U.S. patent application number 16/665582 was filed with the patent office on 2020-02-27 for hydroxyapatite, cosmetic, food, and method for producing the same.
The applicant listed for this patent is Brainy Inc.. Invention is credited to Hideki Aoki, Nobukiyo Tanaka.
Application Number | 20200060950 16/665582 |
Document ID | / |
Family ID | 63918927 |
Filed Date | 2020-02-27 |
United States Patent
Application |
20200060950 |
Kind Code |
A1 |
Aoki; Hideki ; et
al. |
February 27, 2020 |
HYDROXYAPATITE, COSMETIC, FOOD, AND METHOD FOR PRODUCING THE
SAME
Abstract
According to the present invention, provided is a carbonate- and
magnesium-substituted hydroxyapatite having a particle size of 5 nm
or more and 60 nm or less, wherein a portion of the calcium atoms
in the hydroxyapatite are substituted with magnesium atoms and a
portion of phosphate groups are substituted with carbonate
groups.
Inventors: |
Aoki; Hideki; (Tokyo,
JP) ; Tanaka; Nobukiyo; (Urasoe, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Brainy Inc. |
Naha |
|
JP |
|
|
Family ID: |
63918927 |
Appl. No.: |
16/665582 |
Filed: |
October 28, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
PCT/JP2017/016855 |
Apr 27, 2017 |
|
|
|
16665582 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 8/0241 20130101;
C01B 32/60 20170801; A23L 2/52 20130101; A61K 2800/413 20130101;
C01P 2002/70 20130101; A61K 8/24 20130101; C01B 25/32 20130101;
C01P 2006/12 20130101; A61Q 5/02 20130101; A23C 9/1522 20130101;
A23V 2002/00 20130101; A61Q 19/10 20130101; A61Q 5/12 20130101;
A23L 33/16 20160801; A61K 8/04 20130101; A23C 9/1322 20130101; A61Q
19/00 20130101; C01B 25/322 20130101; C01P 2002/82 20130101; C01P
2004/61 20130101; A23L 2/02 20130101; C01P 2004/64 20130101; C01B
25/16 20130101; A61Q 11/00 20130101; C01P 2002/50 20130101; A23V
2002/00 20130101; A23V 2200/02 20130101; A23V 2250/1578 20130101;
A23V 2250/161 20130101; A23V 2250/1618 20130101 |
International
Class: |
A61K 8/24 20060101
A61K008/24; A61K 8/04 20060101 A61K008/04; A61Q 19/00 20060101
A61Q019/00; A61Q 19/10 20060101 A61Q019/10; C01B 25/16 20060101
C01B025/16; A23L 33/16 20060101 A23L033/16; A23C 9/13 20060101
A23C009/13; A23L 2/02 20060101 A23L002/02; A23L 2/52 20060101
A23L002/52 |
Claims
1. Carbonate- and magnesium-substituted hydroxyapatite having a
part of calcium substituted with magnesium and a part of a
phosphate group substituted with a carbonate group, and being
composed of primary particles in a non-aggregated state, the
primary particles having a particle size of 5 nm or more and 60 nm
or less.
2. The carbonate- and magnesium-substituted hydroxyapatite of claim
1, having the particle size of 10 nm or more and 50 nm or less.
3. The carbonate- and magnesium-substituted hydroxyapatite of claim
1, present in a liquid.
4. The carbonate- and magnesium-substituted hydroxyapatite of claim
1, having a chemical formula
Ca.sub.10-xMg.sub.x(PO.sub.4).sub.6-2/3y(CO.sub.3).sub.y(OH).sub.2,
where x is any value from 0.005 to 0.5, and y is any value from
0.01 to 3.0.
5. The carbonate- and magnesium-substituted hydroxyapatite of claim
1, wherein calcium of the hydroxyapatite is substituted with 0.03
wt % or more and 5 wt % or less of magnesium with respect to
calcium, and a part of the phosphate group is substituted with 0.2
wt % or more and 10 wt % or less of the carbonate group with
respect to the phosphate group.
6. A cosmetic containing the carbonate- and magnesium-substituted
hydroxyapatite of claim 1.
7. The cosmetic of claim 6, containing the carbonate- and the
magnesium-substituted hydroxyapatite at a concentration of 0.001 wt
% or more and 15 wt % or less.
8. The cosmetic of claim 6, wherein the cosmetic is hair shampoo,
rinse, conditioner, treatment, rinse-in shampoo, body shampoo, hand
shampoo, facial cleansing foam, cleansing milky lotion, cleansing
cream, cleansing oil, soap, liquid soap, liquid bath agent, lotion,
cosmetic liquid, cosmetic oil, milky lotion, cream, gel, toothpaste
powder, toothpaste, mouthwash, whitening liquid or deodorant.
9. A food containing the carbonate- and magnesium-substituted
hydroxyapatite of claim 1.
10. The food of claim 9, containing the carbonate- and the
magnesium-substituted hydroxyapatite at a concentration of 0.001 wt
% or more and 15 wt % or less.
11. The food of claim 9, wherein the food is a beverage, dairy
product, edible oil, seasoning, ice cream, soup, cooked food, pet
food or supplement.
12. A method for producing carbonate- and magnesium-substituted
hydroxyapatite having a part of calcium substituted with magnesium
and a part of phosphate group substituted with a carbonate group,
and being composed of primary particles in a non-aggregated state,
the primary particles having a particle size of 5 nm or more and 60
nm or less, the method comprising: preparing a mixed suspension
containing magnesium hydroxide and calcium hydroxide; preparing a
phosphoric acid aqueous solution; and mixing the mixed suspension
and the phosphoric acid aqueous solution in the presence of carbon
dioxide gas or carbonate, causing a neutralization reaction, and
obtaining a suspension containing the carbonate- and
magnesium-substituted hydroxyapatite composed of the primary
particles in the non-aggregated state.
13. A method for producing carbonate- and magnesium-substituted
hydroxyapatite having a part of calcium substituted with magnesium
and a part of phosphate group substituted with a carbonate group,
and being composed of primary particles in a non-aggregated state,
the primary particles having a particle size of 5 nm or more and 60
nm or less, the method comprising: preparing a first solution
containing magnesium salt and calcium salt; preparing a second
solution containing phosphate salt; and mixing the first solution
and the second solution in the presence of carbon dioxide gas or
carbonate, causing a reaction, and obtaining a suspension
containing the carbonate- and magnesium-substituted hydroxyapatite
composed of the primary particles in the non-aggregated state.
14. A method for producing a cosmetic containing carbonate- and
magnesium-substituted hydroxyapatite having a portion of calcium
substituted with magnesium and a portion of phosphate groups
substituted with a carbonate group, and being composed of primary
particles in a non-aggregated stated, the primary particles having
a particle size of 5 nm or more and 60 nm or less, the method
comprising: obtaining a suspension containing the carbonate- and
magnesium-substituted hydroxyapatite by the method of claim 12; and
containing the suspension in the cosmetic.
15. A method for producing a food containing carbonate- and
magnesium-substituted hydroxyapatite having a portion of calcium
substituted with magnesium and a portion of phosphate groups
substituted with a carbonate group, and being composed of primary
particles in a non-aggregated stated, the primary particles having
a particle size of 5 nm or more and 60 nm or less, the method
comprising: obtaining a suspension containing the carbonate- and
magnesium-substituted hydroxyapatite by the method of claim 12; and
containing the suspension in the food.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Continuation Application of PCT
Application No. PCT/JP2017/016855, filed Apr. 27, 2017, the entire
contents of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
[0002] The present invention relates to hydroxyapatite, cosmetic
and food, and a method for producing the same.
2. Description of the Related Art
[0003] Hydroxyapatite (Ca.sub.10(PO.sub.4).sub.6(OH).sub.2) is a
weak alkaline calcium phosphate compound. Hydroxyapatite is used
for artificial bones, artificial tooth roots, bone fillers,
pharmaceutical carriers and the like because of its excellent
biocompatibility. In recent years, hydroxyapatite has also been
applied to cosmetics, foods and the like.
[0004] For example, a technique relating to a liquid or creamy
cosmetic in which a hydroxyapatite colloidal fine particle solid
having a particle size of 0.1 to 0.2 .mu.m is dispersed in water or
an organic solvent is disclosed in Patent Literature 1 (JP
S62-195317 A).
[0005] In addition, a technique of producing a cosmetic containing
2 to 20 .mu.m hydroxyapatite obtained by reacting calcium hydroxide
and an aqueous phosphoric acid solution under alkaline conditions
of pH 10 and drying the aqueous solution with a spray dryer is
disclosed in Patent Literature 2 (JP S63-096110 A).
[0006] Furthermore, a technique relating to magnesium-substituted
crystalline hydroxyapatite with a stable and pure phase that
contains approximately 2.0 to 29% magnesium and at least 75 wt % of
the magnesium is replaced with calcium ions in the hydroxyapatite
lattice structure, is disclosed in Patent Literature 3 (JP
2004-532172 A).
[0007] Moreover, a technique for synthesizing carbonate- and
magnesium-substituted hydroxyapatite containing 0.028 to 0.826 wt %
of magnesium and 0 to 6.83 wt % of carbonate ions is disclosed in
Non-Patent Literature 1 (Materials Research. 2013; 16(4):
779-784).
BRIEF SUMMARY OF THE INVENTION
[0008] However, in the cosmetic producing process, a solution
containing hydroxyapatite of primary particles is dried with a
spray dryer or the like and hydroxyapatite is thereby aggregated
and solidified to form large secondary particles. Since the density
of hydroxyapatite is generally as high as 3.16 g/cm.sup.3, such
hydroxyapatite tends to precipitate and does not disperse uniformly
when added to cosmetics. For this reason, the cosmetic ingredients
composition becomes various. Moreover, such hydroxyapatite is
inferior in the adsorptivity on a lipid, protein, dirt, etc., and
bioaffinity and absorptivity.
[0009] In addition, according to Patent Literature 3,
hydroxyapatite containing approximately 2.0 to 29% magnesium is
magnesium hydroxyapatite, and is different in physical and chemical
properties from calcium hydroxyapatite having high
biocompatibility. The ionic radius of magnesium is as small as
approximately 70% of the ionic radius of calcium. For this reason,
if the amount of magnesium contained in hydroxyapatite
significantly exceeds 2 wt %, it is presumed that the crystal
structure of hydroxyapatite may be distorted, the original
properties of hydroxyapatite may be impaired, and bioaffinity may
be adversely affected.
[0010] Furthermore, according to Non-Patent Literature 1, the size
of the produced hydroxyapatite particles is as large as 63 to 90
.mu.m.
[0011] The present invention has been accomplished in view of the
above circumstances, and its object is to provide hydroxyapatite
with improved bioaffinity, dispersibility, adsorptivity,
absorptivity and cell activation ability, cosmetic and food
containing the same, and a method for producing the same.
[0012] According to the present invention, there is provided
carbonate- and magnesium-substituted hydroxyapatite having a part
of calcium of the hydroxyapatite substituted with magnesium and a
part of a phosphate group substituted with a carbonate group, and
having a particle size of 5 nm or more and 60 nm or less.
[0013] According to the present invention, hydroxyapatite having a
particle size of 5 nm or more and 60 nm or less and exhibiting
higher bioaffinity, dispersibility, adsorptivity, absorptivity, and
cell activation ability, cosmetic and food containing the same, and
a method for producing the same, can be provided.
[0014] Additional objects and advantages of the invention will be
set forth in the description which follows, and in part will be
obvious from the description, or may be learned by practice of the
invention. The objects and advantages of the invention may be
realized and obtained by means of the instrumentalities and
combinations particularly pointed out hereinafter.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING
[0015] The accompanying drawings, which are incorporated in and
constitute a part of the specification, illustrate embodiments of
the invention, and together with the general description given
above and the detailed description of the embodiments given below,
serve to explain the principles of the invention.
[0016] FIG. 1 is a flowchart illustrating a method for producing
carbonate- and magnesium-substituted hydroxyapatite by
neutralization reaction.
[0017] FIG. 2 is a flowchart illustrating a method for producing
carbonate- and magnesium-substituted hydroxyapatite by a reaction
between two salts.
[0018] FIG. 3 is a flowchart illustrating a method for producing
cosmetics containing carbonate- and magnesium-substituted
hydroxyapatite.
[0019] FIG. 4 is a flowchart illustrating a method for producing
foods containing carbonate- and magnesium-substituted
hydroxyapatite.
DETAILED DESCRIPTION OF THE INVENTION
[0020] Embodiments will be described hereinafter with reference to
the accompanying drawings.
[0021] 1. Carbonate- and Magnesium-Substituted Hydroxyapatite
[0022] In the embodiments, carbonate- and magnesium-substituted
hydroxyapatite is provided.
[0023] Carbonate- and magnesium-substituted hydroxyapatite is a
compound in which a part of calcium of hydroxyapatite having the
chemical formula Ca.sub.10(PO.sub.4).sub.6(OH).sub.2 is substituted
with magnesium and a part of phosphate group is substituted with a
carbonate group. The substitution rate of calcium with magnesium
and the substitution rate of phosphate groups with carbonate groups
is selected such that the particle size of carbonate- and
magnesium-substituted hydroxyapatite is 5 nm or more and 60 nm or
less (more preferably, the particle size is 10 nm or more and 50 nm
or less). The particle size is an average value of the lengths of
the short axis and the long axis direction of primary particles of
carbonate- and magnesium-substituted hydroxyapatite. The primary
particle refers to a particle generated by the growth of a single
crystal nucleus.
[0024] For example, carbonate- and magnesium-substituted
hydroxyapatite may be a compound represented by the chemical
formula ((Ca, Mg).sub.10(PO.sub.4, CO.sub.3).sub.6(OH).sub.2) or
Ca.sub.10-xMg.sub.x(PO.sub.4).sub.6-2/3y(CO.sub.3).sub.y(OH).sub.2.
It is desirable that x is any value from 0.005 to 0.5, and y is any
value from 0.01 to 3.0. A more desirable x value is any value from
0.01 to 0.3, and a more desirable y value is any value from 0.02 to
1.0. In addition, examples of desirable carbonate- and
magnesium-substituted hydroxyapatite are Ca.sub.9.99Mg.sub.0.01
(PO.sub.4).sub.5.98(CO.sub.3).sub.0.02(OH).sub.2,
C.sub.9.7Mg.sub.0.3(PO.sub.4).sub.5.33(CO.sub.3).sub.1(OH).sub.2 or
a mixture of any of these.
[0025] Alternatively, carbonate- and magnesium-substituted
hydroxyapatite is hydroxyapatite, in which calcium of
hydroxyapatite having chemical formula
Ca.sub.10(PO.sub.4).sub.6(OH).sub.2 is substituted with 0.03 wt %
or more and 5 wt % or less of magnesium with respect to calcium,
and a part of the phosphate groups is substituted with 0.2 wt % or
more and 10 wt % or less of the carbonate group with respect to the
phosphate group.
[0026] The carbonate- and magnesium-substituted hydroxyapatite of
the embodiments may be present in the liquid. The formation and/or
growth of secondary particles caused by drying is suppressed due to
the presence in the liquid. The secondary particles are particles
generated by coalescence growth, aggregation, consolidation, etc.,
of the primary particles. As a result, carbonate- and
magnesium-substituted hydroxyapatite can be present in a smaller
particle size. Examples of the liquid include water, an aqueous
solution, emulsion, oil, cream, gel and the like.
[0027] The carbonate- and magnesium-substituted hydroxyapatite of
the embodiments described above can easily be absorbed by the
living body and have higher bioaffinity. In addition, it has a high
effect of adsorbing lipids, proteins, dirt, bacteria, and
odor-causing substances. Their effects are considered to result
from the facts that carbonate- and magnesium-substituted
hydroxyapatite have a smaller particle size compared to
conventional hydroxyapatite, that it has a large surface area ratio
to weight, that it has properties close to living tissue, and that
its surface potential is more positively inclined. For example, the
surface area of carbonate- and magnesium-substituted hydroxyapatite
is 100 m.sup.2/g or more, which is ten times or more that of
conventional hydroxyapatite.
[0028] Furthermore, carbonate- and magnesium-substituted
hydroxyapatite of the embodiments has a high effect of activating
cells. In general, it has been found that hydroxyapatite is
effective in activation of cells such as promotion of collagen
production in fibroblasts or promotion of metabolism in cells
caused by attracting capillaries. Since the carbonate- and
magnesium-substituted hydroxyapatite of the embodiments have a
small particle size and are excellent in absorptivity and
bioaffinity, they exhibit a more excellent cell activation
effect.
[0029] In addition, the carbonate- and magnesium-substituted
hydroxyapatite is uniformly dispersed when mixed with liquids,
emulsions, oils, creams, gels and the like.
[0030] Therefore, the carbonate- and magnesium-substituted
hydroxyapatite of the embodiments is excellent in bioaffinity,
dispersibility, adsorptivity, absorptivity, and cell activation
ability.
[0031] Such carbonate- and magnesium-substituted hydroxyapatite can
be used by addition to, for example, cosmetics or foods described
later, or pharmaceuticals, dental chemicals, kitchen detergents,
laundry detergents, cleaning detergents, disinfectants,
disinfectants, deodorants, fertilizers, agricultural chemicals, a
liquid to be dispersed with a humidifier, or the like.
[0032] 2. Method for Producing Carbonate- and Magnesium-Substituted
Hydroxyapatite
[0033] In the embodiments, the method for producing carbonate- and
magnesium-substituted hydroxyapatite mentioned above is
provided.
[0034] An example of the producing method of the embodiments is
shown in FIG. 1. The producing method is a method for producing
hydroxyapatite by neutralization reaction, comprising, for example,
a step (S101) of preparing the mixed suspension containing
magnesium hydroxide and calcium hydroxide, a step (S102) of
preparing phosphoric acid aqueous solution, and a step (S103) of
mixing the mixed suspension and the phosphoric acid aqueous
solution in the presence of carbon dioxide or carbonate to cause
the neutralization reaction.
[0035] In step S101, a mixed suspension containing magnesium
hydroxide and calcium hydroxide is prepared. The mixed suspension
contains an aqueous solution and solids of magnesium hydroxide and
calcium hydroxide. The molar ratio of magnesium hydroxide to
calcium hydroxide in the mixed suspension may be set such that
carbonate- and magnesium-substituted hydroxyapatite having a
desired substitution rate can be obtained. For example, the molar
ratio of magnesium hydroxide to calcium hydroxide in the mixed
suspension is desirably 1:1000 to 1:100, more desirably 1:500 to
1:50. A desirable concentration of magnesium hydroxide is 0.0002 to
0.01 mol/L, and a desirable concentration of calcium hydroxide is
0.05 to 1.0 mol/L. A temperature of the mixed suspension is
desirably 5 to 50.degree. C.
[0036] In step S102, an aqueous phosphoric acid solution is
prepared. The molar ratio of magnesium hydroxide and calcium
hydroxide contained in the mixed suspension to phosphoric acid, and
the concentration of the phosphoric acid aqueous solution may be
set so as to obtain carbonate- and magnesium-substituted
hydroxyapatite having a desired substitution rate. A desirable
concentration of the phosphoric acid aqueous solution is 0.03 to
0.6 mol/L. A temperature of the phosphoric acid aqueous solution is
desirably 5 to 50.degree. C.
[0037] In step S103, the mixed suspension obtained in step S101 and
the phosphoric acid aqueous solution obtained in step S102 are
mixed in the presence of carbon dioxide gas or carbonate to cause a
neutralization reaction. For example, step S103 is performed by
mixing the mixed suspension and the phosphoric acid aqueous
solution in a carbon dioxide gas atmosphere. Alternatively, a
carbonate may be added in advance to the mixed suspension or the
phosphoric acid aqueous solution, and both may be mixed.
Alternatively, carbonate may be added to the mixture obtained by
mixing the mixed suspension and the phosphoric acid aqueous
solution.
[0038] The carbon dioxide gas may be a gas containing carbon
dioxide, and pure carbon dioxide gas or air may be used as the
carbon dioxide gas. As the carbonate, for example, ammonium
carbonate, sodium bicarbonate, sodium carbonate, potassium
carbonate, or potassium bicarbonate can be used. The concentrations
of carbon dioxide and carbonate are, for example, 0.03 to 0.1 mol/L
and 0.01 to 1.0 mol/L, respectively.
[0039] Mixing may be performed by, for example, stirring. Stirring
may be performed by, for example, a stirring device known to a
person skilled in the art, such as a stirrer, but is desirably
performed using an ultrasonic vibration device. When an ultrasonic
vibration device is used, the output of the device varies depending
on the scale of mass production, but stirring can be performed at
an intensity in the range of 100 W to 2 kW and 10 to 50 kHz.
Aggregation of hydroxyapatite crystals caused by the neutralization
reaction can be thereby prevented. As a result, carbonate- and
magnesium-substituted hydroxyapatite having a smaller particle size
can be obtained. In addition, when the carbon dioxide gas is used,
the phosphoric acid group can be more efficiently replaced with the
carbonate group, by stirring with the strength within the above
range.
[0040] By the neutralization reaction, a suspension containing
carbonate- and magnesium-substituted hydroxyapatite can be
obtained. After the neutralization reaction, the suspension may be
concentrated. Alternatively, a part of the suspension precipitate
may be removed.
[0041] By performing steps S101 to S103 described above, carbonate-
and magnesium-substituted hydroxyapatite having a particle size of
5 nm or more and 60 nm or less can be obtained.
[0042] An example of a producing method in a further embodiment is
shown in FIG. 2. This producing method is a method for producing
hydroxyapatite by reaction between two salts, comprising a step
(S201) of preparing a first solution containing a magnesium salt
and a calcium salt, a step (S202) of preparing a second solution
containing a phosphate, and a step (S203) of mixing the first
solution and the second solution in the presence of carbon dioxide
gas or carbonate to cause the reaction.
[0043] In step S201, the first solution containing a magnesium salt
and a calcium salt is prepared. As the magnesium salt, for example,
magnesium chloride, magnesium nitrate, magnesium sulfate, or
magnesium acetate can be used, but using magnesium chloride is
desirable since it is inexpensive. As the calcium salt, calcium
nitrate, calcium chloride, calcium lactate, or the like can be
used, but using calcium chloride is desirable since it is
inexpensive.
[0044] A molar ratio of calcium salt to calcium salt in the first
solution may be set so as to obtain carbonate- and
magnesium-substituted hydroxyapatite having a desired substitution
rate. For example, the molar ratio of magnesium salt to calcium
salt in the first solution is desirably 1:1000 to 1:100, more
desirably 1:500 to 1:50. A desirable magnesium salt concentration
is 0.0002 to 0.01 mol/L, and a desirable calcium salt concentration
is 0.05 to 1.0 mol/L. A temperature of the first solution is
desirably 5 to 50.degree. C.
[0045] In step S202, a second solution containing phosphate is
prepared. As the phosphate, ammonium phosphate, disodium hydrogen
phosphate, dipotassium hydrogen phosphate, or the like can be used,
but using ammonium phosphate is desirable since ammonia is
volatilized and does not remain.
[0046] The molar ratio of magnesium salt and calcium salt to
phosphate contained in the first solution, and the concentration of
phosphate may be set so as to obtain carbonate- and
magnesium-substituted hydroxyapatite having a desired substitution
rate. A desirable phosphate concentration is 0.03 to 0.6 mol/L. A
temperature of the phosphoric acid aqueous solution is desirably 5
to 50.degree. C.
[0047] In step S203, the first solution obtained in step S201 and
the second solution obtained in step S202 are mixed in the presence
of carbon dioxide or carbonate to cause a salt-salt reaction. For
example, step S203 is performed by mixing the first solution and
the second solution in a carbon dioxide gas atmosphere.
Alternatively, carbonate may be added in advance to the first
solution or the second solution, and both may be mixed.
Alternatively, carbonate may be added to the mixture of the first
solution and the second solution.
[0048] As the carbon dioxide gas and carbonate, for example, the
same carbon dioxide gas and carbonate as described above can be
used. Mixing may be performed by the method described above.
[0049] By the salt-salt reaction, a suspension containing
carbonate- and magnesium-substituted hydroxyapatite is obtained.
After the reaction, the suspension may be concentrated.
Alternatively, a part of the suspension precipitate may be
removed.
[0050] By performing steps S201 to S203 described above, carbonate-
and magnesium-substituted hydroxyapatite having a particle size of
5 nm or more and 60 nm or less can be obtained.
[0051] Carbonate- and magnesium-substituted hydroxyapatite having a
particle size of 5 nm or more and 60 nm or less can be obtained by
the method of the embodiment described above, for the following
reasons. For example, since magnesium atoms are smaller than
calcium atoms, the size of the molecule itself can be made smaller
by replacing calcium with magnesium. In addition, substituted
carbonate group suppresses crystal growth. Furthermore, formation
of large secondary particles can be prevented by not drying the
suspension after the neutralization reaction in step S103 or the
salt-salt reaction in step S203.
[0052] Therefore, according to the present invention,
hydroxyapatite excellent in bioaffinity, dispersibility,
adsorptivity, absorptivity, and cell activation ability, can be
produced.
[0053] Moreover, according to the producing method of the
embodiment, since hydroxyapatite does not need to be synthesized
under alkaline conditions as in the prior art, excess alkali is not
contained in the obtained crystal. For this reason, the carbonate-
and magnesium-substituted hydroxyapatite produced by the producing
method does not cause irritation or damage when brought into
contact with a living body. For example, cosmetics containing
carbonate- and magnesium-substituted hydroxyapatite described later
do not cause irritation or damage to the skin tissue by alkali.
[0054] 3. Cosmetic
[0055] According to a further embodiment, a cosmetic comprising
carbonate- and magnesium-substituted hydroxyapatite having a
particle size of 5 nm or more and 60 nm or less is provided.
[0056] The carbonate- and magnesium-substituted hydroxyapatite
contained in the cosmetic is carbonate- and magnesium-substituted
hydroxyapatite having any one of the above-mentioned particle sizes
of 5 nm or more and 60 nm or less. For example, such hydroxyapatite
may be produced by the above producing method.
[0057] The cosmetic may be any known cosmetic, for example, a
mixture of materials selected from purified water, other liquids,
oil, soap base, alcohol such as ethanol or glycerin, fragrance,
stearic acid, squalene, propylene glycol, petrolatum, surfactant,
paraffin, various vitamins, collagen and the like. Such a cosmetic
includes, for example, hair shampoo, rinse, conditioner, treatment,
rinse-in shampoo, body shampoo, hand shampoo, facial cleansing
foam, cleansing emulsion, cleansing cream, cleansing oil, soap,
liquid soap, liquid bath agent, lotion, cosmetic liquid, cosmetic
oil, emulsion, cream, gel, toothpaste powder, toothpastes,
mouthwash, whitening liquid deodorant, or the like, but is not
limited to these. In particular, since carbonate- and
magnesium-substituted hydroxyapatite is better adsorbed with lipids
and oils such as oleic acid, oleyl oleate, and olive oil, the
cosmetic desirably contains them. In addition, when containing
vitamin C, hydroxyapatite amplifies the antioxidant power of
vitamin C, and thus can provide a cosmetic with a higher skin
quality improving effect.
[0058] A concentration of carbonate- and magnesium-substituted
hydroxyapatite in the cosmetic is desirably, for example, 0.001 wt
% or more and 15 wt % or less.
[0059] Since carbonate- and magnesium-substituted hydroxyapatite
has a small particle size as described above, it easily enters
pores and epidermis, and has a high effect of adsorbing proteins,
lipids, dirt, bacteria, or substances that cause odor. For this
reason, by using the cosmetic, sebum, keratin plugs, darkening,
keratin and the like of skin can be efficiently removed, and acne,
athlete's foot, worm odor, aging odor and the like can be prevented
and improved. In addition, as described above, carbonate- and
magnesium-substituted hydroxyapatite promotes collagen production
in fibroblasts, and promotes cell metabolism by attracting
capillaries. Based on these matters, skin quality and hair quality
can be further improved by using the cosmetics. In addition, since
the hydroxyapatite mentioned here has a small particle size and
hardly gives physical irritation to the skin, the cosmetic feeling
is smoother. Furthermore, if the hydroxyapatite contained in the
cosmetic is produced by the above producing method, it does not
cause irritation and damage to the skin due to alkali.
[0060] When the cosmetic is toothpaste, toothpaste, mouthwash,
whitening solution, or the like, the cosmetic has a high effect of
adsorbing and removing tooth dirt, mutans bacteria, plaque and the
like. In addition, carbonate- and magnesium-substituted
hydroxyapatite has a high effect of supplementing minerals in the
decalcified subsurface portion of the tooth enamel that is
dissolved by the acid generated by bacteria in the plaque or the
acid of food and drink. This is considered to result from the fact
that the size, composition and structure of the carbonate- and
magnesium-substituted hydroxyapatite are similar to those of the
hydroxyapatite contained in the teeth. Therefore, by using the
cosmetic, it is possible to fill and repair the damages on the
tooth surface, remineralize the initial caries, and smooth the
surface to prevent adhesion of plaque, dirt and the like.
[0061] Moreover, since the carbonate- and magnesium-substituted
hydroxyapatite is uniformly dispersed to the material, the cosmetic
uniformly containing the ingredients is provided.
[0062] 4. Method for Producing Cosmetic
[0063] According to the embodiment, a method for manufacturing the
cosmetic is provided.
[0064] Part (a) and (b) of FIG. 3 show an example of a method for
producing the cosmetic. The method for producing the cosmetic
includes a step (S301) of obtaining a carbonate- and
magnesium-substituted hydroxyapatite-containing suspension by
executing S101 to S103 of the above method for producing the
carbonate- and magnesium-substituted hydroxyapatite, and a step
(S302) of containing the carbonate- and magnesium-substituted
hydroxyapatite-containing suspension in the cosmetic ((a) of FIG.
3). Alternatively, the method of manufacturing the cosmetic
includes a step (S303) of obtaining carbonate- and
magnesium-substituted hydroxyapatite-containing suspension by
performing S201 to S203 of the above method for producing the
carbonate- and magnesium-substituted hydroxyapatite, and a step
(S304) of containing the carbonate- and magnesium-substituted
hydroxyapatite-containing suspension in the cosmetic ((b) of FIG.
3).
[0065] Step S301 and step S303 are the same as those of the
above-described "2. Method for Producing Carbonate- and
Magnesium-Substituted Hydroxyapatite". In step S302 and step S304,
the carbonate- and magnesium-substituted hydroxyapatite-containing
suspension is made to be contained in the cosmetic. Step S302 and
step S304 may be performed, for example, by adding the suspension
to any one of the above-described cosmetics produced in advance and
mixing, or by producing cosmetic from raw materials of any
cosmetics to which the suspension is added. Method for mixing may
be selected depending on the type of cosmetic, and mixing can be
performed by, for example, a mixer, a kneader, a stirrer, a
disperser, a mixing device or the like.
[0066] According to the cosmetic producing method of the
embodiment, carbonate- and magnesium-substituted hydroxyapatite can
be contained in the cosmetic without drying. Cosmetics containing
carbonate- and magnesium-substituted hydroxyapatite having a small
particle size which are not aggregated and/or solidified can be
thereby provided.
[0067] 5. Food
[0068] According to a further embodiment, food containing
carbonate- and magnesium-substituted hydroxyapatite is
provided.
[0069] The carbonate- and magnesium-substituted hydroxyapatite
contained in the foods is any of the above-described carbonate- and
magnesium-substituted hydroxyapatite. For example, such
hydroxyapatite may be produced by the above producing method.
[0070] The foods are, for example, beverages such as water, coffee,
tea, fruit juice, and soft drinks, dairy products such as milk,
yogurt and cheese, cooking oils such as salad oil and olive oil,
seasonings, ice creams, soups, and cooked foods (retort foods), pet
foods or supplements, but are not limited thereto. Furthermore, the
foods may contain additives such as vitamins, and particularly
desirably contain vitamin D and vitamin C. When containing vitamin
D, the absorption efficiency of calcium is promoted. Therefore,
such foods are particularly suitable for sports drinks, and are
highly effective in preventing and improving osteoporosis and the
like. In addition, since vitamin D is activated by hydroxyapatite,
foods having a high absorption efficiency of vitamin D can be
provided. In the case of containing vitamin C, hydroxyapatite
amplifies the antioxidant power of vitamin C, and therefore can
provide foods having a higher antioxidant power.
[0071] The concentration of carbonate- and magnesium-substituted
hydroxyapatite in the food is, for example, 0.001 wt % or more and
10 wt % or less.
[0072] Since the carbonate- and magnesium-substituted
hydroxyapatite of the embodiment has a small particle size and high
absorptivity, it is efficiently absorbed from the stomach and
intestine. For this reason, magnesium, calcium, and phosphoric acid
can be ingested more efficiently by ingesting the foods.
Furthermore, since the carbonate and magnesium-substituted
hydroxyapatite is similar in composition to the inorganic
components contained in bones and teeth, the foods are more
effective in strengthening bone quality. In addition, since the
carbonate- and magnesium-substituted hydroxyapatite of the
embodiment can be uniformly dispersed in the foods, the foods that
uniformly contain ingredients are provided.
[0073] 6. Method for Producing Food
[0074] According to the embodiment, a method for producing the
above foods is provided.
[0075] The examples of the method for producing the foods are shown
in (a) and (b) of FIG. 4. The method for producing the foods
includes a step (S401) of obtaining carbonate- and
magnesium-substituted hydroxyapatite-containing suspension by
executing S101 to S103 of the above method for producing the
carbonate- and magnesium-substituted hydroxyapatite, and a step
(S402) of containing the carbonate- and magnesium-substituted
hydroxyapatite-containing suspension in the foods ((a) of FIG. 4).
Alternatively, the method for producing the foods includes a step
(S403) of obtaining carbonate- and magnesium-substituted
hydroxyapatite-containing suspension by executing S201 to S203 of
the above method for producing the carbonate- and
magnesium-substituted hydroxyapatite, and a step (S404) of
containing the carbonate- and magnesium-substituted
hydroxyapatite-containing suspension in the foods ((b) of FIG.
4).
[0076] Step S401 or step S402 is the same as that of the
above-described "2. Method for Producing Carbonate- and
Magnesium-Substituted Hydroxyapatite". In step S402 or step S404,
the carbonate- and magnesium-substituted hydroxyapatite-containing
suspension is made to be contained in the foods. Step S402 or S404
may be performed, for example, by adding the suspension to any one
of the above-described foods produced in advance and mixing, or by
producing foods from raw materials of any foods to which the
suspension is added. Mixing may be selected depending on the type
of foods, and can be performed by, for example, a mixer, a kneader,
a stirrer, a disperser, a mixing device or the like.
[0077] According to the food producing method of the embodiment,
carbonate- and magnesium-substituted hydroxyapatite can be
contained in the foods without drying. Foods containing carbonate-
and magnesium-substituted hydroxyapatite with a small particle size
which are not aggregated and/or solidified can be thereby
provided.
[0078] Examples of the present invention will be described
hereinafter in detail.
Example 1
[0079] A 1 L suspension containing 0.001 mol and 0.01 mol magnesium
hydroxide and 0.1 mol and 1 mol calcium hydroxide in water at
22.degree. C. and 37.degree. C. was prepared. Next, a 1 L aqueous
solution containing 0.06 mol to 0.6 mol of phosphoric acid at
22.degree. C. and 37.degree. C. was prepared. The suspension and
aqueous solution at 22.degree. C. and the suspension and aqueous
solution at 37.degree. C. were stirred and suspended in an
atmosphere of carbon dioxide (air) using an ultrasonic agitator set
at intensity of 600 W and 20 kHz, respectively, to obtain
suspensions.
[0080] When the obtained suspensions were analyzed by X-ray
diffraction (XRD), a typical hydroxyapatite crystal pattern was
observed in each of the suspensions. That is, it was confirmed that
the basic structure of the particles contained in the obtained
suspensions is the same as that of hydroxyapatite.
[0081] Furthermore, when the obtained suspensions were analyzed by
Fourier Transform Infrared Spectroscopy (FTIR), absorption peaks
appeared in hydroxyl groups and carbonate groups. That is, it was
confirmed that hydroxyapatite containing carbonic acid was
synthesized.
[0082] In addition, as a result of analyzing the obtained
suspensions by Inductively Coupled Plasma (ICP), it was confirmed
that the particles contained in the obtained suspensions contained
approximately 0.03 to 0.9 wt % of magnesium and approximately 0.5
to 5 wt % of carbonate ions. The weight percent of the substituted
magnesium and carbonate ions was calculated by converting the
molecular weight of hydroxyapatite to 1 kg.
[0083] It was confirmed from the analysis results of XRD, FTIR, and
ICP described above that the obtained suspensions contained
carbonate- and magnesium-substituted hydroxyapatite.
[0084] As a result of calculating the crystallite size of the
microcrystal obtained by synthesis from the half-value width of the
X-ray diffraction method, the size of the C axis (long axis
direction) and A axis (short axis direction) of crystallite, i.e.,
the average primary particle size was widely distributed at 10 m or
more and 60 nm or less. As the amount of magnesium and carbonate
ion substitution was greater, the primary particle size was smaller
and close to the minimum value of 10 nm.
[0085] The sedimentation of the suspensions obtained by the
synthesis was slower as the size of the primary particles and the
size of the secondary particles were smaller. In addition, no
precipitation of crystals was observed from the supernatant fluid
of the suspensions. That is, it was confirmed that the carbonate-
and magnesium-substituted hydroxyapatite contained in the
supernatant fluid contained floating microcrystals.
[0086] When the surface area of the obtained particles was measured
by a gas adsorption method (BET method), the surface area was in
the range of 50 m.sup.2/g to 120 m.sup.2/g. The surface area was
inversely proportional to the size of the primary particles. In
contrast, the surface area of commercially available hydroxyapatite
powder is 10 m.sup.2/g or less.
[0087] <Evaluation of Adsorptivity of Lipid (1)>
[0088] A first column filled with the powder of particles of
Example 1 obtained by synthesis at room temperature of 22.degree.
C. and a second column filled with commercially available
hydroxyapatite powder were prepared, and olive oil diluted with
normal hexane was passed through each of the first column and the
second column. After that, the first column and the second column
were washed with normal hexane, and the amount of lipid peroxide
contained in each the washing solutions was measured. This
experiment was performed five times, and the average value of the
amount of lipid peroxide adsorbed was calculated by the iodine
titration method. As a result, assuming that the adsorption amount
of lipid peroxide contained in the washing solution of the first
column was 100, the adsorption amount of lipid peroxide contained
in the second column was in the range of 60 to 70. That is, it was
confirmed that carbonate- and magnesium-substituted hydroxyapatite
adsorbs more lipids than normal hydroxyapatite.
[0089] <Evaluation of Adsorptivity of Lipid (2)>
[0090] Suspension containing 1 wt % of commercially available
hydroxyapatite crystals, 1 wt % of carbonate- and
magnesium-substituted hydroxyapatite suspension obtained in Example
1, 1 wt % of .alpha.-alumina-containing purified water suspension,
and 1 wt % of sericite-containing purified water suspension were
prepared at 100 mL each. 5 g of oleic acid, oleyl oleate, and olive
oil were added to each of the suspensions and immersed for 24
hours. After that, each suspension was washed with diethyl ether,
and the amounts of adsorbed oleic acid, oleyl oleate and olive oil
were analyzed by gravimetric analysis. As a result, assuming that
the lipid adsorption amount of the suspension containing carbonate-
and magnesium-substituted hydroxyapatite obtained in Example 1 is
1, the lipid adsorption amount of the suspension containing
commercially available hydroxyapatite was approximately 0.8. In
addition, the result that an .alpha.-alumina containing purified
water suspension and a sericite containing purified water
suspension hardly adsorb a lipid was obtained.
[0091] <Evaluation of Dispersibility>
[0092] The carbonate- and magnesium-substituted hydroxyapatite
suspension of Example 1 and commercially available hydroxyapatite
powder were added to 100 g of commercially available cosmetics such
as emulsions, cleansing creams, creams, and soaps, or commercially
available foods such as drinking water, yogurt and juice so as to
be 0.1 to 10 wt %.
[0093] As a result of observing the obtained cosmetics and foods,
the carbonate- and magnesium-substituted hydroxyapatite contained
in these cosmetics and foods and obtained in Example 1 had less
precipitates and were well dispersed as compared with commercially
available hydroxyapatite.
Example 2: Production and Evaluation of Lotion
[0094] An alkaline lotion (1000 mL in total) containing 3 g of
potassium hydroxide, 1 g of carbonate and magnesium-substituted
hydroxyapatite of Example 1, 200 mL of glycerin, 250 mL of ethanol,
and 550 mL of purified water was prepared.
[0095] Ten adult male and female subjects used the lotion and
lotion produced by replacing carbonate- and magnesium-substituted
hydroxyapatite with 1 g of commercially available hydroxyapatite
(.alpha.-alumina or sericite) in the above composition, and
compared the effect of removing dirt and the feeling of use. As a
result, eight of ten subjects had an impression that the skin
lotion containing the carbonate- and magnesium-substituted
hydroxyapatite had the lowest lipid and had a refreshing
feeling.
Example 3: Production and Evaluation of Cream
[0096] Cream (100 g) containing 10 to 20 wt % of stearic acid, 0.5
to 1.0 wt % of potassium hydroxide, 10 to 20 wt % of glycerin, 0.5
to 1.0 wt % of perfume, 5 to 10 wt % of carbonate- and
magnesium-substituted hydroxyapatite of Example 1, an appropriate
amount of an antioxidant, a bactericidal antibacterial agent and
purified water was produced. As a result of visual observation of
the hydroxyapatite dispersed in the cream, hydroxyapatite was well
dispersed.
[0097] The cream and a cream produced by replacing carbonate- and
magnesium-substituted hydroxyapatite of the above composition with
commercially available hydroxyapatite were applied to faces of ten
subjects including five males and five females and then washed. As
a result, all the subjects had an impression that the cream
containing the carbonate- and magnesium-substituted hydroxyapatite
was smoother and had a refreshing feeling after washing.
Example 4: Production and Evaluation of Water Soap
[0098] 1 to 5% of carbonate- and magnesium-substituted
hydroxyapatite suspension of Example 1 was added to 30% aqueous
solution of temporary soap obtained by saponifying fats and oils
such as vegetable oil with potassium hydroxide, and a thickening
binder and a moisturizing component were blended to obtain an
appropriate viscosity, and liquid soap was thereby produced.
[0099] Ten adult male and female subjects used the liquid soap and
the liquid soap produced by replacing the carbonate- and
magnesium-substituted hydroxyapatite of the above composition with
commercially available hydroxyapatite, and compared the effect of
removing dirt and feeling of use. As a result, seven persons had an
impression that the liquid soap with the addition of carbonate- and
magnesium-substituted hydroxyapatite removed dirt better and had a
refreshing feeling of use after use.
Example 5: Method for Producing Bath Agent
[0100] A bath agent containing 10 g of 1 wt % carbonate- and
magnesium-substituted hydroxyapatite suspension of Example 1,
purified water 90 g, sake 10 g, natural salt 1 g, citric acid 50 g,
potato starch 50 g, jojoba oil 2 g, and 1 g of cypress essential
oil was produced.
[0101] Ten adult male and female subjects put 20 g of the above
bath agent into a 200 L bathtub and bathed. When the bath agent was
compared with a bath agent produced by replacing the carbonate- and
magnesium-substituted hydroxyapatite of the above composition with
commercially available hydroxyapatite, eight of ten subjects had an
impression that the bath agent to which the carbonate- and
magnesium-substituted hydroxyapatite were added had less sediment
and was excellent in fluidity. In addition, there was also an
impression that the skin surface was smoothed by removing dirt and
keratin from the skin surface.
Example 6: Production and Evaluation of Yogurt
[0102] Yogurt was produced by adding 10 mL of 0.1 wt % carbonate-
and magnesium-substituted hydroxyapatite suspension of Example 1 to
100 g of commercially available yogurt.
[0103] As a result of visual observation of the carbonate- and
magnesium-substituted hydroxyapatite contained in the yogurt,
neither aggregation nor precipitation occurred, and hydroxyapatite
was well dispersed.
Example 7: Production and Evaluation of Orange Juice
[0104] An orange juice was produced by adding 10 mL of 0.1 wt %
carbonate- and magnesium-substituted hydroxyapatite suspension of
Example 1 to 90 g of commercially available 100% orange juice. The
taste of the orange juice produced was equivalent to the taste of
commercial orange juice before adding the carbonate- and
magnesium-substituted hydroxyapatite suspension.
Example 8: Production and Evaluation of Calcium Supplementing
Drinking Water
[0105] Calcium supplemented drinking water was produced by adding 1
mL of a 1%-suspended carbonate- and magnesium-substituted
hydroxyapatite suspension of Example 1 to 100 g of 0.1% saline
solution. When the calcium supplemented drinking water and calcium
supplemented drinking water produced by replacing carbonate- and
magnesium-substituted hydroxyapatite of the above composition with
commercially available hydroxyapatite were visually observed and
compared, the commercially available hydroxyapatite powder was
precipitated and aggregated, but the carbonate- and
magnesium-substituted hydroxyapatite were well dispersed without
precipitation or aggregation.
[0106] In addition, the bending strength of a femur of a mouse that
have been given this calcium-supplemented drinking water every day
for 3 months was greater by approximately 20% than the bending
strength of a mouse that have been supplied with additive-free
drinking water every day for 3 months.
Example 9
[0107] A 1 L aqueous solution containing 0.1 mol magnesium chloride
and 0.1 mol calcium nitrate was prepared. A 1 L aqueous solution
containing 0.06 mol of ammonium phosphate was prepared. Both of the
aqueous solutions were stirred with an ultrasonic stirring device
adjusted at 37.degree. C. and set at 600 W and 20 kHz strength in a
carbon dioxide (air) atmosphere to obtain a suspension.
[0108] As a result of analyzing the obtained suspension by XRD,
FTIR, and ICP in the same manner as in Example 1, it was confirmed
that approximately 0.5 wt % magnesium and approximately 2 wt %
carbonate ions were contained in the suspension. In addition, it
was confirmed that the suspension was a suspension of approximately
0.5 wt % of carbonate- and magnesium-substituted hydroxyapatite
crystals.
Example 10
[0109] A 1 L aqueous solution containing 0.025 mol sodium
bicarbonate and 0.25 mol calcium salt was prepared. 15 g of 85%
aqueous phosphoric acid solution was prepared. A calcium hydroxide
aqueous solution and phosphoric acid were stirred using an
ultrasonic stirring device set to a strength of 37.degree. C., 600
W, and 20 kHz to obtain a suspension.
[0110] As a result of analyzing the obtained suspension by XRD,
FTIR, and ICP in the same manner as in Example 1, it was confirmed
that 0.2 wt % magnesium and approximately 5 wt % carbonate ions
were contained in the suspension. In addition, it was confirmed
that the microcrystals were carbonate- and magnesium-substituted
hydroxyapatite crystals. Furthermore, the size of primary particles
of the carbonate- and magnesium-substituted hydroxyapatite
microcrystals obtained was 20 nm or less.
[0111] When the adsorptivity and dispersibility of the carbonate-
and magnesium-substituted hydroxyapatite obtained in Examples 9 and
10 were evaluated by the methods described above, the same results
as those of Example 1 were obtained. In addition, when the
carbonate- and magnesium-substituted hydroxyapatite of Examples 9
and 10 was used to be applied to Examples 2 to 8 instead of the
carbonate- and magnesium-substituted hydroxyapatite of Example 1,
the same results as those of the case using the carbonate- and
magnesium-substituted hydroxyapatite of Example 1 were
obtained.
[0112] Additional advantages and modifications will readily occur
to those skilled in the art. Therefore, the invention in its
broader aspects is not limited to the specific details and
representative embodiments shown and described herein. Accordingly,
various modifications may be made without departing from the spirit
or scope of the general inventive concept as defined by the
appended claims and their equivalents.
* * * * *