CN115350167A - Application of idebenone in preparation of uric acid reducing drugs - Google Patents
Application of idebenone in preparation of uric acid reducing drugs Download PDFInfo
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- CN115350167A CN115350167A CN202211202795.5A CN202211202795A CN115350167A CN 115350167 A CN115350167 A CN 115350167A CN 202211202795 A CN202211202795 A CN 202211202795A CN 115350167 A CN115350167 A CN 115350167A
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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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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Abstract
The invention discloses an application of idebenone in preparation of a uric acid reducing drug, and belongs to the technical field of biological medicines. The serum uric acid level, the ROS level, the Bal-2 level and the Bax level of rats in each group are detected by setting a control group, a model group and an experimental group and carrying out hyperuricemia modeling, and the uric acid level, the ROS level and the apoptosis protein Bax level of the rats in the experimental group given idebenone are obviously reduced, and the level of the anti-apoptosis protein Bal-2 is obviously improved, so that the formation of excessive active oxygen can be avoided by the idebenone, the apoptosis protein Bax level is reduced, the level of the anti-apoptosis protein Bal-2 is improved, the apoptosis of cells is reduced, a large amount of nucleotide is avoided, and further serum purine and uric acid are reduced, and the method can be used for treating hyperuricemia.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of idebenone in preparation of a medicament for reducing uric acid.
Background
Hyperuricemia has attracted a wide attention of scholars as the fourth highest following hypertension, hyperglycemia and hyperlipidemia. Uric acid is a product of purine metabolism, and uric acid is produced after purine is metabolized by the liver; high uric acid is a metabolic disease caused by the disturbance of purine metabolism in the human body and the increase of uric acid in blood. Human purines are derived from 20% of food intake and 80% from the catabolic production of nucleic acids by self-cells.
At present, drugs for improving high uric acid mainly comprise three types, the first type is that the activity of purine oxidase is inhibited, and the generation of uric acid is reduced, such as allopurinol and febuxostat; the second is to promote renal excretion of uric acid, such as benzbromarone; the third type is uricase, which oxidizes uric acid into allantoin, which is excreted with urine. The three drugs act on purine produced in vivo, and how to reduce the nucleic acid catabolism of the human body is not involved, so that no drug for reducing uric acid by reducing the nucleic acid catabolism of the human body is available at present.
Idebenone, molecular formula C 19 H 30 O 5 The pharmaceutical composition is mainly used for treating central nervous system degenerative diseases related to oxidative stress clinically, such as Parkinson's disease, alzheimer's disease, multi-infarct dementia, cerebral ischemia, cerebral failure and the like, is also used for treating Friedreich's ataxia, can be used in a cosmetic formula, and has cosmetic efficacies of clearing free radicals, inhibiting lipid peroxidation, inhibiting inflammation, inhibiting DNA damage, photoprotection, relieving pigmentation and the like, but no report that the pharmaceutical composition can reduce uric acid is found.
Disclosure of Invention
In order to overcome the disadvantages of the prior art, the present invention provides an application of idebenone in preparing a medicament for reducing uric acid, wherein uric acid is reduced by reducing the nucleic acid catabolism of human body.
In order to achieve the purpose, the invention adopts the following technical scheme to realize the purpose:
the invention discloses application of idebenone in preparation of a medicament for reducing uric acid.
Preferably, the uric acid lowering drug is a drug that lowers serum reactive oxygen levels.
Preferably, the uric acid reducing drug is a drug for reducing the level of the serum apoptosis protein Bax.
Preferably, the uric acid reducing drug is a drug for increasing the level of a serum anti-apoptotic protein Bal-2.
Preferably, the uric acid lowering drug is a drug for reducing gout.
Preferably, the medicament for reducing uric acid is a medicament for reducing uric acid level of patients with acute and chronic leukemia, polycythemia and hemolytic anemia.
Preferably, the uric acid lowering drug is a drug for preventing uric acid rise after rapid lipid reduction.
Preferably, the dosage form of the uric acid reducing medicine is powder, tablets or capsules prepared by adding medical auxiliary materials into idebenone.
Preferably, idebenone lowers uric acid in rats at a dose of 200mg/kg.
The invention also discloses a composition for reducing uric acid, which takes idebenone as a main active ingredient.
Compared with the prior art, the invention has the following beneficial effects:
the application of idebenone in preparing the uric acid reducing medicine provided by the invention can avoid the formation of excessive active oxygen, reduce the level of apoptosis protein Bax and improve the level of anti-apoptosis protein Bal-2 in the process of reducing uric acid, thereby reducing apoptosis, avoiding the generation of a large amount of nucleotides and further reducing serum purine and uric acid. Because 80% of purine in a human body is generated by nucleic acid catabolism of cells of the human body, idebenone inhibits the generation of purine by reducing the nucleic acid catabolism of the human body, reduces the generation of uric acid from the perspective of reducing substrates, can effectively reduce serum uric acid, and has no hepatorenal toxicity and anaphylactic reaction. In addition, idebenone can be used for secondary hyperuricemia caused by blood system diseases, can also promote renal excretion of uric acid by reducing competitive excretion of lactic acid and uric acid, and is used for treating uric acid increase caused by accumulation of lactic acid in an organism after a large amount of exercise.
Drawings
FIG. 1 is a graph comparing the results of the UA level, ROS level, bal-2 level and Bax level in the serum of rats in the control group, model group and experimental group according to the present invention; wherein, A is the serum UA level of each group of rats, and B is the serum ROS level of each group of rats; c is the Bal-2 level of the serum of each group of rats; d is the serum Bax level of each group of rats.
Detailed Description
In order to make the technical solutions of the present invention better understood, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that the terms "comprises" and "comprising," and any variations thereof, are intended to cover non-exclusive inclusions, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed, but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.
The invention is described in further detail below with reference to the accompanying drawings:
animals: 24 male SD rats, with body mass (220. + -.20) g, were provided by the animal laboratory centre of military medical university of air force.
Reagent: the molding medicine potassium oxonate is purchased from chemical industry Co., ltd of Jinan Zhongke; pyrazinamide was purchased from wuhanding, telecommunications, pharmaceutical, ltd; uric Acid (UA) kit is purchased from Nanjing to build a bioengineering institute; ROS colorimetric kit, bcl-2 ELISA kit and Bax ELISA kit were purchased from Shanghai West Tang Biotech Co., ltd. Idebenone (content is more than or equal to 98.5%) is purchased from Wuhanding Xintong pharmaceutical Co.
The method comprises the following steps: after 1 week of adaptive feeding, rats were randomly divided into a control group, a model group and an experimental group according to body mass, and 8 rats were fed each group. Except for normal rats injected with physiological saline according to the body mass, the other rats are respectively injected with 3% oteracil potassium solution on the back and 4% pyrazinamide solution in the abdominal cavity for 3 weeks continuously 1 time a day and 0.01mL/g, and the content of blood uric acid is detected every week. Starting on day 8 of molding, the rats of the experimental group were gavaged with idebenone at 200mg/kg (dissolved in corn oil) per day, and the rats of the model group and the control group were given corn oil in equal amounts for 14 consecutive days. Fasting for 12h after the last administration, fasting without water prohibition, taking blood from tail vein, centrifuging at 3000r/min for 10min, taking supernatant, and freezing at-70 deg.C for use in biochemical detection. Determining the concentration of ROS in serum by a colorimetric method; enzyme-linked immunosorbent assay detects Bcl-2 and Bax level in serum. Uric acid was detected according to the kit instructions.
Results and analysis:
as can be seen from A in FIG. 1, the serum UA level of the rat in the model group is significantly higher than that of the control group, and has significant difference compared with that of the control group, which indicates that the rat with hyperuricemia is successfully modeled. Compared with the model group, the UA level of the experimental group is obviously reduced, which shows that idebenone can obviously reduce the UA level of the serum of a rat with hyperuricemia.
In B in FIG. 1, the ROS (reactive oxygen species) level in the model rat serum is significantly higher than that in the control group, and is significantly different from that in the control group. Compared with the model group, the ROS level of the experimental group is obviously reduced, which shows that idebenone can obviously reduce the ROS level of the serum of a rat with hyperuricemia.
In C in FIG. 1, the serum Bal-2 level of the model group rat is significantly lower than that of the control group, and is significantly different from that of the control group. Compared with the model group, the experimental group has obviously raised Bal-2 level, which shows that idebenone can obviously improve the level of the anti-apoptotic protein Bal-2 in the serum of the rat with hyperuricemia.
In fig. 1D, the serum Bax level of the model group rat is significantly higher than that of the control group, and is significantly different from that of the control group. Compared with the model group, the experimental group has obviously reduced Bax level, which shows that idebenone can obviously reduce the level of apoptosis protein Bax in the serum of hyperuricemia rat.
The above experiments show that idebenone can reduce the level of uric acid in hyperuricemia rats by reducing the levels of ROS in serum and Bax in the hyperuricemia rats and increasing the level of Bal-2, an anti-apoptotic protein.
The above-mentioned contents are only for illustrating the technical idea of the present invention, and the protection scope of the present invention is not limited thereby, and any modification made on the basis of the technical idea of the present invention falls within the protection scope of the claims of the present invention.
Claims (10)
1. Application of idebenone in preparation of uric acid lowering drugs.
2. The use of claim 1, wherein the uric acid lowering drug is a drug that lowers serum reactive oxygen species.
3. The use of claim 1, wherein the uric acid lowering drug is a drug that reduces the level of the serum apoptotic protein, bax.
4. The use of claim 1, wherein the uric acid lowering drug is a drug that increases serum anti-apoptotic protein Bal-2 levels.
5. The use of claim 1, wherein the uric acid lowering drug is a gout reducing drug.
6. The use of claim 1, wherein the uric acid lowering drug is a drug that lowers uric acid levels in patients with acute and chronic leukemia, polycythemia, and hemolytic anemia.
7. The use of claim 1, wherein the uric acid lowering drug is a drug that prevents uric acid elevation following rapid lipid loss.
8. The use of claim 1, wherein the uric acid lowering drug is in the form of powder, tablet or capsule prepared by adding medical auxiliary materials into idebenone.
9. The use according to claim 1, wherein idebenone lowers uric acid in rats at a dose of 200mg/kg.
10. A uric acid-lowering composition is characterized by taking idebenone as a main active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211202795.5A CN115350167A (en) | 2022-09-29 | 2022-09-29 | Application of idebenone in preparation of uric acid reducing drugs |
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| CN202211202795.5A CN115350167A (en) | 2022-09-29 | 2022-09-29 | Application of idebenone in preparation of uric acid reducing drugs |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110263526A1 (en) * | 2010-04-23 | 2011-10-27 | Piramal Life Sciences Limited | Nitric Oxide Releasing Prodrugs of Therapeutic Agents |
| CN104853753A (en) * | 2012-09-14 | 2015-08-19 | 伊丽莎白·雅顿公司 | Formulations comprising idebenone, n-acetyl-s-farnesyl-l-cysteine and ergothioneine and uses thereof |
| CN109260159A (en) * | 2018-11-29 | 2019-01-25 | 沈阳药科大学 | A kind of pharmaceutical composition and preparation method thereof containing Idebenone |
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2022
- 2022-09-29 CN CN202211202795.5A patent/CN115350167A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110263526A1 (en) * | 2010-04-23 | 2011-10-27 | Piramal Life Sciences Limited | Nitric Oxide Releasing Prodrugs of Therapeutic Agents |
| CN104853753A (en) * | 2012-09-14 | 2015-08-19 | 伊丽莎白·雅顿公司 | Formulations comprising idebenone, n-acetyl-s-farnesyl-l-cysteine and ergothioneine and uses thereof |
| CN109260159A (en) * | 2018-11-29 | 2019-01-25 | 沈阳药科大学 | A kind of pharmaceutical composition and preparation method thereof containing Idebenone |
Non-Patent Citations (5)
| Title |
|---|
| I. SEMSEI，等: "In vitro studies on the OH\" and O2\' free radical scavenger properties of idebenone in chemical systems", 《ARCH. GERONTOL. GERIATR》 * |
| L.M. FADDAH，等: "Biochemical responses of nanosize titanium dioxide in the heart of rats following administration of idepenone and quercetin", 《AFRICAN JOURNAL OF PHARMACY AND PHARMACOLOGY》 * |
| NAYIRA A. ABDEL BAKYA，等: "Nitric oxide pros and cons: The role of l-arginine, a nitric oxide precursor, and idebenone, a coenzyme-Q analogue in ameliorating cerebral hypoxia in rat", 《BRAIN RESEARCH BULLETIN》 * |
| NOUF M.AL-RASHEED，等: "potential impact of quercetin and idebenone against immuno-inflammation and oxidative renal damage induced in rats by titanium dioxide nanoparticles toxicity", 《JOURNAL OF OLEO SCIENCE》 * |
| 贺磊;杨怡;田;邓晶晶;李秀川;裴海峰;杨大春;: "高尿酸通过激活钙蛋白酶加重缺血/缺氧条件下小鼠心肌细胞凋亡", 临床心血管病杂志 * |
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