CN101961312B - Lipoid acid composition for injection - Google Patents
Lipoid acid composition for injection Download PDFInfo
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- CN101961312B CN101961312B CN201010293789A CN201010293789A CN101961312B CN 101961312 B CN101961312 B CN 101961312B CN 201010293789 A CN201010293789 A CN 201010293789A CN 201010293789 A CN201010293789 A CN 201010293789A CN 101961312 B CN101961312 B CN 101961312B
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- Prior art keywords
- thioctic acid
- methionine
- antioxidant
- compositions
- arginine
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- 239000000203 mixture Substances 0.000 title claims abstract description 42
- 238000002347 injection Methods 0.000 title claims abstract description 29
- 239000007924 injection Substances 0.000 title claims abstract description 29
- 239000002253 acid Substances 0.000 title 1
- 229960002663 thioctic acid Drugs 0.000 claims abstract description 78
- 235000019136 lipoic acid Nutrition 0.000 claims abstract description 70
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims abstract description 30
- 229930182817 methionine Natural products 0.000 claims abstract description 28
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 26
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 24
- 235000006708 antioxidants Nutrition 0.000 claims abstract description 24
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims description 68
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims description 65
- 229960004452 methionine Drugs 0.000 claims description 29
- 239000004475 Arginine Substances 0.000 claims description 24
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 24
- 235000009697 arginine Nutrition 0.000 claims description 24
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 22
- 229960000281 trometamol Drugs 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 claims description 2
- 229930028154 D-arginine Natural products 0.000 claims description 2
- FFEARJCKVFRZRR-SCSAIBSYSA-N D-methionine Chemical compound CSCC[C@@H](N)C(O)=O FFEARJCKVFRZRR-SCSAIBSYSA-N 0.000 claims description 2
- 229930182818 D-methionine Natural products 0.000 claims description 2
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 2
- 229930064664 L-arginine Natural products 0.000 claims description 2
- 235000014852 L-arginine Nutrition 0.000 claims description 2
- 229930195722 L-methionine Natural products 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 abstract 3
- 235000006109 methionine Nutrition 0.000 description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 11
- 230000001954 sterilising effect Effects 0.000 description 11
- 238000004659 sterilization and disinfection Methods 0.000 description 10
- 238000001914 filtration Methods 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 239000012982 microporous membrane Substances 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 8
- 230000000694 effects Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 229960003121 arginine Drugs 0.000 description 5
- 208000019802 Sexually transmitted disease Diseases 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 235000010265 sodium sulphite Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010027439 Metal poisoning Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000019155 Radiation injury Diseases 0.000 description 1
- 241000282894 Sus scrofa domesticus Species 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- -1 diabetes Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000010501 heavy metal poisoning Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 150000002742 methionines Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a lipoic acid composition for injection, which is an injection and comprises the components of lipoic acid, a compatibilizer and an antioxidant. The disclosed lipoic acid composition has high stability by taking methionine as the antioxidant.
Description
Technical field
The present invention relates to a kind of thioctic acid compositions, further is a kind of injection thioctic acid compositions, contains thioctic acid, solubilizing agent, antioxidant, belongs to field of medicaments.
Background technology
Thioctic acid is the natural product of from Hepar Sus domestica, separating, and discovers that it has excellent antioxidant effect in vivo, is described as universal antioxidant.The multinomial in recent years thioctic acid of discovering has prevention and therapeutic effect to the relevant multiple disease of active oxidation free radical such as diabetes, heavy metal poisoning, radiation injury, degeneration neuropathy etc.Diabetes are a kind of comprehensive metabolism disorders, and it is modal chronic diabetic complications that diabetes peripheral nervous sexually transmitted disease (STD) becomes, and has a strong impact on patient's quality of life.Experiment confirm, supplemented with lipoic acid can increase the endoneurium blood flow, increases glutathione concentrations and improves the MNCV of teleneuron, becomes disease thereby effectively improve diabetes peripheral nervous sexually transmitted disease (STD).
Marketed drug thioctic acid the earliest comes from Germany; In recent years domesticly also ratified the listing of multiple imitated thioctic acid injection; Its prescription consists of thioctic acid+trometamol+sodium sulfite or thioctic acid+ethylenediamine+benzyl alcohol, yet above-mentioned prescription can not solve the stability problem of thioctic acid injection effectively; Long-term storage can have the related substance problem that exceeds standard, and influences drug effect and drug safety.
To this problem, there have been some technical schemes to attempt to improve at present both at home and abroad.A kind of thioctic acid injection was disclosed like German patent application EP0318891 in 1992; Thioctic acid is mixed with trometamol and arginine; There is bigger defective in this injection, on the one hand arginine consumption big (need 30% arginine in the unit medicine, calculate with mole); The injection thioctic acid content of unit mole is lower, need increase the injection consumption when causing clinical use; Should increase the stable effect of thioctic acid and unsatisfactory by prescription on the other hand.One Chinese patent application CN200510025601 discloses a kind of thioctic acid freeze-dried powder, and the scheme of employing is with existing injection dosage changing form on the market, and the preparation technology of lyophilized injectable powder compares with injection and wants complicated, and has increased preparation cost.
Therefore still need a kind of stable thioctic acid injection in the prior art.
Summary of the invention
The applicant is through the discovery that studies for a long period of time, and the injection that the mixture of thioctic acid and methionine is formed can improve the stability of thioctic acid effectively, has obtained beyond thought effect.And further discover on this basis to wherein adding arginine to have more excellent effect.Based on above-mentioned discovery, the applicant has accomplished the present invention.
The invention provides a kind of injection thioctic acid compositions, comprise thioctic acid, solubilizing agent, antioxidant.Wherein, three's mass ratio is 1: 0.1-5: 0.01-1; Preferred 1: 0.1-2: 0.03-0.6; More preferably 1: 0.5-1.5: 0.06-0.4.
Among the present invention, thioctic acid, chemistry by name 1; 2-Dithiolane-3-Pentanoic acid, being applied to thioctic acid of the present invention can be the R-thioctic acid, also can be its optical isomer S-thioctic acid; Or common racemization thioctic acid, the present invention does not limit the type of used thioctic acid.
Among the present invention, the effect of antioxidant is the oxidation Decomposition that prevents thioctic acid, can prevent better that thioctic acid is oxidized although increase the consumption of antioxidant, and too much antioxidant will increase the security risk of the present composition.In the present composition, described antioxidant comprises methionine; The applicant finds under study for action, and methionine during as antioxidant, is had better stablizing effect to wherein adding arginine, and the two mixes to use and has the obvious synergistic effect.Therefore antioxidant can also comprise methionine and arginic mixture among the present invention.Preferably, the present invention uses methionine and arginic mixture as antioxidant.When the present composition used methionine and arginic mixture as antioxidant, the mass ratio of the two can be 1: 0.01-1.
It is to be noted; As well known to those skilled in the art; Most aminoacid comprise methionine, arginine, all have its optical isomer; Yet optical isomer is for concrete solubilising, physical effect did not influence such as stable, so the methionine described in the present invention can be the mixture of L-methionine, D-methionine or two kinds of methionines; Described arginine can be D-arginine, L-arginine or two kinds of arginic mixture.
In the present composition, solubilizing agent improves the water solublity of thioctic acid, and regulates the pH environment of compositions, thereby makes thioctic acid more stable.Among the present invention, the pH scope that is fit to is 7-10, and used solubilizing agent can be sodium hydroxide or trometamol, preferably uses trometamol.
Further, the present invention also provides said preparation of compositions method, comprises the steps:
1. thioctic acid, solubilizing agent, antioxidant are joined proper amount of water for injection and perhaps contain in the aqueous solution of excipient substance, mix homogeneously can be that present composition solution reaches suitable pH value through the consumption of regulating solubilizing agent.
2. the solution with step 1 filters through suitable filter membrane, the sterilization of encapsulation back.
In step 1,, under the condition of nitrogen protection and lucifuge, carry out usually in order to prevent that thioctic acid is oxidized in the preparation process.
In preparation process 1 of the present invention, can use water dissolution solubilizing agent and antioxidant, but preferred use comprises the aqueous solution of hydrophilic solvent, for example contain the aqueous solution of polyhydric alcohol, preferred use Polyethylene Glycol aqueous solution.
In step 1 of the present invention, the described aqueous solution that contains excipient substance is meant the needs from preparation, the solution that those skilled in the art can be dissolved in the water suitable pharmaceutic adjuvant to obtain.To those skilled in the art; Thereby learn easily through using different auxiliary materials preparation different drug preparation; Understanding on the basis of essence of the present invention; Can know the adjuvant that is applicable to the present composition through different experiments, this is conspicuous improvement, still belongs to scope of the present invention.
In preparation process 2 of the present invention, composition solution is filtered the filtration method that can use this area commonly used, for example use the filter membrane of 0.45um or 0.22um specification to filter.Sterilizing methods can adopt common solution sterilization method, for example at 100-130 ℃ of heating 5-50min.
At last; The invention provides the purposes of above-mentioned composition in preparation medicine, cosmetics, food; Use association area method for preparing commonly used can the present composition be prepared into medicine, cosmetics, food, to those skilled in the art, this is conspicuous.
The medicine of the invention described above preparation of compositions can be the common injectable dosage forms in this area, for example can be after sterilization, to be packaged into injection; Can be in composition solution, add an amount of proppant such as mannitol, lactose etc. then lyophilization be prepared into freeze-dried powder. to those skilled in the art, these injection types all are conspicuous.
The specific embodiment
Following implementation method only is used to explain embodiment of the present invention, does not limit the present composition and only realizes with following proposal.Those skilled in the art can improve and change according to prior art on the basis of essence of the present invention following embodiment, still belong to protection scope of the present invention.
In following embodiment, used thioctic acid is the alpha-lipoic acid of racemization, and the applicant here points out, it is replaced with R or the S thioctic acid is suitable equally.
Embodiment 1
Thioctic acid 3g
Trometamol 3g
Methionine 0.07g
Under the condition of nitrogen and lucifuge; The trometamol of getting above-mentioned amount adds in the suitable quantity of water and adds thioctic acid, methionine successively after the dissolving; Add the injection water after the mixing and stirring to 100ml, and through being packaged into 20 bottles behind the 0.22um filtering with microporous membrane, at 121 ℃ of sterilization 20min.
Embodiment 2
Thioctic acid 5g
Trometamol 7g
Sodium hydroxide 0.2g
Methionine 0.15g
Arginine 0.15g
Under the condition of nitrogen and lucifuge; The trometamol of getting above-mentioned amount adds in the suitable quantity of water and adds thioctic acid, methionine, arginine, sodium hydroxide successively after the dissolving; Add the injection water after the mixing and stirring to 200ml; And through being packaged into 20 bottles behind the 0.22um filtering with microporous membrane, at 121 ℃ of sterilization 20min.
Embodiment 3
Thioctic acid 3g
Trometamol 3g
Methionine 0.1g
Arginine 0.05g
Under the condition of nitrogen and lucifuge; The trometamol of getting above-mentioned amount adds in the suitable quantity of water and adds thioctic acid, methionine, arginine successively after the dissolving; Add the injection water after the mixing and stirring to 100ml, and through being packaged into 20 bottles behind the 0.22um filtering with microporous membrane, at 121 ℃ of sterilization 20min.
Embodiment 4
Thioctic acid 5g
Trometamol 4g
Methionine 0.15g
Arginine 0.1g
Mannitol 1g
Under the condition of nitrogen and lucifuge; The trometamol of getting above-mentioned amount adds in the suitable quantity of water and adds thioctic acid, methionine, arginine, mannitol successively after the dissolving; Add the injection water after the mixing and stirring to 200ml; And through dressing up 40 bottles behind the 0.22um filtering with microporous membrane, through freezer dryer lyophilizing, the intrinsic pressure plug of case, outlet lock aluminium lid promptly gets freeze-dried powder.
Embodiment 5
R-thioctic acid 3g
Trometamol 5g
Methionine 0.1g
Under the condition of nitrogen and lucifuge; The trometamol of getting above-mentioned amount adds in the suitable quantity of water and adds R-thioctic acid, methionine successively after the dissolving; Add the injection water after the mixing and stirring to 100ml, and through being packaged into 20 bottles behind the 0.22um filtering with microporous membrane, at 121 ℃ of sterilization 20min.
Embodiment 6
S-thioctic acid 3g
Trometamol 2g
Sodium hydroxide 0.02g
Methionine 0.1g
Arginine 0.1g
Under the condition of nitrogen and lucifuge; Trometamol, the sodium hydroxide of getting above-mentioned amount add in the suitable quantity of water and add S-thioctic acid, methionine, arginine successively after the dissolving; Add the injection water after the mixing and stirring to 100ml; And through being packaged into 20 bottles behind the 0.22um filtering with microporous membrane, at 121 ℃ of sterilization 20min.
The comparative example 1
Thioctic acid 3g
Trometamol 3g
Arginine 0.1g
Under the condition of nitrogen and lucifuge; The trometamol of getting above-mentioned amount adds in the suitable quantity of water and adds thioctic acid, arginine successively after the dissolving; Add the injection water after the mixing and stirring to 100ml, and through being packaged into 20 bottles behind the 0.22um filtering with microporous membrane, at 121 ℃ of sterilization 20min.
The comparative example 2
Thioctic acid 3g
Trometamol 3g
Sodium sulfite 0.1g
Under the condition of nitrogen and lucifuge; The trometamol of getting above-mentioned amount adds in the suitable quantity of water and adds thioctic acid, sodium sulfite successively after the dissolving; Add the injection water after the mixing and stirring to 100ml, and through being packaged into 20 bottles behind the 0.22um filtering with microporous membrane, at 121 ℃ of sterilization 20min.
Stability test
Get embodiment 1,3 and comparative example's 1,2 injection respectively,, adopt the HPLC method to measure its thioctic acid content and its related substances, gained result such as following table then 60 ℃ of held 10 days:
Table 1: different antioxidant effect relatively
Visible by table 1, adopt methionine, methionine and arginine mixed compound can make the thioctic acid injection more stable, be superior to arginine, sodium sulfite effect as antioxidant.Wherein adopt methionine and arginine mixed compound significantly to be superior to all the other antioxidants, explain that methionine and arginine combination use has significant synergy as antioxidant effect.
Claims (13)
1. injection thioctic acid compositions; Contain thioctic acid, solubilizing agent, antioxidant; Said antioxidant comprises methionine, and said solubilizing agent is used to the PH environment that improves the water solublity of thioctic acid and regulate compositions, and pH value is 7-10; Wherein, the mass ratio of thioctic acid, solubilizing agent, antioxidant is 1: 0.1-5: 0.01-1.
2. according to the thioctic acid compositions of claim 1, said thioctic acid is the R-thioctic acid.
3. according to the thioctic acid compositions of claim 1, said thioctic acid is the S-thioctic acid.
4. according to the thioctic acid compositions of claim 1, said methionine is the L-methionine.
5. according to the thioctic acid compositions of claim 1, said methionine is the D-methionine.
6. according to the thioctic acid compositions of claim 1, also contain arginine in the antioxidant.
7. according to the thioctic acid compositions of claim 6, said arginine is the D-arginine.
8. according to the thioctic acid compositions of claim 6, said arginine is the L-arginine.
9. according to the thioctic acid compositions of claim 1, said solubilizing agent is selected from sodium hydroxide or trometamol.
10. according to the thioctic acid compositions of claim 1, described solubilizing agent is a trometamol.
11. according to the compositions of claim 1, wherein the mass ratio of thioctic acid, solubilizing agent, antioxidant is 1: 0.1-2: 0.03-0.6.
12. according to the compositions of claim 1, wherein the mass ratio of thioctic acid, solubilizing agent, antioxidant is 1: 0.5-1.5: 0.06-0.4.
13. the described preparation of compositions method of above-mentioned arbitrary claim comprises the steps:
Thioctic acid, solubilizing agent, antioxidant mixed dissolution in water, after stirring, are filtered.
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| CN201010293789A CN101961312B (en) | 2010-09-28 | 2010-09-28 | Lipoid acid composition for injection |
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| CN201010293789A CN101961312B (en) | 2010-09-28 | 2010-09-28 | Lipoid acid composition for injection |
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| CN102172352B (en) * | 2011-03-28 | 2013-05-08 | 江苏奥赛康药业股份有限公司 | Lipoic acid composition for injection and preparation method thereof |
| CN103655469B (en) * | 2013-12-19 | 2015-03-04 | 门毅 | Lipoic acid injection and preparation method thereof |
| CN105125480B (en) * | 2015-08-14 | 2018-04-13 | 南京海融制药有限公司 | A kind of liquid preparation of lipoic acid and preparation method thereof |
| CN105891202B (en) * | 2016-06-03 | 2017-08-22 | 广州市进德生物科技有限公司 | A kind of one-component TMB nitrite ions and preparation method thereof |
| CN112386570A (en) * | 2019-08-16 | 2021-02-23 | 江苏奥赛康药业有限公司 | Dextro-lipoic acid solution composition |
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| US20060099239A1 (en) * | 2002-04-15 | 2006-05-11 | Coleman Henry D | Dietary supplement for promoting removal of heavy metals from the body |
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| CN1750819A (en) * | 2003-01-09 | 2006-03-22 | 佩纳姆投资股份有限公司 | A method of treatment or prophylaxis of symptoms of herpes viral infection |
| CN1513547A (en) * | 2003-03-19 | 2004-07-21 | 杭州九源基因工程有限公司 | Stabilizing medicinal agent containing ciliary nerve nutritive factor analogue |
| CN1663567A (en) * | 2004-03-05 | 2005-09-07 | 罗靖 | Compound methionine vitamin B1Freeze-dried powder injection preparation and preparation method thereof |
| CN1895671A (en) * | 2005-12-08 | 2007-01-17 | 淮北市辉克药业有限公司 | Compound preparation for treating viral liver disease |
| CN1887882A (en) * | 2006-08-08 | 2007-01-03 | 武汉远大制药集团有限公司 | Dextro lipoic amidate and its prepn |
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| 乔运成.硫辛酸注射液治疗糖尿病周围神经病变的疗效观察.《临床合理用药》.2009,第2卷(第17期),62. * |
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| CN101961312A (en) | 2011-02-02 |
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