Title of Invention	"AN OPTHALMIC COMPOSITION"
Abstract	Accordingly the invention provides a novel composition comprising an effective amount of adrenergic agonist together with ophthamically compatible carrier. The adrenergic agonist is phenylephrine hydrochloride. The carrier may be such as benzalkonium chloride. The amount of phenyl ophrine hydrochloride ranges from 5 mg to 500 mg, preferably 10 mg to 200 mg and most preferably 25 mg. -The amount of carrier may vary proportionately with the amount of agonist used. It may range from 0.1 mg to 10 mg.

Title of Invention

"AN OPTHALMIC COMPOSITION"

Abstract

Accordingly the invention provides a novel composition comprising an effective amount of adrenergic agonist together with ophthamically compatible carrier. The adrenergic agonist is phenylephrine hydrochloride. The carrier may be such as benzalkonium chloride. The amount of phenyl ophrine hydrochloride ranges from 5 mg to 500 mg, preferably 10 mg to 200 mg and most preferably 25 mg. -The amount of carrier may vary proportionately with the amount of agonist used. It may range from 0.1 mg to 10 mg.

Full Text	FIELD OF THE INVENTION The present invention provides an ophthalmic composition for relief of intra ocular pressure and relaxation of ciliary muscles. BACKGROUND OF THE INVENTION The human vision is controlled by a complex apparatus located with the socket of the eyeball. The eye primarily consist of a transparent crystalline lens which is located immediately behind the iris. It is composed of fibers that emerge from the epithelium of the iris. The lens is elastic in nature and is easily adapted to contract and relax as required and focus on an object. Slender strong suspensary ligaments are attached to the lens at one end and circular ciliary ligaments or body around the inside of the eye hold the lens in place. The ciliary body contains ciliary muscles which assist in contraction and relaxation of the lens. When the eye is viewing an object, the ciliary muscles within the ciliary body pull the suspensary logaments which in turn pulls the lens causing it to focus on the light emerging from the object. The rays from the object fall on the retina and eventually an inverted image of the object is obtained on the retina. The image formed is converted into electrical impulses and transmitted to the brain, where the image is translated and perceived in upright position. The adjustment of the lens shape to focus at various distances is referred to as "accommodation" or "amplitude of accommodation". The amplitude of accommodation of an eye is the maximum amount that the eye's crystalline lens can accommodate. This amount is very high when young and decreases with age. Continued strain on the ciliary muscles resulting from focus on a singular object such as a computer could cause great strain to the ciliary muscles and lead to other complications. In myopia the image is formed in front of the retina and not on the retina subjecting the lens to greater amplitudes of accommodation. In myopia it is found that the ciliary muscles undergo a fixed contraction for a longer period making the crystalline lens thicker. Continues use of computer and continuous strain on the ciliary muscles impairs its efficiency and also impairs the eye's hemodynamics. Currently use of lenses is one of the solutions to solve the problem of myopia. Use of lenses enables the light rays emerging from the object to focus clearly on the retina. However, it does not improve or restore the efficiency of the ciliary muscles or its hemodynamics. To remedy the above problems in the art, the present invention provides a novel ophthalmic composition. DESCRIPTION OF THE INVENTION Accordingly, the invention provides a novel composition comprising an effective amount of adrenergic agonist together with ophthamically compatible carrier. The adrenergic agonist is phenylephrine hydrochloride. The carrier may be such as benzalkonium chloride. The amount of phenyl ophrine hydrochloride ranges from 5 mg to 500 mg, preferably 10 mg to 200 mg and most preferably 25 mg. The amount of carrier may vary proportionately with the amount of agonist used. It may range from 0.1 mg to 10 mg. The composition of the invention is useful in relieving intra ocular pressure that accumulates within the ciliary body. The composition when applied relaxes the ciliary muscles. The inventors have surprisingly found that phenylephrine hydrochloride decreases elevated intra-ocular pressure. It is selective for the alpha 1-adrenoreceptor-mediated phosphoinositide hydrolysis system. This selectivity results in no mydriasis and absence of vasoconstriction in the micro-vessels in the ciliary body. As a result the intra-ocular pressure built up on account of continuous stress by focusing on a singular object is released, and thus relaxing the ciliary muscles. To achieve the above effect, it is necessary to contact the composition with the surface of the eye during the period of strain, preferably three times a day. If the administration is continued throughout the entire period of the stress, the subject may potentially be relieved of the use of lenses. Thus, it is a surprising finding of the inventors that the composition when contacted with the surface of the eye reaches the ciliary muscles and relieves the accumulated strain. However, since the strain continues for a period, it is important to use the composition during the entire period of the strain. The invention is now illustrated by the following examples which are only meant for the purpose of illustration and not meant to restrict the scope of the invention in any manner. EXAMPLES: Example 1: Preparation of composition A composition as per the principles of the invention was prepared comprising 25mg phenylephrine hydrochloride and 0.1 mg benzalkonium chloride per 1 ml. The composition was formulated into an appropriate dosage form as a solution for further use. Example 2: Evaluation of composition In order to evaluate the impacts of sympathic VNS on distant accommodation function of eyes, 28 patients (55 eyes) suffering from myopia were subjected to the injection of sympathicomimetic agent - Irifrin 2,5%. Irifrin 2,5% represents alpha-adrenergic agonist and contains 25mg phenylephrine hydrochloride and 0,1 mg benzalkonium chloride per 1 ml; it is easily permeable solution into the eye tissues and does not exert systemic activity. The medication was approved by the Pharmaceutical Committee of the Health Department of Russia 12.07.2001 (registration certificate P N° 013268/01-2001 of 02.08.2001 y.) and it was administered in the form of installations bid/day (in the evening and 30 minutes before sleep) for 10-12 days. Treatment efficiency was evaluated by visometry results, subjective assessment of refraction and by measurement of accommodation function parameters: close and distant points of clear vision, absolute and relative volumes of accommodation. In total, medication receipt contributed to authentic (p eye and consequently, AAV increased. However, treatment resultes varied depending on the VNS tone of patients (see table 1). Table 1. Dynamic changes in refraction and accommodation values in patients with myopia after treatment depending on VNS tone Table 1 demonstrates that due to Irifrin 2,5% therapy patients with normotony and vagotony experienced statistically significant (p>0,05) weakening of myopic refraction, elevation of RRA and of AAV owing to PR shift away from eye. However, authentic discrepancies were not observed in a group of patients with sympathicotony (p>0,05). Obviously, the substantial refraction and accommodation effect of irifrin observed in normotonic and vagotonic patients might be attributed to the stimulation of sympathetically innervated portion of ciliary muscle and to the realization of distant accommodation mechanisms. Similar effects were not obtained in sympathicotonic patients during current study as the sympathetic portion of ciliary muscle, presumably, appeared activated due to elevated general tone of vegetative nervous system and further stimulation of ciliary muscle by Irifrin 2,5% failed to lead to anticipated accommodation response. Consequently, VNS tone of myopia patients should be necessarily taken into account prior to Irifrin administration. Thus, gained results prejudice the conventional point of view regarding the responsibility of accommodation "spasm" in the advent of myopia. It seems most likely that evolvement of pre-school short-sightedness is associated with the origin of peculiar "functional paresis" of accommodation but not with the realization of distant accommodation. Above mechanisms are pronounced at a greater extent in vago- and normotonic patients experiencing excessive visual load on parasympathetic portion of ciliary muscle not only at school but at home (working with computer and so on) as well i.e. in case of intent staring at objects located at finite distance. CONCLUSIONS: 1. VNS tone of patients take effects on functional state of accommodation apparatus of eye by way of influencing main parameters of close (RRA) and distant (the farthest point of clear vision) accommodation function. 2. State of accommodation function in school pupils with mild and moderate myopia proved to be closer to the "functional paresis" of distant accommodation rather than to the short-distance accommodation "spasm". 3. "Functional paresis" of accommodation in school pupils with mild and moderate myopia was founded to develop, mostly, due to decrease in the tone of sympathetic VNS. 4. Refraction effect induced by influences of adrenergic agonist - Irifrin 2,5% is associated with the weakening of myopic refraction and with estrangement of the farthest point of clear vision, thereby, corroborating the existence of distant accommodation controlled by sympathetic VNS. 5. Refraction and accommodation effect of adrenergic agonist - Irifrin 2,5% appeared to be more significant in patients with relative deficit of sympathetic reactions i.e. in normotonic and vagotonic patients. WE CLAIM: 1. An ophthalmic composition comprising an effective amount of an adrenergic agonist together with an ophthalmically compatible carrier, wherein the composition is useful for relieving ciliary stress. 2. A composition is claimed in claim 1, wherein the adrenergic agonist is phenylephrine hydrochloride. 3. A composition is claimed in claim 1, wherein the carrier is benzalkonium chloride. 4. A composition is claimed in claim 1, wherein the amount of phenylephrine hydrochloride is 5-500 mg. 5. A composition is claimed in claim 1, wherein the amount of phenylephrine hydrochloride is 25 mg. 6. A composition is claimed in claim 1, wherein the amount of benzalkonium chloride is 0.1 mg to 10 mg. 7. A use of an ophthalmic composition comprising an adrenergic agonist together with an ophthalmically compatible carrier for relaxation of ciliary muscles. 8. A use as claimed in claim 7, wherein the adrenergic agonist is phenylephrine hydrochloride in the amount of 5-500 mg. 9. A use as claimed in claim 7, wherein the carrier is benzalkonium chloride in an amount of 0.1 mg to 10 mg. 10. An ophthalmic composition and a use, substantially as hereindescribed in the foregoing examples.

Full Text

FIELD OF THE INVENTION
The present invention provides an ophthalmic composition for relief of intra ocular pressure and relaxation of ciliary muscles.
BACKGROUND OF THE INVENTION
The human vision is controlled by a complex apparatus located with the socket of the eyeball. The eye primarily consist of a transparent crystalline lens which is located immediately behind the iris. It is composed of fibers that emerge from the epithelium of the iris. The lens is elastic in nature and is easily adapted to contract and relax as required and focus on an object. Slender strong suspensary ligaments are attached to the lens at one end and circular ciliary ligaments or body around the inside of the eye hold the lens in place. The ciliary body contains ciliary muscles which assist in contraction and relaxation of the lens.
When the eye is viewing an object, the ciliary muscles within the ciliary body pull the suspensary logaments which in turn pulls the lens causing it to focus on the light emerging from the object. The rays from the object fall on the retina and eventually an inverted image of the object is obtained on the retina. The image formed is converted into electrical impulses and transmitted to the brain, where the image is translated and perceived in upright position.
The adjustment of the lens shape to focus at various distances is referred to as "accommodation" or "amplitude of accommodation". The amplitude of accommodation of an eye is the maximum amount that the eye's crystalline lens
can accommodate. This amount is very high when young and decreases with age. Continued strain on the ciliary muscles resulting from focus on a singular object such as a computer could cause great strain to the ciliary muscles and lead to other complications.
In myopia the image is formed in front of the retina and not on the retina subjecting the lens to greater amplitudes of accommodation. In myopia it is found that the ciliary muscles undergo a fixed contraction for a longer period making the crystalline lens thicker. Continues use of computer and continuous strain on the ciliary muscles impairs its efficiency and also impairs the eye's hemodynamics.
Currently use of lenses is one of the solutions to solve the problem of myopia. Use of lenses enables the light rays emerging from the object to focus clearly on the retina. However, it does not improve or restore the efficiency of the ciliary muscles or its hemodynamics.
To remedy the above problems in the art, the present invention provides a novel ophthalmic composition.
DESCRIPTION OF THE INVENTION
Accordingly, the invention provides a novel composition comprising an effective amount of adrenergic agonist together with ophthamically compatible carrier. The adrenergic agonist is phenylephrine hydrochloride. The carrier may be such as benzalkonium chloride. The amount of phenyl ophrine hydrochloride ranges from 5 mg to 500 mg, preferably 10 mg to 200 mg and most preferably 25 mg.
The amount of carrier may vary proportionately with the amount of agonist used. It may range from 0.1 mg to 10 mg.
The composition of the invention is useful in relieving intra ocular pressure that accumulates within the ciliary body. The composition when applied relaxes the ciliary muscles. The inventors have surprisingly found that phenylephrine hydrochloride decreases elevated intra-ocular pressure. It is selective for the alpha 1-adrenoreceptor-mediated phosphoinositide hydrolysis system. This selectivity results in no mydriasis and absence of vasoconstriction in the micro-vessels in the ciliary body. As a result the intra-ocular pressure built up on account of continuous stress by focusing on a singular object is released, and thus relaxing the ciliary muscles.
To achieve the above effect, it is necessary to contact the composition with the surface of the eye during the period of strain, preferably three times a day. If the administration is continued throughout the entire period of the stress, the subject may potentially be relieved of the use of lenses.
Thus, it is a surprising finding of the inventors that the composition when contacted with the surface of the eye reaches the ciliary muscles and relieves the accumulated strain. However, since the strain continues for a period, it is important to use the composition during the entire period of the strain.
The invention is now illustrated by the following examples which are only meant for the purpose of illustration and not meant to restrict the scope of the invention in any manner.
EXAMPLES:
Example 1: Preparation of composition
A composition as per the principles of the invention was prepared comprising 25mg phenylephrine hydrochloride and 0.1 mg benzalkonium chloride per 1 ml. The composition was formulated into an appropriate dosage form as a solution for further use.
Example 2: Evaluation of composition
In order to evaluate the impacts of sympathic VNS on distant accommodation function of eyes, 28 patients (55 eyes) suffering from myopia were subjected to the injection of sympathicomimetic agent - Irifrin 2,5%. Irifrin 2,5% represents alpha-adrenergic agonist and contains 25mg phenylephrine hydrochloride and 0,1 mg benzalkonium chloride per 1 ml; it is easily permeable solution into the eye tissues and does not exert systemic activity. The medication was approved by the Pharmaceutical Committee of the Health Department of Russia 12.07.2001 (registration certificate P N° 013268/01-2001 of 02.08.2001 y.) and it was administered in the form of installations bid/day (in the evening and 30 minutes before sleep) for 10-12 days. Treatment efficiency was evaluated by visometry results, subjective assessment of refraction and by measurement of accommodation function parameters: close and distant points of clear vision, absolute and relative volumes of accommodation.
In total, medication receipt contributed to authentic (p eye and consequently, AAV increased. However, treatment resultes varied depending on the VNS tone of patients (see table 1).
Table 1. Dynamic changes in refraction and accommodation values in patients with myopia after treatment depending on VNS tone

Table 1 demonstrates that due to Irifrin 2,5% therapy patients with normotony and vagotony experienced statistically significant (p>0,05) weakening of myopic refraction, elevation of RRA and of AAV owing to PR shift away from eye. However, authentic discrepancies were not observed in a group of patients with sympathicotony (p>0,05).
Obviously, the substantial refraction and accommodation effect of irifrin observed in normotonic and vagotonic patients might be attributed to the stimulation of sympathetically innervated portion of ciliary muscle and to the realization of distant accommodation mechanisms. Similar effects were not obtained in sympathicotonic patients during current study as the sympathetic portion of ciliary muscle, presumably, appeared activated due to elevated general tone of vegetative nervous system and further stimulation of ciliary muscle by Irifrin 2,5% failed to lead to anticipated accommodation response. Consequently, VNS tone of myopia patients should be necessarily taken into account prior to Irifrin administration.
Thus, gained results prejudice the conventional point of view regarding the responsibility of accommodation "spasm" in the advent of myopia. It seems most likely that evolvement of pre-school short-sightedness is associated with the origin of peculiar "functional paresis" of accommodation but not with the realization of distant accommodation. Above mechanisms are pronounced at a greater extent in vago- and normotonic patients experiencing excessive visual load on parasympathetic portion of ciliary muscle not only at school but at home (working with computer and so on) as well i.e. in case of intent staring at objects located at finite distance.
CONCLUSIONS:
1. VNS tone of patients take effects on functional state of accommodation
apparatus of eye by way of influencing main parameters of close (RRA)
and distant (the farthest point of clear vision) accommodation function.
2. State of accommodation function in school pupils with mild and moderate
myopia proved to be closer to the "functional paresis" of distant

accommodation rather than to the short-distance accommodation "spasm".
3. "Functional paresis" of accommodation in school pupils with mild and
moderate myopia was founded to develop, mostly, due to decrease in the
tone of sympathetic VNS.
4. Refraction effect induced by influences of adrenergic agonist - Irifrin 2,5%
is associated with the weakening of myopic refraction and with
estrangement of the farthest point of clear vision, thereby, corroborating
the existence of distant accommodation controlled by sympathetic VNS.
5. Refraction and accommodation effect of adrenergic agonist - Irifrin 2,5%
appeared to be more significant in patients with relative deficit of
sympathetic reactions i.e. in normotonic and vagotonic patients.

WE CLAIM:
1. An ophthalmic composition comprising an effective amount of an
adrenergic agonist together with an ophthalmically compatible carrier, wherein
the composition is useful for relieving ciliary stress.
2. A composition is claimed in claim 1, wherein the adrenergic agonist is
phenylephrine hydrochloride.
3. A composition is claimed in claim 1, wherein the carrier is benzalkonium
chloride.
4. A composition is claimed in claim 1, wherein the amount of
phenylephrine hydrochloride is 5-500 mg.
5. A composition is claimed in claim 1, wherein the amount of
phenylephrine hydrochloride is 25 mg.
6. A composition is claimed in claim 1, wherein the amount of benzalkonium
chloride is 0.1 mg to 10 mg.
7. A use of an ophthalmic composition comprising an adrenergic agonist
together with an ophthalmically compatible carrier for relaxation of ciliary
muscles.
8. A use as claimed in claim 7, wherein the adrenergic agonist is
phenylephrine hydrochloride in the amount of 5-500 mg.
9. A use as claimed in claim 7, wherein the carrier is benzalkonium chloride
in an amount of 0.1 mg to 10 mg.
10. An ophthalmic composition and a use, substantially as hereindescribed in
the foregoing examples.

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Patent Number

269091

Indian Patent Application Number

42/DEL/2007

PG Journal Number

40/2015

Publication Date

02-Oct-2015

Grant Date

30-Sep-2015

Date of Filing

05-Jan-2007

Name of Patentee

SENTISS PHARMA PRIVATE LIMITED

Applicant Address

212, ASHIRWAD COMMERCIAL COMPLEX, D-1, GREEN PARK, NEW DELHI 110016.

Inventors:

#	Inventor's Name	Inventor's Address
1	ALEXEI MIKHAILOVICH KOLODKIN	PROMED EXPORTS PVT. LTD. SHOSSE ENTUSIASTOV, 7, MOSCOW 111024, RUSSIA
2	DMITRY STANISLAVOVICH SOVETKIN	PROMED EXPORTS PVT. LTD., SHOSSE ENTUSIASTOV, 7, MOSCOW 111024, RUSSIA.
3	CHITRA ARVIND	208, ASHIRWAD COMM. COMPLEX, D-1, GREEN PARK, NEW DELHI 110016, INDIA.
4	DEEPAK BAHRI	208, ASHIRWAD COMM. COMPLEX, D-1, GREEN PARK, NEW DELHI 110016, INDIA.

PCT International Classification Number

A61K9/08; A61K9/00; A61K31/4523

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA