FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rule l3)
1. TITLE OF THE INVENTION:
"LIQUID PHARMACEUTICAL COMPOSITION OF CHOLINE
ALFOSCERATE"
2. APPLICANT
(a) NAME: Lyka Labs Limited.
(b) NATIONALITY: Indian Company incorporated under the
Indian Companies ACT, 1956
(c) ADDRESS: 101, Shivshakti Industrial Estate, Andheri-Kurla Road,
Andheri (East), Mumbai - 400059, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION
The following specification describes the invention:

Technical field of invention:
The present invention relates to an Oral Liquid Pharmaceutical Composition in two forms, sugar free syrup and sugar syrup containing Choline Alfoscerate which acts as psycostimulant, a stimulator of Central Nervous System in elder patient.
Background of the invention:
Choline Alfoscerate also known as Alpha GPC (L-.alpha.-glycerophosphorylcholine) is a phospholipids metabolite found concentrated in neuronal membranes made from lecithin, Alpha GPC is extremely well absorbed and crosses the blood brain barrier.
GPC is produced on a commercial scale by biochemical processes, generally starting from lecithin and especially from soybean lecithin, and is absolutely biocompatible and non-toxic. GPC is highly soluble in water, has a sweet and agreeable taste, and is commercially available in the anhydrous form as a highly hygroscopic powder, although it is preferably marketed in the monohydrate form as a stable syrupy liquid.
Alpha GPC supports brain function and learning processes by directly increasing the synthesis and secretion of acetylcholine. Alpha GPC protects neurons and improves signal transmission by serving as a precursor to membrane phospholipids.
US Patent No. 6194401, discloses a pharmaceutical composition containing a cyclosporine as active ingredient, characterized in that it comprises a cyclosporine and as a carrier at least an ester of .alpha.-glycerophosphoric acid selected from the group consisting of .alpha.-glycerophorylcholine (choline alfoscerate), .alpha.-glycerophorylethanolamine, .alpha.-glycerophorylserine, .alpha.-glycerophorylinositol, salts and pharmaceutically acceptable complexes thereof. The said composition is suitable for oral administration in the form of packets, hard or soft capsules, tablets, or pills.


US Patent No. 5,516,798 discloses a method of treating diarrhea in a warm-blooded vertebrate animal comprising administering to said animal an effective amount of a methylamine selected from the group consisting of betaine, creatine, creatine phosphate, choline, phosphorylcholine, glycerophosphorylcholine (choline alfoscerate), and combinations thereof. The said formulation is in a fluid form, tablet form, powder form, and combinations thereof. Fluid form comprises a methylamine admixed in a liquid suitable therefor selected from the group consisting of water, a rehydration solution, nutritional fluid, and combinations thereof.
Object of the invention:
The main object of the invention is to provide an oral liquid pharmaceutical composition comprising Choline Alfoscerate along with the pharmaceutically acceptable excipients.
Another object of the present invention is to provide an oral liquid pharmaceutical composition in a form of sugar free syrup or sugar syrup containing Choline Alfoscerate, which acts as a psycostimulant, a stimulator of Central Nervous System in elder patient and process for preparation thereof.
Summary:
The present invention provides a Liquid Pharmaceutical Composition comprising of Choline Alfoscerate along with the pharmaceutically acceptable excipients selected from sugar alcohol, sweetener, flavours, colours, preservatives in a form of oral liquid dosage form, preferably in a form of syrup. The composition of the present invention is suitably formulated using pharmaceutical exicipients
In one embodiment, the present invention provides, a liquid pharmaceutical composition comprising Choline Alfoscerate in sugar free syrup.
In second embodiment, the invention provides a liquid pharmaceutical composition comprising Choline Alfoscerate in sugar syrup


In another embodiment, the present invention provides a process for the manufacture of Choline Alfoscerate composition which comprises of following steps:
i) Dissolving Choline Alfoscerate in purified water.
ii) Mixing Glycerine, sorbitol solution, Propylene Glycol and Butylated Hydroxy
Anisole in a container,
iii) Dissolving Methyl paraben, Propyl Paraben, Disodium EDTA and Saccarine
Sodium in purified water,
iv) Mixing the solution of Step 3 to Step 2.
v) Adding the drug solution of STEP 1 to STEP 4.
vi) Dissolving Quinoline yellow in Purified Water and adding to solution of
Step 5.
vi) Adding pineapple sweet flavour to solution of Step 6.
vii) Filter the solution of STEP 7 to make up the volume,
ix) Checking the pH and adjusting in the range if required.
Detailed description of the invention:
The present invention describes liquid pharmaceutical composition comprising of Choline Alfoscerate in the form of sugar free syrup or sugar syrup which is useful as a psycostimulant, stimulator of Central Nervous System in elder patient.
In accordance to the above objectives a pharmaceutical composition comprises
therapeutically effective amount of Choline Alfoscerate along with pharmaceutical^
accepted excipients selected from sugar alcohol, sweetener, flavours, colours,
preservatives in the form of Liquid form such as syrup and the process of preparation
thereof.
Choline Alfoscerate used in the pharmaceutical composition is in the range of l00mg to
500mg /5ml.
Sugar alcohol is selected from Glycerine, Proppylene Glycol and Sorbitol alone or in combination thereof in the range of 10-90%.


Suitable Sweetener such as Sodium saccharine, Sorbitol in the range of 0.1- 70 %. Suitable colours may be chosen such as Quinoline Yellow Supra, Ponceau 4R supra, in the range of 0.005-0.2%.
Suitable flavours may be used such as pineapple sweet flavour, in the range of 0.5-1.0%.
Suitable preservatives may be used such as sodium benzoate, methyl paraben and propyl paraben. Methyl paraben may be used in the range of 0.0-0.1%. Propyl paraben may be used in the range of 0.0-0.01%.
Disodium EDTA may be used in the range of 0.05%).
Antioxidant such as Butylated Hydroxy Anisole in the range of 0.0-0.1%.
The invention can be illustrated by the following non-limiting examples:
Examples:
Example 1: Composition (For Sugar free syrup):
Choline Alfoscerate: 400 mg / 5 ml Flavoured Base ... q.s.
The typical ingredients for Batch of 1 liter are

Sr.No. Ingredients Range/amount In% Amount for 1 liter Batch
1. Choline Alfoscerate 400mg/5ml 95 gm

2. Glycerine 15%w/v 150 gm

3. Propylene Glycol 1.5%w/v 15 gm

4. Sorbitol 70% solution 67.5%w/v 675 gm

5. Disodium EDTA 0.05%w/v 0.5 gm

6. Sodium saccharine 0.3%w/v 3.0 gm



7. Pineapple sweet flavour 0.75%v/v 7.5 ml

8. Methyl paraben 0.072%w/v 0.72 gm

9. Propyl paraben 0.0072%w/v 0.072 gm

10. Butylated hydroxy Anisole 0.01%w/v 0.1 gm

11. Colour: Quinoline Yellow 0.006%w/v 0.06gm

12. Purified water q.s q.s. to 1 It

The process for manufacturing of Choline Alfoscerate sugar free syrup is as follows.
STEP 1:
Weighing Choline Alfoscerate and dissolving the same in 100ml of Purified Water.
STEP 2:
Weighing Glycerine in a container and adding Sorbitol solution and Propylene Glycol and Butylated Hydroxy Anisole under stirring.
STEP 3:
Dissolving Methyl paraben, Propyl Paraben, Disodium EDTA and Saccarine Sodium in 40ml Purified Water by heating
STEP 4:
Adding solution of STEP 3 to STEP 2
STEP 5:
Adding the drug solution of STEP 1 to bulk solution of STEP 4 under stirring
STEP 6:


Dissolving Quinoline yellow in minimum amount of Purified Water and adding the same to bulk solution of STEP 5 under stirring
STEP 7:
Adding pineapple sweet flavour to the bulk of STEP 6 under stirring
STEP 8:
Filtering the solution of STEP 7 and make up the volume with purified water.
STEP 9:
Checking the pH and adjusting in the range if required.
Example 2: Composition (with sugar):
Choline Alfoscerate: 400 mg / 5 ml Flavour Syrupy Base: q.s. The typical ingredients for Batch of 1 litre are

Sr.No. Ingredients Range/amount Amount for 1 liter Batch
1. Choline Alfoscerate 400mg/5ml 95 gm

2. Sugar Pharma grade 50% w/v 500 gm

3. Propylene Glycol 5% w/v 50 gm

4. Methyl paraben 0.072%w/v 0.72 gm

5. Propyl paraben 0.0072%w/v 0.072 gm

6. Disodium EDTA 0.05%w/v 0.5 gm

7. Colour : Sunset Yellow 0.01%w/v 100 mg

8. Flavour: Juicy Mango 0.75%v/v 7.5 ml

9. Purified water q.s q.s. to 1 It



The process for manufacturing of Choline Alfoscerate with sugar syrup is as follows: STEP 1:
Taking 250 ml of Purified Water and heat it to boil. Adding and dissolving Disodium EDTA and sugar.
STEP 2:
Weighing Choline Alfoscerate and dissolving the same in 100ml of Purified Water and add it to (Step 1)
STEP 3:
Dissolving Methyl Paraben and Propyl Paraben into Propylene Glycol and adding the same to STEP 2.
STEP 4:
Dissolving colour Sunset Yellow in minimum amount of Purified Water and adding the same to bulk of STEP 3 under stirring.
STEP 5:
Adding Juicy Mango flavour to the bulk of STEP 4 under stirring.
STEP 6:
Filtering the solution of STEP 6 and make up the volume with purified water.
STEP 7:
Check the pH and adjust within the range if required