US-12616227-B2 - Stable carotenoid microcapsule having high bioavailability and preparation method therefor

US12616227B2US 12616227 B2US12616227 B2US 12616227B2US-12616227-B2

Abstract

A stable carotenoid microcapsule having high bioavailability and a preparation method therefor. The method includes the following steps: a) mixing carotenoid crystals with an organic solvent, and dissolving the mixture to obtain a carotenoid solution; b) introducing the carotenoid solution and a grease into a dispersion system to fully disperse carotenoid into the grease, and vaporizing the organic solvent to obtain a carotenoid-containing dispersion liquid; c) mixing the carotenoid-containing dispersion liquid and a protective colloid aqueous solution, and emulsifying the mixture to obtain an emulsion; and d) performing spray granulation and drying to obtain a carotenoid microcapsule.

Inventors

Jiandong Li
Xiang Liu
Lidan Qi
Zhirong Chen
Lifang Shi
Guodong HUANG
Lishuang Pan
Hong Yin
Dan Qiu
QILEI ZHANG
Xiaoyong Zhu

Assignees

ZHEJIANG NHU COMPANY LTD.
ZHEJIANG UNIVERSITY
XINCHANG NHU VITAMINS COMPANY LTD.

Dates

Publication Date: 20260505
Application Date: 20210429
Priority Date: 20200731

Claims (17)

1 . A method for preparing a carotenoid microcapsule comprising: a) mixing carotenoid crystals with an organic solvent, and dissolving the carotenoid crystals in the organic solvent to obtain a carotenoid solution; b) introducing the carotenoid solution and a hot grease into a dispersion system to fully disperse the carotenoid into the hot grease, and vaporizing the organic solvent to obtain a carotenoid-containing dispersion liquid; c) mixing the carotenoid-containing dispersion liquid with an aqueous solution of a protective colloid to obtain a mixture, and emulsifying the mixture to obtain an emulsion; and d) spraying and granulating the emulsion, and drying to obtain the carotenoid microcapsule, wherein the dispersion system in step b) comprises a dispersing device, a container connected to the dispersing device, a conveying device, and a heating device, the dispersing device is configured for mixing the carotenoid solution obtained in step a) with the hot grease or a circulating material to fully disperse the carotenoid into the hot grease; the conveying device is configured for conveying substances in the dispersion system; and the heating device is configured for heating a grease or the circulating material to obtain a liquid hot grease or a liquid circulating material, the dispersing device comprises a contact portion, a constriction portion, and an expansion portion connected and communicated with each other in sequence, the contact portion is provided with a spray port and an atomization port, the spray port is configured to introduce the liquid hot grease or the liquid circulating material into the contact portion; the atomization port is configured to transform the carotenoid solution obtained in step a) into tiny carotenoid droplets, so that the carotenoid droplets are capable of being mixed with the liquid hot grease or the liquid circulating material in the contact portion, an organic solvent in the carotenoid droplets is capable of being vaporized, thereby forming carotenoid particles which are dispersed in the hot grease; and the constriction portion is configured to mix the carotenoid droplets formed in the contact portion with the liquid hot grease and make the organic solvent in the carotenoid droplets vaporized, such that a resulting material is introduced into the expansion portion, and then introduced into the container communicated with the dispersing device.
2 . The method of claim 1 , wherein the container connected with the dispersing device further comprises a vacuum port configured for discharging the vaporized organic solvent from the container.
3 . The method of claim 1 , wherein the dispersion system is a continuous operation system or a batch operation system.
4 . The method of claim 1 , wherein a residence time of the substances in the dispersion system is less than or equal to 20 hours.
5 . The method of claim 1 , wherein a temperature of the hot grease is in a range of 60 degrees centigrade to 100 degrees centigrade.
6 . The method of claim 1 , wherein in step b), vaporizing and removing a part of the organic solvent in the carotenoid solution, wherein a content of a first residual organic solvent in the carotenoid-containing dispersion liquid is less than 1%.
7 . The method of claim 1 , wherein step c) further comprises a step of removing a second residual organic solvent in the emulsion after emulsifying the mixture.
8 . The method of claim 1 , wherein in step b), the carotenoid-containing dispersion liquid comprises the carotenoid particles and dissolved carotenoids, and wherein an average particle size of the carotenoid particles in the carotenoid-containing dispersion liquid is in a range of 0.05 μm to 0.2 μm.
9 . The method of claim 1 , wherein in step b), a mass ratio of the hot grease and the carotenoid crystals is in a range of 0.7:1 to 20:1.
10 . The method of claim 1 , wherein in step c), the emulsifying the mixture is processed by a method which is one or more selected from a group consisting of a high pressure homogeneous emulsification, an in-line pipeline high shear emulsification, a supergravity emulsification, a static mixing, and any combination thereof.
11 . The method of claim 1 , wherein the protective colloid is starch octenyl succinate.
12 . The method of claim 1 , wherein after the emulsifying the mixture in step c), the carotenoid-containing dispersion liquid is dispersed in the protective colloid to form a dispersed phase, an average particle size of the dispersed phase is in a range of less than 0.7 μm, the dispersed phase comprises at least one kind of carotenoid particle and at least one kind of grease, and the carotenoid particle is nanometer-sized, dispersed in and encapsulated by the grease.
13 . The method of claim 1 , wherein the organic solvent of step a) is dichloromethane.
14 . The method of claim 1 , wherein a mass ratio of the organic solvent to the carotenoid crystals in step a) is in a range of 100:1 to 2000:1.
15 . The method of claim 1 , wherein in step a), further adding antioxidants to the carotenoid solution, wherein the antioxidant is tocopherol; and/or a mass ratio of the antioxidants to the carotenoid crystals is in a range of 0.1:1 to 3:1.
16 . The method of claim 1 , wherein the hot grease in step b) is physiologically acceptable grease, and the physiologically acceptable grease is selected from one or more selected from a group consisting of wax, vegetable oil, and hydrogenated vegetable oil, wherein the wax is beeswax; and/or the vegetable oil is soybean oil; and/or the hydrogenated vegetable oil is hydrogenated palm oil.
17 . The method of claim 1 , wherein the carotenoid crystals of step a) is astaxanthin.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS The present disclosure is a National Stage application of International Application No. PCT/CN2021/090793 filed on Apr. 29, 2021, which claims all benefits accruing from China Patent Application No. 202010756509.4, filed on Jul. 31, 2020, in the China National Intellectual Property Administration, and titled “STABLE CAROTENOID MICROCAPSULE HAVING HIGH BIOAVAILABILITY AND PREPARATION METHOD THEREFOR”, both of which are hereby incorporated by reference. TECHNICAL FIELD The present disclosure relates to a field of pharmaceutical and chemical industry, in particular to a stable carotenoid microcapsule having high bioavailability and a method for preparing the same. BACKGROUND Carotenoids are a class of polyene compounds having a plurality of unsaturated bonds. As one of the most important natural pigments, carotenoids have a wide range of biological activities, including various effects such as pro-vitamin A activity, antioxidant function, anti-tumor function, eye protection, cardiovascular disease prevention, osteoporosis prevention, weight loss promotion and skin protection, etc. Therefore, carotenoids have attracted more and more attention from researchers in the fields of medicine, food, fodder, aquaculture, cosmetics, and the like. Since most carotenoids are insoluble in water and rarely soluble in vegetable oils, and they are highly unstable due to chemical substances, machinery action, light, oxygen, and heat, etc., during food processing and storage, limiting their applications in functional foods. In addition, as micronutrients, physiological efficacy of carotenoids mainly depends on their bioavailability in a body. A large number of studies have shown that a state and a particle size of carotenoids have a great influence on their bioavailability. Specifically, the smaller the particle size of carotenoid particles are, the easier they can be absorbed and utilized after being ingested by an organism, that is, the higher the bioavailability they have. Thus, people always try to reduce the particle size of carotenoids, so that the particle size of carotenoids can be micron-sized or even nanoscale. Accordingly, current developments and researches of carotenoids focus on selecting a dosage form with fine particles, good stability and high bioavailability as an intake carrier of carotenoids. At present, a variety of health foods and dietary supplements containing one or multiple carotenoids on the market, such as tablets, hard capsules, soft capsules, and oil suspensions of carotenoids, microcapsules of carotenoids, nano emulsions of carotenoids, and liposomes of carotenoids, which can be filled in the soft capsules. However, surfactants added in preparation processes of the soft capsules, the nano emulsions and the liposomes may cause side effects and lead to anaphylactic reactions in human body. In addition, the soft capsules, the nano emulsions and the liposomes are prone to delamination, oxidation and deterioration, etc., limiting their applications. According to molecular nutrition, in order to realize the bioavailability of carotenoids, it is necessary to avoid their destruction and degradation in a digestive tract to the greatest extent, such that the carotenoids can successfully reach an intestinal tract, and form micromicelles together with free fatty acids, monoglycerides and bile salts. As such, the carotenoids may be absorbed by small intestinal mucosal cells, and brought into various organs in the body by a lymphatic circulatory system to exert its health care effect. In view of the defects of the conventional art and characteristics of digestion and absorption of carotenoids in the body, the present disclosure intends to find an efficient and simple method, by which an organic solvent can be quickly removed from a product, so as to obtain carotenoid preparations having small particle sizes, good embedding effect, high stability and high bioavailability. SUMMARY In the literature, methods for preparing carotenoid preparations in various dosage forms have been reported. In Chinese patent No. CN101828693A, a carotenoid oil suspension with a particle size of about 10 μm was obtained by processing carotenoid crude crystals with tetrahydrofuran, ethanol and vegetable oil, etc. In Chinese patent No. CN102552173B, a carotenoid oil suspension with an average particle size of less than 5 μm was obtained by a process of introducing a carotenoid solution into vegetable oil by methods of atomization. However, uniformity and particle sizes of the carotenoids obtained in both of the above processes cannot reach an emulsion level. In addition, carotenoids have poor chemical stability in oil solution, and are prone to side reactions. Moreover, it is not convenient enough to apply oil suspension preparations in fodder, food and health care products industries. In Chinese patent No. CN108030063A, β-carotene, monoglyceride, triglyceride and vitamin E were used as an oil phas