RU2314793C2 - Method for producing ophthalmic films - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves preparing aqueous sodium alginate and calcium gluconate solution taken in the following proportion: sodium alginate 73% and calcium gluconate 27%. The prepared ingredients mixture is poured into trays as 1 mm thick layer. Sectioning lattices are inserted into the trays corresponding to given dimensions of (10x7 mm) of oval shape. The product is exposed to simple convection drying during 8 h. 0.1 mm thick films of 10x7 mm are obtained at the end of the process.

EFFECT: high quality of ophthalmic biodegradable curative nonallergic films of high adhesive capacity; simplified production process.

Description

The invention relates to medicine, namely to experimental and clinical surgery, ophthalmology, transplantology, cosmetology, and can be used to restore the mucous membranes, cornea, conjunctiva.

An original solution to the problem of prolongation and accurate dosing of ophthalmic drugs was the creation of the Moscow Research Institute of Eye Diseases named after Helmholtz and the All-Union Research Institute of Medical Technology of soluble ophthalmic drug films (HFP) on a polymer basis [1, 2].

V.A. Nuritdinov [3] investigated the properties of HAC based on polyacrylamide and the penetration of the injected substance into the anterior chamber of the eye. Studies have shown that polyacrylamide films in the conjunctival sac are the depot of the administered substance, after complete dissolution of the polymer mass, intense fluorescein saturation of the conjunctiva, sclera, cornea in the area where the film was located was found. Mechanical damage to the epithelium by the film was not seen in any eye. The effectiveness of the studied method can be explained by the slow rate of release of the introduced substance from the polyacrylamide mass and its adhesion to the surface of the eyeball. As a result, the excretion of the drug from the conjunctival cavity into the tear ducts is slowed down, the duration of contact with the surface of the eye increases, and penetration through the cornea increases. In addition, the cornea and sclera in the area of adhesion of the film become a kind of secondary depot, from which the injected substance continues to enter the eyes even of the complete dissolution of the polymer mass.

HLP have several advantages over other dosage forms used in ophthalmology. First of all, it is precise controlled dosing and prolonged drug exposure. As a result of the experimental work carried out by Yu.F. Maychuk, V.P. Yerichev [4, 5], it was established that HLP with pilocarpine have a pronounced prolonged hypotensive effect, are well tolerated by patients, and have significant advantages compared with an aqueous solution of pilocarpine and membrane OKUSEPT system.

On the same biologically soluble biologically soluble biocompatible polymer with eye tissues, eye films with fibrinolysin have been developed [6], which contain fibrinolysin in an amount of 400–450 units in each film.

Polymer-based SODs were oval-shaped plates of 9 × 4.5 × 0.35 mm in size, which were inserted into the lower conjunctival arch after preliminary anesthesia with 0.5% dicaine solution. The film in the conjunctival cavity is moistened with a tear and after 10-15 seconds it becomes elastic. Within 40-60 from the eyes it adapts to the introduction of the film and further discomfort is not felt.

Currently, there is experience in the use of HFR with kanamycin for microtrauma of the cornea in combination with magnetophoresis 40-50 minutes after the film was laid, a good practical result was achieved, the duration of the disease was reduced [8].

T.I. Davidenko et al. (patent No. 2009921, 1994) a basis for ophthalmic drug films of proteolytic enzymes is proposed. The base contains a homopolymer of acrinolic acid amide with a molecular weight of 36000-1000000 and a copolymer of acrylic acid amide with unsaturated compounds with a molecular weight of the copolymer of 20000-500000 and the content of acrylic units 90% and peat.

A.D. Romashchenko (patent No. 2056819, 1996) has been proposed for the treatment of intraocular hemorrhage of HFD three-layer, which contains a base of a bio-soluble polymer, streptodecase and emoxipin [7].

M.T.Aznabaev et al. (Patent No. 2076672, 1997) proposed HFRs containing crushed native cornea in cattle - 3%, rosehip oil - 3.5%, polyacrylamide - 93.5%.

M.T.Aznabaev et al. (patent No. 2160074, 1998), ophthalmic films of the following composition were proposed (wt.%): a mixture of glycosaminoglycans 1.0, polyacrylamide 94.0, pyobacteriophage purified polyvalent liquid 5.0.

M.T.Aznabaev et al. (Patent No. 2173178, 2001) proposed ophthalmic films containing a shredded native cornea of cattle eyes 0.25 g, polyvinyl alcohol 99.25 g, gamma globulin 0.25 g, gentamicin 0.25 g.

Closest to the claimed invention, HFL is three-layer, which contains a base of a bio-soluble polymer, streptodecase and emoxipin, proposed by A.D. Romashchenko for the treatment of intraocular hemorrhage (patent No. 2056819, 1996). The manufacturing method consists in the fact that a solution of emoxipin in a polymer solution is applied to a substrate, dried in a stream of warm air with a temperature of not more than 40 ° C to a residual film moisture of 20-30%, and then a streptodease solution in a polymer solution is similarly applied, dried temperature up to 40 ° C to a residual moisture of the film 5-7%, then the film is packaged and sterilized.

The disadvantages of the proposed A.D. Romashchenko GLP are:

- multi-stage film production;

- the polymer base of SODI, which is a carrier of a medicinal substance, and not an active agent,

- streptodecase, which is part of GLP, has a pronounced allergenic property;

- cannot be used to treat corneal ulcers.

The technical result is to simplify the method of obtaining HFD with a reduction in time costs.

The technical result is achieved by preparing an aqueous solution of sodium alginate and calcium gluconate in a ratio of sodium alginate - 73%, calcium gluconate - 27%. The prepared mixture of components from the tank is poured with a layer of 1 mm into pallets. Separating lattices are inserted into pallets according to a given standard size (10 mm × 7 mm) oval. Simple convection drying of the product for 8 hours. At the end of the process, we obtain films with a thickness of 0.1 mm, 10 × 7 mm. We pack and sterilize.

Thus, the proposed method for producing HFP is technically simple (single-stage), it takes about 8 hours. This GLP can be used to treat corneal ulcers of various origins, hypoallergenic (clinically proven).

Clinical example. Patient K., 77 years old, source of illness No. 7246, in hospital treatment at the Regional Clinical Ophthalmological Hospital since 24.10. on November 6, 2001, with a diagnosis of left eye - purulent corneal ulcer. Against the background of traditional therapy (talsef, gentamicin, normax, calcium gluconate, ascorbic acid), a defect of 3 × 2 mm remained in the deep layers of the cornea for 7 days. HLP was applied 1 time per day for 5 days - HLP was applied to the cornea with sterile forceps, normal drops of Normax were installed, HLP turned into a gel state after 15 seconds, after closing the eyelids, a monocular dressing was applied for 6 hours. On the second day of HFL application, the defect in the cornea decreased in area and depth by 1 mm, on the third day, the defect remained, but perifocal corneal infiltration decreased significantly, on the fourth day, the defect was further reduced by 1 mm, a corneal scar was formed with residual infiltration, on the fifth day of the use of SODI, the defect was completely epithelized, and a corneal scar was formed. The patient was discharged home.

The use of HFP developed by us will improve the treatment of ulcerative lesions of the cornea of various origins (purulent corneal ulcer, deep viral or neutrophic keratitis with descemetocele) without a side effect. The pH of such films is close to neutral. Such films are completely biodegradable and non-allergenic. Alginate films have high adhesion, when they absorb wound contents they turn into a gel, which practically removes the effect of foreign presence in the eye. The low cost of components, ease of preparation will allow ophthalmologists to provide a highly effective method of treating severe eye pathology, which often leads to the removal of the eyeball, without unnecessary costs. The methodology for the use of the proposed HFP does not require high qualifications or special training for ophthalmologists. In the Voronezh Regional Clinical Hospital, 40 patients were treated with ulcerative lesions of the cornea of various origins using ocular drug films based on sodium alginate prepared by the method proposed by the authors.

Information sources

1. Maychuk Yu.F. - In the book: Anniversary scientific-practical conference. ophthalmologists of Moscow. Materials M., 1967, p. 403-405.

2. Maychuk Yu.F., Davydov A.B., Khromov G.L. - In the book: All-Union Conf. Inventors and innovators in the field of ophthalmology. 4th. Abstracts of reports. M., 1976, p. 74-75.

3. Nuritdinov V.A. Polyacrimide as the basis of ophthalmic medicinal films // Bulletin of Ophthalmology. - 1981. - No. 2. - p. 59-60.

4. Maychuk Yu.F., Yerichev V.P. Pharmaceutical and clinical evaluation of soluble eye films with pilocarpine // Bulletin of Ophthalmology. - 1981. - No. 2. - p. 48-49.

5. Maychuk Yu.F., Yerichev VP, Salminen L. Influence of various medicinal bases on the miotic effect of pilocarpine // Bulletin of Ophthalmology. - 1982. - No. 4. - p.16-17.

6. Malanova N.L., Murzin A.A. et al. Medicinal films with fibrinolysin in ophthalmology // Bulletin of Ophthalmology. - 1979. - No. 3. - p. 58-59.

7. Romashchenko A.D. Patent RU 2056819 C1. Ophthalmic drug film and method for its manufacture. 03/27/1996. Bull. No. 9.

8. Shif L.V., Novikov Ya.S. et al. Magnetophoresis using ophthalmic medicinal films for microtrauma of the cornea // Ophthalmic Journal. - 1989. 4th. Abstracts of reports. M., 1976, p. 74-75.

Claims (1)

A method of producing eye films for the treatment of ulcerative lesions of the cornea of various origins, characterized in that an aqueous solution of sodium alginate and calcium gluconate, taken in a ratio of 73 and 27%, respectively, is poured in the form of a mixture into a tray with a 1 mm layer with oval separating lattices, then carry out convection drying for 8 hours