Production of linolenic acid from linseed oil

Linolenic acid of more than 95% purity was produced by liquid-liquid extraction of linseed oil fatty acids with wet furfural and hexane in a Podbielniak centrifugal extractor. The minimum ratio of furfural to linseed acids to obtain this purity was 10 to 1. There was no significant change in product purity for solvent ratios between 10 and 15, operating temperatures from 90° to 110°F., and furfural moisture contents between 1.0 and 2.8%. When the solvent ratio is reduced to 8 or the furfural moisture to 0.2%, purity decreases. Oxidation of linseed acids before extraction also results in decreased separation. An estimate based on pilotplant data indicates a “cost to make” (excluding administrative and selling expenses, profit, income taxes, and interest on investment) of 18.0 cents per pound of 97% linolenic acid for a process which includes hydrolyzing linseed oil, separating the fatty acids by liquid-liquid extraction, recovering solvents by distillation, and distilling the fatty acid products. Potential uses for linolenic acid are reviewed.     

Evaluation of the tamper-resistant properties of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets

Context: Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release.

Objective: To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets.

Materials and methods: IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving. Resistance to crushing was tested using manual and powered tools (e.g. spoons, mortar and pestle, blender, coffee grinder). Tampered tablets were tested for suitability for snorting, OC extraction in solvents and ease of drawing into a syringe. Dissolution of IR/ER OC/APAP in gastric fluid with and without ethanol was tested to determine the potential for facilitating precipitous release of opioid from the tablet.

Results: IR/ER OC/APAP tablets were more crush resistant than IR OC/APAP tablets. Heating, freezing and microwaving had no effect on crush resistance of IR/ER OC/APAP tablets. Although a mortar and pestle pulverized IR/ER OC/APAP tablets, upon contact with solvent, the powder formed a thick gel judged unsuitable for absorption through the nasal mucosa and could not be drawn into a syringe. In contrast, powder from crushed IR OC/APAP tablets dissolved readily, was judged suitable for snorting, and was easily drawn into a syringe. Dissolution of IR/ER OC/APAP tablets in gastric fluid was slowed by the addition of ethanol.

Discussion: IR/ER OC/APAP tablets are resistant to crushing and dissolution compared with IR OC/APAP tablets.

Conclusion: IR/ER OC/APAP tablets may have less potential for abuse involving tampering compared with IR OC/APAP tablets.     

Gonadal cell apoptosis: hormone-regulated cell demise

We have studied the release of nerve growth factor (NGF), a protein under consideration for treatment of Alzheimer's Disease, from polymer matrices and microspheres to characterize the stability of NGF, the dynamics of NGF release, and the distribution of NGF within the brain interstitium. Poly(ethylene-co-vinyl acetate) (EVAc) disks and poly(L-lactic acid) (PLA) microspheres were formed by codispersing NGF with one of a variety of molecules. The mass of mouse NGF (mNGF) detected following release from EVAc disks into buffered saline varied five-fold over the range of codispersants studied, with carboxymethyldextran providing optimal release, while the mass of recombinant human NGF (rhNGF) released varied four-fold from both EVAc disks and PLA microspheres, with albumin and carboxymethyldextran providing optimal release. Variation of the codispersant species significantly affected NGF release into buffered saline; it also had a noticeable, but small, effect of the amount of NGF found in the brain tissue following implantation of a polymer device. To improve NGF retention in tissue, NGF was conjugated to 70,000 molecular weight dextran and incorporated into a polymeric device. The distribution of NGF was enhanced by conjugation; comparison of NGF concentrations in the brain to a mathematical model of diffusion and elimination suggested that the elimination rate of NGF-dextran conjugate in the tissue was over seven times slower than the elimination rate of NGF. These results indicate that variation of the properties of the controlled release system may be useful in regulating the time course of NGF delivery to tissue, and that modification of the NGF itself can improve penetration and retention in the brain.     

A phase I/II study of paclitaxel (TAXOL) and concurrent radiotherapy in advanced nonsmall cell lung cancer

OBJECTIVE: Polymerase chain reaction amplification of a portion of the RhC/c/E/e gene could lead to a rapid, accurate determination of fetal RhC/c/E status. The purpose of this study was to evaluate the accuracy of this technique by testing for the first time a large number of deoxyribonucleic acid samples derived from individuals whose RhC/c/E status was established by standard serologic methods. We also evaluated the potential clinical utility of polymerase chain reaction to ascertain fetal antigen status. STUDY DESIGN: Samples were obtained from Centre d'Etude du Polymorphisme Humain families used for studies of genetic variation (n = 655). Deoxyribonucleic acid was extracted by standard techniques. With few modifications, published primers and reaction conditions were used. Samples were digested with restriction enzymes yielding characteristic electrophoresis patterns for RhC/c/E. Clinical utility was assessed by review of all patients evaluated for erythrocyte sensitization. RESULTS: RhC-positive (n = 479), RhC-negative (n = 176), Rhc-positive (n = 524), Rhc-negative (n = 131), RhE-positive (n = 131) and RhE-negative (n = 524) samples were evaluated. The sensitivity of RhC/ c and E typing by polymerase chain reaction was 98.3%, 98.1%, and 96.9%, respectively. The specificity of polymerase chain reaction for identifying the RhC/c/E antigens was 91.5%, 94.7%, and 99.2%, respectively. CONCLUSIONS: Although it would appear that use of polymerase chain reaction to establish RhC/c/E type could aid in evaluation of RhC/c/E sensitization, we are concerned about the instances of antigen-positive individuals characterized as antigen negative. Further study is necessary to determine if this reflects a polymorphism, mutation, a data coding error, or a combination. The Centre d'Etude du Polymorphisme Humain database is known to contain such errors at a rate that may surpass the error rate of our testing. A second molecular technique could be used to achieve better accuracy in the ascertainment of Rh C/c/E type. On the basis of a review of our patient population, molecular deoxyribonucleic acid techniques now available could aid the management of erythrocyte sensitization in pregnancy in > 96% of cases.     

Cyclic fatty acid yields from linseed oil

Increased yields of saturated cyclic fatty acids which are fluid at −50C have been obtained from linseed oil. Depending on reaction conditions, yields varied from 20–42 g of cyclic acids per 100 g of linseed oil. Solvent ratios of 6, 3, and 1.5∶1; catalyst concentrations of 10, 30, 60, and 100%; and reaction temps of 225, 275, 295, and 325C were evaluated. Ethylene glycol and diethylene glycol were compared as reaction solvents. In general, high solvent ratios favored high cyclic acid yields at the lower reaction temperature, but as the temperature increased the effect of solvent ratio decreased. Increasing the percentage excess of sodium hydroxide increased the cyclic acid yield. Diethylene glycol gave higher yields than ethylene glycol at comparable conditions. Presented at the AOCS meeting in Chicago, Ill., October, 1961. A laboratory of the No. Utiliz. Res. & Dev. Div., ARS, U.S.D.A.     

Continuous production of cyclic fatty acids

Kinetic studies of a batch treatment of linseed oil to produce cyclic acids indicated that of a continuous process conducted in a flow-through reactor and involving rapid heat-up of reactants, followed by a short reaction time, might be feasible. Tests were conducted in a continuous system to examine the effects of flow rate (retention time), reaction temp, reaction system pressure and reagents on product yields. The reactant solution (linseed oil-ethylene glycol-sodium hydroxide) was pumped through an externally heated tube and discharged through a back-pressure valve. Maximum cyclic acid yields based on wt of oil were 37% by the continuous method and 40.4% by the batch process when the feed was saturated with nitrogen, and 39.5% and 46.1% for the respective methods when the feed was saturated with ethylene. These differences may be offset by the advantages inherent in a continuous process. Presented in part at the AOCS Meeting, New Orleans, 1962. A laboratory of the No. Utiliz. Res. & Dev. Div., ARS, USDA.     

Cyclic fatty acids from linolenic acid

Linolenic acid of 95% purity was heated with excess alkali in ethylene glycol to produce cyclic fatty acids. Reaction variables, which are associated with the cyclization reaction and which were investigated, included solvent-to-fatty-acid ratio, catalyst concentration, and reaction temperature, headspace gas (N₂ or C₂H₄), and head-space gas pressure. Yields of cyclic acids were improved by increasing solvent ratio (1.5–6 wt basis), reaction temperature (225–295C), and catalyst concentration (10–100% excess). With nitrogen the optimum catalyst concentration was about 100% excess, but when ethylene was used, no increase was obtained beyond 50% excess catalyst. Yields of polymeric acids produced in the reaction generally decreased as cyclic acid yields increased, except in one instance. Higher yields of cyclic fatty acids were obtained with ethylene than with nitrogen under all comparable conditions, and increasing the ethylene pressure to as high as 500 psi improved the yield. Ethylene adds to the conjugated double bonds and is believed to give C₂₀ fatty acids having a 1,4-disubstituted monoene ring in the chain. The maximum yield of monomeric cyclic acids from 95% linolenic acid was 84.6%, the balance being polymeric and unreacted monomeric acids. Monomeric acids from this test contained 95% cyclic acids. Presented at AOCS meeting, New Orleans, 1962. No. Utiliz. Res. & Dev. Div., ARS, U.S.D.A.