A Chinese medicine composition for reducing hyperuricemia and preparation method thereof

Abstract

The invention relates to a Chinese medicine composition containing liquidambar oil and a preparation method thereof. The liquidambar oil has the effect of inhibiting xanthine oxidase and has a good function of reducing uric acid. The liquidambar oil can be prepared into capsules to prevent the liquidambar oil from volatilizing and maintain its activity stably for a long time.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition for reducing hyperuricemia and a preparation method thereof. Background Art

[0002] Gout is a common metabolic disease, which is characterized by increased purine anabolism and / or decreased uric acid excretion, leading to increased uric acid concentration in the blood. Statistics in recent years show that the prevalence of gout in all age groups is 0.84%.

[0003] At present, the clinical anti-gout drugs are mainly Western medicine, mainly inflammatory interference drugs and uric acid-lowering drugs. The former include colchicine, nonsteroidal anti-inflammatory drugs, and adrenocortical hormones, while the latter include uric acid excretion drugs and uric acid production inhibitors. The production of uric acid in the body is related to purine metabolism. In the final stage of purine metabolism, xanthine produces uric acid under the action of xanthine oxidase (XO). Inhibiting the activity of XO can effectively reduce the production of uric acid. For example, allopurinol can inhibit the activity of xanthine oxidase, thereby reducing the production of uric acid. Although these drugs can effectively reduce the production of uric acid, clinical use has found that these drugs have many adverse reactions, such as nausea, vomiting, diarrhea, allergic reactions, liver and kidney damage, etc. There are also reports on the treatment of gout with traditional Chinese medicine, such as Herba Lycopodii, Polygonum cuspidatum, Panax notoginseng, Phellodendron chinense, Stephania tetrandra, and Phellodendron chinense, but they are all clinical prescriptions of old Chinese medicine practitioners, mainly for clearing heat and removing wind, removing dampness and relieving arthralgia, with unclear mechanism of action and poor efficacy. Therefore, doctors have very few options for clinical medication. There are relatively few Chinese patent medicines currently being developed on the market.

[0004] Liquidambar oil is a volatile oil from the liquidambar resin (also known as liquidambar resin, white gum, cloud fragrance, etc.) of the liquidambar tree (Liquidambar formosana Hance, Hamamelidaceae, Liquidambar genus), and its main components include olefin compounds. It can be used to make incense or as a biofuel. Due to its volatility, its use in the medical field is relatively rare. Summary of the invention

[0005] In order to overcome the defects of the prior art, the present invention utilizes modern Chinese medicine extraction and purification technology to extract the effective part for treating gout from the original Chinese medicine to prepare a suitable preparation. Specifically,

[0006] In a first aspect, the present invention provides a use of liquidambar oil in inhibiting the activity of xanthine oxidase.

[0007] In a second aspect, the present invention provides a xanthine oxidase inhibitor, wherein the inhibitor comprises liquidambar oil.

[0008] The third aspect of the present invention provides a method for preparing liquidambar oil, the method comprising: extracting volatile oil from liquidambar resin.

[0009] Preferably, the preparation method comprises:

[0010] 1) dissolving liquidambar resin by ultrasonic treatment;

[0011] 2) filtering the dissolved Liquidambar formosana resin membrane;

[0012] 3) distilling the filtered filtrate under reduced pressure;

[0013] 4) Azeotropic distillation to prepare maple oil.

[0014] More preferably, the step 1) comprises dissolving liquidambar resin in ethanol, dissolving by ultrasonic, the weight ratio of liquidambar resin to ethanol being 1:(1-3); stirring time being 30-40 min, and ultrasonic time being 50-70 min.

[0015] More preferably, the step 2) comprises a membrane filtration rate of 20-40 kg / min.

[0016] More preferably, the step 3) comprises reducing pressure at -0.04Mpa to 0.05Mpa and a temperature of 90°C to 110°C;

[0017] More preferably, the step 4) comprises azeotropic distillation at -0.04Mpa to 0.05Mpa and a temperature of 100°C to 110°C.

[0018] In a fourth aspect, the present invention provides a use of liquidambar oil in preparing a traditional Chinese medicine composition, wherein the traditional Chinese medicine composition is used for inhibiting the activity of xanthine oxidase.

[0019] Preferably, the Chinese medicine composition can be used to treat diseases related to abnormal purine metabolism. More preferably, the purine includes xanthine. Further preferably, the abnormal purine metabolism leads to increased uric acid.

[0020] More preferably, the disease includes diseases related to abnormal uric acid. Further preferably, the disease includes hyperuricemia (HUA) and diseases of other systems caused by hyperuricemia, including, for example, gout, renal damage, thyroid damage, hypertension, coronary heart disease, arteriosclerosis, heart failure, pulmonary hypertension, diabetes, stroke, etc.

[0021] A fifth aspect of the present invention provides a traditional Chinese medicine composition, comprising maple oil.

[0022] Preferably, the weight percentage of the liquidambar oil is 25-80%.

[0023] Preferably, the Chinese medicine composition is in any dosage form, for example, oral preparation, injection, etc.; more preferably, the Chinese medicine composition is in a dosage form suitable for oral administration, including, for example, capsules, pills, granules, mixtures, tablets, powders, granules, oral liquids, decoctions, and the like.

[0024] Further preferably, the Chinese medicine composition is a capsule, more preferably, the capsule is a microcapsule or a soft capsule. More preferably, the Chinese medicine composition comprises the microcapsule containing maple oil further prepared into other dosage forms, such as tablets, granules, powders, granules, etc.

[0025] Preferably, the Chinese medicine composition includes pharmaceutical excipients. More preferably, the excipients include excipients for preparing any of the above dosage forms. The weight percentage of the excipients is 20-75%.

[0026] More preferably, the weight portions of the liquidambar oil and the adjuvants are adjusted according to different dosage forms, the liquidambar oil is any value or any range in the range of 25-80%, for example 28%, 30%, 35%, 40%, 45%, 49%, 50%, 55%, 60%, 65%, 70%, 75%, 78%, 80% and the like; the pharmaceutical adjuvant is any value or any range in the range of 20-75%, for example 22%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% and the like.

[0027] For example, the weight percentage of maple oil in the microcapsules is 25%-60%, which can be any value or any range within the above range, such as 28%, 30%, 35%, 40%, 45%, 49%, 50%, 55%, 60%, etc., and the weight percentage of the auxiliary materials is any value or any range within the range of 40%-75%, such as 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, etc.

[0028] For another example, in a soft capsule, the weight portion of the maple oil is 60%-80%, more preferably 65%-78%, 68%-75%, 70%-80%, 70%-78%, 72%-72% and the like, and the weight portion of the auxiliary material is any value or any range in the range of 20%-40%, for example: 22%-35%, 25%-32%, 28%-35%, 30%-40%, 32%-38% and the like.

[0029] Or the weight proportions of maple oil and pharmaceutical excipients can be adjusted according to other dosage forms.

[0030] Preferably, the traditional Chinese medicine composition comprises microcapsule excipients, and the microcapsule excipients include wall materials, fillers, and water-soluble emulsifiers.

[0031] Further preferably, the wall material is a mixture of gum arabic and gelatin, and more preferably, the mass fraction of gum arabic is 1-2 parts, and the mass fraction of gelatin is 2-3 parts; the added amount of maple oil is 3-6 times the mass of the wall material.

[0032] Further preferably, the filler is any one or more of isomaltooligosaccharide, sucrose, and glucose; more preferably, the amount of maple oil added is 2-5 times the mass of the filler;

[0033] Further preferably, the water-soluble emulsifier is any one or more of polyglycerol fatty acid ester, sucrose fatty acid ester, polysorbate-80, and more preferably, the amount of the water-soluble emulsifier added is 0.4-10% of the mass of the maple oil;

[0034] Preferably, the excipients include other excipients for preparing non-capsule dosage forms, such as one or more of calcium sulfate, maltose, sodium carboxymethyl starch, pregelatinized starch, hydroxypropyl methylcellulose, sodium lauryl sulfate, calcium stearate, magnesium stearate, and the like.

[0035] Preferably, the traditional Chinese medicine composition comprises 40%-85% of maple oil microcapsules and 15%-60% of other auxiliary materials.

[0036] More preferably, the liquidambar oil microcapsules are any value or any range in the range of 40%-85%, for example: 40%-80%, 45%-75%, 50%-70%, 55%-60%, 75%-85% and the like.

[0037] More preferably, the other auxiliary materials are any value or any range within the range of 15%-60%, for example, 15%-25%, 15%-60%, 20-55%, 25%-55%, 30%-50%, 40%-45% and the like.

[0038] Preferably, the Chinese medicine composition includes soft capsule excipients, more preferably, the soft capsule excipients include glue, plasticizer, water, more preferably, the soft capsule excipients also include additives, masking agents, flavoring agents, preservatives, etc.

[0039] Further preferably, the glue comprises gelatin, and the plasticizer comprises one or more of soybean oil, glycerol, and sorbitol. More preferably, the plasticizer comprises soybean oil.

[0040] Preferably, the ratio of gelatin: plasticizer: water is 100: (30-40): (140-160), more preferably, the ratio of gelatin: plasticizer: water can be any ratio or any range within the above range, for example, 100: (32-38): (145-158), 100: (33-37): (148-155), 100: 36: 152.

[0041] Preferably, the weight ratio of maple oil to soft capsule excipients is (2-4):1.

[0042] A sixth aspect of the present invention provides a method for preparing a Chinese medicine composition, wherein the preparation method comprises preparing the Chinese medicine composition from maple oil and pharmaceutical excipients.

[0043] Preferably, the Chinese medicine composition is a capsule, and the Chinese medicine composition capsule is prepared by using maple oil and pharmaceutical excipients. More preferably, the capsule is a soft capsule or a microcapsule, and even more preferably, the preparation method includes further preparing the microcapsule into other dosage forms.

[0044] More preferably, the Chinese medicine composition is a microcapsule, and the preparation method comprises:

[0045] 1) adding microcapsule excipients into water to prepare an aqueous phase;

[0046] 2) adding maple oil to the water phase for emulsification and homogenization;

[0047] 3) Vacuum and stir the homogenized emulsion;

[0048] 4) The emulsion is dried and granulated to obtain microcapsules containing maple oil.

[0049] In a specific embodiment,

[0050] The preparation method of the Chinese medicine composition microcapsule comprises:

[0051] 1) Add the composite wall material, filler and water-soluble emulsifier into pure water, heat and stir to dissolve, then add the oil-soluble antioxidant and disperse evenly to obtain a water phase;

[0052] 2) adding maple oil to the high-speed shearing water phase for emulsification, and then homogenizing by a high-pressure homogenizer;

[0053] 3) The homogenized emulsion is placed in a temporary storage tank, vacuumed and stirred;

[0054] 4) The emulsion is granulated in one step by a spray-starch fluidized bed drying method to obtain maple oil microcapsules.

[0055] Preferably, the composite wall material in step 1) is a mixture of gum arabic and gelatin, more preferably, the mass fraction of gum arabic is 1-2 parts, and the mass fraction of gelatin is 2-3 parts; the amount of maple oil added is 3-6 times the mass of the wall material.

[0056] Preferably, the heating temperature in step 1) is 50-80°C;

[0057] Preferably, in step 3), the vacuum degree is ≥ 0.09 MPa, and the stirring time is 0.5-1 hour.

[0058] Preferably, in step 4), the particle size of the liquidambar oil microcapsules is 40-100 meshes.

[0059] More preferably,

[0060] In the step 1), the filler is any one of isomaltooligosaccharide, sucrose and glucose; the amount of maple oil added is 2-5 times the mass of the filler; the water-soluble emulsifier is any one of polyglycerol fatty acid ester, sucrose fatty acid ester and polysorbate 80, and the amount of addition is 0.4-10% of the mass of maple oil; the mass of pure water is 0.5-1.2 times the mass of maple oil.

[0061] In the step 2), the high-speed shearing speed is ≥10000 r / min, the emulsification time is 0.5-1 hour, the homogenization operation parameters are low pressure 5-10 MPa, high pressure 60-90 MPa, and the homogenization times are ≥2 times.

[0062] The conditions of the spray-starch fluidized bed drying method in step 4) are: the spray air inlet temperature is 0-50°C, and the starch fluidized bed blast temperature is 60-80°C.

[0063] More preferably, the method for preparing the traditional Chinese medicine composition comprises processing the traditional Chinese medicine composition microcapsules obtained above into other dosage forms, such as tablets, granules, powders, instant preparations, and the like.

[0064] Preferably, the excipients of the other dosage forms include one or more of calcium sulfate, maltose, sodium carboxymethyl starch, pregelatinized starch, hydroxypropyl methylcellulose, sodium lauryl sulfate, calcium stearate, magnesium stearate, and the like.

[0065] Preferably, the traditional Chinese medicine composition comprises 40%-85% of maple oil microcapsules and 15%-60% of other auxiliary materials.

[0066] More preferably, the liquidambar oil microcapsules are any value or any range in the range of 40%-85%, for example: 40%-80%, 45%-75%, 50%-70%, 55%-60%, 75%-85% and the like.

[0067] More preferably, the other auxiliary materials are any value or any range within the range of 15%-60%, for example, 15%-25%, 15%-60%, 20-55%, 25%-55%, 30%-50%, 40%-45% and the like.

[0068] Preferably, the Chinese medicine composition is a soft capsule, more preferably, the soft capsule excipients include a sizing agent, a plasticizer, and water. More preferably, the soft capsule excipients also include additives, masking agents, flavoring agents, preservatives, and the like.

[0069] Further preferably, the glue comprises gelatin, and the plasticizer comprises one or more of soybean oil, glycerol, and sorbitol. More preferably, the plasticizer comprises soybean oil.

[0070] Preferably, the ratio of gelatin: plasticizer: water is 100: (30-40): (140-160), more preferably, the ratio of gelatin: plasticizer: water can be any ratio or any range within the above range, for example, 100: (32-38): (148-158), 100: (33-37): (148-155), 100: 36: 152.

[0071] The preparation method of the soft capsule comprises: preparing the soft capsule by a dripping method.

[0072] Preferably, the preparation method comprises:

[0073] 1) Sol: Sol the gel at a ratio of gelatin: plasticizer: water of 100: (30-40): (140-160); preferably, the sol temperature is 80°C ± 5°C, and the sol time is 25 to 65 minutes;

[0074] 2) Heat preservation and defoaming: vacuumize, heat preservation and defoaming, preferably, the vacuum reading is -0.05Mpa to -0.08Mpa, the temperature is 80℃±5℃, and the heat preservation and defoaming is performed for 4-8h;

[0075] 3) Dropping pills: injecting the pill oil containing maple oil and the glue into a dropping pill machine to prepare capsules, preferably, the weight ratio of maple oil to glue is (2-4):1, and the insulation temperature is controlled at 80-85°C;

[0076] 4) Drying: The capsules are dried, preferably at a drying temperature of 18-25° C., a humidity of 20%-40%, and a drying time of 12-30 hours.

[0077] Preferably, the preparation method prepares the above-mentioned traditional Chinese medicine composition.

[0078] A seventh aspect of the present invention provides a use of liquidambar oil, the above inhibitor or a traditional Chinese medicine composition in reducing uric acid.

[0079] In an eighth aspect, the present invention provides a method for reducing uric acid content, the method comprising applying the above-mentioned maple oil, inhibitor or traditional Chinese medicine composition to an individual.

[0080] According to a ninth aspect of the present invention, there is provided liquidambar oil, which comprises volatile oil extracted from liquidambar resin.

[0081] Preferably, the liquidambar oil comprises β-pinene, α-pinene, camphene, d-limonene, β-caryophyllene, and (-)-β-pinene. More preferably, the content of the above single component is 5%-12.5%. Further preferably, the content of the above single component is 7.5%-12.5%.

[0082] More preferably, the liquidambar oil is prepared by the above-mentioned liquidambar oil preparation method.

[0083] Beneficial effects of the present invention:

[0084] (1) The present invention uses Chinese medicinal materials as raw materials, and the components conform to the theories of traditional Chinese medicine and modern medicine, and conform to the provisions of the pharmacopoeia and the regulations on the management of traditional Chinese medicine. The present invention is an oral medicine, a conventional medicine, a conventional dosage, and can be taken for a long time without obvious toxic and side effects.

[0085] (2) The present invention is a traditional Chinese medicine preparation that acts on the purine metabolic system, inhibits xanthine oxidase, reduces uric acid, has strong targeting, and reduces side effects.

[0086] (3) The present invention treats both the root cause and the symptom, treats the main cause of gout, regulates the metabolism of substances in the body, and reduces the production of uric acid to achieve the therapeutic purpose.

[0087] (4) The present invention prepares the main raw materials in the preparation into capsules, such as soft capsules or microencapsulation, which can resist oxidation and decomposition, improve drug stability, solidify liquid drugs, cover up the bad smell of drugs, and improve patient compliance.

[0088] (5) Preferably, in the preparation process of the microcapsules of the present invention, the bubbles in the emulsion are greatly reduced by vacuum stirring, so that the voids in the microcapsules obtained by spray granulation are significantly reduced. In addition, the wall material is compounded to significantly improve its mechanical strength and stability. The mechanical strength of the microcapsules reaches more than 100g, and the content retention rate of the microcapsules after being placed at 25°C and RH75% for 6 months is greater than 95%, which is sufficient to meet the tableting requirements.

[0089] (6) Preferably, in the preparation process of the soft capsule, the ratio of the capsule material to the plasticizer is adjusted and the preparation parameters are optimized, so that the soft capsule is not easy to harden and the storage period is extended. BRIEF DESCRIPTION OF THE DRAWINGS

[0090] Figure 1Shown is the process flow chart of maple oil production. DETAILED DESCRIPTION

[0091] The present invention will be further described below in conjunction with specific embodiments, and the advantages and features of the present invention will become clearer as the description proceeds. However, these embodiments are exemplary only and do not constitute any limitation to the scope of the present invention. It should be understood by those skilled in the art that the details and forms of the technical solution of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, but these modifications and replacements all fall within the scope of protection of the present invention.

[0092] Embodiment 1 Liquidambar oil preparation method

[0093] Reference Figure 1 The preparation of maple oil comprises the following steps:

[0094] 1) dissolving liquidambar resin by ultrasonic treatment;

[0095] 2) filtering the dissolved Liquidambar formosana resin membrane;

[0096] 3) distilling the filtered filtrate under reduced pressure;

[0097] 4) Azeotropic distillation to prepare maple oil.

[0098] Among them, the key process parameters are as follows:

[0099] Table 1: Process conditions for preparing maple oil

[0100]

[0101]

[0102] The maple oil is obtained, and the main components of the maple oil include olefin compounds, mainly including: β-pinene, α-pinene, camphene, d-limonene, β-caryophyllene and (-)-β-pinene. The content of the above components is 5%-12.5%, preferably 7.5%-12.5%.

[0103] Specifically, the main ingredients and contents are shown in Table 2 (components with a content of less than 5% are not shown):

[0104] Table 2: Main components and relative contents of maple oil

[0105] Serial number Retention time RT CAS Match Ingredient name Relative content% 1 10.752 000127-91-3 94 β-pinene 11.8-12.5 2 8.3692 000080-56-8 97 α-Pinene 9.6-10.2 3 9.3498 000079-92-5 95 Camphene 9.0-9.5 4 13.5009 005989-27-5 99 d-Limonene 8.7-9.2 5 29.5532 000087-44-5 99 β-Caryophyllene 8.5-9.2 6 10.6638 018172-67-3 97 (-)-β-pinene 7.5-8.2

[0106] The main components of samples from different batches were measured and remained relatively stable within the above range.

[0107] Example 2 Analysis of the inhibitory effect of liquidambar oil on xanthine oxidase

[0108] Detection principle:

[0109] Positive drugs and test drugs are added to the ELISA plate, and an equal amount of xanthine oxidase (XO) is added, followed by an equal amount of xanthine as a substrate. The absorbance value is measured at a wavelength of 295 nm. The numerical value reflects the amount of uric acid produced. Based on the obtained data, it is determined whether the drug has an inhibitory effect on xanthine oxidase.

[0110] Material:

[0111] Liquidambar formosana oil sample obtained in Example 1, positive drug allopurinol, xanthine oxidase, xanthine, 96-well plate, sterilized PBS

[0112] instrument:

[0113] Multifunctional microplate reader, vortex mixer, pipette

[0114] step:

[0115] 1. Dissolve the sample in pure water and filter it. Set three concentration gradients with final concentrations of 500μg / ml, 250μg / ml, and 125μg / ml respectively. Prepare allopurinol into a 4mg / ml stock solution and then dilute it 100 times to a 40μg / ml working solution. Prepare xanthine into a 30mM stock solution and then dilute it 10 times to a 3mM working solution. Dilute xanthine oxidase (XO) into a 0.1U / ml working solution.

[0116] 2. The experiment was set up as a blank group, allopurinol (positive drug) and different concentrations of the drug to be tested (experimental group 1, experimental group 2, experimental group 3). Each group was set up with an enzyme group and a non-enzyme group, with 4 replicates each. The enzyme group was added with xanthine oxidase (XO), and the non-enzyme group was the control group, with an equal amount of PBS added.

[0117] 3. Add 110 μl PBS to the blank group, and add 60 μl PBS to each group except the blank group.

[0118] 4. Except for the blank group, 50 μl of the corresponding drugs were added to each well of the other groups, and 40 μl of xanthine oxidase was added to each well of the allopurinol group and the experimental group.

[0119] The control group was added with an equal amount of PBS and incubated at 4°C for 10 min to allow sufficient contact between the drug and the enzyme.

[0120] 5. Then add an equal amount of xanthine as substrate to each well, incubate at 25°C for 15 min, and then measure the absorbance at 295 nm to obtain the value T. The inhibition rate is calculated as:

[0121] Inhibition rate = [1-(Texperiment-Tcontrol) / (Tblank-Tblankcontrol)] x 100%.

[0122] The simple experimental steps are shown in Table 3:

[0123] Table 3: Reaction steps

[0124]

[0125] The groups are shown in Table 4:

[0126] Table 4: Experimental groups

[0127]

[0128]

[0129] Results: See Table 5:

[0130] Table 5: Inhibitory effect of liquidambar oil on xanthine oxidase

[0131]

[0132] As shown in Table 5: The inhibition rate of the allopurinol group is in line with the experimental expectations and has a high inhibition rate, indicating that the detection method is accurate and the experimental results are credible; the increase in the concentration of liquidambar oil is positively correlated with the increase in the inhibition rate of xanthine oxidase, indicating that the inhibition effect is dependent on the drug concentration. Compared with the blank group, the inhibition of each experimental group is significant, and there are significant differences between the experimental groups. Overall, the liquidambar oil sample has a significant in vitro inhibition rate on XO, which can be used as a candidate drug for anti-gout for further screening.

[0133] Example 3 Evaluation of the effect of maple oil on uric acid in mice

[0134] 1. Materials, instruments and animal room facilities

[0135] 60 SPF male Kunming mice (18-20 g, license number: SCXK (Beijing) 20160011), test sample: Liquidambar oil sample (prepared in Example 1), allopurinol (sigmaPHR1377), hypoxanthine, sodium carboxymethylcellulose, Tween 80, uric acid detection kit (Nanjing Jiancheng), multifunctional microplate reader, vortex oscillator, pipette, analytical balance, grinder, mouse gavage device, syringe, balance, centrifuge, etc.: SPF animal laboratory.

[0136] 2. Experimental methods

[0137] 1) Preparation of drug solution

[0138] Sodium carboxymethyl cellulose (CMC) solution: weigh 2.5 g CMC dry powder, add 500 ml pure water, stir and dissolve under heating to make a 0.5% CMC solution, and store it in a sealed container at room temperature after sterilization.

[0139] Blank solution: Take 1.5 ml of Tween 80 and add 98.5 ml of 0.5% CMC solution and mix thoroughly to prepare a 0.5% CMC blank solution containing 1.5% Tween 80. Store at 4°C for later use.

[0140] Allopurinol solution: Weigh 16.24 mg of allopurinol, place in a mortar, add 0.48 ml of Tween 80, grind evenly, slowly add 6.0 ml of 0.5% CMC solution, after sufficient grinding, transfer to a 50 ml centrifuge tube, grind and clean the mortar with 0.5% CMC solution (6.0 ml / time), transfer the cleaning liquid to the same 50 ml centrifuge tube, and clean and transfer 3 times in total (6.0 ml×3), finally add 8.0 ml of 0.5% CMC solution to the 50 ml centrifuge tube to make the total liquid volume reach 32.48 ml, mix well, prepare 0.5 mg / ml allopurinol solution, and store at 4°C for later use.

[0141] Sample solution: Weigh 2.6561g of sample, place in a mortar, add 1ml Tween 80 and grind evenly, add 20ml 0.5% CMC solution while grinding, transfer to a 100ml reagent bottle after sufficient grinding, grind and clean the mortar with 20ml 0.5% CMC solution, transfer and merge the cleaning solution to the same 100ml reagent bottle, and then clean and transfer once more (clean and transfer 2 times in total, 20ml×2). Finally, add 5.4ml of 0.5% CMC solution to the 100ml reagent bottle to make the total liquid volume reach 66.4ml (containing 1.5% Tween 80), mix well, and prepare a 40mg / ml maple oil sample solution after emulsification. On this basis, dilute with 0.5% CMC solution to 50mg / ml, 100mg / ml, 150mg / ml and 200mg / ml maple oil sample solutions respectively, and all maple oil sample solutions are stored at 4℃ for standby use.

[0142] Hypoxanthine solution: Weigh 2.14705g of hypoxanthine, put it in a mortar, add 5.78ml of 0.5% CMC solution and grind evenly, then gradually add 30ml of 0.5% CMC solution in batches while grinding to make the total amount of 0.5% CMC solution reach 35.78ml. After grinding thoroughly, transfer to a 50ml reagent bottle and prepare a 60mg / ml solution for use.

[0143] 2) Mouse breeding

[0144] After the purchased mice arrive, they are first placed in the SP℉ animal house quarantine room. After passing the quarantine, they are transferred to the breeding room and raised in alternating light and dark (12h:12h), with a temperature of 23±2℃ and a humidity of 50±10%, and free food.

[0145] 3. Establishment of hyperuricemia mouse model

[0146] 1) Method for establishing a hyperuricemia mouse model

[0147] The model was established by intraperitoneal injection of hypoxanthine. Mice were injected intraperitoneally with 600 mg / kg hypoxanthine to establish the model.

[0148] The mouse serum was collected 20min, 30min, 60min, 90min and 120min after injection, and the uric acid content in the serum was measured. 0min was before injection, which was equivalent to the control group.

[0149] 2) Measurement method

[0150] The uric acid content in mouse serum was determined by uricase peroxidase coupled method (uric acid determination kit).

[0151] Detection principle: In the detection reaction system, first, uric acid (UA) undergoes a redox reaction with water (H2O) and oxygen (O2) under the catalysis of uricase to generate allantoin and hydrogen peroxide (H2O2), and the generated H202 quickly reacts with 4-aminotipyrine (4-AAP) and N-ethyl-N-(2-hydroxy-3-sulfopropyl)-m-toluidine sodium salt (TOOS) under the catalysis of peroxidase to generate red aldehydimine. The aldehydimine has a strong absorption peak at 550nm. After the reaction, the absorbance of the reaction solution at a specific wavelength is measured to calculate the UA content. The relevant reaction equation is as follows:

[0152] UA+2H2O+O2→Allantoin+CO2+H2O2

[0153] H2O2+4-AAP+TOOS→quinoneimine+5H2O

[0154] Operation steps: The operation steps are carried out according to the instructions of the kit. Using a 96-well plate, 5 ml of mouse serum to be tested is added to each well of the test group, 5 ml of pure water is added to each well of the blank control group, and reagents are added to each well of the standard group.

[0155] 5 μl of the standard solution in the box was added, and then 250 μl of Buffer B was added to each well. After incubation at 37°C for 10 min, the absorbance value A at a wavelength of 510 nm was measured. Three replicate wells were set up in each group, and the average value of the absorbance A of the three wells in each group was taken. The uric acid content in the blood of each group of mice was calculated according to the following calculation formula:

[0156] Uric acid content (μmol / L) = (A 测试 -A 空白 ) / (A 标准 -A 空白 )×C 标准

[0157] Wherein, C is the concentration of the standard in the standard solution, 400 μmol / L.

[0158] 3) Statistical analysis

[0159] The experimental data were statistically processed using SPSS 19.0 software, and the data of each group were compared between groups using t-test analysis.

[0160] 4) Results

[0161] The results are shown in Table 6:

[0162] Table 6 Uric acid in serum after hypoxanthine injection (Mean±SD, n=6)

[0163] Time (time after injection, min) Blood uric acid content (μmol / L) 0 31.75±19.71 20 52.48±63.25 30 85.80±48.52 60 260.42±137.50 90 320.29±105.34 120 252.22±102.34

[0164] According to the above results, after intraperitoneal injection of hypoxanthine, the uric acid concentration in the mouse serum increased significantly after 30 minutes, reached a peak at 1-1.5 hours after injection, and then began to decline. It can be seen that hypoxanthine can be used to establish a hyperuricemia disease model, and the hyperuricemia disease model was successfully established in the present invention.

[0165] 4. Animal experiments

[0166] 1) Grouping

[0167] The mice were randomly divided into 7 groups, with 10 mice in each group.

[0168] (1) Normal control group: Each mouse was gavaged with 350 μl of blank solution every day.

[0169] (2) Model group: Each mouse was intraperitoneally injected with 600 mg / kg hypoxanthine to establish the model, and then gavage with 350 μl of blank solution;

[0170] (3) Allopurinol group (positive drug group): After the model was established, allopurinol 5 mg / kg was administered orally once a day for 7 consecutive days.

[0171] (4) Experimental groups: After the model was established, the four experimental groups were gavaged with 50 mg / kg (ZY1), 100 mg / kg (ZY2), 150 mg / kg (ZY3) and 200 mg / kg (ZY4) of maple oil once a day for 7 consecutive days.

[0172] According to the above modeling of uric acid monitoring, the uric acid concentration increases significantly after 30 minutes, reaches a peak in 1-1.5 hours, and then begins to decline. In order to avoid the difference caused by the decrease in uric acid's own metabolic concentration, we:

[0173] First, each group of mice was serially labeled.

[0174] Secondly, according to the order of group and serial number, mice in each group except the normal control group were injected with hypoxanthine intraperitoneally to establish the model, while mice in the normal control group were injected with an equal volume of 0.5% CMC solution intraperitoneally, and the time of intraperitoneal injection of each mouse was recorded.

[0175] Finally, the administration time was strictly controlled. Still in the same group and serial order, each mouse was administered the drug according to the above method and dosage 10 minutes after the intraperitoneal injection of hypoxanthine to establish the model. The mice in the test group were gavaged with the above sample solutions (including the allopurinol group and the experimental group), and the mice in the normal control group and the model group were gavaged with blank solutions, and the administration time was recorded.

[0176] According to the recorded administration time, the eyeballs of each mouse were removed and blood was collected 30 minutes after oral administration. About 500 μl of blood was collected from each mouse, and the blood was allowed to stand at 37°C for 2 hours, centrifuged at 4°C and 3500 r / min for 10 minutes, and serum was collected for uric acid determination.

[0177] Repeat for 7 days and take the average value.

[0178] During the experiment, the bedding was changed twice to ensure sufficient drinking water and feed.

[0179] The determination method is the same as above.

[0180] 2) Experimental results

[0181] The statistical results of the experimental data are shown in Table 7:

[0182] Table 7: Effects of Liquidambar Oil on Uric Acid in Mice

[0183]

[0184]

[0185] Note: Allopurinol is a positive control. **: p<0.01wNormal control group: #: p<0.05, ##: p<0.01wModel group.

[0186] According to the above results, we can know that:

[0187] 1) Compared with the normal control group, the blood uric acid level of the mice in the model group increased significantly, and the statistical difference was extremely significant, indicating that the model was successfully established: Compared with the model group, the blood uric acid level of the mice in the allopurinol positive drug group decreased significantly, and the statistical difference was also extremely significant, indicating that the positive drug selection and the entire experiment were very successful, and the experimental results related to the maple oil samples were credible.

[0188] 2) The uric acid level in the blood of the experimental group mice showed a dose-dependent change, among which the uric acid level in the 50mg / kg dose group was significantly lower than that in the model group, and the uric acid level in the 100mg / kg dose group was significantly lower than that in the model group, reaching a peak, with statistically significant differences compared with the model group, and 150mg / kg and 200mg / kg were also statistically different from the model group. The above results show that the maple oil sample has a significant effect on reducing the elevated uric acid level in the blood of hyperuricemia model mice when administered orally at a dose range of 50-200mg / kg, with statistically significant differences, and the best effect is achieved at a dose of 100mg / kg.

[0189] Example 4 Preparation of a Chinese medicinal composition containing maple oil

[0190] Solution 1

[0191] (1) Add 24 g of gum arabic, 36 g of gelatin, 100 g of sucrose, and 1.0 g of polysorbate 80 to 200 g of purified water, stir at 80° C. for 30 minutes until completely dissolved, and continue stirring to disperse evenly to prepare an aqueous phase.

[0192] (2) Add 200 g of maple oil to the high-speed sheared water phase at a shear rate of 10,000 r / min and an emulsification time of 30 minutes, and then pass through a high-pressure homogenizer twice, with a low pressure of 5 MPa and a high pressure of 60 MPa.

[0193] (3) Add the emulsion into the feed storage tank, evacuate to 0.09 MPa, and stir for 45 minutes.

[0194] (4) The emulsion was granulated in one step by a spray-starch fluidized bed drying method under the following conditions: an inlet air temperature of 45° C. and a starch fluidized bed blast temperature of 65° C. to obtain maple oil soft capsules with a particle size of 40-100 mesh.

[0195] Other dosage forms can also be prepared based on the above microcapsules, for example,

[0196] (5) The above-mentioned maple oil soft capsules were tableted, and 100 g of excipients (calcium sulfate, maltose, sodium carboxymethyl starch, sodium lauryl sulfate, and magnesium stearate) were added and tableted by a ZP19D rotary tablet press under the conditions of a tableting force of 40 kN and a speed of 28 r / min.

[0197] Scenario 2:

[0198] (1) Add 24 g of gum arabic, 36 g of gelatin, 100 g of glucose and 10 g of sucrose fatty acid ester into 200 g of pure water, stir at 65° C. for 30 minutes until completely dissolved, and continue stirring to disperse evenly to prepare an aqueous phase.

[0199] (2) Add 250 g of maple oil to the high-speed sheared water phase at a shear rate of 12000 r / m

[0200] min, emulsification time 40 minutes, then pass through high pressure homogenizer twice, low pressure 5MPa, high pressure 75MPa.

[0201] (3) Add the emulsion into the feed storage tank, evacuate to 0.095 MPa, and stir for 30 minutes.

[0202] (4) The emulsion was granulated in one step by spray-starch fluidized bed drying method under the following conditions: inlet air temperature 40°C, starch

[0203] The fluidized bed blast temperature was 75°C, and maple oil microcapsules with a particle size of 40-100 mesh were obtained.

[0204] Other dosage forms can also be prepared based on the above microcapsules, for example,

[0205] (5) The above-mentioned maple oil microcapsules were used for tableting, and 150 g of auxiliary materials (calcium sulfate, pregelatinized starch, hydroxypropyl methylcellulose, sodium lauryl sulfate, magnesium stearate) were added and tableted by a ZP19D rotary tablet press under the conditions of a tableting force of 40 kN and a speed of 28 r / min.

[0206] Solution 3

[0207] (1) Add 20 g of gum arabic, 40 g of gelatin, 60 g of isomaltooligosaccharide, and 1.2 g of polyglycerol fatty acid ester into 180 g of purified water, stir at 70° C. for 1 hour until completely dissolved, and continue stirring to disperse evenly to prepare an aqueous phase.

[0208] (2) 300 g of maple oil was added to the high-speed sheared water phase at a shear rate of 13,000 r / m and an emulsification time of 45 minutes. The mixture was then passed through a high-pressure homogenizer for three times at a low pressure of 10 MPa and a high pressure of 70 MPa.

[0209] (3) Add the emulsion into the feed storage tank, evacuate to 0.09 MPa, and stir for 1 hour.

[0210] (4) The emulsion was granulated in one step by a spray-starch fluidized bed drying method under the following conditions: an inlet air temperature of 50° C. and a starch fluidized bed blast temperature of 80° C. to obtain maple oil microcapsules with a particle size of 40-100 mesh.

[0211] Other dosage forms can also be prepared based on the above microcapsules, for example,

[0212] (5) The above-mentioned maple oil microcapsules were tableted, and 200 g of auxiliary materials (calcium sulfate, maltose, sodium carboxymethyl starch, pregelatinized starch, hydroxypropyl methylcellulose, sodium lauryl sulfate) were added and tableted by a ZP19D rotary tablet press under the conditions of a tableting force of 40 kN and a speed of 28 r / min.

[0213] In the above schemes, no matter it is scheme 1, 2 or 3, after being processed into microcapsules, the mechanical strength and stability of maple oil are significantly improved, the mechanical strength of the microcapsules reaches more than 100g, and the content retention rate of the microcapsules after being placed at 25°C and RH75% for 6 months is greater than 95%.

[0214] Example 5 Preparation of soft capsules containing maple oil

[0215] 1 Materials

[0216] (1) Sources of prescription medicinal materials

[0217] Liquidambar oil: Preparation of Example 1

[0218] (2) Source and standards of auxiliary materials

[0219] Soybean oil (Nanchang Baiyun Pharmaceutical Co., Ltd.), gelatin (Baotou Dongbao Biotechnology Co., Ltd.), and purified water all comply with the requirements of the 2020 edition of the Chinese Pharmacopoeia.

[0220] 2 Preparation steps:

[0221] (1) Sol

[0222] Check the status of the glue tank. After confirming that it is intact, close the valve at the bottom of the glue tank, open the purified water valve on the tank body, control the flowmeter to add purified water first, and after the purified water is added, close the purified water valve and start the stirring paddle, and record the amount of purified water added. At the same time, open the hot water circulation valve of the glue tank interlayer for heating, and record the start time of heating, the interlayer temperature, and the temperature inside the tank; add the gelatin and soybean oil in the stainless steel turnover barrel in batches from the feeding port, and finally rinse the soybean oil barrel with purified water and put the rinse liquid into the glue tank together, record the amount of gelatin and soybean oil added, close the feeding port, and the temperature in the tank slowly rises. Control the temperature in the tank at 80℃±5℃, sol 25~65min, sol is completed, turn off the stirring, and record the end time of sol, interlayer temperature and tank temperature. Go to the next process.

[0223] (2) Heat preservation and defoaming

[0224] Check the status of the vacuum pump. After confirming that it is in good condition, turn on the vacuum pump switch, slowly open the vacuum pipe valve of the glue tank, start vacuuming, record the defoaming start time, the temperature inside the tank and the vacuum reading, maintain the temperature inside the glue tank at 80℃±5℃, the vacuum reading at -0.05Mpa~-0.08Mpa, keep warm and defoam for 4-8 hours. When the defoaming is finished, close the vacuum pipe valve, heating switch and vacuum pump switch, and record the defoaming end time, the temperature inside the tank and the vacuum reading.

[0225] (3)Drip pills

[0226] Turn on the power of the pill machine, connect the oil storage barrel and glue storage barrel to the pill machine, and inject the pill oil and glue liquid into the oil tank and glue tank of the pill machine respectively. Adjust the temperature of the glue liquid and pill oil to the process requirements. The insulation temperature of the glue box is controlled at 80-85℃. Clamp the oil pipe with a clamp to drain the bubbles in the oil pipe up to the oil tank, install the dripper, and connect the dripper oil pipe.

[0227] (4) Drying

[0228] During the drying process, the capsules should be turned over every 2 hours. When turning over the capsules, hold the left side of the yarn disc with your left hand, pull out about 3 / 4 of the disc, and turn the capsules around the yarn disc to the middle of the yarn disc with your right hand. Then turn the capsules up and down several times, loosen the adhesive pills, and then evenly spread the capsules over the entire yarn disc. The turning action should be coordinated and the force should be even. Do not use too much force to crush the capsules. Dry for 12 hours at a temperature of 18-25℃ and a humidity of 20-40%.

[0229] 3. Optimization of process conditions:

[0230] (1) Study on capsule shell prescription

[0231] Gelatin, soybean oil and water were used as the shell formulation ingredients. Based on production experience, a variety of shell formulations with different ratios were designed, and the moldability of the finished products was investigated under the same experimental conditions. The results showed that the ratio of gelatin: plasticizer: water was 100: (30-40): (140-160) and the shell hardened after the plasticizer and water ratio was reduced outside the above range, and gradually hardened after three months. When the plasticizer and water ratio was increased outside the above range, the shell was deformed after being stored for 3 months. As the plasticizer and water ratio gradually increased, the deformation ratio gradually increased. Among them, gelatin: soybean oil: water = 100: 36: 152 was the best, and the shell neither hardened nor deformed after being stored for 3 months.

[0232] (2) Study on sol time

[0233] In the experiment, appropriate amounts of water and gelatin were swollen at room temperature for 0 min, 25 min, 45 min, and 65 min, respectively. Then the prescribed amount of soybean oil was added and stirred in a constant temperature water bath at 80°C until dissolved. The bubbles were degassed under a vacuum pressure of 0.05-0.08 MPa until the gelatin solution became clear and transparent without bubbles. The solution was poured into a beaker while hot, taken out after the solution cooled, and the viscosity was measured.

[0234] Table 8 Effect of different swelling time on the viscosity of the glue

[0235] Swelling time Viscosity (E) 0 5.12±0.03 25 4.24±0.04 45 4.12±0.05 65 4.06±0.06

[0236] The results show that the longer the swelling time, the lower the viscosity. The viscosity is close when the swelling time is 25min, 45min, and 65min. The viscosity is the highest at 0min, which may be due to the sufficient swelling, which shortens the sol time and reduces the viscosity accordingly. The sol time of 25-65 minutes is suitable. Considering the cost factor, 25min is used for the following parameter optimization.

[0237] (3) Study on sol temperature

[0238] In the experiment, under the conditions of normal temperature and reduced pressure, an appropriate amount of water and gelatin were swollen for 25 minutes, and then the prescribed amount of soybean oil was added and stirred in a constant temperature water bath at 70°C, 80°C, and 90°C until dissolved. Then, the bubbles were degassed under a vacuum pressure of -0.05 to -0.08 MPa until the gelatin solution was clear and transparent without bubbles. The solution was poured into a beaker while hot, taken out after the solution cooled, and the viscosity was measured.

[0239] Table 9 Effect of different sol temperatures on the viscosity of the sol

[0240] Swelling temperature Viscosity (E) 70 4.25±0.04 80 3.62±0.02 90 5.31±0.02

[0241] From the results in Table 9, it can be seen that the viscosity corresponding to 70-90℃ is within the allowable range, and the preferred temperature is 80℃±5℃. In particular, the viscosity of the system is the lowest at 80℃, so 80℃ is selected as the optimal reaction temperature. This may be because gelatin is more sensitive to temperature, and the higher the temperature, the greater the viscosity; but too low a temperature prolongs the sol time, and the gelatin solution is heated for a long time, which easily increases the viscosity.

[0242] (4) Study on the insulation temperature and insulation time of the glue solution

[0243] The effects of different insulation temperatures and insulation times on the quality of gelatin solution were investigated. Three insulation temperatures were set at 60℃, 70℃, and 80℃, and four insulation times were set at 4, 8, 12, and 24 hours under each temperature condition, with viscosity as the index.

[0244] Table 10 Effect of different holding temperatures and holding times on the viscosity of the adhesive

[0245]

[0246] The results in Table 10 show that when the holding temperature is the same, the longer the holding time, the greater the viscosity; the lower the holding temperature, the greater the viscosity, and the holding time has a greater impact on the viscosity. The viscosity of the product kept at 60-80℃ for 4-24h is within the allowable range, and 80℃±5℃, 4-8h is preferred, and 80℃ for 4h is the best.

[0247] (5) Study on drying temperature and time

[0248] The drying temperature and time of soft capsules are also very important. Gelatin is a high molecular polymer, and too high a temperature will cause changes in the gelatin structure. Therefore, choosing appropriate drying conditions is very important to ensure the quality of soft capsule products. In the experiment, different drying temperatures, humidity and drying times were set, and the disintegration time was used as an indicator to design the effects of different drying temperatures and drying times on capsule materials.

[0249] Table 11 Effects of different drying temperature, humidity and drying time

[0250]

[0251] Table 11 shows that the temperature and humidity are suitable, and the disintegration time is suitable. Too high or too low temperature will affect the disintegration time of soft capsules. According to the enterprise standard, the disintegration time within 30 minutes meets the requirements. However, 15 minutes of disintegration is a relatively stable disintegration time. Therefore, the temperature can be 18-25℃, the humidity can be 20%-40%, and the drying time can be 12-30h. Considering the cost, the drying time should not be too long, especially 12 hours of drying at 25℃ / 40% is the best.

[0252] In summary: The above results adjusted and determined the best preparation process of maple oil soft capsules: 0.375g of maple oil was added to each soft capsule as the capsule core solution, 0.125g of gelatin: soybean oil: water (100:36:152) was added to the capsule shell, the sol time was 25min, the sol temperature was 80℃, and the insulation time and temperature were 80℃ for 4h. The best drying time was 12 hours at a drying temperature and humidity of 25℃ / 40%.

[0253] 4. Soft capsule stability assessment

[0254] The stability of three batches of maple oil soft capsules was investigated, and the accelerated test stability data are shown in Table 12:

[0255] Batch number: (20210501, 20210502, 20210503) Batch: 10,000 capsules / batch Specification: Maple oil: 375 mg

[0256] Packaging: Oral solid pharmaceutical high-density polyethylene bottle

[0257] Inspection conditions: (temperature 40℃±2℃, relative humidity 75%±5%)

[0258] Table 12: Results of accelerated test of maple oil soft capsules

[0259]

[0260] After six months of accelerated stability testing, the appearance, disintegration time, relative density, refractive index and acid value of three batches of maple oil soft capsules showed no significant changes, and the microbial limit test was qualified. The results showed that the maple oil soft capsules had good stability.

[0261] Animal experiments on the maple oil of the present invention show that the maple oil has a good uric acid-lowering effect, but the maple oil is a volatile oil, which is volatile and has a special smell, and has disadvantages such as difficulty in controlling the dosage and inconvenience in carrying. Capsules have the characteristics of preventing oxidative decomposition, improving preparation stability, accurate dosage, and easier to carry and take, so the present invention uses soft capsules or microcapsules to make other dosage forms as the preferred dosage form of the maple oil, and provides patients with a more scientific, reasonable and convenient new dosage form on the basis of maintaining the efficacy of the maple oil, a good medicine for gout.

[0262] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0263] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

[0264] In addition, various embodiments of the present invention may be arbitrarily combined, and as long as they do not violate the concept of the present invention, they should also be regarded as the contents disclosed by the present invention.

Claims

1. A Chinese medicine composition, characterized in that: The Chinese medicine composition is composed of 25-80% by weight of maple oil and 20-75% by weight of pharmaceutical excipients, and the Chinese medicine composition is 1) a soft capsule or 2) a microcapsule, wherein: 1) In the soft capsule, the weight percentage of maple oil is 60%-80%, and the weight percentage of pharmaceutical excipients is 20%-40%. The pharmaceutical excipients include soft capsule excipients, and the soft capsule excipients include gelatin, soybean oil and water, wherein the ratio of gelatin: soybean oil: water is 100: (30-40): (140-160); or, 2) In the microcapsules, the weight percentage of maple oil is 25%-60%, and the weight percentage of pharmaceutical excipients is 40%-75%. The pharmaceutical excipients include microcapsule excipients, and the microcapsule excipients include wall materials, fillers, and water-soluble emulsifiers. The wall material is a mixture of gum arabic and gelatin, wherein the mass fraction of the gum arabic is 1-2 parts and the mass fraction of the gelatin is 2-3 parts; the amount of maple oil added is 3-6 times the mass of the wall material, The filler is any one or more of isomaltooligosaccharide, sucrose, and glucose, and the amount of maple oil added is 2-5 times the mass of the filler. The water-soluble emulsifier is any one or more of polyglycerol fatty acid ester, sucrose fatty acid ester, and polysorbate 80, and the amount of the water-soluble emulsifier added is 0.4-10% of the mass of maple oil. The preparation steps of the maple oil include: 1) Dissolving liquid gum resin by ultrasonic wave: dissolving liquid gum resin in ethanol, dissolving by ultrasonic wave, liquid gum resin: ethanol weight ratio is 1: (1-3); stirring time is 30-40min, ultrasonic time is 50-70min; 2) filtering the dissolved Liquidambar formosana resin through a membrane, wherein the membrane filtration rate is 20-40 kg / min; 3) Vacuum distillation of the filtered filtrate: including vacuum distillation at -0.04Mpa to 0.05Mpa and a temperature of 90°C to 110°C; Azeotropic distillation to prepare maple oil: including azeotropic distillation at -0.04Mpa to 0.05Mpa and temperature: 100°C to 110°C.

2. The Chinese medicine composition according to claim 1, characterized in that: The maple oil comprises 11.8%-12.5% ​​beta-pinene, 9.6%-10.2% alpha-pinene, 9.0%-9.5% camphene, 8.7%-9.2% d-limonene, 8.5%-9.2% beta-caryophyllene and 7.5%-8.2% (-)-beta-pinene.

3. The Chinese medicine composition according to any one of claims 1-2, characterized in that: The Chinese medicine composition is a soft capsule, each of which comprises 0.375 g of maple oil as a capsule core liquid and 0.125 g of a capsule shell, wherein the capsule shell is made of gelatin: soybean oil: water in a ratio of 100:36:

152.

4. The method for preparing the Chinese medicine composition according to any one of claims 1 to 3, characterized in that: The preparation method comprises the steps of preparing a traditional Chinese medicine composition from maple oil and pharmaceutical adjuvants.

5. The preparation method according to claim 4, characterized in that: The Chinese medicine composition is a microcapsule, and the preparation method comprises: 1) Add the microcapsule excipients into water to prepare the aqueous phase; 2) Add maple oil to the water phase for emulsification and homogenization; 3) Vacuum and stir the homogenized emulsion; 4) The emulsion is dried and granulated to obtain microcapsules containing maple oil.

6. The preparation method according to claim 4, characterized in that: The capsule is a soft capsule, and the preparation method of the soft capsule comprises: 1) Sol: Sol the gel at a ratio of gelatin: soybean oil: water of 100: (30-40): (140-160); the sol temperature is 70°C-90°C, and the sol time is 25-65 minutes; 2) Heat preservation and defoaming: vacuumize, heat preservation and defoaming, the vacuum reading is -0.05Mpa ~ -0.08Mpa, the temperature is 60℃-80℃, and the heat preservation and defoaming is 4-8h; 3) Dropping pills: inject the pill oil containing maple oil and the gelatin solution into the dropping pill machine to prepare capsules, and control the insulation temperature at 80-85℃; 4) Drying: Dry the capsules at a temperature of 18-25°C, a humidity of 20%-40%, and dry for 12-30 hours.

7. The preparation method according to claim 6, characterized in that: The preparation method of the soft capsule comprises: 1) Sol: Sol the gel at a ratio of gelatin: soybean oil: water of 100:36:152; the sol temperature is 80° C. and the sol time is 25 minutes; 2) Heat preservation and defoaming: vacuumize, heat preservation and defoaming, the vacuum reading is -0.05Mpa ~ -0.08Mpa, the temperature is 80℃, and the heat preservation and defoaming is 4h; 3) Dropping pills: inject the pill oil containing maple oil and the gelatin solution into the dropping pill machine to prepare capsules, and control the insulation temperature at 80-85℃; 4) Drying: Dry the capsules at a temperature of 25°C and a humidity of 40% for 12 hours.

8. A Chinese medicine preparation, characterized in that: The traditional Chinese medicine preparation is composed of the microcapsules described in any one of claims 1-2 and other auxiliary materials for preparing non-capsule dosage forms, and the traditional Chinese medicine preparation includes further processing the microcapsules into other dosage forms.

9. The Chinese medicine preparation according to claim 8, characterized in that: The Chinese medicine preparation comprises 40%-85% microcapsules and 15%-60% other auxiliary materials.

10. The method for preparing the Chinese medicine preparation according to any one of claims 8 to 9, characterized in that: The preparation method includes processing the microcapsules into other dosage forms.

11. The method for preparing the Chinese medicine preparation according to claim 10, characterized in that: The preparation method of the microcapsules is the preparation method described in any one of claims 4-5.

12. Use of the Chinese medicine composition according to any one of claims 1 to 3 or the Chinese medicine preparation according to any one of claims 8 to 9 in preparing a drug for treating uric acid-related diseases, characterized in that: The uric acid related disease is hyperuricemia.

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