Volume Two – The Back, the second release in the revolutionary DVD series for at-home, physician-guided physical therapy from BodyWorksMD™ is now available. Following the success of the first DVD in the series, Volume One – The Knee, Volume Two – The Back features simple and effective injury prevention and rehabilitation techniques for the back developed by Dr. Mark Klion and Dr. James Capozzi, both instructors at the Mount Sinai School of Medicine in New York City.

The DVD helps patients recover from their injuries by showing a variety of routines and advice demonstrated by Dr. Klion who is a board-certified orthopaedic surgeon as well as an accomplished marathon and triathlon competitor. Together with colleague Dr. James Capozzi, Dr. Klion developed the series in order to help people with their physical therapy who would otherwise not have the time for a traditional rehabilitation program.

BodyWorksMD™ Volume Two – The Back DVD teaches the specific exercises that are required for the chosen level of therapy. As the back’s condition improves, the program allows viewers to progress to higher levels of stretching and strengthening exercises. BodyWorksMD™ guides the viewer through many of the same routines used by physical therapists in traditional rehab programs.

“As with our initial DVD, The Back offers a truly revolutionary concept in that it helps people whose busy schedules don’t allow them to attend the typical treatment sessions,” remarked Dr. Klion. “Instead of patients having to travel to receive physical therapy, we are bringing physical therapy directly into a patient’s home.”

The concept of “No Pain, No Gain” does not apply to the BodyworksMD™ DVD series but rather, it helps patients understand the injury and help to begin the process of healing. BodyWorksMD™ Volume Two – The Back is a 30 minute, physician-guided rehabilitation program that will increase flexibility and strength in the back. The program is designed for use 3 to 4 times per week in the convenience of a person’s own home or on-the-go.

The BodyWorksMD™ series was developed by board-certified orthopaedic surgeons Dr. Mark Klion and Dr. James Capozzi, instructors at the Mount Sinai School of Medicine in New York City, in collaboration with certified physical therapist Paul Larosa. BodyWorksMD™ also includes a bonus section on spine anatomy and the treatment of common back injuries featuring former pro-triathlete and top international coach, Troy Jacobson. Volume Two – The Back is now available online at www.bodyworksMD.com.

The BodyWorksMD™ series plans a full range of DVDs designed to provide a physical rehabilitation program for common orthopaedic and sports related injuries. Coming soon, future titles in the series will include Volume Three – The Shoulder. Dr. Mark Klion hosts the series, leading viewers through easy-to-follow exercise routines that can be done in the comfort of one’s own home or on-the-go.

Volume Three – The Shoulder Now Available in Groundbreaking BodyWorksMD™ Physician-Guided DVD Series for PT

Volume Three – The Shoulder, the third release in the revolutionary DVD series for at-home, physician-guided physical therapy from BodyWorksMD™ is now available. Following the success of the first two DVDs released in the series, entitled Volume One – The Knee and Volume Two – The Back, The Shoulder features simple and effective injury prevention and rehabilitation techniques for the shoulder developed by Dr. Mark Klion and Dr. James Capozzi, both instructors at the Mount Sinai School of Medicine in New York City.

The DVD helps patients recover from their injuries by showing a variety of routines and advice demonstrated by Dr. Klion who is a board-certified orthopaedic surgeon as well as an accomplished marathon and triathlon competitor. Together with colleague Dr. James Capozzi, Dr. Klion developed the series in order to help people with their physical therapy who would otherwise not have the time for a traditional rehabilitation program.

BodyWorksMD™ Volume Three – The Shoulder begins with the Self-Assessment section to determine the level of therapy required. Next, in the Techniques section, the DVD teaches the specific exercises that are required for the chosen level of therapy. The Main Program is a 20 minute follow-along session instructed by Dr. Mark Klion. As the shoulder’s condition improves, the program allows viewers to progress to higher levels of stretching and exercise. BodyWorksMD™ guides the viewer through many of the same routines used by physical therapists in traditional rehab programs.

“As with our first two DVDs, The Shoulder offers a truly revolutionary concept in that it helps people whose busy schedules don’t allow them to attend the typical treatment sessions,” remarked Dr. Klion. “Instead of patients having to travel to receive physical therapy, we are bringing physical therapy directly into a patient’s home.”

The concept of “No Pain, No Gain” does not apply to the BodyworksMD™ DVD series but rather, it helps patients to understand the injury and help to begin the process of healing. BodyWorksMD™ Volume Three – The Shoulder features a 20 minute, physician-guided rehabilitation program that will increase flexibility and strength in the shoulder. The program is designed for use 3 to 4 times per week in the convenience of a person’s own home or on-the-go.

The BodyWorksMD™ series was developed by board-certified orthopaedic surgeons, Dr. Mark Klion and Dr. James Capozzi, instructors at the Mount Sinai School of Medicine in New York City, in collaboration with certified physical therapist Paul Larosa. BodyWorksMD™ also includes a bonus section on shoulder anatomy and the treatment of common shoulder injuries featuring former pro-triathlete and top international coach, Troy Jacobson. Volume Three – The Shoulder is now available online at www.BodyWorksMD.com.

The BodyWorksMD™ series plans a full range of DVDs designed to provide a physical rehabilitation program for common orthopaedic and sports related injuries. Dr. Mark Klion hosts the series, leading viewers through easy-to-follow exercise routines that can be done in the comfort of one’s own home or on-the-go.

A New Approach in OA: Dietary Management

Page 1 of 2 ISS. 0905 #10203

Figure 1

Recent News and Trends

With the recalls of selective COX-2 inhibitors and FDA’s recommendation to place a “black box” warning on the labels of

most Rx and OTC anti-inflammatory drugs, physicians are changing their prescribing habits due to heightened safety risks. 1

Many physicians have returned to prescribing older NSAIDs, including OTC products, even with their gastrointestinal side

effects. Some physicians have even stopped prescribing drugs for OA altogether. Patients are finding more information on

osteoarthritis (OA) from the media, often unbalanced or sometimes untrue, and many have chosen self-management without

much regard for potential side effects. Originally, OA was thought of as a degenerative disease associated with joint injury

and aging. However, recent insights have shown that after initial damage, OA progresses due to an excess of arachidonic

acid (AA) metabolism that increases inflammatory responses. Thus, OA is a metabolic deficiency disease which responds to

dietary management.

The Problem: Balancing Fatty Acid Metabolism to Manage Disease

While drugs focus on treating or masking symptoms, OA patients need help to manage the metabolic processes of OA,

thereby normalizing the levels of key metabolites. The initial event in the development of OA is damage to joints through

traumatic injury or overuse and release of phospholipids from damaged cell membranes which are converted to arachidonic

acid (AA) by phospholipase A2, a necessary fatty acid building block for membranes in the body. Metabolism of AA also

generates necessary fatty acid molecules for platelet aggregation, maintenance of stomach mucosa, organ function, proper

blood flow, urine production, blood pressure, tissue repair, and viral immunity.2-3 AA is metabolized via the COX

[cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2)] and LOX [5-lipoxygenase (5-LOX)] pathways into

thromboxanes, prostaglandins, prostacyclins, and leukotrienes (Figure 1)4. In addition, AA is converted via an oxidative

mechanism into F2-isoprostane, malondialdehyde, and 4-hydroxynonenal molecules, which directly degrade cartilage and

induce other inflammatory proteins.5 As aging occurs, however, AA both from the diet and the conversion of phospholipids

accumulates in excess in the body. The metabolism of excess AA to the above metabolites and its associated cyclical

inflammation is what propagates the disease and leads to cartilage degradation over time.6 In this metabolic sense,

inflammation is not merely a symptom of OA, rather this

inflammation cascade is the essence of the disease itself.

Managing the AA metabolic processes can ultimately

ease functional stiffness and inflammation, and restore

functional mobility.

The balance of AA metabolites is very important to

avoid deleterious effects on normal functions in the

body. As an example, two of the most important AA

metabolites for maintenance of normal kidney and

cardiovascular function are thromboxanes and

prostacyclins.7 Thromboxanes, produced by platelets via

the COX-1 enzyme, are involved in proper platelet

aggregation and also cause vasoconstriction in the

vasculature. Prostacyclins, generated from AA via COX-

2, are required for vasodilation of vessels and are

antagonistic to thromboxanes.8 If the production of

prostacyclins is selectively inhibited to a high level, then

thromboxanes dominate by constricting arteries and

arterioles causing decreases in urine perfusion in the

kidney and blood flow in the microvasculature around

the heart. Decrease in urine perfusion leads to increased

systolic blood pressure and peripheral edema, while

decreased blood flow to the heart can starve the tissue of oxygen and nutrients, especially if a person has plaque

accumulation. Both of these events lead to stress on the cardiovascular system, which contribute to increased incidence of

heart attack and stroke. These products of enzymatic AA conversion must remain balanced to allow the body to function

properly.9

A New Approach: Dual COX/LOX Mechanism of Action

A new approach on the market for OA is through dual COX/LOX mechanism of action (a.k.a. dual inhibition).10 This

approach helps to restore the balance of fatty acids, by damping AA metabolism non-selectively across the COX and LOX

A New Approach in OA: Dietary Management

Page 2 of 2 ISS. 0905 #10203

pathways, thereby minimizing common side effects. This balanced down-regulation, though weaker than traditional NSAIDs

and selective COX-2 inhibitor drugs, allows the body to produce AA metabolites at relatively equal levels to maintain

function within the body. Dual inhibitors may provide an answer for the imbalances that traditional NSAIDs (COX-1

imbalance) and selective COX-2 inhibitors (COX-2 imbalance) cause in AA metabolism. A prescription product utilizing

this new approach is a medical food product called Limbrel™. Medical foods are an FDA regulated class of foods meant to

provide distinctive nutrition requirements or to restore metabolic balances, and in this case, the balance between COX-1 and

COX-2 activity. Limbrel has been gaining wide acceptance based on its safety and ability to manage the metabolic processes

of OA using food-based ingredients. It contains concentrated levels of food-based ingredients called flavonoids which also

act as a potent antioxidant to limit oxidative conversion of AA to other damaging fatty acid products affecting cartilage

degradation. Licofelone from Merkle of Germany is currently the only prescription drug dual inhibitor in phase III trials,

and is not expected to be approved and marketed for a number of years. Its safety profile per published studies shows fewer

gastrointestinal events than NSAIDs and selective COX-2 inhibitors.10 Judging from the current spate of patents by major

pharmaceutical companies, we can expect to see more dual inhibitors as either drugs or medical foods in the future for the

treatment or dietary management of OA.

Medical Foods

FDA regulates “Medical Foods” as a discrete class of medical products for the dietary management of diseases or medical

conditions, when a nutritional or metabolic imbalance characterizing the disease or condition can be restored with nutrients,

specially formulated in an oral administration taken under a physician’s supervision. Therefore, medical foods are different

from drugs, because they work on the underling metabolic process of a disease or condition, instead of merely masking or

modifying its symptoms. The governing definition of medical foods is listed in Section 5(b) of the Orphan Drug Act (21

U.S.C. 360ee(b)(3)) which states that a medical food is “a food which is formulated to be consumed or administered

enterally [or orally] under the supervision of a physician and which is intended for the specific dietary management of a

disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established

by medical evaluation.”Medical foods are safe because one of their other statutory requirements is that their ingredients

have GRAS (Generally Recognized As Safe) status (see below). Medical foods have been distributed in hospitals as special

nutritional formulations containing vitamins, trace elements, minerals, fatty acids, flavonoids and amino acids for diabetes

mellitus, renal disease, pernicious anemia, gastrointestinal disorders, cachexia, chronic pancreatitis, elevated homocysteine,

etc. Medical foods are manufactured according to FDA cGMP (current Good Manufacturing Practices). FDA actively

enforces compliance with its medical foods regulations and performs regular inspections of medical foods manufacturing

facilities. Unlike dietary supplements which are intended for healthy populations, medical foods are intended to meet the

specific nutritional needs of a diseased patient population. Medical foods require physician supervision, and are required to

be distributed by prescription in many states prior to reimbursement.

GRAS (Generally Recognized As Safe)

GRAS is a strict safety standard set forth by the FDA, requiring technical demonstration of non-toxicity and safety, as well

as a general recognition and agreement by experts that the ingredients are safe for public consumption. Many ingredients

have been determined by the FDA to be GRAS, and are listed as such by regulation, in Volume 21 Code of Federal

Regulations (CFR) Sections 182, 184, and 186. Other ingredients may achieve self-affirmed GRAS status via a panel of

independent experts in the pertinent field who co-author a GRAS Report. Finally, a few ingredients have been specifically

permitted by FDA as safe medical foods ingredients, e.g., Folic acid, in Volume 21 CFR Section 172.345(f). Some experts

believe achieving GRAS status is an even higher standard of safety than the standard applied to drug products where a given

compound is considered safe for a particular indication in a particular patient population at a particular dose for a specified

duration of use, after a risk/benefit analysis. Dietary supplements, OTC drugs and prescription drugs are not required to

have GRAS ingredients. Limbrel contains GRAS ingredients that have been safely consumed by widespread populations

around the world.

1 http://www.fda.gov/cder/drug/infopage/COX2/default.htm (Accessed on July 19, 2005)

2 Goetzl EJ, An S, Smith WL. 1995. Specfficity of expression and effects of eicosanoid mediators m normal physiology and human diseases. FASEB J. 9:1051-1058

3 The Eicosanoids, Ed. Curtis-Prior P, John Wiley & Sons, New York, NY, 2004

4 Felson et al. 2000. Osteoarthritis: New Insights: Part 1: The Disease and Its Risk Factors. Ann Intern Med. 133(8): 635-46

5 Esterbauer, H, Schaur, RJ, Zollner, H. 1991. Chemistry and biochemistry of 4-hydroxynonenal, malondialdehyde, and related aldehydes. Free Rad. Biol. Med. 11:81–128;

Roberts, LJ, Morrow, JD. 1997. The generation and actions of isoprostanes. Biochim. Biophys. Acta, 1345:121–135.

6 McAlindon, T, Felson, DT. 1997. Nutrition: risk of osteoarthritis. Annal Rheum Dis, 56:397-402.

7 Bunting, S, Moncada, S, Vane, JR. 1983. The prostacyclin—thromboxane A2 balance: pathophysiological and theraputic implications. Br. Med. Bull. 39:271-6.

8 Solomon DH. 2005. Selective cyclooxygenase 2 inhibitors and cardiovascular events. Arthritis Rheum. 2005 Jul;52(7):1968-78.

9 Bing, RJ, Lomnicka, M. 2002. Why do cyclo-oxygenase-2 inhibitors cause cardiovascular events? J. Am Coll Cardiol. 39:421.

10 Martel-Pelletier, J, Lajeunesse, D, Reboul, P, Pelletier, JP. 2003. Therapeutic Role of Dual Inhibitors of 5-LOX and COX, Selective and Non-Selective Non-Steroidal Anti-

Inflammatory Drugs. Ann. Rhem. Dis, 62:501-09.

More detailed product information available at www.limbrel.com ISS.0905 #10005

Limbrel™ Product Profile

Distributed by Prescription #68040-601-16

“Safety That Works in Osteoarthritis”

Product Background

• Usage – For the safe, daily clinical dietary management of the metabolic processes of osteoarthritis (OA).

• Ingredients – Flavocoxid is a blend of primarily flavonoids, baicalin & catechin (from phytochemical food sources)

which are manufactured under prescription drug cGPM standards.

• Administration – Take one 250 mg capsule every 12 hours. This may be increased to two or more 250 mg

capsules every 12 hours under a physician’s supervision. Safe to be taken with or without other foods.

• FDA Regulated Product Class – Medical Food (not a drug or dietary supplement).

• Distribution – National distribution by prescription through retail pharmacies. National wholesaler order numbers:

(1) Amerisource 4774204; (2) Bergen 982722; (3) Cardinal 3568052; (4) McKesson 1256866.

• Promotion – Only via education and detailing to medical professionals (260+ detailing reps to MD/DO/PA/NP’s).

• Category – Arthritis affects 1 in 3 Americans and is the #1 cause of disability. Arthritis costs the U.S. economy

$82.5 billion annually, including over $6 billion in prescription product costs and growing at >10% annually with

aging population. Many products have had considerable cardiovascular and gastrointestinal safety concerns.

Product Benefits

• Safety – Across a range of critical parameters, Limbrel has been proven safe:

o Ingredients have GRAS (Generally Recognized As Safe) status; GRAS is the strict FDA safety standard

applied to food ingredients which designates “safe for public consumption”.

o In clinical studies, side effects were comparable to placebo.

o In safety and toxicology studies (animal & in-vitro), serological/hematological/histological measures are

comparable to placebo.

o In post marketing surveillance (n=16,452), side effects reported have been <0.25%. Predominant side effects

are: transient upper body rash (mild allergic reaction), indigestion, and synovitis.

• Effectiveness – Limbrel manages the distinctive nutritional requirements of OA by restoring the homeostasis of

OA metabolic processes in primarily two ways:

o Through inhibition of arachidonic acid (AA) metabolism down the 5-LOX (lipoxygenase) pathway, in addition to balanced inhibition across the COX-1 and COX-2 (cyclooxygenase) pathways. Limbrel is not a selective

COX-2 inhibitor. Limbrel is the first product with metabolic activity on both COX & LOX pathways.

o By acting as a powerful antioxidant to soak up reactive oxygen species (ROS) which convert AA to oxidative

products such as isoprostanes that directly degrade cartilage.

• Clinical & Scientific Support – Limbrel and its ingredients are supported by numerous medical and scientific

studies including:

Results of a Randomized, Double Blind, Placebo Controlled Study

Measure Limbrel Marketed Rx Control Placebo p-value

Functional Stiffness -41.5% -16.3% -2.3% p=0.001

Functional Mobility +34.3% +3.4% -6.8% p=0.002

Reimbursement Status

• Coverage – Presently, most U.S. healthcare plans and PBM’s reimburse Limbrel on a Tier-3 co-pay ($25-50 per

prescription). These include Aetna, United, Humana, Cigna (with prior authorization), Wellpoint and most Blue

Cross Blue Shield plans. Individual plans may vary.

• Cost Savings – Limbrel offers opportunities for lowering the cost of OA care in multiple ways:

o Daily Product Cost: Limbrel is on average 30% less expensive than leading branded Rx products.

o Total Cost of Care: Limbrel’s relatively low incidence of side effects can result in fewer complications such as

bleeding ulcers & cardiovascular events, which require additional costly drugs & hospitalization.

o Rebates: Attractive rebates to managed care organizations and buying groups are available.

Product Information

LIMBREL™

flavocoxid (U.S. patents pending) capsules by oral

administration

A specially formulated medical food product, consisting

primarily of a proprietary blend of flavonoid (polyphenol)

ingredients, for the clinical dietary management of the

metabolic processes of osteoarthritis (OA).Must be

administered under physician supervision.

OSTEOARTHRITIS (OA)

OA as a Metabolic Deficiency Disease*

Metabolic processes are important in the progression of OA.

After initial damage to the joint due to trauma, overuse of the

joint, or genetic factors, a cascade of inflammation triggered

by the release of cytokines (e.g., TNFα, IL-β, IL-6) begins the

development of OA. These cytokines up-regulate the

increased expression of COX-2 (cyclooxygenase-2) and 5-

LOX (5-lipoxygenase) enzymes, which metabolize fatty acids

in the joint. This process is both enzymatic as well as

oxidative, and occurs at a cellular level, where the essential

fatty acid, arachidonic acid (AA), is converted into various

inflammatory products.

With age, elevated levels of AA accumulate both from the diet,

and from the increased conversion of phospholipids produced

by further damage to cells in the joint. Though the initial

damage that causes OA is mainly due to overuse, injury, or

genetics, the cartilage degradation which occurs over time is

characterized by the chronic, heightened metabolism of this

accumulated AA to excess inflammatory metabolites.

Therefore, OA is sustained by imbalanced AA metabolism.

Managing AA metabolism benefits OA patients by decreasing

the damaging, metabolic inflammatory processes in the joint to

improve functional mobility, reduce stiffness, and decrease

joint discomfort.

When joint damage occurs, released phospholipids from

damaged cell membranes are converted to AA. Metabolism of

AA then generates fatty acid metabolites that serve the body

in other capacities for platelet aggregation, maintenance of

stomach mucosa, organ function, proper blood flow, urine

production, blood pressure, viral immunity, bone turnover and

tissue repair. AA is metabolized via the COX (COX-1 & COX-

2) and LOX (5-LOX) pathways to thromboxanes,

prostaglandins, prostacyclins, and leukotrienes. The balance

of AA metabolism by COX-1 and COX-2 is essential for critical

regulators of renal and cardiovascular function, thromboxanes

(vasoconstrictors) and prostacyclins (vasodilators). An

imbalance of these metabolites can result in high blood

pressure, peripheral edema, and in severe cases, myocardial

infarction. AA, metabolized by 5-LOX, generates strong

chemoattractant molecules, leukotrienes (particularly LTB4),

which cause the migration of white blood cells (WBCs) to the

site of injury. After damage to the cartilage, there is an influx

of WBCs attracted to the joint which release histamines,

produce reactive oxygen species (ROS) and cytokines, and

degranulate triggering additional inflammatory processes not

treated by traditional non-steroidal anti-inflammatory drugs

(NSAIDs) or selective COX-2 inhibitors. In fact, treatment with

these products has been shown to shunt AA metabolism down

the 5-LOX pathway thereby increasing, rather than reducing,

inflammation in cartilage. In addition, AA is converted via an

oxidative mechanism mediated by ROS to F2-isoprostane,

malondialdehyde, and 4-hydroxynonenal, oxidized lipids which

directly degrade cartilage and induce other inflammatory

proteins.

*References available upon request.

DESCRIPTION

Primary Ingredients

LIMBREL (flavocoxid) consists of a proprietary blend of two

types of flavonoids, Free-B-Ring flavonoids and flavans, from

Scutellaria baicalensis and Acacia catechu. These ingredients

in LIMBREL are Generally Recognized As Safe (GRAS). The

standard for an ingredient to achieve GRAS status requires

not only technical demonstration of non-toxicity and safety, but

also general recognition of safety through widespread usage

and agreement of that safety by experts in the field. Many

ingredients have been determined by the U.S. Food and Drug

Administration (FDA) to be GRAS, and are listed as such by

regulation, in Volume 21 Code of Federal Regulations (CFR)

Sections 182, 184, and 186. Other ingredients may achieve

“self-affirmed” GRAS status via a panel of experts in the

pertinent field who co-author a GRAS Report. Finally, a few

ingredients have been specifically permitted by FDA as safe

medical foods ingredients, e.g., Folic acid, in Volume 21 CFR

Section 172.345(f).

Flavonoids

Flavonoids are a group of phytochemical compounds found in

all vascular plants including fruits and vegetables. They are a

part of a larger class of compounds known as polyphenols.

Many of the therapeutic or health benefits of colored fruits and

vegetables, red wine, and green tea are directly related to

their flavonoid content.

The specially formulated flavonoids found in LIMBREL or their

related compounds (i.e., other flavonoids, salicylates,

anthocyanins) cannot be obtained from conventional foods at

the same level in the normal American diet. This quantity of

daily flavonoid intake generally would need to be significantly

greater for patients with hypochlorihidira or low intrinsic factor,

both of which occur most often in the elderly population. OA

may not be managed by a mere change to the normal diet due

to the sheer volume of vegetable and fruit matter that would

need to be consumed.

Baicalin

The primary Free-B-Ring flavonoid is baicalin (5,6,7-

trihydroxyflavone,7-O-β-D-glucuronopyranoside) derived from

the phytochemical food source material Scutellaria baicalensis

with a molecular weight of 446.37. Its molecular formula is

C21H18O11, with the following chemical structure:

Baicalin

Catechin

The primary flavan is composed of catechin (3,3’,4’,5,7-

pentahydroxyflavan (2R,3S form)), and its stereo-isomer,

epicatechin (3,3’,4’,5,7-pentahydroxyflavan (2R,3R form))

from the phytochemical food source material Acacia catechu

with a molecular weight of 290.27. Its molecular formula is

C15H14O6, with the following chemical structure:

Catechin

Other Ingredients

LIMBREL contains the following “inactive” or other ingredients,

as fillers, excipients, and colorings: magnesium stearate,

microcrystalline cellulose, Maltodextrin NF, gelatin (as the

capsule material), FD&C Blue #1, and FD&C Green #3.

Capsules do not contain fructose, glucose, sucrose, lactose,

gluten or flavors.

Medical Food

Medical food products are often used in hospitals (e.g., for

burn victims or kidney dialysis patients) and outside of a

hospital setting under a physician’s care (e.g., for PKU, AIDS

patients, cardiovascular disease, osteoporosis) for the dietary

management of diseases in patients with particular medical or

metabolic needs due to their disease or condition. Congress

defined “medical food” in the Orphan Drug Act and

Amendments of 1988 as “a food which is formulated to be

consumed or administered enterally [or orally] under the

supervision of a physician and which is intended for the

specific dietary management of a disease or condition for

which distinctive nutritional requirements, based on

recognized scientific principles, are established by medical

evaluation.” LIMBREL has been developed, manufactured,

and labeled in accordance with both the statutory and the FDA

regulatory definition of a medical food. LIMBREL is to be used

under a physician’s supervision.

Physical Description

LIMBREL is a yellow to light brown powder. It is partially

soluble in water and glycerol, soluble in ethanol, methanol,

and acetonitrile. It is practically insoluble in hexane. Each

capsule of LIMBREL contains 250 mg of flavocoxid, as noted

in the Primary Ingredients Section.

CLINICAL PHARMACOLOGY

Mechanism of Action

LIMBREL acts by restoring and maintaining the balance of

fatty acids in OA. LIMBREL dampens AA metabolism at

relatively equal levels in the COX pathway (mediated by

conversion of AA via the COX-1 & COX-2 enzymes) as well as

inhibiting the metabolism of AA by the 5-LOX enzyme. This

balanced inhibition of metabolism in the COX pathway yields

relatively equal levels of thromboxanes, prostaglandins, and

prostacyclins which are key mediators of systemic organ

function. Inhibition of these mediators in the COX pathway in

conjunction with inhibition of leukotrienes in the LOX pathways

results in a “dual inhibition” mechanism which dampens

inflammation without affecting organ function. This balanced

down-regulation of these enzymatic pathways is relatively

weak when compared to the effects of traditional NSAIDs and

selective COX-2 inhibitors while allowing the body to produce

AA metabolites at relatively equal levels to maintain function

within the body and avoid serious side effects. LIMBREL is not

selective for either COX-1 or COX-2 enzymes. Inhibition of 5-

LOX has been shown in cell-based assays to reduce the

production of LTB4, an agent that fosters WBC chemotaxis

and the subsequent release of histamines, ROS, and proinflammatory

cytokines. Direct inhibition of the 5-LOX enzyme

has been observed as well in enzymatic assays.

LIMBREL also acts as a strong antioxidant to limit the

oxidative conversion of AA by ROS to other damaging fatty

acid products. LIMBREL acts as an antioxidant to neutralize

such ROS species as hydroxyl radical, superoxide anion

radical and hydrogen peroxide. LIMBREL has demonstrated

an oxygen radical absorbance capacity (ORAC) of 5,517

µmolTE/g, as compared to Vitamin E (1,100 µmolTE/g) andVitamin C (5,000 µmolTE/g).

Through the actions of these mechanisms, LIMBREL is

beneficial for the specific dietary management of the metabolic

aspects of osteoarthritis. Clearly, inflammation and joint

discomfort are the clinical manifestations of OA. At a

biochemical and metabolic level, inflammation is not merely a

symptom or a manifestation of the disease. Chronic

inflammation with elevated metabolic production of

inflammatory metabolites sustains and causes the progression

of OA. Thus, successful dietary management of the metabolic

processes of OA, results in a reduction of its characteristic

inflammation by correcting OA’s distinctive imbalance in AA

metabolism.

Hepatic, Renal, and Gastrointestinal Histology

LIMBREL’s effect on hepatic, renal, gastric, and

duodenal tissue histology was tested in four animal toxicity

studies; two for acute use and two for sub chronic use.

In the acute use studies, two test groups, healthy juvenile

male and female mice, each consumed a 2,000 mg per

kilogram dose (10,000 mg per day human equivalent, or 20

times the recommended human use of 500 mg per day) daily

for 14 days. In two different sub chronic use studies, three test

groups of healthy adult male and female mice consumed 50

mg, 250 mg and 500 mg per kilogram doses (250 mg, 1,250

mg and 2,500 mg per day human equivalent, or .5, 2.5, and 5

times the recommended human use of 500 mg per day) for 28

and 91 days respectively.

In all studies, the test subjects were evaluated relative to

placebo control groups of healthy subjects with similar ages

and sexes. Observations across all groups revealed no organ

nor behavioral abnormalities, nor differences in weight gain.

Neither study showed changes in hepatic, renal, gastric, or

duodenal histology. Blood electrolytes were unchanged, and

liver enzyme levels and markers of renal function were all

within normal limits.

Food Effects

LIMBREL is safe taken with or without other foods. Taking

LIMBREL one hour before or after meals may help to increase

the absorption of LIMBREL’s key ingredients. This observation

is based upon a pharmacokinetic study in humans, as well as

in-market clinical experience in analyzing physician and

patient product reports. Food does not affect the metabolism

of LIMBREL and may buffer effects of slight indigestion.

Metabolism

LIMBREL is primarily absorbed by albumin in the blood and

only a minor amount (<10%) metabolized via glucuronidation

and sulfation by hepatic metabolism involving cytochrome

P450 isoenzymes (CYP). A primary ingredient constituent,

baicalin, undergoes hydrolysis of the glucuronide moiety in the

upper intestinve via the action of intestinal flora and is

absorbed as the aglycone, baicalein. Glucuronidation and

sulfation of baicalein occurs intrahepatically.In vitro CYP

assays using a microsomal enzyme system, CYP inhibition is

nominal, ranging from 11% inhibition to 23% inhibition of

selected isozymes when studied at a 10 micromolar

concentration.

Drug Interactions

In vitro studies indicated that LIMBREL is not a significant

inhibitor of cytochrome P450 1A2, 2C9, 2C19, 2D6, or 3A4.

These isoenzymes are principally responsible for 95% of all

detoxification of drugs, with CYP3A4 being responsible for

detoxification of roughly 50% of drugs. Based on the results of

this assay test, LIMBREL does not appear to have a

pronounced effect on drug metabolizing enzymes.

LIMBREL was tested at a 10µM concentration in human

recombinant (sf9 cells) using spectrophotometric quantization

of 7-benzyloxy-4-(trifluoromethyl)-coumarin as substrate. In

this test model, if inhibition does not reach at least 50% at 10

µM, CYP inhibition is considered to be insignificant and no

further development of titration curves is deemed necessary.

LIMBREL, therefore, does not appear to have a pronounced

effect on the inhibition of hepatic drug metabolizing enzymes

based on this 10µM concentration. The data for CYP

inhibition is shown below:

Table 1

Cytochrome P450 Assay

CYP

Isoenzyme

Reference

Compound

Test Article %

Inhibition

(Mean of 2

Replicates)

1A2 Furafylline 23%

2C9 Sulfaphenazole 11%

2C19 Tranylcypromine 16%

2D6 Quinidine 15%

3A4 Ketoconazole 11%

CLINICAL EXPERIENCE

LIMBREL has demonstrated significant functional

improvements when used for the clinical dietary management

of the metabolic processes of OA. LIMBREL was evaluated in

a randomized, double blind, placebo-controlled clinical trial of

90 days duration that enrolled 60 patients. Subjects were sexmatched

and recruited from ages 40 to 75 years with an

average age of 55-57 years per arm. Subjects taking NSAIDS

engaged in a two-week washout period before beginning the

trial. Patient activity was not restricted, and patients were free

to withdraw from the trial at any time for any reason. There

were only a minimal number of dropouts.

In patients with OA, use of LIMBREL at 125 mg and 250 mg

each twice daily by oral administration, resulted in significant

improvements in WOMAC (Western Ontario and McMaster

Universities Osteoarthritis Index) functional endpoints of

stiffness and mobility over those scores of placebo users (See

Lingard et al. (2001) J. Bone & Joint Surg. 83:1856-1864;

Soderman and Malchau (2000) Acta Orthop. Scand. 71(1):39-

46 for an explanation of WOMAC). In this study, patients using

LIMBREL 250 mg twice daily experienced greater

improvements in functional stiffness and functional mobility at

60 and 90 days than did patients using 125 mg twice daily.

See Tables 2 and 3 below for a comparison of LIMBREL

results to placebo for each noted measure.

Table 2

90-day Functional Stiffness WOMAC Scores

Test

product

Mean %

Change* P Value Conclusion

LIMBREL

250 mg/day

-32.0% p=0.003 Significant

improvement

LIMBREL

500 mg/day

-41.4% p=0.001 Significant

improvement

Placebo -2.3% p=0.899 No significant

improvement

* Negative values represent a reduction or improvement in

functional stiffness.

Table 3

90-day Functional Mobility WOMAC Scores

Test

product

Mean %

Change* P Value Conclusion

LIMBREL

250 mg/day

+28.0% p=0.018 Significant

improvement

LIMBREL

500 mg/day

+34.3% p=0.002 Significant

improvement

Placebo -6.8% p=0.499 No significant

improvement

* Positive values represent an increase or improvement in

functional mobility.

The clinical results of the blinded study shown above have

been corroborated in an open label human trial with a mean

duration of use of 6.5 months. This trial consisted of 24

subjects: 13 males and 11 females ranging from 26 to 60

years of age. The primary endpoints were differences in

WOMAC functional mobility (65% improvement; p=0.002) and

functional stiffness (62% improvement; p=.001) scores before

vs. after taking flavocoxid.

ADVERSE REACTIONS

In a controlled clinical trial of 90 days duration, the incidence

of side effects for LIMBREL was comparable to placebo.

Some of the adverse events reported appear to have been

due to pre-existing conditions. Table 4 below lists all adverse

events except the occult events discussed below, regardless

of causality, that were reported in > 2% of patients

participating in this controlled clinical trial. Also in this study, a

small number of patients using LIMBREL and placebo

products were found to test positive for fecal occult blood.

However, the limited incidence of these adverse events was

statistically the same between the LIMBREL and placebo legs

of this trial. Patients experiencing these events were found to

have a previous history of gastrointestinal ulceration upon

retrospective analysis. To confirm the isolated nature of these

findings, two fecal occult blood studies were performed and all

patients tested negative as described in the Special

Studies/Gastrointestinal Section below.

Table 4

Adverse Events with Incidence > 2%

LIMBREL

125mg BID

LIMBREL

250mg BID Placebo

Varicose veins

(increase)

Psoriasis Gastrointestinal

upset

Hypertension

(elevation)

Fluid accumulation in

the knee

Special Studies

Gastrointestinal

In a retrospective study, 8 healthy adult subjects ranging in

age from 41 to 60 years, ingested LIMBREL daily for periods

ranging from 5 to 11 months (mean 7 months). Daily amount

ranged from 300 mg to 1500 mg (mean of 825 mg). Six

subjects were male and 2 were female. No subjects reported

a prior history of gastrointestinal ulceration. Analysis for fecal

occult blood was conducted on three consecutive days. No

subjects in this trial were positive for fecal occult blood.

In a second retrospective study, 13 healthy adult subjects

ranging in age from 38 to 58 ingested LIMBREL daily for

periods ranging from 5 to 15 months (mean of 8 months).

Daily administration ranged from 150 mg to 600 mg (mean of

375 mg). Seven subjects were male and 6 subjects were

female. No subjects reported a prior history of gastrointestinal

illness. Analysis for fecal occult blood was conducted on three

consecutive days. No subjects in this trial were positive for

fecal occult blood. One subject had an event of occult

bleeding prior to the measurement date, withdrew from the

product, and was unavailable for retrospective analysis. This

subject was found to have an unreported prior history of

gastrointestinal ulceration.

Endoscopic examinations have not been conducted in

LIMBREL users.

Special Populations

There have not been clinical studies performed in specific

pediatric, geriatric, race, hepatic insufficiency, renal

insufficiency, and immunological insufficiency patient

populations.

LIMBREL has been studied in an overweight/obese patient

population. In a randomized, double-blind placebo-controlled

safety study, 29 subjects ingested LIMBREL one 125 mg BID,

and 39 subjects ingested a placebo for 60 days. Subjects had

blood drawn both prior to and following ingestion of LIMBREL.

In this study, there were no significant differences between

LIMBREL and placebo groups in the changes between

baseline and study completion for any of the following

analytes observed in blood collection: Albumin, AG Ratio, Alk

Phos, ALK (SGPT), AST (SGOT), Basophils, Baso ABS,

Total Bilirubin, Bun/creatinine ratio, Calcium, Carb Dioxide,

Cardio Cap, Chloride, Total Cholesterol/HDL Cholesterol

Ratio, Total Cholesterol, Creatinine, Eosinophil, Eosinophil

ABS, Globulin, Glucose, HDL Cholesterol, Hematocrit,

Hemoglobin, LDL Cholesterol, Lymphocytes, Lymphocytes

ABS, MCH, MCHC, MCV, Monocyte, Monocyte ABS, Neutphil,

Neut ABS, Plat CNT, Potassium, Total Protein, RDW,

Red Cells, Sodium, Triglycerides, TSH, Urea (Bun) and White

Blood Cells (WBCs).

Post-Marketing Surveillance

Table 5 below lists the side effects reported by patients and

physicians in the post-marketing surveillance, as accumulated

through the date of print. Reported cases of rash and itching

may have been associated with allergies to LIMBREL’s

flavonoid ingredients, were transient in nature, and occurred

most often on the upper torso. One of the reported cases of

heart palpitation occurred in a patient with a history of heart

palpitation.

Table 5

Post-Marketing Surveillance

LIMBREL 250 mg BID

(n=23,470) Incidence %

Incidence

Skin

Rash, itching 3 0.013%

Hives 1 0.004%

Central Nervous System

Light-headedness 1 0.004%

Gastrointestinal

Diarrhea 1 0.004%

Flatulence 1 0.004%

Dyspepsia, heartburn 0 0.000%

Nausea and/or vomiting 3 0.013%

Fluid Retention

Edema 2 0.009%

Body as a Whole

Fever 2 0.009%

Hot flashes 1 0.004%

Flu Like Symptoms, NFS 1 0.004%

Cardiovascular

Recurring Heart Palpitation 2 0.009%

Musculo-skeletal

Joint Pain 2 0.004%

Synovitis 3 0.013%

Total 23 0.10%

RECOMMENDED USE

Recommended Use

LIMBREL is intended for the clinical dietary management of

the metabolic processes of osteoarthritis (OA).

Disclaimed Use

LIMBREL has not been investigated for use in the clinical

dietary management of rheumatoid arthritis (RA), acute pain

or primary dysmenorrhea.

PRECAUTIONS AND CONTRAINDICATIONS

General

LIMBREL is contraindicated in an extremely small number of

patients with hypersensitivity to any component of flavocoxid

or to flavonoids. Foods rich in flavonoid contents include:

colored fruits and vegetables, dark chocolate, tea (especially

green tea), red wine, and Brazil nuts.

Gastrointestinal (GI) Effects

LIMBREL is expected to be safe on the stomach because of

its mechanism of action. COX-1 inhibition causes the upregulation

of 5-LOX in the stomach, which converts AA to

leukotrienes (particularly LTB4). LTB4 attracts WBCs to the

stomach mucosa, which cause and expand ulcerations. There

are no specific controlled clinical trials examining LIMBREL’s

effect on the stomach in non-ulcer or ulcer patients. In an

open label study of 24 patients taking an average of

approximately 500 mg per day for a mean of 6.5 months, there

was one observation of positive fecal occult blood in a patient

with a history of hemorrhoids. Clinical experience by

physicians has shown LIMBREL to be well tolerated in

patients with a history of mild ulceration. Post-marketing

surveillance has also shown that there has not been a single

reported case of ulceration (see the Adverse Reactions

Section for patient and physician reported gastrointestinal

events associated with the use of LIMBREL).

Pediatric/Pregnancy and Lactation

There are no formal studies with LIMBREL among patients

under the age of 18 years of age or among pregnant or

lactating patients. Since there are no formal studies among

pregnant or lactating patients, as a precaution, LIMBREL is

not recommended for pregnant or lactating patients.

Over Usage

There are no known cases of LIMBREL over usage. Animal

studies have shown that consuming the equivalent of up to 20

times the recommended human usage (500 mg/day) did not

produce adverse events. However, as in most over usage

situations, symptoms following an over usage of LIMBREL

could vary according to the patient. If an over usage were to

occur, patients should be managed by systematic and

supportive care as soon as possible following product

consumption.

Physician Supervision

LIMBREL is a medical food product distributed by

prescription and must be used under physician

supervision.

PRODUCT ADMINISTRATION

Recommended Administration

For the clinical dietary management of the metabolic

processes of OA, take one 250 mg capsule every 12 hours for

500 mg total daily consumption. This may be increased to two

or more 250 mg capsules every 12 hours under a physician’s

supervision. If patients forget to take the prescribed amount,

take it as soon as they remember and then resume the normal

schedule as directed by a physician.

How Supplied

LIMBREL is supplied in 250 mg and 500 mg capsules.

LIMBREL 250 mg capsules are in two-part turquoise green

capsules with a smooth surface imprinted “LIMBREL” on one

end and “52001” on the other end, supplied as:

# Number Size

68040-601-16 Bottle of 60 capsules (250 mg)

68040-601-18 Carton of 120 capsule (250 mg) packets

containing 20 packs containing 6-capsule

packets each as a sample package (Not

For Resale)

68040-601-12 Carton of 20 capsule (250 mg) packets

containing 1 capsule each as a sample

package (Not For Resale)

68040-601-13 Carton of 20 capsule (250 mg) blister cards

containing 2 capsules each as a sample

package (Not For Resale)

68040-601-02 Blister Card of 2 capsules (250 mg) as a

sample (Not For Resale)

68040-601-01 Packet of 1 capsule (250 mg) as a sample

(Not For Resale)

LIMBREL 500 mg capsules are in two-part turquoise green

capsules with a smooth surface imprinted with two white

stripes on the cap, and imprinted “LIMBREL” and “52002” on

the body, supplied as:

# Number Size

68040-602-16 Bottle of 60 capsules (500 mg)

Store at room temperature, 59-86oF (15-30oC) [see USP

Controlled Room Temperature]. Protect from light and

moisture. LIMBREL is supplied to pharmacies in a recyclable

plastic bottle with a child-resistant cap. Dispense in a lightresistant

container as defined in the USP/NF with a childresistant

closure.

Distributed by prescription.

U.S. patents pending

www.limbrel.com

Distributed by: Manufactured by:

Primus Pharmaceuticals, Inc. PharmaFab®

Scottsdale, AZ 85251 Grand Prairie, TX 75050

PIN001361 ISS. 0206

Copyright © 2006 Primus Pharmaceuticals, Inc. All rights

reserved.

SAFE PRESCRIPTION OSTEOARTHRITIS PRODUCTINTRODUCED NATIONALLY Limbrel™ Represents New Approach for More Than 20 Million AmericansScottsdale, AZ – February 15, 2006 – Limbrel, the first prescription product developed to safely meet the nutritional requirements of patients with osteoarthritis (OA), is being introduced nationally by Primus Pharmaceuticals, Inc. OA is the most common form of arthritis, and currently afflicts more than 20 million Americans. Physicians have been prescribing traditional NSAIDs and COX-2 inhibitors for patients, but ongoing revelations about possible serious side effects associated with these drugs over the last 18 months have left many patients and physicians with increasing safety concerns.     Limbrel represents an entirely new approach to managing OA with a breakthrough in patient safety. It is regulated as a medical food, which means it has been developed to meet the specific nutritional needs of patients with OA and can only be taken under the supervision of a physician. Additionally, its ingredients meet the strict regulatory safety standard of Generally Recognized as Safe (GRAS). The standard for an ingredient to achieve GRAS status requires not only technical demonstration of non-toxicity and safety, but also general recognition and agreement on that safety by experts in the field. In addition, GRAS safety status is supported by widespread consumption of key ingredients by millions of people over generations of time.

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 “After more than eight years in development and one year in limited markets, Limbrel represents a safe and totally new approach for millions of OA patients,” said Bruce Burnett, PhD, Director of Medical Education and Scientific Affairs for Primus Pharmaceuticals, and former instructor at Yale University School of Medicine. “Because Limbrel’s ingredients are not synthetic or artificial, and they balance the body’s natural metabolic processes related to osteoarthritis, it is reassuring to physicians who have become alarmed at the serious side effects uncovered in past OA prescription drug products.”Dr. Brian J. Cole*, orthopedic surgeon, Associate Professor and Section Head of the Cartilage Restoration Center at Rush University Medical Center in Chicago, commented, “With the COX-2 product recalls, both doctors and their patients are searching for something truly safe. I am glad Limbrel is now available to orthopedists nationwide because we need something effective that addresses the concerns of our patients. The bottom line is: Limbrel works when appropriately recommended and I have had no serious side effects compared to other prescription products.  Its regulatory classification as a medical food is also reassuring to patients.” Dr. Anthony K. Hedley*, world renowned total joint surgeon and former faculty member of UCLA’s Medical School, commented about Limbrel, “The product is so effective that I prescribe it to my patients and use it myself. It’s unique for me to experience something good at the same time as my patients do.”OA is more than a degenerative disease. OA is also a metabolic disease which results from changes in certain natural processes usually triggered by injury or by wear and tear associated with the aging process. This leads to the breakdown and degradation of cartilage in the joints. The process is worsened by deficiencies in certain nutrients such as selected flavonoids, antioxidants and essential fatty acids, which help to regulate the inflammatory process. The deficiencies of these nutrients mean that certain inflammation and oxidation pathways are not functioning normally. The end results are discomfort, stiffness, and loss of movement for OA sufferers.                                           In both clinical studies and daily prescription usage under a doctor’s care, Limbrel has consistently demonstrated significant improvements in the validated OA measures of discomfort, stiffness and mobility. Limbrel contains flavocoxid, a patent-

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 pending blend of natural ingredients, comprised primarily of the concentrated flavonoids baicalin and catechin, which are recognized for their anti-inflammatory and antioxidant properties. Flavonoids are healthful ingredients found in colored vegetables, fruits, cocoa, red wine and green tea, and have been studied extensively for a wide variety of health benefits. Limbrel delivers antioxidant benefit in a highly concentrated form, which cannot be achieved simply by changing one’s normal diet. As the only marketed prescription product with COX & LOX Dual Inhibition action balancing COX-1/COX-2 (cyclo-oxygenase) metabolism and inhibiting the 5-LOX (lipoxygenase) inflammatory pathway, Limbrel directly addresses the dietary imbalances of OA rather than merely focusing on the symptoms of disease. The side effects of Limbrel have been found to be similar to placebo in clinical studies with only slightly more minor side effects of nausea and diarrhea. There has been no serious adverse event reported to-date in actual in-market usage of Limbrel by over 23,000 OA patients. For more information on Limbrel, please visit www.limbrel.com.  About Primus Pharmaceuticals, Inc.          Primus is the first specialty pharmaceutical company to focus on prescription metabolic products dedicated to improving patient quality of life without compromising safety. Primus develops branded prescription drugs and medical foods that are patented and effective in chronic or recurring diseases. The Company’s unique approach is to develop first-line medical food products formulated to restore metabolic processes at the disease source rather than focusing on symptoms. Primus promotes to targeted physician audiences and extends its sales reach and clinical capabilities through strategic partnerships. Primus is privately held and based in Scottsdale, AZ. www.primusrx.com About Limbrel™Limbrel is the first prescription product developed and formulated specifically to safely meet the distinctive nutritional requirements of patients with OA. Limbrel contains flavocoxid, a proprietary blend of natural flavonoid ingredients from food sources that meet the regulatory safety standard of generally recognized as safe (GRAS).

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Flavonoids are healthful ingredients found in colored vegetables, fruits, cocoa, red wine and green tea.  Limbrel works by restoring the body’s normal metabolic inflammatory processes through the dual inhibition (COX + LOX) of excess arachidonic acid metabolization and antioxidant action. Clinical studies have shown Limbrel to be effective in the dietary management of OA. Limbrel is manufactured according to current Good Manufacturing Practices (cGMP) for prescription drugs, even though only food cGMP is required. Itis available by prescription only, as Federal regulations require that Limbrel be used only under a physician’s supervision.  www.limbrel.com# # #* Doctors Cole and Hedley are medical advisors to Primus Pharmaceuticals, Inc.

LIMBREL™ INTRODUCED IN 500 MILLIGRAM CAPSULES NewOffering Addresses Rising Demand forSafeOsteoarthritis Prescription Product Scottsdale, AZ – August 3, 2006 – Primus Pharmaceuticals, Inc. has announced that Limbrel™, the first prescription product developed to safely meet the distinctive nutritional requirements of patients with osteoarthritis, will be offered at an increased level of 500 milligrams (mg). This latest development comes as a result of a growing demand for the medical food after the national introduction of its standard 250 mg capsule form.  A number of physicians that had begun prescribing Limbrel have found that some patients require a higher strength based on the severity of their osteoarthritis, body mass and individual differences in metabolizing concentrated flavonoid ingredients. Both Limbrel 250 mg and 500 mg capsules are prescribed to be taken twice daily, or as directed by a physician.          “We are extremely pleased that Limbrel has been so strongly embraced by doctors and patients throughout the country,” said Dr. Bruce Burnett, PhD, Director of Medical Education and Scientific Affairs for Primus Pharmaceuticals, and former instructor at Yale University School of Medicine. “Offering Limbrel at this higher prescription size provides physicians with latitude in managing the more severe cases of osteoarthritis, and helps patients who might require an increased potency for other reasons.” Nationally introduced this year, Limbrel represents an entirely new approach to managing osteoarthritis with a breakthrough in patient safety. It is regulated by the FDA as a medical food, which means it has been developed to meet the specific nutritional needs of patients with osteoarthritis, and can only be taken under the supervision of a physician. Additionally, all of its

ingredients must meet the strict FDA safety standard of Generally Recognized as Safe (GRAS). The standard for an ingredient to achieve GRAS status requires not only technical demonstration of non-toxicity and safety, but also general recognition and agreement on that safety by experts in the field. For Limbrel, GRAS status is supported by widespread consumption of its key ingredients by millions of people over generations of time.For more information on Limbrel, please visit www.limbrel.com.  About Primus Pharmaceuticals, Inc.          Primus is the first specialty pharmaceutical company to focus on prescription metabolic products dedicated to improving patient quality of life without compromising safety. Primus develops branded prescription drugs and medical foods that are patented and effective in chronic or recurring diseases. The Company’s unique approach is to develop first-line medical food products formulated to restore metabolic processes at the disease source rather than focusing on symptoms. Primus promotes to targeted physician audiences and extends its sales reach and clinical capabilities through strategic partnerships. Primus is privately held and based in Scottsdale, AZ. www.primusrx.com. About Limbrel™Limbrel is the first prescription product developed and formulated specifically to safely meet the distinctive nutritional requirements of patients with osteoarthritis. Limbrel contains flavocoxid, a proprietary blend of natural flavonoid ingredients from food sources that meet the regulatory safety standard of generally recognized as safe (GRAS). Flavanoids are healthful ingredients found in colored vegetables, fruits, cocoa, red wine and green tea. Limbrel restores the body’s normal metabolic inflammatory processes through dietary management that ultimately results in dual inhibition (COX + LOX) of excess arachidonic acid metabolization as well as antioxidant action. Clinical studies have shown Limbrel to be effective in the dietary management of osteoarthritis. Limbrel is manufactured according to current Good Manufacturing Practices (cGMPs) for prescription drugs, even though only food cGMPs are required. It is available by prescription only, as Federal regulations require that Limbrel be used only under a physician’s supervision. www.limbrel.com.  # # #