OA10789A - Phytodrug for treatment and menagement of sickle cell anaemia and method of preparing and using same - Google Patents

Description

TITLE QF THE INVENTION PHYTODRUG FOR TREAMENT AND MANAGEMENT OF SICKLE CELLANEMIA AND METHODS OF PREPARING AND USING SAME.

BACKGROUND OF THE INVENTION

Field of the Invention: * -

The présent invention relates to the field of Phytodrugs, and in particular the inventionrelates to Phytodrugs for treatment and management of Sickle Cell disease andmethods of preparing and using same.

Prior Activities and Problem in the Field

Y 5 Sickle Cell Disease (SCD) is a genetic disorder which, in particular, shows its clinicalmanifestations in the black race. At the présent time there is no known safe drug forthe management of this disease anywhere in the world. Nigeria, being the mostpopulous Black nation in the world, has the highest incidence of SCD.Conservatively, it is estimated that over 2 million Nigérians suffer from SCD while 10 another 25 million Nigérians are carriers. About 100,0000 babies are bom every yearwith SCD and it causes approximately 8% of ail infant deaths each year.

The morbidity and mortality factors associated with sickle cell disease are wellknown. The acute and chronic trauma of the painful crisis are beyond description. Inview of these realities, there is a constant need for drugs which might alleviate the 15 effects of this terrible disease. And the search for such drugs is of the highest priority.

The first known case of SCD involving a 20 year old West Indian student studying inAmerica was described by Herrick in 1910. However, centuries before Herrickdocumented this case, SCD was known to the people of West Africa. In fact,archaeological research in Nigeria has unearthed 700-year-old human bones showing 20 evidence of sickle cell infarcts. SCD is a hereditary disease of the red blood cells characterised by the presence of anabnormal gene that causes production of abnormal haemoglobin of the sickle or "S”variety. It is not known exactly when, how or where the mutation producing thesickle cell gene occurs, but the sickle cell gene is found to be prévalent in malaria 25 endemic régions of tropical Africa.

Painful épisodes are by far the most common complications of SCD. About 70% ofpatients with painful épisodes do not even seek professional medical assistance. Butone of the primary goals of management of painful épisodes is to alleviate pain andsuffering. 1 "J ü78â

SUMMARY OF THE INVENTION

It is a primary objective of the présent invention to provide a phytodrug that is usefulin the care and management of sickle cell disease in persons afflicted with suchdisease. It is also an objective of the invention to provide methods for prcparing auseful Phytodrug and for treating persons afflicted with sickle cell disease.

With the foregoing in mind, the présent invention provides a composition for treatingsickle cell disease comprising a cold water extraction product of a mixture containingPiper Quineenses seeds, Pterocarpus osun Stem, Eugenia caryophylîum fruit, andSorshum bicolor (Caudatum) leaves. The mixture may also include potash.

In its presently most preferred form, the mixture may include about 15.8 percent byweight of the said Piper Quineenses seeds, about 18.4 percent by weight of the saidPterocarpus Osun stem, about 13.2 percent by weight of the said Eugeniacarvophvllum fruit, about 31.6 percent by weight of the said Sorghum bicolor leaves,and about 21.0 percent by weight of Potash

In another aspect the invention provides a method for preparing a composition fortreating sickle cell disease. The method includes the steps of forming a mixturecontaining Piper guineenses seeds, Pterocarpus osun stem, Eugenia caryophylîumfruit, and Sorghum bicolor leaves and subjecting the said mixture to extraction usingcold water to thereby form an extract containing a drug material effective for treatingsaid sickle cell disease. The mixture may also include potash.

The invention also provides a method for treating a human afflicted with sickle cellcisease. In this aspect of the invention the method includes forming a mixturecontaining Piper guineenses seeds, Pterocarpus osun stem, Eugenia carvophvllumfruit, and Sorghum bicolor leaves, subjecting the said mixture to extraction using coldwater to thereby form an extract containing a drug material effective for treatingsickle cell disease, and treating a human afflicted with sickle cell disease with thedrug material. In this aspect of the invention, a dose of approximately 166.7 mg ofsaid drug material may be administered orally to a person afflicted with sickle celldisease.

Petailed Description Of Preferred Embodiments Of The Invention

In accordance with the invention, a composition for treating sickle cell disease isprovided- The composition consists of a cold water extraction product of a mixturecontaining Piper guineenses seeds, Pterocarpus osun stem, Eugenia caryophylîumfruit, anc Sorghum bicolor leaves. Preferably the initial mixture may also includepotash.

Phyiochemical screening indicates that the extraction product contains flavonoids.alkaloids. saponins, tannins, glycosides and traces of anthraquinones. However, theextraction product does not include steroids or fatty acids. In this regard, it ispostulatec that the major contributor to the anti-sickling properties of the drugmarerials of the invention may be the tannin content of the Eugenia caryophylîumfruit. Moreover. it is believed also that the other ingrédients of the extracted drug 2 01078: materials may hâve a synergistic effect which enhanees the bénéficiai effcct of thedrug materials overall when used in connection with the treatmcnt and management ofsickle cell disease.

In accordance with the preferred form of the invention, the initial mixture from which 5 the extraction product is prepared includes about 15.8 percent by weight of Piperguineenses seeds, about 18.4 percent by weight of Pterocarpus osun stem, about 13.2percent of weight of Eugenia caryophyllum fruit, about 31.6 percent by weight ofSorghum bicolor leaves, and about 21.0 percent by weight of potash.

The various raw materials described above are weighed, mixed together and then 10 subjected to cold water extraction for 24 hours. The fluid containing the extract isthen decanted and filtered and the residue is discarded. The filtrate is freeze-dried for48 hours using a Finn-Aqua Lyovac GT3 freeze dryer to provide a dry powdercontaining the active drug materials extracted from the initial mixture.

The powder containing the active drug materials may then be formulated into capsule 15 dosage form. Each capsule may preferably contain 166.7 mg of the freeze-driedpowder and inert additives in sufficient quantifies to provide a 300 mg per capsule.

It has been determined that the most effective daily dosage consists of four capsulesfor adults and two capsules for children. The daily dosages should be administered intwo divided doses with one-half of the daily dosage taken twice daily. Preferably the 20 separats divided doses will be taken in the moming and again in tire evening.

In accordance with the invention, it was initially observed that the extracted drugmaterials described above protected red blood cells obtained from sickle cell patientsagainst sickling when such cells obtained from sickle cell patients were exposed toIow oxygen tension. This effect lasted for over 48 hours while the protection was 25 about 91%. Furthermore, laboratory data clearly indicated the dose dépendantreversai of already sickled red blood cells using the described plant extracts. Thisreversai also lasted for over 48 hours and the effect was 100%. These tests indicatedthat the extract had scientific justification for possible bénéficiai effect in sickle cellpatients- Safety évaluation tests were therefore conducted. The data obtained from 5° such évaluation tests clearly show that the product is very safe. Carcinogenicity andmutagenicity évaluation were also conducted and the obtained results indicate that thedescribed drug materials are devoid of such adverse effects.

In accordance with the présent invention, the procedures and policies recommendedby WHO hâve been followed in developing and testing the efficacy of the drug 35 materials of the présent invention. Thus, the drug materials of the invention werestandardàsed and formulated into capsule dosage form as described above.

Clinical trial phase I was conducted using staff of the Nigérian National Institute forPharmaceutical Research and Development (NIPRD) as volunteers. The clinicalparameters of the blood chemistry, the liver functional status as well as kidneyfuDCtional status were assessed. It was thus determined that the drug materials of theinvention had no adverse effect on the volunteers regarding ail the parameters studied. 3 ί>10.7£;$ iniually dunng the phase IIA clinical trials, the staff of NIPRD went regularly to thehomes of patients so as to make vital observations with respect to the response of thepatients to the new drug materials of the invention. Later, due to the encouragingresults obtained, the visits were reduced to once a month. After one and half years,the patients were seen only about once every two months at clinics established byNIPRD. The clinical status of each patient was assessed by medical doctors at theseclinics.

Laboratory tests were conducted to evaluate the functional status of the liver, thekidney and the blood chemistry. Approximately 500 patients coming front differentparts of Nigeria were involved in the testing. Because of the large number of patientsinvolved, three clinics in ail were established by NIPRD to attend to patients involvedin the clinical trials.

From the data obtained it had been determined that the new drug materials of theinvention hâve no détectable adverse affect on the kidney, liver and the blood 15 chemistry. The values recorded for these parameters fall within normal range. On theaverage, about 90% of the patients involved in the clinical trials hâve not experiencedanv major sickle cell disease crisis since they entered the clinical trial program. Eventhe few patients (10%) who hâve experienced crisis reported that such crisis were lessfrequent and less severe as compared to their expériences before they joined the 20 clinical trial program.

The patients involved in the clinical trial program had improved appetitesaccompanied by appréciable weight gain. There was less incidence of anaemia andjatmdice, most likely due to the reduced rate of destruction of the red blood cells. It 25 was also observed that with patients involved in the clinical trial program whose testsindicated 60-90% sickling with sodium metabisulphite at the beginning of the study,such sickling tendencies had completely disappeared after about 8 months of using thedrug materials provided by the présent invention. These results are clearly highlyencouraging and probative of the efficacy of the drug materials of the invention. T- 'Γ*

Claims (7)

1. 010783 LU CLAIMS:

   1. A composition for treating sickle cell disease comprising a cold waterextraction product of a mixture containing from about 12 to about 17 parts byweight of Piper guineenses seeds, from about 15 to 19 parts by weight ofPterocarpus osun stem, from about 12 to about 18 parts by weight of Eugeniacarvophyllum fruit, and from about 25 to about 32 parts by weight of Sorghumbicolor leaves.
2. 2. A composition as set forth in claim 1, wherein said mixture comprises potash. A composition as set forth in claim 2, wherein said mixture comprises about15.8 percent by weight of said Piper guineenses seeds, about 18.4 percent byweight of said Pterocarpus osun stem, about 13.2 percent by weight of saidEugenia carvophyllum fruit, about 31.6 percent by weight of said Sorghumbicolor leaves, and about 21.0 percent by weight of said potash.
3. 4. A composition for preparing a drug effective for treating sickle cell diseasecomprising a mixture containing from about 12 to about 17 parts by weight ofPiper guineenses seeds, from about 15 to 19 parts by weight of Pterocarpusosun stem, from about 12 to about 18 parts by weight of Eugeniacarvophyllum fruit, and from about 25 to about 32 parts by weight of Sorghumbicolor leaves.
4. 5. A composition as set forth in claim 4, wherein said mixture comprises potash.
5. 6. A composition as set forth in claim 5, wherein said mixture comprises fromabout 12 to about 17 parts by weight of said Piper guineenses seeds, fromabout 15 to about 19 parts by weight of said Pterocarpus osun stem, fromabout 12 to about 18 parts by weight of said Eugenia caryophyllum fruit, fromabout 25 to about 32 parts by weight of said Sorghum bicolor leaves, and fromabout 15 to about 22 parts by weight of said potash.
6. 7. A composition as set forth in claim 6, wherein said mixture comprises about15.8 percent by weight of said Piper guineenses seeds, about 18.4 percent byweight of said Pterocarpus osun stem, about 13.2 percent by weight of saidEugenia caryophyllum fruit, about 31.6 percent by weight of said Sorghumbicolor leaves, and about 21.0 percent by weight of said potash.
7. 8. A method wherein a dose of approximately 116.7 mg of the said drug materialis administered orally to said person afflicted with sickle cell disease. 5