GB2263063A - Anti ulcer composition for fish - Google Patents

Abstract

Compositions containing formaldehyde, a quaternary ammonium salt and a brominated alkanediol both having antibacterial activity are used in combatting ulceration in freshwater fish. Alkanediol is e.g. 2-bromo-2-nitropropane-1,3-diol commercially available as Myacides or Bronpols. Quaternary ammonium salt may be a benzalkonium chloride available as Morpan BC50.

Description

Composition for controllina ulceration in freshwater fish.

This invention relates to the control of ulceration in freshwater fish, in particular aquarium fish and pond fish especially those freshwater fish which are being kept in ornamental fish farms at wholesalers, retailers and in domestic ponds and aquaria.

Commonly acknowledged problems with freshwater fish which have been treated with varying degrees of success are bacterial problems such as mouth rot and fin rot, and fungal conditions such as cotton wool fungus. Techniques for controlling these conditions which have hitherto been employed have included the addition to the aqueous habitat for the fish of such substances as Malachite green, Methylene blue and Acriflavin. Such substances are to varying degrees regarded as carcinogens and are likely therefore to be restricted in their use in the future.

A number of potential active ingredients for use as alternatives have been identified. These have mostly been anti-microbial bactericides and bacteriostats which have already found other applications such as in water tower treatment, cosmetic preservatives etc. The number of such substances which can be used in aqueous habitats for fish is reduced when criteria such as cost, water solubility, stability, activity against the relevant group of pathogens and toxicity to fish are taken into account. In general, the active ingredients are used at relatively low levels and frequently it is designed to look at combinations of substances to provide full effectiveness against pathogens.

Fin rot and mouth rot are common mild bacterial problems caused by Aeromonas, Pseudomonas and mycobacteria, and cotton wool fungus is caused by Saprolegnia species. Anti fungal and anti bacterial treatments for solving such problems have hitherto been investigated in fish room trials taking into account the aforementioned criteria. Fish used in the above work also suffered from ulceration which has in recent years proved to be a severe problem affecting ornamental fish stock.

It is an object of the present invention to provide a composition showing effective anti ulcer action on freshwater fish in pond and aquarium habitats.

It has now been discovered that a combination of active ingredients which was undergoing evaluation particularly for anti-bacterial and anti-fungal activity has anti-ulcer character. Thus, according to the present invention, there is provided an aqueous composition for use in combatting ulceration in freshwater fish which comprises, in solution in water, or any water miscible non toxic solvent, a mixture of formaldehyde, a quaternary ammonium salt having bactericidal activity and a brominated alkanediol itself having anti bacterial activity.

The formaldehyde utilized in making up such compositions will generally be derived from formalin, that is aqueous formaldehyde solution having a formaldehyde concentration of about 37% to which 10 to 15 % of methanol has been added to prevent polymerization to para formaldehyde. Alternatively a formaldehyde donor may be substituted.

A wide range of quaternary ammonium compounds has bactericidal activity. The most common of these are benzalkonium salts of which benzalkonium chlorides are the compounds preferred for use in the practice of the present invention. The material which has been found to be particularly useful and which is readily available commercially is Morpan BC50 which is a 50% solution of alkybenzyl dimethylammonium chloride in water.

The third essential component of the compositions of the invention is the brominated alkanediol. A range of compounds which has been found to be the most suitable for this purpose is that of brominated nitroalkanediols, especially 2-bromo-2-nitropropane-1,3-diol available commercially in three grades of purity under the trademarks Bronpol, Myacide BT and Myacide AS. Any of these grades may be used but the current formulation uses Myacide As which is 95* pure. In general, however, it is possible to utilize any bactericidal water soluble brominated alkanediol preferably having 1 to 4 carbon atoms and whose water solubility is enhanced through its nitration.

The compositions of the present invention, although comprising known substances having bactericidal activity have been found to show a form of synergism which could not hitherto have been predicted. Using as it does relatively inexpensive readily available products, the composition of the present invention is relatively inexpensive and has been found surprisingly to be particularly effectively in the treatment of ulcerations as well as bacterial gill disease and systemic bacterial infections.

Although the three effective ingredients can be utilised in widely differing ratios, good results have been obtained when utilizing formalin solution (38% W/V), Morpan BC50 and Myacide AS in a ratio, V/V/W of 4 : 1 1.

The following examples illustrate the invention. In the examples the ingredients used were in the form of commercially available products identified hereinabove.

Hence, for each example there is provided data to indicate actual doses per indicated volume of water and active ingredient level (ai). All numerical values are in mg/l unless otherwise indicated.

Example 1 Two initial formulations each comprising Morpan BC50 and Myacide AS were used in combination with formaldehyde (Formulation la) or a formaldehyde donor substance (Nipaguard) (Formulation lib). The respective formulations were each tested for toxicology at varying levels of concentration of each component on Poecilia reticulata (Guppy) and Xiphorus helleri (Swordtail). It was found that the formula containing Nipaguard had a toxic effect at least three time that when employing pure formaldehyde with which overall there was 0% mortality.

Amount Amount!21 3x Required Dose ai aill ai/l Formulation la Horpan BC50 1.0 2 1.0 0.5 1.5 Myacide AS 0.5 1 1.0 0.5 1.5 FornaldehIde 13.0 26 9.1 4.55 13.65 ForGulation 1b Morpan BC50 1.0 2 1.0 0.5 1.5 Myacide AS 0.5 1 1.0 0.5 1.5 Nipaquard 10.0 20 3.0 1.5 4.5 Formulation for loom:: Formula la Formula 1b Morpan BC50 0.90 ml 0.90 ml Myacide AS 0.45 gm 0.45 gm Formaldehyde 11.70 ml Nipaguard 9.00 ml In each of Examples 2 to 6, there was used as formulation lc a modification of formulation la containing formaldehyde to provide the same concentrations of active ingredients in each case, the concentrations being as follows: Dose Amount/l ai/l Morpan BC50 1.0 mg/l 0.5 mg/l Myacide AS 0.5 mg/l 0.5 mg/l Formaldehyde 5.5 mg/l 1.925 mg/l Example 2 A 100 ml sample the formulation lc was tested for its toxicity against a mature biological filtration system (900 litres) containing various typical fauna and flora. The levels of ammonia, nitrite and nitrate were monitored over a short period of time.No control was used as the initial values of the nitrogenous parameters provided control information. It was found that the addition of the formaldehyde-containing composition had no deleterious effect on the various bacterial species required in transformation of ammonia to nitrate.

The actual amounts of active ingredients used were as follows: Formulation lc 100 ml sample (treat 900 ltr) Morpan BC50 0.90 ml Myacide AS 0.45 gm Formaldehyde 4.95 ml Example 3 Five Koi with an unknown internal systemic bacterial infection were placed in each of two 900 litre tanks.

One tank was to be supplied with an identical sample of formulation lc to that used in Example 2, while the other acted as a control. 100* mortality occurred in the control tank after five days whereas the fish present in the treated tank no longer showed erratic behaviour after five days and were seen to be showing behaviour typical of that of healthy fish.

Example 4 A field trial was carried out in a 4550 litre, centrally filtered holding system which was divided internally into four equal chambers each holding a single species of fish. A batch of 7.5 - 10 cm koi having an unknown systemic internal bacterial infection which was devastating the stock thereof was taken of which two fish were taken for pathology. Such fish were distributed in the tanks. The entire system was treated with a scaled up sample of formulation lc from that used in Example 2.

One chamber contained golden tench and a high mortality rate ensued; these fish were removed to a quarantine area. Two tench and two koi were taken to pathology after nine days. The mortality of the koi was seen to have been reduced dramatically as a result of the treatment. Pathology report showed that the typical protozoal parasites were present on the fish as well as a heavy infection of Aeromonas hydrophillia and Pseudomonas sp. After treatment no bacterial growth was found in either the tench or the koi and the protozoal parasites had been reduced dramatically. Subsequent toxicity tests showed a low toxicity of the compositions embodying the invention to golden tench. Therefore mortality in the above experiment must have been related to some other unrelated factor.

The amounts of active ingredients used were as follows: 200 ml samnle (treat 4550 ltr) Morpan BC50 4.550 ml Myacide AS 2.275 gm Formaldehyde 25.025 ml Example 5 Field trials were taken to the extent of a 600 litre aquatic pond environment using again the formaldehyde containing formulation of Examples 2 and 3 (formulation lc) appropriately scaled down. The purpose of the investigation was to establish the effects which the medication might have upon aquatic flora. Seven species of aquatic flora were initially present and only the weakest specimens of Mimulus sp. were found to be susceptible to the medication.

250ml sample (treat 600 ltr) Morpan BC50 0.60 ml Myacide AS 0.30 gm Formaldehyde 3.30 ml Example 6 The formaldehyde-containing formulation of Examples 2 and 3 was tested, under laboratory conditions in a 100 litre tank, and suitably scaled down, against ornamental goldfish having severe ulceration and fin rot by a direct comparison with a control group. One dose of the medication was supplied to the tank and observation continued for one week. During this period, it was noted that the severity of ulceration present in the test tank had decreased and by the end of the experiment tissue regeneration was well under way. In comparison, however, a control to which the formaldehyde-containing formulation was not supplied still showed severely inflamed cases of ulceration and fin rot.

The amounts of active ingredients used were as follows: 30ml sample (treat 100 ltr) Morpan BC50 0.10 ml Myacide As 0.05 gm Formaldehyde 0.55 ml Example 7 A field trial (21400 litre fresh water pond) was carried out against koi and golden orfe with an ulceration problem using the a further modification of the formulation of Example 1 containing formaldehyde (formulation Id). This was a double dose formulation with respect to the Morpan BC50 and Myacide AS. This formulation was also investigated for its effectiveness after being treated with sterilising ultraviolet radiation and in a multiple dose method of application.

Regeneration of the tissue of the ulcerated areas of the fish was found to have taken place after only ten days.

Moreover the medication was seen to be non toxic at the level used, even with multiple doses, to fish or nitrifying bacteria and it was seen that the presence of ultraviolet radiation does not reduce its activity in any way.

The active ingredient actual amounts and concentrations used were as follows: 2500ml sample Dose Fonoula 1d (treat 21500 ltr) Amount/l aill Morpan 8C50 42.8 ml 2.0 mg/l 1.0 mg/l Myacide AS 21.4 gm 1,0 mg.l 1.0 m/l Formaldehyde 117.7 ml 5.5 mg/l 1.925 mg/l

Claims (18)

Claims:

1. An aqueous composition for use in combatting ulceration in freshwater fish which comprises, in solution in water, a mixture of formaldehyde, a quaternary ammonium salt having antibacterial activity and a brominated alkanediol itself having antibacterial activity.

2. A composition as claimed in Claim 1 which comprises formalin as a source of the formaldehyde.

3. A composition as claimed in Claim 1 or 2, wherein the quaternary ammonium compound is a benzalkonium salt.

4. A composition as claimed in Claim 3, wherein the benzalkonium salt is a benzalkonium chloride.

5. A composition as claimed in Claim 4, wherein the benzalkonium chloride is an alkylbenzyl dimethyl ammonium chloride.

6. A composition as claimed in any preceding claim, wherein the brominated alkanediol is a brominated nitroalkanediol containing 1 to 4 carbon atoms.

7. A composition as claimed in Claim 6, wherein the brominated alkanediol is 2-bromo-2-nitropropane-1,3diol.

8. A composition as claimed in Claim 1 which comprises formalin solution (38% W/V), a 50t by weight of alkylbenzyl dimethyl ammonium chloride in water and 2bromo-2-nitropropane-1,3-diol in a ratio V/V/W of 4 : 1 1.

9. An aqueous composition for use in combatting ulcerations in freshwater fish, as claimed in Claim 1, substantially as recited in any one of the foregoing examples.

10. A method of treating a freshwater fish habitat to combat ulceration of fish therein which comprises adding to the habitat a mixture of formaldehyde, a quaternary ammonium salt having antibacterial activity and a brominated alkanediol itself having antibacterial activity.

11. A method as claimed in Claim 9 which comprises formalin as a source of the formaldehyde.

12. A method as claimed in Claim 9 or 10, wherein the quaternary ammonium compound is a benzalkonium salt.

13. A method as claimed in A composition as claimed in Claim 11, wherein the benzalkonium salt is a benzalkonium chloride.

14. A method as claimed in Claim 12, wherein the benzalkonium chloride is an alkylbenzyl dimethyl ammonium chloride.

15. A method as claimed in any preceding claim, wherein the brominated alkanediol is a brominated nitroalkanediol containing 1 to 4 carbon atoms.

16. A method as claimed in Claim 14, wherein the brominated alkanediol is 2-bromo-2-nitropropane-1,3-diol.

17. A method as claimed in Claim 9 which comprises formalin solution (38% W/V), a 50% by weight of alkylbenzyl dimethyl ammonium chloride in water and 2bromo-2-nitropropane-1,3-diol in a ratio V/V/W of 4 : 1 1.

18. A method of combatting ulceration in freshwater fish as claimed in Claim 10, substantially as described in any one of the foregoing examples.