CN101897677A - Imperatorin sustained release tablets and preparation method thereof - Google Patents
Imperatorin sustained release tablets and preparation method thereof Download PDFInfo
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Abstract
The invention discloses imperatorin sustained release tablets and a preparation method thereof. The imperatorin sustained release tablets comprise the following components in percentage by mass: 10.0 to 20.0 percent of imperatorin, 10.0 to 20.0 percent of sustained release medium and the balance of auxiliary material. The sustained release medium is one or more of hydroxypropyl methyl cellulose, polyvinylpyrrolidone, carbomer, sodium carboxymethylcellulose, methylcellulose and ethylcellulose. The imperatorin sustained release tablets provided by the invention can be used for treating hypertension disease. The imperatorin and the sustained release medium are proportioned, therefore the imperatorin can be released in the sustained release medium slowly and stably so as to fulfill the aim of controlling the release rate of the imperatorin.
Description
Technical field
The present invention relates to the biological medicine technology field, relate to a kind of novel form of imperatorin, particularly a kind of imperatorin sustained release tablets and preparation method thereof.
Background technology
Cardiovascular and cerebrovascular disease is the commonly encountered diseases of a kind of serious threat mankind's life and health, particularly mid-aged population more than 50 years old.Cardiovascular and cerebrovascular disease has characteristics such as " sickness rate height, disability rate height, mortality rate height, relapse rate height, complication are many ".According to statistics, every year is died from the number of cardiovascular and cerebrovascular disease up to 1,500 ten thousand in the whole world, occupies various causes of the death first place.No matter the medicine of autonomous research and development treatment cardiovascular and cerebrovascular disease is for safeguarding human life and health, still all being significant for creating social benefit and economic benefit aspect.
Imperatorin is one of main component of coumarin kind compound in the Chinese medicine Radix Angelicae Dahuricae, the Fructus Cnidii, its molecular formula: C
16H
14O
4, molecular weight: 270.28, chemical structural formula is:
The Chinese patent publication number is that the document of CN1973835A discloses the medicinal usage that imperatorin is used to prepare resisting cardiovascular disease.It is experimental model that this patent of invention adopts rat aorta ring, rat mesenteric artery, people's omentum majus tremulous pulse respectively, having investigated imperatorin is the diastole effect of tremulous pulse, people's omentum majus tremulous pulse to rat aorta, rat intestine, and the effect of vascular smooth muscle in imperatorin vasodilator effect.Proved that Imperatoria ostruthium have tangible vasodilative effect, and proved conclusively mainly vasodilatory mechanism of imperatorin by stream and the release of interior calcium in the outer calcium of inhibition voltage dependence calcium channel and the calcium channel mediation of receptor intermediary.This patent is that imperatorin is applied to clinical pharmacology, the pharmacodynamics basis of having established as antihypertensive drug.
Need medication characteristics long-term, frequent drug administration, its medicine slow releasing preparation that is developed to preferably at hypertension.Slow releasing preparation can make medicine slowly discharge with given pace, can keep active drug concentration in the body for a long time, is a kind of faster dosage form of development in recent years.And at present as the slow releasing preparation of effective ingredient report is not arranged also with imperatorin.
Summary of the invention
The problem that the present invention solves is to provide a kind of imperatorin sustained release tablets and preparation method thereof, rate of release with the control imperatorin, prepared imperatorin sustained release tablets can slowly in release medium, stable discharge medicine, keeps comparatively stable blood concentration and longer action time.
The present invention realizes by following scheme:
A kind of imperatorin sustained release tablets in mass fraction, comprises 10.0～20.0% imperatorin and 10.0～20.0% slow release medium, and all the other are adjuvant; Described slow release medium is one or more in the middle of hydroxypropyl emthylcellulose (HPMC), polyvinylpyrrolidone (PVP), carbomer (Carbomer), sodium carboxymethyl cellulose (CMC-Na), methylcellulose (MC), the ethyl cellulose (EC).
Described imperatorin sustained release tablets, comprise 12.0～16.7% imperatorin and 12.0～17.0% slow release medium, described slow release medium is two kinds in the middle of hydroxypropyl emthylcellulose, polyvinylpyrrolidone, carbomer, methylcellulose, the ethyl cellulose.
Described adjuvant is made up of diluent, lubricant and binding agent, wherein, the mass fraction that diluent accounts for imperatorin sustained release tablets is 65.7～78.7%, the mass fraction that lubricant accounts for imperatorin sustained release tablets is 1.0～1.8%, and the mass fraction of binder constitutes imperatorin sustained release tablets is 0.3～1.0%.
Described diluent is one or both in the middle of lactose, starch, the dextrin.
Described lubricant is Pulvis Talci or magnesium stearate.
A kind of preparation method of imperatorin sustained release tablets may further comprise the steps:
1) mixing diluents with 10.0～20.0% imperatorin, 5.0～10.0% slow release medium and 65.7～78.7% is even, ratio according to imperatorin/binding agent=10g/2～10mL adds binding agent then, and fully wet granulation obtains wet granular behind the mixing;
2) wet granular being dried to moisture mass fraction under 50～60 ℃ is 1.0～3.0%, obtains dried granule;
3) dried granule is crossed 24 mesh sieve granulate after, with the slow release medium of dried granule and 5.0～10.0% and 1.0～1.8% the abundant mixing of lubricant, tabletting is made imperatorin sustained release tablets then again.
Described slow release medium is one or more in the middle of hydroxypropyl emthylcellulose, polyvinylpyrrolidone, carbomer, methylcellulose, the ethyl cellulose; Described diluent is one or both in the middle of lactose, starch, the dextrin; Described lubricant is Pulvis Talci or magnesium stearate.
Described binding agent is that volumetric concentration is that 60% ethanol, mass concentration are 0.5～3% CMC-Na aqueous solution or PVP-ethanol-water solution; Described PVP-ethanol-water solution is that PVP is dissolved in volumetric concentration is that the mass concentration of PVP is 5～15% in the gained solution in 75% the ethanol-water solution.
The described slow release medium of described step 1) is hydroxypropyl emthylcellulose, methylcellulose, ethyl cellulose; Step 2) described slow release medium is polyvinylpyrrolidone or carbomer.
Compared with prior art, the present invention has following beneficial technical effects:
Imperatorin sustained release tablets provided by the present invention can be used for the treatment of high blood pressure disease.Prepared imperatorin sustained release tablets is by the proportioning of imperatorin and slow release medium, makes the release that imperatorin is can be in the slow release medium slow, stable, reached the purpose of the rate of release of control imperatorin.External, the effective ingredient imperatorin burst size after 3 hours in the middle of the imperatorin sustained release tablets is that burst size is that burst size is 80%～100% of a total amount behind 50%～70%, 12 hours of total amount behind 20%～40%, 6 hours of total amount.In vivo, the peak reaching time of blood concentration (T of conventional tablet
Max) be 1.7h, maximum plasma concentration (C
Max) be 0.86 μ g/mL, the half-life only is 1.9h; And curve there is no tangible peak valley phenomenon during the slow releasing tablet medicine, and drug absorption slows down, and slowly reaches the peak, and peak concentration obviously reduces, T
MaxBe 3.2h, C
MaxBe 0.37 μ g/mL.The elimination half-life is 3.336h, and relative bioavailability is 127.25%.
Compare with the imperatorin conventional tablet, imperatorin sustained release tablets can by medicine stable, slowly discharge, reduce the blood drug level peak value, keep than stable blood concentration prolong drug action time.Imperatorin sustained release tablets can better solve hypertension needs medication problem long-term, frequent drug administration, and it is convenient that the patient takes imperatorin sustained release tablets: oral, and the 1-2 sheet/time, 2 times/day, can divide sooner or later and take for twice.
Description of drawings
Fig. 1 is imperatorin sustained release tablets and imperatorin ordinary tablet blood plasma kinetic curve to such as figure; Wherein abscissa is that sample time, (unit: h), vertical coordinate was the (unit: μ g/mL) of imperatorin concentration in the plasma sample.
The specific embodiment
The invention provides a kind of imperatorin sustained release tablets and preparation method thereof, rate of release with the control imperatorin, prepared imperatorin sustained release tablets can slowly in release medium, stable discharge effective ingredient, keeps comparatively stable blood concentration and longer action time.The invention will be further described to detect example below in conjunction with embodiment and drug release, and the explanation of the invention is not limited.
Embodiment 1
The preparation method of imperatorin sustained release tablets may further comprise the steps:
1) imperatorin crude drug and each adjuvant are crossed 80 mesh sieves, the lactose that takes by weighing the HPMC-100M of imperatorin, 15g of 50g and 206g respectively mixes and stirs, ratio according to imperatorin/binding agent=10g/3mL adds 15% (wt) PVP-ethanol-water solution (75%) 15mL then, fully cross 24 mesh sieves behind the mixing, wet granulation obtains wet granular;
2) wet granular being dried to moisture mass fraction under 60 ℃ is 3.0%, obtains dried granule;
3) dried granule is crossed 24 mesh sieve granulate after, with the carbomer 934 NF of dried granule and 24g and the abundant mixing of magnesium stearate of 5g, be pressed into 1000 then again, make imperatorin sustained release tablets.
In the middle of the made imperatorin sustained release tablets, in mass fraction, imperatorin is 16.6%, HPMC-100M is 5%, carbomer 934 NF is 8%, lactose is 68.2%, magnesium stearate is 1.6%.
Embodiment 2
The preparation method of imperatorin sustained release tablets may further comprise the steps:
1) imperatorin crude drug and each adjuvant are crossed 80 mesh sieves, the starch that takes by weighing the HPMC-15M of imperatorin, 24g of 50g and 206g respectively mixes and stirs, ratio according to imperatorin/binding agent=10g/2mL adds 10% (wt) PVP-ethanol-water solution (75%) 10mL then, fully cross 24 mesh sieves behind the mixing, wet granulation obtains wet granular;
2) wet granular being dried to moisture mass fraction under 60 ℃ is 3.0%, obtains dried granule;
3) dried granule is crossed 24 mesh sieve granulate after, with the carbomer 934 NF of dried granule and 15g and the abundant mixing of Pulvis Talci of 5g, be pressed into 1000 then again, make imperatorin sustained release tablets.
In the middle of the made imperatorin sustained release tablets, in mass fraction, imperatorin is 16.6%, HPMC-15M is 8%, carbomer is 5%, starch is 68.2%, magnesium stearate is 1.6%.
Embodiment 3
The preparation method of imperatorin sustained release tablets may further comprise the steps:
1) imperatorin crude drug and each adjuvant are crossed 80 mesh sieves, the dextrin that takes by weighing the HPMC-4M of imperatorin, 30g of 50g and 200g respectively mixes and stirs, ratio according to imperatorin/binding agent=10g/2mL adds 60% ethanol 10mL then, fully cross 24 mesh sieves behind the mixing, wet granulation obtains wet granular;
2) wet granular being dried to moisture mass fraction under 50 ℃ is 2.5%, obtains dried granule;
3) dried granule is crossed 24 mesh sieve granulate after, with the polyvinylpyrrolidone of dried granule and 15g and the abundant mixing of Pulvis Talci of 5g, be pressed into 1000 then again, make imperatorin sustained release tablets.
In the middle of the made imperatorin sustained release tablets, in mass fraction, imperatorin is 16.7%, HPMC-4M is 10%, polyvinylpyrrolidine is 5%, dextrin is 66.6%, Pulvis Talci is 1.6%.
Embodiment 4
The preparation method of imperatorin sustained release tablets may further comprise the steps:
1) imperatorin crude drug and each adjuvant are crossed 80 mesh sieves, the dextrin that takes by weighing the starch of ethyl cellulose, 100g of HPMC-4M, 15g of imperatorin, 15g of 50g and 100g respectively mixes and stirs, adding mass concentration according to the ratio of imperatorin/binding agent=10g/3mL then is 2% CMC-Na aqueous solution 15mL, fully cross 24 mesh sieves behind the mixing, wet granulation obtains wet granular;
2) wet granular being dried to moisture mass fraction under 55 ℃ is 2.0%, obtains dried granule;
3) dried granule is crossed 24 mesh sieve granulate after, with the polyvinylpyrrolidone of dried granule and 15g and the abundant mixing of Pulvis Talci of 5g, be pressed into 1000 then again, make imperatorin sustained release tablets.
In the middle of the made imperatorin sustained release tablets, in mass fraction, imperatorin is 16.6%, HPMC-4M is 5%, ethyl cellulose is 5%, polyvinylpyrrolidone is 5%, starch is 33.3%, dextrin is 33.3%, Pulvis Talci is 1.6%.
Embodiment 5
The preparation method of imperatorin sustained release tablets may further comprise the steps:
1) imperatorin crude drug and each adjuvant are crossed 80 mesh sieves, the dextrin that takes by weighing the lactose of ethyl cellulose, 200g of methylcellulose, the 10g of imperatorin, the 10g of 50g and 115g respectively mixes and stirs, ratio according to imperatorin/binding agent=10g/6mL adds 60% ethanol 30mL then, fully cross 24 mesh sieves behind the mixing, wet granulation obtains wet granular;
2) wet granular being dried to moisture mass fraction under 58 ℃ is 1.5%, obtains dried granule;
3) dried granule is crossed 24 mesh sieve granulate after, with the carbomer 934 NF of dried granule and 25g and the abundant mixing of Pulvis Talci of 5g, be pressed into 1000 then again, make imperatorin sustained release tablets.
In the middle of the made imperatorin sustained release tablets, in mass fraction, imperatorin is 12%, methylcellulose is 2.4%, ethyl cellulose is 2.4%, carbomer 934 NF is 6%, lactose is 48.1%, dextrin is 27.7%, Pulvis Talci is 1.2%.
Embodiment 6
The preparation method of imperatorin sustained release tablets may further comprise the steps:
1) imperatorin crude drug and each adjuvant are crossed 80 mesh sieves, the starch that takes by weighing the lactose of ethyl cellulose, 100g of HPMC-15M, 5g of imperatorin, 10g of 50g and 100g respectively mixes and stirs, adding mass concentration according to the ratio of imperatorin/binding agent=10g/3mL then is 0.5% CMC-Na aqueous solution 15mL, fully cross 24 mesh sieves behind the mixing, wet granulation obtains wet granular;
2) wet granular being dried to moisture mass fraction under 52 ℃ is 1.5%, obtains dried granule;
3) dried granule is crossed 24 mesh sieve granulate after, with the polyvinylpyrrolidone of dried granule and 30g and the abundant mixing of Pulvis Talci of 5g, be pressed into 1000 then again, make imperatorin sustained release tablets.
In the middle of the made imperatorin sustained release tablets, in mass fraction, imperatorin is 16.6%, HPMC-15M is 3.3%, ethyl cellulose is 1.7%, polyvinylpyrrolidone is 10%, lactose is 33.3%, starch is 33.3%, Pulvis Talci is 1.6%.
Embodiment 7
The preparation method of imperatorin sustained release tablets may further comprise the steps:
1) imperatorin crude drug and each adjuvant are crossed 80 mesh sieves, the lactose of CMC-Na, 190.5g that takes by weighing imperatorin, the 33.5g of 50g respectively mixes and stirs, ratio according to imperatorin/binding agent=10g/2mL adds 5%PVP alcoholic solution (75%) 10mL then, fully cross 24 mesh sieves behind the mixing, wet granulation obtains wet granular;
2) wet granular being dried to moisture mass fraction under 60 ℃ is 1.5%, obtains dried granule;
3) dried granule is crossed 24 mesh sieve granulate after, with the abundant mixing of the Pulvis Talci of dried granule and 5g, be pressed into 1000 then again, make imperatorin sustained release tablets.
In the middle of the made imperatorin sustained release tablets, in mass fraction, imperatorin is 17.9%, CMC-Na is 12%, lactose is 68.2%, Pulvis Talci is 1.8%.
Imperatorin sustained release tablets inside and outside release test
(1) the release in vitro degree is measured
Experimental technique: get prepared imperatorin sustained release tablets, measure with reference to Chinese Pharmacopoeia (2005 editions two ones) appendix XC second method.900mL is a release medium with 0.5%SDS phosphate-buffered (pH=7.4), handles, puts in the stripping rotor through the degassing, puts into the iron wire grid of 2 * 2cm simultaneously in stripping rotor, treats the release medium temperature constant at 37 ℃ ± 0.5 ℃, and rotating speed is 100 rev/mins.Get 6 of imperatorin sustained release tablets, drop into respectively in 6 stripping rotors, in 1,2,3,4,6,8,10, drew release medium 0.5mL in 12 hours, and added the fresh release medium of isothermal immediately, the release medium of drawing is filtered through 0.45 μ m filter membrane, get subsequent filtrate and carry out high-performance liquid chromatogram determination.The record peak area calculates the concentration of imperatorin in the release medium by external standard method, and calculates the accumulative total release rate of different sample times.
High-performance liquid chromatogram determination method: chromatographic column is Diamonsil C18 (150mm * 4.6mm, 5 μ m); Mobile phase: methanol-water (65: 35); Detect wavelength 302nm; Column temperature: 25 ℃; Flow velocity: 1.0mL/min.Theoretical cam curve should be not less than 3000 in the imperatorin peak.
Testing result: 6 imperatorin sustained release tablets, release rate is that release rate is that release rate is 80.98%～93.49% after 58.72%～70.39%, 12 hours after 26.10%～35.12%, 6 hours after 3 hours.Concrete testing result is as shown in table 1.
Table 1 imperatorin sustained release tablets release in vitro result
(2) blood plasma kinetic measurement in the Beagle dog body
Detection method: six of healthy beagle dogs, body weight 11.0-11.2kg, fasting 12h before taking medicine is divided into two groups at random, takes ordinary tablet earlier for one group, after take slow releasing tablet, took medicine for twice 7 days at interval, another group is taken slow releasing tablet earlier, after take ordinary tablet.Single dose intersects oral imperatorin sustained release tablets 1 (every contains imperatorin 50mg) and contrast 2 of ordinary tablets of imperatorin (every contains imperatorin 25mg), gets blank blood before the administration earlier, and ordinary tablet is in 0.5 after the administration, 1,1.25,1.5,2,2.5,3,4,6,8,10,12h, slow releasing tablet is in 1,2,3,4,6,8,10,12, the about 1.2mL of 24h foreleg small saphenous vein blood sampling places the centrifuge tube that scribbles heparin, under the 3000r/min condition, centrifugal 10min draws upper plasma immediately, place-20 ℃ of refrigerators to preserve, pending, analysis.
Plasma sample is handled: the accurate absorption in the Fructus Cnidii inner mark solution adding 10mL centrifuge tube that 5 μ L concentration are 5.3 μ g/mL, dry up the back and add the 0.5mL dog plasma, vortex 2 minutes adds extract (ethyl acetate: 2mL petroleum ether=1: 1), vortex 5min, centrifugal 10min (3000r/min) leaves standstill 30min, quantitatively draws organic layer 1.5mL, 40 ℃ of nitrogen dry up, add extract 100 μ L, vortex makes abundant dissolving, gets imperatorin concentration in the 1 μ L gas phase-mass spectrography working sample.
Gas phase-mass spectrum condition: gas phase condition: the Rtx-5MS (capillary gas chromatographic column of 30m * 0.25mm * 0.25um); With high-purity helium is carrier gas, flow velocity 2.0mL/min; Injector temperature: 280 ℃, input mode: split sampling not, temperature programming: 140 ℃ of initial temperatures, keep 2min, be warming up to 280 ℃ with 10 ℃/min speed, keep 4min, sample introduction is 1 μ L, 280 ℃ of interface temperature.The mass spectrum condition: 200 ℃ of EI source temperatures, electron bombard energy are 70eV, select ion detection at times, and when mensuration was imperatorin, it was 244 that 3min selects m/z to 12min, 12min during to 20min selection m/z be 202.
Testing result: the imperatorin ordinary tablet absorbs, eliminates all very fast, and curve display goes out tangible absworption peak during medicine.Peak time (T
Max) 1.7h, maximum plasma concentration (C
Max) be 0.86 μ g/mL, the half-life only is 1.9h.And curve there is no tangible peak valley phenomenon during the slow releasing tablet medicine, and drug absorption slows down, and slowly reaches the peak, and peak concentration obviously reduces.T
MaxBe 3.2h, C
MaxBe 0.37 μ g/mL.The elimination half-life is 3.336h.Relative bioavailability is 127.25%.Imperatorin sustained release tablets and the contrast of ordinary tablet blood plasma kinetic curve are as shown in Figure 1.
(3) compare with the imperatorin conventional tablet, imperatorin sustained release tablets can be by stable, the slowly release of medicine, repeatability is better, reduce the blood drug level peak value, keep, prolong drug action time than stable blood concentration, patient's taking convenience: oral, the 1-2 sheet/time, 2 times/day, can divide sooner or later and take for twice.
Claims (9)
1. an imperatorin sustained release tablets is characterized in that, in mass fraction, comprises 10.0～20.0% imperatorin and 10.0～20.0% slow release medium, and all the other are adjuvant; Described slow release medium is one or more in the middle of hydroxypropyl emthylcellulose, polyvinylpyrrolidone, carbomer, methylcellulose, the ethyl cellulose.
2. imperatorin sustained release tablets as claimed in claim 1, it is characterized in that, comprise 12.0～16.7% imperatorin and 12.0～17.0% slow release medium, described slow release medium is two kinds in the middle of hydroxypropyl emthylcellulose, polyvinylpyrrolidone, carbomer, methylcellulose, the ethyl cellulose.
3. imperatorin sustained release tablets as claimed in claim 1, it is characterized in that, described adjuvant is made up of diluent, lubricant and binding agent, wherein, the mass fraction that diluent accounts for imperatorin sustained release tablets is 65.7～78.7%, the mass fraction that lubricant accounts for imperatorin sustained release tablets is 1.0～1.8%, and the mass fraction of binder constitutes imperatorin sustained release tablets is 0.3～1.0%.
4. imperatorin sustained release tablets as claimed in claim 3 is characterized in that, described diluent is one or both in the middle of lactose, starch, the dextrin.
5. imperatorin sustained release tablets as claimed in claim 3 is characterized in that, described lubricant is Pulvis Talci or magnesium stearate.
6. the preparation method of an imperatorin sustained release tablets is characterized in that, may further comprise the steps:
1) by percentage to the quality, imperatorin with 10.0～20.0%, 5.0～10.0% slow release medium and 65.7～78.7% mixing diluents are even, ratio according to imperatorin/binding agent=10g/2～10mL adds binding agent then, and fully wet granulation obtains wet granular behind the mixing;
2) wet granular being dried to moisture mass fraction under 50～60 ℃ is 1.0～3.0%, obtains dried granule;
3) dried granule is crossed 24 mesh sieve granulate after, with the slow release medium of dried granule and 5.0～10.0% and 1.0～1.8% the abundant mixing of lubricant, tabletting is made imperatorin sustained release tablets then again.
7. the preparation method of imperatorin sustained release tablets as claimed in claim 6 is characterized in that, described slow release medium is one or more in the middle of hydroxypropyl emthylcellulose, polyvinylpyrrolidone, carbomer, methylcellulose, the ethyl cellulose; Described diluent is one or both in the middle of lactose, starch, the dextrin; Described lubricant is Pulvis Talci or magnesium stearate.
8. the preparation method of imperatorin sustained release tablets as claimed in claim 6 is characterized in that, described binding agent is that volumetric concentration is that 60% ethanol, mass concentration are 0.5～3% CMC-Na aqueous solution or PVP-ethanol-water solution; Described PVP-ethanol-water solution is that PVP is dissolved in volumetric concentration is that the mass concentration of PVP is 5～15% in the gained solution in 75% the ethanol-water solution.
9. the preparation method of imperatorin sustained release tablets as claimed in claim 6 is characterized in that, the described slow release medium of step 1) is hydroxypropyl emthylcellulose, methylcellulose, ethyl cellulose; Step 2) described slow release medium is polyvinylpyrrolidone or carbomer.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103893169A (en) * | 2014-04-08 | 2014-07-02 | 崔新明 | Pharmaceutical composition for treating thyroid disease and application thereof |
| CN106619518A (en) * | 2017-02-07 | 2017-05-10 | 广东神农中医研究院(有限合伙) | Imperatorin flexible liposome as well as preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101032462A (en) * | 2006-12-20 | 2007-09-12 | 浙江大学 | Mexiletine Hydrochloride slow release reagent and preparing method thereof |
| CN101596171A (en) * | 2009-06-25 | 2009-12-09 | 昆明积大制药有限公司 | A kind of tamsulosin sustained release tablet and preparation method thereof |
-
2010
- 2010-07-14 CN CN2010102267146A patent/CN101897677B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101032462A (en) * | 2006-12-20 | 2007-09-12 | 浙江大学 | Mexiletine Hydrochloride slow release reagent and preparing method thereof |
| CN101596171A (en) * | 2009-06-25 | 2009-12-09 | 昆明积大制药有限公司 | A kind of tamsulosin sustained release tablet and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 《ANALYTICAL SCIENCES》 20090731 Sicen Wang et al Development and Validation of a Gas Chromatography-Mass Spectrom Method for the Determination of Imperatorin in Rat Plasma and tissue：application to study its pharmacokinetics 第25卷, 2 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103893169A (en) * | 2014-04-08 | 2014-07-02 | 崔新明 | Pharmaceutical composition for treating thyroid disease and application thereof |
| CN106619518A (en) * | 2017-02-07 | 2017-05-10 | 广东神农中医研究院(有限合伙) | Imperatorin flexible liposome as well as preparation method and application thereof |
| CN106619518B (en) * | 2017-02-07 | 2020-06-02 | 周乾 | Imperatorin flexible liposome and preparation method and application thereof |
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