CN108379455A - 一种降尿酸组合物 - Google Patents
一种降尿酸组合物 Download PDFInfo
- Publication number
- CN108379455A CN108379455A CN201810477623.6A CN201810477623A CN108379455A CN 108379455 A CN108379455 A CN 108379455A CN 201810477623 A CN201810477623 A CN 201810477623A CN 108379455 A CN108379455 A CN 108379455A
- Authority
- CN
- China
- Prior art keywords
- alcohol extracting
- trioxypurine
- composition
- sweet potato
- extracting thing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 72
- 239000000284 extract Substances 0.000 claims abstract description 40
- 244000017020 Ipomoea batatas Species 0.000 claims abstract description 29
- 235000002678 Ipomoea batatas Nutrition 0.000 claims abstract description 29
- 241000719837 Anoectochilus Species 0.000 claims abstract description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229940079593 drug Drugs 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 8
- 239000000470 constituent Substances 0.000 claims 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 abstract description 28
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 abstract description 27
- 229940116269 uric acid Drugs 0.000 abstract description 27
- 230000000694 effects Effects 0.000 abstract description 25
- 201000005569 Gout Diseases 0.000 abstract description 9
- 230000029142 excretion Effects 0.000 abstract description 5
- 230000003907 kidney function Effects 0.000 abstract description 4
- 241001465754 Metazoa Species 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 2
- 235000019441 ethanol Nutrition 0.000 description 33
- 241000699666 Mus <mouse, genus> Species 0.000 description 29
- 201000001431 Hyperuricemia Diseases 0.000 description 25
- 108010093894 Xanthine oxidase Proteins 0.000 description 24
- 102100033220 Xanthine oxidase Human genes 0.000 description 24
- 238000003304 gavage Methods 0.000 description 16
- 210000002966 serum Anatomy 0.000 description 14
- 239000000243 solution Substances 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 239000013641 positive control Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- IAPCTXZQXAVYNG-UHFFFAOYSA-M Potassium 2,6-dihydroxytriazinecarboxylate Chemical compound [K+].[O-]C(=O)C1=NC(=O)NC(=O)N1 IAPCTXZQXAVYNG-UHFFFAOYSA-M 0.000 description 5
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 5
- 229960003459 allopurinol Drugs 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 229950000193 oteracil Drugs 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000000287 crude extract Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 229940109239 creatinine Drugs 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000005252 bulbus oculi Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000000469 ethanolic extract Substances 0.000 description 2
- -1 flavone compound Chemical class 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000000913 Kidney Calculi Diseases 0.000 description 1
- 206010048469 Kidney enlargement Diseases 0.000 description 1
- 101000781528 Mus musculus Xanthine oxidase Proteins 0.000 description 1
- UHJOFHKUHLWIMU-UHFFFAOYSA-N N1CCNCC1.[O] Chemical compound N1CCNCC1.[O] UHJOFHKUHLWIMU-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029148 Nephrolithiasis Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 108010092464 Urate Oxidase Proteins 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 208000026816 acute arthritis Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002961 anti-hyperuricemic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000005133 heliotropism Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000003716 rejuvenation Effects 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
Classifications
-
- 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)
- A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
-
- 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)
-
- 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)
- A61K36/39—Convolvulaceae (Morning-glory family), e.g. bindweed
-
- 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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/898—Orchidaceae (Orchid family)
-
- 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
-
- 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
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- 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
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明公开了一种降尿酸组合物，它由油菜花粉醇提取物、紫薯醇提取物、金线莲水提取物组成。体内动物实验结果表明：本发明具有降尿酸、恢复肾功能、加速尿酸排泄、减少尿酸生成等作用，是一种疗效显著，安全性高的降尿酸和治疗痛风药物。
Description
技术领域
本发明属于制药领域，涉及一种降尿酸组合物。
背景技术
痛风是由于嘌呤代谢紊乱和(或)尿酸排泄障碍所导致的一组代谢性疾病，尿酸盐沉积在关节部位可诱发痛风性急性关节炎反复发作、痛风石沉积和关节畸形等。严重的痛风患者其肾脏也会受到损害，如引起尿酸肾结石和慢性间质性肾炎等。高尿酸血症是痛风发生的主要生化基础，是继高血压、高血糖、高血脂后的“第四高”，严重危害着人类的健康。许多研究表明，高尿酸血症与糖尿病、高血压、肥胖、冠心病、慢性肾脏疾病等都有密切关系。最新的流行病学调查结果显示，近年来随着人们生活水平的提高、生活方式和饮食结构的改变，高尿酸血症和痛风的发病率呈现持续增加的趋势，且发病人群趋于年轻化，因此，寻找和研发防治痛风和高尿酸血症的药物已越来越重要。
目前，对于高尿酸血症和痛风的预防一般是控制高嘌呤食物和肉类的摄入、增加果蔬的摄入、限制饮酒以及增强运动等。仅仅通过膳食干预，还不能从根本上解决尿酸代谢异常问题。对于高尿酸血症的治疗，使用的药物大都会呈现出不同程度的毒副作用。因此，从天然产物中筛选高效、安全无毒的降尿酸药物已逐渐成为研究的新方向。
油菜花粉中含有黄酮类化合物、类胡萝卜素、甾醇以及亚精胺类化合物等多种生物活性物质，因而具有广泛的生物功效，如抗氧化、抗炎、抗辐射、抑制肿瘤、调节免疫、抑菌、调节血脂等。目前国内外没有对油菜花粉提取物干预高尿酸血症的相关文献报道。
有文献报导，紫薯能够抑制黄嘌呤氧化酶活性，从而对高尿酸血症小鼠起到降尿酸的作用，同时还能加大体内尿酸的排泄量，减少高尿酸血症导致的肾功能损伤，改善肾小管扩张及间质纤维化现象。研究还表明，金线莲可有效改善高尿酸血症小鼠的肾脏功能，可加速尿酸的排泄，对痛风和高尿酸血症具有一定的预防和治疗作用。但是目前还没有组合以后治疗痛风的相关文献。
发明内容
本发明的目的是提供一种降尿酸组合物，在本申请人前期对油菜花粉醇提取物降尿酸的研究成果基础上，通过将油菜花粉醇提取物与紫薯醇提取物、金线莲水提取物组合，以进一步提高疗效。
本发明提供的降尿酸组合物，它由油菜花粉醇提取物、紫薯醇提取物、金线莲水提取物组成。
优选地，所述油菜花粉醇提取物、紫薯醇提取物、金线莲水提取物的重量比为(2-8)：(2-8)：(5-15)。
进一步优选地，所述油菜花粉醇提取物、紫薯醇提取物、金线莲水提取物的重量比为5：5：10。
所述油菜花粉醇提取物，指的是油菜花粉的乙醇提取物，优选50-90％乙醇，最佳是75％乙醇。将油菜花粉用乙醇进行提取，将提取液浓缩干燥后即可得到。当然，为了进一步提高疗效，降低副作用，减少服用剂量，还可以将提取物继续进行除杂精制处理，例如采用聚酰胺柱或大孔吸附树脂柱进行除杂精制处理。
所述紫薯醇提取物，指的是紫薯的乙醇提取物，优选50-90％乙醇，最佳是60％乙醇。将紫薯用乙醇进行提取，将提取液浓缩干燥后即可得到。当然，为了进一步提高疗效，降低副作用，减少服用剂量，还可以将提取物继续进行除杂精制处理，例如采用大孔吸附树脂柱进行除杂精制处理。
所述金线莲水提取物是将金线莲用水提取，提取液浓缩干燥后得到。
本发明中所涉及到的乙醇浓度，均为体积浓度，如50％乙醇，指的是每100ml乙醇水溶液中，含有乙醇50ml。
体外黄嘌呤氧化酶抑制实验结果表明：本发明组合物对黄嘌呤氧化酶有较强的抑制作用，IC50值达到了0.17mg/mL，抑制效果均低于三种单味提取物，表明将三种提取物组合后，对黄嘌呤氧化酶的抑制体现出协同增效。
体内动物实验结果表明：(1)与单味提取物相比，本发明组合物具有更强的降尿酸效果；与常用的降尿酸药物别嘌呤醇相比，本发明组合物降尿酸作用更加温和，更加安全。
(2)本发明组合物不会造成肝肾损伤，并能降低高尿酸血症小鼠的BUN和Cr值，从而有利于恢复肾功能，加速尿酸的排泄。与单味提取物相比，降低幅度更加明显；与别嘌呤醇相比，降低后的BUN和Cr值更接近于正常值，因此更加安全。
(3)本发明组合物能抑制高尿酸血症小鼠体内的黄嘌呤氧化酶活性，从而减少尿酸的生成，且与单味提取物相比，降低幅度更加明显。
综上，本发明提供的组合物可用于降尿酸和治疗痛风，且疗效显著，安全性高。
具体实施方式
实施例1
(1)油菜花粉醇提取物的制备
取经破壁处理后的油菜花粉，用75％乙醇进行提取，将提取液减压浓缩至无乙醇时为止；将提取液用水饱和的正丁醇萃取，直至正丁醇层无色为止，减压浓缩正丁醇层并真空冷冻干燥，得到油菜花粉粗提取物；将粗提取物用水溶解后上AB-8型大孔吸附树脂柱，先用水冲洗至洗脱液不浑浊为止，然后用50％乙醇洗脱，收集乙醇洗脱液，经减压浓缩，真空冷冻干燥后得到油菜花粉提取物。
(2)紫薯醇提取物的制备
将紫薯粉用60％乙醇浸提，将提取液减压浓缩至无乙醇时为止；将提取液用水饱和的乙酸乙酯萃取，直至乙酸乙酯层无色为止，减压浓缩乙酸乙酯层并真空冷冻干燥，得到紫薯粗提取物；将粗提取物用水溶解后上AB-8大孔吸附树脂柱，用pH＝3的无水乙醇/磷酸盐缓冲液作为洗脱剂进行洗脱，收集洗脱液，浓缩，干燥后得到紫薯提取物。
(3)金线莲水提取物的制备
将金线莲加水浸泡30分钟，再煎煮2次，每次60分钟，过滤后将滤液在60℃下减压浓缩得到浓缩液，将浓缩液干燥即得金线莲提取物。
(4)组合物的制备
将油菜花粉醇提取物、紫薯醇提取物、金线莲水提取物以1:1:2的重量比例混合均匀即得。
实施例2组合物对XO的抑制作用
(1)试验方法
黄嘌呤氧化酶(XO)催化黄嘌呤(Xan)产生尿酸并在290nm处有特征吸收峰，采用紫外分光光度计的动力学/时间软件每隔15s测定一次吸光度，共测定20次，在这段时间内吸光度随时间呈线性增加，其斜率即为酶的反应速率。斜率越大，说明酶的活力越强。
首先将实施例1制备的油菜花粉醇提取物、紫薯醇提取物、金线莲水提取物及组合物分别溶解于1％DMSO中配制成不同浓度的样品溶液，然后移取100μL 7.5×10-8mol/L XO溶液和50μL样品溶液混合，37℃孵育5min后加入100μL的底物溶液Xan(5×10-5mol/L)启动反应，测定290nm波长下的吸光度变化并计算斜率R。以相同体积的0.05mol/L磷酸盐缓冲溶液(pH＝7.5)代替样品作为空白对照，记录其吸光度的变化并计算斜率R0。黄嘌呤氧化酶的相对活性(％)＝R/R0×100％。同时通过SPSS 13.0软件分别计算不同提取物的IC50值。
(2)实验结果
结果显示不同提取物对XO酶均有抑制作用且呈现一定的浓度依赖关系，即随着样品浓度的增加，XO的相对活性不断降低。组合物相比于其它单一提取物在浓度0～0.32mg/mL范围内均有最低的XO相对活性，说明组合物对XO具有更强的抑制作用。表1显示了不同提取物对XO的IC50值，其中组合物对XO的IC50值最低，由此也说明组合物抑制XO活性最强。
表1不同提取物和组合物对XO的IC50值(n＝4)
| 样品 | IC50值(mg/mL) |
| 油菜花粉醇提取物 | 0.22±0.02 |
| 紫薯醇提取物 | 0.20±0.03 |
| 金线莲水提取物 | 0.20±0.06 |
| 组合物 | 0.17±0.02 |
实施例3组合物降尿酸效果评价
(1)试验方法
采用尿酸酶抑制剂氧嗪酸钾诱导建立高尿酸血症小鼠模型，首先将昆明雄性小鼠随机分为7组，分别为：空白对照组，模型组，油菜花粉醇提取物组(200mg/kg·bw)，紫薯醇提取物组(200mg/kg·bw)、金线莲水提取物组(200mg/kg·bw)、组合物组(200mg/kg·bw)、别嘌呤醇阳性对照组(5mg/kg·bw)，每组10只小鼠。在保证正常饮食饮水的条件下，将氧嗪酸钾/羧甲基纤维素钠混悬液按250mg/kg·d的剂量对模型组小鼠连续灌胃7天，建立小鼠高尿酸血症动物模型。空白对照组小鼠灌胃同等浓度的CMC-Na溶液。在当天结束氧嗪酸钾混悬液灌胃1h后，向阳性组小鼠灌胃5mg/kg的别嘌呤醇溶液，各实验组小鼠分别灌胃油菜花粉醇提取物、紫薯醇提取物、金线莲水提取物、组合物的水溶液，空白对照组、模型组灌胃蒸馏水。灌胃前1h对小鼠进行禁食处理。第6日结束灌胃后对小鼠处以12h禁食处理，以便第7天灌胃结束后进行检测样品的提取工作。
①脏器指数的测定
在第7天灌胃前12小时对所有小鼠进行断粮。称量小鼠的体重，在第7天灌胃结束后，摘眼球取血，断颈处死小鼠。取出其肝脏、肾脏组织，在4℃预冷的生理盐水中漂洗干净后称重，并计算脏器指数。
②小鼠血清尿酸(UA)、尿素氮(BUN)、肌酐(Cr)含量的测定
连续灌胃7天后摘眼球取血，断颈处死小鼠。血液在室温条件下自然凝血1h后于4℃温度下3500rpm离心10min，取其上清液即得血清，将血清分装后放置于-20℃冷冻保存，备用。采用尿酸(UA)测试盒、尿素氮(BUN)测试盒及肌酐(Cr)测试盒来测定小鼠血清UA、BUN及Cr的含量。
③小鼠肝脏匀浆中黄嘌呤氧化酶(XO)活性的测定
取各组小鼠的肝脏样本，加入4℃预冷过的生理盐水，按照质量比1：9的比例制成10％的肝脏组织匀浆，在4℃4000r/min条件下离心10min后，轻轻吸掉表面脂肪组织后，缓慢吸取上清液，使用上清液，采用总蛋白(TP)测试盒测定肝脏组织匀浆中的总蛋白含量，并采用黄嘌呤氧化酶(XO)测试盒来测定小鼠肝脏组织匀浆中XO活性。
(2)实验结果
①对高尿酸血症小鼠的降尿酸作用
各组小鼠的血清UA值如表2所示，与空白组相比，氧嗪酸钾介导的模型组小鼠其血尿酸值明显增加(p<0.001)，而在灌胃各提取物及其组合物后，小鼠的血尿酸水平均有不同程度降低，其中组合物降幅较大。而阳性对照组的小鼠在灌胃别嘌呤醇后显示出了极显著的抑制尿酸作用，表明别嘌呤醇降低血清UA能力过强，可能会产生一定的副作用。相比之下，本发明提供的组合物不仅降血清UA的效果较好，而且作用更加温和。
表2不同提取物和组合物对高尿酸血症小鼠血清UA值的影响(n＝10)
| 样品 | 血清UA值(μmol/L) |
| 空白组 | 50.50±0.01 |
| 模型组 | 91.92±0.06 |
| 阳性对照组 | 6.25±0.05 |
| 油菜花粉醇提取物组 | 52.24±0.03 |
| 紫薯醇提取物组 | 55.37±0.03 |
| 金线莲水提取物组 | 52.25±0.04 |
| 组合物组 | 48.70±0.07 |
②对高尿酸血症小鼠肾功能改善的作用
在动物实验各项指标当中，脏器指数可以直观地显示出动物脏器的健康状况，以表征其毒性作用。从试验结果来看，氧嗪酸钾介导的高尿酸血症小鼠在经7天药物灌胃后的体重，肝脏、肾脏的质量及其相关脏器指数与空白组相比均未表现出明显的显著性差异，表明各提取物及其组合物灌胃时并未给小鼠的肝脏及肾脏带来明显的器官损伤。
高尿酸血症小鼠在经过7天药物灌胃后其血清中的尿素氮(BUN)和肌酐(Cr)水平如表3所示。与空白组相比，模型组的BUN和Cr值均出现明显增高(p<0.01)的异常现象，说明其肾脏的功能性有所下降。而阳性对照组、各提取物及其组合物组的BUN和Cr值均出现不同程度下降，其中组合物组的BUN和Cr值下降幅度较大，且最接近于正常值。
表3不同提取物和组合物对高尿酸血症小鼠BUN和Cr值的影响(n＝10)
| 样品 | BUN(mmol/L) | Cr(μmol/L) |
| 空白组 | 7.45±0.07 | 13.97±0.04 |
| 模型组 | 10.37±0.01 | 22.54±0.07 |
| 阳性对照组 | 7.21±0.04 | 10.25±0.02 |
| 油菜花粉醇提取物组 | 8.46±0.01 | 16.72±0.02 |
| 紫薯醇提取物组 | 7.97±0.03 | 15.55±0.03 |
| 金线莲水提取物组 | 8.20±0.03 | 16.89±0.04 |
| 组合物组 | 7.68±0.05 | 14.58±0.03 |
③对高尿酸血症小鼠体内XO抑制作用
如表4所示，在灌胃氧嗪酸钾混悬液进行造模之后，模型组小鼠肝脏中的黄嘌呤氧化酶水平与空白组相比显著上升(p<0.001)，达到2.67U/g。而阳性对照组、各提取物及其组合物组的XO活性均出现不同程度下降，其中组合物组的XO活性值下降幅度较大，且最接近于正常值。
表4不同提取物和组合物对高尿酸血症小鼠黄嘌呤氧化酶水平的影响(n＝10)
实施例4不同比例的组合物对高尿酸血症小鼠的降尿酸作用
分别按油菜花粉醇提取物组：紫薯醇提取物组：金线莲水提取物组＝1:1:2、1:2:1、2:1:1、1:1:1的比例制备组合物，按实施例3中的试验方法考察组合物对高尿酸血症小鼠血清尿酸(UA)的影响，如表5所示。结果表明：当油菜花粉醇提取物：紫薯醇提取物：金线莲水提取物为1:1:2时降尿酸效果最好。
表5不同比例组合物对高尿酸血症小鼠血清UA值的影响(n＝10)
| 样品 | 血清UA值(μmol/L) |
| 空白组 | 50.50±0.03 |
| 模型组 | 91.92±0.04 |
| 阳性对照组 | 6.25±0.04 |
| 油菜：紫薯：金线莲＝1:1:2 | 46.30±0.06 |
| 油菜：紫薯：金线莲＝1:2:1 | 52.50±0.05 |
| 油菜：紫薯：金线莲＝2:1:1 | 57.50±0.02 |
| 油菜：紫薯：金线莲＝1:1:1 | 51.30±0.03 |
Claims (4)
1.一种降尿酸组合物，其特征在于由油菜花粉醇提取物、紫薯醇提取物、金线莲水提取物组成。
2.如权利要求1所述的降尿酸组合物，其特征在于：所述油菜花粉醇提取物、紫薯醇提取物、金线莲水提取物的重量比为(2-8)：(2-8)：(5-15)。
3.如权利要求2所述的降尿酸组合物，其特征在于：所述油菜花粉醇提取物、紫薯醇提取物、金线莲水提取物的重量比为5：5：10。
4.一种降尿酸药物，它的活性成分是权利要求1-3任何一项所述的组合物。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810477623.6A CN108379455B (zh) | 2018-05-18 | 2018-05-18 | 一种降尿酸组合物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810477623.6A CN108379455B (zh) | 2018-05-18 | 2018-05-18 | 一种降尿酸组合物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108379455A true CN108379455A (zh) | 2018-08-10 |
| CN108379455B CN108379455B (zh) | 2021-01-29 |
Family
ID=63071253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810477623.6A Active CN108379455B (zh) | 2018-05-18 | 2018-05-18 | 一种降尿酸组合物 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108379455B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113456661A (zh) * | 2021-08-06 | 2021-10-01 | 华中农业大学 | 一种降尿酸的复合多糖组合物及其应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100759468B1 (ko) * | 2006-06-26 | 2007-10-04 | 한국생명공학연구원 | 자색 고구마로부터 분리된 자색 색소를 함유하는 통풍 예방및 치료용 조성물 |
| CN104970178A (zh) * | 2015-07-31 | 2015-10-14 | 武杰 | 一种金线莲保健冰淇淋及其生产方法 |
| CN105495214A (zh) * | 2015-12-21 | 2016-04-20 | 武杰 | 一种金线莲草莓汁饮料及其制作方法 |
| CN105942082A (zh) * | 2016-04-29 | 2016-09-21 | 长泰县吉泰食品技术研发中心 | 一种金线莲饮料及其生产工艺 |
-
2018
- 2018-05-18 CN CN201810477623.6A patent/CN108379455B/zh active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100759468B1 (ko) * | 2006-06-26 | 2007-10-04 | 한국생명공학연구원 | 자색 고구마로부터 분리된 자색 색소를 함유하는 통풍 예방및 치료용 조성물 |
| CN104970178A (zh) * | 2015-07-31 | 2015-10-14 | 武杰 | 一种金线莲保健冰淇淋及其生产方法 |
| CN105495214A (zh) * | 2015-12-21 | 2016-04-20 | 武杰 | 一种金线莲草莓汁饮料及其制作方法 |
| CN105942082A (zh) * | 2016-04-29 | 2016-09-21 | 长泰县吉泰食品技术研发中心 | 一种金线莲饮料及其生产工艺 |
Non-Patent Citations (4)
| Title |
|---|
| ZHANG ZI-CHENG等: "Effects of anthocyanins from purple sweet potato (Ipomoea batatas L. cultivar Eshu No. 8) on the serum uric acid level and xanthine oxidase activity in hyperuricemic mice", 《FOOD & FUNCTION》 * |
| 王冲: "《功能医学临床实践》", 31 May 2017, 西安交通大学出版社 * |
| 许光辉等: "金线莲提取物对黄嘌呤氧化酶活性及高尿酸血症小鼠的影响", 《海峡药学》 * |
| 陈小权: "油菜花粉超微粉对肉鸡促长及保健作用机理研究", 《中国优秀硕士学位论文全文数据库 农业科技辑》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113456661A (zh) * | 2021-08-06 | 2021-10-01 | 华中农业大学 | 一种降尿酸的复合多糖组合物及其应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108379455B (zh) | 2021-01-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103327992A (zh) | 用于预防或治疗炎性疾病的包含络石藤提取物和牡丹皮提取物的药物组合物以及制备该药物组合物的方法 | |
| CN1267456C (zh) | 一种降糖的沙蒿多糖制备方法及其应用 | |
| CN104922176B (zh) | 一种野菊花提取物的应用 | |
| CN109939143A (zh) | 一种用于降血糖控制并发症的中药组合物及其制备方法 | |
| KR20160007728A (ko) | 마늘껍질 추출물의 제조방법 및 이를 이용하여 제조된 당뇨 예방 및 개선용 식품 조성물 | |
| JP5622222B2 (ja) | 血脂降下組成物及びその使用 | |
| CN108379455A (zh) | 一种降尿酸组合物 | |
| CN113615756A (zh) | 一种复配普洱茶功能组合物的制备方法和用途 | |
| Syahrina et al. | Phytochemical screening and anti-hyperuricemia activity test in vivo of ethanolic extract of shallot (Allium cepa L.) skin | |
| CN117717575A (zh) | 一种紫苏叶提取物及其制备方法与应用 | |
| JP4602674B2 (ja) | マルターゼ阻害剤 | |
| KR101710780B1 (ko) | 백출 추출물을 포함하는 비만 또는 지질 관련 대사성 질환의 예방 또는 치료용 약학적 조성물 | |
| TWI725317B (zh) | 新穿心蓮內酯之組成物用於血糖調降之應用 | |
| CN102596214B (zh) | 改善脂肪肝的组合物 | |
| CN113456661B (zh) | 一种降尿酸的复合多糖组合物及其应用 | |
| WO2018151334A1 (ja) | キサンチンオキシダーゼ阻害剤及びその製造方法 | |
| CN108392509B (zh) | 一种油菜花粉提取物及其用途 | |
| CN105920051B (zh) | 一种金针菇提取物及其制备方法与应用 | |
| CN107753669A (zh) | 一种具有降尿酸作用的药物组合物及其制备方法与用途 | |
| JP7062433B2 (ja) | キトサンとアンペロプシンを含有する血中尿酸値低減用組成物 | |
| Abigail et al. | Assessment of antihyperglycemic effect of nut fractions of vigna Subterranea on streptozotocin-induced diabetic rats | |
| CN106333202A (zh) | 一种大麦若叶组合物 | |
| CN108524574A (zh) | 一种神农香菊提取物及应用 | |
| TWI766295B (zh) | 一種草本組合物及其降尿酸、降低體脂肪及降低血糖之用途 | |
| US11318153B2 (en) | Method of using Neoandrographolide for lowering blood sugar, lowering blood lipid, improving liver function and improving renal function |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20211112 Address after: 430000 room D003, building B8, biological innovation park, No. 666, Gaoxin Avenue, Donghu New Technology Development Zone, Wuhan City, Hubei Province Patentee after: Wuhan Huayu Xinmei fungus industry Co., Ltd Address before: 430070 No. 1, Shizishan street, Hongshan District, Wuhan City, Hubei Province Patentee before: Huazhong Agricultural University |