CN104069072B - A kind of L-084 composition granule - Google Patents
A kind of L-084 composition granule Download PDFInfo
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- CN104069072B CN104069072B CN201410319910.6A CN201410319910A CN104069072B CN 104069072 B CN104069072 B CN 104069072B CN 201410319910 A CN201410319910 A CN 201410319910A CN 104069072 B CN104069072 B CN 104069072B
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- 0 C[C@]([C@@]([C@@]([C@]1C)N2C(C(OCOC(C(C)(C)C)=*)=O)=C1SC(C1)CN1C1=NCCS1)C2=O)O Chemical compound C[C@]([C@@]([C@@]([C@]1C)N2C(C(OCOC(C(C)(C)C)=*)=O)=C1SC(C1)CN1C1=NCCS1)C2=O)O 0.000 description 1
Abstract
The present invention relates to the field of chemical synthesis, disclose a kind of L-084 composition granule.Granule of the present invention in parts by weight, is made up of the L-084 of drug ingedient 40 weight portion, the sucrose of 198.7 219.7 weight portions, 5 10 weight portion HEMCs, 36 weight portion Ac-Di-Sols, 25 weight portion phosphatidyl-ethanolamines, 10 20 weight portion inositols, 0.1 0.2 weight portion sodium ascorbate palmitates and 0.2 0.5 weight portion aspartames.Granule of the present invention uses the multiple suitable drugs composition including L-084 to prepare a kind of new granule, prepared granule all shows the effect higher than existing patented product in accelerated test, long term test and fungistatic effect are tested, there is the highest quality, it is possible to be widely used in clinical treatment.
Description
Technical field
The present invention relates to field of medicine preparations, be specifically related to a kind of L-084 composition granule.
Background technology
L-084, chemistry entitled (+)-(4R, 5S, 6S)-6-[(1R)-hydroxyethyl]-4-methyl-7-oxygen
Generation-3 [[1-(2-thiazoline-2-base)-3-azetidinyl] sulphur]-1-azabicyclo [3.2.0] hept-2-ene"-2-formic acid
(2,2-dimethyl-1-oxopropoxy) methyl esters, belongs to carbapenem antibiotic, and structural formula is as follows:
L-084 is researched and developed by Pfizer Inc. the earliest, and L-084 granula subtilis is by day
This Mingzhi company develops, and obtains Japan's approval in February, 2009, and lists in April, 2009, but
Domestic do not have listing producer and relevant report.L-084 granula subtilis is used for pediatric patient ear nose larynx
With the treatment of the infection of the upper respiratory tract, it is first treatment infected for streptococcus pneumonia drug resistance strain, bag
Include the penem-like pharmaceutical of continuation tympanitis and bacterial pneumonia.L-084 has a broad antifungal spectrum, right
The bacterial strain that great majority are clinically separated, tebipenem all shows more higher than penicillin series and cephalo series
Antibiotic property, and compared with the carbapenem antibiotic of other injections, tebipenem also shows same journey
Degree or higher antibacterial effect.Especially for the penicillin resistant causing childhood infection main cause in recent years
Streptococcus pneumonia, resistance to erythromycin streptococcus pneumonia and haemophilus influenzae show extremely strong antibacterial effect.
Due to L-084 less stable, there is related substance increase very big under the conditions of hot and humid,
So the selection of drug ingedient and consumption become particularly important, drug ingedient chooses at random and makes it possible to replace
Than training south volt ester granule dissolution rate be deteriorated, have related substance increase, content reduce, polymer increase,
Moisture risings etc., even cannot granulating.The Chinese patent of Application No. 201310493646.3 is open
A kind of L-084 composition granule, its with L-084, pregelatinized starch,
Mannitol, sucrose and stevioside are that component is made, although the long term test of this patent notes and accelerated test
Result shows that this granule has certain quality, but in terms of L-084 granule quality,
Still need to be improved further.Meanwhile, the selection of drug ingedient also contributes to the antibacterial of L-084
Effect, how by selecting appropriate drug ingedient to make a kind of stability and fungistatic effect higher than existing product
The L-084 granule of product is the research emphasis of medicine research staff.
Summary of the invention
In view of this, it is an object of the invention to provide a kind of L-084 composition granule,
Described granule is made to have higher stability in extreme circumstances；
A kind of L-084 composition granule of offer is provided so that
The fungistatic effect of described granule is improved.
For achieving the above object, the present invention provides following technical scheme:
A kind of L-084 composition granule, in parts by weight, by drug ingedient 40 weight portion
L-084, the sucrose of 198.7-219.7 weight portion, 5-10 weight portion hydroxyethyl methyl fiber
Element, 3-6 weight portion Ac-Di-Sol, 2-5 weight portion phosphatidyl-ethanolamine, 10-20 weight portion
Inositol, 0.1-0.2 weight portion sodium ascorbate palmitate and 0.2-0.5 weight portion aspartame composition.
Present invention applicant furthers investigate the physicochemical property of L-084, stability feature and particle
Agent formulation characteristic, selects suitable drug ingedient to work in coordination with L-084 according to these features and makes newly
Type granule.
Wherein, as preferably, granule of the present invention in parts by weight, by 40 weight portions for than training
South volt ester, the sucrose of 209 weight portions, 7.5 weight portion HEMCs, 4.5 weight portion crosslinkings
Sodium carboxymethylcellulose, 3.5 weight portion phosphatidyl-ethanolamines, 15 weight portion inositols, 0.15 weight portion are anti-bad
Hematic acid sodium palmitate and 0.35 weight portion aspartame composition.
As preferably, granule of the present invention is prepared by dry granulation, it is further preferred that described
Dry granulation particularly as follows:
Pulverize drug ingedient L-084, sucrose, HEMC, crosslinking carboxylic respectively
Sodium carboxymethylcellulose pyce, phosphatidyl-ethanolamine, inositol, sodium ascorbate palmitate and aspartame, mixed
Close uniformly to send in dry granulating machine and pelletize, then sieve, it is thus achieved that L-084 granule.
As preferably, the ambient humidity of described dry granulation is below 60%.
As preferably, the powder particle diameter of described each drug ingedient is 80 mesh.
As preferably, described dry granulating machine uses 16 mesh mesh screens.
As preferably, described screening be with shaking screen screen out the fine uniform between 16 mesh and 60 mesh,
Particle without bulk.
Accelerated test and the long-term test results of granule of the present invention show, at the total impurities in same stage
On content all less than the patent of Application No. 201310493646.3, there is significant difference.Meanwhile, exist
In the detection of antibacterial activity, the antibacterial effect of granule of the present invention is improved, its MIC50And MIC90
(minimum inhibitory concentration of suppression 50% and 90% bacterial strain) is below 201310493646.3 patent notes
Data.
From above technical scheme, granule of the present invention uses including L-084
Multiple suitable drugs composition prepare a kind of new granule, prepared granule accelerated test,
Long term test and fungistatic effect test all show the effect higher than existing patented product, has the highest
Quality, it is possible to be widely used in clinical treatment.
Detailed description of the invention
The invention discloses a kind of L-084 composition granule, those skilled in the art are permissible
Use for reference present disclosure, be suitably modified technological parameter and realize.Special needs to be pointed out is, all similar replacing
Changing and change apparent to those skilled in the art, they are considered as being included in the present invention.
Product of the present invention is described by preferred embodiment, related personnel substantially can without departing from
In present invention, spirit and scope, compound as herein described and preparation method are modified or suitable
When change and combination, realize and apply the technology of the present invention.
Below in conjunction with embodiment, the present invention is expanded on further.
Embodiment 1: prepare L-084 composition granule of the present invention
Respectively pulverize the L-084 of drug ingedient 40 weight portion, the sucrose of 209 weight portions, 7.5
Weight portion HEMC, 4.5 weight portion Ac-Di-Sols, 3.5 weight portion phosphatide
Acyl monoethanolamine, 15 weight portion inositols, 0.15 weight portion sodium ascorbate palmitate, 0.35 weight portion Ah
Department's handkerchief material, mixes in feeding dry granulating machine and pelletizes；
Dry granulation process step:
In the environment of relative humidity is less than 60%, above-mentioned supplementary material was pulverized 80 mesh sieves, by former auxiliary
Expecting to mix in SYH-15 three-dimensional mixer, then putting pelletizes in GL-5 dry granulating machine (is furnished with
16 mesh mesh screens), screen out the fine uniform between 16 mesh and 60 mesh, particle without bulk with shaking screen,
Then carry out intermediate detection, particle detection level and moisture, be sub-packed in aluminium by standard compliant by specification
Mould in compound membrane bag, seal, pack, Quan Jian, storage.
Embodiment 2: prepare L-084 composition granule of the present invention
Respectively pulverize the L-084 of drug ingedient 40 weight portion, the sucrose of 219.7 weight portions, 5
Weight portion HEMC, 3 weight portion Ac-Di-Sols, 2 weight portion phosphatidyl second
Hydramine, 10 weight portion inositols, 0.1 weight portion sodium ascorbate palmitate, 0.2 weight portion aspartame
Material, mixes in feeding dry granulating machine and pelletizes；
Dry granulation process step:
In the environment of relative humidity is less than 60%, above-mentioned supplementary material was pulverized 80 mesh sieves, by former auxiliary
Expecting to mix in SYH-15 three-dimensional mixer, then putting pelletizes in GL-5 dry granulating machine (is furnished with
16 mesh mesh screens), screen out the fine uniform between 16 mesh and 60 mesh, particle without bulk with shaking screen.
Then carry out intermediate detection, particle detection level and moisture, be sub-packed in aluminium by standard compliant by specification
Mould in compound membrane bag, seal, pack, Quan Jian, storage.
Embodiment 3: prepare L-084 composition granule of the present invention
Respectively pulverize the L-084 of drug ingedient 40 weight portion, the sucrose of 198.7 weight portions,
10 weight portion HEMCs, 6 weight portion Ac-Di-Sols, 5 weight portion phosphatidyls
Monoethanolamine, 20 weight portion inositols, 0.2 weight portion sodium ascorbate palmitate, 0.5 weight portion A Sipa
Smooth material, mixes in feeding dry granulating machine and pelletizes；
Dry granulation process step:
In the environment of relative humidity is less than 60%, above-mentioned supplementary material was pulverized 80 mesh sieves, by former auxiliary
Expecting to mix in SYH-15 three-dimensional mixer, then putting pelletizes in GL-5 dry granulating machine (is furnished with
16 mesh mesh screens), screen out the fine uniform between 16 mesh and 60 mesh, particle without bulk with shaking screen,
Then carry out intermediate detection, particle detection level and moisture, be sub-packed in aluminium by standard compliant by specification
Mould in compound membrane bag, seal, pack, Quan Jian, storage.
Embodiment 4: accelerated test
The L-084 composition granule embodiment of the present invention 1 prepared is according to Chinese Pharmacopoeia
Within 2005, version medicine stability test knows the relevant regulations of principle, temperature be 40 DEG C ± 2 DEG C, relatively
Being accelerated test under conditions of humidity 75% ± 5%, the time is 6 months, during test respectively at the 1st,
2, sample once 3,6 the end of month, be measured by stability high spot reviews project, the results are shown in Table 1.
Table 1 accelerated test result
With reference to the testing result of upper table, and patent Example 4 table 5 of Application No. 201310493646.3
The Data Comparison recorded, it can be clearly seen that, in terms of impurity content, present invention reduces about 0.15%,
Further improve the stability of product.
Embodiment 5: long term test
The L-084 composition granule embodiment of the present invention 1 prepared is according to Chinese Pharmacopoeia
Within 2005, version medicine stability test knows the relevant regulations of principle, temperature be 25 DEG C ± 2 DEG C, relatively
Being accelerated test under conditions of humidity 60% ± 10%, the time is 36 months, respectively at the during test
0, sample once 3,6,9,12,18,24,36 the end of month, carry out by stability high spot reviews project
Measure, the results are shown in Table 2.
Table 2 long-term test results
With reference to the testing result of upper table, and patent Example 4 table 6 of Application No. 201310493646.3
The Data Comparison recorded, it can be clearly seen that, in terms of impurity content, present invention reduces about 0.15%,
Further improve the stability of product.
Embodiment 6: fungistatic effect is tested
Agar dilution is used to measure the embodiment of the present invention 1 L-084 composition granule
Low Mlc, inoculates with multiple spot dibbler, and each o'clock containing about 104CFU, cultivates 24h, result for 37 DEG C
It is shown in Table 3.
Table 3 fungistatic effect is tested
As seen from the above table, L-084 composition granule of the present invention is the most auxiliary owing to selecting
Material, can play the fungistatic effect of L-084 to greatest extent, and compare granule (data
Patent Example 3 with reference to Application No. 201310493646.3 is recorded) then apparently higher than the present invention's
MIC50And MIC90, fungistatic effect is not so good as granule of the present invention.
The above is only the preferred embodiment of the present invention, it is noted that general for the art
For logical technical staff, under the premise without departing from the principles of the invention, it is also possible to make some improvement and profit
Decorations, these improvements and modifications also should be regarded as protection scope of the present invention.
Claims (8)
1. a L-084 composition granule, it is characterised in that in parts by weight, by medicine
The L-084 of thing composition 40 weight portion, the sucrose of 198.7-219.7 weight portion, 5-10 weight portion
HEMC, 3-6 weight portion Ac-Di-Sol, 2-5 weight portion phosphatidyl ethanol
Amine, 10-20 weight portion inositol, 0.1-0.2 weight portion ascorbyl palmitate and 0.2-0.5 weight portion Ah
Si Patan forms.
The most according to claim 1, granule, it is characterised in that in parts by weight, by drug ingedient
The L-084 of 40 weight portions, the sucrose of 209 weight portions, 7.5 weight portion hydroxyethyl methyl fibers
Element, 4.5 weight portion Ac-Di-Sols, 3.5 weight portion phosphatidyl-ethanolamines, 15 weight portion fleshes
Alcohol, 0.15 weight portion ascorbyl palmitate and 0.35 weight portion aspartame composition.
Granule the most according to claim 1, it is characterised in that prepared by dry granulation.
Granule the most according to claim 3, it is characterised in that described dry granulation particularly as follows:
Pulverize drug ingedient L-084, sucrose, HEMC, crosslinking carboxylic respectively
Sodium carboxymethylcellulose pyce, phosphatidyl-ethanolamine, inositol, ascorbyl palmitate and aspartame, mixing
Uniformly send in dry granulating machine and pelletize, then sieve, it is thus achieved that L-084 granule.
Granule the most according to claim 4, it is characterised in that the ambient humidity of described dry granulation
Below 60%.
Granule the most according to claim 4, it is characterised in that the pulverizing grain of described each drug ingedient
Footpath is 80 mesh.
Granule the most according to claim 4, it is characterised in that described dry granulating machine uses 16
Mesh mesh screen.
Granule the most according to claim 4, it is characterised in that described screening is for sieve with shaking screen
Go out the fine uniform between 16 mesh and 60 mesh, particle without bulk.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410319910.6A CN104069072B (en) | 2014-07-07 | 2014-07-07 | A kind of L-084 composition granule |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410319910.6A CN104069072B (en) | 2014-07-07 | 2014-07-07 | A kind of L-084 composition granule |
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| Publication Number | Publication Date |
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| CN104069072A CN104069072A (en) | 2014-10-01 |
| CN104069072B true CN104069072B (en) | 2016-09-07 |
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| CN201410319910.6A Active CN104069072B (en) | 2014-07-07 | 2014-07-07 | A kind of L-084 composition granule |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102836130A (en) * | 2012-09-19 | 2012-12-26 | 山东罗欣药业股份有限公司 | Tebipenem pivoxil granules |
| CN102860985A (en) * | 2011-07-06 | 2013-01-09 | 石药集团中奇制药技术（石家庄）有限公司 | Tebipenem pivoxil oral preparation and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004035517A (en) * | 2002-07-08 | 2004-02-05 | Wyeth Lederle Japan Ltd | Carbapenem antibiotic-containing oral preparation |
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2014
- 2014-07-07 CN CN201410319910.6A patent/CN104069072B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102860985A (en) * | 2011-07-06 | 2013-01-09 | 石药集团中奇制药技术（石家庄）有限公司 | Tebipenem pivoxil oral preparation and preparation method thereof |
| CN102836130A (en) * | 2012-09-19 | 2012-12-26 | 山东罗欣药业股份有限公司 | Tebipenem pivoxil granules |
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| CN104069072A (en) | 2014-10-01 |
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