CN104546982A - 乳香提取物在制备维持血管内皮稳态药物中的应用 - Google Patents
乳香提取物在制备维持血管内皮稳态药物中的应用 Download PDFInfo
- Publication number
- CN104546982A CN104546982A CN201410843006.5A CN201410843006A CN104546982A CN 104546982 A CN104546982 A CN 104546982A CN 201410843006 A CN201410843006 A CN 201410843006A CN 104546982 A CN104546982 A CN 104546982A
- Authority
- CN
- China
- Prior art keywords
- injection
- vascular endothelial
- extract
- frankincense
- emulsion
- 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
- 230000002792 vascular Effects 0.000 title claims abstract description 22
- 230000003511 endothelial effect Effects 0.000 title claims abstract description 19
- 239000003814 drug Substances 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 229940075000 frankincense extract Drugs 0.000 title abstract description 16
- 230000013632 homeostatic process Effects 0.000 title abstract description 10
- 230000006378 damage Effects 0.000 claims abstract description 14
- 239000000284 extract Substances 0.000 claims abstract description 11
- 210000003556 vascular endothelial cell Anatomy 0.000 claims abstract description 9
- 208000027418 Wounds and injury Diseases 0.000 claims abstract description 5
- 208000014674 injury Diseases 0.000 claims abstract description 5
- 230000037326 chronic stress Effects 0.000 claims abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 4
- 239000004863 Frankincense Substances 0.000 claims description 29
- 239000000839 emulsion Substances 0.000 claims description 29
- 238000002347 injection Methods 0.000 claims description 28
- 239000007924 injection Substances 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 7
- 239000003921 oil Substances 0.000 claims description 7
- 229960001295 tocopherol Drugs 0.000 claims description 7
- 229930003799 tocopherol Natural products 0.000 claims description 7
- 235000010384 tocopherol Nutrition 0.000 claims description 7
- 239000011732 tocopherol Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 7
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 6
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 6
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 6
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000005642 Oleic acid Substances 0.000 claims description 6
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 6
- 239000000787 lecithin Substances 0.000 claims description 6
- 235000010445 lecithin Nutrition 0.000 claims description 6
- 229940067606 lecithin Drugs 0.000 claims description 6
- 235000019198 oils Nutrition 0.000 claims description 6
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 6
- 235000012424 soybean oil Nutrition 0.000 claims description 6
- 239000003549 soybean oil Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 206010040047 Sepsis Diseases 0.000 claims description 4
- 210000004204 blood vessel Anatomy 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 210000003022 colostrum Anatomy 0.000 claims description 3
- 235000021277 colostrum Nutrition 0.000 claims description 3
- 210000003038 endothelium Anatomy 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 208000031729 Bacteremia Diseases 0.000 claims description 2
- 206010004053 Bacterial toxaemia Diseases 0.000 claims description 2
- 206010063837 Reperfusion injury Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 201000001421 hyperglycemia Diseases 0.000 claims description 2
- 239000004530 micro-emulsion Substances 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 241000717739 Boswellia sacra Species 0.000 claims 7
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 238000002481 ethanol extraction Methods 0.000 claims 2
- 239000012071 phase Substances 0.000 claims 2
- 208000013222 Toxemia Diseases 0.000 claims 1
- 239000003708 ampul Substances 0.000 claims 1
- 239000008346 aqueous phase Substances 0.000 claims 1
- 230000006866 deterioration Effects 0.000 claims 1
- 238000004945 emulsification Methods 0.000 claims 1
- 230000001804 emulsifying effect Effects 0.000 claims 1
- 201000005577 familial hyperlipidemia Diseases 0.000 claims 1
- 239000012467 final product Substances 0.000 claims 1
- 235000021313 oleic acid Nutrition 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 208000013223 septicemia Diseases 0.000 claims 1
- 239000000779 smoke Substances 0.000 claims 1
- 230000001954 sterilising effect Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 16
- 235000018062 Boswellia Nutrition 0.000 abstract description 8
- 241001608538 Boswellia Species 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 7
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 4
- 208000008589 Obesity Diseases 0.000 abstract description 3
- 235000020824 obesity Nutrition 0.000 abstract description 3
- 230000000391 smoking effect Effects 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 230000035622 drinking Effects 0.000 abstract description 2
- 230000004064 dysfunction Effects 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 1
- 239000011159 matrix material Substances 0.000 abstract 1
- 238000001556 precipitation Methods 0.000 abstract 1
- 230000008719 thickening Effects 0.000 abstract 1
- 201000008827 tuberculosis Diseases 0.000 abstract 1
- 240000007551 Boswellia serrata Species 0.000 description 23
- 235000003717 Boswellia sacra Nutrition 0.000 description 22
- 235000012035 Boswellia serrata Nutrition 0.000 description 22
- 241000700159 Rattus Species 0.000 description 17
- 210000003989 endothelium vascular Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 210000002889 endothelial cell Anatomy 0.000 description 7
- 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 6
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 5
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 5
- 229960002327 chloral hydrate Drugs 0.000 description 5
- 229960003072 epinephrine hydrochloride Drugs 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 238000010254 subcutaneous injection Methods 0.000 description 5
- 239000007929 subcutaneous injection Substances 0.000 description 5
- 108010049003 Fibrinogen Proteins 0.000 description 4
- 102000008946 Fibrinogen Human genes 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- XLIJUKVKOIMPKW-BTVCFUMJSA-N [O].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O Chemical compound [O].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XLIJUKVKOIMPKW-BTVCFUMJSA-N 0.000 description 4
- 229940012952 fibrinogen Drugs 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 210000003606 umbilical vein Anatomy 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 3
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 3
- 210000000702 aorta abdominal Anatomy 0.000 description 3
- 210000001715 carotid artery Anatomy 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- 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 3
- 238000010186 staining Methods 0.000 description 3
- 201000005665 thrombophilia Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 206010041956 Stasis syndrome Diseases 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 230000002785 anti-thrombosis Effects 0.000 description 2
- 208000005634 blind loop syndrome Diseases 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 238000001378 electrochemiluminescence detection Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000002398 materia medica Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- -1 polyoxyethylene Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- QAQJMLQRFWZOBN-UHFFFAOYSA-N 2-(3,4-dihydroxy-5-oxo-2,5-dihydrofuran-2-yl)-2-hydroxyethyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)C1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 206010007247 Carbuncle Diseases 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- 235000000072 L-ascorbyl-6-palmitate Nutrition 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical group C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Chemical class 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- JVFGXECLSQXABC-UHFFFAOYSA-N ac1l3obq Chemical compound O1C(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(O)C2O)C(COCC(O)C)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC2C(O)C(O)C1OC2COCC(C)O JVFGXECLSQXABC-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940125364 angiotensin receptor blocker Drugs 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000007957 coemulsifier Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- ATADHKWKHYVBTJ-UHFFFAOYSA-N hydron;4-[1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol;chloride Chemical compound Cl.CNCC(O)C1=CC=C(O)C(O)=C1 ATADHKWKHYVBTJ-UHFFFAOYSA-N 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000006207 intravenous dosage form Substances 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940057917 medium chain triglycerides Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 230000037257 muscle growth Effects 0.000 description 1
- 230000006715 negative regulation of smooth muscle cell proliferation Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920001223 polyethylene glycol Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了乳香提取物在制备预防和治疗血管内皮稳态失调药物中的应用。乳香酸提取物可用于制备预防肥胖、长期抽烟、喝酒等不良生活习惯及慢性应激所致的血管内皮细胞结构破坏和功能失调，治疗血管内皮损伤、基质沉淀所致的血管壁增厚和管腔狭窄性心血管疾病的药物，其具有活性强，毒副作用小，价格低廉的优点。
Description
技术领域
本发明涉及乳香提取物在制备预防和治疗血管内皮稳态失调药物中的应用，属于医药技术领域。
背景技术
血管内皮细胞是介于血流和血管壁组织之间的一层单核细胞，可通过分泌、内分泌、旁分泌三种途径分泌一系列NO, PGI2, ET-1等血管活性物质发挥调节血管紧张性、抗血栓形成、抑制平滑肌细胞增殖及血管壁炎症反应等功能。血管内皮稳态的破坏与生活环境及生活方式密切相关。肥胖、吸烟、不良生活习惯及慢性应激均可导致血管内皮受损。内皮细胞结构和功能的改变是多种心血管疾病的共同病理基础，高血压、冠心病等患者内皮结构和功能严重受损。目前，修复内皮损伤的主要药物包括钙离子拮抗剂、血管紧张素转换酶抑制剂和血管紧张素受体阻断剂。遗憾的是，频发的毒副作用限制了他们的应用。在血管内皮损伤和血管内皮稳态破坏的初期，尚未发生高血压或冠心病等严重器质性病变的情况下，尚缺乏有效且毒副作用小的治疗药物，因此研发维护血管内皮稳态的新药物是当前研究的前沿课题和热点领域。
乳香是橄榄科植物乳香树及同属植物的树干切口中渗出的坚硬胶状树脂。在我国，乳香之名始载于《名医别录》，后《本草拾遗》、《本草纲目》均有记载并沿用至今，认为其辛散温通，具有活血行气、通经止痛、消肿生肌、追毒之功效。现代药理学研究显示，乳香的主要成分有树脂（约含60～70%），树胶（约含27～35%），挥发油（约含3～8%）等，主治气血凝滞、心腹疼痛、痈疮肿毒、跌打损伤、痛经、产后瘀血刺痛，及具有镇痛、抗炎、抗菌、抗肿瘤等作用。乳香提取物由于其有效成分为水不溶性，目前乳香及其复方临床常用剂型为丸剂、胶囊剂、片剂、散剂、膏剂等口服或外用制剂，无静脉给药剂型，这使得药物吸收和生物利用度等大大降低，极大的限制了该药的临床应用。
发明内容
本发明的目的是提供乳香提取物在制备维持血管内皮稳态药物中的应用。
血管内皮稳态失调为肥胖、长期抽烟、喝酒等不了生活习惯及慢性应激所致的血管内皮细胞结构破坏和功能失调，包括高血压、高脂血症、动脉粥样硬化、高血糖、缺血再灌注损伤、血管成形术后再狭窄，以及菌血症、败血症、脓血症和毒血症引起的血管内皮损伤。
所述提取物为乳香乙醇提取物，其提取方法参照文献（P. R. SakuntalaDevi,K. Adilaxmamma, G. SrinivisaRao, ect. Safety Evaluation of AlcoholicExtract of Boswelliaovalifoliolata Stem-bark in Rats, 2012, Toxicol Int.,19(2): 115–120.）。使用时，将其制备成注射用乳剂、注射水针剂、注射油针剂、注射用粉针剂、注射用微乳或注射用脂质体。
注射剂按重量计，乳香提取物5-40%，表面活性剂10-45%，水介质添至100%，注射剂中还含有甘油三酯或甘油，助乳化剂脂肪酸、脂肪醇及其钠盐，胆酸、脱氧胆酸及其钠盐，抗氧化剂生育酚或L-抗坏血酸棕榈酸酯，其中甘油三酯包括植物油或中链甘油三酯，必要时可添加乙醇增溶。所述表面活性剂选自泊洛沙姆系列、植物磷脂、动物磷脂、合成磷脂、丙二醇、脂肪酸甘油酯、solutolHS15、labrosol、吐温类、聚氧乙烯脂肪酸酯、聚乙二醇衍生物系列、羟丙基β-环糊精、羟丙基γ-环糊精。
一种较优的配方是，按重量计，乳香提取物10-30%、乙醇1-5%、卵磷脂10-30%、精制大豆油5-25%、油酸0.5-6.5%、生育酚0.01-1.0%、注射用生理盐水添至100%。
本发明的优点在于：1) 本发明属于中药制剂，成分纯天然，毒副作用低；2)本发明能有效预防和治疗血管内皮损伤；3)本发明能有效延缓进行性心脑血管病变的发展；4)本发明注射剂生物利用度高。5)本品制备工艺简单，易于规范化生产。
附图说明
图1为乳香乳剂对大鼠血管内皮的作用。数据显示，模型组可见明显的血管内皮损伤，乳香乳剂可有效预防和对抗血管内皮损伤；
图2为乳香乳剂对血管内皮释放NO和cGMP的调节作用。数据显示，模型组血浆中NO含量明显降低，乳香乳剂可有效升高血浆中NO和 cGMP含量，数据均表示为mean±SD (n=6), #P<0.05 vs 模型组；
图3为乳香乳剂对内皮细胞一氧化氮合酶（eNOS）的作用。数据显示，模型组血管内皮细胞中磷酸化的eNOS表达显著降低，乳香乳剂可有效增加eNOS在血管内皮细胞中的表达；
图4为乳香乳剂对脐静脉内皮细胞（HUVEC）的作用。数据显示，乳香乳剂有效抑制氧糖剥夺（OGD）诱导的HUVEC死亡，#P<0.05 vs 氧糖剥夺组。
具体实施方式
乳香醇提取物乳剂的制备：乳香提取物10-30%、乙醇1-5%、卵磷脂10-30%、精致大豆油5-25%、油酸0.5-6.5%、生育酚0.01-1.0%、注射用生理盐水添至100%。
上述注射用乳香提取物制备方法为：在10-30%乳香提取物中加入1-5%乙醇、5-25%精制大豆油、0.01-1.0%生育酚和0.5-6.5%油酸，并快速搅拌制成油相；将10-30%卵磷脂与注射用生理盐水配制成水相，油水两相混合，高速搅拌制成初乳；加之注射用生理盐水至100%，调节pH至5.0-7.0，至高压乳匀机中，反复乳化至乳滴平均粒径≤0.5μm；取上述乳剂过滤后，充氮气灌装，灭菌即得。
本发明乳香提取物可用于防治血液高凝状态，并采用以下方法进行验证乳香乳剂改善血瘀证大鼠高凝状态，保护血管内皮，调节血管活性的作用：雄性SD大鼠，体重220-280g, ，乳香乳剂静脉注射（3各剂量水平200，100，50 mg/kg），给药3天后，皮下注射盐酸肾上腺素0.8mgl/kg，间隔4 h再注射一次。首次注射盐酸肾上腺索后2h后，进行1次寒冷刺激，将大鼠在冰水浴中（0-2℃）浸泡5 min，从而造成大鼠急性血瘀证模型。最后一次给药30分钟内，用3.5%水合氯醛麻醉，经腹主动脉取血2ml，以3.8%的枸橼酸钠抗凝，2500r/min离心15min，取血浆测定凝血酶原时间（PT）、活化部分凝血酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（FIB）、NO和cGMP的含量。取颈动脉，置于10%福尔马林液中固定，石蜡包埋，切片，行苏木素-伊红（HE）染色。
本发明乳香提取物可用于防治血管内皮损伤，并采用以下方法进行验证乳香乳剂保护血管内皮的作用：脐静脉内皮细胞HUVEC培养至70-80%，弃去细胞培养液，用PBS清洗3次，更换培养液为PBS，然后放入含95 %N2+5 % CO2的37℃孵箱中120 min，氧糖剥夺后，更换PBS为DMEM（10%FBS）培养液，放入37℃, 5%CO2孵箱，24 h后检测HUVEC的存活率。
实施例1
取乳香提取物200mg，加入无水乙醇100μl，精致大豆油200mg，油酸80mg，生育酚1mg，于50℃下高速搅拌使其溶解均匀，制成油相；卵磷脂200mg溶于适量注射用生理盐水中，于50℃下高速搅拌使其溶解均匀制成水相；油水两相混合于60℃高速搅拌制成初乳；加之注射用生理盐水至2mL，调节pH至5.0-7.0，至高压乳匀机中，反复乳化至乳滴平均粒径≤0.5μm。取上述乳剂过滤后，充氮气灌装，灭菌即得。
实施例2
将上述乳香乳剂置于室温、高温和光照，分别考察0天，5天和10天的性状、pH值、不溶性微粒和可见异物。结果见表1：制剂稳定。
实施例3 乳香提取物对血瘀证大鼠凝血功能的作用
SD大鼠40只，体重220-280g，购自第四军医大学动物实验中心。动物分笼饲养（环境温度24℃，湿度60-70%），大鼠随机分为5组：（1）对照组；（2）模型组；（3）模型给药组（高中低剂量的乳香乳剂静脉注射），每12小时给药1次，连续给药7次，5次给药后造模，除空白组外给予皮下注射盐酸肾上腺素（0.8mg·kg-1）2次，间隔4小时，中间给予冰水（0-2℃）刺激，最后一次给药30分钟内，用3.5%水合氯醛麻醉，经腹主动脉取血2ml，以3.8%的枸橼酸钠抗凝，2500r/min离心15min，取血浆测定PT、APTT、TT、FIB。结果见表2，表中数据均表示为mean±SD (n=6), ##: 与空白组相比p<0.01；#:与空白组相比p<0.05；**:与模型组相比p<0.01；*:与模型组相比p<0.05。数据显示，与正常组相比，模型组TT、PT、APTT均显著缩短，FIB显著升高（P<0.01），说明造模成功。与模型组相比高中低剂量三个组的能够延长TT、PT、APTT（P<0.01），证实乳香乳剂具有显著的改善血液高凝状态，促进血液循环的作用。
实施例4 乳香提取物对大鼠血管内皮的保护作用
SD大鼠24只，体重220-280g，购自第四军医大学动物实验中心。动物分笼饲养（环境温度24℃，湿度60-70%），大鼠随机分为5组：（1）对照组；（2）模型组；（3）模型给药组（乳香乳剂静脉注射），每12小时给药1次，连续给药7次，5次给药后造模，除空白组外给予皮下注射盐酸肾上腺素（0.8mg·kg-1）2次，间隔4小时，中间给予冰水（0-2℃）刺激，最后一次给药30分钟内，用3.5%水合氯醛麻醉，取颈动脉，置于10%福尔马林液中固定，石蜡包埋，切片，行苏木素-伊红（HE）染色，结果（见图1）：与正常组相比，模型组的血管内皮受损，血管内皮细胞部分从血管壁脱落，乳香乳剂可明显保护血管内皮，改善血管内皮的损伤状态，维持血管内皮结构和功能的完整性。
实施例5 乳香提取物对血管内皮释放NO和cGMP的作用
SD大鼠40只，体重220-280g，购自第四军医大学动物实验中心。动物分笼饲养（环境温度24℃，湿度60-70%），大鼠随机分为5组：（1）空白对照组；（2）模型组；（3）模型给药组（高中低剂量的乳香乳剂静脉注射），每12小时给药1次，连续给药7次，5次给药后造模，除空白对照组外给予皮下注射盐酸肾上腺素（0.8mg·kg-1）2次，间隔4小时，中间给予冰水（0-2℃）刺激，最后一次给药30分钟内，用3.5%水合氯醛麻醉，经腹主动脉取血2mL，以3.8%的枸橼酸钠抗凝，2500r/min离心15min，取血浆测定NO和cGMP的含量。结果（见图2）。
实施例6 乳香提取物对内皮细胞一氧化氮合酶（eNOS）的作用
SD大鼠24只，体重220-280g，购自第四军医大学动物实验中心。动物分笼饲养（环境温度24℃，湿度60-70%），大鼠随机分为5组：（1）对照组；（2）模型组；（3）模型给药组（乳香乳剂静脉注射），每12小时给药1次，连续给药7次，5次给药后造模，除空白组外给予皮下注射盐酸肾上腺素（0.8mg·kg-1）2次，间隔4小时，中间给予冰水（0-2℃）刺激，最后一次给药30分钟内，用3.5%水合氯醛麻醉，取颈动脉匀浆的蛋白样品进行SDS-PAGE电泳(分离胶浓度为8％，积层胶浓度为4％)，转膜，封闭过夜，1：1000稀释的抗p-NOS 和T-NOS (Santa Cruz公司) , 4℃杂交过夜，1：2 000稀释的辣根过氧化酶标记的羊抗兔二抗(a Rb IgG／HRP，中山生物公司)交联物室温反应1h，增强化学发光试剂(ECL，Santa Cruz公司)进行显影，经电子计算机灰度扫描处理（见图3）：
实施例7 乳香提取物对HUVEC 脐静脉内皮细胞的保护作用
脐静脉内皮细胞HUVEC培养至70-80%，分为空白对照组，氧糖剥夺（OGD）组，氧糖剥夺（OGD）组给药组，其中氧糖剥夺（OGD）组给药组给予乳香乳剂预处理12小时，3组均进行OGD处理。弃去细胞培养液，用PBS清洗3次，更换培养液为PBS，然后放入含95 %N2+5 % CO2的37℃孵箱中120 min，更换PBS为DMEM（10%FBS）培养液，放入37℃, 5%CO2孵箱，24 h后采用台盼蓝染色检测HUVEC的存活率。用Hanks液配制0.1%台盼蓝溶液。用0.5% 胰蛋白酶 ：0.2% EDTA = 1：1混合液来消化培养的贴壁细胞，制成细胞混悬液后加入台盼蓝染色3-5min, 取一滴染色过的细胞悬液置玻片上，加盖玻片后进行细胞计数。死亡的细胞着浅蓝色并膨大，无光泽。活细胞不着色并保持正常形态，有光泽， 计数1000个细胞中的活细胞和死细胞数目，可按公式计算出细胞活率（细胞活率（%）=未染色的细胞数/观察的细胞总数×100）（见图4）。
实施例1-7的结果表明：乳香提取物所制备的乳剂可通过增强血管内皮细胞中一氧化氮合酶的活性，促进NO和cGMP的表达，维护血管内皮细胞的结构和功能，抗血栓形成，抑制血管壁炎症，维护血管内皮的稳态和血管舒缩活性，可用于预防和治疗多种心脑血管疾病：如高血压、高血脂、动脉粥样硬化等，作为血管内皮保护药物，维护血管内皮稳态的制剂具有良好的开发前景。
Claims (6)
1.乳香提取物在制备预防和治疗血管内皮稳态失调药物中的应用。
2.根据权利要求1所述的应用，其特征在于：所述血管内皮稳态失调为肥胖、长期抽烟、喝酒等不良生活习惯及慢性应激所致的血管内皮细胞结构破坏和功能失调，以及高血压、高脂血症、动脉粥样硬化、高血糖、缺血再灌注损伤、血管成形术后再狭窄，以及菌血症、败血症、脓血症和毒血症引起的血管内皮损伤。
3.根据权利要求1或2所述的应用，其特征在于：所述乳香提取物为乳香乙醇提取物。
4.根据权利要求3所述应用，其特征在于：所述的乳香乙醇提取物制备成注射用乳剂、注射水针剂、注射油针剂、注射用粉针剂、注射用微乳或注射用脂质体。
5.根据权利要求4所述应用，其特征在于：按重量计，乳香提取物10-30%、乙醇1-5%、卵磷脂10-30%、精制大豆油5-25%、油酸0.5-6.5%、生育酚0.01-1.0%、注射用生理盐水添至100%。
6.根据权利要求5所述应用，其特征在于注射用乳香提取物制备方法为：在乳香提取物中加入乙醇、精制大豆油、生育酚和油酸，并快速搅拌制成油相；将卵磷脂与注射用生理盐水配制成水相，油水两相混合，高速搅拌制成初乳；加之注射用生理盐水至100%，调节pH至5.0-7.0，至高压乳匀机中，反复乳化至乳滴平均粒径≤0.5μm；取上述乳剂过滤后，充氮气灌装，灭菌即得。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410843006.5A CN104546982A (zh) | 2014-12-31 | 2014-12-31 | 乳香提取物在制备维持血管内皮稳态药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410843006.5A CN104546982A (zh) | 2014-12-31 | 2014-12-31 | 乳香提取物在制备维持血管内皮稳态药物中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104546982A true CN104546982A (zh) | 2015-04-29 |
Family
ID=53064754
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410843006.5A Pending CN104546982A (zh) | 2014-12-31 | 2014-12-31 | 乳香提取物在制备维持血管内皮稳态药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104546982A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110269824A (zh) * | 2019-07-19 | 2019-09-24 | 安徽宝利行香料有限公司 | 乳香提取物在日用品及洗涤用品中的应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1954825A (zh) * | 2005-10-26 | 2007-05-02 | 河北以岭医药研究院有限公司 | 超微通心络中药组合物及其新用途 |
| CN101590123A (zh) * | 2008-05-27 | 2009-12-02 | 河北以岭医药研究院有限公司 | 一种中药组合物在制备保护损伤的血管内皮的药物中的应用 |
| CN102711781A (zh) * | 2010-02-15 | 2012-10-03 | 莱拉营养食品有限公司 | 一种新型的乳香低极性树胶脂提取物及其协同增效的组合物 |
| CN103393740A (zh) * | 2013-07-31 | 2013-11-20 | 中国人民解放军第四军医大学 | 乳香提取物在防治心脑血管或肝肾损伤中应用 |
-
2014
- 2014-12-31 CN CN201410843006.5A patent/CN104546982A/zh active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1954825A (zh) * | 2005-10-26 | 2007-05-02 | 河北以岭医药研究院有限公司 | 超微通心络中药组合物及其新用途 |
| CN101590123A (zh) * | 2008-05-27 | 2009-12-02 | 河北以岭医药研究院有限公司 | 一种中药组合物在制备保护损伤的血管内皮的药物中的应用 |
| CN102711781A (zh) * | 2010-02-15 | 2012-10-03 | 莱拉营养食品有限公司 | 一种新型的乳香低极性树胶脂提取物及其协同增效的组合物 |
| CN103393740A (zh) * | 2013-07-31 | 2013-11-20 | 中国人民解放军第四军医大学 | 乳香提取物在防治心脑血管或肝肾损伤中应用 |
Non-Patent Citations (2)
| Title |
|---|
| 王建新: "《化妆品植物原料手册》", 30 June 2009, 化学工业出版社 * |
| 王明明 等: "羟基红花黄色素A联用β-乳香酸对血瘀证模型大鼠凝血功能、NO、cGMP的影响", 《中国药房》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110269824A (zh) * | 2019-07-19 | 2019-09-24 | 安徽宝利行香料有限公司 | 乳香提取物在日用品及洗涤用品中的应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101145248B1 (ko) | 신생혈관형성 억제용 한약 조성물 | |
| CN113274343B (zh) | 多元醇作为助溶剂在秋水仙碱外用组合物中的应用 | |
| CN103610778B (zh) | 抗鸡热应激的中药制剂及其制备方法 | |
| Mao et al. | Isorhamnetin improves diabetes-induced erectile dysfunction in rats through activation of the Pi3k/Akt/Enos signaling pathway | |
| CN111888331B (zh) | 一种榄香烯卡巴他赛复方柔性乳剂及其制备方法 | |
| Giagulli et al. | The pathogenic role of the immune system in erectile dysfunction and Peyronie’s disease: focusing on immunopathophysiology and potential therapeutic strategies | |
| Xu et al. | Fabrication of a protein-dextran conjugates formed oral nanoemulsion and its application to deliver the essential oil from Alpinia zerumbet Fructus | |
| CN104546982A (zh) | 乳香提取物在制备维持血管内皮稳态药物中的应用 | |
| CN107126418B (zh) | 供注射用双氯芬酸钠药物组合物及其制备方法 | |
| CN105311622B (zh) | 一种治疗疼痛的联合用药物及其制剂、制备方法 | |
| JP7612025B2 (ja) | 敗血症を治療するための薬物組成物及びその使用 | |
| Gostyńska et al. | Natural bioactive compounds–the promising candidates for the treatment of intestinal failure-associated liver disease | |
| CN115590885A (zh) | 人脐带间充质干细胞外泌体在防治动脉粥样硬化药物中的应用 | |
| CN105687178B (zh) | 丹酚酸a单独或多药联合在制备治疗肾病综合症药物中的应用 | |
| CN107569453A (zh) | 一种含蛋黄油具有修复冻烫伤及湿疹的抗衰小黄乳制备方法和应用 | |
| Xie et al. | PH-sensitive BSA-modified resveratrol micelles targeting macrophages alleviate symptoms of rheumatoid arthritis | |
| Enechi et al. | Phytochemical Composition and Anti-Inflammatory Potential of Flavonoid-Rich Fraction of Erythrina senegalensis DC (Fabaceae) Leaf. | |
| CN109260149B (zh) | 一种含有γ-生育三烯酚的纳米乳液及其制备方法和用途 | |
| CN100525753C (zh) | 辅酶q10亚微乳注射液及制备方法 | |
| WO2024032050A1 (zh) | 可自乳化的多西他赛注射用组合物及其制备方法 | |
| CN113057940B (zh) | 1,8-桉叶油素乳剂及其制备方法 | |
| CN103816118A (zh) | 一种多烯磷脂酰胆碱注射用组合物及其制备方法 | |
| US20230405070A1 (en) | Plectranthus amboinicus extract for use in inhibiting immune responses | |
| CN118987002A (zh) | 一种治疗常染色体显性多囊肾病的药物组合物及制备方法 | |
| CN102091326B (zh) | 治疗因肛门皮下的静脉丛发生扩大或曲张所引发的痔类疾病的经皮给药制剂及制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into 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: 20150429 |