CN112438950A

CN112438950A - Beta-carotene transparent water dispersion and preparation method thereof

Info

Publication number: CN112438950A
Application number: CN201910758647.3A
Authority: CN
Inventors: 乐园; 靳俊升; 王传琦; 卫宏靓; 吕希坤; 曾晓飞
Original assignee: Ningbo Haiqi Hesheng Huanneng Technology Co ltd; Beijing University of Chemical Technology
Current assignee: Ningbo Haiqi Hesheng Huanneng Technology Co ltd; Beijing University of Chemical Technology
Priority date: 2019-08-16
Filing date: 2019-08-16
Publication date: 2021-03-05

Abstract

The invention discloses a transparent beta-carotene water dispersion, which comprises the following components in percentage by mass: beta-carotene 0.01-5%; 0.5 to 15 percent of emulsifier; 0.5-15% of optionally present coemulsifiers; 0.01 to 0.2 percent of antioxidant; the balance of water. The aqueous dispersion has good stability, wherein the particle size of beta-carotene is less than 100nm, and the beta-carotene has good water solubility and high bioavailability. The invention also discloses a preparation method of the transparent aqueous dispersion.

Description

Beta-carotene transparent water dispersion and preparation method thereof

Technical Field

The invention relates to the field of biotechnology. More particularly, relates to a transparent water dispersion of beta-carotene and a preparation method thereof.

Background

The beta-carotene can maintain the health level of human bodies, prevent human chronic diseases and promote the growth and development of infants, and is a natural functional component with multiple physiological activities. However, beta-carotene contains a plurality of unsaturated bonds, so that the beta-carotene has poor chemical stability, is easy to decompose and lose efficacy when meeting light and oxygen, is used as a fat-soluble vitamin, and is not soluble in water and difficult to digest and absorb by human bodies. Therefore, a stable and efficient delivery system is designed, and plays a crucial role in improving the content, stability and bioavailability of the beta-carotene.

Nanoemulsions are dispersions of two immiscible liquids stabilized with suitable surfactants, having high optical clarity, physical stability and easy digestibility, and are effective delivery systems for absorbing, protecting and releasing various functional food ingredients. Smaller particle size not only results in long term physical stability of the nanoemulsion, but also improves the bioavailability of beta-carotene. From the viewpoint of improving oral bioavailability and reducing production costs, oil-in-water (O/W) nanoemulsions are one of excellent delivery methods of β -carotene.

According to different input energies, the preparation method of the nano emulsion is divided into a low-energy emulsification method and a high-energy emulsification method, wherein the low-energy emulsification method comprises a phase transition temperature method, a phase inversion method, a membrane emulsification method, a self-emulsification method and the like. The high-energy emulsification method includes a shear stirring method, a high-pressure homogenization method, an ultrasonic emulsification method and the like. In the prior art, the nano emulsion is prepared on the basis of a low-energy emulsification method technology, but a large amount of surfactant is needed to realize smaller particle size and emulsion stability; the high-energy emulsification method can effectively reduce and control the particle size, but the shearing stirring method and the ultrasonic method are difficult to realize industrial amplification, and can only realize small-batch production, and the high-pressure homogenization method which is applied more in industry can cause physical damage to the property of the medicine because of the high pressure required in the preparation process, and can not be used in all systems. The existing preparation method mainly adopts a two-step method, namely stirring the water phase and the mixed solution at a certain temperature to obtain a coarse emulsion, and then carrying out secondary processing by a high-pressure homogenizer or other mechanical equipment to obtain the nano-emulsion with small particle size and narrow distribution.

The current patents on beta-carotene nanoemulsions mostly adopt beta-carotene dissolved in solvent oil as an oil phase, such as medium-chain fatty glyceride (CN 108041598A) or vegetable oil (CN 108041594 a, CN 108835490 a). However, the solubility of the common solvent oil to the beta-carotene is low, so that the content of the beta-carotene in the nano emulsion is limited. The invention directly uses the beta-carotene fusion as the oil phase, solves the problem of low content of the beta-carotene and improves the content of the beta-carotene in the water dispersion.

Patent CN 104470373A proposes a beta-carotene-containing oil-in-water and a preparation method thereof, which adopts pre-emulsification and then high-pressure homogenization to prepare nano emulsion with the particle size of 50-400nm, but the preparation needs two steps, and the high pressure in the homogenization process can cause physical damage to the property of the medicine, thereby being difficult to realize industrial amplification and only being capable of producing in small batch.

CN 109105723A proposes a beta-carotene emulsion and its preparation method, which adopts vegetable oil to dissolve beta-carotene, the emulsification process is firstly stirred for 2-3min, then cut for 2-5min, homogenized for 1-3 times under 3-40Mpa, and the emulsion can be obtained after sterilization. Is an intermittent production process and is not easy to realize continuous production.

Disclosure of Invention

In view of the above problems, a first object of the present invention is to provide a transparent aqueous dispersion of β -carotene, which has a particle size of less than 100nm, good water solubility, high bioavailability, and good stability.

The second purpose of the invention is to provide a preparation method of the beta-carotene transparent aqueous dispersion, the particle size of the beta-carotene in the aqueous dispersion prepared by the method is less than 100nm, the dispersion has good stability, the problems of poor water solubility and low bioavailability of the beta-carotene are solved, the preparation process is simple, continuous production can be realized, no amplification effect exists, and the method is easy to industrialize.

In order to achieve the first purpose, the invention adopts the following technical scheme:

the transparent beta-carotene water dispersion comprises the following raw materials in percentage by mass:

optionally, the raw materials comprise the following components in percentage by mass:

in the present invention, "optionally present" means that it may or may not be present, i.e. that the starting material comprises or does not comprise a co-emulsifier.

Optionally, the emulsifier is selected from one or more of tween 20, tween 80, span 80, polyoxyethylene hydrogenated castor oil, castor oil polyoxyethylene ether, poloxamer, fatty acid monoglyceride, soybean phospholipid, and egg yolk lecithin.

Optionally, the co-emulsifier is selected from one or more of absolute ethyl alcohol, 1,2 propylene glycol, glycerol, n-butanol, polyethylene glycol 400.

The emulsifier and the co-emulsifier have strong matching capability with the beta-carotene, and form an emulsion system with small particle size, wide application range and strong stability.

Optionally, the antioxidant is selected from one or more of vitamin E, antioxidant quinoline, butyl hydroxy anisole, 2, 6-di-tert-butyl-4-methylphenol and tert-butyl hydroquinone. The addition mass is preferably 0.06 to 0.1%.

Optionally, the mass ratio of the emulsifier to the co-emulsifier is 1:5 to 5: 1.

Optionally, the mass ratio of the emulsifier to the co-emulsifier is 1:4 to 4: 1.

Optionally, the mass ratio of the emulsifier to the co-emulsifier is 1:3 to 3: 1.

Optionally, the mass ratio of the emulsifier to the co-emulsifier is 1:2 to 2: 1.

The mass ratio of the emulsifier to the co-emulsifier also affects the stability and particle size distribution of the resulting aqueous dispersion, and when the ratio of the emulsifier to the co-emulsifier is in the range defined in the above example and the ratio range is smaller, the stability of the resulting aqueous dispersion is better, and the β -carotene can be controlled to be 100nm or less.

Optionally, the weight ratio of beta-carotene to the sum of emulsifier and co-emulsifier is from 1:15 to 1: 0.5. Further optionally, the weight ratio of beta-carotene to the sum of emulsifier and co-emulsifier includes, but is not limited to, 1:15-1:1, 1:15-1:3, 1:15-1:5, 1:15-1:10, 1:10-1:0.5, 1:10-1:1, 1:10-1:3, 1:10-1:5, 1:5-1:0.5, 1:5-1:3, 1:3-1:0.5, 1:8-1:1, 1:3-1:1, 1:5-1:1, and the like. The emulsifying capacity is strong within the range, the integral stability of the water dispersion can be better ensured, and the use amount of the emulsifier and the co-emulsifier is small, and the toxic and side damage can be reduced to the maximum extent.

In order to achieve the second purpose, the invention adopts the following technical scheme:

the process for the preparation of a transparent aqueous dispersion of beta-carotene according to the first object above, comprising the steps of:

melting and mixing beta-carotene, an emulsifier, an optional auxiliary emulsifier and an optional antioxidant to obtain a mixed solution;

and mixing the mixed solution with water in an emulsifier to obtain the transparent beta-carotene water dispersion.

Optionally, the temperature of the melting is from 180 ℃ to 200 ℃.

Optionally, the emulsifier is one or more of a super-gravity rotating bed, an ultrasonic instrument, a microchannel reactor, and a water bath with magnetic stirring.

Optionally, the feed volume ratio of the mixed solution and water is from 1:10 to 1: 150. Specifically, exemplary feed volume ratios of mixed solution and water include, but are not limited to, 1:10-1:120, 1:10-1:100, 1:10-1:80, 1:10-1:60, 1:20-1:150, 1:20-1:120, 1:20-1:100, 1:20-1:80, 1:20-1:60, and the like.

Optionally, the mixed solution is added to the emulsifier at a rate of 1-30 ml/min. Specifically, exemplary rates of addition of the mixed solution to the emulsifier include, but are not limited to, 1-25ml/min, 1-20ml/min, 1-15ml/min, 1-10ml/min, 1-5ml/min, 5-30ml/min, 5-25ml/min, 5-20ml/min, 5-15ml/min, 5-10ml/min, 10-30ml/min, 10-25ml/min, 10-20ml/min, 10-15ml/min, and the like.

Optionally, the water is added to the emulsifier at a rate of 10-600 ml/min. Specifically, exemplary rates of addition of water to the emulsifier include, but are not limited to, 10-550ml/min, 10-500ml/min, 10-450ml/min, 10-400ml/min, 10-350ml/min, 10-300ml/min, 10-250ml/min, 10-200ml/min, 10-150ml/min, 10-100ml/min, 10-50ml/min, 50-600ml/min, 50-550ml/min, 50-500ml/min, 50-450ml/min, 50-400ml/min, 50-350ml/min, 50-300ml/min, 50-250ml/min, 50-200ml/min, 50-150ml/min, 50-100ml/min, water, 600ml/min for 100-.

Under the adding speed range of the mixed solution and water into the emulsifier, the particle size of the nano emulsion is smaller and the distribution is more uniform, and the obtained water dispersion liquid has clear appearance.

Optionally, the rotation speed of the emulsifier is 500-. Specifically, the method includes, but is not limited to, 500-2500r/min, 500-2000r/min, 500-1500r/min, 500-1000r/min, 1000-2800r/min, 1000-2500r/min, 1000-2000r/min, 1000-1500r/min, 1500-2800r/min, 1500-2500r/min, 1500-2000r/min, 2000-2800r/min, 2000-2500r/min, 1500-2500r/min, etc.

Optionally, the temperature at which the mixed solution and water are mixed in the emulsifier is from 25 ℃ to 85 ℃. Specifically, but not limited to, 25-75 ℃, 25-65 ℃, 25-55 ℃, 25-45 ℃, 25-35 ℃, 25-30 ℃, 30-85 ℃, 30-75 ℃, 30-65 ℃, 30-55 ℃, 30-45 ℃, 30-35 ℃, 35-85 ℃, 35-75 ℃, 35-65 ℃, 35-55 ℃, 35-45 ℃, 40-85 ℃, 40-75 ℃, 40-65 ℃, 40-55 ℃, 40-45 ℃, 45-85 ℃, 45-75 ℃, 45-65 ℃, 45-55 ℃, 50-85 ℃, 50-75 ℃, 50-65 ℃, 50-55 ℃, 30-60 ℃ and the like.

In the technical scheme of the invention, the selection of the surfactant and the cosurfactant, the selection of the weight ratio range of the surfactant and the cosurfactant, the selection of the feeding volume ratio range of the mixed solution and the water, the use of the emulsifier, the selection of the rotating speed range of the emulsifier and the selection of the mixing temperature are preferably adopted, and the conditions are matched with each other, so that the finally obtained nano emulsion in the water dispersion has smaller particle size, clear and transparent appearance and better stability.

Any range recited herein is intended to include the endpoints and any number between the endpoints and any subrange subsumed therein or defined therein.

The starting materials of the present invention are commercially available, unless otherwise specified, and the equipment used in the present invention may be any equipment conventionally used in the art or may be any equipment known in the art.

The invention has the following beneficial effects:

the transparent water dispersion liquid of beta-carotene provided by the invention does not contain the conventionally used oil, and the raw material composition and the proportion of the transparent water dispersion liquid of beta-carotene are limited, so that the problem of low solubility of the commonly used oil to the beta-carotene is solved, the limitation of the oil dosage to the content of the beta-carotene is overcome, the content of the beta-carotene in the water dispersion liquid is improved, and meanwhile, the water dispersion liquid has good stability. In the preparation method of the beta-carotene transparent aqueous dispersion provided by the invention, the beta-carotene is directly melted to be used as an oil phase, and the oil phase, the melted mixed solution of the emulsifier, the co-emulsifier and the antioxidant and water are emulsified and mixed to obtain the beta-carotene transparent aqueous dispersion with the grain size of less than 100nm, high content, high transparency and good stability; the preparation method improves the problem of poor water solubility of the beta-carotene, improves the bioavailability and stability of the beta-carotene, has simple process, easy realization, less energy consumption, high efficiency, low cost and easy amplification, and achieves the aim of industrial production.

Drawings

The following describes embodiments of the present invention in further detail with reference to the accompanying drawings.

FIG. 1 shows the particle size distribution of an aqueous dispersion of beta-carotene prepared in example 1 of the present invention.

FIG. 2 shows the particle size distribution of the aqueous dispersion of beta-carotene prepared in example 2 of the present invention.

FIG. 3 shows the results of the content stability of the transparent aqueous dispersions of beta-carotene obtained in the examples of the present invention and the comparative examples, when they were left at 4 ℃ for 30 days.

FIG. 4 shows the results of the content stability of the transparent aqueous dispersions of beta-carotene obtained in the examples of the present invention and the comparative examples after 30 days at room temperature.

FIG. 5 shows the results of the particle size stability of the transparent aqueous dispersions of beta-carotene obtained in the examples of the present invention and comparative examples after being left at 4 ℃ for 30 days.

FIG. 6 shows the results of particle size stability of transparent aqueous dispersions of beta-carotene obtained in examples of the present invention and comparative examples after standing at room temperature for 30 days.

Fig. 7 shows the morphology of the aqueous beta-carotene dispersions obtained in examples 1 and 2 and comparative examples 1 and 2 after being left at room temperature for 30 days.

Detailed Description

In order to more clearly illustrate the invention, the invention is further described below with reference to preferred embodiments and the accompanying drawings. Similar parts in the figures are denoted by the same reference numerals. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and is not to be taken as limiting the scope of the invention.

Example 1:

a process for preparing a transparent aqueous dispersion of beta-carotene comprising the steps of:

weighing 5g of beta-carotene, 35g of polyoxyethylene hydrogenated castor oil, 20g of 1, 2-propylene glycol and 1.2g of vitamin E, heating to 190 ℃ for melting, and uniformly mixing to obtain a mixed solution. The rotating speed of the super-gravity rotating bed is 2000rpm, the mixed oil phase is fed at 15ml/min, the pre-preheated purified water is fed at 300ml/min, the temperature of the system is controlled at 50 ℃, after the mixed solution is fed, the super-gravity rotating bed is closed, the transparent water dispersion liquid of the beta-carotene is obtained, and the content of the beta-carotene in the prepared transparent water dispersion liquid is 0.8%.

The nano emulsion prepared by the embodiment has clear and transparent appearance and the average particle size of about 20 nm.

Comparative example 1:

weighing 5g of beta-carotene, 2g of polyoxyethylene hydrogenated castor oil, 0.3g of 1, 2-propylene glycol and 1.2g of vitamin E, heating to 190 ℃ for melting, and uniformly mixing to obtain a mixed solution. The rotating speed of the super-gravity rotating bed is 2000rpm, the mixed oil phase is fed at 15ml/min, the pre-preheated purified water is fed at 300ml/min, the temperature of the system is controlled at 50 ℃, and after the mixed solution is fed, the super-gravity rotating bed is closed, so that the beta-carotene water dispersion is obtained. The content of beta-carotene in the prepared transparent aqueous dispersion was 0.1%.

The nano emulsion prepared by the comparative example can not keep clear and transparent appearance, and the average particle size is about 130 nm.

Example 2:

weighing 6g of beta-carotene, 35g of Tween 80, 20g of glycerol and 5g of antioxidant quinoline, heating to 190 ℃, melting and uniformly mixing to obtain a mixed solution. The rotating speed of the super-gravity rotating bed is 1500pm, the mixed oil phase is fed at 5ml/min, the pre-preheated purified water is fed at 500ml/min, the temperature of the system is controlled at 50 ℃, after the mixed solution is fed, the super-gravity rotating bed is closed, the beta-carotene water dispersion is obtained, and the content of the beta-carotene in the prepared transparent water dispersion is 0.2%.

The nano emulsion prepared by the embodiment has clear and transparent appearance and the average particle size of about 60 nm.

Comparative example 2:

weighing 6g of beta-carotene, 35g of Tween 80, 20g of 1, 2-propylene glycol and 5g of antioxidant quinoline, heating to 190 ℃, melting and uniformly mixing to obtain a mixed solution. The rotating speed of the super-gravity rotating bed is 1500rpm, the mixed oil phase is fed at 5ml/min, the pre-preheated purified water is fed at 500ml/min, the temperature of the system is controlled at 90 ℃, and after the mixed solution is fed, the super-gravity rotating bed is closed, so that the beta-carotene water dispersion is obtained. The content of beta-carotene in the prepared transparent aqueous dispersion was 0.2%.

The nano emulsion prepared by the comparative example can not keep clear and transparent appearance, and the average particle size is about 180 nm.

Example 3:

weighing 5g of beta-carotene, 25g of Tween 20, 15g of glycerol and 0.5g of butylated hydroxyanisole, heating to 190 ℃ for melting, and uniformly mixing by vortex oscillation to obtain a mixed solution. Introducing purified water preheated in advance into a sleeve type annular micro-channel reactor at a feeding speed of 300ml/min by using the mixed oil phase, controlling the temperature of the system to be 40 ℃, and obtaining a beta-carotene water dispersion after the mixed solution is fed, wherein the content of beta-carotene in the prepared transparent water dispersion is 2%.

The nano emulsion prepared by the embodiment has clear and transparent appearance and the average particle size of about 38 nm.

Example 4:

weighing 2g of beta-carotene, 6g of polyoxyethylene hydrogenated castor oil, 2g of 1, 2-propylene glycol and 0.1g of 2, 6-di-tert-butyl-4-methylphenol, heating to 190 ℃ for melting, and uniformly mixing by vortex oscillation to obtain a mixed solution. And (2) under the condition of magnetic stirring, controlling the temperature of the water bath to be 50 ℃, adding the mixed oil phase into 100g of water, and stirring for 10min to obtain a beta-carotene water dispersion, wherein the content of the beta-carotene in the prepared transparent water dispersion is 2%.

The nano emulsion prepared by the embodiment has clear and transparent appearance and the average particle size of about 41 nm.

Example 5:

weighing 4g of beta-carotene, 10g of lecithin, 6g of polyethylene glycol 400 and 0.15g of tert-butylhydroquinone, heating to 190 ℃ for melting, and uniformly mixing by vortex oscillation to obtain a mixed solution. Adding the mixed solution into 100g of purified water, placing the mixture into a water bath at 50 ℃ for magnetic stirring for 10min, and then carrying out ultrasonic treatment at 150W for 10min to obtain a beta-carotene water dispersion, wherein the content of beta-carotene in the prepared transparent water dispersion is 4%.

The nano emulsion prepared by the embodiment has clear and transparent appearance and average particle size of about 75 nm.

Example 6:

weighing 5g of beta-carotene, 25g of polyoxyethylene hydrogenated castor oil and 0.5g of butyl hydroxy anisole, heating to 190 ℃ for melting, and uniformly mixing by vortex oscillation to obtain a mixed solution. The rotating speed of the super-gravity rotating bed is 2000rpm, the mixed oil phase is fed at 3ml/min, the pre-preheated purified water is fed at 300ml/min, the temperature of the system is controlled at 50 ℃, after the mixed solution is fed, the super-gravity rotating bed is closed, the beta-carotene water dispersion is obtained, and the content of the beta-carotene in the prepared transparent water dispersion is 0.2%.

The nano emulsion prepared by the embodiment has clear and transparent appearance and average particle size of about 25 nm.

Example 7

The stability of the aqueous dispersions prepared was tested:

the stability test method comprises the following steps: according to 9001-guideline for stability experiment of raw material drugs and preparation in pharmacopoeia of China (2015 edition), 3 batches of beta-carotene emulsion prepared in each example and comparative example are placed in brown screw bottles, placed for 1 month at room temperature and 4 ℃, sampled for 7 days, 14 days and 30 days, and tested for particle size change and content change by High Performance Liquid Chromatography (HPLC) using a laser particle sizer (Malvern Zetasizer Nano ZS 90).

FIG. 3 shows the results of the content stability of the transparent aqueous dispersions of beta-carotene obtained in the examples of the present invention and the comparative examples, when they were left at 4 ℃ for 30 days. As is clear from the graphs, the aqueous dispersions obtained in examples 1 to 6 were stable under these conditions, and all of them did not change much within 30 days.

FIG. 4 shows the results of the content stability of the transparent aqueous dispersions of beta-carotene obtained in the examples of the present invention and the comparative examples after 30 days at room temperature. As is clear from the graphs, the aqueous dispersions obtained in examples 1 to 6 were stable under these conditions, and all of them did not change much within 30 days.

Fig. 7 shows the form of the aqueous dispersion of β -carotene obtained in examples 1 and 2 and comparative examples 1 and 2 after 30 days at room temperature, and it can be seen that the dispersions obtained in examples 1 and 2 are still clear and transparent, while the dispersions obtained in comparative examples 1 and 2 are turbid and have poor transparency.

In conclusion, the method for preparing the transparent aqueous dispersion of beta-carotene, provided by the invention, can finally prepare the nano emulsion with the particle size less than 100nm, and clear and transparent appearance through the synergistic cooperation of each reaction step and corresponding reaction conditions.

It should be understood that the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention, and it will be obvious to those skilled in the art that other variations or modifications may be made on the basis of the above description, and all embodiments may not be exhaustive, and all obvious variations or modifications may be included within the scope of the present invention.

Claims

1. The transparent beta-carotene water dispersion is characterized by comprising the following components in percentage by mass:

2. the transparent aqueous dispersion of beta-carotene according to claim 1, characterized in that it comprises the following components in percentage by mass:

3. the transparent aqueous dispersion of β -carotene according to claim 1, wherein said emulsifier is selected from one or more of tween 20, tween 80, span 80, polyoxyethylene hydrogenated castor oil, castor oil polyoxyethylene ether, poloxamer, fatty acid monoglyceride, soya lecithin, egg yolk lecithin.

4. The transparent aqueous dispersion of beta-carotene according to claim 1, wherein said co-emulsifier is one or more selected from the group consisting of absolute ethanol, 1,2 propylene glycol, glycerol, n-butanol, polyethylene glycol 400.

5. A transparent aqueous dispersion of beta-carotene according to claim 1, wherein said antioxidant is selected from one or more of vitamin E, antioxidant quinoline, butylated hydroxyanisole, 2, 6-di-tert-butyl-4-methylphenol, and tert-butylhydroquinone.

6. Transparent aqueous dispersion of beta-carotene according to claim 1, characterized in that the mass ratio of the emulsifier to co-emulsifier is 1:5-5:1, preferably 1:2-2: 1; the weight ratio of the beta-carotene to the total of the emulsifier and the co-emulsifier is 1:15-1:0.5, preferably 1:5-1: 1.

7. A process for the preparation of a transparent aqueous dispersion of β -carotene according to any one of claims 1 to 6, comprising the steps of:

8. The method of claim 7, wherein the melting temperature is 180 ℃ to 200 ℃.

9. The preparation method according to claim 7, wherein the emulsifier is one or more of a super-gravity rotating bed, an ultrasonic instrument, a microchannel reactor and a water bath with magnetic stirring;

preferably, the feed volume ratio of the mixed solution and water is 1:10 to 1:150, more preferably 1:20 to 1: 80;

preferably, the adding speed of the mixed solution to the emulsifier is 1-30ml/min, more preferably 5-10 ml/min;

preferably, the rate of addition of water to the emulsifier is from 10 to 600ml/min, more preferably from 50 to 100 ml/min.

Preferably, the rotation speed of the emulsifier is 500-.

10. The method according to claim 7, wherein the temperature at which the mixed solution and water are mixed in the emulsifier is 25 to 85 ℃, preferably 30 to 60 ℃.