CN104119416B - A kind of ginsenoside Rb 3compound and containing the Qiyeshen an dispersible tablet of this compound and Qiyeshen' and tablet - Google Patents
A kind of ginsenoside Rb 3compound and containing the Qiyeshen an dispersible tablet of this compound and Qiyeshen' and tablet Download PDFInfo
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Abstract
The present invention relates to a kind of ginsenoside Rb
3compound, described ginsenoside Rb
3as shown in Figure 1, its structural formula is such as formula shown in I for the X-ray powder diffraction pattern that compound uses the measurement of Cu-K alpha-ray to obtain.The invention still further relates to a kind of containing ginsenoside Rb
3the Qiyeshen an dispersible tablet of compound and Qiyeshen' and tablet.The Qiyeshen an dispersible tablet that the present invention prepares and Qiyeshen' and tablet, its analgesia, calmness and syngignoscism are better than ordinary preparation.
Description
Technical field
The present invention relates to pharmacy field, specifically, relate to a kind of containing ginsenoside Rb
3compound and containing the Qiyeshen an dispersible tablet of this compound and Qiyeshen' and tablet.
Background technology
Qiyeshen' and tablet is the new drug developed with the Folium Notoginseng total arasaponins Modern preparations technology of Sanchi Leaf Hydrolysis kinetics, prove there is benefiting vital QI for tranquillizing through pharmacology, toxicity and clinical trial etc., promoting blood circulation and stopping pain, the effects such as hemostasis, and toxicity is less, without the tolerance of medicine and additive, for the palpitaition caused by deficiency of heart-QI, insomnia.
At present, a lot of several formulations about Qiyeshen' and tablet is disclosed, such as:
ZL02134076.5 discloses a kind of Qiyeshen an dripping pill curing mainly the diseases such as insomnia, its preparation method is: in Folium Notoginseng glycoside: water-soluble base=1: the ratio of 1 ~ 1: 5 carries out material combination, and in water-bath, dissolving, instillation condensing agent, the technique such as shaping is prepared from.
ZL200610010680.0 discloses a kind of Qiyeshen an orally disintegrating tablet, with Qiyeshen an (Sanchi Leaf Total saponin) for raw material, weighting agent, disintegrating agent, correctives, glidant, lubricant etc. are auxiliary material, tackiness agent, capsule material or coating material can be used according to different situations, also can take the circumstances into consideration to add appropriate effervescent, then obtain through specific preparation method's preparation.
And in order to the uptake rate that improves Qiyeshen an preparation further and clinical effectiveness, special the present invention is proposed.
Summary of the invention
Primary goal of the invention of the present invention is to provide a kind of ginsenoside Rb
3compound.
Second goal of the invention of the present invention is to provide a kind of containing ginsenoside Rb
3the Qiyeshen an dispersible tablet of compound and Qiyeshen' and tablet.
In order to complete object of the present invention, the technical scheme of employing is:
A kind of ginsenoside Rb
3compound, described ginsenoside Rb
3as shown in Figure 1, its structural formula is such as formula shown in I for the X-ray powder diffraction pattern that compound uses the measurement of Cu-K alpha-ray to obtain:
Wherein, the preparation method of this compound is:
(1) compare Folium Notoginseng total arasaponins raw material and column chromatography silica gel weight for 1:40 application of sample, through silica gel column chromatography, volume ratio is the elution of the chloroform-methanol-water of 6:4:1; Every flow point 500mL, gained flow point carries out merging 151 ~ 173 flow points after TLC checks;
(2) described flow point is again through silica gel column chromatography, and employing volume ratio is the elution of 4:l:2 propyl carbinol-ethyl acetate-water, every flow point 500mL, and gained flow point carries out merging 8 ~ 18 flow points after TLC checks, prepares ginsenoside Rb through preparative chromatography
3crude product;
(3) ginsenoside Rb is got
3crude product adds stirring and dissolving in the ethanolic soln of 90 ~ 100%, and stirring velocity is 120 ~ 180 revs/min; Treat ginsenoside Rb
3after crude product dissolves completely, to ginsenoside Rb
3add the mixing solutions of 0 ~ 5 DEG C of hexanaphthene and ether in ethanolic soln, limit edged stirs, and stirring velocity is 60 ~ 120 revs/min; After mixing solutions adds, leave standstill growing the grain 1 ~ 4 hour; Filter after obtaining crystal, distilled water wash, vacuum-drying 1 ~ 4 hour, obtains ginsenoside Rb
3crystal.
Wherein, in step (3), the volume ratio of described hexanaphthene and the mixing solutions of ether is 1:1 ~ 5; Preferred 1:2 ~ 5; The volume of described hexanaphthene and the mixing solutions of ether and ginsenoside Rb
3the volume ratio of ethanolic soln is 1 ~ 5:1; Preferably 2 ~ 4:1.
The invention still further relates to containing ginsenoside Rb
3the pharmaceutical composition of compound, described pharmaceutical composition is by containing ginsenoside Rb
3the Folium Notoginseng total arasaponins of compound and excipient substance composition; The process for purification of described Folium Notoginseng total arasaponins comprises the following steps:
(1) compare Folium Notoginseng total arasaponins raw material and column chromatography silica gel weight for 1:40 application of sample, through silica gel column chromatography, volume ratio is the elution of the chloroform-methanol-water of 6:4:1; Every flow point 500mL, gained flow point carries out merging 151 ~ 173 flow points after TLC checks;
(2) described flow point is again through silica gel column chromatography, and employing volume ratio is the elution of 4:l:2 propyl carbinol-ethyl acetate-water, every flow point 500mL, and gained flow point carries out merging 8 ~ 18 flow points after TLC checks, prepares ginsenoside Rb through preparative chromatography
3crude product; Get ginsenoside Rb
3crude product adds stirring and dissolving in the ethanolic soln of 90 ~ 100%, and stirring velocity is 120 ~ 180 revs/min; Treat ginsenoside Rb
3after crude product dissolves completely, to ginsenoside Rb
3add the mixing solutions of 0 ~ 5 DEG C of hexanaphthene and ether in ethanolic soln, limit edged stirs, and stirring velocity is 60 ~ 120 revs/min; After mixing solutions adds, leave standstill growing the grain 1 ~ 4 hour; Filter after obtaining crystal, distilled water wash, vacuum-drying 1 ~ 4 hour, obtains ginsenoside Rb
3crystal;
(3) ginsenoside Rb is separated
3after cut concentrating under reduced pressure, vacuum-drying, pulverize obtain fine powder;
(4) the ginsenoside Rb will prepared in step (2)
3crystal mixes with the fine powder in step (3), obtains containing ginsenoside Rb
3compound Folium Notoginseng total arasaponins.
The preparation of pharmaceutical composition of the present invention comprises Qiyeshen an dispersible tablet or Qiyeshen' and tablet.Wherein, containing Folium Notoginseng total arasaponins 30 ~ 50 weight part, pregelatinized Starch 20 ~ 40 weight part, sodium starch glycolate 30 ~ 60 weight part in Qiyeshen an dispersible tablet, silicon-dioxide 35 ~ 70 weight part, croscarmellose sodium 7 ~ 14 weight part, Microcrystalline Cellulose 20 ~ 38 weight part, Magnesium Stearate 1 ~ 2 weight part; Preferably, containing Folium Notoginseng total arasaponins 40 ~ 50 weight part, pregelatinized Starch 30 ~ 40 weight part, sodium starch glycolate 50 ~ 60 weight part in Qiyeshen an dispersible tablet, silicon-dioxide 60 ~ 70 weight part, croscarmellose sodium 10 ~ 14 weight part, Microcrystalline Cellulose 32 ~ 38 weight part, Magnesium Stearate 1 ~ 2 weight part.Containing Folium Notoginseng total arasaponins 30 ~ 50 weight part, pregelatinized Starch 30 ~ 50 weight part, Microcrystalline Cellulose 60 ~ 100 weight part, carboxymethylstach sodium 10 ~ 20 weight part, magnesium stearate 1 ~ 2 weight part in Qiyeshen' and tablet.Preferably, containing Folium Notoginseng total arasaponins 40 ~ 50 weight part, pregelatinized Starch 40 ~ 50 weight part, Microcrystalline Cellulose 80 ~ 100 weight part, carboxymethylstach sodium 15 ~ 20 weight part, magnesium stearate 1.5 ~ 2 weight part.
The present invention will be further explained below.
On the basis that the present invention studies for many years, carried out further purifying and crystallization to Folium Notoginseng total arasaponins, pleasantly surprised obtains a kind of ginsenoside Rb
3new crystal, the X-ray powder diffraction pattern that this crystalline compounds uses the measurement of Cu-K alpha-ray to obtain is as shown in Figure 1.Its structure is through proton nmr spectra and carbon spectrum confirmation.Its proterties is white crystalline powder.Its crystalline structure and the ginsenoside Rb after directly purifying
3crystalline structure there occurs change, and after water or organic solvent dissolution, crystal formation does not change.
The present invention is carrying out finding in pharmacodynamics test, adopts ginsenoside Rb
3the pharmaceutical composition that in crystal and Folium Notoginseng total arasaponins, other effective constituents form, its drug effect is better than the preparation adopting Folium Notoginseng total arasaponins directly to prepare.This may be due to, preparing ginsenoside Rb
3eliminate impurity in the process of crystal, or eliminate and to have nothing to do with the property of medicine or the material of antagonism, and improve purity; Or by crystallization, change ginsenoside Rb
3solvability or liberation degree, thus make it more easily be absorbed in vivo, thus drug effect improved.
The invention still further relates to a kind of containing ginsenoside Rb
3the Qiyeshen an dispersible tablet of compound and Qiyeshen' and tablet.The present invention, by further research to Folium Notoginseng total arasaponins effective constituent, has prepared the preparation containing Folium Notoginseng total arasaponins that a kind of stability and drug effect are all improved.The Qiyeshen an dispersible tablet that the present invention prepares and Qiyeshen' and tablet, its analgesia, calmness and syngignoscism are better than ordinary preparation.Meanwhile, the present invention, by further screening auxiliary material, has prepared the better preparation of the effect such as stability, dissolution rate.
Accompanying drawing illustrates:
Fig. 1 is the ginsenoside Rb that embodiment 1 prepares
3the X-ray powder diffraction pattern that crystal uses the measurement of Cu-K alpha-ray to obtain.
Embodiments of the invention are only limitted to make further explanation content of the present invention, do not limit Composition of contents of the present invention.
Embodiment
Embodiment 1
1. by Folium Notoginseng total arasaponins raw material 30g and column chromatography silica gel (200 ~ 300 order) by weight being 1:40 application of sample, through silica gel column chromatography, volume ratio is the elution of the chloroform-methanol-water of 6:4:1; Every flow point 500mL, collects 198 flow points altogether, and gained flow point merges 151 ~ 173 flow points after being checked by TLC;
2. flow point described in is again through silicagel column (200 ~ 300 order) chromatography, and employing volume ratio is the elution of the propyl carbinol-ethyl acetate-water of 4:l:2, and every flow point 500mL, collects 32 flow points altogether; Gained flow point merges 8 ~ 18 flow points after being checked by TLC, is separated prepares ginsenoside Rb through preparative chromatography
3crude product; Ginsenoside Rb is accredited as through thin-layer chromatography and proton nmr spectra, carbon spectrum after chromatographic separation
3compound; Wherein, the condition of preparative chromatography is:
Chromatographic column: SinoChromODS-BP5 μm, diameter 10mm × 250mm;
Moving phase: acetonitrile (A)-water (B): the degree such as 0 ~ 180min, 31%A, the degree such as 180 ~ 300min, 45%A; Volumetric flow rate: 0.8ml/min;
Sample quality concentration: 100mg/ml, sample size: 500 μ l, column temperature: room temperature, determined wavelength: 203nm;
3. recrystallization: get ginsenoside Rb
3crude product adds stirring and dissolving in the ethanolic soln of 90%, and stirring velocity is 120 revs/min; Treat ginsenoside Rb
3after crude product dissolves completely, to ginsenoside Rb
3add the mixing solutions of 0 DEG C of hexanaphthene and ether in ethanolic soln, limit edged stirs, and stirring velocity is 60 revs/min; The volume ratio of the mixing solutions of hexanaphthene and ether is 1:2, the volume of the mixing solutions of hexanaphthene and ether and ginsenoside Rb
3the volume ratio of ethanolic soln is 4:1; After mixing solutions adds, leave standstill growing the grain 3 hours; Filter after obtaining crystal, distilled water wash, vacuum-drying 4 hours, obtains ginsenoside Rb
3crystal.The ginsenoside Rb prepared
3as shown in Figure 1, its purity is 99.93% to the X-ray powder diffraction that crystal uses the measurement of Cu-K alpha-ray to obtain, and solvent trace (<0.001%), its structure is confirmed through proton nmr spectra.
4. be separated ginsenoside Rb
3after cut concentrating under reduced pressure, vacuum-drying, pulverize obtain fine powder;
5. the ginsenoside Rb will prepared in step 3
3crystal mixes with the fine powder in step 4, obtains Folium Notoginseng total arasaponins effective constituent mixture, prepares Qiyeshen an dispersible tablet or Qiyeshen' and tablet.
Embodiment 2
1. by Folium Notoginseng total arasaponins raw material 30g and column chromatography silica gel (200 ~ 300 order) by weight being 1:40 application of sample, through silica gel column chromatography, volume ratio is the elution of the chloroform-methanol-water of 6:4:1; Every flow point 500mL, collects 198 flow points altogether, and gained flow point merges 151 ~ 173 flow points after being checked by TLC;
2. flow point described in is again through silicagel column (200 ~ 300 order) chromatography, and by weight being 1:40 application of sample, employing volume ratio is the elution of the propyl carbinol-ethyl acetate-water of 4:l:2, and every flow point 500mL, collects 32 flow points altogether; Gained flow point merges 8 ~ 18 flow points after being checked by TLC, is separated prepares ginsenoside Rb through preparative chromatography
3crystal; Ginsenoside Rb is accredited as through thin-layer chromatography and proton nmr spectra, carbon spectrum after chromatographic separation
3; Wherein, the condition of preparative chromatography is:
Chromatographic column: SinoChromODS-BP5 μm, diameter 10mm × 250mm;
Moving phase: acetonitrile (A)-water (B); The degree such as 0 ~ 180min, 31%A, the degree such as 180 ~ 300min, 45%A;
Volumetric flow rate: 0.8ml/min;
Sample quality concentration: 100mg/ml, sample size: 500 μ l, column temperature: room temperature, determined wavelength: 203nm;
3. recrystallization: get ginsenoside Rb
3crude product adds stirring and dissolving in the ethanolic soln of 100%, and stirring velocity is 180 revs/min; Treat ginsenoside crude product Rb
3after dissolving completely, to ginsenoside Rb
3add the mixing solutions of 5 DEG C of hexanaphthenes and ether in ethanolic soln, limit edged stirs, and stirring velocity is 120 revs/min; The volume ratio of the mixing solutions of hexanaphthene and ether is 1:5; The volume of the mixing solutions of hexanaphthene and ether and ginsenoside Rb
3the volume ratio of ethanolic soln is 5:1; After mixing solutions adds, leave standstill growing the grain 4 hours; Filter after obtaining crystal, distilled water wash, vacuum-drying 4 hours, obtains ginsenoside Rb
3crystal.The ginsenoside Rb prepared
3as shown in Figure 1, its purity is 99.92% to the X-ray powder diffraction that crystal uses the measurement of Cu-K alpha-ray to obtain, and solvent trace (<0.001%), its structure is confirmed through proton nmr spectra.
4. be separated ginsenoside Rb
3after filtrate reduced in volume, vacuum-drying, pulverize obtain fine powder;
5. the ginsenoside Rb will prepared in step 3
3crystal mixes with the fine powder in step 4, obtains Folium Notoginseng total arasaponins effective constituent mixture, prepares Qiyeshen an dispersible tablet or Qiyeshen' and tablet.
Embodiment 3 ~ 5: the preparation of Qiyeshen an dispersible tablet
Its formula is as shown in table 1, the Folium Notoginseng total arasaponins effective constituent mixture that Example 1 prepares, add pregelatinized Starch, sodium starch glycolate, silicon-dioxide, croscarmellose sodium, Microcrystalline Cellulose fully mix, granulate with 5% PVP K30 hydrotropic solution, dry at 50 ~ 60 DEG C, whole grain, add magnesium stearate, mixing, is pressed into 1000, and every containing Folium Notoginseng total arasaponins 50mg.
Table 1: unit (g)
Table 2: 3 batches of quality measurements of embodiment 5 are:
Embodiment 6 ~ 8: the preparation of Qiyeshen' and tablet
Its formula is as shown in table 3, the Folium Notoginseng total arasaponins effective constituent mixture that Example 2 prepares, add Microcrystalline Cellulose, pregelatinized Starch, carboxymethylstach sodium fully mix, granulate with 80% ethanolic soln, dry at 70 ~ 80 DEG C, whole grain, add Magnesium Stearate, mixing, is pressed into 1000, adopt the molten damp-proof coating powder of Opadry series stomach of the happy Kanggong department of card to carry out dressing, to obtain final product.
Wherein, art for coating operation steps is: first put in coating pan by the plain sheet suppressed, rotate preheating 5 minutes, the suitable rotating speed of adjustment, carries out spray coating, control flow (0.10 ~ 0.15kg/min), dressing, to label weightening finish about 3%, continues to use warm air drying 10 ~ 15 minutes, obtains product, through packaging, get product after the assay was approved.Coating liquid concentration is 14%, and flow is 0.10 ~ 0.15kg/min, and pellet moisture is 3 ~ 5%, and plain sheet hardness is 3 ~ 4kg/mm
2.
Table 3: unit (g)
| Folium Notoginseng total arasaponins effective constituent mixture | Pregelatinized Starch | Microcrystalline Cellulose | Carboxymethylstach sodium | Magnesium stearate | |
| Embodiment 6 | 50 | 50 | 100 | 20 | 2 |
| Embodiment 7 | 50 | 40 | 80 | 15 | 1.5 |
| Embodiment 8 | 50 | 30 | 60 | 10 | 1 |
After testing, the indices of this tablet conforms with the regulations.
Experimental example 1: experimentation on animals
1. instrument and reagent: CJ-I photoelectricity register (Tianjin medicine equipment repair plant), etidocine tablet (pharmaceutical factory of Jintan City of Jiangsu Province), diazepam (5mg/ sheet, Jiangsu Ji Chuan pharmaceutical factory product); Comparative formulation (adopt commercially available Folium Notoginseng total arasaponins raw material, prepare dispersible tablet according to the formula of embodiment 5 and method)
1.2 animals: ICR mouse, body weight 18 ~ 20g;
2 methods and result
2.1 method
2.1.1 writhing test
Get mouse 50, be divided into 5 groups at random, male and female half and half.
Blank group: feedwater;
Experimental group: Qiyeshen an dispersible tablet 50mg effective constituent/kg that embodiment 5 prepares;
Comparative group: Comparative formulation 50mg effective constituent/kg;
Positive controls: etidocine tablet liquid 20mg/kg;
40min after administration, each treated animal equal abdominal injection 0.6% acetic acid 10ml/kg induced pain, every animal writhing number of times in 20min after record injection algogen.
2.1.2 calm test
Get mouse 50, be divided into 5 groups at random, male and female half and half.
Blank group: feedwater;
Experimental group: Qiyeshen an dispersible tablet 50mg effective constituent/kg that embodiment 5 prepares;
Comparative group: Comparative formulation 50mg effective constituent/kg;
Positive controls: diazepam: 4mg/kg.
40min after administration, puts a mouse in people's photoelectric counting box at every turn, first adapts to 5min, then records the movable number of times of mouse in 10min.
2.1.3 hypnosis test
Get male mice 50 and be divided into 5 groups at random;
Blank group: feedwater;
Experimental group: Qiyeshen an dispersible tablet 50mg effective constituent/kg that embodiment 5 prepares;
Comparative group: Comparative formulation 50mg effective constituent/kg;
Positive controls: diazepam 4mg/kg.
40min after administration, abdominal injection threshold dose Nembutal sodium solution 20ml/kg, with righting reflex loss be fall asleep, with righting reflex loss to time of recovery for sleep time.
2.2 experimental result
Table 4: that reacts mouse writhing affects n=10X ± SD
| Group | Dosage (mg/kg) | Writhing number of times (secondary) | Inhibiting rate (%) | P |
| Blank | — | 19.3±4.1 | — | — |
| Experimental group | 50 | 5.9±3.8 | 69.4 | <0.001 |
| Comparative group | 50 | 13.9±3.7 | 28.0 | 0.05 |
| Positive control | 20 | 4.6±2.8 | 76.2 | <0.001 |
Table 5: n=10X ± SD is affected on spontaneous activity in mice
| Group | Dosage (mg/kg) | Movable number of times (secondary) | Inhibiting rate (%) | P |
| Blank | — | 1026±108 | — | — |
| Experimental group | 50 | 425±35 | 58.6 | <0.001 |
| Comparative group | 50 | 819±142 | 20.2 | <0.01 |
| Stable group | 4 | 74±2 | 92.8 | <0.001 |
Table 6: n=10X ± SD is affected on mice sleep
| Group | Dosage (mg/kg) | The length of one's sleep (min) | P |
| Blank | — | 8.6±3.2 | — |
| Experimental group | 50 | 25.5±3.5 | <0.001 |
| Comparative group | 50 | 13.7±4.2 | <0.01 |
| Stable group | 4 | 48.2±12.6 | <0.001 |
Known by this test example, the Qiyeshen an dispersible tablet that the present invention prepares, its analgesia, calmness and syngignoscism are better than common dispersible tablet.
The present invention carries out same experiment to dripping pill, the experimental result obtained and the present invention similar, the drug action that proved invents the Qiyeshen an dripping pill prepared is better than common dripping pill.
Experimental example 4: dissolution determination
1. material
The Comparative formulation for preparing in the Qiyeshen an dispersible tablet that Example 5 prepares and experimental example 3 (adopt commercially available Folium Notoginseng total arasaponins raw material, prepare dispersible tablet according to the formula of embodiment 5 and method) ginsenoside Rb3 reference substance is provided by Nat'l Pharmaceutical & Biological Products Control Institute.Acetonitrile is chromatographically pure; Water is distilled water (self-control), and all the other reagent are analytical pure.
2. method and result
2.1 chromatographic condition: AichromC18 post (250mm × 4.6mm, 5 μm) is chromatographic column; Acetonitrile-water-glacial acetic acid (32:68:0.08) is moving phase; Volumetric flow rate: 1.0mL/min; Column temperature: 30 DEG C; Determined wavelength: 203nm.
The preparation of 2.2 solution
2.2.1 the preparation of reference substance solution: get ginsenoside Rb
3reference substance is appropriate, accurately weighed, adds methyl alcohol and makes 242Lg/mL solution, in contrast product solution.
2.2.2 the preparation of need testing solution:
Get 6, each group of preparation with degassed water 250mL for dissolution medium, temperature controls in (37 ± 0.5) DEG C, rotating speed 100r/min, sample enters release pond to start to clock instantaneously, during to 30min, appropriate in regulation sampling spot draw solution, filter immediately, after subsequent filtrate high speed centrifugation, get supernatant liquor as need testing solution.
2.2.3 the preparation of negative solution:
Take auxiliary material except Radix Notoginseng total arasaponins as micropowder silica gel, pregelatinized Starch etc. in prescription ratio, make negative sample according to preparation process, and prepare negative control solution by the solution manufacturing method of trial-product.
2.3 the mensuration of dissolution rate
2.3.1 the selection of dissolution medium and volume: because in this product, the amount of ginsenoside Rb3 is limited, for ensureing that detected level is in limits, (liquor capacity is 250mL to select China's coastal port two annex XIIIC dissolution rate the 3rd methods and small-radius curve track, paddle board method, rotating speed is 100r/min, and medium is water).
2.3.2 the determination of dissolution determination method: get 6, each group of preparation with degassed water 250mL for dissolution medium, temperature controls in (37 ± 0.5) DEG C, rotating speed 100r/min, sample enters release pond to start to clock instantaneously, respectively 0,3,5,10,15,20,30min time sampling 2mL (supplementing the dissolution medium of equal-volume uniform temp) simultaneously, filter immediately, after subsequent filtrate high speed centrifugation, get supernatant liquor sample introduction.Get 20 μ L ginsenoside Rb3 reference substance solution sample introductions simultaneously, calculate mass concentration and the cumulative leaching rate of ginsenoside Rb3.
2.3.3 dissolution determination: get 2 groups of samples, often organize 6, according to above conditional operation, respectively 0,3,5,10,15,20,30min time sampling 2mL (supplementing the dissolution medium of equal-volume uniform temp) simultaneously, filter immediately, after subsequent filtrate high speed centrifugation, get supernatant liquor sample introduction, record color atlas, calculates ginsenoside Rb3 cumulative leaching rate, as shown in table 7:
Table 7:
| Time (minute) | 3 | 5 | 10 | 15 | 20 | 30 |
| Comparative formulation | 38.25 | 65.13 | 73.13 | 78.58 | 86.67 | 95.15 |
| Embodiment 5 | 48.76 | 80.67 | 88.32 | 92.68 | 97.67 | 100.12 |
Confirm through experiment, the dispersible tablet that the dissolution rate of the dispersible tablet adopting Folium Notoginseng total arasaponins active fraction preparation of the present invention to obtain prepares higher than common Folium Notoginseng total arasaponins raw material, this may be due in the process of process activeconstituents, activeconstituents is carried out to the treatment steps such as concentrating under reduced pressure, drying, purification crystal, thus enhanced the speed of activeconstituents stripping from dispersible tablet.
Claims (12)
1. a ginsenoside Rb
3crystalline compounds, is characterized in that, described ginsenoside Rb
3as shown in Figure 1, its structural formula is such as formula shown in I for the X-ray powder diffraction pattern that compound uses the measurement of Cu-K alpha-ray to obtain:
2. ginsenoside Rb according to claim 1
3crystalline compounds, is characterized in that, the preparation method of described compound is:
(1) compare Folium Notoginseng total arasaponins raw material and column chromatography silica gel weight for 1:40 application of sample, through silica gel column chromatography, volume ratio is the elution of the chloroform-methanol-water of 6:4:1; Every flow point 500mL, gained flow point carries out merging 151 ~ 173 flow points after TLC checks;
(2) described flow point is again through silica gel column chromatography, and employing volume ratio is the elution of 4:l:2 propyl carbinol-ethyl acetate-water, every flow point 500mL, and gained flow point carries out merging 8 ~ 18 flow points after TLC checks, prepares ginsenoside Rb through preparative chromatography
3crude product;
(3) ginsenoside Rb is got
3crude product adds stirring and dissolving in the ethanolic soln of 90 ~ 100%, and stirring velocity is 120 ~ 180 revs/min; Treat ginsenoside Rb
3after crude product dissolves completely, to ginsenoside Rb
3add the mixing solutions of 0 ~ 5 DEG C of hexanaphthene and ether in ethanolic soln, limit edged stirs, and stirring velocity is 60 ~ 120 revs/min; After mixing solutions adds, leave standstill growing the grain 1 ~ 4 hour; Filter after obtaining crystal, distilled water wash, vacuum-drying 1 ~ 4 hour, obtains ginsenoside Rb
3crystal.
3. ginsenoside Rb according to claim 2
3crystalline compounds, is characterized in that, in step (3), the volume ratio of described hexanaphthene and the mixing solutions of ether is 1:1 ~ 5.
4. ginsenoside Rb according to claim 3
3crystalline compounds, is characterized in that, the volume ratio of described hexanaphthene and the mixing solutions of ether is 1:2 ~ 5.
5. ginsenoside Rb according to claim 2
3crystalline compounds, is characterized in that, in step (3), and the volume of described hexanaphthene and the mixing solutions of ether and ginsenoside Rb
3the volume ratio of ethanolic soln is 1 ~ 5:1.
6. ginsenoside Rb according to claim 5
3crystalline compounds, is characterized in that, the volume of described hexanaphthene and the mixing solutions of ether and ginsenoside Rb
3the volume ratio of ethanolic soln is 2 ~ 4:1.
7. one kind contains ginsenoside Rb containing according to claim 1
3the pharmaceutical composition of crystalline compounds, is characterized in that, described pharmaceutical composition is by containing ginsenoside Rb
3the Folium Notoginseng total arasaponins of compound and excipient substance composition; The process for purification of described Folium Notoginseng total arasaponins comprises the following steps:
(1) compare Folium Notoginseng total arasaponins raw material and column chromatography silica gel weight for 1:40 application of sample, through silica gel column chromatography, volume ratio is the elution of the chloroform-methanol-water of 6:4:1; Every flow point 500mL, gained flow point carries out merging 151 ~ 173 flow points after TLC checks;
(2) described flow point is again through silica gel column chromatography, and employing volume ratio is the elution of 4:l:2 propyl carbinol-ethyl acetate-water, every flow point 500mL, and gained flow point carries out merging 8 ~ 18 flow points after TLC checks, prepares ginsenoside Rb through preparative chromatography
3crude product; Get ginsenoside Rb
3crude product adds stirring and dissolving in the ethanolic soln of 90 ~ 100%, and stirring velocity is 120 ~ 180 revs/min; Treat ginsenoside Rb
3after crude product dissolves completely, to ginsenoside Rb
3add the mixing solutions of 0 ~ 5 DEG C of hexanaphthene and ether in ethanolic soln, limit edged stirs, and stirring velocity is 60 ~ 120 revs/min; After mixing solutions adds, leave standstill growing the grain 1 ~ 4 hour; Filter after obtaining crystal, distilled water wash, vacuum-drying 1 ~ 4 hour, obtains ginsenoside Rb
3crystal;
(3) ginsenoside Rb is separated
3after cut concentrating under reduced pressure, vacuum-drying, pulverize obtain fine powder;
(4) the ginsenoside Rb will prepared in step (2)
3crystal mixes with the fine powder in step (3), obtains containing ginsenoside Rb
3compound Folium Notoginseng total arasaponins.
8. according to claim 7 containing ginsenoside Rb
3the pharmaceutical composition of crystalline compounds, is characterized in that, the preparation of described composition comprises Qiyeshen an dispersible tablet or Qiyeshen' and tablet.
9. according to claim 8 containing ginsenoside Rb
3the pharmaceutical composition of crystalline compounds, it is characterized in that, containing Folium Notoginseng total arasaponins 30 ~ 50 weight part, pregelatinized Starch 20 ~ 40 weight part, sodium starch glycolate 30 ~ 60 weight part in described Qiyeshen an dispersible tablet, silicon-dioxide 35 ~ 70 weight part, croscarmellose sodium 7 ~ 14 weight part, Microcrystalline Cellulose 20 ~ 38 weight part, Magnesium Stearate 1 ~ 2 weight part.
10. according to claim 8 containing ginsenoside Rb
3the pharmaceutical composition of crystalline compounds, it is characterized in that, containing Folium Notoginseng total arasaponins 40 ~ 50 weight part, pregelatinized Starch 30 ~ 40 weight part, sodium starch glycolate 50 ~ 60 weight part in described Qiyeshen an dispersible tablet, silicon-dioxide 60 ~ 70 weight part, croscarmellose sodium 10 ~ 14 weight part, Microcrystalline Cellulose 32 ~ 38 weight part, Magnesium Stearate 1 ~ 2 weight part.
11. is according to claim 8 containing ginsenoside Rb
3the pharmaceutical composition of crystalline compounds, it is characterized in that, containing Folium Notoginseng total arasaponins 30 ~ 50 weight part, pregelatinized Starch 30 ~ 50 weight part, Microcrystalline Cellulose 60 ~ 100 weight part, carboxymethylstach sodium 10 ~ 20 weight part, magnesium stearate 1 ~ 2 weight part in described Qiyeshen' and tablet.
12. is according to claim 11 containing ginsenoside Rb
3the pharmaceutical composition of crystalline compounds, it is characterized in that, containing Folium Notoginseng total arasaponins 40 ~ 50 weight part, pregelatinized Starch 40 ~ 50 weight part, Microcrystalline Cellulose 80 ~ 100 weight part in described Qiyeshen' and tablet, carboxymethylstach sodium 15 ~ 20 weight part, magnesium stearate 1.5 ~ 2 weight part.
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| CN201410323946.1A CN104119416B (en) | 2014-07-08 | 2014-07-08 | A kind of ginsenoside Rb 3compound and containing the Qiyeshen an dispersible tablet of this compound and Qiyeshen' and tablet |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1615896A (en) * | 2003-11-12 | 2005-05-18 | 云南省药物研究所 | Medicine for regulating blood fat and treating cardiocerehral disease and preparing method |
| CN102775460A (en) * | 2011-12-21 | 2012-11-14 | 吉林大学 | Application of ginsenoside Rb3 in preparation of medicine for preventing and curing myocardial remodeling |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1615896A (en) * | 2003-11-12 | 2005-05-18 | 云南省药物研究所 | Medicine for regulating blood fat and treating cardiocerehral disease and preparing method |
| CN102775460A (en) * | 2011-12-21 | 2012-11-14 | 吉林大学 | Application of ginsenoside Rb3 in preparation of medicine for preventing and curing myocardial remodeling |
Non-Patent Citations (1)
| Title |
|---|
| 七叶神安分散片的制备工艺研究;黄瑞平 等;《中草药》;20091031;第40卷(第10期);第附1-2页 * |
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Address after: 323000 Zhejiang Province, Lishui City Economic Development Zone Shuige Industrial Zone Patentee after: ZHEJIANG WEIKANG PHARMACEUTICAL CO., LTD. Address before: 323000 Zhejiang Province, Lishui City Economic Development Zone Shuige Industrial Zone Patentee before: Zhejiang Wecome Medicine lndustry Co., Ltd. |