CN116271205B - Liquid band-aid containing black phosphorus nano sheet component and preparation method thereof - Google Patents

Abstract

The invention provides a liquid band-aid containing black phosphorus nano-sheet components and a preparation method thereof. The liquid band-aid comprises film forming substances, solvents, adhesion promoters, local anesthetics, antibacterial agents, anti-inflammatory agents, moisturizers and fragrances. The invention uses the 'nanometer knife' effect of the lamellar edge structure of the black phosphorus nanometer sheet, takes the black phosphorus nanometer sheet as an antibacterial component of the liquid band-aid, fully exerts the physical antibacterial property of the black phosphorus nanometer sheet, realizes high-efficiency antibacterial sterilization, and simultaneously reduces the damage to human bodies to the minimum due to the self degradability and high biocompatibility. The liquid band-aid prepared by the invention has the functions of stopping bleeding, resisting bacteria and diminishing inflammation, has the functions of moisturizing and protecting skin, is convenient to use, quick in film forming, small in skin irritation, and ideal in efficacy, and can effectively promote healing of wound parts.

Description

Liquid bandage containing black phosphorus nanosheets and preparation method thereof

Technical Field

The invention belongs to the field of medical devices, and in particular relates to a liquid band-aid containing black phosphorus nanosheet components and a preparation method thereof.

Background Art

Black phosphorus (BP) is an allotrope of phosphorus that is very similar to graphite in appearance, performance and structure. It is black, flaky and conductive. The linked atoms are in the form of wrinkled sheets that can be peeled off into a two-dimensional graphene-like layer structure. The two-dimensional black phosphorus has many excellent physical and chemical properties and has shown good application prospects in many fields such as microelectronics, optoelectronics, and energy catalysis. At the same time, as a nanomaterial composed of a single phosphorus element, it also has good biological activity and biocompatibility, showing great potential in the biomedical field.

Black phosphorus nanosheet (BPnanoshet) is a new type of nanomaterial obtained by processing black phosphorus. It has good biocompatibility in the body, and the products obtained by degradation in the body are mainly phosphate and water, which can be automatically discharged after metabolism and have no obvious negative impact on the human body. In 2015, Yu Xuefeng, a researcher at the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences, Zhu Jianhao, a professor at the City University of Hong Kong, and Zhang Han, a professor at Shenzhen University, successfully prepared black phosphorus quantum dots (BPQDs) using liquid phase exfoliation. They can effectively kill tumor cells under near-infrared light and have good biocompatibility, revealing that black phosphorus materials have good prospects in the field of biomedicine (Yu X F, et al. Angew. Chem. Int. Ed. 2015, 54, 11526-11530). Liu YN et al. (Liu YN, et al. Adv. Mater. 2017, 29) used the black phosphorus nanosheets with negative charges and wrinkled multilayer structures to achieve successful drug loading, with a loading amount far higher than that of traditional nano drug delivery platforms, which provides a new idea for the application of black phosphorus nanomaterials in biomedicine. Shi J J et al. (Shi J J, et al. Adv. Mater. 2017, 29) successfully developed a black phosphorus nanosheet carrier system that can load the clinical drug doxorubicin based on the easy functionalization of the black phosphorus nanosheet surface and the large specific surface area, and the therapeutic effect is significant. The multilayer structure of black phosphorus nanosheets certainly provides convenience for loading a large amount of drugs, but the existence of this structure also makes it easy to be oxidized by oxygen in an aqueous environment, which obviously limits its further application in biomedicine. In order to better solve this kind of problem, modifying black phosphorus nanosheets with specific functional groups is a reliable method.

At present, black phosphorus nanosheets are widely used in medical-related fields, especially in the treatment of tumors and neurodegenerative diseases. Research on black phosphorus nanosheets in sterilization will gradually become a hot topic in the industry. The physical structure of black phosphorus nanosheets is similar to that of graphene materials (GMs). The extreme similarity of the structure makes the functions of the two materials have something in common. Chen et al. (Chen J N, et al. Nanoscale 2014, 6, 1879-1889) observed that two-dimensional multilayer materials have sharp edges, which cause the leakage of genetic materials such as RNA in the cell membrane after close contact with the bacterial cell membrane. Luo et al. (Luo Y, et al. J. Am. Chem. Soc. 2016, 138, 2064-2077) also confirmed through relevant experiments that two-dimensional multilayer nanomaterials can pierce the cell membrane of bacteria, causing physical damage to the cell membrane, thereby causing a large amount of leakage of the intracellular matrix and causing bacterial death.

Benzalkonium chloride is a commonly used broad-spectrum antibacterial agent and a cationic surfactant. It has the characteristics of fast binding to proteins and low toxicity. It can change the permeability of bacterial cell membranes, causing substances in the bacterial cytoplasm to leak out, hindering the normal metabolic process of bacteria and causing bacterial death.

Band-Aids are an essential medical product that people often use in their daily lives. They are rectangular in appearance, with a gauze tape soaked in medicine applied in the middle, which can stop bleeding and protect wounds. However, as more and more people need to use Band-Aids, some of its disadvantages are gradually exposed. First of all, the air permeability of adhesive tape-type Band-Aids is generally average, and the water vapor and sweat normally secreted by the wound area cannot pass through this layer of adhesive tape, causing the wound area to be soaked, which has an adverse effect on the skin. Secondly, some Band-Aids have poor waterproof properties. Once the applied area comes into contact with liquid, the Band-Aid will easily become ineffective, and bacteria will be able to enter the wound again, which will prolong the healing time.

Based on these shortcomings, liquid bandages came into being. Compared with traditional bandages, the use of liquid bandages is mainly based on smearing or spraying, and then the medicine will form a thin film at the wound site, which is waterproof and has good air permeability. From the perspective of the currently disclosed patents, liquid bandages still have aspects that need to be improved. For example, the Chinese patent with publication number CN106924803A, in the prepared liquid bandage, the main component of the antibacterial agent is silver nanoparticles. It is effective to use silver for sterilization, but after long-term use, silver will enter the internal environment with blood circulation, causing harm to human health. Another example is the Chinese patent with publication number CN109464696A, which discloses a spray-type liquid bandage, and the obtained product has good waterproof performance and can prevent secondary infection of wounds. The film-forming material of the liquid bandage is mainly polyvinyl alcohol substances. It is worth noting that polyvinyl alcohol substances are slow in film formation and have general air permeability.

Summary of the invention

The purpose of the present invention is to provide a liquid bandage containing black phosphorus nanosheets and a preparation method thereof. The synthesized liquid bandage containing black phosphorus nanosheets is easy to use, forms a film quickly, has excellent antibacterial effect, and due to its own degradability and high biocompatibility, can minimize the harm to the human body. This liquid bandage containing black phosphorus nanosheets, which has both hemostatic, antibacterial, anti-inflammatory functions and moisturizing and skin care effects, is expected to become a new type of medical hygienic wound care material.

In order to achieve the above-mentioned invention object, the present invention adopts the following technical scheme:

A liquid band-aid containing black phosphorus nanosheets, the raw materials of which include, by weight: 5-25 parts of film-forming material, 25-70 parts of solvent, 0.4-3 parts of adhesion promoter, 0.1-4 parts of local anesthetic, 0.5-3 parts of antibacterial agent, 0.5-3 parts of anti-inflammatory agent, 0.3-1 parts of moisturizing agent and 0.2-1 parts of fragrance.

Preferably, the liquid bandage is composed of the following raw materials in parts by weight: 10-25 parts of film-forming substance, 25-65 parts of solvent, 0.6-2 parts of adhesion promoter, 0.2-3 parts of local anesthetic, 1-3 parts of antibacterial agent, 0.5-2 parts of anti-inflammatory agent, 0.5-1 parts of moisturizer and 0.5-1 parts of fragrance.

Preferably, the film-forming substance is a mixture of Pluronic and chitosan, and the mass ratio of the two is (0.3-0.7): (0.3-0.7).

Preferably, the Pluronic is selected from one of Pluronic F68, Pluronic F127, Pluronic F108, Pluronic L92, or a mixture of two or more thereof in any proportion.

Preferably, the Pluronic is a mixture of Pluronic F68 and Pluronic F127.

Preferably, the solvent is a mixture of n-butyl acetate, isopentane, hexamethyldisiloxane and deionized water. Preferably, the adhesion promoter is dopamine.

Preferably, the local anesthetic is a mixture of levobupivacaine and lidocaine.

Preferably, the antibacterial agent is a mixture of black phosphorus nanosheets and benzalkonium chloride.

Preferably, the anti-inflammatory agent is a mixture of aloe extract and chrysanthemum extract.

Preferably, the humectant is a mixture of glycerol and polyethylene glycol;

Preferably, the fragrance is rose essential oil.

Preferably, the method for preparing the black phosphorus nanosheets comprises the following steps:

i) first placing a block of black phosphorus with an intact surface in a saturated sodium hydroxide solution containing methyl pyrrolidone to obtain a mixed solution;

ii) subjecting the mixed solution obtained in step i) to water bath ultrasound for 3 to 10 hours and then allowing it to stand to obtain a brown suspension; iii) centrifuging the brown suspension obtained in step ii) at a speed of 2000 to 4000 rpm for 5 to 15 minutes, collecting the supernatant, and obtaining two-dimensional black phosphorus nanosheets.

The method for preparing the liquid bandage containing black phosphorus nanosheets comprises the following steps:

ⅰ) preparing black phosphorus nanosheets;

ii) adding Pluronic and chitosan to deionized water and allowing to stand to obtain solution A;

iii) adding black phosphorus nanosheets, benzalkonium chloride, n-butyl acetate, isopentane and hexamethyldisiloxane to deionized water in order by weight, and ultrasonically dispersing for 15 to 20 minutes to obtain a solution B;

iv) adding dopamine, aloe extract, bitter chrysanthemum extract, levobupivacaine and lidocaine to solution B in parts by weight, stirring thoroughly to obtain solution C;

v) Slowly adding solution C into solution A and stirring thoroughly until the mixture is uniformly mixed to obtain solution D;

ⅵ) adding polyethylene glycol, glycerol and essential oil into solution D according to their weight parts, stirring and letting stand to obtain the liquid adhesive bandage of the present invention.

Brief introduction to the components and functions involved in the present invention:

1. Pluronic

[Properties] This product, also known as poloxamer, is a polyoxyethylene polyoxypropylene ether block copolymer, a white or slightly yellow translucent solid, easily soluble in water, and has a certain foaming property after dissolution. It is an effective temperature-sensitive polymer material.

【Function】Film-forming substance

2. Chitosan

[Properties] This product is off-white powder, odorless and tasteless. Pure chitosan is a white or off-white translucent flaky solid, with the characteristics of biodegradability, biocompatibility and non-toxicity.

【Function】Film-forming substance

3. Black phosphorus nanosheets

[Properties] This product is a two-dimensional multilayer material made of black phosphorus by liquid phase exfoliation. Black phosphorus is a black crystal with a metallic luster. It is formed by converting white phosphorus under very high pressure and high temperature. It will not spontaneously combust in the air.

【Function】Antibacterial agent

4. Butyl acetate

[Properties] This product is a colorless, transparent liquid with a pleasant fruity odor, and is an excellent organic solvent. It should be stored in a cool, ventilated warehouse, away from fire and heat sources.

【Function】Solvent

5. Isopentane

[Properties] This product is a colorless, transparent, volatile liquid with a pleasant aromatic odor. It is mainly used in organic synthesis and also as a solvent. It should be stored in a ventilated, low-temperature, dry place and separated from oxidants and acids.

【Function】Solvent

6. Hexamethyldisiloxane [Properties] This product is a colorless, transparent liquid, soluble in a variety of organic solvents.

【Function】Solvent

7. Dopamine

[Properties] This product is the most abundant catecholamine neurotransmitter in the brain. As a neurotransmitter, dopamine regulates various physiological functions of the central nervous system. At the same time, dopamine has adhesion, reducing properties and good biocompatibility.

【Function】Adhesion promoter

8. Levobupivacaine

[Properties] This product is a single isomer of bupivacaine, which has better safety and less central nervous system and cardiac toxicity than bupivacaine. It can be used for local or regional anesthesia in surgery, as well as postoperative pain control.

【Function】Local anesthetic

9. Lidocaine

[Properties] This product is a local anesthetic and antiarrhythmic drug. It is a derivative of cocaine, easily soluble in water, and has the same toxicity as procaine, but has a stronger and more lasting local anesthetic effect, good surface penetration, and can be injected or used as a surface anesthesia.

【Function】Local anesthetic

10. Benzalkonium chloride

[Properties] This product is a white waxy solid or yellow colloid. Its aqueous solution shows a neutral or weakly alkaline reaction and produces a lot of foam when shaken. This product is easily soluble in water or ethanol and is an important cationic quaternary ammonium surfactant. It is widely used in personal care, hair conditioner and other products. It has good antistatic, softening and antiseptic effects. It can also be used in sterilization, printing and dyeing auxiliaries, and other industries.

【Function】Antibacterial agent

11. Aloe Vera

[Properties] This product is one of the few edible species in the genus Aloe. Its products are widely used in food, beauty, health care, medicine and other fields. It is an evergreen, fleshy herb with a short stem. Aloe juice preparations have a protective effect on skin trauma, burns and local X-ray irradiation.

【Function】Anti-inflammatory agent

12. Chrysanthemum

[Properties] This fruit tastes sweet with a slight bitterness and is green in color. It can be stir-fried or served cold. It is a great delicacy for clearing away heat and removing internal heat. It also has antibacterial, antipyretic, anti-inflammatory, and eye-improving effects.

【Function】Anti-inflammatory agent

13. Glycerin

[Properties] This product is also called propylene glycol. It is colorless, odorless, sweet, and appears as a clear, viscous liquid. It can be dissolved in water in any proportion.

【Function】Moisturizer

14. Polyethylene glycol

[Properties] This product is non-toxic, non-irritating, slightly bitter, has good water solubility, and has good compatibility with many organic components. They have excellent lubricity, moisturizing and dispersibility, and are widely used in cosmetics, pharmaceuticals, and food processing industries.

【Function】Moisturizer

15. Rose essential oil

[Properties] This product is a volatile aromatic substance extracted from rose petals by extrusion, cold soaking or solvent extraction.

【Function】Fragrance

Compared with the prior art, the present invention has the following advantages:

(1) The present invention uses black phosphorus nanosheets as antibacterial agents, and utilizes their physical antibacterial ability to cooperate with benzalkonium chloride to achieve a joint sterilization effect. In addition, the black phosphorus nanosheets have good self-degradability and high biocompatibility, which to a certain extent alleviates the harm of benzalkonium chloride to the body.

(2) The present invention uses a mixture of pluronic and chitosan as a film-forming substance. The addition of pluronic makes the solution-gel phase transition point of the liquid bandage more dependent on the body's own temperature, so the dependence on the rapid volatilization of the organic solvent to form a film is greatly reduced, and the irritation to the wound site is also reduced to a corresponding degree.

(3) The adhesion promoter described in the present invention is dopamine, which is one of the components of the adhesive protein secreted by marine mussels. Dopamine can undergo oxidative self-polymerization reaction in aqueous solution to form polydopamine, which has excellent adhesion and biocompatibility and can improve the adhesion ability of liquid bandages to wound sites.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a water contact angle measurement of the liquid adhesive bandage prepared in Comparative Example 1.

FIG. 2 is a graph showing the water contact angle measurements of the liquid adhesive bandages prepared in Examples 1-6.

FIG3 shows H&E staining of the mouse skin area treated with the liquid band-aid prepared in Example 1.

FIG4 is H&E staining of the heart, liver, spleen, lung and kidney of mice treated with the liquid band-aid prepared in Example 1. FIG.

DETAILED DESCRIPTION

In order to further understand the present invention, preferred embodiments of the present invention are described below in conjunction with examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present invention, rather than limiting the claims of the present invention.

The invention discloses a liquid bandage containing black phosphorus nanosheet components and a preparation method thereof.

The liquid band-aid of the present invention is composed of the following raw materials in parts by weight: 5-25 parts of film-forming substance, 25-70 parts of solvent, 0.4-3 parts of adhesion promoter, 0.1-4 parts of local anesthetic, 0.5-3 parts of antibacterial agent, 0.5-3 parts of anti-inflammatory agent, 0.3-1 parts of moisturizing agent and 0.2-1 parts of fragrance.

The preparation method of the liquid adhesive bandage comprises the following steps:

ⅰ) preparing black phosphorus nanosheets;

ii) adding Pluronic and chitosan to deionized water and allowing to stand to obtain solution A;

iii) adding black phosphorus nanosheets, benzalkonium chloride, n-butyl acetate, isopentane and hexamethyldisiloxane to deionized water in order by weight, and ultrasonically dispersing for 15 to 20 minutes to obtain a solution B;

iv) adding dopamine, aloe extract, bitter chrysanthemum extract, levobupivacaine and lidocaine to solution B in parts by weight, stirring thoroughly to obtain solution C;

v) Slowly adding solution C into solution A and stirring thoroughly until the mixture is uniformly mixed to obtain solution D;

ⅵ) adding polyethylene glycol, glycerol and essential oil into solution D according to their weight parts, stirring and letting stand to obtain the liquid adhesive bandage of the present invention.

The method for preparing the black phosphorus nanosheets comprises the following steps:

i) firstly placing the blocky black phosphorus with intact surface into a saturated sodium hydroxide solution (0.5 mg/mL) containing methyl pyrrolidone to obtain a mixed solution;

ii) subjecting the mixed solution obtained in step i) to water bath sonication for 3 h and then allowing it to stand to obtain a brown suspension;

iii) The brown suspension obtained in step ii) was centrifuged at 2000 rpm for 5 min, and the supernatant was collected to obtain two-dimensional black phosphorus nanosheets (0.5 mg/mL).

Aloe vera extract was purchased from Hunan Denuo Health Industry Group Co., Ltd., and bitter chrysanthemum extract was purchased from Shaanxi Qinglan Biotechnology Co., Ltd.

The preparation method of the aloe extract comprises the following steps:

ⅰ) First, clean the fresh aloe vera with thick flesh, split it in half with a knife, and then use a spoon to gently scrape out the fresh flesh inside the aloe vera;

ii) putting the fresh aloe vera obtained in step i) into a clean container and stirring until fine bubbles are generated;

iii) extracting the aloe mucus obtained in step ii) with a mixed solution of urea and choline chloride (mass ratio of 1:30), adding anhydrous ethanol, standing for alcohol precipitation, and centrifuging to obtain the supernatant to obtain an aloe extract.

The preparation method of the bitter chrysanthemum extract comprises the following steps:

i) extracting the dried whole herb of bitter chrysanthemum by reflux extraction with 95% ethanol (0.075 kg/L) for three times, each time for two hours, filtering and combining the filtrates, concentrating under reduced pressure, and suspending the mixture in a 70% ethanol solution to obtain a suspension I;

ii) extracting the suspension obtained in step i) with petroleum ether for 4 times until no alcohol smell is left, then suspending with water, and extracting with ethyl acetate for 3 times to obtain suspension II;

iii) passing the suspension II obtained in step ii) through a macroporous adsorption resin, concentrating the precipitate and drying it to obtain brown powder particles, which are bitter chrysanthemum extract.

The present invention is further described below in conjunction with specific examples. The comparative samples used in the examples are prepared according to the preparation method described in the published Chinese patent CN108785739A. The liquid bandage prepared by this method has rapid film formation, good antibacterial effect, good air permeability, and low irritation. In addition to the film formation time and skin wound irritation tests of the liquid bandage, the tests on the performance of the liquid bandage were carried out according to the following relevant standards:

Air permeability: measured in accordance with the method specified in the pharmaceutical industry standard YY/T 0471.2-2004 of the People's Republic of China regarding the water vapor permeability of breathable film dressings.

Water barrier property: Determined in accordance with the method for water barrier property specified in the pharmaceutical industry standard YY/T 0471.3-2004 of the People's Republic of China.

Bacterial barrier properties: The test was carried out in accordance with the method specified in the pharmaceutical industry standard YY/T 0471.5-2004 of the People's Republic of China on bacterial barrier properties.

Hemolysis test: The test was conducted in accordance with the method specified in the National Standard of the People's Republic of China GB T 16886.4-2003 on "Biological Evaluation of Medical Devices: Selection of Tests for Interactions with Blood".

Cytotoxicity test: The test was conducted in accordance with the method specified in the National Standard of the People's Republic of China GB T 16886.5-2003 on "Biological Evaluation of Medical Devices: In Vitro Cytotoxicity Test".

Example 1

ⅰ) preparing black phosphorus nanosheets;

ii) adding 8 parts by weight of Pluronic and 12 parts by weight of chitosan to 40 parts by weight of deionized water, and letting the mixture stand to obtain a solution A;

iii) adding 2 parts by weight of black phosphorus nanosheets (0.5 mg/mL), 1 part by weight of benzalkonium chloride, 10 parts by weight of n-butyl acetate, 25 parts by weight of isopentane, and 15 parts by weight of hexamethyldisiloxane to 60 parts by weight of deionized water in sequence, and ultrasonically dispersing for 15 to 20 minutes to obtain a solution B;

iv) adding 2 parts by weight of dopamine, 0.5 parts by weight of aloe extract, 1 part by weight of bitter chrysanthemum extract, 0.5 parts by weight of levobupivacaine and 0.5 parts by weight of lidocaine to solution B, stirring well to obtain solution C;

v) Slowly adding solution C into solution A and stirring thoroughly until the mixture is uniformly mixed to obtain solution D;

ⅵ) 0.2 parts by weight of polyethylene glycol, 0.5 parts by weight of glycerol and 0.4 parts by weight of rose essential oil are added to solution D, stirred and allowed to stand to obtain the liquid adhesive bandage of the present invention.

Example 2

ⅰ) preparing black phosphorus nanosheets;

ii) adding 12 parts by weight of Pluronic and 8 parts by weight of chitosan to 40 parts by weight of deionized water, and letting the mixture stand to obtain a solution A;

iii) adding 2 parts by weight of black phosphorus nanosheets (0.5 mg/mL), 1 part by weight of benzalkonium chloride, 15 parts by weight of n-butyl acetate, 20 parts by weight of isopentane, and 20 parts by weight of hexamethyldisiloxane to 60 parts by weight of deionized water in sequence, and ultrasonically dispersing for 15 to 20 minutes to obtain a solution B;

iv) adding 2 parts by weight of dopamine, 1 part by weight of aloe extract, 0.5 parts by weight of bitter chrysanthemum extract, 0.5 parts by weight of levobupivacaine and 0.5 parts by weight of lidocaine to solution B, and stirring well to obtain solution C;

v) Slowly adding solution C into solution A and stirring thoroughly until the mixture is uniformly mixed to obtain solution D;

ⅵ) 0.3 parts by weight of polyethylene glycol, 0.6 parts by weight of glycerol and 0.5 parts by weight of rose essential oil are added to solution D, stirred and allowed to stand to obtain the liquid adhesive bandage of the present invention.

Example 3

ⅰ) preparing black phosphorus nanosheets;

ii) adding 8 parts by weight of Pluronic and 12 parts by weight of chitosan to 40 parts by weight of deionized water, and letting the mixture stand to obtain a solution A;

iii) adding 1.5 parts by weight of black phosphorus nanosheets (0.5 mg/mL), 1.5 parts by weight of benzalkonium chloride, 20 parts by weight of n-butyl acetate, 30 parts by weight of isopentane, and 15 parts by weight of hexamethyldisiloxane to 60 parts by weight of deionized water, and ultrasonically dispersing for 15 to 20 minutes to obtain a solution B;

iv) adding 2 parts by weight of dopamine, 1 part by weight of aloe extract, 1 part by weight of bitter chrysanthemum extract, 0.5 parts by weight of levobupivacaine and 0.5 parts by weight of lidocaine to solution B, and stirring well to obtain solution C;

v) Slowly adding solution C into solution A and stirring thoroughly until the mixture is uniformly mixed to obtain solution D;

ⅵ) 0.2 parts by weight of polyethylene glycol, 0.6 parts by weight of glycerol and 0.6 parts by weight of rose essential oil are added to solution D, stirred and allowed to stand to obtain the liquid adhesive bandage of the present invention.

Example 4

ⅰ) preparing black phosphorus nanosheets;

ii) adding 8 parts by weight of Pluronic and 12 parts by weight of chitosan to 40 parts by weight of deionized water, and letting the mixture stand to obtain a solution A;

iii) adding 2 parts by weight of black phosphorus nanosheets (0.5 mg/mL), 1 part by weight of benzalkonium chloride, 15 parts by weight of n-butyl acetate, 25 parts by weight of isopentane, and 20 parts by weight of hexamethyldisiloxane to 60 parts by weight of deionized water in order by weight, and ultrasonically dispersing for 15 to 20 minutes to obtain a solution B;

iv) adding 3 parts by weight of dopamine, 1 part by weight of aloe extract, 2 parts by weight of bitter chrysanthemum extract, 0.5 parts by weight of levobupivacaine and 0.5 parts by weight of lidocaine to solution B, stirring well to obtain solution C;

v) Slowly adding solution C into solution A and stirring thoroughly until the mixture is uniformly mixed to obtain solution D;

ⅵ) 0.3 parts by weight of polyethylene glycol, 0.5 parts by weight of glycerol and 0.4 parts by weight of rose essential oil are added to solution D, stirred and allowed to stand to obtain the liquid adhesive bandage of the present invention.

Example 5

ⅰ) preparing black phosphorus nanosheets;

ii) adding 8 parts by weight of Pluronic and 12 parts by weight of chitosan to 40 parts by weight of deionized water, and letting the mixture stand to obtain a solution A;

iii) adding 2 parts by weight of black phosphorus nanosheets (0.5 mg/mL), 1 part by weight of benzalkonium chloride, 15 parts by weight of n-butyl acetate, 25 parts by weight of isopentane, and 20 parts by weight of hexamethyldisiloxane to 60 parts by weight of deionized water in order by weight, and ultrasonically dispersing for 15 to 20 minutes to obtain a solution B;

iv) adding 2 parts by weight of dopamine, 2 parts by weight of aloe extract, 0.5 parts by weight of bitter chrysanthemum extract, 2 parts by weight of levobupivacaine and 1 part by weight of lidocaine to solution B, stirring well to obtain solution C;

v) Slowly adding solution C into solution A and stirring thoroughly until the mixture is uniformly mixed to obtain solution D;

ⅵ) 0.2 parts by weight of polyethylene glycol, 0.7 parts by weight of glycerol and 0.7 parts by weight of rose essential oil are added to solution D, stirred and allowed to stand to obtain the liquid adhesive bandage of the present invention.

Example 6

ⅰ) preparing black phosphorus nanosheets;

ii) adding 8 parts by weight of Pluronic and 12 parts by weight of chitosan to 40 parts by weight of deionized water, and letting the mixture stand to obtain a solution A;

iii) adding 2 parts by weight of black phosphorus nanosheets (0.5 mg/mL), 0.5 parts by weight of benzalkonium chloride, 10 parts by weight of n-butyl acetate, 25 parts by weight of isopentane, and 15 parts by weight of hexamethyldisiloxane to 60 parts by weight of deionized water in sequence, and ultrasonically dispersing for 15 to 20 minutes to obtain a solution B;

iv) adding 2 parts by weight of dopamine, 0.5 parts by weight of aloe extract, 1 part by weight of bitter chrysanthemum extract, 0.5 parts by weight of levobupivacaine and 0.5 parts by weight of lidocaine to solution B, stirring well to obtain solution C;

v) Slowly adding solution C into solution A and stirring thoroughly until the mixture is uniformly mixed to obtain solution D;

ⅵ) 0.2 parts by weight of polyethylene glycol, 0.5 parts by weight of glycerol and 0.4 parts by weight of rose essential oil are added to solution D, stirred and allowed to stand to obtain the liquid adhesive bandage of the present invention.

Control group 1

The liquid band-aid used in this control group was prepared according to the published Chinese patent CN108785739A. The preparation method can be found in the detailed content of the patent.

Performance testing and experiment of the liquid bandage of the present invention

1. Liquid Band-Aid Film Forming Time Test

After the preparation of the liquid bandages described in Examples 1-6 and Control Group 1, the liquid bandages were bottled, each containing 20 g, and stored at 37°C for 0 days, 7 days, 15 days, and 30 days. Afterwards, the film-forming time was tested. The film-forming time was tested by applying the liquid bandage on the arm and then starting the timing. The results are shown in Table 1.

Table 1 Film-forming time of liquid band-aids with different ingredients

It can be seen from Table 1 that after one month, the film-forming time of Examples 1-6 is shorter than that of Control Group 1, and the film-forming time of Examples 1-6 does not change much with the increase of storage time.

2. Test on the irritation of liquid bandage to skin wound

After the preparation, the liquid bandages described in Examples 1-6 and Control Group 1 were applied to small wounds on the arms of 35 testers, and the testers' feelings during the application and the skin conditions after 1 day were recorded. The 35 testers were divided into 7 groups, each with 5 people, and each person had a small wound on his or her arm. The results are shown in Table 2.

Table 2 Irritation of different liquid band-aids to skin wounds

As can be seen from Table 2, the liquid bandages described in Examples 1-6 showed normal skin conditions both during application and one day later, indicating that the liquid bandages described in the present invention have low skin irritation. However, when the liquid bandage of Control Group 1 was applied to the small wounds of the test subjects, more than half of the test subjects said that they felt a stinging sensation at the skin wounds.

The irritation of the present invention to the human body was further evaluated according to the scoring standards described in Table 3 and Table 4.

Table 3 Skin irritation reaction scores

Table 4 Skin irritation intensity classification

Integral mean strength 0.0-0.5 Non-irritating 0.5-2.0 Mild irritation 2.0-6.0 Moderate irritation 6.0-8.0 Strong irritation

The experimental results show that the samples used in the present invention do not form erythema and edema, and the skin irritation intensity classification shows that they are non-irritating.

3. Water-blocking and antibacterial properties test of liquid bandages

The test was conducted according to the test methods specified in the pharmaceutical industry standards YY/T 0471.3-2004 and YY/T 0471.5-2004 of the People's Republic of China. The results are shown in Table 5.

Table 5 Water barrier and bacteria barrier test of liquid bandage

In order to further test the in vitro bacterial growth inhibition effect of the liquid bandage, 20 μL of the liquid bandage described in Examples 1-6 and Control Group 1 was taken for the antibacterial zone experiment after the preparation. The experimental bacteria used were Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). The results are shown in Table 6.

Table 6 Antibacterial activity of Bacillus

It can be seen from Table 5 and Table 6 that the liquid bandages described in Examples 1-6 can effectively prevent moisture and bacteria from invading the wound, indicating that the liquid bandages described in the present invention have good waterproof and antibacterial properties.

Has strong and effective antibacterial effect

4. Hemolysis test of liquid bandage

5. Cytotoxicity test of liquid bandage

Judgment criteria: The corresponding part of "Final Judgment of Toxicology Test Results" in the first volume of "Disinfection Technical Specifications" (3rd edition) "Experimental Technical Specifications" (1999) of the Ministry of Health shall be used as the judgment principle for test results.

6. Transparency Experiment

The transparency of the prepared liquid bandage was determined by the following test method: 10 subjects aged 18 to 55 were selected, and the prepared liquid bandage samples were evenly applied on the skin surface of the subjects' arms to observe the changes in the transparency of the liquid bandage. The specific experimental results are shown in the table below:

Table 7 Transparency test of liquid bandage

Subjects Transparency No.1 Good transparency, wounds can be observed No.2 Good transparency, wounds can be observed No.3 Good transparency, wounds can be observed No.4 Good transparency, wounds can be observed No.5 Good transparency, wounds can be observed No.6 Good transparency, wounds can be observed No.7 Good transparency, wounds can be observed No.8 Good transparency, wounds can be observed No.9 Good transparency, wounds can be observed No.10 Good transparency, wounds can be observed

The test results of 10 subjects show that after application, the liquid Band-Aid has good transparency and the changes of the wound can be clearly observed in real time.

7. Sol-gel conversion time

The test method for the determination of the sol-gel transition time of the prepared liquid bandage is as follows: 10 subjects aged 18 to 55 are selected, and 0.5g of the prepared liquid bandage sample is evenly applied on the skin surface of the back of the subject's hand, and the solution-gel transition time is recorded each time, and the average value is calculated. The specific experimental data are shown in the following table:

Table 8 Sol-gel transition time of liquid bandage

8. Contact angle test

The size of the contact angle reflects the wettability of the surface of the wound dressing. Good hydrophilicity means that the dressing can provide sufficient wettability to the wound surface, which is beneficial to the proliferation of cells at the wound site and promotes wound healing.

The contact angle of the prepared liquid Band-Aid was measured by the following test method: the liquid Band-Aid was evenly spread on a glass slide and dried in an oven at 37°C; the contact angle of the film formed by the liquid Band-Aid was measured using a contact angle meter. It is worth noting that 6 liquid Band-Aid films were used for the measurement, and 3 points were taken at different positions on each film. The average value of the measured contact angles was taken. The results are shown in Figure 2.

9. Biosafety Testing

Good biosafety is a characteristic that drugs that come into direct contact with human skin must possess. The biosafety of the prepared liquid band-aid was tested. The test method was to first construct a mouse skin trauma model: 120 μL of 1% sodium pentobarbital reagent was injected intraperitoneally to remove the mouse hair, and then cultured in a dry and clean environment for 12 hours, and a skin excision wound with a diameter of 8 mm was made on the back of the mouse using a puncher. At the same time, another mouse in a healthy state was used as a control group. Then the wound was treated with the prepared liquid band-aid. The liquid band-aid prepared in Example 1 was used to perform H&E staining on the treated skin area and the heart, liver, spleen, lungs and kidneys. The results are shown in Figures 3 and 4: Figure 3 shows the healing of the wounds of the test mice within fourteen days after surgery. The healing process of the wound area of the mice smeared with the liquid band-aid can be seen. On the fourteenth day, the epidermis and dermis of the wound site were almost completely repaired, and some hair follicles grew out; Figure 4 shows the biosafety assessment of mice sacrificed fourteen days after surgery. Through H&E staining analysis of the heart, liver, spleen, lung and kidney organs of the mice, the cell proliferation of the mice with liquid bandages applied to the wound site was not significantly different from that of the control group. Based on the above test results, it can be fully demonstrated that the prepared liquid bandage has good biosafety.

As can be seen from Table 1, compared with Comparative Example 1, Examples 1-6 increase the concentration of Planckner and chitosan, so that the system has highly reactive groups such as hydroxyl and amino groups, which is conducive to the subsequent improvement of the chemical reaction ability of reacting with other substances during the stirring process, and the film-forming time can be effectively reduced. Compared with Example 1 and Examples 3-6, the increase in the concentration of Planckner in Example 2 can effectively improve the film-forming efficiency. As can be seen from Table 2 and Table 6, compared with Comparative Example 1, Examples 1-6 add natural anti-inflammatory agents such as aloe vera and bitter chrysanthemum and levobupivacaine local anesthetics, which can not only reduce the irritation of the wound surface, but also effectively prevent bacteria from invading the wound and avoid further bacterial infection. As can be seen from Figures 1 and 2, compared with Comparative Example 1, the liquid band-aid prepared by Examples 1-6 has excellent hydrophilic properties, which is because the liquid band-aid is provided with hydroxyl, amino and oxygen-containing groups and other groups such as ether bonds by adding chitosan and surfactants, giving full play to the synergistic function of two different types of surfactants, and jointly promoting the liquid band-aid to protect the wound and promote healing.

The above-described embodiments are for demonstration purposes only and are not intended to limit the present invention in any form. It should be understood that, without exceeding the spirit and technical scope of the present invention, the technicians of the present invention may make various substitutions and improvements within the scope, and these substitutions and improvements are within the protection scope of the present invention.

Claims (7)

1. The liquid band-aid containing the black phosphorus nano sheet component is characterized by comprising the following raw materials in parts by weight: 5 to 25 parts of film forming substances, 25 to 70 parts of solvents, 0.4 to 3 parts of adhesion promoters, 0.1 to 4 parts of local anesthetics, 0.5 to 3 parts of antibacterial agents, 0.5 to 3 parts of anti-inflammatory agents, 0.3 to 1 part of moisturizers and 0.2 to 1 part of aromatic agents;

The film forming material is a mixture of pluronic and chitosan, and the mass ratio of the pluronic to the chitosan is (0.3-0.7): (0.3 to 0.7);

The antibacterial agent is a mixture of black phosphorus nano-sheets and benzalkonium chloride;

The preparation method of the liquid band-aid containing the black phosphorus nano sheet component comprises the following steps:

i) preparing black phosphorus nano-sheets;

ii) adding pluronic and chitosan into deionized water, and standing to obtain a solution A;

iii) sequentially adding black phosphorus nano-sheets, benzalkonium chloride, n-butyl acetate, isopentane and hexamethyldisiloxane into deionized water according to parts by weight, and performing ultrasonic dispersion for 15-20 min to obtain a solution B;

Iv) adding dopamine, aloe extract, chamomile extract, levobupivacaine and lidocaine into the solution B according to parts by weight, and fully stirring to obtain a solution C;

V) slowly adding the solution C into the solution A, and fully stirring until the solution C is uniformly mixed to obtain a solution D;

Vi) adding polyethylene glycol, glycerol and essential oil into the solution D according to parts by weight, stirring, and standing to obtain the liquid band-aid.

2. The liquid adhesive bandage with black phosphorus nanoplatelets according to claim 1, wherein the solvent is a mixture of n-butyl acetate, isopentane, hexamethyldisiloxane, deionized water.

3. A liquid band-aid comprising black phosphorus nanoplatelets as in claim 1 wherein the adhesion promoter is dopamine.

4. A liquid band-aid comprising black phosphorus nanoplatelets as in claim 1 wherein the local anesthetic is a mixture of levobupivacaine and lidocaine.

5. The liquid band-aid containing black phosphorus nano-sheets according to claim 1, wherein the preparation method of the black phosphorus nano-sheets comprises the following steps:

firstly, putting the blocky black phosphorus with complete surface into saturated sodium hydroxide solution containing methyl pyrrolidone to obtain mixed solution;

Ii) carrying out water bath ultrasonic treatment on the mixed solution obtained in the step i) for 3-10 h, and standing to obtain brown suspension;

Iii) centrifuging the brown suspension obtained in the step ii) at a rotation speed of 2000-4000 rpm for 5-15 min, and collecting supernatant to obtain the two-dimensional black phosphorus nanoplatelets.

6. The liquid band-aid of claim 1, wherein the anti-inflammatory agent is a mixture of aloe vera extract and chamomile extract.

7. The liquid band-aid containing black phosphorus nanoplatelets as in claim 1, wherein the humectant is a mixture of glycerin and polyethylene glycol; the aromatic is essential oil.