Wound repair spray as well as preparation method and application thereof

Abstract

The invention relates to a wound repair spray, and relates to the field of medical wound repair. The wound repair spray comprises a humectant, ethylhexylglycerin, recombinant collagen, a preservative, a pH buffer agent, water and sodium hyaluronate with the molecular weight of 2000 Da to 10000 Da, and the prepared wound repair spray is fine and soft in atomization effect, uniform and dispersed in spray, moderate in force, suitable for being immediately used after an operation and on sensitive skin, free of toxic and side effects and free of side effects. A good wet healing environment can be provided for wound repair, the healing time of the wound is shortened, and the repair performance is improved.

Description

Technical Field

[0001] The invention belongs to the field of medical wound repair, and more specifically relates to a wound repair spray and a preparation method and use thereof. Background Art

[0002] In recent years, with the changes in dietary structure, air pollution, and the increase in life and work pressure, the number of people with allergies has increased dramatically. The external manifestations of skin sensitivity include: facial capillary dilation and facial flushing related to vascular reaction, skin reactions to specific environmental conditions or contact with certain substances, such as photosensitivity and contact dermatitis. If not treated correctly in time, it will aggravate the skin inflammation reaction and easily cause skin diseases such as dermatitis, eczema, acne, etc. In addition, with the development of science and technology and the improvement of living standards, laser skin care has also shown good results in the treatment of common facial skin diseases. However, in actual application, the thermal effect and photochemical effect of laser will cause different degrees of pain, burning, erythema, and edema to patients, and cause a certain degree of damage to the sebum membrane and stratum corneum on the surface of the skin, forming wounds, and occasionally pigmentation after the scab falls off after laser surgery. If the wound is not properly cared for in time, it is easy to increase the risk of wound infection, pigmentation and scar formation, and ultimately change the patient's appearance, affecting the patient's daily life, work and social activities to a certain extent. It can be seen that wound care is an important auxiliary treatment link throughout the entire treatment process.

[0003] Among the existing wound treatment methods, in addition to conventional drug treatment, various dressings have also become one of the clinical treatment methods. Among them, medical repair spray dressing products are widely used due to their advantages of being easy to carry and use. However, the current research focus on medical repair spray dressing products is mainly on the upgrade and optimization of the formula, and no attention has been paid to the effect of the spray atomization effect on the wound. Therefore, when conventional sprays are sprayed on the wound, the spray dispersion formed is poor, which can easily cause a large impact on the wound, and a tingling sensation is likely to occur during use, which reduces the user experience and is not conducive to the rapid recovery of the wound.

[0004] In view of the problems existing in the prior art, it is urgent to develop a repair spray that has a uniform and soft atomization effect on the basis of good repair performance. Summary of the invention

[0005] In view of the above-mentioned defects and problems of the prior art, the present invention develops a wound repair spray and a preparation method and use thereof.

[0006] The first aspect of the present invention provides a wound repair spray, comprising a moisturizer, ethylhexylglycerin, recombinant collagen, a preservative, a pH buffer, water and sodium hyaluronate with a molecular weight of 2000Da-10000Da; preferably, the molecular weight of the sodium hyaluronate is 3000Da-5000Da.

[0007] In addition to promoting wound healing, recombinant collagen also has a certain moisturizing effect. Sodium hyaluronate has excellent tissue repair function and has good repair and improvement effects on skin damage, skin inflammation and sensitive skin. The coordination between moisturizer, ethylhexylglycerin, recombinant collagen, preservatives, pH buffer, water and sodium hyaluronate with a molecular weight of 3000Da-5000Da can make the surface tension of the prepared wound repair spray smaller. The material sprayed by the conventional nozzle is fine and dense, and is uniform and soft within the spraying range. It is not easy to produce impact and stimulation to the wound, which helps to better apply it to the immediate use of minimally invasive postoperative wounds. Even people with sensitive skin are not likely to feel tingling.

[0008] Optionally, in parts by mass, the moisturizer is 1 to 10 parts, and / or the ethylhexylglycerin is 0.002 to 0.01 parts, and / or the recombinant collagen is 0.01 to 3 parts, and / or the sodium hyaluronate is 0.005 to 1 part.

[0009] Optionally, in parts by mass, the moisturizer is 3 to 8 parts, and / or the ethylhexylglycerol is 0.005 to 0.009 parts, and / or the recombinant collagen is 0.03 to 1 parts, and / or the sodium hyaluronate is 0.05 to 0.3 parts; preferably, the pH buffer comprises 0.002 to 0.003 parts of sodium hydroxide and 0.02 to 0.028 parts of sodium dihydrogen phosphate monohydrate; preferably, the preservative is 0.02 to 0.08 parts; preferably, 0.2 to 0.6 parts of trehalose are also included.

[0010] Optionally, the moisturizer includes 1,3-butanediol; preferably, the preservative is 1,2-hexanediol and / or p-hydroxyacetophenone; preferably, the recombinant collagen is selected from recombinant type III humanized collagen.

[0011] Optionally, a functional component is further included. Preferably, the functional component includes 0.05 to 0.6 parts of ectoine and / or 0.001 to 0.002 parts of bosone by mass.

[0012] Another aspect of the present invention further provides a method for preparing the above-mentioned wound repair spray, comprising the following steps:

[0013] Mixing and stirring the moisturizer and sodium hyaluronate at a temperature of 80 to 100° C. to obtain a first solution;

[0014] Add a preservative, a pH adjuster solution and ethylhexylglycerin to the first solution cooled to 42-48° C., stir, then add the recombinant collagen solution, continue stirring until the material is clear, and discharge the material to obtain the wound repair spray.

[0015] Optionally, during the preparation of the first solution, the stirring speed is 400-600 rpm and the stirring time is 25-50 min.

[0016] Optionally, functional components are further added to the recombinant collagen solution; preferably, the functional components include 0.05-0.6 parts of ectoine and / or 0.001-0.002 parts of bosone, calculated by mass.

[0017] Optionally, the preservative is 1,2-hexanediol and / or p-hydroxyacetophenone; preferably, when the preservative is 1,2-hexanediol and p-hydroxyacetophenone, the 1,2-hexanediol and p-hydroxyacetophenone are first heated and dissolved and then added to the first solution.

[0018] Another aspect of the present invention further provides the use of the wound repair spray in the preparation of cosmetics, skin care products, medicines or medical devices for repairing damaged skin barriers; preferably, the damaged skin barrier is damaged skin barrier after medical aesthetics. Correspondingly, the present invention also provides the use of the wound repair spray for treating damaged skin barriers.

[0019] In summary, this application has the following beneficial effects:

[0020] The wound repair spray of the present invention is compounded with raw materials such as sodium hyaluronate, recombinant collagen, ethylhexylglycerin and moisturizer. The prepared wound repair spray has delicate and soft atomization effect, uniform and dispersed spray, moderate strength, is suitable for immediate use after surgery and on sensitive skin, and has good moisturizing and skin barrier repairing effects, forms an excellent protective film, provides moisture to the wound, provides a good moist healing environment for wound repair, has a more immediate and effective repair effect on the wound, helps shorten the wound healing time, and improves the repair performance. DETAILED DESCRIPTION

[0021] The present application is further described in detail with reference to the following examples. It should be noted that if no specific conditions are specified in the following examples, the conventional conditions or the conditions recommended by the manufacturer are followed, and the raw materials used in the following examples can be obtained from common commercial sources unless otherwise specified.

[0022] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are described in detail below. In the following description, many specific details are set forth to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present application, so the present application is not limited by the specific embodiments disclosed below.

[0023] In this application, "first aspect", "second aspect", "third aspect", etc. are used only for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", "third", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0024] In this application, "optionally", "optional", and "optional" mean optional or dispensable, that is, any one of the two parallel schemes of "yes" or "no". If multiple "options" appear in a technical solution, unless otherwise specified and there is no contradiction or mutual restriction, each "optional" is independent.

[0025] In this application, when it comes to numerical ranges, unless otherwise specified, the above numerical ranges are deemed to be continuous and include the minimum and maximum values ​​of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0026] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0027] Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used in this application and in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application. The term "and / or" used in this application includes any and all combinations of one or more related listed items.

[0028] In order to facilitate the description of the technical solution of this application, the following materials and steps are described before starting the experiment of this application:

[0029] (1) The sources of the main raw materials used in this application are as follows:

[0030] Trehalose: purchased from Shandong Tianli Pharmaceutical Co., Ltd.

[0031] Ethylhexylglycerin, 1,2-hexanediol: purchased from Thor Specialty Chemicals (Zhenjiang) Co., Ltd.

[0032] Recombinant collagen: The recombinant collagen in the present application can be recombinant humanized type I collagen or recombinant humanized type III collagen, both of which are purchased from Jiangsu Yaohai Noxin Biotechnology Co., Ltd. The molecular weights of recombinant humanized type I collagen and recombinant humanized type III collagen are both 30KDa-55KDa.

[0033] Sodium hyaluronate: purchased from Bloomage Biotech Co., Ltd.

[0034] p-Hydroxyacetophenone: purchased from Dezhixin Flavors & Fragrances (Nantong) Co., Ltd.

[0035] Ecdoin: purchased from Bloomage Biotech Co., Ltd.

[0036] Bosine: purchased from Shanghai Keqin Technology Co., Ltd.

[0037] The sources of the various components of the spray container used in the performance test experimental part of this application are as follows:

[0038] The aluminum can was purchased from Shanghai Jiatian Pharmaceutical Packaging Co., Ltd. The inner diameter of the can is 45 mm, the height of the can is 125 mm; the outer diameter of the can mouth is 25.4 mm, and the height of the can mouth is 4.25 mm.

[0039] The actuator, which can be understood as a nozzle, was purchased from the POM series of Apta Packaging Technology (Suzhou) Co., Ltd. The inner diameter of the actuator is 25.4mm and the height is 17.8mm.

[0040] Examples 1-4

[0041] The preparation method is as follows:

[0042] Step 1: Weigh 100g of purified water and add it into a dry and clean beaker 1, weigh 0.4g of trehalose, 1,3-butanediol and sodium hyaluronate with a molecular weight of 3000Da-5000Da and add them into beaker 1, set the heating temperature to 85°C, wait until the temperature reaches (85±2.5)°C, set the speed to 450rpm, keep warm and stir for 30min to obtain the first solution.

[0043] Step 2: Weigh 1,2-hexanediol and p-hydroxyacetophenone into a dry clean beaker 2, heat to 60 (±2.5°C)°C, dissolve, and set aside.

[0044] Step 3: Weigh ethylhexylglycerin into a dry, clean beaker 3.

[0045] Step 4: Weigh sodium hydroxide and sodium dihydrogen phosphate monohydrate into a dry clean beaker 4, add purified water, and dissolve the sodium hydroxide and sodium dihydrogen phosphate monohydrate by adding water while stirring to obtain a pH regulator solution.

[0046] Step 5: Weigh recombinant humanized type III collagen with a molecular weight of 30KDa-55KDa into beaker 5, add purified water to dissolve it to obtain a recombinant collagen solution, add 0.15g of ectoine and 0.0015g of bosone to the recombinant collagen solution to obtain a second solution.

[0047] Step 6: When the temperature of the first solution drops to (45±2.5)°C, add the preservative in step 2, ethylhexylglycerin in step 3, and the pH adjuster solution in step 4 in sequence, stir for 10 minutes, add the second solution in step 5, rinse the materials in beakers 2, 3, 4 and 5 with the remaining reserved water, and pour them into the first solution, continue stirring until the material is clarified, discharge the material, and obtain the wound repair spray.

[0048] The addition amount of each substance in Examples 1-4 is shown in Table 1:

[0049] Table 1. Addition amount of each substance in Examples 1-4 (unit: g)

[0050]

[0051]

[0052] Example 5

[0053] The difference from Example 1 is that trehalose is not added in step 1, and ectoine and bosine are not added to the recombinant collagen solution in step 5.

[0054] Example 6

[0055] The difference from Example 1 is that in step 3, the recombinant humanized type III collagen is replaced with an equal amount of recombinant humanized type I collagen with a molecular weight of 30 KDa-55 KDa.

[0056] It should be noted that in Example 4, 1,2-hexanediol can also be replaced by 1,3-butylene glycol, methylparaben or ethylparaben in an amount that complies with regulations. Since the performance test data of the spray formed by the corresponding products are similar to the performance effect of the product prepared in Example 4, only the data of Example 4 are shown in Tables 2 and 3.

[0057] Comparative Example 1

[0058] The difference from Example 1 is that sodium hyaluronate is not added in step 1.

[0059] Comparative Example 2

[0060] The difference from Example 1 is that ethylhexylglycerin is not added in step six.

[0061] Comparative Example 3

[0062] The difference from Example 1 is that no recombinant humanized type III collagen is added in step six.

[0063] Comparative Example 4

[0064] The difference from Example 1 is that ethylhexylglycerin is not added in step six, and the added amount of sodium hyaluronate is 0.185 g, and the added amount of recombinant type III humanized collagen is 0.085 g.

[0065] Comparative Example 5

[0066] The difference from Example 1 is that ethylhexylglycerin is replaced by an equal amount of phenoxyethanol.

[0067] It should be noted that ethylhexylglycerol can also be replaced here with 1,3-propylene glycol, 1,2-pentanediol or caprylhydroxamic acid in an amount that complies with regulations. Since the performance test data of the spray formed by the corresponding product is similar to the performance effect of the product obtained when ethylhexylglycerol is replaced with an equal amount of phenoxyethanol, Tables 2 and 3 only exemplarily show the data when ethylhexylglycerol is replaced with an equal amount of phenoxyethanol (i.e., Comparative Example 5).

[0068] Comparative Example 6

[0069] The difference from Example 1 is that the molecular weight of sodium hyaluronate is 200,000 Da-400,000 Da.

[0070] Comparative Example 7

[0071] The difference from Example 1 is that the molecular weight of sodium hyaluronate is 500Da-1000Da.

[0072] Performance testing

[0073] Experimental Example 1 Surface tension test

[0074] Surface tension refers to the pulling force between any two adjacent parts of the liquid surface perpendicular to their unit length dividing line. The formation of surface tension is closely related to the special stress state of molecules in the thin layer on the surface of the liquid. For spray, the smaller the surface tension, the better the spraying effect.

[0075] Surface tension test method: Take 10 mL of the samples prepared in Examples 1-6 and Comparative Examples 1-7 as the test samples, and measure the surface tension of each test sample using a surface tension meter.

[0076] The surface tension test results of the samples prepared in Examples 1-6 and Comparative Examples 1-7 are shown in Table 2.

[0077] Experimental Example 2 Spray Angle Test

[0078] The larger the spray angle, the larger the dispersion range. Under the same spray volume, the larger the dispersion range, the better the spray effect.

[0079] Testing method for spray angle: 90 mL of samples prepared in Examples 1-6 and Comparative Examples 1-7 were respectively packed in spray containers of the same model and structure, and the pressing pressure was set to 0.60 MPa as samples to be tested; the samples to be tested were fixed, and the spray nozzle of the samples to be tested was kept pointing straight at the center of a vertical white paper 15 cm away, and the spray button was pressed for 3 seconds according to the set pressure by the machine, and the diameter (d) of the spray pattern on the paper was measured. The spray angle was calculated according to the following formula: θ=2arctan(d / 300).

[0080] The spray angle test results of the samples prepared in Examples 1-6 and Comparative Examples 1-7 are shown in Table 2.

[0081] Experimental Example 3 Spray Particle Size Distribution Test

[0082] Particle size distribution refers to the percentage of particles of different sizes in the total particles. For spray, the more the particle size distribution is concentrated in the small particle size range, the more uniform the spray effect is and the better the atomization effect is.

[0083] Detection method: Use the Malvern Panalytical Spraytec laser diffraction system to measure the particle size distribution of the spray particles in real time. 90mL of the samples prepared in Examples 1-6 and Comparative Examples 1-7 are respectively packed in spray containers of the same model and structure, and the pressing pressure is set to 0.60MPa as the samples to be tested; fix the samples to be tested, and ensure that the center line of the mist beam sprayed by the samples to be tested is perpendicular to the laser beam, and the two laser beams are on the same plane. The nozzle of the test sample is 15cm away from the laser, and the machine presses the spray button according to the set pressure to spray continuously for 5s. Set the test conditions as follows: sampling period: 1s; optical lens: 300mm; refractive index of mist particles: 1.33; dispersion medium: air; refractive coefficient: 1.00.

[0084] The spray particle size distribution test results of the samples prepared in Examples 1-6 and Comparative Examples 1-7 are shown in Table 2.

[0085] Experimental Example 4 Human Trial Test

[0086] The samples prepared in the above Examples 1-6 and Comparative Examples 1-7 were respectively applied to 60 different volunteers, each of whom had non-chronic wound conditions (such as dermatitis eczema, barrier-damaged skin caused by acne, and patients after facial laser / photorejuvenation / acid peeling / micro-plastic surgery).

[0087] Specific operation process: 90mL of samples prepared in Examples 1-6 and Comparative Examples 1-7 are respectively packed in spray containers of the same model and structure as samples to be tested; the samples of Examples 1-6 and Comparative Examples 1-7 are directly sprayed on the cleaned skin. 3-4 times a day, used continuously for 3 days, and observed on the 4th day. Record the satisfaction with the spray effect of the sprays of 1-4 and Comparative Examples 1-7. The specific judgment criteria are as follows: ① Very satisfied: the spray is fine and uniform, the force is gentle, the atomization is good, and there is no sense of water droplets; ② General: the spray atomization effect is poor, the spray on the face is strong, and there is no sense of water droplets; ③ Unsatisfactory: the spray atomization effect is poor, the spray on the face is strong, and there is a sense of water droplets. The results are shown in Table 3.

[0088] Data recording and analysis

[0089] Table 2. Performance test results of samples prepared in Examples 1-6 and Comparative Examples 1-7

[0090]

[0091]

[0092] Table 3. Human trial data

[0093]

[0094] As can be seen from Table 2, the sprays of the samples prepared in Examples 1-6 of the present application are more evenly dispersed, especially the sample prepared in Example 1 has a suitable surface tension, and the spray angle of the spray formed after pressurization is larger, indicating that the spray is more dispersed; the spray particle size is concentrated between 48-54 μm, indicating that the spray particles are relatively small and uniform, which helps to disperse more evenly when forming the spray, and can be softer when contacting the skin. Combined with the data in Table 3, it can be seen that the spray formed by the products prepared in Examples 1-6 for 3 consecutive days can reach a satisfaction rate of more than 95%, and the spray formed by the product prepared in Example 1 is fine and uniform on the skin, with soft force, good atomization, and no water droplet feeling.

[0095] It should be noted that, as can be seen from Example 4, the type of preservative added has little effect on the spraying effect of the sample after it forms a spray.

[0096] When any of sodium hyaluronate, recombinant collagen or ethylhexylglycerin is not added, a uniformly dispersed and soft spray effect cannot be achieved, and when ethylhexylglycerin is not added, even if the amount of sodium hyaluronate and recombinant type III humanized collagen is increased, the effect in Example 1 cannot be achieved. The user's experience of the spray is not very good.

[0097] It should also be noted that when the molecular weight of sodium hyaluronate is too large or too small, it is not conducive to the spray effect of the wound repair spray, and the user's experience of the spray is not very good.

[0098] In addition, the biocompatibility of the wound repair spray prepared in Examples 1-6 was evaluated according to GB / T16886.1-2022 "Biological Evaluation of Medical Devices Part 1: Risk Management Evaluation and Testing":

[0099] 1. The MTT method was used to detect in vitro cytotoxicity, and the test results showed no cytotoxicity.

[0100] 2. Skin irritation test was carried out using rabbit irritation test, and the test results showed that the rabbit irritation reaction was extremely mild.

[0101] 3. The skin sensitization test was conducted using the closed patch method, and the test results were: no skin sensitization reaction.

[0102] 4. The acute toxicity test by skin contact was conducted on mice, and the test results showed that no acute toxic reaction was caused.

[0103] From the biocompatibility experiment, it can be known that the wound repair spray prepared in the present application has no cytotoxic effect, and will not cause skin irritation, skin sensitization and acute toxic reaction. In the normal use process, it will not release toxic substances that are harmful to health, and has good biocompatibility.

[0104] It should be understood that the disclosed invention is not limited only to the specific method, scheme and material of description, because these all can change.It should also be understood that the terminology used herein is only for the purpose of describing specific embodiment scheme, rather than being intended to limit the scope of the present invention, and the scope of the present invention is only limited to the appended claims.

[0105] Those skilled in the art will also recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are also intended to be encompassed by the appended claims.

Claims

1. A wound repair spray, characterized in that: It comprises a moisturizer, ethylhexylglycerin, recombinant collagen, a preservative, a pH buffer, water and sodium hyaluronate with a molecular weight of 2000Da-10000Da; preferably, the molecular weight of the sodium hyaluronate is 3000Da-5000Da.

2. The wound repair spray according to claim 1, characterized in that: In parts by mass, the moisturizer is 1 to 10 parts, and / or the ethylhexylglycerin is 0.002 to 0.01 parts, and / or the recombinant collagen is 0.01 to 3 parts, and / or the sodium hyaluronate is 0.005 to 1 part.

3. The wound repair spray according to claim 2, characterized in that: In parts by mass, the moisturizer is 3 to 8 parts, and / or the ethylhexylglycerol is 0.005 to 0.009 parts, and / or the recombinant collagen is 0.03 to 1 parts, and / or the sodium hyaluronate is 0.05 to 0.3 parts; preferably, the pH buffer comprises 0.002 to 0.003 parts of sodium hydroxide and 0.02 to 0.028 parts of sodium dihydrogen phosphate monohydrate; preferably, the preservative is 0.02 to 0.08 parts; preferably, 0.2 to 0.6 parts of trehalose are also included.

4. The wound repair spray according to claim 3, characterized in that: The moisturizer includes 1,3-butanediol; preferably, the preservative is 1,2-hexanediol and / or p-hydroxyacetophenone; preferably, the recombinant collagen is selected from recombinant type III humanized collagen.

5. The wound repair spray according to claim 1, characterized in that: It also includes functional components. Preferably, the functional components include 0.05-0.6 parts of ectoine and / or 0.001-0.002 parts of bosone by weight.

6. The method for preparing the wound repair spray according to any one of claims 1 to 5, characterized in that: The steps include: Mixing and stirring the moisturizer and sodium hyaluronate at a temperature of 80 to 100° C. to obtain a first solution; Add a preservative, a pH adjuster solution and ethylhexylglycerin to the first solution cooled to 42-48° C., stir, then add the recombinant collagen solution, continue stirring until the material is clear, and discharge the material to obtain the wound repair spray.

7. The method for preparing the wound repair spray according to claim 6, characterized in that: During the preparation of the first solution, the stirring speed is 400-600 rpm and the stirring time is 25-50 min. Preferably, trehalose is also added to the first solution.

8. The method for preparing the wound repair spray according to claim 6, characterized in that: Functional components are also added to the recombinant collagen solution; preferably, the functional components include 0.05-0.6 parts of ectoine and / or 0.001-0.002 parts of bosone, calculated by mass.

9. The method for preparing the wound repair spray according to claim 6, characterized in that: The preservative is 1,2-hexanediol and / or p-hydroxyacetophenone; preferably, when the preservative is 1,2-hexanediol and p-hydroxyacetophenone, the 1,2-hexanediol and p-hydroxyacetophenone are first heated and dissolved, and then added to the first solution.

10. Use of the wound repair spray according to any one of claims 1 to 5 in the preparation of cosmetics, skin care products, medicines or medical devices for repairing damaged skin barrier; preferably, the damaged skin barrier is damaged skin barrier after medical aesthetics.

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