CN108567775B - Application of lipoic acid in preparation of pharmaceutical composition for treating pressure-loaded myocardial damage - Google Patents
Application of lipoic acid in preparation of pharmaceutical composition for treating pressure-loaded myocardial damage Download PDFInfo
- Publication number
- CN108567775B CN108567775B CN201810788077.8A CN201810788077A CN108567775B CN 108567775 B CN108567775 B CN 108567775B CN 201810788077 A CN201810788077 A CN 201810788077A CN 108567775 B CN108567775 B CN 108567775B
- Authority
- CN
- China
- Prior art keywords
- lipoic acid
- myocardial
- myocardial damage
- aldh2
- pressure
- 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
Images
Classifications
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Abstract
The invention relates to a clinical medicine lipoic acid for treating pressure-loaded myocardial damage, which is added on the basis of standard treatment on a patient with pressure-loaded myocardial damage, can improve the activity of myocardial mitochondrial acetaldehyde dehydrogenase 2(ALDH2), improve the energy metabolism of myocardial mitochondria, inhibit oxidative stress, play a role in protecting the heart and delay the occurrence and development of myocardial damage. Its advantages are: (1) the lipoic acid can improve the energy metabolism of the myocardial mitochondria by reducing the activity of ALDH2 in the myocardial mitochondria and inhibit oxidative stress, thereby playing a role in protecting the myocardial damage after pressure overload and improving the life quality of patients. (2) Develops the new application of the lipoic acid and leads the lipoic acid to be better applied. (3) Provides a new medicine research direction for the pressure load myocardial damage diseases and has good application prospect.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of lipoic acid in preparing a pharmaceutical composition for treating pressure-loaded myocardial injury.
Background
Cardiac stress overload due to various causes is one of the common causes of myocardial damage and remodeling. The common clinical pressure overload diseases mainly comprise hypertension, aortic stenosis and the like, but the hypertension is taken as the main primary lesion in the diseases at present by combining the current national conditions and the implementation of effective instruments for treating abnormal valves. Although the current antihypertensive and anti-myocardial remodeling drugs have made great progress, the myocardial damage and remodeling cannot be completely reversed, and finally severe myocardial damage is caused, so that a new target point for treating myocardial damage needs to be discovered from a new perspective.
Abnormal energy metabolism of the heart muscle is an important pathological basis of the damage of the heart muscle, and mitochondria play a key role as a main site for supplying ATP. The analysis of the function of mitochondrial energy metabolism reconstruction in the occurrence of different types of myocardial injuries and the intervention and regulation thereof is helpful for early finding myocardial injury risk factors and more effectively improving the myocardial injury prognosis. The previous research focuses on mitochondria of failing myocardium, and nearly hundreds of mitochondria differential expression proteins are screened out through proteomics, wherein the proteins comprise acetaldehyde dehydrogenase2 (aldehydoreogenase 2, ALDH 2). ALDH2 is a key enzyme involved in mitochondrial glycolipid metabolism, has a redox-sensitive sulfhydryl on its active site, and when oxygen radicals increase in vivo, it promotes the formation of disulfide bond in ALDH2 active site to inactivate it. Based on the massive distribution of the enzyme in myocardium, a series of researches of ALDH2 in the field of myocardial injury and protection are carried out, the fact that the enzyme can play a role in protecting the heart by maintaining mitochondrial metabolism homeostasis under the stimulation of cardiovascular pathologies such as pressure overload, ischemia, alcohol and the like is found, and the fact that ALDH2 is a precondition for improving the transplantation curative effect in the field of treating myocardial injury by stem cells is also proved, and the ALDH2 can be a new target point for treating various diseases due to the key position and significance of the ALDH in cytoprotection in various human diseases.
Lipoic Acid (LA) belongs to vitamin B compounds, and has a closed ring structure formed by sulfur and carbon atoms, and the electron density of the LA is relatively high, so that the LA has relatively strong oxidation resistance. LA has good prevention and treatment effects on diabetes, diabetic complications, various cerebral and neurodegenerative diseases, aging and the like. The role of LA in cardiovascular disease is of increasing interest, and studies have shown that LA can restore its activity by reducing disulfides at the active site of mitochondrial ALDH2, thereby improving nitrate tolerance. Later, researchers discovered that LA also protects diabetic cardiomyopathy and acute ischemia-reperfusion injury by reducing ALDH2 activity. The lipoic acid has strong antioxidant property and rare adverse reactions (incidence rate is less than or equal to 1/10,000), so that the lipoic acid widely promotes the clinical application of the lipoic acid, and the lipoic acid clinically has two forms of intravenous injection and oral capsules at present, and is suitable for abnormal sensations caused by diabetic peripheral neuropathy. However, the treatment advantages of lipoic acid on myocardial damage after pressure overload are not discovered at present, and the prognosis of pressure-loaded myocardial damage is still worried.
The Chinese patent application: CN102210764B discloses an application of sweet almond oil in preparing a medicine for treating myocardial ischemia-reperfusion injury, the effective component of the medicine for preventing and treating myocardial ischemia-reperfusion injury prepared from sweet almond oil is used in the form of a soft capsule, and the soft capsule is directly prepared from sweet almond oil by adopting a preparation method of a conventional soft capsule. The sweet almond oil is proved to be capable of improving the hypoxia tolerance of rat myocardial tissues, enhancing the tolerance of the myocardial tissues to ischemia reperfusion myocardial injuries, improving the oxidation resistance of the rat myocardial tissues subjected to ischemia reperfusion and reducing the injury degree of the rat myocardial tissues subjected to ischemia reperfusion. The almond oil of the invention is a natural edible substance which takes unsaturated fatty acid as a main effective component, and can not cause toxic or side effect to human body after long-term use within a certain dosage range.
The Chinese patent application: CN106620642A discloses a western medicine composition for treating hyperglycemia, which comprises the following main raw materials in parts by weight: 68-20 parts of vitamin B, 15-17 parts of gypenoside XLVI, 0.5-0.9 part of paclitaxel, 4-17 parts of 5-hydroxytryptamine, 18-25 parts of dehydroevodiamine, 11-15 parts of morin G, 4-9 parts of wilfordine, 7-12 parts of allicin and 5-16 parts of scutellarin methyl ester. The medicine of the invention strictly selects the raw material components according to the cognitive mechanism of hyperglycemia, thereby achieving the purpose of comprehensive rehabilitation, but the method uses more medicinal materials and is inconvenient to use. However, no report is found about the application of the lipoic acid in the preparation of the pharmaceutical composition for treating the pressure-loaded myocardial damage.
Disclosure of Invention
The first purpose of the present invention is to provide a new use of lipoic acid against the deficiencies of the prior art.
The second purpose of the invention is to provide the working mechanism of lipoic acid in the treatment of myocardial damage diseases, aiming at the defects of the prior art.
The third purpose of the present invention is to provide a pharmaceutical composition for treating myocardial damage, which is aimed at overcoming the shortcomings of the prior art.
In order to achieve the first purpose, the invention adopts the technical scheme that:
application of lipoic acid in preparing medicine for treating myocardial damage is disclosed.
As a preferred embodiment of the invention, the medicine is a clinically acceptable pharmaceutical preparation prepared by taking lipoic acid as a main component and adding pharmaceutically acceptable auxiliary materials or auxiliary components.
As a preferred embodiment of the present invention, the pharmaceutical preparation includes both oral preparations and injection preparations.
As a preferred embodiment of the present invention, the oral formulation is an oral capsule, and the injectable formulation is an intravenous injection.
As a preferred embodiment of the present invention, the myocardial injury is a pressure-loaded myocardial injury.
In order to achieve the second object, the invention adopts the technical scheme that:
the lipoic acid can improve the energy metabolism of the myocardial mitochondria by reducing the activity of ALDH2 in the myocardial mitochondria and inhibit oxidative stress, thereby playing a role in protecting the myocardial damage after pressure overload.
In order to achieve the third object, the invention adopts the technical scheme that:
a pharmaceutical composition for treating myocardial injury, which comprises the lipoic acid and a standard medicament for treating myocardial injury.
As a preferred embodiment of the present invention, the standard drugs include adenosine disodium triphosphate, vitamin C, mepiride, Reyinnin, Disha, epirubicin, pyridaben, damimekang, Ketoli, and Imolium.
As shown in fig. 1, lipoic acid can restore its activity by reducing disulfide at the active site of mitochondrial ALDH2, improve nitrate tolerance, and improve diabetic cardiomyopathy and acute ischemia-reperfusion injury, so it is presumed that lipoic acid can improve myocardial mitochondrial energy metabolism by reducing the activity of ALDH2 in myocardial mitochondria, and inhibit oxidative stress, thereby playing a role in protecting myocardial injury after pressure overload.
The lipoic acid capsule using method comprises the following steps: the specification of the lipoic acid capsule is 0.1g, and the usage and dosage are as follows: is orally administered at a dose of 0.2 g/time and 3 times/day, or 0.6 g/time and 1 time/day half an hour before breakfast.
The application method of the lipoic acid intravenous injection comprises the following steps: the specification of the lipoic acid injection is 12ml, 0.3g, the usage amount is as follows: it is used for intravenous injection. Intravenous injection should be slow with a maximum rate of 50mg lipoic acid per minute. Sodium chloride injection can also be added for intravenous drip, for example, 250-.
The invention has the advantages that:
1. compared with the traditional myocardial damage treatment such as cardiotonic, diuretic and anti-vascular treatment, lipoic acid with extremely rare adverse reactions is used for treating patients with myocardial damage after pressure overload, and the lipoic acid can improve the energy metabolism of myocardial mitochondria and inhibit oxidative stress by reducing the activity of ALDH2 in the myocardial mitochondria, thereby playing a role in protecting the myocardial damage after pressure overload and improving the life quality of the patients.
2. Develops the new application of the lipoic acid and leads the lipoic acid to be better applied.
3. Provides a new medicine research direction for the pressure load myocardial damage diseases and has good application prospect.
Drawings
FIG. 1 is a schematic representation of the disulfide bond of the active site of lipoic acid reducing ALDH 2. When the oxygen free radicals are increased in vivo, the formation of disulfide bond at the active site of ALDH2 is promoted to inactivate the oxygen free radicals. Lipoic acid can restore its activity by reducing the disulfide at the ALDH2 active site.
FIG. 2 is a graph showing the result of EF value analysis of four groups of mice in example 3.
FIG. 3 is a graph showing the result of FS value analysis of four groups of mice in example 3.
FIG. 4 is an echocardiogram of four groups of mice in example 3.
FIG. 5 is a graph showing the results of lung weight ratio analysis of four groups of mice in example 3.
FIG. 6 shows the DHE staining results and statistical plots of four groups of mice in example 3.
FIG. 7 is a graph showing the results of the activity assay of four groups of mouse cardiac ALDH2 in example 3 (ns: no statistical difference; P: P < 0.05; P: P < 0.01).
Detailed Description
The invention will be further illustrated with reference to specific embodiments. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Furthermore, it should be understood that various changes and modifications can be made by those skilled in the art after reading the disclosure of the present invention, and equivalents fall within the scope of the appended claims.
EXAMPLE 1 preparation of capsules
The preparation method of the lipoic acid capsule comprises the following steps:
lipoic acid is purchased from Jiangsu Wanchuan medical health industry group, Inc.
(1) Taking 100g of lipoic acid, micronizing, and sieving with a 200-mesh sieve to obtain lipoic acid fine powder;
(2) putting 50g of poloxamer 237 into a suitable container, putting the container into a water bath at 49-50 ℃, heating the mixture to a molten liquid state, adding 100g of lipoic acid fine powder, quickly and fully stirring the mixture at 49-50 ℃ until the mixture is uniformly mixed, standing the mixture to remove bubbles, spreading the mixture into a thin layer, putting the thin layer into a refrigerator at-5 ℃, quickly cooling the thin layer, taking out the mixture after the mixture is completely solidified, crushing the mixture, putting the mixture into a vacuum drier, drying the mixture for 24 hours at 35 ℃, crushing the mixture, and sieving the crushed mixture by a 100-mesh sieve to obtain the lipoic acid.
(3) And (3) adding 82g of microcrystalline cellulose, 10g of lactose, 8g of sodium carboxymethyl starch and 4g of magnesium stearate into the lipoic acid solid dispersion in the step (2), sieving the filler, the disintegrant and the lubricant with a 100-mesh sieve, preparing granules by using a 2% hydroxypropyl methylcellulose aqueous solution as a binding agent, and filling the granules into capsules to obtain 1000 lipoic acid capsules, wherein each capsule contains 0.1g of lipoic acid.
EXAMPLE 2 preparation of Intravenous Injection (II)
The preparation method of the lipoic acid intravenous injection comprises the following steps:
lipoic acid is purchased from Jiangsu Wanchuan medical health industry group, Inc.
(1) Putting cosolvent ethylenediamine into injection water cooled to room temperature, and mixing uniformly;
(2) according to the mass ratio of 1: 0.23 weight of lipoic acid and cosolvent ethylenediamine, placing the lipoic acid in the cosolvent ethylenediamine solution, and stirring until the lipoic acid and the cosolvent ethylenediamine are completely dissolved;
(3) weighing hydroxypropyl- β -cyclodextrin according to the mass ratio of the lipoic acid to the hydroxypropyl- β -cyclodextrin of 1: 2.5, adding the hydroxypropyl- β -cyclodextrin into the solution prepared in the step (2), and stirring until the lipoic acid and the hydroxypropyl- β -cyclodextrin are completely dissolved;
(4) adding the water for injection to full dose;
(5) encapsulating the liquid medicine in a brown ampoule;
(6) and (5) sterilizing.
Example 3 animal experiments
First, experiment method
1. Preparation of experimental animal and animal model
Preparation method of mouse model of surgical group (TAC group): selecting SPF male C57BL/6 mouse (purchased from Shanghai Jiesi laboratory animals Co., Ltd.) with week age of 8-10 weeks and body weight of 20-25g, preparing tracheal intubation articles, fixing adhesive tape, etc.; the mouse is placed in an anesthesia closed box, and is quickly fixed on an operation board in a supine manner after the muscle strength disappears; aligning a cold light source to the neck of the mouse, slightly pulling out the tongue of the mouse by using forceps, and under the irradiation of the cold light source, seeing a trachea opening with stronger refractivity consistent with respiratory frequency, rapidly inserting a trachea cannula into an airway, and rapidly inhaling isoflurane again if the mouse has clear-headed signs; the device is connected to an anesthesia respirator, and if intubation is successful, the fluctuation of the thoracic cavity of the mouse along with the frequency of the respirator can be seen; shearing the hair of the chest area of the mouse by using scissors, and disinfecting by using iodophor; cutting skin between two ribs and three ribs on the left edge of the sternum, separating subcutaneous muscle by using hemostatic forceps, cutting a second rib along the left edge of the sternum after the ribs are exposed, placing a chest expander in the chest expander in a proper position, and opening the chest wall; blood can be sucked by using a sterilized cotton swab or a small cotton ball to expose the operation visual field; separating thymus along the middle of bilateral thymus carefully with microscopic forceps, exposing ascending aorta and branch; continuously separating redundant tissues outside the aortic arch and the bifurcation by using the micro forceps to fully expose the aortic arch, the first branch and the second branch; threading No. 5 silk thread through the brachiocephalic trunk and the left common carotid artery by a self-made tool, transversely placing a 27G needle on the aortic arch, and ligating the silk thread on the 27G needle; the needle head is slightly withdrawn; after determining the inactive bleeding, suturing the chest wall and the muscles layer by layer, slightly squeezing the chest wall at the end of closing the chest to remove the gas in the chest cavity as much as possible, and finally suturing the skin; the iodophor disinfects the skin, is connected to a small-sized breathing machine without anesthesia, is put back into the mouse cage after the mouse is completely awake, and can be assisted by a heater to increase the temperature around the mouse so as to accelerate the mouse to wake up;
preparation method of Sham group mouse model: sham group mouse models were only threaded and not ligated, and the remaining procedures were identical to the surgical group (TAC group).
2. Grouping and administration of drugs
The mice are grouped after being tested by ultrasound, so that two groups of baseline horizontal cardiac functions are ensured to be consistent, and four groups are researched: sham + Control group; sham + LA group; TAC + Control group; TAC + LA group. The lipoic acid group is given to the abdominal cavity for injection (100 mg/kg/day, the lipoic acid is lipoic acid injection stock solution, the specification is 12ml:0.3 g); the control group was given the same volume of sterile physiological saline. The mice in each group had normal diet and drinking water, and were administered continuously for 30 days. The body weights of the mice in each group were weighed and recorded daily.
3. Mouse echocardiography assay
Echocardiography was examined at 4 weeks with a probe frequency of 30 MHz. Specifically isoflurane animals, M-mode images were recorded while the heart rate of the mice was maintained at 450-. A B-Mode image of a long axis section beside a sternum and a four-cavity section at the apex of the heart is collected. And taking a short left ventricular axis beside the sternum, and performing 2D ultrasonic left ventricular short axis section, and applying M-type ultrasonic to record the motion condition of the left ventricle at the papillary muscle level. The functional indicators include: left Ventricular Ejection Fraction (LVEF), left ventricular minor axis contraction (LVFS). The heart morphology and function changes of the mice in each group are compared. All measurements were averaged over 5 consecutive cardiac cycles and were performed by 3 experienced technicians.
4. Detection of lung weight to body weight ratio in mice
Mice were sacrificed 4 weeks after drug intervention, lung weight, body weight were weighed, and lung weight/body weight ratio was calculated.
5. Mouse cardiac Dihydroethidium (DHE) staining
Embedding and preparing frozen sections, placing the frozen sections in a wet box to recover the room temperature, washing with PBS for 2 times, fixing with 4% paraformaldehyde for 15min, washing with PBS for 3 times, diluting DHE mother liquor with PBS, dripping PBS on the sections, only dripping PBS on blank control, incubating for 30min at 37 ℃, washing with PBS for 1 time in a dark place, spin-drying redundant liquid on the sections, dripping a proper amount of anti-fluorescence quencher sealing sheet, adjusting exposure parameters according to negative control, randomly photographing each specimen for at least 6 fields of vision, and counting the percentage of red fluorescence in the whole picture according to the difference of fluorescence intensity by Image J.
6. Mouse cardiac ALDH2 activity assay
Mice were sacrificed 4 weeks after drug intervention, 50mg of fresh heart tissue was weighed and tested according to the protocol of ALDH2 activity test kit (tissue acetaldehyde dehydrogenase2 activity colorimetric method quantitative test kit; Shanghai Jimei Gene medicine science and technology Co., Ltd.).
Second, experimental results
1) Echocardiographic results in mice
As shown in fig. 2, the EF% was 11.729% higher (P <0.05) for the TAC + LA group mice than for the TAC + Control group mice; as shown in fig. 3, the TAC + LA group mice were 6.074% higher (P <0.05) than the TAC + Control group mice FS%; compared with mice in a normal saline control group, EF and FS of mice in a Sham group injected with lipoic acid have no difference, and cardiac function indexes of mice in a TAC group are obviously lower than those of mice in the Sham group, as shown in an echocardiogram in figure 4, the cardiac function of the mice in the TAC group injected with the lipoic acid is improved.
2) Lung weight to body weight ratio results in mice
As shown in FIG. 5, the lung weight ratio of the mice in the TAC group was greater than that in the Sham group, and the lung weight ratio of the mice in the TAC + LA group was lower than that in the TAC + Control group (P < 0.05).
3) Mouse cardiac DHE staining results
As shown in fig. 6, the number of DHE-positive cells significantly increased in WT mice after TAC, suggesting that TAC causes increased myocardial ROS production in WT mice. The level of ROS in cardiomyocytes in the TAC + LA group is obviously reduced compared with that in the TAC + Control group, which indicates that the LA can remove the ROS in the myocardium of the mouse after the TAC is removed.
4) Mouse heart ALDH2 activity detection result
As shown in FIG. 7, the activity of cardiac ALDH2 was lower in the TAC group and ALDH2 was higher in the TAC + Control group (P < 0.05).
Third, conclusion of experiment
From the above examples: the cardiac function of the TAC + lipoic acid group is obviously improved compared with that of the TAC + control group; the TAC + lipoic acid group showed a significant reduction in lung weight ratio compared to the TAC + control group. The lipoic acid can treat myocardial damage after pressure overload.
The lipoic acid is widely applied clinically based on strong antioxidant property and rare adverse reactions, the lipoic acid used clinically at present has two forms of intravenous injection and oral capsules, and the lipoic acid indication disease is the paresthesia caused by diabetic peripheral neuropathy at present. Based on research results, the lipoic acid combined with standard drug therapy is expected to obviously improve clinical outcome of patients with myocardial damage after pressure overload, and guide clinical treatment.
Compared with the traditional myocardial damage treatment such as cardiotonic, diuretic and anti-vascular treatment, the lipoic acid with extremely rare adverse reactions is used for treating a patient with myocardial damage after pressure overload, and the lipoic acid can improve the energy metabolism of myocardial mitochondria and inhibit oxidative stress by reducing the activity of ALDH2 in the myocardial mitochondria, thereby playing a role in protecting the myocardial damage after pressure overload and improving the life quality of the patient; the invention develops the new application of the lipoic acid, so that the lipoic acid is better applied; provides a new medicine research direction for the pressure load myocardial damage diseases and has good application prospect.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and additions can be made without departing from the principle of the present invention, and these should also be considered as the protection scope of the present invention.
Claims (3)
1. The application of clinical lipoic acid in preparing a medicine for treating pressure-loaded myocardial injury is characterized in that the lipoic acid is a clinically acceptable pharmaceutical preparation prepared by using the lipoic acid as a main component and adding pharmaceutically acceptable auxiliary materials or auxiliary components to the lipoic acid and plays a role in protecting the myocardial injury after pressure overload by reducing the activity of ALDH2 in myocardial mitochondria, improving the energy metabolism of the myocardial mitochondria and inhibiting oxidative stress.
2. The use of claim 1, wherein the pharmaceutical formulation comprises both oral and injectable formulations.
3. The use of claim 2, wherein the oral formulation is an oral capsule and the injectable formulation is an intravenous solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810788077.8A CN108567775B (en) | 2018-07-18 | 2018-07-18 | Application of lipoic acid in preparation of pharmaceutical composition for treating pressure-loaded myocardial damage |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810788077.8A CN108567775B (en) | 2018-07-18 | 2018-07-18 | Application of lipoic acid in preparation of pharmaceutical composition for treating pressure-loaded myocardial damage |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108567775A CN108567775A (en) | 2018-09-25 |
| CN108567775B true CN108567775B (en) | 2020-02-14 |
Family
ID=63571681
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810788077.8A Active CN108567775B (en) | 2018-07-18 | 2018-07-18 | Application of lipoic acid in preparation of pharmaceutical composition for treating pressure-loaded myocardial damage |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108567775B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113262220A (en) * | 2021-05-13 | 2021-08-17 | 复旦大学附属中山医院 | Application of Bach 2-targeted small-molecule agonist lipoic acid |
| CN113521063B (en) * | 2021-07-12 | 2023-03-10 | 中山大学 | Application of alpha-lipoic acid in resisting fish viral hemorrhagic septicemia virus infection |
| CN114652702B (en) * | 2022-03-23 | 2023-07-07 | 中山大学附属第三医院 | Preparation of lipoic acid-loaded nano material and application of lipoic acid-loaded nano material in acute myocardial infarction diseases |
-
2018
- 2018-07-18 CN CN201810788077.8A patent/CN108567775B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| DL-α-lipoic acid ameliorates cyclophosphamide induced cardiac mitochondrial injury;Mythili Y等;《Toxicology》;20050808;第215卷(第1-2期);第108-114页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108567775A (en) | 2018-09-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108567775B (en) | Application of lipoic acid in preparation of pharmaceutical composition for treating pressure-loaded myocardial damage | |
| EP3505161B1 (en) | Sublingual pharmaceutical composition of edaravone and (+)-2-borneol | |
| WO2015127874A1 (en) | Traditional chinese medicine composition for treating type ii diabetes, and preparation and uses thereof | |
| CN110279699A (en) | With the method for stannsoporfin treatment hyperbilirubinemia | |
| WO2018224016A1 (en) | Use of berberine or derivative thereof in preparing myocardial perfusion imaging agent | |
| CN108042517A (en) | For treating the cysteamine of ischemia injury and/or cystamine | |
| CN110251500A (en) | Use NO(nitric oxide) donor induction arteriogenesis | |
| CN114306304B (en) | Application of 4-hydroxybenzoic acid in preparation of medicine for improving complications of myocardial infarction and medicine | |
| CN111388761B (en) | Application of gastrodin in medical titanium metal use in diabetes environment | |
| JP7335954B2 (en) | Use of bald head saponin B4 in medicine for anti-acute gouty arthritis | |
| CN110664824B (en) | Nutrition supporting agent and preparation method and application thereof | |
| CN115998737B (en) | Application of amodiaquine in preparation of medicine for treating pressure-loaded myocardial injury | |
| CN109223749A (en) | The bromo- 2-(α-Hydroxy pentyl of 5-) medicinal usage of the benzoic acid sodium salt in treatment myocardial hypertrophy and heart failure | |
| CN111481535A (en) | Application of IDHP in preparation of anti-septicemia and myocardial damage drug induced by IDHP | |
| WO2009071098A2 (en) | Use non-human mammal capable of perspiration for determining the effect of hypothermia inducing drugs in humans | |
| AU2019286572A1 (en) | Injectable composition | |
| CN109223766A (en) | Improve the composition and preparation process that microcirculation in human body improves the immunity of the human body | |
| CN113425731B (en) | Medicine for treating myocardial infarction by synergistic stem cells and application thereof | |
| JP6153838B2 (en) | Vascular permeability inhibitor | |
| CN112641783B (en) | Use of ethoxy sanguinarine and related products | |
| RU2784896C2 (en) | Medical use of anemoside b4 against acute gouty arthritis | |
| Gasthuys et al. | Anaesthesia for fluorescein angiography of the ocular fundus in the miniature pig | |
| CN117257803A (en) | Application of lurasidone in preparation of drugs for treating or preventing ischemia/reperfusion injury and cytoprotective drugs | |
| CN115624563A (en) | Application of nicotinamide mononucleotide to preparation of medicine or health-care product for preventing or treating occupational silicosis | |
| CN114288301A (en) | Application of DTQ in preparation of medicine for treating acute myocardial infarction and related product |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20201223 Address after: No.288 Fuchunjiang Road, Southeast Economic Development Zone, Changshu City, Suzhou City, Jiangsu Province Patentee after: JIANGSU WANHE PHARMACEUTICAL Co.,Ltd. Address before: 200032 Shanghai city Xuhui District Fenglin Road No. 180 Patentee before: Zhongshan Hospital, Fudan University |
|
| TR01 | Transfer of patent right |