JPS61225115A - Double capsule and oral composition containing said capsule - Google Patents

Abstract

PURPOSE:To produce a double capsule having improved long-term stability of a water-soluble drug such as vitamins, crude drugs, etc., liable to be influenced with the coexisting components in a composition for oral application, by using the water-soluble drug as a core, and coating the core successively with an oleophilic substance and a hydrophilic substance. CONSTITUTION:A water-soluble drug selected from vitamins and crude drugs or their extracts, especially ascorbic acid having high safety and effective for the removal of stain is compounded to a composition for oral application. In the above process, the agent is used as a core, and the core is coated first with an oleophilic substance (especially a waxy substance) and then with a hydrophilic substance (especially gelatin) to obtain a double capsule. The degradation and oxidation of the drug by surfactants, perfumes, metals, etc., existing in the system can be prevented and the drug-action can be maintained stably for a long period during storage. The capsule can be collapsed easily in use to release the drug into the system to exhibit the drug action in high efficiency.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention provides a capsule in which a water-soluble drug that is unstable in a system is encapsulated in a double capsule to stabilize it, and a toothpaste containing the capsule. The present invention relates to an oral composition.

[Conventional technology]

BACKGROUND ART Various toothpastes containing various vitamins, herbal medicines, and their extracts have been developed to appeal to their medicinal effects. However, these drugs do not contain surfactants, which are present in toothpaste.
The problem is that it is easily affected by fragrances, metals, etc., and its medicinal efficacy decreases during storage, making it less effective when used. That is, it is considered difficult to stably incorporate these drugs into the above-mentioned system for a long period of time. In particular, it is said that ascorbic acid, a form of vitamin C, is effective in preventing gingivitis and eliminating bad breath when added to toothpaste. Method for derivatizing acids (JP-A-59-27810),
Stabilization methods have been proposed, such as adding stabilizers such as copper chlorophylls (Japanese Patent Publication No. 47-10399) and chelating agents, and encapsulation (Japanese Patent Publication No. 50-25011). However, when ascorbic acid is made into a stable derivative, the original effects of ascorbic acid are reduced, and it is difficult to obtain long-term stability in tooth brushing by adding various stabilizers. Furthermore, the above-mentioned encapsulation uses fine granular capsules in which fine particles containing a solid powder of a water-soluble medicinal agent such as ascorbic acid are coated with a wax-like substance, but sufficient stabilization has not been achieved yet. do not have.

[Problem that the invention seeks to solve]

Therefore, an object of the present invention is to provide a capsule capable of stably retaining a water-soluble drug that is susceptible to expiration due to coexisting substances for a long period of time, and an oral composition containing the capsule.

[Failure to solve the problem]

According to the present invention, storage stability can be greatly improved by forming a water-soluble drug that is easily affected by coexisting substances in an oral composition into a solution state and encapsulating this in a double capsule having a specific layer structure. The present inventors have discovered that ascorbic acid has an excellent stain-removing effect, that it is quickly released from the capsule during use and exhibits excellent medicinal efficacy, and that ascorbic acid in particular has an excellent stain-removing effect.

That is, the present invention provides a double capsule with a structure in which a water-soluble drug selected from the group of vitamins, herbal medicines and extracts thereof is used as a core agent, this is coated with a lipophilic substance, and these are further coated with a hydrophilic substance. An oral composition containing the capsule is provided.

The particle size of the double capsule used in the present invention is not particularly limited, but it is usually 10 to 5,000 from the viewpoint of ease of breaking the capsule.
μm1 is preferably 100-1000 μm. The water-soluble drugs that form the core of the capsule include vitamins,
At least one water-soluble drug selected from crude drugs and extracts thereof is used. Specifically, various herbal medicine ingredients such as vitamin B, vitamin C (ascorbic acid), bellflower, licorice, yellow oak, and shakola are exemplified. Among these, it is preferable to use ascorbic acid because it effectively removes stain. These water-soluble drugs are not powders,
Used in solution form. For example, 5 to 90% by weight (hereinafter,
%), preferably at a concentration of 10 to 50%. At this time, water or polyhydric alcohols such as glycerin and sorbitol are used as the solvent. When using water, it is desirable to use water from which oxygen has been removed to prevent oxidation due to dissolved oxygen. Further, when using a polyhydric alcohol, if the water-soluble drug is not dissolved, it is preferable to use it in a dispersed form. In the present invention, the water-soluble drug is not kept as a powder, but
Since it is used in the form of a solution, when the capsule is ruptured, the drug is quickly released into the system and acts on the oral cavity during a short period of time, such as when brushing teeth, and exerts excellent effects.

The inner layer agent of the capsule, that is, the substance used to coat the core agent, is a lipophilic substance with a melting point of 50.
Wax-like substances above ℃, specifically hydrocarbons such as paraffin wax and microcrystalline wax, waxes such as beeswax, carnano wax, and privet wax, stearic acid, noclumitic acid, lehenic acid, cerotic acid, etc. Examples include higher fatty acids, higher alcohols such as stearyl alcohol and ferryl alcohol, and thermoplastic substances such as polyethylene, vinyl chloride, and polystyrene.

Further, the outer layer agent of the capsule, that is, the substance for coating the outer side of the inner layer agent, is a hydrophilic substance, and specific examples thereof include gelatin, sodium carboxymethyl cellulose, gum arabic, and the like. The present invention is particularly characterized by using a lipophilic substance in the inner layer and a hydrophilic substance in the outer layer, whereby the drug in the core agent is protected from the surfactant by the lipophilic film and protected by the hydrophilic film. This protects it from fragrances, which are oil-based ingredients. Therefore, various combinations of lipophilic components and hydrophilic components can be made as desired;
It is preferable to use paraffin as the inner layer agent and gelatin as the outer layer agent because oxygen permeation can also be suppressed. In this case, after forming the capsule, it is more effective to harden the protein in the outer layer with an aldehyde such as glutaraldehyde or formalin, or an inorganic substance such as alum.

The double capsule of the present invention can be easily manufactured, for example, by the method shown below. It is produced by first covering a solution containing a water-soluble drug such as ascorbic acid with a lipophilic film by a melt-dispersion cooling method, and then depositing a hydrophilic film on the lipophilic film by phase separation. If desired, protein hardening agents as described above can then be added to toughen the capsules.

The double capsule of the present invention essentially has the structure described in 1. The amount of the core agent, the thickness of the inner layer, the outer layer, etc. can be adjusted arbitrarily, but the double capsule containing the water-soluble drug as the core agent solution 10
~90%, inner layer 5~40%, outer layer 5~50%, more preferably 40~60%, 15~20%, 25~
A good value is 40%.

In the present invention, the above-mentioned double capsules can be used in various toothpastes,
It can be blended into mouthwashes, gum surgers, chewing gums, etc. At this time, the amount of the above-mentioned double capsule in the oral composition is not particularly limited, but is preferably 1 to 5.
Add 0%. As other components of the oral composition of the present invention, commonly used components can be blended depending on the type thereof. For example, in the case of a dentifrice composition, the following components can be blended.

Abrasive aluminum oxide compound, dibasic calcium phosphate dihydrate and anhydride, silicic anhydride, aluminosilicate, calcium carbonate, calcium pyrophosphate, aluminum silicate, inert sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, One or more of calcium sulfate, synthetic resin, etc. can be blended in an amount of usually 20 to 90% of the total amount, particularly 20 to 60% in the case of toothpaste.

Binder carrageenan, carboxymethyl cellulose sodium,
One or more of sodium alginate, gum neck, polyvinyl alcohol, vegum etc. is usually 0.3 to 5
% blend.

Thickener sorbitol, glycerin, propylene glycol, 1.
One or more of 3-butylene glycol, polyethylene glycol, xylit, marnat, and lafutite are usually blended in an amount of 10 to 70%.

Surfactants Sodium lauryl sulfate, lauroyl sarcosinate, α-olefin sulfonate, taurate, lauryl monoglyceride sulfate, lauryl monoglyceride sulfonate, anionic active agents such as stone, lauric acid diechnolamide, stearyl monoglyceride, sucrose fatty acid ester , lactose fatty acid ester, lactitol fatty acid ester, maltitol fatty acid ester, nonionic surfactants such as polyoxyethylene sorbicun monostearate, and one or more surfactants such as amphoteric surfactants such as betaine type and amino acid type. is usually blended in an amount of 0.5 to 7%.

Others include saccharin sodium, stevioside, neohesveridine dihydrochalcone, thaumatin, clityrrhizin,
Sweeteners such as perilartine, preservatives such as parabens, various fragrances such as terpene compounds such as menthol and carvone, gelatin, peptone, etc. can be added. Furthermore, enzymes such as dextranase, amylase, protease, mutanase, lysozyme, and Lytec enzyme, alkali metal monofluorophosphates such as sodium monofluorophosphate, fluorides such as sodium fluoride, and stannous fluoride; compounds, chlorhexidine salts,
One or more drugs such as epsilon aminocaproic acid, tranexamic acid, aluminum chlorohydroxylalantoin, dihydrocholesterol, glycyrrhizin salts, sodium chloride, and water-soluble inorganic phosphoric acid compounds can be blended.

A dentifrice composition is produced by kneading the ingredients in item 1 with an appropriate amount of water, and the above-mentioned double capsule can be added during or after production. In addition, the toothpaste composition obtained in this way can be made into an aluminum tube, a laminate tube in which both sides of aluminum foil are laminated unevenly with plastic, etc.
It is stored in a predetermined container such as a plastic tube, a bottle-shaped container, an air-sol container, and the like for use.

Other oral compositions can also be produced using commonly used base materials and according to conventional methods.

〔Effect of the invention〕

According to the present invention, vitamins, herbal medicines, and their extracts are covered and protected by lipophilic substances and hydrophilic substances, so that surfactants, oily fragrance ingredients, and trace amounts of fragrance ingredients present in the system can be protected. It is neither altered by heavy metals nor promoted by oxidation, and is stably retained in oral compositions for long periods of time. In addition, the double capsule of the present invention is easily destroyed during use and releases the above-mentioned drug content into the system, but at this time, since the above-mentioned drug is in the form of a solution, it can quickly enter the oral cavity. can act on

Therefore, even when brushing teeth for a short period of time, the inherent medicinal effects of the drug can be efficiently exerted.

Furthermore, in addition to the above-mentioned effects, it has been found that when the water-soluble drug is ascorbic acid, stain (a general term for colored pellicle, plaque, tartar, etc. that adheres to the periphery of teeth) can be effectively removed. In other words, aromatic alcohols, which have traditionally been thought to be effective in removing stains, have safety issues, and metal chelating agents also chelate calcium, a component of teeth, which can lead to tooth loss. Although there was a risk of ash, the ascorbic acid-containing double capsule of the present invention is extremely safe and provides excellent effects.

Next, the present invention will be explained with reference to Examples, but the present invention is not limited thereto.

〔Example〕

Example 1 A double capsule containing water-soluble ascorbic acid was blended into a dentifrice composition, and the stability of ascorbic acid was investigated. 2
The method for producing heavy capsules and the toothpaste composition are shown below.

02 Method for producing double capsules Ascorbic acid solution (a degree 40%) was poured into melted paraffin and stirred to prepare a W/○ emulsion. At this time, the droplet diameter of the ascorbic acid solution was
~1000μ, the temperature of the system is 1~5 below the melting point of paraffin.
℃ higher temperature. Gradually add this W/O emulsion to water at the same temperature as this system with moderate stirring to make W10.
/I made a double emulsion. Thereafter, the paraffin was rapidly cooled to solidify, and the capsule and water were separated (single membrane capsule completed).

Next, this capsule was added to an aqueous solution of gelatin and gum arabic to disperse it, and then 10% acetic acid was added and r+H was gradually lowered to precipitate gelatin around the paraffin. Finally, curcuraldehyde, a protein hardening agent, was added to harden the seratin membrane, and the capsules were separated.

The double capsule thus obtained had a core of 20% ascorbic acid and 30.0% water, an inner layer of paraffin 2
0%, outer layer: 30% gelatin and a small amount of pigment.

0 Toothpaste composition Calcium carbonate 42.0% Saccharin
0.1% sorbitol
22.0% fragrance
1.0% ethyl paraoxybenzoate 0.
01% Sodium Lauryl Sulfate 1.3% Capsule 2.0% Water
30.5% As a comparison example, ascorbic acid 0.4% was used instead of the encapsulated product.
We also investigated the stability of toothpaste containing the same ingredients. The results are summarized below. The stability was determined by indophenol titration.

Stability of ascorbic acid Inventive product 1 Comparative example 2 days later 100% remaining Completely deactivated 7 days later 〃 14 days later Horns 21 days later 98% 28 days later 94% Example 2 Example 1 was applied to a dentifrice composition that did not contain an abrasive. The capsules used in the above were added to examine the stain removal effect. For comparison, a test was also conducted with no capsules added. The toothpaste composition and results are shown below.

0 Toothpaste composition Carbopol 1.9% 85% Glycerin 20.5 Sodium borate ]・7 Carbonate Sorta
0.7 Sodium zatukarin 0.2 Sodium lauryl sulfate 1.5 Sodium benzoate
0.3 fragrance
0.5 Capsules 1.5 Water 7120 Test Method Scaling was performed at the start of the test and at the time of sample replacement to obtain a stain adhesion rate of O.
A total of 2i1 each week! I brushed my teeth. After each sample was used, the stain (plaque) adhesion rate was observed.

0 Results The stain adhesion rate on the back side of the teeth was that of the present invention product 18.4 Comparative example 23. (n=5). That is, it can be seen that the product of the present invention exhibits an excellent stain removal effect even without an abrasive. It has been confirmed from other experiments that formic acid, acetic acid, dichloroacetic acid, trichloroacetic acid, tartaric acid, and malic acid, which are acids other than ascorbic acid, do not have an excellent stain removal effect.

Example 3 Various dentifrice compositions (compositions 1 to 1) containing the same capsules as those used in Example 1 were manufactured and their stability was examined. As a result, all of these compositions were stable for a long period of time. Composition ■～
The composition of X is shown below.

In the composition, CMC: hruboxymethylcellulose SDS Na nilauryl sulfate PEG: Polypropylene glycol MFP: Sodium monofluorophosphate IMP: Insoluble sodium meclate.

0 Composition I Ca diphosphate QCM
CO,5 carrageenan 0.5 sorbitol
15 Glycerin
15 Propylene glycol 2 S D S 1. Q Lauric acid jetanolamide 0.3 myristic acid
〃0.3 Tocopherol acetate 0.05 Methylparaben 0.05 Sodium benzoate
'Q, 3 Satsukarin Na
0.1 capsule
2.0 fragrance
1.0 water
Residual O composition ■ Ca diphosphate 5 Q silicic anhydride 3 CM C1,Q sorbitol 15 glycerin
10 Propylene Glycol 2 S D S 1. Q Lauroyl Sarcosine Na O82 Lauric Acid Jetanolamide 1.0 Methylparaben
0.05 Sodium benzoate
O,1 Saccharin Na O,
1 capsule 2.3 scents
Vehicle weight
1. O water
0 composition remaining ■ Aluminum hydroxide 40 Carrageenan 1.0 Alginate N
a Q, 5 glycerin
25 Propylene glycol 3 S D SO, 3 lauroylsarcosine Na 0.3 Myristic acid diethanolamide 0.5 Butylparaben
0.05 Sodium benzoate
Q, 3 Zatukarin Na Q, 1
Chlorhexidine hydrochloride 0. O1■9 Capsule 0.2 Fragrance
1,0 water
0 composition remaining ■ Aluminum hydroxide 40 Calcium carbonate 2 Carrageenan 1,0 Sorbit
30S D S
1. , 0 Lauric acid diethanolamide 1.5 Myristic acid 0.5 Tocopherol nicotinate o, i Butylparaben 0.05 Sodium benzoate
Q.5 Stevioside
0.1 capsule 0.2 fragrance 1.
0 water
0 remaining Composition V Calcium carbonate 45 CM C1,, 5 Sorbit 20 Glycerin
5 Propylene glycol 2 S D S 2. Q Lauric acid jetanolamide o, 3 myristic acid
〃043 Palmitic acid 〃o, 3 Butylparaben 0.1 Sodium benzoate
], 0 Stevioside
o, i tocopherol acetate
o, 1 capsule 2. Q
Fragrance 1
．． .

water
0 composition remaining ■ Calcium carbonate 45 Silicic anhydride 3 Carrageenan 1.07 )be
T
30 Propylene Glycol 2 S D S 3. .

Coconut oil fatty acid 0.3 palmitic acid diethanolamide 0.3 butyl paraben
0.02 Sodium benzoate
O, Q aspartame o, 1 tocopherol acetate o, 1 capsule
2. Q fragrance
1. Q water
0 composition remaining ■ Silicic anhydride 30 CM C1,0 Sorbitto 1° Glycerin
25 P E G 5S D S
O, 3 lauroyl sarcosine Na o, 5 lauric acid diethanolamide o, 5 myristic acid jetanolamide 0.5 Sucrose lauric acid monoester 10 Ethyl paraben
0.02 Sodium benzoate
0.3 Zatukarin Sodium
0.1 Tocopherol nicotinate 0.05
Chlorhexidine hydrochloride 0.001 capsule 2.0 fragrance
1.0 water
Residual O composition ■ Calcium pyrophosphate 50 Xanthan gum 1.0 Sorbit
30 Propylene glycol 2 S D S 1.5 Lauric acid diethanolamide 0.3 Myristic acid
〃0.5 PUB hydrogenated castor oil 1.0 Methylparaben 02 Sodium benzoate
0.5 Zatukarin Na
0.1 tocopherol acetate 0. I
M F P O, 76 capsules 2.0 fragrance
1.0 water
Residual O composition ■ MP50 CM C1,0 Sorbitsu 20 Glycerin
5 Propylene glycol 3 S D S 1.5 Palmitic acid diethanolamide 3.0 Lactitol monolaurate 0.5 Ethylparaben
0.1 Sodium benzoate 1.
Q Saccharin Na 0.1 Tocopherol Acetate 1.0MFP
O, 76 capsules 2.0 fragrance
1.0 water
0 remaining Composition X Carbopol 2.585% Glycerin 20.0 Sodium carbonate
i, QS D S
1. , 5 methylparaben 0.
1 Sodium benzoate 0.3 Sodium saccharin 0.1 capsule
2.0 fragrance
1.0 water
Remaining Example 4 A mouth rinse and a gingival pine surge cream containing the same capsules as those used in Example 1 were manufactured, and their stability was investigated. As a result, they were both stable for a long period of time. Their compositions are shown below.

0 mouthwash capsule 2.0% citric acid
0.3 Disodium hydrogen phosphate 0.7 Polyoxyethylene hydrogenated castor oil 5.
0 fragrance
1.085% Glycerin 10.0 Sodium Benzoate 0.5 Saccharin Sodium 0.2 Water
0 gum massage cream

Claims (4)

[Claims] (1) A double capsule with a structure in which a core material is a water-soluble drug selected from the group of vitamins, herbal medicines, and their extracts, which is coated with a lipophilic substance, and which is further coated with a hydrophilic substance. (2) Contains a double capsule with a structure in which the core is a water-soluble drug selected from the group of vitamins, herbal medicines, and their extracts, which is coated with a lipophilic substance, and which is further coated with a hydrophilic substance. An oral composition characterized by: (3) The oral composition according to claim (2), wherein the vitamin is ascorbic acid. (4) The oral composition according to claim (3), wherein the lipophilic substance is a wax-like substance and the hydrophilic substance is gelatin.