WO2023016389A1 - 包含β-烟酰胺单核苷酸和绿原酸的组合物及其应用 - Google Patents
包含β-烟酰胺单核苷酸和绿原酸的组合物及其应用 Download PDFInfo
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- chlorogenic acid
- nicotinamide mononucleotide
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Definitions
- the invention relates to a composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid and application thereof, belonging to the technical field of biomedicine.
- Cardiovascular disease is one of the non-communicable diseases with high morbidity and mortality worldwide. It is estimated that there are about 290 million CVD patients in my country at present. CVD includes various diseases, such as vascular disease, heart failure, coronary artery disease, myocardial ischemia, and hypertension. There are many factors that cause CVD, among which diabetes, hypertension, hyperlipidemia, obesity and other factors are the main causes of cardiovascular disease. At present, the three-high population in the market mainly uses drugs to regulate and control the three highs. Long-term use of drugs is likely to produce certain side effects. The composition of the prior art becomes an urgent problem to be solved. Studies have shown that natural products have good curative effects and application prospects in the protection of the cardiovascular system and the prevention and treatment of CVD.
- NMN ⁇ -nicotinamide mononucleotide
- 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.
- the effect of NMN alone needs to be further improved.
- the technical problem to be solved by the present invention is to provide a composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid, which has better weight loss, blood sugar lowering, blood pressure lowering and blood fat lowering effects.
- the present invention comprises the composition of ⁇ -nicotinamide mononucleotide and chlorogenic acid, and its active ingredient is composed of the following components by weight percentage: 30-70% of ⁇ -nicotinamide mononucleotide, and the rest is chlorogenic acid.
- the active ingredient of the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid consists of the following components in weight percentage: ⁇ -nicotinamide mononucleotide 40 ⁇ 60%, the rest is chlorogenic acid.
- the active ingredient of the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid consists of the following components in weight percentage: ⁇ -nicotinamide mononucleotide 60%, The rest is chlorogenic acid.
- the active ingredient of the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid consists of the following components in weight percentage: ⁇ -nicotinamide mononucleotide 50% , and the rest are chlorogenic acids.
- composition of the invention comprises ⁇ -nicotinamide mononucleotide and chlorogenic acid, and also includes food or pharmaceutically acceptable auxiliary materials.
- the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid is a granule, tablet, capsule, pill, ointment, drink or biscuit.
- the present invention also provides the application of the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid in the preparation of health products for reducing weight, blood sugar, blood pressure or blood fat.
- the present invention also provides the application of the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid in the preparation of medicines for reducing weight, blood sugar, blood pressure or blood fat.
- the present invention comprises the composition of ⁇ -nicotinamide mononucleotide and chlorogenic acid, the combination of ⁇ -nicotinamide mononucleotide and chlorogenic acid, the synergistic effect of the two can be applied in the preparation of weight loss, hypoglycemic,
- the health care products with the effect of lowering blood pressure or blood fat can also be used in the preparation of medicines with effects of reducing weight, blood sugar, blood pressure or blood fat.
- the present invention has the following beneficial effects:
- the present invention combines NMN and chlorogenic acid, and the two synergize, and have significant weight loss, blood sugar lowering, blood pressure lowering and blood lipid lowering effects.
- the composition of the invention has low cost and is easy to popularize.
- Fig. 1 is the influence of each group of medicines on fasting blood sugar in Test Example 1 of the present invention.
- Fig. 2 is the influence of each group of medicines on triglyceride in Test Example 1 of the present invention.
- Fig. 3 is the influence of each group of medicines on the amount of alanine aminotransferase in Test Example 1 of the present invention.
- Fig. 4 is the influence of each group of medicines on the amount of aspartate aminotransferase in Test Example 1 of the present invention.
- Fig. 5 is the therapeutic effect of the composition of Example 4 in Test Example 1 of the present invention on fatty liver.
- the present invention comprises the composition of ⁇ -nicotinamide mononucleotide and chlorogenic acid, and its active ingredient is composed of the following components by weight percentage: 30-70% of ⁇ -nicotinamide mononucleotide, and the rest is chlorogenic acid.
- Chlorogenic acid is one of the main active ingredients of many Chinese herbal medicines such as honeysuckle, eucommia, capillary, etc., and is also an important active ingredient in many fruits and vegetables. Studies have shown that chlorogenic acid has a wide range of biological activities, including lowering blood pressure, lowering blood lipids, antibacterial, antiviral, antitumor, scavenging free radicals and stimulating the central nervous system.
- composition of the present invention is composed of ⁇ -nicotinamide mononucleotide and chlorogenic acid, which are derived from the same origin of medicine and food. Weight loss, hypoglycemic, hypotensive and lipid-lowering effects. Moreover, the raw materials of the invention are easy to obtain, cheap, excellent in efficacy, non-toxic, and have no side effects, and are suitable for long-term use.
- the active ingredient of the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid consists of the following components in weight percentage: ⁇ -nicotinamide mononucleotide 40 ⁇ 60%, the rest is chlorogenic acid.
- the active ingredient of the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid consists of the following components in weight percentage: ⁇ -nicotinamide mononucleotide 60%, The rest is chlorogenic acid.
- the active ingredient of the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid consists of the following components in weight percentage: ⁇ -nicotinamide mononucleotide 50% , and the rest are chlorogenic acids.
- composition of the invention comprises ⁇ -nicotinamide mononucleotide and chlorogenic acid, and also includes food or pharmaceutically acceptable auxiliary materials.
- the dosage forms commonly used in this field can be prepared by adding auxiliary materials.
- the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid is a granule, tablet, capsule, pill, ointment, drink or biscuit.
- composition of the present invention comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid can be prepared by conventional methods. In one embodiment of the present invention, it can be prepared by the following method:
- the present invention also provides the application of the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid in the preparation of health products for reducing weight, blood sugar, blood pressure or blood fat.
- the present invention also provides the application of the composition comprising ⁇ -nicotinamide mononucleotide and chlorogenic acid in the preparation of medicines for reducing weight, blood sugar, blood pressure or blood fat.
- the present invention comprises the composition of ⁇ -nicotinamide mononucleotide and chlorogenic acid, the combination of ⁇ -nicotinamide mononucleotide and chlorogenic acid, the synergistic effect of the two can be applied in the preparation of weight loss, hypoglycemic,
- the health care products with the effect of lowering blood pressure or blood fat can also be used in the preparation of medicines with effects of reducing weight, blood sugar, blood pressure or blood fat.
- This embodiment provides a composition, the total mass of the composition is 25g, and the mass fraction of the main components of the composition is: ⁇ -nicotinamide mononucleotide 30%, chlorogenic acid 70%, weigh two raw materials, mix well.
- This embodiment provides a composition, the total mass of the composition is 25g, and the mass fraction of the main components of the composition is: 40% of ⁇ -nicotinamide mononucleotide and 60% of chlorogenic acid. raw materials, mix well.
- This embodiment provides a composition, the total mass of the composition is 25g, wherein the mass fraction of the main components of the composition is: ⁇ -nicotinamide mononucleotide 50%, chlorogenic acid 50%, weigh two raw materials, mix well.
- This embodiment provides a composition, the total mass of the composition is 25g, and the mass fraction of the main components of the composition is: ⁇ -nicotinamide mononucleotide 60%, chlorogenic acid 40%, weigh two raw materials, mix well.
- This embodiment provides a composition, the total mass of the composition is 25g, and the mass fraction of the main components of the composition is: 70% of ⁇ -nicotinamide mononucleotide and 30% of chlorogenic acid. raw materials, mix well.
- This embodiment provides a composition, the total mass of the composition is 25g, wherein the mass fraction of the main components of the composition is: ⁇ -nicotinamide mononucleotide 10%, chlorogenic acid 90%, weigh two raw materials, mix well.
- This embodiment provides a composition, the total mass of the composition is 25g, wherein the mass fraction of the main components of the composition is: ⁇ -nicotinamide mononucleotide 20%, chlorogenic acid 80%, weigh two raw materials, mix well.
- This embodiment provides a composition, the total mass of the composition is 25g, wherein the mass fraction of the main components of the composition is: ⁇ -nicotinamide mononucleotide 80%, chlorogenic acid 20%, weigh two raw materials, mix well.
- This embodiment provides a composition, the total mass of the composition is 25g, and the mass fraction of the main components of the composition is: 90% of ⁇ -nicotinamide mononucleotide and 10% of chlorogenic acid. raw materials, mix well.
- Test Example 1 Effect of Composition on Body Weight, Blood Sugar and Blood Lipid of Obese Mouse Model Induced by High Fat Diet
- mice Five-week-old C57BL/6J mice were used, half male and half male. Ten mice were randomly selected as the normal control group, fed with common feed, and the rest were fed with high-fat feed for 10 weeks. When fasting blood glucose ⁇ 6.8mmol/L and body weight greater than 35g, the mouse model was considered successful.
- the mice with successful modeling were randomly divided into 10 groups, and 100 mg/kg of the compositions of NMN, chlorogenic acid, Examples 1-5 and Comparative Examples 1-4 were given respectively, and the compositions were dissolved in 0.3 mL of normal saline.
- the blank control group and the normal control group were given the same volume of normal saline. At the same time, a positive drug rosiglitazone group (15 mg/kg) was set up.
- mice Dosing once a day for 8 consecutive weeks. The changes in body weight, food intake and body temperature of mice in different groups were recorded. After 8 weeks of treatment, the mice were killed, and blood biochemical indicators such as blood sugar, serum triglyceride, alanine aminotransferase, and aspartate aminotransferase were detected, and HE staining was performed on important organs such as the heart, liver, spleen, lung, and kidney.
- blood biochemical indicators such as blood sugar, serum triglyceride, alanine aminotransferase, and aspartate aminotransferase were detected, and HE staining was performed on important organs such as the heart, liver, spleen, lung, and kidney.
- Example 4 See Table 1 for the impact of the composition on the body weight of mice, see Figure 1 for the impact on fasting blood sugar, see Figure 2 for the impact on triglycerides, see Figure 3 for the impact on the amount of alanine aminotransferase, and see Figure 3 for the impact on the amount of aspartate aminotransferase 4.
- Normal represents the normal group
- NS represents the blank control group
- Rosi represents the rosiglitazone group
- CA represents the chlorogenic acid group
- E1 to E5 represent the groups of Example 1 to Example 5 respectively (that is, E1 is the composition of Example 1).
- C1 ⁇ C4 represent the comparative example 1 ⁇ 4 groups respectively (That is, C1 is the composition group of Comparative Example 1, C2 is the composition group of Comparative Example 2, C3 is the composition group of Comparative Example 3, and C4 is the composition group of Comparative Example 4).
- NMN and chlorogenic acid have certain effects on mouse body weight, blood sugar, triglycerides, alanine aminotransferase levels, and aspartate aminotransferase levels.
- the composition has obvious influence on the reduction of the above indicators.
- the composition of Example 4 has remarkable effects on weight loss, lowering blood sugar, lowering blood fat, reducing the amount of alanine aminotransferase and aspartate aminotransferase.
- Figure 5 the composition of Example 4 also has a significant therapeutic effect on fatty liver induced by a high-fat diet.
- the composition of Example 4 has significant weight-loss, blood sugar-lowering and blood-lipid-lowering effects.
- the antihypertensive effect of the composition of Example 4 was studied.
- SHR rats serum hypertensive rats
- WKY rats healthy homologous normotensive rats
- Rats were reared in separate cages, 5 in each cage, at room temperature (22 ⁇ 2)°C, natural light, relative humidity 60%-65%, and were given free access to water and food. After adaptive feeding for 2 weeks, the blood pressure of the rats was measured once a week.
- SHR rats 60 rats
- 60 SHR rats were randomly divided into normal saline group, cattolip group, NMN group, chlorogenic acid group, embodiment 4 low-dose group, embodiment 4 high-dose group, 10 in each group, another 10 were selected WKY rats were used as the control group, a total of seven groups.
- the NMN group was given 100 mg/kg of NMN
- the chlorogenic acid group was given 100 mg/kg of chlorogenic acid
- the high-dose group of Example 4 was given a composition of 100 mg/kg
- the low-dose group of Example 4 was given a composition of 50 mg/kg
- the captopril group was given 20 mg/kg captopril suspension
- the control group and normal saline group were given the same amount of normal saline.
- the body weight of each group was measured once a week, and the dosage of the next week was adjusted according to the body weight, and the administration was continued for 8 weeks.
- the BP-100A automatic non-invasive blood pressure measurement system was used to measure the tail artery blood pressure of the rats in the awake and resting state, and the average value was taken every week. The results are shown in Figure 6.
- the resulting composition achieves unexpected synergistic effects in terms of weight loss, blood sugar lowering, blood fat lowering and blood pressure lowering.
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Abstract
包含β-烟酰胺单核苷酸和绿原酸的组合物及其应用，该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（NMN）30～70％，其余为绿原酸。通过NMN与绿原酸复配，二者协同增效，具有减肥、降血糖、降血压和降血脂作用。
Description
本发明涉及包含β-烟酰胺单核苷酸和绿原酸的组合物及其应用，属于生物医药技术领域。
心血管疾病(Cardiovascular diseases，CVD)是目前全球发病率和病死率较高的非传染性疾病之一。据估计，目前我国约有2.9亿CVD患者。CVD包括各种疾病，如血管疾病、心力衰竭、冠状动脉疾病、心肌缺血和高血压等。引起CVD的因素有多种，其中糖尿病、高血压、高血脂、肥胖等因素是导致心血管疾病的主要原因。目前市场上的三高人群主要是通过药物进行三高的调理控制，长期服用药物易产生一定的副作用，因此，如何研发出一种在降低三高的同时达到无毒、无副作用，且效果显著的组合物成为现有技术亟需解决的问题。研究表明，天然产物在在心血管系统保护与CVD防治方面有较好的疗效和应用前景。
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。研究表明，NMN在降低小鼠体重、改善血糖血脂方面具有一定的作用。但是，单独的NMN，其效果有待进一步提高。
发明内容
针对以上缺陷，本发明解决的技术问题是提供一种包含β-烟酰胺单核苷酸和绿原酸的组合物，该组合物具有较好的减肥、降血糖、降血压和降血脂作用。
本发明包含β-烟酰胺单核苷酸和绿原酸的组合物，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30～70％，其余为绿原酸。
在本发明的一个具体实施方式中，所述包含β-烟酰胺单核苷酸和绿原酸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40～60％，其余为绿原酸。
在本发明的一个实施例中，所述包含β-烟酰胺单核苷酸和绿原酸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60％，其余为绿原酸。在本发明的另一个实施例中，所述包含β-烟酰胺单核苷酸和绿原酸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％，其余为绿原酸。
本发明包含β-烟酰胺单核苷酸和绿原酸的组合物，还包括食品或药品上可接受的辅料。
在本发明的一个实施方式中，所述包含β-烟酰胺单核苷酸和绿原酸的组合物为颗粒剂、片剂、胶囊、丸剂、膏剂、饮料或饼干。
本发明还提供本发明所述的包含β-烟酰胺单核苷酸和绿原酸的组合物在制备减肥、降血糖、降血压或降血脂的保健品中的应用。
本发明还提供本发明所述的包含β-烟酰胺单核苷酸和绿原酸的组合物在制备减肥、降血糖、降血压或降血脂的药品中的应用。
本发明包含β-烟酰胺单核苷酸和绿原酸的组合物，β-烟酰胺单核苷酸和绿原酸复配，二者协同增效，可以应用在制备具有减肥、降血糖、降血压或降血脂作用的保健品中，也可以应用在制备具有减肥、降血糖、降血压或降血脂作用的药品中。
与现有技术相比，本发明具有如下有益效果：
本发明通过NMN与绿原酸复配，二者协同增效，具有显著的减肥、降血糖、降血压和降血脂作用。此外，本发明组合物成本较低，便于推广。
图1为本发明试验例1中各组药物对空腹血糖的影响。
图2为本发明试验例1中各组药物对甘油三酯的影响。
图3为本发明试验例1中各组药物对谷丙转氨酶量的影响。
图4为本发明试验例1中各组药物对谷草转氨酶量的影响。
图5为本发明试验例1中的实施例4组合物对脂肪肝的治疗效果。
图6为本发明试验例2中实施例4组合物对大鼠收缩压和舒张压的影响(n＝10)。
本发明包含β-烟酰胺单核苷酸和绿原酸的组合物，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30～70％，其余为绿原酸。
绿原酸是许多中草药如金银花、杜仲、茵陈等的主要有效成分之一，也是众多水果蔬菜中的重要活性成分。研究表明，绿原酸具有广泛的生物活性，包括降血压、降血脂、抗菌、抗病毒、抗肿瘤、清除自由基和兴奋中枢神经系统等作用。
本发明组合物以来源于药食同源的原料β-烟酰胺单核苷酸和绿原酸组成，通过各 组分的相互配合及协同作用，达到协同增效的目的，使其具有显著的减肥、降血糖、降血压和降血脂作用。且本发明原料获取简单，价廉、效优，无毒、无副作用，适合长期使用。
在本发明的一个具体实施方式中，所述包含β-烟酰胺单核苷酸和绿原酸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40～60％，其余为绿原酸。
在本发明的一个实施例中，所述包含β-烟酰胺单核苷酸和绿原酸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60％，其余为绿原酸。在本发明的另一个实施例中，所述包含β-烟酰胺单核苷酸和绿原酸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％，其余为绿原酸。
本发明包含β-烟酰胺单核苷酸和绿原酸的组合物，还包括食品或药品上可接受的辅料。
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-烟酰胺单核苷酸和绿原酸的组合物为颗粒剂、片剂、胶囊、丸剂、膏剂、饮料或饼干。
本发明包含β-烟酰胺单核苷酸和绿原酸的组合物，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：
将β-烟酰胺单核苷酸、绿原酸和辅料混合均匀，得到所述包含β-烟酰胺单核苷酸和绿原酸的组合物。
本发明还提供本发明所述的包含β-烟酰胺单核苷酸和绿原酸的组合物在制备减肥、降血糖、降血压或降血脂的保健品中的应用。
本发明还提供本发明所述的包含β-烟酰胺单核苷酸和绿原酸的组合物在制备减肥、降血糖、降血压或降血脂的药品中的应用。
本发明包含β-烟酰胺单核苷酸和绿原酸的组合物，β-烟酰胺单核苷酸和绿原酸复配，二者协同增效，可以应用在制备具有减肥、降血糖、降血压或降血脂作用的保健品中，也可以应用在制备具有减肥、降血糖、降血压或降血脂作用的药品中。
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1
本实施例提供一种组合物，组合物的总质量为25g，其中组合物的主要组分质量分数为：β-烟酰胺单核苷酸30％，绿原酸70％，按比例称取两种原料，混合均匀。
实施例2
本实施例提供一种组合物，组合物的总质量为25g，其中组合物的主要组分质量分数为：β-烟酰胺单核苷酸40％，绿原酸60％，按比例称取两种原料，混合均匀。
实施例3
本实施例提供一种组合物，组合物的总质量为25g，其中组合物的主要组分质量分数为：β-烟酰胺单核苷酸50％，绿原酸50％，按比例称取两种原料，混合均匀。
实施例4
本实施例提供一种组合物，组合物的总质量为25g，其中组合物的主要组分质量分数为：β-烟酰胺单核苷酸60％，绿原酸40％，按比例称取两种原料，混合均匀。
实施例5
本实施例提供一种组合物，组合物的总质量为25g，其中组合物的主要组分质量分数为：β-烟酰胺单核苷酸70％，绿原酸30％，按比例称取两种原料，混合均匀。
对比例1
本实施例提供一种组合物，组合物的总质量为25g，其中组合物的主要组分质量分数为：β-烟酰胺单核苷酸10％，绿原酸90％，按比例称取两种原料，混合均匀。
对比例2
本实施例提供一种组合物，组合物的总质量为25g，其中组合物的主要组分质量分数为：β-烟酰胺单核苷酸20％，绿原酸80％，按比例称取两种原料，混合均匀。
对比例3
本实施例提供一种组合物，组合物的总质量为25g，其中组合物的主要组分质量分数为：β-烟酰胺单核苷酸80％，绿原酸20％，按比例称取两种原料，混合均匀。
对比例4
本实施例提供一种组合物，组合物的总质量为25g，其中组合物的主要组分质量分数为：β-烟酰胺单核苷酸90％，绿原酸10％，按比例称取两种原料，混合均匀。
试验例1 组合物对高脂饮食诱导的肥胖小鼠模型体重、血糖和血脂的影响
高脂饮食诱导的肥胖小鼠模型的建立：
采用5周龄C57BL/6J小鼠，雌雄各半。随机选取10只作为正常对照组，给予普 通饲料喂养，其余小鼠用高脂饲料喂养10周。当空腹血糖≥6.8mmol/L，体重大于35g时，认为该小鼠造模成功。将造模成功的小鼠随机分组，每组10只，分别给予NMN、绿原酸、实施例1～5和对比例1～4的组合物100mg/kg，组合物溶解于0.3mL生理盐水，空白对照组和正常对照组给予相同体积的生理盐水。同时设阳性药物罗格列酮组(15mg/kg)。每天给药1次，连续8周。记录不同组别小鼠体重、食量和体温的变化。治疗8周后，处死小鼠，检测血糖、血清甘油三脂、谷丙转氨酶、谷草转氨酶等血生化指标，并对重要脏器心、肝、脾、肺、肾做HE染色等。组合物对小鼠体重的影响见表1、对空腹血糖的影响见图1、对甘油三酯的影响见图2、对谷丙转氨酶量的影响见图3、对谷草转氨酶量的影响见图4，实施例4组合物对脂肪肝的治疗效果见图5。其中，Normal代表正常组、NS代表空白对照组、Rosi代表罗格列酮组、CA代表绿原酸组、E1～E5分别代表实施例1～实施例5组(即E1为实施例1组合物组，E2为实施例2组合物组，E3为实施例3组合物组，E4为实施例4组合物组，E5为实施例5组合物组)、C1～C4分别代表对比例1～4组(即C1为对比例1组合物组，C2为对比例2组合物组，C3为对比例3组合物组，C4为对比例4组合物组)。
表1组合物对小鼠体重的影响
由表1、图1～图4可知，NMN和绿原酸(CA)对小鼠体重、血糖、甘油三酯、谷丙转氨酶量、谷草转氨酶量有一定影响。随着NMN和绿原酸比例的变化，组合物对以上各指标减小具有明显的影响。特别是实施例4的组合物，减肥、降血糖、降血脂、降低谷丙转氨酶量、谷草转氨酶量的效果非常显著。由图5可知，实施例4组合物还对高脂饮食诱导的脂肪肝具有显著的治疗效果。
试验例2 组合物对大鼠血压的影响
根据试验例1的结果，实施例4的组合物与NMN和绿原酸相比，具有显著的减肥、降血糖和降血脂作用。本试验例对实施例4的组合物降血压作用进行研究。
(1)实验动物：
选择原发性高血压(SHR)大鼠80只和健康同源正常血压(WKY)大鼠10只，雌雄各半，体重(250±10)g。将大鼠分笼饲养，每笼5只，室温(22±2)℃，自然光照，相对湿度60％～65％，给予自由饮水、进食。适应性喂养2周后，每周测定大鼠血压1次。选择收缩压大于180mmHg(1mmHg＝0.133kPa)的SHR大鼠(60只)进行实验，另选择10只WKY大鼠作为空白对照。
(2)分组、给药与测定：
将60只SHR大鼠随机分为生理盐水组、卡托利普组、NMN组、绿原酸组、实施例4低剂量组、实施例4高剂量组，每组10只，另选择10只WKY大鼠作为对照组，共七组。NMN组给予100mg/kg的NMN、绿原酸组给予100mg/kg的绿原酸、实施例4高剂量组给予100mg/kg的组合物、实施例4低剂量组给予50mg/kg的组合物、卡托普利组每只给予20mg/kg卡托普利混悬液、对照组和生理盐水组给予等量的生理盐水。各组每周测量1次体质量，并根据体质量调整下周的给药量，连续给药8周。应用BP-100A全自动无创血压测量系统测量清醒静息状态下大鼠的尾动脉血压，每周1取平均值，结果见图6。
由图6可知，各给药组与模型组比较，从给药第2周开始收缩压和舒张压均有所下降，且随着给药时间的延长，其下降趋势更为明显，绿原酸的降血压效果优于NMN。本发明实施例4的组合物，低剂量下，对大鼠的收缩压和舒张压的降低能力稍逊于卡托普利组，而高剂量情况下，对大鼠的收缩压和舒张压的降低能力均优于卡托普利组，表明本发明的组合物具有非常好的降血压作用。
综上所述，将NMN与绿原酸复配后，所得组合物在减肥、降血糖、降血脂和降血压方面达到了意想不到的增效作用。
Claims (7)
- 包含β-烟酰胺单核苷酸和绿原酸的组合物，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30～70％，其余为绿原酸。
- 根据权利要求1所述的包含β-烟酰胺单核苷酸和绿原酸的组合物，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40～60％，其余为绿原酸。
- 根据权利要求1所述的包含β-烟酰胺单核苷酸和绿原酸的组合物，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60％，其余为绿原酸。
- 根据权利要求1～3任一项所述的包含β-烟酰胺单核苷酸和绿原酸的组合物，其特征在于：还包括食品或药品上可接受的辅料。
- 根据权利要求1～3任一项所述的包含β-烟酰胺单核苷酸和绿原酸的组合物，其特征在于：所述β-烟酰胺单核苷酸和绿原酸的组合物为颗粒剂、片剂、胶囊、丸剂、膏剂、饮料或饼干。
- 权利要求1～5任一项所述的包含β-烟酰胺单核苷酸和绿原酸的组合物在制备减肥、降血糖、降血压或降血脂的保健品中的应用。
- 权利要求1～5任一项所述的包含β-烟酰胺单核苷酸和绿原酸的组合物在制备减肥、降血糖、降血压或降血脂的药品中的应用。
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