Lipid peroxide adsorbent

Abstract

To provide an adsorbent having superior adsorption capacity for lipid peroxides.SOLUTION: An adsorbent of the present invention is a highly crystalline hydroxyapatite having a Ca / P (molar ratio) of 1.6 to 1.8. Preferably, its crystal shape is powder.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to the adsorption of lipid peroxides by hydroxyapatite.

Background Art

[0002] Lipid peroxides have attracted attention for their association with aging and diseases (Non-Patent Document 1, Non-Patent Document 2). On the skin, sebum secreted from sebaceous glands is said to be oxidized by oxygen and ultraviolet rays in the air to become lipid peroxides (Non-Patent Document 3), and 12% of the sebum is squalene (Non-Patent Document 4). Among the lipids contained in sebum, squalene has been found to be the first target of reactive oxygen species, and a lipid peroxidation reaction occurs from squalene (Non-Patent Document 5). The peroxide of squalene exhibits cytotoxicity (Non-Patent Document 6), and the oxidation of lipids contained in skin lipids such as squalene and cosmetics causes skin aging, acne, and rough skin (Non-Patent Document 7). Titanium oxide used in foundations and the like has been found to cause promotion of squalene oxidation (Non-Patent Document 8), and silica excellent in sebum adsorption has been added to cosmetics, but its harmful effects on health (irritation, carcinogenicity, etc.) have been pointed out (Non-Patent Document 9). Therefore, attention has been focused on hydroxyapatite, which is known for its excellent biocompatibility and ability to adsorb lipid peroxides. Hydroxyapatite [Ca 10 (PO4)6(OH)2 or Ca 10-Z (HPO4) Z (PO4) 6-Z (OH) 2-z ·nH2O)] (hereinafter HAP) is a major constituent of human bones and teeth. When implanted in the living body, it has good affinity with the living body and extremely good chemical bonding property with natural bone, so it is used as a material for artificial bones, artificial teeth, etc. It is also used as a column packing material for chromatography by utilizing its good affinity with proteins.

[0003] Patent Document 1 discloses that HAP with low crystallinity exhibits excellent adsorption performance for various substances. However, in the test for evaluating the ability to adsorb lipid peroxides, hexane is used as a solvent, which is significantly different from the conditions of being formulated in cosmetics and actually applied to the skin.

[0004] Patent Document 2 discloses that a cosmetic containing spherical HAP sintered body particles suppresses the gloss and color tone changes that occur over time after application to the skin, but does not mention the amount of lipid peroxide adsorbed by HAP. Also, the more preferable firing temperature is 500 to 1200 °C, which includes the temperature at which OH groups are missing, so sufficient effects cannot be expected.

Prior Art Documents

[0005]

Patent Document 1

Patent Document 2

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Non-Patent Document 7

Non-Patent Document 8

Non - Patent Document 9

Summary of the Invention

Problems to be Solved by the Invention

[0006] Against such a background, it is an object to provide an adsorbent excellent in lipid peroxide adsorption ability by evaluating the lipid peroxide adsorption ability in a method close to the conditions of actually applying to the skin when blended in cosmetics and the like.

Means for Solving the Problems

[0007] The lipid peroxide adsorbent of the present invention is characterized by having excellent lipid peroxide adsorption ability by firing powder HAP.

Effects of the Invention

[0008] The present invention can provide a lipid peroxide adsorbent with high safety and biocompatibility and gentle to the skin.

Modes for Carrying Out the Invention

[0009] It is considered that when the crystallinity is high, the physical and chemical stability is improved, and the adsorption force is improved by determining the crystal plane. Regarding the reason why the powder HAP fired under the above conditions (hereinafter sometimes referred to as fired powder hydroxyapatite or fired powder HAP) can exhibit lipid peroxide adsorption ability, not all of it has been elucidated, but it can probably be considered as follows. That is, it is considered that the crystal structure of HAP is stabilized by the above firing, so that the crystal structure is reconstructed, and the desorption of H2O present on the solid surface, the rearrangement of OH groups, etc. are considered to occur. Also, it is considered that OH groups are desorbed by dehydration at 800 °C or higher, and the lipid peroxide adsorption ability decreases. Furthermore, if the crystallinity is too low or too high, or the BET specific surface area is too low or too high, the adsorption ability decreases, so it is important to control the crystallinity and BET specific surface area.

[0010] As an embodiment, the lipid peroxide adsorbent of the present invention is amorphous powdered HAP (hereinafter referred to as powdered HAP), and is characterized by firing powdered HAP having a Ca / P molar ratio of 1.6 to 1.8 under specific conditions (hereinafter referred to as fired powdered HAP). The firing temperature at this time is preferably 200 to 800°C, more preferably 500 to 800°C, and even more preferably 600 to 700°C. The firing atmosphere at this time is not particularly limited, and either in the air or in an inert atmosphere (for example, nitrogen atmosphere) can be adopted. After the firing, it is pulverized as necessary to obtain a powder having an average particle size of about 1 to 30 μm. The X-ray diffraction analysis result preferably has a half-value width of d = 2.814 Å of 0.2 to 0.6°, more preferably 0.24 to 0.41°, and even more preferably 0.30 to 0.35°. The BET specific surface area is preferably 10 m 2 / g or more, more preferably 20 to 50 m 2 / g, and even more preferably 25 to 40 m 2 / g. The pH of the liquid in which the fired powdered HAP is suspended at 10 wt% is preferably 7 to 12, more preferably 8 to 12, and even more preferably 9 to 12.

[0011] Incidentally, the unfired powdered HAP (hereinafter referred to as unfired powdered HAP), which is the raw material of the fired powdered HAP in the present invention, can be produced by a normal production method (wet method) (see the examples described later), but commercially available products can also be used (for example, "Hydroxyapatite (Quasi-drug Raw Material Standard)": manufactured by Taihei Chemical Industry Co., Ltd.).

[0012] The fired powdered HAP of the present invention can be formulated by being blended into pharmaceuticals, quasi-drugs, cosmetics, etc. For example, it can be added to facial cleansers, foundations, gels, creams, packs, emulsions, lotions, lotions, and powders.

Examples

[0013] Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited by the following examples, and it is of course possible to appropriately modify and implement within the scope that conforms to the gist of the foregoing and following descriptions, and all of them are included in the technical scope of the present invention.

[0014] 〔Method〕 〈Method for Measuring pH〉 HAP was weighed and a 10 wt% suspension was prepared with purified water, and the pH was measured.

[0015] 〈Method for Measuring BET Specific Surface Area〉 The measurement was performed by the BET multi-point method. The pretreatment was carried out with BELPREP VAC II (manufactured by Microtrac BEL). The measurement of the BET specific surface area was performed with BELSORP-mini II (manufactured by Microtrac BEL), and the results of the BET specific surface area were analyzed with BEL Master TM software.

[0016] 〈Method for Measuring Average Particle Size〉 The measurement was performed with MT3300EX II (manufactured by Microtrac BEL) (with ultrasonic treatment).

[0017] 〈Method for Measuring Ca / P Molar Ratio〉 The measurement was performed using an ICP emission spectroscopic analyzer (PS3520VDD II, manufactured by Hitachi High-Tech), and the Ca / P molar ratio was calculated by the calibration curve method.

[0018] 〈Method for Measuring Full Width at Half Maximum〉 The measurement was performed using a powder X-ray diffractometer MiniFlex600-C (manufactured by Rigaku) for crystal structure analysis to obtain the full width at half maximum. The measurement conditions were as follows: X-ray generator: 40 kV, 15 mA, scan speed: 2.00° / min, step width: 0.02°, scan axis: 2θ / θ, scan range: 3 - 80°.

[0019] 〈Method for Evaluating Peroxide Lipid Adsorption Capacity〉 · Preparation of Peroxide Lipid Put 200 g of squalene (reagent grade, peroxide value: 2.3 - 3.6 meq / kg, manufactured by FUJIFILM Wako Pure Chemical Corporation) into a stainless-steel square tray and heat it in a dryer (Constant Temperature Oven SD450, manufactured by Masuda Rika Kogyo) set at 80 °C for 50 hours to produce peroxidized lipid (heated squalene). The peroxide value of the produced peroxidized lipid (heated squalene) was 40 - 60 meq / kg. · Preparation of Samples Put 5 g of HAP and 20 g of heated squalene into a centrifuge tube and disperse the HAP with a vortex mixer (VORTEX―GENIE2, manufactured by MS Instruments). Stir this mixture at 37 °C (constant temperature bath: Constant Temperature Oven DKN812, manufactured by Yamato Scientific) for 2 hours using a mini rotator (MINI ROTATOR ACR―100, manufactured by AS ONE). Then, centrifuge it at 8000 rpm for 15 minutes at 25 °C using a centrifuge (high-speed cooling centrifuge Model 6200, manufactured by Kubota Shoko). Collect the supernatant part into a screw tube and use it as a sample for measuring peroxidized lipid. · Measurement of Peroxidized Lipid The measurement was carried out by the acetic acid - isooctane method. The peroxide value was calculated as the average value of three measurements using the following calculation formula. Peroxide value (meq / kg) = {Volume of 0.01M sodium thiosulfate solution dropped (mL) × 10 × factor} / Amount of oil or fat (g) The peroxidized lipid adsorption amount was calculated by the following calculation formula. Peroxidized lipid adsorption amount per 1 g of HAP (meq / kg) = {(Peroxide value of heated squalene untreated with HAP (meq / kg) - Peroxide value of heated squalene treated with HAP (meq / kg)} / 5

Example

[0020] (Wet method) Calcium hydroxide (reagent special grade, manufactured by FUJIFILM Wako Pure Chemical Corporation) 73.7 g and purified water were added to a stainless-steel beaker to prepare a 10 wt% suspension. This suspension was heated to 50 °C or higher, and 195.1 g of 30 wt% phosphoric acid solution (diluted from reagent special grade, manufactured by FUJIFILM Wako Pure Chemical Corporation) was added dropwise. After the addition was completed, the mixture was left standing for 1 hour to synthesize HAP. After the reaction solution was subjected to solid-liquid separation, it was dried at 150 °C, and the obtained HAP was pulverized and sieved to obtain unfired hydroxyapatite powder (unfired powder HAP). The obtained unfired powder HAP was fired in an electric furnace (KDF Electric Furnace 300-Plus, manufactured by Denken High Dental) in the temperature range of 600 °C to 700 °C as shown in Table 1 below (firing atmosphere: air) to obtain fired powder HAP. The obtained unfired powder HAP and fired powder HAP were confirmed to be hydroxyapatite (JCPDS: 9-432) by X-ray diffraction measurement. Also, the pH, BET specific surface area, average particle size, Ca / P molar ratio, full width at half maximum (FWHM), and amount of peroxide lipid adsorption of the obtained fired powder HAP are shown in Table 1.

[0021]

Table 1

[0022] 〔Comparative Example 1〕 The unfired powder HAP prepared in Example 1 was fired in an electric furnace (KDF Electric Furnace 300-Plus, manufactured by Denken High Dental) in the temperature range of 200 to 800 °C as shown in Table 2 below (firing atmosphere: air) to obtain fired powder HAP. The obtained unfired powder HAP and fired powder HAP were confirmed to be hydroxyapatite (JCPDS: 9-432) by X-ray diffraction measurement. Also, the pH, BET specific surface area, average particle size, Ca / P molar ratio, full width at half maximum (FWHM), and amount of peroxide lipid adsorption of the obtained unfired powder HAP and fired powder HAP are shown in Table 2.

[0023]

Table 2

[0024] [Comparative Example 2] (Wet method / spray drying: Method for producing spherical HAP) 73.7 g of calcium hydroxide (reagent grade, manufactured by Fujifilm Wako Pure Chemical Corporation) and purified water were added to a stainless steel beaker to prepare a 5 wt% suspension. This suspension was heated to 50°C or higher, and 585.3 g of a 10 wt% phosphoric acid solution (diluted from reagent grade, manufactured by Fujifilm Wako Pure Chemical Corporation) was added dropwise. After the addition was completed, the mixture was left standing for 1 hour to synthesize HAP. The reaction solution was spray-dried at 200°C and then subjected to sieving to obtain spherical hydroxyapatite (hereinafter referred to as uncalcined spherical HAP). The obtained uncalcined spherical HAP was calcined at 500°C and 600°C as shown in Table 3 below (calcination atmosphere: air) using an electric furnace (KDF Electric Furnace 300-Plus, manufactured by Denchen High Dental) to obtain calcined spherical HAP. The obtained uncalcined spherical HAP and calcined spherical HAP were confirmed to be hydroxyapatite (JCPDS: 9-432) by X-ray diffraction measurement. Also, the pH, BET specific surface area, average particle size, Ca / P molar ratio, full width at half maximum (FWHM), and peroxide adsorption amount of the obtained uncalcined spherical HAP and calcined spherical HAP are shown in Table 3.

[0025] [Table 3]

[0026] [Comparative Example 3] (Hydrolysis method: Method described in JP-A-2003-126687) 102.8 g of calcium hydrogen phosphate dihydrate (manufactured by Taihei Chemical Industry Co., Ltd.) and 39.9 g of calcium carbonate (reagent grade, manufactured by Fujifilm Wako Pure Chemical Corporation) were added to a stainless-steel beaker, and purified water was added to make a 10 wt% suspension. This suspension was heated and stirred at 90 °C and held for 4 hours to synthesize HAP. After the reaction solution was subjected to solid-liquid separation, it was dried at 150 °C, and the obtained HAP was pulverized and sieved to obtain plate-shaped HAP (unfired plate-shaped HAP-1). The obtained unfired HAP-1 was fired at 600 °C using an electric furnace (KDF Electric Furnace 300-Plus, manufactured by Denken High Dental) (firing atmosphere: air) to obtain fired plate-shaped HAP-1. The obtained unfired plate-shaped HAP-1 and fired plate-shaped HAP-1 were confirmed to be hydroxyapatite (JCPDS: 9-432) by X-ray diffraction measurement. In addition, the pH, BET specific surface area, average particle size, Ca / P molar ratio, full width at half maximum (FWHM), and amount of adsorbed lipid peroxide of the obtained unfired HAP-1 and fired plate-shaped HAP-1 are shown in Table 4.

[0027]

Table 4

[0028] 〔Comparative Example 4〕(Hydrolysis method: production method of JP-A-2003-126687) 102.8 g of calcium hydrogen phosphate dihydrate (manufactured by Taihei Chemical Industry Co., Ltd.) and 29.9 g of calcium carbonate (reagent special grade of Fuji Film Wako Pure Chemical Industries, Ltd.) were added to a stainless-steel beaker, and purified water was added to make a 10 wt% suspension. This suspension was heated and stirred at 90 °C and held for 4 hours to synthesize HAP. After the reaction solution was subjected to solid-liquid separation, it was dried at 150 °C, and the obtained HAP was pulverized and sieved to obtain plate-shaped HAP-2 (unfired plate-shaped HAP-2). The obtained unfired HAP-2 was fired at 500 °C and 600 °C using an electric furnace (KDF Electric Furnace 300-Plus, manufactured by Denken High Dental) (firing atmosphere: air) to obtain fired plate-shaped HAP-2. The obtained unfired plate-shaped HAP-2 and fired plate-shaped HAP-2 were confirmed to be hydroxyapatite (JCPDS: 9-432) by X-ray diffraction measurement. Also, the pH, BET specific surface area, average particle size, Ca / P molar ratio, full width at half maximum (FWHM), and amount of peroxide lipid adsorption of the obtained unfired plate-shaped HAP-2 and fired plate-shaped HAP-2 are shown in Table 5.

[0029]

Table 5

Industrial Applicability

[0030] The fired powder HAP of the present invention can be blended into pharmaceuticals, quasi-drugs, cosmetics, etc., and can be provided in dosage forms such as facial cleansers, foundations, gels, gels, creams, packs, emulsions, lotions, lotions, skin toners, powders, etc. having the ability to adsorb peroxide lipids.

Claims

**Claim 1** A peroxidized lipid adsorbent obtained by firing a powdered hydroxyapatite having a Ca / P molar ratio of 1.6 to 1.

8. **Claim 2** A peroxidized lipid adsorbent obtained by firing the powdered hydroxyapatite according to Claim 1 at 600 to 700°C. **Claim 3** A peroxidized lipid adsorbent having a half-value width of d = 2.814 Å in the X-ray diffraction analysis result of 0.2 to 0.6° as described in any one of Claims 1 to 2. **Claim 4** The lipid peroxide adsorbent according to any one of claims 1 to 3, having a BET specific surface area of 10 m ２ / g or more. **Claim 5** A peroxidized lipid adsorbent having a pH of 7 to 12 in a 10 wt% suspension of the fired hydroxyapatite as described in any one of Claims 1 to 4.

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