WO1991003936A1

WO1991003936A1 - Effervescent compositions

Info

Publication number: WO1991003936A1
Application number: PCT/GB1990/001423
Authority: WO
Inventors: Thomas Ralph Auchincloss
Original assignee: Auchincloss Thomas R
Priority date: 1989-09-15
Filing date: 1990-09-14
Publication date: 1991-04-04
Also published as: CZ278433B6; SK278516B6; HRP920313A2; SI9011740A; YU174090A; SK449890A3; PL164970B1; CZ449890A3; GB8920973D0; PL286901A1

Abstract

An effervescent particulate biocidal, and in particular virucidal, composition comprising: a water-soluble inorganic halide, a strong oxidising agent which, in aqueous solution, reacts with the halide to generate hypohalite ions, sufficient sulphamic acid to act as a halogen acceptor, a water-soluble carbonate or bicarbonate, and sufficient excess sulphamic acid to react in water with the carbonate/bicarbonate to produce carbon dioxide and hence the required effervescence.

Description

EFFERVESCENT COMPOSITIONS Background of the Invention

1. Field of the Invention

This invention relates to biocidal, and in particular virucidal, preparations, and concerns specifically such preparations in the form of effervescent tablets.

2. Description of the Prior Art

Hypochlorites, in the form of liquid sodium hypochlorite ( domestic bleach) ) or calcium hypochlorite (bleaching powder), and materials such as trichlorocyanuric acid and Chloramine T, have been in use for many years as bleaching and sanitising agents for domestic, industrial and to a lesser extent farm use. These products are marketed as powders and liquids - principally powders - and have a pH in use ranging from 7 to 11. They all suffer from drawbacks. Thus, liquid products are corrosive, unstable and readily inactivated by organic matter, so limiting their usefulness and reliability, particularly under farm conditions, where large quantities of organic matter are encountered. Powder products are more stable, but are much less reactive. Chloramine T, for example, requires extremely high concentrations to produce an acceptable biocidal effect, and in addition its activity is seriously affected by organic matter. Because the products are offered in alkaline or neutral formulations their virucidal activity is severely restricted. Today in human and animal health situations it is recognised that the first objective of any disinfectant should be to inactivate virus particles, which by and large, are the primary challenge to humans and livestock, resulting ultimately in secondary bacterial infections. For this purpose the ideal oxidising system ought to be acidic in nature, and at an in-use dilution should most preferably give a solution with a pH around 2 to 3. However, all hypochlorite solutions over this range of pH liberate chlorine gas from the hypochlorite source, and therefore it has not conventionally been possible to date to obtain these enhanced microbiocidal, particularly virucidal, properties.

There is extensive Prior Art dealing with formulations which set out to achieve stable acidic systems, specifically DuPont's GB

Patent number 932,750. Formulations made in accordance with this Patent are, however, found to be highly unstable in the powder state, and to liberate chlorine gas within a short period of manufacture. This is due principally to the use of high concentrations of sodium bisulphate and mineral acid salts added to achieve the desired level of acidity. The use of mineral acid boosters, beside introducing instability into the formulation, also causes the formulation to be highly corrosive.

Another disclosure is the present inventor's GB Patent number 2,078,522 which seeks to overcome the deficiencies found in the

DuPont Patent by using the minimum level of sulphamic acid as a chlorine acceptor and achieving the desired level of acidity at in- use dilution by using as an acid booster a non-reducing organic acid such as malic or succinic or, alternatively, an acid phosphate salt in combination with the sulphamic acid. This produces a relatively stable powder system which neither liberates chlorine gas when stored for prolonged periods at 37ºC, nor liberates chlorine (as detected by odour and visual examination) when the product is dissolved in water at the approved, appropriate dilutions. However, chlorine may be liberated if the product is stored in damp conditions, or if instructions are not followed and concentrated solutions are made up, and a disclosure that seeks to deal with that problem is that of the present Applicant's GB Patent number 2, 164, 851, where the hypochlorite is replaced by a mixture of an inorganic chloride and an oxidising agent, which mixture generates hypochlorite ions in aqueous solution. In the present Applicant's GB specification number 2,187,098. there is disclosed a yet further improved version, the improvement residing in the careful control of the amounts of the composition's various ingredients. This specification discloses a dry, particulate, water-soluble biocidal composition comprising: 0.01 to 5 parts by weight of a water-soluble inorganic halide;

25 to 60 parts by weight of an oxidising agent which, in aqueous solution, reacts with the halide to generate hypochlorite ions; 3 to 8 parts by weight of sulphamic acid; up to 20 parts by weight of a non-reducing organic acid; and

10 to 30 parts by weight of an anhydrous alkali-metal phosphate; the pH of a 1% by weight aqueous solution of the composition being between 1.2 and 5.5.

Such compositions have proven particularly useful, but there are occasions when their physical form - that of a dry, particulate (powder-like ) material - is not as convenient as it might be. For example the phenomenon of "dusting" is well known whereby the powder gives a primary irritant effect which can cause eye damage, etc.

It is therefore common practice to produce powder compositions in tablet form. This has several advantages, e.g. accurate measured dosage, avoidance of "dusting", centralised easy no-weigh dispersing, and ease of stock control and usage control. The principal use of such tablets is in hospitals because in the medical field there is a particularly great need for accurately measured dosage presentation.

It is difficult, however, to achieve within the relatively small size of a tablet, the concentrated high levels of biocidal activity necessary to combat the kinds of wide-spectrum virucidal infections occurring worldwide today. The conventional way to make tablets is to use (for example) citric acid plus a bicarbonate to get the required effervescence. This works well but it gives a relatively large tablet. Not only is this difficult for small animals, for example poultry, to swallow directly, it also takes far longer than is desirable to dissolve if it is added to the chickens drinking water as well as or instead of being mixed directly with their dry food.

The use of (for example) adipic acid gives a faster solubility but leaves an unpleasant residue which is unacceptable in, for example, medical situations. It is conventional to incorporate within the formulation reagents which react together, when the tablet is placed in water, to generate carbon dioxide gas - to effervesce. This effervescent reaction assists in the disintegration of the tablet, and in the solubilisation of the other tablet ingredients. Typical reagents which are chosen for this purpose are sodium bicarbonate and an organic acid, for example citric, adipic or tartaric acid. However, when these organic acids are employed the sodium salts formed by the reaction - the citrates, adipates or tartrates - being weak acid salts of a strong base, function as buffering agents, stabilising the solution's pH at a (preferably) relatively high value, and accordingly it is not possible to obtain solutions which have the low pH which, as explained above, is of particular importance virologically.

The present invention makes it possible to produce these biocidal, but essentially wide-spectrum preparations in the form of a tablet which, on being dissolved in water, provides a solution having a low pH, there by employed not an organic acid (such as citric, etc) but instead the inorganic acid sulphamic acid (NH₂.SO₃H).

Despite the fact that this use of sulphamic acid is clearly contrary to the teachings of the aforementioned earlier specifications, which have required the amount of sulphamic acid to be reduced (so as still to act as a chlorine acceptor but not to cause the dry composition to be unstable), it has surprisingly been found that a suitable excess of sulphamic acid together with a carbonate or bicarbonate provides an effervescent composition suitable for tableting but still exhibiting the desired stability with respect to chlorine liberation and biocidal activity.

Summary of the Invention

A tabletable effervescent particulate biocidal, and in particular virucidal, preparation which includes water-soluble inorganic halide, strong oxidising agent which, in aqueous solution, reacts with the halide to generate hypohalite ions, sufficient sulphamic acid to act as a halogen acceptor, a water-soluble carbonate or bicarbonate, and sufficient excess sulphamic acid to react in water with the carbonate- bicarbonate to produce carbon dioxide and hence the required effervescence.

Detailed Description of the Inventive Concept

The preferred inorganic halide is sodium chloride, with the preferred range of amounts being from 0.01 to 5 parts by weight, especially from 0.2 to 2 parts by weight when the composition is to be dissolved in water from the normal domestic water supply. However, other halides can be used - for example, potassium chloride, bromide or iodide, or sodium bromide or iodide. The oxidising agent, which is advantageously employed in an amount of from 25 to 60 parts by weight, is conveniently a persulphate or peroxyphthalate (particularly potassium monoperoxyphthalate). The preferred oxidising agent is, however, the commercially-available potassium persulphate triple salt approximately represented by 2 KHSO₅.KHSO_4. K₂SO₄ (in weight terms 45:25:30).

Other oxidising agents can be used in amounts equivalent in terms of available oxidising power. The oxidising power of products of this kind is conveniently measured in terms of the amount of iodine liberated by reaction with potassium iodide (determined by a subsequent titration of that iodine). The procedure is standard in the Art, and the results can be expressed in terms of available hypohalite, of halogen, or of oxygen, or simply as "oxidising power". The carbonate or bicarbonate is conveniently employed in an amount of from 2 to 25 parts by weight, and of the many typical carbonates and bicarbonates the alkali-metal bicarbonate sodium bicarbonate is typically satisfactory.

The sulphamic acid is used both as a halogen acceptor and as an acid to react with the carbonate/bicarbonate to generate carbon dioxide. As the halogen acceptor there is desirably from 3 to 8 parts by weight, while as the carbon dioxide generator there is preferably an additional 7 to 12 parts by weight (the whole amount thus adding to from 10 to 20 parts by weight). To improve its tableting properties the effervescent composition of the invention may contain a binder capable of loosely bonding the particles together when compressed in a tablet press. The amount of binder used is preferably of the order of 0.5 to 2 parts by weight, and suitable binders are sodium stearate (a fatty acid soap) and a polyoxyethylene (a polyglycol), and mixtures of the two.

It will be seen that in a preferred aspect the invention provides a dry, effervescent, particulate water-soluble virucidal composition comprising: 0.01 to 5 parts by weight of a water-soluble inorganic halide;

25 to 60 parts by weight of an oxidising agent which, in aqueous solution, reacts with the halide to generate hypohalite ions; 5 to 25 parts by weight of a water-soluble carbonate or bicarbonate;

10 to 20 parts by weight of sulphamic acid; and a bonding agent; the pH of a 1% by weight aqueous solution of the composition lying between 1.0 and 5.0, preferably between 1.2 and 4.0.

To improve various other of its properties, the effervescent composition of the invention may contain a number of additional components, specifically an anhydrous alkali-metal phosphate (preferably from 10 to 30 parts by weight), a non-reducing organic acid (preferably up to 20 parts by weight), and an anhydrous surfactant (preferably up to 20 parts by weight). The alkali metal phosphate may be sodium hexametaphosphate (also known as sodium polyphosphate). Other phosphates, which can be used to replace all or part of the sodium hexametaphosphate, include tetrasodium pyrophosphate, and the corresponding potassium compounds. The phosphates act as buffering and chelating agents, in combination with the flat pH curve of sulphamic acid, and enable the composition to be effective over a wide range of in-use conditions - for example, the composition can be dissolved in hard water without deleteriously affecting its virucidal properties. A non-reducing organic acid may be defined as an organic acid that does not reduce the oxidising power of a 1% aqueous solution of a test mixture of 50 parts by weight of the potassium persulphate triple salt referred to above, 45 parts by weight of sodium chloride and 5 parts by weight of sulphamic acid (with the addition of 20 parts by weight of the test acid, when left for thirty minutes). The preferred organic acids are malic acid and succinic acid.

Any surfactant compatible with the acids and oxidising agents can be utilised but a particularly effective surfactant has been found to be sodium dodecylbenzene sulphonate. Other suitable surfactants include lauryl ether sulphates, ethylene oxide/propylene oxide alkyl phenol condensates, polyglycol ethers of fatty alcohols, fatty acid ethylene oxide condensates, polyglycol ethers of alkyl phenols, and fatty alcohol ethoxylates. The incorporation of a surfactant in the composition gives the important advantage, particularly at high surfactant levels, of enabling cleaning and disinfecting in a single operation. The effervescent compositions of this invention are for tableting, and they may be made into tablets using any suitable tableting technique. Thus, they may be supplied to the dies of a tableting press, and there compressed into tablet form. In principle this is all perfectly conventional, and no more need be said about it at this time, save that the invention naturally extends to the compositions in tablet form.

The formed tablets may be added to water at the point of use to form a disinfectant, biocidal aqueous composition of the required concentration preferably immediately prior to use. The presence of the phosphate in the composition contributes to the extended useful life of the aqueous preparation, and improves the effectiveness of the composition when dissolved in hard water (the phosphate causes sequestration of any metal ions which might cause rapid decomposition of the oxidising agents present in the solution).

The aqueous preparation is a broad spectrum biocide. Although the method of viral degradation is not known, it is believed that the lipoprotein cytoplasmic membrane or outer lipid protective layer of the virus is first disrupted thereby exposing the RNA or

DNA nucleus of the virus. The sulphamic acid acts as a chlorine acceptor to retain nascent chlorine in solution as an addition product with the sulphamic acid thereby avoiding the evolution of chlorine gas. Maintenance of a low chloride or other halide concentration assists in this prevention of chloride evolution without reducing the bactericidal efficacy of the composition.

In the aforementioned specification number 2,187,098 details are given of the virucidal activity of a composition of that specification. Tests have indicated that the incorporation of carbonate or bicarbonate , additional sulphamic acid and bonding agent has no significantly adverse effect on the bactericidal activity Example 1: Preparation of effervescent virucidal tablets

Stage A: Preparation of a virucidal composition according to the

aforementioned Patent specification No. 2 ,187,098

A virucidal composition was prepared by mixing together the following ingredients (the amounts are in parts by weight):

Sodium chloride 1.5

Potassium persulphate (triple salt) 50.0

Sulphamic Acid 5.0

Malic Acid 10.0

Sodium hexametaphosphate 18.5

Sodium dodecylbenzene sulphonate 15.0

The potassium persulphate triple salt is that referred to hereinbefore. It has a minimum active oxygen content of 4.5%. The sodium hexametaphosphate is also known as sodium polyphosphate, and is used in powdered or granulated form.

The composition was prepared by first mixing together the phosphate and the sulphonate, followed by the addition of the persulphate and the acids and finally, the sodium chloride. A 1% by weight solution of the composition in de-ionised water has a pH of 2.4.

Stage B: Preparation of tablets

An effervescent formulation was prepared by mixing together the following ingredients (the amounts are in grams):

The above-prepared virucidal composition

of the aforementioned specification

number 2,187,098 250

Sodium bicarbonate 34

Sulphamic Acid 31

Sodium stearate 10

Polyoxyethyleneglycol 23

The composition was prepared as a dry powder mix, and then formed into 100 tablets using conventional tableting techniques. The sodium stearate and polyoxyethyleneglycol together function as a binder. When the tablets are dropped into water an effervescent reaction occurs, with the generation of carbon dioxide. The effervescent reaction assists in the disintegration and solubilisation of the tablet.

When a tablet is placed in an amount of tap water sufficient to produce a 1% by weight solution of the composition, the pH of the solution is 2.6.

Tests have been carried out to establish the virucidal activity of the various compositions of the invention in accordance with the standard Test Procedures of the United Kingdom (GB) Ministry of Agriculture, Fisheries and Food (MAFF) and of the (GB) Animal

Virus Research Institute (AVRI). These tests have shown the effectiveness of the compositions against the following broad spectrum of viruses and viral infections. Thus, at the dilutions quoted in the Table below, the composition of Example 1 gave a log 4 reduction in virus titre TABLE

Virus family Viral infection Dilution Adenoviridae Egg drop syndrome 1: 100 Herpefcoviridae Infectious bovine

rhinotracheitis 1:600

Aujeszky's Disease 1:280

Feline herpes 1:200

Iridoviridae African swine fever 1: 200 Parvoviridae Canine parvovirus 1:50 Poxviridae Pseudo cowpox 1:300 Coronaviridae Transmissable

gastro-enteritis 1:450

Avian infectious

bronchitis 1:280

Canine coronavirus 1: 100

Orthomyxoviridae Avian influenza 1:320

Paramyxoviridae Newcastle disease 1:280

Distemper 1:280

Picornaviridae Swine vesicular Disease 1:200

Foot & mouth disease 1: 1300

Reoviridae Gumboro (IBD) 1:250 Retroviridae Maedi & Visna 1:400

AIDS 1:200

Rhabdoviridae Rabies 1:280 Togaviridae Equine arteritis 1:350 These results are the same as those set out in the aforementioned Specification number 2,187,098, indicating that formulating the composition as an effervescent one does not deleteriousiy affect its bactericidal activity. Tests have also been carried out to assess both the short and the long term stability of the tableted dry mixed effervescent compositions. In these a quantity of each composition was stored at 37ºC in a sealed container, and sampled periodically. Typical results for the composition of the Examples hereinbefore are as follows:

oxidising power expressed

Time as % available chlorine - for

(days) Composition of Example:

1

0 10.42

2 10.38

4 10.44

7 10.37

14 10.45

21 10.50

28 10.41

The variations in the percentage available chlorine are within the range of anticipated experimental error, and indicate excellent short-term stability.

The order of mixing specified at page 10, lines 16 to 20 above is particularly important if the subsequent aqueous solution is to act with its maximum potential effect as a wide-spectrum biocidal, particularly virucidal, disinfectant.

Claims

CLAIMS:

1. An effervescent particulate biocidal, and in particular virucidal, composition comprising: a water-soluble inorganic halide, a strong oxidising agent which, in aqueous solution, reacts with the halide to generate hypohalite ions, sufficient sulphamic acid to act as a halogen acceptor, a water-soluble carbonate or bicarbonate, and sufficient excess sulphamic acid to react in water with the carbonate/bicarbonate to produce carbon dioxide and hence the required effervescence.

2. A composition according to Claim 1 and comprising:

0.01 to 5 parts by weight of a water-soluble inorganic halide; 25 to 60 parts by weight of an oxidising agent which, in aqueous solution, reacts with the halide to generate hypohalite ions;

5 to 25 parts by weight of a water-soluble carbonate or bicarbonate; 10 to 20 parts by weight of sulphamic acid; and a bonding agent; the pH of a 1% by weight aqueous solution of the composition lying between 1.0 and 5.0, preferably between 1.2 and 4.0.

3. A composition according to Claim 1 or Claim 2 and in which the inorganic halide is sodium chloride present in amounts of from 0.1 to 5 parts by weight.

4. A composition according to any of the preceding Claims and further comprising an anhydrous alkali-metal phosphate

(preferably from 10 to 30 parts by weight), a non-reducing organic acid (preferably up to 20 parts by weight), and an anhydrous surfactant (preferably up to 20 parts by weight).

5. A tabletable effervescent biocidal composition as described in Example 1 herein.