CN115088833A - A functional food for preventing and/or treating intestinal damage in tumor patients - Google Patents
A functional food for preventing and/or treating intestinal damage in tumor patients Download PDFInfo
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- CN115088833A CN115088833A CN202210553684.2A CN202210553684A CN115088833A CN 115088833 A CN115088833 A CN 115088833A CN 202210553684 A CN202210553684 A CN 202210553684A CN 115088833 A CN115088833 A CN 115088833A
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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Abstract
Description
技术领域technical field
本发明属于功能性配方食品技术领域,具体涉及一种用于预防和/或治疗肿瘤患者肠道损伤的功能性食品。The invention belongs to the technical field of functional formula foods, and in particular relates to a functional food for preventing and/or treating intestinal damage in tumor patients.
背景技术Background technique
恶性肿瘤患者营养-代谢失衡常见状态包括,热量摄入严重不足,蛋白质摄入不足而需求大幅增多导致肌肉萎缩,机体组织修复的需求增高,发生以菌群多样性发生显著改变为突出表现的肠道菌群失调,微量营养素缺乏及电解质紊乱,机体处于高血凝状态。肿瘤食品在辅助治疗肿瘤患者肠道菌群失调、营养素缺乏的不良临床表现、癌性恶液质、高血糖、胰岛素抵抗、高血脂等肿瘤代谢综合征、高血凝状态、放射性肠炎,和辅助维护、修复肠功能障碍方面发挥着作用。Common states of nutritional-metabolic imbalance in patients with malignant tumors include severe insufficiency of calorie intake, insufficient protein intake and a substantial increase in demand leading to muscle atrophy, increased demand for tissue repair, and the occurrence of intestinal flora characterized by significant changes in flora diversity. Dysbiosis, micronutrient deficiency and electrolyte imbalance, the body is in a hypercoagulable state. Tumor food is used in adjuvant treatment of tumor patients with intestinal flora imbalance, adverse clinical manifestations of nutrient deficiency, cancer cachexia, hyperglycemia, insulin resistance, hyperlipidemia and other tumor metabolic syndromes, hypercoagulable state, radiation enteritis, and adjuvant therapy. It plays a role in maintaining and repairing intestinal dysfunction.
特别对于慢性病的肿瘤造成营养不良,就是疾病恶化、恢复缓慢、患者痛苦的根源。为满足肿瘤患者进食受限、代谢紊乱、消化吸收障碍对营养素或膳食的特殊需求,配制加工而成的配方食品,可用于纠正癌性营养不良带来的后继不良反应。并且肿瘤的常规化疗药物5-FU在治疗过程中会在细胞内转变为5-氟尿嘧啶脱氧核苷酸(5F-dUMP),而抑制脱氧胸苷酸合成酶,阻止脱氧尿苷酸(dUMP)甲基化转变为脱氧胸苷酸(dTMP),从而影响DNA的合成。并且有文献统计显示,大约有50%-80%的患者在治疗过程中会患上肠道炎症等疾病,且伴有胃肠道反应,其表现为食欲减退、恶心、呕吐、口腔炎、胃炎、腹泻,严重者甚至还会出现血性腹泻。因此需密切关注患者营养状况,按时行营养状况评价与筛查,针对肿瘤患者所处的疾病阶段和肿瘤的不同位置,选择营养治疗与辅助的施用程度。营养治疗的地位等同于手术、放疗、药物治疗等抗肿瘤治疗,注重营养代谢治疗,就是减轻患者痛苦、节省费用、改善生活质量。目前市面上针对肿瘤患者的肠道炎症等胃肠道疾病的营养制剂营养成分含量仍较为单一且种类较为稀少。Malnutrition, especially for chronically ill tumors, is the source of disease progression, slow recovery, and patient suffering. In order to meet the special needs of cancer patients for nutrients or diets with restricted eating, metabolic disorders, and digestive and absorption disorders, formula foods prepared and processed can be used to correct subsequent adverse reactions caused by cancerous malnutrition. In addition, the conventional chemotherapy drug 5-FU of tumors will be converted into 5-fluorouracil deoxynucleotide (5F-dUMP) in the cell during the treatment process, which inhibits deoxythymidylate synthase and prevents deoxyuridylic acid (dUMP) methylation. The methylation is converted to deoxythymidylate (dTMP), which affects DNA synthesis. And literature statistics show that about 50%-80% of patients will suffer from intestinal inflammation and other diseases during treatment, accompanied by gastrointestinal reactions, which are manifested as loss of appetite, nausea, vomiting, stomatitis, gastritis. , diarrhea, and even bloody diarrhea in severe cases. Therefore, it is necessary to pay close attention to the nutritional status of patients, conduct nutritional status evaluation and screening on time, and select the degree of nutritional therapy and adjuvant administration according to the disease stage of tumor patients and the different locations of the tumor. The status of nutritional therapy is equivalent to anti-tumor therapy such as surgery, radiotherapy, and drug therapy. Focusing on nutritional metabolism therapy is to relieve patients' pain, save costs, and improve the quality of life. At present, the nutritional content of nutritional preparations for gastrointestinal diseases such as intestinal inflammation in tumor patients is still relatively single and the types are relatively rare.
发明内容SUMMARY OF THE INVENTION
本发明的目的是提供一种用于预防和/或治疗肿瘤患者肠道损伤的功能性食品。The purpose of the present invention is to provide a functional food for preventing and/or treating intestinal damage in tumor patients.
为了实现上述目的,本发明采用以下技术方案:In order to achieve the above object, the present invention adopts the following technical solutions:
一种功能性食品,每100g中含:乳清蛋白粉8-9g、大豆分离蛋白5-7g、菜籽油粉6-8g、椰子油粉4-7g、低聚果糖20-25g、麦芽糊精25-30g、抗性糊精25-28g、菊粉0.15g-0.4g、葡萄糖酸钾0.1-0.3g、维生素B6 0.004-0.006g、维生素D3 100-115IU、维生素B1 0.0025-0.004g、柠檬酸锌0.002-0.0035g、柠檬酸锰0.0028-0.004g、氯化钠0.002-0.005g、玉米粉0.3-0.5g、人参皂苷5-8g。A functional food, each 100g contains: whey protein powder 8-9g, soybean protein isolate 5-7g, rapeseed oil powder 6-8g, coconut oil powder 4-7g, fructooligosaccharide 20-25g, malt paste Essence 25-30g, Resistant Dextrin 25-28g, Inulin 0.15g-0.4g, Potassium Gluconate 0.1-0.3g, Vitamin B6 0.004-0.006g, Vitamin D3 100-115IU, Vitamin B1 0.0025-0.004g, Lemon Zinc acid 0.002-0.0035g, manganese citrate 0.0028-0.004g, sodium chloride 0.002-0.005g, corn flour 0.3-0.5g, ginsenoside 5-8g.
上述功能性食品在制备预防和/或治疗肿瘤患者肠道损伤的产品中的应用。The application of the above functional food in the preparation of a product for preventing and/or treating intestinal damage in tumor patients.
本发明将功能性配方食品应用于制备预防和/或治疗肿瘤患者肠道损伤的食品制剂方面,所述的功能性配方食品用于改善病人肠道损伤,改善病人食欲及营养吸收,从而增进后续肿瘤治疗效果,从而为制备预防和/或治疗肿瘤患者肠道损伤的食品制剂方面提供了一种新来源,同时也发掘出了这种功能性配方食品的新的药用价值。In the present invention, functional formula food is applied to the preparation of food preparations for preventing and/or treating intestinal damage of tumor patients. Therefore, it provides a new source for the preparation of food preparations for preventing and/or treating intestinal damage in tumor patients, and also discovers the new medicinal value of this functional formula food.
附图说明Description of drawings
图1为给药15天后各组小鼠肿瘤体积的统计结果。Figure 1 shows the statistical results of tumor volume of mice in each group 15 days after administration.
图2为给药15天后各组小鼠肿瘤体积的照片。Figure 2 is a photograph of the tumor volume of mice in each group 15 days after administration.
具体实施方式Detailed ways
下面结合附图和具体实施例对本发明作进一步详细说明,但不应理解为对本发明的限制。在不背离本发明精神和实质的情况下,对本发明方法、步骤或条件所作的修改或替换,均属于本发明的范围。实施例中未注明具体条件的实验方法及未说明配方的试剂均为按照本领域常规条件。The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments, but should not be construed as a limitation of the present invention. Modifications or substitutions made to the methods, steps or conditions of the present invention without departing from the spirit and essence of the present invention all belong to the scope of the present invention. In the examples, the experimental methods without specifying the specific conditions and the reagents without specifying the formula are all in accordance with the conventional conditions in the art.
实施例1Example 1
1.试剂及动物:1. Reagents and animals:
功能性配方食品:每100g配方食品中(氨基酸型、短肽型蛋白质,占比10-15%;长链甘油三酯LCT、中链甘油三酯MCT所组成的脂肪部分占比10-16%;碳水化合物主要包含糊精及一定成分的食物淀粉,占比为70-73%,同时添加了人体必需的多种维生素、矿物质和微量元素;人参皂苷由人参属药物内提取,占比5-8%):乳清蛋白粉8.5g、大豆分离蛋白6g、菜籽油粉7g、椰子油粉6g、低聚果精22g、麦芽糊精25g、抗性糊精25g、菊粉0.3g、葡萄糖酸钾0.2g、维生素B6 0.005g、维生素D3 110IU、维生素B1 0.003g、柠檬酸锌0.003g、柠檬酸锰0.003g、氯化钠0.004g、玉米粉0.4g、人参皂苷6g。Functional formula food: per 100g formula food (amino acid type, short peptide type protein, accounting for 10-15%; long-chain triglyceride LCT, medium-chain triglyceride MCT The fat part constitutes 10-16% ;Carbohydrates mainly include dextrin and certain ingredients of food starch, accounting for 70-73%, at the same time adding a variety of vitamins, minerals and trace elements necessary for the human body; Ginsenosides are extracted from ginseng drugs, accounting for 5 -8%): Whey Protein Powder 8.5g, Soy Protein Isolate 6g, Rapeseed Oil Powder 7g, Coconut Oil Powder 6g, Oligofructose 22g, Maltodextrin 25g, Resistant Dextrin 25g, Inulin 0.3g, Potassium gluconate 0.2g, vitamin B6 0.005g, vitamin D3 110IU, vitamin B1 0.003g, zinc citrate 0.003g, manganese citrate 0.003g, sodium chloride 0.004g, corn flour 0.4g, ginsenoside 6g.
实验动物:实验用成年雄性C57BL/6小鼠,8-10周龄,体重25-30g,购置于上海实验动物中心,SPF级别动物饲养于南通大学实验动物中心,实验动物室温度20~26℃(日温差≤4℃),湿度40%~70%,照明12h:12h明暗交替。Experimental animals: Adult male C57BL/6 mice, 8-10 weeks old, weighing 25-30 g, were purchased in Shanghai Experimental Animal Center, SPF animals were raised in Nantong University Experimental Animal Center, and the temperature in the laboratory animal room was 20-26 °C (Daily temperature difference≤4℃), humidity 40%~70%, lighting 12h: 12h alternating light and dark.
2.实验内容:2. Experiment content:
动物分组:肿瘤模型组(A),肿瘤模型+5-FU组(B),肿瘤模型+5-FU+功能配方组(C),肿瘤模型+5-FU+怡补康阳性对照组(D)。小鼠肿瘤干预后,将其分为4组,每组6只,根据组别随机分配。Animal groups: tumor model group (A), tumor model + 5-FU group (B), tumor model + 5-FU + functional formula group (C), tumor model + 5-FU + Yibukang positive control group (D). After tumor intervention, the mice were divided into 4 groups with 6 mice in each group, and were randomly assigned according to the group.
分组设计如表1所示。The grouping design is shown in Table 1.
表1Table 1
3.试验方法:3. Test method:
手术操作如下:The operation is as follows:
(1)建立小鼠肿瘤模型方法如下:取对数生长期的CT26.WT细胞制备成单细胞悬液,细胞密度为1×1010个/L,抽取0.1mL,即接种细胞数为1×106个,接种于近交系BALB/c小鼠右腋下。10d后长出直径约1cm的实体瘤。建立小鼠CT26.WT结肠癌原位移植瘤模型:首先处死皮下荷瘤小鼠,皮肤消毒,剥离皮下肿瘤,立即浸入含青霉素、链霉素各100U/mL的生理盐水中,剔除周围结缔组织,取肿瘤生长旺盛的鱼肉状组织,剪碎成1mm3大小的瘤块备用。将C57BL/6小鼠分别称重,2%戊巴比妥钠100mg/kg右侧腹腔内注射麻醉后取仰卧位,固定四肢,乙醇消毒腹部术野。左下腹部切口约1cm,将切口右侧皮肤及皮下层稍作游离,显露盲结肠,拖出至皮下,关闭其上下缘的腹腔。用4号针头轻轻刮去盲结肠交界处少许浆膜,有血液渗出,选取1粒已制备好的瘤块贴于划破处,用Histoacryl医用组织胶水黏合,将外置肠段回纳入腹,缝合腹壁。整个过程遵循无菌操作原则。小鼠清醒后置于SPF级动物房中常规饲养。(1) The method for establishing a mouse tumor model is as follows: take CT26.WT cells in logarithmic growth phase to prepare a single cell suspension, the cell density is 1×10 10 cells/L, and extract 0.1 mL, that is, the number of inoculated cells is 1× 10 6 were inoculated into the right armpit of inbred BALB/c mice. After 10 days, a solid tumor with a diameter of about 1 cm grew. To establish the mouse CT26.WT colon cancer orthotopic transplantation tumor model: firstly, the subcutaneous tumor-bearing mice were sacrificed, the skin was disinfected, the subcutaneous tumor was peeled off, and the subcutaneous tumor was immediately immersed in 100 U/mL normal saline containing penicillin and streptomycin, and the surrounding connective tissue was removed. , Take the fish-like tissue with vigorous tumor growth and cut it into pieces of 1mm 3 size for use. The C57BL/6 mice were weighed and anaesthetized by intraperitoneal injection of 2% sodium pentobarbital 100 mg/kg on the right side. The left lower abdominal incision was made about 1 cm, and the skin and subcutaneous layer on the right side of the incision were slightly dissociated to expose the cecum, drag it out to the subcutaneous, and close the abdominal cavity at the upper and lower edges of the incision. Use a 4-gauge needle to gently scrape off a little serosa at the junction of the cecum and colon, if there is blood exudation, select 1 prepared tumor mass and stick it to the incision, glue it with Histoacryl medical tissue glue, and put the external intestinal segment back in. Abdominal, suture the abdominal wall. The whole process follows the principle of aseptic operation. After awake, the mice were placed in a SPF animal room and reared routinely.
(2)选取造模成功的小鼠随机分组,随机分为四组,每组6只,分为肿瘤模型组,肿瘤模型+5-FU组,肿瘤模型+5-FU+功能配方组,肿瘤模型+5-FU+怡补康阳性对照组。这三组隔两天腹腔注射一次氟尿嘧啶溶液(30mg·kg-1),肿瘤模型组在试验期间每天灌胃给予等体积生理盐水,此操作连续进行15天。(2) Select the mice with successful modeling and randomly divide them into four groups, with 6 mice in each group, divided into tumor model group, tumor model + 5-FU group, tumor model + 5-FU + functional formula group, tumor model +5-FU + Yibukang positive control group. The three groups were intraperitoneally injected with fluorouracil solution (30 mg·kg -1 ) every two days, and the tumor model group was given an equal volume of normal saline by gavage every day during the experiment, and this operation was continued for 15 days.
(3)造模成功后第二天给药,肿瘤模型+5-FU+功能配方组,肿瘤模型+5-FU+怡补康阳性对照组按同等热量给予同等剂量的功能性配方食品、怡补康营养制剂,其余两组给予相同热量的饲料。(3) The drug was administered on the second day after the successful modeling. The tumor model + 5-FU + functional formula group and the tumor model + 5-FU + Yibukang positive control group were given the same dose of functional formula food and Yibukang according to the same calories. Nutritional preparations, the other two groups were given the same calorie feed.
4.观察指标4. Observation Metrics
一般状态观察:观察时间和频率:给药前后每天固定时间观察1次;观察结果:给药期受试动物整体状态。General state observation: observation time and frequency: observed once a day at a fixed time before and after administration; observation results: the overall state of the test animals during the administration period.
处理4周,观察小鼠形态及肿瘤体积变化、检测血浆营养指标、炎症指标、免疫指标、氮平衡、血细胞计数、血浆蛋白的变化。After 4 weeks of treatment, the changes in the morphology and tumor volume of the mice were observed, and the changes in plasma nutritional indexes, inflammatory indexes, immune indexes, nitrogen balance, blood cell counts, and plasma proteins were detected.
(1)小鼠形态及肿瘤体积变化(1) Changes of mouse morphology and tumor volume
每天观察小鼠外观,包括毛色,摄食饮水,精神状态以及活动情况。同时,每7天记录一次小鼠体重;每3天测量一次肿瘤的大小,计算其肿瘤The appearance of the mice, including coat color, food and water intake, mental state and activity, were observed every day. At the same time, the body weight of the mice was recorded every 7 days; the size of the tumor was measured every 3 days, and the tumor was calculated.
体积。volume.
肿瘤体积(mm)=长(mm)×宽(mm)×高(mm)/2。Tumor volume (mm)=length (mm)×width (mm)×height (mm)/2.
给药结束后次日,将小鼠颈椎脱臼处死,剥离出肿瘤块称重记录。The next day after the administration, the mice were sacrificed by cervical dislocation, and the tumor mass was removed and weighed for recording.
(2)营养指标(2) Nutritional indicators
分别在造模成功后第1、2、3、4w禁食12h后,心脏取血,加入1%EDTA二钠溶液抗凝,3000r/min离心5min,取上清液,用全自动生化分析仪测定血浆总蛋白(Total Protein,TP)和白蛋白(Albumin,Alb)浓度。After 1, 2, 3, and 4 weeks of fasting for 12 hours after successful modeling, blood was collected from the heart, anticoagulated by adding 1% disodium EDTA solution, centrifuged at 3000 r/min for 5 min, and the supernatant was taken with an automatic biochemical analyzer. Plasma total protein (Total Protein, TP) and albumin (Albumin, Alb) concentrations were determined.
(3)炎症指标(3) Inflammatory indicators
分别在造模成功后第1、2、3、4w禁食12h后,心脏取血,加入1%EDTA二钠溶液抗凝,3000r/min离心5min,取上清液,用ELISAAfter 1, 2, 3, and 4 weeks of fasting for 12 hours after successful modeling, blood was collected from the heart, anticoagulated by adding 1% disodium EDTA solution, centrifuged at 3000 r/min for 5 min, and the supernatant was taken for ELISA.
试剂盒测定小鼠肿瘤坏死因子(Tumor Necrosis Factor,TNF-α)和白细胞介素-2(Interleukin-2,IL-2)水平。The kits were used to measure the levels of tumor necrosis factor (Tumor Necrosis Factor, TNF-α) and interleukin-2 (Interleukin-2, IL-2) in mice.
(4)免疫指标(4) Immune indicators
分别在造模成功后第1、2、3、4w禁食12h后,心脏取血,加入1%EDTA二钠溶液抗凝,3000r/min离心5min,取上清液,用ELISAAfter 1, 2, 3, and 4 weeks of fasting for 12 hours after successful modeling, blood was collected from the heart, anticoagulated by adding 1% disodium EDTA solution, centrifuged at 3000 r/min for 5 min, and the supernatant was taken for ELISA.
试剂盒测定小鼠Ig G、Ig A和Ig M的水平。The kit measures the levels of IgG, IgA and IgM in mice.
5.统计分析5. Statistical analysis
试验数据以Mean±SD表示,多组之间采用one-way ANOVA检验(M-W法)对组间差异进行比较。统计学分析结果*P<0.05认为有显著性差异,**P<0.01以及***P<0.001认为有极显著性差异。The test data were expressed as Mean±SD, and the differences between groups were compared by one-way ANOVA test (M-W method). Statistical analysis results *P<0.05 considered significant difference, **P<0.01 and ***P<0.001 considered extremely significant difference.
6.实验结果:6. Experimental results:
由图1、2显示,在给药十五天以后,与肿瘤模型组相比,肿瘤模型+5-FU组(###P<0.001),肿瘤模型+5-FU+功能配方组(####P<0.0001),肿瘤模型+5-FU+怡补康阳性对照组(###P<0.001),以上数据说明,接受用药治疗的组别肿瘤体积均明显减小。同时将肿瘤模型+5-FU+功能配方组与肿瘤模型+5-FU组(**P<0.01)、肿瘤模型+5-FU+怡补康阳性对照组(*P<0.05)作比较,以上说明,本发明功能性配方可有效减小肿瘤体积,且其效果显著优于怡补康营养制剂。As shown in Figures 1 and 2, after 15 days of administration, compared with the tumor model group, the tumor model+5-FU group (###P<0.001), the tumor model+5-FU+functional formula group (###P<0.001). ##P<0.0001), tumor model + 5-FU + Yibukang positive control group (###P<0.001), the above data shows that the tumor volume of the groups receiving drug treatment was significantly reduced. At the same time, the tumor model + 5-FU + functional formula group was compared with the tumor model + 5-FU group (**P<0.01) and the tumor model + 5-FU + Yibukang positive control group (*P<0.05). , the functional formula of the present invention can effectively reduce the tumor volume, and its effect is significantly better than that of the Yibukang nutritional preparation.
本发明通过制备功能性配方食品用于预防和/或肿瘤患者肠道损伤的系列实验研究,结果表明功能性配方食品功能性配方食品显著提高了患者食欲促进了患者营养成分的摄入并且对肠道功能有明显的保护作用,为肿瘤患者的药物研究提供了新的思路。The present invention prepares functional formula food for preventing and/or a series of experimental studies on the intestinal injury of tumor patients, the results show that functional formula food functional formula food significantly improves the patient's appetite, promotes the intake of nutrients in the patient, and has a good effect on the intestinal tract. The tract function has obvious protective effect, which provides a new idea for the drug research of tumor patients.
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