U.S. patent application number 12/280846 was filed with the patent office on 2009-03-05 for oral preparation for promoting synthesis of tissue collagen.
This patent application is currently assigned to KYOWA HAKKO KOGYO CO., LTD.. Invention is credited to Ayako Kamimura, Toshikazu Kamiya, Yoko Kawada.
Application Number | 20090062371 12/280846 |
Document ID | / |
Family ID | 38541156 |
Filed Date | 2009-03-05 |
United States Patent
Application |
20090062371 |
Kind Code |
A1 |
Kamiya; Toshikazu ; et
al. |
March 5, 2009 |
ORAL PREPARATION FOR PROMOTING SYNTHESIS OF TISSUE COLLAGEN
Abstract
An object of the present invention is to provide an oral
preparation for promoting synthesis of tissue collagen, an oral
preparation for promoting healing of skin wounds or an oral
preparation for preventing or improving skin wrinkles or sagging,
which is safe and has an excellent effect. The present invention
can provide an oral preparation for promoting synthesis of tissue
collagen, an oral preparation for promoting healing of skin wounds
or an oral preparation for preventing or improving skin wrinkles or
sagging, which comprises hydroxyproline or a salt thereof as an
active ingredient.
Inventors: |
Kamiya; Toshikazu; (Ibaraki,
JP) ; Kamimura; Ayako; (Ibaraki, JP) ; Kawada;
Yoko; (Ibaraki, JP) |
Correspondence
Address: |
FITZPATRICK CELLA HARPER & SCINTO
30 ROCKEFELLER PLAZA
NEW YORK
NY
10112
US
|
Assignee: |
KYOWA HAKKO KOGYO CO., LTD.
Chiyoda-ku, Tokyo
JP
|
Family ID: |
38541156 |
Appl. No.: |
12/280846 |
Filed: |
March 23, 2007 |
PCT Filed: |
March 23, 2007 |
PCT NO: |
PCT/JP2007/055977 |
371 Date: |
August 27, 2008 |
Current U.S.
Class: |
514/423 |
Current CPC
Class: |
A23G 3/44 20130101; C07D
207/16 20130101; A23V 2002/00 20130101; A61P 43/00 20180101; A23G
3/36 20130101; A23L 33/175 20160801; A61P 17/00 20180101; A61K
31/401 20130101; A23K 20/142 20160501; A61P 17/02 20180101; A23V
2002/00 20130101; A61P 17/18 20180101; A23V 2200/318 20130101; A23V
2250/064 20130101 |
Class at
Publication: |
514/423 |
International
Class: |
A61K 31/4015 20060101
A61K031/4015; A61P 17/02 20060101 A61P017/02 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 23, 2006 |
JP |
079921/06 |
Claims
1. An oral preparation for promoting synthesis of tissue collagen,
which comprises hydroxyproline or a salt thereof as an active
ingredient and a comestible carrier.
2. The oral preparation for promoting synthesis of collagen tissue
according to claim 1, wherein the tissue is skin.
3. A method for promoting synthesis of tissue collagen, which
comprises orally administering an effective amount of
hydroxyproline or a salt thereof.
4. A method of preparing an oral medicament for promoting synthesis
of tissue collagen comprising the steps of admixing hydroxyproline
or a salt thereof with a comestible carrier.
5. An oral preparation for promoting healing of skin wounds, which
comprises hydroxyproline or a salt thereof as an active ingredient
and a comestible carrier.
6. A method for promoting healing of skin wounds, which comprises
orally administering an effective amount of hydroxyproline or a
salt thereof.
7. A method of preparing an oral medicament for promoting healing
of skin wounds comprising the steps of admixing hydroxyproline or a
salt thereof with a comestible carrier.
8. An oral preparation for preventing or improving skin wrinkles or
sagging, which comprises hydroxyproline or a salt thereof as an
active ingredient and a comestible carrier.
9. A method for preventing or improving skin wrinkles or sagging,
which comprises orally administering an effective amount of
hydroxyproline or a salt thereof.
10. A method of preparing an oral medicament for preventing or
improving skin wrinkles or sagging comprising the steps of admixing
hydroxyproline or a salt thereof with a comestible carrier.
Description
TECHNICAL FIELD
[0001] The present invention relates to an oral preparation for
promoting synthesis of tissue collagen, an oral preparation for
promoting healing of skin wounds and an oral preparation for
preventing or improving skin wrinkles or sagging, which comprise
hydroxyproline or a salt thereof as an active ingredient.
BACKGROUND ART
[0002] Collagen is a protein which is the main component of
extracellular matrix filling the spaces between cells or groups of
cells in living tissues and is said to sometimes comprise nearly
30% of the total protein in the body of mammals (see non-patent
document No. 1).
[0003] Collagen forms a fibrous structure or a membrane structure
and its primary function is to maintain, support, bind and
reinforce the tissue structure. Collagen exists in abundance in
skin, bones, tendons, ligaments, cornea, blood vessels, etc.
Decrease and denaturation of tissue collagen is considered to be a
major factor for wrinkles, sagging skin, osteoporosis and the like
which are induced by aging of these tissues. Actually, there are
reports that tissue collagen remarkably decreases by long time
exposure to sunlight (see non-patent document No. 2) and that
lowering of metabolism of living components accompanying aging is
triggered by the lowering of metabolism of collagen (see non-patent
document No. 3).
[0004] Substances known to promote the synthesis of collagen
include TGF .beta.-1, which is a growth factor (see non-patent
document No. 4), a plant extract (see patent-document No. 1),
hydrolyzed collagen (see patent document Nos. 2 to 5) and an amino
acid composition (see patent document No. 6). More specifically,
the tripeptide Gly-Pro-Hyp is known as a sequence characteristic of
hydrolyzed collagen showing the activity to promote the synthesis
of collagen when orally ingested. However, it is also known that an
amino acid composition whose constitutive ratio of constituent
amino acids such as Gly, Pro and Hyp was made equal to that of
collagen does not show the activity to promote the synthesis of
collagen (see patent document No. 4).
[0005] On the other hand, an N-acyl derivative of hydroxyproline is
known to have the activity to promote the synthesis of collagen
when orally ingested (see non-patent document No. 4), and an
external medicine containing an N-acetyl derivative of
hydroxyproline is used as a wound-healing agent in Europe. It is
also known that hydroxyproline and an N-acyl derivative of
hydroxyproline have collagen synthesis promoting effect on cultured
human fibroblasts, and when externally applied, they have the
activity to prevent or decrease the formation of wrinkles (patent
document No. 7). However, unknown are the activity to promote the
synthesis of collagen, the activity to promote the healing of skin
wounds and the activity to prevent or improve skin wrinkles or
sagging of orally ingested hydroxyproline.
Patent document No. 1: [0006] Japanese Published Unexamined Patent
Application No. 35527/04 Patent document No. 2: [0007] Japanese
Published Unexamined Patent Application No. 278012/95 Patent
document No. 3: [0008] Japanese Published Unexamined Patent
Application No. 201649/00 Patent document No. 4: [0009] Japanese
Published Unexamined Patent Application No. 131084/01 Patent
document No. 5: [0010] Japanese Published Unexamined Patent
Application No. 137807/03 Patent document No. 6: [0011] Japanese
Published Unexamined Patent Application No. 289928/05 Patent
document No. 7: [0012] WO2000/051561 pamphlet Non-patent document
No. 1: [0013] Seikagaku Jiten (Biochemical Dictionary), First
Edition, Tokyo Kagaku Dojin, p. 480 (1984) Non-patent document No.
2: [0014] Karei to Hifu (Aging and Skin), Seishi Shoin, p. 35
(1986) Non-patent document No. 3: [0015] Mechanism and Control of
Aging, IPC, p. 151 (1993) Non-patent document No. 4: [0016]
Experimental & Molecular Pathology, Vol. 28, No. 1, p. 58-64
(1978)
DISCLOSURE OF THE INVENTION
Problems to be Solved by the Invention
[0017] An object of the present invention is to provide an oral
preparation for promoting synthesis of tissue collagen, an oral
preparation for promoting healing of skin wounds or an oral
preparation for preventing or improving skin wrinkles or sagging,
which is safe and has an excellent effect.
Means for Solving the Problems
[0018] The present invention relates to the following (1) to (10).
[0019] (1) An oral preparation for promoting synthesis of tissue
collagen, which comprises hydroxyproline or a salt thereof as an
active ingredient. [0020] (2) The oral preparation for promoting
synthesis of collagen according to the above (1), wherein the
tissue is skin. [0021] (3) A method for promoting synthesis of
tissue collagen, which comprises orally administering an effective
amount of hydroxyproline or a salt thereof. [0022] (4) Use of
hydroxyproline or a salt thereof for the manufacture of an oral
preparation for promoting synthesis of tissue collagen. [0023] (5)
An oral preparation for promoting healing of skin wounds, which
comprises hydroxyproline or a salt thereof as an active ingredient.
[0024] (6) A method for promoting healing of skin wounds, which
comprises orally administering an effective amount of
hydroxyproline or a salt thereof. [0025] (7) Use of hydroxyproline
or a salt thereof for the manufacture of an oral preparation for
promoting healing of skin wounds. [0026] (8) An oral preparation
for preventing or improving skin wrinkles or sagging, which
comprises hydroxyproline or a salt thereof as an active ingredient.
[0027] (9) A method for preventing or improving skin wrinkles or
sagging, which comprises orally administering an effective amount
of hydroxyproline or a salt thereof. [0028] (10) Use of
hydroxyproline or a salt thereof for the manufacture of an oral
preparation for preventing or improving skin wrinkles or
sagging.
EFFECT OF THE INVENTION
[0029] The present invention provides an oral preparation for
promoting synthesis of tissue collagen, an oral preparation for
promoting healing of skin wounds or an oral preparation for
preventing or improving skin wrinkles or sagging, comprising
hydroxyproline or a salt thereof as an active ingredient, which is
safe and has an excellent effect.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] FIG. 1 is a graph showing the concentration of free
hydroxyproline in serum after oral intake of hydroxyproline.
[0031] FIG. 2 is a graph showing the concentration of free
hydroxyproline in the skin after oral intake of hydroxyproline.
BEST MODES FOR CARRYING OUT THE INVENTION
[0032] Hydroxyproline used in the present invention may be any of
the stereoisomers of hydroxyproline. That is, hydroxyproline can
exist as eight kinds of stereoisomers according to whether proline
is in the D or L form, whether the hydroxyl group is located at the
3- or 4-position, and whether the stereoisomer is in the cis or
trans form, and any of these stereoisomers can be employed in the
present invention.
[0033] Specifically, hydroxyproline includes
cis-4-hydroxy-L-proline, cis-4-hydroxy-D-proline,
cis-3-hydroxy-L-proline, cis-3-hydroxy-D-proline,
trans-4-hydroxy-L-proline, trans-4-hydroxy-D-proline,
trans-3-hydroxy-L-proline and trans-3-hydroxy-D-proline.
[0034] Hydroxyproline is a kind of amino acid which exists widely
in nature as the major amino acid component of collagen and as a
constituent amino acid of elastin, and can be produced, for
example, by acid hydrolysis of collagen derived from animals such
as pig and cow, followed by purification by ordinary means.
[0035] Trans-4-hydroxy-L-proline can be produced by using proline
4-hydroxylase isolated from a microorganism belonging to the genus
Amycolatopsis or Dactylosporangium (Japanese Published Unexamined
Patent Application No. 313179/95). Cis-3-hydroxy-L-proline can be
produced by using praline 3-hydroxylase isolated from a
microorganism belonging to the genus Streptomyces (Japanese
Published Unexamined Patent Application No. 322885/95)
[Bioindustry, Vol. 14, No. 31 (1997)].
[0036] The above hydroxyprolines produced by using enzymes derived
from microorganisms are superior in quality and are preferred as
hydroxyproline used in the present invention.
[0037] The salts of hydroxyproline include acid addition salts,
metal salts, ammonium salts, organic amine addition salts and amino
acid addition salts.
[0038] Examples of the acid addition salts include inorganic acid
addition salts such as hydrochloride, sulfate, nitrate and
phosphate, and organic acid addition salts such as acetate,
maleate, fumarate, citrate, malate, lactate, .alpha.-ketoglutarate,
gluconate and caprylate.
[0039] Examples of the metal salts are alkali metal salts such as
sodium salt and potassium salt, alkaline earth metal salts such as
magnesium salt and calcium salt, aluminum salt and zinc salt.
[0040] Examples of the ammonium salts are ammonium salt and
tetramethylammonium salt.
[0041] Examples of the organic amine addition salts are salts with
morpholine and piperidine.
[0042] Examples of the amino acid addition salts are salts with
glycine, phenylalanine, lysine, aspartic acid and glutamic
acid.
[0043] The oral preparation for promoting synthesis of tissue
collagen, the oral preparation for promoting healing of skin wounds
or the oral preparation for preventing or improving skin wrinkles
or sagging of the present invention comprises hydroxyproline or a
salt thereof, and if necessary, may comprise one or more kinds of
pharmaceutically acceptable carriers, and further, active
ingredients for other treatments.
[0044] The oral preparation for promoting synthesis of tissue
collagen, the oral preparation for promoting healing of skin wounds
or the oral preparation for preventing or improving skin wrinkles
or sagging of the present invention can be produced according to
arbitrary methods well known in the technical field of
pharmaceutics by mixing hydroxyproline or a salt thereof with
carriers according to need.
[0045] In preparing the oral preparation for promoting synthesis of
tissue collagen, the oral preparation for promoting healing of skin
wounds or the oral preparation for preventing or improving skin
wrinkles or sagging of the present invention, additives such as
excipients, binders, disintegrating agents, lubricants,
dispersants, suspending agents, emulsifiers, diluents, buffers,
antioxidants and bacterial inhibitors can be used.
[0046] The agent of the present invention can be in preparation
forms such as tablets, powders, granules, emulsions, syrups and
capsules.
[0047] When the preparation form is a liquid preparation such as
syrup, the preparation can be prepared by adding water, sugars
(e.g., sucrose, sorbitol and fructose), glycols (e.g., polyethylene
glycol and propylene glycol), oils (e.g., sesame oil, olive oil and
soybean oil), antiseptics (e.g., p-hydroxybenzoates), flavors
(e.g., strawberry flavor and peppermint), and the like.
[0048] In the case of tablets, powders, granules, etc. suitable for
oral administration, they can be prepared by adding excipients such
as sugars (e.g., lactose, white sugar, glucose, sucrose, mannitol
and sorbitol), starch (e.g., potato starch, wheat starch and corn
starch), inorganic substances (e.g., calcium carbonate, calcium
sulfate, sodium hydrogencarbonate and sodium chloride) and plant
powders (e.g., licorice powder and gentian powder), disintegrating
agents such as starch, agar, gelatin powder, crystalline cellulose,
carmellose sodium, carmellose calcium, calcium carbonate, sodium
hydrogencarbonate and sodium alginate, lubricants such as magnesium
stearate, talc, hydrogenated vegetable oil, macrogol and silicone
oil, binders such as polyvinyl alcohol, hydroxypropyl cellulose,
methyl cellulose, ethyl cellulose, carmellose, gelatin and starch
paste, surfactants such as fatty acid esters, plasticizers such as
glycerin, and the like.
[0049] The preparations suitable for oral administration may also
comprise additives generally used in foods and drinks such as
sweeteners, coloring agents, preservatives, thickening stabilizers,
antioxidants, color developers, bleaching agents, fungicides, gum
bases, bitter agents, enzymes, glazing agents, sour agents,
seasonings, emulsifiers, nutrient supplements, manufacture
facilitating agents, flavors and spice extracts.
[0050] The preparations suitable for oral administration may be
used as such, or in any of the forms such as powder foods,
sheet-shaped foods, bottled foods, canned foods, retort pouched
foods, capsule foods, tablet foods, liquid foods and health drinks,
and may also be used as foods and drinks such as health foods,
functional foods, food supplements and foods for specified health
uses for promoting synthesis of tissue collagen, promoting healing
of skin wounds, or preventing or improving skin wrinkles or
sagging.
[0051] The concentration of hydroxyproline or a salt thereof in the
oral preparation of the present invention is appropriately selected
depending upon the kind of the oral preparation, the effect
expected by the administration of the oral preparation, etc., but
it is usually 0.1 to 100% by weight, preferably 0.5 to 70% by
weight, particularly preferably 1 to 50% by weight in terms of
hydroxyproline or a salt thereof.
[0052] The dose of the oral preparation of the present invention
varies depending upon the administration route, the age and body
weight of a subject of administration, etc. Usually, the agent is
administered in a dose of 5 to 5000 mg, preferably 50 to 5000 mg,
more preferably 500 to 5000 mg per day for an adult in terms of
hydroxyproline or a salt thereof at once or in several portions.
There is no specific restriction as to the period of
administration, but it is usually one day to one year, preferably
one week to three months.
[0053] The oral preparation of the present invention can be used
not only for humans but also for animals other than humans
(hereinafter abbreviated as nonhuman animals).
[0054] Nonhuman animals include animals other than humans such as
mammals, birds, reptiles, amphibians and fish.
[0055] In the case of administration to a nonhuman animal, the dose
varies depending upon the age and kind of the animal, etc. Usually,
the agent is administered once or several times per day in a daily
dose of 0.1 to 100 mg, preferably 1 to 100 mg, more preferably 10
to 100 mg per kg of body weight in terms of hydroxyproline or a
salt thereof.
[0056] There is no specific restriction as to the period of
administration, but it is usually one day to one year, preferably
one week to three months.
[0057] The effect of hydroxyproline on promotion of the synthesis
of collagen in the skin, promotion of wound-healing and improvement
of skin wrinkles or sagging was examined and the results are shown
in the following test examples.
TEST EXAMPLE 1
[0058] HOS:HR-1 mouse (seven-week-old female; purchased from Japan
SLC, Inc.) was used in the test.
[0059] Trans-4-hydroxy-L-proline (Kyowa Hakko Kogyo Co., Ltd.;
hereinafter referred to as hydroxyproline) was dissolved in
purified water at a concentration of 50 mg/ml, and the resulting
solution was orally administered in an amount of 500 mg/kg. After
0.5, 1, 2, 4, 6 and 24 hours, blood was collected from the
abdominal vena cava of the mouse under diethyl ether inhalation
anesthesia to obtain a serum. After cervical dislocation, dorsal
skin was collected, subjected to freeze-disruption and then to
extraction with water to obtain a skin extract.
[0060] The amount of hydroxyproline in the sera and the skin
extract was analyzed by high performance liquid chromatography
using ODS column (4.6 cm.phi..times.15 cm, GL Sciences Inc.) after
protein was removed with an equal amount of 2% (w/v) sulfosalicylic
acid and the second amino group was labeled with NBD-Cl
(4-chloro-7-nitro-2,1,3-benzoxadiazole, Tokyo Chemical Industry
Co., Ltd.).
[0061] The results are shown in FIGS. 1 and 2. It was revealed that
the orally ingested hydroxyproline quickly moves into blood and
skin.
TEST EXAMPLE 2
[0062] F344/DuCrlCrlj rats (12 heads, 29-week-old male; purchased
from Charles River Laboratories Japan, Inc.) were divided into 2
groups each consisting of 6 rats.
[0063] The rats of Group 1 and Group 2 were fed with the feed of
Example 5 and the control feed of Comparative Example 1,
respectively, ad libitum for 7 days. The abdominal area of each rat
was shaved with clippers under anesthesia by intraperitoneal
administration of pentobarbital, and cut sponge pieces (ca. 150 mg,
2 mm thick, ca. 38 mm.times.12 mm; Ivalon, Inc.) were inserted into
two spots under the skin, followed by suturing. After further
feeding for 7 days, the sponge pieces were taken out.
[0064] The sponge pieces were subjected to reaction using 6N
hydrochloric acid (20 ml/piece) at 110.degree. C. for 18 hours to
decompose them with acid and heat. The products obtained by
decomposition with acid and heat were diluted 10 times with 1M
borate buffer (pH 10.6), and the amount of hydroxyproline was
measured in the same manner as in Test Example 1 and was regarded
as an index of the collagen-synthesizing ability and
tissue-restoring ability of a rat.
[0065] The values were shown in terms of average value.+-.standard
deviation and a test of statistical significance was performed by
Student's t-test.
TABLE-US-00001 TABLE 1 Amount of hydroxyproline/ Significance by
amount of sponge (.mu.g/g) 2 sample t-test Group 1 4854.1 .+-.
1340.8 p < 0.05 Group 2 2643.6 .+-. 1105.4
[0066] The results are shown in Table 1. From the fact that the
amount of hydroxyproline derived from heat-decomposed collagen was
significantly increased in the rats of Group 1 which received
hydroxyproline, it was revealed that the synthesis of collagen in
the skin was promoted, and as a result, restoration of tissues,
that is, wound-healing, was promoted.
TEST EXAMPLE 3
[0067] Females aged 47 to 65 years (21 subjects) who chronically
suffer from dry skin and rough skin were divided into two groups.
After a 2-week observation period, Group 1 (9 subjects) and Group 2
(12 subjects) ingested hard capsules of Example 6 and hard capsules
of Comparative Example 2, respectively, for 4 weeks (2 capsules
each morning and evening). The test was carried out by
parallel-group double-blind test. At the start and the end of the
period of ingesting hard capsules, the following questions 1 to 3
were addressed to the subjects (answer "1": level 1, answer "10":
level 10) and the skin conditions of the subjects were evaluated by
a 10-level rating system. [0068] Question 1: Evaluate the level of
wrinkles on your face. [0069] 1: Wrinkles all over the surface
[0070] 10: No wrinkles [0071] Question 2: Evaluate the elasticity
of the skin of your face. [0072] 1: No elasticity [0073] 10:
Extreme elasticity [0074] Question 3: Evaluate the firmness of the
skin of your face. [0075] 1: No firmness [0076] 10: Good
firmness
[0077] In the above evaluation, a higher level indicates that a
subject feels that the skin wrinkles were more improved in Question
1 and that the elasticity and firmness associated with skin sagging
were more enhanced in Questions 2 and 3, respectively. The
improvement rate (%) was calculated according to Equation 1.
Improvement rate (%)=average value of levels after intake/average
value of levels before intake.times.100 [Equation 1]
[0078] The obtained results are shown in Table 2. The values in the
table are the average values.
TABLE-US-00002 TABLE 2 Before intake After intake Improvement
Question Subject (level) (level) rate (%) Question 1 Group 1 5.33
6.44 120.8 Level of Group 2 5.33 5.25 98.4 wrinkles Question 2
Group 1 4.67 6.89 147.6 Skin Group 2 5.67 5.33 94.1 elasticity
Question 3 Group 1 4.56 6.44 141.5 Skin Group 2 4.08 5.17 126.5
firmness
[0079] From Table 2, it was revealed that wrinkles and sagging of
the face are improved by ingesting trans-4-hydroxy-L-proline.
[0080] From the above test examples, it was indicated that orally
ingested hydroxyproline moves to the skin and exhibits the effects
of promoting synthesis of collagen, healing wounds and improving
skin wrinkles or sagging.
[0081] Certain embodiments of the present invention are illustrated
in the following examples.
EXAMPLE 1
Preparation of Tablets Comprising Hydroxyproline
[0082] Tablets comprising trans-4-hydroxy-L-proline are prepared
according to an ordinary method. That is, the following ingredients
are uniformly mixed and the resulting mixture is tabletted using a
single tablet press to obtain tablets for promoting synthesis of
tissue collagen (diameter, 5 mm; weight, 15 mg).
TABLE-US-00003 TABLE 3 Ingredient Amount (g)
Trans-4-hydroxy-L-proline 10.0 Lactose 90.0 Dry corn starch 2.0
Talc 1.8 Magnesium stearate 0.2
EXAMPLE 2
Preparation of Granules Comprising Hydroxyproline
[0083] The tablets obtained in Example 1 are ground, granulated and
sieved to obtain granules for promoting healing of skin wounds (20
to 50 mesh).
EXAMPLE 3
Preparation of a Drink Comprising Hydroxyproline
[0084] A drink for promoting synthesis of tissue collagen
comprising trans-4-hydroxy-L-proline is prepared by uniformly
dissolving the following ingredients with stirring and adding
purified water to make a total volume of 1000 ml. "Appropriate
amount" in the following table refers to an amount used for
preparing an ordinary drink in respect of flavor and pigment and
refers to an amount necessary to make a total volume of 1000 ml by
addition of purified water to the remaining ingredients in respect
of purified water.
TABLE-US-00004 TABLE 4 Ingredient Amount (g)
Trans-4-hydroxy-L-proline 5.0 Sodium benzoate 1.0 Fructose 10.0
Flavor appropriate amount Pigment appropriate amount Purified water
appropriate amount
EXAMPLE 4
Preparation of Candies Comprising Hydroxyproline
[0085] Candies for promoting healing of skin wounds comprising
trans-4-hydroxy-L-proline which are composed of the following
ingredients are prepared according to an ordinary method.
TABLE-US-00005 TABLE 5 Ingredient Amount (g)
N-Acetyl-trans-4-hydroxy-L-proline 1.00 Sorbitol powder 98.75
Flavor 0.20 Sorbitol seed 0.05
EXAMPLE 5
Preparation of a Feed for Animals Comprising Hydroxyproline
[0086] A feed for animals comprising trans-4-hydroxy-L-proline
which is composed of the following ingredients was prepared
according to an ordinary method.
TABLE-US-00006 TABLE 6 Ingredient Amount (g)
Trans-4-hydroxy-L-proline 1.0 Casein 25.0 Sucrose 40.2 Cellulose
5.0 Choline bitartrate 0.2 DL-Methionine 0.4 L-Aspartic acid 6.7
Corn starch 12.0 Corn oil 5.0 AIN76 vitamin mix 3.5 (No choline
added) AIN76 mineral mix 3.5
EXAMPLE 6
Preparation of Capsules Containing Hydroxyproline
[0087] The following ingredients were weighed, put into a mixer and
sufficiently mixed to obtain a uniform mixture. The mixture was
encapsulated in hard gelatin capsules according to an ordinary
method to obtain hard capsules containing trans-4-hydroxy-L-proline
(ca. 500 mg/capsule).
TABLE-US-00007 TABLE 7 Ingredient Amount (mg)
Trans-4-hydroxy-L-proline 500.0 Microcrystalline cellulose 97.5
Colloidal silicon dioxide 12.5 Magnesium stearate 12.5
COMPARATIVE EXAMPLE 1
[0088] A feed for animals was prepared using L-aspartic acid in
place of trans-4-hydroxy-L-proline of Example 5.
COMPARATIVE EXAMPLE 2
[0089] Hard capsules were prepared using corn starch in place of
trans-4-hydroxy-L-proline of Example 6.
INDUSTRIAL APPLICABILITY
[0090] The present invention can provide an oral preparation for
promoting synthesis of tissue collagen, an oral preparation for
promoting healing of skin wounds or an oral preparation for
preventing or improving skin wrinkles or sagging, which comprises
hydroxyproline or a salt thereof as an active ingredient.
* * * * *