CN100497359C - Novel synthesis process of anti-cancer Sunpla - Google Patents
Novel synthesis process of anti-cancer Sunpla Download PDFInfo
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- CN100497359C CN100497359C CNB2006100106092A CN200610010609A CN100497359C CN 100497359 C CN100497359 C CN 100497359C CN B2006100106092 A CNB2006100106092 A CN B2006100106092A CN 200610010609 A CN200610010609 A CN 200610010609A CN 100497359 C CN100497359 C CN 100497359C
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- platinum
- cancer
- sunpla
- relaxes
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- 238000000034 method Methods 0.000 title claims abstract description 13
- 230000008569 process Effects 0.000 title claims description 10
- 230000001093 anti-cancer Effects 0.000 title claims description 4
- 230000015572 biosynthetic process Effects 0.000 title abstract description 5
- 238000003786 synthesis reaction Methods 0.000 title abstract description 5
- 150000001412 amines Chemical class 0.000 claims abstract description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 118
- 229910052697 platinum Inorganic materials 0.000 claims description 50
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 7
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 5
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 claims description 5
- 229910052709 silver Inorganic materials 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 5
- 229910052753 mercury Inorganic materials 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- 229950006835 eptaplatin Drugs 0.000 abstract description 2
- XJXKGUZINMNEDK-GPJOBVNKSA-L [(4r,5r)-5-(aminomethyl)-2-propan-2-yl-1,3-dioxolan-4-yl]methanamine;platinum(2+);propanedioate Chemical compound [Pt+2].[O-]C(=O)CC([O-])=O.CC(C)C1O[C@H](CN)[C@@H](CN)O1 XJXKGUZINMNEDK-GPJOBVNKSA-L 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000002699 waste material Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 238000001291 vacuum drying Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 229940041181 antineoplastic drug Drugs 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 229940100890 silver compound Drugs 0.000 description 3
- 150000003379 silver compounds Chemical class 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- 101710134784 Agnoprotein Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000001354 calcination Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 190000008236 carboplatin Chemical compound 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000002690 malonic acid derivatives Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010025 steaming Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 101000939135 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 27 Proteins 0.000 description 1
- 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 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 102100029736 Ubiquitin carboxyl-terminal hydrolase 27 Human genes 0.000 description 1
- LPTCUYGPZMAHMM-GPJOBVNKSA-L [(4r,5r)-5-(azanidylmethyl)-2-propan-2-yl-1,3-dioxolan-4-yl]methylazanide;platinum(4+);propanedioate Chemical compound [Pt+4].[O-]C(=O)CC([O-])=O.CC(C)C1O[C@H](C[NH-])[C@@H](C[NH-])O1 LPTCUYGPZMAHMM-GPJOBVNKSA-L 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000005272 metallurgy Methods 0.000 description 1
- 238000005555 metalworking Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 208000012991 uterine carcinoma Diseases 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The related new synthesis technique for Sunpla or Eptaplatin comprises: preparing the complex of M2{Pt[CH2(COO)2]2} with M2PtCl4 and CH2(COOM)2; then reacting with the carrier group of amine(4R, 5R)-4, 5-bi(aminomethyl)-2-isopropyl-1, 3-cyclopentane dioxide. This invention has high yield with short synthesis path and no harmful Ag and Hg to provide high-pure bulk drug.
Description
Technical field
The present invention relates to field of biological pharmacy, particularly relate to the synthesis and preparation process of the easypro platinum (Sunpla) of platinum kind anti-cancer drugs.
Background technology
The platinum (Sunpla) that relaxes claims again according to platinum or platinum in heptan (Eptaplatin), its chemistry is called cis-[(4R, 5R)-4, two (the aminomethyl)-2-sec.-propyls-1 of 5-, 3-dioxolanes alkane] (malonate) close platinum (II), structural formula is as follows, and it is a kind of novel platinum kind anti-cancer drugs of Korea S's SunkyongIndustries life science center exploitation, goes on the market in Korea S's approval in 1999.Principal indication be cancer of the stomach, small cell lung cancer, incidence cancer, colorectal carcinoma, uterus carcinoma etc. [new drug introduction---the platinum antineoplastic medicine of new generation platinum that relaxes. world's clinical medicine, 2003,24 (6), 379; Liu Wei equality. the platinum metal complex that the treatment cancer is used. pharmacy progress, 2001,25 (1), 27-30; The Peng Sixun chief editor. pharmacy progress, 2003,2,161～187].The clinical efficacy of platinum is remarkable owing to relax, the listing of Sunkyong Industries forward US and European application at present, and China also has research institution carrying out clinical study.
Platinum relaxes
At present, synthetic [Jin Daqi, the conspicuous grade of Kingcon (bright metal working is Co., Ltd. already), the CN 1038590C of the easypro platinum of patent report; Xu Mingbo, Zhang Baoge etc. (Beijing Shuanglu Pharmaceutical Co., Ltd.), CN 1629171A] all quote classical synthetic method [the Ernest Wong of platinum kind anti-cancer drugs such as cis-platinum, carboplatin, oxaliplatin etc., Christen M G.Current Status of Platinum-basedAntitumor Drugs.Chem.Rev., 1999,99:2451-2466], promptly with K
2PtCl
4Be starting raw material, realize by following three steps:
(1) adds KI, change into K
2PtI
4, with carrier group amine (4R, 5R)-4, two (the aminomethyl)-2-sec.-propyls-1 of 5-, corresponding cis-[Pt (II) A is prepared in the reaction of 3-dioxolanes
2I
2] intermediate (A
2=(4R, 5R)-4, two (the aminomethyl)-2-sec.-propyls-1 of 5-, 3-dioxolanes).
(2) cis-[Pt (II) A
2I
2] intermediate and AgNO
3Or Ag
2SO
4Or Ag
2The O reaction, filtering separation AgI precipitation obtains cis-[Pt (II) A
2(H
2O)
2]
2+
(3) potassium or the sodium salt with the leavings group propanedioic acid reacts, and makes the easypro platinum of target compound.Or intermediate cis-[Pt (II) A
2I
2] directly with the silver salt reaction of propanedioic acid, filtering separation AgI precipitation, mother liquor concentrates and obtains easypro platinum.
The synthetic method of report such as Wu Yuxia is with Hg
2(NO
3)
2[Wu Yuxia etc., inorganic chemistry, 2004,20 (2), 215-218] substitutes AgNO
3Or Ag
2SO
4Or Ag
2O and cis-[Pt (II) A
2I
2] reaction, filtering separation Hg
2I
2Precipitation makes cis-[Pt (II) A
2(H
2O)
2]
2+After, (3) the step reaction by patent report obtains the platinum that relaxes again.
There is following shortcoming and defect in the synthetic method of the easypro platinum that existing patent and document adopt: the first, owing to used silver compound in synthetic, can introduce silver-colored impurity in the easypro platinum of final product, and influence the quality of product.Ag-containing compound injection has high toxicity to human body, thus American Pharmacopeia (USP27) and European Pharmacopoeia (EP4) silver content in the platinum kind anti-cancer drugs is limited, as carboplatin Ag＜15ppm; Oxaliplatin Ag＜5ppm.And mercury is bigger to human toxicity, and it is worthless therefore adopting the alternative silver compound of compound of mercury in synthetic.The second, cis-[Pt (II) A
2I
2] intermediate and the reaction of corresponding silver compound not exclusively, the unreacted platinic compound of 10-20% enters in the AgI precipitation.The separation of platiniferous AgI waste residue and recovery are the difficult problems in the metallurgy always, need wet method and pyrogenic process coupling to use the recovery that just can reach Pt, Ag.Because treating processes is long, causes dispersion and the loss of Pt, with K
2PtCl
4For starting raw material calculates, the loss of metal platinum reaches 5%, has increased the production cost of easypro platinum greatly.
Summary of the invention
The object of the invention provides a kind of novel process of the synthetic platinum that relaxes, this process yield height, and production process is not introduced Ag-containing compound, can improve the quality of products, and solves the metallurgical difficult problem of the separation and the recovery of platiniferous AgI waste residue simultaneously.
Synthetic novel process of relaxing platinum of the present invention is: earlier tetrachloro is closed inferior platinate M
2PtCl
4With malonate CH
2(COOM)
2Reaction generates a kind of new title complex-two (malonate) and closes platinum (II) hydrochlorate M
2{ Pt[CH
2(COO)
2]
2, then with carrier group amine (4R, 5R)-4, two (the aminomethyl)-2-sec.-propyls-1 of 5-, 3-dioxolanes react the target compound platinum that relaxes.Its chemical reaction and route are:
Platinum relaxes
The novel process of the synthetic platinum that relaxes of the present invention; have that synthetic route is short, productive rate is high, do not introduce harmful heavy metal Ag and Hg, can improve the quality of products, the platiniferous waste recovery is simple and the little advantage of loss of platinum; be produced on a large scale; the method that obviously is better than existing patent and document provides highly purified bulk drug for producing the platinum preparation that relaxes.
Embodiment
Embodiment 1
(1), two (malonates) close the preparation of the sour potassium of platinum (II)
Get 10g (24mmol) K
2PtCl
4, be dissolved in the water of 100ml, add 35g (192mmol) CH
2(COOK)
2And 4.9g (48mmol) CH
2(COOH)
2, 75 ℃ of reactions 8 hours, the xanchromatic crystallization was separated out in cooling, filtered and collected, and 65 ℃ of following vacuum-dryings 4 hours, obtained 9.63g K after water, the washing with alcohol
2{ Pt[CH
2(COO)
2]
22H
2O, productive rate 85%.
The feature structure parameter is:＜1 〉. ultimate analysis C 14.11%; H 1.57%; Pt 38.2%, with theoretical value C 14.04%; H1.560%; Pt 38.0% unanimity.<2>.FAB
+-MS?m/e＝400(Pt[CH
2(COO)
2]
2+，45％)。＜3〉.IR (cm
-1, the KBr compressing tablet) and 3572-3495 (s, vO-H, H
2O) 2861 (w, vCH2), 1635[vs vas (COO)], 1370[svs (COO)].These parameters meet K
2{ Pt[CH
2(COO)
2]
22H
2The chemical structure of O.
(2), easypro platinum is synthetic
Get 4g (7.8mmol) K
2{ Pt[CH
2(COO)
2]
22H
2O is dissolved in the water of 20ml, under agitation slowly drips (the 4R of 1.6g (9.2mmol), 5R)-4, two (the aminomethyl)-2-sec.-propyls-1 of 5-, behind the 3-dioxolanes, heating reflux reaction 12 hours, cooling, separate out the crystallization of off-white color, filter to collect, after water, the washing with alcohol 65 ℃ of following vacuum-dryings 4 hours, obtain the easypro platinum of 2.6g, productive rate 70%.
(3), the purification of easypro platinum
Get the easypro platinum crude product of 2g, be dissolved in the boiling water of 40ml, take advantage of heat to filter fast, filtrate is cooled to 5 ℃, separate out the crystallization of white, filter and collect, 65 ℃ of following vacuum-dryings 4 hours, obtain the easypro platinum elaboration of 1.8g after water, the washing with alcohol, productive rate 90%, it is 99.2% that purity is analyzed through HPLC, and silver content is determined as＜1ppm through AAS, specific rotatory power-46 °.
The feature structure parameter is:＜1 〉. ultimate analysis C 28.1%; H 4.17%; N 6.02%; Pt 41.5%, and is consistent with theoretical value.<2>.FAB
+-MS?m/e＝472(M
+，100％)。＜3〉.IR (cm
-1, the KBr compressing tablet) and
1(DMSO is ppm) with the unanimity of bibliographical information [J.Med.Chem., 1994,37,1471-1485] for HNMR.These parameters meet the chemical structure of the platinum that relaxes.
(4), the recovery of platiniferous waste material
The platiniferous waste liquid of the first step and the reaction of second step is concentrated, after 75 ℃ ethanol is removed in decompression steaming slide down, transfer in the beaker, be heated to and boil, regulate PH with ammoniacal liquor 11, drip hydrazine hydrate reduction platinum to reaction solution colourless till, continued reacting by heating 40 minutes, cooling is filtered and is collected platinum in filter paper, wash the back with water 850 ℃ of following calcinations 4 hours, obtaining metal platinum, is 99.95% through emmission spectrometric analysis purity, and the loss of platinum is (with K
2PtCl
4The charging capacity meter) less than 0.25%.
Embodiment 2
(1), two (malonates) close the preparation of the sour sodium of platinum (II)
Get 9.2g (24mmol) Na
2PtCl
4, be dissolved in the water of 100ml, add 28.4g (192mmol) CH
2(COONa)
2And 4.9g (48mmol) CH
2(COOH)
2, 75 ℃ of reactions 8 hours, flaxen crystallization was separated out in cooling, filtered and collected, and 65 ℃ of following vacuum-dryings 4 hours, obtained 7.5g Na after water, the washing with alcohol
2{ Pt[CH
2(COO)
2]
2H
2O, productive rate 75%, Pt42.8%.
(2), easypro platinum is synthetic
Get 3.55g (7.8mmol) Na
2{ Pt[CH
2(COO)
2]
22H
2O is dissolved in the water of 20ml, under agitation slowly drips (the 4R of 1.6g (9.2mmol), 5R)-4, two (the aminomethyl)-2-sec.-propyls-1 of 5-, behind the 3-dioxolanes, heating reflux reaction 12 hours, cooling, separate out the crystallization of off-white color, filter to collect, after water, the washing with alcohol 65 ℃ of following vacuum-dryings 4 hours, obtain the easypro platinum of 2.34g, productive rate 65%.
(3), the purification of easypro platinum
Get the easypro platinum crude product of 2g, be dissolved in the boiling water of 40ml, take advantage of heat to filter fast, filtrate is cooled to 5 ℃, separate out the crystallization of white, filter and collect, 65 ℃ of following vacuum-dryings 4 hours, obtain the easypro platinum elaboration of 1.7g after water, the washing with alcohol, productive rate 86%, it is 99.4% that purity is analyzed through HPLC, and silver content is determined as＜1ppm through AAS, specific rotatory power-44 °.
(4), the recovery of platiniferous waste material
The platiniferous waste liquid of the first step and the reaction of second step is concentrated, after 75 ℃ ethanol is removed in decompression steaming slide down, transfer in the beaker, be heated to and boil, regulate PH with ammoniacal liquor 11, drip hydrazine hydrate reduction platinum to reaction solution colourless till, continued reacting by heating 30 minutes, cooling is filtered and is collected platinum in filter paper, wash the back with water 800 ℃ of following calcinations 4 hours, obtaining metal platinum, is 99.99% through emmission spectrometric analysis purity, and the loss of platinum is (with K
2PtCl
4The charging capacity meter) less than 0.3%.
Claims (2)
1. the novel process of a synthetic anti-cancer Sunpla is characterized in that containing the following step: earlier tetrachloro is closed inferior platinate M
2PtCl
4With malonate CH
2(COOM)
2Reaction generates a kind of new title complex-two (malonate) and closes platinum (II) hydrochlorate M
2{ Pt[CH
2(COO)
2]
2, then with carrier group amine (4R, 5R)-4, two (the aminomethyl)-2-sec.-propyls-1 of 5-, 3-dioxolanes react the target compound platinum that relaxes, its chemical reaction and route are:
2. the novel process of synthetic anti-cancer Sunpla according to claim 1 is characterized in that using down the novel complexes of array structure to be intermediate, wherein M=Na
+, K
+, Li
+Or Cs
+
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100106092A CN100497359C (en) | 2006-01-06 | 2006-01-06 | Novel synthesis process of anti-cancer Sunpla |
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|---|---|---|---|
| CNB2006100106092A CN100497359C (en) | 2006-01-06 | 2006-01-06 | Novel synthesis process of anti-cancer Sunpla |
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| Publication Number | Publication Date |
|---|---|
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| CN100497359C true CN100497359C (en) | 2009-06-10 |
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|---|---|---|---|
| CNB2006100106092A Expired - Fee Related CN100497359C (en) | 2006-01-06 | 2006-01-06 | Novel synthesis process of anti-cancer Sunpla |
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Families Citing this family (1)
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| CN105218589A (en) * | 2015-10-10 | 2016-01-06 | 山东铂源药业有限公司 | A kind of synthetic method of oxaliplatin |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1038590C (en) * | 1991-03-23 | 1998-06-03 | 鲜京工业株式会社 | The preparation method of platinum complex |
| CN1152036C (en) * | 2001-09-14 | 2004-06-02 | 南京大学 | A method for preparing platinum(Ⅱ) complexes |
| CN1569863A (en) * | 2004-04-28 | 2005-01-26 | 南京科源医药技术有限公司 | Method for preparing platinum(II) metal complex eptaplatin |
| CN1629171A (en) * | 2004-10-22 | 2005-06-22 | 北京双鹭药业股份有限公司 | Novel sunplatinum preparation and its preparation process |
-
2006
- 2006-01-06 CN CNB2006100106092A patent/CN100497359C/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1038590C (en) * | 1991-03-23 | 1998-06-03 | 鲜京工业株式会社 | The preparation method of platinum complex |
| CN1152036C (en) * | 2001-09-14 | 2004-06-02 | 南京大学 | A method for preparing platinum(Ⅱ) complexes |
| CN1569863A (en) * | 2004-04-28 | 2005-01-26 | 南京科源医药技术有限公司 | Method for preparing platinum(II) metal complex eptaplatin |
| CN1629171A (en) * | 2004-10-22 | 2005-06-22 | 北京双鹭药业股份有限公司 | Novel sunplatinum preparation and its preparation process |
Non-Patent Citations (4)
| Title |
|---|
| 制备抗肿瘤药物庚铂的新方法. 吴玉霞等.无机化学学报，第20卷第2期. 2004 |
| 制备抗肿瘤药物庚铂的新方法. 吴玉霞等.无机化学学报，第20卷第2期. 2004 * |
| 铂类抗癌药物展望. 刘伟平等.贵金属，第26卷第1期. 2005 |
| 铂类抗癌药物展望. 刘伟平等.贵金属，第26卷第1期. 2005 * |
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| Publication number | Publication date |
|---|---|
| CN1803813A (en) | 2006-07-19 |
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