CN101255157A - Crystal system of chlorhydric acid palonosetron and preparation method thereof - Google Patents
Crystal system of chlorhydric acid palonosetron and preparation method thereof Download PDFInfo
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- CN101255157A CN101255157A CNA2008100595276A CN200810059527A CN101255157A CN 101255157 A CN101255157 A CN 101255157A CN A2008100595276 A CNA2008100595276 A CN A2008100595276A CN 200810059527 A CN200810059527 A CN 200810059527A CN 101255157 A CN101255157 A CN 101255157A
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Abstract
The invention relates to two novel crystal forms of palonosetron hydrochloride that are A and B crystal forms. The A and B crystal forms have characteristic diffraction peaks when x-ray diffraction is used on the powder under Cu-K alpha radiation conditional (lamed=1. 54059) and the bragg 2theta angle between 0 and 50 degree C. The A crystal form has aendothermic peak near 320. 678 degree C, and the B crystal form has a endothermic peak near 320. 68 degree C after performed differential thermal analysis. Further the invention also relates to a process for preparing the crystal forms and pharmaceutical compositions containing the crystal forms.
Description
Technical field
The present invention relates to crystal formation, its preparation method of RS 25259-197 and contain the pharmaceutical composition of these crystal formations.
Background of invention
RS 25259-197 (Palonosetron hydrochloride, trade(brand)name Aloxi) is the selectivity 5-HT3 receptor antagonist of developing by Switzerland Helsinn company, chemistry is by name: (3aS)-2-[(3S)-1-azabicyclo [2.2.2] octyl]-2,3,3a, 4,5,6-six hydrogen-1-oxo-1H-phenylhydrazine [de] isoquinoline hydrochloride, its molecular structural formula is as follows.On July 25th, 2003, this product obtained FDA (FDA) approval, was used for the treatment of moderate or highly caused the acute and tardy property nausea and vomiting that vomitting property chemotherapy causes.
RS 25259-197 is the 4th granted 5-HT
3Receptor antagonist.A key property of Palonosetron is a long half time, has 40 hours approximately, and other 5-HT
3The transformation period of receptor antagonist has only a few hours.And Palonosetron can optionally be attached to 5-HT
3On the acceptor, have stronger affinity, with the avidity of acceptor almost be other 5-HT
3100 times of antagonist.
Report that the earliest RS 25259-197 synthetic document is a U.S. Pat 5202333, this patent disclosure the application of medicinal compositions in vomiting that the treatment chemicotherapy causes, pain, gastrointestinal disturbance etc. of the preparation method of RS 25259-197 and hydrochloric Palonosetron.A kind of synthesis technique of new RS 25259-197 is disclosed in U.S. Pat 5510486 in addition.But the synthetic also reference Synthesis of relevant RS 25259-197,1996,7:816-818.
But above-mentioned these documents are the crystal formation and the preparation method of not mentioned RS 25259-197 all, the spectral response curve of more not mentioned relevant crystal formation.
Summary of the invention
The purpose of this invention is to provide a kind of new crystal, its preparation method of RS 25259-197 and contain the pharmaceutical composition of these crystal formations.
The invention discloses two new crystal of RS 25259-197, below be referred to as A type and Type B.Described A crystal formation use Cu-K α radiation condition (λ=
), the powder x-ray diffraction when 2 θ angles are 0-50 ° in Prague has following characteristic peak: (d) is expressed as with spacing
Described B crystal formation use Cu-K α radiation condition (λ=
), the powder x-ray diffraction when 2 θ angles are 0-50 ° in Prague has following characteristic peak: (d) is expressed as with spacing
Described Palonosetron A or B crystal formation are surveyed infrared absorption spectrum with the KCl pressed disc method, and its absorption peak is similar.Described A type is at about 3025cm
-12924cm
-12861cm
-12508cm
-12456cm
-11647cm
-11591cm
-11408cm
-1769cm
-1There is absorption peak at the place.Described Type B is at about 3023cm
-12924cm
-12861cm
-12453cm
-11647cm
-11590cm
-11408cm
-1768cm
-1There is absorption peak at the place.
Adopt Perkin Elmer Diamond Differential Scanning CalorimeterAutosample equipment that A and B crystal formation are carried out differential thermal analysis, temperature range is 50 ℃-350 ℃, rate of heating is 10 ℃/minute, the result shows that the DSC collection of illustrative plates of A and B crystal formation is similar, the A crystal formation has endotherm(ic)peak near 320.678 ℃, the B crystal formation has endotherm(ic)peak near 320.68 ℃.
The invention also discloses the A crystal formation of preparation RS 25259-197 and the method for B crystal formation, these two kinds of methods are simple, are suitable for suitability for industrialized production, and generate crystal formation yield height.
The A crystal formation generally can prepare by the following method:
(1) RS 25259-197 is placed the Virahol of 10-30 times of Palonosetron bulking value and the mixed solvent of water;
(2) after the heating for dissolving, reheat evaporates the solvent volume about about 10%-35% or adds the Virahol of 5-10 times of Palonosetron bulking value again;
(3) cooling, crystallization filters, 80-90 ℃ vacuum-drying 4-6 hour, collect crystallisate.
As a kind of alternative plan, RS 25259-197 can be placed the Virahol of 10-30 times of RS 25259-197 bulking value (1 bulking value is defined as by every 1g RS 25259-197 and adds the 1ml solvent) and the mixed solvent of water, preferred 15-20 times of RS 25259-197 bulking value.The water yield is preferably the 1-8% of mixed solvent volume, is preferably 2-6%, more preferably about 4-5%.After heating made RS 25259-197 dissolving, the solvent volume about the about 10%-35% of heating evaporation or add the Virahol of 5-10 times of RS 25259-197 bulking value again was cooled to about 0-10 ℃, crystallization 2-5 hour, filter, 80-90 ℃ vacuum-drying 4-6 hour, collect crystallisate.
The B crystal formation generally can prepare by the following method:
(1) RS 25259-197 is placed the ethanol or the dimethyl formamide (DMF) of 30-60 times of RS 25259-197 bulking value;
(2) after heating makes it dissolving, cooling;
(3) stirring and crystallizing is filtered, 80-90 ℃ vacuum-drying 4-6 hour, collect crystallisate.
As a kind of alternative plan, RS 25259-197 can be placed the ethanol or the dimethyl formamide (DMF) of 30-60 times of RS 25259-197 bulking value (1 bulking value is defined as by every 1g RS 25259-197 and adds the 1ml solvent), preferred 40-50 times of RS 25259-197 bulking value.Heating is cooled to about 0-10 ℃ after making it dissolving, stirring and crystallizing 2-5 hour, filter, 80-90 ℃ vacuum-drying 4-6 hour, collect crystallisate.
Another object of the present invention provides a kind of pharmaceutical composition, A type or Type B RS 25259-197 crystallisate and at least a pharmaceutically acceptable carrier that it contains significant quantity can be used for treating moderate or highly cause the acute and tardy property nausea and vomiting that vomitting property chemotherapy causes.
RS 25259-197 obtains the approval of U.S. FDA in July, 2003, be used for preventing moderate and highly cause vomiting chemotherapy of tumors acute nausea and vomiting initial and that repeat a treatment and tardy property nausea and vomiting symptom, and to be first individually dosedly be used for treating the 5-HT that moderate causes vomiting chemotherapy of tumors patient's tardy property symptoms of emesis by what FDA ratified
3Receptor antagonist.
But the pharmaceutical dosage form of above-mentioned approval is an injection liquid, and specification is 0.25mg/5ml.This means that patient must be in hospital undergoing treatment, and the injection meeting brings misery and inconvenience to patient, especially unfavorable for the patient who produces tardy property nausea and vomiting symptom after the chemotherapy.And oral administration can make things convenient for patient's administration, is beneficial to treatment.
RS 25259-197 A type disclosed by the invention and Type B crystallization have definite structure, and its crystallized form is highly stable, and tap density is good, can not transform automatically between these two crystal formations.Sealing was preserved more than half a year in 40 ℃ of accelerated tests and 50% humidity environment, and crystal formation is constant substantially, and content does not reduce, can be under lucifuge, cool place and drying conditions prolonged preservation, be suitable for preparing oral administered dosage form.Consider the absorption problem of oral administration, active ingredient hydrochloric acid Palonosetron A type and Type B crystalline dosage should be more than 0.25mg.
RS 25259-197 A type or the Type B crystalline pharmaceutical composition of containing disclosed in this invention, can be that tablet (as enteric coated tablet, coating tablet, film coated tablet, coated tablet, medicinal extract sheet, dispersible tablet, cut sheet etc.), hard capsule, soft capsule (capsule and pill), enteric coated capsule, sustained-release and controlled release formulation, slow releasing tablet, sustained release coating and other are any be fit to oral formulation for it.The carrier that the pharmacy that is fit to can go up acceptance can be starch, Mierocrystalline cellulose, talcum, sugar (lactose, glucose, sucrose etc.), dextrin, lime carbonate, magnesium oxide, N.F,USP MANNITOL, poly-methyl acrylate, Repone K, sodium-chlor, sorbyl alcohol, secondary calcium phosphate, croscarmellose sodium, Natvosol, gelatin, hydroxypropylcellulose, sodium alginate, carboxymethyl cellulose, carboxyethyl cellulose, colloid silica, Magnesium Stearate, hydrogenated vegetable oil, polyoxyethylene glycol, palmitostearate, citric acid, wherein one or more such as neusilin.In final pharmaceutical composition, the content of RS 25259-197 is 0.00001%-5%, preferred 0.01%-1.5%.
As a kind of selection, embodiment 10 discloses a kind of tablet, and every medicament RS 25259-197 A type crystalline content is 1%, and carboxymethyl cellulose level is 70%, and palmitostearate is 15%, and dextrin content is 10%, and neusilin content is 4%.
Embodiment 11 discloses a kind of capsule, and wherein RS 25259-197 Type B crystalline content is 1.5%, and lactose hydrous content is 10%, and the microcrystalline cellulose cellulose content is 75%, and croscarmellose sodium content is 8.5%, and Magnesium Stearate content is 5%.
Description of drawings
Accompanying drawing 1 is the powder x-ray diffraction spectrogram of RS 25259-197 A crystal formation
Accompanying drawing 2 is powder x-ray diffraction spectrograms of RS 25259-197 B crystal formation
Accompanying drawing 3 is infrared absorption patterns of RS 25259-197 A crystal formation
Accompanying drawing 4 is infrared absorption patterns of RS 25259-197 B crystal formation
Accompanying drawing 5 is DSC collection of illustrative plates of RS 25259-197 A crystal formation
Accompanying drawing 6 is DSC collection of illustrative plates of RS 25259-197 B crystal formation
Embodiment
The preparation one of embodiment 1 RS 25259-197 A crystal formation
Get RS 25259-197 5g, add 115ml Virahol and 4ml water, heating makes it dissolving.After treating the whole dissolvings of solid, continue heating, after air distillation goes out 36ml liquid, be cooled to 0 ℃, stir, crystallization 2 hours, after-filtration is separated out in crystallization, in 80 ℃ of vacuum-dryings 4 hours, gets the pure product 4.4g of crystallisate, and it is 99.7% that HPLC detects purity.
The preparation two of embodiment 2 RS 25259-197 A crystal formations
Get RS 25259-197 8g, add 124ml Virahol and 6.4ml water, heating makes it dissolving.After treating that solid all dissolves, add Virahol 54ml, be cooled to 0 ℃, stir, crystallization 4 hours, after-filtration is separated out in crystallization, in 80 ℃ of vacuum-dryings 4 hours, gets the pure product 7.56g of crystallisate, and it is 99.6% that HPLC detects purity.
The preparation one of embodiment 3 RS 25259-197 B crystal formations
Get RS 25259-197 5g, add 200ml ethanol, after heating made the solid dissolving, cooling 10 ℃ of stirring and crystallizing 2 hours, was filtered, in 80 ℃ of vacuum-dryings 4 hours, pure product 4.3 grams of crystallisate, it is 99.2% that HPLC detects purity.
The preparation two of embodiment 4 RS 25259-197 B crystal formations
Get RS 25259-197 5g, add 200ml dimethyl formamide (DMF), after heating made the solid dissolving, cooling 5 ℃ of stirring and crystallizing 4 hours, was filtered, in 80 ℃ of vacuum-dryings 4 hours, pure product 4.5 grams of crystallisate, it is 99.3% that HPLC detects purity.
Embodiment 5 RS 25259-197 A crystal formations are measured
The crystallisate powder of getting embodiment 1 preparation carries out X ray diffracting spectrum to be measured, described A crystal formation use Cu-K α radiation condition (λ=
), the x-ray diffractogram of powder when 2 θ angles are 0-50 ° in Prague spectrum data are as shown in table 1, wherein 2Tetha is 2 θ angles, d is a spacing, I/I
0Represent relative intensity, the per-cent that accounts for area under the intense line with area under a certain spectral line is represented.Characteristic peak as shown in Figure 1, its characteristic peak is expressed as with spacing d (round up and get hundredths)
Characteristic peak herein is defined as I/I
0>20%.
Table 1A crystal formation x-ray diffractogram of powder spectrum data
2-Theta | d | I/I 0(%) |
7.054 | 12.5219 | 5.2 |
10.413 | 8.4884 | 8.8 |
12.081 | 7.3202 | 33.5 |
12.323 | 7.1770 | 3.9 |
13.764 | 6.4287 | 56.8 |
14.134 | 6.2610 | 42.1 |
14.444 | 6.1275 | 29.3 |
15.765 | 5.6167 | 96.0 |
16.921 | 5.2356 | 27.7 |
17.225 | 5.1438 | 18.5 |
18.454 | 4.8040 | 68.8 |
18.693 | 4.7429 | 19.7 |
19.663 | 4.5112 | 100.0 |
19.983 | 4.4398 | 70.1 |
20.262 | 4.3792 | 7.1 |
20.932 | 4.2404 | 21.9 |
21.269 | 4.1740 | 3.6 |
22.383 | 3.9688 | 1.2 |
22.995 | 3.8646 | 20.5 |
23.271 | 3.8194 | 57.4 |
23.465 | 3.7882 | 34.7 |
23.735 | 3.7456 | 30.3 |
24.080 | 3.6927 | 25.4 |
24.392 | 3.6462 | 28.7 |
24.791 | 3.5885 | 14.8 |
25.376 | 3.5070 | 16.0 |
26.053 | 3.4174 | 1.3 |
26.342 | 3.3806 | 5.0 |
26.713 | 3.3345 | 13.0 |
26.784 | 3.3258 | 13.0 |
27.731 | 3.2143 | 25.1 |
29.163 | 3.0597 | 7.9 |
29.359 | 3.0397 | 8.8 |
29.760 | 2.9996 | 2.4 |
30.194 | 2.9575 | 9.7 |
30.934 | 2.8884 | 0.4 |
31.217 | 2.8629 | 2.7 |
31.402 | 2.8465 | 10.8 |
31.595 | 2.8295 | 17.8 |
31.839 | 2.8084 | 14.8 |
31.900 | 2.8032 | 12.3 |
32.081 | 2.7877 | 14.0 |
32.247 | 2.7738 | 27.1 |
32.851 | 2.7241 | 4.0 |
33.621 | 2.6635 | 11.6 |
33.837 | 2.6469 | 10.6 |
34.226 | 2.6178 | 6.2 |
34.765 | 2.5784 | 2.3 |
35.177 | 2.5492 | 4.3 |
35.827 | 2.5044 | 3.3 |
35.924 | 2.4979 | 12.2 |
36.087 | 2.4869 | 3.5 |
36.667 | 2.4489 | 5.1 |
36.837 | 2.4380 | 7.4 |
36.923 | 2.4325 | 8.9 |
37.230 | 2.4131 | 3.8 |
37.513 | 2.3956 | 4.1 |
37.848 | 2.3752 | 4.5 |
38.044 | 2.3634 | 5.1 |
38.763 | 2.3212 | 9.9 |
38.915 | 2.3124 | 12.9 |
39.096 | 2.3021 | 7.0 |
39.890 | 2.2582 | 5.9 |
40.108 | 2.2464 | 5.3 |
41.455 | 2.1765 | 2.8 |
42.435 | 2.1284 | 7.0 |
42.607 | 2.1202 | 11.1 |
43.320 | 2.0870 | 7.2 |
44.267 | 2.0445 | 5.4 |
44.524 | 2.0333 | 7.9 |
45.058 | 2.0104 | 7.5 |
46.226 | 1.9623 | 14.0 |
46.481 | 1.9521 | 13.3 |
48.267 | 1.8840 | 4.9 |
48.573 | 1.8728 | 7.0 |
48.718 | 1.8676 | 3.9 |
49.240 | 1.8490 | 4.2 |
Embodiment 6 RS 25259-197 B crystal formations are measured
The crystallisate powder of getting embodiment 4 preparation carries out X ray diffracting spectrum to be measured, described B crystal formation use Cu-K α radiation condition (λ=
), the x-ray diffractogram of powder when 2 θ angles are 0-50 ° in Prague spectrum data are as shown in table 2,2-Theta is 2 θ angles, d is a spacing, I/I
0Represent relative intensity, the per-cent that accounts for area under the intense line with area under a certain spectral line is represented.Characteristic peak as shown in Figure 2, its characteristic peak is expressed as with spacing d (round up and get hundredths)
Characteristic peak herein is defined as I/I
0>20%.
Table 2B crystal formation x-ray diffractogram of powder spectrum data
2-Theta | d | I/I 0(%) |
7.062 | 12.5070 | 11.7 |
9.922 | 8.9078 | 11.3 |
11.357 | 7.7849 | 6.4 |
12.982 | 6.8137 | 67.4 |
13.699 | 6.4587 | 21.2 |
14.162 | 6.2488 | 66.7 |
15.381 | 5.7561 | 27.5 |
16.138 | 5.4878 | 25.3 |
16.342 | 5.4197 | 8.2 |
17.537 | 5.0529 | 22.7 |
18.438 | 4.8082 | 63.0 |
19.941 | 4.4491 | 100.0 |
21.320 | 4.1642 | 4.5 |
21.921 | 4.0514 | 9.4 |
22.119 | 4.0156 | 16.6 |
23.182 | 3.8337 | 36.1 |
23.560 | 3.7732 | 9.2 |
24.399 | 3.6452 | 25.3 |
24.838 | 3.5817 | 35.1 |
25.100 | 3.5450 | 30.9 |
26.198 | 3.3988 | 4.4 |
27.561 | 3.2338 | 23.2 |
28.919 | 3.0849 | 13.5 |
29.680 | 3.0076 | 6.6 |
31.500 | 2.8378 | 17.3 |
31.641 | 2.8254 | 24.4 |
31.964 | 2.7977 | 5.4 |
32.402 | 2.7608 | 12.8 |
32.618 | 2.7431 | 6.7 |
33.703 | 2.6572 | 3.4 |
34.141 | 2.6241 | 3.4 |
34.542 | 2.5945 | 4.8 |
35.499 | 2.5267 | 4.6 |
35.903 | 2.4992 | 5.1 |
37.280 | 2.4101 | 4.4 |
37.620 | 2.3890 | 3.6 |
37.899 | 2.3721 | 3.7 |
38.762 | 2.3212 | 9.0 |
39.700 | 2.2685 | 3.7 |
40.638 | 2.2183 | 5.9 |
42.321 | 2.1339 | 3.4 |
43.421 | 2.0824 | 5.5 |
44.899 | 2.0172 | 11.7 |
45.121 | 2.0078 | 11.7 |
45.880 | 1.9763 | 9.5 |
46.118 | 1.9666 | 14.6 |
47.743 | 1.9034 | 3.2 |
Embodiment 7A crystal formation infrared absorption spectrum
With the KCl pressed disc method Palonosetron A crystal formation is measured infrared absorption spectrum, the A crystal formation is at about 3025cm
-12924cm
-12861cm
-12508cm
-12456cm
-11647cm
-11591cm
-11408cm
-1769cm
-1There is absorption peak at the place.Accompanying drawing 3 is the infrared absorption pattern of A crystal formation.
Embodiment 8B crystal formation infrared absorption spectrum
With the KCl pressed disc method Palonosetron B crystal formation is measured infrared absorption spectrum, the B crystal formation at described approximately Type B at about 3023cm
-12924cm
-12861cm
-12453cm
-11647cm
-11590cm
-11408cm
-1768cm
-1There is absorption peak at the place.Accompanying drawing 4 is the infrared absorption pattern of B crystal formation.
Embodiment 9 differential thermal analysis (DSC)
Adopt Perkin Elmer Diamond Differential Scanning CalorimeterAutosample equipment that A or B crystal formation are carried out calorimetric analysis, temperature range is 50 ℃-350 ℃, rate of heating is 10 ℃/minute, the result shows that the DSC collection of illustrative plates of A and B crystal formation is similar, the A crystal formation has endotherm(ic)peak near 320.678 ℃, the B crystal formation has endotherm(ic)peak near 320.68 ℃.。Accompanying drawing 5 is the DSC collection of illustrative plates of A crystal formation, and accompanying drawing 6 is the DSC collection of illustrative plates of B crystal formation.
The preparation of embodiment 10 RS 25259-197 A type crystallization tablets
A kind of tablet, wherein RS 25259-197 A type crystalline content is 1%, and carboxymethyl cellulose level is 70%, and palmitostearate is 15%, and dextrin content is 10%, neusilin content is 4%.Every tablet of medicament contains the about 0.5mg of RS 25259-197 A type crystallization.
The capsular preparation of embodiment 11 RS 25259-197 Type B crystallizations
A kind of capsule, wherein RS 25259-197 Type B crystalline content is 1.5%, and lactose hydrous content is 10%, and the microcrystalline cellulose cellulose content is 75%, and croscarmellose sodium content is 8.5%, Magnesium Stearate content is 5%.The hydrochloric Palonosetron Type B of every capsules crystallization 1mg.
Claims (10)
2, the A crystal formation of RS 25259-197 according to claim 1 is characterized in that: described A crystal formation infrared absorption spectrum is at about 3025cm
-12924cm
-12861cm
-12508cm
-12456cm
-11647cm
-11591cm
-11408cm
-1769cm
-1There is absorption peak at the place.
3, the A crystal formation of RS 25259-197 according to claim 1 is characterized in that: the differential thermal analysis collection of illustrative plates (DSC) of described A crystal formation has been located endotherm(ic)peak at 320.678 ℃.
4, the method for preparation RS 25259-197 A crystal formation as claimed in claim 1 comprises the steps:
(1) RS 25259-197 is placed the Virahol of 10-30 times of Palonosetron bulking value and the mixed solvent of water;
(2) after the heating for dissolving, reheat evaporates the solvent volume about about 10%-35% or adds the Virahol of 5-10 times of Palonosetron bulking value again;
(3) cooling, crystallization filters, 80-90 ℃ vacuum-drying 4-6 hour, collect crystallisate.
6, the B crystal formation of RS 25259-197 according to claim 5 is characterized in that: described B crystal formation infrared absorption spectrum at described Type B at about 3023cm
-12924cm
-12861cm
-12453cm
-11647cm
-11590cm
-11408cm
-1768cm
-1There is absorption peak at the place.
7, the B crystal formation of RS 25259-197 according to claim 5 is characterized in that: the differential thermal analysis collection of illustrative plates (DSC) of described B crystal formation has been located endotherm(ic)peak at 320.68 ℃.
8, the method for the B crystal formation of preparation RS 25259-197 as claimed in claim 5 comprises the steps:
(1) RS 25259-197 is placed the ethanol or the dimethyl formamide (DMF) of 30-60 times of RS 25259-197 bulking value;
(2) after heating makes it dissolving, cooling;
(3) crystallization filters, 80-90 ℃ vacuum-drying 4-6 hour, collect crystallisate.
9, a kind of pharmaceutical composition, it contains A type or the Type B RS 25259-197 crystallisate and at least a pharmaceutically acceptable carrier of significant quantity.
10, pharmaceutical composition according to claim 9 is characterized in that: to be that tablet, hard capsule, soft capsule, enteric coated capsule, sustained-release and controlled release formulation, slow releasing tablet, sustained release coating and other are any be fit to oral formulation to the formulation of described pharmaceutical composition.
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009087643A1 (en) * | 2008-01-11 | 2009-07-16 | Natco Pharma Limited | Novel crystalline forms of palonosetron hydrochloride |
WO2011001400A3 (en) * | 2009-06-30 | 2011-05-12 | Ranbaxy Laboratories Limited | Processes for the preparation of form i and form ii of palonosetron hydrochloride |
CN114315822A (en) * | 2021-12-23 | 2022-04-12 | 北大医药股份有限公司 | Palonosetron hydrochloride hydrate crystal form and preparation method thereof |
-
2008
- 2008-01-24 CN CN2008100595276A patent/CN101255157B/en not_active Expired - Fee Related
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009087643A1 (en) * | 2008-01-11 | 2009-07-16 | Natco Pharma Limited | Novel crystalline forms of palonosetron hydrochloride |
WO2011001400A3 (en) * | 2009-06-30 | 2011-05-12 | Ranbaxy Laboratories Limited | Processes for the preparation of form i and form ii of palonosetron hydrochloride |
CN114315822A (en) * | 2021-12-23 | 2022-04-12 | 北大医药股份有限公司 | Palonosetron hydrochloride hydrate crystal form and preparation method thereof |
Also Published As
Publication number | Publication date |
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CN101255157B (en) | 2010-10-13 |
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