CN114732942A - Chlorine dioxide slow-release liquid band-aid and preparation method thereof - Google Patents

Abstract

The invention provides a chlorine dioxide sustained-release liquid Band-Aid and a preparation method thereof. The Band-Aid comprises the following components in parts by weight: 20-30 parts of acrylic acid/N-vinylpyrrolidone hydrogel, 24-36 parts of isopropanol parts, 8-12 parts of butyl acetate, 8-12 parts of amyl acetate, 2-5 parts of castor oil, 0.2-3 parts of tocopheryl acetate, 2-8 parts of benzyl alcohol, 5-20 parts of chlorine dioxide, 3-5 parts of pharmaceutical grade azone. The band-aid has good antibacterial properties, has obvious inhibitory activity against the growth of various pathogenic bacteria, and has both waterproof and breathable properties. The selected film-forming material can realize the sustained release of chlorine dioxide on the wound surface, prolong the effect and reduce the The number of administrations can also reduce drug residues, prevent wound bacteria from developing drug resistance, effectively promote wound healing, and can effectively solve the problem of poor bacteriostatic effect and large amount of antibacterial drugs in existing wound dressings, resulting in drug resistance of wound surface bacteria. The problem.

Description

A chlorine dioxide sustained-release liquid band-aid and preparation method thereof

technical field

The invention belongs to the technical field of band-aids, and in particular relates to a chlorine dioxide sustained-release liquid band-aid and a preparation method thereof.

Background technique

In daily life, minor skin abrasions, scratches, cuts and other wounds are very common. For such wounds, people generally use traditional band-aids for simple application. However, the shortcomings of traditional band-aids are: it can cause skin to appear in a few people. Allergic reaction; adhesion of the wound, resulting in mechanical re-injury during replacement; limited absorption capacity; not waterproof, easily penetrated by bacteria and susceptible to infection, and scabs hinder the healing of the wound; the application site is white due to the tape bandage; large and small area coverage and movement Site restrictions, etc. In order to solve the above problems, there are currently liquid Band-Aid products on the market. Liquid Band-Aid is a bottled medicine made by dissolving film-forming materials in a solvent. It can be tightly adhered to the skin surface by spraying or smearing. Contact will not occur penetration, can play a good role in wound protection.

However, the current liquid Band-Aid still has shortcomings. For example, as a wound dressing, the antibacterial substances in the product are 8-hydroxyquinoline, benzalkonium chloride, doxycycline and other materials. Such antibacterial materials It will have toxic and side effects on the human body and cause allergic reactions; the antibacterial dose added to the product is large but the effective time is short. Excessive antibacterial drugs on the wound surface will lead to drug resistance of bacteria on the wound surface over time, which is particularly unfavorable for the healing of chronic wounds such as diabetic foot and bedsores, and may even aggravate the disease due to bacterial resistance. In addition, the hemostatic properties of the product are poor.

Chlorine dioxide is a safe, efficient, broad-spectrum, and powerful disinfectant, and is recognized by the United Nations World Health Organization (WHO) as an A1-level disinfectant. The effective chlorine of chlorine dioxide is 2.63 times that of chlorine gas, the sterilization ability is 5 times that of chlorine gas, and more than 45 times that of sodium hypochlorite. A large number of studies at home and abroad have shown that: the use of low-dose chlorine dioxide has no carcinogenic, teratogenic and mutagenic effects on higher animals and plants. However, the dosage of chlorine dioxide used in the prior art is generally too large, which is likely to cause problems such as skin eczema and skin lesions, which in turn leads to more serious problems.

SUMMARY OF THE INVENTION

In view of the above problems existing in the prior art, the present invention provides a chlorine dioxide sustained-release liquid band-aid and a preparation method thereof. The band-aid has good antibacterial properties, has obvious inhibitory activity against the growth of various pathogenic bacteria, and has both With waterproof and breathable properties, the selected film-forming material can realize the slow release of chlorine dioxide on the wound surface, prolong the effect, reduce the number of administrations and reduce drug residues, avoid the resistance of wound bacteria, and effectively promote wound healing. The invention can effectively solve the problems of poor antibacterial effect and large amount of antibacterial drugs in the existing wound sticks, which lead to drug resistance of bacteria on the wound surface.

For realizing the above-mentioned purpose, the technical scheme that the present invention solves its technical problem adopts is:

A chlorine dioxide sustained-release liquid Band-Aid, comprising the following components by weight: 20-30 parts of acrylic acid/N-vinylpyrrolidone hydrogel, 24-36 parts of isopropanol, 8-12 parts of butyl acetate, 8-12 parts of amyl acetate, 2-5 parts of castor oil, 0.2-3 parts of tocopheryl acetate, 2-8 parts of benzyl alcohol, 5-20 parts of chlorine dioxide, and 3-5 parts of pharmaceutical grade azone.

Further, the following components are included in parts by weight: 30 parts of acrylic acid/N-vinylpyrrolidone hydrogel, 30 parts of isopropanol, 8 parts of butyl acetate, 8 parts of amyl acetate, 5 parts of castor oil, ethyl tocopherol 1 part of acid ester, 5 parts of benzyl alcohol, 15 parts of chlorine dioxide, 3 parts of pharmaceutical grade azone.

Further, the acrylic acid/N-vinylpyrrolidone hydrogel is prepared by the following method: dissolving the N-vinylpyrrolidone in distilled water, keeping for 0.5h, adding acrylic monomer and adding a crosslinking agent and an initiator while stirring, Then react in a sealed water bath environment at 55-65°C for 20-30 hours, take out the product, soak and wash repeatedly with distilled water, fully purify and prepare.

Further, the mass ratio of N-vinylpyrrolidone to acrylic monomer is 3:1, the amount of crosslinking agent is 1.5 wt% of the mass of N-vinylpyrrolidone monomer, and the amount of initiator is N-vinylpyrrolidone monomer. 0.8 wt% of body mass.

Further, the crosslinking agent is N-N' methylenebisacrylamide, and the initiator is potassium persulfate, ammonium persulfate or azobisisobutyronitrile.

Further, 0.5-2 parts of fragrance essential oil are also included.

Further, the fragrance essential oil is lavender essential oil or peppermint essential oil.

The preparation method of the above-mentioned chlorine dioxide sustained-release liquid Band-Aid, comprising the following steps: mixing isoacetone and butyl acetate, adding acrylic acid/N-vinylpyrrolidone hydrogel to it under stirring conditions, then warming up to swelling, The remaining raw materials are added to it, and the reaction is stirred and reacted under the condition of keeping away from light and heat to obtain the product.

Further, the temperature is raised to 40-60°C until fully swollen, the remaining raw materials are added, and then the reaction is stirred at a rotational speed of 300r/min--500r/min under the dark condition of 40-60°C.

Further, the stirring reaction time is 2-4h under the dark condition.

The beneficial effects produced by the present invention are:

In this application, acrylic acid/N-vinylpyrrolidone hydrogel is used to encapsulate chlorine dioxide molecules, which can realize the sustained release effect of chlorine dioxide on the wound surface, prolong the action time of the drug, and reduce the number of administrations, specifically: acrylic acid/N-vinylpyrrolidone hydrogel There is an interpenetrating network structure inside the N-vinylpyrrolidone hydrogel, which is a pH-responsive hydrogel. The three-dimensional network structure of the hydrogel contains a large number of immobile carboxyl groups. At different pH values, the degree of dissociation of carboxyl groups Different, the electrostatic repulsion in the interpenetrating network is different. When there is no infection on the wound surface, the pH value is 5-7. At this time, the hydrogen bond between the carboxyl group and COOH is associated, the hydrogel swelling rate is low, and the drug chlorine dioxide is released. A small amount can prevent inflammation of the wound surface. When the wound is inflamed and the surface of the wound is alkaline, the carboxyl-COOH gradually dissociates into -COO-, the hydrogen bonds in the gel network dissociate, the electrostatic repulsion between ions increases significantly, and the swelling rate increases. Chlorine dioxide molecules in the gel network are released in large quantities, thereby resolving the inflammation on the wound surface. It can be seen that the polymer material in the present invention can achieve pH value response through network interpenetration and entanglement.

The liquid wound patch has strong antibacterial ability. The antibacterial test shows that the product can effectively kill Staphylococcus aureus, Pseudomonas aeruginosa, etc. within 2 minutes. At the same time, chlorine dioxide also has a certain hemostatic ability, which is more conducive to Treatment of wounds.

The liquid wound patch is easy to use, and after simple cleaning of the wound, the product is smeared on the wound site, and the product can quickly form a transparent film. The elastic transparent film formed has good air permeability and wound protection, and it also has good water resistance. Even if it is directly immersed in water, it will not cause penetration. It can combine the continuous disinfection function of the wound surface with the continuous protection function of the wound surface. for one. The transparent film is convenient to observe the wound healing, and after the wound heals, the film can be torn off directly. This product also improves the sterilization, hemostasis, wound healing and other properties of liquid band-aids. While ensuring the effect of use, the material is selected to minimize the production cost and greatly reduce the price of liquid Band-Aid products.

Description of drawings

Fig. 1 is a photo of the peeling process;

Fig. 2 is the bacteriostatic effect figure of Band-Aid in Example 2;

Fig. 3 is the drug release curve diagram of liquid Band-Aid in Example 1-4 and Comparative Example 1-2;

FIG. 4 is the change curve of the swelling rate of the liquid Band-Aid of Example 2 and Comparative Example 2. FIG.

Detailed ways

The specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

Example 1

A chlorine dioxide sustained-release liquid Band-Aid, comprising the following components by weight: 20 parts of acrylic acid/N-vinylpyrrolidone hydrogel, 25 parts of isopropanol, 10 parts of butyl acetate, 10 parts of amyl acetate, 4 parts of castor oil, 3 parts of tocopherol acetate, 6 parts of benzyl alcohol, 10 parts of chlorine dioxide, 5 parts of pharmaceutical grade azone.

The preparation method of above-mentioned chlorine dioxide sustained-release liquid Band-Aid, comprises the following steps:

Mix isoacetone and butyl acetate, add acrylic acid/N-vinylpyrrolidone hydrogel to it under stirring condition, then heat up to 50°C to swell completely, then add the remaining raw materials to it, and keep it at 50°C under the condition of avoiding light and keeping warm. The product was prepared by stirring and reacting for 3h at a rotating speed of 400r/min.

Example 2

A chlorine dioxide sustained-release liquid Band-Aid, comprising the following components by weight: 30 parts of acrylic acid/N-vinylpyrrolidone hydrogel, 30 parts of isopropanol, 8 parts of butyl acetate, 8 parts of amyl acetate, 5 parts of castor oil, 1 part of tocopherol acetate, 5 parts of benzyl alcohol, 15 parts of chlorine dioxide, 3 parts of pharmaceutical grade azone.

The preparation method of above-mentioned chlorine dioxide sustained-release liquid Band-Aid, comprises the following steps:

Mix isoacetone and butyl acetate, add acrylic acid/N-vinylpyrrolidone hydrogel to it under stirring, then heat up to 60°C to swell completely, then add the remaining raw materials to it, and keep it at 60°C in the dark and keep warm. It was prepared by stirring and reacting for 4h at a rotating speed of 500r/min.

Example 3

A chlorine dioxide sustained-release liquid Band-Aid, comprising the following components by weight: 25 parts of acrylic acid/N-vinylpyrrolidone hydrogel, 24 parts of isopropanol, 12 parts of butyl acetate, 12 parts of amyl acetate, 3 parts of castor oil, 2 parts of tocopheryl acetate, 4 parts of benzyl alcohol, 15 parts of chlorine dioxide, 5 parts of pharmaceutical grade azone.

The preparation method of above-mentioned chlorine dioxide sustained-release liquid Band-Aid, comprises the following steps:

Mix isoacetone and butyl acetate, add acrylic acid/N-vinylpyrrolidone hydrogel to it under stirring condition, then heat up to 40°C to swell completely, then add the remaining raw materials to it, and keep it at 40°C under the condition of keeping away from light and keeping warm. The product was prepared by stirring and reacting for 2h at a rotational speed of 300r/min.

Example 4

A chlorine dioxide sustained-release liquid Band-Aid, comprising the following components by weight: 27 parts of acrylic acid/N-vinylpyrrolidone hydrogel, 36 parts of isopropanol, 12 parts of butyl acetate, 12 parts of amyl acetate, 3 parts of castor oil, 3 parts of tocopheryl acetate, 2 parts of benzyl alcohol, 20 parts of chlorine dioxide, 3 parts of pharmaceutical grade azone.

The preparation method of above-mentioned chlorine dioxide sustained-release liquid Band-Aid, comprises the following steps:

Mix isoacetone and butyl acetate, add acrylic acid/N-vinylpyrrolidone hydrogel to it under stirring conditions, then heat up to 55°C to swell completely, then add the remaining raw materials to it, and keep it at 55°C under the condition of avoiding light and keeping warm. The product was prepared by stirring and reacting for 2h at a rotating speed of 450r/min.

Comparative Example 1

A liquid Band-Aid, comprising the following components in parts by weight: 30 parts of acrylic acid/N-vinylpyrrolidone hydrogel, 30 parts of isopropanol, 8 parts of butyl acetate, 8 parts of amyl acetate, 5 parts of castor oil, fertility 1 part of phenol acetate, 5 parts of benzyl alcohol, 3 parts of pharmaceutical grade azone.

The preparation method is the same as that of Example 2.

Comparative Example 2

A chlorine dioxide sustained-release liquid band-aid, comprising the following components by weight: 30 parts of polyvinylpyrrolidone, 30 parts of isopropanol, 8 parts of butyl acetate, 8 parts of amyl acetate, 5 parts of castor oil, and tocopherol 1 part of acetate, 5 parts of benzyl alcohol, 15 parts of chlorine dioxide, 3 parts of pharmaceutical grade azone.

The preparation method is the same as that of Example 2.

Test example

The liquid band-aids prepared in Examples 1-4 and Comparative Examples 1-2 were respectively tested for performance, and the specific test method was as follows:

(1) Determination of film forming time:

Take about 0.5g of the liquid Band-Aid prepared in Examples 1-4 and pour it on the petri dish, so that it can be spread over the entire watch dish naturally and evenly, with a thickness of about 0.2mm. When the film can be lifted, record the time used; The process is shown in Figure 1.

(2) Membrane mechanical properties test:

Take about 0.5g of the liquid Band-Aid prepared in Examples 1-4, pour it into a petri dish, let it stand for 5 minutes, and make it cast into a film. The cross-sectional area is 30mm×(0.020mm±0.003mm) respectively. The cross-sectional area S (mm ² ) of the membrane. Gently peel off the film, pay attention to make the edge of the cut film smooth without nicks, and clamp both ends in the tensile tester. At this time, the length of the film between the two clamps is recorded as the length before the film test (L ₀ ). The experiment was carried out at a tensile speed of 2.5 mm/min and a load of 500 N. When the film was broken from the center, the breaking force F (N) and the distance L _max (mm) of the clips at both ends were recorded. Then the tensile strength Tensile=F/S, the elongation percentage at break point Elongation=Lmax/L ₀ , and the test results are shown in Table 1.

Table 1 Product film forming time and mechanical properties test data table

(3) Air permeability test:

Using the water vapor transmission rate as the evaluation standard, the mass of water vapor passing through the unit film area per unit time was investigated. Take about 1 g of the sample, cast it into a film, add an appropriate amount of distilled water to a 10 mL vial, cover it with a film and seal it so that the water surface is 5mm±2mm away from the film, place it in a desiccator, and record the weight difference after 24 hours.

M ₀ = weight of initial vial (mg)

M _24h = mass of vial after 24h (mg)

S = bottle mouth area (mm ² )

t = time (h)

The results show that the water vapor transmission rate of the sample in Example 1 can reach 0.7 mg·cm ^-2 ·h within 24 hours; the water vapor transmission rate of the sample in Example 2 can reach 0.8 mg·cm ^-2 within 24 hours h; the water vapor transmission rate of the sample in Example 3 can reach 0.8 mg·cm ^-2 h within 24 hours; the water vapor transmission rate of the sample in Example 4 can reach 0.6 mg·cm ^-2 in 24 hours ·h; the water vapor transmission rate of the sample of Comparative Example 1 within 24 hours was 0.7 mg·cm ^-2 ·h; the water vapor transmission rate of the sample of Comparative Example 2 within 24 hours was 0.6 mg·cm ^-2 ·h.

(4) Waterproof test:

Take about 1.0 g of the liquid Band-Aid prepared in Examples 1-4 respectively, cast to form a film, take a vial with a diameter of 12 mm, add 5 ml of distilled water, cover the vial with the above-mentioned film, invert, after 24 hours. Poor recording quality, water permeability was calculated.

M ₀ = weight of initial vial/g

M _24h = mass/g of vial after 24h

M _w = mass of water in vial/g

The results show that the water permeability of the sample in Example 1 is 1.8% in 24 hours; the water permeability of the sample in Example 2 is 1.7% in 24 hours; the water permeability of the sample in Example 3 is 1.9% in 24 hours The water permeability of the sample in Example 4 is 1.9% at 24 hours, the water permeability of the sample of Comparative Example 1 at 24 hours is 1.8%; the water permeability of the sample of Comparative Example 2 at 24 hours is 2.2%.

(5) Antibacterial test:

Since the film-forming time and mechanical properties of Example 2 are the best among the four implementation cases, the antibacterial test is carried out in Example 2. Dip the bacterial suspensions of Staphylococcus aureus and Pseudomonas aeruginosa respectively with a sterile inoculating loop, spread them evenly on the surface of the medium, and take 10.0 μL of the liquid Band-Aid product prepared in Example 2 on the surface of the above-mentioned medium, at 25° C. Culture in a constant temperature incubator, and observe the antibacterial effect of the product at different times. The specific results are shown in Figure 2.

It can be seen from Figure 2 that the prepared chlorine dioxide sustained-release liquid band-aid has a strong bactericidal effect, and can effectively kill Staphylococcus aureus, Pseudomonas aeruginosa, etc. within 2 minutes, and has a significant antibacterial effect, which can Effectively prevent wound infection.

(6) Slow release effect test:

According to the requirements of the Chinese Pharmacopoeia, a transdermal absorption device was used as the test device for drug release in vitro. The dialysis membrane was first boiled with 1 mmol/L EDTA and 0.2 mmol/L sodium bicarbonate for 15 minutes, washed with distilled water to simulate animal skin, and normal saline was used as the recipient. The medium, combined with UV spectrophotometry to determine the permeation amount of chlorine dioxide per unit area in the drug at different times, taking the time as the abscissa and the cumulative release of the drug as the ordinate, to draw the release curve of the chlorine dioxide sustained-release liquid Band-Aid. The obtained cumulative release-time curve data was subjected to Higuchi equation fitting and regression analysis to determine the sustained-release effect of the chlorine dioxide sustained-release liquid Band-Aid. The specific results are shown in Figure 3 and Table 2.

Table 2 Higuchi equation fitting data table for in vitro release

The in vitro release curve of Examples 1-4 conforms to the Higuchi equation, which proves that the product can effectively realize the sustained release of chlorine dioxide bacteriostatic drugs, and the release process is first fast and then slow, which can ensure that the drug concentration for preventing and treating wound infection in the initial stage of use can be achieved, It can also be released slowly and persistently, prolong the effect, reduce the number of dressing changes, and speed up wound healing.

(7) Hemostatic performance test:

Take 20.0 ml of mouse venous blood, add it into a centrifuge tube containing 2.0 ml of 3.5% sodium citrate solution, mix well, and separate the plasma for 10 min with a centrifugal radius of 7.5 cm and 1000 r/min. Take 0.1ml of the products of Example 2 and Comparative Example 1 and 0.1ml of the above plasma and mix them in a centrifuge tube. After pre-warming in a 37°C water bath for 1min, add 0.1ml of 0.2% CaCl ₂ solution, mix well and start timing. Stop timing when white gums appear, and repeat three times to get the average value. The average in vitro coagulation time of Example 2 was 243±13 seconds, and the average in vitro coagulation time of Comparative Example 1 was 365±9 seconds, that is, the addition of chlorine dioxide helped the wound to coagulate rapidly and played a better protective effect on the wound.

(8) PH sensitivity determination of acrylic acid/N-vinylpyrrolidone interpenetrating network hydrogel:

Use 2mol/L hydrochloric acid and 2mol/L sodium hydroxide to configure the series solutions of PH of 2-12 respectively, take the products of Example 2 and Comparative Example 2 of the same quality respectively, put the gel into the solution and soak it until it is fully swollen to take out. The filter paper wiped off the outer surface of the gel to participate in the solution, and the mass was weighed to calculate the swelling rate. Take the pH value as the abscissa and the swelling rate as the ordinate for comparison, as shown in Figure 4.

G ₁ : mass before swelling/g

G ₂ : mass before swelling/g

Observing the relationship between the swelling ratio and pH of Example 2 and Comparative Example 2, it can be found that in Example 2, due to the use of acrylic acid/N-vinylpyrrolidone interpenetrating network hydrogel, different swelling ratios can be achieved under different pH conditions, thereby controlling the two. The amount of chlorine oxide released, while the swelling rate of the acrylic acid/N-vinylpyrrolidone hydrogel gel in Comparative Example 2 was basically unchanged under different pH conditions, and the pH response could not be achieved.

Claims (10)

1. a chlorine dioxide sustained-release type liquid band-aid, is characterized in that, comprises the component of following weight portion: acrylic acid/N-vinylpyrrolidone hydrogel 20-30 parts, isopropanol 24-36 parts, butyl acetate 8-12 parts of ester, 8-12 parts of amyl acetate, 2-5 parts of castor oil, 0.2-3 parts of tocopheryl acetate, 2-8 parts of benzyl alcohol, 5-20 parts of chlorine dioxide, pharmaceutical grade azone 3-5 servings. 2. chlorine dioxide sustained-release liquid Band-Aid as claimed in claim 1, is characterized in that, comprises the component of following weight portion: acrylic acid/N-vinylpyrrolidone hydrogel 30 parts, isopropanol 30 parts, acetic acid 8 parts of butyl ester, 8 parts of amyl acetate, 5 parts of castor oil, 1 part of tocopheryl acetate, 5 parts of benzyl alcohol, 15 parts of chlorine dioxide, and 3 parts of pharmaceutical grade azone. 3. The chlorine dioxide sustained-release liquid Band-Aid according to claim 1 or 2, wherein the acrylic acid/N-vinylpyrrolidone hydrogel is obtained by the following method: N-vinylpyrrolidone is dissolved in Distilled water, keep for 0.5h, add acrylic monomer and cross-linking agent and initiator while stirring, then react in a sealed water bath environment at 55-65 ℃ for 20-30h, take out the product, soak and wash repeatedly with distilled water, fully purify, be made of. 4. chlorine dioxide sustained-release liquid Band-Aid as claimed in claim 3, is characterized in that, the mass ratio of described N-vinylpyrrolidone and acrylic monomer is 3:1, and the consumption of crosslinking agent is N-ethylene The amount of the initiator is 1.5wt% of the mass of the N-vinylpyrrolidone monomer, and the amount of the initiator is 0.8wt% of the mass of the N-vinylpyrrolidone monomer. 5. chlorine dioxide sustained-release liquid Band-Aid as claimed in claim 3, is characterized in that, described crosslinking agent is N-N' methylenebisacrylamide, and described initiator is potassium persulfate, persulfuric acid Ammonium or azobisisobutyronitrile. 6. The chlorine dioxide sustained-release liquid Band-Aid according to claim 1, further comprising 0.5-2 parts of fragrance essential oil. 7. chlorine dioxide sustained-release liquid Band-Aid as claimed in claim 1, is characterized in that, described fragrant essential oil is lavender essential oil or peppermint essential oil. 8. the preparation method of the chlorine dioxide sustained-release liquid Band-Aid described in any one of claim 1-7, is characterized in that, comprises the following steps: Mix isoacetone and butyl acetate, add acrylic acid/N-vinylpyrrolidone hydrogel to it under stirring condition, then heat up to swelling, add the remaining raw materials to it, and stir and react under the condition of keeping away from light and heat preservation to obtain . 9. The preparation method of chlorine dioxide sustained-release liquid Band-Aid as claimed in claim 8, characterized in that, after being warmed up to 40-60 DEG C until fully swollen, adding remaining raw materials, then under 40-60 DEG C dark conditions The reaction is stirred under the rotating speed of 300r/min--500r/min. 10. The preparation method of chlorine dioxide sustained-release liquid Band-Aid as claimed in claim 8, characterized in that the stirring reaction time is 2-4h under light-proof conditions.

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