CN101474164A - Oral compound paclitaxel capsule and preparation method - Google Patents
Oral compound paclitaxel capsule and preparation method Download PDFInfo
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- CN101474164A CN101474164A CNA2008102300170A CN200810230017A CN101474164A CN 101474164 A CN101474164 A CN 101474164A CN A2008102300170 A CNA2008102300170 A CN A2008102300170A CN 200810230017 A CN200810230017 A CN 200810230017A CN 101474164 A CN101474164 A CN 101474164A
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Abstract
The invention relates to a capsule improving the oral bioavailability of taxol for treating cancer and a preparation method thereof. The invention is characterized in that the content of the capsule is solid; the content comprises 80-99wt% of taxol clathrate compound and 1-20wt% of hanfangchin A; the taxol clathrate compound mainly prepared by cyclodextrin and taxol, and hydroxypropyl-beta-cyclodextrin is the best choice; and the molar ratio of the hydroxypropyl-beta-cyclodextrin to the taxol is 1:10-1:60. The invention aims at changing the multidrug resistance phenomenon of existing clinical antitumor medicament and improving the oral bioavailability of the taxol, alleviating adverse effects and increasing the clinical utilization rate of the taxol simultaneously, and thereby, the cancer treating effect of medicament is improved.
Description
Technical field: the present invention relates to the preparation field of medicine, especially a kind of capsule that has improved oral bioavailability of taxol for treating cancer and preparation method thereof.
Background technology: cancer harm humans health has become and has caused one of human dead principal disease, with viral disease, Senile disease and be called three challenges greatly of modern medicine.
The main pharmacologically active of paclitaxel is an antitumor, the clinical ovarian cancer that is used for the treatment of, mastocarcinoma, pulmonary carcinoma and nasopharyngeal carcinoma.Its mechanism of action is can combine with the cell tubulin when cell division, makes to form stable microtubule fasolculus in the cell, and with G-2 mitosis in interference cell cycle, thus the growth of inhibition tumor cell.The dose limitation toxicity of paclitaxel is mainly neurotoxicity, bone marrow depression and heart and Toxicity of Kidney.
Paclitaxel is insoluble in water, and oral administration biaavailability is extremely low.Existing formulation for paclitaxel (the Paclitaxel that is used for chemotherapy
) be that paclitaxel is dissolved in polyoxyethylene castor oil (Cremphor
EL) with the mixed liquor of dehydrated alcohol 1:1 in, concentration is 7mmol/L, is diluted to final concentration 0.35～1.4mmol/L with 0.9% normal saline or 5% Glucose Liquid before the administration.When medication, need use a series of filters, to prevent with in some granule injection bodies.The dosage regimen of paclitaxel is 3h of per three weeks or 24h intravenous injections, and dose is 135 or 175mg/m
2Paclitaxel can also be by vein and abdominal cavity infusion administration in addition.
Though paclitaxel injection has obtained using widely, still there are a lot of deficiencies in it.1, stability and water solublity are relatively poor; 2, incompatible with the defeated people's equipment of some vein; 3, severe anaphylactic reaction (can discharge histamine when mainly being the polyoxyethylene castor oil degradation in vivo in the double solvent, severe anaphylactic reaction can take place, clinical need be by taking steroid hormone and H to the patient in advance
1And H
2Receptor antagonist or prolongation infusion time overcome the generation of untoward reaction); 4, even more serious be paclitaxel in clinical antineoplaston, multidrug resistance occurred, and caused the failure for the treatment of.
Oral administration is the route of administration of most convenient, and there is the problem of bioavailability extreme difference when oral in paclitaxel (TAX), is difficult to the oral administration administration.Bibliographical information owing to have P-gp (P glycoprotein inhibitors) on the gastrointestinal tract epithelial cell film, causes paclitaxel to be pumped out tumor cell, the multidrug resistance phenomenon of antitumor drug clinically occurs.
Summary of the invention:
Goal of the invention: the invention provides a kind of oral compound paclitaxel capsule and preparation method, its purpose is to improve the dissolubility and the stability of paclitaxel oral medicine, and reaches the problem of heightening the paclitaxel oral administration biaavailability and overcoming aspect existence such as paclitaxel multidrug resistance by administering drug combinations.
Technical scheme: the present invention is achieved through the following technical solutions:
A kind of oral compound paclitaxel capsule, be used for the treatment of ovarian cancer, mastocarcinoma, pulmonary carcinoma and nasopharyngeal carcinoma, it is characterized in that: the content of described capsule is solid-state, form by included taxol and tetrandrine, wherein the component of included taxol accounts for 80～99% of total content quality, tetrandrine component account for 1～20% of total content quality;
Described included taxol is made up of cyclodextrin and paclitaxel, and the mol ratio of cyclodextrin and paclitaxel is cyclodextrin: paclitaxel=1:10～1:60; Cyclodextrin is wherein selected alpha-cyclodextrin, beta-schardinger dextrin-, hydroxypropyl-beta-schardinger dextrin-, ethoxy-beta-schardinger dextrin-, dimethyl-beta-schardinger dextrin-, single succinyl-dimethyl-beta-schardinger dextrin-for use, is methylated at random-beta-schardinger dextrin-, 6-carboxymethyl-beta-schardinger dextrin-, gamma-cyclodextrin.
Cyclodextrin is selected hydroxypropyl-beta-schardinger dextrin-for use.
It is dissolved with hydrophilicity condiment or cosolvent selecting HP-for use, and wherein hydrophilicity condiment is a kind of in polyvinylpyrrolidone, hydroxypropyl methylcellulose, the sodium carboxymethyl cellulose; Described cosolvent is a Polyethylene Glycol-400, a kind of in the propylene glycol.
The concentration of described hydrophilicity condiment or cosolvent is 1～10% (m/v).
A kind of preparation method of aforesaid oral compound paclitaxel capsule is characterized in that: this method is to carry out according to the following steps:
The preparation of a, included taxol:
Choose cyclodextrin, paclitaxel, mol ratio is 1:10～1:60; With the aqueous solution dissolving of cyclodextrin with hydrophilicity condiment or cosolvent, with the paclitaxel anhydrous alcohol solution, dropwise add paclitaxel solution in the cyclodextrin solution, stirred 2～4 hours down at 25～70 ℃, with the settled solution that obtained through filtering with microporous membrane, subsequent filtrate is pre-freeze in-40～-80 ℃ of refrigerators, takes out through the vacuum freeze drier lyophilization and gets included taxol after 24～72 hours, and is standby; Cyclodextrin is wherein selected alpha-cyclodextrin, hydroxypropyl-beta-schardinger dextrin-, ethoxy-beta-schardinger dextrin-, dimethyl-beta-schardinger dextrin-, single succinyl-dimethyl-beta-schardinger dextrin-for use, is methylated at random-beta-schardinger dextrin-, 6-carboxymethyl-beta-schardinger dextrin-, gamma-cyclodextrin;
B, the capsular preparation of compound paclitaxel:
Under 100,000 grades of conditions of cleanliness factor, account for 80～99% of total content quality by the component of included taxol, 1～20% mixed that the component of tetrandrine accounts for total content quality is even, incapsulates after sieving, and makes.
Cyclodextrin is selected hydroxypropyl-beta-schardinger dextrin-for use.
Described hydrophilicity condiment is a kind of in polyvinylpyrrolidone, hydroxypropyl methylcellulose, the sodium carboxymethyl cellulose; Described cosolvent is a Polyethylene Glycol-400, a kind of in the propylene glycol; The concentration of hydrophilicity condiment or cosolvent is 1～10%.
In step a with the settled solution that obtained through 0.45 μ m filtering with microporous membrane.
In step b, cross 60～100 mesh sieves.
Preparation method to beta-schardinger dextrin-is: accurately measure 10 parts of beta-schardinger dextrin-s, make saturated solution with the dissolving of 10% Polyethylene Glycol-400 aqueous solution, take by weighing 1 part of paclitaxel with anhydrous alcohol solution after, dropwise add in β-CD solution, 600 rev/mins of fixed rotating speeds, in 50 ℃ of magnetic agitation 4 hours,, filter institute's standing over night, precipitation gets included taxol with distilled water, ether washing after dry 72 hours;
After according to the mass ratio of paclitaxel api: tetrandrine=1:10 included taxol and tetrandrine crude drug being crossed 80 mesh sieves, mix back encapsulating capsule according to the principle that equivalent is progressively increased.
Advantage and effect: the invention provides a kind of oral compound paclitaxel capsule and preparation method, the dissolubility and the stability of paclitaxel have been characterized in improving, and, reach the purpose of heightening the paclitaxel oral administration biaavailability and overcoming the paclitaxel multidrug resistance by associating tetrandrine administering drug combinations.It is raw material that this capsule mainly adopts included taxol, the advantage of included taxol is to compare with the paclitaxel api physical mixture with simple employing paclitaxel api in the past, its dissolution improves, particularly paclitaxel mixes with hydroxypropyl, dissolution improves greatly, has so also just improved its bioavailability greatly, but has made it to become oral absorption, seek the P-gp inhibitor again, the compound recipe novel formulation that both form associating is expected to prolong or avoid the multidrug resistance of TAX.It is model drug that this research is intended to the antineoplastic agent paclitaxel, be equipped with from Chinese medicine effective active composition, filter out P-gp inhibitor---tetrandrine, make The combined form a brand-new antineoplastic prescription, also improve the paclitaxel oral administration biaavailability simultaneously with the multidrug resistance phenomenon that changes present clinical tumor medicine, reduce untoward reaction, improve the clinical utilization rate of paclitaxel, thereby improved the effect of the treatment cancer of medicine.
Description of drawings:
Fig. 1 is the dissolution comparison diagram of paclitaxel api, paclitaxel api and cyclodextrin physical mixture and included taxol in the HCl of 200mL 0.1M;
Fig. 2 paclitaxel injection (5mg/kg) and compound paclitaxel capsule (10mg/kg) are at the intravital plasma concentration curve figure of rat.
The specific embodiment: following the present invention will be further described:
The present invention designs by scientific technology, paclitaxel is made the big included taxol of water solublity, and then it is mixed with into capsule with tetrandrine, its purpose is to improve the dissolubility and the stability of paclitaxel, and reaches the purpose of heightening the paclitaxel oral administration biaavailability and overcoming the paclitaxel multidrug resistance by associating tetrandrine administering drug combinations.
Embodiment 1: prepare compound paclitaxel capsule according to the following steps:
Accurately measure 60 parts with hydroxypropyl-beta-schardinger dextrin-(HP-β-CD), 1 part of paclitaxel, HP-β-CD dissolves with 0.1% polyvinylpyrrolidone (PVP) aqueous solution, the paclitaxel anhydrous alcohol solution, drug solution is dropwise added in HP-β-CD solution, fixed rotating speed 400rpm, stir 2h in 25 ℃ of lower magnetic forces, with the settled solution that obtained through 0.45 μ m filtering with microporous membrane pre-freeze in-40 ℃ of refrigerators, put behind the vacuum freeze drier lyophilization 24h included taxol.
With recipe quantity included taxol and tetrandrine crude drug (paclitaxel api: tetrandrine=1:1, m/m) cross 60 mesh sieves after, mix back encapsulating capsule according to the principle that equivalent is progressively increased.
Embodiment 2: prepare compound paclitaxel capsule according to the following steps:
Accurately measure HP-β-CD of 50 parts, 1 part of paclitaxel, HP-β-CD dissolves with 10% aqueous solution of propylene glycol, the paclitaxel dissolve with ethanol, drug solution is dropwise added in HP-β-CD solution, fixed rotating speed 500rpm, stir 3h in 40 ℃ of lower magnetic forces, with the settled solution that obtained through 0.45 μ m filtering with microporous membrane pre-freeze in-60 ℃ of refrigerators, put behind the vacuum freeze drier lyophilization 48h included taxol.
With recipe quantity included taxol and tetrandrine crude drug (paclitaxel api: tetrandrine=1:2, m/m) cross 80 mesh sieves after, mix back encapsulating capsule according to the principle that equivalent is progressively increased.
Embodiment 3: prepare compound paclitaxel capsule according to the following steps:
Accurately measure dimethyl-beta-schardinger dextrin-(DM-β-CD), 1 part of paclitaxel of 40 parts (mol ratios), dimethyl-beta-schardinger dextrin-(DM-β-CD) with the dissolving of 0.1%HPMC aqueous solution, the paclitaxel dissolve with ethanol, drug solution is dropwise added dimethyl-beta-schardinger dextrin-(in the solution of DM-β-CD), fixed rotating speed 600rpm, stir 4h in 50 ℃ of lower magnetic forces, with the settled solution that obtained through 0.45 μ m filtering with microporous membrane pre-freeze in-80 ℃ of refrigerators, put behind the vacuum freeze drier lyophilization 72h included taxol.
With recipe quantity included taxol and tetrandrine crude drug (paclitaxel api: tetrandrine=1:5, m/m) cross 100 mesh sieves after, mix back encapsulating capsule according to the principle that equivalent is progressively increased.
Embodiment 4: prepare compound paclitaxel capsule according to the following steps:
Accurately measure 30 parts methylate at random-beta-schardinger dextrin-(RM-β-CD), 1 part of paclitaxel, (RM-β-CD) dissolve with 0.1% CMC-Na aqueous solution at random methylates-beta-schardinger dextrin-, the paclitaxel dissolve with ethanol, drug solution dropwise added at random methylate-beta-schardinger dextrin-is (in the solution of RM-β-CD), fixed rotating speed 700rpm, stir 2h in 60 ℃ of lower magnetic forces, with the settled solution that obtained through 0.45 μ m filtering with microporous membrane pre-freeze in-40 ℃ of refrigerators, put behind the vacuum freeze drier lyophilization 24h included taxol.
With recipe quantity included taxol and tetrandrine crude drug (paclitaxel api: tetrandrine=1:10, m/m) cross 60 mesh sieves after, mix back encapsulating capsule according to the principle that equivalent is progressively increased.
Embodiment 5: prepare compound paclitaxel capsule according to the following steps:
Accurately measure single succinyl-dimethyl-beta-schardinger dextrin-(SDM-β-CD) of 20 parts, 1 part of paclitaxel, single succinyl-dimethyl-beta-schardinger dextrin-(SDM-β-CD) dissolve with 10% PEG-400 aqueous solution, the paclitaxel dissolve with ethanol, drug solution is dropwise added single succinyl-dimethyl-beta-schardinger dextrin-(in the solution of SDM-β-CD), fixed rotating speed 800rpm, stir 3h in 70 ℃ of lower magnetic forces, with the settled solution that obtained through 0.45 μ m filtering with microporous membrane pre-freeze in-60 ℃ of refrigerators, put behind the vacuum freeze drier lyophilization 48h included taxol.
With recipe quantity included taxol and tetrandrine crude drug (paclitaxel api: tetrandrine=1:1, m/m) cross 80 mesh sieves after, mix back encapsulating capsule according to the principle that equivalent is progressively increased.
Embodiment 6: prepare compound paclitaxel capsule according to the following steps:
Accurately measure ethoxy-beta-schardinger dextrin-(HE-β-CD), 1 part of paclitaxel of 10 parts, ethoxy-beta-schardinger dextrin-(HE-β-CD) dissolve with 0.01% CMC-Na aqueous solution, the paclitaxel dissolve with ethanol, drug solution is dropwise added ethoxy-beta-schardinger dextrin-(in the solution of HE-β-CD), fixed rotating speed 400rpm, stir 4h in 25 ℃ of lower magnetic forces, with the settled solution that obtained through 0.45 μ m filtering with microporous membrane pre-freeze in-80 ℃ of refrigerators, put behind the vacuum freeze drier lyophilization 72h included taxol.
With recipe quantity included taxol and tetrandrine crude drug (paclitaxel api: tetrandrine=1:2, m/m) cross 100 mesh sieves after, mix back encapsulating capsule according to the principle that equivalent is progressively increased.
Embodiment 7: prepare compound paclitaxel capsule according to the following steps:
Accurately measure 6-carboxymethyl-beta-schardinger dextrin-(SBE-β-CD), 1 part of paclitaxel of 20 parts, 6-carboxymethyl-beta-schardinger dextrin-(SBE-β-CD) dissolve with 0.01% PVP aqueous solution, the paclitaxel dissolve with ethanol, drug solution is dropwise added 6-carboxymethyl-beta-schardinger dextrin-(in the solution of SBE-β-CD), fixed rotating speed 500rpm, stir 2h in 40 ℃ of lower magnetic forces, with the settled solution that obtained through 0.45 μ m filtering with microporous membrane pre-freeze in-40 ℃ of refrigerators, put behind the vacuum freeze drier lyophilization 24h included taxol.
With recipe quantity included taxol and tetrandrine crude drug (paclitaxel api: tetrandrine=1: 5, m/m) cross 60 mesh sieves after, mix back encapsulating capsule according to the principle that equivalent is progressively increased.
Embodiment 8: prepare compound paclitaxel capsule according to the following steps:
Accurately measure 10 parts of β-CD, make saturated solution with the dissolving of 10% PEG-400 aqueous solution, take by weighing 1 part of paclitaxel with anhydrous alcohol solution after, dropwise add in β-CD solution, fixed rotating speed 600rpm, in 50 ℃ of magnetic agitation 4h,, filter institute's standing over night, precipitation gets included taxol with distilled water, ether washing behind the dry 72h.
With recipe quantity included taxol and tetrandrine crude drug (paclitaxel api: tetrandrine=1:10, m/m) cross 80 mesh sieves after, mix back encapsulating capsule according to the principle that equivalent is progressively increased.
The experiment proved that, the cyclodextrin of choosing is selected alpha-cyclodextrin, beta-schardinger dextrin-, hydroxypropyl-beta-schardinger dextrin-, ethoxy-beta-schardinger dextrin-, dimethyl-beta-schardinger dextrin-, single succinyl-dimethyl-beta-schardinger dextrin-for use, is methylated at random-beta-schardinger dextrin-, 6-carboxymethyl-beta-schardinger dextrin-, gamma-cyclodextrin can reach purpose of the present invention as the enclose material, but select for use hydroxypropyl-beta-schardinger dextrin-for best, its dissolubility is 2～80 times of other enclose material.
As shown in Figure 1, be the dissolution comparison diagram of the present invention's paclitaxel api, paclitaxel api and cyclodextrin physical mixture and included taxol in 200mL 0.1M HCl; It is the dissolution test of paclitaxel-HP-.Carry out the result of the dissolution investigation of medicine by 2005 editions two appendix dissolution method three therapeutic methods of traditional Chinese medicine of Chinese Pharmacopoeia; By this figure as seen, the dissolution rate of paclitaxel api is the slowest, stripping accumulative total percentage dissolution is less than 5% in 150min, and the dissolution of physical mixture in water of paclitaxel and HP-β-CD increases than the dissolution of paclitaxel api, but in the 150min still less than 10%.And China fir alcohol clathrate out-degree is greater than 85% when 45min, stripping reaches more than 90% behind the 1h, dissolution rate obviously improves.
As shown in Figure 2, for paclitaxel injection (5mg/kg) and compound paclitaxel capsule (10mg/kg) at the intravital plasma concentration curve of rat.Handle to such an extent that the capsular absolute bioavailability of compound paclitaxel is about 25% with DAS software to the moving data of gained medicine, C
Max=0.584 ± 0.145 μ g/mL, T
Max=2.25 ± 0.88h.Experimental result shows, this preparation has significantly improved its oral administration biaavailability (when paclitaxel api rat dosage reaches 20 times of bio-occlusion pharmaceutical quantities, still not having absorption) when increasing taxol solubility.
This capsule that is used for the treatment of cancer has changed the multidrug resistance phenomenon of present clinical tumor medicine and has improved the paclitaxel oral administration biaavailability simultaneously, reduces untoward reaction, improves the clinical utilization rate of paclitaxel, thereby has improved the effect of the treatment cancer of medicine.
Claims (10)
1, a kind of oral compound paclitaxel capsule, be used for the treatment of ovarian cancer, mastocarcinoma, pulmonary carcinoma and nasopharyngeal carcinoma, it is characterized in that: the content of described capsule is solid-state, form by included taxol and tetrandrine, wherein the component of included taxol accounts for 80～99% of total content quality, tetrandrine component account for 1～20% of total content quality;
Described included taxol is made up of cyclodextrin and paclitaxel, and the mol ratio of cyclodextrin and paclitaxel is cyclodextrin: paclitaxel=1:10～1:60; Cyclodextrin is wherein selected alpha-cyclodextrin, beta-schardinger dextrin-, hydroxypropyl-beta-schardinger dextrin-, ethoxy-beta-schardinger dextrin-, dimethyl-beta-schardinger dextrin-, single succinyl-dimethyl-beta-schardinger dextrin-for use, is methylated at random-beta-schardinger dextrin-, 6-carboxymethyl-beta-schardinger dextrin-, gamma-cyclodextrin.
2, a kind of oral compound paclitaxel capsule according to claim 1, it is characterized in that: cyclodextrin is selected hydroxypropyl-beta-schardinger dextrin-for use.
3, a kind of oral compound paclitaxel capsule according to claim 1 and 2, it is characterized in that: it is dissolved with hydrophilicity condiment or cosolvent selecting HP-for use, and wherein hydrophilicity condiment is a kind of in polyvinylpyrrolidone, hydroxypropyl methylcellulose, the sodium carboxymethyl cellulose; Described cosolvent is a Polyethylene Glycol-400, a kind of in the propylene glycol.
4, a kind of oral compound paclitaxel capsule according to claim 1 is characterized in that: the concentration of described hydrophilicity condiment or cosolvent is 1～10% (m/v).
5, a kind of preparation method of oral compound paclitaxel capsule as claimed in claim 1 is characterized in that: this method is to carry out according to the following steps:
The preparation of a, included taxol:
Choose cyclodextrin, paclitaxel, mol ratio is 1:10～1:60; With the aqueous solution dissolving of cyclodextrin with hydrophilicity condiment or cosolvent, with the paclitaxel anhydrous alcohol solution, dropwise add paclitaxel solution in the cyclodextrin solution, stirred 2～4 hours down at 25～70 ℃, with the settled solution that obtained through filtering with microporous membrane, subsequent filtrate is pre-freeze in-40～-80 ℃ of refrigerators, takes out through the vacuum freeze drier lyophilization and gets included taxol after 24～72 hours, and is standby; Cyclodextrin is wherein selected alpha-cyclodextrin, hydroxypropyl-beta-schardinger dextrin-, ethoxy-beta-schardinger dextrin-, dimethyl-beta-schardinger dextrin-, single succinyl-dimethyl-beta-schardinger dextrin-for use, is methylated at random-beta-schardinger dextrin-, 6-carboxymethyl-beta-schardinger dextrin-, gamma-cyclodextrin;
B, the capsular preparation of compound paclitaxel:
Under 100,000 grades of conditions of cleanliness factor, account for 80～99% of total content quality by the component of included taxol, 1～20% mixed that the component of tetrandrine accounts for total content quality is even, incapsulates after sieving, and makes.
6, the preparation method of a kind of oral compound paclitaxel capsule according to claim 4, it is characterized in that: cyclodextrin is selected hydroxypropyl-beta-schardinger dextrin-for use.
7, the preparation method of a kind of oral compound paclitaxel capsule according to claim 4 is characterized in that: described hydrophilicity condiment is a kind of in polyvinylpyrrolidone, hydroxypropyl methylcellulose, the sodium carboxymethyl cellulose; Described cosolvent is a Polyethylene Glycol-400, a kind of in the propylene glycol; The concentration of hydrophilicity condiment or cosolvent is 1～10%.
8, the preparation method of a kind of oral compound paclitaxel capsule according to claim 4 is characterized in that: in step a with the settled solution that obtained through 0.45 μ m filtering with microporous membrane.
9, the preparation method of a kind of oral compound paclitaxel capsule according to claim 4 is characterized in that: cross 60～100 mesh sieves in step b.
10, the preparation method of a kind of oral compound paclitaxel capsule according to claim 4, it is characterized in that: the preparation method to beta-schardinger dextrin-is: accurately measure 10 parts of beta-schardinger dextrin-s, make saturated solution with the dissolving of 10% Polyethylene Glycol-400 aqueous solution, take by weighing 1 part of paclitaxel with anhydrous alcohol solution after, dropwise add in the beta-schardinger dextrin-solution, 600 rev/mins of fixed rotating speeds, in 50 ℃ of magnetic agitation 4 hours, with institute's standing over night, filter, precipitation gets included taxol with distilled water, ether washing after dry 72 hours;
After according to the mass ratio of paclitaxel api: tetrandrine=1:10 included taxol and tetrandrine crude drug being crossed 80 mesh sieves, mix back encapsulating capsule according to the principle that equivalent is progressively increased.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302786A (en) * | 2011-08-01 | 2012-01-04 | 扬州大学 | Preparation method for beta-cyclodextrin polymer-paclitaxel inclusion compound |
| CN102579402A (en) * | 2012-03-26 | 2012-07-18 | 山东大学 | Preparation method for vesica of load paclitaxel |
| CN104173461A (en) * | 2014-09-07 | 2014-12-03 | 成都市飞龙水处理技术研究所 | Medicine for oral administration for treating undifferentiated carcinoma (intranasal) and preparation method thereof |
| CN114306270A (en) * | 2021-04-22 | 2022-04-12 | 庞作仁 | Compound taxol capsule and tablet preparation method and process |
-
2008
- 2008-12-22 CN CNA2008102300170A patent/CN101474164A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102302786A (en) * | 2011-08-01 | 2012-01-04 | 扬州大学 | Preparation method for beta-cyclodextrin polymer-paclitaxel inclusion compound |
| CN102579402A (en) * | 2012-03-26 | 2012-07-18 | 山东大学 | Preparation method for vesica of load paclitaxel |
| CN102579402B (en) * | 2012-03-26 | 2013-07-03 | 山东大学 | Preparation method for vesica of load paclitaxel |
| CN104173461A (en) * | 2014-09-07 | 2014-12-03 | 成都市飞龙水处理技术研究所 | Medicine for oral administration for treating undifferentiated carcinoma (intranasal) and preparation method thereof |
| CN114306270A (en) * | 2021-04-22 | 2022-04-12 | 庞作仁 | Compound taxol capsule and tablet preparation method and process |
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