The invention provides hair styling compositions, for example creams, gels and especially aerosol hair styling mousses. The compositions contain a cross-linked silicone, such as an emulsion of cross-linked dimethiconol gum, and a cationic hair styling polymer having a cationic charge density of at least 1 meq/g. The compositions provide excellent styling as well as sensory feel.

The present invention relates to hair styling compositions, for example creams, gels and especially aerosol hair styling mousse compositions, which contain cross-linked silicone and which deliver excellent styling as well as sensory feel.
Style creation products such as hair styling mousses provide human hair with a temporary set which can be removed by water or by shampooing, and function by applying a thin film of a resin or gum onto the hair to adhere adjacent hairs together so that they retain the particular shape or configuration at the time of application.
EP 818 190 describes how an emulsion polymerised silicone material having a particular, defined level of cross-linking, and which is cross-linked in emulsion form can be incorporated into a hair styling composition, such as a mousse, gel or cream, to give a formulation which delivers excellent style creation and longevity, whilst leaving the hair soft and natural. An important feature of these systems is the phase behaviour of the silicone, which is said to form a separate high viscosity aggregated phase in the composition. This phase behaviour is considered to be key to effective style creation.
A problem with xe2x80x9caggregatingxe2x80x9d systems as described in EP 818 190 is that they can tend to gel and form lumps under conditions of prolonged, high temperature storage.
One solution to this problem is to use a nonionic surfactant having an HLB value of at least 14.5, such as those nonionic surfactants of general formula R(EO)x H, where R represents a straight or branched chain alkyl group having an average carbon chain length of 12-18 carbon atoms and x ranges from 30 to 50.
However, some of the above-described nonionic surfactants form particularly stable foams. In the case of hair styling mousse product forms, consumers generally prefer that the foam generated collapses after less than five minutes after discharge, for ease of spreading on the hair. In such instances, this necessitates the use of anti-foaming ingredients in the composition to reduce foaming to a consumer-acceptable level.
Surprisingly, it has now been found that by the use of certain cationic polymers of specified cationic charge density, the silicone materials as described in EP 818 190 may be formulated into systems which do not form a separate high viscosity aggregated phase and yet nevertheless deliver effective style creation. Advantageously, it is not necessary to use high HLB nonionic surfactants with these systems, which allows the formulator greater freedom to formulate the a composition with the desired foam properties.
The present invention provides a hair styling composition comprising:
(i) from 0.1% to 10% by weight, based on total weight, of a cross-linked silicone polymer, in which the percentage of branched monomer units in the silicone polymer is from 0.05% to 10%;
(ii) from 0.1% to 10% by weight, based on total weight, of a cationic hair styling polymer having a cationic charge density of at least 1 meq/g;
(iii) from 0.01% to 5% by weight, based on total weight, f a surfactant;
(iv) water; and
(v) from 0% to 30% by weight, based on total weight, of an aerosol propellant.
The hair styling composition of the invention comprises a cross-linked silicone polymer (i). The silicone polymer will generally be insoluble in the aqueous medium of the hair styling composition and so be present in an emulsified form, with the silicone polymer present as dispersed particles.
Suitable cross-linked silicone polymers include cross-linked polydiorganosiloxanes, in particular cross-linked polydimethylsiloxanes (also termed cross-linked dimethicone). Also suitable for use in hair treatment compositions of the invention are cross-linked polydimethyl siloxanes having hydroxyl end groups (also termed cross-linked dimethiconol).
The cross-linked silicone polymer is present in compositions of the invention in an amount from 0.1% to 10% by weight based on the total weight of the composition, more preferably from 0.2% to 6% by weight, most preferably from 0.5 to 5% by weight.
The degree of cross-linking of the cross-linked silicone polymer can be measured as the percentage of branched monomer units in the silicone polymer. This value may suitably range from about 0.001% to about 35%, preferably 0.002 to 10%, more preferably 0.003 to 10%, optimally 0.004% to 2%. Increasing cross-linking is found to improve hair styling benefits but also to reduce conditioning performance somewhat, so compromise levels must be selected with properties optimised to suit consumer preferences in different cases. Good overall performance has been obtained with about 0.6% degree of cross-linking (i.e., percentage of branched monomer units)
Cross linking of the silicone polymer may for example be introduced in situ during the polymerisation process which forms the silicone polymer from its constituent monomer units, through the inclusion of the required amount of trifunctional and tetrafunctional silane monomer units, for example, those of formula R Si (OH)3 wherein R represents an alkyl, alkenyl (e.g. vinyl), alkaryl, aralkyl or aryl (e.g. phenyl) group, preferably methyl.
Alternatively, other types of silicone cross-linking chemistry may be used to produce suitable cross-linked silicone polymers for use in the invention. The cross-linking agents employed in such methods may be organosilicon cross-linking agents, for example as listed in EP 0 473 039, or non-silicone cross-linking agents, for which a representative example is the cross-linked silicone polymer described in U.S. Pat. No. 5,654,362. The cross linker used here is an alpha, omega aliphatic diene of the following structure: CH2xe2x95x90CH(CH2)XCHxe2x95x90CH2, where X ranges from 1-20. A gel is formed by cross-linking and addition of Is-H across double bonds in the alpha, omega-diene.
Further examples of suitable cross-linked silicone polymers for use in the invention include the materials DC 3-2365, ex Dow Corning, and the silicone-urethane copolymer Polyderm PPI-SI-100, ex Akzo Incorporated, Matawan, N.J.
The especially preferred cross-linked silicone polymers for use in compositions of the invention are silicone gums having a slight degree of cross-linking as described in WO 96/31188. These materials can impart fullness, body and volume to hair, as well as good wet and dry conditioning.
Various methods of making emulsions of particles of cross-linked silicone polymers for use in the invention are available and are well known and documented in the art. For example, emulsions may be prepared by high shear mechanical mixing of the silicone polymer and water, or by emulsifying the silicone polymer with water and an emulsifier (mixing the silicone polymer into a heated solution of the emulsifier for instance), or by a combination of mechanical and chemical emulsification. For certain materials such as the cross-linked silicone polymer described in U.S. Pat. No. 5,654,362, it may be advisable to mix them first with a hydrophilic or hydrophobic diluent such as PPG-2 myristyl ether propionate or cyclomethicone, in order to facilitate the subsequent emulsification step.
A particularly suitable technique for preparation of emulsions of particles of silicone polymers is emulsion polymerisation. Emulsion polymerised silicone polymers as such are described in U.S. Pat. No. 2,891,820 (Hyde), U.S. Pat. No. 3,294,725 (Findlay) and U.S. Pat. No. 3,360,491 (Axon).
Suitable emulsion polymerised cross-linked silicone polymers are commercially available or can be readily made using conventional techniques well known to those skilled in the art.
Suitable cross-linked silicone polymer emulsions for use in the invention are commercially available in a pre-emulsified form. This is particularly preferred since the pre-formed emulsion can be incorporated into the hair treatment composition by simple mixing. Pre-formed emulsions are available from suppliers of silicone oils such as Dow Corning, General Electric, Union Carbide, Wacker Chemie, Shin Etsu, Toshiba, Toyo Beauty Co, and Toray Silicone Co.
The preferred cross-linked silicone gums for use in compositions of the invention are also available in a pre-emulsified form, which is advantageous for ease of formulation. An especially preferred example is the material available from Dow Corning as DC X2-1787, which is an emulsion of cross-linked dimethiconol gum in which the viscosity of the silicone polymer itself is about 2xc3x97107 cst.
When the cross-linked silicone polymer is incorporated as a pre-formed emulsion as described above, the exact quantity of emulsion will of course depend on the concentration of the emulsion, and should be selected to give the desired quantity of silicone polymer in the final composition.
The cationic hair styling polymer (ii) employed in compositions of the present invention should be capable of forming a film and holding the hair of the user in place. It is present in compositions of the invention in an amount from 0.1% to 10% by weight based on the total weight of the composition, more preferably from 0.1% to 5% by weight, most preferably from 0.2 to 4% by weight.
Hair styling polymers are well known articles of commerce and many such polymers are available commercially which contain functional groups which render the polymers cationic, anionic, amphoteric or nonionic in character.
As used herein the xe2x80x9ccharge densityxe2x80x9d of the cationic hair styling polymer is defined as the number of cationic sites per polymer gram atomic weight (molecular weight), and is expressed in terms of meq/gram of cationic charge (meq/g). The charge density can be controlled and adjusted in accordance with techniques well known in the art. Those skilled in the art will recognise that the charge density of amino-containing polymers may vary depending upon pH and the isoelectric point of the amino groups. In general, adjustment of the proportions of amine or quaternary ammonium moieties in the polymer, as well as pH of the composition in the case of the amines, will affect the charge density. Cationic charge density of the polymer can be determined according to the Kjeldahl Method.
The cationic hair styling polymers used herein have a cationic charge density of 1.0 meq/g and higher. Preferably the polymer has a charge density of at least 2.0 meq/g. more preferably the polymer has a charge density of at least 2.5 meq/g, such as from 2.8 to 7.5 meq/g, ideally from 2.8 to 7.0 meq/g. The charge density should be within the above limits at the pH of intended use, which will in general be from about pH 3 to about pH 9, usually from about pH 4 to about pH 8.
Examples of suitable cationic hair styling polymers are copolymers of amino-functional acrylate monomers (such as lower alkylaminoalkyl acrylate) or methacrylate monomers (such as dimethylaminoethyl methacrylate) with compatible monomers such as N-vinylpyrrolidone, vinyl caprolactam, or alkyl methacrylates (such as methyl methacrylate and ethyl methacrylate) and alkyl acrylates (such as ethyl acrylate and n-butyl acrylate).
Other suitable cationic hair styling polymers include those cationic polymers containing or derived from quaternary ammonium monomers having cyclic cationic nitrogen-containing rings (such as alkyl vinyl imidazolium). The alkyl portions of these monomers are preferably lower alkyls such as the C1 to C3 alkyls, more preferably C1 and C2 alkyls.
Preferred cationic hair styling polymers include methylvinylimidazolium chloride/vinylpyrrolidone copolymers (having the CTFA designation Polyquaternium-16), provided such copolymers have a cationic charge density of 1.0 meq/g and higher, as described above. Examples include copolymers of this type in which the weight percentage of methylvinylimidazolium chloride monomer in the copolymer is at least 10%, preferably at least 25%, most preferably at least 35% by weight based on total weight of the copolymer. These materials are commercially available from BASF AG under the LUVIQUAT tradename, as LUVIQUAT FC 370, LUVIQUAT FC 550, LUVIQUAT HM 552 and LUVIQUAT FC 905.
Also suitable are vinylcaprolactam/vinylpyrrolidone/vinylimidazolium copolymers (having the CTFA designation Polyquaternium 46) provided such copolymers have a cationic charge density of 1.0 meq/g and higher, as described above. Examples include copolymers of this type which have a vinylimidazolium monomer content of at least 25% by weight based on total weight of the copolymer. An example copolymer would have weight percentages of vinylcaprolactam monomers and vinylpyrrolidone monomers and vinylimidazolium monomers of 40%, 30% and 30% respectively, by weight based on total weight of the copolymer. Preferably, the vinylimidazolium monomer content is at least 50%, ideally around 65% by weight based on total weight of the copolymer.
Copolymers of methoimidazolinium and vinylpyrrolidone would be also be suitable (having the CTFA designation Polyquaternium 11) provided such copolymers have a cationic charge density of 1.0 meq/g and higher, as described above. Examples are copolymers of this type in which the weight percentage of methoimidazolinium monomer is at least 10%, preferably at least 33%, most preferably at least 50% by weight based on total weight of the copolymer.
In addition to the cross-linked silicone polymer and the hair styling polymer, the hair styling composition of the invention also includes a surfactant (iii) in an amount ranging from 0.01% to 5%, preferably from 0.01% to 1%, most preferably from 0.02% to 0.8% by weight based on total weight.
Surfactants are generally classified as nonionic, anionic, cationic, amphoteric or zwitterionic according to their ionic behaviour in aqueous solution.
Examples of nonionic surfactants are condensation products of aliphatic (C8-C18) primary or secondary linear or branched chain alcohols or phenols with alkylene oxides, usually ethylene oxide and generally having from 6 to 30 ethylene oxide groups. Other suitable nonionics include esters of sorbitol, esters of sorbitan anhydrides, esters of propylene glycol, fatty acid esters of polyethylene glycol, fatty acid esters of polypropylene glycol, ethoxylated esters and polyoxyethylene fatty ether phosphates.
Examples of anionic surfactants are the alkyl sulphates, alkyl ether sulphates, alkaryl sulphonates, alkanoyl isethionates, alkyl succinates, alkyl sulphosuccinates, N-alkoyl sarcosinates, alkyl phosphates, alkyl ether phosphates, alkyl ether carboxylates, and alpha-olefin sulphonates, especially their sodium, magnesium ammonium and mono-, di- and triethanolamine salts. The alkyl and acyl groups generally contain from 8 to 18 carbon atoms and may be unsaturated. The alkyl ether sulphates, alkyl ether phosphates and alkyl ether carboxylates may contain from one to 10 ethylene oxide or propylene oxide units per molecule, and preferably contain 2 to 3 ethylene oxide units per molecule.
Examples of cationic surfactants are cetyltrimethylammonium chloride, behenyltrimethylammonium chloride, cetylpyridinium chloride, tetramethylammonium chloride, tetraethylammonium chloride, octyltrimethylammonium chloride, dodecyltrimethylammonium chloride, hexadecyltrimethylammonium chloride, octyldimethylbenzylammonium chloride, decyldimethylbenzylammonium chloride, stearyldimethylbenzylammonium chloride, didodecyldimethylammonium chloride, dioctadecyldimethylammonium chloride, tallowtrimethylammonium chloride, cocotrimethylammonium chloride, (and the corresponding hydroxides thereof), and those materials having the CTFA designations Quaternium-5, Quaternium-31 and Quaternium-18.
Examples of amphoteric and zwitterionic surfactants include alkyl amine oxides, alkyl betaines, alkyl amidopropyl betaines, alkyl sulphobetaines (sultaines), alkyl glycinates, alkyl carboxyglycinates, alkyl amphopropionates, alkylamphoglycinates alkyl amidopropyl hydroxysultaines, acyl taurates and acyl glutamates, wherein the alkyl and acyl groups have from 8 to 19 carbon atoms.
The surfactant in compositions of the invention is most preferably a nonionic surfactant. Such a nonionic surfactant will generally have an HLB (hydrophilic-lipophilic balance) value of about 3 to about 20. The HLB value per se and how it is calculated is described in J.Soc.cosmet.Chem., 1949,1,311. For a given nonionic surfactant, the HLB value represents the weight per cent of the hydrophilic content of the molecule divided by a factor of five.
Exemplary nonionic surfactants having an HLB value of less than 10 include laureth-2, laureth-3, laureth-4, PEG-3 castor oil, an ethoxylated nonylphenol, ethoxylated octylphenol, ethoxylated dodecylphenol or ethoxylated fatty (C6 to C22) alcohol having less than 9 ethylene oxide moieties, PEG 600 dioleate, PEG 400 dioleate, and mixtures thereof.
Exemplary nonionic surfactants having an HLB value of 10 or greater include methyl gluceth-20, methyl gluceth-10, PEG-20 methyl glucose distearate, PEG-20 methyl glucose sesquistearate, PEG-200 castor oil, C11-15 pareth-20, ceteth-8, ceteth-12, dodoxynol-12, laureth-15, PEG-20 castor oil, polysorbate 20, steareth-20, polyoxyethylene-10 cetyl ether, polyoxyethylene-10 stearyl ether, polyoxyethylene-20 cetyl ether, polyoxyethylene-21 stearyl ether, polyoxyethylene-10 oleyl ether, polyoxyethylene-20 oleyl ether, an ethoxylated nonylphenol, ethoxylated octylphenol, ethoxylated dodecylphenol or ethoxylated fatty (C6 to C22) alcohol including at least 9 ethylene oxide moieties, polyoxyethylene-20 isohexadecyl ether, dimethicone copolyol, polyoxyethylene-23 glycerol laurate, polyoxyethylene-20 glyceryl stearate, PPG-10 methyl glucose ether, PPG-20 methyl glucose ether, polyoxyethylene-80 castor oil, polyoxyethylene-15 tridecyl ether, polyoxyethylene-6 tridecyl ether, and mixtures thereof.
Preferred nonionic surfactants for use in compositions of the invention are polysorbate 20, polysorbate 80, ethoxylated nonylphenol, steareth-20, cetosteareth-20, steareth-30, cetosteareth-30, steareth-50, and cetosteareth-50.
Surfactants selected from anionic, cationic, amphoteric and zwitterionic surfactants may suitably be used in conjunction with any of the above nonionic surfactants, to improve, for example, foaming power and/or foam stability.
Compositions of the present invention will also include water, preferably distilled or deionised, as a solvent or carrier for the polymers and other components. Water will typically be present in amounts ranging from 30% to 98%, preferably from 60% to 95% by weight based on total weight.
Alcohol may optionally be employed as a co-solvent in compositions of the invention as this can enhance the performance of the styling composition. A suitable alcohol is an aliphatic straight or branched chain monohydric alcohol having 2 to about 4 carbon atoms. Isopropanol and especially ethanol are preferred. A suitable level for the alcohol is up to 20%, preferably from 5% to 15%, by weight based on total weight.
Compositions of the invention may suitably be in aerosol form. A particularly preferred product form is an aerosol hair mousse. Aerosol hair mousse compositions are emitted from the aerosol container as a foam which is then typically worked through the hair with fingers or a hair styling tool and either left on the hair or rinsed out.
Aerosol-form compositions of the invention will include an aerosol propellant (v) which serves to expel the other materials from the container, and forms the mousse character in mousse compositions. The aerosol propellant included in styling compositions of the present invention can be any liquefiable gas conventionally used for aerosol containers. Examples of suitable propellants include dimethyl ether and hydrocarbon propellants such as propane, n-butane and isobutane. The propellants may be used singly or admixed. Water insoluble propellants, especially hydrocarbons, are preferred because they form emulsion droplets on agitation and create suitable mousse foam densities.
The amount of the propellant used is governed by normal factors well known in the aerosol art. For mousses the level of propellant is generally up to 30%, preferably from 2% to 30%, most preferably from 3 to 15% by weight based on total weight of the composition. If a propellant such as dimethyl ether includes a vapour pressure suppressant (e.g. trichloroethane or dichloromethane), for weight percentage calculations, the amount of suppressant is included as part of the propellant.
The method of preparing aerosol hair styling mousse compositions according to the invention follows conventional aerosol filling procedures. The composition ingredients (not including the propellant) are charged into a suitable pressurisable container which is sealed and then charged with the propellant according to conventional techniques.
Compositions of the invention may also take a non-foaming product form, such as a hair styling cream or gel. Such a cream or gel will include a structurant or thickener, typically at a level of from 0.1% to 10%, preferably 0.5% to 3% by weight based on total weight.
Examples of suitable structurants or thickeners are polymeric thickeners such as carboxyvinyl polymers. A carboxyvinyl polymer is an interpolymer of a monomeric mixture comprising a monomeric olefinically unsaturated carboxylic acid, and from about 0.01% to about 10% by weight of the total monomers of a polyether of a polyhydric alcohol. Carboxyvinyl polymers are substantially insoluble in liquid, volatile organic hydrocarbons and are dimensionally stable on exposure to air. Suitably the molecular weight of the carboxyvinyl polymer is at least 750,000, preferably at least 1,250,000, most preferably at least 3,000,000. Preferred carboxyvinyl polymers are copolymers of acrylic acid cross-linked with polyallylsucrose as described in U.S. Pat. No. 2,798,053. These polymers are provided by B.F.Goodrich Company as, for example, CARBOPOL 934, 940, 941 and 980. Other materials that can also be used as structurants or thickeners include those that can impart a gel-like viscosity to the composition, such as water soluble or colloidally water soluble polymers like cellulose ethers (e.g. methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose and carboxymethylcellulose), guar gum, sodium alginate, gum arabic, xanthan gum, polyvinyl alcohol, polyvinyl pyrrolidone,hydroxypropyl guar gum, starch and starch derivatives, and other thickeners, viscosity modifiers, gelling agents, etc. It is also possible to use inorganic thickeners such as bentonite or laponite clays.
The hair styling compositions of the invention can contain a variety of nonessential, optional components suitable for rendering the compositions more aesthetically acceptable or to aid use, including discharge from the container, of the product. Such conventional optional ingredients are well known to those skilled in the art, e.g. preservatives such as benzyl alcohol, methyl paraben, propyl paraben and imidazolidinyl urea, fatty alcohols such as cetearyl alcohol, cetyl alcohol and stearyl alcohol, pH adjusting agents such as citric acid, succinic acid, sodium hydroxide and triethanolamine, colouring agents such as any of the FDandC or DandC dyes, perfume oils, chelating agents such as ethylenediamine tetraacetic acid, and polymer plasticising agents such as glycerin and propylene glycol.

Unilever Home and Personal Care USA, division of Conopco, Inc.


The invention relates to a novel process for the preparation of polycondensate solutions based on polyamidoamine/epichlorohydrin resins that gives products having a very low content of organic chlorine compounds, in particular a 1,3-dichlorophenol-2-propanol content of  less than 0.1%, in combination with high activity and good shelf-life.

The present invention relates to a novel process for the preparation of polycondensate solutions based on polyamidoamine/epichlorohydrin resins having a 1,3-dichloro-2-propanol content of  less than 0.1%.
Reaction products of polyamidoamines and/or polyamines with epichlorohydrin have long been used for imparting wet strength to paper.
The products contain organic chlorine compounds, some of which are polymer-bound while the others consist of low molecular weight secondary components which are formed by undesired secondary reactions of the epichlorohydrin with water and chloride ions, preferably in the acidic range, e.g. 1,3-dichloro-2-propanol (DCP) and 1-chloro-2,3-propanediol (CPD).
These low molecular weight components, some of which are adsorbed only slightly by the cellulose fibers in the production of papers having wet strength, finally enter the wastewater of the paper mill, where they are detected as AOX (adsorbable organic halogen content) (DIN 38409). In recent years, the authorities have imposed taxes according to the AOX emissions and have also set limits for the AOX pollution of the wastewater which are to be complied with, so that a reduction of the AOX pollution was required for epichlorohydrin resins as a source of the AOX pollution.
A large number of proposed solutions for reducing the organic chlorine content of the polycondensates are already known.
Thus, for example, an aftertreatment of the polycondensate with a base is carried out in the European Patent Applications EP-A 282 862 and EP-A 332 967 and with an inorganic base and an organic mono- or polyamine or with ammonia in EP-A 512 423.
EP-A 0 349 935 describes polycondensates which contain polyamines and alkanolamines as amine component and which are likewise subjected to a base aftertreatment for reducing the organic chlorine content.
In these processes, it is true that the organic chlorine content is substantially reduced. However, they are all very complicated since a repeated change in the pH is required and in all cases the final addition of acid is required, which is intended to stabilize the polycondensate in the acidic pH range. The result is a relatively high electrolyte content of the commercial product, which adversely affects the shelf-life and can cause corrosion problems during use. If it is necessary to impart sufficiently high wet strength to paper, it is moreover necessary in this process to use relatively large amounts of xe2x89xa71.0 mole of epichlorohydrin per base nitrogen. Although it is possible also to employ smaller amounts of epichlorohydrin, a substantial loss of the wet strength activity must then be accepted.
Since products having a high DCP content may constitute a health risk, labeling of commercial products based on epichlorohydrin resins was demanded in Germany when the DCP content exceeds a value of 0.1%. For this reason, the manufacturers of wet strength agents based on epichlorohydrin had to make considerable additional effort to fall below these limits, to avoid the levies and to formulate the product to be toxicologically safe.
EP 469 891 describes, for example, a process for the reaction of polyamidoamine with epichlorohydrin at temperatures of not more than 60xc2x0 C. to a conversion of 70-100%, addition of an acid and further reaction, a reduction of the organically bound chlorine by at least 10% being achieved. Here, the acid is added during the condensation itself and has the function of reducing the rate of the condensation in the final stage.
Furthermore, processes are known (cf. for example EP-A 488 767, EP-A 717 146, EP-A 374 938, U.S. Pat. No. 5 239 047 and U.S. Pat. No. 5 364 927) which aim at reducing the content of organic chlorine and DCP in the polycondensate by a special reaction procedure and a reduction in the molar amount of epichlorohydrin used per mole of base nitrogen.
EP-A 540 943 describes a process for the preparation of polycondensates by reacting polyamidoamine and/or polyamine with epichlorohydrin, an inert gas being passed through the reaction mixture before and optionally also during the partial crosslinking.
EP-A 320 121 describes a process for the stabilization of aqueous, at least 15% strength solutions of a polyamide/epichlorohydrin resin to gelling and viscosity reduction, an aqueous mixture of a weak and a strong acid being added to said resin solution in amounts of from 0.6 to 1.2 mmol of protons per g of solid resin. The molar ratio of the weak acid to the strong acid is from 0.5 to 10, preferably from 2.0 to 4.0 and particularly preferably from 3.0 to 3.1 (relative to protons). In this process the pH is generally brought to from 3 to 4.2, preferably to from 3.2 to 3.4. This process is preferably applied to resins which are prepared by an addition reaction of from 1.0 to 1.7 mol of epichlorohydrin per secondary amino-N of the polyamide at temperatures of from 45 to 70xc2x0 C. In the case of smaller amounts of epichlorohydrin, a loss of activity is to be expected; in the case of a larger amount of epichlorohydrin, stability problems are envisaged. No information is given about the content of DCP.
As shown by the large number of citations mentioned as prior art, various experiments were carried out in the past to formulate optimum polyamidoamine/epichlorohydrin resins. The desired parameters of satisfactory ecological behavior through a low content of organic chlorine compounds (AOX, DCP, CPD), high wet strength and good shelf-life in combination with an economically advantageous preparation process without complicated additional steps could not be simultaneously achieved since some of them require contradictory measures in the preparation process.
In many cases, in particular an adequate shelf-life also remained a problem which usually manifested itself after a short storage time, depending on the preparation process and on the formulation as well as on the storage conditions, in an undesirable change in the physical data, for example in an increase in the pH, an increase or decrease in the viscosity, increasing discoloration and a loss of activity.
Thus, it was furthermore the object to provide an improved simple process for the preparation of polycondensate solutions having a very low content of organic chlorine compounds, in particular of 1,3-dichloro-2-propanol, high wet strength activity and a good shelf-life.
The process according to the invention achieves this object by permitting the preparation of polycondensate solutions based on polyamidoamine/epichlorohydrin resins having a very low content of organic chlorine compounds, in particular of 1,3-dichloro-2-propanol, in particular a content of 1,3-dichloro-2-propanol of  less than 0.1%, high activity and a good shelf-life. The present process for the preparation of polycondensate solutions is characterized by
a) reaction of a1) at least one basic polyamidoamine and/or at least one polyamine in the form of a 10-50% strength solution with a2) epichlorohydrin at 10-25xc2x0 C., the molar ratio of epichlorohydrin to base-N in al) being from 0.5 to 0.85;
b) subsequent further reaction at 10-25xc2x0 C. to an epichlorohydrin conversion of not more than 90-99%;
c) subsequent reaction of the product from b) with further solution al) for completion of the epichlorohydrin conversion in a molar ratio of the base-N contained in solution a1) to epichlorohydrin of from 1:1 to 1.2:1, the pH being kept above 6;
d) heating to 30-70xc2x0 C. until the viscosity of a 15% strength solution is 30-100 mPas at 25xc2x0 C., and
e) reaction of the product from d) with formic acid and/or sulfuric acid, the pH being brought to from 2.0 to 3.0.
The process according to the invention is distinguished by technically simple conditions and requires no complicated additional steps, like many of the processes described above. Surprisingly, the polycondensates prepared by this process nevertheless have both a very low DCP content of  less than 0.1% and a wet strength activity improved compared with known processes, as well as an improved shelf-life.
The polyamidoamine stated under a1) is prepared by reacting an aliphatic dicarboxylic acid with a polyalkylenepolyamine in a molar ratio of from 1.0:1 to 1:1.2.
Polyalkylenepolyamines which contain at least two amino groups capable of amide formation and at least one further secondary or tertiary amino group are suitable. Particularly suitable polyamines are diethylenetriamine, triethylenetetramine, tetraethylenepentamine, pentaethylenehexamine, etc. and N-methyl-bis-(aminopropyl)amine, bis-hexamethylenetriamine, N-aminoethylpiperazine or bis-aminoethylpiperazine. In addition, diamines, such as ethylenediamine, diaminopropane and 1,6-diaminohexane may also be concomitantly used in a small amount. A particularly preferred polyalkylenepolyamine is diethylenetriamine.
Saturated dicarboxylic acids having 2 to 12 C atoms or their functional derivatives, such as anhydrides, esters or monoesters, are suitable as the aliphatic dicarboxylic acid. Examples are malonic acid, succinic acid, glutaric acid, adipic acid and sebacic acid, their dimethyl or diethyl esters and also corresponding mixtures. Adipic acid is particularly preferred. The concomitant use of (o-aminocarboxylic acids containing 3-6 C atoms, such as aminocaproic acid, or their lactams, such as, for example, xcex5-caprolactam, is also possible.
The reaction of the aliphatic dicarboxylic acid with polyalkylenepolyamine to give a polyamidoamine is carried out in a molar ratio of from 1:1.0 to 1:1.2 at temperatures of 120-200xc2x0 C. while distilling off water (melt polymerization). Usually, the mixture of said components is first heated to temperatures between 100 and 150xc2x0 C. The low-viscosity melt obtained is slowly heated to not more than 200xc2x0 C. after not more than 3 hours at atmospheric pressure, the resulting water of reaction being distilled off. The process can also be carried out under pressure.
In order to avoid discolorations of the reaction product, it is expedient to effect condensation in the absence of oxygen. Distillation is continued until at least 98% of the theoretical amount of water have been removed, i.e. 1 mol of water per mol of carboxyl group of the dicarboxylic acid.
After the end of the melt polycondensation, dilution to a solids content of from 20 to 60%, preferably 40-55%, is effected by adding water, since the polyamidoamines can be stored and further processed more easily in this dilute form. The viscosity of a 50% strength solution should be from 200 to 800 nPas at 25xc2x0 C. The base equivalent weight of a 50% strength solution of a polyamidoamine a1) suitable for the process according to the invention, determined by titration by known methods, is preferably 300-500 g/eq.
The basic polyamidoamines described above can be used in an individual mixture or in any desired mixture with one another or in any desired mixture with polyamines according to al). Suitable polyamines are compounds of the formula (I)
in which
x and y independently of one another represent 0 or 1
m and p independently of one another represent from 0 to 5
R6 and R7 independently of one another represent H or methyl
n represents from 0 to 5,
R1, R2 and R3 independently of one another represent H, methyl, ethyl, hydroxyethyl, hydroxypropyl or a radical of the formula (II)
xe2x80x83wherein
R8 represents H, methyl or ethyl,
R6 and x have the abovementioned meaning and
s and t independently of one another represent from 0 to 3,
and
R5 and R4 independently of one another represent H, methyl, ethyl, hydroxyethyl, hydroxypropyl, but at least one radical R4 or R5 represents H, or
R4 and R5 together represent a group of the formula xe2x80x94CH2CH2NHCH2CH2xe2x80x94,
and,
where m, n and p represent zero, at least one of the substituents R3, R4 and R5 is different from hydrogen.
Examples of particularly preferred polyamines of the formula (I) are: diethylenetriamine, triethylenetetramine, tetraethylenepentamine, pentaethylenehexamine, hexaethyleneheptamine, dipropylenetriamine, dihexamethylenetriamine, N-methyl-bis(3-aminopropyl)amine, tris(2-aminoethyl)amine, piperazine, bis(piperazinyl)ethane, N-(2-aminoethyl)-piperazine, bisaminoethylpiperazine, bisaminopropylpiperazine.
Of course, polyamine mixtures may also be used instead of the pure polyamines.
The use of a pure polyamidoamine obtained from adipic acid and diethylenetriamine is particularly preferred. The metering of the epichlorohydrin is effected in 0.5-5 hours at temperatures of 10-25xc2x0 C., preferably continuously for better control of the exothermic addition reaction, optionally also discontinuously or batchwise.
The further reaction of the epichlorohydrin is then effected in stage b) within 4-10 hours at 10-25xc2x0 C. until an epichlorohydrin conversion of 90-99%, preferably 95-99%, is reached. At higher temperatures, undesired byproducts, such as DCP and CPD, form to an increasing extent. At lower temperatures, the speed of the addition reaction of the epichlorohydrin with the polyamidoamine is too low so that uneconomically long reaction times are required and the desired epichlorohydrin conversion is not reached.
Batch reactors have proved useful as reactors for the addition reaction of the epichlorohydrin with the polyamidoamine in stages a) and b). Alternatively, continuous apparatuses, such as multistage reactors and tubular reactors, may also be used for optimum utilization of the epichlorohydrin, for avoiding back-mixing and for good heat removal and temperature control.
The product obtained in stage b) is then reacted in stage c) with further solution a1) for reaction of the remaining, unconverted epichlorohydrin a2) amounting to not more than 10%, preferably 1-5%, of the amount of epichlorohydrin a2) used, the molar ratio of the base-N contained in solution a1) to epichlorohydrin a2) being from 1:1 to 1.2:1. In this reaction, the pH is kept above 6, preferably above 7, with the result that undesired secondary reactions are suppressed. As a result of this measure, the reaction time is shortened and the content of organically bound chlorine and DCP and CPD is further reduced. Optionally, the further addition of solution a1) may also be effected at the beginning of the heating phase of the following stage d). However, the addition before the heating stage is more advantageous.
In stage d), the product obtained, optionally after dilution with water to 10-25%, is heated to temperatures of from 30 to 70xc2x0 C., preferably 50-60xc2x0 C., and kept at this temperature for from 2 to 6 hours. The condensation or partial crosslinking of the reaction product formed as an intermediate takes place here and is carried out until the viscosity of a 15% strength solution is from 30 to 100 mPas at 25xc2x0 C. At a lower viscosity, a loss of wet strength activity is to be expected; at higher viscosity, the handling, for example pumpability and meterability of the product, becomes more difficult and the shelf-life is reduced because premature swelling is possible, making the product unusable.
After the desired final viscosity from 30 to 100 mPas has been reached in stage d), the product is reacted in stage e) with formic acid and/or sulfuric acid, the pH being brought to from 2.0 to 3.0. The further crosslinking is stopped and the product is stabilized to a further viscosity increase. The concomitant use of further acids, such as nitric acid, phosphoric acid, acetic acid or also acetic anhydride, propionic acid, citric acid, phosphonobutanetricarboxylic acid, malonic acid, tartaric acid, adipic acid, glutaric acid, etc., is possible. The use of halogen-containing acids, such as hydrochloric acid, is less preferred. A combination of sulfuric acid and formic acid is preferably used and can be added as a mixture or in succession in any desired order. Better constancy of the viscosity and of the pH is achieved in particular by using formic acid, so that the shelf-life of the commercial product is decisively improved.
Since the pH is to be regarded as a target parameter, it is not possible to establish the amounts of acid exactly. For example, amounts of from 0.3 to 6 mol of acid (calculated relative to proton content) per kg of solid resin are however usual. From 0.5 to 3 mol of acid, relative to solid resin, are preferably used.
The molar ratio of formic acid to sulfuric acid (relative to proton content) may be brought to any desired values between 0.2 and 10. A molar ratio of from 1.0 to 2.5 is preferred.
The pH is brought to from 2.0 to 3.0, preferably to from 2.4 to 2.9, by adding the abovementioned acids. Lower pH values lead to a decrease in the viscosity with loss of activity after a relatively long storage time. At a pH above 3.0, an increase in the viscosity, possibly up to swelling of the product, is to be expected, so that a desired shelf-life of from 3 to 6 months cannot reliably be reached.
If required, the solids concentration is brought with water to the desired final concentration of, for example, from 10 to 30%, preferably from 12 to 20%, simultaneously with, before or after the acid addition in stage e).
In order to lighten the hue of the polycondensate solution prepared according to the invention and to avoid the undesired further discoloration occurring under unfavorable storage conditions, it is advantageous to add small amounts of a reducing sulfur compound to the polycondensate solution after the end of stage e). In particular, sodium disulfite, sodium bisulfite, sodium dithionite and sodium formaldehyde sulfoxylate are suitable. As a rule, it is sufficient to use amounts of from 0.0005 to 0.05%, relative to the polycondensate solution, for good stabilization of the hue. For example, the iodine color number (DIN 53995) is suitable for determining the hue.
Preferably, the pH is adjusted again to a pH of from 2.0 to 3.0, preferably from 2.4 to 2.9, with sulfuric acid and/or formic acid after a maturing time of from 4 to 48 hours after the first formulation, with the result that a further improvement in the shelf-life can be achieved. Particularly with the use of formic acid, this maturing time can be shortened to, preferably, from 4 to 18 hours, so that storage capacity can be saved and the product can be delivered earlier without there being any danger of swelling and premature crosslinking. Suitable amounts of acid for this pH adjustment are from 0.001 to 0.2 mol of sulfuric acid and/or formic acid per kg of solid resin (calculated as proton content).
The products prepared by the process according to the invention have an average molecular weight (Mw) of at least 1 000, preferably from 2 000 to 1 000 000 g/mol.
The polycondensate solution is free of inorganic salts since no inorganic bases are used for reducing the organic chlorine content.
By means of the process according to the invention, the epichlorohydrin used is optimally utilized for the addition reaction with the polyamidoamine with only a low level of secondary reactions, so that undesired secondary components, such as DCP and CPD, are formed only in minor amounts and, in spite of the use of relatively little epichlorohydrin, high wet strength activity is achieved.
The polycondensate solutions prepared according to the invention are used as paper assistants, especially for treating paper, board and cardboard to impart wet strength. The treatment is effected in a manner known per se by adding the aqueous solution of the polycondensate to a suspension of the fiber raw material, which, in addition to cellulose or groundwood, may contain, for example, fillers, further paper assistants, such as retention aids, sizes, fixing compositions, chlorine-free wet strength agents, such as polyisocyanates, dyes, optical brighteners, etc. Paper is formed therefrom by drainage, either in the laboratory on a sheet former, for example Rapid-Kxc3x6then, or on the industrial scale on a paper machine. The amounts used depend on the desired wet strength effect. As a rule, it is suitable to use amounts of from 0.01 to 2.5% by weight, preferably from 0.1 to 1.5% by weight, of solid resin, relative to dry fiber.
Preferably a combination of the polycondensates prepared according to the invention and chlorine-free hydrophilized polyisocyanates, as described, for example, in the German Offenlegungsschriften (German Published Specifications) DE-A 4 211 480, DE-A 4 226 110, DE-A 4 436 058, DE-A 4 446 334, DE-A 1 951 6405 and German Patent Application No. 1 952 0092.6, since, with this combination, particularly good effects are achieved in the case of the filler retention and wet strength of paper through a synergy of the two components and, particularly advantageously, charge control of the material system of the paper machine can be carried out, which is advantageous particularly in the production of decorative and laminated paper.
In addition, owing to their high cationic charge, the polycondensate solutions prepared according to the invention promote the drainage of the stock mixture on the paper machine and the retention of fillers, dyes, optical brighteners and other paper assistants, for example reactive and polymer sizes, resulting in many cases in higher efficiency of these assistants, such as increased depth of color or improved sizing effect.
Furthermore, the polycondensate solutions prepared according to the invention are suitable for converting any desired fillers and pigments into cation form, such as, for example, kaolin, clay, bentonite, calcium carbonate, talc or titanium dioxide, which are used in the paper industry but may also advantageously be used in other applications. It is preferable to convert into cationic form titanium dioxide, which is used as a white pigment in the production of decorative paper, where a high cationic charge in combination with a fine distribution of the white pigment is required in order to obtain high opacity. The polycondensate solutions prepared according to the invention are also suitable for converting into cationic form natural products, such as potato, maize or wheat starch, which can, for example, be enzymatically or oxidatively degraded, with the result that, for example, the intrinsic retention during use in the paper pulp can be improved, or for converting into cationic form cellulose powder which, after conversion to cationic form, can be used, for example, for improving the retention.
The use of the polycondensate solutions prepared according to the invention in the paper surface, for example together with starch, sizes, polyisocyanates and/or pigments, dyes and optical brighteners and further additives, in the size press or film press and also as crosslinking agents in the paper coat is also possible.
Owing to their rapid crosslinking during the drying of the paper web in the drying section of the paper machine, they result in good wet strength from the paper machine itself, which can be further increased by storage at room temperature or by treatment at elevated temperatures. The polycondensates prepared according to the invention do not influence the absorptivity of the paper, so that they can advantageously be used in the production of tissue and hygiene papers. Use in the production of decorative and laminated papers, where they result in good retention of titanium dioxide and other fillers in addition to a high wet strength effect and contribute toward high opacity, is also preferred. An advantage of the polycondensates prepared according to the invention is their easy reheatability during the processing of waste and recycled paper. For example, sodium hydroxide solution and/or peroxodisulfate are particularly suitable for the digestion.
The polycondensates can furthermore also be used as textile assistants for the treatment of natural and synthetic fiber materials. An important application form is textile printing, in which a print paste is prepared, for example, from a basic polyamidoamine, a polycondensate prepared according to the invention and optionally homo- or copolymers of vinyl compounds and further additives, the textile fiber is printed with this print paste on a printing unit and then condensation is effected at elevated temperature.


Compositions to prevent or reduce hair loss, allowing the body to maintain normal, healthy hair growth, comprising a penetration enhancer together with a testosterone blocker or a vascular enhancer, or both.

My invention relates to preparations useful for maintaining normal, healthy hair bulb function, for preventing hair loss, and for medically treating androgenic alopecia and like dermatological diseases. I will first review pertinent hair biology, then discuss prior art teachings in the field, and then describe my invention.
Hair bulbs are responsible for normal, healthy hair growth and retention. Hair bulbs are located in the skin, about {fraction (3/16)} of an inch below the skin surface. They are located just above the fatty layer at the very lower most position of the skin.
The majority of facial and body hair growth is stimulated by androgens. However, the growth of scalp hair has been shown, in genetically programmed individuals, to be inhibited by 5xcex1-dihydrotestosterone (xe2x80x9cDHTxe2x80x9d) in individuals who exhibit a hereditary pre-disposition to baldness. Ebling, Dermatol. Clin. S. 467 (1987); Lucky, 4 Biochem. Soc. Transc. 597 (1988); Brodland et al., 47 Cutis 173 (1991). DHT is produced by reducing testosterone with a 5xcex1-reductase enzyme. The phenotypic expression of baldness does not occur in the absence of testosterone. Androgenic alopecia or common baldness represents 99 percent of all cases of hair loss. Broadland, id.
The mechanism through which androgens regulate the biology of hair is by modulating the hair growth cycle. Ebling, 4 Biochem. Soc. Trans. 597; Bergfield et al., 5 Dermatol. Clin. 491. The effect of DHT on hair growth appears to be related to local rather than systemic levels of the hormone. This is because the capacity of scalp skin from balding individuals to convert testosterone (xe2x80x9cTxe2x80x9d) to DHT is greater than that observed in the scalp of non-balding individuals. Lucky, supra; Schweikert et al., 38 J. Clin. Endocrinol. Metab. 811.
To prevent hair loss, maintain the health of hair bulbs, or to treat baldness, several compositions are known in the art. We discuss them now.
Hair loss prevention preparations are known in the art. These include natural product preparations, biological products, vascular toners and testosterone blockers. Several prior art compositions are discussed in the accompanying Petition To Make Special and its accompanying references, the contents of which are incorporated herein by reference.
Natural Products. Several inventors disclose natural compositions. Casero, U.S. Pat. No. 5,340,579, discloses a composition comprising (a) mucopolysaccharides, (b) human umbilical cord extract, (c) tetrahydrofurfuryl nicotinate, and (d) pharmaceutically and cosmetically acceptable excipients. Buck, U.S. Pat. No. 5,512,275 and 5,609,858, discloses a formulation for the treatment of androgenic alopecia, comprising liquor carbonis detergens in combination with spirits of camphor, castor oil, isopropyl alcohol. Chizick et al., U.S. Pat. No. 5,972,345, discloses a combination of saw palmetto extract, African pygeum extract, and stinging nettle extract.
Biological Products. Hoke, U.S. Pat. No. 5,994,319, discloses using genetic material as a anti alopecia therapeutic. Hoke proposes using anti-sense oligonucleotides targeting 5-xcex1 reductases in conjunction with other hair growth enhancers. Tien, U.S. Pat. No. 5,574,011, discloses the use of a class of LHRH analogs for treating male pattern baldness. Messenger, U.S. Pat. No. 6,020,327, discloses administering aromatase inhibitors to treat hair loss. Liao et al., U.S. Pat. Nos. 5,422,371 and 5,605,929, discloses a class of anti-androgenic compounds.
Vascular Toners. Several organic chemicals are known to affect the hair growth and hair retention cycle. These include minoxidil. I refer to minoxidil and similar kinds of compounds as xe2x80x9cvascular toners,xe2x80x9d because they are believed to be effective due to their impact on local blood circulation.
Minoxidil has been shown to stimulate hair growth or inhibit the loss of hair in a number of patients beginning to develop androgenic alopecia. Minoxidil is the generic name for 6-(1-piperidinyl)-2, 4-pyrimidinediamaine 3-oxide. Its preparation is disclosed in Anthony, W. C. et al., U.S. Pat. No. 3,382,247 (1968); McCall, J. M., et al., 40 J. Organic Chem. 3304 (1975); Gorecki, D. K. J., 17 Analytical Profiles of Drug Substances 185 (Academic Press, New York 1988). It is more soluble (by weight minoxidil/volume of solvent) in non-polar solvents than polar ones (75 mg/ml in propylene glycol; 44 mg/ml in methanol; 6.5 in dimethyl sulfoxide; 2.2 mg/ml water).
Minoxidil is medically classified as an anti-hypertensive. It affects heart rate and rhythm. It has thus been used in an oral formulation as a cardiac drug. Andersson, O., 205 Acta Med. Scand. 213 (1979); Moser, M., 26 Advan. Cardiol. 38 (1979). over dosage may create cardiac arrhythmias or other adverse side effects. See e.g., Carlson, E. S., 39 Toxicol. Applied Pharmacol. 1 (1977).
Minoxidil is also medically classified as an anti-alopecia agent. Its efficacy in treating early male pattern baldness has been described in numerous published articles. E.g., Olsen, E. A. et al., 13 J. Am. Acad. Dermatol. 185 (1985); Novak, E., 24 Int. J. Dermatol. 82 (1982). Its limited percutaneous absorption and secretion is described in Franz, J. T., 121 Arch. Dermatol. 203 (1985).
The mechanism by which minoxidil alters the hair growth cycle is uncertain. It is thought to act by increasing vascular circulation to the hair follicle. It is known that minoxidil effectiveness is more pronounced in scalp areas which are more vascular.
Topical minoxidil is know to have certain shortcomings. It is effective in only about eight percent of adult male users. It produces xe2x80x9clanugo,xe2x80x9d or baby-type, hair which is relatively thin. Further, and perhaps most significantly, after approximately 30 months of continuous use, minoxidil shows a sharp drop in effectiveness. After about thirty months of use, about half of the new hair growth falls out. Thus, while the user has somewhat more hair than originally, the user has less hair than originally seen.
Testosterone Inhibitors. Inhibitors of steroid metabolism, particularly those that inhibit the conversion of testosterone to dihydro testosterone, have shown effects on hair cycles, including inhibition of hair loss. One class of enzymes targeted by these inhibitors are the steroid 5-xcex1 reductases.
Certain 5xcex1-reductase inhibitors have been shown to inhibit hair loss. For example, stump-tail macaque monkeys treated with the 5xcex1-reductase inhibitor 17b-N,N,- dimethylcarbamoyl- 4-methyl- 4-aza-5xcex1-androstan- 3-one undergo significantly less age related hair loss than untreated monkeys. Rittmaster et al., 65 J. Clin. Endocrinol. Metab. 188 (1987). Similarly, finasteride, a 5xcex1-reductase inhibitor, miniaturizes scalp hair follicles, reversing the balding process. xe2x80x9cMerck""s Propecia Shows Promise In Hair Loss,xe2x80x9d Marketletter (Mar. 31, 1997). These inhibitors are thought to work by inhibiting the reduction of testosterone to DHT, as DHT is considered to be the more active form. The use of a combination of finasteride and minoxidil demonstrated that, in combination, these two drugs increased the rate of hair growth when compared to either compound administered alone. Diani, 74 J. Clin. Endocrinol. Metabol. 345.
Minoxidil used in conjunction with effectors of steroid metabolism, leads to enhanced hair growth and decreased rates of hair loss.
Testosterone blockers are known in the art (I use the term xe2x80x9ctestosterone blockerxe2x80x9d to denote a competitive antiandrogen which inhibits the binding of testosterone or DHT onto its cell surface binding site, rather than a compound which is used to inhibit the reduction of testosterone into DHT.). Also known is their use systemically (orally or intravenously). As systemic therapeutics, they are known in the art as having a key shortfall: their long term efficacy is compromised by their blocking of the androgenic feedback inhibition of gonadotropin secretion. This interference results in elevated gonadotropin secretion, which in turn increases testicular secretion of testosterone. The higher level of testosterone eventually overcomes the action of the antiandrogen. Liao, supra, at col. 3, lines 16-31.
Thus, what is needed in the art is a safe and effective way to maintain both the healthy function of hair bulbs, and the health of existing hair, that avoids the shortfalls seen in the prior art.
I have invented a kind of hair loss prevention composition. My invention is a new combination of already known types of compounds. My invention can be used either cosmetically (to maintain healthy hair growth) or pharmaceutically (to treat a medical condition). It can be made using components already known in the art, allowing one to enjoy the predictability of use available with these old compounds. My invention is flexible enough, however, to also allow one to substitute newly-discovered compounds substantially equivalent to the already known compounds. Thus, my invention can be adapted to allow the user to use the safest, most effective components then available.
I have found that certain compounds have greatly improved effectiveness - achieving ten times the benefit, or an entire order of magnitude - if combined with a skin penetration enhancer. The penetration enhancer delivers these compounds to the hair bulb, where the compounds are most needed.
I have thus found that testosterone blockers, if applied topically (rather than systemically administered), are effective in preventing hair loss, and if used in conjunction with a dermal penetration enhancer. Such topical use avoids precipitating the systemic increase in testosterone production seen with oral administration, by minimizing systemic interference with normal gonadotropin secretion. I have also found that vascular toners, if applied topically in conjunction with a dermal penetration enhancer, work much better.
My invention includes a skin penetration enhancer used together with a testosterone blocker or a vascular enhancer, or both. I first discuss each component individually, and then discuss the combinations of these components that I have found most acceptable.
You can use a variety of skin penetration enhancers to make compositions that work as I intend. Penetration enhancers and skin penetrating formulations are known in the art. These include the variety of formulations used from time to time for both psoriasis treatment pharmaceuticals, and psoriasis prevention nutritional supplements and cosmetics.
The penetration enhancer (or penetration agent) should be accepted for human use by relevant government agencies. Thus, dimethyl sulfoxide, while within the scope of the claims, is not a preferred penetration enhancer where that compound is not approved for human topical use. The penetration enhancer should not chemically react with any other ingredient to impair or alter the composition""s stability and shelf life. Thus, one should examine the possible reactivity of a given penetration enhancer with a given testosterone blocker or vascular toner.
The penetration agent should be cosmetically acceptable. Thus, while I have tested dimethyl acetate, I do not favor it. While it is within the scope of the claims, it is a weak penetration enhancer. Thus, one needs to use a lot of it. In these high amounts, it smells bad. In contrast, methyl acetate is odorless, and I have tested and found it acceptable.
Several inventors disclose liposome technology to deliver cosmetic and dermatology materials. See, for example, Lishko et al., U.S. Pat. No. 5,753,263, discloses using liposomes to selectively deliver a composition to hair follicles. Liposomes are made of fatty material, and are suitable for delivering homogenous types of materials. As such, it may be difficult for a liposome to in fact work with a combination of a polar compound (like a minoxidil vascular toner) and a non-polar compound (such as a progesterone testosterone blocker). I thus do not consider liposome technology within the scope of the term xe2x80x9cpenetration enhancerxe2x80x9d in this patent.
My invention works with a variety of vascular toners. One can make compositions within the scope of my invention with minoxidil analogs or derivatives, or with other anti-alopecia agents, such as diphencyprone, which work in a similar way, by improving local blood flow to the affected hair bulbs. Because it has such a broad volume of use and scientific study, I prefer to use minoxidil. I thus use it as an example throughout this specification.
A vascular toner, if used to maintain healthy function of hair bulbs, must be delivered to the small blood vessels feeding the hair bulbs. I have thus found that the effectiveness of the vascular toner is greatly improved if it is topically applied along with a penetration enhancer. This allows the vascular toner to act locally.
The vascular toner must be carefully titrated against the penetration enhancer. For example, for a given concentration of minoxidil, one needs to use the penetration enhancer in the appropriate concentration. If a given penetration enhancer is used in a too high concentration, the minoxidil may penetrate through the skin and reach the systemic blood circulation. It can there, if present in sufficient amount, cause side effects as seen by taking oral minoxidil. Thus, it is necessary to adjust the amounts of penetration enhancer and vascular toner, depending on the concentration and specific identity of the enhancer and the toner.
Adding a penetration enhancer to the vascular toner appears to fundamentally change the biological mechanism by which the vascular toner works. This is shown by the qualitatively different results seen between minoxidil and my compounds. The two products produce different types of hair, and for different time periods.
Minoxidil without a penetration enhancer (as available in ROGAINE(trademark) topical minoxidil U.S.P.) produces a different kind of hair than does minoxidil used with a penetration enhancer. It is known in the art that topical minoxidil without a penetration enhancer (as is commercially available in ROGAINE ((trademark)) topical minoxidil U.S.P., commercially available from Pharmacia and Upjohn Inc., Bridgewater, N.J.) results in thin, baby-like, temporary hair, called xe2x80x9clanugoxe2x80x9d hair. I have found that my compounds, by contrast, result in good, coarse, xe2x80x9cterminalxe2x80x9d hair, hair which is normal, permanent adult hair.
This indicates that minoxidil without and with penetration enhancer may act on different types of hair bulbs, or produce different responses from the same hair bulbs. Minoxidil without enhancer is only weakly soluble in polar solvents. See supra. It thus has difficulty diffusing to the deeply located hair bulbs (roots) which are located just above the deep fat layer. Minoxidil without enhancer may thus affect only hair bulbs located close to the skin surface, or located in a less fatty skin layer, or hair bulbs most sensitive to changes in blood flow. Alternatively, it may affect the same hair bulbs, but with such weak or attenuated effect that the hair bulbs produce a different type of hair.
In contrast, my compounds produce normal, terminal hair. This indicates that my compounds act directly on the mature, adult hair bulbs responsible for terminal hair growth.
Further, it is known in the art that minoxidil users experience a sudden drop in hair thickness after about thirty months of usage. I thus have sought the time at which my compounds have a sudden drop in effectiveness. Surprisingly, I have found that my compounds apparently do not lose effectiveness at all, even after using them for substantially greater than thirty months. This confirms that while my compounds appear to simply restore or preserve normal hair bulb function, the prior art compositions do not restore normal hair bulb function, but actually provoke an abnormal functionxe2x80x94the growth by an adult of baby like, temporary hair. That this function is abnormal is confirmed by its drop in effectiveness after thirty months; such a drop in efficacy indicates a xe2x80x9ctolerancexe2x80x9d acquired against the intervention, rather than the maintenance of a permanent, healthy state.
This indicates that the physiological mechanisms and biomedical pathways of the two preparations are different. Minoxidil alone, in the concentrations typically used, may actually temporarily alter a normal adult body function (causing the adult body to temporarily produce infant hair). In contrast, my invention simply maintains the normal function of the healthy adult body hair bulb, allowing it to continue to produce normal adult hair as long as the compound is used.
I have also found that the effect of the formulations depends on location of administration. Using the specific formulations disclosed here, I have observed decreases in hair loss, and a consequent statistically significant increase in the amount of healthy mature hair, after 4.0-4.5 months on the frontal scalp. On the crown and back of the head, by contrast, I have observed statistically significant results after 4.5-5.0 months. The frontal scalp may react faster because it enjoys greater vascularization and blood flow than the other parts of the scalp.
My invention works with a variety of testosterone blockers. I prefer to use a blocker already approved for human use by the United States Food and Drug Administration, as these types of testosterone blockers, if used in pharmaceutical (as opposed to cosmetic) versions of my invention, do not need to undergo as lengthy and expensive a process to verify their safety and efficacy as used in pharmaceutical products. Examples include flutamide, cyproterone acetate, spironolactone, progesterone, or analogs or derivatives of any of these (e.g., 17-hydroxy-16-methylene-xcex946-progesterone, 17xcex1-hydroxyprogesterone).
I have found several surprising things about testosterone blockers. First, they are not actually necessary for my invention to work; minoxidil alone is effective on 8% of patients, while the same amount of minoxidil administered with the proper amount of a penetration enhancer is effective on 35% of patients. Second, testosterone blockers added to such a mix are synergistically beneficial, increasing the efficacy from 35% to 85% of patients.
One testosterone blockler is the anti alopecia compound cioteronel. Cioteronel is the common name for hexahydro-4-(5-methoxyheptyl)-2(1H)-pentalenone. It is also known, or is commercially available, as X-ANDRON(trademark), CPC-10997, CYOCTOLT(trademark), and EXANDRON(trademark). It is a clear, colorless oil, soluble in lipid and relatively non-polar solvents. Its preparation is disclosed in Kasha, W. J., PCT Int""l Patent Application 83/04,019 (1983), 101 Chem. Abstr. 23037k (1984). Its use is disclosed in U.S. Pat. No. 4,689,345. Its inhibition of DHT binding in vitro is disclosed in Rec. Adv. Chemotherapy (Proc. 14th Int""l Congr. Chemotherapy Antimicrob., Sect. 1) at 261-70 and 273-74 (Univ. Tokyo Press, 1985). Its cutaneous metabolism and clinical pharmacokinetics is disclosed in de Zeeuw et al., 7 Pharm. Res. 638 (1990), Weichers et al., 65 Int. J. Pharm. 77 (1990).
Another testosterone blocker is progesterone, pregn-4-ene-3, 20-dione (commercially available as CORLUTINA(trademark), CORLUVITE(trademark), CYCLOGETS(trademark), GESTIRON(trademark), GESTONE(trademark), LIPOLUTIN(trademark), LUTOCYCLIN(trademark), PROGESTIN(trademark), CP progesterone powder, etc . . . ). Progesterone is insoluble in water and soluble in alcohol, acetone, dioxane, and concentrated sulfuric acid. It is sparingly soluble in vegetable oils. Its isolation, structure and biological activity is described at length in Bardin et al. (eds.), Progesterone and Progestins (Raven Press, New York 1982). I prefer to use progesterone as the sole testosterone blocker.
The penetration enhancer and the vascular toner or testosterone blocker, or both, may be mixed with a carrier vehicle. You can use a variety of vehicles to make my invention. The vehicle is simply a cosmetically safe, medically safe solvent for the active ingredients. The vehicle should not adversely and significantly chemically react with the active ingredients.
For example, propylene glycol, water and isopropyl alcohol may be used as vehicles. These may be used alone or in combination.
The vehicle can optionally provide functions in addition to simply dissolving the active ingredients. For example, one can use a moisturizing vehicle, or a vehicle containing sunscreen. For a moisturizing or moisture retaining vehicle, one can use a vehicle made from a combination of (ranked in order of quantity used) water, mineral oil, petrolatum, lanolin, sorbitol solution, stearic acid, lanolin alcohol, cetyl alcohol, glyceryl stearate/PEG-100 stearate, triethanolamine, dimethicone, propylene glycol, tri(PPG-3 myristyl ether) citrate, disodium EDTA, methylparaben, ethylparaben, propylparaben, fragrance, xanthan gum, butylparaben, and methyldibromo glutaronitrile.
It may be desirable to use a vehicle containing one or more sunscreens. This is because my preparations are used on the tops of balding scalps. Balding scalps are often largely unprotected from sun damage, as the user may not wear headgear and the balding scalp lacks the sun shielding dense hair layer present on a healthy scalp. Adding sunscreen thus can protect the scalp from possible sun damage. Sunscreens, and vehicles containing sunscreen compounds, are widely known in the art. See, e.g., U.S. Pat. No. 4,522,807.
Other cosmetic vehicles are widely known in the art. I prefer to use VEHICLE/NT(trademark) as the vehicle. I prefer to use VEHICLE/N((trademark)) because it has a cosmetically attractive xe2x80x9cfeelxe2x80x9d to the user. Vehicle/N((trademark)) is commercially available from the Neutrogena Dermatologics division of Johnson and Johnson, Inc., New Brunswick, N.J. It is currently available in two formulations, regular and mild. They are both versatile liquid vehicles for extemporaneous compounding of topical drugs. Both formulations solublize selected dermatological agents and provide astringent and drying actions.
The VEHICLE/N((trademark)) ingredients are SD alcohol 40 (45%), purified water ( less than 45%), laureth-4 ( greater than 4%), isopropyl alcohol (4%) and propylene glycol ( less than 4%). The VEHICLE/N((trademark)) mild ingredients are purified water ( greater than 37.5%), SD alcohol-40 (37.5%), isopropyl alcohol (5%) and laureth-4 ( less than 5%). To compound with VEHICLE/N, add the appropriate quantity of active ingredient to yield the intended concentration.
VEHICLE/N((trademark)) is available as 50 mL of vehicle in a plastic bottle with applicator top. The bottle is filled only to xc2xe capacity, to ensure proper mixing. For 50 mL of VEHICLE/N, use the following amounts:
For fastest dissolution, when tablets are used, crush them to a powder and then add the powder to the vehicle. When capsules are used, add the capsule contents only to the vehicle, and discard the capsule shell. Shake the mixture gently. Most capsule contents and bulk active ingredients will dissolve within minutes, though some may take longer.
VEHICLE/N(trademark) is available in a bottle with an APPLIDERM((trademark)) applicator top. The APPLIDERM((trademark)) applicator unit automatically filters the compounded mixture and provides a convenient, spill-proof, self-contained unit for topical application. To use the APPLIDERM((trademark)) applicator unit, push the applicator firmly into the bottle using the white cap as a holder. Screw the cap all the way down to seat the applicator. Shake well. If tablets are dissolved in the vehicle, then the user should be instructed to allow the solution to stand overnight and to shake vigorously before the first use. VEHICLE/N((trademark)) should not be used near fire or open flame due to alcohol content. Both VEHICLE/N((trademark)) and VEHICLE/N((trademark)) mild contain substantial alcohol and are not suitable for use in acute dermatoses. Stinging may be noted if used on irritated or abraded skin. Avoid contact with eyes or eyelids. If the product accidentally comes in contact with eyes, rinse thoroughly with water and contact physician. Keep out of reach of children. VEHICLE/N((trademark)) and VEHICLE/N((trademark)) mild are contraindicated in persons who have shown hypersensitivity to any of the listed ingredients.
Given a constant amount of testosterone blocker or vascular toner, I have found that lower concentrations of penetration enhancer can decrease the efficacy of the final formulation, while higher concentrations of penetration enhancer increase the risk of adverse side effects due to systemic penetration of the other active ingredient(s).
Similarly, you may use different testosterone blockers for the same effect, and may use more or less of it. Using more testosterone blocker allows one to use relatively less penetration enhancer, or a weaker enhancer. Titration of the two components against one another is a conventional technique well known in the art of pharmaceutical and cosmetics formulation. Such techniques are already used to titrate formulations for the wide variety of trans-dermal drugs and cosmetics currently available.
For example, in a four ounce quantity of liquid containing 5 drops of trimethyl acetate, I prefer to use one percent (by volume) of soluble progesterone (U.S.P.).
A preferred formulation is:
The following preparation is acceptable, and within the scope of the claims, but I do not prefer it:
Alternatively, an ethyl alcoholxe2x80x94waterxe2x80x94propylene glycol solution may be used as the diluents and vehicle. For 100 mL of this formulation, use:
These are my preferred formulations. These may be varied as desired, but it is necessary to watch for unwanted side effects possibly due to unwanted systemic penetration of the active ingredient(s). For example, minoxidil is pharmaceutically and cosmetically effective topically at anywhere from about 0.01 grams to about 50 grams per four ounces, depending on the frequency of topical administration. Testosterone blockers are also pharmaceutically and cosmetically effective topically at anywhere from about 0.01 grams to about 50 grams per four ounces, depending on the frequency of topical administration. With the higher concentrations, however, increasing the amount of penetration enhancer creates a greater risk of adverse side effects.
I have discussed several different specific formulas. I have found these most useful. One can, however, vary the constituents to achieve the same effect without having a substantially different product. For example, one can use a different testosterone blocker, or a weaker penetration enhancer in a higher concentration.


A process is provided for producing fast curing bonded with phenolic resin, which comprises pulverulent phenolic resins mixed with or applied to the substrate to be adhered together with pulverulent addition polymers selected from the group consisting of polyvinyl alcohols and addition polymers, stabilized by hydroxyl-containing protective colloids of at least one monomer selected from the group consisting of the vinyl esters of branched or unbranched carboxylic acids of 1 to 12 carbon atoms, the esters of acrylic acid and methacrylic acid with branched or unbranched alcohols of 1 to 12 carbon atoms, vinylaromatics, vinyl halides, olefins and dienes, and subsequently, by the employment of elevated temperature and optionally elevated pressure, cured and processed into a shaped article.

1) Field of the Invention
This invention is directed to a process for producing fast curing bonded with phenolic resin by employing, molding compounds together with pulverulent phenolic resins, pulverulent addition polymers selected from the group consisting of polyvinyl alcohols and addition polymers stabilized by hydroxyl-containing protective colloids.
2) Background Art
The importance of thermosetting phenol-formaldehyde resins, for example, hexa novolaks or resoles, as binders for a very wide variety of applications has greatly increased in recent years. Typical applications are, for example, binders in filter papers, foundry sand, ceramics, fiber mats and wood fiber boards. The use of phenol-formaldehyde resins as a thermosetting binder in most cases requires a thermally initiated, intensive crosslinking of the polymer chains to form a three-dimensional, molecular network.
In the interests of industrial use, where fast cycle times are important, development work has concentrated in particular on accelerating the crosslinking reaction, the curing, of these polymer systems.
Many prior artisans were concerned with catalyst systems which accelerate the condensation of phenol functions with aldehyde functions and were particularly interested in achieving a chemical reaction in the ortho position of the phenol ring. Examples thereof are known from WO-A 93/08223, which describes solvent-free, solid hotmelt adhesive systems with divalent metal salts as catalysts. The disadvantage here is the excess of up to 1.7 mol% of free formaldehyde which can lead to environmental problems.
U.S. Pat. No. 4,112,188 describes a process for accelerating the cure of resoles by means of boron compounds. But this process utilizes not solid, but liquid systems in aqueous solution.
The curing reaction of binder mixtures based on phenolic resin can also be accelerated by ester compounds. For example, DE-A4331656 (Derwent Abstract AN 94-286789), discloses that triacetin is useful as a cure accelerator. However, this system works only in aqueous solution and in the presence of lignin. Similarly, the Australian patent specification AU-B-22974/88 describes ester compounds, especially lactones, organic carbonates and carboxylic esters as useful cure accelerators for the liquid phenolic resins known as resoles.
Polymeric cure accelerators are likewise known. U.S. Pat. No. 5,223,587 claims a binder for wood fibers which is comprised of a powdery mix of highly condensed phenolic resins, incompletely cured phenolic resins (hexanovolaks) and optionally, coconut shell powder. U.S. Pat. No. 4,426,484 discloses accelerating the curing of solid resoles by adding solid novolak resins comprising resorcinol. The disadvantage with either process is the increased emission of formaldehyde and phenol from the starting materials used. In contrast, the use of powdered green tea, as known from U.S. Pat. No. 4,109,057, offers an environmentally benign alternative to accelerating the cure of phenolic resins by means of polymeric compounds. However, the high cost is a decisive bar to industrial use.
It is an object of the present invention to provide a process whereby the curing of solid phenolic resins, especially hexanovolaks, is accelerated.
It has now been found, surprisingly, that polyvinyl alcohols and addition polymers stabilized by hydroxyl-containing protective colloids accelerate the curing of phenolic resins.
The invention accordingly provides a process for producing fast curing bonded with phenolic resin, molding compounds which comprises pulverulent phenolic resins being mixed with or applied to the substrate to be adhered together with pulverulent addition polymers selected from the group consisting of polyvinyl alcohols and addition polymers, stabilized by hydroxyl-containing protective colloids, of one or more monomers from the group of the vinyl esters of branched or unbranched carboxylic acids of 1 to 12 carbon atoms, the esters of acrylic acid and methacrylic acid with branched or unbranched alcohols of 1 to 12 carbon atoms, vinylaromatics, vinyl halides, olefins and dienes, and subsequently, by the employment of elevated temperature and optionally elevated pressure, cured and processed into a shaped article.
Suitable polyvinyl alcohols are partially or fully hydrolyzed polyvinyl alcohols, preferably having a degree of hydrolysis of 85 to 100 mol% and a Hxc3x6ppler viscosity of 1 to 60 mPas, measured in 4% strength aqueous solution (method of Hxc3x6ppler at 20xc2x0 C., DIN 53015). It is also possible to use vinyl alcohol copolymers which, in addition to the vinyl alcohol and vinyl acetate units, contain other monomer units, for example 1-methylvinyl acetate or 1-methylvinyl alcohol units, preferably in an amount of 0.5 to 10% by weight, based on the total weight of the copolymer. The vinyl alcohol homo- and copolymers mentioned are commercially available or obtainable in a manner known to one skilled in the art, by hydrolysis or alcoholysis of the corresponding vinyl acetate homo- and copolymers.
Vinyl esters preferred for the protective colloid-stabilized addition polymers are vinyl acetate, vinyl propionate, vinyl butyrate, vinyl 2-ethylhexanoate, vinyl laurate, 1-methylvinyl acetate, vinyl pivalate and vinyl esters of alpha-branched monocarboxylic acids of 9 to 11 carbon atoms, for example VeoVa9(copyright) or VeoVa10(copyright) (trade names of Shell). Vinyl acetate is particularly preferred.
Methacrylic esters or acrylic esters preferred for the protective colloid-stabilized addition polymers are methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, propyl acrylate, propyl methacrylate, n-butyl acrylate, n-butyl methacrylate, 2-ethylhexyl acrylate. Particular preference is given to methyl acrylate, methyl methacrylate, n-butyl acrylate and 2-ethylhexyl acrylate.
Preferred vinylaromatics are styrene, methylstryene and vinyltoluene. The preferred vinyl halide is vinyl chloride. The preferred olefins are ethylene and propylene and preferred dienes are 1,3-butadiene and isoprene. Optionally, 0.05 to 10.0% by weight, based on the total weight of the monomers, or comonomers can be present in addition, for example acrylic acid, acrylamide, vinylsulfonic acid, 2-acrylamidopropanesulfonate, vinyltriethoxysilane, gamma-methacryloyloxypropyltriethoxysilane, N-methylolacrylamide (NMA).
Preferred protective colloid-stabilized addition polymers are vinyl ester polymers, (meth)acrylic ester polymers, vinyl chloride polymers and styrene polymers.
The hereinbelow recited polymers are particularly preferred, the weight percentages, if necessary, including the comonomer fraction, adding up to 100% by weight:
from the group of the vinyl ester polymers: vinyl acetate polymers, vinyl acetate-ethylene copolymers having an ethylene content of 1 to 60% by weight; vinyl acetate-ethylene vinyl chloride copolymers having an ethylene content of 1 to 40% by weight and a vinyl chloride content of 20 to 90% by weight; vinyl acetate copolymers with 1 to 50% by weight of one or more co-polymerizable vinyl esters such as vinyl laurate, vinyl pivalate, vinyl esters of an alpha-branched carboxylic acid, especially vinyl versatates (VeoVa9(copyright), VeoVa10(copyright), VeoVa11(copyright)), which optionally contain 1 to 40% by weight of ethylene in addition; vinyl acetate-acrylic ester copolymers containing 1 to 60% by weight of acrylic ester, especially n-butyl acrylate or 2-ethylhexyl acrylate, which optionally contain 1 to 40% by weight of ethylene in addition;
from the group of the (meth)acrylic ester polymers: polymers of n-butyl acrylate or 2-ethylhexyl acrylate;
copolymers of methyl methacrylate with n-butyl acrylate and/or 2-ethylhexyl acrylate;
from the group of the vinyl chloride polymers (in addition to the abovementioned vinyl ester/vinyl chloride/ethylene copolymers): vinyl chloride-ethylene copolymers and vinyl chloride/acrylate copolymers;
from the group of the styrene polymers: styrene-butadiene copolymers and styrene-acrylic ester copolymers such as styrene-n-butyl acrylate or styrene-2-ethylhexyl acrylate having a styrene content of 10 to 70% by weight in each case.
The polymers are produced in a known manner by an emulsion polymerization process and subsequent drying, for example, spray drying, of the aqueous polymer dispersions obtainable thereby.
The proportion of hydroxyl-containing protective colloid can be added before or during the polymerization, or else after the polymerization; that is, before, during or after the drying step. Particular preference is given to the process described in EP-B 687317 for preparing water-redispersible, protective colloid-stabilized addition polymers, whose disclosure in this respect is incorporated herein by reference. The last procedure mentioned provides the particularly preferred, water-redispersible addition polymers, redispersible meaning that the agglomerates obtained on drying will on addition to water, disintegrate back to the primary particles, which are then dispersed in the water.
The hydroxyl-containing protective colloids generally used for stabilizing the addition polymers are polyhydroxy compounds such as fully or partially hydrolyzed polyvinyl alcohols, water-soluble polysaccharides such as starches (amylose), hydroxyalkyl ether starches, dextrins, cyclodextrins, dextran, xylan and celluloses and also derivatives thereof such as carboxymethyl-, methyl-, hydroxyethyl- and hydroxypropyl-celluloses. By water-soluble is understood in this context that the solubility in water is more than 10 g per liter under standard conditions. Preference is given to one or more partially hydrolyzed polyvinyl alcohols having a degree of hydrolysis of 75 to 99 mol % and a Hbppler viscosity (4% strength in aqueous solution, DIN 53015, method of Hbppler at 20xc2x0 C.) of 1 to 60 mPas, especially 4 to 35 mpas. The protective colloid fraction is 1 to 30% by weight based on the polymer fraction to be stabilized. Particular preference is given to 8 to 30% by weight.
Solid phenolic resins which can be modified with the pulverulent addition polymer (polymer powder) are also referred to as novolaks and are obtainable by reaction of aldehyde with phenol in-a phenol/aldehyde ratio of greater than 1, usually under acidic conditions. Examples of phenols are, besides phenol itself, its alkyl-substituted derivatives such as the cresols and xylenols, halogen-substituted phenols such as chlorophenol, polyhydric phenols such as resorcinol or pyrocatechol, and also polycyclic phenols such as naphthol and bisphenol A. Examples of useful aldehydes include formaldehyde, paraformaldehyde, acetaldehyde and butyraldehyde. Preference is given to phenol-formaldehyde resins.
Novolaks are mixtures of differently advanced resin complexes composed of methylene-linked polyphenols. Owing to the absence of reactive groups, novolaks are not self-curing, but require a curing agent. Examples of curing agents are paraformaldehyde or hexamethylenetetramine. In general, novolak compositions include 1 to 15% by weight of a curing agent, based on the novolak fraction. Curing by heating causes the chainlike novolak molecules to become crosslinked. To accelerate this crosslinking, the invention utilizes 0.1 to 40% by weight preferably 3 to 40% by weight, more preferably, 10 to 30% by weight, in each case based on the fraction of phenolic resin and polymer powder.
The phenolic resins modified with polymer powder are particularly useful for adhering or consolidating substrates from the group of the natural and synthetic fiber materials. Useful fibers include all raw materials used in the relevant non-woven industry: polyester, polyamide, polypropylene, polyethylene, glass, ceramic, aramid, viscose, carbon, cellulose, cotton, wool or wood fibers and also blends thereof.
The choice of fiber material is not subject to any restriction or preference. The fiber material can be used in the form of fibers, yarns, mats, scrims or as woven textiles (wovens). Preference is given to mats or scrims of polyester, polyamide, polypropylene, polyethylene, aramid, carbon, glass, cellulose, cotton, wool or wood fibers.
Fiber bonding generally utilizes 1 to 50% by weight of bonding powder (phenolic resin +polymer powder), but preferably, 5 to 35% by weight, most preferably, 15 to 30% by weight, in each case based on the total weight of the textile sheet material.
The fiber materials may be consolidated with the phenolic resin composition modified by an addition polymer according to the procedures customary in non-woven technology:
The fibers are blended with the polymer powder-modified phenolic resin compositions in an air stream and the fiber/powder blend is laid down according to the conventional processes of non-woven technology, optionally, carding of the fiber/powder blend, to form a fiber bed. The curing of the powder takes place in the course of an immediately subsequent oven passage, optionally with the use of superheated steam. The oven temperature depends on the residence time of the web in the oven and on the corresponding curing kinetics. The action of shearing forces promotes full curing.
The webs are customarily heated at 110xc2x0 C. to 180xc2x0 C., preferably 120xc2x0 C. to 170xc2x0 C., especially 130xc2x0 C. to 160xc2x0 C., for a period of 30 seconds to 5 minutes, preferably 1 to 4 minutes, especially, 1.5 to 3 minutes. The thus bonded webs may subsequently, if desired, be pressed under a pressure of 1 to 100 bars in a hot press to form shaped articles. This is likewise optionally accomplished with the aid of superheated steam. Mold temperatures are between 150xc2x0 C. and 250xc2x0 C. coupled with in-press residence times of 0.25 to 10 minutes.
In one possible embodiment, the polymer powder and the phenolic resin powder are sprinkled as a blend or in succession, in any desired order into a previously laid-down fiber bed, and incorporated into the fiber bed by shaking or needling. If desired, this may be followed by a second web formation step in which an intimate mixture of fibers and powder is laid down as a further web. The powder is cured by the temperature being raised, optionally with the employment of pressure and superheated steam under the above-mentioned conditions.
It is also possible to laminate two or more non-wovens or wovens to each other or one another. To this end, ready-made fiber webs or other substrates are treated with the phenolic resin powder and the polymer powder, subsequently combined at their large surfaces and cross-linked under the above-mentioned conditions, optionally with the additional employment of pressure and superheated steam, at an elevated temperature.
The combination of polymer powder and phenolic resin powder is useful for producing shaped articles from fiber materials and also for producing precursors to such shaped articles, these semi-finished products being known as waddings. Furthermore, it can be employed in bonding the waddings, for example, cushioning, insulating and filter waddings. Preference is further given to laminates or clad products where two identical or two different fibrous structures spread out in sheet fashion are adhered to each other. Examples are insulants in automotive engineering which are composed of reclaimed cotton and which are durably laminated with a surface mat. Preference is also given to laminates where fibrous structures are adhered to non-fibrous substrates. Examples are the adhering of glass fibers onto decorative surface films or panels in the sector of building insulation or the adhering of wovens or other webs to leather in the shoe industry (shoe caps). Preference is further given to laminates of plural superposed fabric layers which are bonded by means of the procedure according to the invention. Examples are two- or more highly layered fabric plies of glass, carbon and/or aramid fiber, which are processible into moldings, if desired.
As well as accelerating the curing, the procedure of the invention provides less brittle moldings owing to the fraction of pulverulent addition polymers.

Process for producing fast curing molding compounds bonded with phenolic resin


A pre-event connectome of a subject brain is accessed, the pre-event connectome defining i) first functional nodes in the subject brain and ii) first edges that represent connections between the first functional nodes before the subject has undergone an event. A post-event connectome of the subject brain is accessed, the post-event connectome defining i) second functional nodes in the subject brain and ii) second edges that represent connections between the second functional nodes after the subject has undergone the event. A connectome-difference map data is generated that records the difference between the pre-event connectome and the post-event connectome. An action is taken based on the connectome-difference map data.

Medical imaging includes the technique and process of creating visual representations of the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to reveal internal structures hidden by the skin and bones, as well as to diagnose and treat disease. Medical imaging also establishes a database of normal anatomy and physiology to make it possible to identify abnormalities.

Medical imaging with functional architecture tracking


An electronic shifter for shifting a bicycle gear mechanism between a plurality of gears and using a relative shifting method. The shifter includes a stationary member mountable on a handlebar of the bicycle and a rotatable member rotatable with respect to the stationary member to define predetermined positions of the members with respect to each other. An electrical switch is operatively connected to the rotating member for generating a shift signal in response to the rotating member rotating from one predetermined position to another predetermined position.

This invention relates to electronic shifters for bicycles and, more particularly, to an electronic shifter using relative index shifting.
It is known in the art relating to bicycles to provide electronic shifters to actuate a gear shifter to shift a gear mechanism between gears. The system usually includes a controller or microprocessor for generating a shift signal in response to the rider manually selecting a upshift or downshift. The method of shifting may be based on absolute index shifting or relative index shifting. With absolute indexing, the shifting system has a predetermined number of gears which corresponds to an equivalent number of shift inputs that the user depresses in order to select a gear. A simple form of the electronic absolute shifter has a specific shift input button for each gear. A problem associated with such a configuration is that when one of the shift input button does not match the corresponding gear, the system does not function properly. To prevent this type of malfunction, a more complex electronic system is needed. This system requires several additional components such as a device for determining the current gear; additional computer programming to prevent miscommunication between the shift input and the actual gear; and a more costly sophisticated microprocessor to coordinate such tasks. A robust absolute shifting system requires additional complexity and costs.
In a relative indexing shifting system, each gear does not need a specific shift input rather each input represents only a generic shift. Each time the shift input is depressed the system shifts relative to the current gear. The command is not, xe2x80x9c1 to 3 . . . 3 to 5 . . . 5 to etc., but rather a more simple command, xe2x80x9cup . . . up . . . or down . . . down . . . , etc.xe2x80x9d This type of relative index shifting has several disadvantages. For instance, the electronic shifter may include two shift buttons, one for upshifting and the other for downshifting. This type of shifter requires the rider too rapidly push the buttons to perform multiple shifts. Another type of relative shifter is a return-to-center shifter wherein the shifter has three positions, a center, a forward twist and a reward twist. The rider twists the shifter forward or backward to shift and then the shifter returns to center under spring load. The disadvantage with this configuration is that the rider must perform twist-release, twist-release motions to perform multiple shifts. Therefore, there is a need to provide an electronic shifter that uses the simplicity of relative shifting and provides an ergonomic configuration that allows the rider to perform multiple shifts with a single movement.
The present invention provides an electronic shifter for shifting a bicycle gear mechanism between a plurality of gears. The shifter includes a stationary member mountable to a handlebar of the bicycle and a rotating member rotatable with respect to the stationary member to define predetermined positions of the members with respect to each other. The predetermined positions correspond to the plurality of gears. An electrical switch is operatively connected the rotating member for generating a shift signal in response to the rotating member rotating from one predetermined position to another predetermined position.
In one embodiment of the present invention, the rotating member may rotate about an axis perpendicular to the handlebar. Alternatively, the rotating member may rotate about an axis coaxial of the handlebar. The stationary member includes a first plurality of detents disposed on a surface of the stationary member. The rotating member includes a second plurality of detents disposed on a surface of the rotating member. The second plurality of detents are engagable with the first plurality of detents. The configuration of the first and second plurality of detents is such that upon rotation of the rotating member the first and second plurality of detents disengage to allow rotation of the rotating member. A resilient member biases the second plurality of detents to engage with the first plurality of detents. Rotation of the rotating member in a first direction causes the gear mechanism to be shifted in an upshift direction and a rotation of the rotating member in a second direction causes the gear mechanism to shift in an downshift direction.
These and other features and advantages of the invention will be more fully understood from the following description of certain specific embodiments of the invention take together with the accompanying drawings.