Indian Patents. 182481:A PROCESS FOR PREPARING A SYNERGISTIC PHARMACEUTICAL COMPOSITION FOR DELAYING CATARACTOGENESIS

Title of Invention	A PROCESS FOR PREPARING A SYNERGISTIC PHARMACEUTICAL COMPOSITION FOR DELAYING CATARACTOGENESIS
Abstract	* Abstract This Invention relates to a process for preparing a synergestic pharmaceutlcal composition for delaying cataractogenesls by blending amino acids, vitamins, antioxidants an d micro-sutrients like sodium selinlte in a given range.

Full Text	This invention relates to a process for preparing a synergestic pharmaceutical composition for delaying cataractogenesis. Opacity of the lens of the eye as a result of degenerative changes in it causes cataract. Due to various factors the normally transparent crystalline lens of the eye becomes opaque which in turn impedes the light rays from entering the eye, result ing in gradual loss of vision or blindness. It has now been established that cataract formation which is largely due to ageing, can be delayed considerably by the intake of certain micro-nutrients, vitamins and minerals. Researchers have found that micro-nutrients like Riboflavin, Zinc, Selenium Iron and Copper are useful in delaying cataractogenesis. Recent studies have shown increased oxidative stress or activity in human metabolic system during the onset of browning of the lens during brunescent cataract. Introduction of antioxidant micro-nutrients as dietary supplement, delays the onset of oxidative degeneration of the lens. Intracellular and extracellular antioxidant propeties of vitamins like ascorbic acid, alphatocopherol and betacarotene have already been established by research studies. Deficiency of amino acids like phenylalanine, histidine, leucine, isoleucine, valine, threonine, lysine and methionine may also lead to lens degeneration, vascularization of cornea and resultant lens damage. Glycine and Lysine are also found to be important in delaying cataract onset in both normal and diabetic patients. The mechanism by which Lysine and Glycine work is by scavenging glucose resulting in the decrease of gtycat ion of lens proteins. Lysine, glycine, glutamic acid and inositol exhibit antioxidant and antigIycating proper t i es, while alanine, ascorbic acid and pyridoxin show on 1y antigiycating properties. Tocopherol and carotenoids exhibit strong antioxidant properties. Deficiency of any of these nutrients hastens cat arac t'ogenesis in the elderly and the object of this invention is in providing a stable, synergestic and mutually compIimentary dietary supplement for delaying the onset of cataract. Adminstratjon of any of the above referred micro-nutrJents individually does not always produce the desired result of delaying cataractogenesis. We have found that a compos i t ion of micro-nutrients in a given range exhibits properties fundament ally different from the compound ing ingredients and shows synergistic and reinforced properties as these component s compliment each other in metabolic activity, glucose scavenging, and antioxidation. This composition is found effect!ve in delaying cataractogenesis in both normal and diabetic patients and is a dietary suppliment augmenting immunity and, promoting genera I heaIth. This invention relates to a process for preparing a synergistic pharmaceutical compos ition for del aying cataractogenesis which comprises blending compounds listed hereinunder in the ranges specified thereagainst with known adjuvants and/or excipients. L - Tryptophan 1.7 to 3.5 mg L - Valine 2.3 to 4.4 mg I. - Lysine 35 to 65 mg L - Phenylalanine 1.7 to 3.3 mg L - Histidine , 1.4 to 3.3 mg L - Alanine 35 to 65 mg L-AsparticAcid 5.25to9.8mg Glycine 3.5to6.5 mg L - Giutatnic Acid 35 to 65 mg 1, - Cysteine 5.25 to 12 mg Tocopherol Acetate 3.5 to 6.5 mg AscorbicAcid I7to35 mg [nos i to I 35 to 65 mg Pyridoxin HcJ 1 to 2 mg Riboflavin 1 to 2 mg Copper Sulphate 0.3 to 0.6 mg Zinc Sulphate 5 to 10 mg Sodium Ketinite 17 to 33 meg Conventional additives, colorants and excipients are added depending upon the nature of the compos ition. If a liquid composition is preferred, adjuvants like distilled water and pharmaceutically acceptable solvents are used and the active ingredients specified above are either emuEsified or dissolved therein. Tablets or capsules are prepared by suitable substitution of so 1 id adjuvants. The compound ing ingredients may be thoroughly mixed and tabletted in the conventional manner. Capsules may also be formed wherien the active ingredients are spheronised and encapsulated in a shell made of pharmaceutically acceptable bio¬degradable material. Commonly used excipients or adjuvants and colorants are given be low; Col. Tartrazine Col. Indigo Carmine Col. Erythrosine Col. Sunset Ye I low Titanium Dioxide, Lactose, Potato Starch, Microcrystal1ine Cellulose, Calcium Carboxymethy1 Cellulose, Methyl Cellulose, Hydroxypropy1 Cellulose, Polyethylene Glycol 6000, Synthetic Aluminium Silicate, Stearic acid. Industrial Methylated Spirit, Polyvinyl Pyrrolidone, Iso Propyl Alcohol and Distilled water, Maize Starch, Purified water. In a preferred embodiment, compat ib1e components of the composition are grouped together, spheronised, dried and encapsulated. For example, a capsule may contain a plurality of granules, the total composition of which falls within the range specifiecJ herein above, but each group of granules may contain a group of compatible components different from the other group. For instance, a capsule may contain whi te, yellow, red, chocolate blue, rose, green and orange granules of the composition specified herein below. Ye I 1ow Granules: - VaIine 3.35 mg , - Lysine He 1 62.5 mg . - Phenylalanine 2.5 mg . - Histidine Hcl 3.24 mg . - Alan ine 50.0 mg Glycine 5.00 mg Microcrystalline Cellulose 15.21 mg Potato Starch 15.0 mg Methyl Cellulose 4.75 mg Hydroxy Propyl Cellulose 1.0 mg Coi. Tartrazine 0.45 mg Water DistiHed O.OJml The above components are mixed in a planetary mixer for one hour and water is added slowly to obtain a soft mass. This is passed through an extruder and then spheronlsed, using murmeriser. The spheronised granules are dried at 45° for about an hour till moisture content is reduced to less than 1%. H. White Granules: Copper sulphate 0.42 mg Zinc su1phate 7.8 mg Rodium Selenite 25 meg Maize Starch 2R mg Micro Crystalline Cellulose 10 mg Methyl Cellulose .1.8 mg Lactose 10 mg Water Purified O.Ol ml The above ingredients are mixed and granulated as stated in connection with the preparation of Yellow Granules (No.I) 11T. Blue Granules: Ascorbic Acid ' 35 mg Stear i c Acid 1.05 mg Industrial Methylated Spirit 0.005 ml Potato Starch 3.65 mg Micro Crystalline Cellulose 1.75 mg Polyethylene Glycol 6000 1.2 mg Calcium Carboxy Methyl Cellulose 1.7 mg Methyl Cellulose 0.6 mg Co lour Ind i go Carmine 0.05 mg Water Purified 0.01 ml The above ingredients are blended and spheronised as stated under Yellow Granules (No.1) IV. Rose Granules: Tocopherol Acetate 5.5 mg I. - Tryptophan ' 3-5 mg !, - Cystein 12.0 mg Synthetic Aluminium Silicate 4.0 mg Microcrystal1ine Cellulose 2.5 mg Polyethylene Glycol 6000 0.14 mg Hydroxy Propyl Cellulose 2.5 mg Calcium Carboxy Methyl Cellulose 2.7 mg Lactose 16.5 mg Colour Erythrosine 0.15 mg Colour Tartrazine 0.01 mg Water Purified O.OI ml The above ingredients are mixed and; spheronised as stated herein above. V. Orange Granules: Inositol 60 iDg Pyridoxine Hcl 1.876 ng Riboflavin 1.876 mg Potato Starch 8.748 mg Microcrystal1ine Cellulose 10.0 mg Polyethylene Glycol 6000 0.5 mg Caiciun Carboxy Methyl Cellulose 6.0 mg Hydroxy Propyl Cellulose 1.0 mg Water Purified 0.01 ml The above ingredients are blended and spheronised in a manner as stated herein above. Quantities of Vitamin mentioned in the process are inclusive of required averages. VI, Green Granules: L - Aspartic Acid 7.5 mg L - Glutamic Acid SO mg Microcrystalline Cellulose 8.2 mg Potato Starch 8.02 mg Methyl Cellulose 4.0 mg Hydroxy Propyl Cellulose 0.5 mg Colour Tartrazine 0.2S mg Colour Indigo Carmine 0.03 mg Water Purified 0.01 ml Spheronised granules are made from the above ingredients as stated hereinabove. VII. White Dummy Granules: Lactose 47.52 mg Mai/e Starch 6.08 mg Microcrystal1ine Cellulose 12.88 mg Methyl Cellulose 1.22 mg Water Purified 0.05 ml Dummy Granu)es are spheronised using the above quantities of ingredients. Capsules are prepared by mixing the desired quantities of granules under items 1 to 7 in the conventional manner. Obvious variations and equivalents are well witfiin the scope of this invention. I w We Claim: 1- A process for preparing a synergistic pharmaceutica1 composition for delaying cataractogenesis compr ising blending compounds listed hereinunder in the ranges specified thereagainst with known adjuvants and/or excipients. L - Tryptophan 1.7 to 3.5 mg L - Valine 2.3 to 4.4 mg L - Lysine 35 to 65 mg L - Phenylalanine 1.7 to 3.3 mg L-Histidine 1.4to3.3mg L - Alanine 35 to 65 mg 1, - Aspartic Acid 5.25 to 9.8 mg Glycine 3.5to6.5mg L-GlutamicAcid 35to65 mg L - Cysteine 5.25 to 12 mg Tocopherol Acetate 3.5 to 6.5 mg Ascorbic Acid 17 to 35 mg Inositol 35 to 65 mg Pyridoxin Hcl 1 to 2 mg Riboflavin 1 to 2 mg Copper Sulphate 0.3 to 0.6 mg Zinc Sulphate 5 to 10 mg Sodium Selinide 17 to 33 meg 2. The process as claimed in claim 1, wherein the said compounds are blended to form an emulsion or suspension in known pharmaceutically acceptable adjuvants. 3. The process as claimed in claim 1 where in the compounds are tabletted after blending. 4. The process as claimed in claim I wherein the compounds are granulated and then encapsulated in a pharmaceutica1ly acceptable biodegradable casing. 5. The process as claimed in claims 1 to 4 wherein compatible compounds are blended together, spheronised to form granules, and then further blended before encapsulation. 6. The process as claimed in claims 1 & 5 wherein pharmaceutically acceptable colorants are added. 7. The process as claimed in claims 5 & 6 wherein different colorants are added to each group of spheronised granules. 8. The process as claimed in claims 5 to 7 wherein the granules are dried at 45 C to a moisture con tent of less than 1%. 9. A process for preparing a synergistic pharmaceutical composition for delaying cateractogenesis substantially as herein descr i bed.

Full Text

This invention relates to a process for preparing a synergestic pharmaceutical composition for delaying cataractogenesis.
Opacity of the lens of the eye as a result of degenerative changes in it causes cataract. Due to various factors the normally transparent crystalline lens of the eye becomes opaque which in turn impedes the light rays from entering the eye, result ing in gradual loss of vision or blindness. It has now been established that cataract formation which is largely due to ageing, can be delayed considerably by the intake of certain micro-nutrients, vitamins and minerals.
Researchers have found that micro-nutrients like Riboflavin, Zinc, Selenium Iron and Copper are useful in delaying cataractogenesis. Recent studies have shown increased oxidative stress or activity in human metabolic system during the onset of browning of the lens during brunescent cataract. Introduction of antioxidant micro-nutrients as dietary supplement, delays the onset of oxidative degeneration of the lens. Intracellular and extracellular antioxidant propeties of vitamins like ascorbic acid, alphatocopherol and betacarotene have already been established by research studies. Deficiency of amino acids like phenylalanine, histidine, leucine, isoleucine, valine, threonine, lysine and methionine may also lead to lens degeneration, vascularization of cornea and resultant lens damage. Glycine and Lysine are also found to be important in delaying cataract onset in both normal and diabetic patients. The mechanism by which Lysine and Glycine work is by scavenging glucose resulting in the decrease of gtycat ion of lens proteins. Lysine, glycine,

glutamic acid and inositol exhibit antioxidant and antigIycating proper t i es, while alanine, ascorbic acid and pyridoxin show on 1y antigiycating properties. Tocopherol and carotenoids exhibit strong antioxidant properties.
Deficiency of any of these nutrients hastens cat arac t'ogenesis in the elderly and the object of this invention is in providing a stable, synergestic and mutually compIimentary dietary supplement for delaying the onset of cataract. Adminstratjon of any of the above referred micro-nutrJents individually does not always produce the desired result of delaying cataractogenesis. We have found that a compos i t ion of micro-nutrients in a given range exhibits properties fundament ally different from the compound ing ingredients and shows synergistic and reinforced properties as these component s compliment each other in metabolic activity, glucose scavenging, and antioxidation. This composition is found effect!ve in delaying cataractogenesis in both normal and diabetic patients and is a dietary suppliment augmenting immunity and, promoting genera I heaIth.
This invention relates to a process for preparing a synergistic pharmaceutical compos ition for del aying cataractogenesis which comprises blending compounds listed hereinunder in the ranges specified thereagainst with known adjuvants and/or excipients.
L - Tryptophan 1.7 to 3.5 mg
L - Valine 2.3 to 4.4 mg
I. - Lysine 35 to 65 mg

L - Phenylalanine 1.7 to 3.3 mg
L - Histidine , 1.4 to 3.3 mg
L - Alanine 35 to 65 mg
L-AsparticAcid 5.25to9.8mg
Glycine 3.5to6.5 mg
L - Giutatnic Acid 35 to 65 mg
1, - Cysteine 5.25 to 12 mg
Tocopherol Acetate 3.5 to 6.5 mg
AscorbicAcid I7to35 mg
[nos i to I 35 to 65 mg
Pyridoxin HcJ 1 to 2 mg
Riboflavin 1 to 2 mg
Copper Sulphate 0.3 to 0.6 mg
Zinc Sulphate 5 to 10 mg
Sodium Ketinite 17 to 33 meg
Conventional additives, colorants and excipients are added depending upon the nature of the compos ition. If a liquid composition is preferred, adjuvants like distilled water and pharmaceutically acceptable solvents are used and the active ingredients specified above are either emuEsified or dissolved therein.
Tablets or capsules are prepared by suitable substitution of so 1 id adjuvants. The compound ing ingredients may be thoroughly mixed and tabletted in the conventional manner. Capsules may also be formed wherien the active ingredients are spheronised and encapsulated in a shell made of pharmaceutically acceptable bio¬degradable material.

Commonly used excipients or adjuvants and colorants are given be low;
Col. Tartrazine
Col. Indigo Carmine
Col. Erythrosine
Col. Sunset Ye I low
Titanium Dioxide, Lactose, Potato Starch, Microcrystal1ine
Cellulose, Calcium Carboxymethy1 Cellulose, Methyl Cellulose,
Hydroxypropy1 Cellulose, Polyethylene Glycol 6000, Synthetic
Aluminium Silicate, Stearic acid. Industrial Methylated Spirit,
Polyvinyl Pyrrolidone, Iso Propyl Alcohol and Distilled water,
Maize Starch, Purified water.
In a preferred embodiment, compat ib1e components of the composition are grouped together, spheronised, dried and encapsulated. For example, a capsule may contain a plurality of granules, the total composition of which falls within the range specifiecJ herein above, but each group of granules may contain a group of compatible components different from the other group. For instance, a capsule may contain whi te, yellow, red, chocolate blue, rose, green and orange granules of the composition specified herein below.
Ye I 1ow Granules:
- VaIine 3.35 mg
, - Lysine He 1 62.5 mg
. - Phenylalanine 2.5 mg
. - Histidine Hcl 3.24 mg
. - Alan ine 50.0 mg
Glycine 5.00 mg

Microcrystalline Cellulose 15.21 mg
Potato Starch 15.0 mg
Methyl Cellulose 4.75 mg
Hydroxy Propyl Cellulose 1.0 mg
Coi. Tartrazine 0.45 mg
Water DistiHed O.OJml
The above components are mixed in a planetary mixer for one hour and water is added slowly to obtain a soft mass. This is passed through an extruder and then spheronlsed, using murmeriser. The spheronised granules are dried at 45° for about an hour till moisture content is reduced to less than 1%.
H. White Granules:
Copper sulphate 0.42 mg
Zinc su1phate 7.8 mg
Rodium Selenite 25 meg
Maize Starch 2R mg
Micro Crystalline Cellulose 10 mg
Methyl Cellulose .1.8 mg
Lactose 10 mg
Water Purified O.Ol ml
The above ingredients are mixed and granulated as stated in connection with the preparation of Yellow Granules (No.I)
11T. Blue Granules:
Ascorbic Acid ' 35 mg
Stear i c Acid 1.05 mg
Industrial Methylated Spirit 0.005 ml

Potato Starch 3.65 mg
Micro Crystalline Cellulose 1.75 mg
Polyethylene Glycol 6000 1.2 mg
Calcium Carboxy Methyl Cellulose 1.7 mg
Methyl Cellulose 0.6 mg
Co lour Ind i go Carmine 0.05 mg
Water Purified 0.01 ml
The above ingredients are blended and spheronised as stated under Yellow Granules (No.1)
IV. Rose Granules:
Tocopherol Acetate 5.5 mg
I. - Tryptophan ' 3-5 mg
!, - Cystein 12.0 mg
Synthetic Aluminium Silicate 4.0 mg
Microcrystal1ine Cellulose 2.5 mg
Polyethylene Glycol 6000 0.14 mg
Hydroxy Propyl Cellulose 2.5 mg
Calcium Carboxy Methyl Cellulose 2.7 mg
Lactose 16.5 mg
Colour Erythrosine 0.15 mg
Colour Tartrazine 0.01 mg
Water Purified O.OI ml
The above ingredients are mixed and; spheronised as stated herein above.

V. Orange Granules:
Inositol 60 iDg
Pyridoxine Hcl 1.876 ng
Riboflavin 1.876 mg
Potato Starch 8.748 mg
Microcrystal1ine Cellulose 10.0 mg
Polyethylene Glycol 6000 0.5 mg
Caiciun Carboxy Methyl Cellulose 6.0 mg
Hydroxy Propyl Cellulose 1.0 mg
Water Purified 0.01 ml
The above ingredients are blended and spheronised in a manner as
stated herein above. Quantities of Vitamin mentioned in the
process are inclusive of required averages.
VI, Green Granules:
L - Aspartic Acid 7.5 mg
L - Glutamic Acid SO mg
Microcrystalline Cellulose 8.2 mg
Potato Starch 8.02 mg
Methyl Cellulose 4.0 mg
Hydroxy Propyl Cellulose 0.5 mg
Colour Tartrazine 0.2S mg
Colour Indigo Carmine 0.03 mg
Water Purified 0.01 ml
Spheronised granules are made from the above ingredients as stated hereinabove.

VII. White Dummy Granules:
Lactose 47.52 mg
Mai/e Starch 6.08 mg
Microcrystal1ine Cellulose 12.88 mg
Methyl Cellulose 1.22 mg
Water Purified 0.05 ml
Dummy Granu)es are spheronised using the above quantities of ingredients.
Capsules are prepared by mixing the desired quantities of granules under items 1 to 7 in the conventional manner.
Obvious variations and equivalents are well witfiin the scope of this invention.
I
w

We Claim:
1- A process for preparing a synergistic pharmaceutica1 composition for delaying cataractogenesis compr ising blending compounds listed hereinunder in the ranges specified thereagainst with known adjuvants and/or excipients.
L - Tryptophan 1.7 to 3.5 mg
L - Valine 2.3 to 4.4 mg
L - Lysine 35 to 65 mg
L - Phenylalanine 1.7 to 3.3 mg
L-Histidine 1.4to3.3mg
L - Alanine 35 to 65 mg
1, - Aspartic Acid 5.25 to 9.8 mg
Glycine 3.5to6.5mg
L-GlutamicAcid 35to65 mg
L - Cysteine 5.25 to 12 mg
Tocopherol Acetate 3.5 to 6.5 mg
Ascorbic Acid 17 to 35 mg
Inositol 35 to 65 mg
Pyridoxin Hcl 1 to 2 mg
Riboflavin 1 to 2 mg
Copper Sulphate 0.3 to 0.6 mg
Zinc Sulphate 5 to 10 mg
Sodium Selinide 17 to 33 meg
2. The process as claimed in claim 1, wherein the said
compounds are blended to form an emulsion or suspension in known
pharmaceutically acceptable adjuvants.

3. The process as claimed in claim 1 where in the compounds are tabletted after blending.
4. The process as claimed in claim I wherein the compounds are granulated and then encapsulated in a pharmaceutica1ly acceptable biodegradable casing.
5. The process as claimed in claims 1 to 4 wherein compatible compounds are blended together, spheronised to form granules, and then further blended before encapsulation.

6. The process as claimed in claims 1 & 5 wherein pharmaceutically acceptable colorants are added.
7. The process as claimed in claims 5 & 6 wherein different colorants are added to each group of spheronised granules.
8. The process as claimed in claims 5 to 7 wherein the granules
are dried at 45 C to a moisture con tent of less than 1%.
9. A process for preparing a synergistic pharmaceutical
composition for delaying cateractogenesis substantially as herein
descr i bed.

Documents:

2234-mas-1997 abstract.pdf

2234-mas-1997 claims.pdf

2234-mas-1997 correspondnece-others.pdf

2234-mas-1997 correspondnece-po.pdf

2234-mas-1997 description(complete).pdf

2234-mas-1997 form-1.pdf

2234-mas-1997 form-26.pdf

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Patent Number

182481

Indian Patent Application Number

2234/MAS/1997

PG Journal Number

30/2009

Publication Date

24-Jul-2009

Grant Date

05-Nov-1999

Date of Filing

08-Oct-1997

Name of Patentee

M/S. TABLETS (INDIA) LIMITED

Applicant Address

179 TH ROAD, CHENNAI 600 081

Inventors:

#	Inventor's Name	Inventor's Address
1	RAJAGOPAL THIRUVENGADAM	E-9, G.L.APT. 640TH ROAD, TONDIARPET, CHENNAI 600081
2	SHAIK MADHU SUHAN,	E-9, G.L.APT. 640TH ROAD, TONDIARPET, CHENNAI 600081

PCT International Classification Number

A61K31/195

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA