AU716895B2 - Formulation for iron chelation - Google Patents

Description

S F Ref: 359164

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT

ORIGINAL

Name and Address of Applicant: Actual Inventor(s): Address for Service: Invention Title: Council of Scientific Industrial Research Rafi Marg New Delhi-110001

INDIA

Sarkar Ajit Kumar, Kumar Sudarshan, Priyadarshi Harsh, Khanna Sushil Rattan and Dass Ghansham.

Spruson Ferguson, Patent Attorneys Level 33 St Martins Tower, 31 Market Street Sydney, New South Wales, 2000, Australia Formulation for Iron Chelation The following statement is a full description of this invention, including the best method of performing it known to me/us:- 5845 1 Formulation for Iron Chelation Field of the invention This invention relates to a formulation for iron-chelation and a process for preparing such formulation. The formulation of the present invention is useful for treating patients suffering from the disease of Thalassemia.

This invention relates particularly to a formulation useful for the treatment of patients suffering from the disease of Thalassemia with increased therapeutic efficacy.

Background of the invention Thalassemia Thalassemia is a dreaded disease among children because of genetic disorder. The disease is caused due to hereditary disorders connected with defective haemoglobin synthesis, characterised by hypochromia, microcytosis, haemolysis and a variable degree of anaemia. Thalassemia involves a heterogeneous group of molecular defects with a wide spectrum of clinical expressions.

Patients suffering from Thalassemia suffer from anaemia with decreased or absence of synthesis of globin chain of a normal haemoglobin. The patients of Thalassemia are broadly classified into two major groups according to the affected globin chain.

The patients suffering from alpha Thalassemia are associated with decreased or absence of a-chain synthesis. The patients suffering from beta Thalassemia are 20 associated with decreased or absence of P-chain synthesis.

One may find also patients suffering from Thalassemia delta and Gamma (y) chain disorders, as well as those associated abnormal haemoglobin structure (eg. Hb Lepose and Hb Constant Spring). These are rare and also contribute to the Thalassemia Syndromes.

25 The disease Thalassemia occurs world wide with a particular high incidence in the Mediterranean basin and in the South-East Asia. Malaria is also endemic in these areas, a significant fact since indirect evidence suggests that Thalassemia (major) heteroxygosity confers protection against malaria.

The P-Thalassemia or Thalassemia major type of the disease comprises a heterogeneous group of disorders usually characterised by absence of (P1) or decreased globin synthesis.

The type of P-Thalassemia is also classified according to the severity of the anaemia. These clinical classifications serve to differentiate homozygous (Thalassemia intermedia or Thalassemia major) from heterozygous state (Thalassemia minima or Thalassemia minor). Though, it does not reflect genetic mutation, Thalassemia (minor) is a reduced rate of P-globin synthesis, with an increased o(a-p-globin chains, but it is not life threatening.

Thalassemia (Major) also known as Cooley's anaemia, Mediterranean anaemia and Von Jacksch's anaemia is characterised by marked anaemia (ranging from 1 to 6g/dL of haemoglobin), severe haemolysis and ineffective erthropoiresis. The diagnosis is made in N:libc\O1689 the 1st year of the life of the patient, often as early as 3 months old baby. In the case of Thalassemia (Major), iron in the haemoglobin also breaks down and gets deposited in the vital organs of the body of the patients eg. liver, kidney, spleen, heart etc. This is also known as iron overloading in the body and the life span of the child suffering from s Thalassemia (major) becomes unpredictable. Every year out of 1 000 000 children born with Thalassemia (major) in the world, 10 000 are born in India.

Prior art treatments of thalassemia The method which is available hitherto for the treatment of Thalassemia (major} is life long blood transfusions coupled with the taking of the drug called 'Desferal' daily intermusculaly. The chemical name of the drug is deferoxamine methane sulfonate and the chemical formula is C2 8

H

52

N

4 0 1

S

Presently followed therapy is giving injection of Desferal for the excretion of iron from the body of the patient through urinary excretion. It was found by medical profession that Desferal had many side effects like swelling of limbs, stiffness in joints and may inhibit a number of tumour cell proliferation, parasite growth and the proliferation of the cerebral Malarial Parasite, Plasmodium falciparum.

In addition, the above drug is to be injected daily under the skin of the patient in a controlled manner in such a way to avoid any side reaction causing allergic conditions.

Such a treatment is highly painful. The treatment is also costly as the vial containing 500 mg of dry active substance will cost about US$10.00 each.

Though, a new oral iron chelating drug known as L-l, CP20, DMPH, Deferiprone (Chemical Name, 1,2-dimethyl 3 hydroxypyridine 4-one) has been reported very recently, it is yet to establish its potentiality of patients suffering from the disease of Thalassemia.

S 25 The reported side effects of this drug are 1. Myelotoxicity ie. occurrence of neutropenia 2. Orthropathy ie. skeleto-muscular pain and swelling around knee and hip joints and lastly mild zinc deficiency occasionally leading to dermatopathy (Reference may be made to the Proceedings of National Thalassemia Conference, 5-6 February, 1994, held in Delhi; LI: Oral Iron chelation Therapy-Indian Study by M.B. Agarwal). The cost of a capsule Deferiprone is approximately 50 US cents A patient has to take 3-6 capsules per day. This will amount to US$70-90 (Rs. 1000-2000) per month.

Another method which is available for the treatment of the disease Thalassemia (major) is by the bone marrow transplantation (BMT). This is done by the taking the bone marrow of the matching donor and injecting it to the patient. The cost of such a treatment is around US $50000.00(Rs.15,00,000/-). This is therefore beyond the reach of common man. Several treatments using bone marrow have been performed in many parts of the world including the USA and Italy. Recently, Christian Medical College (Vellore), India and Appolo Hospital (Madras) India have also started this type of BMT treatment in India, but the cost is also on the higher side (Rs.7 Lac. approx). Further, an increase in the life span expectancy of these patients has yet to be established.

N:libc\O 1589 Under the prevailing present day conditions, regular blood transfusion and use of the drug 'Desferal' by injection as explained above, is the best way to treat this dreaded disease. For the last one decade, efforts are being made by medical profession throughout the world to find a treatment of this disease by a drug which will be low in cost and can be administered orally and have no side effects, but so far there has been no success.

Objects of the invention Therefore, the main objective of the present invention is to provide a formulation useful for iron-chelation for the treatment of Thalassemrnia.

Another objective of the present invention is to provide a formulation useful for the treatment of Thalassemia with increased therapeutic efficacy.

Yet another objective of the present invention is to provide a formulation for the treatment of Thalassemia which is much cheaper and hence, affordable by a common man.

Still, another objective of the present invention is to provide a formulation useful for the treatment of patients suffering from Thalassemia which can be administered orally.

sdeA further objective of the present invention is to provide a formulation which has no side effects and is very convenient to administer.

Another object of the present invention is to provide a formulation useful for the treatment of Thalassemia, the dose of which can be continued for a long period without damaging any vital organs of the body of the patients.

Detailed description of the invention With the above objectives in view, our work initially was directed to red blood cells and at the same time, to enhance the oxygen carrying capacity to the tissues. Different compounds of vanadium, arsenic, oxalic acid and citric acid were tried initially but these compounds failed in making a major break through.

It has been observed that patients suffering from Thalassemic disease have a change in complexion, anorexia, blackness of gums, increase in serum ferretin level and a remarkable iron overload in the body due to the breaking down of red blood cells. The treatment mentioned above which involves repeated blood transfusion also accumulates the above elements in the body of the patients suffering from Thalassemic disease.

Children suffering from Thalassemia disease do not show any resistance from viral infection and also suffer from body aches. They are also immune to malaria.

Our research work was primarily directed to find an immediate solution for the survival of such patients, who had an iron overload in the body and the other side ailments mentioned above.

Efforts, therefore, were directed towards in finding out an alternate drug which can be used orally and have no side effects. Anemonin Pretensis (powder) has been used for many years by the tribal people of Siberia to poison their arrows. Anemonin Pretensis is extracted with an organic solvent such as ethanol from fresh whole wind flower plant (the botanical name by Anemonin) with roots and flowers and some fruits of wind flowers.

N:libc\O 15 689 The dried material is treated with an organic solvent such as ethanol and refluxed.

Anemonin Pretensis obtained from the extraction is filtered and recrystallised from an organic solvent such as ethanol. The medical history of this herb also reveals that this herb was involved in homeopathic practice in 1805 for some female hormone problem.

Anemonin pretensis has the formula.

HO OH The iron-anemonin complex has the structure.

a. a a a.

The iron-anemonin complex (stretched) has the structure Anemonin Pretensis is a pure herbal product. It is present in the wind flower plant which grows in the wild state in the open fields and plains in many parts of Europe, Russia and Turkey in Asia. The chemical formula of Anemonin pretensis having the formula shown above, isolated from fresh wind flower plant is 1-2-dihydroxy-l-2 cyclobutane-diacrylic acid di-lactone. Reference may be made to Merck Index P-87, Entry no. 677, 9th edition.

Patients suffering from Thalassemic disease are immune to malaria attack.

Considering the nature and considering that quinine sulphate is a known antimalarial drug which has antipyretic and analgesic properties, we considered incorporating quinine N:libc\O1589 sulphate in the formulation to reduce the high temperature and body-ache problem of the patients suffering from Thalassemic disease.

Quinine has the chemical composition C 20

H

2 4 N202. It is obtained from Cinchona bark available in India, Sri Lanka, Equador, Colombia, Peru and Bolivia. Cinchona thrives at higher elevations such as 1800 to 2500m. Quinine is also extracted with a solvent from the bark of the plant (Cinchona), refluxed, filtered and recrystallised with a solvent. The solvent can be water or any organic solvent such as ethanol. Quinine sulfate is prepared by reacting quinine and dilute sulphuric acid in a molar ratio as shown below: 2 C 20

H

24 0 2

N

2

H

2

SO

4

C

40

H

50 s0N 4

S

Quinine sulfate is a snow white, light, odourless and extremely bitter crystallised needles having the chemical composition C 4 0

H

48

N

4 0 4

H

2

SO

4 H0O. Reference may be made to Merck Index p-1049, entry no. 7879, 9th edition.

By our continuous and sustained research work based on the above mentioned directions, we observed that when we blended (preferable mechanically) the powder of Anemonin Pretensis with quinine sulfate and dissolved in suitable solvent and the solution was administered orally to the patient suffering from Thalassemia, there was remarkable improvement of complexion and reduction of serum ferritin level. There was no fever.

There was also no body ache. The treatment was continued and more patients were put on trial on this drug. There were no side effects. This revealed that the formulation is very Suseful in the treatment of the patients suffering from Thalassemia.

Accordingly, the present invention provides a pharmaceutical formulation useful for treating patients suffering from Thalassemia which comprises: i. Powder of Anemonin pretensis in an amount in the range of 0.02 to 0.12wt% of the formulation.

ii. Quinine sulfate in an amount in the range of 0.0005 to 0.003wt% of the formulation.

iii. Distilled or demineralised water in an amount in the range of 0 to 40wt% of the formulation, and iv. Edible solvent 99.88 to 60wt% of the formulation.

The preferred aspect of the invention provides a pharmaceutical formulation useful for treating patients suffering from Thalassemia which comprises: a. powder of Anemonin pretensis in an amount of 0.08wt% of the formulation, b. quinine sulfate in an amount 0.001wt% of the formulation, c. water in an amount of 40wt%, and d. ethanol is an amount of 59.919wt% of the formulation.

A more preferred aspect of the invention provides a pharmaceutical formulation useful for treating patients suffering from Thalassemia which comprises: a. powder of Anemonin pretensis in an amount of 0.09wt% of the formulation, b. quinine sulfate in an amount 0.001wt% of the formulation, c. water in an amount 80wt% of the formulation, and d. edible solvent in an amount of 19.909wt% of the formulation.

N:libc\O 189 6 The present invention also provides a process for the preparation of a pharmaceutical composition for treating patients suffering from Thalassemia, said process comprising mixing: a. Powder of Anemonin pretensis in an amount in the range of 0.02 to 0.12wt% of the formulation, b. Quinine sulfate in an amount in the range of 0.0005 to 0.003wt% of the formulation, c. Distilled or demineralised water in an amount in the range of 0 to 40wt% of the formulation, and d. Edible solvent in an amount in the range of 99.8 to 60wt% of the formulation.

The solvent used may be selected from water, ethanol, absolute alcohol etc. or mixtures thereof. The solvent may be present in an amount of 8 9.9795wt%, 89 .9592wt%, 89.939wt%, 89.918wt%, 89.97wt%, 89.95wt%, 88.87wt%, 89.92wt%, 89.94wt%, 19.909wt% and 59.919wt%.

The Anemonin pretensis powder and the quinine sulfate employed in the formulation may be of pharmaceutical grade.

The Anemonin pretensis possesses the properties of chelating iron. Quinine sulfate seems to accelerate the chelation of iron present in the body of the patient suffering from thalassemia. We have found by forming a formulation of Anemonin pretensis and quinine sulfate in the amount mentioned above results in an unexpected properties which are not present in the individual components. There is, therefore, a synergistic activity when they are combined in the above mentioned quantities.

The formulation of the present invention is therefore, not a mere admixture of the ingredients employed but a synergistic mixture, the properties of which are not merely the S 25 aggregate properties of the individual ingredients of the formulation.

Therefore, the present invention also includes a method of increasing the excretion of iron in a patient afflicted with Thalassemia comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition which comprises: a. Powder of Anemonin pretensis in an amount in the range of 0.02 to 0.12wt% of the formulation, b. Quinine sulfate in an amount in the range of 0.0005 to 0.003wt% of the formulation.

c. Distilled or demineralised water in an amount in the range of 0 to 40wt% of the formulation and d. Edible solvent in an amount in the range of 99.88 to 60wt% of the formulation.

The formulation of the present invention when administered to patients suffering from Thalassemic disease works as follows: N:libc\01689 The iron present in the body of the patients forms a complex with anemonin of Fe *Fe 0 0 0 \oo 0 0 F Fe formula or formula where three molecules of anemonin can form a complex with two iron atoms. The quinine sulfate present in the formulation acts as a catalyst for the formation of the complex thereby not 5 only reducing the amount of Anemonin in the complex/composition but also using the maximum amount of iron present in the body. In addition, the antipyretic and analgesic properties of quinine sulfate help to control the fever and the body ache problem present in such patients.

The iron complex is formed in the body fluids. The fluid containing the complex reaches the kidney through the body system and it is then excreted from the body of patients through urine. Some of the complex is also excreted through alimentary canal and finally faeces. By these processes the excess iron present in the body of the patients is removed thereby enhancing the life span of the patients. The various ingredients of the present formulation can be blended by any conventional methods such as mechanically 15 mixing etc.

The following examples are given by way of illustration and these should not be S"construed to limit the scope of the present invention.

Example 1 A formulation was prepared by blending the following ingredients: Powder of Anemonin pretensis 0.02wt% of the formulation Quinine sulfate 0.0005wt% of the formulation Demineralised water 10wt% of the formulation Ethanol solvent 89.9795wt% of the formulation Example 2 A formulation was prepared by blending the following ingredients: Powder of Anemonin pretensis 0.04wt% of the formulation Quinine sulfate 0.0008wt% of the formulation Demineralised water 10wt% of the formulation Ethanol solvent 89.9592wt% of the formulation N:libc\01589 Example 3 A formulation was prepared by blending the following ingredients: Powder of Anemonin pretensis 0.06wt% of the formulation Quinine sulfate 0.001wt% of the formulation Demineralised water 10wt% of the formulation Ethanol solvent 89.939wt% of the formulation Example 4 A formulation was prepared by blending the following ingredients: Powder of Anemonin pretensis 0.08wt% of the formulation Quinine sulfate 0.002wt% of the formulation Demineralised water 10wt% of the formulation Ethanol solvent 89.918wt% of the formulation Example A formulation was prepared by blending the following ingredients: Powder of Anemonin pretensis 0.09wt% of the formulation Quinine sulfate 0.001wt% of the formulation Demineralised water 10wt% of the formulation Ethanol solvent 89.919wt% of the formulation Example 6 A formulation was prepared by blending the following ingredients: Powder of Anemonin pretensis 0.12wt% of the formulation Quinine sulfate 0.003wt% of the formulation Demineralised water 10wt% of the formulation Ethanol solvent 88.8779wt% of the formulation Example 7 A formulation was prepared by blending the following ingredients: Powder of Anemonin pretensis 0.09wt% of the formulation Quinine sulfate 0.001wt% of the formulation Demineralised water 80wt% of the formulation Ethanol solvent 19.909wt% of the formulation Example 8 A formulation was prepared by blending the following ingredients: Powder of Anemonin pretensis 0.08wt% of the formulation Quinine sulfate 0.001wt% of the formulation Demineralised water 40wt% of the formulation Ethanol solvent 59.919wt% of the formulation The formulations mentioned in Examples 1 to 8 were administered to patients of different age groups who were suffering from Thalassemia. The patients were administered the above formulation orally after mixing it with water. The formulation was administered to the patient daily. Such a treatment was continued for a period of two months. All the formulations showed that iron is excreted through urine after the administration of the formulation at a range from 10-95%. This result points out that the formulation of the present invention is very effective for the chelation of iron, thereby reducing the serum ferritin level in the patients suffering from Thalassemia. Such a N:libc\O 1689 position results in longer and larger survival rate of the patients suffering from Thalassemia. The above mentioned results are shown in Table 1.

Table 1 Efficiency of the Formulation No. of used patient treated Example 1 3 Example 2 3 Example 3 3 formulation of the present invention.

Age Sex Frequency of Duration of (yrs) transfusion treatment (days) (months) 5 M 22 2 Example 4 Medicine Administered in drops twice daily 15 15 15 15 15 15 15 15 Excretion chelated iron 91 Example 5 3 Example 6 3 Example 7 3 Example 8 Table- 2 Comparison of Desferal, Deferiprone and the formulation of the present invention Name of medicine Desferal the Mode Administratic Injection (highly painfi Oral the Oral >n of Side effects Taste Adverse side effects such as a. ocular toxicity b. auditory meaurotoxicity c. cerebral toxicity d. allergic skin reaction e. cardiovascular and gastro-intestinal disturbances f. change in blood pressure More side effects than Desferal such as a.

Myelotoxicity b. Arthropathy c. Mild Zinc deficiency d. Questionable occurrence of immunological complications No side effects Does not apply Bitter taste Tasteless Deferiprone Formulation of present inventio From the above Table 2, it is clear that the formulation of the present invention is easy to administer because it is tasteless, colourless and odourless with no side effects even when administered for longer duration.

N:libc\ 01689 Table 3 Annual cost of treatment of Thalassemia using the hitherto know drugs and the formulation of the present invention.

Name of medicine Amount in US$ Reference Desferal 3000-6000 Iron Chelation Therapy C. Hershko D.J. Weatherall CRC Critical Reviews Clinical Laboratory Series 26(4), 314, 1988 Deferiprone(L-l) 800- 1100 News Review, United Kingdom Thalassemia Soc. Issue No.

61, March, Present formulation 50- 60 Table 3 illustrates that the cost of the present formulation is the cheapest when compared with known drugs.

The formulation of the present invention can be in the form of tablets, powder or suspension. However, the capsules containing the present formulation are the most preferred since it is easier to persuade to the patients to take them orally.

The main advantages of the formulation of the present invention are 1. Iron-chelation using the formulation of Anemonin Pretensis and Quinine sulphate is up to 2. The cost of the formulation is around US$5 to 10 (Rs. 150-200/-) per vial and it can be used for one month. The cost is much lower as compared to other currently available medicines in the market for the treatment of Thalassemia.

:15 3. The formulation has no toxic effects even when it is administered for longer period.

4. The formulation is tasteless and odourless and can be administered orally.

N:libc\O1689

Claims (8)

1. A pharmaceutical formulation which comprises a. Powder of Anemonin pretensis in an amount in the range of 0.02 to 0.12wt% of the formulation, s b. Quinine sulfate in an amount in the range of 0.0005 to 0.003wt% of the formulation, c. Distilled or demineralised water in an amount in the range of 0 to 40wt% of the formulation and d. Edible solvent in an amount in the range of 99.88 to 60wt% of the o1 formulation.

2. A pharmaceutical formulation as claimed in claim 1, wherein the Aneinonin pretensis present in an amount selected from the group consisting of 0.04wt%, 0.06wt%, 0.08wt% and 0.09wt% of the formulation.

3. A pharmaceutical formulation as claimed in claim 1 or claim 2, wherein the 15 Anemonin pretensis used is of pharmaceutical grade.

4. A pharmaceutical formulation as claimed in any one of claims 1 to 3, wherein the quinine sulphate used is of pharmaceutical grade.

5. A pharmaceutical formulation as claimed in any one of claims 1 to 4, wherein the quinine sulfate is present in an amount selected from the group consisting of 0.0008wt%, 0.001wt%, and 0.002wt% of the formulation.

6. A pharmaceutical formulation as claimed in any one of claims 1 to 5, wherein, the solvent used is water, ethanol or absolute alcohol.

7. A pharmaceutical formulation as claimed in any one of claims 1 to 6, wherein: the solvent is present in an amount which is selected from the group consisting of 25 89.9795wt%, 89.9592wt%, 89.939wt%, 89.918wt%, 89.919wt%, 89.97wt%,

89.95wt%, 88.87wt%, 89.92wt%, and 89.94wt% of the formulation. 8. A pharmaceutical formulation as claimed in any one of claims 1 to 7, wherein the formulation is in the form of tablets, powder, suspension or capsules. 9. A pharmaceutical formulation which comprises: a. Powder of Anemonin pretensis in an amount of 0.08wt% of the formulation. b. Quinine sulfate in an amount 0.001wt% of the formulation, c. Water in an amount of 40wt%, and d. Ethanol is an amount of 59.919wt% of the formulation. A pharmaceutical formulation which comprises: a. Powder of Anemonin pretensis in an amount of 0.09wt% of the formulation, b. Quinine sulfate in an amount 0.001wt% of the formulation, c. Water in an amount 80wt% of the formulation, and d. Edible solvent in an amount of 19.909wt% of the formulation. 11. A pharmaceutical formulation, substantially as hereinbefore described with reference to any one of the examples. N:Iibc\01689 12. A process for the preparation of a pharmaceutical composition, said process comprising mixing: a. Powder of Anemonin pretensis in an amount in the range of 0.02 to 0.12wt% of the formulation, b. Quinine sulfate in an amount in the range of 0.0005 to 0.003wt% of the formulation, c. Distilled or demineralised water in an amount in the range of 0 to 40wt% of the formulation, and d. Edible solvent in an amount in the range of 99.8 to 60wt% of the formulation. 13. A process as claimed in claim 12, wherein the Anemonin pretensis powder and the quinine sulfate used are of pharmaceutical grade. 14. A process for the preparation of a pharmaceutical composition, substantially as hereinbefore described with reference to any one of the examples. A method of increasing the excretion of iron in a patient afflicted with o 15 Thalassemia comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition as claimed in any one of claims 1 to 11. 16. A method of increasing the excretion of iron in a patient afflicted with Thalassemia comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition which comprises: 20 a. Powder of Anemonin pretensis in an amount in the range of 0.02 to 0.12wt% of the formulation, b. Quinine sulfate in an amount in the range of 0.0005 to 0.003wt% of the formulation. c. Distilled or demineralised water in an amount in the range of 0 to 40wt% of 9** the formulation, and d. Edible solvent in an amount in the range of 99.88 to 60wt% of the formulation. S17. Use of a. Powder of Anemonin pretensis in an amount in the range of 0.02 to 0.12wt%, b. Quinine sulfate in an amount in the range of 0.0005 to 0.003wt%, c. Distilled or demineralised water in an amount in the range of 0 to 40wt% and d. Edible solvent in an amount in the range of 99.88 to for the manufacture of a medicament for increasing the excretion of iron in a patient afflicted with Thalassemia, wherein the amounts in wt% are based on the total weight of said medicament. 18. Use according to claim 17 wherein the Anemonin pretensis is present in said medicament in an amount selected from the group consisting of 0.04wt%, 0.06wt%, 0.08wt% and 0.09wt% of the medicament. A 19. Use according to claim 17 or 18, wherein the Anemonin pretensis used is of rmaceutical grade. N:libc\O1589 Use according to any one of claims 17 to 19, wherein the quinine sulphate used is of pharmaceutical grade. 21. Use according to any one of claims 17 to 20, wherein the quinine sulfate is present in said medicament in an amount selected from the group consisting of 0.0008wt%, 0.001wt%, and 0.002wt% of the medicament. 22. Use according to any one of claims 17 to 21, wherein said solvent is selected from water, ethanol and absolute alcohol. 23. Use according to any one of claims 17 to 22, wherein said solvent is present in an amount which is selected from the group consisting of 89.9795wt%, 89.9592wt%, 89.939wt%, 89.918wt%, 89.919wt%, 89.97wt%, 89.95wt%, 88.87wt%, 89.92wt%, and 89.94wt% of the medicament. 24. Use according to any one of claims 17 to 23, wherein said medicament is in the form of tablets, powder, suspension or capsules. Use of 15 a. Powder of Anemonin pretensis in an amount of 0.08wt%, Quinine sulfate in an amount 0.001wt%, c. Water in an amount of 40wt%, and d. Ethanol is an amount of 59.919wt% for the manufacture of a medicament for increasing the excretion of iron in a patient 20 afflicted with Thalassemia, wherein the amounts in wt% are based on the total weight of said medicament. 26. Use of: a. Powder of Anemonin pretensis in an amount of 0.09wt%, b. Quinine sulfate in an amount 0.001wt%, c. Water in an amount 80wt%, and d. Edible solvent in an amount of 19.909wt% for the manufacture of a medicament for increasing the excretion of iron in a patient afflicted with Thalassemia, wherein the amounts in wt% are based on the total weight of said medicament. 27. A pharmaceutical composition according to any one of claims 1 to 11, when used for increasing the excretion of iron in a patient afflicted with Thalassemia. Dated 19 April 1999 Council of Scientific Industrial Research Patent Attorneys for Applicant/Nominated Person SPRUSON FERGUSON N:libc\O1589