CN102552338A - Paclitaxel oral anticancer preparation obtained by nontoxic extraction from complete stool of Chinese yew and preparation method thereof - Google Patents
Paclitaxel oral anticancer preparation obtained by nontoxic extraction from complete stool of Chinese yew and preparation method thereof Download PDFInfo
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- CN102552338A CN102552338A CN2012100303289A CN201210030328A CN102552338A CN 102552338 A CN102552338 A CN 102552338A CN 2012100303289 A CN2012100303289 A CN 2012100303289A CN 201210030328 A CN201210030328 A CN 201210030328A CN 102552338 A CN102552338 A CN 102552338A
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Abstract
The invention provides a paclitaxel oral anticancer preparation obtained by nontoxic extraction from a complete stool of Chinese yew and preparation method thereof, which uses Chinese yew in Northeast China as the main raw material, by a ethanol immersion 16-step method and a nontoxic extraction technology, to obtain a 30% paclitaxel crude product, which is used as main raw material of paclitaxel drug wine and paclitaxel oral liquid. Based on drug effect research, the prepared oral anticancer preparation has greatly visble treatment effect on late period caser patients of 20 kinds of different singularity and the late period and anaphase cancer patients which is failure on combined chemotherapy, and the preparation has advantages of good ease pain effect and non-poison.
Description
Technical field
The present invention relates in the technical field of Chinese medicines, utilizes tame Ramulus et folium taxi cuspidatae Herb to carry out the method for preparing of soak with ethanol, nontoxic extraction paclitaxel and oral anticancer preparation thereof.
Background technology
Ramulus et folium taxi cuspidatae is extracted the production technology of paclitaxel, according at present relevant both at home and abroad report and pertinent literature in introduce use CO arranged
2Diversified extraction process modes such as extraction and ultrasonic extraction.The CO2 extraction though ultrasonic extraction technology is advanced, must be got the rate height; But paclitaxel and the residual equivalent that still has after some chemical solvent is handled exist; Raw material after the extraction though the patient can tolerate its toxicity, must cause the secondary injury to the patient again as ejection preparation; If the cancer to late-anaphase or combined chemotherapy failure is suffered from, will quicken its dead speed.Research experiment shows that the paclitaxel of nontoxic extraction is better than deleterious paclitaxel, and physiologically active is still stronger; Because of nontoxic extraction has kept many tumor-suppression activity materials; Especially at this moment the retaining of micromolecular compound in the bean China fir pigment alleviate cancer pain, and the anticancer growth is very important.
The present invention adopts follow-on 16 footwork ultrafilter membrane separation and Extraction methods to extract the bullion paclitaxel, does not use chemical solvent, no chemical residual, and its safety, the rate of must getting are all very high.The nontoxic extraction process of this 16 footworks is also rare at home at present.
Summary of the invention
Order of the present invention ground is to medicine enterprise the nontoxic extraction paclitaxel of Ramulus et folium taxi cuspidatae Herb bullion raw material to be provided, and for manufacturing and guaranteeing oral anticancer preparation paclitaxel medicated wine, the safety of paclitaxel oral liquid provides the technology path of science to support.
Raw material extracts the method for preparing with oral formulations:
1, the nontoxic extraction process of paclitaxel raw material:
Roguing, O
3Water cleaning → section → oven dry → pulverizing → nanometer ultra micro breaking cellular wall → soak with ethanol peels off → and just filter → detoxification treatment → low pressure macropore ultrafiltration → high pressure aperture ultrafiltration → chromatography → vacuum infiltration concentrates → reclaims ethanol → secondary detoxification → vacuum lyophilization → crystalline solid pulverizing.
2, processing step explanation:
(1) roguing, cleaning: earth and other contaminant removals of Ramulus et folium taxi cuspidatae Herb dry product surface attachment are fallen, put into O again
3Clean in the water service sink, through O
3The Oxidation of water, the residue removal of pathogenic bacteria, syphilis and fertilizer and pesticide that can be effectively that the Ramulus et folium taxi cuspidatae Herb is surperficial falls;
(2) after the Ramulus et folium taxi cuspidatae Herb after will cleaning drains away the water, thinly slice;
(3) dry: the Ramulus et folium taxi cuspidatae thin slice is sent in the hot air circular drying machine dried 3 hours;
(4) the Ramulus et folium taxi cuspidatae fragment after the oven dry is being pulverized through rustless steel pulverizing machine;
(5) ultra micro breaking cellular wall: the order ground of nanometer ultra micro breaking cellular wall is because paclitaxel alkane diterpene generic micromolecular compound, tightly be posted in the karyon with karyon outside; Add the cell colloid and cohere the strong adhesion cause; Promptly be swelling cracking after the soak with ethanol, but still have part alkane diterpene-kind compound also can't dissociate out, adopt ultra micro nanoscale wall-breaking machine to pulverize 300 orders; Even littler microgranule, can effectively obtain diterpene and other chemical compound;
(6) soak with ethanol is peeled off: because paclitaxel alkane Diterpenes is water insoluble; Be soluble in alcoholic acid characteristic; Adopt 95% medical ethanol and Ramulus et folium taxi cuspidatae to soak in proportion, indirect was soaked after 24 hours, and liquid temperature indirect to diterpene-kind compound physiologically active is still being located in stable boundary's degree; Stirred 20 minutes fast, impel the stream of alkane diterpene-kind compound under preference temperature to peel off out in impacting mutually;
(7) just filter: the solution after stirring is peeled off filters with the filter screen of 500 order fineness, and filtering residue carries out the secondary soak with ethanol again;
(8) detoxification treatment: the liquid temperature raises gradually during solution indirect to preference temperature after will just filtering; Deleterious lightweight volatile oil floats to the alcoholic solution surface on can be progressively; And following temperature rising is high and build up to the center; At this moment adsorb with oil-Absorbing Sheets, also available rustless steel soup ladle takes out, centralized and unified in the future extraction volatile oil;
(9) low pressure macropore ultrafiltration: adopt the ultrafilter membrane seperator, the setting granularity is 0.01um, and the granularity of paclitaxel alkane diterpene-kind compound is 0.01-0.002um.So, at first the alcoholic solution pressurization of detoxification to be held back through low pressure macropore 0.01um ultrafiltration, trapped substance is a crude fibre, the macromolecular substances of no values such as micronic dust, colloid;
(10) high pressure aperture ultrafiltration: low pressure macropore permeate again through the holding back of high pressure aperture 0.001um, is promptly obtained the sized molecules concentrated solution of paclitaxel alkane Diterpenes and other chemical compound;
(11) chromatography: with high pressure aperture ultrafiltration permeate, the sized molecules concentrated solution of holding back through the eluent and the ultrafiltration of high pressure aperture of silica gel column chromatography vacuum state infiltration absorption merges;
(12) vacuum infiltration concentrates: the concentrated solution that merges is carried out warm vacuum infiltration concentrates in 3 hours, promptly obtain the paste body shape after sized molecules merges.
(13) reclaim ethanol: the micromolecule ethanol liquid that micromolecule ethanol liquid and the chromatography of vacuum infiltration seen through merges, with distillator distillation recovery reuse;
(14) secondary detoxification: the spissated paste of vacuum infiltration is poured in the stainless steel disc of a thin-walled; Sent in the thermostatic drying chamber airtight suction empty dry 6 hours; Because also have part lightweight bean China fir quintessence oil and ethanol in the spissated mastic, when treating that the cream temperature rises gradually, bean China fir quintessence oil can together distil with ethanol and evaporate; After 6 hours, can present no alcoholic acid crystalline solid;
(15) low-temperature vacuum drying: the no alcohol crystal body of substantially dry is smashed; Put into another thin-walled stainless steel disc, send in the vacuum freeze drier, under the above vacuum state of low temperature 38 degree; Lyophilization 24 hours promptly becomes the paclitaxel crystalline solid of nontoxic extraction;
(16) crystalline solid is pulverized: it is 80 orders that dried crystalline solid is pulverized through the rustless steel high speed disintegrator fast, can get the paclitaxel bullion, and color is the irregular crystalline powder of light red, is 30% through measuring content of taxol.
The present invention utilizes its ultrafiltration extraction, inspissation, has improved the product yield greatly.The ultrafilter membrane of different molecular weight cutoff also capable of using is realized the further grading purification of paclitaxel, also can paclitaxel be divided into several single relatively molecular weight grades, the elaboration paclitaxel of preparation homogeneous.Secondary detoxification treatment ultrafiltration is carried out detoxification and processed before processing after makes paclitaxel toxicity reduce more than 98%, and effective active does not destroy; And it is simple to operate; Only need control operation pressure, flow velocity and filter liquor concentration get final product, and this is big and distribution broad for molecular weight; Big and the unsettled again paclitaxel alkane Diterpenes of solution viscosity is undoubtedly a kind of extraction separation means that have development potentiality.
3, the physical state of bullion paclitaxel and physicochemical property:
Contain chemical compounds such as protein, aminoacid, mineral, biotin and paclitaxel alkane Diterpenes, taxine, taxusin, Ramulus et folium taxi cuspidatae polysaccharide, Ramulus et folium taxi cuspidatae red pigment, Ramulus et folium taxi cuspidatae tannin, Ramulus et folium taxi cuspidatae polyphenol, Ramulus et folium taxi cuspidatae adenosine class in the bullion paclitaxel; The stickiness of its bullion is bigger; Color is the light red crystalline powder; Mildly bitter flavor, little puckery, a strand loose China fir fragrance flavor is arranged.The paclitaxel bullion is prone to moisture absorption, and stickiness increased when general room temperature 15 degree were above, progressively formed thick fluid; Temperature drops to 5 degree when following; Be reduced into ingot, constant through detecting its physiologically active, but microorganism increases; Adopt sub-zero deepfreeze or when freezing, its physical state and physical and chemical index are comparatively stable.
4, toxicological test
(1) anxious malicious LD50 test: divides three experimental grouies, the elaboration paclitaxel of injection 99% content that the 1st group of test raw material looked forward to providing by the Shanghai medicine, color is white irregular crystalline powder, after releasing with PEG400 alkene, is deployed into the crude drug of 100mg/ml; The 2nd group of self-control ethanol extraction paclitaxel bullion that test raw material is extracted by Ramulus et folium taxi cuspidatae base, Heilongjiang Province, content is 1%.Color is the maroon crystalline particle, after releasing with PEG400 alkene, is deployed into the crude drug of 2g; The 3rd group of test raw material belongs to the paclitaxel bullion of the nontoxic extraction of the present invention, and content is 30%, and color is the light red crystalline powder, after releasing with PEG400 alkene, is deployed into the crude drug of 2g/ml.Test 1 group, 2 groups, 3 groups the Mus of being tried and adopt Shanghai ICR kind mice, every group each 10, male and female half and half; After all stopping eating 10 hours, administration is fed in disposable filling, observes 3 days; The 1st receives examination group in 5 hours successively dead 2 after the administration, in 9 hours dead again 1, remains the survival of slowly recovering of 7 Mus; After the administration the 2nd receives examination group in 5 hours dead 1, and other 9 occur unusually, but return to normal after 6 hours, and it is unusual that the 3rd after the administration occurred by none Mus of examination group, and none is only dead.Test result shows the 1st group, utilizes the elaboration paclitaxel of GB extraction process, is tried dead 3 of Mus, and toxicity is bigger; The 2nd group is the bullion paclitaxel in Ramulus et folium taxi cuspidatae base, Heilongjiang Province, is tried dead 1 of Mus, has certain toxicity; The 3rd group is the paclitaxel bullion of the nontoxic extraction of the present invention, and none is only dead to be tried Mus.
(2) maximum tolerated dose test
With 40/kg of ICR kind mice, male and female half and half, administration 2g/ml is fed in disposable filling after stopping eating 10 hours; Administration is 2 times in the paclitaxel of nontoxic extraction, content 30%, one day; Accumulated dose is the 160g/kg crude drug, and this dosage is equivalent to the adult and calculates by the 60kg body weight, is 1200 times of oral dose 0.034g.Only have 2 slight abnormality to occur in 3 hours after the mice administration, return to normal after 4 hours, none is only dead in 3 days.Through conventional breeding observing 20 days, body weight slightly was lighter than corresponding time matched group P＜0.03 in mildly subnormal 2 mices the 9th day after administration occurring, and all the other are no abnormal.Therefore, the maximum tolerated dose of mice is 1200 times of the clinical plan oral dose of adult, and test result shows that toxicity is very little.
5, anticancer test
(1) with the paclitaxel bullion of the nontoxic extraction of the present invention; Alkene is released the crude drug that proportioning becomes 2g/ml, and content of taxol is 30%, injects and cultivates in 46 years old active female mammary gland JEG-3 incubator; Constant temperature culture is the microexamination discovery after 10 hours, most of repressed not the moving at all of breast carcinoma cell strain.
(2) with breast cancer cell 32 strains with distilled water miscible after, the outer Intradermal injection of the female Mus breast of giving 10 3 ages respectively makes its infection, every Mus is injected about 0.3ml respectively, but breast carcinoma cell strain quantity is not quite clear among the 0.3ml.Observe discovery in 3 days, 10 Mus all occur unusually, confirm all to infect, and have 8 molluscum contagiosum gland protuberances outstanding when treating the 9th day, and movable number of times and food-intake reduce relatively, and distinctly shriek appears in Mus sometimes.Irritate stomach 2 every day in the time of the 10th day, daily dose 3.4mg paclitaxel, and successive administration 2 months is during after the administration the 6th day; Appetite, movable number of times increases to some extent, and shriek disappears basically; Basically recovered in the 30th day, lump diminishes, this disappearance of most of ethyl; After 2 months, the mastadenoma piece of protuberance except that have 1 slightly diminish, all the other 7 all disappear.Experiment showed, that nontoxic paclitaxel bullion has very notable therapeutic effect to breast carcinoma, and analgesic activity is better, performance without any side effects.
(3) suffer from skin carcinoma, pulmonary carcinoma, lymphatic cancer, hepatocarcinoma (all among chemicotherapy) patient and take the paclitaxel oral liquid voluntarily through several, take every day 2 times, each 10ml/ props up, and includes paclitaxel bullion 1g/ and props up, and serve on 3 months, and auxiliary cancer resistant effect is obvious especially.Especially liver cancer patient, 51 years old, the male, initial survey tumor piece 0.98-1.36, AFP is 6902, takes oral liquid 1 month, AFP reduces to and reduced to 80 in 1150,2 months, takes 3 months residual focuses of the color ultra moulding of check and does not have movable sign.Experiment shows that the oral anticancer preparation effect of the paclitaxel of nontoxic extraction is extremely remarkable, and analgesic activity is relatively good.
(4) take the paclitaxel oral liquid voluntarily through tens subhealth state men and women after, feel full of physical strength, energy improves; Vigor is arranged; Sleep, easy catching a cold not, this and nontoxic paclitaxel have the haemolysis thromboembolism preventing; Antiviral, antiinflammatory, anticancer relevant with the enhancing immunity effect, this just provides certain theory property foundation for developing paclitaxel medicinal raw material and oral formulations.
6, the method for preparing of the oral anticancer preparation of paclitaxel
(1) paclitaxel medicated wine: the Herba bromi japonici wine 50kg with 38 degree, put into a high capacity rustless steel container, indirect 40 degree are being put into 5kg paclitaxel bullion; Fully stirred 20 minutes, treat that it is all after the dissolving, with the membrane filtration of 0.1um, metering filling; Every bottle of 250ml, paclitaxel medicated wine is used to treat usefulness, day clothes 2 times, each 10ml; Include paclitaxel bullion 1g, prevention usefulness, every day 1 time, each 10ml.
Be dissolved in ethanol owing to paclitaxel is water insoluble, so in fine wine, add the paclitaxel dissolving soon, do not precipitate, the color pinkiness of wine does not have float, and is translucent, and mouthfeel is good, free from extraneous odour, and medical substance is active strong.
The wine difference of Herba bromi japonici wine and other grain brew is: contain rich in protein, mineral, fat, carbohydrate in the Herba bromi japonici, main is to contain the linoleic acid very useful to human body, to the middle-aged and elderly people blood fat reducing; Blood sugar lowering, cholesterol reducing have benefit preferably, and nutrient substance is converted into micromolecular compound through enzymolysis, distillation; Be present in the wine, with the paclitaxel combination, wine is guiding drug again; Efficacy enhanced by wine, active substance go directly focus fast and play a role.
(2) paclitaxel oral liquid: the 7500ml distilled water is put into a resistant to elevated temperatures glass container, and indirect 40 degree are put into crystal sugar 500g, add Polyethylene Glycol 45ml after the VC50 sheet stirs and dissolves and stir; Add paclitaxel bullion 5kg again, fully stir 10 minutes after, when treating that its whole alkene are interpreted into pink microemulsion shape; Pour in the container that fills the 40kg propolis, stirred 20 minutes, with it all miscible after; Metering filling, every 10ml, every oral liquid includes paclitaxel bullion 1g; 10 in every box is used UST flash pasteurizer sterilization processing then, promptly becomes the paclitaxel oral liquid.
Treatment usefulness, every day, oral secondary, prevented usefulness, oral 1 time of every day, each 1 by each 1.
The paclitaxel oral liquid utilizes propolis as substrate, and the microemulsion performance is good, and is nutritious, and the effect of adding VC is to reduce the solution peroxidating, long shelf-life, and also mouthfeel is good, is prone to absorb, and effect is fast.
Paclitaxel is the plant extract of finding to have extremely strong active anticancer over nearly 10 years, and it is different from other medicinal plants and chemotherapeutics, and antitumaous effect is extremely unique, and its main mechanism of action is:
Behind paclitaxel and the cell receptor, the TNF-a inhibitive factor that discharges gets in the nucleus through thin blood vessel of tumor neogenetic microtriche and after birth, impels the tumor microtubule polymerization, and does not react with unpolymerized tubulin dimer.Inhibitive factor TNF-a can accumulate a large amount of microtubules in cancerous cell, also be the GFP inhibitive factor.The accumulation of these microtubules is disturbed and has been destroyed the cancerous cell genetic immunization and repairs answering; The cancerous cell division is stopped in the mitotic phase G2/m; Cause quick splitted tumor cell fixing by firmly in the mitotic phase stage; Stoped the very fast growth of cancerous cell and duplicated, and trapped and killed cancerous cell, caused tumor cell atrophy, apoptosis through resisting tubulin and dimer dynamic equilibrium.
The functional effect of paclitaxel is that tumor-suppression activity is the strongest in any botanical anticancer medicine and the alkaloid.The most a kind of cancer drug that presses down, the paclitaxel of especially nontoxic extraction when having guaranteed that the patient takes the back safety, has also strengthened and has pressed down the cancer curative effect.
The specific embodiment
Oral anticancer preparation of the nontoxic extraction paclitaxel of Ramulus et folium taxi cuspidatae Herb and preparation method thereof, its main technique is:
1, extraction process
(1) roguing, O
3Water cleans, and earth and other contaminant removal of 100kg Ramulus et folium taxi cuspidatae Herb dry product surface attachment fallen, and puts into O
3Clean in the water service sink.
(2) cut into slices, after the 100kg Ramulus et folium taxi cuspidatae Herb taking-up after cleaning is drained away the water, be cut into the thick thin slice of 2mm;
(3) oven dry is put into stainless steel disc with the Ramulus et folium taxi cuspidatae thin slice, sends in the hot air circular drying machine of 50 degree oven dry 3 hours, waits to contain moisture 5% when following, taking-up;
(4) pulverize, the Ramulus et folium taxi cuspidatae fragment after the oven dry is pulverized through rustless steel pulverizing machine again, and granularity is below the 1mm;
(5) ultra micro breaking cellular wall is with the 100kg taxus chinensis powder after pulverizing, through nanometer ultra micro wall-breaking machine micronizing 300 orders;
(6) soak with ethanol is peeled off, and adopts 95% medical ethanol 500kg, and Ramulus et folium taxi cuspidatae Herb superfine powder 100kg puts into the rustless steel container that can seal; Indirect 38 degree, constant temperature soaked after 24 hours, was heating 60 degree simultaneously; After continuous stirring was peeled off 20 minutes, desuperheat also stopped to stir.
(7) just filter, the solution after stirring is peeled off filters with the filter membrane of 500 order fineness, and filtering residue filters in the secondary soak with ethanol, and twice filtrating merges.
(8) detoxification treatment is put into a rustless steel container, indirect 50-60 degree with the amalgamation liquid of filter just; Rising gradually along with the liquid temperature; Deleterious lightweight bean China fir volatile spirits floats to ethanol liquid surface on can be progressively, builds up to the center, at this moment with the rustless steel soup ladle it is taken out;
(9) the ultrafilter membrane seperator is adopted in low pressure macropore ultrafiltration, and setting the ultrafiltration granularity is 0.01um, with the pressurization of the alcoholic solution after the detoxification, holds back through low pressure macropore 0.01um ultrafiltration, and trapped substance is a crude fibre, the macromolecular substances of no values such as micronic dust, colloid.
(10) high pressure aperture ultrafiltration is held back low pressure macropore permeate again through the filter membrane ultrafiltration of high pressure aperture 0.001um, trapped fluid is chemical compound macromole liquid such as alkane Diterpenes, and permeate is ethanol and micromolecular compound.
(11) chromatography, with high pressure aperture permeate, through silica gel column chromatography vacuum state infiltration absorption, the trapped fluid with eluent and high pressure aperture merges then.
(12) vacuum infiltration concentrates, and amalgamation liquid is carried out through thickener warm vacuum state infiltration concentrates in 3 hours 40 degree, the paste body shape of macromole after merging.
(13) reclaim ethanol,, distill recycling with distillator with the micromolecule ethanol liquid merging that micromolecule ethanol liquid and the chromatography of vacuum infiltration sees through.
(14) secondary detoxification is poured the spissated mastic of vacuum infiltration in the stainless steel disc of one thin-walled into, sends into sealing in the thermostatic drying chamber of 60 degree, inhales empty dry 6 hours with the vacuum pump batch (-type), and the part ethanol in its paste body shape and volatile oil following temperature rising height are vapored away.
(15) low-temperature vacuum drying is broken the no ethanol half hitch crystal block of substantially dry into pieces, puts into the stainless steel disc of a thin-walled; Send in the vacuum freeze drier; Under the vacuum state more than negative 38 degree, lyophilization promptly became the paclitaxel crystalline solid of nontoxic extraction after 8 hours.
(16) crystalline solid is pulverized, and dried crystalline solid is pulverized 80 orders fast through the rustless steel high speed disintegrator, can get the paclitaxel bullion.
2, the method for preparing of paclitaxel medicated wine
Herba bromi japonici wine 50kg with 38 degree puts into the stainless container of a high capacity, and indirect 40 degree is put into 5kg paclitaxel bullion again, fully stirs 20 minutes, treats it all after the dissolving, with the membrane filtration of 0.1um, and metering filling, every bottle of 250ml.
3, the method for preparing of paclitaxel oral liquid
The 7500ml distilled water is put into a resistant to elevated temperatures glass container, and indirect 40 degree are put into 50 of crystal sugar 500g, vitamin Cs; Stirring is dissolved the back after adding Polyethylene Glycol 45ml, fully stirring 10 minutes, when treating that its whole alkene are interpreted into pink microemulsion shape; Pour in the container that fills the 40kg propolis, stirred 20 minutes, with it all miscible after; Metering filling, every 10ml, every oral liquid contains paclitaxel bullion 1g.
Claims (2)
1. the amalgamation liquid that will just filter is put into a rustless steel container, indirect 50-60 degree, and along with the rising gradually of liquid temperature, deleterious lightweight bean China fir volatile spirits floats to the ethanol surface on can be progressively, and builds up to the center, at this moment with the rustless steel soup ladle it is taken out.
2. the spissated mastic of vacuum infiltration is poured in the stainless steel disc of a thin-walled, is sent into sealing in the thermostatic drying chamber of 60 degree, inhale empty dry 6 hours with the vacuum pump batch (-type) after, the intravital part ethanol of its cream and volatile spirits following temperature rising height are vapored away.
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| CN102827749A (en) * | 2012-09-21 | 2012-12-19 | 林树芳 | Ornithogalum saponins and paclitaxel health care liquor |
| CN104059034A (en) * | 2014-06-06 | 2014-09-24 | 庞作仁 | Production system and process for nontoxically extracting taxol through ultrasonic wave countercurrent extraction |
| CN104970087A (en) * | 2014-04-11 | 2015-10-14 | 信阳农林学院 | Egg preservative agent from metasequoia seeds and preparation technology thereof |
| CN105380869A (en) * | 2015-12-28 | 2016-03-09 | 深圳中农科工创业资产管理有限公司 | Nano Taxus chinensis skin care product and application thereof |
| CN105541761A (en) * | 2015-12-28 | 2016-05-04 | 深圳中农科工创业资产管理有限公司 | Paclitaxel crystal and preparation method of medicinal liquor and oral liquid of paclitaxel crystal |
| CN105647754A (en) * | 2014-12-15 | 2016-06-08 | 仁怀市益康红豆杉专业合作社 | Preparation method of compound Chinese yew wine |
| CN111559729A (en) * | 2020-03-25 | 2020-08-21 | 普洱大华林业科技有限公司 | Production filling device for drinking wine by using Chinese yew fruit percolation |
| CN113101336A (en) * | 2021-04-26 | 2021-07-13 | 庞中龙 | Method and process for preparing compound paclitaxel anti-breast cancer capsule tablet |
| CN114306270A (en) * | 2021-04-22 | 2022-04-12 | 庞作仁 | Compound taxol capsule and tablet preparation method and process |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102827749A (en) * | 2012-09-21 | 2012-12-19 | 林树芳 | Ornithogalum saponins and paclitaxel health care liquor |
| CN104970087A (en) * | 2014-04-11 | 2015-10-14 | 信阳农林学院 | Egg preservative agent from metasequoia seeds and preparation technology thereof |
| CN104059034A (en) * | 2014-06-06 | 2014-09-24 | 庞作仁 | Production system and process for nontoxically extracting taxol through ultrasonic wave countercurrent extraction |
| CN105647754A (en) * | 2014-12-15 | 2016-06-08 | 仁怀市益康红豆杉专业合作社 | Preparation method of compound Chinese yew wine |
| CN105380869A (en) * | 2015-12-28 | 2016-03-09 | 深圳中农科工创业资产管理有限公司 | Nano Taxus chinensis skin care product and application thereof |
| CN105541761A (en) * | 2015-12-28 | 2016-05-04 | 深圳中农科工创业资产管理有限公司 | Paclitaxel crystal and preparation method of medicinal liquor and oral liquid of paclitaxel crystal |
| CN111559729A (en) * | 2020-03-25 | 2020-08-21 | 普洱大华林业科技有限公司 | Production filling device for drinking wine by using Chinese yew fruit percolation |
| CN114306270A (en) * | 2021-04-22 | 2022-04-12 | 庞作仁 | Compound taxol capsule and tablet preparation method and process |
| CN113101336A (en) * | 2021-04-26 | 2021-07-13 | 庞中龙 | Method and process for preparing compound paclitaxel anti-breast cancer capsule tablet |
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Application publication date: 20120711 |