RU2233653C2 - Solution and method for preparing gel based on its for formation locomotor stump and elimination of deficiency in orbit tissue - Google Patents

Abstract

FIELD: medicine, ophthalmology.

SUBSTANCE: invention relates to biologically inert gel-liked substances with high percent of water content. The composition of solution is determined by the following equation: P = MG + BC + B + I wherein P means solution; MG means acrylamide, methacrylamide, N-[tris-(hydroxymethyl)methyl]-acrylamide, 2-hydroxyethylmethacrylate, N-hydroxymethylmethacrylamide, N-hydroxymethylacrylamide, N,N'-methylene-bis-acrylamide, N,N'-1,2-dihydroxyethyl-bis-acrylamide, polyethylene glycol diacrylate, or their mixture; ВС means glycerol, sucrose, dimethylformamide, dimethylsulfoxide, polyvinyl alcohol, ethylene glycol, diethylene glycol, triethylene glycol, or their mixture; B means water; I means ammonium persulfate, potassium persulfate, methylene blue, fluorescein, N,N,N',N'-tetramethylethylenediamine, hydrogen peroxide, N,N-dimethylaminopyridine, triethylamine, acetone, or their mixture. The percent content of each component in solution (mass/volume - for solid substances or volume/volume - for liquid substances): 1% ≤ MG ≤ 40%; ВС is up to 99%; В is up to 99%. И is up to 70% for preparing gels by method of photo- and chemically initiated polymerization for elimination in deficiency of orbit tissues and formation of locomotor stump in evisceration, enucleation and evisceroenucleation. Method involves carrying out polymerization of forms with solution (Р) in air or sealed container in oxygen-free inert atmosphere and controlled moisture and container are filled with one of the following gases: N₂, Ar, CO₂. Method involves using photoinitiated polymerization and chemically initiated polymerization and ready articles made of gel are sterilized by γ-radiation. Invention provides realization of indicated designation.

EFFECT: improved preparing method, valuable medicinal properties of gel.

7 cl, 6 ex

Description

The invention relates to the field of ophthalmology and relates to biologically inert gel-like substances with a high percentage of water.

The invention also relates to the technology of manufacturing implants to eliminate the deficiency of orbit tissue and the formation of the musculoskeletal stump during eviscerisation, enucleation and eviscero-enucleation, as well as a gel-like substance to eliminate deficiency of orbit tissue.

State of the art

Known publications on the formation of the musculoskeletal stump with implantation of a liner made of an elastic shell filled with a hydrogel based on crosslinked polyhydroxyethyl methacrylate with a water content of 38 to 99.9 wt.%, Having a quasi-elastic structure (patent 2055544, RF)

A negative property of it is the loss of liner volume due to the infusion of water through the silicone shell, and therefore, a decrease in the function of the musculoskeletal stump.

There are publications on the formation of the musculoskeletal stump using implantation of a liner made of a hydrogel with a high percentage of water (Thesis for the degree of Doctor of Medical Sciences D.V.Davydova, Moscow, 2000). The specified liner in the distant period has the same negative property as the gel-like substance "Interfal".

The essence of the invention lies in the fact that there are solutions and methods for preparing gels based on them to eliminate the deficiency of orbital tissues and the formation of the musculoskeletal stump during evisceration, enucleation, eviscero-nucleation.

To prepare the gels, a solution of the composition P = MG + BC + B + B + I is used, where P is the solution; MG - acrylamide, methacrylamide, N- {tris (hydroxymethyl) methyl} -acrylamide, 2-hydroxyethylmethacrylate, N-hydroxymethylmethacrylamide, N-hydroxymethylacrylamide, N, N'-methylenebis-acrylamide, N, N'-1,2- dihydroxyethyl bisacrylamide, polyethylene glycol diacrylate or a mixture thereof; BC - glycerin, sucrose, dimethyl foramide, dimethyl sulfoxide, polyvinyl alcohol, ethylene glycol, diethylene glycol, triethylene glycol or a mixture thereof; In - water; And - ammonium persulfate, potassium persulfate, methylene blue, fluorescein, N, N, N ', N'-tetramethylethylenediamine, hydrogen peroxide, N, N-dimethylaminopyridine, triethylamine, acetone or a mixture thereof, the percentage of each component in solution (mass / volume - for solids or volume / volume - for liquid substances): 1% <MG <40%; Sun up to 99%; In up to 99%; And up to 70%.

It is proposed to use the above solution (P) for the manufacture of gels by the method of photo- and chemically initiated polymerization in order to form a musculoskeletal stump during evisceration, enucleation, eviscero enucleation, as well as a gel-like substance to eliminate the deficiency of orbit tissues.

In the claimed solution for the manufacture of implants and gel substances, it is proposed to use the following components:

- Monomers for gel formation (MG).

Various combinations of acrylamide, methacrylamide, N- {tris (hydroxymethyl) methyl} acrylamide, 2-hydroxyethyl methacrylate, N-hydroxymethyl methacrylamide, N-hydroxymethyl acrylamide, N, N'-methylenebisacrylamide, N, N'-1,2-dihydroxy , polyethylene glycol diacrylate.

In this case, the total monomer content in the solution lies in the range of 1-40% (mass / volume).

Various combinations and ratios of monomers make it possible to obtain hydrogels with a wide range of mechanical properties that can be used for the manufacture of products for various purposes.

- The environment for photoinduced polymerization (BC and B).

As a gelation medium, glycerin, dimethylforamide, dimethyl sulfoxide, ethylene glycol, diethylene glycol, triethylene glycol or a mixture thereof, or water-glycerol solutions, solutions of polyvinyl alcohol in water, solutions of sucrose in water, solutions of dimethylformamide in water, dimethyl sulfide solutions are proposed. The content of a high-boiling water-soluble compound (BC) is up to 99% (volume / volume - for liquid or mass / volume - for solid), and water (B) up to 99% (volume / volume).

- Initiators for chemical and photoinduced polymerization (I).

For the chemical initiation of polymerization, we propose the use of water-soluble polymerization initiators and promoters. Namely: ammonium persulfate, potassium persulfate, hydrogen peroxide, ferrous salts, N, N, N ’, N’-tetramethylethylenediamine, triethylamine or other water-soluble polymerization initiators and promoters. N, N-dimethylaminopyridine, acetone, methylene blue, fluorescein or other photoinitiators are used to initiate the polymerization.

Various combinations of the components of the solutions make it possible to obtain hydrogels with various properties, namely:

a) hydrogels, acquiring the shape of the shell after it is filled;

b) hydrogels, drying to a constant mass, changing the volume by more than 20 times and restoring the original form and volume in water or physiological saline;

c) hydrogels that retain their shape under significant mechanical stresses (tensile, shear, torsion, etc.).

These gels can be used to eliminate deficiency of orbit tissue (a) and for the formation of the musculoskeletal stump (b, c).

The manufacturing technology of implants and gel substances from the proposed solutions by photo- and chemically induced polymerization includes the following steps:

- Preparation of solutions and forms;

- Initiation of polymerization;

- washing;

- Sterilization.

When preparing solutions, the components are mixed in strict proportion, degassed and poured into the form of the desired configuration. The photoinitiation of the polymerization process is carried out by ultraviolet (λ≥254 nm) or visible light in air or in an inert gas atmosphere.

Chemical initiation is carried out in air or in an inert gas atmosphere in the presence of chemical initiators. Nitrogen, argon or carbon dioxide are used as an inert gas in photo- or chemically initiated polymerization. The resulting hydrogels are washed in distilled water at 25 ° C for ≥12 hours.

The gel substances used to eliminate the deficiency of the tissues of the orbit, after washing, are sterilized by γ-radiation and stored in a sterilized container.

Gel liners that swell in an aqueous medium and are used to form the musculoskeletal stump after washing, are dried at 25 ° C to constant weight, sterilized by γ-radiation and stored in a sterilized packaging.

Gel inserts for direct implantation in order to form a musculoskeletal stump after washing are sterilized by γ-radiation and stored in physiological saline.

Further, the essence of the invention is disclosed in separate examples, which should not be considered by an expert as limiting the claims of the invention.

Examples

Example 1. The manufacture of gel substances to eliminate the deficiency of orbit tissue.

To a solution of acrylamide and N, N’-methylenebisacrylamide in water (150 μl, 40% (m / v), 19: 1) distilled water (382.5 μl) and glycerin (967.5 μl) are added. The mixture is thoroughly mixed and polymerized under UV radiation (λ = 312 nm) at 50 ° C for 30 minutes. The resulting gel was placed in distilled water (100 ml) and left for 12 hours at 25 ° C. Then the water is drained and the gel is washed with water (100 ml × 3). The washed gel is sterilized under the influence of γ-radiation and is used to eliminate deficiency of orbit tissues.

In this example, for gelation, a solution was used that included the following components: MG — acrylamide + N, N’-methylene bisacrylamide, BC — glycerol, B — water.

Example 2. The manufacture of gel implants swelling in the aquatic environment.

The method of obtaining similar to example 1.

A solution of acrylamide and N, N’-methylenebisacrylamide in water (187.5 μl, 40% (m / v), 19: 1) is taken, distilled water (345 μl) and glycerin (967.5 μl) are added.

The polymerization mixture is poured into the mold of the desired configuration. After polymerization, the obtained hydrogel is washed, dried at 25 ° C to constant mass, sterilized by γ-radiation and used to form the musculoskeletal stump.

In this example, for gelation, a solution was used that included the following components: MG — acrylamide + N, N’-methylene bisacrylamide, BC — glycerol, B — water.

Example 3. The manufacture of a gel liner for direct implantation.

The method of obtaining analogously to example 1.

A solution of acrylamide and N, N’-methylenebisacrylamide in water (375 μl, 40% (m / v), 19: 1) is taken, distilled water (157.5 μl) and glycerin (967.5 μl) are added. The polymerization mixture is poured into the mold of the desired configuration. After polymerization and a series of washes, the finished product is sterilized under the influence of γ-radiation, placed in physiological saline and stored until use.

In this example, for gelation, a solution was used that included the following components: MG — acrylamide + N, N’-methylene bisacrylamide, BC — glycerol, B — water.

Example 4. The technique of the operation to form the musculoskeletal stump during enucleation using a gel insert.

After processing the surgical field and anesthesia on the limb, the conjunctiva and tenon membrane are separated. Tendons of the external rectus muscles are taken to the provisional sutures and separated from the eyeball. The optic nerve is cut with scissors and the eyeball is removed. The proposed insert is implanted in the orbit tissue. Tendons of the external muscles are sutured to the "cap" of the liner. Purse-string sutures are placed on the tenon shell and conjunctiva. The operation is completed by applying a tight pressure bandage.

Patient M., 23 years old, received a left eye injury, after which uncompensated glaucoma developed. After 3 antiglaucomatous operations, the eye went on a subatrophy and there was a threat of damage to the paired eye. The consultation of doctors decided to remove the affected eye with implantation of the proposed insert according to the method described above.

On December 21, 2000 enucleation was performed. After 1 month, an individual cosmetic prosthesis was selected. The stump mobility was equal: outward 32.9 degrees, inward 31 degrees, up 27.63 degrees and down 30.3 degrees. After the manufacture of the cosmetic prosthesis, the cosmetic defect was completely eliminated.

Example 5. The technique of the operation on the formation of the musculoskeletal stump during evisceration using a swelling gel implant.

After processing the surgical field and in the lower external quadrant, the conjunctiva of the tenon membrane and sclera are cut in length of 7 mm. The contents of the scleral capsule are removed into which a lyophilized gel insert of 5-6 mm diameter is implanted. Two sutures are placed on the scleral wound. Using a syringe and cannula, 5 cm ^{3 of} physiological saline are injected into the scleral cavity. The operation is completed by suturing the tenon membrane and conjunctiva.

Patient K., aged 21, received a criminal injury to his right eye. Moved 5 anti-glaucomatous operations without effect. The eye was blind, but continued to grow in size. Given that the injured eye increased by 1/3 compared with normal, the consultation of doctors decided to conduct evisceration according to the above method. The operation was performed on January 11, 2000. A month after the operation, a cosmetic individual prosthesis was selected. The mobility of the musculoskeletal stump was: outward 34.7 degrees, inward 32.5 degrees, up 30.2 degrees and down 32.6 degrees. In everyday life, none of relatives and friends could distinguish a cosmetic prosthesis and its movements from a normal eye.

Example 6. The method of using a gel-like substance to eliminate the deficiency of orbit tissue.

After treating the skin of the eyelids, in the center of localization of the deficiency of the tissues of the orbit, an 0.5% solution of novocaine is injected in the amount necessary to eliminate tissue deficiency.

If necessary, make several such injections. Having received the necessary cosmetic effect, the injection is performed with a cosmetic prosthesis. By changing the syringe, but without removing the needle, the required amount of gel-like substance is introduced from the hydrogel. The operation is completed with a light massage of the injection site.

Patient N. 35 years. 10 years ago, the right eye was removed without implantation of the insert. As a result, the cosmetic prosthesis “sunk” deep into orbit.

On February 15, 2000, the patient underwent surgery to eliminate the deficiency of orbit tissue with the introduction of the proposed gel-like substance from a hydrogel.

As a result, the cosmetic defect was completely eliminated and the patient again felt like an equal member of society.

Claims (7)

1. A solution of the composition P = MG + BC + B + I, where P is the solution; MG - acrylamide, methacrylamide, N- {tris (hydroxymethyl) methyl} -acrylamide, 2-hydroxy-ethyl methacrylate, N-hydroxymethyl methacrylamide, N-hydroxymethyl acrylamide, N, N'-methylene bisacrylamide, N, N'-1,2-dihydroxy-ethylamide polyethylene glycol diacrylate or a mixture thereof; BC - glycerol, sucrose, dimethylformamide, dimethyl sulfoxide, polyvinyl alcohol, ethylene glycol, diethylene glycol, triethylene glycol or a mixture thereof; In - water; And - ammonium persulfate, potassium persulfate, methylene blue, fluorescein; N, N, N ', N'-tetramethylethylenediamine, hydrogen peroxide, N, N-dimethylaminopyridine, triethylamine, acetone or a mixture thereof, the percentage of each component in solution (mass: volume for solids or volume: volume for liquid substances): 1% ≤MG ≤40%; Sun up to 99%; In up to 99%; And up to 70%. 2. The method of preparing a gel based on solution P according to claim 1 to eliminate the deficiency of orbit tissue and the formation of the musculoskeletal stump, including the polymerization of the form with this solution. 3. The method according to claim 2, in which the form with the solution P is polymerized in air or in an airtight container in an oxygen-free inert atmosphere. 4. The method according to claim 2, in which the container is filled with one of the following gases: N ₂ , Ar, CO ₂ . 5. The method according to claim 2, in which photoinitiated polymerization is used. 6. The method according to claim 2, in which chemically initiated polymerization is used. 7. The method according to claim 2, in which the finished gel products are sterilized with γ-radiation.