U.S. patent application number 16/447819 was filed with the patent office on 2020-12-24 for food supplement to alleviate symptoms of parkinson's disease.
The applicant listed for this patent is Muhammad Iqbal Choudhary, Atta-ur Rahman, Atia-tul Wahab, Humaira Zafar. Invention is credited to Muhammad Iqbal Choudhary, Atta-ur Rahman, Atia-tul Wahab, Humaira Zafar.
Application Number | 20200397846 16/447819 |
Document ID | / |
Family ID | 1000005261124 |
Filed Date | 2020-12-24 |
United States Patent
Application |
20200397846 |
Kind Code |
A1 |
Choudhary; Muhammad Iqbal ;
et al. |
December 24, 2020 |
FOOD SUPPLEMENT TO ALLEVIATE SYMPTOMS OF PARKINSON'S DISEASE
Abstract
A food supplement to reduce symptoms of Parkinson's disease is
disclosed. The food supplements contains a mixture of garlic,
almond, peanut, tomato, grape, clove, black eye pea turmeric, tea
and velvet bean.
Inventors: |
Choudhary; Muhammad Iqbal;
(Karachi, PK) ; Rahman; Atta-ur; (Karachi, PK)
; Wahab; Atia-tul; (Karachi, PK) ; Zafar;
Humaira; (Karachi, PK) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Choudhary; Muhammad Iqbal
Rahman; Atta-ur
Wahab; Atia-tul
Zafar; Humaira |
Karachi
Karachi
Karachi
Karachi |
|
PK
PK
PK
PK |
|
|
Family ID: |
1000005261124 |
Appl. No.: |
16/447819 |
Filed: |
June 20, 2019 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 36/8962 20130101;
A61K 36/736 20130101; A61K 36/87 20130101; A61K 36/82 20130101;
A61K 36/61 20130101; A61K 36/9066 20130101; A61K 36/81 20130101;
A61K 36/48 20130101; A61P 25/28 20180101 |
International
Class: |
A61K 36/8962 20060101
A61K036/8962; A61K 36/736 20060101 A61K036/736; A61K 36/48 20060101
A61K036/48; A61K 36/81 20060101 A61K036/81; A61K 36/87 20060101
A61K036/87; A61K 36/61 20060101 A61K036/61; A61K 36/9066 20060101
A61K036/9066; A61K 36/82 20060101 A61K036/82; A61P 25/28 20060101
A61P025/28 |
Claims
1. A method of reducing the symptoms of Parkinson's disease in
humans comprising administering a dose of 600 mg/kg to 1000 mg/kg
of an aqueous mixture of one-part Allium sativum L. (as fresh juice
of rhizomes), two parts Prunus dulcis (Mill.) D. A. Webb. (as dry
fruit powder), two parts Arachis hypogaea L. (as dry fruit powder),
two parts Solanum lycopersicum L. (as fruit dried under shade and
then powdered), ten parts Vitis vinifera L. (as fresh juice), 0.1
parts Eugenia caryophyllata Thunb. (as seed oil), two parts Vigna
unguiculata L. (as dried seed powder), one-part Curcuma longa L.
(as rhizome powder), 0.72 parts Camellia sinensis L (as leaf
extract), and two parts Mucuna purines L. (as roasted seed powder)
to humans in need for the treatment.
2. (canceled)
3. (canceled)
4. The method of claim 3, wherein the said composition further
contains suitable inactive pharmaceutical ingredients.
5. (canceled)
Description
BACKGROUND OF THE INVENTION
[0001] The worldwide prevalence of Parkinson's disease (hereinafter
PD) ranges between 5 to 35 per 0.1 million individuals annually.
The disease is rare before the age of 50 years, and the incidence
increases 5-10 fold in age groups of 60-90 years. The clinical
symptoms of Parkinson's disease include bradykinesia, rigidity, or
tremors. The onset of motor symptoms is unilateral throughout the
disease. Furthermore, many patients with Parkinson's disease also
possess non-motor symptoms, including cognitive impairment,
disorders of sleep and mood, autonomic dysfunctions, and
disturbance in sensory symptoms. The cardinal motor symptoms of
Parkinson's disease are the result of degeneration of dopaminergic
neurons in brain (the substantia nigra pars compacta) that leads to
dopamine depletion.
[0002] Due to the complexity of Parkinson's disease, its treatment
requires a combination of medical, complementary, and supportive
therapies, including exercise, massage, speech therapy,
rehabilitation, diet, etc. With the deeper understanding of the
mechanisms that regulate the dopaminergic transmission in
nigrostriatal regions, various pharmacological targets have been
identified for dopaminergic therapies.
[0003] Parkinson's disease has no cure, although treatments are
available that help to manage the symptoms, and maintain the
quality of life. The drugs for the treatment of PD are categorized
into three types, including drugs that help to increase the level
of dopamine, drugs that affect the level of acetylcholine, and the
one that help to control the non-motor symptoms. All these
pharmacological treatments have their own limitations, and are
associated with adverse effects. For instance, dopamine agonist can
execute significant risks for individuals with cardiovascular
diseases, depression, or renal insufficiency.
[0004] Currently, the treatment of PD patients involves the use of
different drugs in combination, based on the tolerance level of
individual patients to cope up with the adverse effects of these
drugs. Sooner or later the drugs need to be changed as they become
ineffective. Majority of the Parkinson's disease patients undergo a
gradual decline in their health as the nervous system has already
weakened. This health decline ultimately leads to severe
disability. Moreover, the medicines and care of these patients are
costly, and are required for entire remaining life.
[0005] Therefore, there is an urgent need to develop effective,
safe, and less-expensive approaches for the management of the PD
symptoms. This can be done by using natural sources to manage PD
symptoms that will have lesser adverse effects on quality of life.
Various medicinal and dietary plants and natural products have been
reported to possess anti-Parkinson's effects. Based on this
hypothesis, we have developed a new dietary health supplement for
the management and/or treatment of Parkinson's disease. Only
mineral water was used to mix the ingredients. The resulting
formulation can be used in humans as the dietary health supplement,
and has no chemical based ingredients. It is, therefore, safe,
effective, and non-toxic.
BRIEF SUMMARY OF THE INVENTION
[0006] Parkinson's disease is a neurodegenerative disorder that has
various layers of complexities. Till date, there is no cure for the
disease but the only aim is to manage the motor and non-motor
symptoms of PD. Different types of drugs are available to manage
the symptoms of PD, including dopamine agonists, non-dopaminergic
agents, and catechol-o-methyl-transferase (COMT) inhibitors.
However, with the passage of time, the effects of these drugs
decrease, followed by adverse effects such as dyskinesia,
hallucination, sleepiness, and many others. The current research on
neurological diseases, therefore emphasizes on the use of
nutritional supplements so that the adverse effects can be
minimized, along with improvement in life style of these
patients.
[0007] Based on these facts, an extensive literature survey was
carried out and the dietary plants reported for anti-Parkinson's,
antioxidant, and neuroprotective effects were selected. This
includes Allium sativum L., Prunus dulcis (Mill.) D. A. Webb.,
Arachis hypogaea L., Solanum lycopersicum L., Vitis vinifera L.,
Eugenia caryophyllata Thunb., Vigna unguiculate L., Curcuma longa
L., Camellia sinensis L., and Mucuna puriens L. The ingredients
were mixed using pure mineral water, and no organic solvent was
used. The effect of this dietary health supplement was
pre-clinically studied in animal model of Parkinson's disease (Male
Wistar rats). The supplement was able to significantly improve the
PD symptoms in rats. 37.5% Rats at score 8 showed improvement in PD
symptoms, and were decreased to scores 4 and 2 (with better
mobility, stable postural stability, and white furs except
tremors). 100% Rats with score 4 and 6 showed improvements in their
PD symptoms, and their scores were lowered to 2. 100% Rats at score
2 showed improvement in various PD symptoms. such as better
mobility, stable postural ability, and white furs except tremors
that were not treated completely in any rat. The acute toxicity
studies of testing health supplement was carried out according to
OECD guidelines at 2,000, and 5,000 mg/kg. The supplement did not
show any toxic effect during the toxicity studies in animals. The
chronic toxicity has also been tested for 3 months, and no adverse
effect was seen in the animals.
[0008] Open label clinical trials on a small group of PD patients
were also conducted under the supervision of experienced
neurologists. The health supplement has caused a significant
improvement in the symptoms of PD, such as improved speech and
clarity in words, and voice, sensory input (Patient can sense
before falling down and can hold any object to be stable), relief
in muscular pain specially in legs and feet, decreased drowsiness,
increased physical activity, and improved body balance (helps
patient to walk properly). Therefore, it is concluded that the use
of this supplement can help to improve the quality of life in PD
patients, and additionally it has no adverse effects
whatsoever.
DETAILED DESCRIPTION OF THE INVENTION
[0009] The dietary supplement is composed of ten dietary plant
materials, mixed in a specific proportion. The components include
Allium sativum L., Prunus dulcis (Mill.) D. A. Webb., Arachis
hypogaea L., Solanum lycopersicum L., Vitis vinifera L., Eugenia
caryophyllata Thunb., Vigna unguiculate L., Curcuma longa L.,
Camellia sinensis L., and Mucuna pruriens L. Only mineral water has
been used to mix the ingredients. The detailed description for the
selection of above mentioned dietary plants are described
below:
[0010] The rhizomes of Allium sativum L. (garlic) were selected due
to its reported anti-PD effect. Fresh garlic cloves/garlic capsules
have shown significant effects in PD patients. Dry fruits of Prunus
dulcis (Mill.) D. A. Webb (almond), and Arachis hypogaea L.
(peanuts) were selected due to their reported neuroprotective, as
well as antioxidant effects. Fruits of Solanum lycopersicum L.
(tomato) were used due to their reported anti-PD effect. Fruits of
Vitis vinifera L. (red grapes) are reported for antioxidant
effects, and their ability to help in neuronal survival. Oil of
Eugenia caryophyllata Thunb. (clove) was used as it has been
reported for anti-PD effect. Dry seeds of Vigna unguiculata L.
(black eyed cowpea) was selected due to the presence of 0.45%
L-DOPA.
[0011] The rhizomes of Curcuma longa L. (turmeric) were selected as
they reported to protect the dopaminergic neurons against
.alpha.-synuclein induced neurotoxicity. Leaves of Camellia sinesis
L. (green tea) were selected as they are widely reported for their
neuroprotective, and antioxidant effects. Green tea is also
reported to attenuate the dopamine depletion, and increase
dopaminergic neuronal survival in MPTP induced PD model. Seeds of
Mucuna puriens L. (velvet beans) are a rich source of L-DOPA so it
was selected for this anti-PD formulation.
Procedure for the Preparation of Dietary Health Supplement
TABLE-US-00001 [0012] i. Allium sativum L. Fresh juice of rhizomes
ii. Prunus dulcis (Mill.) D. A. Webb. Dry fruit powder iii. Arachis
hypogaea L. Dry fruit powder iv. Solanum lycopersicum L. Fruit
dried under shade and then powdered v. Vitis vinifera L. Fresh
juice vi. Eugenia caryophyllata Thunb. Seed oil vii. Vigna
unguiculata L. Dried seed powder viii. Curcuma Longa L. Rhizome
powder ix. Camellia sinesis L. Leaves extract x. Mucuna purines L.
Roasted seed powder
[0013] The supplement including Allium sativum L., Prunus dulcis
(Mill) D. A. Webb., Arachis hypogaea L., Solanum lycopersicum L.,
Vitis vinifera L., Eugenia caryophyllata thunb., Vigna unguiculate
L., Curcuma longa L., Camellia sinensis L., and Mucuna pruriens L.
were mixed in a ratio of 1:2:2:2:10:0.1:2:1:0.7:2,
respectively.
Pre-Clinical Studies of Dietary Health Supplement in Rat Model of
Parkinson's Disease:
[0014] The development of PD does not occur naturally in animals,
except in humans. Therefore, different models are used to induce PD
symptoms in animals, such as 6-hydroxydopamine (6-OHDA),
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or rotenone
are used to induce nigrostriatal dopaminergic lesions. In the
current study, we have used rotenone-based in vivo assay for PD as
it is the most relevant model among the available assays.
[0015] Rotenone is naturally occurring plant flavonoid, and a
well-known neurotoxic pesticide that readily cross the blood-brain
barrier due to its high lipophilic nature. It inhibits the
mitochondrial complex-I of the electron transport chain (ETC),
followed by ROS production. Nearly, all hallmarks of PD are
replicated in rotenone induced animal model. It can be administered
via intravenous (IV), intraperitoneal (IP), or oral route.
[0016] We developed the rotenone induced model, in which rats were
injected with 2 mg/kg rotenone subcutaneously (s.c.) for
consecutive 28 days. The rats were daily observed for various PD
symptoms, such as piloerection, decrease mobility, tremors, and
many others. Based on the observations of symptoms, rats were
scored between 2-10, where 2 refers to lowest and 10 is highest PD
score, as previously reported by Chen Xin and his colleagues
(17-19). Following is the details scoring system that was used in
PD model.
[0017] Scoring Criteria for Study Design II: [0018] [21] Score 2:
apart from the above indications, active mobility was reduced more
obviously, and was accompanied with tremor, slow motion, and gait
instability. [0019] [22] Score 4: apart from the above indications,
gait instability worsened, and the rats could not walk straight,
rotating towards one side. [0020] [23] Score 6: apart from the
above performance, they lay obliquely towards one side or showed
unilateral forelimb or hindlimb paralysis, and difficulty in
walking and eating. [0021] [24] Score 8: complete unilateral limb
(forelimb or hindlimb) paralysis, limb spasms, rapid weight loss,
and inability to eat. [0022] [25] Score 10: agonal stage or
death
[0023] PD Model of Male Wistar Rats: In vivo rat PD model was
developed, and the pre-clinical trials were conducted after the
approval of the ICCBS ethical committee (ASP #2018-0007). 3 Months
old, male Wistar rats (217 rats) were randomly divided into four
groups, including control, pathological, standard drug, and
supplement treated groups. The control group (10 rats) were s.c.
injected with vehicle (myglyol 98%, DMSO 2%) only, and were used as
reference. The remaining 210 rats were injected with rotenone (2
mg/kg) (dissolved in myglyol 98%, DMSO 2%) for 7-28 consecutive
days depending on the appearance of PD symptoms. The animals were
analyzed individually on daily basis and were scored accordingly.
Among 210 rats, various PD symptoms were observed in 117 rats,
while the remaining 93 rats did not show any signs or symptoms of
PD. Therefore, 117 rats were further divided into pathological
group (35 rats), standard drug treated (30 rats), and supplement
treated (49 rats).
[0024] Pathological Group: The pathological/disease group included
rats with score 2, 4, 6, and 8. These animals were left untreated
after their respective scores, and were observed for the
self-reversal of Parkinson's disease symptoms including motor
(tremors, gait instability, decrease mobility, complete hind limb
or fore limb paralysis), and non-motor symptoms (bad furs,
piloerection, inability to eat, loss of body weight).
[0025] Among 35 pathological control rats, score 8 was observed in
10 rats, score 6 was observed in 7 rats, score 4 was observed in 8
rats, and score 2 was observed in 10 rats. The score 8 animals
became completely paralyzed, and were not able to eat or drink
independently so they were given the food and water using oral
gavage.
[0026] Among score 8, only two rats (20% rats) showed self-reversal
in PD symptoms, and move to score 4, and 6. However, conditions of
remaining rats of score 8 (80% rats) became worsen and they moved
to score 10 (death).
[0027] Among score 6 animals, two rats (28.5%) showed minor
self-reversal in PD symptoms and move to score 4, while condition
of one rat (14.2%) became worsen and moved to score 10 (death).
However, remaining four rats (57.1%) were consistent at their
developed PD score.
[0028] Among score 4 animals, four rats (50%) showed a minor
self-reversal in PD symptoms and moved to score 2, while remaining
four rats (50%) were remain consistent at their developed PD score.
Among score 2 animals, all ten rats (100%) were consistent at their
developed PD score.
[0029] Standard Drug Treated Group: Total 30 rats with scores 4, 6,
and 8 were selected for the treatment with standard drug (Sinemet,
a mixture of Carbidopa/Levodopa), which is the most successful drug
approved by the U.S. Food and Drug Administration (FDA) for the
treatment of symptoms associated with Parkinson's disease.
According to the literature survey, patients can take up to the 5
tablets, depending upon the severity of the symptoms (20). The
treatment dose is calculated using the Human Equivalent Dose of
Parkinson Patients. Among 30 rats, score 8 was observed in 13 rats,
score 6 was observed in 8 rats, and score 4 was observed in 9
rats.
[0030] Rats of score 8 were given 51 mg Sinemet/kg body weight.
Among score 8 rats, only three (23% rats) showed improvement in PD
symptoms and moved to score 6. However, conditions of remaining
rats of score 8 (77% rats) became worsen, as they moved to score 10
(death).
[0031] Rats of score 6 were given 41 mg Sinemet/kg body weight.
Among them, four rats (50%) showed improvement in PD symptoms, and
move to score 4 and 2. However, two rats (25%) were consistent at
their PD score and did not show any improvement in their
conditions. Conditions of remaining two rats (25% rats) became
worsen, and they moved to score 10 (death).
[0032] Rats of score 4 were given 31 mg Sinemet/kg body weight.
Among them, only two rats (22%) showed improvement in PD symptoms
and they move to score 2. However, conditions of one rat (11%)
became worsen and moved to score 10 (death). Remaining five rats
(55%) were consistent at their PD score and did not show any
improvement in their conditions.
[0033] Supplement Treated Group: A total of 49 rats with scores 2,
4, 6, and 8 were selected for the treatment with supplement. Among
49 rats, score 8 was observed in 16 rats, score 6 was observed in 9
rats, score 4 was observed in 14 rats, and score 2 was observed in
10 rats.
[0034] Rats of score 8 were given supplement 2,000 mg/kg body
weight. Among score 8, 6 rats (37.5% rats) showed improvement in PD
symptoms and move to scores 4, and 2. However, conditions of
remaining 10 rats (62.5% rats) became worsen and they moved to
score 10 (death). These results were significant, in comparison to
the standard drug treated group as the improvement was seen in only
23% rats.
[0035] Rats of score 6 were given supplement at a dose of 1,000
mg/kg body weight. All rats (100%) showed improvement in PD
symptoms, and move to score 2.
[0036] Rats of score 4 were given supplement 600 mg/kg body weight.
Among them, 13 rats (92.8%) showed improvement in PD symptoms, and
move to score 2. Remaining one rat (7.2%) was consistent at its PD
score, and did not show any improvement in its conditions.
[0037] Rats of score 2 were given supplement at a dose of 600 mg/kg
body weight. Rats in this group showed improvement in various
symptoms of score 2. For instance, their mobility was restored to
normal, gait instability was decreased; and furs became white (back
to normal). Only tremors and piloerection were not treated, so they
were still considered at score 2.
[0038] In conclusion, rats in the group treated with dietary health
supplement showed significantly improved behaviors, and had lower
PD scores as compared to the pathological and drug treated groups.
Whereas no improvement in PD symptoms was observed in 77% rats of
pathological group indicating that the rotenone induced symptoms
were not significantly reversed.
[0039] Acute and Chronic Toxicity of Testing Dietary Health
Supplement: The pre-clinical toxicological studies of dietary
health supplement have been carried out to determine the safety
profile of this novel dietary formulation. The protocol based on
OECD guidelines (20, 21) were used to study acute and chronic
toxicity studies of dietary health supplement.
[0040] Protocol for The Acute and Chronic Toxicity Studies: Animals
were divided into three groups with 10 animals per sex in each
group. Group I served as blank, and was left untreated. Group II
animals were given a single dose of 2,000 mg/kg dietary health
supplement through oral gavage. Group III animals were given a
single dose of 5,000 mg/kg dietary health supplement through oral
gavage. Rats were carefully observed for the development of any
toxic signs or symptoms for first 30 mins, and periodically (i.e.
60, 120, 240, and 360 mins, and then after 24 hours), and
thereafter daily for consecutive 14 days.
[0041] Physical observation of animals included changes in skin
colour (fur), lacrimation (red tears due to pain), salivation,
piloerection (bristling or erection of hairs), frequent urination,
tremors, convulsions, drowsiness, body weight, food consumption,
and water consumption. The death of animals was also observed as
mortality rate. After the completion of physical observation for 14
days', animals were dissected for the biochemical, and pathological
studies.
[0042] Biochemical parameters of animals including blood glucose,
creatinine, urea, liver function test, lipid profile, and complete
blood count (CBC) were also analysed. Pathological studies of
animals included the gross anatomical examination of vital organs
including heart, liver, spleen, lungs, stomach, and kidneys.
[0043] For chronic toxicity, animals were divided into four groups
with 10 animals each per sex in each group. Group I served as blank
and was untreated. Group II, III, and IV animals were given doses
of 925, 1850, and 3,700 mg/kg dietary health supplement through
oral gavage consecutively for 3 months. As the supplement was found
to be non-toxic in acute toxicity studies, so this time the rats
were observed on daily basis for the physical symptoms (mentioned
above), while the body weights were recorded weekly. After 3
months, the rats were dissected for biochemical tests, and gross
pathology studies.
[0044] Results of Acute Toxicity: The animals were physically
observed for various parameters. No change in skin or fur colour
was observed, before and after the administration of dietary health
supplement till 14 days. Lacrimation i.e., the secretion of tears
from the eyes of rats, was not observed. Usually when rats are
stressed or ill their eyes become red due to release of a red
pigment called porphyrin. Urination was also found to be normal,
indicating that the dietary health supplement is not inducing any
kind of inflammation neither is affecting the kidneys. Salivation
was also found to be normal. The food and water consumption in rats
after the administration of dietary health supplement was also
found to be normal.
[0045] There were no toxic signs and no mortality was observed
after 14 days of administration of dietary health supplement. The
animals were sacrificed, and the samples were analysed for
biochemical tests, such as blood glucose, liver function test, CBC,
and lipid profile. All biochemical parameters after the
administration of dietary health supplement were found to be within
the normal range indicating that the dietary supplement was not
toxic for the rats upto a dose of 5,000 mg/kg. Based on the
above-mentioned results it has been concluded that the dietary
health supplement at the dose of 5,000 mg/kg is found to be safe
during the acute toxicity studies. There was no significant change
in the body weight, food, and water consumption was observed.
[0046] Heart, liver, spleen, kidneys, stomach, and lungs of rats
from all groups were preserved in formalin for gross necropsy. The
absolute and relative weights of organs after the administration of
dietary health supplement were observed. There was no change in the
relative and absolute weight of every organ in the animals,
indicating that the supplement is safe to be used at a dose of
5,000 mg/kg. Furthermore, no mortality was observed till 14 days
after administration of dietary health supplement.
[0047] Results of Chronic Toxicity: Three different doses of
dietary health supplement i.e. 925, 1850, and 3,700 mg/kg body
weight (representing half of the Human Equivalent dose, the Human
Equivalent dose, and double the Human Equivalent dose,
respectively, were given to Albino Wistar rats (male and female)
for 3 months. In chronic toxicity testing, all animals were
observed daily for the development of any toxic signs or symptoms
for 3 months.
[0048] Biochemical tests, such as blood glucose, liver function
test, CBC, and lipid profile were also carried out. All the
biochemical parameters after the administration of dietary health
supplement were found to be within the normal range, indicating
that the dietary supplement was not toxic for the rats up to the
dose of 3,700 mg/kg. Based on the above-mentioned results it has
been concluded that the dietary health supplement up to the dose of
3,700 mg/kg was safe to animals during the chronic toxicity
studies.
[0049] Brain, liver, and kidneys were preserved in formalin for
histopathology studies. The absolute and relative weights of
different organs after the administration of dietary health
supplement were observed. There was no change in the relative and
absolute weight of every organ in the animals, indicating that the
supplement is safe to be used upto a dose of 3,700 mg/kg.
* * * * *