CN105796511B - A kind of aceglutamide for Injection composition and preparation method thereof - Google Patents
A kind of aceglutamide for Injection composition and preparation method thereof Download PDFInfo
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- CN105796511B CN105796511B CN201610177247.XA CN201610177247A CN105796511B CN 105796511 B CN105796511 B CN 105796511B CN 201610177247 A CN201610177247 A CN 201610177247A CN 105796511 B CN105796511 B CN 105796511B
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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
- 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, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
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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
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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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of Aceglutamide power for injection preparation, by the parts by weight of aceglutamide 1 10,0.5 20 parts by weight freeze drying protectants and appropriate pH adjusting agent composition, the wherein preferred mannitol of freeze drying protectant: dextran: the combination that sucrose is 1: 1: 1.
Description
Technical field
The present invention relates to a kind of aceglutamide pharmaceutical composition, and in particular to aceglutamide for Injection lyophilized formulations,
Belong to field of medicaments.
Background technology
Aceglutamide, also known as Aceglutamide or NAQ Aceglutamide, chemical name is：N- acetyl-L- glutamy
Amine, its physicochemical property is：White crystalline powder, odorless is tasteless, soluble in water, is slightly soluble in ethanol.
Aceglutamide belongs to central nervous system stimulant, directly can enter central nervous system by blood-brain barrier,
The information transmission of central nervous system is participated in, improves neuron metabolism, cell viability is improved, neural stress ability is maintained, changes
Kind brain function.
It is current further study show that, aceglutamide is as the nutritional support in the training recovery process of high intensity
Thing.Aceglutamide promotes amino acid transport, strengthens glutathion inside cell and DNA synthesis.
At present, the common formulations of aceglutamide are injection, including：Powder-injection, parenteral solution.
Prior art CN1830425A discloses a kind of preparation method of acetyl glutamine injection, is needed in preparation strict
Control the technological parameters such as pH value, temperature, concentration, ionic strength.In addition, being the purity of the decoction obtained by increase, in ultrafiltrate
, it is necessary to be purified using a certain amount of activated carbon after being mixed with Calcium Disodium Versenate solution.
Prior art CN1535678A discloses the Aceglutamide power for injection preparation and its preparation technology of a kind of stabilization,
Said preparation is made up of aceglutamide, freeze drying protectant and PH conditioning agents.Due to aceglutamide acetyl group in aqueous
Easily it is decomposed and causes content to decline.
It is above-mentioned in the prior art, be required in the preparation technology of aceglutamide the pH value of strict control solution, reaction or
The technological parameters such as dry temperature, so as to improve the stability of preparation, meet clinical practice requirement.But to the strict of technological parameter
Control not only increases running cost, and the reappearance of operating process is poor, so that the above method can not be industrialized
Production, limits the practical application of aceglutamide preparation.
Additionally, it is well known that, need to use activated carbon to be decolourized in injection preparation process, disclosed in above-mentioned each document
Method in, activated carbon is respectively provided with certain suction-operated to aceglutamide, so as to reduce the yield of aceglutamide, carries
High pharmacy cost.
The present inventor passes through the discovery that studies for a long period of time, the aceglutamide composition of the proportioning of special component, in set-up procedure
In the aceglutamide compound be hardly tightly held by activated carbon, and property is stable, is difficult to be hydrolyzed and aoxidizes, influence production
Product quality and curative effect, the yield so as to improve preparation technology, have saved preparation cost.
Crucially, the aceglutamide composition of the present invention matched using special component, is had at antifatigue aspect and expected
Less than technique effect.
The content of the invention
It is therefore an object of the present invention to provide a kind of aceglutamide composition, it has good stability, and has
There is significant anti-fatigue effect.
An object of the present invention is there is provided a kind of Aceglutamide power for injection preparation, by aceglutamide, frozen-dried protective
Agent and PH conditioning agents are made.
Wherein, freeze drying powder injection of the present invention is by aceglutamide 1-10 parts by weight, 0.5-20 parts by weight freeze drying protectants
Constituted with appropriate pH adjusting agent.
Freeze drying powder injection of the present invention is further preferably by aceglutamide 2-8 parts by weight, 6-15 parts by weight frozen-dried protectives
Agent and appropriate PH conditioning agents composition.
Freeze drying powder injection of the present invention is most preferably by the parts by weight of aceglutamide 5,10-12 parts by weight freeze drying protectant and appropriate
PH adjusting agent composition.
Freeze drying protectant of the present invention can be using the conventional various protective agents in this area, it is preferred to use mannitol：Dextrose
Acid anhydride：The composition that sucrose is 1: 1: 1.
PH conditioning agents of the present invention can be using the conventional pharmaceutically acceptable pH adjusting agent in this area, preferably sodium hydroxide.
As one of preferred embodiment of the invention, freeze drying powder injection of the present invention is most preferably by the weight of aceglutamide 5
Part, 4 portions of mannitol, 4 parts of dextrans, 4 portions of sucrose and appropriate pH adjusting agent composition.
An object of the present invention is including following there is provided a kind of preparation method of Aceglutamide power for injection preparation
Step：
(1) aceglutamide of recipe quantity is taken, is added water appropriate, after stirring evenly, dissolving is adjusted to 10% sodium hydroxide, and adjust pH
Then value adds mannitol, dextran and sucrose stirring and dissolving to 5.6, and the needle-use activated carbon for adding the amount of volume 0.1% is normal
Warm stirring and adsorbing 20 minutes, filtering decarbonization；
(2) filtrate mends water for injection to 2000ml, crosses 0.22 μm of miillpore filter, determines intermediates content, it is qualified after, it is filling
In 7ml cillin bottles, every 2ml.
(3) canned sample half plus butyl rubber bung, sabot are inserted in freeze drier, are freeze-dried.
It is further preferred that the step of freeze drying is：
Canned sample half plus butyl rubber bung, sabot are inserted in freeze drier, are freeze-dried, are cooled to -40
DEG C, after being incubated 2 hours, by about 1 DEG C/h of heating, -5 DEG C~0 DEG C lyophilization is to slowly warm up to, then be warming up to after 35 DEG C, protect
Temperature 5 hours.
There is provided Aceglutamide power for injection preparation reduction serum BUN purposes for another object of the present invention.
There is provided the antifatigue effect of Aceglutamide power for injection preparation for another object of the present invention.
Embodiment
Following examples are that the present invention is further illustrated, but are never limited the scope of the present invention.Referring to
Embodiment is further elaborated on the present invention, it should be appreciated to those skilled in the art that the present invention is not limited to these implementations
Example and the preparation method used.Moreover, those skilled in the art can be equal according to description of the invention to the present invention
Replace, combine, improve or modify, but these are intended to be included in the scope of the present invention.
Embodiment 1
The aceglutamide of recipe quantity is taken, is added water appropriate, after stirring evenly, dissolving is adjusted to 10% sodium hydroxide, and adjust pH value
To 5.6, mannitol, dextran and sucrose stirring and dissolving are then added, the needle-use activated carbon normal temperature of the amount of volume 0.1% is added
Stirring and adsorbing 20 minutes, filtering decarbonization；Filtrate mends water for injection to 2000ml, crosses 0.22 μm of miillpore filter, determines intermediate and contains
Amount, it is qualified after, filling in 7ml cillin bottles, every 2ml.
Canned sample half plus butyl rubber bung, sabot are inserted in freeze drier, are freeze-dried, are cooled to -40
DEG C, after being incubated 2 hours, by about 1 DEG C/h of heating, -5 DEG C~0 DEG C lyophilization is to slowly warm up to, then be warming up to after 35 DEG C, protect
Temperature 5 hours.
Comparative example 1
The preparation method and step of freeze drying are carried out with reference to embodiment 1.
Comparative example 2
The preparation method and step of freeze drying are carried out with reference to embodiment 1.
Comparative example 3
The preparation method and step of freeze drying are carried out with reference to embodiment 1.
Comparative example 4
The preparation method and step of freeze drying are carried out with reference to embodiment 1.
Test example 1
For comparing under the same terms, needle-use activated carbon is to acetyl paddy in aceglutamide composition of the present invention and reference examples
Amide compositions adsorb situation.
In embodiment 1 and the preparation process of comparative example 1-4 sample, filtering decarbonization it, determine in above-mentioned each solution
Aceglutamide content, and investigate the clarity of solution, the results are shown in Table 1.
Table 1
As can be seen from the above table, under using identical process conditions, above-mentioned 5 samples can make the solution after absorption clear
Lightness, which is met, to be required, but needle-use activated carbon is significantly lower than comparative example 1-4 to the adsorption rate of the sample of embodiment 1.It can be seen that, the present invention
Aceglutamide in composition obtained by embodiment is difficult to be adsorbed by needle-use activated carbon, therefore, it is possible to improve preparation medicine group
Yield during compound.
Test example 2
Mouse blood urea nitrogen (BUN) influence experiment
Experimental animal is originated and chooses healthy adult Kunming mouse 100 with packet, and body weight 18-22g, male and female are not limited.With
Machine is divided into 5 groups (1 group of embodiment, comparative example 1-4 groups), every group 20.1 group of embodiment injects corresponding respectively with comparative example 1-4 groups
Aceglutamide sample 200mg/ (kgd).Every group of continuous use 21 days.After last dose 0.5 hour, swimming pool middle reaches are put into
Swim (water temperature (30 ± 2.0) DEG C), taken out after 90min, eyeball of mouse blood sampling is won immediately, serum is centrifuged, BUN contents are determined.
Influence of the aceglutamide of table 2 to mouse BUN
| Group | BUN contents (mmol/L) |
| Embodiment 1 | 6.81±1.56 |
| Comparative example 1 | 9.22±1.20 |
| Comparative example 2 | 8.76±1.51 |
| Comparative example 3 | 8.98±1.42 |
| Comparative example 4 | 9.01±1.23 |
Conclusion：Serum BUN indexs are to reflect organism fatigue degree and the important indicator of functional condition, and BUN content is random
The increase of body exercise load and increase, body load adaptability is poorer, BUN increase it is more obvious.
The aceglutamide that 1 group of embodiment more substantially reduces the content of BUN after motion compared with comparative example 1-4 groups, it was demonstrated that the group
Compound has unexpected technique effect at antifatigue aspect.
Claims (3)
1. a kind of Aceglutamide power for injection preparation, it is characterised in that by 5 parts of the aceglutamide based on parts by weight, 4 parts it is sweet
Dew alcohol, 4 parts of dextrans, 4 portions of sucrose and appropriate pH adjusting agent are made, and wherein freeze drying protectant is mannitol: dextran:
The combination that sucrose is 1: 1: 1, its preparation method comprises the following steps：
(1) aceglutamide of recipe quantity is taken, is added water appropriate, after stirring evenly, dissolving is adjusted to 10% sodium hydroxide, and adjust pH value extremely
5.6, mannitol, dextran and sucrose stirring and dissolving are then added, the needle-use activated carbon normal temperature for adding the amount of volume 0.1% is stirred
Mix absorption 20 minutes, filtering decarbonization；
(2) filtrate mends water for injection to 2000ml, crosses 0.22 μm of miillpore filter, determines intermediates content, it is qualified after, it is filling in
In 7ml cillin bottles, every 2ml；
(3) canned sample half plus butyl rubber bung, sabot are inserted in freeze drier, are freeze-dried.
2. use of a kind of Aceglutamide power for injection preparation in the medicine for preparing reduction serum BUN described in claim 1
On the way.
3. purposes of a kind of Aceglutamide power for injection preparation in antifatigue medicine is prepared described in claim 1.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610177247.XA CN105796511B (en) | 2016-03-28 | 2016-03-28 | A kind of aceglutamide for Injection composition and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610177247.XA CN105796511B (en) | 2016-03-28 | 2016-03-28 | A kind of aceglutamide for Injection composition and preparation method thereof |
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| Publication Number | Publication Date |
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| CN105796511A CN105796511A (en) | 2016-07-27 |
| CN105796511B true CN105796511B (en) | 2017-08-29 |
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| CN112168789B (en) * | 2020-09-25 | 2022-08-16 | 广州一品红制药有限公司 | Acetyl glutamine medicine composition containing amino acid for injection and application thereof |
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| CN104434819B (en) * | 2014-11-15 | 2018-06-01 | 成都天台山制药有限公司 | Aceglutamide for Injection powder-injection pharmaceutical composition and preparation method |
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Effective date of registration: 20221202 Address after: No.6 Dongbo Road, East District, Guangzhou Economic and Technological Development Zone, Guangdong 510000 Patentee after: GUANGZHOU YIPINHONG PHARMACEUTICAL Co.,Ltd. Patentee after: GUANGDONG ZERUI PHARMACEUTICAL Co.,Ltd. Patentee after: Guangzhou Lianrui Pharmaceutical Co.,Ltd. Patentee after: Guangzhou Runlin Pharmaceutical Technology Co.,Ltd. Patentee after: Euphorbia Biological Medicine Co.,Ltd. Address before: No. 6, Dongbo Road, Guangzhou Economic and Technological Development Zone, Guangdong 510760 Patentee before: GUANGZHOU YIPINHONG PHARMACEUTICAL Co.,Ltd. |