Ophthalmic viscoelastic formulations suitable for use in cataract surgery

Abstract

The invention relates to a new ophthalmic viscoelastic formulation suitable for use during or after cataract surgery to reduce intraocular pressure in the operation area and to create a space in the anterior chamber of the eye, as well as to maintain this space.

Description

[0001] DESCRIPTION OPHTHALMIC VISCOELASTIC FORMULATIONS SUITABLE FOR USE IN

[0002] CATARACT SURGERY

[0003] TECHNICAL FIELD

[0004] The invention relates to new ophthalmic viscoelastic formulations suitable for use during or after cataract surgery to reduce intraocular pressure in the operation area and to create a space in the anterior chamber of the eye, as well as to maintain this space.

[0005] In another aspect, the invention relates to ophthalmic viscoelastic formulations with dispersive, cohesive or viscoadaptive properties, suitable for use in cataract surgery.

[0006] In another aspect, the invention relates to methods for obtaining ophthalmic viscoelastic formulations with dispersive, cohesive or viscoadaptive properties, suitable for use in cataract surgery.

[0007] PRIOR ART

[0008] Cataract is an eye disease that causes vision loss due to the loss of transparency of the natural lens in the eye. Cataracts can occur due to many factors such as aging, genetic factors, traumas, infections or long-term drug use. Cataract surgery, on the other hand, is the process of removing the cataract that causes vision loss. During this surgery, the clouded natural lens is surgically removed and replaced with an artificial lens (intraocular lens). This artificial lens allows the patient to see clearly at far or close distances.

[0009] Glaucoma is an eye disease that can cause damage to the optic nerve due to high intraocular pressure. The optic nerve is located at the back of the eye and transfers images from the eye to the brain. High intraocular pressure can damage the optic nerve and cause vision loss. Glaucoma can usually progress without symptoms, which is why it is also called "silent blinder". Usually, vision loss begins as the disease progresses, and usually central vision is affected.

[0010] As is known in the art, the intraocular pressure may increase during or after cataract surgery. In some cases, a glaucoma treatment such as a stent in the front of the eye or a device inserted inside the eye may also be performed to lower intraocular pressure during cataract surgery. These procedures reduce intraocular pressure by regulating the flow of fluid in the eye.

[0011] Eye drops with different mechanisms of action, which are used to reduce intraocular pressure in the technical field of ophthalmology, have some side effects. These effects are mentioned in the following lines:

[0012] Possible side effects of prostaglandin-containing eye drops include mild redness and stinging of the eyes, darkening of the iris, darkening of the pigment of the eyelashes or eyelid skin, and blurred vision. This class of medication is prescribed for use once a day.

[0013] Possible side effects of p-Adrenergic blocker-containing eye drops include difficulty in breathing, slowed heart rate, low blood pressure, impotence, and fatigue. This class of medication may be prescribed for use once or twice a day, depending on the condition.

[0014] Possible side effects of a-Adrenergic blocker-containing eye drops include irregular heart rate, high blood pressure, fatigue, red, itchy or swollen eyes, and dry mouth. This class of medication is usually prescribed for use twice a day, but sometimes it may be prescribed for use three times a day.

[0015] Possible side effects of carbonic anhydrase inhibitor-containing eye drops include a metallic taste, frequent urination, and tingling in the fingers and toes. This class of medication is usually prescribed for use twice a day, but sometimes it may be prescribed for use three times a day.

[0016] Possible side effects of Rho kinase inhibitor-containing eye drops include eye redness and eye discomfort. It can be prescribed for use once daily.

[0017] Possible side effects of miotic and cholinergic agents-containing eye drops include headache, eye pain, smaller pupils, possible blurred or dim vision, and myopia. This class of medication is usually prescribed for use up to four times a day. Due to their potential side effects and the necessity of frequent daily use, these medications are no longer prescribed very often. In the technical field of ophthalmology, the use of ophthalmic viscosurgical devices in cataract surgery is becoming widespread instead of eye drops in the technical field of ophthalmology. In the art, jelly-like substances can be used to reduce intraocular pressure in ophthalmology, and these substances are called ophthalmic viscosurgical devices (abbreviated as OVD). The purpose of using OVD is to protect the structures inside the eye, facilitate surgical procedures and accelerate postoperative recovery. This substance can be used as a gel-like liquid in the front of the eye and acts as a buffer between the tissues of the eye. The OVD also maintains the pressure inside the eye and the shape of the eye.

[0018] Early transient increases in intraocular pressure (abbreviated as IOP) after cataract surgery usually occur as a result of damage to the trabecular meshwork during surgery, free radicals, retrobulbar anesthesia, prostaglandins, inflammatory debris, peripheral anterior synechiae, vitreous in the anterior chamber, developing hyphema, position of the intraocular lens (abbreviated as IOL) and ophthalmic viscosurgical devices (OVD) used. While high-viscosity OVDs are advantageous during surgery, they cause an increase in IOP by causing temporary occlusion in the trabecular meshwork while leaving the eye through the trabecular route after surgery. The postoperative IOP increase usually reaches its peak value at 6-8 hours and decreases to normal values within 24 hours. This condition is usually benign and temporary in normal eyes. However, in cases with atherosclerotic or glaucoma; increased glaucomatous damage to the optic nerve can cause pathologies such as anterior ischemic optic neuropathy and central retinal vein occlusion. In addition, corneal edema and inhibition of wound healing can be seen.

[0019] As a result, it has been determined that OVDs, which are used especially in cataract surgery or other eye surgeries to reduce elevated intraocular pressure values and to maintain the shape of the eye, should be formulated in accordance with the type of surgical operation in which they will be used and to meet the needs of the eye during the operations. It is necessary to develop cohesive, dispersive or viscoadaptive ophthalmic viscoelastic formulations that perform multiple functions at the same time by being used to create a space in the anterior chamber of the eye, as well as to maintain this space during cataract surgery, and also to prevent the increase in intraocular pressure that may occur after the surgical procedure.

[0020] BRIEF DESCRIPTION OF THE INVENTION Especially in cataract surgery, and also in treatment or surgery of other eye diseases, problems of increased intraocular pressure are encountered. In order to prevent this, eye drops containing active ingredients that reduce intraocular pressure are used, however, the technical disadvantages created by these eye drops are known. Therefore, OVDs with different technical mechanisms than eye drops are used. However, the use of OVDs in cases with atherosclerotic or glaucoma, increased glaucomatous damage to the optic nerve can cause pathologies such as anterior ischemic optic neuropathy and central retinal vein occlusion. In addition, it may cause corneal edema and inhibition of wound healing. In order to overcome the aforementioned technical problems and to provide new solutions to the relevant technical field, the inventors propose to formulate OVDs suitable for the surgical operation to be performed for the relevant technical field.

[0021] The primary objective of the present invention is to introduce new ophthalmic viscoelastic formulations suitable for use especially during or after cataract surgeries to reduce intraocular pressure, to create a space in the anterior chamber of the eye, as well as to maintain this space, and also to prevent the increase in intraocular pressure that may occur after surgical operations.

[0022] The primary objective of the present invention is to introduce an ophthalmic viscoelastic formulation having cohesive, dispersive or viscoadaptive properties for use in a surgical operation to be performed.

[0023] Another aspect of the invention is to introduce a method for obtaining ophthalmic viscoelastic formulations having cohesive, dispersive or viscoadaptive properties for use in a surgical operation to be performed.

[0024] DETAILED DESCRIPTION OF THE INVENTION

[0025] In this detailed description, the subject of the invention relates to a new ophthalmic viscoelastic formulation and a method for obtaining said ophthalmic viscoelastic formulations, and is explained only with examples for a better understanding of the subject, which will not create any limiting effect. The ophthalmic viscoelastic formulation subject to the invention contains sodium hyaluronate and at least one active substance which are expected to provide different functions.

[0026] The ophthalmic viscoelastic formulation contains the sodium hyaluronate component to show and provide a skeletal structure for its final formulation. While the inventors of the present invention have provided teachings to the relevant technical field to obtain the formulation of OVDs suitable for the surgical operation and the anatomy of the eye in the relevant technical field, the main ingredient providing said embodiments here is sodium hyaluronate. In order for the final formulation to be at the target zero shear viscosity values, the molecular weight and amount of sodium hyaluronate component in the formulation are of importance.

[0027] In this invention, by osmolality, it is meant the term used to measure the osmotic concentration of the formulation. According to ISO 15798 Ophthalmic Implants, Ophthalmic Viscosurgical Devices standard, the osmomality value is between 200 and 400 mOsm / kg that should be evaluated in finished products. In this invention, the osmolality value is between 300 and 350 mOsm / kg in the final products.

[0028] In this invention, by zero shear viscosity, it is meant the term used to measure the fluidity of the formulation at a very low velocity. Zero shear viscosity is related to the ability of OVDs to maintain anterior chamber space. "Zero shear" is a term used to describe a condition in which there is no fluid movement in the eye. Cohesive OVDs tend to intertwine during zero-shear conditions; this feature helps these types of OVDs to maintain the intraocular space very effectively.

[0029] The ophthalmic viscoelastic formulation of this invention contains sodium hyaluronate at the molecular weights and amounts determined to create a space in the anterior chamber of the eye, as well as to maintain this space, and at least one active substance to reduce intraocular pressure. Said active ingredient is present in the formulations at a value in the range of 0.05% to 10% by weight.

[0030] This invention comprises at least one prostaglandin as an active ingredient. The purpose of comprising prostaglandin as said active ingredient is to increase the outflow of fluid in the eye and help reduce eye pressure. In this invention, there is at least one active ingredient present selected from the group of latanoprost, travoprost, tafluprost, bimatoprost, and latanoprostene bunod as prostaglandin. The formulation contains prostaglandin, preferably at a value between 0.03% to 0.1 %.

[0031] This invention comprises at least one p-Adrenergic blocker as an active ingredient. Said P-Adrenergic blocker reduces fluid production in the eye, allowing eye pressure to be reduced. This invention comprises at least one active ingredient selected from the group of timolol, carteolol, metipranolol, befunolol, levabunolol and betaxolol as p-Adrenergic blockers. The formulations contain the p-Adrenergic blocker preferably at a value between 0.015% to 1%.

[0032] This invention comprises at least one a-Adrenergic blocker as an active ingredient. Said a-Adrenergic blocker is included to reduce the production of the fluid flowing in the eye. This invention comprises at least one active ingredient selected from the group of apraclonidine and brimonidine as an a-adrenergic blocker. The formulations contain the a-Adrenergic blocker preferably at a value between 0.05% to 1 .2%.

[0033] This invention comprises at least one carbonic anhydrase inhibitor as an active ingredient. Said carbonic anhydrase inhibitor is included to reduce fluid production in the eye. The invention comprises at least one active ingredient selected from the group of dorzolamide and brinzolamide as a carbonic anhydrase inhibitor. The formulations contain the carbonic anhydrase preferably at a value between 0.5% to 3%.

[0034] This invention contains at least one miotic or cholinergic agent as an active ingredient. Said miotic or cholinergic agent is included to increase the outflow of fluid in the eye. This invention includes pilocarpine as a miotic or cholinergic agent. The formulations contain the cholinergic or miotic agent preferably at a value between 0.5% to 4% by weight.

[0035] This invention comprises at least one rho kinase inhibitor as an active ingredient. The invention comprises netarsudil as the rho kinase inhibitor. These reduce eye pressure by suppressing rho kinase enzymes responsible for fluid increase. The formulations contain the rho kinase inhibitor to be used preferably at a value in the range of 0.01% to 0.05% by weight. The innovative aspect of the invention is the development of ophthalmic viscoelastic formulations to prevent the increase in intraocular pressure and to protect the eye, especially during and after cataract surgical operations.

[0036] Cohesive ophthalmic viscoelastic formulations: cohesive OVDs show high viscosity and adhere well to each other through intramolecular interactions and are therefore resistant to cleavage. Due to their high molecular weight with long chains, they have high surface tension and a high degree of pseudoplasticity. Therefore, cohesive OVDs are excellent devices to flatten the anterior capsule and create space during capsulorhexis, especially in hyperopic eyes with a flat anterior chamber. Similarly, they can be used to inflate the capsule during the intraocular lens (IOL) implantation process to facilitate a safe insertion of the implant.

[0037] Dispersive ophthalmic viscoelastic formulations: They can coat intraocular structures and better adhere to this region by enveloping them like a layer, due to their lower viscosity and high adhesion ability. Their molecules behave moving freely and have low pseudoplasticity and surface tension, and are formulated with low molecular weight. As a result of these properties, dispersive OVDs remain in the injected medium for a longer duration, better protecting the corneal endothelium and other intraocular tissues

[0038] - Viscoadaptive ophthalmic viscoelastic formulations: They acts differently under various fluid parameters during phaco: they stay together at low flow and act as a cohesive viscoelastic, while at high flow rates they disperse and disperse like a dispersive viscoelastic.

[0039] The three types of OVD features characterized in the invention can be used in all cataract surgeries. OVD with cohesive properties creates volume in the eye due to its high viscosity and cohesive structure. OVDs with said properties do not spread when injected into the eye and accumulate where they are squeezed. OVDs with dispersive properties spread inside the eye and protect the points where they spread in the eye. Since surgical equipments are constantly inserted and removed from the eye, there is a possibility of damage to the tissues. OVDs with dispersive properties are used to minimize or ensure that this damage is not done. Due to its low viscosity, it spreads and adheres to tissues. Both cohesive and dispersive OVDs are used at different stages of surgery. Viscoadaptive, on the other hand, is an OVD showing cohesive and dispersive properties.

[0040] The main embodiment of this invention is the development of ophthalmic viscoelastic formulations having suitable osmolality and zero shear viscosity values depending on the need. Accordingly, the inventors provide the following technical teachings; for the formulation of cohesive ophthalmic viscoelasticity, the osmolality value should be in the range of 300 to 350 mOsm / kg and the zero shear viscosity value should have a value in the range of 50000 to 3000000 mPa.s,

[0041] - for the dispersive ophthalmic viscoelastic formulation, the osmolality value should be in the range of 300 to 350 mOsm / kg and the zero shear viscosity value should have a value in the range of 5000 to 200000 mPa.s,

[0042] - for the viscoadaptive ophthalmic viscoelastic formulation, the osmolality value should be in the range of 300 to 350 mOsm / kg and the zero shear viscosity value should have a value in the range of 25000 to 2000000 mPa.s.

[0043] As mentioned earlier, the ophthalmic viscoelastic formulation subject to the invention is mainly in gel form, and said ophthalmic viscoelastic formulation herein is mainly sodium hyaluronate, which ensures that the gel form is cohesive, dispersive or viscoadaptive. Accordingly, it is critical that the sodium hyaluronate component in the ophthalmic viscoelastic formulation gel form has determined molecular weight and weight ratios. The inventors of the present invention provide the following technical teachings for obtaining the final formulation with determined osmolality and zero shear viscosity values;

[0044] - for obtaining a cohesive ophthalmic viscoelastic formulation, the molecular weight of the sodium hyaluronate component in the formulation should be at a value between 1500 to 4500 kDa and the amount of its presence should be at a value in the range of 1% to 2.5% by weight,

[0045] - for obtaining a dispersive ophthalmic viscoelastic formulation, the molecular weight of the sodium hyaluronate component in the formulation should be at a value between 500 to 1000 kDa and the amount of its presence should be at a value in the range of 2.5% to 3.5% by weight,

[0046] - for obtaining a viscoadaptive ophthalmic viscoelastic formulation, the formulation must contain a sodium hyaluronate component with a molecular weight at a value between 1500 to 4500 kDa and a presence amount at a value in the range of 0.5% to 1 .5% by weight, and a sodium hyaluronate component with a molecular weight at a value between 500 to 1000 kDa and a presence amount at a value in the range of 1% to 2% by weight.

[0047] In the case of an ophthalmic viscoelastic formulation with cohesive, dispersive, or viscoadaptive properties subject to the invention, it comprises a sodium hyaluronate component having a determined amount and molecular weight and at least one active ingredient at a value in the range of 0.05% to 10% by weight. At least one active ingredient in the formulations is used in determined ratios to reduce eye pressure by increasing the outflow of fluid in the eye during or after cataract surgery.

[0048] The ophthalmic viscoelastic formulations subject to the invention are in gel form. As mentioned before, the cohesive, dispersive or viscoadaptive properties of ophthalmic viscoelastic formulations in gel form are due to the presence of sodium hyaluronate in the previously determined molecular weights and presence amounts. As a result, the ophthalmic viscoelastic formulations subject to the invention, even if they have cohesive, dispersive, or viscoadaptive properties, can be obtained in gel form by the same production method. In one aspect, the invention is related to the method for the production of ophthalmic viscoelastic formulations with cohesive, dispersive, or viscoadaptive properties in gel form. The method subject to the invention includes the following process steps;

[0049] - filling the water for injection into the solution preparation vessel,

[0050] - preparation of the first solution by adding salts to the solution tank and dissolving them to form a buffer solution,

[0051] - obtaining the second solution by passing the first solution through the filter

[0052] - adding and mixing at least one active ingredient and sodium hyaluronate having the molecular weight and presence amounts determined for the final formulation expected to be cohesive, dispersive or viscoadaptive to the second solution and obtaining the third solution performing vacuuming processes with the third solution.

[0053] In this invention, at least one of the group of sodium chloride, disodium hydrogen phosphate dihydrate, sodium dihydrogen phosphate dihydrate is used as said salt. It is ensured that the buffer solution prepared by using at least one of this group as a salt has a pH value of 7 to 8 and an osmolality value between 280 to 350 mOsm / kg.

[0054] The second solution is obtained by passing the first solution through a micron sterile filter at a value between 0.1 -0.4.

[0055] The amount of sodium hyaluronate added during the preparation of the third solution is as follows;

[0056] - for obtaining a cohesive ophthalmic viscoelastic formulation, the molecular weight of the sodium hyaluronate component in the formulation is at a value between 1500 to 4500 kDa and the amount of its presence should be at a value in the range of 1% to 2.5% by weight,

[0057] - for obtaining a dispersive ophthalmic viscoelastic formulation, the molecular weight of the sodium hyaluronate component in the formulation is at a value between 500 to 1000 kDa and the amount of its presence should be at a value in the range of 2.5% to 3.5% by weight,

[0058] - for obtaining a viscoadaptive ophthalmic viscoelastic formulation, the formulation has a sodium hyaluronate component with a molecular weight at a value between 1500 to 4500 kDa and a presence amount at a value in the range of 0.5% to 1 .5% by weight, and a sodium hyaluronate component with a molecular weight at a value between 500 to 1000 kDa and a presence amount at a value in the range of 1% to 2% by weight.

[0059] During the preparation of the third solution, at least one active ingredient in the range of 0.05% to 10% by weight is added to the formulation. The reason for the addition at this value is the use of a similar concentration in products on the market such as eye drops, such as eye drops, which lower intraocular pressure.

[0060] The mixing process in the preparation of the third solution is performed with a duration in the range of 10 to 50 hours and a value in the range of 12 to 60 rpm. In this way, a homogeneous mixture can be obtained.

[0061] The vacuuming process of the third solution is preferably performed for a duration of 12 to 72 hours. Owing to the vacuuming process, the bubbles in the mixture can be removed. If bubbles are formed during the mixture and are not removed, it causes technical problems in the injection tool.

[0062] In a preferred embodiment, after vacuuming processes for the third solution,

[0063] - the processes of placing the obtained solution in the injectors and performing plugging operations under vacuum,

[0064] - sterilizing the obtained injectors are performed.

[0065] These sterilization processes are performed until F0:12 is reached, preferably at a value between 120 to 130 °C.

[0066] With the formulations subject to the invention, a new OVD can be obtained by combining the active ingredient that reduces intraocular pressure with sodium hyaluronate compounds with cohesive, dispersive, and viscoelastic properties.

[0067] With the formulations subject to the invention, the technical negativities caused by eye drops, which are determined to have technical disadvantages when used in glaucoma and cataract disorders in the technical field of ophthalmology, have been eliminated.

[0068] With the formulations subject to the invention, the need for the use of additional eye drops after the operations has been eliminated by adding them during surgical operations.

[0069] The scope of protection of the invention is specified in the appended claims and cannot be limited to what is described for illustrative purposes in this detailed description. It is clear that a person skilled in the art can produce similar embodiments in the light of what is explained above, without deviating from the main theme of the invention.

Claims

CLAIMS1. A ophthalmic viscoelastic formulation suitable for use especially during or after cataract surgery to reduce intraocular pressure in the operation area and to create a space in the anterior chamber of the eye, as well as to maintain this space, characterized in that, for obtaining ophthalmic viscoelastic formulation with cohesive properties having a osmolality value in the range of 300 to 350 mOsm / kg and a zero shear viscosity value at a value in the range of 50000 to 3000000 mPa.s, the molecular weight of the sodium hyaluronate component in the formulation is at a value between 1500 to 4500 kDa and the amount of its presence should be at a value in the range of 1 % to 2.5% by weight.

2. A ophthalmic viscoelastic formulation suitable for use especially during or after cataract surgery to reduce intraocular pressure in the operation area and to create a space in the anterior chamber of the eye, as well as to maintain this space, characterized in that, for obtaining ophthalmic viscoelastic formulation with dispersive properties having a osmolality value in the range of 300 to 350 mOsm / kg and a zero shear viscosity value at a value in the range of 5000 to 200000 mPa.s, the molecular weight of the sodium hyaluronate component in the formulation is at a value between 500 to 1000 kDa and the amount of its presence should be at a value in the range of 2.5% to 3.5% by weight.

3. A ophthalmic viscoelastic formulation suitable for use especially during or after cataract surgery to reduce intraocular pressure in the operation area and to create a space in the anterior chamber of the eye, as well as to maintain this space, characterized in that, for obtaining ophthalmic viscoelastic formulation with viscoadaptive properties having a range of 300 to 350 mOsm / kg and a zero shear viscosity value at a value in the range of 25000 to 2000000 mPa.s, it contains a sodium hyaluronate component with a molecular weight at a value between 1500 to 4500 kDa and a presence amount at a value in the range of 0.5% to 1 .5% by weight, and a sodium hyaluronate component with a molecular weight at a value between 500 to 1000 kDa and a presence amount at a value in the range of 1% to 2% by weight.

4. An ophthalmic viscoelastic formulation according to one of the preceding claims, characterized in that it contains at least one active ingredient.

5. An ophthalmic viscoelastic formulation according to claim 4, characterized in that it comprises at least one selected from the group of prostaglandin, p- Adrenergic blocker, a-Adrenergic blocker, carbonic anhydrase inhibitor, and miotic or cholinergic agent as an active ingredient, in combination or all together.

6. An ophthalmic viscoelastic formulation according to one of claim 4-5, characterized in that it comprises at least one active ingredient selected from the group of latanoprost, travoprost, tafluprost, bimatoprost, and latanoprostene bunod as prostaglandin.

7. An ophthalmic viscoelastic formulation according to one of claim 4-6, characterized in that it comprises at least one active ingredient selected from the group of timolol, carteolol, metipranolol, befunolol, levabunolol and betaxolol as p-Adrenergic blockers.

8. An ophthalmic viscoelastic formulation according to one of claim 4-7, characterized in that it comprises at least one active ingredient selected from the group of apraclonidine and brimonidine as a-adrenergic blockers.

9. An ophthalmic viscoelastic formulation according to one of claim 4-8, characterized in that it comprises at least one active ingredient selected from the group of dorzolamide and brinzolamide as a carbonic anhydrase inhibitor.

10. An ophthalmic viscoelastic formulation according to one of claim 4-9, characterized in that it comprises pilocarpine as a miotic or cholinergic agent.11 . An ophthalmic viscoelastic formulation according to any one of the preceding claims, characterized in that said active ingredient is present in the formulation at a value in the range of 0.05% to 10% by weight.

12. A method for the production in gel form of ophthalmic viscoelastic formulations with cohesive, dispersive, or viscoadaptive properties according to one of the preceding claims, characterized in that it comprises the process steps of- filling the water for injection into the solution preparation vessel,- preparation of the first solution by adding salts to the solution tank and dissolving them to form a buffer solution,- obtaining the second solution by passing the first solution through the filter- adding and mixing at least one active ingredient and sodium hyaluronate having the molecular weight and presence amounts determined for the final formulation expected to be cohesive, dispersive or viscoadaptive to the second solution and obtaining the third solution performing vacuuming processes with the third solution.

13. A method according to claim 12, characterized in that in order for said final formulation to have a pH of 7 to 8, at least one of the group of sodium chloride, disodium hydrogen phosphate dihydrate, sodium dihydrogen phosphate dihydrate, is added to water to obtain a buffer solution.

14. A method according to one of claim 12-13, characterized in that, for obtaining a cohesive ophthalmic viscoelastic formulation, the molecular weight of the sodium hyaluronate component in said third solution is at a value between 1500 to 4500 kDa and the amount of its presence is at a value in the range of 1% to 2.5% by weight.

15. A method according to one of claim 12-14, characterized in that, for obtaining a dispersive ophthalmic viscoelastic formulation, the molecular weight of the sodium hyaluronate component in said third solution is at a value between 500 to 1000 kDa and the amount of its presence is at a value in the range of 2.5% to 3.5% by weight.

16. A method according to one of claim 12-15, characterized in that, for obtaining ophthalmic viscoelastic formulation with viscoadaptive properties having a range of 300 to 350 mOsm / kg and a zero shear viscosity value at a value in the range of 25000 to 2000000 mPa.s, the third solution contains a sodium hyaluronatecomponent with a molecular weight at a value between 1500 to 4500 kDa and a presence amount at a value in the range of 0.5% to 1 .5% by weight, and a sodium hyaluronate component with a molecular weight at a value between 500 to 1000 kDa and a presence amount at a value in the range of 1 % to 2% by weight.

17. A method according to claim 13 -16, characterized in that said active ingredient is added to the third solution at value between 0.05% to 10% by weight.

18. A method according to claim 12 -17, characterized in that the mixing process for the preparation of the third solution is performed for a duration in the range of 10 to 50 hours and at a value in the range of 12 to 60 rpm.

19. A method according to claim 12-18, characterized in that the vacuuming process of the third solution is preferably performed for a duration of 12 to 72 hours.

20. A method according to claim 12-19, characterized in that the first solution is passed through sterile filters with a micron pore diameter between 0.1 to 0.4 to obtain said second solution.