CN111869880B - Carnitine sustained-release preparation and preparation method thereof - Google Patents
Carnitine sustained-release preparation and preparation method thereof Download PDFInfo
- Publication number
- CN111869880B CN111869880B CN202010776143.7A CN202010776143A CN111869880B CN 111869880 B CN111869880 B CN 111869880B CN 202010776143 A CN202010776143 A CN 202010776143A CN 111869880 B CN111869880 B CN 111869880B
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- CN
- China
- Prior art keywords
- carnitine
- whey protein
- sustained
- mechanical shearing
- treatment
- Prior art date
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- 229960004203 carnitine Drugs 0.000 title claims abstract description 50
- 239000003405 delayed action preparation Substances 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 title abstract 10
- 102000007544 Whey Proteins Human genes 0.000 claims abstract description 120
- 108010046377 Whey Proteins Proteins 0.000 claims abstract description 120
- 235000021119 whey protein Nutrition 0.000 claims abstract description 120
- 238000010008 shearing Methods 0.000 claims abstract description 73
- 239000002245 particle Substances 0.000 claims abstract description 47
- 238000010438 heat treatment Methods 0.000 claims abstract description 37
- 238000013268 sustained release Methods 0.000 claims abstract description 13
- 239000012730 sustained-release form Substances 0.000 claims abstract description 13
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 claims description 90
- 239000000203 mixture Substances 0.000 claims description 31
- 239000012460 protein solution Substances 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 102000004407 Lactalbumin Human genes 0.000 claims description 16
- 108090000942 Lactalbumin Proteins 0.000 claims description 16
- 102000008192 Lactoglobulins Human genes 0.000 claims description 14
- 108010060630 Lactoglobulins Proteins 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 8
- 235000013861 fat-free Nutrition 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 238000007669 thermal treatment Methods 0.000 claims 1
- 239000008280 blood Substances 0.000 abstract description 10
- 210000004369 blood Anatomy 0.000 abstract description 10
- 235000013305 food Nutrition 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 5
- 239000003381 stabilizer Substances 0.000 abstract description 3
- 235000019463 artificial additive Nutrition 0.000 abstract description 2
- 239000003995 emulsifying agent Substances 0.000 abstract description 2
- 235000012041 food component Nutrition 0.000 abstract description 2
- 239000005417 food ingredient Substances 0.000 abstract description 2
- 239000003205 fragrance Substances 0.000 abstract description 2
- 239000007939 sustained release tablet Substances 0.000 abstract 1
- 239000008187 granular material Substances 0.000 description 24
- 238000000034 method Methods 0.000 description 15
- BQMPVGMHZKZPBH-BYZBDTJCSA-N (3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O.C[N+](C)(C)C[C@H](O)CC([O-])=O BQMPVGMHZKZPBH-BYZBDTJCSA-N 0.000 description 13
- 239000012141 concentrate Substances 0.000 description 12
- 235000008504 concentrate Nutrition 0.000 description 12
- 238000001694 spray drying Methods 0.000 description 11
- 230000000052 comparative effect Effects 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- 239000003925 fat Substances 0.000 description 8
- 235000019197 fats Nutrition 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 5
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- 239000000546 pharmaceutical excipient Substances 0.000 description 5
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- 238000012360 testing method Methods 0.000 description 5
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- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
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- 239000000047 product Substances 0.000 description 3
- 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 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 206010023388 Ketonuria Diseases 0.000 description 2
- 208000007976 Ketosis Diseases 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000011162 core material Substances 0.000 description 2
- 235000013365 dairy product Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000000905 isomalt Substances 0.000 description 2
- 235000010439 isomalt Nutrition 0.000 description 2
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 2
- 238000007561 laser diffraction method Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 235000021243 milk fat Nutrition 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 238000000790 scattering method Methods 0.000 description 2
- 235000020183 skimmed milk Nutrition 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- PHIQHXFUZVPYII-LURJTMIESA-N (S)-carnitine Chemical compound C[N+](C)(C)C[C@@H](O)CC([O-])=O PHIQHXFUZVPYII-LURJTMIESA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- RZALONVQKUWRRY-FYZOBXCZSA-N 2,3-dihydroxybutanedioic acid;(3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound OC(=O)C(O)C(O)C(O)=O.C[N+](C)(C)C[C@H](O)CC([O-])=O RZALONVQKUWRRY-FYZOBXCZSA-N 0.000 description 1
- PVXPPJIGRGXGCY-DJHAAKORSA-N 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@](O)(CO)O1 PVXPPJIGRGXGCY-DJHAAKORSA-N 0.000 description 1
- 241000208140 Acer Species 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 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
- 238000007696 Kjeldahl method Methods 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
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- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 230000009286 beneficial effect 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
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- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
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- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 229940095686 granule product Drugs 0.000 description 1
- 239000008123 high-intensity sweetener Substances 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 229960001518 levocarnitine Drugs 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 201000003694 methylmalonic acidemia Diseases 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000013615 non-nutritive sweetener Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000020939 nutritional additive Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 235000016046 other dairy product Nutrition 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 201000004012 propionic acidemia Diseases 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 201000011296 tyrosinemia Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000001771 vacuum deposition Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
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
- 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
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- 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
- A23L33/17—Amino acids, peptides or proteins
- A23L33/19—Dairy proteins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P10/00—Shaping or working of foodstuffs characterised by the products
- A23P10/40—Shaping or working of foodstuffs characterised by the products free-flowing powder or instant powder, i.e. powder which is reconstituted rapidly when liquid is added
-
- 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
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Health & Medical Sciences (AREA)
- Nutrition Science (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The invention provides a carnitine sustained-release preparation and a preparation method thereof, the sustained-release preparation comprises carnitine and whey protein aggregates, and the mass ratio of the carnitine is as follows: 0.1 to 20wt%, 50% of the whey protein aggregate particles having an average particle diameter of 2 to 10 μm, and at least 30wt% of carnitine being dispersed in the whey protein aggregate particles. The carnitine sustained-release preparation mainly comprises natural food ingredients, can be prepared by simple treatment, namely, the carnitine sustained-release preparation is prepared by simultaneously carrying out heat treatment and mechanical shearing treatment, does not use a pH regulator, is basically free of a stabilizer, an emulsifier and other synthetic additives, has a high natural appearance, has good fragrance and food feeling, is basically free of potential safety hazard, and is particularly suitable for infants; the carnitine sustained-release tablet has the carnitine sustained-release effect, the frequency of use in one day is greatly reduced, and the blood concentration of the carnitine is stable.
Description
Technical Field
The invention relates to the field of sustained-release preparations, in particular to a carnitine sustained-release preparation and a preparation method thereof.
Background
L-carnitine has been used in the fields of medicine, health care, and food, and has been prescribed as a legal multi-purpose nutritional agent by Swiss, france, the United states, and the world health organization. The national food additive sanitary standard GB2760-1996 stipulates that L-carnitine tartrate is a food nutrition enhancer and can be applied to chewable tablets, drinking liquid, capsules, milk powder, milk beverage and the like. And can be used as one of main ingredients of weight-reducing nutritional food.
In particular to the application of L-carnitine in treating diseases of infants, such as canned powder or solution,
-1 infants for type I, II, III tyrosinaemia,
-1, applicable to infants with maple syrup urine,
-1, for benzene [ propane ]]In infants with ketonuria, the infant is likely to suffer from ketonuria,
-1, applicable to infants with propionic or methylmalonic acidemia.
However, L-carnitine is only 1-6 hours after administration, and in addition, a large amount of amino acids cannot be administered simultaneously when administration is performed, which may affect L-carnitine absorption. Therefore, the canned powder or solution can be used for a plurality of times a day, and a large amount of amino acid can not be taken simultaneously when the powder or solution is taken.
Therefore, an L-carnitine preparation which can be slowly released and is suitable for infants is needed in reality.
The following carnitine sustained release formulation technologies are known:
CN109820836A: the L-carnitine sustained-release microcapsule powder and the preparation method thereof comprise the following steps: (1) putting the wall material into ethanol to dissolve and prepare uniform coating liquid I with the solid content of 13 percent; the wall material is a mixture of a slow release retarder and a plasticizer according to the mass ratio of 10-15; (2) coating a core material with a coating liquid I in a fluidized bed, wherein the core material is L-carnitine; the temperature of the materials in the fluidized bed is 43-44 ℃, the air volume is 15-35 m3/h, and the L-carnitine sustained-release microcapsule powder is prepared after 15-20 min of hot baking. The method of the invention can effectively coat the L-carnitine to form a protective layer, isolate the L-carnitine from the external environment, solve the problem of strong hygroscopicity, and simultaneously enable the L-carnitine to have a certain slow release effect to form a microcapsule granule product. The effective content of the L-carnitine in the product is more than 85 percent, the process is simple, and chemical reaction and environmental pollution are not involved.
CN101269039A: the invention aims to supplement the defects of the prior art and provide a sustained-release L-carnitine dropping pill preparation. The sustained-release L-carnitine dropping pill is prepared by adding the stabilizer vitamin E into the components adopted in the prior art, ensures that the medicine does not have obvious change of related substance content in the effective storage period, simultaneously has the advantages of full medicine release, controllable medicine release time and high bioavailability, and is suitable for clinical and household use.
CN101219133A: the invention provides an L-carnitine pellet preparation which is prepared from L-carnitine and pharmaceutic adjuvants and is characterized in that the pharmaceutic adjuvants comprise an excipient and an adhesive, wherein the L-carnitine accounts for 10-90 wt%, the excipient accounts for 20-80 wt%, and the adhesive accounts for 1-5 wt%.
The technology adds too many pharmaceutic adjuvants, which may cause damage to infants and has potential safety hazard, so the technology is not suitable for infants.
Disclosure of Invention
The invention provides a carnitine sustained-release preparation, and aims to provide a carnitine sustained-release preparation suitable for infants.
In order to achieve the above object, the present invention provides a carnitine sustained-release preparation, the components of which comprise carnitine and whey protein aggregate, wherein the carnitine comprises the following components by mass: 0.1 to 20wt%, 50% of the whey protein aggregate particles having an average particle diameter of 2 to 10 μm, and at least 30wt% of carnitine being dispersed in the whey protein aggregate particles.
Preferably, the carnitine is l-carnitine.
Preferably, at least 50wt% of said carnitine is dispersed in said whey protein aggregates.
Preferably, the total content of lactalbumin and lactoglobulin in the whey protein is not less than 40wt%.
Preferably, the content of whey protein aggregates in the sustained release preparation is 5 to 50wt%.
Preferably, the sustained release formulation is low-fat or fat-free or contains air bubbles.
The embodiment of the invention also provides a preparation method of the carnitine sustained-release preparation, which comprises the following steps: adding carnitine and lactalbumin into water, uniformly mixing, simultaneously carrying out heat treatment and mechanical shearing treatment to obtain a lactalbumin solution, and continuing the heat treatment and mechanical shearing treatment to ensure that the solution contains particles with the D50 of 2-10 mu m, thus obtaining the carnitine sustained-release preparation.
Preferably, the heat treatment temperature is 55-100 ℃, and the heating treatment time is 25-60 min.
Preferably, the rotation speed of the mechanical shearing is 100-10000 rpm, and the shearing force is 1.9-190 Pa.
Preferably, the whey protein solution has a pH of 4.5 to 5.0.
The scheme of the invention has the following beneficial effects: the carnitine sustained-release preparation mainly comprises natural food ingredients and can be prepared by simple treatment, namely, by simultaneously carrying out heat treatment and mechanical shearing treatment, a pH regulator can be not used, and the carnitine sustained-release preparation is basically free of a stabilizer, an emulsifier and other synthetic additives, has a product with a high natural appearance, has good fragrance and food feeling, is basically free of potential safety hazard, and is particularly suitable for infants; the carnitine has good slow release effect, the frequency of use in one day is greatly reduced, and the blood concentration of the carnitine is stable.
Detailed Description
In order to make the technical problems, technical solutions and advantages to be solved by the present invention clearer, the following detailed description will be given with specific embodiments.
The carnitine of the present invention includes biologically active L-carnitine, as well as its non-biologically active enantiomer, D-carnitine. L-carnitine (L-carnitine) is preferred. The components of the sustained-release preparation comprise carnitine and whey protein aggregate, and the carnitine sustained-release emulsion contains 0.1-20 wt% of carnitine, preferably 0.5-10 wt% of carnitine, more preferably 1-5 wt% of carnitine, and at least 30wt% of carnitine is dispersed in the whey protein aggregate particles.
Preferably, the carnitine is dispersed in the whey protein aggregate in an amount of at least 50wt%, more preferably in an amount of 50 to 80 wt%.
Preferably, the carnitine sustained release preparation comprises 5-50 wt% of whey protein aggregates, more preferably 6-30 wt% of whey protein aggregates, and most preferably 8-15 wt% of whey protein aggregates.
Preferably, the carnitine sustained-release preparation further comprises a nutritional additive.
Preferably, the carnitine sustained release formulation is low-fat or defatted.
Preferably, the carnitine sustained-release preparation comprises air bubbles.
The whey protein used in the present invention has a total content of lactalbumin and lactoglobulin of not less than 40wt%, preferably not less than 60wt%, more preferably not less than 80wt%, and a high content of lactalbumin and lactoglobulin which facilitates the aggregation reaction of whey protein under heat and the inclusion of carnitine by the above-mentioned whey protein aggregates.
The protein content of the above whey protein solution may be 0.5 to 60wt%, preferably 1 to 40wt%, 2.5 to 20wt%, still more preferably 3 to 10wt%, still more preferably 3 to 5 wt%. For example, the protein content may be calculated based on known information, or may be calculated by measurement according to a known or commonly used method such as the Kjeldahl method.
The whey protein solution may further contain lactose, wherein the ratio of the mass (concentration) of the protein content to the mass (concentration) of the lactose is preferably 1-9: 9-1, more preferably 2-6: 8-4. The lactose content can be calculated here on the basis of known information or can be calculated after measurement according to known or customary methods, for example liquid chromatography or enzyme kits. When the protein content is higher than the lactose content, the yield of whey protein aggregates per unit decreases. On the other hand, whey protein aggregation to produce aggregates can occur rapidly when the lactose content is higher than the protein content.
The heat treatment used in the present invention may be performed by any method without particular limitation, provided that the heat treatment may be performed simultaneously with the mechanical shearing treatment. For example, general heat treatment equipment suitable for food processing techniques may be used. Comprises a jacket tank, a plate heat exchanger, a tube heat exchanger, a scraper type heat exchanger, a steam jet type heater and an electric heater. The heat treatment temperature may be 55 ℃ or more, preferably 55 to 100 ℃, more preferably 70 to 90 ℃, still more preferably 75 to 85 ℃, still more preferably 75 to 80 ℃. When the heat treatment temperature is 75 to 85 ℃, the heat treatment time may be 25 to 60 minutes, preferably 25 to 40 minutes, and more preferably 25 to 30 minutes.
The mechanical shearing treatment may be carried out by any method in the present invention, and is not particularly limited, provided that the shearing treatment may be carried out simultaneously with the heating treatment. For example, general mechanical shear processing equipment suitable for food processing techniques may be used. Such equipment includes a turbo mixer (manufactured by Scanima) and a homomixer (manufactured by PRIMIX corporation). Regarding the shearing force in the mechanical shearing treatment, for example, from the viewpoint of avoiding too small a diameter, when a homomixer (t.k. Homo MIXER MARKII, model 2.5, manufactured by PRIMIX corporation) is used, the rotation speed may be 100 to 10000rpm, preferably 200 to 8000rpm, more preferably 250 to 5000rpm. The rotation speeds of the homomixer, namely 100 to 10000rpm, 200 to 8000rpm and 250 to 5000rpm, are respectively equivalent to 1.9 to 190Pa, 3.7 to 150Pa and 4.7 to 94Pa of the shearing force (shear stress). That is, the shearing force in the mechanical shearing treatment may be 1.9 to 190Pa, preferably 3.7 to 150Pa, and more preferably 4.7 to 94Pa. Since the shearing force in the mechanical shearing treatment is obviously changed depending on the type (model) setting and capacity (operating condition) of the shearing treatment apparatus actually used, a person skilled in the art can achieve the effect of the present invention by appropriately changing the model, the operating condition, and the like.
The expression "whey protein aggregate" as used herein means a particle aggregate consisting mainly of whey protein and obtained by subjecting a whey protein solution to a simultaneous heating treatment and mechanical shearing treatment, the particles having a 50% average particle diameter of 2 to 10 μm.
The 50% average particle size may be measured herein using a particle size measuring apparatus based on a laser diffraction/scattering method. In the present invention, for example, it is preferable to measure the 50% average particle diameter using a particle size distribution measuring device (by a laser diffraction/scattering (scattering) method) LS230 (manufactured by Beckman Coulter, inc.) or a laser diffraction-type particle size distribution measuring device SALD-2001 system (manufactured by Shimadzu sessakusho ltd.) because the 50% average particle diameter can be measured in a simple and cost-effective manner and the general characteristics are high. In the present invention, the expression "50% average particle diameter" as used herein means a particle diameter of 50% of the total particles in terms of the cumulative value in the particle size distribution results of the dispersion measured using a particle size measuring apparatus based on a laser diffraction/scattering method. In particular, the 50% average particle size refers to the particle size at one point, where the total number of particles reaches 50%, when the number of particles is added in order of increasing particle size in the particle size distribution.
The 50% average particle size herein is also referred to as the average fat globule diameter in dairy products such as milk and dairy beverages, and the expression "50% average particle size" as used herein refers to the expression of average fat globule diameter.
In the whey protein aggregate used in the present invention, when many particles having a diameter of not more than 1 μm are contained, the swelling degree stability of the emulsion containing air bubbles which is actually obtained is low, so that the shape cannot be maintained to be retained.
For example, whey protein aggregates, including particles having an average particle size of 2 to 10 μm 50%, may be prepared by subjecting a whey protein solution to a heat treatment at 75 to 85 ℃ and a mechanical shearing treatment simultaneously for 5 to 10 minutes. For example, when a homomixer (t.k. Homo MIXERMARKII Model 2.5, manufactured by PRIMIX corporation) is used, the whey protein aggregate may be preferably prepared by simultaneously subjecting the whey protein solution to a heat treatment at 75 to 85 ℃ and a mechanical shearing treatment at a rotation speed of 100 to 10000rpm for 5 to 10 minutes.
In addition, in the preparation of the whey protein aggregate, the whey protein solution preferably has a pH of 4.0 to 6.0, more preferably a pH of 4.5 to 5.0, and still more preferably a pH of 4.6 to 4.7, at which the amount of the whey protein aggregate formed is the highest, the efficiency of encapsulating the carnitine is the best, and the carnitine sustained-release effect is the best.
The whey protein aggregate used in the present invention may be in the form of a liquid, or may be in the form of a liquid or gel obtained by concentration by a vacuum evaporation method or a freeze concentration method, or a powder obtained by drying by a spray drying method or a freeze drying method, and the shape and properties of the whey protein aggregate are not particularly limited. Preferably, however, it is a liquid form that does not dry whey protein aggregates and that comprises water derived from a whey protein solution.
In the present invention, "containing air bubbles" as used herein is not limited in theory, and the preparation containing air bubbles comprises water or oil as a dispersion medium and whey protein aggregate particles surrounding the air bubbles, instead of fat-derived fat particles. In the art to which the present invention pertains, formulations containing gas bubbles are sometimes referred to as foamable oil-in-water emulsions or foamable water-in-oil emulsions.
As used herein, a "low-fat or defatted" sustained release formulation has a fat content that has been reduced below conventional values or has been reduced infinitesimally to zero. In the low-fat or defatted formulation of the present invention, in particular, the fat content (concentration) varies depending on the type of sustained-release formulation. For example, in the case of a fat component comprising milk fat, the fat content of the low-fat sustained-release preparation may be 0.5 to 5wt%, preferably 0.5 to 3wt%, more preferably 0.5 to 1.5wt% of the sustained-release preparation, and in the case of a fat component comprising milk fat, the fat content of the fat-free sustained-release preparation may be 0.55wt% or less.
The sustained-release preparation of the present invention may optionally contain, in addition to whey protein aggregates, one or more of milk products or other dairy products, sugar, sweetened egg yolk, flavors, salts (e.g., common salt), any sugar commonly used in the field of microcrystalline foods, preferably, glucose, fructose, sugar, reduced maltose, granulated sugar, isomerized sugar, high fructose liquid sugar, gummy starch syrup, confectionery powder, high intensity sweetener (e.g., xylitol, stevia (stevia) extract, palatinose, aspartame K, stevia, saccharin sodium or sucralose), sugar alcohol (e.g., erythritol, xylitol, sorbitol, maltitol, lactitol, isomalt (parachinit), or isomalt.
The fat and oil used in the present invention are not particularly limited as long as the fat content (concentration) of the sustained-release preparation can be adjusted to a desired value. The fats and oils used in the present invention are preferably vegetable fats and vegetable oils.
Examples
Example 1
53g of L-carnitine (L-carnitine), 536g of whey protein concentrate (whey protein concentrate solid content: 97wt%, wherein skim milk solid content: 96wt%, fat content: 1wt%, total content of lactalbumin and lactoglobulin was about 66 wt%) obtained by adjusting protein content to 34wt% and spray-drying, and 1810g of water were put into a turbine mixer (manufactured by Scanima) to mix to obtain a mixture, and then the mixture was heated to 55 ℃, dissolved with stirring at 2500rpm, and subjected to mechanical shearing treatment to obtain a whey protein solution having a pH of 4.6. Continuously performing heating treatment and mechanical shearing treatment, and continuously performing mechanical shearing treatment at 85 deg.C for 25min when the temperature of whey protein solution reaches 85 deg.C to coagulate whey protein. Then, the heat treatment was stopped, and the cooling system was started while continuing the mechanical shearing treatment at 2500rpm until the temperature dropped below 40 ℃, and the mechanical shearing treatment was stopped to obtain a whey protein aggregate.
The whey protein aggregate granules thus obtained had a D50 of 3.5 μm, in which 62.6wt% of L-carnitine was encapsulated in the granules, and the balance L-carnitine was present in water.
Example 2
53g of L-carnitine (L-carnitine), 536g of a whey protein concentrate obtained by adjusting the protein content to 34wt% and performing spray drying (the solid content of the whey protein concentrate is 97% by weight, wherein the solid content of skim milk is 96% by weight, the fat content is 1% by weight, and the total content of lactalbumin and lactoglobulin is about 40%), and 1810g of water were mixed in a turbine mixer (manufactured by Scanima) to obtain a mixture, and then the mixture was heated to 55 ℃, dissolved with stirring at 2500rpm, and subjected to mechanical shearing treatment to obtain a whey protein solution having a pH of 4.7. Continuously performing heating treatment and mechanical shearing treatment, and continuously performing mechanical shearing treatment at 85 deg.C for 25min to coagulate whey protein when the temperature of whey protein solution reaches 85 deg.C. Then, the heat treatment was stopped, and the cooling system was started while continuing the mechanical shearing treatment at 2500rpm until the temperature dropped below 40 ℃, and the mechanical shearing treatment was stopped to obtain a whey protein aggregate.
The whey protein aggregate granules thus obtained had a D50 of 2.5 μm, wherein 42.3wt% of L-carnitine was encapsulated in the granules, and the balance L-carnitine was present in water.
Example 3
110g of L-carnitine (L-carnitine), 502g of whey protein concentrate (containing approximately 80% of lactalbumin and lactoglobulin), which was obtained by freeze-spray drying, and 1210g of water were mixed in a turbine mixer (manufactured by Scanima) to obtain a mixture, and then the mixture was heated to 55 ℃, dissolved with stirring at 2500rpm, and subjected to mechanical shearing treatment to obtain a whey protein solution having a pH of 4.8. Continuously performing heating treatment and mechanical shearing treatment, and continuously performing mechanical shearing treatment at 75 deg.C for 60min when the temperature of whey protein solution reaches 75 deg.C to coagulate whey protein. Then, the heat treatment was stopped, and the cooling system was started while continuing the mechanical shearing treatment at 2500rpm until the temperature dropped below 40 ℃, and the mechanical shearing treatment was stopped to obtain a whey protein aggregate.
The whey protein aggregate granules thus obtained had a D50 of 4.5 μm, wherein 74.5wt% of L-carnitine was encapsulated in the granules, and the balance L-carnitine was present in water.
Example 4
110g of L-carnitine (L-carnitine), 502g of the whey protein concentrate (containing approximately 40% of lactalbumin and lactoglobulin) obtained by freeze-spray drying, and 1210g of water were mixed in a turbine mixer (manufactured by Scanima) to obtain a mixture, and then the mixture was heated to 55 ℃, dissolved with stirring at 2500rpm, and subjected to mechanical shearing treatment to obtain a whey protein solution having a pH of 4.7. Continuously performing heating treatment and mechanical shearing treatment, and continuously performing mechanical shearing treatment at 75 deg.C for 60min when the temperature of whey protein solution reaches 75 deg.C to coagulate whey protein. Then, the heat treatment was stopped, and the cooling system was started while continuing the mechanical shearing treatment at 2500rpm until the temperature dropped below 40 ℃, and the mechanical shearing treatment was stopped to obtain a whey protein aggregate.
The whey protein aggregate granules thus obtained had a D50 of 3.5 μm, in which 41.7wt% of L-carnitine was encapsulated in the granules, and the balance L-carnitine was present in water.
Example 5
110g of L-carnitine (L-carnitine), 502g of a whey protein concentrate (in which the total content of lactalbumin and lactoglobulin is about 80%) obtained by freeze-spray drying, and 1210g of water were mixed in a turbine mixer (manufactured by Scanima) to obtain a mixture, and then the mixture was heated to 55 ℃, dissolved with stirring at 2500rpm, and subjected to mechanical shearing treatment to obtain a whey protein solution and the pH of the solution was adjusted to 6.2 with a NaOH solution. Continuously performing heating treatment and mechanical shearing treatment, and continuously performing mechanical shearing treatment at 75 deg.C for 60min to coagulate whey protein when the temperature of whey protein solution reaches 75 deg.C. Then, the heat treatment was stopped, and the cooling system was started while continuing the mechanical shearing treatment at 2500rpm until the temperature dropped below 40 ℃, and the mechanical shearing treatment was stopped to obtain a whey protein aggregate.
The whey protein aggregate granules thus obtained had a D50 of 3.8 μm, in which 32.2wt% of L-carnitine was encapsulated in the granules, the remainder being in water.
Example 6
110g of L-carnitine (L-carnitine), 502g of whey protein concentrate (containing approximately 80% of lactalbumin and lactoglobulin) obtained by freeze-spray drying, and 1210g of water were mixed in a turbine mixer (manufactured by Scanima) to obtain a mixture, and then the mixture was heated to 55 ℃, dissolved with stirring at 2500rpm, and subjected to mechanical shearing treatment to obtain a whey protein solution, the pH of which was adjusted to 3.7 (adjusted with HCl or acetic acid). Continuously performing heating treatment and mechanical shearing treatment, and continuously performing mechanical shearing treatment at 75 deg.C for 60min when the temperature of whey protein solution reaches 75 deg.C to coagulate whey protein. Then, the heat treatment was stopped, and the cooling system was started while continuing the mechanical shearing treatment at 2500rpm until the temperature dropped below 40 ℃, and the mechanical shearing treatment was stopped to obtain a whey protein aggregate.
The whey protein aggregate granules thus obtained had a D50 of 2.5 μm, in which 38.1wt% of L-carnitine was encapsulated in the granules, the remainder being in water.
Example 7
35g of L-carnitine (L-carnitine), 623g of a whey protein concentrate (containing approximately 50% of lactalbumin and lactoglobulin) obtained by freeze-spray drying, and 1310g of water were mixed in a turbine mixer (manufactured by Scanima) to obtain a mixture, and then the mixture was heated to 55 ℃, dissolved with stirring at 2500rpm, and subjected to mechanical shearing treatment to obtain a whey protein solution having a pH of 4.5. Continuously performing heating treatment and mechanical shearing treatment, and continuously performing mechanical shearing treatment at 75 deg.C for 45min when the temperature of whey protein solution reaches 75 deg.C to coagulate whey protein. Then, the heat treatment was stopped, and the mechanical shearing treatment was continued at 2500rpm while the cooling system was turned on until the temperature was lowered to 40 ℃ or lower, and the mechanical shearing treatment was stopped to obtain a whey protein aggregate.
The whey protein aggregate granules thus obtained had a D50 of 6.3 μm, wherein 51.5wt% of L-carnitine was encapsulated in the granules, and the balance L-carnitine was present in water.
Example 8
35g of L-carnitine (L-carnitine), 623g of a whey protein concentrate (containing approximately 50% of lactalbumin and lactoglobulin) obtained by freeze-spray drying, and 1310g of water were mixed in a turbine mixer (manufactured by Scanima) to obtain a mixture, and then the mixture was heated to 55 ℃, dissolved with stirring at 2500rpm, and subjected to mechanical shearing treatment to obtain a whey protein solution having a pH of 4.5. Continuously performing heating treatment and mechanical shearing treatment, and continuously performing mechanical shearing treatment at 75 deg.C for 20min to coagulate whey protein when the temperature of whey protein solution reaches 75 deg.C. Then, the heat treatment was stopped, and the cooling system was started while continuing the mechanical shearing treatment at 2500rpm until the temperature dropped below 40 ℃, and the mechanical shearing treatment was stopped to obtain a whey protein aggregate.
The whey protein aggregate granules thus obtained had a D50 of 4.6 μm, in which 35.5wt% of L-carnitine was encapsulated in the granules, the remainder being in water.
Example 9
55g of L-carnitine (L-carnitine), 475g of the whey protein concentrate obtained by freeze-spray drying, in which the total content of lactalbumin and lactoglobulin was about 50%, and 2500g of water were mixed in a turbine mixer (manufactured by Scanima) to obtain a mixture, and then the mixture was heated to 55 ℃, dissolved with stirring at 2500rpm, and subjected to mechanical shearing treatment to obtain a whey protein solution having a pH of 4.4. Continuously performing heating treatment and mechanical shearing treatment, and continuously performing mechanical shearing treatment at 65 deg.C for 60min to coagulate whey protein when the temperature of whey protein solution reaches 65 deg.C. Then, the heat treatment was stopped, and the cooling system was started while continuing the mechanical shearing treatment at 2500rpm until the temperature dropped below 40 ℃, and the mechanical shearing treatment was stopped to obtain a whey protein aggregate.
The D50 of the whey protein aggregate granules thus obtained was 6.8 μm, in which 58.7wt% of L-carnitine was encapsulated in the granules, the remainder being in water.
Example 10
55g of L-carnitine (L-carnitine), 475g of a whey protein concentrate obtained by freeze spray drying, in which the total content of lactalbumin and lactoglobulin was about 50%, and 2500g of water were put into a turbine mixer (manufactured by Scanima) to mix and obtain a mixture, and then the mixture was heated to 55 ℃, dissolved with stirring at 2500rpm, and subjected to mechanical shearing treatment to obtain a whey protein solution having a pH of 4.4. Continuously performing heating treatment and mechanical shearing treatment, and continuously performing mechanical shearing treatment at 45 deg.C for 60min to coagulate whey protein when the temperature of whey protein solution reaches 45 deg.C. Then, the heat treatment was stopped, and the cooling system was started while continuing the mechanical shearing treatment at 2500rpm until the temperature dropped below 40 ℃, and the mechanical shearing treatment was stopped to obtain a whey protein aggregate.
The whey protein aggregate granules thus obtained had a D50 of 3.4 μm, wherein 31.2wt% of L-carnitine was encapsulated in the granules, and the balance L-carnitine was present in water.
Comparative example 1
The method was performed in accordance with example 1, except that L-carnitine was not added during the preparation of the protein aggregate, and a sample having a particle size in accordance with the whey protein aggregate particle of example 1 was selected and physically mixed with L-carnitine to obtain a whey protein aggregate particle without L-carnitine coated therein.
Comparative example 2
The method was performed in accordance with example 3, except that the preparation of the protein aggregate was performed without adding L-carnitine, and the sample having a particle size in accordance with the whey protein aggregate particle of example 3 was physically and uniformly mixed with L-carnitine, thereby obtaining a whey protein aggregate particle without L-carnitine coated therein.
Comparative example 3
The same procedure as in example 7, except that L-carnitine was not added in the preparation of the protein aggregate, and a sample having a particle size identical to that of the whey protein aggregate granules of example 7 was selected and physically mixed with L-carnitine to obtain whey protein aggregate granules without coating L-carnitine therein.
Comparative example 4
The same as in example 9, except that no L-carnitine was added during the preparation of the protein aggregate, and the sample having the same particle size as the whey protein aggregate granules of example 9 was physically and uniformly mixed with L-carnitine, to obtain whey protein aggregate granules without coating L-carnitine therein.
In vivo absorption test
After oral administration of samples of the beagle dogs in the examples and the control examples, wherein the content of L-carnitine (L-carnitine) is the same, blood is collected at different times, serum is separated, the blood concentration of the L-carnitine (L-carnitine) is determined, a blood concentration-time curve is drawn, and the area AUC of the blood concentration and the time at different times t is calculated 0→t (corresponding to cumulative blood drug level) and the blood drug concentration over time and the area AUC over time 0→∞ (corresponding to the total cumulative blood content) of the blood. The results are shown in Table 1.
TABLE 1-1 results of carnitine absorption test in vivo for samples of examples and comparative examples
| 0h(％) | 2h(％) | 4h(％) | 6h(％) | 8h(％) | 10h(％) | |
| Example 1 | 0 | 43.7 | 68.8 | 83.7 | 96.6 | 100 |
| Example 2 | 0 | 58.7 | 82.7 | 95.7 | 100 | |
| Comparative example 1 | 0 | 72.2 | 92.2 | 100 |
TABLE 1-2 test results of carnitine absorption in vivo for samples of examples and comparative examples
| 0h(％) | 2h(％) | 4h(％) | 6h(％) | 8h(％) | 10h(％) | |
| Example 3 | 0 | 34.5 | 49.6 | 67.3 | 87.9 | 96.5 |
| Example 4 | 0 | 57.5 | 78.9 | 86.5 | 97.3 | 100 |
| Example 5 | 0 | 67.1 | 88.5 | 97.7 | 100 | |
| Example 6 | 0 | 62.7 | 81.8 | 91.7 | 100 | |
| Comparative example 2 | 0 | 75.5 | 94.8 | 100 |
TABLE 1-3 test results of carnitine absorption in vivo in samples of examples and control examples
TABLE 1-4 results of carnitine absorption test in vivo for samples of examples and comparative examples
| 0h(％) | 2h(％) | 4h(％) | 6h(％) | 8h(％) | 10h(％) | |
| Example 9 | 0 | 48.9 | 72.6 | 88.3 | 98.7 | 100 |
| Example 10 | 0 | 68.7 | 87.7 | 98.2 | 100 | |
| Comparative example 4 | 0 | 72.2 | 92.2 | 100 |
While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (1)
1. A carnitine sustained-release preparation, which is characterized by comprising L-carnitine and whey protein aggregates in a mass ratio of: 0.5-10wt%, wherein the content of the whey protein aggregate is 6-30wt%, the whey protein aggregate is particles with the average particle size of 50% being 2-10 mu m, and at least 50wt% of L-carnitine is dispersed in the whey protein aggregate particles;
the preparation process of the carnitine sustained-release preparation comprises the following steps: adding L-carnitine and whey protein into water, uniformly mixing to obtain a mixture, heating the mixture to 55 ℃, stirring and dissolving at a rotating speed of 2500rpm, and carrying out mechanical shearing treatment to obtain a whey protein solution, and continuing carrying out thermal treatment and mechanical shearing treatment, wherein when the temperature of the whey protein solution reaches 65-85 ℃, the mechanical shearing treatment is continuously carried out at the temperature of 65-85 ℃ for 25-60min, so that the solution contains whey protein aggregate particles with the D50 of 2-10 mu m, and the carnitine sustained-release preparation is obtained;
the total content of lactalbumin and lactoglobulin in the whey protein is not less than 50wt%;
the pH value of the whey protein solution is 4.5 to 5.0;
the sustained release formulation is low or fat free.
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