HRP20020201A2 - Pharmaceutical compositions for treating psoriasis - Google Patents

Description

This invention relates to pharmaceutical mixtures based on 1,2-bis(3,5-dioxopiperazin-1-yl)-propane and their pharmaceutically acceptable salts.

1,2-bis(3,5-dioxopiperazin-1-yl)-propane was obtained from the formula

[image]

and can exist in the d-isomer form, the 1-isomer form, and the racemic dl-form.

The racemic dl-form of 1,2-bis(3,5-dioxopiperazin-1-yl)-propane is known as resoxane. Compounds of this type belong to the bis-dioxopiperazine family, which have been known for a long time, especially as anti-tumor agents. This type of compounds, their use and preparation are described in, for example, GB-A-1 234 935, GB-A-1 374 979, US-A-4 275 063, EP-A1 491 053, EP-A1 256 137, EP-A1 230 474, EP-A2 014 327 and EP-A1 125 475.

Bis-dioxypiperazines are lipophilic derivatives of EDTA (ethylene diamine tetraacetic acid), a substance known as a chelating agent. As such, they act by chelating iron, thereby reducing the production of specific oxygen radicals. Bis-dioxopiperazines promote topoisomerase II inhibitory activity, which is thought to be responsible for the antitumor activity of these drugs. The D-enantiomer of razoxane is known as dexrazoxane. The current clinical use of dexrazoxane is to prevent doxorubicin-induced heart disease in patients with metastatic breast cancer.

Dexrazoxane is commercially available as the hydrochloride salt. In Europe, dexrazoxane.HCl is available from Chiron, Inc. under the registered trademark Cardioxane, while in the US it is available from Pharmacia Upjohn under the registered trademark Zinecard. A discussion of the chemical, biological, and clinical aspects of dexrazoxane and other bis-dioxopiperazines can be found in Current Medicinal Chemistry (1998) 5, 1-28. GB-A-1 234 935 which is one of the oldest publications on bis-dioxopiperazines and describes their preparation through cyclization of the corresponding tetracarboxamido methyl derivatives through heating together with polyphosphoric acid. The therapeutic spectrum of these drugs includes certain forms of tumors, including leukemia, and certain malignant forms of proliferative diseases.

Two methods are mainly described for the preparation of dexrazoxane (US 3 941 790). In the first method, 1,2-diaminopropane tetraacetic acid and formamide are heated together until the cyclic product is obtained. In another method, the corresponding tetramide of the above-described tetraacetic acid is heated in polyphosphoric acid or phenol, likewise until cyclization of the compound is obtained (see the aforementioned GB-A-1 234 935).

Other methods of preparing dexrazoxane are known, for example described in US Pat. No. 4 764 614 or in EP-A-0 330 381.

Psoriasis is a chronic skin disease characterized by rapid progression and inflammation. The cause of psoriasis is known, but recent research has shown that it is an auto-immune disease. Psoriasis is a serious and unpleasant condition for which there is no cure, and certain treatments cannot be applied to every individual.

Psoriasis can be extremely painful, but the pain comes on top of extensive skin damage. Emotional complaints are also included. People suffering from this disease experience physical limitations, physical disfigurement, frustration, fear and depression. In extreme cases, there is a loss of self-esteem that leads to the complete exclusion of a person from social life. Different types of means for temporary pain relief are available to patients, but with different results for each individual patient. Treatment and medication are often just a waste of time and money, but one thing is certain: symptoms may come and go, but they almost always come back. It is a lifelong disease.

Psoriasis is treated using what is often called the "1,2,3" approach. Level 1 is surface treatment, level 2 is phototherapy and level 3 is systemic treatment. Medicine currently prescribes systemic treatment using the immunosuppressants methotrexate and cyclosporin A, hydroxyurea and retinoids.

Methotrexate and cyclosporine A have unpleasant and potentially dangerous side effects. In addition, after each such treatment, the patient still remains with recurrent psoriasis, and because each individual patient responds differently to treatment, it would be beneficial to have other additional means of treatment.

In 1976, D.J. Atherton (Lancet ii, 1296, 1976) first proposed the use of racemic razoxane (ICRF-159) for the treatment of psoriasis. A review of the therapeutic use of razoxanes in psoriasis can be found in the British Journal of Dermatology (1980) 102, 307. The drug had a relatively good effect and a good degree of tolerance, but some unpleasant side effects appeared and certain toxicities were noted. Therefore, administration of the drug was recommended only in a strictly controlled condition. Horton and Wells (British Journal of Dermatology (1983) 109, 669-673) again report relatively good treatment success with razoxane, however, a significant number of patients discontinued treatment due to relatively many adverse side effects. The most commonly observed side effect was neutropenia, a potentially fatal depletion of neutrophils (a subunit of leukocytes), which was reported to occur in a number of patients on minimal doses, even those insufficient to control psoriasis. Other side effects were alopecia, nausea, diarrhea, epistaxis, leg ulcers, lethargy, headaches, and squamous epithelioma.

Due to these and other complications that arose after chronic treatment, razoxan was not developed further, and today it is not recommended for the treatment of psoriasis. Until now, therefore, the known facts about razoxane were that it cannot be used for safety reasons despite its effectiveness in the treatment of psoriasis.

Surprisingly, it has now been shown that the d-enantiomer of 1,2-bis(3,5-dioxopiperazin-1-yl)-propane, dexrazoxane, can be used by itself to treat psoriasis with complete safety and efficacy. No serious adverse events have been observed with clinical treatment to date, with the vast majority of patients not suffering from neutropenia, and no cases of vomiting, nausea or diarrhea have been reported.

In accordance with the present invention, a new pharmaceutical composition for the treatment of psoriasis contains the active compound dexrazoxane, or their pharmaceutically acceptable salts, together with a pharmaceutically acceptable carrier and/or excipient.

The invention also includes a method of treating psoriasis in a patient, comprising administering to the patient a therapeutically effective amount of dexrazoxane, 1,2-bis(3,5-dioxopiperazin-1-yl)-propane d-isomer, a compound of the formula

or their physiologically acceptable salts.

The invention is further described below with reference to accompanying figure 1, which is a graphical representation of the baseline value (n=7) of the Psoriasis Area and Severity Index (PASI) according to the treatment protocol with three cycles of dexrazoxane administration.

The method may comprise administration of dexrazoxane by injection or infusion (or other internal administration, for example by oral route) at a daily dosage, for example between 250 mg and 1750 mg, and one suitable protocol comprises administration of dexrazoxane in increased doses, for example at the first daily dosage in the initial time period of up to 5 days, the second daily dosage for the second period of up to 5 days for the third daily dosage of up to, for example, 5 days. The initial, second and third periods differ in some treatment protocols. For an adult, the first day of dosing is usually 250 mg to about 750 mg (eg about 500 mg), the second day the dose is usually about 250 mg to 1250 mg (eg about 1000 mg), and the third day a dose of usually about 1250 mg to 1750 mg (eg about 1500 mg).

In any case, the most preferred protocol for the internal, i.e. oral administration of dexrazoxane, involves the administration of dexrazoxane at equal intervals, for example between 5 and 20 days apart, most often 8 to 16 days, and most preferably 10 to 14 days apart days, eg 12 days. As indicated earlier, the administration period may be only two successful days, in which case dexrazoxane may be administered on all of those days or only on some of those days. Particularly preferred protocols comprise three separate application periods, for example, two days without interruption and/or separately at 12-day intervals; therefore, the protocol can contain the three cycles that appear in Figure 1. The application of the protocol can be repeated if necessary, for example, after a period between one month and one year and more. Oral administration is suitable for infusion or injection, and dexrazoxane is usually (but not always) given as a salt.

The dosage may vary, for example, be increased, in accordance with the needs of the treatment. In particular, the dosage can be increased after the first period of drug administration according to the protocol described in the previous paragraph, if the patient's initial reaction is inappropriate. It is common for an adult to be given a dose of about 250 mg to about 750 mg each day for the first two days of treatment, after which the dose may be maintained or increased (eg, to about 750 mg to about 1250 mg). After the second period of administration, the dose can be maintained or, if necessary, increased (or even reduced) for the third period of administration. Dosage may or may not vary in 500 mg increments.

The mass of dexrazoxane and the mass percentage stated in this application refer to dexrazoxane hydrochloride, i.e. it refers to dexrazoxane as the hydrochloride salt. If any other alternative form is used, an appropriate adjustment must be made based on the relative molecular weight of the two forms. Similarly, doses must be adjusted appropriately for the treatment of children.

In one class of method, therefore, dexrazoxane is administered intravenously or otherwise by injection or infusion. In current practice, solutions for injection or infusion are prepared by reconstitution of lyophilized dexrazoxane prior to administration. The lyophilizate may be packaged in an amount corresponding to a unit dose to be used in a package containing about 250 mg, from about 750 mg to about 1250 mg or about 1750 mg, all of which are included in the invention. The invention also includes the use of dexrazoxane in the preparation of liquid preparations of dexrazoxane for a preparation immediately ready for use, and the use of such a liquid preparation ready for use (solution).

In another type of procedure, dexrazoxane is administered topically, through the skin or through the skin, eg in the form of an ointment, lotion or patch. Other methods involve oral administration of dexrazoxane, for example in tablet form. Dexrazoxane can be given in the form of suppositories (suppositories). Alternatively, dexrazoxane is administered as a topical preparation, such as an ointment, cream or gel. The concentration of dexrazoxane is not critical. However, some preparations for local use contain at least 0.1 wt% dexrazoxane, and more often contain from 0.25 wt%, and especially 0.5 wt% to 5 wt% or more of dexrazoxane. One type of preparation contains 1-2% by weight of dexrazoxane. The invention includes compositions adapted for local administration to the exclusion of oral and peroral administration or administration by injection or infusion. Preparations for topical application are conveniently packaged in tubes of up to 100 g, with instructions to use them for the treatment of psoriasis.

Preparations for local use may, for example, contain conventional carriers. By way of non-limiting examples, the ointments may contain water and one or more hydrophobic carriers selected from liquid paraffin, polyoxyethylene alkyl ether, propylene glycol and white petrolatum. Cream mixture carriers are typically based on water and white petrolatum, combined with glycerol and a number of other ingredients, eg one or more glycerin monostearate, PEG-glycerin monostearate and cetyl stearyl alcohol. Gels can be formulated using isopropyl alcohol and water, conveniently in combination with minor components, for example one or more glycerol and hydroxyethyl cellulose.

Dexrazoxane can be used in combination therapy, for example with non-steroidal anti-inflammatory drugs, TNF inhibitors or vitamins. The invention therefore includes products, in particular compositions for topical application, containing dexrazoxane and an agent useful for treating psoriasis or alleviating symptoms as a combined composition for simultaneous, separate or sequential use in the treatment of psoriasis. The product can be a preparation for local application containing two or more active agents in combination.

During the clinical trial, signs of improvement were accelerated, and were observed even in the most resistant cases with a long history of psoriasis. The itching disappeared within a few hours after the first application and completely disappeared after the next dose. The progression of the disease is reduced, the unpleasant smell disappears, the width of the affected area is significantly reduced and the patient has no visible signs of arthralgia.

The patient shows significant subjective and objective reactions such as 25-30% regression of the skin lesion, without the occurrence of known side effects of razoxane.

The preferred preparation is a sterile solution for injection or infusion, but ointment, lotion, oral forms, plasters and suppositories (suppositories) can also be used.

The invention is illustrated in the following examples:

Clinical trial of the effectiveness of dexrazoxane:

EXAMPLE 1

The patient, a 55-year-old man, suffered from psoriasis for 20 years in his medical history. The disease started after psychological stress (loss of a close person) with itching on the hairy part of the head. At the very beginning of the disease, the patient was intensively treated with vitamins B12, B6, B2, and calcium. The patient suffered from artificially induced hypothermia with pyrogen injection, methotrexate, different ointments (eg salicylic ointment) under the supervision of a doctor in a specialized clinic. Despite the treatment, psoriatic itching spread to the abdomen, upper and lower limbs, accompanied by general itching. The itching did not stop. This caused the development of other diseases, such as the appearance of high blood pressure of the II degree and chronic cholecystopancreatitis.

During the first examination, the patient complained of itching all over the body (which caused insomnia) and pain in the joints (mainly the knees). The skin on the back, groin, chest and arms was covered with a papular and postular rash with a white layer (desquamation). A similar but slightly less intense rash also appeared on the legs. The patient's general condition, hematological and biochemical profile were within normal limits.

On the first and second day of the treatment cycle, the patient received the first dose of Cardioxan® (dexrazoxane.HCl) of 500 mg every day intravenously by infusion. On the fifteenth (15th) day, the patient noticed the disappearance of itching a few hours after the first application of Cardioxan®. The itching practically disappeared after the next dose of Cardioxan® at 1000 mg on the 16th day. The patient noticed the cessation of the spread of itching, unpleasant odor, hypernia and rash, and the complete disappearance of arthralgia. The patient slept well for the first time after a long period since he got sick. The effect was still the same on the 29th and 30th days when the patient was given the last injection of Cardioxan® of 1500 mg each.

During the last examination on the 29th day, the patient noticed a reduction of the rash, the disappearance of some lesions and the appearance of normal skin surfaces (up to 2 cm in diameter, especially on the lower edges). A total reduction of 25%-30% of skin lesions was diagnosed. The itching, although it returned briefly about 1.5 weeks after the first two injections, did not appear after the third and fourth injections, nor did the arthralgia appear. There were no adverse events after any of the injections.

EXAMPLE 2

This patient, a 50-year-old man, had suffered from psoriasis for 25 years. The rash first appeared on the head and right upper limb, and spread to the abdomen and later the upper limbs. The patient was treated similarly to the patient described in Example 1. Additionally, this patient was treated with ultrasound therapy, peloids, sulfur-hydrogen bath, but without long-term effect. The patient had no accompanying complaints except for asthenia, sinus arrhythmia and left ventricular hypertrophy. The skin on the back, coccyx and shoulders was covered with a papular rash, severe skin damage. The area of the side of the chest and lower limbs were mostly not affected by the rash. Skin lesions covered about 50% of the total body surface. The patient did not complain of itching.

The patient was given 6 intravenous infusions with Cardioxan® according to the following order:

On the first day 1 and on the second day 500 mg of Cardioxan®

15 and 16 days per 1000 mg of Cardioxan®

and 29 and 30 days per 1500 mg of Cardioxan®.

On the day of examination on the 15th and 29th day, the patient noticed a slight decrease in the rash on his back. No changes were observed in the rest of the damaged area. There were no side effects.

EXAMPLE 3

This patient, a 37-year-old woman, suffered from the disease for 16 years in her medical history, which manifested itself after an abortion and mental stress. The psoriatic rash appeared on the hairy part of the head and neck, and spread over the whole body. The patient was treated by exposure to the sun's rays (tanning), but without a long-term effect. The patient was hospitalized four times in order to undergo therapy with vitamins, calcium, and various fats. After a period of time from the beginning of the stressful period due to the loss of a close person, the patient's condition worsened, and the disease progressed with the appearance of skin damage and a rash that covered almost the entire body. The patient also suffered from allergic bronchial asthma in her medical history.

On the first day of examination, the patient suffered from a continuous psoriatic papular rash with severe damage to the anterior abdominal wall (in the area below the breasts), in the groin area, lumbosacral area, gluteal area and lower limbs, and difficulty breathing (asthmatic bronchitis). A deterioration in the number of eosinophils was also observed.

The patient received 6 intravenous infusions of Cardioxan® according to the protocol from Example 2. During the examination on the second day, a complete cessation of itching was noticed 2 or 3 days after the first injection of Cardioxan®. The rash has completely disappeared on the lower part of the abdomen as well as in the upper quadrant of the groin. There were no negative consequences after the injection of Cardioxan®, except for a slight pain in the veins during the injection.

On the 30th day examination, an 80% regression of the rash was observed in the patient, with reduced depigmentation in the lumbosacral area and legs. Still no itching. There were no negative consequences, despite the patient's current allergic condition.

EXAMPLE 4

The efficacy and tolerability of dexrazoxane in patients with intractable psoriasis has been evaluated in clinical studies.

After the study, certain patients received 500 mg of Cardioxan® by intravenous infusion every other day. They were observed 7 and 14 days after the first day of treatment. Patients then underwent a second cycle of treatment, consisting of either 500 mg of Cardioxan® by intravenous infusion on each of two subsequent days (days 15 and 16, in this case), if the desired response was achieved, or 1000 mg of Cardioxan® ® by intravenous infusion, every following day (days 15 and 16, in this case), if the desired reaction did not occur.

The third treatment cycle is applied after the same time interval (days 29 and 30, in this case). Patients who have shown an appropriate reaction receive the same dose as they received in the second cycle, while the patient, in whom no change in condition is observed, is administered a dose of 1500 mg.

The primary efficacy parameter is measured by the percentage of lesion area and lesion severity sampled by psoriasis, as indicated by the Standard Assessment of Psoriasis Area and Severity Index (PASI).

Seven patients were included in the study and all patients completed it within a period of two weeks. At the start of treatment, PASI scores ranged between 23.1 and 44.1, with an average score of 31.9. Most patients did not respond to treatment, except for one patient, who was absolutely resistant to therapy. At the end of the third treatment cycle, the PASI-scores ranged between 3.4 and 29.7, with an average score of 11.4.

After 11 weeks from the start of therapy, the average reduction in PASI-scores was 65% with a maximum reduction of 88%, and one case of resistance. The tolerance of the treatment was excellent, and there were no serious adverse effects. Furthermore, therapy with Cardioxan® resulted in better and faster relief from symptoms associated with psoriatic arthritis, when compared to treatment with cyclosporine A (used in standard clinical treatment).

The results are presented in Table 1 and graphically presented in Figure 1.

TABLE 1: Effect of treatment with Cardioxan® on the Psoriasis Area and Severity Index (PASI)

________________________________________________________________

PASI score and patient number/initial

Visit No. 1/HH 2/MR 3/MZ 4/PH 5/PZ 6/FJ 7/DJ

tl 23.1 43.6 29.8 27.0 29.1 44.1 26.6

t4 11.3 36.3 18.4 18.6 16.9 24.8 23.6

t7 7.7 23.1 11.6 13.5 9.9 20.3 23.0

t9 6.5 15.6 9.7 10.8 9.3 15.6 21.8

t10 6.5 12.3 7.1 12.0 7.8 15.6 28.5

t11 5.6 14.0 6.5 5.2 3.4 15.3 29.7

average PASI score at the beginning of treatment (n=7): x = 31.9

average PASI score after 7 weeks (n=7): x = 11.4

average reduction in PASI score (n = 7): 65%

Of the 7 treated patients, only one was diagnosed with mild, reversible leukopenia (approximately 3x10E9 cells per liter, classified as grade I toxicity according to World Health Organization criteria) after the first week of treatment. This neutropenia disappeared after the second week, and the leukocyte count was still normal. All other patients had normal white blood cell counts. The degree of toxicity was in accordance with the criteria of the World Health Organization: grade 0 (non-toxicity, number of more than 4x10E9 leukocytes per liter), grade 1 (mild) to grade 4 (highly harmful). No cases of nausea, vomiting, or diarrhea were recorded.

The most recent information is that most patients recover from the disease after the last injection. Three patients were not completely cured, but the disease appears in such a mild form that it can be further treated with the usual means, such as ointments. All these patients previously suffered from the most severe form of psoriasis that was incurable by other treatment methods.

In a separate study of three patients with intractable psoriasis that had been progressing for some time, one patient still progressed, as there were no lesions or other symptoms after one year. This patient, who previously suffered from an incurable and most severe form of psoriasis, can be treated with the usual palliatives. Therefore, dexrazoxane can potentially eliminate psoriasis for a long time with a low degree of unwanted phenomena.

EXAMPLE 5

The infusion solution is prepared:

Cardioxan® is available in a 36 ml brown glass bottle. Each vial contains 500 mg of lyophilized active substance, dexrazoxane hydrochloride acid salt. To reconstitute the ingredients, each vial is dissolved in 25 ml of distilled water for injection. The ingredients will dissolve in a few minutes with slow shaking. The pH of the resulting solution is approximately pH 1.6.

For infusion, the solution must be further diluted. Sodium lactate UP (0.16 M) or Ringer-Lactate BP for infusion are preferred. Both solutions provide an infusion solution with an acceptable pH.

[image]

EXAMPLE 6

A tablet was prepared from the following mixture:

Mg/tablets

Cardioxan® 100 mg

Avicel® (microcrystalline cellulose) 16 mg

starch 9 mg

hydroxypropylmethyl cellulose 3 mg

magnesium stearate 1 mg

polyvinylpyrrolidone 0.6 mg

colloidal silicon dioxide 0.3 mg

Half of the total amount of hydroxypropylmethyl cellulose, polyvinylpyrrolidone and a sufficient amount of water are mixed together until they dissolve (binding solution). Cardioxan®, starch, and the rest of the hydroxypropylmethyl cellulose were mixed in a granulator and mixed for 10 minutes. The granulation process begins with the spraying of the binding solution. After spraying and mixing, the product is dried in the same device and released when the water content is below 2.8-3.0%. The granulate is passed through an oscillatory granulator equipped with a 1.2 mm stainless steel monitor. The granulate is mixed with starch, microcrystalline cellulose and colloidal silicon dioxide for 20 minutes under rotation. Magnesium stearate was added and mixed with the granulate. The final product was compressed to 130 mg on a circular tableting unit equipped with a 10 mm diameter lenticular punch.

EXAMPLE 7

The ointment was prepared from the following mixture:

g/100 g of fat

Cardioxan® 1.5 g

liquid paraffin 10 g

polyoxyethylene-20-stearyl ether 15 g

propylene glycol 5 g

white vaseline 40 g

purified water 28.5 g

Cardioxan® is reconstituted again in cold water. The other ingredients are melted at 60ºC and mixed. Cardioxan® is added and the product is stirred until it cools.

EXAMPLE 8

The cream is prepared from the following mixture:

g/100 g of cream

Cardioxan® 1 g

glycerin monostearate (Tegin M®) 4 g

PEG-20-glycerin monostearate (Tagat S2®) 7 g

cetylstearyl alcohol 6 g

grain paraffin 7.5 g

white vaseline 25 g

glycerol 85% 10 g

magnesium sulfate heptahydrate 0.5 g

purified water 39 g

Glycerin monostearate, PEG-20-glycerin monostearate, cetyl stearyl alcohol, paraffin and petroleum jelly are heated to 60ºC and mixed. A small part of the water is gently heated and cooled to 60ºC, magnesium sulfate and glycerol are added and mixed. Cardioxan® is reconstituted again in another part of water and added to the solution. Now the two phases are emulsified using an emulsifier, and after cooling, a homogeneous cream is obtained.

EXAMPLE 9:

A gel was prepared from the following mixture:

g/100 g of gel

Cardioxan® 1.2 g

isopropyl alcohol 20 g

glycerol 100% 2 g

hydroxyethyl cellulose 1.8 g

purified water 75 g

Half of the total amount of water and glycerol are heated to 50ºC; hydroxyethyl cellulose is added and mixed until a homogeneous gel is obtained. Cardioxan® is reconstituted again with the rest of the water and added with continuous mixing. The gel is cooled to 25ºC, isopropyl alcohol is added and the mixture is stirred under vacuum until a homogeneous gel is obtained.

Claims (1)

1. Use of dexrazoxane, 1,2-bis(3,5-dioxopiperazin-1-yl)-propane d-isomer for the production of a drug for the treatment of psoriasis, characterized in that it is obtained from a compound of the formula [image] or their physiologically acceptable salts. 2. Use of Claim 1, characterized in that the physiologically acceptable salt is dexrazoxane.HCl. 3. The use of Claim 1 or 2, characterized in that the drug is for injection or infusion. 4. Use of Claim 3, characterized in that the medicine contains a powder for reconstitution in a solution before injection. 5. Use of Claim 1 or 2, characterized in that the drug is applied locally, through the skin or through the skin. 6. Use of Claim 5, characterized by the fact that the drug can be in the form of an ointment, lotion or patch. 7. Use of Claim 1 or 2, characterized in that the medicine can be in oral form. 8. Use of Claim 1 or 2, indicated by the fact that the medicine can be in the form of a suppository (suppository). 9. The use of Claim 3 or 4, characterized in that the drug can be in the form of a dosage unit and contains between 250 mg and about 750 mg (eg 500 mg) of dexrazoxane, calculated as dexrazoxane hydrochloride. 10. The use of Claim 3 or 4, characterized in that the drug may be in dosage unit form and contain between 750 mg and about 1250 mg (eg about 1000 mg) of dexrazoxane calculated as kesrazoxane hydrochloride. 11. The use of Claim 3 or 4, wherein the vial may be in dosage unit form and contain between about 1250 mg and about 1750 mg (eg about 1500 mg) of dexrazoxane calculated as dexrazoxane hydrochloride. 12. The use of Claim 11, characterized in that the drug can be in the form of a preparation for local administration in which dexrazoxane is present in the drug in a concentration of about 0.1 wt% to about 5 wt% calculated as dexrazoxane hydrochloride. 13. Use of Claim 1 or 2, indicated by the fact that the drug can be a preparation for injection or infusion and is for use on adults according to a protocol that contains: (a) administering the drug by infusion or injection in a dose of between about 250 mg and 750 mg calculated as dexrazoxane hydrochloride; (b) on the following day of administration of the drug by infusion or injection in a dose of between 750 mg and 1250 mg calculated as dexrazoxane hydrochloride; (c) on the following day administering the drug by infusion or injection in a dose between about 1250 mg and about 1750 mg calculated as dexrazoxane hydrochloride. 15. The product, in particular, contains a preparation for local and oral administration, indicated by the fact that it contains dexrazoxane or their physiologically acceptable salt and an agent useful for treating psoriasis or eliminating symptoms as a combined preparation for simultaneous, separate or sequential use in the treatment of psoriasis. 16. A method of treating psoriasis in patients, characterized by the fact that it consists of administering to the patient an effective amount of dexrazoxane, 1,2-bis(3,5-dioxopiperazin-1-yl)-propane d-isomer, compound of the formula [image] or their physiologically acceptable salts. 17. The method according to Claim 16, characterized in that dexrazoxane is administered together with a physiologically acceptable diluent, carrier or excipient. 18. The method according to Claim 16 or 17, characterized in that the physiologically acceptable salt is dexrazoxane.HCl. 19. The method according to Claims 16 to 18, characterized in that the dexrazoxane is administered by injection or infusion. 20. The method according to any of Claims 16 to 18, characterized in that the dexrazoxane is administered locally, through the skin and through the skin. 21. The method according to Claim 20, characterized in that the dexrazoxane is in the form of an ointment, lotion or patch. 22. The method according to any one of Claims 16 to 18, characterized in that the dexrazoxane is administered orally. 23. The method according to any one of Claims 16 to 18, characterized in that the dexrazoxane is in the form of a suppository (suppository). 24. A method according to any one of Claims 16 to 23, characterized in that the patient is an adult, and the method comprises the step of administering dexrazoxane via infusion or injection in a dose between 250 mg and about 750 mg calculated as dexrazoxane hydrochloride. 25. The method according to any one of Claims 16 to 24, characterized in that the patient is an adult, and the method comprises the step of administering dexrazoxane by infusion or injection in a dose between about 750 mg and about 1250 mg calculated as dexrazoxane hydrochloride. 26. The method according to any one of Claims 16 to 25, characterized in that the patient is an adult, and the method comprises the step of administering dexrazoxane by infusion or injection in a dose between 1250 mg and about 1750 mg calculated as dexrazoxane hydrochloride. 27. The method according to any one of Claims 16 to 23, characterized in that the patient is an adult, and the method consists of steps (a) administering dexrazoxane by infusion or injection at a dose of between about 250 mg and about 750 mg calculated as dexrazoxane hydrochloride; (b) at the next administration of dexrazoxane by infusion or injection in a dose between about 750 mg and about 1250 mg calculated as dexrazoxane hydrochloride; (c) at the next administration of dexrazoxane by infusion or injection in a dose between 1250 mg and about 1750 mg calculated as dexrazoxane hydrochloride. 28. The method according to Claim 16, characterized in that the dexrazoxane is administered locally. 29. The method according to Claim 28, characterized in that the dexrazoxane is administered as a preparation for local administration containing about 1 wt% to about 2 wt% dexrazoxane calculated as dexrazoxane hydrochloride. 30. A method for the preparation of a medicine for the treatment of psoriasis, characterized in that it contains the preparation of dexrazoxane or their physiologically acceptable salts in such a medicine. 31. The method from Claim 30, characterized in that it further includes the implementation(s) of one or any of Claims 2 to 14.