CN111557949A - Medicine or health product containing hydrogen-rich water and/or NMN and preparation method thereof - Google Patents
Medicine or health product containing hydrogen-rich water and/or NMN and preparation method thereof Download PDFInfo
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/13—Nucleic acids or derivatives thereof
-
- 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
- A61K31/7042—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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
- Y02E60/00—Enabling technologies; Technologies with a potential or indirect contribution to GHG emissions mitigation
- Y02E60/30—Hydrogen technology
- Y02E60/36—Hydrogen production from non-carbon containing sources, e.g. by water electrolysis
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Molecular Biology (AREA)
- Food Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
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Abstract
The invention discloses a medicament or health-care product containing hydrogen-rich water and/or NMN and a preparation method thereof. According to the technical scheme, the intestinal flora is improved by hydrogen-rich water and/or NMN.
Description
Technical Field
The invention relates to the technical field of food and medicine, in particular to a medicine or health-care product containing hydrogen-rich water and/or NMN and a preparation method thereof.
Background
The intestinal tract is an important nutrient absorption and immune organ of a human body, 60% -70% of immune cells of the human body are concentrated in the intestinal tract, the intestinal tract is a main battlefield of body immunity, the intestinal tract health is closely related to intestinal tract flora, the intestinal tract flora and the human body are interdependent and symbiotic to form an intestinal tract microecological system, the intestinal tract microecological system participates in body metabolism, energy balance, immune regulation and the like, the change of the intestinal tract microecological system is related to the occurrence of various diseases, such as constipation, insomnia, halitosis and the like, and long-term toxin accumulation in the body can even cause cancers to threaten the life. Therefore, the balance of the intestinal flora is very important for keeping the intestinal health, can be used as a wind vane for human health, and has profound significance for health by improving the condition of the intestinal flora.
At present, intestinal tract improvement is mostly carried out through living microorganisms such as probiotics and the like, the intestinal tract improvement can play a role in benefiting health of a host, but the intestinal tract improvement has the related problems that thalli are easy to die, the requirement on the storage environment is met and the like, so that certain economic cost is needed for popularization. The method for improving the intestinal environment by compounding the selenium element and the xylo-oligosaccharide is available, but the selenium source is inorganic selenium which is mostly used for drug treatment of patients under extreme conditions, such as keshan disease, Kashin-Beck disease, cancer and the like, and has the advantages of great toxic and side effects, low absorption rate and unobvious effect on improvement of the intestinal environment.
Disclosure of Invention
The invention mainly aims to provide a medicament or health-care product containing hydrogen-rich water and/or NMN and a preparation method thereof, aiming at improving the intestinal flora of organisms.
In order to achieve the above objects, the present invention provides a drug or health product containing hydrogen-rich water and/or NMN for improving intestinal flora.
Optionally, the hydrogen content of the saturated nanoscale soluble hydrogen molecular groups in the selected hydrogen-rich water is 0.50-2.0 mg/L; and/or the presence of a gas in the gas,
the pH range of the hydrogen-rich water is 5.85-6.15; and/or the presence of a gas in the gas,
the oxidation-reduction potential of the hydrogen-rich water is-100 to-150 mV.
Optionally, when the combination of the hydrogen-rich water and the NMN is used, the weight of the combination to dissolve the NMN per 1mL of the hydrogen-rich water is 0.3-2.5 g.
Optionally, when the combination drug is used, the single dose of the combination drug is 0.35-1.5 mg/mL/day.
Optionally, when the hydrogen-rich water is used alone, the single dose of the hydrogen-rich water is 5-25 ml/Kg/day.
Optionally, when the NMN is used alone, the single dose of the NMN is 0.3-1.8 mg/Kg/day.
Optionally, the pharmaceutical or nutraceutical is in liquid form.
Optionally, the medicament or health product is in a gastrointestinal administration form.
The invention also provides a preparation method of the drug or health-care product containing the hydrogen-rich water and/or the NMN, when the combined drug of the hydrogen-rich water and the NMN is used, the NMN is dissolved in the hydrogen-rich water and is uniformly mixed to obtain the combined drug of the hydrogen-rich water and the NMN.
Compared with the prior art, the invention has the following beneficial effects:
the technical scheme of the invention discloses application of a medicine or health-care product containing hydrogen-rich water and/or NMN in improving intestinal flora, and the medicine or health-care product containing hydrogen-rich water and/or NMN can effectively improve the intestinal flora by taking, thereby improving the balance of intestinal microecological systems and reducing various diseases caused by the intestinal flora, such as constipation, insomnia, halitosis and the like. Can be taken for a long time without side effect.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to 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.
In the related art, hydrogen-rich water, i.e., water containing an abundant amount of hydrogen gas, is used. The hydrogen-rich water can effectively prevent and treat various diseases by reducing oxidation reaction and inflammation reaction, such as protection of ischemia reperfusion injury, protection of organ transplantation, treatment of metabolic diseases, treatment of neurodegenerative diseases, treatment of intestinal ulcer inflammation and the like. NMN (nicotinamide mononucleotide) is the product of the nicotinamide phosphoribosyltransferase reaction, one of the key prerequisites for NAD +. In mammals, NMN is produced by nicotinamide under catalysis of Nampt, followed by NMN producing NAD + under catalysis of nicotinamide mononucleotide adenyl transferase. NMN exerts its physiological functions in the human body by conversion to NAD +, such as activating NAD + substrate-dependent Sirt1 (histone deacetylase, also known as sirtuin), regulating cell survival and death, maintaining redox status, and the like. Recent research shows that the NMN in the organism is regulated to have better treatment and repair effects on cardiovascular and cerebrovascular diseases, neurodegenerative diseases, aging degenerative diseases and the like; in addition, NMN has reducing and anti-inflammatory capabilities.
Based on this, the invention provides a medicament or health product containing hydrogen-rich water and/or NMN, which is used for improving the intestinal flora.
The hydrogen-rich water contains nano-scale soluble hydrogen molecular groups, and the hydrogen molecules can participate in signal conduction of different flora in intestinal tract, so that the hydrogen-rich water has anti-inflammatory and anti-oxidation effects, has a certain protection effect on intestinal mucosa, and can promote intestinal tract peristalsis and regulate intestinal tract digestive dysfunction. According to the technical scheme, the improvement of the intestinal flora is realized by hydrogen-rich water with different administration doses.
NMN (nicotinamide mononucleotide) can be converted into NAD in cells, so that Sirt protein 1-7 subtypes are activated, and the NMN has the effects of resisting aging, oxidation and inflammation, protecting intestinal mucosa cells and improving the intestinal environment. According to the technical scheme, the improvement of the intestinal flora is realized by NMN with different administration doses.
Furthermore, the technical scheme of the invention also considers that NMN (nicotinamide mononucleotide) can provide prebiotics for intestinal flora, and when the NMN is compatible with hydrogen-rich water for use, a synergistic anti-inflammatory effect is generated. On one hand, the intestinal mucosa cell protection, the intestinal microenvironment improvement and the growth promotion of probiotics can be improved; on the other hand, the intestinal flora can be regulated and improved by inhibiting the predominant growth of inflammatory intestinal bacteria, so that the occurrence of diseases such as constipation, insomnia, halitosis and the like caused by the imbalance of the intestinal flora is reduced. Therefore, the technical scheme of the invention also aims to realize the improvement of the intestinal flora through the combination drug of the hydrogen-rich water and the NMN.
Optionally, the hydrogen content of the saturated nanoscale soluble hydrogen molecular groups in the selected hydrogen-rich water is 0.50-2.0 mg/L; and/or the presence of a gas in the gas,
the pH range of the hydrogen-rich water is 5.85-6.15; and/or the presence of a gas in the gas,
the oxidation-reduction potential of the hydrogen-rich water is-100 to-150 mV.
Optionally, when the combination of the hydrogen-rich water and the NMN is used, the weight of the combination to dissolve the NMN per 1mL of the hydrogen-rich water is 0.3-2.5 g.
Optionally, when the combination drug is used, the single dose concentration of the combination drug is 0.35-1.5 mg/mL/day.
Alternatively, when the hydrogen-rich water is used alone, the single dose amount of the hydrogen-rich water is. 5-25 ml/Kg/day.
Optionally, when the NMN is used alone, the single dose amount of the NMN is. 0.3-1.8 mg/Kg/day.
Optionally, the pharmaceutical or nutraceutical is in liquid form.
In the embodiment, compared with the administration modes of inhalation and intravenous injection, the administration mode of drinking is safer and more convenient, has higher practicability and popularity, and is suitable for long-term administration. In this regard, the present example provides a pharmaceutical or nutraceutical formulation containing hydrogen-rich water and/or NMN in liquid dosage form.
Specifically, the medicine or the health care product is a gastrointestinal administration dosage form.
The invention also provides a preparation method of the medicine or health-care product containing the hydrogen-rich water and/or NMN. Specifically, when the combined medicine of the hydrogen-rich water and the NMN is used, the NMN is dissolved in the hydrogen-rich water and mixed uniformly to obtain the combined medicine of the hydrogen-rich water and the NMN.
To further illustrate the improvement effect of hydrogen-rich water and/or NMN on intestinal flora in the technical solution of the present invention, the following examples are selected for specific illustration. It is emphasized that the set of embodiments described below is merely a subset of embodiments of the invention and not all embodiments. (the hydrogen-rich water selected in the following example group is supersaturated nanoscale soluble hydrogen molecular group, its hydrogen content is 0.95mg/L, pH value is 5.95, oxidation reduction potential-126.75 mV. NMN selected in the following example group is purchased from Shanghai Pifu biotechnology, Inc.)
Example set 1
HFA mouse model construction
1. Obtaining flora: recruiting a healthy volunteer (female, 25 years old, without digestive tract and metabolic diseases, and without taking antibiotics within 90 days), taking the feces discharged by the volunteer for the first time in the morning, aseptically collecting, weighing within 1 hour under aseptic condition, adding Wikins-Chalgren anaerobic bacteria broth (Oxoid) according to the mass ratio of 1:9(m: V) for dilution, and oscillating and mixing to obtain suspension, namely suspension containing thalli.
2. HFA mouse model: a plurality of sterile KM mice are prepared, the KM mice are 4 weeks old, the weight of the KM mice is 18-22 g, and the KM mice are half male and female respectively. Taking 0.3mL of the suspension containing the thalli in the step 1 per mouse, and performing intragastric lavage on each mouse so as to transfer the flora into the mouse; the culture was carried out for 21 days to allow colonization of the human intestinal flora in the mouse intestine, resulting in a HFA mouse model.
Example group 2
In vivo experiment of hydrogen-rich water on improving intestinal flora
1. HFA mice were housed: 40 HFA mice were randomly assigned to 4 groups of 10 mice each, a normal control group. Performing intragastric administration on each mouse according to the dosage of the hydrogen-rich water shown in the table 1, performing intragastric administration 6 times every day for 30 days continuously, and detecting the intestinal flora content and the intestinal mucosa antibody content of the mouse after 30 days. (free drinking water for mouse in feeding process)
TABLE 1 dosing of hydrogen-rich water for intragastric administration in each example group
| Group of embodiments | Hydrogen rich water dosage (mL/day) |
| Blank group | 0 |
| Example 1 | 4.5 |
| Example 2 | 9 |
| Example 3 | 18 |
2. Detecting the content of each thallus of the intestinal flora of the mice: fixing the mice raised for 30 days by using hydrogen-rich water, cutting the abdomen after disinfecting the skin, and aseptically collecting the cecal contents; placing the contents in a sterile test tube for later use; weighing 1.0g of caecum content in a super clean bench, adding 9mL of sterilized normal saline, mixing and oscillating for 15min to obtain suspension of the caecum content; taking 6 test tubes filled with 9mL of sterilized normal saline, and sequentially diluting the cecal contents according to the concentration gradient until the dilution multiple is 10-5. Specifically, the sample dilution gradient was bifidobacterium (10)-3、10-4、10-5) Lactobacillus (10)-3、10-4、10-5) Enterobacter (10)-3、10-4、10-5) And enterococcus (10)-3、10-4、10-5). Then, 0.2mL of samples at different dilution concentrations were pipetted onto different selection media, plated and cultured, and 3 sets of parallel experiments were performed at each dilution concentration. The culture conditions and identification methods of different intestinal flora are shown in table 2.
TABLE 2 mouse intestinal flora culture and identification method
After the end of the cell culture, the number of viable bacteria was counted by a conventional plate counting method, and the result data shown in Table 3 was obtained.
It is emphasized that all data results were statistically analyzed using SPSS2.0 software, with the results expressed as mean, significance analysis using univariate analysis of variance, and multiple comparisons between groups using LSD test, with P < 0.05 as the difference being statistically significant.
The formula for plate cell count is shown below: (preferably, a plate culture dish with 30-300 bacteria colonies is selected during counting)
Total number of colonies [ lg (CFU/g) ] ═ α × dilution factor/0.1
Wherein alpha is the average colony number of each colony under the same dilution, and each dilution comprises 3 groups of parallel tests;
the total number of cells is expressed as the log of cells per gram of feces.
TABLE 3 bacterial flora and number of cells in the intestinal tract of HFA mice (P < 0.05, P < 0.01, compared to blank)
| Group of | Bifidobacterium | Lactobacillus strain | Enterobacter | Enterococcus |
| Blank group | 8.627±0.521 | 8.551±0.031 | 8.667±0.046 | 7.998±0.042 |
| Example 1 | 8.921±0.432 | 8.398±0.442 | 8.156±0.129 | 7.333±0.0351 |
| Example 2 | 9.086±0.461* | 9.067±0.033* | 7.091±0.095* | 7.719±0.044* |
| Example 3 | 9.824±0.581* | 9.812±0.026* | 7.817±0.827* | 7.843±0.0551* |
As can be seen from table 3 above, at a given hydrogen-rich water dose, the number of cells of bifidobacterium and lactobacillus increases with the increase of the hydrogen-rich water dose, and the number of cells of enterobacter and enterococcus decreases with the increase of the hydrogen-rich water dose; after a certain amount of hydrogen-rich water is added, the number of the enterobacteria and enterococci increases with the increase of the amount of hydrogen-rich water. Wherein, when the hydrogen-rich water dose reaches 9 mL/day, the intestinal bifidobacteria of the mice are increased from 8.627 + -0.521 to 9.086 + -0.461, the lactobacillus is increased from 8.551 + -0.031 to 9.067 + -0.033, the enterobacteria are decreased from 8.667 + -0.046 to 7.091 + -0.095, and the enterococcus is decreased from 7.998 + -0.042 to 7.719 + -0.044. It is stated that hydrogen-rich water can achieve an improvement in the intestinal flora.
3. Detection of mouse intestinal mucosa antibody content: taking the ileum 2 cm at the tail end of the intestinal tract of the mouse, placing the ileum in a sterile beaker, washing the cavity of the ileum by using a phosphate buffer solution in a sterile ice bath until all excrement is removed, taking 1g of 5mL of PBS buffer solution of the ileal mucosa, homogenizing the solution on ice by using a 10mL glass homogenizer, centrifuging the solution for 10min at 1000r/min at 4 ℃, and collecting the supernatant to be placed at-20 ℃ for later use. The content of the secretory immunoglobulin in the ileal mucosa is determined according to the instructions of the slg A kit, and the specific operation is not repeated here. The data results shown in table 4 were obtained.
Table 4 HFA mouse intestinal mucosa slg a content (P < 0.05, P < 0.01 compared to blank)
| Group of | OD450 | slgA(pg/mL) |
| Blank group | 0.0889±0.0029 | 4.865±0.1132 |
| Example 1 | 0.0879±0.0037 | 4.187±0.0069 |
| Example 2 | 0.0989±0.0031* | 5.081±0.0027* |
| Example 3 | 0.1019±0.0038* | 5.199±0.0054* |
As can be seen from table 4 above, at a given hydrogen-rich water dose, the cell concentration in the intestinal tract of the mouse increased with the increase of the hydrogen-rich water dose, and the content of secretory immunoglobulin (slgA) in the intestinal tract of the mouse increased with the increase of the hydrogen-rich water dose. Wherein the OD is the maximum cell concentration reached at a hydrogen-rich water dose of 18 mL/day450The value reaches the maximum of0.1019 ± 0.0038; also, the maximum secreted immunoglobulin (slgA) content was reached, which was 5.199. + -. 0.0054. multidot.pg/mL.
EXAMPLE group 3
In vivo experiment of NMN for improving intestinal flora
1. HFA mice were housed: 40 HFA mice were randomly assigned to 4 groups of 10 mice each, a normal control group. And (3) performing intragastric gavage on each mouse according to the NMN dose shown in the table 5, performing intragastric gavage 6 times every day for 30 days continuously, and detecting the intestinal flora content and the intestinal mucosa antibody content of the mouse after 30 days. (free drinking water for mouse in feeding process)
TABLE 5 intragastric dosing of NMN in the various example groups
| Group of embodiments | NMN dose (g/day) |
| Blank group | 0 |
| Example 1 | 0.25 |
| Example 2 | 0.5 |
| Example 3 | 1.0 |
2. Detecting the content of each thallus of the intestinal flora of the mice: for specific operations, refer to step 2 in embodiment group 2 above, and detailed description is not repeated here. The data results shown in table 6 were obtained.
TABLE 6 bacterial flora and number of cells in the intestinal tract of HFA mice (P < 0.05, P < 0.01, compared to blank)
As can be seen from table 6 above, at a certain NMN dose, the number of bifidobacteria and lactobacilli increased with increasing NMN dose, and the number of enterobacteria and enterococci decreased with increasing NMN dose; after a certain NMN dose, the number of bifidobacteria and lactobacilli decreased with increasing NMN dose, and the number of enterobacteria and enterococci increased with increasing NMN dose. Wherein, when the NMN dose reaches 0.5 g/day, the intestinal bifidobacteria in the mouse are increased from 8.627 + -0.521 to 9.986 + -0.261, the lactobacilli are increased from 8.551 + -0.031 to 9.897 + -0.033, the enterobacteria are decreased from 8.667 + -0.046 to 7.099 + -0.085, and the enterococci are decreased from 7.998 + -0.042 to 7.019 + -0.044. It is demonstrated that NMN can achieve an improvement in intestinal flora.
3. Detection of mouse intestinal mucosa antibody content: for specific operation, refer to step 3 in embodiment group 2, and detailed description is not repeated here. The data results shown in table 7 were obtained.
TABLE 7 HFA mouse intestinal mucosal slg A content (P < 0.05, P < 0.01, compared to blank)
| Group of | OD450 | slgA(pg/mL) |
| Blank group | 0.0889±0.0029 | 4.865±0.1132 |
| Example 4 | 0.0879±0.0045 | 4.779±0.0068 |
| Example 5 | 0.1279±0.0035** | 6.081±0.0065** |
| Example 6 | 0.0996±0.0038* | 5.198±0.0047* |
As can be seen from table 7 above, at a certain NMN dose, the cell concentration in the intestinal tract of the mouse increased with the increase of the NMN dose; after a certain NMN dosage, the thallus concentration decreases with the increase of the NMN dosage. At a certain NMN dose, the content of secreted immunoglobulin (slgA) in the mouse intestinal tract increases with increasing NMN dose; over a certain NMN dose, the secreted immunoglobulin content (slgA) decreased with increasing NMN dose. Wherein the maximum cell concentration is reached at a NMN dose of 0.5 g/day, and the OD is obtained at that time450The value reached a maximum of 0.1279 ± 0.0035 ×; also, the maximum secreted immunoglobulin (slgA) content was reached, which was 6.081 ± 0.0065 × pg/mL.
EXAMPLE group 4
In vivo experiment of combination drug of hydrogen-rich water and NMN on improvement of intestinal flora
1. HFA mice were housed: 40 HFA mice were randomly assigned to 4 groups of 10 mice each, a normal control group. And (3) performing intragastric administration on each mouse according to the dosage of the hydrogen-rich water and NMN combined medicine shown in the table 8, performing intragastric administration 6 times every day for 30 days continuously, and detecting the intestinal flora content and the intestinal mucosa antibody content of the mouse after 30 days. (free drinking water for mouse in feeding process)
TABLE 8 intragastric dosing of the combination of hydrogen-rich water and NMN in each of the example groups
2. Detecting the content of each thallus of the intestinal flora of the mice: for specific operations, refer to step 2 in embodiment group 2 above, and detailed description is not repeated here. The data results shown in table 9 were obtained.
TABLE 9 bacterial flora and number of cells in the gut of HFA mice (P < 0.05, P < 0.01, compared to blank)
| Group of | Bifidobacterium | Lactobacillus strain | Enterobacter | Enterococcus |
| Blank group | 8.627±0.521 | 8.551±0.031 | 8.667±0.046 | 7.998±0.042 |
| Example 4 | 9.086±0.546* | 9.131±0.058* | 8.056±0.068* | 7.203±0.0321* |
| Example 5 | 11.645±0.511** | 11.899±0.263** | 6.019±0.067** | 6.002±0.0552** |
| Example 6 | 9.324±0.654* | 9.229±0.119* | 8.099±0.891* | 7.243±0.0589* |
As can be seen from table 9 above, at a given dose of the combination of NMN and hydrogen-rich water, the number of cells of bifidobacterium and lactobacillus increases with the increase of the dose of the combination of NMN and hydrogen-rich water, and the number of cells of enterobacteria and enterococcus decreases with the increase of the dose of the combination of NMN and hydrogen-rich water; over a certain dosage of the combination of NMN and hydrogen-rich water, the number of the cells of bifidobacterium and lactobacillus decreased with the increase of the dosage of the combination of NMN and hydrogen-rich water, and the number of the cells of enterobacteria and enterococcus increased with the increase of the dosage of the combination of NMN and hydrogen-rich water. Wherein, at a combined drug dose of NMN and hydrogen rich water of 0.5 (g/mL)/day, bifidobacteria in the intestinal tract of mice increased from 8.627 ± 0.521 to 11.645 ± 0.511, lactobacilli increased from 8.551 ± 0.031 to 11.899 ± 0.263, enterobacteria decreased from 8.667 ± 0.046 to 6.019 ± 0.067, and enterococci decreased from 7.998 ± 0.042 to 6.002 ± 0.0552. The combination drug of NMN and hydrogen-rich water can improve the intestinal flora and has obvious effect.
3. Detection of mouse intestinal mucosa antibody content: for specific operation, refer to step 3 in embodiment group 2, and detailed description is not repeated here. The data results shown in table 10 were obtained.
TABLE 10HFA mouse intestinal mucosal slg A content (P < 0.05, P < 0.01, compared to blank)
As can be seen from table 10 above, at a certain dosage of the combination of NMN and hydrogen-rich water, the concentration of the bacteria in the intestinal tract of the mouse increases with the increase of the dosage of the combination of NMN and hydrogen-rich water; after a certain dosage of the combination drug of NMN and hydrogen-rich water is exceeded, the thallus concentration decreases with the increase of the dosage of the combination drug of NMN and hydrogen-rich water. At a certain dosage of the combination of NMN and hydrogen-rich water, the content of secreted immunoglobulin (slgA) in the intestinal tract of the mouse increased with increasing dosage of the combination of NMN and hydrogen-rich water; beyond a certain dosage of the combination of NMN and hydrogen-rich water, the secretory immunoglobulin content (slgA) decreases with increasing dosage of the combination of NMN and hydrogen-rich water. Wherein the maximum cell concentration is reached at a dose of 0.5 (g/mL)/day of the combination of NMN and hydrogen-rich water, at which OD is reached450The value reached a maximum of 0.1483 ± 0.0087 ·; the maximum secreted immunoglobulin (slgA) content was also reached, at which time the secreted immunoglobulin content was 6.346 ± 0.0081 ×.
4. Detection of human intestinal flora: 15 healthy volunteers (female, 25 years old, without digestive tract and metabolic diseases, and without taking antibiotics within 90 days) are recruited, divided into 3 groups, 5 persons in each group, NMN freeze-dried powder is dissolved in hydrogen-rich water with the concentration of 0.37mg/ml, 0.75mg/ml and 1.5mg/ml respectively, each person takes 400ml of NMN hydrogen-rich water each day, the administration is continued for 30 days, feces of the volunteers before and after administration are collected respectively, 10 times of serial dilution is carried out to obtain suspension, and then the suspension is diluted according to the concentration gradient until the dilution multiple is 10-5. Specifically, the sample dilution gradient was bifidobacterium (10)-3、10-4、10-5) Lactobacillus (10)-3、10-4、10-5) Enterobacter (10)-3、10-4、10-5) And enterococcus (10)-3、10-4、10-5). Then, 0.2mL of samples at different dilution concentrations were pipetted onto different selection media, plated and cultured, and 3 sets of parallel experiments were performed at each dilution concentration. The culture conditions and identification methods of different intestinal flora are shown in table 11.
TABLE 11 human intestinal flora culture and identification method
After the completion of the cell culture, the number of viable bacteria was counted by a conventional plate counting method, and the result data shown in Table 12 was obtained.
TABLE 12 bacterial flora and number of cells in human intestinal tract (P < 0.05, P < 0.01, compared to blank)
As can be seen from table 12 above, at a given dose of the combination of NMN and hydrogen-rich water, the number of cells of bifidobacterium and lactobacillus increases with the increase of the dose of the combination of NMN and hydrogen-rich water, and the number of cells of enterobacteria and enterococcus decreases with the increase of the dose of the combination of NMN and hydrogen-rich water; wherein, when the dosage of the NMN and hydrogen-rich water reaches 1.5 (mg/mL)/day, the number of bifidobacteria in human intestinal tract is increased from 7.123 + -0.332 to 9.214 + -0.681, the number of lactobacilli is increased from 6.998 + -0.241 to 9.312 + -0.026, the number of enterobacteria is decreased from 7.603 + -0.323 to 5.997 + -0.527, and the number of coccobacillus is also decreased from 7.383 + -0.243 to 5.893 + -0.0551. The combination drug of NMN and hydrogen-rich water can improve the intestinal flora of human body, and has obvious effect.
The above description is only an alternative embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications and equivalents of the present invention, which are made by the present specification and directly/indirectly applied to other related technical fields within the spirit of the present invention are included in the scope of the present invention.
Claims (9)
1. A medicament or health product comprising hydrogen-rich water and/or NMN for improving the intestinal flora.
2. The drug or health product containing hydrogen-rich water and/or NMN of claim 1, wherein the hydrogen-rich water selected contains saturated nanoscale soluble hydrogen molecular groups with a hydrogen content of 0.50-2.0 mg/L; and/or the presence of a gas in the gas,
the pH range of the hydrogen-rich water is 5.85-6.15; and/or the presence of a gas in the gas,
the oxidation-reduction potential of the hydrogen-rich water is-100 to-150 mV.
3. The pharmaceutical or nutraceutical substance containing hydrogen-rich water and/or NMN according to claim 2, wherein when a combination of said hydrogen-rich water and said NMN is used, the mass of said combination to dissolve said NMN is 0.3-2.5 g per 1mL of said hydrogen-rich water.
4. The drug or health product containing hydrogen-rich water and/or NMN according to claim 3, wherein when the combination drug is used, the single dose amount of the combination drug is 0.35 to 1.5 mg/mL/day.
5. The pharmaceutical or healthcare product containing hydrogen-rich water and/or NMN of claim 2, wherein the single dose of hydrogen-rich water is 5 to 25 ml/Kg/day when the hydrogen-rich water is used alone.
6. The pharmaceutical or nutraceutical containing hydrogen-rich water and/or NMN according to claim 1, wherein the single dose of NMN is 0.3-1.8 mg/Kg/day when the NMN is used alone.
7. The drug or nutraceutical containing hydrogen-rich water and/or NMN according to claim 1, in liquid form.
8. The pharmaceutical or nutraceutical agent containing hydrogen-rich water and/or NMN according to claim 7, in a form for parenteral administration.
9. A method for manufacturing a pharmaceutical or nutraceutical containing hydrogen-rich water and/or NMN, comprising the steps of dissolving the NMN in the hydrogen-rich water and mixing it when using the combination of hydrogen-rich water and NMN to obtain the combination of hydrogen-rich water and NMN.
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