JPS6147401A - Calcium phosphate based sustained release substance - Google Patents

Abstract

PURPOSE:The titled sustained release substance effectively sustaining an action of a release material for a long period, adhering the release material on a support composed of a calcium phosphate based compound having a specific Ca/P molar ratio and specific surface area in a specified range measured by BET method. CONSTITUTION:A calcium phosphate based sustained release substance prepared by adhering the release material (at least one selected from a deodorant, germicide, agricultural chemical, medicine, antioxidant, tasting material, insect expellent, plant growth regulater, food preservative agent, peroxide, ultraviolet ray absorbant, fungicide or vaporizing rust inhibitor) on a support composed of a carium phosphate based compound (used as either powders, as they are, in a vessel or pressure-moldings without using any bider) having 1.0-2.0, particularly 1.5-1.7molar ratio (Ca/P), and 50-300m<2>/g, especially 100-250m<2>/g specific surface area measured by BET method.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a sustained release product based on a calcium phosphate compound.

Conventional technology There are known sustained-release materials in which substances to be released, such as fragrances, deodorizers, and disinfectants, are adsorbed onto a sustained-release material (activated carbon, silica gel, felt, sawdust, synthetic resin composite) as a base material. It is. The main properties required for sustained release substances are:
There are the following.

■ Capable of adsorbing a predetermined amount or more of the substance to be released, ■ Excellent retention of the adsorbed substance to be released, and releasing the substance to be released little by little over a long period, ■ No chemical effects on the adsorbed substance to be released. Do not cause any change.

Flavors, deodorizers, disinfectants, and the like used as substances to be emitted are effective due to their volatility. However, in known sustained release substances, substances with a large amount of adsorption tend to be unsuitable for long-term use because they have poor retention of the substance to be released, and they also tend to be unsuitable for long-term use. In some cases, it may cause

In view of the current situation, the present inventor has conducted various researches on Kasui, and found that Ca is in the range of 1.0 to 2.0 moles per 21 moles, and the specific surface area' by the BET method is 5θ to 21 moles. 300
Calcium phosphate compounds within the range of m/g are
It has been discovered that when the substance to be released is a fragrance, it has all of the properties (■ to ■) required of the sustained release substance described above,
Based on this knowledge, we have already applied for a patent
556).

As a result of further research, the present inventors found that the calcium phosphate-based compound described above satisfies the properties required as a sustained-release material of (1) to (4) above for substances to be released other than fragrances, Here is the book) The completion of the starting order is - That is, the present invention is based on Ca/P (molar ratio) = 1.0 to 2.0
, BET method A substance to be emitted (
This relates to a sustained-release product made by layering ingredients (excluding fragrance).

In the present invention, Ca/P (molar ratio) = 1.0-2.01 Specific surface area by BET method = 5
It is essential to use a calcium phosphate compound having a concentration of 0 to 300 Fff22/g as the base material. Ca/P
(molar ratio) is less than 1.0 or more than 2.0, there is a tendency for the adsorbed substance to be released to change in quality. Ca/P (molar ratio) is preferably 1.5 to 1.7.

Calcium phosphate having a Ca/P (molar ratio) of 1.5 to 1.7 is known as hydroxyapatite.

Furthermore, if the specific surface area determined by the BET method is less than 50 m22/g, the adsorption amount of the substance to be released is insufficient, whereas if it exceeds 300 m22/g, the adsorption amount is sufficient, but retention and On the contrary, sustained release properties tend to decrease. The specific surface area is more preferably 100 to 250 m2/g. Calcium phosphate compounds can be used as powder in a container, or they can be pressure-molded without using a binder.
You may do so.

Furthermore, it is also good if it is mechanically granulated using a granulator.

In addition, the base material made of the calcium phosphate compound is molded with a binder made of a water-soluble polymer and the diameter is
It may be used as a spherical molded body of about 10 mm. When used as a spherical molded article, the destruction phenomenon of the sustained release material when impregnated with the substance to be released is reduced without causing any damage to the quality and properties of the sustained release material described in (1) to (4) above. It is preferable that the spherical molded body is manufactured by a well-known liquid curing method, which is known as a method for manufacturing microcapsules. For example, Ca/
When using hydroxyapatite with P (molar ratio) of about 1.5 to 1.7 as a base material, the hydroxyapatite contains an aqueous hydroxyapatite suspension, a water-soluble polymer, and a fibrous substance if necessary. The mixture is dropped into a bath containing a curing agent for the water-soluble polymer through an orifice, cured in the bath, washed with water, dried,
A spherical molded body can be obtained. The particle size of the molded body is determined by the pre-concentration of the water-soluble polymer in the mixture (i.e., the particle size of the mixture),
It can be arbitrarily adjusted by adjusting the droplet diameter, dropping distance, etc. Water-soluble polymer-hardening agent systems include alginate Ca++ (calcium ions derived from water-soluble calcium salts such as calcium chloride and calcium nitrate);
polyvinyl alcohol - borax or formaldehyde,
Examples include carboxymethylcellulose-Fe8+. The amount of water-soluble polymer to be used relative to the calcium phosphate compound is usually 1 to 10 parts by weight per 100 parts by weight of the former.

When used as a spherical molded body, a fibrous substance may be used in combination with a binder. This fibrous material more effectively prevents the destruction of the sustained release material when impregnated with the material to be released, and increases the amount of adsorption of the material to be released by increasing the number of communicating holes in the sustained release material. It improves its retention and exhibits sustained release over a longer period of time. Such fibrous materials include various natural and synthetic fibers, including protein fibers such as silk and wool, cellulose fibers such as cotton, linen, and pulp, mineral fibers such as asbestos, and polyamide fibers. type, polyester type, polyacrylonitrile type,
Examples include synthetic fibers such as polyvinyl alcohol-based and polyvinylidene chloride-based fibers.

The fibrous substance has a length of about 100 to 350 μm and a thickness of 10
It is preferable to set it to about 50 micrometers. The amount of fibrous material used relative to the calcium phosphate compound is usually 1.
The amount is preferably 5 to 20 parts by weight per 00 parts by weight.

Substances to be adsorbed and held in the sustained release body of the present invention are substances that volatilize or sublimate in the atmosphere under normal conditions, and substances that diffuse outside the sustained release body in the presence of moisture or by heating. In the present invention, such substances include deodorizers, disinfectants, agricultural chemicals,
Use materials selected from pharmaceuticals, antioxidants, ultraviolet absorbers, taste substances, fungicides, insect repellents, volatile rust inhibitors, plant growth regulators, food preservatives, peroxides, etc. Specific examples of each are illustrated below.

(1) Deodorizer: tannic acid, ginger brain oil, turpentine oil,
Natural fulvic acid.

(2) Disinfectants: isobrothiolane agent, carpendazole agent, sodium hypochlorite, hypochlorous acid.

(3) Pesticide Nidimethyl phthalate, 2-ethyl-1
゜3-hexanediol, indalone, dimethyl carbamate, irgavirin, PO2 agent (pentachlorophenol), MEP agent (dimethylthiophosphate)), EC
P agent (diethyldichlorophenylthiophosphate),
Chloropyrine, cerebrum, naphthalene, valadichlorobenzene, metaldehyde, β-(2-(3,5-dimethyl-2-oxo-cyclohexyl)-2-hydroxyethyl)glutarimide.

(4) Pharmaceuticals: Vitamin A, Vitamin D, Vitamin E
.

Vitamins include phenolsulfonic acid, phenylpentol, diflucortolon valerate, flumethacin biparate,
Exalamide, cyclovirox olamine, cytucanin.

(5) Antioxidants: 4,4'-thiobis-(3-methyl-6-t-butylphenol), dilaurylthiodipropionate, pentaerythrityltetrakis-(3-(
3,5-di-t-butyl-4-hydroxyphenol)
Propionate.

(6) Ultraviolet absorber: 2.4-dihydroxybenzophenone, phenyl salicylate, 2-(2'-hydroxy-5'-methyl-phenyl)-benzotriazole, 2
-ethylhexyl-2-cyano-33-diphenylacrylate.

(7) Taste substances: citric acid, lactic acid, malic acid, saccharin, stevioside, sorbitol, brucine, quinine, caffeine.

(8) Antifungal agents: salutylanilide, 2,2'-dioxy-5,5-dichlorodiphenylmethane, ortho-phenylphenol, diphenyl, thiabendazole, alkylpolyaminoethylglycine hydrochloride.

(9) Insect repellent: piperonyl butoxide.

00 Volatile rust inhibitor: trimethylsulfonium nitrite, diisopropylammonium nitrite, 1,2゜3-
Benzotriazole.

Op Plant growth regulator: Bee agent, (6-(N-benzyl)aminopurine), gibberellin, Relabone agent.

(2) Food preservatives: sodium dehydroacetate, sodium propionate, lauryltrimethylammonium-2
,4,5-trichlorophenoxide.

(To) Peroxide Hydrogen diperoxide, chlorine dioxide, t-butyl hydroperoxide, dicumyl peroxide, tetralin hydroperoxide, t-butyl perbenzoate, di-t-butyl peroxide, 2.5- dimethyl-
2,5-di(t-butylperoxide)hexane.

The sustained release material of the present invention, which adsorbs and holds the various substances to be released, can be produced by adsorbing the substance to be released onto the calcium phosphate simultaneously with or after the production of calcium phosphate. Representative examples of the method include the following.

(a) During the production of calcium phosphate, a desired substance to be released is added to an aqueous medium, and a reaction for producing calcium phosphate is carried out.

) @ Add the material to be released to the aqueous suspension of calcium phosphate produced.

(C) A powder product of calcium phosphate is sprayed with a solution in which the substance to be released is dissolved in an appropriate solvent, or the powder product is immersed in a solution in which the substance to be released is dissolved in an appropriate solvent.

(ψ Spray a liquid in which the substance to be released is dissolved in an appropriate solvent onto a molded body of calcium phosphate, or immerse the molded body in a solution in which the substance to be diffused is dissolved in an appropriate solvent.

In the sustained release material of the present invention, the substance to be released that has been adsorbed to the saturation adsorption amount of calcium phosphate is usually almost completely adsorbed and retained. The adsorption amount of the substance to be released is appropriately determined depending on the type of the substance to be released, the rate of volatilization of the substance to be released from the sustained release body, the intended use of the sustained release body, and the like. In general, the adsorption amount of the substance to be released is 0.00000000000000000000 for 100 parts by weight of calcium phosphate.
The amount is preferably 0.012 to 80 parts by weight.

The sustained release material of the present invention does not cause alteration or deterioration of the substance to be released that has been adsorbed over a long period of time, and releases the substance to be released at an appropriate rate. Therefore, the sustained release material of the present invention can effectively sustain the action of the substance to be released over a long period of time. The sustained-release material of the present invention is effective for various uses, depending on the type of substance to be released, such as a deodorizer for refrigerators, toilets, lockers, etc., a softening agent for vegetables, fruits, etc., sterilization for fur, etc., and an insect repellent.

Example 1 Calcium hydroxide aqueous suspension with a concentration of 10% by weight 7.4Kf
9 was added to 1.47 g of an aqueous phosphoric acid solution having a concentration of 40% by weight to form hydroxyapatite, which was dried and crushed to obtain powdery IKF. This hydroxyapatite is Ca
/P (mole ratio) = approximately 1.64, and specific surface area by BET method = 180 m2/f. 2.5 da of a 4096 aqueous solution of tannic acid (deodorant) was added by spraying to the thus obtained hydroxyapatite powder 1 (l) to prepare a tannic acid adsorbed hydroxyapatite 7 (tight sustained release material).

In order to test the deodorizing power of this sustained release material, an air washing bottle (capacity 3007F+) containing 150 ml of 10% ammonia water was used.
While flowing N2 gas from one side of 1) at a rate of 5001 nl/min, a column filled with the sustained release powder was attached to the other outlet, and the ammonia passing through the column was poured into an aqueous solution of hydrochloric acid with a pH of 4. The amount of ammonia passing through was determined by determining the change in pH over time. The results are shown in Table 1.

Example 2 Calcium hydroxide aqueous suspension with a concentration of 10% by weight 7.4KF
1.47 Kf of phosphoric acid aqueous solution with a concentration of 40% by weight was added to form hydroxyapatite = Next, 100 g of sodium alginate powder was added to this hydroxyapatite aqueous suspension, and the resulting mixture was A spherical cured product was obtained by dropping it into a 10% by weight aqueous calcium chloride solution at a rate of 8001-11/hr, which was washed with water and dried to obtain a spherical molded product (3 mm in wire diameter) of 2.2 KF. The obtained spherical molded body 10f was crushed, immersed in a 10% aqueous solution of tannic acid, then pulled up and dried to prepare a tannic acid-adsorbed hydroxyapatite sustained release body containing 1 g of tannic acid. The deodorizing power of this sustained release product was tested in the same manner as in Example 1, and the results are shown in Table 1.

Comparative Example 1 Zeolite (Sun Zeolite Kogyo Zeolite 5s) i
A tannic acid adsorbing zeolite was prepared by spraying 2.5 liters of a 40% aqueous solution of tannic acid to the OP, and its deodorizing power was tested in the same manner as in Example 1. The results are shown in Table 1.

Table 1 Example 3 The hydroxyapatite spherical molded body 10F obtained in Example 2 was immersed in a 1096 carbon tetrachloride solution of naphthalene and then pulled out to volatilize the carbon tetrachloride and convert the naphthalene 2F into A sustained-release material containing naphthalene-adsorbed hydroxyapatite was prepared. This sustained release material was placed in a constant temperature bath at a temperature of 40.degree. C., and the change in weight after a certain period of time was measured to determine the remaining percentage of naphthalene to examine sustained release properties. Second result
Shown in the table.

Comparative Example 2 A piece of 10F silica gel (spherical silica gel manufactured by Fuji Davison) was taken, immersed in a 1096 carbon tetrachloride solution of naphthalene, and then pulled up to volatilize carbon tetrachloride to prepare a naphthalene-adsorbing silica gel containing 2 g of naphthalene. did. The sustained release properties were investigated using the same method as in Example 3, and the results are shown in Table 2.

Reference Example 1 Table 2 shows the results of examining weight changes using naphthalene 2f in the same manner as in Example 3.

Table 2 Example 4 Take the hydroxyapatite powder 2Of obtained in Example 1,
51 grams of 2-ether-hexyl-2-cyano-3,3-diphenyl-acrylate (liquid ultraviolet absorber) was added to this to prepare an ultraviolet absorber-adsorbed hydroxyapatite sustained release material. This sustained release material 25F was added to 50 (l) of polypropylene resin (Noblen W101 manufactured by Sumitomo Chemical Co., Ltd.), and molded with an injection molding machine (Model TS-100 manufactured by Nissei Plastics Co., Ltd.) to a
It was made into a disk with a thickness of 2 mm. Using this specimen, AS
The durability of the ultraviolet absorber was determined by conducting a 600-hour accelerated weathering test using a carbon arc weather meter (Toyo Rika Kogyo *) according to the test method of TM-D-1499 and observing the surface condition of the test piece. The results are shown in Table 3.

Comparative Example 3 Calcium carbonate (light calcium carbonate PC manufactured by Shiraishi Kogyo)
) 2-ethyl-hexyl-2-cyano-3,3 to 20f
- 5 g of diphenyl acrylate was added to prepare ultraviolet absorber-adsorbed calcium carbonate, which was added to polypropylene resin, and the durability of the ultraviolet absorber was examined in the same manner as in Example 4. The results are shown in Table 3.

Table 3 Example 5 10 g of the hydroxyapatite spherical molded product obtained in Example 2 was taken, and alkyl polyaminoethylglycine hydrochloride (
A disinfectant-adsorbed hydroxyapatite sustained-release body was prepared by impregnating 2F with a 5% aqueous solution (bactericide).

The bactericidal ability of this sustained release product was tested according to JIS-0101 by the following method.

Take 1,000 ffill of groundwater (Nakamachi, Tsukumi City, Oita Prefecture) and leave it for 10 days, then add the sustained release agent for 5 days.
* K @ * n″oam**+m*t, “・11”
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Comparative Example 4 Silica gel (spherical silica gel manufactured by Fuji Davison) 10F was impregnated with 21 hours of aqueous solution of alkyl polyaminoethylglycine hydrochloride 596 to prepare a disinfectant-adsorbing silica gel, and its disinfectant ability was tested in the same manner as in Example 5. The results are shown in Table 4.

Reference Example 2 Table 4 shows the results of measuring the number of organisms in the same manner as in Example 5 without adding any fungicide.

Table 4 Example 6 10f of the hydroxyapatite spherical molded product obtained in Example 2 was taken, and 1 of piperonyl °butoxide (insect repellent) was added to it.
An insect repellent-adsorbed hydroxyapatite sustained-release material was prepared by impregnating 2 g of 096 aqueous solution, and its insect repellent ability was tested by the following method.

The rice with a slight occurrence of insects was washed with water and dried to make it insect-free, and the sustained-release material (12 g) wrapped in Japanese paper was placed in 10 KfO of this rice and placed in a plastic bag together with the rice. They were stuffed and left for a certain period of time to observe the appearance of insects. The results are shown in Table 5.

Comparative Example 5 Calcium carbonate (light calcium carbonate PC manufactured by Shiraishi Kogyo)
) Prepare insect repellent adsorbed calcium carbonate by impregnating 2f with 1096 aqueous solution of logtz piperonyl butoxide,
Its insect repellent ability was measured in the same manner as in Example 6. The results are shown in Table 5.

201 Example 7 Example 1 + Take 200f of the obtained hydroxyapatite powder and add 209 benzotriazole (volatile rust preventive) to it.
A rust preventive agent-adsorbed hydroxyapatite sustained-release body was prepared by adding the anti-corrosion agent, and a rust prevention test was conducted using the following method.

The controlled release material 220f was placed in the bottom of a decal (without lid) with a diameter of a o o mm, and a rolled steel plate specified by JIS-G-3141 was immersed in 596 saline solution for 5 seconds, then pulled out and dried. It was placed on the shelf of a desiccator and kept in a constant temperature and humidity chamber at a humidity of 65% and a temperature of 30' (:!), and the condition until rust appeared was observed.

The results are shown in Table 6.

Comparative Example 6 Calcium carbonate (calcium carbonate manufactured by Shiraishi Kogyo) 200f
2 Of benzotriazole was added to prepare rust preventive adsorbed calcium carbonate, and the rust prevention test was carried out in the same manner as in Example 7. The results are shown in Table 6.

Reference Example 3: No rust preventive agent adsorbed to hydroxyapatite, except for Example 7
A rust prevention test was conducted in the same manner as above. The results are shown in Table 6.

Table 6 Example 8 Hydroxyapatite powder 1 obtained in Example 1 (taking 1,
2,5-dimethyl-2,5-di(1-butylperoxy)hexane (organic peroxide) was added to this to prepare a peroxide-adsorbed hydroxyapatite sustained release material, and the adsorbed peroxide Changes in quantity over time were measured using the following method to examine sustained release properties.

The sustained release material was kept in an oven at 40° C., and the sustained release property of the sustained release material was determined by determining the change in the amount of adsorbed peroxide by iodometric titration. The results are shown in Table 7.

Comparative Example 7 Calcium carbonate (light calcium carbonate PC manufactured by Shiraishi Kogyo)
) 10y, 2f of 2,5-dimethyl-2,5-di(t-butylperoxy)hexane was added to prepare peroxide-adsorbed calcium carbonate, and the change over time in the amount of adsorbed peroxide was measured in Example 8. Sustained release properties were determined by measuring in the same manner as above. The results are shown in Table 7.

Reference Example 4 The weight change of 2,5-dimethyl-2,5-di(t-butylperoxy)hexane was measured in the same manner as in Example 8. The results are shown in Table 7.

(that's all)

Claims (2)

[Claims] (1) Substances to be released (excluding fragrance) on a base material made of a calcium phosphate compound with Ca/P (molar ratio) = 1.0 to 2.0 and a specific surface area of 50 to 300 m^2/g by BET method. Calcium phosphate-based sustained release product made by adsorbing. (2) The substances to be released are deodorizers, disinfectants, agricultural chemicals, pharmaceuticals, antioxidants, ultraviolet absorbers, taste substances, fungicides, insect repellents,
The calcium phosphate sustained release material according to claim 1, which is at least one of a volatile rust preventive agent, a plant growth regulator, a food preservative, and a peroxide.