Register Now
Why register?
Login
 The leading web portal for pharmacy resources, news, education and careers October 22, 2017
Pharmacy Choice - Pharmaceutical News - Patent Application Titled "Cardiovascular Disease Primary Prevention Agent for Patients Having High Blood Levels of High-Sensitivity C-Reactive... - October 22, 2017

Pharmacy News Article

 10/22/17 - Patent Application Titled "Cardiovascular Disease Primary Prevention Agent for Patients Having High Blood Levels of High-Sensitivity C-Reactive...

Patent Application Titled "Cardiovascular Disease Primary Prevention Agent for Patients Having High Blood Levels of High-Sensitivity C-Reactive Protein" Published Online (USPTO 20170273929)

By a News Reporter-Staff News Editor at Heart Disease Weekly According to news reporting originating from Washington, D.C., by NewsRx journalists, a patent application by the inventors KIYOHARA, Yutaka (Fukuoka-shi, JP); NINOMIYA, Toshiharu (Fukuoka-shi, JP); YANO, Takashi (Tokyo, JP), filed on June 9, 2017, was made available online on October 5, 2017 (see also Pharmaceutical Companies).

The assignee for this patent application is Mochida Pharmaceutical Co., Ltd.

Reporters obtained the following quote from the background information supplied by the inventors: "Cardiovascular diseases are diseases which are leading causes of death in advanced countries. Primary and secondary prevention of this disease is a national health issue of importance, and recently, importance of the primary prevention which prevents the disease before the onset is widely recognized.

"Cardiovascular diseases such as coronary artery diseases and cerebral stroke have common pathological background of arteriosclerosis, and risk factors of the arteriosclerosis include smoking, dyslipidemia (hyperlipidemia), hypertension, diabetes, obesity, lack of exercise, and the like. Accordingly, minimization of these risk factors is important in reducing the risk of the onset of cardiovascular diseases.

"Accumulated investigations have proven that onset and progress of the arteriosclerosis is induced by the overlapping of a plurality of risk factors. The most important risk factor is dyslipidemia.

"According to 'Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012' (Non-patent literature 1), goals are set for the patients diagnosed with dyslipidemia depending on the control division based on the risk (absolute risk) of suffering from atherosclerotic diseases (namely, coronary artery disease, cerebral stroke, and arteriosclerosis obliterans based on atherosclerosis). More specifically, the control division is set by stratification based on the presence and absence of the additional risk of diabetes, chronic kidney disease, noncardiogenic cerebral infarction, and peripheral arterial disease. According to this guideline, life style is first improved and the adaptation of pharmacotherapy is then considered in the case of the primary prevention (the case with no history of the onset of coronary artery disease), while pharmacotherapy is considered together with the improvement of the life style in the case of the secondary prevention (the case with the history of the onset of the coronary artery disease).

"Most typical therapeutic agents for dyslipidemia (in particular, high low density lipoprotein (hereinafter also referred to as 'LDL') cholesterolemia) used for pharmacotherapy are statin drugs (inhibitors for hydroxymethylglutaryl-CoA (hereinafter also referred to as 'HMG-CoA') reductase). The statin drugs which emerged in late 1980's are now sold in more than a hundred countries, and these drugs are said to be administered to at least 30 million people per day. Non-patent literature 1 describes that use of statin drug is recommended for high LDL cholesterolemia, and administration of eicosapentaenoic acid (hereinafter also referred to as 'EPA') is considered in the case of dyslipidemia with high risk of cardiovascular disease as in the case of complication with diabetes or hypertension. The EPA preparation contains high purity ethyl eicosapentaenoate ester (hereinafter also referred to as 'EPA-E') which has been extracted, for example, from sardine oil, esterified, and purified as an effective component, and it has the action of reducing blood neutral fat as well as the action of inhibiting intravascular thrombus formation through suppression of the aggregatory action of the platelet.

"Patent Literature 1 describes a composition for preventing recurrence of cardiovascular events containing the EPA-E as an effective component which is useful for the prevention of the recurrence (secondary prevention) of the cardiovascular event, and in particular, which is expected to have a preventive effect for the cardiovascular event that recurs despite the therapy using the HMG-CoA reductase inhibitor and the recurrence of cardiovascular event that takes place after the passage of the unstable period after the cardiovascular reconstruction in the hyperlipidemia patient.

"Patent Literature 2 describes a composition for preventing recurrence of cerebral stroke containing the EPA-E as an effective component which is useful in preventing the recurrence (secondary prevention) of the cerebral stroke, and more particularly, which is expected to have a preventive effect for the cerebral stroke that recurs despite the therapy using the HMG-CoA reductase inhibitor and the recurrence of cerebral stroke that takes place after 6 month or more after the onset of the cerebral stroke in the hyperlipidemia patient.

"Non-Patent Literature 2 describes that, in the evaluation of the prevention of incipiency (primary prevention) of coronary artery disease for about 5 years, 18% decrease was found for the group of hypercholesterolemia patients having the EPA-E and the statin drug administered, although this result was not significant in terms of the risk compared to the group of patients with single administration of the statin drug.

"However, it was not clear whether the EPA preparation was effective as an agent for primary prevention of cardiovascular disease irrespective of the suffering from dyslipidemia and/or the administration of the HMG-CoA reductase inhibitor preparation. Test items and reference values for the administration were also unclear.

"In the meanwhile, Non-Patent Literature 3 discloses that ratio of the concentration of EPA to the concentration of arachidonic acid (hereinafter also referred to as 'AA') in the plasma total lipid (hereinafter also referred to as 'EPA/AA ratio') is expected for its use as a new bio-marker for the risk of cardiovascular death based on the results of an epidemiologic study. Non-Patent Literature 4 describes that the value of serum high sensitivity C reactive protein (hereinafter also referred to as 'hs-CRP') is expected for its use as a new bio-marker for the risk of the onset of the cardiovascular disease also based on the results of an epidemiologic study. However, it has been unclear whether appropriate evaluation for the risk of the cardiovascular disease, and in particular, the risk of incipiency (hereinafter also referred to as 'primary risk') of the cardiovascular disease is possible."

In addition to obtaining background information on this patent application, NewsRx editors also obtained the inventors' summary information for this patent application: "Technical Problems

"An object of the present invention is to provide an agent for primary prevention of cardiovascular disease, a marker for evaluating primary risk of cardiovascular disease, a method for extracting the subject with high risk of cardiovascular disease, and/or a method for primary prevention of cardiovascular disease.

"Solution To Problems

"In order to achieve the object as described above, the inventors of the present invention carried out an intensive study, and found in the epidemiologic study examining the association of the serum EPA/AA ratio with primary risk of cardiovascular disease in the group with no history of cardiovascular disease, while there is no association between the serum EPA/AA ratio and the primary risk of cardiovascular disease in the group with a serum hs-CRP value of less than 1.0 mg/L, in the group a the serum hs-CRP value of at least 1.0 mg/L, the primary risk of cardiovascular disease increases with the decrease in the serum EPA/AA ratio, and namely, there is a significant difference between the group with a serum hs-CRP value of less than 1.0 mg/L and the group with a serum hs-CRP value of at least 1.0 mg/L; and that in the group with a serum hs-CRP value of at least 1.0 mg/L, the primary risk of cardiovascular disease significantly increases at the serum EPA/AA ratio of less than 0.50. The inventors of the present invention also found that, in the subjects with no history of cardiovascular disease with a serum hs-CRP value of at least 1.0 mg/L, administration of the EPA-E results in the decrease of the onset risk of cardiovascular disease, and such effect is found irrespective of the administration of the statin drug. In other words, it has been found that the risk of new onset of cardiovascular disease can be reduced by the EPA-E administration in the subject having a serum hs-CRP value of at least 1.0 mg/L irrespective of whether the patient has dyslipidemia or not, for example, whether the value of the blood LDL cholesterol is within the therapeutic range. The present invention has been completed on the bases of such findings, and more specifically, the present invention is as described below.

"(1) An agent for primary prevention of cardiovascular disease which is administered to a subject with no history of cardiovascular disease having a serum or plasma hs-CRP value (hereinafter also referred to as 'blood hs-CRP value' or 'hs-CRP value') of at least 1.0 mg/L for reducing risk of cardiovascular disease, wherein the agent comprises at least one member selected from the group consisting of EPA, its salts, and its esters as an effective component.

"(2) The agent for primary prevention of cardiovascular disease according to the above (1), wherein the subject has an EPA/AA ratio in the total lipid of serum or plasma (hereinafter also referred to as 'serum EPA/AA ratio' or 'EPA/AA ratio') of less than 0.50.

"(3) The agent for primary prevention of cardiovascular disease according to the above (2), wherein the serum EPA/AA ratio is less than 0.25.

"(4) The agent for primary prevention of cardiovascular disease according to any one of the above (1) to (3) wherein the agent is administered to the subject and effective irrespective of whether the subject suffers from dyslipidemia.

"(5) The agent for primary prevention of cardiovascular disease according to the above (4), wherein the dyslipidemia is high LDL cholesterolemia.

"(6) The agent for primary prevention of cardiovascular disease according to any one of the above (1) to (5), wherein the agent is administered to the subject and effective irrespective of whether the subject is being administered with HMG-CoA reductase inhibitor.

"(7) The agent for primary prevention of cardiovascular disease according to any one of the above (1) to (6), wherein the at least one member selected from the group consisting of EPA, its salts, and its esters is EPA-E.

"(8) The agent for primary prevention of cardiovascular disease according to any one of the above (1) to (7) further comprising at least one member selected from the group consisting of docosahexaenoic acid (hereinafter also referred to as 'DHA'), its salts, and its esters.

"(9) The agent for primary prevention of cardiovascular disease according to the above (8), wherein the at least one member selected from the group consisting of DHA, its salts, and its esters is ethyl docosahexaenoate ester (hereinafter also referred to as 'DHA-E').

"(10) The agent for primary prevention of cardiovascular disease according to any one of the above (1) to (9), wherein the cardiovascular disease is coronary artery disease or cerebral stroke.

"(11) The agent for primary prevention of cardiovascular disease according to the above (10), wherein the cardiovascular disease is myocardial infarction or angina.

"(12) The agent for primary prevention of cardiovascular disease according to the above (10), wherein the cerebral stroke is cerebral infarction or cerebral hemorrhage.

"(13) A combined marker for evaluating primary risk of cardiovascular disease of a subject who has no history of cardiovascular disease, wherein the marker comprises a blood hs-CRP value and a serum EPA/AA ratio.

"(14) The combined marker according to the above (13), wherein the risk of cardiovascular disease is evaluated to be high when the hs-CRP value is at least 1.0 mg/L and the EPA/AA ratio is less than 0.50.

"(15) The combined marker according to the above (13), wherein the risk of cardiovascular disease is evaluated to be ultra-high when the hs-CRP value is at least 1.0 mg/L and the EPA/AA ratio is less than 0.25, and the risk of cardiovascular disease is evaluated to be high when the hs-CRP value is at least 1.0 mg/L and the EPA/AA ratio is at least 0.25 and less than 0.50.

"(16) The combined marker according to any one of the above (13) to (15), wherein the cardiovascular disease is coronary artery disease or cerebral stroke.

"(17) The combined marker according to the above (16), wherein the cardiovascular disease is myocardial infarction or angina.

"(18) The combined marker according to the above (16), wherein the cerebral stroke is cerebral infarction or cerebral hemorrhage.

"(19) A method for extracting a subject with high risk of cardiovascular disease, comprising the steps of:

"measuring a blood hs-CRP value of a subject;

"measuring a serum EPA/AA ratio of the subject; and

"extracting a subject with high risk of cardiovascular disease by combining the blood hs-CRP value and the serum EPA/AA ratio.

"(20) A method for extracting a subject with high risk of cardiovascular disease, including the steps of measuring a blood hs-CRP value of a subject and measuring a serum EPA/AA ratio of the subject,

"the method comprising the step of:

"extracting a subject with high risk of cardiovascular disease by combining the blood hs-CRP value and the serum EPA/AA ratio.

"(21) The method for extracting a subject with high risk of cardiovascular disease according to the above (19) or (20), wherein the subject having the hs-CRP value of at least 1.0 mg/L and the EPA/AA ratio of less than 0.50 is extracted as a high risk subject of cardiovascular disease.

"(22) The method for extracting a subject with high risk of cardiovascular disease according to the above (19) or (20), wherein the subject having the hs-CRP value of at least 1.0 mg/L and the EPA/AA ratio of less than 0.25 is extracted as a high risk subject of cardiovascular disease, and a subject having the hs-CRP value of at least 1.0 mg/L and the EPA/AA ratio of at least 0.25 and less than 0.50 is extracted as a high risk subject of cardiovascular disease.

"(23) The method according to any one of the above (19) to (21), wherein the subject has no history of cardiovascular disease.

"(24) An assay kit for use in the method of any one of the above (19) to (23) including at least means for measuring a blood hs-CRP value.

"(25) A method for primary prevention of cardiovascular disease comprising the step of administering the agent for primary prevention of cardiovascular disease of any one of the above (1) to (12) to the subject extracted by the method of the above (23).

"Advantageous Effects of Invention

"The present invention provides a marker for evaluating the primary risk of cardiovascular disease; a method for extracting a subject with high risk of cardiovascular disease; an agent for primary prevention of cardiovascular disease comprising at least one member selected from the group consisting of EPA, its salts, and its esters as an effective component which is administered to subjects having no history of cardiovascular disease with a blood hs-CRP value of at least 1.0 mg/L to thereby reduce the risk of cardiovascular disease; and/or a method for primary prevention of cardiovascular disease.

"The agent for primary prevention of cardiovascular disease of the present invention can be administered to both the patient receiving the statin drug and the patient not receiving the statin drug, and it can reduce the risk of cardiovascular disease in the subject having no history of cardiovascular disease with a blood hs-CRP value of at least 1.0 mg/L.

"The agent for primary prevention of cardiovascular disease of the present invention can be administered to both patients suffering from dyslipidemia (hyperlipidemia) and subjects who have never been diagnosed with the dyslipidemia (hyperlipidemia), irrespective of the type and seriousness of the dyslipidemia and irrespective of whether the subject is receiving a statin drug, to thereby reduce the risk of cardiovascular disease in the subjects with no history of cardiovascular disease with a blood hs-CRP value of at least 1.0 mg/L.

"The marker for evaluating the risk of cardiovascular disease of the present invention is capable of evaluating the risk of cardiovascular disease at a high precision and objectively by using the blood hs-CRP value and the serum EPA/AA ratio.

"When the marker for evaluating primary risk of cardiovascular disease of the present invention is used, subjects with high primary risk of cardiovascular disease requiring the administration of the agent for primary prevention of cardiovascular disease of the present invention can be extracted.

"By using the method for primary prevention of cardiovascular disease of the present invention, the primary prevention of cardiovascular disease can be accomplished for the subject with no history of cardiovascular disease but having high primary risk of cardiovascular disease with a blood he-CRP value of at least 1.0 mg/L, irrespective of whether the subject has dyslipidemia (hyperlipidemia), irrespective of the type and seriousness of the dyslipidemia, and irrespective whether the subject is receiving the administration of a statin drug. The method for primary prevention of cardiovascular disease of the present invention is also a method effective for detecting subjects with high risk of cardiovascular disease at an early stage to thereby reduce the risk of cardiovascular disease in the subjects who are already receiving a statin drug and experiencing some therapeutic effects for the dyslipidemia."

For more information, see this patent application: KIYOHARA, Yutaka; NINOMIYA, Toshiharu; YANO, Takashi. Cardiovascular Disease Primary Prevention Agent for Patients Having High Blood Levels of High-Sensitivity C-Reactive Protein. Filed June 9, 2017 and posted October 5, 2017. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220170273929%22.PGNR.&OS=DN/20170273929&RS=DN/20170273929

Keywords for this news article include: Pharmaceutical Companies, Stroke, Albumins, Diabetes, Angiology, Reductase, Cardiology, Hemorrhage, Immunology, Proteomics, Epidemiology, Heart Attack, Hypertension, Dyslipidemias, Heart Disease, Brain Ischemia, Hyperlipidemia, Immunoproteins, Atherosclerosis, LDL Cholesterol, Pharmacotherapy, Arteriosclerosis.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2017, NewsRx LLC



(c) 2017 NewsRx LLC

Pharmacy News Index
  Drug Delivery Systems
  Drugstores
  FDA Final Approvals
  Front Page Healthcare News
  Generic Drugs
  Hospital Industry
  Internet Pharmacy
  IT in Healthcare
  Medicare & Medicaid
  Over-the-Counter Drugs
  Pharm Industry Trends and Policy
  Pharmaceutical Development
  Pharmaceutical Industry

LIVE ONLINE CE

Last Chance
Oct 23: Vitamin D Primer for Pharmacy Professionals
Oct 24: Metabolic Syndrome: The Heart of Any Wellness Practice
Oct 25: Dispensing Controlled Substances in Today’s Pharmacy
Oct 26: Management of Schizophrenia & Acute Agitation
Oct 27: Influenza 2017-2018: An Update on Prevention and Treatment
Click for entire Webinar Calendar

Special Announcement

Free Membership
Enjoy Drug Search, industry newsletters and more...

Nursing Jobs
Are you a nurse looking for a job?

Check out the Nursing Job Source.

Your number one choice for nursing jobs.



Websites » RxCareerCenter.comRxSchool.comClubStaffing.comNursingJobSource.comRN.com
Copyright © 2017 Pharmacy Choice - All rights reserved.
Terms and Conditions | Privacy Statement
888-682-4415