WO2020029221A1 - 具有抑制脂肪形成及抗氧化活性的组合物及其用途 - Google Patents

具有抑制脂肪形成及抗氧化活性的组合物及其用途 Download PDF

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WO2020029221A1
WO2020029221A1 PCT/CN2018/099822 CN2018099822W WO2020029221A1 WO 2020029221 A1 WO2020029221 A1 WO 2020029221A1 CN 2018099822 W CN2018099822 W CN 2018099822W WO 2020029221 A1 WO2020029221 A1 WO 2020029221A1
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composition
group
fat
rhodiola rosea
inhibiting fat
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PCT/CN2018/099822
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English (en)
French (fr)
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黄福星
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黄福星
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Priority to JP2021531153A priority Critical patent/JP7197701B2/ja
Priority to CA3105317A priority patent/CA3105317C/en
Priority to PCT/CN2018/099822 priority patent/WO2020029221A1/zh
Publication of WO2020029221A1 publication Critical patent/WO2020029221A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9706—Algae
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/02—Preparation of oxygen-containing organic compounds containing a hydroxy group
    • C12P7/04—Preparation of oxygen-containing organic compounds containing a hydroxy group acyclic
    • C12P7/18—Preparation of oxygen-containing organic compounds containing a hydroxy group acyclic polyhydric
    • C12P7/20—Glycerol

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  • the present invention relates to a composition, and in particular to a composition having the activity of inhibiting fat formation and anti-oxidation and its use.
  • Human growth hormone is a peptide hormone secreted by the pituitary gland. Human growth hormone in the human body has the effects of helping tissue cells to repair and regenerate, maintaining the activation of various organs, increasing bone density, and reducing body fat and cholesterol. However, the amount of human growth hormone secreted in the human body will gradually decrease after 25 years of age, coupled with the effects of living stress and environmental degradation, leading to gradual decline of body functions and aging.
  • Rhodiola plants have the effects of anti-hypoxia, anti-fatigue, delaying aging and regulating the endocrine system, so many compounds for weight loss and anti-aging will add rhodiola.
  • U.S. Invention Patent Publication No. US9737580B2 which discloses a composition and method for improving brain function
  • the composition includes huperzine A, vinblastine, acetyl-L-carnitine and rhodiola. It has been clinically proven that in a specific preferred ratio, emotional cognition can be increased, and the purpose of controlling weight is achieved.
  • the ingredients of the above-mentioned disclosed composition can effectively regulate body weight, the main purpose is to enhance the brain function, thereby improving the effects of brain memory and emotional cognition, and it has not been clearly confirmed that the purpose of delaying functional aging can be achieved.
  • Taiwan Invention Patent Publication No. I441643 discloses a composition for regulating blood lipids and protecting the cardiovascular system.
  • the composition contains Rhodiola rosea powder, red yeast rice, plant alcohol, natto and vitamin B group. It has been proved that it can achieve the effects of adjusting blood lipids and protecting the cardiovascular system, and that it can significantly reduce body weight when given a specific proportion of dose; however, it has not been clearly proven that it can effectively achieve antioxidant effects.
  • the main purpose of the present invention is to solve the problems that the existing composition cannot simultaneously improve human body fat accumulation and functional aging.
  • the present invention provides a composition having an inhibitory effect on fat formation and antioxidant activity.
  • the composition includes an effective dose of Rhodiola rosea extract and monoglyceryl phosphate choline, and a pharmaceutically acceptable carrier or medicament. Accept salt.
  • Rhodiola rosea extract and glycerol phosphate choline ranges from 1: 1 to 1: 6.
  • the effective dose of the composition is 187 to 680 mg / kg body weight / day.
  • the weight ratio of Rhodiola rosea extract: glycerol phosphate choline ranges from 1: 3.
  • the effective dose of the composition is 384 mg / kg body weight / day.
  • composition also includes monoresveratrol.
  • the composition also includes a guanana.
  • composition is in the form of a capsule.
  • the composition is in the form of powder, granule or liquid.
  • Another embodiment of the present invention provides a use of the above composition for preparing a medicament for treating obesity.
  • Rhodiola rosea extract and choline glyceryl phosphate can effectively reduce the body weight and body fat of animals, and even enhance the antioxidant effect in animals, thereby achieving the purpose of effective weight loss and delaying aging .
  • FIG. 1 is an image diagram of hair follicle and subcutaneous fat staining on skin tissue of each group of subjects according to the present invention.
  • FIG. 2 is an image of immunostaining of skin tissue of each group of subjects according to the present invention.
  • the present invention provides a composition with inhibiting fat formation and antioxidant activity.
  • the composition comprises an effective dose of Rhodiola rosea extract and monoglyceryl phosphate choline and a pharmaceutically acceptable carrier or a pharmaceutically acceptable salt thereof.
  • Rhodiola is a perennial grass or shrub plant.
  • Rhodiola rosea extract contains a large amount of scopolamine, kaempferol and other antibacterial and anti-inflammatory ingredients, and also has anti-hypoxia, anti-fatigue, delay aging and regulate the endocrine system.
  • Glycerophosphocholine (alpha-GPC) is a small molecule nutrient. Glycerylphosphocholine is mainly found in human cells and breast milk, or can be obtained from non-transgenic soybeans by deacetylation technology and special ion exchange technology. Studies have shown that glyceryl phosphate choline can help tissue growth and reconstruction, organ activation, restore brain function without circulation, and maintain physiological functions such as brain attention, concentration, and memory. According to current clinical trial research, glyceryl phosphate choline can increase the concentration of choline and acetylcholine in the blood by oral means, and then reduce the cortison concentration, thereby achieving the purpose of further increasing the human growth hormone (hGH) concentration in the body.
  • hGH human growth hormone
  • the weight ratio of Rhodiola rosea extract: glycerol phosphate choline ranges from 1: 1 to 1: 6. In a preferred embodiment of the present invention, the weight ratio of Rhodiola rosea extract: glycerol phosphate choline ranges It is 1: 3.
  • the composition also includes a resveratrol and a guanana.
  • Resveratrol is widely present in many plants such as mulberry, peanuts, grapes, and especially the grape content is high. Studies have found that resveratrol has excellent antioxidant activity, which not only protects the human body from free radicals, but also produces antitoxins to fight against external invasions when plants are exposed to environmental stress, fungi and bacteria.
  • Guarana is an excitement stimulant that increases mental and muscle strength resistance, endurance, and can reduce physical and physical fatigue.
  • the xanthine in caffeine and caffeine in guarana provides the fastest and most stable thinking.
  • the composition of the present invention can be made into a powder, granule or liquid form, and can also be processed to further make the composition of the present invention into a capsule form; in particular, the capsule form can be an animal capsule or a plant Sex capsule.
  • Animal capsules can be made of gelatin, and vegetable capsules can be made of sodium carboxymethyl cellulose, which can be taken orally by users.
  • pharmaceutically acceptable salt as used in the present invention includes water-soluble and water-insoluble salts, which can retain the biological efficacy and properties of the composition.
  • pharmaceutically acceptable carrier as used in the present invention relates to a substance, composition or vehicle that transports or transfers a pharmaceutical preparation from one organ or part of the body to another organ or part of the body, which includes flavoring agents, Flavor enhancers, preservatives, antioxidants, chelating agents, penetrants, lubricants, lozenge adjuvants, colorants, humectants, binding agents, and equivalent carriers.
  • the examples of the present invention use animal experiments as verification to confirm that the composition of the present invention has the effects of inhibiting fat formation and antioxidant activity.
  • One subject of the experiment was from the National Laboratory Animal Center of the National Institutes of Health.
  • the subjects used 60 male C-8BL / 6 (B6) mice aged 6-8 weeks, with a starting weight of about 20 grams, and 10 subjects were tested. Or a group.
  • Each group of subjects was housed in an animal room at 22 ⁇ 2 ° C, and the light time and the dark time were controlled by timers, in which the light time and the dark time were 12 hours each. Since subjects usually eat during dark hours, the best time to remove the feed is when they start to turn bright, and the fasting time can be set to 12 ⁇ 2 hours.
  • the subjects were given a high-fat diet orally and D-galactose by injection. It is worth noting that high-fat feed is intended to induce obesity in the subject; excessive injection of D-galactose will cause a large amount of reactive oxygen species in the subject's body, thereby destroying the balance of the reactive oxygen species concentration in the body, thereby inducing The subject has a peroxidative effect.
  • Subjects between 6-8 weeks of age were randomly divided into six groups based on their weight, 10 in each group. Each subject was given a high-fat diet and injected with D-galactose in the animal room before each subject passed.
  • the composition containing Rhodiola rosea extract and choline glycerol phosphate was orally administered, and the experiment was performed for 12 weeks. The body weight was measured and recorded weekly during the experiment.
  • administration refers to the direct administration of a composition or a pharmaceutically acceptable salt of the composition to an individual, which can form an equivalent amount of the active composition in the body of the individual.
  • the experimental groups can be divided into: (1) normal group: normal feed was given freely, and sterile reverse osmosis water was given 10 ml / kg. (2) Control group: freely fed high-fat diet, subcutaneous injection of 0.3-1.2g / kg of D-galactose at the neck and back; given sterile reverse osmosis water 10ml / kg. (3) Experimental group 1: Free-fed high-fat diet, subcutaneous injection of 0.3-1.2g / kg D-galactose at the neck and back; 1 time dose of Rhodiola rosea extract, in which the content of Rhodiola rosea extract 88.4 mg / kg body weight / day.
  • test and control feeds must contain approximately equal amounts of calories, protein, fat, calcium and other minerals or vitamins.
  • Animal test results are converted into human recommended doses: the optimal effective dose is obtained by combining the statistical results of animal tests. If the unit is% in feed, the same% is the total human dietary intake (500 g dry in a day). Weight)% is a double dose. For example, when the best comprehensive result is obtained in a group containing 1% of the test product in the feed, it is considered that humans also ingest 1% (5 grams) as the best double dose. If the experiment is based on the unit weight per kg (/ kg b.w.), it will be multiplied by 60 kg as the effective dose for adults.
  • the body weight should be accurately weighed at least once a week (it should be fixed in the animal room every day before the light is dimmed and before feeding), and the weight change of each group of subjects is observed.
  • the conversion method of weight change is: weight change (end weight)-initial weight.
  • Table 1 is a weight change table of each group of subjects in this example.
  • the results in Table 1 show that as the experimental weeks increase, the average body weight of all experimental subjects has steadily increased. Among them, the average weight gain of the control group is the most significant; however, for the experimental groups 2 to 4, After administering the composition of the present invention, the average body weight of the test subjects was significantly lower than that of the control group.
  • the average body weight of the test subjects was significantly lower than that of the control group by about 7
  • the effect of gram it is obvious that the present invention can effectively reduce the weight of the subject by feeding the Rhodiola extract with a mixture of glycerol phosphate choline, and in addition, the Rhodiola extract is given by:
  • the experimental group 3 of 1: 3 has the best overall weight loss effect.
  • body fat percentage is as follows:
  • Body fat ratio [body fat mass (g) / body weight (g)] ⁇ 100%.
  • the body fat mass (g) paratesticular fat (g) + peripheral kidney fat (g) + mesenteric fat (g).
  • all animals should be treated by the same person in the same way in order to reduce body fat, so as to reduce errors among individual animals.
  • Table 2 for a table of changes in organ weight and body fat of each group of subjects in this embodiment.
  • the results in Table 2 show that after 12 weeks of the experiment, the body fat percentage and total fat of all experimental subjects have an increasing trend, among which, the increase in the control group is the most significant (P ⁇ 0.05); however, compared with For experimental groups 2 to 4, after the subjects were administered the composition of the present invention, their body fat percentage and total fat were significantly lower than those of the control group (P ⁇ 0.05); that is, the composition of the present invention Can effectively inhibit the effects of obesity and fat accumulation.
  • biochemical analysis was used to analyze various biochemical values of body fat function.
  • the biochemical analysis items are as follows:
  • Table 3 is a blood biochemical value change table for each group of subjects in this example.
  • the blood glucose results showed that the blood glucose concentration of the control group was significantly increased compared with the normal group (P ⁇ 0.05); however, the blood glucose concentrations of the experimental groups 1 to 4 were compared with the control The group decreased slightly.
  • Cholesterol results showed that the concentrations of cholesterol in the serum of the experimental groups 1 to 4 were significantly lower than those of the control group (P ⁇ 0.05).
  • Creatinine results showed that the creatinine concentration in the serum of the experimental groups 1 to 3 had a slight decrease trend compared with the control group.
  • the creatinine concentration of the experimental group 4 was significantly lower than that of the control group (P ⁇ 0.05).
  • the results of low-density lipoprotein (LDL) showed that the concentrations of low-density lipoprotein in experimental groups 1 to 4 were significantly lower than those in the control group (P ⁇ 0.05).
  • the results of high-density lipoprotein (HDL) showed that the concentration of high-density lipoprotein in experimental groups 1 to 4 was significantly higher than that in the control group (P ⁇ 0.05). Therefore, the experimental results in Table 3 show that the composition of the present invention can effectively inhibit multiple biochemical activities that form body fat, and effectively achieve the effect of reducing body fat rate.
  • Enzyme method and colorimetric principle were used to measure the concentration of superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and G6PD (Glucose-6-phosphate dehydrogenase) in serum.
  • SOD superoxide dismutase
  • GSHPx glutathione peroxidase
  • G6PD Glucose-6-phosphate dehydrogenase
  • Table 4 is a table of changes in blood antioxidant indexes of each group of subjects in this example.
  • SOD superoxide dismutase
  • GSH glutathione peroxidase
  • G6PD G6PD
  • the present invention can effectively improve the antioxidative effect by giving Rhodiola rosea extract and choline glycerol phosphate, thereby achieving the purpose of eliminating peroxidative molecules and free radicals in the body. It is experimentally confirmed that the experimental group 3 The antioxidant effect is the best, which in turn helps to delay the aging effect.
  • Human growth hormone (human growth hormone, hGH) analysis human growth hormone ELISA kit was used to analyze the hGH concentration in serum.
  • Table 5 is a growth hormone change table for each group of subjects in this embodiment.
  • the results of growth hormone in blood showed that the concentration of growth hormone in the serum of the control group was significantly lower than that of the normal group (P ⁇ 0.05), but the experimental group was 1 to 4 ratios. There was a significant increase in the control group (P ⁇ 0.05).
  • subject to the induction of aging and obesity by giving Rhodiola rosea extract and choline glycerol phosphate, it also relatively increased the effect of growth hormone in the body to achieve the effect of helping the subject lose weight. .
  • FIG. 1 is an image diagram of hair follicle and subcutaneous fat staining of skin tissue of each group of subjects in this embodiment.
  • the subjects in addition to the combination of Rhodiola rosea extract and choline glycerol phosphate, the subjects can effectively increase the skin's hair follicle tissue to increase the hair content, and can further reduce the thickness of the subendothelial fat. purpose.
  • FIG. 2 is an image diagram of immunostaining of skin tissue of each group of subjects in this embodiment.
  • the 4-HNE staining test in the control group has a significantly darker color than the normal group. Oxidation phenomenon; however, for experimental groups 2 to 4 after the test, the deposition amount color of 4-HNE staining was significantly lighter than that of the control group. It was measured that the color of the deposition amount of 4-HNE staining was lighter, and the staining area of the deposition amount was smaller, further indicating that the experimental group 3 had the best anti-oxidation effect; therefore, it represents the Rhodiola rosea extract of the present invention. In combination with glyceryl phosphate choline, the effect and purpose of improving the anti-peroxidation effect can be further achieved.
  • the present invention has confirmed through experiments that the combination of Rhodiola rosea extract and glyceryl phosphate choline can effectively reduce the body weight and body fat of the subject, and even enhance the anti-peroxidation effect in the body.
  • the combination ratio of Rhodiola rosea extract and glyceryl phosphate choline is 1: 3
  • the effect of inhibiting body fat, reducing weight and antioxidative effect is the best; therefore, the composition of the present invention can be used as
  • the preparation of a medicine for treating obesity can also improve the anti-peroxidation effect of tissues in the body and realize the effect of delaying aging.

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Abstract

提供一种具有抑制脂肪形成及抗氧化活性的组合物，组合物包括有效剂量的一红景天萃取物及一甘油磷酸胆碱及其医药可接受载剂或医药可接受盐。经动物实验证实，通过红景天萃取物与甘油磷酸胆碱的混合，能有效降低动物体内的体脂肪，还可提高抗氧化的效果。

Description

具有抑制脂肪形成及抗氧化活性的组合物及其用途 技术领域
本发明涉及一种组合物，尤指一种具有抑制脂肪形成及抗氧化活性的组合物及其用途。
背景技术
人类生长激素(human growth hormone，hGH)，是脑下垂体所分泌而成的胜肽类激素。人体内的人类生长激素具有帮助组织细胞的修补再生、维持各项器官活化的功能、提高骨质密度及降低体脂肪与胆固醇的效果。然而，人体内的人类生长激素的分泌量会在25岁之后逐年减少，加上生活压力与环境恶化影响，导致体内机能逐渐衰退及老化。
对于上述人体肥胖及机能老化的问题，可通过饮食及运动的方式改善，若无成效时，才需通过药物进行治疗。而且，许多学者为了达到抑制脂肪形成以及延缓老化的目的，进行多项生化实验。其中经研究发现，红景天植物中具有抗缺氧、抗疲劳、延缓衰老及调节内分泌系统的效果，因而许多减肥及抗老化的复方都会添加红景天的成分。
如美国发明专利公告号US9737580B2，其公开了一种提升脑功能的组合物及其方法，其组合物包括石杉碱甲，长春西汀，乙酰基-L-肉碱和红景天，其经临床证实，在特定优选的比例中可增加情绪的认知，而且达到控制体重为目的。然而，上述揭示组合物的成分虽能有效调控体重，但主要目的在于增强脑部功能，进而提升脑内记忆及情绪认知的效果，同样也并未明确证实能够达到延缓机能老化的目的。
又如中国台湾发明专利公告号I441643，揭示一种调整血脂及保护心血管的组合物，其组合物含有红景天复方粉、红曲、植物醇、纳豆及维生素B群，其经动物实验证实，能达到调整血脂及保护心血管的功效，而且，在给予特定比例剂量下，能显著地达到降低体重的效果；但也未明确证实能够有效达到抗氧化的效果。
发明内容
本发明的主要目的在于解决现有组成物无法同时改善人体脂肪堆积及机能老化的问题。
为达到上述目的，本发明提供一种具有抑制脂肪形成及抗氧化活性的组合物，组合物包括有效剂量的一红景天萃取物及一甘油磷酸胆碱及其医药可接受载剂或医药可接受盐。
其中，红景天萃取物：甘油磷酸胆碱间的重量比例范围为1：1至1：6。
其中，红景天萃取物：甘油磷酸胆碱间的重量比例为1：1至1：6時，组合物的有效剂量為187至680毫克/公斤体重/天。
其中，红景天萃取物：甘油磷酸胆碱间的重量比例范围为1：3。
其中，红景天萃取物：甘油磷酸胆碱间的重量比例为1：3時，组合物的有效剂量為384毫克/公斤体重/天。
其中，组合物还包括一白藜芦醇。
其中，组合物还包括一瓜拿纳。
其中，组合物呈胶囊形式。
其中，组合物呈粉末状、颗粒状或液体状。
并且，本发明的另一项实施例提供一种上述组合物用于制备治疗肥胖的药物的用途。
因此，通过诱导肥胖及老化实验证实，红景天萃取物与甘油磷酸胆碱能有效降低动物的体重以及体脂肪，甚至还可提升动物体内的抗氧化作用，进而达到有效减肥及延缓老化的目的。
附图说明
图1为本发明于每组受试者的皮肤组织进行毛囊与皮下脂肪染色的影像图。
图2为本发明于每组受试者的皮肤组织进行免疫染色的影像图。
具体实施方式
下面结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述。在下面的描述中阐述了很多具体细节以便于充分理解本发 明，但是本发明还可以采用其他不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似推广，因此本发明不受下面公开的具体实施例的限制。
本发明提供一种具有抑制脂肪形成及抗氧化活性的组合物，该组合物包括有效剂量的一红景天萃取物及一甘油磷酸胆碱及其医药可接受载剂或医药可接受盐。
红景天，属于多年草木或灌木植物。红景天萃取物含有多量东莨宕碱、山萘酚等具有抗菌消炎成份，而且还具有抗缺氧、抗疲劳、延缓衰老及调节内分泌系统的作用。
甘油磷酸胆碱(alpha-Glycerophosphocholine,alpha-GPC)，是一种小分子营养素。甘油磷酸胆碱主要存在于人体细胞和母乳中，或者可由非转基因大豆中通过去乙酰化技术和特殊离子交换技术萃取获得。经研究证实，甘油磷酸胆碱能帮助组织成长重建、器官的活化、恢复缺乏循环的大脑功能、维护大脑注意力、集中力和记忆力等生理功能。根据目前的临床试验研究显示：甘油磷酸胆碱通过口服方式可提高血液中胆碱与乙酰胆碱的浓度，进而降低可体松(cortison)浓度，达到进一步提高体内人类生长激素(hGH)浓度的目的。
其中，红景天萃取物：甘油磷酸胆碱间的重量比例范围为1：1至1：6，于本发明较佳实施例中，红景天萃取物：甘油磷酸胆碱间的重量比例范围为1：3。
此外，组合物还包括一白藜芦醇及一瓜拿纳。白藜芦醇，广泛存在于桑葚、花生、葡萄等多种植物中，尤其以葡萄含量为高。经研究发现，白藜芦醇具有极佳的抗氧化活性，不但能保护人体不受自由基侵袭，当植物受到环境压力、真菌和细菌感染时，也会产生抗毒素来对抗外界的侵袭。
瓜拿纳，是一种兴奋刺激物质，其可增加精神和肌肉强度的抵抗力、忍耐力，且能够减少运动和物理的疲倦。瓜拿纳中咖啡因和咖啡碱所含的黄嘌呤，能够提供最快速并最稳定的思考。
本发明的组合物可制作成粉末状、颗粒状或液体状，还可经加工处理，进而将本发明的组合物制作成胶囊的形式；特别说明的是，胶囊形式可为动物性胶囊或植物性胶囊。动物性胶囊可由动物胶(gelatin)所制成，而植物性胶囊可由羧甲基纤维素纳(sodium carboxymethyl cellulose)所制成，提供使用者口服食用。
本发明所用的术语“医药可接受盐”包括水溶性及水不溶性盐，可保留组合物的生物学功效及性质。本发明所用的术语“医药可接受载剂”涉及将医药制剂自机体的一器官或一部分运送或转移到机体的另一器官或另一部分的物质、组合物或媒剂，其包括有调味剂、增味剂、防腐剂、抗氧化剂、螯合剂、渗透剂、润滑剂、锭剂佐剂、着色剂、保湿剂、结合剂、及等效载剂。
本发明实施例以动物实验作为验证，以证实本发明的组合物具有抑制脂肪形成及抗氧化活性的功效。
动物实验
(1)动物饲育
实验的一受试者来自国家卫生研究院国家实验动物中心，受试者采用雄性6-8周龄的C57BL/6(B6)60只小鼠，起始体重约20克，以10只受试者为一组。每组受试者分别饲养在22±2℃的动物房中，并以定时器控制光照时间及黑暗时间，其中，光照时间与黑暗时间各为12小时。由于受试者通常于黑暗时段进食，移除饲料的最佳时刻为开始要转明亮时，空腹时间可设定为12±2小时。
(2)饲料喂食
受试者以口服给予高脂饲料，并以注射方式施予D-半乳糖。值得说明的是，高脂饲料为了诱发受试者体重肥胖；注射过量的D-半乳糖，会使受试者的体内产生大量活性氧类，进而破坏体内活性氧类浓度的平衡状态，藉以诱导受试者体内产生过氧化效应。
(3)投药设定
于6-8周龄的受试者依体重随机分成六组，每组10只，每只受试者先于动物房给予高脂饲料以及注射D-半乳糖后，每只受试者再通过口服给予本发明含有红景天萃取物及甘油磷酸胆碱的组合物，进行实验12周，实验期间每周测量且记录体重。本发明所用的术语“给予”是指向个体直接投与组合物或组合物的医药可接受盐，其可于个体的体内形成等效量的活性组合物。
实验各组主要可分为：(1)正常组：自由摄食正常饲料，给予无菌逆渗透水10ml/kg。(2)对照组：自由摄食高脂饲料，颈背部皮下注射方式注射0.3-1.2g/kg bw的D-半乳糖；给予无菌逆渗透水10ml/kg。(3)实验组1：自由摄食高脂饲料，颈背部皮下注射0.3-1.2g/kg bw的D-半乳糖；给予1倍剂量的红景天萃取物，其中，红景天萃取物的含量为88.4毫克/公斤体重/天。(4)实验组2：自由摄食高脂饲料，颈背部皮下注射0.3-1.2g/kg bw的D-半乳糖；给予低剂量的本发明组合物(红景天萃取物：甘油磷酸胆碱＝1：1)，其中，本发明组合物的红景天萃取物与甘油磷酸胆碱组合的有效剂量为187毫克/公斤体重/天(红景天萃取物：甘油磷酸胆碱＝1：1)，依体表面积比，相对人体口服0.91克/天剂量。(5)实验组3：自由摄食高脂饲料，颈背部皮下注射0.3-1.2g/kg bw的D-半乳糖；给予中剂量的本发明组合物(红景天萃取物：甘油磷酸胆碱＝1：3)，其中，本发明组合物的红景天萃取物与甘油磷酸胆碱组合的有效剂量为384.4毫克/公斤体重/天(红景天萃取物：甘油磷酸胆碱＝1：3)，依体表面积比，相对人体口服1.87克/天剂量。(6)实验组4：自由摄食高脂饲料，颈背部皮下注射0.3-1.2g/kg bw的D-半乳糖；给予高剂量的本发明组合物(红景天萃取物：甘油磷酸胆碱＝1：6)，其中，本发明组合物的红景天萃取物与甘油磷酸胆碱组合的有效剂量为680.4毫克/公斤体重/天(红景天萃取物：甘油磷酸胆碱＝1：6)，依体表面积比，相对人体口服3.31克/天剂量。
Figure PCTCN2018099822-appb-000001
Figure PCTCN2018099822-appb-000002
实验动物与人体间试验剂量的换算：本评估方法的人体与实验动物间剂量的换算，原则上根据2005年美国食品药物管理局所公告的实验初期估算方法(Estimating the maximum safe starting dose ininitial clinical trials for therapeutics in adult healthy volunteers)，而以60公斤的成人为基准，使用实验动物进行试验时，有效剂量的换算原则上以人体每日每公斤体重的建议摄取量(/kg bw/day)依等效剂量换算之。
由于动物会随着体重的增加而增加其摄食量，所以上述二项换算的方式，动物每天所获得受试样品的摄取量相差不大，因此都可采用。试验组与对照组饲料必须含近似等量的热量、蛋白质、脂肪、钙质等矿物质或维生素。
动物试验结果换算为人体的建议剂量：综合动物试验的统计结果求得最适有效剂量，如单位为饲料中的％时，则以同％为人类在一天中占总饮食摄取量(500克干重)的％为1倍剂量，例如饲料中含1％受试产品组获得最佳综合结果时，视同人类亦摄取1％(5克)为最佳的1倍剂量。如实验是采用每公斤体重(/kg b.w.)为单位时，则一律乘上60kg作为成人的1倍有效剂量。
(4)采样分析
(A)体重变化：
实验期间每周至少要精秤体重1次(宜固定于每天动物室灯光要转暗，并给予饲料前)，并观察每组受试者的体重变化。体重变化换算方式为：体重改变量(weight change)＝结束体重–起始体重。
表1.每组受试者的体重变化
Figure PCTCN2018099822-appb-000003
*P<0.05,**P<0.01,***P<0.001
请参阅表1所示，其为本实施例的各组受试者的体重变化表。由表1结果显示，随着实验周数增加，所有实验的受试者平均体重皆稳定上升，其中，又以对照组的平均体重增加最为明显；然而，对于实验组2～4来说，受试者 经给予本发明的组合物后，其平均体重相较于对照组有显然降低，其中，还以实验组3而言，其受试者的平均体重相比于对照组具有明显降低约7公克的效果；显而得知，本发明通过红景天萃取物与甘油磷酸胆碱的混合喂食，能有效降低受试者体重，而且，又以给予红景天萃取物：甘油磷酸胆碱＝1：3的实验组3，其整体的减重效果为最佳。
(B)脏器与体脂肪重量变化：
动物牺牲时，小心取出腹膜腔内的副睾脂肪、肾脏周围脂肪及肠脂肪进行精秤重量，并计算体脂肪率。体脂肪率计算公式如下：
体脂肪率＝[体脂肪量(g)/体重(g)]×100％。于实际计算时，体脂肪量(g)＝副睾脂肪(g)+肾脏周围脂肪(g)+肠系膜脂肪(g)。体脂肪量的测定尽量由同一人以同方法处理所有的动物，以降低动物个体间的误差。
表2.每组受试者的脏器与体脂肪重量变化
Figure PCTCN2018099822-appb-000004
Figure PCTCN2018099822-appb-000005
*P<0.05,**P<0.01,***P<0.001
请配合参阅表2所示，其为本实施例的各组受试者的脏器与体脂肪重量变化表。由表2结果显示，实验经过12周后，所有实验受试者的体脂肪率及脂肪总量皆有上升趋势，其中，又以对照组上升最为明显(P<0.05)；然而，相较于实验组2～4来说，受试者经给予本发明的组合物后，其体脂肪率及脂肪总量相较于对照组有显然降低(P<0.05)；也就是说，本发明的组成物能有效抑制肥胖与脂肪累积的效果。
(C)血液中各项生化数值变化：
利用血液生化分析体内不易形成体脂肪功能的各项生化数值。其生化分析项目如下：
(a).血脂质：每组受试者禁食12小时后，以异氟醚(isofurane)进行麻醉，收集腹腔动脉的血液，并将其离心收集血清，后续通过血清生化仪分析检测血清中三酸甘油酯、胆固醇、低密度脂蛋白、高密度脂蛋白的浓度。
(b).肝脏脂质：腹腔动脉采血结束后，以生理食盐水冲洗腹腔，再通过氯仿-甲醇萃取法进一步萃取体内脂质，并测量肝脏三酸甘油酯与胆固醇的浓度。
(c).血糖：腹腔动脉采血结束后，利用酵素法及比色原理测量血清中血糖浓度。
(d).肾功能：腹腔动脉采血结束后，利用酵素法及比色原理测量血清中肌酸酐的浓度。
表3.每组受试者的血液生化值变化
Figure PCTCN2018099822-appb-000006
Figure PCTCN2018099822-appb-000007
请配合参阅表3所示，其为本实施例的各组受试者的血液生化值变化表。如上述表3所示，实验经过12周后，血糖结果显示，对照组的血糖浓度相较于正常组有显著性增加(P<0.05)；然而，实验组1～4的血糖浓度比对对照组些微降低。胆固醇结果显示，实验组1～4血清中的胆固醇浓度比对对照组有显著性的降低(P<0.05)。肌酸酐(Creatinine)结果显示，实验组1～3血清中的肌酸酐浓度比对对照组有略微降低趋势，其中，实验组4的肌酸酐浓度显著地低于对照组(P<0.05)。低密度脂蛋白(LDL)结果显示，实验组1～4中低密度脂蛋白浓度比对对照组有显著性地降低(P<0.05)。高密度脂蛋白(HDL)结果显示，实验组1～4中高密度脂蛋白浓度比对对照组有显著性地增高(P<0.05)。因此，通过表3的经实验结果显示，本发明的组成物能够有效抑制形成体脂肪的多项生化活性，有效达到降低体脂率的效果。
(D)血液抗氧化指标变化：
利用酵素法及比色原理测量血清中超氧化物歧化酵素(SOD)、麸胱甘肽过氧化酵素(GSHPx)浓度含量及G6PD(Glucose-6-phosphate dehydrogenase)的 活性浓度。
表4.每组受试者的血液抗氧化指标变化
Figure PCTCN2018099822-appb-000008
*P<0.05,**P<0.01,***P<0.001
请配合参阅表4所示，其为本实施例的每组受试者的血液抗氧化指标变化表。由上述表4所示，实验经过12周后，超氧化物歧化酵素(SOD)、麸胱甘肽过氧化酵素(GSH Px)及G6PD的结果显示，实验组2～4比对对照组有显著性的增加(P<0.05)，其中，又以实验组3的红景天萃取物：甘油磷酸胆碱＝1：3的实施例中，超氧化物歧化酵素(SOD)、麸胱甘肽过氧化酵素(GSH Px)及G6PD测得浓度含量为最高。显而得知，本发明通过给予红景天萃取物与甘油磷酸胆碱，能有效提升抗氧化力的效果，进而达到清除体内过氧化分子与自由基的目的，经实验证实，实验组3的抗氧化效果为最好，进而有助于延缓衰老的效果。
(E)血液中生长贺尔蒙变化：
人类生长激素(human growth hormone，hGH)分析：以human growth hormone ELISA kit分析血清中hGH浓度。
表5.每组受试者的生长贺尔蒙变化
Figure PCTCN2018099822-appb-000009
请配合参阅表5所示，其为本实施例的每组受试者的生长激素变化表。 由上述表5所示，实验经过12周后，于血液中生长激素的结果显示，对照组血清中的生长激素浓度相对正常组有显著性降低(P<0.05)，但实验组1～4比对对照组有显著性的增加(P<0.05)。进一步说明，受试者在经过老化与肥胖的诱导下，通过给予红景天萃取物与甘油磷酸胆碱，还还相对提升体内生长贺尔蒙的作用，达到有助于受试者减肥的效果。
(F)组织切片染色观察
(1).每组受试者以D-半乳糖诱导老化后，需观察毛色变化情形，如果有老化情形，毛发会变白色，因此需要拍照记录。请配合图参阅图1所示，其为本实施例的每组受试者的皮肤组织进行毛囊与皮下脂肪染色的影像图。如图1所示，对照组的毛囊组织相较于正常组来说，有明显发生松散情况，且对照组的皮下脂肪厚度也显著高于正常组；然而，经过试验后的实验组1～4发现，实验组1～4的毛囊组织相较于对照组来说，有逐渐复原成缜密状态，而且其皮下脂肪厚度比例也产生显著性地降低情形。
表6.每组受试者的皮下脂肪厚度变化
Figure PCTCN2018099822-appb-000010
请配合图1及上述表6结果所示，更进一步地发现，实验组2～4通过给予红景天萃取物与甘油磷酸胆碱的受试者，相比于实验组1给予单一红景天萃取物的受试者来说，实验组2～4的组织切片测得的皮下脂肪厚度更有明显降低皮下脂肪的效果，其中，又以实验组3测得皮下脂肪厚度的降低效果为最佳。据以说明，受试者经给予红景天萃取物与甘油磷酸胆碱的组合，除了能有效增加皮肤的毛囊组织，以提升毛发含量的效果之外，还能进一步达到降低体内皮下脂肪厚度的目的。
(2).采集各组受试者的皮肤，并浸泡于10％福尔马林溶液中固定后，以进行4-HNE(4-hydroxynonenal)染色实验；特别说明的是，受试者经注射D- 半乳糖而诱导体内发生脂质过氧化现象，而脂质过氧化过程会产生丙二醛(Malonaldehyde,MDA)和4-羟基壬烯酸(4-hydroxynonenal,HNE)，进而导致细胞膜的流动性和通透性以及细胞结构和功能的改变；是以，本发明可通过4-HNE染色实验，观察各组受试者体内过氧化状态，其中，4-HNE染色测得的沉积量颜色越深时，代表受试者体内过氧化物含量越高；换言之，4-HNE染色测得的沉积量颜色越浅时，代表受试者体内过氧化物含量越低。请配合图参阅图2所示，其为本实施例的每组受试者的皮肤组织进行免疫染色的影像图。
如图2所示，对照组的4-HNE染色实验相较于对正常组来说，其沉积量颜色有显著较深的现象，也就是说，对照组的受试者的体内组织发生严重过氧化现象；然而，经过试验后的实验组2～4而言，其经4-HNE染色的沉积量颜色相较于对照组来说，沉积量颜色有明显较浅的趋势，又以实验组3测得4-HNE染色的沉积量颜色又为更浅，而且沉积量的染色面积更小，进而说明实验组3的抗过氧化的效果为最佳；因此，表示本发明的红景天萃取物与甘油磷酸胆碱的组合，还能进一步达到提升抗过氧化作用的效果及目的。
综上所述，本发明经过实验证实，红景天萃取物与甘油磷酸胆碱的组合，除了能有效降低受试者的体重以及体脂肪之外，甚至还可提升体内抗过氧化作用的效果，其中，又以红景天萃取物与甘油磷酸胆碱的组合配比为1：3时，抑制体脂肪、降低体重及抗氧化作用的效果为最佳；因此，本发明的组合物能够作为制备治疗肥胖的药物，还可提升体内组织抗过氧化作用而实现延缓老化的效果。
显然，所描述的实施例仅仅是本发明的一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。

Claims (10)

  1. 一种具有抑制脂肪形成及抗氧化活性的组合物，其特征在于，该组合物包括有效剂量的红景天萃取物及甘油磷酸胆碱及其医药可接受载剂或医药可接受盐。
  2. 如权利要求1所述的具有抑制脂肪形成及抗氧化活性的组合物，其特征在于，该红景天萃取物：该甘油磷酸胆碱间的重量比例范围为1：1至1：6。
  3. 如权利要求2所述的具有抑制脂肪形成及抗氧化活性的组合物，其中，该红景天萃取物：该甘油磷酸胆碱间的重量比例为1：1至1：6時，该组合物的有效剂量為187至680毫克/公斤体重/天。
  4. 如权利要求2所述的具有抑制脂肪形成及抗氧化活性的组合物，其特征在于，该红景天萃取物：该甘油磷酸胆碱间的重量比例为1：3。
  5. 如权利要求4所述的具有抑制脂肪形成及抗氧化活性的组合物，其特征在于，该红景天萃取物：该甘油磷酸胆碱间的重量比例为1：3時，该组合物的有效剂量為384毫克/公斤体重/天。
  6. 如权利要求1所述的具有抑制脂肪形成及抗氧化活性的组合物，其特征在于，该组合物还包括白藜芦醇。
  7. 如权利要求6所述的具有抑制脂肪形成及抗氧化活性的组合物，其特征在于，该组合物还包括瓜拿纳。
  8. 如权利要求7所述的具有抑制脂肪形成及抗氧化活性的组合物，其特征在于，该组合物呈胶囊形式。
  9. 如权利要求1所述的具有抑制脂肪形成及抗氧化活性的组合物，其特征在于，该组合物呈粉末状、颗粒状或液体状。
  10. 一种如权利要求1所述的组合物用于制备治疗肥胖的药物的用途。
PCT/CN2018/099822 2018-08-10 2018-08-10 具有抑制脂肪形成及抗氧化活性的组合物及其用途 WO2020029221A1 (zh)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1568728A (zh) * 2003-07-17 2005-01-26 林荣坤 一种藏茶及其制备方法
CN101056656A (zh) * 2004-09-15 2007-10-17 哈佛大学校长及研究员协会 在治疗肥胖症和糖尿病中降低er应力
CN101095665A (zh) * 2006-06-27 2008-01-02 中国科学院上海生命科学研究院 Sirt1在预防、控制或治疗肥胖中的用途
CN104413204A (zh) * 2013-08-28 2015-03-18 青岛医防消毒专业技术中心 红景天养颜茶及其制备方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1568728A (zh) * 2003-07-17 2005-01-26 林荣坤 一种藏茶及其制备方法
CN101056656A (zh) * 2004-09-15 2007-10-17 哈佛大学校长及研究员协会 在治疗肥胖症和糖尿病中降低er应力
CN101095665A (zh) * 2006-06-27 2008-01-02 中国科学院上海生命科学研究院 Sirt1在预防、控制或治疗肥胖中的用途
CN104413204A (zh) * 2013-08-28 2015-03-18 青岛医防消毒专业技术中心 红景天养颜茶及其制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MA LI ET AL.: "The effect of salidroside on the sugar and fat metabolism of fatigued mice", THE COMPILATION OF THE 12TH NATIOANL CLINICAL NUTRITION SYMPOSIUM OF CHINESE NUTRITION SOCIETY, 1 October 2009 (2009-10-01) *
WANG MIQU ET AL.: "Discuss on the chills and fever nutrition and health care of vegetables and fruits", MODERN JOURNAL OF INTEGRATED TRADITIONAL CHINESE AND WESTERN MEDICINE, vol. 14, no. 10, 31 May 2005 (2005-05-31), pages 1255 - 1256 *

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