CN109674808A - β-nicotinamide mononucleotide or its precursor are preparing the purposes delayed in lung senescence drug - Google Patents
β-nicotinamide mononucleotide or its precursor are preparing the purposes delayed in lung senescence drug Download PDFInfo
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- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
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- A—HUMAN NECESSITIES
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- A61P11/00—Drugs for disorders of the respiratory system
Abstract
The invention belongs to biomedicine technical fields, and in particular to a kind of β-nicotinamide mononucleotide or its precursor are preparing the purposes delayed in lung senescence drug.The prior art there are no the research that the lung function of the age-related property of supplement of β-nicotinamide mononucleotide or its precursor reduces, the present invention constructs lung aging model, discovery addition β-nicotinamide mononucleotide or its precursor can delay lung's aging for the first time, especially alveolar epithelial cells aging provides the purposes of β-nicotinamide mononucleotide or its precursor in the drug that preparation delays lung aging.The present invention provides a kind of new approach, also provides a kind of new treatment foundation to prevent or treating the associated lung disease as caused by lung aging, have broad prospects to delay lung aging, lung function being delayed to reduce.
Description
Technical field
The invention belongs to biomedicine technical fields, and in particular to prepared by a kind of β-nicotinamide mononucleotide or its precursor
Delay the purposes in lung senescence drug.
Background technique
Body gradually appears cell, tissue and organ physiological function, resistivity and adaptive faculty with the increase at age
The phenomenon that Deng failing.Lung function is gradually decreased with the increase of organismic age, so as to cause the hair of the relevant lung disease of aging
Raw rate increases, such as: lung cancer, chronic structural lung disease, chronic fibrosis of lung etc..And the process that these organ dysfunctions reduce is
Generation based on cell ageing, i.e. cell ageing are the bases of body aging.
With in the increase body cell of organismic age significant change first is that NAD+Horizontal reduction, thus will
NAD+The horizontal relevant lung disease of reduction and aging connects.NAD+NADH can be formed, is that a kind of reducing agent and electronics supply
Body participates in different cell processes, including silicosis oxidant and anti-oxidant system, participates in mitochondrial oxidative metabolism process, thin as ensuring
Born of the same parents' survival and adjusting energetic supersession, the signaling molecule of cell repair and circadian rhythm, to intracellular a variety of enzymes in the form of coenzyme
Physiological function generate adjustment effect, including deacetylase and poly-ADP- ribose polymerase (PARP).Work as NAD+Horizontal drop
When low, will lead to this intracellular serial procedures dysfunction, so as to cause and NAD+Body various physiological processes are participated in, are belonged to
Intracellular a variety of enzymes play the coenzyme of physiological function, such as SIRTs family, participate in the signal of intracellular multi-signal approach
The adjusting etc. of substance.Work as NAD+When level reduces, intracellular level of inflammation is caused to increase, mitochondria dysfunction and some
Column depend on NAD+Enzyme dysfunction, cell occurs metabolic disorder, and leads to the damage etc. of DNA, eventually lead to cell and walk
To aging.
Intrapulmonary cell category is various, and one of most important cell is exactly alveolar epithelial cells, and alveolar epithelial cells is main
It is the chief component of blood gas barrier positioned at the terminal end of respiratory tract, is divided into I type and II type, I type accounts for overall 96%, II type
It is 4%.Alveolar type II cells have certain stemness (differentiation capability), and can secrete alveolar surfactant, maintain alveolar
Surface tension.The main function that alveolar epithelial cells is played in intrapulmonary are as follows: barrier, gas exchanges, immunological regulation.Alveolar epithelium is thin
Born of the same parents constitute 99% surface area of lung, and the aging of the cell is the main reason for causing lung function to reduce with the increase at age.
β-nicotinamide mononucleotide (NMN, nicotinamide mononucleotide) and β-niacinamide ribose (NR,
Nicotinamide riboside), belong to the precursor substance of NAD, this kind of NAD is provided+Precursor substance have prevent and treat
Effect is alleviated age-dependent pathology and morbid state, and the benefit of metabolism, the secretion including promoting insulin, and is promoted
Into the sensibility of insulin, enhance the activity of SIRTs family, reduce the expression of inflammation-related gene, reduces oxidative stress, and
The rhythm and pace of moving things for improving heart reduces the inflammation in the adipose tissue of age related, and improves systemic insulin sensitivity.
In recent years for NMN supplement research it is more and more, although the pharmacokinetic pathways that it is occurred also be not it is very clear,
Existing research the result shows that, NMN can promote mitochondrial function, including promote mitochondria oxidative phosphorylation ability, increase line
The lipid oxidation etc. of plastochondria.The function of promoting nervous system, human-subject test and memory including improving Alzheimer's disease.It is right
Acute kidney injury has protective effect.The study found that the age is bigger more sensitive to NMN.Verified is that the addition of NMN may be used also
It include skeletal muscle, liver, cardiac muscle, eyes etc. to improve the function of the mitochondria in tissue.
But it yet there are no the lung function about the supplement of β-nicotinamide mononucleotide or its precursor to age related
Reduction and lung disease between correlativity research report.
Summary of the invention
The technical problem to be solved in the present invention are as follows: the prior art there are no β-nicotinamide mononucleotide or the supplement of its precursor
The research that the lung function of age-related property reduces.
The technical solution of present invention solution above-mentioned technical problem are as follows: provide a kind of β-nicotinamide mononucleotide or its precursor
Delay the purposes in lung senescence drug in preparation.
Wherein, in such use, the β-nicotinamide mononucleotide precursor is β-niacinamide ribose.
Wherein, in such use, the lung aging that delays is to delay alveolar aging.
Further, in such use, the alveolar aging that delays is to delay alveolar epithelial cells aging.
Further, in such use, the alveolar epithelial cells aging is naturally-aged or stress caused aging.
Further, in such use, it is described stress caused by aging include that smoking, radiotherapy, chemicals are controlled
It treats, chronic lung disease or asthma stimulate caused aging.
Wherein, in such use, the drug is added using β-nicotinamide mononucleotide or its precursor as active constituent
The auxiliary material or complementary ingredient pharmaceutically received, the preparation being prepared.
Further, the preparation is oral preparation.
Further, per unit oral preparation contains β-nicotinamide mononucleotide or its precursor 20-1000mg.
Further, the oral preparation includes solid pharmaceutical preparation, liquid preparation or suspension preparation.
Further, the solid pharmaceutical preparation includes capsule, tablet, pill, powder or granule.
Further, the liquid preparation includes lotion, solution, suspension, syrup or tincture.
The invention has the benefit that
Present invention firstly discovers that addition β-nicotinamide mononucleotide or its precursor can delay lung's aging, further study
It was found that the aging of β-nicotinamide mononucleotide or its precursor and alveolar epithelial cells is closely bound up, β-niacinamide list is thus provided
The purposes of nucleotide or its precursor in the drug that preparation delays lung aging.The present invention is to delay lung aging, lung function is delayed to drop
It is low to provide a kind of new approach, also a kind of new treatment is provided to prevent or treating the associated lung disease as caused by lung aging
Foundation has broad prospects.
Detailed description of the invention
Fig. 1 show different mouse SA-Gal, P16 and P21 (× 40) immunohistochemical staining figures.
Fig. 2, which show NMN, improves the alveolar epithelial cells aging figure of bleomycin induced；A is to observe under inverted microscope
SA- β gal dyes (× 40)；B is 3 groups of multiple holes of every group of setting, randomly selects 5 visuals field and carries out statistical analysis (P < 0.05).
Fig. 3, which show NMN, improves the injury of lungs of bleomycin induction.A is after the bleomycin of addition NMN is handled 21 days
The improvement of lung appearance and lung weight.
Fig. 4 show HE dyeing and SA- β-Gal, P16, P21 immunohistochemical staining (* 40) at bleomycin
It is carried out on the freezing lung sections of the mouse of reason.Every group has 3 mouse.It is (P < 0.05) for statistical analysis to randomly choose 5 visual angles.
Fig. 5 is the lung inflammation that NMN alleviates bleomycin induction in mouse.A is to be filled by Flow cytometry alveolar
The infiltration of macrophage in washing lotion, neutrophil leucocyte and monocyte changes.B: in flow cytomery bronchoalveolar lavage fluid
Macrophage, in the bleomycin group of addition NMN, macrophage is reduced, and every group 3 (P < 0.05)；(b): flow cytometer inspection
Survey BAL fluid in neutrophil leucocyte, addition NMN bleomycin group, Neutrophilic granulocytopenia, every group 3
Rat (P < 0.001)；(d): the monocyte in flow cytomery BAL fluid (BALF), in addition NMN
Bleomycin group, monocyte reduce, every group of 3 groups (P < 0.05).
Fig. 6 is the lung inflammation that NMN alleviates bleomycin induction in mouse.Pass through Flow cytometry lung group shown in A
Knit middle macrophage, the infiltration of neutrophil leucocyte and monocyte.B: flow cytomery lung tissue macrophage is adding
The bleomycin group of NMN, macrophage are reduced, and every group 3 (P < 0.05)；C: flow cytomery lung tissue neutrality grain is thin
Born of the same parents, in the bleomycin group of addition NMN, Neutrophilic granulocytopenia, every group of 3 rats (P < 0.001)；D: flow cytometry is used for
The monocyte in lung tissue is detected, in the bleomycin group of addition NMN, monocyte is reduced, and every group 3 (P < 0.001).
The alveolar epithelial cells aging of bleomycin induction is alleviated in the addition of NMN.
Fig. 7, which show NMN, improves the alveolar epithelial cells aging figure of bleomycin induction.A is under SA- inverted microscope
β-gal dyes (× 40)；B is 3 groups of multiple holes of every group of setting, randomly selects 5 visuals field and carries out statistical analysis；(P<0.05).
Specific embodiment
The present invention provides a kind of β-nicotinamide mononucleotides or its precursor to delay the purposes in lung senescence drug in preparation.
Wherein, in such use, the β-nicotinamide mononucleotide precursor is β-niacinamide ribose.
Wherein, in such use, the lung aging that delays is to delay alveolar aging.
Further, in such use, the alveolar aging that delays is to delay alveolar epithelial cells aging.
In order to inquire into whether NMN can alleviate lung's aging, the present invention is with naturally-aged and bleomycin processing aging
Model pays close attention to addition NMN later to the improvement result of cell ageing.Research is found: in alveolar epithelial cells naturally-aged
The senescent phenotypes of alveolar epithelial cells can be effectively relieved in addition with NMN in the model of bleomycin induction aging.
Explanation will be further explained to a specific embodiment of the invention by embodiment below, but do not indicated this
The protection scope of invention is limited in range described in embodiment.
Influence research of 1 β of the embodiment-nicotinamide mononucleotide to mouse alveolar epithelial cells
1. material
1.1 SPF grades of experimental animal C57BL/6 mouse (female, the 8-10 month or 6-8 week old, < 28~30g and 19~21g),
It buys in Beijing Vital River Experimental Animals Technology Co., Ltd., raises in SPF grades of animal houses.
1.2 experimental drug fetal calf serums, PRMI1640 (gibico), SA- β-Gal staining kit (green skies biology skill
Art company), calf serum, culture dish, physiological saline, dehydrated alcohol, antibody, (Abcam company, the U.S.), sa- β-gal are anti-
Body (Beta galactosidase Antibody, Proteintech company, the U.S.), niacinamide ribose (nicotinamide
Riboside, Shanghai Han Xiang company), FITC label mouse fluorescence secondary antibody (AbD Serotec company, the U.S.), (U.S. IL-6
CST company), TNF-α (CST company, the U.S.), IL-1 β (CST company, the U.S.).(show prestige trade in Guangzhou is limited for haematoxylin dye liquor
Company), H2DCF-DA (Sigma Co., USA), sodium chloride (Chengdu Ke Long chemical reagent factory), the wet box, (U.S. Golgistop
BD Biosciences company), remaining reagent is ordinary commercial products.
1.3 instrument and equipment Milli-Q Integral pure water meters (French Millipore company), (middle section's U.S. water chestnut is low for refrigerator
Warm science and technology responsibility Co., Ltd, Siemens Co., Ltd, Qingdao HaiEr Co., Ltd), baking oven (German Binder company),
Superclean bench (Japanese Sanyo company), constant incubator (Japanese Sanyo company), AUW1200 assay balance (Japan
Shimadzu company), high-pressure sterilizing pot (Japanese Sanyo company), ice machine (Japanese Sanyo company), ultra low temperature freezer (Japan
Sanyo company), recirculated water bath (German Julabo Labortechnik GmbH company), centrifuge (U.S. Thermo
Fisher Scientific company), Ai Sen NovoExpress flow cytometer (Chinese Essen Biology company), just to set fluorescence aobvious
Micro mirror (Eclipse80i, Japanese Nikon company), inverted fluorescence microscope (Japanese Nikon company), wet box (Jiangsu Province, China south
Logical city Wei Ning experiment equipment Co., Ltd), micro-wave oven (company of middle Guomei), microplate reader (Shanghai Thermo-Fisher company),
Refrigerator (middle section's U.S. water chestnut low temperature science and technology responsibility Co., Ltd, Siemens (China) Co Ltd, Qingdao HaiEr Co., Ltd),
Baking oven (German Binder company), superclean bench (Japanese Sanyo company), constant incubator (Japanese Sanyo company),
AUW1200 assay balance (Shimadzu, Japan), high-pressure sterilizing pot (Japanese Sanyo company), ice machine (Japanese Sanyo
Company), ultra low temperature freezer (Japanese Sanyo company), recirculated water bath (German Julabo Labortechnik GmbH company),
Centrifuge (Thermo Fisher Scientific company, the U.S.), Ai Sen NovoExpress flow cytometer (Chinese Ai Sensheng
Object company), ice machine (Japanese Sanyo company), electric drying oven with forced convection (Shanghai Yiheng Scientific Instruments Co., Ltd), balance
(Shimadzu, Japan), PCR instrument (Bio-Rad company, the U.S.).
2. experimental method
2.1 aging models establish experiment and are divided into 4 groups, respectively young control group, aged control, old age drinking-water
It adds NMN group and NMN group is added in old stomach-filling (every group is chosen 10 mouse respectively)；Its person in middle and old age drinking-water addition NMN group is first led to
It spends one week and mouse amount of drinking water is observed, then determine each additive amount.Each confluent is 400ml, and addition NMN dosage is 6g,
A water is changed within every 4 days, the processing time is 2 months.Stomach-filling group mouse, daily set time carry out stomach-filling processing, and dosage is
500mg/kg。
2.2 lung primary epithelial cells extraction processs extract the primary alveolar cell of lung of 6-8 weeks C57/BL6 mouse, use import
1640 and 10% fetal calf serum, add 1% penicillin and streptomysin culture.De- neck puts to death mouse, impregnates 3 points with 75% alcohol
Clock.Next it is operated on sterile platform, takes out mouse lung tissue, cleaned with physiological saline, eye scissors shred into unqualified shape, add
IV Collagenase Type 5-6ml, the 37 DEG C of digestion 1h of 1mg/ml use the screen to filtrate later, are centrifuged (800rap/3min), outwell supernatant,
Add 3-5ml erythrocyte cracked liquid, mix, stands 3min.It is centrifuged (800rap/3min), outwells supernatant, culture medium is resuspended, is layered on
It in 10cm ware, is placed in incubator, overnight, changes liquid within second day.The primary alveolar cell of naturally-aged, passage to the 4th generation when
It waits, carries out NMN addition processing, change a not good liquor within every two days, until passage to the 7th, 8 generations, carry out morphology with passage property aging group
Compare, until discovery is obviously improved.
2.3 experimental group cell experiments are divided into 3 groups, every group of 3 holes, it may be assumed that 1. non-aging group, 2. aging group, 3. aging+
NMN (500um/ml) group；Zoopery is divided into 4 groups, every group 10, it may be assumed that 1. young group (6-8 weeks), 2. aging group (8-10 month)
3. aging+drinking-water NMN (6g, 400ml, 4 day), 4. aging+stomach-filling NMN (500mg/kg.day).NMN concentration by preliminary experiment with
SA- β-Gal stained positive rate is selected for screening index.
3. detection method
3.1SA- β-Gal, which is dyed, cultivates lung primary epithelial cells in 24 orifice plates, cell culture fluid is absorbed, with PBS or HBSS
Washing 1 time, is added 1 milliliter of beta galactosidase dyeing fixer, and room temperature fixes 15 minutes.Absorb cell fixer, with PBS or
HBSS is washed cell 3 times, every time 3 minutes.PBS or HBSS is absorbed, 1 milliliter of dyeing working fluid is added in every hole.Use polypropylene
(polypropylene) dyeing working fluid is prepared to specifications.37 DEG C, without being incubated overnight in carbon dioxide incubator, are used
24 orifice plate of parafilm ParafilmTM prevents from evaporating.Fluorescence microscopy is just being set to take pictures under the microscope.
The lung sections of deparaffinization and rehydration are exposed to 3%H by 3.2 immunohistochemical stainings2O2Methanol solution in
30 minutes, with the quenching endogenous peroxidase activity after taking out antigen using citrate buffer (0.01M, pH 6.0).
Pass through the non-specific binding for being incubated for slice 30 minutes come blocking antibody and histotomy with 5% Normal Goat Serum in PBS.
Lung tissue section is incubated overnight with the titre of 1:500 at 4 DEG C with primary p16 (Abcam) or p21 (Abcam) antibody.Washing
Afterwards, slice is incubated 1 hour together with the biotinylated anti-rabbit Ig (servicebio) of secondary antibody, and use DAB (DAKO) as
Peroxidase substrate.Then haematoxylin redyeing is carried out before checking under an optical microscope.
3.3 flow cytometry
The single cell suspension prepared is taken, fixes 30min with the paraformaldehyde of 1%-3%；It is washed twice with PBS, in abandoning
Clearly；Cell membrane punching, adds 1%Triton-X-100 (Triton X-100) 200ul, room temperature 10-30min；It is floated with PBS
It washes twice；First antibody, room temperature 30-60min is added；Twice with PBS rinsing, secondary antibody is added, room temperature 20min is protected from light；Use PBS
Rinsing twice, abandons supernatant；It is resuspended and uses 200ulPBS, upper machine testing.
4. statistical method
It is examined by double tail student t and ANOVA analyzes data.Statistical analysis is carried out using GraphPad Prism 6；
If mean difference is too small between heterogeneity of variance or group can be used rank sum test.Think statistically significant in p < 0.05.
5, experimental result: lung's aging of NMN alleviation natural aging mice
Beta galactosidase is widely used as universally recognized aging index, and senile cell is along with proliferative capacity
Reduction, mainly due to expression of cyclin kinase inhibitor (cell cycle inhibitors) expression increase.Embodiment 1
The study found that the NMN stomach-filling period relevant with the SA- β-Gal of drinking-water NMN addition group and aging inhibits albumen (p16, p23)
It is substantially reduced relative to control group (as shown in Figure 1).As it can be seen that, the addition of NMN can improve mouse lung aging.
2 NMN of embodiment delays primary alveolar epithelial cells aging
In vivo on the basis of EXPERIMENTAL EXAMPLE 1, we have further probed into NMN for the direct work of alveolar epithelial cells
With whether investigation NMN can alleviate the replicative senescence of alveolar epithelial cells and the aging of environmental stimuli induction.
Experimentation is as follows:
The primary alveolar epithelial cells of separating mouse carries out in vitro culture, and when passage is to the 7th, 8 generation, aging table occurs in cell
Type, i.e. cellular morphology significantly become larger, and are rounded, and nucleus increases as fried egg sample, and ability of cell proliferation is significantly reduced.Cell declines
Old reason first is that NAD+ reduce, oxidation-antioxidation is unbalance, oxidative stress increase caused by irritability aging.Carefully
Born of the same parents add NMN (dosage 500um/ml) when passage is to 4 generation, compare until passage is not added with group to 7,8 Dai Shiyu, cell
Senescent phenotypes are obviously improved.The relevant SA- β-Gal dyeing of detection discovery aging is in NMN addition group and is not added with the 7th of group the, 8 generations
(Fig. 2) is significantly reduced in alveolar epithelial cells.
The result of embodiment 2 is as it can be seen that the replicability that the primary alveolar epithelial cells of lung can be effectively relieved in the addition of NMN declines
Always.
3 NMN of embodiment alleviates the mouse alveolar aging of bleomycin induction
Whether NMN can alleviate the replicative senescence caused by alveolar increases with the age, stress be caused then can alleviate
Alveolar aging.Bleomycin belongs to glycopeptide antibiotic family member, has effective antitumour activity.Its main secondary work of poison
With being to cause pulmonary fibrosis, and main mechanism is to lead to unstable and ROS the generation of genome.
Now studies have found that bleomycin inducing lung fibrosis is based on leading to alveolar epithelial cells aging, to damage
Hurt the regeneration of alveolar epithelial cells.There are cell ageings during lung fiber, and by inducing cell apoptosis, it is possible to reduce aging
The secretion of related SASP, and the label of extracellular matrix fibrosis is reduced, while increasing the label of alveolar epithelial cells.Cause
This, we are model using bleomycin induction lung primary epithelial cells aging, and whether investigation NMN, which can alleviate bleomycin, lures
The alveolar epithelial cells aging led.
According to existing research, bleomycin dose 2mg/kg, at the 21st day of processing mouse inducing lung fibrosis, aging
Relevant SA- β-Gal dyeing is the most significant.Therefore, by tongue larynx instillation, start while giving the processing of mouse bleomycin
NMN stomach-filling, dosage are 500mg/kg/ days.The stomach-filling time is 21 days.Later, Aging marker detection is carried out.It was found that NMN adds
The appearance of group mouse lung is added to significantly improve, and weight significantly reduces (Fig. 3).Carry out Immunohistochemical detection, discovery NMN addition
The relevant SA- β-Gal of group aging and aging relevant period inhibit protein expression to substantially reduce (Fig. 4) then, have carried out lung
The flow cytometer detection of irrigating solution (Fig. 5) and lung tissue (Fig. 6) are steeped, the inflammatory cell of discovery NMN addition group substantially reduces (Fig. 5 and figure
6).According to the experimental results: the addition of NMN can be obviously improved the alveolar epithelial cells aging of bleomycin induction and reduce lung
Inflammation change.
4 NMN of embodiment alleviates the mouse alveolar epithelial cells aging of bleomycin induction
Equally, on the basis of the In vivo model of bleomycin induction alveolar aging.In vitro, it is handled using bleomycin
NMN is added in alveolar epithelial cells aging, investigates whether NMN can be effectively relieved alveolar epithelial cells aging.We have found that NMN
The alveolar epithelial cells aging of bleomycin induction can be effectively relieved.Bleomycin dose are as follows: 5ug/ml, induction time 3
It, bed board three days again later.Bleomycin processing cell adds NMN (500um/ml) simultaneously.We have found that bleomycin induces
Alveolar epithelial cells is expressed the relevant betagalactosidase activity of aging and is increased, and handles through NMN, the aging phase of bleomycin induction
It closes betagalactosidase activity and is substantially reduced (Fig. 7 A is morphological observation), the cell of the betagalactosidase activity positive is carried out
It counts, is expressed as % positive cell (Fig. 7 B), it has been found that handled through NMN, the aging correlation beta galactose glycosides of bleomycin induction
Enzyme positive cell significantly reduces (Fig. 4 B).In short, the lung primary cell of bleomycin induction can be effectively relieved in the addition of NMN
Aging.
By embodiment 1-4 it is found that in vivo and in vitro, the alveolar epithelial cells of identical passage number is in NMN supplementation group than non-
Significant reduction in supplementation group.Except the alveolar epithelial cells aging group of bleomycin induction and the aging NMN of bleomycin induction add
It is outer to enter group, the alveolar epithelial cells of aging also significantly reduces.It has been found that NMN reduces what bleomycin in mouse lung induced
Inflammation.Statistics indicate that NMN can effectively mitigate the duplication of internal and external alveolar epithelial cells and the aging of stress-induced.
It is will provide prevention and treatment method come chronic lung disease relevant to aging and injury of lungs as caused by outside stimulus.
NAD+ is reduced in vivo with aging, it is considered to be the important regulatory factor of age-dependent pathologic process.NAD+
Intracorporal various physiological activities are participated in, are glycolysis, the crucial confactor and cell of tricarboxylic acid cycle and oxidative phosphorylation
In various redox reactions.The anti-aging effects of NAD+ replenishers are confirmed in many tissues and organ, such as satellite
Cell, angiogenesis and skeletal muscle cardiac muscle.NMN and NR can be used as nutritional additive to increase the level of internal NAD+, thus anti-
The only generation of aging.
Cause the factor of cell ageing very much, including oxidative stress, mitochondria dysfunction etc..Studies have shown that rich next mould
Element is to the toxicity of cell mainly since Genomic instability and oxidative stress increase.Supplement NMN can not only reduce intracellular
Oxidative stress can also reduce the cell function damage of oxidative stress induction, including genetic instability, improve mitochondria
Function increases the activity of NAD+ dependent enzyme (such as SIRT family).
In short, the long-term addition NMN of research discovery can effectively improve the duplication of alveolar epithelial cells in vivo and in vitro
With the aging of stress-induced.The dietary supplements or drug of NMN may be prevention and reduction aging associated pulmonary diseases and irritability lung
The new effective ways of one kind of damage.
Claims (10)
1. β-nicotinamide mononucleotide or its precursor delay the purposes in lung senescence drug in preparation.
2. purposes according to claim 1, it is characterised in that: the β-nicotinamide mononucleotide precursor is β-niacinamide
Ribose.
3. purposes according to claim 1 or 2, it is characterised in that: the lung aging that delays is to delay alveolar aging.
4. purposes according to claim 1-3, it is characterised in that: the alveolar aging that delays is to delay alveolar
Epithelial cell aging.
5. purposes according to claim 1-4, it is characterised in that: the alveolar epithelial cells aging is nature
Aging stress caused aging.
6. purposes according to claim 1-5, it is characterised in that: it is described stress caused by aging include inhaling
Aging caused by cigarette, radiotherapy, chemotherapy, chronic lung disease or asthma stimulate.
7. purposes according to claim 1-6, it is characterised in that: the drug is with β-niacinamide monokaryon glycosides
Acid or its precursor are active constituent, and the auxiliary material or complementary ingredient pharmaceutically received, the preparation being prepared is added.
8. purposes according to claim 1-7, it is characterised in that: the preparation is oral preparation.
9. purposes according to claim 1-8, it is characterised in that: per unit oral preparation contains β-niacinamide list
Nucleotide or its precursor 20-1000mg.
10. -9 described in any item purposes according to claim 1, it is characterised in that: the oral preparation include solid pharmaceutical preparation,
Liquid preparation or suspension preparation.
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| CN114796255A (en) * | 2022-03-30 | 2022-07-29 | 深圳市旷逸生物科技有限公司 | Application of nicotinamide mononucleotide in protecting liver from being damaged |
| CN115837022A (en) * | 2023-02-20 | 2023-03-24 | 中山大学附属第八医院（深圳福田） | Application of 1,2,4 triazolo 4,3-B pyridazine derivative in preparation of anti-aging drugs |
| CN115837022B (en) * | 2023-02-20 | 2023-04-25 | 中山大学附属第八医院（深圳福田） | Application of 1,2, 4-triazolo 4,3-B pyridazine derivative in preparation of anti-aging drugs |
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