Note: Descriptions are shown in the official language in which they were submitted.
CA 02431745 2003-06-11
1
DESCRIPTION
EXTERNAL PREPARATION FOR TREATING DERM.?~TOSIS AND PRURITUS
DUE TO HE1'~IODIALYSIS
BACKGROUND OF THE INVENTION
FIELD OF THE TNVENTION
The present invention relates t~~ therapeutic agents
for xerosis cutis (skin-dry) dermatos~.s such as exanthema,
or pruritus which becomes problem to patients receiving
hemodialysis treatment.
In more detail the present irmention relates to
external preparations for treating dermatosis and/or
pruritus due to hemodialyss.s, which contains
acetylsalicylic acid as an active ingr_edient~ and a. method
for treating said diseases by administering transdermally
said external preparations ir. ar~ amount of an effective
dose to patients sufferi:n~ from said diseasesa
DESCRIPTION OF THE RELATED ART
Recently, with increase of patients suffering from
endocrinism such as diabetes, and dysmetabolism such as
nephropathy, patients who receive hemodialysis treatment
are increasing. In the patients receiving hemodialysis
treatment, turning for the deterioration of the skin
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condition and strong itching on body have become severe
problem.
In regard to itching or pain on the patient receiving
hemodialysis treatment, many studies have been doize, but
the mechanism thereof has not dissolved anct that said
patients are hardly cured comparing with the patients
receiving no hemodialysis treatment. In addition there is
none of agents effective to ~ruritus dL:ring hemodialysis
treatment.
1C
Nowadays many antipruritic agents for oral
administration such as anti~~istamines etc. are sold. In
case of such an agent being takenp it is anxious for its
side effects, such as sleepiness, worthlessness feeling,
etc. It is more difficult to use an antipruritic agent for
oral administration to tre patier~~ receiving hemodialysis
treatment, because frequencies of the side effects to the
patients are higher comparing ~.~aith ones to healthy persons.
On the other hand, an activity to dermatosis and an
antipruritic activity of an external preparation containing
an antihistamine or a nonsteroidal ant_inflammatory agent
are not satisfactory. Especia l=y the preparation
containing an antihistamine is also anxious for its side
effects such as dermal anaphylaxis, and the preparation
containing a nonsteroidal ar~tiinfl_ammatory agent is also
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anxious for its side effects, such as dermal irritation,
contact dermatitis, etc.
Furthermore, although steroids for an external
application are very useful for treatment of eczema, skin
pruritus, etc., these steroids are not cnly anxious for
their side effects, such as atrophia cubs, steroid flush,
angiotelectasis, etc., when repeatedly taken, but also
these steroids are transo:ermally absorbed to migrate to
blood and have a possibility to gizre :>ystE:mically bad
effects.
Acetylsalicylic acid (Hereinafter it may be wr~_tten as
Aspirin. ) has a strong analgesic actl_-Ui.ty, an ant~~febrile
activity and an antirheuma-tic activity being less in its
side effects and being su~cerior in. its safetyo Therefore,
acetylsalicylic acid has been w7dely used from of old.
Recently studies for new uses of external preparations
containing acetylsalicylic acid have been done. For
example, ointments for treating neuralgia (Japanese Patent
Pub. A3-72426), external preparations for treating skin
injury (Japanese Patent Pub,. A9-235232), a transdermal
administration system for treatment of thrombosis and for
prophylactic treatment of cancer (Japanese Patent Pub.
Tokuhyo 8-50198) are illustrated.
However, any external preparation containing
acetylsalicylic acid for treating deterioration of skin
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condition and pruritus on body for_ tr_e patieni~s receiving
hemodialysis treatment, and therapeutic effects thereof
have not been reported.
SUMMARY OF THE II~IVENTIOhT
An object of the present invention is to provide
external preparations v,Thich have an activity for
improvement of skin condition and an excellent antipruritic
activity on the patients receiving hemodialysis treatment
and are less in their side effects.
The present invention relates to external preparations
for treating dermatosis and/or pruritus due to hemodialysis,
which contains acetylsalicylic acid as an active ingredient
and a method for treating said diseases by a.dminrsterir~g
transdermally said exterv~al preparations in an amount of an
effective dose to patients suffering from said diseases.
Further scope of app=~_icability of the present
invention will become apparent from the detailed
description given hereinafter. However, it should be
understood that the detailed description and specific
examples, while indicating preferred embodiments of the
invention, are given by way of illustration only, since
various changes and modifications within the spirit and
scope of the invention wil_L become apparent to those
skilled in the art from this detailed description.
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BRIEF DESCRIPTION OF TEE DRA~~1INGS
Fig. 1 is a photo of a knee of a patient receiving
hemodialysis treatment before administration of the
external preparation of -the present invention.
5 Fig. 2 is a photo of 'the same lesion of the patient
after administration of the external preparation of 'the
present invention.
DETAILED DESCRIPTION
The present inventors have earnestly studied and as a
result, have found that peahen an external preparation
containing acetylsalicylic acid as an active ingredient is
administered to a patient receiving hemodialysis treatment,
the preparation is less in its side effects and shaves an
excellent antipruritic activity and an excellent activity
to dermatosis. Thus t;he present invention has been
completed.
Namely, the present inventors have prepared the
external preparation containing acetylsalicylic acid and
~.lhen the preparation has been applied to, for e~:ample a
lesion with itching and dermat~osis, such as injured skin,
eczema, tuber, ulticaria, prutitus, bulla, edema, et c., the
excellent therapeutic activities thereto have been found.
Acetylsalicylic acid contained ir~ the external
preparation of the present invention is described in the
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Pharmacopoeia of Japan XIII and USP 26.
The dosage of Aspirin transdermally administered to a
patient depends on the condition of the patient, but it is
usually 0.01-200mg/day/body weight (60kg}.
The external preparation of the present invention is
applied to in the usual manner, such as, applied directly
to the affected legion or is once painted or immersed an
the cloth and then applied to the affected legion.
The diseases which the external preparation of the
i0 present invention is applied to are xerosis cutis, with
itching and dermatosis, such as injured skin, eczema, rubor,
ulticaria, pruritus, bulla, edema, etc. in patients
receiving hemodialysis treatment.
The amount of acetylsalicylic acid contained in the
external preparation of the present invention depends on
form of the preparation but .is 005-800~~ preferably 0.05-
700, more preferably 0.1-50o per total amount by weight.
When the amount of acetylsalicylic acid is more than 80o by
weight, it is impossible to maintain the physical property
as an external preparation. Wizen the amount of
acetylsalicylic acid is less than Or05o by weight, the
antipruritic activity by acetylsalicylic acid does not show
enough. The amount as more than 80o cr less than 0.050 by
weight, therefore is not preferable.
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The external preparation of the present _invention is
not limit ed as far as ~t is the p.r_eparation in which
acetylsalicylic acid can. be directly applied on the local
surface of skin, such. as ointments, solutions (e. g.
suspensions, emulsions, lotions), cataplasm;~, patches,
plasters, tapes, aerosols and external. powders (powders for
external use).
As other ingredients except acety?_salicylic acid of
the external preparation of the present lnver~tion can be
used any ;ingredient used a_n the ordinarily external
preparations.
In case of ointments, creams, gels and lotions, bases,
such as white vaseline (petrolatum), yellow vaseline,
lanolin, purified bee wax, cetanol, stearyl alcohol,
stearic acid, hydrogenated oil, hydrocarbon gel,
polyethylene glyco-~, liquid par_af_fin a:rld squalanea solvents
or solubilizing agents, such as o~_elc acid, isopropyl
myristate, glycerol tri.isooctanoate, crot amii~ons diethyl
sebacate, diisopra-,oyl sebacate, diiso,propyl ac'~ipate, hexyl
laulate, a fatty acid., a fatty acid ester, an aliphatic
alcohol, and a plant oil; antioxidants, such as a
tocopherol derivative' L-ascorbic acid,
dibutylhydroxytoluene and butylhydroxyanisoleo antiseptics
such as p-hydroxybenzoate; humectants, such as glycerin,
propylene glycol and sodium hyaluronatea surfactants, such
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as a polyoxyethylene derivative, a glycerol fati~y acid
ester, a sucrose fatty acid ester, a sorbitar~ fatty acid
ester, a propylene glycol fatty acid ester and lecithin;
thickening agents, such as carboxyvinyl polymer, xanthan
gum, carboxymethyl cellulose, sodium carboxymeth_yl
cellulose, hydroxypropyl cellulose and hydroxypropylmethyl
cellulose; stabilize_rs9 preserva.-t~_vesa absorption
enhancerso and other suitable fillers niay be added.
In case of tapes, tacking agents, such as a stylene
isoprene-stylene block copolymer and. an acrylate resinP
tackifier resins, such as an alicyclic saturated
hydrocarbon resin, a hydrogenated rosin. resin a.nd a. terpene
resins softeners, such as liquid gum anal liquid paraffin
antioxidants such as dibutylhydroxytolueneo polyhydric
alcohols such as polyethylene glycol; absorption enhancers
such as oleic acids surfactants such as a pol_yoxyethylene
derivatives and other suitable fillers may be added. In
addition a water-absorbable polymer, sur_h as sodium
polyacrylate and polyvinyl alcohol, and a small amount of
purified water may be added to prepare tape preparations
containing water.
In case of aerosols; bases, such as white vaseline
(petrolatum!, yellow vaseline, lanolin, purified bee wax,
cetanol, stearyl alcohol, stearic acid, hydrogenated oil,
hydrocarbon gel, polyethylene glycol, liquid paraffin and
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squalane; solvents or solubilizing agents, such as oleic
acid, isopropyl myristate, isopropyl adipate, diisopropyl
sebacate, glycerol triisooctanoate, crotamiton, diethyl
sebacate, hexyl laurate, a fatty acid, a fatty acid ester,
an aliphatic alcohol and a plant oil; antioxidants, such as
a tocopherol derivative, L-ascorbic acid,
dibutylhydroxytoluene and butVlhydrox_yanisolee antiseptics
such as p-hydroxybenzoate; humectants, such as glycerin,
propylene glycol and sodium hyaluronate; surfactart:s, such
as a polyoxyethylene derivative, a glycerol tatty acid
ester, a sucrose fatty acid ester, a sorbitan fatty acid
ester, a propylene glycol_ fatty acid ester and lecithin;
thickening agents, such as carboxyvinyl polymer, xanthan
gum, carboxymethyl cellulose,, sodium c:arboxymethyl
cellulose, hydroxyp.ropyl cellulose and hydrox~rpropylmethyl
cellulose, as used in the ointments, the creanus, the gels,
the suspensions, the emulsifying agents or the lotions;
stabilizers; buffering agents; sweetening agents;
suspending agents; emulsifying agents,P flavors;
preservatives; solubili.zing agents; and other suitable
fillers, may be added.
In case of external powders, fillers, sL.ch as potato
starch, rice starch, corn starch, talc and zinc oxide, and
other suitable additi~re;~ may be added.
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The external preparation of the present i:nvent.ion can
be prepared, for example by well kneading each ingredient,
if necessary with a suitable base, in accordance with a
usual manner.
5 In case of preparing ointments, using fat, fatty oil,
lanolin, wax, resin, plastic, glyccls, highe r molecular
weight alcohols, glycerin, water, emulsifier, suspending
agent, or other suitable ingredients as a starting material,
or these ingredients as a base and adding a medicament
10 thereto the resulting mixture are kneaded to become
homogeneity. Namely, tre ingredients for the base are
dissolved under heating and mixed to beccme homogeneity and
if necessary, absorption enhancer, antioxidant,
preservative, purified waver, etc., is added Teen
25 acetylsalicylic acid in powders is added under stirring and
kneaded to prepare ointments or creams.
For example, in case of preparing oleaginous ointments,
a base is melted under warming and mixed and after the
mixture is semi-cooled, a medicament ir= powde r or solution
is mixed with a part of the base. Then the mixture is
mixed with the rest of the base to become homogeneity.
For example, in case of preparing emulsified or water-
soluble ointments, after the solid base is melted on a
water bath and to the melted base keeping at about: 75°C is
added the water-soluble base which is d.isso7_ved in water
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kept at the same temperature or a little higher. The
mixture is kneaded to become homogeneity. In case of
adding another medicament to this mixture, according t0 the
property of the base, a water-soluble or oil-soluble
medicament is first mixed with a part of the base and then
homogeneously with the rest of the base.
In case of preparing tapes, to a tacking agent such as
an acrylate resin or a stylene-isoprene-stylene block
copolymer are added tacl~ifier resins, such as an alicyclic
saturated hydrocarbon resin, a hydrogenated rosin resin and
a terpene resin, softeners, such as -Liquid gum and liquid
paraffin, absorption. enhancers and antioxidants. The
mixture is dissolved i.n an organic solvent such as toluene,
or is melted under heating and the zraixtur a is well mixed.
To the mixture is mixed a medicament in powder or in
solution. The m~zxture is spread on a release paper. In
case of a soluble type, after spreading and dry, the paper
is laminated on a flexible support such as with
polyurethane film, polyethylene fil_ma poly chlorinated
vinyl film, woven cloth or unwoven cloth and then cut in a
desired size.
In case of preparing lotions, a medicament, a solvent,
an emulsifier, a suspending agent, etc., are added to an
aqueous solution and the mixture is homogenized. In case
of preparing suspending lotions, after pulverizing -the
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medicament and making it wettab 1e with. glyceri.:n or ethanol
etc., then thereto is gradually added a solution of a
suspending agent or a base of the lotion and the mixture is
homogenized. In case of preparing emulsifying lotions, an
oil-soluble medicament and an oil layer are put in one
vessel, and an aquecus layer -_s put i:n other vessels Each
vessel is warmed, and in case of preparing 0/T~7 type
emulsion, the oil layer is gradually added to the aqueous
layer, and in case of preparing W%O type emulsion, in
contrast, the aqueous layer is gradually added to the oil
layer. mach mixture ccntirlues to be mixed until the
emulsifying is completed.
In case of preparing the aerosols, an ointment, a
cream, a gel, a suspension, an emulsion, a solution or a
lotion, etc. is p-~epared lay the method as mentioned above
and then, it is poured with a liquid gas or a compressed
gas in a sealed vessel to prepare the aerosols.
The diseases which the external preparation of the
present invention is applied to are, as mera fined above,
xerosis cutis, with itching and dermatosis, such as injured
skin, eczema, rubor, ulticaria, pruritus, bulla~ edema, etc.
in patients receiving hemodialysis treatment.
MODE FOR CARRYING OUT THE INVENTION
The external preparations containing acetylsalicylic
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acid of the present invention are explained by examples and
experimental examples, but the present invention is not
limited by these examples.
Examples 1-6 ~j0intmentsl
According to ingredients indicated in Table 1, an
ointment base (vaseline or 'hydrocarbon gel), a solvent
(Tween 80, crotamiton, an a_lcohcl, diisopropyl ads_pate or
isopropyl myristate} anal Aspirin were dissolved or
dispersed under well stirring on a water bath. Then the
mixture was cooled under stirring to prepare ointments.
Table 1: Ingredients of ointments containing Aspirin
Examples ~ .1 ~ 2~~ ~ - ~ 5 6
4 -'- _,_
ingredients ~ Ingredie:~~t I
ratio(wt
o
}
Aspirin ' 0.1 1.0 10.01 0.5 5.0 2.0
Ethanol ~ 1.0 2.0 10.0 - - -
8 G.- ~~ - - - ; - _
Tween - 5
0
Crotamiton j - - _ - 5.0
Diisopropyl adipate - - - - - 5.0
Vaseline , 98.9 - 80.0 94.5 - -
~
Hydrocarbon gel - 97.0- 90.0 97.0
Examples 7-9 (Lotion s
According to ingredients indicated in Table 2, Aspirin
was added to a warmed oil.. layer to be dissolved or
dispersed. Separately otter ingredients were dissolved in
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previously ~,aarmed purified . ~.aai~er ~ and the oil layer was
added thereto under vigorously stirring. The mixture was
mixed to homogeneity under gradually cooling to prepare
lotions.
Table 2o Ingredients of lotions containing Aspirin
E x amp l a s ~' 7 ~~_ 8 ~~
g
Ingredients ~ Ing ent
ratio
(wto)
Aspirin ~ 0.05 0.5 5.0
Crotamiton ~ 1.0 2.0 5.0
Isopropanol - -~ 2.0
Diisopropyl sebac~~.te 1.0 - -
E~
Squalane 3.0 3.0 3.0
~ 3v0 3.0 3.0
Cetanol
-- 0.5 0.5 0.5
Solbitan sesquioleate
Polyoxy(20)cetyl ether 1a5 1.5 1.5
Propylene glycol 5.0 ~ 5.0 5.0
Triethanolamine 0.4 ' 0.4 Oa4
Purified water ( 84.55 ?7.0 74,.~
L
Examples 10-12 (Ge,~. s~
According to ingredients indicated in Table 3~ after a
water soluble polymer was melted on a relater bath Pspirin
wa.s dissolved or dispersed in a solvent(s:) and these
ingredients with other bases were homogeneously mixed to
prepare gels.
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Table 3: Ingredienv~.s of gels containing Aspirz_n
Examples ~~ 10 C 11~ 12
Ingredients Tr~.gredieni= ratio ('at
o;
Aspirin Om2 2~0 20.0
Crotamiton ~ 1.0 5~0 2.0
Isopropanol i~ 1.0 ~ - 2.0
~
Propylene glycol ~5m0 '1 5x0 36.0
Polyacrylic acid ~ 25m0 2 50 25.0
Triethanolamine ~ 0.7 0.7 0.7
Purif i ed wa ~~ ~'.7 . 1 2 . 3 ~ l4
ter_~ ~-- 2 0 3
Examples 13-15 (Creams)
According to ingredients indicated in Table 4, after a
solid base was melted on a water bath Aspirin dissolved or~
dispersed in a solvent U~as added thereto. A water--soluble
base was dissolved in ara.ter and its warmed ;sol,ation Haas
added to the mixturem The mixture was }cneaded until it
became homogenous to prepare creams.
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Table 4: Ingredients of ointments containing Aspirin
Examples ' 1~ 14 15
Ingredients Ingredient (wto)
ratio
Aspirin 4.0 4.0 4.0
~ Crotamiton 1. 0 1. 0 1_
.
0
Sesame oil 2.0 - 1.0
a i
~Diisopropyl sebacate ~ 2.0 1.0
i
Cetanol 9.0 9~0 9.0
l
White vaseline 8.0 8.0 8.0
F
1
Hexyldecanoi 1.0 1D0 1.0
Polyethylene glycol monostea_rate 2.0 2.0
I
2.0
Polyoxy(9)lauryl_ ether 2.8 E 2.8 ~ 2.8
!Polyoxy(23)cetyl ether 2,00 2.0 2.0
Propylene glycol 12.0 I2.0 i2.~
~
Methylparaben 0.1 I 0.1 0.1
i
~Propylparaben 0.1 0.1 0.1
iPurified water 4 0 54.0 54.0
Examples 16-18 (1'a~es)
According to ingredients indicated in Table 5~ to a
tacking agent consisting of an acrylate resin or a stylene-
isoprene-stylene block copolymer were added <~n alicyclic
saturated hydrocarbon resinY liquid paraffiny polybutene9
an antioxidant, etc. and the mixture was dissolved in an
organic solvent such as toluene etc. ura.der stirring,, or the
mixture was melted by heating under stirring. Thereto was
added Aspirin and the resulting mixture was spread on
release paper and then in case of a soluble type~ was
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spread on release paper and dwried. T:iZe relea:~e paper was
laminated on a flexible support to be cut into a desired
size to prepare tapes.
Table 5o Ingredients of tapes coru~aining ~sspirin
Examples l~ 17~~ 1
Ir~gredier.ts Ingredient ratio (wt o )
Aspi rin - 5. 0 7_0 0. 0 ~ 30 . 0
Isopropyl myristate ~ 5.0 - ~ -
'Diisopropyl adipate - - 5.0
!
~Crotamiton 500 5a.0 ; 1 0 !
Acrylate-vinyl acetate copolymer - 85..0 -
Stylene-isoprene-stylene E'-
20.0 - i! 13.4
block copolymer _- ~ __;
Alicyclic saturated 4200 - 23.5
hydrocarbon resin _~ t
Polybutene _- 15.0 - ~~ 11.6
~ Liquid paraffin ~ ;1.0 - ~) 14~5~
Dibutyl hydroxytoluene 1.0 - ~I 1.0
iL_-
Examples 7_9-21 (PowdersZ
According to ingredients indicated in Tab_Le 6~ potato
starch~ zinc oxide anal Aspirin were well mixed to prepare
powders.
Table 6e Ingredients of powders containing Aspirin
E mplas-
Ingredients Ingredient ratio (wt'o )
Aspirin 20.0 40.0 80.0
..
Potato starch 76.0 56.0 16.0
Zinc oxide 4.0 4.0 4.0 !
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Comparative examples 1-3
According to the method of preparing ointments,
ointments having an ingredients} of Table 7 (comparative
examples 1-3) were prepa.redo
Table 7 o Ingredients of oirltrrients (Cornparat~_VE~ examples
Comparative examples ~~~C- 2~C 3
Ingredients Ingredient ratio (wt a )
Diphenhydramine 1~0
Dexamethasone 0.1
Propylene glycol ~ ._0 0 0 10 ~ 0
Isopropyl myr=estate j 5e0 5v0
Hydrocarbon gel ~8~e0 84.9 C100.0~
Clinical Testsa
An antipruritic activity was tesf~ed dy administering
the external preparations of the present invention and
control-preparations to patients receiving hemodialysis
(volunteers)a
The degree of improvre_nenL of skin condition or itching
was evaluated based on tze following five steps stand.arda
A: Remarkably effective,
Bm Effective,
C~ Slightly effective,
Da No change,
Ee Worse.
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Being slightly effective (C) or more than slightly
effective (A, B), degree was judged too be effective, and
its effective rate was calcula-~ed.
Experiment l: Improvement of s:'~in conditvons
The external preparation of the present invention
containing Aspirin was administered to affected lesions of
patients having dermatosis (bad skin conditions) and
skin itching among patients receiving hemodialysis
10 treatment. Degree of improvement of the skin conditions
was evaluated.
As controls, the preparations of comparative examples
1 to 3 were ad.minist.ered to the '7 patients raving
dermatosis and skin itching in the same manner as above.
The result was shown in Table 8.
Table 8o Degree of impvyovement of skin conditions due to
hemodialvsis
Drugs ~I~lo. of E~Talu~~tion yffective
Group i_ o ~ o
(w~ o ) patient A B ~ C D ~ E race ( ~ )
Example 2 Aspirin ( 1. 0 ) 2 1 0 1 0 ~ 0 100 . 0
Example 4 Aspirin (0.5) 3 2 1 0 0~0 100.0
Example 6 Aspirin (2.0) ~ 3 0 0 0~0 100.0
Example 13 Aspiri n ( 4 . 0 ) v2~ 0 1 0 l i 0 ~ 50 . 0
Comp . Diphen- ~ 3 0 0 0 3 ~ 0 0
Ex.1 hydramine(1.0)
Comp. Dexamethasone
3 0 0 1 2 0 33.0
Ex.2 (0.1 )
Comp . _ _-~ -~ 0 0 ' 0 0 1 0
E x . 3 ~ ~ ~ ~-_
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As is clear from the result in Cable 8~ preparations
of examples 2~ 4~ 6 and i3 containing A.spirir~ (the
preparations of the present in~entio:r~) showed improvement
of the skin condition due to hemodialysis and the effects
5 were strong comparing with. controls (preparations cf
comparative examples 1 to 3)a
Experiment 2a Improvement of itc'_~ing
The external preparation containing Aspirin was
10 administered to affected lesions of 12 patients having
itching among patients receiving hemod_ialysis treatmentm
Degree of improvement of the itching was evaluatedo
As controls, the preparations of comparative example 1
to 3 were administered to the 7 patients having itching in
15 the same manner as above
The result was shown in Table 9e
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Table 9: Degree of improvement of itching due to
hPm~c~ialvSiS
Evaluation n
Drags I No. of affective
Groins (wt o) ~ patient A g C D E rate ( )
r
-
~
Example 2 Aspi rin ( 1. ~2 1 1 0 0 100 . 0
0 ) ~ I
0
Example 4 Aspirin (0.5) 3 2 1 0 0 ~0 100.0
r
Example 6 Aspirin (2.0) ~ 3 2 0 1 0 ; 100.0
~ 0
Example 13Aspirin ( 4 s 2 1 1 0 0 ' 100 . 0
. 0 ) 0
E~ xample17Aspirin ( 1 _2 0 1 1 0 0 1000
0 . 0 )
Comp. Diphen- (~ -
3 0 0 2 1 I 0
0
Ex . 1 hydramine (
I 1. 0 )
Comp. Dexamethasone 3 0 0 1 2 ~ 33.0
0
Ex.2 (0.1) -~
-- ~1 0 (0 0 0 ~1 0
As is clear from tze result in 'fable 9, preparations
of examples 2, 4, 6, 1.3 arid 17 containing Aspirin (the
preparations of the :~resent invention) inhibited the
itching due to hemod:iall~sis ar:d showed very strong
antipruritic activity, comparing with controls (the
preparations of corrparat_we examples 1 to 3).
POSSIEILITY OF INDUSTRIAL APPLICABILIT'~
The external prepara.tiorl of the present invention
containing Aspirin as an active ingredient has an excellent
therapeutic effect to itching due to hemod_alysis.
furthermore, the external preparation of the present
invention shows im~rovem.ent for skin conditions as well as
sedative for itch-ng. The external_ preparation of the
present invention does not affect any value of clinical
CA 02431745 2003-06-11
22
assay (pathology) and belongs to the drug ~>howi-ng very
little side effects and therefore, is cons__dered as a
safety medicamentm The present inven~~ion can provide -the
external preparation being nov only excellently effective
to various itching due to hemodialysis, but also shows
improvement for skin conditions and being ver_~y little in
its side effects.
