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Carotenoid compositions and uses thereof

A technology of carotene and composition, applied in the field of delivery and use of pharmaceutical composition, preparation, delivery and use of composition, can solve the problems such as not showing clinical therapeutic effect

Pending Publication Date: 2021-01-15
L E A F HLDG GRP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, none of them have shown clinical therapeutic efficacy

Method used

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  • Carotenoid compositions and uses thereof
  • Carotenoid compositions and uses thereof
  • Carotenoid compositions and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0518] Embodiment 1-trans-production of calcium crocetin liposome

[0519] Trans-crocetin liposomes were produced using two different variants of trans-crocetin, namely: trans-crocetin free acid (TC) and its sodium salt trans-sodium crocetin (STC). Trans-crocetin was encapsulated in liposomes by the following procedure.

[0520] Multiplex bilayer (multilamellar) vesicle (MLV) production :

[0521]First, the lipid components of the liposome lipid membrane are weighed out and combined as a concentrated solution in ethanol at a temperature of about 65°C. In one preparation, the lipids used were hydrogenated soybean phosphatidylcholine, cholesterol, and DSPE-PEG-2000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methyl Oxy(polyethylene glycol)-2000]). The molar ratio of HSPC:cholesterol:PEG-DSPE is about 3:2:0.15. In another preparation, the lipids used were HSPC, cholesterol, PEG-DSPE-2000 and 1-palmitoyl-2-glutaryl-sn-glyceryl-3-phosphocholine (PGPC). The molar rati...

Embodiment 2

[0532] Example 2 - with Preparation of calcium acetate liposomes

[0533] Liposomes loaded with calcium acetate were prepared by the following procedure. First, the lipid components of the liposome lipid membrane are weighed out and combined as a concentrated solution in ethanol at a temperature of about 65°C. In one example, the lipids used were hydrogenated soybean phosphatidylcholine, cholesterol, and DSPE-PEG-2000 (1,2-distearoyl-sn-glyceryl-3-phosphoethanolamine-N-[methoxy -(polyethylene glycol)-2000]).

[0534] The molar ratio of HSPC:cholesterol:PEG-DSPE is about 3:2:0.15. In another example, the lipids used are HSPC, cholesterol, PEG-DSPE-2000, and 1-palmitoyl-2-glutaryl-sn-glyceryl-3-phosphocholine (PGPC). The molar ratio of HSPC:cholesterol:PEG-DSPE:PGPC is about 2.7:2:0.15:0.3.

[0535] Next, calcium acetate was dissolved in aqueous buffer at a concentration of 125 or 250 mM, pH 7.0. The calcium acetate solution was heated to 65°C. The ethanol lipid solution...

Embodiment 3

[0536] Example 3-MTC liposome production and characterization

[0537] Production of trans-crocetin liposomes using a magnesium acetate gradient:

[0538] For the production of trans-magnesium crocetin liposomes, two different molecular variants can be used, namely: trans-crocetin free acid (TC) and its sodium salt, trans-sodium crocetin (STC).

[0539] Liposomes containing magnesium acetate were prepared by the following procedure. First, the lipid components of the liposome membrane are weighed out and combined as a concentrated solution in ethanol at a temperature of about 65°C. In one example, the lipids used were hydrogenated soybean phosphatidylcholine, cholesterol, and DSPE-PEG-2000 (1,2-distearoyl-sn-glyceryl-3-phosphoethanolamine-N-[methoxy -(polyethylene glycol)-2000]). The molar ratio of HSPC:cholesterol:PEG-DSPE is about 3:2:0.15. In another example, the lipids used are HSPC, cholesterol, PEG-DSPE-2000, and 1-palmitoyl-2-glutaryl-sn-glyceryl-3-phosphocholine ...

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Abstract

Provided herein are pharmaceutical compositions comprising carotenoids, including liposomes that encapsulate carotenoids including ionizable carotenoids such as trans-crocetin. The provided compositions have uses in treating diseases, disorders and conditions associated with, but not limited to, infection, endotoxemia, inflammation, sepsis, ischemia, hypoxia, shock, stroke, lung injury, wound healing, traumatic injury, reperfusion injury, cardiovascular disease, kidney disease, liver disease, inflammatory disease, metabolic disease, pulmonary disorders, blood related disorders and hyperproliferative diseases such as cancer. Methods of making, delivering, and using the pharmaceutical compositions are also provided.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application No. 62 / 666,699, filed May 3, 2018, and U.S. Provisional Application No. 62 / 809,123, filed February 22, 2019, each of which is incorporated herein in its entirety. Background technique [0003] Under normal circumstances, bacteria and associated toxins (endotoxemia) should not normally be found in the blood of healthy people. However, it is increasingly recognized that bacteria do enter the blood under certain conditions from sources such as the gut (leaky gut syndrome) or the gingival interface (mainly in patients with poor gum health). The consequence of this process, known as bacterial translocation, is a state of chronic bacteremia (bacteria) in the bloodstream. Bacterial translocation leads to chronic bacteremia, which excretes endotoxins, such as bacterial lipopolysaccharide (LPS), causing chronic low-grade chronic endotoxemia and the resulting chroni...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/01A61K47/22A61K47/24
CPCA61K47/24A61K9/1271A61K9/127A61K9/1278A61K47/10A61K47/32A61K47/34A61K47/26A61K9/0019A61K31/015A61K45/06A61K31/01A61K47/12A61K47/02A61P17/02A61P31/00A61P1/16A61K31/202
Inventor C·尼基萨V·M·莫约耿伯林徐郑虹K·哈利法金光成
Owner L E A F HLDG GRP
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