CN109966244A - A kind of pharmaceutical composition containing Le Temowei - Google Patents
A kind of pharmaceutical composition containing Le Temowei Download PDFInfo
- Publication number
- CN109966244A CN109966244A CN201711440869.8A CN201711440869A CN109966244A CN 109966244 A CN109966244 A CN 109966244A CN 201711440869 A CN201711440869 A CN 201711440869A CN 109966244 A CN109966244 A CN 109966244A
- Authority
- CN
- China
- Prior art keywords
- temowei
- pharmaceutical composition
- added
- injection
- composition containing
- 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
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 21
- 239000004475 Arginine Substances 0.000 claims abstract description 23
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 23
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 claims abstract description 11
- 235000017281 sodium acetate Nutrition 0.000 claims abstract description 11
- 229940087562 sodium acetate trihydrate Drugs 0.000 claims abstract description 11
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 25
- 239000007864 aqueous solution Substances 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000007924 injection Substances 0.000 claims description 15
- 238000002347 injection Methods 0.000 claims description 15
- 239000000706 filtrate Substances 0.000 claims description 14
- 239000008215 water for injection Substances 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 238000005261 decarburization Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- 239000002510 pyrogen Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- 239000003963 antioxidant agent Substances 0.000 claims description 6
- 230000003078 antioxidant effect Effects 0.000 claims description 6
- 235000006708 antioxidants Nutrition 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 4
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 3
- 235000010265 sodium sulphite Nutrition 0.000 claims description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 1
- -1 ammonia Acid Chemical class 0.000 claims 1
- 238000010790 dilution Methods 0.000 abstract description 8
- 239000012895 dilution Substances 0.000 abstract description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 4
- 239000002504 physiological saline solution Substances 0.000 abstract description 4
- 229940093181 glucose injection Drugs 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 230000010494 opalescence Effects 0.000 abstract description 2
- 229940090044 injection Drugs 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000012360 testing method Methods 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 102000004452 Arginase Human genes 0.000 description 3
- 108700024123 Arginases Proteins 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- LGACUMPRRMLUFZ-UHFFFAOYSA-N 1,4-dihydroquinazoline Chemical compound C1=CC=C2CN=CNC2=C1 LGACUMPRRMLUFZ-UHFFFAOYSA-N 0.000 description 1
- PZIBVWUXWNYTNL-UHFFFAOYSA-N 1-(3-methoxyphenyl)piperazine Chemical compound COC1=CC=CC(N2CCNCC2)=C1 PZIBVWUXWNYTNL-UHFFFAOYSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- FWYSMLBETOMXAG-QHCPKHFHSA-N letermovir Chemical compound COC1=CC=CC(N2CCN(CC2)C=2N([C@@H](CC(O)=O)C3=CC=CC(F)=C3N=2)C=2C(=CC=C(C=2)C(F)(F)F)OC)=C1 FWYSMLBETOMXAG-QHCPKHFHSA-N 0.000 description 1
- 229950010668 letermovir Drugs 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- JWHHANVGNNWIRI-UHFFFAOYSA-N methanol phosphoric acid hydrate Chemical compound O.OC.OP(O)(O)=O JWHHANVGNNWIRI-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- DGPIGKCOQYBCJH-UHFFFAOYSA-M sodium;acetic acid;hydroxide Chemical compound O.[Na+].CC([O-])=O DGPIGKCOQYBCJH-UHFFFAOYSA-M 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 108010040614 terminase Proteins 0.000 description 1
- 239000012085 test solution 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K9/08—Solutions
-
- 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)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to pharmaceutical technology fields, and the present invention provides a kind of pharmaceutical composition containing Le Temowei, described pharmaceutical composition includes Le Temowei, arginine and sodium acetate trihydrate.Pharmaceutical composition of the present invention is suitable for mass production；The stability of pharmaceutical composition of the present invention is good, occurs with after physiological saline or the dilution of 5% glucose injection without opalescence or turbid phenomenon.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to pharmaceutical composition and its preparation containing Le Temowei.
Background technique
Cytomegalovirus (CMV) widespread in the mankind, in the case where immunological incompetence or immune deficiency (as transplanting by
Person), it may cause the infection of serious threat to life.Cmv infection is characterized in fever, oligoleukocythemia and decrease of platelet, together
When with or be not accompanied by organ dysfunction.
In November, 2017, FDA ratify antiviral drugs letermovir (Le Temowei) listing of MSD Corp..It is happy special
It is multiple to terminate enzyme (terminase) by targeting virus for a new class of non-nucleoside CMV inhibitor of Mo Wei (3,4- dihydroquinazoline)
The duplication that object inhibits virus is closed, for preventing cytomegalovirus infection.
Chemical entitled (S)-[the fluoro- 2- of 8- [4- (3- methoxyphenyl) piperazine -1- base] 3- (2- methoxyl group-of Le Temowei
5- trifluoromethyl) -3,4- dihydroquinazoline -4- base] acetic acid, molecular formula C29H28F4N4O4, molecular weight 572.55, molecule
Structure is as follows:
Summary of the invention
The present invention provides a kind of composition containing Le Temowei, the composition includes Le Temowei, arginine and three
Water sodium acetate.
It include injection, freeze-dried powder the present invention provides there is preparation made of the above-mentioned composition containing Le Temowei
Or infusion.
The present invention also provides the methods for preparing preparation made of the above-mentioned composition containing Le Temowei.
What the present invention was achieved through the following technical solutions.
A kind of pharmaceutical composition containing Le Temowei, it is characterised in that include Le Temowei, arginine and three water acetic acid
Sodium.
The weight ratio of the Le Temowei and arginine, sodium acetate trihydrate are 1:(0.9-1.2): (0.3-0.7).
The composition also includes antioxidant.
The antioxidant is in sodium thiosulfate, ascorbic acid and its derivative, sodium sulfite, sodium pyrosulfite
It is one or more of.
The pH of the aqueous solution of the composition is 5.7-6.3.
A kind of pharmaceutical composition containing Le Temowei is prepared into pharmaceutical preparation, including injection, freeze-dried powder.
A method of preparing the pharmaceutical preparation of the pharmaceutical composition containing Le Temowei, comprising the following steps:
1) arginine is weighed, appropriate water for injection is added, makes it completely dissolved, obtains arginine aqueous solution；
2) Le Temowei is dissolved in the resulting arginine aqueous solution of step 1), is made it completely dissolved；
3) sodium acetate trihydrate is added in the resulting solution of step 2), is made it completely dissolved；
4) pH to 5.7-6.3 is adjusted, water for injection is added to configuration amount；
5) proper amount of active carbon is added, stirring removes pyrogen removal, filters decarburization, obtains filtrate；
6) by step 5) acquired solution aseptic filtration, filtrate is obtained, filling, get Le Temowei injection；
7) the resulting Le Temowei injection of step 6) arbitrarily, is freeze-dried to obtain freeze-dried powder.
It further include that antioxidant is added in step 3).
Pharmaceutical composition of the invention can also be containing pharmaceutically common various additives, as long as the additive does not hinder
The function of Le Temowei.Representative additive includes, but are not limited to: chelating agent, pH adjusting agent etc..
Compared with the prior art, the present invention has the following advantages and good effect:
1, the present invention provides a kind of new composition containing Le Temowei；
2, pharmaceutical composition of the present invention is suitable for mass production；
3, the stability of pharmaceutical composition of the present invention is good, after physiological saline or the dilution of 5% glucose injection
No opalescence or turbid phenomenon occur.
Specific embodiment
The following describes the present invention further through the description of specific embodiments, but it is to limit of the invention that this, which is not,
System, those skilled in the art's basic thought according to the present invention can make various modifications or improvements, but without departing from this
The basic thought of invention, is all within the scope of the present invention.
Prepare embodiment
Embodiment 1
1) arginine 18.0g is weighed, appropriate 160ml water for injection is added, makes it completely dissolved, obtains arginine aqueous solution；
2) Le Temowei 20g is dissolved in the resulting arginine aqueous solution of step 1), is made it completely dissolved；
3) sodium acetate trihydrate 6g is added in the resulting solution of step 2), is made it completely dissolved；
4) pH to 5.7 is adjusted with sodium hydroxide, water for injection 40ml is added to configuration amount；
5) proper amount of active carbon is added, stirring removes pyrogen removal, filters decarburization, obtains filtrate；
6) by step 5) acquired solution aseptic filtration, filtrate is obtained, filling, get Le Temowei injection.
Embodiment 2
1) arginase 12 1.4g is weighed, appropriate 160ml water for injection is added, makes it completely dissolved, obtains arginine aqueous solution；
2) Le Temowei 20g is dissolved in the resulting arginine aqueous solution of step 1), is made it completely dissolved；
3) sodium acetate trihydrate 8g, sodium thiosulfate 0.8g are added in the resulting solution of step 2), are made it completely dissolved；
4) pH to 6.0 is adjusted with sodium hydroxide, water for injection 40ml is added to configuration amount；
5) proper amount of active carbon is added, stirring removes pyrogen removal, filters decarburization, obtains filtrate；
6) by step 5) acquired solution aseptic filtration, filtrate is obtained, filling, get Le Temowei injection；
7) the resulting Le Temowei injection of step 6) is freeze-dried to obtain freeze-dried powder.
Embodiment 3
1) arginase 12 3.7g is weighed, appropriate 160ml water for injection is added, makes it completely dissolved, obtains arginine aqueous solution；
2) Le Temowei 20g is dissolved in the resulting arginine aqueous solution of step 1), is made it completely dissolved；
3) sodium acetate trihydrate 7.2g, ascorbic acid 0.6g are added in the resulting solution of step 2), are made it completely dissolved；
4) pH to 6.1 is adjusted, water for injection 40ml is added to configuration amount；
5) proper amount of active carbon is added, stirring removes pyrogen removal, filters decarburization, obtains filtrate；
6) by step 5) acquired solution aseptic filtration, filtrate is obtained, filling, get Le Temowei injection.
Embodiment 4
1) arginase 12 0g is weighed, appropriate 160ml water for injection is added, makes it completely dissolved, obtains arginine aqueous solution；
2) Le Temowei 20g is dissolved in the resulting arginine aqueous solution of step 1), is made it completely dissolved；
3) sodium acetate trihydrate 6g, sodium sulfite 1.0g are added in the resulting solution of step 2), are made it completely dissolved；
4) pH to 6.2 is adjusted, water for injection 40ml is added to configuration amount；
5) proper amount of active carbon is added, stirring removes pyrogen removal, filters decarburization, obtains filtrate；
6) by step 5) acquired solution aseptic filtration, filtrate is obtained, filling, get Le Temowei injection；
7) the resulting Le Temowei injection of step 6) is freeze-dried to obtain freeze-dried powder.
Embodiment 5
1) arginine 18g is weighed, appropriate 160ml water for injection is added, makes it completely dissolved, obtains arginine aqueous solution；
2) Le Temowei 20g is dissolved in the resulting arginine aqueous solution of step 1), is made it completely dissolved；
3) sodium acetate trihydrate 14g, sodium pyrosulfite 0.5g are added in the resulting solution of step 2), are made it completely dissolved；
4) pH to 6.3 is adjusted, water for injection 40ml is added to configuration amount；
5) proper amount of active carbon is added, stirring removes pyrogen removal, filters decarburization, obtains filtrate；
6) by step 5) acquired solution aseptic filtration, filtrate is obtained, filling, get Le Temowei injection.
1 stability test of test example
Related substance takes this product appropriate, and the solution in every 1ml containing about 2mg is made with flowing phase dilution, molten as test sample
Liquid；Precision measures in right amount, is quantitatively diluted and is made containing about the solution of 2 μ g in every 1ml, as contrast solution with mobile phase.According to efficient
Liquid chromatography (two V D of annex of Chinese Pharmacopoeia version in 2010) test, is filler with octadecylsilane chemically bonded silica；With
Water (with phosphorus acid for adjusting pH value to 2.5)-acetonitrile (1340:680) is mobile phase；Detection wavelength is 234nm；Flow velocity 2ml/min.Claim
Seek pleasure Te Mowei reference substance 20mg, sets in 10ml measuring bottle, is diluted to scale with mobile phase, shakes up, as system suitability
Solution measures 20 μ l and injects liquid chromatograph, records chromatogram；20 μ l of contrast solution is measured, liquid chromatograph is injected, adjusts inspection
Sensitivity is surveyed, making the peak height of principal component chromatographic peak is about the 10% of full scale；It is accurate again to measure test solution and contrast solution
Each 20 μ l is injected separately into liquid chromatograph, records chromatogram.
[assay] is measured according to high performance liquid chromatography (two annex V D of Chinese Pharmacopoeia version in 2010).
Chromatographic condition and system suitability are filler with octadecylsilane chemically bonded silica；With phosphoric acid-water-methanol
(3:247:750) (being diluted with water to 1000ml) is mobile phase；Detection wavelength is 274nm；Flow velocity 1.5ml/min.Number of theoretical plate
It is calculated by the peak Le Temowei and is not less than 2500.
It is appropriate that measuring method precision measures this product, sets in 50ml measuring bottle, is made in every 1ml with flowing phase dilution containing Le Temowei
The solution of 2mg, precision measure 20 μ l, inject liquid chromatograph, record chromatogram；Another Te Mowei reference substance of seeking pleasure, is measured in the same method.
By external standard method with calculated by peak area to get.
Embodiment 1, embodiment 3, embodiment 5 are respectively at 60 DEG C of influence factor experimental condition high temperature, illumination (5000lx) item
It places 10 days under part, is measured by sampling after 5,10 days.Character, pH value, particulate matter, content, related substance are detected, with
Sample compares within 0 day.
1 estimation of stability result of table (0 day)
| It checks | Embodiment 1 | Embodiment 3 | Comparative example 5 |
| Character | Colourless clear liquid | Colourless clear liquid | Colourless clear liquid |
| PH value | 6.08 | 6.16 | 6.27 |
| Related substance % | 0.06 | 0.06 | 0.07 |
| Content (%) | 100.7 | 101.1 | 101.0 |
2 estimation of stability result of table (5 days)
3 estimation of stability result of table (10 days)
From the foregoing, it will be observed that the product of the present invention stability with higher after high temperature, illumination.
Clarity test after the dilution of 2 sample of test example
Each 4ml of sample of Example 1, embodiment 3, embodiment 5 uses 100ml physiological saline, the Portugal 100m l5% respectively
After the dilution of grape sugar injection, clarity of solution is observed after placing 8 hours, the results are shown in Table 4.
Clarity after being stood 4 hours after the dilution of 4 sample of table
Conclusion: after sample of the present invention 100ml physiological saline, the dilution of 5% glucose injection of 100ml, solution clarification,
It places 4 hours, solution is still clarified；Since clinical use needs to control transfusion speed, therefore the present invention has apparent advantage, more
Safe ready.
Claims (8)
1. a kind of pharmaceutical composition containing Le Temowei, which is characterized in that described pharmaceutical composition includes Le Temowei, smart ammonia
Acid and sodium acetate trihydrate.
2. a kind of pharmaceutical composition containing Le Temowei according to claim 1, which is characterized in that the Le Temo
The weight ratio of Wei and arginine, sodium acetate trihydrate is 1:(0.9-1.2): (0.3-0.7).
3. a kind of pharmaceutical composition containing Le Temowei according to claim 1, which is characterized in that the composition is also
Include antioxidant.
4. a kind of pharmaceutical composition containing Le Temowei according to claim 3, it is characterised in that the antioxidant
Selected from one or more of sodium thiosulfate, ascorbic acid and its derivative, sodium sulfite, sodium pyrosulfite.
5. a kind of pharmaceutical composition containing Le Temowei according to claim 1, it is characterised in that the composition
The pH of aqueous solution is 5.7-6.3.
6. a kind of pharmaceutical composition containing Le Temowei according to claim 1 is prepared into pharmaceutical preparation, including injection
Liquid, freeze-dried powder.
7. a kind of method for the pharmaceutical composition for preparing claim 1, comprising the following steps:
1) arginine is weighed, appropriate water for injection is added, makes it completely dissolved, obtains arginine aqueous solution；
2) Le Temowei is dissolved in the resulting arginine aqueous solution of step 1), is made it completely dissolved；
3) sodium acetate trihydrate is added in the resulting solution of step 2), is made it completely dissolved；
4) pH to 6.9-7.6 is adjusted, water for injection is added to configuration amount；
5) proper amount of active carbon is added, stirring removes pyrogen removal, filters decarburization, obtains filtrate；
6) by step 5) acquired solution aseptic filtration, filtrate is obtained, filling, get Le Temowei injection；
7) the resulting Le Temowei injection of step 6) arbitrarily, is freeze-dried to obtain freeze-dried powder.
8. preparation method according to claim 7 further includes that antioxidant is added in step 3).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711440869.8A CN109966244A (en) | 2017-12-27 | 2017-12-27 | A kind of pharmaceutical composition containing Le Temowei |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711440869.8A CN109966244A (en) | 2017-12-27 | 2017-12-27 | A kind of pharmaceutical composition containing Le Temowei |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109966244A true CN109966244A (en) | 2019-07-05 |
Family
ID=67072097
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711440869.8A Pending CN109966244A (en) | 2017-12-27 | 2017-12-27 | A kind of pharmaceutical composition containing Le Temowei |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109966244A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111024861A (en) * | 2019-12-31 | 2020-04-17 | 山东省药学科学院 | Detection method of Latemovir and related substances in Latemovir-containing preparation |
| WO2021170875A1 (en) * | 2020-02-27 | 2021-09-02 | Aic246 Gmbh & Co. Kg | Pharmaceutical compositions comprising 2-[(4s)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4h-quinazolin-4-yl]acetate and sodium ions |
| WO2021170878A1 (en) * | 2020-02-27 | 2021-09-02 | Aic246 Gmbh & Co. Kg | Sodium 2-[(4s)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4h-quinazolin-4-yl]acetate and pharmaceutical compositions thereof |
| US11420976B2 (en) | 2020-01-24 | 2022-08-23 | Enanta Pharmaceuticals, Inc. | Heterocyclic compounds as anti-viral agents |
| US11505558B1 (en) | 2019-10-04 | 2022-11-22 | Enanta Pharmaceuticals, Inc. | Antiviral heterocyclic compounds |
| US11534439B2 (en) | 2020-07-07 | 2022-12-27 | Enanta Pharmaceuticals, Inc. | Dihydroquinoxaline and dihydropyridopyrazine derivatives as RSV inhibitors |
| US11912695B2 (en) | 2019-03-18 | 2024-02-27 | Enanta Pharmaceuticals, Inc. | Benzodiazepine derivatives as RSV inhibitors |
| US11945824B2 (en) | 2020-10-19 | 2024-04-02 | Enanta Pharmaceuticals, Inc. | Heterocyclic compounds as anti-viral agents |
| US11945830B2 (en) | 2021-02-26 | 2024-04-02 | Enanta Pharmaceuticals, Inc. | Antiviral heterocyclic compounds |
| US11952389B2 (en) | 2015-07-22 | 2024-04-09 | Enanta Pharmaceuticals, Inc. | Benzodiazepine derivatives as RSV inhibitors |
-
2017
- 2017-12-27 CN CN201711440869.8A patent/CN109966244A/en active Pending
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12297209B2 (en) | 2015-07-22 | 2025-05-13 | Enanta Pharmaceuticals, Inc. | Benzodiazepine derivatives as RSV inhibitors |
| US11952389B2 (en) | 2015-07-22 | 2024-04-09 | Enanta Pharmaceuticals, Inc. | Benzodiazepine derivatives as RSV inhibitors |
| US11912695B2 (en) | 2019-03-18 | 2024-02-27 | Enanta Pharmaceuticals, Inc. | Benzodiazepine derivatives as RSV inhibitors |
| US11505558B1 (en) | 2019-10-04 | 2022-11-22 | Enanta Pharmaceuticals, Inc. | Antiviral heterocyclic compounds |
| US12006326B2 (en) | 2019-10-04 | 2024-06-11 | Enanta Pharmaceuticals, Inc. | Antiviral heterocyclic compounds |
| CN111024861A (en) * | 2019-12-31 | 2020-04-17 | 山东省药学科学院 | Detection method of Latemovir and related substances in Latemovir-containing preparation |
| US11420976B2 (en) | 2020-01-24 | 2022-08-23 | Enanta Pharmaceuticals, Inc. | Heterocyclic compounds as anti-viral agents |
| CN115427024A (en) * | 2020-02-27 | 2022-12-02 | Aic246股份两合公司 | 2- [ (4S) -8-fluoro-2- [4- (3-methoxyphenyl) piperazin-1-yl ] -3- [ 2-methoxy-5- (trifluoromethyl) phenyl ] -4H-quinazolin-4-yl ] sodium acetate and pharmaceutical compositions thereof |
| CN115515565A (en) * | 2020-02-27 | 2022-12-23 | Aic246股份两合公司 | Pharmaceutical composition comprising 2- [ (4S) -8-fluoro-2- [4- (3-methoxyphenyl) piperazin-1-yl ] -3- [ 2-methoxy-5- (trifluoromethyl) phenyl ] -4H-quinazolin-4-yl ] acetate and sodium ions |
| JP2023520627A (en) * | 2020-02-27 | 2023-05-18 | アーイーツェー２４６ アクチェンゲゼルシャフト ウント コンパニー コマンディトゲゼルシャフト | 2-[(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4H-quinazoline- Sodium 4-yl]acetate and pharmaceutical compositions thereof |
| WO2021170878A1 (en) * | 2020-02-27 | 2021-09-02 | Aic246 Gmbh & Co. Kg | Sodium 2-[(4s)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4h-quinazolin-4-yl]acetate and pharmaceutical compositions thereof |
| JP7592734B2 (en) | 2020-02-27 | 2024-12-02 | アーイーツェー２４６ アクチェンゲゼルシャフト ウント コンパニー コマンディトゲゼルシャフト | Sodium 2-[(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4H-quinazolin-4-yl]acetate and pharmaceutical compositions thereof |
| WO2021170875A1 (en) * | 2020-02-27 | 2021-09-02 | Aic246 Gmbh & Co. Kg | Pharmaceutical compositions comprising 2-[(4s)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-4h-quinazolin-4-yl]acetate and sodium ions |
| US11534439B2 (en) | 2020-07-07 | 2022-12-27 | Enanta Pharmaceuticals, Inc. | Dihydroquinoxaline and dihydropyridopyrazine derivatives as RSV inhibitors |
| US11945824B2 (en) | 2020-10-19 | 2024-04-02 | Enanta Pharmaceuticals, Inc. | Heterocyclic compounds as anti-viral agents |
| US11945830B2 (en) | 2021-02-26 | 2024-04-02 | Enanta Pharmaceuticals, Inc. | Antiviral heterocyclic compounds |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109966244A (en) | A kind of pharmaceutical composition containing Le Temowei | |
| EP2842957A1 (en) | Method for extracting and separating ginkgolides | |
| CN110715995B (en) | Method for detecting impurities of multivitamin injection | |
| CN101957345A (en) | Method for detecting active ingredients in American cockroach extract | |
| CN113740446B (en) | Cefaclor oxime and related substance analysis method for maintaining degradation quality of preparation content | |
| CN101623293A (en) | Medical composition for injection | |
| CN105085570A (en) | Tedizolid phosphate compound and preparation method thereof | |
| CN107308119A (en) | Safe ten thousand rhzomorph particles of a kind of highly-water-soluble tartaric acid and preparation method thereof | |
| CN102379886A (en) | Scutellarin clinical preparation and preparation method thereof | |
| CN102824345B (en) | Irinotecan hydrochloride composition and preparation method thereof | |
| CN101623284A (en) | Medical composition of compound vitamin C injection | |
| CN102846704B (en) | A Leonurus japonicus injection, its preparation method, and method for detecting total alkaloids | |
| CN105434370B (en) | Triptolide chitosan nano and preparation method thereof | |
| CN103728389B (en) | HPLC method is used to measure the method for butyric acid and sodium butyrate | |
| Sultan et al. | Stability Assessment of Cephradine Suspension Formulated in Bangladesh | |
| CN102269749A (en) | Method for detecting adenosine content in hericium erinaceus tablet | |
| CN1772089B (en) | Freeze dried oldenlandia powder for injection and its preparation method | |
| CN112730680B (en) | Method for determining dissolution curve of mycophenolate mofetil | |
| CN114539289B (en) | Cefepime arginine polymer and preparation method and application thereof | |
| CN111929379B (en) | Method for identifying base source of uncaria rhynchophylla medicinal material | |
| CN102793676A (en) | Sesquiterpene lactone (1 beta, 10 beta-epoxy-13-alpha-dimethylamino-1,2-propanediol 3-(4)-alkene-6,12-lactone) dimethylamine hydrochloride freeze-drying preparation for injection and preparation method for sesquiterpene lactone (1 beta, 10 beta-epoxy-13-alpha-dimethylamino-1,2-propanediol 3-(4)-alkene-6,12-lactone) dimethylamine hydrochloride freeze-drying preparation | |
| CN105527357A (en) | Method for determining antioxidant BHT in insulin glargine injection | |
| CN112858519A (en) | Detection method for related substances of amoxicillin potassium clavulanate granules | |
| CN102755290A (en) | Medicine composition containing ibuprofen | |
| CN104177456B (en) | A kind of azithromycin medicine material and preparation and purposes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190705 |
|
| WD01 | Invention patent application deemed withdrawn after publication |