IL34659A - An antiseptic composition comprising a germicidal quaternary ammonium compound,a poly(oxyethylene)-poly(oxypropylene)-block polymer and a local anaesthetic - Google Patents

Description

AN ANTI SEPTI C COMPOSI TION COMPRI SING A GERMI CI DAL QUATERNARY AMMONI UM COMPOUND, A POLY (OXYETHYLENE)«S POLY (OXYPROPYLENE)-BLOC POLYMER AND A LOCAL ANAESTHETI C i aiya DI*J IBK naiam n *aan Π»ΒΒΟ»Β3Κ nanyn 'Bipa wnVsa ·»ϊηι - c .o er- IsraeI-980 This invention relates to antiseptic compositions, to processes for their preparation and to articles incorporating the compositions.

The use of quaternary ammonium compounds as ingredients of germicidal compositions for topical application is known, and so is the use of combinations of such compounds with local anaesthetics of the "caine-type" in solutions for surgical dressings.

It has now been found that the addition of certain quantities of a pol (oxyethylene ) -poly(oxypropylene) block polymer to the above combination forms a composition which is particularly useful for topical application to treat minor skin wounds.

According to the present invention there is provided a substantially non-stinging antiseptic composition comprising an aqueous solution of a germicidal quaternary ammonium compound, a local anaesthetic, and a pol (oxyethylene) -pol (oxypropylene )-block polymer in an amount of from 2 to 15$ by weight based on the total weight of the composition. The presence of a poly(oxyethylene)-poly(oxypropylene)-block polymer in an amount of from 2 to 1 $ by weight results in a -- c o er- Israel-980 synergistic effect being displayed whereby the anaesthetic activity of the composition is greater than when no block polymer is present.

The composition is most advantageously sugLied as impregnant of a sheet material enclosed in a hermetically sealed packet. The said packet fully exploits all the beneficial properties of the composition.

The novel composition can be used to treat minor skin wounds, abrasions, burns and similar first aid problems and as such is useful in fighting infection, relieving pain on contact and generally soothing the injured area. Furthermore, this antiseptic action is effected without a stinging sensation thus rendering these compositions especially valuable for treating children and pets who are often reluctant to receive commonly used first aid treatments because of their stinging effect. Moreover, shortly after appli cation, these compositions air-dry and deposit an invisible film which prolongs the activity and aids in protecting the injured area from further immediate contamination.

AFR-1-1970 980-FTE-3 IK-ug As described below in more detail , the effect of the said composition can be further increased when applying it by means of a sheet material of e . g. non-woven rayon.

The germicidal quaternary ammonium compounds are generally used in the form . of their halides and preferably as chlorides. Preferred quaternary ammonium compounds for use in the compositions of this invention are so-called alkylarylether dimethylbenzylammonium chlorides, an example of which is (2- 2- (p_-octylcresoxy) ethoxy ethyl dimethylbenzylammonium chloride, available under the name of methylbenzethonium chloride or Eyamine 10X and the corresponding p-octylphenoxy compound availal le as benzethonium chloride or Hyamine 1622 j and the alkyl-dimethylbenzyl ammonium chlorides available under the name benzalkonium chlorides. Other suitable germicidal quaternary ammonium compounds are alkyltrimethyl ammonium chloride, such as cetyltrimethylammonium chloride available under the trade name Cetab alk ldimethyl-ethylammonium halide such as alkenyldimethylethylammonium bromide known under the trade name Onyxide ,° alkylpyridinium chloride , such as cetylpyridinium chloride ; alkylimidazolinium chloride such as alkylhydroxyethylimidazolinium chloride known as Alrosept MB ? alkyldimethyldichlorobenzylammonium chloride such as alkyld.imethyl-3 , 4-dichloro benzylammonium chloride known as Tetrosan ; acylcolaminoformylmethyl APR-1-1970 m 980_FTE~.4 IK-ug and alkarylmethylpyridinium chloride such as polyalkyl-naphthalene methylpyridinium chloride available under the trade name Emcol. In the foregoing compounds the term "alkyl" is understood to encompass radicals including mixtures within this range , this being the range in which quaternary ammonium compounds are considered to have good germicidal activity.

The preferred sub-class of local anesthetics for use in a composition of this invention are those amino -substituted phenyl esters and amides distinguishable by having a generic name ending in the syllable !'caine".

This class of local anesthetic compounds will be referred to hereinafter as "caine-type" . Exemplary of these are lidocaine, tetracaine, benzocaine, procaine, cocaine, mepivacaine and bupivacaine. These can be used as the free base or in a form of their pharmaceutically acceptable acid addition salts, particularly as the hydrochlorides . Preferred local anesthetics for use in compositions of this invention are tetracaine and lidocaine. -¾¾¾¾s^:i¾:ga¾^:?u g¾¾¾^ The ' poly (oxyethylene) -poly (oxypropyler-e) block polymers to be used in the composition of this invention are also well known in the art and may be represented by the structural formula s HO(C2H40)a(C3H60)b(C2H40)cH wherein the represents the polyoxypropylene hydrophobic base component and the HO(C H.0) and i 4 a (C2H40)cH represent the polyoxythylene hydrophilic constituents. The polyoxyethylene portion of the polymer may v? ry from as little as 10 percent to as high as 90 percent, preferably from 65 to 85 percent. The higher the polyoxyethylene percentage, the more water-soluble APR- 1-1970 980-FTE-5 IK~ug becomes the total molecule or polymer . The substantially-water-soluble polymers in the molecular weight range of between about five and about eleven thousand are preferable. These materials are readily available under the tradename Pluronic polyolu ara are dise ased e.g. in the U.S.. Patent specification No. 2,674,615. A preferred material of this class for use in the ccmpostions of this invention is available under the trade name of Pluronic F68 and has an average molecular weight of about 8350 f although it may vary in range between about 5000 and 9C00. In thiimmaterial "a" and "c" in the above formula can, for example , each be near or equal to 72 and "b* can be near or equal to 26. The polyoxyethylene portion of this material is about 30 %.

Both the antimicrobial quaternary ammonium compounds and the local anesthetics should desirably be present in the aqueous composition of this invention in a range of 0,05 to 3% by weight preferably o,l to 2 ¾. The poly (oxyethyiene) -poly ( xvpropylene) block polymers should desirably be present in the amount of 2 to 15 ¾ by weight o the total composition and preferably 3 to 7 ¾ .

The aqueous com si i ns of this invention can optionally contain , in addition to the above ingredients , other materials to maximize effectiveness.

Monionic polyethenoxy surface active agents s . h as the well-knovm polyethenoxy mono-ether , polyethenoxy mono- ste and polyethenoxy mono-amides are advantageously included in the composition of th s invention, preferably in an amount of '¾ 2 to 35 by weight of the compos tion, Thene nonionic surface active agents provide detergent action to a much grater extent than the free polyoxyethylene-poiy-oxy ropylene block polymer polyols . Such compounds .arc well-known in the art. The preferred class of materials of this type for use in- this invention are the polyethenoxy mono-ethers of alkylphenols as exemplified by polyethenoxy mono-isooctylphenylether , availalbe under the trade name Triton X-100, and polyethenoxy mono- nonylphen lether.

Desirably, the composition of this invention also included a humectant such as propylene glycol, glycerine, sorbitol, di-ethylene glycol or polyethylene glycol. In addition to- .their humectant effect, these materials also serve in aiding dissolution or emulsion of the composition of this invention. These materials are desirably employed within the range of about 1 to 10%.

A chelating agent such as for example ethylenediamine tetraacetic acid (EDTA) can optionally be added to enhance the antibacterial activity of these compositions.

A minor amount (e.g. 3%) of isopropanol can be added to impart a "medicinal odor". Similarly, a small amount (e.g. 0.5%) of menthol provides a soothing "cool feeling".

Calming an injured child or other patient is a desirable part of first aid treatment.

Auxiliary medicaments may be incorporated into the composition of this invention to broaden the scope of treat-ment, as for example, the inclusion of a minor amount of chlorothyrool to impart fungicidal properties.

The composition octm ¾y mixing the ingredients described above with an aqueous solvent. The compositions of this invention can be applied to the injured area in numerous ways. They can be directly applied from a squeeze bottle or dropper, for example, or sprayed on employing an aerosol cannister containing a conventional propellant such as the Freons. Alternatively, a swab can be introduced into a container of the formulation and saturated therewith and applied to the injured area. Similarly, the solutions can be applied by means of a handkerchief or other extraneous cloth or tissue. Each of these methods has disadvantages, however, with regard to convenience, hygiene and/or effectiveness.

As a highly preferred embodiment of this invention, we have found that the maximum benefit of the compositions of this invention can be realized by applying the said composition by means of a pad. The most preferred embodiment is a packet containing a pad impregnated with these compositions. The pad should be an absorptive sheet of a material dispensing the essential ingredients of the composition at a suitable rate. Preferably the sheet is made of non-woven cellulosic material. Non-woven rayon has been found to be particularly good for this purpose.

The packet should be impervious to liquid or vapor, i„e. substantially impermeable for the ingredients of the composition, and its interior should be inert to the composition of this invention. Such packets are well-known in the art and preferably comprise an outer surface of a metal foil such as aluminium whose inner surface is lined with a thermoplastic film such as polyethylene, polyvinyl resin or cellulose acetate as described, for example, in U.S. Patent Specification No. 3,057,467. A laminate having an intermediate layer of paper is an advantageous variation. Suitably such packets are hermetically sealed. This sealed packet protects both the composition and the applicator against contamination occurring after manufacture and before application to the wounded area.

The invention in this preferred embodiment furthermore IK/jb thoroughly of dirt and other particles. Thus, it aids in preventing further infection by removal of superficial organisms that have not yet infected the wound, and by prophylaxis of the surrounding area, while at the same time fighting infection by any organisms already in the wound. Use of this pad also permits the application of a thin uniform coating of the composition, thereby minimizing the time necessary for the skin to dry and the film to form. In this embodiment it is preferred that the compo-sitions additionally contain a non-ionic polyethenoxy surface active agent as described above to further aid in the cleansing operation.

This preferred embodiment provides an ideal means to have the compositions of this invention readily available at the time the injury is sustained since it can be carried in the pocket, handbag, as well as stored on vehicles or at home or work. The entire packet is inexpensive enough to be disposed of after a single use. Moreover, the open foil packet provides a hygienic place to temporarily store the used pad until suitable disposal facilities become available.

The following examples illustrate preferred embodiments of this invention.

Example 1 A piece of non-woven rayon pad measuring 8 x 9 cm is folded longitudinally and transversely and is inserted into a pouch formed by two sheets of a laminate of aluminium foil and paper, coated (on the paper side) with polyethylene. Two milliliters of a formulation consisting of ; 980-FTE-9 IX/jb methylbenzethonium chloride 0.5% tetracaine hydrochloride 0.6% polyoxyethylene-polyoxypropylene 5.0% (Pluronic F68) polyetlenoxy alkylaryl ether 2.0% (Triton X100) propylene glycol 3.0% isopropyl alcohol 3.0% menthol 0.1% purified water 85.8% are injected into the folds of the pad and the aluminium laminate is then heat sealed on the open fourth side to complete the packet.

The pad could alternatively be folded in a "zigzag" or "accordion-pleating" fold.

Example 2 A formulation consisting of benzethonium chloride 1.5% lidocaine hydrochloride 1.7% polyoxyethylene-polyoxypropylene 6.0% polyethenoxy mono- 0.5% nonylphenylether ethylenediamine tetraacetic acid x£fex.

(EDTA) 0,5 purified water 89.8% is filled into a squeeze bottle.

Numerous other variations of the above-described non- stinging products and processes that within the spirit of 30 this invention v/ill become apparent to one skilled in the art.

Claims (22)

34659/2 WHAT IS CLAIMED IS:

1. A substantially non-stinging antiseptic composition comprising an aqueous solution of a germicidal quaternary ammonium compound and a local anaestheti c» characterised in that it also contains a poly(oxyethylene)-poly(oxypropylene)-block polymer in an amount of from 2 to 15% by weight based on the total weight of the composition*

2. A composition according to claim 1, wherein said local anesthetic is of the "caine-type".

3. A composition according to claim 2, wherein said local anesthetic is tetracaine or lidocaine.

4. » A composition according to any one of claims 1 to 3 which additionally contains a non-ionic surface active agent such as for example polyethenoxy mono-ethers » polyethenoxy mono-esters and polyethenoxy mono-amides*

5. · A composition according to claim 4, wherein said additional surface active agent is a polyethenoxy mono-alkylaryl ether.

6. A composition according to claim 5s wherei said block polymer is Pluronic F68 having the ormula HO(C2H0)a (C3H60)b

7. * A composition according to any one of claims 1 to 6» wherein said block polymer has an average molecular weight between about 5000 and 11000. APR- 3- 1970 980-FTE-ll IK/jb

8. » A composition according to claim 7 , wherein said block polymer has an average molecular weight between about 6000 and 9000 .

9. O A composition according to any one of claims 1 to 8 , which additionally contains at least one of the following ingredients; a humectant, such as for example propylene glycol, glycerine, sorbitol, di-ethylene-glycol or polyethylene-glycol ; a chelating agent, such as for example ethylene-diamine-tetraacetic acid (EDTA) enhancing the antibacterial activity of this composition; chloro-thymol; a substantially non-toxic lower alkanol such as for example isopropanol; and menthol.

10. . A composition according to any one of claims 1 to 9 comprising about 0 , 05 to 3 % by weight, preferably 0 , 1 to 2 % of the quaternary ammonium compound.

11. . A composition according to any one of claims 1 to 10 comprising about 0 , 05 to 3 % by weight, preferably 0 , 1 to 2 % of the local anesthetic.

12. . A composition according to any one of claims 1 to 11 comprising about ¾ to 15% by weight, preferably 3 to 7 % of the said block polymer.

13. . A sheet material which has the property to absorb the composition of any one of claims 1 to 12 and to dispense the essential ingredients thereof at a suitable rate, and which is impregnated with the said composition.

14. . A sheet according to claim .13 which is made of a cellulosic material.

15. . A sheet according to claim .14 , characterized in that the cellulosic material is non-woven.

16. Λ sheet according to claim 15, which is made of non-woven rayon.

17. A packet containing a sheet material according to any one of claims 13 to 16» said packet being substantially impermeable for the ingredients of the composition of any one of claims 1 to 12.

18. A process for the preparation of a substantially non-stinging antiseptic composition according to claim 1 characterized in that a germicidal quaternary ammonium compound» a local anesthetic and a polyCoxyethylene)-poly (oxypropyleae)-block polymer are mixed with an aqueous solvent as a carrier.

19. A process according to claim 18» characterized in that the ingredients of a composition defined in any one of claims 1 to 12 are mixed.

20. the process of claim 18 or 19» which includes absorption of the composition by a sheet material as defined in any one of c aims 13 to 16.

21. A process for the preparation of a non-stinging antiseptic composition substantially as hereinbefore described} with particular reference to the Examples.

22. A non-stinging antiseptic composition when prepared by a process according to any one of claims