CN110538145B - Phloretin solubilization solid dispersion with stevioside as carrier and preparation method thereof - Google Patents
Phloretin solubilization solid dispersion with stevioside as carrier and preparation method thereof Download PDFInfo
- Publication number
- CN110538145B CN110538145B CN201910948738.3A CN201910948738A CN110538145B CN 110538145 B CN110538145 B CN 110538145B CN 201910948738 A CN201910948738 A CN 201910948738A CN 110538145 B CN110538145 B CN 110538145B
- Authority
- CN
- China
- Prior art keywords
- phloretin
- stevioside
- solid dispersion
- carrier
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- VGEREEWJJVICBM-UHFFFAOYSA-N phloretin Chemical compound C1=CC(O)=CC=C1CCC(=O)C1=C(O)C=C(O)C=C1O VGEREEWJJVICBM-UHFFFAOYSA-N 0.000 title claims abstract description 352
- ZWTDXYUDJYDHJR-UHFFFAOYSA-N (E)-1-(2,4-dihydroxyphenyl)-3-(2,4-dihydroxyphenyl)-2-propen-1-one Natural products OC1=CC(O)=CC=C1C=CC(=O)C1=CC=C(O)C=C1O ZWTDXYUDJYDHJR-UHFFFAOYSA-N 0.000 title claims abstract description 176
- YQHMWTPYORBCMF-UHFFFAOYSA-N Naringenin chalcone Natural products C1=CC(O)=CC=C1C=CC(=O)C1=C(O)C=C(O)C=C1O YQHMWTPYORBCMF-UHFFFAOYSA-N 0.000 title claims abstract description 176
- 235000019202 steviosides Nutrition 0.000 title claims abstract description 172
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 title claims abstract description 132
- 229940013618 stevioside Drugs 0.000 title claims abstract description 132
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 title claims abstract description 132
- 239000007962 solid dispersion Substances 0.000 title claims abstract description 81
- 238000005063 solubilization Methods 0.000 title claims abstract description 21
- 230000007928 solubilization Effects 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000000654 additive Substances 0.000 claims abstract description 7
- 239000001512 FEMA 4601 Substances 0.000 claims description 52
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 claims description 52
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 claims description 52
- 235000019203 rebaudioside A Nutrition 0.000 claims description 52
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 claims description 52
- 239000004383 Steviol glycoside Substances 0.000 claims description 39
- 235000019411 steviol glycoside Nutrition 0.000 claims description 39
- 229930182488 steviol glycoside Natural products 0.000 claims description 39
- 150000008144 steviol glycosides Chemical class 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- 239000000843 powder Substances 0.000 claims description 15
- 230000003381 solubilizing effect Effects 0.000 claims description 7
- 230000000996 additive effect Effects 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 238000009210 therapy by ultrasound Methods 0.000 claims description 5
- 235000013361 beverage Nutrition 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 238000000227 grinding Methods 0.000 claims description 3
- 238000003760 magnetic stirring Methods 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 238000007873 sieving Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 24
- 235000013305 food Nutrition 0.000 abstract description 18
- 210000004369 blood Anatomy 0.000 abstract description 6
- 239000008280 blood Substances 0.000 abstract description 6
- 238000005516 engineering process Methods 0.000 abstract description 6
- 230000008569 process Effects 0.000 abstract description 6
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- 239000006069 physical mixture Substances 0.000 description 41
- 239000012876 carrier material Substances 0.000 description 35
- 239000000243 solution Substances 0.000 description 22
- 239000000523 sample Substances 0.000 description 18
- 239000012153 distilled water Substances 0.000 description 12
- 239000006228 supernatant Substances 0.000 description 10
- 238000000527 sonication Methods 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 229940098773 bovine serum albumin Drugs 0.000 description 7
- 239000004530 micro-emulsion Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000000502 dialysis Methods 0.000 description 5
- 230000001186 cumulative effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 235000013373 food additive Nutrition 0.000 description 4
- 239000002778 food additive Substances 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 230000000171 quenching effect Effects 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 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 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- OEANUJAFZLQYOD-CXAZCLJRSA-N (2r,3s,4r,5r,6r)-6-[(2r,3r,4r,5r,6r)-5-acetamido-3-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxy-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](OC)O[C@H](CO)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](OC)[C@H](C(O)=O)O1 OEANUJAFZLQYOD-CXAZCLJRSA-N 0.000 description 1
- 229910002483 Cu Ka Inorganic materials 0.000 description 1
- 229920000045 Dermatan sulfate Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes 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
- 102000058058 Glucose Transporter Type 2 Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 244000141359 Malus pumila Species 0.000 description 1
- 235000011430 Malus pumila Nutrition 0.000 description 1
- 235000015103 Malus silvestris Nutrition 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091006299 SLC2A2 Proteins 0.000 description 1
- 108091006277 SLC5A1 Proteins 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 102000058090 Sodium-Glucose Transporter 1 Human genes 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- QFVOYBUQQBFCRH-UHFFFAOYSA-N Steviol Natural products C1CC2(C3)CC(=C)C3(O)CCC2C2(C)C1C(C)(C(O)=O)CCC2 QFVOYBUQQBFCRH-UHFFFAOYSA-N 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002288 cocrystallisation Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 description 1
- PXLWOFBAEVGBOA-UHFFFAOYSA-N dihydrochalcone Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=CC(C(=O)CC(O)C=2C=CC(O)=CC=2)=C1O PXLWOFBAEVGBOA-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- -1 exists in root bark Chemical class 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002121 nanofiber Substances 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- QFVOYBUQQBFCRH-VQSWZGCSSA-N steviol Chemical compound C([C@@]1(O)C(=C)C[C@@]2(C1)CC1)C[C@H]2[C@@]2(C)[C@H]1[C@](C)(C(O)=O)CCC2 QFVOYBUQQBFCRH-VQSWZGCSSA-N 0.000 description 1
- 229940032084 steviol Drugs 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
- A23L2/60—Sweeteners
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Polymers & Plastics (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Mycology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Botany (AREA)
- Saccharide Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a phloretin solubilized solid dispersion with stevioside as a carrier and a preparation method thereof. The technical scheme is characterized in that stevioside is used as a carrier, phloretin is used as a dispersoid, the preparation method is carried out through a solvent method, and 26-30 mg of phloretin can be completely solubilized in water per 500mg of stevioside. The solid dispersion can effectively improve the solubility and the release degree of phloretin, and simultaneously solves the problems of complex formula, complex process, inapplicability to food and the like in the conventional solubilization technology; the method has simple and safe process and low requirement on equipment, and is suitable for industrial-level large-scale production; besides, stevioside and phloretin are both additives suitable for blood sugar-reducing foods and can be used in various food water systems.
Description
Technical Field
The invention relates to the technical field of compound solubilization, and particularly relates to a phloretin solubilization solid dispersion with stevioside as a carrier and a preparation method thereof.
Background
Phloretin (PT) is a dihydrochalcone plant flavone, mainly exists in root bark, stem, leaf and pericarp of apple tree, and can be used as natural spice for food. A large number of researches show that phloretin has multiple biological activities of oxidation resistance, bacteriostasis, tumor resistance, inflammation resistance, immunosuppression, cell protection, tyrosinase inhibition, blood sugar reduction and the like, and has strong market prospects in the fields of foods, medicines, cosmetics and the like. At present, phloretin has been widely used as a novel natural whitening agent in the field of cosmetics. However, phloretin has very poor solubility in water (20. mu.g/mL), low oral bioavailability and serious problems in application in the fields of food and medicine.
Steviol glycosides (steviosides, STE), a novel natural sweetener extracted from the plant stevia rebaudiana, has been evaluated for safety by JECFA (the committee on experts in food additives for grain and agriculture organization of the world health organization and the united nations), and is listed as a sweetener in the national standard for food additives for food safety (GB 2760). Stevioside and rebaudioside A are the two main components in stevioside, and are terpenoids consisting of a hydrophobic steviol central skeleton and hydrophilic bilateral glycosyl groups, and have typical amphiphilic structures, so that the stevioside and rebaudioside A become natural solid surfactants and can improve the solubility of insoluble substances. Simultaneously, stevioside cannot be decomposed and digested by enzymes of the digestive tract, is not easy to be utilized by microorganisms, has low Glycemic Index (GI), and can not obviously increase the blood sugar concentration after being ingested, and the main component stevioside can achieve the purpose of reducing the blood sugar by promoting the release of insulin, and is used for the adjuvant treatment of type II diabetes.
Steviol glycosides and phloretin have many common advantages: can be added into food, and has high safety and blood sugar lowering effect.
In the current research, common technologies for solubilizing phloretin include microemulsion, self-microemulsion, embedding of cyclodextrin and its derivatives, solid dispersion technology and the like. However, these preparation methods are relatively complex and have a small application range, and most of them cannot be applied to the food field. For example, the preparation of phloretin microemulsions and self-microemulsions requires the use of a certain amount of synthetic surfactant, increasing their toxic side effects; the cyclodextrin inclusion technology has low inclusion rate and poor technical stability, and seriously influences the solubilization effect. Solid dispersion technology, while simple to prepare, most of the carriers currently used cannot be added to food.
At present, stevioside is not used as a carrier material of a solid dispersion, and reports on the use of the stevioside for solubilizing phloretin are not available.
Disclosure of Invention
The invention aims to overcome the technical defects in the prior art, and provides a phloretin solubilized solid dispersion with stevioside as a carrier and a preparation method thereof, so as to solve the technical problem of extremely low phloretin solubility in the prior art.
The invention also aims to solve the other technical problems of complex formula and complex process of the conventional solubilization method for phloretin.
The invention also aims to solve the technical problem that phloretin modified products obtained by the conventional solubilization method cannot be applied to food.
The invention also aims to solve the technical problem that the solubilizing effect of the conventional solubilizing method on phloretin needs to be improved.
In order to achieve the technical purpose, the invention adopts the following technical scheme:
the phloretin solubilized solid dispersion with stevioside as a carrier takes stevioside as a carrier and phloretin as a dispersoid.
Preferably, the stevioside accounts for 0-81.6% by mass, and the rebaudioside A accounts for 10.2-98.6% by mass.
Preferably, the stevioside accounts for 0-97.5% by mass, and the rebaudioside A accounts for 0-98.6% by mass.
Preferably, the phloretin in the solid dispersion is 4.94-5.66% by mass.
On the basis of the technical scheme, the invention further provides a preparation method of the phloretin solubilized solid dispersion with stevioside as a carrier, which comprises the following steps:
1) respectively taking stevioside and phloretin in formula amounts, and uniformly mixing to obtain a mixture;
2) mixing the mixture obtained in the step 1) with 95% ethanol, and then carrying out ultrasonic treatment at the frequency of 40KHz until the mixture is completely dissolved;
3) stirring the product obtained in step 2) at a speed of 200rpm (so that the dissolved mixture is uniformly dispersed in the solution);
4) drying the stirred product in the step 3) at 40 ℃ for 30min (to remove most of ethanol to obtain viscous fluid);
5) drying the product dried in the step 4) at 40 ℃ for 6h in vacuum (to remove residual water and ethanol to obtain a white solid);
6) grinding and sieving the product obtained in the step 5), and collecting powder with the particle size of less than 80 meshes to obtain the phloretin solubilizing solid dispersion with stevioside as a carrier.
Preferably, in step 2), the ratio of the mixture to 95% ethanol is: each 500-600 mg of the mixture corresponds to 10mL of 95% ethanol.
Preferably, in the step 2), the duration of the ultrasonic treatment is 5-15 min.
Preferably, the stirring in step 3) is performed by using a magnetic stirring device.
Preferably, in step 3), the product obtained in step 2) is stirred at 200rpm to uniformly disperse the dissolved mixture in the solution.
On the basis of the technical scheme, the invention further provides the application of the phloretin solubilized solid dispersion taking stevioside as a carrier as an oral liquid additive or a beverage additive.
The invention provides a phloretin solubilized solid dispersion with stevioside as a carrier and a preparation method thereof. The technical scheme is characterized in that stevioside is used as a carrier, phloretin is used as a dispersoid, the preparation method is carried out through a solvent method, and 26-30 mg of phloretin can be completely solubilized in water per 500mg of stevioside. The solid dispersion can effectively improve the solubility and the release degree of phloretin, and simultaneously solves the problems of complex formula, complex process, inapplicability to food and the like in the conventional solubilization technology; the method has simple and safe process and low requirement on equipment, and is suitable for industrial-level large-scale production; besides, stevioside and phloretin are both additives suitable for blood sugar-reducing foods and can be used in various food water systems.
The technical advantages of the invention are focused on the following aspects:
1. the phloretin in the solid dispersion with the stevioside as the carrier material exists in an amorphous state, the phloretin in the form can be dissolved in water under less energy input, so that the solubility of the insoluble phloretin is obviously improved, the insoluble phloretin can be fully released in gastric juice and intestinal juice, the bioavailability of the phloretin can be improved, and the phloretin and the stevioside are food additives allowed in GB 2760 food additive use hygienic standard, so that the application of the phloretin in food and beverage is realized.
2. In the prior art, insoluble substances are solubilized by utilizing the characteristic that stevioside is respectively assembled into micelles, and under the solubilization method, the stevioside prevents the combination of phloretin and bioactive protein and limits the exertion of the bioactivity of the phloretin in a human body. According to the method, phloretin is dispersed in stevioside in an amorphous state, most of phloretin in the form can be directly dissolved in water, is not wrapped by stevioside, and can be directly contacted with a plurality of bioactive proteins such as glucosidase, SGLT1, GLUT2 and serum albumin to play a role.
3. The solid dispersion combines the natural sweetening agent stevioside and the glucose absorption inhibitor phloretin, can be used as an additive of hypoglycemic food, provides good raw materials for development of sugar-free food suitable for people with diabetes, and has good social value and application prospect.
4. Compared with the existing phloretin solubilization methods such as cyclodextrin and cyclodextrin derivative inclusion, chemical modification, microemulsion, self-microemulsion, microemulsion gel, cocrystallization, nanofiber and the like, the raw materials adopted by the invention can be safely eaten, the preparation method is short in process and strong in operability, popularization and industrialization are facilitated, and the obtained product can be widely applied to the fields of oral medicines and food and beverages.
Drawings
FIG. 1 is a graph showing the results of comparing the solubilizing abilities of phloretin-solubilized solid dispersion, physical mixture A and pure phloretin using stevioside containing 97.5% stevioside as a carrier material in accordance with an embodiment of the present invention;
FIG. 2 is a graph comparing the solubilization capacities of phloretin solubilized solid dispersion, physical mixture B and pure phloretin with steviol glycosides, containing 81.6% stevioside and 10.2% rebaudioside A, as carrier materials in accordance with an embodiment of the present invention;
FIG. 3 is a graph comparing the solubilization capacities of phloretin solubilized solid dispersion, physical mixture C and pure phloretin with steviol glycosides with 72.5% stevioside and 20.8% rebaudioside A as carrier materials in accordance with an embodiment of the present invention;
FIG. 4 is a graph comparing the solubilization capacities of phloretin solubilized solid dispersion, physical mixture D and pure phloretin with steviol glycosides, containing 60.5% stevioside and 30.2% rebaudioside A, as carrier materials in accordance with an embodiment of the invention;
FIG. 5 is a graph comparing the solubilization capacities of phloretin solubilized solid dispersion, physical mixture E and pure phloretin with steviol glycosides, containing 51.2% stevioside and 40.2% rebaudioside A, as carrier materials in an embodiment of the invention;
FIG. 6 is a graph comparing the solubilization capacities of phloretin solubilized solid dispersion, physical mixture F and pure phloretin with steviol glycosides, 40.2% stevioside and 50.4% rebaudioside A, as carrier materials, in accordance with an embodiment of the invention;
FIG. 7 is a graph comparing the solubilization capacities of phloretin solubilized solid dispersion, physical mixture G and pure phloretin with steviol glycosides, 30.6% stevioside and 61.1% rebaudioside A as carrier materials in accordance with an embodiment of the invention;
FIG. 8 is a graph comparing the solubilization capacities of phloretin solubilized solid dispersion, physical mixture H and pure phloretin with steviol glycosides with 22.1% stevioside and 72.5% rebaudioside A as carrier materials in accordance with an embodiment of the invention;
FIG. 9 is a graph comparing the solubilization capacities of phloretin solubilized solid dispersion, physical mixture K and pure phloretin with steviol glycosides, containing 9.1% stevioside and 80.5% rebaudioside A as carrier materials in accordance with an embodiment of the invention;
FIG. 10 is a graph comparing the solubilization capacities of phloretin-solubilized solid dispersion M, physical mixtures, and pure phloretin with steviol glycosides, with 0% stevioside and 98.6% rebaudioside A as carrier materials in accordance with an embodiment of the invention;
FIG. 11 is an X-ray diffraction pattern of phloretin-solubilized solid dispersion with steviol glycoside containing 97.5% stevioside as a carrier material, steviol glycoside containing 97.5% stevioside, physical mixture A and pure phloretin in an embodiment of the invention;
FIG. 12 is a graph of the in vitro cumulative release of phloretin from physical mixture A and pure phloretin in various release media using a steviol glycoside with 97.5% stevioside as the carrier material versus time for the particular embodiment of the invention;
fig. 13 is a Stern-Volmer relationship diagram of fluorescence quenching of bovine serum albumin by phloretin solubilized solid dispersion, physical mixture a and pure phloretin using stevioside containing 97.5% stevioside as a carrier material in the embodiment of the invention.
Detailed Description
Hereinafter, specific embodiments of the present invention will be described in detail. Well-known structures or functions may not be described in detail in the following embodiments in order to avoid unnecessarily obscuring the details. Approximating language, as used herein in the following examples, may be applied to identify quantitative representations that could permissibly vary in number without resulting in a change in the basic function. Unless defined otherwise, technical and scientific terms used in the following examples have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
Example 1
The phloretin solubilized solid dispersion with steviol glycoside as carrier material was prepared according to the following steps:
s1, weighing 500mg of stevioside containing 97.5% of stevioside and excessive phloretin (about 50mg), and uniformly mixing to obtain a physical mixture A;
s2, adding 10mL of 95% ethanol into the mixture A, and carrying out ultrasonic treatment on the mixture A for about 5min by using 40KHz to completely dissolve the mixture into the ethanol to obtain a solution;
s3, putting the solution at 200 r.min-1Under magnetic stirring, uniformly dispersing the dissolved mixture A in the solution;
s4, drying the solution at 40 ℃ for 30min, and removing most of ethanol to obtain viscous fluid;
s5, vacuum drying the viscous fluid at 40 ℃ for 6 hours, and removing residual water and ethanol to obtain a white solid;
s6, fully grinding and sieving the white solid of S5, and collecting powder with the particle size of below 80 meshes.
550mg of the powder described in S6, 550mg of mixture A and 50mg of phloretin were weighed into a screw sample bottle, 10mL of distilled water was added and stirred for 30min to sufficiently dissolve and equilibrate, and then the solution was centrifuged at 5000rpm for 10min to compare the solubility of phloretin in the supernatant.
As shown in fig. 1, in the solid dispersion with steviol glycoside containing 97.5% stevioside as the carrier material, the solubility of phloretin was 1.98 times that of physical mixture a and 26.26 times that of pure phloretin. 30.38mg of phloretin can be completely solubilized by every 500mg of stevioside containing 97.5% of stevioside, namely, the mass percentage of the phloretin which can be loaded by the stevioside containing 97.5% of stevioside is 5.73%.
Example 2
Unlike example 1, a solid dispersion and physical mixture B were prepared using a steviol glycoside comprising 81.6% stevioside and 10.2% rebaudioside a, with sonication time about 6 min.
550mg of the solid dispersion powder, 550mg of the mixture B and 50mg of phloretin were weighed in a screw sample bottle, 10mL of distilled water was added and stirred for 10min to dissolve sufficiently, and then the solution was centrifuged at 5000rpm for 10min to compare the solubility of phloretin in the supernatant.
As shown in fig. 2, in the solid dispersion with steviol glycoside, which contains 81.6% stevioside and 10.2% rebaudioside a, as carrier material, the solubility of phloretin was 1.98 times that of physical mixture B and 26.23 times that of pure phloretin. 30.34mg of phloretin can be completely solubilized by every 500mg of stevioside containing 81.6% of stevioside and 10.2% of rebaudioside A, namely, the mass percentage of the phloretin which can be loaded by the stevioside containing 81.6% of stevioside and 10.2% of rebaudioside A is 5.72%.
Example 3
Unlike example 1, a solid dispersion and physical mixture C were prepared using a steviol glycoside comprising 72.5% stevioside and 20.8% rebaudioside a, with sonication time about 7 min.
550mg of the solid dispersion powder, 550mg of the mixture C and 50mg of phloretin were weighed in a screw sample bottle, 10mL of distilled water was added and stirred for 10min to dissolve sufficiently, and then the solution was centrifuged at 5000rpm for 10min to compare the solubility of phloretin in the supernatant.
As shown in fig. 3, in the solid dispersion with stevioside containing 72.5% stevioside and 20.8% rebaudioside a as the carrier material, the solubility of phloretin was 2.00 times that of physical mixture C and 26.16 times that of pure phloretin. 30.26mg of phloretin can be completely solubilized by every 500mg of stevioside containing 72.5% of stevioside and 20.8% of rebaudioside A, namely, the mass percentage of the phloretin which can be loaded by the stevioside containing 72.5% of stevioside and 20.8% of rebaudioside A is 5.71%.
Example 4
Unlike example 1, a solid dispersion and physical mixture D were prepared using a steviol glycoside comprising 60.5% stevioside and 30.2% rebaudioside a, with sonication time about 8 min.
550mg of the solid dispersion powder, 550mg of the mixture D and 50mg of phloretin were weighed in a screw sample bottle, 10mL of distilled water was added and stirred for 10min to dissolve sufficiently, and then the solution was centrifuged at 5000rpm for 10min to compare the solubility of phloretin in the supernatant.
As shown in fig. 4, in the solid dispersion with steviol glycoside containing 60.5% stevioside and 30.2% rebaudioside a as carrier material, the solubility of phloretin was 2.00 times that of physical mixture D and 25.93 times that of pure phloretin. Every 500mg of stevioside containing 60.5% of stevioside and 30.2% of rebaudioside A can completely solubilize 30.99mg of phloretin, namely, the mass percentage of the phloretin which can be loaded by the stevioside containing 60.5% of stevioside and 30.2% of rebaudioside A is 5.66%.
Example 5
Unlike example 1, a solid dispersion and physical mixture E were prepared using a steviol glycoside comprising 51.2% stevioside and 40.2% rebaudioside a, with a sonication time of about 9 min.
550mg of the solid dispersion powder, 550mg of the mixture E and 50mg of phloretin were weighed in a screw sample bottle, 10mL of distilled water was added and stirred for 10min to dissolve sufficiently, and then the solution was centrifuged at 5000rpm for 10min to compare the solubility of phloretin in the supernatant.
As shown in fig. 5, in the solid dispersion with steviol glycoside, 51.2% stevioside and 40.2% rebaudioside a as carrier material, the solubility of phloretin was 2.01 times that of physical mixture E and 25.70 times that of pure phloretin. Every 500mg of stevioside containing 51.2% of stevioside and 40.2% of rebaudioside A can completely solubilize 29.73mg of phloretin, namely, the mass percentage of the phloretin which can be loaded by the stevioside containing 51.2% of stevioside and 40.2% of rebaudioside A is 5.61%.
Example 6
Unlike example 1, a solid dispersion and physical mixture F were prepared using a steviol glycoside comprising 40.2% stevioside and 50.4% rebaudioside a, with sonication time about 10 min.
550mg of the solid dispersion powder, 550mg of the mixture F and 50mg of phloretin were weighed in a screw sample bottle, 10mL of distilled water was added and stirred for 10min to dissolve sufficiently, and then the solution was centrifuged at 5000rpm for 10min to compare the solubility of phloretin in the supernatant.
As shown in fig. 6, in the solid dispersion with steviol glycoside, 40.2% stevioside and 50.4% rebaudioside a, as carrier material, phloretin was 2.00 times more soluble than physical mixture F and 25.65 times more soluble than pure phloretin. Every 500mg of stevioside containing 40.2% stevioside and 50.4% rebaudioside A can be completely solubilized to 29.67mg phloretin, i.e., the mass percentage of phloretin that can be loaded by stevioside containing 40.2% stevioside and 50.4% rebaudioside A is 5.60%.
Example 7
Unlike example 1, a solid dispersion and physical mixture G was prepared using a steviol glycoside comprising 30.6% stevioside and 61.1% rebaudioside a, with a sonication time of about 11 min.
550mg of the solid dispersion powder, 550mg of the mixture G and 50mg of phloretin were weighed in a screw sample bottle, 10mL of distilled water was added and stirred for 10min to dissolve sufficiently, and then the solution was centrifuged at 5000rpm for 10min to compare the solubility of phloretin in the supernatant.
As shown in fig. 7, in the solid dispersion with steviol glycoside containing 30.6% stevioside and 61.1% rebaudioside a as carrier material, the solubility of phloretin was 2.01 times that of physical mixture G and 25.58 times that of pure phloretin. Every 500mg of stevioside containing 30.6% of stevioside and 61.1% of rebaudioside A can completely solubilize 29.60mg of phloretin, namely, the mass percentage of the phloretin which can be loaded by the stevioside containing 30.6% of stevioside and 61.1% of rebaudioside A is 5.59%.
Example 8
Unlike example 1, a solid dispersion and physical mixture H were prepared using a steviol glycoside comprising 22.1% stevioside and 72.5% rebaudioside a, with sonication time about 12 min.
550mg of the solid dispersion powder, 550mg of the mixture H and 50mg of phloretin were weighed in a screw sample bottle, 10mL of distilled water was added and stirred for 10min to dissolve sufficiently, and then the solution was centrifuged at 5000rpm for 10min to compare the solubility of phloretin in the supernatant.
As shown in fig. 8, in the solid dispersion with steviol glycoside, 22.1% stevioside and 72.5% rebaudioside a as carrier material, the solubility of phloretin was 1.97 times that of physical mixture H and 25.12 times that of pure phloretin. Every 500mg of stevioside containing 22.1% of stevioside and 72.5% of rebaudioside A can be completely solubilized to obtain 29.06mg of phloretin, namely, the mass percentage of the phloretin which can be loaded by the stevioside containing 22.1% of stevioside and 72.5% of rebaudioside A is 5.49%.
Example 9
Unlike example 1, a solid dispersion and a physical mixture K were prepared using steviol glycosides, containing 9.1% stevioside and 80.5% rebaudioside a, with a sonication time of about 14 min.
550mg of the solid dispersion powder, 550mg of the mixture K and 50mg of phloretin were weighed in a screw sample bottle, 10mL of distilled water was added and stirred for 10min to dissolve sufficiently, and then the solution was centrifuged at 5000rpm for 10min to compare the solubility of phloretin in the supernatant.
As shown in fig. 9, in the solid dispersion with steviol glycoside, which contains 9.1% stevioside and 80.5% rebaudioside a, as carrier material, the solubility of phloretin was 1.94 times that of physical mixture K and 24.61 times that of pure phloretin. 28.47mg of phloretin can be completely solubilized by every 500mg of stevioside containing 9.1% of stevioside and 80.5% of rebaudioside A, namely, the mass percentage of the phloretin which can be loaded by the stevioside containing 9.1% of stevioside and 80.5% of rebaudioside A is 5.39%.
The phloretin solubilized solid dispersion aqueous solution using stevioside containing 9.1% stevioside and 80.5% rebaudioside a as a carrier material showed white flocculent precipitates after long-term storage, and had poor stability.
Example 10
Unlike embodiment 1, a solid dispersion and a physical mixture L were prepared using stevioside containing 0% stevioside and 98.6% rebaudioside a, with a sonication time of about 15 min.
550mg of the solid dispersion powder, 550mg of the mixture L and 50mg of phloretin were weighed in a screw sample bottle, 10mL of distilled water was added and stirred for 10min to dissolve sufficiently, and then the solution was centrifuged at 5000rpm for 10min to compare the solubility of phloretin in the supernatant.
As shown in fig. 10, in the solid dispersion with steviol glycoside containing 0% stevioside and 98.6% rebaudioside a as carrier material, the solubility of phloretin was 2.02 times that of physical mixture L and 23.05 times that of pure phloretin. 26.67mg of phloretin can be completely solubilized by every 500mg of stevioside containing 0% stevioside and 98.6% rebaudioside A, namely, the mass percentage of the phloretin loaded by the stevioside containing 0% stevioside and 98.6% rebaudioside A is 5.06%.
The phloretin solubilized solid dispersion aqueous solution using stevioside containing 0% stevioside and 98.6% rebaudioside a as a carrier material showed white flocculent precipitates after long-term storage, and had poor stability.
Example 11 (phloretin solubilized solid dispersion X-ray diffraction experiment with steviol glycoside as carrier Material)
1. Test sample
Phloretin solubilized solid dispersion using stevioside containing 97.5% stevioside as carrier material, stevioside containing 97.5% stevioside, physical mixture A and phloretin
2. Experimental methods
Respectively analyzing the sample powder by adopting an X-ray diffractometer under the test condition of a Cu-Ka target; the tube voltage is 40 KV; the tube current was 30 mA; the scanning speed is 8 DEG/min-1(ii) a The step length is 0.02; the diffraction angle scanning range is 5-50 degrees; the divergence slit is 1 degree; the anti-scatter slit is 1 degree; the receiving slit is 0.03 mm.
3. Results
As shown in fig. 11. Phloretin exhibits characteristic diffraction peaks at 2 θ values of 6.9 °, 9.5 °, 19.1 °, 27.1 ° and 28 °, respectively, whereas steviol glycosides do not exhibit any peaks over the test range of 5 ° to 50 °. Physical mixture a showed the same diffraction pattern as PT, but the signal was weaker due to the dilution effect of steviol glycosides. In the solid dispersion, the characteristic diffraction pattern of phloretin disappeared, indicating that phloretin had been converted from the crystalline state to the amorphous state. The phloretin in the form can be directly dissolved into water only by a small amount of energy, so that the solubility of the phloretin is increased.
Example 12 (phloretin solubilized solid dispersion with steviol glycoside as carrier Material in vitro Release test)
The in vitro release experiments were performed using a reverse dialysis bag method.
1. Test sample
Phloretin solubilized solid dispersion with stevioside containing 97.5% of stevioside as carrier material, physical mixture A and phloretin
2. Experimental methods
Artificial intestinal juice (SIF) and artificial gastric juice (SGF) were prepared according to the "Chinese pharmacopoeia" 2015 edition.
Adding 2mL of SGF or SIF into dialysis bag boiled in boiling water for 10min, and fastening the bag. The dialysis bag was placed in a triangular flask containing 100mL of SGF or SIF, and the test sample powder was added to the flask. Each bottle is respectively provided with 8 dialysis bags, the temperature is controlled to be 37 +/-0.5 ℃, the rotating speed is controlled to be 100r/min, 1 dialysis bag is taken out at a certain time interval for analysis, and simultaneously 2mL of release medium with the same temperature is supplemented.
The cumulative release is the total amount of the substance to be tested released by the system in t time, and is calculated by the following formula:
Mt＝VCt+∑C t-1Vsample (A)
Wherein M istCumulative release for the t time system; ctThe release concentration of phloretin at the time of sampling at t time, and V is the volume before sampling, which is 100mL in the experiment; ct-1Sampling the concentration of the previous sampling time point for the time t; vSample (A)For each sample volume taken, it was 2mL in this experiment.
3. Results
As shown in FIG. 12, in SGF at pH1.2, the cumulative amount of phloretin released in the solid dispersion over 36 hours was 1.3 times higher than that of physical mixture A and 9.2 times higher than that of pure phloretin. The cumulative amount of phloretin released in the solid dispersion over 36 hours was 2.4 times higher than that of pure calcareous dermatan in SIF ph6.8, but lower than that of physical mixture a. This is because phloretin is unstable in a slightly alkaline environment, and solubilized phloretin has a large contact area with SIF, and phloretin in a solid dispersion degrades rapidly in SIF. In general, the solid dispersion with stevioside as a carrier material remarkably improves the release amount of phloretin in gastrointestinal fluid.
Example 13 (interaction experiment of phloretin solubilized solid dispersion with steviol glycoside as carrier material and bovine serum albumin)
1. Test sample
Phloretin solubilized solid dispersion with stevioside containing 97.5% of stevioside as carrier material, physical mixture A and phloretin
2. Experimental methods
1mL each of the aqueous solid dispersion solution containing phloretin at 3mg/mL, the aqueous physical mixture A solution and the phloretin ethanol solution was taken up and diluted with distilled water to 100mL so that the final concentration of phloretin in each system was 0.03 mg/mL.
And (3) researching the interaction condition between the bovine serum albumin and phloretin in different systems by adopting fluorescence spectroscopy. 4mL of pH 7.4Tris-HCl buffer solution, 2mL of 10 mu g/mL BSA solution, 2mL of 0.05mol/L NaCl solution and sample solutions with different amounts are sequentially added into a colorimetric tube, the volume is determined to be 10mL by distilled water, and the mixture is shaken up and then kept stand for 20 min.
Test conditions for fluorescence spectrum scanning: the excitation wavelength is 280nm, the widths of the excitation slit and the emission slit are respectively 2.5 nm and 5nm, the emission wavelength range is 290 nm-450 nm, and the fluorescence value of about 340nm is recorded.
3. Results
As shown in FIG. 13, the quenching rate (K) of pure phloretin for bovine serum albuminsv) The highest binding to bovine serum albumin was suggested. Compared with pure phloretin, the quenching rate of phloretin in the physical mixture A to bovine serum albumin is obviously reduced, because phloretin is wrapped by stevioside self-assembled micelles in aqueous solution to block the interaction of phloretin and bovine serum albumin. The quenching rate of phloretin in the solid dispersion on bovine serum albumin is almost the same as that of pure phloretin. It can be seen that after the solid dispersion is dissolved in water, the dissolution state of most phloretin is close to that of a pure phloretin solution, and the interaction between the phloretin and bioactive protein is facilitated to play the bioactivity.
The embodiments of the present invention have been described in detail, but the description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention. Any modification, equivalent replacement, and improvement made within the scope of the application of the present invention should be included in the protection scope of the present invention.
Claims (7)
1. Phloretin solubilization solid dispersion with stevioside as a carrier is characterized in that the solid dispersion takes stevioside as a carrier and phloretin as a dispersoid; the stevioside accounts for 22.1-97.5% by mass, the rebaudioside A accounts for 0-72.5% by mass, and the phloretin accounts for 4.94-5.66% by mass in the solid dispersion.
2. The method of preparing a phloretin-solubilized solid dispersion with steviol glycoside as a carrier in claim 1, comprising the steps of:
1) respectively taking stevioside and phloretin in formula amounts, and uniformly mixing to obtain a mixture;
2) mixing the mixture obtained in the step 1) with 95% ethanol, and then carrying out ultrasonic treatment at the frequency of 40KHz until the mixture is completely dissolved;
3) stirring the product obtained in the step 2) at the rotating speed of 200 rpm;
4) drying the product stirred in the step 3) at 40 ℃ for 30 min;
5) carrying out vacuum drying on the product dried in the step 4) at the temperature of 40 ℃ for 6 hours;
6) grinding and sieving the product obtained in the step 5), and collecting powder with the particle size of less than 80 meshes to obtain the phloretin solubilizing solid dispersion with stevioside as a carrier.
3. The method according to claim 2, wherein in step 2), the ratio of the mixture to 95% ethanol is: each 500-600 mg of the mixture corresponds to 10mL of 95% ethanol.
4. The preparation method according to claim 2, wherein in the step 2), the duration of the ultrasonic treatment is 5 to 15 min.
5. The method according to claim 2, wherein the stirring in step 3) is performed by a magnetic stirring apparatus.
6. The method according to claim 2, wherein in the step 3), the product obtained in the step 2) is stirred at 200rpm to uniformly disperse the dissolved mixture in the solution.
7. Use of the phloretin-solubilized solid dispersion of claim 1 with steviol glycoside as carrier in the preparation of an oral liquid additive or a beverage additive.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910948738.3A CN110538145B (en) | 2019-10-08 | 2019-10-08 | Phloretin solubilization solid dispersion with stevioside as carrier and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910948738.3A CN110538145B (en) | 2019-10-08 | 2019-10-08 | Phloretin solubilization solid dispersion with stevioside as carrier and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110538145A CN110538145A (en) | 2019-12-06 |
| CN110538145B true CN110538145B (en) | 2021-10-22 |
Family
ID=68715599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910948738.3A Active CN110538145B (en) | 2019-10-08 | 2019-10-08 | Phloretin solubilization solid dispersion with stevioside as carrier and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110538145B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104530448A (en) * | 2014-12-16 | 2015-04-22 | 江南大学 | Method for preparing high-solubility stevioside compound |
| CN105362229A (en) * | 2015-11-19 | 2016-03-02 | 五邑大学 | Water-soluble phloretin solid dispersion and preparation method thereof |
| CN108014104A (en) * | 2018-01-22 | 2018-05-11 | 青岛科技大学 | A kind of Synergistic type dihydromyricetin soluble type compound and preparation method thereof |
-
2019
- 2019-10-08 CN CN201910948738.3A patent/CN110538145B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104530448A (en) * | 2014-12-16 | 2015-04-22 | 江南大学 | Method for preparing high-solubility stevioside compound |
| CN105362229A (en) * | 2015-11-19 | 2016-03-02 | 五邑大学 | Water-soluble phloretin solid dispersion and preparation method thereof |
| CN108014104A (en) * | 2018-01-22 | 2018-05-11 | 青岛科技大学 | A kind of Synergistic type dihydromyricetin soluble type compound and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| Novel self-nanomicellizing solid dispersion based on rebaudioside A: a potential nanoplatform for oral delivery of curcumin;Yuzhen Hou等;《International Journal of Nanomedicine》;20190111(第14期);第557-571页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110538145A (en) | 2019-12-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109303922B (en) | Rosa roxburghii polysaccharide functionalized nano-selenium compound, preparation method thereof and application thereof in hypoglycemic drugs | |
| JP4606444B2 (en) | Anthocyanin-containing composition for oral administration and method for producing the same | |
| KR100450097B1 (en) | Compositions of plant carbohydrates as dietary supplements | |
| EP1113791A2 (en) | Bioflavonoid as blood glucose level lowering agent | |
| BR112021000917A2 (en) | COMPOSITION AND METHODS TO GENERATE AND SUPPORT MOLECULAR HYDROGEN (H2) IN AQUEOUS SYSTEMS | |
| CN113647624B (en) | Preparation method of curcumin microcapsule | |
| CN105007759A (en) | Metal ion-functional fiber component complex compositions, preparation and uses thereof | |
| DE102013011026A1 (en) | Composition of a food additive | |
| TW201216972A (en) | Metal ion nanoclusters | |
| CN110140958A (en) | A kind of astaxanthin oral solution and preparation method thereof | |
| CN104800240B (en) | A kind of preparation method of nanometer selenium-luxuriant mushroom polysaccharide composite body of shuttle handle pine | |
| Li et al. | Cannabidiol/hydroxypropyl-β-cyclodextrin inclusion complex: Structure analysis, release behavior, permeability, and bioactivity under in vitro digestion | |
| CN110538145B (en) | Phloretin solubilization solid dispersion with stevioside as carrier and preparation method thereof | |
| Zannou et al. | Nanoencapsulation of Cyanidin 3-O-Glucoside: Purpose, technique, bioavailability, and stability | |
| CN113208111A (en) | Preparation method of betacyanin microcapsule with composite wall material | |
| Ribeiro et al. | Cashew apple pectin as a carrier matrix for mangiferin: Physicochemical characterization, in vitro release and biological evaluation in human neutrophils | |
| Li et al. | Characterizations of food-derived ellagic acid-Undaria pinnatifida polysaccharides solid dispersion and its benefits on solubility, dispersity and biotransformation of ellagic acid | |
| JP2006104181A (en) | Glucide-splitting enzyme-inhibiting material derived from fagaceae plant and application thereof | |
| CN116019187A (en) | Anti-glycation composition of natural source, preparation method and application in oral cosmetic product | |
| JP5948871B2 (en) | Polyphenol-containing composition | |
| JP4896401B2 (en) | Ursolic acid-soybean lecithin freeze-dried nanoparticle injection and method for producing the same | |
| CN114271492A (en) | High-content rutin powder raw material composition, rutin powder, and preparation method and application thereof | |
| Geng et al. | Effects of different extraction methods on the physico-chemical characteristics and biological activities of polysaccharides from Clitocybe squamulosa | |
| CN114259515A (en) | Composition with anti-saccharification effect and application | |
| JP2016067300A (en) | Beverage composition and method of producing beverage composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |