U.S. patent application number 15/557682 was filed with the patent office on 2018-02-22 for an ascorbic acid dispersion material, and its manufacturing method.
The applicant listed for this patent is Takanori OTA. Invention is credited to Takanori OTA.
Application Number | 20180049963 15/557682 |
Document ID | / |
Family ID | 54330216 |
Filed Date | 2018-02-22 |
United States Patent
Application |
20180049963 |
Kind Code |
A1 |
OTA; Takanori |
February 22, 2018 |
AN ASCORBIC ACID DISPERSION MATERIAL, AND ITS MANUFACTURING
METHOD
Abstract
To provide an ascorbic acid dispersion material with higher
chemical stability, and with superior usage characteristics, such
as spreadability and smoothness, upon application onto skin. The
ascorbic acid dispersion material is obtained by dispersing
ascorbic acid crystals in a solvent, whereby the ascorbic acid
crystals have a flat plate shape, a thickness of 0.05 to 3 .mu.m,
and an average particle diameter of 50 to 100 .mu.m.
Inventors: |
OTA; Takanori;
(Musashino-shi, Tokyo, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
OTA; Takanori |
Musashino-shi, Tokyo |
|
JP |
|
|
Family ID: |
54330216 |
Appl. No.: |
15/557682 |
Filed: |
March 24, 2016 |
PCT Filed: |
March 24, 2016 |
PCT NO: |
PCT/JP2016/059343 |
371 Date: |
September 12, 2017 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61Q 19/00 20130101;
A61K 2800/412 20130101; A61K 8/04 20130101; A61Q 19/08 20130101;
A61K 47/10 20130101; A61P 3/02 20180101; A61K 31/375 20130101; A61K
8/676 20130101; A61K 8/345 20130101; A61P 17/18 20180101 |
International
Class: |
A61K 8/67 20060101
A61K008/67; A61K 8/04 20060101 A61K008/04; A61K 8/34 20060101
A61K008/34; A61Q 19/08 20060101 A61Q019/08; A61K 31/375 20060101
A61K031/375; A61K 47/10 20060101 A61K047/10 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 31, 2015 |
JP |
2015-074620 |
Claims
1. An ascorbic acid dispersion material, which is obtained by
dispersing an ascorbic acid crystal in a solvent, wherein the
ascorbic acid crystal has a flat plate shape, a thickness of 0.05
to 3 .mu.m, and an average particle diameter of 50 to 100
.mu.m.
2. The ascorbic acid dispersion material according to claim 1,
wherein the particle size distribution of the ascorbic acid crystal
has a distribution such that particles having a particle diameter
of 30 to 120 .mu.m account for 40 to 80% of the overall
particles.
3. The ascorbic acid dispersion material according to claim 1,
wherein the solvent is one or more selected from a group consisting
of glycerin, diglycerin, polyglycerin represented by the following
formula, and propylene glycol. ##STR00002##
4. The ascorbic acid dispersion material according to claim 1,
wherein the ascorbic acid concentration is 20 to 40 wt %.
5. The ascorbic acid dispersion material according to claim 1,
wherein the average density is 1.3 to 1.4 g/cm.sup.3.
6. The ascorbic acid dispersion material according to claim 1,
wherein the viscosity is 5000 to 300,000 mPas.
7. A manufacturing method of the ascorbic acid dispersion material
according to claim 1, comprising: a heating step involving infusing
an ascorbic acid into a solvent comprising one or more selected
from a group consisting of glycerin, diglycerin, polyglycerin
represented by the following formula, and propylene glycol, and
heating the ascorbic acid to a predetermined temperature to
dissolve the ascorbic acid; a cooling step involving cooling the
solution with the ascorbic acid dissolved therein at a cooling rate
of 5 to 20.degree. C./min until the temperature of the solution
reaches 35 to 50.degree. C. to remove heat from the solution; and a
growth step involving storing the solution after completion of the
cooling step at 27 to 38.degree. C. for a predetermined period to
promote crystal growth. ##STR00003##
8. A skin care preparation, which contains an ascorbic acid
dispersion material according to claim 1.
Description
TECHNICAL FIELD
[0001] The present invention relates to an ascorbic acid dispersion
material, as well as its manufacturing method.
BACKGROUND ART
[0002] Because ascorbic acid has an antioxidative action, and is
involved in the generation and maintenance of collagen, thereby
having an anti-aging effect on skin, ascorbic acid is blended into
whitening cosmetics, etc., as a safe whitening material, and also
as a whitening component for preventing spots and freckles,
etc.
[0003] Moreover, ascorbic acid is also used in drugs for the
prevention and treatment of vitamin C deficiency diseases, as well
as for replenishment purposes, etc., and many other pharmacological
effects are known. Examples of these pharmacological effects may
include such effects as: (action on capillary blood vessels)
reinforcement of capillary resistance, amelioration of bleeding
tendencies, or increase in blood clotting; (action on
adrenocortical functions) biosynthesis promotion or catabolism
suppression with respect to steroid hormones, (action on connective
tissues) involvement in the hydroxylation process from proline to
hydroxyproline, and particularly in the case of collagen, in the
formation/maintenance of an intercellular matrix and collagen, and
in increasing collagen through the administration of ascorbic acid,
(action on bone tissue) promoting bone formation, and (action on
the generation of melanin pigment) inhibition of the oxidation
process from dopa to dopaquinone during the process of generating
melanin from tyrosine, and suppression of melanin pigment
generation. As a result, ascorbic acid is also used for: treatment
of capillary bleeding, such as nasal bleeding, gingival bleeding,
and hematuria; dysadrenocorticism; bone matrix formation/bone union
promotion in fractures; suppression of pigment deposition after
chloasma/ephelides/inflammation; and chemical poisoning involving
alcohol, nicotine, etc.
[0004] Further, ascorbic acid is also blended in with cold drinks,
storage foods, confectionery, health foods, etc.
[0005] Unfortunately, when ascorbic acid is dissolved in water, it
becomes very unstable, and easily oxidized as a result of light,
heat, the pH state, metal ions, etc.; even if a highly concentrated
aqueous solution of ascorbic acid is prepared, it is difficult to
store in a stable manner. Moreover, while ascorbic acid is useful
as a percutaneous absorption-type pharmaceutical such as cosmetic
materials, as mentioned above, the high concentration is
problematic in that it enables crystallization, leading to poor
usage characteristics.
[0006] For this reason, various technologies have been proposed
relating to ascorbic acid dispersion liquids, etc., that are able
to stably store ascorbic acid at a high concentration, as well as
various dispersion liquids in which even at high concentrations
usage characteristics do not worsen.
[0007] For example, a percutaneous absorption liquid including an
ascorbic acid suspension liquid containing ascorbic acid particles
of less than 20 .mu.m, etc., is proposed.
[0008] Moreover, the present applicants have so far proposed, in
Patent Documents 1 and 2, for example, a glycerin liquid suspension
of an ascorbic acid that is useful as a cosmetic substrate
containing ascorbic acid having superior usage characteristics
(spreadability and smoothness upon application onto skin), wherein
the content of the ascorbic acid is 13% by mass or more, and part
of the ascorbic acid is dissolved in glycerin or
glycerin-containing diglycerin, at a concentration of 8 to 12% by
mass, while the remaining ascorbic acid is deposited as a fine
crystal having a particle diameter of 25 .mu.m or smaller, and
homogeneously dispersed.
[0009] Moreover, for example, Patent Document 3 proposes, as a
manufacturing method for a homogeneous solution of transparent and
stable glycerin containing a high concentration of ascorbic acid,
as well as a cosmetic material including the glycerin solution, a
manufacturing method for a glycerin solution having an ascorbic
acid concentration of 16 to 45% by mass, wherein an ascorbic acid,
glycerin, and ethyl alcohol are mixed to dissolve the ascorbic
acid, and subsequently the ethyl alcohol is removed, as well as a
cosmetic material including the glycerin solution.
[0010] Moreover, for example, Patent Document 4 proposes, as a
stable storage method providing superior quality in a glycerin
solution containing a high concentration of ascorbic acid, a low
temperature storage method that stores a glycerin solution having
an ascorbic acid concentration of 13% by mass or higher, at
0.degree. C. to -30.degree. C.
PRIOR ART DOCUMENTS
Patent Documents
[0011] Patent Document 1: International Publication WO No.
2008/050676 [0012] Patent Document 2: Japanese Unexamined Patent
Application Publication No. 2013-166778 [0013] Patent Document 3:
Japanese Unexamined Patent Application Publication No. 2007-332094
[0014] Patent Document 4: Japanese Unexamined Patent Application
Publication No. 2008-013493
SUMMARY OF THE INVENTION
Problems to be Solved by the Invention
[0015] Unfortunately, percutaneous absorption liquids, including
the ascorbic acid suspension liquid containing ascorbic acid
particles of less than 20 .mu.m as mentioned above, etc., have
crystal particles that are too small, poor storage stability, and
poor usage characteristics and absorption as a percutaneous
absorption type pharmaceutical.
[0016] Moreover, in the proposals in Patent Documents 1 to 4, while
there is improved chemical stability of ascorbic acid, as well as
spreadability and smoothness upon application onto skin, even more
advanced usage characteristics and storage stability are currently
required.
[0017] For this reason, there is a demand for the development of
ascorbic acid dispersion materials that have higher chemical
stability and superior usage characteristics, such as spreadability
and smoothness upon application onto skin.
[0018] Accordingly, the object of the present invention is to
provide an ascorbic acid dispersion material that has higher
chemical stability, and superior usage characteristics, such as
spreadability and smoothness upon application onto skin.
Means for Solving the Problems
[0019] As a result of extensive research in order to solve the
abovementioned problems, the present inventors found that the
crystalline form of ascorbic acid varies under conditions of
heating, cooling, and crystal growth in the manufacturing method of
an ascorbic acid dispersion material, and it was also found that
there are a suitable particle diameter range and particle shape
that improve usage characteristics according to the particle
diameter of the crystal particles, leading to the completion of the
present invention.
[0020] In other words, the present invention provides each of the
following inventions.
[0021] 1. An ascorbic acid dispersion material, which is obtained
by dispersing an ascorbic acid crystal in a solvent, wherein the
ascorbic acid crystal has a flat plate shape, and an average
particle diameter of 50 to 100 .mu.m.
[0022] 2. The ascorbic acid dispersion material according to 1,
wherein the particle size distribution of the ascorbic acid crystal
has a distribution such that particles having a particle diameter
of 30 to 120 .mu.m account for 40 to 80% of the overall
particles.
[0023] 3. The ascorbic acid dispersion material according to 1,
wherein the solvent contains glycerin.
[0024] 4. The ascorbic acid dispersion material according to 1,
wherein the ascorbic acid concentration is 20 to 40 wt %.
[0025] 5. The ascorbic acid dispersion material described, wherein
the ascorbic acid crystal has a thickness of 0.05 to 3 .mu.m.
[0026] 6. The ascorbic acid dispersion material according to 1,
wherein the average density is 1.3 to 1.4 g/cm.sup.3.
[0027] 7. The ascorbic acid dispersion material according to 1,
wherein the viscosity is 5000 to 300,000 mPas.
[0028] 8. A manufacturing method of an ascorbic acid dispersion
material according to 1, including: a heating step involving
infusing an ascorbic acid into a solvent, and heating the ascorbic
acid to a predetermined temperature to dissolve the ascorbic acid;
a cooling step involving cooling the solution with the ascorbic
acid dissolved therein to remove heat from the solution; and a
growth step involving storing the solution after completion of the
cooling step for a predetermined period to promote crystal
growth.
Effects of the Invention
[0029] The ascorbic acid dispersion material of the present
invention has higher chemical stability, and superior usage
characteristics, such as spreadability and smoothness upon
application onto skin.
[0030] Moreover, the manufacturing method of the present invention
enables the ascorbic acid dispersion material of the present
invention to be more efficiently manufactured.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] FIG. 1 is a scanning electron micrograph image (drawing
substitute photograph) of an ascorbic acid crystal in Example
1.
[0032] FIG. 2 is a scanning electron micrograph image (drawing
substitute photograph) of an ascorbic acid crystal in Example
2.
[0033] FIG. 3 is a scanning electron micrograph image (drawing
substitute photograph) of an ascorbic acid crystal in Example
3.
[0034] FIG. 4 is a scanning electron micrograph image (drawing
substitute photograph) of a commercially available ascorbic acid
crystal powder.
[0035] FIG. 5 is a chart illustrating the results of the particle
size distribution analysis of an ascorbic acid dispersion material
in Example 1.
[0036] FIG. 6 is a chart illustrating the results of the particle
size distribution analysis of an ascorbic acid dispersion material
in Example 2.
[0037] FIG. 7 is a chart illustrating the results of the particle
size distribution analysis of an ascorbic acid dispersion material
in Example 3.
[0038] FIG. 8 is a chart illustrating the results of the X-ray
diffraction analysis of the ascorbic acid crystal in Example 1.
[0039] FIG. 9 is a chart illustrating the results of the X-ray
diffraction analysis of the ascorbic acid crystal in Example 2.
[0040] FIG. 10 is a chart illustrating the results of the X-ray
diffraction analysis of the ascorbic acid crystal in Example 3.
MODE FOR CARRYING OUT THE INVENTION
[0041] While not limited to the following, the ascorbic acid
dispersion material of the present invention will now be
described.
[0042] (Overall Configuration of the Ascorbic Acid Dispersion
Material)
[0043] The ascorbic acid dispersion material of the present
invention is obtained by dispersing an ascorbic acid crystal in a
solvent, wherein the abovementioned ascorbic acid crystal has a
specific shape and particle diameter.
[0044] The shape and particle diameter of the abovementioned
ascorbic acid crystal will be described in detail later.
[0045] (Solvent)
[0046] While the abovementioned solvent used in the present
invention is not particularly limited, for example, glycerin,
diglycerin, polyglycerin represented by the following formula,
propylene glycol, etc., can be used, and any one of these may be
used, or two or more of these may be mixed and used.
##STR00001##
[0047] In the formula, n is an integer from 3 to 10.
[0048] Among other possibilities, the solvent is preferably
glycerin and diglycerin, from the perspective that ascorbic acid
tends to have the crystal shape described below, and from the
perspectives of safety to the human body including skin, and usage
characteristics upon application onto skin. Moreover, in obtaining
a mixed solvent of glycerin and diglycerin, the blending ratio of
diglycerin is preferably 0.1 to 5 wt % in the solvent.
[0049] (Ascorbic Acid Crystal)
[0050] The abovementioned ascorbic acid crystal in the ascorbic
acid dispersion material of the present invention has a flat plate
shape. Moreover, the abovementioned ascorbic acid crystal has
gentle angles in the corners, with few sharp angles (see FIGS. 1 to
3)
[0051] As a result, the ascorbic acid dispersion material of the
present invention has a smoothness upon application onto skin, with
superior usage characteristics. Moreover, it is not known why the
crystals tend to not be aggregated, as a result of which the
chemical stability of the ascorbic acid is increased.
[0052] Note that while crystals having shapes other than a flat
plate shape, such as a sphere, may be present among the ascorbic
acid crystals, the ratio of such crystals is generally 10 wt % or
lower.
[0053] While the thickness of the abovementioned ascorbic acid
crystal is not particularly limited, it is preferably 0.05 to 3
.mu.m. Within this range, the abovementioned usage characteristics
are superior.
[0054] Note that the thickness of the abovementioned ascorbic acid
crystal used herein is obtained by randomly selecting 100 crystals
from a scanning electron microscope image, obtaining the thickness
of each of the selected crystals by image analysis, and obtaining
the average value thereof. Moreover, the particle shape, etc. is
obtained using a scanning electron microscope, and measured using
the particulate powder obtained in the measurement of the particle
diameter described below.
[0055] (Particle Diameter)
[0056] The average particle diameter of the abovementioned ascorbic
acid crystal is 50 to 100 .mu.m, preferably 60 to 95 .mu.m. Within
this range, the abovementioned usage characteristics are
superior.
[0057] Note that the abovementioned average particle diameter and
shape of particles are measured using the following method.
[0058] Method:
[0059] 1. Commercially available ascorbic acid crystals are infused
into acetone, and dissolved to obtain a saturated state.
[0060] 2. Fine particulate crystals of the ascorbic acid present in
the ascorbic acid saturated acetone solution of 1 are subjected to
ultracentrifugation using a generally known ultracentrifuge via a
generally known method, to precipitate and remove particles of the
ascorbic acid, thus preparing an ascorbic acid saturated acetone
solution (hereinafter, referred to as a dispersion medium) not
containing fine particulate crystals of the ascorbic acid.
[0061] 3. A small amount (5 mL) of the ascorbic acid dispersion
material of the present invention, as an analyte, is infused into
20 mL of the dispersion medium prepared in 2, lightly shaken, and
mixed.
[0062] 4. The suspension liquid of 3 is subjected to
ultracentrifugation using an ultracentrifuge under generally known
conditions, to precipitate particles of the ascorbic acid, and
remove the supernatant.
[0063] 5. 20 mL of the dispersion medium prepared in 2 is added to
the obtained precipitate, lightly shaken, and dispersed.
[0064] 6. The operations of 4 and 5 are further carried out to
remove the solvent component of the ascorbic acid dispersion
material of the present invention, following which the operation of
4 is further carried out to precipitate particles of the ascorbic
acid, and remove the supernatant, and the particles are then dried
at a low temperature to obtain particulate powder.
[0065] 7. An appropriate amount of hexane for measuring the
particle size distribution is added to the particulate powder
obtained in 6, to slightly disperse the precipitate, and obtain a
sample for particle size analysis.
[0066] 8. The sample of 7 for particle size analysis is subjected
to measurement of its laser diffraction/scattering particle
diameter distribution.
[0067] Note that it was found (not illustrated) that the particle
diameter and particle shape that are measured after grinding
commercially available ascorbic acid crystals and dispersing them
in hexane are not significantly different from the particle
diameter and particle shape which are measured using the
abovementioned method after grinding commercially available
ascorbic acid crystals. As a result, the particles extracted via
the abovementioned method are able to faithfully reproduce the
shape and particle diameter of the particles in the dispersion
material.
[0068] (Particle Size Distribution)
[0069] While the particle size distribution of the abovementioned
ascorbic acid crystal is not particularly limited, particles having
a particle diameter of 30 to 120 .mu.m account for preferably 40 to
80%, more preferably 50 to 75%, of the overall particles. Within
this range, the abovementioned usage characteristics are
superior.
[0070] Note that the abovementioned particle size distribution
refers to the value that is obtained by a laser
diffraction/scattering particle diameter distribution measurement
using the sample for particle size analysis obtained in the
abovementioned particle diameter measurement method.
[0071] (Ascorbic Acid Concentration)
[0072] While the concentration of the ascorbic acid in the ascorbic
acid dispersion material of the present invention is not
particularly limited, the ascorbic acid in the overall ascorbic
acid dispersion material is preferably 10 to 45 wt %, and more
preferably 20 to 40 wt %. Within this range, the ascorbic acid can
be effectively used at a high concentration; and in case where it
is used for cosmetics, skin care preparations, etc., the effects on
skin are superior.
[0073] Note that while the state of the ascorbic acid in the
abovementioned concentration is not particularly limited, examples
thereof may include crystal and noncrystal states, as well as the
state of being dissolved in a solvent, etc.
[0074] (Density)
[0075] While the density of the ascorbic acid dispersion material
of the present invention is not particularly limited, the average
density is preferably 1.30 to 1.40 g/cm.sup.3, and more preferably
1.31 to 1.39 g/cm.sup.3. Within this range, the ascorbic acid can
be effectively used at a high concentration; and in cases where it
is used for cosmetics, skin care preparations, etc., the
abovementioned effects and usage characteristics are superior.
[0076] Note that the abovementioned density refers to a value
measured using a dry densimeter.
[0077] (Viscosity)
[0078] While the viscosity of the ascorbic acid dispersion material
of the present invention is not particularly limited, the average
viscosity is preferably 5000 to 300000 mPas, and more preferably
8000 to 240000 mPas, from the perspectives of storage stability and
usage characteristics. Within this range, the ascorbic acid can be
effectively used at a high concentration; and in cases where it is
used for cosmetics and skin care preparations, etc., the
abovementioned usage characteristics are superior.
[0079] The abovementioned average viscosity used herein refers to a
value measured using a Brookfield rotation viscometer under
temperature conditions of 20.degree. C.
[0080] (Manufacturing Method)
[0081] While the manufacturing method for the ascorbic acid
dispersion material of the present invention is not particularly
limited, it is preferably manufactured via the manufacturing method
of the present invention, described below.
[0082] The manufacturing method of the present invention includes:
a heating step involving infusing an ascorbic acid into a solvent,
and heating the ascorbic acid to a predetermined temperature to
dissolve the ascorbic acid; a cooling step involving cooling the
solution with the ascorbic acid dissolved therein to remove the
heat of the solution; and a growth step involving storing the
solution after the completion of the abovementioned cooling step
for a predetermined period to promote crystal growth.
[0083] As a result, the ascorbic acid dispersion material of the
present invention can be more efficiently manufactured.
[0084] Below, each step will be described.
[0085] [Heating Step]
[0086] The abovementioned heating step refers to a step involving
infusing an ascorbic acid into a solvent, and heating the ascorbic
acid to a predetermined temperature to dissolve the ascorbic
acid.
[0087] While the raw material of the abovementioned ascorbic acid
is not particularly limited, for example, crystal powder of a
commercially available ascorbic acid, etc. can be used, and may be
subjected to treatment such as grinding, etc.
[0088] The abovementioned solvent is as mentioned above, and for
example, glycerin, etc., can be used.
[0089] While the method for infusing an ascorbic acid into the
abovementioned solvent is not particularly limited, it can be
carried out via methods such as a method for directly infusing the
raw material powder of the abovementioned ascorbic acid into the
abovementioned solvent.
[0090] After infusing the raw material powder of the ascorbic acid
into the abovementioned solvent, and subsequently heating it to a
predetermined temperature, the raw material powder of the ascorbic
acid is dissolved.
[0091] While the temperature of the abovementioned heating varies
based on the shape/concentration of the ascorbic acid of the raw
material, the kind of solvent, etc., the temperature of the solvent
is preferably 100 to 125.degree. C.
[0092] Moreover, the method of the abovementioned dissolution is
preferably carried out by stirring, from the perspectives of the
dissolution speed and homogeneous dispersion. Note that stirring
under the abovementioned heating temperature conditions can be
carried out via known methods. For example, it can be carried out
by heating using known heating devices, and using known stirring
machines.
[0093] Moreover, while heating in the abovementioned dissolution
varies based on the shape/concentration of the ascorbic acid of the
raw material, the kind of solvent, etc., this heating is preferably
rapidly finished after the completion of the dissolution, from the
perspectives of preventing the modification and decomposition of
the ascorbic acid due to excessive heating.
[0094] For example, in cases where the abovementioned solvent is
glycerin, the completion of the abovementioned dissolution is
determined when the color of the mixed liquid changes, becoming
transparent.
[0095] Moreover, the container for carrying out the abovementioned
dissolution is not particularly limited as long as the container is
tolerant to the solvent, the ascorbic acid, etc., and also tolerant
to the temperatures in this heating step and the cooling step
described below; for example, containers made of glass or plastic
can be used. While the shape of the abovementioned container is
also not particularly limited, general beakers and flask shapes can
be used. Moreover, the abovementioned container is preferably a
container having sealing and shading properties because storage
after manufacturing the ascorbic acid dispersion liquid of the
present invention can be carried out in the same container.
[0096] Note that, as required, the abovementioned dissolution can
be carried out in an inert gas stream such as a nitrogen gas.
[0097] [Cooling Step]
[0098] The abovementioned cooling step refers to a step involving
cooling the solution with the ascorbic acid dissolved therein, as
obtained after the abovementioned heating step, to remove heat from
the solution.
[0099] While the method of the abovementioned cooling is not
particularly limited, the cooling speed is preferably 5 to
20.degree. C./min. Such cooling can be carried out by a method
involving, after the completion of the abovementioned heating step,
immersing the container used in the abovementioned heating step
into water with the solution contained in the container. While
water used in this case is not particularly limited, tap water can
be used as is. Moreover, a sufficient amount of water is preferably
used for cooling to the temperatures described below, with the
temperature generally being preferably approximately 4 to
20.degree. C.
[0100] The removal of heat in this step is intended to set the
temperature in the internal solution to 35 to 50.degree. C.,
preferably approximately 40.degree. C.; once it reaches a
temperature within this range, the removal of heat is
completed.
[0101] [Growth Step]
[0102] The abovementioned growth step refers to a step involving
storing the solution after the abovementioned cooling step for a
predetermined period to promote crystal growth.
[0103] The abovementioned growth step can be carried out by keeping
the abovementioned solution after the abovementioned cooling step
at preferably 27 to 38.degree. C., more preferably approximately
30.degree. C.
[0104] The abovementioned growth step is carried out for a period
of 5 hours or longer, until the abovementioned crystal grows to be
the desired size (particle diameter, thickness).
[0105] While the abovementioned specific period varies depending on
the kind of solvent, the concentration of the ascorbic acid, etc.,
for example, in cases where the abovementioned solvent is glycerin,
and the ascorbic acid is 10 to 45 parts by weight in 100 parts by
weight of the total amount of the ascorbic acid and glycerin, the
abovementioned period is 3 hours or longer, and preferably half a
day or longer.
[0106] After carrying out the abovementioned growth step, the
ascorbic acid dispersion material of the present invention can be
obtained.
[0107] When the ascorbic acid dispersion material of the present
invention is manufactured as mentioned above, it is possible to
obtain the abovementioned ascorbic acid crystals in the dispersion
material of the present invention, which are not conventionally
obtained.
[0108] For example, there is a method involving heating to
dissolve, then quenching using dry ice, thereby rapidly generating
a large number of crystal cores. Because a large number of crystal
cores develop, the number of molecules available for crystal growth
decreases, and the cores grow to be crystal particles having a
small crystal particle diameter. Moreover, rapid cooling also
allows the viscosity of glycerin, which is a solvent, to rapidly
increase giving rise to a small value for the degrees of freedom in
the solution. For this reason, crystal growth tends to not occur,
and this presumably gives rise to crystals having a small particle
diameter (crystals having a smaller particle diameter than the
abovementioned ascorbic acid crystal).
[0109] In contrast, in the present invention, heat is simply
removed instead of cooling, and therefore crystal cores gradually
develop. For this reason, crystal growth can be sufficiently
promoted, and well-formed crystals can be obtained. Moreover,
because the growth step can be carried out with a high value for
the degrees of freedom in glycerin, this also allows the growth of
crystal to be sufficiently carried out, and allows a dispersion
material, in which ascorbic acid crystals having the abovementioned
characteristic crystal shape is dispersed, to be obtained.
[0110] Below, applications and usage methods for the ascorbic acid
dispersion material of the present invention are described.
[0111] (Applications)
[0112] Because the dispersion material of the ascorbic acid
according to the present invention has the abovementioned
properties, it can be used in various applications such in
cosmetics, skin care preparations, quasi drugs, drugs, storage
liquids for ascorbic acid, and food additives. Among others,
because the ascorbic acid has effects such as antioxidative action,
the generation and maintenance of collagen, and skin whitening, it
can be suitably used in cosmetics and skin care preparations.
[0113] (Usage Methods)
[0114] In cases where the ascorbic acid dispersion material of the
present invention is used in cosmetics and skin care preparations,
the ascorbic acid dispersion material of the present invention can
be used by application onto skin.
[0115] Note that in cases where the ascorbic acid dispersion
material of the present invention is used in cosmetics and skin
care preparations, the abovementioned solvent is preferably a
solvent containing glycerin, from the perspective of safety to
human body, including skin, as well as usage characteristics upon
application onto skin (stimulation aspect), etc. Moreover, in cases
where it is used in cosmetics and skin care preparations, the
preferable aspect regarding crystals of the abovementioned ascorbic
acid is as mentioned above.
[0116] (Storage)
[0117] Because redissolution starts when the ascorbic acid
dispersion material of the present invention is 25.degree. C. or
higher, it is preferably stored at 25.degree. C. or lower.
Moreover, shaded storage is preferable from the perspective of
preventing the decomposition caused by light. Moreover, nitrogen
gas, etc. is preferably enclosed, substituted, etc., and followed
by sealing and storing, in order to prevent the decomposition and
modification of the ascorbic acid due to dissolved oxygen. Such
storage enables the decomposition/modification of the ascorbic acid
to be suppressed, allowing storage for further extended periods of
time.
[0118] While the present invention is not limited to the
abovementioned embodiments, various modifications can be made
without departing from the spirit of the present invention.
[0119] For example, the ascorbic acid dispersion material of the
present invention can contain other components without departing
from the spirit of the present invention. Examples of such other
components may include useful components used for formulations such
as drugs, quasi drugs, and cosmetics, for example, ultraviolet
inhibitors, whitening agents, perfumes, etc. Moreover, the
abovementioned other components can be blended during the
abovementioned heating step to cooling step, after the completion
of the cooling step, etc., with the timing of such blending not
being particularly limited.
EXAMPLES
[0120] While not limited thereto, the present invention will be
described below in further detail using examples and comparative
examples.
Example 1
[0121] (Manufacture of the Ascorbic Acid Dispersion Material)
[0122] [Heating Step]
[0123] 38 g of an ascorbic acid raw material fine powder
(pharmacopeia, produced by DSM Nutrition) and 62 g of glycerin as a
solvent were each weighed, and infused into a conical flask made of
glass. After infusing, the mixture was heated such that the
temperature thereof reached 115.degree. C., and stirred using a
blade type stirring device. Immediately after the temperature of
the mixture reached 115.degree. C., the color of the mixed liquid
changed from yellow to transparent. As a result, the fact that the
ascorbic acid was completely dissolved was confirmed, and the
heating step was thus completed.
[0124] [Cooling Step]
[0125] The temperature in the conical flask after the completion of
the abovementioned heating step was monitored with 5 L of tap water
at a temperature of 20.degree. C., using a temperature meter, and
it was cooled until the temperature of the mixture reached
40.degree. C.
[0126] Note that the cooling period was 5 minutes.
[0127] [Growth Step]
[0128] The conical flask after the completion of the abovementioned
cooling step was sealed with a rubber plug, placed into an
incubator having a temperature of 30.degree. C., and left for 3
days to obtain the ascorbic acid dispersion material of the present
invention (hereinafter, also referred to as GAG38) having an
ascorbic acid concentration of 38 wt %.
Example 2
[0129] An ascorbic acid dispersion material of the present
invention (hereinafter, also referred to as GAG30) having an
ascorbic acid concentration of 30 wt % was obtained as in Example
1, except that 30 g of ascorbic acid raw material fine powder and
70 g of glycerin as a solvent were used in the heating step, and
the temperature retention time in the growth step was 2 days.
Example 3
[0130] An ascorbic acid dispersion material of the present
invention (hereinafter, also referred to as GAG22) having an
ascorbic acid concentration of 22 wt % was obtained as in Example
1, except that 22 g of ascorbic acid raw material fine powder and
78 g of glycerin as a solvent were used in the heating step, and
the temperature retention time in the growth step was 1 day.
[Test Example 1] Observation of the Crystals Using a Scanning
Electron Microscope
[0131] The ascorbic acid crystals contained in the ascorbic acid
dispersion material of the present invention obtained in Examples 1
to 3 were observed using a scanning electron microscope.
[0132] Note that as a control sample, crystals of commercially
available ascorbic acid were ground using a mortar, and observed
alongside.
[0133] (Preparation of Samples for the Scanning Electron
Microscope)
[0134] Samples for the scanning electron microscope were prepared
via the following method.
[0135] Method:
[0136] 1. Ascorbic acid crystals were infused into acetone, and
dissolved to obtain a saturated state.
[0137] 2. Fine particulate crystals of the ascorbic acid present in
the ascorbic acid saturated acetone solution of 1 were subjected to
ultracentrifugation using an ultracentrifuge under generally known
conditions, to precipitate and remove particles of the ascorbic
acid, thus preparing an ascorbic acid saturated acetone solution
(hereinafter, referred to as the dispersion medium) not containing
fine particulate crystals of the ascorbic acid.
[0138] 3. 5 mL of the ascorbic acid dispersion material of the
present invention obtained in Examples 1 to 3 as an analyte and 0.5
g of commercially available ascorbic acid crystal powder were both
infused into 20 mL of the dispersion medium prepared in 2, lightly
shaken, and mixed.
[0139] 4. The suspension liquid of 3 was subjected to
ultracentrifugation using an ultracentrifuge under generally known
conditions, to precipitate particles of the ascorbic acid, and
remove the supernatant.
[0140] 5. 20 mL of the dispersion medium prepared in 2 was added to
the obtained precipitate, lightly shaken, and dispersed.
[0141] 6. The operations of 4 and 5 were further carried out to
remove the solvent component of the ascorbic acid dispersion
material of the present invention, following which the operation of
4 was further carried out to precipitate particles of the ascorbic
acid, and remove the supernatant, and the particles were dried at a
low temperature to obtain particulate powder.
[0142] 7. The obtained particulate powder was used as a sample for
the scanning electron microscope.
[0143] (Observation Using a Scanning Electron Microscope)
[0144] Regarding the obtained sample for a scanning electron
microscope, an electron microscope image was acquired using a
scanning electron microscope under the following conditions, and
the acquired image was observed.
Conditions:
[0145] acceleration voltage: 10 kV
[0146] magnification: 1000 times (5000 times for the ascorbic acid
powder of the control sample)
[0147] The obtained results are shown in FIG. 1 (Example 1: GAG38),
FIG. 2 (Example 2: GAG30), FIG. 3 (Example 3: GAG22), and FIG. 4
(control testing: commercially available ascorbic acid crystal
powder).
[0148] (Measurement of the Crystal Thickness)
[0149] Further, 100 crystals were randomly selected from the
obtained scanning electron microscope image, and an image analysis
of the obtained scanning electron microscope image was carried out
to obtain the average value of the thickness of the selected
crystals. The results thereof are shown below.
[0150] Average value of the crystal thickness:
[0151] Example 1 (GAG38): 1.194 .mu.m
[0152] Example 2 (GAG30): 1.040 .mu.m
[0153] Example 3 (GAG22): 0.924 .mu.m
[0154] (Results and Remarks)
[0155] The results show that most of the ascorbic acid crystals
contained in the ascorbic acid dispersion material of the present
invention obtained in Examples 1 to 3 have a flat plate shape, have
gentle angles at the corners with few sharp angles, and have a low
thickness with small variations in thickness.
[0156] In contrast, the results show that the ascorbic acid crystal
powder, which is an object sample, has an indeterminate crystal
shape, which is totally different from the crystal shape of the
ascorbic acid contained in the ascorbic acid dispersion material of
the present invention.
[0157] Due to properties of the crystal structure, the ascorbic
acid dispersion material of the present invention is presumed to
have superior usage characteristics upon application onto skin.
[Test Example 2] Particle Size Analysis
[0158] A particle size analysis of the ascorbic acid crystals
contained in the ascorbic acid dispersion material of the present
invention obtained in Examples 1 to 3 was carried out.
[0159] (Preparation of Samples for Particle Size Analysis)
[0160] Samples for particle size analysis were prepared from the
ascorbic acid dispersion material of the present invention obtained
in Examples 1 to 3, as in Steps 1 to 6 of the method used to obtain
particulate powder in preparing samples for the scanning electron
microscope of Test Example 1, an appropriate amount of hexane for
measuring the particle size distribution was added to the
particulate powder, and the precipitate was slightly dispersed to
obtain samples for particle size analysis.
[0161] (Particle Size Analysis)
[0162] The particle size analysis of the obtained samples for
particle size analysis was carried out using a laser
diffraction/scattering particle diameter distribution measurement
device (type name: LA-950V2, manufactured by Horiba, Ltd.).
[0163] The obtained results (histogram) are shown in FIG. 5
(Example 1: GAG38), FIG. 6 (Example 2: GAG30), and FIG. 7 (Example
3: GAG22).
[0164] The results (particle diameter and frequency) are shown in
Table 1 (Example 1: GAG38), Table 2 (Example 2: GAG30), and Table 3
(Example 3: GAG22).
[0165] Moreover, the average particle diameter, the median
diameter, the mode diameter, and the ratio of particles having a
particle diameter of 30 to 120 .mu.m are shown in Table 4.
TABLE-US-00001 TABLE 1 Particle diameter Frequency Passing portion
No. (.mu.m) (%) cumulative (%) 35 1.151 0.000 0.000 36 1.318 0.000
0.000 37 1.510 0.000 0.000 38 1.729 0.000 0.000 39 1.981 0.000
0.000 40 2.269 0.000 0.000 41 2.599 0.000 0.000 42 2.978 0.000
0.000 43 3.409 0.000 0.000 44 3.905 0.000 0.000 45 4.472 0.000
0.000 46 5.122 0.000 0.000 47 5.867 0.000 0.000 48 6.720 0.108
0.108 49 7.697 0.215 0.324 50 8.816 0.397 0.721 51 10.097 0.687
1.407 52 11.568 1.138 2.546 53 13.246 1.728 4.274 54 15.172 2.402
6.676 55 17.377 3.085 9.761 56 19.904 3.729 13.490 57 22.297 4.328
17.818 58 26.111 4.892 22.709 59 29.907 5.424 28.133 60 34.255
5.925 34.088 61 39.234 6.394 40.452 62 44.938 6.797 47.250 63
51.471 7.025 54.275 64 58.953 7.008 61.281 65 67.523 8.710 67.901
66 77.339 6.162 74.153 67 88.583 5.381 79.534 68 101.460 4.506
84.040 69 116.210 3.675 87.715 70 133.103 3.114 90.829 71 152.453
2.657 93.487 72 174.616 2.185 95.672 73 200.000 1.701 97.372 74
229.075 1.252 98.624 75 282.378 0.884 99.509 76 300.518 0.491
100.000 77 344.206 0.000 100.000 78 394.244 0.000 100.000 79
451.556 0.000 100.000 80 517.200 0.000 100.000 81 592.387 0.000
100.000 82 678.504 0.000 100.000 83 777.141 0.000 100.000 84
890.115 0.000 100.000 85 1019.515 0.000 100.000
TABLE-US-00002 TABLE 2 Particle diameter Frequency Passing portion
No. (.mu.m) (%) cumulative (%) 35 1.151 0.000 0.000 36 1.318 0.000
0.000 37 1.510 0.000 0.000 38 1.729 0.000 0.000 39 1.981 0.000
0.000 40 2.269 0.000 0.000 41 2.599 0.000 0.000 42 2.976 0.000
0.000 43 3.409 0.000 0.000 44 3.905 0.000 0.000 45 4.472 0.000
0.000 46 5.122 0.000 0.000 47 5.867 0.102 0.102 48 6.720 0.180
0.282 49 7.697 0.294 0.576 50 8.816 0.442 1.019 51 10.097 0.624
1.642 52 11.565 0.839 2.481 53 13.246 1.032 3.513 54 15.172 1.168
4.681 55 17.377 1.233 5.914 56 19.904 1.256 7.171 57 22.297 1.285
8.455 58 26.111 1.370 9.825 59 29.907 1.573 11.398 60 34.255 1.986
13.384 61 39.234 2.772 15.156 62 44.938 4.109 20.265 63 51.471
5.953 25.218 64 58.953 8.048 34.266 65 67.523 9.821 44.088 66
77.339 11.253 55.341 67 88.583 11.250 66.591 68 101.460 9.604
76.195 69 116.210 7.243 83.438 70 133.103 5.418 88.856 71 152.453
4.015 92.871 72 174.616 2.883 95.754 73 200.000 1.936 97.870 74
229.075 1.219 98.889 75 262.376 0.714 99.603 76 300.518 0.397
100.000 77 344.206 0.000 100.000 78 394.244 0.000 100.000 79
451.556 0.000 100.000 80 517.200 0.000 100.000 81 592.387 0.000
100.000 82 678.504 0.000 100.000 83 777.141 0.000 100.000 84
890.118 0.000 100.000 85 1019.515 0.000 100.000
TABLE-US-00003 TABLE 3 Particle diameter Frequency Passing portion
No. (.mu.m) (%) cumulative (%) 35 1.151 0.000 0.000 36 1.318 0.000
0.000 37 1.510 0.000 0.000 38 1.729 0.000 0.000 39 1.981 0.000
0.000 40 2.269 0.000 0.000 41 2.598 0.000 0.000 42 2.976 0.000
0.000 43 3.409 0.000 0.000 44 3.905 0.000 0.000 45 4.472 0.000
0.000 46 5.122 0.000 0.000 47 5.867 0.000 0.000 48 6.720 0.119
0.119 49 7.697 0.216 0.335 50 8.816 0.363 0.698 51 10.097 0.575
1.273 52 11.565 0.874 2.147 53 13.246 1.222 3.369 54 15.172 1.569
4.938 55 17.377 1.868 6.798 56 19.904 2.073 8.871 57 22.797 2.223
11.094 58 26.111 2.347 13.441 59 29.907 2.500 15.941 60 34.255
2.747 18.688 61 39.234 3.184 21.872 62 44.938 3.900 25.772 63
51.471 4.810 30.582 64 58.953 5.815 30.397 65 67.523 6.732 43.129
66 77.339 7.514 50.643 67 88.583 7.922 58.465 68 101.460 7.408
65.873 69 116.210 6.386 72.259 70 133.103 5.656 77.815 71 152.453
4.889 82.704 72 174.616 4.263 86.967 73 200.000 3.668 90.533 74
229.075 3.057 93.690 75 262.376 2.453 98.143 76 300.518 1.895
98.038 77 344.206 1.053 99.090 78 394.244 0.585 99.675 79 451.556
0.325 100.000 80 517.200 0.000 100.000 81 592.387 0.000 100.000 82
678.504 0.000 100.000 83 777.141 0.000 100.000 84 890.116 0.000
100.000 85 1019.515 0.000 100.000
TABLE-US-00004 TABLE 4 Ratio of particles Average having a particle
particle Median Mode diameter of 30 to Analyte diameter diameter
diameter 120 .mu.m Example 1 61.99 .mu.m 47.39 .mu.m 48.19 .mu.m
53.66% (GAG38) Example 2 79.50 .mu.m 72.51 .mu.m 72.51 .mu.m 70.05%
(GAG30) Example 3 94.79 .mu.m 76.45 .mu.m 82.70 .mu.m 53.40%
(GAG22)
[0166] (Results and Remarks)
[0167] The results show that particles of the ascorbic acid
contained in the ascorbic acid dispersion material of the present
invention obtained in Examples 1 to 3 have little deviation in the
particle diameter. As a result, usage characteristics upon
application onto skin are presumed to be superior.
[Test Example 3] X-Ray Diffraction Analysis
[0168] The X-ray diffraction analysis of the ascorbic acid crystals
contained in the ascorbic acid dispersion material of the present
invention obtained in Examples 1 to 3 was carried out. Note that as
a control sample, commercially available ascorbic acid was ground
using a mortar, and tested alongside.
[0169] (Samples for X-Ray Diffraction Analysis)
[0170] As a sample for X-ray diffraction analysis, the samples for
the scanning electron microscope (particulate powder) manufactured
in Test Example 1 were used.
[0171] (X-Ray Diffraction Analysis)
[0172] The X-ray diffraction analysis of the obtained sample for
the X-ray diffraction analysis was carried out using an X-ray
diffraction analysis device (device name: XPERT-PRO MPD, produced
by PANalytical) under the following conditions.
Conditions:
[0173] scanning range: (.degree. 2.theta.): 10.000 to 30.00
[0174] target: Cu
[0175] X-ray output setting: 40 mA, 45 kV
[0176] step size (.degree. 2.theta.): 0.017
[0177] type of scanning: continuous
[0178] sample width (mm): 10.00
[0179] The obtained results are shown in FIG. 9 (Example 1: GAG38),
FIG. 10 (Example 2: GAG30), and FIG. 11 (Example 3: GAG22).
[0180] (Results and Remarks)
[0181] The results show that in the X-ray diffraction analysis, the
ascorbic acid crystals contained in the ascorbic acid dispersion
material of the present invention obtained in Examples 1 to 3
includes peaks of 20 angles at 10.6, 15.9, 16.2, 17.6, 20.0, 25.4,
27.0, 27.3 and 28.2 degrees (.+-.0.2 degrees). As a result, these
crystals have a specific crystal structure.
[Test Example 4] Viscosity Analysis
[0182] A viscosity analysis of the ascorbic acid dispersion
material of the present invention obtained in Examples 1 to 3 was
carried out.
[0183] The viscosity analysis regarding the ascorbic acid
dispersion material of the present invention obtained in Examples 1
to 2 was carried out using a Brookfield viscometer (trade name:
RVDV-I+, manufactured by BROOKFIELD) under the following
conditions.
Conditions:
[0184] temperature: 20 degrees
[0185] rotation speed: 6 r/min, after 1 minute
[0186] rotor No: No. 7
[0187] The ascorbic acid dispersion material of the present
invention obtained in Example 3 was measured using a Brookfield
viscometer (trade name: LVDV-I+, produced by BROOKFIELD) under the
following conditions.
Conditions:
[0188] temperature: 20 degrees
[0189] rotation speed: 6 r/min, after 1 minute
[0190] rotor No: No. 64
[0191] The obtained results are shown in Table 5.
TABLE-US-00005 TABLE 5 Analyte Test results Example 1 (GAG38)
210000 mPa s Example 2 (GAG30) 130000 mPa s Example 3 (GAG22) 9700
mPa s
[0192] (Results and Remarks)
[0193] The obtained results show that the ascorbic acid dispersion
material of the present invention has a higher viscosity as the
ascorbic acid concentration increases.
[0194] The results also show that the viscosity of the ascorbic
acid dispersion material of the present invention obtained in
Examples 1 to 3 is a suitable viscosity as an application agent
onto skin, etc. As a result, usage characteristics upon application
onto skin are presumed to be superior.
[Test Example 5] Density Analysis
[0195] A density analysis of the ascorbic acid dispersion material
of the present invention obtained in Examples 1 to 3 was carried
out.
[0196] Density was measured using a dry automatic densimeter (trade
name: AccuPycII, produced by Shimadzu Corporation).
[0197] The results thereof are shown in Table 6.
TABLE-US-00006 TABLE 6 Analyte Average density Example 1 (GAG38)
1.3876 g/cm.sup.3 Example 2 (GAG30) 1.3548 g/cm.sup.3 Example 3
(GAG22) 1.3260 g/cm.sup.3
[0198] (Results and Remarks)
[0199] The results show that the ascorbic acid dispersion material
of the present invention has a higher density as the ascorbic acid
concentration increases, and it is an appropriate density.
[0200] Moreover, the ascorbic acid dispersion material of the
present invention obtained in Examples 1 to 3 has superior usage
characteristics upon application onto skin, and has properties of
the density obtained by this testing, in addition to the
abovementioned properties.
[0201] The above results show that the ascorbic acid dispersion
material of the present invention has higher chemical stability,
and has superior usage characteristics, such as spreadability and
smoothness, upon application onto skin.
* * * * *