Currently, in the Russian Federation there is a tendency towards the abuse of some new anticholinergic drugs. They are taken instead of traditional drugs and psychoactive substances as they are less expensive and more accessible. Taking them is not considered a criminal offense. In recent years, cases of non-medical use of the following anticholinergic drugs have been reported in the country: trigana D (active ingredient dicycloverine), cyclomed (active ingredient cyclopentolate), tropicamide. These drugs are used for non-medical purposes by various categories of the population. Cyclomed, as a rule, is used by young people from 16 to 20 years old, who select “suitable” and affordable medications for themselves in order to put themselves in a state of intoxication [1].
For non-medical purposes, Cyclomed is used intranasally in excess of the therapeutic dose several times in order to develop visual and auditory hallucinations and changes in the emotional state. The effect of such use is disorientation in space, distortion of speech and vision, memory loss, etc., characteristic of an overdose of the drug. The literature contains clinical data on the abuse of cyclopentolate (Cyclomed) by patients who are being treated for alcohol and heroin addiction [2].
There are no methods for chemical-toxicological analysis of material evidence and biological fluids in case of cyclopentolate poisoning and do not allow making a conclusion about the use of this drug for non-medical purposes, including when taken together with narcotic and psychotropic drugs.
The purpose of the study is to develop methods for the chemical-toxicological analysis of cyclopentolate in material evidence and biological fluids during forensic chemical and chemical-toxicological examination.
Objects of research
Cyclomed (1% solution), active agent - cyclopentolate hydrochloride; The chemical name is 2-dimethylaminoethyl-2-(1-hydroxycyclopentyl)-2-phenylacetate hydrochloride. The drug is well absorbed through the conjunctiva, the detectable concentration in the central nervous system is achieved after 0.5-1 hour. Cyclopentolate binds to plasma proteins by 40-60% after 0.5-2 hours [3].
Naphthyzin (0.1% solution) according to its pharmacological action is classified as an adrenergic agonist, affecting mainly α-adrenergic receptors; the active agent is naphazoline nitrate; chemical name is 2-(α-naphthylmethyl)-imidazoline nitrate. Data on the pharmacokinetics and pharmacodynamics of the drug were not found in the available literature.
Tropiconamide (1% solution), according to its pharmacological action, belongs to M-anticholinergic blockers, is used in the treatment of eye diseases.
Substances
codeine, morphine are isolated from toxidiscs of the TOXI-LAB system.
Biological fluids
(blood, urine) experimental animals (rats).
During the study, cyclopentolate isolated from a dosage form (drops) of a 1% solution of cyclomed was used as a working standard sample (RSS), the authenticity and purity of which were confirmed by chemical and physicochemical methods of analysis [4].
Material and methods
When developing a method for the chemical and toxicological analysis of cyclomed in physical evidence and biological fluids, the following equipment was used: ultraviolet (UV) spectrophotometer SF 2000; Agilent 1200 liquid chromatograph with diode array detector (DMF); gas chromatograph Agilent HP 6850 with mass selective detector HP 5973N (USA); Sorbfil PTSKH-P-A-UF plates with a polymer backing.
To carry out color and sediment reactions and physicochemical studies, we used Dragendorff, Markey, Mundellin, Bushard-Wagner reagents, concentrated sulfuric and nitric acids, 0.1 M hydrochloric acid solution, aqueous ammonia, anhydrous sodium sulfate; reagent grade and analytical grade solvents: chloroform, ethanol, acetone, 2-propanol, ethyl acetate, hexane, acetonitrile.
Results and discussion
Isolation of cyclopentolate from aqueous solutions was carried out with various solvents (chloroform, ethyl acetate, hexane and a mixture of chloroform-2-propanol in a ratio of 9:1) at pH values from 2.0 to 12.0. The percentage of recovery of cyclopentolate from aqueous solutions was determined by UV spectroscopy in a 0.1 M solution of hydrochloric acid at a wavelength of 257 nm according to a pre-constructed calibration graph.
The maximum extraction of cyclopentolate from an aqueous solution was observed at a pH of 10.0 using a mixture of chloroform-2-propanol in a ratio of 9:1 (75%), chloroform (65%), ethyl acetate (53%) and hexane (46%). The use of the salting out agent sodium chloride during extraction did not increase the percentage of recovery of the analyte.
Technique for isolating the analyte from physical evidence
(cyclomed solution): purified water was added to part of the cyclomed solution at a pH of 10.0, then transferred to a separatory funnel and extraction was carried out 3 times with 5 ml for 5 minutes with a mixture of chloroform-2-propanol (9:1). The organic layer was separated, passed through anhydrous sodium sulfate, the extracts were combined and evaporated in a stream of warm air to a dry residue.
To identify the cyclopentolate base isolated from cyclomed, the following methods were tested: color and sediment reactions [5], thin layer chromatography (TLC), UV spectroscopy, high performance liquid chromatography (HPLC) and gas chromatography with a mass selective detector (GC/MS) [6, 7].
If the circumstances of the study (at the scene) or the laboratory equipment do not allow the use of complex, highly sensitive equipment, color and sediment reactions are carried out as one of the preliminary stages of the study (Table 1). A solution with a known concentration (0.1 mg/ml) was prepared in chloroform or ethanol, then it was diluted with the appropriate solvent in volumetric flasks and an aliquot with a certain amount in the cyclopentalate solution was taken with a microsyringe; the solvent was evaporated in a stream of warm air and the detection limit of the substance under study was determined.
Table 1. The effect of the interaction reaction of cyclopentolate with some reagents used in chemical toxicological analysis
TLC at the preliminary stage serves as the main source of information in forensic chemical and chemical toxicological analysis [7]. Chromatographic study of cyclopentolate was carried out by one-dimensional ascending chromatography in various solvent systems on Sorbfil PTSH-P-A-UV plates with a polymer support (Table 2).
Table 2. Rf values of cyclopentolate during chromatography in various solvent systems
It has been established that the optimal solvent system for the determination of cyclopentolate by TLC together with tropicamide, naphazoline, morphine and codeine is the system ethyl acetate - ethanol - aqueous ammonia (17:3:1) [8].
UV spectroscopy was used to identify the cyclopentolate isolated from solution. In UV spectra obtained in a 0.1 M solution of hydrochloric acid, the maximum absorption of cyclopentolate is observed at wavelengths of 252, 258 and 264 nm. The recorded spectra turned out to be identical to the spectra given in the literature [4, 6].
To study cyclomed containing cyclopentolate, together with tropicamide and naphazaline, GC/MS and equipment (USA) were used: gas chromatograph Agilent HP 6850 (with mass selective detector HP 5973N), capillary column HP-5 MS (5% phenylmethylsiloxane) internal diameter 0.25 mm and 30 m long, helium carrier gas, flow rate 0.8 ml/min, temperature from 80 (0.5 min) to 100 °C, final temperature 290 °C, sample volume 1 μl.
For chromatography, we used the dry residue of the chloroform extract, which was dissolved in 100 μl of methanol. The retention time for cyclopentolate was recorded to be 7.95 minutes. In the mass spectrum, characteristic peaks of ions with m/z 58, 71, 72, 207, 42, 91, 59 and 118 were observed; the resulting spectrum coincided with the library data. For naphazoline and tropicamide, the retention time of this method under these conditions was 12.45 and 16.3 minutes, respectively (Fig. 1).
Rice. 1. Determination of cyclopentolate in the presence of naphazoline and tropicamide using the GC/MS method.
To identify and quantify cyclopentolate, HPLC was used, which makes it possible to isolate the substance from complex mixtures of organic compounds and simultaneously analyze it both qualitatively and quantitatively.
The analysis was carried out using equipment: Agilent 1200 liquid chromatograph with DMD; pre-column Zorbax Eclipse XDB - C 185 µm 4.6×12.5 mm, column Zorbax Eclipse XDB - C 185 µm 4.6×150 mm; mobile phase feed rate 1 ml/min; chromatogram recording time 8 min; mobile phase: acetonitrile, phosphate buffer pH 3.0 (60:40); column thermostat temperature 40 °C; volume of injected sample 2 µl; gradient analysis mode; detection wavelength 210 nm. The retention time was recorded for cyclopentolate - 6.17 minutes, naphazoline - 5.21 minutes, tropicamide - 4.25 minutes (Fig. 2).
Rice. 2. Determination of cyclopentolate in its co-presence with naphazoline and tropicamide by HPLC.
Thus, to establish the presence of cyclopentolate in research objects delivered for forensic chemical examination or chemical-toxicological research from the scene as material evidence, TLC, HPLC, GC/MS and UV spectroscopy, as well as color and sediment methods should be used reactions.
Determination of cyclopentolate in biological objects
To determine the percentage of cyclopentolate extraction from biological fluids, model complexes were prepared. We used urine and blood samples from healthy volunteers who had not taken medications for 1 month before sampling. Model mixtures of urine and blood were prepared by adding a working standard solution with a concentration of 10 mg/ml to biofluids to obtain concentrations of 0.5, 1.0, 2.0 mg/ml. The prepared model mixtures were incubated at a temperature of 37 °C for 2 hours. The percentage of cyclopentolate extraction from biological fluids was determined by UV spectrophotometry (Table 3).
Table 3. Percentage of cyclopentolate recovery from model complexes
Blood in an amount of 4-5 ml was diluted with purified water, sodium tungstate solution 10% was added in a volume equal to the amount of purified water, and sulfuric acid solution 10% was added until the pH of the medium was 2.0. The resulting solution was transferred to a centrifuge tube and centrifuged for 5 minutes. The centrifugate obtained after sedimentation of proteins and blood cells was transferred to a separatory funnel, adjusted to pH 10.0 with aqueous ammonia and extracted with a mixture of chloroform-2-propanol (9:1) in portions of 5 ml 3 times. The extracts were combined and passed through a layer of anhydrous sodium sulfate into porcelain cups and evaporated to dryness.
Urine was examined using liquid-liquid extraction at pH 10.0 with a mixture of chloroform-2-propanol (9:1) in three 5-ml portions. The extracts were combined, passed through a layer of anhydrous sodium sulfate into porcelain cups and evaporated to a dry residue.
The developed methods for the chemical and toxicological analysis of cyclopentolate base in biological fluids were tested on experimental animals, since they to a certain extent reproduce the processes that occur with xenobiotics when they are introduced into a living organism.
A study was conducted on 15 outbred white male rats weighing 180-220 g. A solution of Cyclomed was administered intraperitoneally once in an amount of 1 mg of the active substance, followed by the introduction of a water load. The results were compared with data from a control group of 5 animals that received intraperitoneal injections of water for injection. Blood was collected from the gums after 1 and 2 hours, urine was collected within 24 hours. 3 ml of blood and 4-5 ml of urine from each animal were taken for analysis.
Isolation of cyclopentolate base from biological fluids of animals was carried out according to a method we developed using solid-phase extraction (SPE), based on the use of cartridges with different sorption properties, which makes it possible to selectively adsorb substances of different chemical natures on the surface of the cartridge sorbent. The main advantages of the method compared to traditional ones are the possibility of simultaneous isolation and concentration of the substance under study, as well as a significant increase in the speed and efficiency of extraction. Extraction of the test substance was carried out using Oasis HLB cartridges. These cartridges have hydrophilic-lipophilic duality and are capable of adsorbing substances of different chemical natures. The cartridges were washed with 1 ml of methanol and 1 ml of purified water, then loaded with 1 ml of biological fluid (urine or blood plasma). To extract drugs, the cartridges were washed with 1 ml of 5% methanol solution and eluted with 1 ml of chloroform-2-propanol (9:1). The eluate was evaporated to dryness and studied by physicochemical methods. Part of the dry residue was dissolved in 1 ml of grade 0 acetonitrile, and cyclopentalate was quantitatively determined by HPLC. It was possible to increase the extraction of cyclopentalate base by SPE by 2 times compared to liquid-liquid extraction (Table 4). Using the SPE method, it was not possible to select conditions for the extraction of the analyte from urine.
Table 4. Quantitative determination of cyclopentolate in biological fluids
Analysis of extracts from biological fluids after purification was carried out by TLC, UV, HPLC and GC/MS. Cyclopentolate was detected in blood samples after 1 and 2 hours, but the drug was not detected after 3 hours. When studying the extraction from rat urine collected over 24 hours, cyclopentolate and its metabolites were detected by GC/MS (Fig. 3, 4).
Rice. 3. Chromatogram of extraction from blood after 1 hour, obtained by gas chromatography.
Rice. 4. Chromatogram of extraction from urine collected within 24 hours, obtained by gas chromatography.
When studying by TLC, spots were observed that, in terms of Rf value, color and fluorescence, corresponded to the cyclopentolate base isolated from the cyclomed solution. HPLC (blood 6.22; urine 6.25) and GC/MS (blood 7.80; urine 7.84) methods showed that the retention time and mass spectrum of the substance isolated from biofluids coincided with those obtained from the analysis cyclopentolate isolated from a solution of cyclomed.
For the quantitative determination of cyclopentolate in biological fluids, we offer HPLC (calibration graph) and mass spectrometry (internal standard method), for which we have developed specific methods. The discrepancy between the results of quantitative determination obtained by different methods does not exceed 5% (see Table 4).
Some validation characteristics have been determined for the HPLC method. The linearity parameter was determined by measuring solutions of the test substances at 5 concentration levels. The correlation coefficient value was within 0.99< R
<1.0. The precision of the method was determined by the indicators “convergence” and “intralaboratory reproducibility”. The relative standard deviation when assessing these indicators did not exceed 2.3% (with RSD <3%, the variability of the variation series is considered insignificant). Thus, the data obtained are consistent and the methodology is reproducible.
Cyclomed 1% 5ml eye drops
Cyclomed 1% 5ml eye drops
Trade name Cyclomed International nonproprietary name Cyclopentolate Dosage form Eye drops 1% Composition 1 ml of the drug contains the active substance - cyclopentolate hydrochloride 10 mg, excipients: benzalkonium chloride, disodium edetate, sodium chloride, sodium hydroxide, water for injection. Description Transparent, colorless solution Pharmacotherapeutic group Drugs for the treatment of eye diseases. Anticholinergics. ATC code S01FA04 Pharmacological properties M-cholinergic receptor blocker for topical use in ophthalmology. It has a mydriatic effect, impedes the outflow of intraocular fluid, increases intraocular pressure, and causes paralysis of accommodation. With systemic action, it reduces the secretion of the salivary, gastric, bronchial, sweat glands, pancreas, reduces the tone of the muscles of the gastrointestinal tract, bile ducts and gallbladder, causes tachycardia, improves AV conduction. In high doses, it stimulates the cerebral cortex. It acts quickly, but less lasting than atropine. The maximum effect develops 75 minutes after instillation. Complete restoration of accommodation usually occurs within 6-24 hours, in individual cases - after several days. Indications for use - diagnostics of fundus examination and determination of refraction - in ophthalmic surgery in preoperative preparation for pupil dilation during cataract extraction - in complex therapy of inflammatory diseases of the anterior part of the eye (episcleritis, scleritis, keratitis, iridocyclitis, uveitis) Method of administration and dosage Apply topically, instilling 1 - 2 drops into the conjunctival sac. Examination of the fundus - instill 1-3 times, 1 drop every 10 minutes. Refraction testing in children and adolescents - 2-3 times, 1-2 drops every 15-20 minutes (in children under 2 years of age, it is not recommended to use the drug in concentrations above 0.5%). Inflammatory eye diseases - 1 drop 3 times a day; in severe cases, Cyclomed can be instilled every 3 to 4 hours. To reduce systemic absorption, it is recommended to press the nasolacrimal punctum during the procedure and for 2-3 minutes after it (especially in children). Side effects - redness of the conjunctiva, burning, discomfort after instillation, blepharoconjunctivitis, punctate keratitis - increased intraocular pressure in patients with primary glaucoma, photophobia, decreased visual acuity, eye irritation, hyperemia In rare cases, manifestations of systemic effects (usually in children) - weakness, nausea, dizziness, tachycardia, drowsiness, intestinal atony, bladder atony, anxiety, hallucinations, increased activity, disturbance of temporal and spatial orientation Other: skin rashes, bloating in children, thirst or dry mouth, tachycardia, hyperpyrexia, vasodilation, retention urine, weakening of gastrointestinal motility, decreased secretion of glands (sweat, salivary, mucous membranes of the ENT organs and bronchi) Contraindications - hypersensitivity to the components of the drug - suspicion of glaucoma, glaucoma - post-traumatic paresis of the musculus sphincter pupillae of the iris - pregnancy and lactation - childhood up to 8 years Special instructions When instilling the solution into the conjunctival sac, in order to avoid the solution getting into the nasopharynx, it is advisable to press the lower lacrimal opening. Cyclomed is less effective in individuals with dark-pigmented irises. In these individuals, when using the drug, residual accommodation can reach 2–4 diopters. In children with semi-persistent or persistent spasm of accommodation, it is better to use a course of atropine sulfate instillations for cycloplegia. Persons sensitive to atropine sulfate do not have a cross-allergy to Cyclomed, which allows its use in this category of patients. If photophobia occurs, you must wear sunglasses to protect your eyes from UV light. If photophobia and/or blurred vision does not resolve within 36 hours after instillation, you should consult a doctor. In patients over 40 years of age, the use of Cyclomed requires monitoring of intraocular pressure and gonioscopy, if necessary. Use in pediatrics Use with caution in children over 8 years of age, in children with Down syndrome, with spastic paralysis or cerebral disorders, in light blue-eyed children (characterized by increased sensitivity to the action of cyclopentolate). With caution Old age; intestinal obstruction; prostatic hyperplasia. Peculiarities of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms. Patients who temporarily lose clarity of vision after application of the drug are not recommended to drive vehicles or work with complex machinery, machines or other complex equipment. Drug interactions The effect of Cyclomed can be enhanced by sympathomimetics (mesaton), weakened by M-cholinomimetics (pilocarpine), cholinesterase inhibitors, carbacholine. Overdose When strictly following the doctor's prescriptions, no cases of overdose were observed. Symptoms: when the recommended doses are increased or when the drug is accidentally taken orally, the following are possible: dry skin and mucous membranes, tachycardia, agitation, incoherent speech, fatigue, impaired recognition of nearby objects, disorientation in time and space, changes in emotional state; at very high doses - respiratory paralysis and coma. Treatment: intravenous administration of a specific antidote - physostigmine, for children at a dose of 0.5 mg, if necessary (if there is no effect after 5 minutes), the dose is repeated (the maximum dose should not exceed 2 mg); For adults, the antidote is administered at a dose of 2 mg; if there is no effect after 20 minutes, the administration is repeated at a dose of 1-2 mg. Release form and packaging 1% solution of 5 ml in a plastic dropper bottle with a screw cap. Each dropper bottle, along with a cap and instructions for medical use in the state and Russian languages, is placed in a cardboard box. Storage conditions Store at temperatures up to 25ºС, protected from light. Do not freeze. Keep out of the reach of children! Shelf life: 2 years After first opening, the contents of the bottle can be used for no more than 1 month. Do not use after the expiration date stated on the packaging. Conditions for dispensing from pharmacies By prescription
conclusions
1. Isolation of the analyzed substance from physical evidence should be carried out using liquid-liquid extraction with a mixture of chloroform-2-propanol (9:1) at a pH of 10.0, and from biological fluids under the same conditions after preliminary precipitation of blood proteins and without preliminary acid hydrolysis for urine.
2. It has been established that the methods of TLC, GC/MS, HPLC, and UV spectroscopy make it possible to identify the component of the drug Cyclomed in physical evidence and biological fluids.
3. Conditions have been developed for the quantitative determination of cyclopentolate isolated from biological fluids using high-performance liquid chromatography and gas chromatography-mass spectrometry.
There is no conflict of interest.
Cyclomed eye drops 1% 5.0 ml (cyclopentolate)
Full description
[RU]
Tradename
Cyclomed
International nonproprietary name
Cyclopentolate
Dosage form
Eye drops 1%
Compound
1 ml of the drug contains
active substance - cyclopentolate hydrochloride 10 mg,
excipients: benzalkonium chloride, disodium edetate,
sodium chloride, sodium hydroxide, water for injection.
Description
Transparent, colorless solution
Pharmacotherapeutic group
Drugs for the treatment of eye diseases. Mydriatics. Anticholinergics.
Cyclopentolate.
ATX code S01FA04
Pharmacological properties
Pharmacokinetics
M-cholinergic receptor blocker for local use in ophthalmology. It has a mydriatic effect, impedes the outflow of intraocular fluid, increases intraocular pressure, and causes paralysis of accommodation. With systemic action, it reduces the secretion of the salivary, gastric, bronchial, sweat glands, pancreas, reduces the tone of the muscles of the gastrointestinal tract, bile ducts and gallbladder, causes tachycardia, improves AV conduction. In high doses, it stimulates the cerebral cortex.
It acts quickly, but less lasting than atropine. The maximum effect develops 75 minutes after instillation. Complete restoration of accommodation usually occurs within 6-24 hours, in individual cases - after several days.
Indications for use
- diagnostic examination of the fundus and determination of refraction
- in ophthalmic surgery in preoperative preparation for pupil dilation during cataract extraction
- in complex therapy of inflammatory diseases of the anterior part of the eye (episcleritis, scleritis, keratitis, iridocyclitis, uveitis)
Directions for use and doses
Apply topically, instilling 1 - 2 drops into the conjunctival sac.
Examination of the fundus - instill 1-3 times, 1 drop every 10 minutes.
Refraction testing in children and adolescents - 2-3 times, 1-2 drops every 15-20 minutes.
Inflammatory eye diseases - 1 drop 3 times a day; in severe cases, instillation of Cyclomed 1 drop every 3 - 4 hours is allowed.
To reduce systemic absorption, it is recommended to press the nasolacrimal punctum during the procedure and for 2-3 minutes after it (especially in children).
Side effects
- redness of the conjunctiva, burning, discomfort after instillation, blepharoconjunctivitis, punctate keratitis
- increased intraocular pressure in patients with primary glaucoma, photophobia, decreased visual acuity, eye irritation, hyperemia
In rare cases of systemic effects (usually in children)
- weakness, nausea, dizziness, tachycardia, drowsiness, intestinal atony, bladder atony, anxiety, hallucinations, increased activity, disturbance of temporal and spatial orientation
Other: skin rashes, bloating in children, thirst or dry mouth, tachycardia, hyperpyrexia, vasodilation, urinary retention, weakened gastrointestinal motility, decreased secretion of glands (sweat, salivary, mucous membranes of the ENT organs and bronchi)
Contraindications
- hypersensitivity to the components of the drug
- suspicion of glaucoma, glaucoma
- post-traumatic paresis of the musculus sphincter pupillae of the iris
- pregnancy and lactation period
- children up to 8 years old
special instructions
When instilling the solution into the conjunctival sac, in order to avoid the solution entering the nasopharynx, it is advisable to press the lower lacrimal punctum. Cyclomed is less effective in individuals with dark-pigmented irises. In these individuals, when using the drug, residual accommodation can reach 2–4 diopters.
In children with semi-persistent or persistent spasm of accommodation, it is better to use a course of atropine sulfate instillations for cycloplegia.
Persons sensitive to atropine sulfate do not have a cross-allergy to Cyclomed, which allows its use in this category of patients.
If photophobia occurs, you must wear sunglasses to protect your eyes from UV light. If photophobia and/or blurred vision does not resolve within 36 hours after instillation, you should consult a doctor.
In patients over 40 years of age, the use of Cyclomed requires monitoring of intraocular pressure and gonioscopy, if necessary.
Use in pediatrics
Use with caution in children over 8 years of age, in children with Down syndrome, with spastic paralysis or cerebral disorders, in light blue-eyed children (characterized by increased sensitivity to the action of cyclopentolate).
Carefully
Elderly age; intestinal obstruction; prostatic hyperplasia.
Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms
Patients are not recommended to drive vehicles or work with complex machinery, machines or other complex equipment.
Drug interactions
The effect of Cyclomed can be enhanced by sympathomimetics (mesaton), weakened by M-cholinomimetics (pilocarpine), cholinesterase inhibitors, carbacholine.
Overdose
If the doctor's prescriptions were strictly followed, no cases of overdose were observed. Symptoms: when the recommended doses are increased or when the drug is accidentally taken orally, the following are possible: dry skin and mucous membranes, tachycardia, agitation, incoherent speech, fatigue, impaired recognition of nearby objects, disorientation in time and space , change in emotional state; at very high doses - respiratory paralysis and coma.
Treatment: intravenous administration of a specific antidote - physostigmine, for children at a dose of 0.5 mg, if necessary (if there is no effect after 5 minutes), the dose is repeated (the maximum dose should not exceed 2 mg); For adults, the antidote is administered at a dose of 2 mg; if there is no effect after 20 minutes, the administration is repeated at a dose of 1-2 mg.
Release form and packaging
Eye drops 1%.
5 ml of the drug in plastic dropper bottles.
1 dropper bottle together with a screw cap, inside of which there is a device for opening the bottle and with instructions for medical use in the state and Russian languages, is placed in a cardboard box.
Storage conditions
Store in a place protected from light at a temperature not exceeding 25°C.
Do not freeze.
Keep out of the reach of children!
Shelf life
2 years
The period of use after opening the bottle is 1 month.
Do not use after the expiration date indicated on the package!
Conditions for dispensing from pharmacies
On prescription
Manufacturer
SENTISS PHARMA Pvt. Ltd.
212/D-1, Green Park, New Delhi, India
At Factory: Khera Nikhla Village, Nalagarh Tehsil, Solan District, Himachal Pradesh 174 101, India
Name and country of the marketing authorization holder
SENTISS PHARMA Pvt. Ltd., India
Address of the organization that accepts claims from consumers regarding product quality on the territory of the Republic of Kazakhstan:
Republic of Kazakhstan, 050000, Almaty, st. Bogenbai Batyr 132, office 309
Tel/fax
Email: [email protected]
