Fibrate Compositions for Treating Inflammation and Neuroinflammation - Patent application

Abstract

The present disclosure discloses a pharmaceutical composition comprising one or more fibrates, one or more glycerolipids, and one or more digestive enhancers. The disclosed glycerolipids include one or more hard fats and one or more liquid fats. The disclosed digestive enhancers include one or more bile acids, one or more phospholipids, one or more free C 14-24 Fatty acids, with at least one free C 14-24 The present specification also discloses the method and procedure of formulating one or more of the disclosed fibrates into the disclosed pharmaceutical composition.The present specification further discloses the method and use of the disclosed pharmaceutical composition in treating inflammation and / or neuroinflammation.

Description

[Technical Field]

[0001] This application is an international patent application claiming the benefit of priority and entitled to the filing dates of U.S. Provisional Patent Application No. 63 / 362,005, filed March 28, 2022, and U.S. Provisional Patent Application No. 63 / 269,327, filed March 14, 2022, the contents of each of which are incorporated herein by reference in their entirety. [Background technology]

[0002] Inflammation involves the activation of the immune system in response to harmful stimuli, such as pathogens, infections, irritants, or cellular damage. As a stereotypical response, inflammation is a mechanism of innate immunity, as opposed to adaptive immunity, which is specific to each pathogen. Inflammation can be classified as either acute or chronic. Generally speaking, acute inflammation is mediated by granulocytes, while chronic inflammation is mediated by mononuclear cells, such as monocytes and lymphocytes.

[0003] Acute inflammation is the body's initial defense response to remove harmful stimuli by maintaining tissue integrity and contributing to tissue repair. It is part of the body's natural defense system against injury and disease. Without acute inflammation, wounds and infections would never heal, and the progressive destruction of tissue would impair the survival of the organism.

[0004] The process of acute inflammation is initiated by cells already present in all tissues, primarily resident macrophages, dendritic cells, histiocytes, Kupffer cells, mast cells, vascular endothelial cells, and vascular smooth muscle cells. Upon initiation of a noxious stimulus, these cells undergo activation and release inflammatory mediators and sensitizing molecules, such as proinflammatory cytokines, proinflammatory prostaglandins, leukotrienes, histamine, serotonin, neutral proteases, bradykinin, and nitric oxide. These inflammatory molecules regulate a complex series of biological events involving the local vasculature, immune system, and cellular and acellular components at the site of injured tissue to propagate and mature the inflammatory response. These events typically result in the induction of an acute inflammatory response characterized by: 1) increased blood flow into tissues, thereby causing erythema (redness and warmth), which may spread beyond the site (a flare reaction); 2) increased vascular permeability, which increases plasma leakage into tissues, thereby causing edema (swelling); 3) altered excitability of specific sensory neurons, resulting in hypersensitivity and pain; 4) stimulated release of proinflammatory molecules from peripheral nerve endings, such as neuropeptides (e.g., substance P and calcitonin gene-related peptide (CGRP)), prostaglandins, and amino acids (e.g., glutamate); and 5) increased migration of leukocytes, primarily granulocytes, from blood vessels into tissues. The acute inflammatory response requires a constant stimulus to persist and must be actively terminated when no longer needed. Thus, acute inflammation ceases when the noxious stimulus is removed.

[0005] However, severe or prolonged harmful stimuli result in a chronic inflammatory response, which leads to a progressive shift in the types of cells present at the site of tissue damage. Chronic inflammation can be characterized as the simultaneous destruction and healing of tissue from the inflammatory process, ultimately resulting in injury rather than mediating repair. Therefore, chronic inflammation is a disease. Because inflammatory responses can occur anywhere in the body, chronic inflammation is implicated in the pathophysiology of a wide range of seemingly unrelated disorders that underlie a large and diverse group of human diseases. For example, chronic inflammation is involved in a variety of diseases, including cardiovascular disease, cancer, allergies, obesity, diabetes, digestive disorders, degenerative diseases, autoimmune disorders, and Alzheimer's disease.

[0006] Attempts to treat chronic inflammation have met with limited success. This is due, in part, to the fact that the pathogenesis of chronic inflammation is a complex response based in part on a variety of proinflammatory molecules and numerous inflammation-mediating and sensitizing molecules that appear to induce inflammation through redundant mechanisms. Furthermore, in addition to blocking proinflammatory molecules, many anti-inflammatory drugs also inhibit regulatory loops that release endogenous anti-inflammatory molecules. For example, NSAIDs reduce inflammation by blocking the enzymatic activity of cyclooxygenase, a key enzyme that catalyzes the conversion of arachidonic acid to prostaglandins and leukotrienes. Thus, NSAIDs reduce inflammation by preventing the synthesis of all prostaglandins. However, NSAIDs not only prevent the synthesis of proinflammatory prostaglandins, but also prevent the synthesis of anti-inflammatory prostaglandins. Therefore, NSAIDs have met with limited success because they block endogenous anti-inflammatory responses, which may in some cases prolong chronic inflammation. Therefore, compounds, compositions, uses, and methods that preferentially inhibit proinflammatory responses would be highly desirable for treating chronic inflammation.

[0007] Neuroinflammation is an inflammatory response of nervous tissue that can be both acute and chronic. The acute neuroinflammatory response is a well-established defense against harmful conditions such as infections, toxins, and neuronal injury. Regarding the peripheral nervous system (PNS), the neuroinflammatory response is managed in a similar manner to the inflammatory response. Because the blood-brain barrier (BBB) ​​typically prevents peripheral immune cells from entering the CNS, the central nervous system (CNS) is considered an immunologically privileged site. Instead, in response to inflammatory triggers, resident glial cells called microglia are activated to destroy infectious agents before they damage nervous tissue, thus representing the primary form of active immune defense in the CNS. However, when the balance between anti-inflammatory and pro-inflammatory signaling is disrupted, microglia become chronically activated, leading to the overproduction of pro-inflammatory factors (i.e., cytokines) and the progression of neurodegenerative changes (e.g., neuronal atrophy and loss of function). Activation of chronic neuroinflammation further induces the infiltration of immune cells from the periphery across the BBB, promoting neuroinflammatory and neurodegenerative processes. Much research has focused on the central role of neuroinflammation in the pathogenesis of many conditions related to the CNS, including traumatic brain injury, stroke, Alzheimer's disease, postoperative cognitive decline / perioperative neurocognitive impairment, and now even long-term cognitive side effects from SARS-CoV-2. However, attempts to treat neuroinflammation have met with limited success, primarily because NSAIDs are typically formulated for minimal blood-brain barrier penetration. Therefore, compounds, compositions, uses, and methods that can successfully deliver anti-inflammatory agents to the brain would be highly desirable for treating neuroinflammation.

[0008] The present specification provides an alternative approach in which the pharmaceutical compositions disclosed herein are formulated to rely on the physiological lipid digestion and absorption system to achieve absorption and enhanced efficacy, increasing the bioavailability of one or more fibrates to better facilitate the treatment of both inflammation and neuroinflammation. Summary of the Invention

[0009] Embodiments of the present specification partially disclose a pharmaceutical composition for use in treating inflammation, comprising: a) one or more fibrates; b) one or more glycerolipids; and c) one or more digestive enhancers. The fibrates disclosed herein can be bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, and / or simfibrate. The glycerolipids disclosed herein include hard fats and liquid fats. Hard fats are glycerolipids that are solid at 18°C ​​and contain triglycerides. Liquid fats are glycerolipids that are liquid at 18°C ​​and also include partially hydrolyzed glycerolipids and monoglycerides. The digestive enhancers disclosed herein include one or more bile acids, one or more phospholipids, one or more free C 14-24 The compositions disclosed herein may further comprise one or more pharmaceutically acceptable stabilizers, including fatty acid surfactants, one or more fatty acid salts, one or more fatty acid derivatives with polyhydroxylated head groups, one or more steroid surfactants, or any combination thereof.

[0010] Another aspect of the present disclosure partially discloses a pharmaceutical composition for use in treating neuroinflammation, comprising: a) one or more fibrates; b) one or more glycerolipids; and c) one or more digestive enhancers. The fibrates disclosed herein can be bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, and / or simfibrate. The glycerolipids disclosed herein include hard fats and liquid fats. Hard fats are glycerolipids that are solid at 18°C ​​and contain triglycerides. Liquid fats are glycerolipids that are liquid at 18°C ​​and also include partially hydrolyzed glycerolipids and monoglycerides. The digestive enhancers disclosed herein include one or more bile acids, one or more phospholipids, one or more free C 14-24The compositions disclosed herein may further comprise one or more pharmaceutically acceptable stabilizers, including fatty acid surfactants, one or more fatty acid salts, one or more fatty acid derivatives with polyhydroxylated head groups, one or more steroid surfactants, or any combination thereof.

[0011] Another aspect herein discloses a method of treating an individual having inflammation, comprising administering to an individual in need thereof a composition disclosed herein, wherein administration reduces symptoms associated with the inflammation, thereby treating the individual.

[0012] Another aspect herein discloses a method of treating an individual having neuroinflammation, comprising administering to an individual in need thereof a composition disclosed herein, whereby the administration reduces symptoms associated with neuroinflammation, thereby treating the individual.

[0013] Another aspect of the present specification discloses the use of the compositions disclosed herein in the manufacture of a medicament for treating inflammation.

[0014] Another aspect of the present specification discloses the use of the compositions disclosed herein in the manufacture of a medicament for treating neuroinflammation.

[0015] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate aspects of the disclosed subject matter in at least one of its exemplary embodiments, as defined in more detail in the following description. Features, elements, and aspects of the disclosure are referenced by numerals, with like numerals in different drawings representing the same, equivalent, or similar features, elements, or aspects according to one or more embodiments. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating principles described herein and provided by exemplary embodiments of the invention. In such drawings, [Brief explanation of the drawings]

[0016] [Figure 1A]1A shows a representative PXRD spectrum analyzing the disclosed pharmaceutical compositions containing fenofibrate. FIG. 1B shows a representative PXRD spectrum of GELCURE® 43 / 01 standard. [Figure 1B] 1A and 1B show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate and cholic acid standard, respectively. [Figure 1C] 1A and 1B show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate and a representative PXRD spectrum of a fenofibrate standard. [Figure 1D] 1A-1D show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate and vehicle standards. [Figure 1E] 1E shows a representative PXRD spectrum analyzing a disclosed pharmaceutical composition containing fenofibrate.FIG. 1F shows a representative PXRD spectrum analyzing a disclosed pharmaceutical composition containing a fenofibrate standard.FIG. [Figure 1F] 1F shows a representative PXRD spectrum analyzing a disclosed pharmaceutical composition comprising fenofibrate. The figure shows a representative PXRD spectrum of a fenofibrate standard overlaid on a representative PXRD spectrum of a disclosed pharmaceutical composition comprising a fenofibrate standard, with asterisks above peaks indicating overlap of associated peaks. [Figure 1G] 1G shows a representative PXRD spectrum analyzing the disclosed pharmaceutical compositions containing fenofibrate. The figure shows a representative PXRD spectrum of a cholic acid standard overlaid on a representative PXRD spectrum of a vehicle standard, with asterisks above peaks indicating overlap of the associated peaks. [Figure 1H]1H shows a representative PXRD spectrum analyzing the disclosed pharmaceutical compositions containing fenofibrate. Figure 1H shows a representative PXRD spectrum of a cholic acid standard overlaid on a disclosed pharmaceutical composition containing a fenofibrate standard, where asterisks above peaks indicate overlap of the relevant peaks.

[0017] [Figure 2A] 2A shows a representative UHPLC tracing of fenofibric acid levels in blood after oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing fenofibrate. [Figure 2B] 2B shows a representative UHPLC tracing of fenofibric acid levels in the brain after oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing fenofibrate.

[0018] [Figure 3A] 3A shows a representative UHPLC tracing of fenofibric acid levels in blood after oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing fenofibrate. [Figure 3B] 3B shows a representative UHPLC tracing of fenofibric acid levels in the brain after oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing fenofibrate.

[0019] [Figure 4] FIG. 4 shows representative UHPLC tracings of fenofibric acid levels in blood following oral administration of 3 mg / kg, 10 mg / kg, 30 mg / kg, and 100 mg / kg of the disclosed pharmaceutical compositions containing fenofibrate.

[0020] [Figure 5A]Figure 5A shows bar graphs of blood cytokine levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 of LPS challenge. IL-1β levels are shown. (Bars represent SEM. ***=p<0.001 vs. vehicle control.) [Figure 5B] Figure 5B shows bar graphs of blood cytokine levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 of LPS challenge. IL-6 levels are shown. (Bars represent SEM. **=p<0.01, ***=p<0.001 vs. vehicle control.) [Figure 5C] Figure 5C shows bar graphs of blood cytokine levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 of LPS challenge. TNFα levels are shown. (Bars represent SEM. *=p<0.05, **=p<0.01, ***=p<0.001 vs. vehicle control.) [Figure 5D] Figure 5D shows bar graphs of blood cytokine levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 of LPS challenge. MCP-1 levels are shown. (Bars represent SEM. ***=p<0.001 vs. vehicle control.) [Figure 5E] Figure 5E shows bar graphs of blood cytokine levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 of LPS challenge. IL-10 levels are shown. (Bars represent SEM. **=p<0.01, ***=p<0.001 vs. vehicle control.) [Figure 5F] Figure 5F shows bar graphs of blood cytokine levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 of LPS challenge. MCP-2 levels are shown. (Bars represent SEM. ***=p<0.001 vs. vehicle control.)

[0021] [Figure 6A]Figure 6A shows bar graphs of blood cytokine levels in animals that received 5 days of pretreatment before 5 days of LPS challenge. IL-1β levels are shown. (Bars represent SEM. **=p<0.01, ***=p<0.001) [Figure 6B] Figure 6B shows bar graphs of blood cytokine levels in animals receiving 5 days of pretreatment prior to 5 days of LPS challenge. IL-6 levels are shown. (Bars represent SEM. ***=p<0.001) [Figure 6C] Figure 6C shows bar graphs of blood cytokine levels and TNFα levels in animals that received 5 days of pretreatment before 5 days of LPS challenge. (Bars represent SEM. *=p<0.05, ***=p<0.001) [Figure 6D] Figure 6D shows bar graphs of blood cytokine levels and MCP-1 levels in animals that received 5 days of pretreatment before 5 days of LPS challenge. (Bars represent SEM. ***=p<0.001) [Figure 6E] Figure 6E shows bar graphs of blood cytokine levels in animals receiving 5 days of pretreatment prior to 5 days of LPS challenge. IL-10 levels are shown. (Bars represent SEM. ***=p<0.001) [Figure 6F] Figure 6F shows bar graphs of blood cytokine levels and MCP-2 levels in animals that received 5 days of pretreatment before 5 days of LPS challenge. (Bars represent SEM. ***=p<0.001)

[0022] [Figure 7A] Figure 7A shows bar graphs of brain cytokine levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 prior to the first LPS challenge. IL-1β levels are shown. (Bars represent SEM. **=p<0.01, ***=p<0.001 vs. vehicle control.) [Figure 7B]Figure 7B shows bar graphs of brain cytokine levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 prior to the first LPS challenge. IL-6 levels are shown. (Bars represent SEM. *=p<0.05, ***=p<0.001 vs. vehicle control.) [Figure 7C] Figure 7C shows bar graphs of brain cytokine levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 prior to the first LPS challenge. TNFα levels. (Bars represent SEM. *=p<0.05, ***=p<0.001 vs. vehicle control.) [Figure 7D] Figure 7D shows bar graphs of brain cytokine levels and MCP-1 levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 prior to the first LPS challenge. (Bars represent SEM. ***=p<0.001 vs. vehicle control.) [Figure 7E] Figure 7E shows bar graphs of brain cytokine levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 prior to the first LPS challenge. IL-10 levels are shown. (Bars represent SEM. *=p<0.05 vs. vehicle control.) [Figure 7F] Figure 7F shows bar graphs of brain cytokine levels and MCP-2 levels in animals subjected to 5 days of LPS challenge with treatment administered only on day 1 prior to the first LPS challenge. (Bars represent SEM. ***=p<0.001 vs. vehicle control.)

[0023] [Figure 8A] Figure 8A shows bar graphs of brain cytokine levels in animals receiving 5 days of pretreatment prior to 5 days of LPS challenge. IL-1β levels are shown. (Bars represent SEM. ***=p<0.001 vs. vehicle control) [Figure 8B]Figure 8B shows bar graphs of brain cytokine levels and IL-6 levels in animals that received 5 days of pretreatment before 5 days of LPS challenge. (Bars show SEM. **=p<0.01, ***=p<0.001 vs. vehicle control) [Figure 8C] Figure 8C shows bar graphs of brain cytokine levels and TNFα levels in animals that received 5 days of pretreatment before 5 days of LPS challenge. (Bars show SEM. **=p<0.01, ***=p<0.001 vs. vehicle control) [Figure 8D] Figure 8D shows bar graphs of brain cytokine levels and MCP-1 levels in animals that received 5 days of pretreatment before 5 days of LPS challenge. (Bars show SEM. *=p<0.05, ***=p<0.001 vs. vehicle control) [Figure 8E] Figure 8E shows bar graphs of brain cytokine levels and IL-10 levels in animals that received 5 days of pretreatment prior to 5 days of LPS challenge. (Bars represent SEM. *=p<0.05 vs. vehicle control.) [Figure 8F] Figure 8F shows bar graphs of brain cytokine levels and MCP-2 levels in animals that received 5 days of pretreatment before 5 days of LPS challenge. (Bars show SEM. ***=p<0.001 vs. vehicle control)

[0024] [Figure 9A] Figure 9A shows a bar graph depicting the percentage level of IBA-1+ cells per high-power field (HPF, ×400) in hippocampal sections of the brain. The figure shows the percentage level of cells present in hippocampal sections stained with anti-IBA-1 antibody. (Bars represent SEM. *=p<0.05, ***=p<0.001 vs. vehicle control, #=p<0.05 vs. CMF2.) [Figure 9B]Figure 9B shows a bar graph depicting the percentage levels of CD-68+ cells per high-power field (HPF, ×400) in hippocampal sections of the brain. The figure shows the percentage levels of cells present in hippocampal sections stained with anti-CD-68 antibody. (Bars represent SEM. *=p<0.05, **=p<0.01, ***=p<0.001 vs. vehicle control; #=p<0.05, ##=p<0.01 vs. CMF2). [Figure 9C] Figure 9C shows a bar graph depicting the percentage levels of IBA-1+ cells per high-power field (HPF, ×400) in brain cortical sections. The figure shows the percentage levels of cells present in cortical sections stained with anti-IBA-1 antibody. (Bars represent SEM. *=p<0.05, **=p<0.01, ***=p<0.001 vs. vehicle control; #=p<0.05, ##=p<0.01 vs. CMF2.) [Figure 9D] Figure 9D shows a bar graph depicting the percentage levels of CD-68+ cells per high-power field (HPF, ×400) in brain cortical sections. The figure shows the percentage levels of cells present in cortical sections stained with anti-CD-68 antibody. (Bars represent SEM. *=p<0.05, **=p<0.01, ***=p<0.001 vs. vehicle control; ###=p<0.001 vs. CMF2.)

[0025] [Figure 10] FIG. 10 is a bar graph showing fenofibric acid levels in cerebrospinal fluid (CSF) after oral administration of 70 mg, 140 mg, and 125 mg of the disclosed pharmaceutical compositions containing fenofibrate (bars represent minimum and maximum concentrations measured; *=mean; boxes represent Q1 (upper box) and Q3 (lower box); line separating the Q1 and Q3 boxes represents median). DETAILED DESCRIPTION OF THE INVENTION

[0026] Fibrates are a class of fibric acid derivatives and amphipathic carboxylic acids. Fibrates activate peroxisome proliferator-activated receptors (PPARs), particularly PPARα. PPARs are a class of ligand-activated nuclear receptors that regulate carbohydrate (or glucose) and fat metabolism, adipose tissue differentiation, endothelial function, and inflammation. PPAR antagonism mediates lipid-level-modifying properties, such as lowering triglycerides and LDL, and increasing HDL levels by increasing lipolysis, activating lipoprotein lipase, and reducing apoprotein C-III. Therefore, fibrates are considered hypolipidemic agents and have been used to treat various metabolic disorders, primarily hypercholesterolemia (high cholesterol). PPAR agonism also results in a phenotypic shift from an M1 / TH1 pro-inflammatory to an M2 / TH2 anti-inflammatory phenotype, and PPAR receptor agonism acts in a complementary manner to COX inhibition, allowing for complete resolution of inflammation.

[0027] Fenofibrate is an example of a fibrate. This compound is a fibric acid derivative containing fenofibric acid linked to an isopropyl ester. In vivo, the isopropyl ester of fenofibrate is completely hydrolyzed by hepatic carboxylesterase 1 to produce fenofibric acid. Therefore, fenofibrate can be considered a prodrug of fenofibric acid. Interestingly, both fenofibrate and fenofibric acid exhibit complimentary pharmacological properties that enable complete resolution of inflammation. For example, the primary anti-inflammatory effect of fenofibric acid involves its PPARα agonist activity, which is mediated through multiple mechanisms. On the other hand, fenofibrate mediates most of its anti-inflammatory activity through selective inhibition of cyclooxygenase 2 (COX2) activity and agonism of cannabinoid receptor type 2 (CB2).

[0028] Therefore, one advantage of utilizing the combined activity of fenofibrate and fenofibric acid to treat inflammation is their ability to affect three independent signaling pathways that mediate the inflammatory response. Furthermore, unlike traditional NSAIDs and selective COX2 inhibitors, fenofibrate and fenofibric acid do not have the potential for gastric erosion or cardiac burden. Therefore, the ability to fully resolve inflammation by utilizing the activity of fenofibrate and fenofibric acid would be highly beneficial.

[0029] One obstacle to utilizing these three complimentary pharmacological agents in resolving inflammation is the rate at which fenofibrate is converted to fenofibric acid. Its rapid hydrolysis significantly limits the therapeutic effects that this compound can exert. Therefore, a formulation that can slow but not prevent its conversion to fenofibric acid would be advantageous for inducing the anti-inflammatory effects mediated by PPARα and CB2 activation and COX2 inhibition. The disclosed pharmaceutical composition achieves such a delay in the hydrolysis of fenofibrate to fenofibric acid. Furthermore, to enhance the therapeutic effects of fenofibrate in the blood, the disclosed pharmaceutical composition surprisingly enables the delivery of both fenofibrate and fenofibric acid to the brain, thereby enabling these fibrates to treat neuroinflammation.

[0030] The majority of digestion of dietary organic macromolecules and the absorption of almost all of the resulting breakdown products occur in the small intestine. The luminal wall of the small intestine is lined with numerous protrusions called villi, each of which contains enterocytes called absorptive epithelial cells. Absorptive epithelial cells not only secrete enzymes that digest proteins (polypeptides), carbohydrates (polysaccharides), and fats (lipids), but also absorb amino acid, monosaccharide, and fatty acid breakdown products. Interestingly, however, absorptive epithelial cells process these breakdown products differently: amino acids and monosaccharides are taken up by capillaries and transported throughout the body via the blood system, while fatty acids are taken up by blind-ended lymphatic vessels called lacteals and then transported throughout the body via the lymphatic system. The disclosed pharmaceutical composition takes advantage of this differential processing by formulating fibrates, which are preferentially processed by absorptive epithelial cells, in a manner that allows these compounds to be taken up and transported through the lymphatic system.

[0031] Dietary lipids typically consumed by mammals comprise 90% triglycerides and small amounts of cholesterol esters and phospholipids. Unlike proteins and carbohydrates, dietary lipids are hydrophobic molecules that cannot dissolve in the fluid present in the lumen of the small intestine and instead aggregate together to form fat globules. Pancreatic lipase is a water-soluble enzyme that cleaves ester bonds and breaks down lipid triglycerides into fatty acids and glycerol. However, due to its hydrophilicity, lipase remains in the intestinal fluid and cannot dissolve in fat globules; therefore, it can only access and cleave triglycerides located at the surface where the fat globules come into contact with the intestinal fluid. To increase the efficiency and cleavage rate at which lipase can break down lipids in the small intestine, the liver produces a fluid called bile. Bile contains amphipathic molecules, such as bile salts including sodium cholate and sodium chenodeoxycholate, phospholipids including lecithin, and the hydrophobic steroid cholesterol. When bile enters the small intestine, it mixes with the fat globules in such a way that bile salts and phospholipids intercalate with these structures, breaking them down into smaller units called emulsion droplets, while also recruiting amphiphilic molecules called coliapses. Colipase is a protein coenzyme that binds lipase to emulsion droplets and stabilizes the enzyme in its active conformation. Thus, emulsification greatly increases the surface area over which lipase can act on triglycerides, increasing its efficiency and catalytic rate, thereby enabling sufficient lipid digestion in the small intestine.

[0032] As lipid triglyceride digestion progresses, the resulting free fatty acids, which are hydrophobic and insoluble in intestinal fluids, associate with bile-derived phospholipids to form small droplets called mixed micelles, which are composed of phospholipids and bile salts that encapsulate the free fatty acids. These mixed micelles, which are approximately 200–500 times smaller than emulsion droplets, fuse with the membranes of absorptive epithelial cells, allowing the free fatty acids to enter the cytosol of these cells. Once inside the absorptive epithelial cells, the free fatty acids are transported into the lumen of the smooth endoplasmic reticulum, where they are converted back to triglycerides and assemble with cholesterol and phospholipids into spherical lipid structures. These lipid structures are transported to the rough endoplasmic reticulum, where the apoprotein ApoB-48 binds to the surface to form large lipoproteins called chylomicrons. The chylomicrons are then packaged in the Golgi apparatus and exported to the basolateral side of the absorptive epithelial cells via exocytosis. Because chylomicrons are too large to be taken up by capillaries, these lipoproteins enter the lymphatic system via lacteals in a process dependent on ApoB-48. They then circulate through lymphatic vessels and are excreted into the blood via the thoracic duct, bypassing the hepatic circulation. Once in the blood, these lipoproteins migrate to various extrahepatic tissues, where their triglycerides are hydrolyzed by the activity of lipoprotein lipase, allowing the released free fatty acids and glycerol to be absorbed by the tissues. Once most of the triglycerides are hydrolyzed, chylomicron remnants are formed and taken up by the liver, thereby transporting dietary fat to this organ as well.

[0033] The present specification discloses a pharmaceutical composition that is formulated for oral delivery, so that the fibrates present in the pharmaceutical composition are preferentially absorbed into lymphatic system.The pharmaceutical composition disclosed herein comprises one or more fibrates, one or more glycerolipids, and one or more digestive enhancers.The digestive enhancers disclosed herein, together with glycerolipids, increase the solubility of one or more fibrates in the glycerolipid matrix, increase the absorption of these compounds into lymphatic system, and increase the availability of these compounds to their therapeutic targets.

[0034] The natural digestive process relies on the secretion of bile into ingested intestinal contents and their mixing with the intestinal contents to initiate access to other digestive processes, such as emulsification and lipase activity. These processes must be completed for a drug to be absorbed. A complete gallbladder response associated with lipid ingestion secretes up to 50-60 mL of bile into the duodenum. The present invention relies on the intimate mixing of a digestive enhancer with a fibrate in the preparation of the pharmaceutical compositions disclosed herein, which can then be orally ingested by the patient. The fibrate is then presented to the intestinal lumen in a form ready for immediate ingestion. This process is highly efficient because the digestive enhancer is intimately mixed with the formulation lipid excipient. Without wishing to be limited by any theory, the pharmaceutical compositions disclosed herein use components that are products of triglyceride digestion to mimic the conditions caused by a high-fat diet. This formulation allows one or more fibrates contained therein to be encapsulated in micelles with free fatty acids, allowing them to be absorbed by absorptive epithelial cells, which then package the one or more fibrates into chylomicrons. The fibrate-loaded chylomicrons are then transported by the lymphatic system to their target cells, where the fibrates are taken up by these cells to exert their beneficial effects.In essence, chylomicrons are used as a drug delivery system for one or more fibrates contained in the pharmaceutical compositions disclosed herein.By controlling the components and amounts of one or more glycerolipids and one or more digestive enhancers, the disclosed pharmaceutical compositions provide a more consistent and predictable bioavailability of one or more fibrates disclosed herein, which can be further achieved by relying on a high-fat meal.

[0035] The pharmaceutical compositions disclosed herein are advantageous for several reasons, all of which ultimately increase the bioavailability and efficacy of one or more fibrates contained therein. For example, the pharmaceutical compositions disclosed herein deliver their fibrates via the lymphatic system. The use of the lymphatic system to deliver fibrates is beneficial for several reasons. First, the lymphatic system avoids pre-systemic metabolism, which reduces the bioavailability of many fibrates administered using traditional oral delivery approaches. Also known as the first-pass effect or first-pass metabolism, fibrates absorbed through the digestive system must first enter the hepatic portal system before reaching the systemic circulation. In the hepatic portal system, fibrates can be metabolized by hepatic enzymes in the liver, reducing the amount of fibrate that enters the systemic circulation. Thus, delivery of fibrates via the lymphatic system acts as a bypass for fibrates susceptible to hepatic metabolism. The lymphatic uptake system represents an attractive opportunity for preferential drug delivery. However, small, water-soluble molecules that follow the rules of paracellular absorption (e.g., Lipinski's rule) are not ideal substrates for lymphatic uptake. Even when absorbed via lymphatic uptake, additional highly lipophilic molecules often have poor and variable bioavailability. The present invention utilizes a broad family of digestion-enhancing agents in lipid delivery systems to enable both small, Lipinski-compatible drugs and highly lipophilic drugs to be effectively delivered via the lymphatic uptake pathway.

[0036] Furthermore, lymphatic administration routes can facilitate direct delivery of fibrates to their target cells, thereby increasing their bioavailability and reducing their clearance rate. For example, fibrate-loaded chylomicrons transported into the lymphatic system are drained into the thoracic arteries and circulate throughout the body via the arterial system to reach capillary beds, where they are extravasated into surrounding tissues and taken up by target cells. Fibrate-loaded chylomicrons that are not taken up by target cells and removed from the extracellular environment by interstitial fluid are then taken up by lacteals, transported via the lymphatic system, and drained into the thoracic arteries, where they are recirculated throughout the body. Such lymphatic-based administration allows greater delivery of fibrates to various systems, organs, and tissues due to the avoidance of the hepatic portal vein system. Furthermore, as more of the fibrate enters the general circulation, its elimination, ie, metabolism and excretion, is prolonged, thereby slowing the clearance rate of the compound and effectively increasing its half-life.

[0037] Another advantage of the disclosed pharmaceutical compositions is the use of chylomicrons to selectively biodistribute one or more fibrates contained therein to immune cells, such as macrophages and dendritic cells. For example, there are several processes by which macrophages can ingest chylomicrons. First, macrophages circulating in the lymph and blood secrete lipoprotein lipase, and chylomicrons are the substrate for this enzymatic activity, resulting in the uptake of chylomicron proteins and lipids, and thus any fibrates contained within the chylomicrons. Furthermore, the extrinsic lipoprotein metabolic pathway, through a series of processing events, converts chylomicrons into LDL particles, which are oxidized by ROS to generate oxidized LDL particles. The FAT / CD36 scavenger receptor located on the membrane of macrophages binds to and endocytoses these oxidized LDL particles, including any fibrates contained therein. Finally, these fibrate-loaded macrophages are directed to cells undergoing pathological damage, where the fibrates can be delivered to these damaged cells.

[0038] Furthermore, when processed into micelles in the small intestine, the components of the disclosed pharmaceutical compositions are believed to mimic pathogen-associated molecular patterns (PAMPs). Absorption of these micelles by the gut-associated lymphoid tissue (GALT) of the small intestine leads to subsequent uptake by immune cells such as macrophages and dendritic cells through a pattern recognition receptor-mediated process. Additionally, because these micelles share structural similarities with chylomicrons, it is believed that these micelles may also be taken up via the macrophage lipoprotein lipase process described above.

[0039] The disclosed pharmaceutical compositions are also advantageous because the ingredients used in their formulations mimic signals that induce bile and pancreatic lipoprotein lipase secretion, increasing the rate of micelle formation and enhancing the rate of epithelial cell absorption of the micelles beyond that achieved by the use of digestive enhancers in the formulation alone. Such characteristics increase the rate and amount of fibrate that enters the lymphatic system and, therefore, its bioavailability.

[0040] In addition to preferential uptake into the lymphatic system and selective biodistribution to immune cells, the disclosed pharmaceutical compositions have several additional advantages.For example, fibrates are poorly water-soluble or hydrophobic therapeutic compounds, and have been found to be difficult to formulate in a therapeutically effective manner due to, for example, insolubility or instability in solution, which leads to precipitation.Moreover, it has surprisingly been found that significantly higher concentrations of fibrates can be formulated into the pharmaceutical compositions disclosed herein compared to currently known formulations.Furthermore, the disclosed pharmaceutical compositions comprising one or more fibrates dramatically increase the dissolution rate and bioavailability of these compounds.

[0041] Yet another advantage of the disclosed pharmaceutical compositions is the enhanced specificity of one or more fibrates for their cellular targets. Chylomicrons contain membrane-bound proteins that function as ligands for their cognate receptors located on the membrane surface of cells. One such ligand for these large lipoprotein particles is a protein that interacts with lipid transfer proteins. When fibrate-loaded chylomicrons are shed for absorption, cells that express high levels of lipid transfer proteins on their cell membranes preferentially bind and internalize these lipoprotein particles. For example, the brain has high levels of lipid transfer proteins on its cell membrane, allowing it to cross the blood-brain barrier and other epithelial tissues, such as the choroid plexus. This mechanism thereby increases the efficacy of these compounds. Other cells that express high levels of lipid transfer proteins on their cell membranes include immune cells, cardiac cells, adipocytes, liver cells, and cancer cells. Cardiac cells express high levels of lipid transfer proteins on their surface, and therefore, the inventors may expect increased cardiotoxicity for therapeutic compounds delivered via the lymphatic route. However, cardiotoxicity of therapeutic compounds is generally associated with high C maxHigh concentrations of free compounds can lead to GPCR- or ion channel-related pathology. Surprisingly, lipid delivery of therapeutic compounds can result in lower cardiac toxicity than expected, as these targets are protected from high concentrations of free compounds because they are released only slowly from the chylomicron phase. Therefore, the use of the pharmaceutical compositions disclosed herein can also be associated with reduced cardiac side effects and reduced toxicity. Furthermore, upon ingestion, the therapeutic compounds remain embedded in the oily / fatty excipient, limiting the opportunity for the compounds to solubilize in aqueous intestinal contents, thereby avoiding contact toxicity, such as gastric erosion and other local damage or harm. In addition to avoiding first-pass metabolism and local toxicity, enhanced uptake through the lymphatic pathway also minimizes the exposure and availability of free therapeutic compounds further down the digestive tract. In this way, interactions and disruption of the gut microbiota can be minimized. This is particularly beneficial when using this technology with antibacterial agents. Furthermore, the anatomical structure of the lymphatic system allows for effective targeting of the lungs with appropriate drugs. For example, anti-inflammatory, anti-fibrotic, anti-bacterial and bronchodilator drugs can be considered for ling targeting with lymphatic delivery using this technology.

[0042] Furthermore, the disclosed pharmaceutical compositions differ from current surfactant-based formulations, such as macroemulsions, microemulsions, self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), self-nanoemulsifying drug delivery systems (SNEDDS), solid lipid nanoparticles (SLN), liposomes, and lipoplexes. The disclosed pharmaceutical compositions are not emulsions or self-emulsifying compositions and therefore avoid the side effects associated with these formulations, such as destabilizing the stomach lining and causing irritation. Furthermore, the disclosed pharmaceutical compositions avoid manufacturing issues associated with current surfactant-based formulations, such as formulation handling problems and the lack of predictive in vitro testing. The disclosed pharmaceutical compositions also avoid issues associated with current surfactant-based formulations, including in vivo drug precipitation, limited lymphatic uptake, and the lack and oxidation of unsaturated fatty acids. Surprisingly, by mimicking the microenvironment of mixed micelles, the disclosed pharmaceutical compositions completely bypass the dissolution phase of drug uptake, resulting in significantly higher bioavailability of one or more fibrates contained therein. Unlike the self-emulsifying systems described above, the formulations disclosed herein are designed to avoid the formation of stable emulsions and do not undergo spontaneous emulsification when added to water (exhibiting the ouzo effect). Rather, when added to water, these materials are apparently immiscible.

[0043] Pharmaceutical Composition Aspects of the present specification partially disclose compositions. The compositions disclosed herein are generally administered as pharmaceutically acceptable compositions. As used herein, the term "pharmaceutically acceptable" refers to any molecular entity or composition useful for preparing pharmaceutical compositions that are generally safe, non-toxic, and not biologically or otherwise undesirable, including those acceptable for veterinary and human pharmaceutical use. As used herein, the term "pharmaceutically acceptable composition" is synonymous with "pharmaceutical composition" and refers to a combination of one or more fibrates disclosed herein combined with one or more glycerolipids, one or more digestive aids, and other ingredients disclosed herein to form a product administered to an individual. The pharmaceutical compositions disclosed herein are useful for medical and veterinary applications. The pharmaceutical compositions may be administered to an individual alone or in combination with other supplementary active ingredients, agents, drugs, or hormones.

[0044] The present specification discloses pharmaceutical compositions useful for formulating one or more fibrates. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more glycerolipids, and c) one or more digestive enhancers. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more glycerolipids, c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24 In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more glycerolipids, c) one or more bile acids and / or one or more bile salts, and d) one or more phospholipids. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more glycerolipids, c) one or more bile acids and / or one or more bile salts, d) one or more phospholipids, and e) one or more free C 14-24 Contains fatty acid surfactants.

[0045] In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more partially hydrolyzed glycerolipids including one or more triglycerides, a mixture of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, and c) one or more digestive enhancers. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more partially hydrolyzed glycerolipids including one or more triglycerides, a mixture of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24 In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more partially hydrolyzed glycerolipids comprising one or more triglycerides, a mixture of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and / or one or more bile salts, and d) one or more phospholipids. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more partially hydrolyzed glycerolipids comprising one or more triglycerides, a mixture of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and / or one or more bile salts, d) one or more phospholipids, and e) one or more free C 14-24 Contains fatty acid surfactants.

[0046] In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, and c) one or more digestive enhancers. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24 In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, c) one or more bile acids and / or one or more bile salts, and d) one or more phospholipids. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, c) one or more bile acids and / or one or more bile salts, d) one or more phospholipids, and e) one or more free C 14-24 Contains fatty acid surfactants.

[0047] The pharmaceutical compositions disclosed herein are formulated as anhydrous solids, solid dispersions, or molecular dispersions. Therefore, the formulations of the disclosed pharmaceutical compositions do not contain any water. Furthermore, as mentioned above, the disclosed pharmaceutical compositions are not emulsions or self-emulsifying compositions. Therefore, the pharmaceutical compositions disclosed herein behave like fats and oils in an aqueous environment, maintaining their hydrophobic lipid characteristics when the lipid digestion process requires disintegration for absorption. Emulsification occurs only when exposed to pancreatic juice from the small intestine. One reason is that the one or more glycerolipids and one or more digestive enhancers used are not sufficiently amphiphilic to initiate emulsification, and these components require the action of bile secreted by the gallbladder during the digestive process to contribute to the formation of micellar structures. Another reason is that the bile acids, fatty acid surfactants, phospholipids, and any other digestive enhancers, individually and in combination, are all below the critical micelle concentration required for emulsification to occur.

[0048] Fibrates Embodiments of the present specification partially disclose fibrates. Examples of suitable fibrates include, but are not limited to, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, and simfibrate. Fibrates are more lipophilic or hydrophobic; bezafibrate has a logP of 4.0, ciprofibrate has a logP of 3.6, clinofibrate has a logP of 7.5, clofibrate has a logP of 3.4, clofibrate has a logP of 2.8, etofibrate has a logP of 3.5, fenofibrate has a logP of 5.3, fenofibric acid has a logP of 4.4, gemfibrozil has a logP of 4.4, nafenopin has a logP of 4.9, lonifibrate has a logP of 3.9, and simfibrate has a logP of 6.2. [ka]

[0049] Other fibrates, such as bezafibrate, ciprofibrate, and gemfibrozil, exist in their acid form, but like fenofibrate, clofibrate, lonifibrate, and simfibrate, they are fibric acid derivative esters. In addition to being a PPARα agonist, bezafibrate may also have some agonist activity at PPARγ and PPARδ. [ka]

[0050] In one embodiment, a pharmaceutical composition disclosed herein comprises one or more fibrates in an amount, e.g., about 0.05%, about 0.1%, about 1%, about 2.5%, about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, about 20%, about 22.5%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50% by weight. In one embodiment, a pharmaceutical composition disclosed herein comprises one or more fibrates in an amount, e.g., at least 0.05% by weight, at least 0.1% by weight, at least 1% by weight, at least 2.5% by weight, at least 5% by weight, at least 7.5% by weight, at least 10% by weight, at least 12.5% ​​by weight, at least 15% by weight, at least 17.5% by weight, at least 20% by weight, at least 22.5% by weight, at least 25% by weight, at least 30% by weight, at least 35% by weight, at least 40% by weight, at least 45% by weight, or at least 50% by weight. In one embodiment, a pharmaceutical composition disclosed herein comprises one or more fibrates in an amount, e.g., up to 0.05%, up to 0.1%, up to 1%, up to 2.5%, up to 5%, up to 7.5%, up to 10%, up to 12.5%, up to 15%, up to 17.5%, up to 20%, up to 22.5%, up to 25%, up to 30%, up to 35%, up to 40%, up to 45%, or up to 50% by weight.

[0051] In one embodiment, the pharmaceutical compositions disclosed herein may contain, for example, about 0.05% to about 1%, about 0.05% to about 2.5%, about 0.05% to about 5%, about 0.05% to about 7.5%, about 0.05% to about 10%, about 0.05% to about 12.5%, about 0.05% to about 15%, about 0.05% to about 17.5%, about 0.05% to about 20%, about 0.05% to about 22.5%, about 0.05% to about 2 5%, about 0.05% to about 30%, about 0.05% to about 40%, about 0.05% to about 50%, about 0.1% to about 1%, about 0.1% to about 2.5%, about 0.1% to about 5%, about 0.1% to about 7.5%, about 0.1% to about 10%, about 0.1% to about 12.5%, about 0.1% to about 15%, about 0.1% to about 17.5%, about 0.1% to about 20%, about 0.1% to about 22.5%, about 0.1% to about 25% , about 0.1% to about 30%, about 0.1% to about 40%, about 0.1% to about 50%, about 1% to about 2.5%, about 1% to about 5%, about 1% to about 7.5%, about 1% to about 10%, about 1% to about 12.5%, about 1% to about 15%, about 1% to about 17.5%, about 1% to about 20%, about 1% to about 22.5%, about 1% to about 25%, about 1% to about 30%, about 1% to about 40%, about 1% to about 50%, about 5% to about 1 Contains one or more fibrates in an amount of 0%, about 5% to about 20%, about 5% to about 30%, about 5% to about 40%, about 5% to about 50%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 30% to about 40%, about 30% to about 50%, or about 40% to about 50% (by weight).

[0052] In one embodiment, the pharmaceutical compositions disclosed herein comprise one or more fibrates at a concentration of, for example, about 10 mg / mL, about 15 mg / mL, about 20 mg / mL, about 25 mg / mL, about 30 mg / mL, about 35 mg / mL, about 40 mg / mL, about 45 mg / mL, about 50 mg / mL, about 60 mg / mL, about 65 mg / mL, about 70 mg / mL, about 75 mg / mL, about 100 mg / mL, about 125 mg / mL, about 150 mg / mL, about 175 mg / mL, about 200 mg / mL, about 225 mg / mL, about 250 mg / mL, about 275 mg / mL, or about 300 mg / mL. In one embodiment, the pharmaceutical compositions disclosed herein comprise one or more fibrates in a concentration of, for example, at least 10 mg / mL, at least 15 mg / mL, at least 20 mg / mL, at least 25 mg / mL, at least 30 mg / mL, at least 35 mg / mL, at least 40 mg / mL, at least 45 mg / mL, at least 50 mg / mL, at least 60 mg / mL, at least 65 mg / mL, at least 70 mg / mL, at least 75 mg / mL, at least 100 mg / mL, at least 125 mg / mL, at least 150 mg / mL, at least 175 mg / mL, at least 200 mg / mL, at least 225 mg / mL, at least 250 mg / mL, at least 275 mg / mL, or at least 300 mg / mL. In one embodiment, a pharmaceutical composition disclosed herein comprises one or more fibrates in a concentration of, for example, up to 10 mg / mL, up to 15 mg / mL, up to 20 mg / mL, up to 25 mg / mL, up to 30 mg / mL, up to 35 mg / mL, up to 40 mg / mL, up to 45 mg / mL, up to 50 mg / mL, up to 60 mg / mL, up to 65 mg / mL, up to 70 mg / mL, up to 75 mg / mL, up to 100 mg / mL, up to 125 mg / mL, up to 150 mg / mL, up to 175 mg / mL, up to 200 mg / mL, up to 225 mg / mL, up to 250 mg / mL, up to 275 mg / mL, or up to 300 mg / mL.

[0053] In one embodiment, the pharmaceutical composition disclosed herein may contain, for example, about 10 mg / mL to about 25 mg / mL, about 10 mg / mL to about 50 mg / mL, about 10 mg / mL to about 75 mg / mL, about 10 mg / mL to about 100 mg / mL, about 10 mg / mL to about 125 mg / mL, about 10 mg / mL to about 150 mg / mL, about 10 mg / mL to about 200 mg / mL, about 10 mg / mL to about 250 mg / mL, about 10 mg / mL to about 300 mg / mL, about 25 mg / mL to about 50 mg / mL, about 25 mg / mL to about 75 mg / mL, about 25 mg / mL to about 100 mg / mL, about 25 mg / mL to about 125 mg / mL, about 25 mg / mL to about 150 mg / mL, about 25 mg / mL to about 200 mg / mL, about 25 mg / mL~about 250mg / mL, about 25mg / mL~about 300mg / mL, about 50mg / mL~about 100mg / mL, about 50mg / mL~about 150mg / mL, about 50mg / mL~about 200mg / mL, about 50mg / mL~about 250mg / mL, about 50mg / mL to about 300mg / mL, about 75mg / mL to about 100mg / mL, about 75mg / mL to about 150mg / mL, about 75mg / mL to about 200mg / mL, about 75mg / mL to about 250mg / mL, about 75mg / mL~about 300mg / mL, about 100mg / mL~about 150mg / mL, about 100mg / mL~about 200mg / mL, about 100mg / mL~about 250mg / mL, about 100mg / mL~about 300mg / mL, about 125mg / mL~about Contains one or more fibrates at a concentration of 150 mg / mL, about 125 mg / mL to about 200 mg / mL, about 125 mg / mL to about 250 mg / mL, about 125 mg / mL to about 300 mg / mL, about 150 mg / mL to about 200 mg / mL, about 150 mg / mL to about 250 mg / mL, about 150 mg / mL to about 300 mg / mL, about 200 mg / mL to about 250 mg / mL, about 200 mg / mL to about 300 mg / mL, or about 250 mg / mL to about 300 mg / mL.

[0054] Glycerolipids The pharmaceutical compositions disclosed herein may contain one or more glycerolipids. Glycerolipids are hydrophobic molecules mainly composed of mono-, di-, and tri-substituted glycerols, with an HLB of less than 4. One group of glycerolipids is glycerides, in which one, two, or all three hydroxyl groups of glycerol are esterified with fatty acids to produce monoglycerides, diglycerides, and triglycerides, respectively. In these compounds, each hydroxyl group of glycerol may be esterified with the same or different fatty acids. In some embodiments, the monoglycerides disclosed herein are C 12 -C 24 In some embodiments, the diglycerides disclosed herein may comprise saturated or unsaturated fatty acids having a carbon length of C 12 -C 24 one saturated or unsaturated fatty acid with a carbon length of C 12 -C 24 In some embodiments, the triglycerides disclosed herein may comprise two saturated or unsaturated fatty acids having a carbon length of C 12 -C 24 one saturated or unsaturated fatty acid with a carbon length of C 12 -C 24 Two saturated or unsaturated fatty acids with a carbon length of C 12 -C 24 The fatty acid may contain three saturated or unsaturated fatty acids having a carbon length of 1 to 3.

[0055] Two types of glycerolipids are used when formulating one or more fibrates disclosed herein to produce the pharmaceutical compositions disclosed herein. One type is hard fat, i.e., glycerolipids that are solid at 18°C. The disclosed hard fats or glycerolipids that are solid at 18°C ​​have several purposes. During the formulation process of the pharmaceutical compositions disclosed herein, the hard fats form complexes with the fibrates disclosed herein, stabilizing them in the glycerolipid matrix, thereby preventing the compounds from precipitating. Furthermore, during administration of the pharmaceutical compositions disclosed herein, the hard fats disclosed herein induce the lipid digestion process, stimulating the release of bile from the gallbladder and enhancing the emulsification of the administered pharmaceutical composition. Furthermore, the hard fats present in the pharmaceutical composition serve as substrates for pancreatic lipase, which breaks down these hard fats into glycerol and free fatty acids. The presence of these digested lipid molecules, along with the associated fibrates, triggers their absorption by the absorptive epithelial cells lining the lumen of the duodenum of the small intestine. Once internalized, the absorptive epithelial cells then process the free fatty acid / fibrate mixture and distribute it to the lymphatic system. The disclosed hard fats or glycerolipids that are solid at 18°C ​​do not have emulsion-forming properties because these lipids do not exhibit a critical micelle concentration. Therefore, another purpose of the disclosed hard fats or glycerolipids that are solid at 18°C ​​is to prevent formulation ingredients with a critical micelle concentration from initiating emulsification by diluting these ingredients below their critical micelle concentration and providing an anhydrous environment that reduces the necessary interaction between these ingredients to initiate emulsification.

[0056] Another type of glycerolipid used in formulating one or more fibrates disclosed herein is a liquid fat or oil, i.e., a glycerolipid that is liquid at 18°C. The primary purpose of the disclosed liquid fat or glycerolipid that is liquid at 18°C ​​is as a solvent to promote dissolution of the disclosed fibrates and as a stabilizer to prevent the disclosed fibrates from precipitating from the glycerolipid matrix. The disclosed liquid fat or glycerolipid that is liquid at 18°C ​​does not have emulsion-forming properties because these lipids do not exhibit a critical micelle concentration. Therefore, another purpose of the disclosed liquid fat or glycerolipid that is liquid at 18°C ​​is to prevent formulation ingredients with a critical micelle concentration from initiating emulsification by diluting these ingredients below their critical micelle concentration and providing an anhydrous environment that reduces the necessary interaction between these ingredients to initiate emulsification.

[0057] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more glycerolipids in an amount of, for example, about 20% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), about 60% (by weight), about 65% (by weight), about 70% (by weight), about 75% (by weight), about 80% (by weight), about 85% (by weight), about 90% (by weight), or about 95% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more glycerolipids in an amount, e.g., at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), at least 75% (by weight), at least 80% (by weight), at least 85% (by weight), at least 90% (by weight), or at least 95% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more glycerolipids in an amount, e.g., up to 20% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), up to 75% (by weight), up to 80% (by weight), up to 85% (by weight), up to 90% (by weight), up to 95% (by weight), or up to 99% (by weight).

[0058] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 25% to about 30%, about 25% to about 40%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 70%, about 25% to about 80%, about 25% to about 90%, about 30% to about 40%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 70%, about 30 ...30% to about 90%, about 30% to about 40%, about 30% to about 55%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, about 30% to about 40%, about 30% to about 55%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, about 30% to about 40%, about 30% to about 55%, about 30% to about 0%, about 30% to about 80%, about 30% to about 90%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 40% to about 75%, about 40% to about 80%, about 40% to about 85%, about 40% to about 90%, about 40% to about 95%, about 45% to about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 45% to about 75%, about 45% to about 80%, about 45% to about 85%, about 45% to about 90%, about 45% to about 95%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65 %, about 50% to about 70%, about 50% to about 75%, about 50% to about 80%, about 50% to about 85%, about 50% to about 90%, about 50% to about 95%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 55% to about 75%, about 55% to about 80%, about 55% to about 85%, about 55% to about 90%, about 55% to about 95%, about 60% to about 65%, about 60% to about 70%, about 60% to about 75%, about 60% to about 80%, about 60% to about 85%, about 60% to about 90%, about 60% to about 95%, about 65% to about 70%, about 65% to about 75%, about 65% to about 80% , about 65% to about 85%, about 65% to about 90%, about 65% to about 95%, about 70% to about 75%, about 70% to about 80%, about 70% to about 85%, about 70% to about 90%, about 70% to about 95%, about 75% to about 80%, about 75% to about 85%, about 75% to about 90%, about 75% to about 95%, about 80% to about 85%, about 80% to about 90%, about 80% to about 95%, about 80% to about 99%, about 85% to about 90%, about 85% to about 95%, about 85% to about 99%, about 90% to about 95%, or about 90% to about 99% (by weight).

[0059] In some embodiments, the pharmaceutical compositions disclosed herein comprise a saturated C 10 -C 18 Mixture of triglycerides, saturated C 10 -C 20 Mixture of triglycerides, saturated C 10 -C 22 Mixture of triglycerides, saturated C 10 -C 24 Mixture of triglycerides, saturated C 12 -C 18 Mixture of triglycerides, saturated C 12 -C 20 Mixture of triglycerides, saturated C 12 -C 22 Mixture of triglycerides, saturated C 12 -C 24 Mixture of triglycerides, saturated C 14 -C 18 Mixture of triglycerides, saturated C 14 -C 20 Mixture of triglycerides, saturated C 14 -C 22 Mixture of triglycerides, saturated C 14 -C 24 Mixture of triglycerides, saturated C 16 -C 18 Mixture of triglycerides, saturated C 16 -C 20 Mixture of triglycerides, saturated C 16 -C 22 Mixture of triglycerides, saturated C 16 -C 24 Mixture of triglycerides, saturated C 18 -C 20 Mixture of triglycerides, saturated C 18 -C 22 Mixture of triglycerides, saturated C 18 -C 24 Mixture of triglycerides, saturated C 20 -C 22 Mixture of triglycerides, or saturated C 22 -C 24It may also comprise one or more hard fats or glycerolipids that are solid at 18°C, comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0060] In some embodiments, the pharmaceutical compositions disclosed herein comprise an unsaturated C 10 -C 18 Mixture of triglycerides, unsaturated C 10 -C 20 Mixture of triglycerides, unsaturated C 10 -C 22 Mixture of triglycerides, unsaturated C 10 -C 24 Mixture of triglycerides, unsaturated C 12 -C 18 Mixture of triglycerides, unsaturated C 12 -C 20 Mixture of triglycerides, unsaturated C 12 -C 22 Mixture of triglycerides, unsaturated C 12 -C 24 Mixture of triglycerides, unsaturated C 14 -C 18 Mixture of triglycerides, unsaturated C 14 -C 20 Mixture of triglycerides, unsaturated C 14 -C 22 Mixture of triglycerides, unsaturated C 14 -C 24 Mixture of triglycerides, unsaturated C 16 -C 18 Mixture of triglycerides, unsaturated C 16 -C 20 Mixture of triglycerides, unsaturated C 16 -C 22 Mixture of triglycerides, unsaturated C 16 -C 24 Mixture of triglycerides, unsaturated C 18 -C 20 Mixture of triglycerides, unsaturated C 18 -C 22 Mixture of triglycerides, unsaturated C 18 -C 24 Mixture of triglycerides, unsaturated C 20-C 22 Mixture of triglycerides, or unsaturated C 22 -C 24 It may also comprise one or more hard fats or glycerolipids that are solid at 18°C, comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0061] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated C 10 -C 18 Mixture of triglycerides, saturated and unsaturated C 10 -C 20 Mixture of triglycerides, saturated and unsaturated C 10 -C 22 Mixture of triglycerides, saturated and unsaturated C 10 -C 24 Mixture of triglycerides, saturated and unsaturated C 12 -C 18 Mixture of triglycerides, saturated and unsaturated C 12 -C 20 Mixture of triglycerides, saturated and unsaturated C 12 -C 22 Mixture of triglycerides, saturated and unsaturated C 12 -C 24 Mixture of triglycerides, saturated and unsaturated C 14 -C 18 Mixture of triglycerides, saturated and unsaturated C 14 -C 20 Mixture of triglycerides, saturated and unsaturated C 14 -C 22 Mixture of triglycerides, saturated and unsaturated C 14 -C 24 Mixture of triglycerides, saturated and unsaturated C 16 -C 18 Mixture of triglycerides, saturated and unsaturated C 16 -C 20 Mixture of triglycerides, saturated and unsaturated C 16 -C 22 Mixture of triglycerides, saturated and unsaturated C 16 -C 24Mixture of triglycerides, saturated and unsaturated C 18 -C 20 Mixture of triglycerides, saturated and unsaturated C 18 -C 22 Mixture of triglycerides, saturated and unsaturated C 18 -C 24 Mixture of triglycerides, saturated and unsaturated C 20 -C 22 A mixture of triglycerides, or saturated and unsaturated C 22 -C 24 It may also comprise one or more hard fats or glycerolipids that are solid at 18°C, comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0062] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids that are solid at 18°C, e.g., comprising, consisting essentially of, or consisting of a mixture of triglycerides having a melting point of about 25°C, about 26°C, about 27°C, about 28°C, about 29°C, about 30°C, about 31°C, about 32°C, about 33°C, about 34°C, about 35°C, about 36°C, about 37°C, about 38°C, about 39°C, about 40°C, about 41°C, about 43°C, about 43°C, about 44°C, about 45°C, about 45°C, about 47°C, about 48°C, about 49°C, or about 50°C. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids that are solid at 18°C, e.g., comprising, consisting essentially of, or consisting of a mixture of triglycerides having a melting point of at least 25°C, at least 26°C, at least 27°C, at least 28°C, at least 29°C, at least 30°C, at least 31°C, at least 32°C, at least 33°C, at least 34°C, at least 35°C, at least 36°C, at least 37°C, at least 38°C, at least 39°C, at least 40°C, at least 41°C, at least 43°C, at least 43°C, at least 44°C, at least 45°C, at least 45°C, at least 47°C, at least 48°C, at least 49°C, or at least 50°C. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids that are solid at 18°C, e.g., comprising, consisting essentially of, or consisting of a mixture of triglycerides having a melting point of at most 25°C, at most 26°C, at most 27°C, at most 28°C, at most 29°C, at most 30°C, at most 31°C, at most 32°C, at most 33°C, at most 34°C, at most 35°C, at most 36°C, at most 37°C, at most 38°C, at most 39°C, at most 40°C, at most 41°C, at most 43°C, at most 43°C, at most 44°C, at most 45°C, at most 45°C, at most 47°C, at most 48°C, at most 49°C, or at most 50°C.

[0063] In some embodiments, the pharmaceutical compositions disclosed herein can be administered at temperatures ranging from about 25°C to about 37°C, about 25°C to about 38°C, about 25°C to about 39°C, about 25°C to about 40°C, about 25°C to about 41°C, about 25°C to about 42°C, about 25°C to about 43°C, about 25°C to about 44°C, about 25°C to about 45°C, about 25°C to about 46°C, about 25°C to about 47°C, about 25°C to about 48°C, about 25°C to about 49°C, about 25°C to about 50°C, about 28°C to about 37°C, about 28°C to about 38°C, about 28°C to about 39°C, about 28°C to about 40°C, about 28°C to about 41°C, about 28°C to about 42°C, about 28°C to about 4 3°C, about 28°C to about 44°C, about 28°C to about 45°C, about 28°C to about 46°C, about 28°C to about 47°C, about 28°C to about 48°C, about 28°C to about 49°C, about 28°C to about 50°C, about 30°C to about 37°C, about 30°C to about 38°C, about 30°C to about 39°C, about 30°C to about 40°C, about 30°C to about 41°C, about 30°C to about 42°C, about 30°C to about 43°C, about 30°C to about 44°C, about 30°C to about 45°C, about 30°C to about 46°C, about 30°C to about 47°C, about 30°C to about 48°C, about 30°C to about 49°C, about 30°C to about 50°C, about 32°C to about 44°C, about 32°C to about 45°C, about 32°C to about 4 6°C, about 32°C to about 47°C, about 32°C to about 48°C, about 32°C to about 49°C, about 32°C to about 50°C, about 34°C to about 44°C, about 34°C to about 45°C, about 34°C to about 46°C, about 34°C to about 47°C, about 34°C to about 48°C, about 34°C to about 49°C, about 34°C to about 50°C, about 36°C to about 44°C, about 36°C to about 45°C, about 36°C to about 46°C, about 36°C to about 47°C, about 36°C to about 48°C, about 36°C to about 49°C, about 36°C to about 50°C, about 38°C to about 44°C, about 38°C to about 45°C, about 38°C to about 46°C, about 38°C to about 47°C, about 38°C to about 48°C, about 38°C to about 4 The composition may comprise one or more hard fats or glycerolipids that are solid at 18°C, comprising, consisting essentially of, or consisting of a mixture of triglycerides having a melting point of about 9°C, about 38°C to about 50°C, about 40°C to about 44°C, about 40°C to about 45°C, about 40°C to about 46°C, about 40°C to about 47°C, about 40°C to about 48°C, about 40°C to about 49°C, about 40°C to about 50°C, about 42°C to about 44°C, about 42°C to about 45°C, about 42°C to about 46°C, about 42°C to about 47°C, about 42°C to about 48°C, about 42°C to about 49°C, or about 42°C to about 50°C.

[0064] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids that are solid at 18° C., comprising, consisting essentially of, or consisting of a mixture of triglycerides in an amount of, for example, about 10% (by weight), about 15% (by weight), about 20% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), about 60% (by weight), about 65% (by weight), about 70% (by weight), or about 75% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids that are solid at 18° C., comprising, consisting essentially of, or consisting of a mixture of triglycerides in an amount, e.g., at least 10% (by weight), at least 15% (by weight), at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), or at least 75% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerolipids that are solid at 18° C., comprising, consisting essentially of, or consisting of a mixture of triglycerides in an amount, e.g., up to 10% (by weight), up to 15% (by weight), up to 20% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), or up to 75% (by weight).

[0065] In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 10% to about 65%, about 10% to about 70%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, About 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30 % to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 45% to about 50%, about 45% to about The composition may comprise one or more hard fats or glycerolipids that are solid at 18°C, comprising, consisting essentially of, or consisting of a mixture of triglycerides in an amount by weight of 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 60% to about 65%, about 60% to about 70%, or about 65% to about 70%.

[0066] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that comprise, consist essentially of, or consist of a mixture of mono-, di-, and triglycerides and are liquid at 18° C. In some embodiments, the pharmaceutical compositions disclosed herein comprise one or more liquid fats or glycerolipids that are liquid at 18° C. and comprise, consist essentially of, or consist of a mixture of mono-, di-, and triglycerides. 10 -C 18 Monoglyceride, C 10 -C 18 Diglycerides and C 10 -C 18 Mixture of triglycerides, unsaturated C 10 -C 20 Monoglyceride, C 10 -C 20 Diglycerides and C 10 -C 20 Mixture of triglycerides, unsaturated C 10 -C 22 Monoglyceride, C 10 -C 22 Diglycerides and C 10 -C 22 Mixture of triglycerides, unsaturated C 10 -C 24 Monoglyceride, C 10 -C 24 Diglycerides and C 10 -C 24 Mixture of triglycerides, unsaturated C 12 -C 18 Monoglyceride, C 12 -C 18 Diglycerides and C 12 -C 18 Mixture of triglycerides, unsaturated C 12 -C 20 Monoglyceride, C 12 -C 20 Diglycerides and C 12 -C 20 Mixture of triglycerides, unsaturated C 12 -C 22 Monoglyceride, C 12 -C 22 Diglycerides and C 12 -C 22 Mixture of triglycerides, unsaturated C 12 -C24 Monoglyceride, C 12 -C 24 Diglycerides and C 12 -C 24 Mixture of triglycerides, unsaturated C 14 -C 18 Monoglyceride, C 14 -C 18 Diglycerides and C 14 -C 18 Mixture of triglycerides, unsaturated C 14 -C 20 Monoglyceride, C 14 -C 20 Diglycerides and C 14 -C 20 Mixture of triglycerides, unsaturated C 14 -C 22 Monoglyceride, C 14 -C 22 Diglycerides and C 14 -C 22 Mixture of triglycerides, unsaturated C 14 -C 24 Monoglyceride, C 14 -C 24 Diglycerides and C 14 -C 24 Mixture of triglycerides, unsaturated C 16 -C 18 Monoglyceride, C 16 -C 18 Diglycerides and C 16 -C 18 Mixture of triglycerides, unsaturated C 16 -C 20 Monoglyceride, C 16 -C 20 Diglycerides and C 16 -C 20 Mixture of triglycerides, unsaturated C 16 -C 22 Monoglyceride, C 16 -C 22 Diglycerides and C 16 -C 22 Mixture of triglycerides, unsaturated C 16 -C 24 Monoglyceride, C 16 -C 24Diglycerides and C 16 -C 24 Mixture of triglycerides, unsaturated C 18 -C 20 Monoglyceride, C 18 -C 20 Diglycerides and C 18 -C 20 Mixture of triglycerides, unsaturated C 18 -C 22 Monoglyceride, C 18 -C 22 Diglycerides and C 18 -C 22 Mixture of triglycerides, unsaturated C 18 -C 24 Monoglyceride, C 18 -C 24 Diglycerides and C 18 -C 24 Mixture of triglycerides, unsaturated C 20 -C 22 Monoglyceride, C 20 -C 22 Diglyceride, C 20 -C 22 Mixture of triglycerides, or unsaturated C 22 -C 24 Monoglyceride, C 22 -C 24 Diglycerides and C 22 -C 24 It may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0067] In some embodiments, the pharmaceutical compositions disclosed herein comprise a saturated C 10 -C 18 Monoglyceride, C 10 -C 18 Diglycerides and C 10 -C 18 Mixture of triglycerides, saturated C 10 -C 20 Monoglyceride, C 10 -C 20 Diglycerides and C 10 -C20 Mixture of triglycerides, saturated C 10 -C 22 Monoglyceride, C 10 -C 22 Diglycerides and C 10 -C 22 Mixture of triglycerides, saturated C 10 -C 24 Monoglyceride, C 10 -C 24 Diglycerides and C 10 -C 24 Mixture of triglycerides, saturated C 12 -C 18 Monoglyceride, C 12 -C 18 Diglycerides and C 12 -C 18 Mixture of triglycerides, saturated C 12 -C 20 Monoglyceride, C 12 -C 20 Diglycerides and C 12 -C 20 Mixture of triglycerides, saturated C 12 -C 22 Monoglyceride, C 12 -C 22 Diglycerides and C 12 -C 22 Mixture of triglycerides, saturated C 12 -C 24 Monoglyceride, C 12 -C 24 Diglycerides and C 12 -C 24 Mixture of triglycerides, saturated C 14 -C 18 Monoglyceride, C 14 -C 18 Diglycerides and C 14 -C 18 Mixture of triglycerides, saturated C 14 -C 20 Monoglyceride, C 14 -C 20 Diglycerides and C 14 -C 20 Mixture of triglycerides, saturated C 14 -C 22Monoglyceride, C 14 -C 22 Diglycerides and C 14 -C 22 Mixture of triglycerides, saturated C 14 -C 24 Monoglyceride, C 14 -C 24 Diglycerides and C 14 -C 24 Mixture of triglycerides, saturated C 16 -C 18 Monoglyceride, C 16 -C 18 Diglycerides and C 16 -C 18 Mixture of triglycerides, saturated C 16 -C 20 Monoglyceride, C 16 -C 20 Diglycerides and C 16 -C 20 Mixture of triglycerides, saturated C 16 -C 22 Monoglyceride, C 16 -C 22 Diglycerides and C 16 -C 22 Mixture of triglycerides, saturated C 16 -C 24 Monoglyceride, C 16 -C 24 Diglycerides and C 16 -C 24 Mixture of triglycerides, saturated C 18 -C 20 Monoglyceride, C 18 -C 20 Diglycerides and C 18 -C 20 Mixture of triglycerides, saturated C 18 -C 22 Monoglyceride, C 18 -C 22 Diglycerides and C 18 -C 22 Mixture of triglycerides, saturated C 18 -C 24 Monoglyceride, C 18 -C 24 Diglycerides and C18 -C 24 Mixture of triglycerides, saturated C 20 -C 22 Monoglyceride, C 20 -C 22 Diglyceride, C 20 -C 22 Mixture of triglycerides, or saturated C 22 -C 24 Monoglyceride, C 22 -C 24 Diglycerides and C 22 -C 24 It may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0068] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated C 10 -C 18 Monoglyceride, C 10 -C 18 Diglycerides and C 10 -C 18 Mixture of triglycerides, saturated and unsaturated C 10 -C 20 Monoglyceride, C 10 -C 20 Diglycerides and C 10 -C 20 Mixture of triglycerides, saturated and unsaturated C 10 -C 22 Monoglyceride, C 10 -C 22 Diglycerides and C 10 -C 22 Mixture of triglycerides, saturated and unsaturated C 10 -C 24 Monoglyceride, C 10 -C 24 Diglycerides and C 10 -C 24 Mixture of triglycerides, saturated and unsaturated C 12 -C 18 Monoglyceride, C 12 -C 18 Diglycerides and C 12-C 18 Mixture of triglycerides, saturated and unsaturated C 12 -C 20 Monoglyceride, C 12 -C 20 Diglycerides and C 12 -C 20 Mixture of triglycerides, saturated and unsaturated C 12 -C 22 Monoglyceride, C 12 -C 22 Diglycerides and C 12 -C 22 Mixture of triglycerides, saturated and unsaturated C 12 -C 24 Monoglyceride, C 12 -C 24 Diglycerides and C 12 -C 24 Mixture of triglycerides, saturated and unsaturated C 14 -C 18 Monoglyceride, C 14 -C 18 Diglycerides and C 14 -C 18 Mixture of triglycerides, saturated and unsaturated C 14 -C 20 Monoglyceride, C 14 -C 20 Diglycerides and C 14 -C 20 Mixture of triglycerides, saturated and unsaturated C 14 -C 22 Monoglyceride, C 14 -C 22 Diglycerides and C 14 -C 22 Mixture of triglycerides, saturated and unsaturated C 14 -C 24 Monoglyceride, C 14 -C 24 Diglycerides and C 14 -C 24 Mixture of triglycerides, saturated and unsaturated C 16 -C 18 Monoglyceride, C 16 -C 18 Diglycerides and C 16 -C18 Mixture of triglycerides, saturated and unsaturated C 16 -C 20 Monoglyceride, C 16 -C 20 Diglycerides and C 16 -C 20 Mixture of triglycerides, saturated and unsaturated C 16 -C 22 Monoglyceride, C 16 -C 22 Diglycerides and C 16 -C 22 Mixture of triglycerides, saturated and unsaturated C 16 -C 24 Monoglyceride, C 16 -C 24 Diglycerides and C 16 -C 24 Mixture of triglycerides, saturated and unsaturated C 18 -C 20 Monoglyceride, C 18 -C 20 Diglycerides and C 18 -C 20 Mixture of triglycerides, saturated and unsaturated C 18 -C 22 Monoglyceride, C 18 -C 22 Diglycerides and C 18 -C 22 Mixture of triglycerides, saturated and unsaturated C 18 -C 24 Monoglyceride, C 18 -C 24 Diglycerides and C 18 -C 24 Mixture of triglycerides, saturated and unsaturated C 20 -C 22 Monoglyceride, C 20 -C 22 Diglyceride, C 20 -C 22 A mixture of triglycerides, or saturated and unsaturated C 22 -C 24 Monoglyceride, C 22 -C 24 Diglycerides and C 22 -C24 It may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, comprising, consisting essentially of, or consisting of a mixture of triglycerides.

[0069] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, e.g., comprising, consisting essentially of, or consisting of mixtures of mono-, di-, and triglycerides having melting points of at most 15°C, at most 16°C, at most 17°C, at most 18°C, at most 19°C, or at most 20°C. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, e.g., comprising, consisting essentially of, or consisting of a mixture of mono-, di-, and triglycerides having a melting point of about 0°C to about 5°C, about 0°C to about 10°C, about 0°C to about 15°C, about 0°C to about 20°C, about 0°C to about 22°C, about 0°C to about 25°C, about 5°C to about 10°C, about 5°C to about 15°C, about 5°C to about 20°C, about 5°C to about 22°C, about 5°C to about 25°C, about 10°C to about 15°C, about 10°C to about 20°C, about 10°C to about 22°C, about 10°C to about 25°C, about 15°C to about 20°C, about 15°C to about 22°C, or about 15°C to about 25°C.

[0070] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of a mixture of mono-, di-, and / or triglycerides in an amount of, for example, about 10% (by weight), about 15% (by weight), about 20% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), about 60% (by weight), about 65% (by weight), about 70% (by weight), or about 75% (by weight). In some embodiments, a pharmaceutical composition disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount, e.g., at least 10% (by weight), at least 15% (by weight), at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), or at least 75% (by weight). In some embodiments, a pharmaceutical composition disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount, e.g., up to 10% (by weight), up to 15% (by weight), up to 20% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), or up to 75% (by weight).

[0071] In some embodiments, the pharmaceutical compositions disclosed herein may be used in a range of concentrations, for example, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 10% to about 65%, about 10% to about 70%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 10% to about 70%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 15 ... % to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30% to about 35%, About 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 45% to about 50%, about 45% to about 55%, about 45% to about 6 The composition may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, comprising, consisting essentially of, or consisting of a mixture of mono-, di-, and / or triglycerides in an amount of 0%, about 45% to about 65%, about 45% to about 70%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 60% to about 65%, about 60% to about 70%, or about 65% to about 70% (by weight).

[0072] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides. Monoglycerides include, but are not limited to, glycerol monomyristoleate, glycerol monopalmitoleate, glycerol monosapienate, glycerol monooleate, glycerol monoelaidate, glycerol monobasenate, glycerol monolinoleate, glycerol monolinolenate, glycerol monostearidonate, glycerol monoeicosenoate, glycerol monomeadate, glycerol monoarachidonate, glycerol monoeicosapentaenoate, glycerol monoerucate, glycerol monodocosahexaenoate, and glycerol mononervonate.

[0073] In some embodiments, the pharmaceutical compositions disclosed herein comprise an unsaturated C 10 -C 18 Monoglyceride, unsaturated C 10 -C 20 Monoglyceride, unsaturated C 10 -C 22 Monoglyceride, unsaturated C 10 -C 24 Monoglyceride, unsaturated C 12 -C 18 Monoglyceride, unsaturated C 12 -C 20 Monoglyceride, unsaturated C 12 -C 22 Monoglyceride, unsaturated C 12 -C 24 Monoglyceride, unsaturated C 14 -C 18 Monoglyceride, unsaturated C 14 -C 20 Monoglyceride, unsaturated C 14 -C 22 Monoglyceride, unsaturated C 14 -C 24 Monoglyceride, unsaturated C 16 -C 18Monoglyceride, unsaturated C 16 -C 20 Monoglyceride, unsaturated C 16 -C 22 Monoglyceride, unsaturated C 16 -C 24 Monoglyceride, unsaturated C 18 -C 20 Monoglyceride, unsaturated C 18 -C 22 Monoglyceride, unsaturated C 18 -C 24 Monoglyceride, unsaturated C 20 -C 22 Monoglycerides, or unsaturated C 22 -C 24 It may comprise one or more liquid fats or glycerolipids that are liquid at 18°C ​​and that comprise, consist essentially of, or consist of monoglycerides.

[0074] In some embodiments, the pharmaceutical compositions disclosed herein comprise a saturated C 10 -C 18 Monoglyceride, saturated C 10 -C 20 Monoglyceride, saturated C 10 -C 22 Monoglyceride, saturated C 10 -C 24 Monoglyceride, saturated C 12 -C 18 Monoglyceride, saturated C 12 -C 20 Monoglyceride, saturated C 12 -C 22 Monoglyceride, saturated C 12 -C 24 Monoglyceride, saturated C 14 -C 18 Monoglyceride, saturated C 14 -C 20 Monoglyceride, saturated C 14 -C 22 Monoglyceride, saturated C 14 -C 24 Monoglyceride, saturated C 16 -C 18 Monoglyceride, saturated C 16 -C20 Monoglyceride, saturated C 16 -C 22 Monoglyceride, saturated C 16 -C 24 Monoglyceride, saturated C 18 -C 20 Monoglyceride, saturated C 18 -C 22 Monoglyceride, saturated C 18 -C 24 Monoglyceride, saturated C 20 -C 22 Monoglycerides, or saturated C 22 -C 24 It may comprise one or more liquid fats or glycerolipids that are liquid at 18°C ​​and that comprise, consist essentially of, or consist of monoglycerides.

[0075] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated C 10 -C 18 Mixture of monoglycerides, saturated and unsaturated C 10 -C 20 Mixture of monoglycerides, saturated and unsaturated C 10 -C 22 Mixture of monoglycerides, saturated and unsaturated C 10 -C 24 Mixture of monoglycerides, saturated and unsaturated C 12 -C 18 Mixture of monoglycerides, saturated and unsaturated C 12 -C 20 Mixture of monoglycerides, saturated and unsaturated C 12 -C 22 Mixture of monoglycerides, saturated and unsaturated C 12 -C 24 Mixture of monoglycerides, saturated and unsaturated C 14 -C 18 Mixture of monoglycerides, saturated and unsaturated C 14 -C 20 Mixture of monoglycerides, saturated and unsaturated C 14 -C 22 Mixture of monoglycerides, saturated and unsaturated C 14 -C24 Mixture of monoglycerides, saturated and unsaturated C 16 -C 18 Mixture of monoglycerides, saturated and unsaturated C 16 -C 20 Mixture of monoglycerides, saturated and unsaturated C 16 -C 22 Mixture of monoglycerides, saturated and unsaturated C 16 -C 24 Mixture of monoglycerides, saturated and unsaturated C 18 -C 20 Mixture of monoglycerides, saturated and unsaturated C 18 -C 22 Mixture of monoglycerides, saturated and unsaturated C 18 -C 24 Mixture of monoglycerides, saturated and unsaturated C 20 -C 22 A mixture of monoglycerides, or saturated and unsaturated C 22 -C 24 It may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, comprising, consisting essentially of, or consisting of a mixture of monoglycerides.

[0076] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, e.g., that comprise, consist essentially of, or consist of monoiglycerides having a melting point of at most 15°C, at most 16°C, at most 17°C, at most 18°C, at most 19°C, or at most 20°C. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, e.g., comprising, consisting essentially of, or consisting of monoglycerides having a melting point of about 0°C to about 5°C, about 0°C to about 10°C, about 0°C to about 15°C, about 0°C to about 20°C, about 0°C to about 22°C, about 0°C to about 25°C, about 5°C to about 10°C, about 5°C to about 15°C, about 5°C to about 20°C, about 5°C to about 22°C, about 5°C to about 25°C, about 10°C to about 15°C, about 10°C to about 20°C, about 10°C to about 22°C, about 10°C to about 25°C, about 15°C to about 20°C, about 15°C to about 22°C, or about 15°C to about 25°C.

[0077] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount of, for example, about 10% (by weight), about 15% (by weight), about 20% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), or about 60% (by weight). In some embodiments, a pharmaceutical composition disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount, e.g., at least 10% (by weight), at least 15% (by weight), at least 20% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), or at least 60% (by weight). In some embodiments, a pharmaceutical composition disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount, e.g., up to 10% (by weight), up to 15% (by weight), up to 20% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), or up to 60% (by weight).

[0078] In some embodiments, the pharmaceutical compositions disclosed herein may be used in a range of concentrations, for example, about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15 ... 5% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 4 5%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 40% to about 45%, about 40% to about 50%, about 4 It may also contain one or more liquid fats or glycerolipids that are liquid at 18°C ​​and comprise, consist essentially of, or consist of one or more monoglycerides in an amount of 0% to about 55%, about 40% to about 60%, about 45% to about 50%, about 45% to about 55%, about 45% to about 60%, about 50% to about 55%, about 50% to about 60%, or about 55% to about 60% (by weight).

[0079] Commercially available hard fats or glycerolipids that are solid at 18°C ​​include cocoa butter, saturated C glycerolipids with a melting point of about 33°C, 10 -C 18 A mixture of triglycerides (GELUCIRE® 33 / 01), saturated C with a melting point of approximately 39°C 10 -C 18 A mixture of triglycerides (GELUCIRE® 39 / 01) and saturated C 10 -C 18Commercially available liquid fats or glycerolipids that are liquid at 18°C ​​include, but are not limited to, hydrolyzed corn oil with glycerol monolinoleate (MAISINE™ 35-1, MAISINE™ CC), including, but not limited to, a mixture of triglycerides (GELUCIRE® 43 / 01). In some embodiments, the hydrolyzed corn oil with glycerol monolinoleate (MAISINE™ 35-1, MAISINE™ CC) contains about 32%-52% monoglycerides, about 40%-50% diglycerides, and about 5%-30% triglycerides, including glycerol monolinoleate.

[0080] The pharmaceutical compositions disclosed herein comprise any ratio of hard fat or glycerolipid that is solid at 18° C. to liquid fat or glycerolipid that is liquid at 18° C. that stabilizes one or more fibrates disclosed herein in a manner that prevents precipitation of the one or more fibrates. In some embodiments, the pharmaceutical compositions disclosed herein comprise a ratio of hard fat or glycerolipid that is solid at 18° C. to liquid fat or glycerolipid that is liquid at 18° C. of, for example, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In some embodiments, the pharmaceutical compositions disclosed herein comprise a ratio of hard fat or glycerolipid that is solid at 18°C ​​to liquid fat or glycerolipid that is liquid at 18°C, e.g., about 5:1 to about 4:1, about 5:1 to about 3:1, about 5:1 to about 2:1, about 5:1 to about 1:1, about 4:1 to about 3:1, about 4:1 to about 2:1, about 4:1 to about 1:1, about 3:1 to about 2:1, about 3:1 to about 1:1, or about 2:1 to about 1:1.

[0081] In some embodiments, the pharmaceutical compositions disclosed herein comprise a ratio of hard fat or glycerolipid that is solid at 18° C. to liquid fat or glycerolipid that is liquid at 18° C. of, for example, about 1:5, about 1:4, about 1:3, or about 1:2. In some embodiments, the pharmaceutical compositions disclosed herein comprise a ratio of hard fat or glycerolipid that is solid at 18° C. to liquid fat or glycerolipid that is liquid at 18° C. of, for example, about 1:5 to about 1:4, about 1:5 to about 1:3, about 1:5 to about 1:2, about 1:5 to about 1:1, about 1:4 to about 1:3, about 1:4 to about 1:2, about 1:4 to about 1:1, about 1:3 to about 1:2, about 1:3 to about 1:1, or about 1:2 to about 1:1.

[0082] Digestive aid The pharmaceutical compositions disclosed herein may include one or more digestive enhancers. The primary purpose of the one or more digestive enhancers is to increase the solubility of the fibrates disclosed herein in the glycerolipid mixture, enhance absorption of the fibrates disclosed herein, thereby improving the pharmacokinetics of the compound, and / or improve the availability of the fibrates disclosed herein, promoting selected biodistribution, and thereby improving the pharmacodynamics of the compound. These improved properties are achieved by the one or more digestive enhancers creating a pre-lipid digestion formulation of the fibrates disclosed herein, which promotes and enhances the processing of one or more glycerolipids disclosed herein when the pharmaceutical compositions disclosed herein enter the duodenal region of the small intestine. Such glycerolipid processing allows one or more fibrates contained in the pharmaceutical composition to be absorbed by absorptive epithelial cells along with the digested glycerolipids, and then processed and transported to the lymphatic system. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers, including one or more bile acids. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers, including cholic acid. In some embodiments, the disclosed pharmaceutical compositions comprise one or more C 14 -C 24In some embodiments, the disclosed pharmaceutical compositions comprise one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers comprising free fatty acids. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers comprising oleic acid, steric acid, or linoleic acid. In some embodiments, the disclosed pharmaceutical compositions include one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers comprising sodium oleate, sodium stearate, and / or sodium linoleate.

[0083] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein, and 2) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acids. In some embodiments, the disclosed pharmaceutical compositions comprise 1) cholic acid as disclosed herein, and 2) one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers comprising free fatty acids. In some embodiments, the disclosed pharmaceutical compositions include 1) cholic acid as disclosed herein, and 2) one or more digestive enhancers comprising oleic acid, steric acid, or linoleic acid.

[0084] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein, 2) one or more C 14 -C 24 free fatty acids, and 3) one or more C 14 -C 24In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise one or more of: 1) cholic acid as disclosed herein; 2) one or more C 14 -C 20 free fatty acids, and 3) one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers including 1) cholic acid as disclosed herein, 2) oleic acid, steric acid, and / or linoleic acid, and 3) sodium oleate, sodium stearate, and / or sodium linoleate.

[0085] In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers including 1) one or more bile acids disclosed herein and 2) one or more phospholipids disclosed herein. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers including 1) cholic acid disclosed herein and 2) one or more phospholipids disclosed herein.

[0086] In some embodiments, the disclosed pharmaceutical compositions comprise: 1) one or more of the Cs disclosed herein; 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more C free fatty acids, and 2) one or more digestive enhancers comprising one or more phospholipids disclosed herein. 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions comprise 1) oleic acid, steric acid, and / or linoleic acid, and 2) one or more digestive enhancers comprising one or more phospholipids disclosed herein.

[0087] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein, 2) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including 1) one or more bile acids disclosed herein, 2) one or more C free fatty acids, and 3) one or more phospholipids disclosed herein. 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers comprising 1) cholic acid as disclosed herein, 2) oleic acid, steric acid, and / or linoleic acid, and 3) one or more phospholipids as disclosed herein.

[0088] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein, 2) one or more phospholipids disclosed herein, and 3) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise 1) cholic acid as disclosed herein, 2) one or more phospholipids as disclosed herein, and 3) one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise 1) cholic acid as disclosed herein, 2) one or more phospholipids as disclosed herein, and 3) a C phospholipid as disclosed herein. 14 -C 20 and one or more digestive enhancers including sodium free fatty acids. In some embodiments, the disclosed pharmaceutical compositions include 1) cholic acid as disclosed herein, 2) one or more phospholipids as disclosed herein, and 3) one or more digestive enhancers including sodium oleate, sodium stearate, and / or sodium linoleate.

[0089] In some embodiments, the disclosed pharmaceutical compositions comprise: 1) one or more of the Cs disclosed herein; 14 -C 24 free fatty acids, 2) one or more phospholipids disclosed herein, and 3) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acid surfactants. 14 -C 20 free fatty acids, 2) one or more phospholipids disclosed herein, and 3) one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise one or more of: 1) oleic acid, steric acid, and / or linoleic acid, 2) one or more phospholipids disclosed herein, and 3) one or more C phospholipids disclosed herein. 14 -C 20 and one or more digestive enhancers including a free fatty acid sodium surfactant. In some embodiments, the disclosed pharmaceutical compositions include 1) oleic acid, steric acid, and / or linoleic acid, 2) one or more phospholipids disclosed herein, and 3) one or more digestive enhancers including sodium oleate, sodium stearate, and / or sodium linoleate.

[0090] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein, 2) one or more C 14 -C 24 free fatty acids, 3) one or more phospholipids disclosed herein, and 4) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise one or more bile acids disclosed herein, one or more C 14-C 20 free fatty acids, 3) one or more phospholipids disclosed herein, and 4) one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise one or more of: 1) cholic acid as disclosed herein; 2) oleic acid, steric acid, and / or linoleic acid; 3) one or more phospholipids as disclosed herein; and 4) one or more C phospholipids as disclosed herein. 14 -C 20 and one or more digestive enhancers including a free fatty acid sodium surfactant. In some embodiments, the disclosed pharmaceutical compositions include 1) cholic acid as disclosed herein, 2) oleic acid, steric acid, and / or linoleic acid, 3) one or more phospholipids as disclosed herein, and 4) one or more digestive enhancers including sodium oleate, sodium stearate, and / or sodium linoleate.

[0091] In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of one or more digestive enhancers in an amount, e.g., about 1% (by weight), about 2.5% (by weight), about 5% (by weight), about 7.5% (by weight), about 10% (by weight), about 12.5% ​​(by weight), about 15% (by weight), about 17.5% (by weight), about 20% (by weight), about 22.5% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), about 60% (by weight), about 65% (by weight), about 70% (by weight), about 75% (by weight), or about 80% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of one or more digestive enhancers in an amount, e.g., at least 1% (by weight), at least 2.5% (by weight), at least 5% (by weight), at least 7.5% (by weight), at least 10% (by weight), at least 12.5% ​​(by weight), at least 15% (by weight), at least 17.5% (by weight), at least 20% (by weight), at least 22.5% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 45% (by weight), at least 50% (by weight), at least 55% (by weight), at least 60% (by weight), at least 65% (by weight), at least 70% (by weight), at least 75% (by weight), or at least 75% (by weight).In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of one or more digestive enhancers in an amount, e.g., up to 1% (by weight), up to 2.5% (by weight), up to 5% (by weight), up to 7.5% (by weight), up to 10% (by weight), up to 12.5% ​​(by weight), up to 15% (by weight), up to 17.5% (by weight), up to 20% (by weight), up to 22.5% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 45% (by weight), up to 50% (by weight), up to 55% (by weight), up to 60% (by weight), up to 65% (by weight), up to 70% (by weight), up to 75% (by weight), or up to 80% (by weight).

[0092] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 1% to about 2.5% (by weight), about 1% to about 5% (by weight), about 1% to about 10% (by weight), about 1% to about 15% (by weight), about 1% to about 20% (by weight), about 1% to about 25% (by weight), about 2.5% to about 5% (by weight), about 2.5% to about 10% (by weight), about 2.5% to about 15% (by weight), about 2.5% to about 20% (by weight), about 2.5% to about 25% (by weight), about 5% to about 10% (by weight), about 5% to about 15% (by weight), about 5% to about 20% (by weight), about 5% to about 25% (by weight), about 10% to about 20%, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 4 0%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 10% to about 65%, about 10% to about 7 0%, about 15% to about 20%, about 15% to about 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45 %, about 15% to about 50%, about 15% to about 55%, about 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30% to about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 40% to about 75%, about 40% to about 80%, about 45% to about 50%, about 45% ~ about 55%, about 45% to about 60%, about 45% to about 65%, about 45% to about 70%, about 45% to about 75%, about 45% to about 80%, about 50% to about 55%, about 50% to about 60%, about 50% to about 65%, about 50% to about 70%, about 50% to about 75%, about 50% to about 80%, about 55% to about 60%, about 55% to about 65%, about 55% to about 70%, about 55% to about 75%, about 55% to about 80%, about 60% to about 65%, about 60% to about 70%, about 60% to about 75%, about 60% to about 80%, about 65% to about 70% (by weight), about 65% to about 75%, about 65% to about 80%.It may comprise, consist essentially of, or consist of one or more digestive aids in an amount of about 70% to about 75%, about 70% to about 80%, or about 75% to about 80%.

[0093] bile acids The pharmaceutical compositions disclosed herein may contain one or more bile acids. The main purpose of the bile acids is to increase the solubility of the fibrates disclosed herein in the glycerolipid mixture, enhance the absorption of the fibrates disclosed herein, thereby improving the pharmacokinetics of the compounds, and / or to improve the availability of the fibrates disclosed herein, promote selected biodistribution, thereby improving the pharmacodynamics of the compounds. Furthermore, as disclosed in Example 2, the bile acids disclosed herein may be used in combination with one or more glycerolipids and / or one or more free C 14-24Improved solubility of the fibrates disclosed herein in fatty acids is achieved by bile acids by preventing recrystallization of the fibrates during solidification when the molar pharmaceutical composition is cooled to room temperature (18-20°C). Improved pharmacokinetic properties are achieved by bile acids through their surfactant properties, breaking down the lipid components of the pharmaceutical compositions disclosed herein into smaller lipid structures that mimic emulsion droplets, thereby facilitating the emulsification process. The "emulsion droplets" mobilize coliapses, creating a larger surface area where pancreatic lipase can digest the hard fatty glycerolipids present therein, ultimately facilitating absorption by absorptive epithelial cells and subsequent chylomicron formation. Bile acids are involved in signaling for the initiation of chylomicron formation. Therefore, inclusion of bile acids in lipid formulations maximizes this signaling pathway and chylomicron production, and the resulting improved pharmacodynamic properties provided by bile acids result from increasing the availability of fibrates by increasing their content within chylomicrons before they enter the circulation, and subsequently facilitating their delivery to compartments such as the brain across membranes such as the blood-brain barrier and the choroid plexus.

[0094] Bile acids, amphiphilic molecules with an HLB greater than 12, possess a unique chemical structure distinct from typical aliphatic surfactants due to the presence of a large, rigid, flat, hydrophobic portion of a steroid nucleus bearing two to four hydroxyl groups. Specifically, bile acids contain the following basic components: (1) four rings, (2) a 5- or 8-carbon side chain terminating in a carboxylic acid, and (3) several hydroxyl groups (their position / number varies among various salts). The rings are assigned letters A, B, C, and D based on their distance from the side chain bearing the -COOH group, with the D ring being the furthest away (and 1 C smaller than the other rings), as explained below. The β-hydroxyl group points up / out, the α-group points down, and all bile acids possess a 3-hydroxyl group derived from their cholesterol precursor. The chemical structure of bile salts makes this emulsification route useful according to the teachings of the present disclosure, and therefore synthetic surfactants do not work.

[0095] Examples of bile acids include, but are not limited to, chenodeoxycholic acid, cholic acid, dafachronic acid, deoxycholic acid, glycocholic acid, glycohenodeoxycholic acid, lithocholic acid, taurochenodeoxycholic acid, taurocholic acid, and any stereoisomers thereof. Cholic acid and chenodeoxycholic acid are called primary bile acids, while deoxycholic acid (converted from cholic acid) and lithocholic acid (converted from chenodeoxycholic acid) are called secondary bile acids. Taurocholic acid and glycocholic acid (derivatives of cholic acid) and taurochenodeoxycholic acid and glycochenodeoxycholic acid (derivatives of chenodeoxycholic acid) are the major bile acids that serve as the basis for bile salts found in bile.

[0096] There is a direct correlation between the amount of bile acid present in the pharmaceutical compositions disclosed herein and the improved properties observed. Therefore, the more bile acid present in the pharmaceutical compositions disclosed herein, the greater the improvements in solubility, absorption, and availability of the therapeutic composition. Furthermore, the upper limit of bile acid content in the pharmaceutical compositions disclosed herein is not limited by the bile acid's solubility point. Therefore, the pharmaceutical compositions disclosed herein may contain supersaturating amounts of bile acid. Therefore, the upper limit of bile acid content in the pharmaceutical compositions disclosed herein is its critical micelle concentration (CMC). In addition to the improved properties described above, a further advantage of supersaturating amounts of bile acid is the resulting formation of nanoparticles of crystalline bile acid in the pharmaceutical compositions disclosed herein. Without wishing to be limited by any one theory, bile acid nanoparticles dissolve to form bile salts when exposed to the alkaline environment of the small intestine, which may serve as a reservoir that further facilitates the emulsification process of the pharmaceutical compositions disclosed herein.

[0097] The amount of bile acid useful in the pharmaceutical compositions disclosed herein is less than its CMC.In some embodiments, the amount of bile acid useful in the pharmaceutical compositions disclosed herein is less than its CMC and supersaturated.In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, about 0.1% (by weight), about 0.5% (by weight), about 1.0% (by weight), about 1.0% (by weight), about 1.5% (by weight), about 2.0% (by weight), about 2.5% (by weight), about 3.0% (by weight), about 3.5% (by weight), about 4.0% (by weight), about 4.5% (by weight), about 5.0% (by weight), about It may comprise, consist essentially of, or consist of one or more bile acids in an amount of about 5.5% (by weight), about 6.0% (by weight), about 6.5% (by weight), about 7.0% (by weight), about 7.5% (by weight), about 8.0% (by weight), about 8.5% (by weight), about 9.0% (by weight), about 9.5% (by weight), or about 10.0% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, at least 0.1% (by weight), at least 0.5% (by weight), at least 1.0% (by weight), at least 1.5% (by weight), at least 2.0% (by weight), at least 2.5% (by weight), at least 3.0% (by weight), at least 3.5% (by weight), at least 4.0% (by weight), at least 4.5% (by weight), at least 5.0% (by weight), at least It may comprise, consist essentially of, or consist of one or more bile acids in an amount of 5.5% (by weight), at least 6.0% (by weight), at least 6.5% (by weight), at least 7.0% (by weight), at least 7.5% (by weight), at least 8.0% (by weight), at least 8.5% (by weight), at least 9.0% (by weight), at least 9.5% (by weight), or at least 10.0% (by weight).In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, up to 0.1% (by weight), up to 0.5% (by weight), up to 1.0% (by weight), up to 1.5% (by weight), up to 2.0% (by weight), up to 2.5% (by weight), up to 3.0% (by weight), up to 3.5% (by weight), up to 4.0% (by weight), up to 4.5% (by weight), up to 5.0% (by weight), up to 5.5% (by weight), up to 6.0% (by weight), up to 6.5% (by weight), up to 7.0% (by weight), up to 7.5% (by weight), up to 8.0% (by weight), up to 8.5% (by weight), up to 9.0% (by weight), up to 9.5% (by weight), or up to 10.0% (by weight) of one or more bile acids.

[0098] In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, about 0.1% to about 0.5%, about 0.1% to about 1.0%, about 0.1% to about 2.0%, about 0.1% to about 3.0%, about 0.1% to about 4.0%, about 0.1% to about 5.0%, about 0.1% to about 6.0%, about 0.1% to about 7.0%, about 0.1% to about 8.0%, about 0.1% to about 9.0%, about 0.1% to about 10.0%, about 0.5% to about 1.0%, about 0.5% to about 2.0%, about 0.5% to about 3.0%, about 0.5% to about 4.0%, about 0.5% to about 5.0% , about 0.5% to about 6.0%, about 0.5% to about 7.0%, about 0.5% to about 8.0%, about 0.5% to about 9.0%, about 0.5% to about 10.0%, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%, about 2.0% to about 3.0%, about 2.0% to about 4.0%, about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2.0% to about 7.0%, about 2.0% to about 8.0%, about 2.0% to about 9.0%, about 2.0% to about 10.0%, about 3.0% to about 4.0%, about 3.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%, about 3.0% to about 8.0%, about 3.0% to about 9.0%, about 3.0% to about 10.0%, about 4.0% to about 5.0%, about 4.0% to about 6.0%, about 4.0% to about 7.0%, about 4.0% to about 8.0%, about 4.0% to about 9.0%, about 4.0% to about 10.0%, about 5.0% to about 6.0%, about 5.0% to about 7.0%, It may comprise, consist essentially of, or consist of one or more bile acids in an amount of about 5.0% to about 8.0%, about 5.0% to about 9.0%, about 5.0% to about 10.0%, about 6.0% to about 7.0%, about 6.0% to about 8.0%, about 6.0% to about 9.0%, about 6.0% to about 10.0%, about 7.0% to about 8.0%, about 7.0% to about 9.0%, about 7.0% to about 10.0%, about 8.0% to about 9.0%, about 8.0% to about 10.0%, or about 9.0% to about 10.0% (by weight).

[0099] In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of one or more bile acids at a concentration of, for example, up to 0.01 mM, up to 0.025 mM, up to 0.05 mM, up to 0.075 mM, up to 0.1 mM, up to 0.25 mM, up to 0.5 mM, up to 0.75 mM, up to 1 mM, or up to 5 mM. In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of one or more bile acids at a concentration of, for example, about 0.01 mM to about 0.05 mM, about 0.01 mM to about 0.1 mM, about 0.01 mM to about 0.5 mM, about 0.01 mM to about 1 mM, about 0.01 mM to about 5 mM, about 0.05 mM to about 0.1 mM, about 0.05 mM to about 0.5 mM, about 0.05 mM to about 1 mM, about 0.05 mM to about 5 mM, about 0.1 mM to about 0.5 mM, about 0.1 mM to about 1 mM, about 0.1 mM to about 5 mM, or about 1 mM to about 5 mM.

[0100] C 14-24 fatty acid The pharmaceutical compositions disclosed herein may contain one or more free C 14-24 The free C may include fatty acids. Fatty acids include carboxylic acids with long, unbranched hydrocarbon chains that may be saturated or unsaturated and are hydrophobic molecules with an HLB of less than 4. 14-24 The primary purpose of the fatty acids is to increase the solubility of the fibrates disclosed herein in the glycerolipid mixture and to enhance the absorption of the fibrates disclosed herein, thereby improving the pharmacokinetics of the compounds. The improved solubility properties are due to their ability to be solvents that promote the dissolution of the fibrates disclosed herein, resulting in a reduction in the free C 14-24 The improved absorption properties are achieved by promoting and increasing the formation of micelles by breaking up larger emulsion droplets, thereby mimicking the lipid digestion products of triglycerides, i.e., free fatty acids. 14-24 This is achieved by the fatty acids. 14-24Fatty acids increase the uptake of micelles containing one or more fibrates into absorptive epithelial cells. Furthermore, as disclosed in Example 2, the free C 14-24 Fatty acids improve the solubility of the bile salts disclosed herein.

[0101] In some embodiments, the pharmaceutical compositions disclosed herein comprise an unsaturated free C 14 -C 16 Fatty acids, unsaturated free C 14 -C 18 Fatty acids, unsaturated free C 14 -C 20 Fatty acids, unsaturated free C 14 -C 22 Fatty acids, unsaturated free C 14 -C 24 Fatty acids, unsaturated free C 16 -C 18 Fatty acids, unsaturated free C 16 -C 20 Fatty acids, unsaturated free C 16 -C 22 Fatty acids, unsaturated free C 16 -C 24 Fatty acids, unsaturated free C 18 -C 20 Fatty acids, unsaturated free C 18 -C 22 Fatty acids, unsaturated free C 18 -C 24 Fatty acids, unsaturated free C 20 -C 22 Fatty acids, or unsaturated free C 22 -C 24 one or more free C containing, consisting essentially of, or consisting of fatty acids 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may comprise omega-3 unsaturated free C fatty acids. 18 -C 22 Fatty acids, ω-5 unsaturated free C 18 -C 22 Fatty acids, ω-6 unsaturated free C 18 -C 22 Fatty acids, ω-7 unsaturated free C 18 -C 22 Fatty acids, ω-9 unsaturated free C 18 -C22 Fatty acids, ω-10 unsaturated free C 18 -C 22 Fatty acids, ω-11 unsaturated free C 18 -C 22 Fatty acids, or ω-12 unsaturated free C 18 -C 22 one or more free C containing, consisting essentially of, or consisting of fatty acids 14-24 It may also contain fatty acids.

[0102] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated free C 14 -C 16 Fatty acids, saturated free C 14 -C 18 Fatty acids, saturated free C 14 -C 20 Fatty acids, saturated free C 14 -C 22 Fatty acids, saturated free C 14 -C 24 Fatty acids, saturated free C 16 -C 18 Fatty acids, saturated free C 16 -C 20 Fatty acids, saturated free C 16 -C 22 Fatty acids, saturated free C 16 -C 24 Fatty acids, saturated free C 18 -C 20 Fatty acids, saturated free C 18 -C 22 Fatty acids, saturated free C 18 -C 24 Fatty acids, saturated free C 20 -C 22 Fatty acids, or saturated free C 22 -C 24 one or more free C containing, consisting essentially of, or consisting of fatty acids 14-24 It may also contain fatty acids.

[0103] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated free C 14 -C 16 Mixture of fatty acids, saturated and unsaturated free C 14 -C18 Mixture of fatty acids, saturated and unsaturated free C 14 -C 20 Mixture of fatty acids, saturated and unsaturated free C 14 -C 22 Mixture of fatty acids, saturated and unsaturated free C 14 -C 24 Mixture of fatty acids, saturated and unsaturated free C 16 -C 18 Mixture of fatty acids, saturated and unsaturated free C 16 -C 20 Mixture of fatty acids, saturated and unsaturated free C 16 -C 22 Mixture of fatty acids, saturated and unsaturated free C 16 -C 24 Mixture of fatty acids, saturated and unsaturated free C 18 -C 20 Mixture of fatty acids, saturated and unsaturated free C 18 -C 22 Mixture of fatty acids, saturated and unsaturated free C 18 -C 24 Mixture of fatty acids, saturated and unsaturated free C 20 -C 22 Mixture of fatty acids, or saturated and unsaturated free C 22 -C 24 One or more free C fatty acids comprising, consisting essentially of, or consisting of a mixture of fatty acids 14-24 It may also contain fatty acids.

[0104] free C 14-24Non-limiting examples of fatty acids include palmitic acid (hexadecenoic acid), palmitrinolenic acid, palmitidonic acid, palmitovaccenic acid, palmitoleic acid, sapienic acid, 4-hexadecenoic acid, stearic acid (octadecenoic acid), α-linolenic acid, stearidonic acid, α-eleostearic acid, β-eleostearic acid, pumicic acid, 7,10,13-octadecatrienoic acid, 12-octadecenoic acid, linoleic acid, linoelaidic acid, γ-linolenic acid, calendic acid, pinolenic acid, vaccinic acid, ruminic acid, oleic acid, elaidic acid, petroselinic acid, arachidic acid (eicosanoic acid), dihomo-α-linolenic acid, eicosinic acid, traenoic acid, Acid), eicosapentaenoic acid, 9,12,15-eicosatrienoic acid, β-eicosic acidtraenoic acid, dihomo-linoleic acid, dihomo-γ-linolenic acid, arachidonic acid, paulic acid, 7,10,13-eicosatrienoic acid, gondoic acid, 8,11-eicosadienoic acid, meadic acid, gadoleic acid, 8-eicosenoic acid, behenic acid (docosanoic acid), clupanodonic acid, docosahexaenoic acid, adrenic acid, osbondic acid, erucic acid, lignoceric acid (tetracosanic acid), 9,12,15,18,21-tetracosapentaenoic acid, 6,9,12,15,18,21-tetracosahexaenoic acid, and nervonic acid.

[0105] In some embodiments, the pharmaceutical compositions disclosed herein contain one or more free C in an amount, e.g., about 1% (by weight), about 2.5% (by weight), about 5% (by weight), about 7.5% (by weight), about 10% (by weight), about 12.5% ​​(by weight), about 15% (by weight), about 17.5% (by weight), about 20% (by weight), about 22.5% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 50% (by weight), about 60% (by weight), about 70% (by weight), or about 75% (by weight). 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of one or more free C in an amount of, for example, at least 1% (by weight), at least 2.5% (by weight), at least 5% (by weight), at least 7.5% (by weight), at least 10% (by weight), at least 12.5% ​​(by weight), at least 15% (by weight), at least 17.5% (by weight), at least 20% (by weight), at least 22.5% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 50% (by weight), at least 60% (by weight), at least 70% (by weight), or at least 75% (by weight). 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more free C in an amount of, for example, up to 1% (by weight), up to 2.5% (by weight), up to 5% (by weight), up to 7.5% (by weight), up to 10% (by weight), up to 12.5% ​​(by weight), up to 15% (by weight), up to 17.5% (by weight), up to 20% (by weight), up to 22.5% (by weight), up to 25% (by weight), up to 30% (by weight), up to 35% (by weight), up to 40% (by weight), up to 50% (by weight), up to 60% (by weight), up to 70% (by weight), or up to 75% (by weight). 14-24It may comprise, consist essentially of, or consist of fatty acids.

[0106] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 1% to about 2.5% (by weight), about 1% to about 5% (by weight), about 1% to about 10% (by weight), about 1% to about 15% (by weight), about 1% to about 20% (by weight), about 1% to about 25% (by weight), about 2.5% to about 5% (by weight), about 2.5% to about 10% (by weight), about 2.5% to about 15% (by weight), about 2.5% to about 20% (by weight), about 2.5% to about 25% (by weight), about 2.5% to about 30% (by weight), about 5% to about 10% (by weight), or about 5%. ~15% (by weight), approximately 5% to approximately 20% (by weight), approximately 5% to approximately 25% (by weight), approximately 5% to approximately 30% (by weight), approximately 10% to approximately 15% (by weight), approximately 10% to approximately 20% (by weight), approximately 10% to approximately 25% (by weight), approximately 10% to approximately 30% (by weight), Approximately 10% to approximately 40% (weight basis), approximately 10% to approximately 45% (weight basis), approximately 10% to approximately 50% (weight basis), approximately 10% to approximately 60% (weight basis), approximately 10% to approximately 70% (weight basis), approximately 15% to approximately 20% (weight basis), approximately 15% to approximately 25% (weight basis), approximately 15% to approximately 30% (weight basis), about 15% to about 40% (weight basis), about 15% to about 45% (weight basis), about 15% to about 50% (weight basis), about 15% to about 60% (weight basis), about 15% to about 70% (weight basis), about 20% to about 25% (weight basis), about 20% to about 30% (weight basis), about 2 0% to approx. 40% (weight basis), approx. 20% to approx. 45% (weight basis), approx. 20% to approx. 50% (weight basis), approx. 20% to approx. 60% (weight basis), approx. about 30% to about 70% (by weight), about 30% to about 75% (by weight), about 35% to about 40% (by weight), about 35% to about 50% (by weight), about 35% to about 60% (by weight), about 35% to about 70% (by weight), about 35% to about 75% (by weight), about 40% to about 50% (by weight), about 40% to about 60% (by weight), about 40% to about 70% (by weight), about 40% to about 75% (by weight), about 50% to about 60% (by weight), about 50% to about 70% (by weight), or about 60% to about 70% (by weight) of one or more free C 14-24It may comprise, consist essentially of, or consist of fatty acids.

[0107] In some embodiments, the pharmaceutical compositions disclosed herein contain one or more free C at a concentration of, e.g., at most 0.01 mM, at most 0.025 mM, at most 0.05 mM, at most 0.075 mM, at most 0.1 mM, at most 0.25 mM, at most 0.5 mM, at most 0.75 mM, at most 1 mM, at most 1.25 mM, at most 1.5 mM, at most 1.75 mM, or at most 2 mM. 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acids, e.g., about 0.01 mM to about 0.05 mM, about 0.01 mM to about 0.1 mM, about 0.01 mM to about 0.5 mM, about 0.01 mM to about 1 mM, about 0.01 mM to about 1.25 mM, about 0.01 mM to about 1.5 mM, about 0.01 mM to about 1.75 mM, about 0.01 mM to about 2 mM, about 0.05 mM to about 0.1 mM, about 0.05 mM to about 0.5 mM, about 0.05 mM to about 1 mM, about 0.05 mM to about 1.25 mM, about 0.05 mM to about 1.5 mM, about 0.05 mM to about 2 mM, one or more free C at a concentration of about 1.75 mM, about 0.05 mM to about 2 mM, about 0.1 mM to about 0.5 mM, about 0.1 mM to about 1 mM, about 0.1 mM to about 1.25 mM, about 0.1 mM to about 1.5 mM, about 0.1 mM to about 1.75 mM, about 0.1 mM to about 2 mM, about 0.5 mM to about 1 mM, about 0.5 mM to about 1.25 mM, about 0.5 mM to about 1.5 mM, about 0.5 mM to about 1.75 mM, about 0.5 mM to about 2 mM, about 1 mM to about 1.25 mM, about 1 mM to about 1.5 mM, about 1 mM to about 1.75 mM, or about 15 mM to about 2 mM 14-24 It may comprise, consist essentially of, or consist of fatty acids.

[0108] phospholipids The pharmaceutical compositions disclosed herein may contain one or more phospholipids. Similar to the bile acids disclosed herein, the phospholipids disclosed herein, through their surfactant properties, break down the lipid components of the pharmaceutical compositions disclosed herein into smaller lipid structures that mimic emulsion droplets, thereby facilitating the emulsification process. The "emulsion droplets" mobilize coliapses, creating a larger surface area where pancreatic lipase can digest the hard fatty glycerolipids present there. Furthermore, the phospholipids disclosed herein, along with the free fatty acid surfactants disclosed herein, promote the formation of micelles by associating with lipid digestion products of triglycerides, which then enhances the association of triglyceride digestion products with fatty acid transporters, thereby enhancing the absorption of lipid molecules and associated fibrates into absorptive epithelial cells.

[0109] Phospholipids generally have a hydrophobic tail of one or more fatty acids and a hydrophilic head containing a phosphate functional group, are amphiphilic in nature, and have an HLB greater than 12. Phospholipids include, but are not limited to, phosphoglycerides and sphingophospholipids. Phosphoglycerides have a general structure comprising a glycerol backbone with two fatty acids esterified to the primary and secondary hydroxyl groups of glycerol and a phosphate group esterified to the tertiary hydroxyl group of glycerol. An alcohol group is esterified to the phosphate group of the phosphoglyceride. Phosphoglycerides always contain two fatty acids, usually one saturated and the other unsaturated. Phosphoglycerides are generally classified according to the specific alcohol group present on the phosphoric acid group, such as ethanolamine, choline, serine, or inositol. Non-limiting examples of phosphoglycerides include phosphatidic acid (phosphatidate) (PA), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), cardiolipin, and phosphoinositides, including phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate (PIP2), and phosphatidylinositol triphosphate (PIP3).

[0110] Although structurally different, sphingophospholipids also have a polar head and two non-polar tails.Sphingophospholipids have a general structure that includes a long-chain amino alcohol sphingosine backbone with a fatty acid that forms an amide bond with the amino group of the sphingosine backbone and a phosphate group that is esterified with the hydroxyl group of the sphingosine backbone.Non-limiting examples of sphingophospholipids include ceramide phosphorylethanolamine (Cer-PE), ceramide phosphorylcholine (Cer-PC), and ceramide phosphorylglycerol (Cer-PG).

[0111] In addition to its amphipathic nature, phospholipids can be zwitterionic phospholipids. Zwitterionic phospholipids are fully ionized molecules that contain equal numbers of positively and negatively charged functional groups and are electrically neutral. Non-limiting examples of zwitterionic phospholipids include phosphatidylethanolamine (PE), phosphatidylcholine (PC), ceramide phosphorylethanolamine (Cer-PE), and ceramide phosphorylcholine (Cer-PC).

[0112] The phospholipids disclosed herein include lectins. Lectins are amphiphilic mixtures of glycerophospholipids. In some embodiments, the lectin comprises a mixture of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and phosphatidic acid. In some embodiments, the lectin comprises 19%-21% phosphatidylcholine, 8%-20% phosphatidylethanolamine, 20%-21% phosphatidylinositol, and 5%-11% phospholipids comprising phosphatidylserine and phosphatidic acid.

[0113] In some embodiments, the pharmaceutical compositions disclosed herein may be administered at concentrations of, for example, about 0.1% (by weight), about 0.5% (by weight), about 1.0% (by weight), about 1.0% (by weight), about 1.5% (by weight), about 2.0% (by weight), about 2.5% (by weight), about 3.0% (by weight), about 3.5% (by weight), about 4.0% (by weight), about 4.5% (by weight), about 5.0% (by weight), about It may comprise, consist essentially of, or consist of one or more phospholipids in an amount of 5.5% (by weight), about 6.0% (by weight), about 6.5% (by weight), about 7.0% (by weight), about 7.5% (by weight), about 8.0% (by weight), about 8.5% (by weight), about 9.0% (by weight), about 9.5% (by weight), or about 10.0% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, at least 0.1% (by weight), at least 0.5% (by weight), at least 1.0% (by weight), at least 1.5% (by weight), at least 2.0% (by weight), at least 2.5% (by weight), at least 3.0% (by weight), at least 3.5% (by weight), at least 4.0% (by weight), at least 4.5% (by weight), at least 5.0% (by weight), at least It may comprise, consist essentially of, or consist of one or more phospholipids in an amount of 5.5% (by weight), at least 6.0% (by weight), at least 6.5% (by weight), at least 7.0% (by weight), at least 7.5% (by weight), at least 8.0% (by weight), at least 8.5% (by weight), at least 9.0% (by weight), at least 9.5% (by weight), or at least 10.0% (by weight).In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, up to 0.1% (by weight), up to 0.5% (by weight), up to 1.0% (by weight), up to 1.5% (by weight), up to 2.0% (by weight), up to 2.5% (by weight), up to 3.0% (by weight), up to 3.5% (by weight), up to 4.0% (by weight), up to 4.5% (by weight), up to 5.0% (by weight), up to 5.5% (by weight), by weight), up to 6.0% (by weight), up to 6.5% (by weight), up to 7.0% (by weight), up to 7.5% (by weight), up to 8.0% (by weight), up to 8.5% (by weight), up to 9.0% (by weight), up to 9.5% (by weight), or up to 10.0% (by weight) of one or more phospholipids.

[0114] In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, about 0.1% to about 0.5%, about 0.1% to about 1.0%, about 0.1% to about 2.0%, about 0.1% to about 3.0%, about 0.1% to about 4.0%, about 0.1% to about 5.0%, about 0.1% to about 6.0%, about 0.1% to about 7.0%, about 0.1% to about 8.0%, about 0.1% to about 9.0%, about 0.1% to about 10.0%, about 0.5% to about 1.0%, about 0.5% to about 2.0%, about 0.5% to about 3.0%, about 0.5% to about 4.0%, about 0.5% to about 5.0% , about 0.5% to about 6.0%, about 0.5% to about 7.0%, about 0.5% to about 8.0%, about 0.5% to about 9.0%, about 0.5% to about 10.0%, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%, about 2.0% to about 3.0%, about 2.0% to about 4.0%, about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2.0% to about 7.0%, about 2.0% to about 8.0%, about 2.0% to about 9.0%, about 2.0% to about 10.0%, about 3.0% to about 4.0%, about 3.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%, about 3.0% to about 8.0%, about 3.0% to about 9.0%, about 3.0% to about 10.0%, about 4.0% to about 5.0%, about 4.0% to about 6.0%, about 4.0% to about 7.0%, about 4.0% to about 8.0%, about 4.0% to about 9.0%, about 4.0% to about 10.0%, about 5.0% to about 6.0%, about 5.0% to about 7.0%, It may comprise, consist essentially of, or consist of one or more phospholipids in an amount of about 5.0% to about 8.0%, about 5.0% to about 9.0%, about 5.0% to about 10.0%, about 6.0% to about 7.0%, about 6.0% to about 8.0%, about 6.0% to about 9.0%, about 6.0% to about 10.0%, about 7.0% to about 8.0%, about 7.0% to about 9.0%, about 7.0% to about 10.0%, about 8.0% to about 9.0%, about 8.0% to about 10.0%, or about 9.0% to about 10.0% (by weight).

[0115] C 14-24 fatty acid surfactant The pharmaceutical compositions disclosed herein may contain one or more free C14-24 Fatty acid surfactants may also be included. Fatty acid surfactants contain carboxylic acids with long, unbranched hydrocarbon chains that may be saturated or unsaturated and associated with alkali metals, and are hydrophobic, amphiphilic molecules with an HLB greater than 12. Free C 14-24 The primary purpose of the fatty acid surfactant is to increase the solubility of the fibrates disclosed herein with the glycerolipid mixture and to enhance the absorption of the fibrates disclosed herein, thereby improving the pharmacokinetics of the compounds. The improved solubility properties are due to the increased free C 14-24 The fatty acid surfactants achieve this through the interaction of their carboxylic acid functional groups with the sodium ions present on the fibrates, which neutralize the charge and facilitate compound interaction with the hydrophobic glycolipid mixture. Improved absorption properties are achieved by promoting and increasing the formation of mixed micelles by disrupting larger emulsion droplets, thereby mimicking the lipid digestion products of triglycerides, i.e., free fatty acids, resulting in the release of free C. 14-24 This is achieved by the fatty acid surfactant. 14-24 The fatty acid surfactant increases the uptake of micelles containing one or more fibrates into absorptive epithelial cells. 14-24 The fatty acid surfactants contain free C in combination with alkali metals, such as lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr), or alkaline earth metals, such as beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra). 14-24 It is a fatty acid.

[0116] In some embodiments, the pharmaceutical compositions disclosed herein comprise an unsaturated free C 14 -C 16 Fatty acid surfactant, unsaturated free C 14 -C 18 Fatty acid surfactant, unsaturated free C 14 -C 20 Fatty acid surfactant, unsaturated free C 14 -C22 Fatty acid surfactant, unsaturated free C 14 -C 24 Fatty acid surfactant, unsaturated free C 16 -C 18 Fatty acid surfactant, unsaturated free C 16 -C 20 Fatty acid surfactant, unsaturated free C 16 -C 22 Fatty acid surfactant, unsaturated free C 16 -C 24 Fatty acid surfactant, unsaturated free C 18 -C 20 Fatty acid surfactant, unsaturated free C 18 -C 22 Fatty acid surfactant, unsaturated free C 18 -C 24 Fatty acid surfactant, unsaturated free C 20 -C 22 Fatty acid surfactant, or unsaturated free C 22 -C 24 One or more free Cs comprising, consisting essentially of, or consisting of fatty acid surfactants 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may comprise a fatty acid surfactant. 18 -C 22 Fatty acid surfactant, ω-5 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-6 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-7 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-9 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-10 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-11 unsaturated free C 18 -C 22 Fatty acid surfactant, or ω-12 unsaturated free C 18 -C 22 One or more free Cs comprising, consisting essentially of, or consisting of fatty acid surfactants 14-24 A fatty acid surfactant may be included.

[0117] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated free C 14 -C 16 Fatty acid surfactant, saturated free C 14 -C 18 Fatty acid surfactant, saturated free C 14 -C 20 Fatty acid surfactant, saturated free C 14 -C 22 Fatty acid surfactant, saturated free C 14 -C 24 Fatty acid surfactant, saturated free C 16 -C 18 Fatty acid surfactant, saturated free C 16 -C 20 Fatty acid surfactant, saturated free C 16 -C 22 Fatty acid surfactant, saturated free C 16 -C 24 Fatty acid surfactant, saturated free C 18 -C 20 Fatty acid surfactant, saturated free C 18 -C 22 Fatty acid surfactant, saturated free C 18 -C 24 Fatty acid surfactant, saturated free C 20 -C 22 Fatty acid surfactant, or saturated free C 22 -C 24 One or more free Cs comprising, consisting essentially of, or consisting of fatty acid surfactants 14-24 A fatty acid surfactant may be included.

[0118] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated free C 14 -C 16 Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 18 Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 20 Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 22Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 24 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 18 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 20 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 22 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 24 Mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 20 Mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 22 Mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 24 Mixture of fatty acid surfactants, saturated and unsaturated free C 20 -C 22 Mixture of fatty acid surfactants, or saturated and unsaturated free C 22 -C 24 One or more free C surfactants comprising, consisting essentially of, or consisting of a mixture of fatty acid surfactants 14-24 A fatty acid surfactant may be included.

[0119] free C 14-24Non-limiting examples of fatty acid surfactants include sodium palmitate (hexadecenoate), sodium palmitrinolenate, sodium palmitidonate, sodium palmitovaccenate, sodium palmitoleate, sodium sapienate, sodium 4-hexadecenoate, sodium stearate (octadecenoate), sodium α-linolenate, sodium stearidonate, sodium α-eleostearate, sodium β-eleostearate, sodium pumicate, sodium 7,10,13-octadecatrienoate, sodium 12-octadecenoate, sodium linoleate, sodium linoelaidate, sodium γ-linolenate, sodium calendate, sodium pinolenate, sodium vaccinate, sodium luminate ruminate), sodium oleate, sodium elaidate, sodium petroselinate, sodium arachidic acid (eicosanoic acid), sodium dihomo-α-linolenate, sodium eicosatetraenoate, sodium eicosapentaenoate, sodium 9,12,15-eicosatrienoate, sodium β-eicosatetraenoate, sodium dihomo-linolenate, sodium dihomo-γ-linolenate, sodium arachidonate, sodium paulinate, sodium 7,10,13-eicosatrienoate, sodium gondoate, sodium 8,11-eicosadienoate, sodium meadate, sodium gadoleate, sodium 8-eicosenoate, sodium behenic acid (docosanoic acid), sodium clupanodonate, sodium docosahexaenoate, sodium adrenate, sodium osbondate osbondate, sodium erucate, sodium lignocerate (tetracosanate), sodium 9,12,15,18,21-tetracosapentaenoate, sodium 6,9,12,15,18,21-tetracosahexaenoate, and sodium nervonate.

[0120] One or more free C that may be included in the pharmaceutical compositions disclosed herein 14-24 The lower limit of the fatty acid surfactant is an amount sufficient to solubilize the fibrate and impart its improved absorption characteristics. One or more free C may be included in the pharmaceutical compositions disclosed herein. 14-24 The upper limit for a fatty acid surfactant is its micellar concentration (CMC).

[0121] One or more free C useful in the pharmaceutical compositions disclosed herein 14-24 The amount of fatty acid surfactant is an amount below its CMC. In some embodiments, the pharmaceutical compositions disclosed herein contain one or more free C in an amount of, e.g., about 0.1% (by weight), about 0.5% (by weight), about 1.0% (by weight), about 1.0% (by weight), about 1.5% (by weight), about 2.0% (by weight), about 2.5% (by weight), about 3.0% (by weight), about 3.5% (by weight), about 4.0% (by weight), about 4.5% (by weight), about 5.0% (by weight), about 5.5% (by weight), about 6.0% (by weight), about 6.5% (by weight), about 7.0% (by weight), about 7.5% (by weight), about 8.0% (by weight), about 8.5% (by weight), about 9.0% (by weight), about 9.5% (by weight), or about 10.0% (by weight). 14-24In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acid surfactants. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more free C in an amount of, for example, at least 0.5% (by weight), at least 1.0% (by weight), at least 1.5% (by weight), at least 2.0% (by weight), at least 2.5% (by weight), at least 3.0% (by weight), at least 3.5% (by weight), at least 4.0% (by weight), at least 4.5% (by weight), at least 5.0% (by weight), at least 5.5% (by weight), at least 6.0% (by weight), at least 6.5% (by weight), at least 7.0% (by weight), at least 7.5% (by weight), at least 8.0% (by weight), at least 8.5% (by weight), at least 9.0% (by weight), at least 9.5% (by weight), or at least 10.0% (by weight). 14-24 It may comprise, consist essentially of, or consist of fatty acid surfactants. In some embodiments, the pharmaceutical compositions disclosed herein contain one or more free C in an amount, e.g., at most 0.1% (by weight), at most 0.5% (by weight), at most 1.0% (by weight), at most 1.5% (by weight), at most 2.0% (by weight), at most 2.5% (by weight), at most 3.0% (by weight), at most 3.5% (by weight), at most 4.0% (by weight), at most 4.5% (by weight), at most 5.0% (by weight), at most 5.5% (by weight), at most 6.0% (by weight), at most 6.5% (by weight), at most 7.0% (by weight), at most 7.5% (by weight), at most 8.0% (by weight), at most 8.5% (by weight), at most 9.0% (by weight), at most 9.5% (by weight), or at most 10.0% (by weight). 14-24 It may comprise, consist essentially of, or consist of fatty acid surfactants.

[0122] In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, about 0.1% to about 0.5%, about 0.1% to about 1.0%, about 0.1% to about 2.0%, about 0.1% to about 3.0%, about 0.1% to about 4.0%, about 0.1% to about 5.0%, about 0.1% to about 6.0%, about 0.1% to about 7.0%, about 0.1% to about 8.0%, about 0.1% to about 9.0%, about 0.1% to about 10.0%, about 0.5% to about 1.0%, about 0.5% to about 2.0%, about 0.5% to about 3.0%, or about 0.5% to about 4.0% , about 0.5% to about 5.0%, about 0.5% to about 6.0%, about 0.5% to about 7.0%, about 0.5% to about 8.0%, about 0.5% to about 9.0%, about 0.5% to about 10.0%, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%, about 2.0% to about 3.0%, about 2.0% to about 4.0%, about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2.0% to about 7.0%, about 2.0% to about 8.0%, about 2.0% to about 9.0%, about 2.0% to about 10.0%, about 3.0% to about 4.0%, about 3.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%, about 3.0% to about 8.0%, about 3.0% to about 9.0%, about 3.0% to about 10.0%, about 4.0% to about 5.0%, about 4.0% to about 6.0%, about 4.0% to about 7.0%, about 4.0% to about 8.0%, about 4.0% to about 9.0%, about 4. one or more free C in an amount of 0% to about 10.0%, about 5.0% to about 6.0%, about 5.0% to about 7.0%, about 5.0% to about 8.0%, about 5.0% to about 9.0%, about 5.0% to about 10.0%, about 6.0% to about 7.0%, about 6.0% to about 8.0%, about 6.0% to about 9.0%, about 6.0% to about 10.0%, about 7.0% to about 8.0%, about 7.0% to about 9.0%, about 7.0% to about 10.0%, about 8.0% to about 9.0%, about 8.0% to about 10.0%, or about 9.0% to about 10.0% (by weight) 14-24 It may comprise, consist essentially of, or consist of fatty acid surfactants.

[0123] In some embodiments, the pharmaceutical compositions disclosed herein contain one or more free C, e.g., at a concentration of up to 5 μM, up to 10 μM, up to 15 μM, up to 20 μM, up to 25 μM, up to μM, or up to 35 μM. 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of a fatty acid surfactant, e.g., about 1 μM to about 5 μM, about 1 μM to about 10 μM, about 1 μM to about 15 μM, about 1 μM to about 20 μM, about 1 μM to about 25 μM, about 1 μM to about 30 μM, about 1 μM to about 35 μM, about 5 μM to about 10 μM, about 5 μM to about 15 μM, about 5 μM to about 20 μM, about 5 μM to about 25 μM, about 5 μM to about 30 μM, about 5 μM to about 35 μM, about 10 μM to about 15 μM, μM, approximately 10 μM to approximately 20 μM, approximately 10 μM to approximately 25 μM, approximately 10 μM to approximately 30 μM, approximately 10 μM to approximately 35 μM, approximately 15 μM to approximately 20 μM, approximately 15 μM to approximately 25 μM, approximately 15 μM to approximately 30 μM, approximately 15 μM one or more free C at a concentration of ~about 35 μM, about 20 μM to about 25 μM, about 20 μM to about 30 μM, about 20 μM to about 35 μM, about 25 μM to about 30 μM, about 25 μM to about 35 μM, or about 30 μM to about 35 μM 14-24 It may comprise, consist essentially of, or consist of fatty acid surfactants.

[0124] Curcumin Aspects of the present specification partially disclose curcumin. In some embodiments, the pharmaceutical compositions disclosed herein may contain curcumin. Curcumin is a phenolic pigment extracted from turmeric. Although it is a pharmacologically bioactive molecule, curcumin can promote gallbladder contraction, making this compound useful as a digestive aid disclosed herein. Gallbladder contraction is an important process in fat absorption, and therefore provides an important benefit of increasing the formation of mixed micelles by disrupting larger emulsion droplets, thereby increasing the uptake of micelles containing one or more fibrates into absorptive epithelial cells.

[0125] The amount of curcumin useful in the pharmaceutical compositions disclosed herein is a therapeutically effective amount or an amount effective to promote gallbladder contraction. In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, about 0.1% (by weight), about 0.5% (by weight), about 1.0% (by weight), about 1.0% (by weight), about 1.5% (by weight), about 2.0% (by weight), about 2.5% (by weight), about 3.0% (by weight), about 3.5% (by weight), about 4.0% (by weight), about 4.5% (by weight), about 5.0% (by weight). , about 5.5% (by weight), about 6.0% (by weight), about 6.5% (by weight), about 7.0% (by weight), about 7.5% (by weight), about 8.0% (by weight), about 8.5% (by weight), about 9.0% (by weight), about 9.5% (by weight), or about 10.0% (by weight) of curcumin. In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of curcumin in an amount, e.g., at least 0.1% (by weight), at least 0.5% (by weight), at least 1.0% (by weight), at least 1.5% (by weight), at least 2.0% (by weight), at least 2.5% (by weight), at least 3.0% (by weight), at least 3.5% (by weight), at least 4.0% (by weight), at least 4.5% (by weight), at least 5.0% (by weight), at least 5.5% (by weight), at least 6.0% (by weight), at least 6.5% (by weight), at least 7.0% (by weight), at least 7.5% (by weight), at least 8.0% (by weight), at least 8.5% (by weight), at least 9.0% (by weight), at least 9.5% (by weight), or at least 10.0% (by weight).In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of curcumin in an amount, e.g., up to 0.1% (by weight), up to 0.5% (by weight), up to 1.0% (by weight), up to 1.5% (by weight), up to 2.0% (by weight), up to 2.5% (by weight), up to 3.0% (by weight), up to 3.5% (by weight), up to 4.0% (by weight), up to 4.5% (by weight), up to 5.0% (by weight), up to 5.5% (by weight), up to 6.0% (by weight), up to 6.5% (by weight), up to 7.0% (by weight), up to 7.5% (by weight), up to 8.0% (by weight), up to 8.5% (by weight), up to 9.0% (by weight), up to 9.5% (by weight), or up to 10.0% (by weight).

[0126] In some embodiments, the pharmaceutical compositions disclosed herein may contain, for example, about 0.1% to about 0.5%, about 0.1% to about 1.0%, about 0.1% to about 2.0%, about 0.1% to about 3.0%, about 0.1% to about 4.0%, about 0.1% to about 5.0%, about 0.1% to about 6.0%, about 0.1% to about 7.0%, about 0.1% to about 8.0%, about 0.1% to about 9.0%, about 0.1% to about 10.0%, about 0.5% to about 1.0%, about 0.5% to about 2.0%, about 0.5% to about 3.0%, about 0.5% to about 4.0%, about 0.5% to about 5.0%, %, about 0.5% to about 6.0%, about 0.5% to about 7.0%, about 0.5% to about 8.0%, about 0.5% to about 9.0%, about 0.5% to about 10.0%, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%, about 2.0% to about 3.0%, about 2.0% to about 4.0%, about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2.0 % to about 7.0%, about 2.0% to about 8.0%, about 2.0% to about 9.0%, about 2.0% to about 10.0%, about 3.0% to about 4.0%, about 3.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%, about 3.0% to about 8.0%, about 3.0% to about 9.0%, about 3.0% to about 10.0%, about 4.0% to about 5.0%, about 4.0% to about 6.0%, about 4.0% to about 7.0%, about 4.0% to about 8.0%, about 4.0% to about 9.0%, about 4.0% to about 10.0%, about 5.0% to about 6.0%, about 5.0% to about 7. The composition may comprise, consist essentially of, or consist of curcumin in an amount of about 0%, about 5.0% to about 8.0%, about 5.0% to about 9.0%, about 5.0% to about 10.0%, about 6.0% to about 7.0%, about 6.0% to about 8.0%, about 6.0% to about 9.0%, about 6.0% to about 10.0%, about 7.0% to about 8.0%, about 7.0% to about 9.0%, about 7.0% to about 10.0%, about 8.0% to about 9.0%, about 8.0% to about 10.0%, or about 9.0% to about 10.0% (by weight).

[0127] Glycol Polymer Aspects of the present specification disclose, in part, glycol polymers. In some embodiments, the pharmaceutical compositions disclosed herein may include one or more glycol polymers.

[0128] The pharmaceutical compositions disclosed herein may include a stabilizer in an amount sufficient to stabilize the free acid or free base present in the fibrates disclosed herein. In other aspects of this embodiment, the pharmaceutical compositions disclosed herein may include, for example, less than about 40% (by weight), less than about 35% (by weight), less than about 30% (by weight), less than about 25% (by weight), less than about 20% (by weight), less than about 19% (by weight), less than about 18% (by weight), less than about 17% (by weight), less than about 16% (by weight), less than about 15% (by weight), less than about 14% (by weight). ), less than about 13% (by weight), less than about 12% (by weight), less than about 11% (by weight), less than about 10% (by weight), less than about 9% (by weight), less than about 8% (by weight), less than about 7% (by weight), less than about 6% (by weight), less than about 5% (by weight), less than about 4% (by weight), less than about 3% (by weight), less than about 2% (by weight), or less than about 1% stabilizer.In other aspects of this embodiment, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 1% to about 5% (by weight), about 1% to about 7% (by weight), about 1% to about 10% (by weight), about 1% to about 12% (by weight), about 1% to about 15% (by weight), about 1% to about 18% (by weight), about 1% to about 20% (by weight), about 2% to about 5% (by weight), about 2% to about 7% (by weight), about 2% to about 10% (by weight), about 2% to about 12% (by weight), about 2% to about 15% (by weight), about 2% to about 18% (by weight), about 2% to about 2 0% (by weight), approximately 3% to approximately 5% (by weight), approximately 3% to approximately 7% (by weight), approximately 3% to approximately 10% (by weight), approximately 3% to approximately 12% (by weight), approximately 3% to approximately 15% (by weight), approximately 3% to approximately 18% (by weight), approximately 3% to approximately 20% (by weight), approximately 4% to Approximately 5% (by weight), approximately 4% to approximately 7% (by weight), approximately 4% to approximately 10% (by weight), approximately 4% to approximately 12% (by weight), approximately 4% to approximately 15% (by weight), approximately 4% to approximately 18% (by weight), approximately 4% to approximately 20% (by weight), approximately 5% to approximately 7% (by weight), approximately 5% to approximately Approximately 10% (by weight), approximately 5% to approximately 12% (by weight), approximately 5% to approximately 15% (by weight), approximately 5% to approximately 18% (by weight), approximately 5% to approximately 20% (by weight), approximately 6% to approximately 7% (by weight), approximately 6% to approximately 10% (by weight), approximately 6% to approximately 12% (by weight), approximately 6% to about 15% (by weight), about 6% to about 18% (by weight), about 6% to about 20% (by weight), about 7% to about 10% (by weight), about 7% to about 12% (by weight), about 7% to about 15% (by weight), about 7% to about 18% (by weight), about 7% to about 20% (by weight) ), about 8% to about 10% (by weight), about 8% to about 12% (by weight), about 8% to about 15% (by weight), about 8% to about 18% (by weight), about 8% to about 20% (by weight), about 9% to about 10% (by weight), about 9% to about 12% (by weight), about 9% to about 15% (by weight), about 9% to about 18% (by weight), about 9% to about 20% (by weight), about 10% to about 12% (by weight), about 10% to about 15% (by weight), about 10% to about 18% (by weight), or about 10% to about 20% (by weight).

[0129] The stabilizers disclosed herein are not solvents because they are used in amounts that do not result in substantial dissolution of the solute. Thus, the amount of stabilizer used in the solid solution compositions disclosed herein results in dissolution of 85% or less of the fibrate disclosed herein. In aspects of this embodiment, the amount of stabilizer used in the solid solution compositions disclosed herein results in dissolution of, for example, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, or 5% or less of the fibrate disclosed herein.

[0130] In one embodiment, the glycol polymer may comprise a pharmaceutically acceptable PEG polymer. PEG polymers, also known as polyethylene oxide (PEO) or polyoxyethylene (POE) polymers, are prepared by polymerization of ethylene oxide and are commercially available over a wide range of molecular weights, from 100 g / mol to 10,000,000 g / mol. Low-molecular-weight PEG polymers are liquids or low-melting-point solids, while high-molecular-weight PEG polymers are solids. In one aspect of this embodiment, the PEG polymer used as a stabilizer is a liquid PEG polymer. In this aspect of the embodiment, the PEG polymer has a molecular weight of, for example, 100 g / mol or less, 200 g / mol or less, 300 g / mol or less, 400 g / mol or less, 500 g / mol or less, 600 g / mol or less, 700 g / mol or less, 800 g / mol or less, 900 g / mol or less, or 1000 g / mol or less.

[0131] PEG polymers include PEG100, PEG200, PEG300, PEG400, PEG500, PEG600, PEG700, PEG800, PEG900, PEG1000, PEG1100, PEG1200, PEG1300, PEG1400, PEG1500, PEG1600, PEG1700, PEG1800, PEG1900, PEG2000, PEG2100, PEG2200, PEG2300, PEG2400, PEG2500, PEG2600, PEG2700, PEG2800, PEG2900, PEG3000, PEG3250, PEG3350, Examples of suitable PEG-10,110,120,130,140,150,160,170,180,190,190,190,100,110,120,130,140,150,160,170,18 ...

[0132] In another embodiment, the glycol polymer may comprise a pharmaceutically acceptable polypropylene glycol (PPG) polymer. Also known as polypropylene oxide (PPO) or polyoxypropylene (POP) polymers, PPG polymers are prepared by polymerization of propylene oxide and are commercially available over a wide range of molecular weights, from 100 g / mol to 10,000,000 g / mol. Low-molecular-weight PPG polymers are liquids or low-melting-point solids, while high-molecular-weight PPG polymers are solids. In one aspect of this embodiment, the PPG polymer used as a stabilizer is a liquid PPG polymer. In this aspect of this embodiment, the PPG polymer has a molecular weight of, for example, 100 g / mol or less, 200 g / mol or less, 300 g / mol or less, 400 g / mol or less, 500 g / mol or less, 600 g / mol or less, 700 g / mol or less, 800 g / mol or less, 900 g / mol or less, or 1000 g / mol or less.

[0133] PPG polymers include PPG100, PPG200, PPG300, PPG400, PPG500, PPG600, PPG700, PPG800, PPG900, PPG1000, PPG1100, PPG1200, PPG1300, PPG1400, PPG1500, PPG1600, PPG1700, PPG1800, PPG1900, PPG2000, PPG2100, PPG2200, PPG2300, PPG2400, PPG2500, PPG2600, PPG2700, PPG2800, PPG2900, PPG3000, PPG3250, PPG3350, These include, but are not limited to, PPG3500, PPG3750, PPG4000, PPG4250, PPG4500, PPG4750, PPG5000, PPG5500, PPG6000, PPG6500, PPG7000, PPG7500, PPG8000, PPG8500, PPG9000, PPG9500, PPG10,000, PPG11,000, PPG12,000, PPG13,000, PPG14,000, PPG15,000, PPG16,000, PPG17,000, PPG18,000, PPG19,000, or PPG20,000.

[0134] In some embodiments, the pharmaceutical compositions disclosed herein do not comprise a glycol polymer. In aspects of these embodiments, the pharmaceutical compositions disclosed herein do not comprise a PEG polymer. In other aspects of these embodiments, the pharmaceutical compositions disclosed herein do not comprise a PGG polymer. In yet other aspects of these embodiments, the pharmaceutical compositions disclosed herein do not comprise both a PEG polymer and a PGG polymer.

[0135] Emission Effect In one embodiment, a significant amount of the fibrate present in the pharmaceutical compositions disclosed herein is delivered to or enters the lipid digestion and / or absorption pathway. In aspects of this embodiment, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 95% of the fibrate present in the pharmaceutical compositions disclosed herein is delivered to or enters the lipid digestion and / or absorption pathway. In other aspects of this embodiment, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% of the fibrate present in the pharmaceutical compositions disclosed herein is delivered to or enters the lipid digestion and / or absorption pathway. In still other aspects of this embodiment, up to 10%, up to 20%, up to 30%, up to 40%, up to 50%, up to 60%, up to 70%, up to 80%, up to 90%, or up to 95% of the fibrate present in the pharmaceutical compositions disclosed herein is delivered to or enters the lipid digestion and / or absorption pathways.

[0136] In still other aspects of this embodiment, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 90%, about 10% to about 100%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 50%, about 60%, about 65%, about 70%, about 75%, about 80%, about 80%, about 90%, about 95%, about 100%, about 100%, about 25%, about 35%, about 45%, about 50%, about 5 ... 0% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 20% to about 100%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, Approximately 30% to approximately 100%, approximately 40% to approximately 50%, approximately 40% to approximately 60%, approximately 40% to approximately 70%, approximately 40% to approximately 80%, approximately 40% to approximately 90%, approximately 40% to approximately 100%, approximately 50% to approximately 60%, approximately 50% to approximately 70%, approximately 50% to approximately 80%, approximately 50% to approximately 90%, approximately 50% to approximately 100%, approximately 60% to approximately 70%, approximately 60% to approximately 80%, about 60% to about 90%, about 60% to about 100%, about 70% to about 80%, about 70% to about 90%, about 70% to about 100%, about 80% to about 90%, about 80% to about 100%, or about 90% to about 100% is delivered to or enters the lipid digestion and / or absorption pathways.

[0137] In one embodiment, a small amount of fibrate present in the pharmaceutical compositions disclosed herein is absorbed by the capillaries and enters the blood directly. In aspects of this embodiment, up to 1%, up to 5%, up to 10%, up to 20%, up to 30%, up to 40%, up to 50%, up to 60%, up to 70%, up to 80%, up to 90%, or up to 95% of the fibrate present in the pharmaceutical compositions disclosed herein is absorbed by the capillaries and enters the blood directly. In aspects of this embodiment, about 1% to about 10%, about 1% to about 20%, about 1% to about 30%, about 1% to about 40%, about 1% to about 50%, about 1% to about 60%, about 1% to about 70%, about 1% to about 80%, about 1% to about 90%, about 1% to about 95%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 90%, about 10% to about 95%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 20% to about 95%, about 3 0% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, about 30% to about 95%, about 40% to about 50%, about 40% to about 60%, about 40% to about 70%, about 40% to about 80%, about 40% to about 90%, about 40% to about 95%, about 50% to about 60%, about 50% to about 70%, about 50 % to about 80%, about 50% to about 90%, about 50% to about 95%, about 60% to about 70%, about 60% to about 80%, about 60% to about 90%, about 60% to about 95%, about 70% to about 80%, about 70% to about 90%, about 70% to about 95%, about 80% to about 90%, about 80% to about 95%, or about 90% to about 95% is absorbed by the capillaries and enters the blood directly.

[0138] Formulation Procedure The inclusion of one or more digestive enhancers in one or more fibrates in the pharmaceutical composition disclosed herein is applicable to any fibrate that is administered by a route of administration (such as oral delivery) where the compound is absorbed through the gastrointestinal tract.However, the formulation of the pharmaceutical composition disclosed herein depends on the solubility of the fibrate in one or more glycerolipids used to formulate the pharmaceutical composition.Therefore, the formulation of any particular fibrate disclosed herein is achieved by the process described below, which produces a pharmaceutical composition in which one or more fibrates remain stably incorporated in the glycerolipid mixture.

[0139] In some embodiments, the selected fibrate may be formulated using 1) a glycerolipid, including at least one liquid fat (a glycerolipid that is liquid at 18°C) and at least one hard fat (a glycerolipid that is solid at 18°C), and 2) one or more digestive enhancers. In some embodiments, one or more liquid and hard fats are first heated, and one or more digestive enhancers are solubilized in the glycerolipid mixture. Once the dissolution of the digestive enhancer is complete, and if appropriate, the temperature of the mixture can be adjusted, and then the selected fibrate is dissolved in the heated mixture to incorporate the compound. In some embodiments, one or more liquid fats are first heated, and one or more digestive enhancers are solubilized in the liquid fat. Once the dissolution of the digestive enhancer is complete, and if appropriate, the temperature of the mixture can be adjusted, and then the selected fibrate is dissolved in the heated mixture to incorporate the compound. Once the fibrate is completely dissolved, one or more hard fats are then added to the heated mixture. In some embodiments, one or more digestive enhancers are first heated, and then the selected fibrate is dissolved in the heated mixture to incorporate the compound. Once dissolution of the fibrate is complete, and if appropriate, the temperature of the mixture can be adjusted, one or more liquid fats are then added and incorporated into the mixture. Once dissolution of the one or more liquid fats is complete, one or more hard fats are then added and incorporated into the mixture. The initial heating step in all procedures is performed at a temperature sufficient to dissolve the one or more digestive enhancers and the selected fibrates, which can be empirically determined based on the melting points of the selected ingredients. Generally, this temperature range is from about 60°C to about 170°C. Any subsequent adjustments to the heat when one or more liquid fats and / or one or more hart fats are added to the mixture are performed at a temperature sufficient to melt the hard fats, which can be empirically determined based on the melting points of the hard fats used in the formulation. Generally, this temperature range is from about 40°C to about 60°C.

[0140] The incorporated mixture is then allowed to cool to room temperature, at which point stirring is stopped and the mixture is transferred to a suitable container and allowed to solidify. Once cooled, the pharmaceutical composition can optionally be stability tested by reheating the composition to a temperature sufficient to melt the composition. The reheating step is carried out at a temperature sufficient to melt the glycerolipid component, which can be empirically determined based on the melting point of the hard fat used in the formulation. Generally, this temperature range is 40°C to 50°C. The selection of one or more digestive enhancers is generally not a critical component in this process, as bile acids, free fatty acids, phospholipids, or free fatty acid surfactants can all be used in any combination to achieve the pharmaceutical compositions disclosed herein. As shown in Example 2, all preparation methods involve a complete melt phase, which upon cooling, results in nanocrystallization of some components, as evidenced in XRPD spectra.

[0141] Example 3 illustrates the fibrate formulated according to this process. These examples also reveal two formulation subgroups. In one subgroup, the presence of one or more digestive enhancers does not appreciably increase the solubility of the fibrate in the glycerolipid matrix. Instead, the presence of the digestive enhancer helps to improve the bioavailability of the fibrate.

[0142] Methods and Uses Aspects of the present specification, in part, disclose a method of treating an individual with chronic inflammation. In one embodiment, the method comprises administering a pharmaceutical composition disclosed herein to an individual in need thereof, whereby the administration reduces symptoms associated with chronic inflammation, thereby treating the individual. Another aspect of the present specification, in part, discloses a method of treating an individual with neuroinflammation. In one embodiment, the method comprises administering a pharmaceutical composition disclosed herein to an individual in need thereof, whereby the administration reduces symptoms associated with neuroinflammation, thereby treating the individual.

[0143] Aspects of the present specification, in part, disclose pharmaceutical compositions as disclosed herein for use in treating chronic inflammation. Other aspects of the present specification, in part, disclose pharmaceutical compositions as disclosed herein for use in treating neuroinflammation.

[0144] Aspects of the present specification disclose, in part, the use of the pharmaceutical compositions disclosed herein to treat chronic inflammation. Other aspects of the present specification disclose, in part, the use of the pharmaceutical compositions disclosed herein to treat neuroinflammation.

[0145] Since the pharmaceutical compositions disclosed herein rely on the digestive processes of the gastrointestinal tract, oral administration is the preferred route of administration.

[0146] The present embodiment partially discloses treating an individual suffering from chronic inflammation and / or neuroinflammation.As used herein, the term "treating" refers to reducing or eliminating the clinical symptoms of chronic inflammation and / or neuroinflammation in an individual, or delaying or preventing the onset of the clinical symptoms of chronic inflammation and / or neuroinflammation in an individual.For example, the term "treating" can mean reducing the symptoms of the condition characterized by chronic inflammation and / or neuroinflammation by, for example, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100%. The actual symptoms associated with chronic inflammation and / or neuroinflammation are well known and can be determined by one of skill in the art by considering factors including, but not limited to, the location of the chronic inflammation and / or neuroinflammation, the cause of the chronic inflammation and / or neuroinflammation, the severity of the chronic inflammation, and / or the tissue or organ affected by the chronic inflammation and / or neuroinflammation. Those skilled in the art will know the appropriate symptoms or indicators associated with particular types of chronic inflammation and / or neuroinflammation and will know how to determine whether an individual is a candidate for the treatments disclosed herein.

[0147] Symptoms of chronic inflammation include, but are not limited to, edema, hyperemia, erythema, bruising, tenderness, stiffness, swelling, fever, chills, stuffy nose, headache, respiratory distress, fluid retention, blood clots, loss of appetite, increased heart rate, granuloma formation, fibrous, pus-like, non-viscous serous fluid, or ulcers and pain. The actual symptoms associated with chronic inflammation are well known and can be determined by those skilled in the art by considering factors including, but not limited to, the location of the inflammation, the cause of the inflammation, the severity of the inflammation, the tissue or organ affected, and associated disorders.

[0148] Specific patterns of chronic inflammation are seen during certain situations within the body, such as when inflammation occurs at epithelial surfaces or when pyogenic bacteria are involved. For example, granulomatous inflammation is inflammation resulting from the formation of granulomas resulting from a limited but diverse number of diseases (including, but not limited to, tuberculosis, leprosy, sarcoidosis, and syphilis). Suppurative inflammation is inflammation that produces large amounts of pus, consisting of neutrophils, dead cells, and fluid. Infections with pyogenic bacteria, such as Staphylococcus aureus, are characteristic of this type of inflammation. Serous inflammation is inflammation resulting from the abundant exudation of non-viscous serous fluid, generally produced by serous mesothelial cells but which may be derived from plasma. Skin blisters exemplify this inflammatory pattern. Ulcerative inflammation is inflammation resulting from the necrotic loss of tissue from the epithelial surface, exposing the underlying layers and forming ulcers.

[0149] Chronic inflammatory conditions may be associated with a large group of unrelated disorders, underlying a variety of diseases and disorders. The immune system is often involved in chronic inflammatory disorders, as evidenced by both allergic reactions and some myopathies, and many immune system disorders result in abnormal inflammation. Non-immune diseases with etiological origins in chronic inflammatory processes include cancer, atherosclerosis, and ischemic heart disease.Non-limiting examples of disorders that exhibit chronic inflammation as a symptom include acne, acid reflux / heartburn, age-related macular degeneration (AMD), allergies, allergic rhinitis, Alzheimer's disease, amyotrophic lateral sclerosis, anemia, appendicitis, arteritis, arthritis, asthma, atherosclerosis, autoimmune disorders, balanitis, blepharitis, bronchiolitis, bronchitis, bullous pemphigoid, burns, bursitis, cancer, cardiac arrest, carditis, and parsley. Acne disease, cellulitis, cervicitis, cholangitis, cholecystitis, chorioamnionitis, chronic obstructive pulmonary disease (COPD), cirrhosis, colitis, congestive heart failure, conjunctivitis, cyclophosphamide-induced cystitis, cystic fibrosis, cystitis, colds, dacryoadenitis, dementia, dermatitis, dermatomyositis, diabetes, diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic ulcer, digestive system diseases, eczema, emphysema, encephalitis, endocarditis , endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibromyalgia, fibrosis, connective tissue inflammation, gastritis, gastroenteritis, gingivitis, glomerulonephritis, glossitis, heart disease, heart valve dysfunction, hepatitis, hidradenitis suppurativa, Huntington's disease, hyperlipidemic pancreatitis, hypertension, ileitis, infection, inflammatory bowel disease, inflammatory cardiac hypertrophy, insulin resistance, interstitial cystitis, interstitial nephritis, iritis, ischemia, ischemic heart disease, keratitis, Keratoconjunctivitis, laryngitis, lupus nephritis, mastitis, mastoiditis, meningitis, metabolic syndrome (syndrome X), migraine, multiple sclerosis, myelitis, myocarditis, myositis, nephritis, non-alcoholic steatohepatitis, obesity, omphalitis, oophoritis, orchitis, osteochondritis, osteopenia, osteomyelitis, osteoporosis, osteitis, otitis, pancreatitis, Parkinson's disease, parotitis, pelvic inflammatory disease, pemphigus vulgaris vularis), pericarditis, peripheral neuropathy, peritonitis, pharyngitis, phlebitis, pleuritis, pneumonitis, polycystic nephritis, proctitis, prostatitis, psoriasis, pulpitis, pyelonephritis, portal phlebitis, renal failure, reperfusion injury, retinitis, rheumatic fever, rhinitis, salpingitis, sarcoidosis, sialadenitis, sinusitis, spastic colon, stenosis, stomatitis, stroke, surgical complications, synovitis, tendinitis, tendinosis, tenosynovitis, thrombophlebitis, tonsillitis, trauma, traumatic brain injury, transplant rejection, trigonitis, tuberculosis, tumor, urethritis, ursitis, uveitis, vaginitis, vasculitis, and vulvitis.See also, Eric R. First, Application of Botulinum Toxin to the Management of Neurogenic Inflammatory Disorders, U.S. Patent No. 6,063,768, which is incorporated herein by reference in its entirety.

[0150] In one embodiment, chronic inflammation includes tissue inflammation. Tissue inflammation is chronic inflammation limited to a specific tissue or organ. In aspects of this embodiment, tissue inflammation includes, for example, skin inflammation, muscle inflammation, tendon inflammation, ligament inflammation, bone inflammation, cartilage inflammation, lung inflammation, heart inflammation, liver inflammation, pancreas inflammation, kidney inflammation, bladder inflammation, stomach inflammation, intestinal inflammation, neuroinflammation, and brain inflammation.

[0151] In another embodiment, chronic inflammation includes systemic inflammation. The process involved is the same as tissue inflammation, but systemic inflammation is not limited to specific tissues, but actually overwhelms the body, involving endothelium and other organ systems. When caused by infectious diseases, the term sepsis is used, and the term bacteremia is particularly used for bacterial sepsis and viremia, especially viral sepsis. Vasodilation and organ dysfunction are serious problems associated with a wide range of infectious diseases, which can lead to septic shock and death.

[0152] In another embodiment, chronic inflammation includes arthritis.Arthritis includes a group of conditions involving damage to the body's joints due to inflammation of the synovial membrane, including, but not limited to, osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthropathies such as ankylosing spondylitis, reactive arthritis (Reiter's syndrome), psoriatic arthritis, enteropathic arthritis associated with inflammatory bowel disease, Whipple's disease and Behcet's disease, septic arthritis, gout (also known as gouty arthritis, crystalline synovitis, and metabolic arthritis), pseudogout (calcium pyrophosphate deposition disease), and Still's disease.Arthritis can affect a single joint (monoarthritis), two to four joints (oligoarthritis), or five or more joints (polyarthritis), and can be either an autoimmune disease or a non-autoimmune disease.

[0153] In another embodiment, chronic inflammation includes autoimmune disorders. Autoimmune diseases can be broadly divided into systemic and organ-specific autoimmune disorders according to the main clinicopathological features of each disease. Systemic autoimmune diseases include, but are not limited to, systemic lupus erythematosus (SLE), Sjogren's syndrome, scleroderma, rheumatoid arthritis, and polymyositis. Localized autoimmune diseases can be endocrinological (such as type 1 diabetes, Hashimoto's thyroiditis, Addison's disease), dermatological (pemphigus vulgaris), hematological (autoimmune hemolytic anemia), neurological (multiple sclerosis), or can involve a well-defined mass in virtually any body tissue. Types of autoimmune disorders include acute disseminated encephalomyelitis (ADEM), Addison's disease, allergies or hypersensitivity disorders, amyotrophic lateral sclerosis, antiphospholipid syndrome (APS), arthritis, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease, autoimmune pancreatitis, bullous pemphigoid, celiac disease, Chagas disease, chronic obstructive pulmonary disease (COPD), type 1 diabetes mellitus (IDDM), endometriosis, fibromyalgia, Goodpasture's syndrome, Graves' disease, Guillain-Barré syndrome (GBS), Hashimoto's thyroiditis, hidradenitis suppurativa, idiopathic thrombocytopenic purpura, and These include, but are not limited to, inflammatory bowel disease, interstitial cystitis, lupus (including discoid lupus erythematosus, drug-induced lupus nephritis, neonatal lupus, subacute cutaneous lupus erythematosus, and systemic lupus erythematosus), morphea, multiple sclerosis (MS), myasthenia gravis, myopathy, narcolepsy, neuromyotonia, pemphigus vulgaris, pernicious anemia, primary biliary cirrhosis, relapsing disseminated encephalomyelitis (multiphasic disseminated encephalomyelitis), rheumatic fever, schizophrenia, scleroderma, Sjögren's syndrome, tenosynovitis, vasculitis, and vitiligo. See Pamela D. Van Schaack & Kenneth L. Tong, "Treatment of Autoimmune Disorder with a Neurotoxin," U.S. Patent Application Publication No. 2006 / 138059, incorporated herein by reference in its entirety.

[0154] In another embodiment, the chronic inflammation includes myopathy. Myopathy occurs when the immune system inappropriately attacks muscle components, leading to muscle inflammation. Myopathy includes inflammatory myopathy and autoimmune myopathy. Myopathy includes, but is not limited to, dermatomyositis, inclusion body myositis, and polymyositis.

[0155] In another embodiment, chronic inflammation comprises vasculitis. Vasculitis is a group of disorders characterized by inflammation of blood vessel walls, including lymphatic vessels and blood vessels such as veins (phlebitis), arteries (arteritis) and capillaries, due to leukocyte migration and resulting damage. Inflammation can affect blood vessels of any size anywhere in the body. It can affect either arteries and / or veins. Inflammation can be localized, meaning it affects a single location within blood vessels, or it can be widespread, with areas of inflammation scattered throughout a specific organ or tissue, or even affecting two or more organ systems in the body. Vasculitides include, but are not limited to, Buerger's disease (thromboangiitis obliterans), cerebral vasculitis (central nervous system vasculitis), Churg-Strauss arteritis, cryoglobulinemia, essential cryoglobulinemic vasculitis, giant cell (temporal) arteritis, golfer's vasculitis, Henoch-Schönlein purpura, hypersensitivity vasculitis (allergic vasculitis), Kawasaki disease, microscopic polyarteritis / polyangiitis, polyarteritis nodosa, polymyalgia rheumatica (PMR), rheumatoid vasculitis, Takayasu's arteritis, Wegener's granulomatosis, and vasculitis secondary to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), relapsing polychondritis, connective tissue disorders such as Behçet's disease, or other connective tissue disorders, or vasculitis secondary to viral infections.

[0156] In another embodiment, the chronic inflammation comprises a skin disorder, including, but not limited to, acne, including acne vulgaris, bullous pemphigoid, dermatitis, including atopic dermatitis and chronic photosensitive dermatitis, eczema, such as atopic eczema, contact eczema, dry eczema, seborrheic dermatitis, dyshidrosis, nummular eczema, venous eczema, dermatitis herpetiformis, neurodermatitis, and autosensitization dermatitis, as well as psoriasis, including statis dermatitis, hidradenitis suppurativa, lichen planus, plaque psoriasis, nail psoriasis, guttate psoriasis, scalp psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, and psoriatic arthritis, rosacea, and scleroderma, including morphea.

[0157] In another embodiment, the chronic inflammation comprises a gastrointestinal disorder, including, but not limited to, irritable bowel disease, inflammatory bowel disease including Crohn's disease, and ulcerative colitis, such as ulcerative proctitis, left-sided colitis, pancolitis, and fulminant colitis.

[0158] In another embodiment, chronic inflammation includes cardiovascular disease. When LDL cholesterol is embedded in the arterial wall, it can trigger an immune response. Chronic inflammation can eventually damage arteries, which can lead to arterial rupture. Cardiovascular disease is any of several specific diseases that affect the heart itself and / or the vascular system, particularly the veins and arteries that enter and exit the heart. There are more than 60 types of cardiovascular disorders, including but not limited to: hypertension, endocarditis, myocarditis, heart valve dysfunction, congestive heart failure, myocardial infarction, diabetic heart condition, vascular inflammation such as arteritis, phlebitis, and vasculitis; arterial occlusive diseases such as arteriosclerosis and stenosis, inflammatory cardiac hypertrophy, peripheral arterial disease; aneurysm; embolism; dissection; pseudoaneurysm; vascular malformation; vascular nevi; thrombosis; thrombophlebitis; varicose veins; and stroke. Symptoms of cardiovascular disorders affecting the heart include, but are not limited to, chest pain or discomfort (angina), pain in one or both arms, left shoulder, neck, jaw, or back, shortness of breath, dizziness, rapid heartbeat, nausea, abnormal heartbeat, and fatigue. Symptoms of cardiovascular disorders affecting the brain include, but are not limited to, sudden numbness or weakness of the face, arms, or legs, especially on one side of the body; sudden confusion or difficulty speaking or understanding speech; sudden difficulty seeing in one or both eyes; sudden dizziness, difficulty walking, or loss of balance or coordination; and sudden severe headache of unknown cause. Symptoms of cardiovascular disorders affecting the legs, pelvis, and / or arms include, but are not limited to, claudication (muscle pain, soreness, or cramps) and cold or numb feet or toes, especially at night.

[0159] In another embodiment, the chronic inflammation includes cancer. Inflammation regulates the microenvironment surrounding tumors and contributes to their proliferation, survival, and migration. For example, fibrinous inflammation results from a significant increase in vascular permeability, allowing fibrin to pass through blood vessels. In the presence of appropriate procoagulant stimuli, such as cancer cells, fibrous exudates are deposited. This is generally found in serous cavities, and the fibrous exudates can transform into scars between the serosa, limiting the function of the serosa. In another example, the cancer is an inflammatory cancer, such as an NF-κB-driven inflammatory cancer.

[0160] In another embodiment, chronic inflammation includes pharmacologically induced inflammation.Certain drugs or exogenous chemical compounds are known to affect inflammation.For example, vitamin A deficiency causes an increase in inflammatory response.Certain illegal drugs, such as cocaine and ecstasy, may exert some of their harmful effects by activating transcription factors (e.g., NF-κB) closely related to inflammation.

[0161] In another embodiment, chronic inflammation includes infectious diseases. Infectious organisms can escape from the immediate tissue through the circulatory system or lymphatic system, where they can spread to other parts of the body. If the organism is not contained by the effects of acute inflammation, it may access the lymphatic system through nearby lymphatic vessels. Infection of the lymphatic vessels is known as lymphangitis, and infection of the lymph nodes is known as lymphadenitis. Pathogens can access the bloodstream through lymphatic drainage to the circulatory system. Infectious diseases include, but are not limited to, bacterial cystitis, bacterial encephalitis, pandemic influenza, viral encephalitis, and viral hepatitis (A, B, and C).

[0162] In another embodiment, the chronic inflammation comprises tissue or organ damage, including but not limited to burns, lacerations, wounds, punctures, or trauma.

[0163] In another embodiment, chronic inflammation includes transplant rejection. Transplant rejection occurs when a transplanted organ or tissue is not accepted by the transplant recipient's body because the recipient's immune system attacks the transplanted organ or tissue. Transplant rejection, an adaptive immune response, is mediated through both T cell-mediated and humoral immune (antibody) mechanisms. Transplant rejection can be classified as hyperacute rejection, acute rejection, or chronic rejection. Chronic rejection of a transplanted organ or tissue occurs when rejection is due to poorly understood chronic inflammatory and immune responses against the transplanted tissue. The term "transplant rejection" also includes graft-versus-host disease (GVHD). GVHD is a common complication of allogeneic bone marrow transplantation, in which functional immune cells in the transplanted bone marrow recognize the recipient as "foreign" and launch an immunological attack. It can also occur in blood transfusions under certain circumstances. GVHD is divided into acute and chronic forms. Acute and chronic GVHD involve different immune cell subsets, different cytokine profiles, somewhat different host targets, and appear to respond differently to treatment.

[0164] In another embodiment, chronic inflammation includes Th1-mediated inflammatory diseases. In a well-functioning immune system, the immune response should result in a balanced pro-inflammatory Th1 response and an anti-inflammatory Th2 response appropriate for dealing with immune challenges. Generally speaking, once a pro-inflammatory Th1 response is initiated, the body relies on the anti-inflammatory response triggered by the Th2 response to counteract this Th1 response. This counter-response includes the release of Th2-type cytokines, such as IL-4, IL-5, and IL-13, which are associated with promoting IgE and eosinophil responses in atopy, and IL-10, which also has an anti-inflammatory response. Th1-mediated inflammatory diseases involve excessive pro-inflammatory responses produced by Th1 cells, which cause chronic inflammation. Th1-mediated diseases can be virally, bacterially, or chemically (e.g., environmentally) induced. For example, viruses that cause Th1-mediated diseases can cause chronic or acute infections, which can lead to respiratory disorders or influenza.

[0165] In another embodiment, chronic inflammation includes chronic neurogenic inflammation. Chronic neurogenic inflammation refers to an inflammatory response initiated and / or maintained through the release of inflammatory molecules, such as SP or CGRP, from peripheral sensory nerve endings (i.e., efferent functions of these nerves, as opposed to the normal afferent signaling to the spinal cord). Chronic neurogenic inflammation includes both primary and secondary neurogenic inflammation. As used herein, the term "primary" neurogenic inflammation refers to tissue inflammation (inflammatory symptoms) initiated by or resulting from the release of substances from primary sensory nerve endings (such as C and Aδ fibers). As used herein, the term "secondary" neurogenic inflammation refers to tissue inflammation initiated by non-neuronal sources of inflammatory mediators, such as peptides or cytokines (e.g., extravasation from the vascular bed or tissue interstitium, such as mast cells or immune cells), which stimulate sensory nerve endings and cause the release of inflammatory mediators from nerves. The net effect of both forms of chronic neurogenic inflammation (primary and secondary) is an inflammatory state maintained by sensitization of peripheral sensory nerve fibers. The resulting physiological consequences of chronic neurogenic inflammation depend on the tissue in question and can include, for example, cutaneous pain (allodynia, hyperalgesia), joint pain and / or arthritis, visceral pain and dysfunction, pulmonary dysfunction (asthma, COPD), and bladder dysfunction (pain, overactive bladder).

[0166] Neuroinflammation includes both acute and chronic neuroinflammation. Acute neuroinflammation typically occurs immediately after central nervous system injury and is characterized by rapid microglial activation, release of inflammatory molecules, endothelial cell activation, platelet deposition, and tissue edema. Chronic neuroinflammation is characterized by persistent activation of glial cells and recruitment of other immune cells to the brain. However, over time, chronic inflammation leads to the degradation of tissues and the BBB and the generation of reactive oxygen species. The inflammatory signals released by microglia recruit peripheral immune cells to help initiate a neuroimmune response.

[0167] Chronic inflammation is typically associated with neurodegenerative diseases. Neurodegenerative diseases are caused by the progressive loss of neuronal structure or function in a process known as neurodegeneration. Such neuronal damage may ultimately result in cell death. Neurodegeneration can occur in the brain at many different levels of neural circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered incurable. Two major contributing factors to neurodegeneration are oxidative stress and neuroinflammation. Non-limiting examples of neurodegenerative diseases associated with neuroinflammation include Alzheimer's disease, amyotrophic lateral sclerosis, aneurysms, anxiety, aphasia, Asperger's syndrome, ataxia, attention deficit hyperactivity disorder, bipolar disorder, brain cancer, cancer-related or chemotherapy-related cognitive impairment, cerebral ischemia, cerebral palsy, chronic fatigue syndrome, CNS neuropathy, Creutzfeldt-Jakob disease, dementia, depression, encephalitis, epilepsy, fibromyalgia, functional neurological disorders, Guillain-Barré syndrome, headache, idiopathic intracranial hypertension, migraine, multiple sclerosis, Parkinson's disease, pediatric neuroinflammatory disorders, perioperative neurocognitive impairment, postoperative cognitive decline, post-traumatic stress disorder, SARS-CoV-2 infection, schizophrenia, stroke, substance abuse-related neuroinflammation, traumatic brain injury, and Tourette's syndrome.

[0168] The composition or compound is administered to an individual.The individual is typically human.Typically, any individual who is a candidate for conventional chronic inflammation and / or neuroinflammation treatment is also a candidate for the chronic inflammation and / or neuroinflammation treatment disclosed herein.Preoperative assessment typically includes a thorough informed consent that discloses all the relevant risks and benefits of the procedure, as well as a routine medical history and physical examination, including biomarker evaluation.

[0169] The pharmaceutical compositions disclosed herein may contain a therapeutically effective amount of a fibrate. As used herein, the term "effective amount" is synonymous with "therapeutically effective amount," "effective dose," or "therapeutically effective dose," and when used in relation to the treatment of chronic inflammation and / or neuroinflammation, refers to the minimum dose of a fibrate disclosed herein required to achieve the desired therapeutic effect, including a dose sufficient to alleviate symptoms associated with chronic inflammation and / or neuroinflammation. The effectiveness of a fibrate disclosed herein in treating chronic inflammation and / or neuroinflammation can be determined by observing an individual's improvement based on one or more clinical symptoms and / or physiological indicators related to the condition. Improvement in chronic inflammation and / or neuroinflammation can also be indicated by a reduced need for concomitant therapy.

[0170] The appropriate effective amount of the fibrates disclosed herein to be administered to an individual for a particular chronic inflammation and / or neuroinflammation can be determined by one skilled in the art by considering factors including, but not limited to, the type of chronic inflammation and / or neuroinflammation, the location of the chronic inflammation and / or neuroinflammation, the cause of the chronic inflammation and / or neuroinflammation, the severity of the chronic inflammation and / or neuroinflammation, the desired degree of relief, the desired duration of relief, the specific fibrate used, the pharmacokinetic properties of the specific fibrate used, including release, absorption, distribution, metabolism, and excretion, the mechanism of action, the dose-response relationship, the desired activity, undesirable side effects, the pharmacodynamic properties of the specific fibrate used, including the therapeutic range and duration of action, the nature of other compounds to be included in the composition, the specific formulation, the specific route of administration, the specific characteristics of the patient, such as age, weight, general health, medical history, and risk factors, or any combination thereof. Those skilled in the art will recognize that the effective amount of the fibrates disclosed herein can be extrapolated from in vitro assays and in vivo administration tests using animal models before administration to humans. Furthermore, given the different efficiencies of various administration routes, variations in the required effective amount should be expected. For example, oral administration of the fibrates disclosed herein would generally be expected to require higher dosage levels than intravenous administration. Similarly, systemic administration of the fibrates disclosed herein would be expected to require higher dosage levels than local administration. Variations in these dosage levels can be adjusted using standard empirical routines of optimization well known to those skilled in the art. Those skilled in the art will also recognize that an individual's condition can be monitored throughout the course of the methods or uses disclosed herein, and the effective amount of the fibrates disclosed herein administered can be adjusted accordingly. Therefore, the precise therapeutically effective dosage level and pattern are preferably determined by the responsible healthcare professional, taking into account the factors identified above.

[0171] In some embodiments, a therapeutically effective amount of a fibrate disclosed herein reduces symptoms associated with chronic inflammation and / or neuroinflammation, e.g., by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100%. In other aspects of this embodiment, a therapeutically effective amount of a fibrate disclosed herein reduces symptoms associated with chronic inflammation and / or neuroinflammation by, for example, up to 10%, up to 15%, up to 20%, up to 25%, up to 30%, up to 35%, up to 40%, up to 45%, up to 50%, up to 55%, up to 60%, up to 65%, up to 70%, up to 75%, up to 80%, up to 85%, up to 90%, up to 95%, or up to 100%. In still other aspects of this embodiment, a therapeutically effective amount of a fibrate disclosed herein reduces symptoms associated with chronic inflammation and / or neuroinflammation by, for example, about 10% to about 100%, about 10% to about 90%, about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 20% to about 100%, about 20% to about 90%, about 20% to about 80%, about 20% to about 20%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 30% to about 100%, about 30% to about 90%, about 30% to about 80%, about 30% to about 70%, about 30% to about 60%, or about 30% to about 50%.

[0172] In some embodiments, a therapeutically effective amount of a fibrate disclosed herein generally ranges from about 0.01 mg / kg to about 10 mg / kg. In aspects of these embodiments, an effective amount of a fibrate disclosed herein may be, for example, at least 0.01 mg / kg, at least 0.05 mg / kg, at least 0.1 mg / kg, at least 0.5 mg / kg, at least 1.0 mg / kg, at least 2.0 mg / kg, at least 3.0 mg / kg, at least 4.0 mg / kg, at least 5.0 mg / kg, at least 6.0 mg / kg, at least 7.0 mg / kg, at least 8.0 mg / kg, at least 9.0 mg / kg, or at least 10 mg / kg. In other aspects of these embodiments, an effective amount of a fibrate disclosed herein may be, for example, up to 0.01 mg / kg, up to 0.05 mg / kg, up to 0.1 mg / kg, up to 0.5 mg / kg, up to 1.0 mg / kg, up to 2.0 mg / kg, up to 3.0 mg / kg, up to 4.0 mg / kg, up to 5.0 mg / kg, up to 6.0 mg / kg, up to 7.0 mg / kg, up to 8.0 mg / kg, up to 9.0 mg / kg, or up to 10 mg / kg.In still other aspects of these embodiments, an effective amount of a fibrate disclosed herein may be, for example, about 0.01 mg / kg to about 0.05 mg / kg, about 0.01 mg / kg to about 0.1 mg / kg, about 0.01 mg / kg to about 0.5 mg / kg, about 0.01 mg / kg to about 1.0 mg / kg, about 0.01 mg / kg to about 2.0 mg / kg, about 0.01 mg / kg to about 3.0 mg / kg, about 0.01 mg / kg to about 4.0 mg / kg, about 0.01 mg / kg to about 5.0 mg / kg, about 0.01 mg / kg to about 6.0 mg / kg, or about 0.01 mg / kg to about 1.5 mg / kg. kg, about 0.01mg / kg to about 7.0mg / kg, about 0.01mg / kg to about 8.0mg / kg, about 0.01mg / kg to about 9.0mg / kg, about 0.01mg / kg to about 10mg / kg, about 0.1mg / kg to about 0.5mg / kg, about 0.1mg / kg to about 1.0mg / kg, about 0.1mg / kg to about 2.0mg / kg, about 0.1mg / kg to about 3.0mg / kg, about 0.1mg / kg to about 4.0mg / kg, about 0.1mg / kg to about 5.0mg / kg, about 0.1mg / kg to about 6.0mg / kg, about 0.1mg / kg to about 7.0mg / kg, about 0.1mg / kg to about 8.0mg / kg, about 0.1mg / kg to about 9.0mg / kg, about 0.1mg / kg to about 10mg / kg, about 0.5mg / kg to about 1.0mg / kg, about 0.5mg / kg to about 2.0mg / kg, about 0.5mg / kg to about 3.0mg / kg, about 0.5mg / kg to about 4.0mg / kg, about 0.5mg / kg to about 5.0mg / kg, about 0.5mg / kg to about 6.0mg / kg, about 0.5mg / kg to about 7.0mg / kg, about 0.5mg / kg to about 8.0mg / kg , about 0.5 mg / kg to about 9.0 mg / kg, about 0.5 mg / kg to about 10 mg / kg, about 1.0 mg / kg to about 2.0 mg / kg, about 1.0 mg / kg to about 3.0 mg / kg, about 1.0 mg / kg to about 4.0 mg / kg, about 1.0 mg / kg to about 5.0 mg / kg, about 1.0 mg / kg to about 6.0 mg / kg, about 1.0 mg / kg to about 7.0 mg / kg, about 1.0 mg / kg to about 8.0 mg / kg, about 1.0 mg / kg to about 9.0 mg / kg, or about 1.0 mg / kg to about 10 mg / kg.

[0173] In some embodiments, a therapeutically effective amount of a fibrate disclosed herein generally ranges from about 0.01 mg / kg / day to about 10 mg / kg / day. In aspects of these embodiments, an effective amount of a fibrate disclosed herein may be, for example, at least 0.01 mg / kg / day, at least 0.05 mg / kg / day, at least 0.1 mg / kg / day, at least 0.5 mg / kg / day, at least 1.0 mg / kg / day, at least 2.0 mg / kg / day, at least 3.0 mg / kg / day, at least 4.0 mg / kg / day, at least 5.0 mg / kg / day, at least 6.0 mg / kg / day, at least 7.0 mg / kg / day, at least 8.0 mg / kg / day, at least 9.0 mg / kg / day, or at least 10 mg / kg / day. In other aspects of these embodiments, an effective amount of a fibrate disclosed herein may be, for example, up to 0.01 mg / kg / day, up to 0.05 mg / kg / day, up to 0.1 mg / kg / day, up to 0.5 mg / kg / day, up to 1.0 mg / kg / day, up to 2.0 mg / kg / day, up to 3.0 mg / kg / day, up to 4.0 mg / kg / day, up to 5.0 mg / kg / day, up to 6.0 mg / kg / day, up to 7.0 mg / kg / day, up to 8.0 mg / kg / day, up to 9.0 mg / kg / day, or up to 10 mg / kg / day. In still other aspects of these embodiments, an effective amount of a fibrate disclosed herein may be, for example, from about 0.01 mg / kg / day to about 0.05 mg / kg / day, from about 0.01 mg / kg / day to about 0.1 mg / kg / day, from about 0.01 mg / kg / day to about 0.5 mg / kg / day, from about 0.01 mg / kg / day to about 1.0 mg / kg / day, from about 0.01 mg / kg / day to about 2.0 mg / kg / day, from about 0.01 mg / kg / day to about 3.0 mg / kg / day, from about 0.01 mg / kg / day to about 4.0mg / kg / day, about 0.01mg / kg / day to about 5.0mg / kg / day, about 0.01mg / kg / day to about 6.0mg / kg / day, about 0.01mg / kg / day to about 7.0mg / kg / day, about 0.01mg / kg / day to about 8.0mg / kg / day, about 0.01mg / kg / day to about 9.0mg / kg / day, about 0.01mg / kg / day to about 10mg / kg / day, about 0.1mg / kg / day to about 0.5mg / kg / day, about 0.1mg / kg / day to about 1.0mg / kg / day, about 0.1 mg / kg / day to about 2.0 mg / kg / day, about 0.1 mg / kg / day to about 3.0 mg / kg / day, about 0.1 mg / kg / day to about 4.0 mg / kg / day, about 0.1 mg / kg / day to about 5.0 mg / kg / day, about 0.1 mg / kg / day to about 6.0 mg / kg / day, about 0.1 mg / kg / day to about 7.0 mg / kg / day, about 0.1 mg / kg / day to about 8.0 mg / kg / day, about 0.1 mg / kg / day to about 9.0 mg / kg / day, about 0.1 mg / kg / day to about 10 mg / kg / day, about 0.5 mg / kg / day to about 1.0 mg / kg / day, about 0.5 mg / kg / day to about 2.0 mg / kg / day, about 0.5 mg / kg / day to about 3.0 mg / kg / day, about 0.5 mg / kg / day to about 4.0 mg / kg / day, about 0.5 mg / kg / day to about 5.0 mg / kg / day, about 0.5 mg / kg / day to about 6.0 mg / kg / day kg / day to about 6.0 mg / kg / day, about 0.5 mg / kg / day to about 7.0 mg / kg / day, about 0.5 mg / kg / day to about 8.0 mg / kg / day, about 0.5 mg / kg / day to about 9.0 mg / kg / day, about 0.5 mg / kg / day to about 10 mg / kg / day, about 1.0 mg / kg / day to about 2.0 mg / kg / day, about 1.0 mg / kg / day to about 3.0 mg / kg / day, about 1.0 mg / kg / day to about 4.0 mg / kg / day, about 1.0 mg / kg / day to about 5.0 mg / kg / day, about 1.0 mg / kg / day to about 6.0 mg / kg / day, about 0.5 mg / kg / day to about 7.0 mg / kg / day, about 0.5 mg / kg / day to about 8.0 mg / kg / day, about 0.5 mg / kg / day to about 9.0 mg / kg / day, about 0.5 mg / kg / day to about 10 mg / kg / day, about 1.0 mg / kg / day to about 2.0 mg / kg / day, about 1.0 mg / kg / day to about 3.0 mg / kg / day, about 1.0 mg / kg / day The range may be from about 1.0 mg / kg / day to about 4.0 mg / kg / day, from about 1.0 mg / kg / day to about 5.0 mg / kg / day, from about 1.0 mg / kg / day to about 6.0 mg / kg / day, from about 1.0 mg / kg / day to about 7.0 mg / kg / day, from about 1.0 mg / kg / day to about 8.0 mg / kg / day, from about 1.0 mg / kg / day to about 9.0 mg / kg / day, or from about 1.0 mg / kg / day to about 10 mg / kg / day.

[0174] Administration can be single or cumulative (continuous), and can be easily determined by one skilled in the art. For example, treatment of chronic inflammation and / or neuroinflammation can include a single administration of an effective dose of the pharmaceutical composition disclosed herein. Alternatively, treatment of chronic inflammation and / or neuroinflammation can include multiple administrations of an effective dose of the pharmaceutical composition over a range of time periods, such as once daily, twice daily, three times daily, once every few days, or once weekly. The timing of administration can vary from individual to individual, depending on factors such as the severity of the individual's symptoms. For example, an effective dose of the pharmaceutical composition disclosed herein can be administered to an individual once daily for an indefinite period of time, or until the individual no longer requires treatment. One skilled in the art will recognize that an individual's condition can be monitored throughout the course of treatment and the effective amount of the pharmaceutical composition disclosed herein administered can be adjusted accordingly.

[0175] In one embodiment, a pharmaceutical composition comprising a fibrate disclosed herein, upon administration to an individual, results in a biodistribution of the fibrate that differs from the biodistribution of the fibrate contained in the same pharmaceutical composition, except that it does not contain one or more digestive enhancers disclosed herein.

[0176] In some embodiments, the pharmaceutical composition comprises one or more fibrates, one or more glycerolipids, and one or more digestive enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more digestive enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0177] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 50% to about 95% (by weight) of one or more glycerolipids, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 50% to about 95% (by weight) of one or more glycerolipids, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0178] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 50% to about 95% (by weight) of one or more glycerolipids, and about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 50% to about 95% (by weight) of one or more glycerolipids, and about 0.1% to about 10% (by weight) of one or more digestive enhancers. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0179] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 50% to about 95% (by weight) of one or more glycerolipids, and about 5% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 50% to about 95% (by weight) of one or more glycerolipids, and about 5% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0180] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 50% to about 85% (by weight) of one or more glycerolipids, and about 10% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 50% to about 85% (by weight) of one or more glycerolipids, and about 10% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0181] In some embodiments, the pharmaceutical composition comprises fenofibrate, one or more glycerolipids, and one or more digestive enhancers. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0182] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) fenofibrate, about 50% to about 95% (by weight) one or more glycerolipids, and about 0.1% to about 40% (by weight) one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL fenofibrate, about 50% to about 95% (by weight) one or more glycerolipids, and about 0.1% to about 40% (by weight) one or more digestive enhancers. In some embodiments, the one or more digestive enhancers are one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0183] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) fenofibrate, about 50% to about 95% (by weight) one or more glycerolipids, and about 0.1% to about 10% (by weight) one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL fenofibrate, about 50% to about 95% (by weight) one or more glycerolipids, and about 0.1% to about 10% (by weight) one or more digestive enhancers. In some embodiments, the one or more digestive enhancers are one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0184] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) fenofibrate, about 50% to about 95% (by weight) one or more glycerolipids, and about 5% to about 40% (by weight) one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL fenofibrate, about 50% to about 95% (by weight) one or more glycerolipids, and about 5% to about 40% (by weight) one or more digestive enhancers. In some embodiments, the one or more digestive enhancers are one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0185] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) fenofibrate, about 50% to about 85% (by weight) one or more glycerolipids, and about 10% to about 40% (by weight) one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL fenofibrate, about 50% to about 85% (by weight) one or more glycerolipids, and about 10% to about 40% (by weight) one or more digestive enhancers. In some embodiments, the one or more digestive enhancers are one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0186] In some embodiments, the pharmaceutical composition comprises one or more fibrates, one or more hard fats, one or more liquid fats, and one or more digestive stimulants. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more digestive stimulants comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0187] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 40% to about 50% (by weight) of one or more hard fats, about 30% to about 50% (by weight) of one or more liquid fats, and about 0.1% to about 40% (by weight) of one or more digestive stimulants. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 40% to about 50% (by weight) of one or more hard fats, about 30% to about 50% (by weight) of one or more liquid fats, and about 0.1% to about 40% (by weight) of one or more digestive stimulants. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0188] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 40% to about 50% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 40% to about 50% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0189] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, C10 -C 24 About 40% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 In some embodiments, the pharmaceutical composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive stimulants. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, C 10 -C 24 About 40% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 The composition comprises about 30% to about 50% (by weight) of one or more liquid fats including partially hydrolyzed triglycerides including a mixture of triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0190] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 40% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18 In some embodiments, the pharmaceutical composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive stimulants. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, saturated fatty acids, PEG-14 ... 10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 40% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18The composition comprises about 30% to about 50% (by weight) of one or more liquid fats including partially hydrolyzed triglycerides including a mixture of triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0191] In some embodiments, the pharmaceutical composition comprises fenofibrate, one or more hard fats, one or more liquid fats, and one or more digestive enhancers. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0192] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) fenofibrate, about 40% to about 50% (by weight) one or more hard fats, about 30% to about 50% (by weight) one or more liquid fats, and about 0.1% to about 40% (by weight) one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL fenofibrate, about 40% to about 50% (by weight) one or more hard fats, about 30% to about 50% (by weight) one or more liquid fats, and about 0.1% to about 40% (by weight) one or more digestive enhancers. In some embodiments, the one or more digestive enhancers are one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0193] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) fenofibrate, about 40% to about 50% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL fenofibrate, about 40% to about 50% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0194] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of fenofibrate, C 10 -C24 About 40% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 In some embodiments, the pharmaceutical composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, C 10 -C 24 About 40% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 The composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0195] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of fenofibrate, saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 40% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18In some embodiments, the pharmaceutical composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, saturated fatty acids, PEG-14, PEG-14C, PEG-14D, PEG-14E, PEG-14F, PEG-14H ... 10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 40% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18 The composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 40% (by weight) of one or more digestive enhancers. In some embodiments, the one or more digestive enhancers include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 a fatty acid surfactant, or any combination thereof.

[0196] In some embodiments, the pharmaceutical composition comprises one or more fibrates, one or more hard fats, one or more liquid fats, and one or more bile acids. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments comprise cholic acid.

[0197] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 40% to about 50% (by weight) of one or more hard fats, about 30% to about 50% (by weight) of one or more liquid fats, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 40% to about 50% (by weight) of one or more hard fats, about 30% to about 50% (by weight) of one or more liquid fats, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid.

[0198] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 40% to about 50% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 40% to about 50% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid.

[0199] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, C 10 -C 24 About 40% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24In some embodiments, the pharmaceutical composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, C 10 -C 24 About 40% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 The composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid.

[0200] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 40% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C18 Mono-, C 16 -C 18 Di- and C 16 -C 18 In some embodiments, the pharmaceutical composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 40% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18 The composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid.

[0201] In some embodiments, the pharmaceutical composition comprises fenofibrate, one or more hard fats, one or more liquid fats, and one or more bile acids, in some embodiments, the one or more bile acids in the above embodiments comprise cholic acid.

[0202] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) fenofibrate, about 40% to about 50% (by weight) one or more hard fats, about 30% to about 50% (by weight) one or more liquid fats, and about 0.1% to about 10% (by weight) one or more bile acids. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL fenofibrate, about 40% to about 50% (by weight) one or more hard fats, about 30% to about 50% (by weight) one or more liquid fats, and about 0.1% to about 10% (by weight) one or more bile acids. In some embodiments, the one or more bile acids in the above embodiments include cholic acid.

[0203] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) fenofibrate, about 40% to about 50% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL fenofibrate, about 40% to about 50% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the one or more bile acids in the above embodiments comprises cholic acid.

[0204] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of fenofibrate, C 10 -C 24About 40% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 In some embodiments, the pharmaceutical composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, C 10 -C 24 About 40% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 The composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the one or more bile acids in the above embodiments include cholic acid.

[0205] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of fenofibrate, saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 40% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18 In some embodiments, the pharmaceutical composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, saturated C10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 40% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18 The composition comprises about 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, and about 0.1% to about 10% (by weight) of one or more bile acids. In some embodiments, the one or more bile acids in the above embodiments include cholic acid.

[0206] In some embodiments, the pharmaceutical composition comprises one or more fibrates, one or more hard fats, one or more liquid fats, one or more bile acids, and one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; the one or more bile acids in the above embodiments include cholic acid; and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 The fatty acids include, preferably, oleic acid, steric acid, linoleic acid, or any combination thereof.

[0207] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 25% to about 50% (by weight) of one or more hard fats, about 30% to about 50% (by weight) of one or more liquid fats, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 25% to about 50% (by weight) of one or more hard fats, about 30% to about 50% (by weight) of one or more liquid fats, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; the one or more bile acids in the above embodiments include cholic acid; and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 The fatty acids include, preferably, oleic acid, steric acid, linoleic acid, or any combination thereof.

[0208] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% (by weight) of one or more fibrates, from about 25% to about 50% (by weight) of one or more hard fats comprising glycerolipids, from about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, from about 0.1% to about 10% (by weight) of one or more bile acids, and from about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 25% to about 50% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; the one or more bile acids in the above embodiments include cholic acid; and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 The fatty acids include, preferably, oleic acid, steric acid, linoleic acid, or any combination thereof.

[0209] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, C 10 -C 24 About 25% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C24 Mono-, C 10 -C 24 Di- and C 10 -C 24 About 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, C 10 -C 24 About 25% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 About 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; the one or more bile acids in the above embodiments include cholic acid; and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 The fatty acids include, preferably, oleic acid, steric acid, linoleic acid, or any combination thereof.

[0210] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18About 25% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18 About 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 25% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18 About 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; the one or more bile acids in the above embodiments include cholic acid; and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 The fatty acids include, preferably, oleic acid, steric acid, linoleic acid, or any combination thereof.

[0211] In some embodiments, the pharmaceutical composition comprises fenofibrate, one or more hard fats, one or more liquid fats, one or more bile acids, and one or more free C 14-24In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 The fatty acids include, preferably, oleic acid, steric acid, linoleic acid, or any combination thereof.

[0212] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) fenofibrate, about 25% to about 50% (by weight) one or more hard fats, about 30% to about 50% (by weight) one or more liquid fats, about 0.1% to about 10% (by weight) one or more bile acids, and about 5% to about 25% (by weight) one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, about 25% to about 50% (by weight) of one or more hard fats, about 30% to about 50% (by weight) of one or more liquid fats, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18The fatty acids include, preferably, oleic acid, steric acid, linoleic acid, or any combination thereof.

[0213] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) fenofibrate, about 25% to about 50% (by weight) one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, about 0.1% to about 10% (by weight) one or more bile acids, and about 5% to about 25% (by weight) one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, about 25% to about 50% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 50% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 The fatty acids include, preferably, oleic acid, steric acid, linoleic acid, or any combination thereof.

[0214] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of fenofibrate, C 10 -C 24About 25% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 About 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, C 10 -C 24 About 25% to about 50% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 About 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 The fatty acids include, preferably, oleic acid, steric acid, linoleic acid, or any combination thereof.

[0215] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of fenofibrate, saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 25% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18 About 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 About 25% to about 50% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Di- and C 16 -C 18 About 30% to about 50% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 5% to about 25% (by weight) of one or more free C 14-24 In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C14-24 Fatty acids contain one or more free C 14-18 The fatty acids include, preferably, oleic acid, steric acid, linoleic acid, or any combination thereof.

[0216] In some embodiments, the pharmaceutical composition comprises one or more fibrates, one or more hard fats, one or more liquid fats, one or more bile acids, one or more free C 14-24 Fatty acids and one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments comprises a fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18The surfactant may be a fatty acid surfactant, preferably an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the surfactant may be a fatty acid surfactant, preferably an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; in some embodiments, the one or more bile acids in the above embodiments include cholic acid; and in some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; the one or more bile acids in the above embodiments include cholic acid; and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; in some embodiments, the one or more bile acids in the above embodiments include cholic acid; and in some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof.

[0217] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 25% to about 40% (by weight) of one or more hard fats, about 30% to about 45% (by weight) of one or more liquid fats, about 0.1% to about 10% (by weight) of one or more bile acids, about 10% to about 25% (by weight) of one or more free C 14-24 Fatty acids, and about 0.1% to about 5% (by weight) of one or more free C 14-24In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 25% to about 40% (by weight) of one or more hard fats, about 30% to about 45% (by weight) of one or more liquid fats, about 0.1% to about 10% (by weight) of one or more bile acids, and about 10% to about 25% (by weight) of one or more free C 14-24 Fatty acids, and about 0.1% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments comprises a fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18The surfactant may be a fatty acid surfactant, preferably an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the surfactant may be a fatty acid surfactant, preferably an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; in some embodiments, the one or more bile acids in the above embodiments include cholic acid; and in some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; the one or more bile acids in the above embodiments include cholic acid; and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; in some embodiments, the one or more bile acids in the above embodiments include cholic acid; and in some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof.

[0218] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, about 25% to about 40% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 45% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, about 10% to about 25% (by weight) of one or more free C 14-24 Fatty acids and about 0.1% to about 5% (by weight) of one or more free C 14-24In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, about 25% to about 40% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 45% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, about 10% to about 25% (by weight) of one or more free C 14-24 Fatty acids and about 0.1% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments comprises a fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18The surfactant may be a fatty acid surfactant, preferably an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the surfactant may be a fatty acid surfactant, preferably an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; in some embodiments, the one or more bile acids in the above embodiments include cholic acid; and in some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; the one or more bile acids in the above embodiments include cholic acid; and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof; in some embodiments, the one or more bile acids in the above embodiments include cholic acid; and in some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof.

[0219] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% (by weight) of one or more fibrates, C 10 -C 24 About 25% to about 40% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24About 30% to about 45% (by weight) of one or more liquid fats including partially hydrolyzed triglycerides including a mixture of triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 10% to about 25% (by weight) of one or more free C 14-24 Fatty acids and about 0.1% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of one or more fibrates, C 10 -C 24 About 25% to about 40% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Di- and C 10 -C 24 About 30% to about 45% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 0.1% to about 10% (by weight) of one or more bile acids, and about 10% to about 25% (by weight) of one or more free C 14-24 Fatty acids, about 0.1% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments comprises a fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18The surfactant may be a fatty acid surfactant, preferably an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments include cholic acid. In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibrate, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, lonifibrate, simfibrate, or any combination thereof, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more fre...

Claims

1. A composition comprising one or more fibrates, one or more glycerolipids, one or more bile acids, one or more free C for use in the treatment of inflammation. １４ -C ２４ Fatty acid, one or more free C １４ -C ２４ a fatty acid surfactant, or any combination thereof; Pharmaceutical compositions.

2. The pharmaceutical composition of claim 1 , wherein the inflammation is neuroinflammation.

3. The pharmaceutical composition according to claim 1 or 2, wherein the fibrate is fenofibrate or fenofibric acid.

4. 4. The pharmaceutical composition of any one of claims 1 to 3, wherein the one or more glycerolipids are provided in an amount of 50% to 95% by weight of the composition.

5. 5. The pharmaceutical composition of claim 1, wherein the one or more glycerolipids comprise one or more hard fats and one or more liquid fats.

6. 6. The pharmaceutical composition of claim 5, wherein the one or more hard fats comprise glycerolipids that are solid at 18°C.

7. 7. The pharmaceutical composition of claim 5 or 6, wherein the one or more liquid fats consist of glycerolipids that are liquid at 18°C.

8. 7. The pharmaceutical composition of claim 5 or 6, wherein the one or more hard fats comprise one or more triglycerides.

9. The one or more triglycerides are saturated and / or unsaturated C １０－ C １８ Mixtures of triglycerides and / or saturated and / or unsaturated C １２－ C １８ 9. The pharmaceutical composition of claim 8, comprising or consisting of a mixture of triglycerides.

10. 8. The pharmaceutical composition of claim 5 or 7, wherein the one or more liquid fats comprise a mixture of mono-, di- and triglycerides.

11. The mixture of mono-, di- and triglycerides is １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ 11. The pharmaceutical composition of claim 10, comprising a mixture of triglycerides.

12. 55. A pharmaceutical composition according to any one of claims 49-51 and 53-54, wherein the one or more hard fats are provided at 25-40% by weight of the composition.

13. 13. The pharmaceutical composition of any one of claims 4, 5, 7, or 10-12, wherein the one or more liquid fats are provided at 30% to 45% by weight of the composition.

14. 14. The pharmaceutical composition according to any one of claims 4 to 13, wherein said one or more hard fats and said one or more liquid fats are in a hard fat to liquid fat ratio of 1:2 or 2:1, or preferably in a 1:1 ratio.

15. A pharmaceutical composition according to any one of claims 1 to 14, wherein the one or more fibrates are preferably in an amount of 0.1% to 25% by weight of the composition.

16. 16. The pharmaceutical composition of any one of claims 1-15, wherein the one or more bile acids comprise or consist of cholic acid, chenodeoxycholic acid, dafachronic acid, deoxycholic acid, glycocholic acid, glycohenodeoxycholic acid, lithocholic acid, taurochenodeoxycholic acid, taurocholic acid, any stereoisomers thereof, and any combination thereof.

17. 17. The pharmaceutical composition of any one of claims 1 to 16, wherein the one or more bile acids are provided in an amount of 0.1% to 10% by weight of the composition.

18. The one or more free C １４ -C ２４ Fatty acids include palmitic acid (hexadecenoic acid), palmitrinolenic acid, palmitidonic acid, palmitovaccenic acid, palmitoleic acid, sapienic acid, 4-hexadecenoic acid, stearic acid (octadecenoic acid), α-linolenic acid, stearidonic acid, α-eleostearic acid, β-eleostearic acid, pumic acid, 7,10,13-octadecatrienoic acid, 12-octadecenoic acid, linoleic acid, and linoelaidic acid. gamma-linolenic acid, calendic acid, pinolenic acid, vaccinic acid, ruminic acid, oleic acid, elaidic acid, petroselinic acid, arachidic acid (eicosanoic acid), dihomo-alpha-linolenic acid, eicosinic acid, traenoic acid, eicosapentaenoic acid, 9,12,15-eicosatrienoic acid, beta-eicosinic acid, traenoic acid, dihomo-linoleic acid, dihomo-gamma-linolenic acid, arachidonic acid, paulinic acid, 7,10,13-eicosatrienoic acid, gondoinic acid 18. The pharmaceutical composition of any one of claims 1 to 17, comprising 1,2,3,4,5,6,7,8,9,10,11-eicosadienoic acid, meazinic acid, gadoleic acid, 8-eicosenoic acid, behenic acid (docosanoic acid), clupanodonic acid, docosahexaenoic acid, adrenic acid, osbondic acid, erucic acid, lignoceric acid (tetracosanoic acid), 9,12,15,18,21-tetracosapentaenoic acid, 6,9,12,15,18,21-tetracosahexaenoic acid, and nervonic acid.

19. The one or more free C １４ -C ２４ 20. The pharmaceutical composition of claim 18, wherein the fatty acid comprises oleic acid, stearic acid, linoleic acid, or any combination thereof.

20. The one or more free C １４ -C ２４ 20. The pharmaceutical composition of any one of claims 1 to 19, wherein the fatty acid is provided in an amount of 10% to 25% by weight of the composition.

21. The one or more free C １４ -C ２４ Fatty acid surfactants include sodium palmitate (hexadecenoic acid), sodium palmitrinolenate, sodium palmitidate, sodium palmitovaccenate, sodium palmitoleate, sodium sapienate, sodium 4-hexadecenoate, sodium stearate (octadecenoic acid), sodium α-linolenate, sodium stearidonate, sodium α-eleostearate, sodium β-eleostearate, sodium pumicate, sodium 7,10,13-octadecatrienoate, sodium 12-octadecenoate, sodium linoleate, and sodium linoelaidate. Sodium gamma-linolenate, sodium calendate, sodium pinolenate, sodium vaccinate, sodium luminate, sodium oleate, sodium elaidate, sodium petroselinate, sodium arachidic acid (eicosanoic acid), sodium dihomo-alpha-linolenate, sodium eicosinate toraenoate, sodium eicosapentaenoate, sodium 9,12,15-eicosatrienoate, sodium beta-eicosinate toraenoate, sodium dihomo-linoleate, sodium dihomo-gamma-linolenate, sodium arachidonate, sodium paurate, sodium 7,10,13-eicosatrienoate, sodium gonolic acid, 21. The pharmaceutical composition according to any one of claims 1 to 20, wherein the active ingredient is selected from the list consisting of sodium indoinate, sodium 8,11-eicosadienoate, sodium meazinate, sodium gadoleate, sodium 8-eicosenoate, sodium behenate (docosanoate), sodium clupanodonate, sodium docosahexaenoate, sodium adrenate, sodium osbondate, sodium erucate, sodium lignocerate (tetracosanoate), sodium 9,12,15,18,21-tetracosapentaenoate, sodium 6,9,12,15,18,21-tetracosahexaenoate, and sodium nervonate.

22. The one or more free C １４ -C ２４ A pharmaceutical composition according to any one of claims 1 to 21, wherein the fatty acid surfactant is provided in an amount of 0.1 to 5% by weight of the composition.

23. The pharmaceutical composition according to any one of claims 1 to 22, wherein the pharmaceutical composition is not an emulsion or a self-emulsifying formulation.

24. 0.1% to 25% by weight of one or more fibrates, 25% to 40% by weight of one or more hard fats, 30% to 45% by weight of one or more liquid fats, 0.1% to 10% by weight of one or more bile acids, 10% to 25% by weight of one or more free C １４ -C ２４ fatty acids, and 0.1% to 5% by weight of one or more free C １４ -C ２４ A pharmaceutical composition according to any one of claims 5 to 23, comprising a fatty acid surfactant.

25. 1. A pharmaceutical composition for use in the treatment of neuroinflammation, comprising: Fenofibrate, about 30% to about 40% by weight of one or more hard fats, about 30% to about 40% by weight of one or more liquid fats, about 3% to about 6% by weight of one or more bile acids, about 15% to about 25% by weight of one or more free C １４－２４ fatty acids, and from about 0.5% to about 5% by weight of one or more free C １４－２４ Contains fatty acid surfactants, Pharmaceutical compositions.

26. About 10% to about 20% by weight of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 26% to about 36% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ From about 26% to about 36% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; from about 3% to about 7% by weight of one or more bile acids; from about 12% to about 22% by weight of one or more free C １４－２４ fatty acids and from about 0.5% to about 4% by weight of one or more free C １４－２４ 26. The pharmaceutical composition of claim 25, comprising a fatty acid surfactant.

27. About 12% to about 18% by weight of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 28% to about 34% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 28% to about 34% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; about 14% to about 20% by weight of one or more free C １４－２４ fatty acids and from about 0.8% to about 3% by weight of one or more free C １４－２４ 27. The pharmaceutical composition of claim 25 or 26, comprising a fatty acid surfactant.

28. About 14% to about 16% by weight of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 30% to about 32% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 30% to about 32% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 4% to about 6% by weight of one or more bile acids; about 16% to about 18% by weight of one or more free C １４－２４ fatty acids and from about 1% to about 1.4% by weight of one or more free C １４－２４ A pharmaceutical composition according to any one of claims 25 to 27, comprising a fatty acid surfactant.

29. About 25 mg / mL to about 300 mg / mL of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 28% to about 34% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 28% to about 34% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; about 14% to about 20% by weight of one or more free C １４－２４ fatty acids and from about 0.8% to about 3% by weight of one or more free C １４－２４ 26. The pharmaceutical composition of claim 25, comprising a fatty acid surfactant.

30. About 35 mg / mL to about 200 mg / mL of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 28% to about 34% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 28% to about 34% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; about 14% to about 20% by weight of one or more free C １４－２４ fatty acids and from about 0.8% to about 3% by weight of one or more free C １４－２４ 30. The pharmaceutical composition of claim 25 or 29, comprising a fatty acid surfactant.

31. About 70 mg / mL to about 150 mg / mL of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 30% to about 32% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 30% to about 32% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 4% to about 6% by weight of one or more bile acids; about 16% to about 18% by weight of one or more free C １４－２４ fatty acids and from about 1% to about 1.4% by weight of one or more free C １４－２４ 31. The pharmaceutical composition of claim 25, 29 or 30, comprising a fatty acid surfactant.

32. 32. The pharmaceutical composition of any one of claims 25 to 31, wherein the one or more bile acids comprises cholic acid.

33. The one or more free C １４－２４ The fatty acid has one or more free C １４－１８ The pharmaceutical composition according to any one of claims 25 to 32, comprising a fatty acid.

34. The one or more free C １４－１８ 34. The pharmaceutical composition of claim 33, wherein the fatty acid comprises oleic acid, stearic acid, linoleic acid, or any combination thereof.

35. The one or more free C １４－２４ The fatty acid surfactant may have one or more free C １４－１８ A pharmaceutical composition according to any one of claims 25 to 34, comprising a fatty acid surfactant.

36. The one or more free C １４－１８ 36. The pharmaceutical composition of claim 35, wherein the fatty acid surfactant comprises an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof.

37. The one or more free C １４－１８ 37. The pharmaceutical composition of claim 35 or 36, wherein the fatty acid surfactant comprises sodium oleate, sodium stearate, sodium linoleate, or any combination thereof.

38. 1. A method of treating an individual with neuroinflammation, comprising: The method includes administering to an individual in need thereof a pharmaceutical composition, the pharmaceutical composition comprising: fenofibrate; about 30% to about 40% by weight of one or more hard fats; about 30% to about 40% by weight of one or more liquid fats; about 3% to about 6% by weight of one or more bile acids; about 15% to about 25% by weight of one or more free C １４－２４ fatty acids, and from about 0.5% to about 5% by weight of one or more free C １４－２４ Contains fatty acid surfactants, method.

39. The pharmaceutical composition comprises about 10% to about 20% by weight of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 26% to about 36% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ From about 26% to about 36% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; from about 3% to about 7% by weight of one or more bile acids; from about 12% to about 22% by weight of one or more free C １４－２４ fatty acids and from about 0.5% to about 4% by weight of one or more free C １４－２４ 40. The method of claim 38, comprising a fatty acid surfactant, the administration of which reduces symptoms associated with said inflammation, thereby treating said individual.

40. The pharmaceutical composition comprises about 12% to about 18% by weight of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 28% to about 34% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 28% to about 34% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; about 14% to about 20% by weight of one or more free C １４－２４ fatty acids and from about 0.8% to about 3% by weight of one or more free C １４－２４ 40. The method of claim 38 or 39, comprising a fatty acid surfactant.

41. The pharmaceutical composition comprises about 14% to about 16% by weight of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 30% to about 32% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 30% to about 32% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 4% to about 6% by weight of one or more bile acids; about 16% to about 18% by weight of one or more free C １４－２４ fatty acids and from about 1% to about 1.4% by weight of one or more free C １４－２４ The method of any one of claims 38 to 40, comprising a fatty acid surfactant.

42. The pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 28% to about 34% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 28% to about 34% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; about 14% to about 20% by weight of one or more free C １４－２４ fatty acids and from about 0.8% to about 3% by weight of one or more free C １４－２４ 39. The method of claim 38 comprising a fatty acid surfactant.

43. The pharmaceutical composition comprises about 35 mg / mL to about 200 mg / mL of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 28% to about 34% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 28% to about 34% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; about 14% to about 20% by weight of one or more free C １４－２４ fatty acids and from about 0.8% to about 3% by weight of one or more free C １４－２４ 43. The method of claim 38 or 42, comprising a fatty acid surfactant.

44. The pharmaceutical composition comprises about 70 mg / mL to about 150 mg / mL of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 30% to about 32% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 30% to about 32% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 4% to about 6% by weight of one or more bile acids; about 16% to about 18% by weight of one or more free C １４－２４ fatty acids and from about 1% to about 1.4% by weight of one or more free C １４－２４ 44. The method of claim 38, 42 or 43, comprising a fatty acid surfactant.

45. 45. The method of any one of claims 38 to 44, wherein the one or more bile acids comprises cholic acid.

46. The one or more free C １４－２４ The fatty acid has one or more free C １４－１８ 46. ​​The method of any one of claims 38 to 45, comprising a fatty acid.

47. The one or more free C １４－１８ 47. The method of claim 46, wherein the fatty acid comprises oleic acid, stearic acid, linoleic acid, or any combination thereof.

48. The one or more free C １４－２４ The fatty acid surfactant may have one or more free C １４－１８ The method of any one of claims 38 to 47, comprising a fatty acid surfactant.

49. The one or more free C １４－１８ 49. The method of claim 48, wherein the fatty acid surfactant comprises an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof.

50. The one or more free C １４－１８ 50. The method of claim 48 or 49, wherein the fatty acid surfactant comprises sodium oleate, sodium stearate, sodium linoleate, or any combination thereof.

51. 23. Use of a pharmaceutical composition in the manufacture of a medicament for treating neuroinflammation, comprising: The pharmaceutical composition comprises fenofibrate, about 30% to about 40% by weight of one or more hard fats, about 30% to about 40% by weight of one or more liquid fats, about 3% to about 6% by weight of one or more bile acids, about 15% to about 25% by weight of one or more free C １４－２４ fatty acids, and from about 0.5% to about 5% by weight of one or more free C １４－２４ Contains fatty acid surfactants, use.

52. The composition comprises about 10% to about 20% by weight of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 26% to about 36% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ From about 26% to about 36% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; from about 3% to about 7% by weight of one or more bile acids; from about 12% to about 22% by weight of one or more free C １４－２４ fatty acids and from about 0.5% to about 4% by weight of one or more free C １４－２４ 52. The use of claim 51 comprising a fatty acid surfactant.

53. The composition comprises about 12% to about 18% by weight of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 28% to about 34% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 28% to about 34% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; about 14% to about 20% by weight of one or more free C １４－２４ fatty acids and from about 0.8% to about 3% by weight of one or more free C １４－２４ 53. The use according to claim 51 or 52, comprising a fatty acid surfactant.

54. The composition comprises about 14% to about 16% by weight of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 30% to about 32% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 30% to about 32% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 4% to about 6% by weight of one or more bile acids; about 16% to about 18% by weight of one or more free C １４－２４ fatty acids and from about 1% to about 1.4% by weight of one or more free C １４－２４ 54. The use according to any one of claims 51 to 53, comprising a fatty acid surfactant.

55. The composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 28% to about 34% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 28% to about 34% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; about 14% to about 20% by weight of one or more free C １４－２４ fatty acids and from about 0.8% to about 3% by weight of one or more free C １４－２４ 52. The use of claim 51 comprising a fatty acid surfactant.

56. The composition comprises about 35 mg / mL to about 200 mg / mL of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 28% to about 34% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 28% to about 34% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; about 14% to about 20% by weight of one or more free C １４－２４ fatty acids and from about 0.8% to about 3% by weight of one or more free C １４－２４ 56. The use according to claim 51 or 55, comprising a fatty acid surfactant.

57. The composition comprises about 70 mg / mL to about 150 mg / mL of fenofibrate, saturated C １０ -C １８ Triglycerides and / or saturated C １２ -C １８ From about 30% to about 32% by weight of one or more hard fats comprising a mixture of triglycerides; １６ -C １８ Mono-, C １６ -C １８ Ji and C １６ -C １８ About 30% to about 32% by weight of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides; about 4% to about 6% by weight of one or more bile acids; about 16% to about 18% by weight of one or more free C １４－２４ fatty acids and from about 1% to about 1.4% by weight of one or more free C １４－２４ 57. The use of claim 51, 55 or 56, comprising a fatty acid surfactant.

58. 58. The use of any one of claims 51 to 57, wherein the one or more bile acids comprises cholic acid.

59. The one or more free C １４－２４ The fatty acid has one or more free C １４－１８ 59. The use according to any one of claims 51 to 58, comprising a fatty acid.

60. The one or more free C １４－１８ 60. The use of claim 59, wherein the fatty acid comprises oleic acid, stearic acid, linoleic acid, or any combination thereof.

61. The one or more free C １４－２４ The fatty acid surfactant may have one or more free C １４－１８ 61. The use according to any one of claims 51 to 60, comprising a fatty acid surfactant.

62. The one or more free C １４－１８ 62. The use of claim 61, wherein the fatty acid surfactant comprises an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof.

63. The one or more free C １４－１８ 63. The use of claim 61 or 62, wherein the fatty acid surfactant comprises sodium oleate, sodium stearate, sodium linoleate, or any combination thereof.

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