Title: Method for the treatment of symptoms related to normal hormonal variations in women
United States Patent: 6,569,471
Issued: May 27, 2003
Inventors: Winther; Kaj (Copenhagen, DK); Hedman; Christer (Molnlycke, SE); Karnerud; Lars (Tenhult, SE)
Assignee: Natumin Pharma AB (Huskvarna, SE)
Appl. No.: 942967
Filed: August 31, 2001
Abstract
A method for the treatment of symptoms related to normal hormonal variations in women during fertile, peri- and post-menopausal age, by the administering of a composition comprising, as active ingredients, a water and/or fat-soluble cytosolic extract of pollen, optionally combined with Royal Jelly and Vitamin E.
DETAILED DESCRIPTION OF THE INVENTION
The active composition in the invention is a new remedy with the aim to
be beneficial for the treatment of symptoms related to variations in the
normal sex hormone pattern, such as the above mentioned. It is a combination
of natural health products and comprises
a cytosolic pollen-pistil extract (PI 82),
a cytosolic pollen grain extract (GC FEM), and optionally
Royal Jelly, a substance produced by worker honey bees,
Vitamin E
Further, common drug processing compounds may be included such as diluents,
glidants, lubricants, disintegrants, flavoring and coloring agents well
known to the man skilled in the art of pharmaceutical sciences. The active
ingredients can be included in formulations of any form, such as tablets,
powders, granules, and tinctures or included in foodstuff of different
origin, e.g. as functional food.
PI 82 is a cytosolic pollen-pistil extract rich in superoxide dismutase
(SOD) mimics. The source of PI 82 is freshly harvested pollen grains and
pistils. The pollen and pistils are allowed to react under very specific
conditions. Substances obtained in this reaction are SOD mimics, flavanoids,
tannins and polyphenols. In vitro studies have shown that the extract has
high superoxide dismutase activity and prevents the formation of free
radicals Experiences from double blind patient investigation show that PI 82
protects the body from free radicals and their negative influence on the
body. Furthermore PI 82 improves the red cell function, thus improving
oxygen perfusion to different tissues.
GC FEM is another water-soluble cytosolic extract from pollen. The cytoplasm
content of the pollen contains in addition to the above-mentioned substances
high amount of carbohydrates and protein. Amongst the proteins carotenoids
and flavanoids are found. It also contains traces of estrogen substances.
The PI82 and GC FEM extracts are selected and harvested primarily from
Poaceae. The extracts are treated to achieve germinal openings of the pollen
as well as to minimize risk for allergic pollen reactions.
Royal Jelly is produced by the salivary glands of the worker honeybees from
various plant materials. It contains a rich source of e.g. pantothenic acid,
which has been called an anti-stress vitamin. It is preferably included in
the composition in lyophilized form.
Test of the Effects on Symptoms Relating to Normal Variations of the Sex
Hormone Pattern of Women of Fertile Age
A double-blind study was performed to investigate the efficacy and
tolerability of the active composition in comparison to placebo in
outpatients suffering from symptoms relating to normal variations in the sex
hormone pattern of women. Patients with depression and anxiety were
excluded.
The trial was performed on 29 women aged 27 to 54 years (mean 39.4 years),
with regular menstrual cycles of 24 to 34 days. Criteria for admission were
women aged 20 to 54 years with regular menses complaining of symptoms
related to variations in the normal sex hormone pattern.
After a pre-study screening, half of the patients (Group A) took 2 placebo
tablets twice daily, starting on the first day after menstruation and
continued this treatment for two menstrual cycles, i.e. treatment period 1.
The other half (Group 13) followed the same regimen, but they were
administered 2 tablets twice daily each tablet comprising 120 mg PI 82, 36
mg GC FEM, 6 mg Royal Jelly and 10 mg Vitamin B. Thereafter, and without any
"wash-out" period, each group crossed over to the other medication for
another two menstrual cycles, i.e. treatment period 2. Both groups started
their medication periods at the same time. No formal rules for withdrawal,
other that the patient's own wish to withdraw, were considered necessary. No
dropouts due to protocol deviations were recorded.
Statistical Analysis
A non-parametric method (Wilcoxon signed-rank, matched pair analysis) was
used for analysis of differences between treatment scores, on an intention
to treat basis. A p-value of 0.05 or less was adopted as the acceptable
significance level. All numerical values have been reduced to 3 significant
figures. With 29 patients available for evaluation, a day-to-day variation
of 12%, a Type I error risk of 5%, and a Type II error risk of 10%, it would
be possible to detect a score difference of 16%. To detect a possible
"carry-over" effect it was decided that a separate statistical analysis of
Group A and B should also be performed (cf. Table 13 and 14). An independent
institution outside the clinic performed the statistical analysis.
Drug Formulations, Randomization and Blinding
The active composition and placebo tablets were formulated and packed to be
indistiguishable for patients as well as for doctor and nurse. Treatments
were allotted at random by computer generation for clusters of four
individuals. The code list was generated and kept outside the clinic until
the study had been completed. Drug formulations were packed and labeled for
one month's treatment, and with a code number identifying the patient.
Results
Effects were analyzed as differences in scores for placebo and treatment
with the disclosed composition, respectively.
Of the symptoms from the first test protocol, evaluated with VAS (visual
analog scale) by patients, the product significantly reduced four as
compared to placebo, viz. irritability (p<0.05), dysphoria (p<0.02), feeling
of being bloated (p<0.05), and edema (p<0.02). The reduction in scores
amounted to 39%, 36%, 41%, and 53% respectively. The reduced awareness of
edema agrees well with the 57% reduction in gain in body weight. Tendencies
of effects are also shown for mastalgia and headache. The letters "ns" below
means "not significant". A spillover effect might be obtained from the
treatment with the active compound to the placebo test. According to later
follow-up tests, reported in Table 13 and 14, remarkably good effects were
obtained.
The scope of the invention is as defied in the appended claims.
Irritability Score
During the first cycle the irritability score (visual analogue scales 1-10)
was 4.2 during placebo treatment as compared to 3.1 during treatment with
the active composition. The corresponding figures for the second cycle was
4.4 for placebo and 2.8 for the active composition. The difference between
placebo and the active composition was statistically significant between the
two treatments during the second cycle, while there was a tendency of
improvement during the first. The score was statistically significant lower
during the second the active composition period compared to the first
(p<0.05), and a carry-over effect was observed.
TABLE 1
Irritability score (VAS 0-10) during treatment with Placebo and the active
composition (n = 29) at each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 4.2 3.1 4.4 2.8
Range 0-9.4 0-9.5 0-9.3 0-9.5
S.D. 3.3 3.0 3.4 3.1
p-value ns p < 0.05
Dysphoria Score
During the first cycle the dysphoria score (visual analogue scales 1-10) was
3.1 during placebo treatment as compared to 2.6 during the active
composition treatment. The corresponding figures for the second cycle was
3.9 for placebo and 2.3 for the active composition. The difference between
placebo and the active composition was statistically significant between the
two treatments dung the second cycle, while there was a tendency of
improvement during the first.
TABLE 2
Dysphoria score (VAS 0-10) during treatment with Placebo and the active
composition (n = 29) at each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 3.1 2.6 3.9 2.3
Range 0-7.8 0-9.5 0-9.2 0-9.5
S.D. 2.7 3.1 3.1 2.9
p-value ns p < 0.02
Bloating Score
During the first cycle the bloating score (visual analogue scales 1-10) was
3.9 during placebo treatment as compared to 2.4 during the active
composition treatment. The corresponding figures for the second cycle was
3.7 for placebo and 2.2 for the active composition. The difference between
placebo and the active composition was statistically significant between the
two treatments for the first cycle and on the borderline on the second cycle
(0.054). There was a significant carry-over effect.
TABLE 3
Bloating score (VAS 0-10) during treatment with Placebo and the active
composition (n = 29) at each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 3.9 2.4 3.7 2.2
Range 0-9.5 0-9.5 0-9.5 0-9.5
S.D. 3.0 2.9 3.6 2.9
p-value p < 0.05 p = 0.054
Edema Score
During the first cycle the edema score (visual analogue scales 1-10) was 3.3
during placebo treatment as compared to 2.2 during the active composition
treatment. The corresponding figures for the second cycle was 3.2 for
placebo and 1.7 for the active composition. The difference between placebo
and the active composition was statistically significant between the two
treatments during the second cycle. A significant carry-over effect was
found.
TABLE 4
Edema score (VAS 0-10) during treatment with Placebo and the active
composition (n = 29) at each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 3.3 2.2 3.2 1.7
Range 0-10 0-9.5 0-10 0-9.5
S.D. 3.4 3.1 3.6 2.7
p-value ns p < 0.02
Mastalgia Score
During the first cycle the mastalgia score (visual analogue scales 1-10) was
3.3 during placebo treatment as compared to 2.9 during treatment with the
active composition. The corresponding figures for the second cycle was 3.5
for placebo and 2.5 for the active composition. The differences between
placebo and the active composition were not statistically significant
between the two treatments.
TABLE 5
Mastalgia score (VAS 0-10) during treatment with Placebo and the active
composition (n = 29) at each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 3.3 2.9 3.5 2.5
Range 0-10 0-10 0-10 0-8.3
S.D. 3.4 3.2 3.8 2.9
p-value ns ns
Weight Increase
During the first cycle the patients weight increase was 1.2 kg during
placebo treatment as compared to 1.0 during treatment with the active
compound. The corresponding figures for the second cycle was 1.4 for placebo
and 0.6 for the active compound. The difference between placebo and the
active compound was statistically significant between the two treatments
during the second cycle. It was a statistically significant difference
between the first the active compound period and the second. A significant
carry-over effect was found.
TABLE 6
Weight (kg) increase in connection with PMTS during treatment with
Placebo and the active compound (n = 29) at each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 1.2 1.0 1.4 0.6
Range 0-5.5 0-3 0-5 0-3
S.D. 1.3 1.0 1.3 0.8
p-value ns p < 0.01
Tension Score
During the first cycle the tension score (visual analogue scales 1-10) was
3.4 during placebo treatment as compared to 2.6 during treatment with the
active compound. The corresponding figures for the second cycle was 3.7 for
placebo and 2.5 for the active compound. The difference between placebo and
the active compound was not statistically significant between the two
treatments during any of the cycles, even if it was a strong tendency of
improvement during the second (p=0.060). There was a statistically
significant carry-over effect between the periods.
TABLE 7
Tension score (VAS 0-10) during treatment with Placebo and the active
compound (n = 29) at each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 3.4 2.6 3.7 2.5
Range 0-8.2 0-9.5 0-9.2 0-9.5
S.D. 2.7 3.2 3.0 3.0
p-value ns ns
Headache Score
During the first cycle the headache score (visual analogue scales 1-10) was
3.7 during placebo treatment as compared to 2.1 during treatment with the
active composition. The corresponding figures for the second cycle was 3.0
for placebo and 2.4 for the active composition. The differences between
placebo and the active composition were not statistically significant
between the two treatments.
TABLE 8
Headache score (VAS 0-10) during treatment with Placebo and the active
composition (n = 29) at each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 3.7 2.1 3.0 2.4
Range 0-10 0-8.9 0-9.5 0-9.5
S.D. 3.3 2.8 3.4 3.1
p-value ns ns
Sleep Disturbances Score
During the first cycle the sleep disturbances score (visual analogue scales
1-10) was 2.8 during placebo treatment as compared to 2.0 during treatment
with the active composition. The corresponding figures for the second cycle
was 3.1 for placebo and 2.5 for the active composition. The differences
between placebo and the active composition were not statistically
significant between the two treatments.
TABLE 9
Sleep disturbances score (VAS 0-10) during treatment with Placebo and
the active composition (n = 29) at each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 2.8 2.0 3.1 2.5
Range 0-10 0-8.7 0-10 0-9.3
S.D. 3.3 3.1 3.6 3.3
p-value ns ns
Safety, Heart Rate
No statistically significant differences between placebo and the active
composition were found between the two treatments.
TABLE 10
Heart rate after treatment with Placebo and the active composition
(n = 29) after each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 74.2 76.3 75.4 77.6
Range 64-90 64-94 56-88 68-92
S.D. 6.7 8.5 8.1 6.5
p-value ns ns
Systolic Blood Pressure
No statistically significant differences between placebo and the active
composition were found between the two treatments.
TABLE 11
Systolic blood pressure after treatment with Placebo and the active
composition (n = 29) after each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 114.5 114.8 112.1 113.5
Range 90-135 90-150 95-125 90-130
S.D. 12.0 13.9 8.5 10.4
p-value ns ns
Diastolic Blood Pressure
No statistically significant differences between placebo and the active
composition were found between the two treatments.
TABLE 12
Diastolic blood pressure after treatment with Placebo and the active
composition (n = 29) after each menstrual cycle.
Placebo Active Placebo Active
1st Cycle 1st Cycle 2nd Cycle 2nd Cycle
Mean 77.4 77.1 78.1 79.4
Range 60-90 60-85 70-90 70-90
S.D. 6.4 7.0 5.3 5.9
p-value ns ns
A further statistical analyze is given in Table 13. The analyze was
performed in line with the test of Wilcoxon test performed above. However,
the participants obtained placebo during the first two treatment periods and
the active composition during the two second treatment periods. The
treatment with the active composition shows an unexpected and remarkably
better effect as compared to the placebo treatment.
TABLE 13
Group A
Mentrual cycle number
1 2 3 4
Treatment
Placebo Placebo Active Femal Active Femal
Code
P value matrix
AP1 AP2 AF1 AF2 AP1 vs
AP2 AP2 vs AF1 AF1 vs AF2 AP2 vs AF2
Tension 4.1+/-2.9 4.2+/-3.3 1.7+/-2.8 1.2+/-2.4 ns
0.0134 0.0117 0.0012
Irritability 4.9+/-3.5 4.7+/-3.8 2.1+/-2.5 1.4+/-2.5 ns
0.0261 0.0020 0.0081
Dysphoria 3.2+/-2.4 4.7+/-3.1 1.6+/-2.7 1.4+/-2.3 ns
0.0107 (0.0907) 0.0024
Weight change (kg) 1.5+/-1.6 1.6+/-1.6 0.6+/-0.9 0.4+/-0.5 ns
0.0239 ns 0.0039
Edema 4.3+/-3.7 4.2+/-3.8 0.5+/-0.8 0.5+/-0.8 ns
0.0039 ns 0.0010
Swelling (bloating) 4.7+/-2.3 4.4+/-3.6 1.2+/-1.2 0.9+/-1.6 ns
0.0245 ns 0.0107
Breast tension 4.1+/-3.4 3.8+/-3.8 2.5+/-3.0 1.4+/-2.6 ns
ns 0.0195 0.0105
Headache 4.0+/-3.6 3.5+/-3.7 0.9+/-1.2 1.6+/-3.0 ns
0.0137 ns 0.0371
Sleep disturbance 4.5+/-3.6 5.0+/-3.9 2.2+/-3.1 2.6+/-3.6 ns
0.0266 ns 0.0081
Overall wellbeing 3.2+/-1.3 3.4+/-1.5 1.5+/-1.2 1.5+/-1.1 ns
0.0048 ns 0.0012
Interf. social/prof. life 3.7+/-2.7 3.7+/-3.3 1.2+/-1.6 0.8+/-1.8
ns 0.0093 (0.0781) 0.0034
TABLE 14
Group B
Mentrual cycle number
1 2 3 4
Treatment
Active Active
comp. comp. Placebo Placebo
Code P
value matrix
BF1 BF2 BP1 BP2 BF1 vs BF2 BF2
vs BP1 BP1 vs BP2 BF2 vs BF2
Tension 3.6+/-3.3 3.9+/-3.2 2.6+/-2.4 3.1+/-2.5 ns
ns ns ns
Irritability 4.3+/-3.1 4.3+/-3.2 3.5+/-2.9 4.1+/-2.9 ns
ns ns ns
Dysphoria 3.5+/-3.6 3.2+/-3.4 2.9+/-3.0 3.0+/-2.9 ns
ns ns ns
Weight change (kg) 1.4+/-1.0 0.8+/-1.0 0.8+/-0.8 1.1+/-0,9 0.0239
ns ns ns
Edema 4.1+/-3.7 2.9+/-3.4 2.4+/-2.9 2.1+/-3.0 0.0176
ns ns ns
Swelling (bloating) 3.7+/-3.4 3.6+/-3.6 3.1+/-3.1 3.1+/-3.6 ns
ns ns ns
Breast tension 3.4+/-3.4 3.6+/-3.1 2.5+/-3.3 3.3+/-4.1 ns
ns ns ns
Headache 3.4+/-3.5 3.2+/-3.1 3.4+/-3.0 2.5+/-3.2 na
ns ns ns
Sleep disturbances 1.8+/-3.5 2.4+/-3.2 1.0+/-1.7 1.0+/-1.5 ns
ns ns 0.0371
Overall wellbeing 2.8+/-1.4 2.8+/-1.4 2.6+/-1.4 2.6+/-1.4 ns
ns ns ns
Interf. social/prof. life 2.2+/-2.2 2.6+/-3.2 1.6+/-2.4 1.7+/-2.5 ns
ns ns ns
During placebo no adverse events were reported. During the first cycle of
the active composition treatment three patients noted a shortened menstrual
cycle and one patient reported dizziness. During the second cycle with the
active composition 5 patients reported a shorter menstrual cycle than
normal. Apart from these events the patients tolerated the active
composition very well. The lack of severe adverse events is also obvious
from Tables 10-12 above.
The results from these studies show that the active composition had a strong
effect on tension, irritability, dysphoria, weight gain, edema, bloating,
mastalgia, headache, sleep disturbances, overall wellbeing and interference
in the social and professional life. The active composition was well
tolerated by the patients.
It is interesting to note that the effect of the active composition was more
pronounced during the second menstrual cycle compared to the first cycle of
active treatment. This indicates that the treatment should be continued for
at least two cycles before it should be evaluated whether the product works
for the individual patient. For one of the ingredients included in the
active composition--PI 82--a similar observation has been made regarding the
effect on See radical formation. The onset of effect is seen first after a
month treatment. Another reason for this may be that the effect of the
active composition continues after having been withdrawn. The observed
carry-over effect may indicate his. This effect may be one of the reasons
why the efficacy of the active composition is not optimal during the first
cycle, i.e. it may be that the onset of efficacy for the product is faster
than the present data indicate. This is supported by the data from an open
pilot study were the effects were as good during the first menstrual cycle
as during the second.
The mode of action is with present scientific knowledge not known. As the
product contains three different natural constituents, each with a
theoretically contributing effect, the combination of these may be a reason
for the observed effect. The constituents PI 82 and GC FEM contain SOD
mimics such as flavanoids, tannin polyphenols and carotenoids. These SOD
mimics have an effect on free radical formation, which may be a factor
involved in redistribution of fluids, including edema, seen under stress
situation. An improved oxygen perfusion may also be a contributing effect.
Vitamin E is added to the composition as an active ingredient or as an
antioxidant and stabilizer for the tablet formulation.
Test of the Effects on Symptoms Relating to Normal Variations of the Sex
Hormone Pattern of Women in the Peri- and Post-Menopause
Menopause, which is caused by a lowering of the production of FEMale sex
hormones at the age around 50, can to many women generates unwanted symptoms
such as hot flushes, attacks of sweating, muscle and possibly joint pain,
sleep disturbances, dysphoria, nervousness, mood swings, headache,
palpitations (enhanced frequency of heart rate), dry mucous membranes and
pain during intercourse, urinary disturbances such as stress incontinent,
frequent passing water and pain/irritability of the bladder and urethra
during the process of passing water etc.
All these symptoms reflect age related changes which hitherto only have been
alleviated effectively by the administration of FEMale sex hormones like
estrogen and the like. By the administration of the present active
composition, previously known only as a remedy to alleviate symptoms related
to Pre-Menstrual Syndromes in common, surprisingly and unexpected a new
remedy is obtained, which can relieve and cure the symptoms obstructing the
normal life of women in the peri- and post-menopause without negative
adverse effects.
The menopause starts around the age of 48-55 years. Four out of 5 women have
disturbing menopause symptoms for at least one year and 25% of women have
menopause symptoms fore more than 5 years. Three out of four women suffer
from hot flushes and many women suffer from dysphoria, mood swings,
decreased libido etc. Half of all women have severe symptoms and in a
population of 5 million inhabitants, 200,000 women will constantly be in the
period of life where menopause trouble is disrupting their life.
Test Mode
Ten women with an average age of 50.8 (range from 46 to 55) years were
tested for the trial. All of them had been diagnosed to suffer from
climacteric disorders. The menstruation had ceased for 5 women while being
irregular for 5. None of the women obtained contemporaneous hormone therapy.
Each of the women obtained one tablet comprising the active ingredients in
an amount of 120.0 mg PI 82, 36.0 mg GC FEM and 6.0 mg Royal Jelly, twice
daily, morning and evening. The treatment did not affect pulse, or systolic
or diastolic blood pressure.
All trials related to VAS (visual analogous scales) on symptoms relating to
variations in the normal sex hormone pattern of women in the peri- and
post-menopause. The women obtained an interrogation formulae and were
requested to estate the symptoms disclosed in the formula according to a
scale from 1 to 4, wherein a higher value implies a better result. The
results of he tests are compiled in the enclosed Table 14. Low values
express favorable results. All statistical calculations are Wilcoxon test
for matched pairs, if not otherwise stated, VAS scales were performed on
menopausal hot flashes, tendencies of sweating, palpitations, sleep
disorders, vertigo, muscle pains, headache, difficulties in passing water (pollakuria),
stress incontinence, dysphoria, dry-vaginal and mucous membranes, arthralgia,
water retention (edema), irritability, and variations in mood.
The impact of active composition on different menopausal symptoms is shown
in Table 15. The participating women evaluated their conditions as regards
the symptoms disclosed in Table 15.
TABLE 15
The impact of active composition on different menopausal symptoms.
Mean value (standard deviation).
Treatment of Treatment of
active active
Without composition composition
Menopausal symptoms treatment 1 month 2 months
Hot flushes 3.08 (2.27) 2.81 (2.03) 1.33 (2.00)**
Sweating tendencies 3.94 (2.29) 2.75 (2.37) 1.73 (2.54)
Palpitations 2.66 (2.74) 1.88 (1.37) 1.31 (1.66)#
Muscle pain 3.40 (3.19) 2.19 (1.42) 2.08 (2.40)**
Headache 3.77 (2.84) 2.38 (2.20)*** 2.53 (1.98)***
Stress incontinence or 1.73 (2.34) 1.15 (1.44) 0.72 (0.85)#
frequent passing water
(pollakiuria)
Dysphoria 3.41 (2.05) 2.16 (1.27)* 1.60 (1.22)**
Dry vaginal and mucous 3.02 (2.88) 1.36 (1.31)*** 1.52 (2.32)***
membranes an/or pain
during intercourse
Joint pain 3.94 (2.82) 1.91 (1.03) 1.48 (1.30)**
Mood 3.05 (2.26) 2.72 (1.90) 1.73 (1.15)
Edema 6.04 (2.53) 4.48 (1.93)* 3.28 (1.59)**
Energy loss 4.99 (2.15) 3.82 (1.60)* 2.72 (2.21)***
Irritability 3.18 (2.55) 2.20 (1.78)*** 1.61 (1.24)*
Sleep disturbances 4.28 (3.89) 3.00 (3.07) 2.87 (3.09)
Mood swings 3.33 (2.16) 2.31 (1.07) 1.81 (1.63)#
Oversensitivity 4.03 (2.06) 2.70 (2.07)* 2.01 (1.79)**
# = border line significance
* = p < 0.05
** = p < 0.02
*** = p < 0.01
Hot flushes: significant (p<0.02) after two months.
Sweating tendencies: significant (p<0.05) after two months
Palpitations: more than 50% reduction (borderline significant).
Muscle pans: significant (p<0.02) after one month and borderline after two
months.
Headache: highly significant (p<0.01) after one and two months.
Stress incontinence and/or pollakuria: reduction of about 60%, borderline
significant.
Dysphoria: significant after one and two months (p<0.05 and p<0.02).
Dry vaginal or mucous membranes and/or pain during intercourse: significant
after one and two months (p<0.01 and p<0.01)>50% reduction.
Joint pain: significant after two months (p<0.02)
Mood: not significant, however a favorable change of about 40% is obvious.
Edema/water retention: reduction of more than 50%, significant after one and
two months (p<0.05 and p<0.02).
Energy loss: marked enhancement, significant after one and two months
(p<0.05 and p<0.01).
Irritability: reduced by 50% (p<0.01 and p<0.05).
Sleep disturbances show a tendency of effect but is not significant.
Mood swings: borderline significant after two months.
Oversensitivity: significant better after one and two months (p<0.05 and
p<0.02).
If all 19 VAS scores were added to a common "over all well being score" a
clearly positive effect is shown for 8 of 10 participants, only two were
unchanged. Thus, the improvement is significant (p<0.02).
At a direct inquiry of all ten participants whether they have had any
advantages or use of the treatment, 6 of them clearly said, "yes" while four
answered "don't know" (p<0.05, Chi square).
Below is given an Example of a tablet used according to the invention.
Active ingredients:
PI 82 (pollen pistil extract) 120.0 mg
GC FEM (pollen extract) 36.0 mg
Secondary ingredients:
ROYAL JELLY (freeze dried) 6.0 mg
VITAMIN E 50% 20.0 mg
Other ingredients:
Mikrocrystallin cellulose 87.0 mg
Dicalciumphosphate 87.0 mg
Magnesium stearate 4.0 mg
Uncoated tablet weight 360.0 mg
Coating:
Shellac approx. 2.64 mg
Talc approx. 0.36 mg
Total weight approx. 363.0 mg
Claim 1 of 16 Claims
What is claimed is:
1. A method for the treatment of symptoms related to normal hormonal
variations in women during fertile, peri- and post-menopausal age, by the
administration of a composition comprising, as active ingredients, a water
and/or fat-soluble cytosolic extract of pollen alone (GC FEM), an extract of
pollen and pistils (PI 82), or a combination of said extracts, optionally
combined with Royal Jelly and Vitamin E.
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