Fettes compositions for treatment of inflammation and neuroinflammation

Abstract

The present specification discloses pharmaceutical compositions disclosed herein comprising one or more fibrates, one or more glycerolipids, and one or more digestion enhancers. The disclosed glycerolipids comprise one or more hard fats and one or more liquid fats. The disclosed digestion enhancers comprise one or more bile acids, one or more phospholipids, one or more free C14-24 fatty acids, one or more free C14-24 fatty acid surfactants, or any combination thereof. The present specification also discloses methods and procedures for formulating the disclosed one or more fibrates into the disclosed pharmaceutical compositions. Methods and uses of the disclosed pharmaceutical compositions in the treatment of inflammation and / or neuroinflammation are also disclosed.

Description

[0001] This application is an international patent application that claims the benefit of priority to and enjoys the filing date of U.S. Provisional Patent Application No. 63 / 362,005, filed on March 28, 2022, and U.S. Provisional Patent Application No. 63 / 269,327, filed on March 14, 2022, the contents of each of which are hereby incorporated by reference in their entirety.

[0002] Inflammation involves the activation of the immune system in response to harmful stimuli such as pathogens, infections, irritants or damage to cells. As a stereotyped response, inflammation is a mechanism of innate immunity compared to adaptive immunity, which is specific to each pathogen. Inflammation can be classified as acute or chronic. In general, 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 protective response to remove harmful stimuli by maintaining tissue integrity and promoting tissue repair. Acute inflammation is part of the body's natural defense system against injury and disease, and without acute inflammation, wounds and infections would never heal, and progressive tissue destruction would jeopardize the survival of the organism.

[0004] Acute inflammatory process is caused by the cell that already exists in all tissues, and described cell is mainly resident macrophage (resident macrophage), dendritic cell, tissue cell, Kupffer cell (Kupffer cell), mast cell, vascular endothelial cell and vascular smooth muscle cell.When harmful stimulation begins, these cell experiences activation and releases inflammatory mediation and sensitizing molecules, such as proinflammatory cytokines, proinflammatory prostaglandins, leukotrienes, histamine, serotonin, neutral protease, bradykinin and nitric oxide.These inflammatory molecules regulate the cellular components and a series of complicated biological events of cell-free components related to local vascular system, immune system and damaged tissue position, to propagate inflammatory response and make inflammatory response mature. These events lead to the initiation of an acute inflammatory response, which is typically characterized by 1) vasodilation, which increases blood flow into the tissue, causing erythema (redness and warmth), which may extend beyond the site (flushing response); 2) vascular permeability, which increases plasma leakage into the tissue, causing edema (swelling); 3) changes in the excitability of certain sensory neurons that cause hypersensitivity and pain; 4) stimulation of the release of inflammation-inducing molecules from peripheral nerve endings, such as, for example, neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), prostaglandins, and amino acids such as glutamate; and 5) increased migration of leukocytes (primarily granulocytes) from blood vessels into tissues. The acute inflammatory response requires continued stimulation to maintain and must be actively terminated when no longer needed. Therefore, once the noxious stimulus has been removed, acute inflammation ceases.

[0005] However, severe or prolonged noxious stimulation leads to a chronic inflammatory response that causes a progressive shift in the cell types present at the site of tissue damage. Chronic inflammation can be characterized as the simultaneous destruction and healing of tissues from the inflammatory process, with the net result being to induce damage rather than mediate repair. Therefore, chronic inflammation is a disease. Because the inflammatory response can occur anywhere in the body, chronic inflammation has been associated with a wide range of seemingly unrelated pathophysiological disorders that form the basis of a large and diverse group of human diseases. For example, chronic inflammation is involved in diseases such as cardiovascular disease, cancer, allergies, obesity, diabetes, digestive system diseases, degenerative diseases, autoimmune disorders, and Alzheimer's disease.

[0006] The success that the attempt that treats chronic inflammation has achieved is limited. This is partly due to the fact that the cause of disease of chronic inflammation is partly based on the complex response of multiple inflammation-inducing molecules and multiple inflammation-mediating and sensitizing molecules, and these molecules seem to cause inflammation via redundant mechanisms. In addition, in addition to blocking proinflammatory molecules, many anti-inflammatory drugs also suppress the regulatory loop that releases endogenous anti-inflammatory molecules. For example, NSAID reduces inflammation by blocking the enzymatic activity of cyclooxygenase, which is the key enzyme that catalyzes arachidonic acid to be converted into prostaglandins and leukotrienes. Therefore, NSAID reduces inflammation by preventing the synthesis of all prostaglandins. However, NSAID not only prevents the synthesis of proinflammatory prostaglandins, but these compounds also prevent the synthesis of anti-inflammatory prostaglandins. Therefore, the success that NSAID has is limited, because they block endogenous anti-inflammatory responses, which may prolong chronic inflammation in some cases. Therefore, the compounds, compositions, purposes and methods that preferentially suppress proinflammatory responses will be highly desirable for treating chronic inflammation.

[0007] Neuroinflammation is the inflammatory response of nervous tissue and can be acute and chronic.Acute neuroinflammatory response is the established defense for harmful conditions such as infection, toxins and neuronal cell damage.About the peripheral nervous system (PNS), neuroinflammatory response is processed in a manner similar to inflammatory response.The central nervous system (CNS) is considered to be an immune privileged site because the blood-brain barrier (BBB) ​​usually prevents peripheral immune cells from entering the CNS.Alternatively, in response to inflammatory triggers, the resident glial cells referred to as microglia become activated to destroy these infectious agents before the infectious agent damages nervous tissue, and are therefore the main form of active immune defense in the CNS.However, when the balance of anti-inflammatory signal conduction and pro-inflammatory signal conduction exists destruction, microglia become chronic activation, leading to the excessive production of proinflammatory factors (i.e., cytokines) and the progress of neurodegenerative changes (e.g., atrophy and loss of function of neurons).The activation of chronic neuroinflammation also triggers the infiltration of immune cells through the BBB from the periphery, accelerating neuroinflammation and neurodegenerative processes. Much research has focused on the central role of neuroinflammation in the pathogenesis of many CNS-related conditions, including, for example, traumatic brain injury, stroke, Alzheimer's disease, postoperative cognitive decline / perioperative neurocognitive disorders, and now even long-term cognitive side effects from SARS-CoV-2. However, attempts to treat neuroinflammation have had 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 description 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 and increase the bioavailability of one or more fibrates to better facilitate the treatment of both inflammation and neuroinflammation.

[0009] Overview

[0010] Aspects of the present specification disclose, in part, a pharmaceutical composition for treating inflammation, the pharmaceutical composition comprising a) one or more fibrates, b) one or more glycerolipids, and c) one or more digestion enhancers. The fibrates disclosed herein can be bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibride, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, nafenopin, ronifibrate and / or bisfibrate. The glycerolipids disclosed herein include hard fats and liquid fats. Hard fats are glycerolipids that are solid at 18°C ​​and include triglycerides. Liquid fats are glycerolipids that are liquid at 18°C ​​and also include partially hydrolyzed glycerolipids and monoglycerides. The digestion enhancers disclosed herein include one or more bile acids, one or more phospholipids, one or more free C 14-24 Fatty acid surfactants, one or more fatty acid salts, one or more fatty acid derivatives having a polyhydroxylated head group, one or more steroidal surfactants, or any combination thereof. The compositions disclosed herein may further comprise one or more pharmaceutically acceptable stabilizers.

[0011] Other aspects of the present specification disclose, in part, a pharmaceutical composition for treating neuroinflammation, the pharmaceutical composition comprising a) one or more fibrates, b) one or more glycerides, and c) one or more digestion enhancers. The fibrates disclosed herein can be bezafibrate, ciprofibrate, clinofibrate, clofibrate, clofibramide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthofibrate, ronifibrate and / or bisfibrate. The glycerides disclosed herein include hard fats and liquid fats. Hard fats are glycerides that are solid at 18°C ​​and include triglycerides. Liquid fats are glycerides that are liquid at 18°C ​​and also include partially hydrolyzed glycerides and monoglycerides. The digestion enhancers disclosed herein include one or more bile acids, one or more phospholipids, one or more free C 14-24 Fatty acid surfactants, one or more fatty acid salts, one or more fatty acid derivatives having a polyhydroxylated head group, one or more steroidal surfactants, or any combination thereof. The compositions disclosed herein may further comprise one or more pharmaceutically acceptable stabilizers.

[0012] Other aspects of the present specification disclose a method of treating an individual suffering from inflammation, comprising the step of administering to an individual in need thereof a composition disclosed herein, wherein the administration results in a reduction in symptoms associated with the inflammation, thereby treating the individual.

[0013] Other aspects of the present specification disclose a method of treating an individual suffering from neuroinflammation, comprising the step of administering to an individual in need thereof a composition disclosed herein, wherein the administration results in a reduction in symptoms associated with the neuroinflammation, thereby treating the individual.

[0014] Other aspects of the present specification disclose the use of the compositions disclosed herein in the manufacture of a medicament for treating inflammation.

[0015] Other aspects of the present specification disclose the use of the compositions disclosed herein in the manufacture of a medicament for treating neuroinflammation. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The accompanying drawings, which are incorporated into and constitute a part of this specification, illustrate aspects of the disclosed subject matter in at least one exemplary embodiment thereof, which exemplary embodiments are further defined in detail in the following description. According to one or more embodiments, features, elements, and aspects of the present disclosure are referenced by numerical symbols having the same numbers in different drawings, and the same numbers represent the same, equivalent, or similar features, elements, or aspects. The drawings are not necessarily to scale, but emphasis is placed on illustrating the principles described herein and provided by exemplary embodiments of the invention. In such drawings:

[0018] Figure 1A-Figure 1H A representative PXRD spectrum of the disclosed pharmaceutical composition comprising fenofibrate is shown, wherein Figure 1A Shown Representative PXRD spectrum of 43 / 01 standard; Figure 1B A representative PXRD spectrum of bile acid standards is shown; Figure 1C A representative PXRD spectrum of fenofibrate standard is shown; Figure 1D Representative PXRD spectra of vehicle standards are shown; Figure 1E shows a representative PXRD spectrum of the disclosed pharmaceutical composition comprising a fenofibrate standard; Figure 1F shows a representative PXRD spectrum of a fenofibrate standard superimposed on a representative PXRD spectrum of a disclosed pharmaceutical composition comprising a fenofibrate standard, wherein asterisks above peaks indicate relevant peak overlap; Figure 1G shows a representative PXRD spectrum of a cholic acid standard superimposed on a representative PXRD spectrum of a vehicle standard, where asterisks above peaks indicate relevant peak overlap; and Figure 1H shows a representative PXRD spectrum of a bile acid standard superimposed on a representative PXRD spectrum of a disclosed pharmaceutical composition comprising a fenofibrate standard, wherein asterisks above peaks indicate relevant peak overlap;

[0019] Figure 2A-2B Representative UHPLC traces of fenofibric acid levels in blood and brain are shown, where Figure 2A shows a UHPLC trace of fenofibric acid levels in blood following oral administration of 30 mg / kg of the disclosed pharmaceutical composition comprising fenofibrate; and Figure 2B shows a UHPLC trace of fenofibric acid levels in the brain following oral administration of 30 mg / kg of the disclosed pharmaceutical composition comprising fenofibrate;

[0020] Figure 3A-3B Representative UHPLC traces of fenofibric acid levels in blood and brain are shown, where Figure 3A shows a UHPLC trace of fenofibric acid levels in blood following oral administration of 30 mg / kg of the disclosed pharmaceutical composition comprising fenofibrate; and Figure 3B shows a UHPLC trace of fenofibric acid levels in the brain following oral administration of 30 mg / kg of the disclosed pharmaceutical composition comprising fenofibrate;

[0021] Figure 4 shows representative UHPLC traces 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 composition comprising fenofibrate;

[0022] Figures 5A-5F Shown is a bar graph of blood cytokine levels in animals subjected to a 5-day LPS challenge where treatment occurs only on day 1 of the LPS challenge, Figure 5A IL-1β levels are shown; Figure 5B IL-6 levels are shown; Figure 5C TNFα levels are shown; Figure 5D MCP-1 levels are shown; Figure 5E IL-10 levels are shown; and Figure 5F MCP-2 levels are shown (bars represent SEM, *=p<0.05, **=p<0.01, ***=p<0.001 relative to vehicle control);

[0023] Figures 6A-6F Shown is a bar graph of blood cytokine levels in animals that underwent 5 days of pretreatment prior to a 5-day LPS challenge, where Figure 6A IL-1β levels are shown; Figure 6BIL-6 levels are shown; Figure 6C TNFα levels are shown; Figure 6D MCP-1 levels are shown; Figure 6E IL-10 levels are shown; and Figure 6F MCP-2 levels are shown (bars represent SEM, *=p<0.05, **=p<0.01, ***=p<0.001);

[0024] Figures 7A-7F Shown is a bar graph of brain cytokine levels in animals subjected to a 5-day LPS challenge where treatment occurs only on day 1 prior to the initial LPS challenge. Figure 7A IL-1β levels are shown; Figure 7B IL-6 levels are shown; Figure 7C TNFα levels are shown; Figure 7D MCP-1 levels are shown; Figure 7E IL-10 levels are shown; and Figure 7F MCP-2 levels are shown (bars represent SEM, *=p<0.05, **=p<0.01, ***=p<0.001 relative to vehicle control);

[0025] Figures 8A-8F Shown is a bar graph of brain cytokine levels in animals that underwent 5 days of pretreatment prior to a 5-day LPS challenge, where Figure 8A IL-1β levels are shown; Figure 8B IL-6 levels are shown; Figure 8C TNFα levels are shown; Figure 8D MCP-1 levels are shown; Figure 8E IL-10 levels are shown; and Figure 8F MCP-2 levels are shown (bars represent SEM, *=p<0.05, **=p<0.01, ***=p<0.001 relative to vehicle control);

[0026] Figures 9A-9D Representative images of IBA-1 per high power field (HPF, x400) in the brain are shown in hippocampal and cortical slices. + cells and CD-68 + A histogram of the percentage levels of cells where Figure 9A Shown are the percentage levels of cells present in hippocampal sections stained with anti-IBA-1 antibody; Figure 9B The percentage levels of cells present in hippocampal sections stained with anti-CD-68 antibody are shown; Figure 9C The percentage levels of cells present in cortical sections stained with anti-IBA-1 antibody are shown; Figure 9DShown are 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 relative to vehicle control, #=p<0.05, ##=p<0.01, ###=p<0.001 relative to CMF2); and

[0027] Figure 10 is a bar graph showing fenofibric acid levels in cerebrospinal fluid (CSF) acid after oral administration of 70 mg, 140 mg, and 125 mg of the disclosed pharmaceutical composition comprising fenofibrate (bars represent minimum and maximum concentrations measured; * = mean; and boxes represent Q1 (upper box) and Q3 (lower box), where the line separating the Q1 box and the Q3 box represents the median value).

[0028] describe

[0029] Fibrates are fibric acid derivatives and a class of amphipathic carboxylic acids. Fibrates activate peroxisome proliferator-activated receptors (PPAR), particularly PPARα. PPAR is a class of ligand-activated nuclear receptors that regulates carbohydrate (or glucose) and fat metabolism, adipose tissue differentiation, endothelial function and inflammation. PPAR antagonism mediates lipid level regulation properties, such as, for example, by increasing lipolysis, activating lipoprotein lipase and reducing apoprotein C-III to reduce triglycerides and LDL and increase the level of HDL. Therefore, fibrates are considered to be hypolipidemic agents, and have been used for a series of metabolic disorders, mainly hypercholesterolemia (high cholesterol). PPAR agonism also causes a phenotypic shift from M1 / TH1 proinflammatory to M2 / TH2 anti-inflammatory, and PPAR receptor agonism works in a complementary manner to COX inhibition to allow inflammation to fully subside.

[0030] Fenofibrate is an example of a fibrate. This compound is a fibric acid derivative comprising fenofibric acid linked to an isopropyl ester. In vivo, the isopropyl ester of fenofibrate is completely hydrolyzed by liver carboxylesterase 1 to produce fenofibric acid. Therefore, fenofibrate can be considered a prodrug of fenofibric acid. Interestingly, both fenofibrate and fenofibric acid exhibit complementary pharmacology, which allows complete resolution of inflammation. For example, the main anti-inflammatory effect of fenofibric acid involves its PPARα agonist activity mediated by multiple mechanisms. On the other hand, fenofibrate mediates most of its anti-inflammatory activity by inhibiting selective cyclooxygenase 2 (COX2) activity and stimulating cannabinoid receptor type 2 (CB2).

[0031] Therefore, one advantage of utilizing the combined activity of fenofibrate and fenofibric acid to treat inflammation is their ability to influence three independent signaling pathways that mediate the inflammatory response. Furthermore, unlike traditional NSAIDs and selective COX2 inhibitors, fenofibrate and fenofibric acid have no gastric erosive potential and similarly no cardiac vulnerability. Therefore, the ability to fully resolve inflammation by utilizing the activity of fenofibrate and fenofibric acid would be of great benefit.

[0032] One obstacle to utilizing these three complementary pharmacologies in addressing inflammation is the rate at which fenofibrate is converted to fenofibric acid. The rapid hydrolysis of fenofibrate severely limits the therapeutic effect that this compound can exert. Therefore, a formulation that can slow, but not prevent, the conversion of fenofibrate to fenofibric acid would be advantageous in eliciting 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 increase the therapeutic effect of fenofibrate in the blood, the disclosed pharmaceutical composition surprisingly enables the delivery of both fenofibrate and fenofibric acid to the brain, thereby enhancing the ability of these fibrates to treat neuroinflammation.

[0033] Almost all of the digestion of dietary organic macromolecules and the absorption of the resulting decomposition products all occur in the small intestine. The luminal wall of the small intestine is lined with many protrusions that are called villi, and each protrusion includes intestinal cells that are called enterocytes. Enterocytes not only secrete enzymes that digest proteins (polypeptides), carbohydrates (polysaccharides) and fats (lipids), but also absorb amino acids, monosaccharides and fatty acid decomposition products. However, it is interesting that enterocytes process these decomposition products in a different way, wherein amino acids and monosaccharides are absorbed by capillaries and transported throughout the body by the blood system, and fatty acids are absorbed by the blind lymphatic vessels that are called lacteals and then transported throughout the body by the lymphatic system. Disclosed pharmaceutical compositions utilize this difference to process by preparing fibrates, which are preferentially processed by enterocytes in a way that these compounds are absorbed and transported to the lymphatic system.

[0034] The dietary lipids typically consumed by mammals consist of 90% triglycerides, along with smaller 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, but instead aggregate 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 hydrophilic nature, lipase remains in the intestinal fluid and cannot dissolve into fat globules, and can therefore only access and cleave triglycerides located at the surface of the interface between the fat globules and 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 amphiphilic molecules such as bile salts, including sodium cholate and sodium chenodeoxycholate; phospholipids, including lecithin; and the hydrophobic steroid cholesterol. When bile is excreted into the small intestine, it mixes with fat globules in a way that bile salts and phospholipids embed into these structures and break them down into smaller units called emulsion droplets, recruiting amphiphilic molecules called colipases. Colipase is a protein coenzyme that binds lipase to the emulsion droplets and stabilizes the enzyme in its active conformation. Thus, emulsification greatly increases the surface area on which lipase can act on triglycerides and increases its efficiency and catalytic rate, allowing sufficient lipid digestion to occur in the small intestine.

[0035] Along with the carrying out of lipid triglyceride digestion, the resulting free fatty acids (which are also hydrophobic and insoluble in intestinal juice) associate with the phospholipids from bile to form a tiny droplet that is called a mixed micelle, and the mixed micelle has the phospholipids and bile salt compositions that encapsulate free fatty acids. The mixed micelles that are about 200 times to 500 times smaller than the emulsion droplets merge with the intestinal epithelial cell membrane, and wherein the free fatty acids enter the cytosol of these cells. Once inside the intestinal epithelial cells, the free fatty acids are transported to the lumen of the smooth endoplasmic reticulum and converted back to triglycerides, which are assembled into spherical lipid structures with cholesterol and phospholipids. These lipid structures are transported to the rough endoplasmic reticulum, where apoprotein Apo B-48 is attached to the surface to form a large lipoprotein that is called chylomicrons. Then chylomicrons are packaged in the Golgi apparatus and leave the basolateral side of the intestinal epithelial cells via exocytosis. Because chylomicrons are too large to be absorbed by capillaries, these lipoproteins enter the lymphatic system via the lacteals in a process that relies on Apo B-48. Chylomicrons then circulate through the lymphatics and are discharged into the bloodstream via the thoracic duct, bypassing the liver. Once in the bloodstream, these lipoproteins travel 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. When most of the triglycerides have been hydrolyzed, chylomicron remnants are formed and absorbed by the liver, thereby also transferring dietary fat to this organ.

[0036] This specification discloses pharmaceutical compositions formulated for oral delivery in which the fibrates present in the pharmaceutical compositions are preferentially absorbed into the lymphatic system. The pharmaceutical compositions disclosed herein comprise one or more fibrates, one or more glycerolipids, and one or more digestion enhancers. The digestion enhancers disclosed herein increase the solubility of the one or more fibrates in the glycerolipid matrix, bind to the glycerolipids, increase the absorption of these compounds into the lymphatic system, and increase the availability of these compounds to their therapeutic targets.

[0037] The natural digestive process relies on bile secretion into the intestinal contents of intake, and relies on the mixing of bile and intestinal contents to trigger emulsification and the activity of other digestive processes such as lipase. In order for the drug to be absorbed, these processes must be completed. The complete gallbladder reaction associated with lipid intake will secrete up to 50mL-60mL of bile into the duodenum. The present invention relies on the close mixing of digestion enhancers and fibrates in the preparation of the pharmaceutical composition disclosed herein, which can then be taken orally by the patient. The fibrates are then presented to the intestinal cavity in a form ready for immediate ingestion. This process is highly effective because the digestion enhancers are closely mixed with the formulation lipid excipients. Without wishing to be bound by any theory, the pharmaceutical composition disclosed herein uses components as triglyceride digestion products to simulate the conditions produced by a high-fat meal. These preparations enable one or more fibrates contained therein to be bundled into micelles together with free fatty acids and absorbed by intestinal epithelial cells, which then package 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. Essentially, chylomicrons are co-opted as a drug delivery system for the one or more fibrates included in the pharmaceutical compositions disclosed herein. By controlling the composition and amount of the one or more glycerolipids and the one or more digestion-enhancing agents, the disclosed pharmaceutical compositions provide more consistent and predictable bioavailability of the one or more fibrates disclosed herein, which could previously be achieved through reliance on high-fat meals.

[0038] Pharmaceutical compositions disclosed herein are advantageous for several reasons, all of which ultimately increase the bioavailability and effectiveness of one or more fibrates contained therein. For example, pharmaceutical compositions disclosed herein deliver their fibrates via the lymphatic system. Using the lymphatic system to deliver fibrates is beneficial for several reasons. First, the lymphatic system avoids pre-systemic metabolism (pre-systemic metabolism) that reduces the bioavailability of many fibrates administered using traditional oral delivery methods. Also known as first-pass effect or first-pass metabolism, fibrates absorbed by the digestive system must first enter the hepatic portal vein system before arriving at the systemic circulation. And in the hepatic portal vein system, fibrates can be metabolized by the liver enzymes of the liver, which reduces the amount of fibrates entering the systemic circulation. Therefore, for fibrates susceptible to liver metabolism, delivering fibrates via the lymphatic system serves as a bypass to the hepatic portal vein system. The lymphatic uptake system represents an attractive opportunity for the preferential delivery of drugs. However, the small water-soluble molecules that comply with paracellular absorption rules (such as the Lipinski rule) are not ideal substrates for lymphatic uptake. Other highly lipophilic molecules are often poorly and variably bioavailable even when absorbed via lymphatic uptake.The present invention utilizes a broad family of digestion enhancers in lipid delivery systems to allow for the effective delivery of both small molecule Lipinski compliant drugs and highly lipophilic drugs via the lymphatic uptake route.

[0039] In addition, the lymphatic administration route can help fibrates to be directly delivered to its target cells, thereby increasing its bioavailability and reducing its clearance rate.For example, the chylomicrons of the loading fibrates transported to the lymphatic system will be discharged in the thoracic artery and circulate in the whole body via the arterial system, until arriving at the capillary bed, the chylomicrons of the loading fibrates in the capillary bed are exuded into the peripheral tissue to be absorbed by the target cells. The chylomicrons of the loading fibrates not absorbed by the target cells are removed from the extracellular environment by interstitial fluid, and in the interstitial fluid, they are absorbed by the lacteals, transported by the lymphatic system, and discharged in the thoracic artery, the chylomicrons of the loading fibrates in the thoracic artery will be recirculated to the whole body again. Due to avoiding the hepatic portal vein system discussed above, such application based on lymph causes more fibrates to be delivered to various systems, organs and tissues. In addition, because more fibrates enter the systemic circulatory system, its elimination (that is, metabolism and excretion) is extended, thereby reducing the clearance rate of the compound, which effectively increases its half-life.

[0040] Another advantage of the disclosed pharmaceutical composition is that one or more fibrates contained therein are selectively biodistributed to immune cells such as macrophages and dendritic cells using chylomicrons. For example, there are several processes by which macrophages can absorb chylomicrons. First, macrophages circulating in the lymph and blood secrete lipoprotein lipase, and chylomicrons are substrates for this enzymatic activity, leading to the uptake of chylomicron proteins and lipids, and by extension, leading to the uptake of any fibrates contained in the chylomicrons. In addition, the exogenous lipoprotein metabolic pathway converts chylomicrons into LDL particles through a series of processing events, and the LDL particles are oxidized by ROS to produce oxidized LDL particles. The FAT / CD36 scavenger receptors located on the macrophage membrane bind to and endocytose these oxidized LDL particles, including any fibrates contained therein. Ultimately, these macrophages loaded with fibrates will be directed to cells experiencing pathological pain, where fibrates can be delivered to these cells experiencing pain.

[0041] In addition, 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. It is also suspected that, because these micelles share structural similarities with chylomicrons, these micelles can also be absorbed via the macrophage lipoprotein lipase process discussed above.

[0042] The disclosed pharmaceutical compositions are also advantageous because the components used in their formulations mimic the signals that trigger bile and pancreatic lipoprotein lipase secretion, increase the rate of micelle formation, and increase the rate of intestinal epithelial cell absorption of the micelles to a rate higher than that achieved by using digestion enhancers alone in the formulation. Such features increase the rate and amount of fibrates entering the lymphatic system and thus increase their bioavailability.

[0043] In addition to preferential uptake into the lymphatic system and selective biodistribution to immune cells, the disclosed pharmaceutical compositions also have several additional advantages. For example, fibrates are poorly water-soluble or hydrophobic therapeutic compounds that have been proven difficult to formulate in a therapeutically effective manner due to, for example, their insolubility or instability in solution leading to precipitation. In addition, it has been surprisingly discovered that significantly higher concentrations of fibrates can be formulated in the pharmaceutical compositions disclosed herein relative to currently known formulations. Furthermore, the disclosed pharmaceutical compositions comprising one or more fibrates significantly increase the dissolution rate and bioavailability of these compounds.

[0044] Yet another advantage of the disclosed pharmaceutical compositions is the enhanced specificity for the cellular targets of one or more fibrates. Chylomicrons contain membrane-bound proteins that serve as ligands for their cognate receptors located on the membrane surface of the cell. One such ligand for these large lipoprotein particles is a protein that interacts with lipid transfer proteins. When chylomicrons loaded with fibrates 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 membranes, allowing passage through the blood-brain barrier and other epithelial tissues such as the choroid plexus. Thus, this mechanism increases the effectiveness of these compounds. Other cells that express high levels of lipid transfer proteins on their cell membranes include immune cells, cardiac cells, adipocytes, hepatocytes, and cancer cells. Cardiac cells express high levels of lipid transfer proteins on their surface, and therefore we can expect increased cardiotoxicity of therapeutic compounds delivered via the lymphatic route. However, the cardiotoxicity of therapeutic compounds is usually due to high C max The results suggest that lipid-based delivery of therapeutic compounds can lead to lower cardiac toxicity than expected, as these targets are protected from high concentrations of free compounds due to their slow release from the chylomicron phase. Therefore, the use of the pharmaceutical compositions disclosed herein can also be associated with reduced cardiac side effects and decreased toxicity. Furthermore, after ingestion, the therapeutic compound remains embedded in the oily / fatty excipient, limiting the opportunity for the compound to become dissolved in the aqueous intestinal contents, thereby avoiding contact toxicity such as gastric erosion and other local damage or injury. In addition to avoiding first-pass metabolism and local toxicity, enhanced uptake via the lymphatic route also minimizes the exposure and availability of free therapeutic compounds down the digestive tract. In this way, interactions and disruption of the intestinal microbiome can be minimized. This is a particular benefit when using this technology with antimicrobial agents. Furthermore, due to the anatomical structure of the lymphatic system, the lungs can be effectively targeted with appropriate drugs. For example, using this technology, anti-inflammatory drugs, anti-fibrotic drugs, antimicrobial drugs, and bronchodilators can be considered for lung targeting via lymphatic delivery.

[0045] In addition, the disclosed pharmaceutical composition is different from current surfactant-based formulations, such as, for example, coarse emulsions, 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 composition is not an emulsion or self-emulsifying composition, and therefore avoids the side effects associated with these formulations, such as causing irritation by making the membrane lining in the stomach unstable. In addition, the disclosed pharmaceutical composition avoids the manufacturing problems associated with current surfactant-based formulations, such as, for example, formulation processing problems and the absence of predictive in vitro testing. The disclosed pharmaceutical composition also avoids the problems associated with current surfactant-based formulations, including, for example, drug precipitation in vivo, limited lymphatic uptake, and the lack and oxidation of unsaturated fatty acids. Surprisingly, by simulating the microenvironment of mixed micelles, the disclosed pharmaceutical composition completely bypasses the dissolution stage of drug uptake, resulting in a significantly greater bioavailability of one or more fibrates contained therein. Unlike the self-emulsifying systems described above, the formulations disclosed herein are designed to avoid forming stable emulsions and do not undergo spontaneous emulsification (exhibiting the Ouzo Effect) when added to water. Instead, these materials are clearly immiscible when added to water.

[0046] Pharmaceutical composition

[0047] Aspects of this specification sheets partially disclose a composition. Compositions disclosed herein are generally used as pharmaceutically acceptable compositions. As used herein, the term "pharmaceutically acceptable" refers to any molecular entity or composition useful in the preparation of a pharmaceutical composition, which is generally safe, nontoxic, and neither biologically undesirable nor otherwise undesirable, and includes molecular entities or compositions acceptable for veterinary use and human pharmaceutical use. As used herein, the term "pharmaceutically acceptable composition" is synonymous with "pharmaceutical composition," and means the combination of one or more fibrates disclosed herein, which is combined with one or more glycerides, one or more digestion enhancers, and other components disclosed herein to form a product that is administered to an individual. Pharmaceutical compositions disclosed herein can be used for medical and veterinary applications. Pharmaceutical compositions can be administered to an individual individually, or combined with other supplementary active ingredients, agents, drugs, or hormones to administer to an individual.

[0048] This specification discloses pharmaceutical compositions that can be used to formulate one or more fibrates. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more glycerides, and c) one or more digestion enhancers. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates, b) one or more glycerides, c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24 Fatty acid surfactants or any combination thereof. 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 Fatty acid surfactant.

[0049] In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates; b) one or more triglycerides, including one or more partially hydrolyzed glycerides of a mixture of monoglycerides, diglycerides, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerides; and c) one or more digestion enhancers. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates; b) one or more triglycerides, including one or more partially hydrolyzed glycerides of a mixture of monoglycerides, diglycerides, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerides; c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24Fatty acid surfactants or any combination thereof. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more fibrates; b) one or more triglycerides, including one or more partially hydrolyzed glycerides of a mixture of monoglycerides, diglycerides, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerides; 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, including one or more partially hydrolyzed glycerides of a mixture of monoglycerides, diglycerides, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerides; 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 Fatty acid surfactant.

[0050] 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 digestion 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 Fatty acid surfactants or any combination thereof. 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 Fatty acid surfactant.

[0051] Pharmaceutical compositions disclosed herein are formulated as anhydrous solids, solid dispersions or molecular dispersions. Therefore, the preparations of the disclosed pharmaceutical compositions do not contain any water. In addition, as discussed above, the disclosed pharmaceutical compositions are not emulsions or self-emulsifying compositions. Therefore, pharmaceutical compositions disclosed herein will maintain their hydrophobic lipid characteristics when in an aqueous environment, behave just like fats and oils and require lipid digestion processes to be broken down for absorption. Emulsification will only occur when exposed to pancreatic juice from the small intestine. One reason is that the one or more glycerolipids and one or more digestion enhancers used are not sufficiently amphiphilic to induce emulsification, and need to be acted upon by the bile secreted by the gallbladder during the digestion process so that these components contribute to the formation of micellar structures. Another reason is that bile acids, fatty acid surfactants, phospholipids and any other digestion enhancers are all individually and in combination lower than the critical micelle concentration required for emulsification to occur.

[0052] Fibrates

[0053] Aspects of the present specification disclose, in part, fibrates. Examples of suitable fibrates include, but are not limited to, bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, and simfibrate. Fibrates have a higher lipophilicity or hydrophobicity, wherein 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, clobemide 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, naphthopine has a logP of 4.9, ronifibrate has a logP of 3.9, and simfibrate has a logP of 6.2.

[0054]

[0055] Regarding the other fibrates, namely bezafibrate, ciprofibrate, and gemfibrozil, these compounds exist in the acid form, whereas fenofibrate, clofibrate, ronifibrate, and simfibrate are fibric acid derivative esters. In addition to being a PPARα agonist, bezafibrate may also have some agonist activity on PPARγ and PPARδ.

[0056]

[0057]

[0058] In one embodiment, a pharmaceutical composition disclosed herein comprises one or more fibrates in an amount of, for example, 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 of, for example, at least 0.05%, at least 0.1%, at least 1%, at least 2.5%, at least 5%, at least 7.5%, at least 10%, at least 12.5%, at least 15%, at least 17.5%, at least 20%, at least 22.5%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, or at least 50% by weight. In one embodiment, a pharmaceutical composition disclosed herein comprises one or more fibrates in an amount of, e.g., at most 0.05%, at most 0.1%, at most 1%, at most 2.5%, at most 5%, at most 7.5%, at most 10%, at most 12.5%, at most 15%, at most 17.5%, at most 20%, at most 22.5%, at most 25%, at most 30%, at most 35%, at most 40%, at most 45%, or at most 50% by weight.

[0059] In one embodiment, a pharmaceutical composition disclosed herein comprises one or more fibrates disclosed herein in an amount of, 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 30%, about 0.05% to about 50%, about 0.05% to about 60%, about 0.05% to about 70%, about 0.05% to about 80%, about 0.05% to about 90%, about 0.05% to about 100%, about 0.05% to about 120%, about 0.05% to about 150%, about 0.05% to about 170%, about 0.05% to about 180%, about 0.05% to about 190%, about 0.05% to about 20 ...190%, about 0.05% to about 190%, about 0.05% to about 22.5%, about 0.05% to about 25%, 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%, From about 1% to about 40%, from about 1% to about 50%, from about 5% to about 10%, from about 5% to about 20%, from about 5% to about 30%, from about 5% to about 40%, from about 5% to about 50%, from about 10% to about 20%, from about 10% to about 30%, from about 10% to about 40%, from about 10% to about 50%, from about 20% to about 30%, from about 20% to about 40%, from about 20% to about 50%, from about 30% to about 40%, from about 30% to about 50%, or from about 40% to about 50%.

[0060] In one embodiment, a pharmaceutical composition disclosed herein comprises 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, a pharmaceutical composition disclosed herein comprises one or more fibrates at 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 at a concentration of, for example, at most 10 mg / mL, at most 15 mg / mL, at most 20 mg / mL, at most 25 mg / mL, at most 30 mg / mL, at most 35 mg / mL, at most 40 mg / mL, at most 45 mg / mL, at most 50 mg / mL, at most 60 mg / mL, at most 65 mg / mL, at most 70 mg / mL, at most 75 mg / mL, at most 100 mg / mL, at most 125 mg / mL, at most 150 mg / mL, at most 175 mg / mL, at most 200 mg / mL, at most 225 mg / mL, at most 250 mg / mL, at most 275 mg / mL, or at most 300 mg / mL.

[0061] In one embodiment, a pharmaceutical composition disclosed herein comprises one or more fibrates at a concentration of, 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 to about 250 mg / mL, about 25 mg / mL to about 300 mg / mL, about 50 mg / mL to about 100 mg / mL, about 50 mg / mL to about 150 mg / mL, about 50 mg / mL to about 200 mg / mL , about 50 mg / mL to about 250 mg / mL, about 50 mg / mL to about 300 mg / mL, about 75 mg / mL to about 100 mg / mL, about 75 mg / mL to about 150 mg / mL, about 75 mg / mL to about 200 mg / mL, about 75 mg / mL to about 250 mg / mL, about 75 mg / mL to about 300 mg / mL, about 100 mg / mL to about 150 mg / mL, about 100 mg / mL to about 200 mg / mL, about 100 mg / mL to about 250 mg / mL, about 100 mg / mL to about 30 In some embodiments, the present invention provides an intravenous injection of the pharmaceutical composition of the present invention. The intravenous injection of the pharmaceutical composition of the present invention may be performed at a dosage of about 100 mg / mL, about 125 mg / mL to about 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.

[0062] Glycerides

[0063] The pharmaceutical compositions disclosed herein may comprise one or more glycerolipids. Glycerolipids primarily comprise monosubstituted glycerol, disubstituted glycerol, and trisubstituted glycerol, and are hydrophobic molecules with an HLB of less than 4. One group of glycerolipids are glycerides, in which one, two, or all three hydroxyl groups of glycerol are each esterified with fatty acids to produce monoglycerides, diglycerides, and triglycerides, respectively. In these compounds, each hydroxyl group of glycerol can be esterified with the same fatty acid or with different fatty acids. In some embodiments, the monoglycerides disclosed herein may comprise glycerides having C 12 -C 24 In some embodiments, the diglycerides disclosed herein may comprise a saturated or unsaturated fatty acid having a carbon length of 12 -C 24 A saturated or unsaturated fatty acid of carbon length, or two fatty acids each having C 12 -C 24 In some embodiments, the triglycerides disclosed herein may comprise a saturated or unsaturated fatty acid having a carbon length of 12 -C 24 saturated or unsaturated fatty acids of carbon length, two fatty acids each having C 12 -C 24 A saturated or unsaturated fatty acid or three fatty acids each having a carbon length of 12 -C 24 Saturated or unsaturated fatty acids of carbon length.

[0064] Two types of glycerides are used to prepare one or more fibrates disclosed herein to produce pharmaceutical compositions disclosed herein. One type is hard fat, i.e., a glyceride that is solid at 18°C. Disclosed hard fats or glycerides that are solid at 18°C ​​have several purposes. During the preparation process of the pharmaceutical compositions disclosed herein, hard fats are compounded with the fibrates disclosed herein to stabilize them in the glyceride matrix and prevent the compound from precipitating. In addition, during the administration of the pharmaceutical compositions disclosed herein, the hard fats disclosed herein trigger the lipid digestion process, stimulating bile to be released from the gallbladder to enhance the emulsification of the administered pharmaceutical compositions. In addition, the hard fats present in the pharmaceutical compositions 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 triggers their absorption by the intestinal epithelial cells lining the lumen of the duodenum of the small intestine, along with the related fibrates. Once internalized, the intestinal epithelial cells subsequently process the free fatty acid / fibrate mixture and distribute it to the lymphatic system. The disclosed hard fats or glycerides 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 glycerides that are solid at 18° C. is to prevent formulation components that do have a critical micelle concentration from initiating emulsification by diluting the formulation components below their critical micelle concentration and providing an anhydrous environment that reduces the interactions required for these components to initiate emulsification.

[0065] Other types of glycerolipids used to formulate one or more fibrates disclosed herein are liquid fats or oils, i.e., glycerolipids that are liquid at 18°C. The primary purpose of the disclosed liquid fats or glycerolipids that are liquid at 18°C ​​is to serve as solvents that promote the dissolution of the fibrates disclosed herein and as stabilizers that prevent the disclosed fibrates from precipitating out of the glycerolipid matrix. The disclosed liquid fats or glycerolipids that are liquid 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 liquid fats or glycerolipids that are liquid at 18°C ​​is to prevent formulation components that do have a critical micelle concentration from initiating emulsification by diluting the formulation components below their critical micelle concentration and providing an anhydrous environment that reduces the interactions required for these components to initiate emulsification.

[0066] In some embodiments, a pharmaceutical composition disclosed herein can include 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, a pharmaceutical composition disclosed herein can comprise one or more glycerolipids in an amount of, for example, 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 can contain one or more glycerolipids in an amount of, for example, 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.

[0067] In some embodiments, the pharmaceutical compositions disclosed herein can include one or more glycerolipids in amounts 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 55%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 9 ...%. 0% to about 60%, about 30% to about 70%, 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%.

[0068] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerides that are solid at 18°C, said one or more hard fats or glycerides that are solid at 18°C ​​comprising, consisting essentially of, or consisting of: saturated C 10 -C 18 A mixture of triglycerides, saturated C 10 -C 20 A mixture of triglycerides, saturated C 10 -C 22 A mixture of triglycerides, saturated C 10 -C 24 A mixture of triglycerides, saturated C 12 -C 18 A mixture of triglycerides, saturated C 12 -C 20 A mixture of triglycerides, saturated C 12 -C 22 A mixture of triglycerides, saturated C 12 -C 24 A mixture of triglycerides, saturated C 14 -C 18 A mixture of triglycerides, saturated C 14 -C 20 A mixture of triglycerides, saturated C 14 -C 22 A mixture of triglycerides, saturated C 14 -C 24 A mixture of triglycerides, saturated C 16 -C 18 A mixture of triglycerides, saturated C 16 -C 20 A mixture of triglycerides, saturated C 16 -C 22 A mixture of triglycerides, saturated C 16 -C 24 A mixture of triglycerides, saturated C 18 -C 20 A mixture of triglycerides, saturated C 18 -C 22 A mixture of triglycerides, saturated C 18 -C 24 A mixture of triglycerides, saturated C 20 -C 22 A mixture of triglycerides or saturated C 22 -C 24 A mixture of triglycerides.

[0069] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerides that are solid at 18°C, said one or more hard fats or glycerides that are solid at 18°C ​​comprising, consisting essentially of, or consisting of: unsaturated C 10 -C 18 A mixture of triglycerides, unsaturated C 10 -C 20 A mixture of triglycerides, unsaturated C 10 -C 22 A mixture of triglycerides, unsaturated C 10 -C 24 A mixture of triglycerides, unsaturated C 12 -C 18 A mixture of triglycerides, unsaturated C 12 -C 20 A mixture of triglycerides, unsaturated C 12 -C 22 A mixture of triglycerides, unsaturated C 12 -C 24 A mixture of triglycerides, unsaturated C 14 -C 18 A mixture of triglycerides, unsaturated C 14 -C 20 A mixture of triglycerides, unsaturated C 14 -C 22 A mixture of triglycerides, unsaturated C 14 -C 24 A mixture of triglycerides, unsaturated C 16 -C 18 A mixture of triglycerides, unsaturated C 16 -C 20 A mixture of triglycerides, unsaturated C 16 -C 22 A mixture of triglycerides, unsaturated C 16 -C 24 A mixture of triglycerides, unsaturated C 18 -C 20 A mixture of triglycerides, unsaturated C 18 -C 22 A mixture of triglycerides, unsaturated C 18 -C 24 A mixture of triglycerides, unsaturated C 20 -C 22 A mixture of triglycerides or unsaturated C 22 -C 24 A mixture of triglycerides.

[0070] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerides that are solid at 18°C, said one or more hard fats or glycerides that are solid at 18°C ​​comprising, consisting essentially of, or consisting of: saturated and unsaturated C 10 -C 18 A mixture of triglycerides, saturated and unsaturated C 10 -C 20 A mixture of triglycerides, saturated and unsaturated C 10 -C 22 A mixture of triglycerides, saturated and unsaturated C 10 -C 24 A mixture of triglycerides, saturated and unsaturated C 12 -C 18 A mixture of triglycerides, saturated and unsaturated C 12 -C 20 A mixture of triglycerides, saturated and unsaturated C 12 -C 22 A mixture of triglycerides, saturated and unsaturated C 12 -C 24 A mixture of triglycerides, saturated and unsaturated C 14 -C 18 A mixture of triglycerides, saturated and unsaturated C 14 -C 20 A mixture of triglycerides, saturated and unsaturated C 14 -C 22 A mixture of triglycerides, saturated and unsaturated C 14 -C 24 A mixture of triglycerides, saturated and unsaturated C 16 -C 18 A mixture of triglycerides, saturated and unsaturated C 16 -C 20 A mixture of triglycerides, saturated and unsaturated C 16 -C 22 A mixture of triglycerides, saturated and unsaturated C 16 -C 24 A mixture of triglycerides, saturated and unsaturated C 18 -C 20 A mixture of triglycerides, saturated and unsaturated C 18 -C 22 A mixture of triglycerides, saturated and unsaturated C 18 -C 24 A mixture of triglycerides, saturated and unsaturated C 20 -C 22A mixture of triglycerides or saturated and unsaturated C 22 -C 24 A mixture of triglycerides.

[0071] 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 having a melting point of, for example, 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 ​​comprising, consisting essentially of, or consisting of a mixture of triglycerides having a melting point of, for example, 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 ​​comprising, consisting essentially of, or consisting of a mixture of triglycerides having a melting point of, for example, 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.

[0072] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more hard fats or glycerides that are solid at 18°C ​​comprising, consisting essentially of, or consisting of: having a temperature of, for example, 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 ℃ to about 37℃, about 28℃ to about 38℃, about 28℃ to about 39℃, about 28℃ to about 40℃, about 28℃ to about 41℃, about 28℃ to about 42℃, about 28℃ to about 43℃, about 28℃ to about 44℃, about 28℃ to about 45℃, about 28℃ to about 46℃, about 28℃ to about 47℃, about 28℃ to about 48℃, about 28℃ to about 49℃, about 28℃ to about 50℃, about 30℃ to about 37℃, about 30℃ to about 38℃, about 30℃ to about 39℃, about 30℃ to about 40℃, about 30℃ to about 41℃, about 30℃ to about 42℃, about 30℃ to about 43℃, about 30℃ to about 44℃, about 30℃ to about 45℃, about 30℃ to about 46℃ ℃, about 30℃ to about 47℃, about 30℃ to about 48℃, about 30℃ to about 49℃, about 30℃ to about 50℃, about 32℃ to about 44℃, about 32℃ to about 45℃, about 32℃ to about 46℃, about 32℃ to about 47℃, about 32℃ to about 48℃, about 32℃ to about 49℃, about 32℃ to about 50℃, about 34℃ to about 44℃, about 34℃ to about 45℃, about 34℃ to about 46℃, about 34℃ to about 47℃, about 34℃ to about 48℃, about 34℃ to about 49℃, about 34℃ to about 50℃, about 36℃ to about 44℃, about 36℃ to about 45℃, about 36℃ to about 46℃, about 36℃ to about 47℃, about 36℃ to about 48℃, about 36℃ to mixtures of triglycerides having a melting point of 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 49°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.

[0073] In some embodiments, the pharmaceutical compositions disclosed herein can comprise one or more hard fats or glycerides that are solid at 18°C, wherein the one or more hard fats or glycerides that are solid at 18°C ​​comprise, consist essentially of, or consist 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, wherein the one or more hard fats or glycerolipids that are solid at 18°C ​​comprise, consist essentially of, or consist of a mixture of triglycerides in an amount of, for example, 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, wherein the one or more hard fats or glycerolipids that are solid at 18°C ​​comprise, consist essentially of, or consist of a mixture of triglycerides in an amount of, for example, 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.

[0074] In some embodiments, the pharmaceutical compositions disclosed herein can comprise one or more hard fats or glycerides that are solid at 18° C. comprising, consisting essentially of, or consisting of, 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 ... 5% 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 2 5% 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 or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70%, or about 65% to about 70% of the mixture of triglycerides.

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

[0076] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, said one or more liquid fats or glycerolipids that are liquid at 18°C ​​comprising, consisting essentially of, or consisting of: saturated C 10 -C 18 Monoglyceride, C 10 -C 18 Diacylglycerol and C 10 -C 18 A mixture of triglycerides, saturated C 10 -C 20 Monoglyceride, C 10 -C 20 Diacylglycerol and C 10 -C 20 A mixture of triglycerides, saturated C 10 -C 22 Monoglyceride, C 10 -C 22 Diacylglycerol and C 10 -C 22 A mixture of triglycerides, saturated C 10 -C 24Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 A mixture of triglycerides, saturated C 12 -C 18 Monoglyceride, C 12 -C 18 Diacylglycerol and C 12 -C 18 A mixture of triglycerides, saturated C 12 -C 20 Monoglyceride, C 12 -C 20 Diacylglycerol and C 12 -C 20 A mixture of triglycerides, saturated C 12 -C 22 Monoglyceride, C 12 -C 22 Diacylglycerol and C 12 -C 22 A mixture of triglycerides, saturated C 12 -C 24 Monoglyceride, C 12 -C 24 Diacylglycerol and C 12 -C 24 A mixture of triglycerides, saturated C 14 -C 18 Monoglyceride, C 14 -C 18 Diacylglycerol and C 14 -C 18 A mixture of triglycerides, saturated C 14 -C 20 Monoglyceride, C 14 -C 20 Diacylglycerol and C 14 -C 20 A mixture of triglycerides, saturated C 14 -C 22 Monoglyceride, C 14 -C 22 Diacylglycerol and C 14 -C 22 A mixture of triglycerides, saturated C 14 -C 24 Monoglyceride, C 14 -C 24 Diacylglycerol and C 14 -C 24 A mixture of triglycerides, saturated C 16 -C 18 Monoglyceride, C 16-C 18 Diacylglycerol and C 16 -C 18 A mixture of triglycerides, saturated C 16 -C 20 Monoglyceride, C 16 -C 20 Diacylglycerol and C 16 -C 20 A mixture of triglycerides, saturated C 16 -C 22 Monoglyceride, C 16 -C 22 Diacylglycerol and C 16 -C 22 A mixture of triglycerides, saturated C 16 -C 24 Monoglyceride, C 16 -C 24 Diacylglycerol and C 16 -C 24 A mixture of triglycerides, saturated C 18 -C 20 Monoglyceride, C 18 -C 20 Diacylglycerol and C 18 -C 20 A mixture of triglycerides, saturated C 18 -C 22 Monoglyceride, C 18 -C 22 Diacylglycerol and C 18 -C 22 A mixture of triglycerides, saturated C 18 -C 24 Monoglyceride, C 18 -C 24 Diacylglycerol and C 18 -C 24 A mixture of triglycerides, saturated C 20 -C 22 Monoglyceride, C 20 -C 22 Diacylglycerol and C 20 -C 22 A mixture of triglycerides, or saturated C 22 -C 24 Monoglyceride, C 22 -C 24 Diacylglycerol and C 22 -C 24 A mixture of triglycerides.

[0077] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, said one or more liquid fats or glycerolipids that are liquid at 18°C ​​comprising, consisting essentially of, or consisting of: saturated and unsaturated C 10 -C 18 Monoglyceride, C 10 -C 18 Diacylglycerol and C 10 -C 18 A mixture of triglycerides, saturated and unsaturated C 10 -C 20 Monoglyceride, C 10 -C 20 Diacylglycerol and C 10 -C 20 A mixture of triglycerides, saturated and unsaturated C 10 -C 22 Monoglyceride, C 10 -C 22 Diacylglycerol and C 10 -C 22 A mixture of triglycerides, saturated and unsaturated C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 A mixture of triglycerides, saturated and unsaturated C 12 -C 18 Monoglyceride, C 12 -C 18 Diacylglycerol and C 12 -C 18 A mixture of triglycerides, saturated and unsaturated C 12 -C 20 Monoglyceride, C 12 -C 20 Diacylglycerol and C 12 -C 20 A mixture of triglycerides, saturated and unsaturated C 12 -C 22 Monoglyceride, C 12 -C 22 Diacylglycerol and C 12 -C 22 A mixture of triglycerides, saturated and unsaturated C 12 -C 24 Monoglyceride, C 12 -C 24 Diacylglycerol and C 12 -C 24A mixture of triglycerides, saturated and unsaturated C 14 -C 18 Monoglyceride, C 14 -C 18 Diacylglycerol and C 14 -C 18 A mixture of triglycerides, saturated and unsaturated C 14 -C 20 Monoglyceride, C 14 -C 20 Diacylglycerol and C 14 -C 20 A mixture of triglycerides, saturated and unsaturated C 14 -C 22 Monoglyceride, C 14 -C 22 Diacylglycerol and C 14 -C 22 A mixture of triglycerides, saturated and unsaturated C 14 -C 24 Monoglyceride, C 14 -C 24 Diacylglycerol and C 14 -C 24 A mixture of triglycerides, saturated and unsaturated C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 A mixture of triglycerides, saturated and unsaturated C 16 -C 20 Monoglyceride, C 16 -C 20 Diacylglycerol and C 16 -C 20 A mixture of triglycerides, saturated and unsaturated C 16 -C 22 Monoglyceride, C 16 -C 22 Diacylglycerol and C 16 -C 22 A mixture of triglycerides, saturated and unsaturated C 16 -C 24 Monoglyceride, C 16 -C 24 Diacylglycerol and C 16 -C 24 A mixture of triglycerides, saturated and unsaturated C 18 -C 20 Monoglyceride, C 18 -C 20 Diacylglycerol and C18 -C 20 A mixture of triglycerides, saturated and unsaturated C 18 -C 22 Monoglyceride, C 18 -C 22 Diacylglycerol and C 18 -C 22 A mixture of triglycerides, saturated and unsaturated C 18 -C 24 Monoglyceride, C 18 -C 24 Diacylglycerol and C 18 -C 24 A mixture of triglycerides, saturated and unsaturated C 20 -C 22 Monoglyceride, C 20 -C 22 Diacylglycerol and C 20 -C 22 A mixture of triglycerides, or saturated and unsaturated C 22 -C 24 Monoglyceride, C 22 -C 24 Diacylglycerol and C 22 -C 24 A mixture of triglycerides.

[0078] 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 triglycerides having a melting point of, for example, 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 ​​comprising, consisting essentially of, or consisting of a mixture of mono-, di-, and triglycerides having a melting point between, for example, 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.

[0079] 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 monoglycerides, diglycerides, 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, the pharmaceutical compositions disclosed herein can comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of, 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 of one or more monoglycerides. 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, for example, at most 10% by weight, at most 15% by weight, at most 20% by weight, at most 25% by weight, at most 30% by weight, at most 35% by weight, at most 40% by weight, at most 45% by weight, at most 50% by weight, at most 55% by weight, at most 60% by weight, at most 65% by weight, at most 70% by weight, or at most 75% by weight of one or more monoglycerides.

[0080] In some embodiments, the pharmaceutical compositions disclosed herein can comprise one or more liquid fats or glycerolipids that are liquid at 18° C., the one or more liquid fats or glycerolipids that are liquid at 18° C. comprising, consisting essentially of, or consisting of, 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 30%, about 15% 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 30%, about 15% to about 35%, about 10 ... 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 4 0%, 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%, mixtures of mono-, di-, and / or triglycerides in amounts of 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 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%.

[0081] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, wherein the one or more liquid fats or glycerolipids that are liquid at 18°C ​​comprise, consist essentially of, or consist of one or more monoglycerides. Monoglycerides include, but are not limited to, monomyristolein, monopalmitolein, glycerol monosapienate, monoolein, glycerol monoelaidate, glycerol monovaccenate, glycerol monolinoleate, glycerol monolinolelaidate, glycerol monolinolenate, glycerol monostearidonate, glycerol monoeicosenoate, glycerol monoomeadate, glycerol monoarachidonate, glycerol monoeicosapentaenoate, glycerol monoerucate, glycerol monodocosahexaenoate, and glycerol monooctadecenoate. monodocosahexaenoate) and glycerol mononervonate (glycerolmononervonate).

[0082] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, said one or more liquid fats or glycerolipids that are liquid at 18°C ​​comprising, consisting essentially of, or consisting of: unsaturated C 10 -C 18 Monoglycerides, unsaturated C 10 -C 20 Monoglycerides, unsaturated C 10 -C 22 Monoglycerides, unsaturated C 10 -C 24 Monoglycerides, unsaturated C 12 -C 18 Monoglycerides, unsaturated C 12 -C 20 Monoglycerides, unsaturated C12 -C 22 Monoglycerides, unsaturated C 12 -C 24 Monoglycerides, unsaturated C 14 -C 18 Monoglycerides, unsaturated C 14 -C 20 Monoglycerides, unsaturated C 14 -C 22 Monoglycerides, unsaturated C 14 -C 24 Monoglycerides, unsaturated C 16 -C 18 Monoglycerides, unsaturated C 16 -C 20 Monoglycerides, unsaturated C 16 -C 22 Monoglycerides, unsaturated C 16 -C 24 Monoglycerides, unsaturated C 18 -C 20 Monoglycerides, unsaturated C 18 -C 22 Monoglycerides, unsaturated C 18 -C 24 Monoglycerides, unsaturated C 20 -C 22 Monoglycerides or unsaturated C 22 -C 24 Monoglycerides.

[0083] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, said one or more liquid fats or glycerolipids that are liquid at 18°C ​​comprising, consisting essentially of, or consisting of: saturated C 10 -C 18 Monoglycerides, saturated C 10 -C 20 Monoglycerides, saturated C 10 -C 22 Monoglycerides, saturated C 10 -C 24 Monoglycerides, saturated C 12 -C 18 Monoglycerides, saturated C 12 -C 20 Monoglycerides, saturated C 12 -C 22 Monoglycerides, saturated C 12 -C 24 Monoglycerides, saturated C 14 -C18 Monoglycerides, saturated C 14 -C 20 Monoglycerides, saturated C 14 -C 22 Monoglycerides, saturated C 14 -C 24 Monoglycerides, saturated C 16 -C 18 Monoglycerides, saturated C 16 -C 20 Monoglycerides, saturated C 16 -C 22 Monoglycerides, saturated C 16 -C 24 Monoglycerides, saturated C 18 -C 20 Monoglycerides, saturated C 18 -C 22 Monoglycerides, saturated C 18 -C 24 Monoglycerides, saturated C 20 -C 22 Monoglycerides or saturated C 22 -C 24 Monoglycerides.

[0084] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18°C, said one or more liquid fats or glycerolipids that are liquid at 18°C ​​comprising, consisting essentially of, or consisting of: saturated and unsaturated C 10 -C 18 A mixture of monoglycerides, saturated and unsaturated C 10 -C 20 A mixture of monoglycerides, saturated and unsaturated C 10 -C 22 A mixture of monoglycerides, saturated and unsaturated C 10 -C 24 A mixture of monoglycerides, saturated and unsaturated C 12 -C 18 A mixture of monoglycerides, saturated and unsaturated C 12 -C 20 A mixture of monoglycerides, saturated and unsaturated C 12 -C 22 A mixture of monoglycerides, saturated and unsaturated C 12 -C 24 A mixture of monoglycerides, saturated and unsaturated C 14 -C 18A mixture of monoglycerides, saturated and unsaturated C 14 -C 20 A mixture of monoglycerides, saturated and unsaturated C 14 -C 22 A mixture of monoglycerides, saturated and unsaturated C 14 -C 24 A mixture of monoglycerides, saturated and unsaturated C 16 -C 18 A mixture of monoglycerides, saturated and unsaturated C 16 -C 20 A mixture of monoglycerides, saturated and unsaturated C 16 -C 22 A mixture of monoglycerides, saturated and unsaturated C 16 -C 24 A mixture of monoglycerides, saturated and unsaturated C 18 -C 20 A mixture of monoglycerides, saturated and unsaturated C 18 -C 22 A mixture of monoglycerides, saturated and unsaturated C 18 -C 24 A mixture of monoglycerides, saturated and unsaturated C 20 -C 22 A mixture of monoglycerides or saturated and unsaturated C 22 -C 24 A mixture of monoglycerides.

[0085] 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 monoglycerides having a melting point of, for example, 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 ​​comprising, consisting essentially of, or consisting of monoglycerides having a melting point between, for example, 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.

[0086] 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, 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 of one or more monoglycerides. 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, for example, 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 of one or more monoglycerides. 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, for example, at most 10% by weight, at most 15% by weight, at most 20% by weight, at most 25% by weight, at most 30% by weight, at most 35% by weight, at most 40% by weight, at most 45% by weight, at most 50% by weight, at most 55% by weight, or at most 60% by weight of one or more monoglycerides.

[0087] In some embodiments, the pharmaceutical compositions disclosed herein can comprise one or more liquid fats or glycerolipids that are liquid at 18° C., the one or more liquid fats or glycerolipids that are liquid at 18° C. comprising, consisting essentially of, or consisting of, 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% by weight. 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% 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 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%. 5%, 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 45%, 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%, One or more monoglycerides in an amount of 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 40% 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%, about 55% to about 60%.

[0088] Commercially available hard fats or glycerides that are solid at 18°C ​​include, but are not limited to, cocoa butter, saturated C 10 -C 18 A mixture of triglycerides ( 33 / 01), saturated C with a melting point of about 39°C 10 -C 18 A mixture of triglycerides ( 39 / 01) and saturated C with a melting point of about 43°C 10 -C 18 A mixture of triglycerides ( 43 / 01), commercially available liquid fats or glycerides that are liquid at 18°C ​​include, but are not limited to, hydrolyzed corn oil containing monolinoleylglycerol (MAISINE TM 35-1, MAISINETM In some embodiments, hydrolyzed corn oil (MAISINE TM 35-1, MAISINE TM CC) comprises about 32% to 52% monoglycerides (including monolinolein), about 40% to 50% diglycerides, and about 5% to 30% triglycerides.

[0089] The pharmaceutical compositions disclosed herein comprise any ratio of hard fats or glycerolipids that are solid at 18° C. to liquid fats or glycerolipids that are 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 fats or glycerolipids that are solid at 18° C. to liquid fats or glycerolipids that are 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 fats or glycerides that are solid at 18°C ​​to liquid fats or glycerides that are liquid at 18°C, e.g., from about 5:1 to about 4:1, from about 5:1 to about 3:1, from about 5:1 to about 2:1, from about 5:1 to about 1:1, from about 4:1 to about 3:1, from about 4:1 to about 2:1, from about 4:1 to about 1:1, from about 3:1 to about 2:1, from about 3:1 to about 1:1, or from about 2:1 to about 1:1.

[0090] In some embodiments, the pharmaceutical compositions disclosed herein comprise a ratio of hard fats or glycerolipids that are solid at 18° C. to liquid fats or glycerolipids that are liquid at 18° C., e.g., 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 fats or glycerolipids that are solid at 18° C. to liquid fats or glycerolipids that are liquid at 18° C., e.g., 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.

[0091] Digestive enhancers

[0092] The pharmaceutical compositions disclosed herein may include one or more digestion enhancers. The main purpose of one or more digestion enhancers is to enhance the solubility of the fibrates disclosed herein in a glycerolipid mixture; enhance the absorption of the fibrates disclosed herein, thereby improving the pharmacokinetics of the compound; and / or improve availability and promote the selected biodistribution of the fibrates disclosed herein, thereby improving the pharmacodynamics of the compound. These improved properties are achieved by one or more digestion enhancers by producing a lipid pre-digestion preparation of the fibrates disclosed herein, which promotes and enhances the processing of one or more glycerolipids disclosed herein when the pharmaceutical composition disclosed herein enters the duodenal region of the small intestine. Such glycerolipid processing enables the one or more fibrates contained in the pharmaceutical composition to be absorbed by the intestinal epithelial cells together with the digested glycerolipids, and subsequently processed and transported to the lymphatic system. In some embodiments, the disclosed pharmaceutical composition includes one or more digestion enhancers, and the one or more digestion enhancers include one or more bile acids. In some embodiments, the disclosed pharmaceutical composition includes one or more digestion enhancers, and the one or more digestion enhancers include bile acids. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancing agents, the one or more digestion enhancing agents including one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers, the one or more digestion enhancers comprising one or more C 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers, the one or more digestion enhancers comprising oleic acid, stearic acid, or linoleic acid. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers, the one or more digestion enhancers comprising one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers, the one or more digestion enhancers comprising one or more C 14 -C 20 Free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers including sodium oleate, sodium stearate, and / or sodium linoleate.

[0093] In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancing agents comprising 1) one or more bile acids disclosed herein; and 2) one or more C 14 -C24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers, the one or more digestion enhancers comprising 1) bile acid disclosed herein; and 2) one or more C 14 -C 20 Free fatty acids. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancing agents including 1) a bile acid disclosed herein; and 2) oleic acid, stearic acid, or linoleic acid.

[0094] In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancing agents comprising 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 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers, the one or more digestion enhancers comprising 1) bile acid disclosed herein; 2) one or more C 14 -C 20 Free fatty acids; and 3) one or more C 14 -C 20 Free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers including 1) a bile acid disclosed herein; 2) oleic acid, stearic acid, and / or linoleic acid; and 3) sodium oleate, sodium stearate, and / or sodium linoleate.

[0095] In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion-enhancing agents comprising 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 digestion-enhancing agents comprising 1) bile acids disclosed herein; and 2) one or more phospholipids disclosed herein.

[0096] In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancing agents, the one or more digestion enhancing agents comprising 1) one or more C disclosed herein; 14 -C 24Free fatty acids; and 2) one or more phospholipids disclosed herein. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers comprising 1) one or more C 14 -C 20 In some embodiments, the pharmaceutical compositions disclosed herein comprise one or more digestion enhancers comprising 1) oleic acid, stearic acid, and / or linoleic acid; and 2) one or more phospholipids disclosed herein.

[0097] In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancing agents comprising 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 digestion enhancers, comprising 1) one or more bile acids disclosed herein; 2) one or more C 14 -C 20 In some embodiments, the pharmaceutical compositions disclosed herein comprise one or more digestion enhancers comprising 1) bile acid disclosed herein; 2) oleic acid, stearic acid, and / or linoleic acid; and 3) one or more phospholipids disclosed herein.

[0098] In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancing agents comprising 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 digestion enhancers comprising 1) bile acid disclosed herein; 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 digestion enhancers comprising 1) bile acid disclosed herein; 2) one or more phospholipids disclosed herein; and 3) C disclosed herein. 14 -C 20Sodium free fatty acids. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers including 1) bile acid disclosed herein; 2) one or more phospholipids disclosed herein; and 3) sodium oleate, sodium stearate, and / or sodium linoleate.

[0099] In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancing agents, the one or more digestion enhancing agents comprising 1) one or more C 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 digestion enhancers, the one or more digestion enhancers comprising 1) one or more C disclosed herein; 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 digestion enhancers comprising 1) oleic acid, stearic acid, and / or linoleic acid; 2) one or more phospholipids disclosed herein; and 3) one or more C 14 -C 20 Sodium free fatty acid surfactant. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers comprising 1) oleic acid, stearic acid, and / or linoleic acid; 2) one or more phospholipids disclosed herein; and 3) sodium oleate, sodium stearate, and / or sodium linoleate.

[0100] In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancing agents comprising 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 digestion enhancers, the one or more digestion enhancers comprising 1) one or more bile acids disclosed herein; 2) one or more C 14 -C 20free 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 digestion enhancers, the one or more digestion enhancers comprising 1) bile acid disclosed herein; 2) oleic acid, stearic acid, and / or linoleic acid; 3) one or more phospholipids disclosed herein; and 4) one or more C 14 -C 20 Free fatty acid sodium surfactant. In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestion enhancers, the one or more digestion enhancers comprising 1) bile acid disclosed herein; 2) oleic acid, stearic acid, and / or linoleic acid; 3) one or more phospholipids disclosed herein; and 4) sodium oleate, sodium stearate, and / or sodium linoleate.

[0101] In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of one or more digestion enhancing agents in an amount of, for example, 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 can comprise, consist essentially of, or consist of, 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 of one or more digestion enhancing agents. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, e.g., at most 1% by weight, at most 2.5% by weight, at most 5% by weight, at most 7.5% by weight, at most 10% by weight, at most 12.5% ​​by weight, at most 15% by weight, at most 17.5% by weight, at most 20% by weight, at most 22.5% by weight, at most 25% by weight, at most 30% by weight, at most 35% by weight, at most 40% by weight, at most 45% by weight, at most 50% by weight, at most 55% by weight, at most 60% by weight, at most 65% by weight, at most 70% by weight, at most 75% by weight, or at most 80% by weight of one or more digestion enhancing agents.

[0102] In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist 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.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%, 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 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% 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 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%, about 65% to about 75%, about 65% to about 80%, about 70% to about 75%, about 70% to about 80%, or about 75% to about 80% by weight of one or more digestive enhancing agents.

[0103] Bile acids

[0104] The pharmaceutical compositions disclosed herein may comprise one or more bile acids. The primary purpose of bile acids is to enhance the solubility of the fibrates disclosed herein in a glycerolipid mixture, enhance the absorption of the fibrates disclosed herein, thereby improving the pharmacokinetics of the compound, and / or improve the availability and promote the selected biodistribution of the fibrates disclosed herein, thereby improving the pharmacodynamics of the compound. In addition, as disclosed in Example 2, bile acids disclosed herein improve the absorption of fibrates disclosed herein in one or more glycerolipids disclosed herein and / or one or more free C 14-24 Solubility in fatty acids. When the dissolved pharmaceutical composition is cooled to room temperature (18 ° C to 20 ° C), bile acids achieve improved solubility properties by preventing fibrates from recrystallizing during solidification. The improved pharmacokinetic properties are achieved by: bile acids decompose the lipid components of the pharmaceutical composition disclosed herein into smaller lipid structures that simulate emulsion droplets via its surfactant properties, thereby promoting the emulsification process. "Emulsion droplets" recruit colipase and create a larger surface area, and pancreatic lipase can digest the stearic glycerides present therein, ultimately enhancing intestinal epithelial cell absorption and subsequent chylomicron formation. Bile acids participate in the signal transduction that initiates chylomicron formation. Therefore, including bile acids in lipid formulations will maximize the production of this signal transduction pathway and chylomicrons. As a result, the improved pharmacodynamic properties provided by bile acids are produced by: increasing the availability of fibrates by increasing their content in chylomicrons before entering the circulatory system, and subsequently promoting the delivery of fibrates to compartments such as the brain through membranes such as the blood-brain barrier and the choroid plexus.

[0105] Bile acids, amphiphilic molecules with an HLB greater than 12, have a specific chemical structure that is different from ordinary aliphatic surfactants due to the presence of a large, rigid and flat hydrophobic portion of a steroid core carrying 2-4 hydroxyl groups. Specifically, bile acids contain the following basic components: (1) 4 rings, (2) 5-carbon / 8-carbon side chains ending in carboxylic acid, and (3) many hydroxyl groups (the position / number of which varies in various salts). Based on the distance between the rings and the side chains with -COOH groups, these rings are given the letters A, B, C and D, with the D ring being the farthest away (and 1C smaller than the other rings), as discussed below. The β hydroxyl groups face up / outward, the α groups face down, and each bile acid has a 3-hydroxyl group derived from its cholesterol precursor. The chemical structure of bile salts causes this emulsification approach to be useful according to the teachings of the present disclosure, and therefore, synthetic surfactants will not work.

[0106] Examples of bile acids include, but are not limited to, chenodeoxycholic acid, cholic acid, dafachronic acid, deoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, lithocholic acid, taurochenodeoxycholic acid, taurocholic acid, and any stereoisomers thereof. Cholic acid and chenodeoxycholic acid are referred to as primary bile acids, while deoxycholic acid (which is converted from cholic acid) and lithocholic acid (which is converted from chenodeoxycholic acid) are referred to as 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 the bile salts found in bile.

[0107] There is a direct correlation between the amount of bile acid present in the pharmaceutical composition disclosed herein and the properties of the observed improvement. Therefore, the more bile acid present in the pharmaceutical composition disclosed herein, the greater the improvement in solubility, absorption and availability of the therapeutic composition. In addition, the upper limit of the bile acid contained in the pharmaceutical composition disclosed herein is not limited to the dissolution point of the bile acid. Therefore, the pharmaceutical composition disclosed herein can include a supersaturated amount of bile acid. Therefore, the upper limit of the bile acid that can be included in the pharmaceutical composition disclosed herein is its critical micelle concentration (CMC). In addition to the improved properties mentioned above, another advantage of the supersaturated amount of bile acid is the formation of the resulting nanoparticles of crystalline bile acid in the pharmaceutical composition disclosed herein. Without being limited by a theory, bile acid nanoparticles can be used as a reservoir that dissolves and forms bile salts when exposed to the alkaline environment of the small intestine, which in turn further enhances the emulsification process of the pharmaceutical composition disclosed herein.

[0108] The amount of bile acid that can be used in the pharmaceutical compositions disclosed herein is an amount that is below its CMC. In some embodiments, the amount of bile acid that can be used in the pharmaceutical compositions disclosed herein is an amount that is below its CMC and is supersaturated. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist 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 of one or more bile acids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, 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 of one or more bile acids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, 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 of one or more bile acids.

[0109] In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, for example, by weight, 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%. 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% One or more bile acids in an amount 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%, 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%.

[0110] In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of, e.g., one or more bile acids at a concentration of 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, or at most 5 mM. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, e.g., one or more bile acids at a concentration of 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.

[0111] C 14-24 fatty acid

[0112] The pharmaceutical compositions disclosed herein may comprise one or more free C 14-24 Fatty acids. Fatty acids contain carboxylic acids with long, unbranched hydrocarbon chains that may be saturated or unsaturated, and are hydrophobic molecules with an HLB of less than 4. Free C 14-24 The main purpose of the fatty acids is to enhance 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. 14-24 The properties of fatty acids as solvents that promote the solubility of the fibrates disclosed herein, thus promoting the solubility of the fibrates through free C 14-24 Improved solubility properties are achieved by: free C 14-24 Fatty acids mimic the lipid digestion products of triglycerides, namely free fatty acids, by promoting and increasing the formation of micelles through the breakdown of larger emulsion droplets. 14-24 Fatty acids increase the uptake of micelles containing one or more fibrates into intestinal epithelial cells. In addition, as disclosed in Example 2, the free C 14-24 Fatty acids improve the solubility of the bile salts disclosed herein.

[0113] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more free C 14-24 Fatty acids, the one or more free C 14-24Fatty acids comprising or consisting essentially of or consisting of: 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 In some embodiments, the pharmaceutical compositions disclosed herein may include one or more free C 14-24 Fatty acids, the one or more free C 14-24 Fatty acids comprising or consisting essentially of or consisting of: ω-3 unsaturated free C 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 -C 22 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 -C22 fatty acid.

[0114] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more free C 14-24 Fatty acids, the one or more free C 14-24 Fatty acids comprise or consist essentially of or consist of: 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 fatty acid.

[0115] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more free C 14-24 Fatty acids, the one or more free C 14-24 Fatty acids comprise or consist essentially of or consist of: saturated and unsaturated free C 14 -C 16 A mixture of fatty acids, saturated and unsaturated free C 14 -C 18 A mixture of fatty acids, saturated and unsaturated free C 14 -C 20 A mixture of fatty acids, saturated and unsaturated free C 14 -C 22 A mixture of fatty acids, saturated and unsaturated free C14 -C 24 A mixture of fatty acids, saturated and unsaturated free C 16 -C 18 A mixture of fatty acids, saturated and unsaturated free C 16 -C 20 A mixture of fatty acids, saturated and unsaturated free C 16 -C 22 A mixture of fatty acids, saturated and unsaturated free C 16 -C 24 A mixture of fatty acids, saturated and unsaturated free C 18 -C 20 A mixture of fatty acids, saturated and unsaturated free C 18 -C 22 A mixture of fatty acids, saturated and unsaturated free C 18 -C 24 A mixture of fatty acids, saturated and unsaturated free C 20 -C 22 A mixture of fatty acids or saturated and unsaturated free C 22 -C 24 A mixture of fatty acids.

[0116] Free C 14-24Non-limiting examples of fatty acids include palmitic acid (hexadecanoic acid), palmitolinic acid, palmitidonic acid, palmitovaccenic acid, palmitoleic acid, cis-6-hexadecenoic acid (sapienic acid), 4-hexadecenoic acid, stearic acid (octadecenoic acid), α-linolenic acid, stearidonic acid, α-eleostearic acid, β-eleostearic acid, punicic acid, 7,10,13-octadecatrienoic acid, 12-octadecenoic acid, linoleic acid, trans-linoleic acid, gamma-linolenic acid, calendic acid, pinolenic acid, vaccinic acid, rumenic acid, oleic acid, elaidic acid, petroselinic acid, arachidic acid (eicosanoic acid), dihomo-α-linolenic acid, eicosatetraenoic acid, and trans-oleic acid. acid), eicosapentaenoic acid, 9,12,15-eicosatrienoic acid, beta-eicosatetraenoic acid, dihomo-linoleic acid, dihomo-gamma-linolenic acid, arachidonic acid, paullinic acid, 7,10,13-eicosatrienoic acid, gondoic acid, 8,11-eicosadienoic acid, meadic acid, cis-9-eicosenoic acid (gadoleic acid), 8-eicosenoic acid, behenic acid (docosanoic acid), clupanodonic acid, docosahexaenoic acid, adrenic acid, all-cis-4,7,10,13,16-docosapentaenoic 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 neuraminic acid.

[0117] In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, for example, 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 of one or more free C 14-24Fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist 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 of one or more free C 14-24 Fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, for example, at most 1% by weight, at most 2.5% by weight, at most 5% by weight, at most 7.5% by weight, at most 10% by weight, at most 12.5% ​​by weight, at most 15% by weight, at most 17.5% by weight, at most 20% by weight, at most 22.5% by weight, at most 25% by weight, at most 30% by weight, at most 35% by weight, at most 40% by weight, at most 50% by weight, at most 60% by weight, at most 70% by weight, or at most 75% by weight of one or more free C 14-24 fatty acid.

[0118] In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist 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 1% to about 25% by weight, about 2.5% to about 30% 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 1% to about 2 ...1% to about 20% by weight, about 1% to about 25% by weight, about 1% to about 20% by weight, about 1% to about 25% by weight, about 1% to about 20% by weight, about 1% to From about 5% to about 10% by weight, from about 5% to about 15% by weight, from about 5% to about 20% by weight, from about 5% to about 25% by weight, from about 5% to about 30% by weight, from about 10% to about 15% by weight, from about 10% to about 20% by weight, from about 10% to about 25% by weight, from about 10% to about 30% by weight, from about 10% to about 40% by weight, from about 10% to about 45% by weight, from about 10% to about 50% by weight, from about 10% to about 60% by weight, from about 10% to about 70% by weight, from about 15% to about 20% by weight, from about 15% to about 25% by weight , about 15% to about 30% by weight, about 15% to about 40% by weight, about 15% to about 45% by weight, about 15% to about 50% by weight, about 15% to about 60% by weight, about 15% to about 70% by weight, about 20% to about 25% by weight, about 20% to about 30% by weight, about 20% to about 40% by weight, about 20% to about 45% by weight, about 20% to about 50% by weight, about 20% to about 60% by weight, about 20% to about 70% by weight, about 30% to about 40% by weight, about 30% to about 50% by weight, about 30% to about 60% by weight, 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 14-24 fatty acid.

[0119] In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of, for example, one or more free C at a concentration of 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 Fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist 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 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 0.01 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 The present invention also provides one or more free C in a concentration of 0.05 mM to 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 1.5 mM to about 2 mM. 14-24 fatty acid.

[0120] phospholipids

[0121] Pharmaceutical compositions disclosed herein may include one or more phospholipids. Like bile acids disclosed herein, phospholipids disclosed herein decompose the lipid components of pharmaceutical compositions disclosed herein into smaller lipid structures that simulate emulsion droplets via their surfactant properties, thereby promoting the emulsification process. "Emulsion droplets" recruit colipase and produce larger surface areas, and pancreatic lipase can digest the stearic glycerides present therein. In addition, phospholipids disclosed herein, together with free fatty acid surfactants disclosed herein, promote the formation of micelles by associating with the lipid digestion products of triglycerides, and then enhancing the association of triglyceride digestion products with fatty acid transporters, thereby enhancing the absorption of lipid molecules and associated fibrates into intestinal epithelial cells.

[0122] The structure of phospholipids usually comprises the hydrophobic tail of one or more fatty acids and the hydrophilic head containing the phosphoric acid functional group, and is amphipathic in nature and has an HLB greater than 12.Phospholipids include but are not limited to phosphoglycerides and sphingomyelin.Phosphoglycerides have the general structure that comprises glycerol backbone, wherein two fatty acids are esterified to the first hydroxyl group and the second hydroxyl group of glycerol, and the phosphate group is esterified to the 3rd hydroxyl group of glycerol.Alcohol group is esterified to the phosphate group of phosphoglycerides.Phosphoglycerides always have two kinds of fatty acids, and usually one kind of fatty acid is saturated and another kind is unsaturated.Phosphoglycerides are usually classified according to the specific alcohol group present in the phosphate group, such as for example 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).

[0123] Although structurally different, sphingomyelin also has a polar head and two non-polar tails. Sphingomyelin has a general structure comprising a long-chain amino alcohol sphingosine backbone, wherein fatty acids form amide bonds with the amino groups of the sphingosine backbone, and the phosphate groups are esterified with the hydroxyl groups of the sphingosine backbone. Non-limiting examples of sphingomyelin include ceramide phosphoethanolamine (Cer-PE), ceramide phosphocholine (Cer-PC), and ceramide phosphoglycerol (Cer-PG).

[0124] In addition to its amphipathic properties, phospholipids can be zwitterionic phospholipids. Zwitterionic phospholipids are fully ionized molecules that contain equal numbers of positively charged functional groups and negatively charged functional groups and are electrically neutral. Non-limiting examples of zwitterionic phospholipids include phosphatidylethanolamine (PE), phosphatidylcholine (PC), ceramide phosphoethanolamine (Cer-PE) and ceramide phosphocholine (Cer-PC).

[0125] Phospholipids disclosed herein include lecithin. Lecithin is an amphiphilic mixture of glycerophospholipids. In some embodiments, lecithin comprises a mixture of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and phosphatidic acid. In some embodiments, lecithin comprises 19% to 21% phosphatidylcholine, 8% to 20% phosphatidylethanolamine, 20% to 21% phosphatidylinositol and 5% to 11% phospholipids comprising phosphatidylserine and phosphatidic acid.

[0126] In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist 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 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 one or more phospholipids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, 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 of one or more phospholipids. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, 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 of one or more phospholipids.

[0127] In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, for example, by weight, 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%. 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% The one or more phospholipids may be present in an amount of about 9.0%, about 4.0% 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%.

[0128] C 14-24 fatty acid surfactants

[0129] The pharmaceutical compositions disclosed herein may comprise one or more free C 14-24Fatty acid surfactant. Fatty acid surfactants contain carboxylic acid with a long, unbranched hydrocarbon chain that may be saturated or unsaturated and associated with an alkali metal, and are hydrophobic or amphiphilic molecules with an HLB greater than 12. Free C 14-24 The main purpose of the fatty acid surfactant is to enhance the solubility of the fibrates disclosed herein in the glycerolipid mixture and enhance the absorption of the fibrates disclosed herein, thereby improving the pharmacokinetics of the compound. The improved solubility properties are achieved by: free C 14-24 The fatty acid surfactant interacts with the sodium ions present on the fibrates through its carboxylic acid functional group, which neutralizes the charge and promotes the interaction of the compound with the hydrophobic glycolipid mixture. The improved absorption properties are achieved by: free C 14-24 Fatty acid surfactants mimic the lipid digestion products of triglycerides, namely free fatty acids, by promoting and increasing the formation of mixed micelles by breaking up larger emulsion droplets. 14-24 Fatty acid surfactants increase the uptake of micelles containing one or more fibrates into intestinal epithelial cells. 14-24 Fatty acid surfactants are free C2+ atoms associated with alkali metals such as, for example, lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr), or alkaline earth metals such as, for example, beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra). 14-24 fatty acid.

[0130] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more free C 14-24 Fatty acid surfactant, the one or more free C 14-24 The fatty acid surfactant comprises or consists essentially of or consists of: an unsaturated free C 14 -C 16 Fatty acid surfactants, unsaturated free C 14 -C 18 Fatty acid surfactants, unsaturated free C 14 -C 20 Fatty acid surfactants, unsaturated free C 14 -C 22 Fatty acid surfactants, unsaturated free C 14 -C 24 Fatty acid surfactants, unsaturated free C 16 -C 18 Fatty acid surfactants, unsaturated free C 16 -C 20Fatty acid surfactants, unsaturated free C 16 -C 22 Fatty acid surfactants, unsaturated free C 16 -C 24 Fatty acid surfactants, unsaturated free C 18 -C 20 Fatty acid surfactants, unsaturated free C 18 -C 22 Fatty acid surfactants, unsaturated free C 18 -C 24 Fatty acid surfactants, unsaturated free C 20 -C 22 Fatty acid surfactants or unsaturated free C 22 -C 24 Fatty acid surfactants. In some embodiments, the pharmaceutical compositions disclosed herein may include one or more free C 14-24 Fatty acid surfactant, the one or more free C 14-24 The fatty acid surfactant comprises, consists essentially of, or consists of: ω-3 unsaturated free C 18 -C 22 Fatty acid surfactants, ω-5 unsaturated free C 18 -C 22 Fatty acid surfactants, ω-6 unsaturated free C 18 -C 22 Fatty acid surfactants, 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 surfactants or ω-12 unsaturated free C 18 -C 22 Fatty acid surfactant.

[0131] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more free C 14-24 Fatty acid surfactant, the one or more free C 14-24 The fatty acid surfactant comprises, consists essentially of, or consists of: saturated free C 14 -C 16 Fatty acid surfactants, saturated free C 14-C 18 Fatty acid surfactants, saturated free C 14 -C 20 Fatty acid surfactants, saturated free C 14 -C 22 Fatty acid surfactants, saturated free C 14 -C 24 Fatty acid surfactants, saturated free C 16 -C 18 Fatty acid surfactants, saturated free C 16 -C 20 Fatty acid surfactants, saturated free C 16 -C 22 Fatty acid surfactants, saturated free C 16 -C 24 Fatty acid surfactants, saturated free C 18 -C 20 Fatty acid surfactants, saturated free C 18 -C 22 Fatty acid surfactants, saturated free C 18 -C 24 Fatty acid surfactants, saturated free C 20 -C 22 Fatty acid surfactants or saturated free C 22 -C 24 Fatty acid surfactant.

[0132] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more free C 14-24 Fatty acid surfactant, the one or more free C 14-24 The fatty acid surfactant comprises, consists essentially of, or consists of: saturated and unsaturated free C 14 -C 16 A mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 18 A mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 20 A mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 22 A mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 24 A mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 18 A mixture of fatty acid surfactants, saturated and unsaturated free C16 -C 20 A mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 22 A mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 24 A mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 20 A mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 22 A mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 24 A mixture of fatty acid surfactants, saturated and unsaturated free C 20 -C 22 A mixture of fatty acid surfactants or saturated and unsaturated free C 22 -C 24 A mixture of fatty acid surfactants.

[0133] Free C 14-24Non-limiting examples of fatty acid surfactants include sodium palmitate (sodium hexadecanoate), sodium palmitolenate, sodium palmitoid, sodium palm vaccenate, sodium palmitoleate, sodium cis-6-hexadecenoate, sodium 4-hexadecenoate, sodium stearate (sodium octadecenoate), sodium α-linolenate, sodium stearatetraenoate, sodium α-eleostearate, sodium β-eleostearate, sodium punicate, sodium 7,10,13-octadecatrienoate, sodium 12-octadecenoate, sodium linoleate, sodium trans-linoleate, sodium γ-linolenate, sodium calendulanate, sodium calendate), sodium pinolenate, sodium vaccinate, sodium rumenate, sodium oleate, sodium elaidate, sodium petroselinate, sodium arachidonic acid (sodium eicosanoate), sodium dihomo-α-linolenate, sodium eicosate, sodium eicosapentaenoate, sodium 9,12,15-eicosatrienoate, sodium β-eicosate, sodium dihomo-linoleate, sodium dihomo-γ-linolenate, sodium arachidonic acid, sodium eicosenoate, sodium 7,10,13-eicosatrienoate, sodium gondolate, sodium 8,11-eicosadienoate, sodium meadate, sodium gadoleate, sodium 8-eicosenoate, sodium behenate (sodium docosanoate), sodium oleate (sodium clupanodonate), sodium docosahexaenoate, sodium adrenate, sodium osbondate, sodium erucate, sodium lignocerate (sodium tetracosanoate), sodium 9,12,15,18,21-tetracosapentaenoate, sodium 6,9,12,15,18,21-tetracosahexaenoate, and sodium neuraminate.

[0134] One or more free C 14-24 The lower limit of the fatty acid surfactant is an amount sufficient to dissolve the fibrate and impart improved absorption properties thereto. The one or more free C 14-24 The upper limit of fatty acid surfactants is their micelle concentration (CMC).

[0135] One or more free C 14-24The amount of fatty acid surfactant is an amount below its CMC. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist 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 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 one or more free C 14-24 Fatty acid surfactants. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist 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 of one or more free C 14-24 Fatty acid surfactant. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, for example, 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 of one or more free C 14-24 Fatty acid surfactant.

[0136] In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, for example, by weight, 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%. 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% The present invention also provides one or more free C in an amount of about 9.0%, about 4.0% 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%. 14-24 Fatty acid surfactant.

[0137] In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of, for example, one or more free C at a concentration of at most 5 μM, at most 10 μM, at most 15 μM, at most 20 μM, at most 25 μM, at most 30 μM, or at most 35 μM. 14-24 Fatty acid surfactants. In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, for example, 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 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 1 μM to about 35 μM, about 1 μM to about The present invention also provides one or more free C in a concentration of 0 μM to about 15 μM, about 10 μM to about 20 μM, about 10 μM to about 25 μM, about 10 μM to about 30 μM, about 10 μM to about 35 μM, about 15 μM to about 20 μM, about 15 μM to about 25 μM, about 15 μM to about 30 μM, about 15 μM to 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 Fatty acid surfactant.

[0138] Curcumin

[0139] Aspects of this specification disclose, in part, curcumin. In some embodiments, pharmaceutical compositions disclosed herein may include curcumin. Curcumin is a phenolic pigment extracted from turmeric (Curcuma longa). Although curcumin is a pharmacologically bioactive molecule, it can promote gallbladder contraction, making the compound useful as a digestive enhancer disclosed herein. Gallbladder contraction is an important process in fat absorption and therefore provides important benefits: by breaking down larger emulsion droplets to increase the formation of mixed micelles, thereby increasing the uptake of micelles containing one or more fibrates into intestinal epithelial cells.

[0140] The amount of Curcumin that can be used 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 comprise, consist essentially of, or consist of Curcumin in an amount 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 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 comprise, consist essentially of, or consist of Curcumin in an amount of, 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 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 of, for example, 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.

[0141] In some embodiments, the pharmaceutical compositions disclosed herein can comprise, consist essentially of, or consist of, for example, by weight, 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 or about 9.0% to about 10.0%, about 4.0% 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%.

[0142] Diol polymer

[0143] Aspects of the present specification disclose, in part, diol polymers.In some embodiments, the pharmaceutical compositions disclosed herein can comprise one or more diol polymers.

[0144] The pharmaceutical compositions disclosed herein may comprise 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 can include a stabilizer in an amount of, 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% by weight.In other aspects of this embodiment, the pharmaceutical compositions disclosed herein can include a stabilizer in an amount 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 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%, about 2% to about 20% by weight, about 3% to about 5% by weight, about 3% to about 7% by weight, about 3% to about 10% by weight, about 3% to about 12% by weight, about 3% to about 15% by weight, about 3% to about 18% by weight, about 3% to about 20% by weight, about 4% to about 5% by weight, about 4% to about 7% by weight, about 4% to about 10% by weight, about 4% to about 12% by weight, about 4% to about 15% by weight, about 4% to about 18% by weight, about 4% to about 20% by weight, about 5% to about 7% by weight, about 5% to about 10% by weight, about 5% to about 12% by weight, about 5% to about 15% by weight, about 5% to about 18% by weight, about 5% to about 20% by weight, about 6% to about 7% by weight, about 6% to about 10% by weight, about 6% to about 12% by weight, about 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.

[0145] Stabilizer as disclosed herein is not a solvent, because it is used in a large amount of dissolving amount that does not cause solute.Therefore, the amount of the stabilizer used in the solid solution composition disclosed herein causes no more than 85% dissolving of fibrates disclosed herein.In the aspect of this embodiment, the amount of the stabilizer used in the solid solution composition disclosed herein causes no more than 80%, no more than 75%, no more than 70%, no more than 65%, no more than 60%, no more than 55%, no more than 50%, no more than 45%, no more than 40%, no more than 35%, no more than 30%, no more than 25%, no more than 20%, no more than 15%, no more than 10% or no more than 5% dissolving of fibrates disclosed herein.

[0146] In embodiments, glycol polymers can include pharmaceutically acceptable PEG polymers.PEG polymers, also referred to as polyethylene oxide (PEO) polymers or polyoxyethylene (POE) polymers, are prepared by the polymerization of ethylene oxide, and are commercially available in the wide range molecular weight from 100g / mol to 10,000,000g / mol. PEG polymers with low molecular weight are liquid or low melting point solids, and higher molecular weight PEG polymers are solids. In aspects of this embodiment, the PEG polymers used as stabilizers are liquid PEG polymers. In aspects of this embodiment, PEG polymers have, for example, no more than 100g / mol, no more than 200g / mol, no more than 300g / mol, no more than 400g / mol, no more than 500g / mol, no more than 600g / mol, no more than 700g / mol, no more than 800g / mol, no more than 900g / mol or no more than 1000g / mol molecular weight.

[0147] PEG polymers include, but are not limited to, PEG 100, PEG 200, PEG 300, PEG 400, PEG 500, PEG 600, PEG 700, PEG 800, PEG 900, PEG 1000, PEG 1100, PEG 1200, PEG 1300, PEG 1400, PEG 1500, PEG 1600, PEG 1700, PEG 1800, PEG 1900, PEG 2000, PEG 2100, PEG 2200, PEG 2300, PEG 2400, PEG 2500, PEG 2600, PEG 2700, PEG 2800, PEG 2900, PEG 3000, PEG 3250, PEG3350, PEG 3500, PEG 3750, PEG 4000, PEG 4250, PEG 4500, PEG 4750, PEG 5000, PEG 5500, PEG 6000, PEG 6500, PEG 7000, PEG 7500, PEG 8000, PEG 8500, PEG 9000, PEG 9500, PEG10,000, PEG 11,000, PEG 12,000, PEG 13,000, PEG 14,000, PEG 15,000, PEG 16,000, PEG 17,000, PEG 18,000, PEG 19,000 or PEG 20,000.

[0148] In another embodiment, the glycol polymer may comprise a pharmaceutically acceptable polypropylene glycol (PPG) polymer. PPG polymers, also known as polypropylene oxide (PPO) polymers or polyoxypropylene (POP) polymers, are prepared by the polymerization of propylene oxide and are commercially available in a wide range of molecular weights from 100 g / mol to 10,000,000 g / mol. PPG polymers with low molecular weight are liquids or low melting point solids, while PPG polymers with higher molecular weights are solids. In aspects of this embodiment, the PPG polymer used as a stabilizer is a liquid PPG polymer. In aspects of this embodiment, the PPG polymer has, for example, a molecular weight of no more than 100 g / mol, no more than 200 g / mol, no more than 300 g / mol, no more than 400 g / mol, no more than 500 g / mol, no more than 600 g / mol, no more than 700 g / mol, no more than 800 g / mol, no more than 900 g / mol, or no more than 1000 g / mol.

[0149] PPG polymers include but are not limited to PPG 100, PPG 200, PPG 300, PPG 400, PPG 500, PPG 600, PPG 700, PPG 800, PPG 900, PPG 1000, PPG 1100, PPG 1200, PPG 1300, PPG 1400, PPG1500, PPG 1600, PPG 1700, PPG 1800, PPG 1900, PPG 2000, PPG 2100, PPG 2200, PPG 2300, PPG 2400, PPG 2500, PPG 2600, PPG 2700, PPG 2800, PPG 2900, PPG 3000, PPG 3250, PPG3350, PPG 3500, PPG 3750, PPG 4000, PPG 4250, PPG 4500, PPG 4750, PPG 5000, PPG 5500, PPG 6000, PPG 6500, PPG 7000, PPG 7500, PPG 8000, PPG 8500, PPG 9000, PPG 9500, PPG10,000, PPG 11,000, PPG 12,000, PPG 13,000, PPG 14,000, PPG 15,000, PPG 16,000, PPG17,000, PPG 18,000, PPG 19,000 or PPG 20,000.

[0150] In some embodiments, the pharmaceutical compositions disclosed herein do not include a glycol polymer. In aspects of these embodiments, the pharmaceutical compositions disclosed herein do not include a PEG polymer. In other aspects of these embodiments, the pharmaceutical compositions disclosed herein do not include a PGG polymer. In yet other aspects of these embodiments, the pharmaceutical compositions disclosed herein do not include both a PEG polymer and a PGG polymer.

[0151] Release effect

[0152] In embodiments, a large amount of fibrates present in pharmaceutical compositions disclosed herein are delivered to or enter lipid digestion and / or absorption pathways. 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% fibrates present in pharmaceutical compositions disclosed herein are delivered to or enter lipid digestion and / or absorption pathways. 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% fibrates present in pharmaceutical compositions disclosed herein are delivered to or enter lipid digestion and / or absorption pathways. In yet other aspects of this embodiment, at most 10%, at most 20%, at most 30%, at most 40%, at most 50%, at most 60%, at most 70%, at most 80%, at most 90%, or at most 95% of the fibrate present in the pharmaceutical compositions disclosed herein is delivered to or enters the lipid digestion and / or absorption pathways.

[0153] In yet 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% 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 20% 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 90%, about 30% to about 100%, 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 100%, about 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 90%, about 50% to about 100%, about 60% to about 70%, about 60% to about 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% of the fibrate is delivered to or enters the lipid digestion and / or absorption pathway.

[0154] In an embodiment, a substantial amount of the fibrate present in a pharmaceutical composition disclosed herein is absorbed by the capillaries and enters directly into the bloodstream. In aspects of this embodiment, at most 1%, at most 5%, at most 10%, at most 20%, at most 30%, at most 40%, at most 50%, at most 60%, at most 70%, at most 80%, at most 90%, or at most 95% of the fibrate present in a pharmaceutical composition disclosed herein is absorbed by the capillaries and enters directly into the bloodstream. 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%, From about 10% to about 50%, from about 10% to about 60%, from about 10% to about 70%, from about 10% to about 80%, from about 10% to about 90%, from about 10% to about 95%, from about 20% to about 30%, from about 20% to about 40%, from about 20% to about 50%, from about 20% to about 60%, from about 20% to about 70%, from about 20% to about 80%, from about 20% to about 90%, from about 20% to about 95%, from 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%, 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 5 From 0% to about 80%, from about 50% to about 90%, from about 50% to about 95%, from about 60% to about 70%, from about 60% to about 80%, from about 60% to about 90%, from about 60% to about 95%, from about 70% to about 80%, from about 70% to about 90%, from about 70% to about 95%, from about 80% to about 90%, from about 80% to about 95%, or from about 90% to about 95% of the fibrate is absorbed by the capillaries and directly into the blood.

[0155] Preparation Procedure

[0156] The inclusion of one or more digestive enhancers into the one or more fibrates disclosed herein is applicable to any fibrate administered by a route of administration in which the compound is absorbed by the gastrointestinal tract, such as, for example, oral delivery. However, the formulation of the pharmaceutical compositions disclosed herein depends on the solubility of the fibrate in the 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 the one or more fibrates remain stably incorporated into the glycerolipid mixture.

[0157] In some embodiments, the selected fibrate can be formulated using 1) a glyceride comprising at least one liquid fat (a glyceride that is liquid at 18°C) and at least one hard fat (a glyceride that is solid at 18°C), and 2) one or more digestion-enhancing agents. In some embodiments, the one or more liquid fats and hard fats are first heated, and the one or more digestion-enhancing agents are dissolved in the glyceride mixture. After the digestion-enhancing agents are completely dissolved, and if appropriate, the temperature of the mixture can be adjusted, the selected fibrate is then dissolved in the heated mixture to incorporate the compound. In some embodiments, the one or more liquid fats are first heated, and the one or more digestion-enhancing agents are dissolved in the liquid fats. After the digestion-enhancing agents are completely dissolved, and if appropriate, the temperature of the mixture can be adjusted, the selected fibrate is then dissolved in the heated mixture to incorporate the compound. After the fibrate is completely dissolved, the one or more hard fats are then added to the heated mixture. In some embodiments, the one or more digestion-enhancing agents are first heated, and the selected fibrate is then dissolved in the heated mixture to incorporate the compound. After the fibrates are completely dissolved, and if appropriate, the temperature of the mixture can be adjusted, and then one or more liquid fats are added and mixed into the mixture. After the one or more liquid fats are completely dissolved, then one or more hard fats are added and mixed into the mixture. The initial heating step in all procedures is carried out at a temperature sufficient to dissolve one or more digestion enhancers and selected fibrates, and this temperature can be determined empirically based on the melting point of the selected component. Typically, this temperature range is from about 60°C to about 170°C. When one or more liquid fats and / or one or more hard fats are added to the mixture, any subsequent adjustment of heat is carried out at a temperature sufficient to melt the hard fat, and this temperature can be determined empirically based on the melting point of the hard fat used in the preparation. Typically, this temperature range is from about 40°C to about 60°C.

[0158] The mixture of this incorporation is then allowed to cool to room temperature, at which point stirring is stopped and the mixture is transferred to a suitable container where it will solidify. Once cooled, the stability of the pharmaceutical composition can optionally be tested by reheating the composition to a temperature sufficient to melt it. The reheating step is carried out at a temperature sufficient to melt the glycerolipid component, and this temperature can be determined empirically based on the melting point of the hard fat used in the preparation. Typically, this temperature range is 40°C to 50°C. The selection of one or more digestion enhancers is generally not a key component in this process, as bile acids, free fatty acids, phospholipids or free fatty acid surfactants can be used in any combination to achieve pharmaceutical compositions disclosed herein. As shown in Example 2, the preparation method all includes a complete dissolution phase, which undergoes nanocrystallization of some components when cooled, as shown in the XRPD spectrum.

[0159] Example 3 illustrates fibrates formulated according to this process. These examples also reveal two subgroups of formulations. In one subgroup, the presence of one or more digestion enhancers does not significantly enhance the solubility of the fibrate in the glycerolipid matrix. Instead, the presence of the digestion enhancer is used to improve the bioavailability of the fibrate.

[0160] Methods and uses

[0161] Aspects of this specification disclose, in part, a method for treating an individual suffering from chronic inflammation. In one embodiment, the method comprises the step of administering a pharmaceutical composition disclosed herein to an individual in need thereof, wherein administration reduces symptoms associated with chronic inflammation, thereby treating the individual. Other aspects of this specification disclose, in part, a method for treating an individual suffering from neuroinflammation. In one embodiment, the method comprises the step of administering a pharmaceutical composition disclosed herein to an individual in need thereof, wherein administration reduces symptoms associated with neuroinflammation, thereby treating the individual.

[0162] Aspects of the present specification disclose, in part, pharmaceutical compositions disclosed herein for use in treating chronic inflammation. Other aspects of the present specification disclose, in part, pharmaceutical compositions disclosed herein for use in treating neuroinflammation.

[0163] Aspects of this specification disclose, in part, the use of the pharmaceutical compositions disclosed herein for treating chronic inflammation. Other aspects of this specification disclose, in part, the use of the pharmaceutical compositions disclosed herein for treating neuroinflammation.

[0164] Since the pharmaceutical compositions disclosed herein rely on the digestive processes of the gastrointestinal tract, oral administration is the preferred route of administration.

[0165] Aspects of the present specification disclose, in part, treating an individual suffering from chronic inflammation and / or neuroinflammation. As used herein, the term "treating" refers to reducing or eliminating clinical symptoms of chronic inflammation and / or neuroinflammation in an individual; or delaying or preventing the onset of clinical symptoms of chronic inflammation and / or neuroinflammation in an individual. For example, the term "treating" can mean reducing the symptoms of a 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 ordinary 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 tissues or organs affected by the chronic inflammation and / or neuroinflammation. One skilled in the art will be aware of 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 treatment as disclosed herein.

[0166] Symptoms of chronic inflammation include, but are not limited to, edema, congestion, erythema, bruising, tenderness, stiffness, swelling, fever, chills, nasal congestion, a heavy head, breathing problems, fluid retention, blood clots, loss of appetite, increased heart rate, granuloma formation, fibrinous, purulent, non-viscous serous fluid, or ulcers and pain. The actual symptoms associated with chronic inflammation are well known and can be determined by one of ordinary skill 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 tissues or organs affected, and the associated disorder.

[0167] During the specific circumstances that occur in the body, such as when inflammation occurs on the epithelial surface or involves pus-forming bacteria, a specific pattern of chronic inflammation is seen. For example, granulomatous inflammation is an inflammation caused by the formation of granulomas caused by a limited but varying number of diseases, including but not limited to tuberculosis, leprosy, sarcoidosis and syphilis. Purulent inflammation is an inflammation that causes a large amount of pus, which is composed of neutrophils, dead cells and fluid. Infection with pus-forming bacteria such as staphylococci is a characteristic of this inflammation. Serous inflammation is an inflammation caused by a large amount of exudate of non-viscous serous fluid, usually produced by the mesothelial cells of the serosal membrane, but can be derived from plasma. Skin blisters illustrate this pattern of inflammation. Ulcerative inflammation is an inflammation caused by the necrotic loss of tissue from the epithelial surface, exposing the lower layer and forming an ulcer.

[0168] Chronic inflammatory symptoms can be associated with a large group of unrelated disorders, which are the basis of various diseases and disorders. The immune system is generally associated with chronic inflammatory disorders, showing both allergic reactions and some myopathies, and many of these immune system disorders result in abnormal inflammation. Non-immune diseases with a cause of disease origin in chronic inflammatory processes include cancer, atherosclerosis, and ischemic heart disease. Non-limiting examples of disorders that show chronic inflammation as symptoms include but are not limited to 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, celiac disease, cellulitis, cervicitis, cholangitis, cholecystitis, chorioamnionitis, chronic obstructive pulmonary disease (COPD), cirrhosis, colon inflammation, congestive heart failure, conjunctivitis, cyclophosphamide-induced cystitis, cystic fibrosis, cystitis, common cold, dacryoadenitis, dementia, dermatitis, dermatomyositis, diabetes, diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic ulcers, digestive system diseases, eczema, emphysema, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibromyalgia, fibrosis, fibrositis, gastritis, gastroenteritis, gingivitis, glomerulonephritis, glossitis, heart disease, heart valve dysfunction, hepatitis, hidradenitis suppurativa, Huntington's disease, hyperlipidemia Hyperemic pancreatitis, hypertension, ileitis, infection, inflammatory bowel disease, inflammatory cardiomegaly, 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, nonalcoholic steatohepatitis, obesity, omphalitis, oophoritis, orchitis, osteochondritis, osteopenia, osteomyelitis, osteoporosis, osteitis, otitis, pancreatitis, Parkinson's disease, mumps, pelvic inflammatory disease, pemphigus vulgaris, heart disease Pericarditis, peripheral neuropathy, peritonitis, pharyngitis, phlebitis, pleurisy, pneumonia, polycystic nephritis, proctitis, prostatitis, psoriasis, pulpitis, pyelonephritis, portal vein thrombosis, 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, trigoneitis, tuberculosis, tumors, urethritis, heat shock dermatitis, uveitis, vaginitis, vasculitis, and vulvitis.See also Eric R. First, Application of Botulinum Toxin to the Management of Neurogenic Inflammatory Disorders, U.S. Patent 6,063,768, which is hereby incorporated by reference in its entirety.

[0169] In one embodiment, chronic inflammation includes tissue inflammation. Tissue inflammation is chronic inflammation that is localized 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, pancreatic inflammation, kidney inflammation, bladder inflammation, stomach inflammation, intestinal inflammation, neuronal inflammation, and brain inflammation.

[0170] In another embodiment, chronic inflammation includes systemic inflammation. Although the processes involved are the same as those for tissue inflammation, systemic inflammation is not confined to specific tissues but rather encompasses the entire body, involving the endothelium and other organ systems. When systemic inflammation is due to infection, the term sepsis is used, with the term bacteremia being used specifically for bacterial sepsis and viremia being used specifically for viral sepsis. Vasodilation and organ dysfunction are serious problems associated with widespread infection that can lead to septic shock and death.

[0171] In another embodiment, chronic inflammation comprises arthritis. Arthritis comprises a group of conditions involving damage to the body's joints caused by inflammation of the synovium, 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, crystal synovitis, 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 an autoimmune disease or a non-autoimmune disease.

[0172] In another embodiment, chronic inflammatory disease comprises autoimmune disorder.Depending on the main clinicopathological features of every kind of disease, autoimmune disease can be roughly divided into systemic autoimmune disorder and organ specific autoimmune disorder.Systemic autoimmune disease includes but is not limited to systemic lupus erythematosus (SLE), Sjögren's syndrome (Sjogren's syndrome), scleroderma, rheumatoid arthritis and polymyositis.Local autoimmune disease can be endocrinological (type 1 diabetes, Hashimoto's thyroiditis, Addison's disease (Addison's disease) etc.), dermatological (pemphigoid vulgaris), hematological (autoimmune hemolytic anemia), neurological (multiple sclerosis) or can relate to the clear-cut lump of almost any body tissue. Types of autoimmune disorders include, but are not limited to, acute disseminated encephalomyelitis (ADEM), Addison's disease, allergies or sensitivities, amyotrophic lateral sclerosis, antiphospholipid antibody 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, inflammatory bowel disease,

[0013] Examples of the present invention include, but are not limited to, idiopathic cystitis, lupus (including discoid lupus erythematosus, drug-induced lupus erythematosus, 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 Publication No. 2006 / 138059, which is hereby incorporated by reference in its entirety.

[0173] In another embodiment, chronic inflammation includes myopathy. Myopathy is caused when the immune system inappropriately attacks components of muscle, leading to muscle inflammation. Myopathy includes inflammatory myopathy and autoimmune myopathy. Myopathy includes, but is not limited to, dermatomyositis, inclusion body myositis, and polymyositis.

[0174] In another embodiment, chronic inflammation includes vasculitis. Vasculitis is a diverse group of disorders characterized by inflammation of the blood vessel walls, including lymphatic vessels and blood vessels such as veins (phlebitis), arteries (arteritis), and capillaries, due to the migration of white blood cells and the resulting damage. Inflammation may affect blood vessels of any size anywhere in the body. It may affect arteries and / or veins. Inflammation may be focal, meaning it affects a single location within a blood vessel; or it may be widespread, with areas of inflammation scattered throughout a specific organ or tissue, or even affecting more than one organ system in the body. Vasculitis includes, but is not limited to, Buerger's disease (thromboangiitis obliterans), cerebral vasculitis (vasculitis of the central nervous system), Churg-Strauss arteritis, cryoglobulinemia, essential cryoglobulinemic vasculitis, giant cell (temporal) arteritis, Golfer's vasculitis, Henoch-Schonlein 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 connective tissue disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), relapsing polychondritis, Behcet's disease or other connective tissue disorders, and vasculitis secondary to viral infections.

[0175] In another embodiment, chronic inflammation comprises a skin disorder. Skin disorders include, but are not limited to, acne (including acne vulgaris), bullous pemphigoid, dermatitis (including atopic dermatitis and chronic actinic dermatitis), eczema such as atopic eczema, contact eczema, dry eczema, seborrheic dermatitis, dyshidrosis, discoid eczema, venous eczema, dermatitis herpetiformis, neurodermatitis and autoeczematous and stasis dermatitis, hidradenitis suppurativa, lichen planus, psoriasis (including plaque psoriasis, nail psoriasis, guttate psoriasis, scalp psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis), rosacea and scleroderma (including morphea).

[0176] In another embodiment, the chronic inflammatory disease comprises a gastrointestinal disorder. Gastrointestinal disorders include, but are 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.

[0177] In another embodiment, chronic inflammation includes cardiovascular disease. When LDL cholesterol becomes embedded in the arterial wall, it can trigger an immune response. Chronic inflammation can eventually damage the arteries, which can cause arterial rupture. Cardiovascular disease is any of many specific diseases that affect the heart itself and / or the vascular system, particularly the veins and arteries leading to and from 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 disease; vascular inflammation, such as arteritis, phlebitis, vasculitis; arterial occlusive disease, such as arteriosclerosis and stenosis, inflammatory cardiac hypertrophy, peripheral arterial disease; aneurysm; embolism; dissection (dissection); pseudoaneurysm; vascular malformation; vascular nevus; thrombosis; thrombophlebitis; varicose veins; stroke. Symptoms of cardiovascular disorders affecting the heart include but are not limited to chest pain or chest discomfort (angina), pain in one or both arms, left shoulder, neck, jaw or back, shortness of breath, dizziness, rapid heartbeat, nausea, abnormal heartbeat, and feeling tired. 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 visual disturbances in one or both eyes, sudden dizziness, difficulty walking or loss of balance or coordination, sudden severe headaches of unknown cause. Symptoms of cardiovascular disorders affecting the legs, pelvis, and / or arms include, but are not limited to, claudication (which is pain, persistent ache, or cramp in the muscles), and cold or numb feelings in the feet or toes, especially at night.

[0178] In another embodiment, chronic inflammation includes cancer. Inflammation coordinates the microenvironment around the tumor, contributing to proliferation, survival, and migration. For example, fibrinous inflammation is caused by a large increase in vascular permeability that allows fibrin to pass through the blood vessels. If there is an appropriate procoagulant stimulus such as cancer cells, fibrinous exudate is deposited. This is usually seen in the serosal cavity, where the conversion of fibrinous exudate to scarring can occur between the serosal membranes, limiting their function. In another example, the cancer is an inflammatory cancer such as an NF-κB-driven inflammatory cancer.

[0179] In another embodiment, chronic inflammation includes pharmacologically induced inflammation. Certain drugs or exogenous compounds are known to affect inflammation. For example, vitamin A deficiency causes an increase in inflammatory response.

[0180] In another embodiment, chronic inflammation includes infection. Infectious organisms can escape the limitation of direct tissue via the circulatory system or lymphatic system, and in the circulatory system or lymphatic system, infectious organisms can spread to other parts of the body. If the organism is not controlled by the effect of acute inflammation, it may enter the lymphatic system via nearby lymphatic vessels. The infection of the lymphatic vessels is called lymphangitis, and the infection of the lymph nodes is called lymphadenitis. Pathogens can enter the circulatory system and enter the bloodstream through lymphatic drainage. Infection includes but is not limited to bacterial cystitis, bacterial encephalitis, pandemic influenza, viral encephalitis and viral hepatitis (type A, type B and type C).

[0181] In another embodiment, chronic inflammation comprises tissue or organ damage.Tissue or organ damage includes, but is not limited to, burns, lacerations, wounds, punctures, or trauma.

[0182] In another embodiment, chronic inflammation includes transplant rejection. When the transplanted organ or tissue is not accepted by the transplant recipient's body due to the recipient's immune system attacking the transplanted organ or tissue, transplant rejection occurs. The adaptive immune response, i.e., transplant rejection, is mediated by both T cell-mediated immune (antibody) mechanisms and humoral immunity (antibody) mechanisms. Transplant rejection can be classified as hyperacute rejection, acute rejection, or chronic rejection. Chronic rejection of transplanted organs or tissues is a chronic inflammatory and immune response in which rejection is due to little known information about 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 the functional immune cells in the transplanted bone marrow recognize the recipient as "foreign" and launch an immune attack. In some cases, it can also occur in blood transfusions. GVHD is divided into acute and chronic forms. Acute GVHD and chronic GVHD appear to involve different immune cell subsets, different cytokine profiles, slightly different host targets, and different responses to treatment.

[0183] In another embodiment, chronic inflammation includes Th1-mediated inflammatory diseases. In a well-functioning immune system, the immune response should result in a well-balanced pro-inflammatory Th1 response and an anti-inflammatory Th2 response suitable for resolving the immune attack. In general, once the pro-inflammatory Th1 response is initiated, the body relies on the anti-inflammatory response triggered by the Th2 response to antagonize the Th1 response. This antagonistic response includes the release of Th2-type cytokines, such as IL-4, IL-5, and IL-13, which are related to the promotion of IgE and eosinophil responses in atopy; and IL-10, which has an anti-inflammatory response. Th1-mediated inflammatory diseases involve excessive pro-inflammatory responses that result in chronic inflammation produced by Th1 cells. Th1-mediated diseases can be viral, bacterial, or chemical (e.g., environmental) induced. For example, viruses that cause Th1-mediated diseases can cause chronic infections or acute infections, which can cause respiratory disorders or influenza.

[0184] In another embodiment, chronic inflammation includes chronic neurogenic inflammation.Chronic neurogenic inflammation refers to the inflammatory response caused and / or maintained by releasing inflammatory molecules such as SP or CGRP, which are released from peripheral sensory nerve endings (i.e., a kind of efferent function, contrary to the normal afferent signal conduction to the spinal cord in these nerves).Chronic neurogenic inflammation includes both primary inflammation and secondary neurogenic inflammation.As used herein, term "primary" neurogenic inflammation refers to the tissue inflammation (inflammatory symptoms) caused by the release of substances from primary sensory nerve endings (such as C fibers and A-δ fibers) or the release of substances.As used herein, term "secondary" neurogenic inflammation refers to the tissue inflammation caused by the non-neuronal sources (for example, from vascular beds or from extravasation of tissue interstitial matter, such as from mast cells or immune cells) of inflammatory mediators such as peptides or cytokines, stimulates sensory nerve endings and causes inflammatory mediators to be released from nerves. The net effect of both forms of chronic neurogenic inflammation (primary and secondary) is an inflammatory state that is maintained by sensitization of peripheral sensory nerve fibers. The physiological consequences of the resulting chronic neurogenic inflammation depend on the tissue in question, producing symptoms such as, for example, skin pain (allodynia, hyperalgesia), joint pain and / or arthritis, visceral pain and dysfunction, lung dysfunction (asthma, COPD), and bladder dysfunction (pain, overactive bladder).

[0185] Neuroinflammation includes both acute neuroinflammation and chronic neuroinflammation. Acute neuroinflammation usually follows central nervous system damage and is characterized by rapid activation of microglia, release of inflammatory molecules, endothelial cell activation, platelet deposition, and tissue edema. Chronic neuroinflammation is the persistent activation of glial cells and the recruitment of other immune cells into the brain. However, over time, chronic inflammation causes degradation of tissues and the BBB, and reactive oxygen species produced by microglia and inflammatory signals released by microglia recruit peripheral immune cells to help establish a neuroimmune response.

[0186] Chronic inflammation is often associated with neurodegenerative diseases. Neurodegenerative diseases are caused by the progressive loss of neuronal structure or function, a process known as neurodegeneration. This neuronal damage may ultimately lead to cell death. Neurodegeneration can be found at many different levels of neuronal circuitry in the brain, 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 contributors to neurodegeneration are oxidative stress and neuroinflammation. Non-limiting examples of neurodegenerative diseases associated with neuroinflammation include Alzheimer's disease, amyotrophic lateral sclerosis, aneurysm, anxiety disorders, 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 disorders, postoperative cognitive decline, post-traumatic stress disorder, SARS-CoV-2 infection, schizophrenia, stroke, substance abuse-derived neuroinflammation, traumatic brain injury, and Tourette syndrome.

[0187] The composition or compound is administered to an individual. The individual is typically a human. Generally, any individual who is a candidate for conventional chronic inflammation and / or neuroinflammation treatment is a candidate for chronic inflammation and / or neuroinflammation treatment disclosed herein. In addition to comprehensive informed consent for all relevant risks and benefits of the disclosed procedure, preoperative evaluation typically includes a routine medical history and physical examination (including biomarker evaluation).

[0188] The pharmaceutical compositions disclosed herein may comprise 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 reference to treating chronic inflammation and / or neuroinflammation, refers to the minimum dose of a fibrate disclosed herein necessary to achieve the desired therapeutic effect, and includes a dose sufficient to reduce the symptoms associated with chronic inflammation and / or neuroinflammation. The effectiveness of the fibrates disclosed herein in treating chronic inflammation and / or neuroinflammation can be determined by observing individual improvements based on one or more clinical symptoms and / or physiological indicators associated with the condition. Improvement in chronic inflammation and / or neuroinflammation can also be indicated by a reduced need for concurrent therapy.

[0189] The appropriate effective amount of the fibrates disclosed herein for a particular chronic inflammation and / or neuroinflammation administered to an individual can be determined by one of ordinary skill 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 (including release, absorption, distribution, metabolism and excretion) of the specific fibrate used, the pharmacodynamic properties (including mechanism of action, dose-response relationship) of the specific fibrate used, the desired activity, undesirable side effects, the therapeutic window and duration of action, the nature of the other compounds included in the composition, the specific formulation, the specific route of administration, the specific characteristics, medical history and risk factors of the patient such as, for example, age, weight, general health, etc., or any combination thereof. It is known to one of ordinary skill in the art that the effective amount of the fibrates disclosed herein can be inferred from in vitro assays using animal models and in vivo administration studies prior to administration to humans. In addition, given the varying efficiencies of various routes of administration, it is expected that the necessary effective amount will vary. For example, the oral administration of fibrates disclosed herein will generally be expected to require a higher dosage level than intravenous administration. Similarly, the systemic administration of fibrates disclosed herein will be expected to require a higher dosage level than topical administration. The variation of these dosage levels can be regulated using the empirical optimization program of standard, which is well known to those of ordinary skill in the art. Those skilled in the art will also recognize that individual conditions can be monitored during the whole method disclosed herein or purposes, and the effective amount of fibrates disclosed herein used can be adjusted accordingly. Therefore, accurate treatment effective dose level and pattern are preferably determined by the attending healthcare professional in the case of considering the factors determined above.

[0190] In some embodiments, a therapeutically effective amount of a fibrate disclosed herein reduces symptoms associated with chronic inflammation and / or neuroinflammation by, e.g., 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, e.g., at most 10%, at most 15%, at most 20%, at most 25%, at most 30%, at most 35%, at most 40%, at most 45%, at most 50%, at most 55%, at most 60%, at most 65%, at most 70%, at most 75%, at most 80%, at most 85%, at most 90%, at most 95%, or at most 100%. In yet other aspects of this embodiment, a therapeutically effective amount of a fibrate disclosed herein reduces symptoms associated with chronic inflammation and / or neuroinflammation by, e.g., 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 70%, 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%.

[0191] In some embodiments, the therapeutically effective amount of a fibrate disclosed herein is generally in the range of about 0.01 mg / kg to about 10 mg / kg. In aspects of these embodiments, the effective amount of a fibrate disclosed herein can 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 can be, for example, at most 0.01 mg / kg, at most 0.05 mg / kg, at most 0.1 mg / kg, at most 0.5 mg / kg, at most 1.0 mg / kg, at most 2.0 mg / kg, at most 3.0 mg / kg, at most 4.0 mg / kg, at most 5.0 mg / kg, at most 6.0 mg / kg, at most 7.0 mg / kg, at most 8.0 mg / kg, at most 9.0 mg / kg, or at most 10 mg / kg.In yet other aspects of these embodiments, an effective amount of a fibrate disclosed herein can be in the range of, 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 , about 0.01 mg / kg to about 7.0 mg / kg, about 0.01 mg / kg to about 8.0 mg / kg, about 0.01 mg / kg to about 9.0 mg / kg, about 0.01 mg / kg to about 10 mg / kg, about 0.1 mg / kg to about 0.5 mg / kg, about 0.1 mg / kg to about 1.0 mg / kg, about 0.1 mg / kg to about 2.0 mg / kg, about 0.1 mg / kg to about 3.0 mg / kg, about 0.1 mg / kg to about 4.0 mg / kg, about 0.1 mg / kg to about 5.0 mg / kg, about 0.1 mg / kg to about 6.0 mg / kg, about 0. 1 mg / kg to about 7.0 mg / kg, about 0.1 mg / kg to about 8.0 mg / kg, about 0.1 mg / kg to about 9.0 mg / kg, about 0.1 mg / kg to about 10 mg / kg, about 0.5 mg / kg to about 1.0 mg / kg, about 0.5 mg / kg to about 2.0 mg / kg, about 0.5 mg / kg to about 3.0 mg / kg, about 0.5 mg / kg to about 4.0 mg / kg, about 0.5 mg / kg to about 5.0 mg / kg, about 0.5 mg / kg to about 6.0 mg / kg, about 0.5 mg / kg to about 7.0 mg / kg, about 0.5 mg / kg to about In some embodiments, the present invention provides a method for treating a patient with a certain degree of hemoglobin infection in an amount of about 10 mg / kg to about 8.0 mg / 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.

[0192] In some embodiments, the therapeutically effective amount of a fibrate disclosed herein is generally in the range of about 0.01 mg / kg / day to about 10 mg / kg / day. In aspects of these embodiments, the effective amount of a fibrate disclosed herein can 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 can be, for example, at most 0.01 mg / kg / day, at most 0.05 mg / kg / day, at most 0.1 mg / kg / day, at most 0.5 mg / kg / day, at most 1.0 mg / kg / day, at most 2.0 mg / kg / day, at most 3.0 mg / kg / day, at most 4.0 mg / kg / day, at most 5.0 mg / kg / day, at most 6.0 mg / kg / day, at most 7.0 mg / kg / day, at most 8.0 mg / kg / day, at most 9.0 mg / kg / day, or at most 10 mg / kg / day. In yet other aspects of these embodiments, an effective amount of a fibrate disclosed herein can be in the range of, for example, about 0.01 mg / kg / day to about 0.05 mg / kg / day, about 0.01 mg / kg / day to about 0.1 mg / kg / day, about 0.01 mg / kg / day to about 0.5 mg / kg / day, about 0.01 mg / kg / day to about 1.0 mg / kg / day, about 0.01 mg / kg / day to about 2.0 mg / kg / day, about 0.01 mg / kg / day to about 3.0 mg / kg / day, about 0.01 mg / kg / day to about 4.0 mg / kg / day, about 0.01 mg / kg / day to about 5.0 mg / kg / day, about 0.01 mg / kg / day to about 6.0 mg / kg / day. 0 mg / kg / day, about 0.01 mg / kg / day to about 7.0 mg / kg / day, about 0.01 mg / kg / day to about 8.0 mg / kg / day, about 0.01 mg / kg / day to about 9.0 mg / kg / day, about 0.01 mg / kg / day to about 10 mg / kg / day, about 0.1 mg / kg / day to about 0.5 mg / kg / day, about 0.1 mg / kg / day to about 1.0 mg / 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, 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 1.0 mg / kg / day to about 7.0 mg / kg / day, about 1.0 mg / kg / day to about 8.0 mg / kg / day, about 1.0 mg / kg / day to about 9.0 mg / kg / day, or about 1.0 mg / kg / day to about 10 mg / kg / day.

[0193] Administration can be a single dose or cumulative (continuous administration), and can be easily determined by those skilled in the art. For example, the treatment of chronic inflammation and / or neuroinflammation can include a one-time administration of an effective dose of a pharmaceutical composition disclosed herein. Alternatively, the treatment of chronic inflammation and / or neuroinflammation can include multiple administrations of an effective dose of a pharmaceutical composition carried out over a series of time periods, such as, for example, once a day, twice a day, three times a day, once every few days, or once a week. The time of administration can vary between individuals, depending on factors such as the severity of individual symptoms. For example, an effective dose of a pharmaceutical composition disclosed herein can be administered once a day to an individual for an indefinite period of time, or until the individual no longer needs treatment. Those of ordinary skill in the art will recognize that the condition of the individual can be monitored throughout the treatment process, and the effective amount of the pharmaceutical composition disclosed herein administered can be adjusted accordingly.

[0194] In one embodiment, a pharmaceutical composition comprising a fibrate disclosed herein, upon administration to a subject, results in a biodistribution of the fibrate that is different from the biodistribution of the fibrate contained in the same pharmaceutical composition but without the one or more digestion enhancing agents disclosed herein.

[0195] In some embodiments, the pharmaceutical composition comprises one or more fibrates, one or more glycerolipids, and one or more digestion enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, the one or more digestion enhancers 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof, and the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0196] 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 glycerides, and about 0.1% to about 40% by weight of one or more digestion 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 glycerides, and about 0.1% to about 40% by weight of one or more digestion enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, the one or more digestion 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof, and the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0197] 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 glycerides, and about 0.1% to about 10% by weight of one or more digestion 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 glycerides, and about 0.1% to about 10% by weight of one or more digestion enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, the one or more digestion enhancers 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof, and the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0198] 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 digestion 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 digestion enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, the one or more digestion enhancers 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof, and the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0199] 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 digestion 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 digestion enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, the one or more digestion 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof, and the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0200] In some embodiments, the pharmaceutical composition comprises fenofibrate, one or more glycerolipids, and one or more digestion enhancers. In some embodiments, the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0201] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate, from about 50% to about 95% by weight of one or more glycerolipids, and from about 0.1% to about 40% by weight of one or more digestion enhancers. In some embodiments, the pharmaceutical composition comprises from about 25 mg / mL to about 300 mg / mL of fenofibrate, from about 50% to about 95% by weight of one or more glycerolipids, and from about 0.1% to about 40% by weight of one or more digestion enhancers. In some embodiments, the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0202] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate, from about 50% to about 95% by weight of one or more glycerolipids, and from about 0.1% to about 10% by weight of one or more digestion enhancers. In some embodiments, the pharmaceutical composition comprises from about 25 mg / mL to about 300 mg / mL of fenofibrate, from about 50% to about 95% by weight of one or more glycerolipids, and from about 0.1% to about 10% by weight of one or more digestion enhancers. In some embodiments, the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0203] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate, from about 50% to about 95% by weight of one or more glycerolipids, and from about 5% to about 40% by weight of one or more digestion enhancers. In some embodiments, the pharmaceutical composition comprises from about 25 mg / mL to about 300 mg / mL of fenofibrate, from about 50% to about 95% by weight of one or more glycerolipids, and from about 5% to about 40% by weight of one or more digestion enhancers. In some embodiments, the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0204] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate, from about 50% to about 85% by weight of one or more glycerolipids, and from about 10% to about 40% by weight of one or more digestion enhancers. In some embodiments, the pharmaceutical composition comprises from about 25 mg / mL to about 300 mg / mL of fenofibrate, from about 50% to about 85% by weight of one or more glycerolipids, and from about 10% to about 40% by weight of one or more digestion enhancers. In some embodiments, the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0205] 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 digestion enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, the one or more digestion enhancers 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof, and the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C14-24 Fatty acid surfactant or any combination thereof.

[0206] 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 digestion 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, 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 digestion enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, the one or more digestion enhancing agents 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof, and the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0207] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of one or more fibrates; from about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising glycerolipids; from about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of monoglycerides, diglycerides, and triglycerides; and from about 0.1% to about 40% by weight of one or more digestion 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, the one or more hard fats comprising glycerides; about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerides, the partially hydrolyzed glycerides comprising a mixture of monoglycerides, diglycerides, and triglycerides; and about 0.1% to about 40% by weight of one or more digestion enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, the one or more digestion enhancers 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof, and the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant 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 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C24 Diacylglycerol and C 10 -C 24 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 one or more fibrates; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 mixture of triglycerides; and about 0.1% to about 40% by weight of one or more digestion enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, the one or more digestion enhancers 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof, and the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0209] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of one or more fibrates; from about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 one or more fibrates; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 mixture of triglycerides; and about 0.1% to about 40% by weight of one or more digestion enhancers. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, the one or more digestion enhancers 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof, and the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0210] In some embodiments, the pharmaceutical composition comprises fenofibrate, one or more hard fats, one or more liquid fats, and one or more digestion enhancers. In some embodiments, the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0211] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% by weight of fenofibrate, 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 digestion enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, 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 digestion enhancers. In some embodiments, the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0212] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% by weight of fenofibrate; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising glycerolipids; about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of monoglycerides, diglycerides, and triglycerides; and about 0.1% to about 40% by weight of one or more digestion enhancers. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising glycerides; about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerides, the partially hydrolyzed glycerides comprising a mixture of monoglycerides, diglycerides, and triglycerides; and about 0.1% to about 40% by weight of one or more digestion enhancers. In some embodiments, the one or more digestion enhancers comprise one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0213] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate; from about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 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; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 and about 0.1% to about 40% by weight of one or more digestion enhancing agents. In some embodiments, the one or more digestion enhancing agents include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0214] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate; from about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 and about 0.1% to about 40% by weight of one or more digestion enhancing agents. In some embodiments, the one or more digestion enhancing agents include one or more bile acids, one or more free C 14-24 Fatty acids, one or more free C 14-24 Fatty acid surfactant or any combination thereof.

[0215] In some embodiments, the pharmaceutical composition includes one or more fibrates, one or more hard fats, one or more liquid fats and one or more bile acids. In some embodiments, one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthofen, ronifibrate, simfibrate or any combination thereof. In some embodiments, one or more bile acids in the above embodiments include cholic acid. In some embodiments, one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthofen, ronifibrate, simfibrate or any combination thereof, and one or more bile acids in the above embodiments include cholic acid.

[0216] In some embodiments, the pharmaceutical composition includes one or more fibrates of about 0.1% to about 25% by weight, one or more hard fats of about 40% to about 50% by weight, one or more liquid fats of about 30% to about 50% by weight, and one or more bile acids of about 0.1% to about 10% by weight. In some embodiments, the pharmaceutical composition includes one or more fibrates of about 25mg / mL to about 300mg / mL, one or more hard fats of about 40% to about 50% by weight, one or more liquid fats of about 30% to about 50% by weight, and one or more bile acids of about 0.1% to about 10% by weight. In some embodiments, one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, 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, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments comprise cholic acid.

[0217] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of one or more fibrates; from about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising glycerolipids; from about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of monoglycerides, diglycerides, and triglycerides; and from 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, the one or more hard fats comprising glycerides; about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerides, the partially hydrolyzed glycerides comprising a mixture of monoglycerides, diglycerides 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 comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate 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, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, simfibrate, or any combination thereof, and the one or more bile acids in the above embodiments comprise cholic acid.

[0218] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of one or more fibrates; from about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24mixture 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; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 A mixture of triglycerides; and one or more bile acids of about 0.1% to about 10% by weight. In some embodiments, one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments include cholic acid. In some embodiments, one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate, or any combination thereof, and one or more bile acids in the above embodiments include cholic acid.

[0219] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of one or more fibrates; from about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18mixture 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; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 A mixture of triglycerides; and one or more bile acids of about 0.1% to about 10% by weight. In some embodiments, one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments include cholic acid. In some embodiments, one or more fibrates in the above embodiments include bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate, or any combination thereof, and one or more bile acids in the above embodiments include cholic acid.

[0220] 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.

[0221] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% fenofibrate by weight, about 40% to about 50% of one or more hard fats by weight, about 30% to about 50% of one or more liquid fats by weight, and about 0.1% to about 10% of one or more bile acids by weight. In some embodiments, the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate, about 40% to about 50% of one or more hard fats by weight, about 30% to about 50% of one or more liquid fats by weight, and about 0.1% to about 10% of one or more bile acids by weight. In some embodiments, the one or more bile acids in the above embodiments comprise bile acid.

[0222] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% by weight of fenofibrate; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising glycerolipids; about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of monoglycerides, diglycerides, 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 fenofibrate; about 40% to about 50% by weight of one or more hard fats, wherein the one or more hard fats comprise glycerides; about 30% to about 50% by weight of one or more liquid fats, wherein the one or more liquid fats comprise partially hydrolyzed glycerides, wherein the partially hydrolyzed glycerides include a mixture of monoglycerides, diglycerides, 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 comprise bile acid.

[0223] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate; from about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24mixture 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; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 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 comprise cholic acid.

[0224] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate; from about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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; about 40% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C16 -C 18 Diacylglycerol and C 16 -C 18 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 comprise cholic acid.

[0225] 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 Fatty acids. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate or any combination thereof, and one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate or any combination thereof, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, the one or more bile acids in the above embodiments comprise cholic acid, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof.

[0226] 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 Fatty acids. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate or any combination thereof, and one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate or any combination thereof, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, the one or more bile acids in the above embodiments comprise cholic acid, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof.

[0227] 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, the one or more hard fats comprising glycerides; from about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerides, the partially hydrolyzed glycerides comprising a mixture of monoglycerides, diglycerides, 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 Fatty acids. 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, the one or more hard fats comprising glycerides; about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerides, the partially hydrolyzed glycerides comprising a mixture of monoglycerides, diglycerides, 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 Fatty acids. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate or any combination thereof, and one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate or any combination thereof, and one or more free C 14-24 Fatty acids contain one or more free C 14-18Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, the one or more bile acids in the above embodiments comprise cholic acid, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof.

[0228] 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, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 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; about 25% to about 50% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 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 14-24Fatty acids. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate or any combination thereof, and one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate or any combination thereof, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, the one or more bile acids in the above embodiments comprise cholic acid, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof.

[0229] 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, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C18 Diacylglycerol and C 16 -C 18 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; about 25% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acids. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naproxen, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate or any combination thereof, and one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, simfibrate or any combination thereof, and one or more free C 14-24 Fatty acids contain one or more free C 14-18Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, the one or more bile acids in the above embodiments comprise cholic acid, and the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof.

[0230] 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 14-24 In some embodiments, one or more bile acids in the above embodiments comprise bile acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof.

[0231] In some embodiments, the pharmaceutical composition comprises about 0.1% to about 25% by weight 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 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, one or more bile acids in the above embodiments comprise bile acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof.

[0232] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate; from about 25% to about 50% by weight of one or more hard fats, the one or more hard fats comprising glycerides; from about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerides, the partially hydrolyzed glycerides comprising a mixture of monoglycerides, diglycerides, 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 Fatty acids. 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, the one or more hard fats comprising glycerides; about 30% to about 50% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerides, the partially hydrolyzed glycerides comprising a mixture of monoglycerides, diglycerides, 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, one or more bile acids in the above embodiments comprise bile acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof.

[0233] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate; from about 25% to about 50% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 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 Fatty acids. 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, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 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, one or more bile acids in the above embodiments comprise bile acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof.

[0234] In some embodiments, the pharmaceutical composition comprises from about 0.1% to about 25% by weight of fenofibrate; from about 25% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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; about 25% to about 50% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 50% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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, one or more bile acids in the above embodiments comprise bile acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof.

[0235] 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 14-24Fatty acid surfactants. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, and one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate 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 surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise bile acid, and one or more free C 14-24 Fatty acids contain one or more free C 14-18Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactant, preferably oleic acid alkali metal or alkaline earth metal salt, stearic acid alkali metal or alkaline earth metal salt, linoleic acid alkali metal or alkaline earth metal salt or any combination thereof. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic 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 surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, one or more bile acids in the above embodiments comprise bile acid, and one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, the one or more bile acids in the above embodiments comprise cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, one or more free C in the above embodiments 14-24 Fatty acids contain one or more free C 14-18Fatty acids, preferably oleic acid, stearic 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 surfactant, preferably oleic acid alkali metal or alkaline earth metal salt, stearic acid alkali metal or alkaline earth metal salt, linoleic acid alkali metal or alkaline earth metal salt or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments comprise bile acid, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic 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 surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, one or more bile acids in the above embodiments comprise bile acid, one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic 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 surfactant, preferably alkali metal or alkaline earth metal salt of oleic acid, alkali metal or alkaline earth metal salt of stearic acid, alkali metal or alkaline earth metal salt of linoleic acid, or any combination thereof.

[0236] 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 from about 0.1% to about 5% by weight of one or more free C 14-24Fatty acid surfactants. 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 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 from about 0.1% to about 5% by weight of one or more free C 14-24 Fatty acid surfactants. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, and one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18Fatty acid surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise bile acid, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactant, preferably oleic acid alkali metal or alkaline earth metal salt, stearic acid alkali metal or alkaline earth metal salt, linoleic acid alkali metal or alkaline earth metal salt or any combination thereof. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic 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 surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, one or more bile acids in the above embodiments comprise bile acid, and one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, the one or more bile acids in the above embodiments comprise cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18Fatty acid surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, one or more free C in the above embodiments 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic 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 surfactant, preferably oleic acid alkali metal or alkaline earth metal salt, stearic acid alkali metal or alkaline earth metal salt, linoleic acid alkali metal or alkaline earth metal salt or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments comprise bile acid, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic 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 surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, one or more bile acids in the above embodiments comprise bile acid, one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic 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 surfactant, preferably alkali metal or alkaline earth metal salt of oleic acid, alkali metal or alkaline earth metal salt of stearic acid, alkali metal or alkaline earth metal salt of linoleic acid, or any combination thereof.

[0237] 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 40% by weight of one or more hard fats, the one or more hard fats comprising glycerides; from about 30% to about 45% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerides, the partially hydrolyzed glycerides comprising a mixture of monoglycerides, diglycerides, and triglycerides; from about 0.1% to about 10% by weight of one or more bile acids; and from about 10% to about 25% by weight of one or more free C 14-24 Fatty acids; and from about 0.1% to about 5% by weight of one or more free C 14-24 Fatty acid surfactant. 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 40% by weight of one or more hard fats, the one or more hard fats comprising glycerides; about 30% to about 45% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed glycerides, the partially hydrolyzed glycerides comprising a mixture of monoglycerides, diglycerides, 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 from about 0.1% to about 5% by weight of one or more free C 14-24 Fatty acid surfactants. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18Fatty acid surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, and one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate 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 surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate, or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise bile acid, and one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, one or more bile acids in the above embodiments comprise cholic acid, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactant, preferably oleic acid alkali metal or alkaline earth metal salt, stearic acid alkali metal or alkaline earth metal salt, linoleic acid alkali metal or alkaline earth metal salt or any combination thereof. In some embodiments, one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18Fatty acid surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, one or more bile acids in the above embodiments comprise bile acid, and one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof. In some embodiments, the one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, the one or more bile acids in the above embodiments comprise cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, one or more free C in the above embodiments 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic 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 surfactant, preferably oleic acid alkali metal or alkaline earth metal salt, stearic acid alkali metal or alkaline earth metal salt, linoleic acid alkali metal or alkaline earth metal salt or any combination thereof. In some embodiments, the one or more bile acids in the above embodiments comprise bile acid, the one or more free C 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic acid, linoleic acid or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18Fatty acid surfactant, preferably alkali metal or alkaline earth metal salt of oleate, alkali metal or alkaline earth metal salt of stearate, alkali metal or alkaline earth metal salt of linoleate or any combination thereof. In some embodiments, one or more fibrates in the above embodiments comprise bezafibrate, ciprofibrate, clinofibrate, clofibrate, clobemide, etofibrate, fenofibrate, fenofibric acid, gemfibrozil, naphthopine, ronifibrate, bisfibrate or any combination thereof, one or more bile acids in the above embodiments comprise bile acid, one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 Fatty acids, preferably oleic acid, stearic 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 surfactant, preferably alkali metal or alkaline earth metal salt of oleic acid, alkali metal or alkaline earth metal salt of stearic acid, alkali metal or alkaline earth metal salt of linoleic acid, or any combination thereof.

[0238] 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 40% by weight of one or more hard fats, the one or more hard fats comprising C 10 -C 24 Triglycerides; about 30% to about 45% by weight of one or more liquid fats, said one or more liquid fats comprising partially hydrolyzed triglycerides comprising C 10 -C 24 Monoglyceride, C 10 -C 24 Diacylglycerol and C 10 -C 24 A mixture of triglycerides; about 0.1% to about 10% by weight of one or more b...

Claims

1. A pharmaceutical composition comprising one or more fibrates, one or more glycerides, one or more bile acids, one or more free C 14 -C 24 Fatty acids, one or more free C 14 -C 24 A fatty acid surfactant or any combination thereof for use in treating inflammation.

2. The pharmaceutical composition for use according to claim 1, wherein the inflammation is neuroinflammation.

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

4. A pharmaceutical composition for use according to any one of claims 1 to 3, wherein the one or more glycerolipids are provided in an amount between 50% and 95% by weight of the composition.

5. The pharmaceutical composition for use according to any one of claims 1 to 4, wherein the one or more glycerolipids comprise one or more hard fats and one or more liquid fats.

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

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

8. A pharmaceutical composition for use according to claim 5 or 6, wherein the one or more hard fats comprise one or more triglycerides.

9. The pharmaceutical composition for use according to claim 8, wherein the one or more triglycerides comprise or consist of: Saturated and / or unsaturated C 10 -C 18 A mixture of triglycerides and / or saturated and / or unsaturated C 12 -C 18 A mixture of triglycerides.

10. The pharmaceutical composition for use according to claim 5 or 7, wherein the one or more liquid fats comprise a mixture of monoglycerides, diglycerides and triglycerides.

11. The pharmaceutical composition for use according to claim 10, wherein the mixture of monoglycerides, diglycerides and triglycerides comprises C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 A mixture of triglycerides.

12. A pharmaceutical composition for use according to any one of claims 1-11, wherein the one or more hard fats are provided at between 25% and 40% by weight of the composition.

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

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

1.

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

16. A pharmaceutical composition for use according to any one of claims 1 to 15, wherein the one or more bile acids comprise or consist of: Cholic acid, chenodeoxycholic acid, cholic acid, deoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, lithocholic acid, taurochenodeoxycholic acid, taurocholic acid, any stereoisomers thereof, and any combination thereof.

17. A pharmaceutical composition for use according to any one of claims 1-16, wherein the one or more bile acids are provided in an amount between 0.1% and 10% by weight of the composition.

18. A pharmaceutical composition for use according to any one of claims 1 to 17, wherein the one or more free C 14 -C 24 Fatty acids include palmitic acid (hexadecanoic acid), palmitolenic acid, palmitoid acid, palmitic vaccenic acid, palmitoleic acid, cis-6-hexadecenoic acid, 4-hexadecenoic acid, stearic acid (octadecenoic acid), α-linolenic acid, octadecatetraenoic acid, α-eleostearic acid, β-eleostearic acid, punicic acid, 7,10,13-octadecatrienoic acid, 12-octadecenoic acid, linoleic acid, trans-linoleic acid, gamma-linolenic acid, calendula acid, pinolenic acid, vaccinic acid, rumenic acid, oleic acid, trans-oleic acid, petroselinic acid, arachidic acid (eicosanoic acid), dihomo-α-linolenic acid, eicosatetraenoic acid, eicosapentaenoic acid, 9,12,15-eicosatrienoic acid oleic acid, cis-4,7,10,13,16-docosapentaenoic acid, erucic acid, lignoceric acid, 9,12,15,18,21-eicosapentaenoic acid, 6,9,12,15,18,21-eicosapentaenoic acid, and neuraminic acid.

19. The pharmaceutical composition for use according to claim 18, wherein the one or more free C 14 -C 24 The fatty acids include oleic acid, stearic acid, linoleic acid, or any combination thereof.

20. A pharmaceutical composition for use according to any one of claims 1 to 19, wherein the one or more free C 14 -C 24 Fatty acids are provided in an amount of between 10% and 25% by weight of the composition.

21. A pharmaceutical composition for use according to any one of claims 1 to 20, wherein the one or more free C 14 -C 24 The fatty acid surfactant is selected from the list consisting of sodium palmitate (sodium hexadecanoate), sodium palm linolenate, sodium palm idonic acid, sodium palm vaccinate, sodium palm oleate, sodium cis-6-hexadecenoate, sodium 4-hexadecenoate, sodium stearate (sodium octadecenoate), sodium α-linolenate, sodium octadecatenate, sodium α-eleostearate, sodium β-eleostearate, sodium punicate, sodium 7,10,13-octadecatrienoate, sodium 12-octadecenoate, sodium linoleate, sodium trans-linoleate, sodium gamma-linolenate, sodium calendulanate, sodium pinolenate, sodium vaccinate, sodium rumenate, sodium oleate, sodium trans-oleate, sodium petroselinate, sodium arachidate (sodium eicosanoate), sodium dihomo-α-linolenate, sodium eicosate, sodium eicosapentaenoate, 9 , sodium 1,2,15-eicosatrienoate, sodium β-eicosatetraenoate, sodium dihomo-linoleate, sodium dihomo-γ-linolenate, sodium arachidonic acid, sodium eicosenoate, sodium 7,10,13-eicosatrienoate, sodium chelidonic acid, sodium 8,11-eicosadienoate, sodium mead acid, sodium cis-9-eicosenoate, sodium 8-eicosenoate, sodium behenate (sodium docosanoate), sodium oleate, sodium docosahexaenoate, sodium adrenaline, sodium cis-4,7,10,13,16-docosapentaenoate, sodium erucate, sodium lignocerate (sodium tetracosanoate), sodium 9,12,15,18,21-tetracospentaenoate, sodium 6,9,12,15,18,21-tetracosahexenoate and sodium neuraminic acid.

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

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

24. A pharmaceutical composition for use according to any one of claims 5 to 23, comprising 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 Fatty acid surfactant.

25. A pharmaceutical composition for use in treating neuroinflammation, 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 Fatty acid surfactant.

26. The pharmaceutical composition for use according to claim 25, comprising about 10% to about 20% by weight of fenofibrate; about 26% to about 36% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 26% to about 36% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 A mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; 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 Fatty acid surfactant.

27. The pharmaceutical composition for use according to claim 25 or 26, comprising about 12% to about 18% by weight of fenofibrate; about 28% to about 34% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 28% to about 34% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

28. A pharmaceutical composition for use according to any one of claims 25-27, comprising about 14% to about 16% by weight of fenofibrate; about 30% to about 32% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 32% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

29. The pharmaceutical composition for use according to claim 25, comprising about 25 mg / mL to about 300 mg / mL of fenofibrate; about 28% to about 34% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 28% to about 34% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

30. The pharmaceutical composition for use according to claim 25 or 29, comprising about 35 mg / mL to about 200 mg / mL of fenofibrate; about 28% to about 34% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 28% to about 34% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

31. The pharmaceutical composition for use according to claim 25, 29 or 30, comprising about 70 mg / mL to about 150 mg / mL of fenofibrate; about 30% to about 32% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 32% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

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

33. A pharmaceutical composition for use according to any one of claims 25 to 32, wherein the one or more free C 14-24 Fatty acids contain one or more free C 14-18 fatty acid.

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

35. A pharmaceutical composition for use according to any one of claims 25-34, wherein the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactant.

36. The pharmaceutical composition for use according to claim 35, wherein the one or more free C 14-18 The fatty acid surfactant comprises an alkali metal or alkaline earth metal salt of oleic acid, an alkali metal or alkaline earth metal salt of stearic acid, an alkali metal or alkaline earth metal salt of linoleic acid, or any combination thereof.

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

38. A method of treating an individual suffering from neuroinflammation, the method comprising the step of administering to an individual in need thereof a 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 Fatty acid surfactant.

39. The method of claim 38, wherein the pharmaceutical composition comprises about 10% to about 20% by weight of fenofibrate; about 26% to about 36% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 26% to about 36% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 A mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; 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 A fatty acid surfactant, wherein administration results in a reduction in symptoms associated with said inflammation, thereby treating said individual.

40. The method of claim 38 or 39, wherein the pharmaceutical composition comprises about 12% to about 18% by weight of fenofibrate; about 28% to about 34% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 28% to about 34% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

41. The method of any one of claims 38-40, wherein the pharmaceutical composition comprises about 14% to about 16% by weight of fenofibrate; about 30% to about 32% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 32% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

42. The method of claim 38, wherein the pharmaceutical composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate; about 28% to about 34% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 28% to about 34% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

43. The method of claim 38 or 42, wherein the pharmaceutical composition comprises about 35 mg / mL to about 200 mg / mL of fenofibrate; about 28% to about 34% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 28% to about 34% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

44. The method of claim 38, 42 or 43, wherein the pharmaceutical composition comprises about 70 mg / mL to about 150 mg / mL of fenofibrate; about 30% to about 32% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 32% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

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

46. ​​The method of any one of claims 38-45, wherein the one or more free C 14-24 Fatty acids contain one or more free C 14-18 fatty acid.

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

48. The method of any one of claims 38-47, wherein the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactant.

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

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

51. Use of a pharmaceutical composition in the manufacture of a medicament for treating neuroinflammation, 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 Fatty acid surfactant.

52. The use according to claim 51, wherein the composition comprises from about 10% to about 20% by weight of fenofibrate; from about 26% to about 36% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 26% to about 36% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 A mixture of triglycerides; about 3% to about 7% by weight of one or more bile acids; 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 Fatty acid surfactant.

53. The use according to claim 51 or 52, wherein the composition comprises from about 12% to about 18% by weight of fenofibrate; from about 28% to about 34% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 28% to about 34% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

54. The use according to any one of claims 51-53, wherein the composition comprises from about 14% to about 16% by weight of fenofibrate; from about 30% to about 32% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 32% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

55. The use according to claim 51, wherein the composition comprises about 25 mg / mL to about 300 mg / mL of fenofibrate; about 28% to about 34% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 28% to about 34% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

56. The use according to claim 51 or 55, wherein the composition comprises about 35 mg / mL to about 200 mg / mL of fenofibrate; about 28% to about 34% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 28% to about 34% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

57. The use according to claim 51, 55 or 56, wherein the composition comprises about 70 mg / mL to about 150 mg / mL of fenofibrate; about 30% to about 32% by weight of one or more hard fats, the one or more hard fats comprising saturated C 10 -C 18 Triglycerides and / or saturated C 12 -C 18 A mixture of triglycerides; about 30% to about 32% by weight of one or more liquid fats, the one or more liquid fats comprising partially hydrolyzed triglycerides, the partially hydrolyzed triglycerides comprising C 16 -C 18 Monoglyceride, C 16 -C 18 Diacylglycerol and C 16 -C 18 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 Fatty acid surfactant.

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

59. The use according to any one of claims 51-58, wherein the one or more free C 14-24 Fatty acids contain one or more free C 14-18 fatty acid.

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

61. The use according to any one of claims 51-60, wherein the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 Fatty acid surfactant.

62. The use according to claim 61, wherein the one or more free C 14-18 The fatty acid surfactant comprises an alkali metal or alkaline earth metal salt of oleic acid, an alkali metal or alkaline earth metal salt of stearic acid, an alkali metal or alkaline earth metal salt of linoleic acid, or any combination thereof.

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

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