KR20020035131A - Use dexrazoxane for treating psoriasis - Google Patents

Abstract

The present invention relates to the use of dexrozaic acid or a physiologically acceptable salt thereof as a d-isomer of 1,2-bis (3,5-dioxopiperazin-1-yl) propane for the preparation of a medicament for the treatment of psoriasis.

Description

USE DEXRAZOXANE FOR TREATING PSORIASIS USE OF DEXURA ACID

1,2-bis (3,5-dioxopiperazin-1-yl) propane has the following formula:

, And there are d-isomer, 1-isomer and dl-type racemate.

The dl-racemate of 1,2-bis (3,5-dioxopiperazin-1-yl) propane is known as razoxane. This class of compounds has long been a member of the bis-dioxopiperazine family, especially known as anticancer agents. Compounds of this family, their uses and methods of preparation are described, for example, in GB-1 234 935, GB-1 374 979, EP-A1 491 053, EP-A1 256 137, EP-A1 230 474, EP- And EP-A1 125 475.

Bis-dioxopiperazine is a lipophilic derivative of EDTA (ethylenediaminotetraacetic acid) known as a chelating agent. Bis-dioxopiperazine exhibits a topoisomerase II inhibitory activity possibly involved in the anticancer activity of these drugs. As bifunctional alkylating agents, these agents cause the arrest of mitosis during G2 or early prophase of the cell cycle. Dexrazoic acid is currently used clinically to prevent doxorubicin induced heart disease in patients with metastatic breast cancer. Dextrazaic acid is a hydrogen chloride salt and is marketed by Chiron, Inc. as a registered trademark Cardioxane. The chemical, biochemical and clinical considerations of dexlazic acid and other bis-dioxopiperazines can be found in Current Medicinal Chemistry (1998) 5, 1-28. GB 1 234 935 describes one of the earliest publications on bis-dioxopiperazine which is prepared by cyclization of the corresponding tetracarboxamidomethyl derivatives by heating with polyphosphoric acid. Therapeutic ranges of these agents include certain forms of cancer, including leukemia, and certain non-malignant forms of proliferative diseases.

There are mainly two methods for preparing dexlazo acids (US 3 941 790). In the first method, 1,2-diaminopropane tetraacetic acid and formamide were heated together to provide the ring product. In the second method, the corresponding tetramide of the tetraacid is heated in polyphosphoric acid or phenol to induce the cyclization of the compound (see GB Patent No. 1 234 935).

Other methods for the preparation of dexlazoic acid are given, for example, in U.S. Pat. No. 4,764,614 or EP-A-0 330 381.

A method of making a lyophilized composition containing stable and less sensitive to light dexlazoic acid is described in detail in U.S. Patent No. 5,760,509.

Psoriasis is a chronic skin disorder characterized by scaling and inflammation. The cause of psoriasis is unknown, but recent studies point out that it may be an autoimmune disease. Psoriasis is a serious and unpleasant symptom that has no cure to cure all the symptoms of each individual.

Psoriasis can be very painful, but the pain is not limited to the skin but also involves emotional pain. This gives people physical limitations, uncomfortable looks and persistent daily management that always takes a long time. It is common to feel shyness, atrophy, fear and atrophy. In extreme cases, loss of self-esteem can lead to total alienation from society. There are various temporary mitigation methods and various success rates. These therapies and medicines are often time consuming and expensive, but one thing is certain that the symptoms recur and improve, but they always recur. This is a lifelong disease.

Psoriasis is treated using the so-called "1-2-3" method. Step 1 is a topical treatment, Step 2 is a light treatment and Step 3 is a systemic treatment. The drugs currently prescribed for systemic treatment are the immunosuppressants methotrexate and cyclosporine, hydroxyurea, and retinoids.

Methotrexate and cyclosporine have unpleasant and potentially dangerous side effects. It would also be highly welcome to add new treatments to the list of treatments because all of these treatments lead to recurrence of psoriasis and many patients respond differently to different treatments.

First, in 1976, DJ Atherton ( Lancet , ii, 1296, 1976) proposed the use of razoside racemate for the treatment of psoriasis (1CRF-159). A review of the therapeutic use of razosans for psoriasis can be found in the British Journal of Dermatology (1980) 102, 307. Drugs have relatively good pharmacological and tolerance properties, but have somewhat unpleasant side effects and certain toxicities have been mentioned. Therefore, administration of medicines is only recommended under strictly controlled conditions. Horton and Wells ( British Journal of Dermatology (1983) 109, 669-673) reported relatively good outcomes for treatment with razaic acid, but many reported that the treatment was discontinued due to relatively serious side effects. The most common side effect is neutropenia, a potentially fatal deficiency in neutrophils (a part of white blood cells), and has been reported in many patients in an amount that is insufficiently low in psoriasis. Other side effects included alopecia, nausea, diarrhea, nosebleeds, ulceration of the legs, coma, headache, and scaly epidermoid tumors.

Due to these and other complications that arise after chronic administration, razoesan has not been further developed and is not recommended for the treatment of psoriasis today. So far, what is known about Rajasan is that it can not cure psoriasis safely and effectively.

The present invention relates to a pharmaceutical composition based on 1,2-bis (3,5-dioxopiperazin-1-yl) propane and its pharmaceutically acceptable salts.

The invention is further illustrated below with reference to the accompanying Figure 1.

Figure 1 is a graphical representation of the mean value of psoriasis immunity and severity (PASI) (n = 7) over a treatment protocol with dexrazic acid dosing cycles.

Surprisingly, however, it has been found that dexlazoic acid, the d-enantiomer of 1,2-bis (3,5-dioxopiperazin-1-yl) propane itself can treat psoriasis safely and effectively. In addition, our study has shown that treatment results for some patients with the intractable dryness to relief over a period of up to at least one year are truly significant. To date, no serious adverse events have been reported in clinical trials, and most of the patients did not show neutropenia and no cases of vomiting, nausea or diarrhea were reported.

In accordance with the present invention, a pharmaceutical composition for the treatment of psoriasis contains dexlauric acid or a pharmaceutically acceptable salt thereof as an active compound together with a pharmaceutically acceptable carrier and / or excipient.

The invention also encompasses a method of treating psoriasis in a patient comprising administering a therapeutically effective amount of a compound of formula < RTI ID = 0.0 > (3,5-dioxopiperazin-1-yl) propane, which is a compound of formula (I), or a physiologically acceptable salt thereof.

The methods of the present invention include the step of administering dexlauric acid by injection or infusion (or other route of administration) with a daily dose of, for example, 250 mg to 1750 mg and a suitable protocol. Suitable protocols include, for example, a first daily dose for a first period of up to 5 days, for example a second daily dose for a second period of up to 5 days, and a second daily dose for a third period up to, Lt; RTI ID = 0.0 > day < / RTI > The primary, secondary, and tertiary periods may be spaced, preferably spaced one or two days apart. Some treatment protocols may be waived in one of the primary, secondary, or tertiary periods. A first daily dose is typically about 250 mg to about 750 mg (e.g., about 500 mg) and a second daily dose is about 750 mg to about 1250 mg (e.g., about 1000 mg) A third daily dose is generally about 1250 mg to about 1750 mg (e.g., about 1500 mg).

In any case, the most preferred protocol for in vivo administration, e.g. parenteral administration, of dexlactic acid is to administer dexlazoic acid at intervals, for example 5 to 20 days, more usually 8 to 16 days, For example, between 10 and 14 days, for example 12 days. As noted, the dosing period can be daily dosing of dexlazoic acid for two consecutive days. Alternatively, it may be administered for one day, or for a period of more than two days. In this case, dexlazoic acid may be administered only during these periods or for some periods during the period. Particularly preferred protocols consist, for example, of a two-day administration and / or a three-dose administration period with an interval of 12 days. Thus, the protocol may consist of the three cycles shown in Fig. The administration protocol may be repeated as necessary after a period of, for example, one month to one year or more. Parenteral administration is preferably injection or injection, and dexlazoic acid is generally (but not exclusively) administered in the form of a salt.

The dosage may vary, for example, depending on the course of treatment, for example. In particular, if the patient ' s initial response is not adequate, the dose may be increased after the first administration period of the protocol described in the preceding paragraph. Conveniently, the adult is administered a dosage of about 250 mg to about 750 mg daily for the first two days of administration. Thereafter, this dose can be maintained or increased (e.g., from about 750 mg to about 1250 mg). After the second administration period, the dose can be maintained or increased (or even decreased) as needed during the third administration period. The dosage is conveniently, but not exclusively, changed to a level of 500 mg.

The weight and weight percent of dexlazoic acid specified in this specification refers to dexlazanic acid hydrogen chloride. That is, they refer to dexlazo acids in the form of the hydrogen chloride salts. Where alternative forms are used, appropriate adjustments should be made on the basis of the two types of relative molecular weights.

Thus, in one class of methods dexlazoic acid is administered by intravenous injection or other injection or infusion. In the present practice, the solution for injection or infusion is made by reconstituting the freeze-dried dexlazoic acid immediately prior to administration. The lyophilisate is suitably packaged in an amount corresponding to the content to be used, and the package contains about 750 mg to about 1250 mg or 1250 mg to 1750 mg, respectively, of the package. The present invention also encompasses the use of dexlauric acid to prepare a liquid ready-to-use liquid dexlaa acid formulation and the administration of the ready-to-use type liquid formulation (solution).

In another class of methods, dexlazoic acid is administered through the epidermis, transdermal, skin, for example in the form of ointments, lotions or lozenges. Other methods include oral administration of dexlazoic acid, for example, in the form of tablets. Dextra acids may be administered in the form of suppositories. Alternatively, the dexlazo acids may be administered in topical formulations such as ointments, creams or gels. The concentration of dexlazoic acid is not critical. However, some topical formulations contain at least 0.1 wt% dexlauric acid, more preferably 0.25 wt%, especially 0.5 wt% to 5 wt% dexlaa acid. The present invention includes formulations suitable for oral or parenteral administration or administration by injection or infusion. Topical formulations are suitably packaged in tubes up to 100 g with respect to the instructions for treating psoriasis.

Topical formulations may contain, for example, conventional carriers. By way of non-limiting example, the ointment may comprise water and one or more hydrophobic carriers selected from liquid paraffin, polyoxyethylene alkyl ethers, propylene glycol and white petrolatum. The cream phase carrier composition usually consists of water and white petrolatum mixed with minor components such as glycerol and one or more glycerin monostearate, PEG-glycerin monostearate and cetylstearyl alcohol. The gel may be formulated using isopropyl alcohol and water, suitably mixed with trace constituents, such as, for example, one or more glycerol and hydroxyethyl cellulose.

For example, dexlazo acids may be used as a combination therapy with non-steroidal anti-inflammatory agents, TNF inhibitors or vitamins. Accordingly, the present invention encompasses dexrazoic acid and drugs useful for the treatment of psoriasis or alleviation of this symptom, particularly including topical formulations, as a mixed preparation, for simultaneous, separate, or continuous use for psoriasis treatment. The product may be a topical formulation containing a mixture of two or more active ingredients.

During clinical trials, there was a rapid improvement in disease-related symptoms, especially in those with a long history of psoriasis. The itching disappeared within several hours after the first administration and substantially disappeared after the next administration. Decreases were reduced, madescence disappeared, the thickness of the applied area was significantly reduced, and joint pain remained in the patient.

Patients experienced a significant objective and weekly response with a recurrence rate of 25-30% of skin lesions without experiencing known side effects of Rajasan.

The preferred formulations are sterile solutions for injection or infusion, but ointments, lotions, oral forms, lozenges and suppositories may also be used.

The present invention is illustrated in the following examples.

Clinical trials demonstrating the efficacy of dexlazoic acid are as follows.

Example 1

A 55-year-old male patient has a history of psoriasis 20 years. The disease began with the rash of the hair follicle after mental stress (the death of a close person). From the onset of the disease, the patient was treated intensively with vitamin B ₁₂ , B ₆ , B ₂ and calcium. In a professional hospital, under the supervision of a dermatologist, methotrexate, various ointments (eg salicylic ointment) I received artificial hyperthermia treatment. Despite this treatment, the rash of psoriasis spread across the trunk, upper limb, and lower extremities, followed by a remarkable systemic itching. The patient had practically no relief. Associated diseases were grade 2 hypertension and chronic gallbladder cholecystopancreatitis.

In the first trial, the patient complained of itching (causing insomnia) and pain in the large joints (mainly knees) throughout the body. The skin of the back, hips, chest, and arms was covered with a rash and pustular rash of erythema and a white coating (skin rupture). A similar coarse rash was also found in the feet. The general condition, hematologic and biochemical profile of the patient was within the normal range.

On the first and second day of the treatment cycle, the patient received a first dose of 500 mg of cardioxane (dexlazic acid.HCl) daily by intravenous drip infusion. On the 15th day, the patients recorded improvements in vigilance for 6 to 7 hours after the administration of the first cardioxan. On the 16th day, after the administration of 1000 mg of the next dose of cardioxan treatment, the itching substantially disappeared. Improvement in the outcome of the patient, madescence has disappeared, neuropathy has improved, rash has not gone away, and joint pain has disappeared completely. The patient slept comfortably for the first time during a long period of illness. This effect lasted until the 29th and 30th day of the experiment when the patients were given the final injection of 1500 mg of cardiac acid, respectively.

On the 29th day of the experiment, the rash disappeared from the patient, some lesions disappeared, and normal skin appeared (diameter of 2 cm or less, especially in the lower limbs). Skin lesions were reduced to 25-30% in total. The itching recurred at about 1.5 weeks after the first injection of two doses, but did not reappear after the third and fourth injections, and arthritis did not occur. There were no side effects after the injection.

Example 2

A 50 - year - old man has been suffering from systemic psoriasis for 25 years. A rash appeared in the head and right upper quadrant and later spread in the torso and upper limb. The patient received treatment similar to that described in Example 1. He was also treated with ultraviolet light therapy, peloids, and hydrogenated sulfur baths, but the effect was not sustained. There was no comorbid disease except for asthenia, evisceration and left ventricular hypertrophy. Back, back, and shoulder skin were covered with combined lesions of erythematous vulgaris, vesiculopathy, and epidermal abscess. The rash on the lateral chest and lower extremities was mainly red and less marked. Skin lesions covered about 50% of the body surface. The patient did not complain of itching.

The patient underwent intravenous drip infusion of cardiac acid six times according to the following schedule.

On the first and second days, 500 mg of each of cardioxane,

1000 mg of cardioxane on days 15 and 16, respectively, and

On the 29th and 30th day, 1500 mg of each of cardioxane.

In the 15 and 29 day experiments, a slight improvement in erythema was noted in the patient's back. The remaining lesions were unchanged. Side effects did not appear.

Example 3

A 37 year old female patient had a history of 16 years after the onset of abortion and mental stress. The rash of psoriasis appeared in the part of the scalp of the neck and head and spread throughout the body. The patient sunbathed but only had a temporary effect. The patient had been admitted four times to be treated with vitamins, calcium and various ointments. After a period of intense stress caused by the death of a close person, the patient was rapidly worsened by the disease, and the erythematous lesions covered most of the body. The patient also had a history of allergic asthma bronchitis.

On the first day of the first experiment, the patient presented with persistent erythematous psoriasis rash with epidermal detachment, abdomen (below wrist), inguioileac, lumbar sacral and buttock area and lower limbs, severe itching Accompanied by a scraping organ (asthmatic bronchitis). Notably, there was a marked increase in the number of eosinophils.

Cardioxan was injected intravenously into the patient six times according to the protocol given in Example 2. On the 15th day of the experiment, the patient reported that the itching of the skin completely disappeared 2 or 3 days after the first injection of cardioxan. Less than half of the abdomen had practically no rash. There was no adverse effect except weak pain along the venous route at the injection site after the injection of cardiac acid.

On the 30th day of the experiment, the patient exhibited complete recovery of about 80% of the rash with residual pigmentation in the sac lumbar region and leg. Itching did not appear. Although the patient had allergic symptoms, no side effects were observed.

Example 4

The efficacy and tolerability of dexlazoic acid in patients with refractory psoriasis was evaluated in clinical studies.

After screening, appropriate patients were treated with Cardioxane daily for two consecutive days. 500 mg was administered by intravenous infusion. They were evaluated 7 and 14 days after the first day of treatment. Patients should be given 1000 mg of Cardioxane daily for two days (in this case, 15 and 16 days) if a complete response occurs, if there is an intravenous infusion or incomplete response of 500 mg of Cardioxane daily for two days (in this case, 15 and 16 days) And a second cycle of intravenous infusion.

After the same interval, they received treatment for the third cycle (in this case, 29 and 30 days). Patients with complete response received the same dose administered in the second cycle, and patients who did not respond had received 1500 mg twice.

The primary efficacy factor is the percentage reduction in skin area and severity affected by psoriasis, which was measured by standardized assessment of psoriasis area and severity index (PASI).

Seven patients were included in the study, and all patients completed a two - week period. At the start of treatment, the PASI score ranged from 23.1 to 44.1, with an average of 31.9. Most patients responded to treatment, but only one patient was totally resistant to treatment. At the completion of the third treatment cycle, the PASI score ranged from 3.4 to 29.7, with an average of 11.4.

After 11 weeks of treatment, the rate of reduction in PASI was up to 88%, with one case of resistance and an average of 65%. Treatment tolerance was excellent and serious side effects were not reported. In addition, treatment with Cardioxane resulted in a better and faster symptom relief associated with psoriatic arthritis compared to the treatment of Cyclosporin A (which has previously been used clinically as a standard treatment for this condition).

The results are shown in Table 1 and graphically in Fig.

[Table 1]

Effect of Cardioxan Therapy on Psoriasis Area and Severity Index (PASI)

PASI scores and patient numbers / initials

Number of visits 1 / HH 2 / MR 3 / MZ 4 / PH 5 / PZ 6 / FJ 7 / DJ v1 23.1 43.6 29.8 27.0 29.1 44.1 26.6 v4 11.3 36.3 18.4 18.6 16.9 24.8 23.6 v7 7.7 23.1 11.6 13.5 9.9 20.3 23.0 v9 6.5 15.6 9.7 10.8 9.3 15.6 21.8 v10 6.5 12.3 7.1 12.0 7.8 15.6 28.5 v11 5.6 14.0 6.5 5.2 3.4 15.3 29.7

Mean PASI score at baseline (n = 7):? = 31.9

Mean PASI scores at 7 weeks (n = 7):? = 11.4

The mean reduction rate (n = 7) in the PASI score was 65%

Of the seven patients treated, only one was diagnosed with weak recoverable leukopenia (approximately 3 x 10E9 cells per liter, class I) after the first week of treatment. After another week neutropenia disappeared and the count became normal. All other patients had normal white blood cell counts. Assessment of toxicity was in accordance with the WHO classification: grade 0 (non-toxic, baseline, number greater than 4 × 10E9), grade 1 (weak) to grade 4 (most severe). No cases of vomiting, nausea, or diarrhea were reported.

Most of the information so far indicates that the patient is still in a state of calm after one month of the last injection. Three patients were not cured, but the disease became a mild symptom that had not been treated well in the same way as conventional ointments. All patients had already suffered from psoriasis, which was previously untreatable for other therapies.

In a separate study of three patients with long-term intractable psoriasis, one patient still had relatively few lesions and symptoms one year later. This patient can be treated with a conventional emulsion as a patient suffering from miserable refractory psoriasis. Therefore, dexlazoic acid has the potential to relieve intractable psoriasis for a significantly longer period of time with low levels of side effects.

Example 5

The injection solution is prepared as follows:

Cardioxane? Is marketed as a 36 ml brown glass vial. Each vial contains 500 mg of the active ingredient of the lyophilized dexlauric acid hydrochloride. For reconstitution, the contents of each vial were dissolved in 25 ml of sterilized drinking water. The contents were dissolved in a few minutes under gentle stirring. The pH of the obtained solution is about pH 1.6.

For injection, the solution needs to be further diluted. For injection, sodium lactate UP (0.16M) or Ringer-Lactate BP is preferred. Both solutions provide an infusion solution with an acceptable pH.

Four vials of Cardioxane - diluted (reconstituted)

solution Capacity (ml) pH Total volume after dilution (ml) Sodium lactate UP (0.16M) 500 4.66 600 300 4.47 400 100 3.80 200 Ringer-Langate BP 500 3.45 600 400 3.19 500 300 2.85 400 100 2.14 200

Example 6

Tablets were prepared with the following composition:

mg / tablet

Cardioxane? 100 mg

Avicel? (Microcrystalline cellulose) 16 mg

Starch 9 mg

3 mg of hydroxypropyl methylcellulose

1 mg of magnesium stearate

0.6 mg of polyvinylpyrrolidone

0.3 mg of colloidal silicon dioxide

Half of the total amount of hydroxypropylmethylcellulose, polyvinylpyrrolidone and a sufficient amount of water were mixed with each other and stirred until dissolved (binder solution). Cardioxane, starch and the remaining amount of hydroxypropylmethylcellulose were mixed in a grader and stirred for 10 minutes. The granulation process begins by spraying the binder solution. After spraying and mixing, the product is dried in the same apparatus and taken out when the moisture content is 2.8-3.0% or less. The granules were passed through a vibrating granulator equipped with a 1.2 mm stainless steel screen. The starch, microcrystalline cellulose and colloidal silicon dioxide and particles were mixed for 20 minutes under rotation. Magnesium stearate was added and mixed with the granules. The final product was compressed to 130 mg in a rotary tablet unit equipped with a 10 mm diameter lens shaped punch.

Example 7

An ointment was prepared having the following composition:

g / 100 g ointment

Cardioxane? 1.5 g

10 g of liquid paraffin

15 g of polyoxyethylene-20-stearyl ether

Propylene glycol 5 g

White vaseline 40 g

Purified water 28.5 g

Cardioxane? Was reconstituted in cold water. The other components were melted at 60 DEG C and stirred. Cardioxane was added and the product was stirred until the tea was cold.

Example 8

A cream of the following composition was prepared:

g / 100 g cream

Cardioxane? 1 g

Glycerin monostearate (Tegin M?) 4 g

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

Cetyl stearyl alcohol 6 g

Viscous 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, cetylstearyl alcohol, paraffin and vaseline were heated to 60 DEG C and stirred. A small amount of water was boiled briefly, cooled to 60 ° C, and magnesium sulfate and glycerol were added and stirred. Cardioxane? Was reconstituted in the remaining negative water and added to the solution. Now, the two phases were emulsified in an emulgator and cooled to obtain a homogeneous cream.

Example 9

The gel was prepared with the following composition:

g / 100 g gel

Cardioxane? 1.2 g

20 g of isopropyl alcohol

100 g glycerol 2 g

1.8 g of hydroxyethylcellulose

Purified water 75 g

Half of the total amount of water and glycerol were heated to 50 캜; Hydroxyethylcellulose was added and stirred until a homogeneous gel was obtained. Cardioxane? Was reconstituted with the remaining water and added under constant speed stirring. The gel was cooled to 25 DEG C and the mixture was stirred under vacuum until isopropyl alcohol was added and a homogeneous gel was obtained.

Claims (31)

(3, 5-dioxopiperazin-1-yl) propane represented by the following formula in the preparation of a medicament for the treatment of psoriasis, or a physiologically acceptable salt thereof Uses: . The method according to claim 1, Wherein said physiologically acceptable salt is dexroxane HCl. 3. The method according to claim 1 or 2, Wherein said medicament is for injection or infusion. The method of claim 3, Wherein the medicament comprises a powder for reconstitution into a solution prior to injection. 3. The method according to claim 1 or 2, Wherein said medicament is in the form of epidermal, transdermal or dermal penetration. 6. The method of claim 5, Wherein the medicament is in the form of an ointment, lotion, or ointment. 3. The method according to claim 1 or 2, Wherein said medicament is in an oral form. 3. The method according to claim 1 or 2, Wherein said medicament is in the form of a suppository. The method according to claim 3 or 4, Wherein said medicament comprises about 250 mg to about 750 mg (e. G. 500 mg) of dextro-acid, calculated as dexlazanic acid hydrogen chloride in unit dosage form. The method according to claim 3 or 4, Wherein the medicament comprises about 750 mg to about 1250 mg (e.g., about 1000 mg) of dextro-acid, calculated as dexlazanic acid hydrogen chloride in unit dosage form. The method according to claim 3 or 4, Wherein said medicament comprises about 1250 mg to about 1750 mg (e.g., about 1500 mg) of dextro-acid, calculated as dexlazanic acid hydrogen chloride in unit dosage form. 12. The method of claim 11, Wherein the medicament is in the form of a topical dosage form wherein the dexlauric acid is present in the medicament in a concentration of from about 0.1% to about 5% by weight. 12. The method of claim 11, Wherein said medicament is applied to the skin, except for administration by oral, parenteral or injection or infusion. 3. The method according to claim 1 or 2, Wherein the medicament is an injectable or infusible formulation and is administered to an adult by a protocol comprising: (a) administering the medicament by injection or injection at a dose of about 250 mg to 750 mg, which is produced with dexlazan hydrogen chloride; (b) administering the medicament by injection or injection at a dose of about 750 mg to about 1250 mg, which is produced with dexlazan hydrochloride at a subsequent day; And (c) administering the medicament by injection or injection at a dose of about 1250 mg to about 1750 mg, which is produced with dexlazan hydrochloride at the subsequent day. Dexlazoic acid or a physiologically acceptable salt thereof, and a combination preparation for simultaneous, separate or sequential use for the treatment of psoriasis or an agent useful for alleviating the symptoms, for psoriasis treatment, especially a skin or parenteral formulation product. A therapeutically effective amount of a d-isomer of 1,2-bis (3,5-dioxopiperazin-1-yl) propane of the compound represented by the following formula in a therapeutically effective amount of dexrazoxane or a physiologically acceptable salt thereof: A method of treating psoriasis comprising: # 17. The method of claim 16, Wherein the dexlazoic acid is administered together with a physiologically acceptable diluent, carrier or excipient. 18. The method according to claim 16 or 17, Wherein the physiologically acceptable salt is dexlazonic acid HCl. 19. The method according to any one of claims 16 to 18, Wherein said dexlazoic acid is administered by injection or injection. 19. The method according to any one of claims 16 to 18, Wherein the dexlactic acid is administered epidermal, transdermal or transdermal. 21. The method of claim 20, Wherein the dexlazoic acid is in the form of an ointment, lotion, or ointment. 19. The method according to any one of claims 16 to 18, Wherein the dexlazoic acid is administered orally. 19. The method according to any one of claims 16 to 18, Wherein said dexlactic acid is in the form of a suppository. 24. The method according to any one of claims 16 to 23, Wherein the patient is an adult and wherein the method comprises administering an amount of about 250 mg to about 750 mg of dexlajic acid produced with dexlazan hydrochloride by injection or infusion. 25. The method according to any one of claims 16 to 24, Wherein the patient is an adult and wherein the method comprises administering an amount of about 750 mg to about 1250 mg of dexlactic acid produced with dexlazan hydrochloride by injection or infusion. 26. The method according to any one of claims 16 to 25, Wherein the patient is an adult and the method comprises administering an amount of about 1250 mg to about 1750 mg of dexlactic acid produced with dexlazan hydrochloride by injection or infusion. 24. The method according to any one of claims 16 to 23, Wherein the patient is an adult and the method (a) administering dexlajic acid by injection or injection at a dose of about 250 mg to about 750 mg, which is produced with dexlazan hydrogen chloride; (b) administering dexlajic acid by injection or injection at a dose of about 750 mg to about 1250 mg, which is produced with dexlazan hydrochloride at a subsequent day; And (c) administering dexlajic acid by injection or injection at a dose of about 1250 mg to about 1750 mg, which is produced with dexlazan hydrochloride at the following day ≪ / RTI > 17. The method of claim 16, Wherein the dexlazoic acid is administered to the skin. 29. The method of claim 28, Wherein dexlaa acid is administered in a topical formulation containing from about 1% to about 2% by weight dexlaa acid, calculated as dexlazanic acid hydrogen chloride. A method for the manufacture of a medicament for the treatment of psoriasis comprising the step of formulating dexlajosanoic acid or a physiologically acceptable salt thereof with a medicament for the treatment of psoriasis. 31. The method of claim 30, further comprising the features of one or more of claims 2-14.