Apparatus for packaging articles in clear clamshell packages includes a pair of parallel relatively narrow, laterally spaced apart conveyor belts that support there-between a package in open position by its opposing side peripheries. A stack of packages is supported in nested configuration adjacent the front end of the conveyor and de-nester mechanism withdraws packages there-from and places them on the conveyor.

1. Field of the Invention
The present invention relates generally to apparatus and methods for packaging clear plastic packages for small articles. More particularly it relates to UV packaging systems for clamshell type packages.
2. Description of the Prior Art
It has become popular to secure small articles of commerce in clear plastic packages such as clamshell-type packages and that permit prospective purchasers a view of the product while providing a seal against tampering and pilferage. Advances in the industry have led to the development of UV adhesive based systems whereby articles of commerce and associated product information card are placed in the cavity of a clamshell package, adhesive applied along "proud points" or raised male portions of the package, then the lid is manually closed to bring the proud points into corresponding grooves, and then the closed package is sent to a UV illumination chamber for instant curing and sealing.
Although improved packaging has resulted, conventional methods for producing these packages are labor intensive and remain limited by interruptions, excessive dwell-time and pauses.

Apparatus and method for packaging articles in clear plastic packages

Abstract: As the package is advanced a robotic arm picks and places articles of commerce and associated product information card in the package cavity. A rotating roller coated with UV-responsive adhesive coats raised male surfaces of the advancing package. Next an air knife sends a jet of air upwardly to cause the open package lid to rotate upwardly to cover the article-receiving portion. A driven roller presses the lid downwardly to fully close it and cause the adhesive coated surfaces to fully engage the corresponding grooves on the article-receiving portion. The package is then delivered to a UV illumination chamber where the UV adhesive in instantly cured to seal the package.


A method to generate a beamforming vector by a terminal includes receiving information on a first precoding matrix and a second precoding matrix from a serving base station; and generating a beamforming vector by linearly combining the first precoding matrix and the second precoding matrix.

A multi input multi output (MIMO) communication system, which is an antenna system that can perform a multi input and output, is a technology that can transmit data to several route by increasing an antenna of a base station and a terminal to two or more and detect signals received from a receiving end to each route to reduce interference and reduce each transmission speed.
The terminal using a multi antenna can control a transmission direction of data using a beamforming vector. However, since the beamforming vector can cause the interference between neighboring cells, a need exists for a method to generate a beamforming vector in consideration of the interference between the neighboring cells.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.

Method to generate beamforming vector and provide the information for generating beamforming vector

Electronics and Telecommunications Research Institute

Industry Academic Cooperation Foundation of Kyunghee University


A system and method for generating an m-dimensional signature vector in a computing device is provided. The signature vector may be generated from a plurality of key-value pairs, each comprising a unique identifier and an associated non-zero value. Each element of the m-dimensional signature vector is calculated based on a summation of a plurality of terms. Each of the terms is calculated from a respective key-value pair by generating a seed based on the key of the respective key-value pair and an element identifier associated with the vector element being calculated; generating a pseudo-random number from the generated seed; and multiplying the pseudo-random number by the value of the respective key-value pair, wherein m<<n.

The data produced by an information source may be viewed as a random realization produced from a certain probability distribution that is a unique characteristic of that particular source. Different sources will produce realizations of the data from distinct underlying probability distributions.
An information source is said to be producing sparse data if a typical realization of its data, when transformed by a fixed orthonormal transformation that is a characteristic property of that source, consists of only up to s non-zero values. The source is then said to be "s-sparse under that orthonormal transformation" or "s-sparse in the basis of that orthonormal transformation". As a special case, a source can be sparse under the identity orthonormal transformation which leaves the data unchanged, and in such a case the source is said to be "s-sparse its own domain".
For example, if the source produces vectors of dimensionality 10000, that is, vectors having 10000 elements, but a typical realization of the vector has only up to 10 elements with a non-zero value, then that source may be considered to be sparse, or more accurately 10-sparse, in its own domain. On the other hand if a typical realization of the vector, when transformed by the Fourier transform, has only up to 10 non-zero entries, then the source is said to 10-sparse in the Fourier or frequency domain. It is important to note that it is not generally known a-priori which elements of a realization, in its own domain or after a fixed transformation will be non-zero. It also may not always be known a-priori what the associated orthonormal transformation is. Typically, only the sparsity of the source, s, or at least an upper bound on it, is known with some certainty.
Although sparsity is, strictly speaking, a property of a random information source, it is an accepted terminology in the field to say that its data is sparse, where the data is implicitly presumed to be a random variable. It is not meaningful to talk of the sparsity of a single deterministic realization of data, since any deterministic realization is always sparse in its own basis.
A characteristic of sparse data is that it may be easily compressed. The compressed data may be used as a signature of the data for data analysis purposes, or may be subsequently de-compressed, effectively recreating the original sparse vector, prior to use.
A common example of compression is that of compressing an image. The image date may be compressed prior to transmission over a network and later decompressed for display without impacting, or having an acceptable impact on, the information to be conveyed, that is the image. The compressed image may be considered a signature of the image and may be used as a representation of the data. For example the compressed data of an image could be used as a fingerprint of the uncompressed image.
It is desirable to have a technique of generating a compressed representation of a high dimensionality sparse data that does not require huge memory allocation in order to calculate the compressed representation. Moreover, if the data is sparse in its own domain, it is desirable to exploit this property to reduce the number of computation need in computing the signature to O(s), as well.

Signature representation of data having high dimensionality


A semiconductor device (2) includes a semiconductor substrate (12) having a surface (13) formed with a first recessed region (20). A first dielectric material (60) is deposited in the first recessed region and formed with a second recessed region (76), and a second dielectric material (100) is grown over the first dielectric material to seal the second recessed region.

The present invention relates in general to semiconductor devices and, more particularly, to integrated circuits having components formed on a low capacitance region of a semiconductor die.
Semiconductor technology continues to scale transistors to have smaller dimensions in order to provide increased functionality and a higher frequency capability. For example, wireless communication devices often use integrated circuits that include high-density digital signal processing functions on the same die as analog circuits operating at frequencies in excess of five gigahertz.
However, some integrated circuit components, such as passive devices, are not readily scalable. These devices have relatively high parasitic substrate capacitances, which often limits the overall frequency capability of an integrated circuit. For example, inductors are not easily reduced in size without reducing their quality factor or inductance to an unacceptable level, and bonding pads are not scalable because of the need to attach wire bonds to the bonding pads.
A variety of techniques have been tried to reduce the parasitic capacitances of passive integrated circuit components. One such technique is to form the components over a low permittivity material. However, current low permittivity materials are limited to film thicknesses that are too thin to produce a substantial reduction in parasitic capacitance. Another approach is to form the components over a thick dielectric film in which are formed air gaps or voids that reduce the overall permittivity of the dielectric film. Previously, voids were formed using thermally grown dielectric films to form the trench, and deposited films to seal them. However, voids made with such films introduce substantial stress in a semiconductor substrate, which degrades the performance and reliability of the integrated circuit. Also, these voids are not optimized for reducing capacitance due to the relatively high dielectric constant of the films used to form them. Furthermore, the voids are filled with these films during the sealing process producing a void with increased dielectric constant. Other schemes reduce the stress by producing fewer voids or voids with only a limited volume, which has a correspondingly limited effect on parasitic capacitance. Moreover, in order to avoid contaminating the transistors or reducing the die yield or reliability, complex and costly schemes are required to enable the integration of the low permittivity structures with active devices such as transistors.
Hence, there is a need for a low capacitance structure and method of making an integrated circuit that maintains a low cost while reducing die stress and avoiding the introduction of contaminants into the integrated circuit.

Semiconductor device and method of providing regions of low substrate capacitance

Semiconductor Components Industries, L.L.C.


The passage of a container along a conveyor is lubricated by applying to the container or conveyor a mixture of a water-miscible silicone material and a water-miscible lubricant. The mixture can be applied in relatively low amounts, to provide thin, substantially non-dripping lubricating films. In contrast to dilute aqueous lubricants, the lubricants of the invention provide drier lubrication of the conveyors and containers, a cleaner conveyor line and reduced lubricant usage, thereby reducing waste, cleanup and disposal problems.

In commercial container filling or packaging operations, the containers typically are moved by a conveying system at very high rates of speed. Typically, a concentrated lubricant is diluted with water to form an aqueous dilute lubricant solution (i.e., dilution ratios of 100:1 to 500:1), and copious amounts of aqueous dilute lubricant solutions are typically applied to the conveyor or containers using spray or pumping equipment. These lubricant solutions permit high-speed operation of the conveyor and limit marring of the containers or labels, but also have some disadvantages. First, dilute aqueous lubricants typically require use of large amounts of water on the conveying line, which must then be disposed of or recycled, and which causes an unduly wet environment near the conveyor line. Second, some aqueous lubricants can promote the growth of microbes. Third, by requiring dilution of the concentrated lubricant dilution errors can occur, leading to variations and errors in concentration of the aqueous dilute lubricant solution. Finally, by requiring water from the plant, variations in the water can have negative side effects on the dilute lubrication solution. For example, alkalinity in the water can lead to environmental stress cracking in PET bottles.
When an aqueous dilute lubricant solution is used, it is typically applied at least half of the time the conveyor is running, and usually it is applied continuously. By running the aqueous dilute lubricant solution continuously, more lubricant is used than is necessary, and the lubricant concentrate drums have to be switched out more often than necessary.
"Dry lubes" have been described in the past as a solution to the disadvantages of dilute aqueous lubricants. A "dry lube" historically has referred to a lubricant composition with less than 50% water that was applied to a container or conveyor without dilution. However, this application typically required special dispensing equipment and nozzles and energized nozzles in particular. Energized nozzles refer to nozzles where the lubricant stream is broken into a spray of fine droplets by the use of energy, which may include high pressures, compressed air, or sonication to deliver the lubricant. Silicone materials have been the most popular "dry lube". However, silicone is primarily effective at lubricating plastics such as PET bottles, and has been observed to be less effective at lubricating on glass or metal containers, particularly on a metal surface. If a plant is running more than one type of container on a line, the conveyor lubricant will have to be switched before the new type of container can be run. Alternatively, if a plant is running different types of containers on different lines, the plant will have to stock more than one type of conveyor lubricant. Both scenarios are time consuming and inefficient for the plant.
It is against this background that the present invention has been made.

This patent is subject to a terminal disclaimer.


Disclosed herein is an active metabolite (“M20”) of a molecule that is useful as a thrombin receptor antagonist: Also disclosed are formulations of this compound, synthetic routes to this compound, and methods of treating a variety of cardiovascular conditions, including acute coronary syndrome and peripheral arterial disease, and of effecting secondary prevention, by orally administering the active metabolilte.

Schering Corp. is developing a thrombin receptor antagonist ("TRA") for use in a variety of cardiovascular applications, including treatment of acute coronary syndrome ("ACS") and secondary prevention. The active pharmaceutical ingredient ("API"), SCH 530348, has completed phase I and II clinical trials, and is currently in phase III trials. The development of an understanding of the metabolism of SCH 530348 is both a desirable progression in the science and a necessary step in the commercialization of this thrombin receptor antagonist.
Thrombin is known to have a variety of activities in different cell types and thrombin receptors are known to be present in such cell types as human platelets, vascular smooth muscle cells, endothelial cells and fibroblasts. It is therefore possible that thrombin receptor antagonists, also known as protease activated receptor (PAR) antagonists, will be useful in the treatment of thrombotic, inflammatory, atherosclerotic and fibroproliferative disorders, as well as other disorders in which thrombin and its receptor play a pathological role.
U.S. Pat. No. 7,304,078 discloses a genus of compounds, including a specific thrombin receptor antagonist compound identified as Example 2, herein identified as SCH 530348. SCH 530348 has the following structure:
and the following chemical formula: Ethyl[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]dodecahydro-1-methyl-3-oxonaphtho[2,3-c]furan-6-yl]carbamate. SCH 530348 exhibits good thrombin receptor antagonist activity (potency) and selectivity, and is currently in development by Schering Corp. Co-pending U.S. patent application Ser. No. 10/705,282, herein incorporated by reference, discloses a variety of indications and combination formulations for thrombin receptor antagonists including SCH 530348. A preferred crystalline form of the bisulfate salt of SCH 530348 is disclosed in U.S. Pat. No. 7,235,567. U.S. patent application Ser. Nos. 11/771,571; 11/771,520; and 11,860,165 disclose capsule formulations, tablet formulations and lyophilized formulations (respectively) of SCH 530348, and methods of treating various conditions by administering same.
The use of a small subset of thrombin receptor antagonists to treat a variety of conditions and diseases is disclosed in U.S. publication no. 04/0192753. The prevention of complications associated with cardiopulmonary bypass surgery by administration of a thrombin receptor antagonist is taught in U.S. application Ser. No. 11/613,450. Methods of preventing cardiac events after percutaneous intervention ("PCI," e.g., angioplasty, stent introduction) are disclosed in U.S. application Ser. No. 12/051,504. Substituted thrombin receptor antagonists are disclosed in U.S. Pat. Nos. 6,063,847; 6,326,380; and 6,645,987 and U.S. publication nos. 03/0203927; 04/0216437A1; 04/0152736; and 03/0216437. All of the herein cited references are incorporated in their entirety.
It would be beneficial to identify any active metabolites of SCH 530348 that persist in the body after dosing. The invention seeks to provide these and other benefits, which will become apparent as the description progresses.

Active metabolite of a thrombin receptor antagonist


The present invention relates to the manufacture of conjugated linoleic acid, and in particular, to dietary supplements, feeds and food products containing conjugated linoleic acid. Accordingly, processes for producing conjugated linoleic acid of high purity and acid value are disclosed. These processes utilize alcoholate catalysts and esters of sunflower oil, safflower oil, or corn oil as the source of linoleic acid. The esters of conjugated linoleic acid produced by the process can be used in animal feeds and in food products suitable for human consumption. Furthermore, the esters can be converted into free fatty acids or incorporated into triglycerides.

The present invention relates to the manufacture of conjugated linoleic acid, and in particular, to feeds and food products containing conjugated linoleic acid.
In 1978, researchers at the University of Wisconsin discovered the identity of a substance contained in cooked beef that appeared to inhibit mutagenesis. The substance was found to be a mixture of positional isomers of linoleic acid (C18:2) having conjugated double bonds. The c9,t11 and t10,c12 isomers are present in greatest abundance, but it is uncertain which isomers are responsible for the biological activity observed. It has been noted from labeled uptake studies that the 9,11 isomer appears to be somewhat preferentially taken up and incorporated into the phospholipid fraction of animal tissues, and to a lesser extent the 10,12 isomer. (Ha, et al., Cancer Res., 50: 1097 [1990]).
The biological activity associated with conjugated linoleic acids (termed CLA) is diverse and complex. At present, very little is known about the mechanisms of action, although several preclinical and clinical studies in progress are likely to shed new light on the physiological and biochemical modes of action. The anticarcinogenic properties of CLA have been well documented. Administration of CLA inhibits rat mammary tumorigenesis, as demonstrated by Birt, et al., Cancer Res., 52: 2035s [1992]. Ha, et al., Cancer Res., 50: 1097 [1990] reported similar results in a mouse forestomach neoplasia model. CLA has also been identified as a strong cytotoxic agent against target human melanoma, colorectal and breast cancer cells in vitro. A recent major review article confirms the conclusions drawn from individual studies (Ip, Am. J. Clin. Nutr., 66 (6 Supp): 1523s [1997]).
Although the mechanisms of CLA action are still obscure, there is evidence that some component(s) of the immune system may be involved, at least in vivo. U.S. Pat. No. 5,585,400 (Cook, et al., incorporated herein by reference) discloses a method for attenuating allergic reactions in animals mediated by type I or TgE hypersensitivity by administering a diet containing CLA. CLA in concentrations of about 0.1 to 1.0 percent was also shown to be an effective adjuvant in preserving white blood cells. U.S. Pat. No. 5,674,901 (Cook, et al.), incorporated herein by reference, disclosed that oral or parenteral administration of CLA in either free acid or salt form resulted in elevation in CD-4 and CD-8 lymphocyte subpopulations associated with cell-mediated immunity. Adverse effects arising from pretreatment with exogenous tumor necrosis factor could be alleviated indirectly by elevation or maintenance of levels of CD-4 and CD-8 cells in animals to which CLA was administered. Finally, U.S. Pat. No. 5,430,066, incorporated herein by reference, describes the effect of CLA in preventing weight loss and anorexia by immune stimulation.
Apart from potential therapeutic and pharmacologic applications of CLA as set forth above, there has been much excitement regarding the use of CLA nutritively as a dietary supplement. CLA has been found to exert a profound generalized effect on body composition, in particular redirecting the partitioning of fat and lean tissue mass. U.S. Pat. No. 5,554,646 (Cook, et al.), incorporated herein by reference, discloses a method utilizing CLA as a dietary supplement in which pigs, mice, and humans were fed diets containing 0.5 percent CLA. In each species, a significant drop in fat content was observed with a concomitant increase in protein mass. It is interesting that in these animals, increasing the fatty acid content of the diet by addition of CLA resulted in no increase in body weight, but was associated with a redistribution of fat and lean within the body. Another dietary phenomenon of interest is the effect of CLA supplementation on feed conversion. U.S. Pat. No. 5,428,072 (Cook, et al., incorporated herein by reference), provided data showing that incorporation of CLA into animal feed (birds and mammals) increased the efficiency of feed conversion leading to greater weight gain in the CLA supplemented animals. The potential beneficial effects of CLA supplementation for food animal growers is apparent.
Another important source of interest in CLA, and one which underscores its early commercial potential, is that it is naturally occurring in foods and feeds consumed by humans and animals alike. In particular, CLA is abundant in products from ruminants. For example, several studies have been conducted in which CLA has been surveyed in various dairy products. Aneja, et al., J. Dairy Sci., 43: 231 [1990] observed that processing of milk into yogurt resulted in a concentration of CLA. (Shanta, et al., Food Chem., 47: 257 [1993]) showed that a combined increase in processing temperature and addition of whey increased CLA concentration during preparation of processed cheese. In a separate study, Shanta, et al., J. Food Sci., 60: 695 [1995] reported that while processing and storage conditions did not appreciably reduce CLA concentrations, they did not observe any increases. In fact, several studies have indicated that seasonal or interanimal variation can account for as much as three fold differences in CLA content of cows milk. (See e.g., Parodi, et al., J. Dairy Sci., 60: 1550 [1977]). Also, dietary factors have been implicated in CLA content variation, as noted by Chin, et al., J. Food Camp. Anal., 5: 185 [1992]. Because of this variation in CLA content in natural sources, ingestion of prescribed amounts of various foods will not guarantee that the individual or animal will receive the optimum doses to ensure achieving the desired nutritive effect.
Linoleic acid is an important component of biolipids, and comprises a significant proportion of triglycerides and phospholipids. Linoleic acid is known as an xe2x80x9cessentialxe2x80x9d fatty acid, meaning that the animal must obtain it from exogenous dietary sources since it cannot be autosynthesized. Incorporation of the CLA form of linoleic acid may result in a direct substitution of CLA into lipid positions where unconjugated linoleic would have migrated. However, this has not been proven, and some of the highly beneficial but unexplained effects observed may even result from a repositioning of CLA within the lipid architecture at sites where unconjugated linoleic acid would not have otherwise migrated. It is now clear that one source of animal CLA, especially in dairy products, comes from the biochemical action of certain rumen bacteria on native linoleic acid, first isomerizing the linoleic acid to CLA, and then secreting it into the rumen cavity. Kepler, et al., J. Nutrition, 56: 1191 [1966] isolated a rumen bacterium, Butyrivibrio fibrisolvens, which catalyzes formation of 9,11-CLA as an intermediate in the biohydrogenation of linoleic acid. Chin, et al., J. Nutrition, 124: 694 [1994] further found that CLA found in the tissues of rodent was associated with bacteria, since corresponding germ-free rats produced no CLA.
In the development of a defined commercial source of CLA for both therapeutic and nutritional application, a process for generating large amounts of defined material is needed. The problem with most CLA products made by conventional approaches is their heterogeneity, and substantial variation in isoform from batch to batch. Considerable attention has been given to the fact that the ingestion of large amounts of hydrogenated oils and shortenings, instead of animal tallow, has resulted in a diet high in trans-fatty acid content. For example, Holman, et al., PNAS, 88:4830 [1991] showed that rats fed hydrogenated oils gave rise to an accumulation in rat liver of unusual polyunsaturated fatty acid isomers, which appeared to interfere with the normal metabolism of naturally occurring polyunsaturated fatty acids. These concerns were summarized in an early Editorial in Am. J. Public Health, 84: 722 (1974). Therefore, there exists a strong need for a biologically active CLA product of defined composition.
The present invention relates to the manufacture of conjugated linoleic acid, and in particular, to feeds and food products containing conjugated linoleic acid. In some embodiments, the present invention provides methods for producing conjugated linoleic acid with a high acid value comprising: a) providing: i) a composition comprising esters of linoleic acid; and ii) an alcoholate catalyst; b) treating the composition comprising esters of linoleic acid with the alcoholate catalyst to produce a conjugated linoleic acid ester composition; c) treating the conjugated linoleic acid ester composition with alkali to produce a saponified conjugated linoleic acid composition; and d) treating the saponified conjugated linoleic acid composition with a mild acid wash to produce a free conjugated fatty acid composition. In some embodiments, the free conjugated linoleic acid composition has an acid value of greater than 190. In other embodiments, the free conjugated linoleic acid composition has an acid value of from about 190 to 210. In still other embodiments, the mild acid wash has a pH of from about 5 to 7. In further embodiments, step (d) further comprises a plurality of mild acid washes. In some embodiments, the mild acid wash is performed with a citric acid solution. The present invention is not limited to any particular starting oil. Indeed, the composition comprising esters of linoleic acid is derived from an oil selected from the group consisting of safflower, sunflower, and corn oil. The present invention is not limited to the use of any particular alcoholate catalyst. Indeed, the alcoholate catalyst is selected from the group consisting of sodium methylate, potassium methylate, sodium ethylate and potassium ethylate. In still other embodiments, the alcohol is ethanol.
In some embodiments, the present invention provides the conjugated linoleic acid composition produced by the method described in the preceding paragraph. In some embodiments, the composition has an acid value of greater than 190. In other embodiments, the composition has an acid value of from about 190-210. In still other embodiments, the composition is substantially free of esters of conjugated linoleic acid. In further embodiments, the composition comprises less than 1.0% trans-trans fatty acid isomers on molar basis. In some embodiments, food products or capsules comprising the conjugated linoleic acid compositions are provided.
In some embodiments, the present invention provides methods for producing conjugated linoleic acid with a high acid value comprising: a) providing: i) a composition comprising esters of linoleic acid; and ii) an alcoholate catalyst; b) treating the composition comprising esters of linoleic acid with the alcoholate catalyst to produce a conjugated linoleic acid ester composition; c) treating the conjugated linoleic acid ester composition with alkali under conditions such that a saponified conjugated linoleic acid composition comprising residual alcohol is produced; d) injecting a strong acid solution into the saponified conjugated linoleic acid composition under conditions such that an oil phase comprising free conjugated fatty acids and a water phase are produced; and e)immediately separating the oil phase and the water phase under conditions such that re-esterification between the residual alcohol and the conjugated fatty acids is substantially prevented. In some embodiments, the free conjugated linoleic acid composition has an acid value of greater than 190. In other embodiments, the free conjugated linoleic acid composition has an acid value of from about 190 to 210. In still other embodiments, the mild acid wash has a pH of from about 5 to 7. In some embodiments, the separation in step (e) is performed by centrifugal separation. In further embodiments, the strong acid solution has a pH of from about 2 to 3. The present invention is not limited to any particular starting oil. Indeed, the composition comprising esters of linoleic acid is derived from an oil selected from the group consisting of safflower, sunflower, and corn oil. The present invention is not limited to the use of any particular alcoholate catalyst. Indeed, the alcoholate catalyst is selected from the group consisting of sodium methylate, potassium methylate, sodium ethylate and potassium ethylate.
In some embodiments, the present invention provides the conjugated linoleic acid composition produced by the method described in the preceding paragraph. In some embodiments, the composition has an acid value of greater than 190. In other embodiments, the composition has an acid value of from about 190-210. In still other embodiments, the composition is substantially free of esters of conjugated linoleic acid. In further embodiments, the composition comprises less than 1.0% trans-trans fatty acid isomers on molar basis. In some embodiments, food products or capsules comprising the conjugated linoleic acid compositions are provided.
In some embodiments, the present invention provides methods of splitting saponified conjugated linoleic acids comprising: a) providing: i) a composition comprising saponified conjugated linoleic acid ii) a mild acid solution; and b) washing the composition comprising saponified conjugated linoleic acid with the mild acid solution to produce a composition comprising free conjugated linoleic acid. In some embodiments, the methods further comprise step c) repeating step (b) at least one time to produce a free conjugated fatty acid composition. In some embodiments, the free conjugated linoleic acid composition has an acid value of greater than 190. In other embodiments, the free conjugated linoleic acid composition has an acid value of from about 190 to 210. In some embodiments, the mild acid washes have a pH of from about 5 to 7. The present invention is not limited to any particular starting oil. Indeed, the composition comprising esters of linoleic acid is derived from an oil selected from the group consisting of safflower, sunflower, and corn oil. The present invention is not limited to the use of any particular alcoholate catalyst. Indeed, the alcoholate catalyst is selected from the group consisting of sodium methylate, potassium methylate, sodium ethylate and potassium ethylate.
In some embodiments, the present invention provides the conjugated linoleic acid composition produced by the method described in the preceding paragraph. In some embodiments, the composition has an acid value of greater than 190. In other embodiments, the composition has an acid value of from about 190-210. In still other embodiments, the composition is substantially free of esters of conjugated linoleic acid. In further embodiments, the composition comprises less than 1.0% trans-trans fatty acid isomers on molar basis. In some embodiments, food products or capsules comprising the conjugated linoleic acid compositions are provided.
In still other embodiments, the present invention provides methods of splitting saponified conjugated linoleic acids comprising: a) providing i) a composition comprising saponified conjugated linoleic acid and residual alcohol; and ii) a strong acid solution; b) injecting a strong acid solution into the saponified conjugated linoleic acid composition under conditions such that an oil phase comprising free conjugated fatty acids and a water phase comprising residual ethanol are produced; and c) immediately separating the oil phase and the water phase under conditions such that re-esterification between the residual ethanol and the conjugated fatty acids is substantially prevented. In some embodiments, the free conjugated linoleic acid composition has an acid value of greater than 190. In other embodiments, the free conjugated linoleic acid composition has an acid value of from about 190 to 210. In some embodiments, the strong acid solution has a pH of from about 2 to 3. The present invention is not limited to any particular starting oil. Indeed, the composition comprising esters of linoleic acid is derived from an oil selected from the group consisting of safflower, sunflower, and corn oil. The present invention is not limited to the use of any particular alcoholate catalyst. Indeed, the alcoholate catalyst is selected from the group consisting of sodium methylate, potassium methylate, sodium ethylate and potassium ethylate.
In some embodiments, the present invention provides the conjugated linoleic acid composition produced by the method described in the preceding paragraph. In some embodiments, the composition has an acid value of greater than 190. In other embodiments, the composition has an acid value of from about 190-210. In still other embodiments, the composition is substantially free of esters of conjugated linoleic acid. In further embodiments, the composition comprises less than 1.0% trans-trans fatty acid isomers on molar basis. In some embodiments, food products or capsules comprising the conjugated linoleic acid compositions are provided.
In some embodiments, the present invention provides methods for producing conjugated linoleic acid with a high acid value comprising: a) providing: i) a composition comprising esters of linoleic acid; and ii) an alcoholate catalyst; b) treating the composition comprising esters of linoleic acid with the alcoholate catalyst to produce a conjugated linoleic acid ester composition; c) treating the conjugated linoleic acid ester composition with alkali to produce a saponified conjugated linoleic acid composition comprising residual alcohol; d) removing the ethanol from the saponified conjugated linoleic acid composition; and e) treating the saponified conjugated linoleic acid composition with an acid solution to produce a free conjugated fatty acid composition. In some embodiments, the free conjugated linoleic acid composition has an acid value of greater than 190. In other embodiments, the free conjugated linoleic acid composition has an acid value of from about 190 to 210. In some embodiments, the strong acid solution has a pH of from about 2 to 3. The present invention is not limited to any particular starting oil. Indeed, the composition comprising esters of linoleic acid is derived from an oil selected from the group consisting of safflower, sunflower, and corn oil. The present invention is not limited to the use of any particular alcoholate catalyst. Indeed, the alcoholate catalyst is selected from the group consisting of sodium methylate, potassium methylate, sodium ethylate and potassium ethylate.
In some embodiments, the present invention provides the conjugated linoleic acid composition produced by the method described in the preceding paragraph. In some embodiments, the composition has an acid value of greater than 190. In other embodiments, the composition has an acid value of from about 190-210. In still other embodiments, the composition is substantially free of esters of conjugated linoleic acid. In further embodiments, the composition comprises less than 1.0% trans-trans fatty acid isomers on molar basis. In some embodiments, food products or capsules comprising the conjugated linoleic acid compositions are provided.
As used herein, xe2x80x9cconjugated linoleic acidxe2x80x9d or xe2x80x9cCLAxe2x80x9d refers to any conjugated linoleic acid or octadecadienoic fatty acid. It is intended that this term encompass and indicate all positional and geometric isomers of linoleic acid with two conjugated carbon-carbon double bonds any place in the molecule. CLA differs from ordinary linoleic acid in that ordinary linoleic acid has double bonds at carbon atoms 9 and 12. Examples of CLA include cis- and trans isomers (xe2x80x9cE/Z isomersxe2x80x9d) of the following positional isomers: 2,4-octadecadienoic acid, 4,6-octadecadienoic acid, 6,8-octadecadienoic acid, 7,9-octadecadienoic acid, 8,10-octadecadienoic acid, 9,11-octadecadienoic acid and 10,12 octadecadienoic acid, 11,13 octadecadienoic acid. As used herein, xe2x80x9cCLAxe2x80x9d encompasses a single isomer, a selected mixture of two or more isomers, and a non-selected mixture of isomers obtained from natural sources, as well as synthetic and semisynthetic CLA.
As used herein, the term xe2x80x9cisomerized conjugated linoleic acidxe2x80x9d refers to CLA synthesized by chemical methods (e.g., aqueous alkali isomerization, non-aqueous alkali isomerization, or alkali alcoholate isomerization).
As used herein, the term xe2x80x9cconjugated linoleic acid moietyxe2x80x9d refers to any compound or plurality of compounds containing conjugated linoleic acids or derivatives. Examples include, but are not limited to fatty acids, alkyl esters, and triglycerides of conjugated linoleic acid.
As used herein, it is intended that xe2x80x9ctriglyceridesxe2x80x9d of CLA contain CLA at any or all of three positions (e.g., SN-1, SN-2, or SN-3 positions) on the triglyceride backbone. Accordingly, a triglyceride containing CLA may contain any of the positional and geometric isomers of CLA.
As used herein, it is intended that xe2x80x9cestersxe2x80x9d of CLA include any and all positional and geometric isomers of CLA bound through an ester linkage to an alcohol or any other chemical group, including, but not limited to physiologically acceptable, naturally occurring alcohols (e.g., methanol, ethanol, propanol). Therefore, an ester of CLA or esterified CLA may contain any of the positional and geometric isomers of CLA.
It is intended that xe2x80x9cnon-naturally occurring isomersxe2x80x9d of CLA include, but are not limited to c11,t13; t11,c13; t11,t13; c11,c13; c8,t10; t8,c10; t8,t10; c8,c10; and trans-trans isomers of octadecadienoic acid, and does not include t10,c12 and c9,t11 isomers of octadecadienoic acid. xe2x80x9cNon-naturally occurring isomersxe2x80x9d may also be referred to as xe2x80x9cminor isomersxe2x80x9d of CLA as these isomers are generally produced in low amounts when CLA is synthesized by alkali isomerization.
As used herein, xe2x80x9clow impurityxe2x80x9d CLA refers to CLA compositions, including free fatty acids, alkylesters, and triglycerides, which contain less than 1% total 8,10 octadecadienoic acids, 11,13 octadecadienoic acids, and trans-trans octadecadienoic acids.
As used herein, xe2x80x9ccxe2x80x9d encompasses a chemical bond in the cis orientation, and xe2x80x9ctxe2x80x9d refers to a chemical bond in the trans orientation. If a positional isomer of CLA is designated without a xe2x80x9ccxe2x80x9d or a xe2x80x9ctxe2x80x9d, then that designation includes all four possible isomers. For example, 10,12 octadecadienoic acid encompasses c10,t12; t10,c12; t10,t12; and c10,c12 octadecadienoic acid, while t10,c12 octadecadienoic acid or CLA refers to just the single isomer.
As used herein, the term xe2x80x9coilxe2x80x9d refers to a free flowing liquid containing long chain fatty acids (e.g., CLA), triglycerides, or other long chain hydrocarbon groups. The long chain fatty acids, include, but are not limited to the various isomers of CLA.
As used herein, the term xe2x80x9cphysiologically acceptable carrierxe2x80x9d refers to any carrier or excipient commonly used with oily pharmaceuticals. Such carriers or excipients include, but are not limited to, oils, starch, sucrose and lactose.
As used herein, the term xe2x80x9coral delivery vehiclexe2x80x9d refers to any means of delivering a pharmaceutical orally, including, but not limited to, capsules, pills, tablets and syrups.
As used herein, the term xe2x80x9cfood productxe2x80x9d refers to any food or feed suitable for consumption by humans, non-ruminant animals, or ruminant animals. The xe2x80x9cfood productxe2x80x9d may be a prepared and packaged food (e.g., mayonnaise, salad dressing, bread, or cheese food) or an animal feed (e.g., extruded and pelleted animal feed or coarse mixed feed). xe2x80x9cPrepared food productxe2x80x9d means any pre-packaged food approved for human consumption.
As used herein, the term xe2x80x9cfoodstuffxe2x80x9d refers to any substance fit for human or animal consumption.
As used herein, the term xe2x80x9cvolatile organic compoundxe2x80x9d refers to any carbon-containing compound which exists partially or completely in a gaseous state at a given temperature. Volatile organic compounds may be formed from the oxidation of an organic compound (e.g., CLA). Volatile organic compounds include, but are not limited to pentane, hexane, heptane, 2-butenal, ethanol, 3-methyl butanal, 4-methyl pentanone, hexanal, heptanal, 2-pentyl furan, octanal.
As used herein, the term xe2x80x9cmetal oxidant chelatorxe2x80x9d refers to any antioxidant that chelates metals. Examples include, but are not limited to lecithin and citric acid esters.
As used herein, the term xe2x80x9calcoholate catalystxe2x80x9d refers to alkali metal compounds of any monohydric alcohol, including, but not limited to, potassium methylate and potassium ethylate.
The compositions of the present invention result from a highly controlled isomerization process, and from using the preferred starting materials of sunflower, safflower, or corn oil. This composition has not heretofore been obtained, for application to an industrial scale, because the conventional processes historically produce conjugated linoleic acids for entirely different purposes, namely, as drying oils in the paint industry. Also, there has not been an appreciation of the implications of the isomer content of the final product, because the analytical methods for characterizing the fatty acids has not been widely available. Furthermore, the present invention provides a method for preventing oxidation of CLA during storage to form volatile organic compounds.
In the older isomerization processes, some of which are still in use in more modern format, production of the conjugated fatty acids was carried out in aqueous alkali (generally NaOH) at high temperatures in excess of 200xc2x0 C. and usually at superatmospheric pressures. For example, U.S. Pat. No. 2,350,583 (Bradley) discloses an aqueous alkali process utilizing treated soaps in which both conjugation and polymerization occurred under rather harsh conditions at 200 to 250xc2x0 C. for a period of several hours. The fractions of drying oil, starting with linseed oil, were obtained by distillation (see also Br. Pat. No. 558,881 for a very similar process). In a variation of the process, U.S. Pat. No. 4,381,264 teaches a process where a low water content reaction zone (0.5% water) contains stoichiometric base in the presence of SO2 to obtain conjugation of the double bonds of various polyunsaturated fatty acids. The aqueous alkali process was adapted in U.S. Pat. No. 4,164,505 to a continuous flow process in which an alkali metal hydroxide and water are continuously charged in a flow zone maintained at between 200 and 370xc2x0 C. At these temperatures, the time of reaction should be greatly foreshortened, but there is relatively little control over the isomerization. At the higher end of the temperature range, one skilled in the art would predict almost complete conversion to double trans species.
Methods of producing CLA using various nonaqueous solvents and catalysts have been described in the literature. Burr (U.S. Pat. No. 2,242,230) discloses the use of solvents such as methanol, butanol, ethanol and glycol in combination with various catalysts. These reaction parameters are summarized in Table 1. With the exception of glycol, the reactions were conducted either under reflux conditions or in sealed tubes. These reaction conditions result in imprecise control of two of the important reactions parameters-temperature and pressure. Imprecise control of these reactions parameters is likely to lead to less than complete conjugation and the formation of undesirable isomers.
Likewise, Baltes et al., (U.S. Pat. No. 3,162,658) disclose the use of nonaqueous solvents and various metallic bases as catalysts for the conjugation of fatty acids. The various reaction parameters of the methods described by Baltes et al. are summarized in Table 2. Baltes et al. also disclose the use of various low boiling point solvents. As most of these reactions were conducted at temperatures above the boiling point of the solvent employed, it is apparent that the reactions were conducted under pressure, which is an independent factor influencing the formation of octadecadienoic acid isomers. The product derived from these reactions will thus contain undesirable isomers.
The CLA of the present invention lacks significant amounts of isomers such as the 8,10 isomer, the 11,13 isomer, and the various trans-trans isomers. These compositions were produced by a tightly controlled nonaqueous alkali isomerization process presented in flow diagram form in FIG. 1 and by isomerization with alkali alcoholate catalysts.
In preferred embodiments, esters of linoleic acid derived from sunflower oil, safflower oil, or corn oil are reacted in the presence of an alkali alcoholate catalyst and a small amount of a suitable solvent (e.g., methanol or ethanol). Accordingly, the present invention provides methods for producing alkyl esters of CLA. After fat splitting and dehydration of the seed oil, the free fatty acids are combined with methanol or another monohydric low molecular weight alcohol and heated to the temperature at which the alcohol boils. Esterification proceeds under refluxing conditions with removal of the reaction water through a condenser. The seed oil is refluxed with an excessive amount of alcohol and an alkali alcoholate catalyst for 2 hours at 65-78xc2x0 C. while stirring. After separation of the layers, the bottom layer containing glycerol and excess alcohol is decanted. The esterification process can then be repeated with a smaller amount of alcohol and an alkali alcoholate catalyst to get an even more complete esterification. The ester is then washed with hot water with dissolved citric acid and dried under vacuum. In preferred embodiments, the esters are distilled prior to conjugation to remove glycerol and prevent formation of trimethoxypropane. Accordingly, the conjugated linoleic acid compositions of the present invention are substantially free of trimethoxypropane. By substantially free of trimethoxypropane it is meant that the final product contains less than 0.5% trimethoxypropane, more preferably less than 0.1% trimethoxypropane, and most preferably less than 0.05% trimethoxypropane.
In the esterification, methanol or ethanol are preferred, although other branched or straight chain monohydric alcohols may be used. The longer the aliphatic chain of the alkyl group, the more lipid compatible the material becomes. Also the viscosity tends to increase. For different types of feed or food, whose consistency varies, products of varying viscosity can be used to obtain the desired flow or compounding characteristics without affecting the therapeutic or nutritional properties arising from the CLA moieties. The theory and practice of esterification are conventional. A basic explanation of the most common methods is set forth in the McGraw-Hill Encyclopedia of Science and Technology, McGraw-Hill Book Co., N.Y.: 1996 (5th ed.). The animal and human body has a variety of esterases, so that the CLA-ester is cleaved to release the free fatty acids readily. Tissue uptake may have a different kinetics depending on the tissue involved and the benefit sought.
As described above, the preferred starting materials for conjugation with alcoholate catalysts are esters of linoleic acid derived from sunflower oil, safflower oil, and corn oil or other oils with a high linoleic acid content. Preferably the oils contain low levels of linolenic acid. Conjugation of linolenic acid results in the formation of several uncharacterized fatty acid moieties, the biological properties of which are unknown. Previous conjugation processes were not concerned with the production of unknown compounds because the products were used in drying oils, paints and varnishes and not in products destined from human or animal consumption. Accordingly, the CLA produced by those processes with oils containing high levels of linolenic acid were not suitable for nutritional uses.
In some embodiments, it is further contemplated that glycerol and esters of glycerol should be removed before making monoesters of fatty acids. Traces of glycerol present during conjugation contribute to the production of trimethoxypropane and triethoxypropane. Therefore, prior to conjugation, it is preferable to distill monoesters obtained by alcoholysis.
In preferred embodiments, isomerization is accomplished by reacting the esters of linoleic acid with a quantity of a monohydric alcohol (e.g., methanol, ethanol, propanol, or butanol) and an alcoholate catalyst (See, e.g., U.S. Pat. No. 3,162,658, incorporated herein by reference). Typical alcoholate catalysts are sodium or potassium ethoxide, or their methyl, butyl, or propyl counterparts (e.g., sodium methylate, potassium methylate, sodium ethylate and potassium ethylate). In some embodiments, the ratios of alcoholate catalyst and alcohol to the fatty acid esters is approximately 2-5% on a weight/weight basis, most preferably the ratios of alcoholate catalyst and alcohol to the fatty acid esters is about 2.8% on a weight/weight basis. For example, 100 kg of safflower fatty acid esters are mixed with 2.8 kg potassium ethoxide and 2.8 kg ethanol. In some embodiments, the resulting reaction mixture is stirred for about 2-10 hours, most preferably about 5 hours, at 100 to 130xc2x0 C., most preferably at about 111-115xc2x0 C. In some preferred embodiments, the reaction is conducted in a closed reaction vessel under nitrogen. This isomerization reaction produces conjugated linoleic acid alkyl esters.
In some preferred embodiments, the conjugated linoleic acid alkyl esters are converted to free fatty acids (i.e., free conjugated fatty acids). This is preferably accomplished by first saponifying the conjugated linoleic acid alkyl esters to produce a soap of conjugated linoleic acid and then splitting the soap by addition of an acid. In some embodiments, saponification is performed by reacting the alkyl esters of conjugated linoleic acid with an appropriate base. The present invention is not limited to the use of any particular base. Indeed, a variety of bases may be utilized, including, but not limited to, NaOH and KOH. Likewise, the present invention is not limited to the use of any particular acid. Indeed, a variety of acids may be utilized, including, but not limited to HCl, citric acid, and acetic acid.
The inventors unexpectedly discovered that during saponification and subsequent addition of acid to produce free fatty acids from a conjugated alkylester, the reverse reaction took place. Under certain circumstances, residual amounts of alcohol generated from the saponification of the alkylester (e.g., methanol or ethanol) react with the free fatty acids under acid conditions to produce esters (e.g., ethyl or methyl esters) of CLA. This results in a final product with an unacceptably low acid value. It is well known for those skilled in the art that esterification occurs between free fatty acids and alcohol if strong acids are used as catalysts. However, taking into account the low content of ethanol, an esterification was not expected to occur. The reason is probably that addition of acidic water does not remove ethanol from the free fatty acids layer as expected. CLA does probably due to polarity in the double bond region dissolve ethanol more easily than other fatty acids.
The present invention contemplates that the addition of several mild acid wash steps to the methods of CLA production using the isomerization with alcoholate catalysts disclosed herein is particularly useful in the batch production of CLA. Preferred embodiments of the present invention overcome the unexpected accumulation of esters (e.g., methyl esters or ethyl esters) of CLA during isomerization with alcoholate catalysts, by utilizing a plurality of (e.g., 1, 2, 3, or more) mild acid washes following the isomerization and saponification steps to ensure the removal of residual ethanol from the reaction mixture. It is contemplated that removal of residual amounts of ethanol prevents esterification reactions from taking place that produce ethyl ester derivatives of CLA. Preferably, the pH of the reaction mixture during the mild acid washes of the saponified CLA is kept from about 5 to 7. Suitable acids for use in the mild acid wash step include, but are not limited to, citric acid monohydrate, citric acid, or mild organic acids like acetic acid. The acids are mixed with a solvent (e.g., water) to produce a wash solution with a pH from about 5 to 7.
Examples 2 and 3 provide exemplary embodiments related to the mild acid washing steps described above. In particular, Example 2 describes the problem of ethyl ester production at batch scale production levels in certain embodiments of the alcoholate catalysts isomerization methods. Example 3 describes the addition of mild acid washing steps following isomerization and saponification steps in the alcoholate catalyst production methods at batch scale production levels.
In some embodiments, an in-line process may be used for soap splitting instead of a batch process. In these embodiments, a CLA soap stream is passed from a batch reactor into an inline reaction chamber for addition of a diluted acid solution (preferably having a pH of from about 2 to 3). A high speed mixer is used to split the CLA soap into free fatty acids. Small amounts of soap could potentially facilitate formation of an emulsion. Therefore, in addition to high speed mixing with the dilute acid, the temperature should preferably be maintained at about 80 to 90xc2x0 C. From the acid addition reaction chamber, a stream containing the oil and water phases is immediately passed (e.g., within less than about 20 seconds after acid addition) into a centrifugal separator, where the oil and water are separated. The oil preferably contains a small amount of water at this stage in order to minimize loss of oil in the water phase. The temperature at this stage should still be maintained at from about 80 to 90xc2x0 C. to facilitate rapid and complete splitting of the soap and to minimize emulsion problems.
In other alternative embodiments, the saponified CLA may be hydrolyzed enzymatically. Preferred enzymes include, but are not limited to, Novozym 435 and any other enzyme that is non-specific for triacylglycerol synthesis or hydrolysis (i.e., esterifies/hydrolyze all hydroxygroups (sn-1,sn-2 and sn-3) of glycerol). In still other alternative embodiments, the re-esterification reaction is substantially prevented by removing residual ethanol prior to treatment with acid. In preferred embodiments, the ethanol is removed from the soap by vacuum suction.
The compositions resulting from the processes described above may have a slightly yellow color due to residual soap and the presence of dimers. Accordingly, in some preferred embodiments, the resulting conjugated fatty acid composition is distilled to remove any impurities. In preferred embodiments, the finally product is essentially colorless and substantially free of contaminants such as dimmers or soaps. In preferred embodiments, the conjugated fatty acid compositions contain less then 10 ppm soap and/or less than 0.1% dimmers on a weight/weight basis as compared to conjugated fatty acid content. In preferred embodiments, the acid value of the final CLA composition produced by the methods described above is greater than 190, preferably ranging from about 190 to 210. Furthermore, the final product is substantially free of esters of CLA. By substantially free, it is meant that the concentration of ethyl esters CLA is less than about 1.0% of the concentration of free conjugated linoleic acid on a molar basis, and preferably less than 0.5% of the concentration of free conjugated linoleic acid on a molar basis. In preferred embodiments, the resulting composition contains less than 1.0% trans-trans fatty acids as compared to other fatty acids on a molar basis, and preferably less than 0.5% trans-trans fatty acids as compared to other fatty acids on a molar basis.
The free conjugated linoleic acids produced by these methods are suitable for a variety of uses. For example, the CLA may be used a dietary supplement, incorporated into food products, or formulated for oral delivery as described in more detail below. The CLA may also be utilized for the production of acylglycerols, preferably diacylglycerols of triacylglycerols, for oral administration or incorporation into food products or powders.
The present invention also contemplates stabilization of CLA containing compounds, including but not limited to, CLA, esters of CLA, and triglycerides of CLA by preventing oxidation of the compounds. The present invention is not limited to any one mechanism. Indeed, an understanding of the mechanism of the invention is not necessary to produce the composition or perform the methods of the present invention. Nevertheless, unlike non-conjugated fatty acids, CLA does not appear to form peroxide breakdown products. This was demonstrated experimentally by measuring peroxide values (PV) spectrophotometrically by a chlorimetric ferric thiocyanate method. After storage in open glass, the PV of CLA was 32; in comparison, the value for linoleic acid was 370.
CLA forms volatile organic compounds during breakdown, including hexane. Products stored in a steel drum for several weeks were found to contain up to 25 ppm hexane. Hexane has a characteristic taste and smell that is undesirable in food products. Oxidation of CLA appears to be caused by the presence of metal contaminants. Thus, a system for removal of such compounds that promote oxidation during purification is advantageous.
Furthermore, it is also advantageous to add compounds to CLA preparations to decrease oxidation during storage. Compounds that prevent oxidation (antioxidants) have two general mechanisms of action. The first is the prevention of oxidation by lipid peroxide radical scavenging. Examples include but are not limited to tocopherols and ascorbylpalmitate. The second mechanism for preventing oxidation is by the chelation of metal ions. Examples of metal oxidant chelators include, but are not limited to, citric acid esters and lecithin. Some commercially available compounds (e.g., Controx, Grunau (Henkel), Illertissen, Del.) include both peroxide scavengers and metal chelators (e.g., lecithin, tocopherols, ascorbylpalmitate, and citric acid esters). In some embodiments of the present invention, metal oxidant chelators are added to CLA containing compounds to prevent oxidation. In other embodiments, a combination of metal oxidant chelators and peroxide scavengers is included in the CLA composition.
In some embodiments, gas chromatography/mass spectroscopy is used in detect the presence of volatile organic breakdown products of CLA. In other embodiments, oil stability index (OSI) measurements are used to detect the presence of volatile organic breakdown products of CLA. In some embodiments of the present invention methods for the removal of pro-oxidants (e.g., iron) from CLA samples are provided. Methods include, but are not limited to distillation or by adsorption. In some embodiments of the present invention, compounds are added to prevent oxidation of CLA. Examples of volatile organic compounds include pentane, hexane, heptane, 2-butenal, ethanol, 3-methyl butanal, 4-methyl pentanone, hexanal, heptanal, 2-pentyl furan, and octanal. It is understood by one skilled in the art that samples may contain additional volatile organic compounds, depending on the starting materials and the exact reaction conditions.
In preferred embodiments, precautions are taken during purification to prevent oxidation during storage. These precautions include the removal of compounds that serve as pro-oxidants, including but not limited to iron or other metals. In some embodiments, metals are removed by treating with adsorbing agents, including but not limited to bleaching earth, active charcoal zeolites, and silica. In other embodiments, the pro-oxidants are removed by distillation. In some embodiments, silica is used as the adsorbing agent. In other embodiments, pro-oxidants are removed in a distillation process. In some embodiments, oxidation of CLA is prevented by the addition of metal oxidant chelators or peroxide scavengers to the finished product. In some embodiments, the amount of oxidation is measured by the oil stability index (OSI). The OSI (See e.g., AOCS official method Cd 12b-92) is a measurement of an oil""s resistance to oxidation. It is defined mathematically as the time of maximum change of the rate of oxidation. This rate can be determined mathematically. Experimentally, the OSI is calculated by measuring the change in conductivity of deionized water is which volatile organic acids (oxidation products) are dissolved. When performing OSI measurements, it is important to avoid contamination by trace amounts of metals, which can accelerate the oxidation process. This is generally accomplished by careful washing of all glassware used with a cleaning solution lacking chromate or surfactants. Water must be deionized and all solvents must be of a highly purified grade.
The conjugated linoleic moieties of the present invention may be provided in a variety of forms. In some embodiments, administration is oral. The CLA moieties may be formulated with suitable carriers such as starch, sucrose or lactose in tablets, pills, dragees, capsules, solutions, liquids, slurries, suspensions and emulsions. Preferably, the CLA formulations contain antioxidants, including, but not limited to Controx, Covi-OX, lecithin, and oil soluble forms of vitamin C (ascorbyl palmitate). The CLA may be provided in aqueous solution, oily solution, or in any of the other forms discussed above. The tablet or capsule of the present invention may be coated with an enteric coating which dissolves at a pH of about 6.0 to 7.0. A suitable enteric coating which dissolves in the small intestine but not in the stomach is cellulose acetate phthalate. In some embodiments, the CLA is provided as soft gelatin capsules containing about 750 mg CLA. The CLA may also be provided by any of a number of other routes, including, but not limited to, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual or rectal means. Further details on techniques for formulation for and administration and administration may be found in the latest edition of Remington""s Pharmaceutical Sciences (Maack Publishing Co., Easton, Pa.).
An effective amount of a CLA moiety (in free fatty acid, alkyl ester, or acylglycerol form) may also be provided as a supplement in various food products, including animal feeds, and drinks. For the purposes of this application, food products containing CLA means any natural, processed, diet or non-diet food product to which exogenous CLA has been added. The CLA may be added in the form of free fatty acids, esters of conjugated linoleic acid, or as an oil containing partial or whole triglycerides of CLA. Therefore, CLA may be directly incorporated into various prepared food products, including, but not limited to diet drinks, diet bars, supplements, prepared frozen meals, candy, snack products (e.g., chips), prepared meat products, milk, cheese, yogurt and any other fat or oil containing foods. Food products formulated with alkyl esters or conjugated linoleic acid moieties produced by alkali alcoholate catalysts contain alcohols (e.g., methyl or ethyl alcohol) depending on the solvents and catalysts utilized. Generally, the alcohols will be present at about 1 to 10 ppm.
Furthermore, as shown above and in the Examples, CLA compositions can contain levels of volatile organic compounds that cause the taste and smell of food products containing the CLA to be adversely effected. It is contemplated that the food products of the present invention that contain CLA compositions having less than 100 ppm volatile organic compounds, and preferably less than 5 ppm volatile organic compounds, are superior in taste and smell to food products containing higher levels of volatile organic compounds and will be preferred in blind taste and smell tests. Accordingly, some embodiments of the present invention provide a food product containing a conjugated linoleic acid moiety, wherein the conjugated linoleic acid moiety has a sufficiently low volatile organic acid compound concentration so that taste and smell of the food product is not affected.


The present invention relates to nonionic compounds of the polyoxymethylene type that are low-foaming and can be used as surfactants, especially in cleaning compositions at an alkaline pH. They are obtained from unsaturated nitriles, that have been epoxidized with e.g. hydrogen perroxide, and alkyl blocked polyalkylene glycols. The nonionic nitrile surfactants can be reacted further with e.g. hydrogen peroxide under alkaline conditions to obtain nonionic amide surfactants. Amide derivatives of this type could also be obtained by reaction between ammonia or a primary or secondary amine and an acid or ester. The nonionic compounds exhibit one or several structure elements according to formula (II)

The present application was filed on Jun. 19, 2000 as international application serial number PCT/SE00/01285 and claims priority of Swedish patent application No. 99002450-7 filed on Jun. 29, 1999.
The present invention relates to nonionic compounds of the polyoxyalkylene type that are low-foaming and can be used as surfactants, especially in cleaning compositions at an alkaline pH. They are obtainable from unsaturated nitriles, that have been epoxidised with e.g. hydrogen peroxide, and alkyl blocked polyalkylene glycols. The nitrile surfactants can be reacted further with e.g. hydrogen peroxide under alkaline conditions to obtain amides. Amide derivatives of this type can also be obtained from unsaturated acids or esters that have been epoxidised and thereafter reacted with alkyl blocked polyalkylene glycols. These acid or ester derivatives are transformed to the corresponding amide derivatives by reaction with ammonia or a primary or secondary amine.
Nonionic surfactants constitute an important group of surface-active compounds that are widely used in numerous applications. However, many of the ethylene oxide adducts containing a hydrophobic chain with 12-22 carbon atoms are too high-foaming to be used in certain applications, such as e.g. machine dish-washing, machine washing of textiles, bottle cleaning and cleaning of hard surfaces.
It has been suggested in EP-A2-0 754 667 to produce new nonionic surfactants, that would generate less foam, by reacting an epoxidised fatty acid ester with a polyglycol ether. These ring-opened products are claimed to be particularly suited to be used as defoamers in a variety of applications. In WO 94/07840 similar products are obtained by reacting epoxidised esters with fatty alcohol polyglycol ethers. These products are claimed to be low-foaming and to have a good biodegradability, and are used as auxiliaries in the removal of water from solid materials.
However, there is a drawback when using the ester polyglycol ether compounds, since the ester group is readily hydrolysed when subjected to highly alkaline conditions. This excludes applications where a high pH is required, since the nonionic product would then be converted to an anionic product.
Nonionic products containing a cyano group, which is a more stable functional group than the ester group, have been described by Wrigley, Smith and Stirton (J. Am. Oil Chem. Soc. 39:80-84 (1962)). These surfactants were obtained by treatment of an unsaturated nitrile with 98% formic acid and 30% hydrogen peroxide to give the hydroxy-formate, followed by mild hydrolysis to yield the dihydroxy compound, which was then ethoxylated using KOH as a catalyst. However, since both the hydroxyl groups of the intermediate product are secondary, the final product will not be very-well defined. Once an ethylene oxide unit has been attached to the secondary hydroxyl group, there will be a primary hydroxyl group present, which will add another ethylene oxide unit much faster than the remaining secondary groups. The end result will be a product where one of the polyoxyethylene chains is much longer than the other, a lot of the polyoxyethylene homologues will probably contain only short chains, and some part of the hydrophobic diol will even be unreacted. Thus, in the above-mentioned article it is stated that ethoxylation of 9,10-dihydroxystearonitrile with 4 moles of ethylene oxide leaves 5.9% of starting diol.
Consequently there is a need for low-foaming products that are more stable than the prior known ester polyglycol ethers and better defined than the ethoxylated diol nitriles. The purpose of the present invention is to provide such products.
It has now been found that these objectives can be met by a new class of low-foaming well-defined compounds, which can easily be prepared from starting materials that are easy to handle and that can be obtained by standard procedures, by reacting an epoxidised nitrile with an alkyl blocked polyalkylene glycol. Since the compounds that are obtained are low-foaming, they are suitable to use e.g. in cleaning compositions for applications where low foam is required, such as vehicle cleaning, bottle cleaning and machine-washing. To obtain products with even better toxicological and environmental profiles that still are relatively stable, the nitrile group can be converted to an amide group by treatment with e.g. alkaline hydrogen peroxide. An amide derivative according to the invention could also be produced by the reaction between an acid or ester derivative of the type described in EP-A2-0 754 667 and ammonia or a primary or secondary amine.
The nonionic compounds according to the present invention are characterised by the general formula RY (I), where R is a substituted aliphatic group containing 1-3 structure elements with the formula
where the carbon atoms shown in the structure element are part of the aliphatic carbon skeleton of group R, which. contains 8-24 carbon atoms, preferably 12-22 carbon atoms, and Y is a nitrile or an amide group; R3 is an alkyl group with 1-4 carbon atoms; AO is an alkyleneoxy group containing 2-4 carbon atoms and n is a number between 1 and 30, preferably 3-20. The number of structure elements contained in the chain is preferably 1-2.
Suitable examples of the above-mentioned compounds are those having the formulae
where R1 is an aliphatic group, R2 is an aliphatic radical, the sum of carbon atoms contained in R1 and R2 is between 9 and 19 and R3, AO, n and Y have the same meaning as above.
Suitable amide groups are those having the formula
where R4 and R5 independently are H, an alkyl group with 1-6 carbon atoms, preferably 1-4 carbon atoms, or (AO)m where AO is an alkyleneoxy group containing 2-3 carbon atoms, preferably 2, and m is 1-20, preferably 1-2. Most preferably at least one of R4 and R5 is H.
The nonionic compounds according to the invention may be produced by
a) reacting an epoxidised nitrile containing 1-3 epoxy groups and a total of 8 to 24 carbon atoms, preferably 12-22 carbon atoms, with an alkyl blocked polyalkylene glycol having the formula R3O(AO)nH, where R3, AO and n has the same meaning as in formula II, in the presence of a catalyst, and optionally subjecting the product obtained to alkaline hydrogen peroxide or
b) reacting ammonia or a primary or secondary amine with an acid or an ester containing 1-3 structure elements according to formula II in the aliphatic skeleton. The alkyleneoxy groups could be distributed randomly or in blocks or a mixture thereof. Normally at least 50% of the alkyleneoxy groups are ethyleneoxy groups. Alkyl blocked polyethylene glycols are the reactants most often used. Suitable examples of alkyl blocked polyalkylene glycols are CH3(CH2CH(CH3)O)2(CH2CH2O)10R and CH3(CH2CH2O)14H.
When the reaction between a monoepoxidised nitrile and the alkyl blocked polyalkylene glycol takes place, there is an equal chance for attack by the glycol on either of the two carbons in the epoxy ring. Consequently two regioisomers are formed in about the same amount, as is shown by formula IIIa and IIIb.
The epoxidised nitrites could be derived from unsaturated nitriles e.g. by using the Venturello method described in GB-A-2055821, where hydrogen peroxide is used as the source of active oxygen, or by the use of peracids. The unsaturated nitriles could contain more than one double bond, and the epoxidation of such polyunsaturated nitriles can consequently give rise to products containing more than one epoxy group. Accordingly, the nonionic compounds derived from such polyepoxidised nitrites could contain several polyoxyethylene chains distributed along the aliphatic skeleton. Naturally occurring fatty acids, which are the starting material for the nitrites, are normally mixtures between acids with different amounts of double bonds, and consequently the resulting end products will also be mixtures of compounds containing different numbers of polyoxyethylene chains.
The unsaturated nitriles are intermediates in the process for the manufacturing of fatty amines, and they are thus readily available in large quantities. Oleonitrile is a suitable example of an unsaturated nitrile, but also other nitrites derived from unsaturated acids would be possible to use. Examples of such acids are tall oil acid, linoleic acid, erucic acid and fish-oil acids, as well as unsaturated synthetic acids.
The reaction between the epoxynitriles and the alkyl blocked polyalkylene glycols could be catalysed both by acids, such as Lewis acids e.g. BF3, and by alkali, such as alkoxides.
The conversion of the nitrile group to an amide group by the treatment with alkaline peroxide is described e.g. in Organic Synthesis Collective Vol. II p. 586.
The nonionic amide compounds according to the invention could also be obtained by a standard procedure via the suitable acid or ester derivatives by reaction with ammonia or an amine. Suitable examples of amines are primary or secondary alkylamines, ethanolamine and diethanolamine.
The following examples are illustrative of the invention and are not to be construed as limiting thereof.

Compounds from epoxidised nitriles, process for their production and use as cleaning agents

Abstract: in the aliphatic carbon chain where AO is an alkyleneoxy group containing 2-4 carbon atom, R3 is an alkyl group with 1-4 carbon atoms and n is a number between 1 and 30.


Systems and methods are disclosed to receive an image depicting at least a part of a document and identify a plurality of partition points dividing the image into potential segments; generate a linear partition graph (LPG) comprising a plurality of vertices using the plurality of partition points and a plurality of arcs connecting the plurality of vertices; identify a path of the LPG having a value of a quality metric above a threshold value, wherein the path is selected from a plurality of paths of the LPG and comprises one or more arcs and the value of the quality metric is derived using a neural network classifying each of a plurality of pixels of the image; and generate one or more blocks of the image wherein each of the one or more blocks corresponds to an arc of the identified path and represents a portion of the image associated with a type of an object.

An image may depict a document or a part of a document. The document may consist of various types of segments or blocks, such as title blocks, text blocks, chart blocks, table blocks, etc. An image processing engine may be tasked with identifying blocks of various types within an image.

Methods and systems of segmentation of a document


Provided is an avoidance maneuver calculation device that calculates a driving maneuver amount that enables an automotive vehicle to avoid an obstacle within a travelable range of a road. The device includes: a road boundary detector for detecting a road 13 where a vehicle 12 is traveling and a boundary section thereof; an obstacle detector for detecting an obstacle 14 existing on the road 13; an automotive vehicle information detector for detecting information on the vehicle 12; and an avoidance maneuver calculator 28 for calculating a maneuver amount for avoiding the obstacle 14 on the road 13.

A conventional traveling safety device is configured to detect an obstacle on a road where an automotive vehicle is traveling and to maneuver the automotive vehicle by driving an actuator for electric power steering upon detection of the obstacle. Thereby, the automotive vehicle avoids the obstacle. When trying to avoid an obstacle, this traveling safety device deflects a traveling direction of the automotive vehicle from a direction of the road, i.e. the direction along a track shape of the road. Accordingly, a driver needs to perform steering to bring the traveling direction of the automotive vehicle back to the direction of the road. This steering is burdensome to the driver. Moreover, the driver experiences a discomfort as the traveling direction of the automotive vehicle deviates from the direction of the road.
For this reason, JP-A 2001-1925 (pp. 2 to 18, FIG. 5) discloses a traveling safety device configured to perform the steering so as to align a traveling direction of an automotive vehicle with a direction of a road upon a judgment that an obstacle is avoided. This traveling safety device aligns the traveling direction of the automotive vehicle, which is deviated from the direction of the road, with the direction of the road again after the automotive vehicle avoids the obstacle. Accordingly, it is possible to reduce a burden and a discomfort for a driver, as compared to the case of only performing avoidance maneuver.

Avoidance maneuver calculation device, avoidance control device, vehicle having each device, avoidance maneuver calculating method, and avoidance controlling method


A semiconductor device includes a package 1, a block-module 2, and a control board 3 for controlling power semiconductor elements 11a. The block-module 2 has embedded power semiconductor elements 11a and second leads 4b and first leads 4a that are drawn from the block-module 2. The package 1 has external connection terminals 6a in contact with the first leads 4a of the block-module 2. The second leads 4b are connected to the control board 3 while the first leads 4a are joined to the external connection terminals 6a.

A semiconductor device (power device) is used for rotation control of a power conditioner or a motor in a photovoltaic power generation system. In order to reduce a footprint, shorten a distance between semiconductor elements to obtain higher performance, and reduce a design load for a user in such a semiconductor device, products (packaged semiconductor devices) including package modules have been increasingly used (for example, see Patent Literatures 1 to 3), the package module containing multiple power devices.
A packaged semiconductor device is called a power module. The power module contains a plurality of power semiconductor elements, e.g., IGBTs (insulated gate bipolar transistors) for switching or MOSFETs (Metal-Oxide-Semiconductor Field Effect Transistors). The power module further contains a plurality of driver elements for driving the power semiconductor elements and a plurality of passive elements. Power modules capable of driving and protecting power semiconductors are particularly called IPMs (Intelligent Power Modules) and have been increasingly available on the market.
As illustrated in FIG. 22, a resin case 102 having an insert-molded metal terminal 101 is used in a conventional semiconductor device. Moreover, a metal plate 103 mainly composed of Cu is attached to the bottom of the resin case 102 with an adhesive 104.
An insulating substrate 105 is joined onto the metal plate 103 with solder 106a and has a wiring pattern including ceramic front and back sides coated with Cu foil. The ceramic is, for example, aluminum oxide (Al2O3) or aluminum nitride (AlN).
Power semiconductor elements 107, e.g., IGBTs or reflux diodes are bonded onto the insulating substrate 105 with solder 106b. An electrode formed on the surface of the power semiconductor element 107 and a relay electrode 108 on the resin case 102 are connected to each other via an aluminum wire 109.
Furthermore, a control board 112 is disposed directly above the power semiconductor element 107. The control board 112 has a control element 110 for controlling the power semiconductor elements 107 and so on and a passive component 111, e.g., a capacitor or a resistor. Pin holes 115 on the control board 112 are inserted onto the relay electrodes 108, electrically connecting the power semiconductor elements 107 and the control element 110.
For protection from an external environment, the power semiconductor elements 107 are molded with silicone gel 113 that is charged into a recessed part 114 of the resin case 102.

Semiconductor device and method of manufacturing the same

Panasonic Intellectual Property Management Co., Ltd.


Systems and methods for the identification, powering and control of products and product packaging. The systems can include a point of sale display having a contactless power supply. The contactless power supply can provide a source of wireless power for products and product packaging. The products and product packaging can include light emitting diodes, e-ink displays and printed speaker circuits that activate as the operating frequency of the contactless power supply varies. Other embodiments include product level sensors, inductive reader networks, printed temperature sensors, product alignment systems, passive identification circuits and methods for controlling operation of the same.

The present invention relates to inductive systems and methods at the point of sale and in other locations.
Point of sale systems can generally include a series of shelving units and associated signage. Gondola shelving units, for example, benefit from being inexpensive, reconfigurable, and capable of displaying a variety of products. Signage can include source information, product information and/or sale information to promote or otherwise draw attention to a corresponding product. For example, signage can include placards affixed to or placed proximate the corresponding shelving unit.
Point of sale systems have also benefited from recent improvements in product packaging. Contemporary product packaging increasingly utilizes RFID labels as one aspect of inventory control, anti-counterfeiting and/or tamper-proofing measures. Product packaging can also serve more traditional functions, including providing a secure housing for a product while also displaying product specifications, compatibility information, power requirements, and hardware requirements.
In addition, point of sale systems can include a network of check-out terminals to monitor product inventory. For example, known inventory control systems include a network of terminals having magnetic stripe readers, bar code readers, check acceptance systems and/or fraud detection systems. Such inventory control systems can automatically reorder a product when the store inventory falls below a given level or in anticipation of an increase in product demand.
While the aforementioned point of sale systems are widely accepted, they suffer from a number of shortcomings. For example, the ability to interact with the product is limited in many display and packaging designs. In addition, losses in battery charge can occur, particularly where a product remains in inventory for an extended period. The visual inspection of product quantities can also become necessary at the point of sale, as inventory control typically occurs at check-out, but not before.
Accordingly, there remains a continued need for improved systems and methods for promoting products and product information at the point of sale. In addition, there remains a continual need for improved systems and methods to leverage the benefits of existing inventory control systems and to improve product identification and automatic reordering at the point of sale, at home, and in other locations.

Point of sale inductive systems and methods


Various embodiments enable an application on a first device to log into an online meeting in association with a trusted entity, such as a trusted user. Once trust is established between the trusted entity and the meeting domain, such as an enterprise domain, permissions can be assigned to a meeting device, by virtue of the trust relationship with the trusted entity, to enable the meeting device to join the meeting as a participant, thus allowing the meeting device to bypass an initial join process such as a meeting lobby and the like. By virtue of the assigned permissions, the meeting device may take control of the meeting and control the experience for others in the meeting as a meeting organizer or some other permission-centric role.

Online meetings have become increasingly more popular in the last several years. Online meetings enable people at different locations to meet and collaborate in a high-quality meeting experience. As technology associated with online meetings evolves, challenges continue to be posed to continue to improve the manner in which online meetings can be conducted and the user experience. For example, challenges continue to be posed to enable meeting rooms and meeting devices to easily join online meetings.


A system includes a transmit unit to transmit a signal including a data key, and a receiving unit to receive the signal. The receiving unit to determine an encryption key based at least in part on the data key and to decrypt encrypted data using the encryption key.

An increasing problem is that of maintaining privacy of equipment, data and personnel. Laws, such as that required by the California Information Act that affects institutions across the country having offices or that do business in California, and Federal Privacy Laws, are adding a much higher level of responsibly and significant financial risk.
Critical organizations have sensitive personnel files and data that include credit card companies, banks, mortgage companies, accounting firms, law firms, hospitals, governments, homeland defense, military, and many others. While a lot of attention has been given to external threats, often, a greater risk is employee theft or even unintentional disclosure.
Recently, the personal files of 26.5 million veterans were improperly taken home by a VA employee, and the files, including social security numbers and other very sensitive veteran's personnel records, were subsequently stolen in a break-in of his house. Before that, the military in Iraq had numbers of critical flash drives, computers and storage mediums stolen by local employees and then sold in flea markets. Banks, credit card and data storage companies have recently had large thefts of personal credit, account records and other data that later was used for identity and credit card theft.
Whether intentional or not, failure to follow privacy laws may be extremity expensive. State laws and liability associated with exposure of private data may lead to fines and costly litigation. As such, an improved method of protecting data would be desirable.

Location-based security, privacy, access control and monitoring system


In the present disclosure, systems and methods are described for video gaming in a controlled environment facility. A video game server allows tenants of a controlled environment facility to play video games that are served and monitored by the video game server. In embodiments, users may initiate a game session to play games in a single player mode, competitive multiplayer or cooperative multiplayer mode depending on the game being played. The video game server maintains block lists for each user such that those users may not initiate or engage in the same game sessions with each other. In game sessions with two or more users, the video game server allows users to communicate via audio or text communications. The video game server may monitor those communications for potential security concerns. Users may also view videos of previously completed or live game sessions, subject to similar security monitoring measures.

Video games have become as ubiquitous and profitable as the film industry in recent years. Globally, in 2014 the gaming industry is estimated to have produced 83.6 billion dollars in revenue, dwarfing global film box office receipts by nearly 50 billion dollars. In 2015, 155 million of the U.S. population was found to play at least some form of video games, with ˜80% out of every five households containing at least one device that can be used to play video games, and 51% of all households owning a dedicated game console such as an Xbox or Playstation console. Video games have also been found to have potential therapeutic effects in a variety of environments. Finally, video game spectating, wherein people view either live broadcasts or on-demand replays of video game sessions, has also exploded in the last decade.
In the context of controlled environment facilities, such as correctional facilities, video gaming has huge potential to impact the lives of the tenants within those environments. However, many video games are by nature co-operative or competitive are played between multiple live users. This may cause security issues in controlled environment facilities. Thus, systems and measures must be designed that allow for the beneficial and entertaining aspects of video gaming to be exploited within a controlled environment while addressing the myriad security concerns of that environment.
The present disclosure will be described with reference to the accompanying drawings. In the drawings, like reference numbers indicate identical or functionally similar modules.

Video game center for a controlled environment facility


A method and system are disclosed for dispersing gas bubbles in a multiphase mixture in a production tubing in an crude oil production well or in a riser connected to such a well, by means of one or more bubble breaker assemblies in which a plurality of orifices are arranged that are located in a substantially eccentric position relative to a central axis of the tubing. The use of eccentric orifices promotes the breaking up of large gas bubbles into a large amount of smaller gas bubbles, which are finely dispersed in the fluid stream and only re-coalesce slowly into larger bubbles.

Such a method and system are known from International patent application WO00/05485.
In the known method and system one or more bubble breaker assemblies are arranged in the conduit to create alternating flow zones of small and large cross-sectional areas with abrupt transition from the small cross-sectional areas to the large cross-sectional areas to produce a turbulent flow in which swirls and eddies are generated. The known bubble breaker assemblies consist either of venturi-like orifices that are concentric to the central axis of the conduit or of annular flow passages which are formed between the inner wall of the conduit and a central mandrel which is arranged in a concentric position.
U.S. Pat. No. 4,544,207 discloses a method for the uniform distribution of a two phase mixture by one or more orifice containing turbulence promoters which may comprise plates containing orifices of various shapes.
It is an object of the present invention to provide a method and bubble breaker assembly, which further enhance the mixing of gaseous and liquid fractions in the conduit such that the size of the gas bubbles is further decreased and the gas bubbles are distributed as a finely dispersed froth in the multiphase fluid stream.


A mixed conductor of this invention includes an electron conductor made of a carbon-based inorganic material imparted electron conduction by causing a main chain to have a π bond, and a proton conductor made of an inorganic material having proton conduction, and the electron conductor and the proton conductor are fixed to each other by one of or all of a covalent bond, intercalation, and inclusion.

The reaction layer of a fuel cell is formed between a proton exchange membrane and a backing layer and supports a catalyst for accelerating an electrochemical reaction. A combination of the reaction layer and the catalyst layer constitutes the electrodes of the fuel cell. In the reaction layer on an air cathode side, for example, protons passing through the proton exchange membrane and electrons transferred to the air cathode are conducted up to the catalyst, thus binding oxygen and protons diffused onto the catalyst. Namely, the reaction layer needs to exhibit both proton conduction and electronic conduction in order to improve the transfer loss of oxygen, protons and electrons. To this end, a mixture of poly electrolyte having catalysts supported on surfaces such as carbon particles (exhibiting electronic conduction) and Nafion (trade name, manufactured by E.I du Pont de Nemours, this applies hereafter) which exhibits ionic conduction is used in the fuel cell.
However, if a material having ionic conduction and a material having electronic conduction are used together, it is difficult to mix them up completely uniformly. As a result, protons and electrons cannot be uniformly transferred to all catalyst particles.
To solve this disadvantage, there has been proposed a mixed conductor which exhibits both ionic conduction and electronic conduction using one material.
For example, organic mixed conductors are disclosed in JP2001-202971A, JP2001-110428A, JP2003-68321A and JP2002-536787A.
In addition, inorganic mixed conductors conducting electrons and oxygen ions are disclosed in JP1998-255832A, JP1999-335165A, JP2000-251533A, and JP2000-18811A.