CN107233352A - Application of the NADH in treatment inflammatory pain medicine is prepared - Google Patents
Application of the NADH in treatment inflammatory pain medicine is prepared Download PDFInfo
- Publication number
- CN107233352A CN107233352A CN201710469665.0A CN201710469665A CN107233352A CN 107233352 A CN107233352 A CN 107233352A CN 201710469665 A CN201710469665 A CN 201710469665A CN 107233352 A CN107233352 A CN 107233352A
- Authority
- CN
- China
- Prior art keywords
- nadh
- injection
- application
- inflammatory pain
- medicine
- 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.)
- Pending
Links
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to application of the NADH in treatment inflammatory pain medicine is prepared, being tested by modern pharmacology proves, after ICR mouse injection NADH, there is analgesic activity in the inflammatory pain that formalin or complete Freund's adjuvant are induced, point out NADH to can be used for treatment inflammatory pain.
Description
Technical field
The invention belongs to the application of NADH, and in particular to NADH is in system
Application in standby treatment inflammatory pain medicine.
Background technology
Inflammatory pain is inflammation caused by peripheral tissues' damage as caused by wound, bacterium or virus infection and surgical operation etc.
Disease causes, and is mainly characterized by sensitiveness increase of the damaged tissues to thermostimulation and mechanical stimulus.Inflammatory pain course of disease length and healing
Difficulty, patient in spirit, on body and mind by great pain, had a strong impact on the quality of life of patient, and bring to patient
Heavy financial burden.Because its cause of disease is various, pathogenesis is complicated and causes the incidence of disease high, refractory more to have become clinic
One of problem that medical treatment is most challenged.At present, drug therapy is that control the most frequently used of symptom is also topmost means.According to it
Action character and mechanism can be divided into central nervous system antalgesic and the major class of antipyretic anti-inflammation analgesia medicine two.Central nervous system town
The representative of pain medicine is the activator of opioid recdptor, and it is morphine that it, which represents medicine, but due to the side effect such as additive limit its
Application clinically.Antipyretic and anti-inflammatory antalgesic, also known as non-steroid anti-inflammatory drug, with anti-inflammatory, refrigeration function, wherein analgesia is made
With main portions in periphery, and mechanism of action is mainly by blocking internal cyclooxygenase (COX), so as to suppress prostaglandin
The biosynthesis of (Prostaglandin, PG), weakens the performance of inflammatory reaction and pain effect, it is represented as aspirin, Yin
Diindyl is U.S. pungent etc..But because NSAIDs is to inflammatory pain DeGrain, side effect is more to limit its clinical practice.Cause
This, the cause of disease and pathology that research inflammatory pain is produced are found and exploitation new type analgesic, the heat not only studied as pain medicine
Point and difficult point, and for finally solving this chronic disease, improve the quality of life for the crowd that suffers from have important clinical meaning and
Social effect.
NADH (is abbreviated as NAD+), there is oxidized form (NAD in mammalian body+) and reduction
Type (NADH) two states, oxidized form (NAD+) there is maximal ultraviolet absorption spectrum at 260nm, by various deaminases, from
Receive a hydrogen atom and an electronics in substrate, become reduced form (NADH), there is absorption maximum at 340nm.Nicotinoyl amine gland
Purine dinucleotides participates in a variety of physiological activities such as cellular material metabolism, energy synthesis, cell DNA reparation, to immunity of organism energy
Power plays an important role.Under health status, NADH concentration is stable in human body, maintains every cell normal
Function.Internal NADH concentration determines the process and degree of cell ageing, and concentration declines and can accelerated
The process of cell ageing.NADH is primarily present in yeast cells mitochondria, at present generally from broken
Wall and the method for purification prepare NADH.
The present inventor has found first：NADH has certain analgesic activity to inflammatory pain, is based on
Above-mentioned discovery is by further experiment so as to complete the present invention.
The content of the invention
The present invention provide a kind of NADH prepare treatment inflammatory pain medicine and as activity into
Divide the application prepared in treatment inflammatory pain medicine.
The present invention is achieved through the following technical solutions：
Application of the NADH in treatment inflammatory pain medicine is prepared, described nicotinamide adenine two
The structural formula of nucleotides is：
Application of the described NADH as active component in treatment inflammatory pain medicine is prepared.
Described inflammatory pain is the inflammatory pain that formalin or complete Freund's adjuvant are induced.
When preparing treatment inflammatory pain medicine, described medicine is tablet, capsule, granule, pill, supensoid agent,
Syrup, enteric coated preparations or injection.
It is when described NADH prepares treatment inflammatory pain medicine as injection, nicotinoyl amine gland is fast
Nicotinamide adenine dinucleotide is dissolved in physiological saline, and using intrathecal injection, hypodermic injection, intraperitoneal injection, intravenous injection, concentration is
8mmol/L to 800mmol/L.
Further, the injection volume of intrathecal injection is used for 0.1ul/g-1ul/g；Use hypodermic injection volume for
1ul/g-5ul/g；The injection volume of intraperitoneal injection is used for 1ul/g-200ul/g；The injection volume of intravenous injection is used for 1ul/g-
100ul/g。
NAD in the present invention+By relying on NAD+Deacetylase SIRT1 and SIRT2 participate in regulation formalin and completely
The inflammatory pain that Freund's adjuvant (CFA) induces, and SIRT1 and SIRT2 participate in NAD by different mechanisms+Suppression to inflammatory pain is made
With so that reaching has analgesic effect to inflammatory pain.
Brief description of the drawings
Fig. 1 is that intrathecal injection NADH causes mouse to lick the influence that foot reacts to formalin；
Fig. 2 is the shadow that intrathecal injection NADH causes mouse vola inflammatory reaction to complete Freund's adjuvant
Ring；
Fig. 3 causes the shadow of mouse vola inflammatory reaction for hypodermic injection NADH to complete Freund's adjuvant
Ring.
Embodiment
The present invention is described in detail with specific embodiment below in conjunction with the accompanying drawings.
Embodiment 1
NADH has analgesic activity to inflammatory pain caused by formalin, real below by pharmacodynamics
Test and further illustrate that NADH has therapeutic action in inflammatory pain caused by formalin.
Experimental animal is 20g ICR mouse, purchased from Tongji University's Experimental Animal Center, feeding conditions：Standard feed, room temperature
It is maintained at (24 ± 2) DEG C, humidity 50-60%, animal before experiment, is placed in experimental situation by daily illumination and interlunation each 12h
Adapt to 3 days.
ICR mouse 30 (male, 20g or so) are taken, random point five groups, every group 6, are respectively：Physiological saline group is (intrathecal
Injection, 10ul), morphine group (intrathecal injection, 350nmol/L, 10ul), NADH group (Sigma-
Aldrich, concentration is 8mmol/L, 80mm/L, 800mmol/L, intrathecal injection, 10ul respectively), respectively at after administration
The formalin solution 20ul of subplantar injection 5% after all mouse are right, measures mouse and licks the sufficient time, when record is divided into two immediately
Phase, I phases are 0-10min, and II phases are 10-45min, and experimental result is as shown in figure 1, compared with physiological saline group, in I phases and II phases
In, NADH group (80mmol/L and 800mmol/L) and morphine group (350nmol/L) are reduced when licking sufficient
Between, show that NADH has the effect of anti-inflammatory pain.
Embodiment 2
NADH causes mouse inflammatory pain to have analgesic activity complete Freund's adjuvant, below by drug effect
Experiment is learned to further illustrate.
Take ICR mouse 18 (male, 20g or so), it is random to be divided to two groups, respectively physiological saline group (intrathecal injection,
10ul), NADH group (80mmol/L, intrathecal injection, 10ul).Mouse subplantar injection complete Freund's adjuvant
It is 3rd day, intrathecal respectively to give physiological saline, NADH, using conventional von Frey fiber filaments profit
Measured with up and down methods, 15min, 30min, 45min, 1h, 2h, 3h, 6h mechanical threshold after administration are determined respectively
Value, as a result as shown in Fig. 2 compared with physiological saline group, NADH group is inhibited completely in 15min-3h
Inflammatory pain caused by Freund's adjuvant, shows that NADH has the effect of anti-inflammatory pain.
Embodiment 3
NADH causes mouse inflammatory pain to have analgesic activity complete Freund's adjuvant, below by drug effect
Experiment is learned to further illustrate.
ICR mouse 18 (male, 20g or so) are taken, are divided to two groups at random.Respectively physiological saline group (be subcutaneously injected,
20ul), NADH group (80mmol/L is subcutaneously injected, 20ul).Mouse subplantar injection complete Freund's adjuvant
3rd day, difference sole subcutaneous saline, 80mmol/L NADH, using conventional von
Frey fiber filaments are measured using up and down methods, and 15min, 30min, 45min, 1h, 2h after administration are determined respectively,
3h, 6h mechanical threshold, as a result as shown in figure 3, compared with physiological saline group, NADH group is in 45min
Inflammatory pain caused by complete Freund's adjuvant is inhibited with 1h, shows that NADH has the work of anti-inflammatory pain
With.
Embodiment 4
Take ICR mouse 18 (male, 20g or so), it is random to be divided to two groups, respectively physiological saline group (intrathecal injection,
2ul), NADH group (80mm/L, intrathecal injection, 2ul).Mouse subplantar injection complete Freund's adjuvant the 3rd
My god, intrathecal respectively to give physiological saline, NADH utilizes up using conventional von Frey fiber filaments
And down methods are measured, and 15min, 30min, 45min, 1h, 2h, 3h, 6h mechanical threshold, with life after administration are determined respectively
Reason salt solution group is compared, and NADH group inhibits inflammatory pain caused by complete Freund's adjuvant in 15min-3h,
Show that NADH has the effect of anti-inflammatory pain.
Embodiment 5
The present embodiment takes ICR mouse 30 (male, 20g or so), random point five groups, every group 6, is respectively：Physiology salt
Two groups of water group (hypodermic injection), NADH, concentration is 8mmol/L, 800mmol/L respectively, is pressed respectively
5ul/g and 1ul/g consumption is subcutaneously injected, after administration after all mouse are right subplantar injection 5% formalin solution
20ul, measures mouse and licks the sufficient time, compared with physiological saline group, NADH group is reduced when licking sufficient immediately
Between, show that NADH has the effect of anti-inflammatory pain.
Embodiment 6
ICR mouse 30 (male, 20g or so) are taken, random point five groups, every group 6, are respectively：Physiological saline group, nicotinoyl
Amine adenine-dinucleotide group concentration is 8mmol/L, 800mmol/L respectively, is carried out respectively by 200ul/g and 1ul/g consumption
Intraperitoneal injection, after administration after all mouse are right subplantar injection 5% formalin solution 20ul, when measuring mouse immediately and licking sufficient
Between, compared with physiological saline group, NADH group, which is reduced, licks the sufficient time, shows the core of nicotinamide adenine two
Thuja acid has the effect of anti-inflammatory pain.
Embodiment 7
The present embodiment takes ICR mouse 30 (male, 20g or so), random point five groups, every group 6, is respectively：Physiology salt
Two groups of water group (intravenous injection), NADH, concentration is 8mmol/L, 800mmol/L respectively, is pressed respectively
100ul/g and 1ul/g consumption is injected intravenously, and the formalin of subplantar injection 5% is molten after all mouse are right after administration
Liquid 20ul, measures mouse and licks the sufficient time, compared with physiological saline group, NADH group, which is reduced, licks foot immediately
Time, show that NADH has the effect of anti-inflammatory pain.
Claims (9)
1. application of the NADH in treatment inflammatory pain medicine is prepared, the described core of nicotinamide adenine two
The structural formula of thuja acid is：
2. described in NADH as active component prepare treatment inflammatory pain medicine in application.
3. the application of NADH according to claim 1 or 2, it is characterised in that described inflammatory
The inflammatory pain that pain induces for formalin or complete Freund's adjuvant.
4. the application of NADH according to claim 1 or 2, it is characterised in that preparing treatment
During inflammatory pain medicine, described medicine is tablet, capsule, granule, pill, supensoid agent, syrup, enteric coated preparations or note
Penetrate agent.
5. the application of NADH according to claim 4, it is characterised in that described nicotinoyl amine gland
When purine dinucleotides prepares treatment inflammatory pain medicine as injection, NADH is dissolved in physiology salt
In water, using intrathecal injection, hypodermic injection, intraperitoneal injection or intravenous injection, concentration is 8mmol/L to 800mmol/L.
6. the application of NADH according to claim 5, it is characterised in that described nicotinoyl amine gland
When purine dinucleotides uses intrathecal injection, injection volume is 0.1ul/g-1ul/g.
7. the application of NADH according to claim 5, it is characterised in that described nicotinoyl amine gland
When purine dinucleotides is using being subcutaneously injected, injection volume is 1ul/g-5ul/g.
8. the application of NADH according to claim 5, it is characterised in that described nicotinoyl amine gland
When purine dinucleotides is using intraperitoneal injection, injection volume is 1ul/g-200ul/g.
9. the application of NADH according to claim 5, it is characterised in that described nicotinoyl amine gland
When purine dinucleotides is using intravenous injection, injection volume is 1ul/g-100ul/g.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710469665.0A CN107233352A (en) | 2017-06-20 | 2017-06-20 | Application of the NADH in treatment inflammatory pain medicine is prepared |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710469665.0A CN107233352A (en) | 2017-06-20 | 2017-06-20 | Application of the NADH in treatment inflammatory pain medicine is prepared |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107233352A true CN107233352A (en) | 2017-10-10 |
Family
ID=59986732
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710469665.0A Pending CN107233352A (en) | 2017-06-20 | 2017-06-20 | Application of the NADH in treatment inflammatory pain medicine is prepared |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107233352A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021048129A1 (en) * | 2019-09-09 | 2021-03-18 | Nuvamid Sa | Use of nmn for the prevention and/or treatment of pain, and corresponding compositions |
| WO2021078000A1 (en) * | 2019-10-24 | 2021-04-29 | 泓博元生命科技（深圳）有限公司 | Application of nadh and salt thereof in preparation of drugs or health food for preventing and treating pharyngitis |
| WO2021123388A1 (en) * | 2019-12-20 | 2021-06-24 | Nuvamid Sa | Novel nicotinamide di-nucleotide derivatives and use thereof |
| WO2021180916A1 (en) * | 2020-03-12 | 2021-09-16 | Nuvamid Sa | Use of a nicotinamide mononucleotide or some of its derivatives for the prevention and/or treatment of muscle, ligament or tendon pain induced by physical activity, and corresponding compositions |
| WO2021180915A1 (en) * | 2020-03-12 | 2021-09-16 | Nuvamid Sa | Use of a nicotinamide mononucleotide or some of its derivatives for preventing and/or treating dorsal pain, and corresponding compositions |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016176437A1 (en) * | 2015-04-28 | 2016-11-03 | Newsouth Innovations Pty Limited | Targeting nad+ to treat chemotherapy and radiotherapy induced cognitive impairment, neuropathies and inactivity |
-
2017
- 2017-06-20 CN CN201710469665.0A patent/CN107233352A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016176437A1 (en) * | 2015-04-28 | 2016-11-03 | Newsouth Innovations Pty Limited | Targeting nad+ to treat chemotherapy and radiotherapy induced cognitive impairment, neuropathies and inactivity |
Non-Patent Citations (3)
| Title |
|---|
| HAIJUN， SHAO等: "Spinal SIRT1 Activation Attenuates Neuropathic Pain in Mice", 《PLOS ONE》 * |
| 俞卫锋主编: "《麻醉与复苏新论》", 30 June 2001, 第二军医大学出版社 * |
| 王晓凯等: "SIRT1对大鼠急性脊髓损伤炎症反应的影响", 《中华临床医师杂志（电子版）》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021048129A1 (en) * | 2019-09-09 | 2021-03-18 | Nuvamid Sa | Use of nmn for the prevention and/or treatment of pain, and corresponding compositions |
| CN114423439A (en) * | 2019-09-09 | 2022-04-29 | 努瓦米德股份有限公司 | Use of NMN for preventing and/or treating pain and corresponding composition |
| WO2021078000A1 (en) * | 2019-10-24 | 2021-04-29 | 泓博元生命科技（深圳）有限公司 | Application of nadh and salt thereof in preparation of drugs or health food for preventing and treating pharyngitis |
| WO2021123388A1 (en) * | 2019-12-20 | 2021-06-24 | Nuvamid Sa | Novel nicotinamide di-nucleotide derivatives and use thereof |
| CN115380039A (en) * | 2019-12-20 | 2022-11-22 | 努瓦米德股份有限公司 | Novel nicotinamide dinucleotide derivatives and uses thereof |
| WO2021180916A1 (en) * | 2020-03-12 | 2021-09-16 | Nuvamid Sa | Use of a nicotinamide mononucleotide or some of its derivatives for the prevention and/or treatment of muscle, ligament or tendon pain induced by physical activity, and corresponding compositions |
| WO2021180915A1 (en) * | 2020-03-12 | 2021-09-16 | Nuvamid Sa | Use of a nicotinamide mononucleotide or some of its derivatives for preventing and/or treating dorsal pain, and corresponding compositions |
| FR3108032A1 (en) * | 2020-03-12 | 2021-09-17 | Nuvamid Sa | Use of NMN for the prevention and / or treatment of muscle, ligament or tendon pain induced by physical activity and corresponding compositions |
| FR3108031A1 (en) * | 2020-03-12 | 2021-09-17 | Nuvamid Sa | Use of NMN for the prevention and / or treatment of back pain and corresponding compositions |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107233352A (en) | Application of the NADH in treatment inflammatory pain medicine is prepared | |
| JP2015227341A (en) | Infusion and injection solution of levodopa | |
| US20200206183A1 (en) | Systems, methods, and formulations for treating cancer | |
| CN108025007A (en) | Trimetazidine is preparing the purposes in preventing hepatic medicine | |
| GB2126082A (en) | Pharmaceutical preparations having analgetic and cytostatic activity | |
| WO2021057721A1 (en) | Specific antidotal drug for treating paraquat acute poisoning | |
| CN105748464A (en) | Pharmaceutical composition for treating heart failure with preserved ejection fraction and application of pharmaceutical composition | |
| CN103211141A (en) | Application of anti-hypoxia and anti-fatigue oral composition in health product | |
| CN104784174A (en) | New pharmaceutical use of dexmedetomidine | |
| CN102579420A (en) | Application of leonurine to preparation of medicament for treating 2-type diabetes | |
| EP2932972B1 (en) | New application of catalpol | |
| CN104415023A (en) | Composition for preventing or/and treating insulin resistance and related diseases | |
| CN102639128B (en) | Sulfonamides for the prevention of diabetes | |
| Azendour et al. | Severe amlodipine intoxication treated by hyperinsulinemia euglycemia therapy | |
| CA2305183C (en) | Postsurgical treatment with dichloroacetate | |
| CN104001177B (en) | A kind of compound medicament composition for the treatment of type ii diabetes or metabolism syndrome | |
| Lappa et al. | Successful treatment of a complicated case of neuroleptic malignant syndrome | |
| CN109674790B (en) | Application of thiazolopyrone analogue in preparation of anti-inflammatory drugs | |
| CN102161619B (en) | Ferulic acid Jiangtang compound salt as well as preparation method and application thereof | |
| CN113197884A (en) | Application of alpha-ketobutyric acid in preparation of medicine for preventing and/or treating non-alcoholic fatty liver disease | |
| CN107158021A (en) | NADH is preparing the application for the treatment of cancer pain medicine | |
| CN110314160A (en) | Berbamine prevents and treats the application in medicine for treating diabetic nephropathy in preparation | |
| CN114099511B (en) | Application of liensinine in preparation of medicines for treating pulmonary arterial hypertension | |
| CN109718230A (en) | Application of the salviandic acid A in preparation inhibiting hyperuricemia and anti-gout drugs | |
| CN109464441B (en) | Application of 3-acetamido coumarin in preparing medicine for treating or preventing hyperuricemia and kidney injury |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20171010 |
|
| RJ01 | Rejection of invention patent application after publication |