KR20170065944A - Oral composition comprising non aqueous anti-inflammatory component and amino acid surfactant - Google Patents

Abstract

The present invention relates to oral compositions, and more particularly to oral compositions that enhance the efficacy of non-aqueous anti-inflammatory ingredients. The oral composition comprising the non-aqueous anti-inflammatory component according to the present invention as an active ingredient, wherein the oral composition further comprises an amino acid surfactant to improve the efficacy of the non-aqueous anti-inflammatory component, Or exert an excellent effect on the treatment.

Description

[0001] The present invention relates to an oral composition comprising an anti-inflammatory component and an amino acid surfactant,

The present invention relates to oral compositions, and more particularly to oral compositions that enhance the efficacy of non-aqueous anti-inflammatory ingredients.

Periodontal tissue consists of alveolar bone, gingiva (gums) and periodontal ligament. The gingiva is a part of the tooth supporting tissue that we can see inside the oral cavity. The disease (gingivitis) starts here. When the disease deepens and spreads deeper into the supporting tissue, the periodontal ligament The ligaments are destroyed and the alveolar bone surrounding the teeth is destroyed, resulting in periodontitis.

Gum disease (periodontal disease), including gingivitis and periodontal disease, is an inflammatory state of the tooth supporting tissues caused by bacteria, and ultimately causes loss of teeth due to bleeding, formation of the periodontal pouch and destruction of the alveolar bone. These gum disease progresses to bacterial colony formation, bacterial infiltration of periodontal tissue, and destruction of periodontal tissue. Specifically, due to poor oral hygiene conditions, oral bacteria form biofilms, resulting in inflammation and bleeding from the gums and bad breath, and deeper gingival crevices between the teeth and gums The periodontal pouch causes periodontal disease, which causes periodontal disease. As periodontitis progresses, mild irritation, such as brushing, may cause bleeding from the gums and swelling, often causing acute inflammation and pain. Such inflammation lowers the function of making bone and increases the action of absorbing bone, resulting in lowering and destruction of alveolar bone, resulting in loss of teeth.

On the other hand, Centella asiatica extract, Lilium extract, tocopheryl acetate, allantoin, ursodeoxycholic acid (UDCA) as a antiinflammatory material for preventing inflammation of the gums in the oral composition, And the like have been used. In this case, the water-insoluble anti-inflammatory component is present in a dispersed suspension form in the formulation, which is ineffective to transfer into the gingival fissure to which the anti-inflammatory component should act and has a limited effective contact.

Accordingly, the present inventors have conducted studies to improve the effectiveness of the non-water-soluble anti-inflammatory component by increasing the effective contact within the gingival fissure.

Korean Patent Publication No. 10-2008-0063898

DISCLOSURE OF THE INVENTION Accordingly, it is an object of the present invention to solve the above-mentioned problems of the prior art, and it is an object of the present invention to provide an anti- And to provide a preventive and / or therapeutic effect of excellent oral inflammation.

In order to solve the above problems, the present invention provides an oral composition comprising a non-aqueous anti-inflammatory component as an active ingredient, wherein the composition further comprises an amino acid surfactant to improve the efficacy of the non- Or a pharmaceutically acceptable salt thereof.

The present inventors have found that in order to prevent and / or treat inflammation in the oral cavity, the present inventors have found that a non-aqueous anti-inflammatory component such as Centella asiatica extract, Zucchini extract, tocopheryl acetate, allantoin, Ursodeoxycholic acid and the like were used. However, in order to overcome the fact that these components are present in the form of a dispersed suspension in a formulation, it is difficult to exert an effective effect. When an amino acid surfactant is included together, The present inventors have surprisingly found that the amino acid-based surfactant is micellized in the formulation to have hydrophilic properties and is dissolved in saliva to improve penetration into the gingival sulcus.

As used herein, the term "inflammation in the mouth" comprehensively refers to inflammation that may occur in the oral tissues, wherein the oral tissues are part of the function of digesting the food ingested as part of the digestive system functionally It may include tissue, hard tissue, teeth, alveolar bone, and cementum as hard tissues, and soft tissues such as gingiva, buccal mucosa, study dogs, tongue, and the like.

In particular, the oral composition according to the present invention is characterized in that the water-insoluble anti-inflammatory component is easy to penetrate into the gingival sulcus, which is difficult to penetrate conventionally, and exhibits excellent effects on inflammation occurring between the gum and the tooth. It has been very difficult to effectively penetrate an effective ingredient into a narrow gap such as a gingival fissure and effectively apply to an inflammation site, but the oral composition according to the present invention solves this problem at the source.

As used herein, the term "prophylactic " means any act that inhibits or delays oral inflammation using the oral composition. Also, as used herein, the term "treatment" refers to any action that alleviates or cures oral inflammation using the oral composition.

As used herein, the term "non-aqueous anti-inflammatory component" includes all non-aqueous materials having anti-inflammatory properties. The term "non-aqueous" It is also a comprehensive term that includes.

The water-insoluble anti-inflammatory component may be, for example, but not limited to, Centella asiatica extract, Capsicum extract, tocopheryl acetate, allantoin, ursodeoxycholic acid, .

Therefore, the non-aqueous anti-inflammatory component contained in the oral composition according to the present invention as an active ingredient is selected from the group consisting of Centella asiatica extract, Zucchini extract, tocopheryl acetate, allantoin and ursodeoxycholic acid ursodeoxycholic acid), preferably Centella asiatica extract, Liliaceae extract, or tocopheryl acetate.

Particularly, the present inventors confirmed that when the oral composition according to the present invention contains Centella asiatica extract, L. extract or tocopheryl acetate as an active ingredient, the efficacy of the above-mentioned non-water-soluble anti-inflammatory ingredients can be maximized. The Centella asiatica extract and succulent extract are components derived from plants, which are natural ingredients not subjected to chemical processes except extraction, and also have an effect of stimulating collagen production, and as an inflammation-preventing ingredient acting on the oral cavity without stimulation, And the effect can be maximized. The tocopheryl acetate has been used for a long time in the human body, and its effect can be maximized without side effects.

"Centella asiatica extract" used in the present invention refers to an extract obtained by the extraction treatment of Centella asiatica, a diluted solution or a concentrate of the extract, a dried product obtained by drying the extract, a preparation or a purified product of the extract, And mixtures thereof, extracts of all the formulations which can be formed using the extract itself and the extract.

The Centella asiatica extract of the present invention can be extracted from various organs of natural, hybrid, or variant plants of the Centella asiatica, for example, seeds of Centella asiatica, roots, , Leaves, flowers, trunk of fruit, bark of fruit as well as plant tissue culture.

The Centella asiatica extract of the present invention may be dried leaves of Centella asiatica, preferably Centella asiatica.

More particularly, the leaf of Centella asiatica is cut into a water of about 1 to 20 times, preferably about 5 to 15 times as much as the centella asiatica leaf weight (kg) as a solvent, water having a carbon number of 1 to 4 Lower alcohols or a mixed solvent thereof may be used, and more preferably 70 to 99% (v / v) ethanol may be used.

It is also possible to heat at a temperature not lower than room temperature for not less than 2 hours, preferably not lower than 50 ° C for not less than 1 hour, stirring for about 2 to 12 hours, ultrasonic extraction or reflux cooling extraction, The extract can be obtained by filtration, concentration under reduced pressure or drying.

In addition, it can be extracted by a supercritical extraction method according to a known method, and various methods known in the art can be combined with extraction of a natural product.

In the present invention, the backbone extract may be extracted from various organs or parts of the backbag, and may be obtained by extracting, for example, leaves, flowers, fruits, stem, roots, branches, Can be obtained by extracting the shell.

The backbone extracts may include all extracts obtained by conventional extraction methods known in the art, such as organic solvent extract, water extract extracted with water, supercritical extract, and the like. Preferably an extract obtained by extracting with water, an organic solvent or a mixture thereof. The organic solvent may be an organic solvent known in the art without limitation, preferably a lower alcohol such as methanol, ethanol, isopropyl alcohol, and butanol; Polyhydric alcohols such as glycerol, ethylene glycol, propylene glycol and 1,3-butylene glycol; And hydrocarbon solvents such as petroleum ether, methyl acetate, ethyl acetate, benzene, hexane, methylene chloride, diethyl ether, dichloromethane and chloroform, or mixtures thereof.

The crude extract can be used as it is in a liquid state by extraction solvent, diluted in CO ₂ supercritical extraction or in a solvent, or can be used in powder form. The pulverization may be carried out by conventional methods known in the art, such as vacuum drying, freeze drying, and denominator drying.

The extract of the present invention includes not only the above-mentioned extraction solvent, but also an extract obtained by a conventional purification process. Specifically, the extract of the present invention can be purified by an extraction solvent purification process, for example, a membrane separation using a filtration membrane having a cut-off value at a certain molecular weight, various chromatography for separation according to size, charge, hydrophobicity or affinity And a purification process such as separation by the above-mentioned method may be additionally carried out.

In the present invention, the tocopheryl acetate is a substance represented by the following structural formula (1). The chemical formula of tocopheryl acetate is C ₃₁ H ₅₂ O ₃ , and its molecular weight is 472.74. The tocopheryl acetate that can be used in the present invention includes all of tocopherol acetate, artificially synthesized tocopherol acetate and commercially available tocopherol acetate which are separated from plants containing tocopheryl acetate.

[Chemical Formula 1]

In the present invention, the water-insoluble anti-inflammatory component may be contained in an amount of 0.001 to 5% by weight based on the total weight of the composition. If the amount of the water-insoluble anti-inflammatory component is less than 0.001% by weight based on the total weight of the composition, the effective effect on oral inflammation such as gingivitis and periodontitis may not be exhibited. If the content is more than 5% by weight, It can be uneconomical.

As used herein, the term "amino acid surfactant" is a generic term for an amino acid-containing surfactant.

Thus, the amino acid surfactant that is included as an active ingredient in the oral composition according to the present invention is sodium lauroyl glutamate, sodium myristoyl glutamate, sodium cocoyl glutamate, sodium lauroyl sarcosinate, sodium cocoyl taurate, potassium Cocoyl glycinate, sodium cocoyl glycinate, sodium stearoyl glutamate, sodium lauroyl aspartate, potassium lauroyl glutamate, potassium myristoyl glutamate and the like, preferably sodium lauroyl glutamate, At least one selected from the group consisting of glutamate, sodium myristoyl glutamate, sodium cocoyl glutamate, sodium lauroyl sarcosinate, sodium cocoyl taurate, potassium cocoyl glycinate and sodium cocoyl glycinate.

In the present invention, the amino acid surfactant may be contained in an amount of 0.001 to 5% by weight based on the total weight of the composition. When the amount of the amino acid surfactant is less than 0.001% by weight based on the total weight of the composition, it may fail to form an effective effect due to the non-water-soluble anti-inflammatory component and micelle formation. If the amount is less than 5% by weight, The quality may be deteriorated.

Also, in order to form micelles in the present invention, the weight ratio of the non-water-soluble anti-inflammatory component and the amino acid surfactant is also important. The weight ratio of the water-insoluble anti-inflammatory component and the amino acid surfactant may be 1:10 to 1000, preferably 1:30 to 500, and more preferably 1:40 to 200. If the ratio is out of the above range, micelle formation may not be properly performed.

The oral composition according to the present invention is characterized in that the non-water-soluble anti-inflammatory component and the amino acid surfactant form micelles, and the non-aqueous anti-inflammatory component penetrates into the gingival fissure, that is, between the teeth and the gum, Thereby improving the efficacy of the non-aqueous anti-inflammatory component.

The oral composition according to the present invention may be formulated as a wetting agent, an abrasive, a pharmacological agent, a sweetening agent, a pH adjusting agent, an antiseptic, a binder, a fragrance or a purified water for the purpose of proper formulation and formulation stability, , And the like, but the present invention is not limited thereto.

The wetting agent may be, for example, but not limited to, concentrated glycerin, glycerin, sorbitol, amorphous sorbitol, polyethylene glycols or propylene glycol. The amount of the wetting agent may be 1 to 70 wt% %, But is not limited thereto.

The abrasive may include, but is not limited to, precipitated silica, silica gel, zirconium silicate, kaolin, calcium monohydrogenphosphate, anhydrous calcium hydrogen phosphate, hydrated alumina, light calcium carbonate, Metaphosphate or aluminum silicate may be used. The amount of such abrasive to be used may generally be 1 to 60% by weight based on the total weight of the oral composition, but is not limited thereto.

The pharmaceutical agent may be, for example, but not limited to, sodium fluoride, sodium fluorophosphate, sodium fluoride, tin fluoride, chlorohexidine, allantoin chlorohydroxy aluminate, aminocaproic acid, zinc chloride, pyridoxine hydrochloride, Tocopherol acetate, enzymes and the like, or a mixture of two or more thereof.

The sweetening agent may be, for example, but not limited to, sodium saccharin, xylitol, erythritol, sucralose, maltitol, aspartame or stevioside. The amount of the sweetener to be used is generally 0.05 to 2 wt. %, But is not limited thereto.

Examples of the pH adjuster include, but are not limited to, sodium phosphate, disodium phosphate, citric acid, or triethanolamine.

Examples of the preservative include, but are not limited to, benzoic acid, methylparaben, propylparaben or sodium benzoate.

Examples of the binder include, but are not limited to, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, guar gum, pectin, polyvinylpyrrolidone, carboxyvinyl polymer, alginic acid Sodium, laponite, carbomer, carrageenan, xanthan gum or alginate, and the like, preferably sodium carboxymethylcellulose. The amount of such a binder to be used is generally 0.1 to 3% by weight, preferably 0.5 to 2% by weight based on the total weight of the oral composition, but is not limited thereto.

Examples of the fragrance include, but are not limited to, peppermint oil, spearmint oil, menthol, etc., alone or in combination.

The oral composition of the present invention may also contain enzymes such as dextrinase as other additives.

The oral composition of the present invention may contain, in addition to the active ingredient, the additive, a residual amount of water, preferably purified water.

The oral composition according to the present invention may have formulations such as, for example, dentifrices, mouthwashes, sprays, mouthwashes, mouthwashes, tooth whitening agents, and the like, And may be formulated by conventional means known to those of ordinary skill in the art.

The oral composition comprising the non-aqueous anti-inflammatory component according to the present invention as an active ingredient, wherein the oral composition further comprises an amino acid surfactant to improve the efficacy of the non-aqueous anti-inflammatory component, Or exert an excellent effect on the treatment.

Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples. However, the embodiments and experimental examples according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the above-described embodiments and experiments. The embodiments and experimental examples of the present invention are provided to enable those skilled in the art to more fully understand the present invention.

Material preparation

Centella Asia Tikka  Extract preparation

In order to produce Centella asiatica extract, we added 1000 g of 95% (v / v) ethanol as an extracting solvent to 100 g of Centella asiatica (cognis), which was dried and pulverized, for 4 hours, at 60 ° C , And 2 g of Centella asiatica extract was obtained.

Preparation of extract

The present inventors used a dried extract after pulverization and subjected to CO ₂ supercritical extraction at a temperature of 30 to 60 ° C and a pressure of 10 to 30 mpa, followed by vacuum drying and using the extract.

Tocopherol acetate

The tocopherol acetate used in the present invention was a raw material which conformed to the Korean Pharmacopoeia (KP) standard.

Manufacturing example

The inventors of the present invention manufactured the detergent compositions of Examples 1 to 4 and Comparative Examples in accordance with the general detergent (dentifrice) composition manufacturing method at the components and composition ratios shown in Table 1 below.

(Unit: wt%) Comparative Example 1 Comparative Example 2 Comparative Example 3 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Precipitated silica 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00 Sodium fluoride 0.22 0.22 0.22 0.22 0.22 0.22 0.22 0.22 0.22 0.22 0.22 Carboxymethylcellulose sodium 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Sorbitol 50.00 50.00 50.00 50.00 50.00 50.00 50.00 50.00 50.00 50.00 50.00 Sodium saccharin 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 0.10 Spices 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Centella asiatica extract 0.01 - - 0.01 0.01 0.01 0.01 - - - - Tocopherol acetate - 0.05 - - - - - 0.05 0.05 - - Acacia extract - - 0.05 - - - - - - 0.05 0.05 Sodium lauryl sulfate - - - 2.00 - - - 2.00 - 2.00 - Sodium myristoyl glutamate - - - - 2.00 - - - 2.00 - 2.00 Sodium cocoyl glutamate - - - - - 2.00 - - - - - Sodium lauroyl glutamate - - - - - - 2.00 - - - - Purified water Balance
(To 100) Balance
(To 100) Balance
(To 100) Balance
(To 100) Balance
(To 100) Balance
(To 100) Balance
(To 100) Balance
(To 100) Balance
(To 100) Balance
(To 100) Balance
(To 100)

Experimental Example  1: Oral composition Residual force  Measure

The inventors of the present invention measured the residual force for confirming the effect of enhancing the penetration ability of gingival fissure of the oral composition according to the present invention. The ratio of the dentifrice composition having the same composition as that of Examples 1 to 8 and Comparative Examples 1 to 3 and saliva was 1: Two toothpaste slurries were prepared.

100 mu L was applied to oral mucosa extracted from a Golden Syrian hamster having a weight of 70 to 90 g, dried at room temperature for 1 hour, and washed with about 10 mL of water. The washed specimen was eluted with 2 to 10 ml of ethanol having a purity of 95% or more, which is a solvent capable of dissolving Centella asiatica extract and tocopherol acetate, such as ethanol. After the active ingredient was eluted, ≪ / RTI > high resolution liquid chromatography (HPLC) analysis equipment.

The results were obtained by calculating the residual ratio as a percentage of the initial amount of the adsorbent, and calculating the obtained results using the following equation: < EMI ID = 1.0 > Table 2 shows the results.

Comparative Example 1 Comparative Example 2 Comparative Example 3 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Residual rate
(%) 2.8 2.1 2.6 7.1 23.6 21.5 21.9 5.2 21.9 6.0 22.1

As a result, Comparative Example 1, Comparative Example 2, Comparative Example 3, Example 1, Example 2, Example 3, Example 4, Example 5, Example 6, Example 7, In Example 8, the residual rates were 2.8%, 2.1%, 2.6%, 7.1%, 23.6%, 21.5%, 21.9%, 5.2%, 21.9%, 6.0% and 22.1% . In particular, it was confirmed that the residual ratio was high in Examples 2, 3, 4, 6 and 8 using an amino acid surfactant.

That is, it was confirmed that the composition according to the present invention has an enhanced gingival penetration ability.

Experimental Example  2 :  gingivitis  Confirming changes in the index

The present inventors confirmed the change in the gingivitis index of the subject after using the detergent composition prepared in the composition of Table 1 for 3 months on a group basis.

Test Methods

1) The subjects were selected for 20 ~ 45 year - old adults who did not have systemic specific symptoms, no oral restorations, and did not have periodontal disease.

2) The subjects were randomly divided into 30 subjects in each of the examples and the comparative examples. Correct toothbrushing methods were trained and oral examinations were conducted. The gingival index (Gingival Bleeding Index, Loe & Silency Index) was measured based on the studies described in the literature Journal of Oral Health, Vol. 22, No. 1, p. 27).

3) Scaling was performed on all teeth in the test group.

4) Comparative Example The oral dentifrice was used as a control toothpaste for 14 days, and the oral gingivitis index was used as the initial value.

5) The dentifrice of the example and the toothpaste of the comparative example were distributed to each subject, and brushing was carried out three times a day for three months in the same manner as usual, and oral examination was performed at one month, two months and three months, and the gingival index was scored.

6) The test results were compared with the initial one month, two months, and three months after using the test group, and the test results were tested by t-test.

As a result, Comparative Examples 1, 2, 3, 1, 2, 3, 4, 5, 6, 7, In Example 8, the initial gingival index was 6.83%, 8.33%, 0.90%, 19.84%, 31.49%, 32.53%, 31.40%, 12.80%, 23.84%, 16.03%, and 30.70% In the examples, statistically significant effects were obtained, and in particular, in Examples 2, 3, 4, 6 and 8 using the amino acid surfactant, it was confirmed that the gingivitis reduction effect was large.

N m ± s.d. Early After 1 month Two months later Three months later △ (%) Comparative Example 1 20 1.17 ± 0.31 1.14 0.32 1.10 + - 0.34 1.09 ± 0.31 0.08 (6.83%) Comparative Example 2 20 1.20 0.46 1.11 + - 0.41 1.15 + 0.33 1.10 0.29 0.10 (8.33%) Comparative Example 3 20 1.11 + - 0.32 1.17 + - 0.33 1.11 ± 0.29 1.10 0.31 0.01 (0.90%) Example 1 20 1.31 + - 0.38 1.28 + - 0.33 1.15 ± 0.26 1.05 + 0.21 0.26 (19.84%) Example 2 20 1.27 + - 0.42 1.04 + - 0.93 1.09 + - 0.38 0.87 ± 0.32 0.40 (31.49%) Example 3 20 1.26 + - 0.38 1.18 0.31 1.01 + - 0.36 0.85 ± 0.22 0.41 (32.53%) Example 4 20 1.21 0.33 1.01 + - 0.45 1.05 + - 0.32 0.83 0.31 0.38 (31.40%) Example 5 20 1.25 0.41 1.22 ± 0.36 1.09 + - 0.38 1.09 + - 0.42 0.16 (12.80%) Example 6 20 1.30 0.36 1.21 0.61 1.09 ± 0.48 0.99 ± 0.40 0.31 (23.84%) Example 7 20 1.31 0.26 1.14 ± 0.88 1.16 ± 0.38 1.10 0.26 0.21 (16.03%) Example 8 20 1.27 ± 0.21 1.03 + - 0.63 1.02 + - 0.38 0.88 0.33 0.39 (30.70%)

Claims (7)

An oral composition comprising a non-aqueous anti-inflammatory component as an active ingredient, wherein the composition further comprises an amino acid-based surfactant to improve the efficacy of the non-aqueous anti-inflammatory component. The method according to claim 1,
The water-insoluble antiinflammatory component is at least one selected from the group consisting of Centella asiatica extract, Capsicum extract, tocopheryl acetate, allantoin, and ursodeoxycholic acid. Or a pharmaceutically acceptable salt thereof, for the prophylaxis or treatment of inflammation in the mouth. The method according to claim 1,
The amino acid surfactant may be at least one selected from the group consisting of sodium lauroyl glutamate, sodium myristoyl glutamate, sodium cocoyl glutamate, sodium lauroyl sarcosinate, sodium cocoyl taurate, potassium cocoyl glycinate and sodium cocoyl glycinate Wherein the oral composition is at least one selected from the group consisting of oral, The method according to claim 1,
Wherein the water-insoluble anti-inflammatory component is contained in an amount of 0.001 to 5 wt% based on the total weight of the composition. The method according to claim 1,
Wherein the amino acid surfactant is contained in an amount of 0.001 to 5 wt% based on the total weight of the composition. The method according to claim 1,
Wherein the weight ratio of the water-insoluble anti-inflammatory component and the amino acid surfactant is 1: 10-1000. The method according to claim 1,
Wherein the water-insoluble anti-inflammatory component and the amino acid-based surfactant form a micelle in the composition.