Anti-infection ointment for promoting healing of burns, scalds and other wounds and preparation method thereof

Abstract

This invention discloses an anti-infective ointment for promoting the healing of burns, scalds, and other wounds, and its preparation method. The ointment comprises active ingredients and excipients. 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 a Cur-Mg complex. The Cur-Mg complex is a Cur-Mg@PP hydrogel, an antibacterial polyphenol, and a borate ester bond hydrogel complex. Compared with existing technologies, the ointment of this invention, through the synergistic effect of multiple components, has advantages such as good antibacterial properties, rapid wound healing, and reduced scar formation. Furthermore, the hydrogel system enables sustained release of the active ingredients and effective regulation of the wound microenvironment.

Description

Technical Field

[0001] This invention belongs to the technical field of pharmaceutical technology, and more specifically, relates to an anti-infective ointment that promotes the healing of burns and other wounds, and its preparation method. Background Technology

[0002] The healing of burns, scalds, and other wounds has always been an important topic in the medical field. Burn wounds are prone to infection, heal slowly, and often leave scars, placing a double burden on patients both physically and psychologically. While some ointments for treating burns are available on the market, they suffer from problems such as insufficient antibacterial efficacy, slow healing speed, and low quality of wound repair. Therefore, developing an ointment with highly effective antibacterial properties, rapid healing promotion, and reduced scar formation is of significant clinical importance. Summary of the Invention

[0003] The purpose of this invention is to provide an anti-infective ointment that promotes the healing of burns and other wounds, and its preparation method. The ointment has antibacterial, anti-inflammatory, and tissue repair-promoting properties, and is suitable for the healing of burns, surgical incisions, chronic ulcers, and other wounds.

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

[0005] An anti-infective ointment for promoting the healing of burns and other wounds, comprising active ingredients and excipients, wherein, by weight, the active ingredients comprise 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; wherein the Cur-Mg complex is a Cur-Mg@PP hydrogel, an antibacterial polyphenol and a borate ester bond hydrogel complex.

[0006] In this technical solution, the Ganoderma lucidum chitosan possesses excellent biocompatibility and antibacterial properties, promoting wound healing, inhibiting Staphylococcus aureus and Pseudomonas aeruginosa, activating macrophages to secrete growth factors, and reducing inflammatory responses. Recombinant type III collagen promotes epithelial cell migration, wound tissue repair and regeneration, improves wound healing quality, and reduces scar formation; furthermore, recombinant type III collagen has a synergistic effect with zinc ions, promoting fibroblast proliferation.

[0007] Furthermore, the zinc is provided by ZnO or zinc gluconate. Zinc is an important trace element that participates in DNA synthesis and enzyme catalysis, accelerates epithelialization, promotes wound healing, enhances immune function, and improves the wound's resistance to infection.

[0008] Furthermore, the Cur-Mg@PP hydrogel is a hydrogel formed by compounding curcumin (Cur) and magnesium ions with phosphate-buffered saline (PBS). The Cur-Mg@PP hydrogel exhibits good biocompatibility and sustained-release properties, enabling the continuous release of curcumin and magnesium ions, thus achieving the desired magnesium content. 2+ It has a sustained-release effect, exerts antibacterial and anti-inflammatory properties, and accelerates wound closure.

[0009] The antibacterial polyphenols are polyphenolic compounds with antibacterial activity extracted from natural plants, such as tea polyphenols and grape seed extracts. They can enhance the antibacterial properties of the ointment and inhibit the growth and reproduction of bacteria on the wound.

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

[0011] Furthermore, the magnesium ions are provided by a magnesium-based material, which 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, wherein the dopamine content in the PBS is 0.1-1%, and the poloxamer content in the PBS is 0.5-1.5%. The pH of the PBS is 7.0-7.6.

[0013] Poloxamer F127 possesses unique thermosensitive properties. It is liquid at low temperatures (e.g., 4-10℃) and forms a three-dimensional network gel structure when the temperature rises to 25-37℃. Its micellar structure can encapsulate Cur-Mg, achieving pH-responsive release of the active ingredient through a dual mechanism of diffusion and gel degradation. This characteristic makes it an ideal drug sustained-release carrier, forming a drug reservoir locally at the wound site. Furthermore, as a nonionic surfactant, poloxamer F127 improves system stability by reducing interfacial tension and promoting the uniform dispersion of curcumin (a hydrophobic component) and magnesium ions.

[0014] Furthermore, dopamine undergoes oxidative self-polymerization to form polydopamine (PDA). On one hand, PDA and the polyoxyethylene segments of poloxamer F127 form a physical cross-linking network through hydrogen bonding, π-π stacking, and other interactions, enhancing the mechanical strength of the hydrogel. On the other hand, the catechol groups of PDA impart tissue adhesion to the hydrogel, allowing it to adhere more closely to irregular wound surfaces. In addition, the phenolic hydroxyl structure of dopamine can disrupt bacterial biofilms and form multiple antibacterial mechanisms with components such as chitosan and zinc ions.

[0015] The thermosensitive gelation of poloxamer F127 and the dynamic cross-linking of dopamine form a dual network structure, which ensures both fluidity (low-temperature liquid state) and rapid gelation on the wound surface (body temperature triggered); the interpenetrating network constructed by the two can improve the swelling rate of the hydrogel, effectively absorb wound exudate, and maintain a moist healing environment.

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

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

[0018] The excipients also include at least one of emulsifiers, thickeners, pH adjusters, and preservatives. The emulsifiers include at least one of sodium dodecyl sulfate, sodium stearate, Tween-type emulsifiers, Span-type emulsifiers, polyglycerol fatty acid esters, and lecithin; the thickeners are at least one of carbomer, xanthan gum, sodium alginate, and hydroxyethyl cellulose.

[0019] A method for preparing the ointment as described above includes the following steps:

[0020] S1: Synthesis of Cur-Mg@PP hydrogel: Curcumin was mixed with magnesium-based materials, phosphate buffer solution was added, and the mixture was heated and stirred to obtain Cur-Mg@PP hydrogel;

[0021] S2: Preparation of Cur-Mg complex: Antibacterial polyphenols are mixed with borate ester hydrogels and formed into composite hydrogels through dynamic cross-linking. Then, the Cur-Mg@PP hydrogels prepared in step S1 are added and mixed to obtain the 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 obtained in step S2, mix and homogenize;

[0023] S4: pH adjustment and sterilization: Add the remaining excipients, mix, adjust the pH to 6.0-7.0, and finally sterilize and dispense.

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

[0025] The beneficial effects of this invention are:

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

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

[0028] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with embodiments, is provided below.

[0029] Example 1

[0030] An anti-infective ointment that promotes the healing of burns and other wounds, comprising the following components and parts by weight:

[0031]

[0032]

[0033] The preparation method of the above-mentioned ointment includes the following steps:

[0034] S1: Synthesis of Cur-Mg@PP hydrogel: Curcumin and MgCl2 were mixed at a molar ratio of 1:2 to form a polyphenol-metal complex through magnesium ion coordination. Then, a phosphate buffer solution containing 1% poloxamer F127 and 0.5% dopamine was added to the PBS buffer solution, where the pH of the PBS buffer solution was about 7.4. The thermosensitive nature of the PBS buffer solution was used to assist cross-linking and improve the stability of the gel. The mixture was stirred at 60°C for 2 hours to promote the micellization of poloxamer and the oxidative polymerization of dopamine, thus obtaining the Cur-Mg@PP hydrogel.

[0035] S2: Preparation of Cur-Mg complex: Antibacterial polyphenols are mixed with borate ester hydrogels and formed into composite hydrogels through dynamic cross-linking. Then, the Cur-Mg@PP hydrogels prepared in step S1 are added and mixed to obtain the Cur-Mg complex.

[0036] S3: Homogenization of active ingredients: Ganoderma lucidum chitosan and recombinant type III collagen were dissolved in deionized water, and zinc oxide and the Cur-Mg complex obtained in step S2 were added. After mixing, the mixture was homogenized.

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

[0038] Example 2

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

[0040] Example 3

[0041] The difference between this embodiment and Embodiment 1 is that the aqueous matrix polyethylene glycol 300 is replaced with the oil matrix hexadecyl alcohol to prepare a water-in-oil ointment.

[0042] Example 4

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

[0044] Function Components Dosage (g) Active ingredients Ganoderma chitosan 0.2 Active ingredients Recombinant type III collagen 0.2 Active ingredients Zinc oxide 0.1 Active ingredients Cur-Mg complex 0.5 Aqueous matrix glycerin 8.0 Aqueous matrix Polyethylene glycol 300 12.0 oil phase matrix Vaseline 2.5 emulsifier Twain 80 1.5 preservative benzyl alcohol 0.5 solvent Deionized water To100

[0045] For specific preparation methods, please refer to Example 1.

[0046] Example 5

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

[0048]

[0049]

[0050] For specific preparation methods, please refer to Example 1.

[0051] Comparative Example 1

[0052] The difference between this comparative example and Example 1 is that no active ingredient, Ganoderma lucidum chitosan, was added in this comparative example.

[0053] Comparative Example 2

[0054] The difference between this comparative example and Example 1 is that no active ingredient, recombinant type III collagen, was added to this comparative example.

[0055] Comparative Example 3

[0056] The difference between this comparative example and Example 1 is that no active ingredient, zinc oxide, was added in this comparative example.

[0057] Comparative Example 4

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

[0059] Comparative Example 5

[0060] The difference between this comparative example and Example 1 is that the Cur-Mg complex in this comparative example does not contain Cur-Mg@PP hydrogel.

[0061] Comparative Example 6

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

[0063] Comparative Example 7

[0064] The difference between this comparative example and Example 1 is that no borate ester hydrogel was added to the Cur-Mg complex in 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 at a molar ratio of 1:2 to form a polyphenol-metal complex through magnesium ion coordination. Then, a phosphate buffer solution containing 1% poloxamer F127 and 0.5% dopamine was added to the PBS buffer solution, where the pH of the PBS buffer solution was about 7.4. The thermosensitive nature of the PBS buffer solution was used to assist cross-linking and improve the stability of the gel. The mixture was stirred at 60°C for 2 hours to promote the micellization of poloxamer and the oxidative polymerization of dopamine, thus obtaining the Cur-Mg@PP hydrogel.

[0068] S2: Homogenization of active ingredients: Dissolve Cur-Mg@PP hydrogel, antibacterial polyphenols, borate ester bond hydrogel, Ganoderma lucidum chitosan, recombinant type III collagen, and zinc oxide in deionized water, mix and homogenize.

[0069] S3: pH adjustment and sterilization: Add the active ingredient obtained in step S2 to the aqueous matrix, stir, then add the oil matrix and emulsifier to form an oil-in-water ointment. Finally, adjust the pH to 6.0-7.0, sterilize and package.

[0070] Comparative Example 9

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

[0072] The ointment samples obtained in the above embodiments and comparative examples were numbered, with the ointment samples of Examples 1-5 numbered 1-5 and the ointment samples of Comparative Examples 1-9 numbered 6-14.

[0073] Stability test

[0074] After storing the prepared ointment in constant temperature incubators at 45℃, 25℃ and 0℃ for 24 hours, remove it and observe whether it separates into layers.

[0075] The results showed that, except for the ointment sample No. 13 (Comparative Example 8), which separated into layers at 45°C and 0°C, the other drug samples did not separate into layers. This indicates that the samples of the present invention have good stability.

[0076] Pharmacodynamic experimental design

[0077] 1. Seventy healthy adult SD rats were selected and divided into 14 groups of 5 rats each. A 2cm diameter incision was created on the back of each rat by applying a 100℃ heating rod to the skin for 3 seconds. 2 Burn wounds were created on rats; additionally, 1 cm diameter knife wounds were created on the legs of rats.

[0078] 2. Apply ointment samples to the burn and cut wounds of rats. Each group of rats was treated with ointment samples numbered 1-14, applied three times daily (morning, noon, and evening) for 7 days. Observe the skin improvement. Assess the rats' skin improvement using the scoring table below.

[0079] Score Skin appearance 0 No redness or swelling, normal skin color, smooth skin, and normal hair growth. 1 Slight redness and swelling, skin color close to normal, slight skin bulge, and slight hair loss. 2 There is obvious redness and swelling, the skin tone is noticeably reddish, there are obvious scars, and there is obvious hair loss. 3 Severe redness and swelling, accompanied by skin lesions and wound infection. 4 Skin necrosis or ulceration, severe wound infection

[0080] The average score was calculated for each group of rats, and the results are shown in Table 1.

[0081] Table 1

[0082]

[0083]

[0084] As shown in Table 1, the scores of Examples 1-5 were significantly lower than those of Comparative Examples 1-9, indicating that the ointment of the present invention has the effect of promoting wound healing. Example 14 (Comparative Example 9) contained no active ingredient and served as a blank control cream. The scores of Examples 1 and 2 were lower than those of Example 3, indicating that water-in-oil and gel-type ointments are better than oil-in-water ointments. This may be because water-in-oil and gel-type ointments are more breathable, which is beneficial for wound healing.

[0085] Clinical trial design

[0086] Thirty patients each of first-degree, second-degree, and third-degree burns were selected and randomly divided into three groups, with 10 patients in each group. The first group applied the ointment from Example 1 three times daily; the second group applied commercially available silver sulfadiazine ointment three times daily; and the third group applied the ointment from Comparative Example 1 three times daily. Healing was observed. The results are shown in Table 2.

[0087] Table 2

[0088]

[0089]

[0090] The results above show that the ointment in this embodiment has the beneficial effects of promoting the healing of burn wounds and reducing scar formation.

[0091] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. An anti-infective ointment that promotes the healing of burns, scalds, and other wounds, characterized in that, The product includes active ingredients and excipients. 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 ester bond hydrogel complex. The Cur-Mg@PP hydrogel is a hydrogel formed by combining curcumin and magnesium ions with phosphate buffer solution. The excipients include an oil-phase matrix and / or an aqueous-phase matrix.

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

3. The ointment according to claim 1, characterized in that, The phosphate buffer solution contains dopamine and poloxamer, wherein the dopamine content in the phosphate buffer solution is 0.1-1%, and the poloxamer content in the phosphate buffer solution is 0.5-1.5%.

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

5. The ointment according to claim 1, characterized in that, The oil phase matrix includes at least one of petrolatum, liquid paraffin, lanolin, silicone oil, squalane, beeswax, sesame oil, cetyl alcohol, and cetearyl alcohol; the aqueous phase matrix includes at least one of glycerin, propylene glycol, polyethylene glycol, and sodium hyaluronate.

6. The ointment according to claim 1, characterized in that, The excipients also include at least one of emulsifiers, thickeners, pH adjusters, and preservatives.

7. A method for preparing an ointment as described in any one of claims 1-6, characterized in that, The preparation method includes the following steps: S1: Synthesis of Cur-Mg@PP hydrogel: Curcumin was mixed with magnesium-based materials, phosphate buffer solution was added, and the mixture was heated and stirred to obtain Cur-Mg@PP hydrogel; S2: Preparation of Cur-Mg complex: Antibacterial polyphenols are mixed with borate ester hydrogels and formed into composite hydrogels through dynamic cross-linking. Then, Cur-Mg@PP hydrogels are added and mixed to obtain the Cur-Mg complex. S3: Homogenization of active ingredients: Dissolve Ganoderma lucidum chitosan and recombinant type III collagen, add zinc and the Cur-Mg complex obtained in step S2, mix and homogenize; S4: pH adjustment and sterilization: Add the remaining excipients, mix, adjust the pH to 6.0-7.0, and finally sterilize and dispense.

8. The preparation method according to claim 7, characterized in that, In step S1, the magnesium-based material is MgCl2, MgSO4, or MgO; the phosphate buffer solution contains 0.5-1.5% poloxamer and 0.1-1% dopamine; the heating and stirring temperature is 55-65℃; in step S3, the zinc is provided by ZnO or zinc gluconate.

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