CN107789317A - A kind of lipoic acid parenteral solution and preparation method - Google Patents
A kind of lipoic acid parenteral solution and preparation method Download PDFInfo
- Publication number
- CN107789317A CN107789317A CN201610747617.9A CN201610747617A CN107789317A CN 107789317 A CN107789317 A CN 107789317A CN 201610747617 A CN201610747617 A CN 201610747617A CN 107789317 A CN107789317 A CN 107789317A
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- CN
- China
- Prior art keywords
- lipoic acid
- parenteral solution
- cosolvent
- water
- injection
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Classifications
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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
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
-
- 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
-
- 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
- A61K9/08—Solutions
Abstract
A kind of lipoic acid parenteral solution and preparation method.The invention belongs to pharmaceutical technology field, there is provided a kind of lipoic acid parenteral solution, be made up of lipoic acid, cosolvent, hydroxypropyl beta cyclodextrin and water for injection.Relevant material change unobvious, steady quality in lipoic acid parenteral solution long term test prepared by the present invention, and be easy to produce greatly.
Description
Technical field：
The invention belongs to drug stent field, and in particular to a kind of lipoic acid parenteral solution and preparation method thereof.
Background technology：
Lipoic acid, chemical name：(±) -5- [3- (1,2- dithiolanes)]-valeric acid
Lipoic acid is the natural products separated first from pork liver by ReedShi, and it is pyruvic acid and tricarboxylic acid cycle
The cofactors of the oxidative deamination reaction of middle α-ketoglutaric acid.Lipoic acid for the relevant a variety of diseases of active oxidation free radical such as
Diabetes, ischemia reperfusion injury, heavy metal poisoning, radiolesion, degenerative neuropathy and HIV infection
Deng with prevention and treatment effect.
Lipoic acid is largely used to treat on the DPN of diabetes at present.Isolated test shows that this product can reduce god
Lipid oxidation phenomenon through tissue, this product may prevent the glycosylation of protein；And aldose reductase can be suppressed, thus can
Glucose or galactolipin is prevented to transform into sorbierite, so lipoic acid can prevent diabetes, control blood glucose and prevent because of height
DPN caused by blood glucose.
Lipoic acid is to remove free radical, have strong antioxidant action, and its parenteral solution is placed relevant material and substantially surpassed for a long time
Mark, decoction color burn, pH value decline, less stable.
For these problems, there are some technical schemes to be improved both at home and abroad.There is researcher to be made powder pin
Agent, but because lipoic acid water solubility is poor, occurs redissolving more difficult or the problem of be not easy to redissolve, and its sterility assurance level is less than
Terminal sterilization is horizontal.Also there is researcher to be made parenteral solution, add the excipient such as meglumine, ethylenediamine as its cosolvent,
But obtained parenteral solution long-time stability are bad, relevant material constantly increases；Also researcher adds antioxidant in parenteral solution
Sodium hydrogensulfite, but pH value constantly increases in the long-term placement process of parenteral solution of prescription preparation, and stability can not be protected
Card.
The content of the invention：
In view of the shortcomings of the prior art, it is an object of the invention to provide a kind of lipoic acid parenteral solution and preparation method thereof.Hair
A person of good sense is found surprisingly that after adding hydroxypropyl-β-cyclodextrin, the stability of parenteral solution is carried by substantial amounts of experiment sieving
Height, it is in particular in and is tested by long-time stability, relevant material, pH value is substantially without significant change in sample.
Contain hydroxypropyl-β-cyclodextrin in the parenteral solution of the present invention, substantially expanded after hydroxypropyl-β-cyclodextrin water suction, will
Lipoic acid ethylenediamine salt is included in the hole of cyclodextrin molecular, the oxygen completely cut off in air and water, serves certain guarantor
Shield acts on.
Technical scheme is as follows：
A kind of lipoic acid parenteral solution, is made up of lipoic acid, cosolvent, hydroxypropyl-β-cyclodextrin, water for injection.
Described lipoic acid parenteral solution, the one kind of cosolvent in ethylenediamine, tromethamine.
Described lipoic acid parenteral solution, it is characterised in that cosolvent is ethylenediamine.
The mass ratio of described lipoic acid parenteral solution, lipoic acid and cosolvent is 1：0.2-0.25, preferably 1：0.23.
The mass ratio of described lipoic acid parenteral solution, lipoic acid and hydroxypropyl-β-cyclodextrin is 1：1-10, preferably 1：2-5,
Further preferably 1：2.5.
A kind of preparation method of the lipoic acid parenteral solution, comprises the following steps：
(1) first cosolvent is placed in the water for injection for being cooled to room temperature, be well mixed；
(2) lipoic acid is placed in cosolvent solution, stirring is to being completely dissolved；
(3) hydroxypropyl-β-cyclodextrin is added, stirring is to being completely dissolved；
(4) mend and add to the full amount of water for injection；
(5) medicine liquid irrigation is encapsulated in brown ampoule；
(6) sterilize.
Embodiment：
Following examples further describe the preparation process and beneficial effect of the present invention, and embodiment is only used for the mesh of illustration
, do not limit the scope of the invention, while those of ordinary skill in the art according to the obvious change made of the present invention and
Modification is also contained within the scope of the invention.
Embodiment 1
Prescription：
Preparation method：
(1) first recipe quantity ethylenediamine is placed in the water for injection for being cooled to room temperature, water for injection is the 80% of full dose, is stirred
To being completely dissolved；
(2) lipoic acid of recipe quantity is added in above-mentioned solution, stirring is to being completely dissolved；
(3) hydroxypropyl-β-cyclodextrin of recipe quantity is added, stirring is to being completely dissolved；
(4) mend and add to the full amount of water for injection；
(5) medicine liquid irrigation is encapsulated in brown ampoule；
(6) sterilize.
Embodiment 2
Prescription：
Preparation method：
(1) first recipe quantity tromethamine is placed in the water for injection for being cooled to room temperature, water for injection is the 80% of full dose, is stirred
Mix to being completely dissolved；
(2) lipoic acid of recipe quantity is added in above-mentioned solution, stirring is to being completely dissolved；
(3) hydroxypropyl-β-cyclodextrin of recipe quantity is added, stirring is to being completely dissolved；
(4) mend and add to the full amount of water for injection；
(5) medicine liquid irrigation is encapsulated in brown ampoule；
(6) sterilize.
Embodiment 3
Prescription：
Preparation method is the same as embodiment 1.
Embodiment 4
Prescription：
Preparation method is the same as embodiment 1.
Embodiment 5
Prescription：
Preparation method is the same as embodiment 1.
Comparative example 1
Prescription：
Preparation method：
(1) first recipe quantity ethylenediamine is placed in the water for injection for being cooled to room temperature, water for injection is the 80% of full dose, is stirred
To being completely dissolved；
(2) lipoic acid of recipe quantity and sodium hydrogensulfite are added in above-mentioned solution, stirring is to being completely dissolved；
(3) mend and add to the full amount of water for injection；
(4) medicine liquid irrigation is encapsulated in brown ampoule；
(5) sterilize.
Comparative example 2
Prescription：
Preparation method：
(1) first recipe quantity ethylenediamine is placed in the water for injection for being cooled to room temperature, water for injection is the 80% of full dose, is stirred
To being completely dissolved；
(2) lipoic acid of recipe quantity and meglumine are added in above-mentioned solution, stirring is to being completely dissolved；
(3) mend and add to the full amount of water for injection；
(4) medicine liquid irrigation is encapsulated in brown ampoule；
(5) sterilize.
Comparative example 3
Prescription：
Preparation method is the same as embodiment 1.
Comparative example 4
Prescription：
Preparation method is the same as embodiment 1.
Comparative example 5
Prescription：
Lipoic acid 30g
Hydroxypropyl-β-cyclodextrin 75g
Water for injection adds to 1.2L
Preparation method：
(1) first recipe quantity lipoic acid is placed in the water for injection for being cooled to room temperature, water for injection is the 80% of full dose, is stirred
To being completely dissolved；
(2) hydroxypropyl-β-cyclodextrin of recipe quantity is added, stirring is to being completely dissolved；
(3) mend and add to the full amount of water for injection；
(4) medicine liquid irrigation is encapsulated in brown ampoule；
(5) sterilize.
Sample is placed for a long time 24 months, experimental condition (25 DEG C, relative humidity 60% ± 10%) is in the 0th, 6,12,18,24
Moon sampling detection, long-term test results see the table below
As can be seen from the above table, keep stable by long term test embodiment 1-5 parenteral solution pH value, relevant material change
Unobvious, it is seen that foreign matter meets regulation；Comparative example 1 constantly increases with the extension of standing time, pH value, the change of relevant material compared with
Substantially, at 18 months, it is seen that foreign bodies detection is unqualified；Comparative example 2 is with the extension of time, pH value constantly declines, December
When, it is seen that foreign bodies detection is unqualified, and color burn, less stable.The relevant material at 18th month of comparative example 5 becomes
Change larger, it is seen that foreign bodies detection is unqualified, comparative example 3 with 4 at 24th month relevant material change greatly, it is seen that foreign matter
Detect unqualified.Compare, relevant material change unobvious, quality are steady in lipoic acid parenteral solution long term test prepared by the present invention
It is fixed.
Claims (9)
1. a kind of lipoic acid parenteral solution, it is characterised in that by lipoic acid, cosolvent, hydroxypropyl-β-cyclodextrin, water for injection group
Into.
2. lipoic acid parenteral solution according to claim 1, it is characterised in that cosolvent is in ethylenediamine, tromethamine
One kind.
3. lipoic acid parenteral solution according to claim 1, it is characterised in that cosolvent is ethylenediamine.
4. lipoic acid parenteral solution according to claim 1, it is characterised in that the mass ratio of lipoic acid and cosolvent is 1：
0.2-0.25。
5. lipoic acid parenteral solution according to claim 1, it is characterised in that the mass ratio of lipoic acid and cosolvent is 1：
0.23。
6. lipoic acid parenteral solution according to claim 1, it is characterised in that the matter of lipoic acid and hydroxypropyl-β-cyclodextrin
Amount is than being 1：1-10.
7. lipoic acid parenteral solution according to claim 1, it is characterised in that the matter of lipoic acid and hydroxypropyl-β-cyclodextrin
Amount is than being 1：2-5.
8. lipoic acid parenteral solution according to claim 1, it is characterised in that the matter of lipoic acid and hydroxypropyl-β-cyclodextrin
Amount is than being 1：2.5.
9. the preparation method of lipoic acid parenteral solution described in a kind of claim 1, it is characterised in that comprise the following steps：
(1) first cosolvent is placed in the water for injection for being cooled to room temperature, be well mixed；
(2) lipoic acid is placed in cosolvent solution, stirring is to being completely dissolved；
(3) hydroxypropyl-β-cyclodextrin is added, stirring is to being completely dissolved；
(4) mend and add to the full amount of water for injection；
(5) medicine liquid irrigation is encapsulated in brown ampoule；
(6) sterilize.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610747617.9A CN107789317B (en) | 2016-08-29 | 2016-08-29 | Lipoic acid injection and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610747617.9A CN107789317B (en) | 2016-08-29 | 2016-08-29 | Lipoic acid injection and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN107789317A true CN107789317A (en) | 2018-03-13 |
| CN107789317B CN107789317B (en) | 2021-07-02 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610747617.9A Active CN107789317B (en) | 2016-08-29 | 2016-08-29 | Lipoic acid injection and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110237028A (en) * | 2019-06-20 | 2019-09-17 | 南京知和医药科技有限公司 | A kind of lipoic acid injection and preparation process |
| CN113197845A (en) * | 2020-12-16 | 2021-08-03 | 南京海融制药有限公司 | Lipoic acid tromethamine injection and preparation method thereof |
| IT202000009577A1 (en) | 2020-04-30 | 2021-10-30 | Fatro Spa | INJECTABLE LIPOIC ACID FORMULATIONS FOR THE TREATMENT OF OXIDATIVE STRESS AND METABOLIC DISORDERS |
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| EP1707217A1 (en) * | 2004-12-17 | 2006-10-04 | Wacker Chemie AG | Process for preparing an alpha lipoic acid/cyclodextrin complex and product prepared |
| CN1947716A (en) * | 2005-10-14 | 2007-04-18 | 车瓯 | Clathrate compound of alpha-lipoic acid-cyclodextrin derivatives, and its prepn. method |
| WO2012014746A1 (en) * | 2010-07-30 | 2012-02-02 | 株式会社シクロケム | Α-lipoic acid complex |
| US20130108605A1 (en) * | 2010-03-25 | 2013-05-02 | The University Of Kentucky Research Foundation | Method of ameliorating oxidative stress and supplementing the diet |
| CN103655469A (en) * | 2013-12-19 | 2014-03-26 | 门毅 | Prescription and preparation technology of lipoic acid injection combination |
| CN105616343A (en) * | 2014-11-04 | 2016-06-01 | 蓬莱诺康药业有限公司 | Lipoic acid injection liquid and preparation method thereof |
-
2016
- 2016-08-29 CN CN201610747617.9A patent/CN107789317B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1707217A1 (en) * | 2004-12-17 | 2006-10-04 | Wacker Chemie AG | Process for preparing an alpha lipoic acid/cyclodextrin complex and product prepared |
| CN1947716A (en) * | 2005-10-14 | 2007-04-18 | 车瓯 | Clathrate compound of alpha-lipoic acid-cyclodextrin derivatives, and its prepn. method |
| US20130108605A1 (en) * | 2010-03-25 | 2013-05-02 | The University Of Kentucky Research Foundation | Method of ameliorating oxidative stress and supplementing the diet |
| WO2012014746A1 (en) * | 2010-07-30 | 2012-02-02 | 株式会社シクロケム | Α-lipoic acid complex |
| CN103655469A (en) * | 2013-12-19 | 2014-03-26 | 门毅 | Prescription and preparation technology of lipoic acid injection combination |
| CN105616343A (en) * | 2014-11-04 | 2016-06-01 | 蓬莱诺康药业有限公司 | Lipoic acid injection liquid and preparation method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110237028A (en) * | 2019-06-20 | 2019-09-17 | 南京知和医药科技有限公司 | A kind of lipoic acid injection and preparation process |
| IT202000009577A1 (en) | 2020-04-30 | 2021-10-30 | Fatro Spa | INJECTABLE LIPOIC ACID FORMULATIONS FOR THE TREATMENT OF OXIDATIVE STRESS AND METABOLIC DISORDERS |
| EP3903768A1 (en) | 2020-04-30 | 2021-11-03 | FATRO S.p.A. | Injectable formulations of lipoic acid for the treatment of oxidative stress and metabolic alterations |
| CN113197845A (en) * | 2020-12-16 | 2021-08-03 | 南京海融制药有限公司 | Lipoic acid tromethamine injection and preparation method thereof |
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| Publication number | Publication date |
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| CN107789317B (en) | 2021-07-02 |
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