WO2020140365A1 - Moisturizing and lubricating composition containing xanthan gum and use thereof - Google Patents

Abstract

Provided is a moisturizing and lubricating composition containing xanthan gum, comprising the following components in mass percentages: 0.005-2.5％ of xanthan gum, 0.005-15％ of a buffering agent, 0.0005-10％ of a surfactant, 0.0005-5％ of a chelating agent, 0.00005-0.005％ of an antimicrobial agent, 0.005-5％ of an osmotic pressure regulator, and the balance of water for injection; and the composition can be used for treating contact lenses as a care solution for contact lenses.

Description

Moisturizing and lubricating composition containing xanthan gum and application thereof Technical field

The invention belongs to the field of medical equipment, and particularly relates to a moisturizing and lubricating composition containing xanthan gum and its application.

Background technique

With the popularity of contact lenses, various types of contact lens care solutions have also been launched one after another. Its basic function is to clean, disinfect, and deproteinize contact lenses. But the main aspects that affect the wearer's experience are moisturizing and lubricating. If the moisture retention is insufficient, the liquid between the cornea and the contact lens will be insufficiently filled, and the lack of lubricity will increase the friction between the lens and the eye surface. Therefore, after wearing the lens, users are prone to problems such as dry and uncomfortable eyes, corneal damage and inflammation. The commonly used moisturizing and lubricating factors are mainly hyaluronic acid (HA), sodium pyrrolidone carboxylate (PCA), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), glycerin, propylene glycol, sorbitol and so on.

Each moisturizing lubricant has certain advantages and disadvantages: PCA is a moisturizing factor that naturally exists in the skin. The moisturizing and hygroscopic properties are significantly better than glycerin, propylene glycol, and sorbitol. However, the moisturizing effect of PCA must be in a high humidity environment. When the air humidity is low, it makes the skin more dry. PVP and PVA are high-molecular compounds. Although they are both water-soluble substances, the degree of stretch of their molecular chains in aqueous solution is not ideal, and PVA has a stimulating effect on the eyes. HA is an acidic mucopolysaccharide, which is also a component of the human body. It is the best moisturizing substance found in nature and is called the ideal natural moisturizing factor. Although HA has good water absorption and moisturizing properties, its production cost is high, and there are many factors affecting the moisturizing and lubricating properties, such as pH enzymes, reducing substances, ultraviolet rays, etc., and its stability is very poor. The difference in technology has a significant impact on the effect.

Xanthan gum is a kind of microbial extracellular polysaccharide produced by fermentation using sugar as the main raw material. In 1969, xanthan gum was first approved by the US FDA for use in foods and medicines. It is now used as a pharmaceutical excipient in the 2010 version of China Pharmacopoeia has good biological safety. The literature has confirmed that xanthan gum can be used to treat eye diseases and increase the bioavailability of ophthalmic drugs.

Studies in the prior art have shown that xanthan gum solutions have higher viscosity at low concentrations and are used as thickeners, suspending agents, emulsifiers, and stabilizers in liquid and semi-solid formulations. The high viscosity of xanthan gum makes it easier for external preparations to be coated, and not easy to fall off from the skin, which helps to improve the bioavailability of the drug and increase the comfort of the drug. In ophthalmic preparations, xanthan gum is used as an eye drop aid to prolong the contact time between the drug and the site of application. Due to the nature of its pseudoplastic fluid, the shear force generated during blinking can rapidly reduce its viscosity without causing discomfort to the eyes. Eye drops prepared by mixing xanthan gum, chondroitin sulfate, and sodium hyaluronate can protect corneal epithelial cells and accelerate cell regeneration. The ophthalmic gel prepared with xanthan gum as the gel matrix is uniform, stable, and has good gel strength. It has a good bioadhesive effect on the corneal surface, can significantly prolong the drug residence time and improve the efficacy, and delay the drug release. The research results show that xanthan gum is more stable than sodium hyaluronate, is not easily degraded by enzymes and free radicals in the body, and has a longer residence time.

At present, when people wear contact lenses, the eyes are dry and uncomfortable due to the limited lubricity. Usually, eye drops are added for secondary lubrication and moisturization. However, can xanthan gum be used in contact lens care solutions? How much can be added to have a better moisturizing and lubricating effect than the existing contact lens care solution, and related solutions have not been provided in the prior art.

Chinese invention patent application with publication number 106860903A discloses a contact lens care solution, including sodium pyrrolidone carboxylate, quaternary ammonium salt chitosan, vitamin B ₆ , plant extract, etc., wherein the moisturizer is quaternary ammonium salt chitosan . Quaternary ammonium salt chitosan has good biocompatibility, no immunogenicity and inflammation, no toxicity to eye tissue, no harmful degradation products, but it does not have a lubricating effect, and its moisturizing properties are not as good as hyaluronic acid.

The Chinese invention patent application with publication number CN1390606A discloses a composition for treating contact lenses and its application. The composition contains sodium hyaluronate 0.001-0.5%, nonionic surfactant 0.001-10%, chelate Mixture 0.01-10%, buffer 0.05-2.5%, tonicity agent, bactericide, water, in which the moisturizing agent is sodium hyaluronate. Although sodium hyaluronate has good water absorption and moisturizing properties, its production cost is high, and there are many factors affecting the moisturizing and lubricating properties, such as pH enzymes, reducing substances, ultraviolet rays, etc., the stability is very poor, and also because of the source of raw materials And the difference in manufacturing technology has a significant impact on the effect.

Summary of the invention

In order to solve the above-mentioned problems, on the one hand, the present invention provides a moisturizing and lubricating composition containing xanthan gum. According to the mass percentage, the composition includes: xanthan gum 0.005%-2.5%, buffer 0.005%-15 %, surfactant 0.0005%-10%, chelating agent 0.0005%-5%, bacteriostatic agent 0.00005%-0.005%, osmotic pressure regulator 0.005%-5%, and the rest is water for injection.

Further, in terms of mass percentage, the composition includes: xanthan gum 0.01%-2%, buffer 0.01%-10%, surfactant 0.001%-5%, chelating agent 0.001%-3%, bacteriostatic Agent 0.00005%-0.002%, osmotic pressure regulator 0.01%-4%.

Further, the mass-volume ratio of xanthan gum is 0.1%-1.0%.

Preferably, the mass-volume ratio of xanthan gum is selected from 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.2%, 1.5%, 2.0% .

Further, the molecular weight of the xanthan gum is 10-20 million, preferably 1-5 million, more preferably 1 million, 2 million, 3 million, 4 million, 5 million.

Further, the pH range of the composition is 6-8, preferably 7-7.5, more preferably 7.4.

Further, the osmotic pressure of the composition is 220-350 mOsm/(Kg·H2O), preferably 290 mOsm/(Kg·H2O).

Furthermore, the osmotic pressure of the composition is adjusted by an osmotic pressure regulator, wherein the osmotic pressure regulator is one selected from sodium chloride, glucose, boric acid, and borax, preferably sodium chloride.

Further, the buffering agent is selected from a mixture of any one or more of phosphate, carbonate, borate and citrate, preferably borate buffering agent. The above buffering agent not only has a buffering effect, but also can assist sterilization, and has low toxicity.

The bacteriostatic agent is selected from the group consisting of sorbic acid, polyhexamethylene biguanide hydrochloride (PHMB), polyaminopropyl biguanide (PAPB), and iodine, preferably polyhexamethylene Biguanide hydrochloride. The above bacteriostatic agent has high safety and little irritation to eyes.

The chelating agent is selected from ethylenediaminetetraacetic acid (EDTA) and its sodium salt, glycine, citric acid, succinic acid, tartaric acid, boric acid, phosphate, or any combination thereof, preferably ethylenediaminetetraacetic acid diacetate Sodium (EDTA-2Na). The above chelating agent is used to bind metal ions to prevent the metal ions from reacting with the protein accumulated on the lens and assist in sterilization.

The surfactant is a mixture of one or more selected from poloxamers, polyethylene glycol, glycerides, glucose esters, polysorbates, alkyl glycosides, and polysiloxanes, preferably poloxamers , More preferably Poloxamer 407. The above surfactants not only have a cleaning effect on the deposits on contact lenses, but also can remove proteins, lipids and debris on the surface of the lens. They also have good biocompatibility and are non-irritating to the eyes.

On the other hand, the present invention also provides the use of the above composition in the treatment of contact lenses. Preferably, the composition is used for cleaning, lubricating and/or storing contact lenses.

On the other hand, the present invention also provides the application of xanthan gum in the preparation of contact lens care solution, wherein the contact lens care solution includes: xanthan gum 0.005%-2.5%, buffer 0.005%-15%, surfactant 0.0005 %-10%, chelating agent 0.0005%-5%, bacteriostatic agent 0.00005%-0.005%, osmotic pressure regulator 0.005%-5%, the rest is water for injection; the molecular weight of the xanthan gum is 10-20 million.

On the other hand, the present invention also provides the application of the above composition in the preparation of contact lens care solution.

In another aspect, the present invention also provides a contact lens care solution comprising the above composition having moisturizing and lubricating properties.

Through this application can bring the following beneficial effects:

1. The composition provided by the present invention, using xanthan gum with a certain mass fraction and molecular weight as a moisturizing lubricant, shows excellent lubricating and moisturizing properties, and can be used as a contact lens care solution to clean, lubricate and store contact lenses According to the test data, the lubricity and moisturizing properties of xanthan gum in contact lens care solution are better than hyaluronic acid, which can effectively reduce the wear between contact lens and cornea and improve the wearing comfort.

2. The contact lens treated with the composition provided by the present invention can avoid the decrease of lubricity caused by tearing; keep the liquid filling between the corneal cells and the contact lens for a long time to moisturize the eye for a long time; very stable to acid and alkali , Its properties are not affected at a pH between 5 and 10, including lubricity; the humidity retention and comfort when worn are improved, and xanthan gum also has a protective effect on corneal epithelial cells. The corneal damage caused has a repairing effect.

3. The contact lens care solution provided by the present invention, composed of the composition provided by the present invention, has higher biological safety. Compared with the hyaluronic acid as the lubricant care solution, it can provide better lubrication and moisturizing effect, even It can also be used to moisturize the eye when not wearing glasses.

detailed description

In order to more clearly explain the overall concept of the present application, the following describes in detail by way of examples. In the following description, a large number of specific details are given in order to provide a more thorough understanding of the present invention. However, it is obvious to those skilled in the art that the present invention can be implemented without one or more of these details. In other examples, in order to avoid confusion with the present invention, some technical features known in the art are not described.

Unless otherwise stated, in the following examples, xanthan gum was obtained by fermentation of Xanthomonas, the remaining raw material components were purchased commercially, and the four-ball friction and wear test machine used in the lubrication effect experiment was purchased from the Jinan test machine Factory, model is MRS-1J.

Example 1:

A composition with moisturizing and lubricating properties, comprising the following components and proportions: xanthan gum 0.1% (Mw = 1 million), PHMB 0.0001%, poloxamer 407 0.05%, EDTA-2Na 0.02%, boric acid Salt buffer (pH 7.4) was added to 100 mL, and NaCl was added to adjust the osmotic pressure of the care solution to 290 mOsm/(Kg·H ₂ O). Among them, the water used is water for injection.

Example 2:

A composition with moisturizing and lubricating properties, comprising the following components and proportions: xanthan gum 0.5% (Mw = 1 million), PHMB 0.0001%, poloxamer 407 0.05%, EDTA-2Na 0.02%, boric acid Salt buffer (pH 7.4) was added to 100 mL, and NaCl was added to adjust the osmotic pressure of the care solution to 290 mOsm/(Kg·H ₂ O). Among them, the water used is water for injection.

Example 3:

A composition with moisturizing and lubricating properties, comprising the following components and proportions: xanthan gum 1.0% (Mw = 1 million), PHMB 0.0001%, poloxamer 407 0.05%, EDTA-2Na 0.02%, boric acid Salt buffer (pH 7.4) was added to 100 mL, and NaCl was added to adjust the osmotic pressure of the care solution to 290 mOsm/(Kg·H ₂ O). Among them, the water used is water for injection.

Example 4:

A composition with moisturizing and lubricating properties, comprising the following components and proportions: xanthan gum 0.1% (Mw = 3 million), PHMB 0.0001%, poloxamer 407 0.05%, EDTA-2Na 0.02%, boric acid Salt buffer (pH 7.4) was added to 100 mL, and NaCl was added to adjust the osmotic pressure of the care solution to 290 mOsm/(Kg·H ₂ O). Among them, the water used is water for injection.

Example 5:

A composition with moisturizing and lubricating properties, comprising the following components and proportions: xanthan gum 0.5% (Mw = 3 million), PHMB 0.0001%, poloxamer 407 0.05%, EDTA-2Na 0.02%, boric acid Salt buffer (pH 7.4) was added to 100 mL, and NaCl was added to adjust the osmotic pressure of the care solution to 290 mOsm/(Kg·H ₂ O). Among them, the water used is water for injection.

Example 6:

A composition with moisturizing and lubricating properties, comprising the following components and proportions: xanthan gum 1.0% (Mw = 3 million), PHMB 0.0001%, poloxamer 407 0.05%, EDTA-2Na 0.02%, boric acid Salt buffer (pH 7.4) was added to 100 mL, and NaCl was added to adjust the osmotic pressure of the care solution to 290 mOsm/(Kg·H ₂ O). Among them, the water used is water for injection.

Example 7:

A composition with moisturizing and lubricating properties, comprising the following components and proportions: xanthan gum 0.1% (Mw = 5 million), PHMB 0.0001%, poloxamer 407 0.05%, EDTA-2Na 0.02%, boric acid Salt buffer (pH 7.4) was added to 100 mL, and NaCl was added to adjust the osmotic pressure of the care solution to 290 mOsm/(Kg·H ₂ O). Among them, the water used is water for injection.

Example 8:

A composition with moisturizing and lubricating properties, comprising the following components and proportions: xanthan gum 0.5% (Mw = 5 million), PHMB 0.0001%, poloxamer 407 0.05%, EDTA-2Na 0.02%, boric acid Salt buffer (pH 7.4) was added to 100 mL, and NaCl was added to adjust the osmotic pressure of the care solution to 290 mOsm/(Kg·H ₂ O). Among them, the water used is water for injection.

Example 9:

A composition with moisturizing and lubricating properties, comprising the following components and proportions: xanthan gum 1.0% (Mw = 5 million), PHMB 0.0001%, poloxamer 407 0.05%, EDTA-2Na 0.02%, boric acid Salt buffer (pH 7.4) was added to 100 mL, and NaCl was added to adjust the osmotic pressure of the care solution to 290 mOsm/(Kg·H ₂ O). Among them, the water used is water for injection.

Comparative Example 1:

A contact lens care solution, the formulation of which is a composition of the following components and proportion: hyaluronic acid (Mw = 1 million) 1.0%, PHMB 0.0001%, poloxamer 407 0.05%, EDTA-2Na0.02% , Borate buffer (pH 7.4) was added to 100mL, and NaCl was added to adjust the osmotic pressure of the care solution to 290mOsm/(Kg·H ₂ O). Among them, the water used is water for injection.

Among them, the compositions obtained in Examples 1-9 can be applied to contact lens care solutions. In a preferred embodiment, the method of using the composition provided by the present invention as a contact lens care solution is as follows:

Take out the contact lenses, add 3 to 5 drops of the care solution of the present invention to each lens and gently rub for 20 seconds, then rinse each side thoroughly for 3 to 5 times, then put it in the lens box, add the care solution of the present invention to soak for 30 minutes, remove it Can be worn.

Evaluation of lubricity and moisture retention:

Test 1: Determination of friction coefficient

For the determination method of friction coefficient μ, refer to the four-ball method in GB3142-90, and use a four-ball friction and wear tester to evaluate Examples 1-9, Comparative Examples 1-3, and 1.0% xanthan gum (Mw = 1 million), 1.0% hyaluronic acid The lubricating performance of acid (Mw = 1 million), the friction coefficient (load 30N) and wear scar diameter of each example were measured, and the diameter of the ceramic ball used was 12.7 mm. The experimental conditions were: speed 1450r/min, temperature 37℃, test time 30min. The results obtained are shown in Table 1.

Table 1 The friction coefficient of the compositions obtained in each example

Group	Friction coefficient μ	Wear scar diameterΦ(mm)
Example 1	0.197	1.62
Example 2	0.152	1.54
Example 3	0.126	1.36

Example 4	0.139	1.50
Example 5	0.113	1.32
Example 6	0.085	1.06
Example 7	0.107	1.23
Example 8	0.081	0.94
Example 9	0.062	0.83
Comparative Example 1	0.208	1.81
1.0% xanthan gum (Mw = 1 million)	0.161	1.56
1.0% hyaluronic acid (Mw = 1 million)	0.237	1.97

As can be seen from Table 1, compared with Comparative Example 1, Examples 1-9 showed a lower friction coefficient and a smaller wear scar diameter, indicating the lubricating of the contact lens care solution of xanthan gum in each molecular weight segment and concentration The performance is significantly better than hyaluronic acid. At the same time, the friction coefficients of Examples 6, 8 and 9 are smaller than those of other examples. Among them, the friction coefficient of Example 9 is the smallest, which is 0.062, indicating that the greater the concentration of xanthan gum, the greater the molecular weight , The lower the friction coefficient.

Comparing the friction coefficient of 1.0% xanthan gum (Mw = 1 million) and 1.0% hyaluronic acid (Mw = 1 million), the friction coefficient of xanthan gum is lower than hyaluronic acid at the same concentration and molecular weight , Indicating that the lubricating performance of the xanthan gum with individual components is superior to hyaluronic acid. However, from the friction coefficients of Examples 2-9, it can be seen that when the application of xanthan gum and other components in the application is prepared as a care solution, its lubricating performance is further improved, which shows that when combined with other ingredients of the application of the care solution When used, xanthan gum produced unexpected technical effects.

The above results show that the xanthan gum care solution contained in Examples 1-9 of the present invention has excellent lubricating properties and can increase the lubricating effect of contact lenses on the ocular surface.

Test 2: Use comfort and humidity retention test

Select 40 volunteers, try on the contact lenses soaked in Examples 1-9 and Comparative Example 1, and record the tester's feelings respectively to evaluate the wearing comfort and moisturization, feeling moisturizing and comfortable The evaluation standard is: when the wearing time exceeds 120 minutes, there is no dry eye, discomfort or foreign body sensation. Among them, the selected healthy adult volunteers had no eye diseases and had more than one contact lens wearing experience. See Table 2 for the evaluation results of the wearing comfort and moisture retention of the soaked contact lenses in each example.

Table 2 Evaluation of wearing comfort and moisturizing performance of each example

Group	Number of moisturizers (person)	Number of people who feel comfortable (person)
Example 1	29	28
Example 2	31	29
Example 3	32	34
Example 4	32	31
Example 5	35	32
Example 6	36	36
Example 7	34	35
Example 8	35	34
Example 9	35	36
Comparative Example 1	28	26

It can be seen from Table 2 that the number of people who feel moisturizing and comfortable in each example is more than that in Comparative Example 1. It is shown that when the composition provided by the present invention is used as a contact lens care solution, it shows better contact lens care solution than hyaluronic acid. Moisturizing properties can significantly improve the wearing comfort of contact lenses.

In summary, the composition provided by the present invention uses xanthan gum with a certain mass fraction and molecular weight as a moisturizing lubricant, shows excellent lubricating and moisturizing properties, and can be used as a contact lens care solution to clean and lubricate contact lenses 3. Storage. According to the test data, the lubricity and moisturizing properties of xanthan gum in contact lens care solution are better than hyaluronic acid, which can effectively reduce the wear between contact lens and cornea and improve the wearing comfort. When used as a contact lens care solution, it has high biological safety. Compared with hyaluronic acid as a lubricant care solution, it can provide better lubrication and moisturizing effect.

The above are only examples of the present application, and are not intended to limit the present application. For those skilled in the art, the present application may have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of this application shall be included in the scope of the claims of this application.

Claims (10)

1. A composition with moisturizing and lubricating properties, characterized in that, in terms of mass percentage, the composition includes: xanthan gum 0.005%-2.5%, buffering agent 0.005%-15%, surfactant 0.0005%-10% , Chelating agent 0.0005%-5%, bacteriostatic agent 0.00005%-0.005%, osmotic pressure regulator 0.005%-5%, the rest is water for injection.
2. The composition according to claim 1, characterized in that, in terms of mass percentage, the composition comprises: xanthan gum 0.01%-2%, buffer 0.01%-10%, surfactant 0.001%-5% , Chelating agent 0.001%-3%, antibacterial agent 0.00005%-0.002%, osmotic pressure regulator 0.01%-4%.
3. The composition according to claim 1, wherein the mass-volume ratio of the xanthan gum is 0.1%-1.0%.
4. The composition according to any one of claims 1 to 3, characterized in that the molecular weight of the xanthan gum is 10-20 million, preferably 1-5 million.
5. The composition according to any one of claims 1-3, characterized in that the pH range of the composition is 6-8, preferably pH 7.2-7.5, more preferably 7.4.
6. The composition according to any one of claims 1-3, characterized in that the osmotic pressure of the composition is 220-350 mOsm/(Kg·H ₂ O), preferably 290 mOsm/(Kg·H ₂ O).
7. The composition according to claim 6, characterized in that the osmotic pressure of the composition is adjusted by an osmotic pressure regulator selected from the group consisting of sodium chloride, glucose, boric acid, and borax, Sodium chloride is preferred.
8. The composition according to any one of claims 1 to 3, characterized in that the buffering agent is selected from the group consisting of any one or more of phosphate, carbonate, borate and citrate, preferably Borate buffer; the bacteriostatic agent is selected from the group consisting of sorbic acid, polyhexamethylene biguanide hydrochloride, polyaminopropyl biguanide, iodine, or a mixture of any one or more of them, preferably polyhexamethylene Biguanide hydrochloride; the chelating agent is selected from ethylenediaminetetraacetic acid and its sodium salt, glycine, citric acid, succinic acid, tartaric acid, boric acid, phosphate, any one or more of the mixture, preferably ethylenediamine Disodium tetraacetate; the surfactant is selected from a mixture of one or more of poloxamer, polyethylene glycol, glyceride, glucose ester, polysorbate, alkyl glycoside, polysiloxane, Poloxamer is preferred.
9. The application of xanthan gum in the preparation of contact lens care solution, characterized in that the contact lens care solution includes: xanthan gum 0.005%-2.5%, buffer 0.005%-15%, surfactant 0.0005%-10% 2. Chelating agent 0.0005%-5%, bacteriostatic agent 0.00005%-0.005%, osmotic pressure regulator 0.005%-5%, the rest is water for injection; the molecular weight of the xanthan gum is 10-20 million.
10. A contact lens care solution, characterized in that the contact lens care solution comprises the composition having moisturizing and lubricating properties according to claim 1.