Patent Application
20100189814
The present invention deals with an oral formulation for the treatment of sickle cell disease. The invention particularly deals with the treatment of patients with mild to moderate severity of symptoms and patients with sickle cell trait with a herbomineral composition.
Sickle cell disease is a genetic disorder which affects the red blood cells (RBCs). The RBCs of people with sickle cell disease contain a different form of hemoglobin called haemoglobin ‘S’. This is an abnormal type of hemoglobin and RBCs containing this hemoglobin become sickle shaped. They also become stiff and due to their distorted shape they have difficulty in passing through small blood vessels. When these sickle cells, thus block the blood vessels, less blood reaches that part of the body. Tissue that does not receive the normal blood flow eventually gets damaged. This is the main cause of the various complications including increased incidence of infections encountered in sickle cell disease.
The normal RBCs containing normal hemoglobin (called ‘Hemoglobin A’) not only are soft and round but also live up to about 120 days before new ones replace them. However, the RBCs from people suffering from sickle cell disease hardly have a life of about 10-20 days. The bone marrow can not make the new red blood cells fast enough to replace the dying ones. This results in severe anemia, which is one of the main symptoms of this disease. Sickle cell anemia affects millions of people worldwide.
Sickle cell disease is an inherited, life-long condition. People who have sickle cell anemia are born with it. They inherit two copies of the sickle gene from each parent. Sickle cell disease is prevalent world over including India. The major features of the sickle cell disease encountered in these patients include chronic fatigue, severe anemia, pain crises, bacterial infections, lung, liver and heart injury, leg ulcers, damage to the eye, inflammation of the hands and feet, arthritis, splenomegaly and chronic lung infections etc.
Sickle cell trait is an inherited condition in which both Hemoglobin A and Hemoglobin S are produced in Red Blood Cells, always more ‘A’ than ‘S’. people with Sickle cell trait may also develop some complications at a later stage in life. Under unusual circumstances serious morbidity and mortality can result from polymerization of de-oxy hemoglobin S; these complications include increased urinary tract infections in women, gross hematuria, complications of hyphema, splenic infarction with altitude hypoxia or exercise and life threatening complications of exercise, excertional heat illness or idiopathic sudden death. In addition, certain disease associations have been noted with sickle cell trait—such as early end stage renal failure, renal medullary carcinoma and polycystic kidney disease.
Though efforts have been made to control many of the symptoms and complications of the disease, the results are far from satisfactory in providing lasting cure and comfort to the sickle cell patient. Usually the health maintenance for these patients starts with early diagnosis, preferably in the newborn period and includes penicillin prophylaxis, vaccination against potential bacterial disease and folic acid supplementation. Treatment of complications often includes antibiotics, pain management, intravenous fluids and surgery all backed by psycho-social support. Blood transfusions help sickle cell disease patients by reducing recurrent pain crisis, risk of stroke and other complications. Because blood cells contain iron, and there is no natural way of eliminating excess iron, patients who receive repeated blood transfusions accumulate iron in the body till it reaches toxic levels.
A constant search is going on to find a substance which can stop sickling of RBCs or which can at least offer lasting symptomatic relief to a patient with sickle cell disease. One of the most promising drugs for this condition was Hydroxyurea, which is essentially an anti-cancer drug. Hydroxyurea has been shown to reduce the painful crises and acute chest syndrome in adults and to lessen the need for blood transfusions. Hydroxyurea seems t work by increasing the fetal hemoglobin in the RBCs. But being a potent anti-cancer drug, it has its own side effects. the major side effects of Hydroxyurea include decreased production of platelets, red blood cells and white blood cells. The effects of long term hydroxyurea is yet to be established.
Bone marrow transplantation is another procedure which is being tried in sickle cell disease, mainly in severely affected children. Though it may give dramatic results, its routine use is not possible because of the complications associated with the procedure besides the high cost and the need for highly sophisticated infrastructure and appropriate donors.
Efforts are being made to search for natural and herbal products which can offer therapeutic effect in sickle cell disease without producing undue adverse effects. Vanillin, a food additive, has been evaluated as a potential agent to treat sickle cell disease. Studies have indicated moderate antisickling activity when compared to other aldehydes. Abraham et al; PMID2001455.
A phytochemical formulation has been patented in US by National Institute for Pharmaceutical Research and Development Federal Ministry of Science and Technology (Ahuja, NG). the composition is a cold water extraction product of a mixture containing Piper guineenses seeds, Pterocarpus osum stem, Eugenia caryophyllum fruit, Sorghumbicolor leaves and potash. Though promising, more clinical studies are required before the safety, efficacy of t formulation could be established. (U.S. Pat. No. 5,800,819)
There is also a mention of hydration of sickle eryrocytes using a herbal extract (pfaffia paniculata) in vitro (British J. Haematology (2000); 111359-362)
Sickle cell disease is an international health problem and truly a global challenge. Hence efforts are being made to find out an ideal therapy which is effective and at the same time also safe. But so far none of the medications or procedures as described earlier have come anywhere close to what is desirable. Some compounds have been found to be safe but not
We referred to this formulation as T AYU HM PRE-300
A brief description of the ingredients used in the present formulation (T AYU HM Pre-300) are as follows;
It is found to be useful for anemia, splenomegaly, Aging and general debility. It is supposed to be also an energizer (Rasrana Sammucchay in Hindi (Part 1) Prof Dattatray Kulkarni).
The indications include Iron deficiency Anaemia, Leukemia'Bone marrow depression It is also known to strengthen muscle and nerve tissues. (Bhartiya Rasashastra in Gujarati by Vaidya Bapalal.)
The part commonly used is he fruit. Haritaki is an excellent drug for constipation. The clinical use include-infectious disease such as chronic ulcers, leucorroea, pyorrhea, and fungal infections of the skin. (CHEMEXIL-Selected Medicinal plants of India, 1992)
Parts used; Rhizomes. Ginger is known to have significant antiemetic and anti vertigo effects. The other main indications include Bronchial asthma, Rheumatic disorders, common cold and motion sickness. (Central Research Institute (AYUSH) Bhubaneshwar, “efficacy of Ginger’)
Parts used: Root and Leaves. It is used as a general tonic and aphrodisiac. Also found to be useful for acidity. (Satyavati, Pharmacology Review 1983, p-123).
Parts used: Roots. It is used for multiple clinical indications such as Diminished lactation, habitual abortion, Skin infections and as a stimulant, galactogogue, and tonic. (Medicinal Plant of India, ICMR, New Delhi, 1976, Part 1.)
Parts used: Fruit rand, roots, root bark, Flowers mainly used for Helminthiasis: Other indications include—reduced appetite, diarrhoea, Nausea, vomiting, Epistaxis (Hamdard XXVI; p-10 Antidiarrhoeal & antidysentric.)
Parts used: Roots, Stems, Leaves. Used in the compound formulation for treatment of Jaundice, Rheumatoid Arthritis, Gout, Diabetes and General Weakness. (Planta Medica 983, Vol. 48, p. 278; Indian journal of Pharmaceutical Sciences April-May 1985, p. 65)
Parts used: Root, Stem and Fruit. Used for the treatment of Malaria, bronchial asthma, and Hepatitis. Also gives good relief in dyspepsia and flatulence.
Parts used: Seed. Known to possess potent antibacterial 1, anti-inflammatory, anlgesic and anti-oxidant property besides having anticovulasant and hynotic effects. Also used as carminative, antiflatulent and tonic for heart and brain.
The unique combination of the above ingredients at individual concentrations as mentioned above arrived at after a lot of trials has demonstrated a potent and synergistic antisickling activity in vitro as well as in Vivo.
Blood samples were collected from the patients identified positive for sickle cell anemia. Antidrepanocytary activity of the test formulations were evaluated using Emmel's test.
With the followed test protocol the blood samples undergoes sickling in deoxygenated conditions induced by anaerobic conditions of Emmel's test protocol.
The test formulations showed significant inhibition of sickling of RBCs. The formulation of the present invention revealed 62.61+−1.44%, 66.28+−1.11%, 77.57+−1.19%, and 87.68 +−0.95% anti sickling activity at concentrations of 10 ug/ml, 25 ug/ml, 50 ug/ml, and 100 ug/ml respectively. (Table 3, 4; Graph 1, 2)
This novel herbomineral formulation of the present invention not only reduces painful episodes in the sickle cell patients and also protects the vital organs. The formulation has been found to be safe and well tolerated in all the patients.
Hence the present invention fills the void in the treatment of sickle cell disease and enhances quality of life of these patients.
In another embodiment, to the herbomineral ingredients described above ‘Kajjali’—which is made from equal portion of mercury and ‘gandhak’ is added. The preferred concentration of the Kajjali is approximately 50 mg. Addition of ‘Kajjali contributes to antisickling activity. Composition containing
Kajjali could be used along with other ingredients as described in Example 1, in cases where substances like Kajjali are tolerated by the patients even on long term use. The preferred composition of herbomineral ingredients containing Kajjali is as shown below:
A brief description of Kajjali is as follows:
When Sulphur (Ghandhaka) is added to Mercury (Parada) and triturated without adding liquid till it becomes a very fine black powder it is called Kajjali; Made from equal portion of Mercury and Gandhak. It is considered to be an Ayurvedic antibiotic or antibacterial medicine. (Rasatarangini, taranga2; 27) It is believed that the combination of these metals carry the actions of the herbs to the subtle channels and tissue of the body.
| Number | Date | Country | Kind |
|---|---|---|---|
| 1620/MUM/2007 | Sep 2007 | IN | national |
| 564/MUM/2008 | Mar 2008 | IN | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/IN08/00590 | 9/16/2008 | WO | 00 | 3/10/2010 |
