CN116210907A - Composition containing beta-nicotinamide mononucleotide and nervonic acid and application thereof - Google Patents

Composition containing beta-nicotinamide mononucleotide and nervonic acid and application thereof Download PDF

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CN116210907A
CN116210907A CN202111470104.5A CN202111470104A CN116210907A CN 116210907 A CN116210907 A CN 116210907A CN 202111470104 A CN202111470104 A CN 202111470104A CN 116210907 A CN116210907 A CN 116210907A
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nervonic acid
nicotinamide mononucleotide
beta
composition
sleep
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谢永美
魏于全
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Chengdu Chuanyu Jianwei Biotechnology Co ltd
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Chengdu Chuanyu Jianwei Biotechnology Co ltd
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Priority to PCT/CN2022/134272 priority patent/WO2023098581A1/en
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    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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    • 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
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • 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
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
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    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
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    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Abstract

The invention relates to a composition containing beta-nicotinamide mononucleotide and nervonic acid and application thereof, belonging to the technical field of medical health care. The technical problem solved by the invention is to provide a composition containing beta-nicotinamide mononucleotide and nervonic acid, which can improve sleep. The active ingredients of the composition consist of the following components in percentage by weight: 20-70% of beta-nicotinamide mononucleotide and the balance of nervonic acid. The beta-nicotinamide mononucleotide and the nervonic acid are compounded according to a specific proportion, can complement each other, and are synergistic, so that the sleeping can be well improved, and the beta-nicotinamide mononucleotide and the nervonic acid can be applied to the fields of foods, health-care products or medicines and the like.

Description

Composition containing beta-nicotinamide mononucleotide and nervonic acid and application thereof
Technical Field
The invention relates to a composition containing beta-nicotinamide mononucleotide and nervonic acid and application thereof, belonging to the technical field of medical health care.
Background
Sleep is an indispensable physiological phenomenon for humans. Sleep takes up approximately 1/3 of the life of a person, and the sleeping quality is closely related to the health of the person. The most easily caused bad sleeping is the disorder of the biological clock, thereby causing the immunity to be reduced, the metabolism to be disturbed and the dyspepsia to cause a series of diseases such as obesity, respiratory system, cardiovascular and cerebrovascular diseases, senile dementia, anxiety and the like.
According to the world health organization report, 27% of people worldwide have sleep problems. The data of the '2021 sports and sleep white book' issued by the China sleep research institute and other institutions show that more than 3 hundred million people have sleep disorder in China. The sleep deficiency becomes a major kill for human health, and causes serious trouble to life, study and work of people. Currently, drugs for improving sleep disorders mainly include benzodiazepines, non-benzodiazepines, melatonin, and antidepressants. However, these drugs are addictive or have side effects such as cognitive impairment. In addition, there are many functional foods on the market that claim to have sleep improvement, but most of them are not good. Therefore, development of products with good therapeutic effects and little side effects for improving sleep is urgently required.
Beta-nicotinamide mononucleotide (beta-Nicotinamide mononucleotide, abbreviated NMN) is a natural bioactive nucleotide which is widely used in human body and various foods and is coenzyme I-NAD + Key intermediates of (a). The research shows that NMN has the effects of recovering the activity of neuron cells, improving energy metabolism, regulating immune response and the like.
NMN is used for improving sleep, and has limited effect and needs to be further improved.
Disclosure of Invention
The technical problem solved by the invention is to provide a composition containing beta-nicotinamide mononucleotide and nervonic acid, which can improve sleep.
The invention relates to a composition containing beta-nicotinamide mononucleotide and nervonic acid, which comprises the following active ingredients in percentage by weight: 20-70% of beta-nicotinamide mononucleotide and the balance of nervonic acid.
In some embodiments of the invention, the active ingredient of the composition comprising β -nicotinamide mononucleotide and a nervonic acid consists of the following weight percentages: 30-50% of beta-nicotinamide mononucleotide and the balance of nervonic acid.
In a preferred embodiment, the active ingredient of the composition comprising β -nicotinamide mononucleotide and a nervonic acid consists of the following weight percentages: 30-40% of beta-nicotinamide mononucleotide and the balance of nervonic acid.
In a more preferred embodiment, the active ingredient of the composition comprising β -nicotinamide mononucleotide and a nervonic acid consists of the following weight percentages: beta-nicotinamide mononucleotide 40% and the rest is nervonic acid.
In some embodiments of the invention, the composition further comprises an adjuvant.
In some embodiments of the invention, the composition is in the form of a granule, tablet, capsule, pill, paste, beverage, solid beverage, or biscuit.
The invention also provides application of the composition containing the beta-nicotinamide mononucleotide and the nervonic acid in preparing a food, a health-care product or a medicine for improving sleep.
The composition containing the beta-nicotinamide mononucleotide and the nervonic acid can improve sleep and is applied to foods, health-care products or medicines.
Compared with the prior art, the invention has the following beneficial effects:
the invention adopts the beta-nicotinamide mononucleotide and the nervonic acid to be compounded, and the beta-nicotinamide mononucleotide and the nervonic acid are synergistic, so that the sleeping can be well improved, the beta-nicotinamide mononucleotide and the nervonic acid can be applied to the fields of foods, health-care products or medicines and the like, and a new way is provided for improving the sleeping.
Detailed Description
The invention relates to a composition containing beta-nicotinamide mononucleotide and nervonic acid, which comprises the following active ingredients in percentage by weight: 20-70% of beta-nicotinamide mononucleotide and the balance of nervonic acid.
Nervonic acid is a core natural component of brain nerve cells and nerve tissues, and research shows that the nervonic acid has the efficacy of promoting the repair and regeneration of damaged nerve tissues and is an essential 'higher nutrient' for the growth, regeneration and maintenance of nerve cells, especially brain cells, optic nerve cells and peripheral nerve cells. The research of the invention discovers that the beta-nicotinamide mononucleotide and the nervonic acid are compounded according to a specific proportion, and the beta-nicotinamide mononucleotide and the nervonic acid can complement each other, and are synergistic, so that the sleeping can be well improved, and the beta-nicotinamide mononucleotide and the nervonic acid can be applied to the fields of foods, health-care products or medicines and the like.
In some embodiments of the invention, the active ingredient of the composition comprising β -nicotinamide mononucleotide and a nervonic acid consists of the following weight percentages: 30-50% of beta-nicotinamide mononucleotide and the balance of nervonic acid.
In a preferred embodiment, the active ingredient of the composition comprising β -nicotinamide mononucleotide and a nervonic acid consists of the following weight percentages: 30-40% of beta-nicotinamide mononucleotide and the balance of nervonic acid.
In a more preferred embodiment, the active ingredient of the composition comprising β -nicotinamide mononucleotide and a nervonic acid consists of the following weight percentages: beta-nicotinamide mononucleotide 40% and the rest is nervonic acid.
In addition to the active ingredient, in some embodiments of the invention, the composition further comprises an adjuvant. Adjuvants commonly used in the art are suitable for use in the present invention.
Various auxiliary materials can be added according to the prior art to prepare the composition into various dosage forms according to the product requirement. In some embodiments of the invention, the composition is in the form of a granule, tablet, capsule, pill, paste, beverage, solid beverage, or biscuit.
The compositions of the invention comprising beta-nicotinamide mononucleotide and a nervonic acid can be prepared using conventional methods. In one embodiment of the invention, the composition comprising the beta-nicotinamide mononucleotide and the nervonic acid can be prepared by uniformly mixing the beta-nicotinamide mononucleotide and the nervonic acid in proportion.
The composition containing the beta-nicotinamide mononucleotide and the nervonic acid can improve sleep, and can be applied to preparing sleep improving foods, health care products or medicines.
The following describes the invention in more detail with reference to examples, which are not intended to limit the invention thereto.
Example 1
This example provides a composition having a total mass of 20g. 4g of beta-nicotinamide mononucleotide and 16g of nervonic acid are weighed and uniformly mixed.
Example 2
This example provides a composition having a total mass of 20g. 6g of beta-nicotinamide mononucleotide and 14g of nervonic acid are weighed and uniformly mixed.
Example 3
This example provides a composition having a total mass of 20g. 8g of beta-nicotinamide mononucleotide and 12g of nervonic acid are weighed and uniformly mixed.
Example 4
This example provides a composition having a total mass of 20g. 10g of beta-nicotinamide mononucleotide and 10g of nervonic acid are weighed and uniformly mixed.
Example 5
This example provides a composition having a total mass of 20g. 12g of beta-nicotinamide mononucleotide and 8g of nervonic acid are weighed and uniformly mixed.
Example 6
This example provides a composition having a total mass of 20g. 14g of beta-nicotinamide mononucleotide and 6g of nervonic acid are weighed and uniformly mixed.
Example 7
This example provides a composition having a total mass of 20g. 16g of beta-nicotinamide mononucleotide and 4g of nervonic acid are weighed and uniformly mixed.
Test example 1 composition prescription screening test
1. Experimental materials
Beta-nicotinamide mononucleotide and nervonic acid are self-made by the research and development center of Chengdu Chuan-Jian vitamin science and technology Co., ltd, and the HPLC content is more than 98%.
2. Experimental animal
132 healthy SPF-class female BALB/c mice, 6-8 weeks old, and 18-22 g in weight, provided by Sichuan university laboratory animal center, laboratory animal production license number SYXK (Sichuan) 2018-185, eligibility number: 00116042.
3. experimental method
The mice were randomly divided into 11 groups of 12, each of which was a blank control group, the positive drug diazepam as control (2 mg/kg, BW), beta-nicotinamide mononucleotide (200 mg/kg, BW), the nervonic acid group (200 mg/kg, BW), and the examples 1 to 7 groups (200 mg/kg, BW). Each group of mice is fed with SPF-grade growth and reproduction feed, free diet and drinking water, and each experimental group is subjected to gastric lavage once a day, the gastric lavage amount is 0.1mL/10g, the negative control group is subjected to gastric lavage with equal volume of physiological saline, and different test objects are subjected to continuous gastric lavage for 30 days. And the final administration is carried out for 15 minutes, the pentobarbital sodium is injected into the abdominal cavity of each group of animals, the injection quantity is 0.2mL/20g, the disappearance of the eversion and the reflection is taken as an index, whether the sample can prolong the sleeping time of the pentobarbital sodium is observed, and the difference of the sleeping prolonging time of each group is compared.
4. Experimental results
The experimental results are shown in Table 1. As can be seen from Table 1, the β -nicotinamide mononucleotide and the nervonic acid were used alone, which can shorten the sleep latency and prolong the sleep duration to some extent. The diazepam positive control group, example 2, example 3 and example 4 all shortened the mice' sleep latency and prolonged sleep duration with very significant differences compared to the blank control group. Of these, the composition of example 3 works best.
TABLE 1 Effect of different compositions on sodium pentobarbital-induced sleep time in mice
Group of Animal number (only) Sleep latency (min) Sleep time (min)
Negative control group 12 5.51±0.84 50±6.32
Positive control group 12 2.86±0.59** 84.75±7.28**
Beta-nicotinamide mononucleotide 12 4.07±0.73* 61.84±5.12*
Nervonic acid 12 3.83±0.65* 64.35±6.41*
Example 1 12 5.02±0.57 60.26±7.30
Example 2 12 3.76±0.49** 75.47±7.81**
Example 3 12 3.01±0.43** 83.64±6.35**
Example 4 12 3.89±0.58** 76.51±5.83**
Example 5 12 4.25±0.61* 71.39±8.12*
Example 6 12 4.53±0.75* 68.17±5.38*
Example 7 12 4.83±0.59 63.51±4.79
P <0.05, < P <0.01 compared to the negative control group.
Test example 2 evaluation of sleep improvement efficacy of compositions
1. Experimental materials
The composition prepared in example 3 of the present invention.
2. Experimental animal
144 healthy SPF-class female BALB/c mice, 6-8 weeks old, and 18-22 g in weight, provided by Sichuan university laboratory animal center, laboratory animal production license number SYXK (Sichuan) 2018-185, eligibility number: 00116042.
3. experimental method
(1) Grouping and treating animals: the mice are randomly divided into three large groups, one group of 48 mice is randomly divided into 4 dose groups, 12 mice in each group are subjected to a direct sleep experiment firstly, and then a sodium pentobarbital sleep time experiment is carried out the next day; two groups of 48 mice, randomly divided into 4 dose groups of 12 mice each, were subjected to pentobarbital sodium subthreshold dose hypnotic experiments; three groups of 48 mice, randomized into 4 dose groups of 12 each, were subjected to barbituric sodium sleep latency experiments.
(2) Direct sleep experiment: after administration by gastric lavage for 30 days, each group of mice was observed for sleep. Sleep is indicated by the disappearance of the eversion and the reflection. If the patient cannot turn over for more than 60 seconds, the patient considers that the turning over and the reflection disappear and goes to sleep. The recovery of the eversion and the reflection is the arousal of the animal. The period from the disappearance of the regular reflection to the restoration of the regular reflection is the sleep time of the animals, and the number of the animals falling asleep and the sleep time of each group are recorded.
(3) Prolonged pentobarbital sodium sleep time experiment: after the administration of the medicine for 30 days and 15 minutes after the last gastric lavage, 36mg/kg BW pentobarbital sodium is injected into the abdominal cavity of each group of animals, the injection amount is 0.2mL/20g, the disappearance of the regular reflection is taken as an index, and whether the tested sample can prolong the sleeping time of the pentobarbital sodium is observed.
(4) Pentobarbital sodium subthreshold dose hypnotic experiment: after the administration of the medicine for 30 days and 15 minutes after the last gastric lavage, the animals of each group are intraperitoneally injected with 30mg/kg BW pentobarbital sodium with the injection amount of 0.2mL/20g, the number of the animals falling asleep (the number of the animals with the regular reflection disappeared for more than 1 minute) is recorded within 30 minutes by taking the mice with the regular reflection disappeared for more than 1s as the standard of falling asleep. The experiment is preferably carried out in a quiet environment at 24-25 ℃.
(5) Barbital sodium sleep latency experiment: after the administration of the medicine for 30 days and 15 minutes after the last gastric lavage, the animals of each group are intraperitoneally injected with 260mg/kg BW barbital sodium and the injection amount is 0.2mL/20g, the disappearance of the regular reflection is taken as an index, and the influence of the sample on the sleeping latency of the barbital sodium is observed.
(6) And (3) statistical treatment: the SPSS 22.0 software is used for carrying out data processing on the original data of each experiment, and analysis of variance is used for carrying out significance test.
4. Experimental results
In the experimental process, animals drink water and ingest normally, and the appearance is not abnormal.
(1) Effect of the composition on mouse body weight
Mice were weighed before and one month after administration of different doses of the example 3 composition by gavage and were subjected to statistical analysis, and the results are shown in table 2. As can be seen from Table 2, the initial and final weights of the mice in each group were not statistically significant from group to group (P > 0.05).
Table 2 effect of composition on mouse body weight
Figure BDA0003391467880000061
(2) Effect of the composition on direct sleep in mice
Mice were given different doses of the example 3 composition by gavage for 30 days, and after the last administration, each group of mice had a sleep onset as shown in Table 3. As can be seen from Table 3, the compositions of example 3 had no effect on the direct sleep of mice in groups 100mg/kg/d, 200mg/kg/d, 300mg/kg/d and 0 mg/kg/d.
Table 3 effects of compositions on direct sleep in mice
Dosage (mg/kg/d) Animal number (only) Number of sleep occurrences (only)
0 12 0
100 12 0
200 12 0
300 12 0
(3) Effect of compositions on sodium pentobarbital-induced sleep time in mice
Mice were observed for sleep time by intraperitoneal injection of pentobarbital sodium after 30 days of different doses of the example 3 composition administered by gavage. As can be seen from the results in Table 4, the mice administered to each group had a sleep time longer than that of the 0mg/kg/d group, and had very significant differences at doses greater than 200 mg/kg/d.
Effect of table 4 composition on sodium pentobarbital on sleep time in mice
Figure BDA0003391467880000062
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Figure BDA0003391467880000071
P <0.05, P <0.01 compared to the negative control group.
(4) Effect of composition on sub-threshold dose hypnotic effect of pentobarbital sodium
Mice were given different doses of the example 3 composition by gavage for 30 days, and each group of mice was observed for sleep occurrence within 30min by intraperitoneal injection of pentobarbital sodium. As can be seen from the results in Table 5, the sleep occurrence rate of animals in the 100mg/kg/d, 200mg/kg/d and 300mg/kg/d groups was significantly increased as compared with the 0mg/kg/d group, and the sleep occurrence rate of animals in each group was significantly increased as compared with the 0mg/kg/d group, wherein the composition doses of the 200mg/kg/d and 300mg/kg/d groups were statistically significant.
Effect of table 5 compositions on the incidence of sleep in mice induced by sub-threshold doses of sodium pentobarbital
Dosage (mg/kg/d) Animal number (only) Number of animals falling asleep (Only) Incidence of sleep (%)
0 12 1 8.33
100 12 3 25.00
200 12 6 50.00*
300 12 9 75.00*
P <0.05 compared to negative control group.
(5) Effect of the composition on sodium barbiturate sleep latency
Mice were given different doses of the example 3 composition by gavage for 30 days, and were observed for sleep latency by intraperitoneal injection of barbital sodium. As can be seen from table 6, the intervention of different doses of administration significantly shortened the barbituric sodium sleep latency of mice compared to the blank control group.
Effects of Table 6 compositions on barbituric sodium sleep latency
Dosage (mg/kg/d) Animal number (only) Sleep latency (min)
0 12 31.54±5.61
100 12 25.38±6.19
200 12 18.63±5.73*
300 12 16.42±4.52*
P <0.05 compared to negative control group
According to the result judgment of the "health food function evaluation method (2020 edition)" which is useful for improving sleep function, the β -nicotinamide mononucleotide and nervonic acid composition of the present invention has an effect of useful for improving sleep function.

Claims (7)

1. A composition comprising β -nicotinamide mononucleotide and a nervonic acid, characterized in that the active ingredient consists of the following weight percentages: 20-70% of beta-nicotinamide mononucleotide and the balance of nervonic acid.
2. The composition comprising β -nicotinamide mononucleotide and nervonic acid according to claim 1, characterized in that the active ingredients thereof consist of the following weight percentages: 30-50% of beta-nicotinamide mononucleotide and the balance of nervonic acid.
3. The composition comprising β -nicotinamide mononucleotide and nervonic acid according to claim 1, characterized in that the active ingredients thereof consist of the following weight percentages: 30-40% of beta-nicotinamide mononucleotide and the balance of nervonic acid.
4. The composition comprising β -nicotinamide mononucleotide and nervonic acid according to claim 1, characterized in that the active ingredients thereof consist of the following weight percentages: beta-nicotinamide mononucleotide 40% and the rest is nervonic acid.
5. The composition comprising β -nicotinamide mononucleotide and a nervonic acid of claim 1, wherein: the composition also comprises auxiliary materials.
6. The composition comprising β -nicotinamide mononucleotide and a nervonic acid of claim 5, wherein: the composition is in the form of granule, tablet, capsule, pill, paste, beverage, solid beverage or biscuit.
7. Use of a composition comprising a β -nicotinamide mononucleotide and a nervonic acid according to any one of claims 1-6 for the preparation of a food, a health product or a pharmaceutical product for improving sleep.
CN202111470104.5A 2021-12-03 2021-12-03 Composition containing beta-nicotinamide mononucleotide and nervonic acid and application thereof Pending CN116210907A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
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