WO2019052310A1 - 一种白凤菜总黄酮提取物及其制备方法与治疗高尿酸血症的用途 - Google Patents

一种白凤菜总黄酮提取物及其制备方法与治疗高尿酸血症的用途 Download PDF

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WO2019052310A1
WO2019052310A1 PCT/CN2018/101168 CN2018101168W WO2019052310A1 WO 2019052310 A1 WO2019052310 A1 WO 2019052310A1 CN 2018101168 W CN2018101168 W CN 2018101168W WO 2019052310 A1 WO2019052310 A1 WO 2019052310A1
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extract
baifengcao
total flavonoid
flavonoid extract
preparing
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French (fr)
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袁慧君
殷婷婷
洪绯
于娟
曾金香
王世聪
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漳州片仔癀药业股份有限公司
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Priority to KR1020207011228A priority Critical patent/KR20200055765A/ko
Priority to JP2020537273A priority patent/JP7166345B2/ja
Publication of WO2019052310A1 publication Critical patent/WO2019052310A1/zh
Priority to US16/821,314 priority patent/US11298390B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
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    • B01D15/08—Selective adsorption, e.g. chromatography
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10—Preparation or pretreatment of starting material
    • A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material

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  • the invention belongs to the field of medicines or health care products, and particularly relates to an extract of total flavonoids of Baifengcao, a preparation method thereof and the use thereof for treating hyperuricemia.
  • Gout is a metabolic disease caused by the deposition of monosodium urate crystals in joints, cartilage and kidneys due to an increase in blood uric acid levels due to a decrease in sputum metabolism and/or uric acid excretion. It is mainly characterized by recurrent joint redness, swelling, heat, pain and dysfunction, and even joint deformity, nephrolithiasis and uric acid nephropathy. Hyperuricemia caused by decreased or increased uric acid excretion is the main cause of gout. Hyperuricemia is not only a direct cause of gout, but also closely related to metabolic syndrome, type 2 diabetes, hypertension, cardiovascular disease, and chronic kidney disease. The pathogenesis of hyperuricemia and gout is related to genetic factors, environmental factors, glycogen accumulation disease, renal insufficiency, blood diseases and drugs.
  • xanthine oxidase inhibitor urate anion transporter 1 (URAT1) inhibitor
  • urate oxidase Clinically used drugs for regulating uric acid metabolism include allopurinol and probenecid.
  • the drugs used to treat acute gouty arthritis include colchicine, non-steroidal anti-inflammatory drugs and glucocorticoids.
  • these drugs have many side effects, such as headaches, rashes, edema, gastrointestinal bleeding, chronic renal papillary necrosis and fatal hypersensitivity syndrome, etc., which has led to a great limitation in their clinical application.
  • Gynura formosana Kitam is a perennial herb of the genus Trichosanthes, also known as the white-backed sunflower, and the white sedge, which is rich in vitamins, alkaloids and flavonoids. Used plants. Studies have shown that Baifengcai is mainly used for the treatment of diseases such as pneumonia, lung cancer, hepatitis, liver cirrhosis and hypertension, and it also has the effect of detoxification and detoxification.
  • Baifengcao extract can be used for treating hyperuricemia.
  • the present invention provides a total flavonoid extract of Baifengcai, and further provides a preparation method and use thereof.
  • the invention provides a total flavonoid extract of white phoenix, which contains 80-85% rutin by weight percentage.
  • the invention also provides a preparation method of the above-mentioned total flavonoid extract of Baifengcai, comprising the following steps:
  • the method for preparing a total flavonoid extract of Baifengcao wherein the enzymatic hydrolysis step is carried out by using a complex enzyme consisting of papain, cellulase and pectinase.
  • the ratio of the weight of the complex enzyme to the white phoenix is 1:5 to 1:3.
  • the method for preparing a total flavonoid extract of Baifengcai wherein the weight ratio of papain, cellulase and pectinase is (0.5-1.5): (2-5): 1-3);
  • the weight ratio of papain, cellulase and pectinase in the composite enzyme is 1:3:2.
  • the macroporous resin A is selected from at least one of AB-8, DM-130, HZ841, ZH-00, ZH-01, ZH-02, ZH-03, CAD-40, CAD-45, and BS-30. ;
  • the macroporous resin B is at least one selected from the group consisting of D-101, D-140, D-141, XAD-3, XAD-4, HP-20, HP-21, LD-605, and LSA-10.
  • the method for preparing a total flavonoid extract of Baifengcao wherein the extraction solvent is water, and the ratio of the weight of the white phoenix to the water is 1: (20-60).
  • the eluting solvent is an aqueous ethanol solution having a volume concentration of 70-80%, and the elution speed is 3-15 m/h.
  • the eluting solvent is an aqueous ethanol solution having a volume concentration of 75%, and the elution speed is 5 m/h.
  • the concentration of total flavonoids of Baifengcao in the concentrated solution is 0.5 mg/mL.
  • the filtrate is added to an extraction tank containing macroporous resin A, and stirred at 30 ° C, 80-150 rpm 6- 24 hours, filtration, taking the macroporous resin A after adsorption, adding 10-30 times the volume of 70-95% ethanol solution to the weight of the macroporous resin A, and then at 30 ° C, 80-150 rpm Stir for 6-24 hours and filter to obtain an extract.
  • the pH of the extract is adjusted to 4-8 by using hydrochloric acid or sodium hydroxide.
  • the drying is freeze-drying.
  • the invention also provides the extract of total flavonoids of Baifengcao prepared by the above preparation method.
  • the invention also provides a pharmaceutical preparation, wherein the total flavonoid extract of Baifengcao, or the extract of total flavonoids of Baifengcao prepared by the above preparation method, is used as an active ingredient, and is prepared according to a conventional process by adding conventional auxiliary materials. Tablets, capsules, powders, mixtures, pills, granules, syrups, patches, suppositories, aerosols, ointments or injections.
  • the conventional excipients are: fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, matrices, and the like.
  • Filling agents include: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.
  • disintegrating agents include: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, Cross-linked polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, croscarmellose sodium, etc.
  • lubricants include: magnesium stearate, sodium lauryl sulfate, talc, silica, etc.
  • suspending agent Including: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, etc.
  • binders include: starch syrup, polyvinylpyrrolidone
  • the invention also provides the extract of total flavonoids of Baifengcao, the total flavonoid extract of Baifengcao prepared by the above preparation method, or the application of the above pharmaceutical preparation in preparing medicines or health care products for treating hyperuricemia.
  • the invention also provides the extract of total flavonoids of Baifengcao, the total flavonoid extract of Baifengcao prepared by the above preparation method, or the application of the above pharmaceutical preparation in preparing medicines or health care products for treating gout.
  • the present invention extracts and isolates a total flavonoid extract of Baifengcao containing 80-85% rutin, and the results of the pharmacodynamic experiment show that the extract can reduce the liver of the hyperuricemia model mouse to some extent.
  • the activity of endogenous xanthine oxidase, reducing the synthesis of uric acid, has a certain effect of reducing uric acid, and can be used as a potential drug for treating hyperuricemia or treating gout;
  • Figure 1 is a map of an eluent in Experimental Example 1 of the present invention.
  • Figure 3 is an HPLC chromatogram of a solution of rutin reference solution in Example 1 of the present invention.
  • Example 4 is an HPLC chromatogram of the extract of total flavonoids of Baifengcao prepared in Example 1 of the present invention.
  • Baifengcai was collected from Dengke Village, Longwen District, Zhangzhou City, Fujian province, and was identified as Baifengcai.
  • the total flavonoid extract of Baifengcao in this example was prepared according to the following method:
  • the total flavonoid extract of Baifengcai was identified by infrared spectroscopy according to the following method:
  • Liquid chromatography conditions guard column: Eclipse XDB-C18 AnalyticalGuard Column (4.6 ⁇ 12.5 mm, 5 ⁇ m): ZOR BZX Eclipse XDB-C18 (4.6 ⁇ 150 mm, 5 ⁇ m); flow rate: 0.5 mL / min; column temperature: 35 ° C; Detection wavelength: 368 nm, 254 nm, 210 nm; injection volume: 10 ⁇ L; mobile phase: 0.03% formic acid aqueous solution (A), acetonitrile (B); gradient elution procedure is as follows: 0 to 10 min, 20% B; 10 to 12 min, 20 % ⁇ 24%B; 12 ⁇ 20min, 24%B; 20 ⁇ 25min, 24% ⁇ 30%B; 25 ⁇ 48min, 30%B.
  • 0.001 g of rutin was accurately weighed and dissolved in 1 mL of methanol to prepare a single reference solution of 1 mg/mL. It was filtered through a disposable filter and placed in a small test tube for use.
  • the reference solution and the test solution (the white flavonoid extract prepared in Example 1 were prepared to prepare a methanol solution having a concentration of 1 ⁇ g/ ⁇ L), and the detection and analysis were carried out according to the conditions of liquid chromatography.
  • the rutin reference solution can be completely separated within 10 minutes.
  • the chromatographic baseline is basically straight, and the chromatographic peak has no tailing phenomenon, and the impurities are not disturbed, and the peak is peaked. Earlier, its retention time was 2.745 min.
  • the total flavonoid extract of Baifengcao in this example was prepared according to the following method:
  • the rutin in the total flavonoid extract of Baifengcao of this example was determined according to "under B" in Example 1. According to the measurement and analysis, in the HPLC spectrum, the rutin content in the total flavonoid extract of Baifengcao in the present example was 80%.
  • the total flavonoid extract of Baifengcao in this example was prepared according to the following method:
  • the rutin in the total flavonoid extract of Baifengcao of this example was determined according to "under B" in Example 1. According to the measurement and analysis, in the HPLC spectrum, the rutin content in the total flavonoid extract of Baifengcai in the present example was 85%.
  • Intraperitoneal injection of jaundice-induced hyperuricemia model increased the body's uric acid precursor content, resulting in increased uric acid production, resulting in a model of hyperuricemia in mice.
  • To explore the total flavonoids of Baifengcao by administering the total flavonoid extract of Baifengcao to hyperuricemia mice by the inhibition rate of uric acid in the serum, the inhibition rate of anhydride and the inhibition rate of hepatic xanthine oxidase activity. The effect of the extract on gout symptoms caused by hyperuricemia.
  • the total flavonoid extract of Baifengcao was prepared as a test drug according to the method of Example 1.
  • mice Male Kunming mice, 84 rats, weighing 28 ⁇ 2g, were randomly divided into 7 groups, which were blank group, model control group, gout tablet group, allopurin group, and total flavonoids extract of Baifengcao. Low dose group.
  • the positive group was given Gout and Tablets (9.6mg/10g) and allopurinol (0.2mL/10g).
  • the high, middle and low doses of Baifengcaan were administered with 24mg/10mL, 12mg/10mL and 6mg/10mL respectively.
  • An aqueous solution of total flavonoid extract of the vegetable, the model control was administered with an equal volume of physiological saline for 11 consecutive days, once per day,
  • mice were intraperitoneally injected with 10% xanthine prepared by using 0.8% CMC-Na as a solvent. After 0.5 h of modeling, the mice were subjected to eyeball extraction and blood was taken. Immediately after the blood was taken, the mouse liver was dissected and the liver was removed and stored at a low temperature. The obtained blood sample was centrifuged at 3000 r/min for 5 min, and serum was taken. Uric acid and creatinine were measured according to the kit instructions.
  • mice Immediately after blood collection, the mice were sacrificed, the liver was quickly removed, weighed, and 10% homogenate was prepared by adding physiological saline pre-cooled to 4 ° C, centrifuged at 3000 r/min for 10 min, and the supernatant was taken and determined according to the method specified in the kit. Xanthine oxidase activity.
  • the index was calculated according to the instruction manual.
  • the experimental data of each group were expressed as mean ⁇ standard deviation (x ⁇ s), statistical analysis was performed by SPSS 20.0 statistical software, and the difference between groups was tested by one-way variance test.

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Abstract

一种白凤菜总黄酮提取物，以重量百分含量计，含有80～85％的芦丁。药效实验结果表明，该提取物可以在一定程度上降低高尿酸血症模型小鼠肝脏内黄嘌呤氧化酶的活性、降低尿酸的合成，具有一定的降尿酸作用，可以作为潜在的治疗高尿酸血症或治疗痛风的药物；所述白凤菜总黄酮提取物的制备方法为，在提取步骤后，通过选择特定组成、特定配比的酶组成的复合酶进行酶解，进一步通过大孔树脂萃取浓缩和大孔树脂分离纯化步骤，使得制备得到的白凤菜总黄酮提取物中芦丁的HPLC纯度可达80～85％。

Description

一种白凤菜总黄酮提取物及其制备方法与治疗高尿酸血症的用途 技术领域
本发明属于药品或保健品领域，具体涉及一种白凤菜总黄酮提取物及其制备方法与治疗高尿酸血症的用途。
背景技术
痛风是嘌呤代谢紊乱和(或)尿酸排泄减少而致的血尿酸水平升高，单钠尿酸盐晶体在关节、软骨和肾脏等沉积所致的一种代谢性疾病。其主要表现为反复发作性关节红、肿、热、痛与功能障碍，甚至关节畸形、肾石病及尿酸性肾病。而尿酸排泄减少或生成增多所致的高尿酸血症是痛风的主要病因。高尿酸血症不仅是痛风的直接诱因，还与代谢综合征、Ⅱ型糖尿病、高血压、心血管疾病、慢性肾病等密切相关。高尿酸血症和痛风的发病机制与遗传因素、环境因素、糖原累积病、肾功能不全、血液病和药物等有关。
近年来，痛风及高尿酸血症的患病率逐年上升。流行病学研究表明，在中国，成人高尿酸血症的患病率为8.4％，且男性高于女性，分别为9.9％、7.0％；城市居民明显高于农村居民，分别为14.9％、6.6％；人均国内生产总值(GDP)水平较高的地区，高尿酸血症患病率也较高。
目前，用于抗高尿酸血症的药物主要有3大类：黄嘌呤氧化酶抑制剂、尿酸盐阴离子转运蛋白1(URAT1)抑制剂和尿酸氧化酶。临床上用于调节尿酸代谢的药物有别嘌呤醇、丙磺舒等，用于治疗急性痛风性关节炎的药物有秋水仙碱、非甾类抗炎药和糖皮质激素等。然而，这些药物有许多副作用，如：头疼、皮疹、水肿、胃肠出血、慢性肾乳头坏死及致死性超敏综合征等等，从而导致其在临床上的应用受到了很大程度的限制。
自古以来，中国、印度、加拿大等多个国家和地区就有用植物药治疗高 尿酸血症和痛风的传统。
白凤菜(Gynura formosana Kitam.)是菊科菊三七属多年生草本植物，又名白背天葵、片仔癀草，其含有丰富的维生素、生物碱类以及黄酮类物质，是一种药食两用的植物。研究表明，白凤菜主要用于肺炎、肺癌、肝炎、肝硬化、高血压等疾病的治疗，其还有解热解毒的功效。
目前，现有技术中尚没有白凤菜提取物可以用于治疗高尿酸血症的相关报道。
发明内容
为此，本发明提供一种白凤菜总黄酮提取物，进而提供其制备方法与用途。
为解决上述技术问题，本发明是通过以下技术方案来实现的：
本发明提供一种白凤菜总黄酮提取物，以重量百分含量计，含有80～85％的芦丁。
本发明还提供一种上述白凤菜总黄酮提取物的制备方法，包括以下步骤：
(1)提取：取白凤菜加入提取溶剂进行提取，调节提取液的pH值为4-8，得反应液；
(2)酶解：然后向反应液中加入复合酶进行酶解，30-50℃强制循环反应1-4小时，抽滤，收集滤液；
(3)萃取、浓缩：将滤液用大孔树脂A进行萃取，合并萃取液，将萃取液浓缩，得浓缩液；
(4)分离、纯化：将浓缩液离心，取上清液用大孔树脂B分离纯化，在波长为510nm下测定吸光度，收集洗脱液，浓缩、干燥，即得。
优选地，上述白凤菜总黄酮提取物的制备方法，所述酶解步骤中，采用 由木瓜蛋白酶、纤维素酶和果胶酶组成的复合酶进行酶解。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述复合酶与所述白凤菜的重量之比为：1:5～1:3。
进一步优选地，白凤菜总黄酮提取物的制备方法，所述复合酶中，木瓜蛋白酶、纤维素酶和果胶酶三者的重量比为(0.5-1.5)：(2-5)：(1-3)；
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述复合酶中，木瓜蛋白酶、纤维素酶和果胶酶三者的重量比为1：3：2。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，
所述大孔树脂A选自AB-8、DM-130、HZ841、ZH-00、ZH-01、ZH-02、ZH-03、CAD-40、CAD-45、BS-30中的至少一种；
所述大孔树脂B选自D-101、D-140、D-141、XAD-3、XAD-4、HP-20、HP-21、LD-605、LSA-10中的至少一种。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述提取步骤中，提取溶剂为水，所述白凤菜与所述水的重量之比为1：(20-60)。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述分离、纯化步骤中，洗脱溶剂为体积浓度为70-80％的乙醇水溶液，洗脱速度为3-15m/h。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述分离、纯化步骤中，洗脱溶剂为体积浓度为75％的乙醇水溶液，洗脱速度为5m/h。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述浓缩液中，白凤菜总黄酮的浓度为0.5mg/mL。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述萃取、浓缩步骤中，将滤液加入至盛有大孔树脂A的提取罐中，在30℃、80-150rpm下搅拌6-24小时，过滤，以大孔树脂A的重量计，取吸附后的大孔树脂A加入10-30重量倍量的体积浓度为70-95％的乙醇溶液，然后在30℃、80- 150rpm下搅拌6-24小时，过滤，即得萃取液。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述提取步骤中，采用盐酸或氢氧化钠调节提取液的pH值为4-8。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述干燥为冷冻干燥。
本发明还提供上述制备方法制备得到的白凤菜总黄酮提取物。
本发明还提供一种药物制剂，以上述白凤菜总黄酮提取物、或者上述制备方法制备得到的白凤菜总黄酮提取物为活性成分，按照常规工艺，加入常规辅料制成临床上可接受的片剂、胶囊剂、散剂、合剂、丸剂、颗粒剂、糖浆剂、贴膏剂、栓剂、气雾剂、软膏剂或注射剂。
所述常规辅料为：填充剂、崩解剂、润滑剂、助悬剂、粘合剂、甜味剂、矫味剂、防腐剂、基质等。填充剂包括：淀粉、预胶化淀粉、乳糖、甘露醇、甲壳素、微晶纤维素、蔗糖等；崩解剂包括：淀粉、预胶化淀粉、微晶纤维素、羧甲基淀粉钠、交联聚乙烯吡咯烷酮、低取代羟丙纤维素、交联羧甲基纤维素纳等；润滑剂包括：硬脂酸镁、十二烷基硫酸钠、滑石粉、二氧化硅等；助悬剂包括：聚乙烯吡咯烷酮、微晶纤维素、蔗糖、琼脂、羟丙基甲基纤维素等；粘合剂包括，淀粉浆、聚乙烯吡咯烷酮、羟丙基甲基纤维素等；甜味剂包括：糖精钠、阿斯帕坦、蔗糖、甜蜜素、甘草次酸等；矫味剂包括：甜味剂及各种香精；防腐剂包括：尼泊金类、苯甲酸、苯甲酸钠、山梨酸及其盐类、苯扎溴铵、醋酸氯乙定、桉叶油等；基质包括：PEG6000、PEG4000、虫蜡等。
本发明还提供上述白凤菜总黄酮提取物、上述制备方法制备得到的白凤菜总黄酮提取物、或者上述药物制剂在制备治疗高尿酸血症的药品或保健品中的应用。
本发明还提供上述白凤菜总黄酮提取物、上述制备方法制备得到的白凤菜总黄酮提取物、或者上述药物制剂在制备治疗痛风的药品或保健品中的应用。
本发明的技术方案具有如下优点：
(1)本发明提取分离得到一种含有80～85％的芦丁的白凤菜总黄酮提取物，药效实验结果表明，该提取物可以在一定程度上降低高尿酸血症模型小鼠肝脏内黄嘌呤氧化酶的活性、降低尿酸的合成，具有一定的降尿酸作用，可以作为潜在的治疗高尿酸血症或治疗痛风的药物；
(2)本发明白凤菜总黄酮提取物的制备方法，在提取步骤后，通过选择特定组成、特定配比的酶组成的复合酶在30-50℃下进行酶解，不仅避免了白凤菜总黄酮化合物的结构在高温下被破坏，而且使得白凤菜总黄酮化合物能够最大程度地被提取出来，进一步通过大孔树脂萃取浓缩和大孔树脂分离纯化步骤，使得白凤菜总黄酮化合物的提取率可达1.8％-2.0％，比现有方法中白凤菜总黄酮化合物的提取率提高可达30％以上，制备得到的白凤菜总黄酮提取物中芦丁的HPLC纯度可达80～85％。
附图说明
为了使本发明的内容更容易被清楚的理解，下面根据本发明的具体实施例并结合附图，对本发明作进一步详细的说明，其中：
图1是本发明实验例1中洗脱液的图谱；
图2是本发明实施例1制备的白凤菜总黄酮提取物的红外光谱图；
图3是本发明实施例1中芦丁对照品溶液的HPLC色谱图；
图4是本发明实施例1制备的白凤菜总黄酮提取物的HPLC色谱图。
具体实施方式
本发明以下实施例和实验例中，白凤菜采自福建省漳州市龙文区登科村，经鉴定为白凤菜。
实施例1
本实施例白凤菜总黄酮提取物按照以下方法制备而成：
(1)提取：取白凤菜100g，加入30重量倍量的水进行提取，用稀盐酸调节提取液的pH值为5，得反应液；
(2)酶解：然后向反应液中加入25g复合酶(该复合酶由重量比为1：3：2的木瓜蛋白酶、纤维素酶和果胶酶组成)进行酶解，40℃强制循环反应3小时，抽滤，收集滤液；
(3)萃取、浓缩：将滤液加入至盛有AB-8大孔树脂的提取罐中，在30℃、100rpm下搅拌12小时，过滤，以AB-8大孔树脂的重量计，取吸附后的AB-8大孔树脂加入20重量倍量的体积浓度为75％的乙醇溶液，然后在30℃、120rpm下搅拌12小时，过滤，即得萃取液，合并萃取液，将萃取液减压浓缩至白凤菜总黄酮的浓度为0.5mg/mL，得浓缩液；
(4)分离、纯化：将浓缩液10000rpm高速离心10分钟，取上清液加入装有大孔树脂D-101的层析柱内静止吸附60min，用体积浓度为75％的乙醇水溶液以5m/h的速度洗脱，在波长为510nm下测定吸光度，以吸光度值为纵坐标、以洗脱时间为横坐标作洗脱曲线图(其图谱如图1所示)，收集洗脱曲线中吸收峰范围内的洗脱液，浓缩、冷冻干燥，即得白凤菜总黄酮提取物。
经过计算，本实施例白凤菜总黄酮化合物的提取率为2.0％。
由图1可知，洗脱液在340min处出现一个明显的吸收峰，峰形较为单一，说明洗脱液中黄酮相对较纯。
A、本实施例白凤菜总黄酮提取物按照以下方法进行红外光谱鉴定：
取一定质量烘干后的芦丁标准品，以1：100加入烘干后的溴化钾，经研磨后制成固体压片，用傅立叶红外分光光度计在扫描范围4000-400cm -1、分辨率4、扫描次数为4的条件下绘制红外光谱图；同法绘制纯化后的白背天葵提取物的红外光谱图，对比鉴定。结果如图2所示。
由图2可知，芦丁标准品和白凤菜总黄酮提取物的红外光谱分别在3685.455～3018.177cm -1左右均出现宽而强的吸收峰，是-OH的伸缩振动峰，表明存在酚羟基或糖上的羟基，且数目较大；在2914.036cm -1处出现弱吸收峰，是碳氢键的伸缩振动峰，说明饱和碳上的氢较少；在1654.694cm -1处出现C＝O的伸缩振动中强峰，两者位置和峰型基本一致，说明提取物是黄酮类物质；在1371.88、1362.89cm -1处出现羟基的弯曲振动峰；在804.80、810.56cm -1处出现苯环邻位氢引起的吸收峰；在1010.07～696.62cm -1处出现苯环上取代基位置引起的吸收峰，但峰位置不同，说明提取物与芦丁的羟基取代位置不同；这些表明，提取物中含有羟基、羰基以及不同位置取代的苯环等官能团，特征吸收峰基本一致。因此可确定提取物是黄酮类化合物。
B、按照以下方法通过液相色谱分析本实施例白凤菜总黄酮提取物中的芦丁的含量:
B1、液相色谱条件的确定
液相色谱条件:保护柱:Eclipse XDB-C18 AnalyticalGuard Column(4.6×12.5mm，5μm)：ZOR BZX Eclipse XDB-C18(4.6×150mm，5μm)；流速：0.5mL/min；柱温：35℃；检测波长：368nm、254nm、210nm；进样体积：10μL；流动相:0.03％甲酸水溶液(A)，乙腈(B)；梯度洗脱程序如下：0～10min，20％B；10～12min，20％～24％B；12～20min，24％B；20～25min，24％～30％B；25～48min，30％B。
B2、对照品溶液的配置
准确称取芦丁0.001g，溶解于1mL甲醇中，制成1mg/mL的单一对照品溶液。并用一次性滤膜过滤，装入小试管中待用。
B3、测定
精密吸取对照品溶液、供试品溶液(实施例1制备的白凤菜黄酮提取物，配制成浓度为1μg/μL的甲醇溶液)，按照液相色谱检测条件分别进行检测分析。
对照品溶液的HPLC色谱图如图3所示，供试品溶液的HPLC色谱图如图4所示。
由图3可知，芦丁对照品溶液可在10分钟内完全分离，芦丁在本实验的色谱条件下，色谱基线基本平直，呈现色谱峰无拖尾现象，杂质也无干扰，且出峰较早，其保留时间为2.745min。
由图4，通过面积归一法计算可知，白凤菜提取物中芦丁的含量为81.29％。
实施例2
本实施例白凤菜总黄酮提取物按照以下方法制备而成：
(1)提取：取白凤菜100g，加入20重量倍量的水进行提取，用稀氢氧化钠溶液调节提取液的pH值为8，得反应液；
(2)酶解：然后向反应液中加入20g复合酶(该复合酶由重量比为0.5：5：1的木瓜蛋白酶、纤维素酶和果胶酶组成)进行酶解，30℃强制循环反应4小时，抽滤，收集滤液；
(3)萃取、浓缩：将滤液加入至盛有DM-130大孔树脂的提取罐中，在30℃、80rpm下搅拌24小时，过滤，取吸附后的DM-130大孔树脂加入10重量倍量的体积浓度为95％的乙醇溶液，然后在30℃、80rpm下搅拌24小时，过滤，即得萃取液，合并萃取液，将萃取液减压浓缩至白凤菜总黄酮的浓度为0.5mg/mL，得浓缩液；
(4)分离、纯化：将浓缩液6000rpm高速离心8分钟，取上清液加入装有大孔树脂HP-21的层析柱内静止吸附60min，用体积浓度为80％的乙醇水溶液以3m/h的速度洗脱，在波长为510nm下测定吸光度，以吸光度值为纵坐标、以洗脱时间为横坐标作洗脱曲线图，收集洗脱曲线中吸收峰范围内的洗脱液，浓缩、冷冻干燥，即得白凤菜总黄酮提取物。
经过计算，本实施例白凤菜总黄酮化合物的提取率为1.82％。
按照实施例1中“B项下”测定本实施例白凤菜总黄酮提取物中的芦丁。通过测定分析可知，HPLC图谱中，本实施例白凤菜总黄酮提取物中的芦丁含量为80％。
实施例3
本实施例白凤菜总黄酮提取物按照以下方法制备而成：
(1)提取：取白凤菜100g，加入60重量倍量的水进行提取，用稀盐酸调节提取液的pH值为4，得反应液；
(2)酶解：然后向反应液中加入32g复合酶(该复合酶由重量比为1.5：2：3的木瓜蛋白酶、纤维素酶和果胶酶组成)进行酶解，50℃强制循环反应1小时，抽滤，收集滤液；
(3)萃取、浓缩：将滤液加入至盛有ZH-01大孔树脂的提取罐中，在30℃、150rpm下搅拌6小时，过滤，取吸附后的ZH-01大孔树脂加入30重量倍量的体积浓度为70％的乙醇溶液，然后在30℃、150rpm下搅拌6小时，过滤，即得萃取液，合并萃取液，将萃取液减压浓缩至白凤菜总黄酮的浓度为0.5mg/mL，得浓缩液；
(4)分离、纯化：将浓缩液8000rpm高速离心5分钟，取上清液加入装有大孔树脂XAD-3的层析柱内静止吸附60min，用体积浓度为70％的乙醇水溶液以15m/h的速度洗脱，在波长为510nm下测定吸光度，以吸光度值为 纵坐标、以洗脱时间为横坐标作洗脱曲线图，收集洗脱曲线中吸收峰范围内的洗脱液，浓缩、冷冻干燥，即得白凤菜总黄酮提取物。
经过计算，本实施例白凤菜总黄酮化合物的提取率为1.91％。
按照实施例1中“B项下”测定本实施例白凤菜总黄酮提取物中的芦丁。通过测定分析可知，HPLC图谱中，本实施例白凤菜总黄酮提取物中的芦丁含量为85％。
实验例1 白凤菜总黄酮提取物抗痛风实验研究
1、实验目的
采用腹腔注射黄嘌呤致高尿酸血症模型的方式增加体内尿酸前体含量，使尿酸生成增多，造成小鼠高尿酸血症模型。通过给高尿酸血症小鼠灌胃白凤菜总黄酮提取物以小鼠血清中尿酸的抑制率、酸酐的抑制率和肝脏黄嘌呤氧化酶活性的抑制率为指标，探索白凤菜总黄酮提取物对高尿酸血症引起的痛风症状的影响。
2、实验材料
2.1实验动物
小鼠，清洁级，♂，体重28±2g，84只，购自吴氏动物中心。均饲养于空调室内，室温22±2℃，湿度(60±5)％，喂标准颗粒饲料，自由饮水和摄食。
2.2药物
白凤菜总黄酮提取物，别嘌呤醇片(合肥久联制药有限公司，批号：20140401)，痛风定片(长春海外制药，批号：1309105)；黄嘌呤(阿拉丁)；生理盐水；尿酸试剂盒(南京建成生物工程研究所，货号C012，生产批号：20140918)，黄嘌呤氧化酶试剂盒(南京建成生物工程研究所，货号A002，生产批号：20140210)；肌酐(Cr)测试盒(南京建成生物工程研究所，货号C011-1)。
2.3实验器材
低速离心机；微量移液枪；一次性注射器；毛细血管；表面皿；一次性离心管；手术剪；匀浆器。
3、实验方法
3.1供试药物
按照实施例1的方法制备白凤菜总黄酮提取物作为供试药物。
3.2痛风实验
3.2.1小鼠抗痛风实验
雄性昆明小鼠，84只，体重为28±2g，随机分为7组，分别为空白组、模型对照组、痛风定片组、别嘌呤醇组、白凤菜总黄酮提取物高、中、低剂量组。阳性组给予痛风定片(9.6mg/10g)和别嘌呤醇(0.2mL/10g)，白凤菜高、中、低剂量组分别按照24mg/10mL、12mg/10mL、6mg/10mL灌服白凤菜总黄酮提取物水溶液，模型对照物灌服等体积的生理盐水，连续11天，1次/天，
3.2.2血清中尿酸和肌酐指标
于末次给药1h后，将小鼠腹腔注射0.8％CMC-Na为溶剂配制的10％黄嘌呤。造模0.5h后，对小鼠进行摘眼球取血，取血后立即进行解剖并取下小鼠肝脏，并置于低温保存。取得的血液样品，3000r/min离心5min，取血清。按照试剂盒说明进行测定尿酸和肌酐。
3.2.3肝脏中黄嘌呤氧化酶(XOD)活性测定
采血后立即将小鼠处死，快速取出肝脏，称重，加入预冷至4℃的生理盐水制成10％的匀浆，于3000r/min离心10min，取上清液，按照试剂盒规定方法测定黄嘌呤氧化酶活性。
3.4数据统计分析
指标检测参照说明书进行计算，各组实验数据以均数±标准差(x±s)表示，SPSS 20.0统计学软件进行统计分析，组间差异用单因素方差检验。
4、实验结果
4.1小鼠血清尿酸和肌酐水平测定
白凤菜总黄酮提取物对小鼠血清尿酸水平的影响如表1所示。
表1 白凤菜总黄酮提取物对小鼠血清尿酸水平的影响(x±s)
组别 鼠数(n) 剂量g/10g 尿酸(mg/L) 肌酐(μmol/L)
空白组 12 - 20.57±4.92 0.023±0.004
模型组 12 - 40.46±3.36 ## 0.022±0.002
痛风定片 12 0.0096 27.53±1.53* 0.023±0.003
别嘌呤醇 12 0.0002 22.71±0.27** 0.023±0.001
白凤菜总黄酮提取物高剂量组 12 0.12 23.03±3.47** 0.020±0.002
白凤菜总黄酮提取物中剂量组 12 0.06 32.86±1.13* 0.017±0.000
白凤菜总黄酮提取物低剂量组 12 0.03 31.38±1.75* 0.019±0.001
注：与空白相比， #P<0.01， ##P<0.001；与模型组相比，*P<0.01，**P<0.001
由表1可知，(1)造模给药后，模型组血清尿酸水平明显增加，与空白组比较差异具有统计学意义(P<0.001)，表明模型建立成功；
(2)治疗给药后，白凤菜高、中、低三种剂量尿酸水平均有一定程度的降低，与模型组相比有明显的统计学差异(P<0.01)；各组对血清肌酐的含量均无明显差异。
4.2小鼠肝脏黄嘌呤氧化酶水平测定
白凤菜总黄酮提取物对小鼠血清尿酸水平的影响如表2所示。
表2 白凤菜总黄酮提取物对小鼠血清尿酸水平的影响(x±s)
组别 鼠数(n) XOD(U/gprot)
空白组 12 29.54±1.73
模型组 12 44.62±1.96 ##
痛风定片 12 40.64±1.33
别嘌呤醇 12 35.44±1.69**
白凤菜总黄酮提取物高剂量组 12 37.06±1.19*
白凤菜总黄酮提取物中剂量组 12 34.89±3.01**
白凤菜总黄酮提取物低剂量组 12 45.27±2.24
注：与空白相比， ##P<0.01；与模型组相比，*P<0.05，**P<0.01；
由表2可知，(1)与空白组相比，模型组差异具有显著性(P＜0.01)，说明造模成功；
(2)中剂量组和高剂量组肝脏黄嘌呤氧化酶活性明显低于模型组，差异具有显著性(P＜0.01，P＜0.05)，但是低剂量组与模型组相比无明显统计学差异；这表明，白凤菜中、高剂量组在一定程度上降低高尿酸血症模型小鼠肝脏内黄嘌呤氧化酶的活性、降低尿酸的合成，从而达到一定的降尿酸作用。
显然，上述实施例仅仅是为清楚地说明所作的举例，而并非对实施方式的限定。对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明创造的保护范围之中。

Claims (10)

  1. 一种白凤菜总黄酮提取物，其特征在于，以重量百分含量计，含有80～85％的芦丁。
  2. 一种权利要求1所述的白凤菜总黄酮提取物的制备方法，其特征在于，包括以下步骤：
    (1)提取：取白凤菜加入提取溶剂进行提取，调节提取液的pH值为4-8，得反应液；
    (2)酶解：然后向反应液中加入复合酶进行酶解，30-50℃强制循环反应1-4小时，抽滤，收集滤液；
    (3)萃取、浓缩：将滤液用大孔树脂A进行萃取，合并萃取液，将萃取液浓缩，得浓缩液；
    (4)分离、纯化：将浓缩液离心，取上清液用大孔树脂B分离纯化，在波长为510nm下测定吸光度，收集洗脱液，浓缩、干燥，即得。
  3. 根据权利要求2所述的白凤菜总黄酮提取物的制备方法，其特征在于，
    所述酶解步骤中，采用由木瓜蛋白酶、纤维素酶和果胶酶组成的复合酶进行酶解；
    所述复合酶与所述白凤菜的重量之比为：1:5～1:3。
  4. 根据权利要求2或3所述的白凤菜总黄酮提取物的制备方法，其特征在于，所述复合酶中，木瓜蛋白酶、纤维素酶和果胶酶三者的重量比为(0.5-1.5)：(2-5)：(1-3)。
  5. 根据权利要求4所述的白凤菜总黄酮提取物的制备方法，其特征在于，所述复合酶中，木瓜蛋白酶、纤维素酶和果胶酶三者的重量比为1：3： 2。
  6. 根据权利要求2-5任一项所述的白凤菜总黄酮提取物的制备方法，其特征在于，
    所述大孔树脂A选自AB-8、DM-130、HZ841、ZH-00、ZH-01、ZH-02、ZH-03、CAD-40、CAD-45、BS-30中的至少一种；
    所述大孔树脂B选自D-101、D-140、D-141、XAD-3、XAD-4、HP-20、HP-21、LD-605、LSA-10中的至少一种。
  7. 根据权利要求2-6任一项所述的白凤菜总黄酮提取物的制备方法，其特征在于，
    所述提取步骤中，提取溶剂为水，所述白凤菜与所述水的重量之比为1：(20-60)。
  8. 根据权利要求2-7任一项所述的白凤菜总黄酮提取物的制备方法，其特征在于，
    所述分离、纯化步骤中，洗脱溶剂为体积浓度为70-80％的乙醇水溶液，洗脱速度为3-15m/h；
    所述浓缩液中，白凤菜总黄酮的浓度为0.5mg/mL。
  9. 一种药物制剂，其特征在于，以权利要求1所述的白凤菜总黄酮提取物、或者权利要求2-8任一项所述的制备方法制备得到的白凤菜总黄酮提取物为活性成分，按照常规工艺，加入常规辅料制成临床上可接受的片剂、胶囊剂、散剂、合剂、丸剂、颗粒剂、糖浆剂、贴膏剂、栓剂、气雾剂、软膏剂或注射剂。
  10. 权利要求1所述的白凤菜总黄酮提取物、权利要求2-8任一项所述的制备方法制备得到的白凤菜总黄酮提取物、或者权利要求9所述的药物制剂在制备治疗高尿酸血症或治疗痛风的药品或保健品中的应用。
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111141855A (zh) * 2020-01-17 2020-05-12 南京嘉晨医药科技有限公司 一种对乙酰半胱氨酸口服溶液中甜蜜素的检测方法
CN113219074A (zh) * 2019-12-31 2021-08-06 上海黄海制药有限责任公司 一种HPLC-MS/MS法测定犬血浆中Rutin和Ombuoside的浓度的方法
CN113866325A (zh) * 2021-09-14 2021-12-31 马鞍山市产品质量监督检验所 一种绿色环保型测定饮料中多种添加剂的分析方法

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107582588A (zh) * 2017-09-18 2018-01-16 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与治疗酒精性脂肪肝的用途
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CN107582589A (zh) 2017-09-18 2018-01-16 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与治疗高尿酸血症的用途
CN115120604A (zh) * 2021-03-24 2022-09-30 陕西凤丹正元生物科技有限公司 芹菜素7-o-葡萄糖苷作为降尿酸和痛风性关节炎制剂的应用
CN114617923B (zh) * 2022-04-14 2022-09-20 中国海洋大学 一种抑制尿酸盐转运蛋白1的甘松提取物及其制备方法与应用

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104173458A (zh) * 2014-08-27 2014-12-03 漳州片仔癀药业股份有限公司 一种具有防治高尿酸血症作用的中药组合物及其制备方法
CN107582588A (zh) * 2017-09-18 2018-01-16 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与治疗酒精性脂肪肝的用途
CN107582590A (zh) * 2017-09-18 2018-01-16 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与治疗急性咽炎的用途
CN107582589A (zh) * 2017-09-18 2018-01-16 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与治疗高尿酸血症的用途
CN107582587A (zh) * 2017-09-18 2018-01-16 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与治疗非酒精性脂肪肝的用途
CN107625800A (zh) * 2017-09-18 2018-01-26 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与抗炎镇痛的用途

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003171283A (ja) * 2001-12-05 2003-06-17 Fancl Corp キサンチンオキシダーゼ阻害剤
CN1239164C (zh) * 2003-06-20 2006-02-01 薛秀芳 山楂叶有效部位及提取方法和应用
JP4790561B2 (ja) * 2006-10-12 2011-10-12 東洋精糖株式会社 フラボノイド組成物、その製造方法および用途
CN101336949B (zh) * 2008-08-21 2010-12-08 中国食品发酵工业研究院 从白子菜中提取多糖和黄酮的方法
CN103230444B (zh) * 2013-05-15 2014-03-19 李伟权 一种降脂护肝中药组合物及其制备方法和应用
TWI558403B (zh) * 2013-06-04 2016-11-21 中央研究院 富含半乳糖脂之植物萃取物及其用途
CN104013659B (zh) * 2014-06-09 2017-02-15 新疆生命核力高科股份有限公司 一种提纯的雪菊黄酮片剂及其制备方法
CN104151380A (zh) * 2014-06-22 2014-11-19 北京安德益源生物科技有限公司 一种高纯度芦丁的制备方法
CN104825517A (zh) * 2015-05-07 2015-08-12 李伟权 白子菜在制备治疗痛风性关节炎的药物中的应用
CN106038415A (zh) * 2016-07-12 2016-10-26 广州丹奇日用化工厂有限公司 一种含有白凤菜提取物的化妆品组合物

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104173458A (zh) * 2014-08-27 2014-12-03 漳州片仔癀药业股份有限公司 一种具有防治高尿酸血症作用的中药组合物及其制备方法
CN107582588A (zh) * 2017-09-18 2018-01-16 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与治疗酒精性脂肪肝的用途
CN107582590A (zh) * 2017-09-18 2018-01-16 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与治疗急性咽炎的用途
CN107582589A (zh) * 2017-09-18 2018-01-16 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与治疗高尿酸血症的用途
CN107582587A (zh) * 2017-09-18 2018-01-16 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与治疗非酒精性脂肪肝的用途
CN107625800A (zh) * 2017-09-18 2018-01-26 漳州片仔癀药业股份有限公司 一种白凤菜总黄酮提取物及其制备方法与抗炎镇痛的用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LIN, YANYAN ET AL.: "Optimization the extraction of total flavonoids from Gynua formosana Kitam guided by ultrasound and research on its antibacterial activity in vitro", JOURNAL OF YOUJIANG MEDICAL UNIVERSITY FOR NATIONALITIES, vol. 39, no. 2, 30 April 2017 (2017-04-30), pages 90 - 93, ISSN: 1001-5817 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113219074A (zh) * 2019-12-31 2021-08-06 上海黄海制药有限责任公司 一种HPLC-MS/MS法测定犬血浆中Rutin和Ombuoside的浓度的方法
CN111141855A (zh) * 2020-01-17 2020-05-12 南京嘉晨医药科技有限公司 一种对乙酰半胱氨酸口服溶液中甜蜜素的检测方法
CN111141855B (zh) * 2020-01-17 2022-05-17 南京嘉晨医药科技有限公司 一种对乙酰半胱氨酸口服溶液中甜蜜素的检测方法
CN113866325A (zh) * 2021-09-14 2021-12-31 马鞍山市产品质量监督检验所 一种绿色环保型测定饮料中多种添加剂的分析方法
CN113866325B (zh) * 2021-09-14 2023-05-05 马鞍山市产品质量监督检验所 一种测定饮料中多种添加剂的分析方法

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