CN113559058A - Gemcitabine amino acid injection - Google Patents
Gemcitabine amino acid injection Download PDFInfo
- Publication number
- CN113559058A CN113559058A CN202110869024.0A CN202110869024A CN113559058A CN 113559058 A CN113559058 A CN 113559058A CN 202110869024 A CN202110869024 A CN 202110869024A CN 113559058 A CN113559058 A CN 113559058A
- Authority
- CN
- China
- Prior art keywords
- gemcitabine
- injection
- amino acid
- glutamic acid
- acid injection
- 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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- 229960005277 gemcitabine Drugs 0.000 title claims abstract description 80
- 238000002347 injection Methods 0.000 title claims abstract description 59
- 239000007924 injection Substances 0.000 title claims abstract description 59
- -1 Gemcitabine amino acid Chemical class 0.000 title claims abstract description 30
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims abstract description 66
- 235000001014 amino acid Nutrition 0.000 claims abstract description 41
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 37
- 239000004220 glutamic acid Substances 0.000 claims abstract description 35
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims abstract description 34
- 235000013922 glutamic acid Nutrition 0.000 claims abstract description 34
- 230000002378 acidificating effect Effects 0.000 claims abstract description 14
- 150000001413 amino acids Chemical class 0.000 claims abstract description 13
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims abstract description 11
- 235000003704 aspartic acid Nutrition 0.000 claims abstract description 11
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 10
- 229940024606 amino acid Drugs 0.000 claims description 36
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 claims description 14
- 235000013923 monosodium glutamate Nutrition 0.000 claims description 14
- 229940073490 sodium glutamate Drugs 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 abstract description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 16
- 239000000243 solution Substances 0.000 abstract description 14
- 230000007794 irritation Effects 0.000 abstract description 13
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 5
- 206010061218 Inflammation Diseases 0.000 abstract description 4
- 230000004054 inflammatory process Effects 0.000 abstract description 4
- 230000002792 vascular Effects 0.000 abstract description 3
- 229960005144 gemcitabine hydrochloride Drugs 0.000 description 15
- 230000001954 sterilising effect Effects 0.000 description 8
- 238000001914 filtration Methods 0.000 description 7
- 229940049906 glutamate Drugs 0.000 description 7
- 229930195712 glutamate Natural products 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 239000008215 water for injection Substances 0.000 description 7
- 238000004806 packaging method and process Methods 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 150000004712 monophosphates Chemical class 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000008174 sterile solution Substances 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 241000581650 Ivesia Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
Classifications
-
- 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
- A61K9/08—Solutions
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The invention relates to gemcitabine amino acid injection, and belongs to the technical field of pharmaceutical preparations. Gemcitabine amino acid injection, which comprises the following components: gemcitabine and acidic amino acids. The acidic amino acid is glutamic acid or aspartic acid; glutamic acid is preferred. The solubility of the gemcitabine glutamic acid injection prepared by the invention can reach 20-40mg/ml, and the solubility is good by preparing an acidic amino acid solution in the solution. The gemcitabine glutamic acid injection prepared by the invention has pH4-5, good physical and chemical stability, no vascular irritation to patients and no pain and irritation inflammation on the upper arm of the injected medicament. The water soluble preparation has convenient use, less pollution, simple preparation process and low cost.
Description
Technical Field
The invention relates to gemcitabine amino acid injection, and belongs to the technical field of pharmaceutical preparations.
Background
Gemcitabine hydrochloride (Gemcitabine), chemical name 2 ' -deoxy-2 ', 2 ' -difluoroadenosine hydrochloride. Gemcitabine hydrochloride is an antitumor drug produced by Lilly pharmaceutical factories in the United states. The FDA approved in 1996 as a first-line drug for treating pancreatic cancer is the most widely used anti-tumor drug for treating solid tumors.
Gemcitabine is insoluble in water and in order to increase water solubility, gemcitabine hydrochloride needs to be prepared. Gemcitabine is non-covalently bound to hydrochloric acid and is formulated with gemcitabine, hydrochloric acid and sodium acetate, the pH of the gemcitabine hydrochloride solution being 3.5 to keep the gemcitabine from precipitating and separating out of the solution. Increasing the pH of the solution causes rapid precipitation of gemcitabine. However, the injection solution with pH of 3.5 has serious irritation to blood vessel, skin and mucosa, and most patients have upper arm irritation pain and irritation inflammation of transfusion blood vessel after intravenous injection of gemcitabine hydrochloride. Experiments prove that the irritation of gemcitabine hydrochloride is caused by over-high acidity. The gemcitabine hydrochloride aqueous solution used at present is unstable under acidic and alkaline conditions, is easy to decompose and cannot be stored for a long time, so that the gemcitabine hydrochloride aqueous solution can only be prepared into a freeze-dried powder preparation, and the freeze-dried powder preparation has a complex process and high cost.
Disclosure of Invention
The present invention aims at providing gemcitabine amino acid injection to solve the above problems.
In order to achieve the purpose, the invention adopts the technical scheme that:
gemcitabine amino acid injection comprises the following components: gemcitabine and acidic amino acids.
The technical scheme of the invention is further improved as follows: the acidic amino acid is glutamic acid or aspartic acid; glutamic acid is preferred.
The technical scheme of the invention is further improved as follows: the composition of gemcitabine and glutamic acid has a molar ratio of 1: (0.6-1.2); preferably 1: 1.
the technical scheme of the invention is further improved as follows: the gemcitabine and the aspartic acid are prepared in a molar ratio of 1: (0.6-1.2); preferably 1: 1.
the technical scheme of the invention is further improved as follows: adding sodium glutamate to adjust pH of the injection; gemcitabine, glutamic acid: the mol ratio of the sodium glutamate to the sodium glutamate is 1:1 (0.1-0.6); preferably 1:1 (0.1-0.2).
The technical scheme of the invention is further improved as follows: the pH of the injection is 4-6, preferably 5.
The technical scheme of the invention is further improved as follows: the drug concentration of gemcitabine amino acid injection is 18-22 mg/ml.
The technical scheme of the invention is further improved as follows: the drug concentration of gemcitabine amino acid injection is 20 mg/ml.
Due to the adoption of the technical scheme, the invention has the following technical effects:
the solubility of the gemcitabine glutamic acid injection prepared by the invention can reach 20-40mg/ml, and the solubility is good by preparing an acidic amino acid solution in the solution. The preparation has a concentration of 20mg/ml and a specification of 10 ml/piece, and is very convenient to use.
The gemcitabine glutamic acid injection prepared by the invention has pH4-5, good physical and chemical stability, no vascular irritation to patients and no pain and irritation inflammation on the upper arm of the injected medicament. The water soluble preparation is convenient to use and reduces pollution. And compared with the freeze-dried powder preparation, the preparation method has the advantages of simple process and cost saving.
The invention uses glutamic acid or aspartic acid as acidic amino acid, and the glutamic acid or aspartic acid is one of 18 amino acids in organisms and is nontoxic. They are acidic in water, for example, the pH3.2 of glutamic acid solution is the cosolvent of gemcitabine, and gemcitabine amino acid injection is prepared, so that the solubility of gemcitabine is improved. The gemcitabine prepared by the invention has good solubility.
Detailed Description
In order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the invention is further described with the specific embodiments.
The present invention aims at providing gemcitabine aqua for injection with excellent solubility, irritation, stable property and simple technological process. The research of the patent shows that the acidic amino acid glutamic acid has two carboxyl groups and an isoelectric point of 3.2, is a good cosolvent of gemcitabine and is mutually solubilized with the gemcitabine. The acidity of the solution prepared by the two is nonirritant, and the ratio of gemcitabine: glutamic acid =1:1 ratio, gemcitabine dissolves well, and the pH of the solution is greater than 4. Sodium glutamate can be used for adjusting pH of the injection to 4.5-5.5 as required. The gemcitabine glutamic acid water solution is prepared with the concentration of 20-40 mg/ml.
Gemcitabine amino acid injection, which comprises the following components: gemcitabine and acidic amino acids. The acidic amino acid is glutamic acid or aspartic acid; glutamic acid is preferred.
When the gemcitabine and the glutamic acid are composed of the gemcitabine amino acid injection, the molar ratio of the gemcitabine amino acid injection to the glutamic acid is set as 1: (0.6-1.2); preferably 1: 1.
when the gemcitabine and the aspartic acid are composed of the gemcitabine amino acid injection, the molar ratio of the gemcitabine amino acid injection to the aspartic acid is set to be 1: (0.6-1.2); preferably 1: 1.
the gemcitabine amino acid injection of the present invention is usually added with sodium glutamate to adjust the pH of the injection. Gemcitabine, when added sodium glutamate: the mol ratio of the sodium glutamate to the sodium glutamate is 1:1 (0.1-0.6); preferably 1:1 (0.1-0.2).
The gemcitabine amino acid injection is prepared by adjusting the pH value of the injection to 4-6, preferably 5.
The drug concentration control range of the gemcitabine amino acid injection of the invention is 18-22 mg/ml. Preferably at a concentration of 20 mg/ml.
The preparation method of the preparation comprises a heating step, a pH value adjusting step and a heating sterilization or filtration sterilization step.
The preparation method of the preparation of the invention comprises the steps of adding 263mg of gemcitabine alkali and 147mg of glutamic acid into 10ml of distilled water for injection, adjusting the pH to 5 by using a sodium glutamate solution, and supplementing the water for injection to 13.2ml, wherein the gemcitabine concentration is 20 mg/ml. Filtering with 0.45 micron filter membrane to remove gas, sterilizing at 121 deg.C or sterilizing with 0.22 micron filter membrane, packaging, and storing to obtain gemcitabine-glutamic acid water solution preparation.
1) Gemcitabine glutamate injection stability (physical stability): dissolving the medicine with water for injection, and dissolving the aqueous solution preparation of the citabine glutamic acid at a concentration of 20-40 mg/ml. The temperature is 20 ℃ at room temperature, and no precipitation is generated after 20mg/ml long-term standing. 2) Gemcitabine glutamate injection stability (chemical stability); the content of the experimental sample is 20mg/ml, the sample is sterilized at 100 ℃ for 30 minutes, the content change before and after sterilization and after being placed at 45 ℃ for 3 months is observed, the concentration before the experiment is taken as 100 percent, and the results are shown in the following table.
| Sample composition | pH of the sample | Standing at 45 deg.C | 30 minutes at 100 DEG C |
| Gemcitabine glutamic acid injection | 4.0 | 99.8 | 99.9 |
| Gemcitabine glutamic acid injection | 5.0 | 99.9 | 99.8 |
| Gemcitabine hydrochloride injection | 3.5 | 94.3 | 89.6 |
The gemcitabine hydrochloride injection in the above table is a currently general reagent, and the gemcitabine hydrochloride injection is used as a comparison. As can be seen from the comparative data in the above table, the gemcitabine solubility of gemcitabine glutamate injection is good, and the solubility is greatly improved compared with that of the conventional gemcitabine hydrochloride injection.
4) Study on irritation of gemcitabine glutamate injection
Gemcitabine hydrochloride and gemcitabine glutamate injection (pH 5) were injected intravenously into mice, and red swelling of mice tails was observed after 24 hours. There was no red swelling irritation change in the mouse tail given gemcitabine glutamate injection; the red swelling of the tail of the mouse given gemcitabine hydrochloride is obvious. Gemcitabine hydrochloride instillation in clinical patients often causes arm pain, and gemcitabine glutamate injection can avoid the side effect.
The invention has the beneficial effects that:
the solubility of the gemcitabine glutamic acid injection prepared by the invention can reach 20-40mg/ml, and the solubility is good; the preparation has a concentration of 20mg/ml and a specification of 10 ml/piece, and is very convenient to use. Gemcitabine glutamic acid injection has pH4-5, good physical and chemical stability, no vascular irritation to patients, and no pain and irritation inflammation on upper arm of injected medicine. The water soluble preparation is convenient to use and reduces pollution. And compared with the freeze-dried powder preparation, the preparation method is simple in process and can save cost.
The invention is further illustrated by the following examples.
Example 1
The pharmaceutical preparation of the invention comprises the following components:
gemcitabine (base) monophosphate 263 g;
147g of glutamic acid;
adding water for injection to 1315 ml;
slightly heating to accelerate dissolution, filtering with 0.22 micron membrane to obtain sterile liquid, and packaging in 200mg/10 ml/vial.
Example 2
The pharmaceutical preparation of the invention comprises the following components:
gemcitabine (base) monophosphate 263 g;
147g of glutamic acid;
50g of sodium glutamate;
adding water for injection to 1315ml, heating slightly to accelerate dissolution, filtering with 0.22 micron membrane to obtain sterile solution, subpackaging, and packaging in 200mg/10 ml/penicillin bottle. Sterilizing at 100 deg.C for 30 min.
Example 3
The pharmaceutical preparation of the invention comprises the following components:
gemcitabine (base) monophosphate 263 g;
133g of aspartic acid;
adding water for injection to 1315ml, heating slightly to accelerate dissolution, filtering with 0.22 micron membrane to obtain sterile solution, subpackaging, and packaging in 200mg/10 ml/penicillin bottle. Sterilizing at 100 deg.C for 30 min.
Example 4
The pharmaceutical preparation of the invention comprises the following components:
6575g gemcitabine (base) monophosphate;
glutamic acid 3675 g;
125g of sodium glutamate;
adding water for injection to 32.875L, slightly heating to accelerate dissolution, filtering with 0.22 μm membrane to obtain sterile solution, packaging, and bottling in 200mg/10 ml/vial. Sterilizing at 100 deg.C for 30 min.
Example 5
The pharmaceutical preparation of the invention comprises the following components:
gemcitabine (base) monophosphate 1315 g;
882g of glutamic acid;
adding water for injection to 6575 ml;
slightly heating to accelerate dissolution, filtering with 0.22 micron membrane to obtain sterile liquid, and packaging in 200mg/10 ml/vial.
The gemcitabine amino acid injection prepared in the embodiment has no side effects such as red swelling pain and the like after use, and the injection has good stability and solubility.
The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (8)
1. Gemcitabine amino acid injection is characterized in that: the composition is as follows: gemcitabine and acidic amino acids.
2. Gemcitabine amino acid injection as claimed in claim 1, wherein: the acidic amino acid is glutamic acid or aspartic acid; glutamic acid is preferred.
3. Gemcitabine amino acid injection as claimed in claim 2, wherein: the composition of gemcitabine and glutamic acid has a molar ratio of 1: (0.6-1.2); preferably 1: 1.
4. gemcitabine amino acid injection as claimed in claim 2, wherein: the gemcitabine and the aspartic acid are prepared in a molar ratio of 1: (0.6-1.2); preferably 1: 1.
5. gemcitabine amino acid injection as claimed in claim 3, wherein: adding sodium glutamate to adjust pH of the injection; gemcitabine, glutamic acid: the mol ratio of the sodium glutamate to the sodium glutamate is 1:1 (0.1-0.6); preferably 1:1 (0.1-0.2).
6. Gemcitabine amino acid injection according to any one of claims 1-5, wherein: the pH of the injection is 4-6, preferably 5.
7. Gemcitabine amino acid injection according to any one of claims 1-5, wherein: the drug concentration of gemcitabine amino acid injection is 18-22 mg/ml.
8. Gemcitabine amino acid injection according to claim 7, wherein: the drug concentration of gemcitabine amino acid injection is 20 mg/ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110869024.0A CN113559058A (en) | 2021-07-30 | 2021-07-30 | Gemcitabine amino acid injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110869024.0A CN113559058A (en) | 2021-07-30 | 2021-07-30 | Gemcitabine amino acid injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113559058A true CN113559058A (en) | 2021-10-29 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110869024.0A Pending CN113559058A (en) | 2021-07-30 | 2021-07-30 | Gemcitabine amino acid injection |
Country Status (1)
| Country | Link |
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| CN (1) | CN113559058A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114796132A (en) * | 2022-05-13 | 2022-07-29 | 海南灵康制药有限公司 | Lyophilized powder injection of huperzine A and its preparation method |
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| US20050267066A1 (en) * | 2002-11-06 | 2005-12-01 | Cyclacel Limited | Pharmaceutical composition comprising a CDK inhibitor and gemcitabine |
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| CN109481691A (en) * | 2018-11-20 | 2019-03-19 | 珠海天香苑生物科技发展股份有限公司 | Gemcitabine-carboxymethyl polysaccharide conjugate, preparation method and its usage |
| CN110870918A (en) * | 2018-08-31 | 2020-03-10 | 成都夸常奥普医疗科技有限公司 | Pharmaceutical composition containing amino acid nutrients and antitumor chemotherapeutic drugs and application thereof |
| CN112516078A (en) * | 2020-12-12 | 2021-03-19 | 江苏集萃分子工程研究院有限公司 | Gemcitabine monophosphate solution preparation and application |
-
2021
- 2021-07-30 CN CN202110869024.0A patent/CN113559058A/en active Pending
Patent Citations (5)
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| US20050267066A1 (en) * | 2002-11-06 | 2005-12-01 | Cyclacel Limited | Pharmaceutical composition comprising a CDK inhibitor and gemcitabine |
| CN105311051A (en) * | 2014-05-26 | 2016-02-10 | 陈松源 | Carrier solvent having antitumor drug treatment effect increasing function, preparation method and administration route thereof |
| CN110870918A (en) * | 2018-08-31 | 2020-03-10 | 成都夸常奥普医疗科技有限公司 | Pharmaceutical composition containing amino acid nutrients and antitumor chemotherapeutic drugs and application thereof |
| CN109481691A (en) * | 2018-11-20 | 2019-03-19 | 珠海天香苑生物科技发展股份有限公司 | Gemcitabine-carboxymethyl polysaccharide conjugate, preparation method and its usage |
| CN112516078A (en) * | 2020-12-12 | 2021-03-19 | 江苏集萃分子工程研究院有限公司 | Gemcitabine monophosphate solution preparation and application |
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| Title |
|---|
| 张波等: "吉西他滨治疗骨肉瘤研究进展", 《国际骨科学杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114796132A (en) * | 2022-05-13 | 2022-07-29 | 海南灵康制药有限公司 | Lyophilized powder injection of huperzine A and its preparation method |
| CN114796132B (en) * | 2022-05-13 | 2023-08-22 | 海南灵康制药有限公司 | Huperzine A freeze-dried powder injection and preparation method thereof |
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Application publication date: 20211029 |