Title of Invention

"A HERBAL OPHTHALMIC FORMULATION OF CURCUMA LONGA FOR DELAYING THE ONSET AND PROGRESSION OF CATARACT"

Abstract A herbal ophthalmic formulation of Curcuma longa for delaying the onset and progression of cataract comprising: 0.01% to 5 % w/v of extract of rhizome of Curcuma longa and 0.1 %- 5 % w/v visco elastic substance and q.s distilled water
Full Text The present invention relates to a herbal ophthalmic formulation of Curcuma longa for delaying the onset and progression of cataract.
Background of the invention
Cataract is the leading cause of blindness in the world. In India alone the annual incidence of cataract blindness is about 3.8 million. The present level of surgical performance is in the order of about 1.6-1.9 million cataract operations as against 5-6 million required to clear the backlog. Although, cataract surgery is the most commonly performed procedure and is generally recognized as being one of the safest operations, there is a significant complication rate. For this reason, if an intervention is able to delay the onset of cataract by 10 years or so, the number of cataract operations can be reduced to nearly half.
Visual impairment in cataract results from opacity or light scattering produced most often by the formation of large protein aggregates in the lens. The process of aggregation involves variety of complex metabolic and physiological mechanisms, which act in combination to change the refractive index. Studies on lens proteins indicate that post translational modifications such as oxidation, glycation, Schiffs base formation, carbamylation, transamidation, phosphorylation, elevated calcium levels and proteolysis lead to lens opacification. These chemical changes can be regulated to maintain lens homeostasis and transparency. Thus, cataract is believed to be a disease that probably requires a chemical solution for its delay.
In vitro and in vivo studies with experimental animal models as well as the epidemiological studies conducted with selected human populations demonstrated a lower incidence of cataract in the groups consuming higher amount of ascorbate and other antioxidants. Reactive oxygen species (ROS) such as hydrogen peroxide, superoxide radical, singlet oxygen and hydroxy! radical are postulated to contribute to this process. ROS generate in the eye both enzymatically and photochemically. Endogenous defense mechanisms through scavenging of ROS by antioxidant enzymes like superoxide dismutase. glutathione peroxidase, catalase and glutathione-S-transferase, simultaneously protect the lens from oxidative damage. Besides, physiological antioxidants such as Vitamin C, Vitamin E and pyruvate also play an important role in protection of lens from oxidative damage.
Various substances with diverse chemical structures and properties have been reported to offer protection against cataract in different experimental models. However, the need of the long term treatment with such agents pose a serious impairment for successful accomplishment of clinical trials.
Medicinal plant based formulations are being used since long for a variety of diseases. Because of sufficient evidence that oxidative stfess plays a role in mechanism of cataractogenesis, there has been an increasing interest in the development of suitable antioxidant products of plant origin, that could be effective in delaying or preventing the formation of cataract. Flavonoids and related poly-phenols are antioxidants and also potent inhibitors of aldose reductase. Effect of methanolic extract and the alkaloidal components from several plants have been studied on lens aldose reductase activitiy, the key enzyme in diabetic cataract. Further, a decreased risk of cataract has been associated with consumption of tea, a major source of flavonoid quercetin. Quercetin has been shown to inhibit hydrogen peroxide-induced oxidation of
related poly-phenols are antioxidants and also potent inhibitors of aldose reductase. Effect of methanolic extract and the alkaloidal components from several plants have been studied on lens aldose reductase activitiy, the key enzyme in diabetic cataract. Further, a decreased risk of cataract has been associated with consumption of tea, a major source of flavonoid quercetin. Quercetin has been shown to inhibit hydrogen peroxide-induced oxidation of the lens proteins. Optimization of dietary intake of protective nutrients has been an effective approach towards reducing the incidence of cataract. A polyherbal preparation, Chyavanprash protects against steroid induced opacities in lens of chick embryo. Recently, possibilities of plant extracts inhibiting xanthine oxidase, the enzyme responsible for superoxide radical production, are under investigation for cataract. It is suggested that utilization of natural products may lead to better results with minimum side effects.
It is the object of the present invention to overcome the afore-mentioned disadvantages.
Further object of the present invention is to study antioxidant and anti cataract potential of herbal extracts and to evaluate anti cataract potential of herbal extracts in experimental models of cataract.
To achieve the aforesaid objectives the present invention provides a herbal ophthalmic formulation of Curcuma longa for delaying the onset and progression of cataract comprising:
0.01 % to 5 % w/v of extract of rhizome of Curcuma longa and 0.1%- 5 % w/v visco elastic substance and q.s distilled water
Said visco elastic substance is Hydroxy propyl methyl cellulose
The said ingredients are in the following proportions:
Curcuma longa - 0.02 % w/v and
visco elastic substance - 0.25 % w/v
The ingredients are in the following proportions:
Curcuma longa - 0.01% w/v and
visco elastic substance - 0.25 % w/v
DETAILED DESCRIPTION OF THE INVENTION:
The following methodology was followed for the preparation of eye drops:
Step 1: Washing of the eye drop containers (glass vials)
The glass vials were first washed with teepol solution rinsed with tap water, followed by distilled water. They were then dipped in distilled water containing anti-microbial agent for few hours. Vials were dried before use and kept in closed containers.
Step 2: Sterilization of glass-wares:
To avoid the contamination of the eye drops and thereby ocular infection, the glass wares used in the preparation of the ophthalmic formulation were sterilized by autoclaving. The glass vials, filtering assembly, other glass wares etc., were sterilized by moist heat under pressure (151bs) for 15 minutes.
Step 3: Preparing extract of Curcuma longa
Rhizomes of Curcuma longa were procured, identified and processed for the preparation of their aqueous extracts. Curcuma longa rhizomes were powdered, weighed and dissolved in distilled water with constant stirring for 24 hrs. Solution was filtered. Dissloved part was dried and weighed to calculate the solubility.
Step 4: Weighing the extract accurately on a sensitive balance.
Extract of Curcuma longa was weighed accurately using an electronic Mettler balance to be reconstituted in water to obtain 0.05% to 5% w/v solution.
Step 5: Use of double distilled water
Distilled water used for the eye drops was double distilled with the help of a Distillation apparatus.
Step 6: Preparation of solution in laminar hood
The herbal extracts were accurately weighed, poured in a beaker and dissolved in the required volume of autoclaved distilled water under sterile conditions in a laminar hood. A sterile (autoclaved) stirrer was used for mixing the drugs and the solution was stirred occasionally until properly mixed. The beaker was covered with an aluminium foil.
Step 7: Adding of visco elastic substance
Visco elastic substance in the range of 0.1 to 5 % was accurately weighed and dissolved in autoclaved distilled water using autoclaved glass stirrer. It was stored at 4 ° C for 24 hours. To this the herbal extract of Curcuma longa was added and dissolved stirring with autoclaved glass stirrer in a laminar hood. The solution was stirred occasionally until properly mixed. The beaker was covered with an aluminium foil.
Step 8: Sterilization of eye drops using micropore filtration
Micropore filters having diameter 7 mm and size 0.2 urn were used to filter the eye drop solution. Filtration was carried out using an autoclaved Millipore filteration unit in a laminar hood.
Effect of herbal eye drops
Antioxidant nature of herbal extracts was established by monitoring lipid peroxidation product (MDA), gluathione (GSH) levels and antioxidant enzyme activities like superoxide dismutase(SOD), gluthathione peroxidase (GPx), catalase(CAT) and glutathione-S-transferase (GST) in isolated rat lenses exposed to osmotic/oxidative stress.
"'Incorporation of 30 mM galactose in culture medium resulted in significant hydration, osmotic swelling and accumulation of polyols in the lens. Oxidative insult to lens was induced by incubating the lenses in tissue culture medium with either riboflavin (100µM), or hydrogen peroxide (0.2mM) or sodium selenite (100 µM). Effect of these agents on lens clarity as well as on antioxidant biochemical parameters was observed. To study preventive role of the herbal formulations (test compound), the medium was also supplemented with different concentrations of these. Photodocumentation of the lens was achieved and then were analyzed for biochemical parameters.
The activity of herbal ophthalmic formulation was evaluated in vivo, in experimentally induced galactose cataract in rats. The rats were equally divided into control and test groups. Wistar rats (50-70g) of either sex were used for the study and fed with 30 % galactose in diet and water ad libitum to induce galactose cataract.
The rats in the test group were instilled with 1 eye drop of the herbal extract twice a day from the day of the cataractogenic insult and was continued till the end of the experiment. At regular intervals, cataract stages in both the groups were graded according to the classification of Sippel using a slit lamp bio-microscope after dilation of the pupil.
At stage 0 lens is similar to the normal lens; stage 1= faint peripheral opacity; stage 11= irregular peripheral opacity and slight involvement of the lens at the center; stage 111= irregular opacity involving entire lens, stage IV= pronounced opacity readily visible as white spot
Onset and stage wise progression of cataract was recorded for groups. An overall grade point average was calculated to compare the rate of progression in test group with that of control.
For doing so normal eyes were given no points, stage I-one point; stage II-two points; stage III- three points and stage IV-four points. The sum of points in each group was divided by the number of eyes to get opacity index (OI) of that group. The Statistical significance between the two groups was determined using two tailed, unpaired students 't' test and 'p' value less than 0.05 was considered to be significant.
The results of the test as shown in table 1 confirm that instillation of herbal ophthalmic formulation significantly delayed the onset and the progression of galactose induced cataract as compared to control.
The herbal ophthalmic formulation is a synergistic composition.
The present inventions will now be described with reference to the foregoing examples:
Example 1:
0.02 % w/v of aqueous extract Curcuma longa was mixed to 0.25 % w/v of Hydroxy propyl methyl cellulose to obtain the herbal formulation.
Onset and progression of galactose cataract was delayed significantly by instillation of one eye drop two times per day as compared to control. The O.I on 7th day was 0.88 and on 30th day it was 2.68 in comparison to 1 and 4 in control respectively (Table-1)
Example 2:
0.01 % w/v of aqueous extract of Curcuma longa was mixed to 0.25 % w/v of Hydroxy propyl methyl cellulose to obtain the herbal formulation.
Onset and progression of galactose cataract was delayed significantly by instillation of one eye drop two times per day as compared to control. The O.I on 7th day was 0.88 and on 30n day it was 2.94 in comparison to 1 and 4 in control respectively (Table-1)
Example 3:
0.01 % w/v of aqueous extract of Curcuma longa was mixed to 0.25 % w/v of sodium hyaluronate to obtain the herbal formulation.
Example 4:
0.02 % w/v of aqueous extract Curcuma longa was mixed to 0.25 % w/v of polyacrylamide to obtain the herbal formulation.
DOSAGE
One drop twice a day.






WE CLAIM:
1. A herbal ophthalmic formulation of Curcuma longa for delaying the onset and progression of cataract comprising:
0.01 % to 5 % w/v of extract of rhizome of Curcuma longa and 0.1 %- 5 % w/v visco elastic substance and q.s distilled water
2. A herbal ophthalmic formulation as claimed in claim 1 wherein said extract of Curcuma longa is an aqueous extracts.
3. A herbal ophthalmic formulation as claimed in claim 1 wherein said visco elastic substance is selected from Hydroxy propyl methyl cellulose, Sodium Hyaluronate, Chondroitin Sulfate or Polyacrylamide or a mixture thereof.
4. A herbal ophthalmic formulation as claimed in claim 4 wherein said visco elastic substance is Hydroxy propyl methyl cellulose
5. A herbal ophthalmic formulation as claimed in claim 1 wherein said ingredients are mixed in the following proportions:
Curcuma longa - 0.02 % w/v and
visco elastic substance - 0.25 % w/v
6. A herbal ophthalmic formulation as claimed in claim 1 wherein said ingredients are mixed in the following proportions:
Curcuma longa - 0.01 % w/v and
visco elastic substance - 0.25 % w/v
7. A herbal ophthalmic formulation for delaying the onset and progression of cataract substantially as herein described with reference to the foregoing examples.

Documents:

419-del-2002-abstract.pdf

419-del-2002-claims.pdf

419-del-2002-correspondence-others.pdf

419-del-2002-correspondence-po.pdf

419-del-2002-description (complete).pdf

419-del-2002-form-1.pdf

419-del-2002-form-19.pdf

419-del-2002-form-2.pdf

419-del-2002-form-3.pdf

419-del-2002-form-4.pdf

419-del-2002-gpa.pdf


Patent Number 250881
Indian Patent Application Number 419/DEL/2002
PG Journal Number 06/2012
Publication Date 10-Feb-2012
Grant Date 03-Feb-2012
Date of Filing 28-Mar-2002
Name of Patentee ALL INDIA INSTITUTE OF MEDICAL SCIENCES,
Applicant Address ANSARI NAGAR, NEW DELHI-110 029, INDIA
Inventors:
# Inventor's Name Inventor's Address
1 DR. GUPTA SURESH KUMAR DEPARTMENT OF PHARMACOLOGY , ALL INDIA INSTITUTE OF MEDICAL SCIENCES, ANSARI NAGAR, NEW DELHI-110 029, INDIA.
2 DR. JOSHI SUJATA DEPARTMENT OF PHARMACOLOGY , ALL INDIA INSTITUTE OF MEDICAL SCIENCES, ANSARI NAGAR, NEW DELHI-110 029, INDIA.
3 DR. SRIVASTAVA SUSHMA DEPARTMENT OF PHARMACOLOGY , ALL INDIA INSTITUTE OF MEDICAL SCIENCES, ANSARI NAGAR, NEW DELHI-110 029, INDIA.
4 DR. TRIVEDI DEEPA DEPARTMENT OF PHARMACOLOGY , ALL INDIA INSTITUTE OF MEDICAL SCIENCES, ANSARI NAGAR, NEW DELHI-110 029, INDIA.
5 MRS. HALDER DEPARTMENT OF PHARMACOLOGY , ALL INDIA INSTITUTE OF MEDICAL SCIENCES, ANSARI NAGAR, NEW DELHI-110 029, INDIA.
PCT International Classification Number A61K 35/78
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA