Medical sodium hyaluronate composite solution and preparation method thereof

Abstract

The invention provides a medical sodium hyaluronate composite solution and a preparation method thereof. The sodium hyaluronate composite solution is prepared from the following raw materials in parts by weight: 6 to 8 parts of sodium hyaluronate, 12 to 18 parts of mussel mucoprotein compound, 1.5 to 2 parts of vitamin C ethyl ether, 0.5 to 1.5 parts of sodium chloride and 150 to 160 parts of water for injection. Through the synergistic effect of the sodium hyaluronate, the mussel mucoprotein compound and the vitamin C ethyl ether, a hydrated film protection barrier can be formed on the skin surface in the use process to resist the damage of an external bad environment, a sensitization source, bacteria and the like, meanwhile, a non-chronic micro-wound moist environment can be kept, the moisture loss is slow, and the skin care effect is good. The inflammatory reaction is effectively reduced, secondary inflammation infection of the wound surface is avoided, and migration and growth of cells at the wound can be improved; moreover, part of active substances can permeate into the skin, the moisture content in the skin is maintained, the recovery of the epidermis barrier function is promoted, and the healing of the wound surface is effectively promoted from inside to outside.

Description

Technical Field

[0001] The present invention relates to the technical field of sodium hyaluronate, and in particular to a medical sodium hyaluronate composite solution and a preparation method thereof. Background Art

[0002] With the development of society, people's pursuit of beauty is getting higher and higher, so medical cosmetology has gradually become a popular consumer hotspot for the public, and micro-plastic surgeries such as laser and micro-needle therapy are becoming more and more common. Generally, after micro-plastic surgeries such as laser and micro-needle therapy, sunburn, abrasions, punctures, burns, cuts, etc. on the skin surface will cause damage to the skin barrier, resulting in symptoms of dryness, peeling, redness, swelling, itching, inflammation, etc. Therefore, physical therapy and repair for the above skin discomfort symptoms have become an important research focus.

[0003] At present, the formula of physiotherapy and repair products for the above-mentioned skin discomfort symptoms is relatively simple, mainly composed of sodium hyaluronate, medical preservatives and water for injection. Although it can play a certain role in hydrating and moisturizing, its effect lasts for a short time. In addition, it lacks the function of caring for the skin wound surface, resulting in low cell vitality and migration rate on the wound surface, resulting in prolonged wound repair cycle, and easily leading to secondary infection of the wound surface. Therefore, correct wound care can effectively promote wound healing. Summary of the invention

[0004] In view of this, the present invention provides a medical sodium hyaluronate composite solution and a preparation method thereof.

[0005] The technical solution of the present invention is achieved in this way:

[0006] A medical sodium hyaluronate composite solution comprises the following raw materials in parts by weight: 6-8 parts of sodium hyaluronate, 12-18 parts of mussel mucin complex, 1.5-2 parts of vitamin C ethyl ether, 0.5-1.5 parts of sodium chloride, and 150-160 parts of water for injection; the sodium hyaluronate comprises macromolecular sodium hyaluronate, low-molecular sodium hyaluronate, acetylated sodium hyaluronate, and hydrolyzed sodium hyaluronate in a mass ratio of 5-7:3-4:2-4:2-3.

[0007] Furthermore, the molecular weight of the macromolecular sodium hyaluronate is 1.4 to 1.5 million Da; the molecular weight of the low molecular weight sodium hyaluronate is 400,000 to 500,000 Da.

[0008] Furthermore, the medical sodium hyaluronate composite solution comprises the following raw materials in parts by weight: 8 parts of sodium hyaluronate, 18 parts of mussel mucin complex, 2 parts of vitamin C ethyl ether, 1.2 parts of sodium chloride, and 156 parts of water for injection.

[0009] Furthermore, the mussel mucin complex comprises mussel mucin, quercetin and tremella polysaccharide in a mass ratio of 1:1:2-3.

[0010] Furthermore, the preparation method of the mussel mucin complex is as follows: mussel mucin and purified water are stirred and mixed evenly to obtain a mussel mucin solution; quercetin is added to an ethanol solution and stirred and mixed evenly to obtain a quercetin solution; tremella polysaccharide and purified water are stirred and mixed evenly to obtain a tremella polysaccharide solution; the pH of the mussel mucin solution is adjusted to 5-6.4, the quercetin solution is added dropwise to the mussel mucin solution while stirring and mixing, and then the tremella polysaccharide solution is added and stirred and mixed, and then ultrasonic treatment is performed, centrifuged, and the supernatant is taken and vacuum freeze-dried to powder to obtain the mussel mucin complex.

[0011] Furthermore, the ratio of mussel mucin to purified water is 2 to 5:1 in mg / mL; the ratio of quercetin to ethanol solution is 2 to 5:1 in mg / mL; the mass concentration of the ethanol solution is 60% to 90%; and the ratio of Tremella polysaccharide to purified water is 2 to 5:1 in mg / mL.

[0012] Furthermore, the ultrasonic treatment frequency is 40-60 Hz, the ultrasonic power is 300-500 W, and the ultrasonic time is 15-30 min.

[0013] The preparation method of medical sodium hyaluronate composite solution comprises the following steps: adding water for injection into a stirring tank, adding sodium chloride and stirring and mixing, then adding sodium hyaluronate, heating to 80-85°C and stirring and mixing for 90-120 minutes, cooling to 30-40°C, adding mussel mucin complex and vitamin C ethyl ether and stirring and mixing, and then cooling to 18-28°C and filling to obtain the medical sodium hyaluronate composite solution.

[0014] Furthermore, the stirring speed is 150-200 rpm; the filling temperature is 18° C.-28° C., and the relative humidity is 45%-65%.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The present invention can form a hydration film protection barrier on the skin surface during use through the synergistic effect of sodium hyaluronate, mussel mucin complex and vitamin C ethyl ether to resist damage from adverse external environment, allergens, bacteria and the like, and can also maintain a moist environment for non-chronic minimally invasive wounds, slow down water loss, effectively reduce inflammatory reactions, avoid secondary inflammatory infections of the wound surface, and improve the migration and growth of cells at the wound site; moreover, some active substances can penetrate into the skin, maintain the moisture content in the skin, promote the recovery of the epidermal barrier function, and effectively promote the healing of the wound surface from the inside out.

[0017] The present invention ultrasonically composites mussel mucin, quercetin and tremella polysaccharide when preparing the mussel mucin complex, which can effectively improve the moisture retention performance of the sodium hyaluronate composite solution, maintain the moist environment of the skin, promote the migration of wound cells to repair the wound, improve the wound healing efficiency, delay the release of quercetin, prolong the action time, have good action effect and high stability.

[0018] The sodium hyaluronate composite solution of the present invention can also improve its nursing effect on skin dryness, peeling, redness, swelling, itching, inflammation and other symptoms caused by non-chronic wound conditions such as micro-plastic surgery, sunburn, puncture, scald, cut, etc., and effectively relieve skin discomfort. DETAILED DESCRIPTION

[0019] In order to better understand the technical content of the present invention, specific embodiments are provided below to further illustrate the present invention.

[0020] Unless otherwise specified, the experimental methods used in the embodiments of the present invention are all conventional methods.

[0021] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can be obtained from commercial sources.

[0022] Example 1

[0023] A medical sodium hyaluronate composite solution comprises the following raw materials in parts by weight: 8 parts of sodium hyaluronate, 18 parts of mussel mucin complex, 2 parts of vitamin C ethyl ether, 1.2 parts of sodium chloride, and 156 parts of water for injection; the sodium hyaluronate comprises a macromolecular sodium hyaluronate with a molecular weight of 1.5 million Da, a low molecular weight sodium hyaluronate with a molecular weight of 400,000 Da, acetylated sodium hyaluronate, and hydrolyzed sodium hyaluronate in a mass ratio of 7:3.5:4:2.5;

[0024] Preparation of mussel mucin complex:

[0025] (1) taking mussel mucin, quercetin and tremella polysaccharide in a mass ratio of 1:1:3;

[0026] (2) According to the ratio of mussel mucin to purified water in mg / mL of 2:1, the mussel mucin and purified water were stirred and mixed at a speed of 100 rpm to obtain a mussel mucin solution; according to the ratio of quercetin to ethanol solution with a mass concentration of 80% in mg / mL of 3:1, quercetin was added to the ethanol solution and stirred and mixed at a speed of 100 rpm to obtain a quercetin solution; according to the ratio of Tremella polysaccharide to purified water in mg / mL of 2.5:1, Tremella polysaccharide and purified water were stirred and mixed at a speed of 100 rpm to obtain a quercetin solution; The mixture was stirred and mixed at a speed of 100 rpm to obtain a Tremella polysaccharide solution; the pH of the mussel mucin solution was adjusted to 5.8, the quercetin solution was added dropwise to the mussel mucin solution while stirring at a speed of 100 rpm to mix, and then the Tremella polysaccharide solution was added and stirred for 10 minutes, and then ultrasonic treatment was performed at an ultrasonic power of 500 W for 25 minutes, and the mixture was centrifuged at 3000 r / min for 10 minutes, and the supernatant was vacuum freeze-dried and pulverized to obtain a mussel mucin complex;

[0027] Preparation of medical sodium hyaluronate composite solution:

[0028] Add water for injection into a stirring tank, add sodium chloride and stir at a speed of 180 rpm, keep the stirring speed unchanged, add sodium hyaluronate, heat up to 80° C. and stir for 100 minutes, cool to 30° C., add mussel mucin complex and vitamin C ethyl ether and stir for 70 minutes, cool to 25° C., maintain relative humidity at 50% for filling, and obtain a medical sodium hyaluronate composite solution.

[0029] Example 2

[0030] A medical sodium hyaluronate composite solution comprises the following raw materials in parts by weight: 7 parts of sodium hyaluronate, 15 parts of mussel mucin complex, 1.8 parts of vitamin C ethyl ether, 1.5 parts of sodium chloride, and 160 parts of water for injection; the sodium hyaluronate comprises a macromolecular sodium hyaluronate with a molecular weight of 1.4 million Da, a low molecular weight sodium hyaluronate with a molecular weight of 500,000 Da, acetylated sodium hyaluronate, and hydrolyzed sodium hyaluronate in a mass ratio of 6:3:3:2;

[0031] Preparation of mussel mucin complex:

[0032] (1) taking mussel mucin, quercetin and tremella polysaccharide in a mass ratio of 1:1:2;

[0033] (2) According to the ratio of mussel mucin to purified water mg / mL of 3:1, the mussel mucin and purified water are stirred and mixed at a speed of 90 rpm to obtain a mussel mucin solution; according to the ratio of quercetin to 70% ethanol solution mg / mL of 2.5:1, quercetin is added to the ethanol solution and stirred and mixed at a speed of 90 rpm to obtain a quercetin solution; according to the ratio of Tremella polysaccharide to purified water mg / mL of 4:1, Tremella polysaccharide and purified water are stirred and mixed at a speed of 90 rpm to obtain a Tremella polysaccharide solution; the pH of the mussel mucin solution is adjusted to 6.4, the quercetin solution is added dropwise to the mussel mucin solution at a speed of 90 rpm while stirring and mixing, and then the Tremella polysaccharide solution is added and stirred and mixed, and then ultrasonic treatment is performed at an ultrasonic power of 300 W for 20 min, centrifuged at 3000 r / min for 10 min, and the supernatant is vacuum freeze-dried and pulverized to obtain a mussel mucin complex;

[0034] Preparation of medical sodium hyaluronate composite solution:

[0035] Add water for injection into a stirring tank, add sodium chloride and stir at a speed of 150 rpm, keep the stirring speed unchanged, add sodium hyaluronate, heat up to 80°C, stir and mix for 90 minutes, cool to 40°C, add mussel mucin complex and vitamin C ethyl ether, stir and mix for 90 minutes, cool to 28°C, maintain relative humidity at 65% for filling, and obtain a medical sodium hyaluronate composite solution.

[0036] Example 3

[0037] A medical sodium hyaluronate composite solution comprises the following raw materials in parts by weight: 6 parts of sodium hyaluronate, 12 parts of mussel mucin complex, 1.6 parts of vitamin C ethyl ether, 1.3 parts of sodium chloride, and 150 parts of water for injection; the sodium hyaluronate comprises a macromolecular sodium hyaluronate with a molecular weight of 1.5 million Da, a low molecular weight sodium hyaluronate with a molecular weight of 500,000 Da, acetylated sodium hyaluronate, and hydrolyzed sodium hyaluronate in a mass ratio of 5:4:2:3;

[0038] Preparation of mussel mucin complex:

[0039] (1) taking mussel mucin, quercetin, and tremella polysaccharide in a mass ratio of 1:1:2.5;

[0040] (2) According to the ratio of mussel mucin to purified water mg / mL of 5:1, the mussel mucin and purified water are stirred and mixed at a speed of 100 rpm to obtain a mussel mucin solution; according to the ratio of quercetin to 90% ethanol solution mg / mL of 4:1, quercetin is added to the ethanol solution and stirred and mixed at a speed of 100 rpm to obtain a quercetin solution; according to the ratio of Tremella polysaccharide to purified water mg / mL of 3:1, Tremella polysaccharide and purified water are stirred and mixed at a speed of 100 rpm to obtain a Tremella polysaccharide solution; the pH of the mussel mucin solution is adjusted to 6.0, the quercetin solution is added dropwise to the mussel mucin solution at a speed of 100 rpm while stirring and mixing, and then the Tremella polysaccharide solution is added and stirred and mixed, and then ultrasonic treatment is performed at an ultrasonic power of 400 W for 30 min, centrifuged at 3000 r / min for 10 min, and the supernatant is vacuum freeze-dried and pulverized to obtain a mussel mucin complex;

[0041] Preparation of medical sodium hyaluronate composite solution:

[0042] Add water for injection into a stirring tank, add sodium chloride and stir at a speed of 200 rpm, keep the stirring speed unchanged, add sodium hyaluronate, heat up to 85°C, stir and mix for 120 minutes, cool to 35°C, add mussel mucin complex and vitamin C ethyl ether, stir and mix for 60 minutes, cool to 18°C, maintain relative humidity at 45% for filling, and obtain a medical sodium hyaluronate composite solution.

[0043] Comparative Example 1

[0044] This comparative example does not contain the mussel mucin complex and the vitamin C ethyl ether raw material, and the rest is the same as Example 1.

[0045] The medical sodium hyaluronate composite solution of this comparative example comprises the following raw materials in parts by weight: 8 parts of sodium hyaluronate, 1.2 parts of sodium chloride, and 176 parts of water for injection.

[0046] Preparation of the medical sodium hyaluronate composite solution of this comparative example:

[0047] Add water for injection into a stirring tank, add sodium chloride and stir at a speed of 180 rpm to mix evenly, keep the stirring speed unchanged, add sodium hyaluronate, heat up to 80°C, stir and mix for 100 minutes, then cool to 25°C, maintain the relative humidity at 50% for filling, and obtain a medical sodium hyaluronate composite solution.

[0048] Comparative Example 2

[0049] The sodium hyaluronate in this comparative example only contains macromolecular sodium hyaluronate with a molecular weight of 1.5 million Da, and the rest is the same as that in Example 1.

[0050] The medical sodium hyaluronate composite solution of this comparative example comprises the following raw materials in parts by weight: 8 parts of macromolecular sodium hyaluronate with a molecular weight of 1.5 million Da, 18 parts of mussel mucin complex, 2 parts of vitamin C ethyl ether, 1.2 parts of sodium chloride, and 156 parts of water for injection.

[0051] Comparative Example 3

[0052] In this comparative example, the mussel mucin complex is replaced with a single mussel mucin, and the rest is the same as Example 1.

[0053] The medical sodium hyaluronate composite solution of this comparative example comprises the following raw materials in parts by weight: 8 parts of sodium hyaluronate, 18 parts of mussel mucin, 2 parts of vitamin C ethyl ether, 1.2 parts of sodium chloride, and 156 parts of water for injection; the sodium hyaluronate comprises a macromolecular sodium hyaluronate with a molecular weight of 1.5 million Da, a low molecular weight sodium hyaluronate with a molecular weight of 400,000 Da, acetylated sodium hyaluronate, and hydrolyzed sodium hyaluronate in a mass ratio of 7:3.5:4:2.5;

[0054] Preparation of the medical sodium hyaluronate composite solution of this comparative example:

[0055] Add water for injection into a stirring tank, add sodium chloride and stir at a speed of 180 rpm, keep the stirring speed unchanged, add sodium hyaluronate, heat up to 80° C., stir and mix for 100 minutes, cool to 30° C., add mussel mucin and vitamin C ethyl ether, stir and mix for 70 minutes, cool to 25° C., maintain relative humidity at 50% for filling, and obtain a medical sodium hyaluronate composite solution.

[0056] The sodium hyaluronate composite solutions prepared in the above Examples 1-3 and Comparative Examples 1-3 were tested for moisturizing performance. Ten healthy volunteers aged between 20 and 45 years old, half male and half female (except women in pregnancy or lactation), were selected. The volunteers did not use any moisturizing care products 3 days before the start of the experiment. Before the start of the experiment, the inner forearms of both hands were cleaned and wiped with dry facial tissues. Then, 1-6 sample test areas with an area of ​​2 cm×2 cm were taken from the inner sides of the left and right arms in turn, marked as 1-6, and each area was 1 cm apart. Before applying the sodium hyaluronate composite solution, a skin moisture content tester (Corneometer CM 825) was used to measure the MMV value of the skin stratum corneum moisture content in areas 1-6 as a blank control; 0.04 g of the sodium hyaluronate composite solution of Examples 1-3 and Comparative Examples 1-3 was taken and evenly applied to the sample test areas 1-6 of the left and right arms using latex finger cots, respectively, and the start time of applying the product was recorded. Then, the skin moisture content tester was used to measure the MMV value of the skin stratum corneum moisture content in the sample test area at 4h, 8h and 12h, respectively. The test environment maintained a temperature of 22±1°C and a humidity of 50±5%. Each area was measured 5 times on average, and the experimental results were averaged. The results are shown in Table 1 below.

[0057] Table 1 Changes in moisture content of the stratum corneum of the skin

[0058]

[0059] The above results show that the synergistic effect of sodium hyaluronate, mussel mucin complex and vitamin C ethyl ether of the present invention can better improve the moisture content of the skin and delay the loss of skin moisture, thereby forming a hydration film protective barrier to resist damage from adverse external environments, allergens, bacteria, etc. The effects of Examples 1-3 of the present invention are better than those of Comparative Examples 2-3.

[0060] The effects of the sodium hyaluronate composite solutions prepared in Examples 1-3 of the present invention and Comparative Examples 1-3 on cell migration rates were tested. The determination method is as follows:

[0061] HaCaT keratinocytes (purchased from the Chinese Academy of Sciences) were cultured at 2.5×10 3 Each well was inoculated in a 96-well plate and incubated at 37°C and 5% CO 2 The cells were cultured in a cell culture incubator under the following conditions for 24 hours, and the cells were mechanically scratched using a 96-well cell scratcher. After the scratching, the cells were washed with PBS, and then the dead cells were removed. Fresh EGF-free keratinocyte culture medium was added, and then 50 μL of the sodium hyaluronate composite solution prepared in Example 1-3 and Comparative Example 1-3 with a dilution concentration of 10 mg / mL was added respectively, and photographed and recorded under an inverted microscope. 37°C, 5% CO 2The cells were incubated in an incubator for 24 hours, and photographed again. The migration rate of HaCaT keratinocytes was statistically analyzed using ImageJ software, and the results are shown in Table 2 below.

[0062] Table 2 Effect of sodium hyaluronate complex solution on the migration rate of HaCaT keratinocytes

[0063] HaCaT keratinocyte migration rate / % Example 1 39.17 Example 2 38.96 Example 3 38.65 Comparative Example 1 20.37 Comparative Example 2 35.58 Comparative Example 3 27.86

[0064] The above results show that compared with Example 1, Comparative Example 1 does not contain mussel mucin complex and vitamin C ethyl ether raw materials, resulting in reduced synergy between the raw materials and decreased cell mobility; compared with Example 1, the sodium hyaluronate in Comparative Example 2 only contains a macromolecular sodium hyaluronate with a molecular weight of 1.5 million Da, and the effect is also weakened; Comparative Example 3 replaces the mussel mucin complex with a single mussel mucin, which also affects the cell mobility. It shows that Examples 1-3 of the present invention can significantly improve the cell mobility through the synergistic effect of sodium hyaluronate, mussel mucin complex and vitamin C ethyl ether, thereby effectively promoting the repair of wound cells, promoting the healing of wounds, and shortening the healing time.

[0065] In addition, the sodium hyaluronate composite solution prepared in Examples 1-3 of the present invention was applied to the abraded skin once in the morning and once in the evening, and no purulent or new granulation tissue was found in the abraded wound after use, indicating that the sodium hyaluronate composite solution of the present invention can effectively isolate external pathogens, allergens, etc., avoid wound infection, and promote healing.

[0066] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A medical sodium hyaluronate composite solution, characterized in that: The invention comprises the following raw materials in parts by weight: 6-8 parts of sodium hyaluronate, 12-18 parts of mussel mucin complex, 1.5-2 parts of vitamin C ethyl ether, 0.5-1.5 parts of sodium chloride and 150-160 parts of water for injection; the sodium hyaluronate comprises macromolecular sodium hyaluronate, low molecular sodium hyaluronate, acetylated sodium hyaluronate and hydrolyzed sodium hyaluronate in a mass ratio of 5-7:3-4:2-4:2-3.

2. The medical sodium hyaluronate composite solution according to claim 1, characterized in that: The molecular weight of the macromolecular sodium hyaluronate is 1.4 to 1.5 million Da; the molecular weight of the low-molecular sodium hyaluronate is 400,000 to 500,000 Da.

3. The medical sodium hyaluronate composite solution according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 8 parts of sodium hyaluronate, 18 parts of mussel mucin complex, 2 parts of vitamin C ethyl ether, 1.2 parts of sodium chloride and 156 parts of water for injection.

4. The medical sodium hyaluronate composite solution according to claim 1, characterized in that: The mussel mucin complex comprises mussel mucin, quercetin and tremella polysaccharide in a mass ratio of 1:1:2-3.

5. The medical sodium hyaluronate composite solution according to claim 4, characterized in that: The preparation method of the mussel mucin complex comprises the following steps: stirring and mixing mussel mucin and purified water to obtain a mussel mucin solution; adding quercetin to an ethanol solution and stirring and mixing to obtain a quercetin solution; stirring and mixing tremella polysaccharide and purified water to obtain a tremella polysaccharide solution; adjusting the pH value of the mussel mucin solution to 5-6.4, adding the quercetin solution dropwise to the mussel mucin solution while stirring and mixing, then adding the tremella polysaccharide solution and stirring and mixing, then performing ultrasonic treatment, centrifuging, taking the supernatant and vacuum freeze-drying to powder, and thus obtaining the mussel mucin complex.

6. The medical sodium hyaluronate composite solution according to claim 5, characterized in that: The ratio of mussel mucin to purified water is 2 to 5:1 in mg / mL; the ratio of quercetin to ethanol solution is 2 to 5:1 in mg / mL; the mass concentration of the ethanol solution is 60% to 90%; and the ratio of tremella polysaccharide to purified water is 2 to 5:1 in mg / mL.

7. The medical sodium hyaluronate composite solution according to claim 5, characterized in that: The ultrasonic treatment frequency is 40-60 Hz, the ultrasonic power is 300-500 W, and the ultrasonic time is 15-30 min.

8. The method for preparing the medical sodium hyaluronate composite solution according to any one of claims 1 to 7, characterized in that: The method comprises the following steps: adding water for injection into a stirring tank, adding sodium chloride and stirring and mixing, then adding sodium hyaluronate, heating to 80-85°C, stirring and mixing for 90-120 minutes, cooling to 30-40°C, adding mussel mucin complex and vitamin C ethyl ether, stirring and mixing, and then cooling to 18-28°C for filling to obtain a medical sodium hyaluronate composite solution.

9. The method for preparing the medical sodium hyaluronate composite solution according to claim 8, characterized in that: The stirring speed is 150-200 rpm; the filling temperature is 18° C.-28° C., and the relative humidity is 45%-65%.

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