CA1326446C - Substance or pharmaceutical or cosmetic composition inhibition or destroying at least one unicellular living creature and/or at least one virus, drug or product containing such a substance, process of manufacture of such substance, chemical compound included in such substance, and process of inhibition or destruction of at least one... - Google Patents

Abstract

ABSTRACT Substance inhibiting or destroying at least one unicellular living creature or virus in particular such as protozoan, microbe, bacterium, gamete, fungus or other, characterized in that it comprises at least one basic active ingredient inhibiting or destroying said unicellular living creature or virus, and at least one basic active ingredient inhibiting or destroying said unicellular living creature or virus and at least one enzyme associated to said living creature or virus, said latter ingredient being an activator -preferably having a synergistic effect- of said former basic active ingredient.

Description

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The invention relates to the inhibition or destruction of unicellular living creatures such as protozoa, microbes, bacteria, gametes, fungi or others, and viruses.
Consequently, it aims in particular at the technical fields of local contraception, of antibiotherapy, antisepsis, as part of either pharmacy or cosmetic and of disinfection.

Hereafter, the term "inhibition" of a unicellular living creature or of a virus means either hindering its proliferation, or making it incapable of accomplishing some functions that it usually accomplishes. The term "destroying" means killing the unicellular living creatures or viruses.

With regard to the invention, the term "substance" hereafter means any chemical compound or association of chemical compounds having at least one given function or one function common to the compounds, and which can be included in the composition of a finished product, generally associated with one or more excipients and possibly with other substances.
Similarly, the term "product" means a usable finished product. Thus, a finished product is generally constituted of at least one excipient and of several substances, each substance being constituted of one or several chemical compounds having similar or identical functions. The ter~
"substance" may correspond to an actual fact, but may be .~
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purely theoretical and functional in the case of intricate mixtures where the compounds have multiple effects or which effects interfere with each othex. The functional classification in compounds, substances, products does not necessarily correspond to the process of manufacture of the product and to the mixture actually obtained in the practice.
As usual, the term "composition" is used here and in all the following text to design a pharmaceutical or cosmetic substance.

Substances inhibiting or destroying unicellular living creatures, either in the biological, pharmaceutical, cosmetic fields, or even in broader fields such as disinfection or others, are already known.

In particular, spermicidal compositions are known from US
Patents 4 339 441 and 4 35i 475.

Numerous chemical compounds usable in local contraception methods for living beings are also known. In particular, it is known that surfactants lowering the interfacial tension ~e.g. quaternary ammoniums, nonoxynols, derivatives of amidoethylglycinate on ~atty acids, methyltauride sodium oxysalt ...) and some other compounds such as phenylmercuric nitrate, para-menthanylphenylpolyoxyethylene ether or ~

-1 3 2 ~

;.
trisodium salt of polysaccharide sulphuric ether, have . inhibiting or destroying effects on unicellulax living creatures, in particular have spermicidal effects~

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~:~ 5 Substances mechanically acting on the spermatozoa, for s example by immobilizing them, are also known. U.S. patent .~ 4 368 186 describes such effects, and more particularly the association of "poloxamer" with spermatozoa inhibiting agents, in view of controlling gelation and solubilization of the products and thus mechanically increasing the efficiency ~ of the inhibiting agents with an additive or a synergistic ~ effect.

, Locally contraceptive compositions are also known, particularly spermicidal ones, including such chemical compounds and which . .

~' ... :

13~6~ 3 are locally usable for inhibiting the fertilization ability of gametes, particularly of spermatozoa of human or animal beings.

These known compositions include a concentration of inhibiting chemical compound superior to the minimal inhibiting concentration, called MIC, in solution or suspended in a pharmaceutically acceptable excipient which depends on the galenical form used. It is known that in order to have all the spermatozoa which are contained in 0.2 milliliters of sperm killed in less than S seconds (conditions of the total spermicidal test according to the standards of IPPF, International Planned Parenthood Federation), the concentration of the spermicidal active ingredient in 1 milliliter of pharmaceutical composition must be superior or equal to the minimal inhibiting concentration, called MIC, of this active ingredient. The MIC of a chemical compound depends on this compound, but also on the conditions in which it is used, i.e. on the galenical form including the composition.

More generally, pharmaceutical or cosmetic compositions including at least one basic active ingredient inhibiting or destroying at least one unicellular living creature and drugs or cosmetic products including such compositions are known.

In the field of antisepsis and disinfection, numerous active ingredients are known : halogens (chlorinated or iodinated derivatives ...), aldehydes, alcohols, phenols, acids, metals ~silver, copper, mercury, zinc salts ...), amidines, biguanides, diphenylurea, oxydants (hydrogen peroxide, potassium permanganate ...), colouring agents, agents lowering the interfacial tension and wetting agents ~cationic, anionic, amphoteric or organic).

Antiseptic and/or disinfectant and/or antiprotozoal and/or antifungal and/or antibiotic and/or antiviral products including such inhibiting or destroying substances, and manufacturing processes of these substances or compositions, are also known.

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The known substances or compositions are generally satisfactory but set some problems for their practical use.
, These problems are essentially the following :

First of all, it is generally desirable to obtain a total inhibition or destruction efficiency of the unicellular living creature(s~ or of the virus(es), i.e. an inhibition or de~truction rate of 100% in the practical application circumstances. Well, this is not always the case when no strict precautions for use are taken, or when a limitation of the doses of active ingredient are required (for example in the ca6e of the cosmetic).

Moreover, it is generally desirable to exhibit an activity against one or more given unicellular living creatures or viruses, e.g. gametes or pathogens, without giving rise to ~hort-term and/or long-term undesirable side effects (activlty against other unicellular living creatures, irritations, damages to the environment...). But, in the practice, it has been found that the doses required for solving the first above mentioned problem give rise to long-term side effects (generally linked to regular u6e), and even to short-term side effects (use by fits and starts). In the medical field, some teratogen and/or cancerigen effects have `.A

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been noted from certain threshold doses and with certain active ingredients. In the field of disinfection, some undesirable effects may be noted against the materials to be disinfected.

The invention increase~ the inhibiting or destroying ability of a substance or composition including a given limited concentration of basic inhibiting or destroying active ingredient, without increasing this concentration.

~he invention reduces the concentrations of the basic active ingredients without decreasing the inhibiting or destroying ability of the substance or composition for all that and in order to avoid the side effects and to better control the selectivity towards the various unicellular living creatures and viruses.

In particular, the invention furnishes a new pharmaceutical or cosmetic composition, more particularly locally contraceptive and a drug or product including such a composition, which may be used either by fits and starts, or regularly and continuously at long-term, without risking side effects such as teratogen or cancerigen, and which efficiency i8 total, i.e. which percentage of failures is statistically null or insignificant, and this within the regular mere circumstances of use (with no particular precautions).

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Moreover, the invention furnishes a locally contraceptive pharmaceutical product, easy to use and totally efficient, i.e. which gives some results similar to those of the oral contraception without having the drawbacks thereof.
S
The invention also provides a chemical compound usable in a - local contraception method.

The invention also reduces the doses of the active ingredients inhibiting or destroying unicellular living creatures or viruses in the drugs, cosmetic products, or disinfectant products, especially in the antiseptic, antibiotic, bactericidal, antiprotozoal, antifungal, spermicidal, antiviral ... products.

The invention relates to a substance inhibitinq or destroying at least one unicellular living creature or virus in particular such as protozoan, microbe, bacterium, gamete, fungus or other, characterized in that it comprises at least one bas~c active 1326~ 6 ., ingredient inhibiting or destroying said unicellular living creature or virus, and at least one ingredient inhibiting or destroying at least one enzyme associated to said living creature or virus, said latter ingredient being an activator -preferably ~ r having a synergistic effect- of said former basic active : ingredient.

Preferably, the ingredient inhibiting or destroying at least one associated enzyme, called hereafter "activating ingredient" or activator" is an agent hindering the working of the couple enzyme/substrate.
:
~ut it has been surprisingly found that such an agent could advantageously be formed with fluoride anion F emitted from a fluorinated compound, either spontaneously, or after enzymic action. It has also been found that, in some cases, the basic active ingredient itself is capable of emitting an activating ingredient, and/or that the activating ingredient itself is an active ingredient inhibiting or destroying at least one unicellular living creature or virus.

More precisely, it has been noted that such a fluorinated compound has by itself an ability for inhibiting or destroying unicellular living creatures and viruses, and that such a fluorinated compound has a synergistic effect with the associated basic active ingredient(s).
.
feature of the invention is to provide a local contraceptive composition, more particularly spermicidal composition, characterized in that it comprises at least one chemical compound capable of emitting fluoride anion F , as an active ingredient inhibiting or destroying gametes, directly or by potentiation, and an excipient.

The invention also provides a drug, an antiseptic and/or disinfectant -more particularly locally antiseptic-, andlor antiprotozoal -more particularly locally antiprotozoal-, and/or bacteri~ide -more particularly locally bactericide-, and/ox antifungal -more particularly locally antifungal-, and/or .
. .

1 3 2 ~ 7 antibiotic -more particularly locally antibiotic-, and/or antiviral product, a cosmetic product -more particularly local cosmetic ~uch as a synthetic soap or milk- and a contraceptive prodl~t which is locally applied in contact with gametes -more particularly ovule, cream, gel, solution, foam, tablet, soluble waffle, tampon, vaginal suppository- characterized in that they comprise a substance or a composition according to the invention.

Here and hereafter, the term N local" and its derivatives means that the product is used at a predetermined place to be treated, e.g. the vagina or other anatomic parts, so that the effect is produced in the environment near this place, against unicellular living creatures or viruses that come into contact with the product, and this in opposi~ion to general administrations (e.g.
oral administration or parenteral administration).

A substance, a composition, a drug, a product, a chemical compound according to the invention are as well directed to local administrations as to general administrations. For example, a spermicide according to the invention may be locally applied.
~esidos, when wishing to overcome the resistance effects of the pathogenic unicellular living creatures against the regular therapies, one would rather use general administrations of the invention.

The invention is also concerned with the use in a cosmetic product of a composition including at least one basic active ingredient and at least one fluorinated chemical compound capable of emltting fluoride anion F- as active ingredient of said basic active ingredient~s) ; with the use of a fluorinated chemical compound capable of emitting fluoride anion F for manufacturing a substance including at least one basic active ingredient, as activor of said basic active ingredient ; with the use of a substance or a composition according to the invention in the manufacture of a drug to be used as antibiotic and/or antiprotozoal and/or bactericide and/or antifungal and/or antiseptic andlor antivival; and with the use of a substance ox a composition according to the invention in the manufacture of a local contraceptive for human or animal being, in particular ---` 1326~ 8 inhibiting or destroying gametes.

The invention also provides a manufacturing process of a substance or composition according to the invention inhibiting or destroying at least one unicellular living creature -in particular such as protozoan, microbe, bacteria, gamete, fungus or otSIer, virus-, characterized in that at least one basic active ingredient inhibiting or destroying said unicellular living creature or virus is mixed with at least one ingredient inhibiting or destroying an enzymatic system associated to said living creature or virus, said latter ingredient being an activator of said former basic active ingredient.

The invention also provides a chemical compound including ionizable fluorine for use in a local contraception method for living beings, more particularly in a locally contraceptive product for human or animal beings according to the invention or in a substance or a composition according to the invention.

According to the invention an activating ingredient inhibiting or destroying at least one enzyme associated to said unicellular living creature or virus induces a remarkable sensibilization of said unicellular living creature or virus to agressions from outside, in particular to the action of said basic active ingredient inhibiting or destroying said unicellular living creature or virus, by 'blocking~ the couple enzyme/substrate. It is effectively known that each unicellular living creature or virus owns a vital enzymatic system. Besides, unicellular living creatures or viruses may emit, upon some circumstances (e.g.
resistance to antibioticl, some particular enzymes providing the destruction of some aggressing agent (e.g. lactamase destroying penicillins), these enzymes being called ~protecting enzymes".
The invention lies in inhibiting the function of these enzymes, and thus fragilizing the unicellular living creature by creating the optimal conditions for the efficiency of the active ingredients against it. This brings numerous advantages compared to the prior art, which are on one hand to satisfy the aims above mentioned and, on the other hand, to be able to act ~in a selective manner upon a given unicellular living creature or upon !

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a given family of unicellular living creatures by acting upon a given enzyme or upon a given family of enzymes. In the case of viruses, the invention aims to inhibitin~ the enzyme~
that are necessary for their formation and/or their replication. Hereafter "associated enzymes" means vital and/or protecting enzymes of unicellular living creatures and/or vixuses.

The inventors have determined that fluorine in the ionized state F- has a particularly efficient and benefit effect as activating ingredient against the associated enzymes, and this under trifling regular concentrations. Moreover, ionized fluorine F- is very common, economical and relatively easy to use. Its manipulations and utilizations are well controlled, as well as the side effects that he may provide according to the doses used.

The invention provides a process of inhibition or destruction of at least one unicellular living creature or virus -in particular such as protozoan, microbe, bacterium, gamete, fungus or other-, characterized by the use of at least one basic active ingredient inhibiting or destroying said unicellular living creature and at least one ingredient inhibiting or destroying at lea~t one enzyme associated to said living creature or virus, said latter ingredient being an activator -preferably having a synergistic effect- of said ~'' 1326~

former active ingredient; and such a process including the use of at least one substance or composition according to the invention.

The invention relates to the inhibition or destruction of unicellular living creatures such as protozoa, microbes, bacteria, gametes, fungi, whether pathogenic or not, and viruses. The invention has mostly two different kinds of uses: either uses in the cosmetic or pharmaceutical field (case of the following examples of spermicides or bactericides acting against pathogenic agents), or uses in more common fields such as agriculture, disinfection (following example) or others. In all 9a . . :

1326~ 10 the cases, a substance according to the invention is characterized in that it includes at least one basic active ingredient inl1ibiting or destroying said unicellular lLving crea'ure or virus, and at least one ingredient inhibiting or destroying at least one enzyme associated to said living creature or virus, said latter ingredient thus being an activator -preferably having a synergetic effect when being itself capable of inhibiting or destroying said living being or virus- of said former basic active ingredient.

The function of the activating ingredient consists in annihilating the working of the enzymatic system associated to said living creature(s) or virus~es). In this way, the inventors have found that such activating ingredient is advantageously an agent hindering the working of the couple enzyme/substrate, preferably anion fluoride F emitted from a fluorinated compound, e.g. a metallic derivative of fluorine. Some very good results have been noted with sodium fluoride, calcium fluoride, potassium fluoride, aluminium fluoride, tin fluoride, ammonium fluoride, or sodium monofluorophosphate or other. For example, the following unicellular living creatures or viruses may be concerned with the invention :

. gametes ~spermatozoa, ovula) gram-positive cocci such as staphylococci and streptococci gram-negative cocci such as gonococci qram-positive bacilli gram-negative bacilli such as colibacilli or escherichia coli acid-alcoholo-fast bacilli such as mycobacteria, e.g.
mycobacterium smegmatls splral bacteria such as spirochetes, c.g. treponema miscellaneous bacteria such as chlamydla flagellate protozoa, such as trichomonas miscellaneous yeasts such as candida albicans . viruses or retroviruses, such as HIV (Human Immunodeficiency Virus) and Herpes.

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, For example : the following enzymes associated to at least one such unicellular living creature or virus may be concerned with the invention (Table 1) :

_ ... . _ ENZYME SU~STRATE
__ _ _ Alkaline Phosphatase 2- naphthyl phosphate Esterase (C 4) 2- naphthyl butyrate Esterase Lipase (C 8) 2- naphthyl caprylate Lipase (C 14) 2- naphthyl myristate Leucine arylamidase L- leucyl -2- naphthylamide Valine arylamidase L- valyl -2- naphthylamide Cystine arylamidase L- cystyl -2- naphthylamide Trypsin N- benzoyl -DL- arginine -2-naphthylamide Chymotrypsine N- glutaryl-phenylalanine

-2- naphthylamide Acid phosphatase 2- naphthyl phosphate Naphthol-AS-B1- Naphthol-AS-B1- phosphate phosphohydrolase a galactosidase 6-Br-2- naphthyl ~ D-galactopyranoside galactosidase 2- naphthyl -~D-galactopyranoside glucuronidase naphthol-AS-~ D-qlucuronide glucosidase 2- naphthyl-~D- glucopyrano-side glucosidase 6-Br-2- naphthyl-~D-glucopyranoside N- acetyl -~ glucosaminidase 1- naphthyl-N-acetyl-~D-glucosamimnide mannosidase 6-Dr-2- naphthyl-~D-mannopyranoside fucosidase 2- naphthyl-~L-fucopyranoside ~326~ 12 A basic active ingredient used in a substance or composition according to the invention is for example a cationic or anionic or ~mphoteric or non-ionic surfactant lowering the interfacial tension, preferably a quaternary ammonium. Benzalkonium chloride or other alkylbenzalkonium is an example of cationic surfactant.
A methyltauride sodium oxysalt is an example of anionic surfactant. A derivative of amidoethylglycinate on fatty acids is an example of amphoteric surfactant. A nonoxynol is an example of non-ionic surfactant. The basic active ingredient may also advantageously be phenylmercuric nitrate or para-menthanyl-phenylpolyoxyethylene ether or a trisodium salt of polysaccharide sulfuric ether or other (halogen, aldehyde, alcohol, phenol, acid, metal, amidine, biguanide, diphenylurea, oxydant, colouring agent ...).

In the various tested uses, it has been shown that the alone activating ingredient alone has generally by itself also an activity directly against said unicellular living creature or virus. It has then surprisingly been noted that the association of the activating ingredient with the basic active ingredient has a synergistic effect in so far as the results obtained are not only corresponding to the sum of the results expected from the only presence of the basic active ingredient and of the activating ingredient, but, on the contrary, are superior to this sum.

The efficiency of such active ingredients or activators can be measured with the minimal inhibiting concentration called MIC
which corresponds to the concentration of the active ingredient inducing the inhibition or the death of the whole unicellular living creatures or viruses in a given time.

Advantageously, in a substance according to the invention, the anion fluoride F concentration emitted by the activating fluorinated compound is inferior to the minimal inhibiting concentration ~MIC) of fluoride anion F without basic active ingredient.

1326~ 3 Similarly, the basic active ingredient concentration in a substance according to the invention can be inferior to the minimal inhibiting concentration (MIC) of this basic active ingrodient without activating ingredient. Even so and surprisingly, such a substance, according to the invention, has a total efficiency, i.e. at least equal to the one of substances including either only fluoride anion F in a concentration superior or equal to its MIC, or only a basic active ingredient in a concentration superior or equal to its MIC.
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Besides, the basic active ingredient itself may also be capable of emitting an activating ingredient, such as fluoride anion F .
A substance or a composition according to the invention may include several basic active ingredients which functions may be identical or various and/or several activating ingredients acting on at least one enzyme associated to one or several of the basic active ingredients.

A substance or a composition according to the invention can be used in multiple ways for obtaining products, and according to the way of using the products, can be used in local or general administration.

Among the particularly advantageous uses of products according to the invention, the various therapeutical possible uses as drug can be mentioned. As a matter of fact, the problem of inhibition or destruction of unicellular living creatures or viruses is encountered in an always increasing number of therapeutical uses.
This may be either the fight against -~ome pathogenic agent~, and then the products are antibiotic and/or antiprotozoal and/or bactericide and/or antifungal and/ox antiseptic and/or antiviral, or even against some non-pathogenic agents such as gametes, e.g.
spermatozoa within the framework of contraception, in particular local contraception.

A substance or a composition according to the invention can also advantageously be used in a cosmetic product with such doses and concentrations that do not permit its classification as a pharmaceutical product.

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As a matter of fact, for example, the efficient concentrations of fluorinated chemical compounds and even of basic active ingredients can be lowered in such an extent that they become inferior to the threshold values separating the pharmaceutical and cosmetic fields, and thiæ without lowering the efficiency of the product by this way.

A substance or a composition according to the invention can also be used in products which are neither cosmetics nor pharmaceutical products, for example as antifungal, antiprotozoal, antiseptic, antibiotic or other in the field of agriculture, or also in the field of the disinfection of surfaces.

The preferred embodiment of the invention presently known is the one of the products locally used on the genitals of male and/or female mammals, as spermicides and/or bactericides for fighting against sexually transmissible diseases (STD).

Benzalkonium chloride and nonoxynol 9 are preferably used as active ingredient. Any metallic derivative of fluorine, e.g.
sodium fluoride is preferably used as activating ingredient.
All the known galenical forms are usable, such as preferably ovule, cream, gel, solution, foam, tablet, soluble waffle, tampon, vaginal suppository or others.

1~26~6 The proportions to be used of active and activating ingredients depends on the galenical form since only the actual concentrations induced in vivo are important as . regards to the efficiency of the product.

These proportions must vary between the MIC and the maximal concentrations from which side effects are induced. In local administration, intolerances (irritations) of the treated parts 14a ' `~ ~326~Q~ 15 must be avoided. In general administration, toxic concentrations must be avoided.
;

' Thus the ~enzalkonium Chloride concentration in vivo i5 preferably 1.2 ~ (in weight) and the fluoride anion F
concentration in vivo is preferably 0.5 '~ (in weight).

Several preferred embodiments of the invention are hereafter described, in several tested uses, by referring to tests carried out on several unicellular living creatures.

.:
I) USE OF THE INVENTION FOR LOCAL CONTRACEPTION :
_____~______________________________________ The invention advantageously provides a spermicidal pharmaceutical product locally applied so that it comes into contact with sperm and kills or inhibits the~spermatozoa.

A spermicidal pharmaceutical product according to the invention may be presented under various galenical forms : tablet, ovule, soluble, creaml gel, soluble waffle, tampon, foam, vaginal suppository, inserted within the vagina before sexual intercourse for preventing a fertilization by killing or inhibiting the spermatozoa before they come into contact with the ovula .

A product according to the invention comprises a composition which includes at least one chemical compound according to the invention which includes ionizable fluorine, i.e. capable of emitting fluoride anion F , as an active ingredient spermicidal directly or by potentiation.

A chemical compound according to the invention is capable of emitting fluoride anion F when soluted, in particulax in aqueous solution. For example, it is constituted of a metallic derivative of fluorine such as sodium fluoride, calcium fluoride, potassium fluoride, aluminium fluoride, tin fluoride, ammonium fluoride, sodium monofluorophosphate ..., or an organic fluorinated compound such as a fluorinated amine.

~ ~3~ 16 For example, for measuring the spermicide activity of a chemical compound, one may use the total spermicidal test according to the stan~ards of IPPF, which consists in finding the minimal inhibiting concentration called MIC texpressed with a weight percentage) of the chemical compound in one milliliter of solution inducing the death of all the spermatozoa which are contained in 0.2 milliliter of sperm in less than 5 seconds. The test is carried out on at least 6 sperms from various donors, satisfying the following minimal conditions from IPPF :

age of the sample : two hours ;
density per mm3 : 50 million spermatozoa ;
mobility : 50 % of the spermatozoa should move forward fastly when examined at 35 -37 C in a recent sample ;
viscosity : ejaculum conveniently liquefied, not filaceous and homogeneous-looking with the naked eye ;
collected in sterile glass tubes hermetically closed, preserved at 37- C.
!

The inventors have found that, under these conditions, fluoride anion F has a spermicide activity of 100 ~ according to the IPPF
test when present at a titer of 5 ppm (e.g. S milligrams per liter).

A pharmaceutical spermicidal composition according to a first variant of the invention includes at least one f1uorinated chemical compound capable of emitting fluoride anion F as unique active inhibiting or destroying ingredient. The titer of F- in the composition is advantageously superior to 4.5 ppm, preferably about S ppm when a 100 % inhibiting composition is desired.

Moreover, the inventors have found that fluoride anion F-, in addition to this direct spermicide activity, has a spermicide activity by potentiation of known spermicidal compounds.
Therefore, a composition according to the invention is advantageously constituted on one hand of at least one basic active spermicidal ingredient such as a cationic, or anionic, or amphoteric or non-ionic surfactant lowering the interfacial ~ ` 1326~ ~ 17 tension, or even para-menthanylphenylpolyoxyethylene ether or a trisodium salt of polysaccharide sulfuric ether or other, on second hand of at least one fluorinated compound according to the invention capable of emitting fluoride anion F , and finally of a pharmaceutical excipient and various common additives (anti-oxydant, ...).

In a composition according to the invention, the basic active ingredient concentration may be inferior to the MIC of this basic active ingredient without ion F , the composition being nevertheless 100 % inhibiting, i.e. satisfying the total spermicidal test of IPPF. A composition according to the invention may include an admixture of several basic active ingredients inhibiting gametes and/or an admixture of several various fluorinated chemical compound.

Hereafter, the percentages are given in weight.

The preferred embodiments of the invention for its uses in local contraception are as follows :

. OVULES :
_ _ _ _ _ .
benzalkonium chloride 1.20 ~.
anion F 0.50 ~.
(e.g. sodium fluoride) Excipients : semi-synthetic glycerides or cacao butter, or gelatin or glycerin and purified water, antioxygens, antiseptics.

CREAMS AND MILK5 :
________________ , benzalkonium chloride 1.20 ~.
anion F 0.50 (e.g. sodium fluoride) Excipients : distilled or purified water, humectants, . 1326'~ 18 emulsifiers, stabilizers, antioxygens, antiseptics (to be .~ included in variable proportions according to the viscosity and pH to be obtained).
:
. OINTMENTS AND POMMADES :
______________________ benzalkonium chloride 1.20 %
anion F 0.50 %
(e.g. sodium fluoride) Excipients : distilled or purified water, emulsifier, excipients of the kind of the fatty compounds (vaseline, lanoleine, lanovaseline, stearovaseline), stabilizers, antioxygens, antiseptics (to be included in variable proportions according to the viscosity and pH to be obtained).

GEL :
_ _ _ benzalkonium chloride 1.20 ~.
anion F 0.50 s (e.g. sodium fluoride) Excipients : soluble derivatives of cellulose compatible with the cationic surfactants, distilled or purified water, glycerin, sorbitol, antioxygens, antiseptics ~to be included in variable proportions according to the viscosity and pH to be obtained).

SOLU~LE WAFFLE :
______________ benzalkonium chloride 1.20 Anion F 0.50 ~e.g. sodium fluoride) Excipients : polyvinyl alcohol, glycerin, sorbitol, propylene glycol, distilled or purified water, antioxygens.

TA~LETS :

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benzalkonium chloride 25 mg per tablet anion F 10 mg per tablet (e.g. sodium fluoride) ~.
Excipients : lactose, magnesium stearate, cellulose, amylum, citric acid, sodium bicarbonate.

SYNTHETIC SOAPS:
_______________ benzalkonium chloride 2 %
anion F 1 (e.g. sodium fluoride) Excipients : foaming and wetting products compatible with quaternary ammonia (e.g. amphoteric surfactant such as betaine or amino-betaine) emollients, stabilizers, antioxygens, antiseptics.

SOLUTIONS :
________ benzalkonium chloride 0.50 %
anion F 0.25 ~.
~e.g. sodium fluoride) Excipients : distilled or purified water, ethanol, antioxygens, glycerin, sorbitol, antiseptics (to be included in variable proportions according to the pH to be obtained).

COMPARATIVE TEST N' ~:

The MIC of various known spermicidal compounds were determined with the IPPF test. The following results have been obtained by 1 milliliter of composition reacting with 0.2 milliliter of sperm and by determininq the minimal concentration of the ~permicidal compounds that induces~ the death of all the spermatozoa in 5 - 1326~
:
seconds, and this with 6 sperms from various donors.
. . _ __ . Spermicidal compound MIC (~ in weight) .. _ ._ .~ p-menthanylphenylpolyoxyethylene ether 0 006 : _ . _ _. _ .
Trisodium salt of polysaccharide sulfuric ether 0.007 . _ .. __ ._ Anionic surfactant ; (methyltauride sodium oxysalt) _ Cationic surfactant . (benzalkonium chloride) 0.006 ., _ _ __ ._ ... _ _ .. __ . Non-ionic surfactant (nonoxynol 9) 0.006 _ _ .... _ _ .
Amphoteric surfactant . (derivative of amidoethylglycinate . on fatty acids) 0.001 ,, i:
. ,T~SJ N~ 2:
~ .
The same total spermicidal test of IPPF was carried out with 1 milliliter of composition already containing 0.0001 ~O (in weight) of fluoride anion F reacting upon 0.2 milliliter of sperm, by determining the minimal concentration of the spermicidal compounds that induces the death of all the spermatozoa in S
seconds, and this with 6 sperms from various donors.
...
Spermicidal compound MIC (S. in weight) ~ . ..
p-menthanylphenylpolyoxyethylene ether 0.003 . . . _. . _ . ___ Trisodium salt of polysaccharide : sulfuric ether 0.0025 _ .. _ .................... _ ...
Anionic surfactant (methyltauride sodium oxysalt) 0.50 . . . . _ .. __ .
Cationic .urfactant (benzalkonium chloride) 0.002 . .
Non-ionic surfactant ~nonoxynol 9) 0.003 . . ._ ~
Amphoteric surfactant (derivative of amidoethylglycinate on fatty acids) 0.0005 __ _ lt is thus noticeable that the inhibiting ability of the known ~` 1326~ 21 spermicidal ingredients is much improved with the adjunction of ionizable fluorine in the composition. A composition according to the invention may therefore contain very little basic active spermicidal ingredient, in particular in a concentration inferior to the minimal inhibiting concentration of this active ingredient without ion F .

Moreover, the concentration of ion F associated to a basic active ingredient may also be very low, in particular inferior to the minimal inhibiting concentration of fluoride anion F .

As an example, the inventors have found that when a solution containing 0.003 % of benzalkonium chloride and a solution containing 0.0001 ~ of fluoride anion F each do not have a total spermicide activity according to the IPPF test, a solution containing 0.003 ~ benzalkonium chloride and 0.001 ~ of fluoride anion F both together does satisfy the IPPF test. A synergistic effect is therefore observed.

TEST N' 3:

This test consists in realizing a test identical to tests N' and 2 above mentioned, but in presence of sodium borate, in order to complex ion F- : the spermicidal effect of ion F- has totally disappeared, thus demonstrating that only ion F is active or potentiator of the spermicidal effect.

T~ST N- 4:

Under the same conditions previously described ~Tests N- 1 to 3), various perfluorinated benzalkonium chlorides were used as basic spermicidal compounds. It was thus shown that perfluorinated benzalkonium chlorides have a spermicide activity similar to the one of the mere benzalkonium chloride. Besides, this activity remains identical to itself under the conditions of test N' 3, in 1326~ 22 presence of sodium borate, which demonstrates that fluorine fixed on the benzine nucleus was not ionized.

Test N- 2 was also realized on perfluorinated benzalkonium chloride mixed with another chemical compound capable of emitting ion F . The potentiation of the spermicide activity of the perfluorinated benzalkonium chloride was also observed. This same test realized in presence of sodium borate (according to test N- 3) did induce a spermicide activity which is the one of perfluorinated benzalkonium chloride.

These two tests N- 3 and 4 show that the potentiation of the basic active ingredient only takes place in presence of fluoride anion F .

For manufacturing a spermicidal pharmaceutical product according to the invention, a solution with a given concentration in fluoride anion F and, eventually, in basic active ingredie~t is realized and integrated in the excipient chosen according to the galenical form which is intended to be manufactured. In the case of the tablet, the basic active ingredient and the chemical compound capable of emitting ion F are integrated to the excipient in the form of primary products.

COMPARATIVE TEST N- 5:

This test in vi~ro was conducted on galenical preparations including benzalkonium chloride as basic active ingredient, by determining the MIC of this benzalkonium chloride after simulation in vitro of the actual conditions in vivo (extraction, solubilization ...).

This test conducted without activating ingredient indued the following results :

- 1326~Q6 23 MIC (~ in weight) .` Galenical form of benzalkonium

3 chloride .~ _ .. _ .
3 , ovule 0.0063 ~ cream 0.0083 s Tampon 0.0075 Tablet 0.0095 , Soluble waffle 0.0080 Gel 0.0080 The percentages correspond to the proportions (in weight) of benzalkonium chloride in the solution used in vitro for the spermicidal test according to IPPF and obtained after simulation, the proportions being measured by titrating using a sample taXen j~ off from the solution.
. !
TEST N 6:

The same conditions as during the comparative test N' 5 were used, but from galenical forms each originally containing 0.45 ~.
(in weight) of fluoride anion F .

The following results were obtained :
__ : MIC ~ in weight~
Galenical form of benzalXonium ; chloride . .
ovule 0.0023 Cream 0.0030 Tampon 0.0025 Tablet 0.0025 Soluble waffle 0.0017 Gel 0.0033 .

~` 1 3 2 6~ ~ S 24 II) USE OF THE INVENTION FOR ANTISEPSIS, ANTIBIOTICS, ... AND IN
__ ____ _____ ____ ________________ ____ __ _____ __ PARTICULAR FOR FIGHTING AGAINST THE STD : , __ __ __________ ____________ .___ The preferred embodiments of the invention for its use, e.g. as antiseptic in dermatology are the following ones : !

. CREAMS AND MILKS :
____ __ _______ benzalkonium chloride 1.20 3 anion F 0.50 3 (e.g. sodium fluoride) Excipients : distilled or purified water, humectants, emulsifiers, stabiliæers, antioxygens, antiseptics (to be included in variable proportions according to the viscosity and pH to be obtained).

OINTMENTS AND POMMADES :
_______ _ ___ ___ benzalkonium chloride 1.20 %
anion F 0.50 3 ~e.g. sodium fluoride) Excipients : distilled or purified water, emulsifiers, excipients of the kind of the fatty compounds (vaseline, lanoleine, lanovaseline, stearovaseline), stabilizers, antioxygens, antiseptics (to be included in variable proportions according to the viscosity and pH to be obtained).

SYNTHETIC SOAPS :
__ __ ___ __ _ .
benzalkonium chloride 2 3 anion F 1 s, (e.g. sodium fluoride) ^" ~3~ 25 Excipients : foaming and wetting products compatible with quaternary ammonia (e.g. amphoteric surfactant such as . betaine or amino-betaine) emollients, stabilizers, ~ - antioxygens, antiseptics.

. SOLUTIONS :
_____ benzalkonium chloride 0~50 %
anion ~~ 0.25 %
~e.g. sodium fluoride) ~:, " Excipients : distilled or purified water, ethanol, antioxygens, glycerine, sorbitol, antiseptics (to be included in variable proportions according to the pH to be obtained~.

~`
The preferred embodiments of the invention for its use, e.g. as . local antibiotic in dermatology are the following ones :

SOLUTION :

erythromycine base 4 ~
anion F O.5 S.

Excipients : ethyl alcohol, propylene glycol, distilled : water.

~ . GEL :
J _ _ _ erythromycine base 4 anion F 0.5 Excipients : ethyl alcohol, hydroxypeopylcellulose, distilled water, glycerine. I

POMMADES :

neomycin base 0.35 t ~`
':

il ~ 2 ~ 26anion F 0.50 %
or bacitracin 50.000 IU ~O
anion F 0.50 's or oxytetracycline chlorhydrate 3 s anion F 0-50 %
or aureomycin chlorhydrate 1 %
anion F 0.50 %

Excipients : vaseline, vaseline oil, lanoline.

CREAMS :
_ _ _ soframycin sulfate 2.5 s anion F 0 50 3 , Excipients : propylene glycol, polyoxyethyleneglycol, distilled water.

The preferred embodiments of the invention for its use, e.g. as local antibiotic in otorhinolaryngology are the following ones :

. OPHTALMIC POMMADES :
_____________ ____ aureomycin anion F 0.50 s or oxytetracycline 0.50 s anion F 0.25 Excipients : vaseline, vdseline oil, lanoline NASAL SOLUTIONS :
_ _ _ _ _ _ _ _ soframycin sulfate 1.25 anion F 0.50 -- 132~ 27 Excipients : distilled water, citric acid, sodium chloride.

.
For increasing the activity of the local antibiotherapeutical ; preparations, 0.10 % of benzalkonium chloride may advantageously be added.

The preferred embodiments of the invention for its use, e.g. in gynecology and more particularly for fighting against the sexually transmissible diseases STD are those described under the item "USE OF THE INVENTON FOR LOCAL CONTRACEPTION" and under the denominations "OVULES", "CREAMS", "OINTMENTS AND PO~MADES", "GELS", "TA~LETS", "SYNTHETIC SOAPS" and ~SOLUTIONS".

The methodology used in the tests conducted for those uses of the invention was as follows :

. for Neisseria Gonorrhoeae :

The used germs come from hospital isolations - dilution range of the substances to be tested :
Solvent : bidistilled sterile H2O
Range with geometrical ratio of 2 Doses : from 2000 to 1.56 ~and less) ~g/ml 2 ml of each of the dilutions are mixed with 18 ml of solid preferable culture medium : gelose medium for isolation of gonococci (Institut Pasteur) enriched with G supplement :

Formula : . Poulain serum 165 ml yeast extract 100 ml globular extract 235 ml glucose 0.65 ml `` ~` 132~ 28 . distilled H20 to make up fvr S00 ml -- Culture medium of the gonococci : 2000 ml of Pa.steur '~ medium + S00 ml of G supplement.

,~ .
Those culture medium associated to the dilutions of the active substances form the investigation mean~ of the bactericide activity. The final concentrations of the substances are about from 800 to 0.156 ~g/ml in the Petri dishes. Thc used suspensions (dilution in physiological water of a 24 hours-culture in nutritive liquid-broth medium) are placed in wells hollowed in a synthetic base under laminar-flow hood. In each of th~ prepared wells, a strain (multiple seeder) is studied. Each studied dish is examined after 2~ and 48 hours of culture (stove at 37- C).

Determination of the MIC : the gonococci strains are spreaded on plates (dilution on plate) some of them being prepared as comparative and control strains without substance to be tested.

~l of 10 formative colonies/ml are deposited on the gelose plates completed or not with the substances to be tested (18 hours culture of gonococci suspended in a Sorensen solution).

A 48 h incubation at 36- C is carried out, then the growth or the lack of growth of the gonococci is observéd on the plates.

for Candida Albican$ :

The methodology is substAntiAlly the same as for Neisseria Gonorrhoeae, but with the following differences :

- nilution range in bidistilled sterilc water from 2000 to 1.56 ~g/ml.

O.S ml of each dilution is added to 4.5 ml of liquid Roiron medium.

132~ 29 - The tubes are seeded with cultures of Candida (24 hours/Roiron medium) or with the comparative strain (Roiron medium). The incubation of the tubes i5 ; conducted in stove at 37' C during 24 and 48 hours. At t = 24 hours and t = 48 hours, observation of a drop between slide and cover-glass under microscope.

- Exp~ession of the results by accounting the yeasts and determination of the fungicide MIC. On comparative tubes, determination of the percentage in resistants.

for_Trichomonas Vaqinalis :

Same methodology as for Candida Albicans.

for ChlamYdia :

Inoculum : it is constituted by the host-cells of chlamydia or Mac Coy cells. They are preserved at - ~O C. The cellular concentration is from 2 to 2.5 x 10 cells/ml for the tests. The cellular layer is prepared in a complete culture medium.

The substances to be tested are diluted with an increasing range which geometrical ratio is 2 in bidistilled sterile water.

The used method i5 the one of Profes~ors F.
CATALAN, P. SEDNA~UI, A. MILOVANOVIC and al., A.
FOURNIER INSTITUTE, Paris.

1 ml of dilution of the substances to be tested is mixed with 1 ml of cellular suspension ~Mac Coy cells), thcn incubated 1 hour and 24 hours at 37' C in stove. 0.2 ml of this admixture is then placed in the plates of the wells. The plates are centrifugated (1 hour at 2000 rpm) and incubated 1 hour at 37- C. The culture medium ,.,~, .~, . ... . .

-` ~L32~ 30 is then replaced with 0 2 ml of new medium containing 0.5 mg/l of cycloheximide and the plates are then incubated 48 hours at 37 C. The cellular layer is then fixed with methanol and overall couloured with a monoclonal antibody and conjugate with FITC (fluorescein isothiocyanate). Then the inclusions present in the Mac Coy cells are observed with an inversed epifluorescence microscope.
;
herefore, the toxicity of the substances to be tested was first tested, and was taken into account for s totally respecting the integrity of the host-cell.

. for Pseudominas Aeruqinosa :

- Preparation of a dense solution with two strains.

- suspension in isotonic solution of NaCl ~0.85 O in weight).
.
Checking that the suspensions include the same number of bacteria : regular techniques in gelose medium by grooved seeding (1 ~1 ansa) of the successive dilutions of the original dense solutions (geometrical ratio 10).
Incubation 18 hours at 37- C.

Preparation of the dilutions of the substances to be tested in solution in bidistilled sterile water. Range of dilution with geometrical ratio of 2 (e.g. from 2000 to 0.015 ~g/ml).

Admixturc of the Pseudominas Aeruginosa bacterial suspension (same origin as the AFNOR standards), with a constant concentration (= 4 X 107 bacteria/ml) and witll the dilution of the substances in a decreasing order (2000 to 0.015 ~g/ml).

Incubation or contact time : 11 hourl 24 hours and 48 hours in stove at 37- C.

1326~ 31 .

The tests were doubled for each dilution of substance.
- Observation of the number of survivors recorded with regard to the average number of the comparative strains cultured simultaneously with the tcsts.

- Observation after 1 hour, 29 hours and 48 hours /
for TrePonema. Gardnerella. Ducrev's Pacillas. StrePtococci and StaPhylococcus Aureus :

The methodology used is the one described by Professors F. CATALAN, P. SEDNAOUI, A. MILOVANOVIC and al., A.
FOURNIER INSTITUTE.

COHPMATIVE TEST N ~ 7:

With benzalkonium chloride alone and nonoxynol 9 alone, the following results were obtained :

Minimal inhibiting concentration S T R A r N S (MIC) Denzalkonium fluoride alone ... _ .
Gonococcus 1.15 mgtl Treponema 70 mg/l Trichomonas 1.3 mg/l Candidas Albicans 50 mg/l Chlamydia 100 mg/l Gardnerella 50 mg/l Ducrey's ~acillus 75 mg/l Streptococcus 15 mg/l Pseudomonas Aeruginosa 31.25 mg/l Staphylococcus Aureus 1.56 mg/l 1~26~ 32 _ . ~
Mlnimal inhibitiny concentrdtior S 1' R A I N S (MIC) Nonoxynol 9 alonc _ _ _ . __ _ _ __ .
Tr~ponemcl 75 mg/l E'seudomonas Aeruginosa 50 mg/l Staphylococcus Aureus 4 mg/l Streptococcus ~ 20 mg/l -TEST N 8:

The same test as precedently, conducted in presence of fluoridc anion F gave the following results :

. _ ._ Minimal inhibiting concentration S T R A I N S (MIC) _ _ __ ~en2alkonium fluoride + F
1 microgramlml .. _____ Gonococcus 0.60 mg/l Treponema 56 mg/l Trichomonas 0.9 mg/l Candidas Albicans 35 mg/l Chldmydia 85 mg/l G.ardnerella 41 mg/l Ducrey's ~acillus 62 mg/l Streptococcus 9 mg/l ~ ~ e-ld omc,llaS Ae ~ u ~J i Il~l C.d 1 a mgll ~.taphylococcus Allrcu. 1.1 m~l]
_ . __ _ _ 1 3~ 6 ~

Minimal inhibiting conccntratic,n ., S T R A I N S (MIC) ._ Nono~yl1ol 9 ~ F
1 mlcrogram/ml __ Treponcma 60 mg/l : Pseudomonas Aeruginosa 35 mg/l Staphylococcus Aureus 2.5 mgtl Streptococcus 15 mg/l ; _ ......... _ COMPMATIVE ~EST N 9:

This test was conducted with a substance including bellzalkonium chloride without activating ingredient but in presence of serous proteins. It gave the following results :
!

.. _ . . ... _ CONCENTRATIONS Minimal inhibiting S T R A I N S IN SEROUSconcentration tMIC) PROTEINS
Benzalkonium chloride alot1c Streptococcus Faecalis O 15 mg/m]
30 mg/ml 15 mg/ml 60 mg/ml 16 mg/ml 90 mg/ml 68 mg/ml __ _ .
Neisseria Gonorrhoeac O 1.5 mg/ml 30 mg/ml 1.5 mg/ml 60 mg/ml 1.5 mg/ml _.90 mg/ml 9 mg/ml This test shows the known unfavourable effect of thç serous protcins upon the efficiency of benzalkonium chloride.

.

.

1 3 2 ~

~EST N 10:

This te~t was conducted identically with test N' 9, but in pres~n~e of fluoride anion F in the composition. The fol.lowiny ` results were obtained.
,.~
., . ._ ..
.. CONCENTRATIONS Minimal inhibiting S T R ~ I N S IN SEROUS concentration (MIC) PROTEINS _ _ __ _ .~ Benzalkonium chloride + F
. 1 microgram/ml Streptococcus _ _ _ Fdccdlis 0 9 mg/ml 30 mg/ml 9' mg/ml 60 mg/ml ~ mg/ml . ~ 90 mg/ml 21 mg!ml Neisseria Gon~rrhoeae 0 0.6 mg/ml 30 mg/ml 0.6 mg/ml 60 mg/ml 0.6 mg/ml _90 mg/ml 1.2~mg/ml This test shc~ws that fluoride anion F advantageously decrcases the unfavourable effect of the serous proteins.

COMPARATIYE TEST N~

This test was conductcd on galcnical torms in vitrc- (similarly to tests N' 5 et 6), with products containing benzalkvnium chloride as active ingredien~ an(3 free of activating ingrcdient.

The following results were obtained :

~326~ 35 ._ ~
; GALENIC FORM Minimal inhibiting Concentrati.on (MIC) S 1 R A I N _ _ _ ~enzalkonium chloride alonc __ _ _ _~
Gol1ococcus ovule 23.65 mg/l tablet 15.62 mg/]
_ .................................. ~
Trichomonas ovule 11.80 mg/l tablet 15.60 mg/l __ . _ ._ .

The concentrations are those present in the liquid obtained after simu]ation, used for the test.

TEST N 12:

This test was cc~ndlicted in the s~me conditions as the comparative te.,t- N- 11 from products contail1ing 0.5 O ~in weigl1t) of fluoride anion F .

The following results were obtained :
.
GALENIC FORM Minimal inhibiting Concentration (MIC) 5 T R A I N S _ ..
8enzalkonium chloride ~ 0.5 ~ F
. __ _._ .
Gonococcus ovule 5 mg/l tablet 3 mg/l . _ .__ Trichomonas ovule 5 mg/l _ tablet 3 mg/l ~ --III) USE OF THE INVENSION IN THE FIELD OF DISINFECTION :
. _ !

This field relates to the treatment of floors, surfaces, instruments ... with contact bactericidal products.

1326~6 36 The preferred embodiments of the invention for this use are as ~:)1 Ic)ws ~, ________ . _ ~
~enzalkonium Anion F Excipiel1ts . . UTILIZATIONS Chloride ___... ... .... __._ _ . . ... _ ._ ._ _ llands purified water 0.1 3 0.25 3 or alcohol . Epidermis to make up for 100 3 . _ ._ _ . Instruments purified water to be steri].ized 1.0 3 0.50 3 to be disinfected to make up for 100 %
. . .
purified water Textiles 0.05 % 0.025 ~
: to make up for 100 3 .. _ . _ Instruments Ethanol 10 ~
: 1.0 3 0.50 3 purified water (e.g. thermometer) to make up for 100 0 _ __ . _ .__ _ . _ _ ._ Cleaning of purified water surfdces trooms, 0.1 O 0.25 ~O
floor... ) to make up for 100 3 .

The tests were conducted according to the standard AFNOR NFT
72-150, March 81, with benzalkonium chloride, then with nonoxynol 9 as active ingredlent.

The neutralizer used was as follows : 3 ~0 Tween ~0 ~V/V) and 0.3 O lecithin (M/V). Thc pH of the medium WdS 7.2.

COMPARATIVE rEsr N~ 13:

This test was col1ducted without activating in-3redient :

~ 37 .
Minimal inhibiting Concentration (MIC) S T R A I N S _ _ Benzalkonium chloride alone _ . Pseudomot1as aeruginosa CNCM A 22 31.25 mg/l Es,-herichia coli CNCM 54 127 6.57 mgll Staphylococcus Aureus Oxford origin CNCM 53 154 1.56 my/l Str~-ptc,coccus faecalis CNCM 5 855 4 mg/l Mycobacterium smegmatis CNCM 7 326 30 mg/l _ _ ~
Minimal inhibiti.ng Concel1t.ration ~MIC) S T R A I N S
Nonoxynol 9 alone Pseudomonas aeruginosa CNCM A 22 50 mg/l Escherichia coli CNCM 54 127 8 mg/l Staphylococcus AurelJs Oxford origin CNCM 53 154 4 mg/l Streptococcus faecalis . cr~ 5 855 7 mg/l Mycobacterlum ~megmatis CNCM 7 326 65 mg/l . _ rEST N~ 14:

This test is identic.1l to the previous one but in prescrl.e of fluoride anion ~~ as activ~ting ingrediel1t.

.

1326~.~c6 38 __ Minimal inhibiting Concentration (MIC) S T R A I N S .. _ _ .
Benzalkonium chloride + F
1 microgram/ml __ _ ___ _ Pseudomonas aeruginosa CNCM ~ 22 18 mg/l Escherichla coli CNCM 54 127 3 mg/l Staphylococcus Aureus Oxford origin CNCM 53 154 1.1 mg/l : Streptococcus faecalis : CNCM 5 855 3.6 mg/l Mycobacterium smegmatis CNCM 7 326 26 mg/l Minimal inhibiting Concentration ~MIC) S T R A I N S .
Nonoxynol 9 ~ F
1 microgram/ml ._ ._ .. __ . _ __ Pseudomonas aeruginosa CNCM A 22 35 mg/l : Escherichia coli CNCM 54 127 6.5 mg/l Staphylococcus Aureus Oxford origin CNCM 53 154 2~5 mg/l Streptococcus faecalis CNCM 5 855 5.5 mg/l Mycobacterium smegmatis CNCM 7 326 50 mgtl rv) USE OF THE INVENTION IN COSMETOLOGY :
. _ .. ___ __ __ .__ _____ The preferred embodiments of the inventivn in cosmetolc.gy are described hereinafter :

The following galenical ~orms may be presented in cosme~ology :
creams, milks,pommades, solutions, foaming bath, synthetic sbaps, -` 1326~
shampoos, intim~te lotions, disinfecting lotions.

~ The formula of the excipients are the same as for the . pharmaceutical preparations but the concentrations in :I benzalkonium chloride and anion F- are different. Those concentrations are prefcrably as follows for all the products 0.2 ~ benzalkonium chloride and 0.1 % fluoride anion F .
~`:
Chemical or naturally originated active ingredients may also enter into these formulae with concentrations and doses which are allowed in cosmetology.

The creams and milks may be in continuous aqucous phase (oillwater or water/oil emulsion) or pasty when warm, self diluting in water.
:, The various excipients referred to as examples correspond in a non-restrictive and indicative way to the following products :

` . Humectants : glycerol, propylene glycol, diethyleneglycol, glycol, sorbitol, polyoxyethylene glycol.

. Emulsifiers : sodium stearate, beeswax, sorbitolester, polyoxyethylene glycol ester, fatty alcohol, triethanolamine lanoline, tween, glycol stearate and polyglycols.

Stabilizers : glycol stcarate, cetylic alginate alcollol, pectin, gum, fatty esters of polyols, soluble cellulose esters.

Antioxygens : tar~aric acid, citric and ascorbic acid.

Antiseptic : boric acid, benzoic acid, parabenzoic acid, clnd their mcthylic or propylic esters, soded or not.

E'H : all these formulas are particularly efficient with pH
compris-d between 4.5 ~nd 6.5. ~or obtaining such a range, citric acid is mainly used.

Claims (125)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A composition for inhibiting or destroying at least one unicellular living creature or virus such as protozoa, microbe, bacterium, gamete, fungus which comprises at least one basic active ingredient inhibiting or destroying said unicellular living creature or virus and at least one fluorinated compound capable of emitting fluoride anion.

2. A composition according to claim 1, in which the active ingredient hinders the working of the couple enzyme substrate.

3. A composition according to claim 2, in which the fluorinated compound is a metallic derivative of fluoride.

4. A composition according to claim 2, in which the fluorinated compound is selected from sodium fluoride, calcium fluoride, potassium fluoride, aluminum fluoride, tin fluoride, ammonium fluoride and sodium monofluorophosphate.

5. A composition according to claim 1, in which fluoride anion F- concentration emitted by the fluorinated compound is inferior to the minimal inhibiting concentration (MIC) of fluoride anion F- without the basic active ingredient.

6. A composition according to claim 1, 2, 3, 4 or 5, in which the basic active ingredient concentration is inferior to the minimal inhibiting concentration (MIC) of the basic active ingredient without the fluorinated compound.

7. A composition according to claim 1, 2, 3, 4 or 5, in which the basic active ingredient itself is capable of emitting fluoride anion.

8. A composition according to claim 1, in which the fluorinated compound itself is an active ingredient inhibiting or destroying at least one unicellular living creature or virus.

9. A pharmaceutical composition which comprises at least one basic active ingredient and at least one fluorinated chemical compound capable of emitting fluoride anion F-, and which function consists in increasing the efficiency of the effective of the basic active ingredient.

10. A cosmetic composition which comprises in combination at least one basic active ingredient and at least one fluorinated chemical compound capable of emitting fluoride anion F- and which function consists in increasing the efficiency of the effect of the basic active ingredient(s).

11. A local contraceptive composition which comprises at least one chemical compound capable of emitting fluoride anion F-, as active ingredient inhibiting or destroying gametes, directly or by potentiation, and an excipient.

12. A composition according to claim 11, which is a spermicidal composition.

13. A composition according claim 11, in which the active ingredient inhibiting or destroying gametes is at least one fluorinated chemical compound capable of emitting fluoride anion F-.

14. A composition according to claim 13, in which the titer of F- in the composition is greater than 4.5 ppm, in order to obtain a spermicidal activity of 100% according to the total spermicidal test of IPPF.

15. A composition according to claim 14, in which the titer of F- in the composition is greater about 5 ppm.

16. A composition according to claim 11, in which comprises at least one other compound as basic active ingredient inhibiting or destroying gametes, and which inhibiting or destroying ability is increased with the presence of fluoride anion F-.

17. A composition according to claim 1, in which the basic active ingredient is a quaternary ammonium composition.

18. A composition according to claim 16, in which the basic active ingredient is a quaternary ammonium compound.

19. A composition according to claim 1, which comprises a surfactant, said surfactant being a basic active ingredient.

20. A composition according to claim 19, which comprises benzyl alkylbenzalkonium.

21. A composition according to claim 19, which comprises a methyltauride sodium oxysalt.

22. A composition according to claim 19, which comprises a derivative of amidoethylglycinate on fatty acids.

23. A composition according to claim 19, which comprises nonoxynol.

24. A composition according to claim 16, which comprises a surfactant, said surfactant being a basic active ingredient.

25. A composition according to claim 1, which comprises phenylmercuric nitrate or para-methanylphenylpolyoxyethylene ether or a trisodium salt of polysaccharide sulfuric ether as basic active ingredient.

26. A composition according to claim 16, which comprises phenylmercuric nitrate or para-methanylphenylpolyoxyethylene ether or a trisodium salt of polysaccharide sulfuric ether as basic active ingredient.

27. A drug, which comprises a composition according to claim 1.

28. Antiseptic and/or disinfectant which comprises a composition according to claim 1.

29. A local antiseptic product which comprises a composition according to claim 1.

30. Antiprotozal which comprises a composition according to claim 1.

31. A local antiprotozal product which comprises a composition according to claim 1.

32. Bactericide which comprises a composition according to claim 1.

33. A local bactericide which comprises a composition according to claim 1.

34. Antifungal which comprises a composition according to claim 1.

35. Local antifungal which comprises a composition according to claim 1.

36. Antibiotic which comprises a composition according to claim 1.

37. Local antibiotic product which comprises a composition according to claim 1.

38. Antiviral which comprises a composition according to claim 1.

39. Local antiviral product which comprises a composition according to claim 1.

40. Cosmetic product, which comprises a composition according to claim 1.

41. Contraceptive product which is locally applied in contact with gametes, which comprises a composition according to claim 1.

42. A contraceptive ovule, cream, gel, solution, foam, tablet, soluble waffle, tampon, vaginal suppository, which comprises a composition according to claim 1.

43. In a cosmetic product, use of a composition including at least one basic active ingredient, and at least one fluorinated chemical compound capable of emitting fluoride anion F- as activator ingredient of said basic active ingredient(s).

44. Use of a fluorinated chemical compound capable of emitting fluoride anion F- for manufacturing a substance including at least one basic active ingredient, as activator of said basic active ingredient.

45. Use of a composition according to claim 1, in the manufacture of a drug to be used as antibiotic and/or antiprotozoal and/or bactericide and/or antifungal and/or antiseptic and/or antiviral.

46. Use of a composition according to claim 1, in the manufacture of a local contraceptive for a human or animal inhibiting or destroying gametes.

47. Process of manufacture of a substance or composition inhibiting or destroying at least one unicellular living creature or virus in which at least one basic active ingredient inhibiting or destroying said unicellular living creature or virus is mixed with at least one fluorinated compound capable of emitting fluoride anion.

48. A compound for use in a local contraceptive method for a living being, which comprises ionizable fluorine.

49. A compound according to claim 48, which is a metallic derivative of fluorine.

50. A compound according to claim 48 or 49, which is selected from sodium fluoride, calcium fluoride, potassium fluoride, aluminum fluoride, tin fluoride, ammonium fluoride, and sodium monofluorophosphate.

51. A compound according to claim 48, which is an organic fluorinated compound capable of emitting fluoride anion F-, either spontaneously or after enzymic action.

52. Use of a compound comprising at least one basic active ingredient inhibiting or destroying a unicellular living creature or virus and at least one fluorinated compound capable of emitting fluoride anion in a process of inhibition or destruction of at least one unicellular living creature or virus which comprises contacting said unicellular living creature or virus with said composition.

53. The use of a compound according to claim 52, wherein said fluorinated compound is an agent hindering the working of the couple enzyme/substrate.

54. The use of a compound according to claim 52, comprising the use of a fluoride anion F- concentration emitted by the fluorinated compound which is inferior to the minimal inhibiting concentration (MIC) of fluoride anion F- without basic active ingredient.

55. The use of a compound according to claim 52, including the use of a basic active ingredient concentration which is inferior to the minimal inhibiting concentration (MIC) of this basic active ingredient without the fluorinated compound.

56. The use of a compound according to claim 52, including the use of a basic active ingredient which is itself capable of emitting fluoride anion.

57. The use of a compound according to claim 52, including the use of a fluorinated compound which is itself an active ingredient inhibiting or destroying at least one unicellular living creature or virus.

58. The use of a compound according to claim 56, including the use of a titer F- in the composition which is greater than 4.5 ppm in order to obtain a spermicidal activity of 100% according to the total spermicidal test of IPPF.

59. The use of a compound according to claim 56, including the use of a titer F- in the composition which is about 5 ppm in order to obtain a spermicidal activity of 100% according to the total spermicidal test of IPPF.

60. The use of a compound according to claim 52, including the use of a quaternary ammonium as basic active ingredient.

61. The use of a compound according to claim 52, including a surfactant which is a basic active ingredient.

62. The use of a compound according to claim 52, including the use of phenylmercuric nitrate or para-methanylphenylpolyoxyethylene ether or a trisodium salt of polysaccharide sulfuric ether as basic active ingredient.

63. Process of manufacture of a substance or composition inhibiting or destroying at least one unicellular living creature or virus in which at least one basic active ingredient inhibiting or destroying said unicellular living creature or virus is mixed with at least one fluorinated compound capable of emitting fluoride anion.

64. A process according to claim 63, in which the fluorinated compound is an agent hindering the working of the couple enzyme/substrate.

65. A process according to claim 63, in which the activating ingredient is a metallic derivative of fluorine.

66. A process according to claim 63, in which the activating ingredient is selected from sodium fluoride, calcium fluoride, potassium fluoride, aluminum fluoride, tin fluoride, ammonium fluoride, and sodium monofluorophosphate.

67. Process according to claim 63, in which the fluoride anion F- concentration emitted by the fluorinated compound is inferior to the minimal inhibiting concentration (MIC) of fluoride anion F- without the basic active ingredient.

68. A process according to claim 63, including the use of a basic active ingredient concentration that is inferior to the minimal inhibiting concentration (MIC) of the basic active ingredient without the fluorinated compound.

69. A process according to claim 63, in which there is a basic active ingredient that is itself capable of emitting a fluoride anion.

70. A process according to claim 63, in which there is used an activating ingredient that is itself an active ingredient inhibiting or destroying at least one unicellular living creature or virus.

71. A pharmaceutical composition including at least one basic active ingredient and at least one fluorinated chemical compound capable of emitting fluoride anion F- and which function consists in increasing the efficiency of the effect of the basic active ingredient(s).

72. A cosmetic composition including in combination at least one basic active ingredient and at least one fluorinated chemical compound capable of emitting fluoride anion F- and which function consists in increasing the efficiency of the effect of the basic active ingredient.

73. A local contraceptive composition, including at least one chemical compound capable of emitting fluoride anion F-, as active ingredient for inhibiting or destroying gametes, directly or by potentiation, and an excipient.

74. The composition according to claim 73, which includes a unique active ingredient for inhibiting or destroying gametes that is made of at least one fluorinated chemical compound capable of emitting fluoride anion F-.

75. The composition according to claim 74, which includes a titer of F- in the composition that is greater than 4.5 ppm, in order to obtain a spermicidal activity of 100% according to the total spermicidal test of IPPF.

76. The composition according to claim 73, which includes at least one other compound as basic active ingredient for inhibiting or destroying gametes, and which inhibiting or destroying ability is increased with the presence of fluoride anion F-.

77. The composition according to claim 71, including a quaternary ammonium as basic active ingredient.

78. The composition according to claim 71, characterized by a surfactant which is a basic active ingredient.

79. The composition according to claim 71, including phenylmercuric nitrate or para-methanylphenylpolyoxyethylene ether or a trisodium salt of polysaccharide sulfuric ether as basic active ingredient.

80. In a cosmetic product, use of a composition including at least one basic active ingredient and at least one fluorinated chemical compound capable of emitting fluoride anion F- as activator ingredient of said basic active ingredient.

81. Use of a substance of a composition manufactured by a process according to claim 63, in the manufacture of a drug to be used as antibiotic and/or antiprotozoal and/or bactericide and/or antifungal and/or antiseptic and/or antiviral.

82. Use of a substance or a composition manufactured by a process according to claim 63, in the manufacture of a local contraceptive for human or animal being, in particular inhibiting or destroying gametes.

83. Use of chemical compound including ionizable fluorine in the form of a metallic derivative of fluorine or an organic fluorinated compound in a local contraception method for human or animal beings.

84. An antibiotic composition comprising an antibiotic principle and a fluorinated compound capable of releasing fluoride anions.

85. A composition according to claim 84, wherein said antibiotic principal is selected from the group consisting of betalactamins, macrolides, polypeptidic, antibiotics, phenicolated antibiotics, rifamycins, lincosaides, streptogramines, sulfamides, aminosides, trimethoprimes, cyclins, quinolones and their derivatives and combinations thereof.

86. A composition according to claim 84, wherein said antibiotic principal is selected from the group consisting of erythromycin, neomycin, bacitracin, oxyetracyclin chlorhydrate, aureomycin chlorydrate, soframycin sulfate, qurcomycin, ampicillin, genlamicin, norfloxacin, colistin, cefalexin, penicillin, chloramphenicol, perfloxacin, minocylin, netilmicin, and vancomycin.

87. A composition according to claim 84, wherein said fluorinated compound is a metallic derivative of fluorine.

88. A composition according to claim 84, comprising from 0.35% to 4% in weight of antibiotic principal and an amount of fluorinated compound capable of releasing from 0.25% to 0.50% of fluoride anions and an excipient.

89. A composition according to claim 84, further comprising a quaternary ammonium compound.

90. An antibiotic composition comprising a fluorinated compound capable releasing fluoride anions and an antibiotic principal compound being included in acceptable amounts for general administration of said composition.

91. A composition according to claim 90, wherein said antibiotic principal selected from the group consisting of betalactamins, macrolides, polypeptidic antibiotics, phenicolated antibiotics, rifamycins, lincosanides, streptogramines, sulfamides, trimethoprime, aminoside, cylins, quinolones and their derivatives and combinations thereof.

92. A composition according to claim 1, wherein said fluorinated compound is capable of releasing 0.025% to 0.50%
by weight of fluoride anions.

93. A composition according to claim 19, which comprises 0.05% to 1% by weight of surfactant as active ingredient.

94. A composition according to claim 1, which is constituted of a quaternary ammonium compound, a metallic derivative of fluorine and a suitable excipient.

95. A composition according to claim 94, wherein said metallic derivative of fluorine is sodium fluoride.

96. A composition according to claim 94, wherein said quaternary ammonium compound is Benzalkonium chloride.

97. A composition according to claim 1, which comprises 0.05% to 1% by weight of a surfactant and 0.025% to 0.5% by weight of anti-enzymatic fluoride anions.

98. A composition according to claim 97, which is constituted of 0.05% to 1% by weight of Benzalkonium chloride, a fluorinated compound in such an amount as to release 0.025% to 0.5% by weight of anti-enzymatic fluoride anions, and an excipient.

99. Use of at least one active principal, which inhibits or destroys at least one unicellular living being or virus, and of a fluorinated compound capable of emitting fluoride anion in proportions suitable for inhibiting or destroying at least one enzyme associated with the said unicellular living being or virus to obtain a product or a medicament for inhibiting or destroying the unicellular living being or virus, with the exception of the case of the association of benzoic acid, phenol and an alkaline fluoride in aqueous solution or hydroalcoholic solution, to obtain a product for inhibiting or destroying the herpes virus.

100. Use according to claim 99, in which the activating principle is a fluorine compound emitting ionic fluorine.

101. Use according to claim 100, in which the fluorine compound is a metal derivative of fluorine.

102. Use according to claim 101, in which fluorine compound is selected from the group sodium fluoride, calcium fluoride, potassium fluoride, aluminium fluoride, tin fluoride, ammonium fluoride and sodium monofluorophosphate.

103. use according to claim 99, in which an active principal is a surfactant surface-active compound.

104. Use according to claim 103, in which the active principal is cationic.

105. Use according to claim 104, in which the active principal is a quarternary ammonium.

106. Use according to claim 103, in which the active principal is benzalkonium chloride.

107. Use according to claim 103, in which the active principal is an anionic surfactant surface-active compound.

108. Use according to claim 103, in which the active principal is an amphoteric surfactant surface-active compound.

109. Use according to claim 103, in which the active principal is a non-ionic surfactant surface-active compound.

110. Use according to any one of claims 103 to 109, in which the active principal is selected from the group consisting of sodium salt oxide methyltauride, a derivative of aminoethylglycinate of fatty acid, a nonoxynol, phenylmercury nitrate, paramenthanylphenylpolyoxyethylene ether, and a trisodium salt of polysaccharide sulphuric ether.

111. Use according to claim 99, to obtain a product or a medicament for inhibiting or destroying a protozoan, or a microbe, or a bacterium, or a gamete, or a fungus, or a virus.

112. Use according to claim 99, to obtain a product or a medicament for inhibiting or destroying at least one unicellular living being or a virus selected from the group consisting of gametes, Gram-positive cocci, Gram-negative cocci, Gram-positive bacilli, Gram-negative bacilli, bacilli resistant to acid alcohols, bacteria, flagellated protozoa, yeasts, viruses and retroviruses.

113. Use according to claim 99, of at least one active principal which inhibits destroys gametes and of a fluorinated compound capable of emitting fluoride anion in proportions suitable for inhibiting or destroying at least one enzyme associated with the said gamete to obtain a local contraceptive product.

114. Use according to claim 113, of benzalkonium chloride and of a fluorine compound emitting ionic fluorine, in proportions suitable for obtaining a product in the form of a pessary, cream, lotion, unguent, ointment, gel or soluble film containing 1.20% by weight of benzalkonium chloride and 0.50% by weight of the anion F-, or a product in the form of a tablet containing 25 mg per tablet of benzalkonium chloride and 10 mg per tablet of the anion F-, or a product in the form of a synthetic soap containing 2% by weight of benzalkonium chloride and 1% by weight of the anion F-, or a product in the form of a solution containing 0.50%
by weight of benzalkonium chloride and 0.25% by weight of the anion F-.

115. Use according to claim 99, of at least one active principal which inhibits or destroys at least one unicellular living being responsible for sexually transmitted diseases and a fluorinated compound capable of emitting fluoride anion in proportions suitable for inhibiting or destroying at least one enzyme associated with the said unicellular living being to obtain a medicament intended to combat sexually transmitted diseases.

116. Use according to claim 115, of benzalkonium chloride and a fluorine compound emitting ionic fluorine in proportions suitable for obtaining a product in the form of a pessary, cream, lotion, unguent, ointment, gel or soluble film, containing 1.20% by weight of benzalkonium chloride and 0.50% by weight of the anion F-, or a product in the form of a tablet containing 25 mg per tablet of benzalkonium chloride and 10 mg per tablet of the anion F-, or a product in the form on a synthetic soap containing 2% by weight of benzalkonium chloride and 1% by weight of the anion F-, or a product in the form of a solution containing 0.50% by weight of benzalkonium chloride and 0.25% by weight of the anion F-.

117. Use according to claim 115, in which an active principal is a fluorine compound capable of emitting ionic fluorine.

118. Use according to claim 99, of at least one active principal having an antibiotic action towards at least one unicellular living being and of fluorinated compound capable of emitting fluoride anion in proportions suitable for inhibiting or destroying at least one enzyme associated with the said unicellular living being to obtain medicament to combat by antibiotic therapy the diseases for which the unicellular living being is responsible.

119. Use according to claim 118, of benzalkonium chloride or erythromycin base or neomycin base or bacitracin or oxytetracycline hydrochloride or aureomycin hydrochloride or soframycin sulphate or aureomycin, or oxytetracycline and a fluorine compound capable of emitting ionic fluorine to obtain a medicament in the form of a cream, or lotion, or unguent or ointment containing 1.20% by weight of benzalkonium chloride and 0.50% by weight of the anion F-, or a medicament in the form of a synthetic soap containing 2% by weight of benzalkonium chloride and 1% by weight of the anion F-, or a medicament in the form of a solution containing 0.05% by weight of benzalkonium chloride and 0.25% by of the anion F-, or a medicament in the form of a solution or gel containing 4% by weight of erthromycin base and 0.5% by weight of anion F-, a medicament in the form of an ointment containing 0.35% by weight of neomycin base and 0.50% by weight of the anion F-, or 50,000 international units % and 0.50% of the anion F-, or 3% by weight of oxytetracycline hydrochloride and 0.50% by weight of the anion F-, or 3% by weight of aureomycin hydrochloride and 0.50% by weight of the anion F-, or a medicament in the form of a cream containing 2.5% by weight of soframycin sulphate and 0.50% by weight of the anion F-, or a medicament in the form of an ophthalmic ointment containing 1% by weight of aureomycin and 0.50% by weight of the anion F- or 0.50% by weight of oxytetracycline and 0.25% by weight of the anion F, or a medicament in the form of a nasal solution containing 1.25% by weight of soframycin sulphate and 0.50% by weight of the anion F-.

120. Use according to claim 118, of benzalkonium chloride or erythromycin base of neomycin base or bacitracin or oxytetracycline hydrochloride or aureomycin hydrochloride or soframycin sulphate or aureomycin, or oxytetracycline and a fluorine compound capable of emitting ionic fluorine to obtain a medicament in the form of a solution or a gel containing 4% by weight of erythromycin base, 0.5% by weight of the anion F- and 0.10% of benzalkonium chloride, or a medicament in the form of an ointment containing 0.35% by weight of neomycin base, 0.50% of the anion F-, and 0.10% of benzalkonium chloride, or 50,000 international units %, 0.50%
of the anion F- and 0.10% of benzalkonium chloride, or 3% by weight of oxytetracycline hydrochloride, 0.50% by weight of the anion F- and 0.10% of benzalkonium chloride, or 3% by weight of aureomycin hydrochloride, 0.50% by weight of the anion F- and 0.10% of benzalkonium chloride, or a medicament in the form of a cream containing 2.5% by weight of soframycin sulphate, 0.50% by weight of the anion F- and 0.10% of benzalkonium chloride or a medicament in the form of an ophthalmic ointment containing 1% by weight of aureomycin, 0.50% by weight of the anion F- and 0.10% of benzalkonium chloride or 0.50% by weight of oxytetracycline, 0.25% by weight of the anion F- and 0.10% of benzalkonium chloride, or a medicament in the form of a nasal solution containing 1.25%
by weight of soframycin sulphate, 0.50% by weight of the anion F- and 0.10% of benzalkonium chloride.

121. Use according to claim 99, of at least one active principal which inhibits or destroys at least one fungus and a fluorinated compound capable of emitting fluoride anion in proportions suitable for inhibiting or destroying at least one enzyme associated with said fungus to obtain an antifungal product.

122. Use of at least one active principal which inhibits or destroys at least one protozoan and of a fluorinated compound capable of emitting fluoride anion in proportions suitable for inhibiting or destroying at least one enzyme associated with the said protozoan to obtain an anti-protozoic product.

123. Use of at least one active principal which inhibits or destroys at least one bacterium and of a fluorinated compound emitting fluoride anion in proportions suitable for inhibiting or destroying at least one enzyme associated with the said bacterium to obtain a bactericidal medicament or product.

124. Use according to claim 123, of benzalkonium chloride and of fluorine compound emitting ionic fluorine to obtain a bactericidal contact product containing 0.1% of benzalkonium chloride and 0.25% of the anion F-, or 1% of benzalkonium chloride and 0.50% of the anion F-, or 0.05% of benzalkonium chloride and 0.025% of the anion F-.

125. Use according to claim 99, of at least one active principal which inhibits or destroys at least one virus or retrovirus and of a fluorinated compound emitting fluoride anion in proportions suitable for inhibiting or destroying at least one enzyme associated with the said virus or retrovirus to obtain an antiviral medicament or product.