Composition for prevention or treatment of periodontal disease and dental composite antibiotic ointment composition

Abstract

The present invention relates to a composition for the prevention or treatment of periodontal disease and a dental composite antibiotic ointment composition. The composition for the prevention or treatment of periodontal disease according to the present invention comprises minocycline and metronidazole as active ingredients.

Description

Composition for the prevention or treatment of periodontal disease and dental complex antibiotic ointment composition

[0001] The present invention relates to a composition for preventing or treating periodontal disease and a dental complex antibiotic ointment composition.

[0002] Periodontal disease is caused by bacterial infection in the gums, teeth, and implant areas due to poor oral hygiene. Periodontitis primarily affects natural teeth, while peri-implantitis occurs around dental implants. Severe periodontitis can lead to increased periodontal pocket depth, bleeding, gum erosion, and bone loss.

[0003] Peri-implantitis is similar to periodontitis, but unlike periodontitis, the lesion extends to the periapical region and presents with acute inflammatory symptoms. Furthermore, the oral microbiota distribution of periodontitis differs from that of periodontitis, leading to redness, swelling, mucosal hypertrophy, abscesses, bleeding, increased periodontal pocket depth, and increased bone loss at the implant site.

[0004] Although the symptoms of periodontitis and peri-implantitis differ, treatment methods can be divided into surgical and non-surgical, and similar approaches can be applied to each condition. Surgical treatments for periodontitis include gum incisions, scaling, and root planing to remove inflammation and plaque, and reshape the gingiva. For peri-implantitis, similar to periodontitis, inflammation is treated, and biofilm on the implant surface may be removed using lasers or nickel-titanium brushes. For both types of periodontal disease, bone grafting may be performed if necessary to restore lost gum bone.

[0005] Nonsurgically, both periodontitis and peri-implantitis are treated with antibiotics. Currently, antibiotic ointments containing minocycline hydrochloride are used for nonsurgical treatment. These ointments are injected into the periodontal pockets after removing calculus, plaque, and inflammation, directly injecting antibiotics. This provides a localized treatment. Numerous clinical trials have demonstrated the effectiveness of commercially available ointments in treating periodontitis.

[0006] However, in the treatment of peri-implantitis, it is difficult to treat all oral microorganisms for the symptom with the existing single-ingredient dental ointment, and there are pathological differences, so there are limitations in applying existing treatment drugs as a clear non-surgical treatment method for peri-implantitis, and it is necessary to seek a direction to apply other drugs.

[0007] Therefore, to address the problems of existing single-component antibiotic dental ointments, the present invention developed an antibiotic ointment composition combining two antibiotics. The present invention aims to provide a non-surgical treatment for periodontal diseases such as periodontitis and peri-implantitis more effectively 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.

[0009] Patent Document 2: Maruyama, N., Maruyama, F., Takeuchi, Y. et al. Intraindividual variation in core microbiota in peri-implantitis and periodontitis. Sci Rep 4, 6602 (2014).

[0010] Patent Document 3: Heitz-Mayfield LJ, Lang NP. Surgical and nonsurgical periodontal therapy. Learned and unlearned concepts. Periodontol 2000. 2013 Jun;62(1):218-31. doi: 10.1111 / prd.12008. PMID: 23574468.

[0011] Patent Document 4: Republic of Korea Patent Publication No. 10-0252699

[0012] Patent Document 5: Berglundh T, Zitzmann NU, Donati M. Are peri-implantitis lesions different from periodontitis lesions? J Clin Periodontol. 2011 Mar;38 Suppl 11:188-202. doi: 10.1111 / j.1600-051X.2010.01672.x. PMID: 21323715.

[0013] 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 Relat Res. 2014 Jun;16(3):401-11. doi: 10.1111 / cid.12001. Epub 2012 Sep 11. PMID: 22967131.

[0014] In order to solve the problems of the above-mentioned prior art, the present inventors intend to provide a composition for preventing or treating periodontal disease and a dental complex antibiotic ointment composition containing minocycline and metronidazole as active ingredients.

[0015] The present invention provides a composition for preventing or treating periodontal disease, comprising minocycline and metronidazole as active ingredients, in order to solve the above-mentioned problem.

[0016] In addition, in the present composition, the minocycline can provide a composition for preventing or treating periodontal disease, which includes minocycline hydrochloride as an active ingredient and the metronidazole can provide metronidazole benzoate as an active ingredient.

[0017] In addition, in the present composition, the minocycline and the metronidazole can be mixed in a weight ratio of 1:1 to 1:25 to provide a composition for preventing or treating periodontal disease.

[0018] In addition, in the present composition, the metronidazole particle size (D90) can provide a composition for preventing or treating periodontal disease, wherein the particle size is 5 to 150 μm.

[0019] In addition, in the present composition, the bulk density of the metronidazole is 0.2 to 0.5 g / cm 3 A composition for preventing or treating periodontal disease can be provided.

[0020] In addition, in another embodiment of the present invention, a dental composite antibiotic ointment composition comprising minocycline, metronidazole, a base, an emulsifier, a viscosity modifier, a stabilizer, and an antioxidant is provided.

[0021] In addition, in the present ointment, a dental complex antibiotic ointment composition can be provided in which the minocycline is used in a proportion of 0.1 to 2% by weight of the total weight of the ointment, and the metronidazole is used in a proportion of 0.1 to 50% by weight of the total weight of the ointment.

[0022] In addition, in the present ointment, the base is used in a proportion of 5 to 25% by weight of the total weight of the ointment, and a dental complex antibiotic ointment composition can be provided, which includes at least one selected from the group consisting of concentrated glycerin, polyethylene glycol 400, polyethylene glycol 4000, propylene glycol, 1,3-propanediol, isoprene glycol, pentylene glycol, hexylene glycol, butylene glycol, diethylene glycol, dipropylene glycol, diglycerol, erythritol, arabitol, adonitol, sorbitol, mannitol, xylitol, dulcitol, glucose, fructose, xylose, trehalose, maltose, saccharose, and lactose.

[0023] In addition, in the present ointment, the emulsifier is used in a proportion of 20 to 50% by weight of the total weight of the ointment, and a dental complex antibiotic ointment composition can be provided, which includes at least one selected from the group consisting of glyceryl monostearate, glyceryl monooleate, glyceryl monolaurate, glyceryl monopalmitate, acetylated monoglyceride, white petrolatum, liquid paraffin, paraffin, stearic acid, cetostearyl alcohol, isopropyl myristate, and cetyl palmitate.

[0024] In addition, in the present ointment, the viscosity modifier is used in a ratio of 1 to 20% by weight of the total weight of the ointment, and a dental complex antibiotic ointment composition comprising at least one selected from the group consisting of mineral oil, sesame oil, tea tree oil, avocado oil, castor oil, canola oil, coffee oil, corn oil, jojoba oil, kaya oil, linseed oil, macadamia oil, olive oil, peanut oil, rapeseed oil, cottonseed oil, rice bran oil, safflower 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 olein 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, hempseed oil, and pumpkin seed oil. Can provide.

[0025] In addition, in the present ointment, the stabilizer is used in a proportion of 1 to 8% by weight of the total weight of the ointment, and a dental complex antibiotic ointment composition including magnesium chloride can be provided.

[0026] In addition, the present invention can provide a dental complex antibiotic ointment composition including ascorbyl palmitate, wherein the antioxidant is used in a proportion of 2% by weight or less of the total weight of the ointment.

[0027] The composition for preventing or treating periodontal disease according to the present invention has the effect of treating periodontal disease, including peri-implantitis and periodontitis, which could not be treated with single-component antibiotics, by removing bacteria caused by the disease using a combination of antibiotics.

[0028] The following drawings attached to this specification illustrate preferred embodiments of the present invention and, together with the detailed description of the invention, serve to further understand the technical idea of ​​the present invention, and therefore, the present invention should not be interpreted as being limited to matters described in such drawings.

[0029] Figure 1 is a graph showing the results of a syringe injection force test of a dental composite antibiotic ointment composition according to one embodiment of the present invention.

[0030] Figures 2 and 3 are graphs showing the results of a syringe injection force test according to comparative examples of the present invention.

[0031] FIG. 4 is a drawing showing the results of an adhesive test on artificial saliva of a dental composite antibiotic ointment composition according to one embodiment of the present invention and a single-component ointment, Comparative Example 1.

[0032] FIG. 5 is a drawing showing the viscosity and properties of an ointment composition according to the apparent density of metronidazole benzoate according to one embodiment of the present invention.

[0033] Figure 6 is a graph showing the results of measuring the periodontal pocket depth restoration rate according to treatment with an ointment composition according to one embodiment of the present invention and Comparative Example 1, which is a single-component ointment.

[0034] Figure 7 is a drawing measuring changes in the presence or absence of inflammation according to treatment with an ointment composition according to one embodiment of the present invention and Comparative Example 1, which is a single-component ointment.

[0035] The present invention provides a composition for preventing or treating periodontal disease, comprising minocycline and metronidazole as active ingredients, in order to solve the above-mentioned problem.

[0036] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. The following embodiments are provided to sufficiently convey the spirit of the present invention to those skilled in the art. The present invention is not limited to the embodiments presented herein and may be embodied in other forms. To clarify the present invention, the drawings may omit portions irrelevant to the description, and the sizes of components may be slightly exaggerated to facilitate understanding.

[0037] The terminology used herein is for the purpose of describing specific embodiments only and is not intended to limit the present invention. Furthermore, the singular forms "a," "an," and "the" as used herein include plural forms unless the context clearly dictates otherwise. Furthermore, the terms "comprise" and "include" as used herein specify a particular feature, region, integer, step, operation, element, or component, but do not exclude the addition of other features, regions, integers, steps, operations, elements, or components.

[0038] In the present invention, terms such as first, second, etc. are used to describe various components, and the terms are used only for the purpose of distinguishing one component from another.

[0039] Furthermore, the terminology used herein is merely for the purpose of describing exemplary embodiments and is not intended to limit the present invention. The singular expression includes the plural expression unless the context clearly indicates otherwise. In this specification, it should be understood that the terms "comprise," "include," or "have" indicate the presence of a feature, number, step, component, or combination thereof, but do not preclude the possibility of the presence or addition of one or more other features, numbers, steps, components, or combinations thereof.

[0040] The present invention is susceptible to various modifications and takes various forms. Specific embodiments are illustrated and described in detail below. However, this is not intended to limit the present invention to specific disclosed forms, but rather to encompass all modifications, equivalents, and alternatives falling within the spirit and technical scope of the present invention.

[0041]

[0042] Hereinafter, the composition for preventing or treating periodontal disease and the dental complex antibiotic ointment composition according to the present invention will be sequentially described in detail.

[0043] According to one embodiment of the present invention, the composition for preventing or treating periodontal disease comprises minocycline and metronidazole as active ingredients.

[0044] The above minocycline and metronidazole can be used as antibiotics for the prevention or treatment of periodontal disease. By using metronidazole in combination with the widely used minocycline, bacteria that single-ingredient antibiotics cannot treat can be treated.

[0045] For example, the minocycline may contain minocycline hydrochloride as an active ingredient, and the metronidazole may contain metronidazole benzoate as an active ingredient.

[0046] The above minocycline and the above metronidazole can be used in a mixed weight ratio of 1:1 to 1:25.

[0047] If the mixing ratio of the above minocycline and the above metronidazole is less than 1:1, the drug concentration is too low to have a therapeutic effect, and if it exceeds 1:25, there is a problem in terms of maintaining the properties in the ointment formulation.

[0048] The above metronidazole particle size (D90) may be 5 to 150 μm.

[0049] When the particle size of the metronidazole is less than 5㎛, the viscosity of the composition becomes too high, dispersion within the composition is not achieved well, and the composition clumps together, making it difficult to obtain the effect of the metronidazole. When the particle size exceeds 150㎛, the viscosity of the composition becomes low, and when a syringe nozzle of a standard applicable to a periodontal pocket (nozzle diameter 0.4 to 0.6 mm) is applied, there is a problem of clogging.

[0050] Preferably, the metronidazole particle size (D90) may be 5 to 100 μm, the metronidazole particle size (D90) may be 10 to 90 μm, and the metronidazole particle size (D90) may be 20 to 50 μm.

[0051] The density of the above metronidazole is 0.2 to 0.5 g / cm 3 It could be.

[0052] The density of the above metronidazole is 0.2 g / cm 3 If it is less than 0.5 g / cm, the viscosity of the composition or ointment is too high, and the spreadability is reduced when used as an ointment, and the density of the metronidazole is less than 0.5 g / cm. 3 If it is excessive, the viscosity is too low, so there is a problem that it does not spread when used as an ointment, does not adhere to the skin, and falls off.

[0053] The composition for preventing or treating periodontal disease of the present invention can be formulated in the form of an ointment.

[0054] According to one embodiment of the present invention, the dental composite antibiotic ointment composition comprises minocycline, metronidazole, a base, an emulsifier, a viscosity modifier, a stabilizer, and an antioxidant.

[0055] The above minocycline is used in a proportion of 0.1 to 2% by weight of the total weight of the ointment, and the above metronidazole can be used in a proportion of 0.1 to 50% by weight of the total weight of the ointment, and it is preferable to add them in an effective amount in order to exhibit an effective effect for preventing or treating periodontal disease.

[0056] The composition for preventing or treating periodontal disease of the present invention may use a base so that it can be formulated in the form of an ointment.

[0057] The above-mentioned base is used in a proportion of 5 to 25% by weight of the total weight of the ointment, and may include at least one selected from the group consisting of concentrated glycerin, polyethylene glycol 400, polyethylene glycol 4000, propylene glycol, 1,3-propanediol, isoprene glycol, pentylene glycol, hexylene glycol, butylene glycol, diethylene glycol, dipropylene glycol, diglycerol, erythritol, arabitol, adonitol, sorbitol, mannitol, xylitol, dulcitol, glucose, fructose, xylose, trehalose, maltose, saccharose, and lactose.

[0058] The above emulsifier is used in a proportion of 20 to 50% by weight of the total weight of the ointment, and may include at least one selected from the group consisting of glyceryl monostearate, glyceryl monooleate, glyceryl monolaurate, glyceryl monopalmitate, acetylated monoglyceride, white petrolatum, liquid paraffin, paraffin, stearic acid, cetostearyl alcohol, isopropyl myristate, and cetyl palmitate.

[0059] For example, the above-mentioned agent and the above-mentioned emulsifier can be mixed and used in a weight ratio of 1:1 to 1:4.

[0060] When the weight ratio of the base and the emulsifier is less than 1:1, the viscosity of the dental composite antibiotic ointment composition is too high, which causes a problem in that it cannot be dispensed through a syringe. When the weight ratio of the base and the emulsifier is more than 1:4, the viscosity is too low, which causes a problem in that it does not spread when used as an ointment, does not adhere to the skin, and falls off.

[0061] The viscosity modifier is used in a ratio of 1 to 20% by weight of the total weight of the ointment, and may include at least one selected from the group consisting of mineral oil, sesame oil, tea tree oil, avocado oil, castor oil, canola oil, coffee oil, corn oil, jojoba oil, kaya oil, linseed oil, macadamia oil, olive oil, peanut oil, rapeseed oil, cottonseed oil, rice bran oil, safflower 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 olein 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, hempseed oil, and pumpkin seed oil.

[0062] The above stabilizer is used in a proportion of 1 to 8% by weight of the total weight of the ointment and may include magnesium chloride.

[0063] The above antioxidant is used in a proportion of 2% by weight or less of the total weight of the ointment, and may include ascorbyl palmitate.

[0064] The above composition may preferably be a pharmaceutical composition, and more preferably a composition having a formulation in the form of an ointment.

[0065] The composition may be provided as a pharmaceutical composition comprising the active ingredient alone or including one or more pharmaceutically acceptable carriers, excipients or diluents.

[0066] The term “pharmaceutically acceptable” as used herein means that the composition exhibits properties that are not toxic to cells or humans exposed to the composition.

[0067] Furthermore, the composition may be provided in combination with a conventionally known periodontal disease treatment agent. That is, the composition may be administered in combination with a known compound having a preventive or therapeutic effect on periodontal disease.

[0068] The above "administration" means introducing a given substance to an individual through an appropriate method, and "individual" means any animal, including rats, mice, livestock, etc., including humans, that has developed or may develop periodontal disease. A specific example may be a mammal, including humans.

[0069] The preferred dosage of the composition above varies depending on the patient's condition and weight, the severity of the disease, the drug form, the route of administration, and the duration of the administration, but can be appropriately selected by those skilled in the art. However, for a desirable effect, the composition is preferably administered at 0.01 to 1000 mg / kg / day, preferably 0.1 to 500 mg / kg / day, but is not limited thereto. The administration may be administered once a day or divided into several doses. The dosage is not limited in any way.

[0070]

[0071] Hereinafter, the present invention will be described in more detail through examples and experimental examples.

[0072] However, the following examples and experimental examples are only illustrative of the present invention, and the content of the present invention is not limited to the following examples and experimental examples.

[0073]

[0074] Example 1

[0075] According to the composition ratio in Table 1 below, a dental composite antibiotic ointment composition was prepared.

[0076] Ingredients Content (wt%) Role Minocycline hydrochloride 2.0 Antibiotic Metronidazole benzoate 40.2 Antibiotic Concentrated glycerin 25.0 Base Glyceryl monooleate 25.0 Emulsifier Sesame oil 3.0 Viscosity regulator Magnesium chloride 4.0 Stabilizer Ascorbyl palmitate 0.8 Antioxidant Total 100-

[0077] Each ointment was added to the syringe of the dental composite antibiotic ointment composition manufactured according to the above Example 1, and the injection force was measured. As a comparative example, the syringe injection force of the product of Company A (Comparative Example 1) and the product of Company B (Comparative Example 2), which are commercially available as single-ingredient minocycline products, was compared and measured.

[0078] Here, the composition of Comparative Example 1 includes minocycline hydrochloride as a main component, sodium alginate, plastibase, hypromellose 2910 and polysorbate 80 as bases, chitosan as an antioxidant, sodium carboxymethylcellulose and carbomer as a thickener, and the composition of Comparative Example 2 includes minocycline hydrochloride as a main component, hydroxyethyl cellulose and ammonium methacrylate copolymer as sustained-release agents, triacetin as a solubilizer, magnesium chloride as a stabilizer, and concentrated glycerin as a solvent.

[0079] Each syringe was filled with 1 ml of the dental compound antibiotic ointment composition manufactured according to Example 1, Comparative Examples 1 and 2 in a plastic syringe container. The syringe was mounted on the test fixture of a small tabletop precision universal testing machine, and a vertical downward force was applied to the syringe plunger at a rate of 100±5 mm / min using a force gauge. The force required to dispense the ointment in the syringe was measured, and the test machine was stopped at 10% or less of the nominal capacity in the syringe, the maximum load was recorded, and it was confirmed whether the ointment was easily dispensed from the syringe container. A load value of 20 N or less was considered pass (○ judgment), between 20 and 25 N was considered appropriate (Δ), and over 25 N was considered fail (× judgment). Other results are shown in Table 2 and Figures 1 to 3 below.

[0080] Fig. 1 is a graph showing the results of a syringe injection force test of a dental composite antibiotic ointment composition according to one embodiment of the present invention. Figs. 2 and 3 are graphs showing the results of a syringe injection force test according to Comparative Examples 1 and 2 of the present invention.

[0081] Syringe injection force (N) Evaluation results Example 115.22 ± 0.57O Comparative example 128.49 ± 0.98X Comparative example 235.74 ± 1.28X

[0082] The adhesiveness of the dental composite antibiotic ointment composition manufactured according to Example 1 and Comparative Example 2 as a comparative example to artificial saliva was tested three times, and the results are shown in Table 3 and FIG. 4 below. FIG. 4 is a drawing showing the results of an adhesiveness test on artificial saliva of the dental composite antibiotic ointment composition according to one embodiment of the present invention and Comparative Example 2, which is a single-component ointment.

[0083] Residue (%)Average Residue (%)Example 1-193.4791.27Example 1-292.24Example 1-388.11Comparative Example 2-177.53275.88Comparative Example 2-278.723Comparative Example 2-371.374

[0084] Examples 2 to 4, Comparative Examples 1 to 4

[0085] In the above Example 1, the mixing ratio of concentrated glycerin and glyceryl monooleate corresponding to the base and emulsifier was adjusted as shown in Table 4 below to prepare a dental composite antibiotic ointment composition.

[0086] Concentrated glycerin: Glyceryl monooleate weight ratio Example 11:1 Example 21:1.5 Example 31:4 Comparative Example 3 100% glyceryl monooleate Comparative Example 4 100% concentrated glycerin Comparative Example 51.5:1 Comparative Example 64:1

[0087] In addition, the viscosity of the dental composite antibiotic ointment compositions manufactured according to Examples 1 to 3 and Comparative Examples 3 to 6 was measured, and the injection force was measured after adding each ointment to a syringe, and the results are shown in Table 5 below.

[0088] Viscosity (cPs) Syringe injection force evaluation results Example 1 10,338.3 ± 289.3 Δ Example 27,716.7 ± 278.3 0 Example 37,391.7 ± 953.3 0 Comparative Example 3--Comparative Example 4 13,877.3 ± 518.7 X Comparative Example 5 13,514.0 ± 1,518 X Comparative Example 6 13,939.3 ± 1,729.3 X

[0089] Examples 4 to 6, Comparative Examples 7 and 8

[0090] In the above Example 1, the bulk density of metronidazole benzoate was adjusted as shown in Table 6 below to prepare a dental composite antibiotic ointment composition, and the viscosity thereof was measured, and the results are shown in Table 6 and Fig. 5.

[0091] FIG. 5 is a drawing showing the viscosity and properties of an ointment composition according to the apparent density of metronidazole benzoate according to one embodiment of the present invention.

[0092] Apparent density (g / cm) 3 ) Viscosity (cPs) Comparative Example 70.15514,052 Exemplary Example 40.2448,130.3 Exemplary Example 50.3456,324.7 Exemplary Example 60.4126,792.3 Comparative Example 80.6854,504.7

[0093] In addition, the periodontal pocket depth restoration rate according to treatment with the dental composite antibiotic ointment composition manufactured according to Example 5 and Comparative Example 8 was tested, and the results are shown in Fig. 6.

[0094] Figure 6 is a graph showing the results of measuring the periodontal pocket depth restoration rate according to treatment with an ointment composition according to one embodiment of the present invention and Comparative Example 1, which is a single-component ointment.

[0095] Referring to Table 6 and Figure 6, the graph is shown in blue for the apparent density of 0.35 corresponding to Example 5, and it can be seen that the periodontal depth restoration rate increases rapidly over time, showing a restoration rate of approximately 78.90% after 3 weeks, and a high restoration rate of 83.9% after 12 weeks.

[0096] In contrast, in the case of the apparent density of 0.68 corresponding to Comparative Example 8, the graph is shown in gray, and it was found that the recovery rate was 68.9% after 12 weeks over time, but the periodontal pocket depth recovery rate was shown at a significantly lower rate than that of Example 5.

[0097] In addition, in the case of Comparative Example 1 using only minocycline, the graph is shown in orange, and it was found that the periodontal pocket depth recovery rate was superior to the case without ointment treatment (shown in yellow), but the recovery rate was inferior to that of the combination antibiotic ointment, and in particular, it showed a significantly lower recovery rate than that of Example 5.

[0098] In addition, changes in inflammation were observed according to treatment with the dental composite antibiotic ointment composition manufactured according to Example 5 and Comparative Example 8, and the results are shown in Fig. 7.

[0099] Figure 7 is a drawing measuring changes in the presence or absence of inflammation according to treatment with an ointment composition according to one embodiment of the present invention and Comparative Example 1, which is a single-component ointment.

[0100] Referring to Table 6 and Figure 7, in the case of the apparent density of 0.35 corresponding to Example 5, it was confirmed that most of the inflammation had disappeared around the 2nd to 3rd week, in the case of the apparent density of 0.68 corresponding to Comparative Example 6, it was confirmed that the inflammation had disappeared after the 4th week, and in the case of Comparative Example 1 using minocycline as a single agent, it was confirmed that the inflammation had disappeared after the 8th week, and in the case of the untreated group, it was confirmed that the inflammation had continued to persist.

[0101] The above description of the present invention is for illustrative purposes only, and those skilled in the art will readily appreciate that the present invention can be readily modified into other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single entity may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined manner.

[0102] The scope of the present invention is indicated by the claims described below rather than the detailed description above, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be interpreted as being included in the scope of the present invention.

Claims

1. A composition for preventing or treating periodontal disease containing minocycline and metronidazole as active ingredients.

2. In paragraph 1, A composition for preventing or treating periodontal disease, wherein the minocycline comprises minocycline hydrochloride as an active ingredient, and the metronidazole comprises metronidazole benzoate as an active ingredient.

3. In paragraph 1, A composition for preventing or treating periodontal disease, wherein the minocycline and the metronidazole are mixed and used in a weight ratio of 1:1 to 1:

25.

4. In paragraph 1, A composition for preventing or treating periodontal disease, wherein the above metronidazole particle size (D90) is 5 to 150 μm.

5. In paragraph 1, The apparent density (bulk density) of the above metronidazole is 0.2 to 0.5 g / cm 3 A composition for preventing or treating periodontal disease.

6. A dental complex antibiotic ointment composition comprising minocycline, metronidazole, a base, an emulsifier, a viscosity modifier, a stabilizer and an antioxidant.

7. In paragraph 6, The above minocycline is used in a proportion of 0.1 to 2% by weight of the total weight of the ointment. A dental complex antibiotic ointment composition wherein the above metronidazole is used in a proportion of 0.1 to 50% by weight of the total weight of the ointment.

8. In paragraph 6, The above-mentioned agent is used in a proportion of 5 to 25% by weight of the total weight of the ointment. A dental complex antibiotic ointment composition comprising at least one selected from the group consisting of concentrated glycerin, polyethylene glycol 400, polyethylene glycol 4000, propylene glycol, 1,3-propanediol, isoprene glycol, pentylene glycol, hexylene glycol, butylene glycol, diethylene glycol, dipropylene glycol, diglycerol, erythritol, arabitol, adonitol, sorbitol, mannitol, xylitol, dulcitol, glucose, fructose, xylose, trehalose, maltose, saccharose and lactose.

9. In paragraph 6, The above emulsifier is used in a proportion of 20 to 50% by weight of the total weight of the ointment. A dental complex antibiotic ointment composition comprising at least one selected from the group consisting of glyceryl monostearate, glyceryl monooleate, glyceryl monolaurate, glyceryl monopalmitate, acetylated monoglyceride, white petrolatum, liquid paraffin, paraffin, stearic acid, cetostearyl alcohol, isopropyl myristate, and cetyl palmitate.

10. In paragraph 1, The above viscosity modifier is used in a proportion of 1 to 20% by weight of the total weight of the ointment. A dental complex antibiotic ointment composition comprising at least one selected from the group consisting of mineral oil, sesame oil, tea tree oil, avocado oil, castor oil, canola oil, coffee oil, corn oil, jojoba oil, kaya oil, linseed oil, macadamia oil, olive oil, peanut oil, rapeseed oil, cottonseed oil, rice bran oil, safflower 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 olein 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, hempseed oil, and pumpkin seed oil.

11. In paragraph 1, The above stabilizer is used in a proportion of 1 to 8% by weight of the total weight of the ointment. A dental complex antibiotic ointment composition containing magnesium chloride.

12. In paragraph 1, The above antioxidant is used in a proportion of less than 2% by weight of the total weight of the ointment. A dental complex antibiotic ointment composition comprising ascorbyl palmitate.

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