JP2004217655A - Skin-whitening composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a composition (a skin-whitening agent) for skin-whitening, prophylaxis and/or treatment of pigmentation which exhibits an excellent effect on pigmentation such as blotches, freckles, tanned skin, dark skin, and dermal staining by a drug such as a steroid. <P>SOLUTION: (1) This composition comprises (i) tranexamic acid or its salt and (ii) L-cysteine, its derivative or their salt (preferably tranexamic acid and L-cysteine). (2) The composition comprises (i) tranexamic acid or its salt, (ii) L-cysteine, its derivative or their salt, and (iii) L-ascorbic acid, its derivative or their salt (preferably tranexamic acid, L-cysteine, and L-ascorbic acid). <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

  The present invention relates to novel compositions, and more particularly to whitening compositions (whitening agents).

Pigmentation, such as spots, freckles, sunburn, skin melanosis caused by drugs such as dark skin and steroids, is caused by excessive deposition of melanin pigment on the skin. In cytoplasmic granule melanosomes in melanocytes, tyrosine is oxidized by tyrosinase, dopa and dopaquinone are biosynthesized, and dopaquinone is converted to indolequinone and the like by autoxidation with ultraviolet light, and melanin is biosynthesized through a complex pathway. It has been known. Such pigmentation is cosmetically undesirable, especially for women.
Conventionally, L-ascorbic acid and its derivatives (see Patent Document 1), kojic acid (see Patent Document 2), L-cysteine (see Patent Document 3), Arbutin (see Patent Literature 4), Arctostaphylos va-ursi, an extract thereof (see Patent Literature 5), and a mixture of tranexamic acid and ascorbic acid (Patent Literature 6) are known.
However, the above is not always satisfactory in terms of its effects and the like.

JP-A-49-86554 JP-A-53-3538 JP-A-59-128320 JP-A-60-56912 JP-A-6-166609 JP-A-4-243825

  The present invention provides a whitening composition (whitening agent) and a whitening method that are more effective.

  The present inventors have conducted intensive studies and as a result, have newly found that when tranexamic acid or a salt thereof and L-cysteine, a derivative thereof or a salt thereof are used in combination, an excellent whitening effect is exhibited, and the present invention has been completed. did.

That is, the present invention relates to the following.
(1) A composition containing (i) tranexamic acid or a salt thereof, and (ii) L-cysteine, a derivative thereof, or a salt thereof.
(2) A composition containing (i) 50 to 2500 mg of tranexamic acid or a salt thereof, and (ii) 30 to 750 mg of L-cysteine, a derivative thereof or a salt thereof as a daily administration (dose) amount.
(3) A composition containing tranexamic acid and L-cysteine.
(4) A composition containing 50 to 2500 mg of tranexamic acid and 30 to 750 mg of L-cysteine as daily administration (dose) amounts.
(5) A composition containing (i) tranexamic acid or a salt thereof, (ii) L-cysteine, a derivative or a salt thereof, and (iii) L-ascorbic acid, a derivative thereof or a salt thereof.
(6) As daily doses (dose), (i) 50 to 2500 mg of tranexamic acid or a salt thereof, (ii) 30 to 750 mg of L-cysteine, a derivative thereof or a salt thereof, and (iii) L- A composition containing 50 to 3000 mg of ascorbic acid, a derivative thereof, or a salt thereof.
(7) A composition containing tranexamic acid, L-cysteine and L-ascorbic acid.
(8) A composition containing 50 to 2500 mg of tranexamic acid, 30 to 750 mg of L-cysteine, and 50 to 3000 mg of L-ascorbic acid as daily doses (dose).
(9) The composition according to any one of the above (1) to (8), which is used for whitening.
(10) The composition according to any one of the above (1) to (8), which is used for prevention and / or treatment of pigmentation disease.
(11) The composition according to any one of the above (1) to (10), wherein the dosage form is a preparation for oral administration.
(12) A whitening method comprising administering (i) tranexamic acid or a salt thereof, and (ii) L-cysteine, a derivative thereof, or a salt thereof.
(13) whitening characterized by administering (i) tranexamic acid or a salt thereof, (ii) L-cysteine, a derivative or a salt thereof, and (iii) L-ascorbic acid, a derivative or a salt thereof. Method.
(14) A method for treating pigmentation, which comprises administering (i) tranexamic acid or a salt thereof, and (ii) L-cysteine, a derivative thereof, or a salt thereof.
(15) A dye characterized by administering (i) tranexamic acid or a salt thereof, (ii) L-cysteine, a derivative or a salt thereof, and (iii) L-ascorbic acid, a derivative or a salt thereof. How to treat deposits.

  The composition of the present invention exhibited an excellent melanin pigmentation inhibitory effect as described in Examples below. Therefore, the composition of the present invention can be used as a whitening composition (whitening agent), and for preventing and / or preventing pigmentation such as skin melanosis caused by drugs such as spots, freckles, sunburn, darkening and steroids. Or it is useful as a therapeutic composition.

  The tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) or a salt thereof according to the present invention is a known compound, and as a method for obtaining the compound, a commercially available product may be used, or the compound is produced based on a known method. You can also. Examples of tranexamic acid salts include mineral salts such as hydrochloride, nitrate and sulfate, organic acid salts such as methanesulfonate, alkali metal salts such as sodium salt, potassium salt, calcium salt and magnesium salt, and alkaline earth salts. Metal salts and the like can be mentioned. In the present invention, tranexamic acid or a salt thereof is preferably tranexamic acid.

  In addition, L-cysteine, a derivative thereof, or a salt thereof according to the present invention is also a known compound, and as a method for obtaining the compound, a commercially available product may be used, or it may be produced based on a known method. Examples of L-cysteine derivatives include N-acetyl-L-cysteine, L-homocysteine, L-cysteic acid, L-homocysteic acid, L-cysteine sulfinic acid, S-sulfino-L-cysteine, and S-sulfo- L-cysteine, cystine (cysteine dimer) and the like can be mentioned. Examples of salts of L-cysteine and its derivatives include mineral salts such as hydrochloride, nitrate and sulfate, alkali metal salts such as sodium salt, potassium salt, calcium salt and magnesium salt, and alkaline earth metal salts. Can be mentioned. In the present invention, L-cysteine, a derivative thereof or a salt thereof is preferably L-cysteine.

  The L-ascorbic acid, a derivative thereof, or a salt thereof according to the present invention is also a known compound, and a commercially available product may be used as a method for obtaining the compound, or it may be produced based on a known method. Examples of the salts of L-ascorbic acid and its derivatives include mineral salts such as hydrochloride, nitrate and sulfate, alkali metal salts such as sodium salt, potassium salt, calcium salt and magnesium salt, and alkaline earth metal salts. be able to. L-ascorbic acid, its derivatives or salts thereof include L-ascorbic acid; L-ascorbates such as sodium L-ascorbate, magnesium L-ascorbate, potassium L-ascorbate and calcium L-ascorbate; Monoalkyl or monoalkenyl esters of ascorbate such as L-ascorbic acid monostearate, L-ascorbic acid monopalmitate and L-ascorbic acid monooleate; L-ascorbic acid distearate, L-ascorbic acid dipalmitate, L-ascorbic acid dioleate Dialkyl or dialkenyl esters of L-ascorbic acid such as L-ascorbic acid tristearate, L-ascorbic acid tripalmitate, L-ascorbic acid trioleate and the like; L-ascorbyl sulfates such as L-ascorbyl sulfate, sodium L-ascorbyl sulfate, potassium L-ascorbyl sulfate, magnesium L-ascorbyl sulfate and calcium L-ascorbyl sulfate; L-ascorbic acid phosphates such as ascorbyl phosphate, sodium L-ascorbyl phosphate, potassium L-ascorbyl phosphate, magnesium L-ascorbyl phosphate and calcium L-ascorbyl phosphate; ascorbic acid such as glycoside L-ascorbate Glycosides and the like can be mentioned. In the present invention, L-ascorbic acid is preferable as L-ascorbic acid, a derivative thereof or a salt thereof.

  The composition for whitening of the present invention (whitening agent) is useful for those who aim at prevention and / or treatment of pigmentation such as melanosis of the skin due to drugs such as spots, freckles, sunburn, dark skin and steroids. To be administered.

The composition of the present invention may further contain a known component having a whitening effect or a component for enhancing the whitening effect. These components include, for example, pantothenic acid, derivatives thereof or salts thereof (pantothenic acid; pantothenates such as sodium pantothenate and calcium pantothenate; pantethein, pantethine, phosphopantethein, etc.) hydroquinone or derivatives thereof (hydroquinone; Hydroquinone-glucosides such as hydroquinone-β-D-glucose (arbutin); glucosamine or derivatives thereof (glucosamine; glucosamine esters such as acetylglucosamine; glucosamine ethers such as glucosamine methyl ether); hinokitiol or derivatives thereof ( Hinokitiol; hinokitiol glycosides such as hinokitiol glucoside, etc., azelaic acid, derivatives thereof or salts thereof (azelaic acid; monoalkyl azelaic acid) Azelaic acid monoesters such as stele; azelaic acid diesters such as azelaic acid dialkyl ester, etc.), tocopherols (α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, etc.), and tocotrienols (α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, etc., ubiquinones (coenzyme Q ₆ (CoQ ₆ ), coenzyme Q ₇ (CoQ ₇ ), coenzyme Q ₈ (CoQ ₈ ), coenzyme Q ₉ (CoQ ₉ ), coenzyme Q ₁₀ (CoQ ₁₀ ), carotene (carotene, lutein, violaxanthin, spiriroxanthine, spheroidene, etc.), flavones (flavone, apigenin, luteolin and glycosides thereof) , Isoflavones or derivatives thereof (isoflavones; isoflavone glycosides, etc.), flavanones or derivatives thereof (naringenin, eriodictyol, naringin, etc.), catechins (catechin, catechin gallate, gallocatechin, etc.), flavonols (kaempferol, quercetin) Glycyrrhizic acid, a derivative thereof or a salt thereof (glycyrrhizic acid; dipotassium glycyrrhizinate, glycyrrhizic acid salt of monoammonium glycyrrhizinate, etc.), glycyrrhetinic acid, a derivative or salt thereof ( Glycyrrhetinic acid; alkyl esters of glycyrrhizic acid such as stearyl glycyrrhetinic acid, etc.), kojic acid, derivatives thereof and salts thereof (kojic acid; kojic acid monobutyrate, kojic acid) Monoalkyl esters of kojic acid such as nokaplate, kojic acid monopalmitate, kojic acid monostearate; kojic acid dialkyl esters such as kojic acid dibutyrate, kojic acid dipalmitate, kojic acid distearate, kojic acid dioleate, etc.), ellagic acid , A derivative thereof or a salt thereof (ellagic acid; ellagic acid ethers such as ellagic acid tetramethyl ether; ellagic acid derivatives such as ellagic acid tetraacetate and ellagic acid tetrabenzoate); glutathione; Salts (glutathione; S-acyl glutathiones such as S-lactoyl glutathione; N, S-diacyl glutathione diesters such as N, S-dioctanoyl glutathione distearyl, N, S-dipalmitoyl glutathione dicetyl and the like) , Resorcinol or derivatives thereof (resorcinol; alkylated resorcinols such as 4-n-butyl resorcinol, 4-isoamyl resorcinol, 4-cyclohexyl resorcinol, 5-methyl resorcinol; halogenated resorcinols such as 4-chlororesorcinol and 4-bromoresorcinol; ), Glycogen, yoquinin or an extract thereof, hamamelis or an extract thereof, saxifrage or an extract thereof, giltfish or an extract thereof, tea or an extract thereof, knotweed or an extract thereof, melissa or an extract thereof, thyme or an extract thereof Thing, sagebill or its extract, yarrow or its extract, hypericum or its extract, St. John's wort or its extract, peonies or its extract, Button or its extract, licorice or its extract, licorice or its extract, mulberry or its extract, magua or its extract, shimagua or its extract, Clara or its extract, ouaurushi or its extract, Herayahaz Or an extract thereof, a haramiji or an extract thereof, a pheasant or an extract thereof, a cyperus or an extract thereof, a mustard or an extract thereof, a dulse or an extract thereof, a willow moku (Obamoku) or an extract thereof, an ezononekomoku or an extract thereof, Fushijimoku or an extract thereof, Ishimozuku or an extract thereof, moss mushroom or an extract thereof, Kamoenoke or an extract thereof, lavender or an extract thereof, spinach or an extract thereof, barley or an extract thereof, iwanashi or an extract thereof, Merikai pear or its extract, passion flower or its extract, Kudamonotokei or its extract, water lemon or its extract, Passiflora or its extract, Moon leaf Nishiban lotus or its extract, Snake Wisteria or its extract, Keppei Nishiban lotus or its extract, wild pansy or its extract, fragrant violet or its extract, violet or its extract, cosme or its extract, Noji violet or its extract, gnosum or its extract, Tsukushi violet or The extract, white violet or its extract, Ezonotachi violet or its extract, Nepal violet or its extract, White violet or its extract, Maruba violet or its extract, Japanese violet or its extract, Purple violet or its extract , Ground grass or an extract thereof, violet saicin or an extract thereof, Tubosum violet or an extract thereof, Eisen sen or an extract thereof, tessen or an extract thereof, Kazaguruma or an extract thereof, sensin or an extract thereof, Tochu or the Extract, Togeminomasaki or its extract, Tribana or its extract, Asparagus or its extract, Ibukitranoo or its extract, Pea or its extract, Aget or its extract, Ougon or its extract, Ononis or Its extract, raspberry or its extract, jinjin or its extract, keito or its extract, okahi or its extract, saishin or its extract, hawthorn or its extract, sampens or its extract, Shirahuri or its extract Thing, Sempukuka or Is its extract, soybean ash or its extract, soybean or its extract, tea or its extract, oyster extract, molasses or its extract, juniper or its extract, beech tree or its extract, grape seed or its extract Thing, flow de manita or its extract, hop or its extract, Maikaika or its extract, Mokka or its extract, Arhat fruit or its extract, Aloe or its extract, Altea or its extract, Arnica or its extract Thing, Ashitaba or its extract, clingboard or its extract, nettle or its extract, turmeric or its extract, oak or its extract, chamomile or its extract, Kingfisher or its extract, watercress or its extract, Comfrey or its extract, salvia or Extract, radish or its extract, perilla or its extract, birch or its extract, calendula or its extract, elderberry or its extract, asparagus or its extract, mukuroji or its extract, astragalus or its Extract, mugwort or extract thereof, eucalyptus or extract thereof, noibara or extract thereof, ginkgo or extract thereof, yashajitsu or extract thereof, dickopi or extract thereof, micromelum minutum or extract thereof, Micromelum pubescens or its extract, bamboo shoot or its extract, bouka or its extract, sparrow or its extract, raspberry or its extract, syllium or its extract It can be exemplified placenta extract, etc., but should not be limited only to those described above. One of these components may be blended, or two or more of these components may be blended. In the present invention, among the above-mentioned components, L-ascorbic acid, a derivative thereof, or a salt thereof is preferable, and L-ascorbic acid is particularly preferable. The composition for whitening (whitening agent) of the present invention may further contain components other than known components having a whitening effect and components that enhance the whitening effect.

  The composition of the present invention may be administered orally or parenterally. Examples of the preparation for oral administration (oral administration preparation) include dosage forms such as tablets, capsules, powders, fine granules, liquids, troches and jellies. Preparations for parenteral administration (parenteral preparations) include extracts, plasters, alcoholic beverages, suppositories, suspensions, tinctures, ointments, cataplasms, liniments, lotions, aerosols, Examples of the dosage form include eye drops and injections, and examples of parenteral preparations include extracts, plasters, spirits, suspensions, tinctures, ointments, cataplasms, liniments, and lotions. And a dosage form such as an aerosol. The composition of the present invention is preferably a preparation to be orally administered (orally administered preparation). Further, the whitening composition of the present invention can also be in the form of a cosmetic composition such as a lotion, a cream, a lotion, a milky lotion, a foam, a foundation, a pack, a skin cleanser, a shampoo, a rinse, and a conditioner. It is.

  Formulation can be performed by a known formulation technique, and an appropriate formulation additive can be added to the formulation. Pharmaceutical additives include excipients, binders, disintegrants, lubricants, flow agents, suspending agents, emulsifiers, stabilizers, moisturizing (wetting) agents, preservatives, solvents, solubilizing agents, Preservatives, corrigents, sweeteners, pigments, flavors, propellants, and the like can be given. The formulation additives may be appropriately selected and added in an amount that does not impair the effects of the present invention.

  In the composition of the present invention, the mixing ratio of (i) tranexamic acid or a salt thereof and (ii) L-cysteine, a derivative thereof, or a salt thereof may be appropriately examined and an appropriate mixing ratio may be determined. The weight ratio is preferably (i) :( ii) = 1: 0.01 to 15, more preferably 1: 0.1 to 1.5, and particularly preferably 1: 0.32. The mixing ratio of (i) tranexamic acid or a salt thereof, (ii) L-cysteine, a derivative thereof or a salt thereof, and (iii) L-ascorbic acid, a derivative thereof or a salt thereof is appropriately examined. An appropriate blending ratio may be determined, but (i) :( ii) :( iii) = 1: 0.01 to 15: 0.01 to 60 is preferable, and 1: 0.1 to 1.5: 0. 1 to 6 are more preferred, and 1: 0.32: 0.4 is particularly preferred.

  The composition for whitening (whitening agent) of the present invention is appropriately examined depending on the sex, age, symptoms, administration (dose) method, administration (dose) frequency, administration (dose) timing of the user, and the like. You can decide the amount). For example, in the case of oral administration, tranexamic acid or a salt thereof is preferably administered (taken) in an amount of 50 to 2500 mg, more preferably 400 to 2000 mg (taken) per day. In addition, L-cysteine, a derivative thereof, or a salt thereof is preferably administered (taken) in an amount of 30 to 750 mg, more preferably 150 to 480 mg (taken) per day. L-ascorbic acid, a derivative thereof, or a salt thereof is preferably administered (taken) in an amount of 50 to 3000 mg, more preferably 300 to 2000 mg (taken) per day.

That is, in the whitening composition (whitening agent) of the present invention containing tranexamic acid or a salt thereof and L-cysteine, a derivative thereof, or a salt thereof, the blending amount is 50 to 2500 mg of tranexamic acid or a salt thereof per day, And L-cysteine, a derivative thereof, or a salt thereof is preferably administered so as to be administered (taken) in an amount of 30 to 750 mg, and 400 to 2000 mg of tranexamic acid or a salt thereof per day, and L-cysteine, a derivative thereof. Alternatively, those in which 150 to 480 mg of these salts are administered (taken) are more preferable.
In the whitening composition (whitening agent) of the present invention containing tranexamic acid or a salt thereof, L-cysteine, a derivative thereof or a salt thereof, and L-ascorbic acid, a derivative thereof or a salt thereof, the compounding amount is 1 Daily administration (take) of 50 to 2500 mg of tranexamic acid or a salt thereof, 30 to 750 mg of L-cysteine, a derivative or a salt thereof, and 50 to 3000 mg of L-ascorbic acid, a derivative or a salt thereof. Preferably, tranexamic acid or a salt thereof is 400 to 2000 mg, L-cysteine, a derivative or a salt thereof is 150 to 480 mg, and L-ascorbic acid, a derivative or a salt thereof is 300 to 2,000 mg / day. Formulated to give (administer) 2000 mg Ones are more preferable. The composition of the present invention may be prepared as a single preparation containing all the components of the present invention and administered (taken), or the components of the present invention may be divided into separate preparations, These preparations may be kit preparations which can be administered (taken) simultaneously or sequentially.

  Hereinafter, the present invention will be further described with reference to examples, but the present invention is not limited to these examples.

1. Pigmentation Inhibitory Effect 1.1 Test Method 1.1.1 Examination of Ultraviolet (UVB) Irradiation Time Ultraviolet (UVB) Irradiation Time Using Two 6-week-old Female Kwl: A-1 Brown Guinea Pigs (SPF) It was investigated. That is, one guinea pig was fixed on the abdomen, and two 2 cm × 2 cm square ultraviolet irradiation sites were provided symmetrically across the midline of the back, each of which was a total of six places. Ultraviolet (UVB) irradiation was performed from a distance of 40 cm using five SE lamps (wavelength: 250 to 350 nm, FL20SE, manufactured by Toshiba) while shielding light from the area other than the ultraviolet irradiation site. The irradiation time was 4, 6, 8, 10, 12, and 14 minutes, and the skin reaction (the presence or absence and degree of erythema) at the irradiated site was observed the next day.
Next, using another guinea pig, the irradiation time was set at an interval of 15 seconds between the minimum time when the skin reaction was observed and the maximum time when the skin reaction was not observed. After providing eight irradiation sites, the skin reaction was observed, and the ultraviolet (UVB) irradiation time in this test was determined to be two types of 11 minutes and 30 seconds and 11 minutes and 45 seconds.

1.1.2 Test sample The test sample was dissolved in water for injection to the following concentration.
Sample (1): Control (no addition)
Sample (2): tranexamic acid 37.5 mg / ml
Sample (3): L-cysteine 12 mg / ml
Sample (4): ascorbic acid 15 mg / ml
Sample (5): tranexamic acid 37.5 mg / ml + ascorbic acid 15 mg / ml
Sample (6): tranexamic acid 37.5 mg / ml + L-cysteine 12 mg / ml
Sample (7): L-cysteine 12 mg / ml + ascorbic acid 15 mg / ml
Sample (8): tranexamic acid 37.5 mg / ml + L-cysteine 12 mg / ml + ascorbic acid 15 mg / ml

1.1.3 Ultraviolet irradiation Five female Kwl: A-1 brown guinea pigs (SPF) of 7 weeks old were divided into one group and examined. That is, the guinea pig was fixed to the abdominal position using a fixing plate on the day of ultraviolet irradiation (the day of starting administration of the sample, the second and fourth days: three times of ultraviolet irradiation). One 2 cm × 2 cm square on either side of the guinea pig back midline was used as an ultraviolet irradiation site, and light was shielded from light except for the ultraviolet irradiation site. Two SE lamps (wavelength 250 to 350 nm, FL20SE, manufactured by Toshiba) were irradiated with ultraviolet light (UVB) from a distance of 40 cm for 11 min 30 sec. Was irradiated for 11 minutes and 45 seconds. The test sample was orally administered twice a day during the test period (14 days). The administration liquid volume was 10 ml / kg. In addition, on the day of ultraviolet irradiation, administration was performed after ultraviolet irradiation, and on the day of pigmentation determination, after the determination.

1.1.4 Judgment of Pigmentation Before irradiation on the start day of the test specimen administration and on the end day of the test, the irradiation site was measured for L value (brightness) using a color difference meter (CR-300, manufactured by Minolta Camera Sales Co., Ltd.). Then, the ΔL value (L value on the observation day−L value before irradiation) was determined. The results are shown in Table 1 (the larger the ΔL value, the higher the effect).

*：ｐ＜０．０５、**：ｐ＜０．０１ ｖｓ検体（１） Table 1

*: P <0.05, **: p <0.01 vs sample (1)

1.2 Results As is clear from Table 1, the samples (6) and (8) according to the present invention exhibited an excellent pigmentation-suppressing effect. That is, the tranexamic acid and L-cysteine administration groups (samples in the table) were compared with the tranexamic acid single administration group (sample (2) in the tables) and the L-cysteine single administration group (sample (3) in the table). (6)) showed an excellent pigmentation inhibitory effect.
In addition, the L-cysteine and ascorbic acid administration group (sample (7) in the table) in which the pigmentation-suppressing effect was expected to some extent did not show an unexpected effect, but rather showed an effect of promoting pigmentation. . This is clear when the results of the group administered with L-cysteine alone (sample (3) in the table) and the group administered with ascorbic acid alone (sample (4) in the table) are compared.
On the other hand, in the group to which tranexamic acid was further administered to L-cysteine and ascorbic acid (sample (8) in the table), not only the pigmentation promotion of the group to which sample (7) was administered was turned to inhibition of pigmentation but also extremely. Excellent pigmentation inhibition effect was exhibited.

2. Formulation Example 2.1 Tablets Tablets were produced according to a conventional method using the following composition (6 tablets per day).
Tranexamic acid 1500mg
L-cysteine 240mg
Crystalline cellulose 100mg
Corn starch 40mg
Low-substituted hydroxypropylcellulose 50mg
Hydroxypropyl cellulose 30mg
Magnesium stearate 20mg
Hydroxypropyl methylcellulose 2910 60mg
Macrogol 6000 12mg
Talc 10mg
18mg titanium oxide

2.2 Tablets Tablets were prepared according to a conventional method using the following composition (6 tablets per day).
Tranexamic acid 750mg
L-cysteine 240mg
L-ascorbic acid 300mg
200mg crystalline cellulose
Corn starch 100mg
Low-substituted hydroxypropylcellulose 90mg
Hydroxypropyl cellulose 30mg
25 mg of magnesium stearate
Hydroxypropyl methylcellulose 2910 80mg
Macrogol 6000 16mg
14mg talc
24mg titanium oxide

2.3 Tablets Tablets were prepared according to a conventional method using the following composition (6 tablets per day).
Tranexamic acid 750mg
L-cysteine 160mg
L-ascorbic acid 300mg
α-Tocopherol 300mg
170mg crystalline cellulose
Corn starch 200mg
Low-substituted hydroxypropylcellulose 70mg
Hydroxypropyl cellulose 30mg
Magnesium stearate 20mg
Hydroxypropyl methylcellulose 2910 60mg
Macrogol 6000 12mg
Talc 10mg
18mg titanium oxide

2.4 Tablets Tablets were prepared according to a conventional method using the following composition (6 tablets per day).
Tranexamic acid 1000mg
L-cysteine 480mg
L-ascorbic acid 600mg
Pyridoxine hydrochloride 100mg
Riboflavin 30mg
200mg crystalline cellulose
Corn starch 950mg
Hydroxypropyl cellulose 50mg
25 mg of magnesium stearate
Hydroxypropyl methylcellulose 2910 75mg
Macrogol 6000 15mg
Talc 11.5mg
Titanium oxide 22.5mg

2.5 Liquid Preparation A liquid preparation was prepared by the usual method with the following composition (100 ml per day).
Tranexamic acid 1000mg
L-cysteine 240mg
Keishibukuryogan extract 3750mg
Sorbitol 3000mg
Citric acid 100mg
Sodium citrate 30mg
Perfume appropriate amount Purified water 100ml

2.6 Tablets Tablets were produced according to a conventional method using the following composition (6 tablets per day).
Tranexamic acid 1000mg
L-cysteine 240mg
Chamomile 600mg
300mg
200mg crystalline cellulose
Corn starch 165mg
Hydroxypropyl cellulose 50mg
25 mg of magnesium stearate
Hydroxypropyl methylcellulose 2910 75mg
Macrogol 6000 15mg
Talc 11.5mg
Titanium oxide 22.5mg

2.7 Tablets Tablets were produced according to a conventional method using the following composition (6 tablets per day).
Tranexamic acid 1000mg
L-cysteine 240mg
Ceramide 20mg
150mg crystalline cellulose
Corn starch 145mg
Hydroxypropyl cellulose 25mg
Magnesium stearate 10mg
Hydroxypropyl methylcellulose 2910 42mg
Macrogol 6000 7mg
Talc 168mg
7mg titanium oxide
660mg white sugar
Gum arabic 17mg
Precipitated calcium carbonate 150mg

2.8 Tablets Tablets were produced according to a conventional method using the following composition (6 tablets per day).
Tranexamic acid 1000mg
L-cysteine 480mg
Flavangenol 30mg
Collagen 1000mg
Crystalline cellulose 203mg
Low-substituted hydroxypropylcellulose 70mg
Hydroxypropyl cellulose 50mg
Magnesium stearate 27mg
Hydroxypropyl methylcellulose 2910 80mg
Macrogol 6000 16mg
14mg talc
24mg titanium oxide

2.9 Burnishing cream A vanishing cream (100 g) was produced with the following composition by a conventional method.
(A) 1.0 g of polysorbate 60
0.5 g of POE (60) sorbite tetraoleate
Glyceryl monostearate (self-emulsifying type) 1.0 g
Cetyl palmitate 4.0 g
Paraffin wax (135 ° F) 3.0g
8.0 g of stearic acid
Behenyl alcohol 2.0g
Cetyl isooctanoate 6.0 g
Butyl paraben 0.1 g
(B) Methyl paraben 0.1 g
2% aqueous sodium hydroxide 4.0 g
1,3-butylene glycol 7.0 g
Tranexamic acid 1.0g
L-cysteine 1.0g
Purified water residue

2.10 Emulsion An emulsion (100 g) was prepared according to a conventional method with the following composition.
(A) 1.0 g of polysorbate 60
0.5 g of POE (60) sorbite tetraoleate
Glyceryl monostearate (lipophilic type) 1.0 g
Stearic acid 0.5g
Behenyl alcohol 0.5g
Liquid paraffin 4.0g
Glyceryl tri-2-ethylhexanoate 4.0 g
2.0 g of cetyl isooctanoate
Butyl paraben 0.1 g
(B) Methyl paraben 0.1 g
Carboxyvinyl polymer (1% aqueous solution) 5.0 g
1,3-butylene glycol 5.0 g
Tranexamic acid 1.0g
L-cysteine 1.0g
1.0 g of L-ascorbyl magnesium phosphate
90.0 g with purified water
(C) 1% aqueous sodium hydroxide solution 2.5 g
7.5 g of purified water
(D) Suitable amount of fragrance

2.11 Lotion agent A lotion agent (100 g) was produced according to a conventional method with the following composition.
(A) POE (60) hardened castor oil 1.0 g
Perfume appropriate amount ethanol 15.0g
Methyl paraben 0.1 g
(B) Citric acid 0.1 g
0.3 g of sodium citrate
1,3-butylene glycol 4.0 g
Tranexamic acid 1.0g
L-cysteine 1.0g
1.0 g of L-ascorbyl magnesium phosphate
Purified water residue

Claims (15)

  A composition containing (i) tranexamic acid or a salt thereof, and (ii) L-cysteine, a derivative thereof, or a salt thereof.   A composition containing (i) 50 to 2500 mg of tranexamic acid or a salt thereof, and (ii) 30 to 750 mg of L-cysteine, a derivative or a salt thereof, as a daily administration (dose) amount.   A composition comprising tranexamic acid and L-cysteine.   A composition containing 50 to 2500 mg of tranexamic acid and 30 to 750 mg of L-cysteine as daily administration (dose) amounts.   A composition comprising (i) tranexamic acid or a salt thereof, (ii) L-cysteine, a derivative or a salt thereof, and (iii) L-ascorbic acid, a derivative or a salt thereof.   (I) tranexamic acid or a salt thereof in 50 to 2500 mg, (ii) L-cysteine, a derivative thereof or a salt thereof in 30 to 750 mg, and (iii) L-ascorbic acid in a daily dose (dose) amount; A composition containing 50 to 3000 mg of the derivative or a salt thereof.   A composition comprising tranexamic acid, L-cysteine and L-ascorbic acid.   A composition containing 50 to 2500 mg of tranexamic acid, 30 to 750 mg of L-cysteine, and 50 to 3000 mg of L-ascorbic acid as daily doses (dose).   The composition according to any one of claims 1 to 8, which is for whitening.   The composition according to any one of claims 1 to 8, which is used for prevention and / or treatment of pigmentation.   The composition according to any one of claims 1 to 10, wherein the dosage form is a formulation for oral administration.   A whitening method comprising administering (i) tranexamic acid or a salt thereof, and (ii) L-cysteine, a derivative thereof, or a salt thereof.   A whitening method comprising administering (i) tranexamic acid or a salt thereof, (ii) L-cysteine, a derivative or a salt thereof, and (iii) L-ascorbic acid, a derivative or a salt thereof.   A method for treating pigmentation, which comprises administering (i) tranexamic acid or a salt thereof, and (ii) L-cysteine, a derivative thereof, or a salt thereof. (I) administering tranexamic acid or a salt thereof, (ii) L-cysteine, a derivative or a salt thereof, and (iii) administering L-ascorbic acid, a derivative or a salt thereof, Treatment method.