Rapid wound healing dressing and preparation method thereof

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a wound surface rapid healing dressing and a preparation method thereof. The rapid wound healing dressing is prepared from the following components: water, glycerol, sodium carboxymethyl cellulose, calcium alginate and hydrophilic polyurethane, the waterborne polyurethane is prepared from the following raw materials: polyisocyanate, small molecular polyol, polyethylene glycol, polyether polyol, saccharic acid lactone and silicone oil. According to a wet healing idea, water, glycerol, hydroxymethyl cellulose sodium, calcium alginate and hydrophilic polyurethane are effectively combined to prepare a novel functional hydrogel dressing. The product has multiple effects, can be self-adhered, is convenient to cut, is similar to skin color, is light, transparent and attractive in appearance, and facilitates observation of wound healing conditions.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and particularly relates to a wound dressing for rapid healing and a preparation method thereof. Background Art

[0002] Traditional wound dressings include dry gauze and oil gauze. Dry gauze is used to cover wounds, but its exudate management ability is limited, and adhesion to the wound may cause re-injury to the newly formed epithelial tissue; oil gauze dressings contain petrolatum or triglycerides, which can avoid wound adhesion, but have poor ability to promote wound healing. Since the liquid secreted by the wound surface cannot penetrate through the adhesive tape layer, traditional wound dressings are likely to cause local skin soaking, making the wound and the surrounding skin turn white or even rot. Modern wound dressings have largely avoided the drawbacks of traditional wound dressings, and can not only comprehensively protect the wound, but also promote wound healing.

[0003] In recent years, hydrogel-based wound dressings, as multifunctional new dressings, have developed vigorously in the field of medical materials. The main new medical dressings include polyurethane foam and film, composites of water-soluble polymers and rubbers, hydrogels, calcium alginate fibers and fabrics, sodium carboxymethyl cellulose fibers, and various composite dressings. Compared with the previous traditional dressings, hydrogel-based dressings have excellent performance due to their unique high water content rate and superior water retention property, and good physical feeling and unique moisturizing property during the wound healing stage. They have become a hot topic today when people increasingly pursue comfort. However, the current hydrogel-based wound dressings have disadvantages such as poor transparency, poor mechanical properties, and poor water absorption and water content rate. Summary of the Invention

[0004] To solve the above problems, the present invention provides a wound dressing for rapid healing, which comprises the following components: water, glycerol, sodium carboxymethyl cellulose, calcium alginate, and hydrophilic polyurethane.

[0005] Further, the hydrophilic polyurethane is made from the following raw materials: polyisocyanate, small molecule polyol, polyethylene glycol, polyether polyol, sugar lactone, and silicone oil.

[0006] Further, the polyisocyanate includes toluene diisocyanate.

[0007] Further, the small molecule polyol includes glycerol.

[0008] Further, the polyethylene glycol includes PEG600.

[0009] Further, the polyether polyol includes poloxamer L45.

[0010] Further, the sugar acid lactone includes at least one of D-(-)-gulonic acid-γ-lactone, D-galactonic acid lactone, L-galactonic acid-1,4-lactone, and D-galacturonic acid-γ-lactone.

[0011] Further, the weight parts of water in the dressing raw materials are 20 - 50 parts.

[0012] Further, the weight parts of glycerol in the dressing raw materials are 2 - 5 parts.

[0013] Further, the weight parts of sodium carboxymethyl cellulose in the dressing raw materials are 5 - 10 parts.

[0014] Further, the weight parts of calcium alginate in the dressing raw materials are 10 - 15 parts.

[0015] Further, the weight parts of polyisocyanate in the dressing raw materials are 10 - 15 parts.

[0016] Further, the weight parts of small molecule polyol in the dressing raw materials are 5 - 9 parts.

[0017] Further, the weight parts of polyethylene glycol in the dressing raw materials are 20 - 35 parts.

[0018] Further, the weight parts of polyether polyol in the dressing raw materials are 3 - 6 parts.

[0019] Further, the weight parts of sugar acid lactone in the dressing raw materials are 0.5 - 1.5 parts.

[0020] Further, the weight parts of silicone oil in the dressing raw materials are 1 - 2 parts.

[0021] The present invention also provides a preparation method of a wound rapid healing dressing as described herein, which includes the following steps:

[0022] (1) Under nitrogen protection, react polyisocyanate, small molecule polyol, and polyethylene glycol at 80 - 90 °C for 1 - 2 h to obtain a hydrophilic polyurethane prepolymer;

[0023] (2) Disperse polyether polyol, sugar acid lactone, silicone oil, glycerol, sodium carboxymethyl cellulose, and calcium alginate in water, and stir evenly to obtain an aqueous phase mixture;

[0024] (3) Add the hydrophilic polyurethane prepolymer to the aqueous phase mixture at room temperature, stir and mix, then place it in a foaming mold for heat preservation, and demold and cut to obtain the wound rapid healing dressing.

[0025] Further, the polyethylene glycol is dehydrated before use.

[0026] Further, the stirring and mixing in step (3) is carried out at 4000 - 6000 rmp for 10 - 20 s.

[0027] Further, the heat preservation in step (3) is carried out at 60 - 65 °C for 10 - 15 min.

[0028] The present invention also provides the use of the wound rapid healing dressing as described in the present text in the preparation of wound healing materials.

[0029] Beneficial effects of the present invention:

[0030] Based on the concept of moist wound healing, the present invention effectively combines water, glycerol, sodium carboxymethyl cellulose, calcium alginate, and hydrophilic polyurethane to prepare a new type of functional hydrogel dressing. The product has multiple effects, can be self-adhesive, is easy to cut, is similar in color to the skin, has a light and transparent appearance, and is conducive to observing the wound healing situation.

[0031] In order to improve the mechanical properties and water absorption properties of the hydrogel dressing of the present invention, a step-by-step preparation process of prepolymerization (i.e., step (1) of the method of the present invention) and crosslinking (i.e., step (2) of the method of the present invention) is introduced in the process of preparing hydrophilic polyurethane, and gluconolactone is introduced as an auxiliary crosslinking agent in the crosslinking process. It also reacts with isocyanate in the process of polymerizing polyether polyol and isocyanate to obtain crosslinked polyurethane and acts as a crosslinking site in polyurethane. Due to the small molecule characteristics of gluconolactone, it can make the polyurethane crosslinking network more compact, thereby improving the mechanical properties of the hydrogel dressing. At the same time, the high hydrophilicity and polarity of gluconolactone also further improve the water absorption properties of the dressing. Specific embodiments

[0032] The following specific examples are used to further illustrate the present invention, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in the technical field.

[0033] Example 1:

[0034] A wound rapid healing dressing is prepared as follows:

[0035] (1) Add 24 parts by weight of dehydrated PEG600 and 6 parts by weight of glycerol into a three-necked flask equipped with mechanical stirring. After heating to 80 °C under nitrogen protection, add 10 parts by weight of toluene diisocyanate and react under stirring for 1 h (or monitor the -NCO content to reach about 10 wt% by the dibutylamine method) to obtain a hydrophilic polyurethane prepolymer;

[0036] (2) Disperse 4 parts by weight of poloxamer L45, 1 part by weight of D-(-)-guluronic acid-γ-lactone, 1 part by weight of silicone oil L580, 3 parts by weight of glycerol, 6 parts by weight of sodium carboxymethyl cellulose, and 12 parts by weight of calcium alginate in 35 parts by weight of water, and stir evenly to obtain an aqueous phase mixture;

[0037] (3) Add the hydrophilic polyurethane prepolymer obtained in step (1) to the aqueous phase mixture in step (2) at room temperature, stir at 6000 rmp for 10 s, then place it in a foaming mold and keep it warm at 65 °C for 10 min, and obtain the wound rapid healing dressing after demolding and cutting.

[0038] Example 2:

[0039] A wound rapid healing dressing is prepared as follows:

[0040] (1) Add 30 parts by weight of dehydrated PEG600 and 9 parts by weight of glycerol to a three-necked flask equipped with mechanical stirring, heat to 80 °C under nitrogen protection, then add 15 parts by weight of toluene diisocyanate, and react under stirring for 2 h (or monitor the -NCO content to reach about 10 wt% by the dibutylamine method) to obtain a hydrophilic polyurethane prepolymer;

[0041] (2) Disperse 6 parts by weight of poloxamer L45, 1.5 parts by weight of D-(-)-guluronic acid-γ-lactone, 1 part by weight of silicone oil L580, 5 parts by weight of glycerol, 10 parts by weight of sodium carboxymethyl cellulose, and 15 parts by weight of calcium alginate in 20 parts by weight of water, and stir evenly to obtain an aqueous phase mixture;

[0042] (3) Add the hydrophilic polyurethane prepolymer obtained in step 1) to the aqueous phase mixture in step 2) at room temperature, stir at 4500 rmp for 15 s, then place it in a foaming mold and keep it warm at 60 °C for 15 min, and obtain the wound rapid healing dressing after demolding and cutting.

[0043] Example 3:

[0044] Same as Example 1, except that D-(-)-guluronic acid-γ-lactone is replaced with D-galacturonic acid lactone.

[0045] Example 4:

[0046] Same as Example 1, except that the weight fraction of D-(-)-guluronic acid-γ-lactone is adjusted to 0.5 part by weight.

[0047] Example 5:

[0048] Same as Example 1, except that the weight fraction of D-(-)-guluronic acid-γ-lactone is adjusted to 1.5 parts by weight.

[0049] Example 6:

[0050] Same as Example 1, except that the weight fraction of D-(-)-gulonic acid-γ-lactone is adjusted to 2 parts by weight.

[0051] Example 7:

[0052] Same as Example 1, except that the weight fraction of D-(-)-gulonic acid-γ-lactone is adjusted to 3 parts by weight.

[0053] Comparative Example 1:

[0054] Same as Example 1, except that D-(-)-gulonic acid-γ-lactone is not used.

[0055] Comparative Example 2:

[0056] A one-step method is used to prepare the aqueous polyurethane.

[0057] Specifically, 10 parts by weight of toluene diisocyanate, 24 parts by weight of dehydrated PEG600, 6 parts by weight of glycerol, 4 parts by weight of poloxamer L45, 1 part by weight of D-(-)-gulonic acid-γ-lactone, 1 part by weight of silicone oil L580, 3 parts by weight of glycerol, 6 parts by weight of sodium carboxymethylcellulose, 12 parts by weight of calcium alginate, and 35 parts by weight of water are added to a three-necked flask equipped with mechanical stirring. The temperature is raised to 80 °C under nitrogen protection and reacted for 2 h, then placed in a foaming mold and kept at 65 °C for 10 min. After demolding and cutting, a wound rapid healing dressing is obtained.

[0058] Experimental Example 1: Testing the liquid absorption rate and liquid absorption capacity of the wound rapid healing dressing;

[0059] The liquid absorption rate and liquid absorption capacity of the wound rapid healing dressings of Examples 1-7 and Comparative Examples 1-2 are tested, and the results are shown in Table 1:

[0060] Table 1 Test results of liquid absorption rate and liquid absorption capacity

[0061]

[0062]

[0063] As can be seen from the results in Table 1, the liquid absorption amount of Examples 6-7 began to slowly decline, but the liquid absorption rate significantly slowed down, indicating that when the addition amount of glucono delta-lactone is excessive, it will adversely affect the overall water absorption performance of the polyurethane foam. This may be because when the amount of glucono delta-lactone is relatively large, the crosslinking density of the polyurethane is too high, resulting in a slowdown in the water absorption rate. The liquid absorption rate and liquid absorption amount of Comparative Example 1 are significantly inferior to those of Example 1, indicating that the addition of glucono delta-lactone has a significant effect on improving the water absorption performance of the hydrophilic polyurethane foam. From the results of Comparative Example 2, it can be seen that when preparing aqueous polyurethane by the one-pot method, it is difficult to demonstrate the improvement effect of glucono delta-lactone on the performance of hydrophilic polyurethane.

[0064] Experimental Example 2: Wound healing experiment of the wound rapid healing dressing;

[0065] Ninety rabbits with similar body weights and ages were randomly divided into 9 groups, with 10 rabbits in each group. After removing the hair on the back of the rabbits with a depilatory agent, they were anesthetized by intravenous injection of 1% sodium pentobarbital at the ear edge. Under sterile conditions, a cross-shaped wound was made on the skin surface of the depilated area of the rabbits. The wound rapid healing dressings of Examples 1-7 and Comparative Examples 1-2 were successively placed on the wound sites of the rabbits in groups 1-9, and filter paper strips were gently used to blot until the blood no longer oozed out, and the bleeding situation was observed. After 12 h, the polyurethane foam dressing was removed, and the wound condition was recorded. The polyurethane foam dressing was replaced daily for 3 consecutive days. After 3 days, the polyurethane foam dressing was removed, and the wound condition was observed. The results are shown in Table 2:

[0066] Table 2 Wound healing results

[0067] Hemostasis time Wound condition at 12h Wound condition after 3d Example 1 16s No inflammation The wound healed completely, without swelling or redness Example 2 16s No inflammation The wound healed completely, without swelling or redness Example 3 15s No inflammation The wound healed completely, without swelling or redness Example 4 18s No inflammation The wound healed completely, without swelling or redness Example 5 15s No inflammation The wound healed completely, without swelling or redness Example 6 18s No inflammation The wound healed completely, without swelling or redness Example 7 20s Mild inflammation The wound healed basically, without swelling or redness Comparative Example 1 35s Moderate inflammation The wound healed basically, with slight swelling and redness Comparative Example 2 28s Mild inflammation The wound healed basically, without swelling or redness

[0068] As can be seen from Table 1, Examples 1-5 have the performance of rapid healing, the performance of Examples 6-7 has declined, and Comparative Examples 1 and 2 are significantly inferior to Example 1.

[0069] Experimental Example 3: Elastic modulus of the wound rapid healing dressing;

[0070] Under the condition of 25 °C, an oscillatory test was carried out using a rotational rheometer at a strain of 5%, and the elastic modulus value corresponding to a frequency of 1 Hz was taken for comparison. The results are shown in Table 3:

[0071] Table 3 Elastic modulus values

[0072]

[0073]

[0074] The elastic modulus is an index to measure the ease of elastic deformation of a material. The larger the value, the greater the stiffness of the material; the smaller the value, the smaller the stiffness of the material. From the results in Table 3, it can be seen that Examples 1-5 have relatively moderate elastic moduli, Examples 6-7 have too large elastic moduli, and Comparative Examples 1-2 have relatively small elastic moduli.

[0075] It should be noted that the description of the present invention provides preferred embodiments of the present invention. However, the present invention can be implemented in many different forms and is not limited to the embodiments described in this specification. These embodiments do not serve as additional limitations to the content of the present invention. The purpose of providing these embodiments is to make the understanding of the disclosed content of the present invention more thorough and comprehensive. Moreover, the above-mentioned technical features continue to be combined with each other to form various embodiments not listed above, all of which are regarded as within the scope described in the description of the present invention; further, for those of ordinary skill in the art, improvements or transformations can be made according to the above description, and all such improvements and transformations should fall within the protection scope of the appended claims of the present invention.

Claims

1. A wound rapid healing dressing, characterized in that: The raw materials for making the dressing include the following ingredients: water, glycerol, sodium carboxymethyl cellulose, calcium alginate and hydrophilic polyurethane.

2. The rapid wound healing dressing according to claim 1, characterized in that: The hydrophilic polyurethane is prepared from the following raw materials: polyisocyanate, small molecule polyol, polyethylene glycol, polyether polyol, sugar acid lactone and silicone oil.

3. The rapid wound healing dressing according to claim 2, characterized in that: The polyisocyanate includes toluene diisocyanate; the small molecule polyol includes glycerol; the polyethylene glycol includes PEG600; the polyether polyol includes poloxamer L45; The sugar acid lactone includes at least one of D-(-)-gulonic acid-γ-lactone, D-galactonic acid lactone, L-galactonic acid-1,4-lactone, and D-galacturonic acid-γ-lactone.

4. The rapid wound healing dressing according to claim 1, characterized in that: The weight proportion of water in the dressing raw material is 20-50 parts, the weight proportion of glycerin in the dressing raw material is 2-5 parts, the weight proportion of sodium carboxymethyl cellulose in the dressing raw material is 5-10 parts, and the weight proportion of calcium alginate in the dressing raw material is 10-15 parts.

5. The rapid wound healing dressing according to claim 2, characterized in that: The weight proportion of polyisocyanate in the dressing raw material is 10-15 parts, the weight proportion of small molecule polyol in the dressing raw material is 3-5 parts, the weight proportion of polyethylene glycol in the dressing raw material is 20-35 parts, the weight proportion of polyether polyol in the dressing raw material is 3-6 parts, the weight proportion of saccharol lactone in the dressing raw material is 0.5-1.5 parts, and the weight proportion of silicone oil in the dressing raw material is 1-2 parts.

6. A method for preparing a rapid wound healing dressing according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) reacting polyisocyanate, small molecule polyol and polyethylene glycol at 80-90° C. for 1-2 hours under nitrogen protection to obtain a hydrophilic polyurethane prepolymer; (2) dispersing polyether polyol, saccharide lactone, silicone oil, glycerol, sodium carboxymethyl cellulose and calcium alginate in water, and stirring to obtain an aqueous phase mixture; (3) adding the hydrophilic polyurethane prepolymer to the aqueous phase mixture at room temperature, stirring and mixing, placing the mixture in a foaming mold for heat preservation, and demolding and cutting to obtain the rapid wound healing dressing.

7. The preparation method according to claim 6, characterized in that: The polyethylene glycol was dehydrated before use.

8. The preparation method according to claim 6, characterized in that: The stirring and mixing in step (3) is carried out at 4000-6000 rpm for 10-20 seconds.

9. The preparation method according to claim 6, characterized in that: The insulation in step (3) is carried out at 60-65° C. for 10-15 minutes.

10. Use of the rapid wound healing dressing according to any one of claims 1 to 5 in the preparation of wound healing materials.

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