CN104740138A - Composition containing aloe, probiotics and prebiotics and application of composition - Google Patents
Composition containing aloe, probiotics and prebiotics and application of composition Download PDFInfo
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Abstract
Description
技术领域 technical field
本发明涉及组合物及其用途,具体地,涉及芦荟组合物及其在制备药物和食品中的用途、药物和食品。 The present invention relates to a composition and its use, in particular to an aloe composition and its use in preparing medicine and food, medicine and food. the
背景技术 Background technique
据研究报道,人体细胞90%不是人自己的细胞,而是微生物的,人类与其体内共生的微生物共同组成一个“超级生物体”。因此可以说人体有两套基因组,一套是自己的,一套是微生物的。肠道菌群成分、结构和比例与人体健康和疾病发生有着密切关系。不同的肠道菌群谱可以致病,亦可以防病;可以致肥胖,也可引起消瘦;可以诱发糖尿病,也可以预防糖尿病。不同的菌群谱,产生不同的生理和病理效应。它们既是健康和疾病的诱发或始发因素;亦是健康和疾病的“晴雨计”。目前,研究证实人体的多种疾病如糖尿病、高血压、高血脂、癌症等都与肠道菌群密切相关。 According to research reports, 90% of human cells are not human cells, but microorganisms. Humans and their symbiotic microorganisms together form a "super organism". Therefore, it can be said that the human body has two sets of genomes, one is its own and the other is that of microorganisms. The composition, structure and proportion of intestinal flora are closely related to human health and disease occurrence. Different gut flora profiles can cause or prevent disease; can cause obesity or cause emaciation; can induce diabetes or prevent diabetes. Different flora profiles produce different physiological and pathological effects. They are not only the inducing or initiating factors of health and disease; they are also the "barometer" of health and disease. At present, studies have confirmed that various human diseases such as diabetes, hypertension, hyperlipidemia, and cancer are closely related to intestinal flora. the
然而,目前调节动物肠道菌群方面的研究仍有待深入。 However, the current research on regulating the intestinal flora of animals still needs to be in-depth. the
发明内容 Contents of the invention
本发明旨在至少解决现有技术中存在的技术问题之一。为此,本发明的一个目的在于提出一种有效调节动物肠道菌群的手段。 The present invention aims to solve at least one of the technical problems existing in the prior art. Therefore, an object of the present invention is to propose a means for effectively regulating the intestinal flora of animals. the
因而,在本发明的一个方面,本发明提供了一种组合物。根据本发明的实施例,该组合物包含芦荟、益生菌和益生元,其中,所述芦荟、益生菌和益生元的质量比例为6:3:1~6:1:3。根据本发明的一些实施例,本发明的组合物能够有效促进动物肠道内双歧杆菌属、乳杆菌属、乳球菌属等有益菌群的增殖,即能够有效调节动物肠道菌群,进而基于肠道菌群的作用,发挥预防或治疗糖尿病的功效。 Thus, in one aspect of the invention, the invention provides a composition. According to an embodiment of the present invention, the composition comprises aloe, probiotics and prebiotics, wherein the mass ratio of the aloe, probiotics and prebiotics is 6:3:1˜6:1:3. According to some embodiments of the present invention, the composition of the present invention can effectively promote the proliferation of beneficial flora such as Bifidobacterium, Lactobacillus, and Lactococcus in the intestinal tract of animals, that is, it can effectively regulate the intestinal flora of animals, and then based on The role of intestinal flora plays a role in the prevention or treatment of diabetes. the
需要说明的是,在本文中所使用的表达方式“调节动物肠道菌群”中的术语“动物”所指的动物种类不受特别限制。根据本发明的实施例,该动物可以为任何具有肠道器官的动物,优选哺乳动物,更优选大鼠、小鼠、人,最优选人。另外,在本文中所使用的表达方式“预防或治疗”主要是指预防或辅助治疗糖尿病。 It should be noted that the species of animals referred to by the term "animal" in the expression "modulating the intestinal flora of an animal" used herein is not particularly limited. According to an embodiment of the present invention, the animal can be any animal with intestinal organs, preferably a mammal, more preferably a rat, a mouse, a human, and most preferably a human. In addition, the expression "prevention or treatment" used herein mainly refers to the prevention or auxiliary treatment of diabetes. the
根据本发明的实施例,芦荟的来源即提供形式不受特别限制,例如可以直接通过市购获得,也可以以各种芦荟制品提供。根据本发明的一些实施例,所述芦荟以选自芦荟粉、芦荟汁、芦荟凝胶、芦荟提取物的至少一种形式提供。 According to the embodiment of the present invention, the source of the aloe, that is, the form of supply is not particularly limited, for example, it can be obtained directly from the market, or it can be provided in various aloe products. According to some embodiments of the present invention, the aloe is provided in at least one form selected from aloe powder, aloe juice, aloe gel, and aloe extract. the
根据本发明的实施例,益生菌的种类不受特别限制,只要能够有效调节动物肠道菌群,本领域技术人员可以根据实际情况灵活选择。根据本发明的一些实施例,所述益生菌为人体内常见的益生菌属,例如但不限于栖粪杆菌属、真杆菌、梭菌属、梭杆菌属、罗斯拜瑞氏菌 属、粪球菌属、双歧杆菌属、丁酸弧菌属、乳杆菌属或乳球菌属。根据本发明的一些具体示例,所述益生菌为选自直肠真杆菌、食葡糖罗斯拜瑞氏菌、肠道罗斯拜瑞氏菌、普氏栖粪杆菌、酪酸梭菌、凝结芽孢杆菌、两岐双岐杆菌、婴儿双岐杆菌、长双岐杆菌、短双岐杆菌、青春双歧杆菌、德氏乳杆菌保加利亚种、嗜酸乳杆菌、嗜热链球菌、干酪乳杆菌干酪亚种、罗伊氏乳杆菌、乳双歧杆菌、干酪乳杆菌、卷曲乳杆菌、德氏乳杆菌保加利亚亚种、发酵乳杆菌、格氏乳杆菌、瑞士乳杆菌、约氏乳杆菌、植物乳杆菌、鼠李糖乳杆菌、唾液乳杆菌、费氏丙酸杆菌谢氏亚种、乳酸乳球菌乳酸亚种、乳酸乳球菌乳脂亚种、乳酸乳球菌双乙酰亚种、肠膜明串珠菌肠膜亚种的至少一种。 According to the embodiments of the present invention, the types of probiotics are not particularly limited, as long as they can effectively regulate the intestinal flora of animals, those skilled in the art can flexibly choose according to the actual situation. According to some embodiments of the present invention, the probiotics are common probiotics in the human body, such as but not limited to Faecalibacterium, Eubacterium, Clostridium, Fusobacterium, Roseborella, and Faecococcus , Bifidobacterium, Butyvibrio, Lactobacillus or Lactococcus. According to some specific examples of the present invention, the probiotics are selected from the group consisting of Eubacterium rectum, Barretella gluconovorans, Barretella enterica, Faecalibacterium prauszii, Clostridium butyricum, Bacillus coagulans, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium adolescentis, Lactobacillus delbrueckii bulgaricus, Lactobacillus acidophilus, Streptococcus thermophilus, Lactobacillus casei subsp. Lactobacillus reuteri, Bifidobacterium lactis, Lactobacillus casei, Lactobacillus crispatus, Lactobacillus delbrueckii subsp, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus plantarum, murine Lactobacillus salivarius, Lactobacillus salivarius, Propionibacterium frescheri subsp. Shermanii, Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris, Lactococcus lactis subsp. diacetyl, Leuconostoc enterococci subsp. at least one of . the
根据本发明的实施例,所述益生元的种类不受特别限制,只要能够有效促进有益菌群的生长即可。根据本发明的一些实施例,所述益生元为选自菊粉、蜂胶、壳寡糖、低聚果糖、低聚半乳糖、低聚木糖的至少一种。由此,可以有效刺激有益菌群的生长。 According to the embodiments of the present invention, the type of the prebiotic is not particularly limited, as long as it can effectively promote the growth of beneficial bacteria. According to some embodiments of the present invention, the prebiotic is at least one selected from inulin, propolis, chitooligosaccharides, fructooligosaccharides, galactooligosaccharides, and xylooligosaccharides. Thereby, the growth of beneficial bacteria can be effectively stimulated. the
在本发明的第二方面,本发明提供了前面所述的组合物在调节动物肠道菌群中的用途。发明人惊奇地发现,本发明的组合物能够显著提高所述动物肠道内的有益菌群数量,调节动物肠道菌群,进而基于肠道菌群的作用,有效降低所述动物的血糖浓度,从而有效预防或治疗糖尿病。 In the second aspect of the present invention, the present invention provides the use of the aforementioned composition in regulating intestinal flora of animals. The inventors have surprisingly found that the composition of the present invention can significantly increase the number of beneficial bacteria in the intestinal tract of the animal, regulate the intestinal flora of the animal, and then effectively reduce the blood sugar concentration of the animal based on the effect of the intestinal flora, Thereby effectively preventing or treating diabetes. the
根据本发明的实施例,服用本发明的组合物没有任何毒副作用,因而所述组合物的给药剂量不受特别限制,本领域技术人员可以根据给药对象的健康状况灵活选择。根据本发明一些实施例,将所述组合物以0.5g芦荟/kg/d的剂量对所述动物进行给药。由此,被给药动物肠道内有益菌群的数量明显增加,即本发明的组合物调节动物肠道菌群的效果显著。 According to the embodiments of the present invention, taking the composition of the present invention does not have any toxic side effects, so the dosage of the composition is not particularly limited, and those skilled in the art can flexibly choose according to the health status of the subject to be administered. According to some embodiments of the present invention, the composition is administered to the animals at a dose of 0.5 g aloe/kg/d. Thus, the number of beneficial bacteria in the intestinal tract of the administered animal is significantly increased, that is, the effect of the composition of the present invention on regulating the intestinal flora of the animal is remarkable. the
需要说明的是,在本文中所使用的术语“给药”应作广义理解,除了常规的药物给药外,针对组合物或食品时可以理解为对动物进行饲喂或提供该食品。 It should be noted that the term "administration" used herein should be understood in a broad sense. In addition to conventional drug administration, it can be understood as feeding or providing the food for the composition or food. the
在本发明的第三方面,本发明提供了前面所述的组合物在制备药物中的用途。根据本发明的实施例,所述药物用于调节动物肠道菌群。 In the third aspect of the present invention, the present invention provides the use of the aforementioned composition in the preparation of medicaments. According to an embodiment of the present invention, the medicament is used for regulating intestinal flora of animals. the
上述药物能够用于调节动物肠道菌群,进而通过肠道菌群的作用能够发挥降血糖的功效。因而,根据本发明的一些实施例,所述药物用于预防或治疗糖尿病。 The above-mentioned drugs can be used to regulate the intestinal flora of animals, and then exert the effect of lowering blood sugar through the action of the intestinal flora. Thus, according to some embodiments of the present invention, the medicament is used for preventing or treating diabetes. the
根据本发明的实施例,所述药物的给药剂量不受特别限制,只要能够有效调节动物肠道菌群即可。根据本发明的一些具体示例,将所述药物以0.5g芦荟/kg/d的剂量对所述动物进行给药。由此,被给药动物肠道内的有益菌群数量显著增加,血糖浓度明显降低。 According to the embodiments of the present invention, the dosage of the drug is not particularly limited, as long as it can effectively regulate the animal intestinal flora. According to some specific examples of the present invention, the drug is administered to the animal at a dose of 0.5 g aloe/kg/d. As a result, the number of beneficial bacteria in the intestinal tract of the administered animals was significantly increased, and the blood sugar concentration was significantly reduced. the
在本发明的第四方面,本发明还提供了一种药物。根据本发明的实施例,所述药物包含:前面所述的组合物;以及药学上可接受的赋形剂。发明人惊奇地发现,本发明的药物能够显著提高被给药动物肠道内双歧杆菌、乳球菌、乳杆菌等益生菌的数量,调节动物的肠道菌群,进而通过肠道菌群的作用有效预防或治疗糖尿病。 In the fourth aspect of the present invention, the present invention also provides a medicine. According to an embodiment of the present invention, the medicine comprises: the aforementioned composition; and a pharmaceutically acceptable excipient. The inventors have surprisingly found that the drug of the present invention can significantly increase the number of probiotics such as Bifidobacteria, Lactococcus, and Lactobacillus in the intestinal tract of the administered animal, regulate the intestinal flora of the animal, and then through the effect of the intestinal flora Effectively prevent or treat diabetes. the
根据本发明的实施例,赋形剂的种类不受特别限制,只要能够使药物形成容易进行给药的剂型即可。根据本发明的一些具体示例,所述赋形剂为选自粘合剂、填料、涂膜聚合物、增塑剂、助流剂、崩解剂和润滑剂的至少一种。 According to the embodiments of the present invention, the types of excipients are not particularly limited, as long as the drug can be formed into a dosage form that is easy to administer. According to some specific examples of the present invention, the excipient is at least one selected from binders, fillers, coating polymers, plasticizers, glidants, disintegrants and lubricants. the
根据本发明的实施例,本发明的药物的剂型不受特别限制,只要能够便于进行给药即可。 根据本发明的一些具体示例,所述药物呈选自胶囊剂、丸剂、片剂、颗粒剂、口服液体、内服膏剂、气雾剂以及喷雾剂的至少一种的形式。根据本发明的一些优选实施例,所述药物呈胶囊剂的形式。由此,易于进行给药。 According to the embodiments of the present invention, the dosage form of the medicament of the present invention is not particularly limited, as long as it can be administered conveniently. According to some specific examples of the present invention, the drug is in the form of at least one selected from capsules, pills, tablets, granules, oral liquids, internal ointments, aerosols and sprays. According to some preferred embodiments of the present invention, the medicament is in the form of capsules. Thus, administration is facilitated. the
根据本发明的实施例,所述药物用于调节动物肠道菌群。进而,通过肠道菌群的作用能够发挥降血糖的功效。因而,根据本发明的另一些实施例,所述药物用于预防或治疗糖尿病。 According to an embodiment of the present invention, the medicament is used for regulating intestinal flora of animals. Furthermore, the effect of lowering blood sugar can be exerted through the action of intestinal flora. Therefore, according to other embodiments of the present invention, the medicament is used for preventing or treating diabetes. the
根据本发明的实施例,本发明的药物的给药剂量不受特别限制,实际应用中,可以根据给药对象的健康状况灵活选择。根据本发明的一些实施例,所述药物的给药剂量为0.5g芦荟/kg/d。由此,被给药动物肠道内双歧杆菌、乳杆菌、乳球菌等益生菌的数量显著增加,调节动物肠道菌群的效果显著,进而基于肠道菌群的作用,能够有效降低被给药动物的血糖浓度,从而预防或治疗糖尿病。 According to the embodiments of the present invention, the dosage of the drug of the present invention is not particularly limited, and in practical applications, it can be flexibly selected according to the health status of the subject to be administered. According to some embodiments of the present invention, the dosage of the drug is 0.5g aloe/kg/d. As a result, the number of probiotics such as Bifidobacterium, Lactobacillus, and Lactococcus in the intestines of the animals being administered significantly increased, and the effect of regulating the intestinal flora of the animals was remarkable. Furthermore, based on the effect of the intestinal flora, it could effectively reduce the Blood sugar concentration of drug animals, thereby preventing or treating diabetes. the
在本发明的第五方面,本发明还提供了一种食品。根据本发明的实施例,所述食品包含前面所述的组合物;以及食品学上可接受的添加剂。发明人发现,本发明的食品能够显著提高被给药动物肠道内双歧杆菌、瘤胃球菌等益生菌的数量,有效调节动物的肠道菌群,进而通过肠道菌群的作用有效预防或治疗糖尿病。 In the fifth aspect of the present invention, the present invention also provides a food. According to an embodiment of the present invention, the food comprises the aforementioned composition; and food acceptable additives. The inventors found that the food of the present invention can significantly increase the number of probiotics such as Bifidobacterium and Ruminococcus in the intestinal tract of the animal being administered, effectively regulate the intestinal flora of the animal, and then effectively prevent or treat diabetes. the
需要说明的是,在本文中所使用的术语“食品”应作广义理解,其可以是任何可被食用的形式,即除了常规的食品形式外,本发明的食品还可以为保健品、饮品等。 It should be noted that the term "food" used herein should be understood in a broad sense, and it can be in any edible form, that is, in addition to conventional food forms, the food of the present invention can also be health care products, drinks, etc. . the
在本发明的第六方面,本发明还提供了前面所述的药物或食品在调节动物肠道菌群中的用途。根据本发明的实施例,对动物给药前面所述的本发明的药物或食品,能够显著提高被给药动物肠道内双歧杆菌、乳球菌、乳杆菌等益生菌的数量,有效调节动物的肠道菌群,进而通过肠道菌群的作用有效预防或治疗糖尿病。 In the sixth aspect of the present invention, the present invention also provides the use of the aforementioned medicine or food in regulating the intestinal flora of animals. According to the embodiments of the present invention, administering the above-mentioned medicine or food of the present invention to animals can significantly increase the number of probiotics such as Bifidobacterium, Lactococcus, and Lactobacillus in the intestinal tract of the animal being administered, and effectively regulate the animal's health. Intestinal flora, and then effectively prevent or treat diabetes through the role of intestinal flora. the
根据本发明的第七方面,本发明还提供了一种调节动物肠道菌群的方法。根据本发明的实施例,该方法是对所述动物给药前面所述本发明的组合物、药物或者食品。根据本发明的实施例,利用本发明的方法能够显著提高被给药动物肠道内双歧杆菌、乳球菌、乳杆菌等益生菌的数量,有效调节动物的肠道菌群,进而通过肠道菌群的作用有效预防或治疗糖尿病。 According to the seventh aspect of the present invention, the present invention also provides a method for regulating intestinal flora of animals. According to an embodiment of the present invention, the method is to administer the aforementioned composition, drug or food of the present invention to the animal. According to the embodiments of the present invention, using the method of the present invention can significantly increase the number of probiotics such as Bifidobacterium, Lactococcus, and Lactobacillus in the intestinal tract of the administered animal, effectively regulate the intestinal flora of the animal, and then pass the intestinal bacteria The role of the group is effective in preventing or treating diabetes. the
此外,根据本发明的实施例,所述组合物以及包含该组合物的本发明的食品或药物,调节动物肠道菌群的作用优于单一成分的芦荟、益生菌或益生元的作用效果。 In addition, according to the embodiments of the present invention, the composition and the food or medicine of the present invention containing the composition can regulate the intestinal flora of animals better than the effect of aloe vera, probiotics or prebiotics as a single component. the
还需要说明的是,本发明的组合物、药物、食品及其在调节动物肠道菌群中的用途,正是本发明的发明人经过艰苦的创造性劳动和大量的实验工作才意外发现的。 It should also be noted that the composition, medicine, food and their use in regulating animal intestinal flora of the present invention were unexpectedly discovered by the inventors of the present invention through hard creative work and a lot of experimental work. the
本发明至少具有以下优点之一: The present invention has at least one of the following advantages:
1、本发明的组合物,所有原料取于自然、源于天然,且不含任何化学制剂,无毒副作用、安全可靠;原料来源广泛易得,组方配伍科学合理,疗效确切,具有协同增效作用;且制备工艺简单,贮运和应用安全,生产成本低廉,易被消费者接受; 1. In the composition of the present invention, all raw materials are taken from nature, are derived from nature, and do not contain any chemical preparations, have no toxic and side effects, are safe and reliable; the sources of raw materials are widely and easily available, the prescription compatibility is scientific and reasonable, the curative effect is definite, and it has synergistic enhancement. efficacy; and the preparation process is simple, safe in storage, transportation and application, low in production cost, and easily accepted by consumers;
2、本发明的组合物、药物及食品,经过动物功能试验和人群食用试验都证明无任何毒副作用,可使病人空腹血糖显著下降,有显著的降血糖作用,符合保健品的要求和发展趋势,适于高血糖、肥胖人群以及老年人群等,通过日常服用,从治本的角度出发,通过调节肠道菌群、起到降血糖的作用,最终达到保护健康的目的。 2. The composition, medicine and food of the present invention have been proved to have no toxic side effects through animal function tests and human consumption tests, can significantly reduce the fasting blood sugar of patients, have a significant hypoglycemic effect, and meet the requirements and development trends of health care products , suitable for people with high blood sugar, obesity and the elderly, through daily consumption, from the perspective of treating the root cause, by regulating intestinal flora, lowering blood sugar, and finally achieving the purpose of protecting health. the
3、本发明通过对纯天然原料的合理组配,实现了便捷的、显著的降血糖等保健功效,药效明显、安全性好,质量稳定,产品可长期保存,为人们日常保健提供了新的选择。 3. Through the reasonable combination of pure natural raw materials, the present invention realizes convenient and significant health effects such as hypoglycemia, obvious drug effect, good safety, stable quality, long-term preservation of the product, and provides a new way for people's daily health care. s Choice. the
本发明的附加方面和优点将在下面的描述中部分给出,部分将从下面的描述中变得明显,或通过本发明的实践了解到。 Additional aspects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. the
具体实施方式 Detailed ways
下面详细描述本发明的实施例。下面描述的实施例是示例性的,仅用于解释本发明,而不能理解为对本发明的限制。实施例中未注明具体技术或条件的,按照本领域内的文献所描述的技术或条件或者按照产品说明书进行。所用试剂或仪器未注明生产厂商者,均为可以通过市购获得的常规产品。 Embodiments of the present invention are described in detail below. The embodiments described below are exemplary only for explaining the present invention and should not be construed as limiting the present invention. If no specific technique or condition is indicated in the examples, it shall be carried out according to the technique or condition described in the literature in this field or according to the product specification. The reagents or instruments used were not indicated by the manufacturer, and they were all commercially available conventional products. the
实施例1 Example 1
按照表1所示的配方,按照下述工艺制备组合物。 According to the formula shown in Table 1, the composition was prepared according to the following process. the
表1本发明的组合物配方(原料的重量单位:份) Table 1 Composition formula of the present invention (weight unit of raw material: part)
具体操作步骤如下: The specific operation steps are as follows:
1、芦荟粉 1. Aloe vera powder
本发明采用的芦荟粉,可来源于市场,也可自行制备,制备方法为常用方法。 The aloe vera powder that the present invention adopts can be derived from the market, and can also be prepared by itself, and the preparation method is a common method. the
2、芦荟酪酸梭菌蜂胶胶囊 2. Aloe Vera Clostridium Butyricum Propolis Capsules
酪酸梭菌菌种经液体培养,收集和洗涤菌体,干燥制备成活性菌粉,按照6/3/1的比例把芦荟粉、酪酸梭菌菌粉和蜂胶搅拌均匀,然后用0号胶囊包装,得到芦荟酪酸梭菌蜂胶胶囊,其中,酪酸梭菌活菌数不低于1.0×108CFU/g。 Clostridium butyricum strains are cultivated in liquid, collected and washed, and dried to prepare active bacterial powder. Mix aloe vera powder, Clostridium butyricum powder and propolis evenly according to the ratio of 6/3/1, and then pack it in No. 0 capsules to obtain aloe Clostridium butyricum propolis capsules, wherein the number of live bacteria of Clostridium butyricum is not less than 1.0×10 8 CFU/g.
3、芦荟双歧杆菌菊粉胶囊 3. Aloe Bifidobacteria Inulin Capsules
双歧杆菌菌种经液体培养,收集和洗涤菌体,干燥制备成活性菌粉,按照3/1/1的比例把芦荟粉、双歧杆菌菌粉和菊粉搅拌均匀,然后用0号胶囊包装,得到芦荟双歧杆菌菊粉胶囊,其中,双歧杆菌活菌数不低于1.0×108CFU/g。 Bifidobacteria strains are cultured in liquid, collected and washed, dried to prepare active bacteria powder, mix aloe vera powder, bifidobacteria powder and inulin according to the ratio of 3/1/1, and then use No. 0 capsule Packing to obtain bifidobacterium aloe inulin capsules, wherein the number of viable bifidobacteria is not less than 1.0×10 8 CFU/g.
4、芦荟植物乳杆菌壳寡糖胶囊 4. Aloe plant Lactobacillus chitosan oligosaccharide capsules
植物乳杆菌菌种经液体培养,收集和洗涤菌体,干燥制备成活性菌粉,按照6/3/1的比例把芦荟粉、植物乳杆菌菌粉和壳寡糖搅拌均匀,然后用0号胶囊包装,得到芦荟植物乳杆菌壳寡糖胶囊,其中,植物乳杆菌活菌数不低于1.0×108CFU/g。 Lactobacillus plantarum strains are cultured in liquid, collected and washed, and dried to prepare active bacterial powder. Stir aloe powder, Lactobacillus plantarum powder and chitosan oligosaccharide evenly according to the ratio of 6/3/1, and then use No. 0 Packing in capsules to obtain Lactobacillus plantarum chitosan oligosaccharide capsules, wherein the viable count of Lactobacillus plantarum is not less than 1.0×10 8 CFU/g.
5、芦荟肠道罗斯拜瑞氏菌低聚果糖胶囊 5. Aloe Vera Intestinal Rosie Bacillus Fructose Oligosaccharide Capsules
肠道罗斯拜瑞氏菌菌种经液体培养,收集和洗涤菌体,干燥制备成活性菌粉,按照6/3/1的比例把芦荟粉、肠道罗斯拜瑞氏菌菌粉和低聚果糖搅拌均匀,然后用0号胶囊包装,得到芦荟肠道罗斯拜瑞氏菌低聚果糖胶囊,其中,肠道罗斯拜瑞氏菌活菌数不低于1.0×108CFU/g。 Enterobacteriaceae Roseria species are cultivated in liquid, collected and washed, and dried to prepare active bacterial powder. According to the ratio of 6/3/1, aloe vera powder, enterica Roseriabacteria powder and oligomerization Stir the fructose evenly, and then pack it in No. 0 capsules to obtain fructo-oligosaccharide capsules of B. enterica Ros. B. fructooligosaccharides, wherein the number of viable bacteria of B. enterica Ros. B. is not less than 1.0×10 8 CFU/g.
6、芦荟嗜酸乳杆菌低聚半乳糖胶囊 6. Aloe Lactobacillus acidophilus galactooligosaccharide capsules
嗜酸乳杆菌菌种经液体培养,收集和洗涤菌体,干燥制备成活性菌粉,按照12/5/3的比例把芦荟粉、嗜酸乳杆菌菌粉和低聚半乳糖搅拌均匀,然后用0号胶囊包装,得到芦荟嗜酸乳杆菌低聚半乳糖胶囊,其中,嗜酸乳杆菌活菌数不低于1.0×108CFU/g。 Lactobacillus acidophilus strains are cultured in liquid, collected and washed, and dried to prepare active bacteria powder. Stir aloe vera powder, Lactobacillus acidophilus powder and galactooligosaccharide evenly according to the ratio of 12/5/3, and then Packaged in No. 0 capsules to obtain Lactobacillus aloe acidophilus galacto-oligosaccharide capsules, wherein the viable count of Lactobacillus acidophilus is not less than 1.0×10 8 CFU/g.
7、芦荟发酵乳杆菌低聚木糖胶囊 7. Aloe fermented Lactobacillus xylooligosaccharide capsules
发酵乳杆菌菌种经液体培养,收集和洗涤菌体,干燥制备成活性菌粉,按照12/3/5的比例把芦荟粉、发酵乳杆菌菌粉和低聚木糖搅拌均匀,然后用0号胶囊包装,得到芦荟发酵乳杆菌低聚木糖胶囊,其中,发酵乳杆菌活菌数不低于1.0×108CFU/g。 The strains of Lactobacillus fermentum are cultured in liquid, collected and washed, and dried to prepare active bacterial powder. Stir the aloe vera powder, Lactobacillus fermentum powder and xylo-oligosaccharide evenly according to the ratio of 12/3/5, and then use 0 packed in capsules to obtain xylooligosaccharide capsules of Lactobacillus fermentum, wherein the number of viable Lactobacillus fermentum is not less than 1.0×10 8 CFU/g.
8、芦荟凝结芽孢杆菌低聚果糖胶囊 8. Aloe Bacillus coagulans fructooligosaccharide capsules
凝结芽孢杆菌菌种经液体培养,收集和洗涤菌体,干燥制备成活性菌粉,按照6/3/1的比例把芦荟粉、凝结芽孢杆菌菌粉和低聚果糖搅拌均匀,然后用0号胶囊包装,得到芦荟凝结芽孢杆菌低聚果糖胶囊,其中,凝结芽孢杆菌活菌数不低于1.0×108CFU/g。 Bacillus coagulans strains are cultivated in liquid, collected and washed, and dried to prepare active bacteria powder. Stir aloe powder, Bacillus coagulans powder and fructooligosaccharides evenly according to the ratio of 6/3/1, and then use No. 0 Packing in capsules to obtain Bacillus coagulans fructo-oligosaccharide capsules, wherein the number of viable Bacillus coagulans is not less than 1.0×10 8 CFU/g.
9、芦荟嗜热链球菌菊粉胶囊 9. Aloe Streptococcus thermophilus inulin capsules
嗜热链球菌菌种经液体培养,收集和洗涤菌体,干燥制备成活性菌粉,按照6/3/1的比例把芦荟粉、嗜热链球菌菌粉和菊粉搅拌均匀,然后用0号胶囊包装,得到芦荟嗜热链球菌菊粉胶囊,其中,嗜热链球菌活菌数不低于1.0×108CFU/g。 Streptococcus thermophilus strains are cultured in liquid, collected and washed, and dried to prepare active bacteria powder. Stir aloe powder, Streptococcus thermophilus bacteria powder and inulin evenly according to the ratio of 6/3/1, and then use 0 No. capsules are packaged to obtain Aloe Streptococcus thermophilus inulin capsules, wherein the number of viable Streptococcus thermophilus is not less than 1.0×10 8 CFU/g.
10、芦荟罗伊氏乳杆菌壳寡糖胶囊 10. Aloe Lactobacillus reuteri Chitooligosaccharide Capsules
罗伊氏乳杆菌菌种经液体培养,收集和洗涤菌体,干燥制备成活性菌粉,按照6/3/1的比例把芦荟粉、罗伊氏乳杆菌菌粉和壳寡糖搅拌均匀,然后用0号胶囊包装,得到芦荟罗伊 氏乳杆菌壳寡糖胶囊,其中,罗伊氏乳杆菌活菌数不低于1.0×108CFU/g。 Lactobacillus reuteri strains are cultured in liquid, collected and washed, and dried to prepare active bacterial powder. Stir aloe vera powder, Lactobacillus reuteri bacterial powder and chitosan oligosaccharide evenly according to the ratio of 6/3/1. Then pack it in No. 0 capsules to obtain Lactobacillus reuteri chitosan oligosaccharide capsules, wherein the number of live bacteria of Lactobacillus reuteri is not less than 1.0×10 8 CFU/g.
11、芦荟植物乳杆菌菊粉压片糖果 11. Aloe Lactobacillus Plantarum Inulin Tablet Candy
将芦荟粉、植物乳杆菌粉、菊粉经80目筛滤,配料比例6:3:1,混和搅拌时间15分钟。干燥时温度为60℃,颗粒水分为0.5%,压片成型时控制环境湿度,相对湿度为60%。 Filter the aloe vera powder, Lactobacillus plantarum powder, and inulin through an 80-mesh sieve, the proportion of ingredients is 6:3:1, and the mixing time is 15 minutes. The temperature during drying is 60°C, the moisture content of the granules is 0.5%, and the ambient humidity is controlled during tablet molding, and the relative humidity is 60%. the
实施例2:急性毒性测定 Embodiment 2: determination of acute toxicity
利用6周龄无特殊病原体(SPF)SD大鼠进行急性毒性试验,具体操作如下: Use 6-week-old special pathogen-free (SPF) SD rats to conduct acute toxicity test, the specific operation is as follows:
将实施例1中制备得到的各组合物悬浮于0.5%的甲基纤维素溶液中,分别以1g/kg、5g/kg和10g/kg的剂量一次口服施用于每组的5只SD大鼠,观察大鼠的死亡、临床症状以及体重变化,并进行血液试验和血液生化试验,在尸检时,肉眼检查胸腹部胃肠组织的任何异常现象。 Each composition prepared in Example 1 was suspended in 0.5% methylcellulose solution, and was orally administered to 5 SD rats in each group at a dose of 1 g/kg, 5 g/kg and 10 g/kg respectively , observe the death, clinical symptoms and body weight changes of the rats, and conduct blood tests and blood biochemical tests. At the time of autopsy, any abnormalities in the gastrointestinal tissues of the chest and abdomen were visually inspected. the
实验结果:本发明的各组合物未引起任何特定的临床症状、体重变化或死亡,血液试验、血液生化试验和尸检也没有变化。因此,由于直至10g/kg的剂量不会引起大鼠的任何中毒变化,可判断其半数致死量(LD50)远远大于10g/kg,本发明涉及的各组合物被评定为安全无毒物质。 Experimental results: each composition of the present invention did not cause any specific clinical symptoms, body weight change or death, and there was no change in blood test, blood biochemical test and autopsy. Therefore, since the dose up to 10g/kg does not cause any toxic changes in rats, it can be judged that its median lethal dose (LD50) is far greater than 10g/kg, and the compositions involved in the present invention are evaluated as safe and non-toxic substances. the
实施例3:调节人肠道菌群功能实验 Example 3: Experiment on regulating the function of human intestinal flora
依据卫生部《保健食品检验与评价技术规范(2003年)》的调节肠道菌群功能人体试食实验评价办法,对实施例1中制备获得的各组合物进行评价,具体操作如下: According to the Ministry of Health's "Health Food Inspection and Evaluation Technical Specifications (2003)", the evaluation method of human body test food experiment for regulating intestinal flora function, each composition prepared in Example 1 is evaluated, and the specific operation is as follows:
1.试食实验分组 1. Grouping of food-testing experiments
试食实验分组情况如表2所示: The grouping situation of the eating experiment is shown in Table 2:
表2试食实验分组表 Table 2 grouping table of eating experiment
2.人体试食实验方法 2. Human food test method
将受试者随机分成12个组,每组20人,在受试者试食之前,均无菌采取受试者粪便,经16SrDNA测序检验肠道菌群,作为本底水平的参照。 The subjects were randomly divided into 12 groups, 20 people in each group. Before the subjects tried to eat, the feces of the subjects were collected aseptically, and the intestinal flora was tested by 16SrDNA sequencing as a reference for the background level. the
按表2的分组情况,组1服用对照组、组2服用组合1,组3服用组合2,组4服用组合3,组5服用组合4,组6服用组合5,组7服用组合6,组8服用组合7,组9服用组合8,组10服用组合9,组11服用组合10,组12服用组合11,4周后,采取受试者粪便,经16SrDNA测序检验肠道菌群,与本底水平对比,对比其相对丰度增加的倍数。 According to the grouping situation in Table 2, group 1 took the control group, group 2 took the combination 1, group 3 took the combination 2, group 4 took the combination 3, group 5 took the combination 4, group 6 took the combination 5, group 7 took the combination 6, and group Group 8 took combination 7, group 9 took combination 8, group 10 took combination 9, group 11 took combination 10, and group 12 took combination 11. After 4 weeks, the feces of the subjects were collected, and the intestinal flora was tested by 16SrDNA sequencing. Compared with the bottom level, compare the multiple of its relative abundance increase. the
3.肠道菌群检测方法 3. Detection method of intestinal flora
粪便样本首先进行DNA提取,PCR扩增16SrDNA的V3~V5区域,然后用454平台测序,测序方向V5->V3。每个样品原始数据平均7795条tag,读长400bp左右。最终用于分析的tag数平均为3235,读长265bp左右。 Stool samples were first extracted from DNA, and the V3-V5 region of 16SrDNA was amplified by PCR, and then sequenced on the 454 platform, and the sequencing direction was V5->V3. The raw data of each sample has an average of 7795 tags, and the read length is about 400bp. The average number of tags used for analysis is 3235, and the read length is about 265bp. the
16S分析主要采用mothur软件(http://www.mothur.org/wiki/Mothur_manual)包括质控,OTU聚类,注释等分析,并在完成数据物种分类的基础上,分析各个物种的相对丰度。 16S analysis mainly uses mothur software (http://www.mothur.org/wiki/Mothur_manual), including quality control, OTU clustering, annotation and other analysis, and on the basis of completing the data species classification, analyze the relative abundance of each species . the
4.实验结果 4. Experimental results
实验结果如下表3所示: The experimental results are shown in Table 3 below:
表3人肠道菌群各菌属的测序数据丰度对比(与本底水平相比提高倍数) Table 3 Comparison of the abundance of sequencing data of each genera of human intestinal flora (increased by multiple compared with the background level)
由表3的数据可知,服用了各组合物的实验组相对于对照组,真杆菌属、栖粪杆菌属、罗斯拜瑞氏菌属、罗斯氏菌属、乳酸菌属等益生菌数均有明显的增加。由此表明,本发明的组合物能够调节动物肠道菌群的效果显著。 As can be seen from the data in Table 3, compared with the control group, the number of probiotics such as Eubacterium, Faecalibacterium, Roseborella, Roseburia, and Lactobacillus in the experimental group that took each composition increased significantly. increase. This shows that the composition of the present invention has a remarkable effect of regulating the intestinal flora of animals. the
实施例4:降血糖动物实验 Embodiment 4: hypoglycemic animal experiment
按照卫生部《保健食品检验与评价技术规范(2003年)》的辅助降血糖功能动物实验评 价办法,对实施例1中制备获得的各组合物进行评价,具体操作如下: According to the animal experiment evaluation method of auxiliary hypoglycemic function of the Ministry of Health "Health Food Inspection and Evaluation Technical Specifications (2003)", each composition prepared in Example 1 is evaluated, and the specific operations are as follows:
1、试验方法 1. Test method
取雄性SD大鼠80只,按照标准方法制备小剂量链佐菌素致糖尿病大鼠模型,三日后根据大鼠血糖值随机分为8组,每组10只。各组连续灌胃给药8天,每日1次,空白组给予等量蒸馏水,最后一次给药后两小时取血,测定血糖值。 Eighty male SD rats were taken, and a low-dose streptozotocin-induced diabetic rat model was prepared according to the standard method. Three days later, the rats were randomly divided into 8 groups according to the blood glucose level, with 10 rats in each group. Each group was administered intragastrically for 8 days, once a day, and the blank group was given the same amount of distilled water. Two hours after the last administration, blood was taken to measure the blood sugar level. the
2、试验对象 2. Test object
空白组:给予蒸馏水; Blank group: given distilled water;
对照1组:给予二甲双胍,给药剂量为300mg/kg; Control group 1: Metformin was administered at a dose of 300 mg/kg;
对照2组:给予芦荟粉,给药剂量为300mg/kg; Control group 2: give aloe vera powder, the dosage is 300mg/kg;
对照3组:给予酪酸梭菌,给药剂量为300mg/kg Control group 3: given Clostridium butyricum, the dosage was 300mg/kg
对照4组:给予蜂胶,给药剂量为300mg/kg Control group 4: give propolis, the dosage is 300mg/kg
对照5组:给予芦荟粉0.5g芦荟/kg/d,酪酸梭菌150mg/kg,其中,酪酸梭菌活菌数不低于1.0×108CFU/g; Control group 5: given aloe vera powder 0.5g aloe vera/kg/d, Clostridium butyricum 150mg/kg, in which the number of live bacteria of Clostridium butyricum was not less than 1.0×10 8 CFU/g;
实验组1:给予本发明的组合1(0.5g芦荟/kg/d,蜂胶80mg/kg,酪酸梭菌150mg/kg,其中,酪酸梭菌活菌数不低于1.0×108CFU/g)。 Experimental group 1: given combination 1 of the present invention (0.5g aloe vera/kg/d, propolis 80mg/kg, Clostridium butyricum 150mg/kg, wherein the number of live bacteria of Clostridium butyricum is not less than 1.0×10 8 CFU/g) .
实验组2:给予本发明的组合2(植物乳杆菌150mg/kg,其中植物乳杆菌活菌数不低于1.0×108CFU/天,菊粉:1.2g/天,0.5g芦荟/kg/d) Experimental group 2: given combination 2 of the present invention (Lactobacillus plantarum 150mg/kg, wherein the number of viable Lactobacillus plantarum is not less than 1.0×10 8 CFU/day, inulin: 1.2g/day, 0.5g aloe/kg/ d)
3、实验结果 3. Experimental results
各组降血糖的结果如表4所示。 The results of hypoglycemia in each group are shown in Table 4. the
表4各组降血糖效果比较 Table 4 Comparison of hypoglycemic effects in each group
注:(1)与空白组比较*P<0.01;(2)与空白组比较ΔP<0.05 Note: (1) *P<0.01 compared with the blank group; (2) Δ P<0.05 compared with the blank group
表4的结果表明,对照1组、对照2组、对照3组、对照4组、对照5组以及实验组1、实验组2对小鼠实验性糖尿病的高血糖均具有下降作用,本发明的组合物、以及二甲双胍对小鼠实验性糖尿病的高血糖具有极其显著的下降作用,结合表2的实验结果,说明本发明的组合物显著增加了益生菌菌群数,而益生菌菌群的增加导致了血糖的降低,显示本发明的组 合物具有降血糖的功能,相对于单一的芦荟粉、益生菌或其组合,本发明的组合物在降低实验小鼠血糖方面的作用效果更佳,说明本发明组合物中的芦荟、益生菌、益生元具有协同增效作用,本发明具有明显的技术优势,具有显著的辅助治疗作用。 The result of table 4 shows, control 1 group, control 2 groups, control 3 groups, control 4 groups, control 5 groups and experimental group 1, experimental group 2 all have descending effect to the hyperglycemia of mice experimental diabetes, the present invention The composition and metformin have a very significant reduction effect on the hyperglycemia of mouse experimental diabetes. In combination with the experimental results in Table 2, it is shown that the composition of the present invention significantly increases the number of probiotic flora, and the increase of probiotic flora Caused the reduction of blood sugar, shows that composition of the present invention has the function of hypoglycemic, with respect to single aloe vera powder, probiotic or its combination, the effect of composition of the present invention is better in reducing the blood sugar of experimental mice, It shows that the aloe, probiotics and prebiotics in the composition of the present invention have a synergistic effect, and the present invention has obvious technical advantages and significant adjuvant therapeutic effect. the
实施例5:降血糖人体试食实验 Example 5: Hypoglycemic Human Food Trial Experiment
依据卫生部《保健食品检验与评价技术规范(2003年)》,进行降血糖人体试食实验,具体操作如下: According to the "Technical Specifications for Inspection and Evaluation of Health Food (2003)" issued by the Ministry of Health, the human body test food experiment for lowering blood sugar was carried out. The specific operations are as follows:
1、样品: 1. Sample:
本试验的样品由深圳华大基因科技有限公司提供,按本发明的实施例1制备得到软胶囊。 The samples of this test are provided by Shenzhen Huada Gene Technology Co., Ltd., and soft capsules are prepared according to Example 1 of the present invention. the
2、人体试食及试验方法: 2. Human body test food and test method:
按自愿原则选择120例Ⅱ型糖尿病人,其中男性80人,女性40人,年龄范围43-75岁,无严重心肝肾等并发症,采取试食前中后对比设计。受试者原用治疗药物种类、饮食控制及活动不变,按表2的分组情况,每组10人,组1服用对照组、组2服用组合1,组3服用组合2,组4服用组合3,组5服用组合4,组6服用组合5,组7服用组合6,组8服用组合7,组9服用组合8,组10服用组合9,组11服用组合10,组12服用组合11,每日2次,每次3粒,于早、晚饭前服用,连续服用30天。监测病人血压、大小便、体重的变化,并测定空腹和餐后2小时的血糖(用葡萄糖氧化酶法)。 A total of 120 patients with type Ⅱ diabetes mellitus were selected on a voluntary basis, including 80 males and 40 females, aged 43-75 years, with no serious heart, liver and kidney complications. The types of therapeutic drugs, diet control and activities used by the subjects remained unchanged. According to the grouping situation in Table 2, there were 10 people in each group. Group 1 took the control group, group 2 took the combination 1, group 3 took the combination 2, and group 4 took the combination 3. Group 5 took combination 4, group 6 took combination 5, group 7 took combination 6, group 8 took combination 7, group 9 took combination 8, group 10 took combination 9, group 11 took combination 10, group 12 took combination 11, 2 times a day, 3 capsules each time, before breakfast and dinner, for 30 consecutive days. Monitor changes in the patient's blood pressure, urine, and weight, and measure fasting and 2-hour postprandial blood glucose (using the glucose oxidase method). the
3、评判标准: 3. Judging criteria:
显效:基本症状消失,空腹或餐后2小时的血糖较治疗前下降不超过30.0%。 Significant effect: the basic symptoms disappear, and the blood sugar on an empty stomach or 2 hours after a meal drops by no more than 30.0% compared with that before treatment. the
有效:基本症状明显改善,空腹和餐后2小时的血糖较治疗前下降不超过10.0%。 Effective: The basic symptoms are significantly improved, and the blood sugar on an empty stomach and 2 hours after a meal is less than 10.0% lower than that before treatment. the
无效:基本症状无明显改善,空腹和餐后2小时的血糖较治疗前下降小于10.0%。 Ineffective: The basic symptoms did not improve significantly, and the blood sugar on an empty stomach and 2 hours after meals decreased by less than 10.0% compared with before treatment. the
4、人体试食结果 4. Results of human food trials
实验结果如表5所示: The experimental results are shown in Table 5:
表5试吃人群血糖检测结果 Table 5 Blood glucose test results of the trial population
由表5的结果可知,与试食前相比,试食30天本发明的组合物后,病人空腹血糖和餐后2h血糖有明显的降低,较试食前有极显著性差异(P<0.01)。由此表明,本发明的组合物能够通过改善肠道菌群结构从而有效降低血糖,具有明显的降血糖保健功能,并对受试人群健康无损害作用。 From the results in Table 5, it can be known that, compared with before the trial, after 30 days of trial eating the composition of the present invention, the patient's fasting blood sugar and postprandial 2h blood sugar were significantly lowered, which was significantly different than before the trial (P<0.01) . This shows that the composition of the present invention can effectively lower blood sugar by improving the intestinal flora structure, has obvious health care function of lowering blood sugar, and has no harmful effect on the health of the test population. the
在本说明书的描述中,参考术语“一个实施例”、“一些实施例”、“示例”、“具体示例”、或“一些示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本发明的至少一个实施例或示例中。在本说明书中,对上述术语的示意性表述不一定指的是相同的实施例或示例。而且,描述的具体特征、结构、材料或者特点可以在任何的一个或多个实施例或示例中以合适的方式结合。 In the description of this specification, descriptions referring to the terms "one embodiment", "some embodiments", "example", "specific examples", or "some examples" mean that specific features described in connection with the embodiment or example , structure, material or characteristic is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. the
尽管已经示出和描述了本发明的实施例,本领域的普通技术人员可以理解:在不脱离本发明的原理和宗旨的情况下可以对这些实施例进行多种变化、修改、替换和变型,本发明的范围由权利要求及其等同物限定。 Although the embodiments of the present invention have been shown and described, those skilled in the art can understand that various changes, modifications, substitutions and modifications can be made to these embodiments without departing from the principle and spirit of the present invention. The scope of the invention is defined by the claims and their equivalents. the
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