FORM 2
THE PATENTS ACT, 1970 (39 OF 1970) PROVISIONAL/COMPLETE SPECIFICATION
[ See section 10]



1. Title of the invention.
2. Repeat the columns (a) to (c) if there are more than one applicant.
3. Insert the name in full.
The family or principal
name in the beginning if the
applicant is a natural person.

(a).3. (b).4. (c).5.

4.
Insert the complete address including postal index number / code, state and country.
5.
Insert the nationality.
6. Strike out in case of provisionsal specification.
7. Description of the invention.
8.1napplicable in case of provisional specification.


The following specification (particularly).6....
describes.6 the nature of the invention and
the manner in which it is to be perfbrmed.6...
3. .7.
3. I/We claim:-.8...
Dated this day of. 19/20.
Signature..9...

9. To be signed by the applicant or his authorised registered patent agent.
10. Name of the natural person who has signed.
11. (a) Not applicable in case of provisional specification, (b) Separate sheet to be used for this column

5...11.
Abstract of the invention,
To
The Controller of Patents
The Patent Office,
at

Note: Strike out whichever is inapplicable


INDUSTRIAL PROCESS FOR MANUFACTURING HYDROXYUREA
The various names of the product "hydroxyurea" for which novel process has been invented are:
1. Carbamoyl Hydroxylamine
2. Carbamohydroxamic Acid
3. N (Amino Carbonyl) hydroxylamine
4. N - Carbamoyl hydroxylamine
5. Hydroxycarbamide
Hydroxyurea has molecular weight 76.055 and molecular formula CH4N2O2. The chemical structure is as per below:

Prior Art:
Hydroxyurea is a white crystalline powder with melting point of 70 - 72°C. It can exist as dimarph, which melt at 141°C It is hygroscopic and gets decomposed very rapidly in aqueous acidic medium, whereas its metallic salts are stable. It is insoluble in Diethyl Ether and Benzene.
Hydroxyurea is normally administered in capsule form. Its indicated for melanoma, resistant chromic myelocytic leukemia, carcinoma at of ovary. It is regular dosage is 80 mg / kg as a single dose every third day. Alternatively, it is administered 20 to 30 mg / kg as a singe dose daily.
In organic synthesis, collective volume 5 at page 645, synthetic process of hydroxyurea is detailed as per follows:
'To a solution of Hydroxylamine Hydrochloride and Sodium Hydroxide in water urethane is added. The reaction is allowed to continue for 3 days after which the reaction mixture is neutralized and extracted with ether. The product is isolated from aqueous phase by vacuum distillation."
The alternative route of synthesis based on reaction of Sodium Cyanate with Hydroxylamine Hydrochloride has been described by various investigators such as W.F.C. Fresler etal. Ann. 150, 242 (1869), L. Francesconl etal, 4022. Chim. Ital. 31, 11, 334 (1901), H. Kofod, Acta Chem Scand 7,274,938(1953).

However the product obtained from the above methods lack purity and stability. The product develops pink to Yellow Spots on drying and Storage.
However, mere are no patents on the synthesis of Hydroxyurea. British patent 930844 dated 10/07/1963 describes the synthesis of various urea derivatives such as l-Hydroxy-3-ethylurea, 1,3-dimethyl-1 -methoxyurea, 1,1 -dibutyl-3-methyl-3 -methoxyurea, 1 -methyl-1 -methoxyurea. However, it does not describe synthesis of described compound Hydroxyurea.
Present Invention:
The objective of present invention was to improve the reported method based on reaction of Sodium Cyanate and hydroxylamine to provide a product which is in the form of white crystalline powder and which meets current B.P. (2002) and USP (2002) requirements and which is stable on storage. The other objective of present invention was to scale up the process of regular industrial production using simple set up consisting glass reactor, centrifuge and hot air dryer.
It has now surprisingly found that previous disadvantages such as colour development during synthesis, Noncompliance to phannacopeal standards, hazardous conditions during synthesis can be avoided.
Example:
Approximately 77 kgs of commercial grade of Sodium Cyanate was mixed with 20 kg of hydroxylamine salt in a suitable liquid medium. The reaction mixture was stirred at temperature not exceeding 45°C. After the reaction was complete, the reaction medium was distilled out under vacuum. The residue was purified using Ethanol to get the final product complying to pharmacopeal norms. The identity and purity of the material was confirmed as per B.P. 2002. The minimum yield based on the main raw materials was 30%.

Claims:
1. Manufacturing process for hydroxyurea based on reaction of Sodium cyanate and Hydroxylamine Salts..
2. The product complies with BP 2002 and USP 2002 norms in all respects.
3. Process as claimed in Claim 1 can be carried out at industrial scale using simple set up such as glass reactor, centrifuge hot air dryer.

4. Process as claimed in claim 1 provide the product, which is in the form of white crystalline powder, which does not change colour on storage for a long time. The product is devoid of pink-yellow spots.
5. Process for preparing Hydroxyurea for pharmaceutical use as herein described.