KR101406106B1 - Locally applied composition of sustained-release for treating periodontal diseases - Google Patents

Abstract

The present invention relates to a sustained periodontal therapeutic composition for topical administration, and more particularly, to a composition for treating periodontal disease, which comprises an antibiotic, a polyacrylic acid polymer, a water-soluble polymer, an antioxidant component and an ointment base, It is possible to treat periodontitis continuously over a long period of time. When the antibiotic treatment is finished and the treatment of periodontitis is completed, the composition for treating periodontal disease is completely decomposed, The present invention relates to an antimicrobial composition for the treatment of persistent periodontitis for topical administration which does not require the removal of a separate periodontal therapeutic composition.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a composition for sustaining periodontal disease,

The present invention relates to a sustained periodontal therapeutic composition for topical administration, and more particularly, to a composition for treating periodontal disease, which comprises an antibiotic, a polyacrylic acid polymer, a water-soluble polymer, an antioxidant component and an ointment base, It is possible to treat periodontitis continuously over a long period of time. When the antibiotic treatment is finished and the treatment of periodontitis is completed, the composition for treating periodontal disease is completely decomposed, The present invention relates to an antimicrobial composition for the treatment of persistent periodontitis for topical administration which does not require the removal of a separate periodontal therapeutic composition.

There are many kinds of diseases in the oral cavity including teeth. Periodontal disease, which is caused by teeth, is often referred to as a style. Gingivitis and periodontitis are classified according to the severity of the disease. It is a relatively light and fast-acting periodontal disease called gingivitis that is limited to gingiva or soft tissue, and it is called periodontitis when the inflammation progresses to the gums and the gums.

Symptoms of periodontal disease are usually caused by gums, bleeding and bad breath. Pathogens that cause periodontal disease are gram-negative bacteria, an anaerobic bacterium, that secrete collagenase, collagen that supports the dentin is destroyed, and periodontal bone supporting teeth is dissolved Periodontal ligaments are separated to form the periodontal pouch, and in severe cases, progressive periodontal disease develops.

It is best to prevent periodontitis from occurring first. If you have already developed periodontitis, you need to remove pathogens that cause periodontal disease. To remove the pathogens that cause periodontal disease, you need to take antibiotics and inflammation It is necessary to take medication such as anti-inflammatory medication to relieve.

Antimicrobial therapy for the treatment of periodontitis and anti-inflammatory medications such as anti-inflammatory medications are usually administered by oral administration. Drug therapy using such oral administration is not effective during the passage of the drug through the gastrointestinal tract, Drugs administered by metabolism after being absorbed into the body before they reach can change.

On the other hand, oral administration of a drug for the treatment of periodontitis requires an excessive amount of drug because the actual drug has a low concentration of the drug reaching the periodontal tissue. Overdosage of these antimicrobial drugs over a long period of time may result in the appearance of resistant bacteria to antibiotic drugs or side effects in other organs of the body.

Accordingly, the therapeutic agent for treating periodontitis is mainly applied to an area of periodontal disease in the form of an ointment or a liquid.

As mentioned above, the gingivitis treatment agent is actively developed in the form of ointments and liquid preparations for the treatment of periodontitis for local administration, which is directly administered to the periodontal tissue in which periodontitis occurs. However, in this case, due to the saliva, Since the gingivitis therapeutic composition can easily be decomposed or the drug can not stay in the lesion site where the gingivitis develops for a long time, it is often necessary to administer and / or apply the gingivitis treatment drug to the area where periodontitis occurs.

As a prior art related to the present invention, a biodegradable polymer microsphere containing an antibiotic and a water-soluble polymer are mixed with distilled water to prepare a hydrogel, which is then molded into a film or strip, There is a description of a composition for treating periodontal disease for topical administration which can continuously obtain a drug effect.

In Korean Patent No. 10-0232645, a microsphere made of a biodegradable polymer contains a physiologically active substance effective for the treatment of periodontitis, which is mixed with a water-soluble polymer to form a film or a strip In addition, it is possible to obtain a sustained drug effect over a long period of time by coating the preparation with an aqueous solution of a metal cation salt, and a topical dosage-type biodegradable sustained-release There is a description of a composition for treating periodontal disease.

However, the above-mentioned prior arts require a special manufacturing apparatus and a manufacturing cost increase due to a copolymer in order to manufacture a microsphere, which is a sustained-release preparation. In addition, there is a possibility of residual organic solvent used for dissolving the polymer. In addition, they have an inconvenience that if the decomposition rate is significantly slower than the drug efficacy maintenance period, it should also be removed after the treatment period.

The present invention and the prior art are different from each other in terms of the constitution and / or the effect of the invention because the main technical features of the invention are different from each other.

It is an object of the present invention to provide a sustained periodontal therapeutic composition for topical administration.

The present invention can provide a sustained periodontal therapeutic composition for topical administration comprising an antibiotic, a polyacrylic acid polymer, a water-soluble polymer, an antioxidant component and an ointment base.

The therapeutic composition for periodontitis including the antibiotic, polyacrylic acid polymer, water-soluble polymer, antioxidant component and ointment base of the present invention can be administered locally at the site where periodontitis occurs, and the therapeutic composition applied to the site where periodontitis occurs is over time It is possible to treat periodontitis continuously for a long period of time.

In addition, the composition for treating periodontal disease according to the present invention is a composition for treating periodontal disease, wherein the composition for treating periodontitis is completely decomposed at the end of the treatment of periodontitis after the administration of the antibiotic, The antimicrobial composition for treating persistent periodontitis can be provided.

1 is a graph showing a drug release pattern of minocycline hydrochloride in the agent for treating periodontal disease of Example 11, the agent for treating periodontitis of Example 15, and the agent for treating periodontitis of Example 17.
FIG. 2 is a graph showing drug release rates of minocycline hydrochloride over time in the periodontitis treatment agent of Example 11, the periodontitis treatment agent of Example 15, and the periodontal treatment agent of Example 17. FIG.
3 is a comparative photograph of the stability of the agent for treating periodontitis in Example 11 and the agent for treating periodontitis in Example 19;

The present invention represents a sustained periodontal therapeutic composition for topical administration.

The present invention represents a sustained periodontal therapeutic composition for topical administration comprising an antibiotic, a polyacrylic acid polymer, a water soluble polymer, an antioxidant component and an ointment base.

The present invention relates to a sustained periodontal therapeutic composition composition for topical administration comprising 2 to 10% by weight of an antibiotic, 2 to 50% by weight of a polyacrylic acid polymer, 2 to 50% by weight of a water-soluble polymer, 0.04 to 10% .

The antibiotics used in the above can be used for the treatment of periodontitis.

Wherein the antibiotic is selected from the group consisting of minocycline, tetracycline, doxycycline, chlorohexidine, ofloxacin, tinidazole, ketonazole, metronidazole, (metronidazole) may be used.

If two or more antibiotics are used, antibiotic mixtures mixed at the same weight ratio may be used.

In the above, minocycline can be used as the antibiotic.

In the above, the polyacrylic acid polymer plays a role in controlling antibiotics of the periodontal remedy.

The polyacrylic acid polymer may be a carbomer series.

The polyacrylic acid polymer may be at least one selected from the group consisting of carbomer 940, carbomer 974, carbomer 934, carbomer 980, carbomer 971 and carbomer 941.

In the case of using a mixed component in which two polyacrylic acid polymers are mixed, a polyacrylic acid polymer mixed at a weight ratio of 1: 9 to 9: 1 may be used.

In the case of using a mixed component in which two kinds of polyacrylic acid polymers are mixed, the polyacrylic acid polymer mixed at the same weight ratio can be used.

When three or more polyacrylic acid polymers are used, polyacrylic acid polymers mixed at the same weight ratio can be used.

The above-mentioned carbomer is harmless to human body and is a polymer substance frequently used in foods, cosmetics, and pharmaceuticals, and has a weight average molecular weight of 450,000 to 4,000,000. In addition, the carbomer is not affected by high temperatures, so it has high temperature stability, is safe for microorganisms, has no toxicity or irritation, and has little viscosity change with temperature. Particularly a biocompatible substance, a sustained-release base, a suspending agent, a tablet binding agent, an increasing agent and the like.

The carbomer used as the polyacrylic acid polymer may be used in an amount of 2 to 50% based on the total weight of the composition for treating periodontal disease.

In the above, the water-soluble polymer enhances the stickiness of the composition for treating periodontitis, thereby preventing the gingivitis therapeutic composition from being washed out due to saliva, secretions, foreign matter, and food produced in the oral cavity.

The water-soluble polymer may be selected from the group consisting of sodium alginate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose (sodium CMC), hydroxypropylethylcellulose Hydroxypropyl ethylcellulose, dextran, and dextrin pectin may be used.

The water-soluble polymer may be used in an amount of 2 to 50% based on the total weight of the composition for treating periodontitis.

Some of the antibiotics are sensitive to light, and the polyacrylic acid polymer has a property of decreasing viscosity upon exposure to light and discoloring during long-term storage, so that the stability of the antibiotic and / or polyacrylic acid polymer is inhibited, Antioxidant ingredients may be used. In addition, anti-inflammatory effects of antioxidants in the treatment of periodontal inflammation can be expected to be effective.

The antioxidant component may be at least one selected from the group consisting of chitosan, vitamin C, tocopherol, sitosterol-containing extract, and corn-deficient quantitative extract.

The antioxidant component may be used in an amount of 0.04 to 10%, preferably 0.1 to 5%, based on the total weight of the periodontal therapeutic composition.

The antioxidant component may be a mixture of two kinds of antioxidant components mixed at a weight ratio of 1: 9 to 9: 1, respectively.

The antioxidant component may be an antioxidant component mixed at the same weight ratio when two mixed components are used.

When three or more kinds of antioxidant components are used, antioxidant components mixed at the same weight ratio can be used.

The sustained periodontal treatment composition for topical administration of the present invention may be formulated in the form of an ointment.

The sustained periodontal therapeutic composition for topical administration of the present invention may be an ointment base so as to be formulated in the form of an ointment.

In the above, the ointment base may be the rest of the antibiotic, the polyacrylic acid polymer, the water-soluble polymer, and the antioxidant component in the sustained periodontal treatment composition for topical administration.

In order to attain the object of the present invention, it is preferable to provide a sustained periodontal therapeutic composition for topical administration according to the above-mentioned conditions, when the sustained periodontal treatment composition for topical administration of the present invention is applied under various conditions.

Hereinafter, the present invention will be described in detail by way of Comparative Examples, Examples and Experimental Examples. However, these are for the purpose of illustrating the present invention in more detail, and the scope of the present invention is not limited thereto.

<Comparative Example>

2% by weight of minocycline hydrochloride and 98% by weight of plastibase were put into a mixing and mixing apparatus and mixed at 60 DEG C for 2 hours to prepare a treatment agent for periodontitis.

Example 1: Preparation of sustained periodontal treatment for topical administration

10% by weight of sodium CMC (sodium carboxymethyl cellulose), 0.5% by weight of sodium alginate, 0.5% by weight of hydroxypropylmethylcellulose 2910, 2% by weight of carboxymethylcellulose hydrochloride, and 2% by weight of minocycline hydrochloride, carbomer 940 and carbomer 971 in a weight ratio of 1: (HPMC 2910) (ShinEtsu, Japan), 1% by weight of hydroxypropyl cellulose (HPC) and 79.5% by weight of plastibase at 550 rpm for 2 hours at 550 rpm Respectively.

Table 1 below shows the compositions of the above-mentioned periodontal remedy.

&Lt; Examples 2 to 9 > Preparation of sustained periodontal remedy for local administration

The ingredients of the contents shown in the following Tables 1 and 2 were mixed at 60 rpm for 2 hours at 550 rpm to prepare a treatment agent for periodontal disease of Examples 2 to 9.

Table 1 and Table 2 below show the compositions of the agents for treating periodontal disease of Examples 2 to 9.

Composition (unit: wt%) of Examples 1 to 4 ingredient Example 1 Example 2 Example 3 Example 4 Antibiotic Minocycline hydrochloride 2 2 2 2 Polyacrylic acid polymer Cabomer 940+ Cabomer 971 2 2 2 2 2 water soluble
Polymer sodium CMC 10 10 10 6 Sodium alginate 0.5 0.5 0.5 One HPMC2910 0.5 10 15 5 HPC One One One 0.5 Dextrin - - - 2 Ointment mechanism Plastibase 79.5 74.5 6935 81.5 Sum 100 100 100 100

Composition (unit: wt%) of Examples 5 to 9 ingredient Example 5 Example 6 Example 7 Example 8 Example 9 Minocycline hydrochloride 2 2 2 2 20 Cabomer 940+ Cabomer 971 2 2 2 - - sodium CMC 6 6 10 10 6 Sodium alginate One One One 0.5 One HPMC 2910 10 15 0.5 0.5 15 HPC 0.5 0.5 0.5 0.5 0.5 Dextrin - - - 2 2 Plastibase 78.5 73.5 79.5 80 73.5 Sum 100 100 100 100 100

On the other hand, 0.5 g of the comparative example of the periodontitis therapeutic composition and the periodontitis treating composition of each of Examples 1 to 9 was applied to a grooved plastic plate. Then, water was continuously and constantly flown constantly to the periodontitis therapeutic composition of Comparative Example 1 and the periodontal treatment composition of Examples 1 to 9, and the presence or absence of the periodontal therapeutic composition remained after 3 hours.

In the case of the comparative example of the periodontitis therapeutic composition, almost no residual composition was observed. However, it was confirmed that the compositions of the periodontal healing agents of Examples 1 to 9 had a certain variation, but remained more than the comparative example of the periodontal treatment composition. Specifically, the remaining amount of the composition for treating periodontal disease of Example 3, Example 4 and Example 7 was observed to be large.

&Lt; Examples 10 to 18 > Preparation of sustained periodontal remedy for local administration

The components listed in Tables 3 to 4 were mixed at 60 rpm for 2 hours at 550 rpm to prepare a treatment agent for periodontitis of Examples 10 to 18.

Table 3 and Table 4 below show the compositions of the agents for treating periodontal disease of Examples 10 to 18.

Composition (units: wt%) of Examples 10 to 13 ingredient Example 10 Example 11 Example 12 Example 13 Antibiotic Minocycline hydrochloride 2 2 2 2 Polyacrylic acid polymer Carbomer 940 2 8 25 - Cabomer 971 - - - One Carbomer 940 + carbomer 971 (1: 1) - - - - receptivity
Polymer sodium CMC 10 10 10 10 Sodium alginate 0.5 0.5 0.5 0.5 HPMC2910 10 10 10 10 HPC 0.5 0.5 0.5 0.5 Ointment mechanism Plastibase 75 69 52 76 Sum 100 100 100 100

Composition (unit: wt%) of Examples 14 to 18 ingredient Example 14 Example 15 Example 16 Example 17 Example 18 Minocycline hydrochloride 2 2 2 2 2 Carbomer 940 - - - - Cabomer 971 8 25 - - - Carbomer 940+ carbomer 971 (1: 1) - - One 8 25 sodium CMC 10 10 10 10 10 Sodium alginate 0.5 0.5 0.5 0.5 0.5 HPMC2910 10 10 10 10 10 HPC 0.5 0.5 0.5 0.5 0.5 Plastibase 69 52 76 69 52 Sum 100 100 100 100 100

Experimental Example 1: Release of minocycline hydrochloride released from the periodontitis therapeutic agent

0.5 g each of the gingivitis therapeutic agent of the comparative example and the agent for treating periodontal disease of Examples 10 to 18 is put into the osmotic membrane, and then the vessel is filled with 50 mL of water. The container was placed in a shaking water bath maintained at 37 占 폚 and observed for 10 days.

After the osmotic membrane was removed, the test solution was filtered to measure the content of minocycline hydrochloride released from the therapeutic agent for periodontitis in each of Comparative Examples and Examples 10 to 18, Table 6 shows the results.

Comparative Example and Examples 10 to 13 Release of minocycline hydrochloride released from the periodontal remedy Item Comparative Example Example 10 Example 11 Example 12 Example 13 Emission of minocycline hydrochloride 17% 100% 100% 100% 95%

Examples 14 to 18 Release of minocycline hydrochloride released from the periodontal drug Item Example 14 Example 15 Example 16 Example 17 Example 18 Emission of minocycline hydrochloride 100% 89% 97% 100% 93%

&Lt; Experimental Example 2 >

0.5 g each of periosteal remedy prepared in Examples 11, 15 and 17 and comparative periosteal remedy prepared as in Example 17, and periorin (Japanstar, Sunstar) as a control agent were put into each osmotic pressure membrane, 20 mL. The container was placed in a shaking water bath maintained at 37 ° C and maintained at 15 rpm. The conditions were set considering the change caused by saliva and food intake after the periodontal treatment agent was injected into the periodontal pouch, and the release pattern of the drug from each treatment agent was confirmed under the above conditions.

The eluate was taken at intervals of 2 hours, 3.5 hours, 14 hours, 1 day, 2 days, 5 days, 6 days, 7 days, 10 days, 12 days and 15 days. The dissolution profile of the eluate was measured at 272 nm according to the UV-absorbance method, and the elution pattern of the drug was shown in Fig. 1, and the elution amount of the drug was shown in Fig.

In FIGS. 1 and 2, most of the cases of the periodontal disease treatment of comparative examples did not release the drug, and the periodontal disease treatment agent of Example 11 and the periodontal treatment agent of Example 17 normally performed drug release (see FIG. 1).

The comparative drug, the periodontitis treatment agent of Example 11, and the periodontitis treatment agent of Example 17 are similar in drug release pattern but slightly different in maximum release time. In the case of the control agent and the agent for treating periodontitis of Example 11, the maximum release is shown in 0-2 hours and 0-3.5 hours respectively, and in case of the periodontitis treatment agent of Example 17, the maximum release is observed in 1 day to 2 days. In the control drug and the treatment of periodontal disease of Example 11, most of the drug release was observed until day 2 with the maximum drug release in the early stage. In the case of the periodontitis treatment agent of Example 17, the drug release was gradually released in the early stage, And the drug release is gradually reduced (see FIG. 2).

As a result, the sustained-type periodontal treatment agent for topical administration as described above can provide a similar pattern to that of the control drug, or it can be a drug for periodontitis that can release drugs constantly during the treatment period, Can be achieved.

In particular, in the case of the periodontitis treatment agent of Example 15, the sustained-type periodontal treatment agent for local administration showing a longer drug release pattern than the one-week-old formulated agent by controlling the release rate, Since the drug is released for 3 weeks, a therapeutic effect can be expected for 2 to 3 weeks (see FIG. 1 and FIG. 2).

&Lt; Examples 19 to 22 > Preparation of sustained periodontal remedy for local administration

The ingredients of the ingredients listed in Table 7 below were mixed at 60 DEG C and 550 rpm for 2 hours, respectively, to prepare the agents for treating periodontal disease of Examples 19 to 22.

Table 7 shows the composition of the treatment agents for periodontal disease of Examples 19 to 22.

The compositions (units: wt%) of Examples 19 to 22, ingredient Example 19 Example 20 Example 21 Example 22 Antibiotic Minocycline hydrochloride 2 3 5 7 Polyacrylic acid polymer Carbomer 940 8 10 12 15 receptivity
Polymer sodium CMC 10 10 10 10 Sodium alginate 0.5 0.5 0.5 0.5 HPMC2910 10 10 10 10 HPC 0.5 0.5 0.5 0.5 Anti-oxidant
ingredient Tocopherol 0.06 0.06 - - Chitosan 0.2 - 0.06 - Vitamin C - 0.2 - 0.06 Sitosterol - - 0.2 0.2 Ointment mechanism Plastibase 68.74 65.74 61.74 56.74 Sum 100 100 100 100

&Lt; Experimental Example 3 >

The periodontitis treatment agent of Example 11 and the periodontitis treatment agent of Example 19 were simultaneously stored at a temperature of 40 ± 2 ° C. and a humidity of 75 ± 5% for 6 months in a stability tester and observed. The results are shown in FIG.

In the photograph of FIG. 3, the first one and the second one indicate that the periodontitis treatment agent of Example 11 was stored at a temperature of 40 ± 2 ° C. and a humidity of 75 ± 5% for 6 months. In the photograph of FIG. 3, And the fourth shows that the periodontitis treatment agent of Example 19 was stored at a temperature of 40 ± 2 ° C. and a humidity of 75 ± 5% for 6 months.

As shown in FIG. 3, a slight browning phenomenon occurred in the agent for treating periodontitis in Example 11, but no browning was observed in the agent for treating periodontitis in Example 19.

These results suggest that the antioxidants of tocopherol and chitosan did not cause browning due to the improved stability of the periodontitis treatment agent.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention as defined in the appended claims. It will be understood that the invention may be variously modified and changed.

The therapeutic composition for periodontitis including the antibiotic, polyacrylic acid polymer, water-soluble polymer, antioxidant component and ointment base of the present invention can be administered locally at the site where periodontitis occurs and the therapeutic composition applied to the site where periodontitis occurs is decomposed with time And can be treated by administering it to a site requiring long-term continuous periodontitis.

In addition, the composition for treating periodontal disease according to the present invention is a composition for treating periodontal disease in which the composition for treating periodontal disease is completely decomposed at the end of treatment with antibiotics, It is possible to provide an antimicrobial composition for the treatment of persistent periodontitis, which is industrially applicable.

Claims (7)

A sustained periodontal therapeutic composition for topical administration, which comprises an antibiotic, a polyacrylic acid polymer, a water-soluble polymer, an antioxidant component and an ointment base,
The antibiotic is minocycline,
The polyacrylic acid polymer is a carbomer 971, comprising 25% by weight based on the total weight of the composition,
The water-soluble polymer is at least one selected from the group consisting of sodium carboxymethyl cellulose, sodium alginate, hydroxypropylmethyl cellulose, and hydroxypropyl cellulose,
Wherein the antioxidant component is at least one selected from the group consisting of chitosan, vitamin C, tocopherol and an extract containing a sitosterol,
The ointment base is a plastibase,
Wherein the formulation of the composition is an ointment. The method according to claim 1,
Wherein the composition comprises 2 to 50% by weight of antibiotics, 25% by weight of a polyacrylic acid polymer, 2 to 50% by weight of a water-soluble polymer, 0.04 to 10% by weight of an antioxidant component and the balance ointment base. The method according to claim 1,
Wherein the antibiotic is contained in a polyacrylic acid polymer in an amount of 10 to 50% by weight based on the weight of the polyacrylic acid polymer. delete delete delete delete

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