An aqueous composition for the reduction or elimination of unpleasant odors from surfaces containing such odors comprises a perfume, a surfactant/solubilizer, a solvent/drying aid, an odor absorber, and, preferably, a buffer to maintain the desired pH. The solution contains minimal or no volatile organic compounds. Due to the specific nature of the combination of the surfactant/solubilizer and the solvent/drying aid, the use of fragrances previously too hydrophobic for use in an aqueous solution is possible, providing a large variety of efficient odor counteractants not previously available. The composition may optionally comprise additional components, such as preservatives, antimicrobials, anti-static compositions, anti-wrinkling agents, insect control agents, moth repellents, UV protectants, water-proofing agents, and textile treatment agents. The aqueous solution may be applied to a variety of surfaces, in sufficient quantity to wet the surface, preferably by spraying.

Not applicable.
Not applicable.
The present invention relates to aqueous compositions for reduction of objectionable odors from surfaces, comprising water, an odor absorber or odor in counteractant, perfume, solvent, solubilizer, and drying aid. The composition is designed to reduce the presence of objectionable odors, such as food odors, tobacco odors, perspiration, etc., on surfaces such as clothing or fabric such as on furniture. The compositions of the present invention are fast drying, and leave little or no residue on the surface after drying. While specifically designed for use with soft surfaces, such as fabrics, the compositions of the present invention may also be used on hard surfaces, such as garbage and refuse containers and recycling bins, or on such surfaces as appliances, counters, floors, cabinets, walls, and plumbing fixtures in kitchens and bath rooms.
The present invention relates to an aqueous composition suitable for use as a freshening composition. Such a composition may be sprayed onto fabrics, particularly clothing, to restore the freshness thereof by elimination or reduction of malodors, between washings or dry cleanings. The composition may also be sprayed upon fabric covered furniture, or other surfaces, to eliminate malodors, such as pet odors, or tobacco odor, without deposition of a residue upon the surface.
A wide variety of deodorizing compositions are known, most commonly containing a perfume to mask or hide the malodor. Odor masking is the intentional concealment of one odor by over-powering it with another, preferably more acceptable odor, such as a fragrance. The masking perfumes used vary greatly, dependent upon application, such as masking perspiration odor, bathroom odor, pet odors, tobacco, etc. The appropriate fragrance for a given composition needs to be selected in accordance with the end product usage, as well as the goal to give the impression of freshness.
Odor modification, i.e. changing the odor by chemical modification, has also been used. Such techniques include oxidative degradation, which uses oxidizing agents such as oxygen bleaches, chlorine, sodium hypochlorite, or similar materials. In addition, reductive degradation has been attempted, using reducing agents such as sodium bisulfite to reduce malodor. However, both of these techniques are unacceptable due to damage they cause to fabrics, especially colored fabrics.
Other odor control methods employ actives which react with malodors having specific functional groups, such as biguanide polymers, which complex with organically bound nitrogen and/or sulfur atoms, or fatty alcohol esters of methyl methacrylic acid, which react with thiols, amine, and aldehydes. Such reactive materials, however, are generally not water soluble.
In addition, antibacterial and antifungal agents which regulate the odor producing microorganisms found on surfaces, have been employed, but are ineffective on malodors not caused by bacterial sources.
The present invention is most specifically directed at environmental odors, such as tobacco odor, cooking and food odors, and body odor. These odors are generally organic in nature, and frequently result from low molecular weight, straight-chain, branched, and unsaturated C6-C11 fatty acids.
U.S. Pat. No. 5,670,475, of Trinh et al is one of a number of patents related to the concept of reducing xe2x80x9cmalodor impressionxe2x80x9d from surfaces. Other relevant Trinh et al patents include U.S. Pat. Nos. 5,578,563; 5,633,134; 5,783,544; 5,968,404; 5,939,060; and 6,077,318. U.S. Pat. No. 5,670,475 teaches aqueous deodorizing compositions comprising up to about 1% perfume, and preferably including water-soluble cyclodextrins, water-soluble metal salts, and solubilizing aids. Cyclodextrins function in a manner similar to molecular sieves, which are also employed to entrap perfumes, odors, etc., and which may also be employed for removal of malodor from surfaces. Exemplary metal salts include zinc salts such as zinc sulfate, and exemplary solubilizers include ethoxylated aliphatic alcohols. In the preferred embodiments of the patent, the perfumes used in the compositions are those having a C log P of less than 3, it being indicated that such perfumes may be solubilized in water without the use of a solubilizing alcohol, whereas those perfumes with a C log P value greater than about 3 are less useful due to greater hydrophobicity. The patentee indicates that the composition contains less than about 5% low molecular weight monohydric alcohol. Cyclodextrin molecules are known to form complexes with perfume ingredients, and have been used as perfume carriers in the past. Trinh et al teach that fabrics treated with cyclodextrin exhibit perfume release upon rewetting, resulting in an impression of freshness of the fabric when said fabric is rewetted.
However, the prior art compositions are subject to slow rates of drying, and deposition of residues on the substrates treated. It is also to be noted that the Trinh et al reference specifically suggests that the perfumes used be those having a C log P value of 3 or less, to require the use of predominant proportions of those perfumes which are most hydrophilic or water soluble. This limitation prevents the utilization of a large number of popular and effective scents useful for the purpose of reducing malodor impression.
However, it is also to be noted that the presence of volatile organic compounds, or VOCs, such as alcohols, is not desirable, even though they are very effective solubilizers for perfumes, and impart rapid dry time to a surface treatment system. Such solvents are often odor objectionable in themselves, as well as being environmentally undesirable. Accordingly, it is an object of the present invention to provide a water-based deodorizing composition for treatment of surfaces, said composition preferably not containing objectionable VOCs, while still permitting the use of hydrophobic fragrances.
In one aspect, the invention is directed to a water-based deodorizing composition for the treatment of surfaces, the composition having a good dry time without use of volatile ingredients such as alcohols, and leaving little or no residue on the surface treated. The invention also relates to methods for using this composition for deodorizing surfaces such as fabrics and clothing.
In yet another form, the invention provides a low residue treatment for the removal of odors on surfaces, using a composition containing fragrances with a C log P value greater than about 3. The composition of the present invention further removes odors without damage to surfaces, and has an acceptable dry time without the addition of VOCs.
The compositions of this invention may be applied to any surface which would not be damaged, objectionably spotted, or otherwise compromised by the application of an aqueous spray, if that surface is subject to malodor retention. For example, one would not spray a rice paper screen with an aqueous composition of the present invention, but one may use said composition on the surface of a cloth or wooden screen, or a leather or fabric car seat. The present compositions are not intended as cleansing agents, such as may be used to clean a hard surface such as a glass table, mirror, kitchen counter, toilet, or trash receptacle, but such compositions may be sprayed upon such surfaces if they have become odorous. In such cases, the surface should first be cleaned in a conventional manner, and then the composition should be sprayed upon the cleaned surface and allowed to dry without wiping, to minimize streaking or clouding of the surface, particularly of shiny surfaces, while providing maximum deodorizing effect. As indicated, the compositions of this invention are primarily intended for use on soft surfaces, such as clothing, shoes, carpeting, upholstery, curtains, draperies, linens, etc., but are not limited to such surfaces. These compositions, by virtue of the fact that they leave little or no residue upon drying, and are non-staining, non-toxic and non-injurious to most surfaces when used as intended, may be used upon almost any surface which may be contacted with an aqueous spray, such as kitchen and bath counters, appliances, and fixtures, floors, walls, and containers such as garbage cans, storage bins, etc., which are subject to malodor retention from materials with which they come in contact, or from air borne malodors such as smoke and tobacco odors.
Preferred embodiments of the invention contain a solvent to surfactant ratio of approximately 2:1, and a fragrance to surfactant ratio of 1:3. The compositions taught also exhibit a preferred skin compatible pH range of from 5 to 6, although a pH range of from about 3 to about 7 is acceptable. More-over, the composition may be incorporated into a spray dispenser to create a consumer product which may be readily used in the home or elsewhere to reduce or eliminate objectionable odors upon a surface without leaving a stain or residue.
Thus, a primary object of the invention is to provide an aqueous composition which may be applied, preferably but not necessarily as a spray, to a surface to lessen or eliminate the presence of malodors in or on said surface. Another object is to provide a means for removal of objectionable odors from fabrics, such as clothing, without staining the fabric or leaving an objectionable residue thereupon, preferably without the use of compositions containing objectionable VOCs.
The objects of the present invention therefore include providing a fragranced is aqueous composition comprising, for example, a butyl ether solvent and drying aid, a primary alcohol ethoxylate solvent or solubilizer for the fragrance, a metal salt odor absorber, pH adjustment means, and a preservative.
These and still other objects and advantages of the present invention (e.g. methods for using such compositions) will be apparent from the description which follows, which description is merely of the preferred embodiments. Thus, the claims should be looked to in order to understand the full scope of the invention.
Aqueous solutions of active ingredients are used in the present invention for the treatment of surfaces to eliminate or reduce odors. The preferred carrier is accordingly water, per se, which may be softened, distilled, deionized, or tap water, and which is relatively pure, containing no material which will leave a residue or stain upon surfaces, such as fabric, upon which the solution is sprayed and allowed to dry. The water also should preferably contain little or no low molecular weight alcohol, or other VOCs. Such materials may be present in limited amounts due to their presence in some perfumes, preservatives, and/or stabilizers, but it is preferred that the level of such VOCs be limited to less than about 1 percent, and preferably less than about 0.25 percent.
The present invention thus relates to an aqueous composition for reduction of objectionable odors from surfaces, said composition comprising water, odor absorber, fragrance, a surfactant/solubilizer, and a solvent/drying aid. More specifically, the composition comprises from about 0.01 to about 1.0 weight percent of a fragrance or perfume, said perfume being any perfume which exhibits water solubility sufficient, in the presence of a solubilizer therefor, for the purpose of the invention. Such perfumes are a matter of individual taste and preference, and may be varied to satisfy the preferences of differing markets internationally, or to complement or counter the specific malodor being attacked.
The perfumes suitable for use in the present invention are those which have odor characteristics acceptable for the purpose of reducing or eliminating the impression of unacceptable odors, primarily by masking such unacceptable odors. Whereas in the past, the fragrance materials used for such purpose were limited by their hydrophobic nature, applicant has now determined that many previously unsuitable fragrances may be used in the aqueous solutions of the present invention, but only if utilized with specific surfactant/solubilizers as set forth herein. For example, the perfumes suitable for use in the present invention include such perfumes as are commonly referred to as fresh clean, spicy, floral, citrus, ozone, and marine types. Preferred perfumes are selected from those referred to as fresh clean, and floral types. Preferably, the treatment solution of the present invention contains an effective amount of perfume to provide a freshening fragrance to surfaces upon first application, and some lingering fragrance during wear, and after drying to the touch. Effective levels of perfume are from about 0.01 percent to about 1.0 percent, preferably from about 0.01 percent to about 0.5 percent, and most preferably from about 0.015 percent to about 0.3 percent by weight.
To achieve the utilization of many more desirable fragrances in the present invention, it is necessary to provide for their solubilization in the water base of the composition. It has now been found that fragrances with a C log P value of greater than 3 may be utilized in the present invention, whereas previous attempts to utilize such fragrances have been unsuccessful. The term C log P as used herein refers to the degree of hydrophobicity of a perfume ingredient, correlated with the octanol/water partitioning coefficient thereof, P. Higher P values are more hydrophobic, and since the partitioning coefficients are normally high values, they are conventionally ally referred to in the form of their logarithm to the base 10, or log P. The log P values of many perfume ingredients are readily available from such sources as the Pomona 92 database, available from Daylight Chemical Information Systems, Inc. (Daylight CIS), Irvine, Calif. However, the log P values are most conveniently calculated by the use of the xe2x80x9cC log Pxe2x80x9d program, also available from Daylight CIS. The xe2x80x9ccalculated log Pxe2x80x9d (C log P) is based upon the fragment approach of Hansch and Leo (A. Leo, in Comprehensive Medicinal Chemistry, Vol. 4, C. Hansch, P. G. Sammens, J. B. Taylor, and C. A. Ramsden, Eds., p.295, Pergamon Press, 1990, incorporated herein by reference). The C log P values are considered the most reliable and widely used estimates for this important property, and are used instead of experimental log P values in evaluation of hydrophobicity of fragrance ingredients.
It has now been found that such fragrances may be utilized in the presence of a specific surfactant, or a combination of surfactants of the same or differing classes of surfactants, which act as a solubilizer for fragrances having a C log P value greater than about 3, in combination with a specific class of compounds normally referred to as solvents, but which in the present application act as a wetting agent and drying aid. Accordingly, the term surfactant/solubilizer, as used hereinafter, shall be meant to refer to individual surfactants, combinations of surfactants from the same class (ionic, non-ionic, cationic, or amphoteric), and combinations of surfactants from different classes, which have the ability to solubilize perfumes having a C log P higher than about 3. Suitable surfactant/solubilizers for the present invention have been found to include such surfactants as C9-11 linear primary alcohol ethoxylates. Other suitable surfactant/solubilizers for use in the present invention include such non-ionics as ethoxylated fatty alcohols, C9-11 linear primary alcohols, polyoxyethylene oleyl ethers, and alkoxylated biodegradable hydrotropes; such anionics as ether sulfates and linear ethylene oxide; selected cationics such as quatemary ammonium halides; and selected amphoterics including betaines such as capryloamidopropyl betaine. Thus, the surfactant/solubilizer may preferably be selected from the group consisting of linear primary alcohols, ethoxylated fatty alcohols, linear primary alcohol ethoxylates, polyoxyethylene ethers, alkoxylated biodegradable hydrotropes, linear ethylene oxide, quatemary ammonium halides, betaines, amine oxides, and mixtures thereof. Such surfactant/solubilizers may be used individually or in combination, based upon the solubility parameters of the fragrance to be employed, and may be present in concentrations of from about 0.1 to about 10.0 weight percent and preferably from about 0.5 to 5 weight percent. In the most preferred embodiments of the invention, a C9-11 linear primary alcohol ethoxylate surfactant was employed in a concentration of from 1 to 2 percent by weight.
However, it has been found that when a sufficient quantity of the surfactant/solubilizer is employed to ensure dissolution of the fragrance oil, the surfactant/solubilizer frequently leaves a residue, or stain, upon drying. Accordingly, it is desirable to employ an additional solvent material to aid in solubilizing the fragrance, and to help to wet the fabric to which the solution is applied. Since this solvent also acts to enhance drying of the solution, it shall be referred to hereinafter as a solvent/drying aid. Suitable compositions for this purpose include certain water soluble non-VOC solvents, such as butyl carbitol, a diethylene glycol butyl ether. It has been found that both carbitol and butyl carbitol are suitable, and that while butyl carbitol may be preferable for environmental reasons, mixtures of both may be particularly useful. Such solvent drying aids include such compounds as glycol ethers such as ethylene glycol butyl ether, tri(propylene glycol)methyl ether, 1-methoxy-2-propanol, diethylene glycol monoethyl ether, and glycol ether acetates such as propylene glycol methyl ether acetate, and may be present in concentrations of from about 0.05 to about 20 weight percent. In a preferred embodiment of the invention, butyl carbitol was present in a concentration of 4.5 weight percent. Preferred ranges for the solvent/drying aids may range from 1 to about 10 weight percent, more preferably from about 3 to 6 weight percent of the composition, and most preferably from about 4 to 5 weight percent of the composition.
In addition, from about 0.05 to about 5.0 weight percent of an odor absorbing metal salt should be present, selected from the group consisting of water soluble salts of metals such as zinc, copper, silver, zirconium, nickel, chromium and other transition metals. Such salts may include those acetates, chlorides, sulfates, nitrates, gluconates, maleates, lactates, salicylates, and other salts as are water soluble and have odor absorption characteristics. Thus, suitable odor control agents may comprise from 0.05 to about 5.0 weight percent, and preferably from about 0.075 to about 0.2 weight percent (based upon the total weight of the composition) of a water soluble salt selected from the group consisting of the acetates, chlorides, sulfates, nitrates, gluconates, maleates, lactates, and salicylates of zinc, copper, silver, titanium, zirconium, nickel, chromium, and other transition metals.
In addition to the above, it has been found highly beneficial to include in the composition a pH buffering agent, preferably sodium citrate, which may be used in combination with a buffering acid to combat pH drift which occurs upon heating of an aqueous solution of the above noted components. The purpose of a buffering agent is to permit a solution to resist changes in concentration of H+ ions in solution, due to either internal or external influences, such as heating, which may be encountered during storage and shipment of commercial product. Buffers are conventionally composed of weak acids and bases, which do not completely ionize in solution. A combination of sodium citrate and citric acid is the preferred buffering agent for the present invention, due to the presence of three carbonyl groups, resulting in three different pKa values. Metal salt odor control agents, such as zinc salts, are difficult to stabilize, since zinc ions, for example, tend to form insoluble salts in solution, which may result in a shift in pH, which may result in discoloration or corrosion. Accordingly, it was desired that a buffer system with a pKa value within 1 unit of the desired pH range of 4.5 to 5.5 be selected. It was found that the combination of sodium citrate with citric acid controlled the pH, by serving as a ligand and complexing with the metal from the odor controlling metal salt, to form a chelate which tied up the chemical reactivity, but not the odor complexing capabilities of the metal ions. The target pH for the present invention is in the range of from about 4.5 to about 5.5, while the effective pKa values for citric acid in such a solution are from about 4.7 to about 5.4, creating an effective system to control the formula pH in the target range. While sodium citrate is the preferred citrate, other citrates, such as potassium citrate, are also suitable. Other acids in the appropriate pKa range may also be used in place of citric acid, such as succinic and acetic acids. Appropriate amounts of buffering agent, comprising a citrate salt in combination with a buffering acid, should be added to achieve the desired pH. Buffering acid may be added in addition, to arrive at the appropriate target pH range. It is also to be noted that a buffering acid may not be required if the surfactant itself is acidic and can thus serve as an ion donor.
Still further, optional components may be included, such as from 0 to about 1.0 weight percent of a preservative or stabilizer; from 0 to about 10.0 weight percent of a moth or insect repellant; from 0 to about 10 weight percent anti-static compound; from 0 to about 5 weight percent of an antimicrobial compound; and from 0 to about 0.5 weight percent of a coloring agent. Other suitable optional components may be added, as will be apparent to those skilled in the art, without detracting from the efficacy of the presently set forth compositions, and such shall be considered within the scope of the present invention.
As indicated, a preservative may also be present, although not required for the purpose of the present invention. Suitable preservatives are well known in the art, and include such compositions as Kathon(copyright) CG, a 5-Chloro-2-methyl-4-isothiazolin-3one compound available from Rohm and Haas. The concentration of preservative should be sufficient to perform the function for which it is added, and may be, for example, 0.05 weight percent of the composition. The preservative may be any organic preservative material which will not cause damage to the surfaces to which the solutions are to be applied, such as discoloration, coloration, or bleaching. Preferred water soluble preservatives include organic sulfur compounds, halogenated compounds, cyclic organic nitrogen compounds, low molecular weight aldehydes, quaternary compounds, dihydroacetic acid, phenyl and phenoxy compounds, and mixtures thereof.
In addition, antimicrobial or antibacterial compositions may also be present, although not required in the present invention. Suitable compounds for this purpose include such compounds as Myristalkonium chloride and Quatemium 14. Other well known water soluble antimicrobial agents may be used, such as Benzylkonium chloride, zinc gluconate, anti-microbial anionic surfactants, and quatemary amphoteric surfactants.
Still further, other compositions may be present for specific purposes, such as anti-static, and anti-wrinkling additives. Suitable compositions for these purposes include monoalkyl cationic quatemary ammonium compounds, polyethylene glycols, polymeric quaternary ammonium salts, quaternized polyethyleneimines, etc, Other textile treatment agents like water-proofing, flame retardants, UV protectants or stain repellents may also be appropriate.
Insect control or moth repelling agents may also be optionally included, such as pheromones, citronellol, citranellal, citral, linalool, etc. Many such compositions are known in the art, and the specific agents employed are a matter of choice, dependent upon the specific need of the consumer.
The aqueous solutions of the present invention may be utilized in a variety of ways. The most commonly employed method for application of malodor counteractants is to spray the composition on the surface of the fabric, clothing, furniture, or other object which is subject to the presence of the unpleasant odor, spraying sufficient solution to slightly dampen the surface. This is most easily accomplished by means of a spray bottle, comprising a container, most favorably a light weight flexible plastic, and a spray nozzle means by which the liquid may be forced, under pressure provided by either a pump mechanism or by pressurization of the container. Such a spray application of the solution of the present invention is accordingly considered within the scope of the invention, as is the means thereof including both liquid spray, as above, and aerosol application. In addition, it is possible that the solution of the present invention may be applied by alternative means, such as by addition to a rinse cycle during laundering or dry-cleaning, or by direct application of the liquid solution to the surface by pouring, rubbing with a liquid containing absorbent material, etc. Preferably, the amount of solution applied need not saturate or cause a pooling of liquid on the article or surface, but should be sufficient to achieve the elimination or decrease of malodor without leaving a readily discernible visible deposit after drying.


A composition for improving isoflavone metabolism and the bioavailability of phytoestrogens in warm blooded animals comprising a phytoestrogen, a dietary fiber, L-glutamine, and optionally N-acetyl-D-glucosamine, in admixture with a biologically acceptable inert carrier.

This invention relates to nutritional supplements. More particularly, the invention relates to a nutritional supplement composition, and methods of use thereof, to enhance the bioavailability of isoflavone.
Nearly 70 years ago, it was reported that certain plants could induce estrus in animals. Subsequently, over 300 plants have been found to possess estrogenic activity (see e.g., Bradbury and White, Vitamin Horm. 12:207 (1954), and Farnsworth et al., J. Pharm. Sci. 64:717(1954)). These compounds have been given the general name of xe2x80x9cphytoestrogensxe2x80x9d and represent several chemical classes of diphenolic plant compounds that are somewhat related structurally to the mammalian sex hormone 17-beta-estradiol. See Setchell, K. D. R., et al Am. J. Clin. Nutr., 40:569 to 578 (1984). Similarities in the molecular structure of phytoestrogens facilitate binding to the estrogen receptor. An important class of the phytoestrogens is the isoflavone class. Two chemical classes of phytoestrogens are abundant in soybeans, total soy products, and soy protein isolates. Those two classes are coumestrol and isoflavones. The latter class includes daidzein, genistein, glycitein, as well as their glycoside and acetylated forms.
Phytoestrogens and their metabolites interact with specific cell receptors and compete with endogenous hormone molecules [see Folman, Y. et al, J. Endocr., 44:213 to 218 (1969)], but the biological estrogen-like effect of these compounds is relatively weak. See Kaziro, R. et al, J. Endocr., 103:395 to 399 (1984) and Tang, B. Y. et al, J. Endocr. 85:291 to 297 (1980). Phytoestrogens can induce two different effects in an organism. When the level of endogenous sex hormones is relatively high, the antiestrogenic effect prevails. There are several mechanisms of antiestrogenic activity of the phytoestrogens, including feedback inhibition at the hypothalamus and pituitary gland, and competition and blockade of cell receptors. It has been observed that a phytoestrogen and lignan-rich diet is associated with a reduction in free plasma estradiol, and in reduction of the risk of breast cancer. See Adlercreutz, H. et al, J. Steroid. Biochem., 27:1135 to 1144 (1987) and Mousavi, Y. et al, Steroids, 58:301 to 304 (1993). On the other hand, in postmenopausal women, phytoestrogens can provoke an estrogenic response. See Adlercruetz, H. et al, Lancet, 339:1233 (1992). This dual effect of weak estrogens is demonstrated, and well known xe2x80x9cpartialxe2x80x9d antigens such as Tamoxifen have these properties.
Phytoestrogens have been demonstrated in clinical trials to modulate the menstrual cycle, reduce menopausal symptoms, and lower LDL cholesterol levels. J. Nutr., 1996, 126(1): 161-7; N. Engl. J. Med., 1995, 333: 276-82. Epidemiologic observations indicate women in countries where diets are rich in phytoestrogens (averaging about 40-50 mg/day) have a decreased incidence of breast cancer, menopausal symptoms and osteoporosis. Nutr. Cancer, 1994,21:113-131; J. Nutr., 1995,125; 757S--770S; Am. J. Clin. Nutr. 1995,62:645. Animal studies have provided a biological basis for these observations. J. Ster. Biochem and Mol. Bio., 1992, 41(3-8): 331-7; First International Symposium on the role of Soy and Preventing and Treating Chronic Disease (1994), Speaker Abstracts.
Soybeans are a particularly important source of phytoestrogens. Several hundred varieties or cultivars of soybeans exist, and their phytoestrogen content can vary from 50 mg/100 g to 300 mg/100 g. In addition, given the high levels of consumption of soy protein by certain Oriental cultures, there is a substantial body of relevant epidemiologic evidence. For example, there is epidemiologic evidence that phytoestrogens are associated with a lower risk of development of breast and uterine cancer. Experimental evidence for lower breast cancer incidence associated with dietary intake of phytoestrogens in soybeans has also been reported (Barnes et al., In Jacobs M M, ed., Diet and Cancer: Markers, prevention and treatment, New York: Plenum Press, 135 (1994)). Specifically, dietary soy protein preparations enriched with phytoestrogens inhibited mammary tumors in rats treated with 7,12-dimethyl-benz[a]anthracene compared to rats fed low-phytoestrogen soy protein preparations.
The increasingly frequent suggestion that phytoestrogens may protect against development of coronary artery atherosclerosis (CAA) and coronary heart disease(CHD) is based on the evidence that endogenous estrogen protects premenopausal women from CHD relative to men of the same age, that loss of ovarian hormones accounts for the increase in CHD in postmenopausal women, and that estrogen replacement decreases CHD risk among postmenopausal women.
In addition to the epidemiological evidence, recent experimental observations have suggested that phytoestrogens may protect against the development of CAA. For example, studies have shown that male casein-fed rats had significantly higher total plasma cholesterol (TPC) and low density lipoprotein cholesterol (LDL-C) concentrations than soy protein-fed rats. When soybean phytoestrogens were added to casein, the animals had LDL-C concentrations similar to the soy protein-fed group.
It has been recently recognized that the isoflavones contained in vegetable proteins, such as soybeans, may inhibit the growth of human cancer cells, such as breast cancer cells and prostrate cancer cells, and is described in the following articles: xe2x80x9cGenistein Inhibition of the Growth of Human Breast Cancer Cells; xe2x80x9cIndependence from Estrogen Receptors and the Multi-Drug Resistance Genexe2x80x9d by Peterson and Barnes Biochemical and Biophysical Research, Communications; Vol. 179, No. 1, pp. 661-667, Aug. 30, 1992; xe2x80x9cGenistein and Biochanin A Inhibit the Growth of Human Prostate Cancer Cells but not Epidermal Growth Factor Receptor Tyrosine Auto-phosphorylationxe2x80x9d by Peterson and Barnes: The Prostate 22: pp. 335-345 (1993) and xe2x80x9cSoybeans Inhibit Mammary Tumors in Models of Breast Cancerxe2x80x9d by Barnes, et al. Mutagens and Carcinogens in the Diet; p. 239-253 (1990).
Isoflavones have been added to nutritional supplements for a variety of therapeutic purposes as shown in U.S. Pat. Nos. 5,523,087; 5,424,331; 5,516,528 and 5,807,586. The bioavailability in human subjects of dietary isoflavones is of great importance relative to their biofunctional effects. Once ingested, several factors influence the bioavailability of isoflavones. Simply adding phytoestrogen-rich foods to the diet may not ensure effective bioavailability because isoflavones cannot work unless they are first converted to biologically active estrogen-like compounds by friendly intestinal bacteria. Since the presence of friendly bacteria is, in turn, dependent upon a healthy gastrointestinal climate, all the dietary and lifestyle factors that affect the digestive tract can have significant impact on the bioavailability of dietary isoflavones.
In view of the foregoing, there is a need for a composition for the enhancement of isoflavone bioavailability in human beings and other warm blooded animals that improves digestive tract environment.
The present invention provides a composition and a method for improving the gastrointestinal climate for beneficial microorganism growth in warm blooded animals.
The present invention also provides a composition and a method for improving isoflavone metabolism and the bioavailability of phytoestrogens in warm blooded animals.
One embodiment of the present invention is a dietary supplement composition for administration to warm blooded animals comprising a fiber, L-glutamine and a phytoestrogen.
Another embodiment of the present invention is a method for improving the gastrointestinal climate for friendly bacterial growth and the bioavailability of phytoestrogen comprising the steps of administering effective amounts of a composition comprising fiber, L-glutamine and a phytoestrogen.
Before the present composition and methods of making and using thereof are disclosed and described, it is to be understood that this invention is not limited to the particular configurations, process steps, and materials disclosed herein as such configurations, process steps, and materials may vary somewhat. It is also to be understood that the terminology employed herein is used for the purpose of describing particular embodiments only and is not intended to be limiting since the scope of the present invention will be limited only by the appended claims and equivalents thereof.
It must be noted that, as used in this specification and the appended claims, the singular forms xe2x80x9ca,xe2x80x9d xe2x80x9can,xe2x80x9d and xe2x80x9cthexe2x80x9d include plural referents unless the context clearly dictates otherwise.
Herein there is described a composition and a method of use thereof to improve the gastrointestinal climate for friendly bacterial growth in warm blooded animals and to enhance the bioavailability of phytoestrogens, which comprises the step of administering effective amounts of a composition comprising a fiber, L-glutamine, and a phytoestrogen. Improvement of the gastrointestinal climate for friendly bacterial enhances beneficial bacteria growth, which in turn enhances the metabolism and bioavailability of phytoestrogens, such as isoflavones.
As used herein, xe2x80x9csubjectxe2x80x9d refers to any mammal, including humans. The methods herein for use on subjects contemplate prophylactic use as well as curative use as part of therapy for an existing condition.
The term xe2x80x9cphytoestrogenxe2x80x9d as used herein represents several chemical classes of diphenolic plant compounds that are somewhat related structurally to the mammalian sex hormone, 17-xcex2-estradiol. Two chemical classes of phytoestrogens are abundant in soybeans, total soy products, and soy protein isolates. Those two classes are coumestrol and isoflavones. The isoflavone class includes daidzein, genistein, glycitein, as well as their glycoside and acetylated forms. Therefore, when the present invention refers to enhancement of the bioavailability of isoflavones, it means phytoestrogen isoflavones including daidzein, genistein, glycitein, as well as their glycoside and acetylated forms and other functional derivatives, which are all within the scope of the present invention.
The term xe2x80x9cprobiotic microorganismxe2x80x9d or xe2x80x9cfriendly bacteriaxe2x80x9d as used herein represents microorganisms and bacteria in the gastrointestinal tract which help absorption and metabolism of phytoestrogens and so are beneficial to the host. There are three main kinds of beneficial bacteria, i.e. Bifidobacterium, Lactobacillus acidophilus and Lactobacillus bulgaricus.
The definition of the term xe2x80x9cfiberxe2x80x9d and xe2x80x9cdietary fiberxe2x80x9d as used herein includes unavailable carbohydrates, indigestible residue, and plant cell polysaccharides and lignin, all of which are resistant to hydrolysis by human digestive enzymes. Preferred fibers are members selected from the group consisting of guar gum, pectin, fructo-oligosaccharides and derivatives thereof. Small amounts of other indigestible compounds, such as phytates, tannins, saponins and cutin, may be included in dietary fiber since these compounds are indigestible and associated with dietary fiber polysaccharides.
As used herein, xe2x80x9ceffective amountxe2x80x9d means an amount of the component of the composition of the present invention sufficient to provide the selected local or systemic effect and performance at a reasonable benefit/risk ratio that would attend any acceptable medical treatment.
As used herein, xe2x80x9cadministeringxe2x80x9d, and similar terms mean delivering the multi-nutritional supplemental composition, according to the present invention, to the subject being treated such that the composition is capable of being circulated systemically to the parts of the body where the composition can contact the target cells. Thus, the composition is preferably orally administered to the individual.
The invention, in one of its most general embodiments, concerns a composition and a method of use thereof to enhance the bioavailability of phytoestrogens by improving the gastrointestinal climate for friendly bacterial growth. The composition comprises a fiber, L-glutamine and a phytoestrogen. Preferably, a daily dosage form of the composition will comprise 100 mg to 20 gms of fiber, 25 mg to 10 gms of L-glutamine, 25 to 1000 mg of phytoestrogen, and optionally, 25 mg to 1000 mg of N-acetyl-D-glucosamine. More preferably, a daily dosage form of the composition will comprise 80 mg to 15 gms of fiber, 20 mg to 5 gms of L-glutamine,20 to 1000 mg of phytoestrogen, and optionally, 25 mg to 100 mg of N-acetyl-D-glucosamine. The weight ratio of the phtoestrogen, the dietary fiber and the L-glutamine is within a range of about 1:4:1 to 1:20:10, and preferably within a range of 1:4:1 to 1:15:5. The daily dosage form may be formulated as a single dosage or as multiple dosages which be administered at time intervals throughout the day.
There are two classes of phytoestrogens, isoflavones and coumestans, that are especially contemplated to be within the scope of the present invention. Examples of the isoflavones include daidzein, genistein, glycitein, and their glycosides: daidzin, genistin, and glycitin, as well as acetylated forms of the above mentioned compounds. An example of a coumestan is coumestrol.
In plants, isoflavones are inactive when present in the bound form as glycosides, but when the sugar residue is removed, these compounds become activated. These plant compounds undergo fermentation by intestinal microflora, with both metabolites and unfermented parent (aglycone) compounds being liable to absorption. In the body the parent compounds are reconjugated to glucuronides, but otherwise do not undergo any further metabolism in the body and are excreted in the urine. Daidzein may be metabolized the colonic microflora to equol or to O-demethyl-angolensin (O-Dma) and genistein may be metabolized to p-ethyl phenol. Daidzein, genistein, equol, and O-Dma are the major phytoestrogens detected in the blood and urine of humans and animals.
Once ingested several factors influence the bioavailability of isoflavones. For example, when assessed for urinary isoflavone recovery in postmenopausal women consuming either tempeh, a fermented soybean product, or a comparable quantity of soybean pieces from an unfermented soybean product, urinary isoflavone recovery was greater for the tempeh. The presence of fiber in the diet has been shown to correlate positively with urinary excretion of phytoestrogens. Several investigators have reported that individual variability in colonic microflora plays an important role in determining the preferred pathways of isoflavone metabolism and the bioavailability of isoflavones.
Bifidogenic factors are those elements that help the body increase its levels of beneficial bacteria. These include substances such as N-acetylglucosamine, lactulose found in milk and milk products, and fructooligosaccharides(FOS). One critical factor influencing the bioavailability of isoflavones is soluble fiber, a primary food source for the friendly intestinal bacteria Lactobacillus acidophilus and Bifidobacterium bifidus. Without an adequate supply of food that they specifically live on, these friendly bacteria cannot thrive. This also explains why antibiotics frequently contribute to female health problems, since antibiotics destroy both the bacterial infection for which they are prescribed and a woman""s friendly intestinal flora, which allows other unfriendly flora to proliferate. As a result, a woman taking tetracycline for acne may find herself dealing with vaginal yeast infections and post-menopausal-syndrome (PMS). An imbalance in bowel flora can lead to an imbalance in circulating estrogen.
Diets high in soluble and insoluble fiber and low in fat (less than 25 percent of daily calories) result in a significant increase in levels of hormonally activated phytoestrogens as reported in the American Journal of Clinical Nutrition, 1989, vol. 49, and the American Journal of Nutrition, 1991, vol. 54. The examples of such beneficial fiber include apple pectin, guar gum, fructooligosaccharides (FOS). FOS are a class of sucrose molecules (glucose-fructose disaccharides) to which one, two or three additional fructose molecules have been added. FOS are nutrients that sustain and stimulate helpful microorganisms. It is of interest that the digestive system does not break down FOS. Rather, they reach the lower intestines intact where they are devoured by the xe2x80x9cfriendly bacteriaxe2x80x9d without significantly assisting any of the xe2x80x9cunfriendly bacteria.xe2x80x9d
Dietary fiber has a considerable effect on function and morphology throughout the gastrointestinal tract. The effect of fiber on the intestinal tract is in part a function of residence or transit time. Fibers also affect the mucosal, absorptive ability and luminal contents throughout the gastrointestinal tract. Many of the effects of ingested fiber on the colon relate in part to its being broken down in this portion of the gut. Such fiber breakdown is an anaerobic process and is called fermentation. For every 20 gm of fiber broken down in the human colon each day, approximately 200 mM of short chain fatty acid (SCFA) will be produced, of which about 62 percent will be acetate, 25 percent propionate, and 16 percent butyrate. The SCFA produced by colonic fermentation of dietary residues, such as soluble fiber and undigested starch, are the fuels preferred by the colonic mucosa.
The gastrointestinal tract, like all tissues, requires nutrients to support cell turnover and metabolism. Failure to maintain normal mucosal structure can lead to impaired barrier function in the gut and increased intestinal permeability. If marked mucosal atrophy has occurred, the reintroduction of enternal nutrients may be difficult. Preservation of the gut mucosa may prevent infection, limit morbidity, and enhance absorption and metabolism of nutrients.
It has been proposed that glutamine-containing nutrition solutions could provide specific nutritional support for gastrointestinal tissues. Additional studies have revealed the importance of short chain fatty acids as being preferentially utilized by the colonocyte. It has been reported that specific fuels, such as glutamine and short chain fatty acids have stimulatory effects on intestinal structure and function.
The massive turnover of cells within the gastrointestinal tract requires a constant supply of readily available energy. Trophic effects of diamines, free fatty acids, and pectin have been clearly demonstrated. Increasing evidence suggests that dietary amines promote direct, nonhormonal stimulation of specific mucosal enzymes, such as ornithine decarboxylase. These enzymes are required for polyamine biosynthesis, and their suppression leads to inhibition of mucosa DNA synthesis.
The intestine is a major site of glutamine consumption and, in turn, has high glutaminase activity. Glutamine provides nitrogen for a number of biosynthetic pathways, serving as a precursor to the purine and pyrimide rings of nucleic acids and nucleotides, and is an important constituent of proteins and a precursor of amino sugars. Although it has been known for many years that glutamine is essential for growth of many types of rapidly dividing cells in culture, it later became apparent that enterocytes and colonocytes actively and preferentially metabolize this amino acid.
The increase in intestinal cellularity that occurs when glutamine is added to nutrition solutions suggests that inadequate nutrient delivery plays a part in the intestinal atrophy associated with parenteral feeding. It is not yet clear whether glutamine has its impact on the intestine as a metabolic fuel, as a precursor of metabolites that are essential for cellular replication, or as a regulator of enterotrophic hormones. The relationship between glutamine and growth factors in the gut is speculative at the present time, but studies have indicated that glutamine may interact with specific growth factors.
While maximal glutamine uptake is by the enterocytes of the small intestine, colonocytes also have the capacity to utilize short chain fatty acids(SCFA) which are produced in the mammalian intestinal tract as by-products of anaerobic bacterial fermentation of polysaccharides found in dietary fiber. In nonruminants most of this fermentation occurs in the cecum and colon. The straight chain fatty acids of acetate, propionate, and butyrate are the major end-products of bacterial carbohydrate metabolism in the colon.
As mentioned previously, dietary fiber and resistant starch are the principal substrates for hindgut SCFA production in nonruminants, and therefore colonic SCFA production can be altered by changing the dietary content of these substances. The three major SCFAs, once absorbed, are metabolized by the cecal and colonic mucosa. One result of production, absorption, and metabolism of the SCFA is the provision of energy to the host. It has been estimated that the absorption of SCFA from fiber fermentation may provide from 5 to 30 percent of the daily energy requirements.
In summary, glutamine is not only essential for the growth of many types of rapidly dividing cells in culture, it has been also well documented that enterocytes and colonocytes actively and preferentially metabolize this amino acid. Unlike other tissues, the gut has adapted to preferentially metabolize glutamine since the free ammonia produced readily diffuses into the portal blood and is extracted by the liver before reaching the systemic circulation. Glutamine is metabolized similarly whether it enters the mucosal cells from the lumen or from the blood. When fiber polysaccharide residue reaches the cecum(residue that cannot be digested by the enzymes of the upper gastrointestinal tract), it produces short chain fatty acids(SCFA) as by-products of bacterial fermentation. SCFA are the preferred respiratory fuels for the colonic mucosa. Therefore, according to the present invention the combination of glutamine, fiber and a phytoestrogen provides an improved metabolic environment for enterocytes and colonocytes, which in turn enhances the metabolism and bioavailability of phytoestrogens.
The compositions of this invention may contain single or combinations of phytoestrogens. A preferred combination of the phytoestrogens includes daidzin and genistin having a molar ratio of between about 15:1 to about 1:1. As a possible variant, the combination can include daidzin and genistin in equimolar concentrations. At least 2%(by weight) of the phytoestrogens can be in forms of aglycones. The dosage amount of total isoflavones(genistein, daidzein and glycitein) can vary from about 25 mgs to about 1,000 mgs daily.
These compositions may also include a non-toxic inert carrier or diluent in admixture with the above mentioned active ingredients. Examples of such non-toxic, inert carriers include wheat starch, sodium carboxymethyl cellulose, cellulose, maltodextrin, fructose, sucrose, soy flour, sorbitol, mannitol, and corn syrup.
The administration of the composition of the present invention, which enhances isoflavone availability, would be in accordance with a predetermined regimen. This would be at least once weekly, preferably on a daily basis and over an extended period of time, generally for at least one month, more usually for at least three months, and as a chronic treatment that could last for one year or more, possibly including the life of the subject. There are no restrictions on age and duration for using the new compositions as dietary supplements.
The dose administered will depend upon the frequency of administration, the blood level desired, other concurrent therapeutic treatments, the severity of the condition, whether the treatment is for prophylaxis or therapy, and the like. The amount of phytoestrogen(e.g. isoflavones) administered per day may be within a range of 25 mg to 1000 mg, preferably 200 mg, which corresponds to the amount of isoflavones naturally occurring in 50-75 g of raw soybeans. This is the average amount of soybeans consumed daily in an Oriental diet. A 200 mg dose of isoflavones is functionally equivalent to the average daily dose of conjugated steroidal estrogen used in hormone replacement therapy. When the above mentioned compositions are administered to a mammalian subject for therapeutical purposes, they are preferably administered orally in a dose of 0.15 to 35 g of active ingredients per day. By active ingredients, it does not mean only the phytoestrogens, but also the fiber and glutamine mentioned in the compositions as well. The optimum dosage of course depends on the body weight of the subject as well as the therapeutic purpose of the administration.
When the mammalian subject is a human, the daily dosage of the composition should be within the following ranges: 0.15 to 35 grams per day. More preferably, the daily dosage of the composition administered is within a range of 1 to 35 grams. The most preferred administration regimen of the composition of the present invention is daily dosage of 2-30 grams.
The compositions may also be employed as dietary supplements for mammalian subjects. When the new compositions are employed as dietary supplements, they are preferably administered orally as tablets or capsules, or they may be mixed with food.
The composition of this invention may be made in a variety dosage forms, such as tablets, pills, capsules, powders, solutions, dispersions, food products, and the like. The composition is formulated with physiologically acceptable carriers and optionally stabilizers, colorants, and flavoring agents.
When the new compositions are employed as dietary supplements, they may be admixed with the mammalian subject""s food rather than given as individual compositions in tablet or capsule form. Dietary wafers and liquid supplements which contain all of the active ingredients of the dietary supplement in unit dosage form are especially contemplated.

Preparation of fiber, L-glutamine and a soy derivative for the purpose of enhancement of isoflavone bioavailability


A removable shoe heel assembly that allows removal of a woman's shoe or boot heel, preferably a circular shaped housing unit configured to the underside of a woman's shoe or boot shank having a gravity lock to prevent movement when the removable shoe heel is attached. The gravity lock settles into a first furrow disposed in the housing unit and falls into a second furrow disposed in the removable shoe heel when turned upright, in a vertical position, both parts having a connecting means and a receiving means, respectively. By turning the woman's shoe or boot upside down the gravity lock falls into the first furrow area thereby making removal and reattachment of the removable shoe heel possible.

The present invention relates to women's footwear, either a shoe or boot that has no means of changing styles due to the current nature of permanent heel attachment. The invention described herein allows women to change any shoe style with a new heel, at the discretion of the wearer. The invention is therefore of great use for women who desire to express individual style or need to transport many shoes styles when traveling. The current method of securing a heel relies on nails, brads, cement, etc. and is currently permanently secured. Although shoe heels are permanently secured they do, however, break off. The current invention herein is neither obvious nor anticipated, whereby a more secure method is invented and resists breakage and allows women the great advantage of changing the design of any pair of shoes in this shoe line.
There have been patents for shoe heels that are removable; however there are none with the current method that uses the present invention, herein, to secure a removable shoe heel and prevent removal until desired. Accordingly, what is desired, and has not heretofore been developed and is new and unobvious, is a removable shoe heel assembly. It is further desired that the shoe maintain the basic appearance of a typical shoe. Finally, it is desired that the method of making a removable women's shoe or boot heel be easy to manipulate with no need for outside tools or pieces that one could lose or misplace. The related art follows:
U.S. Pat. No. 6,631,570 B1 Walker. Oct. 14, 2003
U.S. Pat. No. 6,442,871 B2 Doerer, Sep. 3, 2002
U.S. Pat. No. 5,477,625 A Goldsmith, Dec. 26, 1995
U.S. Pat. No. 4,400,893 A Musci, Aug. 30, 1983
Walker invented a product that could eventually twist apart, the present invention has a locking part that prevents accidental movement. Goldsmith uses a strap that could eventually harm the wearer that is also unsightly, and uses a part that could eventually become lost, the present invention that I have designed has no parts to lose and nothing that could harm the wearer. Musci invented parts that will become easily breakable due to the nature of the design, the new invention has no parts that will easily break thereby making the invention a wearable shoe that possesses many style changes and will be successful in the market.
U.S. Pat. No. 2,050,644 A Book, 18-1936
U.S. Pat. No. 2,187,167 A Mayor, 01-1940
U.S. Pat. No. 2,582,551 A Gerhardus, 01-1952
U.S. Pat. No. 2,795,866 A Perguia, 06-1957
U.S. Pat. No. 2,795,867 A Zuckerman et al, 06-1957
U.S. Pat. No. 4,219,946 A Baum, 09-1980
U.S. Pat. No. 5,675,916 A Lewis, 10-1997
US-2010/0139123 A1, Alan et al, 06-2010
Book uses a screw penetrating from the heel tip to the shoe sole. The design could cause the heel to fracture or break with normal use causing injury to the wearer and has ancillary parts that could be lost. The Applicant's invention seats a removable housing assembly in the shoe sole and heel and uses a locking system, thus creating a very secure and easy to operate design with no ancillary parts to lose and is not an assumption or supposition of Book.
Mayor seeks to disconnect a portion of a shoe heel with a sliding action so as to re-connect a lift or heel tip. This design is distinguishingly different from the Applicant's invention because Applicant wishes to remove the entire heel from the sole to attach a new and different style of heel and uses a removable housing assembly in the heel and sole with a gravity lock, and is not assumed or supposed by Mayor.
Gerhardus relates to a heel lifting device with a tongue and groove that is unrelated to the Applicant's invention. Gerhardus also has an unsightly design while the Applicant's invention uses a removable housing assembly in the sole and heel creating no visual difference from a conventional shoe when attached.
Perugia uses a mortise slide and lugs and tenon that slides forward and backward. This could create injury to the wearer due to premature disengagement. The Applicant's invention substantially differs from Perugia and uses a removable housing assembly in the sole and heel with a gravity lock that prevents any movement or disengagement.
Zuckerman uses a shoe stiffener with an enlarged plate and dovetail grooves whereby a pin is inserted by pulling up the shoe sole. By contrast, the Applicant's invention uses a removable housing assembly in the sole and heel with a gravity lock and has no additional parts to insert for placement and is not assumed or supposed by Zuckerman.
Baum uses a screw method of securing a heel; however, no reference is made for a pass through slot or locking device, that when attached to the shank, would create a very durable attachment and prevent movement. The Applicant's invention embodies a design that was not assumed, and is non-obvious and addresses the issue of easily removing the heel, locking another choice of heel when desired, by using a removable housing assembly in the sole and heel with a gravity lock.
Lewis uses another method of a screw device and a plug, using manual insertion under the sole. The Applicant's invention uses no ancillary parts that require manual adjustment and substantially differs from Lewis.
Alan uses an unsightly design with an off-putting sole/heel that will require very costly retooling and overhead. The use of a pin extending through to the shoe heel tip could cause cracking or breakage during normal wear due to force and pressure. Also, the use of the shoe heel tip to remove the heel requires much time to operate. The Applicant's current invention uses easily manufactured parts, making it easy and cost effective to retrofit the current method of shoe making. Also, the current invention uses a removable housing assembly in the sole and heel taking seconds to operate that locks into place, and substantially differs from and is not a conclusion or supposition of Alan's.

Removable shoe heel assembly for women's footwear


Systems and methods for capturing image data using a line scan camera. In an embodiment, a line scan camera captures image data of a sample as a plurality of image stripes. A processor may coarsely align two or more of the plurality of image stripes according to a synchronization process while the line scan camera is capturing at least one of the plurality of image stripes. Subsequently, the processor may also finely align the two or more image stripes using pattern matching.

Field of the Invention
The present invention relates generally to the field of virtual microscopy and pertains more specifically to data management for very large digital imaging files captured by a high resolution linear-array-based microscope slide scanner.
Related Art
Conventional scanners typically digitize a region of a physical specimen at a desired resolution. As the desired resolution increases, the scanning process becomes more technically challenging. Similarly, the scanning process becomes more challenging as the region of interest increases or as the available scanning time decreases. Furthermore, the efficiency with which the digitized data can be viewed on a monitor is often critical to the overall utility of conventional scanning applications.
Recent technical advances in conventional sensors, computers, storage capacity, and image management have made it possible to digitize an entire microscope slide at diagnostic resolution, which is particularly desirable. Diagnostic resolution is the resolution required for a trained technician or clinician to make a diagnosis directly from a computer monitor, rather than making a diagnosis by looking through the eyepieces of a conventional microscope. Diagnostic resolution varies by sample type, for example, the diagnostic resolution required for a skin biopsy specimen is typically lower (i.e., diagnosis requires a lower resolution) than the diagnostic resolution required for other types of biopsy specimens.
Although now technically possible, digitizing an entire microscope slide at a diagnostic resolution remains a formidable challenge. Any practical solution must capture immense amounts of high quality imagery data in a relatively short amount of time. FIG. 1 is a graph diagram plotting the limiting resolution in micrometers ("μm") of an optical system with realistic condenser settings versus the numerical aperture ("NA") for the optical system's microscope objective lens. The limiting resolution is defined as the smallest distance that can be resolved by the optical system. For example, in an optical system that is designed and manufactured appropriately, the limiting resolution would be the minimum spatial dimension that can be observed by the human eye.
As shown in the graph, the limiting resolution for an objective lens with a 0.3 NA is approximately 1.5 μm. Moreover, the limiting resolution for an objective lens with a 0.4 NA improves to about 1 μm while the limiting resolution for an objective lens with a 0.8 NA improves to an even better 0.5 μm. At this juncture, it is important to note that the limiting resolution is independent of magnification and depends solely on the numerical aperture of the objective lens.
Conventional systems that digitize a microscope specimen without losing any details available to the human eye require the dimension of a detector element to be no larger than one half the corresponding limiting resolution distance. This 2-pixel requirement is based on the well-known Nyquist sampling theorem. It should be clear that for a 2-dimensional imaging system, the 2-pixel requirement translates into an array of 2 pixels by 2 pixels. Stated differently, if the limiting resolution is 1 μm, then it is necessary to digitize the specimen at 0.5 μm per pixel (or better) to capture all of the information that is available to the human eye through the objective lens.
FIG. 2 is a graph diagram plotting the scanning resolution in pixels per inch ("ppi") versus the numerical aperture of an objective lens. As shown in the graph, an objective lens with a 0.3 NA requires a scanning resolution of at least 38,000 ppi. This resolution is required to capture all of the details provided by the 0.03 NA objective lens and viewable by the human eye. Similarly, an objective lens with a 0.4 NA requires a scanning resolution of at least 50,000 ppi while an objective lens with a 0.8 NA requires a scanning resolution of at least 100,000 ppi.
FIG. 3 is a graph diagram plotting the scanning resolution in pixels per inch versus the resulting uncompressed file size in megabytes ("MB") for a one square millimeter ("mm") region. The graph pertains to regions captured as 24-bit pixels (3 color channels, 8-bits per channel). As illustrated, a 1 mm2 region at 38,000 ppi is approximately 8 MB (as captured by an objective lens with a 0.03 NA according to FIG. 2). Similarly, a higher scanning resolution of 50,000 ppi for the same 1 mm2 region would result in a file size of 11 MB while a scanning resolution of 100,000 ppi would result in a file size of approximately 47 MB. As can be seen, the size of the image file increases dramatically as the required scanning resolution, expressed in pixels per inch, increases in relation to the increasing numerical aperture of the objective lens. Thus, as the scanning resolution increases, the image file size increases significantly.
Accordingly, digitizing an entire microscope slide at a diagnostic resolution results in extremely large data files. For example, a typical 15 mm×15 mm slide region at a scanning resolution of 50,000 ppi (i.e., 0.4 NA) would result in a file size of approximately 2.5 gigabytes ("GB"). At a scanning resolution of 100,000 ppi, the resulting file size quadruples to approximately 10 GB for the same 225 square millimeter area of a slide.
There are two basic methods that have been developed for scanning entire microscope slides: (i) conventional image tiling, and (ii) a novel line-scanning method and system developed by Aperio Technologies, Inc. This latter method utilizes a linear-array detector in conjunction with specialized optics, as described in U.S. patent application Ser. No. 09/563,437, entitled "Fully Automatic Rapid Microscope Slide Scanner," which is currently being marketed under the name ScanScope®.
Conventional image tiling is a well-known technique. Image tiling involves the capture of multiple small, statically sized regions of a microscope slide using a traditional fixed-area Charge-Coupled-Device ("CCD") camera, with each capture tile being stored as a separate individual image file. Subsequently, the various image tiles that comprise a specimen are digitally "stitched" together (i.e., alignment) to create a large contiguous digital image of the entire slide.
The number of individual image tiles required to scan a given area of a slide is proportional to the number of pixels that comprise each image tile. A typical video-format color camera has 768×494 pixels, which translates into 1.1 MB of imagery data per image tile. Recalling that a 1 mm2 region of a slide corresponds to 11 MB of imagery data, it follows that approximately 10 non-overlapping image tiles must be captured to digitize one square millimeter of a slide at a scanning resolution of 50,000 ppi. At 100,000 ppi the required number of tiles increases four-fold to 40 image tiles per square millimeter.
It follows that for a typical 15 mm×15 mm slide region, at a scanning resolution of 50,000 ppi, a minimum of 2,250 individual image tiles must be captured. At a scanning resolution of 100,000 ppi, a minimum of 9,000 individual image tiles must be captured. Importantly, each image tile would have a file size of approximately 1.1 MB. In practice, an even larger number of tiles must be captured to provide sufficient overlap between adjacent tiles to facilitate the "stitching" together or alignment of adjacent image tiles.
Conventional image tiling systems generally take hours to capture and align the thousands of tiles required to digitize an entire microscope slide. Image capture times are significantly increased by the need to wait for the CCD camera to stabilize after being repositioned and before acquiring an image tile. This wait time is necessary to ensure that the captured image does not blur. Practical limitations in data processing speeds also make the alignment of large numbers of image tiles extremely slow. In practice, conventional image tiling systems are not able to align large numbers of tiles without creating "stitch lines" and other image artifacts that create computer imaging challenges.
An alternative to image tiling is the afore-mentioned line-scanning method. Rather than using a fixed-area camera to capture thousands of individual image tiles, the line-scanning method employs a linear-array detector in conjunction with a microscope objective lens and other optics to capture a small number of contiguous overlapping image stripes. Unlike the stop-and-go nature of conventional image tiling, the microscope slide moves continuously and at a constant velocity during acquisition of an image stripe. One of the many fundamental advantages of line-scanning over conventional image tiling is that the capture and alignment of a small number of image stripes is significantly more efficient than the capture and alignment of thousands of separately captured image tiles.
For example, a typical 15 mm×15 mm slide region at 50,000 ppi would require 15 image stripes, each with a width of 2,000 pixels, to digitally capture the region. Here, each image stripe would have a file size of approximately 170 MB. At 100,000 ppi, the same region would require 30 image stripes with each stripe comprising approximately 680 MB. The capture of 15 or 30 image stripes for a 15 mm×15 mm area is dramatically more efficient than the capture of 2,250 or 9,000 image tiles at 50,000 ppi or 100,000 ppi respectively. Furthermore, the continuous scanning nature of line-scanning makes it possible to create seamless virtual slides of a region in minutes.
In addition to rapid data capture, line scanning benefits from several advantages that ensure consistently superior imagery data. First, it is possible to adjust the focus of the objective lens from one scan line to the next, in contrast to image tiling systems that are inherently limited to a single focal plane for an entire image tile. Second, because the sensor in a line scanning system is one-dimensional, there are no optical aberrations along the scanning axis. In an image tiling system, the optical aberrations are circularly symmetric about the center of the image tile. Third, the linear detector has a one-hundred percent (100%) fill factor, providing full pixel resolution (8 bits per color channel), unlike color CCD cameras that lose spatial resolution because color values from non-adjacent pixels are interpolated (e.g., using a Bayer Mask).
To handle the immense amounts of data produced by conventional image tiling systems, data management tools have been developed to manage the thousands of relatively small (˜1 MB) image tiles typically generated by such systems. These data management utilities, however, are not suitable for managing a small number of relatively large (˜200 MB) image stripes captured by the line-scanning image striping system.
Therefore, introduction of the superior image striping system and method for digitizing microscope slides has created a need in the industry for a data management system that meets the unique needs imposed by the new technology.

Data management in a linear-array-based microscope slide scanner


An I.S. machine wherein a parison is blown into a bottle in a blow mold. The parison is initially suspended from the neck ring mechanism and the blow molds are displaced to close around the parison below the finish. The neck ring mechanism is displaced away from the mold and a blow head is located on top of the mold to provide final blow. A heat sensor senses when the parison, during reheat has reached the bottom of the mold and supplies a signal to a controller which starts final blow based on the time when this signal was supplied.

The present invention relates to I.S. glass container forming machines and more particularly to the improved control of such machines.
In an I.S. machine a gob of molten glass is formed into a parison within a blank mold and the formed parison is transferred to a blow station where blow molds are closed around the parison, a blow head is positioned on top of the blow molds and the parison is blown by applying xe2x80x9cfinal blowxe2x80x9d. The blown parison is cooled defining a formed bottle that can stand on its own whereupon the blow molds are opened and the bottle is transferred to a dead plate for additional cooling. The time between the closing of the blow molds and the application of final blow is referred to as reheat.
The time when events occur in an I.S. machine are conventionally controlled by an electronic timing drum or sequence controller. Set angles are set by the machine operator for blow molds close, blow head on, and final blow.
It is an object of the present invention to provide an I.S. glass container forming machine which have a better controlled process for forming the bottle in the blow molds.
Other objects and advantages of the present invention will become apparent from the following portion of this specification and from the accompanying drawings which illustrate in accordance with the mandate of the patent statutes a presently preferred embodiment incorporating the principles of the invention.


In one embodiment, a method includes accessing a plurality of generative adversarial networks (GANs) that are each applied to a particular level k of a Laplacian pyramid. Each GAN may comprise a generative model Gk and a discriminative model Dk. At each level k, the generative model Gk may take as input a noise vector zk and may output a generated image {tilde over (h)}k. At each level k, the discriminative model Dk may take as input either the generated image {tilde over (h)}k or a real image hk, and may output a probability that the input was the real image hk. The method may further include generating a sample image Ĩk from the generated images {tilde over (h)}k, wherein the sample image is based on the probabilities outputted by each of the discriminative models Dk and the generated images {tilde over (h)}k. The method may further include providing the sample image Ĩk for display.

In machine learning, a convolutional neural network (e.g., convnet) is a type of feed-forward artificial neural network in which the connectivity pattern between its neurons is inspired by the organization of the animal visual cortex. Individual cortical neurons respond to stimuli in a restricted region of space known as the receptive field. The receptive fields of different neurons partially overlap such that they tile the visual field. The response of an individual neuron to stimuli within its receptive field can be approximated mathematically by a convolution operation. Convolutional networks were inspired by biological processes and are variations of multilayer perceptrons designed to use minimal amounts of preprocessing. They have wide applications in image and video recognition, recommender systems and natural language processing.

Producing higher-quality samples of natural images


The present invention provides a removable shield attachment for hand-held digging tools which is mounted on the tool handle below the tool head so as to not interfere with gripping along the length of the handle. The shield generally comprises a mounting portion adapted to be mounted on the handle below the tool head, a shield portion extending laterally outwardly and upwardly from the mounting portion, and a slot positioned between the mounting portion and the shield portion adapted for passing a blade of the tool head therethrough. In use, the shield portion is positioned above the blade, thereby intercepting debris flying from the blade and towards the worker. The shield is particularly designed for digging tools having a slidably fit tool head that engages an outwardly tapered working end of the handle, with the shield being attached to the handle in the same manner as the tool head itself.

The use of hand-held digging tools or chipping tools, such as pickaxes and mattocks, can pose risk of injury to a worker from flying debris which is thrown out from the blade of the tool head, especially when digging into hard materials like asphalt, cement, ice, hard pan, clay, gravel, roots and so forth. To protect the worker, particularly the face, neck and head area, shield attachments can be attached to the tool to intercept debris flying toward the worker, while still permitting use of the tool. Such shield attachments are also useful for protecting other persons and property in the vicinity of the worker.
Examples of previous shield attachments include those disclosed in U.S. Pat. No. 1,236,968 to Mockel, U.S. Pat. No. 1,336,630 to Kirkpatrick and U.S. Pat. No. 1,358,206 to Higgins. In each of those cases, a shield portion is removably attached to the tool handle by an attaching structure positioned around the handle. In general, the attaching structure is positioned above the tool head, with the shield portion being positioned adjacent the underside of the handle and between the blade and the worker. The position of the attaching structure above the tool head, however, interferes with the ability of the worker to grip the full length of the handle adjacent the tool head during the initiation of the stroke, which is often desired for achieving maximum force when using the tool. Further, some prior art designs utilize wire as an attaching structure, which may not adequately secure the shield portion in place, while other designs require the use of clamps and tools to attach the shield portion.
There is, therefore, a need in the art for an improved shield attachment for hand-held digging tools.

Shield attachment for hand-held digging tools