CN103977019B - 五味子总多糖在制备用于治疗咳嗽的药物或保健品中的应用 - Google Patents
五味子总多糖在制备用于治疗咳嗽的药物或保健品中的应用 Download PDFInfo
- Publication number
- CN103977019B CN103977019B CN201410209951.XA CN201410209951A CN103977019B CN 103977019 B CN103977019 B CN 103977019B CN 201410209951 A CN201410209951 A CN 201410209951A CN 103977019 B CN103977019 B CN 103977019B
- Authority
- CN
- China
- Prior art keywords
- cough
- fruit
- chinese magnoliavine
- total starches
- medicine
- 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
- 206010011224 Cough Diseases 0.000 title claims abstract description 160
- 240000006079 Schisandra chinensis Species 0.000 title claims abstract description 88
- 235000013399 edible fruits Nutrition 0.000 title claims abstract description 75
- 229920002472 Starch Polymers 0.000 title claims abstract description 71
- 235000019698 starch Nutrition 0.000 title claims abstract description 71
- 239000003814 drug Substances 0.000 title claims abstract description 37
- 230000036541 health Effects 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 208000037883 airway inflammation Diseases 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- 208000013116 chronic cough Diseases 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000000284 extract Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 13
- 239000006188 syrup Substances 0.000 claims description 13
- 235000020357 syrup Nutrition 0.000 claims description 13
- 239000000047 product Substances 0.000 claims description 12
- 235000008422 Schisandra chinensis Nutrition 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000012360 testing method Methods 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 235000008504 concentrate Nutrition 0.000 claims description 6
- 239000012141 concentrate Substances 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 239000002244 precipitate Substances 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 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 claims description 5
- -1 filter Substances 0.000 claims description 5
- 238000005238 degreasing Methods 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 239000003208 petroleum Substances 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 238000010298 pulverizing process Methods 0.000 claims description 3
- 239000007901 soft capsule Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 229940098465 tincture Drugs 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000007887 hard shell capsule Substances 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 abstract description 63
- 239000000779 smoke Substances 0.000 abstract description 22
- 235000019504 cigarettes Nutrition 0.000 abstract description 20
- 230000035945 sensitivity Effects 0.000 abstract description 19
- 230000011514 reflex Effects 0.000 abstract description 18
- 230000000638 stimulation Effects 0.000 abstract description 8
- 238000002474 experimental method Methods 0.000 abstract description 5
- 230000008030 elimination Effects 0.000 abstract description 2
- 238000003379 elimination reaction Methods 0.000 abstract description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 17
- 210000004072 lung Anatomy 0.000 description 16
- 230000000694 effects Effects 0.000 description 14
- 229940079593 drug Drugs 0.000 description 13
- 241000700199 Cavia porcellus Species 0.000 description 11
- 238000000889 atomisation Methods 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 239000000243 solution Substances 0.000 description 7
- 208000011580 syndromic disease Diseases 0.000 description 7
- 210000003734 kidney Anatomy 0.000 description 6
- 230000000954 anitussive effect Effects 0.000 description 5
- 229940124584 antitussives Drugs 0.000 description 5
- 229960004126 codeine Drugs 0.000 description 5
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 5
- 150000004676 glycans Chemical class 0.000 description 5
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 5
- 210000004969 inflammatory cell Anatomy 0.000 description 5
- 230000007170 pathology Effects 0.000 description 5
- 229920001282 polysaccharide Polymers 0.000 description 5
- 239000005017 polysaccharide Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 235000019640 taste Nutrition 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 230000003203 everyday effect Effects 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000003958 fumigation Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000003595 mist Substances 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 210000004493 neutrocyte Anatomy 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 241000700198 Cavia Species 0.000 description 3
- 206010062717 Increased upper airway secretion Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 208000026435 phlegm Diseases 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000000391 smoking effect Effects 0.000 description 3
- 231100000167 toxic agent Toxicity 0.000 description 3
- 239000003440 toxic substance Substances 0.000 description 3
- 239000011800 void material Substances 0.000 description 3
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- 206010065563 Eosinophilic bronchitis Diseases 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 241001627955 Tetraodon lineatus Species 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 208000017574 dry cough Diseases 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 239000003517 fume Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 2
- 230000005180 public health Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 1
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- KJDJOFDHMKYIBP-UHFFFAOYSA-N C=CCCCCCC.C1(CCCCC1)C1=C(C=CC=C1)C1=CC=CC=C1 Chemical compound C=CCCCCCC.C1(CCCCC1)C1=C(C=CC=C1)C1=CC=CC=C1 KJDJOFDHMKYIBP-UHFFFAOYSA-N 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010073508 Drug reaction with eosinophilia and systemic symptoms Diseases 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241001506371 Kadsura Species 0.000 description 1
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 244000181025 Rosa gallica Species 0.000 description 1
- 235000000533 Rosa gallica Nutrition 0.000 description 1
- 241000736078 Schisandra sphenanthera Species 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 241000256856 Vespidae Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000002929 anti-fatigue Effects 0.000 description 1
- 230000001147 anti-toxic effect Effects 0.000 description 1
- 230000000259 anti-tumor 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
- 208000006673 asthma Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000003546 flue gas Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000011554 guinea pig model Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 230000008518 non respiratory effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-N sodium;5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)NC1=O QGMRQYFBGABWDR-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Classifications
-
- 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
-
- 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
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
-
- 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
- A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P10/00—Shaping or working of foodstuffs characterised by the products
-
- 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)
- A61K36/79—Schisandraceae (Schisandra family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- 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
- A61K2236/15—Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Food Science & Technology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Molecular Biology (AREA)
- Nutrition Science (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及五味子总多糖在制备治疗咳嗽的药物或保健品中的新用途,具体如在制备治疗镇咳、缓解咳嗽及消除气道炎症的药物或保健品中的新用途。实验表明五味子总多糖能显著减少香烟烟雾刺激致咳嗽敏感性增高豚鼠及柠檬酸烟雾刺激致急性咳嗽豚鼠的咳嗽次数,延长咳嗽潜伏期,并能显著减轻香烟烟雾刺激致咳嗽敏感性增高豚鼠的气道炎症,提示五味子总多糖可用于制备镇咳、缓解咳嗽及消除气道炎症的药物。
Description
技术领域
本发明属于生物医药领域,涉及五味子总多糖在制备用于治疗咳嗽的药物或保健品的用途,特别是五味子总多糖在制备镇咳、缓解咳嗽及消除气道炎症的药物或保健品中的新用途。
背景技术
咳嗽是内科门诊最常见的症状,见于多种呼吸系统及非呼吸系统疾病。咳嗽本身是一种防御机制,清除气道内过多的分泌物及防止异物误吸入气道。但持续长时间的咳嗽却严重影响了患者的生活质量并造成患者严重的心理负担,同时也显著增加了个人及公共医疗卫生支出。
按照病程来分,咳嗽包括急性咳嗽(<3周)、亚急性咳嗽(3~8周)和慢性咳嗽(≥8周)。目前咳嗽的治疗一般都是采用中枢性镇咳药、周围性镇咳药及祛痰药等进行治疗,一般都能收到较好的疗效。但仍有部分急慢性咳嗽即使采用可待因等中枢性镇咳药物,咳嗽仍旧不能得到缓解,以致许多急性咳嗽发展成为慢性咳嗽,有的慢性咳嗽患者病程甚至达到几十年。
多份国外流行病学研究显示慢性咳嗽在普通人群的发病率约9%~33%,2003年一项英国流行病学调查显示,慢性咳嗽在50~59岁的中年人发病率达12%,慢性咳嗽患者约占呼吸专科门诊患者的20%。近年随着大气环境污染的逐渐加重(如PM2.5、PM10等),慢性咳嗽的患病率还可能继续上升。目前的研究认为导致慢性咳嗽的主要病因包括:咳嗽变异性哮喘、嗜酸粒细胞性支气管炎、胃食管反流性咳嗽、上气道咳嗽综合征。对于上述病因引起的咳嗽,遵循咳嗽指南进行相应的治疗,大部分患者咳嗽可得到明显缓解。然而,仍有部分慢性咳嗽患者经过系列全面的检查后,未见明显异常,但咳嗽症状持续存在,既往称之为慢性特发性咳嗽(Chronic idiopathic cough,CIC),其咳嗽症状治疗不佳,且无针对性病因治疗,是目前慢性咳嗽领域的难点及重点所在。有研究发现慢性特发性咳嗽以中年人多见,多以感冒为触发因素,此后咳嗽长期存在,通常对油烟、刺激性气味、冷空气、香烟烟雾等异常敏感,有时甚至大笑或讲话可诱发咳嗽,表现为咳嗽敏感性明显增高。针对此种情况,将咳嗽敏感性增高的慢性咳嗽称之为咳嗽高敏综合征(Cough hypersensitivitysyndrome,CHS)。咳嗽敏感性异常增高是慢性咳嗽高敏综合征患者共有的关键特征。
目前对于咳嗽高敏综合征的患者,暂无合适的治疗手段可供选择,大多靠镇咳药物维持治疗。但镇咳药物,如可待因及右美沙芬等,存在着不同程度的副作用,如便秘、镇静、呼吸抑制等,因而限制了其使用,而且部分咳嗽高敏综合征的患者甚至使用中枢性镇咳药物,咳嗽亦不能缓解,严重影响日常生活质量。
五味子味酸、甘,性温。归肺、心、肾经。肺为娇脏,恶燥,五味子甘温而润,润肺止咳;久咳致肾不纳气,五味子味酸收敛,助肾纳气,治疗肺阴亏虚、肾不纳气所致久咳可谓功效极大。《本草会编》记载:“劳嗽,宜用北者;风寒在肺,宜用南者”;《药品化义》记载:“五味子……能收敛肺气,主治虚劳久咳”;《本草求原》记载:“五味子,为咳嗽要药,凡风寒咳嗽、伤暑咳嗽、伤燥咳嗽、劳伤咳嗽、肾水虚咳、肾火虚咳、久咳喘促……皆用之”。张仲景明确指出:凡咳者均可加入五味子。《中华人民共和国药典》载其用于“久咳虚喘,……心悸失眠”。中医临床上五味子广泛用于咳嗽后期的干咳无痰或久咳不已的肺虚咳嗽病症。
五味子的化学成分主要为挥发油类、木脂素类、三萜类、有机酸类及多糖类,其中联苯环辛烯木脂素类和降三萜内酯类成分是五味子属植物的特征性成分。五味子药理活性广泛,相关报道众多,尤其是其对肝脏的保护作用及宁心安神作用方面,研究较多。
多糖类成分是五味子药材中的一类重要成分,含量在10%左右,据报道,五味子总多糖具有保肝、提高免疫力、抗衰老、抗疲劳、抗肿瘤、降脂减肥、抗氧化等功效。但是,五味子总多糖作为五味子药材中含量极大的一类成分,一直未见关于其对咳嗽是否有缓解功效的文献报道。
发明内容
本发明的目的在于提供五味子总多糖的新用途,具体在于提供五味子总多糖在制备治疗咳嗽的药物或保健品中的新用途。
进一步的,本发明提供五味子总多糖在制备用于治疗急性、亚急性或慢性咳嗽的药物或保健品中的新用途。
进一步的,本发明还提供五味子总多糖在制备用于镇咳、缓解咳嗽或消除气道炎症的药物或保健品中的应用。
所述五味子总多糖,是从五味子药材中提取得到的,用苯酚-硫酸法检测,其多糖类成分含量以D-葡萄糖计,为50%~100%(质量)。
所述的五味子可以是五味子Schisandra chinensis(Turcz.)Baill.(即北五味子)和/或华中五味子Schisandra sphenanthera Rehd.et Wils.(即南五味子)。
所述五味子总多糖可制成药学上可接受的剂型,所述剂型例如但不限于片剂、硬胶囊、软胶囊、散剂、酊剂、口服液、糖浆、颗粒剂、丸剂或注射剂。本领域技术人员可以采用本技术领域的常规制剂工艺将五味子总多糖制成所需的剂型。例如,可采用现有工艺将五味子总多糖制成颗粒剂:取五味子总多糖,与辅料淀粉、蔗糖以及崩解剂混合后,加入用水溶解的粘合剂纤维素衍生物溶液进行混合,采用挤出制粒法将药物制成软粒,干燥,过筛,筛上物适当粉碎后再过筛,直至制成均匀颗粒,将制得的颗粒进行分装,每袋10g。
本发明的五味子总多糖采用本技术领域现有的常规方法从五味子药材中提取得到,具体可以通过石油醚脱脂、水煎煮、乙醇沉淀、脱蛋白、脱色等步骤制成。
本发明针对咳嗽的临床治疗现状及难点,采用香烟烟雾刺激致咳嗽敏感性增高豚鼠模型及柠檬酸烟雾刺激致急性咳嗽豚鼠模型进行了实验,结果表明,五味子总多糖能显著延长香烟烟雾刺激致咳嗽敏感性增高豚鼠及柠檬酸烟雾刺激致急性咳嗽豚鼠的咳嗽潜伏期、减少咳嗽次数,显著减少香烟烟雾刺激致咳嗽敏感性增高豚鼠肺泡灌洗液中炎症细胞总数及中性粒细胞比例,病理切片观察提示五味子总多糖干预后豚鼠细支气管周炎症细胞浸润明显减少,管腔内渗出减轻,肺泡间隔增宽程度减轻,提示五味子总多糖对豚鼠的气道炎症具有显著的抑制作用。并且五味子总多糖的作用明显好于五味子水提取物,且呈一定量效关系,表现出镇咳、缓解咳嗽及消除气道炎症方面的应用前景。对于临床上咳嗽高敏患者,五味子总多糖具有制备成用于治疗这些患者的有效药物的应用前景。
附图说明
图1,为实施例一豚鼠肺组织和气道病理切片代表图(HE×200),
图2,为五味子总多糖不同时间点对柠檬酸烟雾刺激豚鼠咳嗽次数的影响。
具体实施方式
下面结合实施例及附图对本发明作进一步详细的描述,但本发明并不限于此。
具体实施例中所用的实验动物:纯白Hartly豚鼠,普通级,雄性,体重300±50g,广东省实验动物中心提供(SCXK(粤)2008-0002)。豚鼠饲养在相对清洁、安静、恒温(23±3℃)、恒湿(55±15%)环境中,日夜周期为12:12小时/天,分笼饲养,5只/笼,可自由获得食物和水。
具体实施例中所用的药物、试剂、及仪器:
1)五味子总多糖,其制备过程为:
将五味子药材粉碎,粉碎后用石油醚脱脂,然后用8倍量水煎煮3次,所得煎煮液进行浓缩,浓缩液用80%乙醇沉淀、过滤、沉淀酶法脱蛋白、活性炭脱色,用80%乙醇反复洗涤后进行干燥,得五味子总多糖,经检测,以D-葡萄糖计,其多糖含量为89%;
2)五味子水提取物,其制备过程为:
五味子药材粉碎→8倍量水煎煮2h,共煎煮3次→煎煮液浓缩,干燥→五味子水提取物;
3)0.9%氯化钠注射液:东莞普济药业有限公司。戊巴比妥钠:美国Merck公司。可待因:国药集团工业股份有限公司。“红玫”牌过滤嘴香烟:广州中烟工业有限公司。其它常规试剂:广州化学试剂厂。
4)实验仪器:PM型单腔非限制型小动物体描仪(1.0L):美国Buxco公司;数码摄影一体化系统:日本Nikon公司;0.6m×0.6m×1m香烟烟雾染毒箱:本实验室自制;A1003电子天平:德国Satorius公司;MDF-U53V-80℃低温冰箱:日本三洋公司;3-18K SIGMA高速冷冻离心机:美国Beckman公司;22G静脉留置针:苏州医疗器械有限公司;Anke TGL-16B型普通高速离心机:上海安停科学仪器厂;400型台式低温离心机:德国Heraeus公司;XW80A型旋涡振荡器:上海精密仪器仪表有限公司;DK8A恒温水浴锅:上海精宏试验仪器有限公司。
具体实施方式中所有数据用“均值±标准差”表示,各组间比较采用spss13.0进行单因素方差分析,方差齐用最小显著差异法(LSD),方差不齐或非正态的数据采用秩和检验,P<0.05表示差异有统计学意义。
实施例一:五味子总多糖对香烟烟雾刺激致咳嗽敏感性增高豚鼠的药理作用
1.1烟熏方法:豚鼠于实验前适应性安静饲养一周后,置于自制香烟染毒箱内,每次点燃10根香烟于烟熏槽内(烤烟型,焦油含量12mg,烟气烟碱含量1.1mg,烟气一氧化碳含量15mg),通过三通阀将香烟烟雾打入染毒箱内,自香烟燃完开始计时。每次熏烟20分钟,每天熏烟2次,每二次熏烟间隔时间大于6小时,连续熏烟14天。
1.2实验:
豚鼠完全随机分成正常组、模型组、溶剂对照组(0.5%的PEG400)、可待因组、水提取物高剂量组(剂量500mg/kg豚鼠/天,药物浓度50mg/mL)、总多糖高剂量组(剂量500mg/kg豚鼠/天,药物浓度50mg/mL)、总多糖中剂量组(剂量250mg/kg豚鼠/天,药物浓度25mg/mL)、总多糖低剂量组(剂量125mg/kg豚鼠/天,药物浓度12.5mg/mL)。
除正常组外,其余各组动物均采用上述1.1中的烟熏方法刺激。除正常组及可待因组外,其余各组豚鼠从烟熏第一天开始,于每天的第二次烟熏前2小时经口给予相应的药物或溶剂,连续14天。可待因组于柠檬酸咳嗽敏感性检查前1小时,经口给药(30mg/kg豚鼠,可待因浓度3mg/mL)。正常组正常饲养,不作任何处理。第15天将豚鼠置于体描箱内,适应2min后,雾化0.4mol/L柠檬酸水溶液进行咳嗽激发,10min后雾化结束,继续观察10min,记录自雾化开始的20min内豚鼠咳嗽次数及咳嗽潜伏期。
咳嗽激发实验24h后,3%戊巴比妥钠溶液(1mL/kg)腹腔注射麻醉动物,心脏取血10mL。取6mL0.1mol/L预冷的PBS缓冲液,分3次进行肺泡灌洗,统一灌洗左肺,每次反复灌洗3次,得肺泡灌洗液(Bronchoalveolar Lavage Fluid,BALF)。将所得BALF震荡混悬,抽取0.5mL,用红细胞裂解液充分裂解,3000转/分钟离心10分钟,取10μL上清液滴入血细胞计数板,光学显微镜下计算BALF炎症细胞总数(细胞总数/mL=(四大格细胞总数/4)×104/mL);抽取0.5mL后剩余的BALF于3000rpm离心10min,沉淀用1mLPBS混悬,取100μL制作细胞涂片,自然风干,浸泡于10%中性甲醛中过夜固定,取出后依次进行流水冲洗10min、苏木素染色15sec、流水冲洗1min、1%盐酸酒精脱色2sec、流水冲洗10min、伊红染色5sec、流水冲洗10min、烘干,得中性树胶封片,光学显微镜下连续随机抽取20个400倍视野进行连续计数,每张涂片连续计数400个细胞,计算其中中性粒细胞、嗜酸粒细胞、巨噬细胞、淋巴细胞的比例。
豚鼠抽取BALF后,从心脏注入50mLPBS进行灌洗,从气管注入2.5mL4%多聚甲醛,然后剪取一块右下肺组织及一段气管,10%中性甲醛固定24h以上。取出已固定好的肺组织,依次进行乙醇梯度脱水、生物透明剂处理、浸蜡、包埋、切片、脱蜡、梯度酒精水化、双蒸水短暂漂洗,最后进行HE染色后,中性树胶封片,进行病理观察。
实验结果:与正常组比较,各实验组豚鼠气道阻力未见明显差异,提示本实验建模方法未造成豚鼠气道阻力增加,有别于慢性阻塞性肺疾病动物模型。
各实验组豚鼠柠檬酸激发咳嗽次数见表1。结果表明,与模型组比较,总多糖(高、中剂量组)均显示出显著减少咳嗽次数的活性,而低剂量对咳嗽次数的抑制虽未达统计学意义,但有减少的趋势,表现出一定的剂量相关性;与模型组比较,水提取物高剂量组豚鼠咳嗽次数无显著差异。
表1各实验组对香烟烟雾刺激致咳嗽敏感性增高模型豚鼠的咳嗽次数影响(n=7~10)
注:与模型组比较,*P<0.05;**P<0.01;与水提取物高剂量组比较,#P<0.05;##P<0.01
各实验组咳嗽潜伏期见表2。结果表明,与模型组比较,总多糖高、中、低剂量均能显著延长咳嗽潜伏期,水提取物高剂量对咳嗽潜伏期的作用不明显。
表2各实验组对香烟烟雾刺激致咳嗽敏感性增高模型豚鼠的咳嗽潜伏期影响(n=7~10)
注:与模型组比较:*P<0.05,**P<0.01;与水提取物高剂量组比较:#P<0.05
BALF中炎症细胞总数及分类比较实验结果见表3。结果表明,与模型组比较,总多糖高、中、低剂量均能显著减少BALF中炎症细胞总数;总多糖的高、中剂量可显著减少BALF中中性粒细胞的比例。水提取物高剂量组豚鼠BALF细胞总数及细胞分类计数与模型组无显著差异。
表3各实验组对香烟烟雾刺激致咳嗽敏感性增高模型豚鼠的BALF炎症细胞总数和分类的影响(n=7~10)
注:与模型组比较:*P<0.05,**P<0.01;与水提取物高剂量组比较:#P<0.05,##P<0.01
病理切片观察结果表明,与模型组比较,总多糖各剂量组豚鼠肺组织及气管病理均明显改善:豚鼠细支气管周炎症细胞浸润明显减少,管腔内渗出减轻,肺泡间隔增宽程度减轻,提示五味子总多糖具有明显的减轻肺及气道炎症的作用。而水提取物高剂量组豚鼠肺组织及气管病理改善不明显。豚鼠肺组织及气管病理切片代表图见附图1。
实施例一的实验结果表明,五味子总多糖对香烟烟雾刺激致咳嗽敏感性增高豚鼠具有显著的降低咳嗽次数、延长咳嗽潜伏期、减轻肺及气道炎症的作用。
实施例二:
豚鼠静养一周后,进行咳嗽敏感性筛选:0.8mol/L柠檬酸雾化刺激1min,继续观察5min,记录自雾化开始6min内的咳嗽次数,大于10次小于50次的豚鼠为合格豚鼠。
将筛选合格的豚鼠完全随机分成正常组、溶剂对照组(0.5%的PEG400)、可待因组、水提取物高剂量组(剂量500mg/kg豚鼠/天,药物浓度50mg/mL)、总多糖高剂量组(剂量500mg/kg豚鼠/天,药物浓度50mg/mL)、总多糖中剂量组(剂量250mg/kg豚鼠/天,药物浓度25mg/mL)、总多糖低剂量组(剂量125mg/kg豚鼠/天,药物浓度12.5mg/mL)。
除正常组及可待因组外,其余各组豚鼠连续5天每天经口给予药物或溶剂,1次/天,第五日给药或溶剂后1h进行柠檬酸咳嗽激发:0.8mol/L柠檬酸雾化刺激1min,停止雾化,继续观察5min,记录自雾化开始6min内的咳嗽次数。可待因组于第5日柠檬酸咳嗽激发前1小时经口给药。正常组正常饲养,第五日直接进行柠檬酸激发。
各实验组的咳嗽次数如表4所示。结果表明,与正常组比较,总多糖高、中、低剂量干预组的豚鼠咳嗽次数均显著减少,水提取物高剂量干预组豚鼠咳嗽次数无显著差异。
表4各实验组对柠檬酸致急性咳嗽豚鼠的咳嗽次数影响(n=8)
注:与正常组比较:**P<0.01;与水提取物高剂量组比较:##P<0.01。
各实验组豚鼠的咳嗽潜伏期如表5所示。结果表明,与正常组比较,总多糖高、中、低剂量干预组豚鼠的咳嗽潜伏期均显著延长,水提取物高剂量干预组豚鼠咳嗽潜伏期无显著差异。
表5各实验组柠檬酸致急性咳嗽豚鼠的咳嗽潜伏期(n=8)
注:与正常组比较:*P<0.05,**P<0.01;与水提取物高剂量组比较:#P<0.05,##P<0.01。
实施例二的结果表明五味子总多糖能显著降低柠檬酸烟雾刺激致急性咳嗽豚鼠的咳嗽次数、延长咳嗽潜伏期,表现出治疗急性咳嗽方面的应用潜力。
实施例三
豚鼠静养一周后,进行咳嗽敏感性筛选:0.8mol/L柠檬酸雾化刺激1min,停止雾化,继续观察5min,记录自雾化开始6min内的咳嗽次数,大于10次小于50次的豚鼠为合格豚鼠。
筛选合格的豚鼠正常饲养3天后,随机分为4大组,每大组30只。第一大组随机分为3小组,每小组10只,均直接进行柠檬酸咳嗽激发:0.8mol/L柠檬酸雾化刺激1min,停止雾化,继续观察5min,记录自雾化开始6min内的咳嗽次数。第二大组随机分为3小组:正常组、可待因组(30mg/kg,经口给药)、五味子总多糖组(500mg/kg,药物浓度50mg/mL,经口给药),每小组10只,正常组直接进行柠檬酸咳嗽激发,可待因组和五味子总多糖组给药1小时后进行咳嗽激发,激发条件同第一大组;第三大组和第四大组的分组及激发条件均与第二大组相同,可待因组和五味子总多糖组给药时间分别为激发前3h和5h。结果如图2所示,表明五味子总多糖(500mg/kg)一次性给药1h后即能显著减少柠檬酸烟雾刺激致豚鼠急性咳嗽次数,并且在给药5h后仍能表现出显著的药效,而可待因在给药5h后咳嗽次数与正常组已无显著差异。
由实施例一至实施例三可知:五味子总多糖能显著延长香烟烟雾刺激致咳嗽敏感性增高豚鼠及柠檬酸烟雾刺激致急性咳嗽豚鼠的咳嗽潜伏期、减少咳嗽次数,显著减少香烟烟雾刺激致咳嗽敏感性增高豚鼠肺泡灌洗液中炎症细胞总数及中性粒细胞比例,病理切片观察提示五味子总多糖干预后豚鼠细支气管周炎症细胞浸润明显减少,管腔内渗出减轻,肺泡间隔增宽程度减轻,提示五味子总多糖对豚鼠的气道炎症具有显著的抑制作用。并且五味子总多糖的作用明显好于五味子水提取物,且呈一定量效关系,表现出镇咳、缓解咳嗽及消除气道炎症方面的应用前景。
实施例四(含有五味子总多糖的糖浆制备例)
取2kg五味子总多糖,用适量水溶解制成五味子总多糖溶液,备用;另取蔗糖2kg,加水煮沸,加入前面制备好的五味子总多糖溶液,及苯甲酸钠4g,混匀,静置,取上清液,加水至2000ml,混匀,制得五味子总多糖的糖浆。将糖浆进行分装,每瓶分装100mL。
服用方法:每天1~3次,每次10mL,病情严重者可酌情加量。
本实施例中,五味子总多糖采用前文的提取工艺制备,具体是:将五味子药材粉碎,粉碎后用石油醚脱脂,然后用8倍量水煎煮3次,所得煎煮液进行浓缩,浓缩液用80%乙醇沉淀、过滤、沉淀酶法脱蛋白、活性炭脱色,用80%乙醇反复洗涤后进行干燥,得五味子总多糖,经检测,以D-葡萄糖计,其多糖含量为89%。
应用例
实施例四制得的五味子总多糖糖浆经过临床实验,其中有慢性咳嗽患者12例和急性咳嗽患者11例,通过每日饮用实施例四制得的糖浆1~3次,每次10mL,连续服用1~2周,总有效率为100%,具体反馈结果可见下表。
病例 | 显效 | 有效 | 无效 |
急性咳嗽 | 8 | 3 | 0 |
慢性咳嗽 | 9 | 3 | 0 |
下面就其中3个典型病例进行详细介绍:
病例1:温某,男,50岁,咳嗽3个月左右,诊断为咳嗽高敏综合征,连续服用五味子总多糖糖浆一周,咳嗽敏感性显著减低,咳嗽次数显著减少。
病例2:习某,男25岁,咳嗽1个月左右,诊断为感染后咳嗽,服用五味子总多糖糖浆2瓶,服药第一天起效,咳嗽基本缓解。
病例3:孔某,女,46岁,咳嗽1个月左右,伴痰堵感,痰难咳出,诊断为感染后咳嗽,服用五味子总多糖糖浆2瓶,服药后第二天起效,咳嗽好转7成,加服1瓶后,咳嗽基本完全缓解。
病例4:余某,男,36岁,咳嗽1年左右,干咳为主,诊断为嗜酸性粒细胞性支气管炎,胃食管反流性咳嗽,服用五味子总多糖糖浆2瓶,服药第三天起效,咳嗽好转4成,加服2瓶后,咳嗽症状基本消除。
由上述实施例可知,仅通过口服五味子总多糖糖浆便能有效缓解咳嗽,减轻气道炎症。而且,五味子总多糖提取自中药五味子,五味子为卫生部公布的可用于保健食品的中药,对人体无任何毒性及副作用。五味子总多糖除了制成糖浆,本领域技术人员根据需要也可以采用现有制剂工艺将其制成药学上可接受的其他剂型,例如片剂、硬胶囊、软胶囊、散剂、酊剂、丸剂、颗粒剂、注射剂或其他口服液剂型等。
以上所述,仅是本发明的较佳实施例而已,并非对本发明做任何形式上的限制,故凡未脱离本发明技术方案的内容,依据本发明的技术实质对以上实施例所做的任何简单修改、等同变化与修饰,均仍属于本发明技术方案的范围内。
Claims (6)
1.五味子总多糖在制备用于治疗咳嗽的药物或保健品中的应用,其特征在于,所述药物或保健品为用于治疗急性、亚急性或慢性咳嗽的药物或保健品;所述五味子总多糖其制备过程为:
将五味子药材粉碎,粉碎后用石油醚脱脂,然后用8倍量水煎煮3次,所得煎煮液进行浓缩,浓缩液用80%乙醇沉淀、过滤、沉淀酶法脱蛋白、活性炭脱色,用80%乙醇反复洗涤后进行干燥,得五味子总多糖,经检测,以D-葡萄糖计,其多糖含量为89%。
2.根据权利要求1所述的应用,其特征在于,所述药物或保健品为用于镇咳、缓解咳嗽或消除气道炎症的药物或保健品。
3.根据权利要求1或2所述的应用,其特征在于,所述的五味子总多糖提取自五味子,所述五味子为五味子Schisandra chinensis(Turcz.)Baill.、华中五味子Schisandrasphenanthera Rehd.et Wils.中的至少一种。
4.根据权利要求1所述的应用,其特征在于,以D-葡萄糖计,所述的五味子总多糖其中的多糖含量为50~100%。
5.根据权利要求1所述的应用,其特征在于,所述五味子总多糖制成药学上可接受的剂型。
6.根据权利要求5所述的应用,其特征在于,所述剂型为片剂、硬胶囊、软胶囊、散剂、酊剂、口服液、糖浆、颗粒剂、丸剂或注射剂。
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410209951.XA CN103977019B (zh) | 2014-05-16 | 2014-05-16 | 五味子总多糖在制备用于治疗咳嗽的药物或保健品中的应用 |
PCT/CN2015/076064 WO2015172613A1 (zh) | 2014-05-16 | 2015-04-08 | 五味子总多糖在制备用于治疗咳嗽的药物或保健品中的应用 |
EP15793101.5A EP3144003B1 (en) | 2014-05-16 | 2015-04-08 | Application of fructus schisandrae total polysaccharides in preparation of medicine or nutraceuticals used for treating coughing |
US15/351,512 US9629869B2 (en) | 2014-05-16 | 2016-11-15 | Application of fructus schisandrae total polysaccharides in preparatoin of medicine or nutraceuticals used for treating coughing |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410209951.XA CN103977019B (zh) | 2014-05-16 | 2014-05-16 | 五味子总多糖在制备用于治疗咳嗽的药物或保健品中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103977019A CN103977019A (zh) | 2014-08-13 |
CN103977019B true CN103977019B (zh) | 2016-08-24 |
Family
ID=51269346
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410209951.XA Active CN103977019B (zh) | 2014-05-16 | 2014-05-16 | 五味子总多糖在制备用于治疗咳嗽的药物或保健品中的应用 |
Country Status (4)
Country | Link |
---|---|
US (1) | US9629869B2 (zh) |
EP (1) | EP3144003B1 (zh) |
CN (1) | CN103977019B (zh) |
WO (1) | WO2015172613A1 (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102202122B1 (ko) * | 2018-04-30 | 2021-01-13 | 주식회사 종근당 | 백출 및 오미자 추출물을 포함하는 진해거담 활성을 갖는 조성물 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101181354B (zh) * | 2007-11-26 | 2013-03-13 | 沈阳药科大学 | 五味子化学成分群提取物及其制备工艺 |
CN101361799B (zh) * | 2008-09-01 | 2011-07-20 | 北京世纪博康医药科技有限公司 | 一种含有褐藻多糖硫酸酯和五味子的组合物和其应用 |
CN103263491A (zh) * | 2013-03-29 | 2013-08-28 | 阚兆云 | 中药组合物 |
CN103230465A (zh) * | 2013-04-08 | 2013-08-07 | 张宗升 | 中药提取物 |
CN104138450B (zh) * | 2014-08-07 | 2016-08-03 | 广州医科大学附属第一医院 | 用于治疗咳嗽及减轻气道炎症的五味子提取物、其制备方法及应用 |
-
2014
- 2014-05-16 CN CN201410209951.XA patent/CN103977019B/zh active Active
-
2015
- 2015-04-08 EP EP15793101.5A patent/EP3144003B1/en active Active
- 2015-04-08 WO PCT/CN2015/076064 patent/WO2015172613A1/zh active Application Filing
-
2016
- 2016-11-15 US US15/351,512 patent/US9629869B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
US20170056431A1 (en) | 2017-03-02 |
EP3144003B1 (en) | 2022-02-16 |
EP3144003A1 (en) | 2017-03-22 |
EP3144003A4 (en) | 2018-02-07 |
CN103977019A (zh) | 2014-08-13 |
US9629869B2 (en) | 2017-04-25 |
WO2015172613A1 (zh) | 2015-11-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2856592C (en) | Vicenin 2 and analogues thereof for use as an antispasmodic and/or prokinetic agent | |
US10744152B2 (en) | Application of Asarum total polysaccharides in preparation of medicine for treating cough | |
CN109106760A (zh) | 肉苁蓉苯乙醇苷改善睡眠的新用途及其应用 | |
CN104042720B (zh) | 具有防治糖尿病并发抑郁症的中药及其应用 | |
CN104138450B (zh) | 用于治疗咳嗽及减轻气道炎症的五味子提取物、其制备方法及应用 | |
CN103977019B (zh) | 五味子总多糖在制备用于治疗咳嗽的药物或保健品中的应用 | |
Ninave et al. | Pharmacological screening of Acalypha indica L.: Possible role in the treatment of asthma | |
CN102670977B (zh) | 一种治疗痹症的中药组合物及其制备方法和用途 | |
CN102178721B (zh) | 绞股蓝混悬液、提取物在制备治疗抗抑郁症药物中的应用 | |
CN103977076B (zh) | 五味子总木脂素在制备用于治疗咳嗽的药物中的应用 | |
CN104490965B (zh) | 竹节参多糖、竹节参总皂苷及竹节参皂苷v的应用 | |
CN104095912B (zh) | 治疗风湿骨病的中成药的制备方法 | |
CN105327115A (zh) | 一种防治ⅱ型糖尿病桑黄通泻配方及制备工艺 | |
CN104398898A (zh) | 一种用于更年期甲亢离子透入剂的制备方法 | |
CN104840737A (zh) | 具有补气润肺作用的中药组合物及其制备方法和应用 | |
CN104688939B (zh) | 治疗慢性阻塞性肺病的中药组合物及其制备方法 | |
CN104524266A (zh) | 一种治疗儿童甲亢的离子导入剂的制备方法 | |
CN107041923A (zh) | 一种具有清肺、止咳、化痰功能的组合物及其制备方法 | |
Cun et al. | Application of dopamine combined with dobutamine in children with pneumonia and heart failure. | |
CN103610845A (zh) | 一种治疗小儿慢性咳嗽的药物的制备方法 | |
CN113940944A (zh) | 一种用于慢性咽炎的中药有效成分的组合制剂 | |
CN105535724A (zh) | 一种治疗慢性支气管炎的中药制剂及其制备方法 | |
CN104873779A (zh) | 一种治疗造影剂肾病的中药及制备方法 | |
CN105597051A (zh) | 一种防治小儿肠道寄生虫的中药制剂 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant |