ANTIOXIDANT PEPTIDES

Abstract: The present invention provides a method and means for inhibiting lipid oxidation. In accordance with the present invention, a number of novel lipid oxidation suppressant peptides, derived from apolipoprotein A-IV, have been made. These peptides possess lipid oxidation inhibiting properties which when administered orally or intravenously, can be used to decrease atherosclerosis. Since the peptides comprise specific portions of the native apo A-IV protein, there should be no immunogenicity problems associated with their administration to humans.

Description: Antioxidant Peptides This invention was made with government support under Grant No. NEH-DK- 32288 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND OF THE INVENTION The present invention relates generally to a method for treating diseases associated with lipid oxidation. Specifically, the present invention is a new method for treating atherosclerosis and other oxidative disorders. It is generally recognized that high blood cholesterol levels are significant risk factors in cardiovascular disease. Coronary heart disease (CHD) remains the leading cause of death in the industrialized countries. Despite recent declines in CHD mortality, CHD is still responsible for more than 500,000 deaths in the U.S. annually. It is estimated that CHD, directly and indirectly, costs the U.S. more than $100 billion a year. The primary cause of CHD is atherosclerosis, a disease characterized by the deposition of lipids in the arterial vessel wall, resulting in a narrowing of the vessel passages and ultimately hardening the vascular system. Atherosclerosis as manifested in its major clinical complication, ischaemic heart disease, is thought to begin with local injury to the arterial endothelium followed by proliferation of arterial smooth muscle cells from the medial layer to the intimal layer along with deposition of lipid and accumulation of foam cells in the lesion. As the atherosclerotic plaque develops, it progressively occludes more and more blood vessel and can eventually lead to ischaemia or infarction. Therefore, it is desirable to provide a method of inhibiting the progression of atherosclerosis in patients in need thereof. The atherosclerosis is a process of degeneration of the arterial wall and represents the main cause of many vascular pathologies like ischaemic cardiopathies (angina pectoris and myocardial infarction) and cerebral thrombosis, main causes of death in the industrial countries. Many efforts have been carried out to understand the etiology of this pathology of wide diffusion and importance and to find out the possible therapeutic treatments. The atherosclerosis is a process with composite etiology that involves in varied measure different factors and cell types. Ross R. in New Engl. J. Med., 314, 488-495, (1986) assumes that the endothelial damages, caused by exposure to many risk factors, represent the main event in the genesis of the atheroma and in Amer. J. Pathol., 143, 987- 1001, (1993 ) finds out an important cause of the induction of such endothelial damage and of the progress and complication of the atheromatous plaque in the high serum rates of lipids and cholesterol that characterize the hyperlipidaemias and that often aggravate the diabetic pathologies. The pharmacological interventions aimed at lowering the plasma levels of cholesterol and low density lipoproteins (LDL) have proved to be effective in the prevention of the vascular coronary pathologies and in the treatment of atheromatous plaques, as reported by Steinberg D. in J.A.M.A., 253, 2080-2086, (1985) and in Atherosclerosis, 3, 283-301, (1983). The atherogenic risk joined to the LDL appears bound together with not only their plasma concentration but also their qualitative characteristics; the possible modifications of the structure and composition of the LDL in the plasma or in the arterial wall can in fact make these macromolecules more atherogenic, namely more apt to trigger off and to stimulate the formation of the atheromatous plaque, as reported by Steinberg D. in New Engl. J. Med., 320, 915-924, (1989). The oxidative processes that occur by action of oxidizing agents present in the plasma or in the endothelial cells of the arterial wall are of main importance among the modifications that the LDL can undergo in vivo. Many in vitro and in vivo experiments, together with the results of epidemiological investigations, support the hypothesis that this mechanism represent a key event in the development of the atherosclerosis, as reported by Esterbauer H. et al. in Brit. Med. Bull., 49, 566-576, (1993). The endogenous antioxidizers challenge the chain of propagation by means of an effective scavenging of the peroxylic radicals and the concentration of hydroperoxides increases only when the endogenous antioxidizers are depleted (latency period). The reactive species of oxygen that form during the process of oxidation together with monounsaturated aldehydes that stem from the decomposition of the hydroperoxides, mainly malondialdehyde (MDA) and 4-hydroxynonenal, cause important changes in the primary structure of the main LDL apoprotein, the B-100 apolipoprotein (apo B-100). Such modification, by helping the LDL absorption by the macrophages, causes the intracellular accumulation of esters of the cholesterol and the formation of foam cells with subsequent development of the atherosclerotic plaque, as reported by Vanderyse L., et al. in Atherosclerosis, 97, 187-199, (1992). Steinberg D. et al. in Proc. Nat. Acad. Sci. USA, 84, 7725-7729, (1987) show how compounds with antioxidizing action towards the LDL can have a part as anti- atherosclerotic drugs. The effectiveness of a treatment by means of substances having antioxidizing action is based on observations limited to in vitro and animal models and on the in vivo use of the Vitamin E. In fact the atherogenic potentialities of the LDL are remarkably lowered in vitro when the LDL are incubated in presence of antioxidizers, like for instance probucol or Vitamin E, as reported by Esterbaur H. et al. in Amer. J. Clin. Nutr., 53, 314S-321S, (1991). Therefore, on the basis of the above mentioned considerations, it is reasonable to suppose that molecules having both hypolipidemic and antioxidant activity represent a therapeutic development important in the treatment of the disorders of the lipoproteic metabolism and in the prevention of the atherosclerosis. The compounds object of the present invention are endowed with antioxidant and hypoUpidaemic properties, in particular they show the capability to prevent and/or to delay the oxidative modification of the LDL, i.e. they compete with the chain of propagation of the lipidic peroxidation through an effective scavenging of the peroxylic radicals. The oxidative modifications of the low density lipoproteins (LDL) represent, as it has already been seen, a key event in the pathogenesis of the atherosclerosis and therefore the compounds object of the present invention can find useful therapeutical application in the treatment of the atherosclerosis and in the prevention of many vascular pathologies like ischaemic cardiopathies (angina pectoris and myocardial infarction), cerebral thrombosis and peripheral arteriopathies. While the causative factors in the development of atherosclerosis are many, two important ones are elevated serum cholesterol levels and excessive LDL oxidation. SUMMARY OF THE INVENTION The present invention provides a method and means for inhibiting lipid oxidation. In one embodiment, pharmacological composition will comprise an apolipoprotein (apo) A-IV compound, derivative or fragment thereof with a pharmaceutically acceptable carrier, fillers or excipients. The administering step may comprise administering a pharmacological composition comprising an apolipoprotein (apo) A-IV compound, derivative or fragment thereof along with pharmaceutically acceptable carrier, fillers or excipients. The method may be by oral administration of an apolipoprotein (apo) A-IV compound, derivative or fragment thereof or a pharmaceutically acceptable salt or derivative thereof into said mammal. The administering step comprises parenteral administration of the an apolipoprotein (apo) A-IV compound, derivative or fragment thereof or a pharmaceutically acceptable salt or derivative thereof into said mammal. This administration may be by transdermai administration, subcutaneous injection, intravenous injection, intraperitoneal injection, intramuscular injection, intrasternal injection, intrathecal injection, intraventricular and intracerebroventricular injection and infusion techniques. The methods also comprise administering an apolipoprotein (apo) A-IV compound, derivative or fragment thereof or a pharmaceutically acceptable salt or derivative thereof along with a solvent or carrier. The UpophiUc solvent or carrier may be an organic solvent, phosphatidyl choline and cholesterol. Accordingly, an object of the present invention is to provide treating a mammal having a condition associated with Upid oxidation. In addition, a number of novel Upid oxidation suppressant peptides, derived from apolipoprotein A-IV, have been made. These peptides possess lipid oxidation inhibiting properties which when administered oraUy or intravenously, can be used to decrease atherosclerosis. Since the peptides comprise specific portions of the native apo A-IV protein, there should be no immunogenicity problems associated with their administration to humans. The peptides of the present invention correspond to specific areas of the apoUpoprotein A-IV molecule and comprise at least a six amino acid sequence derived from the amino terminal portion of the mature apoUpoprotein A-IV. Larger peptides of 15 and 90 amino acids, each containing within its sequence the aforementioned repeat sequence are also contemplated by the present invention. By "homologues" is meant the conesponding peptides derived from other known apo A-IV proteins and having the same or substantially the same Upid oxidation inhibition properties. By "analogs" is meant substitutions in the amino acid sequences of the peptides, providing the Upid oxidation inhibition properties are retained. Analogs may also encompass additional amino acids, added to the N- and/or C-terminal portion of the peptide. For example, analogs of the peptides of the invention may contain cysteine or another amino acid, at the amino or carboxyl end of the peptide by which the peptide may be covalently attached to a carrier protein, e.g., albumin, for in vivo administration. Other carrier molecules include polyethylene glycol (PEG) which functions to avoid proteolytic cleavage and clearing of peptides from the blood. The peptides of the present invention may be linked to an additional sequence of amino acids by either or both the N-terminus and the C-terminus, wherein the additional sequences are from 1 to about 45 amino acids in length. Such additional amino acid sequences, or linker sequences can be conveniently affixed to a detectable label or solid 5 matrix, or carrier. Labels, solid matrices and carriers that can be used with peptides of the present invention are described below. Typical amino acid residues used for linking are tyrosine, cysteine, lysine, glutamic acid and aspartic acid, or the like. In another embodiment of the invention, the Upid oxidation inhibiting peptides of the present invention substantiaUy correspond to the foUowing amino acid sequences: 0 (A) MFLKAWLTV ALVAΓΓGTQA EVTSDQVANV; (B) MWDYFTQLSN 15 NAKEAVEQLQ KTDVTQQLNT LFQDKLGNΓN TYADDLQNKL VPFAVQLSGH 20 LTKETERVRE EIQKELEDLR AMVI; (C) MLPHANKVSQ; (D) MFGDNVQKLQ EHLRPYATDL QAQINAQTQD; 30 (E) MKRQLTPYIQR; (F) MQTTIQDNVE NLQSS; 35 (G) MVPFANELKE KFNQN; (H) MEGLKGQLTP RANELKATID QNLEDLRSRL APLAEGVQEK LNIHQ; (I) MEGLAFQ; (J) MKKNAEELHT KVSTNΓDQLQ KNLAPLVEDV QSKLKGNTEG LQKSLEDLNK QLDQQVEVFR RAVEPLGDKFN; (K) MALVQQ; (L) MEKFRQQLGS DSGDVESHLS FLEKNLREKV SSF; (M) MSTLQKKGSP DQPLALPLPE QVQEQVQEQV QPKPLES; as weU as homologues and analogs thereof; wherein: A = Ala = Alanine R = Arg = Arginine N = Asn = Asparagine D = Asp = Aspartic acid B = Asx = Asparagine or aspartic acid C = Cys = Cysteine Q = Gin = Glutamine E = Glu Glutamic acid Z = Glx = Glutamine or Glutamic acid G Gly = Glycine H = His = Histidine 1 = He = Isoleucine L = Leu = Leucine κ = Lys = Lysine F = Phe = Phenylalanine P = Pro = Proline s = Ser = Serine τ = Thr = Threonine w = Trp = Tryptophan Y = Tyr = Tyrosine V = Val = Valine The sequences of the peptides listed above under (A), (B), (C), (D), (E), (F), (G), (H), (I), (J), (K), (L), and (M), are set forth as SEQ ID NO: 1-13 respectively. The one-letter symbols used to represent the amino acid residues in the peptides of the present invention are those symbols commonly used in the art. By "substantially conesponding" is meant an amino acid sequence having a homology to any of the Usted sequences of about 70% . The present invention also provides compositions for Upid oxidation inhibition in animals, including man. The compositions have as their active ingredients, at least one of the above peptides according to the present invention, admixed with a physiologically acceptable carrier. The term "pharmaceutically acceptable" refers to a molecular entity or composition that does not produce an aUergic or similar unwanted reaction when administered to animals or humans. The pharmaceuticaUy acceptable carriers used in conjunction with the peptides of the present invention vary according to the mode of administration. For example, the compositions may be formulated in any suitable carrier for oral Uquid formulation such as suspensions, elixirs and solutions. Compositions for Uquid oral dosage include any of the usual pharmaceutical media such as, for example, water, oils, alcohols, flavoring agents, preservatives, coloring agents and the like. In the case of oral solid preparations (powder capsules and tablets) carriers such as starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like may be used. In addition, carriers such as liposomes, microemulsions and self emulsifiable glasses may be used. The compositions of the present invention may also be formulated for intravenous administration. In this instance, the peptides are admixed with sterile water and saUne or other pharmaceuticaUy acceptable carrier. The peptides of the present invention may be altered with modifying structures such as PEG to prevent both proteolysis of the peptides and reduce the clearing of peptides from the blood. Other objects, features and advantages of the present invention wiU become apparent from the foUowing detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of Ulustration only, since various changes and modifications within the scope of the invention wiU become apparent to those skiUed in the art from this detailed description. BRIEF DESCRIPTION OF THE FIGURES Fig. 1 : Inhibition effect of different doses of apoA-IV on copper mediated oxidation of fasting lymph and LDL. Fasting intestinal lymph or LDL were oxidized in the absence or presence of apoA-IV at the concentration indicated. Fasting lymph was oxidized by 100 μM CuSO 4 for 3 h at 37°C( ). LDL (50 μg/ml) was oxidized by 10 μM CuSO for 3 h at 37°C(0). Lipid peroxidation was measured by the formation of TBARS and expressed as the percentage of protection. Results are means ± S.E. of three measurements. * p<0.05 and ** p<0.01 compared to control. Fig. 2: Kinetics of LDL oxidation in the presence or absence of apoUpoproteins. LDL (50 μg/ml) was oxidized using 10 μM CuSO 4 at 30°C in a quartz cuvette. Absorbance readings at 234 nm were taken every 5 min to measure the formation of conjugated dienes. Conjugated diene formation in LDL was determined in the absence of apoUpoproteins (□), or in the presence of 2.5 μg/ml of apoA-IV (O), 5 μg/ml of apoA-IV (•), rat apoE (Δ) or human apoE (A). Fig. 3: Inhibitory effect of apoA-TV during the propagation phase of LDL oxidation. LDL oxidation, monitored by the conjugated diene assay, was allowed to proceed to the propagation phase of oxidation. ApoA-IV was added to the oxidation reaction during the propagation phase, and conjugated dienes were continuously measured in samples containing only LDL (D), LDL plus tris-saline (X ), LDL plus 5 μg/ml apoA- IV (Δ), LDL plus 10 μg/ml apoA-IV (O), and LDL plus 20 μg/ml apoA-IV (•). The inset shows the change in slope before and after the addition of apoA-IV. DETAILED DESCRIPTION OF THE INVENTION The present invention provides for a number of lipid oxidation inhibiting peptides of approximately 5-90 amino acids in length, which substantially coπespond in sequence to amino acid sequence found in specific portions of apolipoprotein A-IV ("apo A-IV")- Atherosclerosis is a disease state characterized by the development and growth of atherosclerotic lesions or plaque. The identification of those patients who are in need of treatment for atherosclerosis is weU within the abiUty and knowledge of one of ordinary skttl in the art. For example, individuals who are either suffering from cUnicaUy significant atherosclerosis or who are at risk of developing clinically significant atherosclerosis are patients in need of treatment for atherosclerosis. A cUnician ofordinary skiU in the art can readily determine, by the use of clinical tests, physical examination and medical/family history, if an individual is a patient in need of treatment for atherosclerosis. An effective anti-atherosclerotic amount is an amount which is effective in inhibiting the development or growth of atherosclerosis in a patient in need thereof. As such, successful treatment of a patient for atherosclerosis is understood to include effectively slowing, interrupting, arresting, or stopping atherosclerotic lesion or plaque development or growth and does not necessarily indicate a total eUrnination of atherosclerosis. It is further understood and appreciated by those of ordinary skiU in the art that successful treatment for atherosclerosis can include prophylaxis in preventing atherosclerotic lesion or plaque formation. Peroxidation of LDL lipid, such as the unsaturated fatty acid portions of LDL cholesteryl esters and phosphoUpids, is known to faciUtate the deposition of cholesterol in macrophages which subsequently are deposited in the vessel waU and are transformed into foam ceUs. The identification of those patients who are in need of inhibition of peroxidation of LDL lipid is well within the ability and knowledge of one of ordinary skill in the art. For example, those individuals who are in need of treatment for atherosclerosis as defined hereinabove, are also patients who are in need of inhibition of peroxidation of LDL lipid. An effective antioxidant amount is an amount which is effective in inhibiting the peroxidation of LDL lipid in a patient's blood. As used herein, the term "patient" refers to a warm-blooded animal or mammal which is in need of treatment for a chronic heart disease, atherosclerosis, hypercholesterolemia or which is in need of inhibiting oxidation. A "therapeuticaUy effective amount" is an amount which is effective, upon single or multiple dose administration to the patient, in providing reUef of symptoms associated with atherosclerotic diseases. As used herein, "reUef of symptoms" refers to decrease in severity over that expected in the absence of treatment and does not necessarily indicate a total elimination or cure of the disease. ReUef of symptoms is also intended to include prophylaxis. As used herein, "peptide" refers to a linear series of less than about 100 amino acid residues connected to one another by peptide bonds between the alpha-amino and carboxy groups of adjacent amino acid residues. The term "synthetic peptide" is intended to refer to a chemicaUy derived chain of amino acid residues linked together by peptide bonds and which is free of naturaUy occurring proteins and fragments thereof. AdditionaUy, analogs, homologues, fragments, chemical derivatives and pharmaceuticaUy acceptable salts of the novel peptides provided herein are included within the scope of the term "peptide". By "peptide analog" is meant a peptide which differs in amino acid sequence from the native peptide only by conservative amino acid substitutions, for example, substitution of Leu for Val, or Arg for Lys, etc., or by one or more non-conservative amino acid substitutions, deletions, or insertions located at positions which do not destroy the biological activity of the peptide (in this case, the ability of the peptide to target vascular lesions). A peptide analog, as used herein, may also include, as part or aU of its sequence, one or more amino acid analogues, molecules which mimic the structure of amino acids, and/or natural amino acids found in molecules other than peptide or peptide analogues. By "homologues" is meant the corresponding peptides derived from other known apo A-IV proteins having the same or substantiaUy the same appetite suppressant and feeding inhibition properties. By "analogs" is meant substitutions or alterations in the amino acid sequences of the peptides of the invention, which substitutions or alterations do not aboUsh the appetite suppressant or feeding inhibition properties of the peptides. Thus, an analog might comprise a peptide having a substantiaUy identical amino acid sequence to a peptide provided herein as SEQ ID NO: 1-13 and in which one or more amino acid residues have been conservatively substituted with chemicaUy similar amino acids. Examples of conservative substitutions include the substitution of a non-polar (hydrophobic) residue such as isoleucine, valine, leucine or methionine for another. Likewise, the present invention contemplates the substitution of one polar (hydrophiUc) residue such as between arginine and lysine, between glutamine and asparagine, and between glycine and serine. Additionally, the substitution of a basic residue such as lysine, arginine or histidine for another or the substitution of one acidic residue such as aspartic acid or glutamic acid for another is also contemplated. The phrase "conservative substitution" also includes the used of chemically derivatized residues in place of a non-derivatized residues as long as the peptide retains the requisite appetite suppressant or feeding inhibition properties. Analogs also include the presence of additional amino acids or the deletion of one or more amino acids which do not affect biological activity. For example, analogs of the subject peptides may contain an N- or C-teπninal cysteine, by which, if desired, the peptide may be covalently attached to a carrier protein, e.g., albumin. Such attachment, it is beUeved, wiU minimize clearing of the peptide from the blood and also prevent proteolysis of the peptides. ) The practice of the present invention employs, unless otherwise indicated, conventional techniques of synthetic organic chemistry, protein chemistry, molecular biology, microbiology, and recombinant DNA technology, which are weU within the skiU of the art. Such techniques are explained fully in the Uterature. In preferred embodiments, the peptide or peptide analog is water soluble; or is soluble in a physiological fluid, preferably, one which is at physiological pH, for example, blood plasma. In another prefened embodiment, the peptide has a molecular conformation analogous to the molecular conformation (size, shape, charge) of a surface region of the apoUpoprotein A-IV (apo A-IV) moiety. Examples of prefened peptide or peptide analogues include: Met-Phe-I^u-Lys-Ala-V -Val-Leu-Thr-Val-Ala-Leu-Val-Ala-Ile-Thr-Gly-Thr-Gln- Ala-Glu-Val-Thr-Ser-Asp-Gln-Val-Ala-Asn-Val (SEQ LD NO:l); Met-Trp-Asp-Tyr-Phe-Thr-Gln-Leu-Ser-Asn-Asn-Ala-Lys-Glu-Ala-Val-Glu-Gln-Leu- Gm-Lys-Thr-Asp-V -Thr-Gln-Gln-Leu-Asn-Thr-Leu-Phe-Gln-Asp-Lys-Leu-Gly-Asn-Ile- Asn-Thr-Tyr-Ala-Asp-Asp-Leu-Gln-Asn-Lys-Leu-Val-Pro-Phe-Ala-Val-Gln-Leu-Ser- Gly-His-Leu-Thr-Lys-Glu-Thr-Glu-Arg-Val-Arg-Glu-Glu-Ile-Gln-Lys-Glu-Leu-Glu-Asp- Leu-Arg-Ala-Met- Val-Ile (SEQ ID NO:2); Met-Leu-Pro-His-Ala-Asn-Lys-Val-Ser-Gln (SEQ ID NO:3); Met-Phe-Gly-Asp-Asn-Val-Gln-Lys-Leu-Gln-Glu-His-Leu-Arg-Pro-Tyr-Ala-Thr-Asp- Leu-Ghi-Ala-Gm-Ile-Asn-Ala-Gln-Thr-Gln-Asp (SEQ ID NO:4); Met-Lys-Arg-Gln-Leu-Thr-Pro-Tyr-De-Gln-Arg (SEQ ID NO: 5); Met-Gm-Thr-Thr-Ile-Gln-Asp-Asn-Val-Glu-Asn-Leu-Gm-Ser-Ser (SEQ ID NO:6); Met-Val-Pro-Phe-Ala-Asn-Glu-Leu-Lys-Glu-Lys-Phe-Asn-Gln-Asn (SEQ ID NO:7); Met-Glu-Gly-Leu-Lys-Gly-Gln-Leu-Thr-Pro-Arg-Ala-Asn-Glu-Leu-Lys-Ala-Thr-Ile- Asp-Gln-Asn-Leu-Glu- Asp-Leu- Arg-Ser-Arg-Leu-Ala-Pro-Leu-Ala-Glu-Gly-Val-Gln- Glu-Lys-Leu-Asn-Ile-His-Gln (SEQ ID NO: 8); Met-Glu-Gly-Leu-Ala-Phe-Gln (SEQ ID NO:9); Met-Lys-Lys-Asn-Ala-Glu-Glu-Leu-His-Thr-Lys-Val-Ser-Thr-Asn-Ile-Asp-Gln-Leu- Gln-Lys-Asn-Leu-Ala-Pro-Leu-Val-Glu-Asp-Val-Gln-Ser-Lys-Leu-Lys-Gly-Asn-Thr- Glu-Gly-Leu-Gln-Lys-Ser-Leu-Glu-Asp-Leu-Asn-Lys-Gln-Leu-Asp-Gln-Gln-Val-Glu- Val-Phe-Arg-Arg-Ala-Val-Glu-Pro-Leu-Gly-Asp-Lys-Phe-Asn (SEQ ID NO: 10); Met- Ala-Leu- Val-Gln-Gln (SEQ ID NO: 11); Met-Glu-Lys-Phe-Arg-Gln-Gln-Leu-Gly-Ser-Asp-Ser-Gly-Asp-Val-Glu-Ser-His-Leu- Ser-Phe-Leu-Glu-Lys-Asn-Leu-Arg-Glu-Lys-Val-Ser-Ser-Phe (SEQ ID NO: 12); Met-Ser-Thr-Leu-Gln-Lys-Lys-Gly-Ser-Pro-Asp-Gln-Pro-Leu-Ala-Leu-Pro-Leu-Pro- Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Pro-Lys-Pro-Leu-Glu-Ser (SEQ ID NO: 13); and derivatives, analogues, homologues, fragments and mixtures thereof. In various other prefened embodiments, the peptide or peptide analog has an acetylated amino terminus and/or an amidated carboxy terminus. Examples of such peptide or peptide analogues include: H2N-Met-Phe-Leu-Lys-Ala-Val-Val-Leu-Thr-Val-Ala-Leu-Val-Ala-Ile-Thr-Gly-Thr- Gin- Ala-Glu-Val-Thr-Ser- Asp-Gin- Val- Ala- Asn-Val-CONH2 (SEQ ID NO: l); CH3CONH-Met-Phe-Leu-Lys-Ala-Val-Val-Leu-Thr-Val-Ala-Leu-Val-Ala-Ile-Thr-Gly- Thr-Gln-Ala-Glu-Val-Thr-Ser- Asp-Gin- Val- Ala- Asn-Val-CONH2 (SEQ LD NO:l); H2N-Met-Trp-Asp-Tyr-Phe-Thr-Gln-Leu-Ser-Asn-Asn-Ala-Lys-Glu-Ala-Val-Glu-Gln- Leu-Gln-Lys-Thr-Asp-Val-Thr-Gln-Gln-Leu-Asn-Thr-Leu-Phe-Gln-Asp-Lys-Leu-Gly- Asn-Ile-Asn-Thr-Tyr-Ala-Asp-Asp-Leu-Gln-Asn-Lys-Leu-Val-Pro-Phe-Ala-Val-Gln-Leu- Ser-Gly-His-Leu-Thr-Lys-Glu-Thr-Glu-Arg-Val-Arg-Glu-Glu-Ile-Gln-Lys-Glu-Leu-Glu- Asp-Leu-Arg-Ala-Met-Val-Ile-CONH2 (SEQ ID NO:2); CH3CO ^-Met-Trp-Asp-Tyr-Phe-T ^-Gln-Leu-Ser-Asn-Asn-Ala-Lys-Glu-Ala-Val- Glu-Gm-lΛU-Gh-Lys-Trij-Asp-V -Thr-Gm-Gln-Leu-Asn-Thr-Leu-Phe-Gln-Asp-Lys- IL^u-Gly-A-sn-De-Asn-Thr-Tyr-Ala-Asp-Asp-Leu-Gln-Asn-Lys-Leu-Val-Pro-Phe-Ala-Val- Gta-Leu-Ser-Gly-His-Leu-Tlir-Lys-Glu-Thr-Glu-Arg-Val-Arg-Glu-Glu-Ile-Gln-Lys-Glu- Leu-Glu-Asp-Leu-Arg-Ala-Met-Val-De-CONH2 (SEQ ID NO:2); H2N-Met-Leu-Pro-His-Ala-Asn-Lys-Val-Ser-Gln-CONH2 (SEQ ID NO:3); CH3CONH-Met-Leu-Pro-His-Ala-Asn-Lys-Val-Ser-Gln-CONH2 (SEQ ID NO:3); H2N-Met-Phe-Gly-Asp-Asn-Val-Gln-Lys-Leu-Gln-Glu-His-Leu-Arg-Pro-Tyr-Ala-Thr- Asp-Leu-Gln-Ala-Gln-Ile-Asn-Ala-Gln-Thr-Gln-Asp-CONH2 (SEQ ID NO:4); CH3CONH-Met-Phe-Gly-Asp-Asn-Val-Gln-Lys-Leu-Gln-Glu-His-Leu-Arg-Pro-Tyr- Ala-Thr-Asp-Leu-Gln-Ala-GUι-Ile-Asn-Ala-Gln-Thr-Gln-Asp-CONH2 (SEQ ID NO:4); H2N-Met-Lys-Arg-Gln-Leu-Thr-Pro-Tyr-Ile-Gln-Arg-CONH2 (SEQ ED NO: 5); CH3CONH-Met-Lys-Arg-Gln-Leu-Thr-Pro-Tyr-Ile-Gln-Arg-CONH2 (SEQ ID NO:5); H2N-Met-Gln-Thr-Thr-πe-Gln-Asp-Asn-Val-Glu-Asn-Leu-Gln-Ser-Ser-CONH2 (SEQ ID NO:6); CH3CONH-Met-Gln-Thr-Thr-Ile-Gln-Asp-Asn-Val-Glu-Asn-Leu-Gln-Ser-Ser-CONH2 (SEQ ID NO:6); H2N-Met-Val-Pro-Phe-Ala-Asn-Glu-Leu-Lys-Glu-Lys-Phe-Asn-Gln-Asn-CONH2 (SEQ ID NO:7); CH3CONH-Met-Val-Pro-Phe-Ala-Asn-Glu-Leu-Lys-Glu-Lys-Phe-Asn-Gln-Asn- CONH2 (SEQ ID NO: 7); H2N-Met-Glu-Gly-Leu-Lys-Gly-Gln-Leu-Thr-Pro-Arg-Ala-Asn-Glu-Leu-Lys-Ala-Thr- πe-Asp-Gln-Asn-Leu-Glu-Asp-Leu-Arg-Ser-Arg-Leu-Ala-Pro-Leu-Ala-Glu-Gly-Val-Gm- Glu-Lys-Leu-Asn-Ile-His-Gln-CONH2 (SEQ ID NO: 8); CH3CONH-Met-Glu-Gly-Leu-Lys-Gly-Gln-Leu-Thr-Pro-Arg-Ala-Asn-Glu-Leu-Lys- Ala-Thr-Ile-Asp-Gln-Asn-Leu-Glu-Asp-Leu-Arg-Ser-Arg-Leu-Ala-Pro-Leu-Ala-Glu-Gly- Val-Gln-Glu-Lys-Leu-Asn-Ile-His-Gln-CONH2 (SEQ ID NO: 8); H2N-Met-Glu-Gly-Leu-Ala-Phe-Gln-CONH2 (SEQ ID NO: 9); CH3CONH-Met-Glu-Gly-Leu-Ala-Phe-Gln-CONH2 (SEQ ID NO:9); H2N-Met-Lys-Lys-Asn-Ala-Glu-Glu-Leu-His-Thr-Lys-Val-Ser-Thr-Asn-Ile-Asp-Gln- Leu-Gln-Lys-Asn-Leu-Ala-Pro-Leu-Val-Glu-Asp-Val-Ghi-Ser-Lys-Leu-Lys-Gly-Asn- Thr-Glu-Gly-Leu-Gln-Lys-Ser-Leu-Glu-Asp-Leu-Asn-Lys-GUi-Leu-Asp-Gln-GUi-Val- Glu-Val-Phe-Arg-Arg-Ala-Val-Glu-Pro-Leu-Gly-Asp-Lys-Phe-Asn-CONH2 (SEQ ID NO: 10); CH3CONH-Met-Lys-Lys-Asn-Ala-Glu-Glu-Leu-His-Thr-Lys-Val-Ser-Thr-Asn-Ile- Asp-Ghi-Leu-Gui-Lys-Asn-Leu-Ala-Pro-Leu-Val-Glu-Asp-Val-Gm-Ser-Lys-Leu-Lys- Gly-Asn-Thr-Glu-Gly-Leu-GUi-Lys-Ser-Leu-Glu-Asp-Leu-Asn-Lys-GUi-Leu-Asp-Gln- Gln-Val-Glu-Val-Phe-Arg-Arg-Ala-Val-Glu-Pro-Leu-Gly-Asp-Lys-Phe-Asn-CONH2 (SEQ ID NO: 10); H2N-Met- Ala-Leu- Val-Gln-Gln-CONH2 (SEQ ID NO: 11); CH3CONH-Met- Ala-Leu- Val-Gln-Gln-CONH2 (SEQ ED NO: 11); H2N-Met-Glu-Lys-Phe-Arg-Gln-Gln-Leu-Gly-Ser-Asρ-Ser-Gly-Asρ-Val-Glu-Ser-His- Leu-Ser-Phe-Leu-Glu-Lys-Asn-Leu-Arg-Glu-Lys-Val-Ser-Ser-Phe-CONH2 (SEQ ID NO: 12); CH3CONH-Met-Glu-Lys-Phe-Arg-Gln-Gln-Leu-Gly-Ser-Asp-Ser-Gly-Asp-Val-Glu- Ser-His-Leu-Ser-Phe-Leu-Glu-Lys-Asn-Leu-Arg-Glu-Lys-Val-Ser-Ser-Phe-CONH2 (SEQ ID NO: 12); H2N-Met-Ser-Thr-Leu-Gln-Lys-Lys-Gly-Ser-Pro-Asp-GUι-Pro-Leu-Ala-Leu-Pro-Leu- Pro-Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Glu-Gln-Val-GUi-Pro-Lys-Pro-Leu-Glu-Ser- CONH2 (SEQ ID NO: 13); CH3 CONH-Met-Ser-Thr-Leu-Gln-Lys-Lys-Gly-Ser-Pro-Asp-Gln-Pro-Leu-Ala-Leu- Pro-Leu-Pro-Glu-Gto-Val-Gm-Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Pro-Lys-Pro-Leu-Giu- Ser-CONH2 (SEQ ID NO: 13); and derivatives, analogues, homologues, fragments and mixtures thereof. By "derived from" is meant having an amino acid sequence identical or substantiaUy identical to the sequence of, as used herein, a vascular-associated protein. By "substantiaUy identical to" is meant having an amino acid sequence which differs only by conservative amino acid substitutions or by non-conservative amino acid substitutions, deletions, or insertions located at positions which do not destroy the biological activity of the peptide. It is possible to design any number of peptide analogues, having different amino acid sequences, provided that the local charge distribution (and overall net charge) and secondary structure, and hence the biological activity is maintained. Such peptide analogues wiU generaUy differ from the native protein sequences by conservative amino acid substitutions (e.g., substitution of Leu for VaL or Arg for Lys, etc.) weU known to those skilled in the art of biochemistry. The peptides, once designed, can be synthesized by any of a number of estabUshed procedures, including, e.g., the expression of a recombinant DNA encoding that peptide in an appropriate host ceU. Alternatively, these peptides can be produced by the estabUshed procedure of soUd phase peptide synthesis. Briefly, this procedure entails the sequential assembly of the appropriate amino acids into a peptide of a desired sequence whUe the end of the growing peptide is linked to an insoluble support. UsuaUy, the carboxyl terminus of the peptide is linked to a polymer from which it can be Uberated upon treatment with a cleavage reagent. The peptides so synthesized are then labeUed with a reagent which enables the monitoring of the peptide after its administration to a patient. As used herein, the term "substantially corresponds" means a peptide amino acid sequence having approximately 70% homology in amino acid sequence to an apolipoprotein A-IV peptide. The term "chemical derivative" is meant to include any peptide derived from a peptide of the present invention and in which one or more amino acids have been chemicaUy derivatized by reaction of one or more functional side groups of the amino acid residues present in the peptide. Thus, a "chemical derivative" as used herein is a peptide which is derived from the peptides identified herein by one or more chemical steps. Examples of derivatized molecules include molecules where free amino groups have been derivatized to form amine hydrochlorides, p-toluene sulfonyl groups, carbobenzoxy groups, t-butyloxycarbonyl groups, thiourethane-type derivatives, trifluroroacetyl groups, chioroacetyl groups or formyl groups. Free carboxyl groups may be derivatized to form salts, methyl and ethyl esters or other types of esters or hydrazides. Free hydroxyl groups may be derivatized to form 0-acyl or 0-alkyl derivatives. The imidazole nitrogen of histidine may be derivatized to form N-im-benzyUiistidine. Also included as chemical derivatives are those peptides which contain one or more naturaUy occurring amino acid derivatives of the twenty standard amino acids. For example, 4- hydroxyproline may be substituted for proline; 5-hydroxylysine may be substituted for lysine; 3-methylhistidine may be substituted for histidine; homoserine may be substituted for serine; and oirύthine may be substituted for lysine. The term "fragment" refers to any subject peptide having an amino acid sequence shorter than that of any peptide depicted in SEQ ID NO: 1-13 and which a fragment retains the appetite suppressant or feeding inhibition properties as the subject peptides. The peptides of the present invention, homologues and analogs thereof may be synthesized by a number of known techniques. For example, the peptides may be prepared using the soUd-phase synthetic technique or other peptide synthesis techniques weU known to those skiUed in the art. The peptides of the present invention might also be prepared by chemical or enzymatic cleavage from larger portions of the apolipoprotein A-IV molecule or from the entire apo A-IV molecule. Additionally, the peptides of the present invention may also be prepared by recombinant DNA techniques. For most of the amino acids used to build proteins, more than one coding nucleotide triplet (codon) can code for a particular amino acid residue. This property of the genetic code is known as redundancy. Therefore, a number of different nucleotide sequences may code for a particular subject eating suppressant peptide. The present invention also contemplates a deoxyribonucleic acid (DNA) molecule or segment that defines a gene coding for, i.e., capable of expressing, a subject polypeptide or a subject chimeric polypeptide from which a polypeptide of the present invention may be enzymaticaUy or chemicaUy cleaved. DNA molecules that encode the subject peptides can be synthesized by chemical techniques, for example, the phosphotriester method of Matteuccie et al, Chem. Soc. 103:3185 (1981). Using a chemical DNA synthesis technique, desired modifications in the peptide sequence can be made by making substitutions for bases which code for the native amino acid sequence. Ribonucleic acid equivalents of the above described DNA molecules may also be used. A nucleic acid molecule comprising a vector capable of repUcation and expression of a DNA molecule defining coding sequence for a subject polypeptide or subject chimeric polypeptide is also contemplated. The peptides of the present invention are preferably chemically synthesized by the Merrifield soUd phase technique. In general, the method comprises the sequential addition of one or more amino acid residues to a growing peptide chain. Normally, either the amino or carboxyl group of the first amino acid residue is protected by a suitable, selectively removable protecting group. A different, selectively removable protecting group is utilized for amino acids containing a reactive side group such as lysine. Any peptide of the present invention may be used in the form of a pharmaceutically acceptable salt. Suitable acids which are capable of forming salts with the peptides of the present invention include inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfuric acid, phosphoric acid and the like; and organic acids such as formic acid, acetic acid, propionic acid, glycoUc acid, lactic acid, pyruvic acid, oxaUc acid, malonic acid, succinic acid, maleic acid, fumaric acid, anthraniUc acid, cinnamic acid, naphthalene sulfonic acid, sulfaniUc acid or the like. Suitable bases capable of forming salts with the subject peptides include inorganic bases such as sodium hydroxide, ammonium hydroxide, potassium hydroxide and the like; and organic bases such as mono-, di-and tri-alkyl amines (e.g., triethyl amine, dusopropyl amine, methyl amine, dimethyl amine and the like) and optionaUy substituted ethanolamines (e.g. ethanolamine, diethanolamine and the like). The peptides of the present invention were synthesized using an automatic soUd phase peptide synthesizer (MiUigen 9050). The synthesis was started by packing a column with a mixture of polystyrene resin (that has attached to it the C terminus amino acid of the target peptide) and glass beads (150-220 micron diameter). The amino acid bound to the resin was protected prior to packing the column and the process of peptide synthesis started by first washing the column with a 20% v/v solution of piperidine / N,N-dimethyl formamide (DMF) in order to deprotect the C teirninus residue. The next residue, an FMOC protected L-amino acid (in the form of a pentafluorophenyl ester) was dissolved in a solution of hydroxybenzotriazole (HOBT/DMF) and delivered to the instrument column. In order to ensure complete coupling, the solution of amino acid/DMF was passed over the column for an extended period of 45-90 minutes. If residue attachment proved difficult due to stearic reasons, the coupling time was extended by a manual modification of the instrument's buUt in chemical protocols. The protocol for synthesis basicaUy consisted of a number of cycles, each one performing the following operations: deprotection of previous residue with piperidine, washing of the column with DMF, and attachment of the next residue. In determining the therapeuticaUy effective amount or dose, the effective antioxidant amount or dose of an apoUpoprotein (apo) A-IV compound, derivative or fragment thereof, a number of factors are considered by the attending diagnostician, including, but not limited to: the species of the mammal; its size, age, and general health; the response of the individual patient; the particular compound administered; the mode of administration; the bioavaUabiUty characteristics of the preparation administered; the dose regimen selected; the use of concomitant medication; and other relevant circumstances. A therapeuticaUy effective amount wiU generaUy vary from about 1 miUigram per kUogram of body weight per day (mg/kg/day) to about 5 grams per kilogram of body weight per day (gm/kg/day). A daily dose of from about 1 mg/kg to about 500 mg/kg is preferred. However, it is understood that the present invention is not limited by any particular theory or proposed mechanism to explain its effectiveness in an end-use appUcation. In effecting treatment of a patient, an apoUpoprotein (apo) A-IV compound, derivative, analog, homolog, fragment and mixtures thereof can be administered in any form or mode which makes the compound bioavaUable in effective amounts, including oral and parenteral routes. For example, the compound can be administered orally, subcutaneously, intramuscularly, intravenously, transdermally, intranasally, rectaUy, and the like. Oral administration is generally preferred. One skilled in the art of preparing formulations can readily select the proper form and mode of administration depending upon the relevant circumstances. An apoUpoprotein (apo) A-IV compound, derivative, analog, homolog, fragment and mixtures thereof can be administered in the form of pharmaceutical compositions or medicaments which are made by combining an apoUpoprotein (apo) A-IV compound, derivative, analog, homolog, fragment and mixtures thereof with pharmaceuticaUy acceptable carriers or excipients, the proportion and nature of which are determined by the chosen route of administration, and standard pharmaceutical practice. The pharmaceutical compositions or medicaments are prepared in a manner weU known in the pharmaceutical art. The carrier or excipient may be a soUd, semi-soUd, or Uquid material which can serve as a vehicle or medium for the active ingredient. Suitable carriers or excipients are weU known in the art. The pharmaceutical composition may be adapted for oral or parenteral use and may be administered to the patient in the form of tablets, capsules, suppositories, solution, suspensions, or the like. The pharmaceutical compositions may be administered oraUy, for example, with an inert dUuent or with an edible carrier. They may be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, an apoUpoprotein (apo) A-IV compound, derivative or fragment thereof may be incorporated with excipients and used in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, chewing gums and the Uke. These preparations should contain at least 4% of an apolipoprotein (apo) A-IV compound, derivative or fragment thereof the active ingredient, but may be varied depending upon the particular form and may conveniently be between 4% to about 70% of the weight of the unit. The amount of the active ingredient present in compositions is such that a unit dosage form suitable for administration will be obtained. The tablets, piUs, capsules, troches and the Uke may also contain one or more-of the foUowing adjuvants: binders, such as microcrystaUine ceUulose, gum tragacanth or gelatin; excipients, such as starch or lactose, disintegrating agents such as alginic acid, Primogel, corn starch and the Uke; lubricants, such as magnesium stearate or Sterotex; gUdants, such as coUoidal siUcon dioxide; and sweetening agents, such as sucrose or saccharin may be added or flavoring agents, such as peppermint, methyl saUcylate or orange flavoring. When the dosage unit form is a capsule, it may contain, in addition to materials of the above type, a Uquid carrier such as polyethylene glycol or a fatty oU. Other dosage unit forms may contain other various materials which modify the physical form of the dosage unit, for example, as coatings. Thus, tablets or piUs may be coated with sugar, sheUac, or other enteric coating agents. A syrup may contain, in addition to the active ingredient, sucrose as a sweetening agent and certain preservatives, dyes and colorings and flavors. Materials used in preparing these various compositions should be pharmaceuticaUy pure and non-toxic in the amounts used. For the purpose of parenteral administration, an apoUpoprotein (apo) A-IV compound, derivative, analog, homolog, fragment or mixtures thereof may be incorporated into a solution or suspension. These preparations should contain at least 0.1% of a compound of the invention, but may be varied to be between 0.1 and about 50% of the weight thereof. The amount of the active ingredient present in such compositions is such that a suitable dosage will be obtained. When administered intravenously, the peptide compositions may be combined with other ingredients, such as carriers and/or adjuvants. The peptide can also be covalently attached to a protein carrier, such as albumin, so as to minimize clearing of the peptides. There are no limitations on the nature of the other ingredients, except that they must be pharmaceuticaUy acceptable, efficacious for their intended administration and cannot degrade the activity of the active ingredients of the compositions. The peptide compositions of the invention may also be impregnated into transdermai patches or contained in subcutaneousi inserts, preferably in a Uquid or semi-Uquid form A which patch or insert time releases therapeuticaUy effective amounts of one or more of the subject peptides. The pharmaceutical forms suitable for injection include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In aU cases the ultimate solution form must be sterile and fluid. Typical carriers include a solvent or dispersion medium containing, for example, water buffered aqueous solutions (i.e., biocompatible buffers), ethanol, polyols such as glycerol, propylene glycol, polyethylene glycol, suitable mixtures thereof, surfactants or vegetable oUs. Sterilization can be accompUshed by any art-recognized technique, including but not limited to, filtration or addition of antibacterial or antifungal agents, for example, paraben, chlorobutanol, phenol, sorbic acid or thimerosal. Further, isotonic agents such as sugars or sodium chloride may be incorporated in the subject compositions. Production of sterile injectable solutions containing the subject peptides is accomplished by incorporating these compounds in the required amount in the appropriate solvent with various ingredients enumerated above, as required, followed by sterilization, preferably filter sterilization. To obtain a sterile powder, the above solutions are vacuum- dried or freeze-dried as necessary. The solutions or suspensions may also include one or more of the foUowing adjuvants depending on the solubiUty and other properties of an apoUpoprotein (apo) A- r compound, derivative or fragment thereof: sterile dUuents such as water for injection, saline solution, fixed oUs, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl paraben; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylene diaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of toxicity such as sodium chloride or dextrose. The parenteral preparation can be enclosed in ampules, disposable syringes or multiple dose vials made of glass or plastic. The pharmacological composition wiU preferably comprise an apoUpoprotein (apo) A-IV or derivative or fragment thereof along with a pharmaceuticaUy acceptable carrier, fiUers or excipients. The administering step may comprise administering a pharmacological composition comprising an apoUpoprotein (apo) A-IV compound, derivative or fragment thereof along with pharmaceuticaUy acceptable carrier, fillers or excipients. The methods may be by oral aciministration of the antioxidant composition or a pharmaceutically acceptable salt or derivative thereof into said mammal. The methods according to the present invention preferable allows the administration of the antioxidant molecule is administered in a unitary dose of from about 1 to about 1000 mg. A unitary dose is generally administered from about 1 to about 3 time a day. The administering step may comprise parenteral administration of the antioxidant compound or a pharmaceutically acceptable salt or derivative thereof into said mammal. This administration may be by transdermai administration, subcutaneous injection, intravenous injection, intraperitoneal injection, intramuscular injection, intrasternal injection, intrathecal injection, intracerebroventricular injection and infusion techniques. The method of also comprises adininistering antioxidant compound or a pharmaceuticaUy acceptable salt or derivative thereof along with a UpophiUc compound, such as a UpophiUc solvent or carrier. The UpophiUc solvent or carrier may be an organic solvent, phosphatidyl choline and cholesterol. The pharmaceutical compositions of the present invention can be formulated for the oral, subUngual, subcutaneous, intravenous, transdermic or rectal administrations in dosage units and in admixture with pharmaceutical excipients or vehicles. Convenient dosage forms include, among those for oral administration, tablets, powders, granulates, and, among those for parenteral administration, solutions especiaUy for transdermai administration, subcutaneous injection, intravenous injection, intraperitoneal injection, intramuscular injection, intrasternal injection, intrathecal injection and infusion techniques. The dosage can vary widely as a function of the age, weight and state of health of the patient, the nature and the severity of the aUment, as well as of the administration route. These doses can naturally be adjusted for each patient according to the results observed and the blood analyses previously carried out. Food Preservative The apolipoprotein A-IV compounds of the present invention may be made into edible nonionic lipid-soluble additives which are effective antioxidants in food products such as fats, oil, foods, and ingredients of foods without imparting undesirable flavors, aromas, and precipitates. Oxidation of fats, vegetable oils, carotenoids and their biologically active derivatives, Vitamin A, and of essential oUs and other flavorings results in degradation of their quaUty, and is deleterious to foodstuffs containing the oxidized products. The art shows many methods of inhibiting Upid oxidation by adding fat-soluble antioxidants to the substrate. The art does not show the stabiUzation of fats, oUs, fatty foods and ingredients of foods employing apoUpoprotein A-IV and active deriviatives and fragments in a form effective for such purpose. A method of preventing oxidation in a Upid-containing food comprising incorporating in the food an oxidation-inhibiting amount of an apoUpoprotein A-IV compound, derivative, analog, homolog, fragment and mixtures thereof to protect the food from oxidation. GeneraUy, the apoUpoprotein A-IV molecule is a peptide sequence from about 5 to about 90 amino acids in length. The food composition may further comprise carriers, fUlers, and excipients. Preferably, the apoUpoprotein A-IV compound makes up about 0.01% to about 10% of the final weight of the food product. More preferably, the apoUpoprotein A-IV compound makes up from about 0.02% to about 5% of the final weight of the food product. Further, a fat, oil, fatty food or food ingredient substrate stabilized against oxidation with such composition, such a stabilized substrate wherein the substrate includes a carotenoid, and a method of stabilizing a fat, oU, food, or food ingredient substrate which includes the step of introducing into the substrate such a composition as set forth in the foregoing, and such a method wherein the substrate includes a carotenoid. Pharmaceutical Compositions The compositions of the present invention may also be used as a method of preventing oxidation in Upid-containing pharmaceuticals. This embodiment involves incorporating in the pharmaceutical an oxidation-inhibiting amount of an apoUpoprotein A-IV, derivative, analog, homolog, fragment or mixture thereof. GeneraUy, the apoUpoprotein A-IV molecule is a peptide sequence from about 5 to about 90 amino acids in length. The composition may further include carriers, fillers, and excipients. Preferably, the apoUpoprotein A-IV compound makes up about 0.01% to about 25% of the final weight of the pharmaceutical product. More preferably, the apoUpoprotein A-IV compound makes up from about 0.05% to about 10% of the final weight of the pharmaceutical product. Cosmetic or Dermatalogical Preparation In one embodiment, the present invention provides methods of preventing oxidation in a Upid-containing cosmetic or dermatological composition by incorporating, in a suitable vehicle containing cosmetic or dermatological composition, an oxidation- inhibiting amount of an apolipoprotein A-IV compound, derivative, analog, homolog, fragment or mixtures thereof. GeneraUy, the apoUpoprotein A-IV molecule is a peptide sequence from about 5 to about 90 amino acids in length. The composition may further comprise carriers, fillers, and excipients. Preferably, the apolipoprotein A-IV compound is present at a concentration between about 0.005% and about 25% by weight with respect to the total weight of the composition. More preferably, the apoUpoprotein A-IV compound is present at a concentration between about 0.05% and about 10% by weight with respect to the total weight of the composition. In another embodiment, the present invention relates to a new antioxidant system based on an apoUpoprotein A-IV compound, derivative, analog, homolog, fragment or mixtures thereof for use as an antioxidant system in compositions based on an oleaginous material containing such a system and, principaUy, cosmetic compositions. This embodiment generaUy provides for a cosmetic or dermatological composition containing, in a suitable vehicle, an oxidation-inhibiting amount of an apoUpoprotein (apo) A-IV compound, derivative, analog, homolog, fragment or mixtures thereof. GeneraUy, the apoUpoprotein (apo) A-IV molecule is a peptide sequence from about 5 to about 90 amino acids in length. The cosmetic or dermatological composition may be in the form of a suspension or dispersion in a solvent or a fatty substance, or in the form of an emulsion, or in the form of an ointment, a gel, a solid stick or an aerosol foam. The cosmetic or dermatological composition may additionally contain one or more cosmetic adjuvants such as lower alcohols, polyols, esters of, fatty acids, oils, and waxes, solvents, sUicones, thickeners, emollients, UV-A, UV-B and broad band sunscreens, antifoam agents, hydrating agents, perfumes, stabilizers, surfactants, fillers, sequestrants, anionic, cationic, nonionic and amphoteric polymers and mixtures thereof, propellents, alkalifying and acidifying agents, dyes and metal oxide pigments. Preferably, the apolipoprotein A-IV compound is present at a concentration between about 0.001% and about 25% by weight with respect to the total weight of the composition. More preferably, the apoUpoprotein A-IV compound is present at a concentration between about 0.005% and about 15% by weight with respect to the total weight of the composition. In another embodiement, the present invention relates to an antioxidant cosmetic system based on apoUpoprotein A-IV or at least one of its deriviatives or fragments thereof which contains either at least one basic agent or includes at least one tocopherol or a derivative. Preferably the antioxidant system contains from 0.5 to 20 weight percent of a tocopherol or derivative thereof, 0.5 to 50 weight percent of a basic agent and 0.5 to 90 weight percent of apoUpoprotein A-IV and deriviatives and fragments thereof. This antioxidant system is employed in cosmetic or pharmaceutical compositions. The present invention thus relates to a new antioxidant system based on at least one basic agent characterized by the fact that the system also includes at least one tocopherol or a tocopherol derivative and apolipoprotein A-IV compound, derivative, analog, homolog, fragment or mixtures thereof. Sodium hydroxide, triethanolamine, basic amino acid may, for example, be used as the basic agent. By basic amino acid is meant a natural basic amino acid such as, for example, lysine, arginine and histidine, their isomeric or racemic forms, as well as synthetic basic amino acids and derivatives of natural amino acids. Preferably, in accordance with the present invention, lysine or arginine is employed. By the expression "tocopherol" there is meant not only alpha-tocopherol but also beta , gamma or delta tocopherol as well as their mixtures. Among the tocopherol derivatives mention can be made of the esters of tocopherol such as tocopherol acetate and tocopherol nicotinate. According to the invention, the antioxidant system is preferably consisting of: 0.5 to 40 percent of a tocopherol or a tocopherol derivative, 0.5 to 50 percent of a basic amino acid and 0.5 to 90 percent of apoUpoprotein A-IV and deriviatives and fragments thereof. The prefened ratio between the concentration of the basic amino acid and the concentration of the tocopherol ranges from 1 to 20. The compositions according to the invention are provided in the form of oUy solutions, water-in-oU or oU-in-water emulsions, optionaUy anhydrous products, lotions or even microdispersions or ionic or nonionic Upid vesicles. They constitute principaUy milks for the care of the skin, creams (face creams, hand creams, body creams, sunscreen creams, make-up remover creams, foundation creams), foundation fluids, make-up remover milks, sunscreen πdlks, bath oils, Upsticks, eyelid make-up, deodorant sticks, etc. For topical application, the pharmaceutical compositions according to the invention comprise vehicles and ingredients necessary to provide, for example, the composition in the form of ointments, creams, milks, pomades and oily solutions. According to a prefened embodiment, the cosmetic or dermopharrnaceutical compositions are provided in a form intended to be topically appUed and, in particular, creams intended for the protection of the lipids of the skin against oxidation. In the compositions according to the invention, the anti-oxidant system, such as defined above, is generally present such that the following proportions, with respect to the total weight of the composition, are estabUshed: Tocopherol or derivative thereof 0.05 to 2% Basic agent 0.05 to 5% ApoUpoprotein A-IV 0.05 to 8% The compositions of the invention can also contain active compounds or ingredients conventionaUy employed in compositions mentioned above, such as surface active agents, dyes, perfumes, astringent products, ultraviolet absorbing products, organic solvents, water, etc. These compositions are prepared in accordance with conventional methods. The compositions of the invention may also contain, in the aqueous phase, various complementary additives such as preserving agents, sequestering agents, gelling agents and the Uke. The compositions of the invention may also contain, in the Upid phase, various complementary additives such as oUs, waxes or gums having, for example, emoUient or lubricating properties. The compositions are most often provided in milk, cream or gel form, other modes of presentation not being excluded. In another embodiment, the present invention provides a process for the preparation of the compositions described above, comprising: (i) mixing (a) a fatty phase, comprising the UpophiUc surfactant, the hydrophiUc surfactant, and the fatty acid and (b) an aqueous phase comprising the basic agent and the cosmetically or dermatologically active apolipoprotein A-IV compound by stirring to obtain a mixture; and (ii) homogenizing the mixture by subjecting the mixture to cavitation. For cosmetic applications, the compositions of the invention may, moreover, be advantageously used in combination with other compounds displaying retinoid-type activity, with the D vitamins or derivatives thereof, with corticosteroids, with anti-free radical agents, with alpha -hydroxy or alpha-keto acids or derivatives thereof, or alternatively with ion channel blockers, aU of these different active agents. The present invention therefore also features cosmetic compositions comprising a carrier which is cosmeticaUy acceptable and suitable for a topical appUcation and apoUpoprotein A-IV. Such cosmetic compositions are advantageously presented in the form of a cream, a milk, a lotion, a gel, microspheres or nanospheres or Upid or polymeric vesicles, a soap or a shampoo. The concentration of the apoUpoprotein (apo) A-IV compound, derivative, analog, homolog, fragment or mixtures thereof in the cosmetic compositions according to the invention advantageously ranges from 0.001% to 30% by weight relative to the total composition. The medicinal and cosmetic compositions according to the invention may, in addition, contain inert or even pharmacodynamicaUy or cosmetically active additives or combinations of these additives, and, especiaUy: wetting agents; depigmenting agents such as hydroquinone, azelaic acid, caffeic acid or kojic acid; emolUents; moisturizing agents such as glycerol, PEG 400, thiamorpholinone and its derivatives or alternatively urea; antisebonhoeic or antiacne agents such as S-carboxymethylcysteine, S-benzylcysteamine, salts or derivatives thereof, benzoyl peroxide; antibiotics such as erythromycin and esters thereof, neomycin, clindamycin and esters thereof, tetracycUnes; antifungal agents such as ketoconazole or 4,5-polymethylene-3-isothiazolidones; agents promoting hair regrowth, such as MinoxidU (2,4-diamino-6-piperidinopyrimidine 3 -oxide) and derivatives thereof, Diazoxide (7-chloro-3 -methyl- 1,2,4-benzothiadiazine- 1,1 -dioxide) and Phenytoin (5,4- diphenyl-2,4-imidazohdinedione); non-steroidal anti-inflammatory agents; carotenoids and especiaUy beta -carotene; anti-psoriatic agents such as anthralin and derivatives thereof; and, lastly, 5,8,11,14-eicosatetraynoic and 5,8, 11 -eicosatrynoic acids and esters and amides thereof. The compositions according to the invention may also contain taste- or flavor- enhancing agents, preservatives such as parahydroxybenzoic acid esters, stabilizing agents, moisture regulating agents, pH regulating agents, osmotic pressure modifying agents, emulsifying agents, UV- A and UV-B screening agents, antioxidants such as alpha - tocopherol, butylated hydroxyanisole or butylated hydroxytoluene. The foUowing examples lustrate and explain the present invention but should not be taken as limiting the present invention in any regard. Examples. Over-expression of apoUpoprotein (apo) A-IV in transgenic mice confers significant protection against atherosclerosis, despite a more severe atherogenic Upid profile (Duverger, N., Tremp, G., CaiUaud, J. M., etal. Protection against atherogenesis in mice mediated by human apolipoprotein ATV. Science 273, 966-968 (1996); Cohen, R. D., CasteUani, L. W., Qiao, J. H., Lenten, B. J. V., Lusis, A. J. & Reue, K. Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV. J. Clin. Invest. 99, 1906-1916 (1997)). Fasting lymph was used to mimic conditions in the interstitial fluid, a potential site for lipoprotein oxidation in vivo. ApoA-IV greatly inhibited copper induced oxidation of lymph. Using purified LDL as the substrate, the addition of apo A-IV prevented the copper-mediated formation of conjugated dienes. Rat and human apoE or bovine serum albumin offered Uttle protection. ApoA-IV was also effective during the propagation phase of LDL oxidation. The methods of the present invention utilize apoA-IV as a potent endogenous antioxidant. Over-expression of either human or mouse apo A-IV (a plasma protein) in transgenic mice confers significant protection against diet-induced atherosclerosis in cholesterol-fed animals (Duverger, N., Tremp, G., CaiUaud, J. M., et al. Protection against atherogenesis in mice mediated by human apolipoprotein AIV. Science 273, 966-968 (1996); Cohen, R D., CasteUani, L. W., Qiao, J. H., Lenten, B. J. V., Lusis, A J. & Reue, K. Reduced aortic lesions and elevated high density Upoprotein levels in transgenic mice overexpressing mouse apoUpoprotein A-IV. J. Clin. Invest. 99, 1906-1916 (1997)) and also in apoE-deficient mice despite a more severe atherosclerotic lipid profile (Duverger). A hallmark of atherosclerosis is the presence of oxidized lipids in lipoproteins and in the lesions (Chisolm LTI, G. M. & Penn, M. S. in Atherosclerosis and coronary artery disease (eds Fuster, V., Ross, R. & Topol, EJ.) Vol. 1, 129-149 (Lippincott-Raven, Philadelphia, 1996); Berliner, J. A. & Heinecke, J. W. The role of oxidized lipoproteins in atherogenesis. Free Radic. Biol. Med 20, 707-727 (1996)). In this study, we assessed the role of apoA-IV in protecting against lipid oxidation. Initial experiments used fasting intestinal lymph as the substrate to mimic conditions in the interstitial fluid, a potential site of lipoprotein oxidation. Maximal lipid peroxidation (the generation of TBARS) was achieved by incubating the lymph with buffer containing 100 μM Cu 2+ at 37°C for 3 h. Under these experimental conditions, addition of apoA-IV inhibited the oxidation of lymph Upids in a dose-dependent manner (Fig. 1). The anti-oxidative effect was apo A-IV specific as neither BSA nor rat apoE offered any protective effect at 20 μg/ml concentration (data not shown). The inabiUty of apoE to protect against Cu 2+ induced Upid oxidation observed herein is contradictory to previous observation that apoE prevents Upoprotein oxidation (Miyata, M. & Smith, J. D. Apolipoprotein E aUele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nature Genetics 14, 55-61 (1997)). The discrepancy may be explained by differences in experimental conditions of the two studies. One explanation for our observation may be the abiUty of apoA-IV to complex with copper ions, thus preventing divalent cation-induced Upid oxidation events. This is unlikely since excess Cu 2+ , achieved by extensive dialysis of apo A-IV against 100 μM Cu 2+ , failed to overcome the anti-oxidative effects of apoA-IV (data not shown). ApoA- IVs protection against Upid oxidation is physiologicaUy relevant because maximal protection against Upid oxidation was achieved with an apoA-IV concentration that is significantly lower than its lymph (1/10th plasma) and plasma concentration. Apo A-IV was also effective in inhibiting LDL oxidation in a dose-dependent manner (Fig. 1). The fact that apo A-IV inhibits LDL oxidation at 5 μg/ml underscores its potential importance in protecting against atherogenesis by preventing LDL oxidation. The ability of apo A-IV to prevent LDL oxidation was further compared with that of apoE by monitoring the formation of conjugated dienes. As shown in Fig. 2, the addition of 2.5 μg/ml of apo A-IV increased the lag time of Cu 2+ -induced conjugated diene formation in LDL by 3 -fold and 5 μg/ml of apo A-IV totaUy aboUshed conjugated diene formation. In contrast, rat and human apoE (20 μg/ml) increased the lag time of Cu 2+ - induced conjugated diene formation in LDL by only 1.3- and 1.5-fold, respectively (Fig. 2). We also determined if apo A-IV can inhibit LDL oxidation during the propagation phase of the oxidative process. As shown in Fig. 3, addition of apoA-IV during the propagation phase resulted in a dose-dependent inhibition of LDL oxidation. A linear inverse relationship (R 2 = 0.9955) was observed between the rate of conjugated diene formation and the amount of apo A-IV present (Fig. 3 inset), suggesting a direct effect of apoA-IV in interfering with the oxidation process. In conclusion, apoA-IV may play an important role in preventing the oxidation of lipoproteins in vivo. Although many antioxidants exist in nature, apo A-IV is unique because: (i) unlike exogenous anti-oxidants such as a-tocopherol, ascorbate and b- carotene, apoA-IV is synthesized in the body and thus is a natural antioxidant; (ii) apoA- IV's production by the intestine is directly correlated with fat intake; and (in) apo A-IV is amphipathic and is distributed in lipoprotein-bound and lipoprotein-free forms in circulation. In view of observations that apo A-IV is a more potent anti-oxidant than apoE, a well established anti-atherogenic protein, the results suggest that therapeutic treatment aimed at increasing apo A-IV levels may be a fruitful strategy for the reduction of coronary heart disease. Methods Purification of lipoproteins and apoUpoproteins. Human LDL (d = 1.019 - 1.063 g/ml) Mwas isolated from the plasma of normal blood donors by density gradient ultracentrifugation and stored in saUne-EDTA. Before use, EDTA was eliminated by dialysis against PBS. LDL concentration is expressed as mg protein as determined by the Lowry assay. Rat apoUpoproteins were purified from rat plasma as previously described 8 . CoUection of lymph fluid. Intestinal lymph duct of adult male Sprague-Dawley (SD) rats was cannulated. After surgery, rats were infused intraduodenaUy with a glucose-saline solution and intestinal lymph was coUected on ice, and stored at -20° C. Assay of lipid oxidation. Lipid oxidation of lymph and LDL were assayed by the formation of thiobarbituric acid reactive substances (TBARS) (Hulea, S. A, Waswicz, E. & Kummerow, F. A. Inhibition of metal-catalyzed oxidation of low-density Upoprotein by free and albumin-bound biUrubin. Biochim. Biophys. Acta 1259, 29-38 (1995)). Fasting lymph (diluted 20 times) or LDL (50 μg/ml) was oxidized, with or without purified apoUpoproteins, in the presence of 100 or 10 μM CuSO 4 for 3 h at 37°C. In addition, LDL oxidation was also determined by the formation of conjugated dienes (Kleinveld, H. A., Hak-Lemmers, H. L. M., Stalenhoef, A. F. H. & Demacker, P. N. M. Improved measurement of low-density-lipoprotein susceptibility to copper-induced oxidation: Application of a short procedure for isolating low-density lipoprotein. Clin. Chem. 38, 2066-2072 (1992)). LDL (50 μg/ml), with or without additional apoUpoproteins or BSA, was oxidized using 10 μM CuSO at 30°C in a quartz cuvette and absorbance readings at 234 nm were taken every 5 min. SEQUENCE LISTING - - (1) GENERAL INFORMATION: - (ui) NUMBER OF SEQUENCES: 13 - - (2) INFORMATION FOR SEQ ID NO: 1 : - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ID NO: 1: - MetPhel^uLysAlaValValLeuThrValAlaLeuValAlalleThr - GlyTlirGlnAlaGluValThrSerAspGlnValAlaAsnVal - - (2) INFORMATION FOR SEQ ID NO:2: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ID NO: 2: - MetTrpAspTyrPheThrGUiLeuSerAsnAsnAlaLysGluAlaVal - GluGtoLeuGlnLysTlirAspValThrGtaGhiLeuAsnThrLeuPhe - GlnAspLysI^uGlyAsnDeAsnTlirTyrAlaAspAspLeuGlnAsn - LysLeuValProPheAlaValGlnLeuSerGlyHisLeuThrLysGlu - ThrGluArgValArgGluGluIleGlnLysGluLeuGluAspLeuArg - AlaMetVallle; - - (2) INFORMATION FOR SEQ ED NO.3: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: Unear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ED NO: 3 : - MetLeuProHisAlaAsnLysValSerGln - - (2) INFORMATION FOR SEQ ID NO:4: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 14 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ID NO: 4: - MetPheGlyAspAsnVdGlnLysLeuGlnGluHisLeuArgProTyr - AlaTl rAspLeuGlriAlaGlnfleAsnAlaGmTlirGlnAsp - - (2) INFORMATION FOR SEQ ID NO:5: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ID NO: 5: - MetLysArgGlnLeuThrProTyrlleGlnArg - - (2) INFORMATION FOR SEQ ED NO:6: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 16 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ID NO: 6: - MetGlnThrThrlleGlnAspAsnValGluAsnLeuGlnSerSer - - (2) INFORMATION FOR SEQ ED NO:7: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ID NO: 7: - MetValProPheAlaAsnGluLeuLysGluLysPheAsnGlnAsn - - (2) INFORMATION FOR SEQ ID NO:8: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ED NO: 8: - MetGluGlyLeuLysGlyG LeuThrProArgAlaAsnGluLeuLys - AlaThrlleAspGlnAsnLeuGluAspLeuArgSerArgLeuAlaPro - LeuAlaGluGlyValGlnGluLysLeuAsnlleHisGln - - (2) INFORMATION FOR SEQ ID NO: 9: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION. SEQUENCE ID NO: 9: - MetGluGlyLeuAlaPheGln - - (2) INFORMATION FOR SEQ ID NO: 10: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ID NO: 10: - MetLysLysAsnAlaGluGluLeuHisThrLysValSerThrAsnlle - AspGlnLeuGlnLys AsnLeu AlaProLeu ValGlu Asp ValGlnS er - LysLeuLysGlyAsnThrGluGlyLeuGlnLysSerLeuGluAspLeu - AsnLysGlnLeuAspGlnGlnValGluValPheArgArgAlaValGlu - ProLeuGlyAspLysPheAsn - - (2) INFORMATION FOR SEQ ID NO: 11 : - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ED NO: 11: - MetAlaLeuValGlnGln - - (2) INFORMATION FOR SEQ ID NO: 12: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: Unear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ID NO: 12: - MetGluLysPheArgGlnGlnLeuGlySerAspSerGlyAspValGlu - SerHisLeuSerPheLeuGluLysAsnLeuArgGluLysValSerSer Phe - - (2) INFORMATION FOR SEQ ED NO: 13: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ID NO: 13: - MetSerThrl^uGUiLysLysGlySerProAspGlnProLeuAlaLeu - ProLeuProGluGlnValGlnGluGmValGlnGluGlnValGUiPro - LysProLeuGluSer (2) INFORMATION FOR SEQ JD NO: 14: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ID NO: 14: - - (2) INFORMATION FOR SEQ ID NO: 15: - (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear - (xi) SEQUENCE DESCRIPTION: SEQUENCE ED NO: 15:

Claims: CLAIMS. What is claimed is: 1. A method of treating conditions associated with Upid oxidation, comprising: administering a composition comprising a pharmacologicaUy effective amount of an apoUpoprotein (apo) A-FV compound. 2. A method according to claim 1 wherein the apoUpoprotein (apo) A-EV compound is selected from the group consisting of apoUpoprotein (apo) A-FV, derivatives, analogs, homologs, fragments and mixtures thereof. 3. A method according to claim 2 wherein the apoUpoprotein (apo) A-IV molecule is a peptide sequence from about 5 to about 90 amino acids in length. 4. A method according to claim 3 wherein the peptide has an amino acid sequence selected from the group comprising: Met-Phe-Leu-Lys-Ala-Val-Val-Leu-Thr-Val-Ala-Leu-Val-Ala-Ile-Thr-Gly-Thr-Gln- Ala-Glu-Val-Thr-Ser- Asp-Gin- Val-Ala-Asn-Val (SEQ ED NO: l); Met-Trp-Asp-Tyr-Phe-Thr-Gln-Leu-Ser-Asn-Asn-Ala-Lys-Glu-Ala-Val-Glu-Gln-Leu- Gln-Lys-Thr-Asp-Val-Thr-Gln-Gln-Leu-Asn-Thr-Leu-Phe-Gln-Asp-Lys-Leu-Gly- Asn-Ile-Asn-Thr-Tyr-Ala-Asp-Asp-Leu-Gln-Asn-Lys-Leu-Val-Pro-Phe-Ala-Val-Gm- Leu-Ser-Gly-His-Leu-Thr-Lys-Glu-Thr-Glu-Arg-Val-Arg-Glu-Glu-Ile-Gln-Lys-Glu- Leu-Glu-Asp-Leu-Arg-Ala-Met-Val-Ile (SEQ ED NO:2); Met-Leu-Pro-His-Ala-Asn-Lys-Val-Ser-Gln (SEQ JD NO:3); Met-Phe-Gly-Asp-Asn-V -Gta-Lys-I^u-Gln-Glu-His-Leu-Arg-Pro-Tyr-Ala-Thr-Asp- Leu-Gln-Ala-Gln-Ile-Asn-Ala-Gln-Thr-Gln-Asp (SEQ JD NO:4); Met-Lys-Arg-Gln-Leu-Thr-Pro-Tyr-Ile-Ghi-Arg (SEQ JD NO: 5); Met-Gln-Thr-Thr-fle-Gln-Asp-Asn-Val-Glu-Asn-Leu-Gm-Ser-Ser (SEQ ID NO:6); Met-Val-Pro-Phe-Ala-Asn-Glu-Leu-Lys-Glu-Lys-Phe-Asn-Gln-Asn (SEQ ED NO:7); Met-Glu-Gly-Leu-Lys-Gly-Gm-Leu-Thr-Pro-Arg-Ala-Asn-Glu-Leu-Lys-Ala-Thr-Ile- Asp-Gln-Asn-Leu-Glu-Asp-Leu-Arg-Ser-Arg-Leu-Ala-Pro-Leu-Ala-Glu-Gly-Val- Gln-Glu-Lys-Leu-Asn-Ile-His-Gln (SEQ ID NO: 8); Met-Glu-Gly-Leu-Ala-Phe-Gln (SEQ EO NO:9); Met-Lys-Lys-Asn-Ala-Glu-Glu-Leu-His-Thr-Lys-Val-Ser-Thr-Asn-Ile-Asp-Gln-Leu- Gln-Lys-Asn-Leu-Ala-Pro-Leu-Val-Glu-Asp-Val-GUi-Ser-Lys-Leu-Lys-Gly-Asn-Thr- Glu-Gly-Leu-Gln-Lys-Ser-Leu-Glu-Asp-Leu-Asn-Lys-Gln-Leu-Asp-Gln-Gln-Val- Glu-Val-Phe-Arg-Arg-Ala-Val-Glu-Pro-Leu-Gly-Asp-Lys-Phe-Asn (SEQ ID NO: 10); Met- Ala-Leu- Val-Gln-Gln (SEQ ID NO: 11), Met-Glu-Lys-Phe-Arg-Gln-Gln-Leu-Gly-Ser-Asp-Ser-Gly-Asp-Val-Glu-Ser-His-Leu- Ser-Phe-Leu-Glu-Lys-Asn-Leu-Arg-Glu-Lys-Val-Ser-Ser-Phe (SEQ ID NO: 12); Met-Ser-Thr-Leu-Gln-Lys-Lys-Gly-Ser-Pro-Asp-Gln-Pro-Leu-Ala-Leu-Pro-Leu-Pro- Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Pro-Lys-Pro-Leu-Glu-Ser (SEQ LD NO:13); derivatives, analogs, homologs, fragments and mixtures thereof. 5. A method according to claim 3 wherein the composition further comprises at least one ingredient selected from the group consisting of carriers, fiUers, and excipients. 6. A method according to claim 3 wherein the composition further comprises a UpophiUc compound. 7. A method according to claim 6 wherein the UpophiUc compound is selected from the group consisting of organic solvents, phosphatidyl choline, cholesterol and mixtures thereof. 8. A method according to claim 2 wherein the administering comprises oral administering. 9. A method according to claim 2 wherein the administering comprises parenteral administering. 10. A method according to claim 9 wherein the administering is a dosing method selected from the group consisting of transdermai administering, subcutaneous injecting, intravenous injecting, intraperitoneal injecting, intramuscular injecting, intrasternal injection, intrathecal injection, intraventricular injecting, intracerebroventricular injecting, and infusing. 11. A method according to claim 2 wherein the composition is administered in a unitary dose of from about 1 to about 1000 mg. 12. A method according to claims 11 wherein the unitary dose in administered from about 1 to about 3 time a day. 13. A method of inhibiting the progression of atherosclerosis in a patient in need thereof comprising administering to the patient an effective anti-oxidation amount of a compound of claim 1. 14. A method of treating a patient for atherosclerosis comprising administering to the patient an effective anti-oxidation amount of a compound of claim 2. 15. The method of claim 3 wherein said peptide comprises: Met-Phe-Leu-Lys-Ala-Val- Val-Leu-Tlιr-V -Ala-Leu-Val-Ala-πe-Tlιr-Gly-Thr-Gln-Ala-Glu-Val-Thr-Ser-Asp- Gln-Val-Ala-Asn-Val (SEQ ID NO: 1); 16. The method of claim 3 wherein said peptide comprises: Met-Trp-Asp-Tyr-Phe-Thr- Gta-I u-Ser-Asn-Asn-Ala-Lys-Glu-Ala-Val-Glu-Gm-Leu-Gln-Lys-Thr-Asp-Val-Thr- Gm-Gm-I u-Asn-Tlir-I^u-Phe-Gln-Asp-Lys-I u-Gly-Asn-fle-Asn-Thr-Tyr-Ala-Asp- Asp-Leu-GUi-Asn-Lys-Leu-Val-Pro-Phe-Ala-Val-Gln-Leu-Ser-Gly-His-Leu-Thr-Lys- Glu-Thr-Glu-Arg-Val-Arg-Glu-Glu-Ile-Gln-Lys-Glu-Leu-Glu-Asp-Leu-Arg-Ala-Met- Val-Ile (SEQ ED NO:2); 17. The method of claim 3 wherein said peptide comprises: Met-Leu-Pro-His-Ala-Asn- Lys-Val-Ser-Gln (SEQ ID NO:3); 18. The method of claim 3 wherein said peptide comprises: Met-Phe-Gly-Asp-Asn-Val- Gln-Lys-Leu-Gln-Glu-His-Leu-Arg-Pro-Tyr-Ala-Thr-Asp-Leu-Gln-Ala-Gln-Ile-Asn- Ala-Gln-Thr-Gln-Asp (SEQ ID NO:4); 19. The method of claim 3 wherein said peptide comprises: Met-Lys-Arg-Gln-Leu-Thr- Pro-Tyr-Ile-Gln- Arg (SEQ ID NO: 5); 20. The method of claim 3 wherein said peptide comprises: Met-Gln-Thr-Thr-Ile-Gln- Asp-Asn-Val-Glu-Asn-Leu-Gln-Ser-Ser (SEQ ED NO:6); 21. The method of claim 3 wherein said peptide comprises: Met-Val-Pro-Phe-Ala-Asn- Glu-Leu-Lys-Glu-Lys-Phe-Asn-Gln-Asn (SEQ JD NO:7); 22. The method of claim 3 wherein said peptide comprises: Met-Glu-Gly-Leu-Lys-Gly- Gm-I^u-Thr-Pro-Arg-Ala-Asn-Glu-Leu-Lys-Ala-Thr-Ile-Asp-Gm-Asn-Leu-Glu-Asp- Leu-Arg-Ser-Arg-Leu-Ala-Pro-Leu-Ala-Glu-Gly-Val-Gm-Glu-Lys-Leu-Asn-Ile-His- Gln (SEQ FD NO:8); 23. The method of claim 3 wherein said peptide comprises: Met-Glu-Gly-Leu-Ala-Phe- Gin (SEQ ED NO:9); 24. The method of claim 3 wherein said peptide comprises: Met-Lys-Lys-Asn-Ala-Glu- Glu-I^u-His-Thr-Lys-Val-Ser-Thr-Asn-Ile-Asp-Gln-Leu-Gln-Lys-Asn-Leu-Ala-Pro- Leu-Val-Glu-Asp-Val-Gln-Ser-Lys-Leu-Lys-Gly-Asn-Thr-Glu-Gly-Leu-Gln-Lys-Ser- Leu-Glu-Asp-Leu-Asn-Lys-Gln-Leu-Asp-Gln-Gln-Val-Glu-Val-Phe-Arg-Arg-Ala- Val-Glu-Pro-Leu-Gly-Asp-Lys-Phe-Asn (SEQ JD NO: 10); 25. The method of claim 3 wherein said peptide comprises: Met- Ala-Leu- Val-Gln-Gln (SEQ ED NO: 11); 26. The method of claim 3 wherein said peptide comprises: Met-Glu-Lys-Phe-Arg-Gln- Gln-Leu-Gly-Ser-Asp-Ser-Gly-Asp-Val-Glu-Ser-His-Leu-Ser-Phe-Leu-Glu-Lys-Asn- Leu-Arg-Glu-Lys-Val-Ser-Ser-Phe (SEQ ED NO: 12); 27. The method of claim 3 wherein said peptide comprises: Met-Ser-Thr-Leu-Gln-Lys- Lys-Gly-Ser-Pro-Asp-Gln-Pro-Leu-Ala-Leu-Pro-Leu-Pro-Glu-Gln-Val-Gln-Glu-Gln- Val-Gln-Glu-Gln-Val-Gln-Pro-Lys-Pro-Leu-Glu-Ser (SEQ DO NO: 13); 28. A method of preventing oxidation in a Upid-containing food comprising incorporating in the food an oxidation-inhibiting amount of an apoUpoprotein (apo) A-FV compound to protect the food from oxidation. 29. A method according to claim 28 wherein the apoUpoprotein (apo) A-FV compound is selected from the group consisting of apoUpoprotein (apo) A-FV, derivatives, analogs, homologs, fragments and mixtures thereof. 30. A method according to claim 29 wherein the apoUpoprotein (apo) A-FV molecule is a peptide sequence from about 5 to about 90 amino acids in length. 31. A method according to claim 30 wherein the peptide has an amino acid sequence selected from the group comprising: Met-Phe-Leu-Lys-Ala-Vd-Val-I^u-Tlir-Val-Ala-Leu-Val-A a-Ile-Thr-Gly-Thr-Gln- Ala-Glu-Val-Thr-Ser- Asp-Gin- Val-Ala-Asn-Val (SEQ ED NO: l); Met-Trp-Asp-Tyr-Phe-Thr-Gln-Leu-Ser-Asn-Asn-Ala-Lys-Glu-Ala-Val-Glu-Gln-Leu- Gln-Lys-Thr-Asp-Val-Thr-Gln-Gln-Leu-Asn-Thr-Leu-Phe-Gln-Asp-Lys-Leu-Gly- Asn-De-Asn-Thr-Tyr-Ala-Asp-Asp-Leu-Gln-Asn-Lys-Leu-Val-Pro-Phe-Ala-Val-Gm- Leu-Ser-Gly-His-Leu-Thr-Lys-Glu-Thr-Glu-Arg-Val-Arg-Glu-Glu-Ile-GU -Lys-Glu- Leu-Glu-Asp-Leu-Arg-Ala-Met- Val-Ile (SEQ ED NO:2); Met-Leu-Pro-His-Ala-Asn-Lys-Val-Ser-Gln (SEQ JD NO:3); Met-Phe-Gly-Asp-Asn-Val-Gln-Lys-Leu-Gln-Glu-His-Leu-Arg-Pro-Tyr-Ala-Thr-Asp- Leu-Gln-Ala-Gln-Ile-Asn-Ala-Gln-Thr-Gln-Asp (SEQ JD NO:4); Met-Lys-Arg-Gln-Leu-Thr-Pro-Tyr-Ile-Gln-Arg (SEQ ED NO: 5); Met-Gln-Thr-Thr-Ile-Gln-Asp-Asn-Val-Glu-Asn-Leu-Gln-Ser-Ser (SEQ LD NO:6); Met-Val-Pro-Phe-Ala-Asn-Glu-Leu-Lys-Glu-Lys-Phe-Asn-Gln-Asn (SEQ ID NO:7); Met-Glu-Gly-Leu-Lys-Gly-Gln-Leu-Thr-Pro-Arg-Ala-Asn-Glu-Leu-Lys-Ala-Thr-Ile- Asp-Gln-Asn-Leu-Glu-Asp-Leu-Arg-Ser-Arg-Leu-Ala-Pro-Leu-Ala-Glu-Gly-Val- Gln-Glu-Lys-Leu-Asn-He-His-Gln (SEQ ED NO: 8); Met-Glu-Gly-Leu-Ala-Phe-Gln (SEQ ID NO:9); Met-Lys-Lys-Asn-Ala-Glu-Glu-Leu-His-Thr-Lys-Val-Ser-Thr-Asn-Ile-Asp-Gln-Leu- G -Lys-Asn-I^u-Ala-Pro-I^u-V -Glu-Asp-Val-Gm-Ser-Lys-Leu-Lys-Gly-Asn-Thr- Glu-Gly-I^u-Gln-Lys-Ser-Leu-Glu-Asp-Leu-Asn-Lys-Gm-Leu-Asp-GUi-Gln-Val- Glu-Val-Phe-Arg-Arg-Ala-Val-Glu-Pro-Leu-Gly-Asp-Lys-Phe-Asn (SEQ ID NO: 10); Met-Ala-Leu-Val-Gln-Gln (SEQ ID NO: 11); Met-Glu-Lys-Phe-Arg-Gln-Gln-Leu-Gly-Ser-Asp-Ser-Gly-Asp-Val-Glu-Ser-His-Leu- Ser-Phe-Leu-Glu-Lys-Asn-Leu-Arg-Glu-Lys-Val-Ser-Ser-Phe (SEQ ID NO: 12); Met-Ser-Thr-Leu-Gln-Lys-Lys-Gly-Ser-Pro-Asp-GUi-Pro-Leu-Ala-Leu-Pro-Leu-Pro- Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Pro-Lys-Pro-Leu-Glu-Ser (SEQ ID NO:13); and derivatives, analogs, homologs, fragments and mixtures thereof. 32. A method according to claim 29 wherein the composition further comprises at least one ingredient selected from the group consisting of carriers, fillers, and excipients. 33. A method according to claim 29 wherein the apolipoprotein A-IV compound makes up about 0.01% to about 10% of the final weight of the food product. 34. A method according to claim 28 wherein the apolipoprotein A-IV compound makes up about 0.02% to about 5% of the final weight of the food product. 35. A method of preventing oxidation in a Upid-containing pharmaceutical comprising incorporating in the pharmaceutical an oxidation-inhibiting amount of an apoUpoprotein (apo) A-IV compound to protect the pharmaceutical from oxidation. 36. A method according to claim 35 wherein the apoUpoprotein (apo) A-FV compound is selected from the group consisting of apoUpoprotein (apo) A-IV, derivatives, analogs, homologs, fragments and mixtures thereof. 37. A method according to claim 36 wherein the apoUpoprotein (apo) A-FV molecule is a peptide sequence from about 5 to about 90 amino acids in length. 38. A method according to claim 37 wherein the peptide has an amino acid sequence selected from the group comprising: Met-Phe-Leu-Lys-Ala-Val-Val-Leu-Thr-Val-Ala-Leu-Val-Ala-πe-Thr-Gly-Thr-Gln- Ala-Glu-Val-Thr-Ser-Asp-Gln-Val-Ala-Asn-Val (SEQ JD NO:l); Met-Trp-Asp-Tyr-Phe-Thr-Gln-Leu-Ser-Asn-Asn-Ala-Lys-Glu-Ala-Val-Glu-GUi-Leu- Gln-Lys-Thr-Asp-Val-Thr-Gln-Gln-Leu-Asn-Thr-Leu-Phe-Gln-Asp-Lys-Leu-Gly- Asn-Ile-Asn-Thr-Tyr-Ala-Asp-Asp-Leu-Gln-Asn-Lys-Leu-Val-Pro-Phe-Ala-Val-Gln- Leu-Ser-Gly-His-Leu-Thr-Lys-Glu-Thr-Glu-Arg-Val-Arg-Glu-Glu-Ile-Gln-Lys-Glu- Leu-Glu-Asp-Leu-Arg-Ala-Met- Val-Ile (SEQ ID NO:2); Met-Leu-Pro-His-Ala-Asn-Lys-Val-Ser-Gln (SEQ LD NO:3); Met-Phe-Gly-Asp-Asn-Val-Gln-Lys-Leu-Gln-Glu-His-Leu-Arg-Pro-Tyr-Ala-Thr-Asp- Leu-Gln-Ala-Gln-fle-Asn-Ala-Gln-Thr-Gln-Asp (SEQ ED NO:4); Met-Lys-Arg-Gln-Leu-Thr-Pro-Tyr-Ile-Gln-Arg (SEQ ID NO: 5); Met-Gln-Thr-Thr-Ile-Gln-Asp-Asn-Val-Glu-Asn-Leu-Gln-Ser-Ser (SEQ ED NO: 6); Met- Val-Pro-Phe-Ala-Asn-Glu-Leu-Lys-Glu-Lys-Phe-Asn-Gln- Asn (SEQ ID NO: 7); Met-Glu-Gly-Leu-Lys-Gly-Gln-Leu-Thr-Pro-Arg-Ala-Asn-Glu-Leu-Lys-Ala-Thr-Ile- Asp-Gln-Asn-Leu-Glu-Asp-Leu-Arg-Ser-Arg-Leu-Ala-Pro-Leu-Ala-Glu-Gly-Val- GUi-Glu-Lys-Leu-Asn-Ile-His-Gm (SEQ ID NO: 8); Met-Glu-Gly-Leu-Ala-Phe-Gln (SEQ ID NO:9); Met-Lys-Lys-Asn-Ala-Glu-Glu-Leu-His-Tlir-Lys-V -Ser-Thr-Asn-Ile-Asp-Gln-Leu- Gln-Lys-Asn-Leu-Ala-Pro-Leu-Val-Glu-Asp-Val-Gm-Ser-Lys-Leu-Lys-Gly-Asn-Thr- Glu-G y-Leu-Gln-Lys-Ser-Leu-Glu-Asp-Leu-Asn-Lys-Gln-Leu-Asp-GUi-Gln-Val- Glu-Val-Phe-Arg-Arg-Ala-Val-Glu-Pro-Leu-Gly-Asp-Lys-Phe-Asn (SEQ ID NO: 10); Met-Ala-Leu-Val-Gln-Gln (SEQ JD NO: 11); Met-Glu-Lys-Phe-Arg-Gln-Gln-Leu-Gly-Ser-Asp-Ser-Gly-Asp-Val-Glu-Ser-His-Leu- Ser-Phe-Leu-Glu-Lys-Asn-Leu-Arg-Glu-Lys-Val-Ser-Ser-Phe (SEQ ID NO: 12); Met-Ser-Thr-Leu-GUi-Lys-Lys-Gly-Ser-Pro-Asp-GUi-Pro-Leu-Ala-Leu-Pro-Leu-Pro- Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Pro-Lys-Pro-Leu-Glu-Ser (SEQ LD NO: 13); and derivatives, analogs, homologs, fragments and mixtures thereof. 39. A method according to claim 38 wherein the composition further comprises at least one ingredient selected from the group consisting of carriers, fillers, and excipients. 40. A method according to claim 38 wherein the Apolipoprotein A-IV compound makes up about 0.01 to about 25% of the final weight of the pharmaceutical product. 41. A method according to claim 38 wherein the apolipoprotein A-IV compound makes up about 0.05% to about 10% of the final weight of the pharmaceutical product. 42. A method of preventing oxidation using a cosmetic or dermatological composition comprising incorporating, in a suitable vehicle containing cosmetic or dermatological composition, an oxidation-inhibiting amount of an apoUpoprotein (apo) A-IV compound to protect the containing cosmetic or dermatological composition from oxidation. 43. A method according to claim 42 wherein the apoUpoprotein (apo) A-FV compound is selected from the group consisting of apoUpoprotein (apo) A-IV, derivatives, analogs, homologs, fragments and mixtures thereof. 44. A method according to claim 43 wherein the apoUpoprotein (apo) A-FV molecule is a peptide sequence from about 5 to about 90 amino acids in length. 45. A method according to claim 44 wherein the peptide has an amino acid sequence selected from the group comprising: Met-Phe-Leu-Lys-Ala-Val-Val-Leu-Thr-Val-Ala-Leu-Val-Ala-fle-Thr-Gly-Thr-Gln- Ala-Glu-Val-Thr-Ser-Asp-Gln-Val-Ala-Asn-Val (SEQ ID NO:l); Met-Trp-Asp-Tyr-Phe-Thr-Gln-Leu-Ser-Asn-Asn-Ala-Lys-Giu-Ala-Val-Glu-Gln-Leu- Gln-Lys-Thr-Asp-Val-Thr-Gln-Gln-Leu-Asn-Thr-Leu-Phe-Gln-Asp-Lys-Leu-Gly- Asn-Ile-Asn-Thr-Tyr-Ala-Asp-Asp-Leu-G -Asn-Lys-Leu-Val-Pro-Phe-Ala-Val-Gln- Leu-Ser-Gly-His-Leu-Thr-Lys-Glu-Thr-Glu-Arg-Val-Arg-Glu-Glu-Ile-Gln-Lys-Glu- Leu-Glu-Asp-Leu-Arg-Ala-Met- Val-Ile (SEQ JD NO:2); Met-Leu-Pro-His-Ala-Asn-Lys-Val-Ser-Gln (SEQ ED NO:3); Met-Phe-Gly-Asp-Asn-Val-Gln-Lys-Leu-Gln-Glu-His-Leu-Arg-Pro-Tyr-Ala-Thr-Asp- Leu-Gln-Ala-Gln-Ile-Asn-Ala-Gln-Thr-Gln-Asp (SEQ ID NO:4); Met-Lys-Arg-Gln-Leu-Thr-Pro-Tyr-Ile-Gln-Arg (SEQ ID NO: 5); Met-Gln-Thr-Thr-Ile-Gln-Asp-Asn-Val-Glu-Asn-Leu-Gln-Ser-Ser (SEQ ID NO:6); Met-Val-Pro-Phe-Ala-Asn-Glu-Leu-Lys-Glu-Lys-Phe-Asn-Gln-Asn (SEQ ID NO: 7); Met-Glu-Gly-Leu-Lys-Giy-Gln-Leu-Thr-Pro-Arg-Ala-Asn-Glu-Leu-Lys-Ala-Thr-Ile- Asp-Gm-Asn-Leu-Glu-Asp-Leu-Arg-Ser-Arg-Leu-Ala-Pro-Leu-Ala-Glu-Gly-Val- Gln-Glu-Lys-Leu-Asn-Ile-His-Gln (SEQ ID NO: 8); Met-Glu-Gly-Leu-Ala-Phe-Gln (SEQ ID NO:9); Met-Lys-Lys-Asn-Ala-Glu-Glu-I^u-His-Thr-Lys-Val-Ser-Thr-Asn-Ile-Asp-Gln-Leu- GUi-Lys-Asn-Leu-Ala-Pro-Leu-Val-Glu-Asp-Val-Ghi-Ser-Lys-Leu-Lys-Gly-Asn-Thr- Glu-Gly-Leu-Gln-Lys-Ser-Leu-Glu-Asp-Leu-Asn-Lys-GUi-Leu-Asp-GUi-GU -Val- Glu-Val-Phe-Arg-Arg-Ala-Val-Glu-Pro-Leu-Gly-Asp-Lys-Phe-Asn (SEQ JD NO: 10); Met-Ala-Leu-Val-Gln-Gln (SEQ ID NO: 11); Met-Glu-Lys-Phe-Arg-Gln-Gln-Leu-Gly-Ser-Asp-Ser-Gly-Asp-Val-Glu-Ser-His-Leu- Ser-Phe-Leu-Glu-Lys-Asn-Leu-Arg-Glu-Lys-Val-Ser-Ser-Phe (SEQ ID NO: 12); Met-Ser-Thr-Leu-Ghi-Lys-Lys-Gly-Ser-Pro-Asp-Gln-Pro-Leu-Ala-Leu-Pro-Leu-Pro- Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Pro-Lys-Pro-Leu-Glu-Ser (SEQ ID NO: 13); and derivatives, analogs, homologs, fragments and mixtures thereof. 46. A method according to claim 45 wherein the composition further comprises at least one ingredient selected from the group consisting of carriers, fillers, and excipients. 47. A method according to claim 45 wherein the apolipoprotein (apo) A-IV compound is present at a concentration between about 0.005% and about 25% by weight with respect to the total weight of the composition. 48. A method according to claim 45 wherein the apolipoprotein (apo) A-IV compound is present at a concentration between about 0.05% and about 10% by weight with respect to the total weight of the composition. 49. A cosmetic or dermatological composition containing, in a suitable vehicle, an oxidation-inhibiting amount of an apoUpoprotein (apo) A-IV compound. 50. A composition according to claim 49 wherein the apoUpoprotein (apo) A-IV compound is selected from the group consisting of apoUpoprotein (apo) A-FV, derivatives, analogs, homologs, fragments and mixtures thereof. 51. A composition according to claim 50 wherein the apoUpoprotein (apo) A-FV molecule is a peptide sequence from about 5 to about 90 amino acids in length. 52. A composition according to claim 51 wherein the peptide has an amino acid sequence selected from the group comprising: Met-Phe-Leu-Lys-Ala-V -Vd-Leu-Tlir-V -Ala-Leu-V -Ala-πe-Thr-Gly-Thr-Gln- Ala-Glu-Val-Thr-Ser-Asp-Gln-Val-Ala-Asn-Val (SEQ ID NO:l); Met-T -Asp-Tyr-Phe-Thr-Gln-Leu-Ser-Asn-Asn-Ala-Lys-Glu-Ala-Val-Glu-Gln-Leu- Gln-Lys-Thr-Asp-Val-Thr-Gln-Gln-Leu-Asn-Thr-Leu-Phe-Gln-Asp-Lys-Leu-Gly- Asn-Ile-Asn-Thr-Tyr-Ala-Asp-Asp-Leu-Gln-Asn-Lys-Leu-Val-Pro-Phe-Ala-Val-Gln- Leu-Ser-Gly-His-Leu-Thr-Lys-Glu-Thr-Glu-Arg-Val-Arg-Glu-Glu-Ile-Gln-Lys-Glu- Leu-Glu-Asp-Leu-Arg-Ala-Met- Val-Ile (SEQ ID NO:2); Met-Leu-Pro-His-Ala-Asn-Lys-Val-Ser-Gln (SEQ JD NO: 3); Met-Phe-Gly-Asp-Asn-Val-Gln-Lys-Leu-Gln-Glu-His-Leu-Arg-Pro-Tyr-Ala-Thr-Asp- Leu-Gln-Ala-Gln-Ile-Asn-Ala-Gln-Thr-Gln-Asp (SEQ ED NO:4); Met-Lys-Arg-Gln-Leu-Thr-Pro-Tyr-Ile-Gln-Arg (SEQ ID NO: 5); Met-Gln-Thr-Thr-Ile-Gln-Asp-Asn-Val-Glu-Asn-Leu-Gln-Ser-Ser (SEQ ID NO:6); Met-Val-Pro-Phe-Ala-Asn-Glu-Leu-Lys-Glu-Lys-Phe-Asn-Gln-Asn (SEQ ID NO:7); Met-Glu-Gly-Leu-Lys-Gly-Gln-Leu-Thr-Pro-Arg-Ala-Asn-Glu-Leu-Lys-Ala-Thr-Ile- Asp-Gln-Asn-Leu-Glu-Asp-Leu-Arg-Ser-Arg-Leu-Ala-Pro-Leu-Ala-Glu-Gly-Val- Gln-Glu-Lys-Leu-Asn-Ile-His-Gln (SEQ ID NO: 8); Met-Glu-Gly-Leu-Ala-Phe-Gln (SEQ JD NO:9); Met-Lys-Lys-Asn-Ala-Glu-Glu-Leu-His-Thr-Lys-Val-Ser-Thr-Asn-Ile-Asp-Gln-Leu- Gln-Lys-Asn-Leu-Ala-Pro-Leu-Val-Glu-Asp-Val-GUi-Ser-Lys-Leu-Lys-Gly-Asn-Thr- GUu-Gly-Leu-Gln-Lys-Ser-Leu-Glu-Asp-Leu-Asn-Lys-Gln-Leu-Asp-Gln-Gto-Val- Glu-Val-Phe-Arg-Arg-Ala-Val-Glu-Pro-Leu-Gly-Asp-Lys-Phe-Asn (SEQ FD NO: 10); Met-Ala-Leu-Val-Gln-Gln (SEQ ED NO: 11); Met-Glu-Lys-Phe-Arg-Gln-Gln-Leu-Gly-Ser-Asp-Ser-Gly-Asp-Val-Glu-Ser-His-Leu- Ser-Phe-Leu-Glu-Lys-Asn-Leu-Arg-Glu-Lys-Val-Ser-Ser-Phe (SEQ ED NO: 12); Met-Ser-Thr-Leu-Gln-Lys-Lys-Gly-Ser-Pro-Asp-Gln-Pro-Leu-Ala-Leu-Pro-Leu-Pro- Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Glu-Gln-Val-Gln-Pro-Lys-Pro-Leu-Glu-Ser (SEQ ED NO: 13); and derivatives, analogs, homologs, fragments and mixtures thereof. 53. The cosmetic or dermatological composition of claim 52 wherein the composition is in the form of a suspension or dispersion in a solvent or a fatty substance, or in the form of an emulsion, or in the form of an ointment, a gel, a solid stick or an aerosol foam. 54. The cosmetic or dermatological composition of claim 52 in a form wherein the cosmetically acceptable carrier is selected from the group consisting of a lotion, a gel, a cream, a milk, a powder, a soUd stick, a foam and a spray. 55. The cosmetic or dermatological composition according to claim 52, wherein the composition additionaUy contains cosmetic adjuvants selected from the group consisting of lower alcohols, polyols, esters of, fatty acids, oUs, and waxes, solvents, siUcones, thickeners, emoUients, UV-A, UV-B and broad band sunscreens, antifoam agents, hydrating agents, perfumes, stabilizers, surfactants, fUlers, sequestrants, anionic, cationic, nonionic and amphoteric polymers and mixtures thereof, propeUants, alkalifying and acidifying agents, dyes and metal oxide pigments. 56. The composition according to claim 52, wherein the apoUpoprotein A-FV compound is present at a concentration between about 0.005% and about 15% by weight with respect to the total weight of the composition. 57. The cosmetic or dermatological composition of claim 52 which further contains either at least one basic agent or includes at least one tocopherol or a derivative. 58. The cosmetic or dermatological composition of claim 57 wherein the composition contains from about 0.5 to about 20 weight percent of a tocopherol or derivative thereof, about 0.5 to about 50 weight percent of a basic agent and about 0.5 to about 90 weight percent of the apolipoprotein A-FV compound. 59. The cosmetic or dermatological composition of claim 58 wherein the basic agent is selected from the group consisting of sodium hydroxide, triethanolamine, a basic amino acid, such as lysine or arginine and mixtures thereof. 60. The cosmetic or dermatological composition of claim 57 wherein the composition contains from about 0.05 to about 2.0 weight percent of a tocopherol or derivative thereof, about 0.05 to about 5.0 weight percent of a basic agent and about 0.05 to about 9.0 weight percent of the apolipoprotein A-IV compound. 61. The cosmetic or dermatological composition of claim 57 wherein the composition additionaUy contains one or more compounds selected from the group consisting of wetting agents; depigmenting agents such as hydroquinone, azelaic acid, caffeic acid or kojic acid; emolUents; moisturizing agents such as glycerol, PEG 400, thiamorphoUnone and its derivatives or alternatively urea; antiseborrhoeic or antiacne agents such as S-carboxymethylcysteine, S-benzylcysteamine, salts or derivatives thereof, benzoyl peroxide; antibiotics such as erythromycin and esters thereof, neomycin, clindamycin and esters thereof, tetracyclines; antifungal agents such as ketoconazole or 4,5-polymethylene-3-isothiazoUdones; agents promoting hair regrowth, such as Minoxidil (2,4-diammo-6-piperidinopyrimidine 3 -oxide) and derivatives thereof, Diazoxide (7-chloro-3 -methyl- 1,2,4-benzothiadiazine- 1,1 -dioxide) and Phenytoin (5,4-diphenyl-2,4-imidazolidinedione); non-steroidal anti-inflammatory agents; carotenoids and especially beta -carotene; anti-psoriatic agents such as anthralin and derivatives thereof; 5,8,11,14-eicosatetraynoic and 5,8,11-eicosatrynoic acids and esters and amides thereof; taste- or flavor-enhancing agents; preservatives such as parahydroxybenzoic acid esters; stabilizing agents; moisture regulating agents; pH regulating agents; osmotic pressure modifying agents; emulsifying agents; UV-A and UV-B screening agents; and other antioxidants such as alpha -tocopherol, butylated hydroxyanisole or butylated hydroxytoluene. 62. Cosmetic composition according to claim 60, wherein the composition additionally contains cosmetic adjuvants selected from the group consisting of lower alcohols, polyols, esters of, fatty acids, oils, and waxes, solvents, siUcones, thickeners, emolUents, UV-A, UV-B and broad band sunscreens, antifoam agents, hydrating agents, perfumes, stabilizers, surfactants, fillers, sequestrants, anionic, cationic, nonionic and amphoteric polymers and mixtures thereof, propeUants, alkaUfying and acidifying agents, dyes and metal oxide pigments.

Inventors: HUI DAVID Y, TSO PATRICK, HUI, DAVID, Y., TSO, PATRICK
Applicants: HUI DAVID Y, TSO PATRICK, UNIV CINCINNATI, HUI, DAVID, Y., TSO, PATRICK, UNIVERSITY OF CINCINNATI
Application year: 1999
Main classification: C07K14
IPC codes: A61K38, C07K14