Patent Application
20100286004
The invention relates to lubricant oil additive compositions and lubricating oil compositions containing the same. More particularly, this invention relates to combinations of hindered phenolic antioxidants, boronated hindered phenolic antioxidants, alkylated diphenylamines and organomolybdenum compounds useful as lubricant oil compositions and lubricating oil additive compositions.
Hindered phenolic and boronated hindered phenolics are well known in the art, including large molecular phenolics incorporating the moiety, 2,6-di-tert-butylphenol, and the like. See, for example, the following US and foreign patents: U.S. Pat. No. 4,927,553; U.S. Pat. No. 3,356,707; U.S. Pat. No. 3,509,054; U.S. Pat. No. 3,347,793; U.S. Pat. No. 3,014,061; U.S. Pat. No. 3,359,298; U.S. Pat. No. 2,813,830; U.S. Pat. No. 2,462,616; GB 864,840; U.S. Pat. No. 5,698,499; U.S. Pat. No. 5,252,237; US RE 32,295; U.S. Pat. No. 4,547,302; U.S. Pat. No. 3,211,652; and U.S. Pat. No. 2,807,653
The use of alkylated diphenylamine as an antioxidant additive in lubricating oil formulations is also well known in the art. See, for example, the following US patents: U.S. Pat. No. 5,620,948; U.S. Pat. No. 5,595,964; U.S. Pat. No. 5,569,644; U.S. Pat. No. 4,857,214; U.S. Pat. No. 4,455,243; and U.S. Pat. No. 5,759,965.
There are many examples in the patent literature showing the use of molybdenum additives as antioxidants, deposit control additives, anti-wear additives and friction modifiers. See, for example, the following US and foreign patents: U.S. Pat. No. 5,840,672; U.S. Pat. No. 5,814,587; U.S. Pat. No. 4,529,526; WO 95/07966; U.S. Pat. No. 5,650,381; U.S. Pat. No. 4,812,246; U.S. Pat. No. 5,458,807; WO 95/07964; U.S. Pat. No. 5,880,073; U.S. Pat. No. 5,658,862; U.S. Pat. No. 5,696,065; WO 95/07963; U.S. Pat. No. 5,665,684; U.S. Pat. No. 4,360,438; U.S. Pat. No. 5,736,491; WO 95/27022; U.S. Pat. No. 5,786,307; U.S. Pat. No. 4,501,678; U.S. Pat. No. 5,688,748; EP 0 447 916 A1; U.S. Pat. No. 5,807,813; U.S. Pat. No. 4,692,256; U.S. Pat. No. 5,605,880; WO 95/07962; U.S. Pat. No. 5,837,657; U.S. Pat. No. 4,832,867; U.S. Pat. No. 4,705,641; EP 0 768 366 A1; U.S. Pat. No. 6,103,674; U.S. Pat. No. 6,010,987; U.S. Pat. No. 6,110,878; EP 1 136 496 A1; U.S. Pat. No. 6,150,309; U.S. Pat. No. 6,232,276; U.S. Pat. No. 6,306,802; EP 1 136 497 A1; U.S. Pat. No. 5,888,945; U.S. Pat. No. 6,187,723; U.S. Pat. No. 6,117,826; U.S. Pat. No. 6,103,674; U.S. Pat. No. 6,063,741; U.S. Pat. No. 6,017,858; U.S. Pat. No. 5,994,277; and U.S. Pat. No. 6,174,842.
The present invention generally provides a lubricant oil composition having improved oxidative stability, the composition comprising at least one hindered phenolic antioxidant, at least one mono-boronated hindered phenolic antioxidant, at least one di-boronated hindered phenolic antioxidant, at least one alkylated diphenylamine, and at least one organomolybdenum compound. The invention also provides a lubricating oil additive concentrate composition that imparts synergistic oxidative stability to a lubricant oil upon its addition, the concentrate composition comprising at least one hindered phenolic antioxidant, at least one mono-boronated hindered phenolic antioxidant, at least one di-boronated hindered phenolic antioxidant, at least one alkylated diphenylamine, and at least one organomolybdenum compound. Further, the concentrate compositions of the present invention may also be prepared with a high concentration of hindered phenolic antioxidants without deleterious effects on viscosity or lubricant solubility.
The synergistic improvement of oxidative stability in lubricant oil compositions and lubricating oil additive concentrate compositions comprising at least one hindered phenolic antioxidant, at least one mono-boronated hindered phenolic antioxidant, at least one di-boronated hindered phenolic antioxidant, and at least one alkylated diphenylamine is disclosed in concurrently filed, commonly owned U.S. Provisional Application 60/758,754 filed on Jan. 13, 2006, and in PCT application number PCT/US2007/060489 that claims priority to U.S. Provisional Application 60/758,754, both of which are hereby incorporated by reference in their entirety to the extent allowed by applicable law. The present invention improves upon the disclosure of U.S. Provisional Application 60/758,754 such that lubricant oil compositions and lubricating oil additive concentrate compositions comprising at least one hindered phenolic antioxidant, at least one mono-boronated hindered phenolic antioxidant, at least one di-boronated hindered phenolic antioxidant, at least one alkylated diphenylamine, and at least one organomolybdenum compound exhibits improved oxidative stability compared to conventional formulations.
In one aspect, a lubricant oil or lubricating oil additive concentrate composition comprising: (a) 4,4′-methylenebis(2,6-di-tert-butylphenol), (b) 4,4′-methylenebis(2,6-di-tert-butylphenol)-mono-(di-alkyl orthoborate), (c) 4,4′-methylenebis(2,6-di-tert-butylphenol)-di-(di-alkyl orthoborate), (d) an alkylated diphenylamine, and (e) an organomolybdenum compound, is an effective antioxidant combination for use in lubricants.
In another aspect, a lubricant oil or lubricating oil additive concentrate composition comprising: (a) a hindered phenolic antioxidant, (b) either a single or multiple ortho-borate ester, or combinations thereof, derived from a hindered phenolic antioxidant, wherein the boron is attached to the hindered phenolic oxygen, (c) an alkylated diphenylamine, and (d) an organomolybdenum compound, is an effective antioxidant combination for use in lubricants.
Hindered phenolics suitable for use in the compositions of the present invention include phenolics incorporating the 2,6-di-tert-butylphenol moiety. A suitable hindered phenolic, which is commercially sold by Albemarle Corporation™ under the trade name Ethanox® 702, is 4,4′methylenebis(2,6-di-tert-butylphenol), hereinafter referred to as MBDTBP, having the structure of Structure I below:
Other suitable hindered phenolics include, 2,4-di-tert-butylphenol, 2,6-di-tert-butylphenol, 6-tert-butyl-ortho-cresol, 2,6-di-isopropylphenol, 2,4-di-sec-butylphenol, higher molecular weight hindered phenolic antioxidants derived synthetically from 2,4-di-tert-butylphenol, 2,6-di-tert-butylphenol, 6-tert-butyl-ortho-cresol, 2,6-di-isopropylphenol, or 2,4-di-sec-butylphenol, butylated hydroxy toluene (BHT), and the like.
The amount of hindered phenolic present in the compositions of the invention ranges from about 1 to about 50 weight percent of the total concentration of hindered phenolic, boronated hindered phenolic, and alkylated diphenylamine. In additional aspects the amount of hindered phenolic present in the compositions of the invention ranges from about 1 to about 40 weight percent, about 1 to about 30 weight percent, about 1 to about 25 weight percent, about 1 to about 20 weight percent, and about 1 to about 15 weight percent of the total concentration of hindered phenolic, boronated hindered phenolic, and alkylated diphenylamine.
The mono- and di-boronated hindered phenolics suitable for use in the compositions of the present invention are derived from the hindered phenolics described above by reaction with tri-alkyl orthoborates. One such process is disclosed in U.S. Pat. No. 4,927,553. In one aspect, suitable mono- and di-boronated hindered phenolics have the structures of Structures II and III below:
wherein R1, R2, R3, and R4 are independently selected from the group consisting of linear, branched and cyclic C1 to C8 alkyl groups. Examples of such groups include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 2-methyl-2-butyl, 3-methyl-2-butyl, isopentyl, n-hexyl, cyclopentyl, cyclohexyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 3-methyl-2-pentyl, 4-methyl-2 pentyl, 3-methyl-3-pentyl, 3,3-dimethylbutyl, 3,3-dimethyl-2-butyl, 2,3-dimethyl-2-butyl, 2-methyl-2-hexyl, 2,2-dimethyl-3-pentyl, 2-heptyl, 3-heptyl, 2-methyl-3-hexyl, 3-ethyl-3-pentyl, 2,3-dimethyl-3-pentyl, 2,4-dimethyl-3-pentyl, 5-methyl-2-hexyl, 4,4-dimethyl-2-pentyl, 5-methylhexyl, n-heptyl, n-octyl, iso-octyl, 2-ethylhexyl, 2-propylpentyl, 2-octyl, 3-octyl, 2,44-trimethylpentyl, 4-methyl-3-heptyl and 6-methyl-2-heptyl.
Other mono- and di-boronated hindered phenolics may be derived from reacting the specific hindered phenolics described above, or mixtures of hindered phenolics, with tri-alkyl orthoborates.
The combined total of mono- and di-boronated hindered phenolics present in the compositions of the invention ranges from about 10 to about 80 weight percent of the total concentration of hindered phenolic, boronated hindered phenolic, and alkylated diphenylamine. The ratio of mono-boronated hindered phenolic to di-boronated hindered phenolic may vary from about 0.01:1 to about 1:0.01. The amount of mono-boronated hindered phenolic can be approximately equal to or greater than that of di-boronated hindered phenolic.
The amount of MBDTBP in conventional lubricant oil additive concentrate compositions has been limited by its solubility to about 10 wt % of the total additive concentrate. However, the present invention provides a method for increasing the concentration of hindered phenolic antioxidant in the lubricant oil additive concentrate composition to be increased to as high as about 50 wt % by including boronated hindered phenolic antioxidants in the lubricant oil additive concentrate composition.
The alkylated diphenylamines suitable for use in the compositions of the present invention are prepared from diphenylamine by reaction with olefins. One particularly useful method of preparing alkylated diphenylamines is described in US Patent Publication US-2006-0276677-A1 (which related to U.S. Ser. No. 11/442,856 filed 30 May 2006, which claims priority to U.S. Provisional Patent Application 60/687,182 filed on Jun. 2, 2005 and to U.S. Provisional Patent Application 60/717,322 filed on Sep. 14, 2005), which US Patent Publication is incorporated in its entirety by reference herein to the extent allowed by applicable law. Both mono- and di-alkylated diphenylamines may be employed, either alone are in combination, and have the structures shown in Structures IV and V below:
wherein R1, R2 and R3 are independently selected from the group consisting of linear, branched and cyclic C4 to C32 alkyl groups. Examples of such groups include, but are not limited to, alkyl groups derived from linear alpha-olefins, isomerized alpha-olefins polymerized alpha-olefins, low molecular weight oligomers of propylene, and low molecular weight oligomers of isobutylene. Specific examples include but are not limited to butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, dipropyl, tripropyl, tetrapropyl, pentapropyl, hexapropyl, heptapropyl, octapropyl, diisobutyl, triisobutyl, tetraisobutyl, pentaisobutyl, hexaisobutyl, and heptaisobutyl.
The combined total of mono- and di-alkylated diphenylamine present in the compositions of the invention ranges from about 10 to about 80 weight percent of the total concentration of hindered phenolic, boronated hindered phenolic, and alkylated diphenylamine. The ratio of mono- to di-alkylated diphenylamine may vary from about 0.01:1 to about 1:0.01.
Examples of suitable alkylated diphenylamines are nonylated diphenylamines (NDPA), octylated diphenylamines, mixed octylated/styrenated diphenylamines (such as Durad® AX55), and mixed butylated/octylated diphenylamines (such as Vanlube® 961). Further, the nitrogen content of the alkylated diphenylamines can be in the range of about 2.0 to about 6.0 wt. %. Lower levels of nitrogen dilute the effectiveness of the alkylated diphenylamines while higher levels of nitrogen may adversely impact compatibility of the alkylated diphenylamines in the lubricant or the lubricant's volatility. The alkylated diphenylamines can be a liquid or low melting solid.
Organomolybdenum compounds suitable for use in the present invention include sulfur-free compounds, phosphorus-free compounds, and sulfur-containing compounds. The molybdenum content of organomolybdenum compounds may vary from about 1 wt % to about 15 wt %. The concentration of the organomolybdenum compound may range from about 1 wt % to about 40 wt % of the total concentration of hindered phenolic, boronated hindered phenolic, alkylated diphenylamine and organomolybdenum compound.
The amount of organomolybdenum compound used in compositions of the present invention is such that the weight ratio of molybdenum to boron ranges from about 0.01:1 to about 10:1. The molybdenum content of a lubricant oil can range from between about 50 to about 1000 ppm and the boron content can range between about 50 to about 500 ppm. The molybdenum content of a lubricant oil can range from between about 100 to about 400 ppm and the boron content can range between about 100 to about 400 ppm.
Sulfur- and phosphorus-free organomolybdenum compounds may be prepared by reacting a sulfur and phosphorus-free molybdenum source with an organic compound containing amino and/or alcohol groups. Examples of sulfur- and phosphorus-free molybdenum sources include molybdenum trioxide, ammonium molybdate, sodium molybdate and potassium molybdate. The amino groups may be monoamines, diamines, or polyamines. The alcohol groups may be mono-substituted alcohols, diols or bis-alcohols, or polyalcohols. As an example, the reaction of diamines with fatty oils produces a product containing both amino and alcohol groups that can react with the sulfur- and phosphorus-free molybdenum source.
Examples of sulfur- and phosphorus-free organomolybdenum compounds suitable for use in the present invention include the following: compounds prepared by reacting certain basic nitrogen compounds with a molybdenum source as defined in U.S. Pat. Nos. 4,259,195 and 4,261,843; compounds prepared by reacting a hydrocarbyl substituted hydroxy alkylated amine with a molybdenum source as defined in U.S. Pat. No. 4,164,473; compounds prepared by reacting a phenol aldehyde condensation product, a mono-alkylated alkylene diamine, and a molybdenum source as defined in U.S. Pat. No. 4,266,945; compounds prepared by reacting a fatty oil, diethanolamine, and a molybdenum source as defined in U.S. Pat. No. 4,889,647; compounds prepared by reacting a fatty oil or acid with 2-(2-aminoethyl)aminoethanol, and a molybdenum source as defined in U.S. Pat. No. 5,137,647; compounds prepared by reacting a secondary amine with a molybdenum source as defined in U.S. Pat. No. 4,692,256; compounds prepared by reacting a diol, diamino, or amino-alcohol compound with a molybdenum source as defined in U.S. Pat. No. 5,412,130; compounds prepared by reacting a fatty oil, mono-alkylated alkylene diamine, and a molybdenum source as defined in European Patent Application EP 1 136 496 A1; and compounds prepared by reacting a fatty acid, mono-alkylated alkylene diamine, glycerides, and a molybdenum source as defined in European Patent Application EP 1 136 497 A1.
Examples of commercial sulfur- and phosphorus-free oil soluble molybdenum compounds are Sakura-Lube 700 from Asahi Denka, and Molyvan 856B and Molyvan 855 from R. T. Vanderbilt Company, Inc.
Molybdenum compounds prepared by reacting a fatty oil, diethanolamine, and a molybdenum source as defined in U.S. Pat. No. 4,889,647 are sometimes illustrated as having one or both of the following structures,
wherein R is a fatty alkyl chain. The exact chemical structure of these materials is not fully known and may in fact be multi-component mixtures of many organomolybdenum compounds.
Sulfur-containing organomolybdenum compounds may be prepared by a variety of methods. One method involves reacting a sulfur and phosphorus-free molybdenum source with an amino group and one or more sulfur sources. Sulfur sources include carbon disulfide, hydrogen sulfide, sodium sulfide and elemental sulfur. Alternatively, the sulfur-containing molybdenum compound may be prepared by reacting a sulfur containing molybdenum source with an amino group or thiuram group and optionally a second sulfur source. Examples of sulfur- and phosphorus-free molybdenum sources include molybdenum trioxide, ammonium molybdate, sodium molybdate, potassium molybdate and molybdenum halides. The amino groups may be monoamines, diamines, or polyamines. As an example, the reaction of molybdenum trioxide with a secondary amine and carbon disulfide produces molybdenum dithiocarbamates. Alternatively, the reaction of (NH4)2Mo3S13.n(H2O) where n varies between 0 to 2 with a tetralkylthiuram disulfide produces a trinuclear sulfur-containing molybdenum dithiocarbamate.
Examples of sulfur-containing organomolybdenum compounds suitable for use in the present invention include the following: compounds prepared by reacting molybdenum trioxide with a secondary amine and carbon disulfide as defined in U.S. Pat. Nos. 3,509,051 and 3,356,702; compounds prepared by reacting a sulfur-free molybdenum source with a secondary amine, carbon disulfide, and an additional sulfur source as defined in U.S. Pat. No. 4,098,705; compounds prepared by reacting a molybdenum halide with a secondary amine and carbon disulfide as defined in U.S. Pat. No. 4,178,258; compounds prepared by reacting a molybdenum source with a basic nitrogen compound and a sulfur source as defined in U.S. Pat. Nos. 4,263,152, 4,265,773, 4,272,387, 4,285,822, 4,369,119, and 4,395,343; compounds prepared by reacting ammonium tetrathiomolybdate with a basic nitrogen compound as defined in U.S. Pat. No. 4,283,295; compounds prepared by reacting an olefin, sulfur, an amine and a molybdenum source as defined in U.S. Pat. No. 4,362,633; compounds prepared by reacting ammonium tetrathiomolybdate with a basic nitrogen compound and an organic sulfur source as defined in U.S. Pat. No. 4,402,840; compounds prepared by reacting a phenolic compound, an amine and a molybdenum source with a sulfur source as defined in U.S. Pat. No. 4,466,901; compounds prepared by reacting a triglyceride, a basic nitrogen compound, a molybdenum source, and a sulfur source as defined in U.S. Pat. No. 4,765,918; compounds prepared by reacting alkali metal alkylthioxanthate salts with molybdenum halides as defined in U.S. Pat. No. 4,966,719; compounds prepared by reacting a tetralkylthiuram disulfide with molybdenum hexacarbonyl as defined in U.S. Pat. No. 4,978,464; compounds prepared by reacting an alkyl dixanthogen with molybdenum hexacarbonyl as defined in U.S. Pat. No. 4,990,271; compounds prepared by reacting alkali metal alkylxanthate salts with dimolybdenum tetra-acetate as defined in U.S. Pat. No. 4,995,996; compounds prepared by reacting (NH4)2Mo3S13.2(H2O) with an alkali metal dialkyldithiocarbamate or tetralkyl thiuram disulfide as define in U.S. Pat. No. 6,232,276; compounds prepared by reacting an ester or acid with a diamine, a molybdenum source and carbon disulfide as defined in U.S. Pat. No. 6,103,674; and compounds prepared by reacting an alkali metal dialkyldithiocarbamate with 3-chloropropionic acid, followed by molybdenum trioxide, as defined in U.S. Pat. No. 6,117,826.
Examples of commercial sulfur-containing oil soluble molybdenum compounds are Sakura-Lube® 100, Sakura-Lube® 155, Sakura-Lube® 165, and Sakura-Lube® 180 from Asahi Denka Kogyo K. K., Molyvan® A, Molyvan® 807 and Molyvan® 822 from R. T. Vanderbilt Company, and Naugalube® MolyFM from Crompton Corporation.
Molybdenum dithiocarbamates are suitable organomolybdenum compounds and have the following structure:
wherein R is independently selected from hydrogen or an alkyl group containing 4 to 18 carbons, and X is independently selected from oxygen or sulfur.
The lubricating oil may be any basestock or base oil (characterized as Group I, Group II, Group III, Group IV or Group V as defined by the API basestock classification system), or lubricant composed predominately of aromatics, naphthenics, paraffinics, poly-alpha-olefins and/or synthetic esters. Further, the lubricant may also contain additional additives so as to make the system acceptable for use in a variety of applications. These additives include dispersants, detergents, viscosity index improvers, pour point depressants, anti-wear additives, extreme pressure additives, friction modifiers, corrosion inhibitors, rust inhibitors, emulsifiers, demulsifiers, anti-foaming agents, colorants, seal swelling agents, and additional antioxidants.
The present invention may be useful in passenger car engine oils, heavy duty diesel oils, medium speed diesel oils, railroad oils, marine engine oils, natural gas engine oils, 2-cycle engine oils, steam turbine oils, gas turbine oils, combined cycle turbine oils, R&O oils, industrial gear oils, automotive gear oils, compressor oils, manual transmission fluids, automatic transmission fluids, slideway oils, quench oils, flush oils and hydraulic fluids. Suitable applications are in engine oils. A suitable application is in low phosphorus engine oils characterized by a phosphorus content of less than 1000 ppm.
The lubricating oil additive concentrate may or may not contain a diluent oil. If a diluent oil is used, the diluent oil is typically present between 1 and 80 wt. % of the concentrate.
Typically, the total amount of hindered phenolic, boronated hindered phenolic, alkylated diphenylamine, and organomolybdenum compound that are added to fully formulated oils depends upon the end use application. For example, in a turbine oil the total amount of hindered phenolic, boronated hindered phenolic, alkylated diphenylamine, and organomolybdenum compound added to the oil ranges between about 0.05 and about 1.0 wt. %. In contrast, in an engine oil the total amount of hindered phenolic, boronated hindered phenolic, alkylated diphenylamine and organomolybdeum compound added to the oil ranges between about 0.2 and about 3.0 wt. %. In ultra-low phosphorus engine oils the total amount of hindered phenolic, boronated hindered phenolic, and alkylated diphenylamine may approach 5.0 wt. % or more.
An example of a lubricating oil additive concentrate in accordance with the present invention is as follows:
An example of a low phosphorus engine oil in accordance with the present invention is as follows:
A passenger car engine oil preblend was prepared in accordance with the present invention by blending the following materials:
The oxidative stability of these finished engine oils was evaluated in a bulk oil oxidation test. Each oil (300 mL) was treated with an iron naphthenate oxidation catalyst to deliver 110 ppm of iron to the finished oil. The oils were heated in a block heater at 150° C., while 10 liters/hour of dry oxygen was bubbled through the oil. Samples of the oxidized oils were removed at 24, 48, 72, 96, 120, 144, 168 and 192 hours. Kinematic viscosities of each sample were determined at 40° C. The percent viscosity increase of the oxidized oil versus the fresh oil was calculated. The percent viscosity increase results are shown in Table 2.
A higher percent viscosity increase is a measure of increased oxidation and degradation of the lubricant. These results clearly show that the inventive antioxidant combination in Examples A.3 to A.6 provide superior oxidation protection compared to the other Examples (A.1-A.2). Antioxidant systems that do not contain the combination of 4,4′-methylenebis(2,6-di-tert-butylphenol), boronated 4,4′-methylenebis(2,6-di-tert-butylphenol), nonylated diphenylamine and organomolybdenum compound show poor oxidation control while systems containing BMBDTBP, NDPA and MoDTC show superior oxidative control. These results are shown graphically in
The oxidative stability of the finished engine oils prepared in Example A was evaluated using pressurized differential scanning calorimetry following the ASTM standard test method D 6186 and using the following operation conditions: isothermal temperature=180° C., oxygen gas @ 500 psig with a flow rate of 100 mL/min, approximately 3 mg sample size, open aluminum pans. Each oil was treated with an iron naphthenate oxidation catalyst to deliver 55 ppm of iron to the finished oil. Oxidation induction times (OIT) were determined according to the ASTM method. Each oil was tested in duplicate and the results averaged. The OIT results are shown in Table 3.
A longer induction time is a measure of increased oxidation stability of the lubricant. These results clearly show that the inventive antioxidant combination in Examples A.4 to A.6 provide superior oxidation protection compared to the non-inventive Examples (A.1-A.2). Antioxidant systems that do not contain the combination of 4,4′-methylenebis(2,6-di-tert-butylphenol), boronated 4,4′-methylenebis(2,6-di-tert-butylphenol), nonylated diphenylamine and molybdenum show poor oxidation control while systems containing BMDTBP, NDPA and MoDTC show superior oxidative control. Also, considerably less, i.e. 25% less, antioxidant is used in inventive oil A.3 versus non-inventive oil A.2 in order to deliver the same performance level in the PDSC (112.12 minutes and 110.77 minutes statistically equivalent).
While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions, methods and/or processes and in the steps or in the sequence of steps of the methods described herein without departing from the concept and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the scope and concept of the invention.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US07/65371 | 3/28/2007 | WO | 00 | 9/25/2008 |
| Number | Date | Country | |
|---|---|---|---|
| 60787334 | Mar 2006 | US |
