CN104027791B - Pharmaceutical composition - Google Patents
Pharmaceutical composition Download PDFInfo
- Publication number
- CN104027791B CN104027791B CN201310070356.8A CN201310070356A CN104027791B CN 104027791 B CN104027791 B CN 104027791B CN 201310070356 A CN201310070356 A CN 201310070356A CN 104027791 B CN104027791 B CN 104027791B
- Authority
- CN
- China
- Prior art keywords
- cblb612
- acid
- compositions
- freeze
- drying compositions
- 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.)
- Active
Links
Abstract
The present invention relates to the medicament freeze-drying compositions with CBLB612 shown in Formulas I and pharmaceutically-acceptable salts thereof of the active component for radioprotective adjuvant drug or antitumor drug adjuvant drug.Described compositions also includes specific excipient and the pH adjusting agent of stable pH range or buffer salt system.Stability that compositions of the present invention demonstrates and medical effect, be readily transported again and store.
Description
Technical field:
The invention belongs to field of pharmaceutical preparations, specifically enter theory and relate to comprising the medicine of CBLB612 or its pharmaceutically-acceptable salts
Compositions, it is more particularly related to comprise as active component CBLB612 or its pharmaceutically-acceptable salts, specific
Excipient, extra pH adjusting agent or buffer salt system, stable pH be 5.0～8.0 medicament freeze-drying compositions.
Background technology:
The compositions of the present invention comprise the CBLB612 ester matter polypeptide with Formulas I structure as medicine activity component or its
Pharmaceutically-acceptable salts.CN101242852A disclose this ester peptide as NF-κ B inducer protection mammal from stress
Expose the purposes in (such as radiotherapy and treatment of cancer).CBLB612 is excellent
Formulas I
The synthesizing new structured lipid peptide molecule produced during changing lead compound, this molecular structure imitates sky
The mycoplasma anti-apoptosis factor so existed.As the natural product of mankind's flora, these factors may will not be produced as during medicine
Raw bad acute inflammatory reaction.Its structure is exactly ten peptide compounds containing a modification group (cetylate),
For ester matter polypeptide.Mainly by activating TLR2/TLR6 receptor complex and the signal of NF-κ B subsequently, thus suppression is normal thin
Born of the same parents are movable by the apoptosis of stress-induced.CN101242852A discloses this ester peptide and contributes to protecting hemopoietic (HP) system, increases
Add the survival rate after mice contacts fatal dose radiation with monkey.The CBLB612 by research with shielding property is found,
CBLB612, except the various modes in treatment of cancer is radiated and optionally protects the health in addition to tissue in chemotherapy, also can induce with it
With transfer hematopoietic stem cell (HSC) to relevant in peripheral blood.Relied on by TLR2 and induce some cytokines, including G-CSF
(granulocyte colony-stimulating factor) etc..The hematopoietic stem cell induction degree of CBLB612 point out the potential application of this compound more than
Anti-radiation protection is the most extensive.The actively impact of hematopoietic stem cell is contributed to it protectant as of hemopoietic system
Effect.
Preliminary Results finds, CBLB612 has outside the characteristic similar with CBLB-502, moreover it is possible in mouse and monkey
Stimulate the propagation of hematopoietic stem cell (HSC), and lure that they are passed to peripheral blood from bone marrow into.In mice and monkey are tested,
The curative effect of the CBLB612 curative effect more than G-CSF and the united curative effect of G-CSF+AMD3100 (Mozibil of Genzyme company).
This compound contributes to its protectant effect as hemopoietic system to the actively impact of hematopoietic stem cell.
The application that the hematopoietic stem cell induction degree of CBLB612 points out this compound potential is inherently more extensive, in advance more than anti-radiation protection
Meter, this compound is also the important agent of an auxiliary for treating cancer by being developed to.What is more important CBLB612 is tied
Structure more optimizes, and molecule is less, and toxic and side effects is lower, and drug combination uses safer, and treatment window is wider, and DEVELOPMENT PROSPECT is good.
Summary of the invention
The invention provides CBLB612 pharmaceutical composition, described compositions overcome CBLB612 ester matter polypeptide to light,
Wet, hot, the shortcoming of the instability such as alkali, reasonable development goes out the combination dosage form of parenterally administration, can be lyophilizing combination
Thing, for radioprotective adjuvant drug or antitumor drug adjuvant drug.
CBLB612 is ester matter polypeptide, is the U.S. gram livre orchid biology laboratory exploitation noval chemical compound, can lure as NF-κ B
Lead thing protection mammal from apoptosis etc..The present inventor conducts in-depth research result to its dissolubility and shows:
CBLB612 is soluble in water, in 0.1M sodium hydroxide dissolve, in 0.1M hydrochloric acid atomic molten, methanol, acetonitrile, ethanol,
In dichloromethane, DMF, isopropanol, the tert-butyl alcohol insoluble.CBLB612 is degraded by force again examination by the applicant
Testing research, result shows: CBLB612 stability is bad, and to sensitivity such as light, wet, hot, alkali, the most also research CBLB612 is not
With the stability under pH, experimental result is shown in Table 1.Experimental study shows: CBLB612 solution is stability under the conditions of 2～8 DEG C
Relatively 25 DEG C stable；Its stable pH range under the conditions of 2～8 DEG C is pH5.0～8.0.
Table 1CBLB612 is stability in different PH solution
By the studies above, the stability of active substance ester matter peptide C BLB612 at room temperature aqueous solution is relatively poor,
Research process finds, by adding certain excipient and using buffer salt system, can strengthen the stability of its solution, more excellent
Choosing is that this fluid composition is carried out lyophilization, is prepared as freeze-dried composition, can further enhance its stability and length
Storage period.
Therefore, the medicament freeze-drying compositions that the present invention provides, it comprises:
A) CBLB612 or its pharmaceutically acceptable salt；
B) freeze-dried excipient；
C) pH value of described compositions can be adjusted to pH adjusting agent or the buffer system of 5.0～8.0.
In medicament freeze-drying compositions of the present invention, the consumption of pH adjusting agent or buffer system is preferably shorter than the institute of 0.5 molar equivalent
State CBLB612.
Excipient is made up of one or more excipient, in the present invention preferred trehalose, sucrose, mannitol, glycine
Or its mixture, more preferably trehalose, sucrose or its mixture.The preferred excipient of the present invention and CBLB612 or its pharmaceutically
The mass ratio 1: 1～1000: 1 of acceptable salt, more preferably 5: 1～50: 1.
The compositions of the present invention adds pH adjusting agent or buffer system, active component CBLB612 can be protected further,
Its stable pH scope be selected from 5.0～8.0, preferably 6.0～7.0, more preferably 6.0～6.5.According to its stable pH range, can make
The preferred hydrochloric acid of pH adjusting agent, citric acid, acetic acid, phosphoric acid, oxalic acid, lactic acid, succinic acid, tartaric acid, malic acid, maleic acid third
Acid, sulphuric acid；PH buffer system is selected from citric acid buffer system, histidine-hydrochloride buffer system or other buffer systems.Upper
In the range of stating preferred pH, having good stability of compositions.
It addition, the invention provides CBLB612 pharmaceutical composition, preferably freeze-dried composition, can be used for preparing parenteral to
Pharmaceutically dosage form, such dosage form may be adapted to by direct injection or by being added in the aseptic transfusion of intravenous infusion
It is administered, for radioprotective adjuvant drug or antitumor drug adjuvant drug.
Present invention also offers the preparation method of composition preparing CBLB612 or pharmaceutically acceptable salt, the method include with
Lower step:
A) stable pH aqueous solution or buffer system are prepared,
B) excipient or vehicle composition are dissolved in the solution of a) step, and regulate pH to 5.0～8.0,
C) add CBLB612 or pharmaceutically acceptable salt, filter subpackage,
D) solution of lyophilizing step c.
CBLB612 ester matter polypeptide of the present invention is prepared synthesis and can be prepared as follows, and is first according to conventional polypeptide
Sequent synthesis method synthesis VQGEESNDK nonapeptide.Then by known references CN101242852A, Yukari Fujimoto,
Masahito Hashimoto, etc. (ChemBioChem2009,10,2311-2315) and Gao Huiming, Hu Yongzhou (Chinese Medicine
Industry magazine 2003,34 (10): 485-486) etc. the method for description synthesize Palmic acid and cysteine lipid bonding pad part
(with reference to CN101242852A)；Finally nonapeptide VQGEESNDK is synthesized with above-mentioned cysteine carboxy moiety.
Heretofore described CBLB612 pharmaceutically acceptable salt is the salt that CBLB612 is formed with organic acid or alkali, Qi Zhongsuo
The salt stated is preferably acetate, trifluoroacetate, citrate, tartrate, propionate, succinate, oxalates, malic acid
Salt, maleate, lactate, ammonium salt；More preferably ammonium salt.
CBLB612 ester matter polypeptide or its pharmaceutically acceptable salt are adjusted by adding the pH of excipient and stable pH5.0～8.0
Pharmaceutical composition prepared by joint agent or buffer system, it overcomes active component CBLB612 ester matter polypeptide or its pharmaceutically acceptable salt
Unstability to conditions such as light, heat, alkali, the pharmaceutical composition good stability of formation, and storage period is long, technological operation is simple,
And can by easy and efficiently method produce, final composition by direct injection or by be added to for
The aseptic transfusion of intravenous infusion is administered, for radioprotective adjuvant drug or antitumor drug adjuvant drug.
Detailed description of the invention
Invention specific embodiment presented below, simultaneously the present invention be not limited to the percentage ratio described in this, component and
Technology.
Embodiment 1
Prepared by CBLB612 ester matter polypeptide ammonium salt
Weigh a certain amount of CBLB612 sample and add 20mL deionized water dissolving, and add a certain amount of 1% isopropanol.So
After at-10 DEG C, dropping 25mL ammonia (25%c=11.1945mol/L), react 15-20min, after having reacted, remove impurity, freeze
Dry.
Embodiment 2
Excipient screening study
Prescription 2-1 is the API that subpackage is good, as comparison.Remaining prescription is formulated as follows: first prepare pH6.5 hydrochloric acid group ammonia
Acid buffer, is subsequently adding recipe quantity excipient, rear repetition measurement pH to be dissolved, is eventually adding active medicine CBLB612, dissolves
After Wan Quan, filter, subpackage, lyophilizing.Its stability is investigated at 60 DEG C.
Experiment screening result is as follows:
Experimental result shows: use any excipient such as mannitol, trehalose, sucrose, glycine, a combination thereof thing
Stability will be better than the stability of the compositions without excipient, and wherein, when using trehalose or sucrose, effect is more preferable.
Embodiment 3
Buffer salt system is screened
Prescription 3-1 is directly active medicine CBLB612 and freeze-dried excipient trehalose directly to be dissolved, subpackage, lyophilizing.I.e.
For the prescription without buffer system, as comparison.Remaining prescription compound method is as follows: first prepares pH6.5 buffer, is subsequently adding
Recipe quantity excipient, rear repetition measurement pH to be dissolved, it is eventually adding active medicine CBLB612, after dissolving completely, filters, subpackage,
Lyophilizing.Its stability is investigated at 60 DEG C.
Experiment screening result is as follows:
Experimental result shows: buffer salt system is selected from histidine/hydrochloride buffer system or citrate buffer system.
Embodiment 4
The screening of pH
Note: active medicine CBLB612 pH3.0,4.0 time, dissolubility is the lowest, can not meet effective dose, abandon screening.
PH9.0 screening study selects phosphate buffer.
Compound method is as follows: first prepare the buffer of different pH, is subsequently adding recipe quantity excipient, to be dissolved completely after
Repetition measurement pH, is eventually adding active medicine CBLB612, after dissolving completely, filters, subpackage, lyophilizing.It is investigated stable at 60 DEG C
Property.
Experiment screening result is as follows:
| PH the selection result | 0d | 5d | 10d | |
| Lot number | PH value screens | The most miscellaneous | The most miscellaneous | The most miscellaneous |
| 4-1 | 5.0 | 3.96% | 4.92% | 5.50% |
| 4-2 | 5.5 | 4.10% | 5.00% | 5.40% |
| 4-3 | 6.0 | 4.60% | 4.38% | 4.57% |
| 4-4 | 6.5 | 4.6078 | 4.342 | 4.59% |
| 4-5 | 7.0 | 4.65% | 6.57% | 4.65% |
| 4-6 | 7.5 | 4.67% | 4.42% | 4.69% |
| 4-7 | 8.0 | 4.67% | 4.36% | 4.71% |
| 4-8 | 9.0 | 5.23% | 8.15% | 12.37% |
Experimental result shows: CBLB612 pharmaceutical composition is the most stable in the range of pH5.0～8.0, but more preferably pH6.0
～between 7.0.
Embodiment 5
| Effect | Composition | Consumption |
| Active component | CBLB612 | 2mg |
| Excipient | Trehalose | 20mg |
| PH adjusting agent | Hydrochloric acid | Adjust pH6.5 |
| Solvent | Water for injection | It is settled to 2g |
First preparing pH with 0.01M hydrochloric acid solution by above-mentioned prescription is 6.5 aqueous solutions, is subsequently adding recipe quantity trehalose, treats
After dissolving completely, add active medicine CBLB612, after dissolving completely, then with 0.01M salt acid for adjusting pH to 6.5, finally fixed
Hold, filter, subpackage, lyophilizing.Nitrogen filled protection before outlet, temperature 25 DEG C ± 2.0 DEG C, under the conditions of humidity 60%R.H ± 5%R.H,
The indexs such as prescription sample can be stablized more than 3 months, impurity conform to quality requirements.Finished product after lyophilizing uses normal saline to redissolve
After, clarification, can directly inject or the aseptic transfusion of intravenous infusion is administered.
Embodiment 6
First prepare pH6.0 citrate buffer by above-mentioned prescription, be subsequently adding recipe quantity trehalose, to be dissolved completely
Rear repetition measurement pH, is eventually adding active medicine CBLB612, after dissolving completely, filters, subpackage, lyophilizing.Nitrogen filled protection before outlet,
Temperature 25 DEG C ± 2.0 DEG C, under the conditions of humidity 60%R.H ± 5%R.H, the indexs such as prescription sample can be stablized more than 3 months, impurity
Conform to quality requirements.After finished product after lyophilizing uses normal saline to redissolve, clarification, can directly inject or intravenous infusion aseptic
Transfusion is administered.
Embodiment 7
First prepare pH6.0 hydrochloric acid-histidine buffering liquid by above-mentioned prescription, be subsequently adding recipe quantity sucrose, to be dissolved complete
Repetition measurement pH after complete, is eventually adding active medicine CBLB612, after dissolving completely, filters, subpackage, lyophilizing.Nitrogen filled protection before outlet,
Temperature 25 DEG C ± 2.0 DEG C, under the conditions of humidity 60%R.H ± 5%R.H, prescription sample can be stablized more than 3 months, and impurity etc. refers to
Mark conforms to quality requirements.After finished product after lyophilizing uses normal saline to redissolve, clarification, can directly inject or the nothing of intravenous infusion
Bacterium transfusion is administered.
Embodiment 8
Compositions is prepared by embodiment 6 method, temperature 25 DEG C ± 2.0 DEG C, under the conditions of humidity 60%R.H ± 5%R.H,
The indexs such as prescription sample can be stablized more than 3 months, impurity conform to quality requirements.Finished product after lyophilizing uses normal saline to redissolve
After, clarification, can directly inject or the aseptic transfusion of intravenous infusion is administered.
Embodiment 9
Compositions is prepared by embodiment 6 method, temperature 25 DEG C ± 2.0 DEG C, under the conditions of humidity 60%R.H ± 5%R.H,
The indexs such as prescription sample can be stablized more than 6 months, impurity conform to quality requirements.Finished product after lyophilizing uses normal saline to redissolve
After, clarification, can directly inject or the aseptic transfusion of intravenous infusion is administered.
Embodiment 10
Compositions is prepared by embodiment 6 method, temperature 25 DEG C ± 2.0 DEG C, under the conditions of humidity 60%R.H ± 5%R.H,
The indexs such as prescription sample can be stablized more than 6 months, impurity conform to quality requirements.Finished product after lyophilizing uses normal saline to redissolve
After, clarification, can directly inject or the aseptic transfusion of intravenous infusion is administered.
Embodiment 11
At 60 DEG C, investigate the stability of above-described embodiment 5-10 preparation, investigate result as follows:
| 60 DEG C of influence factors | 0d/ is the most miscellaneous | 5d/ is the most miscellaneous | 10d/ is the most miscellaneous |
| API compares | 4.60% | 9.04% | 12.15% |
| Embodiment 5 | 4.51% | 4.67% | 5.18% |
| Embodiment 6 | 4.83% | 4.78% | 4.85% |
| Embodiment 7 | 4.91% | 4.70% | 4.85% |
| Embodiment 8 | 4.48% | 4.58% | 4.63% |
| Embodiment 9 | 4.51% | 4.79% | 4.81% |
| Embodiment 10 | 4.67% | 4.53% | 4.83% |
Conclusion: knowable to above example result of study, the CBLB612 pharmaceutical composition of the present invention, by adding Sargassum
The filleies such as sugar and the pH adjusting agent of stable pH5.0～8.0 particularly pH6.0～7.0 or buffer system can be prepared more
Add stable pharmaceutical composition, overcome the active component CBLB612 unstability to conditions such as light, heat, alkali, and storage period
Long, technological operation is simple, and can be produced with method efficiently by easy, and final composition is given by direct injection
Medicine or be administered in the aseptic transfusion of intravenous infusion by being added to, auxiliary for radioprotective adjuvant drug or antitumor drug
Help medication.
Claims (14)
1. one kind contains CBLB612 or the medicament freeze-drying compositions of its pharmaceutically-acceptable salts, it is characterised in that comprise:
A) CBLB612 or its pharmaceutically acceptable salt；
B) freeze-dried excipient；
C) pH value of described compositions can be adjusted to pH adjusting agent or the buffer system of 5.0～8.0.
Medicament freeze-drying compositions the most according to claim 1, wherein, the consumption of pH adjusting agent or buffer system is less than 0.5
The described CBLB612 of molar equivalent.
Medicament freeze-drying compositions the most according to claim 1 and 2, it is characterised in that the pharmacy of wherein said CBLB612
Acceptable salt is the salt formed with organic acid or alkali.
Medicament freeze-drying compositions the most according to claim 3, the pharmaceutically acceptable salt of wherein said CBLB612 is vinegar
Hydrochlorate, trifluoroacetate, citrate, tartrate, propionate, succinate, oxalates, malate, maleate, breast
Hydrochlorate, ammonium salt.
Medicament freeze-drying compositions the most according to claim 4, it is characterised in that wherein said CBLB612 pharmacy can connect
The salt being subject to is CBLB612 ammonium salt.
6. according to the medicament freeze-drying compositions according to any one of claim 1-2, it is characterised in that wherein said excipient
Selected from trehalose, sucrose, mannitol or glycine one or more.
Medicament freeze-drying compositions the most according to claim 6, wherein said excipient selected from trehalose or sucrose or it
Mixture.
8. according to the medicament freeze-drying compositions according to any one of claim 1-2, it is characterised in that wherein said excipient
It is 1: 1～1000: 1 with the mass ratio of CBLB612 or its pharmaceutically-acceptable salts.
Medicament freeze-drying compositions the most according to claim 8, wherein said excipient and CBLB612 or its pharmaceutically may be used
The mass ratio accepting salt is 5: 1～50: 1.
10. according to the pharmaceutical composition according to any one of claim 1-2, it is characterised in that wherein said pH adjusting agent
Selected from hydrochloric acid, citric acid, acetic acid, phosphoric acid, oxalic acid, lactic acid, succinic acid, tartaric acid, malic acid, maleic acid propanoic acid, sulphuric acid.
11. according to the medicament freeze-drying compositions according to any one of claim 1-2, it is characterised in that wherein said pH delays
System of rushing is selected from citric acid buffer system, histidine-hydrochloride buffer system.
Medicament freeze-drying compositions according to any one of 12. claim 1-2, wherein said pH scope be preferably 6.0～
7.0。
The compositions according to any one of 13. claim 1-12 purposes in preparation radioprotective or antitumor drug.
The method of 14. preparations medicament freeze-drying compositions described in claim 1, it is characterised in that the method comprises the following steps:
A) stable pH aqueous solution or buffer system are prepared,
B) excipient or vehicle composition are dissolved in the solution of a step, and regulate pH to 5.0～8.0,
C) add CBLB612 or pharmaceutically acceptable salt, filter subpackage,
D) solution of lyophilizing step c.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310070356.8A CN104027791B (en) | 2013-03-06 | 2013-03-06 | Pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310070356.8A CN104027791B (en) | 2013-03-06 | 2013-03-06 | Pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104027791A CN104027791A (en) | 2014-09-10 |
| CN104027791B true CN104027791B (en) | 2016-08-10 |
Family
ID=51458935
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310070356.8A Active CN104027791B (en) | 2013-03-06 | 2013-03-06 | Pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104027791B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101631850A (en) * | 2007-01-09 | 2010-01-20 | 克里夫兰生物实验室公司 | The method of increase and mobilizing hematopoietic stem cells |
| CN102712677A (en) * | 2009-11-23 | 2012-10-03 | 丘比斯特药物股份有限公司 | Lipopeptide compositions and related methods |
-
2013
- 2013-03-06 CN CN201310070356.8A patent/CN104027791B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101631850A (en) * | 2007-01-09 | 2010-01-20 | 克里夫兰生物实验室公司 | The method of increase and mobilizing hematopoietic stem cells |
| CN102712677A (en) * | 2009-11-23 | 2012-10-03 | 丘比斯特药物股份有限公司 | Lipopeptide compositions and related methods |
Non-Patent Citations (1)
| Title |
|---|
| 《细菌抗菌肽的研究进展及其应用》;马文山，等;《生物技术通报》;20080331(第3期);39-49 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104027791A (en) | 2014-09-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW200306205A (en) | Lyophilised preparation comprising antibodies against the EGF receptor | |
| CN102961745B (en) | Antibody composition preparation and application thereof | |
| CZ20003089A3 (en) | Stable solution containing oxaliplatin, process of its preparation, pharmaceutical preparation containing thereof and use thereof | |
| EA016653B1 (en) | Methods and compositions for inhibiting angiogenesis | |
| US11224631B2 (en) | Ready-to-use Carfilzomib compositions | |
| JP2020531410A (en) | Daptomycin preparation | |
| EP4019023A1 (en) | Formulations of fosaprepitant and aprepitant | |
| WO2012103802A1 (en) | Liquid medicinal composition containing echinocandin antifungal agent micafungin | |
| US11141421B2 (en) | Antitumor agent for biliary tract cancer and method for treating biliary tract cancer | |
| JP2024045148A (en) | Compositions Containing Somatostatin Analogs for Use in Radiopharmaceuticals - Patent application | |
| CN104027791B (en) | Pharmaceutical composition | |
| WO2017133706A1 (en) | De-epoxidized epothilone derivative preparation, preparation of same and use thereof in the treatment of tumour | |
| EP2934593B1 (en) | Cabazitaxel composition | |
| WO2007134533A1 (en) | 20(R)-GINSENOSIDE Rg3 MEDICINAL SOLUBLE INTERMEDIATE AND PROCESS THEREOF | |
| WO2016045570A2 (en) | Pharmaceutical composition of humanized antibody for vascular endothelial growth factor | |
| WO2023107706A1 (en) | Stat3 degraders and uses thereof | |
| KR20200052326A (en) | Formulation of Copanlis | |
| CN108187069A (en) | A kind of voriconazole pharmaceutical composition and its preparation | |
| TW201440783A (en) | Pharmaceutical composition comprising micafungin or the salts thereof | |
| CN103980279A (en) | Methotrexate compound and methotrexate for injection | |
| CN113082203B (en) | Liquid preparation of immunosuppressant monoclonal antibody | |
| CN1398183A (en) | Medicament contg. platinum complex compounds and use thereof | |
| CN104829653B (en) | A kind of oxaliplatin hydrate crystal and lyophilized injectable powder thereof | |
| TWI634897B (en) | Pharmaceutical composition of micafungin or the salts thereof | |
| TW202345827A (en) | Irak4 degraders and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |