WO2023000408A1 - COMPOSITION COMPRISING β-NICOTINAMIDE MONONUCLEOTIDE AND ROXBURGH ROSE EXTRACT, AND APPLICATION THEREOF - Google Patents
COMPOSITION COMPRISING β-NICOTINAMIDE MONONUCLEOTIDE AND ROXBURGH ROSE EXTRACT, AND APPLICATION THEREOF Download PDFInfo
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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 OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
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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 OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
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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 OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
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- 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
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/738—Rosa (rose)
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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
- 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
Definitions
- the invention relates to a composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract and application thereof, belonging to the technical field of biomedicine.
- microbial flora in the human intestinal tract. They interact to form a complex and relatively stable micro-ecosystem, and participate in many processes such as human immune regulation, biological antagonism, tumor suppression, lipid metabolism, and nutrient absorption. Human health plays a very important role. There are more than 1,000 types of microbial flora in the human gut, ten times the number of human cells. Under normal circumstances, the intestinal flora will maintain a relatively balanced state, but under the stimulation of some factors, it will lead to the imbalance of intestinal flora, which will lead to a variety of diseases, such as obesity, Alzheimer's disease, tumors, depression Wait. There are many factors that cause flora imbalance, including long-term and large-scale use of antibiotics, constipation, diet, living habits, environmental factors, and mental factors.
- the main way to improve the intestinal flora is to supplement probiotics.
- the live bacteria used in this method reach the intestinal tract through extreme environments such as gastric acid and bile after production, sale on the shelf, and consumption. Increase.
- NMN ⁇ -nicotinamide mononucleotide
- NMN ⁇ -nicotinamide mononucleotide
- Chinese patent CN111557949A discloses a composition of hydrogen-rich water and NMN. The results of this patent show that NMN, given to HFA mice at a dose of 22g/kg/day for 30 days, can improve intestinal bacteria to a certain extent. The role of the group. It can be seen that if NMN is used alone to improve the intestinal flora, the dosage is too large, resulting in high cost and affecting the promotion of use.
- Rosa roxburghii is a natural medicinal and edible plant, which is recorded in "Compendium of Materia Medica” and “Dictionary of Chinese Medicine”. Rosa roxburghii fruit is rich in nutrients such as flavonoids, polysaccharides, vitamins, superoxide dismutase (SOD) and organic acids, and has the functions of regulating immune function, delaying aging, anti-atherosclerosis and anti-tumor. Studies have shown that Rosa roxburghii polysaccharides can increase the abundance of beneficial bacteria and reduce the abundance of harmful bacteria in the intestinal tract of diabetic db/db mice to a certain extent, but have no significant effect on the diversity index and abundance of intestinal microorganisms (Wang et al. , Journal of Functional Foods, 2019, 52:408–417).
- the technical problem to be solved by the present invention is to provide a composition, which can improve the intestinal flora and anti-aging ability through the combination of ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract.
- composition of the present invention comprises ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract, and its active ingredient is composed of the following components by weight percentage: ⁇ -nicotinamide mononucleotide is 45-65%, and the rest is Rosa roxburghii extract things.
- the active ingredient of the composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract consists of the following components in weight percentage: ⁇ -nicotinamide mononucleotide 50 ⁇ 60%, and the rest is prickly pear extract.
- the active ingredient of the composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract consists of the following components by weight percentage: ⁇ -nicotinamide mononucleotide 50% , and the rest is Rosa roxburghii extract.
- the Rosa roxburghii extract described in the present invention is an aqueous extract.
- the present invention comprises a composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract, and also includes food acceptable excipients.
- the composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract is granule, tablet, capsule, pill, ointment, drink or biscuit.
- the present invention also provides the application of the composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract in the preparation of health care products or medicines for improving intestinal flora disturbance.
- composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract can improve intestinal flora, increase the number of lactobacilli and bifidobacteria, and help to improve intestinal flora disorder.
- the present invention also provides the application of the composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract in the preparation of anti-aging health products or medicines.
- composition of the invention comprising ⁇ -nicotinamide mononucleotide and roxburghii extract can prolong the lifespan of nematodes and delay aging.
- the present invention has the following beneficial effects:
- the invention combines NMN and Rosa roxburghii extract, and the two synergize to significantly improve intestinal flora and prolong the lifespan of nematodes, effectively improve intestinal flora disorder and delay aging.
- the composition of the invention has low cost and is easy to popularize.
- Fig. 1 is the community composition analysis (mean value) figure in Test Example 2 of the present invention, wherein, A figure is the relative abundance of intestinal flora on the phylum level; B figure is the relative abundance of intestinal flora on the genus level.
- Fig. 2 is an Alpha diversity analysis diagram of the mouse ileocecal flora in Test Example 2 of the present invention.
- Fig. 3 is a PCoA analysis diagram of the Beta diversity of the mouse ileocecal flora in Test Example 2 of the present invention.
- composition of the present invention comprises ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract, and its active ingredient is composed of the following components by weight percentage: ⁇ -nicotinamide mononucleotide is 45-65%, and the rest is Rosa roxburghii extract thing.
- the present invention achieves the purpose of mutual synergy through the specific ratio of ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract, thereby reducing the amount of NMN while enhancing the ability of the composition to improve intestinal flora and anti-aging .
- the active ingredient of the composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract consists of the following components in weight percentage: ⁇ -nicotinamide mononucleotide 50 ⁇ 60%, and the rest is prickly pear extract.
- the active ingredient of the composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract consists of the following components by weight percentage: ⁇ -nicotinamide mononucleotide 50% , and the rest is Rosa roxburghii extract.
- the Rosa roxburghii extract of the present invention is an aqueous extract.
- the Rosa roxburghii extract is rich in SOD, Rosa roxburghii polysaccharides, Rosa roxburghii polyphenols or vitamin C, and commercially available Rosa roxburghii extracts can be used.
- the invention comprises the composition of ⁇ -nicotinamide mononucleotide and roxburghii extract, and also includes food acceptable auxiliary materials.
- the dosage forms commonly used in this field can be prepared by adding auxiliary materials.
- the composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract is granule, tablet, capsule, pill, ointment, drink or biscuit.
- composition of the present invention comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract can be prepared by conventional methods. In one embodiment of the present invention, it can be prepared by the following method:
- composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract of the present invention can be used in the preparation of health products or medicines for improving intestinal flora disturbance.
- composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract can improve intestinal flora, increase the number of lactobacilli and bifidobacteria, and help to improve intestinal flora disorder.
- composition comprising ⁇ -nicotinamide mononucleotide and Rosa roxburghii extract of the present invention can be used in the preparation of anti-aging health care products or medicines.
- composition of the invention comprising ⁇ -nicotinamide mononucleotide and roxburghii extract can prolong the lifespan of nematodes and delay aging.
- Rosa roxburghii extract in the examples was purchased from Xi'an Ruilin Biotechnology Co., Ltd., and ⁇ -nicotinamide mononucleotide was self-made.
- This embodiment provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 50% of ⁇ -nicotinamide mononucleotide, 50% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
- This embodiment provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 60% of ⁇ -nicotinamide mononucleotide, 40% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
- This comparative example provides a composition, the total mass of the composition is 50g, and the mass fraction of the main components of the composition is: 10% of ⁇ -nicotinamide mononucleotide, 90% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
- This comparative example provides a composition, the total mass of the composition is 50g, and the mass fraction of the main components of the composition is: 20% of ⁇ -nicotinamide mononucleotide, 80% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
- This comparative example provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 30% of ⁇ -nicotinamide mononucleotide, 70% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
- This comparative example provides a composition, the total mass of the composition is 50g, and the mass fraction of the main components of the composition is: 40% of ⁇ -nicotinamide mononucleotide, 60% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
- This comparative example provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 70% of ⁇ -nicotinamide mononucleotide, 30% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
- This comparative example provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 80% of ⁇ -nicotinamide mononucleotide, 20% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
- This comparative example provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 90% of ⁇ -nicotinamide mononucleotide, 10% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
- Test Example 1 Effect of composition on intestinal flora of human flora (HFA) mouse model
- the HFA mice were randomly divided into 10 groups, and a blank solvent control group, a ⁇ -nicotinamide mononucleotide group, a Rosa roxburghii extract group, and the composition groups of Examples 1-2 and Comparative Examples 1-7 were set up.
- the dosages were all 100mg/kg, the samples were dissolved in normal saline, and 0.3mL was administered to each mouse.
- the mice were given regular gavage every day, and the blank solvent control group was gavaged with the same volume of normal saline every day for 21 consecutive days.
- the mice were free to eat and drink.
- the body weight changes of the mice in each group were recorded.
- mice After the mice were killed on the 22nd day, the contents of the cecum were collected aseptically, and the contents were placed in a sterile test tube. (g/V) was mixed with sterile physiological saline, and oscillated on a shaker for 15 minutes to obtain a suspension of intestinal contents. Take 6 test tubes containing 9 mL of sterilized physiological saline, and dilute the contents of the cecum in turn until the dilution factor is 10 -5 .
- the dilution of the sample was based on Bifidobacteria (10 -3 , 10 -4 , 10 -5 ), Lactobacillus (10 -3 , 10 -4 , 10 -5 ), Enterobacteriaceae (10 -2 , 10 -3 , 10 - 4 ), enterococci (10 -2 , 10 -3 , 10 -4 ), take 0.2mL samples of different dilutions with a pipette on different selection media, spread and culture, each dilution Culture medium to do 3 parallel plates.
- the culture conditions and identification methods of different intestinal flora are shown in Table 1.
- the conventional plate viable count method was used to count, and the average number of colonies ⁇ of the same dilution of various colonies was calculated, and the total number of colonies of samples with three dilutions of various colonies were calculated according to the formula, and the final result was expressed as colonies per gram of feces The logarithmic representation of the number. When counting, select a plate with 30-300 plate colonies.
- mice The body weight changes of the mice before and after the experiment and the number of bacteria in the intestinal tract of the mice are shown in Table 2.
- NMN had no significant effect on the intestinal flora of HFA mice, while Rosa roxburghii extract could increase the number of Lactobacillus and Bifidobacteria, and reduce the number of Enterobacteriaceae and the number of enterococci.
- Example 1 the composition of Example 1 has a significant improvement effect on the intestinal flora of HFA model mice.
- This test example will further investigate the reconstruction of the composition of Example 1 on the intestinal flora disorder induced by antibiotics effect.
- mice and 5 male mice were randomly left as the normal control group (Nor group), and the rest were given lincomycin hydrochloride solution by intragastric administration, 12 mL/kg, twice a day for 7 consecutive days. Give an equal volume of normal saline. After 7 days, 5 female mice and 5 male mice with diarrhea were respectively selected and killed as the model group (Mod group). The feces from the ileocecum of the mice were collected under sterile conditions, and the feces were observed for 16S rRNA detection. .
- mice Randomly group the mice with diarrhea, 10 in each group, set up the natural recovery group (Con), ⁇ -nicotinamide mononucleotide group (NMN, 100mg/kg), and Rosa roxburghii extract group (CL, 100mg/kg) And embodiment 1 composition high-dose (200mg/kg) group [NMN+CL (H)] and low-dose group (100mg/kg) [NMN+CL (L)], dissolve composition with physiological saline, each fill Stomach 0.3mL.
- the mice were given regular gavage every day, and the natural recovery group was gavaged with the same volume of normal saline every day for 7 consecutive days. During the feeding period, the mice were free to eat and drink.
- mice were killed on the 8th day, the feces from the ileocecum of each group were aseptically collected, and the feces properties were observed, and 16S rRNA was detected.
- the 16S rDNA V4 region of the sample is amplified.
- the amplification primer sequence is 515F (5'-GTGYCAGCMGCCGCGGTAA-3 ') and 806R (5'-GGACTACHVGGGTWTCTAAT-3').
- the target fragments are detected by electrophoresis, and the qualified samples are collected from the target bands for recovery, and a library is constructed for high-throughput sequencing.
- the sequencing results were spliced and filtered to obtain high-quality target sequences, and bioinformatics analysis was performed, including community composition analysis, Alpha diversity analysis, Beta diversity analysis, etc. The results are shown in Figures 1 to 3.
- low dosage group 100mg/kg
- high dosage group 200mg/kg
- All can make Bacteroidetes, thick
- the abundance of Bicobacteria and Proteobacteria recovered significantly, the abundance of Bacteroidetes increased, and the abundance of Proteobacteria and Firmicutes decreased. It shows that the combination of NMN and Rosa roxburghii extract effectively increases the content of beneficial bacteria in the intestinal tract of mice with dysbiosis, inhibits harmful bacteria, and makes the composition of intestinal flora tend to normal levels.
- Figure 2 shows the results of Alpha diversity analysis of mouse ileocecal flora. It can be seen from Figure 2 that after administration of lincomycin, the abundance and diversity of intestinal flora were significantly lower than those in normal mice. After administration of NMN and Rosa roxburghii extract, the abundance and diversity of the flora increased compared with the model group. After the composition of Example 1 is given, the low-dose group (100mg/kg) [NMN+CL (L) and the high-dose group (200mg/kg) [NMN+CL (H) can make the flora abundance and diversity Significantly improved sex.
- Figure 3 is the Beta diversity analysis of the ileocecal flora of mice. It can be seen from Figure 3 that after lincomycin treatment, the flora structure is significantly different from that of the normal group, and the flora diversity is reduced. After administration of NMN and Rosa roxburghii extract, the diversity of flora increased. After the composition of Example 1 is given, the low-dose group (100mg/kg) [NMN+CL (L) and the high-dose group (200mg/kg) [NMN+CL (H) can significantly improve the diversity of flora .
- NMN and Rosa roxburghii has a restoration and reconstruction effect on the intestinal flora of mice with antibiotic-induced flora dysbiosis.
- Experimental nematode strain wild-type nematode strain C.elegans Bristol N2
- Experimental medicinal solution and preparation method take NMN, roxburghii extract and the compositions of Example 1, Example 2 and Comparative Examples 1-7, add physiological saline to dissolve, and use a 0.22 ⁇ m water-based microporous filter membrane in an ultra-clean workbench Filter sterilize. Dispense into 1mL sterile EP tubes, seal with parafilm, and store in the refrigerator for later use. When in use, open the medicinal solution in an ultra-clean workbench, shake well, and dilute it with medium to a concentration of 100, 250 and 500 mg/mL.
- This experiment is divided into an experimental group and a control group.
- the synchronized Caenorhabditis elegans is cultured to the young adult stage in a biochemical incubator, and C. C. elegans to the NGM 6-well plate coated with OP50 bacteria, about 150 Caenorhabditis elegans per well, try to keep the size of the worm body consistent and the number of the experimental group and the control group should be consistent.
- a layer of medicinal solution was spread on the NGM plate coated with OP50 bacteria, and in the control group, the culture medium was spread flat.
- the method of judging the death of Caenorhabditis elegans 1. Gently touch the body of Caenorhabditis elegans with a platinum wire, and observe whether the Caenorhabditis elegans responds. 2. Observe under the microscope whether the pharynx of C. elegans twitches. The experimental results are shown in Table 3.
- NMN and Rosa roxburghii extract has synergistic effects, which can not only increase the abundance of beneficial bacteria, reduce the abundance of harmful bacteria, but also significantly increase the diversity index and abundance of intestinal microorganisms. It has an unexpected effect in improving the intestinal flora and delaying aging.
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Abstract
A composition comprising β-nicotinamide mononucleotide (NMN) and a roxburgh rose extract, and an application thereof, relating to the technical field of biomedicine. Provided are a composition comprising β-NMN and a roxburgh rose extract, and an application thereof. An active ingredient of the composition is composed of the following components in percentage by weight: β-NMN: 45-6%, and the remainder being the roxburgh rose extract. By compounding NMN with the roxburgh rose extract, the intestinal flora disorder is effectively improved, and the aging is delayed while reducing the amount of NMN.
Description
本发明涉及包含β-烟酰胺单核苷酸和刺梨提取物的组合物及其应用,属于生物医药技术领域。The invention relates to a composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract and application thereof, belonging to the technical field of biomedicine.
人体的肠道中存在种类繁多数目庞大的微生物菌群,它们相互作用,构成复杂且相对稳定的微生态系统,参与人体免疫调节、生物拮抗、抑制肿瘤、脂质代谢、营养吸收等众多过程,对人体健康有着十分重要的作用。人类肠道中的微生物菌群种类多达1000余种,数量是人体细胞数量的十倍。肠道菌群在正常情况下会保持相对平衡的状态,而在一些因素的刺激之下,会导致肠道菌群的失调,从而带来多种疾病,如肥胖、老年痴呆、肿瘤,抑郁症等。引起菌群失调的因素有很多包括长期、大量使用抗生素,以及便秘及饮食、生活习惯,还有环境因素以及精神因素。There are various and large numbers of microbial flora in the human intestinal tract. They interact to form a complex and relatively stable micro-ecosystem, and participate in many processes such as human immune regulation, biological antagonism, tumor suppression, lipid metabolism, and nutrient absorption. Human health plays a very important role. There are more than 1,000 types of microbial flora in the human gut, ten times the number of human cells. Under normal circumstances, the intestinal flora will maintain a relatively balanced state, but under the stimulation of some factors, it will lead to the imbalance of intestinal flora, which will lead to a variety of diseases, such as obesity, Alzheimer's disease, tumors, depression Wait. There are many factors that cause flora imbalance, including long-term and large-scale use of antibiotics, constipation, diet, living habits, environmental factors, and mental factors.
目前,改善肠道菌群的主要方法是补充益生菌。但是该方法使用的活菌从生产、在货架待售、食用后通过胃酸、胆汁等极端环境到达肠道——这层层考验均会消耗益生菌的活性,使益生菌的生产和保存成本大大增加。At present, the main way to improve the intestinal flora is to supplement probiotics. However, the live bacteria used in this method reach the intestinal tract through extreme environments such as gastric acid and bile after production, sale on the shelf, and consumption. Increase.
β-烟酰胺单核苷酸(简写为NMN)是一种自然存在的生物活性核苷酸,对人体细胞有重要的生理功能,能在细胞中天然合成,也可来源于多种食物如西兰花、卷心菜、黄瓜、毛豆等。中国专利CN111557949A公开了一种富氢水和NMN的组合物,该专利的结果表明,NMN在22g/kg/天的剂量下,连续灌胃给予HFA小鼠30天,具有一定的改善肠道菌群的作用。可以看出,若单独使用NMN改善肠道菌群,用量太大,导致成本高,影响推广使用。β-nicotinamide mononucleotide (abbreviated as NMN) is a naturally occurring bioactive nucleotide, which has important physiological functions for human cells, can be synthesized naturally in cells, and can also be derived from a variety of foods such as Western Orchids, cabbage, cucumbers, edamame, etc. Chinese patent CN111557949A discloses a composition of hydrogen-rich water and NMN. The results of this patent show that NMN, given to HFA mice at a dose of 22g/kg/day for 30 days, can improve intestinal bacteria to a certain extent. The role of the group. It can be seen that if NMN is used alone to improve the intestinal flora, the dosage is too large, resulting in high cost and affecting the promotion of use.
刺梨是一种天然的药食两用植物,《本草纲目》及《中药大辞典》均有收载。刺梨果实富含黄酮、多糖、维生素、超氧化物歧化酶(SOD)和有机酸等营养元素,具有调节机体免疫功能、延缓衰老、抗动脉粥样硬化和抗肿瘤等功能。研究表明,刺梨多糖能一定程度上提高糖尿病db/db小鼠肠道中有益菌的丰度,降低有害菌的丰度,但是对肠道微生物的多样性指数和丰度影响不显著(Wang等,Journal of Functional Foods,2019,52:408–417)。Rosa roxburghii is a natural medicinal and edible plant, which is recorded in "Compendium of Materia Medica" and "Dictionary of Chinese Medicine". Rosa roxburghii fruit is rich in nutrients such as flavonoids, polysaccharides, vitamins, superoxide dismutase (SOD) and organic acids, and has the functions of regulating immune function, delaying aging, anti-atherosclerosis and anti-tumor. Studies have shown that Rosa roxburghii polysaccharides can increase the abundance of beneficial bacteria and reduce the abundance of harmful bacteria in the intestinal tract of diabetic db/db mice to a certain extent, but have no significant effect on the diversity index and abundance of intestinal microorganisms (Wang et al. , Journal of Functional Foods, 2019, 52:408–417).
发明内容Contents of the invention
针对以上缺陷,本发明解决的技术问题是提供一种组合物,通过β-烟酰胺单核苷酸和刺梨提取物的组合,改善肠道菌群,提高抗衰老的能力。In view of the above defects, the technical problem to be solved by the present invention is to provide a composition, which can improve the intestinal flora and anti-aging ability through the combination of β-nicotinamide mononucleotide and Rosa roxburghii extract.
本发明包含β-烟酰胺单核苷酸和刺梨提取物的组合物,其活性成分由以下重量百分比的组分组成:β-烟酰胺单核苷酸45~65%,其余为刺梨提取物。The composition of the present invention comprises β-nicotinamide mononucleotide and Rosa roxburghii extract, and its active ingredient is composed of the following components by weight percentage: β-nicotinamide mononucleotide is 45-65%, and the rest is Rosa roxburghii extract things.
在本发明的一个实施方式中,所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物的活性成分由以下重量百分比的组分组成:β-烟酰胺单核苷酸50~60%,其余为刺梨提取物。In one embodiment of the present invention, the active ingredient of the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract consists of the following components in weight percentage: β-nicotinamide mononucleotide 50~ 60%, and the rest is prickly pear extract.
在本发明一个具体实施例中,所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物的活性成分由以下重量百分比的组分组成:β-烟酰胺单核苷酸50%,其余为刺梨提取物。In a specific embodiment of the present invention, the active ingredient of the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract consists of the following components by weight percentage: β-nicotinamide mononucleotide 50% , and the rest is Rosa roxburghii extract.
在本发明的一个实施方式中,本发明所述的刺梨提取物为水提物。In one embodiment of the present invention, the Rosa roxburghii extract described in the present invention is an aqueous extract.
在本发明的一个实施方式中,本发明包含β-烟酰胺单核苷酸和刺梨提取物的组合物,还包括食品上可接受的辅料。In one embodiment of the present invention, the present invention comprises a composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract, and also includes food acceptable excipients.
在本发明的一个实施方式中,所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物为颗粒剂、片剂、胶囊、丸剂、膏剂、饮料或饼干。In one embodiment of the present invention, the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract is granule, tablet, capsule, pill, ointment, drink or biscuit.
本发明还提供本发明所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物在制备改善肠道菌群紊乱的保健品或药品中的应用。The present invention also provides the application of the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract in the preparation of health care products or medicines for improving intestinal flora disturbance.
本发明包含β-烟酰胺单核苷酸和刺梨提取物的组合物,可以改善肠道菌群,增加乳酸杆菌和双歧杆菌数量,有助于改善肠道菌群紊乱。The composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract can improve intestinal flora, increase the number of lactobacilli and bifidobacteria, and help to improve intestinal flora disorder.
本发明还提供本发明所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物在制备延缓衰老的保健品或药品中的应用。The present invention also provides the application of the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract in the preparation of anti-aging health products or medicines.
本发明包含β-烟酰胺单核苷酸和刺梨提取物的组合物,可以延长线虫的寿命,延缓衰老。The composition of the invention comprising β-nicotinamide mononucleotide and roxburghii extract can prolong the lifespan of nematodes and delay aging.
与现有技术相比,本发明具有如下有益效果:Compared with the prior art, the present invention has the following beneficial effects:
本发明通过NMN与刺梨提取物复配,二者协同增效,显著改善肠道菌群和延长线虫的寿命,能有效改善肠道菌群紊乱、延缓衰老。此外,本发明组合物成本较低,便于推广。The invention combines NMN and Rosa roxburghii extract, and the two synergize to significantly improve intestinal flora and prolong the lifespan of nematodes, effectively improve intestinal flora disorder and delay aging. In addition, the composition of the invention has low cost and is easy to popularize.
图1为本发明试验例2中的群落组成分析(平均值)图,其中,A图为门水平上 肠道菌群相对丰度;B图为属水平上肠道菌群相对丰度。Fig. 1 is the community composition analysis (mean value) figure in Test Example 2 of the present invention, wherein, A figure is the relative abundance of intestinal flora on the phylum level; B figure is the relative abundance of intestinal flora on the genus level.
图2为本发明试验例2中小鼠回盲肠菌群的Alpha多样性分析图。Fig. 2 is an Alpha diversity analysis diagram of the mouse ileocecal flora in Test Example 2 of the present invention.
图3为本发明试验例2中小鼠回盲肠菌群Beta多样性PCoA分析图。Fig. 3 is a PCoA analysis diagram of the Beta diversity of the mouse ileocecal flora in Test Example 2 of the present invention.
本发明包含β-烟酰胺单核苷酸和刺梨提取物的组合物,其活性成分由以下重量百分比的组分组成:β-烟酰胺单核苷酸45~65%,其余为刺梨提取物。The composition of the present invention comprises β-nicotinamide mononucleotide and Rosa roxburghii extract, and its active ingredient is composed of the following components by weight percentage: β-nicotinamide mononucleotide is 45-65%, and the rest is Rosa roxburghii extract thing.
本发明通过β-烟酰胺单核苷酸和刺梨提取物的特定配比,达到互相协同增效的目的,从而在降低NMN用量的同时,增强组合物改善肠道菌群和抗衰老的能力。The present invention achieves the purpose of mutual synergy through the specific ratio of β-nicotinamide mononucleotide and Rosa roxburghii extract, thereby reducing the amount of NMN while enhancing the ability of the composition to improve intestinal flora and anti-aging .
在本发明的一个实施方式中,所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物的活性成分由以下重量百分比的组分组成:β-烟酰胺单核苷酸50~60%,其余为刺梨提取物。In one embodiment of the present invention, the active ingredient of the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract consists of the following components in weight percentage: β-nicotinamide mononucleotide 50~ 60%, and the rest is prickly pear extract.
在本发明一个具体实施例中,所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物的活性成分由以下重量百分比的组分组成:β-烟酰胺单核苷酸50%,其余为刺梨提取物。In a specific embodiment of the present invention, the active ingredient of the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract consists of the following components by weight percentage: β-nicotinamide mononucleotide 50% , and the rest is Rosa roxburghii extract.
本发明所述的刺梨提取物为水提物。该刺梨提取物富含SOD、刺梨多糖、刺梨多酚或维生素C等,可采用市售的刺梨提取物。The Rosa roxburghii extract of the present invention is an aqueous extract. The Rosa roxburghii extract is rich in SOD, Rosa roxburghii polysaccharides, Rosa roxburghii polyphenols or vitamin C, and commercially available Rosa roxburghii extracts can be used.
本发明包含β-烟酰胺单核苷酸和刺梨提取物的组合物,还包括食品上可接受的辅料。The invention comprises the composition of β-nicotinamide mononucleotide and roxburghii extract, and also includes food acceptable auxiliary materials.
可以通过添加辅料,来制成本领域常用的剂型。在本发明的一个实施方式中,所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物为颗粒剂、片剂、胶囊、丸剂、膏剂、饮料或饼干。The dosage forms commonly used in this field can be prepared by adding auxiliary materials. In one embodiment of the present invention, the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract is granule, tablet, capsule, pill, ointment, drink or biscuit.
本发明包含β-烟酰胺单核苷酸和刺梨提取物的组合物,可以通过常规方法制备,在本发明的一个实施方式中,可通过如下方法制备:The composition of the present invention comprising β-nicotinamide mononucleotide and Rosa roxburghii extract can be prepared by conventional methods. In one embodiment of the present invention, it can be prepared by the following method:
将β-烟酰胺单核苷酸、刺梨提取物和辅料混合均匀,得到所述包含β-烟酰胺单核苷酸和刺梨提取物组合物。Mix β-nicotinamide mononucleotide, Rosa roxburghii extract and auxiliary materials uniformly to obtain the composition containing β-nicotinamide mononucleotide and Rosa roxburghii extract.
本发明所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物,可在制备改善肠道菌群紊乱的保健品或药品中应用。The composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract of the present invention can be used in the preparation of health products or medicines for improving intestinal flora disturbance.
本发明包含β-烟酰胺单核苷酸和刺梨提取物的组合物,可以改善肠道菌群,增加乳酸杆菌和双歧杆菌数量,有助于改善肠道菌群紊乱。The composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract can improve intestinal flora, increase the number of lactobacilli and bifidobacteria, and help to improve intestinal flora disorder.
本发明所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物,可在制备延缓衰老的保健品或药品中应用。The composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract of the present invention can be used in the preparation of anti-aging health care products or medicines.
本发明包含β-烟酰胺单核苷酸和刺梨提取物的组合物,可以延长线虫的寿命,延缓衰老。The composition of the invention comprising β-nicotinamide mononucleotide and roxburghii extract can prolong the lifespan of nematodes and delay aging.
下面结合实施例对本发明的具体实施方式做进一步的描述,并不因此将本发明限制在所述的实施例范围之中。实施例中的刺梨提取物购自西安瑞林生物科技有限公司,β-烟酰胺单核苷酸自制。The specific implementation of the present invention will be further described below in conjunction with the examples, and the present invention is not limited to the scope of the examples. Rosa roxburghii extract in the examples was purchased from Xi'an Ruilin Biotechnology Co., Ltd., and β-nicotinamide mononucleotide was self-made.
实施例1Example 1
本实施例提供一种组合物,组合物的总质量为50g,其中组合物的主要组分质量分数为:β-烟酰胺单核苷酸50%,刺梨提取物50%,按比例称取两种原料,混合均匀。This embodiment provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 50% of β-nicotinamide mononucleotide, 50% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
实施例2Example 2
本实施例提供一种组合物,组合物的总质量为50g,其中组合物的主要组分质量分数为:β-烟酰胺单核苷酸60%,刺梨提取物40%,按比例称取两种原料,混合均匀。This embodiment provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 60% of β-nicotinamide mononucleotide, 40% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
对比例1Comparative example 1
本对比例提供一种组合物,组合物的总质量为50g,其中组合物的主要组分质量分数为:β-烟酰胺单核苷酸10%,刺梨提取物90%,按比例称取两种原料,混合均匀。This comparative example provides a composition, the total mass of the composition is 50g, and the mass fraction of the main components of the composition is: 10% of β-nicotinamide mononucleotide, 90% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
对比例2Comparative example 2
本对比例提供一种组合物,组合物的总质量为50g,其中组合物的主要组分质量分数为:β-烟酰胺单核苷酸20%,刺梨提取物80%,按比例称取两种原料,混合均匀。This comparative example provides a composition, the total mass of the composition is 50g, and the mass fraction of the main components of the composition is: 20% of β-nicotinamide mononucleotide, 80% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
对比例3Comparative example 3
本对比例提供一种组合物,组合物的总质量为50g,其中组合物的主要组分质量分数为:β-烟酰胺单核苷酸30%,刺梨提取物70%,按比例称取两种原料,混合均匀。This comparative example provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 30% of β-nicotinamide mononucleotide, 70% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
对比例4Comparative example 4
本对比例提供一种组合物,组合物的总质量为50g,其中组合物的主要组分质量分数为:β-烟酰胺单核苷酸40%,刺梨提取物60%,按比例称取两种原料,混合均匀。This comparative example provides a composition, the total mass of the composition is 50g, and the mass fraction of the main components of the composition is: 40% of β-nicotinamide mononucleotide, 60% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
对比例5Comparative example 5
本对比例提供一种组合物,组合物的总质量为50g,其中组合物的主要组分质量分数为:β-烟酰胺单核苷酸70%,刺梨提取物30%,按比例称取两种原料,混合均匀。This comparative example provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 70% of β-nicotinamide mononucleotide, 30% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
对比例6Comparative example 6
本对比例提供一种组合物,组合物的总质量为50g,其中组合物的主要组分质量分数为:β-烟酰胺单核苷酸80%,刺梨提取物20%,按比例称取两种原料,混合均匀。This comparative example provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 80% of β-nicotinamide mononucleotide, 20% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
对比例7Comparative example 7
本对比例提供一种组合物,组合物的总质量为50g,其中组合物的主要组分质量分数为:β-烟酰胺单核苷酸90%,刺梨提取物10%,按比例称取两种原料,混合均匀。This comparative example provides a composition, the total mass of the composition is 50g, wherein the mass fraction of the main components of the composition is: 90% of β-nicotinamide mononucleotide, 10% of Rosa roxburghii extract, weighed in proportion Two ingredients, mix well.
试验例1 组合物对人源菌群(HFA)小鼠模型肠道菌群的影响Test Example 1 Effect of composition on intestinal flora of human flora (HFA) mouse model
(1)HFA小鼠模型的构建(1) Construction of HFA mouse model
选择一位健康志愿者,女,25岁,3个月内未服用任何抗生素。收集志愿者清晨第一次排出的新鲜粪便,无菌、厌氧条件下称取粪便加入到Wilkins-Chalgren厌氧菌肉汤中(粪便:肉汤=1g:9mL),振荡混匀,制成粪便悬液待用。取4周龄的KM小鼠,体重22±3g,雌雄各半。向每只KM小鼠灌胃给予上述粪便悬液0.3mL,培养21天,人肠道菌群在小鼠体内定植后获得HFA小鼠模型。HFA小鼠饲育于SPF动物房内,无菌鼠基饲料、无菌水饲育,实验期间自由摄食饮水。Choose a healthy volunteer, female, 25 years old, who has not taken any antibiotics within 3 months. Collect fresh feces from volunteers for the first time in the morning, weigh the feces under aseptic and anaerobic conditions and add them to Wilkins-Chalgren anaerobic broth (feces: broth = 1g: 9mL), shake and mix to prepare The stool suspension is ready for use. Take 4-week-old KM mice, weighing 22±3g, half male and half male. Each KM mouse was intragastrically administered with 0.3 mL of the above-mentioned feces suspension, cultured for 21 days, and the HFA mouse model was obtained after colonization of human intestinal flora in the mice. HFA mice were bred in SPF animal room, fed with sterile mouse-based feed and sterile water, and had free access to food and water during the experiment.
(2)组合物对HFA模型肠道菌群的影响(2) Effect of composition on intestinal flora of HFA model
将HFA小鼠随机分组,每组10只,设置空白溶剂对照组、β-烟酰胺单核苷酸组、刺梨提取物组及实施例1-2和对比例1-7的组合物组,给药剂量均为100mg/kg,样品用生理盐水溶解,每只灌胃0.3mL。实验期间,每天对小鼠进行定时灌胃,空白溶剂对照组每天灌胃同体积的生理盐水,连续灌胃21d,饲养期间小鼠自由摄食饮水。实验期间记录各组小鼠的体重变化,第22天处死小鼠后,无菌采集盲肠内容物,置内容物于无菌试管中,超净工作台上称取盲肠内容物,按照1:9(g/V)加无菌生理盐水混合,振荡器上振荡15min,得肠内容物悬液。取装有9mL灭菌生理盐水的试管6支,依次稀释盲肠内容物,直至稀释倍数为10
-5。样品稀释度按照双歧杆菌(10
-3、10
-4、10
-5)、乳酸杆菌(10
-3、10
-4、10
-5)、肠杆菌(10
-2、10
-3、10
-4)、肠球菌(10
-2、10
-3、10
-4),用移液器取不同稀释度的样品0.2mL于不同的选择培养基上,涂布培养,每个稀释度下每种培养基做3个平行板。不同肠道菌群的培养条件及鉴定方法见表1。
The HFA mice were randomly divided into 10 groups, and a blank solvent control group, a β-nicotinamide mononucleotide group, a Rosa roxburghii extract group, and the composition groups of Examples 1-2 and Comparative Examples 1-7 were set up. The dosages were all 100mg/kg, the samples were dissolved in normal saline, and 0.3mL was administered to each mouse. During the experiment, the mice were given regular gavage every day, and the blank solvent control group was gavaged with the same volume of normal saline every day for 21 consecutive days. During the feeding period, the mice were free to eat and drink. During the experiment, the body weight changes of the mice in each group were recorded. After the mice were killed on the 22nd day, the contents of the cecum were collected aseptically, and the contents were placed in a sterile test tube. (g/V) was mixed with sterile physiological saline, and oscillated on a shaker for 15 minutes to obtain a suspension of intestinal contents. Take 6 test tubes containing 9 mL of sterilized physiological saline, and dilute the contents of the cecum in turn until the dilution factor is 10 -5 . The dilution of the sample was based on Bifidobacteria (10 -3 , 10 -4 , 10 -5 ), Lactobacillus (10 -3 , 10 -4 , 10 -5 ), Enterobacteriaceae (10 -2 , 10 -3 , 10 - 4 ), enterococci (10 -2 , 10 -3 , 10 -4 ), take 0.2mL samples of different dilutions with a pipette on different selection media, spread and culture, each dilution Culture medium to do 3 parallel plates. The culture conditions and identification methods of different intestinal flora are shown in Table 1.
表1 肠道菌群的培养条件及鉴定方法Table 1 Culture conditions and identification methods of intestinal flora
培养结束后,常规平板活菌计数法计数,计算出各种菌落同一稀释度的平均菌落数α,根据公式分别计算各种菌落3种稀释度样品的菌落总数,最终结果以每克粪便中菌落数的对数值表示。计数时选取平板菌落数为30~300个的平板。After the culture was completed, the conventional plate viable count method was used to count, and the average number of colonies α of the same dilution of various colonies was calculated, and the total number of colonies of samples with three dilutions of various colonies were calculated according to the formula, and the final result was expressed as colonies per gram of feces The logarithmic representation of the number. When counting, select a plate with 30-300 plate colonies.
菌落总数[l g(CFU/g)]=α×稀释倍数/0.1Total number of colonies [l g (CFU/g)] = α × dilution factor / 0.1
实验前后小鼠体重变化及小鼠肠道中细菌数量见表2。The body weight changes of the mice before and after the experiment and the number of bacteria in the intestinal tract of the mice are shown in Table 2.
表2 实验前后小鼠体重变化及小鼠肠道中细菌数量(n=10)Table 2 Changes in body weight of mice before and after the experiment and the number of bacteria in the intestinal tract of mice (n=10)
注:与溶剂对照组相比,*P<0.05,**P<0.01,***P<0.001Note: Compared with the solvent control group, *P<0.05, **P<0.01, ***P<0.001
由表2可知,与溶剂对照组相比,实验结束时小鼠体重均有增加。与溶剂组相比,NMN组和实施例1组合物组,小鼠体重明显低于溶剂组,表明NMN和实施例1、实施例2的组合物具有明显的减肥作用,且实施例1和实施例2的组合物减肥作用优于NMN。在改善肠道菌群方面,与溶剂组相比,100mg/kg时,NMN对HFA小鼠肠道菌群影响不明显,而刺梨提取物能增加乳酸杆菌和双歧杆菌数量,降低肠杆菌和肠球菌的数量。当NMN与刺梨提取物联用时,随着刺梨提取物比例的增加,肠道中乳酸杆菌和双歧杆菌数量呈先增加,后降低的趋势,而肠道中的肠杆菌和肠球菌呈先降低后增加的趋势,特别是实施例1和实施例2的组合物,与溶剂组相比,乳酸杆菌和双歧杆菌数量增加差异性极显著。由此可知,NMN与刺梨提取物联用后,协同增效,对HFA模型小鼠的肠道菌群起到了意想不到的改善效果。It can be seen from Table 2 that, compared with the solvent control group, the body weight of the mice increased at the end of the experiment. Compared with solvent group, NMN group and embodiment 1 composition group, mouse body weight is obviously lower than solvent group, show that NMN and embodiment 1, the composition of embodiment 2 have obvious weight-reducing effect, and embodiment 1 and implementation The weight loss effect of the composition of Example 2 is better than that of NMN. In terms of improving the intestinal flora, compared with the solvent group, at 100mg/kg, NMN had no significant effect on the intestinal flora of HFA mice, while Rosa roxburghii extract could increase the number of Lactobacillus and Bifidobacteria, and reduce the number of Enterobacteriaceae and the number of enterococci. When NMN was combined with Rosa roxburghii extract, with the increase of the ratio of Rosa roxburghii extract, the number of Lactobacillus and Bifidobacteria in the intestinal tract first increased and then decreased, while the number of Enterobacteriaceae and Enterococcus in the intestinal tract decreased first After the increasing trend, especially the compositions of Example 1 and Example 2, compared with the solvent group, the difference in the increase in the number of lactobacilli and bifidobacteria is extremely significant. It can be seen that the combination of NMN and Rosa roxburghii extract has a synergistic effect, which has an unexpected improvement effect on the intestinal flora of HFA model mice.
试验例2 组合物对抗生素诱导的肠道菌群紊乱的重建作用Test Example 2 Reconstitution Effect of Composition on Antibiotic-Induced Intestinal Flora Disorder
根据试验例1,实施例1的组合物对HFA模型小鼠的肠道菌群具有显著的改善作用,本试验例将进一步考察实施例1的组合物对抗生素诱导的肠道菌群紊乱的重建作用。According to Test Example 1, the composition of Example 1 has a significant improvement effect on the intestinal flora of HFA model mice. This test example will further investigate the reconstruction of the composition of Example 1 on the intestinal flora disorder induced by antibiotics effect.
(1)小鼠肠道菌群失调模型建立(1) Establishment of a mouse intestinal flora dysbiosis model
取4周龄KM小鼠,雌雄各半,体重22±3g,适应性喂养一周后开始实验。随机留下5只雌鼠和5只雄鼠作为正常对照组(Nor组),其余灌胃给予盐酸林可霉素溶液,12mL/kg,每天2次,连续7天,正常对照组通过灌胃方式给予等体积的生理盐水。7d后,将腹泻的小鼠分别选取5只雌鼠和5只雄鼠,处死,作为模型组(Mod组),无 菌条件下收集小鼠回盲肠部位粪便,并观察粪便性状,进行16S rRNA检测。Take 4-week-old KM mice, half male and half female, weighing 22±3g, and start the experiment after one week of adaptive feeding. 5 female mice and 5 male mice were randomly left as the normal control group (Nor group), and the rest were given lincomycin hydrochloride solution by intragastric administration, 12 mL/kg, twice a day for 7 consecutive days. Give an equal volume of normal saline. After 7 days, 5 female mice and 5 male mice with diarrhea were respectively selected and killed as the model group (Mod group). The feces from the ileocecum of the mice were collected under sterile conditions, and the feces were observed for 16S rRNA detection. .
(2)小鼠分组及药物处理(2) Grouping of mice and drug treatment
将拉肚子的小鼠随机分组,每组10只,设置自然恢复组(Con)、β-烟酰胺单核苷酸组(NMN,100mg/kg)、刺梨提取物组(CL,100mg/kg)及实施例1组合物高剂量(200mg/kg)组[NMN+CL(H)]和低剂量组(100mg/kg)[NMN+CL(L)],用生理盐水溶解组合物,每只灌胃0.3mL。实验期间,每天对小鼠进行定时灌胃,自然恢复组每天灌胃同体积的生理盐水,连续灌胃7d,饲养期间小鼠自由摄食饮水。实验期间记录各组小鼠的体重变化,第8天处死小鼠后,无菌收集各组回盲肠部位粪便,并观察粪便性状,进行16S rRNA检测。Randomly group the mice with diarrhea, 10 in each group, set up the natural recovery group (Con), β-nicotinamide mononucleotide group (NMN, 100mg/kg), and Rosa roxburghii extract group (CL, 100mg/kg) And embodiment 1 composition high-dose (200mg/kg) group [NMN+CL (H)] and low-dose group (100mg/kg) [NMN+CL (L)], dissolve composition with physiological saline, each fill Stomach 0.3mL. During the experiment, the mice were given regular gavage every day, and the natural recovery group was gavaged with the same volume of normal saline every day for 7 consecutive days. During the feeding period, the mice were free to eat and drink. During the experiment, the weight changes of the mice in each group were recorded. After the mice were killed on the 8th day, the feces from the ileocecum of each group were aseptically collected, and the feces properties were observed, and 16S rRNA was detected.
(3)肠道微生物高通量测序及其菌群分析(3) High-throughput sequencing of intestinal microorganisms and analysis of their flora
使用特定DNA提取试剂盒对小鼠粪便样本进行总基因组DNA抽提,检测DNA完整性和浓度之后,对样本的16S rDNA V4区域进行扩增,扩增引物序列为515F(5’-GTGYCAGCMGCCGCGGTAA-3’)和806R(5‘-GGACTACHVGGGTWTCTAAT-3’)。扩增后对目的片段进行电泳检测,检测合格的样品取目的条带进行回收,构建文库进行高通量测序。测序结果经过拼接过滤,得到高质量目标序列,进行生物信息学分析,包括群落组成分析,Alpha多样性分析,Beta多样性分析等分析,结果见图1~图3。Use a specific DNA extraction kit to extract total genomic DNA from mouse feces samples. After detecting DNA integrity and concentration, the 16S rDNA V4 region of the sample is amplified. The amplification primer sequence is 515F (5'-GTGYCAGCMGCCGCGGTAA-3 ') and 806R (5'-GGACTACHVGGGTWTCTAAT-3'). After amplification, the target fragments are detected by electrophoresis, and the qualified samples are collected from the target bands for recovery, and a library is constructed for high-throughput sequencing. The sequencing results were spliced and filtered to obtain high-quality target sequences, and bioinformatics analysis was performed, including community composition analysis, Alpha diversity analysis, Beta diversity analysis, etc. The results are shown in Figures 1 to 3.
由图1的A可以看出,在门水平上,正常组回盲肠中以拟杆菌门、厚壁菌门和变形菌门为主要菌门。灌服林可霉素后,导致小鼠回盲肠中拟杆菌门丰度急剧下降,变形菌门和厚壁菌门丰度大幅提升。灌服NMN或刺梨提取物后,拟杆菌门、厚壁菌门和变形菌门的丰度有所恢复。当给予实施例1的组合物后,低剂量组(100mg/kg)[NMN+CL(L)和高剂量组(200mg/kg)[NMN+CL(H)均能显著使拟杆菌门、厚壁菌门和变形菌门的丰度显著恢复,拟杆菌门丰度提高,变形菌门和厚壁菌门丰度下降。表明NMN和刺梨提取物的组合物有效增加了菌群失调小鼠肠道中有益菌的含量,抑制了有害菌,使肠道菌群组成趋于正常水平。It can be seen from A in Figure 1 that at the phylum level, Bacteroidetes, Firmicutes and Proteobacteria were the main phyla in the ileocecum of the normal group. After administration of lincomycin, the abundance of Bacteroidetes in the ileocecum of mice decreased sharply, and the abundance of Proteobacteria and Firmicutes increased significantly. The abundance of Bacteroidetes, Firmicutes and Proteobacteria recovered after feeding with NMN or Rosa roxburghii extract. After giving the composition of embodiment 1, low dosage group (100mg/kg) [NMN+CL (L) and high dosage group (200mg/kg) [NMN+CL (H) all can make Bacteroidetes, thick The abundance of Bicobacteria and Proteobacteria recovered significantly, the abundance of Bacteroidetes increased, and the abundance of Proteobacteria and Firmicutes decreased. It shows that the combination of NMN and Rosa roxburghii extract effectively increases the content of beneficial bacteria in the intestinal tract of mice with dysbiosis, inhibits harmful bacteria, and makes the composition of intestinal flora tend to normal levels.
由图1的B可以看出,经林可霉素处理后,在属水平上,小鼠回盲肠的拟杆菌属、副拟杆菌属、艾克曼菌属、肠杆菌属和毛螺菌属的丰度显著下降,葡萄球菌属和假单胞菌属的丰度大大增加。灌服NMN和刺梨提取物后,回盲肠部拟杆菌属和艾克曼菌属的丰度得到部分提升。当给予实施例1的组合物后,低剂量组(100mg/kg)[NMN+CL (L)和高剂量组(200mg/kg)[NMN+CL(H)均能显著使有益菌拟杆菌属、副拟杆菌属、艾克曼菌属、毛螺菌属等的丰度显著提升,有害菌如假单胞菌属、葡萄球菌属等丰度明显抑制。表明NMN和刺梨的组合物能有效提升小鼠肠道中的有益菌,抑制肠道中的有害菌。It can be seen from B of Figure 1 that after treatment with lincomycin, at the genus level, Bacteroides, Parabacteroides, Ekmansia, Enterobacter and Lachnospira in the ileocecum of mice The abundance of Staphylococcus and Pseudomonas significantly increased. The abundance of Bacteroides and Ekmansia in the ileocecum was partially increased after administration of NMN and Rosa roxburghii extract. After giving the composition of embodiment 1, low dosage group (100mg/kg) [NMN+CL (L) and high dosage group (200mg/kg) [NMN+CL (H) all can make beneficial bacteria Bacteroides , Parabacteroides, Ekmania, and Lachnospira significantly increased, while the abundance of harmful bacteria such as Pseudomonas and Staphylococcus was significantly suppressed. It shows that the composition of NMN and Rosa roxburghii can effectively promote the beneficial bacteria in the intestinal tract of mice and inhibit the harmful bacteria in the intestinal tract.
图2是小鼠回盲肠菌群的Alpha多样性分析结果。从图2可以看出,灌服林可霉素后,肠道菌群丰度和多样性均大大低于正常小鼠。给予NMN和刺梨提取物后,菌群丰度和多样性较模型组有所提升。当给予实施例1的组合物后,低剂量组(100mg/kg)[NMN+CL(L)和高剂量组(200mg/kg)[NMN+CL(H)均能使菌群丰度和多样性显著提升。Figure 2 shows the results of Alpha diversity analysis of mouse ileocecal flora. It can be seen from Figure 2 that after administration of lincomycin, the abundance and diversity of intestinal flora were significantly lower than those in normal mice. After administration of NMN and Rosa roxburghii extract, the abundance and diversity of the flora increased compared with the model group. After the composition of Example 1 is given, the low-dose group (100mg/kg) [NMN+CL (L) and the high-dose group (200mg/kg) [NMN+CL (H) can make the flora abundance and diversity Significantly improved sex.
图3是小鼠回盲肠菌群的Beta多样性分析,由图3可知,林可霉素处理后,菌群结构与正常组差异明显,菌群多样性降低。给予NMN和刺梨提取物后,菌群多样性有所提升。当给予实施例1的组合物后,低剂量组(100mg/kg)[NMN+CL(L)和高剂量组(200mg/kg)[NMN+CL(H)均能使菌群多样性显著提升。Figure 3 is the Beta diversity analysis of the ileocecal flora of mice. It can be seen from Figure 3 that after lincomycin treatment, the flora structure is significantly different from that of the normal group, and the flora diversity is reduced. After administration of NMN and Rosa roxburghii extract, the diversity of flora increased. After the composition of Example 1 is given, the low-dose group (100mg/kg) [NMN+CL (L) and the high-dose group (200mg/kg) [NMN+CL (H) can significantly improve the diversity of flora .
综上所述,NMN和刺梨的组合物,对抗生素诱导的菌群失调小鼠的肠道菌群具有恢复重建作用。In summary, the combination of NMN and Rosa roxburghii has a restoration and reconstruction effect on the intestinal flora of mice with antibiotic-induced flora dysbiosis.
试验例3 组合物抗衰老活性测试Test Example 3 Composition anti-aging activity test
(1)实验材料(1) Experimental materials
实验线虫株系:野生型线虫株系C.elegans Bristol N2Experimental nematode strain: wild-type nematode strain C.elegans Bristol N2
实验菌株:尿嘧啶缺陷型大肠杆菌(OP50),此类菌株无法自身合成尿嘧啶,自身生长所需的尿嘧啶需从固体培养基中摄取。Experimental strain: uracil-deficient Escherichia coli (OP50), which cannot synthesize uracil by itself, and the uracil required for its own growth needs to be taken from solid medium.
实验药液及配置方法:取NMN、刺梨提取物和实施例1、实施例2和对比例1-7的组合物,加生理盐水溶解,在超净工作台中用0.22μm水性微孔滤膜过滤除菌。分装至1mL无菌EP管中,用封口膜封住,放置于冰箱待用。使用时将药液于超净工作台中打开,摇匀,用培养基稀释至浓度为100、250和500mg/mL。Experimental medicinal solution and preparation method: take NMN, roxburghii extract and the compositions of Example 1, Example 2 and Comparative Examples 1-7, add physiological saline to dissolve, and use a 0.22 μm water-based microporous filter membrane in an ultra-clean workbench Filter sterilize. Dispense into 1mL sterile EP tubes, seal with parafilm, and store in the refrigerator for later use. When in use, open the medicinal solution in an ultra-clean workbench, shake well, and dilute it with medium to a concentration of 100, 250 and 500 mg/mL.
(2)秀丽隐杆线虫实验方法(2) Experimental method of Caenorhabditis elegans
本实验分为实验组和对照组,在生化培养箱中将同步化的秀丽隐杆线虫培养至年轻成虫期,在体视镜下用铂金丝挑取生长状态良好且虫体大小均匀地秀丽隐杆线虫至涂有OP50菌的NGM 6孔板中,每个孔约150只秀丽隐杆线虫,尽量保持虫体大小一致且实验组与对照组只数保持一致。实验组在涂有OP50菌的NGM板上平铺一层药 液,对照组则平铺培养基,此时按照线虫寿命天数第一天记录,前七天需要每天观察并转移秀丽隐杆线虫至新的干净的NGM 6孔板中,确保秀丽隐杆线虫的生活状态良好,食物充足,没有杂菌污染,第七天之后可以每隔一天转移一次,因为此时秀丽隐杆线虫几乎不再具备生殖能力,此时需要每天观察秀丽隐杆线虫的生长情况并记录秀丽隐杆线虫每天的死亡数目,包括正常死亡及非正常死亡,整理数据。判断秀丽隐杆线虫的死亡方法:1.用铂金丝轻轻碰触秀丽隐杆线虫身体,观察秀丽隐杆线虫是否有反应。2.在显微镜下观察秀丽隐杆线虫的咽部是否会抽动。实验结果见表3。This experiment is divided into an experimental group and a control group. The synchronized Caenorhabditis elegans is cultured to the young adult stage in a biochemical incubator, and C. C. elegans to the NGM 6-well plate coated with OP50 bacteria, about 150 Caenorhabditis elegans per well, try to keep the size of the worm body consistent and the number of the experimental group and the control group should be consistent. In the experimental group, a layer of medicinal solution was spread on the NGM plate coated with OP50 bacteria, and in the control group, the culture medium was spread flat. At this time, the lifespan of the nematode was recorded on the first day, and Caenorhabditis elegans should be observed and transferred to the new plant every day for the first seven days. elegans in a clean NGM 6-well plate to ensure that the living conditions of C. elegans are good, the food is sufficient, and there is no contamination by bacteria. After the seventh day, it can be transferred every other day, because at this time, C. elegans is almost no longer able to reproduce. At this time, it is necessary to observe the growth of Caenorhabditis elegans every day and record the number of deaths of Caenorhabditis elegans per day, including normal death and abnormal death, and organize the data. The method of judging the death of Caenorhabditis elegans: 1. Gently touch the body of Caenorhabditis elegans with a platinum wire, and observe whether the Caenorhabditis elegans responds. 2. Observe under the microscope whether the pharynx of C. elegans twitches. The experimental results are shown in Table 3.
表3 组合物对秀丽隐杆线虫寿命的影响Table 3 The effect of the composition on the lifespan of Caenorhabditis elegans
注:与溶剂对照组相比,*P<0.05,**P<0.01,***P<0.001Note: Compared with the solvent control group, *P<0.05, **P<0.01, ***P<0.001
由表3可知,NMN与刺梨提取物均能延长线虫寿命,但当NMN与刺梨提取物按照一定比例混合后,即使在NMN与刺梨提取物剂量分别减少一半的情况下,延长线虫寿命的活性均显著高于单独使用两者。It can be seen from Table 3 that both NMN and Rosa roxburghii extracts can prolong the lifespan of nematodes, but when NMN and Rosa roxburghii extracts are mixed according to a certain ratio, even if the doses of NMN and Rosa roxburghii extracts are reduced by half, the lifespan of nematodes can be extended The activities were significantly higher than the two alone.
综上所述,NMN与刺梨提取物联用后,协同增效,不仅能提高有益菌的丰度,降低有害菌的丰度,还能显著提高肠道微生物的多样性指数和丰度。在改善肠道菌群,延缓衰老方面,起到了意想不到的效果。In summary, the combination of NMN and Rosa roxburghii extract has synergistic effects, which can not only increase the abundance of beneficial bacteria, reduce the abundance of harmful bacteria, but also significantly increase the diversity index and abundance of intestinal microorganisms. It has an unexpected effect in improving the intestinal flora and delaying aging.
Claims (8)
- 包含β-烟酰胺单核苷酸和刺梨提取物的组合物,其特征在于,其活性成分由以下重量百分比的组分组成:β-烟酰胺单核苷酸45~65%,其余为刺梨提取物。The composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract is characterized in that its active ingredients are composed of the following components by weight percentage: β-nicotinamide mononucleotide is 45-65%, and the rest is thorn pear extract.
- 根据权利要求1所述的包含β-烟酰胺单核苷酸和刺梨提取物的组合物,其特征在于,其活性成分由以下重量百分比的组分组成:β-烟酰胺单核苷酸50~60%,其余为刺梨提取物。The composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract according to claim 1, wherein the active ingredient is composed of the following components by weight percentage: β-nicotinamide mononucleotide 50 ~60%, the rest is Rosa roxburghii extract.
- 根据权利要求1所述的包含β-烟酰胺单核苷酸和刺梨提取物的组合物,其特征在于,其活性成分由以下重量百分比的组分组成:β-烟酰胺单核苷酸50%,其余为刺梨提取物。The composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract according to claim 1, wherein the active ingredient is composed of the following components by weight percentage: β-nicotinamide mononucleotide 50 %, and the rest is Rosa roxburghii extract.
- 根据权利要求1~3任一项所述的包含β-烟酰胺单核苷酸和刺梨提取物的组合物,其特征在于:所述刺梨提取物为水提物。The composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract according to any one of claims 1 to 3, characterized in that: the Rosa roxburghii extract is a water extract.
- 根据权利要求1~3任一项所述的包含β-烟酰胺单核苷酸和刺梨提取物的组合物,其特征在于:还包括食品上可接受的辅料。The composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract according to any one of claims 1-3, characterized in that it also includes food acceptable auxiliary materials.
- 根据权利要求1~3任一项所述的包含β-烟酰胺单核苷酸和刺梨提取物的组合物,其特征在于:所述包含β-烟酰胺单核苷酸和刺梨提取物的组合物为颗粒剂、片剂、胶囊、丸剂、膏剂、饮料或饼干。The composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract according to any one of claims 1 to 3, characterized in that: the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract The composition is granule, tablet, capsule, pill, ointment, drink or biscuit.
- 权利要求1~6任一项所述的包含β-烟酰胺单核苷酸和刺梨提取物的组合物在制备改善肠道菌群紊乱的保健品或药品中的应用。Application of the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract according to any one of claims 1 to 6 in the preparation of health products or medicines for improving intestinal flora disturbance.
- 权利要求1~6任一项所述的包含β-烟酰胺单核苷酸和刺梨提取物的组合物在制备延缓衰老的保健品或药品中的应用。Application of the composition comprising β-nicotinamide mononucleotide and Rosa roxburghii extract described in any one of claims 1 to 6 in the preparation of anti-aging health products or medicines.
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Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102266043A (en) * | 2010-06-04 | 2011-12-07 | 钱立奎 | Novel production technology of nutrient health Rosa roxburghii solid beverage |
CN104814974A (en) * | 2015-03-16 | 2015-08-05 | 邦泰生物工程(深圳)有限公司 | Application of nicotinamide mononucleotide in preparation of anti-aging drugs or health care products |
CN106470687A (en) * | 2015-12-11 | 2017-03-01 | 邦泰生物工程(深圳)有限公司 | Nicotinamide mononucleotide. preparation prevent and treat arteriosclerosis, cardiovascular and cerebrovascular disease health product in application and its health product |
CN106617026A (en) * | 2016-10-24 | 2017-05-10 | 烟台燕园科玛健康产业有限公司 | Aging preventing food composition |
CN110338412A (en) * | 2019-07-16 | 2019-10-18 | 深圳市弘创农业科技有限公司 | The composition and its preparation of niacinamide-containing mononucleotide and ice plant and application |
CN111557949A (en) * | 2020-05-28 | 2020-08-21 | 深圳爱生生命科技有限公司 | Medicine or health product containing hydrogen-rich water and/or NMN and preparation method thereof |
DE202020105398U1 (en) * | 2020-09-21 | 2020-11-11 | BIODOMO Vertriebsgesellschaft für biologische Produkte mbH | Food supplement, capsule and packaging unit |
CN112089775A (en) * | 2020-10-30 | 2020-12-18 | 成都及禾生物科技有限公司 | NMN beneficial bacterium health composition and preparation method and application thereof |
CN112273649A (en) * | 2020-11-03 | 2021-01-29 | 深圳市新靶向生物科技有限公司 | Antioxidant and anti-aging composition, preparation method and application |
US20210077515A1 (en) * | 2020-10-12 | 2021-03-18 | Hangzhou Huadong Medicine Comprehensive Health Development Co., Ltd. | Compositions containing beta-nicotinamide mononucleotide and cordyceps sinensis and use thereof |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109674808A (en) * | 2019-01-30 | 2019-04-26 | 四川大学 | β-nicotinamide mononucleotide or its precursor are preparing the purposes delayed in lung senescence drug |
CN110974843A (en) * | 2019-12-23 | 2020-04-10 | 美益添生物医药(武汉)有限公司 | Composition and application thereof in balancing NO producing bacteria ratio in intestinal flora |
-
2021
- 2021-07-22 CN CN202110831357.4A patent/CN115671178A/en active Pending
- 2021-08-10 WO PCT/CN2021/111762 patent/WO2023000408A1/en active Application Filing
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102266043A (en) * | 2010-06-04 | 2011-12-07 | 钱立奎 | Novel production technology of nutrient health Rosa roxburghii solid beverage |
CN104814974A (en) * | 2015-03-16 | 2015-08-05 | 邦泰生物工程(深圳)有限公司 | Application of nicotinamide mononucleotide in preparation of anti-aging drugs or health care products |
CN106470687A (en) * | 2015-12-11 | 2017-03-01 | 邦泰生物工程(深圳)有限公司 | Nicotinamide mononucleotide. preparation prevent and treat arteriosclerosis, cardiovascular and cerebrovascular disease health product in application and its health product |
CN106617026A (en) * | 2016-10-24 | 2017-05-10 | 烟台燕园科玛健康产业有限公司 | Aging preventing food composition |
CN110338412A (en) * | 2019-07-16 | 2019-10-18 | 深圳市弘创农业科技有限公司 | The composition and its preparation of niacinamide-containing mononucleotide and ice plant and application |
CN111557949A (en) * | 2020-05-28 | 2020-08-21 | 深圳爱生生命科技有限公司 | Medicine or health product containing hydrogen-rich water and/or NMN and preparation method thereof |
DE202020105398U1 (en) * | 2020-09-21 | 2020-11-11 | BIODOMO Vertriebsgesellschaft für biologische Produkte mbH | Food supplement, capsule and packaging unit |
US20210077515A1 (en) * | 2020-10-12 | 2021-03-18 | Hangzhou Huadong Medicine Comprehensive Health Development Co., Ltd. | Compositions containing beta-nicotinamide mononucleotide and cordyceps sinensis and use thereof |
CN112089775A (en) * | 2020-10-30 | 2020-12-18 | 成都及禾生物科技有限公司 | NMN beneficial bacterium health composition and preparation method and application thereof |
CN112273649A (en) * | 2020-11-03 | 2021-01-29 | 深圳市新靶向生物科技有限公司 | Antioxidant and anti-aging composition, preparation method and application |
Non-Patent Citations (1)
Title |
---|
FAN CHUNXUE, DENG YULIN; ZHANG YAXI; XIN NIAN: "Research Progress on Pharmacological Activity of Rosa Roxburghii Tratt", LIFE SCIENCE INSTRUMENTS, SHENGMING KEXUE YIQI, CN, vol. 19, no. 2, 15 April 2021 (2021-04-15), CN , pages 14 - 21, XP093027147, ISSN: 1671-7929, DOI: 10.11967/2021190402 * |
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