JPH10182492A - Petal-like porous base for sustained release body and sustained release body composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject base useful as a carrier capable of controlling the sustained release depending upon kinds of use and medicine, by using specific particles. SOLUTION: This base comprises a calcium phosphate-based compound having a petal-like porous structure composed of calcium carbonate as a nucleus material, has an atomic ratio of Ca/P of <=16.7 and satisfies the equations 0.2<=dx1 <=20(μm), 0.01<=dx2 <=1(μm), 50<=Sw1 <=500(m<2> g), 95<=ω1<=99, 70<=ω2<=95, 1<=α<=5 with the proviso that α=d50 /dx1 , 0<=β<=2 with the proviso that β=(d90 -d10 )/d50 [dx1 is an average particle diameter; d2 is an average pore diameter; Sw1 is a BET specific surface area (m<2> /g); ω1 is a stationary porosity (%) obtained by measurement of an apparent specific volume (mL/g) and calculated by formula I,; ω2 is a pressure porosity (%) under 30kg/cm<2> pressure obtained by packing a specimen to a cylinder, pressurizing, measuring the thickness and calculating an equation of formula II; α is dispersion coefficient; d50 is 50% average particle diameter of particle; β is sharpness D90 and d10 are particle diameter of 90% and 10% of the total of sieve passing side].

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a petal-like porous substrate for sustained-release bodies, which is a calcium phosphate compound having a petal-like porous structure using calcium carbonate as a core material, and a variety of chemicals supported on the substrate. More specifically, the sustained-release composition can be controlled in accordance with various chemicals such as agricultural chemicals, antibacterial agents, deodorants, fragrances, ultraviolet absorbers, etc., and plastic molded articles, synthetic resin films, synthetic resins The present invention relates to a petal-like porous base material for a sustained-release body exhibiting an excellent sustained-release effect for various uses such as fibers and paints, and a sustained-release body composition obtained by supporting a drug on the substrate.

[0002]

2. Description of the Related Art Various methods have heretofore been studied for supporting a drug on various substrates and dispersing the drug from the surface of the substrate. Advantages of using the base material include the ability to control the release of the drug and the improvement of the handling properties because the liquid drug can be made into a solid. What is widely used as a base material is activated carbon, felt, sawdust, zeolite, synthetic silica, alumina, calcium silicate, hydroxyapatite, starch, cellulose acetate, and the like. Agrochemicals such as insect repellents and herbicides, antibacterial agents, deodorants, fragrances, ultraviolet absorbers and the like are generally used.

[0003]

However, it is difficult to sufficiently control the elution of the loaded active ingredient with the conventional base materials as described above. If eluted in a short time, not only will the persistence be reduced, but also a large amount of the drug will act temporarily, causing a problem of phytotoxicity, and conversely, the active ingredient will not be eluted well And almost no effect is recognized. Although the elution of the active ingredient is controlled by increasing or decreasing the amount of the drug carried, sufficient control is not possible only by increasing or decreasing the amount depending on the properties of the drug used. Accordingly, there has been a demand for a sustained-release body which can be freely set depending on the use of the control of the fast-acting action and the slow-acting action and the kind of the drug.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and have found that particles having a specific particle shape, a specific specific surface area and a pore size, a specific particle size and a dispersity, The present inventors have found that a sustained-release body composition comprising a drug supported on the particles has a desired function, and completed the present invention. Hereinafter, the present invention will be described in detail.

A first aspect of the present invention is a calcium phosphate-based compound having a petal-like porous structure using calcium carbonate as a core material, wherein the atomic ratio of Ca / P is 16.7 or less;
And a petal-like porous substrate for a sustained release body, characterized by satisfying the following formulas (a) to (g). (A) 0.2 ≦ dx1 ≦ 20 (μm) (b) 0.01 ≦ dx2 ≦ 1 (μm) (c) 50 ≦ Sw1 ≦ 500 (m ² / g) (d) 95 ≦ ω1 ≦ 99 (e) ) 70 ≦ ω2 ≦ 95 (f) 1 ≦ α ≦ 5, where α = d50 / dx1 (g) 0 ≦ β ≦ 2, where β = (d90−d10) / d
50, where dx1: average particle diameter (μm) of particles measured by electron micrograph. dx2: average pore diameter (μm) of the particles determined by the pore distribution measured by the mercury intrusion method. Sw1: BET specific surface area by nitrogen adsorption method (m ² / g) ω1: JISK5101-91 20.1 Measure the apparent specific volume (ml / g) by the static method of the pigment test method, and calculate by the following formula (h) Calculated static porosity (%) ω2: 0.5 g sample was filled in a cylinder having a cross-sectional area of 2 cm ² , 30
Pressurized at a pressure of kg / cm ² for 30 seconds, the thickness thereof was measured with a vernier caliper, and the pressurized porosity (%) of 30 kg / cm ² calculated from the following formula (i) α: dispersion coefficient d50: 50% average particle diameter (μm) of particles measured by a Microtrac FRA laser type particle size distribution meter. β: sharpness. d90: 90% total particle diameter (μm) of particles passing through the sieve measured by a Microtrac FRA laser type particle size distribution meter. d10: Total 10% particle diameter (μm) of particles passing through a sieve measured by a Microtrac FRA laser type particle size distribution meter.

[0006]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The important feature of the petal-like porous base material for sustained-release body of the present invention is in the form of particles, and it is not a simple calcium phosphate-based compound but a porous calcium phosphate-based compound having a petal-like structure. Is to be. The petal-like porous substrate for sustained-release body of the present invention has a high specific surface area due to its petal-like structure, and has excellent carrying performance, as well as fast-acting and slow-acting controls. It can be set freely according to the type of the medicine or the medicine. The second aspect of the present invention is a sustained-release body composition obtained by supporting various drugs on the petal-like porous base material for sustained-release body, by using the petal-like porous base material for sustained-release body. It is possible to release a drug suitable for various uses. Further, the sustained-release body composition of the present invention is excellent in dispersibility and particle uniformity, so that it can be blended for any use. For example, applications requiring dispersibility and uniformity of particles include synthetic resin films and synthetic resin fibers.
It has powder properties that can be used sufficiently for these applications.

Factors controlling the sustained release are as follows:
The shape and size of the sustained release particles are dependent on the balance between the average pore diameter and the specific surface area of the porous shape. Most of the conventional sustained release bodies also have a porous shape and a high specific surface area, but it is difficult to freely adjust the average pore diameter and the specific surface area, and it is difficult to control the sustained release performance. . The petal-like porous substrate for sustained-release body of the present invention is not simply porous and has a high specific surface area,
It has pores and specific surface areas adjusted according to the active ingredient to be used and the application, and has an unprecedented excellent sustained release performance. Hereinafter, the present invention will be described in detail.

The petal-like porous calcium phosphate compound constituting the petal-like porous base material for sustained-release body of the present invention is not particularly limited, but amorphous calcium phosphate [abbreviation AC]
P, chemical formula Ca ₃ (PO ₄ ) ₂ .nH ₂ O], fluorapatite [abbreviation FAP, chemical formula Ca ₁₀ (PO ₄ )]
₆ F ₂ ], chlorapatite [abbreviation CAP, chemical formula Ca ₁₀
(PO ₄ ) ₆ Cl ₂ ], hydroxyapatite [abbreviation H
AP, chemical formula Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ], octacalcium phosphate [abbreviation OCP, chemical formula Ca ₈ H ₂ (P
O _{4) 6} · 5H ₂ O], tricalcium phosphate [Symbol TC
P, chemical formula Ca ₃ (PO ₄ ) ₂ ], calcium hydrogen phosphate (abbreviation DCP, chemical formula CaHPO ₄ ), calcium hydrogen phosphate dihydrate (abbreviation DCPD, chemical formula CaHPO ₄
2H ₂ O) and the like, and may be one kind or two or more kinds. Among them, hydroxyapatite, octacalcium phosphate, tricalcium phosphate and calcium hydrogenphosphate are preferable from the viewpoint of high stability of the composition, and hydroxyapatite is preferred. Is particularly preferred. As for the content of the hydroxyapatite having the highest stability, the content is preferably 10% by weight or more based on the total calcium phosphate-based compound.
0 wt% is more preferred and 90 wt% is most preferred.

The atomic ratio of Ca / P in the particles of the petal-like porous substrate for sustained-release body of the present invention is 16.7 or less, and from the viewpoint of carrying and releasing the drug efficiently, 5 .
56 or less is preferable, and 3.33 or less is more preferable,
Most preferred is 1.85 or less. The atomic ratio of Ca / P is 1
If it exceeds 6.7, the drug is not sufficiently loaded. The lower limit of the atomic ratio is preferably about 1.60 from the viewpoint of maintaining the stability of the particles. Further, all of the calcium carbonate used as the core material was changed to a calcium phosphate compound, and calcium carbonate as the core material was not present in the particles, and 100% of the particle weight (atomic ratio of Ca / P was 1-1.67). )
There is no problem if is changed to a petal-like porous calcium phosphate compound.

The average particle diameter dx1 of the sustained-release petal-like porous substrate of the present invention is 0.2 ≦ dx1 ≦ 20 (μm), preferably 0.2 ≦ dx1 ≦ 10 (μm), and more preferably. Is 0.5 ≦ dx1 ≦ 5 (μm). . When the average particle diameter is less than 0.2 μm, the particles are significantly aggregated and the sustained release performance is reduced. In addition, when it exceeds 20 μm, for example, the scattering property is reduced when the pesticide is carried and widely spread over the fields and the like, and when all the voids of the particles are filled with the drug, the average particle diameter is defined as the diameter. Is the area of the sphere
The effective area (the area where the drug is diffused) decreases, and the sustained release performance decreases.

The average pore diameter dx2 of the petal-like porous substrate for sustained-release body of the present invention is 0.01 ≦ dx2 ≦ 1 (μm). When the average pore diameter is less than 0.01 μm, the carried drug is not sufficiently dispersed because the pore diameter is small, and the sustained release effect is not exhibited. If it exceeds 1 μm, the carried drug is diffused in a short time because the pore diameter is large,
The sustained release effect is reduced.

The specific surface area Sw1 of the petal-like porous substrate for sustained-release body of the present invention is 50 ≦ Sw1 ≦ 500 (m ² / g), preferably 100 ≦ Sw1 ≦ 400 (m ² / g). is there. When Sw1 is less than 50 m ² / g, good drug loading and sustained release performance cannot be obtained. When Sw1 exceeds 500 m ² / g, loading performance is high, but good divergence of the loaded material is not performed. Good sustained release performance cannot be obtained.

The stationary porosity ω1 and the pressurized porosity ω2 of the petal-like porous substrate for sustained-release body of the present invention are respectively 95 ≦ ω1.
≦ 99, 70 ≦ ω2 ≦ 95. ω1 is less than 95, ω
When 2 is less than 70, the porosity is small, so that the amount of support becomes insufficient. When ω1 exceeds 99 and ω2 exceeds 95, the effective area of the particles having sustained release properties is small, although the amount of the support is sufficient.

The dispersibility α of particles and the uniformity β of particles of the petal-like porous substrate for sustained-release body of the present invention are respectively 1 ≦ α ≦
5, 0 ≦ β ≦ 2, preferably 1 ≦ α ≦ 2, 0 ≦ β
≦ 1. When α exceeds 5, the ratio of coarse aggregates increases, and the effective area of particles having sustained release performance decreases. When α is less than 1, the proportion of fine particles increases, the cohesiveness of the particles increases, and the effective area of the particles having sustained release performance decreases. If β exceeds 2, the particle size is not uniform and the sustained release effect also varies.

The sustained-release composition of the present invention comprises a drug supported on the petal-like porous substrate for a sustained-release body of the present invention. The drug to be supported is not particularly limited, but high sustained-release performance is required. It is preferable to use a pesticide, an antibacterial agent, a deodorant, a fragrance, an ultraviolet absorber, etc., because excellent sustained release performance is exhibited. These are carried alone or in combination of two or more. For example, the following are exemplified for pesticides, antibacterial agents, deodorants, fragrances, and ultraviolet absorbers. (Agricultural chemicals) Organophosphorus pesticides such as isoxathion, diazinon, pyraclophos, disulfotone, prothiophos, etc., carbofuran pesticides such as carbosurphan, furatiocarb, carbofuran, etc., pyrethroid pesticides such as allethrin, flucitrinate, tefluthrin and aldrin, Chlorinated insecticides such as DCIP and heptachlor; herbicide components such as pretilachlor, metolachlor and benthiocarb; (antibacterial agents) quaternary ammoniums such as benzalkonium chloride and cetylpyridinium chloride; Aldehydes such as glyoxal, phenols such as cresol and xylenol, carboxylic acids such as sorbic acid and benzoic acid, and guanidines such as chlorhexidine and n-dodecylguanidine acetate. 2-mercaptobenzothiazole, 2
Thiazoles such as -methyl-4-isothiazolin-3-one, (1,4) -2-amino-2-deoxy-β-D
-Chitosans such as glucan, N-carboxymethyl chitosan, glycol chitosan, phosphorylated chitosan, chitosan-2, 5-anhydromannose (deodorants) tannic acid, turpentine oil, show brain oil, and natural fulvic acid (fragrance) Natural flavors such as incense, avies oil, bergamot oil, borogam oil, rosewood oil, rosemary oil, etc., synthetic flavors such as ethyl acetoacetate, anethole, amylcinamic aldehyde, ethyl isovalerate, isoamyl acetate, rose oil, jasmine -Based and lira-based compounded fragrances (UV absorber) 2-ethylhexyl-2-cyano-
3,3-diphenyl acrylate, 2,4-dihydroxybenzophenone, phenyl salicylate, 2- (2 ′
-Hydroxy-5'-methyl-phenyl) -benzotriazole

The method for preparing the petal-like porous substrate for sustained-release body of the present invention is not particularly limited. For example, in a water system in which calcium carbonate is dispersed, water-soluble phosphoric acid or water-soluble phosphate is mixed. Is gradually reacted to produce a petal-like porous calcium phosphate compound on the surface of the core material. Specifically, an aqueous suspension dispersion of calcium carbonate serving as a specific core material and a diluted aqueous solution of phosphoric acid and / or an aqueous suspension dispersion of a specific calcium dihydrogen phosphate and / or a specific calcium hydrogen phosphate 2 An example is a method in which an aqueous suspension dispersion of a water salt is mixed at a specific ratio under specific mixing conditions, aged under specific aging conditions, and then dried.

The method of preparing a calcium phosphate-based compound having a petal-like porous structure for sustained-release according to the present invention, which is mainly composed of a petal-like porous hydroxyapatite which can be particularly preferably used, will be described below. Specific examples will be described.

A particle size distribution analyzer (S made by Shimadzu Corporation)
A-CP3) has an average particle diameter of 0.1 to 5 μm
m is an aqueous suspension dispersion of calcium carbonate and a diluted aqueous solution of phosphoric acid and / or an average particle diameter measured by a particle size distribution analyzer (SA-CP3 manufactured by Shimadzu Corporation) is 2 to 10.
μm aqueous suspension of calcium dihydrogen phosphate and / or a particle size distribution analyzer (SA- manufactured by Shimadzu Corporation)
An aqueous suspension dispersion of calcium hydrogen phosphate dihydrate having an average particle size of 2 to 10 μm as measured by CP3) was treated with Ca
After mixing in water at an atomic ratio of 16.0 to 1.6.7 under the following mixing conditions, aging is further performed under the following aging conditions, followed by dehydration and water washing, and a dry atmosphere of 300 ° C. or less. Dry underneath and finish crushing.

Mixing conditions Calcium carbonate aqueous suspension dispersion solids concentration 1 to 15
% Concentration of diluted aqueous solution of phosphoric acid 1 to 50% Mixing time 0.1 to 150 hours Mixing system water suspension temperature 0 to 80 ° C Mixing system water suspension pH 5 to 9 Mixing stirring blade peripheral speed 0.5 to Aging condition Ca concentration of aging system 0.4-5% Aging time 0.1-100 hours Aging water suspension temperature 20-80 ° C Aging water suspension pH 6-9 Peripheral speed of stirring blade 0.5-50m / sec

The petal-like porous substrate for a sustained-release body of the present invention comprises a coupling agent such as a silane coupling agent or a titanate coupling agent, an organic acid, For example, α, β monoethylenically unsaturated carboxylic acids and esters thereof such as fatty acids, resin acids, and acrylic acids; organic acids such as oxalic acid and citric acid; inorganic acids such as tartaric acid and hydrofluoric acid; Surface treatment agents such as polymers, salts thereof, or esters thereof, surfactants and condensed phosphoric acids such as sodium hexametaphosphate, pyrophosphate, sodium pyrophosphate, tripolyphosphate, sodium tripolyphosphate, trimetaphosphate, and high polyphosphate. And its salts and the like may be added or surface-treated according to a conventional method.

The method for supporting the various agents on the petal-like porous substrate for sustained release of the present invention is not particularly limited, and a conventional method may be used. For example, the following method can be mentioned. (A) A drug is added to the resulting aqueous suspension of the petal-like porous substrate for sustained-release body to make it into powder. (B) To a powder of a petal-like porous substrate for sustained-release body, a solution obtained by dissolving a drug in a solvent is added by spraying.
(C) A petal-like porous substrate for sustained-release body is immersed in a solution in which a drug is dissolved in a solvent.

The other components to be added to the sustained-release composition of the present invention are not particularly limited. If necessary, inorganic particles such as calcium carbonate, synthetic silica, and calcium silicate may be used alone or according to the purpose. Amorphous calcium phosphate [ACP, chemical formula Ca ₃ (PO ₄ ) _2.
2 O], fluorapatite [abbreviation FAP, chemical formula Ca ₁₀
(PO ₄ ) ₆ F ₂ ], chlorapatite [abbreviation CAP, chemical formula Ca ₁₀ (PO ₄ ) ₆ Cl ₂ ], hydroxyapatite [abbreviation HAP, chemical formula Ca ₁₀ (PO ₄ ) ₆ (O
H) ₂ ], octacalcium phosphate [abbreviation OCP, chemical formula C
_{a 8 H 2 (PO 4)} 6 · 5H 2 O ], tricalcium phosphate [Symbol TCP, chemical formula Ca ₃ (PO _{4) 2],} calcium hydrogen phosphate (abbreviation DCP, formula CaHPO _4),
Calcium hydrogen phosphate dihydrate different from (abbreviation DCPD, formula CaHPO ₄ · 2H ₂ O) sustained-body petaloid porous substrate of the present invention, such as the purpose of petal-like structure having no calcium phosphate compound One or two or more may be added depending on the case.

[0023]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Method for preparing aqueous dispersions a and b of calcium carbonate to be used. Preparation of aqueous suspension dispersion a of calcium carbonate: specific gravity 1.0
At 55, 7000 liters of lime milk (aqueous suspension of calcium hydroxide) at a temperature of 8 ° C. was passed through a furnace gas having a carbon dioxide concentration of 27% by weight at a flow rate of 24 m ³ to carry out a carbonation reaction to pH 9, followed by 40 By carrying out stirring and aging at 時間 50 ° C. for 5 hours, alkalis between the particles are eluted and dispersed to pH 10.8, and the average particle diameter measured from an electron micrograph is 0.05
μm particle size distribution analyzer (SA-C manufactured by Shimadzu Corporation)
An aqueous suspension dispersion of calcium carbonate having an average particle diameter measured by P3) of 0.48 μm was prepared. Preparation of aqueous suspension dispersion b of calcium carbonate: heavy calcium carbonate "Super SS" manufactured by Maruo Calcium Co., Ltd.
(1.2 m ² / g), mixed with water, stirred and dispersed with a TK homomixer (5000 rpm, 15 minutes), and measured for particle size distribution at an average particle size of 3 μm measured from an electron micrograph at a solid concentration of 25%. Container (SA- manufactured by Shimadzu Corporation)
An aqueous suspension dispersion b of calcium carbonate having an average particle size of 3.4 μm as measured by CP3) was prepared.

Examples 1 to 6 and Comparative Examples 1 to 3 According to the raw materials and mixing conditions described in Tables 1 and 2, a stainless steel tank with a baffle plate and a 0.4 m turbine blade having a diameter of 0.6 m with a stirrer were used. ⁽³⁾ An aqueous suspension of calcium carbonate whose concentration was adjusted and whose temperature was adjusted was put into a stainless steel tank, and a diluted aqueous solution of phosphoric acid was dropped and mixed with stirring, and the mixture was aged while stirring under the described aging conditions. After ripening, the solid content concentration is adjusted to 8%, and spray-drying is performed to thereby provide a petal-like porous substrate D1 for a sustained-release body which is a calcium phosphate-based compound having a petal-like porous structure using calcium carbonate as a core material. -D6 and E1-E3 were prepared.
The total weight of the raw material and water was 400 kg. The spray-drying conditions were as follows: spraying particle diameter: about 0.1 mm; hot air temperature at the entrance: 250 ° C .; drying time: about 10 seconds; drying loss immediately after drying at 200 ° C. for 2 hours: 5-8%. Was. Tables 3 and 4 show powder physical properties of the petal-like porous base materials D1 to D6 for sustained release bodies prepared in Examples 1 to 6 and E1 to E3 prepared in Comparative Examples 1 to 3. From Table 3, it can be confirmed that the petal-like porous substrate for sustained-release body of the present invention can freely adjust the specific surface area, the pore diameter and the particle diameter, and has excellent dispersibility and uniform particle diameter. Electron micrographs showing the particle structure of D1 are shown in FIGS. 1 (1000 ×) and 2 (10000 ×).
From FIGS. 1 and 2, it can be confirmed that the petal-like porous substrate for sustained-release body of the present invention has a petal-like structure. D1, D
The powder X-ray diffraction diagrams of D3 and D5 are shown in FIGS. From the results of the powder X-ray diffraction shown in FIGS. 5 and 6, D1 and D2 were not recognized except for the calcium phosphate compound and calcium carbonate (calcite). It can be confirmed that the main component of the calcium phosphate compound is hydroxyapatite (HAP) and contains a trace amount of octacalcium phosphate (OCP). As for D3, calcium carbonate was not recognized from FIG. 7, and no compounds other than the calcium phosphate compound were recognized. It can be confirmed that the main component of the calcium phosphate compound is hydroxyapatite (HAP) and contains a trace amount of octacalcium phosphate (OCP). For comparison with the petal-like porous substrate for sustained-release body of the present invention, electron micrographs showing the particle structure of commercially available hydroxyapatite described below are shown in FIGS.
FIG. 8 shows the powder X-ray diffraction pattern. FIG.
From FIG. 4, it can be confirmed that commercially available hydroxyapatite is fine particles and aggregates of the particles, and does not have a petal-like porous structure. From FIG. 8, it can be confirmed that commercially available hydroxyapatite contains a trace amount of calcium hydrogen phosphate dihydrate (DCPD) in addition to the main component hydroxyapatite (HAP).

[0026]

[Table 1]

[0027]

[Table 2]

[0028]

[Table 3] * 1 ・ ・ ・ Particles corresponding to Examples 1 to 6

[0029]

[Table 4] * Particles corresponding to Comparative Examples 1-3

Examples 7 to 12 Comparative Examples 4 to 9 Petal-like porous substrates D1 to D6 for sustained release of the present invention prepared in Examples 1 to 6, E1 to E3 prepared in Comparative Examples 1 to 3, and Commercially available hydroxyapatite (trade name: tricalcium phosphate, manufactured by Yoneyama Chemical Industry Co., Ltd.), synthetic silica (trade name: Aerosil # 130, manufactured by Nippon Aerosil Co., Ltd.)
5 g each of calcium silicate (trade name: Florite R, manufactured by Tokuyama Soda Co., Ltd.) and 10 g of naphthalene
After immersion in a 4% carbon tetrachloride solution, the carbon tetrachloride was volatilized to obtain a sustained-release composition supporting 2 g of naphthalene.
In order to confirm the sustained-release properties of these sustained-release body compositions, the compositions were placed in a thermostat at a temperature of 30 ° C., and the residual ratio of naphthalene was measured from the weight change after a certain period of time. Table 5 shows powder properties of commercially available hydroxyapatite, synthetic silica, and calcium silicate. Table 6 shows the measurement results of the residual ratio of naphthalene. From Table 6, it can be seen that the sustained release composition of the present invention can control the sustained release by using the petal-like porous substrate for sustained release of the present invention, and has excellent sustainability. You can check.

[0031]

[Table 5]

[0032]

[Table 6]

Examples of the sustained-release composition of the present invention in which pesticides, antibacterial agents, deodorants, fragrances, and ultraviolet absorbers are used as various agents are described below.

Examples 13 to 18 Comparative Examples 10 to 15 Petal-like porous substrates D1 to D6 for sustained release of the present invention prepared in Examples 1 to 6, E1 to E3 prepared in Comparative Examples 1 to 3,
Using commercially available hydroxyapatite, synthetic silica, and calcium silicate as carriers, pyraclofos, a soil insecticidal component, was mixed with a mixer to obtain a sustained-release composition containing 5% by weight of pyraclophos for each carrier. The effects of these sustained-release bodies were confirmed by the following test methods. Table 7 shows the results. From Table 7, it can be confirmed that the sustained release versus composition of the present invention has a highly persistent insecticidal effect. (Test method) Target plant: Tomato Target pest: Sweet potato nematode Test scale: 400 cm ² Addition amount: 3 mg / cm ² Measurement method: Check root condition 30 days after sample addition

[0035]

[Table 7] (Evaluation criteria) A: many roots can be confirmed B: several roots can be confirmed C: roots can hardly be confirmed

Examples 19 to 30 Comparative Examples 16 to 27 Petal-like porous substrates D1 to D6 for sustained release of the present invention prepared in Examples 1 to 6, E1 to E3 prepared in Comparative Examples 1 to 3,
And commercially available hydroxyapatite, synthetic silica, and 10 g each of calcium silicate as a carrier, 2-mercaptobenzothiazole and chitosan-2,5-anhydromannose are spray-added, and 2-mercaptobenzothiazole and A sustained-release composition containing 5% by weight of chitosan-2,5-anhydromannose was obtained. The antibacterial effect of these sustained-release bodies was confirmed by the following method. Table 8 shows the results. From Table 8, it can be confirmed that the sustained-release body composition of the present invention has an excellent antibacterial effect. (Test Method) SCDLP agar medium (for bacteria) manufactured by Nippon Pharmaceutical Co., Ltd. was dissolved, and medium 1 to which 3 ml of sewage containing general germs was added per 100 ml of lysis medium while keeping the temperature at 45 ° C.
A predetermined amount of each of the above Examples and Comparative Examples is added to 0 ml, and the mixture is stirred well. This is put in a petri dish, and after the medium has hardened, the culture is performed with the lid turned upside down. Culture conditions are 30
℃ 5 days.

[0037]

[Table 8]

Examples 31 to 36 Comparative Examples 28 to 33 Petal-like porous substrates D1 to D6 for sustained release of the present invention prepared in Examples 1 to 6, E1 to E3 prepared in Comparative Examples 1 to 3,
Using 10 g of each of commercially available hydroxyapatite, synthetic silica, and calcium silicate as carriers, 5 g of a 40% aqueous solution of a deodorant (tannic acid) was added by spraying to obtain a sustained-release body composition supporting 2 g of tannic acid. . In order to confirm the deodorizing performance of these sustained-release bodies, the nitrogen gas was flowed at 500 ml / min from one of the air-washing bottles (capacity 3000 ml) containing 10% ammonia water at 500 ml / min, and the deodorization was performed at the other outlet. A column filled with the agent was attached, and ammonia passing through the column was introduced into a hydrochloric acid aqueous solution of pH 4, and the time until the deodorizing ability of the sustained-release body composition was reduced and ammonia was not deodorized was adjusted to pH 10 or more. It was determined as time until it was, and the deodorizing ability was examined. Table 9 shows the results. From Table 9, it can be confirmed that the sustained-release body composition of the present invention has excellent and persistent deodorizing performance.

[0039]

[Table 9]

Examples 37 to 42 Comparative Examples 34 to 39 Petal-like porous substrates D1 to D6 for sustained release of the present invention prepared in Examples 1 to 6, E1 to E3 prepared in Comparative Examples 1 to 3,
Further, a perfume (ethyl acetoacetate) was impregnated with 6 g of each of commercially available hydroxyapatite, synthetic silica and calcium silicate as a carrier for 2 hours to obtain a sustained-release composition carrying the perfume. In order to confirm the aroma performance of these sustained-release bodies, they were left in a room at room temperature, and their persistence was measured. Table 10 shows the results. From Table 10, it can be confirmed that the sustained-release body composition of the present invention has excellent and long lasting aroma performance.

[0041]

[Table 10] (Evaluation criteria) A: Almost no decrease in fragrance B: Slightly decrease in fragrance C: Half of fragrance D: Little fragrance

Examples 43 to 48 Comparative Examples 40 to 45 Petal-like porous substrates D1 to D6 for sustained release of the present invention prepared in Examples 1 to 6, E1 to E3 prepared in Comparative Examples 1 to 3,
And a sustained-release composition containing 25 g of each of commercially available hydroxyapatite, synthetic silica and calcium silicate, and adding 5 g of 2-ethylhexyl-2-cyano-3,3-diphenylacrylate to carry an ultraviolet absorber. I got In order to confirm the ultraviolet absorption performance of these sustained-release bodies, a blend of 30 g of the sustained-release bodies and 500 g of polypropylene resin pellets was kneaded with a kneading extruder to obtain polypropylene resin pellets containing the sustained-release bodies. The pellet was obtained by injection molding to obtain a polypropylene molded product. ASTM-D-14 using this molded product
According to the test method No. 99, an accelerated weather resistance test was conducted for 600 hours using a carbon arc type weather meter, and the surface condition of the molded article was examined. Table 11 shows the results. From Table 11, it can be confirmed that the sustained release versus composition of the present invention has a highly persistent ultraviolet absorbing effect.

[0043]

[Table 11] (Surface condition evaluation criteria) A: No change B: Some cracks C: Many cracks

[0044]

As described above, the petal-like porous substrate for sustained-release body of the present invention having a specific particle shape, a specific pore size and a specific surface area, a specific particle size and a specific degree of dispersion, is used depending on the application. The controlled release property can be controlled, and the controlled release composition of the present invention in which the drug is carried on the base material exhibits a controlled release effect excellent for various uses.

[Brief description of the drawings]

FIG. 1 is an electron micrograph (× 1000) showing a particle structure of a particle D1 obtained in Example 1.

FIG. 2 is an electron micrograph (× 10000) showing the particle structure of particle D1 obtained in Example 1.

FIG. 3 is an electron micrograph (× 1000) showing the particle structure of commercially available hydroxyapatite.

FIG. 4 is an electron micrograph (× 10000) showing the particle structure of commercially available hydroxyapatite.

FIG. 5 is a powder X-ray diffraction diagram of a particle D1 obtained in Example 1.

FIG. 6 is an X-ray powder diffraction diagram of a particle D3 obtained in Example 3.

FIG. 7 is a powder X-ray diffraction diagram of a particle D5 obtained in Example 5.

FIG. 8 is a powder X-ray diffraction diagram of a commercially available hydroxyapatite.

Claims (11)

[Claims] 1. A petal-like calcium phosphate compound having a petal-like porous structure containing calcium carbonate as a core material,
A petal-like porous substrate for a sustained-release body, wherein the atomic ratio of a / P is 16.7 or less and the following formulas (a) to (g) are satisfied. (A) 0.2 ≦ dx1 ≦ 20 (μm) (b) 0.01 ≦ dx2 ≦ 1 (μm) (c) 50 ≦ Sw1 ≦ 500 (m ² / g) (d) 95 ≦ ω1 ≦ 99 (e) ) 70 ≦ ω2 ≦ 95 (f) 1 ≦ α ≦ 5, where α = d50 / dx1 (g) 0 ≦ β ≦ 2, where β = (d90−d10) / d
50, where dx1: average particle diameter (μm) of particles measured by electron micrograph. dx2: average pore diameter (μm) of the particles determined by the pore distribution measured by the mercury intrusion method. Sw1: BET specific surface area by nitrogen adsorption method (m ² / g) ω1: JISK5101-91 20.1 Measure the apparent specific volume (ml / g) by the static method of the pigment test method, and calculate by the following formula (h) Calculated static porosity (%) ω2: 0.5 g sample was filled in a cylinder having a cross-sectional area of 2 cm ² , 30
Pressurized at a pressure of kg / cm ² for 30 seconds, the thickness thereof was measured with a vernier caliper, and the pressurized porosity (%) of 30 kg / cm ² calculated from the following formula (i) α: dispersion coefficient d50: 50% average particle diameter (μm) of particles measured by a Microtrac FRA laser type particle size distribution meter. β: sharpness. d90: 90% total particle diameter (μm) of particles passing through the sieve measured by a Microtrac FRA laser type particle size distribution meter. d10: Total 10% particle diameter (μm) of particles passing through a sieve measured by a Microtrac FRA laser type particle size distribution meter. 2. The petal-like porous substrate for a sustained-release body according to claim 1, wherein the average particle diameter dx1 satisfies the following expression (j). (J) 0.2 ≦ dx1 ≦ 10 (μm) 3. The petal-like porous substrate for a sustained-release body according to claim 2, wherein the average particle diameter dx1 satisfies the following expression (k). (K) 0.5 ≦ dx1 ≦ 5 (μm) 4. The BET specific surface area Sw1 is expressed by the following formula (1).
The petal-like porous substrate for a sustained-release body according to any one of claims 1 to 3, which satisfies the following. (L) 100 ≦ Sw1 ≦ 400 (m ² / g) 5. The petal-like porous substrate for a sustained-release body according to claim 1, wherein the dispersion coefficient α and the sharpness β simultaneously satisfy the following expressions (m) and (n). (M) 1 ≦ α ≦ 2 (n) 0 ≦ β ≦ 1.0 6. The petal-like porous substrate for a sustained-release body according to claim 1, wherein the atomic ratio of Ca / P to the weight of the particles is 5.56 or less. 7. The petal-like porous substrate for sustained-release body according to claim 6, wherein the atomic ratio of Ca / P to the particle weight is 3.33 or less. 8. The petal-like porous substrate for a sustained-release body according to claim 7, wherein the atomic ratio of Ca / P to the particle weight is 1.85 or less. 9. The petal-like porous material for a sustained-release body according to claim 1, wherein the petal-like porous calcium phosphate compound is hydroxyapatite having a chemical formula of Ca ₁₀ (PO ₄ ) ₆ (OH) _2. Quality substrate. 10. A sustained release composition comprising a petal-like porous substrate for sustained release according to any one of claims 1 to 9 carrying a drug. 11. The sustained-release composition according to claim 10, wherein the drug is at least one selected from the group consisting of pesticides, antibacterial agents, deodorants, fragrances, and ultraviolet absorbers.