WO2023216951A1 - 一种抗衰老的含有尿苷酸、腺苷酸和酵母肽的组合物及其应用 - Google Patents

一种抗衰老的含有尿苷酸、腺苷酸和酵母肽的组合物及其应用 Download PDF

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WO2023216951A1
WO2023216951A1 PCT/CN2023/091947 CN2023091947W WO2023216951A1 WO 2023216951 A1 WO2023216951 A1 WO 2023216951A1 CN 2023091947 W CN2023091947 W CN 2023091947W WO 2023216951 A1 WO2023216951 A1 WO 2023216951A1
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parts
acid
yeast peptide
adenylic
uridylic
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PCT/CN2023/091947
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English (en)
French (fr)
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李勇
徐美虹
陈玉松
曾峥
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陈玉松
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/01—Hydrolysed proteins; Derivatives thereof
    • A61K38/011—Hydrolysed proteins; Derivatives thereof from plants
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • 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
    • A61K31/7064—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 containing condensed or non-condensed pyrimidines
    • A61K31/7068—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 containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—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 containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • 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
    • A61K31/7064—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 containing condensed or non-condensed pyrimidines
    • A61K31/7076—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 containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • 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
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention belongs to the technical field of medicine and health care, and specifically relates to an anti-aging composition containing uridylic acid, adenylic acid and yeast peptide and its application.
  • Anti-aging products currently on the market use industrial ingredients with strong antioxidant properties in order to achieve good anti-aging effects and have quick results in a short time. However, 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.
  • Nucleotides are the basic building blocks of ribonucleic acid and deoxyribonucleic acid, and are the precursors of nucleic acid synthesis in the body. Nucleotides are distributed along with nucleic acids in the nuclei and cytoplasm of various organs, tissues, and cells in organisms, and as components of nucleic acids, they participate in basic life activities such as inheritance, development, and growth of organisms.
  • the object of the present invention is to provide an anti-aging composition containing uridylic acid, adenylic acid and yeast peptide and its application.
  • the present invention found that different nucleotides have different functions, and when combined with other functional ingredients (especially yeast peptides), they can effectively remove free radicals in the body, delay cell aging, and restore youthfulness. .
  • the present invention provides a new idea for the application of nucleotide nutritional products in improving human health and people's quality of life.
  • An anti-aging composition containing uridylic acid, adenylic acid and yeast peptide includes 5'-uridylic acid, 5'-adenylic acid, yeast peptide and functional active ingredients, the functional activity Ingredients include velvet antler extract, pyrroloquinoline quinone (PQQ), glutathione, curcumin, tea polyphenols, quercetin, resveratrol, alpha-lipoic acid, alpha-pentaronic acid, fisetin one or more than two of them.
  • the 5'-uridylic acid, 5'-adenylic acid, yeast peptide and functional ingredients in the composition include the following parts by weight: 0.3-1.2 parts of 5'-adenylic acid , 0.3-1.2 parts of 5'-uridylic acid, 0.05-1.5 parts of yeast peptide, and 0.88-7.35 parts of functional active ingredients.
  • the functionally active ingredients include the following components by weight: 1-2 parts by weight of velvet antler extract, 0.01-0.05 parts by pyrroloquinoline quinone, 0.25-1 part by glutathione, and 0.12-0.12 parts by curcumin. 0.6 parts, tea polyphenols 0.5-1 parts, quercetin 0.5-1.25 parts, resveratrol 0.02-0.1 parts, ⁇ -lipoic acid 0.01-0.1 parts, ⁇ -pentanoic acid 0.3-1 parts, Fisser One or more than two kinds of ketones 0.05-0.25 parts.
  • the composition includes the following components by weight: 0.6 parts of 5'-adenylic acid, 0.6 parts of 5'-uridylic acid, 0.25 parts of yeast peptide, 2 parts of velvet antler extract, 0.02 parts of pyrroloquinoline quinone, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, 0.5 parts of quercetin, and 0.051 parts of resveratrol; or the composition includes the following weight parts: Points: 0.6 parts of 5'-adenylic acid, 0.6 parts of 5'-uridylic acid, 0.25 parts of yeast peptide, 2 parts of velvet antler extract, 0.05 parts of ⁇ -lipoic acid, 0.3 parts of ⁇ -pentanoic acid, pyrroloquinoline Quinone 0.02 part, curcumin 0.19 part, fisetin 0.1 part, glutathione 0.25 part, resveratrol 0.051 part.
  • the composition includes the following components by weight: 0.3 parts of 5'-uridylic acid, 0.3 parts of 5'-adenylic acid, 0.17 parts of yeast peptide, and 0.01 parts of pyrroloquinoline quinone , 0.25 parts of glutathione, 0.12 parts of curcumin, 0.5 parts of tea polyphenols; or 0.6 parts of 5'-uridylic acid, 0.6 parts of 5'-adenylic acid, 0.25 parts of yeast peptide, 0.02 parts of pyrroloquinoline quinone, Glutathione 0.25 parts, curcumin 0.19 parts, tea polyphenols 0.5 parts, quercetin 0.5 parts, resveratrol 0.051 parts; or 5'-uridylic acid 0.3 parts, 5'-adenylic acid 0.3 parts, 0.17 parts of yeast peptide, 0.05 parts of fisetin, 0.01 parts of pyrroloquinoline quinone, 0.25 parts of glutathione, 0.12 parts of
  • the velvet antler extract is derived from fresh velvet antler.
  • the fresh velvet antler used in the present invention is preferably the young unossified and densely covered with velvet antlers of sika deer (Cervus nippon Temminck) or red deer (Cervus elaphus Linnaeus).
  • the extraction method of the velvet antler extract used in the present invention is not limited to the conventional lysis method, organic solvent extraction, enzymatic hydrolysis, ultrasonic fragmentation, CO 2 supercritical extraction, high-voltage pulsed electric field (PEF) and other technologies conventional in the field.
  • the main components of the velvet antler extract used in the present invention are polypeptides, proteins and polysaccharides.
  • the effect of the present invention can be achieved if the velvet antler extract contains polypeptides of 100-5000 Da with a content of more than 40 wt.%, collagen and keratin content of more than 10 wt.%, and polysaccharides with a content of more than 30 wt.%.
  • the velvet antler extract contains polypeptides of 100-5000 Da with a content of more than 40 wt.%, collagen and keratin content of more than 10 wt.%, and polysaccharides with a content of more than 30 wt.%.
  • the yeast peptide used in the present invention is a fully nutritional yeast fermentation product. Its main components are short peptides of 500-2000 Da or less (peptides composed of 5-20 amino acids) and various amino acids. It also contains polysaccharides, multiple vitamins, minerals and Dietary fiber supplements various nutrients that the aging body lacks.
  • the yeast peptide contains more than 40wt.% of short peptides of 500-2000Da or less (peptides composed of 5-20 amino acids), and contains amino acids that meet the requirements of essential amino acids/total amino acids of more than 40wt.%, and branched chain amino acids. When the amino acid/total amino acid ratio is greater than 15wt.%, the effect of the present invention can be achieved.
  • the yeast used in the present invention is preferably Saccharomyces cerevisiae, and the fermentation substrate is preferably molasses, including sugar cane molasses, beet molasses, etc., in which phosphoric acid, zinc sulfate, ammonium sulfate, magnesium sulfate, etc. are added as fermentation nutrients.
  • the finished product state of the composition includes powder, granule, tablet, pill, oral liquid, and capsule.
  • the present invention also provides the use of the above-mentioned composition containing uridylic acid, adenylic acid and yeast peptide in the preparation of anti-aging drugs, health products or nutritious foods.
  • the medicines, health products or nutritional foods have the functions of scavenging free radicals in the body, anti-oxidation, good protection and repair of damaged cells, delaying the aging of the body, and restoring youthfulness.
  • the invention provides compositions and applications containing 5'-uridylic acid, 5'-adenylic acid, yeast peptides and other functional active ingredients.
  • the functional active ingredients include velvet antler extract, pyrroloquinoline quinone (PQQ), One or more of glutathione, curcumin, tea polyphenols, quercetin, resveratrol, alpha-lipoic acid, alpha-pentarondioic acid, and fisetin.
  • PQQ pyrroloquinoline quinone
  • 5’-uridylic acid and 5’-adenylic acid can increase the survival rate of gastrointestinal probiotics, thereby improving the intestinal environment, promoting the decomposition of macromolecules, and accelerating the absorption and transportation of various active ingredients. Therefore, it is speculated and verified by experimental results that the combination of nucleotides, yeast peptides and other active ingredients can enhance the anti-aging and anti-aging effects of the composition.
  • Figure 1 shows the effect of the composition containing uridylic acid, adenylic acid and yeast peptide according to the present invention on the glutathione peroxidase (GSH-PX) content in the serum of D-galactose mice.
  • # indicates that the difference is statistically significant (P ⁇ 0.05) compared with the model group; * indicates that the difference is statistically significant (P ⁇ 0.05) compared with the blank group.
  • Figure 2 shows the effect of the composition containing uridylic acid, adenylic acid and yeast peptide according to the present invention on the superoxide dismutase (SOD) content in the serum of D-galactose mice.
  • # indicates that the difference is statistically significant (P ⁇ 0.05) compared with the model group; * indicates that the difference is statistically significant (P ⁇ 0.05) compared with the blank group.
  • Figure 3 shows the effect of the composition containing uridylic acid, adenylic acid and yeast peptide according to the present invention on the content of malondialdehyde (MDA) in the serum of D-galactose mice.
  • MDA malondialdehyde
  • Figure 4 shows the effect of the composition containing uridylic acid, adenylic acid and yeast peptide according to the present invention on the lifespan of aging mice.
  • weight ratio 0.6 parts of 5'-uridylic acid, 0.6 parts of 5'-adenylic acid, 0.25 parts of yeast peptide, 2 parts of velvet antler extract, 0.02 parts of PQQ, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, 0.5 parts of quercetin, and 0.051 parts of resveratrol were weighed in a clean area and mixed evenly with a mixer to obtain a powder. Finished products are sampled and inspected for various indicators in accordance with the quality standards. After passing the inspection, they are stored for future use.
  • the weight ratio it is 0.6 parts of 5'-uridylic acid, 0.6 parts of 5'-adenylic acid, 0.25 parts of yeast peptide, 2 parts of velvet antler extract, 0.05 parts of ⁇ -lipoic acid, 0.3 parts of ⁇ -pentalonedioic acid, 0.02 parts of pyrroloquinoline quinone, 0.19 parts of curcumin, 0.1 parts of fisetin, 0.25 parts of glutathione, and 0.051 parts of resveratrol were weighed in a clean area and mixed evenly with a mixer to obtain a powder. Finished products are sampled and inspected for various indicators in accordance with the quality standards. After passing the inspection, they are stored for future use.
  • weight ratio 0.3 parts of 5'-uridylic acid, 0.3 parts of 5'-adenylic acid, 0.17 parts of yeast peptide, 0.01 parts of PQQ, 0.25 parts of glutathione, 0.12 parts of curcumin, and 0.5 parts of tea polyphenols.
  • weight ratio 0.6 parts of 5'-uridylic acid, 0.6 parts of 5'-adenylic acid, 0.25 parts of yeast peptide, 0.02 parts of PQQ, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, Weigh 0.5 parts of quercetin and 0.051 parts of resveratrol in a clean area and mix them evenly with a mixer to obtain a powder. Finished products are sampled and inspected for various indicators in accordance with the quality standards. After passing the inspection, they are stored for future use.
  • weight ratio 0.3 parts of 5'-uridylic acid, 0.3 parts of 5'-adenylic acid, 0.17 parts of yeast peptide, 0.05 parts of fisetin, 0.01 parts of PQQ, 0.25 parts of glutathione, 0.12 parts of curcumin, 0.5 parts of tea polyphenols
  • 0.3 parts of 5'-uridylic acid, 0.3 parts of 5'-adenylic acid, 0.17 parts of yeast peptide, 0.05 parts of fisetin, 0.01 parts of PQQ, 0.25 parts of glutathione, 0.12 parts of curcumin, 0.5 parts of tea polyphenols Weigh the raw materials in a clean area and mix them evenly with a mixer to obtain a powder. Finished products are sampled and inspected for various indicators in accordance with the quality standards. After passing the inspection, they are stored for future use.
  • the weight ratio is 0.6 parts of 5'-adenylic acid, 0.6 parts of 5'-uridylic acid, 0.25 parts of yeast peptide, 0.05 parts of ⁇ -lipoic acid, 0.3 parts of ⁇ -pentarondioic acid, and 0.02 parts of pyrroloquinoline quinone. , 0.19 parts of curcumin, 0.1 parts of fisetin, 0.25 parts of glutathione, and 0.051 parts of resveratrol. Weigh the raw materials in a clean area and mix them evenly with a mixer to obtain a powder. Finished products are sampled and inspected for various indicators in accordance with the quality standards. After passing the inspection, they are stored for future use.
  • Example 7 Antioxidant properties of compositions containing uridylic acid, adenylic acid and yeast peptides
  • Example 1 The powder prepared in Example 1 was prepared and weighed and then dissolved in a mixed solution of deionized water and ethanol (volume ratio was 1:1) to prepare a mother solution with a concentration of 1 mg/mL, and the DPPH radical scavenging rate was measured. and determination of OH - radical scavenging rates.
  • the DPPH free radical scavenging rate formula is as follows:
  • a blank is the absorbance of 150 ⁇ L deionized water ethanol solution and 150 ⁇ L DPPH solution
  • a sample is the absorbance of 150 ⁇ L sample and 150 ⁇ L DPPH solution
  • IC 50 is the concentration of the sample when the DPPH free radical scavenging rate reaches 50%.
  • a blank is the absorbance of the sample using DMSO instead of the system
  • a sample is the absorbance of the 50 ⁇ L sample.
  • IC 50 is the concentration of the sample at which the OH - radical scavenging rate reaches 50%.
  • Control group 1 single component 5’-uridylic acid.
  • Control group 2 single component 5’-adenylate.
  • Control group 3 single-component yeast peptide.
  • Control group 4 a compound composition of 0.6 parts of 5’-uridylic acid and 0.6 parts of 5’-adenylic acid.
  • Control group 5 a compound composition of 0.6 parts of 5’-uridylic acid, 0.6 parts of 5’-adenylic acid, and 0.25 parts of yeast peptide.
  • Control group 6 a compound composition of 0.6 parts of 5'-guanylic acid, 0.6 parts of 5'-cytidylic acid, and 0.25 parts of yeast peptide.
  • Control group 7 0.25 parts of yeast peptide, 2 parts of velvet antler extract, 0.02 parts of PQQ, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, 0.5 parts of quercetin, and 0.051 parts of resveratrol.
  • Control group 8 0.25 parts of yeast peptide, 0.02 parts of PQQ, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, 0.5 parts of quercetin, and 0.051 parts of resveratrol.
  • compositions containing uridylic acid, adenylic acid and yeast peptide of Examples 1-6 all have higher antioxidant properties and show stronger elimination of DPPH free radicals. and OH - free radicals.
  • the antioxidant properties show a significantly enhanced effect.
  • the compositions of Examples 1-6 can more effectively remove free radicals from the body. base.
  • composition prepared by compounding uridylic acid, adenylic acid, yeast peptide and functional active ingredients according to the present invention is only yeast peptide compared with single-component uridylic acid, single-component adenylic acid and single-component yeast peptide.
  • nucleotide compound two kinds of nucleotide compound (5'-uridylic acid and 5'-adenylic acid compounded in a weight ratio of 1:1), two kinds of nucleotide compound yeast peptide (5'- Uridylic acid: 5'-adenylic acid: yeast peptide in a weight ratio of 0.6:0.6:0.25) or a mixture of 5'-guanylic acid, 5'-cytidylic acid and yeast peptide all have significant clearance
  • the ability of free radicals, scavenging DPPH free radicals and scavenging OH - free radicals has been significantly improved. At the same time, it can enhance the activity of antioxidant enzymes in the organism and achieve the purpose of delaying aging.
  • Uridylic acid and adenylic acid work synergistically with yeast peptides to enhance the ability to scavenge free radicals. After compounding functional active ingredients, the effect is further improved.
  • Example 8 Anti-aging properties of a composition containing uridylic acid, adenylic acid and yeast peptide in vitro
  • H 2 O 2 was used to create the model, and the intracellular ROS levels of the compositions of Examples 1-6 were evaluated.
  • Control group 1 single component 5’-uridylic acid.
  • Control group 2 single component 5’-adenylate.
  • Control group 3 single-component yeast peptide.
  • Control group 4: A compound compound of 0.6 parts of 5’-uridylic acid and 0.6 parts of 5’-adenylic acid.
  • Control group 5 a compound composition of 0.6 parts of 5’-uridylic acid, 0.6 parts of 5’-adenylic acid, and 0.25 parts of yeast peptide.
  • Control group 6 a compound composition of 0.6 parts of 5'-guanylic acid, 0.6 parts of 5'-cytidylic acid, and 0.25 parts of yeast peptide.
  • Control group 7 0.25 parts of yeast peptide, 2 parts of velvet antler extract, 0.02 parts of PQQ, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, 0.5 parts of quercetin, and 0.051 parts of resveratrol.
  • Control group 8 0.25 parts of yeast peptide, 0.02 parts of PQQ, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, 0.5 parts of quercetin, and 0.051 parts of resveratrol.
  • H 2 O 2 produces a large amount of ROS after acting on cells, attacking cell membranes, proteins and nucleic acids, causing cell damage.
  • Cells in the logarithmic growth phase were digested into a single cell suspension, adjusted to a cell concentration of 10 5 cells/mL, and seeded in a 96-well cell culture plate, with 100 ⁇ L per well and 6 parallel wells in each group. 24 hours after inoculation, the cells grew adherently. The supernatant was discarded, a H 2 O 2 medium with a final concentration of 200 ⁇ mol/L was added and cultured for 4 hours, and then replaced with the compositions of Examples 1-6 with a final concentration of 50 ⁇ g/mL. The culture medium was continued to be cultured for 24 hours.
  • the experiment also set up a blank control without adding H 2 O 2 and a model group with only H 2 O 2 added.
  • Use a fluorescent microplate reader to measure the fluorescence of each well under the conditions of excitation wavelength 485 nm and emission wavelength 525 nm. Intensity, calculate the reactive oxygen species content of cells.
  • the experimental data are expressed as mean ⁇ standard deviation, and the experimental results are shown in Table 2.
  • compositions of Examples 1-6 can significantly reduce the reactive oxygen species in the model cells. Has good protection and repair effects.
  • composition prepared by compounding uridylic acid, adenylic acid, yeast peptide and functional active ingredients according to the present invention is only yeast peptide compared with single-component uridylic acid, single-component adenylic acid and single-component yeast peptide.
  • nucleotide compound two kinds of nucleotide compound (5'-uridylic acid and 5'-adenylic acid compounded in a weight ratio of 1:1), two kinds of nucleotide compound yeast peptide (5'- Uridylic acid: 5'-adenylic acid: yeast peptide is compounded at a weight ratio of 0.6:0.6:0.25) or a mixture of 5'-guanylic acid, 5'-cytidylic acid and yeast peptide has a significant reduction
  • the ability of H 2 O 2 to damage the intracellular reactive oxygen content helps to repair aging oxidatively damaged cells, and the ability to reduce the intracellular reactive oxygen content is significantly improved.
  • Uridylic acid and adenylic acid have a synergistic effect with yeast peptide, enhancing the ability to reduce intracellular reactive oxygen species. After compounding functional active ingredients, the effect is further improved.
  • Example 9 Effect of a composition containing uridylic acid, adenylic acid and yeast peptide on D-galactose-induced mice
  • mice 5-week-old BALB/c mice were raised for one week, and 20 of them were intraperitoneally injected with 50 mg/kg D-galactose for 30 days. After 30 days, 10 mice were divided into groups.
  • compositions of Examples 1-6 were orally administered for 28 days, and D-galactose was injected intraperitoneally at the same time.
  • Control group 1 The same volume of 5'-uridylic acid as the composition was orally administered for 28 days, and D-galactose was injected intraperitoneally at the same time.
  • Control group 2 The same volume of 5'-adenosine as the composition was orally administered for 28 days, and D-galactose was injected intraperitoneally at the same time.
  • Control group 3 The same volume of yeast peptide as the composition was orally administered for 28 days, and D-galactose was injected intraperitoneally at the same time.
  • Control group 4 A combination of 0.6 parts of 5'-uridylic acid and 0.6 parts of 5'-adenylic acid of the same volume as the composition was administered orally. The animals were kept for 28 days, and D-galactose was injected intraperitoneally at the same time.
  • Control group 5 A compound composed of 0.6 parts of 5'-uridylic acid, 0.6 parts of 5'-adenylic acid, and 0.25 parts of yeast peptide with the same volume as the composition was orally administered for 28 days, and D-half was injected intraperitoneally at the same time. lactose.
  • Control group 6 A compound containing 0.6 parts of 5'-guanylic acid, 0.6 parts of 5'-cytidylic acid, and 0.25 parts of yeast peptide in the same volume as the composition was orally administered for 28 days, and D-half was injected intraperitoneally at the same time. lactose.
  • Control group 7 Oral administration of 0.25 parts of yeast peptide, 2 parts of velvet antler extract, 0.02 parts of PQQ, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, and 0.5 parts of quercetin in the same volume as the composition. , a compound compound of 0.051 parts of resveratrol for 28 days, and D-galactose was injected intraperitoneally at the same time.
  • Control group 8 Oral administration of 0.25 parts of yeast peptide, 0.02 parts of PQQ, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, 0.5 parts of quercetin, and 0.051 parts of resveratrol in the same volume as the composition.
  • the compounded composition was administered for 28 days, and D-galactose was injected intraperitoneally at the same time.
  • Model group intragastric administration of the same volume of PBS buffer as the composition.
  • Blank group intraperitoneally injected the same dose of physiological saline as D-galactose, 30 days later, intragastrically administered the same volume of PBS buffer as the composition, and continued intraperitoneal injection for a total of 28 days.
  • Example 10 Delaying effect of the composition of uridylic acid, adenylic acid and yeast peptide on aging in naturally aging mice
  • mice Eight-week-old BALB/c mice were randomly divided into two groups, with 10 mice in each group.
  • the compositions of Examples 1-6 were administered by gavage until the mice died of natural aging.
  • Blank group The same amount of physiological saline as mentioned above was administered by gavage until the mice aged and died naturally.
  • Control group 1 The same volume of 5'-uridylic acid as the composition was orally administered until the mice died of natural aging.
  • Control group 2 The same volume of 5'-adenylic acid as the composition was administered by gavage until the mice aged and died naturally.
  • Control group 3 The same volume of yeast peptide as the composition was orally administered until the mice aged and died naturally.
  • Control group 4 A compound composed of 0.6 parts of 5'-uridylic acid and 0.6 parts of 5'-adenylic acid in the same volume as the composition was orally administered until the mice died of natural aging.
  • Control group 5 A compound composed of 0.6 parts of 5'-uridylic acid, 0.6 parts of 5'-adenylic acid, and 0.25 parts of yeast peptide with the same volume as the composition was orally administered until the mice aged and died naturally.
  • Control group 6 A compound composed of 0.6 parts of 5'-guanylic acid, 0.6 parts of 5'-cytidylic acid, and 0.25 parts of yeast peptide in the same volume as the composition was orally administered until the mice aged and died naturally.
  • Control group 7 Oral administration of 0.25 parts of yeast peptide, 2 parts of velvet antler extract, 0.02 parts of PQQ, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, and 0.5 parts of quercetin in the same volume as the composition. ,white The compound containing 0.051 parts of veratrol was used until the mice aged and died naturally.
  • Control group 8 Oral administration of 0.25 parts of yeast peptide, 0.02 parts of PQQ, 0.25 parts of glutathione, 0.19 parts of curcumin, 0.5 parts of tea polyphenols, 0.5 parts of quercetin, and 0.051 parts of resveratrol in the same volume as the composition. of the compounded composition until the mouse senile and died naturally.
  • mice The growth and lifespan of mice in each group were calculated separately. The results are shown in Figure 4.
  • the composition containing uridylic acid, adenylic acid and yeast peptide according to the present invention can effectively delay the natural aging of mice.

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Abstract

一种抗衰老的含有尿苷酸、腺苷酸和酵母肽的组合物及其应用，属于医药保健技术领域。所述组合物由5'-尿苷酸、5'-腺苷酸、酵母肽和功能活性成分按照一定比例调配制成，所述功能活性成分为鹿茸提取物、吡咯喹啉醌（PQQ）、谷胱甘肽、姜黄素、茶多酚、槲皮素、白藜芦醇、α-硫辛酸、α-戊酮二酸、非瑟酮中的一种或者几种。所述含有尿苷酸、腺苷酸和酵母肽的组合物具有延缓机体衰老、恢复年轻态等作用，使用后可起到延缓、改善、防止衰老的功效。

Description

一种抗衰老的含有尿苷酸、腺苷酸和酵母肽的组合物及其应用 技术领域
本发明属于医药保健技术领域，具体涉及一种抗衰老的含有尿苷酸、腺苷酸和酵母肽的组合物及其应用。
背景技术
衰老作为生命历程里必经的阶段一直伴随着人类文明的发展，进入21世纪，人们对于衰老进行了更加深度的研究，人们对于衰老的认知也逐渐变化，目前凡是有利于人体健康的，提高生活质量的，都可定义为延缓衰老。延缓衰老的主要方式为非药物与药物两个方面，其中非药物的方法为坚持科学的生活规律，保持良好的生活习惯。而药物的方法分类就比较多，其中大多数是服用保健类药品或食品，其作用效果也是最显著的。
目前市面上的抗衰老产品为了达到很好的抗衰老效果使用了抗氧化性强的工业成分、短时见效快，但是长时间使用对人体危害极大；有的抗衰产品添加维生素类抗氧化剂，但是这类产品稳定性差。
核苷酸是核糖核酸及脱氧核糖核酸的基本组成单位，是体内合成核酸的前身物。核苷酸随着核酸分布于生物体内各器官、组织、细胞的核及胞质中，并作为核酸的组成成分参与生物的遗传、发育、生长等基本生命活动。
发明内容
本发明的目的在于提供一种抗衰老的含有尿苷酸、腺苷酸和酵母肽的组合物及其应用。本发明经过长期研究，本发明经过长期研究发现，不同的核苷酸有不同的功能，搭配添加其他功能性成分(尤其是酵母肽)后可以高效清除体内自由基，延缓细胞老化，恢复年轻态。本发明为核苷酸类营养品在提高人体健康水平、人们生活质量的应用方面提供了一种新思路。
本发明为实现上述目的，通过以下技术方案实现：
一种抗衰老的含有尿苷酸、腺苷酸和酵母肽的组合物，所述组合物包括5’-尿苷酸、5’-腺苷酸、酵母肽和功能活性成分，所述功能活性成分包括鹿茸提取物、吡咯喹啉醌(PQQ)、谷胱甘肽、姜黄素、茶多酚、槲皮素、白藜芦醇、α-硫辛酸、α-戊酮二酸、非瑟酮中的一种或者两种以上。
进一步地，上述技术方案中，所述组合物中5’-尿苷酸、5’-腺苷酸、酵母肽和功能性成分包括如下重量份数组分：5’-腺苷酸0.3-1.2份、5’-尿苷酸0.3-1.2份、酵母肽0.05-1.5份、功能活性成分0.88-7.35份。
进一步地，上述技术方案中，所述功能活性成分包括如下重量份数组分：鹿茸提取物1-2份、吡咯喹啉醌0.01-0.05份、谷胱甘肽0.25-1份、姜黄素0.12-0.6份、茶多酚0.5-1份、槲皮素0.5-1.25份、白藜芦醇0.02-0.1份、α-硫辛酸0.01-0.1份、α-戊酮二酸0.3-1份、非瑟酮0.05-0.25份中的一种或者两种以上。
进一步地，上述技术方案中，所述组合物包括如下重量份数的组分：5’-腺苷酸0.6份、5’-尿苷酸0.6份、酵母肽0.25份、鹿茸提取物2份、吡咯喹啉醌0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份；或者所述组合物包括如下重量份数的组分：5’-腺苷酸0.6份、5’-尿苷酸0.6份、酵母肽0.25份、鹿茸提取物2份、α-硫辛酸0.05份、α-戊酮二酸0.3份、吡咯喹啉醌0.02份、姜黄素0.19份、非瑟酮0.1份、谷胱甘肽0.25份、白藜芦醇0.051份。
进一步地，上述技术方案中，所述组合物包括如下重量份数的组分：5’-尿苷酸0.3份、5’-腺苷酸0.3份、酵母肽0.17份、吡咯喹啉醌0.01份、谷胱甘肽0.25份、姜黄素0.12份、茶多酚0.5份；或者5’-尿苷酸0.6份、5’-腺苷酸0.6份、酵母肽0.25份、吡咯喹啉醌0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份；或5’-尿苷酸0.3份、5’-腺苷酸0.3份、酵母肽0.17份、非瑟酮0.05份、吡咯喹啉醌0.01份、谷胱甘肽0.25份、姜黄素0.12份、茶多酚0.5份；或5’-腺苷酸0.6份、5’-尿苷酸0.6份、酵母肽0.25份、α-硫辛酸0.05份、α-戊酮二酸0.3份、吡咯喹啉醌0.02份、姜黄素0.19份、非瑟酮0.1份、谷胱甘肽0.25份、白藜芦醇0.051份。
进一步地，上述技术方案中，所述鹿茸提取物来源于新鲜鹿茸。本发明所使用的新鲜鹿茸优选为梅花鹿(Cervus nippon Temminck)或马鹿(Cervus elaphus Linnaeus)的雄鹿未骨化密生茸毛的幼角。本发明使用的鹿茸提取物的提取方法不限于本领域常规的裂解法、有机溶剂萃取、酶解法、超声波破碎、CO2超临界萃取和高压脉冲电场(PEF)等技术。本发明使用的鹿茸提取物的主要成份为多肽、蛋白质和多糖。本发明中，所述鹿茸提取物含有多肽100-5000Da含量40wt.％以上、胶原蛋白和角蛋白含量大于10wt.％、多糖含量30wt.％以上，就可以达到本发明的效果。对于其它成分不做具体限定，只要使用本领域常规方法进行提取的提取物即可。
本发明所使用的酵母肽是一种全营养酵母发酵产物，主要成分为500-2000Da以下短肽(5-20个氨基酸组成的肽)和各种氨基酸，还含有多糖、多种维生素矿物质以及膳食纤维补充衰老机体所缺各类营养成分。在本发明中，酵母肽含有500-2000Da以下短肽(5-20个氨基酸组成的肽)40wt.％以上，含有的氨基酸满足必需氨基酸/总氨基酸大于40wt.％、支链氨 基酸/总氨基酸大于15wt.％，即可到达本发明效果。对于多糖、多种维生素矿物质以及膳食纤维等其它营养成分不做具体限定，只要使用本领域常规的方法进行全营养酵母发酵的发酵产物即可。本发明中使用的酵母优选为酿酒酵母，发酵基质优选为糖蜜，包括甘蔗糖蜜、甜菜糖蜜等，其中添加磷酸、硫酸锌、硫酸铵、硫酸镁等作为发酵营养物质。
进一步地，上述技术方案中，所述组合物的成品状态包括粉剂、颗粒剂、片剂、丸剂、口服液、胶囊。
本发明还提供了上述含有尿苷酸、腺苷酸和酵母肽的组合物在制备抗衰老药品、保健品或营养食品中的应用。
进一步地，上述技术方案中，所述药品、保健品或营养食品具有清除体内自由基、抗氧化、对损伤细胞良好的保护和修复、延缓机体衰老、恢复年轻态的作用。
本发明相对于现有技术具有的有益效果如下：
本发明提供了包含5’-尿苷酸、5’-腺苷酸、酵母肽及其他功能活性成分的组合物及应用，所述功能活性成分包括鹿茸提取物、吡咯喹啉醌(PQQ)、谷胱甘肽、姜黄素、茶多酚、槲皮素、白藜芦醇、α-硫辛酸、α-戊酮二酸、非瑟酮中的一种或者两种以上。研究发现5’-尿苷酸、5’-腺苷酸可提升胃肠道益生菌存活率进而改善肠道环境，促进大分子物质分解，加速多种活性成分的的吸收与转运。因此，推测并经实验结果验证，核苷酸、酵母肽和其他活性成分配伍，可加强组合物延缓衰老和抗衰老的功效。
附图说明
图1为本发明所述含有尿苷酸、腺苷酸和酵母肽的组合物对D-半乳糖小鼠血清中谷胱甘肽过氧化物酶(GSH-PX)含量的影响。图中：#表示与模型组比较，差异有统计学意义(P＜0.05)；*表示与空白组比较，差异有统计学意义(P＜0.05)。
图2为本发明所述含有尿苷酸、腺苷酸和酵母肽的组合物对D-半乳糖小鼠血清中超氧化物歧化酶(SOD)含量的影响。图中：#表示与模型组比较，差异有统计学意义(P＜0.05)；*表示与空白组比较，差异有统计学意义(P＜0.05)。
图3为本发明所述含有尿苷酸、腺苷酸和酵母肽的组合物对D-半乳糖小鼠血清中丙二醛(MDA)含量的影响。图中：#表示与模型组比较，差异有统计学意义(P＜0.05)。
图4为本发明所述含有尿苷酸、腺苷酸和酵母肽的组合物对衰老小鼠寿命的影响。
具体实施方式
下面结合具体实施例对本发明的作进一步解释说明，这些实施例应被理解为仅是举例说明，而非以任何方式限制本发明的范围。下述实施例中，如无特殊说明，所使用的实验方法 均为常规方法，所用材料、试剂等均可从生物或化学公司购买。
实施例1
按照重量配比为5’-尿苷酸0.6份、5’-腺苷酸0.6份、酵母肽0.25份、鹿茸提取物2份、PQQ 0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份在洁净区称取原料，用混合机混合均匀，得到粉剂。成品按质量标准的规定取样进行各项指标的检验，检验合格后保存备用。
实施例2
按照重量配比为5’-尿苷酸0.6份、5’-腺苷酸0.6份、酵母肽0.25份、鹿茸提取物2份、α-硫辛酸0.05份、α-戊酮二酸0.3份、吡咯喹啉醌0.02份、姜黄素0.19份、非瑟酮0.1份、谷胱甘肽0.25份、白藜芦醇0.051份在洁净区称取原料，用混合机混合均匀，得到粉剂。成品按质量标准的规定取样进行各项指标的检验，检验合格后保存备用。
实施例3
按照重量配比为5’-尿苷酸0.3份、5’-腺苷酸0.3份、酵母肽0.17份、PQQ 0.01份、谷胱甘肽0.25份、姜黄素0.12份、茶多酚0.5份在洁净区称取原料，用混合机混合均匀，得到粉剂。成品按质量标准的规定取样进行各项指标的检验，检验合格后保存备用。
实施例4
按照重量配比为5’-尿苷酸0.6份、5’-腺苷酸0.6份、酵母肽0.25份、PQQ 0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份在洁净区称取原料，用混合机混合均匀，得到粉剂。成品按质量标准的规定取样进行各项指标的检验，检验合格后保存备用。
实施例5
按照重量配比为5’-尿苷酸0.3份、5’-腺苷酸0.3份、酵母肽0.17份、非瑟酮0.05份、PQQ 0.01份、谷胱甘肽0.25份、姜黄素0.12份、茶多酚0.5份在洁净区称取原料，用混合机混合均匀，得到粉剂。成品按质量标准的规定取样进行各项指标的检验，检验合格后保存备用。
实施例6
按照重量配比为5’-腺苷酸0.6份、5’-尿苷酸0.6份、酵母肽0.25份、α-硫辛酸0.05份、α-戊酮二酸0.3份、吡咯喹啉醌0.02份、姜黄素0.19份、非瑟酮0.1份、谷胱甘肽0.25份、白藜芦醇0.051份在洁净区称取原料，用混合机混合均匀，得到粉剂。成品按质量标准的规定取样进行各项指标的检验，检验合格后保存备用。
实施例7含有尿苷酸、腺苷酸和酵母肽的组合物的抗氧化性能
将实施例1制备的粉剂，准备称重后溶解于去离子水和乙醇的混合溶液中(体积比为1:1)，制得浓度为1mg/mL的母液，进行DPPH自由基清除率的测定和OH-自由基清除率的测定。
1.DPPH自由基清除率的测定：
将母液分别稀释100，50，25，10，1倍制备成浓度为10μg/mL，20μg/mL，40μg/mL，100μg/mL，500μg/mL的梯度稀释液。
分别取上述浓度150μL样品和150μL浓度为60mg/L的DPPH溶液(无水乙醇稀释)置于96孔板中，混合均匀，30℃避光保存，30min后使用酶标仪测量519nm下吸光度值。DPPH自由基清除率公式如下：
式中，A空白为150μL去离子水乙醇溶液和150μL DPPH溶液的吸光度，A样品为150μL样品和150μL DPPH溶液的吸光度；IC50为DPPH自由基清除率达到50％时样品的浓度。
2.OH-自由基清除率的测定：
(1)将母液分别稀释100，50，25，10，1倍制备成浓度为10μg/mL，20μg/mL，40μg/mL，100μg/mL，500μg/mL的梯度稀释液。
(2)分别取上述浓度50μL样品和50μL浓度为6mmol/L的FeSO4溶液，加入50μL浓度为6mmol/L的乙醇-水杨酸溶液，置于96孔板中，混合均匀后，加入50μL浓度为6mmol/L的H2O2溶液，混合均匀。
(3)在37℃条件下反应30min后将96孔板放入酶标仪测量510nm下吸光度值(A样品)。OH-自由基清除率公式如下：
式中，A空白为用DMSO代替体系中的样品的吸光度，A样品为50μL样品的吸光度。IC50为OH-自由基清除率达到50％时样品的浓度。
实施例2-6制备的粉剂样品参照上述方法检测DPPH自由基清除率和OH-自由基清除率。
对照组1：单组份5’-尿苷酸。
对照组2：单组份5’-腺苷酸。
对照组3：单组份酵母肽。
对照组4：5’-尿苷酸0.6份和5’-腺苷酸0.6份复配的组合物。
对照组5：5’-尿苷酸0.6份、5’-腺苷酸0.6份、酵母肽0.25份复配的组合物。
对照组6：5’-鸟苷酸0.6份、5’-胞苷酸0.6份、酵母肽0.25份复配的组合物。
对照组7：酵母肽0.25份、鹿茸提取物2份、PQQ 0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份。
对照组8：酵母肽0.25份、PQQ 0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份。
实验数据以均值±标准偏差表示，实验结果如表1所示。
表1含有尿苷酸、腺苷酸和酵母肽的组合物的抗氧化性能
结果表明，与对照组1-8相比，实施例1-6的含有尿苷酸、腺苷酸和酵母肽的组合物均具有较高的抗氧化性能，表现出更强的清楚DPPH自由基和OH-自由基的能力，尿苷酸和腺苷酸与酵母肽和功能活性成分复配后抗氧化性能呈现显著增强的效果，实施例1-6的组合物能够更有效的清除机体的自由基。
本发明将尿苷酸、腺苷酸、酵母肽和功能活性成分复配制备的组合物相较于单组份尿苷酸、单组份腺苷酸、单组份酵母肽、仅为酵母肽复配功能活性成分、两种核苷酸复配(5’-尿苷酸和5’-腺苷酸按重量比1:1复配)、两种核苷酸复配酵母肽(5’-尿苷酸：5’-腺苷酸：酵母肽按重量比0.6:0.6:0.25复配)或5’-鸟苷酸、5’-胞苷酸和酵母肽复配的混合物均具有显著的清除自由基的能力，清除DPPH自由基以及清除OH-自由基的能力得到明显提升。同时可以增强生物体中抗氧化酶的活性，达到延缓衰老的目的。尿苷酸和腺苷酸与酵母肽起到协同作用，增强了清除自由基的能力，复配功能活性成分后，效果得到进一步提升。
实施例8含有尿苷酸、腺苷酸和酵母肽的组合物体外延缓衰老性能
以人脐静脉内皮细胞、PC-12细胞(大鼠肾上腺嗜铬细胞瘤细胞)为模型，采用H2O2造模，对实施例1-6的组合物进行细胞内ROS水平的评价。
对照组1：单组份5’-尿苷酸。
对照组2：单组份5’-腺苷酸。
对照组3：单组份酵母肽。
对照组:4：5’-尿苷酸0.6份和5’-腺苷酸0.6份复配的组合物。
对照组5：5’-尿苷酸0.6份、5’-腺苷酸0.6份、酵母肽0.25份复配的组合物。
对照组6：5’-鸟苷酸0.6份、5’-胞苷酸0.6份、酵母肽0.25份复配的组合物。
对照组7：酵母肽0.25份、鹿茸提取物2份、PQQ 0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份。
对照组8：酵母肽0.25份、PQQ 0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份。
H2O2作用细胞后产生大量ROS，攻击细胞膜、蛋白质及核酸，导致细胞损伤。将对数生长期的细胞消化成单细胞悬液，调节细胞浓度为105个/mL，接种于96孔细胞培养板，每孔100μL，每组6个平行孔。接种24小时后，细胞贴壁生长，弃上清，加入终浓度200μmol/L的H2O2的培养基培养4h，然后替换为终浓度分别为50μg/mL的实施例1-6的组合物培养液继续培养24小时。实验同时设置不加H2O2的空白对照和只加H2O2的模型组，用活性氧检测试剂盒进行细胞内活性氧的状况评价：每孔加入10μmol/L的DCFH-DA母液(DMSO溶解)，终浓度为1μmol/L。继续培养2小时后，弃去上清，每孔加PBS 100μL洗涤2次，离心后使用200μL的PBS重悬细胞，使用荧光酶标仪于激发波长485nm，发射波长为525nm条件下测定各孔荧光强度，计算细胞的活性氧含量。实验数据以均值±标准偏差表示，实验结果如表2所示。
表2人脐静脉内皮细胞和PC-12细胞内的活性氧含量
上述结果表明，和模型组以及对照组1-8的组合物相比，实施例1-6的组合物能够显著降低模型细胞内的活性氧，实施例1-6的组合物对氧化损伤的细胞具有良好的保护和修复作用。
本发明将尿苷酸、腺苷酸、酵母肽和功能活性成分复配制备的组合物相较于单组份尿苷酸、单组份腺苷酸、单组份酵母肽、仅为酵母肽复配功能活性成分、两种核苷酸复配(5’-尿苷酸和5’-腺苷酸按重量比1:1复配)、两种核苷酸复配酵母肽(5’-尿苷酸：5’-腺苷酸：酵母肽按重量比0.6:0.6:0.25复配)或5’-鸟苷酸、5’-胞苷酸和酵母肽复配的混合物均具有显著的降低H2O2损伤的细胞内活性氧含量的能力，有助于使衰老氧化损伤的细胞得以修复，降低细胞内活性氧含量的能力得到显著提升。尿苷酸和腺苷酸与酵母肽起到协同作用，增强了降低细胞内活性氧的能力，复配功能活性成分后，效果得到进一步提升。
实施例9含有尿苷酸、腺苷酸和酵母肽的组合物对D-半乳糖诱导小鼠的作用
5周大的BALB/c小鼠，饲养一周后，其中20只用50mg/kg的D-半乳糖腹腔注射30天，30天后，以10只为一组。
实验组：分别按照实施例1-6的组合物灌胃共28天，并同时腹腔注射D-半乳糖。
对照组1：灌胃与组合物相同体积的5’-尿苷酸共28天，并同时腹腔注射D-半乳糖。
对照组2：灌胃与组合物相同体积的5’-腺苷酸共28天，并同时腹腔注射D-半乳糖。
对照组3：灌胃与组合物相同体积的酵母肽共28天，并同时腹腔注射D-半乳糖。
对照组4：灌胃与组合物相同体积的5’-尿苷酸0.6份和5’-腺苷酸0.6份复配的组合 物共28天，并同时腹腔注射D-半乳糖。
对照组5：灌胃与组合物体积相同的5’-尿苷酸0.6份、5’-腺苷酸0.6份、酵母肽0.25份复配的组合物共28天，并同时腹腔注射D-半乳糖。
对照组6：灌胃与组合物相同体积的5’-鸟苷酸0.6份、5’-胞苷酸0.6份、酵母肽0.25份复配的组合物共28天，并同时腹腔注射D-半乳糖。
对照组7：灌胃与组合物相同体积的酵母肽0.25份、鹿茸提取物2份、PQQ 0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份复配的组合物共28天，并同时腹腔注射D-半乳糖。
对照组8：灌胃与组合物相同体积的酵母肽0.25份、PQQ 0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份复配的组合物共28天，并同时腹腔注射D-半乳糖。
模型组：灌胃与组合物相同体积的PBS缓冲液。
空白组：腹腔注射与D-半乳糖同等剂量的生理盐水，30天后灌胃与组合物相同体积的PBS缓冲液，同时持续腹腔注射，共28天。
灌胃结束的第二天，眼眶采血后，用于后续实验。
实验结果如图1-图3所示，血清中氧化酶SOD和GSH-PX的含量均增加，丙二醛减少，说明本发明所述组合物能缓解D-半乳糖对小鼠的氧化损伤。与对照组1-8相比，实施例1-6所述的组合物均表现出更强的抗氧化损伤的能力，尿苷酸和腺苷酸与酵母肽协同作用，复配功能活性成分后，效果得到进一步提升。
实施例10尿苷酸、腺苷酸和酵母肽的组合物对自然衰老小鼠衰老的延缓作用
8周大的BALB/c小鼠，随机分为两组，每组10只，实验组：分别按照实施例1-6的组合物灌胃至小鼠衰老自然死亡。空白组：灌胃同等提及的生理盐水至小鼠衰老自然死亡。对照组1：灌胃与组合物相同体积的5’-尿苷酸至小鼠衰老自然死亡。对照组2：灌胃与组合物相同体积的5’-腺苷酸至小鼠衰老自然死亡。对照组3：灌胃与组合物相同体积的酵母肽至小鼠衰老自然死亡。对照组4：灌胃与组合物相同体积的5’-尿苷酸0.6份和5’-腺苷酸0.6份复配的组合物至小鼠衰老自然死亡。对照组5：灌胃与组合物体积相同的5’-尿苷酸0.6份、5’-腺苷酸0.6份、酵母肽0.25份复配的组合物至小鼠衰老自然死亡。对照组6：灌胃与组合物相同体积的5’-鸟苷酸0.6份、5’-胞苷酸0.6份、酵母肽0.25份复配的组合物至小鼠衰老自然死亡。对照组7：灌胃与组合物相同体积的酵母肽0.25份、鹿茸提取物2份、PQQ 0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白 藜芦醇0.051份复配的组合物至小鼠衰老自然死亡。对照组8：灌胃与组合物相同体积的酵母肽0.25份、PQQ 0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份复配的组合物至小鼠衰老自然死亡。
分别统计各组小鼠的生长寿命，结果如图4所示，本发明所述的含有尿苷酸、腺苷酸和酵母肽的组合物可以有效延缓小鼠自然衰老。
对于任何熟悉本领域的技术人员而言，在不脱离本发明技术方案范围情况下，都可利用上述揭示的技术内容对本发明技术方案作出许多可能的变动和修饰，或修改为等同变化的等效实施例。因此，凡是未脱离本发明技术方案的内容，依据本发明的技术实质对以上实施例所做的任何简单修改、等同变化及修饰，均应仍属于本发明技术方案保护的范围内。

Claims (9)

  1. 一种抗衰老的含有尿苷酸、腺苷酸和酵母肽的组合物，其特征在于，所述组合物包括5’-尿苷酸、5’-腺苷酸、酵母肽和功能活性成分，所述功能活性成分包括鹿茸提取物、吡咯喹啉醌、谷胱甘肽、姜黄素、茶多酚、槲皮素、白藜芦醇、α-硫辛酸、α-戊酮二酸、非瑟酮中的一种或者两种以上。
  2. 根据权利要求1所述的组合物，其特征在于，所述组合物中5’-尿苷酸、5’-腺苷酸、酵母肽和功能性成分包括如下重量份数组分：5’-腺苷酸0.3-1.2份、5’-尿苷酸0.3-1.2份、酵母肽0.05-1.5份、功能活性成分0.88-7.35份。
  3. 根据权利要求1所述的组合物，其特征在于，所述功能活性成分包括如下重量份数组分：鹿茸提取物1-2份、吡咯喹啉醌0.01-0.05份、谷胱甘肽0.25-1份、姜黄素0.12-0.6份、茶多酚0.5-1份、槲皮素0.5-1.25份、白藜芦醇0.02-0.1份、α-硫辛酸0.01-0.1份、α-戊酮二酸0.3-1份、非瑟酮0.05-0.25份中的一种或者两种以上。
  4. 根据权利要求1-3中任一项所述的组合物，其特征在于，所述组合物包括如下重量份数的组分：5’-腺苷酸0.6份、5’-尿苷酸0.6份、酵母肽0.25份、鹿茸提取物2份、吡咯喹啉醌0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份；或者所述组合物包括如下重量份数的组分：5’-腺苷酸0.6份、5’-尿苷酸0.6份、酵母肽0.25份、鹿茸提取物2份、α-硫辛酸0.05份、α-戊酮二酸0.3份、吡咯喹啉醌0.02份、姜黄素0.19份、非瑟酮0.1份、谷胱甘肽0.25份、白藜芦醇0.051份。
  5. 根据权利要求1-3中任一项所述的组合物，其特征在于，所述组合物包括如下重量份数的组分：5’-尿苷酸0.3份、5’-腺苷酸0.3份、酵母肽0.17份、吡咯喹啉醌0.01份、谷胱甘肽0.25份、姜黄素0.12份、茶多酚0.5份；或5’-尿苷酸0.6份、5’-腺苷酸0.6份、酵母肽0.25份、吡咯喹啉醌0.02份、谷胱甘肽0.25份、姜黄素0.19份、茶多酚0.5份、槲皮素0.5份、白藜芦醇0.051份；或5’-尿苷酸0.3份、5’-腺苷酸0.3份、酵母肽0.17份、非瑟酮0.05份、吡咯喹啉醌0.01份、谷胱甘肽0.25份、姜黄素0.12份、茶多酚0.5份；或5’-腺苷酸0.6份、5’-尿苷酸0.6份、酵母肽0.25份、α-硫辛酸0.05份、α-戊酮二酸0.3份、吡咯喹啉醌0.02份、姜黄素0.19份、非瑟酮0.1份、谷胱甘肽0.25份、白藜芦醇0.051份。
  6. 根据权利要求1、3或4所述的组合物，其特征在于，所述鹿茸提取物来源于新鲜鹿茸。
  7. 根据权利要求1-6中任一项所述的组合物，其特征在于，所述组合物的成品状态包括粉剂、颗粒剂、片剂、丸剂、口服液、胶囊。
  8. 权利要求1-7中任一项所述的含有尿苷酸、腺苷酸和酵母肽的组合物在制备抗衰老药品、保健品或营养食品中的应用。
  9. 根据权利要求8所述的应用，其特征在于，所述药品、保健品或营养食品具有清除体内自由基、抗氧化、对损伤细胞良好的保护和修复、延缓机体衰老、恢复年轻态的作用。
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