CN100349590C - Medicinal use of glutinous rehmannia stem and leaf and its extract for preventing asthma and anti-allergy - Google Patents
Medicinal use of glutinous rehmannia stem and leaf and its extract for preventing asthma and anti-allergy Download PDFInfo
- Publication number
- CN100349590C CN100349590C CNB2004100622468A CN200410062246A CN100349590C CN 100349590 C CN100349590 C CN 100349590C CN B2004100622468 A CNB2004100622468 A CN B2004100622468A CN 200410062246 A CN200410062246 A CN 200410062246A CN 100349590 C CN100349590 C CN 100349590C
- Authority
- CN
- China
- Prior art keywords
- stem
- glutinous
- rehmannic
- leaf
- extract
- 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.)
- Expired - Fee Related
Links
- 208000006673 asthma Diseases 0.000 title claims abstract description 42
- 239000000284 extract Substances 0.000 title claims abstract description 40
- 230000003266 anti-allergic effect Effects 0.000 title abstract description 3
- 241000405414 Rehmannia Species 0.000 title abstract 6
- 239000003814 drug Substances 0.000 claims abstract description 37
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 4
- 201000010105 allergic rhinitis Diseases 0.000 claims description 4
- 201000009961 allergic asthma Diseases 0.000 claims 3
- 238000002481 ethanol extraction Methods 0.000 claims 3
- 239000000401 methanolic extract Substances 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 15
- 229940079593 drug Drugs 0.000 abstract description 13
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 7
- 229930182470 glycoside Natural products 0.000 abstract description 5
- 150000002338 glycosides Chemical class 0.000 abstract description 5
- 206010020751 Hypersensitivity Diseases 0.000 abstract 3
- 208000026935 allergic disease Diseases 0.000 abstract 3
- 230000007815 allergy Effects 0.000 abstract 3
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- 230000001741 anti-phlogistic effect Effects 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 33
- 241001465754 Metazoa Species 0.000 description 27
- 239000000287 crude extract Substances 0.000 description 26
- 206010070834 Sensitisation Diseases 0.000 description 18
- 238000002386 leaching Methods 0.000 description 18
- 230000008313 sensitization Effects 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 241000700199 Cavia porcellus Species 0.000 description 16
- 108010058846 Ovalbumin Proteins 0.000 description 16
- 229940092253 ovalbumin Drugs 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 239000007924 injection Substances 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- QIIDATRCGITYRZ-UHFFFAOYSA-N Catalpol Natural products OCC1OC(OC2OC=CC3C(O)C(=C(CO)C23)O)C(O)C(O)C1O QIIDATRCGITYRZ-UHFFFAOYSA-N 0.000 description 12
- LHDWRKICQLTVDL-PZYDOOQISA-N catalpol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@@H]2[C@@]3(CO)O[C@H]3[C@@H](O)[C@@H]2C=CO1 LHDWRKICQLTVDL-PZYDOOQISA-N 0.000 description 12
- UXSACQOOWZMGSE-UHFFFAOYSA-N catalposide Natural products OC1C(O)C(O)C(CO)OC1OC1C2C3(CO)OC3C(OC(=O)C=3C=CC(O)=CC=3)C2C=CO1 UXSACQOOWZMGSE-UHFFFAOYSA-N 0.000 description 12
- 238000011534 incubation Methods 0.000 description 12
- 210000000627 locus coeruleus Anatomy 0.000 description 12
- LHDWRKICQLTVDL-UHFFFAOYSA-N methyl iridoid glycoside Natural products OC1C(O)C(O)C(CO)OC1OC1C2C3(CO)OC3C(O)C2C=CO1 LHDWRKICQLTVDL-UHFFFAOYSA-N 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 238000000605 extraction Methods 0.000 description 10
- 210000002683 foot Anatomy 0.000 description 10
- 230000036541 health Effects 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000443 aerosol Substances 0.000 description 8
- 239000013566 allergen Substances 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 7
- 230000000144 pharmacologic effect Effects 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- NYCXYIWXBJWWIL-PZYDOOQISA-N (2s,3r,4s,5s,6r)-2-[[(1as,1bs,2s,5ar,6s,6as)-6-hydroxy-1a-(hydroxymethyl)-2,4,5,5a,6,6a-hexahydro-1bh-oxireno[5,6]cyclopenta[1,3-c]pyran-2-yl]oxy]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@@H]2[C@@]3(CO)O[C@H]3[C@@H](O)[C@@H]2CCO1 NYCXYIWXBJWWIL-PZYDOOQISA-N 0.000 description 6
- YOOQXBIEVFLKNS-UHFFFAOYSA-N Acetylcatalpol Natural products CC(=O)OCC12OC1C(O)C3C=COC(OC4OC(CO)C(O)C(O)C4O)C23 YOOQXBIEVFLKNS-UHFFFAOYSA-N 0.000 description 6
- 206010002198 Anaphylactic reaction Diseases 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 239000000048 adrenergic agonist Substances 0.000 description 6
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 6
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 6
- 230000036783 anaphylactic response Effects 0.000 description 6
- 208000003455 anaphylaxis Diseases 0.000 description 6
- NYCXYIWXBJWWIL-UHFFFAOYSA-N dihydrocatalpol Natural products OC1C(O)C(O)C(CO)OC1OC1C2C3(CO)OC3C(O)C2CCO1 NYCXYIWXBJWWIL-UHFFFAOYSA-N 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 210000003491 skin Anatomy 0.000 description 6
- 230000008961 swelling Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 229930182489 iridoid glycoside Natural products 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 230000001629 suppression Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 102000009660 Cholinergic Receptors Human genes 0.000 description 4
- 108010009685 Cholinergic Receptors Proteins 0.000 description 4
- ZUKLFFYDSALIQW-MSUKCBDUSA-N Iridoid glycoside Chemical compound [H][C@]12CC[C@H](C(O)=O)[C@@]1([H])[C@H](OC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)OC=C2 ZUKLFFYDSALIQW-MSUKCBDUSA-N 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- 230000002052 anaphylactic effect Effects 0.000 description 4
- 230000001088 anti-asthma Effects 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 239000006286 aqueous extract Substances 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 230000003203 everyday effect Effects 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 239000003862 glucocorticoid Substances 0.000 description 4
- 239000007927 intramuscular injection Substances 0.000 description 4
- 238000010255 intramuscular injection Methods 0.000 description 4
- 229930182487 phenolic glycoside Natural products 0.000 description 4
- 150000007950 phenolic glycosides Chemical class 0.000 description 4
- 239000008517 radix Trichosanthis Substances 0.000 description 4
- 230000029058 respiratory gaseous exchange Effects 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- DTNSOISBYQKHCS-XTOBSYSVSA-N (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-[[(1S,2S,4S,5S,6R,10S)-5-hydroxy-2-(hydroxymethyl)-3,9-dioxatricyclo[4.4.0.02,4]dec-7-en-10-yl]oxy]oxan-2-yl]methoxy]oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]3[C@@]4(CO)O[C@H]4[C@@H](O)[C@@H]3C=CO2)O1 DTNSOISBYQKHCS-XTOBSYSVSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000384 rearing effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 2
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 2
- 206010048768 Dermatosis Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- VDWSYBFEQXWINA-UHFFFAOYSA-N Martinoside Natural products C1=C(O)C(OC)=CC=C1CCOC1C(O)C(OC2C(C(O)C(O)C(C)O2)O)C(OC(=O)C=CC=2C=C(O)C(OC)=CC=2)C(CO)O1 VDWSYBFEQXWINA-UHFFFAOYSA-N 0.000 description 2
- 108010003541 Platelet Activating Factor Proteins 0.000 description 2
- 206010040914 Skin reaction Diseases 0.000 description 2
- WLWAYPFRKDSFCL-CNMJWYMJSA-N [(2r,3r,4r,5r,6r)-5-hydroxy-6-[2-(3-hydroxy-4-methoxyphenyl)ethoxy]-2-(hydroxymethyl)-4-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-3-yl] (e)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate Chemical compound C1=C(O)C(OC)=CC=C1CCO[C@H]1[C@H](O)[C@@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@H](OC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)[C@@H](CO)O1 WLWAYPFRKDSFCL-CNMJWYMJSA-N 0.000 description 2
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 2
- 238000011047 acute toxicity test Methods 0.000 description 2
- 208000028004 allergic respiratory disease Diseases 0.000 description 2
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 2
- FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical class NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 229940124623 antihistamine drug Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229960004495 beclometasone Drugs 0.000 description 2
- 239000000168 bronchodilator agent Substances 0.000 description 2
- 210000005252 bulbus oculi Anatomy 0.000 description 2
- RLGRBYHBNWLGER-UHFFFAOYSA-N cistanoside D Natural products C1=C(O)C(OC)=CC(CCOC2C(C(OC3C(C(O)C(O)C(C)O3)O)C(OC(=O)C=CC=3C=C(OC)C(O)=CC=3)C(CO)O2)O)=C1 RLGRBYHBNWLGER-UHFFFAOYSA-N 0.000 description 2
- 229960000265 cromoglicic acid Drugs 0.000 description 2
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 2
- 230000035617 depilation Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- ZMYQRHSOVRDQDL-NSWBACJASA-N leucosceptoside A Natural products COc1cc(C=CC(=O)O[C@@H]2[C@@H](CO)O[C@@H](OCCc3ccc(O)c(O)c3)[C@H](O)[C@H]2O[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)ccc1O ZMYQRHSOVRDQDL-NSWBACJASA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- WLWAYPFRKDSFCL-AYPSUWEUSA-N martynoside Natural products COc1ccc(CCO[C@@H]2O[C@H](CO)[C@@H](OC(=O)C=Cc3ccc(O)c(OC)c3)[C@H](O[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@H]2O)cc1O WLWAYPFRKDSFCL-AYPSUWEUSA-N 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 201000004335 respiratory allergy Diseases 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 230000035483 skin reaction Effects 0.000 description 2
- 231100000430 skin reaction Toxicity 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 206010003645 Atopy Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000013557 Plantaginaceae Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229940122117 Potassium channel agonist Drugs 0.000 description 1
- 208000018569 Respiratory Tract disease Diseases 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000002804 anti-anaphylactic effect Effects 0.000 description 1
- 210000000544 articulatio talocruralis Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000023819 chronic asthma Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 150000008145 iridoid glycosides Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 229930003658 monoterpene Natural products 0.000 description 1
- 150000002773 monoterpene derivatives Chemical class 0.000 description 1
- 235000002577 monoterpenes Nutrition 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 201000004647 tinea pedis Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to the application of rehmannia stems and leaves and rehmannia stem and leaf extracts in the preparation of medicines for treating and preventing asthma, chronic obstructive pulmonary diseases and allergy diseases. The rehmannia stems and leaves, the rehmannia stem and leaf extracts and rehmannia stem and leaf total glycosides have obvious antiphlogistic, antiallergic and antasthmatic activity, are natural medicines for treating and preventing asthma, chronic obstructive pulmonary diseases and allergy diseases, and have no toxic or side effect of the existing medicines for treating asthma, chronic obstructive pulmonary diseases and allergy diseases.
Description
Technical field
The present invention relates to field of medicaments, a kind of medical usage that effectively prevents and treat the natural plant extracts of asthma, chronic obstructive pulmonary disease (COPD), irritated disease.The present invention is specially adapted to treatment and prevention of asthma.Also can be used for treatment and Polyglucan rhinitis and anaphylaxis dermatosis.
Background technology
Asthma is the respiratory tract anaphylaxis reactive inflammation disease that allergen causes.Allergen is the key factor that causes pathogenesis of asthma and development, and allergen is deposited on the air flue mucosa after sucking air flue, causes airway allergy inflammation by local and systemic immune response.Sucking allergen causes airway allergy inflammation branch sensitization and causes scorching two stages.Atopy patient produces sensitization after beginning to suck certain allergen, and body can be sensitiveness to this allergen.In the sensitization stage, it is that air flue produces and the corresponding specificity antibody IgE of allergen that body mainly changes, mastocyte in this antibody IgE and the air flue, acidophil and hugely have a liking for cell affinity is all arranged, these interior cells of these specificity antibody IgEs and air flue combine the sensitization state that has formed air flue and body.Can cause activation and release inflammatory mediators such as mastocyte when identical allergen sucks air flue once more, cause air flue allergenicity inflammation and cause asthma attack, Here it is causes the scorching stage.It also is the pathogenic process of asthma.
Bronchial asthma is chronic respiratory tract disease the most common in the world wide, and the conservative estimation whole world has at least the people more than 100,000,000 to suffer from asthma, in recent years, and because of its prevalence and mortality rate all are taking advantage of a favourable situation of rising.Asthma has become serious public health problem and has received the very big concern of countries in the world.Therefore need provide the medicine and the method for the treatment of asthma effectively.
In the last thirty years, a large amount of development and researches has been carried out to the medicine of treatment asthma in the whole world.The medicine of the treatment asthma that has developed has β
2-3 adrenergic receptor agonists class, alpha-adrenergic aceptor antagonist class, aminophylline class, cholinoceptor antagonist class, calcium ion antagonist class, potassium-channel agonist, glucocorticoid, cell membrane stability agent (sodium cromoglicate, Buddhist nun examine a meter sodium more), antihistamine drug, LTRA, platelet activating factor (PAF) antagonist, specific active immunotherapy agent, nonspecific immunity therapeutic agent etc.Asthma is the very complicated multi-factor disease of a kind of mechanism, is the diseases associated with inflammation that the many cells multimedium participates in.Above-mentioned these medicines (perhaps Therapeutic Method) mechanism of action single (to a kind of or two, three kind of medium, the factor, receptor or passage work), these medicines or therapeutic effect not obvious or oral invalid must the special pathway administration or side effect greatly can't life-time service.What generally adopt clinically at present also is that the most effective Therapeutic Method is to suck glucocorticoid (light moderate sucks sodium cromoglicate, the Buddhist nun examines a meter sodium more) anti-inflammatory treatment for a long time, sucks β during asthma attack
2Bronchodilators such as-3 adrenergic receptor agonists, cholinoceptor antagonist.These Therapeutic Method are to relieving asthma symptoms, and there is certain effect the quality of life of improving asthma patient, but the M ﹠ M of asthma is decreased.Reduce the M ﹠ M of asthma, the prognosis that improves asthma still lack effective means (Li Minghua etc., asthma, the People's Health Publisher, 1998, p2).The treatment asthma needs more effective and safer medicine.
The cause of disease of chronic obstructive pulmonary disease is at present also not clear, but relevant with airway inflammation be sure, use long-term glucocorticoid anti-inflammatory treatment and the suction β of sucking at present
2The treatment of bronchodilators such as-3 adrenergic receptor agonists, cholinoceptor antagonist is that certain effect is arranged.But the therapeutic effect of these medicines is not very good, and the medicine of seeking more effective treatment chronic obstructive pulmonary disease is very important.
Summary of the invention
The present invention relates to treat the Chinese medicine pharmaceutical composition of asthma and other anaphylactic disease, particularly with Chinese medicine glutinous rehmannic stem and leaf and the iridoids that contained thereof natural medicinal formulations for its effective ingredient.
Glutinous rehmannic stem and leaf is the aquatic foods product or the dry product of scrophulariaceae rehmannia glutinosa plant Rehmannia glutinosa Libsch. aerial parts, and Radix Rehmanniae is mainly the cultivation product, and wild hillside and wasteland, roadside in height above sea level 50-1100 rice also arranged.Be distributed in ground such as Liaoning, the Inner Mongol, Hebei, Henan, Shanxi, Shaanxi, Shandong, Anhui, Zhejiang, Hubei, Hunan, Sichuan.The document record contains number of chemical compositions such as iridoid glycosides, monoterpene and glycosides thereof, phenolic glycoside, organic acid, polysaccharide, aminoacid, sterol in the glutinous rehmannic stem and leaf, reach 20 kinds of metallic elements such as calcium, magnesium, potassium, ferrum, zinc, manganese.
" Chinese medicine voluminous dictionary " record, Semen Rehmanniae (seed of Radix Rehmanniae) " Bencao Tujing ": " dry in the shade and smash the end, water clothes tool for weighing medicine in ancient China, taking medicine three times daily, merit and Radix Rehmanniae etc. ".Folium Rehmanniae is controlled malignant boil, hands, tinea pedis.Fols Rehmanniae is controlled and is quenched one's thirst, lumbago due to renal deficiency.All there is not the record of treatment asthma and anaphylactic disease.
Be used to prepare the glutinous rehmannic stem and leaf of the glutinous rehmannic stem and leaf total heteroside extract of treatment asthma, treatment chronic obstructive pulmonary disease, anaphylactic disease, comprise the Radix Rehmanniae seed of aerial parts of Radix Rehmanniae and/or the natural drying product of glutinous rehmannic stem and leaf and/or Fols Rehmanniae.
The purpose of this invention is to provide the application in the pharmaceutical preparation of preparation treatment asthma, treatment chronic obstructive pulmonary disease, anaphylactic disease and diseases associated with inflammation of glutinous rehmannic stem and leaf and glutinous rehmannic stem and leaf extract thereof.The glutinous rehmannic stem and leaf extract extracts from glutinous rehmannic stem and leaf, comprises water extract, alcohol extract, the water-alcohol extraction of glutinous rehmannic stem and leaf, and the material that extracts from glutinous rehmannic stem and leaf with other solvent.Especially, be meant that the glutinous rehmannic stem and leaf iridoids chemical constituent that contains that extracts is the glutinous rehmannic stem and leaf total heteroside extract of effective ingredient from glutinous rehmannic stem and leaf, glutinous rehmannic stem and leaf total heteroside extract mainly is made up of following chemical constituent: catalpol (catalpol), Martynoside. A, D (rehmannioside A, D), acetylcatalpol (acetylcatalpol), dihydro catalpol (dihydrocatalpol etc., and other iridoid constituents, phenolic glycoside and other micro constitutent, and be main effective ingredient with catalpol.Especially, described glutinous rehmannic stem and leaf total heteroside extract total glycosides content can be not less than 50%, and catalpol content can be not less than 20%.
Characteristics such as the glutinous rehmannic stem and leaf extract is a kind of have treatment asthma, treatment chronic obstructive pulmonary disease, active plant extract of antiallergic pharmacology, and it is little to have toxicity, and the life-time service curative effect is preferable.
The Wistar healthy mice is used in the acute toxicity test of glutinous rehmannic stem and leaf extract, and oral maximum dosage-feeding is equivalent to not see animal dead more than the glutinous rehmannic stem and leaf crude drug 150g/kg; Intraperitoneal injection LD
50Be equivalent to crude drug 50/kg, intravenous administration LD
50Be 25～39g/kg.
Iridoid glycoside content is greater than 50%, and catalpol content is done acute toxicity test greater than 20% glutinous rehmannic stem and leaf total heteroside extract with the Wistar healthy mice, and oral maximum dosage-feeding is 59.7g/kg, does not see animal dead; Intraperitoneal injection LD
50Be 19.6～27.8g/kg, intravenous administration LD
50Be 2.77～3.45g/kg.
Glutinous rehmannic stem and leaf total heteroside extract provided by the invention can mix with one or more pharmaceutically acceptable stone compositions, and contains in the compositions of glutinous rehmannic stem and leaf total heteroside extract and further contain β
2-3 adrenergic receptor agonists.
The invention provides the method that the treatment mammal breathes the immune-mediated inflammatory diseases in road, described method comprises the glutinous rehmannic stem and leaf total heteroside extract to described administration treatment effective dose, or use the pharmaceutical composition that contains glutinous rehmannic stem and leaf total heteroside extract, or further contain β
2The described compositions of-3 adrenergic receptor agonists.
The pharmaceutical composition of glutinous rehmannic stem and leaf total heteroside extract can be a various forms, comprises peroral dosage form, the solution of suction form and injectable and infusion.When using with inhalant or aerosol form, glutinous rehmannic stem and leaf total heteroside extract is used in combination with the dry powder that pharmaceutically acceptable carrier solution maybe can change into the form of aerosol.Similarly, when using with oral administration, glutinous rehmannic stem and leaf total heteroside extract is used in combination with the pharmaceutically acceptable carrier that is used in oral administration.When being used for the treatment of immune-mediated inflammatory dermatosis, glutinous rehmannic stem and leaf total heteroside extract can be used in combination with nontoxic, pharmaceutically acceptable topical vehicle.Glutinous rehmannic stem and leaf total heteroside extract can with the treating asthma agent, as β
2-3 adrenergic receptor agonists, cholinoceptor antagonist, aminophylline class, glucocorticoid, antihistamine drug etc. are used in combination.
Glutinous rehmannic stem and leaf total heteroside extract is used to prevent and treat immune-mediated inflammatory diseases, particularly comprises the disease relevant with respiratory tract of asthma, and particularly relevant with chronic asthma immunne response is crossed strong and allergic rhinitis.Therefore the present invention also provides the method for the treatment of immune-mediated disease, and this method comprises to the glutinous rehmannic stem and leaf total heteroside extract that has immune-mediated inflammatory diseases patient with treatment effective dosage forms and dosage.
Glutinous rehmannic stem and leaf total heteroside extract is used for prevention and treatment chronic obstructive pulmonary disease.
The dosage of glutinous rehmannic stem and leaf extract of the present invention, because of patient's state, body weight, administering mode etc. different different.Such as under non-oral situation, intramuscular, vein, enteral administration, calculate 0.20mg-2000mg/kg. day with the glutinous rehmannic stem and leaf crude drug, preferred 2.0mg-200mg/kg. day, calculate 2.0-20g/kg. day with the glutinous rehmannic stem and leaf crude drug under the oral situation, preferred 20-2000mg/kg. day.
Iridoid glycoside content of the present invention is greater than 50%, and catalpol content is greater than the dosage of 20% glutinous rehmannic stem and leaf total heteroside extract, because of patient's state, body weight, administering mode etc. different different.Such as under non-oral situation, intramuscular, vein, enteral administration 0.01mg-100mg/kg. day, preferred 0.1mg-10mg/kg. day, 0.1-1000mg/kg. day under the oral situation, preferred 1-100mg/kg. day.
The specific embodiment
With following embodiment the present invention is specified, but the present invention is not limited to the content that the following example comprises.
[embodiment one] gets glutinous rehmannic stem and leaf 20kg, water boils for 160 liters and extracted 1 hour, leaching extracting solution, medicinal residues add 120 liters in water again and boil extraction 2 hours, leaching extracting solution, medicinal residues add 120 liters in water again and boil extraction 2 hours, the leaching extracting solution merges aqueous extract, vacuum concentration to 20 liter, get the glutinous rehmannic stem and leaf extracting solution, place refrigerator to preserve.
The clinical research of glutinous rehmannic stem and leaf extracting solution treatment asthma
1, case is selected 60 examples, male 30 examples, and women 30 examples, age 16-60 year, (People's Health Publisher, 1998, standard diagnostics p165) was the bronchial asthma patient according to chief editor'ss " asthma " such as Li Minghua.Be divided into 2 groups at random, every group 30 example, male 15 examples, women 15 examples; The A group is the treatment group, and B is a matched group.2, Therapeutic Method, the treatment group is oral with the glutinous rehmannic stem and leaf extracting solution, and every day 3 times, each 10ml took 30 days continuously; The matched group propionic acid beclometasone aerosol, every day 2 times, each 200 μ g took 30 days continuously.3, therapeutic outcome, when treatment finished, the treatment group was cured 20 examples, effective 10 examples; Matched group is cured 9 examples, effective 21 examples.Treatment finishes back 1 month, and the treatment group is cured 13 examples, effective 13 examples; Matched group is cured 5 examples, effective 17 examples.
[embodiment two] get glutinous rehmannic stem and leaf 2kg, water 16000ml boils and extracted 1 hour, the leaching extracting solution, medicinal residues add water 12000ml again and boil extraction 1 hour, and leaching extracting solution, medicinal residues add water 12000ml again and boil extraction 1 hour, the leaching extracting solution, merge aqueous extract, vacuum concentration gets glutinous rehmannic stem and leaf crude extract (1) 632g to doing.
The ovalbumin aerosol sucks to draw breathes heavily test
Get 60 of 200-250g Cavia porcelluss, male and female half and half, prior to right rear leg outside intramuscular injection 4% ovalbumin normal saline solution 0.2ml/ only, while lumbar injection 4% gel aluminum hydroxide 0.2ml sensitization.From sensitization second day, animal was divided into 2 groups at random: matched group, treatment group (4.0g/kg).Treatment group glutinous rehmannic stem and leaf crude extract (1) 4.0g/kg gastric infusion, totally 14 days, behind the last medicine, animal is put in the airtight glass bell jar, after treating peace and quiet, start air compressor, spray into 30 seconds of 3.5% ovalbumin normal saline, observe incubation period and the number of animals that tic takes place that the tic of panting property appears in Cavia porcellus in 6 minutes with the constant voltage of 53kPa (400mmHg).(Xu Shuyun, Bian Rulian, Chen Xiu chief editor, pharmacological experimental methodology, the People's Health Publisher, in November, 1991 second edition, 1199 pages).
Table 1, glutinous rehmannic stem and leaf crude extract (1) are drawn the influence that Cavia porcellus breathes heavily to medicine
| Group | Number of animals (n) | Dosage (g/kg) | Draw and breathe heavily incubation period (second) | Tic number of animals (only) |
| Contrast glutinous rehmannic stem and leaf crude extract (1) | 10 10 | - 4.0 | 60.7±29.7 150.5±96.8 * | 10/10 9/10 |
Annotate: relatively think significant difference in P＜0.05 with the blank group, (with
*Expression).
Result of the test shows, glutinous rehmannic stem and leaf crude extract (1) 4.0g/kg dosage can draw the incubation period of breathing heavily Cavia porcellus by significant prolongation ovalbumin normal saline solution, compare with matched group that there were significant differences (P＜0.05), show that glutinous rehmannic stem and leaf crude extract (1) has certain antiasthmatic effect.
Passive cutaneous anaphylaxis test (PCA)
The rat body is divided into 2 groups at random by heavy, 10/group, ♀ ♂ half and half, sub-cage rearing, 5/cage.Be respectively blank group, reagent group 4.0g/kg.d.Therapeutic administration glutinous rehmannic stem and leaf crude extract (1) 4.0g/kg.d is adopted in test, successive administration glutinous rehmannic stem and leaf crude extract (1) 14d before antigen is attacked.
Antiserum Preparation: with four sole injections of above-mentioned Radix Trichosanthis aluminium hydroxide suspension, every sole injection 0.1ml, 0.4ml altogether.The 10-15d maturation, the about 10ml of eyeball blood-letting with the centrifugal 15min of 3000 commentaries on classics/min, gets upper serum and promptly gets antiserum.
Passive sensitization of skin: will test and respectively organize the rat back depilation, 2 points are respectively got apart from center line 1.5cm in the spinal column both sides, every some interval 2cm, the about 1 * 1cm2 of area, totally 4 points.In skin of back, inject sero-fast different dilution factors (1: 30 1: 40) respectively.Carrying out quantitative corresponding antigens behind the 48h attacks.The tail vein injection Radix Trichosanthis adds AZO-blue solution 1mg/kg, sacrificed by decapitation behind the 30min.
Observation index: the sero-fast local skin reaction of intradermal injection, and measure the locus coeruleus diameter that AZO-blue is oozed out.Calculate PCA and suppress percentage rate (%).PCA suppress percentage rate=(blank group locus coeruleus diameter-medication group locus coeruleus diameter)/blank group locus coeruleus diameter * 100% (Xu Shuyun, Bian Rulian, the Chen Xiu chief editor, pharmacological experimental methodology, the People's Health Publisher, in November, 1991 second edition, 1197 pages)
Table 2, glutinous rehmannic stem and leaf crude extract (1) are to models of passive skin irritability of rats reaction influence
| Group | Number of animals (only) | Dosage mg/kg | Different serum-concentration locus coeruleus diameters (cm) | |
| 1∶30 | 1∶40 | |||
| Blank glutinous rehmannic stem and leaf crude extract (1) | 10 10 | Water 150.0 | 1.55±0.23 0.98±0.23 *** | 0.91±0.22 0.55±0.20 ** |
Annotate:
*Compare P＜0.01 with the blank group,
* *Compare P＜0.001 with the blank group
Result of the test sees Table 1.From table the result as can be seen, reagent glutinous rehmannic stem and leaf crude extract (1) is antiserum dilution factor 1: 30,1: 40 o'clock, show significance and suppress locus coeruleus diameter (P＜0.01), suppression ratio is 36.8% and 39.6%.Show that glutinous rehmannic stem and leaf crude extract (1) has certain inhibitory action to passive cutaneous anaphylaxis, PCA.
[embodiment three] get glutinous rehmannic stem and leaf 1kg, ethanol water 8000ml reflux, extract, with 70% 1 hour, the leaching extracting solution, medicinal residues added 70% ethanol water 6000ml reflux, extract, 1 hour again, and leaching extracting solution, medicinal residues added 70% ethanol water 6000ml reflux, extract, 1 hour again, the leaching extracting solution, merge extractive liquid,, vacuum concentration gets glutinous rehmannic stem and leaf crude extract (2) 230g to doing.
The ovalbumin aerosol sucks to draw breathes heavily test
Get 60 of 200-250g Cavia porcelluss, male and female half and half, prior to right rear leg outside intramuscular injection 4% ovalbumin normal saline solution 0.2ml/ only, while lumbar injection 4% gel aluminum hydroxide 0.2ml sensitization.From sensitization second day, animal is divided into 2 groups at random: matched group, treatment group, treatment group glutinous rehmannic stem and leaf crude extract (2) 2.5g/kg gastric infusion, totally 14 days, behind the last medicine, animal is put in the airtight glass bell jar, after treating peace and quiet, start air compressor, spray into 30 seconds of 3.5% ovalbumin normal saline, observe incubation period and the number of animals that tic takes place that the tic of panting property appears in Cavia porcellus in 6 minutes with the constant voltage of 53kPa (400mmHg).(chief editor such as Xu Shuyun, pharmacological experimental methodology, People's Health Publisher, second edition in 1991,1199 pages)
Table 3, glutinous rehmannic stem and leaf crude extract (2) are drawn the influence that Cavia porcellus breathes heavily to medicine
| Group | Number of animals n | Dosage (g/kg) | Draw and breathe heavily incubation period (second) | Tic number of animals n |
| Contrast glutinous rehmannic stem and leaf crude extract (2) | 10 10 | - 2.5 | 58.9±30.6 150.5±100.7 * | 10/10 9/10 |
Annotate: relatively think significant difference in P＜0.05 with the blank group, (with
*Expression).
Result of the test shows, glutinous rehmannic stem and leaf crude extract (2) 2.5g/kg dosage can draw the incubation period of breathing heavily Cavia porcellus by significant prolongation ovalbumin normal saline solution, compare with matched group that there were significant differences (P＜0.05), show that glutinous rehmannic stem and leaf crude extract (2) has certain antiasthmatic effect.
[embodiment four] get glutinous rehmannic stem and leaf 1kg, with methanol 8000ml reflux, extract, 1 hour, the leaching extracting solution, medicinal residues add methanol 6000ml again and boil extraction 1 hour, and leaching extracting solution, medicinal residues add methanol 6000ml reflux, extract, 1 hour again, the leaching extracting solution, merge extractive liquid,, vacuum concentration gets glutinous rehmannic stem and leaf crude extract (3) 216g to doing.
The ovalbumin aerosol sucks to draw breathes heavily test
Get 60 of 200-250g Cavia porcelluss, male and female half and half, prior to right rear leg outside intramuscular injection 4% ovalbumin normal saline solution 0.2ml/ only, while lumbar injection 4% gel aluminum hydroxide 0.2ml sensitization.From sensitization second day, animal is divided into 2 groups at random: matched group, glutinous rehmannic stem and leaf crude extract (3) group, glutinous rehmannic stem and leaf crude extract (3) group glutinous rehmannic stem and leaf crude extract (3) 2.5g/kg gastric infusion, totally 14 days, behind the last medicine, animal is put in the airtight glass bell jar, after treating peace and quiet, start air compressor, spray into 30 seconds of 3.5% ovalbumin normal saline with the constant voltage of 53kPa (400mmHg), observe incubation period and the number of animals that takes place to twitch that the tic of panting property appears in Cavia porcellus in 6 minutes.(Xu Shuyun, Bian Rulian, Chen Xiu chief editor, pharmacological experimental methodology, the People's Health Publisher, in November, 1991 second edition, 1199 pages).
Table 4, glutinous rehmannic stem and leaf crude extract (3) are drawn the influence that Cavia porcellus breathes heavily to medicine
| Group | Number of animals n | Dosage (g/kg) | Draw and breathe heavily incubation period (second) | Tic number of animals n |
| Contrast glutinous rehmannic stem and leaf crude extract (3) | 10 10 | - 2.5 | 61.6±29.7 150.3±99.8 * | 10/10 9/10 |
Annotate: relatively think significant difference in P＜0.05 with the blank group, (with
*Expression).
Result of the test shows, glutinous rehmannic stem and leaf crude extract (3) 2.5g/kg dosage can draw the incubation period of breathing heavily Cavia porcellus by significant prolongation ovalbumin normal saline solution, compare with matched group that there were significant differences (P＜0.05), show that glutinous rehmannic stem and leaf crude extract (3) has certain antiasthmatic effect.
[embodiment five] get glutinous rehmannic stem and leaf 2kg, water 16000ml boils and extracted 1 hour, the leaching extracting solution, medicinal residues add water 12000ml again and boil extraction 1 hour, and leaching extracting solution, medicinal residues add water 12000ml again and boil extraction 1 hour, the leaching extracting solution, merge aqueous extract,, get glutinous rehmannic stem and leaf total heteroside 135g through further purification, HPLC, TLC detects and to show and contain catalpol (catalpol), glutinous rehmannic stem and leaf glycosides A, B, C, D (rehmannioside A, B, C, D), acetylcatalpol (acetylcatalpol), (dihydrocatalpol etc. also contain a spot of phenolic glycoside to the dihydro catalpol.Assay shows that catalpol content is 21.3%, and iridoid glycoside content is 51.4%.
The ovalbumin aerosol sucks to draw breathes heavily test
Get 60 of 200-250g Cavia porcelluss, male and female half and half, prior to right rear leg outside intramuscular injection 4% ovalbumin normal saline solution 0.2ml/ only, while lumbar injection 4% gel aluminum hydroxide 0.2ml sensitization.From sensitization second day, animal is divided into 2 groups at random: matched group, glutinous rehmannic stem and leaf total heteroside group, glutinous rehmannic stem and leaf total heteroside group glutinous rehmannic stem and leaf total heteroside 150mg/kg gastric infusion, totally 14 days, behind the last medicine, animal is put in the airtight glass bell jar, after treating peace and quiet, start air compressor, spray into 30 seconds of 3.5% ovalbumin normal saline, observe incubation period and the number of animals that tic takes place that the tic of panting property appears in Cavia porcellus in 6 minutes with the constant voltage of 53kPa (400mmHg).(chief editor such as Xu Shuyun, pharmacological experimental methodology, People's Health Publisher, second edition in 1991,1199 pages).
Table 5, glutinous rehmannic stem and leaf total heteroside draw the influence that Cavia porcellus breathes heavily to medicine
| Group | Number of animals (n) | Dosage (mg/kg) | Draw and breathe heavily incubation period (second) | Tic number of animals (only) |
| The contrast glutinous rehmannic stem and leaf total heteroside | 10 10 | - 150.0 | 57.8±31.3 145.5±97.4 * | 10/10 9/10 |
Annotate: relatively think significant difference in P＜0.05 with the blank group, (with
*Expression).
Result of the test shows, glutinous rehmannic stem and leaf glutinous rehmannic stem and leaf total heteroside 150mg/kg dosage can draw the incubation period of breathing heavily Cavia porcellus by significant prolongation ovalbumin normal saline solution, compare with matched group that there were significant differences (P＜0.05), show that the glutinous rehmannic stem and leaf glutinous rehmannic stem and leaf total heteroside has certain antiasthmatic effect.
Passive cutaneous anaphylaxis test (PCA)
The rat body is divided into 2 groups at random by heavy, 10/group, ♀ ♂ half and half, sub-cage rearing, 5/cage.Be respectively blank group, reagent group 150mg/kg.d.The glutinous rehmannic stem and leaf total heteroside of therapeutic administration is adopted in test, successive administration glutinous rehmannic stem and leaf total heteroside 14d before antigen is attacked.
Antiserum Preparation: with four sole injections of above-mentioned Radix Trichosanthis aluminium hydroxide suspension, every sole injection 0.1ml is total to the 0.4ml.10-15d maturation, and the about 10ml of eyeball blood-letting with the centrifugal 15min of 3000 commentaries on classics/min, gets upper serum and promptly gets antiserum.
Passive sensitization of skin: will test and respectively organize the rat back depilation, 2 points are respectively got apart from center line 1.5cm in the spinal column both sides, every some interval 2cm, the about 1 * 1cm2 of area, totally 4 points.In skin of back, inject sero-fast different dilution factors (1: 30 1: 40) respectively.Carrying out quantitative corresponding antigens behind the 48h attacks.The tail vein injection Radix Trichosanthis adds AZO-blue solution 1mg/kg, sacrificed by decapitation behind the 30min.
Observation index: the sero-fast local skin reaction of intradermal injection, and measure the locus coeruleus diameter that AZO-blue is oozed out.
Calculate PCA and suppress percentage rate (%).PCA suppresses percentage rate=(blank group locus coeruleus diameter-medication group locus coeruleus diameter)/blank group locus coeruleus diameter * 100% chief editors such as (, pharmacological experimental methodology, People's Health Publisher, second edition in 1991,1197 pages) Xu Shuyun.
Table 6, glutinous rehmannic stem and leaf total heteroside are to models of passive skin irritability of rats reaction influence
| Group n blank 1.47 ± 0.25 0.94 ± 0.20 *** | Number of animals 10 0.87 ± 0.26 0.60 ± 0.21 * | 1: 30 water glutinous rehmannic stem and leaf total heteroside of dosage mg/kg | Different serum-concentration locus coeruleus diameters (cm) 1: 40 | |
| 10 groups | 150.0 number of animals | |||
Annotate:
* *Compare P＜0.001 with the blank group,
*Compare P＜0.05 with the blank group
Result of the test sees Table 1.From table the result as can be seen, the reagent glutinous rehmannic stem and leaf total heteroside is antiserum dilution factor 1: 30,1: 40 o'clock, show significance and suppress locus coeruleus diameter (P＜0.05), suppression ratio is 36.1% and 31.0%.Show that reagent has certain inhibitory action to passive cutaneous anaphylaxis, PCA.
Tardy property footpad reaction test
Mice is pressed the body weight random packet, 10/group, ♀ ♂ half and half, sub-cage rearing, totally 2 groups, is respectively blank group, glutinous rehmannic stem and leaf total heteroside group by 5/cage.Adopt the therapeutic administration., administration 5d continues administration 5d before the sensitization to sensitization, altogether 10d.
0.05ml/ sensitization of NIH mice cervical region s.c5% sheep red blood cell (SRBC) (SRBC) behind the sensitization 5d.Right foot pad s.c5% sheep red blood cell (SRBC) 0.02ml attacks behind the 6d.Left side foot injection equivalent normal saline compares.Behind the 24h, last administration 50min puts to death animal.Cutting two foots from the ankle joint position weighs.Obtain the weight difference of two foots, calculate inhibitory rate of intumesce.Foot swelling suppression ratio=blank group foot swelling degree-medication group foot swelling degree)/and blank group foot swelling degree * 100%, result of the test sees Table 4.(chief editor such as Xu Shuyun, pharmacological experimental methodology, People's Health Publisher, second edition in 1991,1226 pages, 1228 pages)
The influence of the tardy property of the mice footpad reaction that table 7, glutinous rehmannic stem and leaf total heteroside cause sheep red blood cell (SRBC)
| Group | Number of animals (only) | Dosage (mg/kg) | Foot swelling degree (g) | Suppression ratio (%) |
| Blank group glutinous rehmannic stem and leaf total heteroside | 9 10 | Water 400.0 | 2.51±0.73 1.70±0.67 * | --- 32.3 |
Annotate: relatively think significant difference in P＜0.05 with the blank group, (with
*Expression).
From table the result as can be seen, glutinous rehmannic stem and leaf total heteroside and blank group comparison sheet reveal significance inhibition foot swelling degree (P＜0.05), suppression ratio is 32.3%.Show that glutinous rehmannic stem and leaf total heteroside is more obvious to the mice tardy property immunoreation effect that the inhibition sheep red blood cell (SRBC) causes.
[embodiment six] get glutinous rehmannic stem and leaf 30kg, water 240000ml boils and extracted 1 hour, the leaching extracting solution, medicinal residues add water 180000ml again and boil extraction 1 hour, and leaching extracting solution, medicinal residues add water 180000ml again and boil extraction 1 hour, the leaching extracting solution, merge aqueous extract,, get glutinous rehmannic stem and leaf total heteroside 2.12kg behind the vacuum drying through further purification, HPLC, TLC detects and to show and contain catalpol (catalpol), Martynoside. A, B, C, D (rehmannioside A, B, C, D), acetylcatalpol (acetylcatalpol), (dihydrocatalpol etc. also contain a spot of phenolic glycoside to the dihydro catalpol.Assay shows that catalpol content is 21.4%, and iridoid glycoside content is 51.5%.
The capsular preparation of glutinous rehmannic stem and leaf total heteroside, glutinous rehmannic stem and leaf total heteroside 1200 grams are sub-packed in 4000 capsules.Be glutinous rehmannic stem and leaf glycosides capsule preparation of the present invention.Specification is every and contains glutinous rehmannic stem and leaf total heteroside 300mg.
The clinical research of glutinous rehmannic stem and leaf total heteroside treatment asthma
1, case is selected 60 examples, male 30 examples, and women 30 examples, age 16-60 year, (People's Health Publisher, 1998, standard diagnostics p165) was the bronchial asthma patient according to chief editor'ss " asthma " such as Li Minghua.Be divided into 2 groups at random, every group 30 example, male 15 examples, women 15 examples; The A group is the treatment group, and B is a matched group.2, Therapeutic Method, treatment group glutinous rehmannic stem and leaf total heteroside capsule oral, each 1, was taken 30 days continuously at every day 3 times; The matched group propionic acid beclometasone aerosol, every day 2 times, each 200 μ g took 30 days continuously.3, therapeutic outcome, when treatment finished, the treatment group was cured 21 examples, effective 9 examples; Matched group is cured 12 examples, effective 18 examples.When treatment finished back 1 month, the treatment group was cured 15 examples, effective 13 examples; Matched group is cured 5 examples, effective 18 examples.
Claims (4)
1 glutinous rehmannic stem and leaf is in preparation treatment allergic asthma and/or the medicine of allergic rhinitis or the application of pharmaceutical composition.
2,, it is characterized in that glutinous rehmannic stem and leaf water extract, glutinous rehmannic stem and leaf 70% ethanol extraction or glutinous rehmannic stem and leaf methanolic extract are in preparation treatment allergic asthma and/or the medicine of allergic rhinitis or the application of pharmaceutical composition according to the application described in the claim 1.
3,, it is characterized in that the application of glutinous rehmannic stem and leaf, glutinous rehmannic stem and leaf water extract, glutinous rehmannic stem and leaf 70% ethanol extraction or glutinous rehmannic stem and leaf methanolic extract at preparation treatment allergic asthma medicine or pharmaceutical composition according to the application described in claim 1 or 2.
4,, it is characterized in that the application of glutinous rehmannic stem and leaf, glutinous rehmannic stem and leaf water extract, glutinous rehmannic stem and leaf 70% ethanol extraction or glutinous rehmannic stem and leaf methanolic extract at preparation treatment of allergic rhinitis medicine or pharmaceutical composition according to the application described in claim 1 or 2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100622468A CN100349590C (en) | 2004-07-02 | 2004-07-02 | Medicinal use of glutinous rehmannia stem and leaf and its extract for preventing asthma and anti-allergy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100622468A CN100349590C (en) | 2004-07-02 | 2004-07-02 | Medicinal use of glutinous rehmannia stem and leaf and its extract for preventing asthma and anti-allergy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1714841A CN1714841A (en) | 2006-01-04 |
| CN100349590C true CN100349590C (en) | 2007-11-21 |
Family
ID=35821202
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100622468A Expired - Fee Related CN100349590C (en) | 2004-07-02 | 2004-07-02 | Medicinal use of glutinous rehmannia stem and leaf and its extract for preventing asthma and anti-allergy |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100349590C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1947757B (en) * | 2006-09-16 | 2010-05-12 | 四川美大康药业股份有限公司 | Leave of glutinous rehmannia extractive, its preparation method and use, medicines prepared with said extractives |
| KR101476095B1 (en) * | 2013-04-10 | 2014-12-23 | 영진약품공업주식회사 | a purified extract isolated from Pseudolysimachion rotundum var. subintegrum containing abundunt amount of catapol derivatives, as an active ingredient for preventing or treating chronic obstructive pulmonary disease |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1061780A (en) * | 1990-12-01 | 1992-06-10 | 卢存寿 | The extraction process of the excited new drug rehmannioside of prepituitary gland |
-
2004
- 2004-07-02 CN CNB2004100622468A patent/CN100349590C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1061780A (en) * | 1990-12-01 | 1992-06-10 | 卢存寿 | The extraction process of the excited new drug rehmannioside of prepituitary gland |
Non-Patent Citations (1)
| Title |
|---|
| 变态反应性皮肤病的中医药治疗 张筑麟.贵阳中医学院学报，第14卷第1期 1992 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1714841A (en) | 2006-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101062289A (en) | External application medicine combination for treating gout | |
| CN103768308A (en) | Medicament composition for treating upper respiratory infections and preparation method thereof | |
| CN1267113C (en) | Extract of mulberry twig and its extracting process and novel usage | |
| CN1179729C (en) | Pharmaceutical composition having antitumor activity and process for the preparation thereof | |
| CN1806821A (en) | Rhinitis-treating medicine | |
| CN115337356A (en) | Pharmaceutical composition for treating rheumatoid arthritis and preparation method thereof | |
| WO2004054596A1 (en) | A medicament containing epidemium extract for treatment of prostatic hyperplasia and prostatitis | |
| CN100349590C (en) | Medicinal use of glutinous rehmannia stem and leaf and its extract for preventing asthma and anti-allergy | |
| CN114404462B (en) | Composition and application thereof in preparation of medicine for treating gastric injury and/or gastric ulcer | |
| CN100349589C (en) | Medical application of rehmannia root extractive in resisting asthma and allergy | |
| CN1698841A (en) | Medical usage of picrorhiza rhizome total glycoside extract | |
| CN1332675C (en) | Medicine application of catalpa and extractive for anti allergic disease | |
| CN1468601A (en) | Picroside-II as one new medicine for preventing and treating allergic and inflammatory diseases | |
| CN1278709C (en) | Medicine for treating cold and its preparing process | |
| CN104998034A (en) | Chinese herbal medicine combination drug treating livestock respiratory diseases and preparation method thereof | |
| Mali et al. | Wound healing activity of Calotropis procera root bark on diabetic rats | |
| CN101015622A (en) | Medicinal use of radix rehmanniae total glucosides extractive and preparing method thereof | |
| CN1248709C (en) | Chinese medicine prepn for stopping drug addiction | |
| CN106188083B (en) | A method of extracting 1, 8-Cineole volatile oil from folium artemisiae argyi | |
| CN103223058B (en) | Fructus Viticis Negundo total flavone extract, and preparation method and medicinal uses thereof | |
| CN111840494B (en) | Anti-gout traditional Chinese medicine composition, preparation method and application thereof | |
| Ahirwar et al. | Antihistaminic effect of Sitopaladi churna extract | |
| CN100341532C (en) | External use preparation for treating bliser tetter | |
| CN1105564C (en) | Medicine for warming kidney and treating wind-dampness syndrome and preparation process thereof | |
| CN107375409B (en) | Application of bauhinia championii polymethoxyl total flavonoids in treatment and prevention of gastric ulcer |
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 | ||
| ASS | Succession or assignment of patent right |
Owner name: BEIJING TIANJIAO AOTEQI CHINESE-MONGOLIAN TRADITIO Free format text: FORMER OWNER: LUO HESHENG Effective date: 20100108 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20100108 Address after: Floor 1, No. 5-1 East Road, Beijing, Haidian District Patentee after: Beijing Tianqiao Aoteqi Chinese and Mongolian Medicines Engineering Technology Research Co., Ltd. Address before: Beijing, Changping, Shahe Exhibition Road No. 27 Patentee before: Luo Hesheng |
|
| ASS | Succession or assignment of patent right |
Owner name: INNER MONGOLIA OTAQI MONGOLIAN MEDICINE CO., LTD. |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20110520 Address after: 100085, No. 5-1 East Road, Beijing, Haidian District Co-patentee after: Inner Mongolia Otaqi Mongolian Medicine Co., Ltd. Patentee after: Beijing Tianqiao Aoteqi Chinese and Mongolian Medicines Engineering Technology Research Co., Ltd. Address before: 100085, No. 5-1 East Road, Beijing, Haidian District Patentee before: Beijing Tianqiao Aoteqi Chinese and Mongolian Medicines Engineering Technology Research Co., Ltd. |
|
| DD01 | Delivery of document by public notice |
Addressee: Wang Cuixia Document name: Notification to Pay the Fees |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20071121 Termination date: 20200702 |