A composition for improving gastrointestinal function and preventing and treating constipation and its uses

Abstract

The present invention relates to a composition for significantly improving gastrointestinal function and preventing and treating constipation and its use. The composition contains soybean oligosaccharide and Jerusalem artichoke inulin. The research of the inventors shows that the composition of the present invention can effectively improve gastrointestinal function when applied to drugs or health products, and has a good effect of moistening the intestines and relieving constipation. The raw material composition of the present invention is simple, reasonable, the ingredients are natural, it is convenient to take, has high safety, no toxic and side effects, no adverse reactions, and will not produce dependence, and is suitable for constipation patients to take.

Description

[0001] This application is a divisional application of the application with the filing date of December 29, 2016, application number 201611242557.1, and invention title of "A Composition for Improving Gastrointestinal Function and Preventing and Treating Constipation". Technical Field

[0002] The present invention discloses a composition, in particular discloses a composition with soybean oligosaccharides and Jerusalem artichoke inulin as active ingredients. Further, the present invention discloses the application of the composition in improving gastrointestinal function and preventing and treating constipation. Background Art

[0003] Soybean oligosaccharides refer to the general term of oligosaccharides contained in soybeans, with a content of about 10%, mainly composed of sucrose, raffinose, stachyose, etc. Soybean oligosaccharides are widely distributed in plants, especially in leguminous plants. Most soybean oligosaccharides are extracted from the production of soybean protein whey. The whey contains various low-molecular proteins, polysaccharides, peptides, oligosaccharides, etc. Among them, carbohydrates account for about 62%, crude protein about 21%, ash 5%, and others 12%. And among the carbohydrates, the content of soybean oligosaccharides is relatively high. Currently, the methods for extracting soybean oligosaccharides from whey in China are: (1) ultrafiltration method; (2) membrane integration method; (3) microbial fermentation method; (4) alkali extraction method; (5) acid precipitation method; (6) microwave extraction method; (7) ultrasonic extraction method; (8) alcohol extraction method; (9) microwave and cellulase pretreatment extraction method, etc.

[0004] Soybean oligosaccharides are functional oligosaccharides composed of 2 - 10 identical or different monosaccharides bonded by glycosidic bonds, which cannot be a human nutrient source but have special physiological functions for the human body. It can promote the proliferation of the inherent beneficial bacteria - Bifidobacterium in the human intestine, inhibit the growth of putrefactive bacteria, and reduce the formation of toxic fermentation products. It is an important food base material; and the extraction of it solves the environmental protection problems of soybean protein production enterprises, so it has attracted much attention from countries around the world in recent years. In the late 1980s, Japan first initiated the research and development of the physiological functions of soybean oligosaccharides, and its developed soybean oligosaccharide products were launched on the market in 1998. So far, soybean oligosaccharides are the only functional oligosaccharides recognized by the US FDA for application in foods.

[0005] Inulin, also known as chicory root fiber, mainly consists of a class of structurally similar fructans. Inulin is one of the few soluble dietary fibers discovered so far. It is a proliferation factor for Bifidobacterium and Lactobacillus in the body. With characteristics such as low calorie, non-insulin dependence, and non-cariogenicity, it is widely used in the food fields of dairy products, bread, candies, beverages, and seasonings as a high-quality dietary fiber source and fat substitute. Numerous reports suggest that inulin has physiological activities such as improving the intestinal microenvironment, regulating blood lipids, preventing obesity, promoting mineral absorption, and vitamin metabolism.

[0006] Jerusalem artichoke, commonly known as sunroot, is a perennial herbaceous plant of the genus Helianthus in the Asteraceae family. Its tubers are rich in inulin. Jerusalem artichoke inulin is a linear biological polysaccharide formed by the connection of fructose molecules through glycosidic bonds, with a glucose molecule at the reducing end and a degree of polymerization of approximately 2 - 60. Existing literature reports that Jerusalem artichoke inulin can significantly reduce the blood glucose of STZ-induced type I diabetic rats. The mechanism may be to prevent the destruction of pancreatic islet β cells and increase insulin expression. The experimental results show that Jerusalem artichoke inulin has a good therapeutic effect on type I diabetes (Li Jihong, Wang Mi, Lin Shumei, et al. Study on the therapeutic effect of Jerusalem artichoke inulin on streptozotocin-induced type I diabetes in rats [J]. Modern Preventive Medicine, 2015, 42(16): 2997 - 3000). Lu Zheng et al. found that Jerusalem artichoke inulin has a certain protective effect on the oxidative damage of the kidneys and brain tissues of mice caused by alcohol (Lu Zheng, Zhang Jing, Gao Zhaolan, et al. Preventive and therapeutic effects of burdock inulin and Jerusalem artichoke inulin on chronic oxidative damage induced by alcohol in rats [J]. Food Science, 2010, 31(5): 270 - 273).

[0007] Constipation is one of the most common chronic digestive tract symptoms in clinical practice. Its incidence rate in China is approximately 10% - 15%, and the current number of constipated people has exceeded 130 million. Domestic constipation survey data shows that the incidence rate of constipation is related to factors such as age, gender, region, occupation, and educational level. With the improvement of people's living standards and the change of eating habits, the age of constipated patients is gradually getting younger, and the incidence rate of constipation in cities is much higher than that in rural areas. Research data shows that aging is a high-incidence factor for constipation, and the number of constipated patients increases significantly with age. Most epidemiological data believe that there is a close relationship between constipation and gender, and women are the high-risk group. The ratio of chronic constipation in the elderly over 60 years old in China is as high as 15% - 20%. A random, stratified, and graded survey of adults aged 18 - 70 in the Beijing area showed that the incidence rate of chronic constipation was 6.07%, and women were more than 4 times that of men, and mental factors were one of the high-risk factors. The incidence rate of constipation varies by region, and there are significant differences in the incidence rates between urban and rural populations.

[0008] Constipation is a painful and embarrassing condition. Most traditional constipation medications contain laxative ingredients, and long-term use can lead to strong dependence and subsequently secondary constipation. Therefore, such medications are not suitable for long-term use. Nowadays, people tend to choose products that are natural, green, have few side effects, and are effective. Summary of the Invention

[0009] The object of the present invention is to provide a composition, which comprises soybean oligosaccharide and Jerusalem artichoke inulin. At the same time, the present invention also discloses the application of this composition.

[0010] The applicant's research found that by combining soybean oligosaccharide and Jerusalem artichoke inulin, it has a synergistic and prominent effect on improving gastrointestinal function and preventing and treating constipation. Its long-term use safety and health care effect are superior to existing products. At the same time, the composition of the present invention has a synergistic therapeutic effect in preventing and treating constipation, and its curative effect is better than the sum of the two substances used alone. The composition of the present invention has high safety and is safe to take.

[0011] The present invention first introduces the combination of soybean oligosaccharide and Jerusalem artichoke inulin in this field for preventing and treating constipation. The applicant of the present invention first determined the feasibility of using the composition of soybean oligosaccharide and Jerusalem artichoke inulin for preventing and treating constipation through a large number of experimental studies.

[0012] The technical solution of the present invention provides a composition of soybean oligosaccharide and Jerusalem artichoke inulin, and the active ingredients soybean oligosaccharide and Jerusalem artichoke inulin have an obvious synergistic effect. When the composition of the present invention is used in pharmaceutical preparations, it can also selectively include pharmaceutically acceptable carriers. Correspondingly, the present invention provides the use of this composition for improving gastrointestinal function and preventing and treating constipation.

[0013] In the technical solution provided by the present invention, a preparation of the composition of the present invention is provided, which contains the composition of the present invention and a pharmaceutically acceptable carrier. The weight ratio of soybean oligosaccharide to Jerusalem artichoke inulin can be 0.01:1 - 20:1, preferably 0.11:1 - 10:1.

[0014] The composition of the present invention can be directly made into a preparation, or can be selectively added with a pharmaceutical carrier and then made into a preparation. The composition of the present invention has a positive effect on improving gastrointestinal function and preventing and treating constipation, so it can be applied to sub-healthy people as a health product. The health products mentioned in the present invention generally refer to products that can improve and protect the health status of the human body, including foods and beverages. The foods referred to include but are not limited to wheat products, starch products, meat products, plant extracts, milk, health sugars, etc.; the beverages referred to include all liquid products that can be drunk by the human body, including ordinary drinking beverages and functional beverages for improving specific functions.

[0015] When the present invention is applied to health care products, other nutrients can also be added when the product is finally prepared. These nutrients include starch, glucose, lactose, mannose, sucrose, syrup, honey, various amino acids, calcium, iron, zinc, vitamins, etc.

[0016] When the composition of the present invention is used in a specific application, it can be used in combination with auxiliary materials. The auxiliary materials can include excipients, antioxidants, pH regulators, preservatives, isotonic agents and any other auxiliary materials that are acceptable in pharmaceutical and nutritional aspects and have guaranteed safety.

[0017] The composition of the present invention can be prepared in various types, including capsules, tablets, powders, granules, oral liquids or syrups, etc., preferably powders and oral liquids. Changing the appearance of the product belongs to the technical solution that can be associated with those skilled in the art, so changing the shape of the final product belongs to the scope of the present invention. The applicant has studied the function of the product of the present invention and found that compared with the use of soybean oligosaccharides and Jerusalem artichoke inulin alone, the composition of the present invention can significantly promote the peristalsis of the intestines of constipation model mice and has a synergistic therapeutic effect. The composition of the present invention can significantly shorten the first defecation time of constipation model mice, increase the number and weight of defecation within 6 hours, and soften feces, and has a synergistic therapeutic effect.

[0018] The raw material composition of the invention is simple and reasonable, the ingredients are natural, the administration is convenient, the safety is high, there is no toxic side effect, no adverse reaction, and the efficacy of improving gastrointestinal function and moistening the intestine and facilitating bowel movements is achieved. DETAILED DESCRIPTION

[0019] The present invention is further described below by specific implementation methods, but the application scope of the present invention is not limited to the following embodiments. Within the content, spirit and / or scope of the present invention, the replacement and / or combination of the technical features of the present invention are obvious to those skilled in the art and are included in the present invention.

[0020] Preparation Example 1

[0021] The health care product provided in this embodiment is made of the following raw materials in percentage by weight: 75% soybean oligosaccharides and 25% Jerusalem artichoke inulin.

[0022] The health care product provided in this embodiment is a powder, and its preparation method comprises the following steps:

[0023] (1) Weigh soybean oligosaccharides and Jerusalem artichoke inulin according to the above weight percentages.

[0024] (2) Raw material pulverization: The raw material weighed in step (1) is pulverized, and then passed through an 80-mesh sieve, and the sieve residue is collected to obtain a powder.

[0025] Preparation Example 2

[0026] Soy oligosaccharides 100mg

[0027] Jerusalem artichoke inulin 10 mg

[0028] Mix the above components, grind them into powder, dissolve in deionized water to 1000 ml, seal, sterilize and subpackage to prepare oral liquid conforming to specific specifications.

[0029] In large-scale production, the oral liquid prepared by the present invention can be scaled up in dosage. After fully dissolving, it is canned and then sealed, sterilized and subpackaged into oral liquid conforming to specifications, such as 500 ml, 1 L, etc.

[0030] Preparation Example 3

[0031]

[0032] Stir and mix the above components into a composition, measure the weight and then make it into a powder.

[0033] Preparation Example 4

[0034]

[0035]

[0036] Stir and mix the above components into a composition, measure the weight and then make it into tablets.

[0037] Preparation Example 5

[0038]

[0039] Stir and mix the above components into a composition, measure the weight and then make it into capsules.

[0040] Preparation Example 6

[0041]

[0042] Preparation process: Add the prescribed amount of ethanol to soybean oligosaccharide and Jerusalem artichoke inulin, stir and dissolve, add injection water to 10 L, stir evenly, add 0.5% activated carbon for injection, stir and filter to remove carbon to obtain the injection.

[0043] Experimental Example 1 Study on the effect of the composition of the present invention on constipation model

[0044] 1. Mouse small intestine propulsion experiment

[0045] Take 70 healthy ICR mice, with 35 males and 35 females, weighing 18 - 22 g. Randomly divide them into 7 groups, with 10 mice in each group, namely normal control group, model control group, soybean oligosaccharide group, Jerusalem artichoke inulin group, soybean oligosaccharide-Jerusalem artichoke inulin composition A group, soybean oligosaccharide-Jerusalem artichoke inulin composition B group, and soybean oligosaccharide-Jerusalem artichoke inulin composition C group.

[0046] After fasting the mice for 12 h with free access to water, each dosing group except the normal control group was intragastrically administered loperamide hydrochloride (3.0 mg / kg), and the normal control group was given the corresponding volume of distilled water. After 30 min, each dose group was intragastrically administered the corresponding dose of the drug containing the ink suspension (100 mL of 2% ink + 1 g of sodium carboxymethylcellulose), and the normal control group and the model control group were given the corresponding volume of the ink suspension, and the intragastric administration volume was 0.2 mL / 10 g.

[0047] Drug administration in each group of animals:

[0048] Normal control group: Intragastrically administered an equal volume of distilled water

[0049] Model control group: Intragastrically administered an equal volume of distilled water

[0050] Soybean oligosaccharide group: Intragastrically administered 0.54 g / kg of soybean oligosaccharide

[0051] Jerusalem artichoke inulin group: Intragastrically administered 0.9 g / kg of Jerusalem artichoke inulin

[0052] Composition A group: Intragastrically administered 0.14 g / kg of soybean oligosaccharide + 1.3 g / kg of Jerusalem artichoke inulin

[0053] Composition B group: Intragastrically administered 0.54 g / kg of soybean oligosaccharide + 0.9 g / kg of Jerusalem artichoke inulin

[0054] Composition C group: Intragastrically administered 1.24 g / kg of soybean oligosaccharide + 0.2 g / kg of Jerusalem artichoke inulin

[0055] 30 min after drug administration, the mice were sacrificed by cervical dislocation, the abdominal cavity was opened to isolate the mesentery, and the intestinal tract from the upper end at the pylorus to the lower end at the ileocecal junction was excised. The length of the intestinal tract was measured as the "total small intestine length", and the distance from the pylorus to the advancing front of the carbon juice was measured as the "carbon juice advancing length", and the carbon juice advancing rate was calculated. Carbon juice advancing rate (%) = carbon juice advancing length (cm) / total small intestine length (cm) × 100.

[0056] 2. Mouse defecation experiment

[0057] Seventy healthy ICR mice, half male and half female, weighing 18 - 22 g, were randomly divided into 7 groups with 10 mice in each group, namely the normal control group, the model control group, the soybean oligosaccharide group, the Jerusalem artichoke inulin group, the soybean oligosaccharide - Jerusalem artichoke inulin composition A group, the soybean oligosaccharide - Jerusalem artichoke inulin composition B group, and the soybean oligosaccharide - Jerusalem artichoke inulin composition C group.

[0058] After mice were fasted overnight for 12 h (with unrestricted access to water), each dosing group except the normal control group was given loperamide hydrochloride (3.0 mg / kg) by gavage. The normal control group was given an equal volume of distilled water. 30 min later, each dose group was given the corresponding dose of drug containing the ink suspension by gavage, and the normal control group and the model control group were given the corresponding volume of ink suspension, and the gavage volume was 0.2 mL / 10 g for all groups.

[0059] Administration of drugs to each group of animals:

[0060] Normal control group: Given an equal volume of distilled water by gavage

[0061] Model control group: Given an equal volume of distilled water by gavage

[0062] Soybean oligosaccharide group: Given 0.54 g / kg soybean oligosaccharide by gavage

[0063] Jerusalem artichoke inulin group: Given 0.9 g / kg Jerusalem artichoke inulin by gavage

[0064] Composition A group: Given 0.14 g / kg soybean oligosaccharide + 1.3 g / kg Jerusalem artichoke inulin by gavage

[0065] Composition B group: Given 0.54 g / kg soybean oligosaccharide + 0.9 g / kg Jerusalem artichoke inulin by gavage

[0066] Composition C group: Given 1.24 g / kg soybean oligosaccharide + 0.2 g / kg Jerusalem artichoke inulin by gavage

[0067] After administration, starting from the time when the ink suspension was given, each mouse was individually placed in a mouse cage with compartments (the bottom of the cage was lined with absorbent paper), and the mice drank water and ate normally. The time for each mouse to excrete black feces for the first time, the number of defecations, the weight, and the fecal characteristics within 6 h were observed and recorded respectively.

[0068] 3. Data processing

[0069] The data were expressed as mean ± standard deviation and analyzed using SPSS 15.0 statistical software. The significance analysis of the differences between two groups was performed using two-tailed t-test.

[0070] 4. Experimental results

[0071] Table 1 Effects of the composition on the small intestine propulsion of constipated model mice

[0072]

[0073] Compared with the normal control group, ￥ p < 0.05, ￥￥ p < 0.01; compared with the model control group, ★ p < 0.05, ★★p < 0.01;

[0074] Compared with the soybean oligosaccharide group, # p < 0.05, ## p < 0.01; compared with the inulin from Jerusalem artichoke group, $ p < 0.05, $$ p < 0.01.

[0075] It can be seen from the results in Table 1 above that: (1) Compared with the model control group, the propulsion rate of carbon juice in the small intestine of each administration group was significantly increased.

[0076] (2) Compared with the administration of soybean oligosaccharide or inulin from Jerusalem artichoke alone, the propulsion rate of carbon juice in the composition group increased more significantly, and the composition group had a better effect on intestinal peristalsis, and the difference was statistically significant (P < 0.01). This indicates that the composition group of soybean oligosaccharide and inulin from Jerusalem artichoke can have a significant therapeutic effect on constipated mice, and the combination of the two has a synergistic effect.

[0077] Table 2 Effects of the composition on defecation of constipated model mice

[0078]

[0079]

[0080] Compared with the normal control group, ￥ p < 0.05, ￥￥ p < 0.01; compared with the model control group, ★ p < 0.05, ★★ p < 0.01;

[0081] Compared with the soybean oligosaccharide group, # p < 0.05, ## p < 0.01; compared with the inulin from Jerusalem artichoke group, $ p < 0.05, $$ p < 0.01.

[0082] It can be seen from the results in Table 2 above that: (1) Compared with the model control group, the first defecation time of each administration group was significantly shortened, and the defecation frequency and defecation weight were both significantly increased.

[0083] (2) Compared with the administration of soybean oligosaccharide or inulin from Jerusalem artichoke alone, the first defecation time in the composition group was shortened more significantly, and the defecation frequency and defecation weight increased more significantly, and the difference was statistically significant (P < 0.01). This indicates that the composition group of soybean oligosaccharide and inulin from Jerusalem artichoke can have a significant therapeutic effect on constipated mice, and the combination of the two has a synergistic effect.

[0084] Experimental Example 2 Efficacy test of the composition of the present invention

[0085] Clinical research was conducted on the preparation made in Example 4, and the report is as follows:

[0086] 1. Selection of Subjects

[0087] 1.1 Inclusion criteria for subjects:

[0088] a) Those with reduced bowel movement frequency and increased stool hardness;

[0089] b) Those with fewer than three bowel movements per week;

[0090] c) Those without organic constipation;

[0091] d) Those with habitual constipation;

[0092] 1.2 Exclusion criteria for subjects

[0093] a) Those who cannot eat orally or cannot take the test sample as required;

[0094] b) Those with unclear chief complaints;

[0095] c) Those who are too weak to conduct the experiment;

[0096] d) Those with constipation symptoms caused by surgical operations within 30 days;

[0097] e) Those with recent defecation difficulties caused by severe organic lesions (such as colon cancer, severe enteritis, intestinal obstruction, and inflammatory bowel disease, etc.)

[0098] f) Those with constipation difficulties accompanied by pain

[0099] g) Those who have had acute gastrointestinal diseases within 30 days;

[0100] h) Pregnant or menstruating women;

[0101] i) Those with severe systemic diseases involving the cardiovascular, liver, kidney, and hematopoietic systems, etc.;

[0102] j) Those with other concomitant diseases being treated;

[0103] k) Those who have taken items related to the test function in the short term, affecting the result judgment.

[0104] According to the above inclusion and exclusion criteria, 50 patients were selected, including 17 males and 33 females; the youngest age was 25 years old, the oldest was 85 years old, the shortest defecation time was 2.5 days, and the longest was 9 days; the shortest course of disease was 30 days, and the longest was 40 years.

[0105] 2. Experimental design, grouping, and data processing

[0106] A self - controlled experimental design before and after the test was adopted to compare the conditions before and after taking the drug. The data was... The paired t test was used for self-controlled trials.

[0107] Observation indicators: Perform blood, urine, feces routine examination and liver and kidney function test before treatment. Observe the changes in the number, duration, defecation situation and feces characteristics before and after medication.

[0108] The bowel movement condition was divided into grades I-IV according to the degree of difficulty in defecation (abdominal pain or anal burning sensation, discomfort, feeling of falling, whether there were frequent bowel movements but difficult and small bowel movements, etc.), and the integral value was calculated.

[0109] Grade Ⅰ (0 points): normal bowel movements;

[0110] Grade II (1 point): only a feeling of falling and discomfort;

[0111] Grade III (2 points): obvious discomfort during falling, or frequent but difficult defecation with small amount of stool, less abdominal pain or anal burning sensation;

[0112] Grade IV (3 points): Frequent abdominal pain or anal burning sensation;

[0113] Stool characteristics were classified into grades I-III according to the Bristol stool characteristics classification.

[0114] Grade Ⅰ (0 points): like sausage or snake, smooth and soft; with cracks on the surface but with obvious edges (easy to discharge);

[0115] Grade II (1 point): Sausage-shaped but with lumps; loose and lumpy, with rough edges, like muddy feces;

[0116] Grade III (2 points): Separate hard mass, like a fruit pit (not easy to expel).

[0117] 3. Treatment methods:

[0118] All patients took the preparation prepared in Example 4 of the present invention, 1 tablet each time, once a day, and stopped taking other laxatives. The dosage can be increased or decreased as appropriate according to the patient's physical condition and the improvement of constipation symptoms. The efficacy judgment criteria are as follows:

[0119] Clinical cure: dry and soft stools, one bowel movement per day, and all other symptoms disappear;

[0120] Marked effect: Constipation is significantly improved, stool quality is basically normal, the interval is 1 to 2 days, and 2 / 3 of other symptoms disappear;

[0121] Effective: The dry and hard stools are improved, the interval between bowel movements is shortened by 1 to 2 days, and other symptoms are improved to a certain extent;

[0122] Ineffective: No improvement in constipation or other symptoms.

[0123] 4. Results:

[0124] Subjective symptoms of the patients, such as abdominal distension, poor appetite, abdominal pain, dizziness, headache, bitter taste in the mouth, etc., were significantly improved. Compared with before treatment, after taking the drug, the defecation frequency of the patients increased significantly, the defecation duration shortened, and the degree of defecation difficulty and fecal characteristics improved significantly (Table 3). Among the 50 patients, 23 were cured, 16 showed marked improvement, 9 were effective, and 2 were ineffective, with a total effective rate of 96%.

[0125] Table 3 Changes in defecation and fecal characteristics of patients before and after continuous administration of the drug of the present invention for 14 days (n = 50)

[0126]

[0127] Compared with before use, *P < 0.001

[0128] The above clinical results indicate that the constipation symptoms of chronic constipation patients were significantly improved before and after medication (P < 0.001). The composition of the present invention can significantly increase the defecation frequency of chronic constipation patients, relieve the degree of defecation difficulty. After use, not only the defecation duration is significantly shortened, but also the fecal characteristics are significantly improved.

[0129] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A composition for improving gastrointestinal function and preventing and treating constipation, characterized in that, The composition consists of soybean oligosaccharide and Jerusalem artichoke inulin, and the weight ratio of soybean oligosaccharide to Jerusalem artichoke inulin in the composition is 0.6:

1.

2. A health care product preparation comprising the composition according to claim 1.

3. The health care product preparation according to claim 2, characterized in that, The health care product preparation contains or does not contain health care acceptable additives.

4. The health care product preparation according to any one of claims 2 to 3, characterized in that, The health care product preparation is selected from tablets, injections, pills, capsules, granules, powders, oral liquids or syrups.

5. The health care product preparation according to claim 4, characterized in that, The health care product preparation is powder or oral liquid.

6. Use of the composition according to claim 1 or the health care product preparation according to claims 2 to 4 in the preparation of a health care product for improving gastrointestinal function and preventing and treating constipation.

7. Use of the composition according to claim 1 or the health care product preparation according to claims 2 to 4 in the preparation of a health care product for improving defecation difficulty and / or in the preparation of a health care product for improving symptoms such as abdominal distension, poor appetite, abdominal pain, dizziness, headache and bitter taste accompanied by defecation difficulty.

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