CN112741105A

CN112741105A - Solution with high antimicrobial and lubricating effects

Info

Publication number: CN112741105A
Application number: CN201911041587.XA
Authority: CN
Inventors: 吕倩如; 刘佩宜; 江沅庭; 张菀芯; 林代恩; 林旻萱
Original assignee: Yongsheng Optics Co ltd
Current assignee: Yongsheng Optics Co ltd
Priority date: 2019-10-30
Filing date: 2019-10-30
Publication date: 2021-05-04

Abstract

A solution with high antimicrobial and lubricating effects comprises antimicrobial component and lubricating component, wherein the concentration of the antimicrobial component is 1-3000 ppm. Greater than 90% of the microorganisms are killed when the concentration of the antimicrobial component in the solution is at least 1ppm and the solution contacts the target for at least 300 seconds. Greater than 90% of the microorganisms are killed when the concentration of the antimicrobial component in the solution is at least 10ppm and the solution is in contact with the target for at least 10 seconds.

Description

Solution with high antimicrobial and lubricating effects

Technical Field

The present invention relates to a solution having high antimicrobial activity and lubricating effect, and more particularly, to a solution having high antimicrobial activity and lubricating effect, which has an antimicrobial component concentration of at least 1 ppm/10 ppm and can kill more than 90% of microorganisms for a target contact time of at least 300 seconds/10 seconds.

Background

In the contact lens market, how to effectively disinfect the lenses and maintain the lubricity of the lenses are two important issues. Conventionally, as the lubricant component to be added to the contact lens solution, a polyhydric alcohol, glycosaminoglycan, cellulose mixed ether, sodium carboxymethylcellulose, carboxymethylcellulose (CMC), Hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), propylene glycol, glycerin, hyaluronic acid, ethyl lactate, an oily substance, or the like is mainly used. When present alone, the lack of antimicrobial components makes the lubricant more susceptible to microbial contamination, which can lead to infection of the user's eyes. However, most of the lubricating ingredients are difficult to be compatible with the bactericidal ingredient, and when the lubricating ingredients and the bactericidal ingredient are mixed at the same time, there is a common problem that the bactericidal ingredient is disturbed by the lubricating ingredient, resulting in a decrease in bactericidal efficacy.

Furthermore, users place importance on safety and antimicrobial efficacy in addition to the disinfection level of contact lenses. One of the contact lens disinfecting solutions is benzalkonium chloride (BAC), which is an antimicrobial component. Benzalkonium chloride has toxicity and irritation although having antimicrobial effect, and is easy to cause corneal injury and pathological changes if a user uses the benzalkonium chloride for a long time. One of the contact lens disinfecting solutions contains polyhexamethylene biguanidine (PHMB) as an antimicrobial component. Polyhexamethylene biguanide has low toxicity, but if it is intended to have a sufficient effect of killing microorganisms in a short time, its concentration needs to be at least 500 ppm, and there is a problem that it is liable to remain. One of the disinfection solutions for contact lenses is hydrogen peroxide as an antimicrobial component, and the disinfection solution can take 4-8 hours to completely convert hydrogen peroxide into oxygen and water through platinum in the antimicrobial process, so as to prevent the unconverted hydrogen peroxide from causing irritation to human eyes. Other types of disinfecting solutions for contact lenses, such as povidone-iodine (PVP-I), chlorhexidine, require concentrations of at least 250ppm, 1000 ppm to provide adequate microbial kill, but the concentration of antimicrobial components can be undesirably reduced for the user.

Disclosure of Invention

The present invention is directed to solving the above technical problems, and embodiments of the present invention provide a solution having high antimicrobial ability and lubricating effect by a specific ratio composition of an antimicrobial component and a lubricating component, and the solution can kill more than 90% of microorganisms after the solution contacts a target for at least a specific time.

Based on at least one of the above objects, the present invention provides a solution having high antimicrobial activity and lubricating effect. The solution comprises an antimicrobial component and a lubricating component, wherein the concentration of the antimicrobial component is from 1 to 3000ppm and the antimicrobial capacity of the solution is: at a concentration of the antimicrobial component of at least 1ppm, the solution kills greater than 90% of the microorganisms when contacted with the target for at least 300 seconds; or the antimicrobial component is at a concentration of at least 10ppm, the solution kills greater than 90% of the microorganisms when contacted with the target for at least 10 seconds.

Optionally, the microorganism is a bacterium, a fungus, or a virus.

Optionally, the concentration of the lubricious component is from 0.01 to 30 milligrams per milliliter (mg/ml).

In accordance with at least one of the above objects, the present invention provides a solution comprising chlorine dioxide and a lubricant component, wherein the concentration of chlorine dioxide is 1-3000ppm and the concentration of the lubricant component is 0.01-30mg/ml, and having high antimicrobial activity and lubricating effect.

Optionally, the lubricating composition comprises at least one of a polyol, a salt of a polyol, a glycosaminoglycan, a salt of a glycosaminoglycan, a cellulose mixed ether, and a salt of a cellulose mixed ether.

Optionally, in the case where the lubricating ingredient is a polyol and/or a salt thereof, the concentration of the polyol and/or the salt thereof is 0.4 to 30 mg/ml; in the case that the lubricating component is glycosaminoglycan and/or its salt, the concentration of glycosaminoglycan and its salt is 0.01-5 mg/ml; and in the case that the lubricating component is cellulose mixed ether and/or salts thereof, the concentration of the cellulose mixed ether and the salts thereof is 0.24 to 10 mg/ml.

Optionally, in the case where the lubricating ingredient is a polyol and/or a salt thereof, the concentration of the polyol and/or the salt thereof is 10 to 30 mg/ml; in the case that the lubricating component is glycosaminoglycan and/or its salt, the concentration of glycosaminoglycan and/or its salt is 0.05-5 mg/ml; and in the case that the lubricating component is cellulose mixed ether and/or salts thereof, the concentration of the cellulose mixed ether and/or salts thereof is 1.2-10 mg/ml.

Alternatively, any of the foregoing solutions, wherein the polyol is glycerol, propylene glycol, octanediol, ethylhexylglycerin, hexylene glycol, xylitol, polyethylene glycol, polypropylene glycol, or pentanediol.

Alternatively, any of the foregoing solutions, wherein the glycosaminoglycan is Hyaluronic Acid (HA), Chondroitin Sulfate (CS), Dermatan Sulfate (DS), Keratan Sulfate (KS), Heparan Sulfate (HS), or Heparin (HP).

Alternatively, any of the foregoing solutions, wherein the cellulose mixed ether is methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, carboxymethyl cellulose, or hydroxyethyl cellulose.

In short, the solution provided by the embodiment of the invention has high-efficiency antimicrobial capacity and lubricating effect. The solutions have low concentrations of antimicrobial components and are therefore very low in harm to the user when used on biomedical materials, such as contact lenses. Moreover, the solution can kill more than 90% of microorganisms in a short time, and has the advantage of high antimicrobial efficiency. The dual-effect of the solution has advantages in various markets where it is needed (e.g., contact lens care solutions, lubricants for sterile machines, etc.).

Drawings

FIG. 1 is a graph of propylene glycol concentration versus coefficient of friction for example 6 of the present invention.

FIG. 2 is a graph of glycerol concentration versus coefficient of friction for example 7 of the present invention.

FIG. 3 is a graph showing the relationship between the concentration of hyaluronic acid and the friction coefficient in example 8 of the present invention.

FIG. 4 is a graph of hydroxypropyl methylcellulose concentration versus coefficient of friction for example 9 of the present invention.

Detailed Description

The following detailed description of the embodiments of the invention refers to the accompanying drawings.

The embodiment of the invention provides a solution with high-efficiency antimicrobial capacity and lubricating effect, which comprises an antimicrobial component and a lubricating component. The antimicrobial component of the solution is selected from chlorine dioxide, and when the concentration of the antimicrobial component is at least 1ppm, the solution kills more than 90% of the microorganisms after 300 seconds of contact with the target; or when the concentration of the antimicrobial component is at least 10ppm, the solution kills more than 90% of the microorganisms after 10 seconds of contact with the target. It should be noted that although the antimicrobial component is selected from chlorine dioxide, the invention is not limited to antimicrobial components, and other antimicrobial components having the antimicrobial ability may be used.

The antimicrobial component "chlorine dioxide" of the solution of the present invention is characterized by a strong oxidizing agent, which is used to combat microorganisms by breaking bonds and inactivating amino acids of the microorganisms, so that the microorganisms eventually die because they are not metabolized. Chlorine dioxide is listed as a safe and efficient disinfectant of A1 grade by the World Health Organization (WHO), and is not easy to cause harm to human bodies even if a small amount of chlorine dioxide is eaten by mistake. Furthermore, chlorine dioxide has the characteristic of being decomposed when exposed to light, namely, after being irradiated by light, the chlorine dioxide is automatically decomposed into oxygen and chloride ions which are harmless to human bodies over time, so that the harm degree is lower along with the longer the using time is. See table 1 for the decomposition of chlorine dioxide. Table 1 shows the tendency of concentration of 1ppm chlorine dioxide aqueous solution under xenon lamp irradiation. Xenon lamps are used to simulate the exposure to sunlight, and are available as UHAO, YS 03. The chlorine dioxide concentration measurement instrument is model number DT1B available from Photometer. As shown in table 1, the detected chlorine dioxide concentration is lower as the xenon lamp irradiation time of the chlorine dioxide aqueous solution is longer, and the chlorine dioxide concentration can be reduced to the concentration (lower than 0.02 ppm) of the lowest detection limit of the detection instrument after the xenon lamp irradiation of the chlorine dioxide aqueous solution for 120 minutes.

TABLE 1

Xenon lamp exposure time (minutes)	Chlorine dioxide concentration (ppm)
		0	1.01
5	0.745
		10	0.56
15	0.385
		30	0.09
60	0.025
		120	Below the detection limit
180	Below the detection limit

Furthermore, the method of introducing chlorine dioxide into the solution of the present invention employs a One-step system, i.e., chlorine dioxide is added directly to the solution in the form of tablets, aqueous solutions, or other forms. The One-step system has the advantages of convenience and safety, and can be used to replace the risks and hazards (e.g., generation of carcinogenic byproducts such as halocarbons, chloramines, and bromates) that may be generated by conventional Two-step (Two-step) systems, in which sodium chlorite is used to react with hydrochloric acid to generate chlorine dioxide. The conventional Two-step system has an advantage of reducing a high loss rate of chlorine dioxide due to easy and rapid dissipation of chlorine dioxide into the air, but since the solution of the present invention can achieve the effect of killing microorganisms in a short time (e.g., 300 seconds), a more convenient and safe One-step system can be used without worrying about the rapid dissipation of chlorine dioxide.

Next, the conditions and effects of the solution having high antimicrobial ability and lubricating effect will be further described through examples. First, please refer to table 2 to know the effect of killing microorganisms of a solution containing only chlorine dioxide, and table 2 is a table of the concentration of chlorine dioxide and the time for killing microorganisms. As shown in Table 2, the antimicrobial component in the solution was chlorine dioxide, which had an antimicrobial effect at a chlorine dioxide concentration of 1 to 3000 ppm. Examples 1 and 2 both used chlorine dioxide at a concentration of 1ppm and each tested at 600/300 seconds for killing microorganisms, and examples 3-5 used chlorine dioxide at a concentration of 3/10/3000 ppm and each tested at 60/10/10 seconds for killing microorganisms, such as but not limited to bacteria, fungi, or viruses. The results of examples 1 to 5 show that the conditions of examples 1 to 5 are effective in killing microorganisms. The results of comparison of examples 1 and 2 show that chlorine dioxide solution with a concentration of 1ppm takes only 300 seconds to have an acceptable microorganism killing effect, and the results of examples 4 and 5 show that chlorine dioxide solution with a concentration of 10ppm takes only 10 seconds to have an acceptable microorganism killing effect, wherein the higher the chlorine dioxide addition concentration, the shorter the time the microorganism can be killed, i.e. the chlorine dioxide addition concentration is proportional to the microorganism killing effect. In the present examples, a satisfactory microbicidal effect is defined as a microbicidal effect of greater than 90%. In the present embodiment, the microorganisms to be tested are bacteria and fungi, and in addition, 2 ppm of chlorine dioxide can kill 93.7% of viruses within 120 seconds, and the conditions fall between the preferred embodiments 2 and 4, so the solution of the present invention can be used for killing bacteria, fungi or viruses.

TABLE 2

Examples	Time (seconds) for killing microorganism	Chlorine dioxide concentration (ppm)	Result of killing microorganism
				1	600	1	Qualified
2	300	1	Qualified
				3	60	3	Qualified
4	10	10	Qualified
				5	10	3000	Qualified

Next, please continue to refer to the following examples to understand the conditions and effects of the solution including both the antimicrobial and the lubricious components. The lubricating component of the solution of the present invention may be a polyol such as, but not limited to, glycerol, propylene glycol, octanediol, ethylhexylglycerin, hexylene glycol, xylitol, polyethylene glycol, polypropylene glycol, or pentanediol, a salt of a polyol such as, but not limited to, glycerol, propylene glycol, octanediol, ethylhexylglycerin, hexylene glycol, xylitol, polyethylene glycol, polypropylene glycol, or pentanediol, a glycosaminoglycan such as, but not limited to, Hyaluronic Acid (HA), Chondroitin Sulfate (CS), Dermatan Sulfate (DS), Keratan Sulfate (KS), Heparan Sulfate (HS), or Heparin (HP), and a cellulose mixed ether such as, but not limited to, methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, carboxymethyl cellulose, or hydroxyethyl cellulose.

Table 3 shows the compatibility test of the lubricant components with chlorine dioxide, wherein in example 6, polyol was used as the lubricant component and propylene glycol was used, in example 7, polyol was used as the lubricant component and glycerin was used, in example 8, glycosaminoglycan was used as the lubricant component and hyaluronic acid (i.e., hyaluronic acid) was used, and in example 9, cellulose mixed ether was used as the lubricant component and hydroxypropylmethylcellulose was used. As shown in Table 3, in examples 6 to 9, in the case where the concentrations of chlorine dioxide were all 1ppm, the concentrations of the lubricating ingredients in examples 6 to 9 were 30mg/ml (mg/ml) of propylene glycol, respectively; glycerol 30 mg/ml; hyaluronic acid 5 mg/ml; the results of examples 6-9 all show acceptable microbial kill at 10 mg/ml hydroxypropyl methylcellulose. The results of examples 6-9 show that the present invention provides solutions wherein the specific combination of antimicrobial and lubricating ingredients maintains antimicrobial efficacy and only low concentrations of the antimicrobial ingredients are required to achieve efficacy.

TABLE 3

Examples	Lubricating composition	Concentration of lubricating ingredients (mg/ml)	Chlorine dioxide concentration (ppm)	Result of killing microorganism
					6	Propylene glycol	30	1	Qualified
7	Glycerol	30	1	Qualified
					8	Hyaluronic acid	5	1	Qualified
9	Hydroxypropyl methylcellulose	10	1	Qualified

When the antimicrobial component is mixed with the lubricating component to form a solution, the concentration of the lubricating component is not limiting. When the lubricating composition is added to a certain concentration, the viscosity of the solution will rise rapidly and will cause its coefficient of friction (COF) to rise. The coefficient of friction is related to the friction between the two surfaces, and the smaller the coefficient of friction of the solution, the more comfortable the user can use the solution, i.e. the smaller the coefficient of friction is. On the contrary, when the friction coefficient of the solution is increased, it causes a user's comfort in use to be lowered and inconvenience to use. Examples 6-9 the respective sets of solutions were also tested for changes in coefficient of friction with the lubricant composition and its concentration and tested as a control with a coefficient of friction of 0.0184 on a model CETR UMT-2 lubricant available from Bruker. Referring to fig. 1 to 4, fig. 1 is a graph showing the relationship between the concentration of propylene glycol and the friction coefficient in example 6 of the present invention, fig. 2 is a graph showing the relationship between the concentration of glycerin and the friction coefficient in example 7 of the present invention, fig. 3 is a graph showing the relationship between the concentration of hyaluronic acid and the friction coefficient in example 8 of the present invention, and fig. 4 is a graph showing the relationship between the concentration of hydroxypropyl methylcellulose and the friction coefficient in example 9 of the present invention. Please refer to the results of examples 6-9 and fig. 1-4 to know the relationship between the concentration of the lubricant component and the friction coefficient of the solutions under different conditions and the lubrication effect thereof.

The results of the test conducted under the conditions of example 6, in comparison with table 3, show that, in the case where the antimicrobial component "chlorine dioxide" is 1ppm and the lubricating component "propylene glycol" is present at a concentration of 0.4 to 30mg/ml, the coefficient of friction of the solution is less than that of the control group, i.e., 0.0184, and therefore, the results under the conditions of example 6 show that, in the case where the lubricating component is a polyhydric alcohol and/or a salt thereof, the polyhydric alcohol "propylene glycol" is present at a concentration of 0.4 to 30mg/ml, and forms a solution having antimicrobial activity and lubricating effect with chlorine dioxide. As shown in fig. 1, as the concentration of propylene glycol increased from 0.4 mg/ml to 20 mg/ml, the coefficient of friction of the solution reached a minimum of 0.0019. As the concentration of propylene glycol increases, the coefficient of friction of the solution increases in turn. In example 6, the solution had good lubricity when the concentration of the lubricious component in the solution was between 0.4 mg/ml and 30mg/ml, and the solution had better lubricity when the concentration of the lubricious component was between 10 mg/ml and 30 mg/ml.

The results of the test conducted under the conditions of example 7, in comparison with table 3, show that, in the case where the antimicrobial component "chlorine dioxide" is 1ppm and the lubricating component "glycerin" is present in a concentration of 0.4 to 30mg/ml, the coefficient of friction of the solution is lower than that of the control group, i.e., 0.0184, and therefore, the results under the conditions of example 7 show that, in the case where the lubricating component is a polyhydric alcohol and/or a salt thereof, the polyhydric alcohol "glycerin" is present in a concentration of 0.4 to 30mg/ml, and forms a solution having antimicrobial activity and lubricating effect with chlorine dioxide. The results in FIG. 2 show that as the concentration of glycerol is increased from 0.4 mg/ml to 25 mg/ml, the coefficient of friction of the solution reaches a minimum of 0.0037. As the concentration of glycerol increases, the coefficient of friction of the solution increases in turn. In example 7, the solution had good lubricity when the concentration of the lubricious component in the solution was between 0.4 mg/ml and 30mg/ml, and the solution had better lubricity when the concentration of the lubricious component was between 10 mg/ml and 30 mg/ml.

The results of the test conducted under the conditions of example 8 in comparison with Table 3 show that, in the case where the antimicrobial component "chlorine dioxide" is 1ppm, the coefficient of friction of the lubricating component "hyaluronic acid" at a concentration of 0.01 to 5 mg/ml is smaller than that of the control group of 0.0184, and therefore, the results under the conditions of example 8 show that, when the lubricating component in the solution is glycosaminoglycan and/or a salt thereof, the glycosaminoglycan "hyaluronic acid" at a concentration of 0.01 to 5 mg/ml can form a solution having antimicrobial ability and lubricating effect with chlorine dioxide. As shown in FIG. 3, as the concentration of hyaluronic acid was increased from 0.01 mg/ml to 1 mg/ml, the friction coefficient of the solution reached a minimum value of 0.0033. When the concentration of hyaluronic acid increases upwards, the friction coefficient of the solution increases upwards in turn. In example 8, the solution had good lubricity when the concentration of the lubricious component in the solution was between 0.01 mg/ml and the solution had better lubricity when the concentration of the lubricious component was between 0.05 mg/ml and 5 mg/ml.

The results of the test conducted under the conditions of example 9 in comparison with table 3 show that, in the case where the antimicrobial component "chlorine dioxide" is 1ppm, the coefficient of friction of the lubricating component "hydroxypropylmethylcellulose" at a concentration of 0.24 to 10 mg/ml is smaller than that of the control group of 0.0184, and therefore, the results under the conditions of example 9 show that, in the case where the lubricating component is a cellulose mixed ether and/or a salt thereof, the cellulose mixed ether "hydroxypropylmethylcellulose" at a concentration of 0.24 to 10 mg/ml forms a solution having antimicrobial activity and lubricating effect with chlorine dioxide. As shown in fig. 4, as the concentration of hydroxypropylmethylcellulose was increased from 0.24 mg/ml to 5 mg/ml, the friction coefficient of the solution reached a minimum value of 0.0020. As the concentration of hydroxypropyl methylcellulose increases upward, the coefficient of friction of the solution increases in turn. In example 9, the solution had good lubricity when the concentration of the lubricious component in the solution was between 0.24 mg/ml and 10 mg/ml, and the solution had better lubricity when the concentration of the lubricious component was between 1.2 mg/ml and 10 mg/ml.

From the results of examples 6-9, it can be seen that the solutions of the present invention have both an antimicrobial component and a lubricating component, wherein the lubricating component is not limited to polyols and/or salts thereof, glycosaminoglycans and/or salts thereof, or cellulose mixed ethers and/or salts thereof, and that the solutions of the present invention are not limited to uses thereof, such as lubricating solutions for contact lens care solutions or sterile equipment. In the embodiment of the present invention, since the molecular sizes of the different types of the lubricant components are different, the lubricant components have different suitable additive concentrations. For example, a relatively small molecular weight lubricating component such as a polyol and/or salts thereof may have a relatively high concentration of additive, and a relatively large molecular weight lubricating component such as a glycosaminoglycan and/or salts thereof or such as cellulose mixed ethers and/or salts thereof may have a relatively low concentration of additive.

In view of the above, the technical effects of the solution with high antimicrobial activity and lubricating effect according to the embodiments of the present invention are described below.

In the prior art, the disinfecting component and the lubricating component of the contact lens solution are difficult to combine, because the antimicrobial component and the lubricating component are difficult to be compatible, and the antimicrobial component and the lubricating component even mutually offset the efficacy of each other, so that the antimicrobial and lubricating effects are discounted. In contrast to the solutions of the present invention which have high antimicrobial and lubricating properties, the solutions of the present invention can comprise both antimicrobial and lubricating components, and only need low concentrations of the antimicrobial components to be effective, and are sufficiently competitive in various industries (e.g., contact lenses, mechanical devices).

The present invention is capable of other embodiments, and various changes and modifications may be made by one skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.

Claims

1. A solution having high antimicrobial capacity and lubricating effect, said solution comprising:

an antimicrobial component; and

a lubricating component;

wherein the concentration of the antimicrobial component is from 1 to 3000ppm and the antimicrobial capacity of the solution is: at a concentration of at least 1ppm of the antimicrobial component, the solution is exposed to a target for at least 300 seconds and kills greater than 90% of the microorganisms; or the antimicrobial component is at a concentration of at least 10ppm, the solution contacts a target for at least 10 seconds and kills greater than 90% of the microorganisms.

2. The solution of claim 1, wherein the microorganism is a bacterium, fungus, or virus.

3. The solution of claim 1, wherein the concentration of the lubricious component is from 0.01 to 30 mg/ml.

4. A solution having high antimicrobial capacity and lubricating effect consisting of chlorine dioxide and a lubricating ingredient, wherein the concentration of said chlorine dioxide is 1 to 3000ppm and the concentration of said lubricating ingredient is 0.01 to 30 mg/ml.

5. The solution of claim 4, wherein the lubricious component comprises: at least one of a polyol, a salt of a polyol, a glycosaminoglycan, a salt of a glycosaminoglycan, a cellulose mixed ether, and a salt of a cellulose mixed ether.

6. The solution of claim 5, wherein where the lubricious component is a polyol and/or a salt thereof, the polyol and/or a salt thereof is present at a concentration of 0.4 to 30 mg/ml; in the case where the lubricating ingredient is a glycosaminoglycan and/or a salt thereof, the concentration of the glycosaminoglycan and the salt thereof is 0.01 to 5 mg/ml; and when the lubricating component is cellulose mixed ether and/or salts thereof, the concentration of the cellulose mixed ether and the salts thereof is 0.24-10 mg/ml.

7. The solution of claim 5, wherein where the lubricious component is a polyol and/or a salt thereof, the polyol and/or a salt thereof is present in a concentration of 10 to 30 mg/ml; in the case that the lubricating component is glycosaminoglycan and/or its salt, the concentration of the glycosaminoglycan and/or its salt is 0.05-5 mg/ml; and in the case that the lubricating component is cellulose mixed ether and/or salts thereof, the concentration of the cellulose mixed ether and/or salts thereof is 1.2-10 mg/ml.

8. The solution of any one of claims 5 to 7, wherein the polyol is glycerol, propylene glycol, octanediol, ethylhexylglycerol, hexylene glycol, xylitol, polyethylene glycol, polypropylene glycol, or pentane glycol.

9. The solution of any one of claims 5 to 7, wherein the glycosaminoglycan is hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate, or heparin.

10. The solution of any one of claims 5 to 7, wherein the cellulose mixed ether is methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, carboxymethyl cellulose, or hydroxyethyl cellulose.