阅读说明：本技术 枳实总酚提取物在肠道保护药物制备上的应用 (Application of total phenols extract of immature bitter orange in preparation of intestinal tract protection medicine ) 是由 刘元艳 刘林林 陈友文 李晨曦 刘蕊 宋钰蓉 刘广知 李文 曹志文 于柳春阳 于 2020-01-07 设计创作，主要内容包括：本发明属于药物新用途技术领域,具体涉及到枳实总酚提取物在肠道保护药物制备上的应用,所述枳实总酚提取物的制备方法为：取枳实粉碎后用,10倍量50％乙醇浸泡30分钟,然后将混合物回流提取1.5小时,重复三次,过80目筛后合并三次提取液,在真空旋转蒸发器中回收乙醇,水提物在真空旋转蒸发器中混合浓缩,在真空烘箱中干燥,得到枳实总酚提取物；所述肠道保护具体为：上调疣微菌科、乳酸菌科、普雷沃氏菌科的生长,抑制毛螺菌科、拟杆菌科、紫单胞菌科和肠杆菌科的生长,保护肠道屏障完整性。与现有技术相比,本发明更精准地针对了具体疾病,使患者在检查出所属病因后,能更明确、快捷选择枳实总酚提取物制剂进行治疗。(The invention belongs to the technical field of new application of medicines, and particularly relates to application of a total phenol extract of immature bitter oranges in preparation of an intestinal tract protection medicine, wherein the preparation method of the total phenol extract of immature bitter oranges comprises the following steps: crushing immature bitter oranges, soaking the crushed immature bitter oranges in 10 times of 50% ethanol for 30 minutes, then carrying out reflux extraction on the mixture for 1.5 hours, repeating the extraction for three times, sieving the mixture for 80 meshes, combining extracting solutions obtained in the three times, recovering the ethanol in a vacuum rotary evaporator, mixing and concentrating the water extract in the vacuum rotary evaporator, and drying the mixed water extract in a vacuum oven to obtain an immature bitter oranges total phenol extract; the intestinal protection is specifically as follows: up-regulating the growth of wart microbiaceae, lactobacillaceae, Prevoteriaceae, inhibiting the growth of pilospiraceae, Bacteroides, Porphyromonaceae and Enterobacteriaceae, and protecting the integrity of intestinal barrier. Compared with the prior art, the invention aims at specific diseases more accurately, so that patients can more clearly and quickly select the total phenol extract preparation of the immature bitter orange for treatment after the disease causes are detected.)

1. An application of total phenols extract of immature bitter orange in preparation of an intestinal tract protection medicament is characterized in that the preparation method of the total phenols extract of immature bitter orange comprises the following steps: crushing immature bitter oranges, soaking the crushed immature bitter oranges in 10 times of 50% ethanol for 30 minutes, then carrying out reflux extraction on the mixture for 1.5 hours, repeating the extraction for three times, sieving the mixture for 80 meshes, combining extracting solutions obtained in the three times, recovering the ethanol in a vacuum rotary evaporator, mixing and concentrating the water extract in the vacuum rotary evaporator, and drying the mixed water extract in a vacuum oven to obtain an immature bitter oranges total phenol extract; the intestinal protection is specifically as follows: up-regulating the growth of wart microbiaceae, lactobacillaceae, Prevoteriaceae, inhibiting the growth of pilospiraceae, Bacteroides, Porphyromonaceae and Enterobacteriaceae, and protecting the integrity of intestinal barrier.

2. The use of total phenols from citrus aurantium as claimed in claim 1 in the preparation of a medicament for the protection of the intestinal tract, wherein the protection is a correction of the structural changes of the intestinal flora caused by antibiotics.

3. The application of the total phenols extract of immature bitter orange in the preparation of an intestinal tract protection medicament as claimed in claim 1, wherein the total phenols extract of immature bitter orange comprises the following components in a crude drug amount of 1 g/ml: neohesperidin 97244453.52ng/ml, naringin 61045773.9ng/ml, hesperidin 20603969.1ng/ml, narirutin 17752304.46ng/ml, hesperetin 3802648.92ng/ml, rhoifolin 2631472.98ng/ml, luteolin 2591288.1ng/ml, nobiletin 2291214.3ng/ml, eriocitrin 2166024.54ng/ml, rutin 852041.22ng/ml, diosmin 629279.22ng/ml, poncirin 520566.96ng/ml, hesperetin 340966.86ng/ml, naringenin 261388.26ng/ml, sinensetin 256528.62ng/ml, 5-nornobiletin 113856.18ng/ml, limonin 97171.56ng/ml, nomilin 50669.22ng/ml, diosgenin-7-O glucoside 34483.38ng/ml, apigenin 19076.58ng/ml, xanthotoxol 09ng/ml, kaempferitrinin 9062.52ng/ml, diosmin 5558.46ng/ml, diosmin 829 4ng/ml, 4218.9ng/ml eriodictyol, 4124.04ng/ml scoparone and 3898.14ng/ml isoanisic acid.

Technical Field

The invention belongs to the technical field of new application of medicines, and particularly relates to application of a total phenol extract of immature bitter oranges in preparation of an intestinal tract protection medicine.

Background

The intestinal flora is a complex, highly dynamic community of microorganisms. It is considered to be an indispensable "metabolic organ" involved in the nutritional processing and production of essential compounds such as short chain fatty acids and bile acids. In addition, the intestinal flora contributes to the maturation of the gastrointestinal system and the development of the immune system. The composition of the intestinal flora is constantly influenced by factors such as genetics, age, sex, diet, antibiotics, environment, etc. The most important of these is the antibiotic, which is widely used in the treatment and prevention of bacterial infections. However, there is increasing evidence that antibiotics have an adverse effect on the physiological function of the host, leading to a structural change in the intestinal flora, a condition known as "gut flora imbalance".

Broad spectrum antibiotics can affect the overall abundance of gut flora composition, resulting in a rapid decline in diversity, uniformity, and categorical richness. Several studies have shown that the use of broad spectrum antibiotics such as ampicillin, clindamycin and vancomycin can lead to a dysbacteriosis of the intestinal flora. The flora plays an important role in maintaining the integrity of the intestinal barrier, which is crucial for the homeostasis and function of intestinal and systemic diseases. The integrity of the intestinal barrier prevents the transfer of bacterial endotoxin from the intestine to the liver. Tight junctions, such as Zonula occludens 1(ZO-1) and Occludin, tightly join intestinal cells together and control cell permeability. Thus, claudin regulates the integrity of the intestinal barrier. In addition to altering intestinal barrier function, antibiotics also alter the function of the intestinal flora.

Immature bitter orange, it is Rutaceae plant sour orange Citrus aurantium L, and its cultivated variety or sweet orange C.sinsisOsbeck's dry young fruit, its taste is bitter, pungent, sour, nature is slightly cold, it is spleen, stomach channel to collect, have effects of breaking qi and resolving food stagnation, it is mainly used for treating stagnation and internal stagnation, stuffiness and pain, it is heavy after diarrhea, stool obstruction, phlegm stagnation and qi obstruction, chest impediment, chest building, organ droop, etc. immature bitter orange medicinal material resource is abundant, distribute extensively, its producing area mainly has Sichuan, Jiangxi, Hunan, Fujian, etc., produce sour orange in the west as the land medicinal material, immature bitter orange Total phenol extract (Total phenol extracts of Citrus aurantium L, TPE-CA) includes flavan and its glycosides, polymethoxylate flavonoids, coumarins (alcohol) and their glycosides, vitamins, citric acid and other bitter substances, it has the function of regulating the human body's health and strengthening the steady state.

Although immature bitter orange is reported to have the effects of invigorating stomach and promoting digestion, the pharmacological actions related to invigorating stomach and promoting digestion are too extensive. For example, the drugs for treating gastric ulcers and gastric obstructions must not be used interchangeably, and immature bitter orange does not only act on gastric diseases. Therefore, the current research is not deep enough for the drugs requiring precise medical treatment. The stomach invigorating and digestion promoting effects of the total phenols extract of the immature bitter orange are analyzed, more accurate pharmacological effects are found, and the research and development of new drugs are facilitated.

Disclosure of Invention

In order to solve the technical problems, the invention provides application of total phenols extract of immature bitter orange in preparation of an intestinal tract protection medicament.

The application of the total phenols extract of immature bitter orange in the preparation of the intestinal tract protection medicine comprises the following steps: crushing immature bitter oranges, soaking the crushed immature bitter oranges in 10 times of 50% ethanol for 30 minutes, then carrying out reflux extraction on the mixture for 1.5 hours, repeating the extraction for three times, sieving the mixture for 80 meshes, combining extracting solutions obtained in the three times, recovering the ethanol in a vacuum rotary evaporator, mixing and concentrating the water extract in the vacuum rotary evaporator, and drying the mixed water extract in a vacuum oven to obtain an immature bitter oranges total phenol extract; the intestinal protection is specifically as follows: up-regulating the growth of wart microbiaceae, lactobacillaceae, Prevoteriaceae, inhibiting the growth of pilospiraceae, Bacteroides, Porphyromonaceae and Enterobacteriaceae, and protecting the integrity of intestinal barrier.

The application of the total phenols extract of immature bitter orange in the preparation of the intestinal tract protection medicament can correct the structural change of intestinal flora caused by antibiotics.

The application of the total phenols extract of immature bitter orange in the preparation of the intestinal tract protection medicine comprises the following components in a crude drug amount of 1 g/ml: neohesperidin 97244453.52ng/ml, naringin 61045773.9ng/ml, hesperidin 20603969.1ng/ml, narirutin 17752304.46ng/ml, hesperetin 3802648.92ng/ml, rhoifolin 2631472.98ng/ml, luteolin 2591288.1ng/ml, nobiletin 2291214.3ng/ml, eriocitrin 2166024.54ng/ml, rutin 852041.22ng/ml, diosmin 629279.22ng/ml, poncirin 520566.96ng/ml, hesperetin 340966.86ng/ml, naringenin 261388.26ng/ml, sinensetin 256528.62ng/ml, 5-nornobiletin 113856.18ng/ml, limonin 97171.56ng/ml, nomilin 50669.22ng/ml, diosgenin-7-O glucoside 34483.38ng/ml, apigenin 19076.58ng/ml, xanthotoxol 09ng/ml, kaempferitrinin 9062.52ng/ml, diosmin 5558.46ng/ml, diosmin 829 4ng/ml, 4218.9ng/ml eriodictyol, 4124.04ng/ml scoparone and 3898.14ng/ml isoanisic acid.

Compared with the prior art, the application of the total phenol extract of immature bitter orange in the preparation of the intestinal tract protection medicament aims at specific diseases more accurately, so that patients can more clearly and quickly select a total phenol extract preparation of immature bitter orange to treat the diseases after the disease causes of the patients are detected.

Drawings

FIG. 1: effect of TPE-CA on antibiotic-induced intestinal microflora composition. Relative abundance at phylum level of blank, antibiotic, TPE-CA and probiotic groups.

FIG. 2: effect of TPE-CA on antibiotic-induced intestinal microflora composition. Relative abundance at class level of blank, antibiotic, TPE-CA and probiotic groups.

FIG. 3: effect of TPE-CA on intestinal barrier integrity. A, the endotoxin expression levels of blank group, antibiotic group, TPE-CA group and probiotic group. B, expression levels of a blank group, an antibiotic group, a TPE-CA group and a probiotic group ZO-1. C, expression levels of placebo, antibiotics, TPE-CA, probiotic Ocplus. P <0.05, p <0.01, p <0.001, compared to the control group. Data are expressed as mean ± standard deviation, 10 animals per group.

Detailed Description

The following will further illustrate the application of the total phenols extract of citrus aurantium to the preparation of a drug for protecting the intestinal tract, but the scope of the present invention is not limited thereto.