CN114470228B - Blood coagulation medicine-carrying yeast immune micro-nano biological robot and preparation and application thereof - Google Patents
Blood coagulation medicine-carrying yeast immune micro-nano biological robot and preparation and application thereof Download PDFInfo
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- 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
- A61K47/52—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 an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
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- 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
- A61K47/6921—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6925—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a microcapsule, nanocapsule, microbubble or nanobubble
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- 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
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- A—HUMAN NECESSITIES
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- 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
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention provides a blood coagulation medicine-carrying yeast immune micro-nano biological robot and a preparation method and application thereof. The blood coagulation medicine-carrying yeast immune micro-nano biological robot comprises a yeast microcapsule, blood coagulation medicine-carrying nanoparticles embedded in the yeast microcapsule, and carbonate crystals growing on the half side of the yeast microcapsule. The blood coagulation medicine-carrying yeast immune micro-nano biological robot provided by the invention can rapidly stop blood in a deep wound, and can rapidly repair tissues based on the yeast microcapsule autoimmune effect.
Description
Technical Field
The invention belongs to the technical field of hemostatic drugs, and particularly relates to a blood coagulation drug-loaded yeast immune micro-nano biological robot and a preparation method and application thereof.
Background
Excessive blood loss is a major cause of more than 50% of battlefield deaths, 20% of hospital patient deaths, and 30% of traumatic deaths. The hemostatic products such as fibrin glue, gelatin sponge, chitosan hemostatic powder and the like which are commonly used clinically at present have better hemostatic effect on superficial wounds, but have limited control effect on severe internal organs such as irregular wounds or penetrating wounds such as stomach, aortic/venous rupture and the like. Because it does not have the function of actively moving and orienting deep tissue bleeding areas, it is difficult to quickly and efficiently stop bleeding. It is also a great challenge how to prevent infection of the wound and promote rapid healing of the wound after hemostasis.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a blood coagulation medicine-carrying yeast immune micro-nano biological robot for rapidly stopping and repairing wounds, and a preparation method and application thereof.
The method is realized by the following technical scheme:
a blood coagulation medicine-carrying yeast immune micro-nano biological robot comprises a yeast microcapsule, blood coagulation medicine-carrying nano particles embedded in the yeast microcapsule, and carbonate crystals with half sides growing in the yeast microcapsule.
Further, the yeast microcapsule is derived from edible yeast cells, the components of the yeast microcapsule are beta- (1, 3) -D-glucan, and the edible yeast cells are Saccharomyces cerevisiae, hansenula polymorpha, issatchenkia orientalis, pichia pastoris, meilin meldonium, rhodosporidium or candida.
Further, the nanoparticle of the coagulation drug-loaded nanoparticle is a charged lipid polymer nanoparticle, a liposome, a polymer nanoparticle or an albumin nanoparticle.
Further, the coagulation medicament in the nanoparticle carrying the coagulation medicament is one or more of carbomer, troxerutin, pituitary posterior lobe extract, vitamin C, glucocorticoid, phenol sulfoethylamine, vitamin K, thrombin, batroxobin, hemophilia globulin, protamine and gel sponge.
Further, the carbonate crystals are in a flower shape, and the carbonate crystal components are one or more of calcium carbonate, magnesium carbonate and zinc carbonate.
The invention also provides a preparation method of the yeast immune micro-nano biological robot, which comprises the following steps:
(1) Incubating the nanoparticle carrying the blood coagulation medicine with the yeast microcapsule at constant temperature, and centrifuging and precipitating to obtain the yeast microcapsule carrying the blood coagulation medicine; the duration of the constant temperature co-incubation is preferably 0.5-24 hours;
(2) Dissolving the yeast microcapsule carrying the blood coagulation medicine, a surfactant and a metal salt into an ethanol water solution, and then stirring; wherein the metal salt is one or more of calcium salt, magnesium salt or zinc salt; preferably for 0.5 to 1 hour;
(3) Slowly dripping the soluble carbonate ethanol water solution into the step (2), stirring at room temperature, and standing to obtain a yeast immune micro-nano biological robot precursor; preferably, the mixture is stirred vigorously at room temperature for 1 to 3 hours and then kept stand for 24 to 48 hours;
(4) Washing, centrifuging and purifying the yeast immune microbial nano-robot precursor prepared in the step (3), and drying, wherein the drying is preferably performed at 50-60 ℃ for 48-72 hours in vacuum, so as to obtain the blood coagulation medicine-carrying yeast immune microbial nano-robot.
Further, the surfactant in the step (2) is a cationic surfactant, and the cationic surfactant is adsorbed on the surface of the negatively charged yeast microcapsule carrying the coagulation medicament. Yeast microcapsule carrying coagulation medicine: cationic surfactant: the mass ratio of the ethanol is 1: (0.05-0.5): (50-100).
The cationic surfactant is preferably one or more of alkyl trimethyl ammonium bromide, alkyl trimethyl ammonium chloride, alkyl benzyl dimethyl ammonium chloride, dialkyl dimethyl ammonium chloride and alkyl pyridine chloride.
Preferably, in step (3), a soluble carbonate ethanol aqueous solution is added dropwise: the molar ratio of the metal salt is 1:1, so that the carbonate ions and the metal ions can be completely reacted.
The blood coagulation medicine-carrying yeast immune micro-nano biological robot provided by the invention can be applied to preparing hemostatic therapeutic medicines. In particular, the blood coagulation medicine-carrying yeast immune micro-nano biological robot is used for preparing hemostatic and immune infection medicines.
Specifically, the coagulant-carrying yeast immune micro-nano biological robot can be mixed with protonic acid salt for rapid hemostasis and repair of deep, penetrating and irregular wounds with broken aorta or vein.
Further, the mass ratio of the coagulant-carrying yeast immune micro-nano biological robot to the protonic acid is 1 (1-100).
The blood coagulation medicine carrying yeast immune micro-nano biological robot can be used for preparing oral hemostatic, and can be prepared into capsules, tablets, oral liquid and other dosage forms for direct oral administration.
Compared with the prior art, the invention has the following advantages:
1. the blood coagulation medicine-carrying yeast immune micro-nano biological robot is prepared by taking the yeast cell wall as a carrier, the material sources are economical and wide, and the edible yeast is used as the raw material, so that the blood coagulation medicine-carrying yeast immune micro-nano biological robot is safe and nontoxic and has good biocompatibility.
2. The yeast microcapsule has the functions of activating macrophage immunity, preventing wound infection and promoting wound healing while stopping bleeding quickly, and has multifunction.
3. The flower-like carbonate crystals are uniaxially grown on the surface of the yeast microcapsule by the gel-sol principle, no special equipment is needed, the preparation process is simple, mass production can be realized, and the method is suitable for large-scale preparation.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are needed in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of a preparation of a coagulant-loaded yeast immune micro-nano biological robot;
FIG. 2 is a fluorescence imaging diagram of a blood clotting drug-loaded yeast microcapsule and blood clotting drug-loaded yeast immunomicrobial robot;
FIG. 3 is a graph of stomach tissue of a healthy group and a comparison of effects of immunization of a micronano-biological robot with a coagulant-loaded yeast and treatment of gastric bleeding in mice with a non-robotic group provided by the present invention.
Detailed Description
The following description is of the preferred embodiments of the present invention, and it should be noted that it will be apparent to those skilled in the art that modifications and variations can be made without departing from the principle of the invention, and these modifications and variations are also regarded as the scope of the invention.
The invention provides a blood coagulation medicine-carrying yeast immune micro-nano biological robot, which structurally comprises a yeast microcapsule, blood coagulation medicine-carrying nanoparticles embedded in the yeast microcapsule, and carbonate crystals growing on the yeast microcapsule at half sides, wherein the carbonate crystals comprise one or more of calcium carbonate, magnesium carbonate and zinc carbonate.
The provided coagulant-carrying yeast immune micro-nano biological robot grows flower-like carbonate crystals on the surface of a yeast microcapsule in a single axis manner by a gel-sol principle: firstly, the added cationic surfactant is adsorbed on the surface of the anionic yeast microcapsule to form a gel state similar to micelle, after the ethanol aqueous solution of soluble carbonate is dripped, the cationic surfactant on the surface of the yeast microcapsule is dissolved by ethanol molecules in liquid drops, meanwhile, carbonate ions in the liquid drops immediately react with metal ions at the point to generate insoluble carbonate crystal nuclei, and after standing, the carbonate gradually grows into flower-shaped carbonate crystals at the crystal nuclei. The salt decomposition carbonate crystallization automatically advances into deep tissues of a bleeding wound by generating carbon dioxide gas at a bleeding focus, and then achieves the aim of hemostasis by releasing a coagulant. And the yeast microcapsule has the function of activating macrophage immunity, and can prevent wound infection and promote wound healing while stopping bleeding rapidly.
The invention also provides a preparation method of the blood coagulation medicine-carrying yeast immune micro-nano biological robot, which comprises the steps of incubating the blood coagulation medicine-carrying nanoparticle and the yeast microcapsule at constant temperature, and then centrifuging and precipitating to obtain the blood coagulation medicine-carrying yeast microcapsule; dissolving the yeast microcapsule carrying the blood coagulation medicament, a surfactant, and calcium salt or magnesium salt or zinc salt into ethanol water solution, and then stirring; slowly adding sodium carbonate solution, stirring at room temperature, and standing to obtain a yeast immune micro-nano biological robot precursor; and finally, washing, centrifuging and purifying the prepared precursor of the yeast immune microbial nano-robot, and drying to obtain the yeast immune microbial nano-robot.
Cationic surfactants include, but are not limited to, one or more of alkyl trimethyl ammonium bromide, alkyl trimethyl ammonium chloride, alkyl benzyl dimethyl ammonium chloride, dialkyl dimethyl ammonium chloride, and alkyl pyridine chloride.
The yeast microcapsule is derived from the cell wall of an edible yeast cell, and the component of the yeast microcapsule is beta- (1, 3) -D-glucan, and in some specific embodiments, the yeast cell can be selected from one or more of Saccharomyces cerevisiae, hansenula polymorpha in grape juice, hansenula polymorpha in season, issatchenkia orientalis, kluyveromyces pichia pastoris, pichia mozus, mei-polar Mei-ji yeast, rhodosporidium and Candida.
In some specific embodiments, the nanoparticle is one or more of a charged lipid polymer nanoparticle, a liposome, a polymer nanoparticle, and an albumin nanoparticle, the nanoparticle being for loading a clotting drug. The clotting drug may be selected from one or more of carboplatin, troxerutin, pituitary posterior lobe extract, vitamin C, glucocorticoid, phenolsulfonic ethylamine, vitamin K, thrombin, batroxobin, antihemophilic globulin, protamine, and gel sponge.
The blood coagulation medicine-carrying yeast immune micro-nano biological robot provided by the invention can be applied to preparation of hemostatic therapeutic medicines. In particular, the blood coagulation medicine-carrying yeast immune micro-nano biological robot is used for preparing hemostatic and immune infection medicines. The yeast immune microbial robot carrying the coagulant can be mixed with protonic acid salt for rapid hemostasis and repair of deep, penetrating and irregular wounds such as aortic/venous rupture, and the mass ratio of the yeast immune microbial robot to the protonic acid is 1 (1-100). The blood coagulation medicine-carrying yeast immune micro-nano biological robot provided by the invention can also be directly orally taken, and is suitable for rapid treatment and repair of gastrorrhagia.
The advantageous effects of the present invention are further described below with reference to specific examples.
Example 1
(1) Uniformly mixing 1mg of thrombin-carrying nanoparticle with 10mg of yeast microcapsule, incubating for 1 hour at a constant temperature of 37 ℃, centrifuging at 5000rpm/min for 10 minutes, washing with ultrapure water for three times, and precipitating to obtain the yeast microcapsule carrying the blood coagulation medicine;
(2) The yeast microcapsule carrying the coagulation medicament prepared in the step (1), 36.4mg of cetyltrimethylammonium bromide (CTAB) and 111mg of calcium chloride (CaCl) 2 ) Adding the mixture into 50mL of 50% ethanol water solution, and vigorously stirring for 0.5-1 hour;
(3) 50mL of a 2.12mg/mL sodium carbonate/50% ethanol solution (Na 2 CO 3 ). Standing the mixed solution for 24-48 hours at room temperature to obtain a precursor of the yeast immune micro-nano biological robot;
(4) And (3) washing the yeast immune microbial robot precursor prepared in the step (3) with ammonium nitrate/ethanol for three times to remove CTAB, and then placing the product in a 50-60 ℃ oven for vacuum drying for 24-48 hours to obtain the blood coagulation medicine-carrying yeast immune microbial robot.
The preparation schematic diagram of the yeast immune micro-nano biological robot can be seen in fig. 1. In fig. 1, A is a yeast microcapsule, B is a nanoparticle carrying a blood coagulation drug, C is a yeast microcapsule embedded with the blood coagulation drug, and D is a yeast immune micro-nano biological robot provided by the invention.
Example 2
(1) Uniformly mixing 1mg of the carbazochrome-carrying nanoparticle with 5mg of the yeast microcapsule, incubating for 124 hours at the constant temperature of 37 ℃, centrifuging at 5000rpm/min for 10 minutes, washing with ultrapure water for three times, and precipitating to obtain the carbazochrome-carrying yeast microcapsule;
(2) The yeast microcapsule carrying the blood coagulation medicine prepared in the step (1), 36.4mg of Cetyl Trimethyl Ammonium Bromide (CTAB) and 111mg of calcium chloride (CaCl) 2 ) Adding the mixture into 50mL of 70% ethanol water solution, and vigorously stirring for 0.5-1 hour;
(3) 50mL of a 2.12mg/mL sodium carbonate/70% ethanol solution (Na 2 CO 3 ) Standing the mixed solution at room temperature for 24-48 hr to obtain yeastImmune micro-nano biological robot precursors;
(4) Washing the precursor of the yeast immune microbial robot prepared in the step (3) with ammonium nitrate/ethanol for three times to remove CTAB, and then placing the precursor in a 50-60 ℃ oven for vacuum drying for 24-48 hours to prepare the yeast immune microbial robot.
Referring to fig. 2, fluorescent imaging was performed on blood clotting drug-loaded yeast microcapsules and yeast immunomicrobial robots. The first row of 4 images are respectively the fluorescent imaging of the drug-carrying yeast microcapsule under the bright field, the fluorescent imaging of the drug-carrying yeast microcapsule under the calcium fluorescent white, the fluorescent imaging of the nano-particles in the drug-carrying yeast microcapsule and the combined image of the first three images, and the second row of 4 images are respectively the fluorescent imaging of the blood coagulation drug-carrying yeast immune micro-nano robot under the bright field, the fluorescent imaging of the drug-carrying yeast microcapsule under the calcium fluorescent white, the fluorescent imaging of the nano-particles in the drug-carrying yeast microcapsule and the combined image of the first three images. The yeast immune micro-nano biological robot is successfully loaded with nano particles, and the half side of the robot is provided with flower-shaped calcium carbonate crystals.
Experimental example
The yeast immune micro-nano biological robot is used for treating the bleeding of different parts in the body of the mouse, and compared with the repairing time without the yeast immune micro-nano biological robot, and the result is shown in table 1.
TABLE 1
As can be seen from Table 1, the yeast immune micro-nano biological robot provided by the invention is superior to the non-robot group in terms of hemorrhaging time and wound repair time for treating hemorrhage symptoms at different parts inside the body of a mouse.
Fig. 3 is a graph showing the effects of treating gastrorrhagia with the yeast immune microbial robot and the non-robot group (i.e., the blood coagulation medicine-carrying yeast immune microbial robot provided by the invention is not used, and the blood coagulation medicine is directly used) compared with the healthy group, and as can be seen from fig. 3, the blood coagulation medicine-carrying yeast immune microbial robot provided by the invention has a better effect of treating gastrorrhagia compared with the non-robot group compared with the healthy group.
The foregoing description of the preferred embodiments of the invention is not intended to limit the invention to the precise form disclosed, and any such modifications, equivalents, and alternatives falling within the spirit and scope of the invention are intended to be included within the scope of the invention.
Claims (9)
1. The blood coagulation medicine-carrying yeast immune micro-nano biological robot is characterized by comprising a yeast microcapsule, blood coagulation medicine-carrying nanoparticles embedded in the yeast microcapsule and carbonate crystals growing on the half side of the yeast microcapsule;
the preparation method of the coagulant-carrying yeast immune micro-nano biological robot comprises the following steps:
(1) Incubating the nanoparticle carrying the blood coagulation medicine with the yeast microcapsule at constant temperature, and centrifuging and precipitating to obtain the yeast microcapsule carrying the blood coagulation medicine;
(2) Dissolving the yeast microcapsule carrying the blood coagulation medicine, a surfactant and a metal salt into an ethanol water solution, and then stirring; wherein the metal salt is one or more of calcium salt, magnesium salt or zinc salt;
(3) Slowly dripping the soluble carbonate ethanol water solution into the step (2), stirring at room temperature, and standing to obtain a yeast immune micro-nano biological robot precursor;
(4) Washing, centrifuging and purifying the yeast immune microbial nano-robot precursor prepared in the step (3), and drying to obtain the blood coagulation medicine-carrying yeast immune microbial nano-robot.
2. The coagulants-loaded yeast immune microbial robot of claim 1, wherein the yeast microcapsule is derived from edible yeast cells, the component of the yeast microcapsule is beta- (1, 3) -D-glucan, and the edible yeast cells are saccharomyces cerevisiae, hansenula polymorpha, isaria orientalis, pichia pastoris, pichia membranaceus, pichia mermaica, rhodosporidium or candida.
3. The coagulum-loaded yeast immune microbial robot of claim 1, wherein the nanoparticle is a liposome, a polymer nanoparticle, or an albumin nanoparticle.
4. The blood coagulation drug-loaded yeast immune microbial robot of claim 1, wherein the blood coagulation drug in the blood coagulation drug-loaded nanoparticles is one or more of carbomer, troxerutin, pituitary posterior leaflet, vitamin C, glucocorticoid, phenolsulfoethylamine, vitamin K, thrombin, batroxobin, anti-hemophilia globulin, protamine or gel sponge.
5. The coagulant-loaded yeast immune micro-nano biological robot of claim 1, wherein the carbonate crystal component is one or more of calcium carbonate, magnesium carbonate and zinc carbonate.
6. The method for preparing the coagulant-carrying yeast immune micro-nano biological robot according to any one of claims 1 to 5, which is characterized by comprising the following steps:
(1) Incubating the nanoparticle carrying the blood coagulation medicine with the yeast microcapsule at constant temperature, and centrifuging and precipitating to obtain the yeast microcapsule carrying the blood coagulation medicine;
(2) Dissolving the yeast microcapsule carrying the blood coagulation medicine, a surfactant and a metal salt into an ethanol water solution, and then stirring; wherein the metal salt is one or more of calcium salt, magnesium salt or zinc salt;
(3) Slowly dripping the soluble carbonate ethanol water solution into the step (2), stirring at room temperature, and standing to obtain a yeast immune micro-nano biological robot precursor;
(4) Washing, centrifuging and purifying the yeast immune microbial nano-robot precursor prepared in the step (3), and drying to obtain the blood coagulation medicine-carrying yeast immune microbial nano-robot.
7. The method for preparing a coagulant-loaded yeast immune micro-nano biological robot according to claim 6, wherein in the step (2), the surfactant is a cationic surfactant, the cationic surfactant is adsorbed on the surface of a negatively charged coagulant-loaded yeast microcapsule, and the coagulant-loaded yeast microcapsule: cationic surfactant: the mass ratio of the ethanol is 1: (0.05-0.5): (50-100).
8. The method for preparing a coagulant-loaded yeast immune micro-nano biological robot according to claim 6, wherein in the step (3), a soluble carbonate ethanol aqueous solution is added dropwise: the molar ratio of the metal salts was 1:1.
9. Use of a coagulant loaded yeast immune micro-nano-robot according to any one of claims 1-5 or a coagulant loaded yeast immune micro-nano-robot prepared according to the preparation method of any one of claims 6-8 in the preparation of a hemostatic therapeutic drug.
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| PCT/CN2022/136899 WO2023104027A1 (en) | 2021-12-08 | 2022-12-06 | Yeast immune micro-nano biorobot loaded with blood coagulation drugs, preparation thereof and application thereof |
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| CN103120795B (en) * | 2011-10-27 | 2015-04-15 | 四川大学 | Preparation targeting macrophages |
| US10864168B2 (en) * | 2014-10-29 | 2020-12-15 | The Regents Of The University Of California | Bioactive delivery vehicles |
| CN104910292B (en) * | 2015-05-14 | 2017-06-30 | 中国农业科学院农产品加工研究所 | The method for preparing yeast β D glucans using molecule assembling solubilization technique |
| CN105168180A (en) * | 2015-09-30 | 2015-12-23 | 中国人民解放军第三军医大学 | Oral targeted carrier system based on yeast capsules and preparation method of oral targeted carrier system |
| CN107233298B (en) * | 2016-03-28 | 2021-01-22 | 复旦大学 | Yeast cell wall particle preparation for promoting oral absorption of protein polypeptide medicine |
| TWI727411B (en) * | 2019-08-29 | 2021-05-11 | 國立清華大學 | Oral drug delivery system and method for fabricating thereof |
| CN110819614B (en) * | 2019-11-13 | 2023-04-11 | 武汉理工大学 | Method for improving driving force of enzyme-driven micro-nano motor |
| CN111135339B (en) * | 2020-01-16 | 2021-03-16 | 西南大学 | Preparation method of hemostatic agent with directional propelling function based on janus structure |
| CN113616623A (en) * | 2021-09-10 | 2021-11-09 | 大连理工大学 | Microcapsule oral medicine based on yeast delivery carrier and preparation method and application thereof |
| CN114470228B (en) * | 2021-12-08 | 2023-06-27 | 深圳先进技术研究院 | Blood coagulation medicine-carrying yeast immune micro-nano biological robot and preparation and application thereof |
-
2021
- 2021-12-08 CN CN202111495913.1A patent/CN114470228B/en active Active
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2022
- 2022-12-06 WO PCT/CN2022/136899 patent/WO2023104027A1/en unknown
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| CN114470228A (en) | 2022-05-13 |
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