WO1994004138A1 - Sustained release tablets containing bupropion - Google Patents

Sustained release tablets containing bupropion Download PDF

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Publication number
WO1994004138A1
WO1994004138A1 PCT/GB1993/001722 GB9301722W WO9404138A1 WO 1994004138 A1 WO1994004138 A1 WO 1994004138A1 GB 9301722 W GB9301722 W GB 9301722W WO 9404138 A1 WO9404138 A1 WO 9404138A1
Authority
WO
WIPO (PCT)
Prior art keywords
hydrochloride
sustained release
bupropion
bupropion hydrochloride
release tablet
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/GB1993/001722
Other languages
English (en)
French (fr)
Inventor
Jennie Sue Galloway Ludwig
Joel Elmore Sutton, Jr.
William Leroy Bass, Jr.
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wellcome Foundation Ltd
Original Assignee
Wellcome Foundation Ltd
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=10720358&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO1994004138(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to EP93918020A priority Critical patent/EP0656775B1/en
Priority to AU47258/93A priority patent/AU677595B2/en
Priority to JP6506019A priority patent/JPH08500110A/ja
Priority to KR1019950700497A priority patent/KR100294154B1/ko
Priority to CA002142320A priority patent/CA2142320C/en
Application filed by Wellcome Foundation Ltd filed Critical Wellcome Foundation Ltd
Priority to HK98103254A priority patent/HK1004323A1/en
Priority to DE69316015T priority patent/DE69316015T2/de
Publication of WO1994004138A1 publication Critical patent/WO1994004138A1/en
Anticipated expiration legal-status Critical
Priority to GR970403389T priority patent/GR3025794T3/el
Priority to LU90656C priority patent/LU90656I2/fr
Ceased legal-status Critical Current

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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids

Definitions

  • Bupropion hydrochloride is a marketed antidepressant. It is chemically known as (+)-2-(tert-butyiamino)-3'-chloropropiophenone hydrochloride. (See U.S. Patents 3.819.706 and 3.885.046). Also see Merck Index. Eleventh Edition, entry No. 1488.
  • bupropion hydrochloride is sold in the form of an instant release tablet wherein greater than 75% of bupropion hydrochloride is released from the tablet dissolution media in 45 minutes (See 1993 Physicians Desk Reference (PDR). pages 842 to 844).
  • PDR Physicians Desk Reference
  • the PDR indicates bupropion hydrochloride as presently sold in an instant release tablet as being associated with seizures in approximately 0.4% (4/1000) patients treated at doses of up to 450 mg per day. In studies to date, the risk of seizures seem to be strongly associated, in part, with use of instant release tablets.
  • the present invention provides an improved product in that it provides sustained release of the active ingredient as well as ease of manufacture over that disclosed in U.S. Patent 4,687.660.
  • SR sustained release
  • the present invention is now able to provide a controlled sustained release, sometimes also referred to as a sustained release (SR) tablet with improved properties and which has a shelf life over one year (i.e., there is less than 10% loss most preferably less than about 5% loss (breakdown), of buproprion hydrochloride) in one year of storage at room temperature 15 to 25°C (59 to 77°F) at 35 to 60% relative humidity.
  • SR sustained release
  • the tablet will preferably contain no less than about 95mg of bupropion hydrochloride after one year in storage (shelf life).
  • tabiet includes the term "caplet". which is the word used to describe a tablet termed substantially in the shape of a capsule.
  • the oral administration of the controlled release tablets of this invention to treat depression in humans will be under the jurisdiction of the physician: however, tablets for a 75kg ( 150 pound) human will ordinarily be given one to three times per day to provide a total daily dosage of 100 to 450mg per day for a time period that the human patient requires same as determined by a physician.
  • the tablets are swallowed by the human in the normal manner with the aid of water or other liquid.
  • the tablets herein preferably have a round biconvex shape (which is preferred): however, this may be varied depending on the creativity of the tablet designer. With the tablets of this invention it is now possible to dose one or two times per day rather than the three times a day as presently done with the currently marketed product.
  • the present invention provides a sustained release tablet comprising bupropion hydrochloride and hydroxypropyl methylcellulose.
  • the amount of hydroxypropyl methylcellulose to the amount of bupropion hydrochloride being from 0.19: 1 to 1.1 :1 respectively and the tablet being capable in water of releasing from 20 to 60 percent of the total amount of bupropion hydrochloride in 1 hour, from 50 to 95 percent of the total amount of bupropion hydrochloride in 4 hours and not less than 75 percent of the total amount of bupropion hydrochloride in 8 hours.
  • Cysteine hydrochloride or glycine hydrochloride may also be included. Cysteine hydrochloride is more preferable than glycine hydrochloride. since it unexpectedly causes less discoloration to the tablet core.
  • the amount of bupropion hydrochloride in each tablet is typically from 25mg to 500mg, with the tablet dose being more typically 50mg, lOOmg or 150mg.
  • Methocel is the brand name for hydroxypropyl methylcellulose (HPMC) from Dow Chemical. Other companies also supply HPMC.
  • HPMC hydroxypropyl methylcellulose
  • Fig. 1 is a top view of the preferred tablet shape of this invention:
  • Fig. 2 is a side view of the tablet of Fig. 1 :
  • Fig. 3 is a sectional view taken along line 3-3 in Fig. 1 :
  • Fig. 4 is a graph showing plasma bupropion (as the free base) concentrations in nanograms/ml in adult male humans following a single dose of two 50mg bupropion HC1 (SR) tablets, divided by two over 24 hours from time of administration provided by the 50mg tablet example of this invention:
  • Fig. 5 is a graph showing plasma bupropion (as the free base ) . concentrations in nanograms/ml in adult male humans following a single dose of one 1 OOmg bupropion HC1 (SR) tablets over 24 hours provided by the lOOmg tablet example of this invention: and
  • Fig. 6 is a graph showing plasma bupropion (as the free base) concentrations in nanograms/ml in adult male humans following a single 150mg tablet over 24 hours provided by the 150mg (SR) tablet example of this invention.
  • particles of bupropion hydrochloride are preferably blended with microcrystalline cellulose and hydroxypropyl methylcellulose (Methocel) to form an admixture of blended powders.
  • a 20 mesh sieve is conveniently used to screen the bupropion hydrochloride particles, cellulose particles and hydroxypropyl methylcellulose particles prior to blending the ingredients.
  • the cysteine hydrochloride or glycine hydrochloride is dissolved in water to form a granulating solution. Thereafter, the granulating solution is preferably sprayed onto the blended powders, which are then dried.
  • a lubricant such as magnesium stearate is added and intermixed (blended) with the blended powders having the granulating solution dried thereon.
  • suitable fillers include the following: lactose, starch.
  • Microcrystalline cellulose is also preferably added to the product to provide compressibility. Compression of the mixture in a punch and die is then used to form the tablet core.
  • the tablet (sometimes referred to as the core ) is preferably film coated with a colored coating such as a Opadry Purple. Opadry Blue or Opadry White for identification, taste masking, and appearance purposes to provide a film coated tablet.
  • the film coating does not substantially affect the release rate of the bupropion hydrochloride from the tablet, since the coating is instant release which rapidly dissolves in the stomach.
  • the outer film coating is typically 0.03mm to 0.10mm in thickness.
  • the amount of hydroxypropyl methylcellulose is 0.19 to 1.1 and more preferably 0.26 to 0.68 parts by weight and the amount of cysteine hydrochloride or giycine hydrochloride is 0.02 to 0.27 and more preferably 0.05 to 0.16 parts by weight.
  • the amount of hydroxypropyl methylcellulose is I9mg to 1 lOmg and most preferably 26.7 to 68mg and the amount of cysteine hydrochloride or glycine hydrochloride is 2.7mg to 27mg and most preferably 5mg to 16.2mg.
  • the surface area to volume of the non film-coated or core po ⁇ ion of the tablets herein is important in maintaining the appropriate controlled sustained release rates.
  • the ratio of the surface area of the non film coated tablet (sometimes referred to as the core) surface area to tablet volume is preferably 3: 1 to 25: lcm' ⁇ and more preferably 7:1 to 16:lcm ⁇ l for tablets of 50. 100 and 150mg bupropion hydrochloride content.
  • the ratio of the tablet surface area to tablet volume is most preferably 13: 1 to 16: lcm" ⁇ and for the lOOmg bupropion HC1 content tablet the ratio is most preferably 9: 1 to 12: lcm"l and for the 150mg bupropion HC1 content tablet the ratio is most preferably 7:1 to 10: 1 cm" - .
  • the release rate of bupropion hydrochloride from the sustained release (SR) tablets disclosed (whether or not film coated) herein in distilled water is preferably as follows:
  • the release rate of bupropion HC1 is preferably 30 to 50%) in 1 hour. 70 to 95% in 4 hours and not less than 80% in 8 hours.
  • the release rate is preferably 25 to 45%) in 1 hour. 60 to 85%) in 4 hours and not less than 80% in 8 hours.
  • the release rate is preferably 25 to 45% in 1 hour. 60 to 75% in 4 hours and not less than 85% in 8 hours.
  • test conditions and apparatus to determine the drug release (dissolution) rates of buproprion hydrochloride are as follows:
  • Sample Size a single unweighted tablet per vessel
  • test for dissolution is performed as specified below in the U.S. Pharmacopoeia under "Drug Release” and the medium is sampled at 1. 4 and 8 hours.
  • Sample Preparation Withdraw a measured portion of the dissolution medium not to exceed 10ml at each sampling point without replacement. Filter the sample through a LID X GMF 0.45 micron filter or a Zymark 10 micron filter (or equivalent).
  • Svstem Suitability Test Replicate injections of the Standard Preparation give relative standard deviations for peak retention times and peak responses no greater than 2 percent.
  • the tailing factor (T.USP) for the bupropion peak is not greater than 2.5.
  • Ph 7.0 Phosphate Buffer Preparation Transfer 27.22g of monobasic potassium phosphate into a 1000-ml volumetric flask. Dissolve in and dilute to volume with water and mix. Transfer 250ml of this solution into a 1000-ml of 0.291 M sodium hydroxide, dilute to volume with water and mix.
  • Step II Sampling Volume Corrections
  • n number of previous samples taken
  • v volume of sampie taken each time
  • the tablet also preferably includes as other ingredients, e.g.. lubricating agents for ease in manufacture and fillers for ease of manufacturing and to bulk the tablet to provide the desired size.
  • lubricating agents for ease in manufacture and fillers for ease of manufacturing and to bulk the tablet to provide the desired size.
  • the tablet is also preferably coated with an instant release coating for appearance, taste masking, and product identification e.g. Opadry Purple. Blue or White, which will dissolve in the stomach and not substantially affect bupropion hydrochloride release rates and bupropion hydrochloride stability.
  • an instant release coating for appearance, taste masking, and product identification e.g. Opadry Purple. Blue or White, which will dissolve in the stomach and not substantially affect bupropion hydrochloride release rates and bupropion hydrochloride stability.
  • the preferred nominal viscosity of 2% solution in water is not less than 3.000 centipoise and not more than 5.600 centipoise. It is supplied by Dow Chemical Company. Midland. MI as Methocei E4M premium CR.
  • Opadry ⁇ Purple YS- 1-4845 is supplied by Colorcon. Inc.. contains FD&C Red No. 40 aluminum lake, hydroxypropyl methycellulose. titanium dioxide, polyethylene glycol. olysorbate 80. and FD&C Blue No. 2 Aluminum Lake.
  • OpadryR Blue YS- 1-4282 is supplied Colorcon. Inc.. contains FD&C Blue No. 1 aluminum lake, hydroxypropyl methycellulose. titanium dioxide, polyethylene glycol. and polysorbate 80.
  • OpadryR White YS-1-7059 is supplied by Colorcon. Inc.. contains hydroxypropyl methylcellulose. titanium dioxide, and polyethylene glycol. Reference should now be had to Figs. 1 to 3 for a description of the preferred form of the biconvex film coated tablets of this invention which contain as the active ingredient (drug) 50mg. lOOmg or 150mg of bupropion HC1.
  • the tablet (core) is shown at 10 and the film coating is shown at 1 1 in Fig.3
  • Figs. 4. 5 and 6 which illustrate plasma bupropion levels, as the free base i.e. the compound bupropion itself (see the Merck Index. Eleventh Edition entry No. 1488) after oral administration to adult males (humans) of 50mg, lOOmg and 150mg bupropion HC1 film coated tablets of the examples herein. It is to be understood that because of the naure of the film coating, the release rate will be substantially the same whether or not the tablets are film-coated and. therefore, the data is also representative of non film coated tablets disclosed herein.
  • Fig. 4 represents plasma levels (divided by 2) of bupropion after oral dosage with two 50mg SR tablets in 21 male (human) patients 18 to 40 years of age weighing 66 to 92kg (132 to 1841bs).
  • the maximum level shown is detected in the blood plasma at least one of the patients and the minimum being that detected in the blood plasma at least one of the patients and the mean being the average of all measurements of all participants.
  • the bupropion plasma levels for the 50mg tablet dosing measured over 24 hours as in this figure were done as described in the radioimmunoassay test set forth in the article Radioimmunoassay And Pharmacokinetic Profile of Bupropion In The Dog by Robert F. Butz t al. published in the Joumai of Pharmacology and Experimental Therapeutics. Vol. 217. No. 3 (1981 ).
  • Fig. 5 is a repeat with respect to Fig. 4: however a single oral dose of a lOOmg SR tablet of this disclosure's example was administered to the same group of males as those tested previously in Fig. 4: however, the bupropion plasma levels were not divided in two. The plasma levels were also measured at the time intervals shown using the test procedure described in the aforementioned Butz et al. article.
  • Fig. 6 represents oral dosing of 24 male (human) patients, ages 20 to 39 years, weight 68 to 98kg (136 to 1961bs). Each of the males was dosed once with a 150mg bupropion HC1 SR tablet and bupropion plasma level measurements were made as shown on the piot of Fig. 6 at the time intervals shown to arrive at the maximum, minimum for any patient and the mean (average) for all patients in the test.
  • Coating thickness* 0.05 - 0.10mm for all tablets of the examples.
  • Bupropion Hydrochloride Sustained-Release Tablets 150mg Bupropion Hydrochloride per coated Tablet.
  • Bupropion Hydrochloride Sustained-Release Tablets lOOmg Bupropion Hydrochloride Per Coated Tablet.
  • Step 3 Spray the solution from Step 2 onto the blended powders from Step 1 using a fluid bed granuiator. Additional purified water may be used, if necessary, to obtain proper granule wetness.
  • Bupropion Hydrochloride Microcrystalline Cellulose NF Hydroxypropyl Methylcellulose 2910. USP Cysteine Hydrochloride. USP Magnesium Stearate. NF
  • bupropion hydrochloride microcrystalline cellulose hydroxypropyl methylcellulose
  • Step 3 Spray the solution from Step 2 onto the blended powders from Step 1 using a fluid bed granuiator. Additional purified water may be used, if necessary, to obtain proper granule wetness.

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  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • General Preparation And Processing Of Foods (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PCT/GB1993/001722 1992-08-14 1993-08-13 Sustained release tablets containing bupropion Ceased WO1994004138A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
DE69316015T DE69316015T2 (de) 1992-08-14 1993-08-13 Tabletten mit verzögerter wirkstoffabgabe enthaltend bupropion
AU47258/93A AU677595B2 (en) 1992-08-14 1993-08-13 Sustained release tablets containing bupropion
JP6506019A JPH08500110A (ja) 1992-08-14 1993-08-13 ブプロピオン含有持続放出型錠剤
KR1019950700497A KR100294154B1 (ko) 1992-08-14 1993-08-13 부프로피온함유서방형정제
CA002142320A CA2142320C (en) 1992-08-14 1993-08-13 Sustained release tablets containing bupropion
EP93918020A EP0656775B1 (en) 1992-08-14 1993-08-13 Sustained release tablets containing bupropion
HK98103254A HK1004323A1 (en) 1992-08-14 1993-08-13 Sustained release tablets containing bupropion
GR970403389T GR3025794T3 (en) 1992-08-14 1997-12-30 Sustained release tablets containing bupropion.
LU90656C LU90656I2 (fr) 1992-08-14 2000-10-18 Hydrochlorure de bupropion

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB929217295A GB9217295D0 (en) 1992-08-14 1992-08-14 Controlled released tablets
GB9217295.6 1992-08-14

Publications (1)

Publication Number Publication Date
WO1994004138A1 true WO1994004138A1 (en) 1994-03-03

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PCT/GB1993/001722 Ceased WO1994004138A1 (en) 1992-08-14 1993-08-13 Sustained release tablets containing bupropion

Country Status (21)

Country Link
US (1) US5427798A (https=)
EP (1) EP0656775B1 (https=)
JP (1) JPH08500110A (https=)
KR (1) KR100294154B1 (https=)
AT (1) ATE161422T1 (https=)
AU (1) AU677595B2 (https=)
CA (1) CA2142320C (https=)
CY (1) CY2143B1 (https=)
DE (1) DE69316015T2 (https=)
ES (1) ES2111168T3 (https=)
GB (1) GB9217295D0 (https=)
GR (1) GR3025794T3 (https=)
HK (1) HK1004323A1 (https=)
IL (1) IL106693A (https=)
LU (1) LU90656I2 (https=)
MX (1) MX9304967A (https=)
NZ (1) NZ254947A (https=)
SG (1) SG43911A1 (https=)
TW (1) TW260607B (https=)
WO (1) WO1994004138A1 (https=)
ZA (1) ZA935942B (https=)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995003791A1 (en) * 1993-07-30 1995-02-09 The Wellcome Foundation Limited Stabilized pharmaceutical composition containing bupropion
US5541231A (en) * 1993-07-30 1996-07-30 Glaxo Wellcome Inc. Stabilized Pharmaceutical
WO1999038503A1 (en) * 1998-01-29 1999-08-05 Sepracor Inc. Pharmacological uses of optically pure (+)-bupropion
WO1999038502A1 (en) * 1998-01-29 1999-08-05 Sepracor Inc. Pharmaceutical uses of optically pure (+)-bupropion
WO1999038504A1 (en) * 1998-01-29 1999-08-05 Sepracor Inc. Pharmaceutical uses of optically pure (-)-bupropion
WO1999038499A3 (en) * 1998-01-29 1999-09-30 Sepracor Inc Methods and compositions for aiding in smoking cessation and for treating pain and other disorders using optically pure (-)-bupropion
US6337328B1 (en) 1999-03-01 2002-01-08 Sepracor, Inc. Bupropion metabolites and methods of use
US6342496B1 (en) 1999-03-01 2002-01-29 Sepracor Inc. Bupropion metabolites and methods of use
EP1275383A1 (en) * 2001-07-09 2003-01-15 Valpharma S.A. Modified release pharmaceutical composition containing Bupropion HCI as active substance
US6734213B2 (en) 1999-01-20 2004-05-11 Smithkline Beecham Corporation Pharmaceutically active morpholinol
US6855820B2 (en) 1999-01-20 2005-02-15 Smithkline Beecham Corporation Pharmaceutically active morpholinol
US6998400B2 (en) 1998-01-22 2006-02-14 Smithkline Beecham Corporation Pharmaceutically active morpholinol
US7098206B2 (en) 1998-01-21 2006-08-29 Smithkline Beecham Corporation Pharmaceutically active morpholinol

Families Citing this family (217)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5616344A (en) * 1994-06-14 1997-04-01 Fuisz Technologies Ltd. Apparatus and process for strengthening low density compression dosage units and product therefrom
CN1623533A (zh) * 1997-09-25 2005-06-08 拜尔公司 控释活性化合物的药物制剂
US5968553A (en) * 1997-12-30 1999-10-19 American Home Products Corporation Pharmaceutical composition containing bupropion hydrochloride and an inorganic acid stabilizer
US6221917B1 (en) 1997-12-30 2001-04-24 American Home Products Corporation Pharmaceutical composition containing bupropion hydrochloride and a stabilizer
US6150420A (en) * 1998-06-01 2000-11-21 Theramax, Inc. Method for enhanced brain delivery of bupropion
US6153223A (en) * 1998-06-05 2000-11-28 Watson Pharmaceuticals, Inc. Stabilized pharmaceutical compositions
US6096341A (en) * 1998-10-30 2000-08-01 Pharma Pass Llc Delayed release tablet of bupropion hydrochloride
US6033686A (en) * 1998-10-30 2000-03-07 Pharma Pass Llc Controlled release tablet of bupropion hydrochloride
US6238697B1 (en) * 1998-12-21 2001-05-29 Pharmalogix, Inc. Methods and formulations for making bupropion hydrochloride tablets using direct compression
US6589553B2 (en) * 2001-02-08 2003-07-08 Andrx Pharmaceuticals, Inc. Controlled release oral dosage form
US6210716B1 (en) * 1999-02-26 2001-04-03 Andrx Pharmaceuticals, Inc. Controlled release bupropion formulation
US8545880B2 (en) * 1999-02-26 2013-10-01 Andrx Pharmaceuticals, Llc Controlled release oral dosage form
USD430285S (en) * 1999-04-16 2000-08-29 Merck & Co., Inc. Tablet
US6280763B1 (en) 1999-05-10 2001-08-28 Pierce Management, Llc Apparatus and method for transdermal delivery of bupropion
CA2389236A1 (en) * 1999-11-02 2001-05-10 Depomed, Inc. Pharmacological inducement of the fed mode for enhanced drug administration to the stomach
US6306436B1 (en) 2000-04-28 2001-10-23 Teva Pharmaceuticals Usa, Inc. Stabilized, acid-free formulation for sustained release of bupropion hydrochloride
CA2433915C (en) * 2001-02-08 2010-04-20 Andrx Pharmaceuticals, Inc. Improved controlled release oral dosage form
US20030044462A1 (en) * 2001-08-20 2003-03-06 Kali Laboratories, Inc. Sustained release tablets containing bupropion hydrochloride
EP2316468A1 (en) 2002-02-22 2011-05-04 Shire LLC Delivery system and methods for protecting and administering dextroamphetamine
EP3173082A1 (en) * 2002-05-17 2017-05-31 Duke University Method for treating obesity
US20050215552A1 (en) * 2002-05-17 2005-09-29 Gadde Kishore M Method for treating obesity
US7776314B2 (en) 2002-06-17 2010-08-17 Grunenthal Gmbh Abuse-proofed dosage system
AU2003284942A1 (en) * 2002-10-30 2004-06-07 Pharmacia Corporation Oral extended release tablets and methods of making and using the same
US20040096497A1 (en) * 2002-11-19 2004-05-20 Ponder Garratt W. Methods of providing controlled-release pharmaceutical compositions and controlled-release pharmaceutical compositions
US6893660B2 (en) * 2002-11-21 2005-05-17 Andrx Pharmaceuticals, Inc. Stable pharmaceutical compositions without a stabilizer
EP1617832B1 (en) * 2003-04-29 2008-03-12 Orexigen Therapeutics, Inc. Compositions for affecting weight loss
US8075872B2 (en) * 2003-08-06 2011-12-13 Gruenenthal Gmbh Abuse-proofed dosage form
DE10361596A1 (de) 2003-12-24 2005-09-29 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
DE102005005446A1 (de) 2005-02-04 2006-08-10 Grünenthal GmbH Bruchfeste Darreichungsformen mit retardierter Freisetzung
US20070048228A1 (en) 2003-08-06 2007-03-01 Elisabeth Arkenau-Maric Abuse-proofed dosage form
DE10336400A1 (de) 2003-08-06 2005-03-24 Grünenthal GmbH Gegen Missbrauch gesicherte Darreichungsform
DE102004032051A1 (de) * 2004-07-01 2006-01-19 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten, festen Darreichungsform
ME00391B (me) * 2003-08-08 2011-10-10 Biovail Laboratories Int Srl Tableta bupropion hidrohlorida sa modifikovanim otpuštanjem
KR20060128995A (ko) 2004-01-13 2006-12-14 듀크 유니버시티 체중감량에 영향을 미치는 항경련제와 항정신병 약물의조성물
US20060160750A1 (en) * 2004-01-13 2006-07-20 Krishnan K R R Compositions of an anticonvulsant and an antipsychotic drug and methods of using the same for affecting weight loss
US7713959B2 (en) * 2004-01-13 2010-05-11 Duke University Compositions of an anticonvulsant and mirtazapine to prevent weight gain
US20060100205A1 (en) * 2004-04-21 2006-05-11 Eckard Weber Compositions for affecting weight loss
DE102004032049A1 (de) 2004-07-01 2006-01-19 Grünenthal GmbH Gegen Missbrauch gesicherte, orale Darreichungsform
USD515202S1 (en) 2004-07-19 2006-02-14 Merck & Co., Inc Tablet
US8586085B2 (en) 2004-11-08 2013-11-19 Biokey, Inc. Methods and formulations for making pharmaceutical compositions containing bupropion
US20060099262A1 (en) * 2004-11-08 2006-05-11 Biokey, Inc. Methods and formulations for making controlled release oral dosage form
GB0425445D0 (en) * 2004-11-18 2004-12-22 Smithkline Beecham Corp Novel compositions
KR100670798B1 (ko) 2004-12-17 2007-01-17 한국전자통신연구원 데이터베이스 캐시 시스템
DE102005005449A1 (de) 2005-02-04 2006-08-10 Grünenthal GmbH Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
CN101534808A (zh) * 2005-06-27 2009-09-16 拜维尔实验室国际有限公司 丁氨苯丙酮盐的改良释放配制品
AU2006304889A1 (en) * 2005-10-14 2007-04-26 H. Lundbeck A/S Stable pharmaceutical formulations containing escitalopram and bupropion
EP1954257A4 (en) * 2005-10-14 2009-05-20 Lundbeck & Co As H METHOD FOR TREATING DISORDERS OF THE CENTRAL NERVOUS SYSTEM WITH A LOW-DOSED COMBINATION OF ESCITALOPRAM AND BUPROPION
CN101370488B (zh) 2005-11-22 2012-07-18 奥雷西根治疗公司 增加胰岛素敏感性的组合物
DK1954241T3 (da) * 2005-11-28 2012-06-18 Orexigen Therapeutics Inc Zonisamid-formulering med vedvarende frigivelse
AU2007220039A1 (en) * 2006-02-27 2007-09-07 The Board Of Trustees Of The Leland Stanford Junior University Inhibitors of the unfolded protein response and methods for their use
JP2009529051A (ja) 2006-03-07 2009-08-13 オステオスクリーン アイピー， エルエルシー ＨＭＧＣｏ−Ａレダクターゼ阻害剤による骨および軟骨の強化
US8916195B2 (en) 2006-06-05 2014-12-23 Orexigen Therapeutics, Inc. Sustained release formulation of naltrexone
CN101808634A (zh) 2006-06-13 2010-08-18 利兰·斯坦福青年大学托管委员会 半胱氨酸蛋白酶的环氧化物抑制剂
US8703191B2 (en) * 2006-07-25 2014-04-22 Intelgenx Corp. Controlled-release pharmaceutical tablets
US7674479B2 (en) * 2006-07-25 2010-03-09 Intelgenx Corp. Sustained-release bupropion and bupropion/mecamylamine tablets
BRPI0715959A2 (pt) * 2006-08-21 2013-07-30 Jubilant Organosys Ltd composiÇço farmacÊutica de liberaÇço modificada de cloridrato de bupropion
KR20170077291A (ko) 2006-11-09 2017-07-05 오렉시젠 세러퓨틱스 인크. 단위 용량 팩키지
DK2089005T3 (da) 2006-11-09 2010-07-19 Orexigen Therapeutics Inc Lagdelte farmaceutiske formuleringer omfattende et hurtigt opløsende mellemlag
DE102007011485A1 (de) 2007-03-07 2008-09-11 Grünenthal GmbH Darreichungsform mit erschwertem Missbrauch
EP2455076A1 (en) 2007-04-09 2012-05-23 Sepracor Inc. Compositions comprising desvenlafaxine for use in treating sleep-related breathing disorders
EP2167065A1 (en) * 2007-06-18 2010-03-31 The General Hospital Corporation Combination therapy for depression
US20090162434A1 (en) * 2007-12-21 2009-06-25 Disphar International Bv Mesalazine tablet
KR101616246B1 (ko) 2008-01-25 2016-05-02 그뤼넨탈 게엠베하 약제학적 투여형
US9339500B2 (en) 2008-03-04 2016-05-17 Intra-Cellular Therapies, Inc. Methods of treating vasomotor symptoms
AU2009243681B2 (en) 2008-05-09 2013-12-19 Grunenthal Gmbh Process for the preparation of an intermediate powder formulation and a final solid dosage form under usage of a spray congealing step
WO2009158114A1 (en) 2008-05-30 2009-12-30 Orexigen Therapeutics, Inc. Methods for treating visceral fat conditions
TW201039815A (en) 2009-04-13 2010-11-16 Resolvyx Pharmaceuticals Inc Compositions and methods for the treatment of inflammation
TWI473628B (zh) 2009-07-22 2015-02-21 用於對氧化敏感之類鴉片藥劑之抗破壞劑型
WO2011009602A1 (en) 2009-07-22 2011-01-27 Grünenthal GmbH Hot-melt extruded controlled release dosage form
US10610528B2 (en) 2009-12-08 2020-04-07 Intelgenx Corp. Solid oral film dosage forms and methods for making same
US20110136815A1 (en) 2009-12-08 2011-06-09 Horst Zerbe Solid oral film dosage forms and methods for making same
MX344303B (es) 2010-01-11 2016-12-13 Orexigen Therapeutics Inc Metodos para proveer terapia de perdida de peso en pacientes con depresion mayor.
US9579285B2 (en) 2010-02-03 2017-02-28 Gruenenthal Gmbh Preparation of a powdery pharmaceutical composition by means of an extruder
CA2808219C (en) 2010-09-02 2019-05-14 Gruenenthal Gmbh Tamper resistant dosage form comprising inorganic salt
WO2012028318A1 (en) 2010-09-02 2012-03-08 Grünenthal GmbH Tamper resistant dosage form comprising an anionic polymer
EP2627324A4 (en) 2010-10-11 2014-05-07 Univ Leland Stanford Junior SUBSTITUTED BENZAMIDES AND USES THEREOF
DK2632927T3 (en) 2010-10-26 2016-04-11 Mars Inc Boronates AS ARGINSASEINHIBITORER
AU2012289764B2 (en) 2011-07-29 2017-03-02 Grünenthal GmbH Tamper-resistant tablet providing immediate drug release
ES2648129T3 (es) 2011-07-29 2017-12-28 Grünenthal GmbH Pastilla a prueba de manipulación que proporciona una liberación inmediata de un medicamento
ES2761866T3 (es) 2011-11-21 2020-05-21 Calithera Biosciences Inc Inhibidores heterocíclicos de glutaminasa
US20130225697A1 (en) 2012-02-28 2013-08-29 Grunenthal Gmbh Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer
US9296732B2 (en) 2012-04-12 2016-03-29 The Board Of Trustees Of The Leland Stanford Junior University Substituted benzamides and their uses
PL2838512T3 (pl) 2012-04-18 2018-12-31 Grünenthal GmbH Farmaceutyczna postać dawkowania odporna na niewłaściwe użycie i odporna na uderzeniowe uwalnianie dawki
US10064945B2 (en) 2012-05-11 2018-09-04 Gruenenthal Gmbh Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
CN110893181A (zh) 2012-06-06 2020-03-20 纳丙药业有限责任公司 治疗超重和肥胖症的方法
BR112015010955A2 (pt) 2012-11-16 2017-07-11 Calithera Biosciences Inc inibidores de glutaminase heterocíclica
US10100037B2 (en) 2013-03-15 2018-10-16 The Board Of Trustees Of The Leland Stanford Junior University Activity-based probe compounds, compositions, and methods of use
AU2014273227B2 (en) 2013-05-29 2019-08-15 Grunenthal Gmbh Tamper-resistant dosage form containing one or more particles
JP6466417B2 (ja) 2013-05-29 2019-02-06 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング 二峰性放出プロファイルを有する改変防止（ｔａｍｐｅｒ−ｒｅｓｉｓｔａｎｔ）剤形
JP6449871B2 (ja) 2013-07-12 2019-01-09 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング エチレン−酢酸ビニルポリマーを含有する改変防止剤形
EP3073994A1 (en) 2013-11-26 2016-10-05 Grünenthal GmbH Preparation of a powdery pharmaceutical composition by means of cryo-milling
EP3142646A1 (en) 2014-05-12 2017-03-22 Grünenthal GmbH Tamper resistant immediate release capsule formulation comprising tapentadol
EA201692388A1 (ru) 2014-05-26 2017-05-31 Грюненталь Гмбх Лекарственная форма в виде множества частиц, защищенная от вызываемого этанолом сброса дозы
KR20170012562A (ko) 2014-06-13 2017-02-02 칼리테라 바이오사이언시즈 인코포레이티드 글루타미나제 억제제를 사용하는 병용 요법
CA2957225A1 (en) 2014-08-07 2016-02-11 Calithera Biosciences, Inc. Crystal forms of glutaminase inhibitors
JP6663909B2 (ja) 2014-08-13 2020-03-13 エオラス セラピューティクス， インコーポレイテッド オレキシンレセプターモジュレーターとしてのジフルオロピロリジン
US20170333450A1 (en) 2014-10-31 2017-11-23 The Regents Of The University Of California Compositions and methods for treating hiv-associated cognitive dysfunction
NZ734650A (en) 2015-03-10 2023-07-28 Aurigene Oncology Ltd 1,2,4-oxadiazole and thiadiazole compounds as immunomodulators
BR112017021475A2 (pt) 2015-04-24 2018-07-10 Gruenenthal Gmbh forma de dosagem resistente à adulteração (tamper) com liberação imediata e resistência contra extração de solvente
KR20180021117A (ko) 2015-06-23 2018-02-28 칼리테라 바이오사이언시즈, 인코포레이티드 아르기나제 활성 억제를 위한 조성물 및 방법
WO2017003951A1 (en) * 2015-06-29 2017-01-05 Phloronol, Inc. Solid pharmaceutical compositions of brown algae
WO2017042325A1 (en) 2015-09-10 2017-03-16 Grünenthal GmbH Protecting oral overdose with abuse deterrent immediate release formulations
GB2542881B (en) 2015-10-02 2020-01-01 Carr Andrew Crystal forms of ß-nicotinamide mononucleotide
CN108601767A (zh) 2015-10-05 2018-09-28 卡利泰拉生物科技公司 用谷氨酰胺酶抑制剂和免疫肿瘤学药剂的组合疗法
WO2017075363A1 (en) 2015-10-30 2017-05-04 Calithera Biosciences, Inc. Compositions and methods for inhibiting arginase activity
US10745435B2 (en) 2015-11-16 2020-08-18 Cerecor, Inc. Nucleic acid prodrugs
MX2018009656A (es) 2016-02-12 2019-02-20 Astrazeneca Ab Piperidinas halo-sustituidas como moduladores de los receptores de orexinas.
EP3442540A4 (en) 2016-04-14 2019-12-18 Spinnaker Biosciences Inc. POROUS SILICON MATERIALS WITH A METAL SILICATE FOR DELIVERING THERAPEUTIC ACTIVE SUBSTANCES
CA3021677C (en) 2016-04-22 2024-11-12 Viking Therapeutics, Inc. USE OF BETA-AGONISTS OF THYROID HORMONES
US10793590B2 (en) 2016-06-03 2020-10-06 President And Fellows Of Harvard College Antifungal compounds
ES3062420T3 (en) 2016-08-25 2026-04-10 California Inst Of Techn Ascaroside treatment of eosinophilic esophagitis
WO2018039612A1 (en) 2016-08-26 2018-03-01 The Regents Of The University Of California Compositions and methods for promoting hair growth with mpc1 inhibitors
WO2018049014A1 (en) 2016-09-07 2018-03-15 Trustees Of Tufts College Dash inhibitors, and uses related thereto
WO2018049094A1 (en) 2016-09-09 2018-03-15 The Regents Of The University Of California Estrogen receptor ligands, compositions and methods related thereto
TWI767937B (zh) 2016-09-09 2022-06-21 美商卡利泰拉生物科技公司 外核苷酸酶抑制劑及其使用方法
WO2018058029A1 (en) 2016-09-26 2018-03-29 Dana-Farber Cancer Institute, Inc. Chromobox protein inhibitors and uses thereof
US11510931B2 (en) 2016-09-28 2022-11-29 Medicon Pharmaceuticals, Inc. Compositions and methods for treating ophthalmic conditions
HRP20230634T1 (hr) 2016-09-28 2023-10-13 Medicon Pharmaceuticals, Inc. Pripravci za liječenje oftalmoloških stanja
EP3538111B1 (en) 2016-11-08 2022-01-19 Calithera Biosciences, Inc. Arginase inhibitor combination therapies
US11654112B2 (en) 2016-11-22 2023-05-23 Elektrofi, Inc. Particles comprising a therapeutic or diagnostic agent and suspensions and methods of use thereof
SMT202100573T1 (it) 2016-12-22 2021-11-12 Calithera Biosciences Inc Composizioni e metodi per l'inibizione dell'attivita' dell'arginasi
ES2964985T3 (es) 2016-12-23 2024-04-10 Univ Leland Stanford Junior Compuestos sonda basados en actividad, composiciones y métodos de uso
US20200054643A1 (en) 2017-01-18 2020-02-20 Vanderbilt University Fused heterocyclic compounds as selective bmp inhibitors
MA47593A (fr) 2017-02-24 2020-01-01 Merck Patent Gmbh Dérivés de 1, 4, 6-trisubstitué-2-alkyl-1h-benzo[d]imidazole en tant qu'inhibiteurs de dihydroorotate oxygénase
DK3600270T3 (da) 2017-03-31 2023-07-10 Aurigene Oncology Ltd Forbindelser og sammensætninger til behandling af hæmatologiske lidelser
WO2018209288A1 (en) 2017-05-12 2018-11-15 Massachusetts Institute Of Technology Argonaute protein-double stranded rna complexes and uses related thereto
WO2018223032A1 (en) 2017-06-02 2018-12-06 Stealth Biotherapeutics Corp. Crystalline salt forms of sbt-20
KR102642823B1 (ko) 2017-06-30 2024-03-04 더 리전트 오브 더 유니버시티 오브 캘리포니아 모발 성장을 조절하기 위한 조성물 및 방법
WO2019018539A1 (en) 2017-07-19 2019-01-24 California Institute Of Technology PROCESSES FOR PREPARING COMPOUNDS CONTAINING BIS-TETRAHYDROISOQUINOLINE
AU2018306303A1 (en) 2017-07-25 2020-02-20 Elektrofi, Inc. Formation of particles including agents
CN111868039A (zh) 2017-09-26 2020-10-30 加利福尼亚大学董事会 用于治疗癌症的组合物和方法
JP2020536853A (ja) 2017-10-04 2020-12-17 デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド 転写因子ｓａｌｌ４の小分子阻害およびその使用
IL273896B2 (en) 2017-10-11 2025-08-01 Aurigene Oncology Ltd Crystalline forms of 3-substituted 1,2,4-oxadiazole
CA3079628A1 (en) 2017-10-31 2019-05-09 Curis, Inc. Compounds and compositions for treating hematological disorders
AU2018360386B2 (en) 2017-11-03 2023-11-09 Aurigene Oncology Limited Dual inhibitors of TIM-3 and PD-1 pathways
CN111386128A (zh) 2017-11-06 2020-07-07 奥瑞基尼探索技术有限公司 用于免疫调节的联合疗法
CA3085097A1 (en) 2017-12-22 2019-06-27 Medimmune Limited Small molecule modulators of the btb domain of keap1
WO2019152536A1 (en) 2018-01-30 2019-08-08 The Regents Of The University Of California Inhibitors of the wnt/beta-catenin pathway
WO2019175799A2 (en) 2018-03-14 2019-09-19 Aurigene Discovery Technologies Limited Method of modulating tigit and pd-1 signalling pathways using 1,2,4-oxadiazole compounds
WO2019178383A1 (en) 2018-03-14 2019-09-19 Vanderbilt University Inhibition of bmp signaling, compounds, compositions and uses thereof
US10933084B2 (en) 2018-04-12 2021-03-02 MatRx Therapeutics Corporation Compositions and methods for treating elastic fiber breakdown
US11155638B2 (en) 2018-05-08 2021-10-26 Rhode Island Hospital Anti-CHI3L1 antibodies for the detection and/or treatment of nonalcoholic fattly liver disease/nonalcoholic steatonhepatitis and subsequent complications
JP7402225B2 (ja) 2018-05-11 2023-12-20 ロード アイランド ホスピタル ヌクレオシド系逆転写酵素阻害剤を用いて関節障害を処置するための組成物および方法
WO2019226969A1 (en) 2018-05-24 2019-11-28 Elektrofi, Inc. Particles comprising a therapeutic or diagnostic agent and suspensions and methods of use thereof
EP3813841B1 (en) 2018-06-29 2025-08-13 The Regents Of The University Of California New molecular tweezers against neurological disorders and viral infections
BR112021001499A2 (pt) 2018-07-27 2021-04-27 California Institute Of Technology inibidores de cdk e usos dos mesmos
CA3111217A1 (en) 2018-09-05 2020-03-12 The General Hospital Corporation Methods of treating cytokine release syndrome
EP3849310A4 (en) 2018-09-12 2022-07-06 The Board of Regents of the University of Oklahoma COMBINATION CANCER THERAPIES
DK3867223T3 (da) 2018-10-17 2026-03-16 Univ California Prodrugs af alpha-ketoglutarat, alpha-ketobutyrat, alpha-ketoisovalerat og alpha-ketoisohexanoat og anvendelser deraf
JP7504880B2 (ja) 2018-10-26 2024-06-24 ケロス セラピューティクス インコーポレイテッド Ａｌｋ２阻害剤の結晶形
KR20210068591A (ko) 2018-10-31 2021-06-09 주식회사 인투셀 융합된 헤테로시클릭 벤조디아제핀 유도체 및 그의 용도
AU2020209216A1 (en) 2019-01-18 2021-08-26 Astrazeneca Ab PCSK9 inhibitors and methods of use thereof
SG11202107614PA (en) 2019-01-18 2021-08-30 Astrazeneca Ab Pcsk9 inhibitors and methods of use thereof
SG11202107145SA (en) 2019-01-25 2021-08-30 Univ Brown Compositions and methods for treating, preventing or reversing age-associated inflammation and disorders
EP3917500A2 (en) 2019-01-31 2021-12-08 Elektrofi, Inc. Particle formation and morphology
JP2022525157A (ja) 2019-03-14 2022-05-11 アストラゼネカ・アクチエボラーグ 体重減少のためのラナベセスタット
EP3978076A4 (en) 2019-06-03 2023-02-22 Irimajiri Therapeutics Inc. CYCLIC AMIDE COMPOUNDS FOR THE TREATMENT OF RABIES AND METHOD THEREOF
WO2021050953A1 (en) 2019-09-13 2021-03-18 Elektrofi, Inc. Compositions and methods for the delivery of therapeutic biologics for treatment of disease
EP4058434A1 (en) 2019-11-12 2022-09-21 Genzyme Corporation 6-membered heteroarylaminosulfonamides for treating diseases and conditions mediated by deficient cftr activity
WO2021113806A1 (en) 2019-12-05 2021-06-10 Genzyme Corporation Arylamides and methods of use thereof
WO2021113809A1 (en) 2019-12-05 2021-06-10 Genzyme Corporation Arylamides and methods of use thereof
US12545695B2 (en) 2019-12-16 2026-02-10 Unist (Ulsan National Institute Of Science And Technology) Compounds for inhibiting neovascularization factors and use thereof
WO2021142221A1 (en) 2020-01-10 2021-07-15 The Regents Of The University Of California Compositions and methods for the treatment of neurodegenerative diseases
WO2021158959A2 (en) 2020-02-07 2021-08-12 Elektrofi, Inc. Peptide particles and methods of formation
WO2021168271A1 (en) 2020-02-19 2021-08-26 Elektrofi, Inc. Droplet formation and particle morphology
CN115515592A (zh) * 2020-03-05 2022-12-23 艾伯维公司 施用恶拉戈利的方法
WO2021207135A1 (en) 2020-04-06 2021-10-14 The Regents Of The University Of California Compounds and methods for inducing ucp1 expression
JP2023522627A (ja) 2020-04-17 2023-05-31 エレクトロフィ，インコーポレイテッド 連続的な液滴形成及び脱水によって粒子を形成する方法
IL297832A (en) 2020-05-05 2023-01-01 Nuvalent Inc Macrocyclic heteroaromatic chemotherapeutic agents
KR102698413B1 (ko) 2020-05-05 2024-08-26 뉴베일런트, 아이엔씨. 헤테로방향족 거대환식 에터 화학치료제
WO2021263072A1 (en) 2020-06-25 2021-12-30 Dana-Farber Cancer Institute, Inc. Methods of treating disease
CN111830151B (zh) * 2020-07-01 2021-05-04 迪沙药业集团有限公司 盐酸安非他酮组合物质量控制用系统适用性对照品
CA3191163A1 (en) 2020-08-10 2022-02-17 Dana-Farber Cancer Institute, Inc. Fused tricyclic pyrimidine-thieno-pyridine small molecule inhibitors of ubiquitin-specific protease 28
US20230271918A1 (en) 2020-08-10 2023-08-31 Dana-Farber Cancer Institute, Inc. Substituted 3-amino-4-methylbenzenesulfonamides as small molecule inhibitors of ubiquitin-specific protease 28
WO2022035805A1 (en) 2020-08-10 2022-02-17 Dana-Farber Cancer Institute, Inc. Substituted 1,2,4-oxadiazoles as small molecule inhibitors of ubiquitin-specific protease 28
EP4232161A1 (en) 2020-10-23 2023-08-30 Dana-Farber Cancer Institute, Inc. Covalent inhibitors of creatine kinase (ck) and uses thereof for treating and preventing cancer
US20240058344A1 (en) 2020-12-18 2024-02-22 Cornell University Methods of treating neurodegenerative disorders and stat3-linked cancers using suppressors of electron leak
AU2021409394A1 (en) 2020-12-21 2023-07-27 Cornell University Peptide-linked drug delivery system
WO2022150574A1 (en) 2021-01-08 2022-07-14 Cornell University Inhibitors of mycobacterium tuberculosis lipoamide dehydrogenase
EP4323356A1 (en) 2021-04-13 2024-02-21 Nuvalent, Inc. Amino-substituted heterocycles for treating cancers with egfr mutations
MX2024002519A (es) 2021-09-03 2024-05-27 Genzyme Corp Compuestos de indol y metodos de uso.
EP4396176A1 (en) 2021-09-03 2024-07-10 Genzyme Corporation Indole compounds and uses thereof in the treatement of cystic fibrosis
IL311444A (en) 2021-10-01 2024-05-01 Nuvalent Inc Solid forms, pharmaceutical compositions and preparation of heteroaromatic macrocyclic ether compounds
KR20240095536A (ko) 2021-10-01 2024-06-25 뉴베일런트, 아이엔씨. 헤테로방향족 매크로사이클릭 에테르 화합물을 사용한 고형 종양의 치료 방법
WO2023187422A1 (en) 2022-03-31 2023-10-05 Revolo Biotherapeutics Limited Compositions and their use in methods for treating intestinal inflammation
CA3245914A1 (en) 2022-04-07 2023-10-12 Nuvalent, Inc METHODS OF TREATMENT OF A SOLID TUMOR USING (19R)-5-CHLORO-3-ETHYL-16-FLUORO-10,19-DIMETHYL-20-OXA-3,4,10,11,23-PENTAAZAPENTACYCLO[19.3.1.02,6.08,12.013,18]PENTACOSA-1(24),2(6),4,8,11,13,15,17,21(25),22-DECAE-22-AMINE
JP2025512920A (ja) 2022-04-07 2025-04-22 ヌバレント， インク． ヘテロ芳香族大環状エーテル化合物の固体形態、薬学的組成物、及び調製
AU2023260936A1 (en) 2022-04-29 2024-12-05 Halozyme Hypercon, Inc. Injectable suspensions
EP4525906A1 (en) 2022-05-16 2025-03-26 Revolo Biotherapeutics Limited Methods and compositions for preventing or treating food allergies
WO2023250157A1 (en) 2022-06-24 2023-12-28 Cornell University Inhibitors of mycobacterium tuberculosis lipoamide dehydrogenase
CN118785900A (zh) * 2022-06-30 2024-10-15 艾克萨姆治疗公司 包含安非他酮和半胱氨酸的药物组合物
US12156914B2 (en) * 2022-06-30 2024-12-03 Axsome Therapeutics, Inc. Pharmaceutical compositions comprising bupropion and cysteine
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WO2024036097A1 (en) 2022-08-12 2024-02-15 Nuvalent, Inc. Heteroaromatic macrocyclic ether compounds and isotopologues thereof
EP4568969A1 (en) 2022-08-12 2025-06-18 Nuvalent, Inc. Heteroaromatic macrocyclic ether compounds
WO2024073334A1 (en) 2022-09-26 2024-04-04 Rose Research Center, Llc Combination for use in a method of preventing weight gain
WO2024071371A1 (ja) 2022-09-30 2024-04-04 ユビエンス株式会社 複素環式化合物
JPWO2024071370A1 (https=) 2022-09-30 2024-04-04
IL319638A (en) 2022-10-19 2025-05-01 Nuvalent Inc Chemotherapeutic agents of heteroaromatic macrocyclic esters
CN120187444A (zh) 2022-11-04 2025-06-20 第一工业制药株式会社 用于处置或预防神经病理性疼痛和/或炎性疼痛的环状肽衍生物组合物
EP4613282A1 (en) 2022-11-04 2025-09-10 DKS Co. Ltd. Cyclic peptide derivative composition for treating or preventing central nervous system injury/disease
WO2024218571A1 (en) 2023-04-18 2024-10-24 Revolo Biotherapeutics Limited Methods and compositions for preventing or treating eosinophilic esophagitis
WO2024233456A1 (en) 2023-05-05 2024-11-14 The Board Of Regents Of The University Of Oklahoma Variants of adrenomedullin (am) and adrenomedullin 2/intermedin (am2/imd) and methods of use
WO2025037259A1 (en) 2023-08-15 2025-02-20 Revolo Biotherapeutics Limited Methods and compositions for preventing or treating severe asthma
WO2025042868A1 (en) 2023-08-23 2025-02-27 The Board Of Regents Of The University Of Oklahoma Combinations of heteroarotinoids and glycolytic inhibitors for use as cancer treatments
AU2024344058A1 (en) 2023-09-18 2026-04-02 Flagship Pioneering Innovations Vii, Llc Ionizable lipidoid compositions and therapeutic uses thereof
WO2025072117A1 (en) 2023-09-25 2025-04-03 Nuvalent, Inc. Heteroaromatic macrocyclic ether compounds and isotopologues thereof
WO2025072120A1 (en) 2023-09-25 2025-04-03 Nuvalent, Inc. Heteroaromatic macrocyclic ether compounds
WO2025085360A1 (en) 2023-10-16 2025-04-24 The Board Of Regents Of The University Of Oklahoma Heteroarotinoids and/or cdk4/6 inhibitors for treating human papillomavirus (hpv)-induced dysplasias, warts, and cancer in hpv-infected subjects
WO2025088586A1 (en) 2023-10-27 2025-05-01 Brown University Compositions, systems, and methods for treating cancer using tumor treating fields with inhibitors of mif, mica, and/or micb
WO2025106670A1 (en) 2023-11-14 2025-05-22 Flagship Pioneering Innovations Vii, Llc Ionizable lipidoid compositions and therapeutic uses thereof
WO2025212478A1 (en) 2024-04-01 2025-10-09 Nuvalent, Inc. Methods of treating solid tumor using heteroaromatic macrocyclic ether compounds
WO2025235874A1 (en) 2024-05-10 2025-11-13 Schrödinger, Inc. Heterocyclics as egfr inhibitors
WO2025235872A1 (en) 2024-05-10 2025-11-13 Schrödinger, Inc. Heterocyclics as egfr inhibitors
US20250383333A1 (en) 2024-06-12 2025-12-18 Elektrofi, Inc. Determination of particulate contaminants in particles and compositions
WO2026050339A1 (en) 2024-08-27 2026-03-05 Halozyme Hypercon, Inc. Methods of preparing samples for analytical testing

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3819706A (en) * 1969-12-04 1974-06-25 Burroughs Wellcome Co Meta chloro substituted-alpha-butylamino-propiophenones
US3885046A (en) * 1969-12-04 1975-05-20 Burroughs Wellcome Co Meta chloro or fluoro substituted alpha-T-butylaminopropionphenones in the treatment of depression
EP0171457A1 (en) * 1984-08-17 1986-02-19 The Wellcome Foundation Limited Composition for the controlled discharge of an active ingredient, and its preparation
USRE33994E (en) * 1983-08-16 1992-07-14 Burroughs Wellcome Co. Pharmaceutical delivery system
WO1992019226A1 (en) * 1991-05-07 1992-11-12 Dynagen, Inc. A controlled, sustained release delivery system for treating drug dependency

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA948388A (en) * 1970-02-27 1974-06-04 Paul B. Hansen Pattern bonded continuous filament web
US4347257A (en) * 1979-10-09 1982-08-31 Burroughs Wellcome Co. Prolactin suppression in mammals
CH647150A5 (de) * 1980-01-21 1985-01-15 Wellcome Found Zubereitung, enthaltend ein tranquillans und ein propiophenon.
US4347382A (en) * 1980-04-15 1982-08-31 Burroughs Wellcome Co. 3H Labeled compounds
US4355179A (en) * 1980-04-14 1982-10-19 Burroughs Wellcome Co. Radioactive nuclide labeled propiophenone compounds
US4347177A (en) * 1980-04-14 1982-08-31 Burroughs Wellcome Co. Compounds and methods of making them
US4347178A (en) * 1980-04-14 1982-08-31 Burroughs Wellcome Co. Compounds and methods of making
US4356165A (en) * 1980-04-14 1982-10-26 Burroughs Wellcome Co. Bupropion radioimmunoassay, and kit
US4347176A (en) * 1980-04-14 1982-08-31 Burroughs Wellcome Co. Compounds and methods of making same
US4425363A (en) * 1981-05-14 1984-01-10 Burroughs Wellcome Co. Treatment of tardive dyskinesia in mammals
US4435449A (en) * 1981-05-14 1984-03-06 Burroughs Wellcome Co. Treatment of minimal brain dysfunction (MBD)
US4393078A (en) * 1982-03-15 1983-07-12 Burroughs Wellcome Co. Bupropion and ethanol
US4438138A (en) * 1982-12-06 1984-03-20 Burroughs Wellcome Co. Reduction of cholesterol with meta-chloro α-t-butylaminopropiophenone
GB8322007D0 (en) * 1983-08-16 1983-09-21 Wellcome Found Pharmaceutical delivery system
US4507323A (en) * 1984-07-25 1985-03-26 Burroughs Wellcome Co. Treatment of psychosexual dysfunctions
US4769027A (en) * 1984-08-15 1988-09-06 Burroughs Wellcome Co. Delivery system

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3819706A (en) * 1969-12-04 1974-06-25 Burroughs Wellcome Co Meta chloro substituted-alpha-butylamino-propiophenones
US3885046A (en) * 1969-12-04 1975-05-20 Burroughs Wellcome Co Meta chloro or fluoro substituted alpha-T-butylaminopropionphenones in the treatment of depression
USRE33994E (en) * 1983-08-16 1992-07-14 Burroughs Wellcome Co. Pharmaceutical delivery system
EP0171457A1 (en) * 1984-08-17 1986-02-19 The Wellcome Foundation Limited Composition for the controlled discharge of an active ingredient, and its preparation
EP0467488A2 (en) * 1984-08-17 1992-01-22 The Wellcome Foundation Limited Composition for the controlled discharge of an active ingredient
WO1992019226A1 (en) * 1991-05-07 1992-11-12 Dynagen, Inc. A controlled, sustained release delivery system for treating drug dependency

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995003791A1 (en) * 1993-07-30 1995-02-09 The Wellcome Foundation Limited Stabilized pharmaceutical composition containing bupropion
US5541231A (en) * 1993-07-30 1996-07-30 Glaxo Wellcome Inc. Stabilized Pharmaceutical
US5731000A (en) * 1993-07-30 1998-03-24 Glaxo Wellcome Inc. Stabilized pharmaceutical composition containing bupropion
US5763493A (en) * 1993-07-30 1998-06-09 Glaxo Wellcome Inc. Stabilized pharmaceutical
US7098206B2 (en) 1998-01-21 2006-08-29 Smithkline Beecham Corporation Pharmaceutically active morpholinol
US6998400B2 (en) 1998-01-22 2006-02-14 Smithkline Beecham Corporation Pharmaceutically active morpholinol
US6495605B2 (en) 1998-01-29 2002-12-17 Sepracor Inc. Methods and compositions for aiding in smoking cessation and for treating pain and other disorders using optically pure (+)-bupropion
US6110973A (en) * 1998-01-29 2000-08-29 Sepracor Methods for treating obesity and weight gain using optically pure (-)-bupropion
US6277887B1 (en) 1998-01-29 2001-08-21 Sepracor, Inc. Methods for treating Parkinson's disease using optically pure (−)-bupropion
WO1999038499A3 (en) * 1998-01-29 1999-09-30 Sepracor Inc Methods and compositions for aiding in smoking cessation and for treating pain and other disorders using optically pure (-)-bupropion
WO1999038503A1 (en) * 1998-01-29 1999-08-05 Sepracor Inc. Pharmacological uses of optically pure (+)-bupropion
US6369113B2 (en) 1998-01-29 2002-04-09 Sepracor, Inc. Method for treating depression using optically pure (−)-bupropion
US6451860B1 (en) 1998-01-29 2002-09-17 Sepracor, Inc. Methods for treating depression and other disorders using optically pure (−)-bupropion
US6458374B1 (en) 1998-01-29 2002-10-01 Sepracor, Inc. Methods and compositions for treating chronic disorders using optically pure (+)-bupropion
WO1999038504A1 (en) * 1998-01-29 1999-08-05 Sepracor Inc. Pharmaceutical uses of optically pure (-)-bupropion
WO1999038502A1 (en) * 1998-01-29 1999-08-05 Sepracor Inc. Pharmaceutical uses of optically pure (+)-bupropion
US6855820B2 (en) 1999-01-20 2005-02-15 Smithkline Beecham Corporation Pharmaceutically active morpholinol
US6734213B2 (en) 1999-01-20 2004-05-11 Smithkline Beecham Corporation Pharmaceutically active morpholinol
US6337328B1 (en) 1999-03-01 2002-01-08 Sepracor, Inc. Bupropion metabolites and methods of use
US6342496B1 (en) 1999-03-01 2002-01-29 Sepracor Inc. Bupropion metabolites and methods of use
EP1275383A1 (en) * 2001-07-09 2003-01-15 Valpharma S.A. Modified release pharmaceutical composition containing Bupropion HCI as active substance

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AU4725893A (en) 1994-03-15
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IL106693A (en) 1997-06-10
IL106693A0 (en) 1993-12-08
JPH08500110A (ja) 1996-01-09
KR950702827A (ko) 1995-08-23
ATE161422T1 (de) 1998-01-15
CA2142320C (en) 2001-10-09
DE69316015D1 (de) 1998-02-05
CA2142320A1 (en) 1994-03-03
US5427798A (en) 1995-06-27
SG43911A1 (en) 1997-11-14
LU90656I2 (fr) 2001-01-15
HK1004323A1 (en) 1998-11-20
KR100294154B1 (ko) 2001-09-17
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ZA935942B (en) 1995-02-13
EP0656775A1 (en) 1995-06-14
DE69316015T2 (de) 1998-04-16
AU677595B2 (en) 1997-05-01
TW260607B (https=) 1995-10-21
GB9217295D0 (en) 1992-09-30
GR3025794T3 (en) 1998-03-31
EP0656775B1 (en) 1997-12-29

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