JPS62193638A - Granular agent - Google Patents

Abstract

PURPOSE:To hold powder for coloring and a medical effect component in a granule and to prevent the loss of its aesthetic appreciation effect and medical effect by blending inorganic acid salt and/or organic acid salt of chitosan as a mixing agent of powder to prepare a granular agent. CONSTITUTION:Chitosan is dissolved in an aq. soln. of inorganic acid and/or organic acid and various kinds of powder becoming a constitutional component of a granular agent are added to this soln. and kneaded. Then the granular agent is produced by granulating the obtained kneaded material and drying it. The blended amount of chitosan is varied by the kind and amount of the constitutional component of the granular agent but regulated to the range of 0.5-20wt%. Inorganic acid salt or organic acid salt of chitosan is salt of deacetylated substance (chitosan) of chitin. As the powdery particle blended to the granular agent, calcium secondary phosphate, insoluble sodium metaphosphate and calcium pyrophosphate, etc., are used.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to granules. More specifically, the present invention relates to a granule in which the cohesion of powder particles constituting the granule does not decrease even in the presence of water.

[Conventional technology]

The granule form is often used in the pharmaceutical and food fields. In some cases, it may be required that the granules retain their shape even in the presence of water. For example, granules incorporated into dentifrices fall under this category. The purpose of incorporating granules into dentifrices is to improve the aesthetic effect of dentifrices by turning coloring powder into granules, or to incorporate various medicinal ingredients into dentifrices. For example, the purpose is to prevent the particles from being strongly adsorbed in large quantities by fine particles such as abrasives.

On the other hand, granules are usually manufactured through the following steps.

Powder mixing → kneading → granulation → dry granulation → granulation In other words, powders of various active ingredients, excipients, colorants, etc. are kneaded in a solution containing a binder to form granules.

There are two types of binders used here: water-soluble and water-insoluble. Examples of water-soluble materials include starch, gelatin, gum arabic, methylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, and polyvinylpyrrolidone. Further, water-insoluble ones are used after being dissolved in an organic solvent, and examples thereof include ethyl cellulose and acetyl cellulose.

When granules made using a water-soluble binder are blended into an environment where water is present, such as in toothpaste dough, the moisture reduces the cohesiveness of the powder that makes up the granules, causing their shape to change. The problem was that it would collapse.

On the other hand, if a water-insoluble binder is used, although there is no problem of reduced cohesiveness as mentioned above, it requires the use of organic solvents in the production of granules, which can cause adverse effects on the human body and accidents such as fire. is a concern.

[Failure to solve the problem]

- In order to solve the problem described in F, the present inventors conducted extensive research in order to obtain granules that stably maintain their shape in an environment where water exists even though they contain a water-soluble binder. As a result, the present invention was completed.

That is, the present invention provides a granule having the following characteristics: an inorganic acid sulfate salt and/or an organic acid salt of chitosan is blended as a powder binder.

In the present invention, granules are aggregates of powder particles,
It means something that is so thick that its existence can be confirmed with the naked eye.

The inorganic or organic acid salt of chitosan (hereinafter simply referred to as chitosan salt) blended into the granules of the present invention is a salt of deacetylated chitin (chitosan).

Here, chitin is a polymer of N-acetel-D-glucosamine that exists in the shells of crabs, shrimp, insects, etc., and in the cell walls of mushrooms and molds.

The higher the degree of deacetylation of chitosan, the more amino groups there are in the molecule, and the fewer acetamido groups there are. In the present invention, any material that has been deacetylated to the extent that it can be dissolved in a dilute solution of an inorganic or organic acid can be used, but those with a degree of deacetylation of 60% or more are preferred.

Examples of inorganic acids used in preparing chitosan salt include hydrochloric acid, sulfuric acid, phosphoric acid, etc., and examples of organic acids include acetic acid, citric acid, malic acid, hexamaric acid, maleic acid, succinic acid, lactic acid, etc. It will be done.

Since the granules are manufactured in the presence of water, the powder particles added to the granules of the present invention need to be insoluble or sparingly soluble in water and acids. Specific examples include powders mainly used as abrasives in toothpaste such as dicalcium phosphate, insoluble sodium metaphosphate, calcium birophosphate, alumina, aluminum hydroxide, calcium carbonate, zeolite, anhydrous silicic acid, and hydrated silicic acid. Further examples include powders mainly used as excipients for granules, such as lactose, crystalline cellulose, starch, talc, nylon, and polystyrene.

The granules of the present invention are composed of the above water-insoluble or sparingly soluble powder as a base and chitosan salt as a binder, but in addition to these ingredients, various substances may be added to the granules depending on the purpose. It can be incorporated as For example, various inorganic or organic (natural and synthetic) pigments for coloring;
More specifically, inorganic pigments such as ultramarine blue, red iron oxide, and titanium oxide; natural food pigments such as paprika pigment and purple root; tar-based pigments that can be used in pharmaceuticals such as Red No. 3 and Blue No. 1, and their lakes; be.

In addition, various medicinal ingredients such as chlorhexidine hydrochloride, chlorhexidine gluconate, ε-aminocaproic acid, tranexamic acid, dihydrocholestanol, allantoin, allantoin chlorhydroxylaluminum,
Sodium monofluorophosphate, tin fluoride, phytic acid, dextranase, mutanase, grotease, lysozyme, sodium chloride, cetylpyridinium chloride, vitamin E1, ester of vitamin E, vitamin C
etc. can also be incorporated into the ingredients of granules.

If these pigments and medicinal ingredients are insoluble or sparingly soluble in water, they can also be used as the base of the granules of the present invention.

The granules of the present invention can be produced, for example, by the following method. That is, chitosan is dissolved in an aqueous solution of an inorganic acid and/or an organic acid, and various powders, etc. that will be constituent components of the granules are added to this solution and kneaded. Next, the obtained mixed wire material is granulated and dried to produce the product. As the granulation method, extrusion granulation method, spray granulation method, etc. can be used.

The amount of chitosan salt to be incorporated into the granules of the present invention can be determined depending on various uses. That is, as the amount of chitosan salt added increases, the disintegration strength of the granules also increases, so the amount of chitosan salt can be adjusted to provide a preferable disintegration strength depending on the use of the granules. In addition to the chitosan salt, the disintegration strength of the granules can also be adjusted by using the various water-soluble binders described above. For example, when the granules of the present invention are to be incorporated into a dentifrice, the disintegration strength of the granules is such that when the granules are incorporated into the dentifrice, their shape is maintained and It is preferable that it be easily disintegrated by the act of polishing. The amount of chitosan salt to be added for this purpose is
It varies depending on the type and amount of the constituent components of the granules, but the amount is 0.5
-20% by weight. For example, the constituent components are powders with an average particle size of 20 microns or less, and the degree of deacetylation is 60%.
In the case of granules using chitosan salt made of chitosan as described above, the amount of chitosan salt blended is preferably 1 to 5% by weight and 4%. In addition, the average diameter of the granules is 150 to 1,000.
Micron is appropriate.

[Action and effect of invention]

The granules of the present invention using chitosan salt as a binder have the advantage that since water is used as a solvent in the manufacturing process, there is no need for facilities such as fire prevention, which are required when organic solvents are used. Furthermore, unlike granules using ordinary water-soluble binders, their shape does not collapse in the presence of water, for example, due to moisture in toothpaste. Therefore, it is possible to retain the coloring powder and medicinal ingredients in the granules in the dentifrice, thereby preventing the aesthetic effect and medicinal effect from being lost.

〔Example〕

Next, the present invention will be explained with reference to Examples.

Example 1 Granules were produced using various binders and tested for granule shape retention when mechanically stirred in water.

(1) Materials ■ Powdered dicalcium phosphate dihydrate salt (Toyosu ■ Binder / Chitosan acetate [Prepared by dissolving chitosan (manufactured by Katakura Chinkarin ■, deacetylation degree 80% or more) in 1% acetic acid aqueous solution ] ・Carboxymethylcellulose sodium [manufactured by Daiichi Kogyo Seiyaku ■, trade name Celogen F-8EX dissolved in purified water: abbreviated as CMC-Na] ・Hydroxyethyl cellulose [manufactured by Daicel Chemical Industries ■, trade name f (EC- Use Unicell QP-4400H dissolved in purified water, HEC
(2) Manufacturing method of granules For 100 parts by weight of dicalcium phosphate dihydrate,
A binder solution was added so that the binder amount was 3.5 parts by weight, and the mixture was thoroughly kneaded, extruded through a 20-mesh sieve, granulated, and heated and dried at 90°C for 3 hours to produce granules. . Thereafter, the particle size was selected, and the particles that passed through a 25 mesh sieve and were captured on a 3° mesh sieve were used in the following experiment.

(3) Evaluation method for shape retention of granules In order to evaluate the shape retention of granules in water,
A disintegration tester (manufactured by Toyama Sangyo Co., Ltd.) specified in the Japanese Pharmacopoeia 0 revised edition was used. First, weigh out 50 μg of granules into an auxiliary tube, add this to 50 mM citrate phosphate buffer (pH 5,
0~s, o.

37° C.) and moved up and down at a frequency of 45 strokes per minute. After operating for 20 minutes, the amount of granules remaining in the auxiliary tube was observed and the shape retention was evaluated according to the following criteria.

Evaluation criteria: ○: Good (Most of the granules remain in the auxiliary cylinder) Δ:
Poor (about 2 granules remained in the auxiliary cylinder) ×: Extremely poor (almost no granules remained in the auxiliary cylinder) The results are shown in Table 1. As a result, the water-soluble binder C MC-N
Granules using a or HEC have poor shape retention, but the granules of the present invention using chitosan acetate have excellent shape retention.

Furthermore, when similar tests were conducted using chitosan hydrochloride, phosphate, citrate, and succinate, almost identical results were obtained.

Table 1 Example 2 100 parts by weight of 4A type zeolite powder (manufactured by Kao ■, average particle size 2 microns) and ultramarine blue (manufactured by Wako Tsumugi Pharmaceutical ■) as a coloring agent.
The single layer ridge was thoroughly mixed. To this was added 3 parts by weight of chitosan (same as in Example 1) dissolved in a 1% acetic acid aqueous solution, and these were kneaded. This clay-like mixture was granulated by extrusion through a 20-mesh sieve, and dried at 90° C. for 3 hours to obtain granules. Further, large particles were removed through a 20-mesh sieve, and powder was removed through an 80-mesh sieve to obtain blue granules. By incorporating this granule into a dentifrice, it is possible to obtain the tartar prevention effect of zeolite and the esthetics of ultramarine blue.

Example 3 10 parts by weight of silicic anhydride and 1 part by weight of paprika pigment (manufactured by Hydrate Bussan ■) were mixed with 50 parts by weight of allantoin chlorhydroxyaluminum (Yobin Fine Chemicals (manufactured by Kiki),
Two parts of chitosan (same as in Example 1) dissolved in a 1% acetic acid aqueous solution was added to this and kneaded. This clay-like mixture was extruded through a 20-mesh sieve and granulated at 90°C.
The mixture was heated and dried for a period of time to form granules, which were then passed through a 20-mesh sieve to remove large particles, and then through an 80-mesh sieve to remove powder to obtain orange-red granules. By incorporating this granule into a dentifrice, it is possible to obtain the gingivitis preventive effect of allantoin chlorhydroxyaluminum and the aesthetic properties of paprika pigment.

Example 4 5 parts of lactose in 1 part by weight of sodium phytate (manufactured by Sigma)
0 parts by weight and chitosan (same as Example 1)
Two parts by weight were dissolved in a 1% acetic acid aqueous solution and added, followed by kneading. This clay-like mixture was granulated by extrusion through a 20 mesh sieve, and dried by heating at 90°C for 3 hours to obtain granules. Furthermore, large particles are removed through a 20-mesh sieve.
Further, powder was removed using an 80-mesh sieve to obtain white granules.

If this granule is added to a dentifrice, the tartar preventive effect of sodium phytate can be obtained.

Reference Example 1 2 parts by weight of the granules obtained in Examples 2 to 4 were added to 98 parts by weight of dentifrice materials 1 and 2 shown below, and the mixture was deaerated and stirred at room temperature for 10 minutes to produce a granule-containing toothpaste. The drug was manufactured. At this time, the granules of Examples 2 to 4 all maintained their shapes well. Further, when an accelerated test was carried out in which the dentifrice containing granules was filled into a laminated tube and stored at 40°C for 30 days, the shape of the granules was completely retained even after storage.

Toothpaste fabric 1> Dibasic calcium phosphate dihydrate salt 40 Glycerin by weight 1070% sorbitol 14 Sodium carboxymethyl cellulose 2 Sodium lauryl sulfate
1.5 Satucalin Sodium
0.2 fragrance
0.8 Purified water Appropriate amount 100% by weight <Toothpaste dough 2> Silicic anhydride 20 Heavy tiglycerin 3070% Nlubitol 30 Sodium carboxymethyl cellulose 2 Sodium lauryl sulfate
1.5 Satucalin Sodium
0.1 fragrance
0.7 Purified water appropriate amount 100% by weight or more

Claims (1)

[Scope of Claims] 1. A granule comprising an inorganic acid salt and/or an organic acid salt of chitosan as a binder for powder. 2. The granule according to claim 1, which is for use in toothpaste formulation.