WO2020244250A1

WO2020244250A1 - Use of composition containing nicotinamide mononucleotides in anti-aging drugs/healthcare products

Info

Publication number: WO2020244250A1
Application number: PCT/CN2020/075629
Authority: WO
Inventors: 陈建生; 张波
Original assignee: 泓博元生命科技（深圳）有限公司
Priority date: 2019-06-06
Filing date: 2020-02-18
Publication date: 2020-12-10
Also published as: CN110237118A

Abstract

Disclosed are a composition containing nicotinamide mononucleotides, a preparation method therefor and the use thereof in the preparation of anti-aging drugs/healthcare products. The raw materials of the composition comprise: nicotinamide mononucleotides, Astragali radix, Ginseng radix et rhizoma, ginsenoside Rb1, coenzyme Q10, puerarin, Eucommiae folium and Astragalus polysaccharides.

Description

Application of composition containing nicotinamide mononucleotide in anti-aging medicine/health product

Technical field

The invention belongs to the research and development field of medicines and health products, and particularly relates to the application of a composition containing nicotinamide mononucleotide in anti-aging medicines/health products.

Background technique

With the continuous improvement of people's living standards, people's desire for health and longevity is becoming stronger and stronger. However, aging is an inevitable law in any life process. It is a biological law that does not depend on the human will. However, it is possible to delay the aging rate and achieve the highest lifespan given by nature. So far, there have been hundreds of theories and hypotheses about the mechanism of aging, such as free radical theory, immune function degradation theory, neuroendocrine theory, protein synthesis error accumulation theory, etc., as well as gene regulation based on molecular level and gene level in recent years. Theory, DNA damage repair theory, mitochondrial damage theory, telomerase theory, etc.

technical problem

In the prior art, although there are various researches on anti-aging mechanisms, the products applied to anti-aging are rare. At present, most of the anti-aging products on the market are combinations of food or Chinese medicine extracts, which have a certain degree of enhancement. The function of human body, but the effect is not ideal, and the anti-aging effect needs to be strengthened. Some anti-aging products use industrial ingredients with strong antioxidant properties in order to achieve a good anti-aging effect, and have quick effects in a short time, but long-term use is extremely harmful to the human body; some anti-aging products add vitamin antioxidants , But this type of product has poor stability.

Therefore, the application of nicotinamide mononucleotide-containing compositions in anti-aging medicines/health products has been developed to solve the problems of anti-aging products in the prior art, which are difficult to take into account the good anti-aging effects and are not harmful to the human body. The technical defect of stable quality has become an urgent problem for those skilled in the art.

Technical solutions

In view of this, the present invention provides the application of a composition containing nicotinamide mononucleotide in anti-aging medicines/health products. No harm and technical defects of stable product quality.

The present invention provides a composition. The raw materials of the composition include: nicotinamide mononucleotide, astragalus, ginseng, ginsenoside Rb1, coenzyme Q10, puerarin, eucommia ulmoides, and scutellarin.

Preferably, based on parts by mass, the raw materials of the composition include: 1 part to 10 parts of nicotinamide mononucleotide, 1 part to 10 parts of astragalus, 1 part to 10 parts of ginseng, and 1 part to 10 parts of ginsenoside Rb1 , 1 part to 10 parts of Coenzyme Q10, 1 part to 10 parts of puerarin, 1 part to 10 parts of Eucommia leaves, and 1 part to 10 parts of Huang Mao polysaccharide.

Preferably, in parts by mass, the raw materials of the composition include 2 to 8 parts of nicotinamide mononucleotide, 5 to 7 parts of astragalus, 2 to 5 parts of ginseng, 3 to 6 parts of ginsenoside Rb1, 1 Parts~5 parts Coenzyme Q10, 6~9 parts Puerarin, 2~5 parts Eucommia ulmoides leaves, 4~10 parts Huang Mao polysaccharides

Preferably, the dosage form of the composition is: oral preparation and/or parenteral administration dosage form.

Preferably, the oral preparation is selected from any one or more of tablets, powders, capsules, granules, pills, suspensions, syrups, mixtures, powders and dripping pills, and the parenteral administration The dosage form is selected from: any one or more of injections, inhalants, patches, suppositories, and ointments. The present invention also provides a preparation method of the composition comprising any one of the above, and the preparation method is:

Step 1: Nicotinamide mononucleotide (NMN), astragalus, ginseng, ginsenoside Rb1, coenzyme Q10, puerarin, eucommia ulmoides leaves, and yellow polysaccharides are dried and then sieved and mixed uniformly to obtain the first product;

Step 2: After the auxiliary materials are dried, they are mixed uniformly and sieved to obtain the second product;

Step 3: After the first product and the second product are dissolved in water, after the first stirring, the temperature is raised and the second stirring is performed to obtain the product.

Preferably, in step 1, the sieved particle size is 60 mesh to 80 mesh;

In step 2, the sieved particle size is 60 mesh to 80 mesh.

Preferably, in step 2, the adjuvant is selected from any one or more of mannitol, microcrystalline cellulose, magnesium stearate, carboxymethyl cellulose and calcium hydrogen phosphate.

Preferably, in step 3, the temperature of the first stirring is 25°C-40°C, the temperature of the second stirring is 50°C, and the time of the second stirring is 1 hour.

The present invention also provides an application of a product comprising the composition described in any one of the above or the product obtained by the preparation method described in any one of the above in anti-aging medicines and/or health products.

Beneficial effect

In summary, the present invention provides a composition. The raw materials of the composition include: nicotinamide mononucleotide, astragalus, ginseng, ginsenoside Rb1, coenzyme Q10, puerarin, eucommia ulmoides and flavone polysaccharide. The present invention also provides a method for preparing the above-mentioned composition. The present invention also provides an application of the above-mentioned composition or the product obtained by the above-mentioned preparation method in anti-aging medicines and/or health products. In the technical scheme provided by the present invention, nicotinamide mononucleotide can activate the body's energy metabolism and improve the body's oxidative stress response. At the same time, it is combined with astragalus, ginseng, ginsenoside Rb1, coenzyme Q10, puerarin, and eucommia The synergistic effect of leaves and Huangmao polysaccharides has a good anti-aging effect; and the structure of each component in the composition is stable, and the corresponding product is not prone to deterioration and damage. At the same time, each component is safe and basically no harm to the human body. reaction. The application of the nicotinamide mononucleotide-containing composition provided by the present invention in anti-aging medicines/health products solves the problem of anti-aging products in the prior art that are difficult to have good anti-aging effects, no harm to the human body, and product quality Stable technical defects.

Description of the drawings

In order to more clearly describe the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings that need to be used in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only These are some embodiments of the present application. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative work.

among them:

Figure 1 is a schematic diagram of the results of the weight change of the mice in the control group, the NMN group and the product 1 group during the 6-month test period (n=10 mice/group).

Figure 2 is a schematic diagram of the results of the food intake of mice in the control group, the NMN group and the product 1 group during the 6-month test period (n=10 mice/group).

Figure 3 is a schematic diagram of the results of the water intake of mice in the control group, the NMN group and the product 1 group during the 6-month test period (n=10 mice/group).

Figure 4 is a schematic diagram of the results of fat content and lean meat content of mice in the control group, the NMN group and the product 1 group after being tested for 6 months (n=10 mice/group).

Figure 5 is a schematic diagram of the results of oxygen consumption (VO ₂ ) of the mice in the control group, the NMN group and the product 1 group after being tested for 6 months.

Figure 6 is a schematic diagram showing the results of energy expenditure (EE) and respiratory entropy (RQ) of mice in the control group, NMN group and product 1 group for 6 months (n=10 mice/group).

Figure 7 is a schematic diagram of the results of mouse respiratory entropy (RQ) after taking the control group, the NMN group and the product 1 group for 6 months (n=10 mice/group).

Embodiments of the invention

The technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the protection scope of this application.

The present invention provides the application of a composition containing nicotinamide mononucleotide in anti-aging medicines/health products, which is used to solve the problem of anti-aging products in the prior art that are difficult to take into account good anti-aging effects and are not harmful to the human body. Technical defects with stable quality.

In order to explain the present invention in more detail, the application of the nicotinamide mononucleotide-containing composition provided by the present invention in anti-aging medicines/health products will be specifically described below in conjunction with examples.

The present invention provides a composition comprising: nicotinamide mononucleotide (NMN), astragalus, ginseng, ginsenoside Rb1, coenzyme Q10, puerarin, eucommia leaves, and scutellarin. The application of the nicotinamide mononucleotide-containing composition provided by the present invention in anti-aging medicines/health products solves the problem of anti-aging products in the prior art that are difficult to have good anti-aging effects, no harm to the human body, and product quality Stable technical defects.

NMN is the precursor of NAD+. After entering the cell, NMN becomes an important coenzyme NAD+ that participates in many reactions in the human body. In a variety of cellular metabolic reactions, NAD+ plays an important role and is an important support for cells to maintain vitality. But as we age, NAD+ levels will continue to decrease, and cell metabolism will also be affected. After NMN is administered to elderly mice, it is beneficial to promote their systemic metabolism, and has positive effects on skeletal muscle, liver function, bone density, eye function, insulin sensitivity, immune function, etc.; supplementation of NMN helps the elderly maintain Cell energy, relieve the symptoms of chronic diseases related to aging.

At the same time, in the composition provided by the present invention, astragalus and ginseng can increase the content of human myocardial cells lactate dehydrogenase and succinate dehydrogenase to varying degrees, and ginseng can increase the content of cAMP in myocardial cells, especially ginsenosides Rb1 can promote rabbit chondrocyte proliferation, enhance SOD activity, and maintain the expression of type II collagen.

Furthermore, the puerarin in the composition can promote the proliferation and differentiation of osteoblasts, increase alkaline phosphatase activity, and increase the expression of OPGmRNA; Eucommia ulmoides leaf extract has a promoting effect on the proliferation of osteoblasts and the secretion of ALP enzyme protein. It can significantly regulate bone metabolism; Coenzyme Q10 is an important member and intermediate link of the hydrogen transmitter of the respiratory chain in the cell mitochondria, can promote the production of ATP, is an activator of energy metabolism, lipid antioxidant, free radical scavenger and membrane stabilization It is an activator that nourishes cells and improves cell metabolism; Huangmao polysaccharide is extracted from the traditional Chinese medicine Huang Miao, it can promote hematopoiesis, has immune enhancement and regulation effects, and has the effects of enhancing cell metabolism, strengthening the heart and anti-aging.

In the technical scheme provided by the present invention, specific ingredients and specific ratios are adopted, the formula is reasonable, the compatibility is appropriate, conforms to the theory of combining traditional Chinese medicine and modern medicine, is convenient to use, has good absorption effects, and has no adverse or side effects; It is verified that it can effectively reduce free radicals in the body and maintain the level of active oxygen, thereby improving cell damage caused by electromagnetic radiation of mobile phones.

Example 1

This embodiment is a specific embodiment for preparing product 1.

Nicotinamide mononucleotide, astragalus, ginseng, ginsenoside Rb1, coenzyme Q10, puerarin, eucommia ulmoides and yellow polysaccharides were dried and passed through a 60-80 mesh sieve and mixed uniformly to obtain the first product;

After drying, the auxiliary materials are mixed uniformly and passed through a 60-80 mesh sieve to obtain the second product; in this example, the auxiliary material is mannitol.

After the first product and the second product are dissolved in water, stir for the first time at 25 ℃ ~ 40 ℃, stir evenly and then raise the temperature, and stir for the second time at 50 ℃. After stirring for 1 hour, the formulation is tablet product 1; In this embodiment, the formulation process used is a conventional formulation process well known to those skilled in the art, and will not be repeated here.

In this embodiment, in the first product, the amount of each raw material is: 2 g nicotinamide mononucleotide, 7 g astragalus, 4 g ginseng, 1 g ginsenoside Rb1, 3 g coenzyme Q10, 9 g puerarin, 4 g Eucommia leaves and 7 g Huang Mao polysaccharide.

Example 2

This embodiment is a specific embodiment for preparing product 2.

After drying, the auxiliary materials are mixed uniformly and passed through a 60-80 mesh sieve to obtain the second product; in this example, the auxiliary material is microcrystalline cellulose.

After the first product and the second product are dissolved in water, stir for the first time at 25 ℃ ~ 40 ℃, stir evenly and then raise the temperature, and stir for the second time at 50 ℃. After stirring for 1 hour, the formulation will give pill product 2; In the examples, the formulation process used is a conventional formulation process well known to those skilled in the art, and will not be repeated here.

In this embodiment, in the first product, the amount of each raw material is: 10 g nicotinamide mononucleotide, 1 g astragalus, 2 g ginseng, 3 g ginsenoside Rb1, 10 g coenzyme Q10, 1 g puerarin, 2 g Eucommia leaves and 4 g Huang Mao polysaccharide.

Example 3

This embodiment is a specific embodiment for preparing product 3.

After drying, the auxiliary materials are mixed uniformly and passed through a 60-80 mesh sieve to obtain the second product; in this embodiment, the auxiliary material is magnesium stearate.

After the first product and the second product are dissolved in water, they are stirred for the first time at 25 ℃ ~ 40 ℃, stirred evenly and then heated up, and stirred for the second time at 50 ℃. After stirring for 1 hour, the preparation is granular product 3; In this embodiment, the formulation process used is a conventional formulation process well known to those skilled in the art, and will not be repeated here.

In this embodiment, in the first product, the amount of each raw material is: 8 g nicotinamide mononucleotide, 5 g astragalus, 10 g ginseng, 6 g ginsenoside Rb1, 1 g coenzyme Q10, 10 g puerarin, 5 g Eucommia leaves and 8 g Huang Mao polysaccharide.

Example 4

This embodiment is a specific embodiment for preparing product 4.

After drying, the auxiliary materials are mixed uniformly and passed through a 60-80 mesh sieve to obtain the second product; in this example, the auxiliary material is carboxymethyl cellulose.

After the first product and the second product are dissolved in water, they are stirred for the first time at 25 ℃ ~ 40 ℃, after stirring, the temperature is raised, and the second time is stirred at 50 ℃. After stirring for 1 hour, the preparation is made into capsule product 4; In this embodiment, the formulation process used is a conventional formulation process well known to those skilled in the art, and will not be repeated here.

In this embodiment, in the first product, the amount of each raw material is: 1 g nicotinamide mononucleotide, 10 g astragalus, 5 g ginseng, 10 g ginsenoside Rb1, 5 g coenzyme Q10, 6 g puerarin, 1 g Eucommia leaves and 1 g Huang Mao polysaccharide.

Example 5

This embodiment is a specific embodiment for preparing product 5.

After drying, the auxiliary materials are mixed uniformly and passed through a 60-80 mesh sieve to obtain the second product; in this example, the auxiliary material is dibasic calcium phosphate.

After the first product and the second product are dissolved in water, stir for the first time at 25 ℃ ~ 40 ℃, stir evenly, raise the temperature, and stir for the second time at 50 ℃. After stirring for 1 hour, the formulation obtains water product 5; In this embodiment, the formulation process used is a conventional formulation process well known to those skilled in the art, and will not be repeated here.

In this embodiment, in the first product, the amount of each raw material is: 6 g nicotinamide mononucleotide, 6 g astragalus, 1 g ginseng, 4 g ginsenoside Rb1, 2 g coenzyme Q10, 8 g puerarin, 10 g Eucommia leaves and 10 g Huang Mao polysaccharide.

Example 6

6.1 Animal handling

C57BL/6 male mice were purchased from 3 months to 4 months old. All mice were bred adaptively in the animal room for 2 weeks, and the light was adjusted according to the 12-hour day rhythm. During the breeding period, the mice can freely enter water and eat, and the breeding environment temperature is always maintained at 20 ℃-22 ℃, and the relative humidity is 50%-60%.

After a 2-week adaptation period, the experiment was carried out, and the mice were divided into a control group, an experimental group and an NMN composition group: the control group mice continued to drink normal water, and the experimental group mice received the drink containing the product 1 prepared by the present invention Water (target dose of 150 mg/kg/day) for 6 consecutive months, and NMN composition group received drinking water containing NMN composition (target dose of 150 mg/kg/day) for 6 consecutive months. Measure your weight at the same time every week. Measure food and water intake for 7 consecutive days at the same time every month.

6.2 Metabolic analysis

Six months after the mice were supplemented with product 1/NMN, the Oxymax indirect calorimetry system (Columbus Instruments, Columbus, OH) was used to measure metabolic parameters. Before data measurement, the mice were individually adapted to a temperature of 22 ℃-24 ℃, 12 hours light/12 hours dark cycle environment for 24 hours.

Oxymax system VO ₂ and VCO ₂ ratios are set as follows: air flow 0.7 liters/min; sample flow rate 0.6 liters/min; calibration time 5 min; measurement time 4 min. The system is calibrated according to the standard gas mixture, measuring the consumed O2 (VO ₂ , ml/kg/hr) and the produced CO ₂ (VCO ₂ , ml/kg/hr).

Assess oxygen consumption (VO ₂ ) and respiratory entropy (VCO ₂ /VO ₂ ratio) within 24 hours. Energy consumption (EE) is calculated based on the calorific value produced by O ₂ (3.815+1.232x breathing entropy) and the volume consumed by O ₂ .

6.3 Experimental results

It can be concluded from Figure 1 that supplementation of NMN can inhibit the weight gain caused by age-related growth in mice, and the linear dose-dependent effect is statistically significant at all time points at 6 months (P<0.05).

It can be drawn from Figure 4 that compared to the control group, NMN group and product 1 group of mice, the average of the normalized weight loss percentages were 4% and 9%, respectively; at 6 months, the NMN group and the composition group of the present invention Compared with the control group, the amount of fat decreased and the amount of lean meat increased.

Please refer to Figures 2 and 3, as the age of the mice increases, compared with control mice, mice in the NMN group and product 1 group can maintain a higher level of food and water consumption in a dose-dependent manner; and , The mice in the product 1 group gained faster and better weight than the NMN group.

Throughout the experimental period, there was no statistical difference in the survival rate between the control group, the NMN group and the product 1 group of mice. No significant differences in causes of death (including urinary tract obstruction, thrombosis, and myocardial infarction) were observed between the groups. It shows that the product 1 prepared by the technical scheme provided by the present invention can significantly inhibit age-related weight gain in a dose-dependent manner in conventionally fed mice through administration, and there is no significant increase during the entire 6-month intervention period. Side effects.

6.4 Determination of oxygen consumption, energy consumption and respiratory entropy

During the experiment, compared with the control group, the experimental group and the NMN group had more food intake but lower body weight. At the 6th month, the oxygen consumption, energy consumption and respiratory entropy of each group of mice were measured.

From Figure 5 and Figure 6, it can be concluded that the oxygen consumption and energy consumption of the NMN group and product 1 group increased significantly, and the oxygen consumption and energy consumption of the product 1 group were higher than those of the NMN group; it can be derived from Figure 7 , NMN group and product 1 group respiration entropy decreased significantly.

The above results show that: the mice taking NMN group and product 1 convert their main energy source from glucose to fatty acid, which can further show that taking NMN group and product 1 group has a significant preventive effect on mice age-related energy metabolism damage , So as to play an effective anti-aging effect.

Products 2 to 5 repeat the above experiments in this embodiment, and similar experimental results are obtained, which will not be repeated here.

The above are only the preferred embodiments of the present invention. It should be pointed out that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made, and these improvements and modifications are also It should be regarded as the protection scope of the present invention.

Claims

A composition, characterized in that the raw materials of the composition include: nicotinamide mononucleotide, astragalus, ginseng, ginsenoside Rb1, coenzyme Q10, puerarin, eucommia ulmoides leaf, and scutellarin.
The composition according to claim 1, wherein, in parts by mass, the raw materials of the composition comprise: 1 part to 10 parts of nicotinamide mononucleotide, 1 part to 10 parts of astragalus, 1 part to 10 parts 1 part of ginseng, 1 part to 10 parts of ginsenoside Rb1, 1 part to 10 parts of Coenzyme Q10, 1 part to 10 parts of puerarin, 1 part to 10 parts of Eucommia ulmoides leaf, and 1 part to 10 parts of Huang Mao polysaccharide.
The composition according to claim 2, characterized in that, in parts by mass, the raw materials of the composition include 2 to 8 parts of nicotinamide mononucleotide, 5 to 7 parts of astragalus, 2 to 5 parts of Ginseng, 3 parts to 6 parts of ginsenoside Rb1, 1 part to 5 parts of Coenzyme Q10, 6 parts to 9 parts of puerarin, 2 parts to 5 parts of Eucommia leaves, and 4 parts to 10 parts of Huang Mao polysaccharide.
The composition according to any one of claims 1 to 3, wherein the dosage form of the composition is: oral preparation and/or parenteral administration dosage form.
The composition according to claim 4, wherein the oral preparation is selected from the group consisting of: tablets, powders, capsules, granules, pills, suspensions, syrups, mixtures, powders and dripping pills One or more, and the parenteral administration dosage form is selected from any one or more of injections, inhalants, patches, suppositories, and ointments.
A preparation method comprising the composition according to any one of claims 1 to 5, characterized in that the preparation method is:

Step 1: Nicotinamide mononucleotide, astragalus, ginseng, ginsenoside Rb1, coenzyme Q10, puerarin, eucommia ulmoides, and yellow polysaccharides are dried and then sieved and mixed uniformly to obtain the first product;

Step 2: After the auxiliary materials are dried, they are mixed uniformly and sieved to obtain the second product;

Step 3: After the first product and the second product are dissolved in water, after the first stirring, the temperature is raised and the second stirring is performed to obtain the product.
The preparation method according to claim 6, wherein in step 1, the sieved particle size is 60 mesh to 80 mesh;

In step 2, the sieved particle size is 60 mesh to 80 mesh.
The preparation method according to claim 6, characterized in that, in step 2, the adjuvant is selected from any one of mannitol, microcrystalline cellulose, magnesium stearate, carboxymethyl cellulose and calcium hydrogen phosphate Kind or more.
The preparation method according to claim 6, wherein in step 3, the temperature of the first stirring is 25°C-40°C, the temperature of the second stirring is 50°C, and the temperature of the second stirring is 50°C. The stirring time is 1 hour.
An application of the composition according to any one of claims 1 to 5 or the product obtained by the preparation method according to any one of claims 6 to 9 in anti-aging medicines and/or health products.