A novel prebiotic composition for all-round prevention and treatment of metabolic syndrome and its preparation method

Abstract

The present invention relates to the field of pharmaceutical technology, and specifically to a novel prebiotic composition for all-round prevention and treatment of metabolic syndrome and a preparation method thereof. The composition comprises the following components: 2 to 8 parts of sweet tea, 1 to 5 parts of cassia seeds, 2 to 6 parts of mulberry leaves, 1 to 2 parts of roses, and 2 to 6 parts of lotus leaves. Each component works synergistically through the "monarch, minister, assistant and messenger" and can effectively act on all components of metabolic syndrome (hyperglycemia, obesity, fatty liver, etc.) at the same time, and each component can jointly regulate intestinal flora and its metabolites to exert its prebiotic effect, thereby achieving multi-target, all-round, and efficient comprehensive prevention and treatment of metabolic syndrome. In addition, its preparation method is simple and easy, the ingredients contained are safe and effective, and the taste is easily accepted by the public.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and specifically relates to a novel prebiotic composition for comprehensively preventing and treating metabolic syndrome and a preparation method thereof. Background Art

[0002] Metabolic syndrome (MS) is a pathological state caused by metabolic disorders of sugar, lipids, proteins and other substances in the body. It is a group of complex metabolic disorder syndromes, and its clinical features include obesity, atherosclerosis, dyslipidemia, hypertension, insulin resistance, impaired glucose tolerance, microalbuminuria, hyperuricemia and pro-inflammatory state (increased C-reactive protein). With the continuous improvement of living standards, metabolic syndrome has become a major public health issue worldwide. However, to date, there are no approved drugs for the overall treatment of MS in clinical practice; the treatment strategy is to use drugs separately for its individual symptoms, lacking a comprehensive intervention method with multiple targets and comprehensiveness, but the superposition of drugs often increases the side effects caused by treatment and increases the economic burden of the majority of patients. It can be seen that it is urgent to develop a safe, effective, affordable, highly accepted by the public and comprehensive new intervention method that can target all clinical characteristics.

[0003] Foods with medicinal and edible properties are widely promoted because they have the functions of conditioning, rehabilitation and health care, with few side effects, low cost and high public acceptance. In recent years, the preventive and therapeutic effects of Chinese medicinal materials with medicinal and edible properties on MS have gradually emerged, and they seem to have better potential for lowering blood sugar, regulating lipids and reducing weight than chemical synthetic drugs. In addition, since Chinese medicinal materials contain a variety of active ingredients, they can directly act on microorganisms in the intestine after taking them, increase beneficial bacteria and inhibit harmful bacteria. At present, many studies have shown that intestinal flora and its metabolites are closely related to the occurrence and development of MS. Therefore, regulating the structure of the flora and its metabolites is an important link for medicinal and edible foods to play a role. However, the corrective effect of a single medicinal and edible food on metabolic disorders is limited. It can often only improve a certain phenotype in metabolic syndrome and cannot act on multiple symptoms such as chronic inflammation, obesity, non-alcoholic fatty liver disease and insulin resistance at the same time. Formulating medicine is the key to solving this problem. The components in the formula work synergistically through the "monarch, minister, assistant and messenger" to play a greater role, but many current formulas are derived from medicines and cannot be eaten for a long time or have a poor taste. Therefore, the present invention selects medicinal ingredients with lipid-regulating, weight-reducing, blood sugar-lowering and anti-inflammatory potentials from Chinese medicinal and edible materials for combination and formulation to prepare a medicinal and edible preparation. The preparation not only achieves efficient and comprehensive prevention and treatment of MS by regulating the intestinal microenvironment, etc., but also has a good taste, can be taken for a long time, has good compliance, and truly achieves the accessibility, feasibility and safety of comprehensive prevention and treatment of MS. Summary of the invention

[0004] The present invention aims to solve the technical problems existing in the above-mentioned prior art. To this end, the present invention proposes a novel prebiotic composition for all-round prevention and treatment of metabolic syndrome and a preparation method thereof. The composition with prebiotic characteristics of the present invention, its components are all medicinal and edible ingredients, the preparation method is simple and easy, the taste is acceptable to the public, and it can be taken for a long time; in addition, the components in the composition work synergistically through the principle of "monarch, minister, assistant and envoy", jointly regulate intestinal flora and its metabolites, and can simultaneously target all components of metabolic syndrome (hyperglycemia, obesity, fatty liver, etc.) and chronic inflammation safely and effectively, thereby achieving all-round and efficient comprehensive prevention and treatment of metabolic syndrome and chronic inflammation.

[0005] In one aspect of the present invention, there is provided a composition having prebiotic properties, the composition comprising the following components:

[0006] 2-8 parts of sweet tea, 1-5 parts of cassia seeds, 2-6 parts of mulberry leaves, 1-2 parts of roses, and 2-6 parts of lotus leaves.

[0007] The composition of the present invention uses natural plant resources and Guangxi Zhuang Autonomous Region local specialty food sweet tea as the main raw materials, and is matched with Chinese medicinal ingredients that are both food and medicine announced by the National Health Commission: lotus leaf, mulberry leaf, cassia seed and rose. Each medicinal flavor is rich in a variety of active substances including polyphenols, caffeic acid, polysaccharides, etc., which are beneficial to the growth and reproduction of probiotics, thereby optimizing the intestinal microecology and improving host metabolic disorders. At the same time, the components in the preparation are strictly matched in accordance with the basic principle of "monarch, minister, assistant and messenger" in traditional Chinese medicine. The monarch drug sweet tea is sweet and cool in nature and has the effects of diuresis and swelling, promoting blood circulation and dispersing wind; the minister drug lotus leaf is sweet and warm in nature and has the effects of clearing away heat and dampness, and promoting the clear yang. The two are used together with warm and cool, and have the effects of diuresis and swelling, and removing dampness and promoting qi. The adjuvant mulberry leaf evacuates wind-heat, makes the clear yang rise, and enhances the effects of the monarch and minister drugs on diuresis and swelling, removing dampness and promoting qi. Cassia seed clears heat and soothes the liver, makes the liver qi smooth, and phlegm and dampness are transformed, and is an adjuvant with mulberry leaf. The rose flower is aromatic and dehumidifies, guides the medicine to the meridians, and dissolves phlegm and blood stasis in the body. The whole formula is rigorously compatible, and has the effects of diuresis, swelling, dehumidification and qi circulation, and is suitable for the treatment of metabolic syndrome and its complications; at the same time, due to the strict selection of the compatibility formula, the present invention has a good taste and is easy to be accepted by the public for long-term use.

[0008] In some embodiments of the present invention, the sweet tea is Rubus rubus, also known as sweet leaf Rubus rubus, which has the following advantages over other types of sweet plants such as monk fruit and stevia:

[0009] It has the best taste and is most easily accepted by the public. Its unique sweetness mainly comes from its unique ingredient, rubusoside, also known as sweetleaf rubusoside and rubusoside, which is 4% to 6% in sweet tea. The taste of rubusoside is similar to that of sucrose, and its sweetness is obviously superior among natural sweeteners, about 300 times that of sucrose, but its calorific value is only 1% of that of sucrose. At the same time, rubusoside has extremely high medicinal value and is the main active ingredient of sweet tea. At present, many studies have confirmed that rubusoside has the effects of lowering blood sugar, regulating lipids, reducing weight, lowering blood pressure and anti-inflammatory. In addition, some researchers have tested the antioxidant capacity of different types of tea drinks and found that the metal ion chelation effect of rubusoside sweet tea is significantly higher than that of other teas, which can interfere with the catalytic effect of metal ions in the lipid oxidation process and has excellent antioxidant effect.

[0010] However, at present, the main development and application direction of sweet tea is still limited to tea and sweetener. The present invention takes sweet tea, a local characteristic resource, as the main research object, explores and innovates its medicinal functions, and uses it as the main ingredient to develop a new type of medicinal and edible preparation with suitable taste and high safety, which can not only reduce weight, reduce fat and blood sugar, but also reduce C-reaction protein (CRP), reduce chronic inflammation of the body, and comprehensively prevent and treat metabolic syndrome. At the same time, it can also reduce the side effects of traditional drugs, which will provide a new direction for the development and utilization of sweet tea.

[0011] The composition of the present invention comprises 2 to 8 parts of sweet tea, 1 to 5 parts of cassia seeds, 2 to 6 parts of mulberry leaves, 1 to 2 parts of roses, and 2 to 6 parts of lotus leaves. This ratio range can ensure the prebiotic properties of the composition and the preventive and therapeutic effects on metabolic syndrome and its complications, and at the same time has the advantages of better taste and high patient acceptance. For example, the composition of the present invention comprises 2-6 parts of sweet tea, 1-4 parts of cassia seeds, 2-5 parts of mulberry leaves, 1 part of roses, and 2-5 parts of lotus leaves; or, 4-8 parts of sweet tea, 3-5 parts of cassia seeds, 4-6 parts of mulberry leaves, 1-2 parts of roses, and 4-6 parts of lotus leaves; or, 4-8 parts of sweet tea, 3-5 parts of cassia seeds, 4-6 parts of mulberry leaves, 1 part of roses, and 4-6 parts of lotus leaves; or, 5-7 parts of sweet tea, 3-5 parts of cassia seeds, 4-6 parts of mulberry leaves, 1 part of roses, and 4-6 parts of lotus leaves; or, 6 parts of sweet tea, 3-5 parts of cassia seeds, 4-6 parts of mulberry leaves, 1 part of roses, and 4-6 parts of lotus leaves; or, 6 parts of sweet tea, 4 parts of cassia seeds, 5 parts of mulberry leaves, 1 part of roses, and 5 parts of lotus leaves.

[0012] Another aspect of the present invention provides a method for preparing the above composition, comprising the following steps:

[0013] The components are mixed according to the proportion, extracted with water or an alcohol aqueous solution with a volume fraction of 20% to 30%, and dried to obtain the product.

[0014] Studies have shown that the higher the alcohol concentration, the more effective ingredients will be extracted, and the more toxic ingredients will be extracted. Therefore, in order to ensure the safety of the extract, the present invention uses water and low-concentration (volume fraction 20% to 30%) alcohol aqueous solution to extract the effective ingredients in the composition. The effective ingredients in the obtained water extract are mainly: saponins, glycosides, a small amount of flavonoids, a small amount of terpenes, tannins, and alkaloid salts. Using 20%-30% ethanol, the vast majority of active ingredients in Chinese medicinal materials can be extracted, mainly including: polyphenols, flavonoids, terpenes, and alkaloids.

[0015] In some embodiments of the invention, the alcohol is ethanol.

[0016] In some embodiments of the present invention, the extraction process is: adding 8 to 12 times the total mass of each component in amount of water each time, boiling at 95-100°C for 1 to 3 times, filtering, and combining the filtrate; or, adding 8 to 12 times the total mass of each component in amount of the alcohol aqueous solution each time, refluxing at 80-85°C for 1 to 3 times, filtering, and combining the filtrate.

[0017] In some embodiments of the present invention, the time of each decoction or reflux is 0.5 to 1.5 hours.

[0018] In some embodiments of the present invention, the filtering is performed using a 200-mesh filter.

[0019] In some embodiments of the present invention, the extraction process further comprises, after combining the filtrates, concentrating under reduced pressure to obtain a clear paste, and then vacuum drying the clear paste to obtain a dry paste.

[0020] In some embodiments of the present invention, the reduced pressure concentration is carried out at a temperature of 60° C. to 70° C. and under a pressure of -0.06 MPa to -0.08 MPa.

[0021] In some embodiments of the present invention, the relative density of the clear paste is 1.20-1.30 (measured at 60°C).

[0022] In some embodiments of the present invention, the vacuum drying is carried out at a temperature of 60° C. to 70° C. and under a pressure of -0.06 MPa to -0.08 MPa.

[0023] In some embodiments of the present invention, each 1 g of the dry paste is equivalent to 4-6 g of crude drug.

[0024] In another aspect, the present invention provides a preparation having prebiotic properties, wherein the preparation comprises the above-mentioned composition and auxiliary materials.

[0025] In some embodiments of the present invention, the amount of the composition (calculated as dry cream) in the unit dose of the preparation is 1 to 5 g, including but not limited to: 1 to 4.5 g, 1 to 4 g, 1 to 3 g, 1 to 2 g, 2 to 4.5 g, 2 to 4 g, 2 to 3 g, 4 to 5 g, 5 g, 4.5 g, 4 g, 2 g.

[0026] In some embodiments of the present invention, the auxiliary material includes at least one of a filler and an antioxidant.

[0027] In some embodiments of the present invention, the preparation includes the composition, a filler and an antioxidant, wherein the weight ratio of the composition (calculated as dry cream), the filler and the antioxidant is 1:0.05-0.2:2.5-3.

[0028] In some embodiments of the present invention, the preparation comprises the composition and an antioxidant, wherein the weight ratio of the composition (calculated as dry cream) to the antioxidant is 1:0.05-0.2.

[0029] In some embodiments of the invention, the filler comprises resistant dextrin.

[0030] In some embodiments of the present invention, the antioxidant includes at least one of vitamin C and grape seed extract.

[0031] In some embodiments of the present invention, the main component of the grape seed extract is proanthocyanidins; the grape seed extract can be extracted by a process commonly used in the art, for example, by crushing, warm soaking with 70% ethanol, filtering, concentrating under reduced pressure, and drying.

[0032] The auxiliary materials required by the present invention are simple, and only resistant dextrin, vitamin C and grape seed extract with antioxidant function are added. Resistant dextrin is a water-soluble dietary fiber. Compared with other auxiliary materials, taking resistant dextrin will not cause an increase in blood sugar, will not increase the metabolic burden of the body, and has the effects of regulating the intestines and delaying postprandial blood sugar. Currently, a variety of complex auxiliary materials are often added to the traditional Chinese medicine compound preparations on the market for flavor adjustment. The present invention only uses sweet tea for taste adjustment, which will not increase the metabolic burden of substances.

[0033] In some embodiments of the present invention, the preparation may further include oligofructose and erythritol.

[0034] In some embodiments of the present invention, the dosage form of the preparation is selected from powder, granules, pills, tablets, capsules, granules, and oral liquids.

[0035] The composition prepared by the present invention can be presented in the form of a dry paste, which can be further prepared into the above-mentioned various dosage forms through conventional preparation processes. For example, the preparation process of tablets may include the following steps: granulation: grinding the dry paste of the composition into powder, sieving, adding auxiliary agents, and mixing evenly to granulate; granulation: drying immediately after granulation, then granulation, screening and grading to obtain; tablet preparation: adding a lubricant after granulation and then tableting;

[0036] The preparation process of the capsule may include the following steps: grinding and sieving the dry paste of the composition, adding an appropriate amount of auxiliary materials, stirring and mixing evenly to obtain a capsule core material, and filling the material into an empty capsule shell to prepare a capsule preparation;

[0037] The preparation process of the oral liquid may include the following steps: mixing the dry paste of the composition, the auxiliary materials and the solvent in a certain proportion, and heating and stirring to fully dissolve the mixture;

[0038] The preparation process of the pills may include the following steps: sieving the ground dry paste powder of the composition and uniformly stirring and mixing it with the pre-dissolved matrix, preheating the pill dropping machine, dropping the mixture into a cooling oil column tube with a temperature gradient, taking out the condensed and formed small pills, centrifuging to remove the coolant on the surface of the small pills, and air-drying to obtain the pills.

[0039] The composition of the present invention can be further used to prepare preparations with various dosage forms, which is beneficial for patients to select dosage forms suitable for daily carrying and taking according to their own needs.

[0040] Another aspect of the present invention provides use of the above composition or the above preparation in preparing a medicament for promoting the growth or reproduction of Akkermansia muciniphila.

[0041] At present, most probiotic preparations have high storage conditions, and the separation and culture technology needs to be further improved. At the same time, there is a problem of high prices, so their application is often limited. In particular, Akkermansia muciniphila (A.muciniphila, AKK) is a strict anaerobic bacterium, and its storage and culture conditions are very strict. There is currently no bacterial preparation that directly supplements the AKK strain. The present invention screens and reorganizes the components in the composition through in vitro experiments, selects the best compatibility formula, and the five flavor components are reasonably compatible. The components complement each other and jointly promote the growth and reproduction of intestinal probiotics. In particular, the composition of the present invention can significantly increase the relative abundance of AKK bacteria. Compared with some products reported in the prior art, when taking the composition or preparation of the present invention, it is not necessary to supplement probiotics additionally, which has the advantages of safety, effectiveness, convenience in storage and transportation, and affordable price.

[0042] In some embodiments of the present invention, the medicament is used to increase the abundance of Akkermansia muciniphila in the intestine.

[0043] In some embodiments of the present invention, the medicament is used for preventing and / or treating metabolic syndrome and its complications.

[0044] Another aspect of the present invention provides use of the above-mentioned composition or preparation in the preparation of a medicament for preventing and / or treating metabolic syndrome and its complications.

[0045] MS is a group of diseases, whose clinical features include obesity, hyperglycemia (including diabetes or insulin resistance), hypertension, hyperlipidemia (including non-alcoholic fatty liver disease) and atherosclerosis. Currently, there is no single drug that can treat multiple symptoms of MS at the same time, so a combination of multiple drugs must be used for comprehensive prevention and treatment, but this will undoubtedly increase the medication burden on patients. In addition, MS is a disease that requires long-term treatment, so ensuring the safety of intervention measures is the focus of the current development of MS treatment drugs.

[0046] To solve the above problems, the inventor independently developed a new compound preparation. Compared with other compound preparations for the prevention and treatment of MS, the ingredients in the present invention are composed of food and food with medicinal and edible properties announced by the National Health Commission. These ingredients have conditioning, rehabilitation and health care effects, and are often mild in nature and taste, without obvious contraindications and cold and heat bias, good safety, suitable for long-term use, and more easily accepted by the public. Among them, sweet tea helps to control sugar and anti-inflammation, reduce fat and lose weight, lotus leaves help to reduce fat and lose weight, promote diuresis and reduce swelling, mulberry leaves help to reduce fat and lose weight, clear the liver and improve eyesight, roses help to resist oxygen and health care, promote qi and relieve depression, and cassia seeds help to lower blood pressure and regulate lipids, and moisturize the intestines and relieve constipation. The above five flavor ingredients can achieve a comprehensive prevention and treatment of "one drug with multiple targets" for all components of metabolic syndrome. After taking, they can also further play a corrective role in metabolic disorders by regulating intestinal flora and improving intestinal microenvironment. For example, it can not only reduce blood sugar, but also regulate blood lipids, reduce weight, control chronic inflammation of the body, and improve insulin resistance.

[0047] In some embodiments of the present invention, the metabolic syndrome and its complications are selected from the following conditions:

[0048] Obesity, dyslipidemia, non-alcoholic fatty liver disease, dysglycemia, hypertension, chronic inflammation, hyperuricemia.

[0049] In some embodiments of the present invention, the metabolic syndrome and its complications have disease manifestations or symptoms of obesity, dyslipidemia, dysglycemia, and chronic inflammation.

[0050] In some embodiments of the present invention, the drug is used to inhibit the increase of body fat percentage in metabolic syndrome and its complications.

[0051] In some embodiments of the present invention, the drug is used to inhibit lipid droplet accumulation.

[0052] In some embodiments of the present invention, the medicament is for improving glucose tolerance.

[0053] In some embodiments of the present invention, the drug is used to increase the sensitivity of peripheral tissues to insulin.

[0054] In some embodiments of the invention, the medicament is for reducing lipid deposition in the liver in metabolic syndrome and its complications.

[0055] In some embodiments of the present invention, the medicament is used to reduce the increase of uric acid caused by metabolic syndrome and its complications.

[0056] In some embodiments of the present invention, the medicament is used to improve chronic inflammation.

[0057] In some embodiments of the present invention, the drug is used to regulate the intestinal flora structure and flora metabolites.

[0058] In some embodiments of the present invention, the drug is used to reduce the ratio of Firmicutes to Bacteroidetes and the relative abundance of Firmicutes, and increase the relative abundance of Verrucomicrobia; preferably, the Verrucomicrobia include the genus Akkermansia.

[0059] In some embodiments of the present invention, the drug is used to reduce the content of branched-chain amino acid derivatives and phenylacetic acid in intestinal flora metabolites.

[0060] In some embodiments of the present invention, the unit dose of the composition (calculated as dry cream) is 1 to 5 g, including but not limited to: 1 to 4.5 g, 1 to 4 g, 1 to 3 g, 1 to 2 g, 2 to 4.5 g, 2 to 4 g, 2 to 3 g, 4 to 5 g, 5 g, 4.5 g, 4 g, 2 g; or, based on the composition, the amount of the composition (calculated as dry cream) in the unit dose of the preparation is 1 to 5 g, including but not limited to: 1 to 4.5 g, 1 to 4 g, 1 to 3 g, 1 to 2 g, 2 to 4.5 g, 2 to 4 g, 2 to 3 g, 4 to 5 g, 5 g, 4.5 g, 4 g, 2 g.

[0061] Another aspect of the present invention provides use of the above composition or the above preparation in the preparation of a medicament for preventing and / or treating chronic inflammation.

[0062] Sustained chronic inflammatory state is an important cause of the occurrence and development of MS. The composition or preparation of the present invention can improve chronic inflammation, further proving its comprehensive preventive and therapeutic effect on MS.

[0063] In some embodiments of the invention, the medicament reduces CRP levels.

[0064] In some embodiments of the present invention, the unit dose of the composition (calculated as dry cream) is 3 to 5 g, including but not limited to: 1 to 4.5 g, 1 to 4 g, 1 to 3 g, 1 to 2 g, 2 to 4.5 g, 2 to 4 g, 2 to 3 g, 4 to 5 g, 5 g, 4.5 g, 4 g, 2 g; or, based on the composition, the amount of the composition (calculated as dry cream) in the unit dose of the preparation is 3 to 5 g, including but not limited to: 1 to 4.5 g, 1 to 4 g, 1 to 3 g, 1 to 2 g, 2 to 4.5 g, 2 to 4 g, 2 to 3 g, 4 to 5 g, 5 g, 4.5 g, 4 g, 2 g.

[0065] According to the embodiments of the present invention, at least the following beneficial effects are achieved:

[0066] The present invention is based on the theory of traditional Chinese medicine, carries out scientific formulation and reasonable compatibility, carries out effective ingredients, preparation process, biological functions and clinical research, and develops a composition with clear ingredients, reasonable formula and clear functions for the comprehensive prevention and treatment of MS. The composition can achieve "one drug with multiple targets" for all components of metabolic syndrome, which can not only lower blood sugar, but also regulate blood lipids, reduce body weight, control chronic inflammation of the body, and improve insulin resistance. It can be used as a new prebiotic product for the comprehensive prevention and treatment of MS. After taking it, it can regulate intestinal flora and improve intestinal microenvironment, thereby exerting its effect of correcting metabolic disorders. In addition, since the present invention adds sweet tea as an important component of the composition, it is beneficial to increase sweetness, enrich the taste, and improve the public's acceptance, which is beneficial to the long-term prevention and treatment of MS. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] The present invention will be further described below in conjunction with the accompanying drawings and embodiments, wherein:

[0068] Figure 1 This is the growth result diagram of AKK bacteria cultured on plate culture medium for each formula.

[0069] Figure 2 Figure 2 shows the weight gain, body fat percentage and HE staining results of eWAT adipocytes in each group of mice.

[0070] Figure 3 The results of IPGTT, ITT, HOMA-IR, liver fat, blood uric acid, and serum C-reactive protein of each group of mice are shown in the figure.

[0071] Figure 4 This is the result of intestinal flora of mice in the model control group and the medium-dose group. DETAILED DESCRIPTION

[0072] The following will be combined with the embodiments to clearly and completely describe the concept of the present invention and the technical effects produced, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work are all within the scope of protection of the present invention.

[0073] The sweet tea in the following examples was purchased from Hunan Yijianing Technology Co., Ltd., and cassia seed, mulberry leaf, rose, lotus leaf, vitamin C and grape seed extract were purchased from Hunan Provincial Hospital of Traditional Chinese Medicine. All of the above medicinal materials have been certified by Hunan Institute of Traditional Chinese Medicine.

[0074] Example

[0075] Example 1

[0076] The present embodiment provides a composition with prebiotic properties, wherein the raw materials for preparing the composition are composed of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf, wherein the mass ratio of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf is 6:4:5:1:5.

[0077] This embodiment also provides a method for preparing the above composition, which comprises the following steps:

[0078] According to the formula, weigh the above five raw materials, add water at 100℃ and extract twice. For the first time, add 12 times the total weight of the raw materials, boil for 1 hour, and filter with a 200-mesh filter; for the second time, add 8 times the total weight of the raw materials, boil for 1 hour, and filter with a 200-mesh filter; combine the two filtrates. The filtrate is concentrated under reduced pressure (temperature 60-70℃, vacuum degree -0.06-0.08MPa) to a clear paste with a relative density of 1.20-1.30 (measured at 60℃); then vacuum dried (temperature 60-70℃, vacuum degree -0.06-0.08MPa) to obtain a dry paste.

[0079] Example 2

[0080] The present embodiment provides a composition with prebiotic properties, wherein the raw materials for preparing the composition are composed of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf, wherein the mass ratio of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf is 6:4:5:1:5.

[0081] This embodiment also provides a method for preparing the above composition, which comprises the following steps:

[0082] According to the formula, weigh the above five raw materials, add 30% ethanol and reflux at 85℃ to extract twice. In the first time, add 10 times the total weight of the raw materials, extract for 1 hour, and filter through a 200-mesh filter; the second time, add 8 times the total weight of the raw materials, extract for 1 hour, and filter through a 200-mesh filter; combine the two filtrates. The filtrate is concentrated under reduced pressure (temperature 60-70℃, vacuum degree -0.06-0.08MPa) to a clear paste with a relative density of about 1.20 (measured at 60℃), freeze-dried or vacuum-dried (temperature 60-70℃, vacuum degree -0.06-0.08MPa) to obtain a dry paste.

[0083] Comparative Example 1

[0084] This comparative example provides a composition with prebiotic properties, wherein the raw materials for preparing the composition consist of sweet tea, polygonatum odoratum and mulberry leaves, wherein the mass ratio of sweet tea, polygonatum odoratum and mulberry leaves is 1:1:1.

[0085] This comparative example also provides a method for preparing the above composition, which is carried out with reference to Comparative Example 1.

[0086] Comparative Example 2

[0087] This comparative example provides a composition with prebiotic properties, wherein the raw materials for preparing the composition consist of sweet tea, cassia seed and mulberry leaf, wherein the mass ratio of sweet tea, cassia seed and mulberry leaf is 1:1:1.

[0088] This comparative example also provides a method for preparing the above composition, which is carried out with reference to Comparative Example 1.

[0089] Comparative Example 3

[0090] This comparative example provides a composition with prebiotic properties, wherein the raw materials for preparing the composition consist of sweet tea, cassia seed, mulberry leaf and lotus leaf, wherein the mass ratio of sweet tea, cassia seed, mulberry leaf and lotus leaf is 1:1:1:1.

[0091] This comparative example also provides a method for preparing the above composition, which is carried out with reference to Comparative Example 1.

[0092] Comparative Example 4

[0093] This comparative example provides a composition with prebiotic properties, wherein the raw materials for preparing the composition consist of sweet tea, cassia seed, polygonatum, mulberry leaf and rose, wherein the mass ratio of sweet tea, cassia seed, polygonatum, mulberry leaf and rose is 1:1:1:1:1:1.

[0094] This comparative example also provides a method for preparing the above composition, which is carried out with reference to Comparative Example 1.

[0095] Comparative Example 5

[0096] This comparative example provides a composition with prebiotic properties, whose preparation raw materials are composed of burdock, cassia seed, lotus leaf, mulberry leaf, white kidney bean, hemp seed and stevia, wherein the mass ratio of burdock, cassia seed, lotus leaf, mulberry leaf, white kidney bean, hemp seed and stevia is 1:1:1:1:1:1:1:1.

[0097] This comparative example also provides a method for preparing the above composition, which is carried out with reference to Comparative Example 1.

[0098] Example 3

[0099] The present embodiment provides a composition with prebiotic properties, wherein the raw materials for preparing the composition are composed of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf, wherein the mass ratio of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf is 2:1:2:1:2.

[0100] This example also provides a method for preparing the above composition, which is carried out with reference to Example 1.

[0101] Example 4

[0102] The present embodiment provides a composition with prebiotic properties, wherein the raw materials for preparing the composition are composed of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf, wherein the mass ratio of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf is 4:1:2:1:2.

[0103] This example also provides a method for preparing the above composition, which is carried out with reference to Example 1.

[0104] Example 5

[0105] The present embodiment provides a composition with prebiotic properties, wherein the raw materials for preparing the composition are composed of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf, wherein the mass ratio of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf is 8:5:5:2:6.

[0106] This example also provides a method for preparing the above composition, which is carried out with reference to Example 1.

[0107] Example 6

[0108] The present embodiment provides a composition with prebiotic properties, wherein the raw materials for preparing the composition are composed of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf, wherein the mass ratio of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf is 4:3:3:1:4.

[0109] This example also provides a method for preparing the above composition, which is carried out with reference to Example 1.

[0110] Test Case

[0111] The present invention has carried out systematic experiments using the prebiotics prepared in the examples to intervene in model mice, and verified its effect of correcting metabolic disorders from the changes in mouse weight, blood sugar, liver fat, body inflammatory state, etc. In addition, the present invention performed 16S rRNA sequencing and non-targeted metabolomics analysis on mouse feces, and found that the preparation can be used as a prebiotic to regulate the structure of intestinal flora and its metabolites, improve the intestinal microenvironment and play its role.

[0112] Test Example 1

[0113] This test case investigated the effect of a combination of sweet tea, cassia seed, mulberry leaf, rose flower and lotus leaf on Akkermansia.

[0114] Akkermansia muciniphila is a beneficial bacterium that has been widely studied recently. Its abundance is negatively correlated with the risk of MS. A 1% increase in AKK can reduce the risk of MS by about 0.3%. Many studies have found that supplementing AKK can improve insulin sensitivity, lower blood lipids, prevent non-alcoholic fatty liver disease, and control chronic inflammation in the body. Therefore, increasing the relative abundance of AKK bacteria in the intestine is one of the important targets for treating metabolic syndrome.

[0115] Therefore, this test example investigated the effects of prebiotics with different compositions on AKK probiotics.

[0116] The specific method is as follows: preparation of drug-containing culture medium: Example 1: sweet tea 0.02g / ml, cassia seed 0.02g / ml, lotus leaf 0.02g / ml, mulberry leaf 0.02g / ml, rose 0.02g / ml; Comparative Example 1: sweet tea 0.02g / ml, polygonatum odoratum 0.02g / ml, mulberry leaf 0.02g / ml; Comparative Example 2: sweet tea 0.02g / ml, cassia seed 0.02g / ml, mulberry leaf 0.02g / ml; Comparative Example 3: sweet tea 0.02g / ml, cassia seed 0.0 2g / ml, mulberry leaf 0.02g / ml, lotus leaf 0.02g / ml; Comparative Example 4: sweet tea 0.02g / ml, cassia seed 0.02g / ml, polygonatum 0.02g / ml, mulberry leaf 0.02g / ml, rose 0.02g / ml; Comparative Example 5: burdock 0.02g / ml, cassia seed 0.02g / ml, lotus leaf 0.02g / ml, mulberry leaf 0.02g / ml, white kidney bean 0.02g / ml, hemp seed 0.02g / ml, stevia 0.02g / ml. The above medicinal materials decoctions were added to the liquid culture medium to prepare the drug-containing culture medium, and the control group was added with an equal volume of sterilized water. Thereafter, 1ml of AKK standard bacterial solution was inoculated into each test tube, placed in an anaerobic tank, and cultured at 37° for 48h. Thereafter, the bacterial solution in each test tube was diluted 2×10 -6 times, inoculate 200 μl of bacterial solution in each test tube onto three solid culture plates, and observe the number of colonies in each group after anaerobic culture for 72 h.

[0117] The test results are as follows Figure 1 As shown. Figure 1 It can be seen that compared with the control group, the number of AKK bacteria in each group increased after administration, among which the number of AKK bacteria increased most significantly after intervention in Example 1. Therefore, the components in the selected formula were sweet tea, cassia seed, mulberry leaf, rose and lotus leaf.

[0118] Test Example 2

[0119] This test example investigated the effect of the ratio of sweet tea, cassia seed, mulberry leaf, rose flower and lotus leaf on the taste.

[0120] The specific method is: prepare the prebiotic preparation with a ratio of 0.15g grape seed extract, 0.10g vitamin C and 5.75g resistant dextrin per 2g dry paste. Among them, resistant dextrin is the preferred prebiotic auxiliary material in the present invention, and it is combined with vitamin C and grape seed extract with antioxidant function to further improve the taste of the preparation.

[0121] A tasting panel of 15 people voted blindly to select the best taste. The taste evaluation results of the prebiotic preparations prepared in Examples 1 and 3-6 are shown in Table 1 below.

[0122] Table 1

[0123]

[0124]

[0125] It can be seen from the data in Table 1 that the ratio of sweet tea, cassia seed, mulberry leaf, rose and lotus leaf has a certain influence on the taste. The low ratio of sweet tea in Example 3 leads to a bitter taste, the high ratio of sweet tea in Example 4 leads to a sweet taste, and the inappropriate ratio of components in Examples 5 and 6 leads to a strong or tasteless taste of traditional Chinese medicine.

[0126] Test Example 3

[0127] This test example evaluated the efficacy of the composition of Example 1 on MS through animal experiments.

[0128] The specific methods used are as follows:

[0129] 1. Experimental animals: 50 5-week-old C57BL / 6J male mice weighing 20±2g were housed in the SPF animal room of the Second Xiangya Hospital of Central South University. The mice were given free access to food and water, and a 12 / 12h day and night cycle was ensured. After one week of adaptive feeding, they were used for subsequent animal experiments. The experimental protocol was reviewed and approved by the Animal Ethics Committee of the Second Xiangya Hospital of Central South University.

[0130] 2. Grouping and administration:

[0131] 2.1 Grouping: 8 mice were randomly selected as the normal control group and given a normal diet, and the rest of the mice were given a high-fat diet. After 14 weeks of high-fat intervention, the model was considered successful when the body weight was greater than 20% of the average body weight of the normal diet group. The 36 mice with successful modeling were divided into 4 groups according to body weight, with 9 mice in each group. The mice in the model control group were gavaged with sterile water, and the mice in the drug-treated group were gavaged with low, medium, and high concentrations (2, 4, and 6 times the recommended dose) of the preparations, respectively, and the gavage time lasted for 8 weeks.

[0132] 2.2 Administration: The proposed human dose is 4.5g per day (4g dry cream + 0.2g vitamin C + 0.3g grape seed extract). According to the dose conversion formula, the daily dry cream intake of mice is: 0.76g / kg. The three doses of low, medium and high are set at 2, 4 and 6 times the human intake, which are 1.5g / kg, 3.0g / kg and 4.5g / kg per day respectively. This preparation is dissolved in sterile water to prepare different concentrations, and 0.1ml / 10g of liquid is gavaged orally. The mice in the model control group are gavaged with the same volume of sterile water.

[0133] 3. Results Analysis

[0134] 1) Through high-fat feeding, the present invention successfully constructed an MS mouse model. Figure 2 It can be seen that after the compound preparation intervened in mice for 8 weeks, the weight gain of mice in each administration group was less than that of the model control group, among which the weight of mice in the medium dose group was lower than before, and there was a statistical difference compared with the model control group. Next, the present invention uses the mean value of the weight gain of the model control group as a reference, and the weight gain less than this value is considered effective. It is found that the weight loss efficiency of the medium dose group is as high as 88.9%, indicating that the medium dose is the best effective dose for the preparation to work (see Table 2).

[0135] Table 2 Weight loss efficiency of mice in each group

[0136]

[0137] Therefore, the present invention selected mice in the medium-dose group as representatives for small nuclear magnetic resonance, and found that the body fat rate of mice in the medium-dose group was significantly reduced compared with the model control group. Next, the present invention performed HE staining on the epididymal adipose tissue (Epididymal White Adipose tissue, eWAT) of each group of mice, and calculated the average fat cell area under different fields of view of each group of mice. The results showed that compared with the model control group, the eWAT area of ​​mice in each medication group was smaller than that of the model control group, indicating that the size of fat cells and lipid droplets were well controlled after the intervention of this formula.

[0138] In addition, the present invention also evaluates the improvement effect of the compound preparation on other metabolic disorders of MS except obesity. Figure 3It can be seen that the present invention conducted a glucose tolerance test (Intraperitoneal Glucose Tolerance Test, IPGTT) after 7 weeks of administration, and the area under the IPGTT curve of mice in each administration group was smaller than that of the model control group, indicating that the preparation can better protect pancreatic islet function and is not dose-dependent. After 8 weeks of administration, an insulin tolerance test (Insulin Tolerance Tests, ITT) was performed, and the area under the ITT curve of mice in each administration group was smaller than that of the model control group, indicating that the drug can increase the sensitivity of peripheral tissues to insulin, wherein the area under the curve of the medium-dose group and the area under the curve of the model control group are significantly different. Using an insulin detection kit to detect the fasting insulin level of mice and calculate the insulin resistance index (Homeostasis Model Assessment-Insulin Resistance, HOMA-IR) value, it was found that after 8 weeks of administration, the HOMA-IR of mice in each administration group had a downward trend relative to the model control group. Next, the present invention detects the content of triglyceride (TG) in the liver of each group of mice. The TG content in the liver of each administration group of mice is lower than that in the model control group, and the difference in TG content in the liver of the model control group and the low and high dose groups of mice is significant. The uric acid content in the serum of each group of mice was analyzed after 8 weeks of administration. The uric acid content in the serum of each administration group of mice was lower than that in the model control group, and the difference in the blood uric acid content between the high dose group of mice and the model control group of mice was significant. The content of CRP can often reflect the inflammatory state of the body, so the present invention detects the total CRP content in the serum of each group of mice and finds that the total CRP content in the serum of each administration group of mice is lower than that in the model control group, and the total CRP content in the serum of the high dose group of mice is significantly different from the total CRP content in the model control group. The above results suggest that the compound preparation has the effects of weight loss, improving glucose tolerance, improving insulin resistance, reducing lipid deposition in the liver, lowering uric acid and controlling chronic inflammation of the body.

[0139] 2) In order to explore the effect of the compound preparation on the intestinal flora structure of mice, the present invention performed 16S rRNA sequencing on the fresh feces of mice in the model control group, the medium dose group and the normal control group at 8 weeks after intervention. Figure 4It can be seen that the results of the principal component analysis (PCA) of β diversity showed good repeatability within the sample group, and good discrimination between groups, suggesting that the preparation can cause changes in the structure of the flora. At the phylum level, the intestinal flora of mice in the normal control group and the model control group were dominated by Firmicutes and Bacteroidetes, while the medium-dose group was dominated by Firmicutes, Bacteroidetes and Verrucomicrobia. The proportion of Firmicutes is higher in the feces of obese people, while the proportion of Bacteroidetes is higher in the feces of healthy people. Therefore, Firmicutes is often called "fat bacteria" and Bacteroidetes is called "thin bacteria". The compound preparation significantly reduced the ratio of Firmicutes to Bacteroidetes and the relative abundance of Firmicutes, and significantly increased the relative abundance of Verrucomicrobia, the phylum where AKK bacteria are located. Analyzing the species differences at the genus level, compared with the model control group mice, the preparation intervention changed the abundance of different genera in the intestinal microorganisms, significantly increased the relative abundance of the anti-inflammatory bacteria AKK by 39 times, and reduced the abundance of the pro-inflammatory bacteria Oscillibacter and Bilophila by 3 times, and reduced the key genus Desulfovibrionaceae of endotoxin production by 4 times. The present invention also detected metabolites in mouse feces, and the fecal metabolites of mice in the medium-dose group and the model control group were completely separated, indicating that the metabolic phenotypes between the two groups were significantly different. The differential metabolites between the two groups were screened by the standard of VIP≥1 and P≤0.05. The present invention found that the branched-chain amino acid derivatives in the feces of mice after administration were lower than those in the control group, and branched-chain amino acids were considered to be an indicator of insulin resistance. In addition, the metabolite phenylacetic acid that triggers liver fatty degeneration was reduced by 1.4 times after administration (Table 3). The above results suggest that the compound preparation can be used as a prebiotic to regulate the structure and metabolites of the intestinal flora, and play its role in correcting metabolic disorders.

[0140] Table 3 Differential metabolites in feces between the model control group and the medium dose group

[0141] Metabolites VIP Fold change Changing Trends Tryptophan-Leucine 1.04 0.50 (P＝0.04) His-Val 1.25 0.44 (P＝0.01) Phenylacetic acid 1.28 0.42 (P＝0.04)

[0142] Test Example 4

[0143] This test example evaluated the efficacy of the prebiotics in Example 1 on MS through clinical experiments.

[0144] The specific methods used are as follows:

[0145] 1. Treatment plan: Recruit patients with metabolic syndrome, and each person takes 8g of the compound preparation (2g of dry paste - equivalent to 10g of crude drug + 0.15g of grape seed extract + 0.10g of vitamin C + 5.75g of resistant dextrin) twice a day. The course of treatment is 3 months.

[0146] 2. Results Analysis

[0147] 2.1 Results Summary

[0148] A total of 23 subjects were included in this study, with an average age of 65±7 years old, including 7 males. Taking the compound preparation can significantly reduce the subjects' postprandial blood glucose and HbA1c compared with the baseline, and at the same time, blood lipids, blood pressure and blood uric acid levels are significantly improved compared with the baseline. It is worth mentioning that after drinking the compound preparation, the body's chronic inflammatory state is also well controlled. The present invention uses the baseline hs-CRP as a reference, and the reduction of hs-CRP after intervention compared with the baseline is considered effective. It was found that the anti-inflammatory efficacy of the preparation is as high as 74% (95% CI: 55%, 93%) (see Table 4).

[0149] Table 4 Comparison of blood glucose, blood lipids, blood pressure, uric acid and C-reactive protein at baseline and after taking the compound preparation for 3 months

[0150]

[0151]

[0152] 2.2 Preferred Embodiments

[0153] 1) Application Example 1: Li XX, male, 55 years old. Obese, with a history of diabetes and hypertension for more than ten years. After taking the compound preparation for 3 months, his weight decreased by 2.6kg, his systolic blood pressure decreased by 13mmHg, and his fasting blood sugar and glycosylated hemoglobin decreased from 6.26mmol / L and 6.8% before the intervention to 5.82mmol / L and 6.1%, respectively. Serum triglycerides decreased from 3.21mmol / L before the intervention to 2.33mmol / L. In addition, the chronic inflammatory state of the body was also well controlled, and hsCRP decreased from 5.57mg / L before the intervention to 3.44mg / L.

[0154] 2) Application Example 2: Liu XX, female, 75 years old, height 155cm, weight 62.4kg, with a history of hypertension. After taking the compound preparation for 3 months, the weight dropped to 56.25kg, and the blood lipid level was improved compared with the baseline. The serum triglyceride, cholesterol, and free fatty acid were reduced by 3.89mmol / L, 0.49mmol / L, and 0.34mmol / L respectively compared with before the intervention, and the high-density lipoprotein was increased. At the same time, the systolic blood pressure was reduced by 9mmHg compared with before.

[0155] 3) Application Example 3: Luo XX, female, 68 years old, pre-diabetic patient, with a history of hypertension. After taking the compound preparation for 3 months, her weight decreased by 1.4 kg, her systolic blood pressure decreased from 146 mmHg before intervention to 104 mmHg, her postprandial blood sugar decreased from 9.35 mmol / L before intervention to 7.59 mmol / L, and her serum triglyceride decreased from 2.13 mmol / L before intervention to 1.52 mmol / L.

[0156] The above clinical research results suggest that the compound preparation can improve various components of metabolic syndrome, and has the effects of weight loss, lipid regulation, blood pressure reduction, blood sugar reduction, uric acid reduction and controlling chronic inflammation of the body.

[0157] In general, in order to solve the problem of the current lack of comprehensive prevention and treatment methods for MS, the present invention has gone through a scientific and standardized assessment process for the specific indications of MS, and finally determined the various components, ratios, dosages and dosage forms. First, the present invention carefully selected several Chinese medicinal materials with lipid-lowering, weight-loss, sugar-control and anti-inflammatory potentials from the appendix of medicine and food homology, strictly followed the basic principle of "monarch, minister, assistant and messenger" in traditional Chinese medicine, and formulated them with sweet tea, and screened out the best prescription by co-cultivating with probiotics AKK. Secondly, in order to formulate the best compatibility ratio, the present invention used taste as a detection index, and repeatedly adjusted the content of each component, and screened out the most popular taste. Next, the present invention used different doses of compound preparations to intervene in mice, determined the best effective dose for the preparation to exert its therapeutic effect, and then carried out a small-scale human trial to track its clinical efficacy. Finally, the present invention selected a purification process that retained the effective ingredients of the compound to reduce toxicity components to the greatest extent, and developed the extract into a dosage form that is convenient for daily carrying and taking.

[0158] The embodiments of the present invention are described in detail above in conjunction with the embodiments, but the present invention is not limited to the above embodiments, and various changes can be made within the knowledge of ordinary technicians in the relevant technical field without departing from the purpose of the present invention. In addition, the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

Claims

1. A composition having prebiotic properties, characterized in that The active ingredients of the composition are composed of the following components: 2-8 parts of sweet tea, 1-5 parts of cassia seeds, 2-6 parts of mulberry leaves, 1-2 parts of roses, and 2-6 parts of lotus leaves; The prebiotic property is to promote the growth or reproduction of Akkermansia muciniphila; The composition is prepared by the following steps: The components are mixed according to the proportion, extracted with water or an alcohol aqueous solution with a volume fraction of 20%-30%, and dried to obtain the product; Wherein, the extraction process is: Add 8-12 times the total mass of each component in water each time, boil at 95-100℃ for 1-3 times, filter, and combine the filtrate; or, Each time, 8 to 12 times the total mass of each component is added into the alcohol aqueous solution, refluxed at 80 to 85° C. for 1 to 3 times, filtered, and the filtrate is combined.

2. The composition according to claim 1, characterized in that The decoction or reflux time for each time is 0.5~1.5h.

3. A preparation having prebiotic properties, characterized in that The preparation comprises the composition according to claim 1 or 2 and auxiliary materials.

4. The preparation according to claim 3, characterized in that The auxiliary material includes at least one of a filler and an antioxidant.

5. The preparation according to claim 4, characterized in that The filler includes resistant dextrin.

6. The preparation according to claim 4, characterized in that The antioxidant includes at least one of vitamin C and grape seed extract.

7. Use of the composition according to claim 1 or 2 or the preparation according to any one of claims 3 to 6 in the preparation of a medicament for preventing and / or treating metabolic syndrome and its complications; The metabolic syndrome and its complications are selected from the following conditions: Obesity, dyslipidemia, non-alcoholic fatty liver disease, dysglycemia, hypertension, chronic inflammation, hyperuricemia.

8. The use according to claim 7, characterized in that The medicament is used to increase the abundance of Akkermansia muciniphila in the intestine.

9. The use according to claim 7, characterized in that: The unit dose of the composition is 1-5 g.

10. The use according to claim 7, characterized in that Calculated on the basis of the composition, the amount of the composition in the unit dose of the preparation is 1 to 5 g.

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