阅读说明：本技术 一种荧光素纳米微球洗手液及其制备方法 (Fluorescein nanoparticle hand sanitizer and preparation method thereof ) 是由 江千里 干宁 姚巧睿 陈全凤 江俪川 颜丹虹 李宇轩 黄淇轩 方僖 王正源 张淋 于 2019-11-29 设计创作，主要内容包括：本发明公开了一种荧光素纳米微球洗手液及其制备方法,所述荧光素纳米微球洗手液包括荧光素纳米微球和药学上可接受的载体或助剂,具体包括如下重量百分比的成分：荧光素纳米微球2-10％,富脂剂0.5-3.2％,润肤保湿剂65-90％,黏度调节剂1-4％。本发明所提供的荧光素纳米微球洗手液所采用的荧光素纳米微球的尺寸大小与细菌或病毒的大小一致,可更好地模仿病原体；其所采用的荧光素纳米微球与单一荧光素相比,荧光强度更强,且敏感度更高；所制得的荧光素纳米微球洗手液在特定波长灯源下检测,根据手中荧光亮度分布判断手消毒效果,提供一种可靠的广为医疗行业采纳的效果检测标准。(The invention discloses a fluorescein nanoparticle hand sanitizer and a preparation method thereof, wherein the fluorescein nanoparticle hand sanitizer comprises fluorescein nanoparticles and a pharmaceutically acceptable carrier or auxiliary agent, and specifically comprises the following components in percentage by weight: 2-10% of fluorescein nano-microspheres, 0.5-3.2% of fat-enriching agent, 65-90% of skin moisturizing agent and 1-4% of viscosity regulator. The dimension of the fluorescein nanospheres adopted by the fluorescein nanosphere hand sanitizer provided by the invention is consistent with that of bacteria or viruses, so that pathogens can be better simulated; compared with single fluorescein, the adopted fluorescein nanospheres have stronger fluorescence intensity and higher sensitivity; the prepared fluorescein nanoparticle hand sanitizer is detected under a light source with a specific wavelength, and the hand disinfection effect is judged according to the fluorescence brightness distribution in hands, so that a reliable effect detection standard widely adopted by the medical industry is provided.)

1. A fluorescein nanoparticle hand sanitizer is characterized by comprising fluorescein nanoparticles and a pharmaceutically acceptable carrier or auxiliary agent.

2. The fluorescein nanoparticle hand sanitizer according to claim 1, comprising the following components in percentage by weight:

3. the fluorescein nanosphere hand sanitizer according to claim 1 or 2, wherein the fluorescein nanosphere consists of fluorescein and nanospheres with a surface comprising a plurality of binding sites, and the diameter of the fluorescein nanosphere is 5nm to 1000 μm.

4. The fluorescein nanosphere hand sanitizer according to claim 3,

the fluorescein is one of fluorescein isothiocyanate and quantum dots;

and/or the nano microsphere is composed of a nano core and a shell with a plurality of binding sites on the surface, wherein the nano core is SiO₂Or Fe₃O₄@SiO₂The shell comprises amino and colloidal gold.

5. The fluorescein nanoparticle hand sanitizer according to claim 3 or 4, wherein the mass ratio of the fluorescein to the nanoparticle is 1: 8-15.

6. The fluorescein nanoparticle hand sanitizer according to claim 2, further comprising a preservative and essence, wherein the preservative and the essence are respectively contained in an amount of 0.1 to 0.2% and 0.1 to 0.2% by weight.

7. The fluorescein nanosphere hand sanitizer according to claim 2 or 6,

the fat-enriching agent is one or more of glycerate, glyceryl cocoate, isopropyl myristate, glyceryl cocoyl polyethylene glycol ester, octyl hydroxystearate, polyquaternium-7, glycerol and panthenol;

and/or the skin moistening agent is one or more of liquid paraffin, glycerol, propylene glycol, sorbitol, polyethylene glycol, butanediol, xylitol, ethanol, isopropanol, glycerol and alkyl glycoside;

and/or the viscosity regulator is NaCl and NH₄One or more of Cl and KCl.

8. The fluorescein nanoparticle hand sanitizer according to claim 6, wherein the preservative is one or more of sodium benzoate, carbolic acid, DL606, methylchloroisothiazolinone, parabens, and Ketone.

9. A method of preparing a fluorescein nanosphere hand sanitizer according to any one of claims 1 to 8 comprising:

weighing fluorescein nanospheres, fat-rich agent, skin moistening agent, viscosity regulator, antiseptic and essence according to a certain proportion; adding the fluorescein nanospheres into a skin moistening agent, then adding the fat-rich agent and the viscosity regulator while stirring, placing the mixture into a grinding machine for grinding after stirring uniformly, finally adding the preservative and the essence, and mixing uniformly to obtain the fluorescein nanospheres hand sanitizer.

10. The method for preparing a fluorescein nanosphere hand sanitizer according to claim 9 wherein the time for milling is greater than 12 hours.

Technical Field

The invention relates to the technical field of medical and health effect detection, and particularly relates to a fluorescein nanoparticle hand sanitizer and a preparation method thereof.

Background

The disease is known from the mouth, and the medium of the disease is the hand. A large body of data shows that maintaining hand hygiene is the most basic, simplest and effective means to effectively prevent, control pathogen transmission, and reduce the incidence of nosocomial infections.

Hospital infection is a considerable important link in the field of medical care and health, and now becomes a serious social problem. More than 90% of medical work is done by the hands of medical personnel during routine medical treatment and nursing activities.

Hand washing and disinfection is one of the most important measures to prevent nosocomial infections. Medical staff are reported to have gram-negative bacillus carrying rate of 20-30%, staphylococcus aureus separated from 25-68% of ordinary ward soil protection hands, and burn ward or ward staff can reach 80% or more. In clinical care, the hands of the nursing staff can obtain 16cfu/cm per minute²The bacterium of (1); the medical staff can increase the bacteria on the hands by 100 cfu/cm through simple operations (such as lifting the patient from the bed, measuring the blood pressure or the pulse, contacting the hands of the patient, turning the patient, contacting the clothes or the bed sheet of the patient, contacting the bedside table, the mattress, the infusion pump and the like)²The bacterium of (1). Because gram-negative bacilli are rarely transmitted in the air, most of the hospital infection caused by the gram-negative bacilli is transmitted to patients through hands of medical staff, and the hospital infection events caused by the gram-negative bacilli are rare.

Research shows that medical staff insist on high-quality hand washing disinfection every day can reduce the incidence rate of nosocomial infection by 25-50%; when the hand washing rate is increased from 48% to 60%, the nosocomial infection is correspondingly reduced from 16.9% to 9.9%, and therefore, hand hygiene is the simplest, most effective and most economical method for reducing nosocomial infection.

In addition to a simple and effective role in nosocomial infections, it is also of particular interest to enhance hand hygiene in certain populations. Bacterial load on the hands of medical personnel 10⁸cfu/cm²Generally non-pathogenic, but immunocompromised patients 10³cfu/cm²Even less may be pathogenic. The hand hygiene can prevent children's skin infection, eye infection, intestinal parasitic disease, SARS and avian influenza. The main causes of death in children under five years old are pneumonia and diarrhea, more than 350 million children leave the world every year due to the two diseases, and the children can be saved by daily hand cleaningThe lives of some children.

Hand hygiene has clear requirements in various guidelines and review standards: in 2007, final draft was issued by WHO consulting specialist groups, WHO consultant committees, and manual hygiene program drafts, WHO medical institution manual hygiene guidelines, which were co-written by the WHO consultant groups, WHO consulted council, and manual hygiene program drafts, and which were divided into 5 sections, including review of data regarding manual hygiene science, recommended terms, and evaluation of results. Since 12 months and 1 days in 2009, the national ministry of health has enacted "medical staff hand hygiene norms", and has specifically stipulated the management and basic requirements of medical staff hand hygiene, hand hygiene facilities, hand washing and hygiene hand disinfection, surgical hand disinfection, monitoring of hand hygiene effects, and the like. The ' standard for evaluating the three-level comprehensive hospital ' also clearly requires that the disinfection of objects, the surface of the object, the sampling inspection of hands and air on site meet the specified requirements '. Meanwhile, each hospital also sets up relevant standards for washing hands, and requires that medical personnel must be trained in hand washing skills before going on duty.

Meanwhile, not only in the medical industry, hand hygiene also relates to a plurality of industries related to daily life hygiene of people, such as the infant industry, the catering industry, the food industry, the tourism industry and the like. In the investigation of the hand hygiene condition of a food worker, the average total number of bacteria and the number of coliform positive bacteria of the food worker after washing hands are obviously reduced compared with the number of the coliform positive bacteria of the food worker before washing the hands, and the number of the coliform positive bacteria of the food worker is also obviously reduced. Therefore, the hand hygiene can greatly reduce the potential safety hazard of food from the source.

Hand hygiene includes running water disinfection, surgical hand disinfection, and sanitary hand disinfection, wherein the method of disinfecting hands may be used when it is not convenient for medical personnel to wash hands with running water between procedures, or between contacts with two different patients.

The traditional detection method is to carry out microorganism sampling detection after washing hands, but the method has long time and is complex and inconvenient to use in daily life. Therefore, it is important to explore a reliable method for detecting effects and related criteria.

Zhanyun et al disclose a testing device for hand washing skills of medical staff (patent publication No. CN209102605U), which comprises a fluorescent agent spraying part (an ultrasonic atomizer-spraying fluorescent agent aerosol towards the hands of the staff) and a detection part (a dark box-provided with an ultraviolet lamp and a camera device), and the use method comprises that before washing hands ①, the staff enters the fluorescent agent spraying part with the hands, ② confirms that the hands are stained with fluorescent light and take a picture ③ to wash the hands for a certain specified time under the irradiation of the ultraviolet lamp, and ④ observes whether the hands of the staff have blue light and the intensity and distribution of the blue light under the irradiation of the ultraviolet lamp.

A hand washing detector (CN 203881683U) for relaxing the uterus is composed of a casing with a slot on its top for connecting it to computer and symmetrical holes on both sides of its bottom, an ultraviolet fluorescent lamp and a camera in said casing, ① and its application method, ② for washing hands, ③ for displaying the photos of both hands, and ④ for judging the effect of washing hands.

The German Bonn university application discloses a combined transport container and lighting device (patent publication No.: DE202006011931U1) comprising an outer container and a lamp holder; the outer container comprises non-reflective side walls (the walls of the outer transport container are matt black to avoid unnecessary reflection of light) with an opening for insertion of a hand, in order to avoid eye damage, the viewing aperture at the top of the outer transport container is covered with acrylic glass, and the lamp holder has a light source arranged on the inside of the cover. The combined device is used for demonstrating and quantifying the effectiveness of reducing the test dirt of the fluorescent marker, particularly for hand washing, and especially for training in places such as day-care centers and schools.

How to simply, conveniently and effectively detect the hand washing effect in the field is a key technical problem which needs to be solved urgently by technical personnel in the field.

Disclosure of Invention

Aiming at the defects in the prior art, the invention provides a fluorescein nanoparticle hand sanitizer and a preparation method thereof.

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

a fluorescein nanoparticle hand sanitizer is characterized by comprising fluorescein nanoparticles and a pharmaceutically acceptable carrier or auxiliary agent.

In detail, fluorescein is a synthetic organic compound that emits green fluorescence under blue or ultraviolet irradiation.

In the current research field, Fluorescein Isothiocyanate (FITC), Phycoerythrin (PE), etc. are commonly used as fluorescein, mainly for:

1) a redox indicator that forms a luciferin-adenosine complex with ATP, which is then conjugated to luciferase; in the oxidation-reduction process, the activated fluorescein emits light and can be used for detecting living substances and quantitatively analyzing trace substances; such as fluorometric measurements.

2) A fluorescent adsorption indicator.

3) An acid-base titration indicator; for titration of chlorine, bromine, iodine.

4) Important pigments for antifreeze; the antifreezing solution can show green fluorescence.

5) And others: chemical analysis indicators, biological stains, cosmetic stains, and the like.

Compared with fluorescein, the size of the fluorescein nanospheres is consistent with that of bacteria or viruses, so that the fluorescein nanospheres can better simulate pathogens; the fluorescein nanospheres have stronger fluorescence intensity and higher sensitivity; the fluorescein is easy to quench after being exposed in the air for a long time, the shelf life is about 1 year, and the fluorescein nano microsphere has longer shelf life, is more stable and is more convenient in the processes of production, storage, transportation and application.

In the technical scheme, the fluorescein nanoparticle hand sanitizer comprises the following components in percentage by weight:

the fluorescein nanospheres are mutually soluble with other raw material components in the hand sanitizer formula under a certain condition, the hand sanitizer prepared by mixing the components can be detected under a light source with a specific wavelength, and the hand disinfection effect is judged according to the fluorescence brightness distribution in hands, so that a reliable effect detection standard widely adopted in the medical industry is provided, and the method can be expanded to the food industry, kindergartens, epidemic areas and the like.

Specifically, in the above technical solution, the fluorescein nanospheres are composed of fluorescein and nanospheres having a surface comprising a plurality of binding sites, and the diameter of the fluorescein nanospheres is 5nm to 1000 μm.

In detail, in the above technical solution, the fluorescein is one of fluorescein isothiocyanate and quantum dots.

In detail, in the above technical solution, the nanoparticle is composed of a nano-core and a shell with a surface comprising a plurality of binding sites, the nano-core is SiO₂Or Fe₃O₄@SiO₂Said shell comprising amino (-NH)₃) And colloidal gold.

Preferably, in the technical scheme, the mass ratio of the fluorescein to the nano-microspheres is 1: 8-15.

Further, in the technical scheme, the fluorescein nanoparticle hand sanitizer further comprises a preservative and essence, wherein the preservative and the essence are respectively 0.1-0.2% and 0.1-0.2% in weight percentage.

In detail, in the above technical solution, the superfatting agent is one or more of glycerate, glyceryl cocoate, isopropyl myristate, glyceryl cocoyl polyethylene glycol ester, octyl hydroxystearate, polyquaternium-7, glycerin and panthenol.

In detail, in the above technical scheme, the skin-moistening agent is one or more of liquid paraffin, glycerin, propylene glycol, sorbitol, polyethylene glycol, butylene glycol, xylitol, ethanol, isopropanol, glycerol and alkyl glycoside.

In detail, in the above technical scheme, the viscosity regulator is NaCl or NH₄One or more of Cl and KCl.

In detail, in the above technical solution, the preservative is one or more of sodium benzoate, carbolic acid, DL606, methylchloroisothiazolinone, parabens, and kathon.

The invention also provides a preparation method of the fluorescein nanoparticle hand sanitizer, which comprises the following steps:

weighing fluorescein nanospheres, fat-rich agent, skin moistening agent, viscosity regulator, antiseptic and essence according to a certain proportion; adding the fluorescein nanospheres into a skin moistening agent, then adding the fat-rich agent and the viscosity regulator while stirring, placing the mixture into a grinding machine for grinding after stirring uniformly, finally adding the preservative and the essence, and mixing uniformly to obtain the fluorescein nanospheres hand sanitizer.

Specifically, in the above technical solution, the grinding time is greater than 12 h.

The principle adopted by the fluorescein nanoparticle hand sanitizer provided by the application is as follows: the method is characterized in that fluorescein nanospheres are dissolved in liquid consisting of fat-rich agent, skin moisturizing agent, viscosity regulator, preservative, essence and the like, can show fluorescence under a light source with specific wavelength, and comprises the following steps: 1) taking 3-4ml of fluorescein nanoparticle hand sanitizer in hands; 2) performing rapid hand disinfection according to the hand washing standard of disinfection technology; 3) placing both hands under a light source with a specific wavelength for irradiation, judging the disinfection effect of the hands according to the fluorescence brightness distribution in the hands, if the hands are not thoroughly cleaned, the fluorescein nanospheres are unevenly distributed on the hands, and certain parts of the hands are rarely or even lacked; if the fluorescein nanospheres are uniformly distributed on the hands, the rapid hand disinfection operation is standard, and the hand disinfection is thorough; 4) cleaning both hands by using matched hand washing liquid under running water; 5) placing the hands under a light source with a characteristic wavelength for irradiation again, and if residual fluorescence appears, proving that the hand washing operation is not standard and the hands are not washed; if no fluorescence residue is observed, the washing operation is standard, and the hand is washed.

The invention has the advantages that:

(1) the size of the fluorescein nanospheres adopted by the fluorescein nanosphere hand sanitizer provided by the invention is 5nm-1000 mu m, is consistent with the size of bacteria or viruses, and can better simulate pathogens;

(2) compared with single fluorescein, the fluorescein nanospheres adopted by the fluorescein nanosphere hand sanitizer provided by the invention have stronger fluorescence intensity and higher sensitivity;

(3) the fluorescein nanospheres adopted by the fluorescein nanosphere hand sanitizer provided by the invention are mutually soluble with other raw material components in a content formula under a certain condition, the hand sanitizer prepared by mixing the components can be detected under a lamp source with a specific wavelength, the hand disinfection effect is judged according to the fluorescence brightness distribution in hands, a reliable effect detection standard widely adopted in the medical industry is provided, and the fluorescein nanosphere hand sanitizer can be expanded to the food industry, kindergartens, epidemic areas and the like.

Drawings

FIG. 1 is a schematic diagram illustrating a method of using a fluorescein nanoparticle hand sanitizer in an embodiment of the present invention;

FIG. 2 is a comparison graph of the fluorescence effect of the fluorescein isothiocyanate nanoparticle hand sanitizer prepared in example 2 of the present invention and the fluorescein isothiocyanate nanoparticle hand sanitizer prepared in comparative example 1 with the same concentration under the irradiation of a light source with a specific wavelength;

FIG. 3 is a comparison chart of fluorescence changes of the fluorescein isothiocyanate nanoparticle hand sanitizer prepared in example 2 of the present invention and the fluorescein isothiocyanate hand sanitizer prepared in comparative example 1 with equal concentration before and after 1 hour irradiation in sunlight.

Detailed Description

The following detailed description of embodiments of the present invention is provided in connection with the accompanying drawings and examples.

The following examples are intended to illustrate the present invention, but not to limit the scope of the invention, which is defined by the claims.

Unless otherwise specified, the test reagents and materials used in the examples of the present invention are commercially available.

Unless otherwise specified, the technical means used in the examples of the present invention are conventional means well known to those skilled in the art.