Circuits, methods, and apparatus that allow sports or other equipment, such as gym or other cardio equipment, to write data to a media player. Examples further provide the uploading of this data to a computer and third-party website. To monitor progress, the third-party website can be used to track workout data over time. The third party-website can also collect data from other users, which is particularly useful for providing a competitive environment. This data can then be graphically displayed in various ways to provide encouragement.

Portable media players have become very popular the past few years and their market penetration shows no signs of abating. People use them when walking, driving, and commuting by bus or train. They are also particularly useful as a distraction or source of entertainment when working out. People often bring these to a gym or similar location to use while exercising.
While exercising, many people like to keep track of their progress. For example, the distance "traveled" while on a treadmill may be recorded and progress over time monitored. This can provide positive feedback when progress is made; it can also provide encouragement to improve when efforts have been somewhat lacking.
This data is typically recorded using a clipboard and paper or notebook. However, this is somewhat time consuming. Because people often carve a few minutes out of their day to exercise, it is not desirable to lose time keeping track of this data; they may need to quickly return to work or home. Also, since it does not happen automatically, such record keeping can become spotty at times.
The portable media players that are often found at the gym are capable of carrying data. Unfortunately, there is currently no simple way to transfer workout data to them. That is, there is no easy way to transfer data from equipment in the gym to a portable media player.
Further, it would be desirable to store other types of data using a media player. For example, heart rate, blood pressure, blood oxygen level, and other monitors and sensors provide data that could be collected and stored.
Thus, what is needed are circuits, methods, and apparatus that allow sports and other types of equipment, such as the above-mentioned treadmill, to write data to a media player for record-keeping and other purposes.

Interfacing portable media devices and sports equipment


Active acne and acneiform scars are treated by topical application of a composition containing lipoic acid and/or a lipoic acid derivative such as dihydrolipoic acid, a lipoic or dihydrolipoic acid ester, a lipoic or dihydrolipoic acid amide, a lipoic or dihydrolipoic acid salt, and mixtures of any of these to reduce erythema, pore size, and scarring. Topical application of lipoic acid and/or a lipoic acid derivatives are advantageously used with at least one adjunct ingredient such as a retinoid, an antibiotic, or benzoyl peroxide conventionally used for acne, alone or in combination with dimethylaminoalcohol, an xcex1-hydroxy acid such as glycolic acid, a tyrosine, tocotrienol, and/or a fatty acid ester of ascorbic acid. One preferred embodiment contains a combination of lipoic acid, an xcex1-hydroxy acid, and dimethylaminoalcohol.

Not Applicable
1. Field of the Invention
This invention relates primarily to methods and compositions for the treatment of acne vulgaris. Acne is the most common pustular condition of the skin, disfiguring afflicted persons with inflammatory and noninflammatory lesions (including pustules, papules and comedones) during the active phase, and with atrophic scars afterwards. It occurs most commonly in teenagers, but is not confined to adolescents, as increasing numbers of persons aged  greater than 20 years are seeking advice on treatment for acne (Brogden, R. N., and Goa, K. L., Drugs, 1997, 53: 511-519; this reference and others cited below are hereby incorporated herein in their entireties by reference). Although acne is generally considered to be self-limiting, its social effects can be substantial, and it may have its most severe effects on the psyche (ibid.). In about 60% of teenagers, disease severity is sufficient for them to self-medicate with proprietary preparations, or seek medical advice.
Acne is a multifactorial disease affecting the pilosebaceous units of the skin. Each unit consists of a large, multilobed sebaceous gland, a rudimentary hair and a wide follicular canal lined with stratefied squamous epithelium. They are found over most of the body surface but are largest and most numerous on the face, chest, and upper back. Normally, desquamated follicular cells are carried to the surface by the flow of sebum. Under the abnormal circumstances of acne vulgaris, an abnormal desquamination process provokes increased sloughing of the epithelium, which becomes more cohesive because of defective keratinization. This process causes blockage of the follicular orifice with accumulation of dead cells. Androgen stimulates the undifferentiated hormonally responsive cells making up the outer layer of the sebaceous gland lobule to divide and differentiate. Sebum production favors proliferation of the anaerobe Propionibacterium acnes, which is a normal commensal to the pilosebaceous unit, which can elicit hypersensitivity responses in acne.
The basic lesion of acne is the microcomedo. Accumulation of sebum and keratinous debris results in a visible closed comedo, or whitehead, and its continued distension causes an open comedo, or blackhead. The dark color of blackheads is due to oxidized melanin. Blackheads and microcysts are noninflammatory lesions of acne, but some comedones evolve into inflammatory papules, pustules, or nodules, and can become chronic granulomatous lesions. The initial inflammatory cell in an acute acne papule is the CD4+T lumphocyte. Duct rupture is not a prerequisite for inflammation, which is due to the release of pro-inflammatory substances from the duct. When inflammation develops, neutrophil chemotaxis occurs. These neutrophils secrete hydrolytic enzymes that cause further damage and increased permeability of the follicular wall. In pustules, neutrophils are present much earlier. More persistent lesions exhibit granulomatous histology that can lead to scarring.
The aims of treating acne are to prevent scarring, limit disease duration, and reduce the social and psychological stress that affects many patients, particularly teenagers. Conventional treatment is directed at correcting the three major factors that seem to cause acne: (1) androgenic stimulation of the sebaceous glands and increased sebum production; (2) abnormal keratinization and impaction in the pilosebaceous canal causing obstruction to sebum flow; and (3) proliferation of P. acnes. Thus, topical agents that remove comedones, such as topical retinoids are particularly effective because they normalize desquamination within the follicular orifice, which allows the sebum to flow freely onto the surface of the skin; adalpalene, tretinoin, and tazarotene have been shown to have efficacy in treating mild to moderate acne, but all three have reported to have skin-irritating side effects including erythema, pruritis, burning/stinging, and scaling/flaking (Physicians"" Desk Reference(copyright), 54th ed. 2000, pp 502-503, 1104-1105, and 2139-2142, hereinafter referred to as xe2x80x9cPDRxe2x80x9d). Topical vitamin A preparations and benzoyl peroxide have been used to treat acne for some time. However, it has been recently reported that benzoyl peroxide seems to induce free radical production that can produce skin changes that qualitatively resemble ultraviolet B damage, e.g., increases in epidermal thickness, and deleterious changes in elastin and glycosaminoglycan content (Ibbotson, S. H., et al., J. Inves. Derm., 1999, 112: 933-938). Topical and oral antibiotics (especially tetracycline, erythromycin, and clindamycin) are sometimes prescribed for patients with inflammatory papules and pustules; but, in addition to the undesirability antibiotic overuse in general, disadvantages to such treatments include phototoxicity and interactions with other medications. Other factors that play a role in exacerbating acne, including oil-based cosmetics and some drugs (e.g., androgenic hormones, high-progestin birth control pills, systemic corticosteroids, and iodide- and bromide-containing agents) are often minimized during acne treatment.
Human sebum contains an unusual mixture of lipids, with the major lipid classes being triacylglycerides (TAG, conventional fat, ≈40 to 60%), wax esters (≈19 to 26%), and squalene (≈11 to 15%), but at least 15 different neutral and polar lipids have been identified in human sebaceous glad tissue (Downie, M. M. T., and Kealey, T., J. Invest. Derm., 1998, 111: 199-205). Recent studies have shown that people with acne have abnormal sebum secretions in that the ratios of essential fatty acids in sebaceous triacylglycerides (TAG, conventional fat) are skewed, as are the proportions of TAG, squalene and wax esters. It has been hypothesized that the viscosity and irritant level of these substances contribute to sebum obstruction and rupture of pilosebaceous units observed in acne. Lipogenesis in human sebaceous glands varies depending upon the metabolic state of the cells, glandular fluctuations, and the presence or absence of different substrates or other substances effecting competition between sterol and TAG pathways (Downie and Kealey, cited above). It would be desirable to utilize this biochemical information to devise alternate treatments for acne.
It would also be desirable to not only treat acne vulgaris manifested by the symptoms of pustule, papule, and comedone formation described above, but also minimize scar formation and treat atrophic acneiform scars left after resolution of the active phase. Scars result from the formation of granulation tissue and matrix formation following inflammation. (For a review, see Sahl, W. J., and Clever, H., Internat. J. Derm., 1994, 33: 681-691 (part I) and 763-769 (part II), and parent case U.S. Pat. No. 5,965,618 to Perricone cited above). Atrophic scars of the face left after acne have been traditionally treated with invasive methods such as scar revision, laser ablation, and chemical peels. Non-invasive techniques have consisted of topical application of tretinoin, as well as the application of estrogens and xcex1-hydroxy acids. None of these non-invasive procedures have been effective enough to justify widespread use as a therapy.
2. Description of Related Art
Lipoic acid was originally identified as a bacterial growth factor present in the water-soluble fraction of liver and yeast. It was found to be necessary for the oxidative decarboxylation of pyruvic acid by Streptococcus fecalis and for the growth of Tetrahymena gelii, and replaced acetate for the growth of Lactobacillus casei. Subsequent research showed that lipoic acid was a growth factor for many bacteria and protozoa, and it served as a prosthetic group, coenzyme, or substrate in plants, microorganisms, and animal tissues, participating in a variety of metabolic processes including acyl transfer reactions unction determined that it is a co-factor for xcex1-keto-dehydrogenase complexes. Its reduced form, dihydrolipoic acid (herein sometimes referred to as DHLA), is a potent sulfhydryl reductant. In aqueous systems, both lipoic acid and DHLA exhibit antioxidant actions (reviewed by Packer, L., et al., Free Rad. Biol. Med., 1995, 19: 227-250 (1995)). Lipoic acid has been shown to maintain microsomal protein thiols, protect against hemolysis, and protect against neurological disorders. The protective effect of dietary supplementation of lipoic acid against ischemia/reperfusion injury in the Langendorff isolated heart model has also been demonstrated lipoic acid has been suggested for treating systemically, or as adjuvant systemic medication for, liver cirrhosis, atheroscilerosis, diabetes, neurodegenerative diseases, heavy metal poisoning, mushroom poisoning and Chagas disease.
A couple of recent references have suggested that lipoic acid might be useful in dermatological compositions. In a 1988 Japanese patent publication (JP 63008315), lipoic acid in cosmetics at concentrations of 0.01% to 1%, preferably 0.05% to 0.5%, or in topical xe2x80x9cquasi-drugsxe2x80x9d at concentrations of 0.1% to 1.5%, preferably 0.5% to 1.0%, were suggested for inhibiting tyrosinase, and thus melanin formation, to whiten skin.
In 1995, Rawlings, et al., disclosed a composition and method for xe2x80x9cimproving or preventing the appearance of dry, flaky wrinkled, aged, photodamaged skin and treating skin disordersxe2x80x9d (U.S. Pat. No. 5,472,698, column 2, lines 51 to 54) using a synergistic combination of serine and/or N-acetyl serine and a thiol, an xe2x80x9cS-esterxe2x80x9d, and/or a disulfide (id., lines 28 to 33). Lipoic acid was mentioned as encompassed by the latter ingredient (column 3, lines 29 to 30), but the terminology in the patent was confusing because thiols and S-esters were disclosed as preferable over disulfides such as lipoic acid. And the focus of the patent was stimulation of sphingolipid synthesis in skin, with lipoic acid shown to be the same as control compositions, and have no effect in combinations without serine.
A year later, Weischer, et al., (in U.S. Pat. No. 5,569,670), pharmaceutical compositions containing a synergistic combination of xcex1-lipoic acid and/or dihydrolipoic acid with specific enantiomers of these, together with some vitamins, including C and E (column 1, lines 3 to 15), were disclosed as useful, primarily for treating diabetes (see the claims). However, anti-inflammatories (abstract, line 8 and column 2 at line 16) as well as treatments for retroviruses and other pathological conditions were included, with an emphasis on veterinary applications (column 13, lines 42 to 62). In a test model for inflammation (observing rat edema), the R-enantiomer of lipoic acid was superior to lipoic alone or to vitamin E alone (column 3, lines 37 to 40). Suggested administration was oral, parenteral or intravenous (column 7, line 31 to end, et seq.), preferably oral (column 11, line 42), but application to skin and mucous membranes was mentioned (column 12, lines 58 to 60). An ointment was disclosed in Example 6; the others described suppositories, capsules, ampules, and tablets.
Similarly, U.S. Pat. No. 5,693,664 to Wessel, et al., from the same research group, was directed to diabetes treatments, particularly where insulin resistance is observed (column 1, lines 10 to 14 and the claims) by use of the R-enantiomer of xcex1-lipoic acid. Again, one enantiomer, not a racemate, was employed (column 6, lines 18 to 19). Indeed, the S-enantiomer decreased the effect of insulin in an experimental study reported (column 3, lines 61 to 65). Suggested adminstration was primarily oral (column 6, lines 61 to 66), though parenteral and intravenous are mentioned (ibid., and column 3, lines 7 to 8).
U.S. Pat. No. 5,728,735 to Ulrich, et al., again from the same group, stressed use of an enantiomer (column 1, lines 28 to 54), particularly the R-enantiomer (see the claims), and not a racemate, for combatting pain and inflammation in a variety of conditions (id., lines 58 to 59; inflammations are listed in column 5, line 64 to column 6, lines 9 and include neurodermatitis and psoriasis). Suggested administrations were oral, intravenous, or infusions (column 3, lines 28 to 30, 51, 62 to 63 and 65), but solutions and emulsions for topical application were mentioned (column 6, lines 29 to 34 and 65 to 68, and column 8, lines 16 to 18). Only tablets and ampules were illustrated. All the reported findings of the group are complicated by the fact that the metabolic effects of the R- and S-enantiomers are now known to be different, as are the enzymes that process the enantiomers in cytosolic and mitrochondrial systems (Haramaki, N., et al., Free Rad. Biol. Med. 22: 535-542 (1997)). Moreover, different stereospecific reduction by intact cells and tissues has also been observed (ibid.).
More recently, Perricone suggested the use of lipoic acid in dermatological compositions for the treatment of skin damage, particularly inflammation and aging (U.S. Pat. No. 5,709,868), and also for the treatment of scars, particularly for hypertrophic and keloid scars (U.S. Pat. No. 5,965,618). As explained in those patents, the antioxidant activity of lipoic acid appears to prevent free radical damage to cells and cell components. Modulation of the activation of transcription factor AP-1 by lipoic acid may also affect the activity of matrix metaloproteinases, allowing collagen remodeling which is necessary for scar improvement.
Inflammation in skin is mediated by several active chemicals and metabolites of arachidonic acid. Arachidonic acid is oxidized by cyclo-oxygenase and lipoxygenase to active metabolites such as the leukotrienes and 5- and 12-hydroxyeicosatetraenoic acid (HETES). Within the arachidonic acid cascade, many free radicals are generated, which both perpetuate and magnify the inflammatory cascade, resulting in skin damage and manifested clinically as erythema. The redox state of the cell determines gene expression. Transcription factor nuclear factor kappa-B (NFxcexa-B) and others are affected by the redox state of the cell. When the cell undergoes oxidative stress, i.e., ultraviolet radiation, ionizing radiation, infection, and free radicals created by metabolism, the inhibitory fraction of NFxcexa-B is dissociated from the molecule. Once the inhibitory fraction is dissociated from the NFxcexa-B molecule, it then migrates to the nucleus of the cell, begins transcription, and inflammatory mediators, including cytokines, are produced. AP-1, a transcription factor, appears to be activated bimodally, i.e., both under oxidation and reduction, resulting in matrix remodeling.
It is an objective of this invention to provide compositions and methods for the treatment of acne vulgaris, both during the active phase, and for acneiform scars afterwards, It is a corresponding objective to alleviate the negative social and psychological impacts frequently suffered by persons afflicted with acne. Facial lesions and scars are one of the strongest forces driving the cosmetic industry. It would be desirable to have new and improved methods for treating acne, as it is so widely observed in the population, particularly among teenagers who are especially sensitive about their appearance.
It is another and more specific objective of the invention to provide topical compositions and methods for acne lesion and acne scar treatment based upon the application of compositions containing lipoic acid and/or lipoic acid derivatives to skin areas disfigured by acne. Preferred embodiments further employ adjunct ingredients.
These and other objectives are accomplished by the present invention, which provides compositions and methods for the treatment of acne vulgaris, and improvements of currently employed therapies, which comprise topical application to skin areas exhibiting acne of an effective amount of lipoic acid, lipoic acid derivatives or mixtures thereof, typically in association with a dermatologically acceptable carrier. In most preferred embodiments, at least one other adjunct ingredient is included in the treatment or composition. Adjunct ingredients include, but are not limited to, xcex1-hydroxy acids such as glycolic and/or lactic acid; tocotrienols; fatty acid esters of ascorbic acid such as ascorbyl palmitate; tyrosine; antibiotics such as erythromycin, clindamycin, or tetracycline; retinoids such as tretinoin, adapalene, or tazarotene; or methyl- or ethyl-aminoalcohols such as dimethylaminoethanol. Benzoyl peroxide is included in some compositions. Adjunct ingredients enhance the efficacy of the treatment, and minimize or eliminate skin irritation to perilesional areas. Use of compositions of the invention are additionally beneficial in minimizing the adverse effects of surgical acne procedures such as dermabrasion, laser ablation, scar revision, and chemical peels.
The amount of lipoic acid or derivative thereof (hereinafter referred to collectively as lipoic acid or xe2x80x9cLAxe2x80x9d for ease of reference) necessary to treat acne is not fixed per se, and necessarily is dependent upon the identity and form of lipoic acid employed, the amount and type of any adjunct ingredients employed, the user""s skin type, and the severity and extent of the acne and/or acneiform scars. In some typical embodiments, the composition contains from about 0.1% to about 7 weight %, lipoic acid, more narrowly from about 0.25% to about 5 weight %. In one embodiment, about 2% to 5% lipoic acid is employed. The amount of adjunct ingredient or ingredient combination varies with what is employed, but typical concentration ranges vary from about 0.01% to about 10%, and in many cases from about 0.025% to about 7% by weight, depending upon the identity of the ingredient or ingredient combination.
This invention is based upon the finding that lipoic acid and/or its derivatives are useful for the treatment of acne vulgaris in the active phase and for acneiform scars. It has been surprisingly found that lipoic acid applied to the faces of persons with acne not only reduces erythema and acneiform scars, but also reduces pore size, and the beneficial effects increase over time. Moreover, lipoic acid and/or its derivatives provide surprising benefits when used with currently employed acne medications as adjunct ingredients because skin irritant side effects are minimized or eliminated, and other adjunct ingredients not heretofore suggested as acne medications improve the overall beneficial effects of LA compositions.
As used herein, the term xe2x80x9cacnexe2x80x9d includes all types of acne in all stages, including acne vulgaris observed in adolescents, acne observed in endocrinologic conditions characterized by excess androgen secretion, and the like, in the active inflammatory (pustule-, papule-, comedone-forming) and noninflammatory (blackhead- and cyst-forming) phases, and post-inflammatory (healing, scarring, and scarred) phase. The term xe2x80x9clipoic acidxe2x80x9d encompasses thioctic acid (1,2-dithiolane-3-pentanoic acid; 1,2-dithiolane-3-valeric acid), C8H14O2S2, formula weight 206.32, and its reduced form, dihydrolipoic acid. It has been variously known as acetate replacing factor, protogen A, and pyruvate oxidation factor. As mentioned above, for convenience, as used herein, where the properties and advantages of xe2x80x9clipoic acidxe2x80x9d (or LA) are discussed as an active ingredient in the practice of the invention, both lipoic acid and its derivatives are encompassed. xe2x80x9cLipoic acid derivativesxe2x80x9d include thioctic acid esters, particularly alkyl esters such as fatty acid esters, amides, particularly those isolated from or mimicking naturally occurring lipoamides, salts, particularly alkali metal salts, anhydrides and specifically includes the reduced form, dihydrolipoic acid and its esters, amides and salts. One particularly efficacious derivative that exhibits increased cellular uptake and biological activity useful in the practice of the invention is N,N-dimethyl,N-2-amidoethyl lipoate recently described by Sen, C. K., et al. (Free Radical Biol. Med., 1998, 25: 89) and called lipoic acid plus (LA-Plus). Since lipoic acid is both fat- and water-soluble, it is an advantage of the invention that it can be used in either lipid or aqueous-based compositions, and it readily crosses cellular membranes and disperses in extracellular and intracellular tissue components. Derivatives may also include those involving other reactive groups known to those skilled in the art. As used herein, the term xe2x80x9cderivativesxe2x80x9d includes metabolic precursors of lipoic acid. Where lipoic acid derivatives are employed, they must be functionally equivalent to lipoic acid.
As mentioned above, lipoic acid is fat-soluble. Therefore, lipoic acid preparations can be applied neat to skin tissue. It is an advantage of the invention that the active compound is fatty so that it physically contributes to the lubrication of affected skin areas to which it is applied.
However, only effective amounts of lipoic acid are needed to treat acne and acneiform scars, so generally topical application to exposed or affected skin sites is accomplished in association with a carrier, and particularly one in which the active ingredient is soluble per se or is effectively solubilized (e.g., as an emulsion or microemulsion). Where employed, the carrier is inert in the sense of not bringing about a deactivation of the lipoic acid or derivative, and in the sense of not bringing about any adverse effect on the skin areas to which it is applied.
Suitable carriers include water, alcohols, oils and the like, chosen for their ability to dissolve or disperse lipoic acid and any other ingredients used in the treatment. Generally, even low concentrations of active ingredients in a carrier are suitable, depending upon the application regimen and adjunct ingredients employed. Many embodiments contain from about 0.1% to about 7% by weight, more narrowly from about 0.25% to about 5% by weight, LA. Many embodiments contain more than 1 weight % lipoic acid and/or lipoic acid derivative, e.g., from about 1.1% to about 3 to 5 weight % LA. One efficacious embodiment contains from about 2% to about 5% by weight. Examples are illustrated hereafter.
While the carrier for lipoic acid can consist of a relatively simple solvent or dispersant, it is generally preferred that the carrier comprise a composition more conducive to topical application, and particularly one which will form a film or layer on the skin to which it is applied so as to localize the application and provide some resistance to perspiration and/or one which aids in percutaneous delivery and penetration of the active ingredients into lipid layers of the scarred area. Many such compositions are known in the art, and can take the form of lotions, creams, gels or even solid compositions (e.g., stick-form preparations). Typical compositions include lotions containing water and/or alcohols and emollients such as hydrocarbon oils and waxes, silicone oils, hyaluronic acid, vegetable, animal or marine fats or oils, glyceride derivatives, fatty acids or fatty acid esters or alcohols or alcohol ethers, lanolin and derivatives, polyhydric alcohols or esters, wax esters, sterols, phospholipids and the like, and generally also emulsifiers (nonionic, cationic or anionic), although some of the emollients inherently possess emulsifying properties. These same general ingredients can be formulated into a cream rather than a lotion, or into gels, or into solid sticks by utilization of different proportions of the ingredients and/or by inclusion of thickening agents such as gums or other forms of hydrophillic colloids. Such compositions are referred to herein as dermatologically acceptable carriers. Most preferred for skin are those carriers which are fat-soluble, i.e., those which can effectively penetrate skin layers. And in embodiments employing lipoic acid with at least one other conventional acne medication or other adjunct ingredient, one or more of the active ingredients may be encapsulated to increase product shelf life and preserve maximal activity.
As has been mentioned, most preferred embodiments of this invention contain at least one other adjunct ingredient in addition to lipoic acid. Indeed, it is an advantage of the invention that some adjunct ingredients are conventional acne medications. Lipoic acid not only augments their effects, but minimizes or eliminates their side effects. Adjunct ingredients include, but are not limited to, not only retinoids, topical antibiotics, and benzoyl peroxide conventionally used in acne treatments, but also methyl-/ethyl-aminoalcohols, xcex1-hydroxy acids, tyrosine tocotrienols, and fatty acid esters of ascorbic acid.
Retinoids useful as adjunct ingredients with LA include commercially available adapalene, tazarotene and/or tretinoin described by Brogden and Goa and the PDR cited above. Adapalene, for example, is currently sold as a gel or solution marketed as Differin(copyright). Tretinoin can be obtained as a cream, gel or encapsulated microsphere marketed as Avita(copyright), Renova(copyright), or Retin-A(copyright). Tazarotene is marketed as a Tazorac(copyright) gel. Effective formulations typically contain from about 0.025% to about 0.1% by weight retinoid or retinoid mixture with LA concentrations set out above. Lipoic acid compositions can either contain at least one retinoid, or be applied before, during, or after treatment with at least one retinoid. It is an advantage of the invention that use of lipoic acid in conjunction with a retinoid in treatments employing retinoids provides a method for treating acne using less retinoid than would be required if a retinoid is used alone, because topical application of retinoids results in skin irritation in some patients. As set out in the PDR sections cited above, even at recommended frequency and dose levels, typically up to about 10% of patients complain of inflammation, swelling, and burning sensations when using products containing retinoids (including control patients who have no acne), but acne patients tend to overuse the medications. Lipoic acid can reduce this amount and the duration of drug use in patients presenting acne conditions warranting the beneficial normalizing desquaminating properties that retinoids can provide, and alleviate side effects. Preferred compositions of the invention also minimize or eliminate skin irritation, particularly in areas surrounding acne lesions.
Lipoic acid may also be used in combination with topical or oral antibiotics such as tetracycline, clindamycin, and erythromycin sometimes used for acne cases, particularly for patients with inflammatory papules and pustules. Lipoic acid may be added to an antibiotic preparation, or applied before, during, or after antibiotic treatment. As with retinoid therapy, an advantage of using lipoic acid with antibiotics in cases where they might be efficacious is that a lower antibiotic dose or a shorter antibiotic regimen may be employed. It is now recognized that prevalent use of antibiotics in general is undesirable, and long-term use of antibiotics can cause nausea, gastrointestinal upset, phototoxicity, enhanced susceptibility to yeast infection, and interactions with other medications. Use of lipoic acid advantageously minimizes the amount of antibiotic necessary to cause improvement in patients presenting with an extreme inflammatory phase of acne.
Adjunct ingredients not previously suggested for acne are also efficacious as ingredients with LA in the practice of the invention. Among these are methyl- and ethyl- derivatized lower amino alcohols. These include methyl- and ethyl-amino alcohols such as dimethylaminoethanol, monomethylaminoethanol, diethylaminoethanol, monoethylaminoethanol, their propanol and butanol counterparts (all isomers of monomethylaminopropanol, dimethylaminopropanol, monoethylaminopropanol, diethylaminopropanol, monomethylaminobutanol, dimethylaminobutanol, monoethylaminobutanol, and diethanolaminobutanol), and derivatives acylated with organic acids, particularly the lower (C1 to C3) carboxylic acids such as acetic acid because these esters are less bulky, and others set out in U.S. Pat. No. 5,554,647 to Perricone such as para-chlorophenylacetic acid esters. Dimethylaminoethanol is used in one embodiment. Typical amounts of lower amino alcohols such as dimethylaminoethanol employed in LA compositions of the invention range from about 0.5% to about 5% by weight, more narrowly from about 2% to about 3% by weight.
In some embodiments xcex1-hydroxy acids and/or their derivatives are included as adjunct ingredients. As used herein, the terminology xe2x80x9cxcex1-hydroxy acidxe2x80x9d has reference to and encompasses the general class of organic compounds containing at least one hydroxy group and at least one carboxyl group, and wherein at least one hydroxyl group is located on the xcex1-carbon atom. Typically, the compounds are organic acids having at least one carboxylic acid group and at least one hydroxyl group on the xcex1-carbon atom, and may contain other functional groups including additional hydroxyl and carboxylic acid moieties. Preferred xcex1-hydroxy acids and/or xcex1-hydroxy acid derivatives are less bulky structurally so that they penetrate the skin well, and thus have a backbone of from one to three carbon atoms such as those set out in parent case U.S. Pat. No. 5,965,618 at column 6 lines 4 to 29. In some preferred embodiments, glycolic and/or lactic acid or their derivatives are employed. Glycolic acid is especially efficacious. Preferred compositions contain effective amounts of xcex1-hydroxy acids. Typcal concentrations range from about 1% to about 10% by weight, more narrowly from about 3% to about 7%, by weight xcex1-hydroxy acid.
Tyrosine may be added as an adjunct ingredient to LA compositions of the invention in some embodiments. Typical concentrations range from about 0.05% to about 5%, more narrowly from about 1% to about 3%, by weight tyrosine. One particularly efficacious embodiment of the invention contains lipoic acid, glycolic or lactic acid, and dimethylaminoalcohol; another further contains tyrosine,
Fat-soluble fatty acid esters of ascorbic acid (vitamin C) may be added to the lipoic acid composition for treating acne in some embodiments. The more oxidation-resistant saturated fatty acid esters of ascorbic acid are preferred, including, but not limited to, ascorbyl laurate, ascorbyl myristate, ascorbyl palmitate, ascorbyl stearate, and ascorbyl behenate. Ascorbyl palmitate is used in one embodiment. As denoted herein, where fatty acid esters are described, e.g., ascorbyl stearate, compositions having predominantly that ester, e.g., predominantly stearate, are included. The esters may be prepared using hydrogenated oils or fats, or fractions thereof, and contain small amounts of another ester. Ascorbyl stearate prepared using canola, for example, commonly contain about 4% ascorbyl palmitate.
Tocotrienol may also be added to lipoic acid compositions of the invention, alone or in combination with an ascorbyl esters and/or xcex1-hydroxy acids or their derivatives in some embodiments. The term xe2x80x9ctocotrienolxe2x80x9d encompasses natural and/or synthetic counterparts of tocopherol (vitamin E) that bear unsaturated tails, and include, but not limited to, xcex1-, xcex2-, xcex3-, and xcex4-tocotrienols, tocotrienol P25, desmethyl-tocotrienol, didesmethyl-tocotrienol, their synthetic counterparts, their counterparts having methylated or demethylated chroman rings, tocotrienol-enriched fractions obtained from natural or synthetic sources, stabilized derivatives, and mixtures thereof, more fully described in parent case U.S. Pat. No. 5,965,618 at column 5, line 53 to column 7, line 23.
Any compositions of the invention employing LA as an active ingredient, alone or in combination with one or more adjunct ingredients, can also contain benzoyl peroxide, alone, or in combination with a vitamin A preparation conventionally used for acne treatments. One embodiment employs LA with tocotrienols and benzoyl peroxide. Lipoic acid can be applied together in the same composition with these other ingredients, or before, during, or after treatment with benzoyl peroxide and a tocotrienol. An advantage of using lipoic acid with benzoyl peroxide in any composition with or without one or more adjunct ingredients is that the deleterious skin damage caused by repeated administration of benzoyl peroxide reported by Ibbotson, et al., cited above is limited, as is perilesional skin irritation.
Lipoic acid can also be used advantageously as adjunct acne therapy before, during, or after surgical procedures for acne, such as dermabrasion, laser ablation, scar revision, and chemical peels typically used for extreme cases of acneiform scars. In this embodiment, it is especially efficacious in the post-physical treatment phases, as it helps heal the skin, prevent scarring, and may minimize the number and severity of the procedures to which scarred acne patients may be subjected.
While not wishing to be bound to any theory, it is possible that lipoic acid is efficacious in the treatment of acne because it is both fat- and water-soluble and readily disperses in cell membranes and other cellular components. Lipoic acid readily penetrates skin and is found in high concentrations in sebaceous gland tissue four hours after application. Because of its solubility, it is sometimes referred to as a universal antioxidant. It acts as a free radical scavenger and neutralizer, and prevents the cross-linking of cell membranes that is often seen in acne in its post-inflammatory phases. By the same token, LA modulation of free radicals and other oxidative species affects gene expression, including expression of nuclear factor xcexa-B (NF-xcexaB), nitric oxide synthetase and other mediators at all stages of proinflammation and inflammation. Lipoic acid""s alteration of lipid peroxidation, protein cross-linking, growth factor stimulation, and membrane permeability may explain its negative effect on the symptoms of acne.
Because of its activity within the pyruvate dyhydrogenase complex, lipoic acid has also been termed the metabolic antioxidant. Again, while not wishing to be bound to any theory, it may be that lipoic acid can boost energy production in sebaceous glands, which results in a more normal sebum production with triglycerides and lipids in normal ratios. Since lipogenesis in human sebaceous glands depends upon the metabolic status of the cells, the addition of lipoic acid by providing increased energy production would be therapeutic.
Generally in the practice of the method of the invention, the composition is topically applied to the affected skin areas in a predetermined or as-needed regimen either at intervals by application of a lotion or the like, it generally being the case that gradual improvements is noted with each successive application. Insofar as has been determined based upon clinical studies to date, no adverse side effects are encountered.
It is an adavantage of the invention that topical application of lipoic acid provides a simple, non-invasive, nontoxic, over-the-counter topical method for treating all phases of acne. Lipoic acid compositions decrease erythema observed with acne pustules, papules and whiteheads, and a marked decrease in lesion numbers. The effect is enhanced by use of adjunct ingredients such as dimethylaminoethanol, xcex1-hydroxy acids, and/or tyrosine. Lipoic acid compositions decrease pore size, minimizing sebum accumulation and keratinous debris that cause both whiteheads and blackheads observed in acne. Lipoic acid minimizes scar formation, and provides marked losses of scar borders and decreases in scar depth where scars have already formed. Topically applied lipoic acid also seems to fill in scar tissue, making it more equal to adjacent normal skin. Moreover, compositions containing lipoic acid with adjunct ingredients such as retinoids, xcex1-hydroxy acids, tyrosine, and/or dimethylaminoethanol, appear to successfully treat active acne lesions without harming surrounding skin tissue. And with these physical effects, persons using lipoic acid topical compositions experience a reducion in the social and psychological stress often associated with acne patients suffering facial disfigurements.


To accelerate the curing of epoxide resins by particular curing agents, i.e., polyamines, polyaminoamides, polycarboxylic acids, or polycarboxylic acid anhydrides, there is employed an aliphatic or araliphatic monocarboxylic acid group at least two halogen atoms chosen from fluorine and chlorine atoms, or a salt thereof, such as magnesium trifluoroacetate and magnesium trichloroacetate.

This invention relates to compositions for curing epoxide resins, to curable mixtures of these compositions and epoxide resins, and to cured products obtained by curing the aforesaid mixtures.
It is known that epoxide resins, i.e., substances containing on average more than one 1,2-epoxide group per molecule, may be cured by reaction with various classes of substances to form cross-linked, infusible, insoluble products having valuable technical properties. Typical curing agents include aromatic, aliphatic, heterocyclic, and cycloaliphatic polyamines and polyaminoamides, and polycarboxylic acids and their anhydrides. Some of these agents are suitable for curing at room temperature whilst others are suitable only at elevated temperatures. The chief drawback with curing agents at present in use is that they often cure the resin only slowly. The use of accelerators alleviates this drawback to some extent but the accelerating effect which the accelerators presently employed impart is relatively modest, particularly when amine curing agents are employed.
United States Patent Specification No. 3278305 discloses a process for the photochemical crosslinking of polymers which comprises exposing to actinic light selected portions of a photo-sensitive mixture containing a polymeric material carrying groups which are reactive with photochemically formed isocyanates and a polycarboxylic acid azide capable of forming crosslinks with the polymeric material. Among the polymeric materials mentioned are epoxide resins. It is stated that, under the influence of light, the polycarboxylic acid azides are probably converted into polyisocyanates. Compounds which are known to accelerate the photochemical conversion of the acid azide group into an isocyanate group, such as trichloroacetic acid, may be added to the photosensitive composition.
We have now found that certain fluorinated or chlorinated carboxylic acids and their salts very markedly accelerate the cure of epoxide resins by polyamines, polyaminoamides, polycarboxylic acids, and polycarboxylic acid anhydrides.
One aspect of this invention therefore comprises compositions, suitable for use as a curing agent for epoxide resins, consisting of
A. A POLYAMINE, A POLYAMINOAMIDE, A POLYCARBOXYLIC ACID, OR A POLYCARBOXYLIC ACID ANHYDRIDE, AND
B. AN ALIPHATIC OR ARALIPHATIC MONOCARBOXYLIC ACID OF 2 TO 8 CARBON ATOMS, BEARING ON THE CARBON ATOM ADJACENT TO THE CARBOXYL GROUP AT LEAST TWO HALOGEN ATOMS CHOSEN FROM FLUORINE AND CHLORINE ATOMS, OR A SALT THEREOF.
Another aspect of this invention comprises a curable composition consisting of
A. A POLYAMINE, A POLYAMINOAMIDE, A POLYCARBOXYLIC ACID, OR A POLYCARBOXYLIC ACID ANHYDRIDE,
B. AN ALIPHATIC OR ARALIPHATIC MONOCARBOXYLIC ACID OF 2 TO 8 CARBON ATOMS, BEARING ON THE CARBON ATOM ADJACENT TO THE CARBOXYL GROUP AT LEAST TWO HALOGEN ATOMS CHOSEN FROM FLUORINE AND CHLORINE ATOMS, OR A SALT THEREOF, AND
C. AN EPOXIDE RESIN.
A further aspect of this invention comprises a process for curing an epoxide resin which consists of forming a mixture of the epoxide resin, an effective (i.e., curing) amount of a polyamine, a polyaminoamide, a polycarboxylic acid, or a polycarboxylic acid anhydride as curing agent therefor, and an aliphatic or araliphatic monocarboxylic acid of 2 to 8 carbon atoms, bearing on the carbon atom adjacent to the carboxyl group at least two halogen atoms chosen from fluorine and chlorine atoms, or a salt thereof, and allowing or causing the mixture to cure.
The preferred halogenated acids are fluorinated or chlorinated, especially perfluorinated or perchlorinated, saturated aliphatic acids of from 2 to 6 carbon atoms, more particularly of from 2 to 4 carbon atoms, such as dichloroacetic, .alpha.,.alpha.-dichloropropionic, perfluoropropionic, and perfluoro-n-butyric acids. Trifluoroacetic acid and trichloroacetic acid are especially preferred.
The salt of the halogenated acid may be those of light or heavy metals, i.e., of metals of Groups IA, IB, IIA, IIB, IIIB, IVB, VB, VIB, VIIB, or VIII of the Periodic Table (as shown on p. 60-61 in Handbook of Chemistry, ed. Lange, Revised Tenth Edition, published by McGraw-Hill). The metals may be trivalent, e.g., chromic chromium, but preferably they are mono- or divalent, such as lithium, sodium, calcium, zinc, barium, copper, cobalt, nickel, manganese, vanadyl vanadium (VO.sup.2+), and magnesium, the lithium, sodium, calcium, and magnesium salts being particularly preferred for use with aromatic amines and the zinc, manganese, vanadyl, and magnesium salts being particularly preferred for use with aliphatic amines.
The salts may also be ammonium salts, including quaternary ammonium salts, or amine salts such as those of aromatic, aliphatic, or heterocyclic amines, preferably those amines having a basic strength, - log K.sub.1, of 5 or less. Typical such amines include mono-, di-, and tri-methylamine, mono-, di-, and tri-ethylamine, ethanolamine, the butylamines, enzylamine, 2-phenylethylamine, N,N-dimethylbenzylamine, ethylenediamine, piperazine, piperidine, bis(4-aminophenyl)methane, 3-ethyl-4,4'-diaminodiphenylmethane, and bis(3-ethyl-4-aminophenyl)methane.
Epoxide resins which may be employed in these compositions are preferably those containing groups of formula ##STR1## directly attached to atoms of oxygen, nitrogen, or sulphur, where either R and R.sup.2 each represent a hydrogen atom, in which case R.sup.1 denotes a hydrogen atom or a methyl group, or R and R.sup.2 together represent --CH.sub.2 CH.sub.2 --, in which case R.sup.1 denotes a hydrogen atom.
As examples of such resins may be mentioned polyglycidyl and poly(.beta.-methylglycidyl) esters obtainable by reaction of a compound containing two or more carboxylic acid groups per molecule with epichlorohydrin, glycerol dichlorohydrin, or .beta.-methylepichlorohydrin in the presence of an alkali. Such polyglycidyl esters may be derived from aliphatic polycarboxylic acids, e.g., oxalic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, or dimerised or trimerised linoleic acid; from cycloaliphatic polycarboxylic acids such as tetrahydrophthalic acid, 4-methyltetrahydrophthalic acid, hexahydrophthalic acid, and 4-methylhexahydrophthalic acid; and from aromatic polycarboxylic acids such as phthalic acid, isophthalic acid, and terephthalic acid.
Further examples are polyglycidyl and poly(.beta.-methylglycidyl) ethers obtainable by reaction of a compound containing at least two free alcoholic hydroxyl and/or phenolic hydroxyl groups per molecule with the appropriate epichlorohydrin under alkaline conditions or, alternatively, in the presence of an acidic catalyst and subsequent treatment with alkali. These ethers may be made from acyclic alcohols such as ethylene glycol, diethylene glycol, and higher poly(oxyethylene) glycols,propane-1,2-diol and poly(oxypropylene) glycols, propane-1,3-diol, butane-1,4-diol, poly(oxytetramethylene) glycols, pentane-1,5-diol, hexane-1,6-diol, hexane-2,4,6-triol, glycerol, 1,1,1-trimethylolpropane, pentaerythritol, sorbitol, and poly(epichlorohydrin); from cycloaliphatic alcohols such as resorcitol, quinitol, bis(4-hydroxycyclohexyl)methane, 2,2-bis(4-hydroxycyclohexyl)-propane, and 1,1-bis(hydroxymethyl)cyclohex-3-ene; and from alcohols having aromatic nuclei, such as N,N-bis(2-hydroxyethyl)aniline and p,p'-bis(2-hydroxyethylamino)diphenylmethane. Or they may be made from mononuclear phenols, such as resorcinol and hydroquinone, and from polynuclear phenols, such as bis(4-hydroxyphenyl)methane, 4,4'-dihydroxydiphenyl, bis(4-hydroxyphenyl) sulphone, 1,1,2,2-tetrakis(4-hydroxyphenyl)-ethane, 2,2-bis(4-hydroxyphenyl)propane (otherwise known as bisphenol A), 2,2-bis(3,5-dibromo-4-hydroxyphenyl)propane, and novolaks formed from aldehydes such as formaldehyde, acetaldehyde, chloral, and furfuraldehyde, with phenols such as phenol itself, and phenol substituted in the ring by chlorine atoms or by alkyl groups each containing up to nine carbon atoms, such as 4-chlorophenol, 2-methylphenol, and 4 -tert.butylphenol.
Poly(N-glycidyl) compounds include, for example, those obtained by dehydrochlorination of the reaction products of epichlorohydrin with amines containing at least two amino-hydrogen atoms such as aniline, n-butylamine, bis(4-aminophenyl)methane, and bis(4-methylaminophenyl)methane; triglycidyl isocyanurate; and N,N'-diglycidyl derivatives of cyclic alkylene ureas, such as ethyleneurea and 1,3-propyleneurea, and of hydantoins such as 5,5-dimethylhydantoin.
Examples of poly(S-glycidyl) compounds are di-S-glycidyl derivatives of dithiols such as ethane-1,2-dithiol and bis(4-mercaptomethylphenyl) ether.
Examples of epoxide resins having groups of formula I where R and R.sup.2 conjointly denote a --CH.sub.2 CH.sub.2 -- group are bis(2,3-epoxycyclopentyl) ether, 2,3-epoxycyclopentyl glycidyl ether, and 1,2-bis(2,3-epoxycyclopentyloxy)ethane.
Epoxide resins having the 1,2-epoxide groups attached to different kinds of hetero atoms may be employed, e.g., the N,N,O-- triglycidyl derivative of 4-aminophenol, the glycidyl ether-glycidyl ester of salicyclic acid, N-glycidyl-N'-(2-glycidyloxypropyl)-5,5-dimethylhydantoin, and 2-glycidyloxy-1,3-bis(5,5-dimethyl-1-glycidylhydantoin-3-yl)propane.
Epoxide resins in which some or all of the epoxide groups are not terminal may also be employed, such as vinylcyclohexene dioxide, limonene dioxide, dicyclopentadiene dioxide, 4-oxatetracyclo [6,2.1.0.sup.2,7.0.sup.3,5 ] undec-9-yl glycidyl ether, the bis(4-oxatetracyclo [184.108.40.206.sup.2,7.0.sup.3,5 ]undec-9-yl) ether of ethylene glycol, 3,4-epoxycyclohexylmethyl 3',4'-epoxycyclohexanecarboxylate and its 6,6'-dimethyl derivative, the bis(3,4-epoxycyclohexanecarboxylate) of ethylene glycol, 3-(3,4-epoxycyclohexyl)-8,9-epoxy-2,4-dioxaspiro [5,5] undecane, and epoxidised butadienes of copolymers of butadiene with ethylenic compounds such as styrene and vinyl acetate.
If desired, a mixture of epoxide resins may be used.
Preferred epoxide resins are polyglycidyl ethers, polyglycidyl esters, and N,N'-diglycidylhydantoins. Specific preferred resins are polyglycidyl ethers of 2,2-bis(4-hydroxyphenyl)propane, of bis(4-hydroxyphenylmethane, or of a novolak formed from formaldehyde and phenol, or phenol substituted in the ring by one chlorine atom or by one alkyl hydrocarbon group containing from one to nine carbon atoms, and having a 1,2-epoxide content of more than 0.5 equivalent per kilogram.
As examples of polyamines suitable for use as the curing agent may be mentioned aliphatic, cycloaliphatic, aromatic, and heterocyclic amines such as m- and p-phenylenediamine, bis(4-aminophenyl)methane, anilineformaldehyde resins, bis(4-aminophenyl) sulphone, ethylenediamine, propane-1,2-diamine, propane-1,3-diamine, N,N-diethylethylenediamine, hexamethylenediamine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, N-(2-hydroxyethyl)-, N-(2-hydroxypropyl)-, and N-(2-cyanoethyl)diethylenetriamine, 2,2,4-trimethylhexane-1,6-diamine, 2,4,4-trimethylhexane-1,6-diamine, m-xylylenediamine, N,N-dimethyl- and N,N-diethylpropane-1,3-diamine, bis(4-aminocyclohexyl)methane, 2,2-bis(4-aminocyclohexyl)propane, 2,2-bis(4-amino-3-methylcyclohexyl)-propane, 3-aminomethyl-3,5,5-trimethylcyclohexylamine (isophoronediamine), and N-(2-aminoethyl)piperazine, and adducts of such polyamines with a stoichiometric deficit of a polyepoxide such as a diglycidyl ether. Suitable polyaminoamides include those prepared from aliphatic polyamines and dimerised or trimerised unsaturated fatty acids. Suitable polycarboxylic acids and their anhydrides include phthalic anhydride, tetrahydro- and hexahydro-phthalic anhydride, methylendomethylenetetrahydrophthalic anhydride, nonenylsuccinic anhydride, dodecenylsuccinic anhydride, hexachloroendomethylenetetrahydrophthalic anhydride and endomethylenetetrahydrophthalic anhydride and their mixtures, maleic anhydride, succinic anhydride, pyromellitic acid dianhydride, benzophenone-3,3',4,4'-tetracarboxylic acid dianhydride, polysebacic anhydride, polyazelaic anhydride, the acids corresponding to the afore-mentioned anhydrides, and also isophthalic acid, terephthalic acid, citric acid, and mellitic acid. Particularly preferred polycarboxylic acid or anhydride curing agents are those which, in admixture if necessary, are liquid at temperatures below 60.degree. C.
The preferred curing agents are polyamines, especially aromatic polyamines.
An effective amount of the curing agent is employed. The proportion will depend on the chemical nature of the curing agent and the properties sought of the curable composition and its cured product; the optimum proportion can readily be determined by methods familiar to those skilled in the art. By way of illustration, however, when the curing agent is an amine there will normally be used from about 0.75 to 1.25 amino-hydrogen equivalents of the amine per 1,2-epoxy equivalent of the epoxide resin. When polycarboxylic acids or their anhydrides are used, usually from about 0.4 to 1.1 carboxylic acid, or carboxylic acid anhydride, equivalents are taken per 1,2-epoxy equivalent.
The amount of the accelerator (b), too, may vary according to such factors as those just mentioned, but usually from 0.2 to 2 parts by weight are employed per 100 parts of the combined weights of the epoxide resin and the curing agent.
The accelerator is best incorporated dissolved in an inert organic solvent such as 2-methoxyethanol, ethylene glycol, diethylene glycol, N-methylpyrrolidone, .gamma.-butyrolactone, benzyl alcohol, dibutyl phthalate, butane-1,4-diol, or ethyl methyl ketone.
Curing can be carried out, depending on the nature of the curing agent, at room temperature (say, 18 to 25.degree. C) or lower (e.g. 0.degree. to 5.degree. C) or at higher temperatures (50.degree. to 180.degree. C, for example).
The new compositions may further contain suitable plasticizers such as dibutyl phthalate, dioctyl phthalate, and tricresyl phosphate, inert diluents such as tars and bitumen and so-called reactive diluents, especially monoepoxides such as n-butyl glycidyl ether, iso-octyl glycidyl ether, phenyl glycidyl ether, cresyl glycidyl ethers, glycidyl esters of tertiary, aliphatic, monocarboxylic acids, glycidyl acrylate, and glycidyl methacrylate. They may also contain additives such as fillers, reinforcing materials, colouring matter, flow control agents, flame inhibitors, and mould lubricants. Suitable extenders, fillers, and reinforcing materials are, for example, glass fibres, carbon fibres, ballotini, mica, quartz flour, calcium carbonate, cellulose, kaolin, wollastonite, colloidal silica having a large specific surface area, powdered poly(vinyl chloride), and powdered polyolefin hydrocarbons such as polyethylene and polypropylene.
The curable compositions of this invention may be used as laminating resins, paints and lacquers, sinter powders, impregnating and casting resins, moulding compositions, putties and sealing compounds, potting and insulating compounds for the electrical industry, and adhesives, and also in the manufacture of such products.
They may be supplied as a two-part pack, one part containing the epoxide resin and the other the curing agent, the accelerator being in either or both parts, but advantageously only in the curing agent part, because some epoxide resins tend to polymerise slowly, over a period of some months, when kept in contact with the halogenated acid or its salts at room temperature.
The following Examples illustrate the invention. Temperatures are in degrees Celsius and, unless otherwise specified, parts are by weight. The accelerating effect is shown, as is conventional in this art, by the reduction in the time taken for the composition to gel, prior to curing; gelation times were determined by means of a "Techne" gelation timer, available from Techne (Cambridge) Ltd., Duxford, Cambridge, England.
The salts were prepared by any of the following methods:
a. The acid was mixed with 10 parts by volume of water and the ammonium, amine, or metal carbonate was added to bring the pH to 7. If the carbonate was insoluble in water, an excess over the theoretical amount was added and, when effervescence ceased, the excess was filtered off.
The resultant solution was evaporated, and the salt was dried, at 100.degree. /13 mm Hg.
b. The amine, ammonium, or metal nitrate was dissolved in ethanol and treated with an equivalent of the barium salt of the acid, also dissolved in ethanol. Barium nitrate precipitated from solution and was filtered off. The solution was evaporated and the product was dried as above.
c. The amine, ammonium, or metal sulphate was dissolved in water and treated with an equivalent of the barium salt of the acid, dissolved in water. Barium sulphate precipitated and was filtered off. The solution was evaporated and the product was dried as above.
"Epoxide resin I" denotes a polyglycidyl ether of 2,2-bis(4-hydroxyphenyl)propane having a 1,2-epoxide content of 5.16 equivalents per kilogram and a viscosity at 21.degree. of 245 poises.
"Epoxide resin II" denotes the diglycidyl ether of butane-1,4-diol.
"Epoxide resin III" denotes N,N'-diglycidyl-5,5-dimethylhydantoin.
"Epoxide resin IV" denotes N-glycidyl-N'-(2-glycidyloxypropyl)-5,5-dimethylhydantoin.
"Epoxide resin V" denotes the tetraglycidyl ether of pentaerythritol, advanced with 2,2-bis(4-hydroxyphenyl)propane to an epoxide content of 8.5 equiv./kg.
"Epoxide resin VI" denotes diglycidyl tetrahydrophthalate; its 1,2-epoxide content was 6.0 equiv./kg.
"Epoxide resin VII" denotes the tetrakis(N-glycidyl) derivative of bis(4-aminophenyl)methane.
"Epoxide resin VIII" denotes 3,4-epoxycyclohexylmethyl 3',4'-epoxycyclohexanecarboxylate.
"Hardener I" denotes a commercially available liquid curing agent, composed essentially of bis(4-aminophenyl)methane.
"Hardener II" denotes triethylenetetramine.
"Hardener III" denotes a 54% solution of bis(4-aminophenyl)methane in .gamma.-butyrolactone.
"HardenerIV" denotes bis(4-amino-3-methylcyclohexyl)methane.
"Hardener V" denotes a polyaminoamide made from dimerised linoleic acid and triethylenetetramine, and is described as Sample 3 of Example 2 in British Patent Specification No. 847028.
"Hardener VI" denotes hexahydrophthalic anhydride.

Polyhalocarboxylic acid salts as accelerators for curing epoxide resins


A shaft bearing system having a housing including a spherical collar for the shaft. The shaft bearing is made up of a cage (19) into which the spherical collar (20) is inserted. The cage is installed in a recess (18) in a housing (16); a sleeve (21) is arranged in the interior of the spherical collar, and an axle stub (22) is inserted into the shaft bearing. The rotational movement preferably takes place between the sleeve (21) and the axle stub (22). The use of the spherical collar in a shaft bearing made up of a cage and a guide bushing has the advantage of greater flexibility in selecting the material or materials from which the housing and the rotatable component installed therein may be formed. The shaft bearing of the invention is particularly useful for accommodating a centrifuge rotor (10) in a centrifuge housing (16).

The invention relates to a shaft bearing comprising a collar with a spherical outer surface for the shaft. For convenience, such a collar will be referred to hereinafter as a spherical collar. Shaft bearings in which spherical collars are used are known. For instance, DE 195 24 953 A1 discloses an electric motor (see FIG. 1), in which the shaft 4 for accommodating the rotor 5 is received in a spherical collar 8 in the housing 7. The spherical collars facilitate compensation of tolerances that, among other things, could also result in an angular displacement of shaft mounted in the bearing. The spherical collar has a cylindrical inner area into which the shaft is inserted, and an outer area that forms a segment of a spherical surface. This may be rotated in an appropriately configured recess in the housing with two rotary degrees of freedom that do not correspond to the degree of freedom of the rotating shaft. This allows any bearing forces that arise to also be minimized even at larger tolerances.
The spherical collars are inserted directly into the housing. In the device according to DE 195 24 953 A1, this is facilitated by elastic latches 32. The shaft 4 is inserted directly in the spherical collar. In such a solution, however, certain guidelines with reference to the materials used for shaft and housing must be observed. If the latches 32 are part of the housing shell, then the housing must be made of an elastic material, particularly plastic. If something more rigid, e.g., metal, is chosen as the material, the recess must be made of several parts in order to receive and rotatably mount the spherical collars 8. For instance, an additional ring with a threaded connection may be provided to form the recess for receiving the spherical collar. However, this would increase the cost of the component, and consequently reduce the economic viability of the bearing.
Furthermore, the direct insertion or mounting of the shaft 4 in the spherical collar 8 necessitates selection of materials with desirable sliding friction properties. This limits the selection of the material pairs. Particularly for shafts made of synthetic resin material (plastic), the life of the structural component is limited by a comparably high frictional wear of the rotating plastic shaft in the spherical collar.
It is an object of the invention to provide a shaft bearing with spherical collar which can be used regardless of the materials chosen for the shaft which is to be bearingly mounted thereby as well as for the recess in which the shaft bearing is installed.
It is also an object of the invention to provide a centrifuge incorporating the shaft bearing of the invention.
These and other objects have been achieved in accordance with the present invention by providing a shaft bearing comprising a spherical collar, in which an outside of the spherical collar is accommodated with two rotational degrees of freedom in a recess; the recess is a part of a cage which forms a pre-assembled unit together with the spherical collar and which can be mounted at a mounting location of the shaft bearing; a rotational body is accommodated in a rotatable manner inside the spherical collar, the rotational body comprising a sleeve into which a component to be rotatably mounted by the shaft bearing can be inserted, and the sleeve is provided with a retaining device which limits the axial play of the sleeve, thereby preventing the sleeve from slipping out of the spherical collar.
In accordance with a further aspect of the invention, the objects are achieved by providing a centrifuge comprising a shaft bearing according to the invention, in which the component to be rotatably mounted by the bearing is a centrifuge rotor, one end of which is received in the shaft bearing.
The shaft bearing according to the invention forms a bearing unit composed of the spherical collar itself and a cage. The spherical collar is arranged in a recess provided in the cage for this purpose. The recess forms the spherical interior surface, which communicates with the corresponding spherical exterior surface of the spherical collar. The cage may be made of a resilient or elastic material, such as plastic. The spherical collar can then be easily pressed into this component without the need for additional fasteners. The shaft bearing can then be simply mounted and fastened at the mounting location, e.g., in a housing. A rotational body, e.g., the shaft to be rotatably mounted in the bearing, then rotates in the interior of the spherical collar.
In accordance with the invention, the rotational body is a sleeve, which is connected to the interior surface of the spherical collar. The component to be rotatably mounted by the bearing is inserted into this sleeve. As a result, a direct connection between the component to be rotatably mounted and the spherical collar is avoided. This facilitates greater flexibility in the selection of the material from which the component to be rotatably mounted, can be made. The relative movement in rotating the component mounted in the bearing takes place between the sleeve and the spherical collar. The component to be rotatably mounted by the bearing is press fitted, adhesively bonded or fastened in some other way in the sleeve. It is thereby determined in accordance with the relative movement of sleeve and spherical collar, which connection exhibits the more favorable gliding properties. In choosing a plastic part to be accommodated, it makes sense, for example, to press this into the sleeve so that the sleeve rotates in the spherical collar. A metal to metal material pairing that exhibits low frictional wear can then be selected for the spherical collar and sleeve, respectively.
In accordance with one advantageous embodiment, two sintered materials are used as a material pairing for the spherical collar and the sleeve. The manufacture of these components of sintered materials results in cost savings because production time is reduced. Moreover, the cost of materials is decreased since sintered parts do not need to be post-treated under tension. Very good surface properties for the spherical collar and sleeve can be attained by producing the parts in a sintering process. This allows for an improvement in the frictional resistance while producing the sliding partner economically. An example of materials for a slide bearing combination with two sintered materials is the use of sintered steel D11 and sintered bronze B50, respectively, for the two sliding parts.
In accordance with another advantageous embodiment of the invention, an arresting element may be provided between the cage and the mounting location to secure the shaft bearing. This arresting element enables the shaft bearing to be secured in the mounting location without placing the shaft bearing under stress. This can be achieved through use of an interlocking connection. It is also possible to provide latching elements on the cage. These latching elements, particularly when made of plastic, may be elastically deformed when pushed into the mounting location, and then rebound into mating receptacles in the mounting recess, so that the cage is mounted in position without being under stress. A further possibility is to provide stud screw, which is arranged in a thread at the mounting location, and which when screwed in, secures the cage in the mounting location without placing it under stress. An appropriate projecting part can be provided in the cage for engaging the screw. In comparison with pressing fitting the shaft bearing in its mounting location, the provision of an interlocking arresting element which does not stress the bearing has the advantage that the bearing parts will not be deformed in such a way that the spherical collar will move stiffly in the cage. In this way, the function of the spherical collar, which is to compensate for an offset angle of the rotational body, is unlimited.
If the sleeve is accommodated in the spherical collar in a rotatable manner, then in accordance with one advantageous embodiment of the invention, it can be provided with a retaining device. This may comprise a shoulder, for example, which prevents the sleeve from slipping out of the spherical collar. This reduces the probability of error when mounting or replacing the component to be rotatably mounted in the bearing. By selecting an appropriate sleeve length and providing clearance in the receiving cage, the sleeve can be provided with axial play despite the presence of the retaining device. This gives the shaft bearing a further, axial degree of freedom, which allows the shaft bearing to be used as a movable bearing.
The shaft bearing according to the invention is suitable for installation in a centrifuge, in which the component to be rotatably mounted by the bearing is a centrifuge rotor. Such a rotor can be equipped at least on one end with a shaft bearing according to the invention. This brings with it the aforementioned advantages, especially in conjunction with a centrifugal rotor produced of synthetic resin material.
Since centrifugal rotors are operated with high rotational speed, it is particularly advantageous that the bearing can be secured in its mounting position without placing it under stress which might distort one or more of the bearing parts and impede its free rotation. The occurrence of angle tolerances with respect to the rotational axis of the rotor does not limit its functionality. This measure also reduces the component stress acting on the rotor. Not least, this may minimize the occurrence of balance errors in the centrifugal rotor during its service life.
In one advantageous embodiment of the centrifuge, the rotor support axle to be received in the shaft bearing is constructed as a hollow shaft. At the same time, a supply opening is provided in the cage of the shaft bearing. This results in an inlet channel for a fluid to be centrifuged. This fluid enters the cage through the supply opening and is conducted through the hollow shaft into the interior space of the centrifugal rotor. If the centrifuge is operated as an oil centrifuge, this structural configuration simultaneously achieves a reliable lubrication of the spherical collar, thereby minimizing its frictional wear. Insofar as play is provided between the spherical collar and the cage, a seal is generated here because of the applied oil pressure, since the oil pressure presses the spherical collar in its recess, in a manner similar to a ball valve.
In the described case of a centrifuge, it is therefore necessary that the individual components of the shaft bearing, comprising the cage, the spherical collar, and the sleeve, can be sealed relative to one another. This is achieved through appropriate surface pairings. Moreover, the cage must be sealed relative to the mounting location, and the sleeve must be sealed relative to the rotational body. Here, a slight leakage flow may be acceptable, however, depending on the application. It is possible to use a sealed shaft bearing of the aforedescribed type wherever the shaft bearing is installed in a boundary region between a fluid-conducting space and a space sealed from this fluid. This is particularly the case when a fluid is to be simultaneously passed through the shaft bearing, e.g., through the component which is to rotatably mounted by the bearing.
These and other features of preferred embodiments of the invention, in addition to being set forth in the claims, are also disclosed in the specification and/or the drawings, and the individual features each may be implemented in embodiments of the invention either individually or in the form of subcombinations of two or more features and can be applied to other fields of use and may constitute advantageous, separately protectable constructions for which protection is also claimed.

Shaft bearing with spherical collar for the shaft