The use of compounds of the formula I

The invention relates to the use of bicyclic and tricyclic enamines which carry electron-withdrawing substituents on the -ene double bond as light protection agents in cosmetic and pharmaceutical preparations and as light protection additives (light stabilizers) in plastics. The invention further relates to novel compounds of said type which have a light protection action.
The light protection agents used in cosmetic and pharmaceutical preparations have the task of preventing, or at least diminishing the consequences of, harmful effects of sunlight on the human skin. However, these light protection agents also serve to protect other ingredients from decomposition or breakdown by UV radiation. In hair cosmetic formulations, the aim is to reduce damage to the keratin fibers by UV rays.
The sunlight reaching the surface of the earth contains UV-B radiation (280 to 320 nm) and UV-A radiation ( greater than 320 nm), which are directly adjacent to the visible light region. The effect on the human skin is manifested, particularly in the case of UV-B radiation, by sunburn. Accordingly, the industry offers a relatively large number of substances which absorb UV-B radiation and thus prevent sunburn.
Dermatological investigations have now shown that UV-A radiation is also perfectly capable of causing skin damage and allergies by, for example, damaging the keratin or elastin. This reduces the elasticity and water storage capacity of the skin, i.e. the skin becomes less supple and tends to form wrinkles. The noticeably high incidence of skin cancers in areas of strong solar radiation shows that damage to the genetic information in the cells is evidently also caused by sunlight, specifically by UV-A radiation. All these findings would therefore suggest that it is necessary to develop efficient filter substances for the UV-A region.
There is a growing demand for light protection agents for cosmetic and pharmaceutical preparations which can be used in particular as UV-A filters and whose absorption maxima ought therefore to be in the range from about 320 to 380 nm. In order to achieve the desired effect using the minimum amount, light protection agents of this type should additionally have a high specific absorbance. Light protection agents for cosmetic preparations must also meet a large number of other requirements, for example good solubility in cosmetic oils, high stability of the emulsions prepared therewith, toxicological acceptability and low intrinsic odor and low intrinsic color.
Another requirement which light protection agents must meet is adequate photostability. However, this requirement is met only inadequately, if at all, by the UV-A-absorbing light protection agents available hitherto.
French Patent No. 2 440 933 describes 4-(1,1-dimethylethyl)-4xe2x80x2-methoxydibenzoylmethane as a UV-A filter. It is proposed to combine this particular UV-A filter, which is sold by GIVAUDAN under the name xe2x80x9cPARSOL 1789xe2x80x9d, with various UV-B filters in order to absorb all UV rays having a wavelength from 280 to 380 nm.
However, this UV-A filter does not have sufficient photochemical stability, when used alone or in combination with UV-B filters, to ensure sustained protection of the skin during sunbathing for extended periods, which means that repeated applications at regular and short intervals are required if effective protection of the skin from all UV rays is desired.
For this reason, EP-A-0 514 491 discloses the stabilization of the insufficiently photostable UV-A filters by adding 2-cyano-3,3-diphenylacrylic esters, which themselves act as filters in the UV-B region.
Furthermore, it has already been proposed in EP-A-0 251 398 to combine chromophores which absorb UV-A radiation and UV-B radiation into a molecule via a linker. This has the disadvantage that firstly it is no longer possible to freely combine UV-A and UV-B filters in the cosmetic preparation, and that difficulties in the chemical linkage of the chromophores permit only certain combinations.
U.S. Pat. No. 4,950,467 describes the use of 2,4-pentadienoic acid derivatives as UV absorbers in cosmetic preparations. The monoaryl-substituted compounds specified in this patent specification as being preferable likewise have the disadvantage that their photostability is insufficient.
It is an object of the present invention to propose light protection agents for cosmetic and pharmaceutical purposes which absorb predominantly in the UV-A region (and optionally alternatively in the UV-B region) with high absorbance, are photostable, have low intrinsic color, i.e. a sharp band structure, and are soluble in oil or water depending on the substituent.
We have found that this object is achieved according to the invention by the use of compounds of the formula I
in which
R1 and R2 are identical or different, electron-withdrawing radicals chosen from the group consisting of cyano, alkyl- or arylcarbonyl, alkyloxy- or aryloxycarbonyl and optionally substituted aminocarbonyl,
R3 is a hydrogen atom, a C1-C20-alkyl radical or a C3-C20-cycloalkyl radical or a radical of the formula xe2x80x94CH2xe2x80x94CH2xe2x80x94SO3xe2x80x94M+, where M+ is a cation,
X is the divalent radical of oxygen, sulfur or the radical
where R3 is as defined above,
Z is the divalent radical of the formula II or III, which forms a fused system with the radical of the formula I
where R4 can be bonded one or more times to the benzylidene ring I or naphthylidene ring II, and is hydrogen, alkyl, cycloalkyl, alkyloxy, cycloalkyloxy, alkoxycarbonyl, mono- or dialkylaminocarbonyl, alkylamino, dialkylamino, each having up to 20 carbon atoms, and also cyano, amino and SO3xe2x80x94M+, where M+ is a metal cation,
as photostable UV filters in cosmetic and pharmaceutical preparations to protect human skin and human hair against solar rays, alone or together with compounds which absorb in the UV region and are known per se for cosmetic and pharmaceutical preparations.
Preferred compounds are those in which Z is the radical of the formula II.
With regard to the substituents, preference is given to compounds in which R1 is cyano or alkyloxycarbonyl having from 2 to 12 carbon atoms, R2 is hydrogen, R3 is hydrogen or methyl, and R4 is C1-C8-alkyl, C1-C8-alkoxy or SO3xe2x80x94M+, where M+ is a cation chosen from the group consisting of
where R5, R6 and R7 are hydrogen or low molecular weight alkyl or hydroxyalkyl, and metal cations.
The alkyl radicals in the substituents R1 to R4 preferably have from 1 to 8 carbon atoms and are, in particular, low molecular weight alkyl radicals having from 1 to 5 carbon atoms and, preferably, methyl radicals.
The alkyl radicals in the substituents R4 are isocyclic or heterocyclic radicals having from 5 to 10 ring atoms and from 3 to 5 carbon atoms which can be further substituted.
In the radicals xe2x80x94SO3xe2x80x94M+ and xe2x80x94CH2xe2x80x94CH2xe2x80x94SO3xe2x80x94M+, M+ is usually an alkali metal, alkaline earth metal or ammonium cation, in particular Na+, K+, NH4+, +NH(C2H5)3 and +NH(xe2x80x94CH2xe2x80x94H2OH)3. Generally speaking, only cations which are physiologically compatible at the use concentrations are suitable.
Of the compounds of the formula I, the compounds of the formula IV are novel
in which R1, R2, R3 and R4 are as defined above.
Equally novel are the compounds of the formula V
in which X is the divalent radical of oxygen, sulfur or the radical
and R1 and R2 independently of one another are CN or alkoxycarbonyl having from 2 to 10 carbon atoms which can be substituted by a radical xe2x80x94(CH2)nxe2x80x94SO3xe2x80x94M+, R3 is hydrogen, methyl or xe2x80x94(CH2)nxe2x80x94SO3xe2x80x94M+, and R4 is hydrogen or one or more identical or different radicals C1- to C8-alkyl, C1- to C8-alkoxy or the radical xe2x80x94SO3xe2x80x94M+, where in each case n is the number 2 or 3 and M+ is a cation chosen from the group consisting of
in which R5, R6 and R7 are hydrogen or low molecular weight alkyl or hydroxyalkyl, and metal cations,
with the proviso that the compound of the formula V has at least one radical xe2x80x94(CH2)nSO3xe2x80x94M+ or xe2x80x94SO3xe2x80x94M+.
The compounds of the formula I are obtained in a manner known per se, as is described, for example, in CH 601984, by reacting a compound of the formula VI
compound of the formula VII
in which R1 to R3 are as defined above, and R is a low molecular weight alkyl radical, preferably methyl.
Using the compound
as an example, this may be exemplified by the following reaction equation.
The reaction is carried out by heating to relatively high temperatures, e.g. to from 20 to 150xc2x0 C., preferably from 50 to 1200xc2x0 C. and in particular from 70 to 100xc2x0 C.
The present invention further relates to cosmetic and pharmaceutical preparations which comprise from 0.1 to 10% by weight, preferably from 1 to 7% by weight, based on the total amount of the cosmetic and pharmaceutical preparation, of one or more of the compounds of the formula I together with compounds which absorb in the UV-A and UV-B region and are known per se for cosmetic and pharmaceutical preparations as light protection agents, where the compounds of the formula I are generally used in a lesser amount than the UV-B-absorbing compounds.
The cosmetic and pharmaceutical preparations which comprise light protection agents are usually based on a carrier which comprises at least one oil phase. However, preparations merely based on water are also possible if compounds with hydrophilic substituents are used. Accordingly, suitable preparations are oils, oil-in-water and water-in-oil emulsions, creams and pastes, lipcare stick compositions or grease-free gels.
Sunscreen preparations of this type can, accordingly, be in liquid, paste or solid form, for example as water-in-oil creams, oil-in-water creams and lotions, aerosol foam creams, gels, oils, wax pencils, powders, sprays or alcoholic-aqueous lotions.
Other suitable emulsions are, inter alia, O/W macroemulsions, O/W microemulsions or O/W/O emulsions with compounds of the formula I in dispersed form, where the emulsions are obtainable by phase inversion technology, as in DE-A-197 26 121.
Customary cosmetic auxiliaries which may be suitable as additives are, for example, coemulsifiers, fats and waxes, stabilizers, thickeners, biogenic active ingredients, film formers, fragrances, dyes, pearlizing agents, preservatives, pigments, electrolytes (e.g. magnesium sulfate) and pH regulators. Suitable coemulsifiers are preferably known W/O and also O/W emulsifiers such as, for example, polyglycerol esters, sorbitan esters or partially esterified glycerides. Typical examples of fats are glycerides; waxes which may be mentioned are, inter alia, beeswax, paraffin wax or microwaxes, possibly in combination with hydrophilic waxes. Stabilizers which can be used are metal salts of fatty acids such as, for example, magnesium, aluminum and/or zinc stearate. Suitable thickeners are, for example, crosslinked polyacrylic acids and derivatives thereof, polysaccharides, in particular xanthan gum, guar guar, agar agar, alginates and tyloses, carboxylmethylcellulose and hydroxyethylcellulose and also fatty alcohols, monoglycerides and fatty acids, polyacrylates, polyvinyl alcohol and polyvinylpyrrolidone. Examples of biogenic active ingredients are plant extracts, protein hydrolysates and vitamin complexes. Examples of customary film formers are hydrocolloids such as chitosan, microcrystalline chitosan or quaternized chitosan, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, polymers of the acrylic acid series, quaternary cellulose derivatives and similar compounds. Examples of suitable preservatives are formaldehyde solution, p-hydroxybenzoate or sorbic acid. Examples of pearlizing agents are glycol distearic esters such as ethylene glycol distearate, but also fatty acids and fatty acid monoglycol esters. Dyes which can be used are the substances suitable and approved for cosmetic purposes, as listed, for example, in the publication xe2x80x9cKosmetische Farbemittelxe2x80x9d [Cosmetic Colorants] from the Farbstoffkommission der Deutschen Forschungsgemeinschaft, [Dyes Commission of the German Research Society], published in Verlag Chemie, Weinheim, 1984. These dyes are normally used in concentrations of from 0.001 to 0.1% by weight, based on the total mixture.
An additional content of antioxidants is generally preferred. Thus, favorable antioxidants which can be used are all antioxidants which are customary or suitable for cosmetic and/or dermatological applications.
The antioxidants are advantageously chosen from the group consisting of amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazoles (e.g. urocanic acid) and derivatives thereof, peptides such as D,L-carnosine, D-carnosine, L-carnosine and derivatives thereof (e.g. anserine), carotenoides, carotenes (e.g. xcex2-carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, lipoic acid and derivatives thereof (e.g. dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (e.g. thiorodoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl, and lauryl, palmitoyl, oleyl, xcex3-linoleyl, cholesteryl and glyceryl esters thereof) and also salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts), and sulfoximine compounds (e.g. buthionine sulfoximines, homocysteine sulfoximines, buthionine sulfones, penta-, hexa-, heptathionine sulfoximine) in very low tolerated doses (e.g. pmol to xcexcmol/kg), and also (metal) chelating agents (e.g. xcex1-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), xcex1-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, biliburin, biliverdin, EDTA and derivatives thereof, unsaturated fatty acids and derivatives thereof (e.g. xcex3-linolenic acid, linoleic acid, oleic acid), folic acid and derivatives thereof, ubiquinone and ubiquinole and derivatives thereof, vitamin C and derivatives thereof (e.g. ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherol and derivatives (e.g. vitamin E acetate, tocotrienol), vitamin A and derivatives (vitamin A palmitate), and coniferyl benzoate of benzoin resin, rutinic acid and derivatives thereof, xcex1-glucosylrutin, ferulic acid, furfurylideneglucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiac acid, nordihydroguaiaretic acid, trihydroxybutyrophenone, uric acid and derivatives thereof, mannose and derivatives thereof, zinc and derivatives thereof (e.g. ZnO, ZnSO4), selenium and derivatives thereof (e.g. selenomethionine), stilbenes and derivatives thereof (e.g. stilbene oxide, trans-stilbene oxide).
The amount of abovementioned antioxidants (one or more compounds) in the preparations is preferably from 0.001 to 30% by weight, particularly preferably from 0.05 to 20% by weight, in particular from 1 to 10% by weight, based on the total weight of the preparation.
If vitamin E and/or derivatives thereof are the antioxidant(s), it is advantageous to choose their respective concentration from the range from 0.001 to 10% by weight, based on the total weight of the formulation.
If vitamin A and/or derivatives thereof or carotenoides are the antioxidant(s), it is advantageous to choose their respective concentration from the range from 0.001 to 10% by weight, based on the total weight of the formulation.
Customary oil components in cosmetics are, for example, paraffin oil, glyceryl stearate, isopropyl myristate, diisopropyl adipate, cetylstearyl 2-ethylhexanoate, hydrogenated polyisobutene, vaseline, caprylic/capric triglycerides, microcrystalline wax, lanoline and stearic acid.
The total content of auxiliaries and additives can be from 1 to 80% by weight, preferably from 6 to 40% by weight, and the nonaqueous content (xe2x80x9cactive substancexe2x80x9d) can be from 20 to 80% by weight, preferably from 30 to 70% by weight, based on the compositions. The compositions can be prepared in a manner known per se, i.e. for example by hot, cold, hot-hot/cold or PIT emulsification. This is a purely mechanical process; no chemical reaction takes place.
Sunscreen preparations of this type can, accordingly, be in liquid, paste or solid form, for example as water-in-oil creams, oil-in-water creams and lotions, aerosol foam creams, gels, oils, wax pencils, powders, sprays or alcoholic-aqueous lotions.
Finally, it is also possible to co-use other substances which absorb in the UV region and are known per se, as long as they are stable in the overall system of the combination of UV filters to be used according to the invention.
Most of the light protection agents in the cosmetic and pharmaceutical preparations used for protecting the human epidermis consist of compounds which absorb UV light in the UV-B region, i.e. in the range from 280 to 320 nm. For example, the proportion of the UV-A absorbers to be used according to the invention is from 10 to 90% by weight, preferably from 20 to 50% by weight, based on the total amount of UV-B- and UV-A-absorbing substances.
The UV filter substances used in combination with the compounds of the formula I to be used according to the invention are any UV-A and UV-B filter substances. Examples which may be mentioned are:
The cosmetic and dermatological preparations according to the invention can further advantageously comprise inorganic pigments based on metal oxides and/or other metal compounds which are insoluble or sparingly soluble in water, in particular the oxides of titanium (TiO2), zinc (ZnO), iron (e.g. Fe2O3), zirconium (ZrO2), silicon (SiO2), manganese (e.g. MnO), aluminum (Al2O3), cerium (e.g. Ce2O3), mixed oxides of the corresponding metals, and mixtures of such oxides. Particular preference is given to pigments based on TiO2 and ZnO.
For the purposes of the present invention, it is particularly advantageous, although not obligatory, for the inorganic pigments to be present in hydrophobic form, i.e. to have been surface-treated to repel water. This surface treatment can involve providing the pigments, in a manner known per se, as described in DE-A-33 14 742, with a thin hydrophobic layer.
To protect human hair from UV rays, the light protection agents of the formula I according to the invention can be incorporated into shampoos, lotions, gels, hairsprays, aerosol foam creams or emulsions in concentrations of from 0.1 to 10% by weight, preferably from 1 to 7% by weight. The particular formulations can be used, inter alia, for washing, coloring or for styling the hair.
The compounds to be used according to the invention usually have a particularly high absorbancy in the region of UV-A radiation with a sharp band structure. Furthermore, they are readily soluble in cosmetic oils and can be readily incorporated into cosmetic formulations. The emulsions prepared using the compounds to be used according to the invention are notable in particular for their high stability and the preparations produced using it have a pleasant feel on the skin.
The UV filter action of the compounds to be used according to the invention can also be utilized for stabilizing active ingredients and auxiliaries in cosmetic and pharmaceutical formulations.
The compounds according to the invention are highly suitable for stabilizing organic materials against the effect of light, oxygen and heat.
Examples of plastics which can be stabilized by the compounds I according to the invention which may be mentioned are:
polymers of mono- and diolefins, such as, for example, low or high density polyethylene, polypropylene, linear polybut-1-ene,. polyisoprene, polybutadiene and copolymers of mono- or diolefins or mixtures of said polymers;
copolymers of mono- or diolefins with other vinyl monomers, such as, for example, ethylene-alkyl acrylate copolymers, ethylene-alkylmethacrylate copolymers, ethylene-vinylacetate copolymers or ethylene-acrylic acid copolymers;
polystyrene and copolymers of styrene or xcex1-methylstyrene with dienes and/or acrylic derivatives, such as, for example, styrene-butadiene, styrene-acrylonitrile (SAN), styrene-ethyl methacrylate, styrene-butadiene-ethyl acrylate, styrene-acrylonitrile-methacrylate, acrylonitrile-butadiene-styrene (ABS) or methylmethacrylate-butadiene-styrene (MBS);
halogen-containing polymers, such as, for example, polyvinyl chloride, polyvinyl fluoride, polyvinylidene fluoride and copolymers thereof;
polymers derived from xcex1,xcex2-unsaturated acids and derivatives thereof, such as polyacrylates, polymethacrylates, polyacrylamides and polyacrylonitriles;
polymers derived from unsaturated alcohols and amines and from their acrylic derivatives or acetals, e.g. polyvinyl alcohol and polyvinyl acetate;
polyurethanes, polyamides, polyureas, polyphenylene ethers, polyesters, polycarbonates, polyoxymethylenes, polysulfones, polyether sulfones and polyether ketones.
The compounds I according to the invention can also be used to stabilize surface coatings, e.g. industrial coatings. Of these, particular emphasis is given to stoving finishes, and of these, in turn, automotive finishes, preferably two-coat finishes.
The compounds I according to the invention can be added to the coating in solid or dissolved form. In this context, their ready solubility in coating systems is of particular advantage.
Preference is given to using the compounds I according to the invention for stabilizing polyolefins, in particular polyethylene, polycarbonates, polyamides, polyesters, polystyrene, ABS and polyurethanes. In particular, it is also possible to stabilize films made of said plastics.
For these fields of use, the compounds are used in concentrations of from 0.01 to 5% by weight, based on the amount of plastic, preferably in a concentration of from 0.02 to 2% by weight. The combination with other stabilizers, for example antioxidants, metal deactivators or other light protection agents, and with antistatic or flame-inhibiting agents, is often advantageous. Particularly important costabilizers are, for example, sterically hindered phenols and phosphites, phosphonites, amines and sulfur compounds.
Examples of suitable costabilizers are:
phenolic antioxidants such as
2,6-di-tert-butyl-4-methylphenol,
n-octadecyl xcex2-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate,
1,1,3-tris(2-methyl-4-hydroxy-5-tert-butylphenyl)butane,
1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene,
1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl)isocyanurate,
1,3,5-tris[xcex2-(3,5-di-tert-butyl-4-hydroxyphenyl)propionylethyl]isocyanurate,
1,3,5-tris(2,6-dimethyl-3-hydroxy-4-tert-butylbenzyl)isocyanurate and
pentaerythritol tetrakis[xcex2-(3,5-di-tert-butyl-4-hydroxy)propionate],
phosphorus-containing antioxidants such as
tris(nonylphenyl)phosphite, distearylpentaerythritol phosphite,
tris(2,4-di-tert-butylphenyl)phosphite,
tris(2-tert-butyl-4-methylphenyl)phosphite,
bis(2,4-di-tert-butylphenyl)pentaerythritol diphosphite and
tetrakis(2,4-di-tert-butylphenyl)-4,4xe2x80x2-biphenylenediphosphite,
sulfur-containing antioxidants such as
dilauryl thiodipropionate,
dimyristyl thiodipropionate,
distearyl thiodipropionate,
pentaerythritol tetrakis(xcex2-laurylthiopropionate) and
pentaerythritol tetrakis(xcex2-hexylthiopropionate),
sterically hindered amines such as
bis(2,2,6,6-tetramethylpiperidyl)sebacate,
bis(1,2,2,6,6-pentamethylpiperidyl)sebacate,
bis(l,2,2,6,6-pentamethylpiperidyl)ester,
N,Nxe2x80x2-bis(formyl)bis(2,2,6,6-tetramethyl-4-piperidyl)-1,6-hexane-diamine,
the condensation product of
1-hydroxy-2,2,6,6-tetramethyl-4-hydroxypiperidine and succinic acid,
the condensation product of
N,Nxe2x80x2-(2,2,6,6-tetramethylpiperidyl)hexamethylenediamine and
4-tert-octylamino-2,6-dichloro-1,3,5-s-triazine,
poly[3-(eicosyl/tetracosyl)-1-(2,2,6,6-tetramethylpiperidin-4-yl)pyrrolidin-2,5-dione],
tris(2,2,6,6-tetramethylpiperidyl)nitrilotriacetate,
tetrakis(2,2,6,6-tetramethyl-4-piperidyl)-1,2,3,4-butanetetra-carboxylic acid,
1,1xe2x80x2-(1,2-ethanediyl)bis(3,3,5,5-tetramethylpiperazinone), the condensation products of
4-amino-2,2,6,6-tetramethylpiperidines and tetramethylolacetylenediureas, and
2-(2xe2x80x2-hydroxyphenyl)benzotriazoles,
2-hydroxybenzophenones,
aryl esters of hydroxybenzoic acids,
xcex1-cyanocinnamic acid derivatives,
nickel compounds or
oxalic dianilides.
For mixing the compounds I according to the invention, especially with plastics, it is possible to use all known equipment and methods for incorporating stabilizing agents or other additives into polymers.

Use of cyclic enamines as light protection agents

Abstract: The use of compounds of the formula I

Abstract: in which

Abstract: where R3 is as defined above,

Abstract: where R4 can be bonded one or more times to the benzylidene ring I or naphthylidene ring II, and is hydrogen, alkyl, cycloalkyl, alkyloxy, cycloalkyloxy, alkoxycarbonyl, mono- or dialkylaminocarbonyl, alkylamino, dialkylamino, each having up to 20 carbon atoms, and also cyano, amino and SO3xe2x80x94M+, where M+ is a cation,


The present invention relates to a preparation which contains at least one physiologically effective iron complex and at least one polyunsaturated fatty acid in free or chemically bonded form, in particular for use as a medication and/or food supplement. The preparation according to the invention may be preferably used for manufacturing a medication and/or food supplement for treating or the prevention of deficiency symptoms as they may occur during pregnancy and breastfeeding. Furthermore antioxidizing agents and folic acid may be contained in the preparation according to the invention.

I claim priority under 35 U.S.C. xc2xa7 119 for European application Nr. 99810681.9-2114 which is hereby incorporated by reference in its entirety and for all purposes.
The invention relates to a preparation according to the preamble of claim 1, in particular for the use as a medication and/or as a food supplement.
The human body relies on the supply of a series of essential substances which it is not in the position to synthesise itself. There is a risk of an under-nourishment of these substances with an insufficient or one-sided food intake. In spite of a sufficient and balanced food intake, an undersupply of certain substances may occur under certain stress situations. Stress situations occur to the first degree with particular physical exertion, such as for example with serious sports, or also during pregnancy and breastfeeding.
Also during pregnancy and breastfeeding there are a series of substances which are necessary for the healthy development of the child and for the health of the mother. One of the most important substances from the class of vitamins has been shown to be folic acid. As medical studies show there is a clear connection between folic acid deficiency symptoms and the feared neural tube defect with newborn children, such as e.g. published by R. D. Williams, FDA Consumer, May 1994, page 11-12 and O. Txc3x6nz, Schweizer Apothekerzeitung, 1996, 17, pages 424-426.
More recent trials indicate the conclusion that a sufficient supply of polyunsaturated fatty acids in free form and/or as glycerides is likewise not to be neglected during pregnancy and breastfeeding
Polyunsaturated fatty acids can belong to three different families which differ by way of the position of the first double bonding, calculated from the methyl end of the fatty acids. In medical studies
xcfx89-3-polyunsaturated fatty acids (linolenic acid family);
xcfx89-6-polyunsaturated fatty acids (linoleic acid family) and
xcfx89-9-fatty acids have shown to be physiologically important.
The polyunsaturated fatty acids of the xcfx89-3 and xcfx89-6 type are precursors for forming important tissue hormones such as e.g. prosetaglandine or leukotriene. Several independent studies render the conclusion that a higher intake of polyunsaturated fatty acids from the xcfx89-6 and xcfx89-3 series improves the sharpness of vision of newborn children and generally encourages the infant brain development. With this, 5,8,11,14-eicosatetranoic acid and docosahexaenoic acid as metabolites of linoleic and linolenic acids appear to play a particular role (D. Kunze, 49. DGF Annual Meeting on 01.09.1993 in Karlsruhe).
The female body by way of pregnancy is subjected to an increased oxidative stress. Oxidative stress is indicated as an increased activity of free radicals. This may either be caused by way of a higher production of free radicals or by way of the undersupply of protective anti-oxidatively acting substances. Amongst other things the increased oxidative stress in vivo is held to be responsible for the pregnancy-induced high blood pressure, as cited in S. J. Wisdom, R. Wilson, J. H. McKillop, J. J. Walker, Am. J. Obstet, Gynecol., 12/1991, page 1701-1704. In particular in pregnancy there exists the requirement for anti-oxidatively acting substances.
The term antioxidant agents is to be understood as organic compounds which inhibit or prevent the undesired changes in other substances caused by the effect of oxygen and other oxidative processes. Tocopherols, carotinoids, tocotrienols, ascorbic acids, selenium, polyphenols, flavonoides, flavones are known as radical scavengers or participate closely with the respiratory chain and thus protect the functional and structural intactness of lipids and other important substances such as blood, biomembranes and cell contents.
Iron has a particular importance with regard to minerals and trace elements. The iron requirement of mother and child is an important factor of prenatal and postnatal health on account of the build-up of special foetal haemoglobin, whose conversion after birth serves in filling the iron store in kidney and liver.
Bivalent iron saltsxe2x80x94in the oral administering formxe2x80x94are to be seen as the most effective iron intake substances. The degree of iron uptake is however relatively small. In order to ensure a sufficient bio-availablity the administering of high quantities of iron salts is often necessary. High quantities of iron salts and in particular the free iron ions arising by way of dissociation leads to incompatibility reactions such as sickness, vomiting and diarrhea or constipation. Trivalent iron salts as iron suppliers are practically ineffective since in the intestines they break down into iron oxide or iron hydroxides.
A further problem which is linked to the administering of Fe(II) are lipid-peroxidation processes of unsaturated fatty acids which apart from other causes also run their course under the catalytic effect of iron (II). By way of the lipid peroxidation there arise mutagenic and carcinogenic substances such as e.g. xcex1 and xcex2 unsaturated aldehydes. However also damage to cell membranes and other cell components may be led back to these oxidisation processes.
Anti-oxidant agents act as radical scavengers with lipid peroxidation procedures and in this manner may end chain reactions. On the other hand the substances used as radical scavengers change themselves with the xe2x80x9cneutralisationxe2x80x9d. In any event this is not desirable in the case that vitamins as essential substances are to be supplied to the body.
The auto-oxidation of unsaturated fatty acids in the presence of oxygen and catalysts plays a decisive and in its effects not desired role when fats or oils become rancid (S. Ullmann""s Encylopedia of Industrial Chemistry, Eds. L. Kandy, J. F. Rounsville, G. Schulz, 5th ed., Vol A 10, pages 190 onwards., 1987). This process is encouraged or accelerated by the presence of metal catalysts.
In particular, free fatty acids and volatile carbonyl compounds such as e.g. aldehydes and keto-compounds arising by way of the auto-oxidation are responsible for the unpleasant accompanying taste and odour of aged fat.
The primary products formed by auto-oxidation, such as hydroperoxides, the acid number and the number of volatile carbonyl compounds, in particular the aldehydes, serve as a measurement parameter and for fixing limit values for the storage and manufacture.
The formulation of a preparation which contains a combination of polyunsaturated fatty acids in free or chemically bonded form and physiologically effective iron salts, in particular iron (II) salts, is for reasons of the reactivity of the substances and the instability of such preparations resulting therefrom burdened with great difficulties and has until now not been realised.
The object of the present invention is the avoidance of disadvantages of the state of the art.
In particular it is the object to combine physiologically effective iron-containing compounds with unsaturated fatty acids in a free or chemically bonded form into a preparation without there occuring a considerable reduction of the physiological effectiveness of one or both components. The combination should be possible without preceding complicated protective steps such as e.g. a micro-encapsulation of individual or of all components.
A further object lies in the preparation of a storage-stable, multi-component preparation which apart from physiologically effective iron-containing compounds and unsaturated fatty acids in free and/or chemically bonded form further contains physiologically effective components, and in particular is used for manufacturing a medication and/or a food supplement for the prevention and treatment of deficiencies.
These objects are achieved by the characterising features of patent claim 1.
In particular they are achieved by a preparation which contains at least one physiologically effective iron complex and at least one unsaturated fatty acid in free and/or chemically bonded form.
xe2x80x9cPhysiologically effectivexe2x80x9d is to be understood in that the iron complex on the one hand does not create any or only insignificant undesired side effects in the human body and on the other hand is in the position of preventing or treating and relieving iron deficiency.
The preparation according to the invention may preferably be used as a medication and/or as a food supplement.
In the broadest sense the term xe2x80x9ccomplexxe2x80x9d is to be understood as a compound of a higher order which formally arises by the stochiometric combination of molecules and/or ions capable of existing individually or independently of one another. This is to be understood in contrast to the compounds of first order in for creation of which atoms are involved. In the course of formation of complexes several uncharged or charged (one or more) groups L (ligands) are added to an uncharged or charged atom Z (the central atom or ion) according to its coordination number n. Iron as a transition metal bonds such ligands which have free or xcfx80-electron pairs at their disposal and which may interact with the vacant hybrid orbitals of the iron for forming a complex.
In a preferred embodiment the ligands are at least bidentate, i.e. ligand or ligands with at least two complex-forming atoms may add a central atom and form the so-called chelate compounds. As a rule the complex-forming atoms are O, S and N. Complexes with bidentate and multidentate chelate ligands are more stable than complexes with non-bridged ligands.
Since the physiologically effective iron complexes are acting in the body in competition with other complex formers, such as they are made available by the diet (proteins, peptides, polycarbon acids, sugars, phosphates, thiols and other potential ligands in the intestinal tract), the complex stability must be so large that the iron complex applied is not essentially subjected to competition reactions with xe2x80x9ccompetitivexe2x80x9d complex formers. The stability must however be smaller than that of the mucosal transferin so that the iron may be taken over at the acceptor locations of the transfer system. The complex stability must preferably be so large that the occurence of free iron ions in water and preferably also under pH conditions as they are in the stomach or intestinal tract essentially does not take place. The iron complexes used in the preparation according to the invention may however have a certain water solubility.
Iron complexes which fullfill the above mentioned conditions and are applied for treating iron deficiency are known. It has now been surprisingly ascertained that at least one of these iron complexes and at least one poly-unsaturated fatty acid in free or chemically bonded form can be combined in a preparation without there occuring any significant changes under standard conditions within 6 months, e.g. by oxidation and hydolysis processes of the unsaturated fatty acids.
The preparation according to the invention should not exceed peroxide numbers (UOP) of 10 (meq 02/kg), preferably the UOP lies at a highest value of 5 meq 02/kg and even more preferred with maximum values of 3 meq 02/kg (method 7/5.2 according to the xe2x80x9cSchweizer Lebensmittelbuch, July 1994). Furthermore the evaluation of the aldehydes and free fatty acids serves as a measuring parameter.
As standard conditions there are defined a temperature of 25xc2x0 C. xc2x12xc2x0 C., a relative air humidity of 60% +5% and a pressure of 1 bar.
In a preferred embodiment of the present invention the iron has a oxidation step of +III in the iron complex. A further preferred embodiment form is the iron in the oxidation step xc2x10 in the iron complex.
The use of complexes which contain iron in the oxidation step +II and which correspond to the mentioned conditions may likewise be applied in the preparation according to the invention either solely or in combination.
For the preparation of the present invention physiologically effective iron(III) complexes are suitable with the precondition that they fullfill the already mentioned conditions.
Preferably the 3-hydroxy-4-pyrone iron complexes and derivatives thereof described in EP 107 458 are applied. The derivatives comprise those 3-hydroxy-4-pyrone iron complexes in which one or more of the hydrogen atoms of the pyrone ring is replaced by an aliphatic carbon chain. Preferably the carbon chain contains one to six carbon atoms. In a preferred embodiment the derivative of 3-hydroxy-4-pyrone is maltol (3-hydroxy-2-methyl-4-pyrone).
The 3-hydroxypyrid-2-on iron complexes and derivatives of this described in EP 0 094 149 are further used in the preparation according to the invention.
Iron(III)-hydroxide-polymaltose complexes, as are described in the xe2x80x9cDeutsche Apotheker Zeitungxe2x80x9d, 121 Year, No. 41, page 2193 to 2195 by H. Jakobs have also been shown to be suitable according to the invention.
As iron complexes which have iron in the oxidation step 0, iron pentacarbonyl complexes (iron-ferronyl according to Food Chemical Codex, 4th ed., 1999) and ferrocene have been shown to be particular suitable.
The preferred Fe(III) 3-hydroxy-4-pyrone-complexes, as well as Fe(III) 3-hydroxy-4-pyrid-2-one complexes and their derivatives, in particular maltol may be present in the neutral form and thus at a ratio of ligand : Fe(+III) of 3:1. But also iron(III) complexes which have molar ratios of the ligands : iron of 2:1 and 1:1 may be applied according to the invention and in the course of the present invention fall under the description of the neutral form. These ratios however render necessary the presence of further anions such as chloride in order to compensate the charging of the central atom.
The Fe(III) content may according to the complex also vary within the same type of complex. As a daily iron intake of an adult generally a quantity between 2 to 4 mg or iron is seen as sufficient. The quantity of the iron complex used in the preparation according to the invention should accordingly be present such that iron is present in the preparation between 0.1 to 20 mg, preferably in a region of 5 to 18 mg and even more preferred in a region of 10 to 15 mg, in order to alleviate iron deficiency. These values relate to a single daily intake of a suitable administering form.
Apart from the iron(III)-hydroxypyron, iron(III)-hydroxypyridon and iron(III)-hydroxide-polymaltose complexes which may be applied either alone or in combination with one another, further
Fe(III) complexes such as iron(III)-citrate complexes may likewise be applied alone or in mixtures with the previously mentioned complexes in the preparation according to the invention.
A further factor which plays a role with the bio-availability of iron is the ability of the iron complexes to penetrate biological membranes. One of the possible indicators for this membrane permeation is Kpart. Kpart describes the ratio between the concentration of the compound in n-octanol to the concentration of the compound in the aqueous phase. Although the iron complex as well as its corresponding metal-free compound should be able to enter through the biomembrane, both should also have a certain degree of water solubility. In the course of the present invention the iron complexes preferably have Kpart values in a region between 0.02 and 6.0, preferred between 0.1 and 4.0 and even more preferred between 0.2 and 1.0. The metal-free complex preferably has Kpart values between 0.05 and 3.0, preferred between 0.1 and 2.0 and even more preferred between 0.2 and 1.0.
In a preferred embodiment form the unsaturated fatty acids used in the preparation according to the invention in free or chemically bonded form are selected from the group consisting of xcfx89-3 and xcfx89-6 polyunsaturated fatty acids.
The term xe2x80x9cchemically bondedxe2x80x9dshould stand for all the unsaturated fatty acids which are present other than as a free form, e.g. in the form of their glycerides (monoglyceride, diglyceride or triglyceride) in oils, fats or other types of esters. They are used alone or in mixtures with one another.
Preferably they are, in the form in which they occur with their extraction, combined with the remaining components in the preparation according to the invention, so that e.g. docosahexaenoic acid and eicosatetraenoic acid are present in concentration and structure as e.g. in fish oils. They may however also be purified, highly enriched and when required re-estered as glycerides or fatty acids.
Preferably the xcfx89-3 polyunsaturated fatty acids belong to the linolenic acid family, whilst the xcfx89-6 polyunsaturated fatty acid preferably come from the linoleic acid family.
The xcfx89-3 and the xcfx89-6 polyunsaturated fatty acids are preferably applied in a quantity of 5 to 75% by weight with respect to the total weight of the preparation, preferably in a quantity of 30 to 70% by weight and even more preferred in a quantity of 50 to 60% by weight. These quantities may be obtained from one of the fatty acids alone or from mixtures of both.
For most of the substances which may be applied in the preparation according to the invention a quantity specification is preferred which is directed towards the RDA (recommended daily allowance) values. The quantity of acids from the linolenic and linoleic acid family, in particular of xcfx89-3 and xcfx89-6 fatty acids lies between 30 mg and 100 mg (100% free fatty acid) per administering form with a single daily intake, preferred between 50 mg and 800 mg and even more preferred between 80 and 250 mg.
In a preferred embodiment form the xcfx89-3 unsaturated fatty acid is docosahexaenoic acid (C-22: (xcfx89-3) and/or eicosapentaenoic acid and/or eicosatetraenoic acid. Docosahexaenoic acid and eicosapentaenoic acid occur as a mixture in particular in fish oils.
In a further preferred embodiment form the unsaturated fatty acids of the linolenic and linoleic acid family are of a vegetable origin and are contained in fatty oils as e.g. are extracted from borage or evening primrose.
Particularly advantageous in the preparation according to the invention fat-soluble and water-soluble radical scavengers from the group of tocopherols, carotinoids, tocotrienols, polyphenols, flavonoides, flavones and ascorbate as well as additional water and/or fat soluble vitamins are applied.
As antioxidants from the group of water-soluble substances preferably ascorbic acids, flavonoides and flavones are applied in the preparation according to the invention. For reasons of stability ascorbic acid however may not be applied in a combination with iron ferronyl.
As antioxidants from the group of fat-soluble substances preferably the carotenoides (carotene, lutein, lycopin, zeaxanthin, etc.) and tocotrienols are applied. Fat-soluble vitamins with a radical scavenger function in particular are tocopherols from the vitamin E group to which also there are counted the esters of xcex1, xcex2, xcex3, xcex4-tocopherols.
With a single daily administering of the preparation according to the invention the administering form for adults should contain a quantity of carotenoids ( greater than 60% xcex2-form) and polyhydroxy phenols such as flavonoids, flavones, etc.) between 4 and 25 mg, preferably from 6 to 15 mg. The quantities of vitamins is directed towards the RDA values (adults between 25 and 50 years) and for a single daily intake per administering form for adults the ranges for vitamin C lies between 20 mg and 100 mg, for vitamin E between 10 and 25 mg.
In a further preferred embodiment form the preparation according to the invention additionally contains folic acid in a quantity per administering form with a single daily intake in a range of 0.1 g to 0.6 g (87.8% purity) preferably in a quantity of 0.2 g to 0.5 g and even more preferred from 0.25 to 0.4 g.
Folic acid simplifies the treatment of anaemia which leads back to iron deficiency and furthermore, as already described, is used for the prevention of neuron tube defects.
Furthermore to the preparation according to the invention there may also be applied a zinc source in a quantity per administering form (single daily intake) of 0.5 to 20 mg, preferably from 5 to 17 mg and even more preferred from 12 to 15 mg.
In particular the preparation according to the invention may be used for manufacturing a medication and/or food supplement for treating and preventing deficiency symtoms.
Particularly a combination of folic acid, anti-oxidant agents, in particular anti-oxidatively acting vitamins, physiologically effective iron complexes and unsaturated fatty acids in a free and/or chemically bonded form, in particular with fatty acids of the xcfx89-3 and or xcfx89-6 type have been shown to be advantageous in pregnancy and breastfeeding. In particular by way of the iron complex although the iron intake is ensured, undesired side and catalytic effects of the iron are however prevented. This firstly is to be led back to the low concentration of free iron ions since the iron quantities released from the complex are directly taken up by the body. The concentration of free iron ions thus in the preparation as well as in the body lie below that quantity which to a significant degree causes undesired changes of bodily or other compounds.
The preparation according to the invention can be comprised in administering form which contains the preparation in quantities which are sufficient for a single daily intake. The required daily quantities of the physiologically effective substances in the preparation according to the invention may however also be distributed into two or more administering forms over the day. Suitable as an administering form are capsules (hard capsules (secured by stamp and sealed) and soft capsules), drink solutions and syrup. The encapsulation in e.g. soft gelatine, hard gelatine and starch capsules has been shown to be particularly suitable.
The encapsulation is effected in a closed system in nitrogen under largely water-free conditions after a heavy drying of the individual content substances.
Depending on the administering form various auxiliary substances and substrates are applied. There are applied e.g. bees wax as water protection and for increasing the viscosity, monoglycerides and diglycerides of edible fatty acids as emulsifiers, sorbitol/manitol as non-diffusing softeners (if in the administering form of a capsule), aromas for rendering inert the smell and taste of e.g. fish oil.
Soft gelatine and starch capsules which encapsulate the preparation according to the invention are preferably manufactured with the rotary die procedure.
The administering forms, in particular in the embodiment form as a capsule may have coatings resistant to gastric juice in order (where appropriate according to the composition of the preparation) to achieve a delayed release (in the intestine). Also the cross-linking of the gelatine or derivates of starch in the casing may create certain retard effects according to the composition of the preparation.
The invention is further explained by way of examples.
Determining the Kpart value:
Determined is the distribution in each case for the iron complex as well as for the corresponding metal-free compound between n-octanol and aqueous tris hydrochloride (20 mM, pH 7.4; tris: 2 amino-2-hydroxymethylpropane-1,3-diol). The concentration of the substances in the respective phase is measured at 20xc2x0 C. by way of spectrophotometry. 5 ml of a 10xe2x88x924M aqueous solution of iron complex and metal-free compound are mixed with 5 ml of n-octanol for one minute. The aqueous n-octanol mixture arising with this is centrifuged at 1,000 G for 30 seconds. The two resulting phases are separated from one another for evaluating the concentration. The metal-free compound is measured in a region of 220 to 340 nanometers whilst for evaluating the concentration of the corresponding iron complex a region between 340 and 640 nanometers is selected. These regions also apply to the 3:1 maltol-iron(III)-complex.
The subsequent tables shows Kpart values of a few selected complexes.

Preparation in particular for use as a medication and/or food supplement


An adhesive tape comprising: (a) a polymer film; (b) a primer coat on said polymer film; and (c) an adhesive layer on the primer coat comprising: (i) a natural rubber latex; and (ii) a tackifier.

This is a non-provisional application of prior pending U.S. provisional application Titled xe2x80x9cPRESSURE SENSITIVE ADHESIVE TAPE CONTAINING NATURAL RUBBER LATEXxe2x80x9d, filed Jan. 15, 2001.
This invention relates generally to an adhesive tape comprising a tackified natural rubber latex and a primer.
The use of natural rubber in pressure sensitive adhesives is well known. Such adhesives employ solvent-borne natural rubber, in which rubber obtained by centrifuging natural rubber latex is masticated and applied to a backing material from a solvent solution. The mastication process decreases the molecular weight of the rubber, which is believed to result in improved adhesion, possibly at the expense of cohesive strength.
There has been no significant commercial production of adhesive coatings made from water-borne rubber to date, despite the fact that environmental and health factors would favor the use of water-borne rubber. Anchorage of the adhesive to the filmic backing is a critical problem in natural rubber latex adhesive tapes. When rolls of the tape are unwound, delamination and adhesive transfer to the back side of the film remaining on the roll frequently occur. A related concern is that the tapes generate considerable noise on commercial lines when they are unwound for slitting into small rolls of adhesive tape.
Adhesive tapes from waterborne natural rubber latex have been known since the 1940""s, when methods were developed to incorporate water-insoluble solid tackifiers into aqueous dispersions. The problem of anchorage was addressed by incorporating addition polymer emulsions. Unfortunately, addition polymers are detrimental to the adhesive properties of the tape and thus are not commercially useful.
Japanese patent application, JP 11-172212 (1999), suggests that an adhesive comprising natural rubber latex, synthetic rubber latex, and an ethylene-vinyl acetate-acrylate copolymer emulsion provides good anchorage. All examples without the EVA copolymer have poor anchorage and high unwind noise due to stepped delamination. However, this reference acknowledges that use of the EVA copolymer has a detrimental effect on the adhesive properties, a deficiency which is partially overcome by the use of the synthetic rubber.
The problem addressed by this invention is to find a pressure sensitive tape adhesive containing natural rubber latex and having a good balance of adhesive properties, as well as anchorage. An additional benefit for a pressure sensitive tape would be low noise upon unwinding.
The present invention is directed to an adhesive tape comprising: (a) a polymer film; (b) a primer coat on said polymer film; and (c) an adhesive layer on the primer coat, the adhesive layer comprising: (i) a natural rubber latex; and (ii) a tackifier.
The term xe2x80x9cadhesive tapexe2x80x9d includes, for example, packaging tape, printable tape, specialty tape and protective film.
The term xe2x80x9cpolymer filmxe2x80x9d refers to any polymer in the form of a film suitable for manufacture of an adhesive tape. The preferred polymer films are those made from polyolefins, including but not limited to polypropylene, polyethylene and copolymers and combinations thereof; polyester; and polyvinyl chloride (PVC). The most preferred polymer film is oriented polypropylene film (OPP). Preferably, the polymer film has undergone corona or flame treatment to improve anchorage prior to being coated with primer and adhesive.
The term xe2x80x9cacrylic polymersxe2x80x9d refers to polymers of acrylic acid, methacrylic acid and their esters, and copolymers predominantly comprising the aforementioned monomers.
The term xe2x80x9ctackifierxe2x80x9d refers to a resin or combination of resins which imparts tack to an adhesive formulation, especially in the context of a tape adhesive. Preferred tackifiers include rosin tackifiers, polyterpene resins, aliphatic hydrocarbon resins, aromatic petroleum resins, phenol resins, styrene resins and coumarone-indene resins. A xe2x80x9crosin tackifierxe2x80x9d is a tackifier derived from a rosin, including but not limited to rosins, rosin esters, rosin derivatives, hydrogenated rosins, hydrogenated rosin esters and hydrogenated rosin derivatives. The rosin tackifier is included as the solid resin or as a liquid dispersion or emulsion. The preferred rosin tackifier is a rosin ester tackifier.
The term xe2x80x9cprimerxe2x80x9d refers to a solvent-based or aqueous material applied to a polymer film backing to form a primer coat, thereby increasing anchorage of a tape adhesive to the film. Preferably, the primer is a solvent-based or aqueous polymer composition in which the polymeric component has a Tg no greater than xe2x88x9210xc2x0 C. Most preferably, the primer is an aqueous polymer composition in which the polymeric component has a Tg no greater than xe2x88x9210xc2x0 C., and which contains a crosslinking agent. Preferred primers include solvent-based or aqueous acrylic polymers, ethylene-vinyl acetate copolymers, ethylene-vinyl acetate-acrylic copolymers, styrene-butadiene copolymers, and styrene-butadiene-acrylonitrile copolymers. In a preferred embodiment of the invention, the polymeric component of the primer comprises from 0.2% to 20% of monomer units bearing a functional group suitable for crosslinking, e.g., carboxylic acid, hydroxyl, and amine; more preferably from 1% to 5%. Still more preferably, the polymeric component is an acrylic polymer having a Tg no greater than xe2x88x9210xc2x0 C. and comprising from 1% to 5% of acrylic acid or methacrylic acid monomer units, most preferably from 1.5% to 2.5%.
Preferably, at least one crosslinking agent is added to the primer, preferably before coating the primer on the polymer film. A crosslinking agent is a material effective for crosslinking, e.g., via hydroxyl or carboxylic acid functional groups in an aqueous medium or in a solvent. Preferably, one of the crosslinking agents well known in the art is used with a primer whose polymeric component bears the appropriate functional groups. These crosslinking agents include, but are not limited to, difunctional or polyfunctional isocyanates, blocked isocyanates, carbodiimides, diamines, triamines, polyamines, aziridines, amine functional resins, e.g., melamines and urea-formaldehyde resins, epoxy resins, epoxides, acids, anhydrides and polymers with conjugated unsaturation. Preferred crosslinking agents are those which are effective for crosslinking via both hydroxyl and carboxylic acid functional groups, especially difunctional or polyfunctional isocyanates and carbodiimides. Preferably, the crosslinking agent is added to the primer at a level from 1% to 20% by total weight of primer, most preferably from 2% to 10% by total weight of primer.
The primer typically is coated onto the film to form a primer coat with a dry coat weight from 0.5 to 6 g/m2, preferably from 2 to 3 g/m2. The adhesive layer is applied to the primer coat. Preferably the primer coat is dried prior to application of the adhesive. layer. In a preferred embodiment of the invention, the primer coat has been crosslinked by a crosslinking agent present in the primer.
Preferably, the adhesive layer contains less than 25% of a synthetic rubber. Most preferably, the adhesive layer is substantially free of synthetic rubber, e.g., polyisoprene or styrene-butadiene rubber, or other synthetic polymers.
In one embodiment of the invention, the adhesive contains from 1% to 10% of latex particles each of which has a void and a particle size from 50 to 500 nm, as described in U.S. Pat. No. 5,663,213. Such particles act as uv absorbers in the adhesive. Preferably, the adhesive contains from 3% to 6% of said latex particles.
The adhesive tape optionally contains other additives typically used in adhesive tapes, e.g., antioxidants, uv stabilizers, mechanical stabilizers, surfactants, defoamers, pigments, humectants and plasticizers.
The present invention is directed also to an adhesive tape produced by: (a) applying a primer to a polymer film to form a primer coat; and (b) applying to the primer coat an adhesive comprising: (i) a natural rubber latex; and (ii) a tackifier. Preferably, the natural rubber latex and the tackifier are mixed to form an adhesive, which is then applied to the primer coat. Preferably, the primer coat is dried prior to application of the adhesive.

Pressure sensitive adhesive tape containing natural rubber latex


An infant crib wherein the crib portion is elevated in order to accommodate a wheelchair passing under the crib bed. The invention is preferably comprised of spaced support members supporting a horizontal base member at an elevated position high enough to accommodate the seat portion of a wheelchair beneath the base member. There is at least one side panel surrounding the base member slidable laterally between a closed and open position to enable a person seated in a wheelchair to have access to an infant placed on the base member when the slide panel is in the open position. A drawer member is positioned under the base member to allow a person seated in a wheelchair to have access to any necessary items.

This invention relates to an infant crib and more particularly relates to a novel and improved infant crib elevated to accommodate a wheelchair beneath the crib bed.
Over the years a number of infant cribs have been developed to accommodate various special needs. There is specifically lacking, in the area of infant cribs, an elevated crib designed to allow the seat portion of a wheelchair to pass under the crib bed. Typical cribs have a rail or panel that is capable of sliding vertically. The raising and lowering of the side panel prevents any object, such as a wheelchair, from passing underneath the crib bed. Further, typical infant cribs are not elevated to the extent of allowing a wheelchair to pass underneath the crib bed.
It has been found that by elevating the crib bed, mounting the side panel to slide laterally and adding a drawer to hold infant necessities within hand""s reach, the problems encountered by individuals who are wheelchair-bound, seeking to attend to an infant inside of the crib are addressed. Further, this infant crib may also be used by individuals requiring an elevated crib due to aging, a bad back or similar condition, alleviating the need to excessively bend over while tending to an infant inside the crib.
It is therefore an object of the present invention to provide for a novel and improved infant crib wherein the crib is elevated to accommodate a wheelchair passing underneath the crib bed.
It is another object of the present invention to provide for a novel and improved infant crib in which at least one side panel is laterally slidable between a closed and open position to enable a person in a sitting position or confined to a wheelchair to have access to an infant in the crib.
It is another object of the present invention to provide for a novel and improved infant crib having a drawer secured under the crib bed at arm""s reach of the person seated in a wheelchair, in order to obtain any necessary infant products, such as, diapers, lotions or creams.
It is another object of the present invention to provide for a novel and improved infant crib in which a lateral sliding side panel has a stop mechanism preventing the panel from sliding completely off the slide rail.
It is a further object of the present invention to provide for a novel and improved infant crib in which the lateral sliding side panel is prevented from disengaging from the slide rail through use of a modified side rail and can be easily moved by one seated in a wheelchair.
Another advantage of the present invention is that the lateral sliding side panel can be secured to a crib frame in such a way as to prevent an infant from inadvertently falling out of the crib.
A further advantage of the present invention is that an individual confined in a wheelchair may tend to an infant located inside of the crib while at the same time retrieving any necessary articles without leaving the infant unattended.
In accordance with the present invention, there is provided an infant crib that broadly comprises a horizontal base member with spaced support members attached and supporting the base member at an elevated position high enough to accommodate the seat portion of a wheelchair beneath the base member, and including upright slide panel means slidable laterally between a closed and open position. A drawer or platform is attached to the base member allowing quick access to any infant necessities.
There has been outlined, rather broadly, the more important features of the invention in order that the detailed description thereof that follows may be better understood, and in order that the present contribution to the art may be better appreciated. There are, of course, additional features of the invention that will be described hereinafter and which will form the subject matter of the claims appended hereto. In this respect, before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description. The invention is capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting. As such, those skilled in the art will appreciate that the conception, upon which this disclosure is based, may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present invention. It is important, therefore, that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention.

Elevated infant crib designed for wheelchair access


A method of reducing the flyaway effect occurring during treatment of hair with a cosmetic composition is disclosed. According to this method an effective amount of an electrically conductive polymer is added to the cosmetic composition prior to treatment of the hair. Preferably the cosmetic composition is a shampoo or hair care composition, which contains from 0.001 to 5% of the electrically conductive polymer.

The subject matter of the invention is a cosmetic composition containing an electrical conductive polymer. The composition especially is a hair treatment composition in the form of a shampoo or a hair care composition and reduces the flyaway effect when hair is treated with it.
Freshly washed hair, especially thin hair, is inclined to stand out from the head after drying because of an acquired static charge. This so-called flyaway effect is troublesome. Conventional solutions for this problem involve use of styling agents, such as hair sprays, hair fixing agents or foams, which however have the disadvantage that they fix the hair and limit the natural mobility of the hairstyle. One other solution is the use of quaternarized care materials, e.g. cationic surfactants or cationic polymers, which load the hair and lead to a reduction of the electrostatic charge. Conventional hair-conditioning preparations, such as rinse-off care compositions or leave-on care compositions, are usually formulated as aqueous emulsions. The essential ingredients include cation-active substances, such as cationic surfactants, hydrophobic substances, such as fatty alcohols, and other oily components, emulsifiers, and additional specific active ingredients and perfumes. The most important ingredients are cationic surfactants, fatty alcohols and emulsifiers. A review of the principal ingredients of care rinses and hair care compositions is given by Schrader, xe2x80x9cFoundations and Compositions of Cosmetics (Grundlagen und Rezepturen der Kosmetika)xe2x80x9d, 2nd Edition, 1989, pp. 728 to 737. The principal purposes of the conditioning agents are the improvement of the stylability, the combability, the luster and feel of the treated hair. The application of the cationic care ingredients to the hair however leads to a comparatively heavy burden or loading of the hair as well as the desired effect, because of the comparatively large amount of required care ingredients. Loading of the hair however leads immediately to negative styling properties, especially in the case of fine hair. The treated hair feels heavy and loaded, which is not always desirable.
It is an object of the present invention to provide a cosmetic composition, which has typical hair care properties and especially which reduces the flyaway effect.
It is an additional object of the present invention to provide a cosmetic composition, which at least reduces an impression of the treated hair being heavy and loaded in comparison to hair treated with the conventional hair care compositions.
It is a further object of the present invention to provide a cosmetic composition, which avoids impairing the mobility of the hairstyle in comparison to that obtained by treatment with a conventional styling composition.
It has been surprisingly found that these objects can be attained by cosmetic compositions comprising an electrically conductive polymer.
According to the invention the cosmetic composition contains at least one electrically conductive polymer in a suitable cosmetic foundation.
In order to avoid the above-described flyaway effect without the troublesome side effects obtained by using conventional styling and care ingredients and to reduce the static charge, new intrinsically conductive polymers are used. By applying the hair treatment compositions according to the invention, which contain these polymers, the flyaway effect can be avoided. These polymers are known from other fields of art different from the cosmetic arts. They are used for treatment of surfaces, in order to avoid static charges, e.g. on electronic components or photographic films. They are applied by conventional application methods, such as spraying, pressing or brushing, among others. It has now been found that they may also be worked into a hair treatment composition without difficulty. In the treated hair the flyaway effect is clearly reduced. Only very small amounts of the conductive polymer are required and the hair feels light and not loaded in comparison to the result of treating with a conventional hair care product.
Intrinsically conductive polymers are usually ethylenically unsaturated and conjugated, whereby charge transport is possible in the polymer molecule. This type of polymer is also called an organic metal. They have a conductivity of at least 10xe2x88x925, preferably of at least 10xe2x88x922, especially preferably at least 1, siemens/cm. Suitable intrinsically electrically conductive polymers include, for example, polymeric compounds based on polyaniline, polyanisidine, polydiphenylamine, polyacetylene, polythiophene, polythioprene, polythienylvinylene, bithiophene, polypyrrole and polycroconaine and its derivatives. This sort of polymer is frequently made electrically conductive by doping. The doping can occur chemically or electrochemically. The polymeric compounds are partially oxidized by treatment with an oxidizing agent, such as iodine, sodium peroxydisulfate or bromine or other strong acids and are thus made electrically conductive. Other polymers could be made electrically conductive by partial reduction with a reducing agent. These methods are generally known in the art. The manufacture of intrinsically conductive polyaniline and polypyrrole is described, for example, in EP 0 539 123. Suitable polymer compounds are, e.g., polyradical cations. For increased stability of the formulation it is recommended that the polyradical cations be used in combination polymeric anionic compounds (polyanions) and that the composition does not contain any additional cationic substances, which compete for the counter ions and lead to failures.
The preferred conductive polymeric compounds are conductive polythiophenes, especially conductive polyalkylenedioxythiophene. These polymeric compounds are made by methods described in DE 41 18 704 and EP 0 339 340. 3,4-polyethylenedioxythiophene is especially preferred as the electrically conductive polymeric compound. A suitable commercially available product is Baytron(copyright) P of Bayer, an aqueous dispersion with 0.5% by weight of 3,4-polyethylenedioxythiophene (DEPT) and 0.8% by weight polystyrenesulfonate (PSS). Other preferred intrinsically electrically conductive polymers include conductive polyaniline, e.g. Versicon(copyright) (Allied Signal), a polyaniline with a conductivity of 2 to 4 S/cm or Ormecon(copyright) (Zipperling Kessler and Co.).
The cosmetic compositions according to the invention contain from 0.001 to 5 percent by weight, preferably 0.01 to 1 percent by weight, especially preferably from 0.02 to 0.5 percent by weight, of at least one intrinsically electrically conductive polymer, based on a total amount of the cosmetic composition present.
The cosmetic composition according to the invention is preferably an aqueous or aqueous/alcoholic composition. Lower alcohols suitable for cosmetic purposes having from one to four carbon atoms, e.g. ethanol and isopropanol, are preferred as the alcohols in the aqueous/alcoholic compositions of the invention. The aqueous or aqueous/alcoholic compositions according to the invention contain preferably from 40 to 95 percent by weight, especially preferably from 60 to 90 percent by weight, water. The alcohol content in the composition according to the invention is preferably from 1 to 30, especially preferably from 5 to 20, percent by weight. Also other water-soluble solvents or moisturizing agents, especially multivalent alcohols having from 2 to 4 carbon atoms, such as glycerol, ethylene glycols or propylene glycols, can be included in the cosmetic compositions according to the invention in an amount of from 0.1 to 10 percent by weight, preferably from 0.5 to 5 percent by weight.
At least one non-conductive film-forming synthetic or natural polymer can be contained in the compositions according to the invention in order to fix the electrically conductive polymeric compound on the hair. This additional polymer advantageously has nonionic, anionic or amphoteric character. Cationic polymers can be incompatible with Baytron(copyright) P. The additional non-conductive film-forming polymer is preferably present in an amount of from 0.5 to 10 percent by weight. Film-forming polymers are those polymers, which, when applied to the hair in an 0.1 to 5 percent by weight aqueous, alcoholic or aqueous-alcoholic solution are in a position to deposit a polymer film on the hair.
The composition according to the invention can also contain conventional cosmetic additive ingredients, e.g. perfume oils in an amount of preferably from 0.01 to 5 percent by weight; wetting agents or emulsifiers in an amount of preferably from 0.01 to 10 percent by weight; moisturizers; preservatives; bactericidal and fungicidal active-ingredients, such as 2,4,4-trichloro-2-hydroxy-diphenylether, parabene or methylchloroisothiazolinone, in an amount of from 0.01 to 1.0 percent by weight; buffer substances, such as sodium citrate or sodium phosphate, in an amount of form 0.1 to 1.0 percent by weigyht; dye substances, such as fluorescein sodium salt, in an amount of about 0.1 to 1.0 percent by weight; care ingredients, e.g. vegetable extracts, plant extracts, protein hydrolyzates, silk hydrolyzates, lanolin derivatives, in an amount of from 0.1 to 5 percent by weight; light-protective agents, anti-oxidants, radical trapping agents, anti-flaking agents, fatty alcohol, luster-imparting agents, vitamins and de-fatting agents, in an amount of from 0.01 to 10 percent by weight.
The composition according to the invention can have a pH in a pH range of from 2.0 to 9.5, preferably from 4.5 to less than 7 and especially preferably from 5.5 to 6.5. When the composition according to the invention is acidic or in the acid pH range, it can contain organic or inorganic acids, such as formic acid, tartaric acid, malic acid, maleic acid, fumaric acid, glyoxalic acid, pyrrolidone carboxylic acid, citric acid, lactic acid, sulfuric acid, acetic acid, hydrochloric acid, phosphoric acid, among others.
The composition according to the invention can be in the form of a lotion, an aerosol spray containing a propellant, a non-aerosol spray, an aerosol foam containing a propellant, a non-aerosol foam, a gel, a cream, an O/W emulsion, a W/O emulsion or a shampoo, in which the electrically conductive polymer is dissolved or dispersed. When the composition according to the invention has a low viscosity, it is particularly easily and satisfactorily distributed on the hair, also by spraying. The hair treatment composition according to the invention may then be combined with a suitable mechanically operated spraying device. By mechanically operated spraying device we mean those devices, which can produce a spray without using a propellant. Suitable mechanical spraying devices can, for example, include spray pumps or an elastic container provided with a spray valve, in which the composition according to the invention is filled under pressure. The composition according to the invention is dispensed from this latter elastic container by opening the spray valve because the elastic container contracts.
Hair and body cleansing compositions containing the electrically conductive polymer of the invention and at least one wash-active surfactant in an aqueous base are preferred embodiments of the invention. All those surfactants included for this purpose in shampoos or shower gels usually can be used as the wash-active surfactants. The surfactants can be present, alone or in a mixture, and are contained in an amount of preferable from 1 to 50 percent by weight, especially preferably from 1 to 30 percent by weight. Nonionic surfactants, amphoteric surfactants, zwitterionic surfactants and anionic surfactants are generally suitable.
Suitable anionic surfactants include, e.g. alkaline or alkaline earth salts of the C10- to C18-alkyl sulfates, the C10- to C18-alkyl sulfonates, the C10- to C18-alkyl benzyl sulfonates, the C10- to C18-xylyl sulfonates, the C10- to C18-alkyl sulfonates ethoxylated with from 1 to 10 ethylene oxide units, alpha-olefin sulfonates, sulfosuccinates, the ethoxylated sulfosuccinic acid semiesters of the general formula Rxe2x80x94(OCH2CH2)mxe2x80x94O2Cxe2x80x94CH2xe2x80x94CH(SO3M)xe2x80x94COOM, wherein R is a C10- to C18-alkyl group, M is an alkali or alkaline earth cation and m is a number from 1 to 10, especially sulfosuccinates, such as disodium laureth-3 sulfosuccinate, disodium PEG-5 lauryl citrate sulfosuccinate, disodium ricinolamido MEA-sulfosuccinate or disodium laurylamido MEA-sulfosuccinate and alkyl ether carboxylates of the general formula Rxe2x80x94(OCH2CH2)nxe2x80x94OCH2xe2x80x94COOM, wherein R is a C10- to C18-alkyl group, M is an alkali or alkaline earth cation and n is a number from 1 to 10, especially sodium laureth-6 carboxylate or sodium laureth-11 carboxylate. Preferably at least one alkali and alkaline earth salt of C10- to C18-alkyl ether sulfate ethoxylated with from 1 to 10 ethylene oxide units is present in the hair cleansing compositions of the invention.
Suitable nonionic surfactants include e.g. alkoxylated fatty alcohols with a high degree of alkoxylation, e.g. from 11 to 50, and alkoxylated fatty acid esters, alkoxylated partial glycerides of branched or unbranched, saturated or unsaturated C6- to C20-fatty acids, and with an alkoxylation degree of 11 to 400, e.g. polyethylene glycol (200) glyceryl palmitate, alkoxylated polyol esters, such as ethoxylated sugar esters, for example polyethylene glycol(120)methyl glucose dioleate and alkylpolyglucosides, such as coconut glucosides, lauryl gluycosides or decylglucosides. For example, ethoxylated lauryl alcohol, tetradecyl alcohol, cetyl alcohol, oleyl alcohol or stearyl alcohol, which are used alone or in mixtures with each other, as well as fatty alcohols of ethoxylated lanolin, are suitable as fatty alcohol ethoxylates. Examples of the fatty acid ester ethoxylates include, above all, castor oil ethoxylated with 25 ethylene oxide units with the INCI name PEG-25 hydrogenated castor oil, castor oil ethoxylated with 35 ethylene oxide units with the INCI name PEG-35 castor oil and castor oil ethoxylated with 40 ethylene oxide units with the INCI name PEG-40 hydrogenated castor oil. Furthermore the ethoxylated fatty acid sugar esters known as nonionic surfactants, especially ethoxylated sorbitan fatty acid ester, but not ethyoxylated surfactants in general, are suitable for use in the cosmetic preparations according to the invention. The suitable ethoxylated fatty acid sugar esters include those marketed under the trade names Tween(copyright) and Arlacel(copyright) by ICI surfactants and the alkyl-polyglycosides, which are marketed under the trade neames Plantaren(copyright) or Plantacare(copyright) by Henkel or under the trade name Oramix(copyright) by Seppic.
Suitable amphoteric surfactants include for example betaines, such as cocoamidopropylbetaine or lauryl betaine, sulfobetaines, such as cocoamidopropyl hydroxysultaine, glycinates, such as cocoamphoglycinate (INCI-name: sodium cocoamphoacetate) and diglycinates and propionates, such as cocoampho-propionate.
Additional preferred embodiments according to the invention are hair conditioning compositions and of course both rinse-out hair care compositions (Rinses, Treatments) and also leave-on hair products (leave-in products). These hair care compositions are usually based on O/W emulsions and contain water, at least one hydrophobic ingredient (especially at least one fatty alcohol) and a suitable emulsifier besides the intrinsically electrically conductive polymer compound.
The amount of hydrophobic material in the composition depends on the requirements for the end product that is prepared. Hair care compositions, for example, can contain from 5 to 30 percent by weight and hair cremes can contain up to about 50 percent by weight. The hydrophobic material in the oil phase of the hair care emulsions may be selected from the group consisting of water-insoluble waxes, fatty materials or oily materials. These ingredients can be liquid or solid at room temperature. Suitable waxes or waxy materials includes e.g. natural renewable waxes (insect, animal and plant waxes), fossil waxes (oil wax, brown coal wax, peat wax or ozokerite), synthetic waxes (Fischer-Tropsch wax, polyethylene wax or amide wax), high-melting paraffins, esters, fats, long-chain carboxylic acids or long-chain C10- to C22-alcohols. Also oil or oily materials, such as naturally occurring, renewable oils (plant oils or vegetable oils), synthetic oils, silicone oils, mineral oils, volatile oils, water-insoluble branched or linear aliphatic hydrocarbon material, linear or branched alcohols, especially liquid fatty alcohols and long-chain ethers or esters, wherein the above-named substances preferably have at least eight carbon atoms. Suitable hydrocarbon materials include, e.g., liquid paraffins, squalane or squalene. Furthermore esters of divalent and multivalent alcohols are suitable, especially plant triglycerides, such as olive oil, almond oil, peanut oil, sunflower seed oil and synthetic triglycerides, such as C8- to C10-trifatty acid glycerol esters or also jojoba oil. Suitable hydrophobic substances for the compositions according to the invention also include mono- or diesters of the formula R1xe2x80x94COOR2, R1xe2x80x94COOxe2x80x94R3OOR1 and R2xe2x80x94COOxe2x80x94R3xe2x80x94COOR2, wherein R1 represents a C8- to C22-alkyl group, R2 represents a C3- to C22-alkyl group and R3 represents a C2- to C16-alkyl groups. Naturally occurring monoesters or wax ester mixtures, e.g. present in jojoba oil or sperm oil, and branched primary alcohols, such as those known under the name guerbetaalcohols, are also suitable. The suitable hydrophobic substances also include additional substances, which are generally used in cosmetic compositions as turbidity inducing agents, especially those of formula R1xe2x80x94COOxe2x80x94(CHR4CHR5O)nxe2x80x94COR6, wherein R1 represents a C8- to C22-alkyl group, R4 and R5 represent hydrogen or methyl and R6 represents hydrogen or R1 and n is a number between 1 and 12, preferably 1, 2, 3 or 4. Ethylene glycol fatty acid diester or polyethylene glycol fatty acid diester present in solid form at room temperature is preferred.
The emulsion-form hair care composition according to the invention contains emulsifiers in an amount of from 0.5 to 30 percent by weight of the finished composition. Nonionic and anionic emulsifiers are suitable. Suitable emulsifiers include, for example, those described in xe2x80x9cInternational Cosmetic Ingredient Dictionary and Handbookxe2x80x9d, 7th Edition, Volume 2, in the section xe2x80x9cSurfactantsxe2x80x9d, especially in the sub-section xe2x80x9cSurfactantsxe2x80x94Emulsifying Agentsxe2x80x9d. Suitable nonionic emulsifiers include the above-named nonionic surfactants, especially ethoxylated fatty alcohols, ethoxylated nonylphenols, alkylpolyglycosides, fatty acid monoglycerides and diglycerides, ethoxylated and hydrogenated or non-hydrogenated castor oil, fatty acid alkanol amides and ethoxylated fatty acid esters. Suitable anionic emulsifiers can also be selected from the above-described anionic surfactants.
The conditioning composition according to the invention is employed in a method comprising distributing an amount sufficient for the desired conditioning effect in or on the wet or dry hair. The amount used depends on the abundance of the hair and usually amounts to from 1 to 25 g. In the preferred embodiment, the rinse product, the composition is rinsed out of the hair after an acting time of from 1 to 15 minutes. Subsequently the hair is thoroughly combed and shaped in a hairstyle. The hair is dried. Embodiments of this conditioning composition, which are leave-in products, are not rinsed out of the hair.
The following examples should illustrate the subject matter of the invention.

Cosmetic compositions containing electrically conductive polymers