NL2039331B1 - Composition containing akkermansia bacteria for moistening the intestines and promoting bowel movements and its use in constipation improvement - Google Patents

Abstract

The present invention discloses a composition for moistening the intestines and promoting 5 bowel movements, as well as its use in constipation improvement. The present invention belongs to the technical field of dietary nutritional supplements, and the composition contains a combination formula of okra, magnesium oxide, and Akkermansia muciniphi/a, and Akkermansia muciniphila can regulate the intestines and restore intestinal health. The composition does not contain any irritating laxative ingredients, can effectively assist in smooth and regular bowel 10 movements, and play a role in alleviating intestinal problems such as constipation, bloating, abdominal pain, diarrhoea, and increase the amount and volume of defaecation, soften stool, reduce the time required for defaecation, repair and lubricate the intestine, recover the intestinal barrier, increase beneficial bacteria, regulate the balance of intestinal flora, and has functions in terms of immunity, anti-inflammatory properties, and metabolism.

Description

COMPOSITION CONTAINING AKKERMANSIA BACTERIA FOR MOISTENING THE

INTESTINES AND PROMOTING BOWEL MOVEMENTS AND ITS USE IN CONSTIPATION

IMPROVEMENT

TECHNICAL FIELD

The present invention belongs to the field of dietary nutritional supplements and relates to a combination formula containing okra, magnesium oxide, and Akkermansia muciniphila. The composition does not contain irritating laxative ingredients, and is used for relieving intestinal problems such as constipation, bloating, abdominal pain, diarrhoea, etc.

BACKGROUND

Constipation refers to a decrease in the frequency of bowel movements or difficulty in defaecation, resulting in hard stools or a feeling of incomplete rectal emptying after defaecation, which affects people's quality of life. The best way to prevent constipation is to combine exercise, a high fibre diet, and adequate fluid intake. In addition, taking some dietary nutritional supplements has an effective effect on relieving constipation.

Okra (Latin name: Abelmoschus manihot (L.) Medik.), also known as Abelmoschus esculentus, and mucus is one of the important nutrients of okra, mainly a mixture of polysaccharides; the dietary fibre content of okra is 1.8 grams per 100 grams, which is twice that of Chinese cabbage; adequate mucus and dietary fibre can not only enhance satiety, but also promote gastrointestinal motility and prevent constipation.

In addition, the gut flora is the core part of the gut microbiota, and probiotics play a role in maintaining intestinal homeostasis and treating intestinal diseases. Intestinal probiotics adhere to the intestinal wall through adhesion, further colonize, and form a microbial film on the surface of the adhesive membrane to prevent the invasion of foreign bacteria and protect the health of the intestinal mucosa.

Akkermansia muciniphila (Akk muciniphila), a kind of intestinal beneficial bacteria, has significant anti-inflammatory effect, can repair the intestinal mucosal barrier, regulate the thickness of mucus, restore the intestinal barrier function, effectively inhibit the metabolic endotoxemia caused by the imbalance of intestinal flora, effectively reverse obesity and metabolic disorder caused by obesity and type 2 diabetes (T2D), and can also be used to reduce animal and human fat absorption, increase faecal excretion, and promote fat excretion or reduce visceral fat accumulation. Research has shown that Akk muciniphila can promote defaecation, fat excretion, reduce intestinal fat absorption, or decrease visceral fat accumulation.

Provide an effective dietary nutritional supplement, and the composition of the present invention can be used to effectively assist in smooth and regular bowel movements, and alleviate intestinal problems such as constipation, bloating, abdominal pain, diarrhoea, etc., which is a technical problem that needs to be solved.

SUMMARY

The purpose of the present invention is to, in response to the shortcomings of the prior art, provide a composition including okra, magnesium oxide, and Akkermansia muciniphila.

The content of okra in the present invention is 0.001 ~ 0.1 g/serving.

In further, the preparation method of okra includes the following steps: (1) wash, dry, and crush the okra; (2) add water, cellulase, and pectinase for enzymatic hydrolysis at a temperature of 50 - 55°C for 1 - 4 hours; (3) precipitate with anhydrous ethanol, and dry after filtration to prepare okra powder.

Further, the drying temperature in step (1) is 50 - 90°C, preferably 55 - 70°C. The drying time is 8 - 24 hours, preferably 10 - 14 hours.

Further, the amount of water added in step (2) is 10 - 100 times, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times.

Further, the amount of cellulase and pectinase added in step (2) is 5000-8000U/g, for example, 5000, 5500, 6000, 6500, 7000, 7500, or 8000U/g.

Further, the Akkermansia is an Akkermansia muciniphila pasteurized bacteria (Akk pasteurized bacterium).

Further, the Akk pasteurized bacterium has a bacterial mass greater than 1 billion

CFU/serving of the composition; preferably, greater than 2 billion CFU/serving of the composition; more preferably, greater than or equal to 5 billion CFU/serving of the composition.

Magnesium oxide, as a penetrant, can promote the entry of large amounts of water into the large intestine, softening and loosening stool. Excessive liquid causes the walls of the large intestine to stretch and stimulate contraction. The penetrating agent has the effect of clearing the intestine and eliminating intestinal endotoxins by promoting permeation and stimulating intestinal movement.

The content of magnesium oxide in the present invention is not less than 250 mg/serving, and preferably, not less than 350 mg/serving, and preferably, not less than 450 mg/serving.

In further, the composition further includes probiotics, wherein the probiotics are

Lactobacillus, Lactobacillus casei, Bifidobacterium, Lactobacillus, Lactobacillus acidophilus,

Bacillus licheniformis, Streptococcus faecalis, Bacillus subtilis, Lactobacillus butyricum,

Clostridium butyricum, and Akkermansia muciniphila, or a combination of two or more thereof.

The probictic of the present invention has a bacterial volume of not less than 1 billion

CFU/serving, preferably not less than 5 billion CFU/serving; preferably not less than 10 billion

CFU/serving.

In further, the composition includes other types of postbiotics.

The postbiotics of the present invention can be in the form of paste, suspension, emulsion, powder, particle, preferably in the form of powders.

Other types of postbiotics of the present invention further include Lactobacillus casei,

Plantarum plantarum, Bifidobacterium brevis, Streptococcus thermophilus, Bifidobacterium bifidum, Lactobacillus rhamnosus, r-aminobutyric acid, short chain fatty acids, tryptophan and combinations of two or more thereof.

The content of other types of postbiotics of the present invention is not less than 1 billion

CFU/serving of the composition, preferably, not less than 5 billion CFU/serving, and preferably, not less than 10 billion CFU/serving.

The content of probiotic and other types of postbiotics of the present invention is not less than 1 billion CFU/serving of the composition, preferably, not less than 5 billion CFU/serving, and preferably, not less than 10 billion CFU/serving.

In further, the composition includes polysaccharides.

The polysaccharides of the present invention are derived from extracts of okra, European mallow, hollyhock, Malva verticillata L, dandelion, Scutellaria baicalensis, Chrysanthemum,

Agaricus blazei, quinoa, jujube, apple, Auricularia auricula, ginseng, purple sweet potato, long skirt bamboo fungus, enoki mushrooms, goji berries, and Cordyceps militaris.

The content of polysaccharides in the present invention is not less than 1mg/serving, preferably, not less than 3 mg/serving and preferably, not less than 10 mg/serving.

Polysaccharides are widely present in the tissue cells of plants, animals, and microorganisms. Polysaccharides extract can lubricate the intestinal lining and repair intestinal epithelial cells, and can also regulate the richness of gut microbiota, increase the level of beneficial bacteria, and lower the pH value of the intestine.

Polysaccharide extracts can be obtained through water extraction, microwave extraction, enzymatic extraction, and ultrasonic extraction.

The composition of the present invention further includes plant extracts.

The plant extract of the present invention includes one or more of orange peel extract, fennel extract, clove extract, and liquorice extract.

The plant extract of the present invention is orange peel extract, fennel extract, clove extract, and liquorice extract.

In further, the polysaccharide and plant extract content of the present invention is not less than 1 mg/serving and preferably, not less than 1.5 mg/serving.

In further, the composition of the present invention does not contain stimulant laxatives. The stimulant laxative is fenofibrate, acetaminophen, anthraquinone or a combination of two or more thereof.

The stimulant laxative of the present invention is Aloe vera, senna leaves, rhubarb, bamboo leaves, cassia seeds, castor oil, phenolphthalein and a combination of two or more thereof.

Stimulant laxatives act on the enteric nervous system, and long-term use will easily lead to drug dependence, darkening the intestines and increasing the risk of colon cancer.

The products of the composition in the present invention can be in various dosage forms, including but not limited to common dosage forms of drugs, such as powder, suppository, gel, oral liquid, liquid preparation, capsule, soft capsule, powder, granule, tablet, and crystal balls, and can also be common dosage forms of health food and dietary supplement, such as tablet, hard capsule, soft capsule, beverage, solid drink, soft drink, dissolved beans, freeze-dried powder, milk beans, chocolate, sandwich soft candy, sandwich chocolate, tea drink, cold extracted coffee, and soft candy.

The various dosage forms of the product in the present invention for treating and/or improving intestinal health can be prepared according to conventional production methads for drugs, health foods, general foods, daily chemical products, feed, additives, etc. One or more carriers from the component can be mixed to prepare the desired dosage form.

Probiotics, as active microorganisms, can inhibit the proliferation of harmful bacteria, enhance the intestinal mucosal barrier, reduce intestinal inflammation, inhibit pathogenic bacterial activity, and regulate cell proliferation and apoptosis and other mechanisms to maintain gastrointestinal health, improve gut microbiota, and form a healthy gastrointestinal ecosystem.

Postbiotics, as an inanimate microorganism, mainly consists of inactivated bacterial cells, bacterial lysates, cell wall components, and metabolites. The beneficial metabolites of postbiotics, such as r-aminobutyric acid, short chain fatty acids, tryptophan, etc., are also components of the postbiotics, which maintain the integrity of intestinal barrier by regulating the gut microbiota.

The present invention provides a combination of okra, magnesium oxide, and Akkermansia for the preparation of a combination for relieving intestinal problems, such as bloating, abdominal pain, diarrhoea, constipation, irritable bowel syndrome, and inflammatory bowel disease.

The present invention provides a composition of okra, magnesium oxide, and Akkermansia muciniphila, and Akkermansia muciniphila can regulate the intestines and restore intestinal health. The composition does not contain any irritating laxative ingredients, can effectively assist in smooth and regular bowel movements, and play a role in alleviating intestinal problems such as constipation, bloating, abdominal pain, diarrhoea, and increase the amount and volume of defaecation, soften stool, reduce the time required for defaecation, repair and lubricate the intestine, recover the intestinal barrier, increase beneficial bacteria, regulate the balance of intestinal flora, and has functions in terms of immunity, anti-inflammatory properties, and metabolism.

The composition of the present invention can promote the first defaecation within 12 hours.

In further, the composition of the present invention can promote the first defaecation within 8 hours.

Explanation of terms

The term "Postbiotics" used herein refers to the beneficial components of probiotics after processing, including bacterial cells and metabolites.

The term "polysaccharide" used herein is composed of multiple monosaccharide molecules connected by glycosidic bonds, and is a class of complex and massive carbohydrate substances.

The term "extract" used herein refers to the product obtained by directing and concentrating the raw materials through physical and chemical extraction and separation processes.

DETAILED DESCRIPTION OF THE EMBODIMENTS

In order to facilitate the understanding of those skilled in the art, the present invention will be 5 further explained in conjunction with the embodiments below, and the contents mentioned in the embodiments are not limitation to the invention.

Example 1

A composition including magnesium oxide and Lactobacillus casei, wherein the magnesium content is 350 mg/serving, and Lactobacillus casei is an inactivated bacterium with bacterial volume of 1 billion CFU/serving.

Example 2

A composition including magnesium hydroxide and plant lactobacilli, wherein the magnesium content is 350 mg, and plant lactobacilli are inactivated bacteria with bacterial volume of 1 billion

CFU/serving.

Example 3

A composition including magnesium sulphate and Lactobacillus salivarius, wherein the magnesium content is 350 mg and Lactobacillus salivarius has a bacterial volume of 1 billion

CFU/serving.

Example 4

A composition including magnesium phosphate and Lactobacillus acidophilus, wherein the magnesium content is 350 mg and Lactobacillus acidophilus has a bacterial volume of 1 billion

CFU/serving.

Example 5

A composition including magnesium citrate and Bifidobacterium brevis, wherein the magnesium content is 350 mg and Bifidobacterium brevis has a bacterial volume of 1 billion

CFU/serving.

Example 6

A composition including magnesium carbonate and Streptococcus thermophilus, wherein the magnesium content is 350 mg and Streptococcus thermophilus has a bacterial volume of 1 billion

CFU/serving.

Example 7

A composition including magnesium chloride and Lactobacillus casei, wherein the magnesium content is 250 mg, Lactobacillus casei is an inactivated bacterium with a bacterial volume of 5 billion CFU/serving.

Example 8

A composition including magnesium threonate and Lactobacillus rhamnosus, wherein the magnesium content is 350 mg and Lactobacillus rhamnosus has a bacterial volume of 1 billion

CFU/serving.

Example 9

A composition including magnesium gluconate and Bifidobacterium bifidum, wherein the magnesium content is 350 mg and Bifidobacterium bifidum has a bacterial volume of 1 billion

CFU/serving.

Example 10

A composition including magnesium oxide and lactobacilli, wherein the magnesium content is 250 mg and lactobacilli have a bacterial volume of 5 billion CFU/serving.

Example 11

A composition including magnesium oxide and bifidobacteria, wherein the magnesium content is 250 mg and the bifidobacteria has a bacterial volume of 5 billion CFU/serving.

Example 12

A composition including magnesium oxide and Clostridium butyricum, wherein the magnesium content is 250 mg and Clostridium butyricum has a bacterial volume of 5 billion

CFU/serving.

Example 13

A composition including magnesium oxide and Akkermansia muciniphila, wherein the magnesium content is 250 mg and Akkermansia muciniphila has a bacterial volume of 5 billion

CFU/serving.

Example 14

A composition including magnesium oxide, Lactobacillus casei, and okra extract, wherein the magnesium content is 250 mg and Lactobacillus casei has a bacterial volume of 5 billion

CFU/serving.

Example 15

A composition including magnesium oxide, Lactobacillus casei, okra extract, and liquorice extract, wherein the magnesium content is 350 mg and Lactobacillus casei has a bacterial volume of 5 billion CFU/serving.

Example 16

A composition including magnesium oxide, Lactobacillus casei, Akkermansia muciniphila pasteurized bacteria (Akk pasteurized bacterium), okra extract, liquorice extract, orange peel extract, fennel extract, and clove extract, wherein the magnesium content is 250 mg and Akk

Pasteurella has a bacterial cell count of 5 billion cells per serving.

Example 17

A composition including magnesium oxide, Akkermansia muciniphila pasteurized bacteria (Akk pasteurized bacterium), okra extract, liquorice extract, orange peel extract, fennel extract, and clove extract, wherein the magnesium content is 350 mg and Akk pasteurization bacteria have a volume of 5 billion CFU/serving.

Example 18

A method for preparing a composition including magnesium oxide and Lactobacillus casei,

wherein the magnesium content is 450 mg, Lactobacillus casei is an inactivated bacterium with a bacterial volume of 5 billion CFU/serving. Crush magnesium oxide, Lactobacillus casei, and excipients separately, sieve, further mix, compress, and capsulate the mixture.

Example 19

A method for preparing a composition including magnesium oxide and Akkermansia muciniphila, wherein the magnesium content is 450 mg and Akkermansia muciniphila have a volume of 5 billion CFU/serving. Crush magnesium oxide, Akkermansia bacteria, and excipients separately, sieve, and further mix to obtain a uniformly mixed material for capsule filling, and then fill the capsule shell to obtain the capsules.

Example 20

A method for preparing a composition including magnesium oxide, Akkermansia muciniphila pasteurized bacteria (Akk pasteurized bacterium), okra extract, liquorice extract, orange peel extract, fennel extract, and clove extract. Crush, sieve, and further mix the composition and excipients separately, then compress and capsulate the mixture.

Example 21

A method for preparing a composition including magnesium oxide, Lactobacillus casei,

Akkermansia muciniphila pasteurized bacteria (Akk pasteurized bacterium), okra extract, liquorice extract, orange peel extract, fennel extract, and clove extract. Mix evenly the magnesium oxide,

Lactobacillus casei, Akk pasteurized bacteria, okra extract, liquorice extract, orange peel extract, fennel extract, and clove extract, spray the protective layer of plant materials outside the core of the mixture to form a buffer layer coating for wrapping protection, and finally mix with excipients to make a gel like material, which is then made into crystal balls through the pill making machine.

Example 22

Mouse experiment and experimental method: Administer 8mg/(kg-d) of loperamide to mice to induce constipation; 0.5 hours after the last administration, give mice with gastric lavage according to the above example, with a dose of 250mg/(kg-d), and record the first defaecation time, 24-hour faecal weight, and faecal moisture content.

First defaecation time: the time elapsed from the end of gastric lavage to the first defaecation;

Total weight of faeces: The total weight of faeces defecated by each mouse within 24 hours after gavage (calculated as the average value of mice in the group)

Faecal moisture content% = (wet weight of faeces - dry weight of faeces)/wet weight of faeces * 100%

The results are shown in table 1.

Table 1: Experiment on relieving animal constipation with the composition

First defaecation time Weight of Faecal moisture content

Constipation 427.5 £89.19 0.92 +£0.28 21.73 £6.19

Example 1 179.88 £67.28 1.78 £0.63 50.18 + 5.11

Example 2 186.82 + 66.29 1.94 £0.55 49.19 £6.27

Example 3 182.74 £68.91 1.91 £0.51 51.92 + 5.83

Example 4 186.98 + 70.19 1.83 £ 0.51 52.90 + 5.18

Example 5 185.17 £65.28 1.87 £0.62 48.12 +£4.75

Example 6 187.91 £64.37 2.20 +£0.68 57.81 £6.12

Example 7 191.99 + 67.28 1.99 + 0.67 55.27 £5.16

Example 8 181.81 £65.29 1.91 £0.56 52.91 £5.73

Example 9 177.29 £67.21 2.07 £0.55 51.82 £5.82

Example 10 288.67 + 70.19 2.28 £0.68 59.98 + 5.19

Example 11 290.98 + 68.18 2.37 £0.69 57.19 £5.92

Example 12 289.83 + 78.28 222+0.71 57.21 £5.76

Example 13 283.28 £71.92 2.31 £0.68 59.43 +£5.29

Example 14 278.63 £77.71 2.09 £0.57 60.19 £5.17

Example 15 191.27 £59.18 2.19 £0.58 60.25 £5.23

Example 16 149.88 + 58.17 2650.72 70.21 £6.16

Example 17 148.96 + 68.14 2.71 £0.66 70.34 £6.23

Example 18 156.19 + 60.18 2.51 £0.67 67.77 £6.17

Example 19 149.87 + 59.09 2.67 £0.68 69.65 +6.5

Example 20 148.61 + 56.18 2.74 £0.73 71.12 £5.19

Example 21 147.46 + 58.44 2.83 £0.52 72.11 £5.27

Table 1 reveals that after a combination of magnesium salts and probiotics is taken, the defaecation time was significantly improved, and the amount of faeces was increased to a certain extent, making the faeces softer and normalizing the water content of constipated mice faeces.

Example 23

Human trial: searched for 172 individuals (including 166 females and 6 males, without refractory or incurable population, and the statistics is not affected by individual differences) who had already experienced constipation. Volunteers consumed tablets containing the composition ofthe present invention daily (as in Example 20) and were observed changes in their bowel habits.

Efficacy evaluation:

Significant effect: The patients have shown significantly improved constipation symptoms, shortened interval between bowel movements, or improved stool quality, or smoother bowel movements, or increased frequency of bowel movements, or decreased toilet time. Other symptoms have also been significantly improved;

Invalid: The patients shown no changes in constipation symptoms.

Effective rate = Significant effect/Total number of samples;

The experimental results are shown in tables 2 and 3 below.

Table 2: Defaecation time after ingestion (h) (%)

Table 3: Defaecation sensation after ingestion

More relaxed, smooth and

FE on emptying and increased feeling of 33.72 intestinal emptying

As shown in tables 2 and 3, volunteers showed ideal therapeutic effects after ingesting the composition prepared according to the present invention, experienced defaecation within 8 hours and within 12 hours, and also have improved other symptoms significantly, including increased defaecation volume, increased defaecation volume, reduced toileting time, softened stool quality, and lubricated intestines.

Those skilled in the art will understand that, unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art. It should also be understood that terms, as defined in general dictionaries, should be interpreted to have meanings consistent with the context of the existing technology, and unless specifically defined herein, should not be interpreted with an idealized or overly formal meaning.

It should be appreciated that the detailed description of the technical scheme of the present invention with preferred embodiments is illustrative rather than restrictive. Those of ordinary skill in the art, based on reading this specification, can modify the technical schemes recorded in the various embodiments or make equivalent replacements for some technical features; such modifications or replacements do not depart from the spirit and scope of the technical schemes of the embodiments of the present invention.

Claims (10)

CONCLUSIONS 1. A composition for promoting bowel movements and treating constipation, comprising okra, magnesium oxide and Akkermansia muciniphila, the okra content being 0.001 - 0.1 g/serving; the Akkermansia muciniphila being a pasteurized Akkermansia muciniphila bacterium (Akk pasteurized bacterium) having a bacterial mass of more than 1 billion CFU/serving of the composition. The composition of claim 1, further comprising probiotics, wherein the probiotics are Lactobacillus, Lactobacillus casei, Bifidobacterium, Lactobacillus, Lactobacillus acidophilus, Bacillus licheniformis, Streptococcus faecalis, Bacillus subtilis, Lactobacillus butyricum, Clostridium butyricum, and Akkermansia muciniphila, or a combination of two or more thereof. The composition of claim 2, wherein the probiotic has a bacterial mass of more than 1 billion CFU/serving of the composition. The composition of claim 1, further comprising other types of postbiotics, wherein the other types of postbiotics comprise Lactobacillus casei, Plantarum plantarum, Bifidobacterium brevis, Streptococcus thermophilus, Bifidobacterium bifidum, Lactobacillus rhamnosus, r-aminobutyric acid, short chain fatty acids, tryptophan or a combination of two or more thereof. 5. The composition of claim 4, wherein other types of postbiotics have a bacterial mass of more than 1 billion CFU/serving of the composition. The composition of claim 1, further comprising polysaccharides derived from extracts of okra, Malva verticillata L, dandelion, Scuiellaria baicalensis, Chrysanthemum, Agaricus bisporus, quinoa, jujube, apple, Auricularia auricula, ginseng, purple sweet potato, long-stemmed bamboo mushroom, enoki mushrooms, goji berries, and Cordyceps militaris. The composition of claim 1, further comprising a plant extract, wherein the plant extract is one or more of orange peel extract, fennel extract, clove extract, and licorice extract. 8. The composition according to claim 1, other than stimulant laxatives, wherein the stimulant laxative is Aloe vera, Senna leaves, rhubarb, bamboo leaves, Cassia seeds, castor oil, phenolphthalein or a combination of two or more thereof. 9. Use of the composition according to any of claims 1 to 8 for effectively promoting smooth and regular bowel movements and for relieving intestinal problems such as constipation, bloating, abdominal pain and diarrhea. 10. A composition according to any one of claims 1 to 8, prepared as a soft capsule, liquid formulation, granule, powder, capsule, tablet or crystal spheres.