CN109568471B - 具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂 - Google Patents
具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂 Download PDFInfo
- Publication number
- CN109568471B CN109568471B CN201910072517.4A CN201910072517A CN109568471B CN 109568471 B CN109568471 B CN 109568471B CN 201910072517 A CN201910072517 A CN 201910072517A CN 109568471 B CN109568471 B CN 109568471B
- Authority
- CN
- China
- Prior art keywords
- parts
- precipitate
- supernatant
- centrifuging
- ethanol
- 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.)
- Active
Links
- 229920000855 Fucoidan Polymers 0.000 title claims abstract description 33
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 241000015177 Saccharina japonica Species 0.000 title claims abstract description 24
- 150000001875 compounds Chemical class 0.000 title claims abstract description 17
- 230000002218 hypoglycaemic effect Effects 0.000 title description 4
- 239000006228 supernatant Substances 0.000 claims abstract description 38
- 239000008280 blood Substances 0.000 claims abstract description 24
- 210000004369 blood Anatomy 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000002156 mixing Methods 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 10
- 230000000694 effects Effects 0.000 claims abstract description 10
- 229940126680 traditional chinese medicines Drugs 0.000 claims abstract description 10
- 238000001816 cooling Methods 0.000 claims abstract description 9
- 238000004108 freeze drying Methods 0.000 claims abstract description 9
- 235000002722 Dioscorea batatas Nutrition 0.000 claims abstract description 6
- 235000006536 Dioscorea esculenta Nutrition 0.000 claims abstract description 6
- 240000001811 Dioscorea oppositifolia Species 0.000 claims abstract description 6
- 235000003416 Dioscorea oppositifolia Nutrition 0.000 claims abstract description 6
- 240000005373 Panax quinquefolius Species 0.000 claims abstract description 6
- 235000003140 Panax quinquefolius Nutrition 0.000 claims abstract description 6
- 244000241838 Lycium barbarum Species 0.000 claims abstract description 5
- 235000015459 Lycium barbarum Nutrition 0.000 claims abstract description 5
- 235000015468 Lycium chinense Nutrition 0.000 claims abstract description 5
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 claims abstract description 5
- 235000006533 astragalus Nutrition 0.000 claims abstract description 5
- 235000013399 edible fruits Nutrition 0.000 claims abstract description 5
- 241000045403 Astragalus propinquus Species 0.000 claims abstract description 4
- 239000008367 deionised water Substances 0.000 claims abstract description 4
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 4
- 239000000047 product Substances 0.000 claims abstract description 4
- 238000002791 soaking Methods 0.000 claims abstract description 4
- 238000005303 weighing Methods 0.000 claims abstract description 4
- 241000304195 Salvia miltiorrhiza Species 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 80
- 239000002244 precipitate Substances 0.000 claims description 45
- 102000004190 Enzymes Human genes 0.000 claims description 18
- 108090000790 Enzymes Proteins 0.000 claims description 18
- 229940088598 enzyme Drugs 0.000 claims description 18
- 239000002994 raw material Substances 0.000 claims description 15
- 108010059892 Cellulase Proteins 0.000 claims description 8
- 108091005804 Peptidases Proteins 0.000 claims description 8
- 108010059820 Polygalacturonase Proteins 0.000 claims description 8
- 239000004365 Protease Substances 0.000 claims description 8
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 8
- 229940106157 cellulase Drugs 0.000 claims description 8
- 108010093305 exopolygalacturonase Proteins 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 241000700159 Rattus Species 0.000 description 20
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 15
- 239000008103 glucose Substances 0.000 description 15
- 241000512259 Ascophyllum nodosum Species 0.000 description 12
- 206010012601 diabetes mellitus Diseases 0.000 description 12
- 241000700157 Rattus norvegicus Species 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000007928 intraperitoneal injection Substances 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 241001466452 Laminariaceae Species 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000003651 drinking water Substances 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 244000132619 red sage Species 0.000 description 3
- 210000005084 renal tissue Anatomy 0.000 description 3
- -1 sulfate compound Chemical class 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- 240000000249 Morus alba Species 0.000 description 2
- 235000008708 Morus alba Nutrition 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000199919 Phaeophyceae Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- 235000014590 basal diet Nutrition 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 235000009200 high fat diet Nutrition 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000005239 tubule Anatomy 0.000 description 2
- 241001061264 Astragalus Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 235000017159 Crataegus pinnatifida Nutrition 0.000 description 1
- 241000657480 Crataegus pinnatifida Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- 241000199900 Laminariales Species 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
- 206010028980 Neoplasm Diseases 0.000 description 1
- 244000046146 Pueraria lobata Species 0.000 description 1
- 235000010575 Pueraria lobata Nutrition 0.000 description 1
- 241000405414 Rehmannia Species 0.000 description 1
- 241001017629 Saccharina sculpera Species 0.000 description 1
- 240000007164 Salvia officinalis Species 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
- 235000007837 Vangueria infausta Nutrition 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 229940107666 astragalus root Drugs 0.000 description 1
- 210000002665 bowman capsule Anatomy 0.000 description 1
- 210000001736 capillary Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 210000005086 glomerual capillary Anatomy 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 210000003878 glomerular mesangial cell Anatomy 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000003584 mesangial cell Anatomy 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 235000005412 red sage Nutrition 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 231100001028 renal lesion Toxicity 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 210000004233 talus Anatomy 0.000 description 1
- 210000004926 tubular epithelial cell 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
Images
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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/894—Dioscoreaceae (Yam family)
- A61K36/8945—Dioscorea, e.g. yam, Chinese yam or water yam
-
- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
-
- 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)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/488—Pueraria (kudzu)
-
- 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)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
-
- 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)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
- A61K36/605—Morus (mulberry)
-
- 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)
- A61K36/80—Scrophulariaceae (Figwort family)
- A61K36/804—Rehmannia
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
-
- 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
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Polymers & Plastics (AREA)
- Urology & Nephrology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明公开一种具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂,由笼目海带海带岩藻聚糖硫酸酯和中药复合制剂按照质量比为1:1混合而成;所述中药复合制剂依次按照如下步骤制备:称取通过60目的中药,所述中药组分及质量比为黄芪23、生地黄20、葛根10、丹参20、山药10、枸杞子8、桑叶5及西洋参4,加8倍体积去离子水,冷水浸泡60 min;分两次煎熬提取,合并提取液;将提取液冷却至60℃,3500 r/min离心10 min后取上清液;将上清液低温冷冻干燥,收集制品。各组分相互配合,可有效降低血糖,无毒副作用,适用于糖尿病患者。
Description
技术领域
本发明涉及一种降血糖药物,尤其是一种具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂。
背景技术
褐藻聚糖硫酸酯(fucoidan)是一种水溶性结合有硫酸基团的活性杂多糖,主要成分为岩藻糖和硫酸基。褐藻聚糖硫酸酯具有广泛的生理和生物活性,研究表明,不同的提取方法、不同的藻类中提取的褐藻聚糖硫酸酯,其组成成分和结构等存在较大差异。褐藻聚糖硫酸酯的生物活性不但取决于其组成成分、结构、硫酸基团的含量及其位置,还取决于可能与多糖链接的多酚含量。笼目海带(Kjellmaniella crassifolia Miyabe)为褐藻优势种质资源,它在系统分类上属于海带目(Laminariales),海带科(Laminariaceae),Kjellmaniella属,是近几年研究团队培育栽培的优质褐藻。笼目海带一方面富含褐藻聚糖硫酸酯,另一方面因低温的生长环境使其富含以U-fucoidan为主的优质褐藻聚糖硫酸酯,具有抗肿瘤、降血脂、保肝护肝等多种生物活性。
黄芪、生地黄、葛根、丹参、山药、枸杞子、桑叶及西洋参均为常用的中药,分别有提高免疫力、调节脾胃等功效,但迄今为止并没有与笼目海带褐藻聚糖硫酸酯进行合理复配制备降血糖药物的相关报道。
发明内容
本发明是为了解决现有技术所存在的上述技术问题,提供一种具有降血糖作用的褐藻聚糖硫酸酯复方制剂。
本发明的技术解决方案是:一种具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂,其特征在于由笼目海带海带岩藻聚糖硫酸酯和中药复合制剂按照质量比为1:1混合而成;
所述笼目海带褐藻聚糖硫酸酯依次按照如下步骤制备:以清洗后的笼目海带为原料,向原料中加入复合酶,在 pH4.0~pH5.5和温度40~60℃条件下酶解40~70分钟,所述复合酶添加量为原料质量的0.51~0.90%,然后在96~100℃水浴加热3~4小时,降至室温,离心得上清液A,所述复合酶由纤维素酶、果胶酶和蛋白酶按质量比为5:5~8:0.1~0.5混合而成;在上清液A中加入乙醇至乙醇质量浓度为20%产生沉淀,离心得上清液B;在上清液B中加入乙醇至乙醇质量浓度为60%产生沉淀,离心得沉淀;将沉淀溶于水中,加入乙醇至乙醇质量浓度为30%产生沉淀,离心去沉淀得上清液C;在上清液C中继续添加乙醇至乙醇质量浓度为70%产生沉淀,离心得沉淀;冷冻干燥沉淀得白色粉末;
所述中药复合制剂依次按照如下步骤制备:称取通过60目的中药,所述中药组分及质量比为黄芪23、生地黄20、葛根10、丹参20、山药10、枸杞子8、桑叶5及西洋参4,加8倍体积去离子水,冷水浸泡60 min;分两次煎熬提取,合并提取液;将提取液冷却至60 ℃,3500r/min离心10 min后取上清液;将上清液低温冷冻干燥,收集制品。
本发明笼目海带褐藻聚糖硫酸酯与黄芪、生地黄、葛根、丹参、山药、枸杞子、桑叶及西洋参等中药有效成分进行合理复配,各组分相互配合,可有效降低血糖,无毒副作用,适用于糖尿病患者。
附图说明
图1是各实验组糖尿病大鼠肾脏组织HE染色形态学观察(400×)图。
具体实施方式
实施例1:
本发明的具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂(KCA),由笼目海带海带岩藻聚糖硫酸酯和中药复合制剂按照质量比为1:1混合而成;
所述笼目海带褐藻聚糖硫酸酯(KF)依次按照如下步骤制备:以清洗后的笼目海带为原料,向原料中加入复合酶,在 pH5.5和温度60℃条件下酶解40分钟,所述复合酶添加量为原料质量的0.90%,然后在100℃水浴加热3小时,降至室温,离心得上清液A,所述复合酶是取5.0g纤维素酶,5.0g果胶酶和0.1g蛋白酶混合配制而成,纤维素酶、果胶酶和蛋白酶的酶活分别为80,000u/g、80,000 u/g和1,000,000 u/g;在上清液A中加入乙醇至乙醇质量浓度为20%产生沉淀,离心得上清液B;在上清液B中加入乙醇至乙醇质量浓度为60%产生沉淀,离心得沉淀;将沉淀溶于水中,加入乙醇至乙醇质量浓度为30%产生沉淀,离心去沉淀得上清液C;在上清液C中继续添加乙醇至乙醇质量浓度为70%产生沉淀,离心得沉淀;冷冻干燥沉淀得白色粉末;
所述中药复合制剂(ACM)依次按照如下步骤制备:称取通过60目的中药,所述中药组分及质量比为黄芪23g、生地黄20g、葛根10g、丹参20g、山药10g、枸杞子8g、桑叶5g及西洋参4g,加8倍体积去离子水,冷水浸泡60 min;分两次煎熬提取,首次熬制45 min,末次熬制35 min,合并提取液;将提取液冷却至60 ℃,3500 r/min离心10 min后获得上清液;将上清液低温冷冻干燥,收集制品。
实施例2:
与实施例1所不同的是笼目海带褐藻聚糖硫酸酯(KF)依次按照如下步骤制备:以清洗后的笼目海带为原料,向原料中加入复合酶,在 pH4.0和温度40℃条件下酶解70分钟,所述复合酶添加量为原料质量的0.51%,然后在96℃水浴加热4小时,降至室温,离心得上清液A,所述复合酶是取5.0g纤维素酶,8.0g果胶酶和0.5g蛋白酶混合配制而成,纤维素酶、果胶酶和蛋白酶的酶活分别为80,000u/g、80,000 u/g和1,000,000 u/g;在上清液A中加入乙醇至乙醇质量浓度为20%产生沉淀,离心得上清液B;在上清液B中加入乙醇至乙醇质量浓度为60%产生沉淀,离心得沉淀;将沉淀溶于水中,加入乙醇至乙醇质量浓度为30%产生沉淀,离心去沉淀得上清液C;在上清液C中继续添加乙醇至乙醇质量浓度为70%产生沉淀,离心得沉淀;冷冻干燥沉淀得白色粉末。
实施例3:
与实施例1所不同的是笼目海带褐藻聚糖硫酸酯(KF)依次按照如下步骤制备:以清洗后的笼目海带为原料,向原料中加入复合酶,在 pH5.0和温度50℃条件下酶解50分钟,所述复合酶添加量为原料质量的0.80%,然后在98℃水浴加热3.5小时,降至室温,离心得上清液A,所述复合酶是取5.0g纤维素酶,6.5g果胶酶和0.3g蛋白酶混合配制而成,纤维素酶、果胶酶和蛋白酶的酶活分别为80,000u/g、80,000 u/g和1,000,000 u/g;在上清液A中加入乙醇至乙醇质量浓度为20%产生沉淀,离心得上清液B;在上清液B中加入乙醇至乙醇质量浓度为60%产生沉淀,离心得沉淀;将沉淀溶于水中,加入乙醇至乙醇质量浓度为30%产生沉淀,离心去沉淀得上清液C;在上清液C中继续添加乙醇至乙醇质量浓度为70%产生沉淀,离心得沉淀;冷冻干燥沉淀得白色粉末。
对实施例1、实施例2、实施例3所得笼目海带褐藻聚糖硫酸酯、中药制剂进行分析,笼目海带褐藻聚糖硫酸酯的纯度为80.0%以上,总糖质量为50.0~65.0%,硫酸根质量21.0~35.0%%,中药制剂的总糖含量为90.0%以上,黄酮含量为6.0%以上,蛋白质含量为4%以上。
实验:
1. 动物实验说明
Ⅱ型糖尿病大鼠模型建立。SPF级Wistar雄性大鼠96只,实验分组如表1所示,给予基础饲料适应性喂养一周后,预留Wistar大鼠12只,作为空白对照组,15周实验期间给予基础饲料,其余各组大鼠依次给予高糖高脂饲料(1-13周)和高脂饲料(13-15周)。实验第五周,空白对照组大鼠腹腔注射无菌生理盐水(10 mL·kg-1 BW.ip);其余Wistar大鼠腹腔注射30 mg·kg-1 BW.ip STZ(实验前预冷后枸橼酸盐缓冲液配制);腹腔注射4 h后,各实验大鼠饮水更换为5 %葡萄糖(24 h),避免注射STZ后低血糖导致小鼠死亡。首次腹腔注射7 d后,再次腹腔注射。空白对照组Wistar大鼠,腹腔注射无菌生理盐水(10 mL·kg-1 BW.ip);剩余Wistar大鼠,腹腔再次注射30 mg·kg-1 BW.ip STZ;腹腔注射4 h后,各实验大鼠饮水更换为5 %葡萄糖(24 h)。糖尿病大鼠稳定性观察7 d后,动物禁食10 h,尾尖针刺取血,测定空腹血糖值,注射STZ组小鼠血糖值>11 mmol/L为高血糖建模成功动物。建模成功后,实验动物组按血糖值随机分组,实验周期共计15周。实验期间,均给予正常饮水。
表1 实验动物分组及给药
表1中KCA为本发明实施例3制备的笼目海带褐藻聚糖硫酸酯复方制剂。
2. 本发明实施例3笼目海带褐藻聚糖硫酸酯复方制剂对Ⅱ型糖尿病降空腹血糖值的降低作用
造模成功后各组糖尿病大鼠空腹血糖值如表2所示。
表2笼目海带褐藻聚糖硫酸酯复方制剂对糖尿病大鼠空腹血糖值影响
结果表明造模成功后各组糖尿病大鼠空腹血糖值显著高于空白对照组(Control),各药物干预组空腹血糖值与模型组(Negative)组间无显著性差异;模型组(Negative)组糖尿病大鼠空腹血糖值在造模成功后无明显差异,这表明糖尿病大鼠造模成功且在灌胃期间保存稳定。灌胃2周后,KCB各组的大鼠组空腹血糖值相较模型组(Negative)无显著差异;灌胃至第八周,大鼠空腹血糖值测定结果显示Positive组、KCB-L组、KCB-M组、KCB-H组糖尿病大鼠空腹血糖值显著或极显著下降。阳性对照组(Positive)大鼠空腹血糖值较模型组(Negative)下降26.65 %,KCB-L组、KCB-M组、KCB-H组大鼠空腹血糖值下降38.65 %、25.18 %、37.84 %,由此可见,本发明的笼目海带褐藻聚糖硫酸酯复方制剂对Ⅱ型糖尿病治疗效果优于中药制剂和褐藻聚糖硫酸酯。
3.各实验组糖尿病大鼠肾脏组织HE染色形态学观察(400×)
肾脏组织光镜观察结果如图1所示,图中a:Control组;b:Negative组;c:Positive组;d:KF组;e:CHM组;f:KCB-L组;g:KCB-M组;h:KCB-H组。结果表明:空白对照组(Control)Wistar大鼠肾小球和肾小管结构完整、紧密,为表现出病理学变化。而模型组(Negative)糖尿病大鼠肾小球面积增大,系膜增宽、系膜细胞增生,细胞外基质增多;肾小管上皮细胞出现空泡样变,管腔扩张,肾间质被炎症细胞浸润;同时肾小球内及肾小管周围可见大量胶原质纤维沉积,且肾小球包曼氏囊扩张明显,系膜基质增宽,肾小球毛细血管基底膜增厚。比较模型组(Negative)组,阳性对照组(Positive)糖尿病大鼠肾小球系膜细胞增生水平及肾间质炎症细胞浸润降低,肾脏纤维化水平和系膜基质厚度也得到改善,肾小球毛细血管基底膜轻度增厚,其它干预组糖尿病大鼠肾脏病变均有不同程度的减轻,特别是KCB剂量组(低、中、高剂量组)糖尿病肾病抑制效果最佳。
Claims (1)
1. 一种具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂,其特征在于由笼目海带海带岩藻聚糖硫酸酯和中药复合制剂按照质量比为1:1混合而成,灌胃剂量为100 mg·kg-1·day-1;
所述笼目海带海带岩藻聚糖硫酸酯依次按照如下步骤制备:以清洗后的笼目海带为原料,向原料中加入复合酶,在 pH4.0~pH5.5和温度40~60℃条件下酶解40~70分钟,所述复合酶添加量为原料质量的0.51~0.90%,然后在96~100℃水浴加热3~4小时,降至室温,离心得上清液A,所述复合酶由纤维素酶、果胶酶和蛋白酶按质量比为5:5~8:0.1~0.5混合而成;在上清液A中加入乙醇至乙醇质量浓度为20%产生沉淀,离心得上清液B;在上清液B中加入乙醇至乙醇质量浓度为60%产生沉淀,离心得沉淀;将沉淀溶于水中,加入乙醇至乙醇质量浓度为30%产生沉淀,离心去沉淀得上清液C;在上清液C中继续添加乙醇至乙醇质量浓度为70%产生沉淀,离心得沉淀;冷冻干燥沉淀得白色粉末;
所述中药复合制剂依次按照如下步骤制备:称取通过60目的中药,所述中药组分及质量比为黄芪23、生地黄20、葛根10、丹参20、山药10、枸杞子8、桑叶5及西洋参4,加8倍体积去离子水,冷水浸泡60 min;分两次煎熬提取,合并提取液;将提取液冷却至60 ℃,3500 r/min离心10 min后取上清液;将上清液低温冷冻干燥,收集制品。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910072517.4A CN109568471B (zh) | 2019-01-25 | 2019-01-25 | 具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910072517.4A CN109568471B (zh) | 2019-01-25 | 2019-01-25 | 具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109568471A CN109568471A (zh) | 2019-04-05 |
CN109568471B true CN109568471B (zh) | 2021-12-21 |
Family
ID=65917445
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910072517.4A Active CN109568471B (zh) | 2019-01-25 | 2019-01-25 | 具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109568471B (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007118368A1 (fr) * | 2006-04-18 | 2007-10-25 | Fasheng Wang | Thé pharmaceutique destiné à réduire la glycémie et procédé associé |
CN108610433A (zh) * | 2018-04-10 | 2018-10-02 | 山东海之宝海洋科技有限公司 | 可有效抑制肝肿瘤细胞Hca-F的笼目海带提取物及制备方法 |
-
2019
- 2019-01-25 CN CN201910072517.4A patent/CN109568471B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007118368A1 (fr) * | 2006-04-18 | 2007-10-25 | Fasheng Wang | Thé pharmaceutique destiné à réduire la glycémie et procédé associé |
CN108610433A (zh) * | 2018-04-10 | 2018-10-02 | 山东海之宝海洋科技有限公司 | 可有效抑制肝肿瘤细胞Hca-F的笼目海带提取物及制备方法 |
Non-Patent Citations (2)
Title |
---|
参藤三黄汤治疗2型糖尿病;周小琳;《中国实验方剂学杂志》;20130520;第19卷(第10期);第298-301页 * |
萱藻中褐藻多糖硫酸酯的纯化及其组分分析;周晓等;《大连海洋大学学报》;20180425;第33卷(第02期);第239-243页 * |
Also Published As
Publication number | Publication date |
---|---|
CN109568471A (zh) | 2019-04-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102824545B (zh) | 一种降糖中药组合物 | |
CN103070880B (zh) | 白簕多糖在制备治疗糖尿病药物中的应用 | |
CN110604794A (zh) | 一种降尿酸降血糖的中药制剂和功能饮料制备方法 | |
CN109568471B (zh) | 具有降血糖作用的笼目海带褐藻聚糖硫酸酯复方制剂 | |
CN109232757B (zh) | 核桃叶多糖提取物及应用 | |
CN111138557A (zh) | 一种栀子多糖及其制备方法和应用 | |
CN103446278A (zh) | 一种海棠提取物及其制备、应用 | |
CN102614457B (zh) | 一种乳康片的制备方法 | |
CN105145931A (zh) | 一种降糖茶及其加工方法 | |
CN102028834B (zh) | 一种复方龙血竭制剂及其制备方法 | |
Mohd et al. | Antidiabetic activity of the aqueous extract of Annona squamosa in Streptozotocin inducedhyperglycemic rats | |
CN1329066C (zh) | 一种生脉注射制剂及其制备方法 | |
CN104546988B (zh) | 一种瓜蒌多糖免疫增强剂的制备方法 | |
CN103566227B (zh) | 一种防治2型糖尿病的中药组合物及其制备方法 | |
CN108853184B (zh) | 一种青钱柳和多穗柯提取物组合 | |
CN107684601B (zh) | 一种能够降血糖的复方颗粒及其制备方法 | |
CN100355415C (zh) | 黄芪冻干粉针剂的制备方法 | |
CN106822228B (zh) | 一种山豆根多糖有效部位及其制备方法 | |
CN103800736A (zh) | 一种治疗高血压肾病的药物组合物及其应用 | |
CN108295032A (zh) | 采用抗性糊精制备中药配方颗粒的方法 | |
CN108685964A (zh) | 毛大丁草提取物的应用及其有效组分制备方法 | |
CN103751255A (zh) | 一种具有降血糖功能的茯苓多糖组合物及其制备方法 | |
CN102247352A (zh) | 槲皮素-7-硫酸酯钠盐的制备方法及其在制备抗血栓药物和保健品中的应用 | |
CN1785251B (zh) | 一种含丹参的药物粉针剂 | |
CN101040982A (zh) | 一种中药降糖组合物 |
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 |