CN101068556B - Pilose antler nano-products containing enriched insulin-like growth factor and producing method thereof - Google Patents
Pilose antler nano-products containing enriched insulin-like growth factor and producing method thereof Download PDFInfo
- Publication number
- CN101068556B CN101068556B CN2006800012623A CN200680001262A CN101068556B CN 101068556 B CN101068556 B CN 101068556B CN 2006800012623 A CN2006800012623 A CN 2006800012623A CN 200680001262 A CN200680001262 A CN 200680001262A CN 101068556 B CN101068556 B CN 101068556B
- Authority
- CN
- China
- Prior art keywords
- goods
- nanorize
- extract
- cornu cervi
- cervi pantotrichum
- 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.)
- Expired - Fee Related
Links
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 title claims abstract description 61
- 210000003056 antler Anatomy 0.000 title abstract description 6
- 102000013275 Somatomedins Human genes 0.000 title abstract 4
- 238000000034 method Methods 0.000 title description 18
- 238000002360 preparation method Methods 0.000 claims abstract description 37
- 239000003814 drug Substances 0.000 claims abstract description 17
- 239000002537 cosmetic Substances 0.000 claims abstract description 9
- 239000000284 extract Substances 0.000 claims description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 37
- 239000002088 nanocapsule Substances 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 17
- 229920001661 Chitosan Polymers 0.000 claims description 16
- 239000002775 capsule Substances 0.000 claims description 16
- 238000010298 pulverizing process Methods 0.000 claims description 13
- 239000002245 particle Substances 0.000 claims description 11
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 238000004108 freeze drying Methods 0.000 claims description 7
- 235000013402 health food Nutrition 0.000 claims description 7
- 239000007924 injection Substances 0.000 claims description 7
- 238000002347 injection Methods 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 230000023852 carbohydrate metabolic process Effects 0.000 claims description 5
- 235000021256 carbohydrate metabolism Nutrition 0.000 claims description 5
- 238000005507 spraying Methods 0.000 claims description 5
- 230000004663 cell proliferation Effects 0.000 claims description 3
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims 4
- 230000036541 health Effects 0.000 abstract description 6
- 235000013305 food Nutrition 0.000 abstract description 5
- 102000014429 Insulin-like growth factor Human genes 0.000 description 53
- 239000000047 product Substances 0.000 description 38
- 229920000642 polymer Polymers 0.000 description 18
- 230000000694 effects Effects 0.000 description 16
- 239000012528 membrane Substances 0.000 description 16
- 239000000725 suspension Substances 0.000 description 15
- 239000008367 deionised water Substances 0.000 description 14
- 229910021641 deionized water Inorganic materials 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 238000004090 dissolution Methods 0.000 description 10
- 239000012530 fluid Substances 0.000 description 10
- 238000000108 ultra-filtration Methods 0.000 description 10
- 239000000178 monomer Substances 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 235000018102 proteins Nutrition 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- 238000001514 detection method Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000004321 preservation Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241001597008 Nomeidae Species 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- -1 alkyl cyanoacrylate Chemical compound 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 229920005615 natural polymer Polymers 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 229920001610 polycaprolactone Polymers 0.000 description 4
- 239000004632 polycaprolactone Substances 0.000 description 4
- 229920000728 polyester Polymers 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 229920001059 synthetic polymer Polymers 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 229920001503 Glucan Polymers 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 108010019160 Pancreatin Proteins 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 229920005601 base polymer Polymers 0.000 description 3
- 238000006065 biodegradation reaction Methods 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 238000004925 denaturation Methods 0.000 description 3
- 230000036425 denaturation Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 230000007515 enzymatic degradation Effects 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 238000002386 leaching Methods 0.000 description 3
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229940055695 pancreatin Drugs 0.000 description 3
- 239000004626 polylactic acid Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 229920001651 Cyanoacrylate Polymers 0.000 description 2
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000002265 Human Growth Hormone Human genes 0.000 description 2
- 108010000521 Human Growth Hormone Proteins 0.000 description 2
- 239000000854 Human Growth Hormone Substances 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000010775 animal oil Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000009514 concussion Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 210000002249 digestive system Anatomy 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 238000000935 solvent evaporation Methods 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000009210 therapy by ultrasound Methods 0.000 description 2
- 230000008467 tissue growth Effects 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 241000282994 Cervidae Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920000832 Cutin Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 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
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor 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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003796 beauty Effects 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
- 235000013361 beverage Nutrition 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 108010089807 chitosanase Proteins 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 210000003027 ear inner Anatomy 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000010327 methods by industry Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003232 mucoadhesive effect Effects 0.000 description 1
- 239000002114 nanocomposite Substances 0.000 description 1
- 239000005445 natural material Substances 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
- 238000011022 operating instruction Methods 0.000 description 1
- 239000013588 oral product Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000003208 petroleum 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
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- PRXRUNOAOLTIEF-WUOFIQDXSA-N sorbitan trioleate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C\CCCCCCCC)C1OCC(O)C1OC(=O)CCCCCCC\C=C\CCCCCCCC PRXRUNOAOLTIEF-WUOFIQDXSA-N 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/30—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Optics & Photonics (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Physics & Mathematics (AREA)
- Nanotechnology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Hematology (AREA)
- Virology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
Abstract
The invention relates to an antler extractive nanometer product which is rich with insulin-like growth factor (IGF-1) and the preparation method thereof. The content of the IGF-1 in the extractive is 100-10000 nanogram/gram, the grain diameter of the sacculus of the product is 10-1000 nanometer. In addition, the invention also relates to the preparation method of preparing antler nanometer product and the application of the product in the aspect of medicine, food, health products and cosmetics and so on.
Description
Technical field
The invention belongs to the medical of Cornu Cervi Pantotrichum extract or edible products field.More specifically, the present invention relates to the nanorize goods made by the Cornu Cervi Pantotrichum extract that is rich in insulin like growth factor (IGF-1).In addition, the invention still further relates to the method for these Cornu Cervi Pantotrichum nanorize goods of preparation, and these goods are in the application of aspects such as medicine, food, health product and cosmetics.
Background technology
Cornu Cervi Pantotrichum (young horn that deer is still unossified) and Cornu Cervi have effects such as strengthening the tendons and bones, kidney invigorating and YANG supporting, mediation governor vessel as traditional Chinese crude drug, and just being widely used in preparation since ancient times becomes various tonics, food, health product and cosmetics.Research and analyse by Modern Pharmaceutical Chemistry, contain many kinds of physiologically active ingredients in the Cornu Cervi Pantotrichum, comprise phospholipid, alkamines chemical compound, prostaglandin, vitamin, aminoacid, inorganic salt, unsaturated fatty acid, hydrocortisone etc.Along with the modern biotechnology high speed development, it is found that in the Cornu Cervi Pantotrichum and except containing above-mentioned various physiologically active ingredient, wherein also to contain insulin like growth factor (IGF-1), insulin, human growth hormone (HGH), growth promotion releasing factor (GHRF-6), nerve growth factor (NGF), epidermal growth factor (EGF), fibroblast growth factor macromole reactive proteins such as (FGF).More than various active component, especially various reactive proteins, mutual synergism, performance effect.Wherein, insulin like growth factor plays a part particularly outstanding.IGF-1 has and promotes fissional effect, can be used in the disease that aspects such as disorder are regulated in treatment and the metabolism of prevention carbohydrate equal energy source, as the disease of aspects such as treatment and prevention carbohydrate metabolism or lipid metabolism, as diabetes etc.Chinese patent application CN1251531A discloses and can utilize IGF-1 to induce or improve tissue growth, propagation or regenerated method, especially utilizes IGF-1 to promote the growth of inner ear tissue; Chinese patent application CN1204263A has disclosed and can utilize IGF-1 treatment brain or spinoneural degenerative disease, as alzheimer's disease (Alzheimer ' s Disease), Parkinson's disease (Parkinson ' s Disease) etc.Aspect the treatment diabetes, also there is lot of documents to disclose and utilizes IGF-1 to treat put into practice (referring to Chinese patent application CN1387440A, the CN1384201A etc.) of aspects such as I type, II type and development of insulin resistance diabetes.
In traditional Cornu Cervi Pantotrichum course of processing, Cornu Cervi Pantotrichum is taken after directly pulverizing, and granule is bigger, causes absorption efficiency low; Sometimes, the processing of Cornu Cervi Pantotrichum need be through steps such as heating decoctions, oven dry, and high temperature can make protein denaturations such as IGF-1 wherein, thus reduction and even lose their effect.Another kind of traditional processing mode is that Cornu Cervi Pantotrichum is immersed in the wine of alcohol in high concentration content, makes medicated wine and takes.But owing to contain the ethanol as organic solvent of high concentration in the wine, can make protein denaturations such as IGF-1, and from the bulky grain Cornu Cervi Pantotrichum, also be unfavorable for dissolving protein such as IGF-1, thereby can cause protein such as IGF-1 destroyed, make that the service efficiency of Cornu Cervi Pantotrichum is low, cause the wasting of resources.In addition, the medicated wine of alcohol in high concentration content has also limited each dose.
In order to improve the service efficiency of Cornu Cervi Pantotrichum material, people have attempted the effective ingredient of the whole bag of tricks extraction Cornu Cervi Pantotrichum.For example, International Patent Application WO 2004/035069A has disclosed a kind of Cornu Cervi goods of diabetes and preparation method thereof that are used to prevent and treat, but only contains 18ng IGF-1 and 0.5ng insulin in per 1 these goods of gram.Chinese patent CN1241943C discloses a kind of extracting method of velvet product, but the material that wherein extracts not prompting can be handled through modifications such as nanorize parcels, to absorb the difficult problem of the Proteolytic enzyme enzymatic degradation of barrier and digestive system when oral in the face of gastrointestinal, cause actual absorption efficient low of effective ingredient such as IGF-1.
People also attempt the effective ingredient that the whole bag of tricks extracts Cornu Cervi Pantotrichum, are prepared into the various goods that help absorbing, and especially are prepared into the goods of nanorize, thereby improve the absorption efficiency of Cornu Cervi Pantotrichum material.For example, Chinese patent application CN1723992A discloses a kind of goods that contain compositions such as nanoscale Pulveratum Cornu Cervi Pantotrichum and Semen Juglandis powder with the ad hoc fashion preparation, as the health product of resisting fatigue and enhancing immunity.But, these goods are in the process of preparation, Cornu Cervi Pantotrichum need extract with alcohol solvent, because ethanol is a kind of organic solvent, low to water soluble protein extraction efficiencies such as IGF-1, and make these protein denaturations easily, destroyed proteinic effects such as IGF-1, cause in the manufactured goods activity of proteins such as IGF-1 low, influenced result of use.Chinese patent CN1166369C discloses a kind of water, vegetable oil and/or animal oil of making Cornu Cervi Pantotrichum or Cornu Cervi has been made gel-like fluid or the suspension that particle diameter is 10～1000nm, but all ground product to Cornu Cervi Pantotrichum in preparation process carry out the nanorize processing, do not have to remove and wherein can not be the cutin composition that human body absorbed in a large number, and use vegetable oil or animal oil can not fully extract water soluble proteins such as IGF-1, make the actual content of IGF-1 in these goods low, and the granule of this nanorize can not effectively be avoided the degraded of the proteolytic enzyme of digestive system.
At the defective that exists in the prior art, through long-term and arduous research, the inventor has obtained a kind of new Cornu Cervi Pantotrichum extract that is rich in insulin like growth factor (IGF-1) and nanorize goods thereof, has overcome above-mentioned defective.The goods of the present invention not only content of IGF-1 are high and kept high activity, made full use of the Cornu Cervi Pantotrichum resource, and the goods of nanorize can bring certain short effect of oozing, and help to overcome the problem that gastrointestinal absorbs barrier and enzyme barrier.In addition, the preparation technology of these goods is reasonable, is convenient to control of quality in large-scale production, and preparation process uses natural material, can biodegradation, avoided the pollution of synthetic product, and more hold easy for consumers to accept.
Summary of the invention
The invention provides a kind of nanorize goods of being made by Cornu Cervi Pantotrichum extract and preparation method thereof, described extract is rich in insulin like growth factor.The present invention also provides the application of these nanorize goods in preparation medicine, food, health product and cosmetics.
In first aspect, the invention provides a kind of nanorize goods of making by Cornu Cervi Pantotrichum extract, it comprises the nanocapsule ball that particle diameter is 10 ~ 1000 nanometers (nm), and the content of insulin like growth factor (IGF-1) is 100 ~ 10000 ng/g in the described extract.The IGF-1 content of the extract in the goods of the present invention is 100 ~ 10000 ng/g extracts, is higher than the IGF-1 content of other known Cornu Cervi Pantotrichum extracts far away, and preferred described IGF-1 content is 1000 ~ 6000ng/ gram, more preferably 1500 ~ 4500ng/ gram.And the particle diameter of the nanocapsule ball in the described goods of goods of the present invention is preferably 10 ~ 1000nm, more preferably 20 ~ 800nm, more preferably 40 ~ 400nm.
Described goods can obtain by following two steps: the extract that at first goes out to be rich in IGF-1 from Cornu Cervi Pantotrichum with solvent extraction; Then the said extracted thing is prepared into the nanorize goods.The present invention preferably selects for use the fresh Cornu Cervi Pantotrichum of fresh Cornu Cervi Pantotrichum or cold preservation as raw material, helps preserving to greatest extent the content and the activity of IGF-1 isoreactivity composition.Term used herein " fresh " refers to gather behind the Cornu Cervi Pantotrichum and just begins to carry out processing and preparing nanorize goods of the present invention or carried out cold preservation in 6 hours, preferred processing or cold preservation were earlier than 3 hours after gathering, choosing is more arranged earlier than 1 hour, most preferably earlier than 20 minutes.Term used herein " cold preservation " refers to Cornu Cervi Pantotrichum is stored in the environment below 0 ℃, preferably is stored in-20 ℃ the environment.
The present invention preferably with water as solvent, extract IGF-1 content and be the extract of 100 ~ 10000ng/ gram, preferred IGF-1 content is 1000 ~ 6000ng/ gram, more preferably 1500 ~ 4500ng/ gram.And the generation of nanorize goods can adopt supersonic jet method or polymer pack to prepare nano level granule or capsule ball.Preferred goods of the present invention are nano level capsule ball, and it adopts polymer parcel Cornu Cervi Pantotrichum extract to form nano level capsule ball.Synthetic polymer of suitable polymers useful monomers and aliphatic category polyester polymer.Monomer example with the synthetic polymer of monomer has acrylamide, acrylate and alkyl cyanoacrylate and their derivant.Owing to mostly be synthetic, such many polymer can not be biodegradation, and therefore goods of the present invention preferably comprise and have good biodegradable aliphatic category polyester polymer, form nano level capsule ball thus.The example of this base polymer has polylactic acid (PLA), poly-Acetic acid, hydroxy-, bimol. cyclic ester (PLG), poly (glycolide-co-lactide) copolymer (PLGA), polycaprolactone (PCL), polyamino acid and their derivant etc., preferred polyamino acid.Other preferred examples are some natural polymerses and their derivant, optionally natural polymers has albumin, chitosan, glucosan, alginate etc., they have good biodegradable character, can form the nanocapsule bag after the dispersion and wrap up in active component.
Nanorize goods of the present invention especially preferably contain the nanocapsule ball that particle diameter is 100 ~ 400nm.In a specific embodiment, contain chitosan in the nanorize goods of the present invention, use chitosan parcel Cornu Cervi Pantotrichum extract, forming particle diameter is the nanocapsule ball of 100 ~ 400nm.The Cornu Cervi Pantotrichum extract of chitosan parcel is except having certain short osmosis to peptide matters wherein, and because chitosan has more preceding mucoadhesive properties, also can suppress certain proteasome degradation, prevent that active ingredients such as IGF-1 just are degraded before absorption.In addition, at chitosan infix and protease inhibitor,, also can reduce the Degradation of protease as inhibitors of metalloproteinase such as EDTA.Therefore, the nanorize goods that contain chitosan of the present invention especially are fit to further be processed into oral products, as mouth spraying agent, tablet, capsule etc.
Nanorize goods of the present invention also preferably contain the nanocapsule ball that particle diameter is 50 ~ 150nm.In a specific embodiment, contain polyamino acid in the nanorize goods of the present invention, use polyamino acid parcel Cornu Cervi Pantotrichum extract, forming particle diameter is the nanocapsule ball of 50 ~ 150nm.The polyamino acid (referring to International Patent Application WO 96/029991A) that polyamino acid can be selected from poly-D-lysine and be made up of leucine and glutamic acid.
Nanorize goods of the present invention can also further comprise pharmaceutically acceptable adjuvant except containing above-mentioned Cornu Cervi Pantotrichum extract and polymer lapping, thereby process various dosage forms.Pharmaceutically acceptable adjuvant comprises pharmaceutically acceptable carrier, excipient, diluent etc., and they are compatible with active component.Using pharmaceutically acceptable adjuvant to prepare preparation is known for those of ordinary skills.Preparation of the present invention comprises the described nanorize goods in first aspect of one or more the present invention as active component, these nanorize goods and pharmaceutically acceptable adjuvant (as carrier well known to those of ordinary skill in the art, excipient, diluent etc.) are combined, be mixed with various preparations, be preferably solid preparation and liquid preparation.Preferred preparation of the present invention is a unit dosage form, as dosage forms such as tablet, pill, capsule (comprise and continue to discharge or postpone releasing pattern), powder, suspensoid, granule, tincture, syrup, emulsion agent, suspension, injections, thereby be fit to various form of medication, for example oral, non-intestinal injection, mucosa, muscle, intravenous, subcutaneous, ophthalmic, Intradermal or through the form of medication of skin etc.Nanorize goods of the present invention are especially preferably made mouth spraying agent, capsule or injection.Wherein carrier, excipient, diluent are pharmaceutically acceptable and compatible with active component.The suitable excipient that can select for use is preferred but be not limited only to water, normal saline, glucose, glycerol, ethanol or its analog and combination thereof.
In second aspect, the invention provides the application of nanorize goods in medicine, health food and/or the cosmetics of preparation promotion cell proliferation of first aspect present invention.Nanorize goods of the present invention are made by the Cornu Cervi Pantotrichum extract that is rich in IGF-1, has the effect that promotes cell division, propagation, can be used for inducing or improving patient's tissue growth, propagation or regenerated level, treat corresponding disease, for example brain or spinoneural degenerative disease are as alzheimer's disease, Parkinson's disease etc.Owing to be natural product, and Cornu Cervi Pantotrichum itself has long use history, and healthy people takes a certain amount of nanorize goods of the present invention and helps to keep its normal cell division, proliferation function, helps to keep its abundant vigor.A certain amount of nanorize goods of the present invention of healthy people's external help to keep division, the propagation of its Skin Cell, improve outside image, have the effect of beauty treatment.
In the third aspect, the nanorize goods that the invention provides first aspect present invention treat and/or prevent carbohydrate metabolism in preparation and regulate disorderly medicine and/or the application in the health food.Nanorize goods of the present invention are made by the Cornu Cervi Pantotrichum extract that is rich in IGF-1, can be used in and treat and/or prevent disease or the sub-health state that aspects such as disorder are regulated in the metabolism of carbohydrate equal energy source, disease as aspects such as treatment and prevention carbohydrate metabolism or lipid metabolism, particularly diabetes comprise I type, II type and development of insulin resistance diabetes etc.
For the medicine of the present invention second and the third aspect, nanorize goods of the present invention can be processed into various pharmaceutical dosage forms, and needs are promoted cell proliferation or need treat and/or prevent carbohydrate metabolism to regulate disorderly patient's administration.The dosage of administration and form are generally determined according to patient's concrete condition (as age, body weight, sex, the state of an illness, sick time, health etc.) by the doctor.Generally speaking, in the IGF-1 in the nanorize goods, the dosage of administration is 0.001～100mg/kg weight in patients, is preferably 0.01～1mg/kg, is preferably 0.02～0.1mg/kg.Form of medication can be determined according to the dosage form of various pharmaceutical preparatioies, the form of medication that is fit to has oral, non-intestinal injection, mucosa, muscle, intravenous, subcutaneous, ophthalmic, Intradermal or through form of medication such as skins, preferably uses mouth spraying agent or capsule oral administration.
In the application of the present invention second and the third aspect, nanorize goods of the present invention can use as medicine, health food and/or cosmetics separately, also can add in other medicines, health food and/or the cosmetics and use.For example, nanorize goods of the present invention can add fit applications in conventional beverage, food or the cosmetics to.
In fourth aspect, the invention provides the preparation method of the nanorize goods of first aspect present invention.This preparation method can comprise following two steps: at first extract the extract that is rich in IGF-1 from Cornu Cervi Pantotrichum; Then the said extracted thing is prepared into the nanorize goods.This preparation method preferably includes the following step:
A) Cornu Cervi Pantotrichum of pulverizing with flooding is isolated the water solubility extract that molecular weight is 500 ~ 500000Da, lyophilization;
And b) with biodegradable polymer the extract of step a) gained is rolled into the nanocapsule ball.
Wherein, the step of pulverizing Cornu Cervi Pantotrichum in the step a) can comprise one or more in the modes such as section, homogenate, ultrasonic disruption." section " refers to Cornu Cervi Pantotrichum laminated, and preferably uses microtome that the fresh Cornu Cervi Pantotrichum of fresh Cornu Cervi Pantotrichum or cold preservation is cut into the thin slice that thickness is 1 ~ 5mm." homogenate " refer to Pulveratum Cornu Cervi Pantotrichum be broken to do not have a big piece of tissue till, can add proper amount of deionized water in the homogenate process.Through ultrasonic disruption, can fully make cell rupture, can add proper amount of deionized water in this shattering process.The step of pulverizing Cornu Cervi Pantotrichum preferably comprises section, homogenate and ultrasonic disruption step in order, also can omit slicing step wherein.The overall process of pulverizing Cornu Cervi Pantotrichum is preferably in the low temperature environment operates, and use therein reagent is preferably low temperature pre-cooling also, and low temperature environment refers to the environment at 0 ~ 20 ℃, and preferred 0 ~ 10 ℃ environment is preferably in 4 ℃.The step of the Cornu Cervi Pantotrichum of pulverizing with flooding in the step a) can be finished simultaneously with the step of pulverizing Cornu Cervi Pantotrichum, promptly come the effective ingredient of lixiviate Cornu Cervi Pantotrichum by the water that in steps such as section, homogenate and/or ultrasonic disruption, adds, as IGF-1, lixiviate is finished naturally along with finishing of pulverising step; Also can further place a period of time again after the step of pulverizing Cornu Cervi Pantotrichum and carry out lixiviate, the described time preferably placed 24 hours as being no more than 36 hours, preferably can be placed in the low temperature environment.The step of in the step a) water solubility extract being separated can be undertaken by the modes such as centrifugal and/or filtration of routine, as super centrifugal and/or ultrafiltration etc.Preferred extraction molecular weight is the composition of 500 ~ 500000Da in this step, and more having choosing to extract molecular weight is the composition of 1000 ~ 100000Da, most preferably extracts the composition that molecular weight is 1000 ~ 10000Da.A specific embodiment, the present invention by the precipitation in the centrifugal removal flooding product, selects for use suitable ultrafilter membrane to hold back the composition of corresponding molecular weight earlier then, adds the water dissolution of appropriate amount again.Carry out lyophilization then, carry out drying as the aqueous solution that uses freezer dryer will go up the composition that is dissolved with corresponding molecular weight of step gained with-30 ℃ ~-50 ℃ drying machine operating temperature, the water content of dry back product is 3%-10%.
In step b), the end product of step a) gained is carried out nanorize, it can adopt supersonic jet method or polymer pack to prepare nano level granule or capsule ball." supersonic jet method " is meant and uses supersonic jet equipment (as can be available from Beijing nano bio tech ltd) that Cornu Cervi Pantotrichum extract is formed high velocity jet, and the multiply injection stream is crossed at a high speed mutually in the pulverizing district, produce high velocity impact and grinding, thereby form nano level granule.The present invention preferably adopts the mode of polymer parcel Cornu Cervi Pantotrichum extract to form nano level capsule ball.Synthetic polymer of its suitable polymers useful monomers and aliphatic category polyester polymer.Monomer example with the synthetic polymer of monomer has acrylamide, acrylate and alkyl cyanoacrylate and their derivant.The step of preparation nanoscale capsule ball comprises Cornu Cervi Pantotrichum extract added in the acidic aqueous media that contains emulsifying agent (as glucosan, polysorbate etc.) with monomer, and (anion normally is as OH to add polymerization initiator
-) polyreaction of trigger monomer, make Cornu Cervi Pantotrichum extract embedding in polymerization process advance in the nanoscale capsule ball.Because monomer mostly is synthetic, such many polymer can not be biodegradation, and therefore goods of the present invention preferably comprise and have good biodegradable aliphatic category polyester polymer, form nano level capsule ball thus.The example of this base polymer has polylactic acid (PLA), poly-Acetic acid, hydroxy-, bimol. cyclic ester (PLG), poly (glycolide-co-lactide) copolymer (PLGA), polycaprolactone (PCL), polyamino acid and their derivant etc., other preferred examples are some natural polymerses and their derivant, optionally natural polymers has albumin, chitosan, glucosan, alginate etc., they have good biodegradable polylactic acid, can form the nanocapsule bag after the dispersion and wrap up in active component.This base polymer can adopt back dispersion method parcel Cornu Cervi Pantotrichum extract, and concrete example has modes such as the solvent evaporation of employing or spontaneous emulsification/solvent diffuse to wrap up.Solvent evaporated method refers to, polymer and Cornu Cervi Pantotrichum extract are dissolved in the organic solvent, organic solvent is added to carries out emulsifying in the aqueous systems that contains emulsifying agent, then by heat, modes such as decompression or continuous stirring remove organic solvent evaporation, form the aqueous dispersion of polymer nanocomposite capsule ball.Spontaneous emulsification/solvent diffusion method refers to, mixed solvent dissolve polymer and Cornu Cervi Pantotrichum extract with hydrophilic organic solvent and hydrophobic organic solvent formation, it is distributed in the water,, thereby forms the nanocapsule ball because hydrophilic organic solvent can be diffused into water from oil phase automatically.In a specific embodiment, the polymer that uses in the preparation method of the present invention is chitosan, promptly uses chitosan parcel Cornu Cervi Pantotrichum extract, and forming particle diameter is the nanocapsule ball of 100 ~ 400nm.In another embodiment, the polymer that uses in the preparation method of the present invention is polyamino acid, promptly uses polyamino acid parcel Cornu Cervi Pantotrichum extract, and forming particle diameter is the nanocapsule ball of 50 ~ 150nm.The polyamino acid that polyamino acid can be selected from poly-D-lysine and be made up of leucine and glutamic acid.
The present invention has quoted open source literature, and these documents are in order more clearly to describe the present invention, and their full text content is all included this paper in and carried out reference, just looks like that repeated description is the same excessively in this article for their full text.
For the ease of understanding, below will describe in detail the present invention by specific embodiment.It needs to be noted that these descriptions only are exemplary descriptions, do not constitute limitation of the scope of the invention.According to the argumentation of this description, many variations of the present invention, change have been obviously all concerning one of ordinary skill in the art.
Embodiments of the invention
Embodiment 1, the extraction of effective constituent of pilose antler
Get fresh Cornu Cervi Pantotrichum 0.5kg, with freezing microtome Cornu Cervi Pantotrichum is cut into the section that thickness is 1 ~ 2mm, the deionized water that adds an amount of (200mL) pre-cooling is then pulverized with refiner at 4 ℃, and the homogenate operation does not proceed to when having big piece of tissue in the homogenate and finishes.In the product of preliminary pulverizing, add the deionized water of 1L pre-cooling then, under condition of ice bath, carry out ultrasonic disruption behind the mixing.Suspension after then should fragmentation centrifugal 20 minutes with 5000 rev/mins (rpm) stays supernatant stand-by.Precipitate after centrifugal adds the deionized water of 1L pre-cooling, and ultrasonic disruption is carried out in concussion evenly back under condition of ice bath, and then with 5000 rev/mins centrifugal 20 minutes, stay supernatant stand-by.Precipitate after centrifugal repeats above-mentioned steps again, add entry, ultrasonic Treatment, centrifugal after, stay supernatant stand-by.3 parts of supernatant that obtain in the above step are mixed, then carry out 2 ultrafiltration.The ultrafiltration molecular cut off is that the ultrafilter membrane of 100000Da (available from Millopore, Ultrapore), keeps filter liquor first.Be that (available from Millopore, ultrafilter membrane Ultrapore) carries out ultrafiltration to 1000Da, discards filter liquor then with the filter liquor molecular cut off.With the material that the deionized water stripping ultrafilter membrane of 200mL pre-cooling is held back, it is stand-by to keep dissolution fluid.To discard ultrafilter membrane through the deionized water stripping of the ultrafilter membrane reuse 200mL pre-cooling of stripping step for the first time, merge twice dissolution fluid of gained.Use freezer dryer at-30 ~-50 ℃ of lyophilization dissolution fluids, get dried thick product 22 grams, wherein the water content of this thick product is no more than 8%.
With the IGF-1ELISA detection kit (available from U.S. R﹠amp; D Systems company, catalog number: DG100) detect IGF-1 content in the thick product that above leaching process obtains.Accurately take by weighing the thick product of 10mg, be dissolved in the 1ml deionized water, according to the test kit operating instruction detection of manufacturer, read content from standard I GF-1 detection curve, the content of IGF-1 is 2384 nanograms (ng) in the thick product of above-mentioned every gram.
Embodiment 2, the extraction of effective constituent of pilose antler
Use the step similar to extract to embodiment 1.Used step and embodiment 1 different place mainly is: use cold preservation in-20 ℃ Cornu Cervi Pantotrichum; And carry out ultrasonic disruption under condition of ice bath after, static placement suspension 24 hours is with abundant stripping active component.Detailed process is as follows: cold preservation is got this Cornu Cervi Pantotrichum 0.5kg in-20 ℃ of refrigerators 10 days after the fresh Cornu Cervi Pantotrichum collection, with freezing microtome Cornu Cervi Pantotrichum is cut into the section that thickness is 1 ~ 2mm, adds suitable quantity of water then and pulverizes with refiner at 4 ℃.Add the deionized water of 1L pre-cooling then to the product of preliminary pulverizing, under condition of ice bath, carry out ultrasonic disruption behind the mixing.The static placement of suspension after then should fragmentation 24 hours is with abundant stripping active substance.Then, with suspension centrifugal 20 minutes, stay supernatant stand-by with 5000 rev/mins (rpm).Precipitate after centrifugal adds the deionized water of 1L pre-cooling, after the concussion evenly again with 5000 rev/mins centrifugal 20 minutes, stay supernatant stand-by.Precipitate after centrifugal repeats above-mentioned steps again, add entry, mixing, centrifugal after, stay supernatant stand-by.3 parts of supernatant that obtain in the above step are mixed, then carry out 2 ultrafiltration.The ultrafiltration molecular cut off is the ultrafilter membrane of 100000Da first, keeps filter liquor.The ultrafilter membrane that with the filter liquor molecular cut off is 1000Da then carries out ultrafiltration, discards filter liquor.With the material that the deionized water stripping ultrafilter membrane of 200mL pre-cooling is held back, it is stand-by to keep dissolution fluid.To discard ultrafilter membrane through the deionized water stripping of the ultrafilter membrane reuse 200mL pre-cooling of stripping step for the first time, merge twice dissolution fluid of gained.Use freezer dryer at-30 ~-50 ℃ of lyophilization dissolution fluids, get dried thick product 24 grams, wherein the water content of this thick product is no more than 8%.
Detect IGF-1 content in the thick product that above leaching process obtains with the IGF-1ELISA detection kit, the content that records IGF-1 in the thick product of above-mentioned every gram is 1832ng.
Embodiment 3, the extraction of effective constituent of pilose antler
Use the step identical with embodiment 1 with fresh Cornu Cervi Pantotrichum 0.5kg cut into slices, ultrasonic disruption, carry out 2 ultrafiltration then.The ultrafiltration molecular cut off is that (available from Millopore, ultrafilter membrane Ultrapore) keeps filter liquor to 10000Da first.The ultrafilter membrane that with the filter liquor molecular cut off is 1000Da then carries out ultrafiltration, discards filter liquor.With the material that the deionized water stripping ultrafilter membrane of 200mL pre-cooling is held back, it is stand-by to keep dissolution fluid.To discard ultrafilter membrane through the deionized water stripping of the ultrafilter membrane reuse 200mL pre-cooling of stripping step for the first time, merge twice dissolution fluid of gained.Use freezer dryer at-30 ~-50 ℃ of lyophilization dissolution fluids, get dried thick product 10 grams, wherein the water content of this thick product is no more than 8%.
Detect IGF-1 content in the thick product that above leaching process obtains with the IGF-1ELISA detection kit, the content that records IGF-1 in the thick product of above-mentioned every gram is 4315ng.
Embodiment 4, with Preparation of Chitosan nanorize velvet product
Be averaged relative molecular weight and be the thick product 5mg that 45000 chitosan (available from Zhejiang University) 120mg and the foregoing description make, they are dissolved in 12mL 1% acetum.Then this chitosan-acetic acid solution slowly is added drop-wise to 150mL and contains in the 20% alcoholic acid sorbester p37 solution (available from Shanghai chemical reagents corporation), take out the branch that anhydrates in 40 ℃ of decompressions.To obtain product then centrifugal 20 minutes with 5000rpm, abandoning supernatant, precipitation is with petroleum ether 2 times.Add 20 ml waters to precipitation then,, promptly get the nanocapsule ball suspension of chitosan parcel with ultrasonic Treatment.With 20 times of the nanocapsule ball suspension thin ups of above-mentioned chitosan parcel, get in right amount on copper mesh, carry out negative staining with 2% Sodium phosphotungstate, utilize transmission electron microscope to observe then, the size of the nanocapsule ball of gained is 100 ~ 400nm.Repeat above preparation process preparation, but wherein do not add the thick product of Cornu Cervi Pantotrichum, make blank nanocapsule ball suspension thus as blank.
Detect the envelop rate of above nanorize velvet product with the IGF-1ELISA detection kit.Proper amount of nano capsule ball suspension is divided into 2 parts (dosage of the IGF-1 in every duplicate samples is counted W0), and a copy of it detects free with the IGF-1ELISA detection kit and is adsorbed on the amount (W1) of the IGF-1 of nano grain surface; Another part used 0.5U/mL chitosanase (available from Japanese chemical industrial company) enzymolysis 6 hours, and then detects the amount (W2) of IGF-1 with the IGF-1ELISA detection kit.According to the formula of envelop rate=(W2-W1)/W0*100%, the envelop rate of the said goods that records is 68%.
Embodiment 5, prepare the nanorize velvet product with polyamino acid
The thick product 10mg that the foregoing description is made is dissolved among the PBS (wherein containing 0.01mol/L phosphate, 0.138mol/L NaCl and 0.0027mol/L KCl) of 12mL pH7.4.Be averaged relative molecular weight and be 23000 poly-Leu/Glu-50/50 (available from Chinese Academy Of Sciences Process Engineering Research Institute, wherein contain 50% leucine and 50% glutamic acid) 50mg, it is dispersed in the above-mentioned PBS solution, forms the colloidal dispersion (the nanorize velvet product of polyamino acid parcel) that contains the nanocapsule ball automatically.This liquid is can scattered light existing, and places 15 ℃ precipitation to occur after 3 hours.Get the nanorize velvet product of above-mentioned polyamino acid parcel, utilize transmission electron microscope to observe, the size of the nanocapsule ball of gained is 50 ~ 150nm.
Embodiment 6, the IGF-1 determination of activity in the nanorize velvet product
Stimulate the propagation of the Ba1b-3T3 cell that 96 orifice plates cultivate respectively with the nanocapsule ball suspension of embodiment 4 preparation and blank.With Mus tail glue primordial covering 96 well culture plates, stand-by on ice with DMEM dilution postposition.After 30 minutes, in plate hole, add 50 μ L nanocapsule ball suspension and blanks respectively, put the incubator inner equilibrium 60 minutes.Then add 50 μ L MTT, hatched 4 hours at 37 ℃.Add 100 μ L DMSO then, temperature was bathed 1 hour.Because living cells can change into tetrazolium salts can be by the dissolved coloured product of DMSO, its output is directly proportional with living cells quantity, therefore surveys absorbance with microplate reader under 570nm, can estimate viable count.With respect to blank, use nanorize velvet product of the present invention can significantly improve the rate of increase of Ba1b-3T3 cell.
Embodiment 7, and the IGF-1 antienzyme degrading activity in the nanorize velvet product is measured
The propagation that stimulates the Ba1b-3T3 cell of 96 orifice plates cultivation respectively with the nanocapsule ball suspension of embodiment 4 preparation, nanocapsule ball suspension that pancreatin was handled and blank.Wherein, handled 2 hours for 37 ℃, be prepared into the nanocapsule ball suspension that pancreatin was handled with pancreatin.Detect the multiplication effect of cell with the experimental procedure identical, measure absorbance with embodiment 6.The activity of the said goods that records thus IGF-1 behind enzymatic degradation still keeps 81% activity with respect to without enzymatic degradation.
Claims (9)
1. nanorize goods of making by Cornu Cervi Pantotrichum extract, wherein the particle diameter of nanocapsule ball is 100～400nm, wherein contains chitosan, and the content of insulin-like growth factor-i is 1000～6000ng/ gram in the described extract; And described nanorize goods are made by the preparation method that comprises the following steps:
A) Cornu Cervi Pantotrichum of pulverizing with flooding is isolated the water solubility extract that molecular weight is 500～500000Da, lyophilization;
And b) with chitosan the extract of step a) gained is rolled into the nanocapsule ball.
2. according to the nanorize goods of claim 1, the content of insulin-like growth factor-i is 1500～4500ng/ gram wherein and in the described extract.
3. nanorize goods of making by Cornu Cervi Pantotrichum extract, wherein the particle diameter of nanocapsule ball is 50～150nm, wherein contains polyamino acid, and the content of insulin-like growth factor-i is 1000～6000ng/ gram in the described extract; And described nanorize goods are made by the preparation method that comprises the following steps:
A) Cornu Cervi Pantotrichum of pulverizing with flooding is isolated the water solubility extract that molecular weight is 500～500000Da, lyophilization;
And b) with polyamino acid the extract of step a) gained is rolled into the nanocapsule ball.
4. according to the nanorize goods of claim 3, the content of insulin-like growth factor-i is 1500～4500ng/ gram wherein and in the described extract.
5. according to arbitrary nanorize goods of claim 1-2, it is mouth spraying agent, capsule or injection.
6. according to arbitrary nanorize goods of claim 3-4, it is mouth spraying agent, capsule or injection.
7. the application of arbitrary nanorize goods of claim 1-6 in medicine, health food and/or the cosmetics of preparation promotion cell proliferation.
8. arbitrary nanorize goods of claim 1-6 treat and/or prevent carbohydrate metabolism in preparation and regulate disorderly medicine and/or the application in the health food.
9. arbitrary nanorize goods of claim 1-6 treat and/or prevent the medicine of diabetes and/or the application in the health food in preparation.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2006/000841 WO2007124618A1 (en) | 2006-04-28 | 2006-04-28 | Insulin-like growth factor-enriched nano-products of hairy antler and process for preparation thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101068556A CN101068556A (en) | 2007-11-07 |
| CN101068556B true CN101068556B (en) | 2010-11-10 |
Family
ID=38655033
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2006800012623A Expired - Fee Related CN101068556B (en) | 2006-04-28 | 2006-04-28 | Pilose antler nano-products containing enriched insulin-like growth factor and producing method thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN101068556B (en) |
| WO (1) | WO2007124618A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109486749A (en) * | 2017-09-11 | 2019-03-19 | 广西索芙特集团有限公司 | Velvet deerhorn cell Serium-free Culture |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1241943C (en) * | 2004-08-04 | 2006-02-15 | 王利忠 | Method for extracting insulin-like growth factor (IGF-1) from fresh antler |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1408368A (en) * | 2001-09-27 | 2003-04-09 | 成都思摩纳米技术有限公司 | Method for preparing nano pilose antler suspension |
| CN1166369C (en) * | 2001-11-07 | 2004-09-15 | 焦柏忠 | Nanometer level pilose antler and pilose antler product and their prepn process |
| CN100390199C (en) * | 2005-10-25 | 2008-05-28 | 天津大学 | Method for extracting insulin type growth factor-1 from fresh pilose antler |
-
2006
- 2006-04-28 WO PCT/CN2006/000841 patent/WO2007124618A1/en active Application Filing
- 2006-04-28 CN CN2006800012623A patent/CN101068556B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1241943C (en) * | 2004-08-04 | 2006-02-15 | 王利忠 | Method for extracting insulin-like growth factor (IGF-1) from fresh antler |
Non-Patent Citations (4)
| Title |
|---|
| 元英进等主编.中药现代化生产关键技术 第1版.化学工业出版社出版,2002,203-205. |
| 元英进等主编.中药现代化生产关键技术 第1版.化学工业出版社出版,2002,203-205. * |
| 李玉宝主编.纳米生物医药材料 第1版.化学工业出版社出版,2004,135. |
| 李玉宝主编.纳米生物医药材料 第1版.化学工业出版社出版,2004,135. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101068556A (en) | 2007-11-07 |
| WO2007124618A1 (en) | 2007-11-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101007865B1 (en) | Sustained-release chitosan capsules comprising chitosan and phytic acid | |
| TW495361B (en) | Single-shot vaccine formulation | |
| KR20230093248A (en) | Targeted transport system loaded with whole cell components and uses thereof | |
| SK11192001A3 (en) | Freeze-dried agent containing paramylon, production and utilization thereof | |
| CN112438944B (en) | Temperature-sensitive gel pharmaceutical composition for treating tumors | |
| CN110101684A (en) | A kind of cellular membrane biomimetic nano particle and its preparation method and application of bio-orthogonal targeting | |
| CN101020715B (en) | Process of extracting and preparing deer nerve growth factor (DEER NGF) | |
| JP2006527265A (en) | Composition for enteric coating of natural product containing lectin | |
| CN101690716A (en) | Calcium alginate-chitosan sustained-release microsphere carrying growth hormone and application thereof | |
| CN108685927A (en) | Include the medical composition and its use of methylenum careuleum class compound and bioactive ingredients | |
| CN103976976B (en) | A kind of bag carries the method for making of human growth hormone recombinant's small capsule of slow-soluble medicine | |
| WO2017220615A1 (en) | Method and apparatus for preparing a micro-particles composition | |
| CN108686216A (en) | Include the medical composition and its use of chemical ablation agent and bioactive polysaccharide | |
| CN104490933B (en) | Crocodile blood nano microcapsule and preparation method thereof | |
| CN101068556B (en) | Pilose antler nano-products containing enriched insulin-like growth factor and producing method thereof | |
| CN100556400C (en) | The preparation method of the polysaccharide vitreous particle of carrying active vaccine or antibody | |
| KR20210012979A (en) | Levan-protein nanocomposite and uses thereof | |
| CN101054414B (en) | Method of extracting and preparing deer DGF | |
| CN1301747C (en) | Protein medicine microcapsule and inhalational aerosol thereof | |
| CN101081865B (en) | Abstraction of pilose antler releasing somatomedin (DEER GHRF) and preparation method thereof | |
| US20030206957A1 (en) | Orally administered medicament delivery systems | |
| CN101518645A (en) | Application of marine collagen peptide in preparing drugs, health care food or food for protecting renal function and delaying the process of chronic renal failure | |
| CN100438915C (en) | Targeted nanometer medicine carrier and its prepn. method | |
| FRIESS et al. | In‐vivo activity of collagen matrices containing PS1, an antineoplastic glycan, against murine sarcoma cells | |
| KR101281084B1 (en) | Polyoxalate particle as new biodegradable and biocompatible drug delivery vehicle |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20160907 Address after: Wenjiang District of Chengdu City, 611130 West Road in Sichuan province No. 418 Patentee after: CHENGDU RUNXINTANG PHARMACEUTICAL Co.,Ltd. Address before: Haining City, Jiaxing Haichang Road No. 49 of 314400 cities in Zhejiang Province Patentee before: Wang Lizhong |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20101110 |