Electrolyte-resistant dilute medical moisturizing repair hydrogel and preparation method thereof

Abstract

The application discloses a kind of electrolyte-resistant dilute type medical moisturizing repair hydrogel and preparation method thereof, belong to the technical field of hydrogel, the hydrogel includes the following mass ratio of component: acrylic acid sodium copolymer 0.4-0.6%, hydrophobic modified ethoxylated polyurethane 0.1-0.2%, sodium pyrrolidone carboxylate 1.2%, ceramide NP liposome 0.2-0.4%, ikd 0.2-0.4%, panthenol 0.4-0.6%, sodium hyaluronate 0.05-0.15%, carboxymethyl dextran 0.3-0.5%, phenoxyethanol 0.5-0.7%, octanol 0.2-0.4%, the rest is deionized water.The hydrogel can effectively solve the problem of viscosity of hydrogel caused by sodium pyrrolidone carboxylate, ceramide is difficult to dissolve and the problem such as poor transdermal property.

Description

Technical Field

[0001] This invention belongs to the field of hydrogel technology, specifically relating to an electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel and its preparation method. Background Technology

[0002] Medical-grade moisturizing and repairing hydrogels are widely used in post-cosmetic procedures, sensitive skin care, and chronic wound care, requiring excellent moisturizing, repairing, stability, and skin feel. Sodium pyrrolidone carboxylate (sodium PCA), as a highly effective moisturizer, can effectively regulate the moisture content of the stratum corneum. However, as a strong electrolyte, it easily ionizes in hydrogel systems to produce sodium ions, which neutralize the negative charge on the thickener molecular chains. This causes the thickener structure to collapse, the system viscosity to drop sharply, and severely affects product stability and user experience.

[0003] Meanwhile, ceramides, as a core active ingredient for skin barrier repair, are prone to aggregation and precipitation in hydrogels due to their strong hydrophobicity, resulting in low transdermal absorption efficiency and hindering their deep repair effects. Existing moisturizing and repairing hydrogels often use traditional thickeners such as carbomer and xanthan gum, which are sensitive to electrolytes and cannot be adapted to high-content sodium PCA systems. Although some patents employ liposome technology to encapsulate ceramides to improve their solubility and transdermal absorption, this does not solve the viscosity instability problem caused by electrolytes. Electrolyte-resistant hydrogels, on the other hand, often lack efficient ceramide delivery systems, resulting in limited repair effects.

[0004] Therefore, developing a medical moisturizing and repairing hydrogel that combines electrolyte stability, a thin and refreshing feel, efficient delivery of ceramides, and multi-functional repair is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0005] To address the aforementioned shortcomings in the prior art, this invention provides an electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel that effectively solves problems such as a sudden drop in viscosity caused by sodium PCA, poor solubility of ceramides, and poor transdermal permeability.

[0006] To achieve the above objectives, the technical solution adopted by the present invention to solve its technical problem is as follows:

[0007] An electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel comprises the following components in the indicated mass percentages: 0.4-0.6% sodium acrylate copolymer, 0.1-0.2% hydrophobically modified ethoxylated polyurethane, 1-1.5% sodium pyrrolidone carboxylate, 0.2-0.4% ceramide NP liposomes, 0.2-0.4% ectoine, 0.4-0.6% panthenol, 0.05-0.15% sodium hyaluronate, 0.3-0.5% carboxymethyl dextran, 0.5-0.7% phenoxyethanol, 0.2-0.4% octyl glycol, and the remainder being deionized water.

[0008] Further, the composition includes the following components by mass percentage: 0.5% sodium acrylate copolymer, 0.15% hydrophobically modified ethoxylated polyurethane, 1.2% sodium pyrrolidone carboxylate, 0.3% ceramide NP liposomes, 0.3% ectoine, 0.5% panthenol, 0.1% sodium hyaluronate, 0.4% carboxymethyl dextran, 0.6% phenoxyethanol, 0.3% octyl glycol, and the remainder being deionized water.

[0009] Furthermore, the sodium acrylate copolymer is a hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer.

[0010] Furthermore, the particle size of the ceramide liposomes is 50-200 nm.

[0011] Furthermore, sodium hyaluronate has a molecular weight of less than 100 kDa.

[0012] The preparation method of the above-mentioned electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel includes the following steps:

[0013] (1) Add sodium hyaluronate and carboxymethyl dextran to deionized water in sequence and stir until completely dissolved;

[0014] (2) Then add sodium pyrrolidone carboxylate and panthenol to it in sequence, and stir until completely dissolved;

[0015] (3) Continue to add sodium acrylate copolymer to it, stir until there is no dry powder and it is evenly dispersed, then add hydrophobically modified ethoxylated polyurethane, stir until it is fully swollen and crosslinked to form a stable thin gel substrate;

[0016] (4) Adjust the pH of the gel base to 6.0~6.5, and then add ceramide NP liposomes and ectoine under light-protected conditions. Mix at low speed and continue to adjust the pH to 6.0~6.5, homogenize, defoam, and obtain the finished product.

[0017] The beneficial effects of this invention are as follows:

[0018] In this invention, a hydrophilic skeleton of sodium acrylate copolymer provides basic support and water absorption, while hydrophobically modified ethoxylated polyurethane provides a hydrophobic network. The combination of sodium acrylate copolymer and hydrophobically modified ethoxylated polyurethane constructs an electrolyte-resistant double-network interpenetrating thickening system, forming an interpenetrating hydrophobic associative network structure, thereby enabling the hydrogel to achieve electrolyte resistance and thixotropy. This hydrophobic associative network can effectively shield the Na⁺ released by the ionization of sodium PCA, maintaining the stability of the gel morphology, making it suitable for high-salt environments (such as wounds and sweaty skin), and ensuring that the viscosity decrease rate after the addition of sodium PCA is ≤15%, exhibiting good electrolyte resistance stability.

[0019] In this invention, ceramide is prepared into liposomes, which can enhance its solubility and avoid problems such as aggregation and oxidation failure. At the same time, the liposome form can improve transdermal efficiency.

[0020] The hydrogel in this invention is a thin and refreshing type with a viscosity of 5000-12000 mPa·s, providing a comfortable feel on the skin. Furthermore, the transdermal absorption rate of the ceramides in it is high, 3-5 times higher than that of conventional hydrogels. This hydrogel also offers moisturizing, soothing, and repairing effects, making it suitable for sensitive skin care after cosmetic procedures. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of a hydrogel structure;

[0022] Figure 2 This is a schematic diagram of the structure of ceramide NP liposomes. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention; that is, the described embodiments are merely some embodiments of the invention, and not all embodiments.

[0024] Therefore, the following detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0025] It should be noted that relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes the element.

[0026] The features and performance of the present invention will be further described in detail below with reference to the embodiments and accompanying drawings.

[0027] Example 1

[0028] An electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel comprises the following components by weight percentage: 0.5% sodium acrylate copolymer, 0.15% hydrophobically modified ethoxylated polyurethane, 1.2% sodium pyrrolidone carboxylate, 0.3% ceramide NP liposomes, 0.3% ectoine, 0.5% panthenol, 0.1% sodium hyaluronate, 0.4% carboxymethyl dextran, 0.6% phenoxyethanol, 0.3% octyl glycol, and the remainder being deionized water.

[0029] The preparation method of the above-mentioned electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel includes the following steps:

[0030] (1) Add the remaining deionized water to the sterile stirred reactor, control the system temperature at 25°C, turn on the stirring device, set the speed to 60 r / min, and stir at a low speed and uniform speed.

[0031] (2) Maintain a temperature of 25°C and a rotation speed of 60 r / min, slowly sprinkle in sodium hyaluronate and carboxymethyl dextran in batches, and continue stirring for 12 min until the material completely absorbs water and swells, without clumping together, and forms a uniform clear aqueous phase;

[0032] (3) Keep the temperature at 25℃ and the rotation speed at 60r / min, add sodium pyrrolidone carboxylate and panthenol in sequence, stir for 6min until all moisturizing components are completely dissolved and transparent;

[0033] (4) Maintain the temperature at 25°C and adjust the stirring speed to 100 r / min; slowly and evenly add sodium acrylate copolymer, and after fully wetting and dispersing, continue stirring for 15 min; after the material is free of dry powder and evenly dispersed, add hydrophobic modified ethoxylated polyurethane, and stir at the same speed for 18 min to fully swell and crosslink to form a stable thin gel base.

[0034] (5) Preliminary pH adjustment: Slowly add pH adjuster (preferably medical grade citric acid / sodium citrate buffer system) to the gel substrate while stirring at low speed, monitor the pH value in real time, and adjust the pH of the system to 6.0~6.5. Let it stand for 5 minutes to ensure homogeneity;

[0035] (6) Reduce the system temperature to 22°C and the stirring speed to 50 r / min. Under light-protected conditions, add ceramide NP liposomes and ectoin in sequence, and gently stir for 10 min to mix. High-speed shearing is prohibited to avoid liposome rupture and degradation of active ingredients.

[0036] (7) Keep the temperature at 22℃ and the rotation speed at 50r / min, add phenoxyethanol and octyl glycol, and stir for 8min until the system is homogeneous;

[0037] (8) Precise pH control: Add a small amount of pH adjuster again to fine-tune the pH of the system to 5.5~6.0 (medical mild core range), stir for 3 minutes to mix well, and ensure that the pH of the system is stable within the target range;

[0038] (9) Start low-speed homogenization, set the rotation speed to 1800 r / min, homogenize for 1.5 min to refine the texture; then let stand for 25 min to naturally degas, filter through 0.22 μm sterile precision filter, and fill in a sterile environment to obtain the finished product.

[0039] Example 2

[0040] An electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel comprises the following components by weight percentage: 0.4% sodium acrylate copolymer, 0.1% hydrophobically modified ethoxylated polyurethane, 1% sodium pyrrolidone carboxylate, 0.2% ceramide NP liposomes, 0.2% ectoine, 0.4% panthenol, 0.05% sodium hyaluronate, 0.3% carboxymethyl dextran, 0.5% phenoxyethanol, 0.2% octyl glycol, and the balance being deionized water.

[0041] The preparation method of the above-mentioned electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel includes the following steps:

[0042] (1) Add the remaining deionized water to the sterile stirred reactor, control the system temperature at 25°C, turn on the stirring device, set the speed to 60 r / min, and stir at a low speed and uniform speed.

[0043] (2) Maintain a temperature of 25°C and a rotation speed of 60 r / min, slowly sprinkle in sodium hyaluronate and carboxymethyl dextran in batches, and continue stirring for 12 min until the material completely absorbs water and swells, without clumping together, and forms a uniform clear aqueous phase;

[0044] (3) Keep the temperature at 25℃ and the rotation speed at 60r / min, add sodium pyrrolidone carboxylate and panthenol in sequence, stir for 6min until all moisturizing components are completely dissolved and transparent;

[0045] (4) Maintain the temperature at 25°C and adjust the stirring speed to 100 r / min; slowly and evenly add sodium acrylate copolymer, and after fully wetting and dispersing, continue stirring for 12 min; after the material is free of dry powder and evenly dispersed, add hydrophobic modified ethoxylated polyurethane, and stir at the same speed for 15 min to fully swell and crosslink to form a stable thin gel base.

[0046] (5) Preliminary pH adjustment: Slowly add pH adjuster (medical grade citric acid / sodium citrate buffer system) to the gel substrate while stirring at low speed, monitor the pH value in real time, and adjust the pH of the system to 6.0~6.5. Let it stand for 5 minutes to ensure homogeneity;

[0047] (6) Reduce the system temperature to 22°C and the stirring speed to 50 r / min. Under light-protected conditions, add ceramide NP liposomes and ectoin in sequence, and gently stir for 8 min to mix. High-speed shearing is prohibited to avoid liposome rupture and degradation of active ingredients.

[0048] (7) Keep the temperature at 22℃ and the rotation speed at 50r / min, add phenoxyethanol and octyl glycol, and stir for 8min until the system is homogeneous;

[0049] (8) Precise pH control: Add a small amount of pH adjuster again to fine-tune the pH of the system to 5.5~6.0 (medical mild core range), stir for 3 minutes to mix well, and ensure that the pH of the system is stable within the target range;

[0050] (9) Start low-speed homogenization, set the rotation speed to 1800 r / min, homogenize for 1.5 min to refine the texture; then let stand for 25 min to naturally degas, filter through 0.22 μm sterile precision filter, and fill in a sterile environment to obtain the finished product.

[0051] Example 3

[0052] An electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel comprises the following components by weight percentage: 0.6% sodium acrylate copolymer, 0.2% hydrophobically modified ethoxylated polyurethane, 1.5% sodium pyrrolidone carboxylate, 0.4% ceramide NP liposomes, 0.4% ectoine, 0.6% panthenol, 0.15% sodium hyaluronate, 0.5% carboxymethyl dextran, 0.7% phenoxyethanol, 0.4% octyl glycol, and the balance being deionized water.

[0053] The preparation method of the above-mentioned electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel includes the following steps:

[0054] (1) Add the remaining deionized water to the sterile stirred reactor, control the system temperature at 25°C, turn on the stirring device, set the speed to 60 r / min, and stir at a low speed and uniform speed.

[0055] (2) Maintain a temperature of 25°C and a rotation speed of 60 r / min, slowly sprinkle in sodium hyaluronate and carboxymethyl dextran in batches, and continue stirring for 12 min until the material completely absorbs water and swells, without clumping together, and forms a uniform clear aqueous phase;

[0056] (3) Keep the temperature at 25℃ and the rotation speed at 60r / min, add sodium pyrrolidone carboxylate and panthenol in sequence, stir for 6min until all moisturizing components are completely dissolved and transparent;

[0057] (4) Maintain the temperature at 25°C and adjust the stirring speed to 100 r / min; slowly and evenly add sodium acrylate copolymer, and after fully wetting and dispersing, continue stirring for 18 min; after the material is free of dry powder and evenly dispersed, add hydrophobic modified ethoxylated polyurethane, and stir at the same speed for 20 min to fully swell and crosslink to form a stable thin gel base.

[0058] (5) Preliminary pH adjustment: Slowly add pH adjuster (medical grade citric acid / sodium citrate buffer system) to the gel substrate while stirring at low speed, monitor the pH value in real time, and adjust the pH of the system to 6.0~6.5. Let it stand for 5 minutes to ensure homogeneity;

[0059] (6) Reduce the system temperature to 22°C and the stirring speed to 50 r / min. Under light-protected conditions, add ceramide NP liposomes and ectoin in sequence, and gently stir for 12 min to mix. High-speed shearing is prohibited to avoid liposome rupture and degradation of active ingredients.

[0060] (7) Keep the temperature at 22℃ and the rotation speed at 50r / min, add phenoxyethanol and octyl glycol, and stir for 8min until the system is homogeneous;

[0061] (8) Precise pH control: Add a small amount of pH adjuster again to fine-tune the pH of the system to 5.5~6.0 (medical mild core range), stir for 3 minutes to mix well, and ensure that the pH of the system is stable within the target range;

[0062] (9) Start low-speed homogenization, set the rotation speed to 1800 r / min, homogenize for 1.5 min to refine the texture; then let stand for 25 min to naturally degas, filter through 0.22 μm sterile precision filter, and fill in a sterile environment to obtain the finished product.

[0063] Comparative Example 1

[0064] A hydrogel comprising the following components in weight percentage: 0.2% carbomer, 1.2% sodium pyrrolidone carboxylate, 0.3% ceramide NP liposomes, 0.3% ectoine, 0.5% panthenol, 0.1% sodium hyaluronate, 0.4% carboxymethyl dextran, 0.6% phenoxyethanol, 0.3% caprylyl glycol, with the remainder being deionized water.

[0065] The method for preparing the above-mentioned hydrogel includes the following steps:

[0066] (1) Add carbomer to deionized water and stir until completely dissolved to form a gel;

[0067] (2) Add sodium pyrrolidone carboxylate, sodium hyaluronate, carboxymethyl dextran, ectoine, and panthenol, stir evenly, then add ceramide NP liposomes and stir at low speed to disperse;

[0068] (3) Add phenoxyethanol and octyl glycol, stir well, add triethanolamine to adjust the pH to 5.0~6.0, and you will get the product.

[0069] Test case

[0070] 1. Appearance inspection

[0071] Taking the hydrogels prepared in Example 1 and Comparative Example 1 as examples, the prepared hydrogel samples were placed in clean transparent test tubes and their appearance was observed under natural light.

[0072] The results showed that the hydrogel in Example 1 was transparent and uniform, without precipitation or aggregation, and the results were consistent when each sample was observed in triplicate. In contrast, the hydrogel in Comparative Example 1 was cloudy and layered.

[0073] 2. Taking the hydrogels prepared in Example 1 and Comparative Example 1 as examples, the viscosity of the hydrogels was measured.

[0074] (1) Take the prepared hydrogel sample and place it in a constant temperature and humidity chamber at 25℃ for 2 hours to equilibrate. Use a rotational viscometer (NDJ-1 type, rotor No.2, rotation speed 60r / min) to measure the initial viscosity, and record it as η0;

[0075] (2) Add simulated human electrolyte solution (0.9% NaCl solution) to the above hydrogel sample. The amount added is 5% of the mass of the hydrogel. After stirring evenly, equilibrate at a constant temperature of 25℃ for 2 hours. Measure the viscosity at this time and record it as η1.

[0076] (3) Calculate the viscosity decrease rate, viscosity decrease rate = (η0-η1) / η0×100%, each sample is measured in parallel 3 times, and the average value is taken.

[0077] The results showed that after adding the electrolyte solution, the viscosity reduction rate of the hydrogel in Example 1 was between 11.2% and 14.5%, which was less than 15%; while the viscosity reduction rate of the hydrogel in Comparative Example 1 was between 25.4% and 29.2%, with a significant decrease in viscosity.

[0078] 3. Taking the hydrogels prepared in Example 1 and Comparative Example 1 as examples, stability tests were performed.

[0079] (1) Take the prepared hydrogel sample, dispense it into a sealed transparent container, and place it in a 45℃ constant temperature water bath for 30 days;

[0080] (2) During the period, the sample was taken out every 5 days to observe whether its appearance was layered or discolored. The viscosity change was measured by a rotational viscometer and the viscosity was recorded.

[0081] (3) After 30 days, the stability of the sample is judged comprehensively. It is qualified if it meets the requirements of no stratification, no viscosity reduction and no discoloration.

[0082] The results showed that the sample in Example 1 did not separate, decrease in viscosity, or change color after being placed at 45°C for 30 days; while the sample in Comparative Example 1 showed separation, decreased viscosity, and slight turbidity after being placed.

[0083] 4. Transdermal permeability testing

[0084] Taking the hydrogels in Example 1 and Comparative Example 2 as examples, the Franz diffusion cell method was used to detect the transdermal rate using rat abdominal skin (hair removed, subcutaneous fat removed, rinsed with physiological saline, and ready for use) as the transdermal barrier, with 3 parallel samples in each group.

[0085] (1) Fix the rat skin between the supply pool and the receiving pool of the Franz diffusion pool, with the stratum corneum of the skin facing the supply pool. Add physiological saline to the receiving pool as the receiving medium, keep the temperature at 37°C, stir at 300 r / min, and equilibrate for 30 min.

[0086] (2) Add equal amounts of the hydrogel sample (experimental group) and control group hydrogel sample of this application to the supply pool respectively, and take samples from the receiving pool at 1h, 2h, 4h, 6h, 8h, 12h and 24h respectively, while replenishing an equal amount of fresh receiving medium.

[0087] (3) The concentration of ceramide NP in the receiving solution was determined by HPLC, the cumulative transdermal amount was calculated, and then the transdermal rate was calculated.

[0088] The results showed that the transdermal permeability of ceramide in Example 1 was 3 times that of Comparative Example 1.

Claims

1. A thin-film, electrolyte-resistant medical moisturizing and repairing hydrogel, characterized in that, The product comprises the following components by weight percentage: 0.4-0.6% sodium acrylate copolymer, 0.1-0.2% hydrophobically modified ethoxylated polyurethane, 1-1.5% sodium pyrrolidone carboxylate, 0.2-0.4% ceramide NP liposomes, 0.2-0.4% ectoine, 0.4-0.6% panthenol, 0.05-0.15% sodium hyaluronate, 0.3-0.5% carboxymethyl dextran, 0.5-0.7% phenoxyethanol, 0.2-0.4% octyl glycol, and the remainder being deionized water.

2. The electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel as described in claim 1, characterized in that, The composition includes the following components by weight percentage: 0.5% sodium acrylate copolymer, 0.15% hydrophobically modified ethoxylated polyurethane, 1.2% sodium pyrrolidone carboxylate, 0.3% ceramide NP liposomes, 0.3% ectoine, 0.5% panthenol, 0.1% sodium hyaluronate, 0.4% carboxymethyl dextran, 0.6% phenoxyethanol, 0.3% octyl glycol, and the remainder is deionized water.

3. The electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel as described in claim 1, characterized in that, The sodium acrylate copolymer is a copolymer of hydroxyethyl acrylate and sodium acryloyl dimethyl taurate.

4. The electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel as described in claim 1, characterized in that, The particle size of ceramide liposomes is 50-200 nm.

5. The electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel as described in claim 1, characterized in that, Sodium hyaluronate has a molecular weight of less than 100 kDa.

6. The preparation method of the electrolyte-resistant, thin-film medical moisturizing and repairing hydrogel according to any one of claims 1-5, characterized in that, Includes the following steps: (1) Add sodium hyaluronate and carboxymethyl dextran to deionized water in sequence and stir until completely dissolved; (2) Then add sodium pyrrolidone carboxylate and panthenol to it in sequence, and stir until completely dissolved; (3) Continue to add sodium acrylate copolymer to it, stir until there is no dry powder and it is evenly dispersed, then add hydrophobically modified ethoxylated polyurethane, stir until it is fully swollen and crosslinked to form a stable thin gel substrate; (4) Adjust the pH of the gel base to 6.0~6.5, and then add ceramide NP liposomes and ectoine under light-protected conditions. Mix at low speed and continue to adjust the pH to 6.0~6.5, homogenize, defoam, and obtain the finished product.

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