A Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction

Abstract

The present invention discloses a Chinese medicine composition for reducing uric acid obtained by liquid-liquid extraction, and belongs to the technical field of extracting active ingredients of Chinese medicine with solvents. The preparation method of the Chinese medicine composition comprises the following steps: crushing a Chinese medicinal material rich in berberine into a powder, mixing the powder with water in a mass ratio of 1:30-40 to form a suspension, mixing the suspension with a biological wall-breaking enzyme in a mass ratio of 1:0.004-0.006 to obtain an enzymatic solution; mixing the enzymatic solution with an amino-containing hydrophobic low eutectic solvent in a mass ratio of 1:1-3, heating and stirring to obtain a mixed solution, and retaining an organic layer after the mixed solution is allowed to stand for stratification; mixing the organic layer with a back extraction solvent in a mass ratio of 1:1-3 and treating it in a microthermal environment of 30°C-40°C for 6h-10h, standing for stratification to collect the aqueous phase, and drying the aqueous phase to obtain solid berberine powder; mixing the solid berberine powder with a pharmaceutical excipient to obtain the Chinese medicine composition. The present invention improves the extraction efficiency and activity of berberine by constructing a liquid-liquid extraction system.

Description

Technical Field

[0001] The invention belongs to the technical field of extracting active ingredients of traditional Chinese medicines with solvents, and particularly relates to a traditional Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction. Background Art

[0002] Uric acid is the final product of purine metabolism, which is a component of nucleic acids (DNA and RNA) in the human body. It is mainly produced through food intake or the decomposition of cells in the body. Uric acid is metabolized in the body mainly through two pathways: one part is filtered by the kidneys and excreted through urine, and the other part is excreted through the intestines. If uric acid is produced too much or excreted too little, the uric acid level in the blood will increase, leading to hyperuricemia. When the uric acid concentration is too high, urate crystals will be deposited in the joints and other tissues, causing diseases such as gout.

[0003] Traditional Chinese medicine has a long history of treating hyperuricemia and gout. According to TCM theory, gout and hyperuricemia are related to pathological factors such as damp heat, blood stasis, and phlegm in the body. Traditional Chinese medicine can effectively reduce uric acid levels and relieve gout symptoms by clearing away heat and detoxifying, promoting blood circulation and removing blood stasis, and promoting dampness and relieving stranguria. There are many Chinese medicinal materials for treating uric acid in traditional Chinese medicine, including Phellodendron, Pueraria, Coix seeds, and Eucommia. After these medicinal materials are combined, they are decocted in water to obtain a Chinese medicinal decoction for the treatment of hyperuricemia.

[0004] Patent CN106266463A discloses a Chinese medicine composition for treating hyperuricemia and its application. The invention uses Atractylodes lancea, Cinnamon twig, Smilax glabra, Radix Dioscoreae, Herba Plantaginis, Herba Portulacae, Herba Leonuri and Semen Vaccariae as Chinese medicine raw materials, and reasonably adjusts the proportion of each raw material, and then decocts the obtained Chinese medicine composition liquid by adding water, and then prepares a Chinese medicine composition of a specific dosage form. The invention complements each other with each component, and through the compatibility between the components, it enhances the metabolic function of the middle jiao spleen and stomach, accelerates the excretion of metabolic waste of the limbs and six internal organs, and promotes the joints, so that the endogenous metabolic imbalance in the body is quickly restored, on the one hand, it promotes the excretion of uric acid in the blood, relieves the symptoms of hyperuricemia, and on the other hand, it restores and strengthens the metabolic function of the human body, treats both the symptoms and the root causes, thereby regulating the blood uric acid value, restoring it to normal indicators, and making the generation and excretion of uric acid in the blood in the body tend to a dynamic equilibrium state, thereby achieving the purpose of treating hyperuricemia.

[0005] Patent CN116350728A discloses a uric acid lowering and / or anti-inflammatory analgesic Chinese medicine composition and its application, which uses Smilax glabra, Fraxinus chinensis, Coptis chinensis, Phellodendron chinense, Achyranthes bidentata, Fructus Lycopodii, Lily, Astragalus membranaceus and Polygonum cuspidatum as raw materials, and reasonably allocates each raw material ratio, and then obtains the Chinese medicine composition by decocting with water. In this invention, Smilax glabra removes dampness and detoxifies, promotes joint function, and is reused as the monarch medicine; Coptis chinensis, Phellodendron chinense, Fructus Lycopodii, Polygonum cuspidatum and Fructus Lycopodii clear away dampness and heat in the triple energizer, disperse blood stasis and relieve pain, and are ministerial medicines; Achyranthes bidentata, Lily and Astragalus membranaceus invigorate the spleen, benefit the kidney and tonify the lung, and are adjuvant medicines. The above 9 Chinese medicines cooperate with each other, complement each other, and play the effects of purging turbidity and removing dampness, removing blood stasis and relieving pain, and finally obtain a better uric acid lowering effect.

[0006] Patent CN11053859A discloses a Chinese medicine composition for lowering uric acid, and its preparation method and application. The invention uses Chinese yam, Imperata root, Phragmites australis and corn silk as raw materials, and reasonably mixes the raw materials, and then adds water to boil to obtain the Chinese medicine composition. In the invention, Chinese yam nourishes the spleen and stomach, and benefits the lungs and kidneys. The kidneys are responsible for bone and marrow production, and insufficient kidney qi will cause the whole body's muscles and bones to move inflexibly; corn silk and Phragmites australis have the effects of promoting body fluid and quenching thirst, promoting diuresis and reducing swelling; Imperata root clears away heat and promotes body fluid, cools blood and stops bleeding, and has the effect of diuresis, and can relieve heat and numbness, reduce fire and hurt tendons, and the symptoms include joint swelling and pain, severe pain, high fever and thirst, etc. This prescription is used to treat symptoms with the main clinical manifestations of pain, numbness and heaviness in muscles, tendons, bones and joints caused by external evils such as dampness and heat invading the human body, blocking the meridians and causing poor circulation of Qi and blood. It nourishes the spleen and kidneys with its sweet and mild flavors. The kidneys are the foundation of the innate constitution, and the spleen is the foundation of the acquired constitution. If the spleen and kidneys are insufficient, the tendons and veins will not be nourished, dampness and heat will block the meridians, and Qi and blood will not flow smoothly. The method should be to clear away heat and dampness, and to strengthen the spleen and kidneys and promote diuresis.

[0007] The above patents all achieve the therapeutic effect of hyperuricemia by studying a traditional Chinese medicine formula and coordinating the components of the formula. In the traditional Chinese medicine for treating hyperuricemia, there are few active ingredients that directly lower uric acid, so it is necessary to combine it with other traditional Chinese medicines to achieve the overall synergistic effect.

[0008] Berberine is an alkaloid that directly reduces the production of uric acid by inhibiting the activity of xanthine oxidase. However, there are few reports on its extraction in the prior art, mainly because berberine has a high release rate only in hot water. To increase the solubility of berberine in hot water, the temperature needs to be further increased, but too high a temperature will inactivate berberine.

[0009] Therefore, a liquid-liquid double extraction method using a mixed solution at a lower temperature was designed to achieve the extraction of berberine, thereby avoiding the adverse effects of berberine inactivation during high-temperature immersion, and improving the yield and activity of berberine. This is of great significance for improving the efficiency of the application of traditional Chinese medicine in the field of lowering uric acid. Summary of the invention

[0010] According to the deficiencies of the prior art, the present invention improves the extraction efficiency and activity of berberine by constructing a liquid-liquid extraction system to solve the problems in the background technology. Specifically, the technical solution of the present invention includes the following contents:

[0011] A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, the preparation method comprising the following steps:

[0012] The berberine-rich Chinese medicinal material is crushed into a powder, the powder is mixed with water at a mass ratio of 1:30-40 to form a suspension, and the suspension is mixed with a biological wall-breaking enzyme at a mass ratio of 1:0.004-0.006 to obtain an enzymatic solution;

[0013] The enzymatic hydrolyzate and the amino-containing hydrophobic deep eutectic solvent are mixed in a mass ratio of 1:1-3, and then heated and stirred to obtain a mixed solution, and the mixed solution is allowed to stand for stratification and an organic layer is retained;

[0014] The organic layer and the stripping solvent are mixed in a mass ratio of 1:1-3 and treated in a micro-heat environment of 30°C-40°C for 6h-10h, and then the aqueous phase is collected by standing and stratifying, and the aqueous phase is dried to obtain solid berberine powder;

[0015] The solid berberine powder is mixed with pharmaceutical excipients to obtain the traditional Chinese medicine composition.

[0016] Furthermore, the berberine-rich Chinese medicinal materials include Coptis chinensis, Phellodendron chinense, Tripterygium wilfordii or Mahonia suffruticosa.

[0017] Furthermore, the biological wall-breaking enzyme includes cellulase, pectinase or xylanase.

[0018] Furthermore, the conditions for the mixed treatment of the suspension and the biological wall-breaking enzyme include pH 4.0-5.0, temperature 45° C.-55° C. and enzymolysis time 4h-5h.

[0019] Furthermore, the preparation method of the amino-containing hydrophobic deep eutectic solvent comprises the following steps:

[0020] The hydrogen bond acceptor and the hydrogen bond donor are mixed in a molar ratio of 1:1-2, heated to 50°C-70°C and stirred continuously for 10min-20min to obtain the amino-containing hydrophobic deep eutectic solvent.

[0021] Furthermore, the hydrogen bond acceptor includes cyclohexanol, n-octanol or n-decanol.

[0022] Furthermore, the hydrogen bond donor includes p-aminophenol or p-aminobenzyl alcohol. The hydrogen bond donor must contain an amino group. On the one hand, it is used to extract berberine through hydrogen bonding. On the other hand, after mixing with the counter-extraction solvent, it can react with the aldehyde group in the counter-extraction solvent to form a Schiff base structure, so that berberine is separated from the amino-containing hydrophobic low eutectic solvent, and berberine enters the water phase and is separated.

[0023] Furthermore, the heating and stirring conditions include a temperature of 30° C. to 40° C., a stirring speed of 100 r / min to 300 r / min, and a stirring time of 2 h to 3 h.

[0024] Furthermore, the stripping agent is a mixture of an aldehyde-based solvent and water in a mass ratio of 1:1.

[0025] Furthermore, the aldehyde-based solvent includes acetaldehyde, propionaldehyde or valeraldehyde.

[0026] Furthermore, the pharmaceutical excipients include microcrystalline cellulose, magnesium stearate, cross-linked polyvinylpyrrolidone and glycerol.

[0027] A Chinese medicine composition prepared by a method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction.

[0028] Furthermore, the Chinese medicine composition can be prepared into preparation forms such as tablets, capsules, granules, oral liquids or suspensions according to actual application scenarios.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] (1) The present invention utilizes the lone electron pair effect of the oxygen atom in the berberine structure to creatively synthesize an amino-containing hydrophobic low eutectic solvent with a reactive functional group. The amino group on the amino-containing hydrophobic low eutectic solvent forms a hydrogen bond with the oxygen atom to extract berberine into the organic phase where the amino-containing hydrophobic low eutectic solvent is located. Then, the aldehyde-based solvent contained in the stripping agent is used to react with the amino-containing hydrophobic low eutectic solvent to form a covalent bond of a Schiff base structure, thereby competitively binding to the amino-containing hydrophobic low eutectic solvent, so that the amino-containing hydrophobic low eutectic solvent is separated from the berberine. The separated berberine enters the aqueous phase and is dried to remove water to obtain a solid berberine powder. The solid berberine powder is then mixed with conventional pharmaceutical excipients to prepare a traditional Chinese medicine composition having a good uric acid-lowering effect.

[0031] (2) The present invention has found through experimental research that the berberine extraction efficiency is low when the berberine-rich Chinese medicinal materials are directly boiled in water in a conventional manner, and the high temperature of long-term water boiling is likely to inactivate berberine. Therefore, the present invention combines the wall-breaking effect of biological wall-breaking enzymes to release berberine into the aqueous solution to the greatest extent to form an enzymolysis solution. Since the enzymolysis solution also contains biological wall-breaking enzymes, the conventional method for removing the biological wall-breaking enzymes is to adopt high-temperature inactivation, but high-temperature inactivation will cause berberine inactivation. The amino-containing hydrophobic low eutectic solvent designed and synthesized by the present invention can avoid the influence of high-temperature inactivation of biological wall-breaking enzymes on berberine, thereby extracting berberine from the enzymolysis solution, thereby improving the activity of the extracted berberine. DETAILED DESCRIPTION

[0032] The technical solution of the present invention will be clearly and completely described below through the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention.

[0033] Unless otherwise specified, the raw materials and reagents used in the present invention are commercially available or can be prepared by known methods.

[0034] Preparation Example 1:

[0035] The preparation method of the amino-containing hydrophobic deep eutectic solvent specifically comprises the following steps:

[0036] Place 10 mol of cyclohexanol and 10 mol of p-aminobenzyl alcohol in a flask, add a magnetic stirrer, stir at a speed of 100 r / min, then heat to 50°C and stir for 20 minutes. After stirring, stop heating, cool to room temperature and store for later use.

[0037] Preparation Example 2:

[0038] The preparation method of the amino-containing hydrophobic deep eutectic solvent specifically comprises the following steps:

[0039] Place 10 mol of cyclohexanol and 20 mol of p-aminophenol in a flask, add a magnetic stirrer, stir at a speed of 100 r / min, then heat to 50°C and stir for 10 minutes. After stirring, stop heating, cool to room temperature and store for later use.

[0040] Preparation Example 3:

[0041] The preparation method of the amino-containing hydrophobic deep eutectic solvent specifically comprises the following steps:

[0042] Place 10 mol of n-octanol and 10 mol of p-aminobenzyl alcohol in a flask, add a magnetic stirrer, start stirring at a speed of 100 r / min, then heat to 60°C and stir for 15 minutes. After stirring, stop heating, cool to room temperature and store for later use.

[0043] Preparation Example 4:

[0044] The preparation method of the amino-containing hydrophobic deep eutectic solvent specifically comprises the following steps:

[0045] Place 10 mol of n-octanol and 20 mol of p-aminophenol in a flask, add a magnetic stirrer, stir at 100 r / min, then heat to 60°C and stir for 15 min. After stirring, stop heating, cool to room temperature and store for later use.

[0046] Preparation Example 5:

[0047] The preparation method of the amino-containing hydrophobic deep eutectic solvent specifically comprises the following steps:

[0048] Place 10 mol of n-decanol and 10 mol of p-aminobenzyl alcohol in a flask, add a magnetic stirrer, start stirring at a speed of 100 r / min, then heat to 70°C and stir for 20 minutes. After stirring, stop heating, cool to room temperature and store for later use.

[0049] Preparation Example 6:

[0050] The preparation method of the amino-containing hydrophobic deep eutectic solvent specifically comprises the following steps:

[0051] Place 10 mol of n-decanol and 10 mol of p-aminophenol in a flask, add a magnetic stirrer, stir at 100 r / min, then heat to 70°C and stir for 20 minutes. After stirring, stop heating, cool to room temperature and store for later use.

[0052] Embodiment 1: A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, characterized in that the preparation method comprises the following steps:

[0053] 100g of Coptis chinensis was chopped and crushed in an ultrafine grinder, and then sieved with a 100-mesh screen to obtain a powder. Deionized water 30 times its own weight was added to the powder and mixed and stirred to form a suspension, and then cellulase was added according to 0.004 times the weight of the suspension, and then hydrochloric acid was added dropwise to the suspension and stirred continuously until the pH was 4.0 measured by a pH meter, and then the addition of hydrochloric acid was stopped, and the acid-adjusted suspension was heated to 45°C for a timed reaction of 4 hours to obtain an enzymatic solution.

[0054] The amino-containing hydrophobic low eutectic solvent of Preparation Example 1 with the same mass as the enzymatic hydrolyzate was added to the enzymatic hydrolyzate and mixed, then heated to 30°C, set the speed to 100r / min, and stirred for 2h. After stirring, the mixed solution was allowed to stand at room temperature until the solution was completely separated, the aqueous phase was removed, and the organic layer containing the amino-containing hydrophobic low eutectic solvent was mixed with an equal mass of the stripping solvent (composed of an equal mass of acetaldehyde and deionized water) and slightly heated to 30°C for 6h. After the micro-heat treatment, the layers were allowed to stand and the collected aqueous phase was dried and dehydrated to obtain solid berberine powder, which was weighed 5.01g on an electronic balance and had a yield of 5.01% (calculated based on the weight of Coptis chinensis).

[0055] Solid berberine, microcrystalline cellulose, magnesium stearate, cross-linked polyvinylpyrrolidone and glycerol are mixed and granulated in a weight ratio of 1:2:0.02:0.2:0.1 to obtain a traditional Chinese medicine composition.

[0056] Embodiment 2: A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, characterized in that the preparation method comprises the following steps:

[0057] 100g of Coptis chinensis was chopped and crushed in an ultrafine grinder, and then sieved with a 100-mesh screen to obtain a powder. Deionized water 32 times its own weight was added to the powder and mixed and stirred to form a suspension, and then cellulase was added according to 0.004 times the weight of the suspension, and then hydrochloric acid was added dropwise to the suspension and stirred continuously until the pH was 4.0 measured by a pH meter, and then the addition of hydrochloric acid was stopped, and the acid-adjusted suspension was heated to 45°C for a timed reaction of 4 hours to obtain an enzymatic solution.

[0058] The amino-containing hydrophobic low eutectic solvent of Preparation Example 2 with the same mass as the enzymatic hydrolyzate was added to the enzymatic hydrolyzate and mixed, then heated to 32°C, set the speed to 100r / min, and stirred for 2h. After stirring, the mixed solution was allowed to stand at room temperature until the solution was completely separated, the aqueous phase was removed, and the organic layer containing the amino-containing hydrophobic low eutectic solvent was mixed with an equal mass of the stripping solvent (composed of an equal mass of acetaldehyde and deionized water) and slightly heated to 32°C for 7h. After the micro-heat treatment, the layers were allowed to stand and the collected aqueous phase was dried and dehydrated to obtain solid berberine powder, which was weighed 5.14g on an electronic balance and had a yield of 5.14% (calculated based on the weight of Coptis chinensis).

[0059] Solid berberine, microcrystalline cellulose, magnesium stearate, cross-linked polyvinylpyrrolidone and glycerol are mixed and granulated in a weight ratio of 1:3:0.02:0.3:0.2 to obtain a traditional Chinese medicine composition.

[0060] Embodiment 3: A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, characterized in that the preparation method comprises the following steps:

[0061] 100g of Phellodendron amurense was chopped and crushed in an ultrafine grinder, and then sieved with a 100-mesh screen to obtain a powder. Deionized water 34 times its own weight was added to the powder and mixed and stirred to form a suspension, and then pectinase was added according to 0.005 times the weight of the suspension, and then hydrochloric acid was added dropwise to the suspension and stirred continuously until the pH was 4.5 measured by a pH meter, and then the addition of hydrochloric acid was stopped, and the acid-adjusted suspension was heated to 50°C and reacted for 4 hours to obtain an enzymatic solution.

[0062] Add the amino-containing hydrophobic low eutectic solvent of Preparation Example 3 with a mass of 2 times the mass of the enzymatic hydrolysate to the enzymatic hydrolysate and mix, then heat to 34°C, set the speed to 200r / min, and stir for 2h. After stirring, let the mixed solution stand at room temperature until the solution is completely separated, remove the aqueous phase, and mix the organic layer containing the amino-containing hydrophobic low eutectic solvent with the back extraction solvent (composed of an equal mass of propionaldehyde and deionized water) in a mass ratio of 1:2 and slightly heat to 34°C for 8h. After the micro-heat treatment, let it stand and separate, collect the aqueous phase, dry and remove water to obtain solid berberine powder, weigh 5.32g on an electronic balance, and the yield is 5.32% (calculated by the weight of Coptis chinensis).

[0063] Solid berberine, microcrystalline cellulose, magnesium stearate, cross-linked polyvinylpyrrolidone and glycerol are mixed and granulated in a weight ratio of 3:3:0.025:0.3:0.2 to obtain a traditional Chinese medicine composition.

[0064] Embodiment 4: A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, characterized in that the preparation method comprises the following steps:

[0065] 100g of three needles were chopped into pieces and crushed in an ultrafine grinder, and then sieved with a 100-mesh screen to obtain a powder. Deionized water 36 times its own weight was added to the powder and mixed and stirred to form a suspension, and then pectinase was added according to 0.005 times the weight of the suspension, and then hydrochloric acid was added dropwise to the suspension and stirred continuously until the pH was 4.5 measured by a pH meter, and then the addition of hydrochloric acid was stopped, and the acid-adjusted suspension was heated to 50°C and reacted for 5 hours to obtain an enzymatic solution.

[0066] Add the amino-containing hydrophobic low eutectic solvent of Preparation Example 4, which is twice the mass of the enzymatic hydrolyzate, to the enzymatic hydrolyzate and mix, then heat to 36°C, set the speed to 200r / min, and stir for 3 hours. After stirring, let the mixture stand at room temperature until the solution is completely separated, remove the aqueous phase, and mix the organic layer containing the amino-containing hydrophobic low eutectic solvent with the back extraction solvent (composed of an equal mass of propionaldehyde and deionized water) in a mass ratio of 1:2 and slightly heat to 36°C for 9 hours. After the micro-heat treatment, let it stand and separate, collect the aqueous phase, dry and remove water to obtain solid berberine powder, weigh 5.69g on an electronic balance, and the yield is 5.69% (calculated by the weight of Coptis chinensis).

[0067] Solid berberine, microcrystalline cellulose, magnesium stearate, cross-linked polyvinylpyrrolidone and glycerol are mixed and granulated in a weight ratio of 3:4:0.025:0.4:0.3 to obtain a traditional Chinese medicine composition.

[0068] Embodiment 5: A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, characterized in that the preparation method comprises the following steps:

[0069] 100g of three needles were chopped into pieces and crushed in an ultrafine grinder, and then sieved with a 100-mesh screen to obtain a powder. Deionized water 38 times its own weight was added to the powder and mixed and stirred to form a suspension, and then xylanase was added according to 0.006 times the weight of the suspension, and then hydrochloric acid was added dropwise to the suspension and stirred continuously until the pH was 5.0 measured by a pH meter, and then the addition of hydrochloric acid was stopped, and the acid-adjusted suspension was heated to 55°C for a timed reaction of 5 hours to obtain an enzymatic solution.

[0070] The amino-containing hydrophobic low eutectic solvent of Preparation Example 5, which is 3 times the mass of the enzymatic hydrolyzate, is added to the enzymatic hydrolyzate and mixed, then heated to 38°C, the speed is set to 300r / min, and the stirring is timed for 3h. After the stirring is completed, the mixed solution is allowed to stand at room temperature until the solution is completely separated, the aqueous phase is removed, and the organic layer containing the amino-containing hydrophobic low eutectic solvent is mixed with the back extraction solvent (composed of an equal mass of valeraldehyde and deionized water) in a mass ratio of 1:3 and slightly heated to 38°C for 10h. After the micro-heat treatment is completed, the layers are allowed to stand and the collected aqueous phase is dried and dehydrated to obtain solid berberine powder, which is weighed 5.89g on an electronic balance and has a yield of 5.89% (calculated based on the weight of Coptis chinensis).

[0071] Solid berberine, microcrystalline cellulose, magnesium stearate, cross-linked polyvinylpyrrolidone and glycerol are mixed and granulated in a weight ratio of 4:5:0.03:0.5:0.4 to obtain a traditional Chinese medicine composition.

[0072] Embodiment 6: A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, characterized in that the preparation method comprises the following steps:

[0073] 100g of Euonymus japonicus was chopped into pieces and crushed in an ultrafine grinder, and then sieved with a 100-mesh screen to obtain a powder. Deionized water 40 times its own weight was added to the powder and mixed and stirred to form a suspension, and then xylanase was added according to 0.006 times the weight of the suspension, and then hydrochloric acid was added dropwise to the suspension and stirred continuously until the pH was 5.0 measured by a pH meter, and then the addition of hydrochloric acid was stopped, and the acid-adjusted suspension was heated to 55°C and reacted for 5 hours to obtain an enzymatic solution.

[0074] The amino-containing hydrophobic low eutectic solvent of Preparation Example 6 with a mass of 3 times the mass of the hydrolyzate was added to the hydrolyzate and mixed, then heated to 40°C, the speed was set to 300r / min, and the stirring was timed for 3h. After the stirring, the mixed solution was allowed to stand at room temperature until the solution was completely separated, the aqueous phase was removed, and the organic layer containing the amino-containing hydrophobic low eutectic solvent was mixed with the back extraction solvent (composed of an equal mass of valeraldehyde and deionized water) in a mass ratio of 1:3 and slightly heated to 40°C for 10h. After the micro-heat treatment, the layers were allowed to stand and the collected aqueous phase was dried and dehydrated to obtain solid berberine powder, which was weighed 6.01g on an electronic balance and had a yield of 6.01% (calculated by the weight of Coptis chinensis).

[0075] Solid berberine, microcrystalline cellulose, magnesium stearate, cross-linked polyvinylpyrrolidone and glycerol are mixed and granulated in a weight ratio of 5:6:0.03:0.5:0.5 to obtain a traditional Chinese medicine composition.

[0076] Comparative Example 1:

[0077] A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, characterized in that the preparation method comprises the following steps:

[0078] 100g of Mahonia suffruticosa was chopped and crushed in an ultrafine grinder, and sieved with a 100-mesh screen to obtain a powder. Deionized water 40 times its own mass was added to the powder to mix and stir to form a suspension, and then the suspension was heated to boiling and kept for 30 minutes. Then, the filter residue collected after filtration was added with deionized water 40 times the mass of the filter residue, mixed and heated to boiling and kept for 30 minutes. The filter residue collected by filtration was added with deionized water 40 times the mass of the filter residue again, mixed and heated to boiling and kept for 30 minutes. After filtration, the three filtrates were combined and placed in a drying oven to evaporate the water to obtain solid berberine powder, which was weighed by an electronic balance and weighed 3.21g, with a yield of 3.21%.

[0079] Solid berberine, microcrystalline cellulose, magnesium stearate, cross-linked polyvinylpyrrolidone and glycerol are mixed and granulated in a weight ratio of 5:6:0.03:0.5:0.5 to obtain a traditional Chinese medicine composition.

[0080] Comparative Example 2:

[0081] A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, characterized in that the preparation method comprises the following steps:

[0082] The xylanase in Example 6 was removed and not added, the suspension was heated to boiling and maintained for 60 minutes, then naturally cooled to room temperature, and then the amino-containing hydrophobic deep eutectic solvent of Preparation Example 6 with a mass 3 times that of the suspension was mixed with the suspension, and the other conditions were consistent with Example 6, and the weight of the solid berberine powder obtained was 2.97 g, and the yield was 2.97%.

[0083] Comparative Example 3:

[0084] A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, characterized in that the preparation method comprises the following steps:

[0085] The enzymatic hydrolysate obtained in Example 6 was directly heated to 100° C. for inactivation treatment for 15 min, and then dried to remove water to obtain solid berberine with a weight of 5.94 g and a yield of 5.94%.

[0086] Verify the uric acid lowering effect of the Chinese medicine composition obtained in Examples 1 to 6 and Comparative Examples 1 to 3:

[0087] (1) Establishment of animal model:

[0088] Ten healthy male SD rats were divided into a blank group (1 rat), an example group (6 rats) and a comparative example group (3 rats). The blank group was injected with normal saline, and the example group and the comparative example group were injected with 200 mg potassium oxonate solution (concentration of 0.1 g / mL) per kg body weight of mice twice a day, and the model was established for 14 consecutive days. On the 7th day of modeling, blood was taken to measure the SUA value (serum uric acid value), and then the corresponding Chinese medicine composition of the example group and the comparative example group was administered for treatment, and the administration was continued for 8 consecutive days. On the 14th day, the rats were anesthetized 6 hours after administration and blood was taken to measure the SUA value (serum uric acid value). The results are shown in the following table:

[0089]

[0090] The above-described embodiments are compared with the technical solutions and beneficial effects of the present invention, and it should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention to be protected.

Claims

1. A method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction, characterized in that: The preparation method comprises the following steps: The berberine-rich Chinese medicinal material is crushed into a powder, the powder is mixed with water at a mass ratio of 1:30-40 to form a suspension, and the suspension is mixed with a biological wall-breaking enzyme at a mass ratio of 1:0.004-0.006 to obtain an enzymatic solution; The enzymatic hydrolyzate and the amino-containing hydrophobic deep eutectic solvent are mixed in a mass ratio of 1:1-3, and then heated and stirred to obtain a mixed solution, and the mixed solution is allowed to stand for stratification and an organic layer is retained; The organic layer and the stripping solvent are mixed in a mass ratio of 1:1-3 and treated in a micro-heat environment of 30°C-40°C for 6h-10h, and then the aqueous phase is collected by standing and stratifying, and the aqueous phase is dried to obtain solid berberine powder; The solid berberine powder is mixed with pharmaceutical excipients to obtain the traditional Chinese medicine composition.

2. The method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction according to claim 1, characterized in that: The Chinese medicinal materials rich in berberine include Coptis chinensis, Phellodendron amurense, Tripterygium wilfordii or Mahonia sinensis.

3. The method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction according to claim 1, characterized in that: The biological wall-breaking enzyme includes cellulase, pectinase or xylanase.

4. The method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction according to claim 1, characterized in that: The conditions for mixing the suspension with the biological wall-breaking enzyme include pH 4.0-5.0, temperature 45° C.-55° C. and enzymolysis time 4h-5h.

5. The method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction according to claim 1, characterized in that: The preparation method of the amino-containing hydrophobic deep eutectic solvent comprises the following steps: The hydrogen bond acceptor and the hydrogen bond donor are mixed in a molar ratio of 1:1-2, heated to 50°C-70°C and stirred continuously for 10min-20min to obtain the amino-containing hydrophobic deep eutectic solvent.

6. The method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction according to claim 5, characterized in that: The hydrogen bond acceptor includes cyclohexanol, n-octanol or n-decanol, and the hydrogen bond donor includes p-aminophenol or p-aminobenzyl alcohol.

7. The method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction according to claim 1, characterized in that: The heating and stirring conditions include a temperature of 30° C. to 40° C., a stirring speed of 100 r / min to 300 r / min, and a stirring time of 2 h to 3 h.

8. The method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction according to claim 1, characterized in that: The stripping solvent is formed by mixing an aldehyde-based solvent and water in a mass ratio of 1:

1.

9. The method for preparing a Chinese medicine composition for lowering uric acid obtained by liquid-liquid extraction according to claim 8, characterized in that: The aldehyde-based solvent includes acetaldehyde, propionaldehyde or valeraldehyde.

10. A Chinese medicine composition prepared by the method for preparing a Chinese medicine composition for lowering uric acid by liquid-liquid extraction according to any one of claims 1 to 9.

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