CN103462899B - A kind of Wuweizisu B solid dispersion and its preparation method and preparation - Google Patents
A kind of Wuweizisu B solid dispersion and its preparation method and preparation Download PDFInfo
- Publication number
- CN103462899B CN103462899B CN201310360501.6A CN201310360501A CN103462899B CN 103462899 B CN103462899 B CN 103462899B CN 201310360501 A CN201310360501 A CN 201310360501A CN 103462899 B CN103462899 B CN 103462899B
- Authority
- CN
- China
- Prior art keywords
- wuweizisu
- solid dispersion
- preparation
- present
- tablet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Abstract
The present invention provides a kind of Wuweizisu B solid dispersion and its preparation method, and the pharmaceutical preparation containing this solid dispersion. Described Wuweizisu B solid dispersion take mass ratio as the Wuweizisu B of 1:2��8 and polyvidone for main raw material obtains according to solvent method or polishing. The Wuweizisu B solid dispersion obtain the present invention and preparation thereof carry out dissolution in vitro, DSC, XRD check and stability test result shows in the solid dispersion that Wuweizisu B is openly prepared in the present invention with amorphous or molecularity exists, substantially increase its dissolution in vitro, the preparation stabilization that is prepared into, it is to increase the bioavailability that Wuweizisu B is oral.
Description
(1) technical field
The present invention relates to a kind of Wuweizisu B solid dispersion and its preparation method, and the pharmaceutical preparation containing this solid dispersion.
(2) background technology
Wuweizisu B (SchisandrinB, SchB) Magnoliacea plant is mainly come from, such as Magnoliaceae shizandra berry (Schisandrachinensis (Turcz.) Baill), Magnoliaceae schisandra chinensis (SchisandrasphenantheraRehd.etWils.), Magnoliaceae Schisandra chinensis (SchisandrachinensisBaill), it is also possible to synthetic. Lignan component is the primary medicinal component of shizandra berry, mainly has antitumor, antiviral, guarantor liver, the anti-ageing effect of waiting for a long time. The research of lignanoid, as one of the main active ingredient of shizandra berry lignanoid, is received much concern by Wuweizisu B with people. Recent study shows, Wuweizisu B has pharmacological actions such as protecting liver, anticancer, antiulcer agent. Also have document report Wuweizisu B to reverse in recent years resistance that P mono-gP mediates is such that it is able to for the treatment (Li Ling etc., the research of the tumor multi-drug resistance reversal effect that MRP is mediated by Wuweizisu B) of tumour; CN200410059607 also discloses the application of Wuweizisu B in oncotherapy. And Wuweizisu B extracting solution all has certain restraining effect (Li Bin etc., the research of Schisandra chinensis B prime scavenging free radicals and external bacteriostatic action) to free radical scavenging successful and to streptococcus aureus, Candida albicans, Salmonellas, intestinal bacteria, subtilis.
But research finds that Wuweizisu B is soluble in chloroform, ethanol, methyl alcohol, acetone and other organic solvent, it is difficult to being dissolved in water, oral availability is very low, cause the actual taking dose of patient big, increase side effect potentially. The solubleness or the dissolution rate that improve Wuweizisu B can improve the bioavailability of medicine in body, thus reach the object of attenuation synergistic, but there is no the measure that document report increases Wuweizisu B solubleness or dissolution rate so far.
(3) summary of the invention
In order to improve dissolution rate, the bioavailability of Wuweizisu B, the present invention provides a kind of Wuweizisu B solid dispersion and its preparation method, and the pharmaceutical preparation containing this solid dispersion.
The technical solution used in the present invention is:
A kind of Wuweizisu B solid dispersion take mass ratio as the Wuweizisu B of 1:2��8 and polyvidone for main raw material obtains. Said components is prepare solid dispersion main raw material used, does not comprise other auxiliary materials used in preparation process, such as solvent used time prepared by solvent method, or synergist used time prepared by polishing.
Solid dispersion is a kind of technique means improving insoluble drug dissolution rate and bioavailability. In solid dispersion, insoluble drug molecule is distributed in the solid support material of high molecular with amorphous form. But to different medicines, it is necessary to screened by solid dispersion solid support material, and it is prepared into solid dispersion according to the solid support material filtered out by suitable preparation method. It is multiple that solid dispersion solid support material conventional in prior art comprises sucrose, Citric Acid, urea, polyoxyethylene glycol, polyvidone etc., and the dispersion effect difference of these solid support materials in the solid dispersion of different pharmaceutical is very big. The present invention selects polyvidone as carrier, substantially increase its dissolution in vitro, the preparation stabilization being prepared into, it is to increase the bioavailability that Wuweizisu B is oral.
Preferably, Wuweizisu B and polyvidone mass ratio are 1:3��4.
In the present invention, polyvidone is preferably PVP K30 (PVP-K30).
The preparation method of Wuweizisu B solid dispersion comprises solvent method and polishing. In order to avoid the use of a large amount of organic solvent, the preferred polishing of the present invention, Ginding process used is unrestricted, and industrial conventional Ginding process all can be used for the present invention.
Preparing a method for described solid dispersion, described method comprises: Wuweizisu B and polyvidone are fully dissolved in organic solvent, reclaims organic solvent, dry, obtains described Wuweizisu B solid dispersion; Described organic solvent is one of following or wherein two or more mixture: ethanol, methyl alcohol, acetone, acetonitrile, tetrahydrofuran (THF), methylene dichloride, trichloromethane, ethyl acetate. In above-mentioned dissolution process, can heating to accelerate dissolution rate, the temperature of heating is at 30��85 DEG C. In this preparation method, the Solvent drying processes adopted is unrestricted, industrial conventional drying means such as drying under reduced pressure, spraying dry, constant pressure and dry preparation method all used in the present invention.
Preferably, described organic solvent is ethanol, and consumption is 100��200mL/g Wuweizisu B.
Preparing a method for described solid dispersion, described method comprises: Wuweizisu B, polyvidone is mixed, is placed in grinding in ball grinder, reclaims powder, obtains described Wuweizisu B solid dispersion. Polishing can reduce the application of organic solvent in a large number, greatly reduces production cost, it is to increase production security, and reaches the solubilizing effect identical with solvent method.
Preferably, being also added with synergist in process of lapping, a small amount of grinding synergist can avoid a large amount of uses of organic solvent, described synergist to be one of following: propylene glycol, glycerol, polyoxyethylene glycol, addition is 0.2��1.0mL/g Wuweizisu B. Test shows, the organic solvents such as monohydroxy-alcohol, ketone and ether volatilize rapidly in process of lapping, long-time dispersion moistening effect can not be played, desirable solid dispersion can not be obtained, and water is because wettability difference and solvability to medicine are poor, grinding can not play desirable dispersion effect, therefore, the polyvalent alcohol such as preferred glycerol in polishing. Wuweizisu B solid dispersion result of extraction prepared by solvent method of the present invention and preferred polishing obviously improves.
More preferred, described synergist is glycerol, and addition is 0.5mL/g Wuweizisu B.
The present invention also relates to a kind of Wuweizisu B oral drug preparation, adds pharmaceutically acceptable carrier by Wuweizisu B solid dispersion according to claim 1, makes one of following formulation: capsule, tablet, granule, pulvis, pill.
Preferred formulation is Tablet and Capsula agent, the preferred direct powder compression preparation of tablet.
The useful effect of the present invention is mainly reflected in: the Wuweizisu B solid dispersion obtain the present invention and preparation thereof carry out dissolution in vitro, DSC, XRD check and stability test result shows in the solid dispersion that Wuweizisu B is openly prepared in the present invention with amorphous or molecularity exists, substantially increase its dissolution in vitro, the preparation stabilization that is prepared into, it is to increase the bioavailability that Wuweizisu B is oral.
(4) accompanying drawing explanation
Fig. 1 is that different medicine prepared by solvent method carries the solid dispersion of ratio and the dissolution in vitro contrast of medicine and physical mixture;
Fig. 2 is that polishing prepares medicine load than being the solid dispersion of 1:3 and the dissolution in vitro contrast with medicine and physical mixture;
Fig. 3 is that the medicine load that polishing prepares different carriers compares than the external stripping of solid dispersion for 1:3;
Fig. 4 is the comparison of dissolution in vitro after the solid dispersion compressing tablet prepared of different methods;
Fig. 5 is sample DSC collection of illustrative plates;
Fig. 6 is sample XRD figure spectrum.
(5) embodiment
Below in conjunction with specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in this:
Embodiment 1: solvent method prepares Wuweizisu B/PVP solid dispersion
Measure 500ml ethanol, add 15g 30 POVIDONE K 30 BP/USP 90 wherein and fully vibrate dissolving. Then adding Wuweizisu B 5g, add and revolve steaming instrument, concentrate and substantially volatilize to solvent, quenching, dry, 80 order sieves pulverized by gained solid, obtained solid dispersion of the present invention.
Embodiment 2: solvent method prepares Wuweizisu B/PVP solid dispersion
Measure 500ml ethanol, add 20g 30 POVIDONE K 30 BP/USP 90 wherein and fully vibrate dissolving. Then adding Wuweizisu B 5g, add and revolve steaming instrument, concentrate and substantially volatilize to solvent, quenching, dry, 80 order sieves pulverized by gained solid, obtained solid dispersion of the present invention.
Embodiment 3: solvent method prepares Wuweizisu B/PVP solid dispersion
Measure 500ml ethanol, add 30g 30 POVIDONE K 30 BP/USP 90 wherein and fully vibrate dissolving. Then adding Wuweizisu B 5g, add and revolve steaming instrument, concentrate and substantially volatilize to solvent, quenching, dry, 80 order sieves pulverized by gained solid, obtained solid dispersion of the present invention.
Embodiment 4: polishing prepares Wuweizisu B/PVP solid dispersion
Taking Wuweizisu B 5g, PVP-K3015g, equivalent incremental method is crossed 80 order sieves and is mixed, and adds in ball mill, grinds about 2 hours, sampling, and gained powder crosses 80 order sieves, obtains solid dispersion of the present invention.
Embodiment 5: be that synergist polishing prepares Wuweizisu B/PVP solid dispersion taking glycerol
Taking Wuweizisu B 5g, PVP-K3015g, equivalent incremental method is crossed 80 order sieves and is mixed, and adds glycerol 2.5ml, adds in ball mill, grind 2 hours, sampling, and gained powder crosses 80 order sieves, obtains solid dispersion of the present invention.
Embodiment 6(comparative example): it is that synergist polishing prepares Wuweizisu B/PVP solid dispersion taking water
Taking Wuweizisu B 5g, PVP-K3015g, equivalent incremental method is crossed 80 order sieves and is mixed, and adds water 2.5ml, adds in ball mill, grinding certain time, sampling, oven drying, and gained powder crosses 80 order sieves, obtains solid dispersion.
Embodiment 7(comparative example): the preparation of Wuweizisu B/PVP physical mixture
Taking Wuweizisu B 5g, PVP-k3015g equivalent incremental method is crossed 80 order sieves and is mixed and get final product.
Embodiment 8: the preparation of Wuweizisu B/PVP solid dispersion tablet
The solid dispersion taking embodiment 1,5,7 respectively according to prescription mixes with the MCC102 crossing 80 order sieves, CCNa, micropowder silica gel, by every sheet 50mg Wuweizisu B direct compression, obtains tablet of the present invention.
Embodiment 9(comparative example): polishing prepares Wuweizisu B/PEG solid dispersion
Taking Wuweizisu B 5g, PEG600015g, equivalent incremental method is crossed 80 order sieves and is mixed, and adds in ball mill, grinds about 2 hours, sampling, and gained powder crosses 80 order sieves, obtains solid dispersion.
Embodiment 10:
(1) external stripping experiment
Measure the external stripping of each sample such as embodiment 1��9 and Wuweizisu B drug powder respectively.
Dissolution in vitro experiment measures according to the paddle method of regulation in " Chinese Pharmacopoeia " (2010 editions two) annex. Rotating speed is 50r/min, and thermostatic is at 37 �� 0.5 DEG C, and dissolution medium is 0.25%SLS900ml. Precision takes solid dispersion (being equivalent to 50mg Wuweizisu B) or gets solid dispersion tablet, directly it is placed in stripping rotor, namely timing is started, 10ml is sampled respectively at certain time, supplementing isothermal equal-volume dissolution medium immediately, filtrate, after 0.45um filtering with microporous membrane, is diluted to suitable concentration, measure absorbance A in wavelength 254nm, calculate Accumulation dissolution (%). The results are shown in Figure 1��Fig. 4.
Result shows, the release in vitro of solid dispersion prepared by solvent method and polishing is obviously faster than physical mixture, and solid dispersion prepared by solvent method, medicine load is than for more stable during 1:3 or 1:4, more PVP can not improve the stability (Fig. 1��Fig. 2) of solid dispersion; The solid dispersion release adding synergist grinding preparation is better than the solid dispersion (Fig. 3) not added; The solid dispersion release that PVP-k30 is prepared as carrier polishing is better than PEG6000(Fig. 4).
(2) DSC test
Laboratory sample: embodiment 1,4,5,6,7,8, and Wuweizisu B powder and PVP-k30.
Getting appropriate amount of sample powder, carry out thermal analyses with thermal analyzer, record its DSC collection of illustrative plates, the DSC curve of contrast solvent method, polishing, physical mixture, medicine, carrier, the results are shown in Figure 5.
Result display Wuweizisu B has the melting peak of medicine at about 120 DEG C, and physical mixture also observes the melting peak of medicine at about 120 DEG C. Solid dispersion prepared by embodiment 1 solvent method and embodiment 5 polishing add in the collection of illustrative plates of synergist and find that melting peak disappears, and tentatively can conclude that medicine is scattered in carrier with amorphous or molecular conformation, define good solid dispersion. The melting peak that can observe medicine in embodiment 8 physical mixture diminishes, but does not disappear, it is possible to illustrates or has the medicine of crystal type to be present in solid dispersion.
(3) XRD test
Laboratory sample: embodiment 1,4,5,6,7,8, and Wuweizisu B powder and PVP-k30.
Getting appropriate amount of sample powder, record X ray diffracting spectrum, the DSC curve of contrast solvent method, polishing, physical mixture, medicine, carrier, the results are shown in Figure 6.
Result display Wuweizisu B has obvious peak crystallization, and physical mixture is as the same. Solid dispersion prepared by embodiment 1 solvent method and embodiment 5 polishing add in the collection of illustrative plates of synergist and find that peak crystallization disappears, and in conjunction with DSC result it can be shown that medicine is scattered in carrier with amorphous or molecular conformation, define good solid dispersion. The peak crystallization that can observe medicine in embodiment 8 physical mixture diminishes, but does not disappear, it is possible to illustrates or has the medicine of crystal type to be present in solid dispersion.
(4) tablet stability test
Laboratory sample: embodiment 8 gained tablet.
Get some, tablet, it is placed in clean Glass Containers, respectively at 60 DEG C, 25 DEG C, RH90% �� 5%, placed 10 days when lighting box (illumination 4500Lx �� 500Lx), at the 5th day and the 10th day sampling detection dissolution rate, comparing with 0 day, dissolution test method is with (1).
The results are shown in following table:
Table 1: stability test stripping result
Result visible embodiment 8 gained tablet transfers postpone three kinds of violent conditions, and the outward appearance of tablet does not change, and the stripping of 30min all remains on about 100%, and therefore the solid dispersion tablet of the present invention is to high temperature, and high wet, high light is stablized.
(5) tablet biotinylated biomolecule availability comparative experiments
1. research purpose
After investigating the oral two kinds of Wuweizisu B tablets of Beagle dog, plasma pharmacokinetics parameter, calculates and compares both bioavailabilities.
2. instrument and material
2.1 main instruments
Power & light company of U.S. Finnigan high performance liquid chromatography quadrupole rods tandem mass spectrometry combined instrument (containing FinniganSurveyor highly effective liquid phase chromatographic system, FinniganTSQQuantumDiscoverymax mass spectrometer system, electric spray ion source, Xcalibur1.2 workstation and LCQuan data processing software).
GENIEVORTEX-2 vortex mixed device; EPPENDORF high speed freezing centrifuge; Milli-QGradientA1 ultrapure water machine (MilliporeInc, USA).
2.2 reagent
Acetonitrile is chromatographically pure, provides by Fisher company; T-butyl methyl ether is chromatographically pure; All the other reagent are domestic analytical pure.
Tablet one (Tablet1): embodiment 8 gained tablet;
Tablet two (Tablet2): Wuweizisu B solid dispersion is replaced for Wuweizisu B, according to the tablet that embodiment 8 method is obtained.
3. in blood plasma, Wuweizisu B LC-MS/MS method is reappeared
3.1 chromatograms and Mass Spectrometry Conditions
Liquid phase chromatogram condition: chromatographic column: AgilentZORBAXExtend-C18(3.5 ��m, 50mm �� 2.1mmI.D.); Moving phase: gradient elution, in table 2, working time 3.5min; Flow velocity: 0.2ml/min; Sample size: 5 �� l; Post temperature: room temperature.
Table 2: liquid chromatography gradient elution table
| Time (min) | Water % | Acetonitrile % |
| 0 | 20 | 80 |
| 2.2 | 20 | 80 |
| 2.3 | 0 | 100 |
| 3.0 | 0 | 100 |
| 3.1 | 20 | 80 |
| 3.5 | 20 | 80 |
Mass Spectrometry Conditions: ionization mode: electro-spray ionization (ESI); Acquisition mode: selective reaction monitoring (SRM); SprayVoltage(spray voltage) 4600V; Capillarytemperature (capillary temperature) 300 DEG C, sheath gas (N2) flow velocity 30Arb, auxiliary gas (N2) flow velocity 10Arb. Detection ion: Wuweizisu B 401.1-300.0m/z, interior mark (deoxyschizandrin) 417.2-316.0m/z, collision voltage is respectively 21 and 27v.
The preparation of 3.2 contrast solutions
The preparation of Wuweizisu B contrast solution: precision takes Wuweizisu B highly finished product 5.0mg, to, in 10ml measuring bottle, holding so that chromatogram dissolve with methanol is also fixed, obtain the Wuweizisu B stock solution of 0.5mg/mL, before use by dilution in acetonitrile to desired concn.
The preparation of interior mark contrast solution: precision takes deoxyschizandrin reference substance 5.0mg, puts in 10ml measuring bottle, surely holds with chromatogram dissolve with methanol, is mixed with and is equivalent to the stock solution that deoxyschizandrin is about 0.5mg/mL, faces the used time with dilution in acetonitrile to desired concn.
3.3 plasma sample process
Precision pipettes Beagle dog plasma 100 �� L, puts in dorf pipe, adds 2.5 �� g/ml inner mark solution 10ul. Add Extraction solvent t-butyl methyl ether 1.0mL, vortex vibration 3min, mixed even, the centrifugal 1min of 13000rpm, precision pipettes supernatant liquid 0.9mL and puts in another dorf pipe, vacuum is drained, residue adds acetonitrile 100 �� L, and vortex DL is dissolved, after the centrifugal 10min of 13000rpm, get supernatant liquor and carry out LC-MS/MS analysis, record color atlas. Quantitative analysis is carried out with determinand peak area and interior mark peak area ratio.
3.4 typical curve preparations
Plasma concentration is selected: 5,10,20,50,100,200,500,1000,2000,5000ng/ml. Compound method: precision pipettes blank Beagle dog plasma 90 �� L, puts in EP pipe, adds a series of concentration working fluid 10 �� l and inner mark solution 10 �� l(IS blood plasma final concentration 0.25ug/ml), remaining steps is with " 3.3 " item.
3.5 quality-control sample preparations
Quality-control sample concentration is selected: 10,100,1000,4000ng/ml. Treatment process is with " 3.4 " item.
4. bioavailability study in Beagle dog body of two kinds of preparations
4.1 experimental design
Adopting two cycle dual crossing scheme, totally three Beagle dogs, two kinds of tablets, every dog is to the corresponding tablet of a slice. Blood sampling time point is as follows: 20min, 40min, 1,2,3,4,6,8,12,24h. Gather blank blood before administration, dog upper limbs venous blood collection, anticoagulant heparin, shift whole upper plasma after the blood essence centrifugal 10min of 4000rpm and deposit pipe ,-40 DEG C of preservations to standby. First and second cycle experimental date is respectively on September 27th, 2011 and on October 8th, 2011.
4.2 plasma sample processing modes are with 3.3
5. result
Through measuring the Plasma Concentration of two cycle Wuweizisu Bs in Beagle dog body, arrangement data and pharmacokinetic parameter are such as table 3 and 4. Finding that tablet one bioavailability is obviously higher than tablet two by comparing, about 3-4 is doubly.
: table 3:Beagle dog record after giving Tablet1 through time plasma drug level (ng/ml) and pharmacokinetic parameter
ND: lower than minimal detectable concentration
Table 4:Beagle dog record after giving Tablet2 through time plasma drug level (ng/ml) and pharmacokinetic parameter
Can calculate the bioavailability difference of these two kinds of tablets by comparing the AUC of two kinds of prescription tablets, the bioavailability of tablet one is 9 times of tablet two respectively.
Claims (1)
1. prepare the method for Wuweizisu B solid dispersion for one kind, it is characterized in that described method comprises: Wuweizisu B, PVP K30 are mixed, it is placed in grinding in ball grinder, reclaim powder, obtaining described Wuweizisu B solid dispersion, described Wuweizisu B and polyvidone mass ratio are 1:3��4, are also added with synergist in process of lapping, described synergist is glycerol, and addition is 0.5mL/g Wuweizisu B.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310360501.6A CN103462899B (en) | 2013-05-20 | 2013-08-16 | A kind of Wuweizisu B solid dispersion and its preparation method and preparation |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310188766 | 2013-05-20 | ||
| CN2013101887662 | 2013-05-20 | ||
| CN201310188766.2 | 2013-05-20 | ||
| CN201310360501.6A CN103462899B (en) | 2013-05-20 | 2013-08-16 | A kind of Wuweizisu B solid dispersion and its preparation method and preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103462899A CN103462899A (en) | 2013-12-25 |
| CN103462899B true CN103462899B (en) | 2016-06-01 |
Family
ID=49788100
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310360501.6A Active CN103462899B (en) | 2013-05-20 | 2013-08-16 | A kind of Wuweizisu B solid dispersion and its preparation method and preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103462899B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1747720A (en) * | 2003-02-03 | 2006-03-15 | 诺瓦提斯公司 | Pharmaceutical formulation |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101292981A (en) * | 2007-04-29 | 2008-10-29 | 杨喜鸿 | Solid dispersion, composition of rimonabant, preparation and medicament application thereof |
-
2013
- 2013-08-16 CN CN201310360501.6A patent/CN103462899B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1747720A (en) * | 2003-02-03 | 2006-03-15 | 诺瓦提斯公司 | Pharmaceutical formulation |
Non-Patent Citations (1)
| Title |
|---|
| 五仁醇固体分散体的制备及体外溶出度研究;赵铁等;《中草药》;20050731;第36卷(第7期);998-1002 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103462899A (en) | 2013-12-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101543476B (en) | A naringin solid dispersion and the preparation method, and the application thereof | |
| Kukula-Koch et al. | Application of pH-zone refining hydrostatic countercurrent chromatography (hCCC) for the recovery of antioxidant phenolics and the isolation of alkaloids from Siberian barberry herb | |
| CN103145677B (en) | Method for separating active ingredients from aquilaria sinensis lamina by utilizing high-speed countercurrent chromatography | |
| CN102920674B (en) | Technology for preparing hydroxychloroquine sulfate tablets | |
| CN104739751A (en) | Tetrahydrocurcumin solid dispersion and preparation method thereof | |
| Li et al. | Characterization of chemical constituents in Shuanghuanglian oral dosage forms by ultra‐high performance liquid chromatography coupled with time‐of‐flight mass spectrometry | |
| Liu et al. | Poly‐pharmacokinetic strategy represented the synergy effects of bioactive compounds in a traditional Chinese medicine formula, Si Shen Wan and its separated recipes to normal and colitis rats | |
| CN105911192B (en) | A kind of extracting method and fingerprint atlas detection method of Pterospermi Heterophylli active site promoting blood circulation and removing blood stasis | |
| CN103462899B (en) | A kind of Wuweizisu B solid dispersion and its preparation method and preparation | |
| CN110638768B (en) | Preparation method of medicine for treating male erectile dysfunction | |
| CN109053756B (en) | Phenylpropanoid ester type catechin and preparation method and application thereof | |
| CN104721158A (en) | Stable everolimus tablet | |
| Xu et al. | Preparation of evodiamine solid dispersions and its pharmacokinetics | |
| CN102190692A (en) | Preparation method and medical purpose of novel dihydro-flavonoid | |
| Wong et al. | Comprehensive quantitative analysis of Chinese patent drug YinHuang drop pill by ultra high-performance liquid chromatography quadrupole time of flight mass spectrometry | |
| CN103301081A (en) | Cefdinir dispersible tablet and preparation method thereof | |
| CN104297360B (en) | A kind of detection method of Compound Xueshuantong preparation finger-print | |
| CN105535515A (en) | Application of Lvji cough asthma tablets to preparation of medicine for inhibiting cell proliferation of prostate cancer cells PC-3 | |
| Jin et al. | Simultaneous determination of triptolide, tripdiolide and tripterine in human urine by high‐performance liquid chromatography coupled with ion trap atmospheric‐pressure chemical ionization mass spectrometry | |
| CN104274440B (en) | Andrographolide composite particles and preparation method thereof | |
| CN102558276B (en) | Non-sizing pipecuronium and preparation method and purpose thereof | |
| CN108469487B (en) | Method for measuring content of alderone in katsumadai seed | |
| Alali et al. | LC-MS and LC-PDA vs. phytochemical analysis of Colchicum brachyphyllum | |
| CN1883493B (en) | Solid-state molecular dispersible preparation of pennogenin compound | |
| Kartbaeva et al. | Compositional study of phenolic compounds of Cistanche salsa (CA Mey) G. Beck, growing in the Republic of Kazakhstan |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |