FI89675B - ICKE-PHARMACEUTICAL COMPOSITION OF A COMPOSITION OF FLUORFOERING - Google Patents

Abstract

Pharmaceutical or cosmetic substance or composition inhibiting or destroying at least one monocellular living being and/or at least one virus, medicament or product including such composition, process for producing such composition, chemical compound entering in such composition, and process for the inhibition or destruction of at least one unicellular living being and/or at least one virus. The inhibiting or destroying substance, according to the invention, is characterized in that it comprises at least one basic active principle inhibiting or destroying said unicellular living being and a principle for inhibiting or destroying at least one enzyme associated with said living being, forming an activator - particularly acting by synergy - of the basic active principle.

Description

χ 89675

The invention relates to a non-medicinal composition for inhibiting or destroying unicellular organisms, i.e. living organisms such as protozoa, microbes, bacteria, gametes, fungi or the like, and viruses. Thus, the technical fields to which the invention is particularly directed 10 are local contraception, cosmetics and disinfection.

In the following, "inhibition" of a unicellular living organism or virus means either to prevent its proliferation or to render it incapable of performing some of its normal functions. The term "destruction" means the killing of these unicellular living organisms or viruses.

Biological, pharmaceutical or cosmetic agents, which are useful in a broader context, such as disinfection or the like, which inhibit or destroy unicellular organisms are already known in the art.

In particular, U.S. Patent Nos. 4,339,441 and 4,359,475 disclose spermicidal preparations.

Numerous chemical compounds are also known in the art that can be used in methods useful for living beings for the topical prevention of pregnancy. In particular: it is known that interfacial stress-reducing surfactants (e.g. quaternary ammonium ions, nonoxynols, amidoethyl; glycinate derivatives of fatty acids, sodium oxide salt of methyl tauride, etc.) as well as some other compounds such as phenyl nitrate, paramentanylphenyl polyoxyethylene ether or the 2 39675 trisodium salt of sulfur ether derived from a polysaccharide have inhibitory or destructive effects on unicellular living organisms, in particular spermicidal activity.

5 Agents which act mechanically on sperm cells, for example by immobilizing them, are also known in the art. U.S. Patent No. 4,368,186 describes such effects, in particular the combination of a "poloxamer" with sperm inhibitors to control the gelation and solubility of the products, which mechanically improves the efficacy of these inhibitors due to an additional effect or synergistic effect.

Topical anti-fertilization preparations are also known in the art, in particular spermicidally active preparations containing such compounds, which can be used topically to inhibit the fertility of gametes (gametes), in particular human and animal sperm cells.

These known preparations contain an inhibitory chemical compound in a concentration higher than the lowest inhibitory concentration, abbreviated as PIP, in solution or suspended in a pharmaceutically acceptable excipient, depending on the galenic form used. It is known that for the killing of all sperm containing 0.2 ml of sperm in less than 5 seconds (a condition set for a full spermicidal test according to the standards of the International Planned Parenthood Federation), the concentration of spermicidally active ingredient per ml the pharmaceutical preparation must be greater than or equal to the lowest inhibitory concentration of this active ingredient, i.e. PIP. The chemical combination of PTP depends on this compound, but also on the conditions in which it is used, i.e. the galenic form containing the preparation.

3 e 9675

More generally, pharmaceutical or cosmetic preparations containing at least one active basic ingredient which inhibit or destroy at least one unicellular living organism, as well as medicaments or cosmetic products containing such preparations, are known in the art.

Numerous such active substances are known in the field of antiseptics and disinfection: halogens (chlorinated or iodinated derivatives, etc.), aldehydes, alcohols, phenols, acids, metals (silver, copper, mercury, zinc salts, etc.), amidines, biguanides , diphenylurea, oxidizing agents (hydrogen peroxide, potassium permanganate, etc.), coloring agents, interfacial tension reducing agents and wetting agents (cationic, anionic, amphoteric or organic).

Also known in the art are antiseptic and / or disinfectant and / or protozoan and / or antifungal and / or antibiotic and / or antiviral products containing such inhibitory or destructive agents, as well as methods for preparing these agents or preparations.

Known substances or preparations are generally satisfactory, but there are some problems with their actual use. 25 These problems are essentially as follows:

First, it is generally desirable to achieve a fully inhibitory or destructive efficacy of unicellular living organisms or viruses, i.e., it is desirable that under practical conditions of use, the degree of inhibition or destruction be 100%.

However, this is not always the case if strict precautions are not followed or if the dosage of the active ingredient has to be limited (for example in the case of cosmetic products).

Furthermore, it is generally desirable that the preparation be active against one or more specific unicellular living organisms or viruses, for example germ cells or pathogenic organisms, without causing undesirable short- and / or long-term side effects (including activity against other unicellular living organisms). against irritation, environmental damage, etc.). However, in practice 5, it has been found that the doses necessary to solve the above-mentioned problem cause long-term side effects (usually associated with regular use) as well as even short-term side effects (from time to time or at the beginning of use). In medicine, certain threshold values and certain active ingredients have been found to have some teratogenic and / or carcinogenic effects. When used for disinfection, some adverse effects on the materials to be disinfected may be observed.

15

It is an object of the invention to improve the inhibitory or destructive capacity of a particular mixture containing an inhibitory or destructive active ingredient at a certain limited concentration without increasing that concentration. Another object of the invention is to reduce the concentrations of these basic active ingredients without thereby reducing the inhibitory or destructive capacity of the mixture, in order to better prevent side effects and to better control the selectivity for various unicellular living organisms and viruses.

It is a particular object of the invention to provide a new cosmetic product, more particularly a topical anti-fertilization product and a product containing such a product, which can be used either periodically if necessary or regularly and continuously for long periods without the risk of side effects such as teratogenic or carcinogenic effects, and whose efficacy is complete, i.e. at which the probability of not achieving the desired effect is statistically zero or insignificant, and all this when the product is used under very normal conditions (i.e. without precautions).

8 9 6 75 5 In addition, it is an object of the invention to provide a topical, contraceptive product which is easy to use and which is completely effective, i.e. which gives results similar to oral contraceptives, but without the associated disadvantages. .

Accordingly, the invention relates to a non-medicated composition comprising an effective amount of a surfactant suitable for inhibiting or destroying a unicellular organism or virus and an antienzymatic amount of a fluorine compound capable of releasing fluorine ions and suitable for inhibiting or destroying a unicellular organism. or a viral enzyme having a releasable fluorine-15 ion content of 0.025 to 0.5% by weight and used as an anti-fertilizer, a disinfectant or a protozoan or in a cosmetic product.

The fluorine compound, i.e. the fluorinated compound, is an activator of a surfactant which preferably has a synergistic effect. This activator or activating compound inhibits the activity of the enzyme-substrate pair.

However, according to the invention, it has surprisingly been found that such an activator can be formed from a fluorinated compound either spontaneously or by the enzyme-releasing fluoride anion F. "It has also been found that in some cases the surfactant itself is capable of releasing the activating compound, and / or or that the activating compound itself is an active ingredient that inhibits or destroys at least one unicellular living organism or virus.

More specifically, within the scope of the invention, it has been found that such a fluorinated compound is itself capable of inhibiting or destroying unicellular living organisms and viruses and that such a fluorinated compound acts synergistically on the active ingredients present.

A cosmetic product is especially a topically applied cosmetic product such as synthetic soap or milk.

The contraceptive agent applied topically to the gametes, especially the ovum, is preferably an ointment, gel, solution, foam, tablet, soluble product, tampon, or vaginal suppository.

As used herein, the term "topical" and its various grammatical forms refer to the use of a product in a predetermined location to be treated, such as the vagina or other anatomical parts, so that the effect is directed to unicellular organisms in contact with the product in the vicinity of that location. organisms or viruses, and this is in contrast to 20 general routes of administration (for example, oral or parenteral administration).

The mixture, substance or product of the invention may be used topically or administered in general ways. For example, the spermicide of the invention may be applied topically. In addition, the agents of the invention are preferably administered in general ways when it is desired to overcome the resistance of pathogenic, unicellular living organisms to conventional therapies.

30

According to the invention, an activating fluorine compound which inhibits or destroys at least one enzyme associated with said unicellular living organism or virus induces considerable sensitization of said unicellular living organism or virus to extracurricular attacks, in particular by inhibiting or destroying said active a pair of 7 B 9 6 75 van of enzyme and substrate. It is certainly known that each unicellular living organism or virus comprises a vital enzyme system. In addition, unicellular living organisms or viruses may, under certain conditions (e.g., when resistant to an antibiotic), produce certain specific enzymes that destroy the attacking agent (e.g., lactamases that destroy penicillins), which are called "protective enzymes." The invention is based on the inhibition of the activity of these enzymes, in which case the unicellular living organism is exposed to optimal conditions for the action of the active ingredients which act against it. This provides a number of advantages over products previously known in the art, such as the achievement of the above objectives and the ability to selectively affect a particular unicellular living organism or a particular class of unicellular living organisms by targeting a particular enzyme or class of enzyme. In the case of viruses, the invention seeks to inhibit enzymes necessary for their formation and / or proliferation. In the following, the term "related" or "enzymes present" refers to vital and / or protective enzymes of unicellular living organisms and / or viruses.

In the context of the invention, it has been found that fluorine F * in the ionized state acts as an activating ingredient particularly effectively and advantageously on the enzymes present in negligible and conventional concentrations. In addition, ionized fluorine F "is a very common, economical, and relatively easy-to-use substance. Its handling and use, as well as the side effects it may cause, can be well controlled depending on the doses used.

The invention can be used in two main ways: in either cosmetic or contraceptive applications (illustrated in the following examples by spermicides), or in the most common applications of 89675 s such as agriculture, disinfection (following example) or other applications.

The function of the activating fluorine compound comprises blocking the function of the enzyme system associated with said living organisms or viruses. In this way, it was found within the scope of the invention that such an activating compound inhibits the action of a pair of enzyme and substrate. For example, the fluorine compound may be a metal derivative of fluorine which releases fluoride anions F '. Some very good results have been obtained with sodium fluoride, calcium fluoride, potassium fluoride, aluminum fluoride, tin fluoride, ammonium fluoride and sodium monofluorophosphate or the like. Within the scope of the invention, for example, the following unicellular living organisms or viruses can be handled: gametes (sperm or ova) - gram-positive cocci such as Staphylococci and Streptococci - gram-negative cocci such as Gonococci - gram-positive bacilli - gram-negative bacilli such as colibacillus or Escherichia coli bacilli - acid and alcohol resistant bacilli such as mycobacteria-25, e.g. Mycobacterium smegmatis - spiral bacteria such as spirochete, e.g. Treponema - various other bacteria e.g. bacteria - squamous protozoa such as Trichomonas 30 - various yeasts such as Candida albicans - viruses or retroviruses such as HIV (human immunodeficiency virus) or Herpes virus.

For example, the following enzymes associated with at least one such unicellular living organism or virus may be treated within the scope of the invention: 9 ^ 5675

table 1

Enzyme_ Substrate

Alkaline phosphatase 2-naphthyl phosphate 5 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 Intermediate arylamidase L-valyl-2-naphthylamide Cystine arylamidase L-cystyl-2-naphthylamide

Trypsin N-benzoyl-DL-arginine-2-naphthylamide alpha-chymotrypsin N-glutaryl-phenylalanine-2-naphthylamide Acid phosphatase 2-naphthyl phosphate

Naphthol-AS-B1-Naphthol-AS-B1-phosphate phosphohydrolase alpha-galactosidase 6-Br-2-naphthyl-alpha-D-galactopyranoside beta-galactosidase 2-naphthyl beta-D-galactopyranoside beta-glucuronidase Naphthol-AS-B1-beta-D-glucuronide alpha-glucosidase 2-naphthyl-alpha-D-glucopyranoside beta-glucosidase 6-Br-2-naphthyl-beta-D-glucopyranoside N-acetyl-beta-glucosidase 1-Naphthyl-N-acetyl-beta-D-glucosaminidase amide alpha-mannosidase 6-Br-2-naphthyl-alpha-D-mannopyranoside alpha-fucosidase 2-naphthyl-alpha-L-fucopyranoside.

The surfactant used in the composition according to the invention is, for example, a cationic or anionic or amphoteric or non-ionic surfactant which reduces the stress between the interfaces, preferably quaternary ammonium. An example of a cationic surfactant is benzalkonium chloride or other alkylbenzalkonium. An example of an anionic surfactant 10 B 9675 is the oxy salt of methylturidine disodium. An amidoethylglycinate derivative of fatty acids is an example of an amphoteric surfactant. Nonoxynol is an example of a nonionic surfactant compound. This surfactant may also be preferably phenylmercuric nitrate or ether of paramentanylphenyl polyoxyethylene or the trisodium salt of the polysaccharide sulfur ether or the like (halogen, alcohol, phenol, acid, metal, amidine, biguanide, di-10). phenylurea, oxidizing agent, coloring agent, etc.).

It has been found in numerous tested applications that, in general, the activating fluorine compound itself also has direct activity against said unicellular living organism or virus. Thus, it has surprisingly been found that the combination of an activating fluorine compound and a surfactant acting as an active ingredient has a synergistic effect in that the results obtained not only correspond to the sum of the expected results in the presence of the active ingredient alone and the activating fluorine alone.

The efficacy of such active ingredients or activators can be measured by the lowest inhibitory concentration, abbreviated PIP, which is the concentration of active ingredient that induces inhibition or death of all unicellular living organisms or viruses over time.

30

The concentration of fluoride anion F * released from the activating fluorinated compound in the mixture according to the invention is preferably lower than the minimum inhibitory concentration (PIP) of fluoride anion F 'without active ingredient.

35

Likewise, the concentration of the active ingredient in the composition according to the invention may be lower than the minimum inhibitory concentration (PIP) of this active ingredient without the activating fluorine compound. Surprisingly, even in this case, the overall effectiveness of the mixture according to the invention is at least equal to either of the substances which contain only fluoride anions F "at a concentration equal to or greater than the lowest inhibitory concentration or which contain only the active ingredient at a concentration equal to or greater than the lowest inhibitory concentration.

It is further possible that the active ingredient itself is capable of releasing the fluoride anion F '. The composition according to the invention may contain several active ingredients which may act in the same or different ways and / or several activating compounds which act on at least one enzyme associated with either one or more basic ingredients.

The mixture according to the invention can be used in a number of ways to obtain products, and can be applied topically or administered systemically, depending on the use of said product.

Preferred uses of the compositions according to the invention include the control of certain non-pathogenic organisms, such as gametes, for example sperm, in the prevention of fertilization, in particular by resorting to local contraception.

The composition of the invention may also be advantageously used in cosmetic products in dosages and concentrations which do not allow the product to be classified as a pharmaceutical product.

The mixture according to the invention can also be used, for example, in agricultural, fungicidal, anti-protozoal and other similar products or also in products for surface disinfection.

12 39675

A preferred embodiment of the invention consists of products for use in the genitals of male and / or female mammals which act as spermicides.

5

Benzalkonium chloride and nonoxynol-9 are preferably used as the active ingredient, i.e. as a surfactant. As the activating fluorine compound, a metal derivative of fluorine, for example sodium fluoride, is preferably used.

All known galenic forms are useful, and include, in particular, ovule, ointment, solution, foam, tablet, soluble tablet, tampon, vaginal suppository, and the like.

The proportions in which the surfactant and the fluorinating activator are used depend on the galenic form, since only the actual in vivo induced concentrations are important for the efficacy of the product.

These proportions should vary between the lowest inhibitory concentration PIP and the highest side effect inducing concentrations. When applied topically, it should be possible to avoid hypersensitivity (irritation) of the treated parts. Toxic concentrations should be avoided when administering the product in general.

Thus, the content of benzalkonium chloride in vivo is preferably 1.2% by weight, and the content of fluoride anion F 'in vivo is preferably 0.5% by weight.

Several preferred embodiments of the invention in a number of tested uses are described below by showing experiments with a number of unicellular living organisms.

35 13

8967S

I) Application of the invention to the local prevention of fertilization

The invention preferably provides a spermicidal product which is applied topically to contact sperm, thereby inhibiting or killing sperm.

The spermicidal product of the invention may be in a variety of galenic forms, such as tablets, ovules, solutions, ointments, gels, soluble tablets, tampons, vaginal suppositories, which are inserted into the vagina before sexual intercourse to prevent fertilization by inhibiting or killing sperm before with ova.

The product according to the invention comprises a preparation containing as active ingredient at least one chemical compound according to the invention, directly or after activation from a spermicidal compound. This compound, in turn, contains ionizable fluorine, i.e. it is capable of releasing the fluoride anion F *.

The chemical compound of the invention is capable of releasing the fluoride anion F 'when dissolved, especially in its aqueous solution. It consists, for example, of a fluorine metal derivative such as sodium fluoride, calcium fluoride, potassium fluoride, aluminum fluoride, tin fluoride, ammonium fluoride, sodium monofluorophosphate, etc., or an organic fluorinated compound such as a fluorinated amine.

To measure the spermicidal activity of a chemical compound, a test for complete spermicidal activity according to IPPF standards can be used. The aim of these 35 experiments is to determine the minimum inhibitory concentration of the chemical compound PIP (expressed as a percentage by weight) in one milliliter of solution, which causes the death of all sperm present in less than 5 seconds in 0.2 millimeters to 89675 in 14 liters of semen. The test shall be carried out on at least six samples of semen obtained from different donors, in accordance with the following minimum requirements laid down by the IPPF: 5 - age of the sample: two hours; - density / mm3: 50 million sperm; - mobility: 50% of the sperm should move forward rapidly when the fresh sample is examined at a temperature of 35 to 37 ° C; - viscosity: the semen must be sufficiently liquefied, free of filaments and homogeneous when assessed with the naked eye; - the sample must be taken in a sterile glass tube which is hermetically sealed and stored at 37 ° C.

Within the scope of the invention, it was found that under these conditions the spermicidal activity of the fluoride anion F 'is 100% according to the IPPF test when present at a concentration of 5 ppm (i.e. 5 mg / l).

In addition, it was found within the scope of the invention that, in addition to its direct spermicidal activity, fluoride anion F "has spermicidal activity due to its ability to activate known spermicidal compounds. Therefore, the preparation of the invention consists of at least one active spermicidal component an active compound such as a cationic anionic, amphoteric or non-ionic surfactant which reduces the tension between the interfaces, for example the trisodium salt of paramentanyl-phenyl polyoxyethylene ether or polysaccharide sulfur ether or the like, and on the other hand at least one compound of the invention which is capable of releasing the fluoride anion F ", and finally from the filler as well as from a number of common additives (such as antioxidant, etc.).

89675 15

The concentration of the active ingredient in the preparation according to the invention may be lower than the PIP of this active ingredient without fluoride ions, but the preparation is 100% inhibitory, i.e. it fulfills the complete spermicidity according to the IPPF-5 test. The preparation according to the invention may contain a mixture of several active gametes. inhibitory constituents and / or a mixture of several different fluorinated chemical compounds.

10

The following percentages are based on weight.

Preferred embodiments of the invention for local prevention of fertilization are as follows:

Ovules benzalkonium chloride 1.20% F'-anion (eg sodium fluoride) 0.50% 20 Fillers: semi-synthetic glycerides or cocoa butter, or gelatin or glycerin and pure water, antioxidants, antiseptics.

25 Creams and milks Benzalkonium chloride 1.20% F "anion (eg sodium fluoride) 0.50% Fillers: distilled or pure water, wetting agents, emulsifiers, stabilizers, antioxidants, antiseptics used in varying proportions depending on the desired viscosity and pH).

35 Ointments and fats benzalkonium chloride 1.20% F'-anion (eg sodium fluoride) 0.50% 89675 16 Excipients: distilled or purified water, emulsifier, excipients suitable for fatty preparations (petrolatum, lanolin, lanovaseline, stearovaseline), stabilizers antioxidants, antiseptics 5 (used in varying proportions depending on the desired viscosity and pH).

Gel benzalkonium chloride 1.20% 10 F'-anion (eg sodium fluoride) 0.50% Fillers: cellulose-soluble derivatives compatible with cationic surfactants, distilled or purified water, glycerin, sorbitol, antioxidants, antiseptics (used in varying proportions depending on the desired viscosity and pH).

Soluble tablet 20 benzalkonium chloride 1.20% F'-anion (eg sodium fluoride) 0.50% Excipients: polyvinyl alcohol, glycerin, sorbitol, propylene glycol, distilled or purified water, antioxidants.

Tablets benzalkonium chloride 25 mg / tablet F'-anion (eg sodium fluoride) 10 mg / tablet 30 Excipients: lactose, magnesium stearate, cellulose, starch, citric acid, sodium bicarbonate.

Synthetic soaps 35 benzalkonium chloride 2% F'-anion (eg sodium fluoride) 1% 17 «9675 Fillers: foaming and wetting products compatible with ammonia (eg amphoteric surfactants such as betaine or aminobetaine), plasticizers, plasticizers antioxidants, anis-5 antiseptics.

Solutions benzalkonium chloride 0.50% F'-anion (eg sodium fluoride) 0.25% 10 Excipients: distilled or purified water, ethanol, antioxidants, glycerin, sorbitol, antiseptics (used in varying proportions depending on the desired pH) .

15

Comparative test no

The PIP of various known spermicidal compounds was determined by the IPPF assay. The following results were obtained with 1 milliliter of the preparation, which was reacted with 0.2 ml of sperm. In this way, sperm samples obtained from six different donors were used to determine the lowest concentration of spermicidal compounds that induced the death of all sperm in five seconds.

25 Spermicidal compound_PIP (% by weight) p-mentanylphenyl polyoxyethylene ether 0.006 trisodium salt from polysaccharide sulfur ether 0.007 30 anionic surfactant (methyl tauride sodium oxide salt) 1 cationic surfactant (benzalkonium chloride) 0.006 surfactant 0.006 (nonoxynol-9) 0.006 amphoteric surfactant (amidoethylglycinate derivative of fatty acids) 0.001 18 «9675

Koe no 2

The same IPPF test for complete spermicidity was carried out on 1 ml of a preparation already containing 0.0001% by weight of fluoride anions F 'and reacted with sperm used in 0.2 ml. In this way, samples from six different donors were used to determine the lowest concentration of spermicidal compounds that caused the death of all sperm in 5 seconds.

10

Spermicidal compound_PIP (% by weight) p-mentanylphenyl polyoxyethylene ether 0.003 trisodium salt of sulfur polysaccharide 15 0.0025 anionic surfactant (methyl tauride sodium salt) 0.50 cationic surfactant 20 (benzalkonium chloride) 0.00 ionic surfactant (nonoxynol-9) 0.003 amphoteric surfactant (amidoethylglycine 25 derivative of fatty acids) 0.0005

The results show that the inhibitory activity of the known spermicidal ingredients is significantly improved when ionizable fluorine is added to the preparation. Therefore, the preparation according to the invention may contain very little spermicidal active ingredient, in particular in a concentration lower than the lowest inhibitory concentration of this active ingredient without F'-ion.

In addition, the concentration of the F "ion used together with the active ingredient can also be very low, in particular lower than the minimum inhibitory concentration of the fluoride anion F '.

89675 19

For example, it was found within the scope of the invention that although the spermicidal activity of a solution containing 0.003% benzalkonium chloride and a solution containing 0.0001% fluoride anion F 'was not 100% according to IPPF Test 5, a solution containing both 0.003 % benzalkonium chloride and 0.001% fluoride anions F ', satisfy the IPPF test. Thus, a synergistic effect can be observed.

Experiment No. 3 In this experiment, an experiment similar to Experiments No. 1 and No. 2 above is performed, but in the presence of sodium borate to form a complex from the F'-ion. The spermicidal action of the F'-ion is then completely lost, indicating that only the F'-ion activates or is a prerequisite for the spermicidal action.

Experiment No. 4

Various perfluoro-20 benzalkonium chlorides were used as basic spermicidal compounds under the same conditions described above in Experiments Nos. 1 to 3. In this case, it was found that the spermicidal activity of perfluorinated benzalkonium chlorides is similar to that of benzalkonium chloride alone. In addition, under the conditions of Experiment No. 3, i.e., .25 in the presence of sodium borate, the activity of these compounds remains unchanged, indicating that the fluorine attached to the benzene core was not ionized.

Experiment No. 2 was similarly performed with perfluorinated benzalkonium chloride mixed with another F "ion-releasing chemical compound. Activation of the spermicidal effect by perfluorinated benzalkonium chloride was also observed. In this same experiment, performed in the presence of sodium borate ) induced spermicidal activity similar to that of perfluorinated benzalkonium chloride.

89675 20 These two experiments Nos. 3 and 4 show that the induction of the activity of the active base component takes place only in the presence of the fluoride anion F '.

To prepare the spermicidal product according to the invention, a solution containing fluoride anions F 'and optionally also the active ingredient in a certain concentration is produced, and this solution is combined with excipients corresponding to the galenic form to be prepared. In the case of tablets, the active ingredient and the chemical compound releasing fluoride ions F 'are combined with the excipient as such.

Comparative Experiment No. 5 This in vitro experiment was performed with galenic products containing benzalkonium chloride as the active ingredient. The experiment determined the PIP of this benzalkonium chloride in vitro under conditions mimicking the state (extraction, dissolution, etc.).

This experiment without activating ingredient gave the following results:

Galenic form of benzalkonium chloride _PIP. weight% _ 25 Ovule 0.0063

Cream 0.0083

Tampons 0.0075

Tablet 0.0095

Soluble tablet 0.0080 30 Gel 0.0080

Percentages refer to the weight percentages of benzalkonium chloride in the solution used in the in vitro spermicidal IPPF assay, obtained after simulating in vivo conditions. These proportions were determined by titration of a sample taken from this solution.

89675 21

Experiment No. 6 The same conditions as in Comparative Experiment No. 5 were used in this experiment, however, each galenic form initially containing 0.45% by weight of fluoride anions F ".

5 The following results were obtained:

Galenic form of benzalkonium chloride _PIP. weight-%_

Ovule 0.0023 10 Cream 0.0030

Tampons 0.0025

Tablets 0.0025

Soluble tablet 0.0017

Gel 0.0033 15 II) Use of the invention for disinfection

Disinfection involves the treatment of floors, surfaces, instruments, 20, etc. with bactericidal products.

Preferred embodiments of the invention for this purpose are:

Benzalko- F'- Applications nium chloride_anion Fillers „85675 22 Hands 0.1% 0.25% purified water 5 Epidermis or alcohol already added 100% missing part

Sterilizable 1.0% 0.50% purified water, 10 or added to disinfect 100% missing instruments part

Textiles 0.05% 0.025% purified water to which is added 100% of the missing portion

Instruments 1.0% 0.50% 10% ethanol, 20 (eg heat-treated water, meters) to be added 100% missing part 25 Surface clean 0.1% 0.25% purified water, distillation to be added (rooms , lat- 100% missing thiats, etc.) Part 30 These experiments were performed according to the AFNOR NFT standard (72-150, March 1981) using benzalkonium chloride first as the active ingredient, then nonoxynol-9.

The neutralizing agents used were: 3% Tween 80 (v / v) 35 and 0.3% lecithin (w / v). The pH of the medium was 7.2.

S 9 675 23

Comparative Experiment No. 7 This experiment was performed without an activating ingredient.

Strains Minimum Inhibitory Concentration (PIP) 5 Benzalkonium chloride alone

Pseudomonas aeruginosa CNCM A 22 31.25 mg / l 10 Escherichia coli 6.57 mg / l CNCM 54 127

Staphylococcus Aureus 1.56 mg / l

Oxford origin CNCM 53 154 15

Streptococcus faecalis 4 mg / l CNCM 5,855

Mycobacterium smegmatis 30 mg / 1 20 CNCM 7 326

Strains Minimum Inhibitory Concentration (PIP)

Nonoxynol-9 -25 alone Pseudomonas aeruginosa CNCM A 22 50 mg / 1

Escherichia coli 8 mg / l CNCM 54 127 30

Staphylococcus Aureus 4 mg / l

Oxford origin CNCM 53 154

Streptococcus faecalis 7 mg / l 35 CNCM 5,855

Mycobacterium smegmatis 65 mg / l CNCM 7 326 89675 24

Experiment No. 8 This experiment is the same as described above, but was carried out in the presence of the fluoride anion F 'as an activating agent.

5

Strains Minimum Inhibitory Concentration (PIP)

Benzalkonium chloride + F "1 microgram / ml_ 10 Pseudomonas aeruginosa CNCM A 22 18 mg / l

Escherichia coli 3 mg / l CNCM 54 127 15

Staphylococcus Aureus 1.1 mg / l

Oxford origin CNCM 53 154

Streptococcus faecalis 3.6 mg / l 20 CNCM 5,855

Mycobacterium smegmatis 26 mg / l CNCM 7 326 25 89675 * Strains Minimum Inhibitory Concentration (PIP)

Nonoxynol-9 + F '1 microgram / ml 5 Pseudomonas aeruginosa CNCM A 22 35 mg / 1

Escherichia coli 6.5 mg / l CNCM 54 127 10

Staphylococcus Aureus 2.5 mg / l

Oxford origin CNCM 53 154

Streptococcus faecalis 5.5 mg / l 15 CNCM 5,855

Mycobacterium smegmatis 50 mg / l CNCM 7 326 20 III) Use of the invention in cosmetology

Preferred cosmetologically useful embodiments of the invention are described below:

The following galenic forms can be used cosmetologically: creams, milks, ointments, solutions, foam baths, synthetic soaps, shampoos, intimate solutions, disinfectant solutions.

The cosmetic products preferably contain 0.2% benzalkonium chloride and 0.1% fluoride anion F '(e.g. sodium fluoride).

In creams and milks, the excipients are preferably: distilled or purified water, humectants, emulsifiers, stabilizers, antioxidants, antiseptics (used in varying proportions depending on the desired viscosity and pH).

26 S9675

In ointments, the excipients are preferably: distilled or purified water, emulsifiers, fatty excipients (petrolatum, lanolin, lanovaseline, stearovaseline), stabilizers, antioxidants, antiseptics (used in varying proportions depending on the desired viscosity and pH).

In solutions, the excipients are preferably: distilled or purified water, ethanol, antioxidants, glycerin, sorbitol, antiseptics (used in varying proportions depending on the desired pH)

In soaps, the excipients are preferably: foaming and wetting products compatible with quaternary ammonia (for example an amphoteric surfactant such as betaine or aminobetaine), plasticizers, stabilizers, antioxidants, antiseptics.

20 These preparations may also contain chemical or naturally occurring active ingredients in concentrations and doses permitted in cosmetology.

Creams and milks may be in a continuous aqueous phase (oil-in-water or water-in-oil emulsion) or may be in the form of a warm paste, self-diluting in water.

The various excipients mentioned by way of example are, by way of illustration and without limitation to the invention, the following products:

Wetting and diluting agents: glycerol, propylene glycol, diethylene glycol, glycol, sorbitol, polyoxyethylene glycol.

35 Emulsifiers: sodium stearate, beeswax, sorbitol ester, polyoxyethylene glycol ester, fatty alcohol, triethanolamine amanolin, Tween, glycol stearate and polyglycols.

8 9 675 27 * Stabilizers: glycol stearate, cetyl alginate alcohol, pectin, gum, fatty acid esters of polyols, soluble cellulose esters.

5 Antioxidants: tartaric acid, citric acid and as-corbic acid.

Antiseptics: boric acid, benzoic acid, parabenzoic acid and their methyl and propyl esters, whether or not containing sodium.

pH: All of these products are particularly effective when their pH is in the range of 4.5 to 6.5. Citric acid is mainly used to reach such pH values.

15

Claims (13)

1. A non-pharmaceutical composition, characterized in that it contains an effective amount of a surfactant suitable for inhibiting or destroying a single cell organism or virus, and an anti-enzymatic amount of a fluorine compound capable of delivering fluorine ions and suitable for inhibiting or destroying an enzyme associated with the single organism or virus, wherein the amount of fluorine ions which can be released is 0.025-0.5% by weight, and that it is used as a contraceptive, disinfectant or antiprotoxic agent or in a cosmetic product. Composition according to claim 1, characterized in that the fluorine compound is a metal derivative of fluorine. Composition according to claim 1 or 2, characterized in that the fluorine compound is sodium fluoride, calcium fluoride, potassium fluoride, aluminum fluoride, tin fluoride, ammonium fluoride or sodium monofluorophosphate. 8 9 675 30 Composition according to any of the preceding claims, characterized in that the surfactant is a cationic surfactant. 5. Composition according to any of the preceding claims, characterized in that the surfactant compound is a quaternary ammonium. Composition according to any of the preceding claims, characterized in that the surfactant compound is benzalkonium chloride. 7. A composition according to any one of claims 1-3, characterized in that the surfactant is an anionic surfactant. Composition according to any one of claims 1-3, characterized in that the surfactant is an amphoteric surfactant. 20 9. A composition according to any one of claims 1-3, characterized in that the surfactant is a nonionic surfactant. Composition according to any of the preceding claims, characterized in that the surfactant is a sodium oxide salt of methyl tauride, an amidoethyl glycinate derivative of a fatty acid, nonoxinol, phenyl mercury (II) nitrate, para-butanylphenylpolyoxyethylene ether or sackaridsvavelsyraeter. Composition according to any of the preceding claims, characterized in that it contains 0.05-1% by weight of the surfactant compound.