CN115137803B - 一种治疗围绝经期抑郁症的中药组合物及其制备方法与应用 - Google Patents
一种治疗围绝经期抑郁症的中药组合物及其制备方法与应用 Download PDFInfo
- Publication number
- CN115137803B CN115137803B CN202210815024.7A CN202210815024A CN115137803B CN 115137803 B CN115137803 B CN 115137803B CN 202210815024 A CN202210815024 A CN 202210815024A CN 115137803 B CN115137803 B CN 115137803B
- Authority
- CN
- China
- Prior art keywords
- depression
- group
- traditional chinese
- chinese medicine
- rats
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 35
- 239000000203 mixture Substances 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000002994 raw material Substances 0.000 claims abstract description 13
- 240000005373 Panax quinquefolius Species 0.000 claims abstract description 10
- 235000003140 Panax quinquefolius Nutrition 0.000 claims abstract description 10
- 244000303040 Glycyrrhiza glabra Species 0.000 claims abstract description 8
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims abstract description 8
- 244000246386 Mentha pulegium Species 0.000 claims abstract description 8
- 235000016257 Mentha pulegium Nutrition 0.000 claims abstract description 8
- 235000004357 Mentha x piperita Nutrition 0.000 claims abstract description 8
- 244000197580 Poria cocos Species 0.000 claims abstract description 8
- 235000008599 Poria cocos Nutrition 0.000 claims abstract description 8
- 244000273928 Zingiber officinale Species 0.000 claims abstract description 8
- 235000006886 Zingiber officinale Nutrition 0.000 claims abstract description 8
- 244000126002 Ziziphus vulgaris Species 0.000 claims abstract description 8
- 235000008397 ginger Nutrition 0.000 claims abstract description 8
- 235000001050 hortel pimenta Nutrition 0.000 claims abstract description 8
- 241000132012 Atractylodes Species 0.000 claims abstract description 7
- 235000006533 astragalus Nutrition 0.000 claims abstract description 7
- 241000382455 Angelica sinensis Species 0.000 claims abstract description 6
- 235000017443 Hedysarum boreale Nutrition 0.000 claims abstract description 6
- 235000007858 Hedysarum occidentale Nutrition 0.000 claims abstract description 6
- 240000006079 Schisandra chinensis Species 0.000 claims abstract description 6
- 235000021307 Triticum Nutrition 0.000 claims abstract description 6
- 239000001947 glycyrrhiza glabra rhizome/root Substances 0.000 claims abstract description 6
- 241000045403 Astragalus propinquus Species 0.000 claims abstract description 5
- 240000002948 Ophiopogon intermedius Species 0.000 claims abstract description 5
- 244000236658 Paeonia lactiflora Species 0.000 claims abstract description 5
- 235000008598 Paeonia lactiflora Nutrition 0.000 claims abstract description 5
- 235000008422 Schisandra chinensis Nutrition 0.000 claims abstract description 4
- 244000098338 Triticum aestivum Species 0.000 claims abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 14
- 239000000706 filtrate Substances 0.000 claims description 11
- 239000000843 powder Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- 241000202726 Bupleurum Species 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- 239000012153 distilled water Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 2
- 238000000227 grinding Methods 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 241000700159 Rattus Species 0.000 abstract description 87
- 230000000694 effects Effects 0.000 abstract description 40
- 229940088597 hormone Drugs 0.000 abstract description 8
- 239000005556 hormone Substances 0.000 abstract description 8
- 230000033228 biological regulation Effects 0.000 abstract description 5
- 230000007267 depressive like behavior Effects 0.000 abstract description 3
- 230000002314 neuroinflammatory effect Effects 0.000 abstract description 3
- 230000000994 depressogenic effect Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 37
- 210000004185 liver Anatomy 0.000 description 35
- 210000000952 spleen Anatomy 0.000 description 22
- 230000006870 function Effects 0.000 description 21
- 210000002216 heart Anatomy 0.000 description 18
- 230000001965 increasing effect Effects 0.000 description 18
- 230000001502 supplementing effect Effects 0.000 description 18
- 210000002966 serum Anatomy 0.000 description 14
- 239000010029 xiaoyaosan Substances 0.000 description 14
- 210000004072 lung Anatomy 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 229940011871 estrogen Drugs 0.000 description 11
- 239000000262 estrogen Substances 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- 230000008901 benefit Effects 0.000 description 10
- 210000002784 stomach Anatomy 0.000 description 10
- 230000037406 food intake Effects 0.000 description 9
- 210000003734 kidney Anatomy 0.000 description 9
- 230000001737 promoting effect Effects 0.000 description 9
- 235000019640 taste Nutrition 0.000 description 9
- 102000009151 Luteinizing Hormone Human genes 0.000 description 8
- 108010073521 Luteinizing Hormone Proteins 0.000 description 8
- 235000009508 confectionery Nutrition 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 230000012173 estrus Effects 0.000 description 8
- 229940040129 luteinizing hormone Drugs 0.000 description 8
- 230000004938 stress stimulation Effects 0.000 description 8
- 238000001356 surgical procedure Methods 0.000 description 8
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 7
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 229940028334 follicle stimulating hormone Drugs 0.000 description 7
- 210000001061 forehead Anatomy 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 102000003810 Interleukin-18 Human genes 0.000 description 6
- 108090000171 Interleukin-18 Proteins 0.000 description 6
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 102000000874 Pyrin Domain-Containing 3 Protein NLR Family Human genes 0.000 description 6
- 108010001946 Pyrin Domain-Containing 3 Protein NLR Family Proteins 0.000 description 6
- 235000012631 food intake Nutrition 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 235000019605 sweet taste sensations Nutrition 0.000 description 6
- 102000003777 Interleukin-1 beta Human genes 0.000 description 5
- 108090000193 Interleukin-1 beta Proteins 0.000 description 5
- 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 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 210000000582 semen Anatomy 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 230000035900 sweating Effects 0.000 description 5
- 230000002936 tranquilizing effect Effects 0.000 description 5
- 210000004291 uterus Anatomy 0.000 description 5
- 241000209140 Triticum Species 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 4
- 210000002510 keratinocyte Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000008539 xiaoyao Substances 0.000 description 4
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- 206010011224 Cough Diseases 0.000 description 3
- 235000006679 Mentha X verticillata Nutrition 0.000 description 3
- 235000002899 Mentha suaveolens Nutrition 0.000 description 3
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 3
- 241001619461 Poria <basidiomycete fungus> Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000006978 adaptation Effects 0.000 description 3
- 210000000577 adipose tissue Anatomy 0.000 description 3
- 230000001914 calming effect Effects 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 230000035622 drinking Effects 0.000 description 3
- 229960005309 estradiol Drugs 0.000 description 3
- 229930182833 estradiol Natural products 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 210000004243 sweat Anatomy 0.000 description 3
- 230000009182 swimming Effects 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 238000012549 training Methods 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- 241001061264 Astragalus Species 0.000 description 2
- 235000006484 Paeonia officinalis Nutrition 0.000 description 2
- 241001106477 Paeoniaceae Species 0.000 description 2
- 208000004880 Polyuria Diseases 0.000 description 2
- 208000001431 Psychomotor Agitation Diseases 0.000 description 2
- 206010038743 Restlessness Diseases 0.000 description 2
- 206010039424 Salivary hypersecretion Diseases 0.000 description 2
- 241000555745 Sciuridae Species 0.000 description 2
- 235000006545 Ziziphus mauritiana Nutrition 0.000 description 2
- 240000008866 Ziziphus nummularia Species 0.000 description 2
- 235000008529 Ziziphus vulgaris Nutrition 0.000 description 2
- 230000006578 abscission Effects 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 235000019658 bitter taste Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000003679 cervix uteri Anatomy 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000035619 diuresis Effects 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 102000015694 estrogen receptors Human genes 0.000 description 2
- 108010038795 estrogen receptors Proteins 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 210000000232 gallbladder Anatomy 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 208000024714 major depressive disease Diseases 0.000 description 2
- 230000005906 menstruation Effects 0.000 description 2
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000009806 oophorectomy Methods 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000002360 prefrontal effect Effects 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 208000026451 salivation Diseases 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 238000005728 strengthening Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000004233 talus Anatomy 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 101150084750 1 gene Proteins 0.000 description 1
- 206010000234 Abortion spontaneous Diseases 0.000 description 1
- 206010048998 Acute phase reaction Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 244000061520 Angelica archangelica Species 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 244000236521 Bupleurum rotundifolium Species 0.000 description 1
- 235000015221 Bupleurum rotundifolium Nutrition 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010012374 Depressed mood Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 206010054089 Depressive symptom Diseases 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000021663 Female sexual arousal disease Diseases 0.000 description 1
- 108700012941 GNRH1 Proteins 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 235000001287 Guettarda speciosa Nutrition 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 206010067371 Menopausal depression Diseases 0.000 description 1
- 235000004049 Mentha X gracilis Nutrition 0.000 description 1
- 244000155567 Mentha x cardiaca Species 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 240000003243 Thuja occidentalis Species 0.000 description 1
- 235000008109 Thuja occidentalis Nutrition 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004658 acute-phase response Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000011281 clinical therapy Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007357 depressive behavior Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000006397 emotional response Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000009164 estrogen replacement therapy Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 210000003195 fascia Anatomy 0.000 description 1
- 238000009093 first-line therapy Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 101150108262 gnrh1 gene Proteins 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 230000004185 hypothalamic-pituitary-gonadal axis Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 235000011477 liquorice Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 230000001592 luteinising effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 238000004377 microelectronic Methods 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 208000015994 miscarriage Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003959 neuroinflammation Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 208000033300 perinatal asphyxia Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 230000008288 physiological mechanism Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000007425 progressive decline Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000031877 prophase Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000005982 spleen dysfunction Effects 0.000 description 1
- 208000000995 spontaneous abortion Diseases 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
-
- 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
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
- A61K36/076—Poria
-
- 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
- A61K36/13—Coniferophyta (gymnosperms)
- A61K36/14—Cupressaceae (Cypress family), e.g. juniper or cypress
-
- 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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/233—Bupleurum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/284—Atractylodes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/534—Mentha (mint)
-
- 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)
- A61K36/57—Magnoliaceae (Magnolia family)
-
- 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)
- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
-
- 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)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
-
- 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)
- A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
- A61K36/725—Ziziphus, e.g. jujube
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8968—Ophiopogon (Lilyturf)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9068—Zingiber, e.g. garden ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明公开了一种中药组合物,由以下重量配比的原料制备而成:当归15g、白芍15g、柴胡10g、茯苓15g、白术15g、炙甘草10g、生姜5g、薄荷5g、黄芪15g、西洋参10g、小麦30g、大枣5g、酸枣仁15g、柏子仁15g、麦冬15g以及五味子10g。本发明中药组方针对围绝经期抑郁症大鼠的抑郁样行为、各项激素水平、神经炎症因子等均具有较好的调节作用。
Description
技术领域
本发明涉及一种中药组合物,用于治疗围绝经期抑郁症,属于中药研究技术领域。
背景技术
围绝经期抑郁症(Perimenopausal Depression,PMD)又称为更年期抑郁症,是一种情绪障碍,是指女性在进入绝经期前后因出现生殖机能减弱,卵巢功能由旺盛走向衰退,性激素逐渐缺乏,从而导致的以情绪低落和焦虑不安为主要症状的一类精神性疾病。PMD常发生于45~55岁,表现为烦躁、焦虑、内心不安、甚至惊慌恐惧,记忆力减退、缺乏自信、行动迟缓,严重者对外界冷淡,丧失情绪反应,甚至发展成严重的抑郁性神经官能症。围绝经期抑郁症与女性体内的雌激素含量下降甚为密切,外界环境刺激(如家庭生活、工作压力、社会角色变化等)及体内雌激素水平下降被认为是PMD发病的内、外两个主要因素(Zhao Y,Munro-Kramer ML,Shi S,et al.A longitudinal study of perinatal depressionamong Chinese high-risk pregnant women[J].Women Birth,2018,31(6):e395-e402)。大量研究证实,雌激素具有神经保护及调节作用,雌激素水平的异常波动与抑郁症呈现极高的相关性,围绝经期女性雌激素水平的急剧下降是诱发抑郁症的原因之一。有研究表明,女性患抑郁症的几率是男性的2倍(Karaoulanis SE,Rizouli KA,Rizoulis AA,etal.Lack of associ-ation of acute phase response proteins with hormone levelsand antidepressant medication in perimenopausal depression[J].BMC Psychiatry,2014,14(6):164-169),且女性在围绝经期更易患抑郁症。数据显示,近1/3的围绝经期女性可出现显著的抑郁症状。围绝经期时间越长,抑郁症的发生的比例越高(Jagtap BL,PrasadBS,Chaudhury S.Psychiatric morbidity in perimenopausal women[J].IndPsychiatry J,2016,25(1):86-92)。PMD严重危害女性的身心健康,影响日常生活和工作,给家庭和社会造成负担,已日益受到妇科、精神科等领域的重视。
围绝经期期间,妇女会受到卵巢激素不稳定波动,由于雌激素的减退使下丘脑-垂体-性腺轴(Hypothalamic-pituitary-ovary,HPO)被正反馈激活,促性腺激素释放激素(Gonadotropin-releasing hormone,GnRH)、促卵泡生成激素(Follicle-stimulatingHormone,FSH)、黄体生成素(Luteinising Hormone,LH)的释放和生成得到增强。由于雌二醇(Estradiol,E2)的缺乏,对大脑海马的雌激素受体ERα、ERβ的刺激减少,这被认为是围绝经期女性常常陷入抑郁、焦虑等精神障碍中的生理机制之一(Ozsoy Filiz,Nursal AyseFeyda,Karakus Nevin,Demir Meral Oran,Yigit Serbulent.Estrogen Receptor 1Geners22346939and rs9340799Variants are associated with Major Depressive Disorderand its Clinical Features.[J].Current neurovascular research,2021.;Hwang WuJeong,Lee Tae Young,Kim Nahrie Suk,Kwon Jun Soo.The Role of EstrogenReceptors and Their Signaling across Psychiatric Disorders[J].InternationalJournal of Molecular Sciences,2020,22(1).)。因此,雌激素戒断被认为是引发围绝经期抑郁症状的主要因素,雌激素/激素替代疗法已被认为是PMD治疗的一线临床疗法(StuddJ.HRT should be considered as first line therapy for perimenopausaldepression:FOR:Estrogens are the first line treatment for perimenopausalwomen[J].BJOG,2016,123(6):1011.;Dwyer J B,Aftab A,Radhakrishnan R,etal.Hormonal Treatments for Major DepressiveDisorder:State of the Art[J].Am JPsychiatry,2020,177(8):686-705.)。虽然雌激素补充疗法在临床上有着应用广泛、可操作性强、疗效确切等优势,但是长期服用雌激素所带来的其他并发症也不容忽视,可能会增加乳腺癌和卵巢癌,中风和心血管疾病的风险(Rubinow D R,Johnson S L,Schmidt P J,et al.EFFICACY OF ESTRADIOL INPERIMENOPAUSAL DEPRESSION:SO MUCH PROMISE ANDSO FEW ANSWERS[J].Depress Anxiety,2015,32(8):539-549.)。因此探寻副作用小、作用靶点多、具有整体调节作用的中药复方制剂就显得尤为重要,这将是中医药治疗围绝经期抑郁症的发展方向。
发明内容
本发明的目的是提供一种具有整体调节作用、能够有效治疗围绝经期抑郁症的中药组合物。
本发明提供的中药组合物由以下重量配比的原料制备而成:当归15g、白芍15g、柴胡10g、茯苓15g、白术15g、炙甘草10g、生姜5g、薄荷5g、黄芪15g、西洋参10g、小麦30g、大枣5g、酸枣仁15g、柏子仁15g、麦冬15g以及五味子10g。
本发明中药组合物中包括16种药材,其中,当归、白芍、柴胡、茯苓、白术、炙甘草、生姜、薄荷选自传统古方逍遥散:当归(Angelicasinensis),味甘、性温,归肝经、心经、脾经,具有补血活血、调经止痛、润燥滑肠之功效;白芍(Radix paeoniae alba),又称青羊参味甘、辛,性温,归肝经、脾经、肾经,具有养血调经、敛阴止汗、柔肝止痛、平抑肝阳之功效;柴胡(Radix bupleuri),味苦、辛,性微寒,归肝经、胆经,具有疏肝利胆、疏气解郁、散火之功效;茯苓(Poria cocos),味甘、性平,归心经、肺经、脾经,具有渗湿利水、健脾和胃、宁心安神之功效;白术(Rhizoma Atractylodis Macrocephalae),味苦、甘、性温,归脾经、胃经,具有健脾益气、燥湿利水、止汗、安胎之功效;甘草(liquorice),味甘、性平,归心经、肺经、脾经、胃经,具有补脾益气、清热解毒、祛痰止咳、调和药性之功效。生姜(fresh ginger),味辛、性微温,归肺经、脾经、胃经,具有发汗解表,温中止呕,温肺止咳之功效;薄荷(mint),味辛、性凉,归肺经和肝经,具有发散风热、清利头目、利咽、透疹之功效;并在此基础上增加:黄芪(Astragalus membranaceus),味甘、性微温,归肺经、脾经、肝经、肾经,具有补气、止汗、利尿消肿、排脓之功效;西洋参(American ginseng),又称花旗参,味甘、性寒,归心经、肺经、肾经,具有补气益胃、养阴、清火之功效;小麦(wheat),味甘、性凉,归心经、脾经、肾经,具有养心安神、除烦之功效;大枣(Chinese-date),味甘、性温,归脾经、胃经,具有补脾和营,补中益气之功效;酸枣仁(spina date seed),性甘、味平,归心经、脾经、肝经、胆经,具有养肝,宁心,安神,敛汗之功效;柏子仁(semen boitae),味甘、性平,归心经、肾经、大肠经,具有养心安神、润肠通便之功效;麦冬(Radix Ophiopogonis),味甘、微苦、性微寒,归心肺、胃经,具有养阴生津、润肺止咳之功效;五味子(Schisandra chinensis),味甘、性温,归肺经、心经、肾经,具有滋肾、敛肺、收汗、生津之功效。
本方为肝郁血虚,脾失健运之证而设。既有柴胡疏肝解郁,又有当归、白芍养血柔肝。尤其当归之芳香可以行气,味甘可以缓急,更是肝郁血虚之要药。白术、茯苓健脾去湿,使运化有权,气血有源。炙甘草益气补中,缓肝之急,虽为佐使之品,却有襄赞之功。生姜烧过,温胃和中之力益专,薄荷少许,助柴胡疏肝郁而生之热。柴胡的疏肝解郁,以顺肝性;当归、白芍的养肝血,柔肝体,帮助柴胡恢复肝正常的顺达之性;白术、茯苓的益气健脾,促进气血生化;甘草配合茯苓、白术以益气健脾,配白芍以缓急止痛;薄荷的辛凉,助柴胡以疏肝气、解郁热;生姜辛温,助柴胡、薄荷疏肝,助茯苓、白术以健脾胃。西洋参的补气益胃功效,养心安神、除烦功效;大枣的补脾和营,补中益气功效;酸枣仁的养肝,宁心安神,敛汗功效;柏子仁的养心安神功效;麦冬的养阴生津功效;五味子的滋肾敛肺功效,诸药相配,体现了肝脾同治,益气养心,重在治肝之法。
本发明还提供了上述中药组合物的制备方法:
(1)按照重量配比称取各原料药,将各原料药混合均匀,加入原料药总重量10倍的蒸馏水,浸泡1小时后,再煎煮1小时,冷却;
(2)将步骤(1)冷却后的药液用纱布过滤,得到第一次滤液;
(3)取步骤(2)过滤后的药物残渣,重复步骤(1)和(2)得到第二次滤液,合并二次滤液;
(4)将步骤(3)中合并的二次滤液,干燥,得干膏;
(5)将得到的干膏粉碎、研磨,即得干粉状的所述中药组合物。
本发明还提供了上述中药组合物在制备治疗围绝经期抑郁症药物上的应用。
本发明相比现有技术具有以下优点:
1、本发明在传统经典方逍遥散的基础上,以薄荷助柴胡以疏肝气、解郁热;以生姜助柴胡、薄荷疏肝,助茯苓、白术以健脾胃;辅以黄芪补气、止汗排脓之功效,西洋参补气养心之功效,小麦养心安神之功效,并辅以大枣的补脾合营之功效,酸枣仁的养肝、宁心、敛汗之功效,同时结合柏子仁的养心安神功效、麦冬的养阴生津功效、五味子的滋肾敛肺功效,诸药相配,在重在治肝之法同时,以肝脾同治,对肝、脾、肾等进行整体调和。
2、本发明中药组方,在现代药理研究中发现,针对围绝经期抑郁症大鼠的抑郁样行为、各项激素水平、神经炎症因子等均具有较好的调节作用,且优于逍遥散。
3、本发明以中药复合制剂进行围绝经期抑郁症的治疗,副作用小、作用靶点多、具有整体调节作用,也是在对古方改进上的一个重大突破。
附图说明
图1为正常大鼠动情周期HE染色图。
具体实施方式
下面结合具体实施例对本发明进行详细说明。
实施例1
本发明中药组合物的原料药重量配比:
当归3份、白芍3份、柴胡2份、茯苓3份、白术3份、炙甘草2份、生姜1份、薄荷1份、黄芪3份、西洋参2份、小麦6份、大枣1份、酸枣仁3份、柏子仁3份、麦冬3份以及五味子2份。
制备过程方法如下:
(1)按照所述的重量份称取各原料药,将各原料药混合均匀后加入药物重量10倍的蒸馏水,浸泡1小时后,煎煮1小时,冷却;
(2)将步骤(1)冷却后的药液用纱布过滤,得到第一次滤液;
(3)取步骤(2)剩余的药物残渣,重复步骤(1)和(2)得到第二次滤液,合并二次滤液;
(4)设定电热恒温鼓风干燥箱温度为70℃,干燥5d,得到所述中药组合物的干膏。
(5)将得到的干膏放在粉碎机内粉碎,研磨,过滤,即为本发明中药组合物的干粉,命名为益气排郁复方。
实施例2
药效评价
本实验中所得数据采用SPSS 17.0软件进行统计学处理分析。以均数±标准差表示。
一、围绝经期抑郁症模型大鼠的制备及评价
1.1围绝经期大鼠模型制备
采用双侧卵巢摘除术(ovariectomy,OVX)制备围绝经期大鼠模型。具体操作方法为:用0.3%戊巴比妥腹部注射(0.15ml/100g)将大鼠麻醉后备皮大鼠背部最下肋缘至骶尾部皮肤,用碘伏充分消毒后纵向剪开距脊柱两旁约1.5cm,最下肋缘1cm皮肤,创口长径约2cm。逐层剪开皮肤、筋膜,并钝性分离肌肉暴露腹腔内脂肪组织,拉出脂肪组织后在其中找到大鼠卵巢,沿子宫颈远端充分结扎止血后摘除卵巢。确认无活动性出血后还纳其余组织,逐层缝合创口并用碘伏充分消毒,清洁敷料包扎创口。按20万U/只剂量肌注青霉素以预防感染。术后将大鼠放置于单笼饲养,清洁垫料,禁食禁水24h,密切观察大鼠状态。术后待大鼠恢复9日,第10日起连续5天,用一次性采样管吸取0.5ml生理盐水冲吸大鼠阴道脱落细胞并制备涂片,HE染色后观察大鼠动情周期并记录,若无规律动情周期出现则可视为造模成功。
1.2孤养法复合慢性不可预知温和应激(CUMS)模型的建立
对制备完成的OVX模型大鼠采用单笼饲养至取材结束。手术恢复活动第8天,所有模型动物均进行28d CUMS处理,每天日、夜间各给予一种应激方法对大鼠进行刺激,应激方法顺序按照随机数字表分布,周内不重复,使大鼠无法预测刺激出现的规律,同时避免产生应激耐受作用(详见表1)。
表1 CUMS日程表
a电击;b光照;c拥挤;d禁食;e夹尾;f禁水;g束缚;h潮湿垫料:i摇晃笼子;j悬尾;k冰水游泳;l闪光;m气味刺激;n倾斜笼子。
二、动物分组及给药方法
将60只围绝经期抑郁症(PMD)模型复制成功的大鼠随机分为6组,每组10只,雌雄各半,分别为模型组、益气排郁复方(即本发明实施例1中制备得到的中药组合物)高剂量组(生药量11.6g/kg)、益气排郁复方中剂量组(生药量5.8g/kg)、益气排郁复方低剂量组(生药量2.9g/kg)、阳性对照组1(舒肝解郁胶囊0.13g/kg)和阳性对照组2(逍遥散0.95g/kg),给药组动物按体重灌胃给药,1次/d,连续给药28天,灌胃容积为10mL/kg,模型组给予同容积的生理盐水,另取10只预处理动物为假手术组。除假手术组以外,其余各组动物均进行28d CUMS模型制作。应激造模期间伴随动物给药,每天上午8点给药,1.5h后进行日间应激处理,19点进行夜间应激处理。
三、观察指标及检测
3.1围绝经期抑郁症模型大鼠体质量和摄食量测定
于给药前、给药后每周测定并记录所有大鼠体质量和摄食量,分析本发明益气排郁复方各剂量组以及其它各处理组对各组大鼠体重变化和饮食的影响。
表2 益气排郁复方对PMD模型大鼠体重的影响(n=10)
注:与假手术组比较,▲▲P<0.01;与模型组比较,*P<0.05,**P<0.01;与逍遥散组比较,#P<0.05,##P<0.01.
表2结果显示,应激刺激前各组大鼠平均体重相近,差异无显著性意义(P>0.05)。应激刺激第1周末至第4周末模型组与假手术组比较,大鼠体重均明显降低,差异具有显著性意义(P<0.01);应激刺激第2周末益气排郁复方高剂量组与模型组比较,体重增加,差异具有显著性意义(P<0.05);应激刺激第3周末益气排郁复方中剂量组与模型组比较,体重增加,差异具有显著性意义(P<0.05);应激刺激第4周末益气排郁复方高、中、低剂量组、舒肝解郁胶囊组、逍遥散组与模型组比较,体重均明显增加,差异具有显著性意义(P<0.05,P<0.01);益气排郁复方中剂量组与逍遥散组比较,体重明显增加,差异具有显著性意义(P<0.01)。
表3 益气排郁复方对PMD模型大鼠摄食量的影响(n=10)
注:与假手术组比较,▲▲P<0.01;与模型组比较,*P<0.05,**P<0.01;与逍遥散组比较,#P<0.05.
表3结果显示,应激刺激前各组大鼠摄食量相近,差异无显著性意义(P>0.05)。应激刺激第1周末至第4周末模型组与假手术组比较,大鼠摄食量均明显降低,差异具有显著性意义(P<0.05,P<0.01);应激刺激第3周末至第4周末益气排郁复方高、中剂量组与模型组比较,摄食量均明显增加,差异具有显著性意义(P<0.05);应激刺激第4周末舒肝解郁胶囊与模型组比较,摄食量均明显增加,差异具有显著性意义(P<0.05);应激刺激第3周末益气排郁复方中剂量组与逍遥散组比较,摄食量明显增加,差异具有显著性意义(P<0.05)。
3.2大鼠阴道脱落细胞HE染色
在双侧卵巢摘除术后待大鼠自然恢复7日,再进行阴道脱落细胞采集,连续5天每天上午10:00开始采集,使用1ml一次性胶头滴管吸取生理盐水0.5ml对大鼠阴道内冲吸3次,将吸取液均匀滴在玻片上,做HE染色后在光镜下观察并依据相关文献判断并记录动情周期。在末次给药前5天,再次采集大鼠阴道脱落细胞涂片并做HE染色,在光镜下进行观察后并记录入结果。
如图1HE染色结果显示:
A动情前期:以有核上皮细胞(蓝色↑)为主,伴有少量上皮角化细胞。
B动情期:以落叶状堆积的无核角化细胞(黑色↑)为主。
C动情后期:白细胞(黄色↑)、有核上皮细胞、角化细胞同时出现。
D动情间期:视野内见大量白细胞,偶见角化细胞。
3.3抑郁行为评价
3.3.1蔗糖饮水偏好实验
蔗糖饮水偏好实验分为3个部分,包括适应训练、基础糖水/纯水消耗实验和糖水偏好实验检测。在制作OVX模型前进行适应训练,在每只鼠笼上放两瓶1%的蔗糖水。适应24h后,每只鼠笼上放入1瓶1%的蔗糖水和1瓶普通纯水,饮用一日。禁食禁水24h后,进行基础糖水/纯水消耗实验检测,将大鼠单笼饲养,给予每只大鼠定量的两瓶水:1%的蔗糖水和普通纯水。观察24h内每只大鼠的糖水消耗量和纯水消耗量,取材前进行糖水偏好实验检测,方法与基础糖水/纯水消耗实验操作一致。糖水偏好指数=糖水消耗量/(糖水消耗量+纯水消耗量)×100%。检测24小时内大鼠糖水偏好指数。
3.3.2强迫游泳实验
准备高50cm直径20cm圆柱形透明容器,加水深15cm,控制水温至室温(23~25℃)。提前24h以上进行大鼠适应性训练,将大鼠分别置于水中计时15min,取出后吹干大鼠并放归原饲养环境。次日进行正式实验,将大鼠至于水中并计时6min,记录后4min内大鼠进入绝望状态(相对静止)时间,每只鼠之间需更换清水以避免前者效应。强迫游泳实验时大鼠绝望状态判断依据:1.探索活动停止;
2.四肢活动停止或减少;3.双目微闭。当满足1时,满足条件2或3则认为大鼠进入绝望状态。
3.3.3悬尾实验
准备离地高50cm支架,将大鼠尾根部用细绳固定并悬挂于支架上,悬挂时大鼠头部距离地面15cm为佳。计时6min,计算后4分钟内大鼠进入绝望状态(相对静止)时间。悬尾实验时大鼠绝望状态判断依据:1.探索性活动停止;2.四肢活动停止;3.双目微闭。当满足条件1时,满足条件2或3则认为大鼠进入绝望状态。
3.3.4结果
表4 益气排郁复方对PMD模型大鼠抑郁行为学作用的影响
注:与假手术组比较,▲▲P<0.01;与模型组比较,*P<0.05,**P<0.01;与逍遥散组比较,#P<0.05,##P<0.01.
表4结果显示,治疗4周后,模型组与假手术组比较,大鼠糖水偏好指数明显降低,差异具有显著性意义(P<0.01)。益气排郁复方高、中剂量组和舒肝解郁胶囊组与模型组比较,大鼠糖水偏好指数均明显升高,差异具有显著性意义(P<0.05,P<0.01);益气排郁复方中、低剂量组与逍遥散组比较,大鼠糖水偏好指数均明显升高,差异具有显著性意义(P<0.05)。
模型组与假手术组比较,大鼠累计不动总时间明显升高,差异具有显著性意义(P<0.01)。益气排郁复方高、中剂量组与模型组比较,大鼠累计不动总时间均明显降低,差异具有显著性意义(P<0.05);益气排郁复方高、中剂量组与逍遥散组比较,大鼠累计不动总时间均明显降低,差异具有显著性意义(P<0.05)
模型组与假手术组比较,大鼠悬尾绝望状态时间明显升高,差异具有显著性意义(P<0.01)。益气排郁复方中剂量组与模型组比较,大鼠累计不动总时间均明显降低,差异具有显著性意义(P<0.05)。
3.4大鼠子宫脏器指数
上端以输卵管下缘为界,下端以阴道和子宫颈交界处为界分离大鼠子宫,保证子宫完整状态下清理周围脂肪后置于微量电子秤,称量子宫脏器并计算其指数。
表5 益气排郁复方对围绝经期抑郁症模型大鼠脏器指数的影响
注:与假手术组比较,▲▲P<0.01;与模型组比较,*P<0.05,**P<0.01;与逍遥散组比较,##P<0.01.
表5结果显示,治疗4周后,模型组与假手术组比较,大鼠体重、子宫重量及其指数均明显下降,差异具有显著性意义(P<0.01).益气排郁复方高、中、低剂量组与模型组比较,大鼠子宫重量增加,差异具有显著性意义(P<0.05,P<0.01);益气排郁复方中剂量组与模型组比较,大鼠子宫脏器指数增加,差异具有显著性意义(P<0.05)。
3.5益气排郁复方对围绝经期抑郁症模型大鼠血清中激素含量和炎性因子的影响
取材前12h禁食不禁水,3%戊巴比妥钠溶液大鼠腹腔注射麻醉后,腹主动脉采血,每只鼠均采集全血5ml,室温静置2小时,使用离心机3500r/min离心15分钟,ELISA法检测大鼠血清中E2、FSH、LH、IL-1β、IL-6、IL-18的含量。
表6 益气排郁复方对围绝经期抑郁症模型大鼠血清中激素含量的影响
注:与假手术组比较,▲▲P<0.01;与模型组比较,*P<0.05,**P<0.01;与逍遥散组比较,#P<0.05,##P<0.01.
表6结果显示,治疗4周后,模型组与假手术组比较,大鼠血清中E2含量降低,FSH和LH含量升高,差异具有显著性意义(P<0.01)。益气排郁复方高、中、低剂量组、舒肝解郁胶囊组和逍遥散组与模型组比较,大鼠血清中E2含量明显升高,FSH和LH含量明显降低,差异具有显著性意义(P<0.05,P<0.01);益气排郁复方高、中、低剂量组与和逍遥散组比较,大鼠血清中E2含量明显升高,FSH和LH含量明显降低,差异具有显著性意义(P<0.05,P<0.01)。
表7 益气排郁复方对围绝经期抑郁症模型大鼠血清中炎症因子的影响
注:与假手术组比较,▲▲P<0.01;与模型组比较,*P<0.05,**P<0.01;与逍遥散组比较,#P<0.05,##P<0.01.
表7结果显示,治疗4周后,模型组与假手术组比较,大鼠血清中IL-1β、IL-6和IL-18含量均升高,差异具有显著性意义(P<0.01)。益气排郁复方高、中、低剂量组及疏肝解郁胶囊组与模型组比较,大鼠血清中IL-1β含量明显降低,差异具有显著性意义(P<0.05,P<0.01);益气排郁复方高、中、低剂量组与模型组比较,大鼠血清中IL-6含量明显降低,差异具有显著性意义(P<0.05);益气排郁复方高、中剂量组与模型组比较,大鼠血清中IL-18含量明显降低,差异具有显著性意义(P<0.05);益气排郁复方高、中、低剂量组与逍遥散组比较,大鼠血清中IL-1β、IL-6和IL-18含量明显降低,差异具有显著性意义(P<0.05,P<0.01)。
3.6益气排郁复方对围绝经期抑郁症模型大鼠前额叶区NLRP3和NF-κBP65蛋白表达的影响
采用Western blot检测大鼠前额叶区NLRP3和NF-κBP65蛋白的表达。
表8益气排郁复方对围绝经期抑郁症模型大鼠前额叶区NLRP3和NF-κBP65蛋白表达的影响/>
注:与假手术组比较,▲▲P<0.01;与模型组比较,*P<0.05,**P<0.01;与逍遥散组比较,#P<0.05,##P<0.01.
表8结果显示,治疗4周后,模型组与假手术组比较,大鼠前额叶中NLRP3蛋白表达明显升高,NF-κBP65蛋白表达明显降低,差异具有显著性意义(P<0.01)。益气排郁复方高、中、低剂量组、疏肝解郁胶囊组及逍遥散组与模型组比较,大鼠前额叶中NLRP3蛋白表达明显降低,NF-κBP65蛋白表达明显升高,差异具有显著性意义(P<0.01);益气排郁复方高、中、低剂量组与逍遥散组比较,大鼠前额叶中NLRP3蛋白表达明显降低,NF-κBP65蛋白表达明显升高,差异具有显著性意义(P<0.01)。
从以上实验结论可以看出,益气排郁复方治疗后可显著地改善围绝经期抑郁症大鼠的抑郁样行为,并增加抑郁大鼠的体重和摄食,益气排郁复方通过增加血清雌二醇(E2),降低血清中卵泡刺激素(FSH)和黄体生成素(LH),提高子宫重量及脏器指数从而缓解OVX-CUMS诱导的下丘脑-垂体-卵巢(HPO)轴功能障碍。益气排郁复方可显著降低大鼠前额叶中神经炎症因子IL-1β、IL-6和IL-18的含量,降低大鼠前额叶中NLRP3mRNA蛋白表达,升高NF-κBP65mRNA蛋白。结论:益气排郁复方通过调节HPO轴功能障碍,激活NLRP3/NF-κBP65信号通路,降低大鼠前额叶组织中IL-1β、IL-6和IL-18炎症因子减轻神经炎症来改善大鼠的抑郁行为。
Claims (3)
1.一种用于治疗围绝经期抑郁症的中药组合物,其特征在于,所述中药组合物由以下重量配比的原料制备而成:当归15g、白芍15g、柴胡10g、茯苓15g、白术15g、炙甘草10g、生姜5g、薄荷5g、黄芪15g、西洋参10g、小麦30g、大枣5g、酸枣仁15g、柏子仁15g、麦冬15g以及五味子10g;所述中药组合物通过以下方法制备:
(1)按照重量配比称取各原料药,将各原料药混合均匀,加入原料药总重量10倍的蒸馏水,浸泡1小时后,再煎煮1小时,冷却;
(2)将步骤(1)冷却后的药液用纱布过滤,得到第一次滤液;
(3)取步骤(2)过滤后的药物残渣,重复步骤(1)和(2)得到第二次滤液,合并二次滤液;
(4)将步骤(3)中合并的二次滤液,干燥,得干膏;
(5)将得到的干膏粉碎、研磨,即得干粉状的所述中药组合物。
2.根据权利要求1所述的中药组合物,其特征在于,所述步骤(4)中干燥条件为:电热恒温鼓风干燥箱内,干燥温度为70℃,干燥时间为5d。
3.权利要求1或2所述中药组合物在制备治疗围绝经期抑郁症药物上的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210815024.7A CN115137803B (zh) | 2022-07-12 | 2022-07-12 | 一种治疗围绝经期抑郁症的中药组合物及其制备方法与应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210815024.7A CN115137803B (zh) | 2022-07-12 | 2022-07-12 | 一种治疗围绝经期抑郁症的中药组合物及其制备方法与应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115137803A CN115137803A (zh) | 2022-10-04 |
CN115137803B true CN115137803B (zh) | 2023-12-08 |
Family
ID=83413149
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210815024.7A Active CN115137803B (zh) | 2022-07-12 | 2022-07-12 | 一种治疗围绝经期抑郁症的中药组合物及其制备方法与应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115137803B (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101766801A (zh) * | 2010-02-09 | 2010-07-07 | 山西大学 | 逍遥散抗抑郁症有效部位及其提取方法 |
CN104873927A (zh) * | 2015-05-12 | 2015-09-02 | 杭州美誉医药有限公司 | 一种治疗月经不调的中药制剂、制备方法及应用 |
-
2022
- 2022-07-12 CN CN202210815024.7A patent/CN115137803B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101766801A (zh) * | 2010-02-09 | 2010-07-07 | 山西大学 | 逍遥散抗抑郁症有效部位及其提取方法 |
CN104873927A (zh) * | 2015-05-12 | 2015-09-02 | 杭州美誉医药有限公司 | 一种治疗月经不调的中药制剂、制备方法及应用 |
Non-Patent Citations (3)
Title |
---|
中药治疗更年期妇女抑郁症临床观察;唐丽芬;吴琏;;中医杂志;-;第-卷(第S1期);第160-162页 * |
甘麦大枣汤合黛力新治疗抑郁症42例;周美红;;山东中医杂志;-;第-卷(第03期);第178页 * |
逍遥散合甘麦大枣汤加减治疗产后抑郁症56例;雷福云;;中国民族民间医药;-;第-卷(第15期);第60页 * |
Also Published As
Publication number | Publication date |
---|---|
CN115137803A (zh) | 2022-10-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN104547579A (zh) | 一种治疗高泌乳素血症性不孕的药物组合物及其应用 | |
CN102058715B (zh) | 一种治疗慢性前列腺炎的中药制剂及其制备方法 | |
CN104922543A (zh) | 一种治疗闭经的药物组合物及其制备方法 | |
CN104984297A (zh) | 一种药物组合物在制备治疗闭经药物中的用途 | |
CN101797301A (zh) | 一种预防和治疗中老年便秘的药物 | |
CN104208418A (zh) | 一种固精缩尿补肾的金樱子保健口服液及其制备方法 | |
CN102988675B (zh) | 一种治疗慢性前列腺炎的中药组合物及其制备方法 | |
CN101904961A (zh) | 一种治疗各型痛经的中药制剂及其制备方法 | |
CN100528220C (zh) | 舒肝清热、健脾养血的妇科中成药及其制备方法 | |
CN103041262B (zh) | 一种治疗慢性前列腺炎的中药灌肠剂及其制备方法 | |
CN103386077A (zh) | 一种用于治疗痛经及子宫内膜异位症的复方中药及其制备方法 | |
CN115137803B (zh) | 一种治疗围绝经期抑郁症的中药组合物及其制备方法与应用 | |
CN105250556A (zh) | 一种用于治疗多囊卵巢综合征的中药药物 | |
CN101332282B (zh) | 一种治疗肾虚阴冷所致妇科疾病的中药组合物及制备方法 | |
CN103301353B (zh) | 一种治疗萎缩性阴道炎的药物组合物 | |
CN105943758B (zh) | 一种治疗不孕症的中药组合物及其应用 | |
CN103479783A (zh) | 一种治疗更年期抑郁症的中药组合物及其应用 | |
CN105796782A (zh) | 一种预防和或治疗多囊卵巢综合征的中药组合物及其制备方法和用途 | |
CN104721474A (zh) | 一种治疗习惯性流产的中药制剂及其制备方法 | |
CN104826076A (zh) | 一种治疗妊娠咳嗽的中药制剂及其制备方法 | |
CN103301373A (zh) | 一种治疗产后会阴粘膜病变的药物组合物 | |
CN103110722B (zh) | 用于治疗慢性盆腔炎的中药及其制备方法 | |
CN105796783A (zh) | 一种预防和/或治疗多囊卵巢综合征的胶囊 | |
CN102755567B (zh) | 一种治疗肝郁气滞痰浊阻络型月经失调的中药制剂 | |
CN106038802A (zh) | 治疗妇女卵巢早衰的中药组合物制备方法及其组合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |