CN102423492A - Chinese radish sulfane clathrate compound and preparation method thereof - Google Patents
Chinese radish sulfane clathrate compound and preparation method thereof Download PDFInfo
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- CN102423492A CN102423492A CN2011104610474A CN201110461047A CN102423492A CN 102423492 A CN102423492 A CN 102423492A CN 2011104610474 A CN2011104610474 A CN 2011104610474A CN 201110461047 A CN201110461047 A CN 201110461047A CN 102423492 A CN102423492 A CN 102423492A
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Abstract
The invention relates to a Chinese radish sulfane clathrate compound and a preparation method thereof. The invention solves the problem that the Chinese radish sulfane is not stable when being stored at room temperature, and can not be easily produced or applied to practice. The goal of the invention is implemented by forming a clathrate compound from Chinese radish sulfane and propenyl-beta-cyclodextrin. The implementation process comprises the following steps: reacting beta-cyclodextrin with bromopropylene under alkaline conditions, and processing to obtain propenyl-beta-cyclodextrin; and dissolving the propenyl-beta-cyclodextrin in distilled water, dropwisely adding corresponding chemical amount of Chinese radish sulfane ethanol solution into the propenyl-beta-cyclodextrin solution, and processing to obtain freeze-dried powder. After the Chinese radish sulfane propenyl-beta-cyclodextrin clathrate compound is stored at room temperature for half a year, the residue rate is up to 80%.
Description
Technical field
The present invention relates to clathrate of a kind of LSulforaphane and preparation method thereof.Be specifically related to utilize cyclodextrin derivative and LSulforaphane to form Subjective and Objective clathrate and preparation method thereof, belong to medical technical field.
Background technology
LSulforaphane (Sulforaphane) claim raphanin again, and molecular formula is C
6H
11NOS
2, being the isothiocyanate derivant, its structural formula is as follows:
LSulforaphane is a kind of cancer-resisting substance of strong effect, and more existence in brassicaceous vegetable is the highest with content in the Caulis et Folium Brassicae capitatae especially.Discover; LSulforaphane is the most significant isothiocyanic acid salt compounds such as antioxidation, anti-cancer, active anticancer, and contained LSulforaphane can effectively prevent the generation of cancers such as hepatocarcinoma, pulmonary carcinoma, carcinoma of prostate, breast carcinoma, rectal cancer, gastric cancer, adenocarcinoma, skin carcinoma in the Caulis et Folium Brassicae capitatae.
LSulforaphane can obtain through different chemical methodes is synthetic.1948; H.Schimd and P.Karrer (synthese der racemischen und der optisch aktiven formen des sulforaphans) obtain LSulforaphane through chemical method is synthetic the earliest, and it is a kind of spatial chemistry racemic mixture that this method obtains.After this, a lot of research worker have found that other various chemical methodes are used for synthetic LSulforaphane, but these methods all are easy to form the racemic mixture of LSulforaphane.It's a pity that LSulforaphane is a kind of unsettled Organic substance, because its unstability, LSulforaphane is difficult to production and selling.
Cyclodextrin (Cyclodextrin) is the general name of amylose a series of cyclic oligosaccharides of generation under cyclodextrin glycosyltransferase (CGTase) effect that is produced by bacillus cereus; What have actual application value is to contain 6; The molecule of 7 and 8 glucose units; Be called α respectively, β and γ cyclodextrin.Wherein α-CD and γ-CD dissolubility is big, is difficult to crystallization, and required cost is high, genotoxic potential is arranged, less application.And β-CD overcomes above-mentioned shortcoming, and after the chain rupture open loop forms oligosaccharide under the effect of the digestive enzyme of intestinal and enteric microorganism, can participate in the metabolism of body as a kind of carbohydrate, avoid accumulating in vivo, and be a kind of ideal safety non-toxic carrier.
In aqueous solution, thereby the hydrophobic part of drug molecular structure can form clathrate through the hydrone of cyclodextrin instead inner chamber, in case drug molecule gets into the cyclodextrin inner chamber, medicine just can dissolve and form aqueous solution.The more important thing is in the drug-cyclodextrin clathrate forming process, do not have the formation and the fracture of covalent bond between drug molecule and the cyclodextrin, clathrate can form dynamic equilibrium between drug molecule and the cyclodextrin molecular freely.
The water solublity of beta-schardinger dextrin-is relatively poor, and this is easy to cause drug-cyclodextrin clathrate deposition.The reason that beta-schardinger dextrin-dissolubility in water is low is owing on lattice, form intramolecular hydrogen bond between C2 and the C3 hydroxyl, so any one can replace the group of C2 and C3 hydroxyl, even hydrophobic methoxy group, can both increase the water solublity of beta-schardinger dextrin-.In addition, these substitution reactions often produce a large amount of isomerss, thereby the cyclodextrin of crystal form is transformed into amorphous mixture, and this has also increased the water solublity of beta-cyclodextrin derivative.The derivant of cyclodextrin mainly is divided into the sulfoalkyl etherification derivative, methylates or alkyl derivative, hydroxyalkylation derivant etc. at present.
People (US 2008/0176942 A1) such as Ido D. D. utilize cyclodextrin and LSulforaphane to form clathrate, can improve the stability of LSulforaphane to a certain extent, reach 90% at month residual rate of room temperature preservation.But the room temperature preservation problem does not still solve for a long time, and cyclodextrin-LSulforaphane clathrate room temperature preservation is after half a year, and the LSulforaphane more than 50% decomposes owing to unstable, and this is unfavorable for production and selling very much.
Summary of the invention
Acrylic-the Benexate Hydrochloride that the purpose of this invention is to provide a kind of LSulforaphane has overcome the instability problem of LSulforaphane under long room temperature preservation.LSulforaphane room temperature preservation residual rate half a year reaches more than 80%, enables to realize production and selling.
Another object of the present invention provides the method for preparing of the acrylic-Benexate Hydrochloride of above-mentioned LSulforaphane.
A purpose more of the present invention provides the pharmaceutical composition of the acrylic-Benexate Hydrochloride that comprises such LSulforaphane.
Of the present inventionly advance the clathrate that a purpose provides a kind of LSulforaphane, the application in the preparation cancer therapy drug.
The object of the invention is achieved through the method that propylene group-beta-cyclodextrin and LSulforaphane form clathrate.Acrylic-the Benexate Hydrochloride of LSulforaphane is made up of following raw material in molar ratio: LSulforaphane and propylene group-beta-cyclodextrin mol ratio are 1:0.2～4; The optimum molar proportioning is 1:0.6～1.5.Find that through test enclose is satisfactory for result with mol ratio 1:0.6～1.5 ratio clathrate productive rates height.
The technology and the method for this raising LSulforaphane stability may further comprise the steps and process conditions:
1, the propylene group-beta-cyclodextrin is synthetic
(1) at room temperature, NaOH and distilled water are joined in the there-necked flask, be warming up to 40～60 ° of C after the stirring and dissolving, add beta-schardinger dextrin-, stirring is dissolved it fully;
(2) will go up the solution that obtains of step and reduce to room temperature, dripping bromine propylene under agitation, after dropwising, room temperature reaction 4h is to the bromopropene complete reaction;
(3) after reaction finishes, reactant liquor is neutralized to neutrality, filters with hydrochloric acid, washing with alcohol, acetone extract, the dialysis desalting postlyophilization makes white powder propylene group-beta-cyclodextrin.
2, the acrylic of LSulforaphane-Benexate Hydrochloride preparation
According to LSulforaphane and propylene group-beta-cyclodextrin mol ratio is the ratio of 1:0.2～4, will be dissolved in the LSulforaphane of organic solvent, slowly is added drop-wise in the aqueous solution that contains the propylene group-beta-cyclodextrin, ultrasonic, stirs, and gets inclusion complex in solution; Filter,, get the clathrate powder through lyophilization.
The used organic solvent of above-mentioned method for preparing is selected from methanol, ethanol, isopropyl alcohol or acetone.
Above-mentioned method for preparing can more specifically realize by following operational approach:
Accurately a certain amount of propylene group-beta-cyclodextrin of weighing is dissolved in the distilled water, and stirring and dissolving obtains saturated solution.Be dissolved in the ethanol according to mol ratio 1:0.2～a certain amount of LSulforaphane of 4 weighings, slowly be added drop-wise in the propylene group-beta-cyclodextrin aqueous solution and form suspension, ultrasonic 20～30min continues high-speed stirred 10～24h under the room temperature.Use the 0.45mm filtering with microporous membrane, filtrate through fill lyophilization.Get white powder, be the acrylic-Benexate Hydrochloride of LSulforaphane.
The invention has the advantages that acrylic-Benexate Hydrochloride that a kind of LSulforaphane soluble in water is provided; Greatly increased the stability of LSulforaphane; Residual rate is still up to 80% after half a year to make the LSulforaphane room temperature preservation, and enabling production and selling becomes possibility.
The present invention verifies that the stability-enhanced method of LSulforaphane is HPLC (HPLC): after LSulforaphane is preserved a period of time; Residual LSulforaphane detects through HPLC, and chromatogram flow phase can be separated LSulforaphane and dissolves from the propylene group-beta-cyclodextrin.Make standard curve with freeze dried LSulforaphane powder standard substance when testing for the first time.
The sample preservation condition: the acrylic-Benexate Hydrochloride of LSulforaphane is preserved under two kinds of conditions: room temperature and 40 ° of C high temperature.Through the residual rate of HPLC analysis LSulforaphane, analysis result is seen accompanying drawing 1 and Fig. 2 to sample after preserving the different time section.
The sample solution preparation: accurately take by weighing 20～50mg sample and be dissolved among the DMF, then further dilute with the 1mL deionized water, ultrasonic about 10min filters with the 0.45mm microfilter.It is the same that the LSulforaphane standard solution of variable concentrations prepares process.Sample detects through HPLC.
Chromatographic condition: chromatographic column is anti-phase C18 post (250mm ' 4.6mm, 5mm, Diamodsil
TM), the ultraviolet detection signal is 254nm, and mobile phase is that 20% acetonitrile solution gradient is increased to 60% acetonitrile solution (surpassing 10min), and flow velocity is 1.0ml/min, and sample size is 10mL.
The result shows; The acrylic of LSulforaphane-Benexate Hydrochloride room temperature preservation is after half a year; Residual LSulforaphane is still up to 80%; Even preserve half a year at 40 ° of C high temperature, residual LSulforaphane is still near 50%, and this confirms that acrylic-Benexate Hydrochloride can effectively improve the stability of LSulforaphane.
The present invention also comprises a kind of pharmaceutical composition, and the clathrate that comprises with LSulforaphane is effective ingredient and pharmaceutically suitable carrier.
The clathrate of LSulforaphane provided by the present invention is applied in the preparation cancer therapy drug.
Description of drawings
Fig. 1 is the residual rate of LSulforaphane room temperature preservation different time.
Fig. 2 is the residual rate that 40 ° of C high temperature of LSulforaphane are preserved different time.
The specific embodiment
Below in conjunction with embodiment the present invention is done further explanation:
Embodiment 1
Distinguish weighing sodium hydroxide (NaOH) 12g and measure the 250mL deionized water and join in three mouthfuls of round-bottomed flasks of 500ml stirring and dissolving.Behind warming-in-water to the 60 ° C, take by weighing beta-schardinger dextrin-120g and join in the flask, stirring is dissolved it fully.Reduce to room temperature, in stirring, slowly drip the 80g bromopropene in flask, after dropwising; Room temperature reaction 4h, reaction is neutralized to neutrality with the 1mol/L hydrochloric acid solution with reactant liquor after finishing; Filter washing with alcohol, acetone extract; The dialysis desalting postlyophilization makes propylene group-beta-cyclodextrin 98.2g, and yield 81.8%, substitution value are 5.4.
Embodiment 2
Distinguish weighing sodium hydroxide (NaOH) 12g and measure the 250mL deionized water and join in three mouthfuls of round-bottomed flasks of 500ml stirring and dissolving.Behind warming-in-water to the 60 ° C, take by weighing beta-schardinger dextrin-120g and join in the flask, stirring is dissolved it fully.Reduce to room temperature, in stirring, slowly drip the 100g bromopropene in flask, after dropwising; Room temperature reaction 4h, reaction is neutralized to neutrality with the 1mol/L hydrochloric acid solution with reactant liquor after finishing; Filter washing with alcohol, acetone extract; The dialysis desalting postlyophilization makes propylene group-beta-cyclodextrin 103.8g, and yield 86.5%, substitution value are 6.8.
Embodiment 3
The propylene group-beta-cyclodextrin that weighing 2.6g embodiment 1 obtains is dissolved in the 250mL water for injection, and stirring and dissolving obtains saturated solution.Take by weighing LSulforaphane 1.8g, be dissolved in the 4mL dehydrated alcohol.Under agitation, the LSulforaphane ethanol solution slowly is added drop-wise in the propylene group-beta-cyclodextrin aqueous solution forms suspension, ultrasonic 20～30min continues high-speed stirred 24h under the room temperature.Use the 0.45mm filtering with microporous membrane, filtrate through fill lyophilization.Make the acrylic-Benexate Hydrochloride white powder (raw material LSulforaphane and propylene group-beta-cyclodextrin mol ratio are about 1:0.2) of LSulforaphane, HPLC detects and to obtain that LSulforaphane is 0.42g in the clathrate, and inclusion rate is 23%.
Embodiment 4
The propylene group-beta-cyclodextrin that weighing 13g embodiment 1 obtains is dissolved in the 250mL water for injection, and stirring and dissolving obtains saturated solution.Take by weighing LSulforaphane 1.8g, be dissolved in the 4mL dehydrated alcohol.Under agitation, the LSulforaphane ethanol solution slowly is added drop-wise in the propylene group-beta-cyclodextrin aqueous solution forms suspension, ultrasonic 20～30min continues high-speed stirred 24h under the room temperature.Use the 0.45mm filtering with microporous membrane, filtrate through fill lyophilization.Make the acrylic-Benexate Hydrochloride white powder (raw material LSulforaphane and propylene group-beta-cyclodextrin mol ratio are about 1:1) of LSulforaphane, HPLC detects and to obtain that LSulforaphane is 1.35g in the clathrate, and inclusion rate is 75%.
Embodiment 5
The propylene group-beta-cyclodextrin that weighing 26g embodiment 1 obtains is dissolved in the 250mL water for injection, and stirring and dissolving obtains saturated solution.Take by weighing LSulforaphane 1.8g, be dissolved in the 4mL dehydrated alcohol.Under agitation, the LSulforaphane ethanol solution slowly is added drop-wise in the propylene group-beta-cyclodextrin aqueous solution forms suspension, ultrasonic 20～30min continues high-speed stirred 24h under the room temperature.Use the 0.45mm filtering with microporous membrane, filtrate through fill lyophilization.Make the acrylic-Benexate Hydrochloride white powder (raw material LSulforaphane and propylene group-beta-cyclodextrin mol ratio are about 1:2) of LSulforaphane, HPLC detects and to obtain that LSulforaphane is 0.72g in the clathrate, and inclusion rate is 40%.
Embodiment 6
The propylene group-beta-cyclodextrin that weighing 52g embodiment 1 obtains is dissolved in the 250mL water for injection, and stirring and dissolving obtains saturated solution.Take by weighing LSulforaphane 1.8g, be dissolved in the 4mL dehydrated alcohol.Under agitation, the LSulforaphane ethanol solution slowly is added drop-wise in the propylene group-beta-cyclodextrin aqueous solution forms suspension, ultrasonic 20～30min continues high-speed stirred 24h under the room temperature.Use the 0.45mm filtering with microporous membrane, filtrate through fill lyophilization.Make the acrylic-Benexate Hydrochloride white powder (raw material LSulforaphane and propylene group-beta-cyclodextrin mol ratio are about 1:4) of LSulforaphane, HPLC detects and to obtain that LSulforaphane is 0.51g in the clathrate, and inclusion rate is 28%.
Embodiment 7
The propylene group-beta-cyclodextrin that weighing 2.6g embodiment 2 obtains is dissolved in the 250mL water for injection, and stirring and dissolving obtains saturated solution.Take by weighing LSulforaphane 1.8g, be dissolved in the 4mL dehydrated alcohol.Under agitation, the LSulforaphane ethanol solution slowly is added drop-wise in the propylene group-beta-cyclodextrin aqueous solution forms suspension, ultrasonic 20～30min continues high-speed stirred 24h under the room temperature.Use the 0.45mm filtering with microporous membrane, filtrate through fill lyophilization.Make the acrylic-Benexate Hydrochloride white powder (raw material LSulforaphane and propylene group-beta-cyclodextrin mol ratio are about 1:0.2) of LSulforaphane, HPLC detects and to obtain that LSulforaphane is 0.67g in the clathrate, and inclusion rate is 37%.
Embodiment 8
The propylene group-beta-cyclodextrin that weighing 13g embodiment 2 obtains is dissolved in the 250mL water for injection, and stirring and dissolving obtains saturated solution.Take by weighing LSulforaphane 1.8g, be dissolved in the 4mL dehydrated alcohol.Under agitation, the LSulforaphane ethanol solution slowly is added drop-wise in the propylene group-beta-cyclodextrin aqueous solution forms suspension, ultrasonic 20～30min continues high-speed stirred 24h under the room temperature.Use the 0.45mm filtering with microporous membrane, filtrate through fill lyophilization.Make the acrylic-Benexate Hydrochloride white powder (raw material LSulforaphane and propylene group-beta-cyclodextrin mol ratio are about 1:1) of LSulforaphane, HPLC detects and to obtain that LSulforaphane is 1.45g in the clathrate, and inclusion rate is 81%.
Embodiment 9
The propylene group-beta-cyclodextrin that weighing 26g embodiment 2 obtains is dissolved in the 250mL water for injection, and stirring and dissolving obtains saturated solution.Take by weighing LSulforaphane 1.8g, be dissolved in the 4mL dehydrated alcohol.Under agitation, the LSulforaphane ethanol solution slowly is added drop-wise in the propylene group-beta-cyclodextrin aqueous solution forms suspension, ultrasonic 20～30min continues high-speed stirred 24h under the room temperature.Use the 0.45mm filtering with microporous membrane, filtrate through fill lyophilization.Make the acrylic-Benexate Hydrochloride white powder (raw material LSulforaphane and propylene group-beta-cyclodextrin mol ratio are about 1:2) of LSulforaphane, HPLC detects and to obtain that LSulforaphane is 0.81g in the clathrate, and inclusion rate is 45%.
The propylene group-beta-cyclodextrin that weighing 52g embodiment 2 obtains is dissolved in the 250mL water for injection, and stirring and dissolving obtains saturated solution.Take by weighing LSulforaphane 1.8g, be dissolved in the 4mL dehydrated alcohol.Under agitation, the LSulforaphane ethanol solution slowly is added drop-wise in the propylene group-beta-cyclodextrin aqueous solution forms suspension, ultrasonic 20～30min continues high-speed stirred 24h under the room temperature.Use the 0.45mm filtering with microporous membrane, filtrate through fill lyophilization.Make the acrylic-Benexate Hydrochloride white powder (raw material LSulforaphane and propylene group-beta-cyclodextrin mol ratio are about 1:4) of LSulforaphane, HPLC detects and to obtain that LSulforaphane is 0.56g in the clathrate, and inclusion rate is 31%.
Embodiment 11
Acrylic-the Benexate Hydrochloride of the LSulforaphane that makes in embodiment 3,4,5,6,7,8,9 and 10 is placed on respectively in room temperature environment and the 40 ° of C hot environments; Preserve half a year; LSulforaphane content in the test pack compound when the 7th day, 14 days, 1 month, 2 months, three months and 6 months respectively, test result is seen accompanying drawing 1 and Fig. 2.
Claims (8)
1. the clathrate of a LSulforaphane is characterized in that, said clathrate is made up of following raw material in molar ratio, and the mol ratio of LSulforaphane and propylene group-beta-cyclodextrin is 1:0.2～4.
2. according to the clathrate of the described a kind of LSulforaphane of claim 1, it is characterized in that the mol ratio of described LSulforaphane and propylene group-beta-cyclodextrin is 1:0.6～1.5.
3. according to the clathrate of claim 1 or 2 described a kind of LSulforaphane, it is characterized in that the substitution value of described propylene group-beta-cyclodextrin is 5～8.
4. according to the method for preparing of the clathrate of the described a kind of LSulforaphane of claim 3, it is characterized in that the method for preparing of described propylene group-beta-cyclodextrin comprises the steps:
(1) at room temperature, NaOH and distilled water are joined in the there-necked flask, be warming up to 40～60 ° of C after the stirring and dissolving, add beta-schardinger dextrin-, stirring is dissolved it fully;
(2) will go up the solution that obtains of step and reduce to room temperature, dripping bromine propylene under agitation, after dropwising, room temperature reaction 4h is to the bromopropene complete reaction;
(3) after reaction finishes, reactant liquor is neutralized to neutrality, filters with hydrochloric acid, washing with alcohol, acetone extract, the dialysis desalting postlyophilization makes white powder propylene group-beta-cyclodextrin.
5. according to the method for preparing of the clathrate of claim 1 or 2 described a kind of LSulforaphane, it is characterized in that, in the ratio in claim 1 or 2; To be dissolved in the LSulforaphane of organic solvent, slowly be added drop-wise in the aqueous solution that contains the propylene group-beta-cyclodextrin, ultrasonic; Stir, get inclusion complex in solution; Filter,, get the clathrate powder through lyophilization.
6. press the method for preparing of the clathrate of the described a kind of LSulforaphane of claim 5, it is characterized in that said organic solvent is methanol, ethanol, isopropyl alcohol or acetone.
7. pharmaceutical composition, the clathrate that comprises a kind of LSulforaphane of claim 1 or 2 is effective ingredient and must uses carrier.
8. according to the clathrate of claim 1 or 2 described a kind of LSulforaphane, the application in the preparation cancer therapy drug.
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Cited By (5)
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| WO2013179057A1 (en) * | 2012-06-01 | 2013-12-05 | Pharmagra Labs, Inc. | Method of synthesising sulforaphane |
| WO2013179056A1 (en) * | 2012-06-01 | 2013-12-05 | Pharmagra Labs, Inc. | Sulforaphane isolation and purification |
| CN103877066A (en) * | 2014-02-21 | 2014-06-25 | 中国人民解放军第二军医大学 | Method for preparing docetaxel and sulforaphane loaded self-assembled nano-particle and application of nano-particle |
| CN104284885A (en) * | 2012-03-09 | 2015-01-14 | 高等科学研究委员会 | Sulforaphane-derived compounds, production method thereof and the medical, food and cosmetic use of same |
| CN110403909A (en) * | 2019-08-21 | 2019-11-05 | 青岛农业大学 | A kind of raphanin pulvis and preparation method thereof |
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Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104284885A (en) * | 2012-03-09 | 2015-01-14 | 高等科学研究委员会 | Sulforaphane-derived compounds, production method thereof and the medical, food and cosmetic use of same |
| CN104284885B (en) * | 2012-03-09 | 2018-03-27 | 高等科学研究委员会 | Compound, its preparation method and its medical treatment, foods and cosmetics purposes derived from sulforaphane |
| US9603828B2 (en) | 2012-06-01 | 2017-03-28 | Pharmagra Labs, Inc. | Sulforaphane isolation and purification |
| US10864186B2 (en) | 2012-06-01 | 2020-12-15 | Pharmagra Labs, Inc. | Method of synthesising sulforaphane |
| CN104640573A (en) * | 2012-06-01 | 2015-05-20 | 法玛格拉实验室公司 | Sulforaphane isolation and purification |
| JP2015519358A (en) * | 2012-06-01 | 2015-07-09 | ファームアグラ・ラブズ，インコーポレイテッド | Isolation and purification of sulforaphane |
| US11571406B2 (en) | 2012-06-01 | 2023-02-07 | Pharmagra Labs, Inc. | Method of synthesising sulforaphane |
| US9567405B2 (en) | 2012-06-01 | 2017-02-14 | Pharmagra Labs, Inc. | Method of synthesising sulforaphane |
| WO2013179057A1 (en) * | 2012-06-01 | 2013-12-05 | Pharmagra Labs, Inc. | Method of synthesising sulforaphane |
| JP2017200931A (en) * | 2012-06-01 | 2017-11-09 | ファームアグラ・ラブズ，インコーポレイテッド | Sulforaphane isolation and purification |
| WO2013179056A1 (en) * | 2012-06-01 | 2013-12-05 | Pharmagra Labs, Inc. | Sulforaphane isolation and purification |
| US10307390B2 (en) | 2012-06-01 | 2019-06-04 | Pharmagra Labs, Inc. | Method of synthesising sulforaphane |
| CN103877066B (en) * | 2014-02-21 | 2016-08-24 | 中国人民解放军第二军医大学 | Carry preparation method and the application of the self-assembled nanometer grain of docetaxel and sulforaphane |
| CN103877066A (en) * | 2014-02-21 | 2014-06-25 | 中国人民解放军第二军医大学 | Method for preparing docetaxel and sulforaphane loaded self-assembled nano-particle and application of nano-particle |
| CN110403909A (en) * | 2019-08-21 | 2019-11-05 | 青岛农业大学 | A kind of raphanin pulvis and preparation method thereof |
| CN110403909B (en) * | 2019-08-21 | 2021-08-31 | 青岛农业大学 | Sulforaphene powder and preparation method thereof |
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Application publication date: 20120425 |