Anti-infection ointment for promoting healing of burns and scalds and other wound surfaces and preparation method thereof

Abstract

The invention discloses an anti-infection ointment for promoting healing of burns and scalds and other wound surfaces and a preparation method thereof, the anti-infection ointment comprises active components and auxiliary materials, the active components comprise 0.2-3 parts by weight of ganoderma lucidum chitosan, 0.2-5 parts by weight of recombinant III type collagen, 0.1-2 parts by weight of zinc and 0.5-8 parts by weight of a Cur-Mg compound; the Cur-Mg compound is a compound of Cur-Mg (at) PP hydrogel, antibacterial polyphenol and boric acid ester bond hydrogel. Compared with the prior art, the ointment disclosed by the invention has the advantages of good antibacterial property, high wound healing promoting speed, reduction of scar formation and the like through a synergistic effect of multiple components, and realizes slow release of active components and good wound microenvironment regulation through a hydrogel system.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical technology, and more specifically, relates to an anti-infective ointment for promoting the healing of burn and scald wounds and other wounds, and a preparation method thereof. Background Art

[0002] The healing of burn and scald wounds and other wounds has always been an important topic in the medical field. Burn and scald wounds are prone to infection, the healing process is slow, and scars are easily left after healing, bringing a double burden on the patient's body and mind. Although there are some ointments for the treatment of burns and scalds on the market at present, there are problems such as unsatisfactory antibacterial effects, slow healing promotion speed, and low quality of wound repair. Therefore, it is of great clinical significance to develop an ointment with high-efficiency antibacterial, rapid healing promotion, and scar formation reduction. Summary of the Invention

[0003] The purpose of the present invention is to provide an anti-infective ointment for promoting the healing of burn and scald wounds and other wounds, and a preparation method thereof, which has the characteristics of antibacterial, anti-inflammatory, and promoting tissue repair, and is applicable to the healing of wounds such as burn and scald wounds, surgical incisions, and chronic ulcers.

[0004] The purpose of the present invention can be achieved by the following technical solutions:

[0005] An anti-infective ointment for promoting the healing of burn and scald wounds and other wounds, comprising active ingredients and excipients. In terms of parts by weight, the active ingredients include 0.2 - 3 parts of Ganoderma lucidum chitosan, 0.2 - 5 parts of recombinant type III collagen, 0.1 - 2 parts of zinc, and 0.5 - 8 parts of Cur-Mg complex; the Cur-Mg complex is a Cur-Mg@PP hydrogel, an antibacterial polyphenol, and a borate bond hydrogel complex.

[0006] In this technical solution, the Ganoderma lucidum chitosan has good biocompatibility and antibacterial properties, can promote the healing of wounds, inhibit Staphylococcus aureus and Pseudomonas aeruginosa, activate macrophages to secrete growth factors, and reduce the infl ammatory response. Recombinant type III collagen has the effects of promoting epithelial cell migration, promoting the repair and regeneration of wound tissues, improving the quality of wound healing, and reducing scar formation; and recombinant type III collagen has a synergistic effect with zinc ions, which can promote the proliferation of fibroblasts.

[0007] Furthermore, the zinc is provided by ZnO or zinc gluconate. Zinc is an important trace element, which can participate in DNA synthesis and enzyme catalysis, accelerate the epithelialization process, promote the healing of wounds, enhance immune function, and improve the anti-infection ability of wounds.

[0008] Furthermore, the Cur-Mg@PP hydrogel is a hydrogel formed by the complexation of curcumin (Cur), magnesium ions, and phosphate buffered saline (PBS). Among them, the Cur-Mg@PP hydrogel has good biocompatibility and sustained-release performance, and can continuously release curcumin and magnesium ions to achieve Mg 2+ sustained release, exert antibacterial and anti-inflammatory effects, and accelerate wound closure.

[0009] The antibacterial polyphenol is a polyphenolic compound with antibacterial activity extracted from natural plants, such as tea polyphenols, grape seed extract, etc. It can enhance the antibacterial performance of the ointment and inhibit the growth and reproduction of bacteria on the wound surface.

[0010] The borate bond hydrogel is a hydrogel with self-healing function. It can mimic the self-healing mechanism of human tissues, adsorb bacterial toxins in wound exudate, and form a physical-chemical dual antibacterial barrier with chitosan to promote wound healing.

[0011] Furthermore, the magnesium ions are provided by a magnesium-based material, and the magnesium-based material is MgCl2, MgSO4, or MgO; the molar ratio of curcumin to the magnesium-based material is 1:1-3.

[0012] Furthermore, the phosphate buffered saline (PBS) contains dopamine and poloxamer F127. The proportion of dopamine in the phosphate buffered saline is 0.1-1%, and the proportion of poloxamer in the phosphate buffered saline is 0.5-1.5%. The pH of the phosphate buffered saline is 7.0-7.6.

[0013] Among them, poloxamer F127 has unique thermosensitive properties. It is liquid at low temperatures (such as 4-10°C), and forms a three-dimensional network gel structure when the temperature rises to 25-37°C. Its micelle structure can encapsulate Cur-Mg, and achieve pH-responsive release of active ingredients through a dual mechanism of diffusion and gel degradation. This property makes it an ideal drug sustained-release carrier and can form a drug reservoir locally at the wound surface. In addition, as a non-ionic surfactant, poloxamer F127 promotes the uniform dispersion of curcumin (hydrophobic component) and magnesium ions by reducing the interfacial tension and improves the system stability.

[0014] Furthermore, dopamine forms polydopamine (PDA) through oxidative self-polymerization. On the one hand, polydopamine forms a physical cross-linked network with the polyoxyethylene chain segment of poloxamer F127 through hydrogen bonds, π-π stacking and other interactions, enhancing the mechanical strength of the hydrogel; on the other hand, the catechol group of polydopamine endows the hydrogel with tissue adhesiveness, making it fit more closely to the irregular wound surface; in addition, the phenolic hydroxyl structure of dopamine can disrupt the bacterial biofilm and form multiple antibacterial mechanisms with components such as chitosan and zinc ions.

[0015] The thermosensitive gelation of poloxamer F127 and the dynamic crosslinking with dopamine form a double network structure, which not only ensures fluidity (low-temperature liquid state) but also can rapidly solidify into a gel on the wound surface (triggered by body temperature); the interpenetrating network jointly constructed by the two can increase the swelling rate of the hydrogel, effectively absorb wound exudate, and maintain a moist healing environment.

[0016] Furthermore, the auxiliary materials include an oil-phase matrix and / or a water-phase matrix. The oil-phase matrix includes at least one of petrolatum, liquid paraffin, lanolin, silicone oil, squalane, beeswax, and sesame oil; the water-phase matrix includes at least one of glycerol, propylene glycol, polyethylene glycol, and sodium hyaluronate.

[0017] Furthermore, the active ingredient is dispersed in the water-phase matrix, and the oil-phase matrix is continuously added to the water-phase matrix to form an oil-in-water composition.

[0018] The auxiliary materials also include at least one of an emulsifier, a thickener, a pH regulator, and a preservative. The emulsifier includes at least one of sodium dodecyl sulfate, sodium stearate, Tween-type emulsifiers, Span-type emulsifiers, polyglycerol fatty acid esters, and lecithin; the thickener is at least one of carbomer, xanthan gum, sodium alginate, and hydroxyethyl cellulose.

[0019] A preparation method of an ointment as described above includes the following steps:

[0020] S1: Synthesis of Cur-Mg@PP hydrogel: Mix curcumin with a magnesium-based material, add phosphate buffer saline solution, heat and stir to obtain Cur-Mg@PP hydrogel;

[0021] S2: Preparation of Cur-Mg complex: Mix an antibacterial polyphenol with a borate bond hydrogel, form a composite hydrogel through dynamic crosslinking, and then mix with the Cur-Mg@PP hydrogel prepared in step S1 to obtain a Cur-Mg complex;

[0022] S3: Homogenization of active ingredients: Dissolve Ganoderma lucidum chitosan and recombinant type III collagen, add zinc and the Cur-Mg complex prepared in step S2, and homogenize after mixing;

[0023] S4: pH adjustment and sterilization: Add the remaining auxiliary materials, adjust the pH to 6.0 - 7.0 after mixing, and finally sterilize and package.

[0024] Furthermore, in step S1, the magnesium-based material is MgCl2, MgSO4, or MgO; the phosphate buffer saline solution contains 0.5 - 1.5% poloxamer and 0.1 - 1% dopamine; the temperature condition for heating and stirring is 55 - 65°C; in step S3, the zinc is provided by ZnO or zinc gluconate.

[0025] Beneficial effects of the present invention:

[0026] (1) The ointment of the present invention has the advantages of good antibacterial properties, rapid wound healing, and reduced scar formation through the synergistic effect of multiple components, and realizes the sustained release of active ingredients and good wound microenvironment regulation through the hydrogel system.

[0027] (2) The active ingredients in the ointment of the present invention are all natural or biocompatible materials, have no toxic side effects on the human body, are safe and reliable to use, and are suitable for sensitive wounds. DETAILED DESCRIPTION

[0028] In order to further illustrate the technical means and effects adopted by the present invention to achieve the predetermined purpose of the invention, the specific implementation methods, structures, features and effects of the present invention are described in detail below in combination with the embodiments.

[0029] Example 1

[0030] An anti-infection ointment for promoting the healing of burns, scalds and other wounds, comprising the following components in parts by weight:

[0031]

[0032]

[0033] The preparation method of the above ointment comprises the following steps:

[0034] S1: Synthesis of Cur-Mg@PP hydrogel: Curcumin and MgCl2 were mixed in a 1:2 molar ratio to form a polyphenol-metal complex through magnesium ion coordination. A phosphate buffered saline (PBS) buffer containing 1% poloxamer F127 and 0.5% dopamine was then added. The pH of the phosphate buffered saline was approximately 7.4. The thermosensitivity of the phosphate buffered saline was utilized to assist crosslinking and improve gel stability. The mixture was stirred at a constant temperature of 60°C for 2 hours to promote the micellization of poloxamer and the oxidative polymerization of dopamine, thereby obtaining Cur-Mg@PP hydrogel.

[0035] S2: Preparation of Cur-Mg complex: Antibacterial polyphenols were mixed with borate bond hydrogel to form a composite hydrogel through dynamic crosslinking, and then the Cur-Mg@PP hydrogel prepared in step S1 was added and mixed to obtain a Cur-Mg complex;

[0036] S3: Homogenization of active ingredients: dissolve Ganoderma lucidum chitosan and recombinant type III collagen in deionized water, add zinc oxide and the Cur-Mg complex prepared in step S2, mix and homogenize;

[0037] S4: pH Adjustment and Sterilization: Add the active ingredient obtained in step S3 to the aqueous phase matrix, stir, then add the oil phase matrix and emulsifier to form an oil-in-water type ointment. Finally, adjust the pH to 6.0 - 7.0, sterilize, and package.

[0038] Example 2

[0039] The difference between this example and Example 1 is that in this example, polyethylene glycol 300 is replaced with carbomer to obtain a gel-type ointment.

[0040] Example 3

[0041] The difference between this example and Example 1 is that in this example, the aqueous phase matrix polyethylene glycol 300 is replaced with the oil phase matrix cetyl alcohol to obtain a water-in-oil type ointment.

[0042] Example 4

[0043] The difference between this example and Example 1 is that the ointment in this example includes the following components and parts by weight:

[0044] Function Component Dosage (g) Active ingredient Ganoderma lucidum chitosan 0.2 Active ingredient Recombinant type III collagen 0.2 Active ingredient Zinc oxide 0.1 Active ingredient Cur-Mg complex 0.5 Aqueous phase matrix Glycerol 8.0 Aqueous phase matrix Polyethylene glycol 300 12.0 Oil phase matrix Vaseline 2.5 Emulsifier Tween 80 1.5 Preservative Benzyl alcohol 0.5 Solvent Deionized water To100

[0045] For the specific preparation method, refer to Example 1.

[0046] Example 5

[0047] The difference between this example and Example 1 is that the ointment in this example includes the following components and parts by weight:

[0048]

[0049]

[0050] For the specific preparation method, refer to Example 1.

[0051] Comparative Example 1

[0052] The difference between this comparative example and Example 1 is that in this comparative example, the active ingredient Ganoderma lucidum chitosan is not added.

[0053] Comparative Example 2

[0054] The difference between this comparative example and Example 1 is that in this comparative example, the active ingredient recombinant type III collagen is not added.

[0055] Comparative Example 3

[0056] The difference between this comparative example and Example 1 is that in this comparative example, the active ingredient zinc oxide is not added.

[0057] Comparative Example 4

[0058] The difference between this comparative example and Example 1 is that the active ingredient Cur-Mg complex is not added in this comparative example.

[0059] Comparative Example 5

[0060] The difference between this comparative example and Example 1 is that no Cur-Mg@PP hydrogel is added to the Cur-Mg composite of this comparative example.

[0061] Comparative Example 6

[0062] The difference between this comparative example and Example 1 is that no antibacterial polyphenols are added to the Cur-Mg composite of this comparative example.

[0063] Comparative Example 7

[0064] The difference between this comparative example and Example 1 is that no borate bond hydrogel is added to the Cur-Mg composite of this comparative example.

[0065] Comparative Example 8

[0066] The difference between this comparative example and Example 1 is that the preparation process of this comparative example includes the following steps:

[0067] S1: Synthesis of Cur-Mg@PP hydrogel: Curcumin and MgCl2 were mixed in a 1:2 molar ratio to form a polyphenol-metal complex through magnesium ion coordination. A phosphate buffered saline (PBS) buffer containing 1% poloxamer F127 and 0.5% dopamine was then added. The pH of the phosphate buffered saline was approximately 7.4. The thermosensitivity of the phosphate buffered saline was utilized to assist crosslinking and improve gel stability. The mixture was stirred at a constant temperature of 60°C for 2 hours to promote the micellization of poloxamer and the oxidative polymerization of dopamine, thereby obtaining Cur-Mg@PP hydrogel.

[0068] S2: Homogenization of active ingredients: Cur-Mg@PP hydrogel, antimicrobial polyphenols, borate bond hydrogel, Ganoderma lucidum chitosan, recombinant type III collagen, and zinc oxide were dissolved in deionized water, mixed, and homogenized.

[0069] S3: pH adjustment and sterilization: The active ingredient prepared in step S2 is added to the aqueous phase matrix, and then the oil phase matrix and emulsifier are added after stirring to form an oil-in-water ointment. Finally, the pH is adjusted to 6.0-7.0, and the ointment is sterilized and packaged.

[0070] Comparative Example 9

[0071] The difference between this comparative example and Example 1 is that no active ingredient is added in this comparative example.

[0072] The ointment samples obtained from the above-mentioned examples and comparative examples were numbered. Among them, the ointment samples of Examples 1-5 were numbered 1-5, and the ointment samples of Comparative Examples 1-9 were numbered 6-14.

[0073] Stability test

[0074] The prepared ointments were respectively placed in an incubator at 45 °C, 25 °C and 0 °C for 24 hours, and then taken out to observe whether they were stratified.

[0075] The results showed that except for the ointment sample numbered 13 (Comparative Example 8) which was stratified at 45 °C and 0 °C, the other drug samples were not stratified. This indicated that the samples of the present invention had good stability.

[0076] Pharmacodynamic experiment design

[0077] 1. Seventy adult healthy SD rats were selected and evenly divided into 14 groups, with 5 rats in each group. On the back of each rat, a scald wound with a diameter of 2 cm was established by contacting the skin with an electric heating rod at 100 °C for 3 seconds; in addition, a knife wound with a diameter of 1 cm was established on the leg of the rat. 2 of the scald wound; in addition, a knife wound with a diameter of 1 cm was established on the leg of the rat.

[0078] 2. The ointment samples were applied to the scald wounds and knife wounds of the rats. Among them, each group of rats was correspondingly applied with the ointment samples numbered 1-14, and they were applied once in the morning, middle and evening every day for 7 days, and the improvement of the skin was observed. The improvement of the rats' skin was scored according to the following scoring table.

[0079] Score Skin appearance 0 No redness or swelling, normal skin color, smooth epidermis, normal hair growth 1 Slight redness and swelling, skin color close to normal, slightly raised epidermis, slight hair loss 2 Obvious redness and swelling, significantly reddish skin color, obvious scars, obvious hair loss 3 Severe redness and swelling, accompanied by skin damage and wound infection 4 Skin necrosis or ulcer, severe wound infection

[0080] After scoring each group of rats, the average value was calculated, and the results are shown in Table 1.

[0081] Table 1

[0082]

[0083]

[0084] It can be seen from the test results in Table 1 that compared with Comparative Examples 1-9, the scores of Examples 1-5 were significantly lower, indicating that the ointment of the present invention had the effect of promoting wound healing. Among them, the sample numbered 14 (Comparative Example 9) had no active ingredient and was a blank control cream. Among them, the scores of samples numbered 1 and 2 were lower than those of sample numbered 3, indicating that the oil-in-water type ointment and gel type ointment were better than the water-in-oil type ointment, which might be due to the fact that the oil-in-water type and gel type ointments were more breathable and conducive to wound healing.

[0085] Clinical experiment design

[0086] Thirty patients with first-degree, second-degree, and third-degree burns were selected clinically and evenly divided into three groups. Among them, there were 10 patients with first-degree, second-degree, and third-degree burns in each group. The burn patients in the first group were smeared with the ointment of Example 1 three times a day, the patients in the second group were smeared with commercially available silver sulfadiazine ointment three times a day, and the patients in the third group were smeared with the ointment of Comparative Example 1 three times a day. The healing situation was observed. The results are shown in Table 2.

[0087] Table 2

[0088]

[0089]

[0090] From the above results, it can be seen that the ointment of this example has the beneficial effects of promoting the healing of burn wounds and reducing scar formation.

[0091] The above is only a preferred embodiment of the present invention, and it does not impose any form of limitation on the present invention. Although the present invention has been disclosed above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some changes or modifications to equivalent embodiments by using the above-disclosed technical content within the scope of the technical solution of the present invention. However, as long as it does not depart from the content of the technical solution of the present invention, any brief modification, equivalent change, and modification made to the above embodiments based on the technical essence of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. An anti-infective ointment for promoting the healing of burns, scalds and other wounds, characterized in that, It includes an active ingredient and excipients. By weight, the active ingredient includes 0.2 - 3 parts of Ganoderma lucidum chitosan, 0.2 - 5 parts of recombinant type III collagen, 0.1 - 2 parts of zinc, and 0.5 - 8 parts of Cur-Mg complex; the Cur-Mg complex is a Cur-Mg@PP hydrogel, an antibacterial polyphenol, and a borate bond hydrogel complex.

2. The ointment according to claim 1, characterized in that, The Cur-Mg@PP hydrogel is a hydrogel formed by the complexation of curcumin and magnesium ions with a phosphate buffered saline solution.

3. The ointment according to claim 2, characterized in that, The magnesium ions are provided by a magnesium-based material, and the magnesium-based material is MgCl2, MgSO4, or MgO. The molar ratio of curcumin to the magnesium-based material is 1:1 - 3.

4. The ointment according to claim 2, wherein The phosphate buffered saline solution contains dopamine and poloxamer. The proportion of dopamine in the phosphate buffered saline solution is 0.1 - 1%, and the proportion of poloxamer in the phosphate buffered saline solution is 0.5 - 1.5%.

5. The ointment according to claim 1, characterized in that, The zinc is provided by ZnO or zinc gluconate.

6. The ointment according to claim 1, characterized in that, The excipients include an oil phase matrix and / or a water phase matrix.

7. The ointment according to claim 6, characterized in that, The oil phase matrix includes at least one of petrolatum, liquid paraffin, lanolin, silicone oil, squalane, beeswax, sesame oil, cetyl alcohol, cetostearyl alcohol; the water phase matrix includes at least one of glycerol, propylene glycol, polyethylene glycol, sodium hyaluronate.

8. The ointment according to claim 6, wherein The excipients also include at least one of an emulsifier, a thickener, a pH regulator, a preservative.

9. A method for preparing an ointment according to any one of claims 1 to 8, characterized in that, The preparation method includes the following steps: S1: Synthesis of Cur-Mg@PP hydrogel: Mix curcumin with a magnesium-based material, add a phosphate buffered saline solution, heat and stir to obtain a Cur-Mg@PP hydrogel; S2: Preparation of Cur-Mg complex: Mix an antibacterial polyphenol with a borate bond hydrogel, form a composite hydrogel by dynamic crosslinking, and then add the Cur-Mg@PP hydrogel and mix to obtain a Cur-Mg complex; S3: Homogenization of the active ingredient: Dissolve Ganoderma lucidum chitosan and recombinant type III collagen, add zinc and the Cur-Mg complex prepared in step S2, and homogenize after mixing; S4: pH adjustment and sterilization: Add the remaining excipients, adjust the pH to 6.0 - 7.0 after mixing, and finally sterilize and package.

10. The preparation method according to claim 9, characterized in that, In step S1, the magnesium-based material is MgCl2, MgSO4, or MgO; the phosphate buffered saline solution contains 0.5 - 1.5% poloxamer and 0.1 - 1% dopamine; the temperature condition for heating and stirring is 55 - 65°C; in step S3, the zinc is provided by ZnO or zinc gluconate.

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