Vand fontæne og Havebassin

Når foråret kommer begynder vandet at blive grønt af alger

Tilsæt Algerex det forebygger alger hele året

Brug Algerex poly mod gronne belægninger i din have

Til Frede Damgaard & de der måtte overveje at anvende produktet Algerex Poly

Af Produktbladet fremgår, at Algerex Poly er klassificeret:
Farlig ved hudkontakt og ved indtagelse, der er ætsningsfare
Stoffet er meget giftigt for organismer, der lever i vand og kan forårsage uønskede langtidsvirkninger i vandmiljøet.
Bør opsuges i porøst materiale og bortskaffes som kemikalieaffald og ikke hældes i kloakken.

Med venlig hilsen fra
Lone

Algerex poly er et koncentrat som ganske vist har de angivne indikationer

men i brugsopløsningen er det en ganske anden sag

F. eks anvendes dette produkt i Øjendråber og i desinfektio på huden

frede damgaard

Frede Damgård.
Vil du venligst henvise til dokumentation om produktets anvendelse i øjendråber.

Preservatives in Topical Ophthalmic Medications: Benefits, Detriments, and New Developments

by David Freeman, MD

Categorization of Preservatives

Ophthalmic preservatives have traditionally been classified into two categories: detergent or oxidizing preservatives. Recently, a new system of oxidizing preservation, ionic-buffered preservatives, has been introduced. Examples of each category and their mechanisms of action are described.

Detergent preservatives

Detergent-type compounds interrupt the lipid constituent of cell membranes, thereby causing bacterial cell death. The contents of the microbial cell are expunged from the cell due to membrane instability. Cetrimonium and benzalkonium chloride (BAK) are examples of detergent-type preservatives. Detergents also have been used in ophthalmic medicine for the longest period of time.3

Oxidizing preservatives

Oxidative preservatives work by penetrating the lipid membrane of the microbe. Once the oxidizing preservative penetrates, it is able to modify the DNA, protein, and lipid components of bacterial cells.4 Examples of oxidizing preservatives include sodium perborate and stabilized oxychloro complex (SOC).

Given their more recent introduction into ophthalmic medicine and reduced toxicity to human ocular surface cells in comparison to detergent preservatives, they are considered second-generation ophthalmic preservatives. Although ocular surface cells may be injured by oxidative preservatives, the low concentrations contained in ophthalmic preparations deem these effects insignificant.3 Medications preserved with SOC induce less corneal toxicity than those preserved with BAK.5

Ionic-buffered oxidizing preservatives

Ionic-buffering systems are the latest class of ophthalmic preservatives. Their mechanism of action is similar to the oxidizing preservatives listed above. SofZia (Alcon), the most recent preservative of this kind, is a combination of boric acid, zinc, sorbitol, and propylene glycol. When exposed to cations, such as those that are normally encountered in the tear film of the eye, the substance is considered inactive. This system has antibacterial and antifungal qualities.6 Because of its mechanism of action, it is thought to induce less cytotoxicity to the ocular surface compared to more traditional preservatives.

Practical Review of Ophthalmic Preservatives (Table)

Table. Summary of Preservatives Used in Ophthalmic Medicines

Benzalkonium chloride (BAK)

Timoptic (Timolol, Merck)

Azopt (Brinzolamide, Alcon)

Lumigan (Bimatoprost, Allergan)

Xalatan (Latanoprost, Pfizer)

Detergent

Excellent antimicrobial efficacy; disruption of corneal cell-cell junctions allow medicinal entry to anterior chamber; well established familiarity in industry

Breakdown of corneal epithelium; accumulation in surface tissues; tear film instability; ocular surface cell apoptosis

Chlorobutanol

TobraDex ointment (tobramycin 0.3% and dexamethasone 0.1% sterile ophthalmic suspension and ointment, Alcon)

Detergent

Toxic effects take longer to manifest than BAK; does not affect stability of lipid component of tear film; extensive antimicrobial activity

Causes keratitis and irritation to ocular surface; decreased amount of mitoses to corneal epithelial cells; unstable when stored at room temperature

Cetrimonium chloride

Civigel (0.2% ophtalmic gel, Novartis)

Detergent

Excellent antiseptic qualities

Causes keratinization and inflammatory infiltrates at the limbus and within the conjunctival stroma and epithelium

Polyquaternium-1 (Polyquad)

Tears Naturale II (0.3% hydroxypropyl methylcellulose, 0.1% dextran 70, Alcon)

Opti-Free Express Disinfecting Solution (Alcon)

Detergent

Less toxicity to corneoconjunctival surface than BAK

Superficial corneal epithelial damage reduces density of conjunctival goblet cells

Edetate disodium (EDTA)

Acular (ketorolac tromethamine 0.5%, Allergan)

Betagan (levobunolol, Allergan)

Chelating agent

Inactivates trace amounts of heavy metals

Few studies documenting chronic side effects.

SofZia

Travatan Z (travoprost Z, Alcon)

Oxidative

Modified into harmless elements upon instillation; smaller amounts of conjuntivocorneal inflammation compared to BAK

Newer agent requiring more studies to understand ocular safety profile of the preservative independent of active ingredients.

Sodium perborate (GenAqua)

GenTeal (0.2% hydroxypropyl methylcellulose, Novartis)

Oxidative

Catalyzed into hydrogen peroxide, water, and oxygen upon instillation; activity against Aspergillus; less toxicity than BAK

Few studies documenting ocular tolerability and side-effect profile

Stabilized oxychloro complex (SOC/Purite)

Alphagan-P (brimonidine tartrate, Allergan)

Refresh Tears (0.5% carboxymethylcellulose, Allergan)

Oxidative

Dissociates into water, oxygen, sodium, and chlorine free radicals

As with SofZia, more studies are needed to assess ocular side effects independent of active ingredients

Benzalkonium chloride (BAK)

BAK is the most frequently used preservative in ophthalmic solutions today.7 It is currently found in more than 70% of multiuse preparations within ophthalmic medicine. The reasons for its widespread use are numerous. BAK has excellent efficacy in controlling microbial contamination within the medications, and its ability to break cell-cell junctions in the corneal epithelium allows for ophthalmic medicine to enter the anterior chamber. BAK is also one of the oldest preservatives used in ophthalmic medicines, so its familiarity in the industry is unprecedented.

While the efficacy of BAK is well known, there are a multitude of published studies that document the detrimental effects of BAK.3,8-11 Breakdown of the corneal epithelium and thus increased permeability of the cornea as a result of BAK toxicity is well documented.10 The induction of high concentrations of BAK within the ocular surface tissues through repeated exposure and subsequent accumulation reduces tear break-up time by causing disruption of the lipid component of the tear film.11

The concentration of BAK in glaucoma formulations ranges from 0.004% to 0.02%. BAK has been shown to stimulate necrosis (at concentrations of 0.05% to 0.1%) and cellular apoptosis (at concentrations of 0.01%) by way of disturbing the cellular membrane in bacterial cells.9 Conversely, human ocular surface cells can also absorb BAK, and the effects on human ocular surface cells are comparable to those seen in bacterial cells. The effects of the detergent are cumulative and become more severe with more concentrated and frequent exposures.9 On a genetic basis, repeated exposure to BAK can cause the overexpression of the cell marker Apo 2.7, which has been implicated in cellular apoptosis.8

Benzalkonium is classified as a detergent and quaternary ammonium compound with a broad range of antimicrobial activity. It was first introduced as a germicidal in the 1910s.12 In the ophthalmic industry, BAK was first used in the 1940s to preserve hard contact lens solutions. Since then, BAK has been used in nearly all classes of ophthalmic solutions, from anti-glaucoma medicines to over-the-counter artificial tear solutions.

Chlorobutanol

Chlorobutanol is a detergent preservative that was formerly used as an active ingredient in hypnotic and sedative agents.3 It has been used as a preservative agent in artificial tears, where it has been documented to cause significant keratitis and irritation to the ocular surface.13 Chlorobutanol does not, however, affect the stability of the lipid component of the tear film.14 Although it can damage the ocular surface cells, its toxic effects take longer to manifest in human corneas than do the effects of BAK.15 Human corneal epithelial cells exposed to chlorobutanol display decreased amount of mitoses and deterioration of overall cell integrity.15

Chlorobutanol has a broad antimicrobial spectrum.16 The extended use of chlorobutanol, however, has been limited in ophthalmic medicines because of the reasons noted above, and because it has a tendency to become unstable when stored at room temperature for extended periods of time.16

BAK and chlorobutanol are both detergent-type preservatives, but chlorobutanol does not act like a surfactant.14 Instead, its method of action is cell lysis by way of disruption of the microbial cell membrane lipid configuration.14

Cetrimonium chloride

Cetrimonium is a detergent-type preservative. Due to its antiseptic and cationic surfactant qualities, cetrimonium is used mostly as a softening agent in hair treatment products. It is also used as a preservative in antifungal crèmes, as a fermentation aid, and as a dispersant. Its ophthalmic uses include preservation of artificial tear solutions such as Civigel (0.2% ophtalmic gel, Novartis). Its corneoconjunctival cell toxicity has been deemed similar to BAK. Cetrimonium has also been shown to cause keratinization and inflammatory infiltrates at the corneal limbus and within the conjunctival stroma and epithelium.17

Polyquaternium-1

Polyquaternium-1 (Polyquad, Alcon) is a detergent-type preservative derived from BAK. Although it is a detergent, it is unique in that it is attracted by bacterial cells. Human corneal epithelial cells repel the Polyquad.18 It is the main ingredient in Tears Naturale II (0.3% hydroxypropyl methylcellulose, 0.1% dextran 70, Alcon) and Opti-Free Express Multi-Purpose Disinfecting Solution (Alcon), as well as other storage solutions for contact lenses.

Polyquad was formulated in the mid 1980s by Alcon as a preservative of contact lens storage solutions. It was developed because other preservatives (such as BAK) were known to become concentrated in contact lenses that had been stored in conventional lens solutions. When placed in an aqueous ocular environment, this acts as a reservoir of preservative that can later be released from the lens. Polyquad does not become concentrated in contact lenses, and it has been proven to be less toxic to the ocular surface cells than BAK.19 However, it can reduce the density of goblet cells within the bulbar conjunctiva, which decreases aqueous tear film production.19 It has also been proven to cause destruction of the superficial corneal epithelium.20

Edetate disodium (EDTA)

EDTA has preservative effects based on its ability to chelate. Ophthalmic solutions containing EDTA include Betagan (levobunolol, Allergan) and Acular (ketorolac tromethamine 0.5%, Allergan). When added to topical medicines in low concentrations, it has the propensity to inactivate trace amounts of heavy metals, which aids in the preservation of these formulations.16

In the medical field, it is used to remedy acute lead and mercury poisoning, as well as systemic hypercalcemia. Therapeutically, it is used to remove calcified plaques that take place in band keratopathy of the cornea.21 It has also been used in eye washes to aid in neutralization of calcium hydroxide or lime burns to the corneal surface.

As it is a chelating agent, EDTA can be used in a variety of non-ophthalmic products. These include hair conditioner, facial cleansers, aftershaves, and deodorants. In the recycling industry, it has been used to recover lead from used lead acid batteries.

Polyhexamethylene biguanide (PHMB)

PHMB has historically been a component of pool cleaners, skin disinfectants, and urinary catheter flush solutions. Its benefits against Acanthamoeba and bacteria are well known.22 It has been used in contact lens solutions such as ReNu (Bausch & Lomb) and has been shown to be non-irritating to human corneal cells. PHMB employs its microbial activity by integrating into bacterial cell walls, thereby disrupting its membrane. It has also been shown to lethally alter the transcription of bacterial DNA.23 However, its antifungal capabilities are limited.16

Sodium perborate

Sodium perborate is an oxidative preservative contained in GenTeal lubricant eye drops (0.2% hydroxypropyl methylcellulose, Novartis). Historically, sodium perborate has been use in dental hygiene solutions since the 1950s. When it was introduced in ophthalmic solutions, it was one of the first of the oxidative-type preservatives used.

Upon exposure to an aqueous environment, sodium perborate is catalyzed into hydrogen peroxide, water, and oxygen, which is a property exclusive to this compound. The hydrogen peroxide formed by this reaction effectively kills microbes.24 Another advantage is that it has excellent antimicrobial activity on Aspergillus niger.24 Sodium perborate alters protein synthesis within bacterial cells by oxidizing cell membranes and altering membrane-bound enzymes, causing enzymatic inhibition.

Stabilized oxychloro complex (SOC)

SOC is an oxidative-type preservative. It has become a component of several different types of artificial tear and anti-glaucoma preparations, including Alphagan-P (brimonidine tartrate, Allergan) and Refresh Tears (0.5% carboxymethylcellulose, Allergan). One of its derivatives, sodium chlorite, has been used in water purification systems since the 1940s.25 SOC was introduced into ophthalmic medicines in the mid 1990s under the trade name Purite.

Stabilized oxychloro complex has been proven to be well tolerated by human corneoconjunctival surface cells26 and lacks cytotoxicity in vivo.24 SOC’s antimicrobial effects are broad and include antibacterial, antifungal, and antiviral effects. Even at low concentrations (0.005%), its antimicrobial activity is broad,24 which was validated during a study in which SOC was dispensed to patients up to 8 times in one day.26

The chemical composure of SOC is a mixture of chlorine dioxide, chlorite, and chlorate.3 Upon exposure to light, SOC dissociates into water, oxygen, sodium, and chlorine free radicals.27 The chlorine free radicals are thought to inhibit microorganism protein synthesis within cells by way of glutathione oxidation, which causes microbe cell death.28

SofZia

SofZia is the newest development in the field of ophthalmic preservation systems. It is the preservative system contained in travoprost Z (Travatan Z, Alcon). Travoprost Z was developed as the first prostaglandin analogue to be preserved with something other than BAK.

The sofZia system effectively preserves the travoprost while it is being stored between uses. However, after travaprost Z is instilled within the eye, it becomes modified into innocuous elements.6 These elements are gentle on the ocular surface. When exposed to cations, such as those that are normally encountered in the tear film of the eye, sofZia is deemed inactive. This is thought to induce less cytotoxic effects to the ocular surface compared to more conventional preservatives. Travoprost with sofZia also induces smaller amounts of conjunctival inflammation and corneal changes than travoprost treated with BAK. In fact, it has been recently verified that sofZia-preserved travoprost induces similar corneoconjunctival changes to preservative-free artificial tears.29