CN101961312A - Lipoid acid composition for injection - Google Patents
Lipoid acid composition for injection Download PDFInfo
- Publication number
- CN101961312A CN101961312A CN 201010293789 CN201010293789A CN101961312A CN 101961312 A CN101961312 A CN 101961312A CN 201010293789 CN201010293789 CN 201010293789 CN 201010293789 A CN201010293789 A CN 201010293789A CN 101961312 A CN101961312 A CN 101961312A
- Authority
- CN
- China
- Prior art keywords
- thioctic acid
- methionine
- antioxidant
- compositions
- arginine
- 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.)
- Granted
Links
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 separating from Hepar Sus domestica, 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 nerve conduction velocity 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.
At 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 as German patent application EP0318891 in 1992, thioctic acid is mixed with trometamol and arginine, there is bigger defective in this injection, the arginine consumption (needs 30% arginine greatly in the unit medicine on the one hand, calculate with mole), the injection thioctic acid content of unit mole is lower, need increase the injection consumption when causing clinical use; Should write out a prescription on the other hand and increase the effect of thioctic acid stability and unsatisfactory.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 and can have more excellent effect to wherein adding arginine.Based on above-mentioned discovery, the applicant has finished 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 there is 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 described preparation of compositions method, comprises the steps:
1. thioctic acid, solubilizing agent, antioxidant are joined proper amount of water for injection or contain in the aqueous solution of excipient substance, mix homogeneously can be that present composition solution reaches suitable pH value by the consumption of regulating solubilizing agent.
2. the solution with step 1 filters by 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 for 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 by using different adjuvants to prepare different pharmaceutical preparation, understanding on the basis of essence of the present invention, can know the adjuvant that is applicable to the present composition by 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 preparation method commonly used the present composition can 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 to be packaged into injection after sterilization; Can be in composition solution, add an amount of proppant such as mannitol, lactose etc. then lyophilization be prepared into freeze-dried powder. for those skilled in the art, these injection types all are conspicuous.
The specific embodiment
Following implementation method only is used to illustrate embodiments 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 the following embodiments, 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, placed 10 days down, adopt the HPLC method to measure its thioctic acid content and its related substances then, gained result such as following table at 60 ℃:
Table 1: different antioxidant effect relatively
By table 1 as seen, adopt methionine, methionine and arginine mixed compound can make the thioctic acid injection more stable, be better than arginine, sodium sulfite effect as antioxidant.Wherein adopt methionine and arginine mixed compound significantly to be better than all the other antioxidants, illustrate that methionine and arginine are used in combination and have significant synergy as antioxidant effect.
Claims (15)
1. an injection thioctic acid compositions contains thioctic acid, solubilizing agent, antioxidant, and described antioxidant comprises methionine.
2. according to the thioctic acid compositions of claim 1, described thioctic acid is the R-thioctic acid.
3. according to the thioctic acid compositions of claim 1, described thioctic acid is the S-thioctic acid.
4. according to the thioctic acid compositions of claim 1, described methionine is the L-methionine.
5. according to the thioctic acid compositions of claim 1, described 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, described arginine is the D-arginine.
8. according to the thioctic acid compositions of claim 6, described arginine is the L-arginine.
9. according to the thioctic acid compositions of claim 1, described solubilizing agent is selected from sodium hydroxide or trometamol.
10. according to the thioctic acid compositions of claim 9, described solubilizing agent is a trometamol.
11. according to the thioctic acid compositions of claim 9, its pH value is 7-10.
12. the described compositions of above arbitrary claim, wherein the mass ratio of thioctic acid, solubilizing agent, antioxidant is 1: 0.1-5: 0.01-1.
13. according to the compositions of claim 12, wherein the mass ratio of thioctic acid, solubilizing agent, antioxidant is 1: 0.1-2: 0.030.6.
14. according to the compositions of claim 12, wherein the mass ratio of thioctic acid, solubilizing agent, antioxidant is 1: 0.5-1.5: 0.06-0.4.
15. 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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010293789A CN101961312B (en) | 2010-09-28 | 2010-09-28 | Lipoid acid composition for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010293789A CN101961312B (en) | 2010-09-28 | 2010-09-28 | Lipoid acid composition for injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101961312A true CN101961312A (en) | 2011-02-02 |
| CN101961312B CN101961312B (en) | 2012-10-03 |
Family
ID=43514491
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010293789A Active CN101961312B (en) | 2010-09-28 | 2010-09-28 | Lipoid acid composition for injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101961312B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102172352A (en) * | 2011-03-28 | 2011-09-07 | 江苏奥赛康药业有限公司 | Lipoic acid composition for injection and preparation method thereof |
| CN103655469A (en) * | 2013-12-19 | 2014-03-26 | 门毅 | Prescription and preparation technology of lipoic acid injection combination |
| CN105125480A (en) * | 2015-08-14 | 2015-12-09 | 南京海融医药科技有限公司 | Lipoic acid liquid preparation and preparation method thereof |
| CN105891202A (en) * | 2016-06-03 | 2016-08-24 | 广州市进德生物科技有限公司 | Single-component TMB color developing solution 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 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 menonine and Vitamin B1 freeze-dried injection and its preparation |
| 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 |
| US20060099239A1 (en) * | 2002-04-15 | 2006-05-11 | Coleman Henry D | Dietary supplement for promoting removal of heavy metals from the body |
| 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 |
| 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 |
-
2010
- 2010-09-28 CN CN201010293789A patent/CN101961312B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060099239A1 (en) * | 2002-04-15 | 2006-05-11 | Coleman Henry D | Dietary supplement for promoting removal of heavy metals from the body |
| 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 menonine and Vitamin B1 freeze-dried injection and its preparation |
| 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 |
Non-Patent Citations (1)
| Title |
|---|
| 《临床合理用药》 20090930 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 62 1-15 第2卷, 第17期 2 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102172352A (en) * | 2011-03-28 | 2011-09-07 | 江苏奥赛康药业有限公司 | Lipoic acid composition for injection and preparation method thereof |
| CN103655469A (en) * | 2013-12-19 | 2014-03-26 | 门毅 | Prescription and preparation technology of lipoic acid injection combination |
| CN105125480A (en) * | 2015-08-14 | 2015-12-09 | 南京海融医药科技有限公司 | Lipoic acid liquid preparation 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 |
| CN105891202A (en) * | 2016-06-03 | 2016-08-24 | 广州市进德生物科技有限公司 | Single-component TMB color developing solution 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101961312B (en) | 2012-10-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2904838C (en) | Method for treatment of parkinson's disease | |
| CN101961312B (en) | Lipoid acid composition for injection | |
| RU2684105C2 (en) | Dopa decarboxylase inhibitor compositions | |
| JP6892494B2 (en) | Aqueous formulation containing paracetamol and ibuprofen | |
| CN101984968A (en) | Preparation method of pharmaceutical preparation of antitumor agent temozolomide | |
| BR112020019192A2 (en) | PHARMACEUTICAL COMPOSITION THAT UNDERSTANDS DEOXICOLIC ACID | |
| JP5177785B2 (en) | Drugs for perioperative patients | |
| CN1893938A (en) | Pregabalin composition | |
| CN105078909A (en) | Cisatracurium besilate freeze dried composition for injection and preparation method thereof | |
| JP2019502720A (en) | Vancomycin formulation | |
| US20190231721A1 (en) | Sulfonamide pharmaceutical composition | |
| CN101978945B (en) | A kind of ibuprofen medicinal composition | |
| CN1493283A (en) | Edalavon powder for ampoul injection having good stability and its preparation method | |
| SE538425C2 (en) | Pharmaceutical compositions comprising levodopa, carbidopa and a comt inhibitor and method of administration thereof | |
| CN104800172A (en) | Carbazochrome sodium sulfonate powder injection for injection and preparation method thereof | |
| CN102008461B (en) | A kind of ibuprofen drug composite for injection | |
| CN103012192B (en) | Novel aceglutamide compound and pharmaceutical composition thereof | |
| CN103610693A (en) | Parenteral nutrition injection composition | |
| CN106511373B (en) | A kind of compound orthocoll oral administration solution and preparation method thereof | |
| CN102757471B (en) | Novel active cytidine disodium triphosphate compound and pharmaceutical composition thereof | |
| CN101703466A (en) | Borneol injection and preparation method thereof | |
| EP3466430B1 (en) | Pharmaceutical composition | |
| CN110151688A (en) | A kind of ambroxol hydrochloride injection composition and preparation method thereof | |
| JP2007045788A (en) | Method for preparing aqueous solution of glycyrrhizinic acid having high concentration | |
| WO2017130576A1 (en) | Medicinal composition |
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 | ||
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: 210047 room 1203, building D, 606 ningliu Road, Changlu street, Jiangbei new district, Nanjing City, Jiangsu Province Patentee after: Nanjing century Bokang Pharmaceutical Technology Co.,Ltd. Address before: 100070 Beijing science and Technology Park of Fengtai Haiying Road No. 9 Jintang building 3 203 Patentee before: BEIJING CENTURY BIOCOM PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210222 Address after: 226600 No. 8, Xiao Xing Avenue, Chengdong Town, Haian City, Nantong, Jiangsu. Patentee after: Nantong Ji Zhi Intellectual Property Service Co.,Ltd. Address before: 210047 room 1203, building D, 606 ningliu Road, Changlu street, Jiangbei new district, Nanjing City, Jiangsu Province Patentee before: Nanjing century Bokang Pharmaceutical Technology Co.,Ltd. |