A rearview mirror assembly having a mirror, an imaging device and a monitor is provided for a vehicle. The monitor and the mirror may be integrated in the housing to provide the driver of the vehicle with at least two fields of view simultaneously.

The invention concerns a rearview mirror for vehicles, in particular, for commercial vehicles in which the mirror possesses an optical imaging apparatus.
U.S. Pat. No. 4,882,565 discloses a rearview mirror for vehicles in which an indicator device is integrated in the reflecting surface. The indicator device is provided with light from an illumination element located behind the mirror surface. With this device, simple warning signals or stylized presentations of various functional units can be presented and brought to the rearview mirror for attention. The images produced by a camera are not presented here.
Upon making a turn with a vehicle from a subordinate street into a main thoroughfare, normally the driver makes use of the rearview mirror before he turns. In the case of a right turn, he has not only the right side mirror with the visible rearward area but also the view to the right-front over the mirror in his field of sight. To be aware of risks or traffic on the left side, he must turn his head and if necessary, use the left rearview mirror. In heavy traffic, therefore, he is obliged to change both his direction of vision and the position of his head. Thus, while he is looking to one side, the other side is not being tended to. This can lead to dangerous situations.
The present invention develops a rearview mirror with an optical imaging device of such a nature that the disparate areas surrounding the vehicle will come to the attention of the driver.
The achievement of this objective is accomplished by the features of this invention.
By means of the provision of a monitor, which is placed in the rearview mirror, an image produced by an imaging device such as a camera can be transmitted to the monitor. The camera can be directed to a field of view, which is not in the view angle of the driver when he looks into the mirror. With the advantage of the invention, the driver in one glance can not only discern the area directly in the reflected angle of the mirror as well as the area in front of the mirror, but he can also see another area on the monitor in the mirror without needing to change his direction of view nor to turn his head. In the case of the monitor, advantageously a Liquid Crystal Display (LCD) image is employed. Likewise, the camera would advantageously be a charge-coupled device (CCD) camera.
In accord with an advantageous embodiment of the invention, the monitor is placed in the edge area of the mirror, that is, the mirror pane, in order not to interfere with the fundamental purpose of the mirror. This makes it possible that the monitor need not be integrated into the mirror pane but rather can be placed in a position under, beside or above the mirror pane. The placement of the monitor would be effected by an appropriate recess in the mirror housing.
In accord with another advantageous embodiment of the invention, the camera is likewise installed within the mirror housing, whereby the incident light on the camera is made possible by a corresponding opening in the mirror housing.
In accord with yet another advantageous embodiment of the invention, the camera is designed to be pivoted, thus increasing its field of regard so that different areas, i.e., fields of view about the vehicle can be brought into view and depicted in the monitor. When backing up is a necessity, then the zone behind the vehicle can be seen in the monitor.
In accord with another advantageous embodiment of the invention, a plurality of cameras is provided. With this multi-camera arrangement, switching among the individual cameras again allows various areas around the vehicle to be presented in the monitor.
If this latter plan is followed, then the pivoting of the camera becomes redundant. The respective camera can be placed in an optimal position, e.g., laterally, to scan the current area to be overseen. The camera for the backing up operation is logically to be installed on the back side of the vehicle.
If additionally a plurality of monitors are available, then under certain circumstances, selective switching from camera to camera becomes unnecessary, since one camera each can be apportioned to one monitor. Additionally, the possibility exists that on various monitors and particularly in different areas of presentation, one monitor can show additional data such as temperature, speed, assured clear distance behind, to the front, or to the side. The different presentation areas of a monitor should be understood in the sense that on the monitor, different items can be selected by the driver and shown by means of an image within an image format.
In accord with a further advantageous embodiment, the rearview mirror can encompass a first and a second monitor. The first monitor is connected with a camera in one rearview mirror, and the second monitor is connected to a camera in the other side rearview mirror of a vehicle. Thus, this arrangement allows a greater area around the vehicle to be scanned at one glance.
By means of an image and data memory apparatus, what is essentially a xe2x80x9cblack-boxxe2x80x9d function is achieved. For this purpose, the continuous images of the last five minutes from one or more cameras can be retained in memory. Additionally, relevant data such as temperature, weather, time, and speed can also be saved. By these means, an accident can be more easily reconstructed.
In accord with another embodiment of the invention, the image recorded by a camera from the mirror housing is angled differently than that of the mirror surface. This is to prevent showing the same image in the monitor as is normally reflected in the mirror.
By means of a digital zoom, that is, by the digital selection and adjustable magnification provided by the zoom, a function and an image component similar to that obtained by the pivoting of a camera are possible.
In accord with another advantageous embodiment, the monitor is integrated into the mirror such that the surface of the monitor is unnoticeable, or scarcely visible when in a non-activated state. This allows the monitor surface to be provided with a partial-reflecting means. Alternately, if the monitor is placed behind the mirror pane, then the area of the mirror pane, behind which the monitor is found, can be likewise be only partially or xe2x80x9chalf-silveredxe2x80x9d with reflecting means. For example, the reflective coating of the mirror pane in an area in front of the monitor is provided with distanced openings in order to obtain a locally higher transparency of the mirror pane. This interruption of the reflecting layer can be, for instance, in the form of thin stripes, relatively parallel to one another. Alternatively, the reflecting coating may be applied in the form of small, individual dots; i.e., stippled. If the reflective area is thus partially opened in such a manner, then the rearview potential of the rearview mirror is only limited by a small degree. Nevertheless, a high degree of local transparency of the mirror pane is gained, so that the monitor, in its activated condition, is visible, although in the non-activated condition, is practically invisible. This reduction of the areal density (i.e., reduced distribution pattern) of the reflective layer can, for instance, be executed by a laser, an etching or inscribing process, or by appropriate masking when the coating is applied to the mirror pane.


A safety light for use in vehicles is disclosed. The safety light would comprise a brake light and a seat belt signal light. The brake light would function as a normal window-mounted brake light would function, with the seat belt signal light functioning when a driver does not have their seat belt properly installed.

The present invention concerns that of a new safety light for use in vehicles.
U.S. Pat. No. 6,059,066, issued to Larry, discloses a means for indicating seat belt usage to observers outside a vehicle.
U.S. Pat. No. 5,877,707, issued to Kowalick, discloses a GPS based seat belt monitoring system.
U.S. Pat. No. 4,849,733, issued to Conigliaro, discloses a means for providing a visible display on the exterior of a vehicle to indicate whether the occupants have fastened their seat belts.
The present invention concerns that of a new safety light for use in vehicles. The safety light would comprise a brake light and a seat belt signal light. The brake light would function as a normal window-mounted brake light would function, with the seat belt signal light functioning when a driver does not have their seat belt properly installed.
There has thus been outlined, rather broadly, the more important features of a vehicle safety light that the detailed description thereof that follows may be better understood and in order that the present contribution to the art may be better appreciated. There are, of course, additional features of the vehicle safety light that will be described hereinafter and which will form the subject matter of the claims appended hereto.
In this respect, before explaining at least one embodiment of the vehicle safety light in detail, it is to be understood that the vehicle safety light is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The vehicle safety light is capable of other embodiments and being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of descriptions and should not be regarded as limiting.
As such, those skilled in the art will appreciate that the conception, upon which this disclosure is based, may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present vehicle safety light. It is important, therefore, that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention.
It is therefore an object of the present invention to provide a vehicle safety light which has all of the advantages of the prior art and none of the disadvantages.
It is another object of the present invention to provide a vehicle safety light which may be easily and efficiently manufactured and marketed.
It is another object of the present invention to provide a vehicle safety light which is of durable and reliable construction.
It is yet another object of the present invention to provide a vehicle safety light which is economically affordable and available for relevant market segment of the purchasing public.
Other objects, features and advantages of the present invention will become more readily apparent from the following detailed description of the preferred embodiment when considered with the attached drawings and appended claims.


Nonionic, hydrophobic photobleach compounds, especially those based on Si(IV) phthalocyanines, which are liquid at ambient temperatures and their use in a variety of consumer product compositions.

The present invention is in the field of photobleaches, especially photobleaches which are hydrophobically substituted metal or metalloid phthalocyanine compounds useful for treating fabrics, e.g., in consumer products such as laundry detergents.
Historically, photobleaches in consumer products have been ionic, usually as a result of sulfonation. Salt forms are typically used. This improves water-solubility and decreases interaction with common anionic surfactants used in detergents, but increases melting-point of the photobleach relative to a non-charged or non-salt material. Making a photobleach hydrophilic and giving it anionic charge also reduces its ability to partition into, and, upon exposure to light, to bleach oily soils and stains.
Recently, certain non-charged (nonionic) photobleaches have been developed. These include non-charged photobleaches among those disclosed in WO 98/32832 A, WO 98/32829 A, WO 98/32828 A, WO 98/32827 A, WO 98/32826 A, WO 98/32825 A, and WO 98/32824 A all published Jul. 30, 1998; and WO 97/05203 A and WO 97/05202 published Feb. 13, 1997. These materials can be quite hydrophobic and are useful in laundry detergents. They have an improved ability to treat oily soils.
While nonionic photobleaches generally have lower melting-points than ionic photobleaches, it is believed that the nonionic photobleaches thusfar disclosed, at least in pure form, are solids at ambient temperature. Recent advances in such photobleaches indeed appear to have focused on improving the photophysics without sufficient regard to certain design characteristics, including melting-point, which may be very important to the formulator of consumer products.
Chromophores such as phthalocyanines are typically of relatively high symmetry, thus nonionic photobleaches comprising such chromophores tend to have higher melting-points than many common nonionic organic compounds.
Thus, despite the recent advances, there remains a need for further improvements in photobleaches for use in consumer products. Specifically, there is an ongoing need for photobleaches which are more hydrophobic, more useful for treating synthetic or lipid-soiled fabrics, and are capable of being uniformly dispersed without milling the crystals. Uniform dispersion is very important to avoid a patchy effect in photobleaching of fabrics. Yet, in particular, there is no known consumer product composition having a hydrophobic, liquid photobleaching compound. Such a photobleach compound would offer new possibilities to the formulator of consumer products, could be deposited more uniformly, and would offer economic advantages such as low energy input and the ability to avoid solvents when compounding or formulating the photobleach.
It is accordingly an object of the present invention to provide further improvements in photobleach compounds, especially with respect to types wherein the photobleach is hydrophobic. Indeed it is an object herein to provide novel photobleaches which are hydrophobic nonionic liquids at ambient temperature; and to provide all manner of novel consumer product compositions comprising such compounds.
These and other objects are accomplished herein, as will be seen from the following disclosure.
See for example U.S. Pat. No. 5,872,248; U.S. Pat. No. 5,484,778; U.S. Pat. No. 5,763,602; Derwent 93-032275; EP-284,370 A; EP-296,876; EP-366,440; EP-484,027 A; EP 538,228 A; EP-596,184; GB 2,260,996; GB 2,279,657; GB 2,313,122; JP 3285998 (See Derwent 92-038692); JP 51/39044; JP 52/55339; JP 60/48047; JP 61/57536; JP 7292398 A (see Derwent 96-017535); KR 97-61275; KR 9102515 (see Derwent 92-321309); U.S. Pat. No. 3,860,484; U.S. Pat. No. 4,166,718; U.S. Pat. No. 4,209,417; U.S. Pat. No. 4,304,719; U.S. Pat. No. 4,368,053; U.S. Pat. No. 4,800,188; U.S. Pat. No. 4,806,514; U.S. Pat. No. 4,911,919; U.S. Pat. No. 5,135,717; U.S. Pat. No. 5,280,183; U.S. Pat. No. 5,346,670; U.S. Pat. No. 5,437,929; U.S. Pat. No. 5,482,514; U.S. Pat. No. 5,484,778; U.S. Pat. No. 5,561,106; U.S. Pat. No. 5,585,483; U.S. Pat. No. 5,665,689; U.S. Pat. No. 5,665,875; U.S. Pat. No. 5,679,661; U.S. Pat. No. 5,733,560; U.S. Pat. No. 5,824,800; WO 91/18006; WO 91/18007; WO 92/01753; WO 92/01753; WO 94/22960; WO 95/06688; WO 95/24267; WO 95/31526; WO96/29367; WO 97/05202; WO 97/05202; WO 97/05203; WO 97/10811; WO 98/14521; WO 98/25455; WO 98/32827; WO 98/32832; and WO 98/44052.
See also U.S. Pat. No. 3,094,536, Jun. 18, 1963; U.S. Pat. No. 3,927,967, Dec. 23, 1975; U.S. Pat. No. 4,033,718, Jul. 5, 1977; U.S. Pat. No. 4,240,920, Dec. 23, 1980; U.S. Pat. No. 4,255,273, Mar. 10, 1981; U.S. Pat. No. 4,256,597, Mar. 17, 1981; U.S. Pat. No. 4,318,883, Mar. 9, 1982; U.S. Pat. No. 4,497,741, Feb. 5, 1985; U.S. Pat. No. 4,648,992, Mar. 10, 1987; and U.K. Pat. Appl. 1,372,035 published Oct. 30, 1974; U.K. Pat. Appl. 1,408,144 published Oct. 1, 1975; U.K. Pat. Appl. 2,159,516 published Dec. 4, 1985; E.P. 285,965 A2; E.P. 381,211 A2 published Aug. 8, 1990; E.P. 484,027 A1 published May 6, 1992; and Japanese Kokai 06-73397 Derwent Abst. No. (94-128933) published Mar. 15, 1994.
In addition to the above, other references describe the synthesis, preparation and properties of phthalocyanines and naphthalocyanines; see Phthalocyanines: Properties and Applications, Leznoff, C. C. and Lever A. B. P. (Eds), VCH, 1989; Infrared Absorbing Dyes, Matsuoka, M. (Ed), Plenum, 1990; Inorg. Chem., Lowery, M. J. et al., 4, pg. 128, (1965); Inorg. Chem. Joyner R. D. et al., 1, pg. 236, (1962); Inorg. Chem., Kroenke, W. E. et al., 3, 696, 1964; Inorg. Chem. Esposito, J. N. et al., 5, pg.1979, (1966); J. Am. Chem. Soc. Wheeler, B. L. et al., 106, pg. 7404, (1984); Inorg. Chem. Ford, W. E, et al., 31, pg. 3371, (1992); Material Science, Witkiewicz, Z. et al., 11, pg. 39, (1978); J. Chem. Soc. Perkin Trans. I, Cook, M. J., et al., pg. 2453, (1988); J. Chin. Chem. Soc., 40, pg. 141, (1993); J. Inorg. Nucl. Chem., 28, pg. 899, (1966); Polymer Preps, 25, pg. 234, (1986); Chem. Lett., 2137, (1990); J. Med. Chem., 37, pg. 415, (1994).
The present invention encompasses improvements in a nonionic photobleach compound for consumer product application having (A) a metal or metalloid, preferably selected from Ga, Ge, Sn, Si and Al; (B) a chromophore, preferably selected from phthalocyanine and naphthalocyanine (wherein this encompasses both substituted and unsubstituted phthalocyanines and naphthalocyanines); and (C) one or two bonded ligands, preferably occupying axial positions. The improvement comprises at least one, covalently attached, hydrophobic, strongly crvstallinity-disrupting or symmetry-lowering substituent in said chromophore, said bonded ligand in axial position, or in combinations thereof; whereby said nonionic photobleach compound has crystal packing substantially disrupted to the extent that it is a liquid at ambient temperature.
xe2x80x9cAmbient temperaturexe2x80x9d is typically about 20xc2x0 C., but can vary from country to country and from season to season. As defined herein, however, xe2x80x9cliquid at ambient temperaturexe2x80x9d means specifically that the present photobleach compounds are liquid at a temperature below about 35xc2x0 C., including that they are liquid at at least one temperature in the range from 0xc2x0 C. to about 35xc2x0 C., more preferably, that they are liquid at all temperatures in the range from about 15xc2x0 C. to about 25xc2x0 C. Moreover with respect to melting-points of photobleaches herein, such melting-points are generally determined on samples of substantially pure photobleach materials, for example those which are substantially free from consumer product adjuncts or starting-materials of the synthesis. xe2x80x9cSubstantially freexe2x80x9d means that such adjuncts or starting-materials are removed to the extent practically possible. Likewise the term xe2x80x9csubstantially purexe2x80x9d as applied to the photobleaches herein means that the photobleach compound, for purposes of characterization, is accompanied by no adjuncts, starting-materials or impurities to the extent that such adjuncts, impurities, or starting-materials may be practically removed by normal purification techniques, such as chromatography, low-temperature crystallization, or the like.
In alternative terms, the invention encompasses a nonionic photobleach compound for consumer product application, preferably characterized by (A) a metal or metalloid selected from Ga, Ge, Sn, Si and Al; (B) a chromophore selected from phthalocyanine and naphthalocyanine; and (C) one or two bonded ligands, occupying axial positions; wherein said nonionic photobleach compound comprises at least one, covalently attached, substituent in said chromophore, said bonded ligand in axial position, or combinations thereof; wherein said covalently attached substituent is selected from the group consisting of hydrophobic, strongly crystallinity-disrupting or symmetry-lowering substituents; and wherein said nonionic photobleach compound is a liquid at ambient temperature.
The present nonionic photobleach compounds are useful in consumer products, as will be seen from the following disclosure.
The invention has many other ramifications and embodiments, and numerous advantages, as will also be seen from the disclosure. All percentages and proportions herein are by weight unless otherwise indicated. The units of parts per million or xe2x80x9cppmxe2x80x9d wherein 1 ppm=1 milligram per liter=0.0001% by weight may alternatively be used herein from time to time, especially for content of photobleach compound in a composition of the invention.
All documents cited herein are incorporated by reference in their entirety.
As noted in summary, the present photobleach compounds comprise covalently attached substituents which make the compounds very hydrophobic, substantially lower the symmetry, and reduce the melting-point.
In one preferred embodiment, said covalently attached substituent is attached to said ligands occupying axial positions.
In another preferred embodiment, said covalently attached substituent is attached to said chromophore.
It is especially suitable for various purposes, including convenience of synthesis and lower overall cost, to have the covalently attached substituent attached to the ligands occupying axial positions.
In a preferred embodiment, said covalently attached substituent comprises at least one hydrocarbyl moiety comprising about 10 or more carbon atoms; preferably said covalently attached substituent comprises at least one branch-point.
A xe2x80x9cbranch-pointxe2x80x9d of a covalently attached substituent herein is any stereochemical departure from a n-hydrocarbon structure which will result in an increased inefficiency of crystal packing or of liquid crystal packing of a pure hydrocarbon corresponding to the substructure having the branch-point.
Branch-points are non-limitingly illustrated by iso- and tert- hydrocarbon structures. For example, the following substructures contain branch-points:
In general, branch-points are not limited to carbon and hydrogen. For example, an amino nitrogen atom can act as a branch-point.
More preferably still, said axial ligand comprises at least two of said substituents and additionally comprises at least one covalently attached substituent comprising at least one hydrocarbyl moiety having about 12 or more carbon atoms. This creates a nonionic photobleach compound whose properties, especially with respect to crystal packing, are very heavily influenced by the ligand, counterbalancing the high symmetry and inclination to pack in a crystal lattice which is characteristic of the chromophore.
More generally, the present photobleaches include those having at least one of said substituents, wherein the substituents can be located on the chromophore or on the axial ligands, e.g., any of Sxe2x80x2-Sxe2x80x2xe2x80x3xe2x80x2xe2x80x3 in the nonlimiting illustrative structure below wherein the chromophore is based on a phthalocyanine.
Moreover, there can, in general, be two or more substituents meeting the present requirements on any of the rings of the chromophore, or anywhere in the molecule.
In highly preferred hydrophobic photobleach compounds herein, the metal or metalloid is Si(IV). While it is possible to substitute the chromophore rather than the axial ligands, in preferred embodiments, the photobleach compound has as the chromophore a phthalocyanine, preferably one wherein the phthalocyanine is free from any of said substituents. All the substituents meeting the present needs are thus located on the axial ligands.
A preferred nonionic photobleach compound herein has the formula: Si(IV)(Pc)L2 wherein Pc=phthalocyanine and L represents said axial ligands; and wherein each L can vary independently and is selected from the group consisting of: xe2x80x94OSi(R1)(OR2)2 wherein R1 is a hydrocarbyl moiety having 12 or more carbon atoms and R2 is a branched hydrocarbyl moiety having 10 or more carbon atoms. One such nonionic photobleach compound has the formula:
The present invention also includes all forms of consumer product composition comprising the photobleach compounds of the invent ion. Such consumer product compositions generally comprise the photobleach compound and at least one adjunct material which can vary widely, including, for example, propellants (for an aerosol delivery), organic solvents including fluorocarbons, adjuncts of detergents or of dry-cleaning products, or adjuncts of fabric conditioners. All that is generally required is that the novel photobleach compound be present. Typically, a consumer product composition herein comprises at least about 0.001 ppm of the nonionic photobleach compound of the invention.
While the invention can be used to treat fabrics or other surfaces encountered by the consumer of any kind, the present photobleach compounds are especially suitable for treating hydrophobic textile fabrics, including those having some yellowing, even when clean. The treatment can use any suitable method, whether aqueous or non-aqueous. For example, fabrics can be treated in a dry-cleaning operation using any known dry-cleaning medium, with the present compounds. One preferred treatment is for so-called xe2x80x9cdingyxe2x80x9d fabrics, which are often yellowed by the presence of complex lipid soils.
Thus, the invention encompasses a method of cleaning a dingy fabric comprising a step of treating the dingy fabric with a consumer product composition comprising a hydrophobic nonionic photobleach compound wherein said compound in substantially pure form is a liquid at ambient temperature; preferably the photobleach is a preferred compound of the invention such as a Si(IV) phthalocyanine bearing axial substituents of the type non-limitingly illustrated herein. Such a method extends to a variety of consumer product compositions, such as those in which the consumer product is a member selected from the group consisting of: (i) laundry or dry-cleaning pre-treaters; (ii) laundry detergents; (iii) fabric softeners; and (iv) aerosol or spray-based fabric treatments other than (i)-(iii).
The present invention also includes a process for providing intermediate compositions of formulated photobleaches for use in consumer products, or for improving ease of formation thereof, said process comprising the steps of: (a) providing a nonionic photobleach compound which in substantially pure form is liquid at ambient temperature; and (b) mixing said photobleach compound with one or more adjuncts, thereby forming an intimate mixture of said photobleach in said adjunct or adjuncts; whereby, by virtue of the liquid form of said nonionic photobleach compound, there is no need for high-energy mixing, milling, or use of solvents to accomplish good mixture.
Photobleach Compounds
As formulated in consumer products, in addition to the adjuncts required for making or delivering the full benefit of such compositions, the present invention requires that the inventive compositions comprise an effective amount of a particularly defined and selected photobleach compound.
The preferred photobleach compounds have no charged moieties, i.e., they are xe2x80x9cnonionicxe2x80x9d, and they are metal or metalloid phthalocyanines comprising one or two chemically bound ligands occupying axial positions.
The present compositions thus comprise a hydrophobic photobleach compound as an essential component. The term xe2x80x9chydrophobicxe2x80x9d is used in conjunction with the photobleaches to distinguish the photobleaches herein from xe2x80x9chydrophilicxe2x80x9d photobleaches which are well-known in the art: these hydrophilic photobleaches generally comprise at least one anionically charged group, such as a sulfonate group, which confers water-solubility.
The present photobleaches are generally hydrophobic to the extent that when placed in a two-phase mixture of water and common organic solvents such as methylene dichloride, they will preferentially and strongly partition into the organic phase, not the water phase. Hydrophobic photobleach compounds herein are non-charged, or xe2x80x9cnonionicxe2x80x9d.
All highly preferred photobleach compounds of the invention are sufficiently hydrophobic to partition at least partially from a phase which is more hydrophilic than triolein, into triolein.
Chromophore
Photobleaches herein generally comprise a chromophore in the form of a planar or distorted-planar extended cyclic system acting as a polydentate ligand occupying equatorial positions with respect to a metal or metalloid. Together, the chromophore, the metal or metalloid and one or two additional ligands occupying axial positions form a photoactive compound. Preferred chromophores are selected from unsubstituted phthalocyanine and naphthalocyanine (preferably phthalocyanine). Optionally, substituents may be attached to the cyanine provided said photobleach is not thereby rendered substantially soluble in water. Substituents, if present, are noncharged; sulfonate substituents are excluded from all preferred embodiments.
Metal or Metalloid
Photobleaches herein generally comprise a metal or metalloid selected from the group consisting of Si, Al, Ga, Ge and Sn, more preferably Si and Al, more preferably still, Si. The metal or metalloid, shown as xe2x80x9cMxe2x80x9d in the following structures, is bound to both to the chromophore and to ligands occupying axial positions, marked X or Xxe2x80x2 in these structures.
In highly preferred detergent compositions of the invention, the photobleach compound is selected from the group consisting of:
and mixtures thereof wherein X and Y can vary independently and represent axially bonded ligands.
Photobleach Precursor
Photobleaches herein are commonly prepared from a precursor compound. A common precursor is the dihydroxy Si(IV) phthalocyanine of formula:
xe2x80x9cLigandxe2x80x9d, Axial Position, Axial Site Available, xe2x80x9cAxial Ligandxe2x80x9d, xe2x80x9cBonded Ligandxe2x80x9d
The term xe2x80x9cligandxe2x80x9d herein most generally refers to an organic compound other than phthalocyanine or naphthalocyanine (thus specifically excluding inorganic moieties such as water, xe2x80x94OH, xe2x80x94Cl etc. as in the precursor compound above). The ligand is an organic compound capable of binding axially to a Si, Al, Ga, Ge or Sn (preferably Si(IV)) phthalocyanine moiety. The invention does not exclude Si(IV) phthalocyanines comprising one organic axial ligand and one xe2x80x94OH ligand, but preferably, when the metalloid is Si, the photobleach will have two non-OH organic ligands.
The terms xe2x80x9cbonded ligandxe2x80x9d or xe2x80x9caxial ligandxe2x80x9d or xe2x80x9cligand in axial positionxe2x80x9d herein are used to distinguish ligand which is actually chemically bonded to the metal or metalloid, from any other ligand, e.g., which is simply present in physical admixture with the metal or metalloid compound.
The term xe2x80x9caxialxe2x80x9d as in xe2x80x9caxial positionxe2x80x9d, or xe2x80x9caxial ligandxe2x80x9d, is used herein to indicate a position of bonding with respect to a metal or metalloid. Specifically, in the case of phthalocyanine compounds for example, the phthalocyanine chromophore occupies xe2x80x9cequatorial positionsxe2x80x9d while all non-phthalocyanine ligands occupy xe2x80x9caxial positionsxe2x80x9d. In Si(IV) phthalocyanines there are two axial positions, whereas in Al phthalocyanines, there is only one. Thus, a xe2x80x9cbonded axial ligandxe2x80x9d is by definition a ligand which is not the chromophore, bonded to the metal or metalloid.
On bonding to the photobleach precursor, a ligand molecule may lose a small portion of its mass, for example due to elimination of water or a silanol on reaction with a hydroxyfunctional photobleach precursor. For example when the molecule eliminated is water, the bonded ligand has a molecular weight of 1 less than that of the free or nonbonded ligand.
Photobleach Hue
The photobleaches herein can have any visible hue consistent with the chromophore. Hue preference of laundered fabrics tends to vary from one country or region to another, and can include blue, green or pink hues.
The present invention encompasses consumer product compositions, including pre-treaters such as stain-sticks or aerosol sprays free from detergent surfactants, as well as laundry detergents for laundering soiled garments or fabrics in dry-cleaning appliances, automatic washing machines or by hand. A xe2x80x9cdetergent compositionxe2x80x9d is a composition having any suitable form, such as granules, powders, tablets, liquids, gels, pastes or the like, and comprising an effective amount of at least one detersive surfactant capable of removing soils from soiled clothing and an effective amount of least one non-surfactant detergent adjunct. Other forms of consumer product composition forming part of the invention do not require the detersive surfactant.
Effective Amounts of Components
An xe2x80x9ceffective amountxe2x80x9d of a consumer product ingredient is an amount capable of at least partially improving the appearance thereof by removal, chemical modification, or physical altering of soil.
An xe2x80x9ceffective amountxe2x80x9d of a photobleach compound is any amount of a photobleach compound capable of improving the appearance of a fabric through any photophysical mechanism, be it catalytic or stoichiometric. The improvement may happen in dry-cleaning, washing or laundering stages, or in subsequent stages, such as line drying in the sun.
Typical xe2x80x9ceffective amountsxe2x80x9d of photobleaches can be very low, e.g., parts per billion, more typically a few parts per million up to about 10,000 ppm in a consumer product composition.
xe2x80x9cEffective amountsxe2x80x9d with respect to detersive surfactants are amounts consistent with exceeding the critical micelle concentration of a single detersive surfactant under the conditions of use, or, when multiple detersive surfactants are used, the in-use concentration of the combination of detersive surfactants is sufficient for forming micelles.
Levels of Photobleach Compound in Consumer Product Compositions
In general, the photobleach compounds herein can be used at any level providing photobleaching. However, low levels are preferred to avoid staining or overhueing. Suitable levels include from about 0.015 ppm to about 0.5%, more preferably from about 0.010% to about 0.050%, more preferably still from about 0.001% to about 0.01% of hydrophobic photobleach compound in a consumer product composition.
Adjuncts
Any adjuncts other than the photobleach compound or detersive surfactant can be useful herein. A xe2x80x9cnon-surfactant detergent adjunctxe2x80x9d is any component suitable for incorporation in a consumer product, e.g., a laundry detergent, provided that this component is other than a detersive surfactant or a photobleach. Such a component can include, for example, solvents, propellants, polymeric carriers or vehicles, builders, chelants, bleach systems, soil release polymers, softeners, perfumes and the like.
Preferred non-surfactant detergent adjuncts include bleach systems, (especially those comprising hydrophobic bleach activators such as nonanoyloxybenzene sulfonate and/or transition metal bleach catalysts such as Mn or Fe complexes of rigid macrocyclic donors and/or organic bleach boosters), enzyme systems (including both bleaching and non-bleaching enzymes), builders (including sodium tripolyphosphate as well as nonphosphate detergency builders), silicone/silica compounded antifoams, end-capped terephthalate-based soil release polymers, optical brighteners, and pro-perfumes.
In addition to adjuncts provided for directly consumer-useful purposes, the present photobleach compounds can be formulated with other optional components, for example external coatings and/or cationic additives, processing aids or the like.
Detersive Surfactants
A xe2x80x9cdetersive surfactantxe2x80x9d is an amphiphilic compound, typically at least partially water-soluble, preferably completely water-soluble, having at least one hydrophobic moiety, called a xe2x80x9ctailxe2x80x9d, typically comprising a linear or branched hydrocarbyl moiety comprising at least six carbon atoms, and at least one hydrophilic moiety, called a xe2x80x9chead-groupxe2x80x9d. The head-group may be charged or non-charged. Conmmon detersive surfactants include anionic, cationic, nonionic and zwitterionic types, extensively recited in patents of detergent formulators and other publications.
When the compositions of the invention are detergent compositions, they comprise, in addition to the photobleach compound, a detersive surfactant, suitably at levels of from about 0.1% to about 99.9%, more preferably from about 0.5% to about 50%, typically from about 1% to about 30% by weight of the detergent composition. In general, the detersive surfactant can be selected from the common commercial detersive surfactants sold for laundry detergent use, including especially anionic detersive surfactants, particularly alkylbenzene sulfonates, alkyl sulfates, methyl ester sulfonates, or mixtures thereof; and nonionic detersive surfactants, particularly alkyl alkoxylates, sugar-derived nonionic surfactants such as APG""s or glucosamides, or mixtures thereof. Mixtures of anionic and nonionic detersive surfactants at ratios of from about 1:10 to about 10:1 by weight can be especially useful. Any suitable chainlength or carbon content of the hydrophobe of these surfactants can be used, for example from about C8 to about C20, more typically from about C8 to about C17. Any degree or type of branching in the hydrophobe is acceptable. The alkylbenzene sulfonates are often used at lower carbon content, for example an average of about C10 to C12. When the surfactant is anionic, most commonly it is used in the sodium salt form, though other forms, for example potassium, can be used for known reasons such as to promote solubility. Any specialty surfactants, for example foam boosters, can be added if desired.
Polymeric Delivery Vehicles
The present photobleach compounds can, if desired, be formulated with a polymer as a delivery vehicle, for example to protect the hydrophobic photobleach herein from detersive surfactants or other adjuncts, or to help improve total amount or uniformity of deposition. Preferred polymeric delivery vehicles include thermoplastic polymers which soften or melt under conditions of use, e.g., those which are liquid or molten at temperatures less than about 95xc2x0 C., and water-soluble polymers. Which polymer delivery system to use, and how hydrophobic it should be, are highly dependent on the precise type of consumer product. For example, in laundry detergents, polyalkylene glycols and/or mixed polyalkylene glycols, such as polyethylene glycols, having average molecular weights of from about 150 to about 20,000, preferably between about 600 and about 10,000, more preferably still from about 3,000 to about 6,000, e.g., about 4,000 are very useful. Another group of water-soluble polymers are water-soluble polymers which include N as an amide, including, especially, water-soluble polymers comprising as monomeric units vinylamides such as N-vinylpyrrolidone and N-vinylacetamide as well as vinyl heterocycles such as N-vinylimidazole, N-vinyloxazolidone, N-vinyltriazole, 4-vinylpyridine, and 4-vinylpyridine-N-oxide; or poly-(N-isopropyl acrylarnide). Most preferred water-soluble polymer compounds in this group in accordance with this invention are polyvinylimidazole (PVI), or a copolymer of polyvinylpyrrolidone and polyvinylimidazole (PVPVI), most preferably polyvinylpyrrolidone (PVP). Preferably, these highly preferred amidofunctional water-soluble polymers have an average molecular weight of from 20,000 to 60,000. Also suitable herein as polymeric delivery vehicles are mixtures of two or more of any of the foregoing water-soluble polymers. Levels of such polymers in compositions herein can vary widely, but include, when present, at least about 0.001% to about 99.99%, more preferably from about 0.01% to about 25%, more preferably and typically from about 0.05% to about 0.5% of polymer.
Optional Componentsxe2x80x94Coatings
The present compositions can moreover include variants which comprise an external coating or other encapsulation means for the photobleach compound.
For example, when formulating the photobleach in an aqueous liquid detergent composition, it may be desirable to further coat or protect particles comprising the photobleach with a coating or hardening material such as a microcrystalline wax. Such coating or protection can help ensure better integrity of the photobleach delivery system particles on storage in the liquid detergent composition. Of course, such coatings can be used also when the photobleach delivery system is intended to be incorporated in granules, powders, pastes or tablet forms of the detergent composition.
Levels of such coatings in compositions herein can vary widely, but include, when present, at least about 0.001% to about 99.99%, more preferably from about 0.01% to about 25%, more preferably and typically from about 0.05% to about 0.5% of coating or encapsulating material.
Optional Components to be Formulated With Photobleach Compound
The present photobleaches can be coformulated with any adjunct materials other than cleaning actives. This includes cationic polymers such as cationic starches, polyethyleneimine polymers or copolymers, quaternary ammonium salts of the type used in fabric conditioners or through-the-wash softeners, or the like. Such cationic additives may further improve deposition of the photobleach on fabrics in certain detergent compositions, especially those wherein the detersive surfactant component is to a large extent nonionic rather than anionic.
Levels of optional components in compositions herein can vary widely, but include, when present, at least about 0.001% to about 90%, more preferably from about 0.01% to about 25%, more preferably and typically from about 0.05% to about 0.5% of the optional component or adjunct.
Any other optional component consistent with the spirit and scope of the invention may be added to the photobleach, provided that it does not result in a consumer product composition which provides no photobleaching.
Non-Surfactant Detergent Adjunct
Detergent compositions herein suitably comprise at least one nonsurfactant detergent adjunct. Preferably said nonsurfactant detergent adjunct comprises one or more members selected from the group consisting of: bleaching enzymes; non-bleaching enzymes; transition metal bleach catalysts; organic bleach boosters; bleach activators; oxygen bleach sources; preformed peracids; soil release agents; builders; chelants; conventional water-soluble sulfonated photobleaches; and mixtures of any of these adjuncts. Suitable levels of nonsurfactant detergent adjuncts in the inventive compositions can vary widely. For example, in detergent compositions of the invention, the composition suitably comprises from about 0.0001% to about 99%, more preferably from about 1% to about 90%, typically from about 20% to about 85% by weight of the detergent composition of at least one non-surfactant detergent adjunct.
Form of Detergent Compositions
When the compositions of the invention are detergent compositions, the compositions can have any suitable form, for example granules, tablets, pouches, syndet bars, gels, pastes or the like. Other suitable forms include heavy-duty liquid laundry detergents, substantially nonaqueous laundry detergents in liquid or solid form, and aqueous forms of any of said detergents.
The present invention has numerous advantages. For example, it can be used to deliver hydrophobic photobleaches to soiled fabrics. It is useful in nonaqueous cleaning, e.g., dry-cleaning. The invention. permits dispersing the photobleach into other materials with very low energy requirements and without organic solvents, and completely avoids the problems of dispersing crystalline photobleaches in other materials. The invention provides improved photobleaching of dingy soils. The invention accommodates a range of hydrophobic photobleaches, providing flexibility to the formulator. In short, the invention is a significant technical advance.
While the present photobleach compounds are. especially directed to use in consumer product compositions, especially for photobleaching detergents, the present compounds are useful for other purposes, for example as dyes, hueing agents, photodisinfectants and the like. The present invention includes all such benefits of the compounds, and all consumer product compositions containing same.
Moreover it is believed that the present compositions may also be useful in any other context or product in which a hydrophobic nonionic photoactive compound is required. Such applications include photodynamic therapy and the electronics industry.


A paste composition having a high thermal conductivity and a relatively low viscosity is used to provide a thermal conductive connection between an electronic component and a cooling device to increase the heat transfer rate between the component and the device cooling the electronic component. The paste composition comprises a non-aqueous dielectric carrier, thermally conductive filler particles and a specially defined dispersant comprising the self-condensation reaction product of a hydroxy fatty acid, the reaction product having an acid number of about 30-100. A 12-hydroxy stearic acid self condensed reaction product is the preferred dispersant.

1. Field of the Invention
The present invention relates to high thermal conductivity pastes which are used as a heat transfer means for cooling electronic components such as VLSI chips and, in particular, to a specific dispersant used in the paste to provide a paste having enhanced thermal conductivity and paste properties.
2. Description of Related Art
Electronic devices and components generate heat and in many applications the heat needs to be effectively dissipated for the device to function. In integrated circuit chips mounted in an array on substrates, the need to achieve greater computer speeds and the miniaturization of electronic devices has resulted in components which generate more heat and which require denser packing of the active components of the electronic device. The use of such components and denser packing is only practicable, however, when the heat generated is effectively removed from the active components and a number of techniques have been developed to cool such electronic components.
Liquid coolants are commonly employed in such high density cooling applications and various systems have been disclosed in the art for providing a separate cooling member to cool the component. Fins, channels, baffles, and other heat exchanger type devices have been developed to remove heat from the electronic component. Exemplary apparatus for cooling integrated circuit chips are shown in U.S. Pat. Nos. 5,177,667 and 5,294,830, the disclosures of both patents being herein incorporated by reference.
In most of these cooling devices there is an air space between the electronic component to be cooled and the cooling device which air space has a relatively low heat transfer rate. To overcome this problem, thermal compounds commonly referred to as thermal greases or thermal pastes have been developed to enhance the transfer of heat from the electronic component to the cooling device by contacting and connecting both surfaces and providing a high heat transfer conducting means. The thermal paste must have high thermal conductivity and preferably be an electrical insulator. The paste must also have a low viscosity and be compliant so that the thermal paste can be easily applied to the surfaces of the electronic component to be cooled and can conform with the microscopically rough surface of the electronic component which are often bowed or tilted to minimize air gaps which are detrimental to the cooling process. Low viscosity is also important because the electronic components and the solid bonds that attach the components to a substrate are fragile and the force needed to apply the thermal paste must be minimal. It is a further requirement that the thermal paste be able to withstand power cycling and the mechanical stresses arising from the differences in coefficient of thermal expansion of the electronic component, paste and cooling system over the life of the component without the paste degrading significantly in thermal conductivity or mechanically, such as experiencing phase separation between the liquid and solid components of the paste.
A number of thermal pastes have been developed to be used in electronic systems and, in general, the thermal paste comprises thermally conductive filler particles in a liquid dielectric medium along with other components such as dispersants, antioxidants, and stabilizers.
U.S. Pat. Nos. 5,094,769 and 5,213,704 provide a phase-stable, thermally conductive paste having a relatively constant thermal conductivity and viscosity for transferring heat from electronic components. A critical component of the paste is the use of a coupling agent such as an organosilane which has a functionality which is reactive with the thermally conductive filler particles and a functionality which is of similar polarity to the liquid carrier. The disclosures of these patents are hereby incorporated by reference.
In U.S. Pat. No. 5,098,609 stable high solids, high thermal conductivity pastes are disclosed which contain a stabilizing dispersant to inhibit liquid-solids separation and which facilitate incorporation of more solid fillers into the paste. Examples of stabilizing dispersants are monomeric acids; monomeric, oligomeric and/or polymeric fatty acid esters and salts thereof; petroleum sulfonates; and polyimides. Exemplary of fatty acid esters are the reaction products of hydroxy stearic acid (HSA) and a 5-18 carbon acid or acid chloride. Preferred dispersants are fatty acid esters which are the reaction product of 12 hydroxy stearic acid (12 HSA) and a 5-10 carbon aliphatic acid chloride or 5-18 carbon alicyclic acid chloride or aromatic acid chloride. 12 HSA reacted with itself to yield a polymeric/oligomeric material is also disclosed to be useful. Polyesters as disclosed in U.S. Pat. No. 3,778,287 to Stansfield and Hypermers made by ICI are disclosed in the patent as being useful as the stabilizing dispersant. The disclosures of both patents are hereby incorporated by reference.
Increasing demands of industry however, are requiring pastes having improved thermal conductivity in order to be used with the new computers and other electronic components now being developed. In general, higher filler loadings are needed for higher thermal conductivity pastes and while pastes having thermal conductivities ranging from 2.2-4.9 W/mK(watts/meter-degree K) are available the pastes tend to be too thick and stiff at the high filler loadings required for thermal conductivities greater than 3 W/mK. Hard, non-compliant and difficult to dispense pastes can not be used for most applications. In addition, commercial pastes and dispersants have shown higher and variable levels of ionics, particularly CIxe2x88x92, which presents a corrosion concern.
Bearing in mind the problems and deficiencies of the prior art, it is therefore an object of the present invention to provide a thermally conductive paste which may have a wide range of filler loading levels necessary to provide a wide range of thermal conductivity properties with relatively low paste viscosity, compliance, low ionics, paste phase stability and high electrical resistivity.
It is another object of the present invention to provide a method for cooling an electronic component comprising the use of a specially formulated thermally conductive paste to provide a thermal transfer means between the electronic component and the cooling mechanism.
It is yet another object of the present invention to provide high thermal conductivity compliant pastes using 12-hydroxy stearic acid derived polymeric dispersants with Acid Nos. in the range of 30-100.
Still other objects and advantages of the invention will in part be obvious and will in part be apparent from the specification.
The aforementioned objects and advantages are achieved in the present invention which relates in one aspect to a paste having a high thermal conductivity comprising:
a non-aqueous dielectric liquid carrier;
a solid thermally conductive filler dispersed in the liquid carrier; and
a dispersant which is a polyester self-condensation reaction product of a hydroxy fatty acid or mixture of hydroxy fatty acids, the polyester reaction product having an Acid No. of about 30-100, preferably 45-85 and most preferably 50-75. The hydroxy fatty acid is preferably 12-hydroxy stearic acid (12 HSA) and the preferred polyester reaction product is a self-condensation reaction product of 12-HSA.
In another aspect of the invention, a method is provided for cooling an electronic component comprising:
providing an electronic component to be cooled;
providing a cooling means surface proximate to the electronic component; and
applying a layer of a thermally conductive paste comprising a polyester self-condensation reaction product of a hydroxy fatty acid, preferably 12-HSA, having an Acid No. of about 30-100, preferably 45-85 and most preferably 50-75, to the electronic component surface and to the cooling means surface to provide a thermal paste connection between the electronic component and the cooling surface.
The filler particles which may be used in the invention may be selected from a wide variety of materials which exhibit a relatively high thermal conductivity such as boron nitride, vanadium boride and aluminum spheres. The particles are preferably electrical insulators. The preferred shape is spherical or cubic so that packing density is maximized while providing a low viscosity of the dispersion of particles in the liquid dielectric carrier. Other shaped materials such as platelets may be used. A mixture of particle size distribution is preferred.
The thermally conductive filler particles are preferably treated before they are dispersed in the liquid carrier so that their surface is modified. The particles may be modified by heat treating such as calcining in air in order to remove low surface energy organic contaminants absorbed from the ambient so they have a higher surface energy than the liquid carrier and are wetted by the liquid carrier. Exemplary metal fillers which may be used in the invention include, aluminum, silicon, copper and silver. Ceramic fillers such as silicon carbide, aluminum nitride, boron nitride, vanadium boride, diamond, aluminum oxide, zinc oxide, magnesium oxide and silicon dioxide may be employed. Mixtures of fillers may also be utilized to provide a paste having certain features depending upon the application. It is preferred that the particle size of the solid fillers be between 0.05 xcexcm and 20 xcexcm although lower and higher particle sizes may also be used.
The thermally conductive filler particles in the paste composition will generally be, in volume %, in a minimum amount of about 25% and usually about 50 to 85%, preferably, 60 to 80%.
The liquid carrier is typically an oily, solvent cleanable dielectric fluid preferably a hydrocarbon liquid carrier, which is nonpolar and chemically saturated so that it does not absorb moisture and thereby cause corrosion of the electronic component. For the resulting paste composition to be mobile and compliant, the liquid carrier typically has a viscosity of approximately 1, e.g., 5 centipoise to about 500 centipoise at 100xc2x0 C. Dielectric fluids such as paraffinic hydrocarbons, polyphenylether oils, silicone oils, glycerides and preferably mineral oil and synthetic mineral oil (e.g., synthetic poly(alpha-olefin)) may be used. The most preferred liquid carrier because of its demonstrated effectiveness is chemically saturated poly(alpha-olefin) having a viscosity of approximately 2-150 centipoise preferably 40-120 centipoise at 100xc2x0 C. It is preferred that the polarity of the liquid carrier should preferably match the polarity of additives which may be used in the paste composition. A matching polarity promotes mutual affinity so that phase separation of the paste is minimized. It is most preferred that the polarity of the liquid carrier be nonpolar so that the affinity of the paste for moisture will be low and thus there is no corrosion concern.
The liquid carrier comprises about 5 to 55 volume % of the paste composition, preferably 5% to 40%.
It is an important feature of the invention that a specially defined dispersant material be used in the paste composition to provide a paste having the desired thermal conductivity and paste properties. Broadly stated, it has been found that when a hydroxy fatty acid or mixture of hydroxy fatty acids is self condensed and the reaction controlled to produce a reaction product having an Acid No. of about 30-100, use of this reaction product as a dispersant provides a thermal paste having enhanced thermal and paste properties. Acid No. values less than about 30 and above about 100, e.g., 200, may be used for certain applications requiring a thicker paste. The Acid No. is a well known value associated with the acid strength of a substance and is defined as the milligrams (mgs) of KOH required to neutralize the acid in a one gram sample of the product being measured. The higher the amount of acid in the sample the more KOH needed to neutralize the acid and the higher the Acid No.
Polyesters derived from hydroxy fatty acids are well known and a number of such polyesters and the method for making the polyesters is shown in U.S. Pat. No. 3,778,287 supra. Basically, the polyesters are obtained by heating the hydroxy fatty acid or a mixture of such acids or a mixture of a hydroxy fatty acid and a carboxylic acid optionally in the presence of an esterification catalyst, preferably at a temperature in the region of 160xc2x0 to 200xc2x0 C. until the required polyester has been obtained. To make the paste compositions of the present invention the course of the self-condensation esterification reaction would be followed by periodically measuring the Acid No. of the reaction mixture so that the reaction can be stopped when the Acid No. is within the desired range of about 30-100. Water is formed in the esterification reaction and is removed from the reaction medium by passing a stream of nitrogen over the reaction mixture or, preferably, by carrying out the reaction in the present of a solvent such as toluene or xylene and azeotropically removing the water as it is formed. The resulting polyesters can then be isolated in a conventional manner for use to make the paste composition.
Salts of the polyesters may also be employed in the invention and include alkali metal salts such as sodium and potassium and alkaline earth metal salts such as calcium, barium, magnesium and titanium. These salts may conveniently be obtained, for example, by heating the polyester with an oxide, hydroxide or carbonate of the metal at elevated temperatures. Amine salts may also be suitably employed.
The hydroxy fatty acids useful to form the reaction products preferably contain from 12 to 20 carbon atoms and it is highly preferred that there be between 8 and 14 carbon atoms between the carboxylic acid and hydroxy groups. As specific examples of such hydroxycarboxylic acids there may be mentioned ricinoleic acid, 5-, 7-, 9-, 10- and 16-hydroxy stearic acids and 12-hydroxy stearic acid. Mixtures of the hydroxy fatty acids may be used. Also, the commercially available hydrogenated castor oil fatty acid which contains in addition to 12-hydroxy stearic acid minor amounts of stearic acid and palmitic acid may be used.
A highly preferred embodiment because of its demonstrated effectiveness is the reaction product of 12-hydroxy stearic acid (12-HSA) with itself(self-condensation) to form a polyester having an acid number of about 30-100, most preferably 50-75. As shown herein below in the examples, these 12-HSA polyesters enable the making of a paste composition having a high thermal conductivity with a paste viscosity desired for use on electronic components.
The range of the dispersant in the paste composition is generally about 1 to about 10 weight %, preferably 2-7%, e.g., 3-5%.
Other materials may be utilized in the paste composition as known in the art to provide particular desired effects. Thus, the stability of the paste composition may be enhanced by the addition of chemically inert particles of high surface area to resist phase separation by absorbing excess liquid carrier in those situations where the electronic component power cycling leads to thermal/mechanical stressing of the paste composition and a propensity for the paste composition to bleed. Fumed silica or other such particles may be incorporated in the composition to increase the capacity of the paste composition to avoid irreversible bleeding. As discussed in U.S. Pat. No. 5,094,769 supra, the addition of a polymer such as polyisobutylene to a paste composition enhances the shear stability of the composition. It would also be advantageous to incorporate an antioxidant in the paste composition so that any exposure of the compound to oxygen or other oxidizing agents will not cause a chemical change causing phase separation.
In a highly preferred embodiment of the invention, aluminum/aluminum oxide fillers having a particle size of 0.1-15 xcexcm and poly(alpha-olefin) oil is preferred. The preferred dispersant is the self-condensation reaction product of 12-HSA having an acid number of about 50-75. The composition preferably comprises about 60-80 volume % filler, preferably 70-74%, about 2-7 weight % of the polyester dispersant and the balance poly(alpha-olefin)oil.
The paste composition are of low enough viscosity to be mobile during modular assembly to follow the surface contour of the electronic component but viscous enough so as to be stable mechanically when applied in small gaps to form the heat conductive path especially when exposed to power fluctuations. In state of the art semiconductor components, these gaps may be as low as 5 mils or less to minimize the length of the thermal path. This small gap causes high shear forces to be applied to the thermal compound which adds to the stability problem. To satisfy these criteria as well as accomplishing all of the other advantages provided by the thermally conductive compounds of the present invention, it is preferred that the paste composition comprise about 60% to 80% by volume filler particles, about 2% to 7% by weight dispersant and the balance being the liquid carrier. It is desired that the pastes have a thermal conductivity above about 2.8 W/mK, preferably above about 3.5, with a viscosity less than about 20,000 Pa-sec.
Preferred paste viscosity are below about 12,000 Pa-sec, preferably about 6,000-10,000 Pa-sec and above about 3,000 Pa-sec.
The paste compositions of the present invention may be made by any means known to those skilled in the art. Generally, the dispersant and liquid carrier are blended and then the solid filler is added gradually with continual stirring. This mixture of solids and liquids is then milled using known techniques (e.g., roll mill ) to produce a homogeneous paste. The paste may then be stored or used in the desired application. In a preferred embodiment, the filler particles are treated with a solution of the dispersant in a non-aqueous solvent such as hexane. The heterogeneous mixture is stirred for adsorption of the dispersant on the particles. The solvent is removed by heat and vacuum. The oil carrier is then blended with the treated particles and the slurry homogenized preferably with a roll mill.

Polyester dispersants for high thermal conductivity paste

International Business Machines Corporation


Dislcosed are methods and compositions for producing weight loss in a mammal by administration of a composition containing a weight loss effective amount of a noradrenaline stimulating compound such as ephedrine, mahuang (a plant source of ephedrine alkaloids), citrus aurantium (bitter orange), synephrine, norephedrine, psuedophedrine, a methylxanthine, such as caffeine or guarana, and a botanical COX inhibitor such as resveratrol polygonum cuspidatum, scutellaria baicalensis, turmeric, curcumin, rosmary, green tea, ocimum sanctum (holy basil), or ginger, instead of an NSAID such as aspirin, and optionally a free fatty acid reducing compound. The thermogenic formula is coupled with a growth hormone stimulating formulation containing L-arginine or L-omithine, L-lysine, and a free fatty acid reducing agent such as nicotinic acid. The thermogenic formula would preferably be administered in the daytime, and the growth hormone producing formula at nighttime. The two compositions form a system of AM and PM weight loss strategy for the therapeutic intervention of obesity.

This invention relates to methods and compositions for producing weight loss in mammals.
One of the greatest problems confronting modem society in economically successful countries today is obesity. Unfortunately, obesity brings with it the conditions that are ripe for the more serious disease of diabetes.
Among the many possible solutions for treating obesity are formulations of weight loss products that work with some of the basic biochemical processes involved in fat metabolism. This process has been exploited through pharmaceutical intervention at the neurocrine level as well as at the level of fat cells themselves, or the way fat cells metabolize fats in brown adipose tissue.
The term thermogenisis has been coined to describe the process whereby food intake is converted to body heat through the metabolic process of caloric conversion. In obese people, certain metabolic defects associated with the thermogenic process begin to appear. These metabolic predispositions manifest in a number of identifiable biochemical syndromes that can be attacked through therapeutic intervention with agents that over-ride the cascade of events leading to obesity.
One of the more natural approaches to starting artificial thermogenisis, that is, thermogenisis that is unrelated to food consumption, is the use of plant derived substances that contain ephredine or ephedrine like compounds such as ma-haung or ephedra. Ephedra is an herb that grows wild in parts of the western United States. Ephedra contains ephedrine, an alkaloid that stimulates the production of catecholamines such as norepinephrine. Norepinephrine or noradrenaline is presumed to start the thermogenic process by stimulating metabolism in fat cells via the neurocrine axis that involves beta-adrenergic receptors. This in turn results in lipolysis, or the liberation of fat in fat cells via an increase in the basal metabolic rate. This pharmacological intervention results in weight loss in lean, obese, and post-obese human subjects and has been demonstrated in clinical studies (Dulloo, A G and Miller D S, Wrld Rev Nutr Diet 50: 1-56 ;1987).
Ephedra (also known by its Chinese name, MaHuang) has also been combined with methylxanthines such as caffeine, and the prostaglandin inhibitor aspirin, in a three component weight loss formula (U.S. Pat. No. 5055460). Caffeine and aspirin have been shown to potentiate the thermogenic action of ephedrine (Dulloo A. G., Intl. Jour. Obes.; 1993, 17 (Suppl. 1), S35-S40). An increase in catecholamine release as a result of pharmacological intervention with thermogenic agents leads to a blunted response on metabolism because of negative feedback systems associated with biochemical phenomena that take place in the synaptic junction. These negative feedback control systems involve adenosine, free fatty acids, and prostaglandins. The methylxanthines such as caffeine work to overcome the negative feedback related to adenosine, and the aspirin inhibits cyclooxygenase, the enzyme responsible for synthesizing prostaglandins, and a new element has been added in the instant invention by the optional inclusion of nicotinic acid to lower free fatty acids. By inhibiting these negative feedback controls, the thermogenic or up-regulated metabolic effect produced by exogenous administration of agents capable of increasing nor-adrenaline can be potentiated.
One example of the magnitude of potentiation that can be achieved by combining a nor-adrenaline increasing agent such as ephedra, with a prostaglandin inhibitor such as aspirin to reduce feedback inhibition is the study conducted by Dulloo and Miller (Am J Clin Nutr 1987;45:564-9). In this study, aspirin and ephedra together more than doubled the weight loss in mice when compared to the effect of ephedra alone. Aspirin by itself resulted in no weight loss. Ephedra alone resulted in reduced body fat and weight and reduced obesity, but did not reverse obesity, whereas aspirin and ephedra together actually reversed obesity.
The use of aspirin to inhibit cyclooxygenase and thereby reduce prostaglandins is believed to be the mechanism of action that explains its anti-inflammnatory activity. Aspirin is one of the class of compounds known as non-steroidal anti-inflammatory drugs, otherwise known as NSAIDs. These drugs work by inhibiting cyclooxygenase 1, the enzyme that synthesis prostaglandins from arachidonic acid. Prostaglandin E-2 is a pro-inflammatory prostaglandin. But a single large dose of aspirin only inhibits cyclooxygenase partially, but not completely. Prostaglandin levels return to baseline levels within the next 6 hours. In U.S. Pat. No. 5055460, the preferred range for the dose of aspirin is from 200-1000 mg., with the particularly preferred unit dose being 300 mg. of aspirin. This amount of aspirin, with caffeine, and ephedra, is recommended to be taken 1-6 times per day. Yet even a single dose of 300 mg. per day of aspirin is capable of causing gastric erosion in healthy young adults in 5-7 days. Even more serious gastric bleeding would occur if up to six doses per day of this amount of aspirin were to be consumed. The use of aspirin to potentiate the thermogenic effects of ephedra or any other nor-adrenaline, catacholamine stimulating compound is therefore dangerous.
There is a definite need for a safer thermogenic triad that can inhibit the negative feedback produced by prostaglandins, without the side-effects of gastric erosion produced by the NSAID drugs like aspirin. There is also a need for a prostaglandin inhibitor formula that is more effective at suppressing cyclooxygenase and reducing prostaglandins with a single dose, and provide long term reduction of prostaglandins over an 8-24 hour period. There is also a need for a prolonged activity thermogenic formula that increases metabolism all day from a single dose, while at the same time prostaglandin""s are being suppressed in parallel over the same time period. There is also a need for a more complete suppression of the negative feedback produced by catecholamine stimulated free fatty acid release.
One attempt to over come the side-effects associated with the use of aspirin in the thermogenic triad has been to substitute white willow bark, which contains salicylic acid, for the aspirin component. Chemically, aspirin is acetylsalicylic acid, which is effective at inhibiting cyclooxygenase, and thereby lowers prostaglandin levels, whereas salicylic acid or white willow bark minimally effective at inhibiting cyclooxygenase, and therefore is not as effective as aspirin at potentiating the thermogenic effects of compounds such as ephedra.
A much safer and more effective composition for the thermogenic triad would be the use of a COX inhibitor other than aspirin. COX-2, or cyclooxygenase-2 inhibitors inhibit cyclooxygenase and reduce prostaglandins without producing the degree of gastric erosion associated with NSAID drugs such as aspirin. However, many COX-2 inhibitors have a short half-life, and do not keep prostagladins suppressed completely or in a prolonged fashion over a 6-24 hour period. In addition, the turnover rate for cyclooxygenase is fairly short.
Another attempt to formulate a weight loss product is described in U.S. Pat. No. 5798101. This patent is directed to herbal compositions to reduce weight and help suppress appetite consisting of St. John""s Wort and ephedra with or without caffeine. These formulations do not include a prostaglandin inhibitor such as aspirin or a COX-2 inhibitor, so the thermogenic component (the ephedra) would be less effective at driving metabolism because of the negative feedback from prostaglandins. The St John""s Wort is present to produce an effect on serotonin, a neurotransmitter involved in mood and carbohydrate craving. Thus, its function in the formulations described in this patent is as an appetite suppressant, not as a component in the thermogenic triad of ephedra, aspirin, and caffeine.
Growth hormone (GH) has been implicated in a number of metabolic effects. Administration of exogenous growth hormone by injection has been shown to accelerate body fat loss, and produce anabolic effects in obese human subjects (Kim et al, Horm Res 1999;51:78-84). Growth hormone secretion is regulated by two hypothalamic neurohormones; growth hormone releasing hormone (GHRH) and somatostatin (SRIH). GHRH stimulates growth hormone while SRIH has a inhibiting influence. Insulin like growth factor I (IGF-1), mediates the biological actions of growth hormone through negative feedback. A number of nutritional, dietary, and metabolic factors influence the growth hormone-insulin-like growth factor (GH-IGF I) interaction. Insulin levels are elevated in obesity, and high insulin levels also suppress growth hormone production.
Obese people have a blunted or suppressed GH release, even when subjected to growth hormone injections or other nutritional components that have an effect on growth hormone release in normal healthy subjects. Obese people have high levels of circulating free fatty acids (FFA), and free fatty acids have been shown to suppress growth hormone release (J Clin Endocrinol Metab 84: 1234-1238, 1999). Plasma free fatty acids and triglycerides can be reduced by oral administration of nicotinic acid, or esters, analogues, or pro-drugs of nicotinic acid such as 5-methylpyrazinecarboxylic acid 4-oxide (Acipimox, Pharmacia-Upjohn), beta-pyridylcarbinol, mesoinositol-hexanicotinate, xantinol nicotinate (Eur. J. Clin. Pharmacol. 16, 11-15, 1979, and Med Sci. Sports Exerc., Vol. 27, No. 7; 1057-1062, 1995).
Surprisingly significant differences exist in the magnitude and duration of plasma free fatty acid reduction from nicotinic acid and its esters, prodrugs, or analogues when the drug is given during the daytime versus the nighttime. If nicotinic acid (niacin) is given in the daytime, it reduces free fatty acids temporarily, but then there is a rebound effect. If given nocturnally, as a constant infusion at night from 8:00 PM to 6 AM, nicotinic acid and its complexes produces a 24 hour reduction in free fatty acids, without the rebound effect. This is particularly important for diabetics and people with type IV hyperlipoproteinemia, who experience a significant rise in triglycerides during the day as a result of a high carbohydrate diet. A slow-release formulation of nicotinic acid or like compound, if taken at night, will cause a dramatic reduction in 24 hour free fatty acid and/or triglyceride levels, and these will remain lowered for at least 24 hours until the next nocturnal dose is taken the following evening.
Growth hormone causes lypolysis, which results in an increase in circulating free fatty acids in plasma. This increase in free fatty acids produces a negative feedback inhibition of growth hormone production. But because free fatty acids are already elevated in obesity, obese individuals have this characteristic blunted basal growth hormone production, as well as when subjected to exogenous growth hormone injections. Elderly subjects also show suppressed spontaneous GH release, and reduced response to growth hormone stimulating agents.
L-arginine is an amino acid that has a pronounced effect on growth hormone and insulin-like growth factor-1. Oral administration of L-arginine can increase growth hormone production in normal non-obese subjects, but less so in obese subjects. In healthy postmenopausal women, 9 grams of L-arginine per day increased growth hormone by 72% (J. Lab Clin Med;135: 231-7; 2000). L-arginie stimulates growth hormone production in obese individuals, but is blunted by the negative feedback produced by high levels of circulating free fatty acids. Pharmacological reduction of free fatty acids in conjunction with injections of growth hormone releasing hormone (GHRH), helps to overcome the suppression of growth hormone in obese and elderly subjects (J Clin Endocrinol Metab, 81:3998-4001, 1996).
The amount of L-arginine needed to stimulate growth hormone secretion is fairly large, usually greater than 500 mg. To get a significant increase in growth hormone production, most studies have employed daily doses above 3 grams, and in many cases 9-30 grams. Since L-arginine is not an inexpensive substance, it would be of great advantage to be able to reduce the dose of L-arginine, and still stimulate significant increases in growth hormone. It has now been found that this is possible by incorporating lower doses of L-argie with the amino acid L-lysine, and a free fatty acid lowering substance such as nicotinic acid.
Free fatty acids follow a diurnal rhythm. During the daytime, when carbohydrates are being consumed, lipolysis is inhibited by insulin, and the free fatty acid level is low. At nighttime, while sleeping, carbohydrates are not being consumed, and consequently free fatty acids are elevated. High free fatty acids at night inhibit growth hormone production, particularly in obese people, and obese subjects have higher levels of circulating free fatty acids than non-obese subjects. Furthermore, catecholamines such as noradrenaline, stimulate free fatty acid release which inhibits lipolysis in adipose or fat cells. Compounds such as ephedra stimulate catecholamine production during thermogenisis, which in turn elevates free fatty acids. The free fatty acids thus serve as negative feedback for fat metabolism (lipolysis), much like the prostaglandins and adenosine previously described. Therefore, there is also a need to keep free fatty acids suppressed during the daytime, when the thermogenic components are ingested.
It is the object of the present invention to provide safer and more effective weight-loss compositions that combine the anti-obesity properties of two types of metabolic formulations that involve different biochemical aspects. The first compositions, designed to be taken during the day-time (AM component), and preferably in the morning, consist of new and improved thermogenic formulations. The second compositions, which should preferably be taken at night-time (PM component) consist of growth hormone stimulating substances. By stimulating thermogenesis during the day time to metabolize fat, and stimulating more effective growth hormone production at night, and mobilizing fat, a dual action, or two pronged attack, is directed at weight reduction. This takes advantage of a 24 hour biochemical strategy that marshals the best functionality from two of the most well documented weight loss systems currently studied.
The clinical efficacy of the thermogenic triad consisting of (1) a nor-adrenaline stimulating agent such as ephedra, (2) aspirin to inhibit prostaglandins, and (3) the methyl-xanthine, caffeine, has been well documented in numerous medical journals, but the safety of the aspirin component is a real issue. Furthermore, side-effects from the ephedra are directly related to a spiking of blood levels, or too rapid release. The same problem exists with the caffeine component. Jitteryness, nervousness, and heart palpitations are commonly experienced side-effects associated with high doses and rapid absorption of ephedra and caffeine. Botainical sources of caffeine include guarana (paullinia cupana), and mate (ilex paraguariensis), plants that grow in South America, and green tea, cola nuts, coffee, and cocao. Nicotinic acid has not been previously used as part of any thermogenic strategy. The efficacy of growth hormone treatment in pharmacological intervention of obesity has been hampered by the blunted response to injections of OHRH, and the lower basal production that occurs in obese people. Nevertheless, the association between growth hormone and obesity has been well documented.
It is a further advantage of the invention contained herein to describe side-effect reducing thermogenic formulations that could be consumed by obese individuals for prolonged periods of time without the fear of gastric erosion. Still another benefit is the prolonged activity of the sustained-release formulations that avoid any spiking of blood levels. Yet still another advantage is to provide a more effective growth hormone stimulating composition that more effectively increases growth hormone production in obese individuals as well as elderly and normal healthy subjects. Furthermore, the growth hormone stimulating compositions described herein over come the blunted response to growth hormone stimulation in obese people due to suppression by free fatty acids. This invention also provides for growth hormone formulations that are more effective with lower doses of the amino acid L-arginine, through the inclusion of L-lysine, and a free fatty acid reducing substance such as nicotinic acid. Lastly, the optional inclusion of nicotinic acid into the thermogenic compositions provides for more effective suppression of catecholamine induced negative feedback from free fatty acid release. By combining the metabolic enhancing formulations during the daytime with the growth hormone releasing formulations during the nighttime, a 24 hour formulation strategy is provided that is more effective than either formulation alone, or any individual component alone.
The present invention is directed to compositions of noradrenaline stimulating agents such as ephedra, citrus aurentium, or other botanical source of adrenaline stimulating alkaloids, a botanical COX inhibitor such as resveratrol contained in polygonum cuspidatum, and a methyl-xanthine such as caffeine, or a botanical source of caffeine, that inhibits adenosine, and therefore overcomes feedback inhibition of catecholamine release, and optionally, a free fatty acid reducing compound such as nicotinic acid or an analog, or ester of nicotinic acid, This thermogenic formula is coupled with a more effective growth hormone stimulating composition of L-arginine and L-lysine or L-ornithine and L-lysine and nicotinic acid, or analogs, or esters of nicotinic acid such as inositol-hexanicotinate, 5 methylpyrazinecarboxylic acid 4 oxide (Acipimox), xantinol nicotinate, pyridylcarbinol, or arginine nicotinate.
Salts, esters, peptides,derivatives, or complexes of L-arginine and L-lysine or L-ornithine and L-lysine may be used for the growth hormone stimulating agent, and any free fatty acid reducing agent may be used for the nicotinic acid component. Long acting preparations of nicotinic acid are preferred, particularly, sustained-release formulations, so that they can be administered at night, to keep 24 hour free fatty acids reduced. Ideally, these long acting preparations would release the niacin from about 6:00 PM to 6:00 AM, or about 12 hours.
The thermogenic formula would stimulate metabolism and produce lypolysis during the daytime when people are active, and the growth hormone stimulating compositions would be taken at night, when carbohydrate consumption and insulin are at a minimum, and free fatty acids are at their peak.
In its broadest sense, the present invention is directed to a method for producing weight loss in a mammal by administering a composition containing a weight loss effective amount of a noradrenaline stimulating compound such as ephedrine, mahuang (a plant source of ephedrine alkaloids), citrus aurantium (bitter orange), synephrine, norephedrine, psuedophedrine, a methylxanthine, such as caffeine or guarana, and a COX-2 inhibitor such as resveratrol, polygonum cuspidatum, scutellaria baicalensis, white willow bark, turmeric, curcumin, rosmary, green tea, ocimum sanctum (holy basil), or ginger, instead of an NSAID such as aspirin. The preferred COX-2 inhibitor would be resveratrol from a botanical source such as polygonum cuspidatum or polygonum multiflorum.
Polygonum cuspidatum, a member of the buckwheat family (polygonaceae), commonly known as japanese knotweed. This plant is a native of eastern Asia, but also grows wild throughout northeastern America and southern Canada. The roots Polygonum cuspidatum contain a large amount of resveratrol, a stilbene which is a powerful anti-oxidant, and exhibits anti-inflammatory, anti-mutagen, and anti-carcinogenic properties. Resveratrol also inhibits blood platelet aggregation, making it a beneficial cardiovascular compound. Recently, resveratrol was found to inhibit COX-2 by dose dependently reducing prostaglandin,E-2 (PGE2) production in human mammary epithelial cells. The dried roots of Polygonum cuspidatum contain about 5-8% resveratrol. By using various extracting techniques to concentrate the amount of resveratrol in Polygonum cuspidatum, high yield powders have been obtained that contain up to 20% resveratrol. Therefore, 100 mg. of Polygonum cuspidatum extract will deliver 20 mg. of actual resveratrol. Synthetic resveratrol is available, but it is extremely expensive, about $250.00 per gram.
Other plant sources of resveratrol include grapes or wine (Vitus vinfera), which contains 1-13 mg. of resveratrol per liter, with an average of about 5 mg./liter. Clearly a safer and higher yielding source of resveratrol is Polygonum cuspidatum, since fairly large amounts can be obtained in pill form with the concentrated extract.
Resveratrol is also present in the following plants; Polygonum multiflorum, Pterolobium hexapetallum, Cassia garrettiana Carib, Cassia quinquangulata, Arachis hypogaea, Eucalyptus globulus, and Bauhinia racemosa Lamk, Veratrum grandiflorum, and Veratrum formosanum.
While resveratrol is perhaps the most widely studied of the constituents in Polygonum cuspidatum, there are also other active substances contained therein, such as emodin, polydatin, and piceid. These may contribute to the beneficial effects of the plant extract in a synergistic fashion, but also exhibit some of the same and other pharmacological properties as resveratrol.
In general, the amount of ephedrine would be about 20-350 mg. per day, preferably about 25-100 mg. per day. The amount of caffeine or caffeine containing botanical yielding 10-500 mg./day, preferably about 20-200 mg./day. The amount of resveratrol or botanical source of resveratrol would yield from 1-500 mg. per day of actual resveratrol. Other COX-2 inhibitors must be used at a level that significantly inhibits the COX-2 enzyme, or enough to reduce prostaglandin synthesis sufficient to overcome feedback inhibition of the thermogenisis initiated by the noradrenaline stimulating agent. Nicotinic acid or analogues, esters, or pro-drugs of nicotininc acid may optionally be added to the thermogenic daytime formula. The components in the thermogenic triad may be in immediate-release form or sustained-release form. The ingredients are preferably in sustained-release form as this prolongs the metabolic activity and reduces the potential for side-effects that may arise from xe2x80x9cspikingxe2x80x9d or a rapid rise in blood levels of the respective compounds if given in immediate-release form.
The instant invention also includes a growth hormone producing combination of L-arginine or L-ornithine with L-lysine and nicotinic acid (niacin) in a separate dosage form that could be taken at night, or the arginine/lysine combination and niacin could be taken at the same time as the thermogenic formula. The daily dose or nightly dose of arginine and lysine (the dose that would be taken during any 24 hour period) would be from 50 mg. to 30 grams of each amino acid. The daily or nightly (24 hour) dose of niacin would be from 50 mg. to 3 grams. The preferable dose would be about 1.2 grams of L-arginine, 1.2 grams of L-lysine, and 200 to 750 mg. of niacin (nicotinic acid). The same amounts of omithine could be substituted for the arginine. The arginine or ornithine, lysine, and niacin may be in immediate-release form or sustained-release form, but preferably in sustained-release form. The preferred time for administration would be at nighttime.
Alternatively, an ester of arginine or lysine and nicotinic acid could be used for the growth hormone stimulating formulation. Such an ester is arginine nicotinate as described in U.S.Pat. No. 5157022. Likewise, an arginine derivitive compound such as arginine aspartate, arginine alpha ketogluterate, or a di-peptide of arginine such as alanylarginine (ALA-ARG), valinyl-arginine (VAL-ARG), or leucinyl-arginine (LEU-ARG) can be used with L-lysine and the nicotinic acid component. Or tri-peptides containing arginine such as argininyl-lysinyl-glutamic acid (ARG-LYS-GLU) and arginyl-glysyl-arginine (ARG-GLY-ARG) can be combined with L-lysine and nicotinic acid.
As mentioned above, any of these arginine, lysine, or ornithine, derivative compounds or salts can be combined with esters or pro-drugs of nicotinic acid such as acipimox, beta-pyridylcarbinol, mesoinositol-hexanicotinate, xantinol nicotinate or other like compounds or derivatives of nicotinic acid.
Furthermore, recombinant human growth hormone or bovine growth hormone, both of which must be injected, can be used in conjunction with L-lysine and nicotinic acid or its esters or prodrugs such as arginine nicotinate, to enhance weight loss in obese subjects. However, the preferable route of administration would be oral, the composition; L-arginine hydrochloride, L-lysine hydrochloride, and nicotinic acid, and in sustained-release form.
Useful dosage forms include without limitation oral forms such as tablets, capsules, beads, granules, aggregates, powders, gels, liquids, solids, semi-solids, and suspensions. Lotions, transdermal delivery systems, including dermal patches, aerosols or nasal mists, suppositories, salves and ointments are also useful.
A variety of additives can be incorporated into the inventive compositions for their intended functions. These additives are usually used in small amounts.
Useful additives include, for example, gelatin, vegetable proteins such as sunflower protein, soybean proteins, cotton seed proteins, peanut proteins, rape seed proteins, blood proteins, egg proteins, acrylated proteins; water-soluble polysaccharides such as alginates, carrageenans, guar gum, agar-agar, gum arabic, and related gums (gum ghatti gum karaya, gum tragacanth), pectin; water-soluble derivatives of cellulose: alkylcelluloses, hydroxyalkylcelluloses and hydroxyalkylalkylcelluloses, such as methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxpropylmethylceflulose, hydroxbutylmethylcellulose, cellulose esters and hydroxyalkylcellulose esters such as: cellulose acetate phthalate (CAP), carboxyalky I celluloses, carboxyalkylalkylcelluloses, carboxyalkylcellulose esters such as carboxymethyl cellulose and their alkali metal salts; water-soluble synthetic polymers such as polyacrylic acids and polyacrylic acid esters, polymethacrylic acids and polymethacrylic acid esters, polyvinylacetates, polyvinylalcohols, polyvinylacetatephthalates (PVAP), polyvinylpyrrolidone (PVP), PVP/vinyI acetate copolymer, and polycrotonic acids; also suitable are phthalated gelatin, gelatin succinate, crosslinked gelatin, shellac, water-soluble chemical derivatives of starch, cationically modified acrylates and methacrylates possessing, for example, a tertiary or quaternary amino group, such as the diethylan-finoethyl group, which may be quatemized if desired; and other similar polymers.
Processing aids such as sucrose, polydextrose, maltodextrin, lactose, maltose, stearic acid, microcrystalline cellulose, and the like may also be used. Examples of classes of additives include excipients, lubricants, oils, hydrocolloid suspending agents, buffering agents, disintegrating agents, stabilizers, foaming agents, pigments, coloring agents, fillers, bulking agents, sweetening agents, flavoring agents, fragrances, release modifiers, ect.
Sustained release within the scope of this invention can be taken to mean any one of a number of extended release dosage forms. The following terms may be considered to be substantially equivalent to sustained release, for the purposes of the present invention: continuous release, sustained release, delayed release, depot, gradual release, long-term release, programmed release, prolonged release, proportionate release, protracted release, repository, retard, slow release, spaced release, sustained release, time coat, timed release, delayed action, extended action, layered-time action, long acting, prolonged action, repeated action, slowing acting, sustained action, sustained-action medications, and extended release. Further discussions of these terms may be found in Lesczek Krowczynski Extended-Release Dosage Forms, 1987 (CRC Press, Inc.).
The various sustained release technologies cover a very broad spectrum of drug dosage forms. Sustained release technologies include, but are not limited to physical systems and chemical systems. Physical systems include, but not limited to, reservoir systems with rate-controlling membranes, such as microencapsulation, macroencapsulation, and membrane systems; reservoir systems without rate-controlling membranes, such as hollow fibers, ultra microporous cellulose triacetate, and porous polymeric substrates and foams; monolithic systems, including those systems physically dissolved in non-porous, polymeric, or elastomeric matrices (e.g., non-erodible, erodible, environmental agent ingression, and degradable), and materials physically dispersed in non-porous, polymeric, or elastomeric matrices (e.g., non-erodible, erodible, environmental agent ingression, and degradable); laminated structures, including reservoir layers chemically similar or dissimilar to outer control layers; and other physical methods, such as osmotic pumps, or adsorption onto ion-exchange resins.
Chemical systems include, but are not limited to, chemical erosion of polymer matrices (e.g., heterogeneous, or homogeneous erosion), or biological erosion of a polymer matrix (e.g., heterogeneous, or homogeneous).
Hydrogels may also be employed as described in xe2x80x9cControlled Release Systems: Fabrication Technologyxe2x80x9d, Vol. 11, Chapter 3; p 41-60; xe2x80x9cGels For Drug Deliveryxe2x80x9d, Edited By Hsieh, D.
Sustained release drug delivery systems may also be categorized under their basic technology areas, including, but not limited to, rate-preprogrammed drug delivery systems, activation-modulated drug delivery systems, feedback-regulated drug delivery systems, and site-targeting drug delivery systems.
Furthermore, compositions according to the invention may be administered or coadministered with conventional pharmaceutical binders, excipients and additives. Many of these are sustained-release polymers which can be used in sufficient quantities to produce a sustained-release effect. These include, but are not limited to, gelatin, natural sugars such as raw sugar or lactose, lecithin, mucilage, plant gums, pectin""s or pectin derivatives, algal polysaccharides, glucomannan, agar and lignin, guar gum, locust bean gum, acacia gum, xanthan gum, carrageenan gum, karaya gum, tragacanth gum, ghatti gum, starches (for example corn starch or amylose), dextran, polyvinyl pyrrolidone, polyvinyl acetate, gum arabic, alginic acid, tylose, talcum, lycopodium, silica gel (for example colloidal), cellulose and cellulose derivatives (for example cellulose ethers, cellulose ethers in which the cellulose hydroxy groups are partially etherified with lower saturated aliphatic alcohols and/or lower saturated, aliphatic oxyalcohols, for example methyl oxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose phthalate, cross-linked sodium carboxymethylcellulose, cross-linked hydroxypropylcellulose, high-molecular weight hydroxymethylpropycellulose, carboxymethyl-cellulose, low-molecular weight hydroxypropylmethylcellulose medium-viscosity hydroxypropylmethylcellulose hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcelulose, alkylcelluloses, ethyl cellulose, cellulose acetate, cellulose propionate (lower, medium or higher molecular weight), cellulose acetate propionate, cellulose acetate butyrate, cellulose triacetate, methyl cellulose, hydroxypropyl cellulose, or hydroxypropylmethyl cellulose), fatty acids as well as magnesium, calcium or aluminum salts of fatty acids with 12 to 22 carbon atoms, in particular saturated (for example stearates such as magnesium stearate), polycarboxylic acids, emulsifiers, oils and fats, in particular vegetable (for example, peanut oil, castor oil, olive oil, sesame oil, cottonseed oil, corn oil, wheat germ oil, sunflower seed oil cod liver oil, or high melting point hydrogenated vegetable oil such as can be produced from soy beans); glycerol esters and polyglycerol esters of saturated fatty acids C12H24O2 to C18J36O2 and their mixtures, it being possible for the glycerol hydroxy groups to be totally or also only partly esterified (for example mono-, di- and triglycerides); pharmaceutically acceptable mono- or multivalent alcohols and polyglycols such as polyethylene glycol and derivatives thereof, esters of aliphatic saturated or unsaturated fatty acids (2 to 22 carbon atoms, in particular 10-18 carbon atoms) with monovalent aliphatic alcohols (1 to 20 carbon atoms) or multivalent alcohols such as glycols, glycerol diethylene glycol pentacrythritol, sorbitol mannitol and the like, which may optionally also be etherified, esters of citric acid with primary alcohols, acetic acid, urea, benzyl benzoate, dioxolanes, glyceroformals, tetrahydrofurfuryl alcohol polyglycol ethers with C1-C12-alcohols, dimethylacetamide, lactamides, lactates, ethylcarbonates, silicones (in particular medium-viscous polydimethyl siloxanes), calcium carbonate, sodium carbonate, calcium phosphate, sodium phosphate, magnesium carbonate and the like.

Methods and compositions for producing weight loss