CN109692263B - Compound traditional Chinese medicine and application thereof in treating prostatic hyperplasia - Google Patents
Compound traditional Chinese medicine and application thereof in treating prostatic hyperplasia Download PDFInfo
- Publication number
- CN109692263B CN109692263B CN201910035363.1A CN201910035363A CN109692263B CN 109692263 B CN109692263 B CN 109692263B CN 201910035363 A CN201910035363 A CN 201910035363A CN 109692263 B CN109692263 B CN 109692263B
- Authority
- CN
- China
- Prior art keywords
- parts
- traditional chinese
- chinese medicine
- compound traditional
- prostatic hyperplasia
- 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
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 title claims abstract description 73
- 208000004403 Prostatic Hyperplasia Diseases 0.000 title claims abstract description 73
- 239000003814 drug Substances 0.000 title claims abstract description 61
- 150000001875 compounds Chemical class 0.000 title claims abstract description 37
- 241000209020 Cornus Species 0.000 claims abstract description 25
- 241000893536 Epimedium Species 0.000 claims abstract description 25
- 240000005739 Eurycoma longifolia Species 0.000 claims abstract description 25
- 235000018905 epimedium Nutrition 0.000 claims abstract description 25
- 239000000284 extract Substances 0.000 claims abstract description 25
- 244000223760 Cinnamomum zeylanicum Species 0.000 claims abstract description 24
- 235000017803 cinnamon Nutrition 0.000 claims abstract description 24
- 240000008022 Rauvolfia verticillata Species 0.000 claims abstract description 22
- 229940079593 drug Drugs 0.000 claims abstract description 18
- 235000002732 Allium cepa var. cepa Nutrition 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 244000291564 Allium cepa Species 0.000 claims abstract 3
- 238000000605 extraction Methods 0.000 claims description 46
- 239000000463 material Substances 0.000 claims description 34
- 238000000926 separation method Methods 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 210000000582 semen Anatomy 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000003826 tablet Substances 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- 239000004530 micro-emulsion Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 244000061121 Rauvolfia serpentina Species 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 239000008215 water for injection Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 abstract description 29
- 230000000694 effects Effects 0.000 abstract description 26
- 210000004369 blood Anatomy 0.000 abstract description 22
- 239000008280 blood Substances 0.000 abstract description 22
- 210000003734 kidney Anatomy 0.000 abstract description 17
- 201000010099 disease Diseases 0.000 abstract description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 16
- 208000024891 symptom Diseases 0.000 abstract description 12
- 230000007812 deficiency Effects 0.000 abstract description 10
- 230000008506 pathogenesis Effects 0.000 abstract description 9
- 208000004880 Polyuria Diseases 0.000 abstract description 6
- 210000004185 liver Anatomy 0.000 abstract description 4
- 230000004069 differentiation Effects 0.000 abstract description 3
- 208000032023 Signs and Symptoms Diseases 0.000 abstract description 2
- 238000002309 gasification Methods 0.000 abstract description 2
- 235000008331 Pinus X rigitaeda Nutrition 0.000 abstract 1
- 235000011613 Pinus brutia Nutrition 0.000 abstract 1
- 241000018646 Pinus brutia Species 0.000 abstract 1
- 239000000047 product Substances 0.000 description 23
- 238000011282 treatment Methods 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 238000010298 pulverizing process Methods 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 10
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 9
- 206010071289 Lower urinary tract symptoms Diseases 0.000 description 8
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 241000234282 Allium Species 0.000 description 7
- 244000014047 Polianthes tuberosa Species 0.000 description 7
- 235000016067 Polianthes tuberosa Nutrition 0.000 description 7
- 102100035703 Prostatic acid phosphatase Human genes 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 210000003932 urinary bladder Anatomy 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 5
- 230000035619 diuresis Effects 0.000 description 5
- 206010020718 hyperplasia Diseases 0.000 description 5
- 230000027939 micturition Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 210000002700 urine Anatomy 0.000 description 5
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 4
- 239000002677 5-alpha reductase inhibitor Substances 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 230000004087 circulation Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 201000001881 impotence Diseases 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 208000017497 prostate disease Diseases 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 229960003604 testosterone Drugs 0.000 description 4
- 229940126680 traditional chinese medicines Drugs 0.000 description 4
- 208000017667 Chronic Disease Diseases 0.000 description 3
- 208000010228 Erectile Dysfunction Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- 230000006020 chronic inflammation Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 206010013990 dysuria Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229960004039 finasteride Drugs 0.000 description 3
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 2
- 102100033875 3-oxo-5-alpha-steroid 4-dehydrogenase 2 Human genes 0.000 description 2
- 229940113178 5 Alpha reductase inhibitor Drugs 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 101000640851 Homo sapiens 3-oxo-5-alpha-steroid 4-dehydrogenase 2 Proteins 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- 241000208332 Rauvolfia Species 0.000 description 2
- DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 description 2
- 206010046555 Urinary retention Diseases 0.000 description 2
- 208000031975 Yang Deficiency Diseases 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 229960003473 androstanolone Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 229960004199 dutasteride Drugs 0.000 description 2
- JWJOTENAMICLJG-QWBYCMEYSA-N dutasteride Chemical compound O=C([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)N[C@@H]4CC3)C)CC[C@@]21C)NC1=CC(C(F)(F)F)=CC=C1C(F)(F)F JWJOTENAMICLJG-QWBYCMEYSA-N 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000024121 nodulation Effects 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 238000011458 pharmacological treatment Methods 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 229960002613 tamsulosin Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 210000001635 urinary tract Anatomy 0.000 description 2
- 230000003202 urodynamic effect Effects 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- 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 1
- 108010029908 3-oxo-5-alpha-steroid 4-dehydrogenase Proteins 0.000 description 1
- 102000001779 3-oxo-5-alpha-steroid 4-dehydrogenase Human genes 0.000 description 1
- 206010069632 Bladder dysfunction Diseases 0.000 description 1
- 206010071445 Bladder outlet obstruction Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 description 1
- VAPSMQAHNAZRKC-PQWRYPMOSA-N Epristeride Chemical compound C1C=C2C=C(C(O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)NC(C)(C)C)[C@@]1(C)CC2 VAPSMQAHNAZRKC-PQWRYPMOSA-N 0.000 description 1
- 206010020853 Hypertonic bladder Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000021891 Micturition disease Diseases 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 101150098694 PDE5A gene Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- QZVCTJOXCFMACW-UHFFFAOYSA-N Phenoxybenzamine Chemical compound C=1C=CC=CC=1CN(CCCl)C(C)COC1=CC=CC=C1 QZVCTJOXCFMACW-UHFFFAOYSA-N 0.000 description 1
- 206010038967 Retrograde ejaculation Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 1
- 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 1
- 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
- 208000003800 Urinary Bladder Neck Obstruction Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 206010047141 Vasodilatation Diseases 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229960004607 alfuzosin Drugs 0.000 description 1
- WNMJYKCGWZFFKR-UHFFFAOYSA-N alfuzosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(C)CCCNC(=O)C1CCCO1 WNMJYKCGWZFFKR-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 210000005226 corpus cavernosum Anatomy 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 229960001389 doxazosin Drugs 0.000 description 1
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 235000005686 eating Nutrition 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000011841 epidemiological investigation Methods 0.000 description 1
- 229950009537 epristeride Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 239000008239 natural water Substances 0.000 description 1
- 230000008035 nerve activity Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 206010029446 nocturia Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000018052 penile erection Effects 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- 229960003418 phenoxybenzamine Drugs 0.000 description 1
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 208000026455 prostate symptom Diseases 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- 230000036299 sexual function Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229960004953 silodosin Drugs 0.000 description 1
- PNCPYILNMDWPEY-QGZVFWFLSA-N silodosin Chemical compound N([C@@H](CC=1C=C(C=2N(CCCO)CCC=2C=1)C(N)=O)C)CCOC1=CC=CC=C1OCC(F)(F)F PNCPYILNMDWPEY-QGZVFWFLSA-N 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229960001693 terazosin Drugs 0.000 description 1
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960001712 testosterone propionate Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000008727 tongluo Substances 0.000 description 1
- 229940126672 traditional medicines Drugs 0.000 description 1
- 206010046459 urethral obstruction Diseases 0.000 description 1
- 208000014001 urinary system disease Diseases 0.000 description 1
- 201000002327 urinary tract obstruction Diseases 0.000 description 1
- 238000007487 urography Methods 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 210000001835 viscera Anatomy 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)
- A61K36/24—Apocynaceae (Dogbane family), e.g. plumeria or periwinkle
-
- 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)
-
- 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)
- A61K36/29—Berberidaceae (Barberry family), e.g. barberry, cohosh or mayapple
- A61K36/296—Epimedium
-
- 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)
- A61K36/40—Cornaceae (Dogwood 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)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
-
- 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
- A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a compound traditional Chinese medicine and application thereof in treating prostatic hyperplasia, wherein the compound traditional Chinese medicine comprises the following raw materials in parts by weight: 0.5-2 parts of rauvolfia verticillata, 1-5 parts of epimedium, 1-5 parts of eurycoma longifolia, 1-5 parts of dogwood, 1-5 parts of cinnamon and 1-5 parts of tuber onion seed. The compound traditional Chinese medicine prescription is a proved safe and efficient prescription which is derived from the ancestors of the general manager of forest, pine and the limited biotechnology of Xian Song Tianle Ji and is tried by folk volunteers for over 30 years, the compound traditional Chinese medicine of the invention is based on the pathogenesis, has exquisite compatibility and great medicinal specificity, takes tonifying liver and kidney of epimedium, dogwood and the like as the main part, treats the deficiency of kidney yang, is supplemented with qi-promoting and diuresis-promoting, blood stasis-removing and stranguria-treating medicines of rauvolfia verticillata, Eurycoma longifolia extract and the like, treats the blood stasis and the unfavorable symptoms of bladder gasification; the whole formula treats the prostate by differentiation of symptoms and signs and integrally conditions, achieves the effect of treating both principal and secondary aspect of disease, and can effectively treat the benign prostatic hyperplasia.
Description
Technical Field
The invention belongs to the field of traditional Chinese medicines, and particularly relates to a compound traditional Chinese medicine and application thereof in treating prostatic hyperplasia.
Background
Prostatic hyperplasia, often referred to as Benign Prostatic Hyperplasia (BPH), is one of the most common diseases causing micturition disorders in elderly men, and is also one of the most common diseases in urology. Along with the aging of global population, the incidence of prostatic hyperplasia increases with age, but the prostate hyperplasia does not necessarily have clinical symptoms when suffering from hyperplasia pathological changes, and the symptoms such as dysuria and the like of most patients increase along with the increase of age; the incidence of diseases in cities and towns is higher than that in villages, and the ethnic difference also influences the proliferation degree. Mainly manifested by hyperplasia of interstitial and glandular components of prostate in histology, enlargement of prostate in anatomy, urinary bladder outlet obstruction, and clinical symptoms mainly including Lower Urinary Tract Symptoms (LUTS)[1]. LUTS includes symptoms during urination period including frequent micturition, urgency, nocturia, urinary incontinence, etc., symptoms during urination period including dysuria, thin urine flow, waiting for urine, dribbling after urination, etc., all of which are mainly manifested by dysuria[2]. Due to the improvement of living standard and the change of eating habit, the excessive protein and fat intake by human body leads prostate cells to obtain more nutrition and propagate in large quantities, thereby leading to the improvement of living standard and the change of eating habitHyperplasia of prostate gland[3]. It has also been shown that chronic inflammation may also be an important factor affecting prostate growth and the progression of lower urinary tract symptoms[4](ii) a Kim et al[5]The study showed that 181 of 225 subjects, i.e. 80% of BPH patients, found a combination with chronic inflammation of the prostate. Gandaglia et al[6]Studies suggest that focusing on BPH patients' association with chronic inflammation is critical for preventing BPH progression and developing targeted therapies.
Chinese traditional medicine considers that the prostatic hyperplasia belongs to the category of urine retention, which is the expression of descending turbidity and opening and closing dysfunction caused by the unfavorable qi transformation of kidney. The unobstructed flow of urine depends on the normal qi transformation of the bladder and triple energizer, and the essential qi of the kidney, i.e. "kidney yang", is the essence of the kidney. The traditional Chinese medicine differentiation is carried out on BP, and the main etiology and pathogenesis of BP are divided into deficiency of kidney qi, stagnation of lung qi, accumulation of damp-heat and blood stasis. Xufusong[7]It is considered that deficiency and excess should be considered first, and deficiency is mostly kidney yang deficiency, and it is indicated for tonifying kidney, regulating qi, softening hardness and dissipating nodulation; excess syndrome is mostly due to damp-heat and blood stasis, and is indicated for clearing heat and promoting diuresis, removing blood stasis and dissipating nodulation. Li Yue Qing[8]The basic pathogenesis of the disease is 'kidney deficiency and blood stasis', the treatment is advocated mainly by tonifying kidney and activating blood, and the practice proves that the symptoms can be improved as long as qi is smooth. Dachunfu is based on blood stasis, mainly promotes blood circulation to remove blood stasis, and promotes diuresis, so as to remove hyperplasia caused by blood stasis, promote blood circulation to promote water circulation, and alleviate adverse qi transformation of bladder[9]. Wangchen considers that blood stasis is the most important in pathogenesis and that the first important point in treatment is to dredge[10]. Qin nationality considers that the disease belongs to kidney deficiency, blood stasis, water retention and bladder dysfunction, the treatment is based on strengthening the primordial qi and tonifying deficiency, and the treatment is based on removing blood stasis and removing food retention[11]. Song Chunsheng, etc[12]According to the theory of collateral diseases, prostate diseases also belong to the pathological changes of collaterals, and it is considered that the local pathogenesis of prostate diseases is that collaterals are obstructed, the overall pathogenesis is that the collaterals of lung are obstructed, and the basic principle of treating prostate diseases is to dredge collaterals according to the theory of 'collaterals are obstructed'. Although the etiology and pathogenesis of BPH are complex, the core of its pathogenesis is not within the scope of the deficiency or excess of the origin. The occurrence and development of BPH is a dynamically evolving process involving multiple viscera,Many systems, especially kidney qi, are involved in various pathological products (mainly damp-heat and blood stasis), and finally become syndromes of principal deficiency, secondary excess, and intermingled deficiency and excess.
Rapid and accurate diagnosis of BPH is critical to the treatment and recovery of patients. The international prostate symptom score (I-PSS) is a subjective reflection of the patient's LUTS severity and is the currently internationally accepted best means for determining the patient's symptom severity[13]. Many studies have shown that factors such as age, serum PSA, prostate volume, maximal urinary flow rate, residual urine volume, and I-PSS score correlate with clinical progression of BPH, and are now used in the diagnosis of clinical BPH. For male patients over 50 who complain about LUTS, the possibility of BPH should be considered first. For definitive diagnosis, initial clinical assessments are made, including medical history inquiry, physical examination, urine routine examination, serum PSA examination, ultrasound examination of the prostate, and uroflow rate examination. After the initial assessment, further examinations may be selected based on the assessment results, including a urination diary, a blood creatinine assay, a venous urography, a urethrography, a urodynamics examination, a urethrocystoscopy, and an ultrasound examination of the upper urinary tract[14]。
It has been reported that BPH incidence in US 60-69 years old men is 70%, and after 70 years of age, BPH incidence rises to 80%[15]. Looking after six[16]BPH in china in the 50 th of the 20 th century was reported to account for 7.6% of urological disorders, with an increase to 18.5% in the 90 s. In Pulin et al[17]The survey of the aged over 60 years old in 6 cities in China revealed that the total incidence of BPH was 43.68%, and the incidence rates were 34.48%, 46.77% and 60.19% by age 60, 70 and 80, respectively. In epidemiological investigation of several common diseases in areas such as Beijing, Shanghai, Guangzhou, Chengdu, Xian and Shenyang, different authors reported that BPH is the first common disease among the elderly[18]. Peace of mind and body[19]The chronic diseases of the military retired old people in Fuzhou region of China are investigated, and the incidence rate of BPH is found to be the first of 10 common diseases. Although the incidence of BPH varies from region to region, the incidence of BPH is on the rise in general and has become the most common of the elderlyThe chronic disease of (1).
In recent years, with the introduction of several new drugs for treating BPH, BPH has been converted from an acute surgical disease to a chronic disease. The drugs that have been marketed for the treatment of BPH mainly include four major classes, α 1-ARs antagonists, 5 α -reductase inhibitors, phosphodiesterase 5 inhibitors and plant inhibitors[20]。
α 1-ARs antagonists have been widely used in the treatment of BPH for kinetic factors since the mid 80's of the last century. Such compounds relax prostate smooth muscle by blocking sympathetic nerve activity, increasing high urinary flow rates and alleviating other symptoms in BPH patients. The first type of non-selective alpha 1/alpha 2 receptor antagonist, phenoxybenzamine, blocks both the alpha 1 receptor and the pre-synaptic alpha 2 receptor, causing the release of norepinephrine, resulting in increased heart rate and myocardial contractility, causing undesirable systemic side effects. With the advent of α 1-ARs highly selective antagonists such as prazosin, terazosin, doxazosin, alfuzosin and tamsulosin, the pharmacological treatment of BPH is greatly improved. Side effects due to vasodilatation are reduced compared to the first generation, but because of lack of subtype selectivity and tissue selectivity, second generation antagonists are also associated with side effects such as postural hypotension, dizziness, weakness, etc. The tamsulosin orally disintegrating tablet is a new preparation form of the medicine, is suitable for patients who strictly limit water intake and old people who have dysphagia, has clinical research and verification of the safety and the effectiveness thereof, has no obvious change of blood pressure during the administration period, and has no obvious increase of the incidence rate of erectile dysfunction[21]. The drug is also found to have good effect in the combined medication scheme of 5 alpha-reductase inhibitor, anticholinergic drug and the like[22]. The third generation alpha 1 receptor antagonist, silodosin, has enhanced selectivity for α 1A-AR, which is abundantly distributed in prostate tissue, and acts selectively on smooth muscle cells located in prostate and bladder, and has less influence on α 1-AR subtypes at other sites, and has become a first-line clinical drug for treating BPH/LUTS. The medicine has small dosage, can quickly relieve the urinary tract obstruction symptom caused by BPH, but has the side effects of retrograde ejaculation, erectile dysfunction and the like clinically; therefore, the young and the patients with normal sexual life should be cautiousHeavy use medicine[23]。
Steroid 5 α -reductase is an NADPH-dependent enzyme that is widely present in the prostate and converts testosterone into dihydrotestosterone, which is essential for glandular enlargement. 5 alpha-reductase inhibitors (5-ARIs) reduce prostate volume, alleviate the static factors of urethral obstruction and alleviate LUTS by inhibiting the conversion of testosterone to dihydrotestosterone, thereby ameliorating symptoms while reducing the risk of acute urinary retention and reducing the need for surgical intervention[24]. However, the safety of long-term use thereof has been proved by studies to be accompanied by side effects of decreased libido, impotence and ejaculation dysfunction. The 5-ARIs commonly used internationally are dutasteride and finasteride, and the epristeride is also used domestically. Dutasteride is a competitive inhibitor of type I and type II 5 alpha-reductase, can reduce the level of DHT in plasma and prostate, has 60 times of inhibition effect on type I enzyme than finasteride, and has strong inhibition effect on type II enzyme. Finasteride is a selective type II 5 alpha-reductase inhibitor, and can reduce DHT level in blood plasma without affecting testosterone level, and has less influence on normal sexual life and libido[25]。
Phosphodiesterases (PDEs) have the function of hydrolyzing intracellular second messengers (cAMP, cyclic adenosine monophosphate or cGMP, cyclic guanosine monophosphate), degrading intracellular cAMP or cGMP levels, thus terminating the biochemical role conducted by these second messengers. Phosphodiesterase 5 is widely expressed in the corpora cavernosa, bladder, prostate and urinary tract and other tissues of the penis and is regulated by the NO/cGMP signal transduction mechanism in the urogenital tract during penile erection, relaxation of prostate smooth muscle, and attenuation of detrusor hyperreflexia[26]. PDE5 has become a clear target for the treatment of erectile dysfunction, and has been more recently reported as one of the therapeutic targets of BPH27]。
In summary, in the current treatment methods for treating BPH, surgical treatment operations are prone to complications; the variety of the drugs which can be used for treatment in the drug treatment is few, the side effects of the alpha 1-ARs antagonist and the 5-ARIs which are effective in the treatment are obvious, the sexual function is influenced in different degrees, and with the accelerated aging process, BPH patients in all countries around the world are in an ascending trend. Therefore, it is very important to find a therapeutic agent for BPH with a definite therapeutic effect from Chinese traditional medicines. The compound traditional Chinese medicine prescription is a proved safe and efficient prescription which is derived from the ancestors of the Lin-Xingsong-pine general manager of the Xian-Song-Tianle-Ji-Biotech Limited company and is tried out by folk volunteers for over 30 years, and the prescription is prepared from epimedium, dogwood, rauvolfia verticillate, Eurycoma longifolia, cinnamon, semen allii tuberosi and other natural medicines through extraction and refining, has the effects of tonifying liver and kidney, promoting qi circulation and diuresis, removing blood stasis and treating stranguria, and is mainly used for treating BPH and the like.
Disclosure of Invention
The invention provides a compound traditional Chinese medicine which is characterized by comprising the following raw materials in parts by weight: 0.5-2 parts of rauvolfia verticillata, 1-5 parts of epimedium, 1-5 parts of eurycoma longifolia, 1-5 parts of dogwood, 1-5 parts of cinnamon and 1-5 parts of tuber onion seed. Preferably 0.5-1.0 part of rauvolfia verticillata, 1-2 parts of epimedium, 1-2 parts of eurycoma longifolia, 1-2 parts of dogwood, 1-2 parts of cinnamon and 1-2 parts of semen allii tuberosi.
Another embodiment of the invention provides a compound traditional Chinese medicine extract, which is characterized in that the compound traditional Chinese medicine extract is prepared from the following raw material medicines in parts by weight: 0.5-2 parts of rauvolfia verticillata, 1-5 parts of epimedium, 1-5 parts of eurycoma longifolia, 1-5 parts of dogwood, 1-5 parts of cinnamon and 1-5 parts of tuber onion seed. Preferably 0.5-1.0 part of rauvolfia verticillata, 1-2 parts of epimedium, 1-2 parts of eurycoma longifolia, 1-2 parts of dogwood, 1-2 parts of cinnamon and 1-2 parts of semen allii tuberosi.
Another embodiment of the present invention provides a method for preparing the compound traditional Chinese medicine extract, which is characterized by comprising the following steps:
(1) according to the weight parts, the rauvolfia verticillata, the epimedium herb, the eurycoma longifolia, the dogwood, the cinnamon and the semen allii tuberosi are crushed and mixed evenly to obtain a material;
(2) adding the material obtained in the step (1) into an extraction kettle, and adopting supercritical CO2Extracting to obtain the compound traditional Chinese medicine extract; wherein the extraction pressure is 26-30MPa, the extraction temperature is 50-55 ℃, and CO is added2The flow is 50-60L/h, the extraction time is 60-90min, the temperature of the separation kettle I is 40-45 ℃, the pressure is 8-10MPa, the temperature of the separation kettle II is 35-40 ℃, and the pressure is 5-6 MPa.
The invention also provides application of the compound traditional Chinese medicine, the compound traditional Chinese medicine extract and/or the pharmaceutically acceptable salt thereof in preparing medicines for preventing and/or treating prostatic hyperplasia or related diseases caused by prostatic hyperplasia.
Another embodiment of the present invention provides a pharmaceutical composition for preventing and/or treating prostatic hyperplasia or related diseases caused by prostatic hyperplasia, which is characterized in that the pharmaceutical composition comprises the above compound traditional Chinese medicine extract and/or its pharmaceutically acceptable salt as an active ingredient. The pharmaceutical composition optionally further comprises other drugs for preventing and/or treating prostatic hyperplasia or related diseases caused by prostatic hyperplasia. The pharmaceutical composition may further comprise pharmaceutically acceptable adjuvants (such as water for injection, pharmaceutically acceptable carrier, surfactant, diluent, excipient, antioxidant, stabilizer, solubilizer, etc.). The dosage form of the pharmaceutical composition may be a solid formulation, a liquid formulation or a semi-solid formulation. Preferably capsules, tablets, suspensions, microemulsions, submicroemulsions or injections.
The devilpepper, the epimedium herb, the eurycoma longifolia, the dogwood, the cinnamon and the semen allii tuberosi can be Chinese medicinal materials, Chinese medicinal decoction pieces or natural plants (dried).
The term "pharmaceutically acceptable salts" according to the present invention refers to non-toxic inorganic or organic acid and/or base addition salts. See, e.g., "Salt selection for basic drugs", int.J. pharm. (1986),33, 201-.
The various dosage forms related to the pharmaceutical composition of the present invention can be prepared into preparations meeting the requirements of clinical treatment and/or prevention of prostatic hyperplasia according to the technical specifications and requirements of the pharmaceutical field (for example, methods in pharmacopoeia, textbooks or other prior arts, and similar methods described in patent application nos. 201710594462.4 and 201710983187.5), and various suitable specifications and dosage forms (including solid preparations, liquid preparations and semi-solid preparations) such as capsules, tablets, suspensions, microemulsions, submicron emulsions or various injections containing the same single or multi-component combinations.
The preparation method of the dosage form related to the pharmaceutical composition of the invention belongs to the conventional preparation method in the field of pharmacy, and can be realized by the technical personnel in the field according to the prior art (such as pharmacopoeia, textbook and other technical specifications in the pharmaceutical field).
Compared with the prior art, the invention has the advantages that: (1) the compound traditional Chinese medicine prescription is from the proved safe and efficient proved by trial of 30 over years of folk volunteers by Lin-Xingsong-pine general manager ancestors of Xian Song-Tianle-Ji-Biotechnology Limited company, is prepared from natural medicines such as epimedium, dogwood, rauvolfia verticillata, Eurycoma longifolia, cinnamon, semen allii tuberosi and the like through extraction and refining, and has the effects of tonifying liver and kidney, promoting qi circulation, inducing diuresis, removing blood stasis and treating stranguria; (2) the compound traditional Chinese medicine is in a state of being in focus on the pathogenesis, has precise and appropriate compatibility and great medicine specificity, takes epimedium and dogwood for tonifying liver and kidney, treats the kidney-yang deficiency, is supplemented with rauvolfia verticillata and eurycoma longifolia for promoting qi circulation and inducing diuresis, removing blood stasis and treating stranguria, is matched with cinnamon and tuber onion seed medicines for tonifying kidney and supporting yang, and treats the blood stasis and the adverse symptoms of bladder gasification; the whole formula treats the prostate by differentiation of symptoms and signs, integrally conditions, achieves the effect of treating both principal and secondary aspect of disease, and can effectively treat the benign prostatic hyperplasia; (3) the six traditional Chinese medicines in the compound traditional Chinese medicine are absent, particularly, the rauvolfia verticillata has the effect of remarkably enhancing the drug effects of the other five traditional Chinese medicines, and the dosage of the compound traditional Chinese medicine is very important.
Detailed Description
In order to facilitate a further understanding of the invention, the following examples are provided to illustrate it in more detail. However, these examples are only for better understanding of the present invention and are not intended to limit the scope or the principle of the present invention, and the embodiments of the present invention are not limited to the following.
Example 1
Chinese medicinal materials: 50g of rauvolfia verticillata, 200g of epimedium herb, 200g of eurycoma longifolia, 200g of dogwood, 100g of cinnamon and 100g of semen allii tuberose.
Pulverizing the above Chinese medicinal materials, and mixing to obtain materials; adding into extraction kettle, and using supercritical CO2Extracting to obtain compound Chinese medicinal extract 12.56g (hereinafter referred to as product A); wherein the extraction pressure is 26MPa, the extraction temperature is 55 ℃, and CO is added2The flow rate is 50L/h, the extraction time is 90min, the temperature of the separation kettle I is 45 ℃, and the pressure is 8MPa, the temperature of the separation kettle II is 40 ℃, and the pressure is 5 MPa.
Example 2
Chinese herbal pieces: 200g of rauvolfia verticillata, 500g of epimedium herb, 500g of eurycoma longifolia, 500g of dogwood, 500g of cinnamon and 500g of tuber onion seed.
Pulverizing the above Chinese medicinal decoction pieces, and mixing to obtain material; adding into extraction kettle, and using supercritical CO2Extracting to obtain 41.12g of Chinese medicinal extract (hereinafter referred to as product B); wherein the extraction pressure is 30MPa, the extraction temperature is 50 ℃, and CO is added2The flow rate is 60L/h, the extraction time is 60min, the temperature of the separation kettle I is 40 ℃, the pressure is 10MPa, the temperature of the separation kettle II is 35 ℃, and the pressure is 6 MPa.
Example 3
Chinese medicinal materials: 50g of rauvolfia verticillata, 100g of epimedium herb, 100g of eurycoma longifolia, 100g of dogwood, 100g of cinnamon and 100g of semen allii tuberose.
Pulverizing the above Chinese medicinal materials, and mixing to obtain materials; adding into extraction kettle, and using supercritical CO2Extracting to obtain 7.52g of Chinese medicinal extract (hereinafter referred to as product C); wherein the extraction pressure is 28MPa, the extraction temperature is 53-55 ℃, and CO is added2The flow is 55L/h, the extraction time is 70min, the temperature of the separation kettle I is 43-45 ℃, the pressure is 9MPa, the temperature of the separation kettle II is 38-40 ℃, and the pressure is 6 MPa.
Example 4
Chinese medicinal materials: 100g of rauvolfia verticillata, 200g of epimedium herb, 200g of eurycoma longifolia, 200g of dogwood, 200g of cinnamon and 200g of tuber onion seed.
Pulverizing the above Chinese medicinal materials, and mixing to obtain materials; adding into extraction kettle, and using supercritical CO2Extracting to obtain 15.18g of compound Chinese medicinal extract (hereinafter referred to as product D); wherein the extraction pressure is 28MPa, the extraction temperature is 50-52 ℃, and CO is added2The flow rate is 52L/h, the extraction time is 75min, the temperature of the separation kettle I is 40-42 ℃, the pressure is 8MPa, the temperature of the separation kettle II is 35-37 ℃, and the pressure is 5 MPa.
Example 5
Chinese herbal pieces: 50g of rauvolfia verticillata, 500g of epimedium herb, 500g of eurycoma longifolia, 500g of dogwood, 500g of cinnamon and 500g of tuber onion seed.
Pulverizing the above Chinese medicinal decoction pieces, mixingObtaining the material; adding into extraction kettle, and using supercritical CO2Extracting to obtain 39.86g of Chinese medicinal extract (hereinafter referred to as product E); wherein the extraction pressure is 30MPa, the extraction temperature is 50 ℃, and CO is added2The flow rate is 60L/h, the extraction time is 60min, the temperature of the separation kettle I is 40 ℃, the pressure is 10MPa, the temperature of the separation kettle II is 35 ℃, and the pressure is 6 MPa.
Example 6
Chinese medicinal materials: 200g of rauvolfia verticillata, 100g of epimedium herb, 100g of eurycoma longifolia, 100g of dogwood, 100g of cinnamon and 100g of semen allii tuberose.
Pulverizing the above Chinese medicinal materials, and mixing to obtain materials; adding into extraction kettle, and using supercritical CO2Extracting to obtain compound Chinese medicinal extract 8.23g (hereinafter referred to as product F); wherein the extraction pressure is 28MPa, the extraction temperature is 53-55 ℃, and CO is added2The flow is 50L/h, the extraction time is 90min, the temperature of the separation kettle I is 43-45 ℃, the pressure is 8MPa, the temperature of the separation kettle II is 38-40 ℃, and the pressure is 5 MPa.
Example 7
Chinese medicinal materials: 200g of epimedium, 200g of eurycoma longifolia, 200g of dogwood, 100g of cinnamon and 100g of tuber onion seed.
Pulverizing the above Chinese medicinal materials, and mixing to obtain materials; adding into extraction kettle, and using supercritical CO2Extracting to obtain compound Chinese medicinal extract 9.78G (hereinafter referred to as product G); wherein the extraction pressure is 26MPa, the extraction temperature is 55 ℃, and CO is added2The flow rate is 50L/h, the extraction time is 90min, the temperature of the separation kettle I is 45 ℃, the pressure is 8MPa, the temperature of the separation kettle II is 40 ℃, and the pressure is 5 MPa.
Example 8
Chinese medicinal materials: 10g of rauvolfia verticillata, 200g of epimedium herb, 200g of eurycoma longifolia, 200g of dogwood, 100g of cinnamon and 100g of semen allii tuberose.
Pulverizing the above Chinese medicinal materials, and mixing to obtain materials; adding into extraction kettle, and using supercritical CO2Extracting to obtain compound Chinese medicinal extract 10.15g (hereinafter referred to as product H); wherein the extraction pressure is 26MPa, the extraction temperature is 55 ℃, and CO is added2The flow rate is 50L/h, the extraction time is 90min, the temperature of the separation kettle I is 45 ℃, the pressure is 8MPa, the temperature of the separation kettle II is 40 ℃, and the pressure is 5 MPa.
Example 9
Chinese medicinal materials: 500g of rauvolfia verticillata, 100g of epimedium herb, 100g of eurycoma longifolia, 100g of dogwood, 100g of cinnamon and 100g of semen allii tuberose.
Pulverizing the above Chinese medicinal materials, and mixing to obtain materials; adding into extraction kettle, and using supercritical CO2Extracting to obtain 11.53g of compound Chinese medicinal extract (hereinafter referred to as product I); wherein the extraction pressure is 28MPa, the extraction temperature is 53-55 ℃, and CO is added2The flow is 50L/h, the extraction time is 90min, the temperature of the separation kettle I is 43-45 ℃, the pressure is 8MPa, the temperature of the separation kettle II is 38-40 ℃, and the pressure is 5 MPa.
Example 10
Chinese medicinal materials: 50g of rauvolfia verticillata, 200g of epimedium herb, 200g of eurycoma longifolia, 200g of dogwood, 100g of cinnamon and 100g of semen allii tuberose.
Pulverizing the above Chinese medicinal materials, and mixing to obtain materials; extracting with 3.0L water under reflux for 24 hr, filtering, concentrating, and vacuum drying to obtain compound Chinese medicinal extract 9.12g (hereinafter referred to as product J).
Example 11
Chinese medicinal materials: 50g of rauvolfia verticillata, 200g of epimedium herb, 200g of eurycoma longifolia, 200g of dogwood, 100g of cinnamon and 100g of semen allii tuberose.
Pulverizing the above Chinese medicinal materials, and mixing to obtain materials; extracting with 95% ethanol (3.0L) under reflux for 24 hr, filtering, concentrating, and vacuum drying to obtain compound Chinese medicinal extract 10.68g (hereinafter referred to as product K).
Example 12 animal experiments
1.1 Experimental animals
Male C57BL/6 mice: SPF grade, 6 weeks old, 18-22g weight, raised in IVC environment, provided by the university of air force military laboratory animals center, license number SCXK (force) 2012-0007. The required feed (produced by Jiangsu province cooperative medical and biological engineering Limited liability company), the drinking water (natural water drunk by farmer spring: production permit number SC 10661032600241, produced by Taibaishan beverage Limited company in Shaanxi province), the Schekebeta SPF-grade selected shaving pad (produced by Jiangsu province cooperative medical and biological engineering Limited liability company) and the like are all commercially available standard products.
1.2 reagents and reagents
The products A to K were prepared by the method described in examples 1 to 11 of the present invention, by the Biotech Co., Ltd. Testosterone propionate injection (TP), batch No. 201709101, available from Shanghai Tong pharmaceutical industry Co., Ltd. Sertraline tablet (SNT), lot No. 20170211, from the pharmaceutical factory of Nanjing Meirui. Prostatic Acid Phosphatase (PAP) kit (batch No. 20171105), testosterone (T) kit (batch No. 20171217), estradiol (E)2) The kits (batch No. 20171013) were all produced by Shanghai Jianglai Biotech Co., Ltd.
2.1 Experimental methods
2.1.1 animal models: the mouse BPH model was replicated according to the literature [28] and mice were randomized after 1 week of acclimation. The TP injection is diluted by using edible peanut oil of Gongyu brand, mice are injected with 5mg/kgTP dilution every day subcutaneously, and the mice are randomly divided into model groups, namely a BPH group and reagent groups (products A-K and SNT which are prepared into aqueous suspension during administration) after 28 consecutive days, and a normal control group is additionally arranged, so that 14 groups are formed, and each group is 12. At the same time of molding, the normal control mice and the model group mice are perfused with physiological saline with the same volume as the stomach every day; the reagent groups are respectively mixed according to the set dose [ product A-K dose: 40 mg/(kg. 3d), SNT dose: the mice were gavaged with 200 mg/(kg. d) (total volume in one gavage was in the range of 0.01 mL/g) for 28 consecutive days.
2.2.2 detection indexes: the next day after the last administration of the drug, the blood was collected from the eyeball, and the prostate tissue was washed in cold physiological saline to remove blood stain and absorb water, and then weighed to calculate the prostate index. Contracting the collected blood at 4 deg.C for 30min, centrifuging at 3000r/min for 20min to obtain supernatant, and detecting PAP activity in serum according to the operation of each kit instruction T, E2And (4) content.
2.2.3 statistical analysis: the experimental result adopts the average number +/-standard error
Showing that the statistical analysis of the experimental data is completed by using SPSS18.0 statistical software; students t-test, P<0.05 and P<The 0.01 secondary represents the degree of significant difference in the data.
3 results of the experiment
3.1 Effect of reagent on prostate wet weight, index in BPH mice: the results are shown in Table 1.
TABLE 1 Effect of the test drugs on prostate wet weight and index in BPH mice
Denotes P <0.01 compared to model group, and denotes P <0.05 compared to model group.
Compared with a blank control group, the prostate wet weight and the prostate index of the mouse are obviously increased (P <0.01), which indicates that the BPH model is successfully replicated. Each reagent group is administrated for 28 days, the wet weight of the prostate (P <0.05 or P <0.01) and the prostate index (P <0.05 or P <0.01) of the prostate of the mouse are obviously reduced; but especially the A-F group of the product has more obvious effect (P is less than 0.01); the proportion of the six traditional Chinese medicines is proved, and particularly the dosage of the rauwolfia plays an important role in the drug effect.
3.2 Each reagent pairs BPH mouse serum T, E2And PAP effects: the results are shown in Table 2.
TABLE 2 Effect of each reagent on serum T, E2 and PAP in BPH mice
Denotes P <0.01 compared to model group, and denotes P <0.05 compared to model group.
T, E in serum of BPH model mouse2The content and the PAP activity are obviously improved (P)<0.01); compared with the product, the T content in the serum of mice in the product A-K (especially the product A-F) group is obviously reduced (P)<0.05 or P<0.01), it can be seen that the content of DHT converted from T by 5 α -reductase is correspondingly reduced, thereby inhibiting BPH; the products A-K (especially products A-F) can make the mouse serum E2The content is remarkably lower than that of (P)<0.05 or P<0.01), the estrogen content is reduced, which has important effect on inhibiting BPH, and can obviously reduce the content of androgen DHT receptor in the cytosol of prostate tissue, thereby realizing the anti-BPH activity; the A-K (especially A-F) groups can obviously reduce the enzyme activity (P) of the serum PAP of BPH mice<0.05 or P<0.01), a significant decrease in PAP enzyme activity is indicative of inhibition of prostate hyperplasia in BPH mice. The results also show that the compound traditional Chinese medicine (products A-F) prepared according to the formula is used for reducing the BPH mouse serum T, E2Has higher content and PAP enzyme activity (P)<0.01)。
All documents mentioned in this application are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications can be made by those skilled in the art after reading the above disclosure, and equivalents also fall within the scope of the invention as defined by the appended claims.
Reference to the literature
1. The fruit-macro-peak, the hydroxuridine-group, interpretation and related research progress of the diagnostic and therapeutic guidelines for benign prostatic hyperplasia [ J ]. modern practical medicine 2014,26(10):1193-1195.
2. Zhang Chun He, Chen Tianbo, Qin national administration, etc. the correlation between the traditional Chinese medicine syndrome type and the urodynamic parameters of benign prostatic hyperplasia [ J ]. the journal of Chinese Male science 2007,1(02): 185-188).
3. Aetiology analysis of Murphy prostate hyperplasia [ J ] clinical medicine electronics journal.2017, 4(79):15641-15642.
4.Hu J,Zhang L,Zou L,et al.Role of inflammation in benign prostatic hyperplasia development among Han Chinese:A population-based and single-institutional analysis[J].International Journal of Urology.2016,22(12):1138-1142.
5.Sang H K,Jung K I,Koh J S,et al.Lower Urinary Tract Symptoms in Benign Prostatic Hyperplasia Patients:Orchestrated by Chronic Prostatic Inflammation and Prostatic Calculi？[J].Urologia Internationalis.2013,90(2):144-149.
6.Gandaglia G,Briganti A,Gontero P,et al.The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH)[J].Bju International.2013,112(4):432-441.
7. Sun self-study, Li Peng Chao, research progress of Chinese medicine for treating benign prostatic hyperplasia [ J ] Chinese medicine journal 2018,33(06): 2482-.
8. Zhang Chun He, Li Hai Song, Li Yue Qing teach the experience of treating prostatic hyperplasia [ J ]. Chinese clinician 2003,1(03):56-57.
9. Zhao Jian Ye, Dai Chun Fu Zi teach the blood circulation method for treating prostatic hyperplasia [ J ]. Fujian Chinese medicine, 2004,3(02):21-22.
10. Experience of li dong. Wangchen professor for treating benign prostatic hyperplasia [ J ] Chinese traditional medicine journal 2011,26(02): 286-.
11. Yangyanjia, Suzi Feng, experience of professor Qin national political education in treating prostatic hyperplasia [ J ]. Yunnan J.2005, 3(01):8-9 of Chinese traditional medicine.
12. Song Chunsheng, Zhao Jia, Tongluo method for treating prostate diseases will be appreciated [ J ]. J.J.2013, 54(12):1060 and 1061.
13. Gu-cash-En, Wang Jia Jing, Zhang Jun, etc. grading management mode of prostatic hyperplasia patients [ J ]. Chinese medical journal.2014, 49(01):20-22.
14. Wuqing nations urodynamic examination the progress of the study in patients with prostatic hyperplasia [ J ]. Degjiang medicine 2016,44(06): 726-.
15.Pandya,Chirayu,Pillai,et al.Association of Cadmium and Lead with Antioxidant Status and Incidence of；Benign Prostatic Hyperplasia in Patients of Western India[J].Biological Trace Element Research.2013,152(3):316-326.
16. Sixth, epidemiology of benign prostatic hyperplasia and prostate cancer [ J ] New medicine 2000,1(09): 521-.
17. Pulin, Zhenghong, Suhong school, etc. the prevalence of prostatic hyperplasia in the elderly in six cities of China and related factors [ J ]. J.Zhonghua epidemiology J.2000, 2(04):36-39.
18. Zhenghong, in Pulin, Gaoyang, et al, six diseases cross-sectional survey of aged people in six cities in China in 1997 [ J ]. J.J.Zhonghua aged medicine.2000, 2(03):54-57.
19. Monweiping, Linshine, Weihong, etc. the army in Fuzhou area leaves the investigation and analysis of the health status of retired elderly [ J ] the liberty preventive medicine journal [ 2000,1(05): 337-plus 340 ].
20. Zhangbaozhong, Lijiabin, Liwangwei, and the like, progress of drug research for treating benign prostatic hyperplasia [ J ]. Guangdong chemical industry 2017,44(12): 148-.
21.Fusco F,Palmieri A,Ficarra V,et al.α1-Blockers Improve Benign Prostatic Obstruction in Men with Lower Urinary Tract Symptoms:A Systematic Review and Meta-analysis of Urodynamic Studies[J].European Urology.2016,69(6):1091-1011.
22. Panpei, Lugangguo. alpha. (1A) -receptor antagonist research New progress [ J ]. China journal of pharmacy 2006,3(20):1521-1524.
23. Progress of pharmacological treatment of benign prostatic hyperplasia [ J ] medical review 2015,21(14):2599-2601.
24.Nicholson T M,Ricke W A.Androgens and estrogens in benign prostatic hyperplasia:past,present and future[J].Differentiation.2011,82(4):184-199.
25.Carrasquillo R J,Nealy S W,Wang D S.5-Alpha-reductase inhibitors in diseases of the prostate[J].Current Opinion in Endocrinology Diabetes&Obesity.2014,21(6):488-492.
26.Carson C C,Rosenberg M,Kissel J,et al.Tadalafil-a therapeutic option in the management of BPH-LUTS[J].International Journal of Clinical Practice.2013,68(1):94-103.
27.Gacci M,Andersson K E,Chapple C,et al.Latest Evidence on the Use of Phosphodiesterase Type 5Inhibitors for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia[J].European Urology.2016,70(1):124-133.
28.QIAN Hua，GAO Zhihui，et al.Urtica dioica extract for the treatment of benign prostatic hyperplasia in mice[J].Chin Pharm J，2008，43(2)：108-110.
Claims (10)
1. The compound traditional Chinese medicine extract for preventing and/or treating prostatic hyperplasia is characterized by being prepared from the following raw material medicines in parts by weight: 0.5-2 parts of rauvolfia verticillata, 1-5 parts of epimedium, 1-5 parts of eurycoma longifolia, 1-5 parts of dogwood, 1-5 parts of cinnamon and 1-5 parts of tuber onion seed.
2. The compound traditional Chinese medicine extract as claimed in claim 1, which is characterized in that the compound traditional Chinese medicine extract is prepared from the following raw material medicines in parts by weight: 0.5-1.0 part of rauvolfia verticillata, 1-2 parts of epimedium, 1-2 parts of eurycoma longifolia, 1-2 parts of dogwood, 1-2 parts of cinnamon and 1-2 parts of semen allii tuberosi.
3. The preparation method of the compound traditional Chinese medicine extract as claimed in any one of claims 1 to 2, which is characterized by comprising the following steps:
(1) the method comprises the following steps of (1) crushing and uniformly mixing the devilpepper, the epimedium herb, the eurycoma longifolia, the dogwood, the cinnamon and the tuber onion seeds according to the weight part of any one of the claims 1 to 2 to obtain a material;
(2) adding the material obtained in the step (1) into an extraction kettle, and adopting supercritical CO2Extracting to obtain the compound traditional Chinese medicine extract; wherein the extraction pressure is 26-30MPa, the extraction temperature is 50-55 ℃, and CO is added2The flow is 50-60L/h, the extraction time is 60-90min, the temperature of the separation kettle I is 40-45 ℃, the pressure is 8-10MPa, the temperature of the separation kettle II is 35-40 ℃, and the pressure is 5-6 MPa.
4. The use of the compound traditional Chinese medicine extract of any one of claims 1-2 in the preparation of a medicament for preventing and/or treating prostatic hyperplasia.
5. A pharmaceutical composition for preventing and/or treating prostatic hyperplasia, characterized in that the pharmaceutical composition comprises the compound traditional Chinese medicine extract of any one of claims 1-2 as an effective ingredient.
6. The pharmaceutical composition of claim 5, further comprising optionally other agents for preventing and/or treating prostatic hyperplasia.
7. Pharmaceutical composition according to any one of claims 5 to 6, characterized in that it further comprises pharmaceutically acceptable adjuvants.
8. The pharmaceutical composition according to claim 7, wherein the pharmaceutically acceptable excipient is selected from the group consisting of water for injection, surfactants, diluents, stabilizers, solubilizers.
9. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition is in the form of a solid, liquid or semisolid formulation.
10. The pharmaceutical composition of claim 9, wherein the pharmaceutical composition is in the form of a capsule, tablet, suspension, microemulsion, or injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910035363.1A CN109692263B (en) | 2019-01-15 | 2019-01-15 | Compound traditional Chinese medicine and application thereof in treating prostatic hyperplasia |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910035363.1A CN109692263B (en) | 2019-01-15 | 2019-01-15 | Compound traditional Chinese medicine and application thereof in treating prostatic hyperplasia |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109692263A CN109692263A (en) | 2019-04-30 |
| CN109692263B true CN109692263B (en) | 2021-06-25 |
Family
ID=66233297
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910035363.1A Active CN109692263B (en) | 2019-01-15 | 2019-01-15 | Compound traditional Chinese medicine and application thereof in treating prostatic hyperplasia |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109692263B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1537588A (en) * | 2003-04-20 | 2004-10-20 | 毛友昌 | Wenshen Qianlie granule for warming kidney and treating prostatic disorders, and its prepn. method |
| CN106421245A (en) * | 2016-09-29 | 2017-02-22 | 福建农林大学 | Compound plant-caused transdermal patch for treating prostatic hyperplasia and preparation method thereof |
| CN108096313A (en) * | 2018-02-06 | 2018-06-01 | 张南 | A kind of pharmaceutical composition for treating virile diesae and its preparation method and application |
-
2019
- 2019-01-15 CN CN201910035363.1A patent/CN109692263B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1537588A (en) * | 2003-04-20 | 2004-10-20 | 毛友昌 | Wenshen Qianlie granule for warming kidney and treating prostatic disorders, and its prepn. method |
| CN106421245A (en) * | 2016-09-29 | 2017-02-22 | 福建农林大学 | Compound plant-caused transdermal patch for treating prostatic hyperplasia and preparation method thereof |
| CN108096313A (en) * | 2018-02-06 | 2018-06-01 | 张南 | A kind of pharmaceutical composition for treating virile diesae and its preparation method and application |
Non-Patent Citations (1)
| Title |
|---|
| 前列腺增生症证治琐谈;赵语华等;《河北中医》;20030630;第25卷(第06期);458-459 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109692263A (en) | 2019-04-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100337662C (en) | Medicinal composition for treating hyperlipemia and its preparing method | |
| Ji et al. | Shen-ling-bai-zhu-san, a spleen-tonifying Chinese herbal formula, alleviates lactose-induced chronic diarrhea in rats | |
| WO2019154161A1 (en) | Pharmaceutical composition for treating male diseases, and preparation method therefor and use thereof | |
| Zhang et al. | The Chinese medicinal herb decoction QRZSLXF enhances anti-inflammatory effect in TNBS-induced colitis via balancing Th17/Tregs differentiation | |
| Liu et al. | Chebulanin exerts its anti-inflammatory and anti-arthritic effects via inhibiting NF-κB and MAPK activation in collagen-induced arthritis mice | |
| CN101032580A (en) | Medicine for treating rheumatic diseases | |
| CN106138210A (en) | Butterflybush flower and the application of the medicine as preparation treatment hypertensive cardiopathy for the extract thereof | |
| WO2016190785A1 (en) | Bisamide derivative of dicarboxylic acid as an agent for stimulating tissue regeneration and recovery of diminished tissue function | |
| CN109692263B (en) | Compound traditional Chinese medicine and application thereof in treating prostatic hyperplasia | |
| WO2020187017A1 (en) | Traditional chinese medicine composition for relaxing bowels to relieve constipation, preparation method therefor and application thereof | |
| CN105902553A (en) | Compound finasteride tablets and preparation process thereof | |
| CN105168284A (en) | Application of panax japonicus saponins V and total panax japonicus saponins thereof to preparation of medicament for resisting urathritis | |
| JP2002003391A (en) | Medicinal agent and composition using acanthopanax senticosus harms and method for extracting the same | |
| CN1857337B (en) | Use of patrinia herb and its extract in preparing medicine for treating prostatic hyperplasia | |
| CN111407783B (en) | Application of penthorum chinense pursh in preparation of medicine for treating high proteinuria | |
| CN105663192A (en) | Novel application of notoginseng in preparation of medicine for treating and/or preventing prostatitis | |
| CN101897714B (en) | Use of paeoniflorin | |
| CN1814244A (en) | Chinese medicine suppository for treating liver fiberosis and hysteromyoma and preparing method | |
| CN104257960A (en) | Traditional Chinese medicine composition for treating non-alcoholic fatty liver disease and applications of composition | |
| CN113633712B (en) | Traditional Chinese medicine composition for treating gout and oral preparation based on traditional Chinese medicine composition | |
| CN101480424B (en) | Medicine for treating prostatosis and method for preparing same | |
| Vardhini Samuel et al. | Increasing incidence of Diabetes Mellitus, Systemic hypertension and Germ Cells with endogenous estrogen | |
| CN104116794B (en) | A kind of Chinese medicine assisting treatment obesity-related hypertension | |
| CN105878998A (en) | Pharmaceutical preparation for hyperplasia of prostate | |
| Cai‑hong et al. | The latest research progress of novel coronavirus" Omicron sub‑variant BA. 5". |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20240301 Address after: Room 2009, Jiaqi City Investment Company Building, High tech Industrial Park, Dongsheng District, Ordos City, Inner Mongolia Autonomous Region Patentee after: Ordos Jiuyi Biotechnology Co.,Ltd. Country or region after: China Address before: Room 201, 2nd floor, former United Front Work Department, Jianguo lane, Jianguo Road, Xi'an, Shaanxi 710005 Patentee before: Lin Sisong Country or region before: China Patentee before: Wang Siwang |