AU639481B2 - Microbicidal agent - Google Patents

Description

63 9 4SF R: 142631 FORM COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952 COMPLETE SPECIFICATION

(ORIGINAL)

FOR OFFICE USE: Class Int Class Complete Specification Lodged: Accepted: Published: Priority: Related Art: r.

aJ a Name and Address of Applicant: Address for Service: Butris Danha Iwassi 6 Burr Close Bossley Park New South Wales 2176

AUSTRALIA

Spruson Ferguson, Patent Attorneys Level 33 St Martins Tower, 31 Market Street Sydney, New South Wales, 2000, Australia i Complete Specification for the invention entitled: Microbicidal Agent The following statement is a full description of this invention, including the best method of performing it known to me/us S 017329 180990 5845/3 -1- TECHNICAL FIELD This invention relates to an acidic composition for killing microorganisms and methods of killing microorganisms.

BACKGROUND ART The struggle with pathogens has been a long and an awkward one.

Whereas medical science succeeded in finding a cure for most of them yet a small group, mainly viral, represented by AIDS; viral hepatitis B; and genital herpes are still a big challenge to medicine. The first two being a well recognized risk in blood transfusions as well.

Parasitic diseases such as hydatid disease, schistosomiasis and malaria are other diseases where an effective cure is still a long way off.

The real problem is to prepare a substance which, after administration into the body, kills the pathogen but leaves the tissues V intact perhaps with a limited degree of side effects, One choice is to .1.5 select a few substances which are killers of the pathogen but because of their chemical composition are destructive to living tissues too, then by mixing and passing them through different chemical and physical processes an end product Is produced which retains its effect on the pathogen but loses It on living tissues. It could be assumed that If a substance is that toxic and destructive to cells in vitro, then little could be done in the direction of changing its properties to the degree of losing Its effect on living tissues but one possibility should not be ignored, that is by mixing and passing them through the above mentioned processes this will lead to the breakdown of the original structure, which determines its toxic 5 effect on tissues, and the formation of a new one, otherwise if the substance maintains its original structure it is doubtful it wouldn't destroy normal tissues. It is also possible that the original structure could remain the same in the mixture but by the effect of dilution, this purpose could be achieved.

Furthermore, there is an advantage in favour of the body namely the compensatory mechanisms of various systems to detoxicate and excrete a given amount of any substance; which would be the end product in this case; up to a certain degree over a unit period of time, a feature which doesn't exist in viruses and other pathogens because of their one-unit structure.

The time interval necessary for getting the optimal effect of the end product, which could be handled by the body but not by the pathogens will TCW/877v -2 determine the end result in terms of success or failure of the treatment.

No matter what sort of changes occurred to the end product, there must be some original effect of the basic substances left over in one form or another since it is impossible to get completely inert substances out of a toxic one in terms of dilutive effect. It is this leftover effect that is going to destroy the pathogens.

OBJECTS OF INVENTION It is an object of this invention to provide an acidic composition for killing microorganisms.

I

*S

'15 Another object is killing microorganisms.

Another object is humoral disturbances in Another object is host.

to provide an acidic pharmaceutical composition for to provide a host.

to provide a method of treating cellular and a method of killing microorganisms in a 5:

S.

S

S

*5* Another object body fluid.

'Another object Another object substance.

is to provide a method of killing microorganisms in a to provide to provide method method of treating fungi at a locus.

of killing microorganisms in a Another object is substrate.

to provide a method of killing microorganisms on a nT rI fS I IR F OF TNVFNTTnN As used throughout the specification and claims the term, host, refers to any living cell that is not a patogen. It also refers to cUlTUn s o" ce(s re cultures of cells. Typically these 4 cl s r fc d in mammals, fish or plants.

The term, pathogen, is used throughout the specification and claims to mean any orgatiism capable of causing a diseased state.

The present inventor has surprisingly found that when glacial acetic acid and absolute ethanol are combined and then diluted, this combination has antimicrobial activity.

According to a first embodiment of this invention there is provided an acidic composition for killing microorganisms comprising a carboxylate compound of the formula: TCW/'877v tt 4 V f.«

R

1

CH

2

COOH

where RI is CH 3

(CH

2 )0-1 5 alkyl, H, or

(CH

3 2

CHCH

2 or a salt or acid salt thereof; or an inorganic acid; together with an alcohol of the formula:

R

2

CH

2

CH

2

OR

3 where R 2 is C 1

-C

16 alkyl, H, R(OCH 2

CH

2 )q.1, or

R

3 is H; R is C 1

-C

20 alkyl; and q is 2 to 10; or an alcohol selected from the group consisting of benzyl alcohol, chlorbutol, chlorocreosol, creosol phenethyl alcohol and phenol, with the provisos that said composition does not further include a biocide topically effective in killing acne bacteria, and when the alcohol is ethanol it is absolute ethanol.

.9 According to a second embodiment of this invention, there is provided a composition, hereinafter designated P2, comprising: 0.5 volumes of Pl; and volumes of normal saline; wherein P1 is the composition of the first embodiment having the following components in the following ratio ranges: about 20 to about 80% by volume normal saline; about 10 to about 60% by volume absolute ethanol; and about 5 to about 15% by volume glacial acetic acid.

According to a third embodiment of this invention, there is provided an acidic pharmaceutical composition for killing microorganisms comprising: a carboxylate compound of the formula: 30 RICH 2

COOH

where R 1 is CH 3

(CH

2 )o- 15 alkyl, H, or

(CH

3 2

CHCH

2

Q

or a salt or acid salt thereof; or an inorganic acid; together with IPrlv21\0033iTCW an alcohol of the formula:

R

2

CH

2

CHO

2

R

3 where R 2 is C 1

-C

16 alkyl, H, R(OCH 2

CH

2 )q.1, or R3 is H; R is C 1

-C

20 alkyl; q is 2 to 10; or an alcohol selected from the group consisting of benzyl alcohol, chlorbutol, chlorocreosol, creosol phenethyl alcohol and phenol, with the proviso that said pharmaceutical composition does not further include a biocide topically effective in killing acne bacteria; and a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant.

The acidic pharmaceutical composition can further include a polyhydric alcohol of the formula: cH2-(CH2)P-(C i H)n m H2 T O O R4 R 5

R

6 where m 1-15, p 0-15, *o

R

4 is stearic acid, palmitic acid, oleic acid, nitro or H

R

5 is stearic acid, palmitic acid, oleic acid, nitro or H .0 20 R 6 is a choline ester of phosphoric acid, nitro, H, sodium phosphate or potassium phosphate.

Further embodiments of the invention include processes for preparing the acidic S: composition and the acidic pharmaceutical composition, Generally the carboxylate compound is selected from 4-(2methylpropyl)benzeneacetic acid, stearic acid, acetic acid or glacial acetic acid and the salts and/or acids thereof and other like carboxylate compounds or mixtures thereof.

Generally the inorganic acid is selected from sulphuric acid, nitric acid, phosphoric acid, hydrochloric acid, sulphurous acid, nitrous acid, bromic acid, iodic acid or other like inorganic acids and mixtures thereof. Preferably glacial acetic acid is used.

30 The acidic pH can range from pH 1 to pH 7. The amount of carboxylate compound can vary from 0.5% to 1.5% based on the total final composition. Typically 1% based on total volume of the final composition is used.

0 Generally the alcohol can be selected from hexanol, phenethyl alcohol, i polyoxyethylene alcohols, propyl alcohol, stearyl alcohol, myristyl alcohol, ethanol or other like alcohols and mixtures thereof. Typically ethanol is used, preferably absolute ethanol.

IPrlv2\0003TCW\GSA The amount of alcohol can vary from 1% to 6% based on the total volume of the final composition. Typically 3% based on the total volume of the final composition is used.

The polyhydric alcohol can be selected from glycerol, lecithin, nitroglycerin, potassium glycerophosphate, sodium glycerophosphate or other like polyhydric alcohols and mixtures thereof. Typically glycerol is used.

Other compounds can be used which act in a similar way to the polyhydric alcohol. These are typically sucrose, propylene glycol, polyethylene glycol, fixed vegetable oils, such as arachis, sesame, cottonseed and maize oil, ethyl oleate, fatty acids, cellulose, dextran sulphate sodium or other like compounds.

The amount of polyhydric alcohol can vary from 0% to 8% based on the total volume of the final composition. Typically 0% based on the total volume of the final composition is used. Alternatively, typically 6% based .1 5 on the total final pharmaceutical composition is used.

SThe diluent and/or carrier can be selected from normal saline, Ringers solution, dextrose, mannitol, normal serum albumin, plasma substitutes (such as haemacel), sodium bicarbonate, calcium gluconate, sterile water, isotonic sodium chloride, lactose, sorbitol, mannitol, fructose, starches, calcium phosphate, calcium carbonate, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, syrup, methyl cellulose, methyl- and propyl-hydroxybenzoates, talc, magnesium stearate, mineral oil, propylene gl,col, liquid polyethylene glycol, vegetable oils and suitable mixtures thereof. Typically normal saline is used.

The adjuvant can be selected from Freund's complete or incomplete adjuvant, Adjuvant 65 (containing peanut oil, mannide monooleate and aluminium monostearate), mineral gels such as aluminium hydroxide, aluminium phosphate and alum, surfactants such as hexadecylamine, 3 octadecylamine, lysolecithin, dimethyldiottadecylammonium bromide, N', N'-bis(2-hydroxyethyl)propanediamlne, methoxyhexadecylglycerol and pluronic polyols, polyanions such as pyran, dextran sulphate, polyIC, polyacryllc acid and carbopol, peptldes and amino acids such as muramyl dipeptide, dimethylglycine, tuftsin, oil emulsions and mixtures thereof, The excipient can be selected from inert diluents such as sodium carbonate or sodium phosphate, or from granulating and disintegrating agents such as corn starch, or alginic acid, or from binding agents such as TC1/877V -6 gelatin or acacia, or from lubricating agents such as stearic acid, or from suspending agents such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate or polyvinylpyrrol done, or from dispersing or wetting agents such as polyoxyethylene stearate, heptadecaethyleneoxycetanol, polyoxyethylene sorbitol monooleate or polyoxyethylene sorbitan monooleate and mixtures thereof.

The amount of diluent and/or carrier can vary from 81% to 98.5% based on the total volume of the final composition, Typically 96% based on the total volume of the final composition is used. Alternatively, typically 90% based on the total volume of the final pharmaceutical composition is used.

-Ge. ea 4y The components of the composition, designated P1, are in the following ratio ranges; about 20 toA80% by volume normal saline; about 10 tob% by volume absolute ethanol; and about 5 to by volume glacial acetic acid.

Typically the ratio is 6 volumes normal saline; 3 volumes absolute ethanol; j and 1 volume glacial acetic acid.

Generally the components of the pharmaceutical composition, designated PIG, are in the following ratio ranges: about about 20 to 80% by volume glycerol; about 10 to, by volume absolute ethanol; and about 5 too, 5% by volume glacial acetic acid.

Typically the ratio is 6 volumes glycerol; 3 volumes absolute ethanol; and 1 volume glacial acetic acid.

According to a fourth embodiment of this invention there is provided a pharmaceutical composition, hereinafter designated P2G, comprising volumes of PIG as defined in the second embodiment and 5 volumes of normal saline.

According to a fifth embodiment of this invention there is provided a method of treating cellular and humoral disturbances in a host requiring such treatment comprising administering to said host an effective amount of the acidic composition of the first or second embodiment or the acidic pharmaceutical composition of the third or fourth embodiment.

According to a sixth embodiment of this invention there is provided a method of killing microorganisms in a host, comprising administering an effective amount of the acidic composition of the first or second Ch. 877v y1 -7embodiment or the acidic pharmaceutical composition of the third or fourth embodiment.

According to a seventh embodiment of this invention, there is provided a method of killing microorganisms in a body fluid, comprising adding to said body fluid an effective amount of the acidic composition of the first or second embodiment or the acidic pharmaceutical composition of the third or fourth embodiment.

According to an eighth embodiment of this invention, there is provided a method of treating fungi at a locus, comprising applying to said fungi at a locus a fungicidally effective amount of the acidic composition of the first or second embodiment or the acidic pharmaceutical composition of the third or fourth embodiment.

According to a ninth embodiment of this invention, there is provided a method of killing microorganisms in a substance comprising mixing the substance with an effective amount of the acidic composition of the first or second embodiment or the acidic pharmaceutical composition of the third or fourth embodiment.

Typically the substance is a liquid, lotion, powder, cream, gel, syrup, emulsion, ointment, injection, lozenge, liniment, paint, paste or pastille.

According to a tenth embodiment of this invention, there is provided an acidic pharmaceutical composition for killing microorganisms comprising: a carboxylate compound of the formula:

R

1

CH

2

COOH

or a salt or acid salt thereof; or an inorganic acid; together with an alcohol of the formula: RCH2CH2OR3 2 where R 2 is C1-C16 alkyl, H, R(OCH2CH2)qor R3 is H; 0 R is C-C20 alkyl; and q is 2 to 10; or an alcohol selected from the group consisting of benzyl alcohol, chlorbutol, chlorocreosol, creosol phonethyl alcohol and phenol; '[P2 o CW 7a with the provisos that when the alcohol is ethanol it is absolute ethanol and the composition does not include a quick breaking foam agent, except when said quick breaking foam agent is an aliphatic alcohol of the formula R 2

CH

2

CH

2 0R 3 According to an eleventh embodiment of this invention, there is provided an acidic pharmaceutical composition for killing microorganisms comprising: a carboxylate compound of the formula:

R

1

CH

2

COOH

where R 1 is CH 3

(CH

2 )o- 15 alkyl, H, or

(CH

3 2

CHCH

2 or a salt or acid salt thereof; or an inorganic acid; together with an alcohol of the formula:

R

2

CH

2

CH

2

OR

3 where R 2 is C 1

-C

16 alkyl, H, R(OCH 2

CH

2 )q- 1 or 0

R

3 is H; R is C-C 20 alkyl; and *q is 2 to 10; or 20 an alcohol selected from the group consisting of benzyl alcohol, chlorbutol, a chlorocreosol, creosol phenethyl alcohol and phenol; with the provisos that the composition is not for topical application and when the alcohol is ethanol it is absolute ethanol.

According to a twelfth embodiment of this invention, there is provided an acidic pharmaceutical composition for killing microorganisms comprising: a carboxylate compound of the formula:

R

1

CH

2

COOH

where R 1 is CH 3

(CH

2 0 1 5 alkyl, H, or

(CH

3 2

CHC

S 30 or a salt or acid salt thereof; or an inorganic acid; together with (ii)(a)an alcohol of the formula:

R

2

CH

2

CH

2

OR

3 IPrv2)\0003oo j):TCW\SA -7bwhere R 2 is C 1

-C

16 alkyl, H, R(OCH 2

CH

2 )q.

1 or

R

3 is H; R is C 1

-C

20 alkyl; q is 2 to 10; or an alcohol selected from the group consisting of benzyl alcohol, chlorbutol, chlorocreosol, creosol phenethyl alcohol and phenol; and a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant with the proviso that the composition does not include a quick breaking foam agent, except when said quick breaking foam agent is an aliphatic alcohol of the formula R 2

CH

2

CH

2 0R 3 According to a thirteenth embodiment of this invention, there is provided an acidic pharmaceutical composition for killing microorganisms comprising: a carboxylate compound of the formula:

R

1

CH

2

COOH

where R I is CH 3

(C

2 0 15 alkyl, H, or

(CH

3 2

CHCH

2

I,

or a salt or acid salt thereof; or an inorganic acid; together with 20 an alcohol of the formula:

R

2

CH

2

CH

2

OR

3 where R 2 is C 1

-C

16 alkyl, H, R(OCH 2

CH

2 )q.i,

S

*SSS

S

OS S

S

S S or R3 is H; R is CI-C 20 alkyl; q is2 to 10; or an alcohol selected from the group consisting of benzyl alcohol, chlorbutol, chlorocreosol, creosol phenethyl alcohol and phenol; and a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant with the proviso 30 that the composition is not for topical application.

According to a fourteenth embodiment of this invention, there is provided a pharmaceutical composition, hereinafter designated P2, comprising: f k IPlllvi\OOT3:tCi AOSA 6> 7cvolumes of P1, and volumes of normal saline.

According to a fifteenth embodiment of this invention, there is provided a pharmaceutical composition, hereinafter designated P2G, comprising: 0.5 volumes of P1G of the twelfth or thirteenth embodiment, and volumes of normal saline.

According to a sixteenth embodiment of this invention, there is provided a method of killing microorganisms in a host, comprising administering to said host an effective amount of the acidic pharmaceutical composition of the tenth, eleventh, twelfth, thirteenth, fourteenth or fifteenth embodiment.

According to a seventeenth embodiment of this invention, there is provided a method of killing microorganisms in a body fluid, comprising adding to said body fluid an effective amount of the acidic pharmaceutical composition of the tenth, eleventh, twelfth, thirteenth, fourteenth or fifteenth embodiment.

According to an eighteenth embodiment of this invention, there is provided a method of treating fungi at a locus, comprising applying to said fungi at a locus a fungicidally effective amount of the acidic pharmaceutical composition of the tenth, eleventh, twelfth, thirteenth, fourteenth or fifteenth embodiment.

According to a nineteenth embodiment of this invention, there is provided a method 0*@ do&: 20 of killing microorganisms in a substance comprising mixing the substance with an effective amount of the acidic pharmaceutical composition of the tenth, eleventh, twelfth, thirteenth, fourteenth or fifteenth embodiment.

According to a twentieth embodiment of this invention, there is provided a method of killing microorganisms on a substrate comprising applying to the surface of the substrate an effective amount of the acidic composition of the first or second embodiment or the acidic pharmaceutical composition of the third or fourth embodiment.

The substrate may be a solid, a host's skin (including human skin) or tissue (including human tissue), The composition and/or pharmaceutical composition can be administered by various 30 routes such as oral, rectal, transdermal, subcutaneous, intravenous or intramuscular, Typically the composition and/or pharmaceutical composition is injected into the host, Generally the effective amount for intravenous injection is 1ml, 12 hourly for 7 days and intramuscular injection is 3ml, 12 hourly for a total of The microorganisms susceptible to the composition and/or pharmaceutical composition can be selected from bacteria, fungi, protozoa, viruses or parasites, P* ;vl\QolQ TCW -8 BRIEF DESCRIPTION.OF THE DRAWINGS Fig. 1. LPM. MIF is active only in free form.

Fig, 2. Loss of the solid structure of MIF crAused by predisposing factors.

Fig, 3. Ionizing radiation invariably prodjces malignant transformation which explaint the structural chailge in MUF enabling the causative agent to dictate the LPM, Fig. 4. LPM repr,;;ents a complex protein factor of high molecular weight which exerts its action on nuclear DNA. it is formed by components from cytoplasmic RNA and HTGCS-RNA virus. The viral corrponent should not be confused with the concept of "toxin", it is a factor with the- same biological properties as the virus.

0900

S

me..

00 SO 0 0 '.0 00 0 S S *5 6 0050 p 5

IS..

CS..

06

S

~0* 0* ~S 0 BASIS OF THE INVENTION When fruit juices are allowed to spoil naturally alcoholic fermentatiob by yeasts usually takes place first, If these products are exposed to tho air an acetic acid fermentation is mnost likely to follow caused by bacterial growth (Acetobacter) whch ox' .Iize elCohol to acetic acid obtaining onergy for their life process5es, This succession of fermenrtation is used in, t M'anacture of vinegar which is primarily a solutlon of acetic acid together with vorious flavouring substances.

yeast 061126- 2 C 2 11 5 0H glucose ethyl alcohol Z 002 energy Ace tobacte r C 1 H OH 02 CH COOI H energy 002 alcothol acetic &cid 0 04 a 2( components are 01l part of~ the tormal body metabolic processes.

0 G(Ykcerol aftd acetic acW are well known com~pounds to integrate well with bod~y tissues (physiolokycal chemistry! metabolism of llpid.O. Furthermore, glycerol forms the vehicle (excipient) of allergy vaccine drops (oral) in current use, and acetic acid has been u ,euo in the f rn of ophthalmic drops in, the treatment of one form of spring catarrh (caused by Morax Axenfeld bacilli) in. much higher concentrations than in P2G.

It can be easily concluded that this effect Is not due to art enzymatic.

inhibition or an interfe:',ence with a sequence of' chemical reactis but by TCWJ877V 9 direct destrucLion of the "building blocks" of the microbes (cell membrane; cytoplasm) mainly by acetic acid which gives the impression that it could impose the sam, effect on a wide range of microbes.

Long term side effects are most unlikely because of the compatibility of the components with normal tissues. The only point to consider Is the formation of "ester" as a result of the reaction between alcohol and the acid which in this case is ethyl acetate. The latter will only be formed in small amounts which could be easily detoxified and eliminated from the body In a short time, This all means that P2G is a safe compound.

P2G is a compound capable of destroying viruses, the most famous exaiple of a virus is AIDS virus. There is enough scieittific reasons to believe that it should have the same effect in other viral diseases 'ike serum hepatitis; genital herpes and serious tropical and non-tropical viral 5 infections, It could also provide an important clue as to the controversial role of viruses in triggering some types of tumours, whether benign or malignant. This role is in contrast to the well established one Sof the RNA ieukoviruses in animal oncology. There is a very high posslh!lity of being just ar valuable in the treatment of leprosy, tuberculosis and chronic osteomyelitis. In general, it should be tried in every microbial disease resistant to all sorts of antimicrobial therapy.

P2Q is an important means to verify the validity of different theories concerning "aetiology" in diseases suspected to be incited by an infectious agent (microbe) as an initiating factor. This In turn means that all latter stages of the disease could be prevented by intervening at an early stage, A very good example fitting in this context is rheumatoid disease and other allied connective tissue disorders. However the latter are only one group of diseases all characterized by unknown aetiology; variable contributing factors; disturbed immune mechanisms and autoimmunity; and genetic predisposition besides the fact that some of them are associated and evolve to a disease belonging to another group. There are many examples some of them are the association of ulcerative colit s with ankylosing spondylltis and the later evolution to carcinoma of the colon; specific skin lesions asso. ted with many different diseases like erythema nodosum; the association between bronchial asthma and eczema. One more example Is the disturbance or imbalance between subsets of lymphocytes in 10 sarcoldosis, AIDS, systemic lupus erythematosus and atopic dermatitis. All these diseases are incurable.

It is absolutely essential to study the response of different diseases of the above mentioned groups to empirical treatment with P2G which could provide an invaluable information as to the nature of this association.

Examples from each group of diseases could be selected for this purpose as follows: 1. Malignancies:- Viruses cause cell instability and are therefore implicated.

Blood: a) Leukaemias (acute and chronic): spontaneous and post-irradiation varieties. There is a possibility of high fever during the course of treatment in the acute type.

Lymphomas: e.g. Burkitt's lymphoma, Carcinomas of: Lung, Larynx, Oesophagus, Stomach, Colon, Livwr, Breast, Ovary, Uterine Cervix, Adrenal Gland and Urinary Bladder.

Bone Tumours.

C" 2. Connective tissue disorders:- Rheumatoid disease; Ankylosing spondylitis; Systemic lupus erythematosus; Polymyositis and dermatomyositls.

3. Isolated diseases of altered immune response:- Ulcerative colitis; Crohn's disease; severe cases of bronchial asthma, 4. Skin Diseases:- Atopic eczema; Psoriasis; Alopecia; Exfoliative dermatitis; 11 46 Erythema multiforme; Vltilgo.

Vitiligo is associated In a significant number of cases with autoimmune endocrine disorders like Addison's dlsease, hyperthyroldlsm and pernicious anaemia. In pernicious anaemia there is statistically significant increase in deaths from gastric carcinoma while in polycythemia vera there is inevitable progresson to a refractory state with anaemia, myelofibrosis or acute leukaemia.

Blood Diseases: Addisonian pernicious anaemia; Sickle-cell anaemia; TCW/877v 11 Haemophilla and von Willebrand's disease.

6. Sarcoidosis: In this condition there is an element of disturbed immune mechanism; multisystem involvement; specific skin lesion which occurs in other conditions i.e. Erythema Nodosum. In systemic sarcoldosis the histological picture is similar to that of tuburcle follicles, where as in individual organs the same histological features take place in lymph nodes draining organs affected by carcinoma, e.g. carcinoma of the stomach.

7. Cystic Fibrosis All the above examples confirm the fact that the basic disorder is biochemical brought about by an unknown causative agent leading to cellular T: and humoral disturbance aided later on by structural damage.

Once the treatment with P2G starts all other forms of treatment should 4 be stopped and only resumed temporarily to achieve biochemical and clinical control until the treatment with P2G is over which only takes one week.

Polymyositis and dermatomyonitis is thought to be caused by viral Infection (overt or latent), the virus has never been identified or grown in tissue cultures neither this disease is infectious, unlike other viral diseases, e.g. Influenza.

The concept of a virus in malignant and other diseases suspected to be caused by viruses is a modified one, Malignancy is simply continuous and uncontrol'(ed mitosis, The latter starts after the fertilization of ovum by a sperm and reaches its physiological limit during different stages of development (fetal, neonatal, childhood and adult life) until all the organs are fully developed in structure and physiologically mature, after which it stops and only restarts in variable degrees of differentation in response to injury or physiological replacement especially so in less specialised tissues like skin ans the lining of the gastrointestinal tract, The control mechanism is lost In malignant diseases suggesting the existence of mitosis inhibiting factor (MIF) which lost its control fun-tion, this Is achieved by inactivation of this factor which is in active form once the physiological limit is reached. Whatever the causative agent Is it must be tissue specific and related to a specific genetic code (template and sequence of amino acids), Thiis s he reason why leukaemia and other malignant diseases can't be transferred from one patient to another by transplanting malignant growths neither it can be TCR/877v i2 done between man and animal explaining the difficulty of growing cancer cells in tissue cultures and confirming the nec i:,ity of the homeostatic influence of the body in general for the process to manifest itself.

The process of inactivating MIF is achieved by lock up mechanism (LPM) which is explained in a simplified way in Fig. 1, this phenomenon explains the primitive nature of malignant cells with big nuclei -iany in the process of mitosis.

Ionizing radiation and some chemicals (carcinogens) always result in an inevitable malignant transformation which indicates that LPM doesn't take place by an accidental match up or interlock between the causative agent and MIF, this is most unlikely between two elements with high degree of complexity and specificity. It is highly possible that ionizing radiation and other predisposing factors bring about some sort of changes in the structural nature of MIF in a way that the causative agent always dictates the LPM causing its inactivation but regaining its physilogical function once the causative agent is removed and MIF is in its free and active form (Fig. 2 3).

As a matter of fact LPM shown in Fig. 1 has no place in the pathogenesis of malignant diseases, otherwise cancer would've been a group of rare diseases due to the extreme difficulty for an accidental LPM to take place due to the complexity of the two elements. It is always the mechanism shown in Fig. 2 which lies behind the pathogenesis of cancer.

The causative agent in spontaneous leukaemia is of much more biochemical impact on MIF than that caused by leukaemia secondary to ionizing radiation, in the first case the biochemical factors triggering malignant transformation are released by the causative agent itself while in the second case it is the predisposing factor that mediates these biochemical changes making MIF ready to be inactivated by a biologically less active similar agent, the latter is always an important part of the process.

r''SO In blood malignant di eases LPM could occur at any stage of cellular maturation giving rise to the type and degree of differentiation of that particular malignant condition depending on the causative agent and its specific biochemical impact.

The first step in malignant transformation is biochemical, The latter takes years to manifest itself clinically as a smaHl mass or nodule discovered by clinical or radiological examination, in some cases this could take up to fifteen years. During this period of time MIF; already in TCH/877v

L

ri 13 the process of transformation; still exerts Its physiological function indicated by the rapid progession of cell division after the clinical diagnosis is made with the spread of malignant cells within a relatively short period of time suggesting that LPM is only recent and final event and confi-"ing the functional stability of MIF compared to the structural one which is an extremely crucial point signifying that malignant diseases resulting from Ionizing radiation and other predisposing factors are curable just like the spontaneous types once the causative agent is destroyed and MIF released in its free form to exert it physiological function.

There seems to be some factors which determine the site of the organ to be affected by LPM since the malignant growth starts in one localized area at a time the whole organ is under the same homeostatic impact regarding MIF for that particular type of cells.

*8 15 In diseases characterized by altered immune response and disturbance of regulatory immune mechanisms the LPM involves biochemical factors controlling cellular and eventually humoral elements leading to structural damage and multisystem involvement, whereas in autoimmune diseases this could also include the inactivation of self-recognition factor (SRF) as opposed to non-self varieties (stimulated by different external antigens) leading to the devastating consequences of autoimmune diseases. The 41. d process of antibody formation in response to external antigenic stimuli is S guided by SRF.

All the above mentioned conditions are caused by human type, genetic 6. 25 code specific, non-infectious RNA viruses (HTGCS-RNA virus) producing biochemical factors composed of high molecular weight protein. These viruses are of unknown biological properties up until now.

In every disease there Is a primary pathological process characterized *e by the essential signs and symptoms, not all of the latter manifest kt $3 themselves clinically, and in different patients their number is variable for the same disease in addition to the non-specific ones which are shared by other totally different diseases.

Sometimes the patient presents with only one symptom or sign and together with equivocal and inconclusive investigations lead to enormous difficulties in diagnosis. This indicates that there is a variable range of secondary effects brought about by the release of some biochemical factors from the site of the fully developed primary pathological process TCN/877V 14 leading to other clinical features the development of which depends on the genetic predisposition of the patient in regard to the interaction between the causative agent and the affected tissue.

In malignant diseases the basic process is multiplication of cells leading to the invasion and destruction of other tissues. Cancer cells compete with normal tissues for nutrients and bring in a process of indefinite proliferation, their number soon demands all the nutrition available to the body causing weight loss but there are other secondary pathological processes, for example bronchial carcinoma causing manifestations of endocrine; neurological and other disorders marked as non-metastatic extrapulmonary manifestations. Lymph nodes draining some carcinomas undergo histological changes of sarcoidosis similar to those c, caused by some fungal infections and at the same time it is the same histological picture of systemic sarcoidosis which is again similar to those caused by pulmonary tuberculosis and the exposure to beryllium which a is a rare event. In the idiopathic type, systemic variety sarcoidosis Is the primary process whereas in beryllium exposure it is a secondary event caused by the release of biochemical factors similar to those in the idiopathic type. Clinically the latter is basically quite similar to connective tissue disorders (multisystem involvement) while serologically it gives the impression of being totally unrelated, It is the idiopathic type which is caused by HTGCS-RNA virus of biological properties different from those in other diseases.

Erythema Nodosum is a specific skin lesion but it isn't a disease by itself. It is caused by bacterial, fungal and viral diseases. It seems that all these different diseases produce the same biochemical factor(s) as a secondary effect to the primary pathological process causing the same lesion, Pruritus is a non-specific symptom which is caused by different systemic diseases all producing the same biochemical factor(s) since the sensory nerve endings are stimulated by the same specific mechanism generating this type of response compared to other modalities of sensation like pressure, pain and temperature. Drugs also cause the above mentioned two conditions.

In connective tissue diseases the primary pathological disorder is that of joints, muscles and tendons but all share the multi system involvement to a variable degree and extent as a secondary consequence.

Almost all DNA Is located in the nucleus of the cell yet most of the TCW/877v 15 functions of the cell are carried out in the cytoplasm. This is achieved through the intermediary of another type of nucleic acid "RNA" the formation of which is controlled by DNA of the nucleus, the process being called transcription. The RNA Is then transported into the cytoplasmic cavity where It controls protein synthesis. The three types of RNA important in protein synthesis are mRNA, tRNA and rRNA.

The current theories state that DNA is the control centre of the cell in terms of chemical reactions and cell reproduction, the first being done by the formation of protein enzymes of the cytoplasm and In this way controlling cytoplasm activity, Whereas this concept explains the physiological sequence of events Swhich controls cell function the overall study of pathological conditions contradicts the validity of these theories.

.e The real situation is that DNA contains all the genetic codes and intrlnsic factors that keep the information of the genetic material and transfer it to the newly formed cells through the process of mitosis while cytoplasmic activities are under the control of cytoplasmic RNA through the release of protein enzymes and other biochemical factors which are genetically related to the DNA exerting, a process of interacting balance.

All DNA is located in the nucleus well protected and preserved since it represents the immortal extension of life for all species. Its main function is cell division and the transfer of the genetic information to the newly formed cells, the 'latter means structure and biochemical activities.

Integration or Incorporation of viruses in nuclear DNA means disturbance of the whole constitution (the genetic code) and deviation of the genetic information from Its normal pattern to be transferred later on a otenwy*rdsmai n e eli helte aeete h 0* t h el fre oai adsxcls i h atrcaeete h process of fertilization doesn't take place due to chromosomal aberrations or the fetus will not reach full term due to severe chromosomal anomalies.

Viruses act in the region of biochemical balance as shown In Fig. 4.

All the throe Oements i~e. DNA, RNA and the virus interact -through biochemical ft\ctors related to the genetic code. The whole cell is under the univers;O homeostatic influence of the body and DNA Is also affected by the cytoplasmic homeostatic control imposed by RNA.

As shown in the diagram it is more likely that the biochemical factors released by the virus are the ones which bring about LPM shown in Fig. 2 TCWI877v p. 16 rather than the virus itself. Whatever the mechanism is, destroying the virus will eliminate the whole process. The transformation in the structure of MIF is not disturbance of the pattern (It keeps the template and sequence of amino acids) but only becomes resilient (softer) losing its solid texture allowing the phenomenon of LPM to take place.

The nature of the biochemical impact on nuclear DNA could extend to include other processes like congenital defects similar to the mechanism by which rubella infection during pregnancy leads to congenital defects in the eye, ear and heart of the fetus, or chromosomal abnormalities like Philadelphia chromosome in chronic myeloid leukaemia.

The concept of viruses affecting the DNA of one type of cells transferred later on to the offspring leading to the same disorder is irrelevant because not all of the offsprings suffer from the same condition, and all types of cells which form the tissues and organs of the body later on in life come from one cell the fertilized ovum) which should b? intact regarding the genetic code and function, In benign tumours the involved viruses are biologically less active in terms of the released biochemical factors which are Inactivated by the immune system of the body causing the process of mitosis and the growth to stop, However the most important point is not the size of the tumour but the absence of metastases even If the tumour is large in size, in contrast to the malignant ones where metastasis has already occurred by the time of diagnosis even if it is small in size suggesting that Inactivation of MIF doesn't necessarily produce malignancy, the extension of the complicated process involves the production of cells by nuclear DNA with penetrating capability to spread locally and permeate through blood and lymph vessels leading to metastasis, this impact on nuclear DNA is imposed by the complex factor which is the result of LPM.

In premalignant conditions the interaction between two biologically active elemernts (RNA; HTGCS-RNA virus) leads to changes In the cytoplasmic biochemical factors producing the malignant transformation, This printciple Is easy to understand if one takes in consideration the mechanism behind the emergence of resistant strains of bacteria producing enzymes and Inactivating antibiotics previously sensitive to them, These changes are brought about by the alteration in the biological properties of the causative agent producing factors which transforms MIF to Its resilient TCN/877V f

I

17 texture leading to the fully developed malignant condition over a period of time which could be years.

This situation is similar to what happens in the spontaneous varieties which manifest themselves as malignant conditions from the start taking years to achieve the process of transformation when it first starts as a biochemical event, the involved agent being biologically more vigorous and active. Predisposing factors shortens 'hlis period drastically producing the transformation of MIF.

In ulcerative colitis it is the severe variety involving longer segments of the colon, more than ten years in duration which transforms to carcinoma of the colon indicating higher degree of infectivity (specific) and long duration of time consumed by the condition for malignant transformation. The latter doesn't happen in Crohn's disease which is caused by non-oncogenic type. These agents are of different groups and .5 strains which undergo mutation to more active strains producing S premalignant and eventually malignant transformation. For example the group causing connective tissue disorders are non-oncogenic and of different strains causing different diseases within the same group.

The blood malignant diseases the LPM involves any of the biochemical factors controlling each line of cells giving rise to the type of leukaemia, but at the same time and by the same mechanism LPM occur at any stage of maturation giving the full picture of type and differentiation of the malignant condition, However these factors belong to one group i,,e.

that controlling the cellular element of the blood, which means any shift in the zone of LPM due to the similarity between these factors leads to the transformation from one type to another. Chronic myeloid leukaemia after years of treatment transforms to acute myeloblastic type in many patients, and by the same mechanism polycythaemia vera transforms to acute leukaemia (shifting of LPM zone under the effect of the cytotoxic treatment). On the other hand this change could be done by the causative agent through the process of strain mutation justifying the concept some medical schools believe in stating the ankylosing spondylitis is a variant of rheumatoid disease (arthritis).

All the treatments for disorders caused by HTGCS-RNA viruses are non-specific (symptomatic) and incurable. In malignant diseases it involves the application of predisposing factors namely Ionizing radiation and cytotoxic drugs alkylating agents) to destroy the malignant cells TCW/877v

*C

18 which are less stable and more sensitive than normal ones to the effect of such measures, the virus being the least sensitive if at all. These measures are aimed at dealing with the end result of the disorders rather than the actual cause behind it. Long term remissions are achieved by periods of disconnection in the LPM mechanism. The same situation is encountered in bronchial asthma where after the damage is done producing bronchiolar constriction bronchodilaters are applied to reverse the process and in cases of severe attacks of status asthmaticus all attempts fail and death follows.

The marking of some chemical compounds in the blood and in association with malignant diseases are wrongly linked to aetiology at a time they are the result rather than the cause of the malignant process.

Diseases marked as of unknown aetiology or idiopathic and in many cases with genetic predisposition are highly suspicious and the response to .15 empirical treatment with P2G is absolutely essential even if the reason behind them is thought to be purely a biochemical one (non-microbial), s Examples include disorders of the C.N.S, like idiopathic epilepsy; Alzheimer's disease: muscular dystrophies and even psychotic depression.

Guillain-barre syndrome, multiple sclerosis and paralysis agitans (Parkinsonism) are already considered to be triggered by viral infection.

One more potential benefit of P2G is in parasitic diseases like hydatid disease, schistosomiasis, and malaria as examples. In hydatid disease the cyst can be injected with P2G to sterilize the contents prior to surgical removal followed later on by systemic treatment.

Some of the previously mentioned disorders don't end in permanent damage to the primarily affected system, e.g. bronchial asthma, while in the others the damage is Irreversible, e.g. rheumatoid disease destroying the articular surface of joints leading to permanent disability, This signifies the importance of early intervention before the damage starts, The role of HTGCS-RNA viruses in specific chromosomal Jisorders must not be underestimated especially so in the triosomies, e.g. Down's Syndrome which Is associated in a significant number of cases with visceral anomalies particularly congenital heart disease and acute leukaemia. P2G is a safe and non-teratogenic drug formed of components compatible with normal living tissues. This point is of crucial importance in verifying its benefits in chromosomal disorders affecting the fetus when there is a high degree of susceptibility (family background studies).

TCW/877v 19 DNA forms RNA which is located in the nucleolus transferred later on to the cytoplasm and eventually forming the ribosomes. It is In the latter where protein synthesis takes place clearly indicating to be the centre of control of cell function, while DNA keeps the genetic code and information serving the purpose of cell division and passing the genetic trait to the offsprings. When the life of the "organism" is over or is destroyed prematurely by external factors DNA has already escaped the damage through the process of reproduction and forms RNA to control the functions of the new "organism" repeating the same cycle.

BEST MODE AND OTHER MODE(S) FOR CARRYING OUT THE INVENTION A preferred acidic composition comprises: 1. Absolute ethanol 95% (C 2 HOH) mol. wt.46.07 3% 2. Glacial acetic acid (CH 3 COOH) mol. wt.60.05 1% 3, Isotonic (normal) saline 0.9% NaCI 96% A preferred process for preparing the acidic composition is the following: 1. Normal Saline (6 volumes) Absolute ethanol (3 volumes) Glacial acetic acid (1 volume) P1 (10 volumes).

2. Normal saline (5 volumes) P1 (0.5 volume) P2.

The final composition is P2 The composition is diluted at room temperature and mixed thoroughly after each step.

A bottle of the composition can be prepared as follows':- C *e Normal saline (90mls) P1 (9mls) P2 (99mls) Store below 30'C. Expiration date: None (acid and alcohol).

A preferred acidic pharmaceutical composition comprises four components: 1. Glycerol (CH20HCHOHCH 2 OH) mol. wt.92.09 6% 2. Absolute ethanol 95% (C 2

H

5 0H) mol. wt.46.07 3% 3. Glacial acetic acid (CH 3 COOH) mol. wt.60,05 1% 4. Isotonic (normal) saline 0.9% NaCl TCN/877v 20 A preferred process for preparing the acidic pharmaceutical composition is the following: 1. Glycerol (6 volumes) Absolute ethanol (3 volumes) Glacial acetic acid (1 volume) PIG (10 volumes).

2. Normal saline (5 volumes) PIG (0.5 volume) P2G.

The final pharmaceutical is P2G.

The pharmaceutical composition is diluted at rom temperature and mixed thoroughly after each step.

A bottle of the pharmaceutical can be prepared as follows: Normal saline (90mls) PIG (9mls) P2G <99mls) Store below 30 0 C. Expiration date: None (acid and alcohol).

oo 'w A preferred dosage for killing microorganisms in an adult human is the following: Dose: fIntravenous: 1 ml. iv. (12 hourly) for 7 days (one millilitre intravenously twice a day for seven days).

The intravenous therapy is highly recommended in clinical studies especially In adults.

3 mls. i~m. (12 hourly) for a total of 40 mls.

:(three millilitres intramuscularly twice a day for a total of forty millltitres).

Where the last dose is 1 ml.

The final pharmaceutical is suitable for children however the dosage must be altered as shown In the general formula below: Children: Clark's Rule weight of the child In -s X Adult dose.

150 TCW/B77v 21 Once the treatment with P2G starts all other forms of treatment should be stopped and only resumed temporarily to achieve blochemical and clinical control until the treatment with P2G is over which only takes one week.

The Invention is now described by way of the following examples.

EXAMPLE 1 The basic formula is: ACID ALCOHOL BASE OR CARRIER Normal Saline (6 volumes) Absolute Ethanol (3 volumes) Glacial Acetic Acid (1 volume) P1 Normal Saline (5 volumes) P1 (0.5 volume) P2 (See Footnote Below)* S. Different blood samples have been used by adding 0,2 volume of P2 to 1 volume of blood. Blood films, ESR and other Indices showed no significant changes. The same procedure was repeated by adding 0,2 volume of normal saline to 1 volume of blood as a control specimen which showed practically the same results. Below is a table of one of these blood samples of an adult male (42 years old) showing the original readings (before the addition of P2 and N. saline) compared to those after the addition of the above mentioned substances at 10, 30 and 60 minute intervals.

The numbers shown at the above equations are not final in terms of maximal concentration of the ingredients short of destroying blood.

s* TCW/877v 22 Minutes 30 Minutes 60 HMInutes

HAMATOLOGICAL

VJALUES

(COULTER

COUNTER)

Or Ig, nal Sample P2 N.

Saline P2 N Saline P 2' N Sali ne i WBC (x10 3 RBC (x10 6 Hg (g/dJ) Hct (W) MCV (Mm 3 M (Pg) MCHC (g/dl PLT (003) 9969 4 *a C *g '4I 6 4 41 8.0 5.15 15.6 .465 90.2 30.4 33.6 311 0 6,7 4.37 1340 .401 91,7 29.8 32. 5 261 6.4 4.33 12,8 .388 89.7 29,5 32.9 248, 6.6 4t.43 13.0 .402 90.6 29.3 323 259.

6,7 4.36 1248 .394 90.5 29,3 32.4 256.

6,7 4.51 13,1 .410 90.9 29.0 31 .9 255, 4.34 12.7 .393 90.6 29i 32.4 245.

Differential CQunt (Manual) Segs Eos Menc Lymphs 22 04 9 (Westergreeni) 15 51ood Film (Wri ght's F eain) 66 4 3 27 12

NAD

6, 9 NAD* NAD NAD No abnormality d1.tected TCH/877v .4 23 The drop in haematological values after the addition of P2 is mainly due to the effect of dilution since it forms 20% of the total volume.

EXAMPLE 2 Petri dish technique Lc-Ol) was used to test the effect of P2 "ABA: antibacterial activity" testing; medium: Oxoid sensitest; pH 7.4 temperature 370 C: incubation period 12 hours; inoculm: 106 organismli/ml, The follQwing results were obtained:- P2 saline base no antibacterial actvity P2 (50% glyercq' bate Imm bacteriaqfree zone P2 (100% glycerol base) 2mm bacteria-free zone The above results indicate the need for more suitable methods of testing for the antibacterial activity ?ince it is proved by th first result that the rapid diffusion of the aqueous base and its absorption by S. the agar medium prevented the exposure of E. cotL to the effect of P2. It 1" also indicates th 0 need for furtheY alterations in the nature of P2 base in the direction of making it of optimal molecular weight for optimal antibacterial activity, EXAMPLE 3 Another procedure was carried out using the same technique to study the effect of PZ components by adding the actual amount of each individual component to the same volume of glycerol (100%) Instead a- N, saline. Two plates were used, one with inoculum of 106 org/ml and another one with much lower concentration of g1j prepared ly taking a swab from the first one and culturing it into another' plate of the same specifications, 5 The following results were obtained- TCW/877v 24 Glycerol base (100%) 5 vol Pi eria-fiae_ ne (mm) IndividUal component and volume Inoculum Swab Culture I0 org/ml Glacial acetic acid (0.05) vol 1 1 Absolute ethanol (0,15) vol 6 0 Glacial acetic acid (0.05) vol Absolute ethanol vol 3 P2 rglycerol base vol ,J 1 2 Radius from "edge of well" S Two vhliles are used, The first is normal saline and the secortd I glycerol showing less anti-bacterial activity.

The above results consolidate the following points:- 1. The antibacterial effect of P2 is mainly due to the effect of acetic acid.

2. The combined effect of acetic acid and ethanol does not repres the sum of individual effects which indicates that there is some sort of synergism between the two compounds. This is confirmed by increased antibacterial activity when glycerol is used as a vehicle instead of St normal saline.

3. The effect of P2 shows that the reaction between acetic acid and 1 ethanol is enhanced when glycerol is used as a base instead of N.

saline. However it ias essential to include normal saline in the .experimental procedures sInce- it is a physiological solution which allows the study of P2 components effect on blood samples while glycerol containing the same concentration of P2 components allows to study their effect on bacteria, It could be assumed that the major products of P2 is not ethyl acetate expected to form as a result of the re&ction between acetic acid and ethanol due to the abrence of optimal experimental conditions lie. a TCH/877v

W"

1suitable reflux temperature of approximately 77*C; and a catalyst

(H

2 gS 4 and the presence of large volumes of water saline) which hinders the reaction. Furthermore, ethyl acetate is insoluble in water and it separates forming a top clear layer.

The microbial effect of acetic acid and absolute ethanul in combination and in a concentration that doesn't destroy normal tissues (blood sample) points to the importance of studying their effect on viruses; bacteria; and other microbes. This combination is considered biologically compatible with normal living tissues.

Extenive experimental work in animals (preferably rabbits) should be carrt d out first studying the effect on their normal offsprings. This could be done in conjunction with laboratory work in the field of tissue culture where mitosis and meiosis are studied under the influence of P2G analysing the effects on the karyotype, the latter provides information 15 about the number and configuration of the chromosomes.

Destructive substances could be dealt with in the direction of making them non-destructive to tissues but still destructive to microbes.

0 INDUSTRIAL APPLICABILITY Compositions made in accordance with the invention can be used for killing microorganisms. Compositions made in accordance with the invention can be used for treating fusgi at a locus. Compositons made in accordance w ith the invention can be used for treating cellular and humcral 0

S

oeooi l TCNH/877

Claims (24)

1. 26- The claims defining the invention are as follows: 1. An acidic composition for killing microorganisms comprising: a carboxylate compound of the formula: R 1 CH 2 COOH where R 1 is CH 3 (CH 2 0 o 15 alkyl, H, or (CH 3 2 CHCH 2 or a salt or acid salt thereof; or an inorganic acid; together with an alcohol of the formula: R 2 CH 2 CH 2 OR 3 where R 2 is C 1 -C 16 alkyl, H, R(OCH 2 CH 2 )q.i, or R 3 is H; 15 R is C 1 -C 20 alkyl; and q is 2 to 10; or an alcohol selected from the group consisting of benzyl alcohal, chlorbutol, chlorocreosol, creosol phenethyl alcohol and phenol, with the provisos that said composition does not further include a biocide topically effective in killing acne S 20 bacteria, and when the alcohol is ethanol it is absolute ethanol. 2. The composition of claim 1, wherein the carboxylate is selected from the group consisting of 4-(2-methylpropyl)benzeneacetic acid, stearic acid or acetic acid and salts or acids thereof and mixtures thereof. 3. The composition of claim 1 or 2, wherein the carboxylate is acetic acid. 25 4. The composition of claim 3, wherein the carboxylate is glacial acetic acid. The composition of claim 1, wherein the inorganic acid is selected from S sulphuric acid, ntitric acid, phosphorus acid, hydrochloric acid, nitrous acid, bromic acid, iodic acid or sulphurous arid. 6. The composition to any one of claims 1 to 5, wherein the alcohol is selected 30 from the group consisting of hexanol, phenethyl alcohol, polyoxyethylene alcohols, propyl alcohol, stearyl alcohol, myristyl alcohol, ethanol and mixtures thereof. 7. The composition of any one of claims 1 to 6, wherein the alcohol is hexanol, myristyl alcohol or absolute ethanol. IPrlv2 \0033:TCW 27 8. The composition of claim 7, wherein the alcohol is absolute ethanol or hexanol. 9. The compositon of any one of claims 2 to 10, wherein the components of the composition, hereinafter designated P1, are in the following ratio ranges: about 20 to about 80% by volume ncnral saline; about 10 to about 60% by volume absolute ethanol; and about 5 to about 15% by volume glacial acetic acid. The composition of claim 9, wherein the ratios are: 6 volumes normal saline; 3 volumes absolute ethanol; and 1 volume glacial acetic acid. 11. A composition, hereinafter designated P2, comprising: volumes of P1 as defined in claim 10 or 11 and 5 volumes of normal saline wherein P1 is the composition of any one of claims 1 to 10 having the following components n the following ratio ranges: about 20 to about 80% by volume normal saline; about 10 to about 60% by volume absolute ethanol; and about 5 to about 15% by volume glacial acetic acid. 20 12. An acidic pharmaceutical composition for killing microorganisms comprising: a carboxylate compound of the formula: RICH 2 COOH where R 1 is CH 3 (CH 2 )0- 1 5 alkyl, H, or (CH 3 2 CHCH 2 or a salt or acid salt thereof; or an inorganic acid; I: together with an alcohol of the formula: R 2 CH 2 CH 2 OR 3 30 where R 2 is CI-C 16 alkyl, H, R(OCH 2 CH22)q., or R 3 is H; R is CI-C 20 alkyl; q is 2 to 10; or SIPDrv2WOOa33lTCW ^*1 -28- an alcohol selected from the group consisting of benzyl alcohol, chlorbutol, chlorocreosol, creosol phenethyl alcohol and phenol, with the proviso that said pharmaceutical composition does not further include a biocide topically effective in killing acne bacteria; and a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant. 13. The pharmaceutical composition of claim 12, wherein the carboxylate is selected from the group consisting of 4-(2-methylpropyl)benzeneacetic acid, stearic acid or acetic acid and the salts and/or acids thereof and mixtures thereof. 14. The pharmaceutical composition of claim 12 or 13, wherein the carboxylate is acetic acid. The pharmaceutical composition of claim 14, wherein the carboxylate is glacial acetic acid. 16. The pharmaceutical composition of claim 12, wherein the inorganic acid is selected from sulphuric acid, nitric acid, phosphorus acid, hydrochloric acid, nitrous acid, chromic acid, perchloric acid, bromic acid, iodic acid or sulphurous acid. 17. The pharmaceutical composition of any one of claims 12 to 16, wherein the alcohol is selected from the group consisting of hexanol, phenethyl alcohol, polyoxyethylene alcohols, propyl alcohol, stearyl alcohol, myristyl alcohol, ethanol and mixtures thereof. 20 18, The pharmaceutical composition of any one of claims 12 to 17, wherein the alcohol is hexanol, myristyl alcohol or absolute ethanol. 19. The pharmaceutical composition of claim 18, wherein the alcohol is absolute ethanol or hexanol. 20. The pharmaceutical composition of any one of claims 12 to 19, wherein the pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant is normal saline. 21. The pharmaceutical composition of any one of claims 12 to 20, further comprising a polyhydric alcohol of the formula: CH 2 I)m-H2 R4 R5 R6 where m 1-15, 30 p 0-15, R 4 is stearic acid, palmitic acid, oleic acid, nitro or H R$ is stearic acid, palmitic acid, oleic acid, nitro or H R 6 is a choline ester of phosphoric acid, nitro, H, sodium phosphate or potassium phosphate. 22. The pharmaceutical composition of claim 21, wherein the polyhydric alcohol is selected from the group consisting of glycerol, lecithin, nitroglycerin, potassium Sglycerophosphate, sodium glycerophosphate and mixtures thereof. S' lPriv2h\0033:TCWaGSA -29- 23. The pharmaceutical composition of claim 22, wherein the polyhydric alcohol is glycerol. 24. The pharmaceutical composition of any one of claims 21 to 23, wherein the components of the composition, hereinafter designated PIG, are in the following ratio ranges: about 20 to about 80% 'y volume glycerol; about 10 to about 60% by volume absolute ethanol; and about 5 to about 15% by volume glacial acetic acid. The pharmaceutical composition of claim 24, wherein the ratio is: 6 volumes glycerol; a 3 volumes absolute ethanol; and 1 volume glacial acetic acid. 26. A pharmaceutical composition, hereinafter designated P2G, comprising: volumes of PIG as defined in claim 25 and 5 volumes of normal saline.
2. 27. A method of treating cellular and humoral disturbances in a host requiring such treatment comprising administering to said host an effective amount of the acidic composition of any one of claims 1 to 10 or .claim 11 or the acidic pharmaceutical composition of any one of claims 12 to 25 or claim 26. 28, The method of claim 27, wherein the administation route is oral, rectal, 20 transdermal, subcutaneous, intravenous or intramuscular. 29, The method of claim 27 or 28, wherein the effective amount for intravenous injection is 1ml, 12 hourly for 7 days.
3. 30. The method of claim 27 or 28, wherein the effective amount for intramuscular injection is 3ml, 12 hourly for a total of 25 31. A method of killing microorganisms in a host, comprising administering to said host an effective amount of the acidic composition of any one of claims 1 to 10 or claim 11 or tne acidic pharmaceutical composition of any one of claims 12 to 25 or claim 26.
4. 32. A method of killing microorganisms in a body fluid, comprising adding to said S* 30 body fluid an effective amount of the acidic composition of any one of claims 1 to 10 or claim 11 or the acidic pharmaceutical composition of any one of claims 12 to 25 or claim 26.
5. 33. A method of treating fungi at a locus, comprising applying to said fungi at a locus a fungicidally effective amount of the acidic composition of any one of claims 1 to 35 10 or claim 11 or the acidic pharmaceutical composition of any one of claims 12 to 25 or claim 26.
6. 34. A method of killing microorganisms in a substance comprising mixing the substance with an effective amount of the acidic composition of any one of claims 1 to IPriv2\OOO33;TCW 0LSS^ or claim 11 or the acidic pharmaceutical composition of any one of claims 12 to 25 or- claim 26. A method of killing microorganisms on a substrate comprising applying to the surface of the substrate an effective amount of the acidic composition of any one of claims 1 to 10 or claim 11 or the acidic pharmaceutical composition of any one of claims 12 to or claim 26.
7. 36. An acidic composition for killing microorganisms, substantially as herein described with reference to Example 1.
8. 37. An acidic pharmaceutical composition for killing microorganisms comprising a composition as defined in claim 36 together with a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant,
9. 38. A method of treating cellular and humoral disturbances in a host requiring such treatment comprising administering to said host an effective amount of the acidic composition of claim 36 or the acidic pharmaceutical composition of claim 37. 39, A method of killing microorganisms in a host, comprising administering to said host an effective amount of the acidic composition of claim 36 or the acidic pharmaceutical composition of claim 37. A method of killing microorganisms in a body fluid, comprising adding to said body fluid an effective amount of the acidic composition of claim 36 or the acidic pharmaceutical composition of claim 37. 41, A method of treating fungi at a locus, comprising applying to said fungi at a locus a fungicidally effective amount of the acidic composition of claim 36 or the acidic S: pharmaceutical composition of claim 37.
10. 42. A method of killing microorganisms in a substance comprising mixing the 25 substance with an effective amount of the acidic composition of claim 36 or the acidic pharmaceutical composition of claim 37,
11. 43. A method of killing microorganisms on a substrate comprising applying to the surface of the substrate an effective amount of the acidic composition of claim 36 or the acidic pharmaceutical composition of claim 37.
12. 44. A method of killing microorganisms, substantially as herein described with reference to Example 2 or 3. 45, An acidic pharmaceutical composition for killing microorganisms comprising: a carboxylate compound of the formula: RiCHZCOOH 35 where R 1 is CH3(CH 2 0 15 alkyl, H, or (CH 3 2 CHCH 2 or a salt or acid salt thereof; or IPrIvI\Q00033iTCW -31 an inorganic acid; together with an alcohol of the formula: R 2 CH 2 CH 2 OR 3 where R 2 is C 1 -C 16 alkyl, H, R(OCH 2 CH 2 )q-1, or R 3 is H; R is CI-C 20 alkyl; and q is 2 to 10; or an alcohol selected from the group consisting of benzyl alcohol, chlorbutol, chlorocresol, creosol phenethyl alcohol and phenol; with the provisos that when the alcohol is ethanol it is absolute ethanol and the composition does not include a quick breaking foam agent, except when said quick breaking foam agent is an aliphatic alcohol of the formula R 2 CH 2 CH 2 OR 3
13. 46. An acidic pharmaceutical composition for killing microorganisms comprising: a carboxylate compound of the formula: RICH 2 COOH where R 1 is CH 3 (CH 2 0 o 15 alkyl, H, or S (CH 3 2 CHCH 2 0 S 20 or a salt or acid salt thereof; or an inorganic acid; together with an alcohol of the formula: R 2 CH 2 CH 2 OR 3 S* 25 where R 2 is CI-C 1 6 alkyl, H, R(OCH2CH2)q.i, or 0 9 R 3 is H; R is CI-C20 alkyl; and q is 2 to 10; or 30 an alcohol selected from the group consisting of benzyl alcohol, chlorbutol, chlorocreosol, creosol phenethyl alcohol and phenol; with the provisos that the composition is not for topical application and when the alcohol S N^ is ethanol it is absolute ethanol. IPr Iv2loV00033:TCW0sA 32
14. 47. An acidic pharmaceutical composition for killing microorganisms comprising: a carboxylate compound of the formula: RICH 2 COOH where R, is CH 3 (CH 2 0 15 alkyl, H, or (CH 3 2 CHCH 2 0 P or a salt or acid salt thereof;, or an inorganic acid; together with (ii)(a)an alcohol of the formula: R 2 CH 2 CH 2 OR.I where R 2 is C 1 -C 1 6 alkyl, H, R(OCH 2 CH 2 )q. 1 R is CI-C 20 alkyl-; q is 2to10; or an alcohol selected from the group consisting of benzyl. alcohol, chiorbutol, chiorocreosol, creosol phenethyl alcohol and phen ol; and a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant with the proviso that the composition does not include a quick breaking foam agent, except when said 20 quick breaking foam agent is an aliphatic alcohol of the formula R 2 CH 2 CH 2 OR 3 48, An, acidic pharmaceutical composition for killing microorganisms comprising: a carboxylate compound of the formuh,: RICiH 2 COOH where R, is CH 3 (CH 2 0 15 alkyl, H, or (CN 3 2 CUCfH 2 S* GOO 0 or a salt or acid salt thereof; or an inorganic acid; together with an alcohol of the formula: &too 30 R 2 CHI{ 2 CfJ 2 OR 3 where R 2 is C 1 -C 16 alkyl, H, R(OCH 2 CTli 2 )q1 SIPIv2M00O33.TCMQ$A -33- or R 3 is H; R is CI-C 20 alkyl; q is 2 to 10; or an alcohol selected from the ,roup consisting of benzyl alcohol, chlorbutol, chlorocreosol, creosol phenethyl alcohol \nd phenol; and a pharmaceutically acceptable carrier, diluent, excipiknt and/or adjuvant with the proviso that the composition is not for topical application.
15. 49. The composition of any one of claims 45 to 48, wherein the pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant is normal saline. The composition of any one of claims 45 to 49, wherein the carboxylate is selected from the group consisting of 4-(2-methylpropyl)benzeneacetic acid, stearic acid or acetic acid and salts or acids thereof and mixtures thereof. 51, The composition of any one of claims 45 to 50, wherein the carboxylate is acetic acid. 52, The composition of claim 51, wherein the carboxylate is glacial acetic acid,
16. 53. The composition of any one of claims 45 to 49, wherein the inorganic acid is selected from sulphuric acid, acid, acid, phosphorous acid, hydrochloric acid, nitrous acid, bromic acid, iodic acid or sulphurous acid, 1 20 54, The composition to any one of claims 45 to 53, wherein the alcohol is selected from the. group consisting of hexanol, phenethyl alcohol, polyoxyethylene alcohols, S propyl alcohol, stearyl alcohol, myristyl alcohol, ethanol and mixtures thereof. S 55. the composition of claim 54, wherein the alcohol is hexanol, myristyl alcohol or absolute ethanol. 56, The composition of claim 55, wherein the alcohol is absolute ethanol or hexanol, 57, The composition of any one of claims 49 to 56, wherein the components of the composition, hereinafter designated PI, are in the following ratio ranges: t about 20 to about 80% by volume normal saline; S 30 about 10 to about 60% by volume absolute ethanol; and about 5 to about 15% by volume glacial acetic acid, 58, The composition of claim 57, wherein the ratios are: 6 volumes normal saline; 3 volumes absolute ethanol; and 35 1 volume glacial acetic acid.
17. 59. The composition of any one of claims 47, 48, or 49 to 58, further comprising a polyhydric alcohol of the formula: IPrlv2000v33TCWMSA 34 Hz2-(CH)p-( H)m-CHz R4 x5 R6 where m 1-15, p 0-15, R 4 is stearic acid, palmitic acid, oleic acid, nitro or H R 5 is stearic acid, palmitic acid, oleic acid, nitro or H R 6 is choline ester of phosphoric acid, nitro, H, sodium phosphate or potassium phosphate. The pharmaceutical composition of claim 59, wherein the polyhydric alcohol is selected from the group consisting of glycerol, lecithin, nitroglycerin, potassium glycerophosphate, sodium glycerophosphate and mixtures thereof.
18. 61. The pharmaceutical composition of claim 60, wherein the polyhydric alcohol is glycerol,
19. 62. The pharmaceutical composition of any one of claims 59 to 61, wherein the components of the composition, hereinafter designated PIG, are in the following ratio ranges: about 20 to about 80% by volume glycerol; S" about 10 to about 60% by volume absolute ethanol; and about 5 to about 15% by volume glacial acetic acid. 63, The pharmaceutical composition of claim 62, wherein the ratio is: 6 volumes glycerol; 3 volumes absolute ethanol; and 1 volume glacial acetic acid.
20. 64. A pharmaceutical composition, hereinafter designated P2, comprising: volumes of PI as defined in claim 58 and 5 volumes of normal saline, S 25 65, A pharmaceutical composition, hereinafter designated P2G, comprising: volumes of PIG as defined in claim 63 and 5 volumes of normal saline,
21. 66. A method of killing microorganisms in a host, comprising administering to said host an effective amount of the acidic pharmaceutical composition of any one of claims 45 to 63 or claim 64 or claim
22. 67. A method of killing rlicroorganisms in a body fluid, comprising adding to said body fluid an effective amount of the acidic pharmaceutical composition of any one of S claims 45 to 63 or claim 64 or claim
23. 68. A method of treating fungi at a locus, comprising applying to said fungi at a locus a fungicidally effective amount of the acidic pharmaceutical composition of any one of claims 45 to 63 or claim 64 or claim IPfrlvkIoO33:TCW 35
24. 69. A method of illing microorganisms in a substance comprising mixing the substance with an effective amount of the acidic pharmaceutical composition of any one of claims 45 to 63 or claim 64 or claim Dated 7 April, 1993 Butris Danha Iwassi Pater Attorneys for the Applicant/Nominated Person SPRUSON FERGUSON 100 0 00 0 0 0 a S 0 0 00 S 0 0 0 0 0000 *0 0 00~ S S 000000 0 IPrI~2I~OOO3~TCW C,