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KR-102962574-B1 - Carotenoids for the treatment or prevention of nausea

KR102962574B1KR 102962574 B1KR102962574 B1KR 102962574B1KR-102962574-B1

Abstract

The present invention provides a technique relating to nausea and/or vomiting, and in some embodiments, particularly to induced (e.g., chemotherapy-induced) nausea and/or vomiting. Alternatively or additionally, in some embodiments, the invention provides a technique relating to treating or preventing one or more eating disorders (e.g., anorexia nervosa). Furthermore, the invention provides a therapeutic composition for oral delivery comprising a therapeutically effective amount of a C50 carotenoid compound and a pharmaceutically acceptable carrier.

Inventors

  • 루브컨 게리 비.
  • 고빈단 조티 아마라나스
  • 자야마니 엘람파리티

Assignees

  • 더 제너럴 하스피탈 코포레이션

Dates

Publication Date
20260508
Application Date
20190510
Priority Date
20190207

Claims (20)

  1. A composition for treating nausea and/or vomiting in a subject, comprising a therapeutically effective amount of decaprenoxanthin as a C50 carotenoid compound, wherein the subject is diagnosed with cancer and is being treated with chemotherapy or radiation or undergoing surgery, and the nausea and/or vomiting is chemotherapy-induced nausea and vomiting (CINV).
  2. delete
  3. delete
  4. The composition of claim 1 further comprises one or more C50 carotenoid compounds selected from the group consisting of C50-astaxanthin, C50-β-carotene, C50-carotene (16,16-diisopentenylphytoene), C50-zeaxanthin, C50-caloxanthin, C50-nostoxanthin, sarcinaxanthin, sarprenoxanthin, acyclic C50 carotenoid bacterioruberin, C50-canthaxanthin, C50-lycopene, C50-phytoene, and combinations thereof.
  5. delete
  6. In claim 1, the composition is (i) a C50-carotenoid-compound-synthetic microorganism or a component thereof, (ii) a C50-carotenoid-compound-synthetic microorganism extract, (iii) an extracted carotenoid compound, or (iv) a combination thereof or a composition comprising the same.
  7. In claim 6, the above C50-carotenoid-compound-synthetic microorganism is viable or alive in the composition.
  8. In claim 7, the composition is a composition administered in an amount sufficient for the microorganism to colonize the microbiome of the subject.
  9. In claim 6, the composition comprises a culture of the microorganism or is prepared therefrom.
  10. In claim 6, a composition in which the microorganism is a strain found in nature.
  11. In claim 6, a composition in which the microorganism is a manipulated microorganism.
  12. A composition according to claim 11, wherein the engineered microorganism comprises genetic modification and, as a result, produces C50 carotenoid compounds at levels different from those of an unengaged reference microorganism of the same type.
  13. A composition according to claim 1, wherein the composition comprises or delivers a synthesized C50 carotenoid compound.
  14. A composition according to claim 6, wherein the C50-carotenoid-compound-synthesizing microorganism is selected from the group consisting of Cochlea rhizophila, Corynebacterium glutamicum, Athrobacter arylylitetensis, and combinations thereof.
  15. A composition for reducing food aversion in a subject, comprising a therapeutically effective amount of decaprenoxanthin as a C50 carotenoid compound, wherein the subject is diagnosed with cancer and is receiving chemotherapy or radiation treatment or surgery, and the food aversion is induced by chemotherapy.
  16. In claim 15, the composition having a subject having chemotherapy-induced zone and vomiting (CINV) or radiation-induced zone and vomiting (RINV).
  17. In claim 15, the composition having the subject experiencing postoperative nausea and vomiting (PONV).
  18. A composition according to claim 15, wherein the composition further comprises one or more C50 carotenoid compounds selected from the group consisting of C50-astaxanthin, C50-β-carotene, C50-carotene (16,16-diisopentenylphytoene), C50-zeaxanthin, C50-caloxanthin, C50-nostoxanthin, sarcinaxanthin, sarprenoxanthin, acyclic C50 carotenoid bacterioruberin, C50-canthaxanthin, C50-lycopene, C50-phytoene, and combinations thereof.
  19. delete
  20. In claim 1, the composition is (i) a C50-carotenoid-compound-synthetic microorganism or a component thereof, (ii) a C50-carotenoid-compound-synthetic microorganism extract, (iii) an extracted carotenoid compound, or (iv) a combination thereof or a composition comprising the same.

Description

Carotenoids for the treatment or prevention of nausea Claim of priority This application claims the benefit of U.S. Provisional Application No. 62802398 filed on February 7, 2019. The entire contents of said application are incorporated herein by reference. Federally funded research or development This invention was made with government support pursuant to Grant No. AG043184 awarded by the National Institutes of Health. The government holds specific rights to the invention. Chemotherapy-induced nausea and vomiting (CINV) affects 70-80% of patients undergoing chemotherapy and is a major cause of discontinuing cancer treatment. Fig. 1A-Fig. 1E. A) pgp-5p::gfp induction was significantly reduced in eft-3(q145);pgp-5p::gfp animals that ingested the wild type of K. ryzophylla , whereas mutations of K. ryzophylla crtEb(e17) , K. ryzophylla crtI(e10) , and K. ryzophylla crtYe(e2) did not inhibit GFP induction. B) K. rhizophila ingestion significantly reduced pgp-5p::gfp induction in eft-3(q145);pgp-5p::gfp animals, whereas pgp-5p::gfp expression in K. rhizophila mutants was unaffected. Unpaired t-test, **P<0.01. Mean ± sd is indicated. The number of animals analyzed per state is indicated above each bar. ns was not significant compared to eft-3(q145);pgp-5p::gfp ingested with E. coli OP50. C) K. Rhizophila mutant discoloration phenotype. D) Schematic representation of mutations within the carotenoid colony of K. rhizophila . E) Presumed C50 carotenoid biosynthetic pathway in K. rhizophila . Fig. 2A-Fig. 2G A) pgp-5p :: gfp induction was significantly reduced in e ft-3(q145);pgp-5p::gfp animals that ingested the wild type of C. glutamicum , whereas mutations of C. glutamicum ΔcrtEb, ΔcrtI, ΔcrtY , and ΔcrtB did not inhibit GFP induction. B) C. Quantification of pgp-5p::gfp expression in eft-3(q145);pgp-5p::gfp animals ingested with glutamicum wild-type, ΔcrtEb, ΔcrtI, ΔcrtY , and ΔcrtB mutants. Unpaired t-test, ****P<0.0001. Mean ± sd are indicated. The number of animals analyzed per state is indicated above each bar. ns was not significant compared to eft-3(q145);pgp-5p::gfp ingested with E. coli OP50. C) pgp-5p::gfp induction was significantly reduced in eft-3(q145);pgp-5p::gfp animals that ingested wild-type A. arylytensis . D) TLC of K. rhizophila extract exhibiting orange pigment. E) HPLC of K. rhizophila extract showing the absorbance of the orange pigment. The inset shows the elution time and absorbance of various peaks obtained from the extract. F) 750 μg/ml of K. rhizophila extract inhibited eft-3(q145);pgp-5p::gfp in animals. G) Quantification of pgp-5p::gfp expression in eft-3(q145);pgp-5p::gfp animals ingested K. rhizophila wild type, K. rhizophila crtEb(e17), K. rhizophila crtI(e10), and K. rhizophila crtEb(e6) containing control extract or K. rhizophila extract. Figs. 3A-3F A) In response to 10 mg/ml of hygromycin, pgp-5p::gfp induction was significantly reduced in animals fed wild-type K. ryzophylla, whereas mutations in K. ryzophylla crtEb(e17) or K. ryzophylla crtI(e10) did not inhibit GFP induction. B) Animals treated with K. rhizophila carotenoid extracts showed hypersensitivity to hygromycin. Unpaired t-tests compared to wild-type worms that ingested E. coli OP50 containing the solvent extract and hygromycin ****P<0.0001. Mean ± sd are indicated. Data were collected from three independent studies of at least 20 animals per condition. ns was not significant compared to wild-type worms that ingested E. coli OP50 containing the solvent extract without hygromycin. C) Animals treated with K. rhizophila carotenoid extract showed hypersensitivity to emetine. D) Animals treated with K. rhizophila carotenoid extract showed hypersensitivity to cisplatin. E) Animals treated with K. rhizophila carotenoid extract were unable to avoid hygromycin compared to animals treated with the control solvent and hygromycin. F) Animals treated with K. rhizophila carotenoid extract did not avoid cisplatin-comparison animals treated with the control solvent and cisplatin. Unpaired t-test, ****P<0.01, **P<0.0001. Mean ± sd are shown. ns was not significant. Figs. 4A–4E A) pgp-5p::gfp was constitutively induced in animals that ingested E. coli OP50 or K. ryzophylla expressing ZIP-2::mCherry in the intestine under the control of the vha-6 promoter. B) Bile acid supplementation inhibited K. rysophylla -induced pgp-5p::gfp activation deficiency in eft-3(q145);pgp-5p::gfp animals. C) Quantification of K. lysophylla - induced inhibition of pgp-5p::gfp activation deficiency in eft-3(q145);pgp-5p::gfp animals by bile acid as shown in Fig. 4B. Unpaired t-test, ***P<0.0001. Mean ± sd are indicated. The number of animals analyzed per state is indicated above each bar. ns was not significant compared to eft-3(q145);pgp-5p::gfp ingested with E. coli OP50. D) lbp-5 RNAi, chc-1 RNAi, fcho-1 RNAi and dyn-1 RNAi inhibited K. rhizofila- induced pgp-5p::gfp activation deficiency in eft-3(q145);pgp-5p::gfp animals, but rme-1 RNAi or rab-5 RNAi