Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
~ ~ 6 0 ~ 5 1 pcTnB95loo282
w095/22346
USE OF CERULETIDE DIETHYL AMINE SALT IN THE
TREATMENT OF PSORIASIS
The purpose of the present invention is the
use of ceruletide diethyl amine salt (Takus) for
the treatment of psoriasis.
The treatment of this skin affection has been
heretofore effected by using etretinate (Tigason)
which, however, slightly influences the damages
that psoriasis may cause on skin keratisation.
1~ Moreover, said substance can develop tolerance and
teratogenic effects, especially during a chronic
treatment.
Ceruletide, a well known decapeptide first
extracted from the skin of Hyla caerulea, the
Australian frog, and then prepared by synthesis,
has the following formula:
Pyr-Gln-Asp-Tyr-Thr-Gly-Trp-Met-Asp-PheNH2
SO3H
the diethyl amine salt thereof beinq commercially
named "Takus".
Therapeutically, it is used as a diagnostic
a~ent in the investigation of the functional state
of the gall bladder and pancreas, besides to being
used as a stimulant of the gastric secretion.
wos5/22346 PCT~B95100282
21 602S1 2
It has been surprisingly found that ceruletide
diethyl amine salt can be used, with very good
results, for the treatment of psoriasis.
The effectiveness of said substance in the
treatment of different forms of psoriasis:
psoriasis guttata, psoriasis figurata, psoriasis
nummularis, psoriasis geografica and psoriasis
seborrhoica has been ascertained in 12 volunteers
(9 men and 3 women). The substance has been used
alone in order to avoid synergistic pharmacological
effects with other kinds of drugs, thus making
possible to evaluate the positive effects per se on
the skin affection.
The use of ceruletide diethyl amine salt,
administered by a single intramuscular injection in
the dose from 2.5-5.0 ~q, led to a significant
improvement of the affection in all of the
patients, with no exception, such an improvement
lasting for 1-3 months.
The sleep improvement, the stabilisation of
the moral state and the decrease of the itch were
noted in the first days next to the application.
The disappearing of scales and a siqnificant
reduction of the badqes, which became soft and pale
W095/22346 ~ ~ 6 Q 2 ~ ~ PCTAB95/00282
and finally disappeared, were noted within 1-2
weeks.
Only one injection of ceruletide diethyl amine
- salt is normally sufficient for the treatment of
psoriasis quttata.
A second injection of the formulation
administered as well in doses of 2.5-5.0 ~q is
needed, payinq attention to the individual
sensibility of the patient toward ceruletide
diethyl amine salt, in the presence of particularly
resistant badges.
The skin of the badqes acquired a normal
colour durinq the treatment with ceruletide diethyl
amine salt whereas, usin~ an ointment of the
commonly used type (for example mercury ointment),
as an alternative, depiqmentation was always noted.
In the case of psoriasis concomitant with
alcoholism, there was a full normalisation of the
skin disorder after a sinqle use of ceruletide
diethyl amine salt, the positive effects of which
lasted for about 5-6 months. After startinq a~ain
with alcoholism, a relapse of psoriasis in the
first 1-2 months from the renewed intake of alcohol
was noted.
Examples:
W095/22346 2 1 6 0 2 3 1 PCT~B95/00282
EXAMPLE 1: Patient A.V., man, 20 years old,
single, cook
Diagnosis: psoriasis nummularis, alcoholism.
Anamnesis: the first symptoms of psoriasis
appeared after a car accident that happened when he
was 15 years old.
2-3 months later the patient noted stains on
his elbows and then the badges spread on his arms,
legs, chest and shoulders.
lo Exacerbation occurred especially during the
winter months. The patient, when he was 17 years
old, having the complicated inheritance of his
father, became a chronic alcoholic: in the meantime
he noted an aggravation of his condition too.
Repeated treatments with tar ointments,
cortisone liniments, vitamins and sedative drugs
did not lead to any improvement: the badges could
even disappear and then reappear in different
places such as elbows and knees.
The patient, when examined, complained itch
and the presence of badges on his elbows, arms,
legs, shoulders, forehead and around his ears.
The badges on his forehead measured 2.5x3 and
5.0x4.0 cm2i on the internal surface of his left
1bow 6.0xS.0 cm2i 3.0x2.5 cm2 3.0x2.0 cm2; and a
~ pcT~Bs~loo282
W09sl22346 ~ ~v ~
form of psoriasis guttata (23 badges) was present
on his right elbow: 8.0x5.5 cm2, 8.0x2.5 cm2, 3x2.5
cm2 together with other 28 smaller badges.
There were badges of psoriasis guttata and
other badges as large as a coin on the whole back.
25 badges of psoriasis guttata and nummularis were
on the lateral part of his left thigh. 32 purple
badges, measuring 4.5x5.5 cm2 at most, mostly
covered with scales, were on the internal part of
the thigh. 28 badges measuring from 0.5x0.5 cm2 to
1.8x2.0 cm2 were on his right thigh.
A badge having a diameter of 5.0x6.0 cm2 was
noted on his front-upper left shin-bone, while the
same zone of his right shin-bone was covered with
28 purple badges.
Treatment with ceruletide ~iet~yl A~i ne salt
The patient was treated with a single
injection of 4.9 ~g of ceruletide diethyl amine
salt.
The day after the treatment, the patient A.V.
noted a sleep improvement and decrease of the itch.
Two weeks later, the badges became soft and pale:
the ones on the back turned into a ring.
woss/22346 PCT~Bs5/00282
~ 16~25~ ` 6
Spaces, among the badges which were present on
his forehead, elbows and legs appeared after one
month.
The badges on the back went pale and
semicircular, the ones on his legs reduced. The
improvements of the skin disorder lasted for 3
months of the observation, when all of the badges
disAppeAred: the positive effects being noticeable
even after ten months.
Then the patient started to drink alcohol
again, from time to time, till, after the last
drink, a relapse of psoriasis occurred, which was
customarily treated in a specialised clinic with
vitA~ins, quartz lamps and liniment for 41 days.
3 days after the discharge from the clinic the
patient started to drink alcohol again and during
the next week all of the symptoms of the disease
reAppe~red. Comparing the two treatments effected,
the one with ceruletide diethyl amine salt
protracted his beneficial effects for a longer
time.
EXAMPLE 2: Patient N.I., woman, 35 years old,
chronic gastritis
Diagnosis: psoriasis figurata and guttata,
ch~onic gastritis.
~1~0~
W095/22346 PCTAB95/00282
Anamnesis: the first symptoms of psoriasis
appeared after 2 months from an accident. The
patient suffered from insomnia, amenorrhea and
irritability.
Some months after the accident some stains
~ppe~red on the contused part, and there were some
stains on her chest and on her back. She was
treated by vitamins, sedative drugs and tar
ointment.
lo The stains dic~rre~red on the back and on the
chest but reappeared on her face, arms and legs.
The skin was depigmented in the places of the
treated stains.
The patient complains itch after bathing and
badges on the knees, feet, abdomen and arms.
Dimensions of the badges: one badge measuring
5.5x6.0 cm2 on her left leg and two badges
measuring 6.5x4.5 cm2 and 2.0x3.5 cm2 on her right
knee; guttata forms of the badges were noted on her
chest, back and on the medial part of her arms.
Treatment with ceruletide ~iet~yl amine salt
The patient was treated with a single
injection of 4.5 ~g of ceruletide diethyl amine
salt.
W095/22346 ~ 16 ~ pcTnBssloo282
The patient noted the disappearing of
irritability, itch and peeling of the badges the
day after the treatment with an injection with
ceruletide.
The badges on her back and chest became pale
and short spaces appeared among them after one
week.
The depigmented badges acquired the normal
skin colour again and the improvement lasted in an
irreversible way for about 4 months till the
disappearing of all of the badges. No skin disorder
of this patient was noted after such a period and
during 10 months of the observation.
EXAMPLE 3: patient C.A., man, 33 years old,
single, engineer
Diagnosis: psoriasis seborrhoica, chronic
pyelonephritis.
Anamnesis: psoriasis was diagnosed 7 years ago
during the military service. The badges appeared on
the forehead near the hair and then all of the
scalp was covered with scales. Usually, every 2
months there were exacerbations of the psoriasis.
After a treatment with mercury ointments there was
only a temporary improvement, yet the badges did
2S not disappear and became permanent.
wosst22346 2 1 6 0 ~ 1 pcTAsssloo282
The patient, at the admission at the hospital
complained an intense itch, peeling and the
presence of badges on his scalp and of the "crown"
on his forehead.
The purple crown of the forehead measured
16x3.8 cm2.
The whole surface of the scalp was covered
with the geografica form of psoriasis.
The largest and thickest badqes were placed
10 heh i n~ the ears. The patient was deeply depressed
too.
Treatment with ceruletide ~iethyl a~ine salt
The patient was treated with a single
injection of 3.0 ~g of ceruletide diethyl amine
salt.
The patient noted an improvement of the sleep
and itch, and the stabilisation of the moral state.
During one week the badges became less thick
and brown. 3 weeks later the badges behind the ears
became thin and pale.
Large spaces appeared in the crown which began
to divide into single pieces. The skin improvement
lasted for 3 months.
A second injection of 2.7 ~g was done after 4
months from the first one. A significant decrease
wossl223~6 PCT~B95/00282
~1602~1
of the peeling was obtained and the crown went
paler.
The badges behind the ears were reduced and
became pale and thin.
The treatment was continued and after about 12
months no aggravation in his state, which was
superimposable with the one resulting from the
latest treatment, was noted.
EXAMPLE 4: The patient S. Sh., 22 years old,
single, university student, plays basketball and
track-and-field sports.
Diagnosis: psoriasis guttata accompanied by
gastritis.
Anamnesis: psoriasis badges appeared first 14
lS months after the begi nni ~q of the treatment caused
by an heavy stress provoked by a conflictual state.
Exacerbations occurred in autumn. Moreover,
new badges appeared when pastry, cakes and other
products of the same kind, having a high caloric
value, were eaten.
The patient cured himself with hormonal,
salicylic and sulphurous ointments, vit~ins,
quartz and sun bathing.
W095/22346 216 ~ PCT~B95100282
Il
The badges went pale and disappeared leaving
depigmented stains, yet they reappeared some weeks
later.
The last course of treatment - with a combined
use of vitAmins, 2% salicylic ointment, quartz and
pine bathing was effected after 2 months from the
beginning of the treatment with ceruletide.
Several badges on his face, legs, arms, chest
and back were noted at the admission at the
hospital.
On the face small badges mainly disposed along
the hairline. On the legs: small badges,
disseminated on the back and on the side of tibiae
and some badges on the knees.
On the arms: 5-6 badges, having a small
diameter, for each shoulder.
On the chest: 6 badges having a diameter up to
1,5 cm; on the back 10 small badges mainly disposed
in lateral upper zones. The patient complained
periodical itch attacks, irritability, insomnia.
Treatment with ceruletide diethyl ~mi ne salt
After the injection of a single dose of 4.0 ~g
ceruletide diethyl amine salt, the patient noted a
remarkable improvement of sleep, itch became less
bothersome, his moral state improved.
W095/22346 ~ 16 015 ~ 12 PCTAB95/00282
During the first 2-3 days next to the
application of the drug, a slight exacerbation of
the disease occurred: the number of the badges
increased a few. Yet, after two weeks, all the
badges went soft and pale, the scales disappeared.
Then, the badges became paler and thinner, totally
disappearing after about 1 month and a half the
beginning of the treatment.
After the treatment with ceruletide diethyl
amine salt no relapses of the disease were noted
during the next 14 months.
