WO2017062956A1 - Capsule with internal diaphragm and solid ingredients - Google Patents

Capsule with internal diaphragm and solid ingredients Download PDF

Info

Publication number
WO2017062956A1
WO2017062956A1 PCT/US2016/056293 US2016056293W WO2017062956A1 WO 2017062956 A1 WO2017062956 A1 WO 2017062956A1 US 2016056293 W US2016056293 W US 2016056293W WO 2017062956 A1 WO2017062956 A1 WO 2017062956A1
Authority
WO
WIPO (PCT)
Prior art keywords
capsule
compartment
solid ingredients
lactobacillus
ingredients comprises
Prior art date
Application number
PCT/US2016/056293
Other languages
French (fr)
Inventor
Tobias Johan LOUW
Original Assignee
Binutra Incorporated
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Binutra Incorporated filed Critical Binutra Incorporated
Priority to CN201680071694.5A priority Critical patent/CN108366970A/en
Priority to EP16854537.4A priority patent/EP3359140A4/en
Priority to US15/767,036 priority patent/US11478429B2/en
Publication of WO2017062956A1 publication Critical patent/WO2017062956A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/203—Retinoic acids ; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4458—Non condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
    • A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/18—Iodine; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/42—Phosphorus; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/485—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K2035/11—Medicinal preparations comprising living procariotic cells
    • A61K2035/115—Probiotics

Abstract

A two-compartment capsule includes a body, a diaphragm between, which seals off the body and provides a first compartment to hold a first dry ingredient, and a cap applied to the body whereby a space between the inner portion of the cap and the diaphragm defines a second compartment for holding a second dry ingredient. This disclosure also provides particular formulations for use in such a capsule. Examples include a probiotic, a digestive enzyme, an expectorant, a bronchodilator, a stool softener, a platelet aggregation inhibitor, a form or derivative of vitamin E, a statin, and aspirin.

Description

CAPSULE WITH INTERNAL DIAPHRAGM AND SOLID INGREDIENTS
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to and benefit of U.S. Provisional Application Serial No. 62/239,435, filed October 9, 2015, entitled "Capsule with Volume- Adjustable Internal Diaphragm," U.S. Provisional Application Serial No. 62/239,454, filed October 9, 2015, entitled "Capsule with Internal Diaphragm for Improved Bioavailability," and U.S. Provisional Application Serial No. 62/239,442, filed October 9, 2015, entitled "Capsule with Internal Diaphragm and Solid Ingredients," each of which is hereby incorporated herein by reference in its entirety.
SUMMARY
[0002] Embodiments described herein are directed to a multi-compartment capsule comprising a body; a diaphragm, having two sidewalls and a bottom, extending into the body and defining a first compartment between an outer surface of the diaphragm and an inner surface of the body; and a cap mounted to an outer surface of the body and opposed to the diaphragm, and defining a second compartment between an inner surface of the diaphragm and the cap; wherein the two sidewalls of the diaphragm extend along the inner surface of the body and are aligned with an open end of the body. In some embodiments, the capsule is a size 00 capsule.
[0003] In some embodiments, the first compartment is hermetically sealed. In some embodiments, the one or more solid ingredients comprise a powder, a granule, a semisolid, a microbead, a beadlet, or a combination thereof.
[0004] In some embodiments, the bottom of the diaphragm may be flattened. In some embodiments, the bottom of the diaphragm may be curved. In some embodiments, the bottom of the diaphragm may be substantially or partially flattened.
[0005] In some embodiments, the first compartment and the second compartment each have sufficient volume to administer a therapeutically effective dose of an ingredient.
[0006] In some embodiments, the one or more solid ingredients comprises a probiotic. The probiotic may be selected from the group consisting of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus bulgaricus, Lactobacillus delbrueckii, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus salivarius, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus brevis, Lactobacillus breve, Streptococcus thermophilus, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium coagulans, Bifidobacterium breve, Bifidobacterium animalis, Bifidobacterium subtilis, Saccharomyces boulardi, and combinations thereof. In some embodiments, the one or more solid ingredients comprises from about 1 million colony forming units (CFUs) to about 100 billion CFUs of a probiotic.
[0007] In some embodiments, the one or more solid ingredients comprises a digestive enzyme. The digestive enzyme may be selected from the group consisting of amylase, alpha-amylase, protease, alpha-galactosidase, beta-gulcanase, galactomannase, lactase, lipase, cellulase, hemicellulase, phytase, sucrase, invertase, pectinase, maltase, malt diastase, glucoamylase, xylanase, pullulanase, peptidase and dipeptidyl peptidase IV, serratia peptidase, lysozyme, bromelian, papain, and combinations thereof. In some embodiments, the one or more solid ingredients comprises from about 50 mg to about 1000 mg of a digestive enzyme. In some embodiments, the first compartment comprises from about one million CFUs to about 10 billion CFUs of a probiotic, and the second compartment comprises from about 50 mg to about 1000 mg of a digestive enzyme. In some embodiments, the first compartment comprises from about 10 mg to about 1000 mg of a digestive enzyme, and the second compartment comprises from about 1 million CFUs to about 100 billion CFUs of a probiotic.
[0008] In some embodiments, the one or more solid ingredients comprises a pharmaceutical agent. In some embodiments, the pharmaceutical agent is selected from the group consisting of aspirin, a statin, ipriflavone, cohosh, castus, coenzyme Q10 (CoQI O), guaifenesin, althea root, antimony pentasulfide, creosote, guaiacolsulfonate, ipecacuanha (syrup of ipecac), levoverbenone, potassium iodide, senega, tyloxapol, ammonium chloride, salbutamol, albuterol, levosalbutamol, levalbuterol, pirbuterol, epinephrine, ephedrine, terbutaline, salmeterol, clenbuterol, formoterol, bambuerol, indacaterol, ephrinesulfate, ticlopidine, clopidogrel, prasugrel, ticagrelor, cilostazol, vorapaxar, trifusal, dipyridamole, a tocotrienol, and combinations thereof. In some embodiments, the one or more solid ingredients comprises aspirin. In some embodiments, the one or more solid ingredients comprises from about 81 mg to about 324 mg of aspirin. In some embodiments, the aspirin may be in an amount of about 10 mg to about 500 mg.
[0009] In some embodiments, the one or more solid ingredients comprises a statin. The statin may be selected from the group consisting of atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, and combinations thereof. The statin may be in an amount of about 1 mg to about 100 mg. In some embodiments, the statin may be in an amount of about 5 mg to about 40 mg. DESCRIPTION OF THE FIGURES
[0010] Figure 1 illustrates a cross-sectional view of a capsule of embodiments herein wherein the first (lower) compartment has a volume of about 423 mm3 and the second (upper) compartment has a volume of about 497 mm3, and wherein each compartment comprises a solid ingredient.
[0011] Figure 2 illustrates a cross-sectional view of a capsule of embodiments herein wherein the first (lower) compartment has a volume of about 743 mm3 and the second (upper) compartment has a volume of about 176 mm3, and wherein each compartment comprises a solid ingredient.
[0012] Figure 3 illustrates a cross-sectional view of a capsule of embodiments herein with a flattened bottom, wherein each compartment comprises a solid ingredient.
[0013] Figures 4A, 4B, and 4C illustrate standard and elongated TORPAC capsule sizes, which may be used in some embodiments described herein.
DETAILED DESCRIPTION
[0014] Before the present compositions and methods are described, it is to be understood that this invention is not limited to the particular processes, compositions, or methodologies described, as these may vary. It is also to be understood that the terminology used in the description is for the purpose of describing the particular versions or embodiments only, and is not intended to limit the scope of the present invention, which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present invention, the preferred methods, devices, and materials are now described. All publications mentioned herein are incorporated by reference in their entireties. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.
[0015] It must also be noted that as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to "an ingredient" is a reference to one or more ingredients and equivalents thereof known to those skilled in the art, and so forth. [0016] As used herein, the term "about" means plus or minus 10% of the numerical value of the number with which it is being used. Therefore, about 50 mg means in the range of 45 mg-55 mg.
[0017] The term "patient" or "subject" as used herein is an animal, particularly a human, suffering from an unwanted disease or condition that may be treated by the therapeutics and/or compositions described herein.
[0018] "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event occurs and instances where it does not.
[0019] Throughout the specification of the application, various terms are used such as "primary," "secondary," "first," "second," and the like. These terms are words of convenience used to distinguish between different elements, and such terms are not intended to limit how the different elements may be used.
[0020] As used herein, the term "medicament" or "therapeutic" means an agent used to treat, combat, ameliorate, prevent or improve an unwanted condition or disease of a subject.
[0021] A "therapeutically effective amount" or "effective amount" of a composition is an amount necessary or sufficient to achieve the desired result. The activity contemplated by the embodiments herein includes medically therapeutic, cosmetically therapeutic, and/or prophylactic treatment, as appropriate. A therapeutically effective amount of the compound of embodiments herein is typically an amount such that when it is administered in a physiologically tolerable excipient composition, it is sufficient to achieve an effective systemic concentration or local concentration in or on the tissue to achieve the desired therapeutic or clinical outcome.
[0022] The terms "treat," "treated," or "treating," as used herein, refer to therapeutic treatment, cosmetic treatment, and/or prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) an undesired physiological condition, disorder, or disease, or to obtain beneficial or desired clinical results. For the purposes of this invention, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms; diminishment of the extent of the condition, disorder, or disease; stabilization (i.e., not worsening) of the state of the condition, disorder, or disease; delay in onset or slowing of the progression of the condition, disorder, or disease; amelioration of the condition, disorder, or disease state; and remission (whether partial or total), whether detectable or undetectable, or enhancement or improvement of the condition, disorder, or disease. Treatment includes eliciting a clinically significant response without excessive levels of side effects.
[0023] As used herein, the term "consists of or "consisting of means that the formulation includes only the elements, steps, or ingredients specifically recited in the particular claimed embodiment or claim.
[0024] As used herein, the term "consisting essentially of or "consists essentially of means that the only active pharmaceutical ingredient in the formulation or method that treats the specified condition is the specifically recited therapeutic in the particular embodiment or claim.
[0025] Capsules are typically manufactured in certain standard sizes, such as TORPAC sizes, referred to as a capsule size designated by numerals, such as 000, 00, etc. Such capsules typically have two parts: a cap and a body, which are bonded or fitted together. One of the most common sizes is the 00 capsule. The typical size 00 capsule, in common with other capsules, has a standardized nominal volume. For instance, a size 00 capsule has a volume of approximately 0.95 milliliters. In some embodiments described below, the multicompartment capsule is a size 00 capsule. In some embodiments, the capsule size may be size 000, size 0, size 1, size 2, size 3, size 4, or size 5, or any non-standard size in between these sizes. In some embodiments described below, the capsule size may be elongated ("EL"), such that the size may be, for example, 00 EL. In some embodiments, the elongation may be to any standard length or to a non-standard length. . In some embodiments, the elongated capsule may add from about 50 mm3 to about 150 mm3 of additional volume to the first compartment, the second compartment, or a combination thereof. In some embodiments, the elongated capsule may add about 1 10 mm3 of additional volume to the first compartment, the second compartment, or a combination thereof. In some embodiments, if the diaphragm's diameter is reduced, it may be possible to insert a longer diaphragm into the capsule, thereby changing the available volumes in both the first and second compartments. In some embodiments, scaling the dimensions of the multi-compartment capsule described herein may result in a larger or smaller capsule with substantially the same ratios as described herein. In some embodiments, scaling the dimensions of the multi-compartment capsule described herein may result in a larger or smaller capsule with ratios different from those described herein.
[0026] For some applications, it may be advantageous to deliver one or more ingredients in the form of a capsule with two compartments. For some applications, it may advantageous for the one or more ingredients delivered in such a capsule to be solid ingredients. Exemplary benefits of such two compartment capsules may include increased compliance, a double chamber controlled release, increased efficacy or bioavailability of ingredients due to co-administration, increased stability, and the ability to formulate difficult combinations of ingredients into one capsule, such as incompatible actives which can now be co-administered.
[0027] Embodiments described herein are directed to a multi-compartment capsule comprising a body; a diaphragm, having two sidewalls and a bottom, extending into the body and defining a first compartment between an outer surface of the diaphragm and an inner surface of the body; and a cap mounted to an outer surface of the body and opposed to the diaphragm, and defining a second compartment between an inner surface of the diaphragm and the cap; wherein the two sidewalls of the diaphragm extend along the inner surface of the body and are aligned with an open end of the body. In some embodiments, the capsule is a size 00 capsule.
[0028] In some embodiments, the multi-compartment capsule may comprise a body; a diaphragm, having two sidewalls and a bottom, extending into the body and forming a first compartment defined by a first surface of the diaphragm and the body; and a cap mounted to the body and opposed to the diaphragm, the cap forming a second compartment defined by an opposing surface of the diaphragm and the cap; wherein the two sidewalls of the diaphragm extend along the inner surface of the body and are aligned with an open end of the body; and wherein the first compartment and the second compartment are each adapted to hold one or more solid ingredients. In some embodiments, the first compartment is hermetically sealed. In some embodiments, the one or more solid ingredients comprises a powder, a granule, a semi-solid, a microbead, a beadlet, or a combination thereof.
[0029] In some embodiments, the bottom of the diaphragm may be flattened. A flatter bottom may allow for more volume in the lower compartment. In some embodiments, the bottom of the diaphragm may be curved. In some embodiments, the bottom of the diaphragm may be substantially or partially flattened.
[0030] In some embodiments, the first compartment comprises a solid ingredient. In some embodiments, the second compartment comprises a solid ingredient. In some embodiments, the first compartment and second compartment each comprise one or more solid ingredients. In some embodiments, the first compartment and the second compartment each have sufficient volume to administer a therapeutically effective dose of one or more ingredients. [0031] In some embodiments, the first compartment may have a volume of about 50 mm3 to about 1000 mm3, and the second compartment may have a volume of about 50 mm3 to about 1000 mm3. For example, as shown in Figure 1, a capsule of an embodiment herein may have a first (lower) compartment having a volume of about 423 mm3 and a second (upper) compartment having a volume of about 497 mm3. In some embodiments, as shown in Figure 2, a capsule of an embodiment herein may have a the first (lower) compartment having a volume of about 743 mm3 and a second (upper) compartment having a volume of about 176 mm3.
[0032] In some embodiments, the one or more solid ingredients may be aspirin, a statin, a menstrual pain reliever, an agent for increasing bone density, an agent for relieving hot flashes, CoQIO, a cholesterol reducer, a thyroid hormone, a bronchodilator (e.g. ephedrine sulfate), an expectorant, a decongestant (e.g. pseudoephedrine or guaifenesin), an anti-inflammatory agent (e.g. an NSAID), a prebiotic, a probiotic, a digestive enzyme, a stool softener, anti-platelet aggregation agent, a vitamin (e.g. vitamin D3 or vitamin E), a pain reliever, an isoflavone derivative (e.g. ipriflavone), medicinal herbs (e.g. cohosh or castus), a corticosteroid (e.g. dexamethasone), proton pump inhibitor, any other solid pharmaceutical agent, or a combination thereof.
[0033] In some embodiments, the one or more solid ingredients comprises a probiotic. The probiotic may be selected from the group consisting of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus bulgaricus, Lactobacillus delbrueckii, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus salivarius, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus brevis, Lactobacillus breve, Streptococcus thermophilus, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium coagulans, Bifidobacterium breve, Bifidobacterium animalis, Bifidobacterium subtilis, Saccharomyces boulardi, and combinations thereof. In some embodiments, the one or more solid ingredients comprises from about 1 million colony forming units (CFUs) to about 100 billion CFUs of a probiotic. In some embodiments, the one or more solid ingredients may comprise, for example, about 1 million CFUs of a probiotic, 50 million CFUs of a probiotic, 100 million CFUs of a probiotic, 200 million CFUs of a probiotic, 300 million CFUs of a probiotic, 400 million CFUs of a probiotic, 500 million CFUs of a probiotic, 600 million CFUs of a probiotic, 700 million CFUs of a probiotic, 800 million CFUs of a probiotic, 900 million CFUs of a probiotic, 1 billion CFUs of a probiotic, about 2 billion CFUs of a probiotic, about 3 billion CFUs of a probiotic, about 4 billion CFUs of a probiotic, about 5 billion CFUs of a probiotic, about 6 billion CFUs of a probiotic, about 7 billion CFUs of a probiotic, about 8 billion CFUs of a probiotic, about 9 billion CFUs of a probiotic, about 10 billion CFUs of a probiotic, about 11 billion CFUs of a probiotic, about 12 billion CFUs of a probiotic, about 13 billion CFUs of a probiotic, about 14 billion CFUs of a probiotic, about 15 billion CFUs of a probiotic, about 20 billion CFUs of a probiotic, about 30 billion CFUs of a probiotic, about 40 billion CFUs of a probiotic, about 50 billion CFUs of a probiotic, about 60 billion CFUs of a probiotic, about 70 billion CFUs of a probiotic, about 80 billion CFUs of a probiotic, about 90 billion CFUs of a probiotic, about 100 billion CFUs of a probiotic, or any range between any of these values, including endpoints.
[0034] In some embodiments, the one or more solid ingredients comprises a digestive enzyme. The digestive enzyme may be selected from the group consisting of amylase, alpha-amylase, protease, alpha-galactosidase, beta-gulcanase, galactomannase, lactase, lipase, cellulase, hemicellulase, phytase, sucrase, invertase, pectinase, maltase, malt diastase, glucoamylase, xylanase, pullulanase, peptidase and dipeptidyl peptidase IV, serratia peptidase, lysozyme, bromelian, papain, and combinations thereof. In some embodiments, the one or more solid ingredients comprises from about 10 mg to about 10000 mg of a digestive enzyme. In some embodiments, the one or more solid ingredients may comprise, for example, about 10 mg of a digestive enzyme, about 20 mg of a digestive enzyme, about 30 mg of a digestive enzyme, about 40 mg of a digestive enzyme, about 50 mg of a digestive enzyme, about 60 mg of a digestive enzyme, about 70 mg of a digestive enzyme, about 80 mg of a digestive enzyme, about 90 mg of a digestive enzyme, about 100 mg of a digestive enzyme, about 200 mg of a digestive enzyme, about 300 mg of a digestive enzyme, about 400 mg of a digestive enzyme, about 500 mg of a digestive enzyme, about 600 mg of a digestive enzyme, about 700 mg of a digestive enzyme, about 800 mg of a digestive enzyme, about 900 mg of a digestive enzyme, about 1000 mg of a digestive enzyme, or any range between any of these values, including endpoints.
[0035] In some embodiments, the first compartment comprises from about one million CFUs to about 100 billion CFUs of a probiotic, and the second compartment comprises from about 10 mg to about 1000 mg of a digestive enzyme. In some embodiments, the first compartment comprises from about 10 mg to about 1000 mg of a digestive enzyme, and the second compartment comprises from about 1 million CFUs to about 100 billion CFUs of a probiotic. [0036] The compartment comprising the probiotic may have a volume of about 50 mm3 to about 1000 mm3, and the compartment comprising the digestive enzyme may have a volume of about 50 mm3 to about 1000 mm3.
[0037] In some embodiments, the one or more solid ingredients comprises a pharmaceutical agent. In some embodiments, the pharmaceutical agent is selected from, for example, aspirin, a statin, iprifiavone, cohosh, castus, coenzyme Q10 (CoQI O), guaifenesin, althea root, antimony pentasulfide, creosote, guaiacolsulfonate, ipecacuanha (syrup of ipecac), levoverbenone, potassium iodide, senega, tyloxapol, ammonium chloride, salbutamol, albuterol, levosalbutamol, levalbuterol, pseudoephedrine, dexamethasone, pirbuterol, epinephrine, ephedrine, terbutaline, salmeterol, clenbuterol, formoterol, bambuerol, indacaterol, ephrinesulfate, ticlopidine, clopidogrel, prasugrel, ticagrelor, cilostazol, vorapaxar, trifusal, dipyridamole, a tocotrienol, and combinations thereof.
[0038] In some embodiments, the one or more solid ingredients comprises aspirin. In some embodiments, the one or more solid ingredients comprises from about 10 mg to about 500 mg of aspirin. In some embodiments, the aspirin may be in an amount of about 50 mg to about 500 mg, about 100 mg to about 500 mg, about 150 mg to about 500 mg, about 200 mg to about 500 mg, about 50 mg to about 400 mg, about 100 mg to about 400 mg, about 150 mg to about 400 mg, about 200 mg to about 400 mg, or a range between any two of these values. In some embodiments, the aspirin comprises from about 81 mg to about 324mg. In some embodiments, one of the first or second compartment comprises aspirin and the other compartment may comprise a statin. In some embodiments, the statin may be in an amount of about 1 mg to about 100 mg, about 1 mg to about 50 mg, about 1 mg to about 30 mg, about 1 mg to about 20 mg, about 1 mg to about 10 mg, about 10 mg to about 100 mg, about 20 mg to about 100 mg, about 30 mg to about 100 mg, about 50 mg to about 100 mg, about 75 mg to about 100 mg, about 1 mg, about 10 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, or a range between any two of these values.
[0039] In some embodiments, the compartment comprising aspirin has a volume of about 50 mm3 to about 1000 mm3, and the other compartment has a volume of about 50 mm3 to about 1000 mm3.
[0040] In some embodiments, both compartments may comprise aspirin. For example, the first or second compartment may comprise about 300 mg of aspirin and the other compartment may comprise about 200 mg of aspirin. [0041] In some embodiments, the first or second compartment may comprise aspirin, while the other compartment may comprise a statin, a vitamin D3, or a combination thereof.
[0042] In some embodiments, the one or more solid ingredients may be a cholesterol reducer, a pain reliever, an anti-platelet aggregation agent, or a combination thereof.
[0043] In some embodiments, the first or second compartment may comprise aspirin, while the other compartment may comprise ipriflavone, cohosh, castus, or a combination thereof.
[0044] In some embodiments, the first or second compartment may comprise aspirin, while the other compartment may comprise pseudoephedrine, dexamethasone or a combination thereof. In some embodiments, the pseudoephedrine may be in an amount of about 10 mg to about 500 mg, about 50 mg to about 500 mg, about 100 mg to about 500 mg, about 150 mg to about 500 mg, about 200 mg to about 500 mg, about 50 mg to about 400 mg, about 100 mg to about 400 mg, about 150 mg to about 400 mg, about 200 mg to about 400 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 150 mg, about 200 mg, or a range between any two of these values. In some embodiments, the dexamethasone may be in an amount of about 5 mg to about 100 mg, about 5 mg to about 50 mg, about 10 mg to about 100 mg, about 10 mg to about 50 mg, about 5 mg to about 40 mg, about 10 mg to about 40 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, or a range between any two of these values. For example, the first or second compartment may comprise about 500 mg aspirin and the other compartment may comprise about 120 mg of pseudoephedrine and about 10 mg to about 40 mg of dexamethasone.
[0045] In some embodiments, the first or second compartment may comprise naproxen and the other compartment may comprise pseudoephedrine. In some embodiments, the naproxen is in an amount of about 10 mg to about 500 mg, about 50 mg to about 500 mg, about 100 mg to about 500 mg, about 150 mg to about 500 mg, about 200 mg to about 500 mg, about 50 mg to about 400 mg, about 100 mg to about 400 mg, about 150 mg to about 400 mg, about 200 mg to about 400 mg, about 50 mg to about 300 mg, about 100 mg to about 300 mg, about 150 mg to about 300 mg, about 200 mg to about 300 mg, about 50 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, or a range between any two of these values. For example, in some embodiments, the first or second compartment may comprise about 300 mg of naproxen and the other compartment may comprise about 120 mg of pseudoephedrine. In some embodiments, the first or second compartment may comprise aspirin and the other compartment may comprise a proton pump inhibitor. In some embodiments, the proton pump inhibitor may be selected from omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, esomeprazole, or a combination thereof. In some embodiments, the proton pump inhibitor may be in an amount of about 5 mg to about 100 mg, about 10 mg to about 100 mg, about 15 mg to about 100 mg, about 20 mg to about 100 mg, about 25 mg to about 100 mg, about 30 mg to about 100 mg, about 5 mg to about 50 mg, about 10 mg to about 50 mg, about 15 mg to about 50 mg, about 20 mg to about 50 mg, about 25 mg to about 50 mg, about 30 mg to about 50 mg, about 5 mg to about 30 mg, about 10 mg to about 30 mg, about 15 mg to about 30 mg, about 20 mg to about 30 mg, about 25 mg to about 30 mg, about 5 mg , about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, or a range between any two of these values. For example, in some embodiments, the first or second compartment may comprise about 500 mg aspirin and the other compartment may comprise about 30 mg of a proton pump inhibitor. In some embodiments, the one or more solid ingredients may be a menstrual pain reliever, an agent for increasing bone density, an agent for relieving hot flashes, or a combination thereof. In some embodiments, the first or second compartment may comprise a statin, and the other compartment may comprise CoQl O, aspirin, or a combination thereof. In some embodiments, the one or more solid ingredients may be a cholesterol reducer, CoQl O, or a combination thereof. In some embodiments, the first or second compartment may comprise guaifesnesin, and the other compartment may comprise ephrinesulfate. In some embodiments, the one or more solid ingredients include a bronchodilator and an expectorant. In some embodiments, the first or second compartment may comprise a prebiotic for gut health and a stool softener. In some embodiments, the first or second compartment may comprise a prebiotic and the other compartment may comprise docusate.
[0046] In some embodiments, the first or second compartment comprises aspirin and the other compartment comprises ticlopidine. In some embodiments, the one or more solid ingredients is an anti-platelet aggregation agent, aspirin, and a combination thereof. In some embodiments, the first or second compartment comprises aspirin and the second compartment comprises a tocotrienol. In some embodiments, the one or more solid ingredients is in powder or beadlet form.
[0047] In some embodiments, the one or more solid ingredients comprises a statin. The statin may be selected from the group consisting of atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, and combinations thereof. The statin may be in an amount of about 1 mg to about 100 mg. In some embodiments, the statin may be in an amount of about 1 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 100 mg, or a range between any two of these values. In some embodiments, the statin may be in an amount of about 5 mg to about 40 mg. In some embodiments, one of the first or second compartments comprises a statin in an amount of about 1 mg to about 100 mg. In some embodiments, the other compartment may comprise a second ingredient, such as, for example, aspirin, triiodothyronine, a statin, a probiotic, a digestive enzyme, or combinations thereof.
[0048] In some embodiments, the compartment comprising a statin has a volume of about 50 mm3 to about 1000 mm3, and the other compartment has a volume of about 50 mm3 to about 1000 mm3.
[0049] In some embodiments, the first compartment may comprise from about 10 mg to about 500 mg of aspirin, and the second compartment may comprise from about 10 mg to about 500 mg of ipriflavone, about 1 mg to about 150 mg of cohosh, about 10 mg to about 1000 mg of castus, or any combination thereof. In some embodiments the ipriflavone may be in an amount of about 10 mg to about 1000 mg. In some embodiments, the ipriflavone may be in an amount of about 50 mg, about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, or a range between any two of these values. In some embodiments the cohosh may be in an amount of about 1 mg to about 150 mg. In some embodiments, the cohosh may be in an amount of about 1 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 100 mg, about 150 mg, or a range between any two of these values. In some embodiments the castus may be in an amount of about 10 mg to about 1000 mg. In some embodiments, the castus may be in an amount of about 50 mg, about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, or a range between any two of these values.
[0050] In some embodiments, the first compartment may comprise from about 1 mg to about 100 mg of a statin, and the second compartment may comprise from about 10 mg to about 500 mg of aspirin, about 10 mg to about 1000 mg of CoQIO, or any combination thereof. In some embodiments the CoQ IO may be in an amount of about 10 mg to about 1000 mg. In some embodiments, the CoQI O may be in an amount of about 50 mg, about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, or a range between any two of these values. [0051] In some embodiments, the first compartment may comprise from about 10 mg to about 1200 mg of an expectorant, and the second compartment may comprise from about 5 mg to about 150 mg of a bronchodilator. In some embodiments the expectorant may be in an amount of about 10 mg to about 1000 mg. In some embodiments, the expectorant may be in an amount of about 50 mg, about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1 100 mg, about 1200mg, or a range between any two of these values. In some embodiments the bronchodilator may be in an amount of about 10 mg to about 150 mg. In some embodiments, the bronchodilator may be in an amount of about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 100 mg, about 150 mg, or a range between any two of these values. In some embodiments, the expectorant may be, for example, guaifenesin, althea root, antimony pentasulfide, creosote, guaiacolsulfonate, ipecacuanha (syrup of ipecac), levoverbenone, potassium iodide, senega, tyloxapol, ammonium chloride, or any combination thereof. In some embodiments, the bronchodilator may be, for example, salbutamol, albuterol, levosalbutamol, levalbuterol, pirbuterol, epinephrine, ephedrine, terbutaline, salmeterol, clenbuterol, formoterol, bambuerol, indacaterol, ephrinesulfate, or any combination thereof.
[0052] In some embodiments, the first or second compartment comprises a nonsteroidal anti-inflammatory drug (NSAID) and the other compartment comprises a proton pump inhibitor. In some embodiments the NSAID may be in an amount of about 10 mg to about 1000 mg. In some embodiments, the NSAID may be in an amount of about 50 mg, about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, or a range between any two of these values. In some embodiments, the NSAID may be selected from aspirin, ibuprofen, naproxen, diflunisal, salicylic acid and other salicylates, salsalate, dexibuprofen, fenoprofen, ketoprofen, dexketoprofen flurbiprofen, oxaprozin, loxoprofen, acetic acid derivatives, indomethacin, tolmetin, sulindac, etodolac, ketorolac, diclofenac, aceclofenac, nabumetone, enolic acid, piroxicam, meloxicam, tenoxicam, droxicam, lornoxicam, isoxicam, phenylbutazone, anthranilic acid derivatives, mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid, celecoxib, rofecoxib, valdecoxib, parecoxib, lumiracoxib, etoricoxib, firocoxib, sulfonanilides, nimesulide, clonixin, licofelone, H-harpagide, or a combination thereof.
[0053] In some embodiments, the first compartment may comprise from about 1 million CFUs to about 100 billion CFUs of a probiotic, and the second compartment may comprise from about 10 mg to about 500 mg of a stool softener. In some embodiments, the stool softener may be, for example, docusate.
[0054] In some embodiments, the first compartment may comprise from about 10 mg to about 500 mg of aspirin, and the second compartment may comprise from about 10 mg to about 500 mg of a platelet aggregation inhibitor. In some embodiments, the platelet aggregation inhibitor may be, for example, ticlopidine, clopidogrel, prasugrel, ticagrelor, cilostazol, vorapaxar, trifusal, dipyridamole, or any combination thereof.
[0055] In some embodiments, the first compartment may comprise from about 10 mg to about 500 mg of aspirin, and the second compartment may comprise from about 10 mg to about 500 mg of a form or derivative of vitamin E. In some embodiments, the form or derivative of vitamin E may be a tocotrienol, such as, for example, alpha tocotrienol, beta tocotrienol, gamma tocotrienol, delta tocotrienol, or any combination thereof.
[0056] Table 1 below lists some possible combinations of solid ingredients which may be found in some embodiments. It is to be understood that any of the ingredients within Table 1 may be found in any combination, and may be found in either compartment of the capsule described herein. It is to be further understood that the embodiments described in Table 1 are not meant to be limiting, but are merely illustrative.
TABLE 1
First compartment Second compartment
About 1 million to about 100 billion CFUs of About 10 mg to about 1000 mg of a digestive a probiotic enzyme
About 10 mg to about 500 mg of aspirin About 1 mg to about 100 mg of a statin
About 10 mg to about 500 mg of aspirin About 10 mg to about 500 mg of ipriflavone, and/or about 1 mg to about 150 mg of cohosh, and/or about 10 mg to about 1000 mg of castus
About 1 mg to about 100 mg of a statin About 10 mg to about 500 mg of aspirin
and/or about 10 mg to about 1000 mg of CoQIO
About 10 mg to about 1200 mg of an About 5 mg to about 150 mg of a
expectorant bronchodilator
About 1 million to about 100 billion CFUs of About 10 mg to about 500 mg of a stool a probiotic softener
About 10 mg to about 500 mg of aspirin About 10 mg to about 500 mg of a platelet aggregation inhibitor
About 10 mg to about 500 mg of aspirin About 10 mg to about 500 mg of a form or derivative of vitamin E
About 10 mg to about 500 mg of aspirin About 10 mg to about 500 mg of aspirin
About 10 mg to about 500 mg of aspirin About 10 mg to about 300 mg of pseudoephedrine; and/or About 10 mg to about 100 mg of dexmethylphenidate
About 10 mg to about 500 mg of naproxen About 10 mg to about 300 mg of pseudoephedrine
About 10 mg to about 500 mg of aspirin About 10 mg to about 100 mg of a proton pump inhibitor
About 10 mg to about 1000 mg of a nonAbout 10 mg to about 100 mg of a proton steroidal anti-inflammatory drug (NSAID) pump inhibitor
[0057] One skilled in the art would understand that the above examples are not meant to be limiting, but are illustrative of the types of ingredients that can be included in the compartments. In the examples above, the ingredient(s) in the first compartment may be in the second compartment, instead, and vice versa.
[0058] The method of making the type of multi-compartment capsule described herein differs from methods typically used in the art because in the present capsule, the diaphragm is bonded or fitted to the body of the capsule, effectuating a sealed compartment between the lower end of the body and the outer surface of the diaphragm, thus separating the first compartment from the second compartment and preventing leakage or spillage. Additionally, for example, in a typical capsule-in-capsule design, the outer capsule's dry ingredients cannot be displaced in order to make a place for an inner capsule. The inner capsule will simply sit on top of the powder and leave insufficient space for recapping, or worse, be crushed because of the powder's inability to be displaced. Further, the dosing of the powder in a typical capsule-in-capsule design (dose after capsule insertion) makes it extremely challenging to dose the powder between the sidewalls (especially with a size 1 capsule).
[0059] Table 2 below shows various dimensions of standard and elongated TORPAC capsule sizes, which may be used in some embodiments described herein.
TABLE 2
Figure imgf000016_0001
Figure imgf000017_0001
Recommended Storage Conditions: 59°-77°F / 15°-25°C RH 35-65%
[0060] Table 3 below shows additional dimensions of standard and elongated TORPAC capsule sizes, which may be used in some embodiments described herein.
Table 3
Figure imgf000017_0002
Body 8.18 20.22 0.107
0 305 475 680 0.68 21.70 Cap 7.65 10.72 0.107 96
Body 7.34 18.44 0.104
1 225 350 500 0.50 19.40 Cap 6.91 9.78 0.104 76
Body 6.63 16.61 0.102
2 165 260 370 0.37 18.00 Cap 6.35 8.94 0.102 61
Body 6.07 15.27 0.099
3 135 210 300 0.30 15.90 Cap 5.82 8.08 0.092 48
Body 5.56 13.59 0.890
4 95 145 210 0.21 14.30 Cap 5.31 7.21 0.096 38
Body 5.05 12.19 0.091
5 60 90 130 0.13 11.10 Cap 4.91 6.20 0.089 28
Body 4.68 9.32 0.086
[0061] Although the present invention has been described in considerable detail with reference to certain preferred embodiments thereof, other versions are possible. Therefore, the spirit and scope of the appended claims should not be limited to the description and the preferred versions contained within this specification. Modifications and improvements to the disclosed embodiments will be apparent to those skilled in the art in light of this disclosure, and are intended to fall within the scope of the pending claims.

Claims

A multi-compartment capsule comprising:
a body;
a diaphragm, having two sidewalls and a bottom, extending into the body and forming a first compartment defined by a first surface of the diaphragm and the body; and
a cap mounted to the body and opposed to the diaphragm, the cap forming a second compartment defined by an opposing surface of the diaphragm and the cap;
wherein the two sidewalls of the diaphragm extend along the inner surface of the body and are aligned with an open end of the body; and
wherein the first compartment and the second compartment are each adapted to hold one or more solid ingredients.
The capsule of claim 1, wherein the first compartment is hermetically sealed.
The capsule of claim 1, wherein the one or more solid ingredients comprises an aspirin, a statin, a menstrual pain reliever, an agent for increasing bone density, an agent for relieving hot flashes, CoQIO, a cholesterol reducer, a thyroid hormone, a bronchodilator, an expectorant, a decongestant, an anti-inflammatory agent, a prebiotic, a probiotic, a digestive enzyme, a stool softener, anti-platelet aggregation agent, a vitamin, a pain reliever, an isoflavone derivative, medicinal herbs, a corticosteroid, proton pump inhibitor, a solid pharmaceutical agent, or a combination thereof.
The capsule of claim 1, wherein the one or more solid ingredients comprises a powder.
The capsule of claim 1, wherein the one or more solid ingredients comprises a granule.
The capsule of claim 1, wherein the one or more solid ingredients comprises a probiotic.
The capsule of claim 6, wherein the probiotic is selected from the group consisting of selected from the group consisting of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus bulgaricus, Lactobacillus delbrueckii, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus salivarius, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus brevis, Lactobacillus breve, Streptococcus thermophilus, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium coagulans, Bifidobacterium breve, Bifidobacterium animalis, Bifidobacterium subtilis, Saccharomyces boulardi, and combinations thereof.
8. The capsule of claim 1 , wherein the one or more solid ingredients comprises from about 1 million colony forming units to about 100 billion colony forming units of a probiotic.
9. The capsule of claim 1 , wherein the one or more solid ingredients comprises a digestive enzyme.
10. The capsule of claim 9, wherein the digestive enzyme is selected from the group consisting of amylase, alpha-amylase, protease, alpha-galactosidase, beta-gulcanase, galactomannase, lactase, lipase, cellulase, hemicellulase, phytase, sucrase, invertase, pectinase, maltase, malt diastase, glucoamylase, xylanase, pullulanase, peptidase and dipeptidyl peptidase IV, serratia peptidase, lysozyme, bromelian, papain, and combinations thereof.
11. The capsule of claim 1 , wherein the one or more solid ingredients comprises from about 10 mg to about 1000 mg of a digestive enzyme.
12. The capsule of claim 1 , wherein the first compartment comprises from about 1 million colony forming units to about 100 billion colony forming units of a probiotic, and the second compartment comprises from about 10 mg to about 1000 mg of a digestive enzyme.
13. The capsule of claim 1 , wherein the first compartment comprises from about 10 mg to about 1000 mg of a digestive enzyme, and the second compartment comprises from about 1 million colony forming units to about 100 billion colony forming units of a probiotic.
14. The capsule of claim 1 , wherein the one or more solid ingredients comprises a pharmaceutical agent.
15. The capsule of claim 14, wherein the pharmaceutical agent is selected from selected from the group consisting of aspirin, a statin, ipriflavone, cohosh, castus, coenzyme Q10 (CoQIO), gauifenesin, althea root, antimony pentasulfide, creosote, guaiacolsulfonate, ipecacuanha (syrup of ipecac), levoverbenone, potassium iodide, senega, tyloxapol, ammonium chloride, salbutamol, albuterol, levosalbutamol, levalbuterol, pirbuterol, epinephrine, ephedrine, terbutaline, salmeterol, clenbuterol, formoterol, bambuerol, indacaterol, ephrinesulfate, ticlopidine, clopidogrel, prasugrel, ticagrelor, cilostazol, vorapaxar, trifusal, dipyridamole, a tocotrienol, and combinations thereof.
16. The capsule of claim 1, wherein the one or more solid ingredients comprises aspirin.
17. The capsule of claim 1 , wherein the one or more solid ingredients comprises from about 10 mg to about 500 mg of aspirin.
18. The capsule of claim 1, wherein the one or more solid ingredients comprises a statin.
19. The capsule of claim 18, wherein the statin is selected from the group consisting of atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, and combinations thereof.
20. The capsule of claim 1 , wherein the one or more solid ingredients comprises from about 1 mg to about 100 mg of a statin.
21. The capsule of claim 1 , wherein the one or more solid ingredients comprises a proton pump inhibitor.
22. The capsule of claim 1 , wherein the one or more solid ingredients comprises a nonsteroidal anti-inflammatory drug.
23. The capsule of claim 1 , wherein the one or more solid ingredients comprises coenzyme Q10.
24. The capsule of claim 1, wherein the one or more solid ingredients comprises an expectorant.
25. The capsule of claim 1 , wherein the one or more solid ingredients comprises a bronchodilator.
26. The capsule of claim 1, wherein the one or more solid ingredients comprises a stool softener.
27. The capsule of claim 1, wherein the one or more solid ingredients comprises a platelet aggregation inhibitor.
28. The capsule of claim 1 , wherein the one or more solid ingredients comprises vitamin E.
29. The capsule of claim 1 , wherein the one or more solid ingredients comprises vitamin D3.
30. The capsule of claim 1 , wherein the one or more solid ingredients is a powder, a granule, a semi-solid, a microbead, a beadlet, or a combination thereof.
PCT/US2016/056293 2015-10-09 2016-10-10 Capsule with internal diaphragm and solid ingredients WO2017062956A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CN201680071694.5A CN108366970A (en) 2015-10-09 2016-10-10 Capsule with internal spacer and solid constituent
EP16854537.4A EP3359140A4 (en) 2015-10-09 2016-10-10 Capsule with internal diaphragm and solid ingredients
US15/767,036 US11478429B2 (en) 2015-10-09 2016-10-10 Capsule with internal diaphragm and solid ingredients

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201562239454P 2015-10-09 2015-10-09
US201562239435P 2015-10-09 2015-10-09
US201562239442P 2015-10-09 2015-10-09
US62/239,435 2015-10-09
US62/239,454 2015-10-09
US62/239,442 2015-10-09

Publications (1)

Publication Number Publication Date
WO2017062956A1 true WO2017062956A1 (en) 2017-04-13

Family

ID=58488624

Family Applications (3)

Application Number Title Priority Date Filing Date
PCT/US2016/056293 WO2017062956A1 (en) 2015-10-09 2016-10-10 Capsule with internal diaphragm and solid ingredients
PCT/US2016/056276 WO2017062951A1 (en) 2015-10-09 2016-10-10 Capsule with volume-adjustable internal diaphragm
PCT/US2016/056285 WO2017062954A1 (en) 2015-10-09 2016-10-10 Capsule with internal diaphragm for improved bioavailability

Family Applications After (2)

Application Number Title Priority Date Filing Date
PCT/US2016/056276 WO2017062951A1 (en) 2015-10-09 2016-10-10 Capsule with volume-adjustable internal diaphragm
PCT/US2016/056285 WO2017062954A1 (en) 2015-10-09 2016-10-10 Capsule with internal diaphragm for improved bioavailability

Country Status (4)

Country Link
US (4) US11478429B2 (en)
EP (3) EP3359130A4 (en)
CN (3) CN108366959A (en)
WO (3) WO2017062956A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11160759B1 (en) 2015-10-09 2021-11-02 Combocap, Inc. Capsule with internal diaphragm for improved bioavailability

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10716761B2 (en) * 2017-07-24 2020-07-21 Alcresta Therapeutics, Inc. Ingestible medical delivery devices
GB2568238B (en) * 2017-11-01 2021-05-26 Sims Caroline Dietary powder composition comprising plant-based sources of fatty acids
EP3716955B1 (en) * 2017-12-01 2024-03-13 Healthy Option Consulting Inc. Soft dual chambered liquid-gel capsule and method to deliver sublingual and ingestible cannabis compositions
CN109337816A (en) * 2018-09-29 2019-02-15 昆明理工大学 A method of reducing molasses alcohol waste mash total nitrogen, total phosphorus and COD
US11547693B2 (en) * 2019-07-29 2023-01-10 Matthias Rath Ascorbate in the prevention of statin induced vascular calcification
CN110898027A (en) * 2019-12-12 2020-03-24 陕西鹤鸣健康科技有限公司 Vitamin K2 (MK-7) soft capsule for promoting calcium in blood to enter bone and preparation method thereof
CN114790379A (en) * 2022-04-24 2022-07-26 西南石油大学 Double-chamber microcapsule for drilling fluid and preparation method and application thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL7610038A (en) * 1976-09-09 1978-03-13 Tapanahony N V Multichambered capsule for therapeutically active substances - has chambers of different solubility with contents differing quantitatively and qualitatively
US20140212482A1 (en) * 2002-04-10 2014-07-31 Fred H. Miller Multi-phase, multi-compartment, capsular delivery apparatus and methods for using same
US20140302133A1 (en) * 2013-04-03 2014-10-09 Binutra, Inc. Capsule with internal diaphragm
WO2014202412A1 (en) * 2013-06-19 2014-12-24 Unilever Plc Multi-compartment water-soluble capsules
US20150246768A1 (en) * 2012-10-12 2015-09-03 Nestec S.A. Food capsule with multiple compartments

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1510260A (en) 1921-06-30 1924-09-30 Lloyd W Cyrenius Capsule
US3066501A (en) * 1958-12-04 1962-12-04 Chelton Hong Kong Ltd Stringless necklace beads having rigid bodies with resilient sockets therein
US3927195A (en) * 1974-01-31 1975-12-16 Lilly Industries Ltd Production of capsules
US4403461A (en) * 1980-02-29 1983-09-13 Automatisme Et Technique Device for sealing hard gelatin capsules and for packing a liquid product dose in the thus sealed capsule
US4339428A (en) 1980-08-18 1982-07-13 Bristol-Myers Company Capsule product containing high dosage of aspirin in powder or granulated form and alkaline tablet or pellet comprising magnesium carbonate, calcium carbonate and a magnesium dry component
JPS57156419A (en) * 1981-03-24 1982-09-27 Kyowa Chem Ind Co Ltd Remedy for sideropenia
JPS61100519A (en) * 1984-10-23 1986-05-19 Shin Etsu Chem Co Ltd Hard capsule for drug
US4748058A (en) * 1987-02-10 1988-05-31 Craig Jr Chester L Artificial tree
US5394980A (en) * 1987-06-30 1995-03-07 Tsai; Min H. Multicompartment mixing capsule
US5387421A (en) 1991-01-31 1995-02-07 Tsrl, Inc. Multi stage drug delivery system
US5223265A (en) 1992-01-10 1993-06-29 Alza Corporation Osmotic device with delayed activation of drug delivery
US5536506A (en) * 1995-02-24 1996-07-16 Sabinsa Corporation Use of piperine to increase the bioavailability of nutritional compounds
ITMI20020731A1 (en) 2002-04-08 2003-10-08 Ibsa Inst Biochimique Sa PHARMACEUTICAL COMPOSITIONS FOR ACETYLSALICYLIC ACID AND OMEGA-3 OILS
ES2774911T3 (en) * 2002-06-21 2020-07-23 Oreal Use of taurine or derivatives for the treatment of alopecia
TW200510002A (en) 2003-06-06 2005-03-16 Takeda Chemical Industries Ltd Solid pharmaceutical preparation
EP1675580A1 (en) * 2003-09-26 2006-07-05 Natural ASA Natural menaquinone 7 compositions
JP2006050933A (en) * 2004-08-11 2006-02-23 Meiji Riken Kk Chlorella dietary supplement
US8444681B2 (en) * 2009-06-15 2013-05-21 Roger P. Jackson Polyaxial bone anchor with pop-on shank, friction fit retainer and winged insert
MX2007006707A (en) * 2004-12-06 2008-01-16 Reliant Pharmaceuticals Inc Omega-3 fatty acids and dyslipidemic agent for lipid therapy.
EP1832282A1 (en) * 2004-12-28 2007-09-12 Qualicaps Co., Ltd. Band seal for hard capsule
JP5451065B2 (en) * 2005-04-19 2014-03-26 ヒルズ・ペット・ニュートリシャン・インコーポレーテッド Methods and compositions for prevention and treatment of kidney disease
WO2006130027A1 (en) * 2005-05-31 2006-12-07 Santos Ma Joyce Bedelia B Aqueous oral liquid vitamin supplements containing stabilized vitamin c and metal ions
US20070053869A1 (en) * 2005-09-02 2007-03-08 Yuichi Sugiyama Formulation and method for enhancement of gastrointestinal absorption of pharmaceutical agents
US8784886B2 (en) 2006-03-09 2014-07-22 GlaxoSmithKline, LLC Coating capsules with active pharmaceutical ingredients
US8491888B2 (en) * 2006-05-05 2013-07-23 Softgel Formulators, Inc. Highly absorbable coenzyme Q10 composition and method of producing same
JP5827784B2 (en) * 2006-07-14 2015-12-02 ナットファルマ エーエスエー Medicines and nutritional supplements containing vitamin K2
US20080213320A1 (en) 2007-03-01 2008-09-04 Jeremy B. Eisenstein Compositions for treatment of gastro-esophageal reflux disorders
US20090087483A1 (en) * 2007-09-27 2009-04-02 Sison Raymundo A Oral dosage combination pharmaceutical packaging
US8968717B2 (en) 2007-10-19 2015-03-03 Capsugel Belgium Nv Multi-compartmented container
GB2458467A (en) * 2008-03-18 2009-09-23 Ajit Lalvani Dietary supplement for maintenance of bone health
US20120209339A1 (en) * 2011-02-11 2012-08-16 Daniel Scodary Device for spinal fusion
US9168308B2 (en) * 2011-04-22 2015-10-27 Paul Joseph FAERSTEIN Compositions and methods for nutritional supplementation
EP3069708B1 (en) * 2011-10-06 2018-05-09 Combocap, Inc. Capsule
EP2968081A4 (en) * 2013-03-15 2016-08-10 Banner Life Sciences Llc Non-gelatin enteric soft capsules
US9139458B2 (en) * 2013-03-15 2015-09-22 Janet Angel Compositions and methods of use
EP2777802B1 (en) * 2013-12-03 2016-03-16 Capsugel Belgium NV Multi-compartment dosage form articles
WO2017062956A1 (en) 2015-10-09 2017-04-13 Binutra Incorporated Capsule with internal diaphragm and solid ingredients

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL7610038A (en) * 1976-09-09 1978-03-13 Tapanahony N V Multichambered capsule for therapeutically active substances - has chambers of different solubility with contents differing quantitatively and qualitatively
US20140212482A1 (en) * 2002-04-10 2014-07-31 Fred H. Miller Multi-phase, multi-compartment, capsular delivery apparatus and methods for using same
US20150246768A1 (en) * 2012-10-12 2015-09-03 Nestec S.A. Food capsule with multiple compartments
US20140302133A1 (en) * 2013-04-03 2014-10-09 Binutra, Inc. Capsule with internal diaphragm
WO2014202412A1 (en) * 2013-06-19 2014-12-24 Unilever Plc Multi-compartment water-soluble capsules

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3359140A4 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11160759B1 (en) 2015-10-09 2021-11-02 Combocap, Inc. Capsule with internal diaphragm for improved bioavailability
US11357732B2 (en) 2015-10-09 2022-06-14 Combocap, Inc. Capsule with volume-adjustable internal diaphragm
US11478429B2 (en) 2015-10-09 2022-10-25 Combocap, Inc. Capsule with internal diaphragm and solid ingredients

Also Published As

Publication number Publication date
WO2017062954A1 (en) 2017-04-13
US11160759B1 (en) 2021-11-02
EP3359140A4 (en) 2019-05-01
US20220160641A1 (en) 2022-05-26
US20180289625A1 (en) 2018-10-11
CN108472244A (en) 2018-08-31
EP3359130A4 (en) 2019-05-01
EP3359131A1 (en) 2018-08-15
CN108366970A (en) 2018-08-03
EP3359130A1 (en) 2018-08-15
US11357732B2 (en) 2022-06-14
EP3359131A4 (en) 2019-05-01
CN108366959A (en) 2018-08-03
US20180296489A1 (en) 2018-10-18
WO2017062951A1 (en) 2017-04-13
EP3359140A1 (en) 2018-08-15
US11478429B2 (en) 2022-10-25

Similar Documents

Publication Publication Date Title
US11478429B2 (en) Capsule with internal diaphragm and solid ingredients
AU2012363788B2 (en) Delayed-release formulation for reducing the frequency of urination and method of use thereof
CN111031996B (en) Dual release dosage form capsule and method, apparatus and system for making same
AU2013235518B2 (en) Extended-release formulation for reducing the frequency of urination and method of use thereof
Emerson et al. Dexlansoprazole: a proton pump inhibitor with a dual delayed-release system
JP2018526403A5 (en)
CN107335057A (en) For alleviating the pharmaceutical preparation and its application method of frequent micturition
CN108391420A (en) Composition and its preparation method and application for reducing micturition frequency
JP2022552510A (en) gastrointestinal health composition
TW201206782A (en) Dispensing container with enhanced plugging means
EP2612662B1 (en) Delayed-release formulation for reducing the frequency of urination and method of use thereof
EP2612661B1 (en) Delayed release formulation for reducing the frequency of urination and method of use thereof
WO2017039833A1 (en) Delayed-release formulations, methods of making and use thereof

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16854537

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2016854537

Country of ref document: EP