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Discusses a study on polyethylene glycol ingredients (PEG) which are being used in cosmetics. Attributes of PEG that are important to a cosmetic formulator; Details of pH and viscosity of the ingredients; Method used to test the foaming impact of PEG.

This study performs tests of the random walk hypothesis for international commercial real estate markets utilizing stock market indices of real estate share prices for three geographical regions: Europe, Asia and North America. The augmented Dickey-Fuller and Phillips-Perron unit root tests and Cochrane variance ratio test find that each of these markets (as well as associated broader stock markets) exhibits random walk behavior. Moreover, a non-parametric runs test provides support for weak-form market efficiency in the real estate markets. In addition, Johansen-Juselius co-integration analysis reveals that all three markets appear co-integrated and share a common long-run stochastic trend. Results of co-integration analyses and vector error correction models suggest that diversification benefits through international real estate securities can only be achieved in the short run.

Lesquerolic acid was and a,O-diol esters were synthesized via immobilizedRhizomucor mieheilipase-(Lipozyme) catalyzed esterification of lesquerolic acid and alcoholysis of lesquerella oil. For each wax ester synthesis, when alcohol substrate was present at a slight (ca. 20%) stoichiometric excess and water content was kept low, over 94% of the hydroxy acyl groups were esterified. The extent of reaction and the ratio of monoester to diester produced for a,O-diol reactions was controlled by the solubility of diol in the medium. This latter quantity increased as alcoholysis proceeded due to the formation of partial glycerides and monoesters, which increased the polarity of the medium. Alcoholysis reactions were significantly slower when the medium diol content was above saturation. As the diol chainlength increased, diol solubilization decreased, the ratio of monoester to diester decreased, and the extent of hydrolysis increased. Alcoholysis reactions involving either fatty alcohols or diols suffered from acyl migration, which lowered the purity of lesquerolic acid esters. Several lesquerolic acid esters, synthesized on a preparative scale and purified via column chromatography, were evaluated for their properties: density, viscosity, and melting point. Potential applications for lesquerolic acid esters are discussed.

Estolides produced from an acid-catalyzed condensation of oleic acid were characterized by high-performance liquid chromatography (HPLC), gas chromatography (GC), GC-mass spectrometry (MS) and nuclear magnetic resonance (NMR). C-8 reverse-phase HPLC provided a clean resolution of the estolide oligomers present in the reaction mixtures, allowing an average oligomier distribution to be calculated. Corroboration of HPLC results were obtained either through hydrolysis of the estolide mixture and quantitation of the hydroxy fatty acid content by GC, through the integration of the a-methylene protons adjacent to the carbonyl of the acids vs. the esterns in the1H NMR spectrum, or by titration of the carboxylic acid with standardized base. GC and GC-MS analysis of the hydrolyzed estolide mixture indicated that the ester position were centered around the original double-bond position, with linkages ranging from positions 5–13. Likewise, the unsaturation was distributed along the fatty acid backbone.

Abstract: Estolides are formed when the carboxylic acid group of one fatty acid forms an ester link at the site of unsaturation of another fatty acid. These compounds have the potential to be used in a variety of applications, such as lubricants, greases, plastics, inks, cosmetics, and surfactants. By manipulating the reaction equilibrium, yields of 20% estolide in clay-catalyzed estolide reactions have been increased to 30%. Reactions conducted at 180C, where water was vented out of the reactor at specific times, not only gave dimer-free estolides but also yields up to 30%. Steam has also been used instead of water with similar results. Estolides were quite stable at temperatures up to 250C, even when they were exposed to air.

Abstract: Meadowfoam fatty acids (83% monoenoic fatty acid), reacted with 0.01–0.1 mole equivalents of perchloric acid, gave 33–71% yield of estolide, an oligomeric 2 ester, resulting from self condensation. Equimolar amounts of perchloric acid to fatty acid failed to produce estolide but converted the fatty acids to a mixture of lactones, mainly γ-eicosanolactone. Temperature plays a critical role; higher temperatures (75–100C), at the same acid concentration, provide lactones while lower temperatures (20–65C) yield estolides. Lower acid levels (<0.1 mole equivalents) gave the best yields (≈70%) at 65C. The estolide and monomer were characterized by nuclear magnetic resonance, infrared high-pressure liquid chromatography, gas chromatography, gas chromatography/mass spectrometry. The estolide is a mixture of oligomers with an average distribution near 1.65 ester units. The ester linkages are located mainly at the original double bond positions but have some positional isomerization to adjacent sites in accord with carbocation migration along the alkyl chain. The residual double bond of the estolide was extensively isomerized fromcis totrans and positionally along the chain. The distilled monomer is similar in structure to the unsaturated portion of the estolide with geometrical and positional double bond isomerization. In addition, a significant amount of cyclization of the fatty acids to lactone (≈30%) had occurred.

Abstract: The lipolysate from immobilizedRhizomucor miehei lipase (Lipozymetm)-catalyzed hydrolysis of lesquerella oil contains typically 35% free fatty acid (FFA), 2% monoglyceride, 25% diglyceride (DG), and 38% triglyceride (TG). Of the FFA, 75–80% are hydroxy acids (HFA). Various methods for isolating HFA from the lipolysate were examined, and a novel saponification/extraction method was developed. Lipolysate was mixed with 4 vol equivalents each of KOH/phosphate buffer and polar organic solvent. Hexane was then added to enhance phase separation. Three phases formed: a lower aqueous phase containing nothing of interest, a polar organic solvent middle phase that contained mostly fatty acid soaps, and a hexane-rich upper phase that contained mostly DG and TG, which can be recycled to a relipolysis step. The middle phase, when treated with concentrated hydrochloric acid, NaCl-saturated water, and hexane, released the FFA into the hexane. This fraction, referred to as the “Product” contained >99% of the FFA released in the lipolysis. “Product” consisted of 85–90% FFA, of which 75–80% was HFA. The other 10–15% of the “Product” consisted of partial glycerides and TG. The most critical parameters for the extraction are the pH of the aqueous solution and the polarity of the organic solvent (acetone was found to be the best choice). Additional purification steps for the “Product” are discussed.

Lesquerella gordonii(Gray) Wats andLimnanthes albaBenth. (Meadowfoam) are species being studied as new and alternative crops. Triglyceride oil from lesquerella contains 55–60% of the uncommon 14-hydroxy-cis-11-eicosenoic acid. Meadowfoam oil has 95% uncommon acids, includingca.60%cis-5-eicosenoic acid. Both oils are predominantly unsaturated (3% saturated acids), and have similar iodine values (90–91), from which oxirane values of 5.7% are possible for the fully epoxidized oils. Each oil was epoxidized withm-chloro-peroxybenzoic acid, and oxirane values were 5.0% (lesquerella) and 5.2% (meadowfoam). The epoxy acid composition of each product was examined by gas chromatography of the methyl esters, which showed that epoxidizedL. gordoniioil contained 55% 11,12-epoxy-14-hydroxyeicosanoic acid, and epoxidized meadowfoam oil contained 63% 5,6-epoxyeicosanoic acid, as expected for normal complete epoxidation. Mass spectrometry of trimethylsilyloxy derivatives of polyols, prepared from the epoxidized esters, confirmed the identity of the epoxidation products and the straightforward nature of the epoxidation process. Synthesis and characterization of these interesting epoxy oils and derivatives are discussed.

Oleic acid, when treated with 1.0 equivalent of perchloric acid at 50°C, produced a 76% yield of polyestolide. The concentration of mineral acid greatly affected the rate of estolide formation, with increased rates under high acid concentrations. Over a range of temperatures from room temperature to 100°C, reaction rates increased at higher temperatures. However, high acid concentrations and temperatures produced undesirable side products, primarily lactones. Other acids catalyze the condensation of oleic acid to form estolide with the following relative rates: HClO4>H2SO4>p-toluenesulfonic>BF3·Et2O> montmorillonite K-10>HCl>H3PO4, HNO3. Addition of water impedes the formation of estolide.

Estolides were produced from meadowfoam oil fatty acids, oleic, linoleic, petroselinic, andcis-5,cis-13 docosadienoic acids. Estolide reaction mixtures were quantitated by Fourier transform infrared spectroscopy and compared to the area percentages determined by high-performance liquid chromatography. The absorbance frequency of estolide carbonyl (1737 cm-1) is different than the lactone carbonyl (1790 cm-1) and the acid carbonyl (1712 cm-1). Estolide standards were obtained by wiped-film molecular-still distillations and column chromatography.

Eight lipases were screened for their ability to synthesize estolides from a mixture that contained lesquerolic (14-hydroxy-11-eicosenoic) acid and octadecenoic acid. With the exception ofAspergillus nigerlipase, all 1,3-specific enzymes (fromRhizopus arrhizusandRhizomucor mieheilipases) were unable to synthesize estolides.Candida rugosaandGeotrichumlipases catalyzed estolide formation at >40% yield, with >80% of the estolide formed being monoestolide from one lesquerolic and one octadecenoic acyl group:Pseudomonassp. lipase synthesized estolides at 62% yield, but the product mixture contained significant amounts of monoestolide with two lesquerolic acyl groups as well as diestolide. ImmobilizedR. mieheilipase was chosen to catalyze the esterification of mono-and polyestolide, derived synthetically from oleic acid, with fatty alcohols or a,?-diols. Yields were >95% for fatty alcohol reactions and >60% for diol reactions. In addition, the estolide linkage remained intact through the course of the esterification process. Esterification of estolides improved the estolide’s properties—for example, lower viscosity and higher viscosity index—but slightly raised the melting point. Estolides and, particularly, estolide esters may be suitable as lubricants or lubricant additives.

Supercritical fluid chromatography (SFC) with an open tubular column of nonpolar stationary phase separated triglycerides from crambe, meadowfoam,Euphorbia lagascae, and vernonia oils based on their molecular weight. The triglyceride compositions were consistent with the literature. SFC proved also to be a valuable tool in analyzing lipase-catalyzed transesterification reactions where lesquerella oil and estolides were among the substrates employed. Analyte molecular weights could be estimated from a retention time- (or elution density-) molecular eeight calibration curve. An increase in isothermal column temperature during SFC pressure or density programming improved the resolution of high-molecular-weight (>600 Da) analytes but yielded poorer resolution for analytes of molecular weight <200. A simultaneous pressure and temperature ramping program proved superior in enhancing resolution in several instances.

Nasturtium (Tropaeolum majusL.) oil contains the highest levels of erucic acid of known seed oils (75–80%). A significant portion of the acid is attached to the 2-position of the glycerol, and trierucin is a major component (ca.50%) of the oil. Seeds from eleven varieties of commercially available garden nasturtium (T. majus) were screened for oil content, erucic acid levels and fatty acid distribution. Oil contents ranged fromca.6 to 11%, and erucic acid levels in the oils ranged from 62 to 80%. One sample ofT. speciosumwas also analyzed, and contained 28% oil, fatty acids from C16to C28and triglycerides up to C72.

Three types of reaction systems, all batch-mode, were employed for production of hydroxy (lesquerolic and auricolic) fatty acidsvia1,3-specific lipolysis ofLesquerella fendlerioil: “Free”Rhizopus arrhizusor immobilizedRhizomucor mieheilipase (Lipozyme™) in reverse micelles (System 1), Lipozyme suspended in lesquerella oil/isooctane mixture (System 2) and a suspension of water and freeR. mieheilipase in lesquerella oil/isooctane (System 3). The objective was to find the system that best maximized yield (i.e., percent hydrolysis), the proportion of hydroxy acids among the free acids liberated (hydroxy acid “purity”), and recovery/reuse of lipase activity, and that could be easily adapted into a large-scale process. System 1 provided the largest percent hydrolysis (55%) and hydroxy acid purity (85%), but of the three systems would be the most difficult to scale up. Thus, System 1 would be the most desirable reaction system only when small batch sizes are to be processed. System 3 yielded 47.2% hydrolysis, but the hydroxy acid purity was at most 73%, making it the least desirable of the three systems to employ. System 2 yielded moderate extents of hydrolyses (30–40%) and large hydroxy acid purity initially (80–83%), but the purity decreased slightly in the latter stages of the reaction due to acyl migration. System 2 was the system most easily adaptable to a large-scale process, making it the method of choice. For System 2 reactions, only when the medium was initially saturated with water and water consumed by the reaction was continuously replaced could 30–40% hydrolysis be achieved. External mass transfer limitations for Lipozyme-catalyzed reactions were not present when the solution’s water content was not above saturation, and its kinematic viscosity, controlled by the temperature and the proportion of isooctane, was below 41 centistokes.

The formation of estolides was detected during the studies on dimerization of meadowfoam oil fatty acids. By adjusting the reaction conditions, it was possible to produce monoestolides with little dimer or trimer formations. Estolides have potential use in lubricant, cosmetic and ink formulations and in plasticizers. This paper reports the conditions for production of estolides from mixed meadow-foam fatty acids, commercial oleic acid, high-oleic sun-flower oil fatty acids,cis-5,cis-13-docosadienoic acid, petroselinic acid and linoleic acid.

This paper examines the attractiveness of the equity portfolios of life insurance companies as an alternative investment to mutual funds. In particular, this study analyzes the risk-adjusted investment performance of the stock portfolios of life insurance companies, attributable to their stock selection and market timing abilities. Using conventional measures of risk-adjusted portfolio performance, we find that life insurance companies exhibit performance similar to mutual funds. The evidence suggests that the life insurance companies, like their mutual fund counterparts, fail to exhibit differential stock selection or market timing abilities that are statistically significant. While the risk-adjusted investment performance of the two investment vehicles is similar, the variable annuity contracts of life insurance companies may offer an edge over mutual funds due to their ability to defer taxes.

Simulation of commercial processing of Cuphea seed to obtain needed quantities of oil and meal was accomplished with pilot facilities. Cuphea seed was conditioned in a single-deck cooker. Cooked seed was pressed with a mechanical screw with two-speed shaft, variable-speed drives and a four-section cage with cored sleeves. A feed rate of 22 kg seed/h and a feed screw-to-main shaft ratio of 2:1 gave good press cake with 8.1% residual oil. Press cake was extracted in a batch-type modular extraction pilot plant. Miscella stages were sequentially pumped through the beds, followed by hexane rinses. Spent cake was desolventized and toasted, and full miscellas were stripped to recover the crude oil. The finished Cuphea meal had only 0.30–0.55% residual oil. Thus, conditioned Cuphea seed was easily pressed without prior flaking to acceptable cakes, and conditions simulating commercial solvent extraction efficiently removed residual cake oil.

A lesquerella species (Lesquerella fendleri) being investigated as a domestic source of seed oil containing hydroxy fatty acids shows good agronomic properties and is being tested in semi-commercial production.Lesquerella fendleriseeds contain 25% oil, of which 55% is lesquerolic acid (14-hydroxy-cis-11-eicosenoic). Oils produced in pilot-plant quantities by screw press, prepress-solvent extraction and extrusion-solvent extraction processes have been refined in the laboratory by filtering, degumming and bleaching. Two American Oil Chemists’ Society (AOCS) standard bleaching earths and two commercial earths were compared for effectiveness in bleaching these dark, yellow-red, crude lesquerella oils. Free fatty acids (1.3%), iodine value (111), peroxide value (<4 meq/kg), unsaponifiables (1.7%) and hydroxyl value (100) were not significantly affected by degumming and bleaching, but phosphorus levels of 8–85 ppm in the crude oils were reduced to 0.5–1.1 ppm in the degummed and bleached oils. Crude oils had Gardner colors of 14, which were reduced to Gardner 9–11 in the degummed and bleached oil, depending on bleach type and quantity used. AOCS colors in the range of 21–25R 68–71Y were obtained. By including charcoal in the bleaching step, a considerably lighter oil could be obtained (Gardner 7).

This report examines the use of lipases for isolating fatty acids with ?5 unsaturation from the seed oil ofLimnanthes alba, or meadowfoam. Seven lipase types and three enzyme configurations (immobilized, “free” and reversemicellar encapsulated) were examined. All lipases discriminated against ?5 acids to varying degrees, but the degree of discrimination was independent of enzyme configuration. Lipase-catalyzed esterification of meadowfoam oil’s free fatty acids was much more successful for isolating ?5 acyl groups than was lipolysis. For example, esterification directed byChromobacterium viscosumlipase yielded a free fatty acid product containing >95% of the ?5 acyl groups at >99% purity.

Abstract: A lesquerella species (Lesquerella fendleri) being investigated as a domestic source of seed oil containing hydroxy fatty acids shows good agronomic properties and is being tested in semi-commercial production.Lesquerella fendleri seeds contain 25% oil, of which 55% is lesquerolic acid (14-hydroxy-cis-11-eicosenoic). Oils produced in pilot-plant quantities by screw press, prepress-solvent extraction and extrusion-solvent extraction processes have been refined in the laboratory by filtering, degumming and bleaching. Two American Oil Chemists’ Society (AOCS) standard bleaching earths and two commercial earths were compared for effectiveness in bleaching these dark, yellow-red, crude lesquerella oils. Free fatty acids (1.3%), iodine value (111), peroxide value (<4 meq/kg), unsaponifiables (1.7%) and hydroxyl value (100) were not significantly affected by degumming and bleaching, but phosphorus levels of 8–85 ppm in the crude oils were reduced to 0.5–1.1 ppm in the degummed and bleached oils. Crude oils had Gardner colors of 14, which were reduced to Gardner 9–11 in the degummed and bleached oil, depending on bleach type and quantity used. AOCS colors in the range of 21–25R 68–71Y were obtained. By including charcoal in the bleaching step, a considerably lighter oil could be obtained (Gardner 7).

Abstract: This report examines the use of lipases for isolating fatty acids with Δ5 unsaturation from the seed oil ofLimnanthes alba, or meadowfoam. Seven lipase types and three enzyme configurations (immobilized, “free” and reversemicellar encapsulated) were examined. All lipases discriminated against Δ5 acids to varying degrees, but the degree of discrimination was independent of enzyme configuration. Lipase-catalyzed esterification of meadowfoam oil’s free fatty acids was much more successful for isolating Δ5 acyl groups than was lipolysis. For example, esterification directed byChromobacterium viscosum lipase yielded a free fatty acid product containing >95% of the Δ5 acyl groups at >99% purity.

Abstract: Lesquerella gordonii (Gray) Wats andLimnanthes alba Benth. (Meadowfoam) are species being studied as new and alternative crops. Triglyceride oil from lesquerella contains 55–60% of the uncommon 14-hydroxy-cis-11-eicosenoic acid. Meadowfoam oil has 95% uncommon acids, includingca. 60%cis-5-eicosenoic acid. Both oils are predominantly unsaturated (3% saturated acids), and have similar iodine values (90–91), from which oxirane values of 5.7% are possible for the fully epoxidized oils. Each oil was epoxidized withm-chloro-peroxybenzoic acid, and oxirane values were 5.0% (lesquerella) and 5.2% (meadowfoam). The epoxy acid composition of each product was examined by gas chromatography of the methyl esters, which showed that epoxidizedL. gordonii oil contained 55% 11,12-epoxy-14-hydroxyeicosanoic acid, and epoxidized meadowfoam oil contained 63% 5,6-epoxyeicosanoic acid, as expected for normal complete epoxidation. Mass spectrometry of trimethylsilyloxy derivatives of polyols, prepared from the epoxidized esters, confirmed the identity of the epoxidation products and the straightforward nature of the epoxidation process. Synthesis and characterization of these interesting epoxy oils and derivatives are discussed.

Abstract:Study Objective:SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) under investigation as a treatment for attention-deficit/hyperactivity disorder (ADHD). One concern for any new drug is prolongation of the QT interval, which is associated with increased risk for potentially very harmful ventricular cardiac arrhythmias such as torsades de pointes (TdP). The objective of this study was to assess the effects of SPN-812 at a supratherapeutic dose (1800 mg once daily [QD]) on cardiac repolarization (QTc) in healthy adults.Method:This study was a Phase 1, double-blind (except for the positive control moxifloxacin), randomized, 3-period, 6-sequence crossover design in healthy adult male and female subjects evaluating the electrocardiographic effects of SPN-812. Subjects were randomized to receive a sequence of all 3 treatments – placebo, 400 mg moxifloxacin (positive control), and 1800 mg SPN-812 (supratherapeutic dose). Treatment was given for 2 consecutive days (separated by a washout of at least 4 days). The primary endpoint was based on concentration-QTc effect modeling, evaluating the relationship between plasma concentrations of SPN-812 and its metabolite 5-hydroxyviloxazine glucuronide (5-HVLX-gluc) with the placebo-adjusted change from baseline in QTcI, ΔΔQTcI (QT interval corrected for HR based on the individual-specific QT interval correction method). Secondary endpoints included time point change from baseline in QTcI, QTcF, HR, PR, and QRS; evaluation of the relationship between the plasma concentration of viloxazine and 5-HVLX-gluc and the placebo-adjusted change from baseline in HR, PR, QRS, and QTcF; evaluation of the relationship between the plasma concentration of moxifloxacin and ΔΔQTcI to demonstrate assay sensitivity; and changes in ECG morphology. Safety endpoints included assessment of adverse events and other parameters.Results:The relationship between ΔΔQTcI and viloxazine plasma concentration demonstrated a negative slope (p=0.0012). Predicted mean ΔΔQTcI (2-sided 90% CI) for SPN-812 was -9.7 ms (-11.3, -8.1) at the mean Cmax of 12.4 μg/mL. The relationship of 5-HVLX-gluc and ΔΔQTcI similarly demonstrated a predicted negative slope (p=0.0007) with a predicted mean ΔΔQTcI (2-sided 90% CI) of -9.2 ms (-10.8, -7.8) at the mean Cmax of 10.0 μg/mL. Assay sensitivity was confirmed. Concentration-effect modeling demonstrated no relationship between plasma concentrations of viloxazine and 5-HVLX-gluc and other ECG parameters. The secondary time point analyses demonstrated no effect of SPN-812 on QTcI or other ECG intervals. SPN-812 produced no changes in ECG T wave or U wave morphology.Conclusions:Data from this Phase 1 thorough QT study demonstrate that a supratherapeutic dose of SPN-812, 1800 mg QD, has no effect on cardiac repolarization or other ECG parameters, and is thus not associated with a risk for cardiac arrhythmias such as TdP.Funding Acknowledgements:This research was funded by Supernus Pharmaceuticals, Inc., Rockville, MD.