Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – C-o-group doai
Reexamination Certificate
2002-04-25
2003-07-22
O'Sullivan, Peter (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
C-o-group doai
C514S164000, C568S840000, C568S913000, C568S918000
Reexamination Certificate
active
06596776
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention pertains to a biologically active mixture of high purity, high molecular weight straight chained primary aliphatic alcohols (referred to herein as aliphatic alcohols) having enhanced purity that is isolated from a naturally occurring source such as beeswax. More particularly the invention pertains to a mixture of high purity, high molecular weight straight chained primary aliphatic alcohols that is obtained from saponified and/or unsaponified beeswax by liquid extraction wherein the resulting aliphatic alcohols in the mixture contain 20 to 34 carbon atoms.
2. Description of the State of Art
All kinds of waxes, and more especially beeswax, have always been a matter of interest. This has been the case not only because of their industrial applications, but also because of their chemical composition. The amount of beeswax in honey ranges between 0.9% to 1.13%, depending on the methods used to separate the wax from the honey. This wax contains esters, hydrocarbons, free fatty acids, free alcohols and a long list of minor compounds.
The natural mixture of aliphatic alcohols obtained from beeswax has been studied by several authors to learn about its composition and main features. The obtaining of different mixtures of aliphatic alcohols from various waxes has also been reported. (J. A. Lamberton, et al.,
Australian Journal of Chemistry
, 13:261-268 (1959); A. Horn and J. S. Martic,
Journal of Science Food and Agriculture
, 10:571 (1957); Kreger, (1948); Wimbero, (1904); and Mitsui and Col, (1942)). These studies suggest a method for obtaining aliphatic alcohols based on the homogeneous saponification with alcoholic potassium hydroxide.
Another method reports an extraction of the natural aliphatic alcohol mixture through a high efficiency vacuum. The high vacuum wax distillation for the chemical isolation of mixed derivatives and the extraction of the remaining wax are done using petroleum ether. The solvent is evaporated and the remaining solids are acetylated for further purification through alumina chromatography. Finally, through alkaline hydrolysis, aliphatic alcohols are obtained and then recrystallized in ethanol, showing a melting point range from 62° C. to 82° C.
Blood-lipid lowering effects of a natural mixture of straight chain aliphatic alcohols have been demonstrated by several authors: (F. Liu, et al., “Active Constituents Lowering Blood-Lipid in Beeswax,”
Zhongguo Zhong Yao Zhi
, 21(9):553-4, 576 (1996)); (H. Sho, et al., “Effects of Okinawa Sugar Cane Wax and Fatty Alcohols on Serum and Liver Lipids in the Rats,”
J Nutri Vitaminol
, 30(6):553-559 (1984)); (S. Kato, K. Hamatani, et al., “Octacosanol Effects Lipid Metabolism in Rat Fed on a High Fat Diet,”
Br J Nutr
, 73(3): 433-441 (1995)); and (Kabiry, et al., “Tissue Distribution of Octacosanol in Liver and Muscle of Rats After Serial Administration,”
Ann Nutr Metab
, 39(5):279-284 (1995)); and (I. Gouni-Berthold, et al., “Policosanol: Clinical pharmacology and therapeutic significance of a new lipid-lowering agent,”
Am Heart J
, 143:356-365 (2002)). Many investigational studies based on clinical studies using the natural mixtures of straight chain aliphatic alcohols have been published.
A procedure for obtaining a natural mixture of aliphatic alcohols from animal and vegetable waxes (a natural sourced wax) is also known in the prior art. This prior art procedure is based on the extraction of alcohol mixtures with fluid extractant in the sub- and super-critical states between 20° C. and 100° C. Selective extraction can be carried out with this procedure, but when this is applied to beeswax it is only possible to obtain between 10% to 15% of a C-20 to C-34 alcohol mixture.
Another project (S. Inaa, K. Furukama, T. Masui, K. Honda, J. Ogasawara, and G. Tsubikamoto, “Process for Recovering Primary Normal Aliphatic Higher Alcohols” JP 60-119514 (1996)) proposed a very similar extraction method applied to waxes that is based on fluids (CO
2
with ethylene) in sub- and super-critical states.
There are several different commercial dietary supplements, foods and drugs that aid in the lowering of total blood cholesterol (lowering lipid, LDL-cholesterol, and total cholesterol levels) which are considered as effective, safe and well-tolerated but most produce different adverse side effects. Since lipid-lowering therapy must be chronically administered, safety and tolerability are very important for their definitive acceptance.
It has been described that treatment with some lipid-lowering drugs reduces the tendency for platelet hyperaggregation frequently seen in hyperlipidemic patients and experimental data have shown anti-aggregatory effects mediated by these compounds. Nevertheless, only some cholesterol-lowering drugs show this property.
Atherosclerosis is a variable combination of changes of the intima of the arteries consisting of the focal accumulation of lipids, complex carbohydrates, blood and blood products, fibrous tissue and calcium deposits, frequently also associated with medial changes. Thus, atherosclerosis is known as a multifactorial process and includes hyperlipidemia as a risk factor.
Among the factors contributing to atherosclerosis development, platelet aggregation has a very important place. The granule contents released from platelets activate arachidonic acid, which metabolizes into cyclic endoperoxides. These are mainly transformed into thromboxane A
2
(TXA
2
), a strong vasoconstrictor and platelet aggregatory agent. Platelet aggregation can be elicited by numerous compounds, such as collagen, ADP, and epinephrine. Thus, different experimental “in vivo,” “ex vivo,” or “in vitro” models that test effectiveness of putative antiplatelet drugs commonly test their effect on platelet aggregation induced by these agents. These tests are also used for testing platelet aggregation in healthy volunteers and in patients with diseases which induce hyperaggregability such as hypercholesterolemia and diabetes.
Collagen-induced platelet aggregation is one of the most frequently used tests. Thus, for example, collagen injected intravenously leads to reversible intravascular platelet aggregation “in vivo” and aggregates of platelets enter the vascular microcirculation, subsequently decreasing the count of circulating platelets and simultaneously increasing the plasma malondialdehyde (MDA) concentration. Moreover, in some species the injection of collagen induces mortality produced by thrombosis. In these models, antiplatelet drugs generally prevent the decrease in circulating platelet content and the increase of MDA concentration, as well as collagen induced mortality.
Some drugs showing platelet anti-aggregatory effects are useful for treatment of thrombotic diseases, myocardial infarction, and stroke, but not all show these advantages. On the other hand, there are antithrombotic drugs such as streptokinase and urokinase that mainly act by lytic processes affecting blood coagulation, but not on the platelet aggregation. Since ischemic cardiovascular diseases, stroke and vascular peripheric obstructive pathologies are the main sequence of atherosclerosis, effects of several drugs on these complications are commonly tested. Thus, theoretically a drug showing cholesterol lowering properties that also can prevent these complications by acting on other events involved in these processes must be advantageous for treating these patients. Likewise, reduction of TXA
2
levels has been associated not only with antiplatelet and antithrombotic effects, but also with antischemic effects. The pharmacological screening of antischemic drugs commonly includes the evaluation of their effects on brain-induced global ischemia. Thus, the protective effect of different drugs on rat cerebral ischemia has been determined by this type of evaluation for certain non-steroidal anti-inflammatory drugs (NSAID) which inhibit reactions catalyzed by cyclooxygenase, as well as for specific inhibitors of thromboxane synthetase and prostacyclin (PGI
2
) analogues (M. G.
Bailey David T.
Gamble William R.
Lenoble Rod
Liu Zhengjie
Nichols Rebecca L.
Hauser, Inc.
Hogan & Hartson LLP
O'Rourke Sarah
O'Sullivan Peter
Petersen Steven C.
LandOfFree
High molecular weight primary aliphatic alcohols obtained... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with High molecular weight primary aliphatic alcohols obtained..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and High molecular weight primary aliphatic alcohols obtained... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3045069