CN103142522B - Etoposide tablet - Google Patents
Etoposide tablet Download PDFInfo
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- CN103142522B CN103142522B CN201310092429.3A CN201310092429A CN103142522B CN 103142522 B CN103142522 B CN 103142522B CN 201310092429 A CN201310092429 A CN 201310092429A CN 103142522 B CN103142522 B CN 103142522B
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- etoposide
- tablet
- clathrate
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- cyclodextrin
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- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 title claims abstract description 59
- 229960005420 etoposide Drugs 0.000 title claims abstract description 59
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 13
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 7
- 229920002472 Starch Polymers 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 3
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 3
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 3
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 3
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 abstract 3
- 230000000052 comparative effect Effects 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 12
- 239000002671 adjuvant Substances 0.000 description 11
- 238000004090 dissolution Methods 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 2
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000005352 clarification Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000010316 high energy milling Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000012982 microporous membrane Substances 0.000 description 2
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 2
- 229960001237 podophyllotoxin Drugs 0.000 description 2
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000013521 mastic Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to an etoposide inclusion compound tablet. The etoposide is prepared into an inclusion compound, and then the inclusion compound is prepared into the tablet.
Description
Technical field
The application relates to a kind of tablet, particularly, is etoposide clathrate tablet.
Background technology
Etoposide (etoposide) is the carbohydrate metabolism product of podophyllotoxin (podophyllotoxin), belongs to cell cycle specific antitumor drug, is mainly used in treating small cell lung cancer, lymphatic cancer etc.But the absolute bioavailability of etoposide oral formulations only has 25%～75%.The poorly water-soluble of etoposide and to be decomposed into non-activity product in acid medium be the main cause that causes its oral formulations bioavailability low.
Etoposide mainly contains the dosage forms such as tablet, capsule, injection at present for clinical, and these dosage forms are poor at gastrointestinal tract dissolution, and bioavailability is not high.CN101259100A discloses a kind of etoposide preparations, wherein etoposide is prepared into phosphatide complexes, is then being prepared into the multiple dosage forms such as tablet, capsule.But this preparation cost is high, bioavailability is low, can not be advantageously applied to clinical.
Summary of the invention
The present invention, in order to solve the low shortcoming of existing etoposide preparations bioavailability, has invented etoposide clathrate tablet.
Clathrate has the following advantages: cover bad stink, reduce zest; Increase drug dissolution and bioavailability; Improve medicine stability.
Applicant finds, now etoposide is prepared into clathrate, then is prepared into tablet in conjunction with specific adjuvant, has advantages of that stability is high, disintegration rate is fast and bioavailability is high.
The application provides a kind of tablet of etoposide, comprising:
Etoposide clathrate comprises active component and enclose material, and active component is etoposide, and enclose material is hydroxypropylβ-cyclodextrin.The part by weight of active component and enclose material is 3:1-1:3, preferably 1:2.Experiment showed, alpha-cyclodextrin, beta-schardinger dextrin-, the clathrate that the etoposide clathrate that hydroxyl beta-schardinger dextrin-prepares prepares inferior to hydroxypropylβ-cyclodextrin in aspect effects such as disintegration rate, stability, dissolutions far away.
The impact of different enclose materials on etoposide clathrate
| Enclose material | Dissolution velocity (min) | Stability | Inclusion rate |
| Alpha-cyclodextrin | 12 | Generally | 80% |
| Beta-schardinger dextrin- | 14 | Generally | 82% |
| Hydroxyl beta-schardinger dextrin- | 12 | Generally | 78% |
| Hydroxypropylβ-cyclodextrin | 5 | Good | 93% |
Test method is with reference to the method for two regulations of 2010 editions Chinese Pharmacopoeias.
In this application, select specific adjuvant to prepare etoposide clathrate tablet.Wherein said filler is the compositions of lactose and microcrystalline Cellulose, the two part by weight is 7:2.3, binding agent is selected from methylcellulose or polyvidone, disintegrating agent is the compositions of polyvinylpolypyrrolidone and carboxymethyl starch sodium, the two part by weight is 3:4.5, and lubricant is selected from micropowder silica gel or Pulvis Talci.Experimental results show that, be not that the conventional adjuvant of any pharmacy is all applicable to preparing etoposide clathrate tablet, select the etoposide clathrate tablet that this specific adjuvant prepares to be better than in the effect of the aspects such as disintegration rate, stability, dissolution the etoposide clathrate tablet that other adjuvants prepare far away.
The preparation method of etoposide clathrate comprises:
(1) in water or aquiferous ethanol medium, by a certain percentage, etoposide is reacted with hydroxypropylβ-cyclodextrin, gained solution, through extremely clarification of filtering with microporous membrane, is isolated to clathrate from mixture; Or
(2), with solid form, etoposide is reacted with hydroxypropylβ-cyclodextrin; Or
(3) etoposide reacts with hydroxypropylβ-cyclodextrin and carries out high energy milling.
Metering of the present invention is weight.
Preferably, the prescription of tablet is (by weight):
Embodiment 1 writes out a prescription
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method:
1. prepare by the following method etoposide clathrate:
(1) in water or aquiferous ethanol medium, by a certain percentage, etoposide is reacted with hydroxypropylβ-cyclodextrin, gained solution, through extremely clarification of filtering with microporous membrane, is isolated to clathrate from mixture; Or
(2), with solid form, etoposide is reacted with hydroxypropylβ-cyclodextrin; Or
(3) etoposide reacts with hydroxypropylβ-cyclodextrin and carries out high energy milling.
2. etoposide clathrate was pulverized to 100 mesh sieves, all the other adjuvants were pulverized to 80 mesh sieves; Accurately take the supplementary material of recipe quantity, mix homogeneously (except micropowder silica gel), the alcoholic solution of 3% polyvinylpyrrolidone 95% is granulated, 18 mesh sieve granulate, 40 ℃ are dry.Add the micropowder silica gel of recipe quantity, mix homogeneously, crosses 18 mesh sieves, measures granule drug content, determines sheet weight, and tabletting, obtains.Gained tablet is limited to 48 seconds while disperseing.Embodiment 2 writes out a prescription
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 49 seconds while disperseing.
Embodiment 3
Etoposide described in embodiment 1 and hydroxypropylβ-cyclodextrin are fully ground to and form even mastic in 50% ethanol, after vacuum drying white powder, in the water of this powder solubility property more not the etoposide of enclose improved 12 times.
Comparative example 1
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 142 seconds while disperseing.
Comparative example 2
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 152 seconds while disperseing.
Comparative example 3
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 169 seconds while disperseing.
Comparative example 4
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 192 seconds while disperseing.
Comparative example 5
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 135 seconds while disperseing.
Comparative example 6
Etoposide clathrate: etoposide: hydroxypropylβ-cyclodextrin is 1:2
Preparation method is the same.Gained tablet is limited to 210 seconds while disperseing.
Etoposide tablet dispersing uniformity and Their Dissolution Test in vitro
(1) according to the method for two regulations of 2010 editions Chinese Pharmacopoeias, get each 6 of embodiment 1,2 and comparative example 1-6 tablet, put in 250ml beaker, add the water 100ml of approximately 20 ℃, jolting.All disintegrate is also by No. two sieves in 2 minutes for embodiment 1,2 tablets, and the 3 minute time limit stipulating than pharmacopeia shortens 100%.The jolting of comparative example 1-6 tablet is all disintegrates by No. two sieves after 7 minutes.
(2) Dissolution Rate Testing result shows: according to dissolution method (2010 editions two appendix XC the second methods of Chinese Pharmacopoeia), using 0.01mol/L hydrochloric acid solution 900ml as dissolution medium, rotating speed is 50 revs/min, operation in accordance with the law, according to ultraviolet visible spectrophotometry, measure every stripping quantity, result be the stripping percentage rate of embodiment 1,2 tablets in 50 seconds in about 80-90%, substantially whole strippings in 90 seconds.Comparative example 1-6 sheet stripping percentage rate after 3 minutes is in 20% left and right, substantially whole in 7 minutes
Stripping.The results are shown in following table 1. and table 2.
Table 1 disperses the time limit
| Sample | Disperse the time limit (second) |
| Embodiment 1 | 48 |
| Embodiment 2 | 49 |
| Comparative example 1 | 142 |
| Comparative example 2 | 152 |
| Comparative example 3 | 169 |
| Comparative example 4 | 192 |
| Comparative example 5 | 135 |
| Comparative example 6 | 210 |
Table 2 stripping percentage rate
Experimental data by table 1 and table 2 can find out, adopted dispersibility and the dissolution optimum of the etoposide tablet (embodiment 1 and embodiment 2) that specific adjuvant prepares.
The filler type of selecting in comparative example 1 does not change, but in the compositions of lactose and microcrystalline Cellulose, the part by weight of the two changes, the disintegrating agent type of selecting in comparative example 2 does not change, but in the compositions of polyvinylpolypyrrolidone and carboxymethyl starch sodium, the part by weight of the two changes, in comparative example 3, filler changes to starch, comparative example's 4 binding agents and lubricant change to sodium alginate and magnesium stearate, in comparative example 5, disintegrating agent changes to cross-linking sodium carboxymethyl cellulose, in comparative example 6, filler changes to lactose, binding agent changes to hypromellose, disintegrating agent changes to carboxymethyl starch sodium, lubricant changes to calcium stearate.Experimental data by table 1 and table 2 can be found out, in the identical situation of each composition consumption, no matter be that change has occurred adjuvant type, or adjuvant type does not change but changed the usage ratio of component, the dispersibility of the etoposide tablet preparing and dissolution all significantly reduce.
The test of etoposide tablet stability
Outward appearance, dissolution, content and the disintegration time of the tablet to embodiment 1,2 and comparative example 1-6 have been carried out factors influencing.
(1) hot test: get embodiment 1,2 and comparative example 1-6 sample is laid in culture dish in right amount, the calorstat that is placed in 60 ℃ is placed 10 days, during this 0th, 5,10 days, taking sample determination respectively, measurement result is in Table 3.
(2) high wet test: sample thief is laid in culture dish is in right amount placed 10 days under the condition of 25 ℃ of relative humidity RH90% ± 5%, and during this 0th, 5,10 days, taking sample determination respectively, measurement result is in Table 3.
(3) strong illumination test, sample thief is laid in culture dish in right amount, is placed in light cupboard the condition illumination of 4500Lx ± 500Lx 10 days, and during this 0th, 5,10 days, taking sample determination respectively, measurement result is in Table 3.
Hot and humid and the high light stability inferior of the each embodiment tablet of table 3.
Experimental data by table 3 can be found out, no matter be that change has occurred adjuvant type, or adjuvant type does not change but has changed the usage ratio of component, and the stability of the etoposide tablet preparing (comparative example 1-6) all significantly reduces with respect to embodiment 1,2.
Claims (1)
1. an etoposide tablet, is characterized in that: prescription is by weight:
Wherein etoposide in etoposide clathrate: hydroxypropylβ-cyclodextrin weight ratio is 1:2, in the compositions of lactose and microcrystalline Cellulose, the two part by weight is 7:2.3, in the compositions of polyvinylpolypyrrolidone and carboxymethyl starch sodium, the two part by weight is 3:4.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310092429.3A CN103142522B (en) | 2013-03-21 | 2013-03-21 | Etoposide tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310092429.3A CN103142522B (en) | 2013-03-21 | 2013-03-21 | Etoposide tablet |
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| Publication Number | Publication Date |
|---|---|
| CN103142522A CN103142522A (en) | 2013-06-12 |
| CN103142522B true CN103142522B (en) | 2014-04-30 |
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| CN201310092429.3A Active CN103142522B (en) | 2013-03-21 | 2013-03-21 | Etoposide tablet |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110170058B (en) * | 2019-06-24 | 2022-02-11 | 李建恒 | Abiraterone clathrate compound and preparation method thereof |
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Non-Patent Citations (1)
| Title |
|---|
| 孙鹤文等.中等取代度的羟丙基－β－环糊精对依托泊苷的包埋特性分析.《药物分析杂志》.2011,第31卷(第11期),第2103页右栏第3行至第5行，第2104页第2.4栏和第3.1栏. * |
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