A Natural, Botanical Anti-Inflammatory 5-LOX & COX-2 Selective Inhibitor
Question: How doses Vaxamine compare to the prescription COX-2 inhibitors (Vioxx
and Celebrex) and the OTC NSAID pain relievers such as aspirin and ibuprofen?
Answer: In-vivo human oral dosing studies conducted with the active ingredient in Vaxamine™
demonstrated excellent potency and selectivity for COX-2. Oral dosing of Vaxamine™
(1 gram) produced
a 56% reduction in COX-2 versus a 62% reduction for a 400 mg. (two tablets) dose of the OTC pain
reliever Ibuprofen. However, the selectivity of Vaxamine™,
which is calculated as the COX-1 IC-50/
COX-2 IC-50, was 0.25 versus 1.41 for Ibuprofen. Therefore, Vaxamine™
is of equivalent potency to
Ibuprofen, but much more selective for the COX-2 form of the enzyme than COX-1. Based on numerous
clinical studies done with COX-2 selective inhibitors, a COX-2 selective inhibitor is expected to be gentler
on the stomach than a non-selective COX inhibitor such as Aspirin or Ibuprofen.
The prescription COX-2 inhibitor Celebrex produced a 45% reduction in COX-2 activity in our human oral
dosing study, versus 56% for Vaxamine™
, making Vaxamine™
more potent than Celebrex. The
selectivity of Celebrex (COX-1/COX-2) was 0.45 versus 1.41 for Vaxamine™
, making Vaxamine™
only more potent than Celebrex, but also more selective for COX-2 inhibition.
Vioxx, the second COX-2 inhibitor to be approved by the FDA, and also a blockbuster drug, which
achieved over $3 billion in sales, is highly selective for COX-2. Published human oral dosing studies with
Vioxx demonstrated that Vioxx produced an almost complete inhibition of COX-2, with no inhibition of
COX-1. The COX-2 selectivity for Vioxx is therefore almost 1:100, in other words, Vioxx virtually shuts
down COX-2, blocking all down stream production of prostaglandins. It is known that some prostaglandins
such as prostacyclin (PGI-2) are important for cardiovascular health, whereas pro-inflammatory
prostaglandins, such as PGE-2, are responsible for inflammation.
The natural anti-inflammatory patent pending ingredient in Vaxamine™
, derived from botanical alpha
acids, is therefore believed to be an effective pain reliever with equivalent potency (efficacy) to synthetic
drugs, but with a stomach friendly side-effect profile, especially when used on a chronic basis. Individuals,
who suffer from chronic pain such as osteoarthritis, are driven to consume pain relievers on a daily basis
due to the chronic nature of the inflammation. Chronic use of dual inhibitors of both COX-1 and COX-2
will produce gastric erosion. Conversely, too much selectivity and potency for COX-2 may result in other
side effects, such as potentially harmful cardiovascular events associated with the complete inhibition of
prostaglandin production. By producing about a 56% reduction in COX-2, Vaxamine™ does not completely shut down the
production of all prostaglandins, but does inhibit the production of pro-inflammatory PGE-2 enough to
provide pain relief equivalent to OTCs and prescription pain relievers, but with better selectivity for
COX-2. By inhibiting COX-1 by about 10-15%, Vaxamine™ provides for some anti-platelet aggregation,
while also preserving prostacyclin production, which is beneficial for cardiovascular health.
™ "The Gastro and Cardio friendly all-natural anti-inflammatory"
• Preserves prostacyclin production
• Anti-platelet aggregation via slight COX-1 inhibition
• Stomach friendly due to good COX-2 selectivity Vaxamine™
™ Human Oral Dosing/In-Vivo Studies
Two human oral dosing clinical studies have been conducted with the COX-2 inhibitor in Vaxamine™
. These studies were designed to assess the COX-2 and COX-1 inhibition of Vaxamine™
in vivo. The two most important things that need to be determined when screening
for new COX-2 inhibitor anti-inflammatory compounds are the potency and selectivity. The
potency is determined by the magnitude of COX-2 inhibition from baseline, and the selectivity is
determined from the ratio between COX-2 and COX-1. If the COX-2 inhibition is divided by the
COX-1 inhibition, a number is obtained, and the lower the number, the more selective the
compound is for COX-2 inhibition relative to COX-1 inhibition.
Cyclooxygenase Inhibiting Activity Of Vaxamine
Oral Dosing Study In Humans
Summary of Results
This study was designed to assess the potential of Vaxamine™
, to inhibit cyclooxygenase-1 and
2, (COX-1, COX-2) compared to a control product with known COX inhibiting and pain-
relieving properties (400mg ibuprofen). The criterion for success was comparable COX inhibition
and selectivity equal to or greater than the ibuprofen control. Method
Twenty four healthy subjects were enrolled in
the study following screening for inclusion
Cox-2 inhibitory potency and selectivity
and exclusion criteria. Twelve subjects were
The effectiveness of a Cox-2 inhibitor can be expressed
in terms of its potency
, and in terms of its selectivity
ingredient in Vaxamine™
mg.).Twelve subjects were assigned to the
Cox-2 potency refers to the ability of a product to
ibuprofen control group; dosing in the control
reduce the amount of Cox-2 enzyme in the blood by a
group was a single two tablet dose (400 mg.).
given percent. For example, a product which inhibits
Blood samples were taken immediately before
Cox-2 enzyme by a maximum of 50% within a given
the dosing of test products, as well as at
sampling period is more potent than one that inhibits it
subjects in the control group gave blood
Cox-2 selectivity refers to the degree to which a product
is able to inhibit Cox-2 without inhibiting Cox-1.
immediately before dosing, and 0.5, 1, 2, and
Selectivity is calculated by dividing the integrated Cox-
by the integrated Cox-2 potency
The smaller the number below one, the greater the Cox-
Plasma from each of the blood samples were
evaluated for potency and selectivity in a
Integrated potency is potency over time: for example, if
validated ex vivo assay. It should be noted that the only way to measure COX-2 is by the
a product inhibits Cox-2 by 50% over 4 hours, the
integrated potency equals 200 (50 X 4). If the same
Pharmacol 126, 1824-30; 1999, in which the
product inhibits Cox-1 by 25% over 4 hours, its
test compounds are administered orally, blood
integrated Cox-1 potency will be 100, and its Cox-2
selectivity will be 100 divided by 200, or 0.5.
Product effects over the sampling time are expressed as a percentage of baseline Cox-1 and –2
activity in Figure 1
. The maximum Cox inhibition within the 9-hour (active products) or 3 hour
(ibuprofen control) sampling time represents each product’s Cox-2 inhibitory potency. The Cox-2
inhibitory potency of Vaxamine™ (56%) was in the range of the Cox-2 inhibitory potency of a
single 2-tablet dose of ibuprofen (62.2%). As expected from published reports1 and in previous
unpublished studies, plasma from subjects in the ibuprofen group (bottom right panel) inhibited
Cox-1 and Cox-2 by 80% and 60%, respectively. The potency and selectivity results are shown in
Integrated Cox potency and selectivity values. Means +- standard error.
Integrated Potency: Increasing number indicates increasing inhibition of Cox-1 or Cox-2. Cox-2 selectivity Ratio: the smaller the number below 1, the greater the selectivity. Selectivity comparisons within products: * = P < 0.05, ** = P < 0.01, n.s. = not significant. Selectivity comparisons between products: ratios not sharing a letter are significantly different.
showed statistically significant Cox-2 selectivity. (Ibuprofen, by contrast and as
expected, was selective towards Cox-1.) The Cox-2 selectivity of Vaxamine
™ was significantly
different (p<0.01) from that of ibuprofen.
Vaxamine™/Celecoxib Comparison Study
A comparison study was conducted to compare the effects of Vaxamine™
(Celebrex®). Six subjects were dosed with Vaxamine (1,000 mg. “Now only 150mg”) and six
subjects with Celecoxib and COX inhibition activity was measured in plasma according to the
previous protocol. Additionally, six subjects were given a 400-mg. dose of Ibuprofen for
comparison. Results of the study are summarized below.
Maximum Cox-2 reduction from baseline over 3 hours, by product, and Cox-2 specificity, by
product. Comparative data from separate Celebrex and Ibuprofen pilot study included.
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