CN114404386A - Microelement-loaded yeast micro-nano robot sugar pill and preparation method thereof - Google Patents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6901—Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
Abstract
The invention provides a yeast micro-nano robot sugared pill loaded with trace elements, which is characterized by comprising an external polysaccharide capsid and at least one internal yeast micro-nano robot, wherein the yeast micro-nano robot consists of yeast cells, biological enzymes covered on the yeast cells in a half-surface mode and the trace elements loaded in the yeast cells. The polysaccharide capsid of the yeast micro-nano robot sugar pill can be degraded in an intestinal tract to release the yeast micro-nano robot carrying trace elements, and the yeast micro-nano robot can autonomously move by using glucose in the intestinal tract as power, so that the yeast micro-nano robot can penetrate through barriers such as a mucus barrier and an epithelial barrier to reach the intestinal wall, and the absorption of trace elements by an organism is efficiently promoted.
Description
Technical Field
The invention belongs to the technical field of drug carriers, and particularly relates to a yeast micro-nano robot sugar pill loaded with trace elements and a preparation method thereof.
Background
Although trace elements are very small in proportion in human bodies, the trace elements have a very large effect in the physiological activities of the human bodies. If the trace elements are lacked for a long time, various diseases can be caused. Such as iron deficiency anemia, statins caused by iodine deficiency, endemic goiter, low immunity caused by selenium deficiency, and the like. Excessive intake of trace elements also causes diseases, so efficient and accurate intake of trace elements is very important. Research shows that the direct supplement of inorganic trace elements has low activity and short in-vivo retention time, so that the trace element supplement efficiency is low, and the dosage cannot be accurately controlled.
Yeast cells are well recognized safe edible probiotics that have the ability to efficiently fix trace elements. However, after the yeast cells rich in trace elements are taken orally, the yeast cells can enter the intestinal wall by overcoming the resistance of evacuation movement of the intestinal cavity, intestinal mucus barriers, intestinal epithelial barriers and the like, so that the trace elements are released and utilized by a human body. And the yeast cannot move, so that the barrier effect is difficult to break through, and the absorption efficiency is limited.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a yeast micro-nano robot sugar pill loaded with trace elements and a preparation method thereof. The polysaccharide capsid of the yeast micro-nano robot sugar pill can be degraded in an intestinal tract to release a group of yeast micro-nano robots loaded with trace elements, and the yeast micro-nano robots can independently cluster and move by using a cluster effect and decomposing glucose in the intestinal tract as power, so that the yeast micro-nano robots penetrate through barriers such as mucus barriers and epithelial barriers to reach the intestinal wall, and the absorption of trace elements by organisms is efficiently promoted.
The method is realized by the following technical scheme:
the yeast micro-nano robot dragee loaded with trace elements comprises an external polysaccharide capsid and an internal yeast micro-nano robot, wherein the yeast micro-nano robot is composed of yeast cells, biological enzymes partially covered on the yeast cells and trace elements loaded in the yeast cells.
Further, the components of the polysaccharide shell are one or more of lactose, maltose, sucrose, dextrin, starch, fructose, xylose or microcrystalline cellulose.
Further, the biological enzyme is glucose oxidase and catalase.
Further, the trace elements are one or more of calcium, iron, zinc, selenium, copper, molybdenum, chromium, cobalt, iodine, fluorine and manganese.
The invention also provides a preparation method of the trace element loaded yeast micro-nano robot dragee, which is characterized by comprising the following steps:
(1) recovering the yeast cells to enable the yeast cells to have respiration and generate carbon dioxide inside the cells;
(2) mixing the yeast cells recovered in the step (1) with a trace element salt solution, incubating, and carrying out biomineralization to obtain trace element-loaded yeast cells;
(3) mixing the yeast cells carrying the trace elements with a masking agent, drying, and removing the redundant masking agent to obtain partially masked yeast cells;
(4) adding an activating agent into the partially masked yeast cells obtained in the step (3) for activation, and removing unreacted activating agent after activation to obtain partially activated yeast cells;
(5) adding glucose oxidase and catalase into the partially activated yeast cells obtained in the step (4) for reaction, and removing unbound enzyme after reaction to obtain the trace element-loaded yeast micro-nano robot;
(6) and (4) mixing polysaccharide with the yeast micro-nano robot loaded with the trace elements in the step (5), and then preparing into a sugar pill to obtain the yeast micro-nano robot loaded with the trace elements.
Preferably, the mass ratio of the trace element-loaded yeast cells to the masking agent in step (3) is 1 (0.01-0.25), and the mass ratio of the partially masked yeast cells to the activating agent in step (4) is 1 (40-80).
Preferably, in the step (5), the mass ratio of the catalase to the glucose oxidase is 1 (2-5). Glucose oxidase takes glucose in vivo as a substrate, the glucose is oxidized into gluconic acid and hydrogen peroxide, hydrogen peroxide is decomposed into water and oxygen by catalase, and the two enzyme reactions are cascade reactions. At this mass ratio, however, the two enzyme cascades are sufficient to provide sufficient driving force.
Preferably, in the step (6), the mass ratio of the yeast micro-nano robot to the polysaccharide is 1 (50-200).
Preferably, the temperature of the reaction is 4 ℃ to 25 ℃, and the duration of the reaction is 16 to 24 hours.
The yeast micro-nano robot provided by the invention can be used for preparing a medicine for treating diseases caused by trace element deficiency.
The beneficial effects of the invention comprise the following aspects:
1. edible fungus yeast cells are used as carriers, so that the edible fungus yeast cells are green and safe and can be widely used for food and medicine;
2. the yeast micro-nano robot can actively move, break through the intestinal barrier and has more efficient drug delivery;
3. the yeast micro-nano robot pill aggregates a plurality of or single yeast micro-nano robots together, the pills in the intestinal tract are degraded, the yeast micro-nano robot clusters move, and the drug delivery efficiency is further improved.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
FIG. 1 is a schematic structural diagram of a yeast micro-nano robot sugar pill loaded with trace elements;
FIG. 2 is a schematic diagram and a physical diagram of preparation of a yeast micro-nano robot sugar pill loaded with trace elements;
fig. 3 is a comparison diagram of motion trajectories of unmodified yeast cells and trace element-loaded yeast micro-nano robot pellets prepared in the embodiment of the present invention, where fig. 3(1) is a diagram of motion trajectories of unmodified yeast cells, and fig. 3(2) is a diagram of motion trajectories of trace element-loaded yeast micro-nano robot pellets;
FIG. 4 is an image of trace element-loaded yeast micro-nano robot pellets reaching the intestinal tract;
FIG. 5 is a data statistical chart of the oral administration of yeast cells, a single microelement-loaded yeast micro-nano robot and microelement-loaded yeast micro-nano robot pellets in the intestinal tract;
fig. 6 is a HE diagram of the safety of the yeast micro-nano robot dragee loaded with trace elements to intestinal tracts after being orally taken.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Researches show that the trace elements are adsorbed on the outer surface of the micro-nano robot, and the micro-nano robot is pushed to actively move to the stomach by gas generated by the reaction of enzyme in gastric acid, so that the absorption efficiency of the trace elements is greatly increased. In addition, the clustering effect of the micro-nano robot is far greater than the action effect of a single micro-nano robot. If a single micro-nano robot cannot cross a barrier, a group of micro-nano robots can easily bypass the barrier, and more interestingly, half of the robots capable of moving and the robots incapable of moving are mixed together, and all particles can move. Therefore, the medicine feeding efficiency can be greatly improved by utilizing the cluster movement phenomenon.
The invention provides a yeast micro-nano robot sugared pill loaded with trace elements, which comprises an external polysaccharide capsid and at least one internal yeast micro-nano robot, wherein the yeast micro-nano robot consists of yeast cells, biological enzymes partially covered on the yeast cells and trace elements loaded in the yeast cells. The polysaccharide capsid of the yeast micro-nano robot sugar pill can be degraded in the intestinal tract to release the yeast micro-nano robot carrying the trace elements, and the yeast micro-nano robot can autonomously move by using glucose in the intestinal tract as power, so that the yeast micro-nano robot can penetrate through barriers such as a mucus barrier and an epithelial barrier to reach the intestinal wall, and the absorption of trace elements by an organism is efficiently promoted.
In some specific embodiments, the components of the polysaccharide shell can be one or more of lactose, maltose, sucrose, dextrin, starch, fructose, xylose, microcrystalline cellulose. The polysaccharides can be degraded in vivo, so that the yeast micro-nano robot in the capsid can be released.
Further, the biological enzymes are glucose oxidase and catalase. Glucose oxidase can decompose glucose in intestinal tracts into gluconic acid and hydrogen peroxide, catalase further decomposes the hydrogen peroxide into water and oxygen, and the two enzymes carry out cascade reaction, so that power is provided for the yeast micro-nano robot, and the yeast micro-nano robot can move autonomously.
In some embodiments, the trace element is one or more of calcium, iron, zinc, selenium, copper, molybdenum, chromium, cobalt, iodine, fluorine, and manganese, which can meet the body's needs for different trace element species.
The invention also provides a preparation method of the trace element loaded yeast micro-nano robot sugar pill, which comprises the following steps:
(1) mixing the yeast cells with a culture medium, and incubating for 0.5-1 hour at 25-37 ℃ to recover the yeast cells, so that the yeast cells can perform respiration and generate carbon dioxide inside the cells;
(2) mixing the yeast cells recovered in the step (1) with a trace element salt solution, incubating for 1-24 hours at 25-37 ℃, and performing biomineralization to obtain trace element-loaded yeast cells; the mass ratio of the yeast cells to the salt solution of the trace elements is preferably 1 (10-100);
(3) uniformly mixing the yeast cells carrying the trace elements with a masking agent, pouring the mixture into a plate, drying, and then washing with ultrapure water for three times to remove the redundant masking agent to obtain partially masked yeast cells; the mass ratio of the yeast cells carrying the trace elements to the masking agent is 1: (0.01-0.25).
(4) Adding an activating agent into the partially masked yeast cells obtained in the step (3) for activation, and removing unreacted activating agent after activation to obtain partially activated yeast cells; the activator is preferably a hydroxyl activator; the mass ratio of the yeast cells to the activating agent is 1 (40-80);
(5) adding glucose oxidase and catalase into the partially activated yeast cells obtained in the step (4), reacting for 16-24 hours at 4-25 ℃, and removing unbound enzyme after reaction to obtain the trace element-loaded yeast micro-nano robot; wherein the mass ratio of the catalase to the glucose oxidase is 1 (2-5).
(6) Mixing polysaccharide with the yeast micro-nano robot loaded with the trace elements in the step (5), and then preparing into sugar pills to obtain the yeast micro-nano robot loaded with the trace elements; the mass ratio of the yeast micro-nano robot to the polysaccharide is preferably 1 (50-200).
Examples
The yeast micro-nano robot dragee loaded with trace elements is characterized by comprising an external polysaccharide capsid and at least one internal yeast micro-nano robot, wherein the yeast micro-nano robot is composed of yeast cells, biological enzymes partially covered on the yeast cells and trace elements loaded in the yeast cells.
In some specific embodiments, the components of the polysaccharide shell can be one or more of lactose, maltose, sucrose, dextrin, starch, fructose, xylose, microcrystalline cellulose. The polysaccharides can be degraded in vivo, so that the yeast micro-nano robot in the capsid can be released.
In some embodiments, the trace element is one or more of calcium, iron, zinc, selenium, copper, molybdenum, chromium, cobalt, iodine, fluorine, and manganese, which can meet the body's needs for different trace element species.
A preparation method of a yeast micro-nano robot sugar pill loaded with trace elements comprises the following steps:
(1) mixing 10mg of yeast cells with 20mg of maltose culture medium, and incubating for 0.5-1 hour at 25-37 ℃ to recover the yeast cells, so that the yeast cells can breathe and produce carbon dioxide in the cells;
(2) mixing the recovered 10mg yeast cells with 100mg zinc chloride solution, incubating for 1-24 hours at 25-37 ℃, and performing biomineralization reaction to obtain yeast cells carrying trace elements;
(3) uniformly mixing 10mg of yeast cells carrying trace elements and 0.1mg of glycerol, pouring the mixture into a plate, drying, and then washing with ultrapure water for three times to remove redundant glycerol to obtain half-masked yeast cells;
(4) adding 40mg carbonyl diimidazole into half-masked yeast cells, and activating at room temperature for 1-2 hours; then washing with ultrapure water for three times to remove unreacted carbonyl diimidazole and obtain half-surface activated yeast cells;
(5) adding 3mg of glucose oxidase and 1mg of catalase into half-surface activated yeast cells, reacting for 16-24 hours at 4-25 ℃, and then cleaning with ultrapure water for three times to remove unbound enzyme to obtain the trace element loaded yeast micro-nano robot;
(6) 100mg of lactose/maltose (60%/40%) and 1mg of yeast micro-nano robot are uniformly mixed, put into a grinding tool and pressed into sugar pills, and the yeast micro-nano robot sugar pills loaded with trace elements are obtained.
Fig. 1 is a schematic structural diagram of a yeast micro-nano robot dragee loaded with trace elements, wherein 1 is an outer polysaccharide capsid, and 2 is an inner yeast micro-nano robot; FIG. 2 is a schematic diagram and a physical diagram of preparation of a yeast micro-nano robot dragee loaded with trace elements. And B, adding a masking agent C into the mineralized yeast cells, performing half-surface masking, adding an activating agent R, performing half-surface activation, adding a biological enzyme D, performing half-surface modification on the yeast cells, dissolving the masking agent through the step E, and finally mixing the masking agent with polysaccharide F to prepare the yeast micro-nano robot sugar pill G. H is a real object diagram of the yeast micro-nano robot dragee G.
FIG. 3 shows the microscopic recording of the movement locus of unmodified yeast cells and trace element-loaded yeast micro-nano robot pellets prepared in the embodiment of the present invention within 10s at a glucose concentration of 10 mM. FIG. 3(1) shows unmodified yeast cells, and FIG. 3(2) shows a yeast micro-nano robot. After 10 seconds, the unmodified yeast cells recorded in FIG. 3(1) were subjected to Brownian motion in situ, and the trace element-loaded yeast robot in FIG. 3(2) was moved at a distance of 30 μm and a movement speed of 3 μm/s. From the results, it can be seen that the yeast micro-nano robot can autonomously move in glucose.
Incubating 10mg of trace element-loaded yeast microcapsules or 10mg of single trace element-loaded yeast micro-nano robot or 10mg of trace element-loaded yeast micro-nano robot pellets with 1mg of FI TC in DMSO for 2 hours to obtain FI TC fluorescence-labeled drugs, after the drugs are orally taken with the same dosage of 10mg, euthanizing the mice for 2 hours, taking out frozen sections of intestinal tracts, and observing the interception amount of the yeast micro-nano robot in the intestinal tracts. FIG. 4 is (1) unmodified trace element-loaded yeast microcapsules, showing little fluorescence observed, indicating that very small amounts of trace element-loaded yeast microcapsules are trapped in the intestinal tract; FIG. 2 shows that the yeast micro-nano robot carrying trace elements is single, and obvious fluorescence can be seen, which indicates that the yeast micro-nano robot autonomously moves to intestinal epithelium by using glucose in intestinal tracts, and the absorption of the trace elements is increased; FIG. 3 shows that the yeast micro-nano robot sugar pill has very strong fluorescence.
Fig. 5 is a data statistical chart of the administration of yeast cells, a single trace element-loaded yeast micro-nano robot and a trace element-loaded yeast micro-nano robot pellet, and it can be seen from the results that the number of trace element-loaded yeast micro-nano robot pellets reaching the intestinal tract is significantly increased compared to unmodified yeast cells and a single yeast micro-nano robot. The cluster effect of the robot is utilized by the sugar pill, and the administration efficiency is greatly increased.
FIG. 6 is a HE diagram of the safety of the yeast micro-nano robot dragee to intestinal tracts after oral administration. Wherein, fig. 6(1) is a yeast cell, fig. 6(2) is a single yeast micro-nano robot, and fig. 6(3) is a yeast micro-nano robot dragee. The intestinal health status in fig. 6(3) is equivalent to fig. 6(1) and fig. 6(2), which illustrates that the yeast micro-nano robot dragee loaded with trace elements provided by this embodiment is safe and non-toxic, and does not harm the body.
The yeast micro-nano robot sugar pill loaded with trace elements provided by the invention takes edible fungus yeast cells as a carrier, is green and safe, and can be widely eaten and used as medicines; the yeast micro-nano robot can actively move, so that the intestinal barrier is broken through, and the drug delivery is more efficient; moreover, the yeast micro-nano robot pill aggregates one or more yeast micro-nano robots together, the pill in the intestinal tract is degraded, and the yeast micro-nano robot cluster moves, so that the drug delivery efficiency is further improved.
Therefore, the yeast micro-nano robot sugar pill loaded with the trace elements can be used for preparing medicines for treating diseases caused by trace element deficiency, but is not limited to being prepared into the sugar pill, and can also be prepared into other forms of medicinal preparations such as granules, tablets and the like, so that the yeast micro-nano robot sugar pill is convenient to take orally.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (10)
1. The yeast micro-nano robot dragee loaded with trace elements is characterized by comprising an external polysaccharide capsid and at least one internal yeast micro-nano robot, wherein the yeast micro-nano robot is composed of yeast cells, biological enzymes partially covered on the yeast cells and trace elements loaded in the yeast cells.
2. The yeast micro-nano robot dragee loaded with trace elements according to claim 1, characterized in that the components of the polysaccharide capsid are one or more of lactose, maltose, sucrose, dextrin, starch, fructose, xylose or microcrystalline cellulose.
3. The yeast micro-nano robot dragee loaded with trace elements according to claim 1, characterized in that the biological enzymes are glucose oxidase and catalase.
4. The yeast micro-nano robot dragee loaded with trace elements according to claim 1, characterized in that the trace elements are one or more of calcium, iron, zinc, selenium, copper, molybdenum, chromium, cobalt, iodine, fluorine and manganese.
5. A preparation method of the yeast micro-nano robot dragee loaded with trace elements according to any one of claims 1 to 4, which is characterized by comprising the following steps:
(1) recovering the yeast cells to enable the yeast cells to have respiration and generate carbon dioxide inside the cells;
(2) mixing the yeast cells recovered in the step (1) with a trace element salt solution, incubating, and carrying out biomineralization to obtain trace element-loaded yeast cells;
(3) mixing the yeast cells carrying the trace elements with a masking agent, drying, and removing the redundant masking agent to obtain partially masked yeast cells;
(4) adding an activating agent into the partially masked yeast cells obtained in the step (3) for activation, and removing unreacted activating agent after activation to obtain partially activated yeast cells;
(5) adding glucose oxidase and catalase into the partially activated yeast cells obtained in the step (4) for reaction, and removing unbound enzyme after reaction to obtain the trace element-loaded yeast micro-nano robot;
(6) and (4) mixing polysaccharide with the yeast micro-nano robot loaded with the trace elements in the step (5), and then preparing into a sugar pill to obtain the yeast micro-nano robot loaded with the trace elements.
6. The preparation method of the trace element-loaded yeast micro-nano robot dragee according to claim 5, characterized in that in the step (3), the mass ratio of the trace element-loaded yeast cells to the masking agent is 1 (0.01-0.25).
7. The preparation method of the trace element-loaded yeast micro-nano robot dragee according to claim 5, characterized in that in the step (4), the mass ratio of the partially masked yeast cells to the activating agent is 1 (40-80).
8. The preparation method of the yeast micro-nano robot dragee loaded with trace elements according to claim 5, characterized in that in the step (5), the mass ratio of catalase to glucose oxidase is 1 (2-5).
9. The preparation method of the trace element-loaded yeast micro-nano robot dragee according to claim 5, characterized in that in step (6), the mass ratio of the yeast micro-nano robot to the polysaccharide is 1 (50-200).
10. The preparation method of the yeast micro-nano robot dragee loaded with trace elements according to claim 5, characterized in that in the step (5), the reaction temperature is 4-25 ℃, and the reaction time is 16-24 hours.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111493812.0A CN114404386B (en) | 2021-12-08 | 2021-12-08 | Microelement-loaded yeast micro-nano robot sugar pill |
| PCT/CN2022/137373 WO2023104126A1 (en) | 2021-12-08 | 2022-12-07 | Yeast micro/nanorobot polysaccharide pill loaded with trace elements and preparation method therefor |
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| CN202111493812.0A CN114404386B (en) | 2021-12-08 | 2021-12-08 | Microelement-loaded yeast micro-nano robot sugar pill |
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| CN114404386B CN114404386B (en) | 2023-06-27 |
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Cited By (1)
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| WO2023104126A1 (en) * | 2021-12-08 | 2023-06-15 | 深圳先进技术研究院 | Yeast micro/nanorobot polysaccharide pill loaded with trace elements and preparation method therefor |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1081075A (en) * | 1993-01-01 | 1994-01-26 | 杭州民生药厂 | Se-yeast sweet pill as one health nutrient food |
| US10190100B1 (en) * | 2015-12-28 | 2019-01-29 | Verily Life Sciences Llc | Chemical modification of glucose oxidase and its application to biosensors |
| CN110182750A (en) * | 2019-05-14 | 2019-08-30 | 武汉理工大学 | A kind of urase driving can-like micro-nano motor and preparation method thereof |
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|---|---|---|---|---|
| EP3663257A1 (en) * | 2018-12-05 | 2020-06-10 | Fundació Institut de Bioenginyeria de Catalunya (IBEC) | Functionalized enzyme-powered nanomotors |
| CN114404386B (en) * | 2021-12-08 | 2023-06-27 | 深圳先进技术研究院 | Microelement-loaded yeast micro-nano robot sugar pill |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1081075A (en) * | 1993-01-01 | 1994-01-26 | 杭州民生药厂 | Se-yeast sweet pill as one health nutrient food |
| US10190100B1 (en) * | 2015-12-28 | 2019-01-29 | Verily Life Sciences Llc | Chemical modification of glucose oxidase and its application to biosensors |
| CN110182750A (en) * | 2019-05-14 | 2019-08-30 | 武汉理工大学 | A kind of urase driving can-like micro-nano motor and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| ZHANG, JT 等，: "Self-propelling micro-/nano-motors: Mechanisms, applications, and challenges in drug delivery", 《INTERNATIONAL JOURNALOFPHARMACEUTICS》 * |
| 周昶 等，: "酶驱动瓶状纳米马达的趋化行为研究", 《中国化学会第十七届全国胶体与界面化学学术会议论文（摘要）集（第二卷）》 * |
| 王唯 等，: "新型纳米酶马达的制备及其抗菌性能研究", 《分析化学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023104126A1 (en) * | 2021-12-08 | 2023-06-15 | 深圳先进技术研究院 | Yeast micro/nanorobot polysaccharide pill loaded with trace elements and preparation method therefor |
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| CN114404386B (en) | 2023-06-27 |
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