Medical liquid dressing capable of forming film and easy to peel and preparation method thereof

Abstract

The invention relates to a medical liquid dressing capable of forming a film and easy to peel and a preparation method thereof.The liquid dressing is prepared from, by mass, 1-20 parts of a modified film-forming agent, 0.01-5 parts of a plasticizer and 62-95 parts of a polar solvent, the modified film-forming agent is polyvinyl alcohol subjected to alkyl hydrophobic modification, and the polar solvent is polyvinyl alcohol subjected to alkyl hydrophobic modification. The plasticizer is a mixture of triethyl citrate and cyclohexane 1, 2-diisononyl diformate, and the plasticizer is a mixture of triethyl citrate and cyclohexane 1, 2-diisononyl diformate. Furthermore, a functional surfactant and micron-sized inorganic particles are respectively added, so that the large-size stripping performance and the air permeability and seepage drainage promoting performance of the liquid dressing can be respectively improved in a targeted manner; and the prepared liquid dressing has good film-forming property, easy stripping property and high air permeability. The wound dressing is applicable to protection of various wounds, and can prevent infection and promote wound healing while protecting the wounds. The liquid dressing disclosed by the invention is simple in composition, universal in preparation method and low in cost, and also has a good application prospect in other biomedical fields.

Description

Technical Field

[0001] The present invention relates to the field of biomaterials, and particularly to a medical liquid dressing that can form a film and is easily peeled off, and a preparation method thereof. Background Art

[0002] Traditional wound plasters are mainly composed of an absorbent pad and an adhesive tape, and are suitable for most superficial wounds, especially flat and dry parts, such as the arms and legs. Liquid dressings form a protective film on the wound surface to isolate external pollutants and bacteria, and are particularly suitable for wounds with small areas, irregular shapes or joint parts, such as frequently moving parts like fingers and knees. Compared with traditional wound plasters, the advantages of liquid dressings are that they are transparent, do not affect the appearance, are not easily detached and have good water resistance, can cover wounds with irregular shapes, have high flexibility, and reduce pain.

[0003] During use, the protective film formed in situ by the liquid dressing will form a mechanically interlocked interfacial force with the skin and the surface of the irregular wound, which will cause incomplete peeling during the removal process and hinder wound healing; at the same time, due to the strong interfacial force during the removal process, it will also cause tearing of the wound surface and bring secondary injuries, especially for larger-sized wounds. In addition, after the liquid dressing forms a film, there are gaps between the molecular chains of the polymer material, and gas molecules can move in these gaps, thereby achieving a certain degree of breathability. This means that its breathability is mainly achieved through molecular diffusion, that is, the concentration gradient of gas molecules diffuses from the high-concentration side to the low-concentration side. The generation of wounds, especially large-sized wounds, is often accompanied by liquid exudation. If the exudate is not volatilized in time, after a large amount of it is generated, it will accumulate between the protective film and the skin. With the movement of the wound surface, the accumulated exudate will inevitably rupture and cause infection.

[0004] On this basis, the present invention has developed a medical liquid dressing that can form a film and is easily peeled off based on polyvinyl alcohol. Through component screening and matching, it is regulated that the liquid dressing can not only have the characteristics of rapid film formation, air permeability and water resistance, but also has an appropriate adhesion strength with tissues after film formation and strong peelability, and can achieve painless, residue-free and complete removal of the protective film. Summary of the Invention

[0005] Aiming at the problems existing in the prior art, the present invention provides a medical liquid dressing that can form a film and is easily peeled off and its preparation. After the liquid dressing is applied to the wound and the surrounding skin, it can quickly form a colorless and transparent film. The film closely adheres to the surface to protect the wound surface, does not swell in water, has waterproofness, comfort and breathability, and at the same time has excellent peelability. When the film is not needed, it can be completely removed along the edge of the film without pain.

[0006] To solve the above problems, the present invention adopts the following technical solutions: A medical liquid dressing that can form a film and is easily peelable, by mass fraction, comprises the following components: 1-20 parts of a modified film-forming agent, 0.01-5 parts of a plasticizer, and 62-95 parts of a polar solvent. The modified film-forming agent is polyvinyl alcohol modified by alkyl hydrophobic modification, and the plasticizer is a mixture of triethyl citrate and diisononyl cyclohexane-1,2-dicarboxylate.

[0007] In the above technical solution, further, the modification process of the modified film-forming agent includes the dissolution, alkyl modification, and purification of polyvinyl alcohol. By mass fraction, 1-20 parts of polyvinyl alcohol are added to 60-80 parts of a mixed solvent for dissolution, then an acid and 1-20 parts of a hydrophobic modifier are added, and the reaction is carried out for 6-48 h, and it is obtained after purification with ice ethanol. The mixed solvent is a mixture of dimethyl sulfoxide and water, wherein there are 30-40 parts of dimethyl sulfoxide and 30-40 parts of water.

[0008] Further, the hydrophobic modifier is CH3(CH2)nCHO, where n is 1-9. The molecular weight of the polyvinyl alcohol is usually 20000-1000000.

[0009] Further, the temperature of the reaction is 30-100 °C, and the acid is at least one of hydrochloric acid, sulfuric acid, acetic acid, phosphoric acid, and oxalic acid, and the acidity of the system is controlled at 0.1%-10%.

[0010] Further, the polar solvent is one or more of absolute ethanol, ethyl acetate, methanol, and butyl acetate.

[0011] Further, the mass ratio of triethyl citrate to diisononyl cyclohexane-1,2-dicarboxylate in the plasticizer is 0.5-4.

[0012] Further, the liquid dressing also contains 0.01-3 parts of a functional surfactant.

[0013] Further, the functional surfactant is one or more of linear polylysine, branched polylysine, and lysine polymer derivatives.

[0014] Further, the liquid dressing also contains 0.01-10 parts of micron-sized inorganic particles.

[0015] Further, the micron-sized inorganic particles are one or more of titanium dioxide, calcium carbonate, alumina, and silica.

[0016] The preparation method of the medical liquid dressing that can form a film and is easily peelable according to the present invention is to dissolve the modified film-forming agent in the polar solvent, then add the plasticizer, or further, add the functional surfactant and / or micron-sized inorganic particles, and stir evenly.

[0017] The term "film-forming" means that the liquid dressing can automatically form a transparent, breathable and water-blocking protective film on the application surface after application. The term "easy to peel off" means that the formed protective film can be completely removed without causing adhesion or tearing to the wound surface, resulting in secondary injury, and can be peeled off without pain, residue and integrity.

[0018] The beneficial effects of the present invention are as follows: By hydrophobically modifying polyvinyl alcohol and introducing a specific compound plasticizer into the system, the present invention prepares a liquid dressing that can quickly form a film on the wound surface, and the obtained protective film has the characteristics of water-blocking, breathability, comfort and painless and complete peeling. Especially after adding a functional surfactant, the surface tension of the liquid dressing after application can be further reduced, which is more conducive to the formation of a large-size and uniform protective film layer, and can be better used for large-size wound surfaces. However, the exudation problem faced by large-size wound surfaces is relatively more serious. By introducing micron-sized inorganic particles on the basis of the liquid dressing, the formed protective film can greatly improve the breathability of the protective film while maintaining the above-mentioned characteristics, which is more helpful for the discharge of exudate and the acceleration of wound healing. The liquid dressing of the present invention has more excellent easy-to-peel and breathable and penetration-promoting properties compared with the prior art, and is especially suitable for the protection of large wounds. Brief Description of the Drawings

[0019] Figure 1 It is a schematic diagram of the modification method of the modified film-forming agent in the present invention; Figure 2 It is the film-forming and peeling effect between the liquid dressing prepared in Example 11 of the present invention and the simulated skin (release paper), and it is a measured diagram of taking 5 mL of the liquid dressing and evenly smearing it on an area of about 15 cm * 15 cm on the release paper; Figure 3 It is the film-forming and peeling effect between the liquid dressings prepared in Examples 4 (C3), 5 (C0), and 6 (C10) of the present invention and the skin, and it is a measured diagram of taking 2-3 drops (about 0.1-0.15 mL) of the liquid dressing and evenly smearing it on an area of about 2 cm * 3 cm on the back of the hand; Figure 4 It is a comparison diagram of the water vapor transmission rate of the liquid dressings prepared in Example 9 and Example 10 of the present invention after film formation; Figure 5 It is the effect diagram of the liquid dressing prepared in Example 9 of the present invention applied to the wound surface of rats. Detailed Embodiments

[0020] The following further illustrates the technical solutions of the present invention in conjunction with embodiments, but these embodiments do not limit the present invention. Unless otherwise specified, the "parts" are all by mass.

[0021] The preparation method of the modified polyvinyl alcohol in the embodiments of the present invention is as follows: Take 15 parts of polyvinyl alcohol with a molecular weight of 80,000 and disperse it in 80 parts of a mixed solvent (40 parts of water and 40 parts of dimethyl sulfoxide). Dissolve it at 80 °C for 5 hours, then add 1 part of a hydrophobic modifier and 1 part of 6 mol / L hydrochloric acid, and react at 60 °C for 10 h. Put the obtained sample into a dialysis bag with a molecular weight cut-off of 3500 and dialyze for 5 days, then dry to obtain modified polyvinyl alcohol. In the present invention, the hydrophobic modifier is preferably CH3(CH2)nCHO, where n is 1-9.

[0022] In the examples of the present invention, the obtained liquid dressing is evenly coated on the release paper. After it volatilizes and forms a film, the prepared film is subjected to water resistance, bacteriostasis, air permeability, comfort, and antibacterial performance tests for 4 h according to the standards of YY / T 0471.3-2004, YY / T 0471.5-2017, YY / T 0471.2-2004, YY / T 0471.4-2004, and WS / T 650-2019 5.2.6 to investigate the performance of the formed protective film. Among them, the air permeability is tested by uniformly coating the liquid dressing on the surface of polytetrafluoroethylene, and after drying, tearing it off and referring to YY / T 0471.2-2004 for testing the water vapor transmission rate; In the examples of the present invention, the obtained liquid dressing is dropped on a small-sized artificial skin of 2 cm * 3 cm, and after drying, the adhesion state between the film and the skin is tested; the size of the artificial skin is replaced with 15 cm * 15 cm to investigate the peeling effect of the large-sized film. The volume of the liquid dressing applied on the artificial skin per unit area is equal in the small-sized and large-sized tests.

[0023] Example 1

[0024] Take 8 parts of the modified polyvinyl alcohol sample (the hydrophobic modifier is butyraldehyde (C4)) and dissolve it in 95 parts of absolute ethanol. Add 0.3 parts of diisononyl cyclohexane-1,2-dicarboxylate and 0.1 part of triethyl citrate, and stir for 10 hours to obtain a liquid dressing. After testing, the liquid dressing can quickly form a film within 1 minute. The obtained film has good comfort (stretchability of 0.2 N / cm and permanent deformation rate less than 1%), water resistance (test result according to the standard: passed), bacteriostasis (test result according to the standard: passed), air permeability (1385 g m -2 d -1 ); it can be completely peeled off from the small-sized artificial skin of 2 cm * 3 cm without damage to the film, and it can be peeled off from the large-sized artificial skin of 15 cm * 15 cm, but there is some residue.

[0025] Example 2

[0026] Take 8 parts of modified polyvinyl alcohol samples (the hydrophobic modifier is butyraldehyde (C4)) and dissolve them in 95 parts of absolute ethanol. Add 0.3 part of diisononyl cyclohexane-1,2-dicarboxylate and stir for 10 hours to obtain a liquid dressing. After testing, the liquid dressing can form a film rapidly within 1 minute. The obtained film has water resistance and antibacterial property, but poor comfort (stretchability 0.7 N / cm, permanent deformation rate greater than 5%).

[0027] Example 3

[0028] Take 8 parts of modified polyvinyl alcohol samples (the hydrophobic modifier is butyraldehyde (C4)) and dissolve them in 95 parts of absolute ethanol. Add 0.1 part of triethyl citrate and stir for 10 hours to obtain a liquid dressing. After testing, the obtained film cannot be completely peeled off on both the small-sized simulated skin of 2 cm * 3 cm and the 15 cm * 15 cm simulated skin.

[0029] Example 4

[0030] Take 8 parts of modified polyvinyl alcohol samples (the hydrophobic modifier is propionaldehyde (C3)) and dissolve them in 95 parts of absolute ethanol. Add 0.3 part of diisononyl cyclohexane-1,2-dicarboxylate and 0.1 part of triethyl citrate and stir for 10 hours to obtain a liquid dressing. After testing, the liquid dressing can form a film rapidly within 1 minute. The obtained film has good comfort (stretchability 0.1 N / cm, permanent deformation rate less than 1%), water resistance (test result according to the standard: passed), antibacterial property (test result according to the standard: passed), and air permeability (1313 g m -2 d -1 );It can be completely peeled off on the small-sized simulated skin of 2 cm * 3 cm, and the film is not damaged. When peeling the film on the large-sized simulated skin of 15 cm * 15 cm, the film is damaged and remains, and cannot be completely removed.

[0031] Example 5

[0032] Take 8 parts of polyvinyl alcohol (unmodified) and dissolve them in a mixed solution of 95 parts of ethanol and water (volume ratio 1:1). Add 0.3 part of diisononyl cyclohexane-1,2-dicarboxylate and 0.1 part of triethyl citrate and stir for 10 hours to obtain a liquid dressing. After testing, the film-forming time of the liquid dressing is about 5 minutes, and the water resistance test fails 24 hours after film formation. It cannot be completely peeled off on the small-sized simulated skin of 2 cm * 3 cm after film formation and is easily damaged.

[0033] Example 6

[0034] Take 8 parts of modified polyvinyl alcohol samples (the hydrophobic modifier is decanal (C10)) and dissolve them in 95 parts of absolute ethanol. Add 0.3 parts of diisononyl cyclohexane-1,2-dicarboxylate and 0.1 part of triethyl citrate, and stir for 10 hours to obtain a liquid dressing. After the obtained liquid dressing forms a film, warping will occur. After forming a film, it cannot be completely peeled off on both small-sized simulated skins of 2 cm * 3 cm and large-sized simulated skins of 15 cm * 15 cm, and there is residual adhesion.

[0035] Example 7

[0036] Take 8 parts of modified polyvinyl alcohol samples (the hydrophobic modifier is propionaldehyde (C3)) and dissolve them in 95 parts of absolute ethanol. Add 0.3 parts of glycerol and 0.1 part of triethyl citrate, and stir for 10 hours to obtain a liquid dressing. After forming a film, the obtained film can be peeled off on small-sized simulated skins of 2 cm * 3 cm and simulated skins of 15 cm * 15 cm, but the poor adhesion of the film on the skin surface causes it to fall off easily, and on-demand peeling cannot be achieved.

[0037] Example 8

[0038] Take 8 parts of modified polyvinyl alcohol samples (the hydrophobic modifier is propionaldehyde (C3)) and dissolve them in 95 parts of absolute ethanol. Add 0.3 parts of dibutyl phthalate and 0.1 part of glycerol, and stir for 10 hours to obtain a liquid dressing. After forming a film, the obtained film can be peeled off on small-sized simulated skins of 2 cm * 3 cm and simulated skins of 15 cm * 15 cm, but the poor adhesion of the film on the skin surface causes it to fall off easily, and on-demand peeling cannot be achieved.

[0039] Example 9

[0040] Take 8 parts of modified polyvinyl alcohol samples (the hydrophobic modifier is propionaldehyde (C3)) and dissolve them in 95 parts of absolute ethanol. Add 0.3 parts of diisononyl cyclohexane-1,2-dicarboxylate, 0.1 part of triethyl citrate, and 0.2 parts of polylysine, and stir for 10 hours to obtain a liquid dressing. After testing, the obtained film has water resistance (test result according to the standard: passed), antibacterial property (test result according to the standard: passed), air permeability (1520 g m -2 d -1 ), good comfort (stretchability 0.1 N / cm, permanent deformation rate < 1%), and can be completely peeled off on both small-sized simulated skins of 2 cm * 3 cm and large-sized simulated skins of 15 cm * 15 cm. Such as Figure 5As shown (scale in the figure is 1 cm), when the liquid dressing was used on the abrasion and incision wounds of rats, it could be seen that the film could be peeled off on the 0th and 1st days. The abrasion basically recovered on the 5th day, and the incision also basically recovered on the 7th day. Before and after adding polylysine, the surface tension of the liquid dressing changed. By adding polylysine, the surface tension of the liquid dressing could be effectively reduced (18.58 mN / m), and the surface tension of the solution without adding polylysine was 36.79 mN / m. At the same time, it was found that the dosage of polylysine could not be too much. When more than 3 parts of polylysine were added, it could not be completely dissolved in the system, and a transparent and uniform liquid form could not be formed, which would affect the film-forming uniformity and use effect of the liquid dressing. In addition, the structural form of polylysine had little effect on the performance of the liquid dressing. Whether it was linear polylysine, branched polylysine or polylysine derivatives, they all had similar effects, and they were collectively referred to as functional surfactants in the present invention.

[0041] Example 10

[0042] 8 parts of modified polyvinyl alcohol samples (the hydrophobic modifier was propionaldehyde (C3)) were dissolved in 95 parts of absolute ethanol, and 0.3 parts of diisononyl cyclohexane-1,2-dicarboxylate, 0.1 part of triethyl citrate, 0.2 part of polylysine, and 0.1 part of calcium carbonate were added. After stirring for 10 hours, a liquid dressing was obtained. After testing, the obtained film had water resistance (test result according to the standard: passed), antibacterial property (test result according to the standard: passed), air permeability (2735 g m -2 d -1 ), good comfort (stretchability 0.1 N / cm, permanent deformation rate < 1%), and could be completely peeled off on both small-sized simulated skin of 2 cm * 3 cm and large-sized simulated skin of 15 cm * 15 cm. It could be seen that the water vapor transmission rate of the film obtained in this example was significantly higher than that of the liquid dressing film prepared in Example 9 (1520 g m -2 d -1 ), and it was more conducive to being applied to large-sized wounds prone to exudate.

[0043] Example 11

[0044] 8 parts of modified polyvinyl alcohol samples (the hydrophobic modifier was butyraldehyde (C4)) were weighed and dissolved in 70 parts of absolute ethanol, and 0.3 parts of diisononyl cyclohexane-1,2-dicarboxylate, 0.1 part of triethyl citrate, 0.05 part of silicon dioxide, and 0.2 part of hyperbranched polylysine were added. After stirring for 10 hours, a liquid dressing was obtained.

[0045] As Figure 2As shown, the liquid dressing is evenly coated on the release paper and forms a film after evaporating for one minute. The obtained film can be completely peeled off. The prepared film is respectively tested for water resistance, bacteriostasis, air permeability, comfort and antibacterial performance for 4 h according to the standards of YY / T 0471.3-2004, YY / T 0471.5-2017, YY / T 0471.2-2004, YY / T 0471.4-2004 and WS / T 650-2019 5.2.6. The liquid dressing in this example has excellent comprehensive performance after forming a film. The obtained film has water resistance (test result according to the standard: passed), bacteriostasis (test result according to the standard: passed), air permeability (2833 gm -2 d -1 ), good comfort (stretchability 0.2 N / cm, permanent deformation rate < 1%), and can be completely peeled off on both small-sized simulated skin of 2 cm * 3 cm and large-sized simulated skin of 15 cm * 15 cm.

[0046] The above embodiments are only some preferred solutions of the present invention, but they are not intended to limit the present invention. Those of ordinary skill in the relevant technical fields can still make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, all technical solutions obtained by adopting the means of equivalent replacement or equivalent transformation fall within the protection scope of the present invention.

Claims

1. A medical liquid dressing that can form a film and is easily peeled off, characterized in that, By mass parts, it includes the following components: 1 - 20 parts of modified film-forming agent, 0.01 - 5 parts of plasticizer, and 62 - 95 parts of polar solvent. The modified film-forming agent is polyvinyl alcohol modified by alkyl hydrophobic modification, and the plasticizer is a mixture of triethyl citrate and diisononyl cyclohexane-1,2-dicarboxylate.

2. The film-forming and easily peelable medical liquid dressing according to claim 1, wherein The modification process of the modified film-forming agent includes the dissolution, alkyl modification, and purification of polyvinyl alcohol. By mass parts, 1 - 20 parts of polyvinyl alcohol are added to 60 - 80 parts of a mixed solvent for dissolution, then an acid and 1 - 20 parts of a hydrophobic modifier are added, and the reaction is carried out for 6 - 48 h. After purification with ice ethanol, it is obtained. The mixed solvent is a mixture of dimethyl sulfoxide and water, where 30 - 40 parts of dimethyl sulfoxide and 30 - 40 parts of water.

3. The medical liquid dressing capable of forming a film and being easily peeled off according to claim 2, wherein The hydrophobic modifier is CH3(CH2)nCHO, where n is 1 - 9.

4. The medical liquid dressing capable of forming a film and being easily peeled off according to claim 2, wherein The temperature of the reaction is 30 - 100 °C, and the acid is at least one of hydrochloric acid, sulfuric acid, acetic acid, phosphoric acid, and oxalic acid, controlling the acidity of the system at 0.1% - 10%.

5. The film-forming and easily peelable medical liquid dressing according to claim 1, characterized in that, The polar solvent is one or more of absolute ethanol, ethyl acetate, methanol, and butyl acetate.

6. The medical liquid dressing capable of forming a film and being easily peeled off according to claim 1, wherein The mass ratio of triethyl citrate and diisononyl cyclohexane-1,2-dicarboxylate in the plasticizer is 0.5 - 4.

7. The medical liquid dressing capable of forming a film and being easily peeled off according to claim 1, wherein The liquid dressing also contains 0.01 - 3 parts of functional surfactant.

8. The medical liquid dressing capable of forming a film and being easily peeled off according to claim 1, wherein The functional surfactant is one or more of linear polylysine, branched polylysine, and lysine polymer derivatives.

9. The medical liquid dressing capable of forming a film and being easily peeled off according to claim 1, wherein The liquid dressing also contains 0.01 - 10 parts of micron-sized inorganic particles.

10. The medical liquid dressing capable of forming a film and being easily peeled off according to claim 1, wherein, The micron-sized inorganic particles are one or more of titanium dioxide, calcium carbonate, alumina, and silica.

Images