CN102058890B - Sustained release medicinal auxiliary material for improving stability of basic remedy - Google Patents
Sustained release medicinal auxiliary material for improving stability of basic remedy Download PDFInfo
- Publication number
- CN102058890B CN102058890B CN201010577739.0A CN201010577739A CN102058890B CN 102058890 B CN102058890 B CN 102058890B CN 201010577739 A CN201010577739 A CN 201010577739A CN 102058890 B CN102058890 B CN 102058890B
- Authority
- CN
- China
- Prior art keywords
- arginine
- alpha
- ketoglutarate
- auxiliary material
- sustained release
- 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.)
- Active
Links
Abstract
The invention discloses an auxiliary material capable of being applied to medicament production, which can significantly improve the stability of a basic remedy, prolong the storage life of medicaments, and simultaneously play a role in sustained release. The auxiliary material is L-arginine-alpha-ketoglutarate, wherein L-arginine and alpha-ketoglutaric acid are prepared into a salt according to a mole ratio of 2:1, and the weight ratio of the L-arginine-alpha-ketoglutarate added into a medicament to the basic remedy is 10:1-50:1.
Description
Technical field
The present invention relates to a kind of pharmaceutic adjuvant, relate to specifically a kind of pharmaceutic adjuvant that can improve principal agent stability, slow controlled-release effect is provided.
Background technology
L-arginine-alpha-ketoglutarate, English name is L-Arginine-alpha-Ketoglutarate, and English is called for short AAKG, is different from the crystalline mixture of L-arginine and α-ketoglutaric acid, and there is not sat linkage between the two in common mixt.L-arginine-alpha-ketoglutarate is white or light yellow crystal, and soluble in water, HCl and NaOH solution, be slightly soluble in ethanol, is insoluble to acetone, ether etc.
L-arginine-alpha-ketoglutarate is a kind of amidates health product that on current international market, sales volume increases day by day, as functional nutrient hardening agent and liver-protecting medicine, be mainly used in physique and strengthen tonic, promote rapid growth and the recovery of muscle, promote the absorption of hepatocyte to nutrition and energy, safeguard that liver function normally waits effect.Its major physiological mechanism is that L-arginine-alpha-ketoglutarate can promote nitric oxide production level in a short time, promotes and expansion muscular movement, and then promotes rapid growth and the recovery of muscle, gains in strength and energy.
Zoopery shows, supplementary AAKG can increase the level of arginine and glutamine in skeletal muscle, plays the effect of stimulating immune system function simultaneously.A research for the supplementary AAKG (15g/d) of child also shows, level, promotion that AAKG can promote synthetic auxin comprise the amino acid metabolisms such as insulin like growth factor (IGF1), glutamine and glutamate, Glu, supplement after 5 months and improve significantly in rate of rise.Equally, AAKG can promote the secretion of auxin and the insulin of postoperative patient, and its mesostate glutamine and proline also can promote that wound heals again.In the research for AKG Anticatabolism, there is Metabolism and hypermetabolic 14 multiple trauma patients have participated in experiment, give AAKG 20g tested group of every day, demonstrate aspect the blood level of the free amino acids such as protein conversion, insulin, auxin and glutamine, proline, arginine, obtain equally the highest significantly.Research for healthy male shows in addition, gives the AAKG dosage of 10g every day, and its insulin level raises 20～30%, and supplement separately in the research group of arginine or α-ketoglutaric acid, does not observe this rising.Cell in vitro is cultivated and is shown, AAKG can significantly induce the growth of human fibroblasts, and this cell is similar to muscle fiber cell, and its effect has significant dose-effect relationship, and corresponding single arginine or α-ketoglutaric acid do not have this specific character.
L-arginine-alpha-ketoglutarate, in aqueous solution, can dissociate and form arginine and α-ketoglutaric acid, thereby also can be used as α-ketoglutaric acid or arginic donor, under certain conditions, as the succedaneum of arginine or α-ketoglutaric acid, applies.Arginine is the important source material of the conditionally essential amino acid that can not lack in human body and synthetic protein, creatine, is the important mesostate of organism ornithine cycle, is also nitric oxide production lead.And α-ketoglutaric acid has very strong regulating and controlling effect to the metabolism of protein, and be important substance and the production capacity carrier that promotes tricarboxylic acid cycle.(US Patent No. P 7645742; USP 6905707; USP 7645742)
In existing document, have no L-arginine-alpha-ketoglutarate as the controlled slowly releasing adjuncts application that improves principal agent stability.
Summary of the invention
The object of this invention is to provide a kind of adjuvant that can be applicable to pharmaceutical production, can significantly improve the stability of principal agent, the pot-life of prolong drug, can play the effect of delaying controlled release simultaneously.
The object of the present invention is achieved like this: this adjuvant is L-arginine-alpha-ketoglutarate, wherein (preparation method is shown in Chinese patent 200710063477.4 with the mol ratio proportioning salify of 2: 1 for L-arginine and α-ketoglutaric acid, 200710063478.9,200710063479.3, CN101591271A).Joining L-arginine-alpha-ketoglutarate amount in medicine and the weight ratio of principal agent is 10: 1～50: 1.
The present invention has following features:
1,, under identical storage requirement, the medicine that adds the medicine of this adjuvant and do not add this adjuvant, after depositing same time, obviously reduces palliating degradation degree;
2, add the medicine of this adjuvant to compare with the medicine that does not add this adjuvant, more can resist pH value and change the impact on principal agent composition;
3, the drug release that adds this adjuvant has good uniformity, and can effectively control the slow release behavior of medicine.
Accompanying drawing explanation
Fig. 1: GLP-1 powder injection raw medicine liquid chromatogram
Fig. 2: the GLP-1 injectable powder that adds L-arginine-alpha-ketoglutarate adjuvant is stored 12 months HPLC mensuration drug contents
Fig. 3: the GLP-1 injectable powder that does not add L-arginine-alpha-ketoglutarate adjuvant is stored 12 months HPLC mensuration drug contents
Fig. 4: the GLP-1 injectable powder pH that adds L-arginine-alpha-ketoglutarate adjuvant changes HPLC and measures drug content
Fig. 5: the GLP-1 injectable powder pH that does not add L-arginine-alpha-ketoglutarate adjuvant changes HPLC and measures drug content
The specific embodiment
Below will by instantiation, the invention will be further described:
Example one
Crude drug GLP-1 (GLP-1) is made to aseptic aqueous solution, be divided into two parts, a copy of it adds L-arginine-alpha-ketoglutarate (L-arginine and α-ketoglutaric acid are with the mol ratio proportioning salify of 2: 1) as trial target, addition and principal agent weight ratio are 10: 1, after dissolving completely, carry out routinely sterile filling, after lyophilization, in sealed under aseptic conditions, make; Another part in contrast product is directly carried out sterile filling routinely, and all the other operations are all identical with trial target.Place after 12 months, measure respectively its drug content, high-efficient liquid phasor is shown in Fig. 2, Fig. 3.Fig. 2 compares with crude drug liquid chromatogram, and appearance time and peak area are almost identical, and 12min only has a main peak, has no other impurity peaks; In Fig. 3, before the main peak of 12min, there is a little acromion in 11min, and GLP-1 decomposes.Visible L-arginine-alpha-ketoglutarate can improve principal agent stability as adjuvant, makes it keep the longer time not decompose.
Example two
Crude drug GLP-1 (GLP-1) is made to aseptic aqueous solution, be divided into two parts, a copy of it adds L-arginine-alpha-ketoglutarate (L-arginine and α-ketoglutaric acid are with the mol ratio proportioning salify of 2: 1) as trial target, addition and principal agent weight ratio are 10: 1, after dissolving completely, carry out routinely sterile filling, after lyophilization, in sealed under aseptic conditions, make; Another part in contrast product is directly carried out sterile filling routinely, and all the other operations are all identical with trial target.Trial target and reference substance all dissolve with 5ml water for injection, first with sodium hydroxide solution, adjust pH to 10, mix homogeneously, then adjust pH to 4 with hydrochloric acid solution, and mix homogeneously, its drug content of difference sampling and measuring, result is as shown in Figure 4, Figure 5.Fig. 4 compares with crude drug liquid chromatogram, several unchanged; The visible principal agent of Fig. 5 decomposes completely, and appearance time and peak type all have very large change.Visible L-arginine-alpha-ketoglutarate changes the impact on principal agent as adjuvant available buffer pH.
Example three
By general tablet producing technology, prepare curcumin slow releasing tablet, the weight ratio of L-arginine-alpha-ketoglutarate (L-arginine and α-ketoglutaric acid are with the mol ratio proportioning salify of 2: 1) and raw material curcumin 50: 1, separately add appropriate filler starch, disintegrating agent microcrystalline Cellulose, mix homogeneously, with PVP K3010% (w/v, 80% alcoholic solution) be wetting agent, granulate, the dry rear moderate lubrication agent magnesium stearate of adding, mix homogeneously, tabletting.With reference to appendix XC first method of Chinese Pharmacopoeia version in 2010, measure preparation release behaviour in vitro: 6 of randomization product are placed in respectively the release medium through the deionized water 200ml of ultrasonic degas, in (37 ± 0.5) ℃ constant temperature, slurry method rotating speed is (100 ± 5) rmin
-1, the receiving liquid 2.0ml that gets per hour, filters through microporous filter membrane (0.45 μ m), gets subsequent filtrate as test liquid, and supplements the synthermal release medium of 2.0ml in time, until 8h termination test.The results are shown in following table 1.
The test of table 1 curcumin dissolution of sustained-release tablets
The above results shows, the slow release 8h that this product can be stable discharges good uniformity, can effectively control the slow release behavior of medicine in gastrointestinal tract.
Claims (1)
1. using L-arginine-alpha-ketoglutarate application in preparation GLP-1 injectable powder as the pharmaceutic adjuvant that improves principal agent stability of mol ratio 2:1 salify, it is characterized by, addition and principal agent weight ratio are 10:1.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410677674.5A CN104548107B (en) | 2010-12-08 | 2010-12-08 | A kind of slow controlled release pharmaceutic adjuvant for improving main ingredient stability |
| CN201010577739.0A CN102058890B (en) | 2010-12-08 | 2010-12-08 | Sustained release medicinal auxiliary material for improving stability of basic remedy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010577739.0A CN102058890B (en) | 2010-12-08 | 2010-12-08 | Sustained release medicinal auxiliary material for improving stability of basic remedy |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410677674.5A Division CN104548107B (en) | 2010-12-08 | 2010-12-08 | A kind of slow controlled release pharmaceutic adjuvant for improving main ingredient stability |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102058890A CN102058890A (en) | 2011-05-18 |
| CN102058890B true CN102058890B (en) | 2014-11-12 |
Family
ID=43994513
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010577739.0A Active CN102058890B (en) | 2010-12-08 | 2010-12-08 | Sustained release medicinal auxiliary material for improving stability of basic remedy |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102058890B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101011372A (en) * | 2007-02-02 | 2007-08-08 | 北京和为康医药科技有限公司 | Preparing method of alpha-ketoglutaric acid-arginine salt and its use for treating hepatic disease |
| CN101591271A (en) * | 2008-05-27 | 2009-12-02 | 上海汉飞生化科技有限公司 | A kind of preparation method of crystal L-arginine alpha-ketoglutarate |
-
2010
- 2010-12-08 CN CN201010577739.0A patent/CN102058890B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101011372A (en) * | 2007-02-02 | 2007-08-08 | 北京和为康医药科技有限公司 | Preparing method of alpha-ketoglutaric acid-arginine salt and its use for treating hepatic disease |
| CN101591271A (en) * | 2008-05-27 | 2009-12-02 | 上海汉飞生化科技有限公司 | A kind of preparation method of crystal L-arginine alpha-ketoglutarate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102058890A (en) | 2011-05-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5775464B2 (en) | Delayed release oral dosage composition containing amorphous CDDO-ME | |
| CN103989677A (en) | Use of demethyleneberberine in preparation of blood sugar-reduction drug | |
| CN103919775A (en) | Application of 9-demethylberberine in preparation of hpyerglycemic drug | |
| CN101947234A (en) | Preparation method for preparation containing glucosamine and application thereof | |
| JP7007300B2 (en) | New crystalline form of dapagliflozin and its manufacturing method and application | |
| CN101664384B (en) | N-acetyl-cysteine salt xylitol injection, preparation method and application thereof | |
| CN103110640B (en) | Pharmaceutical composition of injection ceftizoxime sodium and compound amino acid injection | |
| CN102058890B (en) | Sustained release medicinal auxiliary material for improving stability of basic remedy | |
| CN103073617B (en) | N-(2)-L-alanyl-L-glutamine compound | |
| CN104042645B (en) | Compound amino acid injection | |
| CN104548107B (en) | A kind of slow controlled release pharmaceutic adjuvant for improving main ingredient stability | |
| CN102961397B (en) | Pharmaceutical composition of fat emulsion injection and compound amino acid injection | |
| CN109260205B (en) | Application of tetrandrine in preparation of medicine for resisting diabetes and hypertension | |
| CN102210868A (en) | Application of tetrahydropyrimidine and derivatives thereof in preparing oral absorption enhancers | |
| CN102008461B (en) | A kind of ibuprofen drug composite for injection | |
| CN105582546A (en) | Compound enteric-coated tablets of entecavir phospholipid complex and diammonium glycyrrhizinate | |
| CN101822648A (en) | Preparation method and application of nano dobesilate calcium capsule or tablet | |
| WO2019119445A1 (en) | Nadh compound, and formulation and application thereof | |
| CN114053282B (en) | Application of tormentic acid and anisodamine capsules in preparation of medicine for treating diabetes | |
| CN103638020A (en) | Novel pharmaceutical composition for treating gout | |
| CN102757471A (en) | Novel active cytidine disodium triphosphate compound and pharmaceutical composition thereof | |
| CN106074398A (en) | A kind of freeze dried lentinan holoside powder injecta and preparation method thereof | |
| JP2010265186A (en) | Anemia-preventing composition | |
| CN105726508B (en) | Novel Stibene-glucoside sustained-release preparation and preparation method thereof | |
| CN101099741A (en) | Alprostadil and vitamin F millimicroball composite medicine and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20110518 Assignee: Chengdu Yong'an Pharmaceutical Co., Ltd. Assignor: Jiangnan University Contract record no.: 2015510000019 Denomination of invention: Sustained release medicinal auxiliary material for improving stability of basic remedy Granted publication date: 20141112 License type: Exclusive License Record date: 20150324 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model |