High-absorptivity blood fat reducing composition containing burdock root aqueous extract as well as preparation method and application of high-absorptivity blood fat reducing composition

Abstract

The invention relates to a high-absorptivity blood fat reducing composition containing a burdock root water extract as well as a preparation method and application thereof, and relates to the field of preparation of blood fat reducing compositions. The blood fat reducing composition is prepared from burdock root aqueous extract, hawthorn flavone, cassia seed glycoside and phosphatidylcholine according to the mass ratio of (6 to 10): (1 to 2): (0.8 to 1.5): (0.5 to 1). According to the composition, the burdock root aqueous extract is taken as a core, hawthorn flavone, cassia seed glycoside and phosphatidylcholine are matched, and the problems of low absorption rate and single curative effect of the existing traditional Chinese medicine lipid-lowering medicine are solved through the dual design that active ingredients synergistically lower lipid and absorption-promoting ingredients improve bioavailability.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of blood lipid-lowering composition preparation, and particularly relates to a blood lipid-lowering composition containing arctium lappa root water extract with high absorption rate and a preparation method and application thereof. BACKGROUND

[0002] Hyperlipidemia refers to a metabolic disease of elevated total cholesterol (TC), triglyceride (TG) levels or reduced high-density lipoprotein cholesterol (HDL-C) levels in blood plasma, and is an important risk factor for atherosclerosis, coronary heart disease, stroke and other cardiovascular and cerebrovascular diseases. The incidence rate thereof is increasing year by year with the westernization of dietary structure and changes in lifestyle, and the patient population is gradually becoming younger.

[0003] At present, the drugs for clinically treating hyperlipidemia mainly include chemical drugs such as statins (e.g., atorvastatin) and fibrates (e.g., fenofibrate). Statin drugs reduce cholesterol synthesis by inhibiting HMG-CoA reductase, and have clear lipid-lowering effects, but long-term use can easily cause adverse reactions such as liver damage (elevated ALT and AST), muscle pain and rhabdomyolysis, and there is a "statin resistance" phenomenon for some patients. Fibrates can significantly reduce TG, but can cause gastrointestinal discomfort and kidney function damage. In addition, existing chemical drugs mainly target a single blood lipid index for regulation, are difficult to achieve multi-target point synergistic lipid-lowering, and have limited protective effects on vascular endothelium.

[0004] Traditional Chinese medicine has the advantages of "overall regulation and small side effects" in the treatment of hyperlipidemia. As a food and medicine homologous material, arctium lappa root is believed in traditional Chinese medicine to have the effects of moistening the intestines, relieving constipation and clearing heat and detoxifying. Modern pharmacological research has confirmed that arctium lappa root is rich in active ingredients such as polyphenols, dietary fiber and arctiin, and can play a preliminary lipid-lowering effect by adsorbing intestinal cholesterol and inhibiting lipase activity. However, the active ingredients of arctium lappa root are mostly polar or weakly polar substances, and the intestinal mucosa has poor permeability, so the bioavailability is less than 15% when used alone, which limits the lipid-lowering effect. At the same time, a single Chinese medicine component is difficult to cover multiple pathological links such as "cholesterol metabolism abnormality, triglyceride accumulation and lipoprotein transport disorder" of hyperlipidemia, and it is urgent to improve the absorption efficiency through multi-component synergistic compatibility to improve the therapeutic effect. SUMMARY

[0005] The present application aims to provide a blood lipid-lowering composition containing arctium lappa root water extract with high absorption rate and a preparation method and application thereof. The composition takes arctium lappa root water extract as the core, and is matched with hawthorn flavones, cassia seed glycosides and phosphatidylcholine. Through the dual design of active ingredient synergistic lipid-lowering and absorption-promoting ingredient improving bioavailability, the problems of low absorption rate and single efficacy of existing Chinese medicine lipid-lowering drugs are solved.

[0006] In a first aspect, the present application provides a high-absorption-rate lipid-lowering composition containing Arctium lappa L. water extract, which comprises Arctium lappa L. water extract, hawthorn flavones, cassia seed glycosides and phosphatidylcholine in a mass ratio of (6-10):(1-2):(0.8-1.5):(0.5-1).

[0007] Further, the mass ratio of the Arctium lappa L. water extract, hawthorn flavones, cassia seed glycosides and phosphatidylcholine is 8:1.5:1.2:0.8.

[0008] Compared with the prior art, in the present application, the Arctium lappa L. water extract contains polyphenols, arctiin and soluble dietary fiber, can adsorb intestinal cholesterol and triglycerides, inhibit lipase activity and reduce exogenous energy absorption; at the same time, it can scavenge oxygen free radicals and protect vascular endothelial cells; the main components of hawthorn flavones are vitexin and quercetin, which can activate the expression of liver LDL receptors, promote cholesterol metabolism and inhibit adipocyte differentiation; cassia seed glycosides can inhibit the activity of liver HMG-CoA reductase (a key enzyme for cholesterol synthesis), reduce endogenous cholesterol production and improve insulin resistance; and the present inventors have unexpectedly found that the Arctium lappa L. water extract, hawthorn flavones and cassia seed glycosides have a synergistic effect: the Arctium lappa L. water extract serves as a core component, on the basis of which, the quercetin in hawthorn flavones can activate the activity of antioxidant enzymes and enhance the antioxidant capacity; cassia seed glycosides can inhibit the expression of inflammatory factors and reduce the damage of inflammatory reactions to vascular endothelium, and the three components synergistically resist oxidation from three aspects of directly scavenging free radicals, activating antioxidant enzymes and inhibiting inflammatory damage, so that the level of vascular endothelial damage markers is significantly reduced. This vascular protection effect not only reduces the damage of hyperlipidemia to blood vessels, but also maintains the normal function of metabolic organs such as the intestine and liver, ensures the persistence of the lipid-lowering effect and avoids the limitation that a single component can only lower blood lipids and cannot improve the pathological microenvironment.

[0009] Further, the present inventors have found that, to realize the synchronous absorption and promotion of the three different polar components, the absorption-promoting component needs to have bidirectional solubility, and the molecular structure of phosphatidylcholine (hydrophilic phosphocholine head and hydrophobic fatty acid tail) exactly meets this requirement: it can spontaneously form nanomicelles, the hydrophobic region inside the micelles wraps the weakly polar cassia seed glycosides and arctiin, the external hydrophilic region combines the polar polyphenols and dietary fiber, and at the same time, the three components are carried through the water-lipid barrier of the intestinal mucosa (the membrane of intestinal epithelial cells is a lipid bilayer structure, and polar components are difficult to directly penetrate), so that phosphatidylcholine can enhance the permeability of the intestinal mucosa, improve the bioavailability of active components, and at the same time, it can promote lipoprotein metabolism and assist in lowering blood lipids.

[0010] In a second aspect, the present application provides the use of the lipid-lowering composition in the preparation of a lipid-lowering drug.

[0011] Further, the hypolipidemic composition plays a role in lowering blood lipid by synergistically lowering serum total cholesterol, triglyceride, low density lipoprotein cholesterol, increasing high density lipoprotein cholesterol, and lowering serum ALT and AST activity.

[0012] In a third aspect, the present application provides a preparation method of the hypolipidemic composition, comprising the following steps:

[0013] (1) separately preparing the water extract of burdock root, the hawthorn flavone and the cassia seed glycoside, and weighing each component according to the ratio of the hypolipidemic composition;

[0014] (2) mixing the water extract of burdock root, the hawthorn flavone, the cassia seed glycoside and the phosphatidylcholine to prepare the composition.

[0015] Further, in step (1), the preparation process of the water extract of burdock root is as follows: grinding dried burdock root into 30-50 mesh, adding purified water and 0.5% cellulase of the total mass of burdock root at a solid-liquid ratio of 1g:10mL-1g:18mL, first enzymolysis at 45-55℃ for 1h, then water extraction at 70-85℃ for 2-3 times, combining the extract, filtering, concentrating, and drying to obtain the water extract of burdock root.

[0016] Further, in step (1), the preparation process of the hawthorn flavone is as follows: taking hawthorn, grinding and refluxing extraction with ethanol of a volume fraction of 60%-70%, purifying the extract with AB-8 type macroporous resin, and drying to obtain the hawthorn flavone.

[0017] Further, in step (1), the preparation process of the cassia seed glycoside is as follows: taking cassia seed, grinding and ultrasonic extraction with ethanol of a volume fraction of 50%-60%, extracting the extract with ethyl acetate, purifying with a silica gel column, and recrystallizing to obtain the cassia seed glycoside.

[0018] In a fourth aspect, the present application provides a hypolipidemic drug containing the water extract of burdock root with high absorption, comprising the composition and pharmaceutically acceptable excipients; the excipients comprise at least one of a filler, a disintegrant, a binder, a lubricant and a solubilizer.

[0019] Further, the dosage form of the drug is an oral preparation; the oral preparation comprises tablets, capsules, granules or oral liquids.

[0020] According to the above technical solution, the present application achieves the following technical effects:

[0021] The biggest limitation of the existing raw material mixing technology is to ignore the bioavailability, and the extract combination of the present application must be matched with phosphatidylcholine to achieve high absorption, which achieves unexpected technical effects.

[0022] Moreover, the application mixes Arctium lappa L. water extract, Cassia seed glycosides and hawthorn flavonoids, and unexpectedly finds that the three have synergistic effects, and when the three are mixed, an unexpected blood lipid-lowering effect is achieved. DETAILED DESCRIPTION

[0023] In order to make the technical means, creative features, purposes and effects of the present application easy to understand, the present application is further described below in combination with specific embodiments.

[0024] Embodiment 1: A high-absorption blood lipid-lowering composition containing Arctium lappa L. water extract, comprising Arctium lappa L. water extract, hawthorn flavonoids, Cassia seed glycosides and phosphatidylcholine in a mass ratio of 6:1:0.8:0.5.

[0025] The preparation process of the above blood lipid-lowering composition is as follows:

[0026] S1 Preparation of Arctium lappa L. water extract

[0027] 1. Take dry Arctium lappa L. with a water content of 2.8%, remove impurities and moldy parts, soak and wash with flowing purified water for 3 times, each time for 5 min, drain and dry in a 60°C air-drying oven until the surface is dry.

[0028] 2. Grind the dried Arctium lappa L. with a universal grinder FW100, pass through a 30-mesh sieve with a mesh size of 0.3 mm, collect the undersize powder and seal and store in a desiccator.

[0029] 3. Weigh the Arctium lappa L. powder, add purified water, stir uniformly, add 5 g of cellulase (material to liquid ratio of 1 g:10 ml, enzyme activity ≥5000 U / g), place in a constant-temperature water bath (model: HH-S4), and incubate at 45°C for 1 h (stirring rate 150 r / min) to obtain an enzyme solution.

[0030] 4. Transfer the enzyme solution to a multifunctional extraction tank (model: TQ-50), heat to 70°C, and extract twice, the first time for 2.5 h with a stirring rate of 100 r / min, and the second time for 2 h; after each extraction, stand for 10 min, discharge the supernatant, and combine all the extraction solutions.

[0031] 5. Filter the extraction solution through a 150-mesh nylon filter cloth to remove coarse fibers and residues, and collect the filtrate; press filter through a 0.22 μm microporous filter membrane (pressure 0.1 MPa) to obtain a clear filtrate.

[0032] 6. Transfer the clear filtrate into a rotary evaporator (model: RE-52AA), set the water bath temperature to 55°C, the vacuum degree to -0.07 MPa, and the rotation speed to 80 r / min; stop concentrating when the relative density reaches 1.15, and obtain a brown extract.

[0033] 7. The extract was transferred to a vacuum drying oven (Model: DZF-6050) at 50°C and a vacuum degree of -0.08 MPa for 8 h. After drying, the extract was ground by a super micro grinder (Model: WFM-1000) and passed through a 100-mesh sieve to obtain a brownish yellow powder of the burdock root extract, which was stored in a sealed container away from light.

[0034] S2 Preparation of Hawthorn Flavonoids

[0035] 1. Dry hawthorn fruits were quickly rinsed with purified water, air-dried at 60°C until the weight was constant, and ground to 20 mesh to obtain hawthorn powder.

[0036] 2. Hawthorn powder was weighed and added to a 60% ethanol aqueous solution (1 g:8 mL) in a round-bottom flask connected to a spherical condenser. The mixture was refluxed at 70°C for 2 h, and then filtered with a 200-mesh filter cloth while hot. The two extracts were combined.

[0037] 3. The extract was transferred to a rotary evaporator and distilled under reduced pressure at 50°C and a vacuum degree of -0.06 MPa until the distillate had no alcohol smell (alcohol content ≤0.5% as detected by alcohol meter), to obtain a hawthorn crude extract.

[0038] 4. AB-8 macroporous resin was soaked in a 95% ethanol aqueous solution for 24 h and column-packed (column height:diameter ratio 5:1) by wet method. The column was washed with 95% ethanol and purified water until no alcohol smell was detected, and then used. The hawthorn crude extract was concentrated to a concentration of 0.15 g / mL and loaded onto the column at a flow rate of 1 BV / h. Then, the column was eluted with purified water at a flow rate of 2 BV / h until the eluate was colorless, and then eluted with a 40% ethanol aqueous solution at a flow rate of 1.5 BV / h. The eluate was collected until no flavonoids were detected.

[0039] 5. The eluate was concentrated under reduced pressure to an extract, which was dried at 50°C under vacuum. The dried extract was ground and passed through an 80-mesh sieve to obtain a light yellow hawthorn flavonoid powder.

[0040] S3 Preparation of Amaranthin

[0041] 1. Dry amaranth seeds were cleaned and ground to 20 mesh for use.

[0042] 2. Amaranth powder was weighed and added to a 50% ethanol aqueous solution (1 g:10 mL) in an ultrasonic extractor (Model: KQ-500DE). The mixture was ultrasonically extracted at a power of 300 W and a temperature of 50°C for 40 min per time with an interval of 5 min, and the extraction was repeated for 3 times. After extraction, the extract was filtered with a 200-mesh filter cloth.

[0043] 3. The extract was concentrated under reduced pressure to remove ethanol. An equal volume of ethyl acetate was added, and the mixture was shaken in a separatory funnel for 10 minutes. The upper ethyl acetate layer was collected and the extraction was repeated.

[0044] 4. 200-mesh silica gel was activated by soaking in chloroform for 2 hours, and then packed in a column (height:diameter ratio 8:1) using the wet method. The ethyl acetate extract was concentrated to a paste, which was dissolved in a small amount of chloroform and then loaded onto the column. The column was eluted with a mixture of chloroform and methanol (volume ratio 8:2) at a flow rate of 1 BV / h. Every 500 mL of eluate was collected and analyzed by thin layer chromatography (TLC) using chloroform-methanol (9:1) as the developing agent. Fractions containing amaranthin were combined.

[0045] 5. The combined fractions were concentrated under reduced pressure to a small volume, and then 5 volumes of methanol were added. The mixture was refrigerated at 5°C for 12 hours to allow the amaranthin to crystallize. The crystals were filtered and washed twice with a small amount of cold methanol. The crystals were recrystallized once more, and then dried under vacuum at 50°C to obtain light yellow amaranthin crystals (purity ≥95%).

[0046] S4. The burdock root water extract, hawthorn flavonoids, amaranthin, and phosphatidylcholine were mixed to obtain the target composition.

[0047] Example 2: A high-absorption-rate blood lipid-lowering composition containing a burdock fruit water extract, comprising burdock root water extract, hawthorn flavonoids, amaranthin, and phosphatidylcholine in a mass ratio of 10:2:1.5:1.

[0048] The preparation process of the above blood lipid-lowering composition is as follows:

[0049] S1. Preparation of burdock root water extract

[0050] 1. Dry burdock root with a water content of 2.8% was obtained. The impurities and moldy parts were removed, and the burdock root was soaked and washed with purified water for 3 times, each time for 5 minutes. After draining, the burdock root was dried in a 60°C air-drying oven until there was no water on the surface.

[0051] 2. The dried burdock root was ground with a universal grinder FW100, and the powder was passed through a 50-mesh sieve with a mesh size of 0.6 mm. The powder was collected and stored in a desiccator.

[0052] 3. The burdock root powder was weighed, and purified water was added. After stirring evenly, 5 g of cellulase was added (material to liquid ratio 1 g:18 ml, enzyme activity ≥5000 U / g). The mixture was placed in a constant-temperature water bath (model: HH-S4) and incubated at 55°C for 1 hour (stirring rate 150 r / min) to obtain an enzyme solution.

[0053] 4. Transfer the enzymatic hydrolysate to a multifunctional extraction tank (model: TQ-50), and heat to 85℃, and extract for 3 times, 2.5h for the first time, stirring rate 100r / min; 2h for the second time; 1.5h for the third time; after each extraction, stand for 10min, and release the supernatant, and combine all the extraction liquid.

[0054] 5. Filter the extraction liquid through 200 mesh nylon filter cloth to remove coarse fibers and residues, and collect the filtrate; and filter through 0.22μm microporous filter membrane under pressure (pressure 0.15MPa) to obtain clear filtrate.

[0055] 6. Transfer the clear filtrate into a rotary evaporator (model: RE-52AA), water bath temperature 65℃, vacuum degree -0.09MPa, rotation speed 80r / min; concentrate to relative density 1.25 to stop concentrating, and obtain brown extract.

[0056] 7. Transfer the extract to a vacuum drying oven (model: DZF-6050), 60℃, vacuum degree -0.09MPa, dry for 12h; after drying, crush with a super micro grinder (model: WFM-1000), pass through 120 mesh sieve, and obtain brownish yellow Arctium lappa L. water extract powder, and store in a sealed and light-proof container.

[0057] S2 Preparation of Hawthorn Flavonoids

[0058] 1. Take dried hawthorn fruit, quickly rinse the surface with purified water, dry at 60℃ until constant weight, crush to 40 mesh to obtain hawthorn powder.

[0059] 2. Take hawthorn powder, add 70% by volume ethanol aqueous solution (solid-liquid ratio 1g:12mL), place in a round-bottom flask, connect a spherical condenser, and extract for 2 times at 80℃ water bath reflux, 2h each time, filter hot with 200 mesh filter cloth, and combine the two extraction liquids.

[0060] 3. Transfer the extraction liquid into a rotary evaporator, and distill under reduced pressure at 60℃, vacuum degree -0.08MPa, and recover ethanol until the distillate has no alcohol smell (detection of distillate alcohol content with alcohol meter ≤0.5%), and obtain hawthorn crude extract.

[0061] 4. AB-8 type macroporous resin is soaked with 95% by volume ethanol for 24h, and wet-packed (column height-diameter ratio 5:1), and sequentially washed with 95% by volume ethanol and purified water until no alcohol smell, and used; hawthorn crude extract is concentrated to a concentration of 0.25g / mL, and loaded at a flow rate of 1BV / h, and then sequentially eluted with purified water at a flow rate of 2BV / h until the effluent is colorless, and with 40% by volume ethanol aqueous solution at a flow rate of 2.5BV / h, and collect the eluate until the effluent has no flavonoid reaction.

[0062] 5. The eluent was concentrated under reduced pressure to a extract residue, and vacuum dried at 50°C. The light yellow hawthorn flavone powder was obtained after being crushed to 80 mesh.

[0063] S3 Preparation of Sphingosine

[0064] 1. The dried Schisandra chinensis was removed from impurities and crushed to 30 mesh for use.

[0065] 2. The Schisandra chinensis powder was weighed and added to 60% ethanol aqueous solution (1g:15mL), and placed in an ultrasonic extraction instrument (model: KQ-500DE) with a power of 400W and a temperature of 60°C. The ultrasonic extraction was performed for 40min each time with an interval of 5min, and the extraction was repeated for 3 times. After extraction, the extract was filtered with 200 mesh filter cloth.

[0066] 3. The extract was recovered by ethanol under reduced pressure until there was no alcohol smell. An equal volume of ethyl acetate was added, and the mixture was shaken in a separatory funnel for 2 times, 10min each time. After the upper layer of ethyl acetate was collected, the two extraction solutions were combined.

[0067] 4. The 300 mesh silica gel was soaked with chloroform for 2h and packed by wet method (column height to diameter ratio 8:1). The ethyl acetate phase was concentrated to extract residue, which was dissolved in a small amount of chloroform and then loaded. The chloroform-methanol mixture (volume ratio 8:2) was used as eluent with a flow rate of 1BV / h, and 1 fraction was collected every 500mL. The thin layer chromatography (TLC) was used for detection (developing agent: chloroform-methanol=9:1), and the fractions containing Sphingosine were combined.

[0068] 5. The combined fractions were concentrated under reduced pressure to a small volume, 5 times the volume of methanol was added, and the mixture was refrigerated at 5°C for 12h. The crystals were precipitated and filtered. The crystals were washed with a small amount of cold methanol twice, and the recrystallization was repeated once. The light yellow Sphingosine crystals were obtained after vacuum drying at 50°C (purity≥95%)

[0069] S4 The burdock root water extract, hawthorn flavone, Sphingosine and phosphatidylcholine were mixed to obtain the target composition.

[0070] Example 3: A high absorption rate of a hypolipidemic composition containing burdock fruit water extract, which includes burdock root water extract, hawthorn flavone, Sphingosine and phosphatidylcholine with a mass ratio of 8:1.5:1.2:0.8.

[0071] The preparation process of the above hypolipidemic composition is as follows:

[0072] S1 Preparation of burdock root water extract

[0073] 1. The dried burdock root with water content of 2.8% was removed from impurities and moldy parts, and soaked with flowing purified water for 3 times, 5min each time. After being drained, the burdock root was dried in a 60°C air drying oven until there was no water on the surface.

[0074] 2. Dry burdock root was crushed by universal pulverizer FW100, and the powder was collected by 30 mesh sieve. The powder was sealed and stored in a desiccator.

[0075] 3. Burdock root powder was weighed and added with purified water. After stirring evenly, 5 g of cellulase (1 g: 15 ml, enzyme activity ≥5000 U / g) was added. The mixture was placed in a constant temperature water bath (model: HH-S4) and incubated at 50°C for 1 h (stirring rate 150 r / min) to obtain an enzyme solution.

[0076] 4. The enzyme solution was transferred to a multifunctional extraction tank (model: TQ-50) and heated to 80°C. The extraction was carried out for 3 times. The first extraction was carried out for 2.5 h at a stirring rate of 100 r / min. The second extraction was carried out for 2 h. The third extraction was carried out for 1.5 h. After each extraction, the mixture was allowed to stand for 10 min, and the supernatant was collected. All the supernatants were combined.

[0077] 5. The extraction solution was filtered through 180 mesh nylon filter cloth to remove coarse fibers and residues, and the filtrate was collected. The filtrate was filtered through a 0.22 μm microporous filter membrane under pressure (pressure 0.12 MPa) to obtain a clear filtrate.

[0078] 6. The clear filtrate was transferred into a rotary evaporator (model: RE-52AA) with a water bath temperature of 60°C, a vacuum degree of -0.08 MPa, and a rotation speed of 80 r / min. The concentration was stopped when the relative density reached 1.15-1.25 to obtain a brown extract.

[0079] 7. The extract was transferred to a vacuum drying oven (model: DZF-6050) and dried at 55°C under a vacuum degree of -0.1 MPa for 10 h. After drying, the extract was crushed by an ultrafine pulverizer (model: WFM-1000) and passed through a 110 mesh sieve to obtain a brownish yellow burdock root water extract powder, which was sealed and stored away from light.

[0080] S2 Preparation of Hawthorn Flavones

[0081] 1. Dry hawthorn fruits were quickly rinsed with purified water, and then air-dried at 60°C until the weight was constant. The dried fruits were crushed to 20-40 mesh to obtain hawthorn powder.

[0082] 2. Hawthorn powder was weighed and added with 65% ethanol aqueous solution (1 g: 10 mL). The mixture was placed in a round-bottom flask and connected with a spherical condenser. The mixture was extracted by refluxing at 75°C for 2 times, each for 2 h. The mixture was filtered hot with 200 mesh filter cloth, and the two extraction solutions were combined.

[0083] 3. The extraction solution was transferred into a rotary evaporator and distilled under reduced pressure at 55°C and a vacuum degree of -0.07 MPa. The ethanol was recovered until there was no alcohol smell in the distillate (alcohol content in the distillate was ≤0.5% detected by alcohol meter). Hawthorn crude extract was obtained.

[0084] 4. AB-8 type macroporous resin is soaked with 95% ethanol for 24 hours, and wet-packed (column height to diameter ratio 5:1). The column is washed with 95% ethanol and purified water in sequence until there is no alcohol smell. The column is ready for use. The hawthorn crude extract is concentrated to a concentration of 0.20 g / mL, and then loaded at a flow rate of 1 BV / h. Then, the column is washed with purified water at a flow rate of 2 BV / h until the effluent is colorless. Then, the column is washed with 40% ethanol aqueous solution at a flow rate of 2.0 BV / h, and the eluate is collected until the effluent has no flavonoid reaction.

[0085] 5. The eluate is concentrated to extract residue under reduced pressure, and then dried at 50°C under vacuum. The dried product is crushed to pass through an 80-mesh sieve to obtain light yellow hawthorn flavonoid powder.

[0086] S3 Preparation of fructus spondii glycoside

[0087] 1. Dry fructus spondii is used, impurities are removed, and the product is crushed to 20 mesh for use.

[0088] 2. The fructus spondii powder is weighed, and 55% ethanol aqueous solution is added (solid to liquid ratio 1 g:12 mL). The mixture is placed in an ultrasonic extraction instrument (model: KQ-500DE) at a power of 350 W and a temperature of 55°C. Ultrasonic extraction is performed for 40 min per time, with an interval of 5 min, and the extraction is performed for a total of 3 times. After extraction, the extract is filtered through a 200-mesh filter cloth.

[0089] 3. The extract is concentrated to remove ethanol under reduced pressure until there is no alcohol smell. An equal volume of ethyl acetate is added, and the mixture is shaken in a separatory funnel for 2 times, 10 min each time. After the mixture is allowed to stand to separate into layers, the upper ethyl acetate phase is collected, and the two extraction solutions are combined.

[0090] 4. 250-mesh silica gel is soaked with chloroform for 2 hours, and wet-packed (column height to diameter ratio 8:1). The ethyl acetate phase is concentrated to extract residue, which is dissolved in a small amount of chloroform and then loaded. A mixture of chloroform and methanol (volume ratio 8:2) is used as an eluent at a flow rate of 1 BV / h. Every 500 mL of eluent is collected, and thin layer chromatography (TLC) is used for detection (developing agent: chloroform-methanol=9:1). The fractions containing fructus spondii glycoside are combined.

[0091] 5. The combined fractions are concentrated to a small volume under reduced pressure, 5 times the volume of methanol is added, and the mixture is stored at 5°C for 12 hours to precipitate crystals. The crystals are filtered, washed with a small amount of cold methanol twice, and recrystallized once. The product is dried at 50°C under vacuum to obtain light yellow fructus spondii glycoside crystals (purity ≥95%).

[0092] S4 The burdock root water extract, hawthorn flavonoids, fructus spondii glycoside, and phosphatidylcholine are mixed to obtain the target composition.

[0093] Comparative Example 1

[0094] In the comparative example 1, compared with example 3, the difference is that the hawthorn flavonoids are replaced by the same amount of burdock root water extract, and the hypolipidemic composition comprises burdock root water extract, cassia glycoside and phosphatidylcholine in a mass ratio of 9.5:1.2:0.8.

[0095] Comparative example 2

[0096] In the comparative example 1, compared with example 3, the difference is that the hawthorn flavonoids are replaced by the same amount of burdock root water extract, and the hypolipidemic composition comprises burdock root water extract, cassia glycoside and phosphatidylcholine in a mass ratio of 9.5:1.2:0.8.

[0097] Comparative example 3

[0098] In the comparative example 3, compared with example 3, the difference is that the cassia glycoside is replaced by the same amount of hawthorn flavonoids, and the hypolipidemic composition comprises burdock root water extract, hawthorn flavonoids and phosphatidylcholine in a mass ratio of 8:2.7:0.8.

[0099] Comparative example 4

[0100] In the comparative example 4, compared with example 3, the difference is that the phosphatidylcholine is replaced by the same amount of poloxamer 188.

[0101] Comparative example 5

[0102] In the comparative example 5, compared with example 3, the difference is that the phosphatidylcholine is removed.

[0103] Performance test

[0104] Experimental animals: 150 SPF level SD male rats, weighing 220-250 g, purchased from Beijing Vito Lihua Experimental Animal Technology Co., Ltd.; feeding environment: temperature 23±2℃, humidity 55±5%, 12h light-dark cycle, free feeding and drinking water;

[0105] High-fat feed: basic feed + 10% lard + 1.2% cholesterol + 0.2% sodium cholate (for modeling);

[0106] Detection reagent: TC, TG, LDL-C, HDL-C detection kit (Nanjing Jiancheng Biological Engineering Institute); ALT, AST detection kit (Roche Diagnostics); burdock glycoside, hawthorn flavonoids, cassia glycoside content detection by high performance liquid chromatography (HPLC) reagent (Merck Chromatography Pure);

[0107] Instrument: automatic biochemical analyzer (Hitachi 7600), high performance liquid chromatograph (Agilent 1260), animal gavage needle, electronic balance (precision 0.1mg).

[0108] Experimental method

[0109] (1) High blood fat model establishment

[0110] In addition to the normal control group (10), the remaining 140 rats were fed with high-fat diet for 4 weeks, and the serum TC≥6.0 mmol / L, TG≥2.2 mmol / L, LDL-C≥3.5 mmol / L were determined as model success, a total of 100 model rats were screened for subsequent experiments.

[0111] (2) Animal grouping and administration scheme

[0112] 100 model rats were randomly divided into 10 groups (10 rats in each group), and another normal control group (10, basal feed + normal saline) was set up, and the grouping was as follows:

[0113] Example 1 group: high-fat diet + Example 1 composition, composition dose 150 mg / kg (calculated as active ingredient);

[0114] Example 2 group: high-fat diet + Example 2 composition, composition dose 150 mg / kg;

[0115] Example 3 group: high-fat diet + Example 3 composition, composition dose 50 mg / kg;

[0116] Comparative example 1-5 group: high-fat diet + corresponding composition, composition dose 150 mg / kg;

[0117] Comparative example 6 group: high-fat diet + atorvastatin calcium suspension, suspension dose 10 mg / kg;

[0118] Model group: high-fat diet + normal saline 150 ml / kg.

[0119] Administration method: once a day, continuous administration for 8 weeks; during the administration period, the model group and each administration group continue to be given high-fat diet, and the normal control group is given basal feed.

[0120] (3) Detection index and method

[0121] ① Blood lipid index: at the end of 8 weeks of administration, the rats were fasted for 12 h (without water), the abdominal aorta was taken blood, centrifuged at 3000 r / min for 15 min to separate serum, and the TC, TG, LDL-C, HDL-C were detected by automatic biochemical analyzer;

[0122] ② Liver injury index: serum ALT and AST activities were detected synchronously;

[0123] ③ Bioavailability: The concentration changes of the three core active ingredients (Arctiin, Fraxinellone, and Sickle Senna Glycoside-Chrysophanol) in rat serum were detected by high-performance liquid chromatography (HPLC) method, and the pharmacokinetic parameters (area under the curve AUC, peak concentration Cmax, and peak time Tmax) were calculated. The relative bioavailability (F%) of each group was calculated with reference group 5 (lacking phosphatidylcholine) as the reference group, and the specific steps were as follows:

[0124] 1. Experimental grouping and sample collection

[0125] Test group: Selecting example groups 1-3, comparative example groups 1-4, and comparative example group 5 as the reference group, and comparative example 6 (Atorvastatin) was detected alone.

[0126] Blood sampling time points: 0.5 mL of blood was taken from the rat retro-orbital plexus at 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h after administration, and placed in a centrifuge tube containing heparin sodium.

[0127] Serum preparation: After blood sampling, centrifuge at 3000 r / min for 15 min, separate the upper serum, and store at -80°C. After all samples were collected, they were uniformly detected.

[0128] 2. Serum sample pretreatment (protein precipitation method)

[0129] Take 100 μL of serum, add 300 μL of chromatographically pure acetonitrile (protein precipitant), vortex for 1 min (at 3000 r / min), and stand for 5 min.

[0130] Centrifuge at 12000 r / min for 10 min, take 200 μL of supernatant, add 800 μL of ultrapure water for dilution (acetonitrile concentration is reduced to 20% to avoid damaging the chromatographic column); after dilution, the solution is filtered through a 0.22 μm organic phase microporous filter, and 5 μL of the filtrate is used for HPLC detection.

[0131] 3. HPLC detection conditions (see Table 1).

[0132] Table 1 HPLC detection conditions .

[0133] 4. Standard curve preparation and parameter calculation

[0134] Standard curve: prepare a series of standard solutions of arctiin (0.1-50 μg / mL), vitexin (0.05-20 μg / mL), chrysophanol (0.02-10 μg / mL) respectively, detect according to the above HPLC conditions, draw the standard curve with "concentration (C) as the abscissa, peak area (A) as the ordinate", and calculate the regression equation (R² are all greater than or equal to 0.999);

[0135] Pharmacokinetic parameters: serum concentration-time data were fitted by DAS 3.0 pharmacokinetic software to calculate AUC0-∞ (0 to 24 h area under the curve of drug-time curve, trapezoidal method), Cmax (peak concentration), Tmax (peak time);

[0136] Relative bioavailability: the AUC0-∞ of the comparative example 5 group was taken as the reference (set as 100%), and the relative bioavailability of each group was calculated according to the formula: F% = (AUC0-∞ of the test group / AUC0-∞ of the comparative example 5 group) x 100%; ; .

[0137] Bioavailability ; .

[0138] The above shows and describes the basic principles and main features of the present application and the advantages of the present application. Those skilled in the art should understand that the present application is not limited by the above examples, and the above examples and descriptions in the specification are only to illustrate the principles of the present application, and various changes and improvements can be made without departing from the spirit and scope of the present application, and these changes and improvements all fall within the scope of the present application. The scope of protection of the present application is defined by the appended claims and their equivalents.

Claims

1. A high absorbability hypolipidemic composition comprising a water extract of Aralia decaisneana Hoo containing a large amount of a water-soluble substance, characterized in that, The lipid-lowering composition comprises burdock root water extract, hawthorn flavonoids, cassia glycosides and phosphatidylcholine in a mass ratio of (6-10):(1-2):(0.8-1.5):(0.5-1).

2. The lipid-lowering composition according to claim 1, characterized in that, The mass ratio of the burdock root water extract, hawthorn flavonoids, cassia glycosides and phosphatidylcholine is 8:1.5:1.2:0.

8.

3. The use of the lipid-lowering composition according to claim 1 or 2 in the preparation of lipid-lowering drugs.

4. The application according to claim 3, characterized in that, The lipid-lowering composition exerts its lipid-lowering effect by synergistically reducing serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and simultaneously reducing serum ALT and AST activity.

5. A method for preparing the lipid-lowering composition according to claim 1 or 2, characterized in that, Includes the following steps: (1) Prepare the burdock root water extract, the hawthorn flavonoids, and the cassia glycosides respectively, and weigh each component according to the proportion of the lipid-lowering composition according to claim 1 or 2; (2) The burdock root water extract, hawthorn flavonoids, cassia glycosides and phosphatidylcholine are mixed to prepare the composition.

6. The preparation method according to claim 5, characterized in that, In step (1), the preparation process of burdock root water extract is as follows: take dried burdock root and crush it to 30-50 mesh, add purified water and 0.5% of the total mass of burdock root cellulase according to the material-liquid ratio of 1g:10mL-1g:18mL, first enzymatically hydrolyze it at 45-55℃ for 1h, and then extract it with water at 70-85℃ 2-3 times. Combine the extracts, filter, concentrate and dry to obtain burdock root water extract.

7. The preparation method according to claim 5, characterized in that, In step (1), the preparation process of hawthorn flavonoids is as follows: hawthorn is taken, crushed and extracted by reflux with 60%-70% ethanol by volume, the extract is purified by AB-8 macroporous resin and dried to obtain hawthorn flavonoids.

8. The preparation method according to claim 5, characterized in that, In step (1), the preparation process of cassia glycoside is as follows: take cassia seeds, crush them and extract them with ultrasonically with 50%-60% ethanol by volume. The extract is then purified by ethyl acetate extraction and silica gel column chromatography. After recrystallization, cassia glycoside is obtained.

9. A lipid-lowering drug containing burdock root water extract with high absorption rate, characterized in that, The composition includes the composition of claim 1 or 2, and further includes pharmaceutically acceptable excipients; said excipients include at least one of fillers, disintegrants, binders, lubricants, and solubilizers.

10. The lipid-lowering drug according to claim 9, characterized in that, The dosage form of the drug is an oral preparation; the oral preparation includes tablets, capsules, granules or oral liquids.