FORM2

THE PATENTS ACT, 1970
(39 OF 1970) & THE PATENTS RULES, 2003 PROVISIONAL/COMPLETE SPECIFICATION (See section 10 and rule 13)

1. TITLE OF THE INVENTION: A HERBAL FORMULATION FOR TREATING
SICKLE CELL DISEASE
2. APPLICANTS)
(a) Name: DR.ATUL M. DESAI
(b) Nationality: INDIAN
Address: DHANVANTARI CLINIC
AYURVEDIC HEALTH CARE CENTRE SHREEJI DESAI MARKET, OLD BUS
(c) DRATUL M. DESAI INDIAN STAND, VYARA -
394650 GUJARAT

3.

COMPLETE

The following specification describes the Invention.
The following specification particularly describes the invention and the manner in which it is to be performed
4. DESCRIPTION (Description shall start from nest page)
5. CLAIMS (not applicable for provisional specification. Claims should start with the preamble —"I/We claim" on separate page)


6. DATE AND SIGNATURE (to be given at the end of last page of specification)

ABSTRACT OF THE INVENTION (to be given along with complete specification on separate
page)
2008
MUM.
1962

A HERBAL FORMULATION FOR TREATING SICKLE CELL DISEASE.
FIELD OF INVENTION:
The present invention deals with the treatment of sickle cell disease with an oral formulation of multiple herbal ingredients which is particularly useful even in pediatric population because of its safety. BACKGROUND OF THE INVENTION:
Sickle cell disease (anemia) is an inherited blood disorder which is particularly serious for infants and children. All complications of the disease can be traced to changes in the make up of the red blood cells. The RBCs in sickle cell disease contain a different form of hemoglobin called hemoglobin 'S'. This is an abnormal type of hemoglobin and the 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.
The young child with sickle cell anemia has special needs. If these needs are understood by those caring for the child, then complications can be prevented or treated early. The complications of this disease could be serious and sometimes fatal. The complications of sickle cell disease include: infections such as pneumonia, meningitis, kidney infections, bone infections, gall stone, damage to the retina, hip and should joint damage, stroke etc. Complications that can be fatal include: septicemia and acute splenic sequestration ie sudden enlargement of spleen and rapid drop in blood count Both of these medical emergencies can occur suddenly. Severe pain which may remain for hours or may continue for days is one of the worst symptoms of sickle cell disease which may necessitate treatment with stronger medications.
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 patient 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 anticancer 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 to 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 productioin 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 th complications associated with the procedure besides the high cost and the need for highly sophisticated infrastructure and appropriate donors.
Recently a phytochemical formulation has been patented in US by National Institute for Pharmaceutical Research and Development Federal Ministry of Science and Technology (Abuja, NG). The composition is a cold water extraction product of a mixture containing Piper guineenses seeds, Pterocarpus osum stem, Eugenia caryophyllum fruit, Sorghum bicolor leaves and potash. Though promising, more clinical studies are require before the safety, efficacy of the formulation could be established.

SUMMARY
The primary objective of the present invention is to provide a therapy for sickle cell disease ,a genetic and serious disorder for which hardly any feasible therapy is available except blood transfusion and secondary drugs like pain killers and antibiotics. Another objective of invention is to provide an effective therapy with least side effects in patients afflicted with sickle cell disease including paediatric patients. Yet another objective of the present invention is provide a cost effective therapy considering the chronic nature of the disease and the need for long term therapy. The invention provides a composition for the treatment of sickle cell disease comprising of only herbal ingredients such as Aloe vera,Amalki,Chitrak Jaiphal, Sunthi, jivanthi ,Haritaki„Guduchi, Shatavari, Dadima, Pippali, ;The composition to be preferably given by oral route for both adults and children suffering from Sickle cell disease.
DETAILED DESCRIPTION OF THE INVENTION:
The present invention describes a novel herbo-mineral formulation for treating the sickle cell disease. The main ingredients of the formulation and the preferred concentrations of the individual ingredients are as follows :

TABLE 1

INGREDIENTS Preferred Concentrations
.Aloe vera 50mg.
Amlaki [ Phyllanths emblica ] 50 mg.
Jaiiphal [Myristica fragrans houtt] 12.5mg
Sunthi [Zingiber Officinal Roscoe] 25mg
Jivanti Ghana [Leptadenia reticulate ] 12.5mg.
Haritaki Ghana [Term in alia Chebula ] 25mg.
Guduchi Ghana [Tinospora cordifolia] 12.5mg
Shatavari Ghana [Asparugus racemosus] 25mg.
Dadima [Punica granatum.Linn 12.5mg
Pippali [Piper longum linn] 25mg.
Chitrak [Plumbago zeylanica] 12.5mg
A brief description of the ingredients used are as follows;
ALOE VERA:
Parts used -Leaves juice and pulp .The plant and its parts are used for multiple indications. Indications include cough, cold, general weakness, asthma, viral hepatitis and diabetes.(Medicinal plants of India, Vol.1,ICMR 1976)
AMLAKI : (Phyllanths emblica)
Parts used ;Fruit, nut ,seed, leaves bark and flowers, mainly ripe fruits .
Multiple uses ;As a tonic , and in constipation, dyspepsia ,general weakness, hepatitis,

bronchitis, urinary tract infections etc
CHITRAK:fPlumbago zevlanica );
Pats used :Root ;root bark, seeds, The root is said to promote appetite and enhance
digestion. ;and also useful in piles, diarrhea ,skin diseases, and enlarged
spleen.
HARITAKI Terminalia chebuta ):
The part commonly used is he fruit. Haritaki is an excellent drug for constipation. The
clinical use include-infectious disease such as chronic ulcers ,leucorrhoea, pyorrhea, and
fungal infections of the skin.(CHEMEXIL-Selected Medicinal plants of India,1992 )
SHUNTHI: (Ginger offcianle):
Parts used ;Rhizomes. Ginger is known to have significant anti emetic 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')
SHATAVARI: (Asparagus racemosus):
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).
JIVANTI (Leptadenia reticulate W):
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,Partl.)
DADIMA: ( Punica granatum Linn)

Parts used: Fruit rand ,roots , root bark, Flowers .mainly used for Helminthiasis :Other
indications include - reduced appetite, diarrhoea, Nausea, vomiting, Epistaxis (Hamdard
XXVI; p-l0Antidiarrhoeal & antidysentric.)
GUDUCHI ( Tinospora cordifolia)
Parts used: Roots, Stems, Leaves .Used in the compound formulation for treatment of
Jaundice ,Rheumatoid Arthritis, Gout, Diabetes and General Weakness.( Planta Medica
1983,Vol.48,p.278; Indian journal of Pharmaceutical Sciences April-May 1985, p.65)
PIPPALI (Piper longum Linn
Parts used : Root, Stem and Fruit .Used for the treatment of Malaria, bronchial asthma,
and Hepatitis .Also gives good relief in dyspepsia and flatulence.
JAIPHAL (Myristica fragrans houtt
Parts used: Seed. Known to possess potent antibacterial ,anti-inflammatory, analgesic and
anti-oxidant property besides having anticovulasant an 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 and experimentations has demonstrated a potent antisickling activity in vitro as well as in vivo.
IN-VITRO TESTING FOR ANTI_SICKLING ACTIVITY:
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.

Emmet's test protocol:
A. For control group 20micro.L. of blood sample was treated with 20micro.L of
physiologic solution (0.9% NaCl solution) to maintain the osmotic condition of
the cellular medium and avoid precocious hemolysis of red blood cells.
B. For treatment group 20 micro.L. of blood sample was incubated with 20micro.L
of the polyherbal formulation containing 15 mg/ml, 30 mg/ml and 45 mg/ml
cicentrations of polyherbal formulation respectively.
→ A drop of A/B was put on slide and hermetically covered by cover glass using
vacuum grease. → In order to ensure complete anaerobic conditions the slides were placed in
vacuum desiccator and then transferred to incubator (37 C) for 24 hours. After 24 hours in anaerobic condition, RBCs undergo deoxygenation and adopt sickle shape due to polymerization and precipitation of Hemoglobin S. → The slides were observed for the presence of sickle cells count using Photo
microscopy with magnification at 45X digitalization of images with DTV250
software and recording with DIVIX software for the count of the number of sickle
cells present.
Blood samples from six patients(Age Range 12-32 years) with sickle cell disease but untreated were used to confirm the antisickiing properties of the present herbal formulation using the method described above. The results clearly confirmed the excellent efficacy of this purely herbal composition in preventing sickling of RBCS. The polyherbal formulation (T AYU H) exhibited 26.99+-1.94%,32.37+-1.13%,

37.56+-2.73% and 53.00+-2.95% antisickling activity at concentrations of l0ug/ml, 25ug/ml,50 ug/ml, and l00ug/ml respecrively.(TABLE2,3,4,graphl,&2)
Thirty patients suffering from sickle cell disease with symptoms were successfully treated with the herbal combination of the present invention. The usual dose was 300mg of oral preparation containing ingredients as per the concentrations mentioned earlier (tablel) preferably in the tablet form twice a day for adults. Children could be given 300mg. once a day (ie .half of normal the adult dose ).There was dramatic improvements in the patients conditions were observed with respect to reduction or freedom from symptoms. The minimum duration of therapy required in most of the cases was 3months while severe cases may require long term or even life long therapy with the combination.

CLAIMS:
I claim;
1 .A polyherbal composition for the treatment of sickle cell disease comprising of Aloe vera, Amlaki (Phyllanths emblica )Jaiphal (Myristica fragrans houtt), Sunthi(Zingiber Officinal Roscoe), Jivanti Ghana (Leptadenia reticulate), Haritaki Ghana (Terminalia Chebula), Guduchi Ghana (Tinospora cordifolia), Shatavari Ghana (Asparagus racemosus), Dadima (Punica granatum.Linn), Pippali
(Piper longum linn), Chitrak(Plumbago Zeylanica) 2. The polyherbal composition according to claim 1 wherein the prefered
concentration Aloe vera is 50mg., Amlaki (Phyllanths emblica )is 50mg., Jaiphal (Myristica fragran houtt) is 12.5mg., Sunthi(Zingiber Officinal Roscoe) is 25mg., Jivanti Ghana (Leptadenia reticulate) is 12.5mg., Haritaki Ghana (Terminalia Chebula) is 25mg., Guduchi Ghana (Tinospora cordifolia) is 12.5mg., Shatavari
Ghana (Asparagus racemosus) is 25mg., Dadima (Punica granatumXinn) is
12.5mg., Pippali (Piper longum linn) is 25mg., Chitrak(Plumbago zeylanica) is 12.5mg.
3 The polyherbal composition according to claim 1 or claim 2 for administration by the oral route.
4 The polyherbal composition according to claim3 in the form of liquid, powder, granules, ,tablets or capsules and preferably in the form of tablets.
with appropriate excipients.

5. The polyherbal composition according to claim 4 for administration to an adult
preferably twice a day.
6. The polyherbal composition according to claim 4 for administration to a child
preferably once a day.
7 A method of treating Sickle cell disease by orally administering to a human in need of treatment for sickle cell disease a herbal composition comprising of Aloe vera, Amlaki (Phyllanthsemblica )Jaiphal (Myristica fragrans houtt), Sunthi(Zingiber Officinal Roscoe), Jivanti Ghana (Leptadenia reticulate), Haritaki Ghana (Terminalia Chebula), Guduchi Ghana (Tinospora cordifolia), Shatavari Ghana (Asparagus racemosus), Dadima (Punica granatum.Linn), Pippali (Piper longum linn), Chitrak(Plumbago Zeylanica )
8...The method of treating sickle cell disease according to claim 7 where in preferred concentration Aloe vera is 50mg., Amlaki (Phyllanthsemblica )is 50mg., Jaiphal (Myristica fragran houtt) is 12.5mg., Sunthi(Zingiber Officinal Roscoe) is 25mg., Jivanti Ghana (Leptadenia reticulate) is 12.5mg., Haritaki Ghana (Terminalia Chebula) is 25mg., Guduchi Ghana (Tinospora cordifolia) is 12.5mg., Shatavari Ghana (Asparagus racemosus) is 25mg., Dadima (Punica granatum.Linn) is 12.5mg., Pippali (Piper longum linn) is 25mg., Chitrak(PIumbago zeylanica) is 12.5mg.
9. The method of treating sickle cell disease according to claim 8 where in
the composition is orally administered in the form of liquid, suspension, powder,

granules, ,tablets or capsules and preferably in the form of tablets. with appropriate excipients.
10. The method of treating sickle cell disease according to claim 9 where in the
composition is administered in one to three times per day for adults.
11. The method of treating sickle cell disease according to claim 10 where in the composition is administered two times a day .for adults.
12. The method of treatig sickle cell disease according to claim 9 where in the composition is administered preferably once a day to children.