A GEL formulation with antibacterial properties for use in the elimination of skin infections and a preparation method thereof based on green chemistry

Abstract

The invention relates to a gel formulation with antibacterial properties for use in the elimination of skin infections and a preparation method thereof based on green chemistry. Since the formulation of the invention is new, there is no resistance developed to the antibacterial activity of the formulation yet. In this way, the formulation of the invention offers an effective treatment in the elimination of skin infections. Thanks to the use of zinc oxide nanoparticles in the gel formulation of the invention, a more effective treatment can be provided in the infection area with the controlled and slow release of the medicament. A green chemistry based preparation method is presented which enables safer, environmentally friendly, economical and controlled production of zinc oxide (ZnO) nanoparticles by using the outer green shell surrounding the outside of the walnut plant in the production of the formulation of the invention.

Description

[0001] A GEL FORMULATION WITH ANTIBACTERIAL PROPERTIES FOR USE IN THE ELIMINATION OF SKIN INFECTIONS AND A PREPARATION METHOD THEREOF BASED ON GREEN CHEMISTRY

[0002] Technical Field of the Invention

[0003] The invention relates to a gel formulation with antibacterial properties for use in the elimination of skin infections and a preparation method thereof based on green chemistry.

[0004] State of the Art

[0005] The skin, epidermis, or flesh is the outermost layer covering the bodies of some animals, and is an organ of the integumentary system consisting of layers of tissue that protect the muscles and organs underneath[1]. If the skin is exposed to a large number of microorganisms, opportunistic pathogens residing in the flora disrupt the integrity of the skin and the aforementioned pathogens make the skin vulnerable to infection. For this reason, skin infections are among the most common infections encountered in society. Topical antibiotics are needed in the treatment of skin infections and the antiinflammatory effects of antibiotics are utilized. Topical antibiotics such as oxytetracycline hydrochloride, fucidic acid, mupirocin, retapamulin and clindamycin are frequently used active ingredients in the treatment of skin infections. However, it has been discovered that there are microorganisms capable of showing resistance these antibiotics and active ingredients with long-term use. Studies conducted show that susceptibility to antibiotics decreases over time.

[0006] In the state of the art, it is very difficult to say that topical antibiotics used in skin infections are effective enough in eliminating skin infections. Although the first reason for this is the emergence of microorganisms showing resistance to these antibiotics as a result of long-term use of topical antibiotics such as oxytetracycline hydrochloride, fucidic acid, mupirocin, retapamulin, and clindamycin in the present art, there are other reasons underlying the inability to provide effective treatment. One of these reasons is that the controlled and slow release of topical antibiotics used in skin infections cannot be provided sufficiently. Controlled release systems ensure that the active substance is released locally or systematically at predetermined rates and specific time intervals. The benefits of controlled medicament release are listed as continuously maintaining medicament levels at therapeutic levels, reducing harmful effects due to targeting, reducing the amount of medicament required, reducing dosage to improve patient compliance with the recommended medicament regimen, and facilitating medicament administration for medicaments with short half-life[2], In particular, it is crucial for antibiotics to reduce the amount of medicament required. Because allergic symptoms such as itching and shedding on the skin, difficulty in breathing, sudden low blood pressure, rapid heartbeat, and loss of consciousness can be observed. Digestive system disorders such as diarrhea, constipation, nausea, vomiting, bloating, indigestion, loss of appetite, and abdominal pain are among the harms of antibiotics [3].

[0007] Walnut is a plant that grows widely around the world. The wet shell formed on the outer surface is called fresh green walnut shell. Its antimicrobial and antioxidant properties, which are quite abundant in the green shell and leaf parts, make this plant special. The green shell and leaf parts of the walnut plant are seen as waste and an effective attempt to recycle these parts is not yet included in the present art. While there are problems such as the use of toxic chemicals in the synthesis phase and the high costs of synthesis containing toxic chemicals, especially in recent years, it has become a necessity to expand the use of plant wastes with antimicrobial and antioxidant properties such as walnuts in order to utilize the wastes and to disseminate the green synthesis procedure. Unconscious consumption of natural resources and economic difficulties have made it necessary to use natural resources for multiple purposes. On the other hand, the resistance of microorganisms to natural and synthetic antibiotics developed for the treatment of diseases that cause infection leaves the treatments unanswered. Due to this resistance, it is of great importance to expand the use of new, natural, and different antibacterial raw material sources such as walnuts, especially in consumer products such as medicaments.

[0008] Due to reasons such as the limitations and inadequacies of topical antibiotics and the synthesis methods thereof to be used in the elimination of skin infections in the state of the art, the formation of microorganisms capable of showing resistance to topical antibiotics used in the treatment of skin infections in the present art and therefore the decrease in susceptibility to these antibiotics over time, the inability to provide sufficiently controlled and slow release of topical antibiotics used in skin infections, and the insufficient environmental friendliness of the preparation methods of topical antibiotic formulations in the present art have made it necessary to present a formulation with antibacterial properties to be used in the elimination of skin infections and a green chemistry based preparation method to be used in obtaining thereof, in which all these problems are eliminated.

[0009] Summary and Objects of the Invention

[0010] In the invention, a gel formulation with antibacterial properties for use in the elimination of skin infections and a preparation method thereof based on green chemistry are described. Since the formulation of the invention is new, there is no resistance developed to the antibacterial activity of the formulation yet. In this way, the formulation of the invention offers an effective treatment in the elimination of skin infections. Thanks to the use of zinc oxide nanoparticles in the gel formulation of the invention, a more effective treatment can be provided in the infection area with the controlled and slow release of the medicament. A green chemistry based preparation method is presented which enables safer, environmentally friendly, economical and controlled production of zinc oxide (ZnO) nanoparticles by using the outer green shell surrounding the outside of the walnut plant in the production of the formulation of the invention.

[0011] An object of the invention is to introduce a gel formulation for use in the elimination of skin infections, which exhibits antibacterial activity and for which resistance to its antibacterial activity has not yet been developed. The formulation of the invention has a content that is not encountered in the state of the art. Since said formulation is new, there is no resistance developed to the antibacterial activity of the formulation yet. In this way, the formulation of the invention offers an effective treatment in the elimination of skin infections. A gel formulation with antibacterial properties of the invention for use in the elimination of skin infections comprises the green shell of the walnut (Juglans regia) plant, clarithromycin, zinc oxide (ZnO) nanoparticles, and gel.

[0012] Another object of the invention is to introduce a gel formulation for use in the elimination of skin infections, exhibiting antibacterial activity and enabling a controlled and slow release of the medicament at the site of infection, thus providing a more effective treatment. Thanks to the use of zinc oxide nanoparticles in the gel formulation of the invention, a more effective treatment can be provided in the infection area with the controlled and slow release of the medicament.

[0013] In the invention, it is ensured that a gel formulation with antibacterial properties is obtained in an environmentally friendly way to be used in the elimination of skin infections. The green shell parts of the walnut plant, which are considered as waste, are recycled while obtaining the formulation of the invention. A green chemistry based preparation method is presented which enables safer, environmentally friendly, economical and controlled production of zinc oxide (ZnO) nanoparticles by using the outer green shell surrounding the outside of the walnut plant in the production of the formulation of the invention. In the green chemistry-based preparation method of a gel formulation with antibacterial properties of the invention for use in the elimination of skin infections, the use of waste shells during the walnut harvesting months every year will be an important step for both the environment and human health and treatment. The beneficial molecule in walnut shells, which will be used in the utilization of wastes and in the treatment of bacterial skin disease, is jugion. Jugion (5-hydroxy-l, 4- naphthalenedione) is an important molecule with naphthaquinone structure.

[0014] With the invention, a gel formulation with antibacterial properties is introduced for use in the elimination of skin infections, which does not cause any harm to the kidneys.

[0015] Description of the Drawings

[0016] Fig. 1. FTIR Spectrum of Zinc oxide Nanoparticles.

[0017] Fig. 2. SEM Image of Zinc Oxide Nanoparticles.

[0018] Fig. 3. XRD Result of Zinc Oxide Nanoparticles.

[0019] Fig. 4. FTIR Spectrum of Clarithromycin-Bound Zinc Oxide Nanoparticles.

[0020] Fig. 5. SEM Image of Clarithromycin-Bound Zinc Oxide Nanoparticles.

[0021] Fig. 6a. Release Graph of Clarithromycin in Free Form (pH 7.4).

[0022] Fig. 6b. Clarithromycin Release Graph from Clarithromycin-Bound Zinc Oxide Nanoparticles (pH 7.4).

[0023] Fig. 6c. Clarithromycin Release Graph from Carbopol Gel Containing Clarithromycin- Bound Zinc Oxide Nanoparticles (pH 7.4).

[0024] Detailed Description of the Invention The invention relates to a gel formulation with antibacterial properties for use in the elimination of skin infections and a preparation method thereof based on green chemistry. Since the formulation of the invention is new, there is no resistance developed to the antibacterial activity of the formulation yet. In this way, the formulation of the invention offers an effective treatment in the elimination of skin infections. Thanks to the use of zinc oxide nanoparticles in the gel formulation of the invention, a more effective treatment can be provided in the infection area with the controlled and slow release of the medicament. A green chemistry based preparation method is presented which enables safer, environmentally friendly, economical and controlled production of zinc oxide (ZnO) nanoparticles by using the outer green shell surrounding the outside of the walnut plant in the production of the formulation of the invention. A gel formulation with antibacterial properties of the invention for use in the elimination of skin infections comprises the green shell of the walnut (Juglans regia) plant, clarithromycin, zinc oxide (ZnO) nanoparticles, and a cross-linked polyacrylic acid polymer gel.

[0025] A gel formulation with antibacterial properties of the invention for use in the elimination of skin infections comprises;

[0026] • green shell of walnut Juglans regia) plant,

[0027] • clarithromycin,

[0028] • zinc oxide (ZnO) nanoparticles,

[0029] • A cross-linked polyacrylic acid polymer gel.

[0030] The cross-linked polyacrylic acid polymer mentioned here is Carbopol 940.

[0031] In an embodiment of the invention, a gel formulation with antibacterial properties of the invention for use in the elimination of skin infections comprises;

[0032] • green shell of walnut (Juglans regia) plant,

[0033] • clarithromycin at a concentration of 130-260 pg drug / g gel,

[0034] • zinc oxide (ZnO) nanoparticles at a concentration of 0.9-2.4 mg nanoparticles / g gel,

[0035] • a polyacrylic acid polymer gel cross-linked at a rate of 0.7-1.6% (w / v). The cross-linked polyacrylic acid polymer gel mentioned here is Carbopol 940.

[0036] In an embodiment of the invention, a gel formulation with antibacterial properties of the invention for use in the elimination of skin infections comprises;

[0037] • green shell of walnut (Juglans regia) plant,

[0038] • clarithromycin at a concentration of 200 pg drug / g gel,

[0039] • zinc oxide (ZnO) nanoparticles at a concentration of 1.6 mg nanoparticles / g gel,

[0040] • a polyacrylic acid polymer gel cross-linked at a rate of 1% (w / v).

[0041] The cross-linked polyacrylic acid polymer gel mentioned here is Carbopol 940.

[0042] A preparation method of a gel formulation with antibacterial properties of the invention for use in the elimination of skin infections comprises the process steps of; i. washing the green shell parts of the walnut (Juglans regia) plant and drying them in a drying oven, then grinding the dried green shells and transferring them into a container, and then adding the ground green shells to boiling water and allowing them to steep, followed by filtering through filter paper, and obtaining the extract from the green shells of the walnut (Juglans regia) plant, ii. taking the obtained extract and adding it dropwise to a zinc nitrate [Zn(NO3)2] salt solution with a pH of 8, then boiling the mixture and centrifuging to separate the supernatant, followed by drying the pellets in a drying oven, and thereby completing the synthesis of zinc oxide (ZnO) nanoparticles using the green synthesis method, iii. mixing clarithromycin with zinc oxide (ZnO) nanoparticles and leaving for incubation in an orbital mixer at room temperature, followed by applying a centrifugation process to separate the supernatant after incubation, washing the obtained pellets with distilled water, and thereby completing the process of binding clarithromycin to zinc oxide (ZnO) nanoparticles, iv. adding a cross-linked polyacrylic acid polymer gel into the clarithromycin-bound zinc oxide nanoparticle dispersion and mixing at room temperature, followed by the dropwise addition of triethanolamine during mixing with a mechanical mixer to adjust and neutralize the solution pH to around 6, and thereby preparing a cross-linked polyacrylic acid polymer gel formulation containing clarithromycin-bound zinc oxide nanoparticles.

[0043] The cross-linked polyacrylic acid polymer gel mentioned in the process step number iv is Carbopol 940. In an embodiment of the invention, a preparation method of a gel formulation with antibacterial properties of the invention for use in the elimination of skin infections comprises the process steps of; i. washing the green shell parts of the walnut (Juglans regia) plant and drying them in a drying oven at 40-65 °C for 40-65 hours, then grinding the dried green shells and transferring them into a container, and then adding 0.2-1 grams of ground green shells to 80-125 mL of boiling water and allowing them to steep for -20-60 minutes, followed by filtering through filter paper, and obtaining the extract from the green shells of the walnut Juglans regia L.)) plant, ii. taking 5-20 mL of the obtained extract and adding it dropwise to 20-80 mL of zinc nitrate [Zn(NO3)2] salt solution of 1 -5 mM with a pH of 8, then boiling the mixture at 50-100 °C for 5-30 minutes and centrifuging at 8,000-13,000 rpm for 10-30 minutes to separate the supernatant, followed by drying the pellets in a drying oven, and thereby completing the synthesis of zinc oxide (ZnO) nanoparticles using the green synthesis method, iii. mixing clarithromycin at a concentration of 620-1200 pg / mL with zinc oxide

[0044] (ZnO) nanoparticles at a ratio of 1 :1 by volume and leaving for incubation in an orbital mixer at room temperature for 16 hours, followed by applying a centrifugation process at 8,000-13,000 rpm for 10-30 minutes to separate the supernatant after incubation, washing the obtained pellets twice with distilled water, and thereby completing the process of binding clarithromycin to zinc oxide (ZnO) nanoparticles, iv. adding 2 mL of clarithromycin-bound zinc oxide nanoparticle dispersion into 5-

[0045] 20 grams of a cross-linked polyacrylic acid polymer gel and mixing at room temperature for 15-35 hours, followed by the dropwise addition of 50-150 pL of triethanolamine during mixing with a mechanical mixer to adjust and neutralize the solution pH to around 6, and thereby preparing a cross-linked polyacrylic acid polymer gel formulation containing clarithromycin-bound zinc oxide nanoparticles.

[0046] The cross-linked polyacrylic acid polymer gel mentioned in the process step number iv is Carbopol 940.

[0047] In an embodiment of the invention, a preparation method of a gel formulation with antibacterial properties of the invention for use in the elimination of skin infections comprises the process steps of; i. washing the green shell parts of the walnut (Juglans regia) plant and drying them in a drying oven at 50 °C for 48 hours, then grinding the dried green shells and transferring them into a container, and then adding 0.5 grams of ground green shells to 100 mL of boiling water and allowing them to steep for 30 minutes, followed by filtering through filter paper, and obtaining the extract from the green shells of the walnut Juglans regia L.)) plant, ii. taking 10 mL of the obtained extract and adding it dropwise to 40 mL of zinc nitrate [Zn(NO3)2] salt solution of 1 mM with a pH of 8, then boiling the mixture at 80 °C for 15 minutes and centrifuging at 12,000 rpm for 20 minutes to separate the supernatant, followed by drying the pellets in a drying oven, and thereby completing the synthesis of zinc oxide (ZnO) nanoparticles using the green synthesis method, iii. mixing clarithromycin at a concentration of 800 pg / mL with zinc oxide (ZnO) nanoparticles at a ratio of 1 :1 by volume and leaving for incubation in an orbital mixer at room temperature for 16 hours, followed by applying a centrifugation process at 12,000 rpm for 20 minutes to separate the supernatant after incubation, washing the obtained pellets twice with distilled water, and thereby completing the process of binding clarithromycin to zinc oxide (ZnO) nanoparticles, iv. adding 2 mL of clarithromycin-bound zinc oxide nanoparticle dispersion into 10 grams of a cross-linked polyacrylic acid polymer gel and mixing at room temperature for 24 hours, followed by the dropwise addition of 100 pL of triethanolamine during mixing with a mechanical mixer to adjust and neutralize the solution pH to around 6, and thereby preparing a cross-linked polyacrylic acid polymer gel formulation containing clarithromycin-bound zinc oxide nanoparticles.

[0048] The cross-linked polyacrylic acid polymer gel mentioned in the process step number iv is Carbopol 940.

[0049] In the preparation method of a gel formulation with antibacterial properties of the invention for use in the elimination of skin infections, the characterization of zinc oxide (ZnO) nanoparticles obtained after the application of process steps i and ii, respectively, was carried out, and the chemical bonds of the obtained nanoparticles were determined by FTIR analysis, the size and morphology of the synthesized nanoparticles were determined by SEM analysis and information about the atomic arrangement of the substance was determined by XRD analysis. Distinct zinc oxide specific peaks (603-1595cm1vibrations and 1378-1394cm1vibrations) were observed in the FTIR spectrum and are shown in Fig. 1. Spherical shaped nanoparticles with an average size of 22 nm were observed by SEM analysis as shown in Fig. 2. The XRD image shows the main peak points corresponding to the 20 values of 31.93°, 34.62° and 36.44°, 47.76°, 56.79°, 62.98°, 63.19°, 66.59°, 68.00°, 68.29° (Fig. 3). Clarithromycin is bound to the zinc oxide (ZnO) nanoparticle in the process step number iii in the preparation method of a gel formulation with antibacterial properties of the invention for the elimination of skin infections. Medicament quantities were calculated by absorbance measurement at UV-Vis spectrophotometer 272 nm. In nanoparticles prepared at an initial medicament concentration of 800 pg / mL, a 74% medicament binding efficiency was achieved, and this initial concentration was selected as the optimum. The FTIR spectrum for the characterization of clarithromycin- bound zinc oxide nanoparticles is shown in Fig. 4 and the SEM images are shown in Fig. 5. In SEM images, it was observed that there was an increase in the structure of clarithromycin-bound zinc oxide nanoparticles with an average size of 43 nm compared to the zinc oxide nanoparticle size, and there was an increase in size due to the binding medicament molecules. The release of the medicament in its free form in a pH 7.4 PBS buffer medium (Fig. 6.a), its release from the zinc oxide nanoparticle dispersion (Fig. 6.b), and its release from the gel containing the zinc oxide nanoparticle dispersion (Fig. 6.c) were examined for 24-hours. The slowest release was observed in the gel form, while the fastest release was found in the free medicament form. References

[0050] [1] Wikimedia Foundation. (n.d.). Deri. Wikipedia. https: / / tr.wikipedia.org / wiki / Deri#:~:text=Deri%2C%20cilt%20veya%20ten%2C%20baz %C4%B1 ,olu%C5%9Fan%20bir%20%C3%B6rt%C3%BC%20sistemi%20organ%C4% B1d%C4%B1 r.

[0051] [2] Kontrollu Haq Salinimi. PPT. (n.d.). https: / / www.slideshare.net / EczaciLaleHn / kontroll-ila-salnm

[0052] [3] Antibiyotik Nedir? Nasil Kullanilmalidir? Yan Etkileri Nelerdir?. Medical Park. (n.d.). https: / / www.medicalpark.com.tr / antibiyotik-nedir-nasil-kullanilmalidir-yan-etkileri- nelerdir / hg-

[0053] 1846#:~:text=Deride%20ka%C5%9F%C4%B1 nt%C4%B1 %20ve%20d%C3%B6k%C3 %BCImeler%2C%20nefes,antibiyotik%20zararlar%C4%B1 %20aras%C47oB1 nda%20y er%20al%C4%B1 r.

Claims

CLAIMS1. A gel formulation with antibacterial properties for use in the elimination of skin infections, characterized in that it comprises;• green shell of walnut (Juglans regia) plant,• clarithromycin,• zinc oxide (ZnO) nanoparticles,• A cross-linked polyacrylic acid polymer gel.

2. A gel formulation according to claim 1 , characterized in that it comprises;• green shell of walnut (Juglans regia) plant,• clarithromycin at a concentration of 130-260 pg drug / g gel,• zinc oxide (ZnO) nanoparticles at a concentration of 0.9-2.4 mg nanoparticles / g gel,• a polyacrylic acid polymer gel cross-linked at a rate of 0.7-1.6% (w / v).

3. A gel formulation according to claim 2, characterized in that it comprises;• green shell of walnut (Juglans regia) plant,• clarithromycin at a concentration of 200 pg drug / g gel,• zinc oxide (ZnO) nanoparticles at a concentration of 1.6 mg nanoparticles / g gel,• a polyacrylic acid polymer gel cross-linked at a rate of 1% (w / v).

4. A gel formulation according to any one of the claims 1 -3, characterized in that the cross-linked polyacrylic acid polymer gel mentioned is Carbopol 940.

5. A preparation method of a gel formulation with antibacterial properties for use in the elimination of skin infections, characterized in that it comprises the process steps of; i. washing the green shell parts of the walnut (Juglans regia) plant and drying them in a drying oven, then grinding the dried green shells and transferring them into a container, and then adding the ground green shells to boiling water and allowing them to steep, followed by filtering through filter paper,and obtaining the extract from the green shells of the walnut (Juglans regia) plant, ii. taking the obtained extract and adding it dropwise to a zinc nitrate [Zn(NO3)2] salt solution with a pH of 8, then boiling the mixture and centrifuging to separate the supernatant, followed by drying the pellets in a drying oven, and thereby completing the synthesis of zinc oxide (ZnO) nanoparticles using the green synthesis method, iii. mixing clarithromycin with zinc oxide (ZnO) nanoparticles and leaving for incubation in an orbital mixer at room temperature, followed by applying a centrifugation process to separate the supernatant after incubation, washing the obtained pellets with distilled water, and thereby completing the process of binding clarithromycin to zinc oxide (ZnO) nanoparticles, iv. adding a cross-linked polyacrylic acid polymer gel into the clarithromycin- bound zinc oxide nanoparticle dispersion and mixing at room temperature, followed by the dropwise addition of triethanolamine during mixing with a mechanical mixer to adjust and neutralize the solution pH to around 6, and thereby preparing a cross-linked polyacrylic acid polymer gel formulation containing clarithromycin-bound zinc oxide nanoparticles.

6. A preparation method according to claim 5, characterized in that it comprises the process steps of; i. washing the green shell parts of the walnut Juglans regia) plant and drying them in a drying oven at 40-65 °C for 40-65 hours, then grinding the dried green shells and transferring them into a container, and then adding 0.2-1 grams of ground green shells to 80-125 mL of boiling water and allowing them to steep for -20-60 minutes, followed by filtering through filter paper, and obtaining the extract from the green shells of the walnut (Juglans regia L.)) plant, ii. taking 5-20 mL of the obtained extract and adding it dropwise to 20-80 mL of zinc nitrate [Zn(NO3)2] salt solution of 1 -5 mM with a pH of 8, then boiling the mixture at 50-100 °C for 5-30 minutes and centrifuging at 8,000- 13,000 rpm for 10-30 minutes to separate the supernatant, followed by drying the pellets in a drying oven, and thereby completing the synthesis of zinc oxide (ZnO) nanoparticles using the green synthesis method,iii. mixing clarithromycin at a concentration of 620-1200 pg / mL with zinc oxide (ZnO) nanoparticles at a ratio of 1 :1 by volume and leaving for incubation in an orbital mixer at room temperature for 16 hours, followed by applying a centrifugation process at 8,000-13,000 rpm for 10-30 minutes to separate the supernatant after incubation, washing the obtained pellets twice with distilled water, and thereby completing the process of binding clarithromycin to zinc oxide (ZnO) nanoparticles, iv. adding 2 mL of clarithromycin-bound zinc oxide nanoparticle dispersion into 5-20 grams of a cross-linked polyacrylic acid polymer gel and mixing at room temperature for 15-35 hours, followed by the dropwise addition of 50-150 pL of triethanolamine during mixing with a mechanical mixer to adjust and neutralize the solution pH to around 6, and thereby preparing a cross-linked polyacrylic acid polymer gel formulation containing clarithromycin-bound zinc oxide nanoparticles.

7. A preparation method according to claim 6, characterized in that it comprises the process steps of; i. washing the green shell parts of the walnut (Juglans regia) plant and drying them in a drying oven at 50 °C for 48 hours, then grinding the dried green shells and transferring them into a container, and then adding 0.5 grams of ground green shells to 100 mL of boiling water and allowing them to steep for 30 minutes, followed by filtering through filter paper, and obtaining the extract from the green shells of the walnut Juglans regia L.)) plant, ii. taking 10 mL of the obtained extract and adding it dropwise to 40 mL of zinc nitrate [Zn(NO3)2] salt solution of 1 mM with a pH of 8, then boiling the mixture at 80 °C for 15 minutes and centrifuging at 12,000 rpm for 20 minutes to separate the supernatant, followed by drying the pellets in a drying oven, and thereby completing the synthesis of zinc oxide (ZnO) nanoparticles using the green synthesis method, iii. mixing clarithromycin at a concentration of 800 pg / mL with zinc oxide (ZnO) nanoparticles at a ratio of 1 :1 by volume and leaving for incubation in an orbital mixer at room temperature for 16 hours, followed by applying a centrifugation process at 12,000 rpm for 20 minutes to separate thesupernatant after incubation, washing the obtained pellets twice with distilled water, and thereby completing the process of binding clarithromycin to zinc oxide (ZnO) nanoparticles, iv. adding 2 mL of clarithromycin-bound zinc oxide nanoparticle dispersion into 10 grams of a cross-linked polyacrylic acid polymer gel and mixing at room temperature for 24 hours, followed by the dropwise addition of 100 pL of triethanolamine during mixing with a mechanical mixer to adjust and neutralize the solution pH to around 6, and thereby preparing a cross-linked polyacrylic acid polymer gel formulation containing clarithromycin-bound zinc oxide nanoparticles.

8. A preparation method according to any one of the claims 5-7, characterized in that the cross-linked polyacrylic acid polymer gel mentioned in the process number iv is Carbopol 940.

9. A gel formulation with antibacterial properties for use in the elimination of skin infections prepared by a method according to any one of the claims 5-8.

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