CN107773539A - A kind of injection CCI-779 and preparation method thereof - Google Patents
A kind of injection CCI-779 and preparation method thereof Download PDFInfo
- Publication number
- CN107773539A CN107773539A CN201610741549.5A CN201610741549A CN107773539A CN 107773539 A CN107773539 A CN 107773539A CN 201610741549 A CN201610741549 A CN 201610741549A CN 107773539 A CN107773539 A CN 107773539A
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- CN
- China
- Prior art keywords
- cci
- injection
- preparation
- ethanol
- material powder
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 title claims abstract description 45
- 229960000235 temsirolimus Drugs 0.000 title claims abstract description 45
- 238000002347 injection Methods 0.000 title claims abstract description 33
- 239000007924 injection Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000000843 powder Substances 0.000 claims abstract description 11
- 239000000463 material Substances 0.000 claims abstract description 9
- 238000004806 packaging method and process Methods 0.000 claims abstract description 5
- 239000011261 inert gas Substances 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
- 238000001035 drying Methods 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 claims description 8
- 229920005549 butyl rubber Polymers 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 230000001954 sterilising effect Effects 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 238000004140 cleaning Methods 0.000 claims description 4
- 239000000644 isotonic solution Substances 0.000 claims description 4
- 229920001971 elastomer Polymers 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 abstract description 11
- 150000001298 alcohols Chemical class 0.000 abstract description 8
- 238000009472 formulation Methods 0.000 abstract description 8
- 238000003860 storage Methods 0.000 abstract description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004615 ingredient Substances 0.000 abstract description 3
- 239000001301 oxygen Substances 0.000 abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 abstract description 3
- 239000000654 additive Substances 0.000 abstract description 2
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract 1
- 235000019441 ethanol Nutrition 0.000 description 16
- 239000002904 solvent Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 1
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 201000007455 central nervous system cancer Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to field of pharmaceutical preparations, it is related to a kind of injection CCI-779 and preparation method thereof, one kind is specifically provided to be made up of as sole component CCI-779 material powder, any additives are not added, direct packaging, and influence of the oxygen to product quality is avoided by way of vacuumizing or vacuumizing rear backfilled with inert gas.The powder-injection of the present invention shows that product quality is stable through long-term storage and accelerated test.Said preparation formulation ingredients are few, and preparation method is convenient and easy, the shortcomings that improving existing formulation and technology complexity, and drastically reduce the area the composition that alcohols etc. easily brings injection pain sense, more securely and reliably.Explanation is needed most, product made from the technology, which is stored at room temperature, can obtain high stability, Product transport of being more convenient for and Clinical practice.
Description
Technical field
The invention belongs to pharmaceutical preparations technology field, and in particular to a kind of injection CCI-779 and preparation method thereof,.
Background technology
CCI-779 is 42- pairs-hydroxymethyl propionic acid ester of rapamycin, shows cell growth Reproduction suppression in vivo
Property, the time of tumour cell development or the recurrence time of tumour can be delayed.CCI-779 is incorporated into cell protein FKBP and shape
Into complex, the complex can with inhibitory enzyme mTOR (mammal target point of rapamycin), the suppression of mTOR ' s kinase activities,
Various signal transduction pathways are inhibited, include the cell propagation of cytokine activation, adjust some keys of phase cell cycle G1
The mRNAs of protein transcription and the transcription of IL-2 inductions, are in progress, and then produce anticancer so as to suppress the cell cycle from G1 to S
Effect.
CCI-779 has been proved to be able to the growth for suppressing different tumour cells in some histologies, central nervous system
Cancer, leukaemia, mastocarcinoma, prostate cancer and melanoma are very sensitive to it.Wyeth of the U.S. has had listed smooth at present
Xi Mosi concentrated solutions, trade nameFor treating advanced renal cell carcinoma.
Patent CN1671385A, the parenteral formulation of CCI-779 is disclosed, is made up of concentrated solution and diluent, concentrated solution
Alcohols solvent containing high concentration, such as ethanol and propane diols;Also contain antioxidant;Diluent includes Tween 80, polyethylene glycol
400 and absolute ethyl alcohol etc..The patent formulation and technology complicated component, and the alcohols solvent containing higher concentration, it can bring during injection
Stronger pain.With greater need for explanation, the patented product need to be stored under 2~8 DEG C of cryogenic conditions, to production,
Transport, preserve and using bringing great limitation.
CN1829514A discloses the lyophilized formulations of CCI-779, and the freezing solvent used is selected from dimethyl sulfoxide, acetonitrile, second
Alcohol, isopropanol or the tert-butyl alcohol, it is freeze-dried to be made.Lyophilized organic solvent used is difficult to remove, either production operation or clinic
Use, easily bring potential safety hazard.
CN 103099806A disclose a kind of injection CCI-779 and preparation method thereof, by the CCI-779 of recipe quantity,
Antioxidant is dissolved in absolute ethyl alcohol, is mixed, and is added dispersant, is mixed again, after freeze-drying removes ethanol, is produced.This method
Obtained product need to be stored in 2~8 DEG C, and Clinical practice and transport are made troubles.
The content of the invention
In view of the shortcomings of the prior art, it is an object of the invention to by being ground to the physicochemical properties of CCI-779
Study carefully, look for another way, there is provided a kind of injection CCI-779 and preparation method thereof, particularly provide one kind and dispense raw material, do not add
Add the CCI-779 powder-injection of any additives.Storage and accelerated test show the powder-injection warp of the present invention for a long time, product quality
It is stable.Said preparation formulation ingredients are few, and preparation method is convenient and easy, the shortcomings that improving existing formulation and technology complexity, and significantly
Reduce the composition that alcohols etc. easily brings injection pain sense, more securely and reliably.Explanation is needed most, made from the technology
Product, which is stored at room temperature, can obtain high stability, Product transport of being more convenient for and Clinical practice.
The object of the present invention is achieved like this:A kind of CCI-779 powder-injection, it is characterised in that:By CCI-779 raw material
Powder forms as sole component.
The purpose of the present invention can also be achieved in that:Described CCI-779 material powder direct packaging, and it is true by taking out
Empty mode avoids influence of the oxygen to product quality.
The purpose of the present invention can also be achieved in that:Described CCI-779 material powder direct packaging, and it is true by taking out
The mode that inert gas is filled after sky avoids influence of the oxygen to product quality.Wherein, from the aspect of cheap and easy to get, indifferent gas
Body is preferably nitrogen.
Injection CCI-779 prepared by the present invention, needs when clinically using and diluent mixes, then with clinic
The isotonic solution used dilute again.Described diluent is ethanol, and the dosage of ethanol is 5%~20% (w/v),
W, is the weight of CCI-779, and v is the volume of ethanol;The dosage of preferred alcohol is 8%~15%;Ethanol in embodiments
Dosage elects 12% as;Described isotonic solution is useful clinically isotonic solution, usually, be 0.9% sodium chloride solution or
5% glucose solution.
The preparation method of above-mentioned injection CCI-779, comprises the following steps:
(1) first cillin bottle is cleaned, it is standby by sterilizing and drying.
(2) by butyl rubber plug through cleaning, sterilizing-drying is standby.
(3) powder of CCI-779 is filled into every cillin bottle, half adds plug, is put into freeze dryer, is freeze-dried.
(4) freeze-dried rear extraction vacuum or backfill nitrogen, tamponade, which rolls to cover, to be produced.
The application method of above-mentioned injection CCI-779, be by above-mentioned steps 4) in gained CCI-779, be dissolved in dilution
Agent, then add isotonic agent and mix, you can injection uses.
Compared with prior art, injection CCI-779 of the present invention and preparation method thereof has the following advantages that and shown
The progress of work:
(1) stability is good.Injection CCI-779 produced by the present invention, can storage and transport at ambient temperature.Pass through
Table 1 can be seen that and at ambient temperature, this product stability is significantly larger than prior art products.
(2) it is safe.Auxiliary material used in the present invention is far less than prior art, because The present invention reduces the smooth west of injection
Component in not taking charge of so that the formulation ingredients of said preparation are few, avoid higher Clinical practice risk when injection uses.
(3) patient's interdependence is strong.Due to the poorly water-soluble of CCI-779, the alcohols solvents such as ethanol need to be used to be dissolved.
Compared with patent has used substantial amounts of alcohols solvent in the prior art, because the present invention considerably reduces making for alcohols solvent
With, therefore reduce the injection pain sense that alcohols material is brought, more securely and reliably.
Specific embodiment
It is the specific embodiment of the present invention below, technical scheme is described further, but the present invention
Protection domain is not limited to these embodiments.It is every to be included in the present invention without departing substantially from the change of present inventive concept or equivalent substitute
Protection domain within.
Embodiment 1
Preparation technology:
1st, wash bottle sterilizing-drying:First by cillin bottle by ultrasonic bottle washing machine washes clean, by 320 DEG C of sterilizing drying machine
Sterilizing and drying, it is standby.
2nd, butyl rubber plug is handled:Butyl rubber plug is cleaned up through rubber plug cleaning machine, 121 DEG C of hot steam sterilizers 20 divide
Clock, drying for standby.
3rd, the powder containing CCI-779 is filled into every cillin bottle, half adds plug, is put into freeze dryer.
4th, freeze-dried machine extracts vacuum, and tamponade, which rolls to cover, to be produced.
Embodiment 2
Preparation technology:
1st, wash bottle sterilizing-drying:First by cillin bottle by ultrasonic bottle washing machine washes clean, by 320 DEG C of sterilizing drying machine
Sterilizing and drying, it is standby.
2nd, butyl rubber plug is handled:Butyl rubber plug is cleaned up through rubber plug cleaning machine, 121 DEG C of hot steam sterilizers 20 divide
Clock, drying for standby.
3rd, the powder containing CCI-779 is filled into every cillin bottle, half adds plug, is put into freeze dryer.
4th, freeze-dried machine extracts vacuum, backfills nitrogen, tamponade, which rolls to cover, to be produced.
Comparative example 1
Prepared according to following formula of the prior art:
Product is made in embodiment 1,2 and comparative example 1 and is placed in 25 DEG C, RH60% carries out study on the stability result such as
Under:
The embodiment of table 1 and comparative example study on the stability result
As can be seen that the CCI-779 injection of the invention being prepared and commercially available prodAnd prior art
(comparative example 1) compares, more stable.Products obtained therefrom stability of the present invention is higher, and facilitating storage, transport and clinic makes
With, and reducing product auxiliary material, use is safer.
Claims (10)
- A kind of 1. injection CCI-779, it is characterised in that:It is made up of CCI-779 material powder as sole component.
- 2. injection CCI-779 as claimed in claim 1, it is characterised in that:By CCI-779 material powder direct packaging, And vacuumize.
- 3. injection CCI-779 as claimed in claim 1, it is characterised in that:By CCI-779 material powder direct packaging, By filling inert gas after vacuumizing.
- 4. injection CCI-779 as claimed in claim 3, it is characterised in that:Described inert gas is nitrogen.
- 5. injection CCI-779 as claimed in claim 1, need to be dissolved in diluent when clinically using, then with clinic Available isotonic solution is diluted again.
- 6. injection CCI-779 as claimed in claim 5, it is characterised in that:Diluent is ethanol.
- 7. injection CCI-779 as claimed in claim 6, it is characterised in that:The dosage of ethanol is 5%~20% (w/v).
- 8. injection CCI-779 as claimed in claim 7, it is characterised in that:The dosage of ethanol is 8%~15%.
- 9. injection CCI-779 as claimed in claim 8, it is characterised in that the dosage of ethanol is 12%.
- 10. a kind of preparation method of the injection CCI-779 described in claim 1-9 any claims, including following step Suddenly:(1) first cillin bottle is cleaned, it is standby by sterilizing and drying;(2) butyl rubber plug is cleaned up through rubber plug cleaning machine, sterilizing-drying is standby;(3) powder of CCI-779 is filled into every cillin bottle, half adds plug, is put into freeze dryer, is freeze-dried;(4) freeze-dried rear extraction vacuum or backfill nitrogen, tamponade, which rolls to cover, to be produced.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN201610741549.5A CN107773539A (en) | 2016-08-27 | 2016-08-27 | A kind of injection CCI-779 and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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CN201610741549.5A CN107773539A (en) | 2016-08-27 | 2016-08-27 | A kind of injection CCI-779 and preparation method thereof |
Publications (1)
Publication Number | Publication Date |
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CN107773539A true CN107773539A (en) | 2018-03-09 |
Family
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Family Applications (1)
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CN201610741549.5A Pending CN107773539A (en) | 2016-08-27 | 2016-08-27 | A kind of injection CCI-779 and preparation method thereof |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1829514A (en) * | 2003-07-25 | 2006-09-06 | 惠氏公司 | CCI-779 lyophilized formulations |
CN100402031C (en) * | 2002-07-30 | 2008-07-16 | 惠氏公司 | Parenteral formulations containing a rapamycin hydroxyester |
CN102133193A (en) * | 2011-03-23 | 2011-07-27 | 山东新时代药业有限公司 | Faropenem sodium powder injection |
US20110301189A1 (en) * | 2010-06-02 | 2011-12-08 | Fresenius Kabi Oncology Ltd. | Stable pharmaceutical compositions of rapamycin esters |
CN105687132A (en) * | 2016-03-17 | 2016-06-22 | 鲁南贝特制药有限公司 | Concentrated solution for temsirolimus injection and preparation method thereof |
-
2016
- 2016-08-27 CN CN201610741549.5A patent/CN107773539A/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100402031C (en) * | 2002-07-30 | 2008-07-16 | 惠氏公司 | Parenteral formulations containing a rapamycin hydroxyester |
CN1829514A (en) * | 2003-07-25 | 2006-09-06 | 惠氏公司 | CCI-779 lyophilized formulations |
US20110301189A1 (en) * | 2010-06-02 | 2011-12-08 | Fresenius Kabi Oncology Ltd. | Stable pharmaceutical compositions of rapamycin esters |
CN102133193A (en) * | 2011-03-23 | 2011-07-27 | 山东新时代药业有限公司 | Faropenem sodium powder injection |
CN105687132A (en) * | 2016-03-17 | 2016-06-22 | 鲁南贝特制药有限公司 | Concentrated solution for temsirolimus injection and preparation method thereof |
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Application publication date: 20180309 |