A composition for preventing or treating periodontal disease and a dental composite antibiotic ointment composition

Abstract

The present invention relates to a composition for preventing or treating periodontal disease and a dental composite antibiotic ointment composition. The composition for preventing or treating periodontal disease according to the present invention comprises minocycline and metronidazole as effective ingredients.

Description

Technical Field

[0001] This invention relates to a composition for the prevention or treatment of periodontal disease and a dental compound antibiotic ointment composition. Background Technology

[0002] Periodontal disease is caused by bacterial infection resulting from poor oral hygiene in the gums, teeth, and implant sites. It mainly includes periodontitis occurring in natural teeth and peri-implantitis occurring at the implantation site of dental implants. In cases of periodontitis, as it progresses to a severe stage, symptoms include increased periodontal pocket depth, bleeding, gingival recession, and bone loss.

[0003] Peri-implantitis is similar to periodontitis, but unlike periodontitis, the lesions extend to the area around the root tip and manifest as acute inflammatory symptoms. Furthermore, the oral microbiome distribution in periodontitis differs from that in periodontitis, leading to peri-implant redness, edema, mucosal hyperplasia, abscesses, bleeding, increased periodontal pocket depth, and accelerated bone loss.

[0004] Although the symptoms of periodontitis and peri-implantitis differ, treatment methods can be divided into surgical and non-surgical approaches, and similar treatments can be applied to each condition. Surgically, in the case of periodontitis, procedures such as gingival incision to remove tartar and root planing are performed to remove inflammation, tartar, and plaque, as well as to reshape the gingiva. In the case of peri-implantitis, inflammation is removed in a similar manner to periodontitis, sometimes involving the use of lasers or nickel-titanium brushes to remove the biofilm on the implant surface. If necessary, bone grafting can be performed in both periodontal diseases to repair lost alveolar bone.

[0005] For non-surgical treatment, both periodontitis and peri-implantitis are treated with antibiotics. Existing dental antibiotic ointments use minocycline hydrochloride as the main ingredient for non-surgical treatment. With dental ointments, after removing tartar, plaque, and inflammation from the periodontal pockets, the ointment is injected into the pockets to directly administer antibiotics, thus providing local treatment. Currently available dental ointments have numerous clinical cases demonstrating their effectiveness against periodontitis.

[0006] However, for the treatment of peri-implantitis, existing single-component dental ointments are insufficient to address all the oral microorganisms associated with this symptom, and due to pathological differences, existing treatments have limitations as a definitive non-surgical treatment for peri-implantitis. Therefore, it is necessary to explore the use of other medications.

[0007] Therefore, in order to solve the problems of existing single-component dental ointments, this invention develops an antibiotic ointment composition that combines two antibiotics. This invention provides a non-surgical treatment agent for periodontal diseases such as periodontitis and peri-implantitis, which is more effective in treating these conditions than existing single-component dental ointments.

[0008] Patent Document 1: Persson GR, Renvert S. Cluster of bacteria associated with peri-implantitis. Clin Implant Dent Relat Res. 2014 Dec;16(6):783-93. doi:10.1111 / cid.12052. Epub 2013 Mar 25. PMID: 23527870; Patent Document 2: Maruyama, N., Maruyama, F., Takeuchi, Y. et al. Intrain individual variation in core microbiota in peri-implantitis and periodontitis. Sci Rep 4, 6602 (2014); Patent Document 3: Heitz-Mayfield LJ, Lang NP. Surgical and nonsurgicalperiodontal therapy. Learned and unlearned concepts. Periodontol 2000. 2013Jun;62(1):218-31. doi: 10.1111 / prd.12008. PMID: 23574468; Patent document 4: Korean Patent Registration No. 10-0252699; Patent Document 5: Berglundh T, Zitzmann NU, Donati M. Are peri-implantitis lesions different from periodontitis lesions? J Clin Periodontol. 2011 Mar;38Suppl 11:188-202. doi: 10.1111 / j.1600-051X.2010.01672.x. PMID: 21323715; Patent document 6: Becker ST, Beck-Broichsitter BE, Graetz C, Dφrfer CE, Wiltfang J, Hasler R. Peri-implantitis versus periodontitis: functional differences indicated by transcriptome profiling. Clin Implant Dent RelatRes. 2014 Jun;16(3):401-11. doi: 10.1111 / cid.12001. Epub 2012 Sep 11. PMID: 22967131. Summary of the Invention

[0009] The problem that the invention aims to solve In order to solve the problems of the prior art, the inventors provide a composition for the prevention or treatment of periodontal disease, which contains minocycline and metronidazole as active ingredients.

[0010] means for solving problems To address the aforementioned problems, the present invention provides a composition for the prevention or treatment of periodontal disease, wherein the composition comprises minocycline and metronidazole as active ingredients.

[0011] In addition, this composition can provide a composition for the prevention or treatment of periodontal disease, wherein the minocycline comprises minocycline hydrochloride as an active ingredient, and the metronidazole comprises metronidazole benzoate as an active ingredient.

[0012] Additionally, this composition can provide a composition for the prevention or treatment of periodontal disease, wherein the minocycline and the metronidazole are mixed in a weight ratio of 1:1 to 1:25.

[0013] Additionally, this composition can provide a composition for the prevention or treatment of periodontal disease, wherein the metronidazole has a particle size (D90) of 5 to 150 μm.

[0014] Additionally, this composition provides a composition for the prevention or treatment of periodontal disease, wherein the metronidazole has a bulk density of 0.2 to 0.5 g / cm³. 3 .

[0015] In another embodiment of the present invention, a dental compound antibiotic ointment composition is provided, wherein the dental compound antibiotic ointment composition comprises minocycline, metronidazole, a matrix, an emulsifier, a viscosity modifier, a stabilizer, and an antioxidant.

[0016] In addition, this ointment can provide a dental compound antibiotic ointment composition, wherein the minocycline is used at a ratio of 0.1 to 2% by weight of the total weight of the ointment, and the metronidazole is used at a ratio of 0.1 to 50% by weight of the total weight of the ointment.

[0017] In addition, this ointment provides a dental compound antibiotic ointment composition, wherein the base is used at a ratio of 5 to 25% by weight of the total weight of the ointment, and the base comprises any one or more selected from the group consisting of concentrated glycerin, polyethylene glycol 400, polyethylene glycol 4000, propylene glycol, 1,3-propanediol, isopentyl glycol, pentylene glycol, hexanediol, butylene glycol, diethylene glycol, dipropylene glycol, diglycerol, erythritol, arabinitol, arabinitol, sorbitol, mannitol, xylitol, galactitol, glucose, fructose, xylose, trehalose, maltose, sucrose, and lactose.

[0018] In addition, this ointment provides a dental compound antibiotic ointment composition, wherein the emulsifier is used at a ratio of 20 to 50% by weight of the total weight of the ointment, and the emulsifier comprises any one or more selected from the group consisting of glyceryl monostearate, glyceryl monooleate, glyceryl monolaurate, glyceryl monopalmitate, acetylated glyceryl monostearate, white petrolatum, liquid paraffin, paraffin, stearic acid, cetearyl alcohol, isopropyl myristate, and cetyl palmitate.

[0019] In addition, this ointment provides a dental compound antibiotic ointment composition, wherein the viscosity modifier is used at a ratio of 1 to 20% by weight of the total weight of the ointment, and the viscosity modifier comprises any one or more of the following: mineral oil, sesame oil, tea tree oil, avocado oil, castor oil, rapeseed oil, coffee oil, corn oil, jojoba oil, kaya oil, flaxseed oil, macadamia oil, olive oil, peanut oil, rapeseed oil, cottonseed oil, rice bran oil, safflower seed oil, camellia oil, sunflower seed oil, soybean oil, shea butter, green tea seed oil, borage oil, walnut oil, evening primrose oil, lanolin oil, calendula oil, rosehip oil, coconut oil, mustard oil, palm oil, palm kernel oil, apricot kernel oil, grape seed oil, castor oil, poppy seed oil, argan oil, flaxseed oil, almond oil, hazelnut oil, hemp seed oil, and pumpkin seed oil.

[0020] In addition, this ointment can provide a dental compound antibiotic ointment composition, wherein the stabilizer is used in a proportion of 1 to 8% by weight of the total weight of the ointment, and the stabilizer comprises magnesium chloride.

[0021] In addition, this ointment can provide a dental compound antibiotic ointment composition, wherein the antioxidant is used at a proportion of less than 2% by weight of the total weight of the ointment, and the antioxidant comprises ascorbyl palmitate.

[0022] Invention Effects The composition for the prevention or treatment of periodontal disease according to the present invention has the effect of treating these diseases by applying a compound antibiotic to remove bacteria caused by periodontal diseases such as peri-implantitis or periodontitis that cannot be resolved by single-component antibiotics. Attached Figure Description

[0023] The following drawings accompanying this specification are used to illustrate preferred embodiments of the invention and, together with the detailed description of the invention, are used to further understand the technical concept of the invention. Therefore, the invention should not be construed as being limited to the contents described in these drawings.

[0024] Figure 1 This is a graph showing the results of a syringe injection force test on a dental compound antibiotic ointment composition according to an embodiment of the present invention.

[0025] Figure 2 and Figure 3 This is a graph showing the results of tests conducted on the injection force of a syringe according to a comparative example of the present invention.

[0026] Figure 4 This is a graph showing the results of a test on the adhesion of a dental compound antibiotic ointment composition and a single-component ointment, namely Comparative Example 1, to artificial saliva according to an embodiment of the present invention.

[0027] Figure 5 This is a graph showing the viscosity and properties of an ointment composition based on the bulk density of metronidazole benzoate according to an embodiment of the present invention.

[0028] Figure 6 This is a graph showing the results of measuring the periodontal pocket depth restoration rate after treating an ointment composition according to an embodiment of the present invention and a single-component ointment, namely Comparative Example 1.

[0029] Figure 7 This is a graph showing the presence or absence of inflammatory changes after treatment with an ointment composition according to an embodiment of the present invention and a single-component ointment, i.e., Comparative Example 1.

[0030] Best practice To address the aforementioned problems, the present invention provides a composition for the prevention or treatment of periodontal disease, wherein the composition for the prevention or treatment of periodontal disease comprises minocycline and metronidazole as active ingredients. Detailed Implementation

[0031] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. These embodiments are illustrated to fully convey the spirit of the invention to those skilled in the art. The present invention is not limited to the embodiments illustrated herein, and may be embodied in other ways. In the drawings, figures of parts irrelevant to the description may be omitted to make the invention clearer, and the dimensions of the constituent elements may be exaggerated for ease of understanding.

[0032] The technical terms used in this specification are for illustrative purposes only and are not intended to limit the invention. Furthermore, unless the context clearly indicates otherwise, the singular forms used herein include the plural forms. Additionally, the terms "comprising" or "containing" as used herein are used to embody specific characteristics, regions, integers, steps, actions, elements, or components, and do not exclude the addition of other specific characteristics, regions, integers, steps, actions, elements, or components.

[0033] In this invention, terms such as "first" and "second" are used to describe various constituent elements, and these terms are only used for the purpose of distinguishing one constituent element from other constituent elements.

[0034] Furthermore, the terminology used in this specification is for illustrative purposes only and is not intended to limit the invention. Unless explicitly indicated in the context, singular expressions include plural expressions. It should be understood that in this specification, terms such as "comprising," "possessing," or "having" are used to indicate the presence of implemented features, values, steps, constituent elements, or combinations thereof, and do not preclude the possibility of the presence or addition of one or more other features, values, steps, constituent elements, or combinations thereof.

[0035] This invention can be modified in various ways and can have multiple implementations. Specific embodiments are shown below with detailed descriptions. However, this is not intended to limit the invention to the specific embodiments disclosed, but should be understood to include all modifications, equivalents, and substitutions that fall within the scope of the ideas and techniques of this invention.

[0036] The following describes in detail the compositions for the prevention or treatment of periodontal disease and the dental compound antibiotic ointment compositions according to the present invention.

[0037] The composition for the prevention or treatment of periodontal disease according to an embodiment of the present invention comprises minocycline and metronidazole as active ingredients.

[0038] Minocycline and metronidazole are antibiotics that can be used to prevent or treat periodontal disease. By using the widely available minocycline in combination with metronidazole, bacteria that cannot be treated by single-component antibiotics can be effectively managed.

[0039] For example, the minocycline may contain minocycline hydrochloride as an active ingredient, and the metronidazole may contain metronidazole benzoate as an active ingredient.

[0040] The minocycline and the metronidazole can be mixed in a weight ratio of 1:1 to 1:25 for use.

[0041] When the mixing ratio of minocycline to metronidazole is less than 1:1, the drug concentration is too low to produce a therapeutic effect; when it is greater than 1:25, there are problems in maintaining the properties of the ointment formulation.

[0042] The particle size (D90) of the metronidazole can be from 5 to 150 μm.

[0043] When the particle size of the metronidazole is less than 5 μm, the viscosity of the composition becomes too high, the dispersibility within the composition is poor, it is easy to clump, and it is difficult to obtain the effect of the metronidazole. When the particle size is greater than 150 μm, the viscosity of the composition decreases, and when using a syringe nozzle (nozzle diameter 0.4~0.6 mm) that can be applied to periodontal pockets, there is a problem of clogging.

[0044] Preferably, the particle size (D90) of the metronidazole can be 5 to 100 μm, the particle size (D90) of the metronidazole can be 10 to 90 μm, or the particle size (D90) of the metronidazole can be 20 to 50 μm.

[0045] The density of the metronidazole can be from 0.2 to 0.5 g / cm³. 3 .

[0046] When the density of the metronidazole is less than 0.2 g / cm³ 3 When the viscosity of the composition or ointment is too high, its spreadability decreases when used as an ointment; when the density of the metronidazole is greater than 0.5 g / cm³... 3 When used as an ointment, its viscosity is too low, making it difficult to apply and causing it to fall off the skin.

[0047] The composition of the present invention for the prevention or treatment of periodontal disease can be formulated into an ointment.

[0048] The dental compound antibiotic ointment composition according to one embodiment of the present invention comprises minocycline, metronidazole, a matrix, an emulsifier, a viscosity modifier, a stabilizer, and an antioxidant.

[0049] The minocycline can be used at a ratio of 0.1 to 2% by weight of the total weight of the ointment, and the metronidazole can be used at a ratio of 0.1 to 50% by weight of the total weight of the ointment. In order to demonstrate an effective effect for the prevention or treatment of periodontal disease, it is preferred to add it at an effective content.

[0050] The compositions of the present invention for the prevention or treatment of periodontal disease may use a matrix to allow for formulation into an ointment form.

[0051] The matrix may be used at a ratio of 5 to 25% by weight of the total weight of the ointment, and comprises any one or more of the following: concentrated glycerin, polyethylene glycol 400, polyethylene glycol 4000, propylene glycol, 1,3-propanediol, isopentyl glycol, pentylene glycol, hexanediol, butylene glycol, diethylene glycol, dipropylene glycol, diglycerol, erythritol, arabinitol, arabinitol, sorbitol, mannitol, xylitol, galactitol, glucose, fructose, xylose, trehalose, maltose, sucrose, and lactose.

[0052] The emulsifier may be used at a ratio of 20 to 50% by weight of the total weight of the ointment, and comprises any one or more of the group consisting of glyceryl monostearate, glyceryl monooleate, glyceryl monolaurate, glyceryl monopalmitate, acetylated glyceryl monostearate, white petrolatum, liquid paraffin, paraffin, stearic acid, cetearyl alcohol, isopropyl myristate, and cetyl palmitate.

[0053] For example, the matrix and the emulsifier can be mixed in a weight ratio of 1:1 to 1:4 for use.

[0054] When the weight ratio of the matrix to the emulsifier is less than 1:1, the viscosity of the dental compound antibiotic ointment composition is too high, resulting in the problem that it cannot be squeezed out of the syringe; when the weight ratio of the matrix to the emulsifier is greater than 1:4, the viscosity is too low, resulting in the problem that it is difficult to apply as an ointment, cannot adhere to the skin, and falls off.

[0055] The viscosity modifier may be used at a ratio of 1 to 20% by weight of the total weight of the ointment, and comprises any one or more of the following: mineral oil, sesame oil, tea tree oil, avocado oil, castor oil, rapeseed oil, coffee oil, corn oil, jojoba oil, kaya oil, flaxseed oil, macadamia oil, olive oil, peanut oil, rapeseed oil, cottonseed oil, rice bran oil, safflower seed oil, camellia oil, sunflower seed oil, soybean oil, shea butter, green tea seed oil, borage oil, walnut oil, evening primrose oil, lanolin oil, calendula oil, rosehip oil, coconut oil, mustard oil, palm oil, palm kernel oil, apricot kernel oil, grapeseed oil, castor oil, poppy seed oil, argan oil, flaxseed oil, almond oil, hazelnut oil, hemp seed oil, and pumpkin seed oil.

[0056] The stabilizer may be used at a ratio of 1 to 8% by weight of the total weight of the ointment and may contain magnesium chloride.

[0057] The antioxidant may be used at a rate of less than 2% by weight of the total weight of the ointment and may contain ascorbyl palmitate.

[0058] The composition is preferably a pharmaceutical composition, and more preferably a composition in the form of an ointment.

[0059] The composition may be provided as a pharmaceutical composition, comprising only the active ingredient or containing one or more pharmaceutically acceptable carriers, excipients or diluents.

[0060] The term "pharmaceutically acceptable" means that the composition exhibits non-toxic properties to cells or humans exposed to it.

[0061] Furthermore, the composition can be provided by mixing with known substances for treating periodontal disease. That is, the composition can be administered in combination with known compounds that have preventive or therapeutic effects on periodontal disease.

[0062] The term "administration" refers to the introduction of a predetermined substance into an individual through appropriate methods. "Individual" refers to all animals, including humans, rats, mice, and livestock, that have or may develop periodontal disease. As a specific example, it can include mammals, including humans.

[0063] The preferred dosage of the composition varies depending on the patient's condition and weight, disease severity, drug form, route of administration, and duration of administration, but can be appropriately selected by those skilled in the art. However, for optimal effect, the composition is administered at a dose of 0.01 to 1000 mg / kg / day, preferably 0.1 to 500 mg / kg / day, but not limited thereto. The administration can be once daily or divided into multiple doses. The dosage is not limited in any way.

[0064] The present invention will now be described in more detail through examples and experimental cases.

[0065] However, the following embodiments and experimental examples are only for illustrating the present invention, and the content of the present invention is not limited to the following embodiments and experimental examples.

[0066] Example 1 A dental compound antibiotic ointment composition was prepared according to the composition ratios in Table 1 below.

[0067] [Table 1]

[0068] After each ointment was added to a syringe containing the dental compound antibiotic ointment composition prepared according to Example 1, the injection force was measured. As a comparative example, the injection forces of commercially available single-component minocycline products from Company A (Comparative Example 1) and Company B (Comparative Example 2) were compared and measured.

[0069] Here, the composition of Comparative Example 1 includes minocycline hydrochloride as the main component, sodium alginate, plastic base, hydroxypropyl methylcellulose 2910 and polysorbate 80 as the matrix, chitosan as an antioxidant, and sodium carboxymethyl cellulose and carbomer as thickeners; the composition of Comparative Example 2 includes minocycline hydrochloride as the main component, hydroxyethyl cellulose and aminomethyl acrylate copolymer as a sustained-release agent, triacetin as a solubilizer, magnesium chloride as a stabilizer, and concentrated glycerol as a solvent.

[0070] One ml of the dental compound antibiotic ointment composition prepared according to Example 1, Comparative Example 1, and Comparative Example 2 was filled into the plastic syringe container of each syringe. The syringe was mounted on the test stand of a small benchtop precision universal testing machine, and a downward vertical force was applied to the syringe plunger at a speed of 100 ± 5 mm / min using a force gauge. The force required to extrude the ointment from the syringe was measured, and the testing machine was stopped when the volume of ointment in the syringe reached less than 10% of the nominal volume. The maximum load was recorded, and it was confirmed whether the ointment was easily extruded from the syringe container. A load value of 20 N or less was considered acceptable (○), 20 N to 25 N was considered appropriate (Δ), and greater than 25 N was considered unacceptable (×). The results are shown in Table 2 below. Figures 1 to 3 .

[0071] Figure 1 This is a graph showing the results of a syringe injection force test on a dental compound antibiotic ointment composition according to an embodiment of the present invention. Figure 2 and Figure 3 This is a graph showing the results of tests conducted on the injection force of a syringe according to a comparative example of the present invention.

[0072] [Table 2]

[0073] Three artificial saliva adhesion tests were conducted on the dental compound antibiotic ointment composition prepared according to Example 1 and Comparative Example 2 as a comparative example. The results are shown in Table 3 below. Figure 4 . Figure 4 This is a graph showing the results of a test on the adhesion of a dental compound antibiotic ointment composition and a single-component ointment, namely Comparative Example 2, to artificial saliva according to an embodiment of the present invention.

[0074] [Table 3]

[0075] Examples 2 to 4, Comparative Examples 1 to 4 In Example 1, a dental compound antibiotic ointment composition was prepared by adjusting the mixing ratio of concentrated glycerol and glyceryl monooleate corresponding to the matrix and emulsifier as shown in Table 4 below.

[0076] [Table 4]

[0077] In addition, the viscosity of the dental compound antibiotic ointment compositions prepared according to Examples 1 to 3 and Comparative Examples 3 to 6 was measured, and the injection force was measured after each ointment was added to a syringe. The results are shown in Table 5 below.

[0078] [Table 5]

[0079] Examples 4 to 6, Comparative Example 7 and Comparative Example 8 In Example 1, the bulk density of metronidazole benzoate was adjusted as shown in Table 6 below to prepare a dental compound antibiotic ointment composition, and its viscosity was measured. The results are shown in Table 6. Figure 5 .

[0080] Figure 5 This is a graph showing the viscosity and properties of an ointment composition based on the bulk density of metronidazole benzoate according to an embodiment of the present invention.

[0081] [Table 6]

[0082] In addition, the periodontal pocket depth restoration rate after treatment with the dental compound antibiotic ointment compositions prepared according to Example 5 and Comparative Example 8 was tested, and the results are shown below. Figure 6 .

[0083] Figure 6 This is a graph showing the results of measuring the periodontal pocket depth restoration rate after treating an ointment composition according to an embodiment of the present invention and a single-component ointment, namely Comparative Example 1.

[0084] Refer to Table 6 and Figure 6 As shown in blue in the graph corresponding to the packing density of 0.35 in Example 5, it can be seen that the intraperitoneal deep restoration rate increases sharply over time, showing a restoration rate of about 78.90% after three weeks and a high restoration rate of 83.9% after twelve weeks.

[0085] In contrast, in the case of Comparative Example 8 with a packing density of 0.68, as shown in gray in the graph, it can be seen that after twelve weeks, a restoration rate of 68.9% was observed, but this showed a significantly lower periodontal pocket depth restoration rate compared to Example 5.

[0086] Furthermore, in Comparative Example 1, which was used as a single minocycline preparation, as shown in orange in the graph, although the periodontal pocket depth restoration rate was better than that of the untreated ointment (shown in yellow), it was worse than that of the compound antibiotic ointment, especially showing a significantly lower restoration rate compared to Example 5.

[0087] In addition, inflammatory changes were observed after treatment with the dental compound antibiotic ointment compositions prepared according to Example 5 and Comparative Example 8, and the results are presented in... Figure 7 .

[0088] Figure 7 This is a graph showing the presence or absence of inflammatory changes after treatment with an ointment composition according to an embodiment of the present invention and a single-component ointment, i.e., Comparative Example 1.

[0089] Refer to Table 6 and Figure 7 It can be confirmed that: in the case of a bulk density of 0.35 corresponding to Example 5, most of the inflammation disappeared around the second to third week; in the case of a bulk density of 0.68 corresponding to Comparative Example 6, the inflammation disappeared after the fourth week; in the case of Comparative Example 1, which was used as a single agent of minocycline, the inflammation disappeared after the eighth week; and in the case of the untreated group, the inflammation persisted.

[0090] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will understand that it can be easily modified into other specific forms without departing from the technical concept or essential features of the invention. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive. For example, the constituent elements described in a single form may be implemented distributedly, and similarly, the constituent elements described in a distributed manner may be implemented in combination.

[0091] The scope of this invention is defined by the appended claims, but not by the specific embodiments described above. It should be interpreted that all changes or modifications derived from the meaning and scope of the claims and their equivalents are included within the scope of this invention.

Claims

1. A composition for the prevention or treatment of periodontal disease, wherein, The composition for the prevention or treatment of periodontal disease contains minocycline and metronidazole as active ingredients.

2. The composition for preventing or treating periodontal disease according to claim 1, wherein, The minocycline contains minocycline hydrochloride as the active ingredient, and the metronidazole contains metronidazole benzoate as the active ingredient.

3. The composition for preventing or treating periodontal disease according to claim 1, wherein, The minocycline and the metronidazole are mixed in a weight ratio of 1:1 to 1:25 and used.

4. The composition for preventing or treating periodontal disease according to claim 1, wherein, The particle size (D90) of the metronidazole is 5 to 150 μm.

5. The composition for preventing or treating periodontal disease according to claim 1, wherein, The bulk density of the metronidazole is 0.2 to 0.5 g / cm³. 3 .

6. A dental compound antibiotic ointment composition, wherein, The dental compound antibiotic ointment composition comprises minocycline, metronidazole, a matrix, an emulsifier, a viscosity modifier, a stabilizer, and an antioxidant.

7. The dental compound antibiotic ointment composition according to claim 6, wherein, The minocycline is used at a ratio of 0.1 to 2% by weight of the total weight of the ointment. The metronidazole is used at a ratio of 0.1% to 50% by weight of the total weight of the ointment.

8. The dental compound antibiotic ointment composition according to claim 6, wherein, The base is used at a ratio of 5% to 25% by weight of the total weight of the ointment. The matrix comprises any one or more of the following groups: concentrated glycerol, polyethylene glycol 400, polyethylene glycol 4000, propylene glycol, 1,3-propanediol, isopentylene glycol, pentylene glycol, hexanediol, butylene glycol, diethylene glycol, dipropylene glycol, diglycerol, erythritol, arabinitol, arabinitol, sorbitol, mannitol, xylitol, galactitol, glucose, fructose, xylose, trehalose, maltose, sucrose, and lactose.

9. The dental compound antibiotic ointment composition according to claim 6, wherein, The emulsifier is used at a ratio of 20 to 50% by weight of the total weight of the ointment. The emulsifier comprises any one or more selected from the group consisting of glyceryl monostearate, glyceryl monooleate, glyceryl monolaurate, glyceryl monopalmitate, acetylated glyceryl monostearate, white petrolatum, liquid paraffin, paraffin, stearic acid, cetearyl alcohol, isopropyl myristate, and cetyl palmitate.

10. The dental compound antibiotic ointment composition according to claim 1, wherein, The viscosity modifier is used at a ratio of 1 to 20% by weight of the total weight of the ointment. The viscosity modifier comprises any one or more of the following: mineral oil, sesame oil, tea tree oil, avocado oil, castor oil, rapeseed oil, coffee oil, corn oil, jojoba oil, kaya oil, flaxseed oil, macadamia oil, olive oil, peanut oil, rapeseed oil, cottonseed oil, rice bran oil, safflower seed oil, camellia oil, sunflower seed oil, soybean oil, shea butter, green tea seed oil, borage oil, walnut oil, evening primrose oil, lanolin oil, calendula oil, rosehip oil, coconut oil, mustard oil, palm oil, palm kernel oil, apricot kernel oil, grape seed oil, castor oil, poppy seed oil, argan oil, flaxseed oil, almond oil, hazelnut oil, hemp seed oil, and pumpkin seed oil.

11. The dental compound antibiotic ointment composition according to claim 1, wherein, The stabilizer is used at a ratio of 1 to 8% by weight of the total weight of the ointment. The stabilizer contains magnesium chloride.

12. The dental compound antibiotic ointment composition according to claim 1, wherein, The antioxidant is used at a ratio of less than 2% by weight of the total weight of the ointment. The antioxidant includes ascorbyl palmitate.

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