CN107789324A - A kind of injection De Lasha star meglumines and preparation method thereof - Google Patents
A kind of injection De Lasha star meglumines and preparation method thereof Download PDFInfo
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- CN107789324A CN107789324A CN201610780347.1A CN201610780347A CN107789324A CN 107789324 A CN107789324 A CN 107789324A CN 201610780347 A CN201610780347 A CN 201610780347A CN 107789324 A CN107789324 A CN 107789324A
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- lasha
- injection
- meglumines
- meglumine
- star
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- 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
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
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- 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
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- 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
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Abstract
The invention belongs to pharmaceutical technology field, and in particular to injection De Lasha star meglumines and preparation method thereof.Injection De Lasha star meglumines provided by the invention：Mainly it is made up of De Lasha stars meglumine, meglumine, sulfobutyl ether beta cyclodextrin, Ergol, pH adjusting agent and water for injection.Technical solution of the present invention filling amount is small, facilitates production and transportation, while reduces the medical treatment cost of patient in Clinical practice；Present invention reduces the usage amount of sulfobutyl ether beta cyclodextrin, therefore further increase security of the product in Clinical practice.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to injection De Lasha star meglumines and preparation method thereof.
Background technology
De Lasha star (English names：Delafloxacin) it is the wide spectrum fluorine of new generation developed by Rib-X drugmakers
Carbostyril family antibacterial drugs, the double blinding II phase clinical study results carried out for 150 cSSSIs inpatients are shown：Every 12 is small
When be injected intravenously this product 300mg, 450mg, be used in conjunction 5-14 days, to the cure rate of cSSSIs patient respectively up to 97.2% He
92.5%, tigecycline (tigecycine) group is 91.2%.This product to the antibacterial activities of the MRSA of resistance to QNS bacterium extremely
Be less lavo-ofloxacin, Ciprofloxacin, gatifloxacin, MOXIFLOXACIN 32 times (MIC90≤0.5ug/mL of this product, it is above-mentioned its
His medicine MIC90 is all higher than 16ug/mL)；And it is 2 times of Daptomycin to MRSA antibacterial activity.
The A of Chinese patent publication No. CN 103705942 and the A of publication No. CN 104958296 disclose injection De Lasha
The antimicrobial compositions of star meglumine, it improves De Lasha stars using the inclusion technique of sulfobutyl ether-beta-cyclodextrin and existed
Solubility in the aqueous solution, its solubility in water is set to reach 25mg/ml, because its every 12 hours are injected intravenously in clinic
This product 300mg, 450mg, while in order to keep the sufficient quantity in preparation use, the specification of injection De Lasha star meglumine preparations
500mg is preferred, and its loading amount is 20ml, thus needs more than 60ml container next filling, so adds Clinical practice
The treatment cost of middle patient, and bring great inconvenience to production and transportation.
If it is possible to improve the solubility of De Lasha stars meglumine in aqueous, loading amount is reduced, uses small dimension
Container come filling, can effectively improve the production of units quantity of injection De Lasha star meglumines, accelerate speed of production, solution
The inconvenience determined in the production brought because packing container is excessive, transport and use.
The content of the invention
For above-mentioned produced problem, the invention provides a kind of injection De Lasha star meglumines：Mainly by activity into
Divide De Lasha stars meglumine, meglumine, sulfobutyl ether-beta-cyclodextrin, Ergol, pH adjusting agent and water for injection composition.
The concentration range of the De Lasha stars meglumine is 50mg/ml~100mg/ml, preferably 75mg/ml；
The mass ratio of the De Lasha stars meglumine and sulfobutyl ether-beta-cyclodextrin is that scope is 1:1.2~1:1.6, it is excellent
Elect 1 as:1.4；
The Ergol and the mass ratio of sulfobutyl ether-beta-cyclodextrin stated is that scope is 1:3~1:2, preferably 1:
2.5；
Described De Lasha stars meglumine (being counted using De Lasha stars) and the mass ratio of meglumine is 1:0.1~1:0.5, preferably
For 1:0.15；
Described pH adjusting agent is one or more of mixed solutions in hydrochloric acid, phosphoric acid, acetic acid or citric acid, is preferably
Hydrochloric acid；
Described pH scopes are 7.0~8.0, preferably 7.5.
Invention further provides the preparation method of above-mentioned injection De Lasha star meglumines, mainly including following step
Suddenly：The Ergol of recipe quantity is weighed, addition is cooled in the appropriate water for injection of room temperature, stirred in advance, adds recipe quantity
Sulfobutyl ether-beta-cyclodextrin, heating stirs, and adds recipe quantity De Lasha stars meglumine, meglumine, and insulated and stirred is to complete
Fully dissolved, pH value is adjusted, total amount is settled to, stirs；Filtering, filling, freeze-drying, visual inspection is got product.
Above-mentioned purpose of the present invention has advantages below：
1. filling amount of the present invention is small, filling using the cillin bottle of small dimension, facilitate production and transportation, while reduce clinic
The medical treatment cost of patient in use；
2. because sulfobutyl ether-beta-cyclodextrin has certain hemolytic and carcinogenicity, and there may be it is unknown more
Serious toxic side effect, present invention reduces the usage amount of sulfobutyl ether-beta-cyclodextrin, therefore further increase product and facing
Security in bed use.
Embodiment
Embodiment 1：
Prescription
Preparation technology
The Ergol of recipe quantity is weighed, adds in appropriate water for injection, stirs, adds the sulphur butyl of recipe quantity
Ether-beta-schardinger dextrin, heating stir, and add recipe quantity De Lasha stars meglumine, meglumine, insulated and stirred 15min can be extremely
It is completely dissolved, adjusts pH value to 7.0 with watery hydrochloric acid or diluted sodium hydroxide solution, be settled to total amount, stir；Filtering, it is filling,
Freeze-drying, visual inspection are got product.
Embodiment 2：
Prescription
Preparation method (with embodiment 1)
Embodiment 3：
Prescription
Preparation method (with embodiment 1)
Embodiment 4：
Prescription
Preparation technology (with embodiment 1)
Embodiment 5：
Prescription
Preparation method (with embodiment 1)
Embodiment 6：
Prescription
Preparation method (with embodiment 1)
Embodiment 7：
Prescription
Preparation method (with embodiment 1)
Comparative example 1：
Prescription
Preparation method
The sulfobutyl ether-beta-cyclodextrin of recipe quantity is weighed, is added in appropriate water for injection, stirring and dissolving, adds recipe quantity
De Lasha stars meglumine, meglumine, stirring adjust pH value to 9.0 to being completely dissolved, with watery hydrochloric acid or dilute meglumine solution, constant volume
To total amount, stir；Filtering, filling, freeze-drying, visual inspection is got product.
Comparative example 2：
Prescription
Preparation method weighs the Ergol of recipe quantity, adds in water for injection, and to dissolving, heating stirring is equal for stirring
It is even, recipe quantity De Lasha stars meglumine, meglumine are added, insulated and stirred 60min, De Lasha star meglumine is not completely dissolved, is used
Watery hydrochloric acid or diluted sodium hydroxide solution adjust pH value to 7.5, are settled to total amount, insulated and stirred 60min, De Lasha star meglumine is still
It is not completely dissolved.
Comparative example 3：
Prescription
Preparation method weighs the Ergol 45.00g of recipe quantity, and addition is cooled in the 600ml waters for injection of room temperature in advance,
Stirring heating stirring 15min, adds recipe quantity De Lasha star meglumines 75.00g, meglumine 11.25g, insulated and stirred to dissolving
60min, De Lasha star meglumine are not completely dissolved, are adjusted pH value to 9.0 with watery hydrochloric acid or diluted sodium hydroxide solution, are settled to total
Amount, insulated and stirred 60min, De Lasha star meglumine are not completely dissolved yet.
Comparative example 4：
Prescription
Preparation method weighs the sulfobutyl ether-beta-cyclodextrin 105.00g of recipe quantity, adds the pre- 600ml notes for being cooled to room temperature
Penetrate with water, stirring heating stirring 15min, adds recipe quantity De Lasha star meglumines 75.00g, meglumine to dissolving
11.25g, insulated and stirred 60min, De Lasha star meglumine are not completely dissolved, and pH is adjusted with watery hydrochloric acid or diluted sodium hydroxide solution
Value is settled to total amount, insulated and stirred 60min, De Lasha star meglumine is not completely dissolved yet to 7.5.
Comparative example 5：
Prescription
Preparation method weighs the sulfobutyl ether-beta-cyclodextrin 105.00g of recipe quantity, adds the pre- 600ml notes for being cooled to room temperature
Penetrate with water, stirring heating stirring 15min, adds recipe quantity De Lasha star meglumines 75.00g, meglumine to dissolving
11.25g, insulated and stirred 60min, De Lasha star meglumine are not completely dissolved, and pH is adjusted with watery hydrochloric acid or diluted sodium hydroxide solution
Value is settled to total amount, insulated and stirred 60min, De Lasha star meglumine is not completely dissolved yet to 9.0.
Comparative example 6：
Prescription
Preparation method weighs the Ergol of recipe quantity, adds in appropriate water for injection, and to dissolving, heating is stirred for stirring
15min, recipe quantity De Lasha star meglumines are added, insulated and stirred 60min, De Lasha star meglumine is not completely dissolved, with dilute salt
Acid or diluted sodium hydroxide solution regulation pH value, are settled to total amount, insulated and stirred 60min, De Lasha star meglumine is completely molten not yet
Solution.
Verify embodiment
Influence factor is tested
By finished product preparation obtained by the embodiment of the present invention 1~7 and comparative example 1-6 be placed in 25 DEG C, RH60% constant temperature it is permanent
In wet tank, appearance character, pH, moisture, the change about material and content before and after sampling in the 0th, 12,24 month is investigated and redissolved
Change, result of the test is shown in Table 1
Result is investigated in the influence factor of table 1 experiment (60 DEG C of high temperature)
Remarks：■ whites to off-white color freezes block；● colourless clear liquid.
★ is 1/3rd filling according to container (cillin bottle) cumulative volume
▲(the containing 500mg in every bottle) identical in quality containing the virtuous husky star meglumine (in terms of De Lasha stars) of drawing in every bottle.
Tested from long-term examination：Embodiment 1~7 and comparative example 1 24 months outer characters, pH, moisture,
It is consistent about indices such as material and contents, significant change does not occur.In the case where drug content is equal, contrast is implemented
Filling amount is big in example 1, and the container cillin bottle used is big, is unfavorable for production and transportation, while add cost.And comparative example
2~5 in solution process for preparation main ingredient can not be completely dissolved.The relevant material of comparative example 6 substantially becomes big.
Claims (10)
1. a kind of injection De Lasha star meglumines, it is characterised in that mainly by active component De Lasha stars meglumine, Portugal's first
Amine, sulfobutyl ether-beta-cyclodextrin, Ergol, pH adjusting agent and water for injection composition.
A kind of 2. injection De Lasha star meglumines as claimed in claim 1, it is characterised in that the De Lasha stars meglumine
Concentration range be 50mg/ml~100mg/ml.
A kind of 3. injection De Lasha star meglumines as claimed in claim 1, it is characterised in that the De Lasha stars meglumine
Mass ratio with sulfobutyl ether-beta-cyclodextrin is that scope is 1:1.2~1:1.6.
A kind of 4. injection De Lasha star meglumines as claimed in claim 3, it is characterised in that the De Lasha stars meglumine
Mass ratio with sulfobutyl ether-beta-cyclodextrin is that scope is 1:1.4.
A kind of 5. injection De Lasha star meglumines as claimed in claim 1, it is characterised in that it is described state Ergol with
The mass ratio of sulfobutyl ether-beta-cyclodextrin is that scope is 1:3~1:2, preferably 1:2.5.
A kind of 6. injection De Lasha star meglumines as claimed in claim 1, it is characterised in that described De Lasha stars Portugal first
The mass ratio of amine (being counted using De Lasha stars) and meglumine is 1:0.1~1:0.5.
7. a kind of injection De Lasha star meglumines as claimed in claim 1, it is characterised in that described pH adjusting agent is salt
One or more of mixed solutions in acid, phosphoric acid, acetic acid or citric acid.
8. a kind of preparation method of injection De Lasha star meglumines as described in claim 1-7 any claims, it is special
Sign is, mainly includes the following steps that：The Ergol of recipe quantity is weighed, addition is cooled to the appropriate water for injection of room temperature in advance
In, stir, add the sulfobutyl ether-beta-cyclodextrin of recipe quantity, heating stirs, and adds recipe quantity De Lasha stars Portugal first
Amine, meglumine, insulated and stirred adjust pH, are settled to total amount, stir to being completely dissolved；Filtering, filling, freeze-drying, mesh
Inspection is got product.
A kind of 9. preparation method of injection De Lasha star meglumines as claimed in claim 8, it is characterised in that described pH
For 7.0~8.0.
10. a kind of preparation method of injection De Lasha star meglumines as claimed in claim 8, it is characterised in that described
PH is 7.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610780347.1A CN107789324B (en) | 2016-08-31 | 2016-08-31 | Delaxacin meglumine for injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610780347.1A CN107789324B (en) | 2016-08-31 | 2016-08-31 | Delaxacin meglumine for injection and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107789324A true CN107789324A (en) | 2018-03-13 |
| CN107789324B CN107789324B (en) | 2021-05-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610780347.1A Active CN107789324B (en) | 2016-08-31 | 2016-08-31 | Delaxacin meglumine for injection and preparation method thereof |
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| Country | Link |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113413389A (en) * | 2021-07-19 | 2021-09-21 | 成都赜灵生物医药科技有限公司 | Preparation of histone deacetylase inhibitor and preparation method and application thereof |
| CN113509476A (en) * | 2021-07-23 | 2021-10-19 | 杭州剂泰医药科技有限责任公司 | Ruideciclovir composition and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010096551A2 (en) * | 2009-02-18 | 2010-08-26 | Rib-X Pharmaceuticals, Inc. | Antimicrobial compositions |
| CN104958296A (en) * | 2008-11-15 | 2015-10-07 | 麦林塔医疗有限公司 | Antimicrobial compositions |
-
2016
- 2016-08-31 CN CN201610780347.1A patent/CN107789324B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104958296A (en) * | 2008-11-15 | 2015-10-07 | 麦林塔医疗有限公司 | Antimicrobial compositions |
| WO2010096551A2 (en) * | 2009-02-18 | 2010-08-26 | Rib-X Pharmaceuticals, Inc. | Antimicrobial compositions |
Non-Patent Citations (1)
| Title |
|---|
| 姚静主编: "《药用辅料应用指南》", 31 August 2011, 中国医药科技出版社 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113413389A (en) * | 2021-07-19 | 2021-09-21 | 成都赜灵生物医药科技有限公司 | Preparation of histone deacetylase inhibitor and preparation method and application thereof |
| CN113413389B (en) * | 2021-07-19 | 2024-03-15 | 成都赜灵生物医药科技有限公司 | Preparation of histone deacetylase inhibitor, preparation method and application thereof |
| CN113509476A (en) * | 2021-07-23 | 2021-10-19 | 杭州剂泰医药科技有限责任公司 | Ruideciclovir composition and application thereof |
| CN113509476B (en) * | 2021-07-23 | 2023-01-13 | 杭州剂泰医药科技有限责任公司 | Ruideciclovir composition and application thereof |
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| CN107789324B (en) | 2021-05-25 |
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