IP Library › Granted Patent US 12,264,178
Granted Patent B2
US 12,264,178 · App. 18/910,781 · Granted Apr 1, 2025

Ursolic acid morpholine and diethanolamine salts

Inventor: John J. Talley (St. Louis, MO)
Assignee: EMMYON, INC.
C07J63/008A23L29/03A61K45/06
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,264,178
App. No.
18/910,781
Granted
Apr 1, 2025
Kind
B2
Abstract

The invention provides diethanolamine and morpholine salts of ursolic acid. Compositions containing the salts, and methods of using the salts are also provided.

Claims (53)

1. A method for:

(i) increasing skeletal muscle mass;

(ii) treating skeletal muscle atrophy;

(iii) reducing muscle atrophy;

(iv) treating sarcopenia;

(v) treating cachexia;

(vi) increasing strength;

(vii) treating weakness;

(viii) reducing weakness;

(ix) increasing exercise capacity;

(x) promoting muscle growth;

(xi) increasing the ratio of skeletal muscle to fat;

(xii) reducing fat;

(xiii) treating obesity;

(xiv) treating diabetes;

(xv) lowering blood glucose;

(xvi) treating pre-diabetes;

(xvii) treating metabolic syndrome; or

(xviii) treating insulin resistance;

in a subject in need thereof, the method comprising administering to the subject an effective amount of an ursolic acid salt selected from ursolic acid diethanolamine salt and ursolic acid morpholine salt.

2. The method according to claim 1 , wherein the salt is ursolic acid diethanolamine salt of formula

3. The method according to claim 1 , wherein the salt is ursolic acid morpholine salt of formula

4. The method according to claim 1 , comprising administering to the subject 25 to 1,500 mg of the salt.

5. The method according to claim 4 , wherein the salt is ursolic acid diethanolamine salt of formula

6. The method according to claim 1 , wherein the salt is ursolic acid morpholine salt of formula

7. The method according to claim 1 , wherein the subject is a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, hamster, ferret, fish, bird, or rodent.

8. The method according to claim 7 , wherein the salt is ursolic acid diethanolamine salt of formula

9. The method according to claim 7 , wherein the salt is ursolic acid morpholine salt of formula

10. The method according to claim 1 , comprising administering a composition comprising the salt and a further agent.

11. The method according to claim 10 , wherein the composition comprises 25 to 1,500 mg of the salt.

12. The method according to claim 11 , wherein the salt is ursolic acid diethanolamine salt of formula

13. The method according to claim 11 , wherein the salt is ursolic acid morpholine salt of formula

14. The method according to claim 10 , wherein the composition comprises 50 to 1,000 mg of the salt.

15. The method according to claim 10 , wherein the composition is a pharmaceutical composition, nutraceutical composition, food composition, or dietary supplement.

16. The method according to claim 15 , wherein the salt is ursolic acid morpholine salt of formula

17. The method according to claim 3 , for increasing skeletal muscle mass.

18. The method according to claim 3 , for treating skeletal muscle atrophy.

19. The method according to claim 3 , for treating sarcopenia.

20. The method according to claim 3 , for treating cachexia.

21. The method according to claim 3 , for increasing strength.

22. The method according to claim 3 , for treating weakness.

23. The method according to claim 3 , for increasing exercise capacity.

24. The method according to claim 3 , for promoting muscle growth.

25. The method according to claim 3 , for increasing the ratio of skeletal muscle to fat.

26. The method according to claim 3 , for reducing fat.

27. The method according to claim 3 , for treating obesity.

28. The method according to claim 3 , for treating diabetes.

29. The method according to claim 3 , for lowering blood glucose.

30. The method according to claim 3 , for treating pre-diabetes.

31. The method according to claim 3 , for treating metabolic syndrome.

32. The method according to claim 3 , for treating insulin resistance.

33. The method according to claim 3 , for reducing muscle atrophy.

34. The method according to claim 3 , for reducing weakness.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2024
From: TALLEY, JOHN J.
To: EMMYON, INC.
Reel/Frame 068862/0189 →
Continuity (5)
Division 16811730 · Mar 6, 2020
Continuation In Part PCTUS2018049742 · Sep 6, 2018
Provisional Application 62649938 · Mar 29, 2018
Provisional Application 62558004 · Sep 13, 2017
Related Publication 20250034203A1 · Jan 30, 2025
References Cited (57)
US 9295664B2 · Adams et al. · 2016 [cited by applicant]
US 9856204B2 · Adams et al. · 2018 [cited by applicant]
US 10137136B2 · Adams et al. · 2018 [cited by applicant]
US 20030153538A1 · Kuno et al. · 2003 [cited by applicant]
US 20160304553A1 · Baharaff et al. · 2016 [cited by applicant]
US 20170056414A1 · Slaga et al. · 2017 [cited by applicant]
US 20200207802A1 · Talley · 2020 [cited by applicant]
CN 1450900A · 2003 [cited by applicant]
CN 101891795A · 2010 [cited by applicant]
CN 102241723A · 2011 [cited by applicant]
CN 102516351A · 2012 [cited by applicant]
CN 103037692A · 2013 [cited by applicant]
CN 104688745A · 2015 [cited by applicant]
CN 106822153A · 2017 [cited by applicant]
EP 1321145A1 · 2003 [cited by applicant]
EP 1566170A1 · 2005 [cited by applicant]
JP H1129467A · 1999 [cited by applicant]
JP 2003313774A · 2003 [cited by applicant]
JP 2014507422A · 2014 [cited by applicant]
JP 2015510515A · 2015 [cited by applicant]
JP 2015516422A · 2015 [cited by applicant]
KR 20120028043A · 2012 [cited by applicant]
WO 2002043736A1 · 2002 [cited by applicant]
WO 2002078468A1 · 2002 [cited by applicant]
WO 2011115069A1 · 2011 [cited by applicant]
WO 2011146768A1 · 2011 [cited by applicant]
WO WO2011146768 · 2011 [cited by examiner]
WO 2012170546A1 · 2012 [cited by applicant]
WO 2019055280A1 · 2019 [cited by applicant]
Wozniak, L., Skapska, S., and Marszalek, K. (2015) Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities. [cited by applicant]
Liu, J. (2005) Oleanolic acid and ursolic acid: research perspectives. [cited by applicant]
Sultana, N. (2011) Clinically useful anticancer, antitumor, and antiwrinkle agent, ursolic acid and related derivatives as medicinally important natural product. [cited by applicant]
Liu, J. (1995) Pharmacology of oleanolic acid and ursolic acid. [cited by applicant]
Shanmugam, M. K., Dai, X., Kumar, A. P., Tan, B. K., Sethi, G., and Bishayee, A. (2013) Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. [cited by applicant]
Kashyap, D., Tuli, H. S., and Sharma, A. K. (2016) Ursolic acid (UA): A metabolite with promising therapeutic potential. [cited by applicant]
Lopez-Hortas, L., Perez-Larran, P., Gonzalez-Munoz, M. J., Falque, E., and Dominguez, H. (2018) Recent developments on the extraction and application of ursolic acid. A review. [cited by applicant]
Pironi, A. M., de Araujo, P. R., Fernandes, M. A., Salgado, H. R. N., and Chorilli, M. (2018) Characteristics, Biological Properties and Analytical Methods of Ursolic Acid: A Review. [cited by applicant]
Cargnin, S. T., and Gnoatto, S. B. (2017) Ursolic acid from apple pomace and traditional plants: A valuable triterpenoid with functional properties. [cited by applicant]
Lee, S. U., Park, S. J., Kwak, H. B., Oh, J., Min, Y. K., and Kim, S. H. (2008) Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo. [cited by applicant]
Lu, J., Zheng, Y. L., Wu, D. M., Luo, L., Sun, D. X., and Shan, Q. (2007) Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose. [cited by applicant]
Wang, X. T., Gong, Y., Zhou, B., Yang, J. J., Cheng, Y., Zhao, J. G., and Qi, M. Y. (2018) Ursolic acid ameliorates oxidative stress, inflammation and fibrosis in diabetic cardiomyopathy rats. [cited by applicant]
Zhou, Y., Li, J. S., Zhang, X., Wu, Y. J., Huang, K., and Zheng, L. (2010) Ursolic acid inhibits early lesions of diabetic nephropathy. [cited by applicant]
Ling, C., Jinping, L., Xia, L., and Renyong, Y. (2013) Ursolic Acid provides kidney protection in diabetic rats. [cited by applicant]
Ding, H., Wang, H., Zhu, L., and Wei, W. (2017) Ursolic Acid Ameliorates Early Brain Injury After Experimental Traumatic Brain Injury in Mice by Activating the Nrf2 Pathway. [cited by applicant]
Ma, J. Q., Ding, J., Zhang, L., and Liu, C. M. (2015) Protective effects of ursolic acid in an experimental model of liver fibrosis through Nrf2/ARE pathway. [cited by applicant]
Zhang, T., Su, J., Wang, K., Zhu, T., and Li, X. (2014) Ursolic acid reduces oxidative stress to alleviate early brain injury following experimental subarachnoid hemorrhage. [cited by applicant]
Hwang, T. L., Shen, H. I., Liu, F. C., Tsai, H. I., Wu, Y. C., Chang, F. R., and Yu, H. P. (2014) Ursolic acid inhibits superoxide production in activated neutrophils and attenuates trauma-hemorrhage shock-induced organ… [cited by applicant]
Martinez-Abundis, E., Mendez-Del Villar, M., Perez-Rubio, K. G., Zuniga, L. Y., Cortez-Navarrete, M., Ramirez-Rodriguez, A., and Gonzalez-Ortiz, M. (2016) Novel nutraceutic therapies for the treatment of metabolic syndr… [cited by applicant]
Somova, L. O., Nadar, A., Rammanan, P., and Shode, F. O. (2003) Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension. [cited by applicant]
Somova, L. I., Shode, F. O., Ramnanan, P., and Nadar, A. (2003) Antihypertensive, antiatherosclerotic and antioxidant activity of triterpenoids isolated from [cited by applicant]
Dyle et al., “Systems-based Discovery of Tomatidine as a Natural Small Molecule Inhibitor of Skeletal Muscle Atrophy,” The Journal of Biological Chemistry, vol. 289, No. 21, May 23, 2014, pp. 14913-14924. [cited by applicant]
Kunkel et al., “mRNA Expression Signatures of Human Skeletal Muscle Atrophy Identify a Natural Compound that Increases Muscle Mass,” Cell Metabolism 13, Jun. 8, 2011, pp. 627-638. [cited by applicant]
Kunkel et al., “Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, glucose Intolerance and Fatty Liver Disease,” PLOS One, vol. 7, Issue 6, Jun. 2012 pp. 1-8. [cited by applicant]
International Search Report and Written Opinion of the International Searching Authority from PCT/US2018/049742, mailed Jan. 22, 2019. [cited by applicant]
Qiang LEE et al, A New Brochure of Effective Components in Traditional Chinese Medicine, Peking Union Medical College Press. Jan. 31, 2008. pp. 651-652, Abstract Only. [cited by applicant]
Qingguo Meng et al, “Research Progress in Synthesis and Activity of Ursolic Acid Derivatives”. Journal of Jining Medical College, vol. 40, No. 40: Aug. 20, 2017. pp. 246-247, Abstract Only. [cited by applicant]
Fengjuan Xia et al, “Research progress of structure modification technology in domestic patents related to ursolic acid derivatives”. China Medical Herald, vol. 10, No. 27, Sep. 25, 2013. pp. 33-36, Abstract Only. [cited by applicant]