JPS61192750A - Aqueous gel composition - Google Patents

Abstract

PURPOSE:To provide an aq. gel compsn. which has good storage stability and thixotropic properties, can be readily wiped out after coating, has a proper yield value and is suitable for use in preventing tooth decay by a tray method, containing a composite of a water-soluble anionic high-molecular gum and crystalline cellulose and a fluorine-contg. component as essential components. CONSTITUTION:A compsn. contains a composite obtd. by intimately combining a water-soluble anionic high-molecular gum with crystalline cellulose, and a fluorine-contg. component as essential components and optionally, a pH adjustor and additives. Examples of the water-soluble anionic high-molecular gum are cellulose derivatives and natural gum, and sodium carboxymethylcellulose is particularly preferred. Crystalline cellulose can be obtd. by the acidic hydrolysis of cellulose or the oxidative decomposition of cellulose with an alkali. Examples of the fluorine-contg. components are potassium fluoride and sodium fluoride. As said pH adjustor, phosphoric acid and/or its salts are preferred.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to an aqueous gel composition used as a topical application for preventing steel corrosion. More specifically, the present invention relates to an aqueous gel-like composition that can be used in the tray method in a tooth surface coating agent containing a friend compound for the purpose of preventing hard corrosion.

(Prior Art) A technique of applying fluoride to one tooth surface is becoming popular in order to prevent tooth movement in infants and other humans. The effectiveness of applying fluoride to prevent one-touch exposure has already been clinically confirmed, but there are two methods for applying it.

One is the so-called happy liquid application method, in which a cotton swab or cotton ball is impregnated with a solution containing fluoride, cleaned with it, dried, and then applied to the specific tooth surface. In this tray method, a fluoride-containing gel similar to K1 toothpaste is injected into a container (tray), and the whole tray is applied to the tooth surface to allow fluoride ions to penetrate into the tooth enamel.

Compared to the solution application method, in which it is necessary to apply the fluoride ions to the tooth surface many times with a cotton swab or cotton ball over a period of several minutes in order to achieve sufficient penetration of the fluoride ions into the tooth surface, the tray method requires Since the tray can be applied to the upper and lower tooth surfaces and left as is for the required time, it has excellent operability during application, making it particularly practical for touch prevention targeting infants.

The present inventors have focused on the future potential of these gels for preventing caries that are applied using the tray method, and have been conducting clinical studies on their effectiveness as well as conducting improvement research that takes into account the practical properties of the gels.

For details, see “Microcrystalline C
About the characteristics of fluoride gel using e1lulose
"Study on topical application of fluoride gel (first report)": Dental Journal, Vol. 85, At 1.
152-155 (1983), ``Characteristics of thixotropic fluoride glue and its reactivity with the enamel surface layer''; Journal of the Oral Hygiene Society, Vol. 34, No. 4, pp. 90-91 (Showa 5
As disclosed in September 2009).

The present inventors used crystalline cellulose (Avicel ■, manufactured by Asahi Kasei Industries, Ltd.) as a gelling agent to prototype a practical gel containing fluoride as disclosed in the above-mentioned research report. I was somewhat successful. These gels are
If a medical practitioner prepares the mixture each time it is used and uses it within a short period of time, it has satisfactory practical properties, but if it is mass-produced, distributed on the market, stored for a long period of time, or used from a container. When viewed as a commercial product that requires long-term quality assurance, in which small quantities are taken out each time and every last drop is used, drastic improvements such as syneresis may occur during long-term storage. It was something to do.

(Problems to be Solved by the Invention) In addition to solving the above problems, the inventors endeavored to improve the necessary characteristics described below, and completed the present invention.

The gel used in the tray method must have the following properties. In other words, it has excellent fluidity and penetrates well into the narrow interproximal spaces @IfC when the tray is attached. For this purpose, the gel should have chicken-tropic properties. In order to prevent swallowing, it should have an appropriate yield value and not flow out in a stationary state. After application to the tooth surface, gargling is not possible for several tens of minutes to enhance the application effect of fluoride ions, so it is easy to wipe off after application.

(Next means to solve the problem) A gel for preventing corrosion that satisfies the above items and whose quality does not change over a long period of time can be produced by having the following composition. , unreleased FJ
Completed A.

In other words, it is an aqueous gel-like product that contains a complex formed by tightly combining a water-soluble anionic polymer gum and crystalline cellulose, and a fluorine component as essential components, with a pH adjuster and other additives added as necessary. It is a composition.

The constituent elements of the present invention are detailed as follows.

The water-soluble anionic polymer gum of the present invention includes cellulose derivatives such as sodium carboxymethylcellulose and sodium carboxymethylethylcellulose, natural gums such as pectin, karaya gum, carrageenan, sodium alginate, and furcelleran, and microbially fermented gums such as xanthan gum. It refers to Among these, sodium carboxymethyl cellulose (hereinafter abbreviated as CMC) is the most preferred because it is an industrial product and is inexpensive. The above gums can be used alone or in combination of two or more.

The crystalline cellulose of the present invention refers to a cellulose crystallite aggregate having a substantially constant degree of polymerization obtained by acid hydrolysis or alkaline oxidative decomposition of cellulose, and for example, industrial and engineering chemistry, Volume 42 (1950), pp. 502-50
It is as defined in Mr. O. Ni Batista's rutsaki on page 7.

A close union of the ionic polymer gum and the crystalline cellulose can be obtained by grinding and kneading the two in the presence of moisture, followed by drying. For the grinding and kneading, a known grinding and kneading machine having a displacement b may be used. For example, there are kneaders, planetary mixers, extruders, three-roll mills, colloid mills, homogenizers, etc., and a suitable model can be selected depending on the water content in the grinding and kneading process.

In the case of the present invention, it is preferable to grind so that the average particle size of the crystalline cellulose after grinding and kneading is 8 microns or less in Stokes diameter, preferably 5 microns or less.

Drying after grinding and kneading may be performed by any known method. The moisture content of the composite after drying is usually about 2%.
It is controlled to 15% or less.

The composite after drying can be pulverized, sieved, and classified by known methods.

Furthermore, the composite composition is preferably as follows. That is, the blending ratio of water-soluble anionic polymer gum and crystalline cellulose is 5/95 to 50 by weight.
If the weight of the water-soluble ionic polymer gum is less than 5%, satisfactory colloidal dispersion of crystalline cellulose cannot be achieved when dispersed in water to form an aqueous gel. , the aqueous glue of the present invention has 1f over time
c@ - It becomes something with a lot of water. When the weight of the water-soluble ionic polymer gum exceeds 50% by weight, the water-based gel of the present invention has a small yield value, a reduced anti-slip effect, and a high viscosity. The gel flows to the adjacent surface and becomes separated, and the wiping property after application becomes poor.

The amount of the above-mentioned complex added to the aqueous gel composition of the present invention is about 1.0 to 10% by weight, preferably about 2.0% by weight.
~7.0wt1 more preferably about 4.0-6.0wt-
should be within the range of

If the amount of the composite added is less than about 1.0% by weight, syneresis of the aqueous gel of the present invention cannot be prevented and an appropriate yield value cannot be imparted.If the amount of the composite added exceeds about 10% by weight, the aqueous Since the gel impairs fLwJ properties, it is inconvenient to apply it to a tray and attach it to the tooth surface.

The fluorine component referred to in the present invention refers to a compound that brings fluorine ion (F-)ffi to the aqueous gel composition that is the final product, and potassium fluoride, sodium fluoride, tin fluoride, etc. are used. can.

Regarding the amount of fluorine component added, the higher the degree of fluorine ion, the better the penetration of fluorine ions into the tooth enamel, so it is best to control the amount of fluorine component added on the high side. For example, taking sodium fluoride, 1 part water
The solubility in 00 fVC is about 41 at room temperature, and addition beyond this is practically meaningless. That is, the upper limit of the amount of the fluorine component added to the composition is determined by its solubility in water.

In the case of the aqueous gel composition of the present invention, it is necessary to maintain stable quality for a long period of time even when the product temperature rises and falls during the product distribution process. In order to avoid this, the solubility in water should be very close to the
Rather, for example in the case of sodium fluoride, about 1. Q~3.
A range of 0 weight or more is preferable, and this range is sufficiently effective in preventing caries.

The pH adjusters referred to in the present invention include S;rensen's buffer, Michaelis' buffer, C1ark and L
uba buffer, Kolthoff's buffer, Mcll
vaine's buffer, Menzel's buffer, Walp
Refers to inorganic or organic acids, alkalis, and salts that can be adjusted to a specific pH range either alone or in combination, as used in the case of oleic buffers. It will be appreciated that the compositions of the present invention are suitable for pediatric VC21
1, so those with a pungent odor are not appropriate, and odorless or 4IL aesthetics are preferable. Since it is applied to the oral cavity, it is preferable to use something that is safe even if supplemented by any chance.In this sense, phosphoric acid and phosphates, or citric acid, lactic acid, and tartaric acid. , malic acid, adipic acid, and their salts may be used alone or in combination. In the case of the present invention, phosphorus a! Or/and phosphates are more preferred from the viewpoint of not only meeting the above requirements but also promoting the penetration of fluoride ions into enamel.

The above-mentioned pH adjuster is added so that the OpH value of the gel composition of the present invention is in a range of about 3.0 or more. If the pH value is less than about 3.0, it is undesirable because it has a too sour taste, and there are also problems such as agglomeration and precipitation of the composite and damage to tooth enamel due to repeated application. pf15. Regarding the range exceeding Of, it can be practically used up to the neutral range except for alkaline side, but for reasons such as antifungal effects, it is more preferable to use the weakly acidic range, specifically up to pH 5.5.

In the present invention, other additives may be added as necessary, such as lemon oil, orange oil, vanilla essence, strawberry essence, etc., sucrose, glucose, fructose, sorbitol, maltitol, coupling sugar,
Naturally derived or synthetic sweeteners such as glycyrrhizin, stevioside, saccharin, aspartame, and thaumatin; humectants such as sodium lauryl sulfate, norbitan fatty acid ester, sucrose fatty acid ester, propylene glycol fat Ill x methyl, polyethylene glycol, and propylene glycol; sodium alginate,
Natural or synthetic thickeners such as alginate phlopylene gellicol ester, hydroxypropylcellulose, polyvinyl alcohol, methylcellulose, carrageenan, karaya gum, pectin, guar gum, locust bean gum, xanthan gum, starch phosphate, benzoic acid, Preservatives such as sorbic acid, propionic acid #i/* and their salts, and various natural or artificial food coloring agents may be added at will.

Examples of practical methods for producing the composition of the present invention are as follows.

Purified pulp for rayon 1 was shredded into #' pieces, immersed in 2.5N hydrochloric acid solution at a bath ratio of 30, hydrolyzed at 105C for 15 minutes, and after separating the hydrolysis residue t-F, washed with pure water. , crystalline cellulose with a moisture content of 50 or more as a solid content of 0.
75ky was recovered.

The above wet crystalline cellulose is 1.34 on a wet basis.
9 samples, CMC (medium viscosity product, D, 8. = 0.75
)0.152 to 9<moisture content 1o%) and 5 in a kneader
After grinding for 2 hours, the mixture was dried, ground, and sieved to obtain a composite with a crystalline cellulose/CMC ratio of 85/15 by weight.

Sodium phosphate 10f1 Sodium fluoride 10t5 Ethanol (95%) 1t1 Saccharin 0.15t Lumon oil 0.1t, Sodium lauryl sulfate o, o s y
2. Preliminarily dissolve in 750 f pure water, and add the complex 6.
After adding Off and stirring for 30 minutes with a high-speed stirrer, a phosphoric acid aqueous solution in which 5 tons of phosphoric acid was dissolved in pure water was gradually added dropwise, and stirring was continued for another Kso minutes until the total amount was 100Of. The aqueous gel composition of the present invention is obtained by adding pure water and adjusting the composition to obtain the following. The pH of the composition was approximately 5.1.

The method for evaluating the aqueous gel composition of the present invention is as follows.

Evaluation method (1) Storage stability - Fill a 250-volume glass bottle with 200 ml of the sample, seal it, and leave it at room temperature. Observe the presence or absence of syneresis every 1, 3, 6, and 12 months (storage-stable residents).

(2) Fill a sample T-250-sized glass bottle with 201111F. (2) After sealing the bottle, conduct an abuse test for 5 cycles in which the sample is kept at 40C for 1 week and then at 5C for 1 week, and the presence or absence of syneresis is observed.

(2) Yield value In order to prevent the gel from dripping or flowing out of the tray in a stationary state, it is necessary that the gel has a yield value.

The yield value can be measured using a cone-plate rheometer, but as a simple and practical evaluation method, the following method is used.

Take a small-diameter vinyl tube at the tip and fill it with gel into a syringe with an inner diameter of 22-1 and a length of 20031.
Fill a 1m test tube with about 151, tap it lightly, and add 2
Keep quiet for 4 hours. After standing still, the test tube is turned horizontally or inverted, and the gel flows in the test tube and the time taken to see if it flows out from the test tube opening is observed.

(3) KFi, in which the gel injected into the thixotropic tray penetrates well into narrow interproximal surfaces;) When the tray is attached to the tooth surface, the gel must flow well. Moreover, it is best to use something that does not leak or drip after being worn. In order to meet these characteristics, it is necessary to have a larger gel than Chicken Trobby.

Various methods have been proposed for measuring chicken tropism, but in the present invention, a cone-plate rheometer is used.
(Hitachi Shear Rheometer, IGK-120), the sliding speed was raised and lowered in the range of t0 to 1100, and the shear force speed was determined. compared the size of.

(4) Adhesion (amount of adhesion) Adhesion (amount of adhesion) is used as an evaluation measure for gel-like compositions that have good contact with the tooth surface and are easy to wipe off after application. It was measured by the following method.

Transfer the sample to a rheometer (Fudou Kogyo Co., Ltd. NRM-2002)
Jfi) The sample was placed on a sample stand, an adapter for measuring the degree of adhesion was inserted, and then pulled up. At that time, the amount of gel that adhered to the adapter surface was divided by the insertion surface area of the adapter, and this was used as a measure of adhesion.

Needless to say, this is a measure of the amount of gel remaining on the tooth surface when the tray is removed from the tooth surface and when the tooth surface is wiped with absorbent cotton after application, in other words, the wiping ability of the gel. be.

(Example) Example 1: Production of a composite DP pulp (average polymerization [1, QQQ) was hydrolyzed in a 2.5N aqueous hydrochloric acid solution for 1050 minutes for 15 minutes, then overwashed, and the crystalline cellulose in a wet state was Nine points.

The average particle diameter of this material was determined by Shimadzu Corporation IA.

The particle size was measured using a centrifugal sedimentation particle size distribution analyzer CP-SOW, and the particle size was about 20 J. A wet crystalline cellulose and a water-soluble anionic polymer gum were prepared in the formulation shown in Table 1. After blending and grinding in a kneader for 1 hour (
At this time, the average particle size was all below 8μ), the obtained dry lumps were finely loosened, dried in a hot air dryer at 60C until the moisture content became 10 ml, coarsely crushed in a crusher, and then crushed in a hammer mill. and passed through a 5G mesh sieve to obtain complex A-C.

Table 1 Compound formulation As a comparative example, guar gum, which is a water-soluble nonionic polymer gum, is mixed with crystalline cellulose at a blending ratio of 10/90. A separate large complex was created.

Example 2 An aqueous gel composition was prepared according to the formulation in Table 2. The manufacturing procedure is as follows.

Table 2 Aqueous gel composition formulation Pour the complex into pure water and finely disperse it using a lab mixer.

Probyle/glycol is added, and after stirring, sodium fluoride and sodium phosphate are added, and after thoroughly stirring the whole, phosphoric acid (25 s aqueous solution) is gradually added while stirring, and the whole is further stirred for 1 hour at Vc.

As the laboratory mixer to be used, for example, one capable of applying shearing force, such as the Tokushu Kika Kogyo (Kiki-made T, K, Homo mixer) is preferable.

Table 3 shows the evaluation results of the obtained gel.

Table 3 Aqueous gel evaluation results From the results in Table 3, N12, Nn5 e Nn4,
It can be seen that each of the aqueous gels of Nh6 and Na7 gives good values.

Example 5 Aqueous gels with varying amounts of the complex added were produced according to the formulations in Table 4 according to Example 2, and evaluated. The evaluation results are shown in Table 5.

Table 4 Aqueous gel composition formulation Table 5 Aqueous gel evaluation results (Note) The water was tilted horizontally to check for outflow.

If the tray method is used, in which the tray is injected and attached to the tooth surface, the electric power 1. Electricity 20%8 was judged to be inappropriate. N113
Although there was water separation during landing and drying, and the yield value was weak, it was judged that it could be used in actual use.

Example 4 Composite C described in Example 1, crystalline cellulose ■ Avicel JpH-501 [manufactured by Asahi Kasei Industries] and carboxymethyl cellulose sodium (Japanese Pharmacopoeia compliant product) were used as gelling agents, and Table 6 Aqueous gels were prepared and evaluated according to the formulation.

To create an aqueous gel, add all ingredients except phosphoric acid to water,
After stirring with a lab mixer, phosphoric acid was added, stirring was carried out again, and the mixture was passed through a piston-type pomodgenizer twice under a pressure of 150 kg/at.

Table 7 shows the evaluation results.

Table 6 Aqueous gel composition formulation Table 7 Aqueous gel evaluation results (Note) The water was tilted horizontally to check for outflow.

*Electric 2 and -3 are comparative examples.

As is clear from the above, Nn1 according to the present invention can withstand long-term storage, has good yield value and chicken peak lobby property,
Adhesion was low (wiping property was good). Comparative controls, crystalline cellulose-only system and CMC-only system, are both inferior to the present invention in two points, storage stability and yield value, and in particular -5
The CMC system had high adhesion.

Comparative Example 1 Commercially available crystalline cellulose [Avicel JpH-101 [manufactured by Asahi Kasei Kogyo ■] and Japanese Pharmacopoeia compliant CMC were blended in a ratio of 9/1, and in the formulation shown in Table 4 of Example 5, the complex (A- 3)
Aqueous gels were produced and evaluated using them as gelling agents instead of.

The resulting aqueous gel has poor storage stability, low yield value, flows out within 30 seconds, low chicken tropism, and adhesiveness of 14.5~/-! It was huge.

(Effects of the Invention) It is clear from the above description that compared to the conventional gel for preventing dental caries produced using crystalline cellulose as it is, crystalline cellulose and water-soluble anionic polymer gum are The anti-erosive gel of the present invention, which uses a composite obtained by grinding, kneading, and drying in the presence of water, does not cause syneresis even after long-term storage, and has (2
1. Due to its high thixotropy, it penetrates into the narrow interproximal spaces when the tray is attached, has an appropriate yield value, does not drip or flow out of the tray in the resting state, and ( 4: Wipeability after application is also improved.

Claims (6)

[Claims] (1) An aqueous gel composition whose essential components are a complex formed by closely combining a water-soluble anionic polymer gum and crystalline cellulose, and a fluorine component. (2) The aqueous gel composition according to claim 1, wherein the water-soluble anionic polymer gum is sodium carboxymethylcellulose. (3) The aqueous gel composition according to claim 1, wherein the amount of the composite added is about 1.0 to 10% by weight, preferably about 2.0 to 7.0% by weight. (4) The aqueous gel according to claim 1, wherein the fluorine component contains about 0.5 to 4.0% by weight, preferably about 1.0 to 3.0% by weight of sodium fluoride. Composition. (5) A pH adjusting agent is added to a complex formed by tightly combining a water-soluble anionic polymer gum and crystalline cellulose and a fluorine component, so that the pH is in the range of approximately 3.0 to 5.5. An aqueous gel composition. (6) The aqueous gel composition according to claim 5, wherein the pH adjuster is phosphoric acid.