EGF temperature-sensitive gel and preparation method thereof

Abstract

The invention provides a formula of a temperature-sensitive recombinant human epidermal growth factor hydrogel composition, temperature-sensitive gel takes poloxamer as a drug carrier, and a terminal sterilization mode is filtration sterilization. The temperature-sensitive recombinant human epidermal growth factor hydrogel composition provided by the invention has unique advantages in the aspects of degerming process, temperature sensitivity, stability and practical applicability.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of pharmaceutical preparations, and particularly relates to an EGF temperature-sensitive gel and a preparation method thereof. BACKGROUND

[0002] The recombinant human epidermal growth factor products on the market are roughly divided into external solution, gel and the like.

[0003] The external solution is convenient and flexible to use, generally provided with a spraying device or a dropper, and can be easily sprayed or dripped on the wound surface according to the size and shape of the wound surface, and has a light texture, can be quickly dried to form a protective film after being applied or sprayed on the wound surface, and does not bring obvious heavy or uncomfortable feeling to the patient, and is suitable for irregular shape, large area or difficult to bandage wound surface. The solution can make the recombinant human epidermal growth factor quickly play a role, but compared with some sustained-release dosage forms, the sustained action time of the drug on the wound surface is relatively short, and the drug needs to be given more frequently, which affects the medication compliance of the patient. Moreover, the solution has relatively large fluidity and is easy to lose, and after being applied or sprayed on the wound surface, if the position of the wound surface is not conducive to the drug retention, such as vertical or inclined wound surface, the drug may flow due to gravity, so that the drug cannot fully stay and play a role on the wound surface, and needs to be applied or sprayed multiple times or additional fixing measures are needed. In addition, the solution is more susceptible to environmental influences during use. If the use environment has relatively large humidity or the wound surface has relatively much exudate, the external solution may be diluted, the drug concentration is reduced, and the treatment effect is affected. Moreover, when used on an open wound surface, if the surrounding environment is not clean, the solution may be more susceptible to contamination.

[0004] The gel is an active and attractive carrier, and compared with other semi-solid and liquid preparations, is less greasy, easy to clean, has longer retention time than liquid formula, and is more convenient to use. The gel dosage form can make the recombinant human epidermal growth factor slowly release through the diffusion and dissolution of the matrix, can maintain an effective concentration on the wound surface for a long time, continuously play a drug effect, reduce the frequency of drug use, and improve the medication compliance of the patient. However, due to the relatively thick texture of the gel, the amount of the gel may be relatively difficult to accurately control during application, especially for the case where the drug dosage needs to be strictly controlled, and there may be certain difficulties. If the application skill is not skilled or the wound surface is complex, the gel may not be uniformly applied, resulting in that the drug concentration is too high in part of the wound surface, and the drug coverage is insufficient in part of the wound surface, which affects the treatment effect. In addition, the gel may form a relatively difficult-to-clean film on the wound surface after drying, and is not easy to clean. If not cleaned thoroughly, the residual gel may affect the absorption of the subsequent drug and the observation of the wound surface, and may also cause adverse stimulation to the wound surface.

[0005] In view of the deficiencies of the solution and the general gel in clinical application, there is an urgent need for a high-affinity local drug delivery system.

[0006] Table 1 Differences between gel formulations and traditional skin administration formulations

[0007] SUMMARY

[0008] The present application aims to provide a temperature-sensitive recombinant human epidermal growth factor hydrogel composition prescription, which uses poloxamer as a drug carrier and filtration sterilization as the terminal sterilization method.

[0009] The present application also provides a preparation method of the temperature-sensitive recombinant human epidermal growth factor hydrogel composition.

[0010] Compared with recombinant human epidermal growth factor solution and gel, the temperature-sensitive recombinant human epidermal growth factor hydrogel composition provided by the present application has unique advantages in terms of sterilization process, temperature sensitivity, stability and practical applicability.

[0011] The present application provides a hydrogel composition comprising or prepared from the following raw material components by weight percentage:

[0012] epidermal growth factor 0.001%-0.05%, poloxamer 10%-30%, sodium hyaluronate 0.01%-1.0%, edetate disodium 0.01%-0.8%, albumin 0.005%-0.3%, humectant 0.1-20%, and the balance being water;

[0013] The poloxamer is selected from poloxamer 407 and / or poloxamer 118.

[0014] According to an embodiment of the present application, the epidermal growth factor is recombinant human epidermal growth factor.

[0015] According to an embodiment of the present application, the content of the epidermal growth factor is 0.001%-0.03%, for example 0.001%-0.01%, and exemplary values are 0.001%, 0.0015%, 0.002%, 0.0025%, 0.003%, 0.0035%, 0.004%, 0.0045%, 0.005%, 0.0055%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.015%, 0.02%.

[0016] According to an embodiment of the present application, the content of the poloxamer is 11%-25%, preferably 12%-20%, and exemplary values are 13%, 13.5%, 14%, 14.5%, 14.6%, 14.65%, 14.7%, 14.75%, 15%, 15.5%, 16%, 16.5%, 17%, 17.5%, 18%, 18.5%, 19%, 19.5%, 20%.

[0017] According to an embodiment of the present application, the sodium hyaluronate has a molecular weight of 100KD-800KD, for example 100KD, 150KD, 200KD, 250KD, 300KD, 350KD, 400KD, 450KD, 500KD, 550KD, 600KD, 650KD, 700KD, 750KD, 800KD.

[0018] According to an embodiment of the present application, the sodium hyaluronate has a content of 0.05%-0.8%, for example 0.05%-0.4%, exemplarily 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%.

[0019] According to an embodiment of the present application, the disodium edetate has a content of 0.001%-0.5%, for example 0.005%-0.3%, exemplarily 0.01%, 0.015%, 0.02%, 0.025%, 0.03%, 0.04%, 0.05%, 0.08%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%. According to an embodiment of the present application, the disodium edetate has a content of 0.025%-0.2%, 0.1%.

[0020] According to an embodiment of the present application, the albumin is selected from any one or two of the following: human blood albumin, bovine serum albumin.

[0021] According to an embodiment of the present application, the albumin has a content of 0.005%-0.1%, for example 0.01%-0.04%, exemplarily 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.08%, 0.1%.

[0022] According to an embodiment of the present application, the humectant is selected from any one or two of the following: glycerin, xylitol.

[0023] According to an embodiment of the present application, the humectant has a content of 0.1%-15%, for example 0.1%, 0.3%, 0.5%, 0.8%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, 11%, 12%, 13%, 14%, 15%.

[0024] According to an embodiment of the present application, the hydrogel composition comprises or is prepared from the following raw material components in the following weight percentages:

[0025] Epidermal growth factor 0.001% - 0.03%, poloxamer 12% - 20%, sodium hyaluronate 0.05% - 0.8%, disodium edetate 0.01% - 0.5%, albumin 0.005% - 0.1%, humectant 0.1% - 15%, and the balance being water.

[0026] According to an embodiment of the present application, the hydrogel composition comprises or is prepared from the following raw material components in the following weight percentages:

[0027] Epidermal growth factor 0.002%, poloxamer 14% - 15%, sodium hyaluronate 0.15% - 0.2%, disodium edetate 0.025% - 0.2% or 0.1%, albumin 0.02%, humectant 0.5% - 10%, and the balance being water.

[0028] According to an embodiment of the present application, the hydrogel composition comprises or is prepared from the following raw material components in the following weight percentages: recombinant human epidermal growth factor protein 0.002%, poloxamer 14.65 - 14.75%, sodium hyaluronate 0.15% - 0.2%, disodium edetate 0.025% - 0.2% or 0.1%, human blood albumin 0.02%, glycerin 10%, and the balance being water.

[0029] According to an embodiment of the present application, the hydrogel composition comprises or is prepared from the following raw material components in the following weight percentages: recombinant human epidermal growth factor protein 0.002%, poloxamer 14.65%, sodium hyaluronate 0.2%, disodium edetate 0.025% - 0.2% or 0.1%, human blood albumin 0.02%, glycerin 10%, and the balance being water.

[0030] According to an embodiment of the present application, the hydrogel composition comprises or is prepared from the following raw material components in the following weight percentages: recombinant human epidermal growth factor protein 0.002%, poloxamer 14.75%, sodium hyaluronate 0.15%, disodium edetate 0.025% - 0.2% or 0.1%, human blood albumin 0.02%, glycerin 10%, and the balance being water.

[0031] According to an embodiment of the present application, the hydrogel composition further comprises a pH adjuster.

[0032] According to an embodiment of the present application, the pH adjuster is selected from the group consisting of organic acids, inorganic acids, organic bases, inorganic bases, etc., for example, sodium hydroxide, hydrochloric acid, triethanolamine, etc.

[0033] According to embodiments of the present application, the pH value of the hydrogel composition is 6.5-7.0, preferably 6.6-6.9, for example 6.6, 6.65, 6.7, 6.75, 6.8, 6.85, 6.9, for example 6.7±0.02. According to embodiments of the present application, the pH value of the hydrogel composition can be adjusted by adding an acid or a base to the hydrogel composition. According to embodiments of the present application, the acid is selected from inorganic acids or organic acids, for example hydrochloric acid. According to embodiments of the present application, the base is selected from inorganic bases or organic bases, for example triethanolamine.

[0034] The present application further provides a method for preparing the above-mentioned hydrogel composition, the method comprising the following steps:

[0035] (i) taking disodium edetate, a humectant (for example glycerol), poloxamer and sodium hyaluronate, dissolving in water;

[0036] (ii) adding albumin, epidermal growth factor to the solution in step (i), stirring to uniformity, to obtain the hydrogel composition.

[0037] According to embodiments of the present application, in step (i), take disodium edetate, a humectant (for example glycerol), poloxamer (for example poloxamer 407) and sodium hyaluronate in water, stir, and place in a water bath overnight until the materials are completely dissolved. Preferably, the water bath temperature is 10-20°C, for example 15°C.

[0038] According to embodiments of the present application, step (i) is specifically: taking 70% water, under stirring (stirring speed is 100 rpm-500 rpm, for example 300 rpm), adding disodium edetate, a humectant (for example glycerol), poloxamer and sodium hyaluronate, and placing in a water bath at 15°C overnight until the materials are completely dissolved.

[0039] According to embodiments of the present application, optionally, the pH value of the solution in step (i) is adjusted to 6.6-6.9; for example 6.6, 6.65, 6.7, 6.75, 6.8, 6.85, 6.9, for example 6.7±0.02.

[0040] According to embodiments of the present application, step (ii) is specifically: under stirring (stirring speed is 100 rpm-500 rpm, for example 300 rpm), adding albumin, epidermal growth factor to the solution in step (i), adding water to the full amount, stirring to uniformity, to obtain the hydrogel composition.

[0041] According to embodiments of the present application, optionally, the pH value of the hydrogel composition is adjusted to 6.6-6.9; for example 6.6, 6.65, 6.7, 6.75, 6.8, 6.85, 6.9, for example 6.7±0.02.

[0042] According to the embodiment of the present application, the preparation method is specifically as follows:

[0043] (i) Take 70% of water for injection, under stirring, add the prescribed amount of edetate disodium and humectant (glycerol) to complete dissolution, add the prescribed amount of poloxamer and sodium hyaluronate, and overnight in a water bath until the material is completely dissolved; measure the pH value of the solution, and adjust the pH to 6.7;

[0044] (ii) Keep stirring, add the prescribed amount of albumin to step (i) to be uniform, add the prescribed amount of epidermal growth factor protein solution, and add water to the full amount, stir until uniform, measure the pH value again and adjust the pH to 6.7, and the hydrogel composition is obtained.

[0045] According to the embodiment of the present application, optionally, the hydrogel composition is filtered into a sterilized container using a filter membrane. According to the embodiment of the present application, the sterilization method of the hydrogel composition is filter sterilization.

[0046] The present application also provides a hydrogel composition prepared according to the above preparation method.

[0047] The present application also provides the use of the above hydrogel composition in the preparation of a medicament for treating skin epidermal wounds, abrasions or ulcers.

[0048] Advantages

[0049] Compared with recombinant human epidermal growth factor solution and gel, the temperature-sensitive recombinant human epidermal growth factor hydrogel composition provided by the present application has unique advantages in terms of sterilization process, temperature sensitivity, stability and practicality. DETAILED DESCRIPTION

[0050] The technical solutions of the present application will be further described in detail below in combination with specific examples. It should be understood that the following examples are only illustrative and explanatory of the present application, and should not be interpreted as limiting the scope of protection of the present application. Any technology realized based on the above description of the present application is covered within the scope of protection intended by the present application.

[0051] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0052] Example 1 Preparation of a recombinant human epidermal growth factor hydrogel (Prescription 1)

[0053] (1) Take 70 g of water for injection, under the condition of 300 rpm stirring, add 0.10 g of edetate disodium and 10.0 g of glycerol to completely dissolve, add 14.75 g of poloxamer 407 and 0.15 g of sodium hyaluronate, and completely dissolve the materials in a 15°C water bath overnight.

[0054] (2) Measure the pH value of the solution, and adjust the pH to 6.7±0.02 with triethanolamine.

[0055] (3) Keep the stirring at 300 rpm, add 0.02 g of human serum albumin to the above solution to be uniform, add 2 mg of recombinant human epidermal growth factor protein solution, and add water for injection to 100 g, stir until uniform, measure the pH value again and adjust the pH to 6.7±0.02 with triethanolamine.

[0056] After the content of the preparation solution is qualified, the qualified sample is filtered to a sterilized container using a 0.22 μm filter membrane in a clean bench.

[0057] Preparation of a recombinant human epidermal growth factor hydrogel (Formulation 2)

[0058] (1) Take 70 g of water for injection, under the condition of 300 rpm stirring, add 0.10 g of edetate disodium and 10.0 g of glycerol to completely dissolve, add 14.75 g of poloxamer 407 and 0.15 g of sodium hyaluronate, and completely dissolve the materials in a 15°C water bath overnight.

[0059] (2) Measure the pH value of the solution, and adjust the pH to 6.7±0.02 with triethanolamine.

[0060] (3) Keep the stirring at 300 rpm, add 0.02 g of human serum albumin to the above solution to be uniform, add 2 mg of recombinant human epidermal growth factor protein solution, and add water for injection to 100 g, stir until uniform, measure the pH value again and adjust the pH to 6.7±0.02 with triethanolamine.

[0061] After the content of the preparation solution is qualified, the qualified sample is filtered to a sterilized container using a 0.22 μm filter membrane in a clean bench.

[0062] Preparation of a recombinant human epidermal growth factor hydrogel (Formulation 3-6)

[0063] Formulation 3: The preparation process is the same as Example 2, except that the glycerol content in step (1) is adjusted to 0.5 g.

[0064] Formulation 4: The preparation process is the same as Example 2, except that the edetate disodium content in step (1) is adjusted to 0.2 g.

[0065] Prescription 5: The preparation process is the same as that of Example 2, except that the content of disodium edetate in step (1) is adjusted to 0.05 g.

[0066] Prescription 6: The preparation process is the same as that of Example 2, except that the content of disodium edetate in step (1) is adjusted to 0.025 g.

[0067] Comparative Example

[0068] Comparative Prescription 1: The preparation process is the same as that of Example 2, except that no disodium edetate is added in step (1).

[0069] Comparative Prescription 2: 2 g of sodium hyaluronate is weighed and dissolved in 10 mL of water for injection, and stirred uniformly to obtain a sodium hyaluronate solution; 5 g of poloxamer 407 is weighed and dissolved in 10 mL of water for injection, and left to swell for 24 hours to obtain a poloxamer sol; 0.5 g of glycerol, 0.01 g of potassium sorbate, and 0.002 g of human epidermal growth factor are stirred uniformly in 5 mL of water for injection to obtain an aqueous solution; the aqueous solution containing human epidermal growth factor and the sodium hyaluronate solution are slowly added to the poloxamer sol under stirring, and stirred uniformly to obtain a viscous solution, rather than a hydrogel.

[0070] Comparative Prescription 3: The preparation process is the same as that of Example 2, except that the step of adjusting the pH twice is not included. The pH value of the obtained hydrogel is about 6.0.

[0071] Prescription Stability Study of Example 4

[0072] The recombinant human epidermal growth factor warm-sensitive gel products-prescriptions 1-6 prepared according to the above process in Examples 1-3 are placed at 25°C for 4 weeks, and their stability is investigated, and compared with that of a solution and a comparative prescription. The results are shown in Tables 2-3. Table 2 is the percentage of recombinant human epidermal growth factor protein EGF content of each prescription at 0 days, 1 week, 2 weeks, 3 weeks, and 4 weeks, and Table 3 is the in vitro activity of each prescription at 0 days, 2 weeks, and 4 weeks.

[0073] (1) Determination method of recombinant human epidermal growth factor protein EGF content

[0074] Reagents

[0075]

[0076]

[0077] Alkaline copper test solution: 10 g of sodium hydroxide and 50 g of sodium carbonate are added to 400 mL of water to dissolve, as a methylene solution;

[0078] Take potassium tartrate 0.5 g, add water 50 mL to dissolve, take copper sulfate 0.25 g, add water 30 mL to dissolve, mix the two liquids as the B liquid.

[0079] Before use, combine the A and B liquids, and add water to 500 mL.

[0080] Preparation of the control solution

[0081] Take the serum albumin (bovine) control, dissolve in water and prepare a solution containing 0.2 mg per 1 mL.

[0082] Preparation of the test solution

[0083] Take an appropriate amount of EGF gel sample and diluent (water) and mix in proportion. After mixing and centrifugation, take the supernatant as the test sample. Dilute the test sample to the calibration range, take 0.5 mL of the diluted sample solution, add purified water to 1.0 mL, and determine in the same way.

[0084] Determine according to the Lowry method in the Chinese Pharmacopoeia 2025 Edition Volume IV 0731 Protein Content Determination Method 2.

[0085] (2) In vitro activity determination method

[0086] Reagents

[0087] Name Manufacturer RPMI 1640 medium gibco penicillin / streptomycin gibco bovine serum Hyclone PBS gibco thiazolyl blue (MTT) Sigma dimethyl sulfoxide National Pharmaceutical Group Chemical Reagent Co., Ltd. human epidermal growth factor standard NIBSC BALB / c 3T3 cell strain ATCC

[0088] (1) RPMI 1640 culture solution Take one bag of RPMI 1640 culture medium powder (1 L specification), dissolve and dilute to 1000 mL, add penicillin 10 IU and streptomycin 10 IU, then add sodium bicarbonate 2.1 g, dissolve and mix well, sterilize by filtration, and store at 4℃. 5 5 IU, then add sodium bicarbonate 2.1 g, dissolve and mix well, sterilize by filtration, and store at 4℃.

[0089] (2) Maintenance culture solution Take 4 mL of newborn calf serum, add RPMI 1640 culture solution to 1000 mL.

[0090] (3) Complete culture solution Take 100 mL of newborn calf serum, add RPMI 1640 culture solution to 1000 mL.

[0091] (4) PBS Weigh sodium chloride 8 g, potassium chloride 0.2 g, sodium phosphate dibasic 1.44 g, and potassium phosphate monobasic 0.24 g, dissolve and dilute to 1000 mL with water, and sterilize at 121℃ for 15 minutes.

[0092] (5) Thiazolyl blue (MTT) solution Weigh 0.10 g of MTT powder, add 20 mL of PBS to dissolve, filter sterilize through a 0.22 μm filter membrane. Store at 4℃ in the dark. ​

[0093] Preparation of standard solution

[0094] Take the standard sample of human epidermal growth factor, dilute it with maintenance medium to contain 50 IU per 1 mL according to the instructions. In a 96-well cell culture plate, make a 4-fold serial dilution, a total of 8 dilutions, and 2 holes for each concentration. The above operations are carried out under sterile conditions.

[0095] Preparation of test solution

[0096] Dilute the test sample according to the label, and dilute it with maintenance medium to contain about 50 IU per 1 mL. In a 96-well cell culture plate, make a 4-fold serial dilution, a total of 8 dilutions, and 2 holes for each concentration. The above operations are carried out under sterile conditions.

[0097] According to the method for determining the biological activity of human epidermal growth factor (cell proliferation method / MTT colorimetric method) in Chinese Pharmacopoeia 2025 Edition Volume IV 3528, the determination is carried out.

[0098] Preparation of solution:

[0099] Take 70 mL of water for injection, and add 0.094 g of sodium dihydrogen phosphate monohydrate, 0.437 g of disodium hydrogen phosphate dodecahydrate and 10 g of glycerol under the condition of 300 rpm stirring, and keep until completely dissolved.

[0100] Adjust the pH value of the solution to 7.0 ± 0.2 with 1 mol / L hydrochloric acid or sodium hydroxide solution.

[0101] Under the condition of 300 rpm stirring, add 2 mg of recombinant human epidermal growth factor protein to the above solution, add water for injection to 100 mL, adjust the pH value of the solution to 7.0 ± 0.2 with 1 mol / L hydrochloric acid or sodium hydroxide solution again, and stir for 15 min.

[0102] After the content of the prepared solution is detected and qualified, filter the qualified sample to a sterilized container using a 0.22 μm filter membrane in a clean bench.

[0103] (3) Experimental results

[0104] Table 2 Comparison of stability of each prescription-EGF content percentage

[0105]

[0106]

[0107] According to the content percentage data in Table 2, after 4 weeks of sampling at 25°C, the contents of each comparison batch have different trends. Among them, the EGF content in comparison prescription 1 has a more obvious downward trend, indicating that sodium edetate can effectively protect EGF and improve the stability of EGF in the gel.

[0108] Compared with prescription 2, the EGF content showed a more obvious downward trend, indicating that the stability of the EGF protein in the prescription containing the antibacterial agent was reduced; in addition, the amount of poloxamer added in this comparative example was only 5%, resulting in the prepared sample being a viscous solution rather than a gel, and not having temperature-sensitive properties.

[0109] In Comparative Example 3, the EGF content showed a certain downward trend. When the pH value was not adjusted, the pH value of the gel was about 6.0, which indicated that EGF had better stability in an environment with a pH value of 6.7.

[0110] Table 3 Comparison of stability of various formulations - in vitro activity

[0111]

[0112] According to the in vitro activity data in Table 3, after samples of each batch were stored at 25°C for 4 weeks, the in vitro activity of each comparative batch showed different trends. Among them, the in vitro activity of comparative formula 1 showed the most obvious downward trend, indicating that the addition of edetate disodium can effectively slow down the activity decline. The in vitro activity of comparative formula 2 showed a significant downward trend, indicating that the addition of antibacterial agents exacerbated the decrease in EGF activity. The in vitro activity of comparative formula 3 showed a significant downward trend, indicating that EGF is more stable in an environment with a pH value of 6.7.

[0113] In summary, the addition of disodium edetate can effectively protect EGF and make EGF more stable in the gel; the addition of antibacterial agents reduces the stability of EGF in the gel; EGF is more stable in an environment of pH 6.7.

[0114] From the above experimental results, it can be seen that after the thermosensitive gels of prescriptions 1-6 were placed at 25°C for 4 weeks, the EGF content did not change significantly, the rate of decrease in in vitro activity was slower than that of the solution, and the overall stability was significantly better than that of the solution and the control prescription.

[0115] Thermosensitive gels are temperature-sensitive and typically liquid at lower temperatures. They exhibit good fluidity, making them easy to administer and apply or inject to the desired area. When heated to or slightly above body temperature, they rapidly undergo a phase transition from liquid to gel, forming a stable gel at the site of action. This property allows them to better adapt to the human body's physiological environment.

[0116] This characteristic of forming a gel in situ at body temperature enables it to tightly fill and fit wounds or tissue gaps of various shapes and sizes. Compared with solutions, it will not cause drug loss due to flow. Compared with traditional gels, it can better adapt to irregular wounds, increase the contact area and fit between the drug and the site of action, and thus exert a more effective therapeutic effect.

[0117] The in-situ formed gel state of the temperature-sensitive gel can form a relatively closed environment, which not only prevents the invasion of external bacteria and other microorganisms and reduces the risk of wound infection, but also, compared with common gel agents, the tight gel structure formed at body temperature can be more conducive to blocking the penetration of microorganisms and provides a cleaner environment for wound healing.

[0118] The above describes the embodiments of the present application. However, the present application is not limited to the above-described embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A hydrogel composition comprising or prepared from the following raw material components in the following weight percentages: Epidermal growth factor 0.001%-0.05%, poloxamer 10%-30%, sodium hyaluronate 0.01%-1.0%, edetate disodium 0.01%-0.8%, albumin 0.005%-0.3%, moisturizer 0.1-20%, and the balance is water; The poloxamer is selected from poloxamer 407 and / or poloxamer 118.

2. The hydrogel composition according to claim 1, wherein The epidermal growth factor is recombinant human epidermal growth factor; Preferably, the content of the epidermal growth factor is 0.001%-0.03%; Preferably, the content of the poloxamer is 11%-25%; Preferably, the molecular weight of the sodium hyaluronate is 100KD-800KD; Preferably, the content of sodium hyaluronate is 0.05%-0.8%; Preferably, the content of edetate disodium is 0.01%-0.5%; Preferably, the albumin is selected from any one or two of the following: human serum albumin, bovine serum albumin; Preferably, the albumin content is 0.005%-0.1%; Preferably, the moisturizing agent is selected from any one or two of the following: glycerol, xylitol; Preferably, the content of the moisturizing agent is 0.1%-15%.

3. The hydrogel composition according to claim 1 or 2, characterized in that The hydrogel composition comprises the following raw material components in the following weight percentages or is prepared from the following raw material components: 0.001%-0.03% epidermal growth factor, 12%-20% poloxamer, 0.05%-0.8% sodium hyaluronate, 0.01%-0.5% disodium edetate, 0.005%-0.1% albumin, 0.1%-15% moisturizer, and the balance is water; Preferably, the hydrogel composition comprises the following raw material components in the following weight percentages or is prepared from the following raw material components: epidermal growth factor 0.002%, poloxamer 14%-15%, sodium hyaluronate 0.15%-0.2%, edetate disodium 0.025%-0.2% or 0.1%, albumin 0.02%, moisturizer 0.5%-10%, and the balance is water.

4. The hydrogel composition according to claims 1-3, characterized in that The hydrogel composition comprises the following raw material components in the following weight percentages or is prepared from the following raw material components: 0.002% recombinant human epidermal growth factor protein, 14.65-14.75% poloxamer, 0.15%-0.2% sodium hyaluronate, 0.025%-0.2% or 0.1% disodium edetate, 0.02% human serum albumin, 10% glycerol, and the balance is water; Preferably, the hydrogel composition comprises the following raw material components in the following weight percentages or is prepared from the following raw material components: 0.002% recombinant human epidermal growth factor protein, 14.65% poloxamer, 0.2% sodium hyaluronate, 0.025%-0.2% or 0.1% edetate disodium, 0.02% human serum albumin, 10% glycerol, and the balance is water; Preferably, the hydrogel composition comprises the following raw material components in the following weight percentages or is prepared from the following raw material components: 0.002% recombinant human epidermal growth factor protein, 14.75% poloxamer, 0.15% sodium hyaluronate, 0.025%-0.2% or 0.1% edetate disodium, 0.02% human serum albumin, 10% glycerol, and the balance is water.

5. The hydrogel composition according to claims 1-4, characterized in that The hydrogel composition further includes a pH adjuster; Preferably, the pH adjuster is selected from organic acids, inorganic acids, organic bases, inorganic bases, etc.; Preferably, the pH value of the hydrogel composition is 6.5-7.0, preferably 6.6-6.

9.

6. A method for preparing the hydrogel composition according to any one of claims 1 to 5, comprising the following steps: (i) disodium edetate, moisturizer, poloxamer and sodium hyaluronate are dissolved in water; (ii) adding albumin and epidermal growth factor to the solution in step (i), and stirring evenly to obtain the hydrogel composition.

7. The preparation method according to claim 6, characterized in that In step (i), disodium edetate, a moisturizing agent, poloxamer, and sodium hyaluronate are added to water, stirred, and placed in a water bath overnight until the materials are completely dissolved; preferably, the water bath temperature is 10-20° C.; optionally, the pH value of the solution in step (i) is adjusted to 6.6-6.9; Preferably, step (ii) comprises: adding albumin and epidermal growth factor to the solution in step (i) under stirring, adding water to the total amount, and stirring evenly to obtain the hydrogel composition; optionally, adjusting the pH value of the hydrogel composition to 6.6-6.9; Optionally, filtering the hydrogel composition into a sterilized container using a filter membrane; Preferably, the hydrogel composition is sterilized by filtration.

8. The hydrogel composition prepared by the preparation method according to claim 6 or 7.

9. Use of the hydrogel composition according to any one of claims 1 to 5 in the preparation of a medicament for treating skin epidermal wounds, abrasions or ulcers.

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