CN101584669A - Melphalan freeze-dried powder injection - Google Patents
Melphalan freeze-dried powder injection Download PDFInfo
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- CN101584669A CN101584669A CNA2009100338962A CN200910033896A CN101584669A CN 101584669 A CN101584669 A CN 101584669A CN A2009100338962 A CNA2009100338962 A CN A2009100338962A CN 200910033896 A CN200910033896 A CN 200910033896A CN 101584669 A CN101584669 A CN 101584669A
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Abstract
The invention relates to a melphalan freeze-dried powder injection and a preparing method thereof. The prepared melphalan freeze-dried powder injection is used for treating multiple myeloma, oophoroma, polycythemia vera, local malignant melanoma and soft tissue sarcoma. The melphalan freeze-dried powder injection contains melphalan, utilizes the mixed solvent composed of the tert-butyl alcohol and the injection water in the preparation process, wherein the concentration of the melphalan in the mixed solvents is 10-25 mg/ml; and the volume ratio of the solvents is: 5-50% of tert-butyl alcohol and the balance of injection water. The preparation process comprises the following steps: measuring tert-butyl alcohol, adding injection water, mixing evenly, cooling to 2-15 DEG C, heat preserving, adding melphalan, stirring and dripping 0.5 mol hydrochloric acid to dissolve, filtering, filling, plugging, disking, freeze-drying, pressing plug, out box, tying and packing after quality test qualification.
Description
Technical field
What the present invention relates to is a kind of melphalan freeze-dried powder injection and preparation method thereof, melphalan freeze-dried powder injection by this method preparation can be used as multiple myeloma, ovarian cancer, the true too much disease of property erythrocyte, local malignant melanoma, and the medicine of soft tissue sarcoma.
Background technology
Melphalan be the levo form phenylpropyl alcohol by sour chlormethine, its anticarcinogenic effect is pressed PAM for strong, its mechanism of action is identical with HN2, also is cell cycle nonspecific agent (CCNSA).Oral absorption is abundant, and the back 2 hours blood plasma of taking medicine reaches Gao Xiaodu, keeps in blood plasma active about 6 hours, and 50% the medicine of taking medicine in 24 hours is through homaluria, and wherein 13% is original shape, and metabolite is a hydroxyl derivant and a dihydroxyl derivative.
Injection is used for multiple myeloma, ovarian cancer, the true too much disease of property erythrocyte, local malignant melanoma, and the treatment of soft tissue sarcoma.
Melphalan is that white is to buff powder, be insoluble in water, to light, heat and unstable under moisture conditions, so can only make lyophilized injectable powder, but because melphalan is insoluble in water, need to add acid in the process for preparation and make its salify dissolving, common preparation method melphalan in process for preparation is degraded in a large number, makes curative effect of medication reduce and produce the impurity of initiation toxic and side effects.Existing known technology does not improve the suggestion of above defective yet.
Summary of the invention
The objective of the invention is provides a kind of melphalan freeze-dried powder injection and preparation method thereof at above weak point, can improve the stability of melphalan freeze-dried powder injection greatly by this method, make it in preparation, transportation and storage process, have better stability, avoided the hidden danger of bringing because of drug degradation that curative effect reduces and degraded generation impurity brings for patient's drug safety.
The chemical name of melphalan is: L-3{ is to [two (2-chloroethyl) amido] phenyl } alanine, structural formula is:
Molecular formula is: C
13H
18Cl
2N
2O
2
Molecular weight is: 305.20.
A kind of melphalan freeze-dried powder injection contains melphalan, and the mixed solvent that uses the tert-butyl alcohol and water for injection to form in process for preparation, and wherein melphalan is 10～25mg/ml in the concentration of mixed solvent, and the volume proportion of solvent is:
The tert-butyl alcohol 5～50%
The water for injection surplus
Total amount 100%.
A kind of melphalan freeze-dried powder injection, the volume proportion of described solvent is:
The tert-butyl alcohol 10～30%
The water for injection surplus
Total amount 100%.
A kind of melphalan freeze-dried powder injection also contains excipient.
A kind of melphalan freeze-dried powder injection, described excipient is selected from mannitol, lactose, dextran and glucose.
A kind of melphalan freeze-dried powder injection, its preparation process is:
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 2～15 ℃ and insulation, add melphalan again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 2～4 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 2～4 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
A kind of melphalan freeze-dried powder injection of the present invention and preparation method thereof, can improve the stability of melphalan freeze-dried powder injection greatly by this method in preparation process, the melphalan freeze-dried powder injection its related substances of preparation is lower, the quality stable homogeneous, moisture drying is thorough, stability in transportation and storage process is better, and curative effect reduction and the degraded also having avoided simultaneously bringing because of drug degradation produce the hidden danger that impurity brings for patient's drug safety.Preparation technology of the present invention is simple, and is convenient feasible, good reproducibility, and production cost is lower, is easy to realize industrialized great production, thereby can produce considerable economic and social benefit.
The specific embodiment
Further specify the present invention below by embodiment.Should correct understanding be: embodiments of the invention are only used for the present invention is described and provide, rather than limitation of the present invention, so, under method prerequisite of the present invention, simple modifications of the present invention is all belonged to the scope of protection of present invention.
Embodiment 1:
Prescription
Melphalan 50g
Tert-butyl alcohol 400ml
Water for injection adds to 2000ml
Make 1000 bottles altogether
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 8 ℃ and insulation, add melphalan again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 3 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 3 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
Embodiment 2:
Prescription
Melphalan 50g
Mannitol 100g
Tert-butyl alcohol 1200ml
Water for injection adds to 4000ml
Make 1000 bottles altogether
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 6 ℃ and insulation, add melphalan and mannitol again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 4 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 2 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
Embodiment 3:
Prescription
Melphalan 50g
Mannitol 200g
Tert-butyl alcohol 200ml
Water for injection adds to 2000ml
Make 1000 bottles altogether
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 2 ℃ and insulation, add melphalan and mannitol again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 4 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 3 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
Embodiment 4:
Prescription
Melphalan 50g
Mannitol 200g
Tert-butyl alcohol 250ml
Water for injection adds to 5000ml
Make 1000 bottles altogether
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 15 ℃ and insulation, add melphalan and mannitol again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 2 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 4 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
Embodiment 5:
Prescription
Melphalan 50g
Glucose 150g
Tert-butyl alcohol 800ml
Water for injection adds to 2000ml
Make 1000 bottles altogether
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 2 ℃ and insulation, add melphalan and glucose again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 2 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 4 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
Embodiment 6:
Prescription
Melphalan 50g
Glucose 100g
Tert-butyl alcohol 400ml
Water for injection adds to 2000ml
Make 1000 bottles altogether
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 6 ℃ and insulation, add melphalan and glucose again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 4 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 2 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
Embodiment 7:
Prescription
Melphalan 50g
Lactose 50g
Tert-butyl alcohol 1500ml
Water for injection adds to 3000ml
Make 1000 bottles altogether
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 8 ℃ and insulation, add melphalan and lactose again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 3 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 4 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
Embodiment 8:
Prescription
Melphalan 50g
Lactose 100g
Tert-butyl alcohol 600ml
Water for injection adds to 2000ml
Make 1000 bottles altogether
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 6 ℃ and insulation, add melphalan and lactose again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 34 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 3 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
Embodiment 9:
Prescription
Melphalan 50g
Dextran 10 0g
Tert-butyl alcohol 800ml
Water for injection adds to 2000ml
Make 1000 bottles altogether
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 2 ℃ and insulation, add melphalan and dextran again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 2 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 2 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
Embodiment 10:
Prescription
Melphalan 50g
Dextran-20 0g
Tert-butyl alcohol 500ml
Water for injection adds to 5000ml
Make 1000 bottles altogether
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 8 ℃ and insulation, add melphalan and dextran again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 3 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 4 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
Embodiment 11:
Respectively prepare melphalan freeze-dried powder injection respectively by embodiment 1～10, check its outward appearance, visible foreign matters, particulate matter, content, related substance and moisture more respectively, it the results are shown in Table 1.
Table 1 melphalan freeze-dried powder injection check result
Claims (5)
1, a kind of melphalan freeze-dried powder injection is characterized in that containing melphalan, and the mixed solvent that uses the tert-butyl alcohol and water for injection to form in process for preparation, and wherein melphalan is 10～25mg/ml in the concentration of mixed solvent, and the volume proportion of solvent is:
The tert-butyl alcohol 5～50%
The water for injection surplus
Total amount 100%.
2, melphalan freeze-dried powder injection according to claim 1 is characterized in that the volume proportion of described solvent is:
The tert-butyl alcohol 10～30%
The water for injection surplus
Total amount 100%.
3, melphalan freeze-dried powder injection according to claim 1 is characterized in that also containing excipient.
4, melphalan freeze-dried powder injection according to claim 3 is characterized in that described excipient is selected from a kind of in mannitol, lactose, dextran, the glucose.
5, the preparation method of the described melphalan freeze-dried powder injection of claim 1 is characterized in that preparation method is:
Measuring tert-butyl alcohol is put in the container, add water for injection, stir and mix homogeneously, mixed solvent is cooled to 2～15 ℃ and insulation, add melphalan again, the hydrochloric acid that stirs and drip 0.5mol makes its dissolving, after mix homogeneously is treated the intermediate passed examination, deliver in the sterilizing room filtering with microporous membrane through 0.22 μ m to clear and bright with peristaltic pump, fill is in brown cillin bottle, part is butyl rubber bung beyond the Great Wall, sabot; Sabot is treated that the lyophilizing sample puts in the freeze drying box, close chamber door, start, open circulating pump, compressor and plate low temperature valve utilize conduction oil that products temperature is descended, when products temperature reaches-40 ℃, the closing plate low temperature valve, open electrical heating and mix low temperature valve and be provided with automatically, kept this products temperature 2～4 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum system, the current box vacuum reaches 20Pa when following, begins the sublimation drying that heats up, last baking temperature is 28 ℃, kept this temperature 2～4 hours, after the case vacuum does not have significant change before valve in close, tamponade, outlet, with plastic-aluminum composite cover tying, packing after quality inspection is qualified, promptly.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910033896 CN101584669B (en) | 2009-06-19 | 2009-06-19 | Melphalan freeze-dried powder injection |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910033896 CN101584669B (en) | 2009-06-19 | 2009-06-19 | Melphalan freeze-dried powder injection |
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| CN101584669A true CN101584669A (en) | 2009-11-25 |
| CN101584669B CN101584669B (en) | 2010-12-29 |
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|---|---|---|---|
| CN 200910033896 Expired - Fee Related CN101584669B (en) | 2009-06-19 | 2009-06-19 | Melphalan freeze-dried powder injection |
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| CN101856325A (en) * | 2010-06-11 | 2010-10-13 | 上海丽思化工科技有限公司 | Hydrochloric acid melphalan injection liquid and preparation method thereof |
| WO2012004438A1 (en) * | 2010-07-05 | 2012-01-12 | Capital, Business Y Gestión De Finanzas, S.L. | Injectable pharmaceutical formulation of melphalan |
| WO2014065751A1 (en) * | 2012-10-26 | 2014-05-01 | Oncopeptides Ab | Lyophilized preparations of melphalan flufenamide |
| CN103920148A (en) * | 2014-04-24 | 2014-07-16 | 山东新华医疗器械股份有限公司 | Freeze-drying technology of monoclonal antibody |
| RU2597154C2 (en) * | 2011-04-28 | 2016-09-10 | Онкопептайдс Аб | Lyophilised preparation of cytotoxic dipeptides |
| KR20200081440A (en) * | 2012-10-26 | 2020-07-07 | 온코펩타이드즈 아베 | Lyophilized preparations of melphalan flufenamide |
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| CN101204366A (en) * | 2007-11-29 | 2008-06-25 | 济南帅华医药科技有限公司 | Melphalan sustained-release implant treating for solid tumor |
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| WO2012004438A1 (en) * | 2010-07-05 | 2012-01-12 | Capital, Business Y Gestión De Finanzas, S.L. | Injectable pharmaceutical formulation of melphalan |
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| EP2928463A4 (en) * | 2012-10-26 | 2016-08-31 | Oncopeptides Ab | Lyophilized preparations of melphalan flufenamide |
| KR20200081440A (en) * | 2012-10-26 | 2020-07-07 | 온코펩타이드즈 아베 | Lyophilized preparations of melphalan flufenamide |
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| CN108685860B (en) * | 2012-10-26 | 2022-04-05 | 肿瘤多肽股份公司 | Lyophilized formulation of melphalan flufenamide |
| CN103920148A (en) * | 2014-04-24 | 2014-07-16 | 山东新华医疗器械股份有限公司 | Freeze-drying technology of monoclonal antibody |
| CN103920148B (en) * | 2014-04-24 | 2016-06-22 | 山东新华医疗器械股份有限公司 | A kind of freeze drying process of monoclonal antibody formulation |
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| CN101584669B (en) | 2010-12-29 |
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Address after: 211112 Jiangsu Province, Nanjing City, Jiangning Science Park Road No. 699 Patentee after: Jiangsu Aosaikang Pharmaceutical Co., Ltd. Address before: 211112 Jiangsu Province, Nanjing City, Jiangning Science Park Road No. 699 Patentee before: Jiangsu Aosaikang Pharmaceutical Co., Ltd. |
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