CN103446057B - Oral curcumin nano-granule and preparation method thereof - Google Patents
Oral curcumin nano-granule and preparation method thereof Download PDFInfo
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- CN103446057B CN103446057B CN201310399929.1A CN201310399929A CN103446057B CN 103446057 B CN103446057 B CN 103446057B CN 201310399929 A CN201310399929 A CN 201310399929A CN 103446057 B CN103446057 B CN 103446057B
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- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 title claims abstract description 86
- 229940109262 curcumin Drugs 0.000 title claims abstract description 43
- 235000012754 curcumin Nutrition 0.000 title claims abstract description 43
- 239000004148 curcumin Substances 0.000 title claims abstract description 43
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000008187 granular material Substances 0.000 title claims abstract description 15
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229960002897 heparin Drugs 0.000 claims abstract description 17
- 229920000669 heparin Polymers 0.000 claims abstract description 17
- WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic 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)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000002105 nanoparticle Substances 0.000 claims description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 230000004913 activation Effects 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 239000012153 distilled water Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 239000008367 deionised water Substances 0.000 claims description 3
- 229910021641 deionized water Inorganic materials 0.000 claims description 3
- 238000001338 self-assembly Methods 0.000 claims description 3
- SAQSTQBVENFSKT-UHFFFAOYSA-M TCA-sodium Chemical class [Na+].[O-]C(=O)C(Cl)(Cl)Cl SAQSTQBVENFSKT-UHFFFAOYSA-M 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- 238000002390 rotary evaporation Methods 0.000 claims description 2
- QRNZMFDCKKEPSX-UHFFFAOYSA-N 4-mercapto-4-methylpentan-2-one Chemical compound CC(=O)CC(C)(C)S QRNZMFDCKKEPSX-UHFFFAOYSA-N 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 108091022863 bile acid binding Proteins 0.000 abstract description 2
- 102000030904 bile acid binding Human genes 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 230000003993 interaction Effects 0.000 abstract description 2
- 230000003527 anti-angiogenesis Effects 0.000 abstract 1
- 230000002785 anti-thrombosis Effects 0.000 abstract 1
- 230000007547 defect Effects 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 210000000813 small intestine Anatomy 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 5
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].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)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 5
- 239000003814 drug Substances 0.000 description 4
- QYZPDCGWIJYZMN-ZBFHGGJFSA-N n-[3-(n'-hydroxycarboxamido)-2-(2-methylpropyl)-propanoyl]-o-tyrosine-n-methylamide Chemical compound ONC(=O)C[C@@H](CC(C)C)C(=O)N[C@H](C(=O)NC)CC1=CC=C(OC)C=C1 QYZPDCGWIJYZMN-ZBFHGGJFSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical class CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 244000164480 Curcuma aromatica Species 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- -1 average 5000kDa) Chemical compound 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002389 essential drug Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
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- 238000000034 method Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940044652 phenolsulfonate Drugs 0.000 description 1
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Abstract
The invention belongs to the technical field of pharmaceutical preparation and particularly relates to an oral curcumin nano-granule and a preparation method thereof. The nano-granule is prepared by self-assembling a ternary conjugated compound which is obtained by connecting taurocholic acid, heparin and curcumin through amido bonds, the curcumin is a core of the nano-granule, and the hydrophilic taurocholic acid is on the surface of the nano-granule. The oral curcumin nano-granule overcomes the poor water solubility of curcumin, the absorption of the nano-granule can be enhanced by utilizing the interaction of taurocholic acid and bile acid transporter of small intestine, the defect that the bioavailability of the oral curcumin is low can be overcome, and the heparin also has anti-thrombosis and anti-angiogenesis effect.
Description
One, technical field
The invention belongs to technical field of medicine, be specifically related to a kind of oral curcumin nano-granule and preparation method thereof
Two, background technology
Curcumin (curcumin) is the fat-soluble phenol sulfonate of one extracted from the rhizome of Zingiberaceae curcuma Rhizoma Curcumae Longae, Rhizoma Curcumae, Radix Curcumae etc., there is antiinflammatory, antioxidation, the pharmacological action such as anticancer, the various diseases symptoms such as cancer, diabetes, metabolic disease, autoimmune disease, atherosclerosis, arthritis, apoplexy, peripheral neurophaty, enteritis and cerebral trauma can be improved.But due to curcumin poorly water-soluble, easily oxidized in vitro, and there is no the good pharmaceutical dosage form of stability at present, administration difficulty.The curcumin preparation gone on the market at present or report mainly contains: emulsifying agent (200510042547.9,200780008293.6,200910101327.7,201010214085.5), solid dispersion (200510035060.8), liposome (200610026576.0,200810155819.X, 200910009097.1,201010561666.6), nanoparticle (200610125179.9,200810159648.8,200910201403.1,201010528014.2), slow releasing agent (200610154913.4), injection (200310116734.8).The conventional route of administration of these preparations has oral, intramuscular injection and intravenous injection, and wherein intramuscular injection and intravenous injection need professional to complete, and are unwell to autonomous medication, although and traditional oral administration is easy to use, often bioavailability is lower.Therefore, there is a need in the field to provide a kind of safe, effective, easy to use, curcumin preparation that bioavailability is high.
Three, summary of the invention
Problem to be solved by this invention is to provide a kind of oral curcumin nano-granule and preparation method thereof.
Nanoparticle of the present invention be taurocholic acid with heparin, curcumin by being connected, obtain a kind of ternary conjugated compound, this compound can be self-assembled into nanoparticle.
The essential drugs that oral curcumin nano-granule of the present invention needs in the process of preparation: curcumin, heparin (heparin, average 5000kDa), Taurocholic acid sodium salt (TCA).
Some chemical reagent that oral curcumin nano-granule described in the present invention is used in preparation process: DMF (DMF), triethylamine (TEA), 4-chloroformate nitrophenyl ester (4-NPC), ethanol (EtOH), deionized water, 4-methyl morpholine (4-MMP), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimides (EDC), N-hydroxysuccinimide (NHS), ethylenediamine (EDA)
The preparation method of the oral curcumin nano-granule in the present invention, prepares: the activation of (1) taurocholic acid and the connection with heparin according to the following steps; (2) activation of curcumin; (3) heparin-curcumin-taurocholic acid conjugate and HCTA is synthesized; (4) preparation of HCTA nanoparticle.
The present invention compared with prior art its beneficial effect is: oral administration nanometer grain overcomes curcumin poorly water-soluble; and utilize the interaction of bile acid transporter of taurocholic acid and small intestinal; increase the absorption of medicine; the shortcoming that oral curcumin bioavailability is low can be overcome; there is advantages such as increasing drug absorption, zest is little, easy to use, dosage is accurate; and heparin also has the effect of antithrombus formation and angiogenesis inhibitor, it is the form of administration that compliance that a kind of safe, effective, patient takes like a shot is high.
Four, accompanying drawing explanation
Fig. 1 is the picture of HCTA nanoparticle under scanning electron microscope
Fig. 2 is the grain size distribution of HCTA nanoparticle
Five, detailed description of the invention
Preparation process:
1, the activation of taurocholic acid and the connection with heparin
(1) the TCA sodium salt of 1mol is dissolved in the DMF of 5ml0 DEG C, then adds 5molTEA and 4mol4-NPC, reacts 1h with this understanding, then stirred at ambient temperature 5h.Reaction solution is extracted by centrifugal and separatory funnel (ethanol 20ml, deionized water 20ml), in triplicate.The solution be separated is placed in rotary evaporator evaporation of organic solvent, and last lyophilization 24h, obtains TCA-NPC powder.1mol TCA-NPC is dissolved in 5ml DMF, adds the 4-MMP of 3mol, at 50 DEG C, react 2h, then dropwise add 50mol EDA, then stirred at ambient temperature 20h, crystalline portion filters and carries out drying in vacuum desiccator, obtains TCA-NH2.
(2) 1mol heparin to be dissolved in distilled water and to add hydrochloric acid solution adjust pH condition in the scope of 5.5-6, add 7mol EDC, stir 10min, then 8mol NHS is added, stir 40min, TCA-NH2 joins the rate of charge control TCA of stirred at ambient temperature 12h, TCA-NH2 in solution and the connection amount of heparin.Finally, dialysed by this solution, 36h, to remove free EDC and NHS, obtains Heparin-TCA (HTA)
2, the activation of curcumin Curcumin
The DMSO solution of curcumin adds TEA and 4-NPC stirred at ambient temperature, by TEA and 4-NPC that methanol and hexane solution extraction removing dissociate after 12h, in triplicate.MMP is joined in the curcumin methanol solution containing activation, stirred at ambient temperature 2h, then add EDA and continue to stir 12h.Normal hexane is added, in order to extract away free MMP and EDA in reaction solution.By this solution, rotary evaporation 2h, removing normal hexane.Obtain curcumin-NH
2
3, heparin-curcumin-taurocholic acid conjugate (HCTA) is synthesized
1mol HTA is dissolved in distilled water, adds 8mol EDC and 10mol NHS, stirs 1h.Then by curcumin-NH
2add reaction solution, stirred at ambient temperature 12h.Curcumin-NH
2the connection amount of charge ratio control curcumin and HTA.Reaction solution is dialysed, with the curcumin removing free EDC with NHS, be not connected.Finally, whole solution is dry at freezer dryer, obtains the HCTA conjugate of powder type.
4, the preparation of nanoparticle
HCTA, this ternary biomolecule conjugate water soluble self assembly forms nano-particle, and the nanoparticle curcumin of formation is positioned at core, and taurocholic acid is distributed in the surface of nanoparticle.And the ratio of the particle diameter of nanoparticle and Heparin and TCA, HTA and curcumin is closely related.
5, the sign of nanoparticle
The different coupling ratio of table 1 heparin, sodium taurocholate and curcumin is relevant to size
Claims (2)
1. an oral curcumin nano-granule, is characterized in that by mean molecule quantity be the heparin of 5000kDa, curcumin, and taurocholic acid is formed with a kind of conjugate self assembly be linked in sequence of curcumin-heparin-taurocholic acid by amido link.
2. the preparation method of a kind of oral curcumin nano-granule according to claim 1, is characterized in that being made up of following steps:
(1). the activation of taurocholic acid and the connection with heparin:
(A) the TCA sodium salt of 1mol is dissolved in the DMF of 5ml 0 DEG C, then 5molTEA and 4mol 4-NPC is added, react 1h with this understanding, then stirred at ambient temperature 5h, reaction solution is by centrifugal and separatory funnel wherein ethanol 20ml, deionized water 20ml, extract, in triplicate, the solution be separated is placed in rotary evaporator evaporation of organic solvent, last lyophilization 24h, obtain TCA-NPC powder, 1mol TCA-NPC is dissolved in 5ml DMF, add the 4-MMP of 3mol, 2h is reacted at 50 DEG C, then 50mol EDA is dropwise added, then stirred at ambient temperature 20h, crystalline portion filters and carries out drying in vacuum desiccator, obtain TCA-NH
2,
(B) 1mol mean molecule quantity is that the heparin of 5000kDa to be dissolved in distilled water and to add hydrochloric acid solution adjust pH condition in the scope of 5.5-6, adds 7mol EDC, stirs 10min, then add 8mol NHS, stir 40min, TCA-NH
2join stirred at ambient temperature 12h, TCA-NH in solution
2rate of charge control TCA and the connection amount of heparin, finally, dialysed by this solution, 36h, to remove free EDC and NHS, obtains Heparin-TCA and HTA;
(2). the activation of curcumin Curcumin:
The DMSO solution of curcumin adds TEA and 4-NPC stirred at ambient temperature, by TEA and 4-NPC that methanol and hexane solution extraction removing dissociate after 12h, in triplicate, MMP is joined in the curcumin methanol solution containing activation, stirred at ambient temperature 2h, then add EDA to continue to stir 12h, in reaction solution, add normal hexane, in order to extract away free MMP and EDA, by this solution, rotary evaporation 2h, removing normal hexane, obtains curcumin-NH
2;
(3). synthesis heparin-curcumin-taurocholic acid conjugate and HCTA:
1mol HTA is dissolved in distilled water, adds 8mol EDC and 10mol NHS, stirs 1h, then by curcumin-NH
2add reaction solution, stirred at ambient temperature 12h, curcumin-NH
2the connection amount of charge ratio control curcumin and HTA, dialyses reaction solution, and with the curcumin removing free EDC with NHS, be not connected, finally, whole solution is dry at freezer dryer, obtains the HCTA conjugate of powder type;
(4) preparation of .HCTA nanoparticle:
The water-soluble self assembly of HCTA ternary biomolecule conjugate forms nano-particle; and the particle diameter of nanoparticle and Heparin and TCA; the ratio of HTA with curcumin is closely related, and the nanoparticle curcumin of formation is positioned at core, and taurocholic acid is distributed in the surface of nanoparticle.
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| CN107519544A (en) * | 2017-08-28 | 2017-12-29 | 武汉杨森生物技术有限公司 | Compound anticoagulant heparin coating microballoon and preparation method and application |
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| CN105434407B (en) * | 2015-12-09 | 2018-06-19 | 中国药科大学 | A kind of curcumin nano-lipid carrier of high bioavilability |
| CN108379230A (en) * | 2018-03-28 | 2018-08-10 | 北京凯宾鸿生物医药科技有限公司 | A kind of oral granule of bile acid modification |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101711740A (en) * | 2009-12-18 | 2010-05-26 | 苏州大学 | Method for preparing targeted curcumin nanoparticles for treating ulcerative colitis |
| CN102988999A (en) * | 2012-05-09 | 2013-03-27 | 中国药科大学 | Curcumin-polysaccharide conjugate as well as preparation method and application thereof |
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| CN101711740A (en) * | 2009-12-18 | 2010-05-26 | 苏州大学 | Method for preparing targeted curcumin nanoparticles for treating ulcerative colitis |
| CN102988999A (en) * | 2012-05-09 | 2013-03-27 | 中国药科大学 | Curcumin-polysaccharide conjugate as well as preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 姜黄素前药的研究进展;涂永元等;《有机化学》;20121231;第32卷(第5期);852-859 * |
| 姜黄素纳米制剂的研究进展;张玉潜等;《中国医院药学杂志》;20130228;第33卷(第4期);316-319 * |
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| CN107519544A (en) * | 2017-08-28 | 2017-12-29 | 武汉杨森生物技术有限公司 | Compound anticoagulant heparin coating microballoon and preparation method and application |
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