RU2331408C1 - Ophthalmic ointment - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of medicine, particularly ophthalmology, and can be applied to treatment for dystrophy or traumatic erosion of cornea, various keratitis, and chemical burns of conjunctiva and cornea. The ophthalmic ointment includes aecol as active substance, and ingredients in certain ratio: methylcellulose, polyvinyl pyrrolidone, nipagin, and nipazole, as ointment base.

EFFECT: increase in therapeutic efficacy of eye ointment, and reduction of treatment period for eye traumatic injury.

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Description

The invention relates to medicine, in particular to ophthalmology, and can be used in the treatment of dystrophy, traumatic erosion of the cornea, various keratitis, chemical burns of the conjunctiva and cornea.

Known ophthalmic ointment 3% xeroform on a lanolin-vaseline basis, the drawback of which is the appearance of allergic reactions due to the presence of lanolin and petroleum jelly, as well as insufficient wound healing activity of drugs (Tentsova A.I., Alyushin M.T. Polymers in pharmacy. M., Medicine, 1980, p. 10).

The closest in technical essence to the claimed technical solution is an eye ointment containing rosehip oil as a medicinal substance, and methyl cellulose, glycerin, T-2 emulsifier and water as a base in the following ratio of components, wt.%:

Rosehip oil 5-10 Cellulose 1-3 Glycerol 7-15 Emulsifier T-2 0.5-2 Water Rest

This ointment is used as a wound healing agent for trophic and burn defects of the cornea and conjunctiva, sluggishly healing wounds of the cornea, traumatic keratitis, skin and mucosal defects. In the process of treatment, the inflammatory reaction, lacrimation and photophobia are reduced, epithelization of damaged surfaces occurs (RF patent No. 2000750, IPC АКК 35/78, 1993).

However, for all its positive properties, an eye ointment with rosehip oil has insufficient regeneration, which is explained by a lower concentration of the active substance B-carotene.

The objective of the invention is the expansion of the arsenal of healing agents in the treatment of eyes.

The technical result is to increase the therapeutic effect and reduce treatment time.

The technical result is achieved in that the eye ointment containing the active substance, methyl cellulose as a base and purified water, contains Aecol as the active substance, and additionally contains polyvinylpyrrolidone, nipagin, nipazole in the following ratio, wt.%:

Aekol 2.5-5.0 Polyvinylpyrrolidone 1.0-2.5 Cellulose 2.5-4.0 Nipagin 0.08 Nipazole 0.02 Purified water 93.9-88.4

The ointment is prepared as follows: methyl cellulose is poured with hot purified water. After swelling and dissolution of methylcellulose, polyvinylpyrrolidone, readily soluble in methylcellulose solution, is added. The base is sterilized. A sterile base, nipagin / nipazole, aecol is placed in a sterile glass of the RT-2 device and everything is thoroughly homogenized at 3000 rpm for 2 minutes until a homogeneous mass is formed.

Method of application: ointment is laid over the eyelid 3-6 times a day with a glass rod.

Analysis of the known bases showed that the base in the form of a solution of methyl cellulose is known in medicine, but the introduction of additional polyvinylpyrrolidone can reduce interfacial tension at the phase boundary of the base, increases its stability and prevents the ointment from leaching with tear fluid.

Polyvinylpyrrolidone easily forms complexes with medicinal substances (Tikhonov A.I. Ophthalmic drugs with a phenolic preparation of propolis. In the book. Theoretical foundations of the preparation of drugs and their biopharmaceutical evaluation. M., 1983, p. 43, Sergeev A.V., Vakulova L. .N. / Questions of medical chemistry /, 1992, S. 8-12), including with vitamins, increasing their solubility and absorption. Polyvinylpyrrolidone is successfully used to modify the properties of drugs. The introduction of polyvinylpyrrolidone in the dosage form allows to increase the concentration of the active substance in solution and to obtain more stable preparations (Khristenko A.A., Salo D.T., Pertsev N.M. On the study of ocular drug films. Pharmaceutical journal /. 1979, No. 3 , Pp. 51-54.)

The introduction of even a small amount of Aecol into the ointment significantly enhances the regenerative effect, since it is a more active complex preparation compared to rosehip oil, in addition, the process of obtaining Aecol is less time-consuming (they produce carotenoids in a biotechnological way). The biological value of microbiological carotene, according to the literature, significantly exceeds the activity of plant carotenoids (Bukin V.N. Biochemistry of vitamins. Selected works. M., Medicine, 1982. Yakovlev TV. Therapeutic and preventive vitaminology. - M., 1981, p. 150) and the final yield requires significantly less time and starting materials.

Components of Ophthalmic Ointment

Aekol (VFS 42-168287)

Composition: solution of retinol acetate in oil 8.6%

(GFH st. 579) - 1.04 (282608 ME of vitamin A)

L-tocopherol acetate - 0.18

(GFH st. 695)

2 methyl-1,4-naphthoquinone - 0.21

(TU 64-5-9-84) Vitamin K ₃

Microbiological carotene

(Provitamin A) in oil up to 100 ml

(TU 64-6-149-80)

In terms of B-carotene, there must be at least 180 mg%

The multivitamin preparation Aekol has a healing effect, stimulates reparative processes.

Water-soluble methyl cellulose (TU 6-01-717-72)

It is a methyl ester of cellulose containing 26-33% methoxy groups. The fibrous material is white with a yellowish or grayish tint. At room temperature, it forms aqueous, transparent, viscous solutions. Aqueous solutions of methylcellulose have a large binding, emulsifying, dispersing, wetting and adhesive ability.

Polyvinylpyrrolidone (FS 42-1194-78) (PVPr)

It is a polymer of N-vinylpyrrolidone. It is a colorless, transparent, hygroscopic, thermoplastic polymer with a molecular weight of 10,000 to 1,000,000 and a density of 1,190 kg / m ³ . PVPr is soluble in water and a number of organic solvents (aliphatic alcohols, chloroform, glycerin, polyethylene glycol, ethylene glycol, etc.) Insoluble in aliphatic and aromatic hydrocarbons, chlorobenzene, etc.) Aqueous polymer solutions have a pH of 5.0. The hydrophilic-lipophilic balance of the polymer is 14.89 - it is a stabilizer.

As preservatives in the manufacture of all ointment compositions, parahydroxybenzoic acid esters - parabens (nipagin, nipazole) were used. They are widely used in the pharmaceutical industry in many countries.

Nipagin is a methyl ester of parahydroxybenzoic acid.

Nipazole is propyl ester of parahydroxybenzoic acid. In view of the difficult solubility, it is recommended to use a combination of propyl and methyl esters (1: 3), in which a stronger preservative effect is achieved (Sandalova L.V. On the stability of ointment bases. In the book. Current problems of drug technology. - M., 1983). An especially effective and reliable mixture of ingredients in this ratio for the preservation of ointments.

Purified water

Colorless, clear, odorless and tasteless liquid. pH 5.0-6.8 meets the requirements of GF XI edition.

For experimental verification of the claimed composition were prepared compositions of the ingredients (table), 3 of which showed optimal results.

Example 1

Eye ointment with components, which are taken in the following ratio, wt.%:

Aekol 2.5

Polyvinylpyrrolidone 1.0

Methyl cellulose 2.5

Nipagin 0.08

Nipazole 0.02

Purified water 93.9 ml

The method of obtaining the ointment is as follows:

2.5 grams of methyl cellulose is poured into 93.9 ml of hot (90 ° C) purified water. After swelling and dissolving the methylcellulose, 1.0 grams of polyvinylpyrrolidone is added, which dissolves well in an aqueous solution of methylcellulose. The base is subjected to fluid steam sterilization at 100 ° C for 30 minutes or in an autoclave at 120 ° C for 8-10 minutes. A sterile base, nipagin / nipazole (0.08 + 0.02) and 2.5 grams of Aecol are placed in a sterile glass of the RT-2 device and everything is thoroughly homogenized at 3000 rpm for 2 minutes until a homogeneous mass is formed.

Example 2

An eye ointment is prepared analogously to example 1, but the components are taken in the following ratio, wt.%:

Aekol 3,5

Polyvinylpyrrolidone 2.0

Cellulose 3.0

Nipagin 0.08

Nipazole 0.02

Purified water 91.4 ml

Example 3

An eye ointment is prepared analogously to example 1, but the components are taken in the following ratio, wt.%:

Aekol 5.0

Polyvinylpyrrolidone 2.5

Cellulose 4.0

Nipagin 0.08

Nipazole 0.02

Purified water 88.4 ml

Experimental studies have shown that an ointment containing components in the interval of examples 1-3 meets all the requirements of the State Pharmacopoeia of the X-XI edition (uniformity, stability, is well applied to the affected areas). With an increase or decrease in the number of components from this interval, the ointment exfoliates and does not meet the requirements of the Global Fund X-XI edition. Ready-made ointment of yellow color with a characteristic pleasant smell, uniform consistency. The ointment is recommended to be stored in a cool, dark place.

The proposed ointment with optimal concentrations of Aecola was tested in an experiment on 12 rabbits with mechanical erosion of the cornea. The right eye was treated with the proposed ointment, and the left eye (control) with 5% methyluracil ointment. The treatment was carried out 4 times a day. Epithelization of the cornea in the right eye was achieved in all cases when applied with the indicated concentrations of Aecol on the second day. Epithelization of the cornea in the left (control eye) occurred on 3-4 days of treatment.

Conducted experimental studies have allowed the use of the proposed ointment in the clinic.

Presenting examples of the clinical use of the proposed ointment.

Example 4

Patient K., 18 years old, with extensive, subtotal erosion of the cornea of the right eye. Visual acuity at admission 0.4; not corrected; the entire cornea was intensively stained with fluorescein. After a 4-time treatment with an ointment with Aecol content of 2.5 wt.%, A high regenerating effect of the proposed ointment was noted. Corneal epithelization began in the first hours after treatment; marked decrease in photophobia, lacrimation; the disappearance of pain. By the end of the second day of treatment, corneal epithelization was complete. Visual acuity was 1.0.

Example 5

A 26-year-old patient M. received a burn by welding both eyes of the 1st degree. On admission, visual acuity after dikainization was 0.8 / 0.8. The cornea of both eyes is stained with fluorescein, the epithelium is desquamated in the form of white filaments. A 4-time treatment with ointment with Aecol content of 3.5 wt.% Was prescribed. By the end of the first day, a significant improvement was noted. The symptoms of irritation disappeared, epithelization began. After 48 hours, recovery came, visual acuity - 1.0 in both eyes. The cornea does not stain.

Example 6

Patient Z. 30 years old was admitted with a chemical burn of the right eye with lime. After emergency assistance, the I-II degree of burns of the conjunctiva and cornea was established; visual acuity - 0.3, is not corrected. The cornea is edematous in the center and in the lower sector there is an epithelial defect of 1/2 the diameter of the cornea. The conjunctiva of the lower arch and lower eyelid is hyperemic, edematous, the epithelium is desquamated. A 6-time treatment with ointment with Aecol content of 5.0 wt.% Was prescribed. Subjectively, improvement was noted after a 2-time treatment with ointment. Pain in the eye, photophobia and lacrimation, swelling of the eyelids decreased. When viewed after a day, the eyeball is still irritated, but epithelialization of the cornea in the lower sector has begun. In the central zone there is deep erosion of a diameter of 3 mm. By the end of the second day, irritation phenomena disappeared, the conjunctiva became pale pink, the cornea was almost completely epithelized. In the central zone, gentle cloudy turbidity remained. Fluorescein stains single point areas of the corneal epithelium.

Complete epithelization and recovery was achieved after 5 days of treatment. Visual acuity was 0.9.

Thus, the proposed ointment with Aecolum is a highly effective regenerative agent that promotes rapid epithelization of a corneal defect, is well tolerated by patients, does not cause allergic reactions, is economical and convenient to use.

Table Eye ointment The composition of the ointment The content of the components in the ointment Aekol 2.0 2,5 3,5 5,0 6.0 Polyvinylpyrrolidone 0.8 one 2.0 2,5 3.0 Cellulose 0.9 2,5 3.0 4.0 5,0 Nipagin 0.08 0.08 0.08 0.08 0.08 Nipazole 0.02 0.02 0.02 0.02 0.02 Purified water 96.2 ml 93.9 ml 91.4 ml 88.4 ml 85.9 ml

Claims (1)

An eye ointment containing the active substance, methyl cellulose as a base and purified water, characterized in that it contains Aecol as an active substance, and additionally contains polyvinylpyrrolidone, nipagin, nipazole in the following ratio, wt.%: Aekol 2.5-5.0 Polyvinylpyrrolidone 1.0-2.5 Cellulose 2.5-4.0 Nipagin 0.08 Nipazole 0.02 Purified water 93.9-88.4 ml