IP Library › Granted Patent US 12,678,502
Granted Patent B2
US 12,678,502 · App. 17/656,702 · Granted Jul 14, 2026

Compositions having improved bioavailability of therapeutics

Inventors: John Brew (St. Albans, GB); Daniel Gooding (Cambridge, GB); Robin M. Bannister (Saffron Walden, GB)
Assignee: TRx Biosciences Limited
A61K47/14A61K31/12A61K31/192A61K31/196A61K31/216A61K31/4025A61K31/4184A61K31/436A61K31/44A61K31/4418A61K31/4453A61K31/496A61K31/502A61K31/5377A61K31/553A61K31/58A61K31/658A61K31/7135A61K38/12A61K47/28
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Quick Facts
Patent No.
US 12,678,502
App. No.
17/656,702
Filed
Mar 28, 2022
Granted
Jul 14, 2026
Kind
B2
Art Unit
1611
USPC
424/283.1
Abstract

The present specification discloses pharmaceutical composition disclosed herein comprises one or more therapeutic compounds, one or more glycerolipids, and one or more digestion enhancers. The disclosed glycerolipids comprise one or more hard fats and one or more liquid fats. The disclosed digestion enhancers comprise one or more bile acids, one or more phospholipids, one or more free C 14-24 fatty acids, one or more free C 14-24 fatty acid surfactants, or any combination thereof. The present specification also discloses methods and procedures to formulate the disclosed one or more therapeutic compounds into the disclosed pharmaceutical compositions.

Claims (26)

1 . A pharmaceutical composition comprising:

a) one or more pharmaceutically active agents selected from the group consisting of an abiraterone, an amlexanox, an aprepitant, an auranofin, a cannabidiol, a diclofenac, an eliglustat, an ezetimibe, a fenofibrate, an ibuprofen, an icatibant, a mebendazole, a mefenamic acid, a midostaurin, a naproxen, a niflumic acid, a nintedanib, an olaparib, a pirfenidone, a pitolisant, a telmisartan, tetrahydrocannabinol, and combinations thereof; and

b) about 45% to about 95% by weight of the pharmaceutical composition of one or more glycerolipids, the one or more glycerolipids being one or more saturated C 10 -C 22 triglycerides and a mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides; and

c) about 1.0% to about 8.0% by weight of the pharmaceutical composition of one or more free C 14-24 fatty acid surfactants, about 15% to about 40% by weight of the pharmaceutical composition of one or more free C 14-24 fatty acids, or both the one or more free C 14-24 fatty acid surfactants and the one or more free C 14-24 fatty acids; and

wherein the pharmaceutical composition is an anhydrous formulation; and

wherein the pharmaceutical composition is not an emulsion.

2 . The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically active agents are in an amount of about 0.1% to about 25% by weight of the pharmaceutical composition.

3 . The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically active agents are in an amount of about 25 mg/mL to about 600 mg/mL.

4 . The pharmaceutical composition of claim 1 , wherein the one or more glycerolipids are present in an amount of about 45% to about 75% by weight of the pharmaceutical composition.

5 . The pharmaceutical composition of claim 1 , wherein the one or more saturated C 10 -C 22 triglycerides are present in an amount of about 10% to about 35% by weight of the pharmaceutical composition.

6 . The pharmaceutical composition of claim 5 , wherein the one or more saturated C 10 -C 22 triglycerides are a mixture of saturated C 10 -C 18 triglycerides.

7 . The pharmaceutical composition of claim 5 , wherein the one or more saturated C 10 -C 22 triglycerides are present in an amount of about 15% to about 30% by weight of the pharmaceutical composition.

8 . The pharmaceutical composition of claim 5 , wherein the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are present in an amount of about 20% to about 75% by weight of the pharmaceutical composition.

9 . The pharmaceutical composition of claim 8 , wherein the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are a mixture of unsaturated C 16 -C 20 monoglycerides, C 16 -C 20 diglycerides, and C 16 -C 20 triglycerides.

10 . The pharmaceutical composition of claim 8 , wherein the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are present in an amount of about 20% to about 50% by weight of the pharmaceutical composition.

11 . The pharmaceutical composition of claim 8 , wherein the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are present in an amount of about 50% to about 75% by weight of the pharmaceutical composition.

12 . The pharmaceutical composition of claim 5 , wherein the one or more saturated C 10 -C 22 triglycerides and the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are in a triglyceride to mixture weight ratio of about 1:1 to about 1:5.

13 . The pharmaceutical composition of claim 1 , wherein the one or more free C 14-24 fatty acid surfactants are present in an amount of about 2.0% to about 7.0% by weight of the pharmaceutical composition.

14 . The pharmaceutical composition of claim 1 , wherein the one or more free C 14-24 fatty acid surfactants are an oleate alkali metal or alkali earth metal salt, a stearate alkali metal or alkali earth metal salt, a linoleate alkali metal or alkali earth metal salt, or any combination thereof.

15 . The pharmaceutical composition of claim 1 , wherein the one or more free C 14-24 fatty acid surfactants are a sodium oleate, a sodium stearate, a sodium linoleate, or any combination thereof.

16 . The pharmaceutical composition of claim 1 , wherein the one or more free C 14-24 fatty acids are present in an amount of about 20% to about 35% by weight of the pharmaceutical composition.

17 . The pharmaceutical composition of claim 14 , wherein the one or more free C 14-24 fatty acids are an oleic acid, a stearic acid, a linoleic acid, or any combination thereof.

18 . The pharmaceutical composition of claim 1 , wherein the one or more saturated C 10 -C 22 triglycerides are present in an amount of about 10% to about 25% by weight of the pharmaceutical composition, the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are present in an amount of about 50% to about 75% by weight of the pharmaceutical composition, and the one or more free C 14-24 fatty acid surfactants are present in an amount of about 3.0% to about 7.0% by weight of the pharmaceutical composition.

19 . The pharmaceutical composition of claim 1 , wherein the one or more saturated C 10 -C 22 triglycerides are present in an amount of about 15% to about 35% by weight of the pharmaceutical composition, the mixture of unsaturated C 14 -C 22 monoglycerides, unsaturated C 14 -C 22 diglycerides, and unsaturated C 14 -C 22 triglycerides are present in an amount of about 20% to about 45% by weight of the pharmaceutical composition, and the one or more free C 14-24 fatty acids are present in an amount of about 20% to about 35% by weight of the pharmaceutical composition.

20 . The pharmaceutical composition of claim 1 , wherein the one or more glycerolipids are present in an amount of about 70% to about 95% by weight of the pharmaceutical composition.

21 . The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically active agents is an abiraterone, an amlexanox, an aprepitant, an auranofin, a diclofenac, an eliglustat, an ezetimibe, a fenofibrate, an ibuprofen, an icatibant, a mebendazole, a mefenamic acid, a midostaurin, a naproxen, a niflumic acid, a nintedanib, an olaparib, a pirfenidone, a pitolisant, a telmisartan, or a combination thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 14, 2022
From: BANNISTER, ROBIN M; GOODING, DANIEL; BREW, JOHN
To: TRX BIOSCIENCES LIMITED
Reel/Frame 061431/0518 →
Continuity (3)
Provisional Application 63269330 · Mar 14, 2022
Provisional Application 63166995 · Mar 27, 2021
Related Publication 20220305125A1 · Sep 29, 2022
References Cited (66)
US 5082667A · Van · 1992 [cited by applicant]
US 5885486A · Westesen et al. · 1999 [cited by applicant]
US 6063768A · First · 2000 [cited by applicant]
US 6294192B1 · Patel et al. · 2001 [cited by applicant]
US 6451339B2 · Patel et al. · 2002 [cited by applicant]
US 6569463B2 · Patel et al. · 2003 [cited by applicant]
US 6719999B2 · Liu et al. · 2004 [cited by applicant]
US 6720001B2 · Chen et al. · 2004 [cited by applicant]
US 6762203B2 · Koike · 2004 [cited by examiner]
US 6764708B2 · Suzuki · 2004 [cited by examiner]
US 6982281B1 · Chen et al. · 2006 [cited by applicant]
US 7374779B2 · Chen · 2008 [cited by examiner]
US 9339553B2 · Zhang et al. · 2016 [cited by applicant]
US 9861602B2 · Chen et al. · 2018 [cited by applicant]
US 20020028813A1 · Jackson et al. · 2002 [cited by applicant]
US 20060138059A1 · Vair, Jr. et al. · 2006 [cited by applicant]
US 20110092583A1 · Murty · 2011 [cited by examiner]
US 20110195993A1 · Masson et al. · 2011 [cited by applicant]
US 20140357708A1 · Murty · 2014 [cited by examiner]
US 20150150881A1 · Di Paolo et al. · 2015 [cited by applicant]
US 20180251422A1 · Martinez et al. · 2018 [cited by applicant]
US 20200368159A1 · Chen et al. · 2020 [cited by applicant]
US 20210346302A1 · Malhotra et al. · 2021 [cited by applicant]
CN 101366697A · 2009 [cited by examiner]
CN 101507707A · 2009 [cited by applicant]
CN 102813639A · 2012 [cited by applicant]
CN 113546045A · 2021 [cited by applicant]
EP 2220073B1 · 2014 [cited by applicant]
JP 2015508099A · 2015 [cited by applicant]
WO 2005053612A2 · 2005 [cited by applicant]
WO 2006017692A2 · 2006 [cited by applicant]
WO 2010041051A1 · 2010 [cited by applicant]
WO 2010075065A2 · 2010 [cited by applicant]
WO 2012104654A1 · 2012 [cited by applicant]
WO 2012104655A2 · 2012 [cited by applicant]
WO 2013126132A1 · 2013 [cited by applicant]
WO 2014108569A1 · 2014 [cited by applicant]
WO 2014108572A1 · 2014 [cited by applicant]
WO 2014108573A1 · 2014 [cited by applicant]
WO 2014108574A1 · 2014 [cited by applicant]
WO 2014117999A1 · 2014 [cited by applicant]
WO 2017025517A1 · 2017 [cited by applicant]
WO 2020217235A1 · 2020 [cited by applicant]
WO 2022207580A2 · 2022 [cited by applicant]
Voelker, D. R. “Glycerolipid structure, function, and synthesis in eukaryotes.” (2013): 412-418. (Year: 2013). [cited by examiner]
Shi, Feng, et al. “Formulation design, preparation, and in vitro and in vivo characterizations of β-elemene-loaded nanostructured lipid carriers.” International Journal of Nanomedicine (2013): 2533-2541. (Year: 2013). [cited by examiner]
Zhang, Cong, et al. “Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats.” International journal of nan… [cited by examiner]
Moghimipour, Eskandar, Abdulghani Ameri, and Somayeh Handali. “Absorption-enhancing effects of bile salts.” Molecules 20.8 (2015): 14451-14473. (Year: 2015). [cited by examiner]
Kaur, Sarabjot, et al. “Nanostructure lipid carrier (NLC): the new generation of lipid nanoparticles.” Asian Pac J Health Sci 2.2 (2015): 76-93. (Year: 2015). [cited by examiner]
Zhang, Xingwang, et al. “Pharmaceutical dispersion techniques for dissolution and bioavailability enhancement of poorly water-soluble drugs.” Pharmaceutics 10.3 (2018): 74. (Year: 2018). [cited by examiner]
Esmaeli, et al., Preferential PPAR-α Activation Reduces Neuroinflammation, and Blocks Neurodegeneration in vivo, Hum. Mol. Genet. 25(2): 317-327 (2016). [cited by applicant]
Metibemu, et al., Exploring receptor tyrosine kinases-inhibitors in Cancer treatments, Egypt. J. Med. Hum. Genet. 20 (35): 1-16 (2019). [cited by applicant]
Pavlovic, et al., Bile Acids and Their Derivatives as Potential Modifiers of Drug Release and Pharmacokinetic Profiles, Front. Pharmacol. 9(1283): 1-23 (2018). [cited by applicant]
Sarjoj, et al., Current Trends in Lipid Based Delivery Systems and its Application in Drug Delivery, Asian J. Pharm. Clin. Res. 5(3): 4-9 (2012). [cited by applicant]
Shi, et al., Formulation Design, Preparation, and in vitro and in vivo Characterizations of ß-Elemene-Loaded Nanostructured Lipid Carriers, Int. J. Nanomed. 8: 2533-2541 (2013). [cited by applicant]
Tsume, et al., The Biopharmaceutics Classification System: Subclasses for in vivo Predictive Dissolution (IPD) Methodology and IVIVC, Eur. J. Pharm. Sci. 57: 152-163 (2014). [cited by applicant]
Voelker, Glycerolipid Structure, Function, and Synthesis in Eukaryotes, Encyclopedia BioChem. pp. 412-418 (2013). [cited by applicant]
Yousaf, et al., Enhanced Oral Bioavailability of Fenofibrate using Polymeric Nanoparticulated Systems: Physicochemical Characterization and in vivo Investigation, Int. J. Nanomed. 10: 1819-1830 (2015). [cited by applicant]
“Zhang, et al., Nanostructured Lipid Carriers as a Novel Oral Delivery System for Triptolide: Induced Changesin Pharmacokinetics Profile Associated with Reduced Toxicity in Male Rats, Int. J. Nanomed. 9: 1049-1063 (2014… [cited by applicant]
WIPO, PCT Form ISA210, International Search Report for International Patent Application Serial No. PCT/EP2023/056491, pp. 5 (Jun. 15, 2023). [cited by applicant]
WIPO, PCT Form ISA237, Written Opinion for International Patent Application Serial No. PCT/EP2023/056491, pp. 8 (Jun. 15, 2023). [cited by applicant]
WIPO, PCT Form ISA210, International Search Report for International Patent Application Serial No. PCT/EP2023/056506, pp. 12 (Sep. 28, 2023). [cited by applicant]
WIPO, PCT Form ISA237, Written Opinion for International Patent Application Serial No. PCT/EP2023/056506, pp. 25 (Sep. 28, 2023). [cited by applicant]
WIPO, PCT Form IB373, International Preliminary Report on Patentability for International Patent Application Serial No. PCT/EP2022/058180, pp. 9 (Oct. 3, 2023). [cited by applicant]
WIPO, PCT Form ISA210, International Search Report for International Patent Application Serial No. PCT/EP2022/058180, pp. 5 (Nov. 17, 2022). [cited by applicant]
WIPO, PCT ISA 237, Written Opinion for International Patent Application Serial No. PCT/EP2022/058180, pp. 11 (Nov. 17, 2022). [cited by applicant]