl alcohol.
Among the preparation method of above-mentioned Radix Notoginseng total arasaponins, in the described step (1), the model of macroporous adsorbent resin is D101, and elution flow rate is 0.5～1ml/min; Described elution flow rate is preferably 0.6ml/min.
Among the preparation method of above-mentioned Radix Notoginseng total arasaponins, in the described step (1), adopt 70% ethanolic soln gradient elution.
Among the preparation method of above-mentioned Radix Notoginseng total arasaponins, in the described step (2), described acetone and methyl alcohol are made into mixing solutions with 1: 3 volume ratio
The kind of the type of macroporous adsorbent resin, the concentration of loading, eluent and elution flow rate all are the important factors that affects fractionation by adsorption.The present invention preferably adopts the D101 macroporous adsorbent resin, and adds 3～5% sodium-chlor in loading solution, can not only accelerate resin to ginsenoside Rg1's rate of adsorption, and loading capacity increases obviously.The present invention is controlled at 20～30mg/ml with the loading strength of solution, and the adsorptive capacity of macroporous adsorbent resin is larger.In addition, when gradient elution, the excessive and too small weak effect that separates of all can causing of elution flow rate does not reach the purpose of separation, and the present invention determines that elution flow rate is 0.5～1ml/min, separation effective, and best elution flow rate is 0.6ml/min.
Described Effervesce tablet for dredging thrombosis can be with reference to the method preparation of any Effervesce tablet for dredging thrombosis of prior art, and preferred for this invention is:
(1) get Radix Notoginseng total arasaponins provided by the invention, tartrate, sodium bicarbonate, sodium starch glycolate, lactose and the polyvinylpyrrolidone of recipe quantity, mixing with 95～98% ethanolic solns softwood processed, is crossed 20 orders and is granulated;
(2) with behind the particle drying, add again Steviosin, sodium starch glycolate and the polyethylene glycol 6000 of recipe quantity, mixing, compacting is in blocks, and get final product.
Described Xuesaitong dispersible tablet can be with reference to the method preparation of any Xuesaitong dispersible tablet of prior art, and preferred for this invention is:
(1) get Radix Notoginseng total arasaponins, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, the Microcrystalline Cellulose of recipe quantity, mixing is that wetting agent is granulated with 95% ethanol, 60-65 ℃ of drying, whole grain;
(2) add again sodium starch glycolate, the Magnesium Stearate of recipe quantity, always mixed 28～35 minutes;
(3) after the passed examination, compressing tablet, packing.
Compared with prior art, ginsenoside Rg1 provided by the invention and pharmaceutical composition thereof have following advantage:
(1) ginsenoside Rg1's of the present invention stability is better, and the patent medicine basis is good.
(2) the pharmaceutical composition good stability that contains the ginsenoside Rg1 of the present invention is placed its related substances less, quality controllable for a long time;
(3) ginsenoside Rg1's of containing of the present invention pharmaceutical composition has improved patient's drug safety greatly.
Description of drawings
Fig. 1 is the X-RD spectrogram of ginsenoside Rg1's crystal of embodiment 1 preparation.
Embodiment
Below with embodiment technical scheme of the present invention is further described; to help the advantage to technical scheme of the present invention; effect has further to be understood, and embodiment does not limit protection scope of the present invention, and protection scope of the present invention is decided by claim.
Embodiment 1
Ginsenoside Rg1's preparation method:
Ginsenoside Rg1's crude product 30g is dissolved in 50 ℃ the acetone/methanol mixing solutions of 1000ml, the volume ratio of acetone and methyl alcohol is 1: 3, regulates pH to 7 with triethylamine, adds gac again, the constant temperature whip attachment, filter the decarburization degerming, also slowly stir simultaneously lower adding ether 4000ml with the speed cooling of 0.7 ℃/min, the adularescent precipitation produces, be cooled to 0 ℃, filter, drying under reduced pressure 3h obtains the white micro-crystals powder.The particle diameter of described white micro-crystals powder is that particle diameter is 75～180 μ m, yield 85.2%, HPLC content 99.75%.mp：203～205℃。
The X-ray powder diffraction collection of illustrative plates of the ginsenoside Rg1's white micro-crystals powder that obtains locates to demonstrate characteristic diffraction peak at 9.91 °, 12.37 °, 13.60 °, 15.02 °, 16.65 °, 20.20 °, 22.21 °, 22.70 °, 23.35 °, 24.15 °, 25.67 °.
Embodiment 2
Ginsenoside Rg1's preparation method:
Ginsenoside Rg1's crude product 25g is dissolved in 50 ℃ the acetone/methanol mixing solutions of 1000ml, the volume ratio of acetone and methyl alcohol is 1: 3, regulates pH to 7 with triethylamine, adds gac again, the constant temperature whip attachment, filter the decarburization degerming, also slowly stir simultaneously lower adding ether 4000ml with the speed cooling of 0.5 ℃/min, the adularescent precipitation produces, be cooled to 0 ℃, filter, drying under reduced pressure 3h obtains the white micro-crystals powder.The particle diameter of described white micro-crystals powder is that particle diameter is 75～180 μ m, yield 84.6%, HPLC content 99.68%.mp：203～205℃
The X-ray powder diffraction collection of illustrative plates of the ginsenoside Rg1's white micro-crystals powder that obtains and embodiment 1 product has identical parameters.
Embodiment 3
Ginsenoside Rg1's preparation method:
Ginsenoside Rg1's crude product 35g is dissolved in 50 ℃ the acetone/methanol mixing solutions of 1000ml, the volume ratio of acetone and methyl alcohol is 1: 4, regulates pH to 8 with triethylamine, adds gac again, the constant temperature whip attachment, filter the decarburization degerming, also slowly stir simultaneously lower adding ether 3000ml with the speed cooling of 1.0 ℃/min, the adularescent precipitation produces, be cooled to 5 ℃, filter, drying under reduced pressure 3h obtains the white micro-crystals powder.The particle diameter of described white micro-crystals powder is that particle diameter is 75～180 μ m, yield 84.8%, HPLC content 99.71%.mp：203～205℃
The X-ray powder diffraction collection of illustrative plates of the ginsenoside Rg1's white micro-crystals powder that obtains and embodiment 1 product has identical parameters.
Embodiment 4
The preparation method of Radix Notoginseng total arasaponins:
Get Radix Notoginseng total arasaponins bulk drug 10g, sodium-chlor 15mg, be dissolved in the 500ml methyl alcohol, be stirred to abundant dissolving, 0.2 μ m filtering with microporous membrane, upper D101 macroporous adsorbent resin, with 70% ethanolic soln gradient elution, elution flow rate is preferably 0.6ml/min, analyzes the ginsenoside Rg1 with the TLC trace detection, the component that will contain the ginsenoside Rg1 is collected separately and drying under reduced pressure, other component is merged collect.
Dried ginsenoside Rg1's crude product is dissolved in 50 ℃ the acetone/methanol mixing solutions of 140ml, the volume ratio of acetone and methyl alcohol is 1: 3, regulates pH to 7 with triethylamine, adds gac again, the constant temperature whip attachment, filter the decarburization degerming, also slowly stir simultaneously lower adding ether 560ml with the speed cooling of 0.7 ℃/min, the adularescent precipitation produces, be cooled to 0 ℃, filter, drying under reduced pressure 3h obtains the white micro-crystals powder.HPLC content 99.74%.
The X-ray powder diffraction collection of illustrative plates of the ginsenoside Rg1's white micro-crystals powder that obtains and embodiment 1 product has identical parameters, and fusing point is identical.
Add gac to merging in other component of collecting, whip attachment is filtered the decarburization degerming, and drying under reduced pressure 3h obtains white powder.
White micro-crystals powder obtained above and white powder are mixed, namely get Radix Notoginseng total arasaponins provided by the invention, yield 76.2%.This Radix Notoginseng total arasaponins contains ginsenoside Rg1 35.4%, ginsenoside Rb1 31.8%, arasaponin R1 7.2%.
Embodiment 5
The preparation method of Radix Notoginseng total arasaponins:
Get Radix Notoginseng total arasaponins bulk drug 10g, sodium-chlor 25mg, be dissolved in the 333ml methyl alcohol, be stirred to abundant dissolving, 0.2 μ m filtering with microporous membrane, upper D101 macroporous adsorbent resin, with 60% ethanolic soln gradient elution, elution flow rate is preferably 0.5ml/min, analyzes the ginsenoside Rg1 with the TLC trace detection, the component that will contain the ginsenoside Rg1 is collected separately and drying under reduced pressure, other component is merged collect.
Dried ginsenoside Rg1's crude product is dissolved in 50 ℃ the acetone/methanol mixing solutions of 117ml, the volume ratio of acetone and methyl alcohol is 1: 3, regulates pH to 7 with triethylamine, adds gac again, the constant temperature whip attachment, filter the decarburization degerming, also slowly stir simultaneously lower adding ether 468ml with the speed cooling of 0.5 ℃/min, the adularescent precipitation produces, be cooled to 0 ℃, filter, drying under reduced pressure 3h obtains the white micro-crystals powder.
The X-ray powder diffraction collection of illustrative plates of the ginsenoside Rg1's white micro-crystals powder that obtains and embodiment 1 product has identical parameters, and fusing point is identical.
Add gac to merging in other component of collecting, whip attachment is filtered the decarburization degerming, and drying under reduced pressure 3h obtains white powder.HPLC content 99.69%.
White micro-crystals powder obtained above and white powder are mixed, namely get Radix Notoginseng total arasaponins provided by the invention, yield 75.4%.This Radix Notoginseng total arasaponins contains ginsenoside Rg1 36.1%, ginsenoside Rb1 33.1%, arasaponin R1 7.5%.
Embodiment 6
The preparation method of Radix Notoginseng total arasaponins:
Get Radix Notoginseng total arasaponins bulk drug 10g, be dissolved in the 400ml methyl alcohol, be stirred to abundant dissolving, 0.2 μ m filtering with microporous membrane, upper D101 macroporous adsorbent resin, the ethanolic soln gradient elution with 80%, elution flow rate is preferably 1ml/min, analyze the ginsenoside Rg1 with the TLC trace detection, the component that will contain the ginsenoside Rg1 is collected separately and drying under reduced pressure, other component is merged collect.
Dried ginsenoside Rg1's crude product is dissolved in 50 ℃ the acetone/methanol mixing solutions of 100ml, the volume ratio of acetone and methyl alcohol is 1: 4, regulates pH to 8 with triethylamine, adds gac again, the constant temperature whip attachment, filter the decarburization degerming, also slowly stir simultaneously lower adding ether 300ml with the speed cooling of 1.0 ℃/min, the adularescent precipitation produces, be cooled to 5 ℃, filter, drying under reduced pressure 3h obtains the white micro-crystals powder.
The X-ray powder diffraction collection of illustrative plates of the ginsenoside Rg1's white micro-crystals powder that obtains and embodiment 1 product has identical parameters, and fusing point is identical.
Add gac to merging in other component of collecting, whip attachment is filtered the decarburization degerming, and drying under reduced pressure 3h obtains white powder.HPLC content 99.67%.
White micro-crystals powder obtained above and white powder are mixed, namely get Radix Notoginseng total arasaponins provided by the invention, yield 74.1%.This Radix Notoginseng total arasaponins contains ginsenoside Rg1 35.2%, ginsenoside Rb1 31.9%, arasaponin R1 7.2%.
Embodiment 7
The preparation of Effervesce tablet for dredging thrombosis:
Get Radix Notoginseng total arasaponins 50g, tartrate 80g, sodium bicarbonate 120g, sodium starch glycolate 30g, lactose 80g and polyvinylpyrrolidone 20g by the method preparation of embodiment 4, mixing with 95% ethanolic soln softwood processed, is crossed 20 orders and is granulated.Behind particle drying, add again Steviosin 6g, sodium starch glycolate 10g and polyethylene glycol 6000 4g, mixing is pressed into 1000.
Embodiment 8
The preparation of Effervesce tablet for dredging thrombosis:
Get Radix Notoginseng total arasaponins 45g, tartrate 70g, sodium bicarbonate 110g, sodium starch glycolate 27g, lactose 75g and polyvinylpyrrolidone 15g by the method preparation of embodiment 5, mixing with 98% ethanolic soln softwood processed, is crossed 20 orders and is granulated.Behind particle drying, add again Steviosin 5g, sodium starch glycolate 8g and polyethylene glycol 6000 3g, mixing is pressed into 1000.
Embodiment 9
The preparation of Effervesce tablet for dredging thrombosis:
Get Radix Notoginseng total arasaponins 55g, tartrate 85g, sodium bicarbonate 135g, sodium starch glycolate 34g, lactose 85g and polyvinylpyrrolidone 25g by the method preparation of embodiment 6, mixing with 97% ethanolic soln softwood processed, is crossed 20 orders and is granulated.Behind particle drying, add again Steviosin 6g, sodium starch glycolate 11g and polyethylene glycol 6000 4g, mixing is pressed into 1000.
The preparation of Xuesaitong dispersible tablet
Get Radix Notoginseng total arasaponins 50g, cross-linked polyvinylpyrrolidone 30g, low-substituted hydroxypropyl cellulose 15g, Microcrystalline Cellulose 180g by the method preparation of embodiment 4, mixing is that wetting agent is granulated with 95% ethanol, 60 ℃ of dryings, whole grain; Add again sodium starch glycolate 10g, Magnesium Stearate 1g, always mixed 30 minutes; After the passed examination, be pressed into 1000, packing.
Embodiment 11
The preparation of Xuesaitong dispersible tablet
Get Radix Notoginseng total arasaponins 45g, cross-linked polyvinylpyrrolidone 25g, low-substituted hydroxypropyl cellulose 12g, Microcrystalline Cellulose 170g by the method preparation of embodiment 4, mixing is that wetting agent is granulated with 95% ethanol, 60 ℃ of dryings, whole grain; Add again sodium starch glycolate 10g, Magnesium Stearate 1g, always mixed 28 minutes; After the passed examination, be pressed into 1000, packing.
Embodiment 12
The preparation of Xuesaitong dispersible tablet
Get Radix Notoginseng total arasaponins 55g, cross-linked polyvinylpyrrolidone 35g, low-substituted hydroxypropyl cellulose 18g, Microcrystalline Cellulose 190g by the method preparation of embodiment 4, mixing is that wetting agent is granulated with 95% ethanol, 65 ℃ of dryings, whole grain; Add again sodium starch glycolate 10g, Magnesium Stearate 3g, always mixed 35 minutes; After the passed examination, be pressed into 1000, packing.
Experimental example 1
This test example detects residual solvent among the prepared ginsenoside Rg1 of embodiment 1-6, and this test is according to 2010 editions second appendix VIII P of Chinese Pharmacopoeia residual solvent assay method, and it the results are shown in Table 1:
Table 1
| Group | Acetone | Methyl alcohol | Ether | Triethylamine | Ethanol |
| Embodiment 1 | Up to specification | Up to specification | Up to specification | Up to specification | / |
| Embodiment 2 | Up to specification | Up to specification | Up to specification | Up to specification | / |
| Embodiment 3 | Up to specification | Up to specification | Up to specification | Up to specification | / |
| Embodiment 4 | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification |
| Embodiment 5 | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification |
| Embodiment 6 | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification |
Experimental example 2
This experimental example has been investigated the stability of ginsenoside Rg1's crystal provided by the invention
This test is carried out according to 2005 editions second appendix XIX C of Chinese Pharmacopoeia medicine stability test governing principle, and the result is as follows:
Table 2, accelerated test result
| 0 month | 1 month | 3 months | 6 months | 9 months | |
| 1 | 99.94％ | 99.94％ | 99.93％ | 99.92％ | 99.76％ |
| 2 | 100.15％ | 100.15％ | 100.14％ | 100.13％ | 99.83％ |
| 3 | 100.23％ | 100.23％ | 100.23％ | 100.23％ | 99.96％ |
| 4 | 99.97％ | 99.96％ | 99.89％ | 99.73％ | 98.68％ |
| 5 | 100.20％ | 100.20％ | 100.14％ | 99.80％ | 98.83％ |
Table 3, long-term test results
| 0 month | 3 months | 6 months | 9 months | 15 months | 24 months |
| 1 | 99.94％ | 99.93％ | 99.93％ | 99.91％ | 99.87％ | 99.74％ |
| 2 | 100.15％ | 100.14％ | 100.14％ | 100.12％ | 99.99％ | 99.82％ |
| 3 | 100.23％ | 100.23％ | 100.22％ | 100.22％ | 100.09％ | 99.93％ |
| 4 | 99.97％ | 99.97％ | 99.97％ | 99.69％ | 99.31％ | 98.60％ |
| 5 | 100.20％ | 100.20％ | 100.19％ | 99.82％ | 99.45％ | 98.79％ |
Sample 1 is the product of embodiment 1, and sample 2 is the product of embodiment 2, and sample 3 is the product of embodiment 3, and sample 4 is commercially available ginsenoside Rg1's bulk drug, originates from Changning moral health bio tech ltd; Sample 5 is the ginsenoside Rg1 according to the method preparation of embodiment 12 among the patent CN102086223A.
Accelerated test by this experimental example and test of long duration as can be known, compared with prior art, ginsenoside Rg1's provided by the invention stability is better.
Experimental example 3
This test example has been investigated the stability of Effervesce tablet for dredging thrombosis provided by the invention and Xuesaitong dispersible tablet, carries out according to 2005 editions second appendix XIX C of Chinese Pharmacopoeia medicine stability test governing principle.
Sample 6 is Effervesce tablet for dredging thrombosis of embodiment 7 preparations, and sample 7 is Effervesce tablet for dredging thrombosis of embodiment 8 preparations, the Effervesce tablet for dredging thrombosis of sample 8 embodiment 9 preparations, and sample 9 is the Xuesaitong dispersible tablet of embodiment 10 preparations, all simulates commercially available back; Sample 10 is commercially available Effervesce tablet for dredging thrombosis, Fushoutang Pharmaceutical Co., Ltd., and every contains Radix Notoginseng total arasaponins 50mg; Sample 11 is commercially available Effervesce tablet for dredging thrombosis, Yunnan Gulin Natural pharmaceutical Co., Ltd., and every contains Radix Notoginseng total arasaponins 50mg; Accelerated test was placed 6 months under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%, and long-term experiment was placed 12 months under the condition of 25 ℃ ± 2 ℃ of temperature, humidity 60% ± 10%, detected by stable high spot reviews project.
Clarity is with reference to the appendix IX B of 2005 editions II sections of Chinese Pharmacopoeia clarity test procedure in the investigation project.Use the SC series clarity detector of Shanghai Huanghai Sea medicine inspection Instr Ltd..
Illumination range: 1000-4000LX; Time limit scope: 1-99S Set arbitrarily; Power: 30W (single face); Fluorescent tube: 20W (Special fluorescent lamp).
Get test sample 1g, room temperature is dissolved in the 100ml water for injection, uses KJ-202 type vibrator with 1000 beats/mins of vibrations 1 minute, leaves standstill quantitative check clarity.
Table 4 accelerated test result
Table 5 long-term test results
This description of test, Effervesce tablet for dredging thrombosis provided by the invention and Xuesaitong dispersible tablet good stability accelerate, test of long duration purity content is little, and foreign matter content is few, the liquid clarification after the standing storage dissolving.And the Effervesce tablet for dredging thrombosis poor stability of prior art, 24 months impurity content exceeding indexs of accelerated test 9 months and test of long duration, active component content are defective.
The other embodiments of the invention product has also carried out identical experiment, and obtains the experimental result of same trend, but length limits, and the present invention enumerates no longer one by one.
Claims (10)
1. the ginsenoside Rg1 of a formula I, it is characterized in that, described ginsenoside Rg1 is crystal, and the X-ray powder diffraction that described ginsenoside Rg1 uses the Cu-K alpha-ray to measure is 9.91 °, 12.37 °, 13.60 °, 15.02 °, 16.65 °, 20.20 °, 22.21 °, 22.70 °, 23.35 °, 24.15 °, 25.67 ° at 2 θ and locates to show characteristic peak;
2. a ginsenoside Rg1 claimed in claim 1 preparation method, it is characterized in that, described ginsenoside Rg1's preparation method comprises: ginsenoside Rg1's crude product is dissolved in 45～55 ℃ of acetone/methanol mixing solutionss, wherein acetone and methyl alcohol are made into mixing solutions with 1: 3～4 volume ratio, regulate pH to 7～8 with triethylamine, add again gac, the constant temperature whip attachment, filter the decarburization degerming, with the speed cooling of 0.5～1.0 ℃/min and slowly add simultaneously ether, the consumption of described ether is 3～4 times of the volumes of acetone/methanol mixing solutions, be cooled to 0～5 ℃, filter, drying under reduced pressure obtains the white micro-crystals powder.
3. preparation method according to claim 2 is characterized in that, per 25～35mg ginsenoside Rg1 dissolving crude product is in 1ml acetone/methanol mixing solutions.
4. a medicinal compositions is characterized in that, described medicinal compositions comprises a kind of Radix Notoginseng total arasaponins that contains ginsenoside Rg1 claimed in claim 1.
5. medicinal compositions according to claim 4, it is characterized in that, described medicinal compositions is Effervesce tablet for dredging thrombosis, in weight part, described Effervesce tablet for dredging thrombosis comprises 45～55 parts of Radix Notoginseng total arasaponinss, 70～85 parts in tartrate, 110～135 parts of sodium bicarbonates, 35～45 parts of sodium starch glycolatees, 75～85 parts of lactose, 15～25 parts of polyvinylpyrrolidones, 5～6 parts of Steviosins, 3～4 parts of polyethylene glycol 6000s.
6. medicinal compositions according to claim 4, it is characterized in that, described medicinal compositions is Xuesaitong dispersible tablet, in weight part, described Xuesaitong dispersible tablet comprises 45～55 parts of Radix Notoginseng total arasaponinss, 25～35 parts of cross-linked polyvinylpyrrolidones, 12～18 parts of low-substituted hydroxypropyl celluloses, 170～190 parts of Microcrystalline Celluloses, 1～3 part of Magnesium Stearate, 10 parts of sodium starch glycolatees.
7. each described medicinal compositions is characterized in that according to claim 4-6, and the preparation method of described Radix Notoginseng total arasaponins may further comprise the steps:
(1) gets the Radix Notoginseng total arasaponins bulk drug of recipe quantity, be dissolved in the methyl alcohol filtering with microporous membrane fully, upper macroporous adsorbent resin, ethanolic soln gradient elution with 60～80%, the component that will contain the ginsenoside Rg1 is collected separately and drying under reduced pressure, other component is merged collect;
(2) dried ginsenoside Rg1's crude product is dissolved in 45～55 ℃ of acetone/methanol mixing solutionss, wherein acetone and methyl alcohol are made into mixing solutions with 1: 3～4 volume ratio, regulate pH to 7～8 with triethylamine, add again gac, the constant temperature whip attachment, filter the decarburization degerming, speed cooling and while with 0.5～1.0 ℃/min slowly add ether, the consumption of described ether is 3～4 times of the volumes of acetone/methanol mixing solutions, be cooled to 0～5 ℃, filter, drying under reduced pressure obtains the white micro-crystals powder;
(3) add gac to merging in other component of collecting, whip attachment is filtered the decarburization degerming, and drying under reduced pressure obtains white powder;
(4) white powder that the white micro-crystals powder that step (2) is obtained and step (3) obtain mixes, and namely gets Radix Notoginseng total arasaponins.
8. pharmaceutical composition according to claim 7 is characterized in that, in the described step (1), the consumption of Radix Notoginseng total arasaponins bulk drug and methyl alcohol is dissolved in 1ml methyl alcohol by per 20～30mg Radix Notoginseng total arasaponins bulk drug.
9. described pharmaceutical composition according to claim 7 is characterized in that, in the described step (1), also adds the sodium-chlor of 3～5%mg/ml in the methyl alcohol.
10. described pharmaceutical composition according to claim 7 is characterized in that, in the described step (1), the model of macroporous adsorbent resin is D101, and elution flow rate is 0.5～1ml/min.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1723971A (en) * | 2005-07-22 | 2006-01-25 | 福寿堂制药有限公司 | Effervescent tables for treating thrombus, and its prepn. method |
| CN101463061A (en) * | 2007-12-21 | 2009-06-24 | 中国医学科学院药物研究所 | Ginseng saponin Rg1 and Rb1 in pseudo-ginseng and preparation of total saponin thereof |
| CN101537026A (en) * | 2009-04-24 | 2009-09-23 | 河北兆康制药有限公司 | Xuesaitong dispersible tablet and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1723971A (en) * | 2005-07-22 | 2006-01-25 | 福寿堂制药有限公司 | Effervescent tables for treating thrombus, and its prepn. method |
| CN101463061A (en) * | 2007-12-21 | 2009-06-24 | 中国医学科学院药物研究所 | Ginseng saponin Rg1 and Rb1 in pseudo-ginseng and preparation of total saponin thereof |
| CN101537026A (en) * | 2009-04-24 | 2009-09-23 | 河北兆康制药有限公司 | Xuesaitong dispersible tablet and preparation method thereof |
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