CN113519850A

CN113519850A - Tumor total nutrient emulsion, preparation method and application thereof

Info

Publication number: CN113519850A
Application number: CN202110375894.2A
Authority: CN
Inventors: 覃倩倩; 李佳南; 赖必辉; 陈云; 俞伟祖
Original assignee: Inner Mongolia Mengniu Dairy Group Co Ltd
Current assignee: Inner Mongolia Mengniu Dairy Group Co Ltd
Priority date: 2020-04-13
Filing date: 2021-04-08
Publication date: 2021-10-22

Abstract

The invention relates to a tumor total nutrient emulsion, a preparation method and application thereof. The tumor total nutrient emulsion comprises 10.0-18.0 g/100mL of carbohydrate, 4-17 g/100mL of fat, 7-13 g/100mL of protein and 1.0-2.5 g/100mL of dietary fiber. The invention combines the conditions of abnormal energy consumption, abnormal carbohydrate metabolism, abnormal fat metabolism and abnormal protein and amino acid metabolism of a tumor patient in a specific disease state, has reasonable proportion range of energy density to the product and energy supply ratio to the protein, the fat and the carbohydrate, reduces gluconeogenesis, increases insulin sensitivity, reduces insulin resistance and inflammatory response, and is more suitable for the tumor patient with insulin resistance.

Description

Tumor total nutrient emulsion, preparation method and application thereof

Technical Field

The invention belongs to the field of formula foods with special medical application, and particularly relates to a tumor total nutrient emulsion.

Background

Tumor is a new organism formed by abnormal proliferation and differentiation caused by that cells of local tissues lose normal regulation and control on the growth of the cells at the gene level under the action of various tumorigenic factors of an organism. According to the latest data of 'annual report of Chinese tumor registration in 2013', the number of new cancer cases is about 312 thousands every year in China, and 6 people are diagnosed as malignant tumors every minute. Each year, about 270 million cases of cancer deaths occur nationwide, with 5 people dying from cancer per minute. 20% of new cancer patients worldwide are in China, and 24% of cancer-dead patients are in China. Tumors have become a common disease. The insulin resistance problem is mostly existed in the tumor, especially in the patients with digestive tract cancer, colon cancer, gastric cancer, liver cancer and lung cancer. The disturbance of carbohydrate metabolism in the body causes the enhancement of protein decomposition and the acceleration of fat mobilization, and is also an important reason for the cachexia of patients with advanced malignant tumors. Research shows that although fasting blood sugar of patients with advanced malignant digestive system tumor is not obviously increased, blood sugar of the patients with advanced malignant digestive system tumor is obviously higher than that of a normal control group after taking sugar for 2 hours, which indicates that the malignant tumor patients have a barrier to effective utilization of external glucose. The fasting blood sugar of the patient with the advanced malignant digestive system tumor is not increased, and may be related to the absolute deficiency of the sugar nutrition taken by the patient from food. In addition, the fasting lactic acid of the patient with advanced malignant digestive system tumor is obviously higher than that of the normal control group, which indicates that the glycometabolism of the patient with advanced malignant digestive system tumor is mainly carried out in a glycolysis mode. Lactic acid is a major product of glycolysis, is a major cause of metabolic acidosis, and is an important manifestation of impaired efficient glucose utilization. The steady-state insulin resistance index of the malignant tumor patient is obviously higher than that of the normal control group, but the insulin secretion index is obviously lower than that of the normal control group, which indicates that the glucose metabolism disorder of the malignant digestive system tumor patient in the late stage is related to insulin resistance and insulin secretion function. Insulin resistance in patients with malignant tumors may be associated with the increase of various cytokines, insulin receptor signaling disorders, inflammatory mediators, and islet beta cell apoptosis in the body of the patients.

The clinical nutritional support for tumor patients mainly comprises enteral nutrition and parenteral nutrition. Parenteral nutrition is generally an intravenous drip parenteral nutrition preparation, and such products are inconvenient to operate by intravenous injection compared with enteral nutrition; secondly, the proportion is calculated according to the illness state of the patient, so that the labor cost and the time cost are high; in the practical application process, the effective utilization of glucose by patients is hindered, so that the blood sugar condition and the insulin level of the patients are inevitably monitored in real time, and the medicines, electrolytes, glucose and the like are used for real-time adjustment, thereby increasing the medicine burden and the water intake burden of the patients. Enteral nutrition is generally an oral total nutrient supplement, such as a total nutrient or tumor total nutrient product. The existing total nutrient products on the market are designed according to the conventional requirements of GB29922 special medical application formula food general rule, but not aiming at specific diseases, so that the nutrition of tumor patients cannot be supplemented in a targeted and accurate manner, and the effect is general. The tumor total nutrient formula food on the market is a product (generally powder) designed aiming at the nitrogen balance and the immune condition of a tumor patient on the basis of a total nutrient formula of GB29922 special medical application formula food general rule. However, the products do not carry out design analysis on insulin resistance of patients, and most of tumor patients have the problem of insulin resistance in clinic. If the product is directly taken, the acid-base balance disorder, the large blood sugar fluctuation or the blood sugar disorder of a patient can be caused, and the life of the patient is threatened, so that the application of the product to the insulin resistant malignant tumor patient in clinic is unknown, and the safety and the risk are unknown, thereby greatly limiting the use of the product.

There is a need in the art for a tumor-nutritionally complete emulsion for insulin-resistant malignancies.

Disclosure of Invention

On the basis of the law, guideline and expert consensus, the invention carries out deep research on the hospitalized malignant tumor patients, combines the tumor treatment, the organism metabolic condition and the basic disease condition, analyzes and collates the insulin resistance and the blood sugar condition of the patients in the treatment methods of operation, radiotherapy, chemotherapy, biological target treatment and the like, designs a tumor total nutrient emulsion suitable for the insulin resistance type malignant tumor patients, and is particularly suitable for daily total nutrient supplement of the insulin resistance type malignant tumor patients with digestive tract cancer, colon cancer, gastric cancer, liver cancer and lung cancer.

In one aspect, the invention provides a tumor total nutrient emulsion, which comprises 10.0-18.0 g/100mL carbohydrate, 4-17 g/100mL fat, 7-13 g/100mL protein and 1.0-2.5 g/100mL dietary fiber.

In one embodiment, the tumor total nutrient emulsion comprises 10.0-18.0 g/100mL carbohydrate, 4-17 g/100mL fat, 8-13 g/100mL protein, and 1.0-2.5 g/100mL dietary fiber.

In one embodiment, the ratio of carbohydrate to dietary fiber ranges from 6:1 to 12: 1.

In one embodiment, the protein energy supply ratio is 15% to 35%, the fat energy supply ratio is 20% to 50%, the carbohydrate energy supply ratio is 30% to 50%, and the energy density is 1.2 to 2.5 kcal/mL.

In one embodiment, the osmotic pressure of the tumor total nutrient emulsion is 300-.

In one embodiment, the carbohydrate is selected from the group consisting of maltodextrin, sucrose and isomalto-oligosaccharide.

In one embodiment, the dietary fiber is a resistant dextrin.

In one embodiment, the protein is selected from the group consisting of hydrolyzed soy protein, soy protein isolate, hydrolyzed whey protein, concentrated whey protein, sodium caseinate, and calcium caseinate.

In one embodiment, the content of arginine in the protein is 580-1040 mg, the content of leucine in the protein is 600-1060 mg, the content of glutamic acid in the protein is 1600-2600 mg, and the content of essential amino acid in the protein is 3900-6370 mg per 100mL of the tumor total nutrient emulsion.

In one embodiment, the protein is a 1:5 to 18:1 combination of soy protein isolate and concentrated whey protein. For example, the ratio of soy protein isolate to concentrated whey protein may be 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10: 1.

In one embodiment, the fat is selected from the group consisting of corn oil, sunflower oil, canola oil, medium chain triglycerides, and fish oil.

In one embodiment, the tumor total nutrient emulsion has an osmotic pressure of 300-. In one embodiment, the tumor total nutrient emulsion has a protein energy supply ratio of 15-35%, a fat energy supply ratio of 20-50%, a carbohydrate energy supply ratio of 30-50%, an energy density of 1.2-2.5 kcal/mL, an osmotic pressure of 300-500msom/L, and a pH of 7.0-7.7.

In one embodiment, the tumor total nutrient emulsion comprises 0.1-0.4g/100mL vitamins, 0.9-3.6g/100mL minerals, 0.07-0.27g/100mL choline, and food additives.

In one embodiment, the vitamin is selected from the group consisting of vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, vitamin B₁Vitamin B₂Vitamin B₆Vitamin B₁₂Nicotinic acid species, folic acid, pantothenic acid, biotin, and taurine.

In one embodiment, vitamin a is selected from retinyl acetate, retinyl palmitate, beta-carotene, and all-trans retinol.

In one embodiment, the vitamin C is selected from the group consisting of L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, potassium L-ascorbate, and ascorbyl-6-palmitate.

In one embodiment, the vitamin D is selected from ergocalciferol and cholecalciferol.

In one embodiment, the vitamin E is selected from the group consisting of d-alpha-tocopherol, dl-alpha-tocopherol, d-alpha-tocopherol acetate, dl-alpha-tocopherol acetate, mixed tocopherol concentrates, d-alpha-tocopherol succinate, and dl-alpha-tocopherol succinate.

In one embodiment, vitamin K₁The content of (b) is 0.01-0.05mg/100 mL. In one embodiment, vitamin K₁Is plant menadione.

In one embodiment, vitamin B₁Selected from thiamine hydrochloride and thiamine nitrate.

In one embodiment, vitamin B₂Selected from riboflavin and riboflavin-5' -sodium phosphate.

In one embodiment, vitamin B₆Selected from pyridoxine hydrochloride and pyridoxal 5' -phosphate.

In one embodiment, vitamin B₁₂Selected from cyanocobalamin, cyanocobalamin hydrochloride and hydroxocobalamin.

In one embodiment, the niacin-type substance is selected from niacin and niacinamide.

In one embodiment, the choline is selected from choline chloride and choline bitartrate.

In one embodiment, vitamin A is present in an amount of 0.08 to 2.9mg/100 mL.

In one embodiment, the vitamin C is present in an amount of 40-300mg/100 mL.

In one embodiment, vitamin D is present in an amount of 0.002 to 2.7mg/100 mL.

In one embodiment, the vitamin E is present in an amount of 5.5 to 42mg/100 mL.

In one embodiment, vitamin B₁The content of (b) is 0.2-0.9mg/100 mL.

In one embodiment, vitamin B₂The content of (b) is 0.25-0.9mg/100 mL.

In one embodiment, vitamin B₆The content of (b) is 0.3-1.3mg/100 mL.

In one embodiment, vitamin B₁₂The content of (B) is 0.001-0.006mg/100 mL.

In one embodiment, the niacin species is present in an amount of 2-7.2mg/100 mL.

In one embodiment, folic acid is present in an amount of 0.03 to 0.13mg/100 mL.

In one embodiment, the pantothenate is present in an amount from 0.97 to 3.88mg/100 mL.

In one embodiment, biotin is present in an amount of 0.01 to 0.03mg/100 mL.

In one embodiment, taurine is present in an amount of 10-37mg/100 mL.

In one embodiment, the mineral is selected from the group consisting of sodium, potassium, copper, magnesium, iron, zinc, manganese, calcium, phosphorus, iodine, and selenium.

In one embodiment, the sodium is selected from the group consisting of sodium bicarbonate, sodium dihydrogen phosphate, sodium citrate, sodium chloride, and disodium hydrogen phosphate.

In one embodiment, the potassium is selected from the group consisting of potassium gluconate, potassium citrate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate and potassium chloride.

In one embodiment, the copper is selected from copper sulfate, copper gluconate, copper citrate and copper carbonate.

In one embodiment, the magnesium is selected from the group consisting of magnesium sulfate, magnesium chloride, magnesium oxide, magnesium carbonate, magnesium hydrogen phosphate, and magnesium gluconate.

In one embodiment, the iron is selected from the group consisting of ferrous sulfate, ferrous gluconate, ferric ammonium citrate, ferrous fumarate, ferric citrate, and ferric pyrophosphate.

In one embodiment, the zinc is selected from the group consisting of zinc sulfate, zinc gluconate, zinc oxide, zinc lactate, zinc citrate, zinc chloride, and zinc acetate.

In one embodiment, the manganese is selected from manganese sulfate, manganese chloride, manganese carbonate, manganese citrate, and manganese gluconate.

In one embodiment, the calcium is selected from the group consisting of calcium carbonate, calcium gluconate, calcium citrate, calcium lactate, calcium hydrogen phosphate, calcium chloride, tricalcium phosphate, calcium glycerophosphate, calcium oxide, and calcium sulfate.

In one embodiment, the phosphorus is selected from tricalcium phosphate and calcium hydrogen phosphate.

In one embodiment, the iodine is selected from the group consisting of potassium iodate, potassium iodide, and sodium iodide.

In one embodiment, the selenium is selected from sodium selenate and sodium selenite.

In one embodiment, the tumor total nutrient emulsion comprises 168-673mg/100mL sodium chloride and 114-456mg/100mL sodium citrate; 113-452mg/100mL potassium citrate and 249-998mg/100mL dipotassium hydrogen phosphate; 0.7-2.9mg/100mL copper sulfate; 71-285mg/100mL magnesium carbonate; ferric pyrophosphate of 3.8-15.5mg/100 mL; 1.5-6.4mg/100mL zinc sulfate; 0.7-3mg/100mL manganese sulfate; 120-484mg/100mL calcium carbonate; 56-227mg/100mL calcium hydrogen phosphate; potassium iodide 0.02-0.06mg/100 mL; and/or 0.01-0.06mg/100mL sodium selenite.

In one embodiment, the food additive is selected from sucralose, stabilizers, and flavors.

In one embodiment, the tumor whole nutrient emulsion has a pH of 7.0-7.7, e.g., 7.1, 7.2, 7.3, 7.4, 7.5, or 7.6.

In another aspect, the present invention provides a method for preparing a tumor total nutrient emulsion, comprising:

(1) mixing the protein powder and a portion of the carbohydrate, hydrating and emulsifying;

(2) dissolving the stabilizer with another part of the carbohydrate, adding a fat source to dissolve, and

(3) mineral packs were added followed by vitamin packs.

In still another aspect, the present invention provides the use of the tumor total nutrient emulsion in the preparation of a food composition for treating insulin resistant tumors, tumor associated diabetes, non-diabetic stress hyperglycemia tumors, digestive tract tumors.

In one embodiment, the tumor is esophageal, gastric, colorectal, and/or pancreatic cancer.

The tumor total nutrient emulsion has the following advantages:

1. the crowd test is adopted to confirm that the product is the food with low glycemic index, and the results are more accurate and reliable instead of the methods of table look-up estimation, in-vitro digestion, animal test and the like.

2. By adopting the reasonable proportion of the carbohydrate and the dietary fiber, the energy supply requirement of tumor patients on the carbohydrate can be met, adverse reactions such as constipation and diarrhea can be reduced, and the glycemic index of the product can be more reasonably controlled.

3. Under the condition of combining abnormal energy consumption, abnormal carbohydrate metabolism, abnormal fat metabolism and abnormal protein and amino acid metabolism of a tumor patient in a specific disease state, the energy density of a product and the energy supply ratio of protein, fat and carbohydrate are in a reasonable proportion range, the gluconeogenesis is reduced, the insulin sensitivity is increased, the insulin resistance and the inflammatory response are reduced, and the method is more suitable for patients with insulin resistant tumors or cancers.

4. The product is in the form of emulsion, and can be taken without dissolving and opening the bag. Completely different from the dry mixing process of powder on the market, the uniformity, sense and microorganism of the product are more controllable.

5. The invention obtains the tumor full-nutrition emulsion with low glycemic index under the condition of adding carbohydrates with high glycemic index, such as maltodextrin, sucrose and isomaltose hypgather.

Drawings

FIG. 1: the preparation flow chart of the product.

FIG. 2: glucose and blood glucose response (mmol/L) of the tumor total nutrient formula of the special medical use of example 1.

FIG. 3: glucose and the area under the blood glucose curve of the tumor total nutrient formula for the specific medical use of example 1.

FIG. 4: insulin response (mIU/L) of glucose and the tumor total nutrient formula of the special medical use of example 1.

FIG. 5: glucose and the area under the insulin curve of the tumor total nutrient formula for the specific medical use of example 1.

Detailed Description

The invention relates to a tumor total nutrient emulsion, which adopts the reasonable proportion of carbohydrate and dietary fiber, can meet the energy supply requirement of tumor patients on carbohydrate, can reduce adverse reactions such as constipation, diarrhea and the like, and can more reasonably control the glycemic index of products.

The tumor total nutrient emulsion of the present invention may comprise carbohydrates, fats, proteins, dietary fibers, vitamins, minerals and additives.

In the tumor total nutrient emulsion herein, the content of carbohydrate may be 10.0-18.0 g/100mL, such as 11, 12, 13, 14, 15, 16 or 17g/100 mL. The carbohydrate may be one or more of maltodextrin, sucrose and isomalto-oligosaccharide. Preferably, the carbohydrate is maltodextrin.

In the tumor total nutrient emulsion herein, the content of fat may be 4-17 g/100mL, such as 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16g/100 mL. The fat may be one or more of corn oil, sunflower oil, canola oil, medium chain triglycerides and fish oil. Preferably, the fat is a mixture of sunflower oil, medium chain triglycerides and fish oil. In one embodiment, the weight ratio of sunflower oil, medium chain triglycerides and fish oil is 4-5:2.5-3.3:0.4-1, such as 4.7:2.9: 0.7.

In the tumor total nutrient emulsion, the content of the protein can be 7-13 g/100mL, such as 8, 9, 10, 11 or 12g/100 mL. The protein may be one or more of hydrolyzed soy protein, soy protein isolate, hydrolyzed whey protein, concentrated whey protein, sodium caseinate, and calcium caseinate. In one embodiment, the content of arginine in the protein is 580-1040 mg, the content of leucine in the protein is 600-1060 mg, the content of glutamic acid in the protein is 1600-2600 mg, and the content of essential amino acid in the protein is 3900-6370 mg per 100mL of the tumor total nutrient emulsion. The protein may be a composition of hydrolyzed soy protein and concentrated whey protein, such as a 9:1 to 18:1 composition of soy protein isolate and concentrated whey protein.

In the tumor total nutrient emulsion, the content of the dietary fiber can be 1.0-2.5 g/100mL, such as 1.5 or 2g/100 mL. In one embodiment, the ratio of carbohydrate to dietary fiber may range from 6:1 to 12:1, such as 7:1, 8:1, 9:1, 10:1, or 11: 1.

In the tumor total nutrient emulsions herein, the protein energy supply ratio may be 15% to 35%, e.g., 20% or 30%. The fat energy supply ratio may be 20% to 50%, for example 30%, 35%, 40% or 45%. The carbohydrate energy supply ratio may be 30% to 50%, for example 35%, 40% or 45%. The energy density may be 1.2 to 2.5kcal/mL, for example 1.5 to 2 kcal/mL.

The tumor total nutrient emulsion herein may further comprise 0.1-0.4g/100mL of vitamins. The vitamins are selected from vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, and vitamin B₁Vitamin B₂Vitamin B₆Vitamin B₁₂Nicotinic acid species, folic acid, pantothenic acid, biotin, and taurine. Preferably, vitamin a is selected from retinyl acetate, retinyl palmitate, beta-carotene and all-trans retinol. Preferably, the vitamin C is selected from the group consisting of L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, potassium L-ascorbate, and ascorbyl-6-palmitate. Preferably, vitamin D is selected from ergocalciferol and cholecalciferol. Preferably, the vitamin E is selected from the group consisting of d-alpha-tocopherol, dl-alpha-tocopherol, d-alpha-tocopherol acetate, dl-alpha-tocopherol acetate, mixed tocopherol concentrates, d-alpha-tocopherol succinate, and dl-alpha-tocopherol succinate. Preferably, vitamin B₁Selected from thiamine hydrochloride and thiamine nitrate. Preferably, vitamin B₂Selected from riboflavin and riboflavin-5' -sodium phosphate. Preferably, vitamin B₆Selected from pyridoxine hydrochloride and pyridoxal 5' -phosphate. Preferably, vitamin B₁₂Selected from cyanocobalamin, cyanocobalamin hydrochloride and hydroxocobalamin. Preferably, the nicotinic acid species is selected from nicotinic acid and nicotinamide. The vitamin A content may be 0.08-2.9mg/100 mL. The content of vitamin C can be 40-300mg/100 mL. Vitamin preparationThe content of D may be 0.002-2.7mg/100 mL. The vitamin E content may be 5.5-42mg/100 mL. Vitamin B₁The content of (B) may be 0.2-0.9mg/100 mL. Vitamin B₂The content of (B) may be 0.25-0.9mg/100 mL. Vitamin B₆The content of (B) may be 0.3-1.3mg/100 mL. Vitamin K₁Can be plant menadione. Vitamin K₁The content of (B) may be 0.01-0.05mg/100 mL. Vitamin B₁₂The content of (B) may be 0.001-0.006mg/100 mL. The content of nicotinic acid substances can be 2-7.2mg/100 mL. Preferably, the nicotinic acid species is selected from nicotinic acid and nicotinamide. The choline content may be 0.07-0.27g/100 mL. Preferably, the choline is selected from choline chloride and choline bitartrate. The taurine content may be 10-37mg/100 mL.

The tumor complete nutritional emulsion herein may further comprise 0.9-3.6g/100mL of mineral. The minerals may be selected from sodium, potassium, copper, magnesium, iron, zinc, manganese, calcium, phosphorus, iodine and selenium salts. Preferably, the sodium salt is selected from sodium bicarbonate, sodium dihydrogen phosphate, sodium citrate, sodium chloride and disodium hydrogen phosphate. Preferably, the potassium salt is selected from potassium gluconate, potassium citrate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate and potassium chloride. Preferably, the copper salt is selected from copper sulfate, copper gluconate, copper citrate and copper carbonate. Preferably, the magnesium salt is selected from magnesium sulfate, magnesium chloride, magnesium oxide, magnesium carbonate, magnesium hydrogen phosphate and magnesium gluconate. Preferably, the iron salt is selected from the group consisting of ferrous sulfate, ferrous gluconate, ferric ammonium citrate, ferrous fumarate, ferric citrate and ferric pyrophosphate. Preferably, the zinc salt is selected from zinc sulfate, zinc gluconate, zinc oxide, zinc lactate, zinc citrate, zinc chloride and zinc acetate. Preferably, the manganese salt is selected from manganese sulfate, manganese chloride, manganese carbonate, manganese citrate and manganese gluconate. Preferably, the calcium salt is selected from calcium carbonate, calcium gluconate, calcium citrate, calcium L-lactate, calcium hydrogen phosphate, calcium chloride, tricalcium phosphate, calcium glycerophosphate, calcium oxide and calcium sulfate. Preferably, the phosphorus salt is selected from tricalcium phosphate and calcium hydrogen phosphate. Preferably, the iodide salt is selected from the group consisting of potassium iodate, potassium iodide, and sodium iodide. Preferably, the selenium salt is selected from sodium selenate and sodium selenite.

The tumor total nutrient emulsion herein may further comprise 0.07-0.27g/100mL choline. The choline may be selected from choline chloride and choline bitartrate.

The tumor total nutrient emulsion herein may further comprise food additives, as necessary. For example, the food additive may be selected from sucralose, stabilizers, and flavors.

The invention also relates to a preparation method of the tumor total nutrient emulsion, which comprises the following steps:

(3) mineral packs were added followed by vitamin packs.

In addition, the invention also relates to the application of the tumor total nutrient emulsion in treating insulin resistant tumors, tumor complicated diabetes, non-diabetic stress hyperglycemia tumors or digestive tract tumors. For example, the tumor total nutrient emulsion can be prepared into food or medicinal compositions for patients suffering from insulin resistant tumors, tumors combined with diabetes, non-diabetic stress hyperglycemia tumors or digestive tract tumors.

Design of the product of the invention

The product of the invention is a tumor total nutrient emulsion which is designed by combining the nitrogen balance and the immune condition of tumor patients on the basis of the total nutrient formula of GB29922 special medical application formula food general rules and comparing the evaluation of the long-term administration safety, the nutrient sufficiency and the clinical effect of similar products at home and abroad. On the basis of the safety and nutritional sufficiency of the whole tumor nutrition, the invention reasonably mixes the carbohydrate, the dietary fiber, the protein, the fat, the vitamin and the mineral substance of the product, and requires the product to reach a low glycemic index by adjusting the reasonable energy supply ratio of the carbohydrate and the dietary fiber and sufficient protein and fat to reduce glycolysis of sugar under the conditions of high energy density of 1.5kcal/ml and addition of maltodextrin with a high glycemic index. The glycemic index of the product is determined by a crowd efficacy test, and the product is required to have a low glycemic index under the condition of a human body test and can be suitable for insulin-resistant tumor patients.

In the tumor total nutrient emulsion, the content of carbohydrate is within the range of 10.0-18.0 g/100 mL. Under the condition that the content of the carbohydrate is less than 10.0g/100mL, the energy supply ratio of the carbohydrate is insufficient, the gluconeogenesis phenomenon is obvious, and partial protein and fat are converted into glucose metabolism in vivo, so that the nutritional effect of a patient is poor after the patient takes the feed, and the blood protein, the immunity, the muscle health and the like are influenced. When the content of the carbohydrate is higher than 18.0g/100mL, the energy supply ratio of the carbohydrate is too high, the high content of maltodextrin influences the glycemic index of the product, the blood sugar load is aggravated, the infection risk caused by hyperglycemia is further increased, and the glycemic index of the product is too high to be taken by insulin-resistant tumor patients.

In the tumor total nutrient emulsion, the content of dietary fiber is within the range of 1.0-2.5 g/100 mL. Under the condition that the content of the dietary fiber is less than 1.0/100mL, the supply amount of the dietary fiber is insufficient, the daily dietary fiber requirement of a tumor patient cannot be met, the patient is easy to have the influences of constipation, gastrointestinal tract dyspepsia and the like, the blood sugar fluctuation range of the insulin resistant tumor patient is large, and the blood sugar cannot be well controlled. The content of the dietary fiber is higher than 2.5g/100mL, so that the content of the dietary fiber is too high, and adverse reactions such as abdominal distension, diarrhea, gas production and the like easily occur to patients, and the compliance of the patients is influenced.

In the tumor total nutrient emulsion, the ratio of carbohydrate to dietary fiber is 6: 1-12: 1. If the ratio of the carbohydrate to the dietary fiber is lower than 6:1, the content of the carbohydrate is lower, the content of the dietary fiber is higher, so that on one hand, the carbohydrate is insufficient in energy supply, the gluconeogenesis phenomenon is obvious, and the dietary fiber energy supply ratio is too high, so that the adverse reaction of abdominal distension and diarrhea of a patient is increased, and the compliance is influenced. If the ratio of carbohydrate to dietary fiber is higher than 12:1, the carbohydrate content is higher and the dietary fiber content is lower, which results in a higher glycemic index of the product, even a level of low glycemic index, which is not suitable for patients with insulin resistant tumors and limits the use of the product, as shown in table 1.

Table 1: amount and ratio of carbohydrates to dietary fiber

In the tumor total nutrient emulsion, the energy density of the product is 1.20-2.50 kcal/mL, and the energy source of the product is protein, fat and carbohydrate. The energy supply ratio of protein is 15-35%, the energy supply ratio of fat is 20-50%, and the energy supply ratio of carbohydrate is 30-50%.

If the energy density of the product is lower than 1.20kcal/mL, the nutrition intake of a patient in unit volume is insufficient, the water intake burden and the volume intake burden are increased, and the energy does not reach the standard, so that the further weight reduction of the patient is caused, and the administration effect of the patient is influenced. If the energy density of the product is higher than 2.50kcal/mL, the osmotic pressure of the product is high, the content is basically in a semisolid state, the nasal feeding or tube feeding is affected, and adverse reactions such as diarrhea, homeostasis disorder and the like easily occur to patients with high nutrition density.

If the energy supply ratio of the protein is less than 15%, the protein supply amount of the patient is insufficient, the effects of enhancing the muscle protein anabolism of the patient and relieving the inflammatory state cannot be achieved, and the increase of blood sugar after the product is taken cannot be delayed. If the energy supply ratio of the protein is higher than 35%, the load on the kidney of the patient is increased, gluconeogenesis is likely to occur, and the nutritional effect of the protein is reduced, and it is not suitable for patients with tumors having acute or chronic renal insufficiency.

If the energy supply ratio of the fat is lower than 20 percent, the fat of the patient is insufficient in energy supply, so that energy malnutrition is easy to occur, the inflammatory reaction and immune suppression of the patient are aggravated, and the patient is not suitable for the tumor patient with weight loss and insulin resistance. If the energy supply ratio of the fat is higher than 50%, the energy supply ratio of the fat is too high, gluconeogenesis phenomenon is obvious, the proportion of glycolipid is poor, nutrition is unbalanced, the taking effect of a patient is influenced, the product development difficulty is high, the taste is poor, the compliance of the patient is poor, obesity is easily caused, and the insulin resistance of the patient is aggravated.

If the energy supply ratio of the carbohydrate is lower than 30%, the carbohydrate of the patient is insufficient in energy supply, gluconeogenesis phenomenon is obvious, partial protein and fat are converted into glucose metabolism in vivo, and the immunity and muscle health of the patient are influenced. If the energy supply ratio of carbohydrate is higher than 50%, the glycemic index of the product is affected, the blood sugar load of the patient is increased, the infection risk caused by hyperglycemia is further increased, and the product is not beneficial to the administration of insulin resistant tumor patients, as shown in table 2.

Table 2: comparison of energy Density, protein energy supply ratio, fat energy supply ratio and carbohydrate energy supply ratio

In the tumor total nutrient emulsion, the content of protein is 8-13 g/100mL, the source of the protein is double protein, namely soybean protein isolate and concentrated whey protein, and the reasonable ratio of the two is 1: 5-18: 1. Therefore, every 100mL of the product contains 580-1040 mg of arginine, 600-1060 mg of leucine, 1600-2600 mg of glutamic acid and 3900-6370 mg of essential amino acid.

Table 3: partial amino acid content in whey protein and soybean protein

Protein source	Leucine	Essential amino acids	Glutamic acid	Arginine
					WheyProtein	111mg/g	484mg/g	204mg/g	25mg/g
Soy protein	78.1mg/g	494mg/g	204.7mg/g	79.1mg/g

If the protein content is less than 7g/100mL, the protein intake of the patient is insufficient, and malnutrition and cachexia are aggravated. If the protein content is higher than 13g/100mL, excessive protein intake is caused, which increases the burden of digestion and absorption, the burden of kidney function, and the like, which is not favorable for the recovery of patients.

The soybean protein isolate and the concentrated whey protein are both high-quality protein sources, and the animal and plant double proteins can be used for reasonably proportioning amino acids for enhancing immunoregulation, such as high arginine content and general leucine content of soybean protein, and high leucine content and low arginine content of whey protein. Therefore, the proportion of the soybean protein isolate and the concentrated whey protein is not in the range of 1: 5-18: 1, and the effects of reasonable proportioning and optimized effect cannot be achieved. In addition, the essential amino acid content is out of 3900-6370 mg, and a high-quality protein source cannot be guaranteed, or other amino acids are added. Arginine belongs to amino acid which is essential for the condition, and clinical tests clearly show that 0.5g/100kcal arginine can enhance the immunologic function of patients and reduce the incidence rate of postoperative infection, and the content of arginine is out of the range of 580-1040 mg, so that the effects of immunization and infection reduction are poor. Glutamic acid is a glutamine synthesis precursor, can improve nitrogen retention and relieve muscle protein degradation by synthesizing glutamine in vivo, and can play a role in improving the organism immunity of tumor patients and reducing infection risk by using 2500mg of glutamine every day. Therefore, the glutamic acid content is out of the range of 1600-2600 mg, which causes poor effects of immunization and infection risk reduction. Leucine and its metabolite can reduce decomposition of muscle protein and liver viscera protein, relieve dyscrasia and reduce loss of lean body mass. Leucine content outside the range of 600-1060 mg resulted in poor protein synthesis and negative nitrogen balance correction as shown in table 4.

Table 4: protein content and amino acid content

The invention further provides the following examples to facilitate an understanding of the invention. It is to be understood that the following examples are illustrative only and not limiting. The invention is limited only by the following claims.

Examples

Example 1: product preparation

Table 5: product formulation (in 100 mL)

Product energy: 250 ml/bottle 1573kJ (376kcal)

Energy density of the product: 1.50kcal/mL

Energy supply ratio of the product: protein 24%, fat 35%, carbohydrate 41%.

The tumor total nutrient emulsion of example 1 was prepared as the flow shown in fig. 1 and the formulation shown in table 5. Specifically, a protein powder and a part of maltodextrin were mixed, hydrated at 20Hz for 30 minutes, and treated in an emulsification tank at 45-50 ℃ to obtain a first fraction. Dissolving stabilizer and maltose at 50Hz for 15min, adding oleum Helianthi, medium chain triglyceride and fish oil, and dissolving at 50Hz for 10min to obtain second part. Mixing the first part and the second part, adding minerals and vitamins, dissolving at 50Hz for 10min, adding into a blending tank, treating at 55-60 deg.C, diluting to desired volume, measuring pH value, diluting to desired volume, preheating at 60-70 deg.C, homogenizing at 150-188bar, pasteurizing, cold storing at 20 deg.C for 10min, adding essence, homogenizing, and sterilizing.

Example 2: the crowd test proves that the tumor total nutrient emulsion is a low glycemic index food

1.1 sample size: 15 volunteers.

1.2 subject enrollment: selecting the subjects in the volunteer database, informing the time of the test and the types of the tested samples, inquiring whether the subjects participate in the test, signing the informed consent of the test after knowing the details of the test for the subjects meeting the enrollment standard, and entering the test formally when all the tests of the subjects are qualified before completing the enrollment.

1.3 inclusion criteria

15 healthy volunteers were collected. The following conditions are met:

(1) healthy adults aged 18-60 years, male and female; (2) normal body weight, BMI 18.50-23.9 kg/m²And without metabolic, digestive and endocrine disorders; (3) no history of diabetes, and no hypoglycemic agent; (4) no history of food allergy and intolerance, and no history of blood areola; (5) no medications affecting glucose tolerance are taken within nearly 3 months, such as vitamin and mineral supplements, oral contraceptives, acetylsalicylic acid, etc., steroids, protease inhibitors and antipsychotics; (6) a fasting of at least 10h can be tolerated.

Exclusion conditions: (1) special people, such as pregnant women and lactating women; (2) overweight and obese people; (3) metabolic diseases, digestive diseases or endocrine diseases; (4) (ii) has a history of diabetes or diabetes; (5) abnormal indexes of liver and kidney in physical examination; (6) history of food allergy, intolerance or blood fainting; (7) those with physical exertion and those with insufficient long-term sleep; (8) there was ingestion of drugs that affect glucose tolerance in approximately 3 months; (9) people who cannot tolerate 10h of food deprivation.

1.4 Subjects grouping

The study was planned to group 15 people, divided into three groups 1, 2, 3 according to the random control principle at a ratio of 1:2 (tumor total nutrient formula food for special medical use prepared in example 1: glucose), and received the corresponding test foods on the test day.

TABLE 6 study grouping

2 description of the food tested

Test food a: according to the detection result, the volunteer is required to take 50.00g of available carbohydrate, and then 416.6g of the tumor total-nutrient formula food with special medical application.

Reference food B: glucose, which is required to be ingested by each person at 50.00g of carbohydrate, is 55.0g of glucose.

3 test method

3.1 volunteer training and informed consent

Before the test, the volunteers are trained uniformly, the attention matters, the test arrangement, the volunteers' rights and possible hazards are explained, the volunteers are confirmed to know the relevant matters of the test and agree to participate in the test, and an informed consent is signed.

3.2 operating procedure

A uniform dinner was scheduled the day before the trial to control the intake of high protein, fat and dietary fibre food, and fasted for 14h before the trial and to avoid strenuous exercise, smoking, drinking. Walking to a laboratory in the early morning of the test day, sitting on a chair quietly for at least 5min, taking blood from fasting veins, orally taking reference food glucose and test sample tumor total nutrient formula food with special medical application, taking the food within 15min, recording the time of starting oral taking as 0min, and taking 3mL of blood from veins respectively 15min, 30min, 45min, 60min, 90min and 120min later. The blood sample is kept still for 30min, serum is centrifugally separated after 3000-10 min, the glucose level and the insulin level are respectively measured, and a gastrointestinal reaction record table is filled on the day after each blood sampling of a subject. The process is repeated every 7 days for 4 times, each volunteer should eat glucose 2 times, and the test sample should be taken for 1 time to obtain the tumor total-nutrient formula food with special medical application.

3.3 Observation of indicators

3.3.1 determination of serum glucose

Glucose oxidase method, Mirui BS-400 full-automatic biochemical analyzer, Zhongsheng company kit, and simultaneously performing quality control. The samples were completed by dean test, a third party clinical testing center.

3.3.2 determination of serum insulin

Radioimmunoassay, DPLGambyt CR10 radioimmunoassay produced in the United states, 135I radioimmunoassay, and quality control were performed in parallel. The samples were completed by dean test, a third party clinical testing center.

3.4 calculation method

3.4.1 calculation of GI

And (3) taking time as an abscissa and blood glucose values at all time points as an ordinate, preparing a blood glucose response curve, calculating the area under the blood glucose curve by adopting a Wolever method, and calculating the GI value of the tumor total nutrient formula food for special medical purposes by taking the GI of glucose as a reference food as 100.

GI value is equal to area under postprandial blood glucose curve of tumor total nutrient formula food/area under postprandial blood glucose curve x100

3.4.2 GL calculation

The available carbohydrate of the tumor total nutrient formula food for special medical application is 11.8g/100g, and the GL value of the tumor total nutrient formula food for special medical application is calculated.

GL value GI value/100 x CHO mass carbohydrate)

3.4.3 area ratio under insulin to blood glucose response Curve

And calculating the cumulative area ratio of the insulin to the blood sugar at each postprandial time point, and measuring the insulin sensitivity according to the area ratio of the insulin to the blood sugar response curve.

Area under curve of postprandial insulin of tumor total nutrient formula food for special medical application/area under curve of postprandial blood sugar of tumor total nutrient formula food for special medical application x100

3.5 statistical analysis

Using SPSS 18.0 software, blood glucose values and insulin values fit a normal distribution, passing

The data is described. Carrying out significance test by adopting t test, and taking alpha as 0.05 as a test significance level; when the blood sugar value and the insulin do not accord with normal distribution, a significance test is carried out by adopting a t' test, alpha is 0.05 as a test significance level, and the change of the area under a blood sugar curve, the area under an insulin curve and the accumulated area ratio of the insulin to the blood sugar at each time point is compared under the condition of taking glucose and the tumor total nutrient formula food with special medical application.

3.6 ethical evaluation

The study was approved by the ethical review committee of the chinese registered clinical trials, ethical review article No.: ChiECRCT 20190142.

3.7 adverse reaction management

The test process is monitored by doctors on site, and if the testee has adverse reactions such as nausea, vomiting, palpitation and the like, the adverse reactions can be timely treated.

4 results

4.1 volunteer basic situation description

16 volunteers, 12 females and 4 males aged 23-39 years and having a BMI of 18.6-23.9 g/m²Qualified physical examination, regular diet, no gastrointestinal diseases and administration of any medicine. Volunteers were trained and signed informed consent prior to the trial.

4.2 major Nutrition ingredients in the test food

As a result of physicochemical analysis performed by the inventors, it was found that 50.0g of carbohydrate was taken together with 55.0g of glucose; 416.6g of the tumor total nutrient formula food with special medical application is eaten, and 50.00g of carbohydrate, 22.6g of protein and 34.3g of fat are simultaneously ingested.

4.3 postprandial blood glucose response of tumor Total nutrient formula food for Special medical uses

The dynamic change of the postprandial blood sugar reflects the digestion and absorption state of exogenous test substances and the influence of food on the blood sugar.

4.3.1 blood glucose response curve of tumor Total nutrient formula food for Special medical applications

The blood sugar response curve is the visual expression of blood sugar response after eating certain food, and the blood sugar response curve is analyzed, the postprandial blood sugar fluctuation of the tumor total nutrient formula food with special medical application is obviously smaller than the blood sugar fluctuation of glucose, and the blood sugar fluctuation is specifically expressed in that the blood sugar is slowly increased and slowly decreased, so that the change of the postprandial blood sugar presents a relatively stable situation.

The blood glucose response curves of the two test substances are shown in fig. 2, and according to the blood glucose response curves, the blood glucose response curve of edible glucose rises within the first 30min and then continuously drops to the steady state of fasting blood glucose within 120 min; the blood sugar response curve of the tumor total nutrient formula food with special medical application is gradually increased within the first 30min and then decreased, and the overall fluctuation is obviously stable compared with the glucose.

According to the results of statistical analysis, the fasting blood glucose (0min) of both test subjects was within the normal range, and there was no statistical difference (P ═ 0.502).

From 15min to 90min after eating, the blood glucose value of a glucose group is obviously higher than that of a tumor total nutrient formula food group with special medical application, the statistical difference (P is less than 0.05) exists at five time points of 15min, 30min, 45min, 60min and 90min after eating, the glucose of a test object reaches a peak value at 30min, and the blood glucose response peak value of the tumor total nutrient formula food with special medical application at 30min is obviously lower than that of the glucose. Both subjects reached a plateau in fasting glucose at 120min with no statistical difference (P ═ 0.231).

4.3.2 area under blood glucose Curve of tumor Total nutrient formula food for Special medical application

The area under the blood glucose curve is a comprehensive index describing the response of the blood glucose response over a certain period of time. From the area analysis under the blood sugar curve, the blood sugar reaction caused by the tumor total nutrient formula food with special medical application is different from that caused by glucose, and the postprandial blood sugar change of the tumor total nutrient formula food with special medical application is obviously smaller than that of the glucose.

And respectively calculating the area under the blood glucose curve after the glucose is eaten and the tumor total nutrient formula food with special medical application by adopting a Wolever method. The area under the blood glucose curve is shown in figure 3. According to analysis, the area under the blood glucose curve after glucose intake is statistically different from the area under the blood glucose curve of the tumor total nutrient formula food for special medical application (P is less than 0.05) at 15min, 30min, 45min, 60min, 90min and 120 min. The blood sugar reaction is obviously different after the glucose is taken in and the tumor full-nutrition formula food with special medical application.

4.3.3 GI value of tumor Total nutrient formula food for Special medical application

The GI value of glucose is 100, and the GI value of the tumor total nutrient formula food for special medical use measured with glucose as a reference (area under the postprandial blood glucose curve of the tumor total nutrient formula food for special medical use/area under the postprandial blood glucose curve of glucose) × 100.

Calculating the area under the blood glucose curve of 2h after meal, and taking the average value after calculating each volunteer respectively, wherein the GI of the tumor total nutrient formula food with special medical application is 35.66 +/-9.21.

4.3.4 GL value of tumor total nutrient formula food for special medical use

Glycemic Load (GL) refers to the degree of glycemic response and insulin demand produced by a given amount of a food, which reflects both the quality and quantity of carbohydrates. Where the GL value is calculated in parts in order to let the consumer know the GI value of a food intake part. The packaging specification of the tumor total nutrient formula food for special medical application is 220ml, and in order to reflect the influence of eating one tumor total nutrient formula food for special medical application on the blood sugar of a human body, the method comprises the following steps of:

GL ═ GI × (mass taken in test food x% carbohydrate content in test food)/100

The total nutrient formula food for tumor with special medical application can utilize 11.8g/100g of carbohydrate, and GL is 9.27 when 220mL of carbohydrate is eaten each time. According to the GL division standard, GL of the tumor total nutrient formula food with special medical application is less than 10, so that the food belongs to low GL food.

4.4 postprandial insulin response

The secretion of insulin is divided into two parts, one part is insulin secreted to help maintain fasting euglycemia, called basal insulin, and the other part is insulin secreted to reduce postprandial blood glucose rise and maintain postprandial euglycemia, called prandial insulin. The secretion of prandial insulin controls the amplitude and duration of postprandial blood glucose elevation, and its main effect is to inhibit the production of endogenous glucose by the liver. Through the action mechanism, the blood sugar is maintained in a relatively stable state, and the damage to the blood vessel wall caused by overhigh fluctuation of the blood sugar is avoided.

4.4.1 tumor Total nutrient formula food insulin response Curve for Special medical applications

The insulin response curve is a visual representation of insulin response after eating a certain food. As can be seen from the insulin response curve (see fig. 4), both subjects also peaked at 30min and subsequently declined throughout the procedure. After 30min, the amplitude change of the insulin curve of glucose is obvious, and the postprandial insulin response curve of the tumor total nutrient formula food for special medical use is relatively gentle to the response curve of glucose insulin, which indicates that the amplitude change of the insulin is slow.

It can be found by analysis that both subjects fasting insulin (0min) are within the normal range, and there is no statistical difference between the three (P ═ 0.972). And the insulin response curve of the tumor total-nutrition formula food with special medical application at each time point has no significant difference (P is more than or equal to 0.05) compared with the glucose insulin response curve.

4.4.2 area under insulin Curve for tumor Total nutrient formula food for Special medical use

The area under the insulin curve is a comprehensive indicator describing the response of the insulin response over a certain period of time. The area under the insulin curve was also calculated using the Wolever method, using volunteers who were consistent with those who calculated the change in blood glucose. The area under the insulin curve at different time points is shown in figure 5 below.

In the insulin response of two tested foods, from 15min to 120min after meal, the area under the insulin response curve of the tumor total nutrient formula food for eating special medical application is smaller than the area under the insulin response curve of eating glucose and the area under the insulin response curve of control milk powder, and no statistical difference exists at each time point (P is more than or equal to 0.05). The insulin reaction after the glucose is taken in is not obviously different from that of the tumor full-nutrition formula food with special medical application.

5. Conclusion

According to an evaluation method and a program recommended by the Roche notation WS/T652-2019 food glycemic index, the change of blood sugar of healthy adult subjects eating the tumor total nutrient formula food with the special medical application within 2h is measured, the area under a blood sugar curve is calculated by adopting a Wolever method, the GI value of glucose is 100, and the GI value of the tumor total nutrient formula food with the special medical application is evaluated by the GI value of reference substance glucose.

The result shows that the GI value of the tumor total nutrient formula food for special medical application is 35.7 and the GL value is 9.27 by taking glucose as reference food (GI is calculated as 100). According to the grade division standard of the GI value, the tumor total nutrient formula food for special medical purposes has GI less than 55, and belongs to low GI food.

Example 3: clinical tests prove that the product is suitable for insulin resistant tumor patients

Advanced malignant tumors of the digestive system are easy to cause dysfunction of normal diet and nutrient absorption. The effective utilization of sugar in the body is difficult to realize in the intestine. Dysglycemia not only promotes cachexia of patients, but also causes disorder of acid-base balance, and endangers life of patients. The method takes an insulin-resistant digestive system malignant tumor late-stage patient as a research object, measures blood sugar value, fasting insulin, fasting lactic acid, insulin resistance index (HOMA2IR) and insulin secretion index (HOMA2 beta), and provides experimental basis for clinical nutrition treatment.

1 data and method

1.1 clinical data

90 hospitalized insulin-resistant digestive system malignant tumors (gastric cancer, colorectal cancer and pancreatic cancer) patients are selected, the inclusion standards simultaneously meet the digestive system malignant tumors and insulin resistance or diabetes diagnosis standards, the survival time is more than 3 months, and informed consent is signed. The test group and the control group are randomly divided into 45 cases.

1.2 methods

The experimental group started to use the insulin resistant tumor complete nutrient solution (the product of example 1) (energy density 1.5kcal/ml) 24h after surgical tumor resection, and the control group started to take the commercial enteral nutrition formulation "complete power" (energy density 1.0kcal/ml) 24h after surgical tumor resection. The two groups are both tube feeding, the adjustment is carried out 3 days before operation according to individual conditions of patients, 500 mL-1000 mL is carried out every day under the condition that the total amount of energy intake of the two groups is not changed, the required amount is reached on the 4 th day after operation, namely the experimental group tumor total nutrient solution is 1000mL every day, the control group can be 1500mL every day, and the maintenance is carried out for 3-8 days. The two groups of enteral nutrition infusion are matched with common insulin, the average dosage of the insulin on the 1 st day has no significant difference, the dosage of the insulin in the experimental group on the 2 nd and 3 rd days is reduced to 2/3 on the first day, and the dosage of the control group is still the same as that on the 1 st day.

1.3 Observation index

Observing the average value of blood sugar of 90 patients before tube feeding, on the 1 st day, the 2 th day and the 3 rd day after the operation; patient compliance; wound healing time after operation and hospitalization time after operation.

2. Results

Table 7: blood glucose value comparison of two groups of patients after tube feeding for 0 day, 1 day, 2 days and 3 days

Blood glucose values varied in both groups of patients on 0, 1, 2 and 3 days of tube feeding. Compared with a control group, the highest value, the lowest value and the average value of the blood sugar of the experimental group are obviously reduced after the experimental group is subjected to tube feeding for 1 day, the highest value and the average value of the blood sugar of the experimental group are obviously reduced after the experimental group is subjected to tube feeding for 2 days and 3 days, and the lowest value of the blood sugar has no obvious difference and can be related to the reduction of the insulin dosage.

Table 8: two groups of patients were gavaged for 0, 1, 2, 3 days for insulin resistance and insulin secretion index change

The average of the levels of insulin-fasting lactose, HOMA-IR, and HOMA-beta in the two groups of patients in the 0 sky belly of tube feeding was higher than that of the patients without insulin resistance tumor. Compared with a control group, after patients in an experimental group take the insulin resistance type tumor total nutrient solution for 1 day, 2 days and 3 days, the fasting insulin level is obviously increased, the fasting lactose is obviously reduced, the insulin resistance index HOMA-IR is obviously reduced, and the insulin secretion index is obviously increased. The insulin resistance level of a patient is obviously improved, the occurrence probability of complications is reduced, the experimental group can meet the energy requirement all day long by 1000mL each day, and compared with the full-capacity daily intake of 1500mL, the daily intake of the experimental group is beneficial to reducing the water intake burden of the patient and improving the compliance of the patient.

Example 4: clinical tests prove that the product is suitable for patients with tumor complicated with diabetes

Patients with gastrointestinal tumor complicated with diabetes tend to increase year by year, and are often accompanied with abnormal glucose, fat and protein metabolism in different degrees when being admitted, and some patients are also accompanied with serious complications. Stress conditions such as surgical wounds and postoperative infections can aggravate sugar metabolism disorder in vivo, the prognosis of patients is directly influenced, and timely nutrition support and blood sugar control after operation are particularly important for reducing the incidence rate of surgical complications and improving the curative effect. This study discusses a safe and effective method for controlling blood glucose in the post-operative Early Enteral Nutrition (EEN) process for patients with gastrointestinal tumors that are associated with diabetes.

1. Method of producing a composite material

1.1 80 cases of gastrointestinal tumors (gastric cancer, colorectal cancer or pancreatic cancer) combined with diabetes patients were selected and randomly divided into an experimental group (insulin resistant tumor complete nutrient solution, product component of example 1) and a control group (Yapeikai), and each group had 40 cases.

1.2 the experimental group started to apply the insulin resistant tumor complete nutrient solution 24h after the operation. The control group starts to take special preparation SR with good benefiting effect for diabetic intestinal (EN) 24h after operation, namely, every 100ml of warm boiled water is added with SR26g to prepare nutrient solution, wherein the nutrient solution comprises 93kcal of energy, 4.65g of protein, 12.29g of carbohydrate, 3.38g of fat and 0.76g of dietary fiber. The daily dosage of the two groups of patients is the same, the total amount is 500ml on day 1, and then the dosage is increased by 500-1000 ml every day until 1500ml/d, and the dosage is maintained for 4-6 d.

1.3 two groups of patients were blood glucose controlled by continuous intravenous infusion of insulin during the stress phase and subcutaneous injection of intermediate insulin during the stationary phase and measured before EN, on EN 5d and 8d morning post-surgery, respectively: nutrition evaluation indexes, namely weight (wt), Hemoglobin (HGB), serum albumin (Alb), Pre-albumin (Pre-Alb) and Transferrin (TF); ② the immune indexes, namely blood IgG, IgA and IgM. And meanwhile, postoperative complications such as infection of lung, wound and other parts, anastomotic leakage or stump leakage and the like are observed.

2. Results

2.1 clinical observations

None of the two groups died and had severe complications after surgery. During the treatment period, symptoms such as ketoacidosis, hyperosmolar coma, dehydration, hypoglycemia and the like do not appear at all.

2.2 glycemic control

In 30 cases (81.1%) of the group, the mean blood glucose was maintained at (7.8. + -. 1.1) mmol/L after lowering blood glucose by intravenous injection of insulin followed by subcutaneous injection during EEN. Only 2 cases of the experimental group have insulin resistance after operation, the blood sugar fluctuation is (11.2 +/-3.6) mmol/L, the maximum time of insulin is 7 days, and the average time is 5.5 days. In 7 cases of the control group, insulin resistance was observed after operation, blood glucose was fluctuated at (13.4 + -4.8) mmol/L, and intravenous drip of ordinary insulin was once added to insulin: 1u to 1g of sugar, the longest usage time was 9d, and the average was 7.4 d. With stable disease, the blood sugar is stabilized below 11.1mmol/L and then injected subcutaneously, 7 cases of blood sugar are controlled in the range of (7.9 +/-2.6) mmol/L until discharge, and the subcutaneous injection scheme is continued after discharge, or medication is guided by the outpatient department of diabetes.

2.3 laboratory index Change results

Table 9: laboratory index variation results

Denotes p <0.05

The weight and hemoglobin of two groups of patients were not changed significantly at 0, 5 and 8 days after the operation. The levels of serum albumin, pre-albumin and transferrin are obviously increased after the experimental group takes the tumor complete nutrient solution for 5 days; the immune indexes IgG, IgA and IgM level are also obviously increased. The control group has obvious effect only after 8 days of good effect, and has no obvious difference between serum albumin and transferrin in 5 days and 8 days; after the medicine is taken for 5 days, the immune indexes IgG, IgA and IgM level are also obviously increased, but the increasing effect is not as good as that of the experimental group.

Compared with the full-nutrition product with good proficiency for diabetes, the insulin-resistant tumor full-nutrition liquid applied to the patients with gastrointestinal tumor complicated with diabetes is more beneficial to controlling blood sugar, improving the nutritional status and the immune status of organisms, effectively reducing postoperative complications and promoting the patients to recover as soon as possible.

Example 5: clinical tests prove that the product is suitable for non-diabetic stress hyperglycemia tumor patients

After surgical operation, the body generates insulin resistance, can reduce the immunity of a patient, weaken the tissue repair capacity, influence the healing of wounds and increase the clinical death rate. In order to reduce insulin resistance after operation, the study observes the influence of the total nutrition of the early-stage tumor after operation on the insulin resistance of a patient with gastric cancer radical surgery with non-diabetic stress hyperglycemia.

1 object and method

1.1A total of 60 patients with non-diabetic gastric cancer were selected for hospitalization. All cases were operated in the same 1 operation group and underwent radical gastric cancer operation. No distant metastasis of liver, lung and the like is found before operation, no contraindication is caused by operation, and fasting blood sugar is in a normal range. All eligible patients were treated as 30 experimental groups and 30 control groups. The administration method is nasal feeding. The difference in sex, age, operation time, intraoperative hemorrhage volume, intraoperative blood transfusion volume, postoperative stage, pathological type and obesity case number of the patients in the two groups has no statistical significance (P is more than 0.05).

1.2 nutritional support protocol: patients in the experimental group are tube-fed with 0.9% sodium chloride injection 24h after operation, tube-fed with tumor total nutrient solution is started 48h, infusion is carried out at a constant speed continuously by using an infusion pump, the volume is gradually increased from 15ml/h to 50ml/h, and the total nutrient solution is changed into total enteral nutrition, namely the tumor total nutrient solution is 1000 ml/d and lasts for 4-5 d. The reference group is administered with an ampere nutrient solution with unknown glycemic index after surgery, the caloric requirement of the two groups reaches 25kcal/(kg d), and the total daily caloric value of the two groups of patients is consistent with the total infusion amount.

1.3 detection indexes: routine examination before operation and fasting blood sampling for blood sugar and serum insulin in early morning 48, 72 and 96 hours after operation. The insulin sensitivity is judged by adopting the reciprocal of the product of fasting blood glucose and fasting insulin to carry out quantitative calculation.

2. Results

2.1 comparison of fasting plasma glucose concentrations in two groups of patients is shown in Table 10.

Table 10: comparison of fasting plasma glucose in two groups of patients (mmol/L)

Group of	Number of	Before operation	48 hours after the operation	72 hours after operation	96 hours after operation
						Experimental group	30	5.16±0.12	14.50±1.20	10.9±1.82	6.60±0.61
Control group	30	5.23±0.15	14.40±1.19	12.40±1.14	9.73±0.92
						P		0.07	0.89	0.00	0.00

The differences in fasting plasma glucose concentrations between the preoperative groups were not statistically significant (P > 0.05). Fasting plasma glucose was higher than normal at 48 hours post-surgery in both groups, and the difference was not statistically significant between the two groups (P ═ 0.89). Compared with the 48 hours after operation, the blood sugar value of the control group is reduced by 13.9 percent at 72 hours after operation, the blood sugar value of the experimental group is reduced by 31.9 percent, and the difference between the two groups has statistical significance (P is 0.00); the mean blood glucose decreased 32.4% in the control group and 54.5% in the experimental group at 96 hours after surgery, and the difference between the two groups was statistically significant (P ═ 0.00).

2.1 comparison of serum insulin concentrations in two groups of patients is shown in Table 11.

TABLE 11 comparison of serum insulin concentrations (mU/L) in two groups of patients

The difference in serum insulin concentrations between the two groups of patients before surgery was not statistically significant (P > 0.05). The difference of serum insulin concentration at 48 hours after operation of two groups of patients has no statistical significance (P is 0.56), compared with the serum insulin concentration at 48 hours after operation, the difference of 72 hours after operation of a control group is reduced by 5.3 percent, the difference of an experimental group is reduced by 26.9 percent, and the difference between the two groups has statistical significance (P is 0.02); after surgery, the control group decreased by 25.6% at 96 hours, the experimental group decreased by 40.8%, and the difference between the two groups was statistically significant (P ═ 0.01).

2.3 comparison of insulin sensitivity in two groups of patients is shown in Table 12.

TABLE 12 comparison of serum insulin sensitivity in two groups of patients

Group of	Number of	48 hours after the operation	72 hours after operation	96 hours after operation
					Experimental group	30	3.43±0.34	6.24±0.09	12.70±0.23
Control group	30	3.31±0.25	4.11±0.16	6.67±0.35
					P		0.92	0.02	0.01

The difference between insulin sensitivity of the control group and the experimental group at 48 hours after the operation is not statistically significant (P is 0.92), compared with the control group at 72 hours after the operation, the difference between insulin sensitivity of the control group and insulin sensitivity of the experimental group is increased by 24.2 percent and the difference between insulin sensitivity of the experimental group and insulin sensitivity of the experimental group is increased by 81.9 percent, the difference between insulin sensitivity of the experimental group and insulin sensitivity of the experimental group is higher than that of the control group, and the difference between insulin sensitivity of the experimental group and insulin sensitivity of the experimental group is statistically significant (P is 0.02); after operation, the control group rises 101% at 96 hours, the experimental group rises 270%, and the difference between the two groups has statistical significance (P is 0.01).

The research shows that when the gastric cancer patient is administrated with the tumor complete nutrient solution in the early period after the operation, compared with the control group containing the ampelopsin, the blood sugar of the gastric cancer patient is reduced by 31.9% at 72 hours after the operation, but the blood sugar of the gastric cancer patient is reduced by 13.9% at 72 hours after the operation, the blood sugar of the gastric cancer patient is reduced by 54.5% at 96 hours after the operation, and the blood sugar of the gastric cancer patient is reduced by 32.4% at the control group. It is shown that the tumor total nutrient solution can reduce the blood sugar after operation in a certain time. In addition, compared with the serum insulin concentration value at 48 hours after operation, the control group at 72 hours after operation is reduced by 5.3 percent, while the experimental group is reduced by 26.9 percent; the control group is reduced by 25.6 percent at 96 hours after operation, while the experimental group is reduced by 40.8 percent, and the reduction of the experimental group is more obvious; indicating that the nutrition in the intestines can recover the postoperative insulin concentration in a certain time. The insulin sensitivity of the experimental group is better than that of the control group at 72 hours, 96 hours and 168 hours after the operation, which shows that the tumor complete nutrient solution can restore the insulin sensitivity of the patients within a certain time.

Example 6: clinical tests prove that the product is suitable for patients with digestive tract tumor

The influence of the tumor total nutrient solution on the nutritional status and the insulin resistance of patients with concurrent chemoradiotherapy of esophageal cancer is observed, and the supporting effect of nutritional intervention on patients with concurrent chemoradiotherapy of esophageal cancer is discussed.

1. Method of producing a composite material

120 screened patients with esophageal cancer without insulin resistance and hyperglycemia were divided into two groups at random after surgery: the control group is a conventional full nutrition group with unknown glycemic index, the experimental group is a tumor full nutrition liquid group with low glycemic index, and the conventional nutrition support and the tumor full nutrition support with low glycemic index are respectively implemented during the radiotherapy and chemotherapy. Comparing the nutritional status of the two groups of patients with the nutritional status of the patients after radiotherapy and chemotherapy, and detecting insulin resistance related indexes of the two groups of patients before radiotherapy and chemotherapy and 7d, 14d and 21d after radiotherapy and chemotherapy, including fasting blood glucose, fasting insulin, interleukin-6 and C-reactive protein.

2. Results

TABLE 13 comparison of nutritional status of patients with concurrent chemoradiotherapy of esophageal cancer in the conventional nutritional group and the complete nutritional liquid group

Before and after chemotherapy, the average body weight of the two groups is reduced, wherein the average weight of the conventional nutrition group is reduced by 11kg (P is less than 0.05); the constitutional indexes of the two groups are reduced, and the reduction trend of the conventional nutrition group is more obvious; the hemoglobin, serum albumin and white blood cell counts of the two groups are all reduced, and the reduction of the conventional nutrition group is more obvious.

TABLE 14 insulin resistance-related index changes for the regular nutrient group and the complete nutrient solution group

The differences in blood FBG, FINS, log-HOMA-IR, IL-6 and CRP values in the two groups of patients before chemotherapy were not statistically significant (P > 0.05). At 7d after chemotherapy, the levels of FINS, log-HOMA-IR and CRP in the tumor complete nutrition group were significantly lower than those in the conventional nutrition group (P < 0.05); 14d, tumor complete nutrition group FINS, log-HOMA-IR, IL-6 and CRP levels were significantly lower than the conventional nutrition group; at 21d, the tumor nutritionally complete group FBG, FINS, log-HOMA-IR, IL-6 and CRP levels were significantly lower than the conventional nutritional group.

3. Conclusion

The tumor total nutrient solution with low glycemic index can improve the nutritional state of patients with concurrent chemoradiotherapy of esophageal cancer, relieve the insulin resistance of the patients with esophageal cancer after operation, and is beneficial to relieving the stress reaction of organisms.

Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described above, and that various changes, substitutions, and alterations can be made without departing from the spirit and scope of the invention.

Claims

1. A full nutritional emulsion for tumor comprises 10-18 g/100mL carbohydrate, 4-17 g/100mL fat, 7-13 g/100mL protein and 1-2.5 g/100mL dietary fiber.

2. The tumor total nutrient emulsion according to claim 1, wherein the ratio of carbohydrate to dietary fiber is in the range of 6:1 to 12: 1.

3. The tumor total nutrient emulsion according to claim 1, wherein the tumor total nutrient emulsion has a protein supply ratio of 15% to 35%, a fat supply ratio of 20% to 50%, a carbohydrate supply ratio of 30% to 50%, and an energy density of 1.2 to 2.5 kcal/mL.

4. The tumor total nutrient emulsion according to claim 1, wherein the carbohydrate is selected from the group consisting of maltodextrin, sucrose and isomaltooligosaccharide.

5. The tumor total nutrient emulsion of claim 1, wherein the dietary fiber is a resistant dextrin.

6. The tumor total nutrient emulsion of claim 1, wherein the protein is selected from the group consisting of hydrolyzed soy protein, soy protein isolate, hydrolyzed whey protein, concentrated whey protein, sodium caseinate, and calcium caseinate.

7. The tumor total nutrient emulsion according to claim 6, wherein the protein has an arginine content of 580 to 1040mg, a leucine content of 600 to 1060mg, a glutamic acid content of 1600 to 2600mg, and an essential amino acid content of 3900 to 6370mg per 100mL of the tumor total nutrient emulsion.

8. The tumor total nutrient emulsion according to claim 6, wherein the protein is a 1:5 to 18:1 composition of soy protein isolate and whey protein concentrate.

9. The tumor complete nutritional emulsion according to claim 1, wherein the fat is selected from the group consisting of corn oil, sunflower oil, canola oil, medium chain triglycerides and fish oil.

10. The tumor total nutrient emulsion according to claim 1, wherein the osmotic pressure of the tumor total nutrient emulsion is 300-500msom/L, and the tumor total nutrient emulsion has a pH of 7.0-7.7.

11. The tumor total nutrient emulsion according to claim 1, comprising 0.1-0.4g/100mL of vitamins, 0.9-3.6g/100mL of minerals, 0.07-0.27g/100mL of choline and food additives.

12. The tumor total nutrient emulsion of claim 11, wherein the vitamin is selected from the group consisting of vitamin a, vitamin C, vitamin D, vitamin E, vitamin K₁Vitamin B₁Vitamin B₂Vitamin B₆Vitamin B₁₂Niacin, folic acid, pantothenic acid, biotin, and taurine;

preferably, the content of the vitamin A is 0.08-2.9mg/100 mL;

preferably, the content of the vitamin C is 40-300mg/100 mL;

preferably, the content of the vitamin D is 0.002-2.7mg/100 mL;

preferably, the content of the vitamin E is 5.5-42mg/100 mL;

preferably, vitamin K₁The content of (A) is 0.01-0.05mg/100 mL;

preferably, vitamin B₁The content of (A) is 0.2-0.9mg/100 mL;

preferably, vitamin B₂The content of (A) is 0.25-0.9mg/100 mL;

preferably, vitamin B₆The content of (A) is 0.3-1.3mg/100 mL;

preferably, vitamin B₁₂The content of (A) is 0.001-0.006mg/100 mL;

preferably, the content of the nicotinic acid substances is 2-7.2mg/100 mL;

preferably, the folic acid content is 0.03-0.13mg/100 mL;

preferably, the pantothenic acid content is from 0.97 to 3.88mg/100 mL;

preferably, the content of biotin is 0.01-0.03mg/100 mL;

preferably, the taurine content is 10-37mg/100 mL.

13. The tumor total nutrient emulsion of claim 12, wherein vitamin a is selected from the group consisting of retinyl acetate, retinyl palmitate, beta-carotene, and all-trans retinol;

preferably, the vitamin C is selected from the group consisting of L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate, potassium L-ascorbate, and ascorbyl-6-palmitate;

preferably, vitamin D is selected from ergocalciferol and cholecalciferol;

preferably, the vitamin E is selected from the group consisting of d-alpha-tocopherol, dl-alpha-tocopherol, d-alpha-tocopherol acetate, dl-alpha-tocopherol acetate, mixed tocopherol concentrates, d-alpha-tocopherol succinate, and dl-alpha-tocopherol succinate;

preferably, vitamin K₁Is plant menadione;

preferably, vitamin B₁Selected from thiamine hydrochloride and thiamine nitrate;

preferably, vitamin B₂Selected from riboflavin and riboflavin-5' -sodium phosphate;

preferably, vitamin B₆Selected from pyridoxine hydrochloride and pyridoxal 5' -phosphate;

preferably, vitamin B₁₂Selected from cyanocobalamin, cyanocobalamin hydrochloride and hydroxycobalamin;

preferably, the nicotinic acid species is selected from nicotinic acid and nicotinamide.

14. The tumor total nutrient emulsion of claim 11, wherein the choline is selected from the group consisting of choline chloride and choline bitartrate.

15. The tumor total nutrient emulsion of claim 11, wherein the minerals are selected from the group consisting of sodium, potassium, copper, magnesium, iron, zinc, manganese, calcium, phosphorus, iodine, and selenium salts;

preferably, the sodium salt is selected from sodium bicarbonate, sodium dihydrogen phosphate, sodium citrate, sodium chloride and disodium hydrogen phosphate;

preferably, the potassium salt is selected from potassium gluconate, potassium citrate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate and potassium chloride;

preferably, the copper salt is selected from copper sulfate, copper gluconate, copper citrate and copper carbonate;

preferably, the magnesium salt is selected from magnesium sulfate, magnesium chloride, magnesium oxide, magnesium carbonate, magnesium hydrogen phosphate and magnesium gluconate;

preferably, the iron salt is selected from the group consisting of ferrous sulfate, ferrous gluconate, ferric ammonium citrate, ferrous fumarate, ferric citrate and ferric pyrophosphate;

preferably, the zinc salt is selected from zinc sulfate, zinc gluconate, zinc oxide, zinc lactate, zinc citrate, zinc chloride and zinc acetate;

preferably, the manganese salt is selected from manganese sulfate, manganese chloride, manganese carbonate, manganese citrate and manganese gluconate;

preferably, the calcium salt is selected from calcium carbonate, calcium gluconate, calcium citrate, calcium-L-lactate, calcium hydrogen phosphate, calcium chloride, tricalcium phosphate, calcium glycerophosphate, calcium oxide and calcium sulfate;

preferably, the phosphorus salt is selected from tricalcium phosphate and calcium hydrogen phosphate;

preferably, the iodine salt is selected from potassium iodate, potassium iodide and sodium iodide;

preferably, the selenium salt is selected from sodium selenate and sodium selenite.

16. The tumor total nutrient emulsion as claimed in claim 15, which comprises 168-673mg/100mL sodium chloride and 114-456mg/100mL sodium citrate; 113-452mg/100mL potassium citrate and 249-998mg/100mL dipotassium hydrogen phosphate; 0.7-2.9mg/100mL copper sulfate; 71-285mg/100mL magnesium carbonate; ferric pyrophosphate of 3.8-15.5mg/100 mL; 1.5-6.4mg/100mL zinc sulfate; 0.7-3mg/100mL manganese sulfate; 120-484mg/100mL calcium carbonate; 56-227mg/100mL calcium hydrogen phosphate; potassium iodide 0.02-0.06mg/100 mL; and/or 0.01-0.06mg/100mL sodium selenite.

17. The tumor total nutrient emulsion according to claim 11, wherein the food additive is selected from the group consisting of sucralose, stabilizers, and flavors.

18. A method of preparing a tumor complete nutritional emulsion according to any one of claims 1 to 17 comprising:

(3) mineral packs were added followed by vitamin packs.

19. Use of the tumor complete nutritional emulsion according to any one of claims 1 to 17 for the preparation of a food composition for the treatment of insulin resistant tumors, tumor associated diabetes, non-diabetic stress hyperglycemic tumors, tumors of the digestive tract.

20. Use according to claim 19, wherein the tumour is oesophageal cancer, stomach cancer, large intestine cancer and/or pancreatic cancer.