A medical water-soluble lubricant and its preparation method

Abstract

The present invention relates to A61L31, and more specifically, to a medical water-soluble lubricant and a preparation method thereof. The raw materials of the medical water-soluble lubricant include 6-16 parts by weight of high-polymerization degree polyethylene glycol, 4-10 parts by weight of low-polymerization degree polyethylene glycol, 0.4-1.0 parts by weight of a glue-adjusting base, 0.2-0.5 parts by weight of a polysaccharide active substance, 1.5-4 parts by weight of a lubricating moisturizer, 0.01-0.1 parts by weight of an antibacterial agent, and 72-85 parts by weight of water. The medical lubricant system provided by the present invention, which is mainly made of high-polymerization degree polyethylene glycol and supplemented by a specific cross-linked resin selected as a glue-adjusting base, not only has high cohesion and effectively enhances the protection of the tissue mucosa in frictional contact, but also overcomes the problem that, in a carbomer system, carbomer gel is easily moldy when exposed to air and affects ductility and viscosity, thereby improving the stability of the medical lubricant and maintaining substantially no change in cohesion when the temperature is too high or too low, or in sunlight.

Description

Technical Field

[0001] The present invention relates to the technical field of medical lubricants, and more particularly to a medical water-soluble lubricant and a preparation method thereof. Background Art

[0002] Medical water-soluble lubricants are currently commonly used in clinical examinations. They can be categorized into three main product lines: carbomer, xanthan gum, and (hydroxymethyl) cellulose. Carbomer water-soluble lubricants, with their superior ductility and light transmittance, have become a new generation mainstream product for clinical examinations.

[0003] Patent No. CN103203042A provides a water-soluble medical lubricant that adds polyethylene glycol-300 and polyethylene glycol-1450, which has a deodorizing effect, to carbomer, ensuring product safety. Patent No. CN111298201A provides a medical lubricant and its preparation method. By mixing different types of carbomer with polyethylene glycol-400, PEG-1500, and PEG-4000 in a system containing hyaluronic acid, the lubricant has good water retention during storage.

[0004] However, the high ductility of currently available carbomer-based water-soluble lubricants prevents them from being retained in a specific area for a long time or in a large amount, resulting in low adhesion between the lubricant and the surface of medical devices. This can weaken the effective protection of the mucous membranes in contact with friction. Summary of the Invention

[0005] In order to solve the above problems, the first aspect of the present invention provides a medical water-soluble lubricant, the raw materials of which include 6-16 parts by weight of high-polymerization degree polyethylene glycol, 4-10 parts by weight of low-polymerization degree polyethylene glycol, 0.4-1.0 parts by weight of glue-adjusting base, 0.2-0.5 parts by weight of polysaccharide active substance, 1.5-4 parts by weight of lubricant, 0.01-0.1 parts by weight of antibacterial agent and 72-85 parts by weight of water.

[0006] As a preferred technical solution of the present invention, the relative molecular mass of the high-polymerization polyethylene glycol is 5000-8000, and the hydroxyl value is 17-20 mgKOH / g.

[0007] As a preferred technical solution of the present invention, the relative molecular mass of the low-polymerization polyethylene glycol is 400-800, and the hydroxyl value is 160-220 mgKOH / g.

[0008] Preferably, the relative molecular mass of the high-polymerization polyethylene glycol is 9-10.8 times the relative molecular mass of the low-polymerization polyethylene glycol.

[0009] The adhesive base is selected from at least one of hydroxymethyl cellulose, xanthan gum, and carbomer. However, the applicant has found in research that xanthan gum, hydroxymethyl cellulose, and the like have poor ductility when used as medical lubricants. Therefore, the adhesive base described in this application is carbomer. However, when carbomer is selected, the adhesion between the medical lubricant and the surface of the medical device is low, resulting in the risk of weakened tissue mucosal protection. Therefore, the applicant has proposed a medical lubricant system using high-polymerization polyethylene glycol as the main raw material and a specific cross-linked resin as the adhesive base as a supplement. This not only improves the above-mentioned problems but also improves the stability of the medical lubricant. Its viscosity does not change substantially at high or low temperatures. The applicant infers that the high-polymerization polyethylene glycol has a higher relative molecular weight, resulting in a longer linear structure and a certain degree of entanglement with the low-polymerization polyethylene glycol, giving the system a specific three-dimensional curved pore structure. At the same time, the specific hydroxyl value environment of the system affects the swelling of the cross-linked acrylic resin in water, making the cross-linked network of the above structure more dense, thereby improving stability. The above effect is particularly evident when the relative molecular mass of high-polymerization polyethylene glycol is 9-10.8 times that of low-polymerization polyethylene glycol, and the release effect of the adhesive matrix in the stomach is slow, making it particularly suitable for clinical use in gastroscopy. As a preferred technical solution of the present invention, the adhesive matrix is ​​a cross-linked acrylic resin.

[0010] Preferably, the cross-linked acrylic resin is Carbomer 974P.

[0011] As a preferred technical solution of the present invention, the polysaccharide active substance is a mixed polysaccharide, and the mixed polysaccharide includes β-1,3-glucan and β-1,6-glucan.

[0012] Preferably, the proportion of the polysaccharide active substance in the raw materials of the medical water-soluble lubricant is 0.2-0.5 wt%.

[0013] More preferably, the proportion of the polysaccharide active substance in the raw materials of the medical water-soluble lubricant is 0.2-0.41 wt%.

[0014] The safety of medical lubricants can be improved by adding polysaccharide active substances. However, these active substances can affect the viscosity of the medical lubricants of this application, thereby affecting the lubricant's coefficient of friction. The applicants have discovered that by adding 0.2-0.5 wt% of a mixed polysaccharide of β-1,3-glucan and β-1,6-glucan to the system, they not only achieve sufficient and effective lubrication but also resolve the conflicting issues between the product's ductility and adhesion. This is likely due to the intermolecular hydrogen bonds forming a triple helical structure on the glucose rings of the complex polysaccharide chains in the mixed polysaccharide of β-1,3-glucan and β-1,6-glucan. This structure can interact with the polyethylene glycol (PEG) acting as the active agent, further affecting the swelling of the cross-linked acrylic resin.

[0015] Preferably, the lubricating moisturizer is glycerin.

[0016] As a preferred technical solution of the present invention, the antibacterial agent is at least two selected from methylparaben, ethylparaben, propylparaben and butylparaben.

[0017] As a preferred technical solution of the present invention, the antibacterial agents are methylparaben and propylparaben, and the weight ratio of methylparaben to propylparaben is 0.06:0.04.

[0018] As a preferred technical solution of the present invention, the weight ratio of the high-polymerization degree polyethylene glycol, low-polymerization degree polyethylene glycol, glue-adjusting matrix and polysaccharide active substance is (6-16): (4-10): (0.4-1.0): (0.2-0.5).

[0019] Furthermore, when the weight ratio of the high-polymerization degree polyethylene glycol, the low-polymerization degree polyethylene glycol, the adhesive base and the polysaccharide active substance is (6-16): (4-10): (0.4-1.0): (0.2-0.5), the viscosity of the prepared medical lubricant remains basically unchanged after high-low temperature cycling; in particular, when the relative molecular mass of the polyethylene glycol is 6000, the relative molecular mass of the low-polymerization degree polyethylene glycol is 600, the adhesive base is carbomer 974, and the polysaccharides are β-1,3-glucan and β-1,6-glucan, the prepared medical lubricant is placed at 40°C and 75% humidity for half a year, and the viscosity change does not exceed 30%, and the viscosity remains basically unchanged after high-low temperature cycling, which has good commercial value.

[0020] By combining the raw materials of the lubricating product of the present invention with a certain amount of the adhesive matrix, the influence of subsequent irradiation sterilization on the viscosity of the product is reduced, so that the lubricant product has excellent viscosity stability.

[0021] The second aspect of the present invention provides a method for preparing a medical water-soluble lubricant, which is as follows: S1: heating and melting once; S2: heating and melting twice; S3: cooling and mixing; S4: adjusting the pH to form a gel.

[0022] As a preferred technical solution of the present invention, step S4 adjusts the pH to 6.5-7.5.

[0023] Preferably, the preparation method is specifically as follows:

[0024] S1: heating and melting once; mixing high-polymerization degree polyethylene glycol and low-polymerization degree polyethylene glycol, heating at 60-90°C for 18-22 minutes to obtain a first mixture;

[0025] S2: Secondary heating and melting: the first mixture and the antibacterial agent are mixed and heated at 60-90°C for 18-22 minutes to obtain a second mixture;

[0026] S3: Cooling and mixing: The second mixture is cooled to room temperature, lubricant and moisturizer and water are added, stirred for 30-50 minutes, and polysaccharide active substance and adhesive base are added to obtain a third mixture; the above operation is conducive to the dispersion of the adhesive base and prevents agglomeration;

[0027] S4: pH adjustment: Add 18-20 wt% sodium hydroxide aqueous solution to the third mixture to adjust the pH to 6.5-7.5. A pH of 6.5-7.5 allows the chains of the adhesive matrix to stretch, facilitates gel formation, and maintains stable viscosity.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The medical lubricant system provided by the present invention, which uses high-polymerization polyethylene glycol as the main raw material and a specific cross-linked resin as a glue-adjusting matrix, not only has high adhesion and effectively enhances the protection of tissue mucosa in frictional contact, but also overcomes the problem of carbomer systems, in which carbomer gel is easily moldy when exposed to air, which affects its ductility and viscosity. It also improves the stability of the medical lubricant, and its viscosity remains essentially unchanged at high or low temperatures. This effect is particularly evident when the relative molecular weight of the high-polymerization polyethylene glycol is 9-10.8 times that of the low-polymerization polyethylene glycol. The glue-adjusting matrix has a slow release effect in the stomach, making it particularly suitable for clinical use in gastroscopy. The addition of 0.2-0.5wt% of a mixed polysaccharide of β-1,3-glucan and β-1,6-glucan to the system further improves lubricity without significantly affecting the viscosity of the lubricant. When the weight ratio of high-polymerization degree polyethylene glycol, low-polymerization degree polyethylene glycol, glue-adjusting matrix and polysaccharide active substance is controlled to (6-16): (4-10): (0.4-1.0): (0.2-0.5), the medical lubricant has good cleanliness, ensuring adhesion and lubricity while leaving basically no residue on the medical device after use.

[0030] The colorless, highly translucent medical lubricant provided by the present invention has suitable viscosity and lubricity, and is highly comfortable for the product and tissue; it also meets biological evaluation requirements and has no cytotoxicity. DETAILED DESCRIPTION

[0031] Example

[0032] The raw materials for preparing the compositions in the examples are all commercially available. Among them, polyethylene glycol 600 was purchased from Dow Chemical, USA, and is pharmaceutical grade, with a relative molecular weight of 540-660 and a hydroxyl value of 170-208 mgKOH / g; polyethylene glycol 6000 was purchased from Xi'an Tianzheng Pharmaceutical Excipients Co., Ltd., with a relative molecular weight of 5500-7000 and a hydroxyl value of 17.5-20 mgKOH / g; polyethylene glycol 400 was purchased from Xi'an Jinxiang Pharmaceutical Excipients Co., Ltd. and is pharmaceutical grade; polyethylene glycol 1500 was purchased from Xi'an Tianzheng Pharmaceutical Excipients Co., Ltd. and is pharmaceutical grade; carbomer 974P was purchased from Lubrizol, item number 974Pnf; mixed polysaccharides were purchased from Nanjing Taixin Biotechnology Co., Ltd., product name yeast β-glucan, and the mixed polysaccharides include β-1,3-glucan and β-1,6-glucan.

[0033] Example 1

[0034] This example provides a medical water-soluble lubricant, the raw materials of which include 10 parts by weight of high-polymerization degree polyethylene glycol, 6 parts by weight of low-polymerization degree polyethylene glycol, 0.6 parts by weight of glue-adjusting base, 0.2 parts by weight of polysaccharide active substance, 2 parts by weight of lubricating moisturizer, 0.1 parts by weight of antibacterial agent and 82.2 parts by weight of water.

[0035] The high-polymerization polyethylene glycol is polyethylene glycol 6000, the low-polymerization polyethylene glycol is polyethylene glycol 600, the adhesive base is a cross-linked acrylic resin, and the cross-linked acrylic resin is carbomer 974P. The polysaccharide active ingredient is a mixed polysaccharide. The lubricant and moisturizer is glycerin.

[0036] The antibacterial agents are methylparaben and propylparaben, and the weight ratio of methylparaben to propylparaben is 0.06:0.04.

[0037] This example also provides a preparation method of a medical water-soluble lubricant, the preparation method is specifically as follows:

[0038] S1: heating and melting once; mixing high-polymerization degree polyethylene glycol and low-polymerization degree polyethylene glycol, heating at 70°C for 20 minutes to obtain a first mixture;

[0039] S2: Secondary heating and melting: the first mixture and the antibacterial agent are mixed and heated at 70°C for 20 minutes to obtain a second mixture;

[0040] S3: Cooling and mixing: The second mixture is cooled to 25°C, a lubricant and moisturizer and water are added, stirred for 40 minutes, and the polysaccharide active substance and the adhesive base are added to obtain a third mixture;

[0041] S4: Adjusting pH: adding a 20 wt % sodium hydroxide aqueous solution to the third mixture to adjust the pH to 6.8.

[0042] Example 2

[0043] This example provides a medical water-soluble lubricant. Unlike Example 1, this example provides a medical water-soluble lubricant. The raw materials of the medical water-soluble lubricant include 10 parts by weight of high-polymerization degree polyethylene glycol, 6 parts by weight of low-polymerization degree polyethylene glycol, 0.8 parts by weight of glue-adjusting base, 2 parts by weight of lubricating moisturizer, 0.1 parts by weight of antibacterial agent and 82.2 parts by weight of water.

[0044] This example also provides a preparation method of a medical water-soluble lubricant, which is the same as that of Example 1.

[0045] Example 3

[0046] This example provides a medical water-soluble lubricant. The difference from Example 2 is that the high-polymerization degree polyethylene glycol is polyethylene glycol 1500, and the low-polymerization degree polyethylene glycol is polyethylene glycol 400.

[0047] This example also provides a preparation method of a medical water-soluble lubricant, which is the same as that of Example 2.

[0048] Performance testing:

[0049] 1. Viscosity measurement: The dynamic viscosity of Examples 1-3 is shown in Table 1 below;

[0050] Table 1

[0051] sample Example 1 Example 2 Example 3 Viscosity (mPa·s) 34150 45350 39900

[0052] 2. Viscosity stability test: The medical water-soluble lubricant of Example 1 and the medical lubricant of Example 1 were placed at 40°C and 75% humidity for half a year, and then the viscosity was tested at 25°C (Condition 0). The viscosity was then tested again at 50°C for 72 hours (Condition 1) and at -18°C for 72 hours (Condition 2). The results are shown in Table 2.

[0053] Table 2

[0054] Example Condition 0 (mPa·s) Condition 1 (mPa·s) Condition 2 (mPa·s) Example 1 34150 32100 32000 After accelerated aging 27700 27000 24750

Claims

1. A medical water-soluble lubricant, characterized in that: The raw materials of the medical water-soluble lubricant include 6-16 parts by weight of high-polymerization degree polyethylene glycol, 4-10 parts by weight of low-polymerization degree polyethylene glycol, 0.4-1.0 parts by weight of glue-adjusting base, 0.2-0.5 parts by weight of polysaccharide active substance, 1.5-4 parts by weight of lubricating moisturizer, 0.01-0.1 parts by weight of antibacterial agent and 72-85 parts by weight of water; The relative molecular mass of the high-polymerization polyethylene glycol is 5000-8000, and the hydroxyl value is 17-20 mgKOH / g; the relative molecular mass of the low-polymerization polyethylene glycol is 400-800, and the hydroxyl value is 160-220 mgKOH / g; the relative molecular mass of the high-polymerization polyethylene glycol is 9-10.8 times the relative molecular mass of the low-polymerization polyethylene glycol; The glue adjustment matrix is ​​Carbomer 974P; The polysaccharide active substance includes β-1,3-glucan and β-1,6-glucan; the proportion of the polysaccharide active substance in the raw materials of the medical water-soluble lubricant is 0.2-0.41wt%.

2. The medical water-soluble lubricant according to claim 1, characterized in that: The antibacterial agent is selected from at least two of methylparaben, ethylparaben, propylparaben and butylparaben.

3. The medical water-soluble lubricant according to claim 2, characterized in that: The antibacterial agents are methylparaben and propylparaben, and the weight ratio of methylparaben to propylparaben is (0-0.06): (0-0.04).

4. The medical water-soluble lubricant according to any one of claims 1 to 3, characterized in that: The weight ratio of the high-polymerization degree polyethylene glycol, the low-polymerization degree polyethylene glycol, the glue-adjusting matrix and the polysaccharide active substance is (6-16): (4-10): (0.4-1.0): (0.2-0.5).

5. A method for preparing the medical water-soluble lubricant according to claim 1, characterized in that: The preparation method is as follows: S1: heating and melting once; mixing high-polymerization degree polyethylene glycol and low-polymerization degree polyethylene glycol, and heating at 60-90° C. for 18-22 minutes to obtain a first mixture; S2: Secondary heating and melting: the first mixture and the antibacterial agent are mixed and heated at 60-90°C for 18-22 minutes to obtain a second mixture; S3: Cooling and mixing: The second mixture is cooled to room temperature, a lubricant and moisturizer and water are added, stirred for 30-50 minutes, and the polysaccharide active substance and the adhesive base are added to obtain a third mixture; S4: Adjusting pH: adding an aqueous sodium hydroxide solution with a concentration of 18-20 wt % to the third mixture to adjust the pH to 6.5-7.5.