SI9011740A - Effervescent compositions - Google Patents

Abstract

Particulate effervescent compound biocidal, in particular a virucidal preparation comprising: water-soluble inorganic halide, a powerful oxidizing agent found in aq the solution reacts with the halide to form hypohalite ions, enough sulfamic acid to work as a halogen acceptor, water soluble carbonate or bicarbonate and a sufficient excess of sulfamic acid, yes reacts in water with carbonate / bicarbonate whereby carbon dioxide is formed and thus the necessary foaming.

Description

SUSPECTED PREPARATIONS

1. FIELD OF THE INVENTION

The present invention relates to biocidal products, in particular to virucidal preparations, and in particular to said preparations in the form of effervescent tablets.

2. Description of the prior art

Hypochlorites in the form of liquid sodium hypochlorite (household bleaching fluid) or calcium hypochlorite (bleaching powder) and substances such as trichlorocyanum acid and Chloramine T have been used for many years as household bleaching and disinfection agents in industry, and on a smaller scale on farms. These products are commercially available as powders and liquids - mainly powders - and have a pH in the range of 7 to

11. They all have flaws; thus, liquid products are corrosive and unstable and easily inactivated by organic matter, thus limiting their usefulness and reliability, especially under conditions that govern farms where large quantities of organic matter are present. Powder products are more stable but much less reactive. For example, Chloramine T requires extremely high concentrations to achieve an acceptable biocidal effect, and its activity is significantly influenced by organic matter.

Because these products are available in alkaline or neutral formulations, their virucidal activity is very limited. Today, in the human and animal health field, the primary goal of any disinfectant is to inactivate the viral particles, which are the primary agents in humans and livestock, and this infection is ultimately followed by bacterial infections. For this purpose, the oxidation system should be acidic in nature and dilution for use should give a solution with a pH of about 2 to 3. However, all hypochlorite solutions in this pH range release gaseous chlorine from hypochlorite origin, and thus, it has not been possible to achieve these improvements microbiocidal and especially virucidal properties.

The state of the art in the preparation of compositions for the preparation of stable acidic systems is very extensive, and is particularly described in DuPont GB patent no. 932,750. However, the formulations prepared in accordance with this patent are very unstable in the powder state and release chlorine gas over a short production time. This is mainly due to the use of high concentrations of sodium bisulphate and salts of mineral acids, which are added to achieve the desired acidity level. The use of mineral acids in addition to introducing instability into the formulation also makes the formulation highly corrosive.

The second published document is the inventors' English patent no. GB 2,078,522, which attempts to overcome the disadvantages of DuPont's patent by using a minimum level of sulfamic acid as a chlorine acceptor and achieving the desired acidity level by dilution using non-reducing organic acid e.g. malic or succinic acids or alternatively acidic phosphate salts in combination with sulfamic acid as an acid additive. This results in a relatively stable powder system that neither releases gas chlorine during long-term storage at 37 ° C, nor releases chlorine (determined by odor or by visual inspection) by dissolving the product in water at approved appropriate dilutions. However, chlorine release may occur if the product is stored in humid conditions or if the instructions are followed and concentrated solutions are prepared; The document attempting to solve this problem is the applicant's English patent no. GB 2,164,851, in which hypochlorite is replaced by a mixture of inorganic chloride and an oxidizing agent, that is, a mixture which releases hypochlorite ions in aqueous solution. In the applicant's patent no. GB 2,187,098 describes a further improved version wherein the improvement is represented by a careful control of the amounts of the various constituents of the preparation. This specification describes a dry, water-soluble biocidal product comprising:

0.01 to 5 parts by weight of water-soluble inorganic halide;

up to 60% by weight of oxidizing agent reacting with halide in aqueous solution to release hypochlorite ions;

up to 8 parts by weight of sulfamic acid;

up to 20 parts by weight of non-reducing organic acid; and up to 30 parts by weight of anhydrous alkali metal phosphate;

and whose pH is 1% by weight of the aqueous solution being between 1.2 and 5.5.

Such preparations have proven to be particularly useful, but there are situations where their physical form - a dry, particulate material (powder) material is not as appropriate as it could be. For example, the phenomenon of dusting, in which the powder produces a primary irritant effect that can cause eye damage, etc., is well known.

It is therefore common practice for powder preparations to be produced in tablet form. This has some advantages, such as fine-tuned dosing, avoiding dusting, centralized easy dispersion and easy storage and use control. The main use of such tablets is in hospitals because there is a particularly high need for meticulously accurate dosing in the medical field.

However, in the relatively small size of the tablet, it is difficult to achieve the concentrated high levels of biocidal activity required to combat the types of broad-spectrum viral infections that are prevalent today. The usual way of making tablets is to use (for example) citric acid and bicarbonate to achieve the foaming required. This works fine but gives a relatively large tablet. For small animals such as poultry, it is not only difficult to swallow directly, it also takes much longer than desired to dissolve if it is either added to the chickens in drinking water instead of mixed with their dry food or removed. directly with their dry food.

The use of (for example) adipic acid results in faster dissolution but leaves an unpleasant residue which is not acceptable in for example medical situations.

It is customary to include reagents in the formulation that react with each other when the tablet is placed in water, releasing gaseous carbon dioxide - foaming occurs. This foaming reaction assists in the breakdown of the tablet and in the solubilization of other components of the tablet.

Typical reagents selected for this purpose are sodium bicarbonate and organic acid, for example citric, adipic or tartaric acid. However, when these organic acids are used, the sodium salts formed in the reaction - citrates, adipates or tartrates - are weak acid salts with strong bases, act as buffers and stabilize the pH of the solution at (above all) a relatively high value and therefore cannot be obtained solutions that would have a low pH, which, as discussed above, is virologically particularly important.

The present invention enables the production of these substantially broad spectrum biocidal products in the form of tablets, which, after dissolution in water, yield a solution of low pH, using not organic acid (such as citric, etc.) but inorganic acid sulfamic acid (ΝΗ). ^ -ΞΟβΗ).

Despite the fact that this use of sulfamic acid is in clear contrast to the teaching of the aforementioned patents, which required that the amount of sulfamic acid should be reduced (so that it still acts as a chlorine acceptor but does not cause instability of the dry preparation), we surprisingly found that a suitable excess amount of sulfamic acid together with carbonate or bicarbonate gives an effervescent preparation suitable for tabletting but which still has the desired stability with respect to chlorine release and biocidal activity.

Summary of the Invention

An effervescent, particulate compound biocidal and in particular a tabletable virucidal preparation containing a water-soluble inorganic halide, a powerful oxidizing agent that reacts with the halide in aqueous solution, releasing hypohalite ions, sufficient sulphamic acid to act as a halogen acceptor , water-soluble carbonate or bicarbonate and a sufficient excess of sulfamic acid to react with carbonate-bicarbonate in water to produce carbon dioxide to produce the required foaming.

A detailed description of the inventive concept

Preferred inorganic halide is sodium chloride with a preferred quantitative range of 0.01 to 5 parts by weight, in particular from 0.2 to 2 parts by weight, when the preparation is intended for dissolution in household water. Of course, other halides may also be used - for example potassium chloride, bromide or iodide or sodium bromide or iodide.

A suitable oxidizing agent used primarily in the amount of 25 to 60 parts by weight is persulfate or peroxyphthalate (especially potassium monoperoxyphthalate). A preferred oxidizing agent is the commercially available triple salt of potassium persulfate, which is approximately represented as KHSC ^ -KHSO / pK ^ SC ^ (in a weight ratio of 45:25:30).

Other oxidizing agents may be used in amounts equivalent to the available oxidizing strength. The oxidative strength of such products is usually measured as the amount of iodine released upon reaction with potassium iodide (determined by titration of the iodine released). This process is standard in the art and the results can be expressed as available hypohalite, halogen or oxygen, or simply as oxidative strength.

Carbonate or bicarbonate are suitably used in an amount of 2 to 25 parts by weight, of which many typical carbonates and bicarbonates typically meet the requirements of alkali metal bicarbonate - sodium bicarbonate.

Sulfamic acid is used as a halogen acceptor and as an acid that reacts with carbonate / bicarbonate to produce carbon dioxide. As a halogen acceptor, 3 to 8 parts by weight are desirable, while an additional 7 to 12 parts by weight of carbon dioxide is desirable (the total amount is from 10 to 20 parts by weight).

In order to improve tableting properties, the effervescent formulation according to the invention may contain a binder that is able to gently bind particles during compression in the tablet. The amount of binder used is preferably in the order of 0.5 to 2 parts by weight, and suitable binders are sodium stearate (fatty acid soap) and polyoxyethylene (polyglycol), and mixtures of both.

It will be appreciated that in a preferred aspect, the invention provides a dry, effervescent, particulate composition comprising:

0.01 to 5 parts by weight of water-soluble organic halide;

up to 60% by weight of oxidizing agent reacting with halide in aqueous solution to form hypohalite ions;

up to 25 parts by weight of water soluble carbonate ah bicarbonate;

up to 20 parts by weight of sulfamic acid; and the binder;

The pH of 1% by weight of the aqueous solution of the preparation is between 1.0 and 5.0, preferably between 1.2 and 4.0.

In order to improve its various other properties, the effervescent preparation of the invention may comprise a number of additional components, in particular anhydrous alkali metal phosphate (preferably 10 to 30 parts by weight), non-reducing organic acid (preferably up to 20 parts by weight) and anhydrous surfactant (preferably up to 20 weight parts).

Alkali metal phosphate may be sodium hexametaphosphate (also known as sodium polyphosphate). Other phosphates that can be used to replace all or part of the sodium hexametaphosphate include tetranitrium pyrophosphate and the corresponding potassium compounds.

Phosphates act as buffering and chelating agents in combination with a flat pH curve of sulfamic acid and allow the preparation to be effective over a wide range of conditions - for example, it can be dissolved in hard water without adversely affecting its virucidal properties.

Non-reducing organic acid can be defined as an organic acid that does not reduce the oxidizing power of 1% aqueous solution of the test mixture composed of the 50 parts by weight of the triple salt of potassium persulfate mentioned above, 45 parts by weight of sodium chloride and 5 parts by weight of sulfamic acid (with the addition of 20 by weight of test acid when allowed to stand for thirty minutes). Preferred organic acids are malic and succinic acid.

Any surfactant that is compatible with acids and oxidizing agents can be used, and sodium dodecylbenzene sulfonate has proven to be a particularly effective surfactant. Other suitable surfactants include lauryl ether sulfates, ethylene oxide / propylene oxide and alkyl phenol condensates, polyglycolic fatty alcohol ethers, fatty acid and ethylene oxide condensates, polyglycolic alkyl phenol ethers and fatty alcohol ethoxylates. The incorporation of surfactants into the preparation achieves a significant advantage, especially at high levels of surfactants that allow for purification and disinfection with a single operation.

The effervescent compositions of the present invention are suitable for tabletting and can be formulated into tablets using any suitable tableting technique. Thus, they can be filled into tablet pellets, where they are compressed into tablet form. In principle, all this is usual, and nothing needs to be added here, except that the invention also includes tablet formulations.

The formulated tablets can be placed in water when used to obtain the disinfectant, biocidal aqueous preparation of the required concentration, preferably immediately before use. The presence of phosphate in the preparation contributes to the prolongation of the useful durability of the aqueous preparation and improves the efficiency of the preparation when dissolved in hard water (phosphate binds any metal ions present which could cause rapid decay in the solution of oxidizing agents present).

The aqueous preparation has a wide biocidal spectrum. Although the course of virus degradation is unknown, it is thought that the lipoprotein cytoplasmic membrane or the outer lipid protective layer of the virus is first degraded, revealing a nucleus formed by RNA or DNA. Sulfamic acid acts as a chlorine acceptor to retain nascent chlorine in solution as an additive product with sulfamic acid to prevent the development of chlorine gas. Maintaining a low concentration of chloride or other halide helps prevent chlorine from developing without reducing the bactericidal effectiveness of the preparation.

In the aforementioned patent no. No. 2,187,098 details of the virucidal activity of the preparation of this patent are provided. Tests have shown that the incorporation of carbonate or bicarbonate, additional sulfamic acid and a binder does not have a significant adverse effect on bactericidal activity.

Example 1: Preparation of effervescent virucidal tablets

Step A: Preparation of the virucidal preparation according to the aforementioned patent no, 2.187.098

The virucidal preparation was prepared by mixing the following ingredients (quantities are given in parts by weight):

Sodium chloride 1.5

Potassium persulfate (triple salt) 50.0

Sulfamic acid 5.0

Malic acid 10.0

Sodium hexametaphosphate 18.5

Sodium dodecylbenzene sulfonate 15.0

Potassium persulfate triple salt is the one mentioned earlier. It has a minimum 4.5% active oxygen content. Sodium hexametaphosphate is also known as sodium polyphosphate and is used in powdered or granular form.

The preparation was prepared by first mixing phosphate and sulfonate, then adding persulfate and acids and finally sodium chloride. 1 wt% solution of the preparation in deionized water has a pH of 2.4.

Level B: Tablet preparation

The summary formulation was prepared by mixing the following ingredients (quantities are given in grams):

The above virucidal preparation according to the aforementioned patent is 2,187,098 250

Sodium bicarbonate 34

Sulfamic acid 31

Sodium stearate 10

Polyoxyethylene glycol 23

The preparation was prepared as a dry powder mixture and then molded into 100 tablets using conventional tableting techniques. Sodium stearate and polyoxyethylene glycol work together as a binder.

When the tablets are lowered into water, a foaming reaction occurs with the release of carbon dioxide. Foaming and gas release help to break up and dissolve the tablet.

If the tablet is supplied with sufficient tap water to give a 1% solution by weight of the preparation, the pH of the solution is 2.6.

In order to determine the virucidal activity of various compositions of the present invention, tests were performed according to standard testing procedures of the British (GB) Ministry of Agriculture, Fisheries and Food (MAFF) and (GB) of the Institute for Virus Research (AVRI). These tests showed the effectiveness of the compounds against the next wide variety of viruses and viral infections. Thus, for the dilutions listed in the table below, the preparations of Example 1 resulted in a log 4 decrease in viral titer.

TABLE

The virus family Viral infection Thinning Adenoviridae egg drop syndrome 1: 100 Herpetoviridae 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 chickenpox (cowpox) 1: 300 Coronaviridae transmissible gastro-enteritis 1: 450 avian infectious bronchitis 1: 280 canine coronavirus 1: 100 Orthomyxoviridae avian influenza 1: 320 Paramyxoviridae Newcastle disease 1: 280

canine plague: 280

Picomaviridae swine vesicle disease 1: 200 boelzen feet and mouth 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 mentioned in the aforementioned patent 2,187,098, which indicates that the formulation of the preparation as an effervescent preparation has no adverse effect on its bactericidal activity.

We also performed tests to test both the short-term and long-term stability of tablet dry mixed effervescent preparations. In these tests, each preparation was stored at 37 ° C in a sealed container and periodically sampled. Here are typical results for the preparations in the Examples above:

Time oxidative strength expressed as% of available chlorine for the preparation of Example:

2_3

0 10.42 2 10.38 4 10.44 7 10.37 14 10.45 21 10.50 28 10.41

Differences in the percentage of available chlorine are within the range of experimental error expected and indicate excellent short-term stability.

Claims (5)

Claims: 1. Particulate effervescent composite biocidal product, and in particular a virucidal preparation, characterized in that it contains: water-soluble inorganic halide, a powerful oxidizing agent that reacts with the halide in aqueous solution to produce hypohalite ions, sufficient sulfamic acid to act as a halogen acceptor, water-soluble carbonate or bicarbonate, and sufficient excess sulfamic acid to react in water with carbonate / bicarbonate to produce carbon dioxide and the foaming required. A preparation according to claim 1, characterized in that it contains: 0.01 to 5 parts by weight of water-soluble inorganic halide; 25 to 60 parts by weight of a strong oxidizing agent which reacts with halide in aqueous solution to form hypohalite ions; 5 to 25 parts by weight of water-soluble carbonate or bicarbonate; 10 to 20 parts by weight of sulfamic acid; and the binder; and the pH is 1% by weight of the aqueous solution of the preparation between 1.0 and 5.0, preferably between 1.2 and 4.0. A preparation according to claim 1 or claim 2, characterized in that the inorganic halide sodium chloride is present in amounts of from 0.1 to 5 parts by weight. Preparation according to any one of the preceding claims, characterized in that it also contains anhydrous alkali metal phosphate (preferably from 10 to 30 parts by weight), non-reducing organic acid (preferably up to 20 parts by weight) and anhydrous surfactant (preferably up to 20 parts by weight) parts). 5. An effervescent biocidal product as previously described in Example 1, characterized in that it can be tabletable.