THERMOSENSITIVE NANOCAPSULES AND PREPARING METHOD THEREOF

• US 20190329211A1
• Filed: 07/01/2016
• Published: 10/31/2019
• Est. Priority Date: 06/29/2016
• Status: Active Grant

• Current Assignee: Anhui Microdelivery Smart Microcapsule Sci & Tech Co. Ltd
• Original Assignee: Anhui Microdelivery Smart Microcapsule Sci & Tech Co. Ltd
• Inventors: LU, Xihua, ZHAO, Di, WANG, Liying
• Granted Patent: US 10,543,471 B2
• Time in Patent Office: Days
• CPC Class Codes: A23L 27/72 Encapsulation
• CPC Class Codes: A23L 27/74 with a synthetic polymer matrix or excipient, e.g. vinylic, acrylic polymers
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A61K 2800/10 General cosmetic use
• CPC Class Codes: A61K 2800/412 Microsized, i.e. having sizes between 0.1 and 100 microns
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 8/11 Encapsulated compositions
• CPC Class Codes: A61K 8/35 Ketones, e.g. benzophenone
• CPC Class Codes: A61K 8/37 Esters of carboxylic acids
• CPC Class Codes: A61K 8/40 containing nitrogen quinones containing nitrogen A61K8/355
• CPC Class Codes: A61K 8/8158 Homopolymers or copolymers of amides or imides, e.g. (meth) acrylamide; Compositions of derivatives of such polymers
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61Q 13/00 : Formulations or additives for perfume preparations essential oils or perfumes per se C11B9/00
• CPC Class Codes: A61Q 17/04 : Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: B01J 13/025 : Applications of microcapsules not provided for in other subclasses
• CPC Class Codes: B01J 13/185 : in an organic phase
• CPC Class Codes: C11B 9/0003 : Compounds of unspecified constitution defined by the chemical reaction for their preparation

Abstract

The present invention discloses a thermosensitive nanocapsule and a preparing method thereof. The thermosensitive nanocapsule includes core materials and wall materials. The preparing method includes: first, making water phase and oil phase respectively, forming microemulsion by means of high speed shearing after mixing, and forming nanoemulsion via ultrasonic treatment or high pressure homogenization; then adding nitrogen to the emulsion and carrying out the reaction under a temperature of 40-80° C. for 3-4 hrs in the nitrogen atmosphere; finally obtaining the thermosensitive nanocapsule with an embedding rate of 90-94%, a particle size of less than 150 nm and a dimension polydispersity index of 0.09-0.17. In present invention, the monomer that forms the wall material of the nanocapsules is made from common biological materials, and has a good biocompatibility. The wall material has a temperature sensitivity, and can control the delayed release of core material by adjusting temperature.

Claims

1. A method for preparing thermosensitive nanocapsules, wherein the thermosensitive nanocapsules are prepared by forming a wall material from a free radical polymerization of two different N-alkyl acrylamide monomers;

the method comprises the following steps;

(1) making an emulsifier aqueous solution by mixing an emulsifier and deionized water to form a water phase;

(2) mixing and fully stirring a core material, the two different N-alkyl acrylamide monomers, a crosslinking agent, an initiator and a co-stabilizer to form an oil phase;

(3) adding the water phase to the oil phase, forming microemulsion by shearing, and then forming a nanoemulsion via sonication; and

(4) introducing nitrogen into the nanoemulsion and carrying out a reaction at 40-80°

C., finally obtaining the thermosensitive nanocapsules;

wherein the two N-alkyl acrylamide have a general formula of

2. The method of claim 1, wherein the emulsifier is selected from the group consisting of sodium dodecyl sulfonate, arabic gum and polyvinyl alcohol with a hydrolysis degree of 80-90%.

3. The method of claim 1, wherein the core material is one or more selected from the group consisting of an ultraviolet absorber, a flavor or a fragrance, a phase change material and a pharmaceutical, wherein the ultraviolet absorbent is selected from the group consisting of octocrylene, benzophenone-3, octyl salicylate, avobenzone and iso-octyl methoxycinnamate;

the flavor or the fragrance is selected from the group consisting of peppermint oil, rose flavor, lemon flavor, lavender flavor, green tea flavor, lotus flavor and flower fragrance;

the phase change material is selected from the group consisting of paraffin, n-tetradecane, n-pentadecane, n-hexadecane, n-heptadecane, n-octadecane, n-nonadecane, n-eicosane, n-heneicosane, n-docosane, n-tricosane and n-tetracosane; and

the pharmaceutical is selected from the group consisting of vitamin oil and antineoplastic drugs.

4. The method of claim 1, wherein the N-alkyl acrylamide monomer is selected from the group consisting of N,N-diethyl acrylamide, N,N-dimethyl acrylamide, N-isopropyl acrylamide, N-ethyl acrylamide, N-tert-butyl acrylamide, N-n-propyl acrylamide and N-methyl-N-ethyl acrylamide.

5. The method of claim 1, wherein the crosslinking agent is one or more selected from the group consisting of ethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate and 1,6-hexanediol dimethacrylate.

6. The method of claim 1, wherein the initiator is selected from the group consisting of azobisisobutyronitrile or benzoyl peroxide, and the co-stabilizer is selected from the group consisting of hexadecane, hexadecanol and octadecyl mercaptan.

7. The method of claim 1, wherein the water phase and the oil phase are counted by weight parts, and possess a composition of

1.5-4.5 phr of the emulsifier;

10-90 phr of the deionized water;

10-120 phr of the core material;

6-14 phr of a first acrylamide from the two N-alkyl acrylamide;

6-14 phr of a second acrylamide from the two N-alkyl acrylamide;

1-5 phr of the crosslinking agent;

0.1-0.8 phr of the initiator; and

1-2.5 phr of the co-stabilizer.

8. The method of claim 1, wherein the shearing has a rate of 6000˜

10000 rpm and a time of 3-6 min, and the sonication has an amplitude of 50% and a time of 10-30 min.

9. The method of claim 1, wherein the step of introducing nitrogen means maintaining the protection nitrogen atmosphere for the nanoemulsion system till the ending of reaction, and the reaction has a time of 3-4 hr.

10. A thermosensitive nanocapsule, prepared by the method of claim 1, comprising the core material and the wall material, wherein

the core material embedded in the wall material;

the wall material is formed through the free radical polymerization in a water and oil interface of the two N-alkyl acrylamide monomers from the oil phase;

the thermosensitive nanocapsule has an embedding rate of 90-94%, a particle size of less than 150 nm and a dimension polydispersity index of 0.09-0.17.

11. The thermosensitive nanocapsule of claim 10, wherein the emulsifier is selected from the group consisting of sodium dodecyl sulfonate, arabic gum and polyvinyl alcohol with a hydrolysis degree of 80-90%.

12. The thermosensitive nanocapsule of claim 10, wherein the core material is one or more selected from the group consisting of an ultraviolet absorber, a flavor or a fragrance, a phase change material and a pharmaceutical, wherein the ultraviolet absorbent is selected from the group consisting of octocrylene, benzophenone-3, octyl salicylate, avobenzone and iso-octyl methoxycinnamate;

the flavor or fragrance is selected from the group consisting of peppermint oil, rose flavor, lemon flavor, lavender flavor, green tea flavor, lotus flavor and flower fragrance;

the phase change material is selected from the group consisting of paraffin, n-tetradecane, n-pentadecane, n-hexadecane, n-heptadecane, n-octadecane, n-nonadecane, n-eicosane, n-heneicosane, n-docosane, n-tricosane and n-tetracosane; and

the pharmaceutical is selected from the group consisting of vitamin oil and antineoplastic drugs.

13. The thermosensitive nanocapsule of claim 10, wherein the N-alkyl acrylamide monomer is selected from the group consisting of N,N-diethyl acrylamide, N,N-dimethyl acrylamide, N-isopropyl acrylamide, N-ethyl acrylamide, N-tert-butyl acrylamide, N-n-propyl acrylamide and N-methyl-N-ethyl acrylamide.

14. The thermosensitive nanocapsule of claim 10, wherein the crosslinking agent is one or more selected from the group consisting of ethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate and 1,6-hexanediol dimethacrylate.

15. The thermosensitive nanocapsule of claim 10, wherein the initiator is selected from the group consisting of azobisisobutyronitrile and benzoyl peroxide, and the co-stabilizer is one selected from the group consisting of hexadecane, hexadecanol and octadecyl mercaptan.

16. The thermosensitive nanocapsule of claim 10, wherein the water phase and the oil phase are counted by weight parts, and have a composition of

1.5-4.5 phr of the emulsifier;

10-90 phr of the deionized water;

10-120 phr of the core material;

6-14 phr of a first acrylamide of the two N-alkyl acrylamide;

6-14 phr of a second acrylamide of the two N-alkyl acrylamide;

1-5 phr of the crosslinking agent;

0.1-0.8 phr of the initiator; and

1-2.5 phr of the co-stabilizer.

17. The thermosensitive nanocapsule of claim 10, wherein the shearing has a rate of 6000˜

10000 rpm and a time of 3-6 min, and the sonication has an amplitude of 50% and a time of 10-30 min.

18. The thermosensitive nanocapsule of claim 10, wherein the step of introducing nitrogen means maintaining the protection nitrogen atmosphere for the nanoemulsion system till the ending of reaction, and said reaction has a time of 3-4 hr.