CN108771662A - 紫檀芪在制备防治高尿酸肾病的药物中的用途 - Google Patents
紫檀芪在制备防治高尿酸肾病的药物中的用途 Download PDFInfo
- Publication number
- CN108771662A CN108771662A CN201810644954.4A CN201810644954A CN108771662A CN 108771662 A CN108771662 A CN 108771662A CN 201810644954 A CN201810644954 A CN 201810644954A CN 108771662 A CN108771662 A CN 108771662A
- Authority
- CN
- China
- Prior art keywords
- pterostilbene
- purposes
- pharmaceutically acceptable
- drug
- preparation
- 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.)
- Pending
Links
- VLEUZFDZJKSGMX-UHFFFAOYSA-N pterostilbene Natural products COC1=CC(OC)=CC(C=CC=2C=CC(O)=CC=2)=C1 VLEUZFDZJKSGMX-UHFFFAOYSA-N 0.000 title claims abstract description 39
- VLEUZFDZJKSGMX-ONEGZZNKSA-N pterostilbene Chemical compound COC1=CC(OC)=CC(\C=C\C=2C=CC(O)=CC=2)=C1 VLEUZFDZJKSGMX-ONEGZZNKSA-N 0.000 title claims abstract description 39
- 239000003814 drug Substances 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims description 12
- 208000017169 kidney disease Diseases 0.000 title claims description 5
- 201000001431 Hyperuricemia Diseases 0.000 title description 3
- 229940079593 drug Drugs 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 210000003734 kidney Anatomy 0.000 claims description 20
- 206010029164 Nephrotic syndrome Diseases 0.000 claims description 19
- 208000009928 nephrosis Diseases 0.000 claims description 19
- 231100001027 nephrosis Toxicity 0.000 claims description 19
- 206010016654 Fibrosis Diseases 0.000 claims description 18
- 230000004761 fibrosis Effects 0.000 claims description 18
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims description 13
- 229940116269 uric acid Drugs 0.000 claims description 13
- 210000002966 serum Anatomy 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 9
- 102000016359 Fibronectins Human genes 0.000 claims description 8
- 108010067306 Fibronectins Proteins 0.000 claims description 8
- 239000004615 ingredient Substances 0.000 claims description 8
- 102000012422 Collagen Type I Human genes 0.000 claims description 7
- 108010022452 Collagen Type I Proteins 0.000 claims description 7
- 230000000295 complement effect Effects 0.000 claims description 6
- 239000000470 constituent Substances 0.000 claims description 5
- 210000003205 muscle Anatomy 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 102000007469 Actins Human genes 0.000 claims description 4
- 108010085238 Actins Proteins 0.000 claims description 4
- 102000002734 Collagen Type VI Human genes 0.000 claims description 4
- 108010043741 Collagen Type VI Proteins 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 206010046337 Urate nephropathy Diseases 0.000 abstract 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 8
- -1 ion salt Chemical class 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000004043 dyeing Methods 0.000 description 7
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 6
- 229960003459 allopurinol Drugs 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 210000005239 tubule Anatomy 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 206010003694 Atrophy Diseases 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 206010023421 Kidney fibrosis Diseases 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 206010028851 Necrosis Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000037444 atrophy Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000017074 necrotic cell death Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 210000005084 renal tissue Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical group C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- RJWUMFHQJJBBOD-UHFFFAOYSA-N 2-methylheptadecane Chemical compound CCCCCCCCCCCCCCCC(C)C RJWUMFHQJJBBOD-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- OEYQBKYISMRWQB-UHFFFAOYSA-N Santal Chemical compound C=1C(OC)=CC(O)=C(C2=O)C=1OC=C2C1=CC=C(O)C(O)=C1 OEYQBKYISMRWQB-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 230000024924 glomerular filtration Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 206010033675 panniculitis Diseases 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 235000021286 stilbenes Nutrition 0.000 description 2
- 210000004304 subcutaneous tissue Anatomy 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- 210000000626 ureter Anatomy 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- AXPZIVKEZRHGAS-UHFFFAOYSA-N 3-benzyl-5-[(2-nitrophenoxy)methyl]oxolan-2-one Chemical compound [O-][N+](=O)C1=CC=CC=C1OCC1OC(=O)C(CC=2C=CC=CC=2)C1 AXPZIVKEZRHGAS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000037823 Cerebral ischemia/reperfusion injury Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- HDWLUGYOLUHEMN-UHFFFAOYSA-N Dinobuton Chemical compound CCC(C)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1OC(=O)OC(C)C HDWLUGYOLUHEMN-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- IAPCTXZQXAVYNG-UHFFFAOYSA-M Potassium 2,6-dihydroxytriazinecarboxylate Chemical compound [K+].[O-]C(=O)C1=NC(=O)NC(=O)N1 IAPCTXZQXAVYNG-UHFFFAOYSA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010042033 Stevens-Johnson syndrome Diseases 0.000 description 1
- 231100000168 Stevens-Johnson syndrome Toxicity 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000425573 Talanes Species 0.000 description 1
- 206010044223 Toxic epidermal necrolysis Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 240000000851 Vaccinium corymbosum Species 0.000 description 1
- 235000003095 Vaccinium corymbosum Nutrition 0.000 description 1
- 235000017537 Vaccinium myrtillus Nutrition 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000021014 blueberries Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 150000007516 brønsted-lowry acids Chemical class 0.000 description 1
- 150000007528 brønsted-lowry bases Chemical class 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000007046 ethoxylation reaction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 1
- 229960000201 isosorbide dinitrate Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- YLGXILFCIXHCMC-JHGZEJCSSA-N methyl cellulose Chemical compound COC1C(OC)C(OC)C(COC)O[C@H]1O[C@H]1C(OC)C(OC)C(OC)OC1COC YLGXILFCIXHCMC-JHGZEJCSSA-N 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 229950000193 oteracil Drugs 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000011257 shell material Substances 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 239000012177 spermaceti Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- UAEJRRZPRZCUBE-UHFFFAOYSA-N trimethoxyalumane Chemical compound [Al+3].[O-]C.[O-]C.[O-]C UAEJRRZPRZCUBE-UHFFFAOYSA-N 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及紫檀芪在制备防治高尿酸肾病的药物中的用途,属于医药领域。本发明提供了紫檀芪或其药学上可接受的盐在制备治疗和/或预防高尿酸肾病的药物中的用途。实验结果表明,紫檀芪能够明显降低血尿酸水平,还具有抑制肾间质纤维化的作用,能够显著降低α‑SMA、collagen I、collagen IV、fibronectin等纤维化相关蛋白的表达量,对高尿酸肾病的治疗作用确切,为临床用药提供了一种新的选择。
Description
技术领域
本发明涉及紫檀芪在制备防治高尿酸肾病的药物中的用途,属于医药领域。
背景技术
高尿酸肾病是嘌呤代谢异常,血尿酸升高所引起的肾脏损害,早期可表现为尿浓缩功能减退,其后逐步出现肾小球滤过率下降,血肌酐升高,导致慢性肾功能不全。近年来,随着高尿酸血症发病率的日益提高,高尿酸肾病发病率显著逐年增高。因此,寻求高尿酸肾病的有效治疗药物,具有重要意义。
既往的研究证实,降低血尿酸水平可以延缓肾脏疾病的进展,因此,治疗高尿酸肾病重在降低血尿酸水平,防止尿酸盐沉积在肾脏。目前,临床上用于降尿酸的一线药物是别嘌呤醇,但其可引起皮肤过敏、骨髓抑制等不良反应,尤其是Stevens-Johnson综合征和中毒性表皮坏死松解,其死亡率达10%~40%,这些不良反应在一定程度上限制了别嘌呤醇的临床应用。而且,别嘌呤醇经肾脏代谢,对于肾功能不全患者往往需要根据肾小球滤过率调整剂量,否则患者不易耐受。鉴于别嘌呤醇存在的上述缺陷,亟需开发出新的替代药物。
紫檀芪是一种广泛存在于天然产物中的二苯乙烯类化合物,化学名为3,5-二甲氧基-4'-羟基反式二苯乙烯,分子式为C16H16O3,分子量为256.11,化学结构如下:
紫檀芪最初从檀香中分离得到,故得以命名,其后在蓝莓、葡萄等水果中均有发现。现代药理研究表明,紫檀芪具有多种药理活性,如抗肿瘤、抗氧化、抗衰老等,且具有较高的生物利用度,是当前研究的热点化合物之一。
发明内容
本发明的目的在于提供紫檀芪在制备防治高尿酸肾病的药物中的用途。
本发明提供了紫檀芪或其药学上可接受的盐在制备治疗和/或预防高尿酸肾病的药物中的用途。
进一步地,所述药物通过降低血尿酸水平防治高尿酸肾病。
进一步地,所述药物通过抑制肾间质纤维化防治高尿酸肾病。
本发明提供了紫檀芪或其药学上可接受的盐在制备治疗和/或预防肾间质纤维化的药物中的用途。
进一步地,所述药物降低α-平滑肌肌动蛋白、I型胶原、IV型胶原、纤连蛋白中一种或几种蛋白的表达。
本发明提供了紫檀芪或其药学上可接受的盐在制备降低血尿酸水平的药物中的用途。
进一步地,所述药物是以紫檀芪或其药学上可接受的盐为活性成分,加入药学上可接受的辅料或者辅助性成分,制备而成的制剂。
进一步地,所述制剂为口服制剂。
进一步地,每单位制剂含有紫檀芪2.75~5.5mg。
动物实验证明,紫檀芪在给药剂量为25~50mg/kg/d时对小鼠高尿酸肾病能够发挥显著的治疗作用。按成人体重70kg计算,换算出成人每天给药剂量范围为2.75mg~5.5mg。本发明所述每单位制剂对应成人每天给药剂量。
本发明提供了防治高尿酸肾病的药物组合物,它是以紫檀芪或其药学上可接受的盐为活性成分,加入药学上可接受的辅料或者辅助性成分,制备而成的制剂。
术语“药学上可接受的”是指某载体、运载物、稀释剂、辅料,和/或所形成的盐、酯通常在化学上或物理上与构成某药物剂型的其它成分相兼容,并在生理上与受体相兼容。
术语“药学上可接受的盐”是指本发明化合物与无机和/或有机酸和碱形成的酸式和/或碱式盐,也包括两性离子盐(内盐),还包括季铵盐,例如烷基铵盐。这些盐可以是在化合物的最后分离和纯化中直接得到。也可以是通过将上述化合物与一定数量的酸或碱适当(例如等当量)进行混合而得到。这些盐可能在溶液中形成沉淀而以过滤方法收集,或在溶剂蒸发后回收而得到,或在水介质中反应后冷冻干燥制得。本发明中所述盐可以是化合物的盐酸盐、硫酸盐、枸橼酸盐、苯磺酸盐、氢溴酸盐、氢氟酸盐、磷酸盐、乙酸盐、丙酸盐、丁二酸盐、草酸盐、苹果酸盐、琥珀酸盐、富马酸盐、马来酸盐、酒石酸盐或三氟乙酸盐。
本发明化合物或药物组合物的施用方式没有特别限制,代表性的施用方式包括(但并不限于):口服、肠胃外(静脉内、肌肉内或皮下)、和局部给药。
用于口服给药的固体剂型包括胶囊剂、片剂、丸剂、散剂和颗粒剂。在这些固体剂型中,活性化合物与至少一种常规惰性赋形剂(或载体)混合,如柠檬酸钠或磷酸二钙,或与下述成分混合:(a)填料或增容剂,例如,淀粉、乳糖、蔗糖、葡萄糖、甘露醇和硅酸;(b)粘合剂,例如,羟甲基纤维素、藻酸盐、明胶、聚乙烯基吡咯烷酮、蔗糖和***胶;(c)保湿剂,例如,甘油;(d)崩解剂,例如,琼脂、碳酸钙、马铃薯淀粉或木薯淀粉、藻酸、某些复合硅酸盐、和碳酸钠;(e)缓溶剂,例如石蜡;(f)吸收加速剂,例如,季胺化合物;(g)润湿剂,例如鲸蜡醇和单硬脂酸甘油酯;(h)吸附剂,例如,高岭土;和(i)润滑剂,例如,滑石、硬脂酸钙、硬脂酸镁、固体聚乙二醇、十二烷基硫酸钠,或其混合物。胶囊剂、片剂和丸剂中,剂型也可包含缓冲剂。
固体剂型如片剂、糖丸、胶囊剂、丸剂和颗粒剂可采用包衣和壳材制备,如肠衣和其它本领域公知的材料。它们可包含不透明剂,并且,这种组合物中活性化合物或化合物的释放可以延迟的方式在消化道内的某一部分中释放。可采用的包埋组分的实例是聚合物质和蜡类物质。必要时,活性化合物也可与上述赋形剂中的一种或多种形成微胶囊形式。
用于口服给药的液体剂型包括药学上可接受的乳液、溶液、悬浮液、糖浆或酊剂。除了活性化合物外,液体剂型可包含本领域中常规采用的惰性稀释剂,如水或其它溶剂,增溶剂和乳化剂,例知,乙醇、异丙醇、碳酸乙酯、乙酸乙酯、丙二醇、1,3-丁二醇、二甲基甲酰胺以及油,特别是棉籽油、花生油、玉米胚油、橄榄油、蓖麻油和芝麻油或这些物质的混合物等。
除了这些惰性稀释剂外,组合物也可包含助剂,如润湿剂、乳化剂和悬浮剂、甜味剂、矫味剂和香料。
除了活性化合物外,悬浮液可包含悬浮剂,例如,乙氧基化异十八烷醇、聚氧乙烯山梨醇和脱水山梨醇酯、微晶纤维素、甲醇铝和琼脂或这些物质的混合物等。
用于肠胃外注射的组合物可包含生理上可接受的无菌含水或无水溶液、分散液、悬浮液或乳液,和用于重新溶解成无菌的可注射溶液或分散液的无菌粉末。适宜的含水和非水载体、稀释剂、溶剂或赋形剂包括水、乙醇、多元醇及其适宜的混合物。
用于局部给药的本发明化合物的剂型包括软膏剂、散剂、贴剂、喷射剂和吸入剂。活性成分在无菌条件下与生理上可接受的载体及任何防腐剂、缓冲剂,或必要时可能需要的推进剂一起混合。
本发明所述药学上可接受的辅料,是指除活性成分以外包含在剂型中的物质。
本发明所述药学上可接受的辅助性成分,它具有一定生理活性,但该成分的加入不会改变上述药物组合物在疾病治疗过程中的主导地位,而仅仅发挥辅助功效,这些辅助功效仅仅是对该成分已知活性的利用,是医药领域惯用的辅助治疗方式。若将上述辅助性成分与本发明药物组合物配合使用,仍然应属于本发明保护的范围。
本发明提供了紫檀芪在制备防治高尿酸肾病的药物中的用途。实验结果表明,紫檀芪能够明显降低血尿酸水平,还具有抑制肾间质纤维化的作用,能够显著降低α-SMA、collagen I、collagen IV、fibronectin等纤维化相关蛋白的表达量,对高尿酸肾病的治疗作用确切,为临床用药提供了一种新的选择。
附图说明
图1为紫檀芪抑制小鼠肾间质纤维化的染色及评分结果图;
图2为α-平滑肌肌动蛋白α-SMA、I型胶原col I、IV型胶原col IV、纤连蛋白FN等纤维化标志蛋白的表达情况图;
图3为血尿酸水平检测结果图;
图4为高尿酸肾病小鼠肾脏组织MASSON染色图。
具体实施方式
本发明具体实施方式中使用的原料、设备均为已知产品,通过购买市售产品获得。
本发明提供了紫檀芪或其药学上可接受的盐在制备治疗和/或预防高尿酸肾病的药物中的用途。
目前,已报道紫檀芪所具有的药理活性为降血脂、抑制真菌、抗氧化、保护脑缺血/再灌注损伤和抗肿瘤,但尚无研究表明其对高尿酸肾病具有治疗作用。本发明创造性地发现了紫檀芪能够降低血尿酸水平、抑制肾间质纤维化,对高尿酸肾病具有确切的治疗作用,开发出了紫檀芪新的制药用途。
实施例1紫檀芪抑制肾间质纤维化的作用
实验动物:野生C57BL/6J小鼠。实验前至少1周恒温环境下标准化实验日粮饲养,饮水不限。
动物分组:将小鼠24只分为4组:①假手术组12只;②单侧输尿管结扎肾间质纤维化(UUO)模型组12只;③紫檀芪不同浓度治疗组(25mg/kg/d、50mg/kg/d)每组各6只。
造模方法:对小鼠进行麻醉。麻醉后判断肾脏大致体表投影位置后于小鼠左侧腹部剪开皮肤,钝性分离皮下组织及肌层,暴露左肾,沿肾蒂向肾下极方向寻找输尿管,在输尿管上段行双线结扎,两结扎点之间剪断输尿管,逐层缝合皮下组织及皮肤。造模后于术后第7天处死假手术组、UUO模型组、紫檀芪治疗组一半的小鼠,14天后处死另一半小鼠,抽取心脏血并留取肾脏组织收集标本。
给药方法:紫檀芪不同浓度治疗组于造模后第1天开始采用口服给药方式给予紫檀芪,连续14天;UUO模型组造模后在相同时间灌喂同等剂量生理盐水;假手术组在相同时间灌喂同等剂量生理盐水。
实验结果:
1、紫檀芪抑制小鼠肾间质纤维化的染色及评分结果(见图1)
HE染色和MASSON染色:显微镜下发现,假手术组的染色图片具有完整的肾脏结构,没有明显的肾小管变性、坏死,管状萎缩,没有炎性细胞浸润和纤维化。UUO模型组在第7天时可见肾小管有明显的扩张,MASSON染色蓝色区域明显(蓝色区域表示纤维化病变的程度),14天后病变更加明显。使用紫檀芪治疗后,虽然肾小管仍有明显扩张,但MASSON染色蓝色区域明显少于UUO模型组。
以上结果表明,在UUO模型组中,小鼠肾间质明显纤维化;使用紫檀芪进行治疗后,可以显著抑制肾间质纤维化的程度。
肾间质纤维化评分:评分标准:对每组MASSON涂片显微镜200倍视野下随机不同位置选取10个视野进行统计分析。根据肾小管变性和坏死、管状萎缩、炎性细胞浸润和纤维化的程度从无、轻度、中度到重度分别评分为0/1/2和3分。
评分结果:UUO组评分较假手术组显著增高,紫檀芪治疗组评分显著低于UUO组评分,且呈一定剂量依赖性。
2、WesternBlot检测α-平滑肌肌动蛋白(α-SMA)、I型胶原(col I)、IV型胶原(colIV)、纤连蛋白(FN)等纤维化标志蛋白的表达情况(见图2)
α-SMA、collagen I、collagen IV、fibronectin蛋白的表达量能够反映肾间质纤维化的程度。从图2可以看出,紫檀芪能显著抑制α-SMA、collagen I、collagen IV、fibronectin蛋白的表达,治疗肾间质纤维化的作用非常明显。
实施例2紫檀芪治疗高尿酸肾病的作用
实验动物:SPF级雄性C57BL/6J小鼠。实验前至少1周恒温环境下标准化实验日粮饲养,饮水不限。
动物分组:将小鼠40只分为4组:①正常对照组10只;②高尿酸肾病模型组10只;③紫檀芪治疗组(50mg/kg/d)10只;④阳性对照别嘌呤醇治疗组(5mg/kg/d)10只。
造模方法:根据小鼠体重以腺嘌呤100mg/kg、氧嗪酸钾1500mg/kg的比例,用蒸馏水将两者混合后制成终浓度为80g/L的混悬液,每日早晚灌胃,连续21天,建立高尿酸血症肾损害动物模型。21天后处死小鼠,腹主动脉取血,留取肾脏组织。
给药方法:紫檀芪和别嘌呤醇治疗组于造模后第1天开始采用口服给药方式给药,连续21天;模型组造模后在相同时间灌喂同等剂量生理盐水;正常对照组在相同时间灌喂同等剂量生理盐水。
实验结果:
1、血尿酸
实验动物取血后离心保留血清,使用Beckman全自动生化分析仪检测血尿酸含量,检测结果见图3。从图3可以看出,紫檀芪能显著降低血尿酸水平,效果与临床降尿酸一线药物别嘌呤醇相当。
2、MASSON染色
从图4可以看出,正常对照组的染色图片具有完整的肾脏结构,没有明显的肾小管变性、坏死,管状萎缩,没有炎性细胞浸润和纤维化。高尿酸肾病模型组可见肾小管有明显的扩张,MASSON染色蓝色区域明显(蓝色区域表示纤维化病变的程度)。使用紫檀芪治疗后,虽然肾小管仍有扩张,但MASSON染色蓝色区域明显少于模型组。
以上结果表明,紫檀芪可以显著抑制高尿酸肾病小鼠肾间质纤维化的程度。
Claims (10)
1.紫檀芪或其药学上可接受的盐在制备治疗和/或预防高尿酸肾病的药物中的用途。
2.如权利要求1所述的用途,其特征是:所述药物通过降低血尿酸水平防治高尿酸肾病。
3.如权利要求1所述的用途,其特征是:所述药物通过抑制肾间质纤维化防治高尿酸肾病。
4.紫檀芪或其药学上可接受的盐在制备治疗和/或预防肾间质纤维化的药物中的用途。
5.如权利要求4所述的用途,其特征是:所述药物降低α-平滑肌肌动蛋白、I型胶原、IV型胶原、纤连蛋白中一种或几种蛋白的表达。
6.紫檀芪或其药学上可接受的盐在制备降低血尿酸水平的药物中的用途。
7.如权利要求1~6任意一项所述的用途,其特征是:所述药物是以紫檀芪或其药学上可接受的盐为活性成分,加入药学上可接受的辅料或者辅助性成分,制备而成的制剂。
8.如权利要求7所述的用途,其特征是:所述制剂为口服制剂。
9.如权利要求7所述的用途,其特征是:每单位制剂含有紫檀芪2.75~5.5mg。
10.防治高尿酸肾病的药物组合物,其特征是:它是以紫檀芪或其药学上可接受的盐为活性成分,加入药学上可接受的辅料或者辅助性成分,制备而成的制剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810644954.4A CN108771662A (zh) | 2018-06-21 | 2018-06-21 | 紫檀芪在制备防治高尿酸肾病的药物中的用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810644954.4A CN108771662A (zh) | 2018-06-21 | 2018-06-21 | 紫檀芪在制备防治高尿酸肾病的药物中的用途 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN108771662A true CN108771662A (zh) | 2018-11-09 |
Family
ID=64025404
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810644954.4A Pending CN108771662A (zh) | 2018-06-21 | 2018-06-21 | 紫檀芪在制备防治高尿酸肾病的药物中的用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108771662A (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110772516A (zh) * | 2019-12-02 | 2020-02-11 | 四川大学华西医院 | 异紫堇定碱或其盐在制备降低血尿酸水平、防治尿酸性肾病的药品中的用途 |
CN113209060A (zh) * | 2021-06-17 | 2021-08-06 | 迈迪唯希科技(天津)有限公司 | 一种紫檀芪在制备预防和/或治疗肠上皮屏障损伤药物中的应用 |
-
2018
- 2018-06-21 CN CN201810644954.4A patent/CN108771662A/zh active Pending
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110772516A (zh) * | 2019-12-02 | 2020-02-11 | 四川大学华西医院 | 异紫堇定碱或其盐在制备降低血尿酸水平、防治尿酸性肾病的药品中的用途 |
CN110772516B (zh) * | 2019-12-02 | 2022-10-04 | 四川大学华西医院 | 异紫堇定碱或其盐在制备降低血尿酸水平、防治尿酸性肾病的药品中的用途 |
CN113209060A (zh) * | 2021-06-17 | 2021-08-06 | 迈迪唯希科技(天津)有限公司 | 一种紫檀芪在制备预防和/或治疗肠上皮屏障损伤药物中的应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2431025A1 (en) | Capsule formulation of pirfenidone and pharmaceutically acceptable excipients | |
DE69418252T2 (de) | Stabilisierte, feste pharmazeutische Zubereitung, die Dextromethorphan Phenylpropanolamine und Coffein enthält | |
JP2011116781A (ja) | 脳梗塞の予防及び治療用医薬品の製造におけるl−ブチルフタリドの使用 | |
CN100418535C (zh) | 一种七叶皂苷及其制备方法 | |
CN101134042A (zh) | 七叶皂苷的药物组合物及其制备方法和其用途 | |
AU745759B2 (en) | Application of substituted aminomethyl chromans in order to prevent neural degeneration and to promote neural regeneration | |
KR100381834B1 (ko) | 용출성이 개선된 프란루카스트 고체분산체 조성물 및 그제조 방법 | |
WO2012090194A2 (en) | Compositions and methods for treating a skin disorder | |
CN108771662A (zh) | 紫檀芪在制备防治高尿酸肾病的药物中的用途 | |
EP0277352B1 (de) | Synergistische Kombination von Azelastin und Theophyllin oder Azelastin und Beta-Mimetika | |
JP7090599B2 (ja) | ミネラルコルチコイド受容体拮抗薬を含む医薬組成物及びその使用 | |
JP2000500504A (ja) | Vx 478のようなhivプロテアーゼ阻害剤およびビタミンe―tpgsのような水溶性ビタミンeを含む組成物 | |
EP0981340B1 (fr) | Formulations pharmaceutiques presentees sous forme seche pour l'administration orale d'un compose ammonium quaternaire cyclique | |
DE2950154C2 (zh) | ||
DE69115528T2 (de) | Neue pharmazeutische Verwendungen von Forskolin-Derivaten | |
CN112755018A (zh) | 漆黄素在制备防治尿酸性肾病的药物中的用途 | |
CN108685907A (zh) | 防治肾损伤的化合物 | |
AU2003217704A1 (en) | Diphenhydramine tannate compositions and methods of use | |
CN108295067A (zh) | 防治肾间质纤维化的化合物 | |
CN113521082A (zh) | 雷公藤甲素在制备预防和/或治疗肝病的药物中的应用 | |
US20240041772A1 (en) | Sustained release formulations of dysoxylum binefacterum | |
JPH0535131B2 (zh) | ||
CN107281209B (zh) | 一种抗胃溃疡的药物组合物及其制备方法与用途 | |
CN100525780C (zh) | 一种复方灯盏花素滴丸 | |
TWI393562B (zh) | 左旋丁基苯酞在製備預防和治療腦梗塞的藥物中的應用 |
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 | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181109 |