CA2160251A1 - Use of ceruletide diethyl amine salt in the treatment of psoriasis - Google Patents

Abstract

The use of ceruletide diethyl amine salt in the treatment of psoriasis is claimed.

Description

~ ~ 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 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 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~

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.

Claims (4)

13

1. The use of the decapeptide ceruletide (Takus) diethyl amine salt for the preparation of a medicament useful for the treatment of psoriasis.

2. The use according to claim 1, characterized in that the ceruletide diethyl amine salt is administered to the patient in a single dose of 2.5-5.0 µg.

3. The use according to claim 1, characterized in that the ceruletide diethyl amine salt is administered to the patient in two subsequent applications of 2.5-5.0 µg, considering the individual sensibility of the patient.

4. A composition for the treatment of psoriasis, characterized in that it comprises the decapeptide ceruletide diethyl amine salt as pharmaceutical active ingredient.