ANTIBACTERIAL AND SPERMICIDAL LUBRICANT

Abstract

The invention relates to a chemical composition, which contains at least one polymeric guanidine biocide and at least one alkylphenoxy polyethoxyethanol spermicide in an aqueous solution, and at least one thickener, and which is suitable as a biocidal and spermicidal agent for use during intercourse.

Claims

1. A chemical composition containing at least one polymeric guanidine biocide and at least one alkylphenoxypolyethoxyethanol spermicide or a local anesthetic, in aqueous solution, and at least one thickening agent.

2. The composition as claimed in claim 1, characterized in that the polymeric guanidine biocide is a polyalkylene guanidine, preferably a polyoxyalkylene guanidine.

3. The composition as claimed in claim 2, characterized in that the polymeric guanidine biocide is selected from polyhexamethylene guanidine; poly[2-(2-ethoxy)ethoxyethyl guanidinine; polytriethyleneglycol guanidine; polyethyleneglycol guanidine; polyoxypropylene guanidine; polyoxyethylene guanidine.

4. The composition of claim 1, characterized in that the guanidine is a guanidinium salt, preferably selected from a halide, preferably a chloride; phosphate, preferably a dihydrogen phosphate; carbonate; nitrate; sorbate; acetate, preferably hydroacetate; gluconate, citrate, silicate.

5. The composition of claim 1, characterized in that the mean molecular weight of the polymeric guanidine biocide is 200 Da to 10000 Da, preferably 500 Da to 3000 Da.

6. The composition of claim 1, characterized in that the alkylphenoxypolyethoxyethanol spermicide is nonylphenoxypoly(ethyleneoxy) ethanol (nonoxynol-9).

7. The composition of claim 1, characterized in that the thickening agent is a gel forming agent, preferably selected from hydroxyalkyl cellulose, cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose; or a suppository base, preferably selected from hard fat, a glycerol-gelatine mixture or soluble PEG, for example PEG 400/4000.

8. The composition of claim 1, characterized in that the composition comprises 0.05% to 10% (by weight) of polymeric guanidine biocide.

9. The composition of claim 1, characterized in that the composition comprises 0.05% to 8% (by weight) of alkylphenoxypolyethoxyethanol spermicide.

10. The composition of claim 1, characterized in that the composition comprises 1% to 95% (by weight) of thickening agent.

11. The composition of claim 1, characterized in that the composition is in a single dose form in a quantity of 1 mL to 5 mL, preferably in a disposable pipette.

12. The composition of claim 1, characterized in that the composition contains a humectant, preferably propylene glycol.

13. The composition of claim 1, characterized in that the composition contains the following: polymeric guanidine biocide: 0.05% to 10%, humectant: 5% to 15%, alkylphenoxypolyethoxyethanol spermicide: 0.05% to 10%, thickening agent: 1% to 10%, all as a % by weight, preferably further containing: Acidum Ascorbicum 0% to 3%, sodium hydroxide: 0% to 2%, citric acid: 0% to 4%, Aqua purificata: remainder to 100%, all as a % by weight.

14. A method of disinfecting a vagina in a subject during sexual activity, comprising introducing into the vagina of the subject chemical composition containing at least one polymeric guanidine biocide in aqueous solution, and at least one thickening agent.

15. A method for preventing infection with a sexually transmittable disease or for contraception during sexual activity, comprising introducing a composition of claim 1 into a vaginal canal for the sexual activity.

Description

[0082] The figures show the inhibiting action of the composition in accordance with the invention and pure Akacid in different concentrations of the substance against various pathogens, namely against MRSA1 (FIG. 1), EK4 (FIG. 2), Strepto 8 (FIG. 3), E. coli 13 (FIG. 4), KL 37, (FIG. 5), PS23 (FIG. 6), Asp. fum. 45 (FIG 7), Asp. faec. 46 (FIG. 8), C. albicans (FIG. 9), C. krusei (FIG. 10), in each case together with positive controls (PC) and negative controls (NC).

EXAMPLE 1

Production of a Polyguanidine Formulation

[0083] The basic formulations were biocidal substances from the polyguanidine group (Akacid, described in Kratzer et al., Antibiotika Monitor Jan. 2, 2006; Buxbaum et al., Journal of Antimicrobial Chemotherapy (2006) 58,193-197; WO 01/85676 A1; WO 2006/047800 A1; WO 2008/080184 A2; WO 2013/064161 A1), in various formulations such as Akacid Plus (3:1 mixture of polyhexamethylene guanidinium chloride and poly-[2-(ethoxy)eyethyl]guanidinium chloride). These biocidal polymeric guanidine compounds have an excellent antimicrobial profile and in addition are capable of delivering stable formulations with substances which are difficult to mix without solubilizers from the group formed by polyethoxylated non-ionic compounds.

[0084] Akacid was produced in a modified method in which the starting substances tri ethylene glycol with hexamethylenediamine and guanidine hydrochloride were reacted in a 1-step synthesis and then freed from low molecular weight and high molecular weight monomers by filtration through three NF membranes so that a monomeric purified Akacid Plus fraction with. better pharmacological properties was produced. The mass average molecular weight of this Akacid Pius (or X-Cid was approximately 1000 Dalton (mainly 500 to 3000 Dalton). The composition was prepared as an aqueous solution for further formulation.

[0085] The quantities of the substances are given in g or as a %. All of the percentages are given as a % by weight, unless indicated otherwise.

EXAMPLE 2

Liquid Condom Female Formulation

[0086] The liquid condom female formulation consisted of a gel containing hydroxyethylcellulose. The hydroxyethylcellulose was expanded with Aqua Purificata for 5 minutes until a low viscosity gel was obtained.

[0087] A citric acid solution was incorporated into this gel base; the pH was adjusted to 5.5-6.2 by means of a sodium hydroxide solution after mixing in all of the other substances.

[0088] The two active substances Akacid Plus 1000 (in a concentration of 0.2-1%) and the spermicidal substance 9-nonoxinol (in a concentration of 5%) or other substances which promote contraception such as lactic acid, citric acid, quinine, pomegranate seed extract, honey or crushed acacia shoots were incorporated into the prepared gel base. Administration of the gel was carried out using 1.8 mL disposable plastic pipettes the head of which had to be twisted off before use. The total amount has to be inserted intravaginally at least 1-3 minutes prior to sexual intercourse. The gel is then distributed by the sexual activity itself.

[0089] Formulation I, Liquid Condom Female:

TABLE-US-00001 Akacid Plus 1000, 50% 0.8 g (i.e. 0.4 g Akacid) Acidum Citricum 1.5 g propylene glycol 10.0 g nonoxynol-9 5.0 g hydroxyethylcellulose 2.0 g sodium hydroxide 0.75 g Aqua purificata 79.95 g 100.0 g

EXAMPLE 3

Liquid Condom Male Formulation

[0090] The liquid condom male formulation is a hydroxyethylcellulose-containing gel. The hydroxyethylcellulose was expanded with Aqua Purificata for 5 min. until a low viscosity gel was obtained with shearing. The two active substances Akacid Plus 1000 (for example in a concentration of 0.2%) and the local anesthetic lidocaine hydrochloricum (in a concentration of 0.4%) were incorporated into the ointment base which had been produced. The local anesthetic was added for the purposes of desensitization in order to counteract premature ejaculation. The pH here was neutral to slightly basic. The formulation did not have a contraceptive action and primarily serves to prevent infection of the male by otherwise unprotected sexual intercourse.

[0091] Formulation II Liquid Condom Male:

TABLE-US-00002 Akaoid Plus 1000, 50% 0.6 g (i.e. 0.3 g Akacid) propylene glycol 3.0 g hydroxyethylcellulose 3.0 g lidocaine hydrochloricum 0.4 g Aqua purificata 93.0 g 100.0 g

EXAMPLE 4

Liquid Condom Suppository Formulation

[0092] The weighed Akacid Plus 1000 was incorporated into the molten Adeps Neutralis solution together with the nonoxynol-9, and after cooling to approximately 40-45 C. was cast into 2 g suppository moulds and allowed to cool and solidify.

[0093] Formulation III Liquid Condom Suppository 1%, 10 Pieces:

TABLE-US-00003 Akacid Plus 1000, 50% 0.4 g (i.e. 0.2 g Akacid) Adeps Neutralis 19.0 g nonoxinol-9 1.6 g 21.0 g

EXAMPLE 5

Comparison of Antibacterial Effect of the Liquid Condom Compared with Pure Akacid

[0094] The following compositions were tested by comparison with each other, wherein only the Akacid concentration (as Akacid Pius as described in Example 1) was varied, in a variety of dilutions.

[0095] Composition I: liquid condom as described in Example 2(liquid condom female) with nonoxinol-9

[0096] Composition 2: liquid condom as described in Example 2(liquid condom female) without nonoxinol-9(water instead)

[0097] Composition 3: Akacid Plus, remainder: water

[0098] Pathogens tested: [0099] MRSA 1Staphylococcus aureus [0100] EK 4Enterococcus taecium [0101] Strepto 8Streptococcus pneumoniae [0102] E. coli 13Escherichia coli [0103] KL 37Klebsiella pneumonia [0104] PS 23Pseudomonas aeruginosa [0105] Asp. fum. 45Aspergillus fumigatus [0106] Ssp. faec. 46Aspergillus fumigatus [0107] C. alb.Candida albicans [0108] C. Krusei 26Candida krusei

[0109] Media:

[0110] For bacteria: Mller Hinton Broth

[0111] For fungi: Sabouraud Broth

[0112] Assay:

[0113] 50 L of the respective medium was placed in all of the wells of 96-well plates, with the exception of the control wells, into which 100 L of medium per well was added. Samples were prepared and 100 L thereof was added to the wells.

[0114] 50 L of the test compositions was added to the wells, wherein the test compositions had different X-cid concentrations, starting from 0.6%, and respective 1:1 dilutions with the remaining composition components, i.e. 0.6%, 0.3%, 0.1%, 0.075%, 0.07%, 0.0188%, 0.00938%, 0.00469%, 0.00234%, 0.00117% (rounded, all percentages as % by weight).

[0115] Pathogen samples were thawed and diluted in the respective medium. 50 L of the pathogen sample was added to all of the wells (apart from the negative control). Incubation was carried out overnight at 35 C. On the following day, the plates were visually assessed and measured using the SpectraMax 190 reader.

[0116] The results of the measurement with the SpectraMax 190 reader are shown in FIGS. 1-10.

[0117] Clearly, with MRSA there was a liquid condom activity in all of the concentrations. Individual outliers were assumed to be due to possible unequal quantities of material being transported with the pipette. This might be possible because the substance itself was very viscous, and thus it was sometimes difficult to pipette exact quantities.

[0118] This was also the case for the liquid condom with nonoxynol.

[0119] For Akacid 7 (=X-Cid test substance), an activity up to a concentration of 0.009375% could be observed. After this, no more inhibition could be obtained.

[0120] With EK 4, the liquid condom activity could be observed up to a concentration of 0.08175%, while the liquid condom activity in combination with nonoxynol could be observed up to a concentration of 0.009375%.

[0121] Akacid 7 was active up to a concentration of 0.0375%. Surprisingly, this means that the liquid condom was more effective than pure Akacid for the same Akacid concentration. This can only be assumed to be due to a synergistic effect of the composition.

[0122] With Streptococcus 8, variations in the visibility of the activity were again present, so that a true inhibition could only be obtained in the first two concentrations.

[0123] For Akacid 7, an activity against streptococcus 8 could be observed up to a concentration of 0.0046875%.

[0124] For E. coli 13, variations in the activity for the liquid condom as well as for the liquid condom in combination with nonoxynol were again observed. For Akacid 7, there was activity up to a concentration of 0.01875%.

[0125] For KL 37, the activity of the liquid condom was observed up to a concentration of 0.009375%, while activity of the liquid condom in combination with nonoxynol was observed up to a concentration of 0.0046875%. For Akacid 7, an activity of up to a concentration of 0.0375% could be observed.

[0126] For PS 23, the activity for Akacid 7 was up to a concentration of 0.0375%. For the liquid condom and the combination of liquid condom and nonoxynol, an inhibition of activity was observed up to a concentration of 0.01875%.

[0127] For Aspergillus fumigatus 45, the activity of the liquid condom and the combination of liquid condom with nonoxynol was observed in almost all concentrations (up to 0.00118%minimum tested concentration). For Akacid 7, the activity was only obtained up to 0.009%. For Aspergillus fumigatus 46, the activity for the liquid condom as well as for the combination of liquid condom with nonoxynol was present at 0.6%. For Akacid 7, the activity for a concentration of 0.15% was observed. With Candida albicans, the activity for the liquid condom as well as for the liquid condom in combination with nonoxynol was 0.3%. For Akacid 7, the inhibition was visible up to a concentration of 0.075%.

[0128] For Candida krusei 26, the inhibition for Akacid was the highest compared with liquid condoms and the combination of liquid condom with nonoxynol, and in fact with an inhibition up to a concentration of 0.08175%. For the liquid condom, inhibition up to a concentration of 0.075% was visible. For liquid condoms in combination with nonoxynol, inhibition was observed up to a concentration of 0.0375%.

[0129] In summary, almost no difference or only a very small difference was observed between the liquid condom alone and liquid condoms with nonoxynol. However, in most cases, Akacid 7 exhibited a lesser inhibiting effect compared with the two liquid condom compositions.