COMPOSITIONS DE SUPPRESSION DE L`APPETIT ET METHODES CONNEXES

APPETITE SUPPRESSANT COMPOSITIONS AND METHODS THEREOF

Abrégé français

Selon divers modes de réalisation, une composition de suppression de lappétit comprend au moins un ingrédient actif anorexigène; une substance nutritive, un agent dapport de médicament régulé et/ou un cofacteur; et, facultativement, un excipient. Lingrédient actif anorexigène peut comprendre lun ou lautre de phentermine, phendimétrazine, diéthylpropion, naltrexone et bupropion. Lagent dapport de médicament régulé peut comprendre un cellulosique. Le cofacteur peut comprendre un sel de chrome ou sélénium. Selon divers modes de réalisation, les compositions dans la présente sont fournies dans une forme de dosage de capsule orale pour ladministration, dans le tractus gastro-intestinal, de lingrédient actif anorexigène. Il est décrit une méthode de suppression de lappétit chez des individus qui en ont besoin.

Abrégé anglais

In various embodiments an appetite suppressant composition comprises at least one anorectic active ingredient (AAI); at least one of a nutritive substance, a controlled drug delivery agent (CDRA), and a cofactor; and optionally, an excipient. The AIA may comprise any one of phentermine, phendimetrazine, diethylpropion, naltrexone, and bupropion. The CDRA may comprise a cellulosic. The cofactor may comprise a chromium or selenium salt. In various embodiments, the compositions herein are provided in an oral capsule dosage form for GI-tract administration of the AAI. A method of suppressing appetite in individuals in need thereof are described.

Revendications

CLAIMS
1. An appetite suppressant composition consisting essentially of:
from 4.0 wt.% to 16.0 wt.% phentermine hydrochloride;
from 40.0 wt.% to 46.0 wt% hydroxypropyl methyl cellulose;
from 40.0 wt.% to 51.0 wt% bovine collagen; and
from 0.05 wt.% to 0.10 wt.% chromium picolinate.
2. A pharmaceutical dosage form for oral administration comprising: a capsule;
and the appetite
suppressant composition of claim 1 enclosed therein.
3. Use of the appetite suppressant composition as defined in claim 1 for
suppressing appetite in an
individual in need thereof.
4. Use of the appetite suppressant composition as defined in claim 1 in the
manufacture of a
medicament for suppressing appetite in an individual in need thereof.
5. The use of claim 3 or 4, wherein the use comprises up to 75 mg per day of
the phentermine
hydrochloride.
6. The use of any one of claims 3 to 5, wherein the individual in need thereof
is diagnosed
overweight and obese.
7. An appetite suppressant dosage form consisting essentially of:
250 mg to 350 mg of the appetite suppressant composition of claim 1 as a loose
powder;
and
a dissolvable capsule enclosing said appetite suppressant composition.
8. Use of the appetite suppressant dosage form of claim 7 for suppressing
appetite in an individual
in need thereof.

9. Use of the appetite suppressant dosage form of claim 7 in the manufacture
of a medicament for
suppressing appetite in an individual in need thereof.
10. Use of the pharmaceutical dosage form of claim 2 for suppressing appetite
in an individual in
need thereof.
11. Use of the pharmaceutical dosage form of claim 2 in the manufacture of a
medicament for
suppressing appetite in an individual in need thereof.
3 1

Description

Docket No. 58872.00303
TITLE: APPETITE SUPPRESSANT COMPOSITIONS AND METHODS
THEREOF
INVENTOR: SUZANNE BENTZ
ASSIGNEE: RED MOUNTAIN HOLDINGS, LLC
FIELD
[0001] This disclosure generally relates to pharmaceutical compositions,
and more
specifically, to orally administered appetite suppressant compositions and
methods thereof
BACKGROUND
[0002] Individuals from wealthy industrialized countries are increasingly
obsessed by
health and beauty. These individuals help fuel a multi-billion dollar market
for OTC diet
products, medically assisted weight loss such as prescription drugs and
bariatric surgery,
cosmetic surgery and cosmetics and anti-aging treatments. Some individuals
find difficulty
maintaining proper diet and exercise regiment, and are often turning to
formulations and
programs promoting rapid weight loss and body sculpting.
[0003] In the United States, an alarming percentage of the population is
obese, yet the
requirements for gastric bypass surgery remains that one be medically
diagnosed obese.
Others may find the surgery to not be worth the risk.
[0004] In view of these and other personal and physiological challenges
in achieving and
managing a healthy weight, new weight management compositions and health
programs are
still needed.
SUMMARY
[0005] In various embodiments, new appetite suppressant compositions are
described. In
various embodiments, appetite suppressant compositions are compounded in a
dosage form
for oral administration.
[0006] In various embodiments, new appetite suppressant compositions
comprise an
immediate release oral dosage form or a controlled release oral dosage form.
[0007] In various embodiments, new appetite suppressant compositions
comprise an
immediate release capsule oral dosage form.
[0008] In various embodiments, new appetite suppressant compositions
comprise a
controlled release capsule oral dosage form.
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[0009] In various embodiments, an appetite suppressant composition comprises
at least one
anorectic active ingredient; at least one of a nutritive substance, a
controlled drug release agent,
and a cofactor; and optionally, an excipient.
[0010] In various embodiments, the composition as defined herein, wherein
the anorectic
active ingredient is selected from the group consisting of diethylpropion,
amphetamine,
benfluorex, bupropion, butanolide, caffeine, cathine, cetilistat, clobenzorex,
D-fenfluramine,
racemic-fenfluramine, ephedrine, etilamfetamine, exenatide, FG-7142 (diazepine
inverse
agonist), higenamine, liraglutide, lorcaserin, mazindol, mefenorex, metformin,
methamphetamine, naltrexone, nicotine, orlistat, phenmetrazine,
phendimetrazine,
phentermine, phenylpropanolamine, pramlinatide, pseudoephedrine, pyroglutamyl-
histidyl-
glycine, rimonabant, semaglutide, sibutiamine, topiramate, yohimbine, pro-
drugs thereof,
pharmaceutically acceptable salts thereof, and mixtures thereof.
[0011] In various embodiments, a pharmaceutical dosage form for oral
administration
comprises a capsule; and an appetite suppressant composition comprising at
least one anorectic
active ingredient; at least one of a nutritive substance, a controlled drug
release agent, and a
cofactor; and optionally, an excipient enclosed within the capsule.
[0012] In various embodiments, the nutritive substance is selected from
the group
consisting of a dried Spirulina algal species biomass powder, a dried
Chlorella algal species
biomass powder, a hydrolyzed powdered bovine or fish collagen, a bovine or
porcine gelatin
powder, egg albumin powder, calcium caseinate powder, powdered milk protein
concentrate,
whey protein isolate powder, yellow pea protein isolate, and mixtures thereof.
[0013] In various embodiments, the controlled drug release agent is
selected from the group
consisting of agar, agarose, albumin, alginate, casein, chitin, chondroitin,
dextrin, fibroin,
fucoidan, galactan, gellan, guar, scleroglucan, pullulan, xyloglucan, pectin,
xanthan, psyllium,
silica gel, fumed silica, magnesium aluminum silicate, clay, bentonite,
hectorite, mesoporous
silica, cellulose, cellulose acetate, hyaluronan, elastin-like polypeptides,
f3-cyclodextrin,
collagen, gelatin, chitosan, carrageenan, polylactic acid, polyglycolic acid,
poly(lactic-glycolic
acid) (PLGA), poly(2-hydroxyethyl methacrylate), poly(2-hydroxypropyl
methacrylate),
poly(acrylic acid), carboxymethyl cellulose, carboxyethyl cellulose,
hydroxyethyl cellulose,
hydrophobically-modified hydroxyethyl cellulose, hydroxypropyl cellulose,
hydroxypropyl
methyl cellulose, methyl cellulose, ethyl cellulose, microcrystalline
cellulose, nitrocellulose,
polyvinyl alcohol, polyvinylpyrrolidone, polyvinylmethacrylate, carboxyvinyl
polymers,
polyvinylacetate, polyvinyl co-polymers, starch, modified starches, and
mixtures thereof.
2
Date Recue/Date Received 2022-04-12

[0014] In various embodiments, the cofactor is selected from the group
consisting of
calcium acetate, calcium ascorbate, calcium citrate, calcium gluconate,
calcium nicotinate,
calcium picolinate, chromium acetate, chromium ascorbate, chromium citrate,
chromium
gluconate, chromium nicotinate, chromium picolinate, copper acetate, copper
ascorbate,
copper citrate, copper gluconate, copper nicotinate, copper picolinate,
magnesium acetate,
magnesium ascorbate, magnesium citrate, magnesium gluconate, magnesium
nicotinate,
magnesium picolinate, manganese acetate, manganese ascorbate, manganese
citrate,
manganese gluconate, manganese nicotinate, manganese picolinate, potassium
acetate,
potassium ascorbate, potassium citrate, potassium gluconate, potassium
nicotinate, potassium
picolinate, selenium acetate, selenium ascorbate, selenium citrate, selenium
gluconate,
selenium nicotinate, selenium picolinate, zinc acetate, zinc ascorbate, zinc
citrate, zinc
gluconate, zinc nicotinate, zinc picolinate, and mixtures thereof.
[0015] In various embodiments, the anorectic active ingredient comprises
phentermine,
phendimetrazine, or diethylpropion, the nutritive substance comprises a
protein source, the
controlled drug release agent comprises a cellulosic, and the cofactor
comprises calcium
picolinate, chromium picolinate, copper picolinate, magnesium picolinate,
manganese
picolinate, selenium picolinate, or zinc picolinate.
[0016] In various embodiments, the cellulosic controlled drug release
agent comprises
hydroxypropyl methyl cellulose.
[0017] In various embodiments, the nutritive substance is a protein source
comprising
hydrolyzed powdered bovine or fish collagen.
[0018] In various embodiments, the cofactor comprises chromium
picolinate.
[0019] In various embodiments, a method of suppressing appetite is
disclosed. The method
comprises orally administering to the individual in need thereof a
therapeutically effective
amount of an appetite suppressant composition comprising at least one
anorectic active
ingredient; at least one of a nutritive substance, a controlled drug release
agent, and a cofactor;
and optionally, an excipient, wherein the anorectic active ingredient is
selected from the group
consisting of phentermine, phendimetrazine, diethylpropion, naltrexone,
bupropion, and
mixtures thereof.
[0020] In various embodiments of the method, the appetite suppressant
composition
comprises each of a nutritive substance, a controlled drug release agent, and
a cofactor, wherein
the nutritive substance comprises a protein source.
[0021] In various embodiments of the method, the therapeutically
effective amount
comprises orally administering up to about 75 mg per day of phentermine.
3
Date Recue/Date Received 2022-04-12

[0022] In various embodiments of the method, the protein source comprises
hydrolyzed
powdered bovine or fish collagen, the controlled drug release agent comprises
a cellulosic, and
the cofactor comprises calcium picolinate, chromium picolinate, copper
picolinate, magnesium
picolinate, manganese picolinate, selenium picolinate, or zinc picolinate.
[0023] In various embodiments of the method, the appetite suppressant
composition
comprises each of a nutritive substance and a cofactor, and no controlled drug
release agent,
wherein the nutritive substance comprises a protein source.
[0024] In various embodiments of the method, the therapeutically
effective amount
comprises orally administering up to about 210 mg per day of phendimetrazine.
[0025] In various embodiments of the method, the therapeutically effective
amount
comprises orally administering up to about 150 mg per day of diethylpropion.
[0026] In various embodiments of the method, the protein source comprises
hydrolyzed
powdered bovine or fish collagen, and the cofactor comprises calcium
picolinate, chromium
picolinate, copper picolinate, magnesium picolinate, manganese picolinate,
selenium
picolinate, or zinc picolinate.
[0027] In various embodiments of the method, the cofactor is chromium
picolinate.
[0028] In various embodiments of the method, the individual in need
thereof is diagnosed
overweight and obese.
DETAILED DESCRIPTION
[0029] The detailed description of exemplary embodiments refers to the
accompanying
drawings, which show exemplary embodiments by way of illustration and best
mode. While
these exemplary embodiments are described in enough detail to enable those
skilled in the art
to practice the invention, other embodiments may be realized, and logical,
chemical, and
mechanical changes may be made without departing from the spirit and scope of
the inventions.
Thus, the detailed description is presented for purposes of illustration only
and not of limitation.
For example, unless otherwise noted, the steps recited in any of the method or
process
descriptions may be executed in any order and are not necessarily limited to
the order presented.
Furthermore, any reference to singular includes plural embodiments, and any
reference to more
than one component or step may include a singular embodiment or step. Also,
any reference
to attached, fixed, connected or the like may include permanent, removable,
temporary, partial,
full and/or any other possible attachment option. Additionally, any reference
to without contact
(or similar phrases) may also include reduced contact or minimal contact.
4
Date Recue/Date Received 2022-04-12

Docket No. 58872.00303
[0030] Appetite suppressant compositions comprising an appetite suppressant
pharmaceutical active, (e.g., an anorectic active ingredient, or "AAI") are
described. In
various embodiments, an appetite suppressant composition in accordance with
the present
disclosure comprises: at least one AAI; and any one of or combination of
nutritive
substances, controlled drug release agents ("CDRAs"), cofactors, excipients,
and/or fillers.
[0031] Definitions
[0032] As used herein, the tenns "anorectic," or "appetite suppressant,"
or "anorectic
pharmaceutical active," or "anorectic AI" (Al = active ingredient), or most
simply, the
acronym "AAI," refer to any chemical substance now known or yet to be
discovered that is
capable of suppressing the feeling of hunger and/or the craving for food in an
individual,
regardless if the chemical substance is currently registered with a regulatory
agency, such as
the United States Food & Drug Administration (FDA) or not. For example, an AAI
for use
herein may comprise a chemical newly synthesized in a research laboratory, or
a natural
product just having been isolated, and not yet presented to any regulatory
agency which
might never be registered. Included in the broad class of known AAIs are the
very familiar
alkaloids caffeine and nicotine. Some AAIs mentioned for use herein may have
additional
pharmacological effects besides appetite suppression, e.g., anti-obesity, or
might indirectly
provide appetite suppression as a consequence or artifact of a primary
pharmacological effect
(e.g., glucose production controlled by diabetes medications). Current
regulatory status,
including withdrawal from registered use, is not considered since prior
regulatory issues
could have been related to physical dosage forms or administration routes and
practices that
are not within the scope of the present disclosure.
[0033] In various embodiments, AAIs that find use in the present appetite
suppressant
compositions in accordance with the present disclosure include, but are not
limited to,
amfepramone (diethylpropion), amphetamine and analogs thereof, benfluorex,
bupropion,
butanolide, caffeine, cathine, cetilistat, clobenzorex, dexfenfluramine (D-
fenfluramine),
ephedrine, etilamfetamine, exenatide,
racemic-fenfluramine, FG-7142, higenamine,
liraglutide, lorcaserin, mazindol, mefenorex, metformin, methamphetamine and
analogs
thereof, naltrexone, nicotine, orlistat, phenmetrazine, phendimetrazine,
phentermine,
phenylpropanolamine, pramlinatide, pseudoephedrine, pyroglutamyl-histidyl-
glycine,
rimonabant, semaglutide, sibutramine, topiramate, yohimbine, pro-drugs
thereof,
pharmaceutically acceptable salts thereof, and combinations thereof. Any of
these AAIs may
be commercially obtained and pharmaceutically administered as a salt, e.g., a
hydrochloride
salt or a tartrate salt. For simplicity, reference is made to the active
without the -HC1 or -
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Docket No. 58872.00303
tartrate suffix designation. In various embodiments, whole plant or fungal
material (e.g.,
ephedra (Ma Huang), bitter melon, maitake, purslane, tea), or any plant, root,
bark, tree or
flower extract, may be used as an AAI herein, recognizing that the appetite
suppressant effect
may be more of any one of a homeopathic effect, prophylactic effect, sensory
effect, placebo
effect, or psychological effect effect rather than a recognizable
physiological effect
describable by biochemical pathways.
[0034] AAIs
for use herein may comprise drugs characterizable or otherwise known as
stimulants, antidiabetic agents, glucose regulating agents, thyroid hormones,
thyroid drugs,
parathyroid drugs, vitamins, antihyperlipidemic agents, cardiac drugs,
respiratory drugs, nasal
decongestants, gastrointestinal drugs, amphetamines, anorexiants,
antirheumatic agents, anti-
gout agents, migraine drugs, sedatives, hypnotics, antianxiety drugs,
anticonvulsants,
antidepressants, antipsychotic agents, psychotherapeutic drugs,
antimicrobials, antifungals,
sulfonamides, antimalaria drugs, antituberculotic drugs, amebicides, antiviral
agents, anti-
infectives, leprostatics, antihelmintics, antihistamines, antimetabolites,
anticholinergics,
steroidal anti-inflammatories, anesthetics, antiplatelet drugs, NSAIDs, ace
inhibitors, calcium
channel blockers, alpha-blockers, muscle relaxers, antihypertensives,
vasodilators, diuretics,
antiemetics, sex hormones, pituitary hormones, analgesics, uterine hormones,
and adrenal
steroid inhibitors. Such drugs might have a primary known physiological use,
like a
stimulant, but also a secondary appetite suppressant effect.
[0035] As used herein, the term "cofactor" refers to a non-protein
substance that
associates with an enzyme in order for the enzyme to function in vivo. In
general, enzyme
cofactors include both inorganic ions, such as metal cations, and organic
molecules including
a number of vitamins and nucleotides. For use herein, metal cation cofactors
include, but are
not limited to, 13a2, Ca', Ce31", Cd", Co', Co31, Cr' , Cr, Cr', Cu', Cu',
Fe", Fe', K+1,
La', mg2+, mn+2, mo21, mo3+7 Mo4t, Mo5,NO', Ni2+, se2+, zn2+, iron-sulfur
clusters
(e.g., Fe2S2 and Fe4S202 iron-sulfur-oxygen cluster), and combinations
thereof. The anion
for any of these and other metal cation cofactors can be any inorganic or
organic anion, such
as a halide, carbonate, phosphate, pyrophosphate, tripolyphosphate, sulfate,
sulfide, or a
carboxylate (nicotinic acid, isonicotinic acid, acetate, etc.), or a
bidentate, tridentate,
tetradentate, or other chelating or coordination agent, such as ascorbic acid,
citric acid,
dimercaprol, gluconic acid, nicotinamide, oxalic acid, 1,10-phenanthroline,
picolinic acid,
2-(2 ' -pyridyl)imidazole, 2-(2'-pyridyl)benzimidazole,
ethylenediamine,
ethylenediaminetetraacetic acid (EDTA), acetylacetonate, and combinations
thereof. For oral
administration and GI tract bioavailability, it is more common to use an
organic anion (e.g,
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acetate, nicotinate, etc.) or a bidentate, tridentate, tetradentate, or other
complexed metal
cation (e.g., gluconate, citrate, picolinate, etc.) for a cofactor rather than
an inorganic anion
(e.g., chloride, sulfate, etc.) to provide the metal cation active portion of
the cofactor. In some
instances, both the cation and the anion can be active physiological agents,
(e.g., nicotinate
salts, since nicotinic acid is niacin, or vitamin B3). Further, in certain
complexes, one or
more coordination compounds and inorganic anions might associate with a single
metal
cation, (e.g., bis-phenanthroline Cr(III) complexes can include two chlorine
atoms bonded to
the chromium, and C1 as a counterion to the 1+ charged complex). In specific
embodiments,
cofactors for use in the compositions of the present disclosure include
calcium acetate,
calcium ascorbate, calcium citrate, calcium gluconate, calcium nicotinate,
calcium picolinate,
chromium acetate, chromium ascorbate, chromium citrate, chromium gluconate,
chromium
nicotinate, chromium picolinate, copper acetate, copper ascorbate, copper
citrate, copper
gluconate, copper nicotinate, copper picolinate, magnesium acetate, magnesium
ascorbate,
magnesium citrate, magnesium gluconate, magnesium nicotinate, magnesium
picolinate,
manganese acetate, manganese ascorbate, manganese citrate, manganese
gluconate,
manganese nicotinate, manganese picolinate, potassium acetate, potassium
ascorbate,
potassium citrate, potassium gluconate, potassium nicotinate, potassium
picolinate, selenium
acetate, selenium ascorbate, selenium citrate, selenium gluconate, selenium
nicotinate,
selenium picolinate, zinc acetate, zinc ascorbate, zinc citrate, zinc
gluconate, zinc nicotinate,
zinc picolinate, and mixtures thereof.
[0036] For use herein, organic cofactors include, but are not limited to,
vitamins A, C,
B1 , B2, B3, B6, B12, H and K, thiamine pyrophosphate, NADH, NAD+, NADP+, FAD,
FADH, pyridoxal phosphate, methylcobalamine, cobalamine, biotin, coenzymes A,
B, M and
Q10 (ubiquinone), folic acid, tetrahydrofolic acid, menaquinone, ascorbic
acid, flavin
mononucleotide, coenzyme F420, adenosine 5'-monophosphate, ADP, ATP, cytidine
triphosphate, glutathione, lipoamide, 0-carotene, (6R)-5,10-
methylenetetrahydrofolate, (6R)-
5,10-methylenetetrahydrofolic acid, (68)-5,6,7,8-tetrahydrofolate, (68)-
5,6,7,8-tetrahydro folic
acid, (R)-lipoate, (R)-lipoic acid, 1,4 benzoquinone, 3'-hydroxyechinenone
5,6,7,8-
tetrahydropteridine, 5-hydroxy-benzimidazolylcob(Damide, 5-hydroxy-
benzimidazolyl-
.. cob(I)amide, 7-dimethy1-8-(1-D-ribityl)lumazine, 6,7-dimethy1-8-(1-D-
ribityplumazine, 6-
decylubiquinone, 6-hydroxy-FAD, myo-inositol hexalcisphosphate, S-adenosyl-L-
homocysteine, S-adenosyl-L-methionine zwitterion, S-adenosyl-L-methionine
zwitterion, L-
ascorbate, L-ascorbic acid, ammonium cation (NH4'), bacillithiol, biotinate,
bis(molybdopterin)tungsten, chlorophyll a, chlorophyll b, cobamamide, corrin,
corrinoid,
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decylplastoquinone, dehydro-D-arabinono-1,4-lactone,
dihydrogen vanadate,
dihydrolipoamide, dipyrromethene, dipyrromethene, divinyl chlorophyll a,
divinyl
chlorophyll b, echinenone, Fe-coproporphyrin III, ferriheme a, ferroheme b,
ferroheme
cmethanofuran, molybdopterin, various nucleotide sugars, 3' -phosphoadenosine-
5'-
phosphosulfate, quinone, pyrroloquinoline quinone, tetrahydrobiopterin,
tetrahydromethylbioterin, prodrugs thereof, pharmaceutically acceptable salts
thereof, and
combinations thereof.
[0037] As
used herein, the term "prodrug" refers to an AM that is prepared in an
inactive
form that is converted to an active form within the body or cells thereof by
the action of
endogenous enzymes or other chemicals and/or conditions. In various
embodiments, a
prodrug-AAI is compounded into a loose powder composition and loaded into
capsules for
oral administration, whereby the prodrug-AAI is converted to the active AAI in
the GI tract
of the individual.
[0038] As
used herein, the term "controlled drug release agent" (or more simply, the
acronym "CDRA"), refers to an organic substance capable of agglomerating
around an AM
so as to slow down the bioavailability of the AAI in the GI tract. In various
embodiments, an
AAI may be intimately mixed with a CDRA in a powder composition for capsule
delivery.
When the capsule dissolves in the stomach, the CDRA swells with water,
physically trapping
the AAI (and other active ingredients) until the GI tract, e.g., catalyzed by
acidity and
temperature in the gut, can break down the CDRA. In various embodiments, CDRAs
for use
herein comprise certain particle sizes, and in some instances, nanoparticles.
In various
embodiments, CDRAs for use herein comprise natural, semisynthetic and
synthetic
hydrophilic polymers capable of gelling and/or swelling. In various
embodiments, CDRAs
for use herein comprise hydrogel materials, also known as polymer hydrogels or
PHGs.
CDRAs for biological applications, such as herein, are generally
polysaccharides or
polypeptides. Combinations of hydrogels may be used to create "core-shell"
composite
hydrogels. Distinction is made between a CDRA for use to slow down active drug
release and
a disintegrant for use in speeding up drug release, even though in a formal
sense, speeding up
drug active delivery is still a form of "controlling" drug release. Attempt is
made herein to
categorize disintegrants with "excipients" and to keep CDRAs in a separate
category of
ingredients.
[0039]
CDRAs for use herein include, but are not limited to, agar, agarose, albumin,
alginate, casein, chitin, chondroitin, dextrin, fibroin, fucoidans, galactans,
gellan, guar,
scleroglucan, pullulan, xyloglucan, pectin, xanthan, psyllium, silica gel,
fumed silica,
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Docket No. 58872.00303
magnesium aluminum silicates, clay, bentonite, hectorite, mesoporous silica,
cellulose,
cellulose acetate, hyaluronan, various elastin-like polypeptides, p-
cyclodextrin, collagen,
gelatin, chitosan, carrageenan, polylactic acid, polyglycolic acid,
poly(lactic-glycolic acid)
(PLGA), poly(2-hydroxyethyl methacrylate), poly(2-hydroxypropyl methacrylate),
poly(acrylic acid), carboxymethyl cellulose, carboxyethyl cellulose,
hydroxyethyl cellulose,
hydrophobically-modified hydroxyethyl cellulose, hydroxypropyl cellulose,
hydroxypropyl
methyl cellulose, methyl cellulose, ethyl cellulose, microcrystalline
cellulose, nitrocellulose,
polyvinyl alcohol, polyvinylpyrrolidone, polyvinylmethacrylate, carboxyvinyl
polymers,
polyvinylacetate, polyvinyl co-polymers, various starches, modified starches,
and
combinations thereof. See, S.M. Fijul Kabir, et al., "Cellulose-based hydrogel
materials:
chemistry, properties and their prospective applications," Prog. Biomater.,7,
153-174 (2018).
[0040] As used herein, the term "immediate release" refers to a
pharmaceutical dosage
form designed to fall apart, dissolve, or otherwise disintegrate as quickly as
possible.
Typically, a dosage form for immediate release will be an oral dosage form,
such as a tablet
for sublingual drug administration or a capsule for swallowing with subsequent
GI drug
delivery. Capsule dosage forms may be designed for immediate drug release by
changes to
either the capsule shell, or the powder fill composition, or both. For
example, hard capsule
shells may be laser-drilled with holes that allow entry of water in the gut.
In other examples,
one or more disintegrating agents (called "disintegrants") may be added into
the powder fill
composition of a capsule, or into the capsule shell itself. In various
embodiments, immediate
release may also be coupled with increased GI absorption, and in those
instances an intestinal
permeation enhancer may be included in an immediate release composition so
that there is
not only rapid dissolution of the capsule, there is also rapid intestinal
absorption. In various
embodiments, a standard gel cap or powder filled hard gelatin capsule may
provide
immediate release in the gut simply in response to physiological conditions of
heat and acid
in the stomach, sufficiently capable of dissolving a gelatin shell in due
course. Immediate
release tends to be the opposite of controlled release or sustained release.
[0041] As used herein, the term "nutritive" refers to any substance
providing caloric or
other nutritional value to an individual, including any substances from the
classic food groups
of protein, carbohydrate, and fat. A nutritive for purposes herein may also
include nutritive
fiber, but a distinction will be made between nutritive fiber and fibrous
materials that swell
into hydrogels for controlled drug release purposes, such as cellulosic
materials. In other
words, a cellulosic in an appetite suppressant composition herein is likely
present in the
composition for sustained AAI release purposes rather than for supplying
digestive fiber.
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Another example is psyllium, a well-known digestive fiber, but a material that
also acts as a
CRDA because of its ability to swell in the gut and occlude other materials.
In various
embodiments, a nutritive may comprise a nutritive filler. Said another way, a
nutritive such as
a protein powder may be used in "quantity sufficient" (q.s.) to fill in the
remainder of a
composition totally 100 wt.%.
[0042] As used herein, the term "protein source" refers to an organic
substance or
mixture that provides a moderate to a high level of protein, shorter chain
peptides, and/or
amino acids (e.g., at least about 60 wt.% peptide materials) based on the
total weight of the
protein material. In various embodiments, a protein source may be similar if
not identical to
substances used in protein shakes in the health and fitness industry, and may
be animal or
plant derived, including aquatic plant. In various embodiments, a protein
source for use
herein may be hydrolyzed so that it can be intestinally absorbed more easily
than the parent
protein prior to hydrolysis. Protein sources for use herein include, but are
not limited to,
whey, casein, lectin, collagen, egg protein, pea protein, hemp protein, brown
rice protein,
alfalfa, chia, flax, artichoke, quinoa, a Spirulina algal species, a Chlorella
algal species, a
Schizochytrium algal species, a Laminaria algal species, an Ulva algal
species, an
Arthrospira algal species, a Porphyridium algal species, a Haematococcus algal
species, and
combinations thereof. For any of the plant and animal sources of protein, the
raw animal or
plant material or isolated protein may be left natural or hydrolyzed, and then
dried into a
powder. For the algal species, the protein source may comprise the algal
biomass itself (e.g.,
plant matter simply squeezed out, dried or spray dried, and powdered) or the
protein source
may be isolated and/or hydrolyzed proteins extracted from the algal sources.
See, S. Bleakley,
et al., "Algal Proteins: Extraction, Application, and Challenges Concerning
Production,"
Foods, 6(5), 33 (2017).
[0043] As used herein, the term "filler" refers to non-nutritive materials
that may be
added in quantity sufficient to complete a formula to "100%" total. In various
embodiments,
appetite suppressant compositions comprise a number of pharmacologically
active
substances, such as AAIs, nutritive substances, CRDAs, and cofactors, with the
remainder
comprising inert filler. In other embodiments, compositions herein comprise
sufficient
nutritive substances, like protein sources, such that inert fillers for weight
and bulk are not
needed. Fillers increase weight, but typically do not contribute to any
pharmacological effect.
Pharmaceutically acceptable inert fillers are known to the pharmaceutical
arts, and include
such substances as monosaccharides and disaccharides, (mannitol, lactose,
dextrose)
carbonates (calcium carbonate), phosphates, (calcium phosphate), and sulfates
(calcium
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sulfate). For an exhaustive listing of pharmaceutically acceptable fillers,
see "Handbook of
Pharmaceutical Excipients, 6th Edition, R. C Rowe, et al., editors,
Pharmaceutical Press,
London, 2009.
[0044] As used herein, the term "excipient" refers to additional
functional ingredients in
an appetite suppressant composition, and thus distinct from inert filler.
Excipient refers to
those ingredients that although functional, play a minor role in the
composition. These
ingredients typically include disintegrants, colors, flavorants, sweenteners,
and preservatives.
[0045] As used herein, the term "composition" takes on the ordinary
meaning in
formulation chemistry as a combination of ingredients. In various embodiments,
a
composition is designed to adopt a particular physical form, or at least be
amenable to
physical change into a desired physical form, which may be the dosage form for
a particular
treatment regimen. Typically, a composition is made homogeneous by mixing or
blending,
although not all liquid compositions are colorless and transparent and not all
powder
compositions are white and perfectly granular. Compositions comprising an
emulsion,
dispersion or suspension may be homogeneous because the droplets or particles
are evenly
spread in a carrier. So, for example, a composition herein may be in the form
of a thin liquid
(having a viscosity at or near that of water), a viscous liquid (having a
liquid of viscosity
greater than water), a paste, a cream, a jelly, a gel, or a powder.
Ingredients for a
composition herein arc generally shown "as added," meaning there is a
possibility for one or
more chemical reactions between ingredients once the ingredients are mixed
together, such as
into a common carrier. One skilled in the art of formulation chemistry can
recognize whether
ingredients might react in a mixture. These reactions can include
neutralization (e.g., between
acid and alkali ingredients), mixed micelle formation (mixed surfactants in
liquid systems) or
other encapsulation phenomena, hydrolysis, and so forth. In various
embodiments, a
composition herein comprises a blended powder that can be packed into capsules
for oral
administration. In some instances, a composition may take into consideration
an outer
encasing when that material is also included in the administration of the
composition to an
individual. For example, a gelatin capsule may be included in the listing of
ingredients for a
composition, or perhaps just the ingredients of the contents of the capsule
may be listed. In
various embodiments, ingredients in a composition are listed in "weight
percent," (i.e.,
"wt.%"), based on the total weight of the composition. For example, 100
milligrams of a
composition comprising 40 mg A and 60 mg B may be recited as "40 wt.% A and 60
wt.% B,
based on the total weight of the composition," which necessarily totals to
"100 wt.%." The
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actual weight amounts, (e.g., milligrams or grams) generally refers to amounts
added for a
particular batch size, (e.g., a batch size of powder usable to fill 100
capsules).
[0046] As used herein, the term "dosage form" takes on its ordinary
meaning in the
pharmaceutical arts as the physical form of a composition designed for a
particular
administration route. For example, dosage forms include, but are not limited
to, injectables,
infusible liquids, nasal sprays, nasal gels, topicals such as transdermal
creams, ointments and
patches, loose powders, tablets, sublingual tabs, capsules, lozenges, syrups,
vapors, and so
forth. In various embodiments, compositions of interest herein comprise
powders, and the
dosage form comprises a capsule comprising the powdered composition encased or
"encapsulated" in the capsule or a table comprising the powdered composition
compressed
into a shape for oral swallowing or sublingual dissolution.
[0047] As used herein, the term "capsule" generally refers to a one or
two piece enclosure
for a loose powder, which can be swallowed for oral administration of the
powder contents of
the capsule, or a soft-shell for a liquid composition, otherwise known as a
"gel cap"). In
general, "soft" capsules for liquids are one piece, whereas "hard" capsules
for powders are
two piece. In some instances, the capsule is said to "encapsulate" the powder
contained
therein, which can be confusing because the term "encapsulation" is often
used, perhaps more
correctly used to describe a microscale or nanoscale phenomenon rather than
describing
something macroscopic like a drug dosage form. In various embodiments,
capsules for use
.. herein are hard, stable two piece shells, or enclosures, capable of stably
holding a powder fill,
and capable of disintegrating in the gastrointestinal track of an individual.
Capsules for use
herein may comprise any combination of animal gelatin, plant polysaccharides
(carrageenan,
etc.), or starch or derivatives thereof. In some instances, capsules may
further comprise
plasticizers, colors, preservatives, disintegrants, lubricants, and various
surface treatments
such as laser perforations. In various embodiments, a capsule may be
transparent so that the
contents are visible, or entirely opaque to obscure the contents. In various
embodiments, the
rate of delivery of an AAI from a two piece hard capsule having a powder fill
may be
controlled by any combination of ingredients in the powder fill and
ingredients or design
configurations of the capsule itself For example, a capsule intended for
immediate release of
an active drug may comprise a micronized powder fill in combination with a
laser perforated
capsule having disintegrants incorporated in the capsule material. On the
other hand, a
capsule intended for slow or controlled release may have a powder fill
configured with a
CDRA, like a cellulosic, to coagulate in the gut, slowing active
bioavailability, in
combination with a slower dissolving capsule shell, such as one comprising a
plasticizer. In
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various embodiments, an AAI or other bioactive substance may be embedded in
the capsule
material.
[0048] Two piece hard capsules for use herein can be characterized by a
size scale that
includes size 5, 4, 3, 2, 1, 0, 0E, 00, 000, 13, 12, 12e1, 11, 10, 7 and Su07,
(in increasing order
of physical dimensions and internal volume when assembled). Typically, only
the capsule
sizes from 5 (11.1 mm x 4.91 mm, 0.13 mL volume) up through about 000 (26.14
mm x 9.91
mm, 1.36 mL) would be practical for human oral consumption, and digestive
tract (enteral)
route of administration.
[0049] As used herein, the term "subject" or the phrase "a subject in
need thereof' refers
to any human or non-human animal requiring or desirous of a pharmacological
change. For
example, a subject in need thereof may be a human patient clinically diagnosed
with obesity,
an eating disorder, or health issues relating to poor BMI, fat along the
waistline, diet in
general, or lack of exercise. In various embodiments, the subject in need
thereof is a person
desirous of a reduced appetite such that they can lose weight and/or improve
health. Most
importantly, a subject in need thereof can be any human in good health, but
desirous of
maintaining good health. In other words, the subject in need thereof may be
desirous of a
prophylactic regimen, like taking daily vitamins. The subject in need thereof
may have the
outward appearance of a person of average weight for their age, height and
gender, but
desirous of maintaining that weight, and thus desirous of curbing appetite in
general.
[0050] As used herein, the term "treatment" of a subject (e.g., a human) is
any type of
intervention used in an attempt to alter the natural course of the subject.
Treatment includes,
but is not limited to, administration of an appetite suppressant composition
in accordance
with the present disclosure, and may be performed either prophylactically or
subsequent to
the initiation of a pathologic event or diagnosis of a physical issue, such as
obesity. Also
included are "prophylactic" treatments, which can be directed to reducing the
rate of
progression of obesity or condition being treated, delaying the onset of
weight or condition,
or reducing the severity of its onset. "Treatment" or "prophylaxis" does not
necessarily
indicate complete eradication, cure, or prevention of a disease or condition,
or associated
symptoms thereof. Treatment may also be entirely for cosmetic reasons, such as
where an
individual has not received any diagnosis of having a weight issue or a need
for weight loss,
but for whom obtaining or maintaining a slim figure is desirous for some
reason, such as to
succeed in a particular profession.
[0051] As used herein, the term "therapeutically effective amount" refers
to a minimum
dosage of a composition in accordance with the present disclosure that
provides a desired
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effect. Therefore, a therapeutically effective amount varies by subject,
dosage form,
concentration of one or more AAIs in the composition, and the ultimate results
desired. For
example, a therapeutically effective amount of a capsule disclosed herein to
treat an
overweight individual might be on the order of three (3) 150 mg capsules per
day. In other
examples, a therapeutically effective amount of a capsule disclosed herein to
treat a morbidly
obese individual might be on the order of six (6) 150 mg capsules per day.
[0052] As used herein, the term "prophylactically effective amount"
refers to a minimum
dosage of an appetite suppressant composition in accordance with the present
disclosure that
provides maintenance of a desired level of health. Therefore, a
prophylactically effective
amount varies by subject, (particularly age, gender, height, weight, and
current health habits
and any ongoing health issues), dosage form, concentration of one or more AAIs
in a
composition, and the results desired. For example, a prophylactically
effective amount of a
capsule composition disclosed herein to promote general health in a male of
fairly average
weight who exercises moderately may be one (1) 150 mg capsule per day, such as
before
dinner or when that individual fears overeating.
[0053] As used herein, the term "modulate" includes to "increase" or
"decrease" one or
more quantifiable parameters, optionally by a defined and/or statistically
significant amount.
By "increase" or "increasing," "enhance" or "enhancing," or "stimulate" or
"stimulating,"
refers generally to the ability of one or more appetite suppressant
compositions in accordance
with the present disclosure to produce or cause a greater physiological
response (i.e.,
downstream effects) in a cell or in a subject relative to the response caused
by either no
appetite suppressant composition or a control compound. Relevant physiological
or cellular
responses (in vivo or in vitro) upon administration of appetite suppressant
compositions will
be apparent to persons skilled in the art. An "increased" or "enhanced" amount
is typically a
"statistically significant" amount, and may include an increase that is 1.1,
1.2, 2, 3, 4, 5, 6, 7,
8, 9, 10, 15, 20, 30, 40, 50 or more times (e.g., 500, 1000 times), including
all integers and
decimal points in between and above 1 (e.g., 1.5, 1.6, 1.7. 1.8), the amount
produced by no
appetite suppressant composition (the absence of a bioactive agent) or a
control compound.
The term "reduce" or "inhibit" may relate generally to the ability of one or
more appetite
suppressant compositions to "decrease" a relevant physiological or cellular
response, such as
a symptom of a disease like obesity or a condition like excessive weight
described herein, as
measured according to routine techniques in the diagnostic art. Relevant
physiological or
cellular responses (in vivo or in vitro) will be apparent to persons skilled
in the art, and may
include reductions in the symptoms or pathology of a disease such as obesity
and related
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issues like inflammation or pain. A "decrease" in a response may be
"statistically significant"
as compared to the response produced by no appetite suppressant composition or
a control
composition, and may include a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%,
12%,
13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,
60%,
65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% decrease, including all integers in
between.
[0054] As used herein, the term "naturally occurring" refers to an AAI
obtained in its
active form from nature. In various embodiments, it is possible that an AAI is
not identifiable
or characterizable in a natural limn. For example, an AAI for use herein may
be a dried and
powdered plant leaf, containing hundreds of structurally complex organic
substances, but
which acts as an AAI even though there is no way to conclusively say what
substance or
substances in the complex mixture is providing the observed physiological
effect, i.e.,
appetite suppression. In other words, the true active or actives in a natural
material, like a
ground leaf, may never be known, but for simplicity, the natural material may
be referred to
as an AAI because of the effect it can elicit.
[0055] As used herein, the term "semisynthetic" refers to an AAI obtained
by one or
more reactions in synthetic organic chemistry, beginning with a naturally
occurring
substance. In other words, a naturally occurring substance may need to undergo
one or more
synthetic steps in a laboratory or chemical process plant to be ultimately
useful as an AAI for
a composition herein.
[0056] As used herein, the term "synthetic" refers to an AAI that is made
entirely by
organic synthesis, such as through a linear or convergent strategy, possibly
involving
asymmetric synthesis as needed to obtain a specific enantiomer of an AAI, such
as directing
formation of a chiral center using a chiral reagent.
[0057] As used herein, the term "approximately" in reference to amounts
refers to plus or
minus 5% of the value given, such as wt.%. The term "about," a in reference to
amounts
refers to plus or minus 10% of the value given, such as wt.%.
[0058] General embodiments
[0059] In various embodiments, an appetite suppressant composition in
accordance with
the present disclosure comprises: at least one AAI; and any one or combination
of a nutritive
substance, a CDRA, a cofactor, an excipient, and/or a filler. In various
embodiments, the AM
is selected from the group consisting of phentermine, diethylpropion,
phendimetrazine,
bupropion, naltrexone, prodrugs thereof, pharmaceutically acceptable salts
thereof, and
combinations thereof. In various embodiments, the nutritive substance
comprises a protein
source. In various embodiments, the CDRA comprises a cellulosic. In various
embodiments,
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the appetite suppressant composition is in the physical form of a loose powder
for filling
capsules, and wherein the dosage form to administer the composition comprises
an extended
release capsule. In various embodiments, the CDRA component is absent in the
loose powder
composition, and the dosage form to administer the composition comprises an
immediate
release capsule.
[0060] (I) In various embodiments, an appetite suppressant composition in
accordance
with the present disclosure comprises: at least one AAI; a nutritive
substance; a CDRA; a
cofactor; and optional excipients. In various embodiments, the AAI is selected
from the
group consisting of phentermine, diethylpropion, phendimetrazine, bupropion,
naltrexone,
prodrugs thereof, pharmaceutically acceptable salts thereof, and combinations
thereof. In
various embodiments, the nutritive substance comprises a protein source. In
various
embodiments, the CDRA comprises a cellulosic. In various embodiments, the
appetite
suppressant composition is in the physical form of a loose powder for filling
capsules, and
wherein the dosage form to administer the composition comprises an extended
release
capsule.
[0061] (II) In various embodiments, an appetite suppressant composition
in accordance
with the present disclosure comprises: at least one AAI; a CDRA; and optional
excipients. In
various embodiments, the AAI is selected from the group consisting of v In
various
embodiments, the CDRA comprises a cellulosic. In various embodiments, the
appetite
suppressant composition is in the physical form of a loose powder for filling
capsules, and
wherein the dosage form to administer the composition comprises an extended
release
capsule.
[0062] (III) In various embodiments, an appetite suppressant composition
in accordance
with the present disclosure comprises: at least one AAI; a nutritive
substance; a cofactor; and
optional excipients. In various embodiments, the AAI is selected from the
group consisting of
phentermine, diethylpropion, phendimetrazine, bupropion, naltrexone, and
combinations
thereof In various embodiments, the appetite suppressant composition is in the
physical
form of a loose powder for filling capsules, and wherein the dosage form to
administer the
composition comprises an immediate release capsule.
[0063] In these general embodiments of appetite suppressant compositions,
the at least
one AAI is present (at a combined weight if more than one) from about 0.1 wt.%
to about
10.0 wt.%, based on the total weight of the composition, and depending on the
actual AAI
chemical species used and the desired strength of the AAI(s) in the finished
dosage form. In
various embodiments, any AAI may be in the form of a pharmaceutically
acceptable salt,
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such as the hydrochloride salt, or tartrate salt, or other salt to provide a
more water soluble
form.
[0064] In general embodiments of appetite suppressant compositions
comprising a
protein source as the nutritive substance, the protein source may be selected
from the group
consisting of a dried Spirulina algal species biomass powder having > about 60
wt.% protein
(e.g., S. platensis, S. maxima), a dried Chlorella algal species biomass
powder having > about
60 wt.% protein (e.g., C. pyrenoidosa, C. vulgaris), (available from Nanjing
NutriHerb
BioTech Co., LTD, Nanjing, China), a hydrolyzed powdered animal collagen
(e.g., bovine or
fish), a gelatin powder (e.g., bovine or porcine collagen that has been
partially hydrolyzed),
egg albumin powder, calcium caseinate powder, powdered milk protein
concentrate (many of
the above-mentioned animal derived protein raw material powders are available
from Heathy
Solutions, LLC, Scottsdale AZ, USA), whey protein isolate powder (from Antler
Farms ,
Hornby South, Christchurch, New Zealand), or a dried legume, grain, vegetable,
nut or seed
protein isolate or hydrosylate powder (from brown rice, lentils, yellow pea,
or hemp seeds,
particularly yellow pea protein isolate), available, e.g., from AXIOM Foods,
Los Angeles,
CA, USA. See, J. Y. Nehete, "Natural proteins: Sources, isolation,
characterization and
applications," Pharmaeogn. Rev., 7(14) 107-116 (2013).
[0065] Table 1 sets forth these three general embodiments (I, II, III) in
accordance with
the present disclosure. The compositions are in the physical form of a loose
powder, which
can be loaded into capsules to provide dosage forms for oral administration.
General
embodiments I and II encompass the compositions for use in a controlled
(extended) release
dosage form, whereas general embodiment III encompasses the compositions for
use in an
immediate release dosage form. In any of the specific compositions under I,
II, and III, the
loose fill composition may be loaded into two-piece hard shell capsules. The
capsule shell
may be modified as necessary to be more appropriate for controlled release
versus immediate
release.
[0066] TABLE 1: General Appetite Suppressant Compositions
. __ .
Compositions
Ingredient (wt %) I II III
Anorectic Active Ingredient(s) (AM) 4 to 25 40 to 65 5 to 20
Controlled Drug Release Agent (CDRA) 40 to 50 35 to 60 -0-
Nutritive Substance (e.g., a protein source) 10 to 50 -0- 50
to 85
Cofactor 0.01 to 0.1 -0- 0.01 to 0.1
Excipients (color, flavor, etc.) 0 to 40 __ 0 to 40 0 to 40
L.
Total 100.00 wt.% 100.00 wt.% 100.00 wt.%
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Physical Appearance Loose powder Loose powder Loose
powder
Extended Extended Immediate
IJse
Release Release Release
[0067] In various embodiments, any combination of the at least one
nutritive substance
and the at least one CDRA may be used to bulk the composition "quantity
sufficient" to 100
% total. In other words, the AAI and the cofactor are likely to be the most
important in a
dosage regimen, whereas the CDRA, like a cellulosic substance, and the
nutritive substance,
like a protein powder, can vary as necessary to make up the remainder of a
capsule fill.
[0068] In various embodiments, the AAI is selected from the group
consisting of
phentermine, dietbylpropion, phendimetrazine, bupropion, naltrexone, and
combinations
thereof. In various embodiments, the AM consists of phentermine used on its
own. In
various embodiments, the AAI is phentermine-HCl. In various embodiments,
consists of
phendimetrazine used on its own. In various embodiments, the AAI is
phendimetrazine
tartrate. In various embodiments, the AAI is diethylpropion used on its own.
In various
embodiments, the AAI is diethylpropion HCl with 1% tartaric acid. In various
embodiments,
the AAI is a combination of naltrexone and bupropion. In various embodiments,
the AAI is a
mixture of naltrexone-HC1 and bupropion-HC1.
[0069] In various embodiments, the appetite suppressant composition
contain no inert
filler, although recognizing a cellulosic CDRA is non-nutritive, and thus acts
as a filler as
discussed above. In other words, in certain variations, the only non-nutritive
substance in an
appetite suppressant composition in accordance with the present disclosure is
the CDRA,
such as if it is cellulosic and hence not digestible.
[0070] In various embodiments, an appetite suppressant composition in
accordance with
the present disclosure comprises any combination of optional excipients. In
various
embodiments, an appetite suppressant composition contains no excipients. In
some instances,
there is no taste to mask in a swallowed capsule, and perhaps no need for
colorants,
sweeteners or preservatives. Depending on the AAI, and whether a filled
capsule is designed
for extended release or immediate release, it may be necessary to include a
flavorant.
[0071] In various embodiments, the optional one or more excipients
include any one or
combination of flavorant, sweetener, buffer (or acidic agent and/or alkali
agent), colorant,
disintegrant, intestinal permeation enhancer, stabilizer, preservative, or
other
pharmaceutically acceptable substance. Any of these materials not specifically
mentioned
herein may be found in "Handbook of Pharmaceutical Excipients, 6th Edition, R.
C Rowe, et
al., editors, Pharmaceutical Press, London, 2009, mentioned above in the
context of "fillers."
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For liquid excipients, or excipients that might be better dispersed if
provided in solution, the
substance may be sprayed into a ribbon blender with a spray bar as a powdered
composition
is blending. In this way, a dry blended powder is still obtained, even though
small amounts
of liquid ingredients are absorbed in homogeneously.
[0072] Suitable flavomnts can include, for example, flavors, such as,
natural flavors,
artificial flavors, and combinations thereof Non-limiting examples of flavor
oils include
spearmint oil, cinnamon oil, oil of wintergreen (methyl salicylate),
peppermint oil, clove oil,
bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, oil of nutmeg,
allspice, oil of sage,
mace, oil of bitter almonds, and cassia oil. Suitable flavoring agents also
include, for
example, artificial, natural and synthetic fruit flavors such as vanilla,
citrus oils (e.g., lemon,
orange, lime, and grapefruit), and fruit essences (e.g., apple, pear, peach,
grape, strawberry,
raspberry, cherry, plum, pineapple, and apricot), and the like, and
combinations thereof.
[0073] Other flavorants and fragrant aromatics that may be included
individually or in
combination include, but are not limited to, anethole, menthol, menthone,
menthyl acetate,
eucalyptol, bomeol, borneol acetate, camphor, 1,8-cineole, cinnamaldehyde,
benzaldehyde,
citral, thujone, eugenol, limonene, geraniol, citronellol, citronellal,
pinene, linalool, thymol,
carvone, caryophyllene, linalyl acetate, methyl salicylate, and mixtures
thereof. Also,
substances that provide scent and flavor include, but are not limited to,
3,3,5-
trimethylcyclohexanol, methoxycyclohexanol, benzyl alcohol, anise alcohol,
cinnamyl
alcohol, 13-phenyl ethyl alcohol (2-phenylethanol), cis-3-hexenol, musk xylol,
isoeugenol,
methyl eugenol, a-amylcinnamic aldehyde, anisaldehyde, n-butyl aldehyde, cumin
aldehyde,
cyclamen aldehyde, decanal, isobutyl aldehyde, hexyl aldehyde, heptyl
aldehyde, n-nonyl
aldehyde, nonadienol, hydroxycitronellal, benzaldehyde, methyl nonyl
acetaldehyde,
dodecanol, a-hexylcinnamic aldehyde, undecenal, heliotropin, vanillin, ethyl
vanillin, methyl
amyl ketone, methyl p-naphthyl ketone, methyl nonyl ketone, musk ketone,
diacetyl, acetyl
propionyl, acetyl butyryl, acetophenone, p-methyl acetophenone, ionone, methyl
ionone,
amyl butyrolactone, diphenyl oxide, methyl phenyl gly-cidate, y-nonyl lactone,
coumarin,
cineole, ethyl methyl phenyl glycidate, methyl formate, isopropyl formate,
linalyl formate,
ethyl acetate, octyl acetate, methyl acetate, benzyl acetate, butyl
propionate, isoamyl acetate,
isopropyl isobutyrate, geranyl isovalerate, allyl capronate, butyl heptylate,
octyl caprylate
octyl, methyl heptynecarboxylate, methine octynecarboxylate, isoacyl
caprylate, methyl
laurate, ethyl myristate, methyl myristate, ethyl benzoate, benzyl benzoate,
methylcarbinylphenyl acetate, isobutyl phenylacetate, methyl cinnamate,
cinnamyl
cinnamate, ethyl anisate, methyl anthranilate, ethyl pyruvate, ethyl a-butyl
butylate, benzyl
19
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Docket No. 58872.00303
propionate, butyl acetate, butyl butyrate, p-tert-butylcyclohexyl acetate,
cedryl acetate,
citronellyl acetate, citronellyl formate, p-cresyl acetate, ethyl butyrate,
ethyl caproate, ethyl
cinnamate, ethyl phenylacetate, ethylene brassylate, geranyl acetate, geranyl
formate, isoamyl
salicylate, isoamyl isovalerate, isobornyl acetate, linalyl acetate, methyl
anthranilate, methyl
dihydrojasmonate, P-phenylethyl acetate, trichloromethylphenyl carbinyl
acetate, terpinyl
acetate, vetiveryl acetate, and mixtures thereof.
[0074] Suitable sweeteners include nutritive carbohydrates such as
sucrose, glucose,
fructose, glucose, trehalose, galactose, mannitol, sorbitol, xylitol and
artificial sweeteners
such as saccharin, aspartame, acesulfame K, cyclamates, neotame, sucralose,
stevia, and
neohesperidin dihydrochalcone (NHDC).
[0075] Suitable buffers may comprise one or more acidifying agents or
alkaline agents as
necessary to neutralize various co-ingredients, form salts of various co-
ingredients, and/or
achieve a particular pH target for the composition, such as to adjust the
local environment in
the GI tract as a dosage foini dissolves. For liquid appetite suppressant
compositions, it may
.. be desirable to adjust the pH of the liquid composition. Combinations of
various acidifying
agents and alkaline agents may be used to create buffering systems that
stabilize the desired
final pH of the composition. Buffers may be mixed buffers, meaning that the
alkaline agent
is not necessarily the conjugate base of the acidifying agent.
[0076] Exemplary acidifying agents for use in the present compositions
include, but are
not limited to, organic acids of any molecular weight and mineral acids
(inorganic acids), and
mixtures thereof Organic acids may include mono-carboxylic acids, di-
carboxylic acids, or
tri-carboxylic acids, and may be saturated or may have any degree of
unsaturation. For
example, organic acids for use in various embodiments of the composition in
accordance to
the present disclosure may include, but are not limited to, formic acid,
carbonic acid, acetic
acid, lactic acid, oxalic acid, propionic acid, valeric acid, enanthic acid,
pelargonic acid,
butyric acid, lauric acid, docosahexaenoic acid, eicosapentaenoic acid,
pyruvic acid,
acetoacetic acid, benzoic acid, salicylic acid, aldaric acid, fiimaric acid,
glutaconic acid,
traumatic acid, muconic acid, malonic acid, malic acid, succinic acid,
glutaric acid, adipic
acid, pirnelic acid, suberic acid, azelaic acid, abietic acid, pimaric acid,
sebacic acid, phthalic
acid, isophthalic acid, terephthalic acid, maleic acid, citric acid, and
combinations thereof.
[0077] Exemplary alkaline materials include any organic amines, NH3,
alkali metal or
alkaline earth hydroxide, any conjugate bases of any organic acids (e.g. R-
000), and any of
the salts of carbonic acid, phosphoric acid, nitric acid and sulfuric acid,
and any mixtures
thereof. For example, alkaline materials for use in various embodiments of the
composition in
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accordance to the present disclosure may include, but are not limited to,
NaOH, KOH, NH3,
sodium acetate, sodium succinate, disodium succinate, monosodium citrate,
disodium citrate,
trisodium citrate, Na1-l2PO4, Na2HPO4, Na3PO4, KH2PO4, K2HPO4, K3PO4, NaHSO4,
Na2SO4,
KHSO4, K2SO4, NaHCO3, Na2CO3, KHCO3, K2CO3, NaH3P207, Na2H2P207, Na3HP207,
Na4P207, KH3P207, K2H2P207, K3HP207, K4P207, and mixtures thereof. Any of
these
chemical species may exist as various hydrates when purchased as raw materials
for use in the
present compositions.
[0078] Exemplary colorants include the pharmaceutically acceptable colors
used for
capsules and tablet dosage forms, such as the US FDA certified colors, dyes
and lakes for use
in pharmaceutical capsules, tablets and syrups. These acceptable colorants
include the
inorganic pigments such as titanium dioxide, yellow iron oxide, red iron oxide
and black iron
oxide, the organic pigments such as D&C Red 36, Red 30 and Red 34, the solvent
soluble
colors D&C Yellow 11, Yellow 7, Red 27, Red 21, Red 17, Green 6, and Violet 2,
and the
water soluble colors D&C Green 8, Yellow 10, Yellow 8, Orange 4, Red 22, Red
28, Red 33,
Green 5, quinoline yellow, FD&C Yellow 5, Yellow 6, Red 4, Red 40, Red 3,
Green 3, Blue
1, Blue 2, and ponceau 4R, carmoisine, amaranth, patent blue V and black PN,
and a number
of "organic lakes."
[0079] Suitable disintegrants include, but are not limited to, sodium
starch glycolate,
croscarmellose sodium, microcrystalline cellulose, and crospovidone. Some
substances known
to be disintegrants can act as CDRAs as well, since the swelling of an
ingredient can not only
break apart other structures but can occlude drug actives. For a review of
disintegrants that
find use in the present compositions, see P. M. Desai, "Review of
Disintegrants and the
Disintegration Phenomena," J Pharm. Sci., 105, 2545-2555 (2016).
[0080] Suitable intestinal permeation enhancers include, but are not
limited to surfactants
that assist bio-absorption, including, for example, fatty acids and/or esters
or salts thereof, bile
acids and/or salts thereof. Bile acids/salts and fatty acids and their uses
are further described in
U.S. Pat. No. 6,287,860. In some embodiments, the present disclosure provides
combinations
of absorption enhancers, for example, fatty acids/salts in combination with
bile acids/salts. An
exemplary combination is the sodium salt of lauric acid, capric acid and
ursodeoxycholic acid
(UDCA) for promoting improved intestinal absorption of peptides and other
materials. These
excipients may be used in the present compositions to assist absorption of the
AAI and/or the
protein source, such as hydrolyzed animal or plant proteins. Further
penetration enhancers
include, but are not limited to, polyoxyethylene-9-latuyl ether,
polyoxyethylene-20-cetyl ether.
21
Date Recue/Date Received 2021-10-05

For a review of absorption enhancers that find use herein, see B. J. Aungst,
"Intestinal
Permeation Enhancers," I Pharm. Sc!., 89(4), 429 (2000).
[0081] Stabilizers and preservatives are generally more important for
liquid compositions
rather than dry powder compositions. Such substances for oral compositions
include the
parabens, sorbitol, sodium benzoate, benzoic acid, sorbic acid, potassium
sorbate, propionic
acid, and combinations thereof Antioxidants include, but are not limited to,
vitamin C, vitamin
E, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and
propylgallate. In
some instances, the antioxidant, such as a vitamin, can double as a nutritive
substance in the
appetite suppressant composition. For a review see, I. Himoudy, "Preservatives
and their role
in pharma and clinical research," International Journal of Pharma Sciences and
Scientific
Research, 2:4, 134-151 (2016).
[0082] The appetite suppressant compositions of the present disclosure
may also include
surfactants. The use of surfactants in drug products, formulations and in
emulsions is well
known in the art. Surfactants and their uses are further described in U.S.
Pat. No. 6,287,860.
[0083] Exemplary compositions, dosage forms, and methods of administration
[0084] Table 2 sets forth exemplary appetite suppressant compositions in
accordance with
the present disclosure. Each of these compositions are obtained by dry-
blending each of the
dry ingredients in a V-blender (e.g., MAXIBLEND lab blender) or other
suitable mixer
configured for mixing dry ingredients. Liquid colorants may be sprayed into
the blender with
a spray nozzle. Each of the exemplary composition in Table 2 appear as loose
powders and
each were filled into two-piece hard shell capsules at the fill weights
indicated.
[0085] TABLE 2: Exemplary Appetite Suppressant Compositions and Dosages:
1 2 3 4 5 6 7 8
AAI 4.80'
7.35' 14.42' 13.50' 15.372 9.103 25.413 42.954 63.574
CDRA 44.625 45.505 44.625 40.345 -0- -
0- 47.425 57.016 36.406
Nutritive' 50.50 47.07 40.88 46.10 84.55 54.50 10.16 -0- -0-
Cofactor' 0.08 0.08 0.08 0.06 0.08 0.07 0.07 -0-
-0-
Excipients9 -0- -0- -0- -0- -0- 36.33 16.94 0.04
0.03
Total 100%
100% 100% 100% 100% 100% 100% 100% 100%
Capsule Fill 260mg 255mg 260mg 347mg 260mg 275mg 295mg 256mg 346mg
22
Date Recue/Date Received 2021-10-05

Docket No. 58872.00303
[0086] TABLE 2 notes: (1) preferably phentermine-HC1; (2) preferably
phendimetrazine
tartrate; (3) preferably diethylpropion-HCl with 1% tartaric acid; (4)
preferably a 1:10 ratio of
naltrexone-HC1 to bupropion-HC1; (5) preferably hydroxypropyl methylcellulose;
(6)
preferably a 10:1 to about a 3:1 ratio of hydroxypropyl methylcellulose and
microcrystalline
cellulose; (7) preferably hydrolyzed collagen; (8) preferably chromium
picolinate; and (9)
preferably combinations of peppermint flavorant and/or colorants. The empty
gelatin
capsules used in these examples were size 1 (70 mg empty) and size 0 (90 mg
empty).
[0087] Besides cellulosic CDRAs, which arguably are fillers in a sense,
being non-
digestive, the appetite suppressant compositions of Table 2 are absent inert
fillers typically
used in capsule and other oral dosage forms to provide bulk and weight. Thus,
in various
embodiments, appetite suppressant compositions according to the present
disclosure comprise
no inert filler.
[0088] In various embodiments, the AAI is selected from the group
consisting of
diethylpropion, amphetamine, benfluorex, bupropion, butanolide, caffeine,
cathine, cetilistat,
clobenzorex, D-fenfluramine, racemic-fenfluramine, ephedrine, etilarnfetamine,
exenatide,
FG-7142 (diazepine inverse agonist), higenamine, liraglutide, lorcaserin,
mazindol,
mefenorex, metformin, methamphetamine, naltrexone, nicotine, orlistat,
phenmetrazine,
phendimetrazine, phentermine, phenylpropanolamine, pramlinatide,
pseudoephedrine,
pyroglutamyl-histidyl-glycine, rimonabant, semaglutide, sibutramine,
topiramate, yohimbine,
pro-drugs thereof, pharmaceutically acceptable salts thereof, and combinations
thereof.
[0089] In various embodiments, the CDRA, when present for a controlled
release
composition, is selected from the group consisting of agar, agarose, albumin,
alginate, casein,
chitin, chondroitin, dextrin, fibroin, fucoidan, galactan, gellan, guar,
scleroglucan, pullulan,
xyloglucan, pectin, xanthan, psyllium, silica gel, fumed silica, magnesium
aluminum silicate,
clay, bentonite, hectorite, mesoporous silica, cellulose, cellulose acetate,
hyaluronan, elastin-
like polypeptides, P-cyclodextrin, collagen, gelatin, chitosan, carrageenan,
polylactic acid,
polyglycolic acid, poly(lactic-glycolic acid) (PLGA), poly(2-hydroxyethyl
methacrylate),
poly(2-hydroxypropyl methacrylate), poly(acrylic acid), carboxymethyl
cellulose,
carboxyethyl cellulose, hydroxyethyl cellulose, hydrophobically-modified
hydroxyethyl
cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl
cellulose, ethyl
cellulose, microcrystalline cellulose, nitrocellulose, polyvinyl alcohol,
polyvinylpyrrolidone,
polyvinylmethacrylate, carboxyvinyl polymers, polyvinylacetate, polyvinyl co-
polymers,
starch, modified starches, and combinations thereof.
23
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Docket No. 58872.00303
[0090] In various embodiments, the nutritive, when present, is selected
from the group
consisting of a dried Spirulina algal species biomass powder, a dried
Chlorella algal species
biomass powder, a hydrolyzed powdered bovine or fish collagen, a bovine or
porcine gelatin
powder, egg albumin powder, calcium caseinate powder, powdered milk protein
concentrate,
whey protein isolate powder, yellow pea protein isolate, and combinations
thereof. "
[0091] In various embodiments, the cofactor, when present, is selected
from the group
consisting of calcium acetate, calcium ascorbate, calcium citrate, calcium
gluconate, calcium
nicotinate, calcium picolinate, chromium acetate, chromium ascorbate, chromium
citrate,
chromium gluconate, chromium nicotinate, chromium picolinate, copper acetate,
copper
ascorbate, copper citrate, copper gluconate, copper nicotinate, copper
picolinate, magnesium
acetate, magnesium ascorbate, magnesium citrate, magnesium gluconate,
magnesium
nicotinate, magnesium picolinate, manganese acetate, manganese ascorbate,
manganese
citrate, manganese gluconate, manganese nicotinate, manganese picolinate,
potassium
acetate, potassium ascorbate, potassium citrate, potassium gluconate,
potassium nicotinate,
potassium picolinate, selenium acetate, selenium ascorbate, selenium citrate,
selenium
gluconate, selenium nicotinate, selenium picolinate, zinc acetate, zinc
ascorbate, zinc citrate,
zinc gluconate, zinc nicotinate, zinc picolinate, and mixtures thereof:
[0092] In various embodiments, the excipients, when present, are selected
from the group
consisting of flavorants, colorants, and mixtures thereof.
[0093] With reference to TABLE 2, compositions 1-7 each benefit from the
unusual
combination of hydrolyzed bovine collagen and chromium picolinate in an
extended release
oral dosage form. This combination unexpectedly provides synergistic
maintenance of a
healthy gut barrier, along with increasing metabolism, stabilizing blood sugar
levels,
promoting weight loss and body fat, while increasing lean body mass. The
combination
further appears to improve skin elasticity, improve hair and nail appearance,
improve muscle
mass, improve heart health, relieve joint pain, and prevent bone loss. The
hydrolyzed bovine
collagen and chromium picolinate in an extended release oral dosage form
appears to reduce
hunger and cravings, and lower appetite, over extended periods of time, and
may enhance
insulin.
[0094] The appetite suppressant compositions of the present disclosure may
be
administered in a number of ways depending upon whether local or systemic
treatment is
desired. Administration may be topical (including ophthalmic and to mucous
membranes
including vaginal and rectal delivery), pulmonary, e.g., by inhalation or
insufflation of
powders or aerosols, including by nebulizer; intratracheal, intranasal,
epidermal and
24
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Docket No. 58872.00303
transdermal), oral or parenteral. Parenteral administration includes
intravenous, intraarterial,
subcutaneous, intraperitoneal or intramuscular injection or infusion; or
intracranial, e.g.,
intrathecal or intraventricular, administration. Appetite suppressant
compositions for topical
administration may include transdermal patches, ointments, lotions, creams,
gels, drops,
suppositories, sprays, liquids and powders. Conventional pharmaceutically
acceptable
carriers, aqueous, powder or oily bases, thickeners and the like, may be
necessary or
desirable. In various embodiments, appetite suppressant compositions comprise
loose
powders that are filled into dissolvable capsules for oral administration and
gastrointestinal
absorption.
[0095] The appetite suppressant compositions of the present disclosure,
which may
conveniently be presented in unit dosage form such as a capsule, may be
prepared according
to conventional techniques well known in the pharmaceutical industry. Such
techniques
include the step of bringing into association the at least one AAI with the
pharmaceutically
acceptable carrier(s) or excipient(s), which in various embodiments comprises
a nutritive
base. In general, the appetite suppressant compositions are prepared by
uniformly and
intimately bringing into association the AM(s) with finely divided solid
carriers or both, and
then, if necessary, shaping the product by addition of various excipients.
[0096] The appetite suppressant compositions of the present disclosure
may be
formulated into any of many possible dosage forms such as, but not limited to,
tablets,
capsules, gel capsules, liquids, liquid syrups, soft gels, suppositories, and
enemas. The
compositions of the present disclosure may also be formulated as suspensions
in aqueous,
non-aqueous or mixed media. Aqueous suspensions may further contain substances
which
increase the viscosity of the suspension or help to stabilize the suspension.
[0097] One of skill in the art will recognize that compositions are
routinely designed
according to their intended use, i.e., route of administration.
[0098] Appetite suppressant compositions for oral administration include
powders or
granules, microparticulates, nanoparticulates, capsules, gel capsules,
sachets, tablets or
minitablets. Oral formulations are those in which at least one AM of the
present disclosure is
administered in conjunction with one or more CDRAs, surfactants, chelators,
bio-absorption
promotors such as intestinal permeation enhancers, or other active or
nonactive excipients.
[0099] Dosage Regimens
[00100] In various embodiments of, methods of appetite suppression are
described. In
general, a method of suppressing appetite in an individual in need thereof
comprises orally
administering to the individual a therapeutically effective amount of an
appetite suppressant
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Docket No. 58872.00303
composition comprising at least one AAI. In various embodiments, the
individual in need
thereof has been diagnosed as overweight and obese, as per ICD-10 code E66 and
subgroups.
This diagnosis is discussed in S. B. Gribsholt, et al., "Validity of ICD-10
diagnoses of
overweight and obesity in Danish hospitals," Clin. Epidemiol.,11, 845-854
(2019).
[00101] In various embodiments, a method of suppressing appetite in an
individual in need
thereof comprising orally administering to the individual a therapeutically
effective amount
of an appetite suppressant composition comprising: at least one AAI; at least
one of a
nutritive substance, a CDRA, and a cofactor; and optionally an excipient. In
various
embodiments, the AAI is selected from the group consisting of diethylpropion,
amphetamine,
ben fluorex, bupropion, butanolide, caffeine, cathine, cetilistat,
clobenzorex, D-fenfluramine,
racemic-fenfluramine, ephedrine, etilamfetamine, exenatide, FG-7142 (diazepine
inverse
agonist), higenamine, liraglutide, lorcaserin, mazindol, mefenorex, metformin,
methamphetamine, naltrexone, nicotine, orlistat, phemnetrazine,
phendimetrazine,
phentermine, phenylpropanolamine, pramlinatide, pseudoephedrine, pyroglutamyl-
histidyl-
glycine, rimonabant, semaglutide, sibutramine, topirarnate, yohimbine, pro-
drugs thereof,
pharmaceutically acceptable salts thereof, and combinations thereof. In
various embodiments,
the AAI is selected from the group consisting of phentermine, diethylpropion,
phendimetrazine, bupropion, naltrexone, prodrugs thereof, pharmaceutically
acceptable salts
thereof, and combinations thereof.
[00102] Appetite suppressant compositions of the present disclosure may be
delivered
orally, in granular form including sprayed dried particles, or complexed to
form micro or
nanoparticles, which may be administered as a loose powder that can be mixed
into a
beverage, or packed into capsules for swallowing. In various embodiments, the
appetite
suppressant composition comprise dry blended loose powders, with the dosage
form
comprising a capsule comprising the dry blended loose powder contained
therein.
[00103] Capsule dosages are in large part based on the AAI(s) present in the
powder
composition within the capsule. Generally, the following dosage regimens apply
for those
individuals in need thereof that received ICD-10 diagnosis:
[00104] Phentermine ¨ dosing up to 75 mg daily, with a time period of up to
twice daily;
[00105] Diethylpropion ¨ dosing up to 150 mg daily, with a time period of up
to four times
daily;
[00106] Phendimetrazine ¨ dosing up to 210 mg daily, with a time period of up
to three
times daily; and
26
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Docket No. 58872.00303
[00107] Bupropion/Naltrexone ¨ dosing up to 400 mg/40 mg daily, with a
time period of
up to twice daily.
[00108] For the preferred AAIs in the compositions and capsules outlined in
Table 2, the
following amounts and dosages are relevant:
[00109] Composition 1: each capsule contains 12.5 mg phentermine-HC1. Thus, a
therapeutically effective amount of composition 1 comprises from 1 up to about
6 capsules
per day;
[00110] Composition 2: each capsule contains 18.8 mg phentermine-HC1. Thus, a
therapeutically effective amount of composition 2 comprises from 1 up to about
4 capsules
per day;
[00111] Composition 3: each capsule contains 37.5 mg phentermine-HC1. Thus, a
therapeutically effective amount of composition 3 comprises from 1 to about 2
capsules per
day;
[00112] Composition 4: each capsule contains 46.9 mg phentermine-HC1. Thus, a
therapeutically effective amount of composition 4 comprises from 1 to about 2
capsules per
day;
[00113] Composition 5: each capsule contains 40 mg phendimetrazine tartrate.
Thus, a
therapeutically effective amount of composition 5 comprises from 1 up to about
5 capsules
per day;
[00114] Composition 6: each capsule contains 25 mg diethylpropion-IIC1. Thus,
a
therapeutically effective amount of composition 6 comprises from 1 up to about
6 capsules
per day;
[00115] Composition 7: each capsule contains 75 mg diethylpropion-HCl. Thus, a
therapeutically effective amount of composition 7 comprises from 1 up to about
2 capsules
per day;
[00116] Composition 8: each capsule contains 10 mg naltrexone-HCl and 100 mg
bupropion-HC1. Thus, a therapeutically effective amount of composition 8
comprises from 1
up to about 4 capsules per day; and
[00117] Composition 9: each capsule contains 20 mg naltrexone-HCl and 200 mg
bupropion-HC1. Thus, a therapeutically effective amount of composition 9
comprises from 1
up to about 2 capsules per day.
[00118] Appetite suppressant compositions and methods thereof are provided. hi
the
detailed description herein, references to "various embodiments", "one
embodiment", "an
embodiment", "an example embodiment", etc., indicate that the embodiment
described may
27
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include a particular feature, structure, or characteristic, but every
embodiment may not
necessarily include the particular feature, structure, or characteristic.
Moreover, such phrases
are not necessarily referring to the same embodiment. Further, when a
particular feature,
structure, or characteristic is described in connection with an embodiment, it
is submitted that
it is within the knowledge of one skilled in the art to affect such feature,
structure, or
characteristic in connection with other embodiments whether or not explicitly
described. After
reading the description, it will be apparent to one skilled in the relevant
art(s) how to implement
the disclosure in alternative embodiments.
[00119] Benefits, other advantages, and solutions to problems have been
described
herein with regard to specific embodiments. However, the benefits, advantages,
solutions to
problems, and any elements that may cause any benefit, advantage, or solution
to occur or
become more pronounced are not to be construed as critical, required, or
essential features or
elements of the disclosure. The scope of the disclosure is accordingly to be
limited by nothing
other than the appended claims, in which reference to an element in the
singular is not intended
to mean "one and only one" unless explicitly so stated, but rather "one or
more." Moreover,
where a phrase similar to 'at least one of A, B, and C' or 'at least one of A,
B, or C' is used in
the claims or specification, it is intended that the phrase be interpreted to
mean that A alone
may be present in an embodiment, B alone may be present in an embodiment, C
alone may be
present in an embodiment, or that any combination of the elements A, B and C
may be present
in a single embodiment; for example, A and B, A and C, B and C, or A and B and
C.
[00120] All structural, chemical, and functional equivalents to the elements
of the above-
described various embodiments that are known to those of ordinary skill in the
art. Moreover,
it is not necessary for a composition or method to address each and every
problem sought to be
solved by the present disclosure, for it to be encompassed by the present
claims. Furthermore,
no element, component, or method step in the present disclosure is intended to
be dedicated to
the public regardless of whether the element, component, or method step is
explicitly recited
in the claims. As used herein, the terms "comprises," "comprising," or any
other variation
thereof, are intended to cover a non-exclusive inclusion, such that a
chemical, chemical
composition, process, method, article, or apparatus that comprises a list of
elements does not
include only those elements but may include other elements not expressly
listed or inherent to
such chemical, chemical composition, process, method, article, or apparatus.
***
28
Date Recue/Date Received 2022-04-12

[001211 In some aspects, embodiments of the present invention as
described herein include
the following items:
Item 1. An appetite suppressant composition consisting essentially of:
from 4.0 wt.% to 16.0 wt.% phentermine hydrochloride;
from 40.0 wt.% to 46.0 wt.% hydroxypropyl methyl cellulose;
from 40.0 wt.% to 51.0 wt.% bovine collagen; and
from 0.05 wt.% to 0.10 wt.% chromium picolinate.
Item 2. A pharmaceutical dosage form for oral administration comprising: a
capsule; and the appetite suppressant composition of item 1 enclosed therein.
Item 3. Use of the appetite suppressant composition as defined in item 1 for
suppressing appetite in an individual in need thereof.
Item 4. Use of the appetite suppressant composition as defined in item 1 in
the
manufacture of a medicament for suppressing appetite in an individual in need
thereof.
Item 5. The use of item 3 or 4, wherein the use comprises up to 75 mg per day
of
the phentermine hydrochloride.
Item 6. The use of any one of items 3 to 5, wherein the individual in need
thereof
is diagnosed overweight and obese.
Item 7. An appetite suppressant dosage form consisting essentially of:
250 mg to 350 mg of the appetite suppressant composition of item 1 as a loose
powder; and
a dissolvable capsule enclosing said appetite suppressant composition.
Item 8. Use of the appetite suppressant dosage form of item 7 for suppressing
appetite in an individual in need thereof.
Item 9. Use of the appetite suppressant dosage form of item 7 in the
manufacture
of a medicament for suppressing appetite in an individual in need thereof.
Item 10. Use of the pharmaceutical dosage Ruin of item 2 for suppressing
appetite
in an individual in need thereof.
Item 11. Use of the pharmaceutical dosage form of item 2 in the manufacture of
a
medicament for suppressing appetite in an individual in need thereof.
29
Date regue/date received 2022-10-11