MXPA97003784A - Compositions germicides detergente-yodo queincluyen polivinilpirrolidona and trainers of complex surfactants, non-ionic, compatib - Google Patents

Abstract

The present invention relates to an aqueous, stable, complex iodine-forming germicidal composition, characterized in that it comprises an average amount of available iodine in a nominal base and from about 2 to about 4.5 parts of complexing agent per average available iodine, the complexing agent comprising individual amounts of polyvinylpyrrolidone and a surfactant complex former, the composition having a sufficient amount of the complexing agent to remain homogeneous after one week storage at temperatures of 2 ° C and 40 ° C.

Description

COMPOSITIONS GERMICIDES DETERGENTE-YODO THAT INCLUDE POLIVINILPIRROLIDONA AND FORMATORS OF SURFACTANT, NON-IONIC, COMPATIBLE COMPLEXES Related Requests: This is a continuation in part of Application Serial No. 08 / 163,596 filed December 6, 1993, now Patent No. 5,368,868, which is a continuation of Application Serial No. 07 / 947,041, filed on October 18, 1993. September 1992, now abandoned.

Background of the Invention Field of the Invention The present invention is broadly related to the improved, stable germicidal compositions of iodine-forming agent, and to concentrates that can be diluted to provide such compositions, useful for topical applications to the skin of humans or animals, which they have relatively low proportions of average available agent / complexion / iodine. Plus REF: 24698 in particular, this is related to such concentrates and compositions of use wherein the proportion of average available complexing / iodine agent (s) are in ranges from about 2: 1 to about 4.5: 1, and wherein the fraction of the complexing or complexing agent preferably comprises a polyoxypropylene-polyoxyethylene block copolymer having a molecular weight of the central polyoxypropylene (POP) of at least about 2600 and a polyoxyethylene (POE) content of the order of 30% -75% in weigh. It has been found that the use of complexing agents or complexing agents, specific to this character, produce compositions and concentrates for germicidal use, stable at high and low temperature, of low proportion. In yet another aspect of the invention, the use of the compositions and concentrates is provided with from about 2-4.5 parts of a complex component, two component agent, per available iodine part, and wherein the complexing agent includes individual amounts of polyvinylpyrrolidone (e.g., Povidone or PVP), and a compatible, non-ionic, complexing complexing complexer, surfactant, such as a polyethoxylated polyoxypropylene. 2. Description of the prior art Germicidal detergent-iodine products designed for topical application to the skin have been available for a long time. These formulations are mainly directed in products such as pre-operative antiseptic preparations, hand cleansers and in bovine teats for the prevention of mastitis. Apart from the detergent-iodine complex, these products typically include varying amounts of additives to provide pH control, emolliency, viscosity and in some cases a colorant. It is also known to provide germicidal compositions of Povidone-iodine for topical uses. In general, these prior compositions are characterized by relatively high levels of Povidone (e.g., a minimum ratio of Povidone: iodine of about 6: 1), which has been thought to be necessary in order to adequately complex the iodine , particularly for products of topical human use. US Patent No. 3,728,449 describes a wide range of germicidal detergent-iodine compositions specifically adapted for application to the tits of animals that give milk, for the control and prevention of mastitis. A number of iodine, non-ionic, ethoxylated iodine complexing or capping agents are described as effective in Patent 49, at a minimum ratio of 5 parts of complexing agents for each part of average available iodine. Among the complexing agents described in this patent are the nonylphenol ethoxylates, polyalkylene glycol ethers, polyoxyethylene sorbitan monolaurate and monopalmitate, polyvinylpyrrolidone and polyethoxylated polyoxypropylenes. This last type of complexing agent is referred to in the art as a "Poloxamer", which is a block copolymer based on a central portion of polyoxypropylene with polyoxyethylene groups at the respective ends of the central portion. There is a wide range of commercially available poloxamers having central portions in the molecular weight range of about 1000 to 4000, which have polyoxyethylene contents of the order of 10% -80% by weight of the total weight of the Poloxamer. In order to be reliable and useful for an end user, the compositions for germicidal use of the detergent-iodine and the concentrates thereof must be stable (eg, remain homogeneous) over a wide temperature range. If the stability is lost, and the products are separated, the usefulness of the compositions is significantly degraded and these can present a potential danger to the user. Generally speaking, stability in this context means that a given product should remain homogeneous after prolonged storage (for example, 1 week) at temperatures as low as 2 ° C (which can be experienced in warehouse storage areas). cold) or as high as 40 ° C, which may occur during the transport of the closed vehicle. Furthermore, although a given product can be separated when it is frozen, especially after undergoing several freeze-thaw cycles, it must be easily reconstituted with a homogeneous mixture after stirring or simple mixing. In addition, all detergent-iodine formulations have some of the iodide ion present which can vary as desired, from relatively high concentrations described in US Patent 3,028,299 to stabilized, relatively low values, shown in US Patent No. 4,271,149. In general, the levels of the iodide ion are in the range of about 0.3-1 part of iodide per part of iodine in the above formulations. As indicated above, detergent-iodine products designed for topical application to the skin are usually formulated with an amount of emollient. The most common emollients employed are glycerin, lanolin and its derivatives, sorbitol, fatty acid ester of polyhydroxy compounds, and propylene glycol. These emollients are used at levels in the range of from below 1% to as high as 10% in the use compositions. Glycerin is the most widely used emollient in bovine teats, and is also used extensively at low levels in human topical povidone-iodine and iodine-detergent formulations. Another desirable functional feature for germicidal detergent-iodine compositions designed for topical application is the ability to spread uniformly on the skin and not to drain off so quickly as to prevent insufficient contact time of the germicide. Many of the usual ingredients in detergent-iodine products contribute to viscosity. However, it is common for topical products to be formulated with a specific thickener to provide the added viscosity. There are many viscous modifiers of specificity, compatible with detergent-iodine systems, such as carboxymethylcellulose derivatives, polyacrylate derivatives, alginates, xanthates and polysaccharides. Those are typically used at levels below 1% by weight in a composition for end use. These types of ingredients, suitably selected, have a negligible effect on the homogeneity for a given composition of use. On the other hand, where dilutable concentrates are desired, viscosity modifying additives may become a problem and special care must be taken in the selection of the specific agents and their levels of use in the concentrates. As explained above, the prior art is replete with examples with detergent-iodine formulations having relatively high proportions of average available detergent / iodine, greater than 5: 1. U.S. Patent No. 3,728,449 describes a simple example at a ratio of 5: 1, which makes use of PVP as a complexing agent. The following lower rate example in this patent uses a nonylphenol ethoxylate at a ratio of 7.5: 1. Example IIID describes a composition constituted to include 5 parts of a poloxamer (Pluronic P123), but the average available detergent / iodine ratio of this example is 8: 1. There are a number of potential advantages in the use of very low proportions of average available complexer / iodine in germicidal iodine concentrates and use compositions designed for application to the skin or tissues. For example, in a low proportion product of this type, there would be less organic matter to react with the iodine, thereby making such compositions more stable with respect to the content of the available labeled or nominal iodine. Another advantage where the main complex is a detergent is that one would expect the reduced amounts of detergent to be less irritating to the skin, and could consequently refer a lower amount of emollients. Compositions with lower proportions of average available available iodine complexor could be formulated to have higher or more stable free or non-complex iodine levels. The use of nominal amounts of complexer would also allow the possibility of reduced water content in the concentrates, thereby correspondingly reducing the costs of packaging, shipping and storage. In the past, iodine-containing compositions have also been provided which include polyvinylpyrrolidone. Such compositions are especially those that conform to the requirements of the U.S.P. For topical solutions of Povidone-iodine, they have high proportions of Povidone to available iodine within the range of about 9: 1 to about 7: 1. Most commercial compositions of this type also contain a small amount of surface active agent, generally about 1% or less, to lower the surface tension and thereby aid diffusion. Such a surfactant additive is frequently of the non-ionic ethoxylated type, most frequently based on a non-phenyl ethoxylate. With proportions of Povidone to iodine in the aforementioned range, the contribution of the iodine complexation of the small amount of the nonionic surfactant employed is at best minimal. A topical poloxamer-iodine antiseptic ("Prepodyne") has been available for years for use in hospitals. This composition has a poloxamer ratio of the available iodine of about 5: 1, using poloxamers with an average molecular weight of polyoxypropylene and around 2600. However, there are no known prior compositions containing a two-component iodine complexer comprising Povidone and a non-ionic surfactant, where such a ratio of iodine-iodine complex is less than 5: 1. Accordingly, there is a real and unmet need in the art for improved compositions with a low proportion of complexer-iodine (and their concentrated dilutable counterparts) which have the required stability and germicidal utility, and which can be applied directly to the skin of an animal or a human.

Brief Description of the Invention The present invention overcomes the problems described above and provides desirable, stable, low-proportion aqueous compositions and concentrates, with iodine in complex, for application to the skin or tissues. The present invention in one aspect is based on the discovery that a certain limited class of polymers can be used with a part of such low proportion formulations, without sacrificing stability or other desirable qualities. In yet another aspect, the invention pertains to the improved detergent-iodine use compositions, and in concentrates that include from about 2 to about 4.5 parts of a two-component complexing agent, by the available iodine, in wherein the complexing agent includes individual amounts of polyvinylpyrrolidone and a compatible nonionic surfactant complex former.

Generally speaking, compositions for use according to the first aspect of the invention include about 0.1% -1.3% by weight of average available iodine in a nominal base and from about 2 to about 4.5 parts of polyethoxylated polyoxypropylene complexing agent. (Poloxamer) by average available iodine, wherein the polyoxypropylene portion has an average molecular weight of at least about 2,600 and a polyoxyethylene content of from about 30% to about 75% by weight. The pH of the use compositions is adjusted to the level of about 2-7. In the preferred forms, the poloxamer is selected such that the polyoxypropylene portion thereof, has an average molecular weight of from about 2,600 to 4,000, and more preferably from about 3,000-4,000, while the polyoxyethylene content may be in the range from about 30% to about 75% by weight for certain types of compositions, and from about 30% -50% by weight, or 30% -40% by weight, for other types of compositions within the scope of the invention. The pH of the aqueous use compositions is about 2-6.5, and may be in the range of about 2-4 or 4-6.5, depending on the composition in question; in general, lower pHs give more stable compositions. The compositions should also contain from about 0.2-1, and more preferably from about 0.3-0.5 parts of iodide from available iodine. The compositions of the first aspect of the invention may also include a number of other ingredients, for example an emollient which could typically be present at a level of about 0.1% -10% by weight, and more preferably from about 1% -5% in weigh. Suitable emollients can be selected from the group consisting of glycerin, sorbitol, propylene glycol, lanolin, ethoxylated lanolin derivatives, and mixtures thereof. Likewise, a buffering agent, such as those selected consisting of the citric, lactic, acetic and phosphoric acid salts and mixtures thereof, typically at a level of about 0.1, could also normally be present for pH control. % -1% by weight, and more preferably from about 0.2% -0.5% by weight. The first aspect of the invention also comprises aqueous germicidal concentrates adapted for dilution with water, to form a resulting use composition. In such a case, the concentrate could comprise from about 1% -5% by weight of average available iodine in a nominal base, and from about 2-4.5% parts of poloxamer complexing agent of the type described above, by iodine Average available. Other variable constituents of the concentrate could correspond, in appropriately higher amounts, to those described above in relation to the end-use compositions. The compositions of this invention are unique in that they represent the most efficient iodine complexing-solubilizers, ever described. There are no other known organic substances, of any type that can solubilize iodine at such low proportions of complex iodine in compositions suitable for application to the skin. Of course, the only substance that is somewhat more efficient to solubilize iodine in a base by weight, is the iodide ion (I ") same. As little as about 1: 1 iodide / iodine can be used to solubilize iodine in water, such as the known 2% Topical Iodine Solution (USP), but such preparations are of little practical use Nowadays, it is considered that these are too irritating to the skin.

In the second aspect of the invention, the compositions and concentrates of use, of complexer-iodine likewise contain from about 2 to about 4.5 p of complexing agent per pof available iodine; in this case, however, the complexing or complexing agent which is composed of a combination of individual amounts of polyvinylpyrrolidone and a compatible, non-ionic, surfactant complexer. In more detail, the compositions and concentrates for use of the two-component complexer of the invention are formulated with from about 0.5 to about 4 p of polyvinylpyrrolidone per available iodine p and more preferably from about 0.5 to about 2.5 p of PVP. Correspondingly, the level of surfactant complexing is widely in the range of from about 0.5 to about 4 p per pof available iodine, and more preferably from about 0.5 to about 3.5 p, and still more preferably from 2 to about 3.5 p. The PVP fraction of the two-component complexer must have a molecular weight of from approximately 8,000 to approximately 1,300,000, which include commercially available materials designated as K-17, K-30, K-60 and K-90. PVP K-30 is the most preferred member of this class. The surfactant complexing fraction of the two-component complexing agent is preferably selected from the group containing the polyethoxylated polyoxypropylene, alkylphenol ethoxylates (for example nonoxinoles) and ethoxylated fatty alcohols and fatty acids. Polyethoxylated polyoxypropylenes are the most preferred surfactant, and the poloxamers described above in connection with the first aspect of the invention are likewise the most preferred surfactants for use in two-component complexing agents. Nonoxynol 10 and 15 are especially preferred surfactants. The ethoxylated fatty alcohol surfactants include the surfactants Pareth-25-9 and Pareth-25-12 (ethoxylated fatty alcohols of 12 to 15 carbon atoms). The pH of the two-component complexing agent compositions is typically in the range of from 2 to about 7, more preferably from about 2 to about 6.5, and more preferably from about 4 to about 6.5. In the case of the corresponding concentrates, the preferred pH is in the range of about 3 to about 6.5.

The two-component complexing compositions and concentrates also include the iodide ion, generally used at a level of about 0.2 to 1 pof iodide ion per pof available iodine, and more preferably from about 0.3 to 0.5 pof iodide ion. In addition, the compositions and concentrates according to this aspect of the invention may include buffering agents (eg, citric, lactic, acetic and phosphoric acid salts, and mixtures thereof); emollients (e.g., glycerin, sorbitol, propylene glycol, lanolin, ethoxylated lanolin derivatives and mixtures thereof) at a level of from about 0.1% to 15% by weight in the use compositions (more preferably about 1-5%) and up to about 32% by weight (more preferably from about 0.5% to about 50% by weight in the concentrates); and other various optional ingredients.

Detailed Description of the Preferred Modalities Preferred poloxamers, useful in many aspects of the invention, can be derived from any commercial source. However, the appropriate "pluronic" poloxamers marketed by BASF Chemical Co. have been found to be particularly suitable, as long as the members of this family are selected having the required molecular weight of polyoxypropylene (POP molecular weight) and polyoxyethylene content ( molecular weight of POE). The pluronic poloxamers are described in a BASF booklet entitled "Typical Properties of Block Copolymer Surfactants", such a booklet being incorporated by reference herein. It should be understood in this regard that poloxamers having a POP molecular weight above about 4500 are not currently available, but such species could be expected to be useful in the context of the present invention. Not every member of the defined class of the poloxamers of the present invention is necessarily suitable for any low ratio of poloxamer to the average available iodine, at any level of iodine. Generally speaking, with the compositions for final use, a somewhat higher ratio of the poloxamer to the available iodine average available at 0.1% level is available, compared to the minimum proportions required at the highest available iodine levels. However, all members of this defined class that have already been studied can be used in a certain proportion, at about 4.5: 1 or less. Finally, other types of complexing agents can be used in combination with one or more members of the defined class of poloxamers. For example, complexing agents such as alcohol ethoxylates, nonylphenol ethoxylates, and polyvinylpyrrolidone can be used in conjunction with defined poloxamers, particularly where the latter are present as the main complexing component. In addition, it will be understood that most detergent-iodine compositions formulated for application to the skin may contain a minimum of about 0.1% available iodine and a maximum of about 1.3% available, and usually this maximum may be considered as in the order of about 1% available iodine. There are iodine-detergent compositions, which have nominal iodine values available, but in fact they contain significantly more average available iodine. For example, a product with available iodine nominal of 1%, can in fact contain as much as 1.2% or even 1.25% by weight of available iodine. This occurs because many compositions will contain a significant "surplus" of iodine available when they are manufactured, to allow the loss of iodine in the life of the product. As such, it will be understood that the reference herein to the average available iodine on a nominal basis covers such excess amounts. The compositions of the invention will also contain iodide which can usually vary depending on the formulation, from about 0.2-1 part of iodide ion to part of average available iodine. However, the novel compositions of the invention are not dependent on iodide as far as the amount of iodide in question is concerned. The amount of iodide present can in some cases have an effect on the stability and homogeneity of a given composition of use. However, the new proportions of the complexer: iodine can accommodate the iodide levels previously used in the technique. The presence of buffering agent (s) is generally desirable in the compositions and in the concentrates according to the present invention, and those salts previously described are preferred. Sodium citrate is the most preferred buffering agent. The amount of buffering agent employed in a particular formulation is chosen based on the stability characteristics of pH determined over a period of time. In the compositions of use, the small amount of buffering agent present has little or no effect on the homogeneity and stability of the product. In the concentratesHowever, where damping agents are present at high levels and the water content is significantly lower, the choice of the damping agent can make a significant difference. The compositions of the invention may also include viscosity agents commonly employed in the above formulations. Here again, the selection and the amount of such agent (s) is dependent on the particular characteristics desired for a given formulation, and it does not matter whether the composition is in diluted form for the final use, or it is sold as a concentrate. The compositions of the invention may also include small amounts of solvents such as alcohols and glycols, which may function to modify the viscosity and to aid in the preparation of the concentrate.

The following examples describe certain preferred compositions and concentrates according to the first aspect of the invention, as well as the methods for the preparation and the stability test of those formulations. It should be understood that the examples are provided by way of illustration only, and nothing herein should be taken as a limitation on the full scope of the invention.

Example 1 A series of aqueous detergent-iodine compositions according to the invention were prepared, each including 4.5% by weight of a poloxamer, an available average iodine content of about 1% (whereby a poloxamer: iodine ratio is given) available from 4.5). 0.4% by weight of iodide, 2.0% by weight of glycerin, and 0.5% by weight of sodium citrate buffer, to give an adjusted pH of about 5. The rest of the compositions consisted of water. In some samples, the poloxamer used had appropriate molecular weight values and polyoxyethylene percentage according to the invention, and in other samples, different types of poloxamers were used.

Each sample was prepared by mixing an appropriate commercial Pluronic poloxamer (or a mixture of commercial grades to achieve intermediate-value poloxamers) with an aqueous iodine concentrate containing approximately 57% by weight of iodine and 20% by weight of iodide as sodium iodide. A small amount of water was then added, followed by the glycerin and the sodium citrate buffer. After a small amount of mixing, the amount of water remaining in the formula was added. After the formulation, the homogeneity of the compositions was observed at room temperature, and portions of each sample were tested for high and low temperature stability. Specifically, in the low temperature stability test, the respective samples were placed in a refrigerator at 2 ° C for one week, and a high temperature test, the samples were placed in a constant temperature oven at 40 ° C. At the end of the test week, test samples at low and high temperature were observed for precipitation and turbidity; those that showed undue turbidity or precipitation were rejected. The following Table 1 describes the molecular weight of the poloxamer and the percentage of polyoxyethylene for the test samples, as well as the results of the stability tests, where "O.K." represents an acceptable product and "X" represents an unacceptable product.

Table 1 POP molecular weight = average molecular weight of the central polyoxypropylene group of poloxamer block copolymer. 1% POE = average polyoxyethylene content of the poloxamer block copolymer based on total weight of the copolymer, eg, 50% = about 50% by weight of the total poloxamer constitutes POE.

The above data demonstrate that an average POP molecular weight of the order of about 2500 to about 4000, together with a POE content of about 25% -75% by weight, is important in obtaining a stable product having a of poloxamer: relatively low available iodine.

Example 2 In another similar test series, aqueous detergent-iodine compositions having varying compositions with different levels of poloxamer, emollient, and pH were prepared, and the stability tests described above were performed. Each sample contained an appropriate poloxamer, an average available iodine content of about 1.0% and 0.5% by weight of sodium citrate buffer; the samples were made by the steps described in Example 1, and the rest of each composition was water. The results of these tests are described in Table 2.

Table 2 IV) This example demonstrates that the content of emollient, iodide and pH levels can be varied at wide ranges, while still providing acceptable compositions having low detergent-iodine ratios.

Example 3 In this test a number of aqueous detergent-iodine compositions were prepared and stability was tested as described in Example 1. In each case, the poloxamer had a POP molecular weight of 3200, and a POE content of 50% (except sample # 2 which had a POE content of 40%); all had an average available iodine content of 0.5% by weight, an iodide content of 0.2% by weight, a sodium citrate content of 0.25% by weight, and a pH of approximately 5. The amounts of poloxamer and glycerin they were varied, but in all cases, the balance of the respective compositions was made up of water. These results are described below.

Table 3 Example _4 An additional series of compositions were prepared and tested for stability, using various commercial grade Poloxamers (or mixtures thereof), at different levels with an iodine content of about 0.25% by weight, 0.2% by weight of buffer. sodium citrate and with a pH of about 5. The compositions were made and tested as in Example 1 and the rest of each composition was water. The data from this series of tests are described in Table 4.

Table 4 IV Example 5 In this example, a series of low proportion detergent / iodine poloxamer aqueous compositions of pH = 5 containing 0.25% by weight of average available iodine and 0.2% by weight of citrate buffer were prepared and tested for stability. of sodium, as described in Example 1; the rest of all the compositions was water. The results are described in the following table, and should be compared with the results in Table 4.

Table 5 u > As described above, compositions with available iodine of about 0.25% having POP molecular weights of less than about 2600 were unsatisfactory, whereas those compositions described in Table 4 made with POP portions of higher molecular weight were stable. .

Example 6 A further series of compositions were prepared, all having 0.45% by weight of poloxamer, an available iodine content of about 0.1% by weight, an iodine content of about 0.4% by weight and a pH of about 5. These compositions were made and were tested as described in Example 1, with the remainder of each composition being water.

Table 6 Example 7 A series of aqueous detergent / iodine compositions were made using a number of different Poloxamers, all having POP molecular weights below 2600. In all cases 0.45% by weight of Poloxamer was used, and the compositions contained approximately 0.1% by weight. available iodine weight, 0.04% by weight of iodide, 0.2% by weight of glycerin and 0.05% by weight of sodium citrate; all compositions had a pH of 5. All compositions were unstable either at room temperature and at colder temperatures. In this series of compositions, poloxamers having the following POP molecular weight distributions / POE percentage: 1300/40%; 1700/20%; 1700/40%; 1700/50%; 1700/80%; 2100/50%; 2300/40%; and 2300/70%.

Example 8 As previously described, the iodine concentration of the following iodine compositions adapted to topical application to the skin, is predominantly in the range of about 0.1% -1% of average available iodine. It is often desired to prepare concentrations of such compositions, suitable for dilution before use. Total concentrates offer the advantages of minimizing manufacturing, packaging, shipping and storage costs. The detergent-iodine compositions of the invention are particularly suitable for such concentrates, since they use a minimum of total solids in the concentrate and therefore maximize the amount of water that may be present. Without enough water, many concentrates are excessively viscous, and it can be difficult to provide adequate buffering. Generally speaking, the concentrates usually contain about 1% -5% by weight of available iodine, and are usually formulated to provide 4, 8 and 16 times the volume of the original concentrate, after dilution with an appropriate amount of water. A composition adapted for dilution with 3 parts of water, to produce a level of 1% available iodine, can be formulated using a Poloxamer having a proportion of% mol POP /% POE by weight of 3200/50% at a level of 12%; 4.3% by weight of average available iodine; an iodide content of 1.5% by weight and a content of citrate buffer of pH 3 of 0.5% by weight. These compositions are formulated as described in Example 1. Yet another composition for use at the same 1 + 3 dilution factor, to produce the available iodine level at nominal 1%, can be formulated using a poloxamer having a value printed POP / POE of% by weight of 3200/54% at a level of 16%; 4. 1% by weight of average available iodine; an iodine content of 1.4% by weight; 19% by weight of glycerin; and a 0.5% by weight citrate buffer content of pH 5. The rest of this composition is water. The following compositions shown below can be diluted with 7 and 15 parts of water to produce 0.1% average available iodine. The compositions are prepared as described in the Example 1, and the rest of them in each case is water.

Table 7 00 As can be seen from the previous examples, the present invention provides improved compositions and concentrates for the use of iodine germicide with poloxamer, of variant constitution. The following tables respectively for the compositions of use concentrates describe the types of ingredients contemplated in connection with the first aspect of the invention, as well as the approximate ranges and preferred levels of use thereof. Table 8 Compositions of Use Sufficient amount to bring the total to 100% Table 9 Concentrates Sufficient amount to bring the total to 100%.

The following examples describe various iodine complexing compositions that include two-component complexing agents that contain Povidone and non-ionic surfactant. It should be understood that these examples are provided by way of illustration only, and nothing in these should be taken as a limitation on the full scope of the invention. In these examples, various commercial designations are employed for some of the ingredients, for example, Poloxamer, Povidone, Nonoxynol and Pareth, with the subsequent identification numbers. These identifications are well known in the art, and additional information can be obtained from various standard techniques, such as the CTFA Cosmetic Ingredient Dictionary.

Example 9 A series of aqueous combinations of Povidone K-30 and a surfactant, non-ionic complex former were prepared. The proportion of the Povidone to available iodine (triturable thiosulfate) was in the range of 0.5: 1 to 1.5: 1, the ratio of nonionic surfactant (Poloxamer 335) to available iodine was in the range of 1.5: 1 to 0.5: 1. The samples were first prepared by dissolving the required amount of the nonionic surfactant complexer at or about 50% of the required amount of water, followed by the stirring addition of an aqueous iodine concentrate containing about 57% by weight of iodine and 24% by weight of sodium iodide. The required amount of Povidone powder was then added, with stirring. The emollient, glycerin, was then added followed by citric acid and the appropriate amount of sodium hydroxide solution, to reach the desired pH level. The amount of water remaining in the formula was then added, with agitation. Finally, the preparations were filtered.

Table 10 Example 10 A series of aqueous compositions containing Povidone, non-ionic surfactants and iodine were prepared with proportions of Povidone: iodine of 2.5: 1 and nonionic surfactant: iodine of 2: 1. All compositions were tested for homogeneity / stability for at least one week at 2 ° C (refrigerator) and at 40 ° C in a constant temperature oven; any compositions showing undue turbidity or precipitation were rejected. However, all the compositions of Table 2 were satisfactory.

Table 11 Similar compositions were prepared using Povidone with K-values of 17.60 and 90, and gave homogeneous products. Substantially all the aqueous dilutions of these compositions gave homogeneous final products that were not cloudy and did not separate. The approximate average molecular weights for Povidone with K values of 17, 30, 60 and 90 are 9,000; 42,000; 200,000; and 1,100, 000, respectively. In a similar manner, the compositions of 13-22 were prepared as described above, using all the ingredients of Table 11, except that Poloxamer 235 was used, and Poloxamer 334 was used in place of Poloxamer 335. However, the amount The total non-ionic surfactant complexing used in each case was 0.5% by weight, instead of the 2% level of Table 11. Compositions 13-22 were also stable at high and low temperatures. Variants of compositions 13-22 were also prepared using Povidone with K values of 17, 60 and 90. These variants also gave homogeneous products, and their aqueous dilutions generally gave homogeneous solutions which were not cloudy and did not separate.

Example 11 A series of compositions containing 2.5% Povidone of different K values was prepared, together with a non-ionic surfactant co-complexer and glycerin emollient. The ingredients of these compositions are described in Table 12. The iodide levels of the compositions were approximately 0.4% by weight.

Table 12 Example 12 A series of compositions containing 2% Povidone K-30 was prepared either together with 0.5% or 1% by weight co-complexing non-ionic surfactant. All compositions contained citrate buffer and an iodide content of about 0.4-0.5 parts per part of available iodine, along with some glycerin. The following are examples of homogeneous compositions. Table 13 Example 13 In this example, compositions 38 and 39 were prepared each containing in weight percent: 1% in Povidone K30; 1% available iodine; 2% glycerin; 0.2% citric acid; and water up to 100%. The compositions each had a pH of about and differed in the nonionic surfactant complexing used. In the case of composition 38, it was used Poloxamer 335 at a level of 1.5%, while in composition 39, Poloxamer 403 was used at that same level. At these proportions of complexer, the use of poloxamers having a central hydrophobic portion of a molecular weight greater than about 3,000 Example 14 In this example, additional compositions Nos. 40 and 41 were prepared with 1% iodine using 0.5% Povidone K-30 (ratio 0.5: 1) in combination with 4% non-ionic surfactant co-complexer (ratio 4). : 1) based on the Poloxamers having a molecular weight of the central portion of about 3,000 or more, together with an ethylene oxide content of about 30-50%. At a 4: 1 ratio of non-ionic surfactant co-complexer to iodine, these Poloxamers worked better than most other non-ionic surfactants.

Each of the compositions of this example contained (% by weight): Povidone K-30, 0.5%; available iodine, 1%; glycerin, 2%; citric acid, 0.1%; and water, up to 100%. Each of the compositions had a pH of about 5. In the case of composition 40, 4% of Poloxamer 335 was used, while in composition 41, the same level of Poloxamer 403 was used.

Example 15 Two bovine bovine baths were prepared according to the present invention. These baths had an available iodine content of approximately 0.15% and relatively high levels of emollient (glycerin and sorbitol). At such low iodine contents and high contents of organic emollient, the stability of the iodine can be maintained through the use of the iodate technology described in US Pat. No. 4,271,149, which is incorporated herein by reference. In such baths or teats, it is customary to employ a viscosity agent to thicken the product, so that it does not drip too quickly. Also the use of a small amount of effective wetting agent can further assist in uniform diffusion and adhesion.

Each of late compositions for rinsing or bathing of tits 42 and 43 contained the following ingredients (% by weight): Povidone K30, 0.3%; iodine available 0.15%; glycerin, 2%; 3% sorbitol 70%; citric acid, 0.1%; xanthan gum thickener, 0.1%; dioctyl-sodium sulfosuccinate, 0.04%; sodium iodate, 0.12%; and water up to 100%. The compositions had a pH of 5-6. The composition 42 for rinsing or bathing tits contained 0.375% Poloxamer 403, and composition 43 contained the same amount of Pareth-25-12. The compositions made according to this example provide a free (non-complexed) iodine content in the range of about 5-10 ppm, resulting in very rapid germicidal activity. The xanthan gum provides a viscosity of about 30 cps, resulting in good adhesion. The total emollient content of 4% provides excellent conditioning characteristics of the skin, considering that it represents more than 80% of the total content of solid ingredients.

Example 16 A series of iodine compositions containing Povidone K-30 and various non-ionic surfactant complexers were prepared, in which the total proportion of complex: iodine was 2.5: 1. These compositions were prepared as described in Example 9, with some of the compositions containing additional ingredients to modify the viscosity and wetting characteristics. The ingredients of these compositions are described below.

Table 14 ro continuation Table 14 in or Concentrations of 0.5% and 0.25% of available average iodine, many stable compositions with similar proportions of ingredients can be prepared. At 0.1% available average iodine, some stable compositions can be elaborated, with similar proportions.

Example 17 In this example, a dilidable concentrated composition was prepared. Such concentrates are provided at iodine levels greater than 1%, so that after dilution with water, a finished product with 1% or less of iodine (below about 0.05%) results. Not all formulations can be concentrated appreciably, due to viscosity and homogeneity considerations, but a representative concentrate according to the invention contains (% by weight): Povidone K-30, 6.0%; available iodine, 3%; Poloxamer 335, 3%; glycerin, 6%; citric acid, 0.25%; and water up to 100%. This concentrate has a pH of about 5-6, and can be diluted in water to form a stable composition having an available iodine content of about 1%.

As can be seen from the above examples, the present invention provides stable, improved detergent-iodine use compositions and concentrates characterized by complex two-component formation systems. The following tables, respectively for such compositions and concentrates of use, describe the types of ingredients contemplated, as well as the appropriate ranges and preferred levels of use thereof.

Table 15 Use Regulations that Contain Si Complex Complex Formers or Two-Component Complexes *. Enough enough to bring the total to 100%.

Table 16 Concentrates that Contain Two-component Complementary Systems Enough quantity to bring the total to 100%.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, the content of the following is claimed as property:

Claims (43)

1. An aqueous germicidal complex-iodine-forming composition, characterized in that it comprises an average amount of available iodine in a nominal base, and from about 2 to about 4.5 parts of complexing or complexing agent per part of average available iodine, including agent of complex ation individual amounts of polyvinylpyrrolidone and a compatible nonionic surfactant complexer.

2. The composition according to claim 1, characterized in that the available iodine is present at a level from about 0.1% to about 1.3% by weight of available iodine in a nominal base.

3. The composition according to claim 1, characterized in that the polyvinylpyrrolidone is present at a level from about 0.5 to about 4 parts per part of available iodine.

4. The composition according to claim 3, characterized in that the level is from about 0.5 to about 2.5 parts.

5. The composition according to claim 1, characterized in that the surfactant complexing agent is selected from the group consisting of polyethoxylated polyethoxylates, alkylphenol ethoxylates and ethoxylated fatty alcohol and acidic surfactants and mixtures thereof.

6. The composition according to claim 5, characterized in that the surfactant complexer is a polyethoxylated polyoxypropylene having an average molecular weight of polyoxypropylene and an average polyoxyethylene content, said average molecular weight of polyoxypropylene being up to about 4500.

7. The composition according to claim 6, characterized in that the average molecular weight of the polyoxypropylene is from about 2600 to about 4000.

8. The composition according to claim 7, characterized in that the average molecular weight of the polyoxypropylene is from about 3000 to about 4000.

9. The composition according to claim 6, characterized in that the average content of the polyoxyethylene is from about 30% to about 75% by weight.

10. The composition according to claim 9, characterized in that the average polyoxyethylene content is from about 30% to about 50% by weight.

11. The composition according to claim 1, characterized in that the composition has a pH of from about 2 to about 7.

12. The composition according to claim 11, characterized in that the pH is from about 3 to about 6.5.

13. The composition according to claim 11, characterized in that the pH is from about 4 to about 6.5.

14. The composition according to claim 1, characterized in that the surfactant complexing is present at a level of from about 0.5 to about 4 parts of surfactant complexing by available iodine.

15. The composition according to claim 14, characterized in that the level is from about 0.5 to about 3.5 parts.

16. The composition according to claim 1, characterized in that it includes from about 0.2 to about 1 part of iodide ion per part of available iodine.

17. The composition according to claim 16, characterized in that it includes from about 0.3 to about 0.5 parts of iodide ion per part of available iodine.

18. The composition according to claim 1, characterized in that it includes a buffering agent.

19. The composition according to claim 18, characterized in that the buffering agent is selected from the group consisting of salts of the citric, lactic, acetic and phosphoric acids, and mixtures thereof.

20. The composition according to claim 1, characterized in that it includes an amount of emollient therein.

21. The composition according to claim 20, characterized in that the emollient is present at a level from about 0.1% to about 15% by weight.

22. The composition according to claim 20, characterized in that the emollient is selected from the group consisting of glycerin, sorbitol, propylene glycol, lanolin, ethoxylated lanolin derivatives, and mixtures thereof.

23. An aqueous, stylo-iodine complex germicidal concentrate, adapted for dilution with water to form a stable use composition, said concentrate is characterized in that it comprises from about 1% to about 5% by weight of average available iodine in a nominal base, and from about 2 to about 4.5 parts of complexing agent per part of available iodine, said complexing agent includes individual amounts of polyvinyl pyrrolidone and a compatible nonionic surfactant complexer.

24. The concentrate according to claim 23, characterized in that the polyvinylpyrrolidone is present at a level of about 0.5 to about 4 parts per part of available iodine.

25. The concentrate according to claim 24, characterized in that the level is from about 0.5 to about 2.5 parts.

26. The concentrate according to claim 23, characterized in that the surfactant complexer is selected from the group consisting of polyethoxylated polyoxypropylenes, alkylphenol ethoxylates and ethoxylated fatty alcohol and fatty acid surfactants, and mixtures thereof.

27. The concentrate according to claim 26, characterized in that the surfactant is a polyethoxylated polyoxypropylene having an average molecular weight of polyoxypropylene and an average polyoxyethylene content, said average molecular weight of the polyoxypropylene is up to about 4500.

28. The concentrate according to claim 27, characterized in that the average molecular weight of the polyoxypropylene is from about 2600 to about 4000.

29. The concentrate according to claim 28, characterized in that the average molecular weight of the polyoxypropylene is from about 3000 to about 4000.

30. The concentrate according to claim 27, characterized in that the average polyoxyethylene content is from about 30% to about 75% by weight.

31. The concentrate according to claim 30, characterized in that the average polyoxyethylene content is from about 30% to about 50% by weight.

32. The concentrate according to claim 23, characterized in that the concentrate has a pH from about 2 to about 7.

33. The concentrate according to claim 32, characterized in that the pH is from about 3 to about 6.5.

34. The concentrate according to claim 32, characterized in that the pH is from about 4 to about 6.5

35. The concentrate according to claim 23, characterized in that the surfactant complexing is present at a level of from about 0.5 to about 4 parts of surfactant complexing by available iodine.

36. The concentrate according to claim 35, characterized in that the level is from about 0.5 to about 3.5 parts.

37. The concentrate according to claim 23, characterized in that it includes from about 0.2 to about 1 part of iodide ion per part of available iodine.

38. The concentrate according to claim 37, characterized in that it includes from 0.3 to 0.5 parts of iodide ion per part of available iodine.

39. The concentrate according to claim 23, characterized in that it includes a buffering agent.

40. The concentrate according to claim 39, characterized in that the buffering agent is selected from the group consisting of the salts of the citric, lactic, acetic and phosphoric acids and mixtures thereof.

41. The concentrate according to claim 23, characterized in that it includes an amount of emollient therein.

42. The concentrate according to claim 41, characterized in that the emollient is present at a level of from about 0.5% to about 50% by weight.

43. The concentrate according to claim 41, characterized in that the emollient is selected from the group consisting of glycerin, sorbitol, propylene glycol, lanolin, ethoxylated lanolin derivatives, and mixtures thereof. SUMMARY OF THE INVENTION Compositions and concentrates for use, germicidal, iodine compiejo-forming, aqueous, stable, adapted for application to human or animal skin, which have desirable proportions, are described. The complex or complexing agent: iodine from about 2 -4.5. The compositions and concentrates preferably having a polyethoxylated polyoxypropylene block copolymer (Poloxamer) as the complexing agent, wherein the polyoxypropylene portion has an average molecular weight of at least 2600 and a polyoxyethylene content of about 30% -75% by weight, in combinations with from about 0.1% - 5% by weight of average available iodine on a nominal basis. The use of the defined class of the poloxamers allows the formulation of stable compositions and concentrates at low and high temperature. Other ingredients such as emollients, buffers and viscosity improvers may also be part of the compositions and concentrates of use. In yet another aspect of the invention, the compositions and concentrates of complexed-iodine include two-component complexing systems that include individual amounts of polyvinylpyrrolidone and a non-ionic surfactant such as a Poloxamer.