CN115501168A - Construction method of double-layer soluble dietary nutrient transdermal delivery system - Google Patents
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Abstract
The invention discloses a construction method of a double-layer soluble dietary nutrient transdermal delivery system, which comprises the steps of pretreating macromolecular nutrient substances through a biological method to obtain skin-friendly and easily absorbed micromolecular nutrient substances as nutrient raw materials of the transdermal delivery system, further preparing a soluble needle-shaped micro-tube with the diameter of 200 mu m and the length of 600 mu m capable of penetrating through a skin cuticle by a template method, opening a passage for delivering the nutrient substances, wherein the double-layer soluble needle-shaped micro-tube comprises two matrix materials with different dissolution rates, the tip matrix material comprises rapidly-dissolved chitosan and glucan as the matrix materials, the tail matrix material adopts the slowly-dissolved transparent material, glucose is wrapped in the tip matrix material, and the nutrients such as protein, fat and short-chain fatty acid are wrapped in the tail matrix material to form a mode of differential release of the nutrient substances, so as to continuously provide energy for a human body.
Description
Technical Field
The invention relates to the technical field of dietary nutrient delivery in the fields of modern agriculture and food, in particular to a construction method of a double-layer soluble dietary nutrient transdermal delivery system.
Background
At present, in addition to energy supplementation by diet, nutrition supplementation by intravenous injection forms a second channel of human nutrition supplementation. Aiming at the problem that the body is inconvenient to supplement energy by eating and injecting under special working environment, a new energy supply way for the body needs to be developed urgently. Based on agricultural raw materials, the method of adopting novel biotechnology, big data analysis technology, emerging industrial technology and the like to design and manufacture functional products in a targeted manner has become a future trend; emphasizing the precise nutrition of an individual will necessarily be the next goal pursued by human beings. People of different sexes, ages, working environments and physiological conditions have different requirements for the intake of nutrients, and therefore, different forms of nutritional supplements are required. In some special environments (such as high-temperature environment, plateau environment, war state, space environment and medical industry) and special physiological states (such as incapability of independently eating), people who are specially needed have the current situation of difficult eating, so that the development of energy supplement ways except diet or injection becomes an urgent problem to be solved.
Disclosure of Invention
The technical problem to be solved by the invention is to overcome the technical defects and provide a construction method of a double-layer soluble dietary nutrient transdermal delivery system, which pretreats macromolecular nutrient substances by a biological method to obtain skin-friendly and easily absorbed micromolecular nutrient as a nutrient raw material of the transdermal delivery system; furthermore, a soluble needle-shaped microtubule which has the diameter of 200 mu m and the length of 600 mu m and can penetrate through the stratum corneum of the skin is prepared by a template method, so as to open a passage for delivering nutrients; meanwhile, a double-layer structure of the soluble needle-shaped microtubules is constructed by adopting different materials, so that the dietary nutrients are released in a differential manner.
In order to solve the technical problems, the technical scheme provided by the invention is as follows: a method for constructing a double-layer soluble dietary nutrient transdermal delivery system, wherein the double-layer soluble needle type microtubule consists of matrix materials with two different dissolution rates, a tip matrix material is made of rapidly-dissolved chitosan and glucan as the matrix materials, a tail matrix material is made of slowly-dissolved hyaluronic acid, glucose is wrapped in the tip matrix material, nutrients such as protein, fat and short-chain fatty acid are wrapped in the tail matrix material to form a form of differential release of the nutrients, and energy is continuously provided for a human body, and the method comprises the following steps:
1) Preparing a template:
mixing the polydimethylsiloxane prepolymer and the curing agent in a ratio of 10:1, pouring the mixture into a mold, heating the mixture at 60 ℃ for 1 hour for curing to obtain a PDMS sheet, setting parameters of a laser engraving machine, and engraving the PDMS sheet by laser to obtain a PDMS template with the height of 600 microns, the bottom diameter of 300 microns and the central distance between adjacent microtubes of about 800 microns;
2) Preparing the double-layer needle type microtube:
a. preparing a tip matrix material: preparing 5% (w/v) acetic acid solution of chitosan; dissolving 1g of the dextran solution in 2mL of water to prepare a dextran solution; mixing the prepared chitosan solution and the prepared glucan solution according to the weight ratio of 1:1 (v/v), adding nutrient 50% glucose into the mixed solution to form a tip matrix material;
b. preparing a tail end matrix material: mixing nutrients such as lactalbumin, short-chain fatty acid and glycerol with hydroxypropyl-beta-cyclodextrin, and mixing with hyaluronic acid at a ratio of (2;
c. preparing a sealing film solution: preparing 30% (w/v) polyvinylpyrrolidone K90 solution;
3) Construction of a transdermal delivery system for dietary nutrients:
200 μ L of the tip matrix material was added to the PDMS template, centrifuged at 4000rpm for 5min at 4 ℃ to completely fill the tip of the mold with the solution, then excess solution was removed from the mold surface, followed by addition of the tail matrix material, centrifuged in the same manner, finally 200 μ L of the cap liner solution was added, dried by centrifugation in the same manner, and then demolded.
PDMS templates with different specifications can be prepared by adjusting machine parameters in the step 1).
In the step 2), needle-shaped microtubes with different nutrient loads can be prepared by adjusting the types and the addition amount of the nutrients, and the mechanical strength of the needle-shaped microtubes can also be adjusted by adjusting the ratio of the nutrients to the matrix material.
Compared with the prior art, the invention has the advantages that: 1) Delivering the dietary nutrients to the body through the skin, and developing a novel nutrient absorption mode.
2) The nutrient is released at different speed, glucose is released quickly to relieve hunger sensation, and protein, fatty short-chain fatty acid and the like are released slowly to supply energy continuously, so that energy supplement can be provided for people who cannot eat food in time at any time.
Of course, it is not necessary for any one product in which the invention is practiced to achieve all of the above-described technical effects simultaneously.
Drawings
Fig. 1 is a schematic diagram of a soluble needle-type microtubule energy supplement patch in example 1 of a method for constructing a bilayer soluble dietary nutrient transdermal delivery system according to the present invention.
Fig. 2 is a schematic diagram of a double-layer soluble dietary nutrient transdermal delivery system in an embodiment 2 of the construction method of the double-layer soluble dietary nutrient transdermal delivery system.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings.
The invention discloses a construction method of a double-layer soluble dietary nutrient transdermal delivery system, which comprises the following steps:
1) Polydimethylsiloxane (PDMS) prepolymer was mixed with curing agent in a 10:1, and pouring the mixture into a mould;
2) And (2) placing the mixture obtained in the step 1) in a thermostat at 60 ℃ for heating for 1h for curing to obtain the PDMS sheet.
3) And (3) placing the obtained product in the step 2) in a laser engraving machine, setting parameters of the laser engraving machine to be 600 micrometers in height, 300 micrometers in bottom diameter and 800 micrometers in center distance between two adjacent micro-tubes to obtain the PDMS template.
4) Chitosan (CS) was added to a 1% acetic acid solution and stirred until clear, yielding a 5% (w/v) chitosan-acetic acid solution.
5) Add 1g of Dextran (DEX) to 2mL of deionized water, stir at room temperature, and mix well.
6) Mixing the solution obtained in the step 4) and the solution obtained in the step 5) according to the ratio of 1:1 volume ratio and mixing evenly.
7) Adding 50% glucose into the solution obtained in the step 6), mixing uniformly, and standing at room temperature to remove air bubbles in the solution.
8) The nutritional energy supply components of protein, fat and short-chain fatty acid are proportioned according to the proportion of 6.
9) Mixing the solution obtained in the step 8) with Hyaluronic Acid (HA) in a ratio of 2:1 (v/w) was mixed uniformly.
10 Prepare 30% (w/v) polyvinylpyrrolidone (PVPK 90) solution.
11 200. Mu.L of the solution obtained in step 7) was added to the template obtained in step 2), centrifuged at 4000rpm for 5min at 4 ℃ and then the excess solution on the surface of the mold was removed.
12 The solution obtained in step 9) was added to the sample prepared in step 11) so that the solution filled the entire mold cavity, and centrifuged at 4000rpm for 5min at 4 ℃ to remove excess solution from the mold surface.
13 200 μ L of the solution obtained in the step 10) is added to the sample obtained in the step 12), and the mixture is centrifuged for 3min to remove the excessive solution, and after standing and drying, the mixture is demoulded.
In the steps, the setting parameters of the template micro-needle can be changed according to different nutrient demands, and the glucose concentration or the proportion of protein, fat and short-chain fatty acid can be changed according to different nutrient demands.
The invention has the advantages that the dietary nutrients are creatively delivered to the body through the needle-shaped microtubule technology to realize nutritional energy supply, the glucose is quickly released in the body by utilizing the differential release technology to relieve hunger sensation, and meanwhile, the nutrients such as protein, fat and short-chain fatty acid are slowly released to continuously provide energy for the body. The method provides a new way for the absorption of nutrients of human body.
The present application will be described in more detail with reference to examples below to facilitate understanding by those skilled in the art.
In the steps, the nutrients are prepared by self fermentation in the laboratory, the preparation and raw materials are all commercial products, and the instruments or equipment are all common instruments or equipment in the laboratory.
EXAMPLE 1 preparation of soluble needle-type microtube energy supplement Patch
1) Preparing a template: mixing polydimethylsiloxane prepolymer and curing agent in a ratio of 10:1, pouring the mixture into a mold, and heating the mixture for 1 hour at the temperature of 60 ℃ for curing to obtain the PDMS sheet. Setting parameters of a laser engraving machine, and obtaining the PDMS template with the height of 600 microns, the diameter of the bottom of 300 microns and the center distance between adjacent microtubes of about 800 microns through laser engraving.
2) Preparing a needle type microtube: preparing an acetic acid solution of 5% (w/v) Chitosan (CS) by band-pass, simultaneously dissolving 1g of Dextran (DEX) solution in 2mL of water to prepare a dextran solution, and mixing the two solutions in the following steps according to the ratio of 1:1 (v/v) after mixing, 50% glucose was added to the above mixed solution to form a tip matrix material.
3) Construction of a transdermal delivery system for dietary nutrients: 200 μ L of tip matrix material was added to the PDMS template and centrifuged at 4000rpm for 5min at 4 ℃ to completely fill the tips of the mold with the solution, followed by removal of excess solution from the mold surface. Subsequently, hyaluronic acid was added as a tail matrix material, filling the mold cavity, and centrifugation was performed in the same manner. Finally, 200. Mu.L of a 30% (w/v) polyvinylpyrrolidone (PVP K90) solution was added, and after centrifugal drying in the same manner, the plate was removed for use. As shown in fig. 1, a soluble needle-type microtubule energy-supplementing patch was obtained.
Example 2 preparation of a double-layer soluble needle-type microtubule total nutrient dietary supplement patch.
1) Preparing a template: mixing the polydimethylsiloxane prepolymer and the curing agent in a ratio of 10:1, pouring the mixture into a mold, and heating the mixture for 1 hour at the temperature of 60 ℃ for curing to obtain the PDMS sheet. Setting parameters of a laser engraving machine, and obtaining the PDMS template with the height of 600 microns, the diameter of the bottom of 300 microns and the center distance between adjacent microtubes of about 800 microns through laser engraving.
2) Preparing a double-layer needle type microtube: preparing an acetic acid solution of 5% (w/v) Chitosan (CS) by band-pass, simultaneously dissolving 1g of Dextran (DEX) solution in 2mL of water to prepare a dextran solution, and mixing the two solutions in the following steps according to the ratio of 1:1 (v/v) after mixing, 50% glucose was added to the above mixed solution to form a tip matrix material. Mixing the high-F-value oligopeptide, the liposome amino acid and the short-chain fatty acid with hyaluronic acid according to the proportion of 6: 1 (v/w) to obtain a tail-end matrix material.
3) Construction of a transdermal delivery system for dietary nutrients: 200 μ L of tip matrix material was added to the PDMS template and centrifuged at 4000rpm for 5min at 4 ℃ to completely fill the tip of the mold with the solution, followed by removal of excess solution from the mold surface. Subsequently, hyaluronic acid was added as a tail-end matrix material, and centrifuged in the same manner. Finally, 200. Mu.L of a 30% (w/v) polyvinylpyrrolidone (PVP K90) solution was added, and after centrifugal drying in the same manner, the plate was removed for use. As shown in figure 2, the needle-shaped microtubule double-layer soluble full-nutrition dietary nutrient transparent patch is obtained.
The invention discloses a construction method of a double-layer soluble dietary nutrient transdermal delivery system. Creates a construction method of a soluble differential release needle type microtubule dietary nutrient delivery system, realizes the purpose of transdermal delivery of dietary nutrients, and opens up a new way for supplying nutrition to organisms.
While the foregoing description shows and describes several preferred embodiments of the invention, it is to be understood, as noted above, that the invention is not limited to the forms disclosed herein, but is not to be construed as excluding other embodiments and is capable of use in various other combinations, modifications, and environments and is capable of changes within the scope of the inventive concept as expressed herein, commensurate with the above teachings, or the skill or knowledge of the relevant art. And that modifications and variations may be effected by those skilled in the art without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (3)
1. A construction method of a double-layer soluble dietary nutrient transdermal delivery system is characterized by comprising the following steps: different materials are adopted, a two-stage template method is adopted to prepare a soluble needle-shaped microtubule which has the diameter of 200 mu m and the length of 600 mu m and can penetrate the stratum corneum of the skin, an access is opened for delivering nutrients, and differential release is realized, and the method comprises the following steps:
1) Preparing a template:
mixing polydimethylsiloxane prepolymer and curing agent in a ratio of 10:1, pouring the mixture into a mold, heating the mixture at 60 ℃ for 1 hour for curing to obtain a PDMS sheet, setting parameters of a laser engraving machine, and engraving the PDMS sheet by laser to obtain a PDMS template with the height of 600 microns, the bottom diameter of 300 microns and the central distance between adjacent microtubes of about 800 microns;
2) Preparing a double-layer needle type microtube:
a. preparing a tip matrix material: preparing 5% (w/v) acetic acid solution of chitosan; dissolving 1g of the dextran solution in 2mL of water to prepare a dextran solution; mixing the prepared chitosan solution and the prepared glucan solution according to the weight ratio of 1:1 (v/v), adding nutrient 50% glucose into the mixed solution to form a tip matrix material;
b. preparing a tail end matrix material: mixing nutrients such as lactalbumin, short-chain fatty acid and glycerol with hydroxypropyl-beta-cyclodextrin, and mixing with hyaluronic acid at a ratio of (2;
c. preparing a sealing film solution: preparing 30% (w/v) polyvinylpyrrolidone K90 solution;
3) Construction of a transdermal delivery system for dietary nutrients:
200 μ L of the tip matrix material was added to the PDMS template, centrifuged at 4000rpm for 5min at 4 ℃ to completely fill the tips of the mold with the solution, followed by removal of excess solution from the mold surface, followed by addition of the tail matrix material, centrifuged in the same manner, and finally 200 μ L of the cap patch solution was added, centrifuged in the same manner, dried, and demolded.
2. The method of constructing a bi-layer transdermal soluble dietary nutrient delivery system of claim 1, wherein: PDMS templates with different specifications can be prepared by adjusting the parameters of the machine in the step 1).
3. The method of constructing a bi-layer transdermal delivery system for soluble dietary nutrients as claimed in claim 1, wherein: in the step 2), needle-shaped microtubes with different nutrient loading amounts can be prepared by adjusting the types and the addition amount of the nutrients, and the mechanical strength of the needle-shaped microtubes can also be adjusted by adjusting the ratio of the nutrients to the matrix material.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109069815A (en) * | 2016-04-05 | 2018-12-21 | 株式会社 Lg 生活健康 | Microneedle configuration for effective skin punctures |
| CN114569583A (en) * | 2022-03-14 | 2022-06-03 | 中山大学 | Rapid separation type liposome composite sustained-release microneedle and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109069815A (en) * | 2016-04-05 | 2018-12-21 | 株式会社 Lg 生活健康 | Microneedle configuration for effective skin punctures |
| CN114569583A (en) * | 2022-03-14 | 2022-06-03 | 中山大学 | Rapid separation type liposome composite sustained-release microneedle and preparation method thereof |
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