CN108524668A - 一种对药物性肝损伤具有修复和治疗作用的枸杞提取物的制备方法 - Google Patents
一种对药物性肝损伤具有修复和治疗作用的枸杞提取物的制备方法 Download PDFInfo
- Publication number
- CN108524668A CN108524668A CN201810522804.6A CN201810522804A CN108524668A CN 108524668 A CN108524668 A CN 108524668A CN 201810522804 A CN201810522804 A CN 201810522804A CN 108524668 A CN108524668 A CN 108524668A
- Authority
- CN
- China
- Prior art keywords
- hepatic injury
- fruit extract
- reparation
- therapeutic effect
- wolfberry fruit
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 53
- 229940079593 drug Drugs 0.000 title claims abstract description 43
- 235000015468 Lycium chinense Nutrition 0.000 title claims abstract description 35
- 235000013399 edible fruits Nutrition 0.000 title claims abstract description 35
- 235000015459 Lycium barbarum Nutrition 0.000 title claims abstract description 34
- 231100000753 hepatic injury Toxicity 0.000 title claims abstract description 34
- 239000000284 extract Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 16
- 244000241838 Lycium barbarum Species 0.000 title claims description 23
- 239000011347 resin Substances 0.000 claims abstract description 29
- 229920005989 resin Polymers 0.000 claims abstract description 29
- 244000241872 Lycium chinense Species 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000007788 liquid Substances 0.000 claims abstract description 14
- 239000002250 absorbent Substances 0.000 claims abstract description 13
- 230000002745 absorbent Effects 0.000 claims abstract description 13
- 238000004088 simulation Methods 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims abstract description 5
- 238000005374 membrane filtration Methods 0.000 claims abstract description 3
- 238000000926 separation method Methods 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- 238000001914 filtration Methods 0.000 claims description 16
- 238000010521 absorption reaction Methods 0.000 claims description 14
- 238000003795 desorption Methods 0.000 claims description 14
- 239000012528 membrane Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 239000012530 fluid Substances 0.000 claims description 8
- 238000001471 micro-filtration Methods 0.000 claims description 8
- 238000000605 extraction Methods 0.000 claims description 7
- 230000001954 sterilising effect Effects 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 6
- 238000010828 elution Methods 0.000 claims description 5
- 239000012466 permeate Substances 0.000 claims description 5
- 239000011148 porous material Substances 0.000 claims description 5
- 238000013461 design Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 238000001728 nano-filtration Methods 0.000 claims description 4
- 238000004064 recycling Methods 0.000 claims description 4
- 238000001694 spray drying Methods 0.000 claims description 4
- 239000000919 ceramic Substances 0.000 claims description 3
- 239000004744 fabric Substances 0.000 claims description 3
- 238000001179 sorption measurement Methods 0.000 claims description 3
- 238000005119 centrifugation Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 238000002474 experimental method Methods 0.000 abstract description 4
- 150000004676 glycans Chemical class 0.000 abstract description 3
- 229920001282 polysaccharide Polymers 0.000 abstract description 3
- 239000005017 polysaccharide Substances 0.000 abstract description 3
- 230000001681 protective effect Effects 0.000 abstract description 3
- 235000016068 Berberis vulgaris Nutrition 0.000 abstract description 2
- 241000335053 Beta vulgaris Species 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract description 2
- 229940049413 rifampicin and isoniazid Drugs 0.000 abstract description 2
- 238000007873 sieving Methods 0.000 abstract 1
- 239000007787 solid Substances 0.000 abstract 1
- 238000003809 water extraction Methods 0.000 abstract 1
- 210000004185 liver Anatomy 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 235000013305 food Nutrition 0.000 description 10
- 238000011282 treatment Methods 0.000 description 8
- 206010067125 Liver injury Diseases 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 235000013402 health food Nutrition 0.000 description 5
- 231100000234 hepatic damage Toxicity 0.000 description 5
- 230000008818 liver damage Effects 0.000 description 5
- 230000008439 repair process Effects 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 229960003350 isoniazid Drugs 0.000 description 4
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 4
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 4
- 229960001225 rifampicin Drugs 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000007788 Acute Liver Failure Diseases 0.000 description 2
- 206010000804 Acute hepatic failure Diseases 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 2
- 230000002365 anti-tubercular Effects 0.000 description 2
- 229960003237 betaine Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010008 shearing Methods 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 1
- 206010061623 Adverse drug reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010072268 Drug-induced liver injury Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- 235000002710 Ilex cornuta Nutrition 0.000 description 1
- 241001310146 Ilex cornuta Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 235000017784 Mespilus germanica Nutrition 0.000 description 1
- 244000182216 Mimusops elengi Species 0.000 description 1
- 235000000560 Mimusops elengi Nutrition 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 235000010326 Osmanthus heterophyllus Nutrition 0.000 description 1
- 101710098398 Probable alanine aminotransferase, mitochondrial Proteins 0.000 description 1
- 244000062793 Sorghum vulgare Species 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 235000007837 Vangueria infausta Nutrition 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 231100000836 acute liver failure Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003200 antithyroid agent Substances 0.000 description 1
- 229940043671 antithyroid preparations Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- -1 bicyclic alcohols Chemical class 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000010894 electron beam technology Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000002443 hepatoprotective effect Effects 0.000 description 1
- 231100000334 hepatotoxic Toxicity 0.000 description 1
- 230000003082 hepatotoxic effect Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008798 inflammatory stress Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 235000019713 millet Nutrition 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- SEBFKMXJBCUCAI-DBMPWETRSA-N silybin Chemical compound C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-DBMPWETRSA-N 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000010902 straw Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000003643 water by type Substances 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)
- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
- A61K36/815—Lycium (desert-thorn)
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61K2236/30—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, 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
-
- 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
Abstract
本发明公开了一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,该方法是将枸杞子粉碎、过筛后置于多功能提取罐中,在高速剪切和搅拌低温纯水提取,固液分离后经大孔吸附树脂混合树脂模拟床富集,膜过滤分离纯化,干燥,灭菌而得。经检测,该提取物中,枸杞多糖含量≥65%,甜菜碱含量≥3.0%。活性实验结果表明,本发明制备的枸杞提取物对利福平肝损伤以及异烟肼引起的肝损伤具有较好的保护作用。
Description
技术领域
本发明涉及一种枸杞提取物,尤其涉及一种对药物性肝损伤具有显著的修复和治疗作用的枸杞提取物的制备方法,属于食品、保健食品及药品技术领域。
背景技术
肝脏每分钟要完成500多种功能,以保持身体的正常运转,因此被人们称为“物质代谢中枢”、人体内最大的“化工厂”和“清洁器”,是人体内最大的“解毒工厂”。肝脏是药物代谢的主要场所,大多数药物在体内都要经过肝脏转化或结合作用,由脂溶性变为水溶性,然后从胆汁或尿液排出,某些药物在这个过程中会产生对肝脏有毒性的代谢产物;此外,药物本身及其代谢产物还可以扰乱机体的免疫平衡,最终诱发自身免疫反应。因此,肝脏是最易受到药物影响的器官,容易出现“药物性肝损伤”。药物性肝损伤(DILI)是指由药物或其代谢产物引起的肝脏损害。国际共识意见对药物导致肝脏损害采用统一的术语“肝损伤”,根据用药后肝功能异常情况,将肝损伤定义为血清ALT或总胆红素升高至正常值上限2倍以上;或AST、碱性磷酸酶(ALP)和总胆红素同时升高,且其中至少有1项升高至正常值上限2倍以上。目前我们日常生活中接触的药物及保健品已超过30000种,明确可以引起药物性肝损伤的药物超过1000种,包括抗结核药物、抗肿瘤药物、抗甲状腺药物、抗感染及非甾体抗炎药物、免疫抑制药、麻醉药以及中草药等等。其中临床最常见的是抗结核药物和抗肿瘤药物。因此,药物性肝损伤已成为一个不容忽视的严重公共卫生问题。据世界卫生组织统计,药物性肝损伤已经上升为全球肝病死亡原因的第五位。因为90%的药物需要在肝脏中代谢,所以肝脏成为药物不良反应发生的重要场所。
药物性肝损伤迄今仍缺乏特异的治疗,现代医学在干预肝损伤的治疗方面并无特异性药物,主要治疗原则是及时停用肝毒性药物、支持治疗、监测和防治急性肝衰竭。轻者在停药后或经一般对症处理后可很快好转,重者则需住院治疗。治疗方法包括:停用致病药物,早期清除和排泄体内药物,一般治疗,药物治疗,急性肝功能衰竭的治疗,人工肝支持治疗,肝移植等。
枸杞子有滋补肝肾的功效,为我国传统名贵中药材,也是享誉海内外的滋补食疗珍品,在我国已有2000多年的食用历史,被历版《中国药典》收载。现代科学研究表明,枸杞中的多种因子对损伤的肝细胞有着独特的修复作用,尤其是枸杞糖肽,是枸杞子保护肝脏的主要成分,能够通过缓解细胞炎症和氧化应激损伤发挥作用,对酒精、四氯化碳以及药物诱导的化学性肝损伤均具有显著的保护作用,其保护肝脏的能力和公认的肝脏保护剂水飞蓟素相媲美。因此,从枸杞中提取一种能够有效修复和预防药物性肝损伤的枸杞提取物,将其用于食品、保健食品、特殊医疗用途食品和药品的主要原料,具有十分重要的意义。
发明内容
本发明的目的是提供一种对药物性肝损伤具有修复和治疗作用的枸杞提取物的制备方法,将其应用于食品、保健食品、特殊医疗用途食品和药品,为药物性肝损伤的治疗提供新的途径。
本发明枸杞提取物的制备方法,包括以下工艺步骤:
(1)高速剪切破壁提取:将枸杞子粉碎,过40目筛后,置于多功能提取罐中,加入枸杞子粉体重量10~12倍的纯水,在高速剪切和搅拌下,于60+5℃提取0.5~2 h,得枸杞提取混合液;
所述高速剪切转速为6000~10000rpm,搅拌速度为100~200 rpm。
(2)固液分离:将上述枸杞提取混合液经粗滤,精滤,得枸杞提取液。其中,粗滤可采用三足式离心进行粗滤,滤布孔径为200~400目;也可采用蝶式离心机或卧式离心机进行粗滤,转速均为2000~4000 rpm。精滤可采用管式离心机进行精滤,转速为10000~16000rpm;也可采用陶瓷膜过滤装置进行精滤。
(3)大孔吸附树脂洗脱:将枸杞提取液泵入大孔吸附树脂混合树脂模拟床进行吸附,并收集吸附残液;待上样结束后先用纯水洗脱,再用质量百分数50~60%的乙醇溶液解吸附,回收溶剂至无醇味,得到解吸附液。其中,吸附流速1.0~2.0BV/ h;洗脱流速2~4 BV/ h;解吸附流速3~4 BV/h,温度控制在30~40℃。
大孔吸附树脂混合树脂模拟床包含有2~4根大孔吸附树脂柱,其中至少有2根大孔吸附树脂柱串联;大孔吸附树脂柱的径高比为1:8~1:12。大孔吸附树脂为D101、LX-11、LX-60、LSA-10、LX-28、LX-38、AB-8中至少一种。优选:AB-8与D101以1:0.3~1:3质量比的混合树脂。
(4)膜过滤系统分离:将上述吸附残液先经过微滤膜进行微滤,收集透过液并泵入纳滤膜进行纳滤,收集截留液;所述微滤膜的分子量50000~75000Da,控制压力在2~6 bar、温度在25~40℃;纳滤膜,分子量为3500~5000Da,控制压力为5~10 bar,温度为25~40℃。。
(5)干燥、灭菌:将步骤(3)所得解吸附液和步骤(4)所得截留液充分混合,干燥,灭菌,得到枸杞提取物。
干燥可采用冷冻干燥、喷雾干燥、真空干燥或鼓风干燥,优选喷雾干燥。喷雾干燥的条件为:进风温度:120~180℃,出风温度:80~120℃,料液密度:0.9~1.1。
灭菌方式可采用Co-60辐射灭菌、紫外照射灭菌、电子束灭菌中的至少一种。
本发明制备的枸杞提取物的有效成分为枸杞多糖和甜菜碱,其中,枸杞多糖含量≥65%,甜菜碱含量≥3.0%。具体检查方法按照《中国药典》2015版第一部枸杞子中“枸杞多糖”和“甜菜碱”含量测定方法执行。
以本发明制备的枸杞提取物作为有效成分,和食品、保健食品、特殊医学用途配方食品或药品中可接受的辅料或添加剂进行复配,制备成食品、保健食品或药物制剂。
具体实施方式
下面通过具体实施例对本发明对枸杞子提取物的制备方法、有效成分及对药物性肝损伤具有修复和治疗作用做进一步说明。
实施例1
(1)取优质枸杞子,依次用自来水、纯净水清洗,干燥,粉碎,过40目筛;
(2)取25公斤枸杞子粉,加入多功能提取罐中,再加入250 L纯化水,开启高速剪切机,设定转速为8000rpm;开启搅拌,使其转速为120rpm,待温度升至60℃开始计时,提取0.5 h,得枸杞提取混合液;
(3)将枸杞提取混合液泵入三足式离心机,滤布孔径为200目,离心机转速为3000 rpm,收集离心液200 L;再将离心液泵入管式离心机,转速为16000 rpm,收集离心液,得到枸杞提取液约200 L;
(4)将上述枸杞提取液泵入大孔吸附树脂混合树脂模拟床(径高比1:12,2根树脂柱串联,AB-8:D101为2:1),上样流速为1.5 BV/ h,收集吸附残液;待上样结束后先用2 BV纯水洗脱(洗脱流速为3 BV/ h)后,再用4 BV 60%乙醇溶液解吸附(解吸附流速为3 BV/ h),收集60%乙醇解吸浓缩附液,回收溶剂至无醇味;
(5)将上述吸附残液利用50000 Da的膜系统进行微滤(压力2~4 bar,温度30±5℃),收集透过液;透过液再次泵入分子量为3500Da的纳滤膜系统进行纳滤(压力为6~10 bar,温度为30±5℃);收集截留液并与步骤(4)所得解吸附浓缩液混合;
(6)将上述混合液进行喷雾干燥(进口温度160℃,出口温度100℃),收集干粉,得到枸杞提取物(TCLP)。其各项性能指标见表1。
实施例2
(1)取50公斤优质枸杞子,依次用自来水、纯净水清洗,干燥,粉碎,过40目筛;
(2)将枸杞子粉末加入1T多功能提取罐中,加入10倍量纯水,开启高速剪切机,设定转速为10000 rpm;同时开启搅拌,设定搅拌转速为120 rpm。待温度升至60℃时,开始计时;提取1h,静置2 h,从提取罐侧面的排液口排出枸杞提取液,待温度降至30℃以下卸料,提取工序完成;
(3)枸杞提取液先用蝶式离心机离心(转速为6000 rpm),滤液再用陶瓷膜过滤,收集过滤液;
(4)将上述过滤液泵入大孔吸附树脂树脂模拟床(径高比1:12,2根树脂柱串联,AB-8:D101为1:1),上样流速为2BV/ h,收集吸附残液;待上样结束后先用2 BV纯水洗脱(洗脱流速为3 BV/ h)后,再用4 BV 70%乙醇溶液解吸附(解吸附流速为2 BV/h);收集70%乙醇解吸附液,回收溶剂至无醇味;
(5)将上述经大孔吸附树脂混合模拟床吸附后的吸附残液泵入分子量50000Da的超滤膜系统进行分离(温度30±5℃,压力0~5 bar),透过液继续泵入分子量5000Da的微滤膜系统进行分离(温度30±5℃,压力5~10 bar),收集截留液并与步骤(4)所得解吸附浓缩液混合;
(6)将上述混合液进行喷雾干燥(进口温度160℃,出口温度85℃),收集干粉,得到枸杞提取物(MLBP)。其各项性能指标见表1。
下面通过动物活性试验对上述实施例1、2所得产物TCLP、MLBP对药物性肝损伤具有修复和治疗作用进行说明。
1 实验材料
1.1 试验药物及试剂
TCLP和MLBP为实例1和实例2制备所得样品。临用时用0.5%CMC-Na稀释成所需浓度。双环醇片:25mg/片,18片/盒,批号161107,北京协和药厂,临用时用0.5%CMC-Na
配制成所需浓度。利福平胶囊:150mg/粒,100粒/盒,批号44020771,广东华南药业集团有限公司,临用时用0.5%CMC-Na配制成所需浓度。异烟肼片:100mg/片,100片/粒,批号异烟肼片,广东华南药业集团有限公司,临用时用0.5%CMC-Na配制成所需浓度。试剂盒:谷草转氨酶测定试剂盒,批号2017006;谷丙转氨酶测定试剂盒,批号2017016,试剂盒均由长春汇力生物技术有限公司提供。
1.2实验动物
昆明种小鼠:SPF级,由成都达硕实验动物有限公司提供,许可证号:SCXK(川)2015-030。
1.3主要仪器
JY10001电子秤:良平仪器有限公司生产;JY1003A电子天平:上海精天电子仪器有限公司。全波长多功能酶标仪:VARIOSKAN FLASH,Thermo Scientific,USA.
2实验环境
SPF屏障系统,室内温度20~22℃,相对湿度52%左右,照明12小时明亮,12小时黑暗。合格证号为SYXK(川)20013-100。
3统计学分析
所有数据用均数士标准差(x±s)表示,数量资料采用方差分析,组间差异采用StudentT检验。
4实验方法与结果
4.1 TCLP和MLBP对利福平致大鼠肝损伤模型的影响
将体重为18~22g的雄性小鼠适应性喂养两天后随机分为HGP1200mg/kg组、TCLP50mg/kg组、TCLP100mg/kg组、TCLP300mg/kg纽、MLBP50mg/kg组、MLBP100mg/kg组、MLBP300mg/kg组、模型组、正常对照组、双环醇100mg/kg。药物组给予相应药物,模型组及正常对照组给予等体积0.5%CMC,每天一次,连续7d;在给药第4天,除正常对照组外,其余各组均ip地塞米松100mg/kg,每天一次,连续4次,并在末次注射地塞米松后除正常对照组外各组动物均ig利福平溶液。灌胃后禁食不禁水16h,取血测定血清ALT、AST。处死动物取肝脏称湿重并计算其脏器指数。结果见表1、2:
4.2 TCLP和MLBP对异烟肼致大鼠肝损伤模型的影响
将体重为18~22g的雄性小鼠适应性喂养两天后随机分为HGP1200mg/kg组、TCLP50mg/kg组、TCLP100mg/kg组、TCLP300mg/kg组、MLBP60mg/kg组、MLBP120mg/kg组、MLBP360mg/kg组、模型组、正常对照组。药物组给予相应药物,模型组及正常对照组给予等体积0. 5%CMC,每天2次,连续3次;在末次给药后1小时,除正常对照组外,其余各组均ip异烟肼溶液,在禁食不禁水16h,取血测定血淆ALT,剩余血清冻存(-80℃) 结果详见表3:
研究结果表明,TCLP0.1g/kg及0.3g/kg、MLBP0.065/kg及0.10g/kg均可显著减少利福平肝损伤小鼠的肝脏指数。TCLP、MLBP各剂量组均可显著降低利福平肝损伤小鼠血清谷丙转氨酶活性,HGPl.0g/kg、TCLP0.05g/kg及0.1g/kg、MLBP0.05g/kg及0.10g/kg还可显著减少利福平肝损伤小鼠血清谷草转氨酶活性,与模型组比较具有统计学差异。TCLP0.3g/kg、MLBP 0.05g/kg均可显著降低异烟肼导致肝损伤小鼠血清谷丙转氨酶活性,与模型组比较具有统计学差异。综上所述,TCLP和MLBP均对利福平肝损伤以及异烟肼引起的肝损伤具有较好的保护作用。
Claims (10)
1.一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,包括以下工艺步骤:
(1)高速剪切破壁提取:将枸杞子粉碎,过40目筛后,置于多功能提取罐中,加入枸杞子粉体重量10~12倍的纯水,在高速剪切和搅拌下,于60+5℃提取0.5~2 h,得枸杞提取混合液;
(2)固液分离:将上述枸杞提取混合液经粗滤,精滤,得枸杞提取液;
(3)大孔吸附树脂洗脱:将枸杞提取液泵入大孔吸附树脂混合树脂模拟床进行吸附,并收集吸附残液;待吸附结束后先用纯水洗脱,再用质量百分数50~60%的乙醇溶液解吸附,并回收溶剂至无醇味,得到解吸附液;
(4)膜过滤系统分离:将上述收集的吸附残液先经过微滤膜进行微滤,收集透过液并泵入纳滤膜进行纳滤,收集截留液;
(5)干燥、灭菌:将步骤(3)所得解吸附液和步骤(4)所得截留液充分混合,干燥,灭菌,得到枸杞提取物。
2.如权利要求1所述一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,其特征在于:步骤(1)中,所述高速剪切转速为6000~10000rpm,搅拌速度为100~200rpm。
3.如权利要求1所述一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,其特征在于:步骤(2)中的粗滤采用三足式离心进行粗滤,滤布孔径为200~400目;或采用蝶式离心机、卧式离心机进行粗滤,转速均为2000~4000 rpm。
4.如权利要求1所述一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,其特征在于:步骤(2)中的精滤采用管式离心机进行精滤,转速为10000~16000 rpm;或采用陶瓷膜过滤装置进行精滤。
5.如权利要求1所述一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,其特征在于:步骤(3)中,吸附流速1.0~2.0BV/ h;洗脱流速2~4 BV/ h;解吸附流速3~4BV/h,解吸附温度控制在30~40℃。
6.如权利要求1所述一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,其特征在于:步骤(3)中,大孔吸附树脂混合树脂模拟床包含有2~4根大孔吸附树脂柱,其中至少有2根大孔吸附树脂柱串联;大孔吸附树脂柱的径高比为1:8~1:12。
7.如权利要求6所述一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,其特征在于:大孔吸附树脂为D101、LX-11、LX-60、LSA-10、LX-28、LX-38、AB-8中至少一种。
8.如权利要求7所述一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,其特征在于:大孔吸附树脂为AB-8与D101以1:0.3~1:3质量比的混合树脂。
9.如权利要求1所述一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,其特征在于:步骤(4)中,所述微滤膜的分子量50000~75000Da,控制压力在2~6 bar、温度在25~40℃;纳滤膜的分子量为3500~5000Da,控制压力为5~10 bar,温度为25~40℃。
10.如权利要求1所述一种对药物性肝损伤具有修复和治疗作用枸杞提取物的制备方法,其特征在于:步骤(5)中,干燥采用喷雾干燥,并控制进风温度在120~180℃,出风温度在80~120℃,料液密度在0.9~1.1。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810522804.6A CN108524668B (zh) | 2018-05-28 | 2018-05-28 | 一种对药物性肝损伤具有修复和治疗作用的枸杞提取物的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810522804.6A CN108524668B (zh) | 2018-05-28 | 2018-05-28 | 一种对药物性肝损伤具有修复和治疗作用的枸杞提取物的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN108524668A true CN108524668A (zh) | 2018-09-14 |
CN108524668B CN108524668B (zh) | 2020-12-01 |
Family
ID=63473050
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810522804.6A Active CN108524668B (zh) | 2018-05-28 | 2018-05-28 | 一种对药物性肝损伤具有修复和治疗作用的枸杞提取物的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108524668B (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109490053A (zh) * | 2018-12-12 | 2019-03-19 | 中国科学院兰州化学物理研究所 | 一种植物多糖含量检测的样品前处理方法 |
CN110183511A (zh) * | 2019-06-10 | 2019-08-30 | 中国科学院兰州化学物理研究所 | 一种对抗结核药物诱导的肝损伤具有修复和预防作用的枸杞糖肽制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101991709A (zh) * | 2010-11-09 | 2011-03-30 | 中国科学院西北高原生物研究所 | 抗氧化黑果枸杞提取物制备方法 |
CN104059163A (zh) * | 2014-07-08 | 2014-09-24 | 中国科学院西北高原生物研究所 | 青海柴达木枸杞多糖提取分离制备新方法 |
CN106478836A (zh) * | 2016-11-24 | 2017-03-08 | 中国科学院兰州化学物理研究所 | 一种枸杞多糖的制备方法 |
-
2018
- 2018-05-28 CN CN201810522804.6A patent/CN108524668B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101991709A (zh) * | 2010-11-09 | 2011-03-30 | 中国科学院西北高原生物研究所 | 抗氧化黑果枸杞提取物制备方法 |
CN104059163A (zh) * | 2014-07-08 | 2014-09-24 | 中国科学院西北高原生物研究所 | 青海柴达木枸杞多糖提取分离制备新方法 |
CN106478836A (zh) * | 2016-11-24 | 2017-03-08 | 中国科学院兰州化学物理研究所 | 一种枸杞多糖的制备方法 |
Non-Patent Citations (2)
Title |
---|
周艳华等: "枸杞活性成分提取分离方法研究进展 ", 《食品研究与开发》 * |
张桂: "膜分离技术提取枸杞多糖的工艺 ", 《食品工程》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109490053A (zh) * | 2018-12-12 | 2019-03-19 | 中国科学院兰州化学物理研究所 | 一种植物多糖含量检测的样品前处理方法 |
CN110183511A (zh) * | 2019-06-10 | 2019-08-30 | 中国科学院兰州化学物理研究所 | 一种对抗结核药物诱导的肝损伤具有修复和预防作用的枸杞糖肽制备方法 |
CN110183511B (zh) * | 2019-06-10 | 2023-04-07 | 中国科学院兰州化学物理研究所 | 一种对抗结核药物诱导的肝损伤具有修复和预防作用的枸杞糖肽制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN108524668B (zh) | 2020-12-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5352655B2 (ja) | 草本植物である、ハマウツボ科の全寄生植物[cistanchetubulosa(schenk.)wight]から抽出されるフェニルエタノイド配糖体を含む医薬調製物、これの製造方法およびこれの使用 | |
CN107029120B (zh) | 一种石斛和黄精膏滋剂的制备方法 | |
CN108524668A (zh) | 一种对药物性肝损伤具有修复和治疗作用的枸杞提取物的制备方法 | |
CN110893197A (zh) | 用于治疗痛风的蔓三七提取物及其制备方法 | |
WO2019190161A1 (en) | Whole ginseng composition using ginseng roots, leaves and berries and method of preparing the same | |
CN102091122B (zh) | 一种复方降压中药制剂及其制备方法 | |
CN112675278A (zh) | 润肺止咳、抑制肺部炎症反应的组合物及其制备方法和用途 | |
CN111870627A (zh) | 一种解酒制剂及其制备方法和用途 | |
JP4117029B2 (ja) | ハルパゴフィタム プロカンベンス及び/又はハルパゴフィタム ゼイヘリ デンスから精製された抽出物、その製造方法及びその使用 | |
WO2020012447A1 (en) | Polyherbal formulation and method for production thereof | |
CN107929544B (zh) | 白及属植物中militarine部位及单体的制备方法及其应用 | |
CN115671222A (zh) | 可以改善2型糖尿病的天然复合粉及其制备方法 | |
CN105311337B (zh) | 一种治疗肺部疾病的中药复方组合物及其制备方法 | |
KR20190101063A (ko) | 천연물질 추출물을 함유하는 기관지 질환 예방 및 개선을 위한 조성물 및 그 제조방법 | |
CN104398619A (zh) | 鸡矢藤提取物及其用途 | |
CN105326872A (zh) | 一种对溃疡性结肠炎具有治疗作用的败酱草提取物的制备方法 | |
CN107997170B (zh) | 一种具有降血脂功能的组合物及其制备方法 | |
CN109718268B (zh) | 红豆树种子提取物的制备方法及其在抗炎药物中的应用 | |
CN112007092A (zh) | 一种解酒组合物及其制备方法 | |
CN111743932A (zh) | 一种脱除参类植物提取物中农药残留的工艺 | |
CN101721450B (zh) | 一种用于治疗腹膜炎的苍耳根氯仿提取物的应用 | |
CN105560310B (zh) | 华山矾多糖的药物应用及其组合物 | |
CN109223739A (zh) | 一种组合物及其制备方法和应用 | |
CN112386654B (zh) | 一种中药组合物、提取物及其制备方法与应用 | |
CN105106356B (zh) | 一种脂降宁片的制备方法 |
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 |
Effective date of registration: 20240318 Address after: 748201 Huichuan Industrial Park, Weiyuan County, Dingxi City, Gansu Province Patentee after: Gansu Pharmaceutical Group Longshen Traditional Chinese Medicine Co.,Ltd. Country or region after: China Address before: 730000 No. 18 Tianshui Middle Road, Chengguan District, Gansu, Lanzhou Patentee before: Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences Country or region before: China |
|
TR01 | Transfer of patent right |