Note: Descriptions are shown in the official language in which they were submitted.
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
TITLE
COMPOSITIONS AND METHODS FOR IMPROVED ORAL HEALTH
BACKGROUND
[0001] The present disclosure is direct to medical treatments. More
specifically,
the present disclosure is directed to compositions and methods for improving
the oral
health of an individual.
[0002] Epidemiological studies estimate a prevalence rate for dysphagia among
those over the age of 5 years to be 16% to 22% among individuals. There are 2
broad
categories of dysphagia: (i) esophageal dysphagia, and (ii) oral pharyngeal
dysphagia.
[0003] Esophageal dysphagia affects a large number of individuals of all ages,
but
is generally treatable with medications and is considered a less serious form
of dysphagia.
Esophageal dysphagia is often a consequence of mucosal, mediastinal, or
neuromuscular
diseases. Mucosal (intrinsic) diseases narrow the lumen through inflammation,
fibrosis,
or neoplasia associated with various conditions (peptic stricture secondary to
gastroesophageal reflux disease, esophageal rings and webs [sideropenic
dysphagia or
Plummer-Vinson syndrome], esophageal tumors, chemical injury [e.g., caustic
ingestion,
pill esophagitis, sclerotherapy for varices], radiation injury, infectious
esophagitis, and
eosinophilic esophagitis). Mediastinal (extrinsic) diseases obstruct the
esophagus by
direct invasion or through lymph node enlargement associated with various
conditions
(tumors [e.g., lung cancer, lymphoma], infections [e.g., tuberculosis,
histoplasmosis], and
cardiovascular [dilated auricula and vascular compression]). Neuromuscular
diseases may
affect the esophageal smooth muscle and its innervation, disrupting
peristalsis or lower
esophageal sphincter relaxation, or both, commonly associated with various
conditions
(achalasia [both idiopathic and associated with Chagas disease], scleroderma,
other
motility disorders, and a consequence of surgery [i.e., after fundoplication
and antireflux
interventions]). It is also common for individuals with intraluminal foreign
bodies to
experience acute esophageal dysphagia.
1
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
[0004] Oral pharyngeal dysphagia, on the other hand, is a very serious
condition
and is generally not treatable with medication. Oral pharyngeal dysphagia also
affects
individuals of all ages, but is more prevalent in older individuals.
Worldwide, oral
pharyngeal dysphagia affects approximately 22 million people over the age of
50. Oral
pharyngeal dysphagia is often a consequence of an acute event, such as a
stroke, brain
injury, or surgery for oral or throat cancer. In addition, radiotherapy and
chemotherapy
may weaken the muscles and degrade the nerves associated with the physiology
and
nervous innervation of the swallow reflex.
[0005] It is also common for individuals with progressive neuromuscular
diseases,
such as Parkinson's Disease, to experience increasing difficulty in swallowing
initiation.
Representative causes of oropharyngeal dysphagia include those associated
neurological
illnesses (brainstem tumors, head trauma, stroke, cerebral palsy, Guillain-
Barre syndrome,
Huntington's disease, multiple sclerosis, polio, post-polio syndrome, Tardive
dyskinesia,
metabolic encephalopathies, amyotrophic lateral sclerosis, Parkinson's
disease, dementia),
infectious illnesses (diphtheria, botulism, Lyme disease, syphilis, mucositis
[herpetic,
cytomegalovirus, candida, etc.], autoimmune illnesses (lupus, scleroderma,
Sjogren's
syndrome), metabolic illnesses (amyloidosis, cushing's syndrome,
thyrotoxicosis,
Wilson's disease), myopathic illnesses (connective tissue disease,
dermatomyositis,
myasthenia gravis, myotonic dystrophy, oculopharyngeal dystrophy,
polymyositis,
sarcoidosis, paraneoplastic syndromes, inflammatory myopathy), iatrogenic
illnesses
(medication side effects [e.g., chemotherapy, neuroleptics, etc.], post
surgical muscular or
neurogenic, radiation therapy, corrosive [pill injury, intentional]), and
structural illnesses
(cricopharyngeal bar, Zenker's diverticulum, cervical webs, oropharyngeal
tumors,
osteophytes and skeletal abnormalities, congenital [cleft palate,
diverticulae, pouches,
etc.]).
[0006] Aspiration pneumonia is a common clinical consequence of dysphagia.
The condition often requires acute hospitalization and emergency room visits.
Among
those that develop pneumonia due to aspiration, the differential diagnosis of
"aspiration
pneumonia" is not necessarily indicated as a result of current care practices.
2
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
[0007] Based on US healthcare utilization surveys from recent years, pneumonia
accounted for over 1,000,000 hospital discharges and an additional 392,000
were
attributable to aspiration pneumonia. Individuals who have general pneumonia
as the
principal diagnosis have a mean 6 day hospital length of stay and incur over
$18,000 in
costs for hospital care. It is expected that aspiration pneumonia would carry
higher costs
for hospital care based on a mean 8 day length of hospital stay.
[0008] Pneumonia is life threatening among persons with dysphagia, and the
odds
of death within 3 months is -50%. In addition, an acute insult such as
pneumonia often
initiates the downward spiral in health among elderly. An insult is associated
with poor
intakes and inactivity, resulting in malnutrition, functional decline, and
frailty. For
example, elderly commonly aspirate oropharyngeal contents during sleep.
[0009] The risk of aspiration pneumonia is greatest when periodontal disease,
dental caries and poor oral hygiene are compounded by swallowing disease,
feeding
problems and poor functional status. Aspiration pneumonia is thought to be
caused by the
aspiration of colonized nasopharynx or oropharynx material secondary to
dysphagia.
Forceful coughing, active ciliary transport and normal immune response are
presumed to
be protective but are inadequate. Microflora present in the oral cavity
because of poor
oral hygiene have been associated with aspiration pneumonia.
[0010] The current standard of care for reducing incidence of aspiration
pneumonia in patients with clinically-diagnosed swallowing disorders is
chemical
disinfection and use of antimicrobial agents to improve oral health.
Additionally, another
method called selective decontamination is used. This method is a prophylactic
technique
in which antimicrobials eradicate aerobic gram negative bacteria from the
oropharynx
while preserving the normal oral microbial flora. The agents include oral
antimicrobial
gels with antibiotics, liquid suspensions with same administered through a
nasogastric
("NG") tube, intravenous ("IV") antibiotics and stringent infection control.
While this
method is superior to use of broad spectrum antibiotics that indiscriminately
eradicate all
bacteria (beneficial and harmful), it does not re-inoculate the oral cavity
with the
beneficial bacterial thus the patient does not re-establish balanced
microflora and remains
susceptible to onset of oral infections such as C. albicans (thrush).
3
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
[0011] The use of selective decontamination is also limited due to the risk of
bacterial developing resistance to the antibiotics. In addition, the efficacy
of this
procedure in reducing aspiration pneumonia is questionable as in a recent meta-
analysis, it
was concluded that oral decontamination with chlorhexidine ("CHX") could
prevent
ventilator associated pneumonia, but the strategy does not reduce the time on
ventilator,
the length of stay in the intensive care unit ("ICU") or rates of mortality.
SUMMARY
[0012] The present disclosure relates to compositions and methods for
preventing
and treating illnesses associated with oral health. In a general embodiment,
the
compositions and methods of the present disclosure can provide: (i) a
reduction in the
incidence of aspiration pneumonia, (ii) less gingivitis and plaque, and (iii)
improved
tongue flora. The source of chronic microbial challenge to the host can be
targeted, which
can reduce chronic inflammation on the host, help to restore an adequate
immune
response to physiological challenges and reduce an individual's risk of
infections. By
preventing and treating problems associated with oral health in a patient,
subsequent
health problems can be prevented or mitigated, which can result in reduced
health care
costs for the patient in the future.
[0013] In a general embodiment, the present disclosure provides a nutritional
composition for improving oral health. The composition includes a
therapeutically
effective amount of a beneficial bacteria such as Lactobacillus reuteri,
Lactobacillus
plantarum, streptococcus Salivarius, Streptococcus salivarius K12,
Lactobacillus reuteri
ATCC55730, Lactobacillus johnsonii Lal, Lactobacillus plantarum 299v,
Lactobacillus
rhamnosus GG Streptococcus thermophilus NCC 1561, Lactococcus lactis NCC2211
(Pelargon strain), and Lacteol, and Other Ingredients with desired properties
in
accordance with the present invention include: CGMP which has been shown in
testing
to prevent binding of pathogens or a combination thereof. The beneficial
bacteria can
include one or more bacteria normally indigenous to the oral cavity. For
example, the
beneficial bacteria can include one or more strains normally indigenous to the
oral cavity
4
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
such as streptococcus Salivarius K12, Lactobacillus platarum 299,
Lactobacillus
platarum 299v or a combination thereof. The beneficial bacteria can be living
or
inactivated.
[0014] In an embodiment, the composition is in a form such as liquids, solids,
semisolids or a combination thereof. The composition can be a complete oral
nutritional
supplement. The composition can also be in a form such as lozenges, lollipops,
sachets,
dissolvable films or a combination thereof.
[0015] In an embodiment, the composition is in a form such as a food, a
beverage
and combinations thereof. The composition can include an ingredient such as a
thickener.
In an alternative embodiment, the composition is a topical compound that can
be applied
to the surface of the oral cavity.
[0016] In another embodiment, the present disclosure provides a method of
reducing the incidence of aspiration pneumonia. The method comprises
administering to
a patient at risk of or having aspiration pneumonia a therapeutically
effective amount of a
composition comprising a beneficial bacteria selected from the group
consisting of
Lactobacillus reuteri, Lactobacillus plantarum, streptococcus Salivarius,
Streptococcus
salivarius K12, Lactobacillus reuteri ATCC55730, Lactobacillus johnsonii Lal,
Lactobacillus plantarum 299v, Lactobacillus rhamnosus GG Streptococcus
thermophilus
NCC 1561, Lactococcus lactis NCC2211 (Pelargon strain), and Lacteol, and Other
Ingredients with desired properties in accordance with the present invention
include:
CGMP which has been shown in testing to prevent binding of pathogens and
combinations thereof.
[0017] In an alternative embodiment, the present disclosure provides a method
of
improving oral health. The method comprises administering to a patient at risk
of or
having oral health problems a composition comprising a therapeutically
effective amount
of a beneficial bacteria selected from the group consisting of Lactobacillus
reuteri,
Lactobacillus plantarum, streptococcus Salivarius, Streptococcus salivarius
K12,
Lactobacillus reuteri ATCC55730, Lactobacillusjohnsonii Lal, Lactobacillus
plantarum
299v, Lactobacillus rhamnosus GG Streptococcus thermophilus NCC 1561,
Lactococcus
lactis NCC2211 (Pelargon strain), and Lacteol, and Other Ingredients with
desired
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
properties in accordance with the present invention include: CGMP which has
been
shown in testing to prevent binding of pathogens and combinations thereof.
[0018] In yet another embodiment, the present disclosure provides a method of
reducing healthcare costs. The method comprises administering to a patient at
risk of or
having oral health problems a composition comprising a therapeutically
effective amount
of a beneficial bacteria selected from the group consisting of Lactobacillus
reuteri,
Lactobacillus plantarum, streptococcus Salivarius, Streptococcus salivarius
K12,
Lactobacillus reuteri ATCC55730, Lactobacillusjohnsonii Lal, Lactobacillus
plantarum
299v, Lactobacillus rhamnosus GG Streptococcus thermophilus NCC 1561,
Lactococcus
lactis NCC2211 (Pelargon strain), and Lacteol, and Other Ingredients with
desired
properties in accordance with the present invention include: CGMP which has
been
shown in testing to prevent binding of pathogens. and combinations thereof.
The
reduction in healthcare costs can be due to decreased incidences of aspiration
pneumonia
or general pneumonia that may not be differentially diagnosed. Alternatively,
the
reduction in healthcare costs can be due to a reduced treatment of secondary
infections
and/or prevention of a downward spiral in health. This can include, for
example, loss of
functionality, frailty, disability and death.
[0019] The reduction in healthcare costs be due to improved overall health of
the
patient or due to decreased dental costs. The reduction in healthcare costs
can be due to
decreased utilization of hospitals and skilled nursing facilities. Decreased
utilization can
be fewer days, fewer number of admissions, fewer ER visits, decreased
incidences of
aspiration pneumonia. The reduction in healthcare costs can also be due to
decreased
utilization of specialized care.
[0020] The reduction in healthcare costs can also be due to decreased
utilization of
antibiotics and/or artificial ventilation and/or pulmonary rehabilitation
and/or physical
therapy post-ventilation and/or intravenous fluids. The decreased utilization
can be due to
a decreased need for prevention of aspiration pneumonia. The decreased
utilization can
be due to treatment of sequellae from antibiotic use. The sequellae can be
fungal
infections (thrush), or urinary tract infections ("UTI5"), or C. dijcile
associated diarrhea
or a combination thereof. The sequellae can also be infections from antibiotic
resistant
6
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
bacteria, methicillin-resistant Staphylococcus aureus, or a combination
thereof. The
decreased sequellae from antibiotic use can be due to decreased incidences of
infections
from antibiotic resistant bacteria.
[0021] An advantage of the present disclosure is to provide a composition for
improving oral health.
[0022] Another advantage of the present disclosure is to provide a method for
improving oral health.
[0023] Yet another advantage of the present disclosure is to provide a method
for
reducing the incidence of aspiration pneumonia.
[0024] Still another advantage of the present disclosure is to provide a
method of
reducing health care costs.
[0025] Additional features and advantages are described herein, and will be
apparent from the following Detailed Description.
DETAILED DESCRIPTION
[0026] The present disclosure relates to compositions and methods for
preventing
and treating illnesses associated with oral health. In alternative
embodiments, the
compositions and methods can be used to reduce improve oral health such
reducing the
incidence of aspiration pneumonia. The compositions and methods can also be
used to
reduce the healthcare costs associated with treating the effects of adverse
oral health
conditions.
[0027] It has been surprisingly found that using a therapeutically effective
amount
of bacteria or probiotics naturally present in the oral cavity can reduce
anaerobic gram-
negative bacilli ("AGNB") and increase the presence of the normal flora
thereby re-
introducing the good bacterial to the mouth without increasing the risk of
antibiotic
resistance or antibiotic-associated adverse outcomes. Additionally, side
effects such as
discoloration of the teeth, irritation of mucosa or even serious allergic
reactions can be
mitigated or eliminated. As the selected probiotics will have beneficial
systemic effects,
patients can benefit not only from the localized improvement of oral health
(with
7
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
important end benefit of reduced aspiration pneumonia), but also improved
general
immunity.
[0028] The compositions and methods in embodiments of the present disclosure
are beneficial for individuals or patients with clinical (diagnosed),
subclinical
(undiagnosed), or at risk of disorders of swallowing. Patients with swallowing
difficulties
such as those clinically diagnosed with dysphagia or those at risk of
developing dysphagia
can be malnourished or elderly and have Parkinson's, Alzheimer disease,
dementia, head
and neck cancer, stroke, Down's syndrome or conditions leading to protruded
tongue.
[0029] The compositions and methods can provide health benefits to patients at
risk or having silent aspiration (e.g. aspirate during sleep or any other time
such as while
reclined) and those at risk of or who have had pneumonia (e.g. recurrent
pneumonias,
immune-compromised persons). In addition, the compositions and methods can
provide
health benefits to those who are at risk of or have poor oral health (e.g.
secondary to
medication use, decreased saliva production, smoking/tobacco use, alcohol use,
liver
failure, infrequently practice oral hygiene methods, functionally-impaired who
require
assistance with oral care).
[0030] As used herein the term "patient" is preferably understood to include
an
animal, especially a mammal, and more especially a human that is receiving or
intended to
receive treatment, as it is herein defined.
[0031] As used herein, "mammal" includes but is not limited to rodents,
aquatic
mammals, domestic animals such as dogs and cats, farm animals such as sheep,
pigs,
cows and horses, and humans. Wherein the term mammal is used, it is
contemplated that
it also applies to other non-mammal animals that are capable of the effect
exhibited or
intended to be exhibited by the mammal.
[0032] As used herein, "complete nutrition" are preferably nutritional
products
that contain sufficient types and levels of macronutrients (protein, fats and
carbohydrates)
and micronutrients to be sufficient to be a sole source of nutrition for the
animal to which
it is being administered to.
[0033] As used herein, "effective amount" is preferably an amount that
prevents a
deficiency, treats a disease or medical condition in an individual or, more
generally,
8
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
reduces symptoms, manages progression of the diseases or provides a
nutritional,
physiological, or medical benefit to the individual. A treatment can be
patient- or doctor-
related. In addition, while the terms "individual" and "patient" are often
used herein to
refer to a human, the invention is not so limited. Accordingly, the terms
"individual" and
"patient" refer to any animal, mammal or human having or at risk for a medical
condition
that can benefit from the treatment.
[0034] As used herein, "incomplete nutrition" are preferably nutritional
products that do not contain sufficient levels of macronutrients (protein,
fats and
carbohydrates) or micronutrients to be sufficient to be a sole source of
nutrition for the
animal to which it is being administered to.
[0035] As used herein, "Long term administrations" are preferably continuous
administrations for more than 6 weeks.
[0036] The term "microorganism" is meant to include the bacterium, yeast
and/or
fungi, a cell growth medium with the microorganism or a cell growth medium in
which
microorganism was cultivated.
[0037] As used herein, a "Prebiotic" is preferably a food substances that
selectively promote the growth of beneficial bacteria or inhibit the growth of
pathogenic
bacteria in the intestines. They are not inactivated in the stomach and/or
upper intestine or
absorbed in the GI tract of the person ingesting them, but they are fermented
by the
gastrointestinal microflora and/or by probiotics. Prebiotics are for example
defined by
Glenn R. Gibson and Marcel B. Roberfroid, Dietary Modulation of the Human
Colonic
Microbiota: Introducing the Concept of Prebiotics, J. Nutr. 1995 125: 1401-
1412.
[0038] As used herein, Probiotics micro-organisms (hereinafter "probiotics")
are
preferably microorganisms (alive, including semi-viable or weakened, and/or
non-
replicating), metabolites, microbial cell preparations or components of
microbial cells that
could confer health benefits on the host when administered in adequate
amounts, more
specifically, that beneficially affect a host by improving its intestinal
microbial balance,
leading to effects on the health or well-being of the host. (Salminen S,
Ouwehand A.
Benno Y. et al "Probiotics: how should they be defined" Trends Food Sci.
Technol.
1999:10 107-10). In general, it is believed that these micro-organisms inhibit
or influence
9
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
the growth and/or metabolism of pathogenic bacteria in the intestinal tract.
The probiotics
may also activate the immune function of the host. For this reason, there have
been many
different approaches to include probiotics into food products.
[0039] As used herein, "Short term administrations" are preferably continuous
administrations for less than 6 weeks.
[0040] The terms "Tolerable Upper Limit and Upper Limit (UL)" are preferably
meant to include the maximum nutrient level that will likely pose no risk of
adverse
events.
[0041] As used herein, the terms "treatment", "treat" and "to alleviate" is
preferably to both prophylactic or preventive treatment (that prevent and/or
slow the
development of a targeted pathologic condition or disorder) and curative,
therapeutic or
disease-modifying treatment, including therapeutic measures that cure, slow
down, lessen
symptoms of, and/or halt progression of a diagnosed pathologic condition or
disorder; and
treatment of patients at risk of contracting a disease or suspected to have
contracted a
disease, as well as patients who are ill or have been diagnosed as suffering
from a disease
or medical condition. The term does not necessarily imply that a subject is
treated until
total recovery. The terms "treatment" and "treat" also refer to the
maintenance and/or
promotion of health in an individual not suffering from a disease but who may
be
susceptible to the development of an unhealthy condition, such as nitrogen
imbalance or
muscle loss. The terms "treatment", "treat" and "to alleviate" are also
intended to include
the potentiation or otherwise enhancement of one or more primary prophylactic
or
therapeutic measure. The terms "treatment", "treat" and "to alleviate" are
further intended
to include the dietary management of a disease or condition or the dietary
management
for prophylaxis or prevention a disease or condition
[0042] All dosage ranges contained within this application are intended to
include
all numbers, whole or fractions, contained within said range.
[0043] As used herein, "Comensal bacteria" are those microorganisms that help
the digestion of food and acquiring of nutrients such as vitamins B and K, and
assisting
the immune system in preventing the colonization of pathogens that cause
disease by
competing with them.
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
[0044] As used herein, a "Comensal Effect" is when a microorganism, by itself,
or
aids another organism in helping the digestion of food and acquiring of
nutrients such as
vitamins B and K, and assisting the immune system in preventing the
colonization of
pathogens that cause disease by competing with them.
[0045] The compositions and methods in embodiments of the present disclosure
provide superior alternatives to current standards of care for improving oral
health. The
compositions and methods can be used to supplement beneficial bacteria in the
oropharynx of the patient. The compositions and methods can provide
competitive
inhibition through displacing pathogenic bacteria by competing for adhesion
sites and
nutrients. The compositions and methods can restore microfloral balance in the
patient's
oropharynx, esophagus, and the rest of the gastrointestinal ("GI") tract.
[0046] The compositions and methods do not need to be used in conjunction with
ventilators that can collect pathogens (e.g., reservoir) and provide a place
to attack them
wherein. Under normal circumstances, there is no place for the bacteria to be
static/colonize, etc.
[0047] The compositions and methods can utilize natural, indigenous probiotics
that reduce salivary pathogenic bacterial load in the oropharynx and
nasopharynx.
Through competitive inhibition, the natural, indigenous probiotics can offer
oral health
without killing the other bacteria or inducing antibiotic-resistance. However,
certain
probiotics can kill pathogenic bacteria and inhibit their reproduction (e.g.
1. reuteri
produce natural antiobiotics that kill pathogens). The probiotics can compete
with
receptor signaling sites that mediate systemic inflammation. As a result, the
ingested
probiotics can then confer immune and gut health benefits. An advantage of
this ingestion
can be multifold as it addresses the immune response of the patient from the
oral cavity to
systemic immune response.
[0048] The compositions and methods in alternative embodiments of the present
disclosure can reduce the use of antibiotics in a dysphagia patient, reduce
pathogenic
bacterial load in a dysphagia patient, reduce pathogenic bacterial load in the
oropharynx
of a dysphagia patient, reduce pathogenic bacterial load in the nasopharynx of
a dysphagia
patient, reduce pathogenic bacterial load in the oropharynx and nasopharynx of
a
11
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
dysphagia patient, reduce pathogenic bacterial load in dysphagia patients
(e.g. wherein the
pathogenic bacterial is AGNB), and improve the overall health and
cardiovascular of the
patient.
[0049] The compositions and methods in embodiments of the present disclosure
can utilize a therapeutically effective amount of live or inactivated
beneficial bacteria (e.g.
probiotics) as follows:
a. Delivered orally
i) Alone
(1) Liquids
(2) Semi-solids
(3) Lozenges
(a) Including lollipops
(4) Sachets
(5) Films
ii) In conjunction with
(1) Liquids
(a) Oral nutritional supplement s
(i) Premixed in
(ii) Modules to be added
(iii)Complete oral nutritional supplements ("ONS") for use as directed
by a medical professional - that contains protein, carbohydrate, fat
and micronutrients (fiber optional) sufficient for sustaining life and
other bioactive compounds such as phytochemicals, bacterial by
products, nucleotides, etc
(iv)Incomplete ONS missing one or more of the components of a
complete ONS
(v) Contains enriched levels of one or more of the components of a
complete ONS
(b) Other beverages
(i) Juices, milk, soft drinks, coffee, teas, water
(2) Solids
(i) Modules to be sprinkled on food
1. Including gravy and sauces
2. Includes semi-solids
a. Puddings, jello, jellies
(ii) Bars
(iii)Other topical compounds such as vitamin E, vitamin A, Zn, vitamin
C, nucleotides and other bioactive compounds such as
phytochemicals, bacterial by products, nucleotides, etc.
(iv)Modified consistency food products/mixes (e.g., puree)
(3) Other topical compounds (e.g., Vitamin C and Zinc)
(4) Improve oral health and/or immunity
12
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
(i) Substances that affect the binding capacity of pathogens with
receptor signaling sites that mediates local and/or systemic
inflammation
(b) Decrease pathogenic load
(i) Substance that create an unfavorable environment for the growth of
pathogens
1. Replaces or binds the essential nutrients (e.g., fuel-sugar, free-
water content) that support the growth of pathogens
2. Alters the pH
3. Generates an anti-microbial substance that inhibits pathogen
growth
iii) Thickeners
(1) Starches
(2) Gum-based
(3) Other plant extracts
(a) Bamboo shoot
(4) Proteins
b. Bacteria indigenous to the oral cavity
i) streptococcus Salivarius
ii) Lactobacillus reuteri
iii) Lactobacillus platarum 299 or 299v
c. Bacteria non-indigenous to the oral cavity
d. Prebiotics and nucleotides
e. Substances that promote non-pathogenic bacteria (i.e. like prebiotics in
the
intestine)
i) Optimizes the environment (e.g., pH, energy source availability) to favor
growth of non-pathogenic bacteria, availability of free-water
ii) Other Ingredients with desired properties in accordance with the present
invention include: CGMP which has been shown in testing to prevent binding
of pathogens and is known to be effective against Streptococcus mutans and
Streptococcus sobrinus.
[0050] The repeated consumption of the compositions in embodiments of the
present disclosure as part of daily life can improve oral health by replacing
the pathogenic
bacteria with beneficial, non-pathogenic bacteria. Oral health can also be
improved as a
result of the releasing of beneficial chemicals by the bacteria (e.g. anti-
microbials). In
addition, as the individual aspirates their saliva, the pathogenic bacterial
load will be low
and the likelihood of onset of aspiration pneumonia can be reduced.
[0051] Non-limiting examples of bacteria to be used in accordance with this
invention include one or more of. Streptococcus salivarius K12, Lactobacillus
reuteri
ATCC55730, Lactobacillus johnsonii Lal, Lactobacillus plantarum 299v,
Lactobacillus
13
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
rhamnosus GG Streptococcus thermophilus NCC 1561, Lactococcus lactis NCC2211
(Pelargon strain), and Lacteol.
[0052] Streptococcus salivarius K12, which produces produce salivaricin A and
B,
in testing has been shown to be effective against Streptococus pyogenes,
Micrococcus
luteus, Streptococcus anginosis, Eubacterium saburreum, Micromonas micros,
Moraxella,
Prevotella intermedia, and Porphyomonas gingivalis,
[0053] Lactobacillus reuteri ATCC55730, which produces reuterin, in testing
has
been shown to be effective against: Streptococcus mutans, EHEC Escherichia
coli, ETEC
Escherichia coli, Salmonella enterica,Shigella sonnei, Vibrio cholerae.
Additionally,
Lactobacillus reuteri ATCC55730 has a commensal effect on L. casei ATCC 334,
L.
johnsonii ATCC33200, L. acidophilus ATCC 4356, L. gasseri ATCC 33323,
Clostridium
difficile, Eubacterium eligens, Bifidobacterium longum var infantis,
Eubacterium biforme,
Bifidobacterium longum, Bifidobacterium catenulatum, Bacteroides vulgatus, and
Bacteroides thetaiotaomicron.
[0054] Lactobacillus johnsonii Lal, which produces H202, in testing has been
shown to be effective against: Escherichia coli (ETEC, EPEC), Salmonella
typhimurium,
Yersinia pseudotuberculosis, Helocobacter pylori, Toxin A from Clostridium
difficile,
Shigella flexneri, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter
cloacae,
Staphylococcus aureus, and Listeria monocytogenes.
[0055] Lactobacillus plantarum 299v has been shown to help prevent
colonisation
of pathogens, and aids in preventing ventilation associated pneumoniae (VAP).
Testing
has shown that LP299v is effective against: Streptococcus mutans,
Streptococcus
sobrinus, and Escherichia coli.
[0056] Lactobacillus rhamnosus GG has also been shown to help prevent
colonisation of pathogens, and aids in preventing ventilation associated
pneumoniae
(VAP). Testing has shown that Lactobacillus rhamnosus GG is effective against
Streptococcus mutans, Streptococcus sobrinus, and Escherichia coli.
[0057] Streptococcus thermophilus NCC 1561 , in testing has been shown to be
effective against Actinomyces viscosus, and Strepotcoccus sobrinus.
14
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
[0058] Lactococcus lactis NCC2211 (Pelargon strain), in testing has been shown
to be effective against Actinomyces viscosus and Strepotcoccus sobrinus.
Examples of Non-Replicating Micro-organisms include
[0059] Lacteol which acts by a mechanismof inhibition of adhesion of pathogens
(adheres to Caco 2 and HT29-MRX cells) and has been shown in testing to
prevent
adhering of Lysteria monocytogenes, ETEC Escherichia coli, EPEC Escherichia
coli,
Yersinia pseudotuberculosis, and Salmonella typhimurium. Additionally, Lacteol
has
been shown to have antimicrobial activity against: Staphylococcus aureus,
Listeria
monocytogenes, Bacillus cereus, Salmonella typhimurium, Shigella flexneri,
Escherichia
coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp.
[0060] In yet another embodiment, the present disclosure provides a method of
reducing healthcare costs. The method comprises administering to a patient at
risk of or
having oral health problems a composition comprising a therapeutically
effective amount
of a beneficial bacteria selected from the group consisting of Lactobacillus
reuteri,
Lactobacillus plantarum, streptococcus Salivarius, Streptococcus salivarius
K12,
Lactobacillus reuteri ATCC55730, Lactobacillusjohnsonii Lal, Lactobacillus
plantarum
299v, Lactobacillus rhamnosus GG Streptococcus thermophilus NCC 1561,
Lactococcus
lactis NCC2211 (Pelargon strain), and Lacteol and combinations thereof. The
reduction
in healthcare costs can be due to decreased incidences of aspiration pneumonia
or general
pneumonia that may not be differentially diagnosed. Alternatively, the
reduction in
healthcare costs can be due to a reduced treatment of secondary infections
and/or
prevention of a downward spiral in health. This can include, for example, loss
of
functionality, frailty, disability and death.
[0061] More specifically, the health economic benefits can be as follows:
= Reduce hospitalizations, rehospitalizations, sub-acute care, transitional
care, home
health care, outpatient care, physician office visits and follow-up care
o Reduce medical costs to the health care system for aspiration pneumonia
and general pneumonia that may not be differentially diagnosed
= Reduced necessary specialized care
o Reduce medical costs to the health care system for dehydration, use of
artificial ventilation, emergency room visits, pulmonary rehabilitation and
physical therapy post-artificial ventilation, nosocomial infections and
recurrence (e.g., urinary tract infections, C. difficile associated diarrhea)
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
= Reduced need for antibiotics
o Fewer superbugs floating around (antibiotic resistant bacteria)
^ Methicillin-resistant Staphylococcus aureus (MRSA)
^ C. difficile
= Saved costs for better overall health
o Cardiovascular, diabetes, metabolic syndrome
o Avoid the downward spiral in health that can lead to loss of functionality,
frailty, increased risk of illness injury & death, disability, increased
(formal
& informal) caregiver burden, and institutionalization
= Reduced costs of dental care or physician office visits
EXAMPLES
[0062] By way of example and not limitation, the following examples are
illustrative of various embodiments of the present disclosure.
EXAMPLE 1
[0063] Table 1 lists components for a complete feeding product (powder or
liquid)
appropriate for nutritional supplementation of patients with or at risk of
dysphagia, those
at high risk of aspiration, at high risk of pneumonia, and at risk of poor
oral health.
Table 1
Ingredient Amount Function
Probiotic Strain > 10,000 CFU (powder or Bacteriotherapy
in straw, cap or another (displacement of
delivery mechanism) pathogenic bacteria)
Caseinate 75 (20% of energy) High quality protein
Canola oil 50 g (30% of energy) Fatty acid source and
energy
Maltodextrin 188 g (50% of energy) Carbohydrate and
energy source
Yeast extract 2.5 RNA/nucleotide source
Vitamin premix
Mineral premix
Emulsifier
water
Optional ingredients As listed elsewhere
16
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
EXAMPLE 2
[0064] Compositions having thickeners that are appropriate for nutritional
supplementation of patients with or at risk of dysphagia, those at high risk
of aspiration, at
high risk of pneumonia, and at risk of poor oral health can include components
of Table 2.
The thickeners can be starches, gums or other plant or animal based
thickeners.
Table 2
Ingredient Amount Function
Probiotic Strain > 10,000 CFU (powder or Bacteriotherapy
in straw, cap or another (displacement of
delivery mechanism) pathogenic bacteria)
Thickener Increases viscosity for
ease and safety of
swallowing
Optional nutrient: Enriches the diet in
(e.g., high quality essential or beneficial
protein) nutrients
EXAMPLE 3
[0065] Modular powders or liquid supplements (e.g., protein) appropriate for
nutritional supplementation of patients with or at risk of dysphagia, those at
high risk of
aspiration, at high risk of pneumonia, and at risk of poor oral health can
include
components of Table 3.
Table 3
Ingredient Amount Function
Probiotic Strain > 10,000 CFU (powder or Bacteriotherapy
in straw, cap or another (displacement of
delivery mechanism) pathogenic bacteria)
17
CA 02747231 2011-06-15
WO 2010/077795 PCT/US2009/067809
Nutrient (e.g., high Enriches the diet in
quality protein) essential or beneficial
nutrients
[0066] It should be understood that various changes and modifications to the
presently preferred embodiments described herein will be apparent to those
skilled in the
art. Such changes and modifications can be made without departing from the
spirit and
scope of the present subject matter and without diminishing its intended
advantages. It is
therefore intended that such changes and modifications be covered by the
appended
claims.
18
