Compositions with improved bioavailability of therapeutic agents and uses thereof - Patents.com

Abstract

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

Description

[Technical field]

[0001] This international patent application claims the benefit of priority and is entitled to the filing dates of International Patent Application No. PCT / EP2022 / 058180, filed March 28, 2022, U.S. Patent Application No. 17 / 656,702, filed March 28, 2022, and U.S. Provisional Patent Application No. 63 / 269,330, filed March 14, 2022, the contents of each of which are incorporated herein by reference in their entirety. [Background technology]

[0002] Oral delivery of therapeutic compounds is the most preferred route of administration, accounting for 80% of all pharmaceutical compositions on the market. The premise underlying traditional oral delivery is that the therapeutic compound must first be released from the composition into the gastrointestinal fluids, absorbed by the capillaries lining the duodenum of the small intestine, and then distributed throughout the body by the bloodstream. However, the effectiveness of oral delivery typically depends on the pharmacokinetic properties of the pharmaceutical composition and the therapeutic compound formulated therein, with the amount of therapeutic compound released from the pharmaceutical composition (dissolution rate) and the amount of therapeutic compound absorbed into the systemic circulation and made available to the body (or bioavailability) being two major critical factors.

[0003] Both poorly water-soluble or hydrophobic therapeutic compounds present particularly difficult oral delivery challenges due to their low aqueous solubility and slow dissolution rate in the aqueous gastrointestinal environment. To solve these problems, the pharmaceutical industry has traditionally focused on optimizing the formulation of pharmaceutical compositions in a manner that 1) improves the dissolution rate of the hydrophobic therapeutic compound in the formulation, thereby increasing the amount released to the gastrointestinal tract, and / or 2) improves the bioavailability of the hydrophobic therapeutic compound, thereby increasing the amount delivered systemically to the body.

[0004] For hydrophilic therapeutic compounds, the formulation challenges are different. Although these compounds are readily soluble in the aqueous gastrointestinal environment, many are poorly absorbed due to poor membrane permeability and / or enzymatic degradation. Many solid dosage formulations of hydrophilic therapeutic compounds exhibit poor or no absorption of the therapeutic compound.

[0005] One approach to improve the pharmacokinetics of pharmaceutical compositions containing hydrophobic therapeutic compounds has been to ingest the pharmaceutical composition with a high-fat containing meal to promote absorption in the small intestine and thus increase its bioavailability. Ingestion of a meal triggers the digestive process in the stomach, including the release of bile from the gallbladder into the duodenum, where it breaks down and absorbs fat from the food. Such a meal generally does not affect the dissolution rate, but the absorption of the released therapeutic compound enters the systemic circulation in greater amounts due to the simultaneous absorption of fat from the meal.

[0006] Another approach to improve the pharmacokinetics of pharmaceutical compositions containing hydrophobic therapeutic compounds has been the use of phospholipid-based formulations, including macroemulsions, microemulsions, self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), self-nanoemulsifying drug delivery systems (SNEDDS), solid lipid nanoparticles (SLN), liposomes and lipoplexes. These surfactant-based formulations generate oil-based emulsions containing the therapeutic compounds that facilitate absorption by the small intestine into the systemic circulation, thus increasing the bioavailability of the therapeutic compounds. However, in addition to generally not affecting the dissolution rate, such surfactant-based formulations also destabilize the membrane lining the stomach, causing irritation. Further limitations associated with this approach include, for example, in vivo drug precipitation, formulation handling issues, limited lymphatic uptake, lack of predictive in vitro testing, and oxidation of unsaturated fatty acids, which limit their potential use. Thus, the wide variability of the bioavailability of therapeutic compounds remains a challenging obstacle.

[0007] The present specification provides an alternative approach whereby the pharmaceutical compositions disclosed herein are formulated to rely on the physiological lipid digestion and absorption system to achieve absorption and enhanced efficacy, increasing the bioavailability of therapeutic compounds to better facilitate the treatment of diseases or disorders. Moreover, such formulations are not only applicable to highly lipophilic therapeutic compounds, but also provide a means to increase the solubility of therapeutic compounds that are generally poorly soluble in both aqueous and lipid matrices. Summary of the Invention

[0008] Aspects of the present specification partially disclose pharmaceutical compositions comprising a) one or more therapeutic compounds, b) one or more glycerolipids, and c) one or more digestive enhancers. The therapeutic compounds disclosed herein can be hydrophilic therapeutic compounds, hydrophobic therapeutic compounds, or pharmaceutical active agents or components, diagnostic agents or components, cosmetic active agents or components, or nutraceutical active agents or components. The glycerolipids disclosed herein include hard fats and liquid fats. Hard fats are glycerolipids that are solid at 18°C ​​and contain triglycerides. Liquid fats are glycerolipids that are liquid at 18°C ​​and also include partially hydrolyzed glycerolipids and monoglycerides. The digestive enhancers disclosed herein include one or more bile acids, one or more phospholipids, one or more free C 14-24 The compositions disclosed herein may further comprise one or more pharma- ceutically acceptable stabilizing agents, including fatty acid surfactants, one or more fatty acid salts, one or more fatty acid derivatives with polyhydroxylated head groups, one or more steroid surfactants, or any combination thereof.

[0009] Another aspect herein discloses a method of treating an individual having a disease or disorder, comprising administering to the individual in need thereof a pharmaceutical composition disclosed herein, whereby administration alleviates symptoms associated with the disease or disorder, thereby treating the individual.

[0010] Other aspects of the present specification partially disclose pharmaceutical compositions for use in treating a disease or disorder, comprising a) one or more therapeutic compounds, b) one or more glycerolipids, and c) one or more digestive enhancers. The therapeutic compounds disclosed herein can be hydrophilic therapeutic compounds, hydrophobic therapeutic compounds, or pharmaceutical active agents or components, diagnostic agents or components, cosmetic active agents or components, or dietary supplement active agents or components. The glycerolipids disclosed herein include hard fats and liquid fats. Hard fats are glycerolipids that are solid at 18°C ​​and contain triglycerides. Liquid fats are glycerolipids that are liquid at 18°C ​​and also include partially hydrolyzed glycerolipids and monoglycerides. The digestive enhancers disclosed herein include one or more bile acids, one or more phospholipids, one or more free C 14-24 The compositions disclosed herein may further comprise one or more pharma- ceutically acceptable stabilizing agents, including fatty acid surfactants, one or more fatty acid salts, one or more fatty acid derivatives with polyhydroxylated head groups, one or more steroid surfactants, or any combination thereof.

[0011] Another aspect of the present specification discloses the use of a pharmaceutical composition disclosed herein in the manufacture of a medicament for treating a disease or disorder.

[0012] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate aspects of the disclosed subject matter in at least one of its exemplary embodiments, as defined in more detail in the following description. Features, elements, and aspects of the disclosure are referred to by numerals, with like numerals in different drawings representing the same, equivalent, or similar features, elements, or aspects according to one or more embodiments. The drawings are not necessarily to scale, emphasis instead being placed on illustrating principles described herein and provided by exemplary embodiments of the invention. In such drawings, [Brief description of the drawings]

[0013] [Figure 1A]1A shows a representative PXRD spectrum analyzing the disclosed pharmaceutical compositions containing fenofibrate. FIG. 1B shows a representative PXRD spectrum of GELCURE® 43 / 01 standard. [Figure 1B] 1A-1B show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate.FIG. 1B shows representative PXRD spectra of cholic acid standards. [Figure 1C] 1A-1C show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate and a representative PXRD spectrum of a fenofibrate standard. [Figure 1D] 1A-1D show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate and a vehicle standard. [Figure 1E] 1A-1E show representative PXRD spectra analyzing the disclosed pharmaceutical compositions containing fenofibrate and a fenofibrate standard. [Figure 1F] 1F shows a representative PXRD spectrum analyzing the disclosed pharmaceutical compositions containing fenofibrate. The figure shows a representative PXRD spectrum of a fenofibrate standard overlaid on a representative PXRD spectrum of a disclosed pharmaceutical composition containing a fenofibrate standard, with asterisks over the peaks indicating the overlap of the associated peaks. [Figure 1G] 1G shows a representative PXRD spectrum analyzing the disclosed pharmaceutical compositions containing fenofibrate. A representative PXRD spectrum of a cholic acid standard overlaid on a representative PXRD spectrum of a vehicle standard, with asterisks above the peaks indicating the overlap of the relevant peaks. [Figure 1H]1H shows a representative PXRD spectrum analyzing the disclosed pharmaceutical compositions containing fenofibrate.FIG. 1H shows a representative PXRD spectrum of a cholic acid standard overlaid on the disclosed pharmaceutical compositions containing fenofibrate standard, with asterisks above the peaks indicating overlap of the relevant peaks.

[0014] [Figure 2A] 2A shows a representative UHPLC tracing of fenofibric acid levels in blood after oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing fenofibrate. [Figure 2B] 2B shows a representative UHPLC tracing of fenofibric acid levels in the brain after oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing fenofibrate.

[0015] [Diagram 3] FIG. 3 shows a representative UHPLC tracing of mebendazole levels in blood following oral administration of 30 mg / kg of the disclosed pharmaceutical composition containing mebendazole.

[0016] [Figure 4] FIG. 4 shows a representative UHPLC tracing of olaparib levels in blood following oral administration of 30 mg / kg of the disclosed pharmaceutical composition comprising olaparib. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] The present disclosure discloses pharmaceutical compositions formulated for oral delivery in such a manner that the therapeutic compounds present in the pharmaceutical composition are preferentially taken up into the lymphatic system. The pharmaceutical compositions disclosed herein include one or more therapeutic compounds, one or more glycerolipids, and one or more digestive enhancers. The glycerolipids disclosed herein act as stabilizers that promote the dissolution of the therapeutic compounds disclosed herein into solution and / or prevent the therapeutic compounds disclosed herein from precipitating from the pharmaceutical composition. The digestive enhancers disclosed herein, in conjunction with the glycerolipids, increase the solubility of one or more therapeutic compounds in the glycerolipid matrix, increase the absorption of these compounds into the lymphatic system, and increase the availability of these compounds to their therapeutic targets. As shown herein, the disclosed pharmaceutical compositions formulated using one or more glycerolipids and one or more digestive enhancers disclosed herein minimize the increase in the bioavailability of the therapeutic compounds by maintaining higher levels of the therapeutic compounds for extended periods of time and increasing the directed biodistribution of the therapeutic compounds to their therapeutic targets. Moreover, in many cases, the disclosed pharmaceutical compositions allow the therapeutic compound to reach its maximum concentration in the shortest period of time, in addition to achieving the maximum amount of therapeutic compound exposure to its therapeutic target over time. Overall, the disclosed pharmaceutical compositions exhibit superior pharmacokinetic and pharmacodynamic profiles than current formulations of the same therapeutic compound, making the disclosed pharmaceutical compositions more effective and efficacious for their intended uses.

[0018] The majority of digestion of dietary organic macromolecules and almost all absorption of the resulting breakdown products occurs in the small intestine. The luminal wall of the small intestine is lined with many projections called villi, each of which contains enterocytes called absorptive epithelial cells. Not only do absorptive epithelial cells secrete enzymes that digest proteins (polypeptides), carbohydrates (polysaccharides), and fats (lipids), but these cells also absorb amino acid, monosaccharide, and fatty acid breakdown products. Interestingly, however, absorptive epithelial cells process these breakdown products differently, with amino acids and monosaccharides taken up by capillaries and transported throughout the body by the blood system, and fatty acids taken up by blind-ended lymphatic vessels called lacteals and then transported throughout the body by the lymphatic system. The disclosed pharmaceutical compositions take advantage of this differential processing by formulating therapeutic compounds that are preferentially processed by absorptive epithelial cells in a manner that allows these compounds to be taken up and transported int the lymphatic system.

[0019] Dietary lipids typically consumed by mammals comprise 90% triglycerides and small amounts of cholesterol esters and phospholipids. Unlike proteins and carbohydrates, dietary lipids are hydrophobic molecules that cannot dissolve in the fluids present in the lumen of the small intestine, but instead aggregate together to form fat globules. Pancreatic lipase is a water-soluble enzyme that cleaves ester bonds and breaks down lipid triglycerides into fatty acids and glycerol. However, due to its hydrophilicity, lipase remains in the intestinal fluids and is unable to dissolve in the fat globules, and can therefore only access and cleave triglycerides located at the surface where the fat globules and intestinal fluids come into contact. To increase the efficiency and rate of cleavage with which lipase can break down lipids in the small intestine, the liver produces a fluid called bile. Bile contains amphipathic molecules, such as bile salts including sodium cholate and sodium chenodeoxycholate, phospholipids including lecithin, and the hydrophobic steroid cholesterol. When bile is discharged into the small intestine, it mixes with the fat globules in a manner that bile salts and phospholipids intercalate with these structures, breaking them down into smaller units called emulsion droplets, and also recruits amphiphilic molecules called coliapses. 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 over which lipase can act on triglycerides, increasing its efficiency and catalytic rate, thereby allowing a sufficient amount of lipid digestion to take place in the small intestine.

[0020] As lipid triglyceride digestion progresses, the resulting free fatty acids, which are both hydrophobic and insoluble in intestinal fluids, associate with bile-derived phospholipids to form droplets called mixed micelles, whose composition is phospholipids and bile salts that encapsulate the free fatty acids. The mixed micelles, which are approximately 200-500 times smaller in size than emulsion droplets, fuse with the membranes of absorptive epithelial cells, where the free fatty acids enter the cytosol of these cells. Once inside the absorptive epithelial cells, the free fatty acids are transported to the lumen of the smooth endoplasmic reticulum, where they are converted back to triglycerides and assemble with cholesterol and phospholipids into globular lipid structures. These lipid structures are transported to the rough endoplasmic reticulum, where the apoprotein ApoB-48 binds to the surface to form large lipoproteins called chylomicrons. The chylomicrons are then packaged in the Golgi apparatus and exit via exocytosis to the basolateral side of the absorptive epithelial cells. Because chylomicrons are too large to be taken up by capillaries, these lipoproteins enter the lymphatic system via lacteals in a process that depends on ApoB-48. Chylomicrons then circulate through lymphatic vessels and are discharged into the blood system via the thoracic duct, bypassing the hepatic circulation. Once chylomicrons enter the blood system, these lipoproteins migrate to various extrahepatic tissues, where their triglycerides are hydrolyzed by the activity of lipoprotein lipase, allowing the released free fatty acids and glycerol to be absorbed by the tissues. When most of the triglycerides have been hydrolyzed, chylomicron remnants are formed and taken up by the liver, thereby also transporting dietary fat to this organ.

[0021] The present specification discloses a pharmaceutical composition that is formulated for oral delivery in such a manner that the fibrates present in the pharmaceutical composition are preferentially taken up into lymphatic system.The pharmaceutical composition disclosed herein comprises one or more fibrates, one or more glycerolipids, and one or more digestive enhancers.The digestive enhancers disclosed herein, in combination with glycerolipids, increase the solubility of one or more fibrates in glycerolipid matrix, increase the absorption of these compounds into lymphatic system, and increase the availability of these compounds to their therapeutic target.

[0022] The natural digestive process relies on the secretion of bile into ingested intestinal contents and their mixing with the intestinal contents to initiate access to other digestive processes such as emulsification and the activity of lipases. These processes must be completed for the drug to be absorbed. A complete gallbladder response associated with the ingestion of lipids secretes up to 50-60 mL of bile into the duodenum. The present invention relies on the intimate mixing of a digestive enhancer with a fibrate in the preparation of a pharmaceutical composition disclosed herein that can then be orally ingested by the patient. The fibrate is then presented to the intestinal lumen in a form that is ready for immediate ingestion. This process is highly efficient because the digestive enhancer is intimately mixed with the formulation lipid excipients. Without wishing to be limited by any theory, the pharmaceutical compositions disclosed herein use ingredients that are products of triglyceride digestion to mimic the conditions brought about by a high-fat meal. The formulation allows one or more fibrates contained therein to be enveloped in micelles along with free fatty acids and absorbed by the absorptive epithelial cells, which then package the one or more fibrates into chylomicrons. Then, fibrate-loaded chylomicrons are transported by lymphatic system to their target cells, where fibrates are taken up by these cells to exert their beneficial effects.In essence, chylomicrons are employed as a drug delivery system for one or more fibrates contained in the pharmaceutical composition disclosed herein.By controlling the composition and amount of one or more glycerolipids and one or more digestive enhancers, the pharmaceutical composition disclosed herein provides a more consistent and predictable bioavailability of one or more fibrates disclosed herein, which can be further achieved by relying on a high-fat meal.

[0023] The pharmaceutical compositions disclosed herein are advantageous for several reasons, all of which ultimately increase the bioavailability and efficacy of one or more fibrates contained therein. For example, the pharmaceutical compositions disclosed herein deliver their fibrates via the lymphatic system. The use of the lymphatic system to deliver fibrates is beneficial for several reasons. First, the lymphatic system avoids pre-systemic metabolism, which reduces the bioavailability of many fibrates administered using traditional oral delivery approaches. Also referred to as the first-pass effect or first-pass metabolism, fibrates absorbed by the digestive system must first enter the hepatic portal system before reaching the systemic circulation. Meanwhile, in the hepatic portal system, fibrates can be metabolized by hepatic enzymes in the liver, which reduces the amount of fibrates that enter the systemic circulation. Thus, delivery of fibrates via the lymphatic system acts as a bypass to the hepatic portal system for fibrates that are susceptible to hepatic metabolism. The lymphatic uptake system represents an attractive opportunity for preferential delivery of drugs. However, small water-soluble molecules that follow the laws of paracellular absorption (e.g., Lipinski's law) are not ideal substrates for lymphatic uptake. Additional highly lipophilic molecules often have poor and variable bioavailability even when absorbed by lymphatic uptake. The present invention uses a broad family of digestive enhancers in lipid delivery systems to enable both small molecule Lipinski-compatible drugs and highly lipophilic drugs to be effectively delivered through the lymphatic uptake route.

[0024] In addition, the lymphatic administration route can help to directly deliver fibrates to their target cells, thereby increasing their bioavailability and decreasing their clearance rate.For example, fibrate-loaded chylomicrons transported to the lymphatic system are discharged into the thoracic artery and circulate throughout the body via the arterial system to reach the capillary bed, where they are extracavated into the surrounding tissues and taken up by target cells.Fibrate-loaded chylomicrons that are not taken up by target cells and are removed from the extracellular environment by interstitial fluid are then taken up by lacteals, transported by the lymphatic system, and discharged into the thoracic artery, where they are recirculated again systemically throughout the body.Such lymphatic-based administration results in more fibrates being delivered to various systems, organs and tissues due to the avoidance of the hepatic portal system mentioned above. Furthermore, as more of the fibrate enters the general circulation, its elimination, ie, metabolism and excretion, is prolonged, thereby slowing the clearance rate of the compound and effectively increasing its half-life.

[0025] Another advantage of the disclosed pharmaceutical composition is the use of chylomicrons to selectively biodistribute one or more fibrates contained therein to immune cells, such as macrophages and dendritic cells. For example, there are several processes by which macrophages can take up chylomicrons. First, macrophages circulating in lymph and blood secrete lipoprotein lipase, and chylomicrons are the substrate for this enzymatic activity, resulting in the uptake of chylomicron proteins and lipids, and thus any fibrates contained within the chylomicron. Furthermore, the exogenous lipoprotein metabolic pathway, through a series of processing events, converts chylomicrons into LDL particles, which are oxidized by ROS to generate oxidized LDL particles. The FAT / CD36 scavenger receptors located on the membrane of macrophages bind and endocytose these oxidized LDL particles, including any fibrates contained therein. Finally, these fibrate-loaded macrophages are directed to cells undergoing pathological damage where the fibrates can be delivered to these damaged cells.

[0026] Furthermore, when processed into micelles in the small intestine, the components of the disclosed pharmaceutical compositions are believed to mimic pathogen-associated molecular patterns (PAMPs). Absorption of these micelles by the gut-associated lymphoid tissue (GALT) of the small intestine leads to subsequent uptake by immune cells such as macrophages and dendritic cells through a pattern recognition receptor-mediated process. In addition, since these micelles share structural similarities with chylomicrons, it is believed that these micelles can also be taken up via the process of macrophage lipoprotein lipase described above.

[0027] The disclosed pharmaceutical compositions are also advantageous because the ingredients used in their formulation mimic the signals that induce bile and pancreatic lipoprotein lipase secretion, enhancing the rate of micelle formation and increasing the rate of epithelial cell absorption of the micelles beyond that achieved with the use of digestive enhancers in the formulation alone. Such characteristics increase the rate and amount of fibrate that enters the lymphatic system and therefore its bioavailability.

[0028] In addition to preferential uptake into lymphatic system and selective biodistribution to immune cells, the disclosed pharmaceutical composition has several additional advantages.For example, fibrates are poorly water-soluble or hydrophobic therapeutic compounds, which have been found difficult to formulate in a therapeutically effective manner, for example, due to insolubility or instability in solution resulting in precipitation.Moreover, it has been surprisingly found that a significantly higher concentration of fibrates can be formulated into the pharmaceutical composition disclosed herein compared to currently known formulations.Moreover, the disclosed pharmaceutical composition comprising one or more fibrates dramatically increases the dissolution rate and bioavailability of these compounds.

[0029] Yet another advantage of the disclosed pharmaceutical compositions is the enhanced specificity of one or more fibrates for cellular targets. Chylomicrons contain membrane-bound proteins that function as ligands that associate with their cognate receptors located on the membrane surface of cells. One such ligand for these large lipoprotein particles is a protein that interacts with lipid transfer proteins. When fibrate-loaded chylomicrons are shed for absorption, cells that express high levels of lipid transfer proteins on their cell membranes preferentially bind and internalize these lipoprotein particles. For example, the brain has high levels of lipid transfer proteins on its cell membranes, allowing it to cross the blood-brain barrier, and other epithelial tissues such as the choroid plexus. This mechanism thereby increases the efficacy of these compounds. Other cells that express high levels of lipid transfer proteins on their cell membranes include immune cells, cardiac cells, adipocytes, liver cells and cancer cells. Cardiac cells express high levels of lipid transfer proteins on their surface, and therefore, we may expect increased cardiotoxicity for therapeutic compounds delivered via lymphatic routes. However, cardiotoxicity of therapeutic compounds is generally associated with high C maxThis is caused by high concentrations of free compounds, resulting in GPCR or ion channel-related pathology. Surprisingly, therefore, lipid delivery of therapeutic compounds may result in lower cardiac toxicity than expected, as these targets are protected from high concentrations of free compounds, as they are only slowly released from the chylomicron phase. Thus, the use of the pharmaceutical compositions disclosed herein may also be associated with reduced cardiac side effects and reduced toxicity. Furthermore, upon ingestion, the therapeutic compounds remain embedded in the oily / fatty excipient, limiting the opportunity for the compounds to solubilize in aqueous intestinal contents, thereby avoiding contact toxicity, such as gastric erosion and other local damage or harm. In addition to avoiding first-pass metabolism and local toxicity, enhanced uptake through the lymphatic pathway also minimizes the contact and availability of free therapeutic compounds further down the digestive tract. In this way, interactions and disruption of the gut microbiota can be minimized. This is particularly beneficial when using this technology with antibacterial agents. Furthermore, the anatomy of the lymphatic system allows the lungs to be effectively targeted with the appropriate agents. For example, anti-inflammatory, anti-fibrotic, antibacterial and bronchodilator drugs can be considered for ling targeting with lymphatic delivery using this technology.

[0030] Additionally, the disclosed pharmaceutical compositions are distinct from current surfactant-based formulations, such as, for example, macroemulsions, microemulsions, self-emulsifying drug delivery systems (SEDDS), self-microemulsifying drug delivery systems (SMEDDS), self-nanoemulsifying drug delivery systems (SNEDDS), solid lipid nanoparticles (SLN), liposomes, and lipoplexes. The disclosed pharmaceutical compositions are not emulsions or self-emulsifying compositions, and therefore avoid the side effects associated with these formulations, such as destabilizing the membrane lining the stomach and causing irritation. Additionally, the disclosed pharmaceutical compositions avoid manufacturing issues associated with current surfactant-based formulations, such as formulation handling issues and no predictive in vitro testing. The disclosed pharmaceutical compositions also avoid issues associated with current surfactant-based formulations, including, for example, in vivo drug precipitation, limited lymphatic uptake, and lack and oxidation of unsaturated fatty acids. Surprisingly, by mimicking the microenvironment of mixed micelles, the disclosed pharmaceutical compositions completely bypass the dissolution phase of drug uptake, resulting in significantly higher bioavailability of one or more fibrates contained therein. Unlike the self-emulsifying systems described above, the formulations disclosed herein are designed to avoid the formation of stable emulsions and do not undergo spontaneous emulsification when added to water (exhibiting the ouzo effect). Rather, when added to water, these materials are apparently immiscible.

[0031] Pharmaceutical Compositions Aspects of the present specification partially disclose compositions. The compositions disclosed herein are generally administered as pharmaceutical acceptable compositions. As used herein, the term "pharmaceutical acceptable" refers to any molecular entity or composition useful for preparing pharmaceutical compositions that are generally safe, non-toxic, and not biologically or otherwise undesirable, including those that are acceptable for veterinary and human medical use. As used herein, the term "pharmaceutical acceptable composition" is synonymous with "pharmaceutical composition" and refers to a combination of one or more therapeutic compounds disclosed herein combined with one or more glycerolipids, one or more digestion enhancers, and other ingredients disclosed herein to form a product that is administered to an individual. The pharmaceutical compositions disclosed herein are useful for medical and veterinary applications. The pharmaceutical compositions may be administered to an individual alone or in combination with other supplementary active ingredients, agents, drugs, or hormones.

[0032] The present disclosure discloses pharmaceutical compositions useful for formulating a wide variety of therapeutic compounds. In some embodiments, the pharmaceutical compositions disclosed herein include a) one or more therapeutic compounds, b) one or more glycerolipids, and c) one or more digestive enhancers. In some embodiments, the pharmaceutical compositions disclosed herein include a) one or more therapeutic compounds, b) one or more glycerolipids, c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24 In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, 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 therapeutic compounds, 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 C14-24 In all of the above embodiments, the one or more therapeutic compounds disclosed herein may include one or more hydrophilic therapeutic compounds, one or more poorly water-soluble or hydrophobic therapeutic compounds, or any combination thereof.

[0033] In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more partially hydrolyzed glycerolipids including one or more triglycerides, mixtures of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, and c) one or more digestive enhancers. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more partially hydrolyzed glycerolipids including one or more triglycerides, mixtures of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, and c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24 In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more partially hydrolyzed glycerolipids including one or more triglycerides, mixtures of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and / or one or more bile salts, and d) one or more phospholipids. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more partially hydrolyzed glycerolipids including one or more triglycerides, mixtures of mono-, di-, and triglycerides, or a combination of one or more triglycerides and one or more partially hydrolyzed glycerolipids, c) one or more bile acids and / or one or more bile salts, d) one or more phospholipids, and e) one or more free C 14-24In all of the above embodiments, the one or more therapeutic compounds disclosed herein may include one or more hydrophilic therapeutic compounds, one or more poorly water-soluble or hydrophobic therapeutic compounds, or any combination thereof.

[0034] In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, and c) one or more digestive enhancers. In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, b) one or more triglycerides, one or more monoglycerides, or a combination of one or more triglycerides and one or more monoglycerides, c) one or more bile acids and / or one or more bile salts, one or more phospholipids, one or more free C 14-24 In some embodiments, the pharmaceutical compositions disclosed herein comprise a) one or more therapeutic compounds, 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 therapeutic compounds, 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 In all of the above embodiments, the one or more therapeutic compounds disclosed herein may include one or more hydrophilic therapeutic compounds, one or more poorly water-soluble or hydrophobic therapeutic compounds, or any combination thereof.

[0035] The pharmaceutical compositions disclosed herein are formulated as anhydrous solids, solid dispersions, or molecular dispersions. Thus, the formulations of the disclosed pharmaceutical compositions do not contain any water. Furthermore, as mentioned above, the disclosed pharmaceutical compositions are not emulsions or self-emulsifying compositions. Thus, the pharmaceutical compositions disclosed herein behave like fats and oils in an aqueous environment, and maintain their hydrophobilc lipid characteristics when the lipid digestion process needs to break down for absorption. Emulsion occurs only when exposed to pancreatic juice from the small intestine. One reason is that the one or more glycerolipids and one or more digestive enhancers used are not amphiphilic enough to initiate emulsification, and these components require the action of bile secreted by the gallbladder during the digestive process to contribute to the formation of micellar structures. Another reason is that the bile acids, fatty acid surfactants, phospholipids, and any other digestive enhancers are all individually and in combination below the critical micelle concentration required for emulsification to occur.

[0036] therapeutic compounds Aspects of the present specification partially disclose therapeutic compounds. Therapeutic compounds are compounds that provide pharmacological activity or other direct effects in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the human or animal body. Therapeutic compounds include both synthetic small molecule therapeutic compounds and synthetic peptides, biological therapeutic compounds produced in, extracted from, or semi-synthesized from biological sources, including vaccines, whole blood, blood components, allergen agents, somatic cells, gene therapy, tissues, recombinant therapeutic proteins, and living medicines used in cell therapy.

[0037] Non-limiting examples of therapeutic compounds include pharmaceutical active agents or components, diagnostic agents or components, cosmetic active agents or components, and nutraceutical active agents or components. The therapeutic compounds disclosed herein may be used in the form of pharma-ceutically acceptable salts, solvates, or solvates of salts, such as hydrochloride salts. In addition, the therapeutic compounds disclosed herein may be provided as racemates or as individual enantiomers, including R- or S-enantiomers. Thus, the therapeutic compounds disclosed herein may include only the R-enantiomer, only the S-enantiomer, or a combination of both the R-enantiomer and the S-enantiomer of the therapeutic compound. The therapeutic compounds disclosed herein may be hydrophilic therapeutic compounds or hydrophobic therapeutic compounds.

[0038] The pharmaceutical compositions disclosed herein may include one or more therapeutic compounds based on the Biopharmaceutics Classification System (BCS) Class I-IV drugs. The BCS is a scientific framework for classifying drug substances based on their minimum aqueous solubility in the pH range of 1-7.5, absorbed dose and human fraction or intestinal membrane permeability (see USDepartment of Health and Human Services Food and Drug Administration Center for Evaluation and Research (CDER), Waiver of in vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, Guidance for Industry (2017), which is incorporated herein by reference in its entirety). When combined with formulation dissolution, the BCS considers three major factors that govern the rate and extent of drug absorption from IR solid oral dosage forms: (1) dissolution, (2) solubility, and (3) intestinal permeability. This system classifies drugs into four classes according to their permeability and solubility. BCS class I drugs are therapeutic compounds that have high solubility and high permeability and are generally completely absorbed. BCS class II drugs are therapeutic compounds that have low solubility and high permeability and are completely absorbed if in solution. BCS class III drugs are therapeutic compounds that have high solubility and low permeability and are difficult to completely absorb even though the drug is in solution (high dissolution rate). BCS class IV drugs are therapeutic compounds that have low solubility and low permeability and are difficult to put into solution and are poorly absorbed when in solution.Subclassification shaves have also been proposed based on whether therapeutic compounds from BCS classes I or III are acids, bases, or neutral (see Tsume, et al., The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC, Eur. J. Pharm. Sci. 57:152-163 (2014), which is incorporated by reference in its entirety).

[0039] In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more BCS class I therapeutic compounds, BCS class II therapeutic compounds, BCS class III therapeutic compounds, BCS class IV therapeutic compounds, or any combination thereof. In aspects of these embodiments, the pharmaceutical compositions disclosed herein may comprise one or more BCS class I therapeutic compounds. In aspects of these embodiments, the pharmaceutical compositions disclosed herein may comprise one or more BCS class II therapeutic compounds. In aspects of these embodiments, the pharmaceutical compositions disclosed herein may comprise one or more BCS class III therapeutic compounds. In aspects of these embodiments, the pharmaceutical compositions disclosed herein may comprise one or more BCS class IV therapeutic compounds.

[0040] The pharmaceutical compositions disclosed herein may comprise one or more hydrophilic therapeutic compounds.The hydrophilic therapeutic compounds disclosed herein include amphiphilic therapeutic compounds, which are water-soluble compounds with significant or substantial water solubility.In some embodiments, the hydrophilic therapeutic compounds disclosed herein have an inherent water solubility (i.e., the water solubility of the non-ionized form) of, for example, at least 0.1% by weight, at least 0.5% by weight, at least 1% by weight, or more typically at least 10% by weight.

[0041] The pharmaceutical compositions disclosed herein may comprise one or more hydrophobic therapeutic compounds.The hydrophobic therapeutic compounds disclosed herein include lipophilic therapeutic compounds, which are poorly water-soluble compounds with little or no water solubility.In some embodiments, the poorly water-soluble or hydrophobic therapeutic compounds disclosed herein have an intrinsic water solubility (i.e., the water solubility of the non-ionized form) of, for example, at most 1% (by weight), at most 0.5% (by weight), at most 0.1% (by weight), and more typically at most 0.01% (by weight).

[0042] In some embodiments, the therapeutic compounds disclosed herein are therapeutic compounds that contain an organic acid functional group, such as, for example, a carboxylic acid functional group or a sulfonic acid functional group. Examples of the disclosed therapeutic compounds that contain an organic acid functional group include free acid forms of the therapeutic compounds (i.e., therapeutic compounds with free organic acids) and salt forms of the therapeutic compounds (i.e., therapeutic compounds with organic acid salts). Organic acid salt forms of the therapeutic compounds include any therapeutic compound that is combined with an alkali metal, such as, for example, lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr), or an alkaline earth metal, such as, for example, beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra).

[0043] In some embodiments, the therapeutic compounds disclosed herein are therapeutic compounds that contain an organic base functional group, such as an amine functional group. Examples of the disclosed therapeutic compounds that contain an organic base functional group include therapeutic compounds that contain an organic base functional group that can donate ions. In some embodiments, the therapeutic compounds that contain an organic base functional group that can donate ions are therapeutic compounds that contain an amine functional group that can donate ions, including, but not limited to, primary amines, secondary amines, tertiary amines, amides, amidines, amidos, aminos, imidates, imides, imines, iminos, iminohydroxyls, and quaternary salts.

[0044] Non-limiting examples of therapeutic compounds include analgesics (including opioids and non-opioids), anesthetics, antibacterials (including antibiotics), anticonvulsants, anti-dementia agents, antidepressants, antidotes and antitoxins, antiemetics, antifungals, anti-inflammatory agents (including corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and nonsteroidal anti-inflammatory drugs (NSAIDs)), antimigraine agents, antimyasthenic agents, antimycobacterial agents, antineoplastic agents, antiparasitic agents, antiparkinsonian agents, antipsychotic agents, antiviral agents (including HIV antiretrovirals and direct acting hepatitis C agents), anxiolytic (anti-anxiety) agents, bipolar agents, blood glucose regulators (including insulin and other diabetes medications), blood products (including anticoagulants), cardiovascular agents (including beta blockers, ACE inhibitors, and statins). and PPAR agonists), central nervous system agents (including amphetamines), dental and oral agents, dermatological (skin) agents, enzyme replacement agents, gastrointestinal agents (including H2 blockers and proton pump inhibitors), urogenital (reproductive and urinary tract) agents, hormonal agents (adrenal, pituitary, prostaglandins, sex hormones (including estrogen, testosterone, and anabolic steroids, and thyroid), hormonal suppressants (adrenal, parathyroid, pituitary, sex hormones, and thyroid), immunological agents, inflammatory bowel disease agents, metabolic bone disease agents, nootropics, ophthalmic agents, otic agents, respiratory tract agents (including antihistamines and bronchodilators), sedatives and hypnotics, skeletal muscle relaxants, and those classified in the United States Pharmacopeia (USP), including therapeutic nutrients, minerals, and electrolytes.

[0045] Non-limiting examples of therapeutic compounds include 5-alpha-reductase inhibitors, 5-aminosalicylates, 5HT3 receptor antagonists, adamantanes, corticosteroids, corticosteroid inhibitors, hypertensive emergencies, pulmonary hypertension agents, aldosterone receptor antagonists, alkylating agents, allergens, alpha-glucosidase inhibitors, alternative medicines, amebicide agents, aminoglycosides, aminopenicillins, aminosalicylates, amphetamines, AMPA receptor antagonists, amylin analogs, analgesics, androgens, anabolic steroids, angiogenics, androgens, anabolic steroids, androgens ... Otensin-converting enzyme (ACE) inhibitors, angiotensin II inhibitors, angiotensin receptor blockers, appetite suppressants, antacids, antiadrenergics, antiandrogens, antianginals, antiarrhythmics, antiasthmatics, anxiolytics, antibiotics, anticholinergics, anticoagulants, anticoagulant reversals, anticonvulsants, antidepressants, antidiabetic agents, antidiarrheals, antidotes, antiemetics, antifungals, antigonadotropins, antigout agents, anthelmintics, antihistamines, antihyperlipidemics, antihypertensives, antihyperuricemics, anti-infectives, antimalarials, antimaniacs, antimetabolites, antimigraine agents, antineoplastic agents, antineoplastic detoxifiers, antineoplastic agents Neoplastic interferons, antiparkinsonian agents, antiplatelet agents, antipseudomonal penicillins, antipsoriatic agents, antipsychotic agents, antirheumatic agents, antirosacea agents, antiseptics and bactericides, antispasmodics, antithyroid agents, antitoxins and antivenins, antituberculous agents, antitussives, antivertigo agents, antivirals, antiviral boosters, anxiolytics, sedatives, and hypnotics, aromatase inhibitors, astringents, atypical antipsychotics, azoles, barbiturates, BCR-ABL tyrosine kinase inhibitors, benzodiazepines, beta blockers, beta-adrenergic blockers, beta-lactamase inhibitors, bile acid sequestrants, bisphosphonates , bone morphogenetic proteins, bone resorption inhibitors, bronchodilator combinations, bronchodilators, BTK inhibitors, calcimimetics, calcineurin inhibitors, calcitonin, calcium channel blockers, carbapenems, carbonic anhydrase inhibitors, cardiac stress agents, cardioselective beta blockers, cardiovascular agents, catecholamines, CDK4 / 6 inhibitors, central nervous system agents, cephalosporins, earwax, CFTR enhancers, CGRP inhibitors, chelating agents, chemokine receptor antagonists, chloride channel activators, cholesterol absorption inhibitors, cholinergic agonists, cholinergic muscle stimulants,Cholinesterase inhibitors, Chronotropes, CNS stimulants, Coagulation regulators, Colony stimulating factors, Corticosteroids, Corticotropins, Coumarins and indanediones, COX-2 inhibitors, Decongestants, Diarylquinolines, Dibenzazepines, Diagnostic dyes, Dipeptidyl peptidase 4 inhibitors, Disease-modifying antirheumatic drugs (DMARDs), Diuretics, Echinocandins, EGFR inhibitors, Erythropoietic agents, Estrogen receptor antagonists, Estrogens, Expectorants, Factor Xa inhibitors, Fibric acid derivatives, First generation cephalosporins, Fourth generation cephalosporins , functional bowel disorder agents, gallstone dissolving agents, gamma-aminobutyric acid analogues, gamma-aminobutyric acid reuptake inhibitors.gastrointestinal agents, genitourinary tract agents, GI stimulants, glucocorticoids, glucose elevating agents, glycoprotein platelet inhibitors, glycylcyclines, gonadotropin releasing hormone, gonadotropin releasing hormone antagonists, gonadotropins, class I antiarrhythmics, class II antiarrhythmics, class III antiarrhythmics, class IV antiarrhythmics, class V antiarrhythmics, growth hormone receptor blockers, growth hormone, guanylate cyclase C agonists, H. pylori eradication agents, H2 antagonists, hepatitis C inhibitors, Edgehog pathway inhibitors, hematopoietic stem cell mobilizers, heparin antagonists, heparin, HER2 inhibitors, herbal products, histone deacetylase inhibitors, hormones, hydantoins, hydrazide derivatives, immunological agents, immunostimulants, immunosuppressants, impotence agents, incretin mimetics, inotropes, insulin, insulin-like growth factors, integrase strand transfer inhibitors, interferons, interleukin inhibitors, interleukins, intravenous nutrition products, investigational drugs, iodized contrast media, iron products, ketolides, anti-leprosy agents, leukotriene modifiers, lincomycin derivatives, local injectable anesthetics Anesthetics, lymphatic stains, macrolide derivatives, macrolides, magnetic resonance imaging contrast agents, malignant tumor photosensitizers, mast cell stabilizers, meglitinides, melanocortin receptor agonists, metabolic agents, methylxanthines, mineralocorticoids, minerals and electrolytes, mitotic inhibitors, monoamine oxidase inhibitors, mTOR inhibitors, mucolytic agents, multikinase inhibitors, muscle relaxants, mydriatics, neprilysin inhibitors, neuraminidase inhibitors, neuromuscular blocking agents, neural potassium channel openers, NHE3 inhibitors, nicotinic acid derivatives, NK1 receptor antagonists,Non-opioids, NNRTIs, non-cardioselective beta blockers, non-sulfonylureas, non-steroidal anti-inflammatory drugs, nootropics, NS5A inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), dietary supplements, nutritional products, ophthalmic agents, opioids, otic agents, oxazolidinediones, parathyroid hormone and analogs, PARP inhibitors, PCSK9 inhibitors, penicillins, peripheral opioid receptor antagonists, peripheral opioid receptor mixed agonists / antagonists, peripheral vasodilators, peripherally acting anti-obesity agents, phenothiazines, phenylpiperazines, phosphate binders, P I3K inhibitors, plasma expanders, platelet aggregation inhibitors, platelet stimulants, polyenes, probiotics, progesterone receptor modulators, progestins, prolactin inhibitors, prostaglandin D2 antagonists, protease inhibitors, protease-activated receptor-1 antagonists, proteasome inhibitors, proton pump inhibitors, PPAR agonists, psoralens, psychotherapeutic agents, purine nucleosides, pyrrolidines, quinolones, radiocontrast agents, radioadjuvants, radiopharmaceuticals, renal replacement solutions, renin inhibitors, respiratory agents , rifamycin derivatives, salicylates, sclerosing agents, second generation cephalosporins, selective estrogen receptor modulators, selective immunosuppressants, selective phosphodiesterase-4 inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, serotonergic neuroenteric modulators, sex hormones, SGLT-2 inhibitors, skeletal muscle relaxants, smoking cessation agents, somatostatin and somatostatin analogues, spermicides, statins, streptogramins, streptomyces derivatives, succinimides, sulfonamides, sulfos These include nylurea, sympathomimetic amines, synthetic ovulation stimulants, tetracyclines, therapeutic radiopharmaceuticals, thiazides, thiazolidinediones, thioxanthenes, third generation cephalosporins, thrombin inhibitors, thrombolytics, thyroid medications, TNFα inhibitors, tocolytics, transthyretin stabilizers, triazines, urea cycle disruptors, urinary pH regulators, uterotonics, vasodilators, vasopressin antagonists, vasoconstrictors, VEGF / VEGFR inhibitors, viscosupplements, vitamins, and those classified as VMAT2 inhibitors.

[0046] The therapeutic compounds disclosed herein may be protein kinase inhibitors. Protein kinase inhibitors are a type of enzyme inhibitor that block the action of one or more protein kinases. Protein kinases are ubiquitous intracellular and cell surface proteins that play important roles in cell signaling pathways involved in metabolism, injury response, adaptation, growth, and differentiation. They usually act by adding phosphate groups to proteins (phosphorylation), often on specific amino acids that make the protein or enzyme "active." The human genome has over 500 protein kinases, which can be classified as tyrosine, serine-threonine, or non-specific (both) based on their amino acid specificity.

[0047] Tyrosine kinase inhibitors can be divided into two major families: receptor tyrosine kinase (RTK) inhibitors and non-receptor or cytoplasmic tyrosine kinase (nRTK) inhibitors. Non-limiting examples of RTK inhibitors include RTK class I inhibitors (EGF receptor family) (ErbB family), RTK class II inhibitors (insulin receptor family), RTK class III inhibitors (PDGF receptor family), RTK class IV inhibitors (VEGF receptor family), RTK class V inhibitors (FGF receptor family), RTK class VI inhibitors (CCK receptor family), RTK class VII inhibitors (NGF receptor family), RTK class VIII inhibitors (HGF receptor family), RTK class IX inhibitors (Eph receptor family), RTK class X inhibitors ( AXL receptor family), RTK class XI inhibitors (TIE receptor family), RTK class XII inhibitors (RYK receptor family), RTK class XIII inhibitors (DDR receptor family), RTK class XIV inhibitors (RET receptor family), RTK class XV inhibitors (ROS receptor family), RTK class XVI inhibitors (LTK receptor family), RTK class XVII inhibitors (ROR receptor family), RTK class XVIII inhibitors (MuSK receptor family), RTK class XIX inhibitors (LMR receptor), and RTK class XX inhibitors (until determined). Non-limiting examples of nRTK inhibitors include ABL nRTK inhibitors, ACK nRTK inhibitors, CSK nRTK inhibitors, FAK nRTK inhibitors, FES nRTK inhibitors, FRK nRTK inhibitors, JAK nRTK inhibitors, SRC nRTK inhibitors, SYK nRTK inhibitors, and TEC nRTK inhibitors.

[0048] Serine-threonine kinase (STK) inhibitors can be divided into two major families, receptor protein serine / threonine kinase (RSTK) inhibitors and non-receptor or cytoplasmic serine / threonine kinase (nRSTK) inhibitors. Non-limiting examples of receptor protein serine / threonine kinase inhibitors include polo kinase (PLK) inhibitors, cyclin-dependent kinase (CDK) inhibitors, (RNA-polymerase)-subunit kinase (RPS6K) inhibitors, mitogen-activated protein kinase (MAPK) inhibitors, MAPK kinase (MAPKK) inhibitors, MAPK kinase kinase (MAPKKK or MAP3K) inhibitors, tau-protein kinase (TPK) inhibitors, non-specific serine / threonine protein kinase inhibitors, pyruvate dehydrogenase kinase (PDK) inhibitors, dephospho-(reductase kinase) kinase inhibitors, 3-methyl-2-oxobutanoate dehydrogenase (ACE) inhibitors, and 3-methyl-2-oxobutanoate dehydrogenase (ACE) inhibitors. Tyr-transferase (NADP+) kinase inhibitors, (isocitrate dehydrogenase (NADP+)) kinase inhibitors, (tyrosine 3-monooxygenase) kinase inhibitors, myosin heavy chain inhibitors, Fas-activated serine / threonine kinase inhibitors, Goodpasture's antigen-binding protein kinase inhibitors, IκB kinase inhibitors, cAMP-dependent protein kinase (or protein kinase A, PKA) inhibitors, cGMP-dependent protein kinase (or protein kinase G, PKG) inhibitors, protein kinase B (PKB) inhibitors, protein kinase C (PKC) inhibitors, rhodopsin kinase inhibitors, β-adrenergic receptor kinase inhibitors, G protein-coupled receptor kinase inhibitors, Ca 2+ / Calmodulin-dependent (CaM) kinase (CAMK) inhibitors, myosin light chain kinase inhibitors, phosphorylase kinase inhibitors, and elongation factor 2 kinase inhibitors. Two exemplary RSTK inhibitors are Rho-associated protein kinase (ROCK) kinase inhibitors, including ROCK1 inhibitors and ROCK2 inhibitors, and MAPK kinase inhibitors, including MAPK1 inhibitors, MAPK3 inhibitors, MAPK4 inhibitors, MAPK6 inhibitors, MAPK7 inhibitors, MAPK8 inhibitors, MAPK9 inhibitors, MAPK10 inhibitors, MAPK11 inhibitors, MAPK12 inhibitors, MAPK13 inhibitors, MAPK14 inhibitors, and MAPK15 inhibitors.

[0049] The therapeutic compound disclosed herein may be a poly ADP ribose polymerase (PARP) inhibitor. PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). PARP inhibitors are used to treat cancer and are considered as potential treatments for acute life-threatening diseases such as stroke and myocardial infarction, as well as long-term neurodegenerative diseases. In some embodiments, the PARP inhibitor is a PARP1 inhibitor or a PARP2 inhibitor. Non-limiting examples of PARP inhibitors are iniparib, olaparib, niraparib, rucaparib, talazoparib, and veliparib.

[0050] In one embodiment, the pharmaceutical compositions disclosed herein comprise one or more therapeutic compounds 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, the pharmaceutical compositions disclosed herein comprise one or more therapeutic compounds 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 therapeutic compounds in an amount, e.g., up to 0.05%, up to 0.1%, up to 1%, up to 2.5%, up to 5%, up to 7.5%, up to 10%, up to 12.5%, up to 15%, up to 17.5%, up to 20%, up to 22.5%, up to 25%, up to 30%, up to 35%, up to 40%, up to 45%, or up to 50% (by weight).

[0051] In one embodiment, the pharmaceutical composition disclosed herein may be administered in a concentration 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 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% ~ about 7.5%, about 0.1% to about 10%, about 0.1% to about 12.5%, about 0.1% to about 15%, about 0.1% to about 17.5%, about 0.1% to about 20%, about 0.1% to about 22.5%, about 0.1% to about 25%, about 0.1% to about 30%, about 0.1% to about 40%, about 0.1% to about 50%, about 1% to about 2.5%, about 1% to about 5%, about 1% to about 7.5%, about 1% to about 10%, about 1% to about 12.5%, about 1% to about 15%, about 1% to about 17.5%, about 1% to about 20%, about 1% to about 22.5%, about 1% to about 25%, about 1% to about 30%, about 1% to about 40%, about 1% ~ about 50%, about 5% to about 10%, about 5% to about 20%, about 5% to about 30%, about 5% to about 40%, about 5% to about 50%, about 5% to about 60%, about 5% to about 70%, about 5% to about 80%, about 5% to about 90%, 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 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 30% 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 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 50% to about 60%, about 50% to about 70%, about 50% to about 80%, about 50% to about 90%, about 60% to about 70%, about 60% to about 80%, about 60% to about 90%, about 70% to about 80%, about 70% to about 90%, or about 80% to about 90% (by weight) of one or more therapeutic compounds disclosed herein.

[0052] In one embodiment, the pharmaceutical compositions disclosed herein include, for example, 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 300 mg / mL, about 350 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 350 mg / mL, about 350 mg / mL, about 400 mg / mL, about 450 mg / mL, about 500 mg / mL, about 550 mg / mL, about 600 mg / mL, about 650 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 ... g / mL, about 250 mg / mL, about 275 mg / mL, about 300 mg / mL, about 325 mg / mL, about 350 mg / mL, about 375 mg / mL, about 400 mg / mL, about 425 mg / mL, about 450 mg / mL, about 475 mg / mL, about 500 mg / mL, about 525 mg / mL, about 550 mg / mL, about 575 mg / mL, or about 600 mg / mL. In one embodiment, the pharmaceutical compositions disclosed herein comprise, for example, 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 22 mg / mL, at least 26 mg / mL, at least 28 mg / mL, at least 32 mg / mL, at least 36 mg / mL, at least 38 mg / mL, at least 39 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 22 mg / mL, at least 36 mg / mL, at least 38 mg / mL, at least 40 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 22 mg / mL, at least 40 mg / mL, at least 40 mg / mL, at least 40 Contains one or more therapeutic compounds at a concentration of 5 mg / mL, at least 250 mg / mL, at least 275 mg / mL, at least 300 mg / mL, at least 325 mg / mL, at least 350 mg / mL, at least 375 mg / mL, at least 400 mg / mL, at least 425 mg / mL, at least 450 mg / mL, at least 475 mg / mL, at least 500 mg / mL, at least 525 mg / mL, at least 550 mg / mL, at least 575 mg / mL, or at least 600 mg / mL.In one embodiment, the pharmaceutical compositions disclosed herein may be administered at any concentration, e.g., up to 25 mg / mL, up to 30 mg / mL, up to 35 mg / mL, up to 40 mg / mL, up to 45 mg / mL, up to 50 mg / mL, up to 60 mg / mL, up to 65 mg / mL, up to 70 mg / mL, up to 75 mg / mL, up to 100 mg / mL, up to 125 mg / mL, up to 150 mg / mL, up to 175 mg / mL, up to 200 mg / mL, up to 225 mg / mL, g / mL, up to 250 mg / mL, up to 275 mg / mL, up to 300 mg / mL, up to 325 mg / mL, up to 350 mg / mL, up to 375 mg / mL, up to 400 mg / mL, up to 425 mg / mL, up to 450 mg / mL, up to 475 mg / mL, up to 500 mg / mL, up to 525 mg / mL, up to 550 mg / mL, up to 575 mg / mL, or up to 600 mg / mL.

[0053] In one embodiment, the pharmaceutical composition disclosed herein may be, for example, 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 25 mg / mL to about 350 mg / mL, about 25 mg / mL to about 400 mg / mL, about 25 mg / mL to about 450 mg / mL, about 25 mg / mL to about 5 00mg / mL, about 25mg / mL to about 550mg / mL, about 25mg / mL to about 600mg / mL, about 50mg / mL to about 100mg / mL, about 50mg / mL to about 150mg / mL, about 50mg / mL to about 200mg / mL, about 50mg / mL to about 250mg / mL, about 5 0mg / mL to about 300mg / mL, about 50mg / mL to about 350mg / mL, about 50mg / mL to about 400mg / mL, about 50mg / mL to about 450mg / mL, about 50mg / mL to about 500mg / mL, about 50mg / mL to about 550mg / mL, about 50mg / mL to about 60 0mg / mL, about 75mg / mL to about 100mg / mL, about 75mg / mL to about 150mg / mL, about 75mg / mL to about 200mg / mL, about 75mg / mL to about 250mg / mL, about 75mg / mL to about 300mg / mL, about 75mg / mL to about 350mg / mL, about 75 mg / mL~about 400mg / mL, about 75mg / mL~about 450mg / mL, about 75mg / mL~about 500mg / mL, about 75mg / mL~about 550mg / mL, about 75mg / mL~about 600mg / mL, about 100mg / mL~about 150mg / mL, about 100mg / mL~about 2 00mg / mL, about 100mg / mL to about 250mg / mL, about 100mg / mL to about 300mg / mL, about 100mg / mL to about 350mg / mL, about 100mg / mL to about 400mg / mL, about 100mg / mL to about 450mg / mL, about 100mg / mL to about 500mg / mL, about 100mg / mL to about 550mg / mL, about 100mg / mL to about 600mg / mL, about 150mg / mL to about 200mg / mL, about 150mg / mL to about 250mg / mL, about 150mg / mL to about 300mg / mL, about 150mg / mL to about 350mg / mL,Approximately 150mg / mL to approximately 400mg / mL, approximately 150mg / mL to approximately 450mg / mL, approximately 150mg / mL to approximately 500mg / mL, approximately 150mg / mL to approximately 550mg / mL, approximately 150mg / mL to approximately 600mg / mL, approximately 200m g / mL~about 250mg / mL, about 200mg / mL~about 300mg / mL, about 200mg / mL~about 350mg / mL, about 200mg / mL~about 400mg / mL, about 200mg / mL~about 450mg / mL, about 200mg / mL~ Approx. 500mg / mL, Approx. 200mg / mL~Approx. 550mg / mL, Approx. 200mg / mL~Approx. 600mg / mL, Approx. 250mg / mL~Approx. 300mg / mL, Approx. 250mg / mL~Approx. 350mg / mL, Approx. 250mg / mL~Approx. 400m g / mL, about 250 mg / mL to about 450 mg / mL, about 250 mg / mL to about 500 mg / mL, about 250 mg / mL to about 550 mg / mL, about 250 mg / mL to about 600 mg / mL, about 300 mg / mL to about 350 mg / mL, Approximately 300mg / mL to approximately 400mg / mL, approximately 300mg / mL to approximately 450mg / mL, approximately 300mg / mL to approximately 500mg / mL, approximately 300mg / mL to approximately 550mg / mL, approximately 300mg / mL to approximately 600mg / mL, approximately 350m g / mL~about 400mg / mL, about 350mg / mL~about 450mg / mL, about 350mg / mL~about 500mg / mL, about 350mg / mL~about 550mg / mL, about 350mg / mL~about 600mg / mL, about 400mg / mL~ The therapeutic compound may include one or more therapeutic compounds having a concentration of about 450 mg / mL, about 400 mg / mL to about 500 mg / mL, about 400 mg / mL to about 550 mg / mL, about 400 mg / mL to about 600 mg / mL, about 450 mg / mL to about 500 mg / mL, about 450 mg / mL to about 550 mg / mL, about 450 mg / mL to about 600 mg / mL, about 500 mg / mL to about 550 mg / mL, about 500 mg / mL to about 600 mg / mL, and about 550 mg / mL to about 600 mg / mL.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[0077] In some embodiments, a pharmaceutical composition disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount of, for example, about 10% (by weight), about 15% (by weight), about 20% (by weight), about 25% (by weight), about 30% (by weight), about 35% (by weight), about 40% (by weight), about 45% (by weight), about 50% (by weight), about 55% (by weight), about 60% (by weight), about 65% (by weight), about 70% (by weight), or about 75% (by weight). In some embodiments, a pharmaceutical composition disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount 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, a pharmaceutical composition disclosed herein may comprise one or more liquid fats or glycerolipids that are liquid at 18° C., comprising, consisting essentially of, or consisting of one or more monoglycerides in an amount 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).

[0078] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration 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 25%, about 15% to about 30%, about 15% to about 35%, about 15% to about 40%, about 15% to about 45%, about 15% to about 50%, about 15% to about 55%, About 15% to about 60%, about 15% to about 65%, about 15% to about 70%, about 20% to about 25%, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 20% to about 65%, about 20% to about 70%, about 25% to about 30%, about 25% to about 35%, about 25% to about 40%, about 25% to about 45%, about 25% to about 50%, about 25% to about 55%, about 25% to about 60%, about 25% to about 65%, about 25% to about 70%, about 30% ~ about 35%, about 30% to about 40%, about 30% to about 45%, about 30% to about 50%, about 30% to about 55%, about 30% to about 60%, about 30% to about 65%, about 30% to about 70%, about 35% to about 40%, about 35% to about 45%, about 35% to about 50%, about 35% to about 55%, about 35% to about 60%, about 35% to about 65%, about 35% to about 70%, about 40% to about 45%, about 40% to about 50%, about 40% to about 55%, about 40% to about 60%, about 40% to about 65%, about 40% to about 70%, about 45% to about 50%, about 45% to about 5 The composition may comprise one or more liquid fats or glycerolipids that are liquid at 18° C. and that comprise, consist essentially of, or consist of one or more monoglycerides in an amount of about 5%, 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% (by weight).

[0079] Commercially available hard fats or glycerolipids that are solid at 18°C ​​include cocoa butter, saturated C fat with a melting point of about 33°C, 10 -C18 A mixture of triglycerides (GELUCIRE® 33 / 01), a saturated C 10 -C 18 A mixture of triglycerides (GELUCIRE® 39 / 01) and saturated C 10 -C 18 Commercially available liquid fats or glycerolipids that are liquid at 18° C. include, but are not limited to, mixtures of triglycerides (GELUCIRE® 43 / 01), and include, but are not limited to, hydrolyzed corn oil with glycerol monolinoleate (MAISINE™ 35-1, MAISINE™ CC). In some embodiments, hydrolyzed corn oil with glycerol monolinoleate (MAISINE™ 35-1, MAISINE™ CC) contains about 32%-52% monoglycerides, about 40%-50% diglycerides, and about 5%-30% triglycerides, including glycerol monolinoleate.

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

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

[0082] Digestive aid The pharmaceutical compositions disclosed herein may include one or more digestive enhancers. The primary purpose of the one or more digestive enhancers is to increase the solubility of the therapeutic compounds disclosed herein with the glycerolipid mixture, to increase the absorption of the therapeutic compounds disclosed herein, thereby improving the pharmacokinetics of the compounds, and / or to improve the availability of the therapeutic compounds disclosed herein, promote the selected biodistribution, thereby improving the pharmacodynamics of the compounds. These improved properties are achieved by the one or more digestive enhancers by creating a pre-lipid digestion formulation of the therapeutic compounds disclosed herein, which promotes and enhances the processing of one or more glycerolipids disclosed herein once the pharmaceutical compositions disclosed herein enter the duodenal region of the small intestine. Such glycerolipid processing allows one or more therapeutic compounds included in the pharmaceutical composition to be absorbed by the absorptive epithelial cells along with the digested glycerolipids, and subsequently processed and transported to the lymphatic system. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers including one or more bile acids. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers including cholic acid. In some embodiments, the disclosed pharmaceutical compositions include one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions include one or more C14 -C 20 In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers comprising free fatty acids. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers comprising oleic acid, steric acid, or linoleic acid. In some embodiments, the disclosed pharmaceutical compositions include one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions include one or more C 14 -C 20 The pharmaceutical compositions disclosed herein include one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the pharmaceutical compositions disclosed herein include one or more digestive enhancers, including sodium oleate, sodium stearate, and / or sodium linoleate.

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

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

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

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

[0087] In some embodiments, the disclosed pharmaceutical compositions comprise 1) one or more bile acids disclosed herein; 2) one or more C 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers, including 1) one or more bile acids disclosed herein, 2) one or more C2H3O4, 2H4O5, 2H5O6, 2H6O7, 2H8O, 2H9O, 2H10O, 2H11O, 2H12O, 2H2O, 2H3O, 2H4O, 2H5O, 2H6O, 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions comprise one or more digestive enhancers comprising 1) cholic acid as disclosed herein, 2) oleic acid, steric acid, and / or linoleic acid, and 3) one or more phospholipids as disclosed herein.

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

[0089] In some embodiments, the disclosed pharmaceutical compositions comprise: 1) one or more of the Cs disclosed herein. 14 -C 24 1) one or more C phospholipids disclosed herein; and 2) one or more C phospholipids disclosed herein. 14 -C 24 In some embodiments, the disclosed pharmaceutical compositions include one or more of the C10-11000-stimulants disclosed herein. 14 -C 20 1) one or more C phospholipids disclosed herein; and 2) one or more C phospholipids disclosed herein. 14 -C 20 In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers, including free fatty acid surfactants. In some embodiments, the disclosed pharmaceutical compositions include one or more of 1) oleic acid, steric acid, and / or linoleic acid, 2) one or more phospholipids disclosed herein, and 3) one or more C phospholipids disclosed herein. 14 -C 20 and one or more digestive enhancers including free fatty acid sodium surfactants. In some embodiments, the disclosed pharmaceutical compositions include one or more digestive enhancers including 1) oleic acid, steric acid, and / or linoleic acid, 2) one or more phospholipids disclosed herein, and 3) sodium oleate, sodium stearate, and / or sodium linoleate.

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

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

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

[0093] bile acids The pharmaceutical compositions disclosed herein may include one or more bile acids. The main purpose of the bile acids is to increase the solubility of the therapeutic compounds disclosed herein in the glycerolipid mixture, to increase the absorption of the therapeutic compounds disclosed herein, thereby improving the pharmacokinetics of the compounds, and / or to improve the availability of the therapeutic compounds disclosed herein, to promote the selected biodistribution, thereby improving the pharmacodynamics of the compounds. Furthermore, as disclosed in Example 2, the bile acids disclosed herein may be combined with one or more glycerolipids and / or one or more free C2H3-binding domains disclosed herein. 14-24 Improves the solubility of the therapeutic compounds disclosed herein in fatty acids. Improved solubility properties are achieved by bile acids by preventing recrystallization of the therapeutic compounds during solidification when the molton pharmaceutical composition is cooled to room temperature (18°C-20°C). Improved pharmacokinetic properties are achieved by bile acids by breaking down the lipid components of the pharmaceutical compositions disclosed herein through their surfactant properties into smaller lipid structures that mimic emulsion droplets, thereby facilitating the emulsification process. The "emulsion droplets" recruit coliapses, creating a larger surface area where pancreatic lipase can digest the hard fatty glycerolipids present therein, ultimately facilitating absorption in the absorptive epithelial cells and subsequent chylomicron formation. Bile acids are involved in signaling for the initiation of chylomicron formation. Thus, inclusion of bile acids in the lipid formulation maximizes this signaling pathway and the production of chylomicrons, and the resulting improved pharmacodynamic properties offered by bile acids are brought about by increasing the availability of the therapeutic compound by increasing its content within chylomicrons before entering the circulatory system, and subsequently facilitating its delivery to compartments such as the brain across membranes such as the blood-brain barrier and the choroid plexus.

[0094] Bile acids, amphiphilic molecules with an HLB greater than 12, have a specific chemical structure that differs from ordinary aliphatic surfactants due to the presence of a large, rigid, flat, hydrophobic portion of the steroid nucleus with 2-4 hydroxyl groups. Specifically, bile acids contain the following basic components: (1) four rings, (2) a 5- / 8-carbon side chain terminating in a carboxylic acid, and (3) several hydroxyl groups (the position / number of which varies among the various salts). The rings are ascribed letters A, B, C, and D based on their distance from the side chain bearing the -COOH group, with the D ring being the furthest away (and 1 C smaller than the other rings), as explained below. The β-hydroxyl group points up / out, the α-group points down, and all bile acids have a 3-hydroxyl group derived from their cholesterol precursor. The chemical structure of the bile salts makes this emulsification route useful according to the teachings of the present disclosure, and thus synthetic surfactants do not work.

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

[0096] There is a direct correlation between the amount of bile acid present in the pharmaceutical compositions disclosed herein and the improved properties observed. Thus, the more bile acid present in the pharmaceutical compositions disclosed herein, the greater the improvement in solubility, absorption, and availability of the therapeutic composition. Furthermore, the upper limit of bile acid included in the pharmaceutical compositions disclosed herein is not limited to the solubility point of the bile acid. Thus, the pharmaceutical compositions disclosed herein may include a supersaturated amount of bile acid. Thus, the upper limit of bile acid that may be included in the pharmaceutical compositions disclosed herein is its critical micelle concentration (CMC). In addition to the improved properties mentioned above, a further advantage of a supersaturated amount of bile acid is the presence of the resulting nanoparticle formation of crystalline bile acid in the pharmaceutical compositions disclosed herein. Without wishing to be limited by one theory, bile acid nanoparticles dissolve when exposed to the alkaline environment of the small intestine to form bile salts, which can act as a reservoir that further promotes the emulsification process of the pharmaceutical compositions disclosed herein.

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

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

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

[0100] C 14-24 fatty acid The pharmaceutical compositions disclosed herein contain one or more free C 14-24 The fatty acids may include carboxylic acids with long unbranched hydrocarbon chains that may be saturated or unsaturated and are hydrophobic molecules with an HLB of less than 4. 14-24 The primary purpose of the fatty acids is to increase the solubility of the therapeutic compounds disclosed herein in the glycerolipid mixture and to increase the absorption of the therapeutic compounds disclosed herein, thereby improving the pharmacokinetics of the compounds. The improved solubility properties are due to their property of being a solvent that promotes the dissolution of the therapeutic compounds disclosed herein, and the free C 14-24 The improved absorption properties are achieved by promoting and increasing the formation of micelles by breaking up larger emulsion droplets, thereby mimicking the lipid digestion products of triglycerides, i.e. free fatty acids, which are then absorbed by the free C 14-24 This is achieved by the fatty acids disclosed herein. 14-24Fatty acids increase the uptake of micelles containing one or more therapeutic compounds into absorptive 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.

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

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

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

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

[0105] Free C useful in the pharmaceutical compositions disclosed herein 14-24The amount of fatty acid is an amount that does not adversely affect the pharmacokinetics of the therapeutic compound with which it is formulated. In some embodiments, the pharmaceutical compositions disclosed herein contain one or more free C 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 35% (by weight), about 30% (by weight), about 40% (by weight), about 50% (by weight), about 60% (by weight), about 70% (by weight), or about 75% (by weight). 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein may comprise one or more free C in an amount of, for example, at least 1% (by weight), at least 2.5% (by weight), at least 5% (by weight), at least 7.5% (by weight), at least 10% (by weight), at least 12.5% ​​(by weight), at least 15% (by weight), at least 17.5% (by weight), at least 20% (by weight), at least 22.5% (by weight), at least 25% (by weight), at least 30% (by weight), at least 35% (by weight), at least 40% (by weight), at least 50% (by weight), at least 60% (by weight), at least 70% (by weight), or at least 75% (by weight). 14-24In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acids. In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of fatty acids. 14-24 It may comprise, consist essentially of, or consist of fatty acids.

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

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

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

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

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

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

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

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

[0114] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 1.0% to about 2.0%, about 1.0% to about 3.0%, about 1.0% to about 4.0%, about 1.0% to about 5.0%, about 1.0% to about 6.0%, about 1.0% to about 7.0%, about 1.0% to about 8.0%, about 1.0% to about 9.0%, about 1.0% to about 10.0%, about 2.0% to about 3.0%, about 2.0% to about 4.0%, about 2.0% to about 5.0%, about 2.0% to about 6.0%, about 2.0% to about 7.0%, about 2.0% to about 8.0%, about 2.0% to about 9.0%, about 2.0% to about 10.0%, about 3.0% to about 4.0%, about 3.0% to about 5.0%, about 3.0% to about 6.0%, about 3.0% to about 7.0%, about 3.0% to about 8.0%, about 3.0% to about 9.0%, about 3.0% to about 10.0% , about 4.0% to about 5.0%, about 4.0% to about 6.0%, about 4.0% to about 7.0%, about 4.0% to about 8.0%, about 4.0% to about 9.0%, about 4.0% to about 10.0%, about 5.0% to about 6.0%, about 5.0% to about 7.0%, 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. It may comprise, consist essentially of, or consist of one or more phospholipids in an amount of 0% to about 9.0%, about 6.0% to about 10.0%, about 7.0% to about 8.0%, about 7.0% to about 9.0%, about 7.0% to about 10.0%, about 8.0% to about 9.0%, about 8.0% to about 10.0%, or about 9.0% to about 10.0% (by weight).

[0115] C 14-24 Fatty Acid Surfactant The pharmaceutical compositions disclosed herein contain one or more free C 14-24 The surfactants may include fatty acid surfactants. Fatty acid surfactants include carboxylic acids with long unbranched hydrocarbon chains that may be either saturated or unsaturated associated with an alkali metal or other metal ion, and are hydrophobic amphiphilic molecules with an HLB greater than 12. One or more free C 14-24The primary purpose of the fatty acid surfactant is to enhance the solubility of the therapeutic compounds disclosed herein with the glycerolipid mixture and to enhance the absorption of the therapeutic compounds disclosed herein, thereby improving the pharmacokinetics of the compounds. The improved solubility properties are achieved by increasing the amount of one or more free C 14-24 This is achieved by the fatty acid surfactant through the interaction of its carboxylic acid functional group with the sodium ion present on the therapeutic compound, which neutralizes the charge and facilitates compound interaction with the hydrophobic glycolipid mixture. 14-24 The amount of fatty acid surfactant is sufficient to displace the salt from the therapeutic compound and have the salt replaced by the fatty acid as a counterion to form the therapeutic compound solubilized in the lipid matrix. 14-24 The fatty acid surfactant is calculated to be at a minimum stoichiometric or superstoichiometric concentration to ensure that the fatty acid surfactant is present. In the case of free base therapeutic compounds, it can be at a sub- or superstoichiometric concentration since the fatty acid surfactant also acts as a solubilizer of the therapeutic compound in the composition and does not act as a counterion. The improved absorption properties are due to the fact that it promotes and increases the formation of mixed micelles by breaking up larger emulsion droplets, thereby mimicking the lipid digestion products of triglycerides, i.e., free fatty acids, which are the free C 14-24 This is achieved by the fatty acid surfactant. 14-24 The fatty acid surfactant increases the uptake of micelles containing one or more therapeutic compounds into absorptive epithelial cells. 14-24 The fatty acid surfactants are free C in combination with alkali metals, e.g., lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), and francium (Fr), or alkaline earth metals, e.g., beryllium (Be), magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba), and radium (Ra). 14-24 It is a fatty acid.

[0116] In some embodiments, the pharmaceutical compositions disclosed herein comprise an unsaturated free C14 -C 16 Fatty acid surfactant, unsaturated free C 14 -C 18 Fatty acid surfactant, unsaturated free C 14 -C 20 Fatty acid surfactant, unsaturated free C 14 -C 22 Fatty acid surfactant, unsaturated free C 14 -C 24 Fatty acid surfactant, unsaturated free C 16 -C 18 Fatty acid surfactant, unsaturated free C 16 -C 20 Fatty acid surfactant, unsaturated free C 16 -C 22 Fatty acid surfactant, unsaturated free C 16 -C 24 Fatty acid surfactant, unsaturated free C 18 -C 20 Fatty acid surfactant, unsaturated free C 18 -C 22 Fatty acid surfactant, unsaturated free C 18 -C 24 Fatty acid surfactant, unsaturated free C 20 -C 22 Fatty acid surfactant, or unsaturated free C 22 -C 24 One or more free Cs comprising, consisting essentially of, or consisting of fatty acid surfactants 14-24 In some embodiments, the pharmaceutical compositions disclosed herein may include a fatty acid surfactant. 18 -C 22 Fatty acid surfactant, ω-5 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-6 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-7 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-9 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-10 unsaturated free C 18 -C 22 Fatty acid surfactant, ω-11 unsaturated free C 18 -C22 Fatty acid surfactant, or ω-12 unsaturated free C 18 -C 22 One or more free Cs comprising, consisting essentially of, or consisting of fatty acid surfactants 14-24 A fatty acid surfactant may also be included.

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

[0118] In some embodiments, the pharmaceutical compositions disclosed herein comprise saturated and unsaturated free C 14 -C 16 Mixture of fatty acid surfactants, saturated and unsaturated free C14 -C 18 Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 20 Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 22 Mixture of fatty acid surfactants, saturated and unsaturated free C 14 -C 24 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 18 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 20 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 22 Mixture of fatty acid surfactants, saturated and unsaturated free C 16 -C 24 Mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 20 Mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 22 Mixture of fatty acid surfactants, saturated and unsaturated free C 18 -C 24 Mixture of fatty acid surfactants, saturated and unsaturated free C 20 -C 22 Mixture of fatty acid surfactants, or saturated and unsaturated free C 22 -C 24 One or more free C surfactants comprising, consisting essentially of, or consisting of a mixture of fatty acid surfactants. 14-24 A fatty acid surfactant may also be included.

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

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

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

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

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

[0124] Curcumin Aspects of the present specification partially disclose curcumin. In some embodiments, the pharmaceutical compositions disclosed herein may include curcumin. Curcumin is a phenolic pigment extracted from turmeric. Despite being a pharmacologically bioactive molecule, curcumin can promote gallbladder contraction, making this compound useful as a digestive enhancer disclosed herein. Gallbladder contraction is a key process in fat absorption, thus providing an important benefit of increasing the formation of mixed micelles by breaking up larger emulsion droplets, thereby increasing the uptake of micelles containing one or more therapeutic compounds into absorptive epithelial cells. Although a highly insoluble compound, curcumin is soluble using the formulations disclosed herein.

[0125] The amount of curcumin useful in the pharmaceutical compositions disclosed herein is a therapeutically effective amount or an amount effective for promoting gallbladder contraction.In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of, for example, about 0.1%, about 0.5%, about 1% (by weight), about 1.5% (by weight), about 2% (by weight), about 2.5% (by weight), about 3% (by weight), about 4% (by weight), about 5% (by weight), about 7.5% (by weight), or about 10% (by weight) of curcumin. In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of curcumin in an amount, e.g., at least 0.1%, at least 0.5%, at least 1% (by weight), at least 1.5% (by weight), at least 2% (by weight), at least 2.5% (by weight), at least 3% (by weight), at least 4% (by weight), at least 5% (by weight), at least 7.5% (by weight), or at least 10% (by weight). In some embodiments, the pharmaceutical compositions disclosed herein may comprise, consist essentially of, or consist of curcumin in an amount, e.g., up to 0.1%, up to 0.5%, up to 1% (by weight), up to 1.5% (by weight), up to 2% (by weight), up to 1% (by weight), up to 1.5% (by weight), up to 2% (by weight), up to 2.5% (by weight), up to 3% (by weight), up to 4% (by weight), up to 5% (by weight), up to 7.5% (by weight), or up to 10% (by weight).

[0126] In some embodiments, the pharmaceutical compositions disclosed herein may be administered in a concentration of, for example, about 0.1% to about 1% (by weight), about 0.1% to about 1.5% (by weight), about 0.1% to about 2% (by weight), about 0.1% to about 2.5% (by weight), about 0.1% to about 5% (by weight), about 0.1% to about 7.5% (by weight), about 0.1% to about 10% (by weight), about 0.5% to about 1% (by weight), about 0.5% to about 1.5% (by weight), about 0.5% to about 2% (by weight), about 0.5% to about It may comprise, consist essentially of, or consist of curcumin in an amount of about 2.5% (by weight), about 0.5% to about 5% (by weight), about 0.5% to about 7.5% (by weight), about 0.5% to about 10% (by weight), about 1% to about 1.5% (by weight), about 1% to about 2% (by weight), about 1% to about 2.5% (by weight), about 1% to about 5% (by weight), about 1% to about 7.5% (by weight), or about 1% to about 10% (by weight).

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

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

[0129] The stabilizer disclosed herein is not a solvent because it is used in an amount that does not result in substantial dissolution of the solute. Thus, the amount of stabilizer used in the solid solution composition disclosed herein results in 85% or less dissolution of the therapeutic compound disclosed herein. In an aspect of this embodiment, the amount of stabilizer used in the solid solution composition disclosed herein results in, for example, 80% or less, 75% or less, 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, or 5% or less dissolution of the therapeutic compound disclosed herein.

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

[0131] PEG polymers include PEG100, PEG200, PEG300, PEG400, PEG500, PEG600, PEG700, PEG800, PEG900, PEG1000, PEG1100, PEG1200, PEG1300, PEG1400, PEG1500, PEG1600, PEG1700, PEG1800, PEG1900, PEG2000, PEG2100, PEG2200, PEG2300, PEG2400, PEG2500, PEG2600, PEG2700, PEG2800, PEG2900, PEG3000, PEG3250, PEG3350, Examples of suitable PEG-10,100, PEG-20,100, PEG-30,100, PEG-40,100, PEG-50,100, PEG-60,100, PEG-70,100, PEG-80,100, PEG-90,100, PEG-110,100, PEG-120,100, PEG-130,100, PEG-140,100, PEG-150,100, PEG-160,100, PEG-170,100, PEG-180,100, PEG-190,100, or PEG-200,100.

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

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

[0134] In some embodiments, the pharmaceutical compositions disclosed herein do not 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.

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

[0136] In still other aspects of this embodiment, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 60%, about 10% to about 70%, about 10% to about 80%, about 10% to about 90%, about 10% to about 100%, about 20% 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 30% to about 40%, about 30% to about 50%, about 40% to about 60%, about 40% to about 70%, about 40% to about 80%, about 40% to about 90%, about 50% to about 10 ... % to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 20% to about 80%, about 20% to about 90%, about 20% to about 100%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%, about 30% to about 80%, about 30% to about 90%, about 30% to approx. 100%, approx. 40% to approx. 50%, approx. 40% to approx. 60%, approx. 40% to approx. 70%, approx. 40% to approx. 80%, approx. 40% to approx. 90%, approx. 40% to approx. 100%, approx. 50% to approx. 60%, approx. 50% to approx. 70%, approx. 50% to approx. 80%, approx. 50% to approx. 90%, approx. 50% to approx. 100%, approx. 60% to approx. 70%, approx. 60% to approx. 80%, about 60% to about 90%, about 60% to about 100%, about 70% to about 80%, about 70% to about 90%, about 70% to about 100%, about 80% to about 90%, about 80% to about 100%, or about 90% to about 100% is delivered to or enters the lipid digestion and / or absorption pathways.

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

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

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

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

[0141] Examples 3-6 illustrate therapeutic compounds formulated according to this process.

[0142] Methods and Uses Aspects of the present specification, in part, disclose a method of treating an individual having a disease or disorder. In one embodiment, the method comprises administering a pharmaceutical composition disclosed herein to an individual in need thereof, where the administration reduces symptoms associated with the disease or disorder, thereby treating the individual. Aspects of the present specification, in part, disclose a pharmaceutical composition disclosed herein for use in treating a disease or disorder. Aspects of the present specification, in part, disclose a use of a pharmaceutical composition disclosed herein for treating a disease or disorder. Aspects of the present specification, in part, disclose a use of a pharmaceutical composition disclosed herein in the manufacture of a medicament for treating a disease or disorder. Diseases or disorders disclosed herein include, but are not limited to, neoplasms, cancer, inflammation, autoimmune disorders, idiopathic pulmonary fibrosis, and renal disease or disorder. Because the pharmaceutical compositions disclosed herein rely on the digestive process of the gastrointestinal tract, oral administration is the preferred route of administration.

[0143] Aspects of the present specification disclose, in part, treating an individual suffering from a disease or disorder. As used herein, the term "treat" refers to reducing or eliminating the clinical symptoms of a disease or disorder in an individual, or delaying or preventing the onset of the clinical symptoms of a disease or disorder in an individual. For example, the term "treat" can mean reducing the symptoms of a condition characterized by a disease or disorder, for example, by 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 a disease or disorder are well known and can be determined by those skilled in the art by considering factors including, but not limited to, the location of the disease or disorder, the cause of the disease or disorder, the severity of the disease or disorder, and / or the tissue or organ affected by the disease or disorder. One of ordinary skill in the art will know the appropriate symptoms or indicators associated with a particular type of disease or disorder, and will know how to determine whether an individual is a candidate for the treatments disclosed herein.

[0144] Aspects of the present specification partially disclose diseases or disorders that are neoplasms. Neoplasms can be divided into four main groups: benign neoplasms, intraepithelial neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Neoplasms can be benign, potentially malignant, or malignant (i.e., cancer). Benign neoplasms include uterine fibroids, bone spurs, and pigmented nevi (skin moles). Potentially malignant neoplasms are localized and do not invade or destroy surrounding tissues, but have the potential to transform into malignant neoplasms. Potentially malignant neoplasms include intraepithelial carcinomas. Malignant neoplasms are commonly referred to as cancers. They can invade and destroy surrounding tissues, metastasize, and generally prove fatal if untreated or unresponsive to treatment. Secondary neoplasms refer to any of a class of cancers that are either metastatic derivatives of a primary tumor, or apparently unrelated tumors that increase in frequency after certain cancer treatments, such as chemotherapy or radiation therapy. Rarely, there can be metastatic neoplasms where the site of the primary cancer is not known and this is classified as cancer of unknown primary.

[0145] Aspects of the present specification partially disclose a disease or disorder that is cancer. Cancer or malignant neoplasms are a large group of diseases involving uncontrolled growth and division of abnormal cells. Cancer can be a primary cancer, an initial or original malignant neoplastic disease, or a metastatic cancer, a malignant neoplasm derived from a primary cancer that spreads or invades other parts of the body and causes a new malignant neoplasm. Cancer can be a solid tumor, which contains an abnormal tissue mass that usually does not contain cysts or liquid areas, or a non-solid (blood) tumor, a malignant neoplasm that lacks a mass.

[0146] Cancers are classified according to the type of cells that the tumor cells resemble and are therefore presumed to be the origin of the tumor. These types include carcinomas, sarcomas, lymphomas and leukemias, germ cell tumors, and blastomas. Carcinomas are malignant tumors that arise from epithelial cells, including the epithelial lining that covers the surfaces of internal organs and glands. This group includes many of the most common cancers, including almost all cancers in the bladder, brain, breast, cervix, colon, endometrium, kidney, liver, lung, ovary, pancreas prostate, rectum, skin, small intestine, stomach, thyroid, and uterus. Sarcomas are malignant tumors that arise from mesenchymal cells, including neoplasms derived from connective tissues such as bone, cartilage, fat, nerve, and vascular tissue, while lymphomas or leukemias are malignant tumors that arise from hematopoietic (blood-forming) cells that tend to leave the bone marrow and mature in lymph nodes (lymphomas) and blood (leukemias). Germ cell tumors are malignant tumors that arise from pluripotent cells and are most often located in the testes or ovaries (seminomas and dysgerminomas, respectively). Blastomas are malignant tumors that arise from immature "precursor" cells or embryonic tissue.

[0147] Non-limiting examples of cancers include basal cell skin cancer, bladder cancer, brain cancer, breast cancer, cervical cancer, colon cancer, endometrial cancer, glioblastoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, kidney cancer, leukemia, lip cancer, liver cancer, lymphoma, melanoma, mesothelioma, myeloma, non-small cell lung cancer, non-melanoma skin cancer, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, sarcoma, small cell lung cancer, squamous cell skin cancer, and thyroid cancer, whether primary or metastatic.

[0148] In aspects of this embodiment, the cancer includes bone or muscle cancer, including but not limited to chondrosarcoma, Ewing's sarcoma, malignant fibrous histiocytoma, osteosarcoma, rhabdomyosarcoma, and cardiac cancer.

[0149] In aspects of this embodiment, cancer includes brain or nerve cancers, including but not limited to astrocytoma, brain stem glioma, pilocytic astrocytoma, ependymoma, primitive neuroectodermal tumor, cerebellar astrocytoma, cerebral astrocytoma, glioblastoma, glioma, medulloblastoma, neuroblastoma, oligodendroglioma, pineal astrocytoma, pituitary adenoma, and hypothalamic glioma.

[0150] In aspects of this embodiment, cancer includes breast cancer, including but not limited to female breast cancer, invasive cribriform carcinoma, invasive lobular carcinoma, medullary carcinoma, male breast cancer, phyllodes tumor, and tubular carcinoma.

[0151] In aspects of this embodiment, the cancer includes endocrine cancers, including but not limited to adrenocortical carcinoma, islet cell carcinoma (endocrine pancreas), Merkel cell carcinoma, multiple endocrine neoplasia syndrome, parathyroid cancer, pheochromocytoma, and thyroid cancer.

[0152] In aspects of this embodiment, cancer includes eye cancer, including but not limited to retinoblastoma and uveal melanoma.

[0153] In aspects of this embodiment, the cancer includes gastrointestinal cancer, including but not limited to anal cancer, appendix cancer, cholangiocarcinoma, colon cancer, extrahepatic bile duct cancer, gallbladder cancer, gastric (stomach) cancer, gastrointestinal carcinoid tumors, gastrointestinal stromal tumors (GIST), hepatocellular carcinoma, pancreatic islet cell carcinoma, pancreatic cancer, and rectal cancer.

[0154] In aspects of this embodiment, the cancer includes genitourinary or gynecological cancers, including but not limited to bladder cancer, cervical cancer, endometrial cancer, extragonadal germ cell tumor, gestational choriocarcinoma, ovarian cancer, ovarian epithelial cancer (surface epithelial stromal tumor), ovarian germ cell cancer, penile cancer, renal cell carcinoma, prostate cancer, transitional cell carcinoma (renal pelvis-ureter or ureter and renal pelvis), testicular cancer, urethral cancer, uterine sarcoma, vaginal cancer, vulvar cancer, and Wilms' tumor.

[0155] In aspects of this embodiment, the cancer includes head and neck cancer, including but not limited to esophageal cancer, head cancer, hypopharyngeal cancer, neck cancer, nasopharyngeal cancer, oral cavity cancer, oropharyngeal cancer, paranasal sinus and nasal cavity cancer, pharyngeal cancer, and salivary gland cancer.

[0156] In aspects of this embodiment, the cancer includes acute biphenotypic leukemia, acute eosinophilic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, acute myeloid dendritic cell leukemia, AIDS-related lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, B-cell prolymphocytic leukemia, Burkitt's lymphoma, chronic lymphocytic leukemia, chronic myeloid leukemia, cutaneous T-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia, hepatosplenic T-cell lymphoma, Hodgkin's lymphoma, intravascular large B-cell lymphoma, large granular lymphocytic leukemia, lymphoplasmacytic lymphoma , lymphomatoid granulomatosis, mantle cell lymphoma, marginal zone B-cell lymphoma, mast cell leukemia, mediastinal large B-cell lymphoma, multiple myeloma / plasma cell neoplasms, myelodysplastic syndromes, mucosa-associated lymphoid tissue lymphoma, mycosis fungoides lymphoma, nodal marginal zone B-cell lymphoma, non-Hodgkin's lymphoma, precursor B-lymphoblastic leukemia, primary central nervous system lymphoma, primary cutaneous follicular lymphoma, primary cutaneous immunocytoma, primary effusion lymphoma, plasmablastic lymphoma, Sezary syndrome, splenic marginal zone lymphoma, and T-cell prolymphocytic leukemia.

[0157] In aspects of this embodiment, cancer includes skin cancer, including but not limited to basal cell carcinoma, dermatofibrosarcoma protuberans, melanoma, Merkel cell carcinoma, sebaceous carcinoma, skin adnexal tumor, and squamous cell carcinoma.

[0158] In aspects of this embodiment, the cancer includes thoracic or respiratory cancer, including but not limited to bronchial adenoma / carcinoid, laryngeal carcinoma, mesothelioma, non-small cell lung carcinoma, pleuropulmonary blastoma, small cell lung carcinoma, thymoma, and thymic carcinoma.

[0159] In aspects of this embodiment, cancer includes HIV / AIDS-related cancers, including but not limited to AIDS-related cancers and Kaposi's sarcoma.

[0160] In aspects of this embodiment, cancers include epithelioid hemangioendothelioma (EHE), desmoplastic small round cell tumor, and liposarcoma.

[0161] Aspects of the present specification disclose, in part, a disease or disorder that is chronic inflammation. Inflammation involves the activation of the immune system in response to harmful stimuli, such as pathogens, infections, irritants, or cell damage. As a stereotypical response, inflammation is a mechanism of innate immunity compared to adaptive immunity, which is specific to each pathogen. Inflammation can be classified as either acute or chronic. Generally speaking, acute inflammation is mediated by granulocytes, while chronic inflammation is mediated by mononuclear cells, such as monocytes and lymphocytes.

[0162] Acute inflammation is the body's initial defense response to remove harmful stimuli by maintaining tissue integrity and contributing to tissue repair. It is part of the body's natural defense system against injury and disease; without acute inflammation, wounds and infections would never heal and the progressive destruction of tissues would impair the survival of the organism.

[0163] The process of acute inflammation is initiated by cells already present in all tissues, primarily resident macrophages, dendritic cells, histiocytes, Kupffer cells, mast cells, vascular endothelial cells, and vascular smooth muscle cells. Upon initiation of a noxious stimulus, these cells undergo activation and release inflammatory mediators and sensitizing molecules, such as proinflammatory cytokines, proinflammatory prostaglandins, leukotrienes, histamine, serotonin, neutral proteases, bradykinin, and nitric oxide. These inflammatory molecules regulate a complex series of biological events involving the local vasculature, immune system, and cellular and acellular components of the damaged tissue site to propagate and mature the inflammatory response. These events typically cause the induction of an acute inflammatory response characterized by: 1) increasing blood flow into the tissue, thereby causing erythema (redness and heat) and vasodilation that may spread beyond this site (flare reaction), 2) increasing vascular permeability, thereby causing plasma leakage into the tissue, thereby causing edema (swelling), 3) altering the excitability of certain sensory neurons, causing hypersensitivity and pain, 4) stimulating the release of proinflammatory molecules from peripheral nerve endings, such as neuropeptides, e.g., substance P (SP) and calcitonin gene-related peptide (CGRP), prostaglandins, and amino acids, e.g., glutamate, and 5) increasing the migration of leukocytes, primarily granulocytes, from the blood vessels into the tissue. Acute inflammatory responses require a constant stimulus to persist and must be actively terminated when no longer needed. Thus, acute inflammation ceases when the noxious stimulus is removed.

[0164] However, severe or prolonged harmful stimuli result in a chronic inflammatory response that leads to a progressive shift in the types of cells present at the site of tissue damage. Chronic inflammation may be characterized as the simultaneous destruction and healing of tissue from the inflammatory process, ultimately resulting in inducing damage rather than mediating repair. Thus, chronic inflammation is a disease. Because inflammatory responses can occur anywhere in the body, chronic inflammation is implicated in the pathophysiology of a wide range of seemingly unrelated disorders that underlie a large and diverse group of human diseases. For example, chronic inflammation is involved in such diverse diseases as cardiovascular disease, cancer, allergies, obesity, diabetes, digestive system diseases, degenerative diseases, autoimmune disorders, and Alzheimer's disease.

[0165] Chronic inflammation symptoms include, but are not limited to, edema, hyperemia, erythema, bruising, tenderness, stiffness, swelling, fever, chills, stuffy nose, heavy head, respiratory problems, fluid retention, blood clots, loss of appetite, increased heart rate, formation of granulomas, fibrous, pus, non-viscous serous fluid, or ulcers and pain. The actual symptoms associated with chronic inflammation are well known and can be determined by those skilled in the art by considering factors including, but not limited to, the location of inflammation, the cause of inflammation, the severity of inflammation, the tissue or organ affected, and associated disorders.

[0166] Specific patterns of chronic inflammation are seen during certain situations occurring within the body, such as when inflammation occurs at epithelial surfaces or when pyogenic bacteria are involved. For example, granulomatous inflammation is inflammation resulting from the formation of granulomas resulting from a limited but diverse number of diseases, including but not limited to tuberculosis, leprosy, sarcoidosis, and syphilis. Suppurative inflammation is inflammation that produces copious amounts of pus consisting of neutrophils, dead cells, and fluid. Infections with pyogenic bacteria, such as Staphylococcus aureus, are characteristic of this type of inflammation. Serous inflammation is inflammation resulting from copious exudation of non-viscous serous fluid, generally produced by mesothelial cells of the serous membrane but which may be derived from plasma. Skin blisters exemplify this inflammatory pattern. Ulcerative inflammation is inflammation resulting from necrotic loss of tissue from the epithelial surface, exposing the underlying layers and forming ulcers.

[0167] Chronic inflammatory conditions may be associated with a large group of unrelated disorders that underlie a variety of diseases and disorders. The immune system is often involved in chronic inflammatory disorders, as demonstrated in both allergic reactions and some myopathies, and many immune system disorders result in abnormal inflammation. Non-immune diseases that have an etiological origin in chronic inflammatory processes include cancer, atherosclerosis, and ischemic heart disease.Non-limiting examples of disorders that exhibit chronic inflammation as a symptom include acne, acid reflux / heartburn, age-related macular degeneration (AMD), allergies, allergic rhinitis, Alzheimer's disease, amyotrophic lateral sclerosis, anemia, appendicitis, arteritis, arthritis, asthma, atherosclerosis, autoimmune disorders, balanitis, blepharitis, bronchiolitis, bronchitis, bullous pemphigoid, burns, bursitis, cancer, cardiac arrest, carditis, parsley, and rhinitis. Acne disease, cellulitis, cervicitis, cholangitis, cholecystitis, chorioamnionitis, chronic obstructive pulmonary disease (COPD), cirrhosis, colitis, congestive heart failure, conjunctivitis, cyclophosphamide-induced cystitis, cystic fibrosis, cystitis, cold, dacryoadenitis, dementia, dermatitis, dermatomyositis, diabetes, diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic ulcer, digestive system disease, eczema, emphysema, encephalitis, endocarditis , endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibromyalgia, fibrosis, connective tissue inflammation, gastritis, gastroenteritis, gingivitis, glomerulonephritis, glossitis, heart disease, heart valve dysfunction, hepatitis, hidradenitis suppurativa, Huntington's disease, hyperlipidemic pancreatitis, hypertension, ileitis, infection, inflammatory bowel disease, inflammatory cardiac hypertrophy, insulin resistance, interstitial cystitis, interstitial nephritis, iritis, ischemia, ischemic heart disease, keratitis, Keratoconjunctivitis, laryngitis, lupus nephritis, mastitis, mastoiditis, meningitis, metabolic syndrome (syndrome X), migraine, multiple sclerosis, myelitis, myocarditis, myositis, nephritis, nonalcoholic steatohepatitis, obesity, omphalitis, oophoritis, orchitis, osteochondritis, osteopenia, osteomyelitis, osteoporosis, osteitis, otitis, pancreatitis, Parkinson's disease, parotitis, pelvic inflammatory disease, pemphigus vulgaris vularis), pericarditis, peripheral neuropathy, peritonitis, pharyngitis, phlebitis, pleuritis, pneumonitis, polycystic nephritis, proctitis, prostatitis, psoriasis, pulpitis, pyelonephritis, portal phlebitis, renal failure, reperfusion injury, retinitis, rheumatic fever, rhinitis, salpingitis, sarcoidosis, sialadenitis, sinusitis, spastic colon, stenosis, stomatitis, stroke, surgical complications, synovitis, tendinitis, tendinosis, tenosynovitis, thrombophlebitis, tonsillitis, trauma, traumatic brain injury, transplant rejection, bladder trigonitis, tuberculosis, tumor, urethritis, ursitis, uveitis, vaginitis, vasculitis, and vulvitis.See also, Eric R. First, Application of Botulinum Toxin to the Management of Neurogenic Inflammatory Disorders, U.S. Patent No. 6,063,768, which is incorporated by reference in its entirety.

[0168] In one embodiment, chronic inflammation includes tissue inflammation.Tissue inflammation is chronic inflammation that is limited to a specific tissue or organ.In this embodiment, tissue inflammation includes, for example, skin inflammation, muscle inflammation, tendon inflammation, ligament inflammation, bone inflammation, cartilage inflammation, lung inflammation, heart inflammation, liver inflammation, pancreas inflammation, kidney inflammation, bladder inflammation, stomach inflammation, intestine inflammation, nerve inflammation, and brain inflammation.

[0169] In another embodiment, chronic inflammation includes systemic inflammation. The process involved is the same as tissue inflammation, but systemic inflammation is not limited to a specific tissue, but actually overwhelms the body, including endothelium and other organ systems. When caused by infectious disease, the term sepsis is applied, and the term bacteremia is particularly applied to bacterial sepsis and viremia, especially viral sepsis. Vasodilation and organ dysfunction are serious problems associated with a wide range of infectious diseases that can lead to septic shock and death.

[0170] In another embodiment, chronic inflammation includes arthritis.Arthritis includes a group of conditions involving damage to the joints of the body due to inflammation of the synovial membrane, including but not limited to osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthropathy such as ankylosing spondylitis, reactive arthritis (Reiter's syndrome), psoriatic arthritis, enteropathic arthritis associated with inflammatory bowel disease, Whipple's disease and Behcet's disease, septic arthritis, gout (also known as gouty arthritis, crystalline synovitis, metabolic arthritis), pseudogout (calcium pyrophosphate deposition disease), and Still's disease.Arthritis can affect a single joint (monoarthritis), two to four joints (oligoarthritis), or five or more joints (polyarthritis), and can be either an autoimmune disease or a non-autoimmune disease.

[0171] In another embodiment, chronic inflammation comprises autoimmune disorders. Autoimmune diseases can be broadly divided into systemic and organ-specific autoimmune disorders according to the main clinicopathological features of each disease. Systemic autoimmune diseases include, but are not limited to, systemic lupus erythematosus (SLE), Sjogren's syndrome, scleroderma, rheumatoid arthritis, and polymyositis. Localized autoimmune diseases can be endocrinological (such as type 1 diabetes, Hashimoto's thyroiditis, Addison's disease), dermatological (pemphigus vulgaris), hematological (autoimmune hemolytic anemia), neurological (multiple sclerosis), or involve a well-defined mass in virtually any body tissue. Types of autoimmune disorders include acute disseminated encephalomyelitis (ADEM), Addison's disease, allergies or hypersensitivity disorders, amyotrophic lateral sclerosis, antiphospholipid syndrome (APS), arthritis, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease, autoimmune pancreatitis, bullous pemphigoid, celiac disease, Chagas disease, chronic obstructive pulmonary disease (COPD), type 1 diabetes mellitus (IDDM), endometriosis, fibromyalgia, Goodpasture's syndrome, Graves' disease, Guillain-Barré syndrome (GBS), Hashimoto's thyroiditis, hidradenitis suppurativa, idiopathic thrombocytopenic purpura, These include, but are not limited to, inflammatory bowel disease, interstitial cystitis, lupus (including discoid lupus erythematosus, drug-induced lupus nephritis, neonatal lupus, subacute cutaneous lupus erythematosus, and systemic lupus erythematosus), morphea, multiple sclerosis (MS), myasthenia gravis, myopathy, narcolepsy, neuromyotonia, pemphigus vulgaris, pernicious anemia, primary biliary cirrhosis, relapsing disseminated encephalomyelitis (multiphasic disseminated encephalomyelitis), rheumatic fever, schizophrenia, scleroderma, Sjogren's syndrome, tenosynovitis, vasculitis, and vitiligo. See Pamela D. Van Schaack & Kenneth L. Tong, Treatment of Autoimmune Disorder with a Neurotoxin, U.S. Patent Application Publication No. 2006 / 138059, incorporated herein by reference in its entirety.

[0172] In another embodiment, the chronic inflammation includes myopathy. Myopathy occurs when the immune system inappropriately attacks muscle components, leading to muscle inflammation. Myopathy includes inflammatory myopathy and autoimmune myopathy. Myopathy includes, but is not limited to, dermatomyositis, inclusion body myositis, and polymyositis.

[0173] In another embodiment, chronic inflammation comprises vasculitis.Vasculitis is a group of disorders characterized by inflammation of blood vessel walls, including lymphatic vessels and blood vessels such as veins (phlebitis), arteries (arteritis) and capillaries, due to leukocyte migration and resulting damage.Inflammation may affect blood vessels of any size anywhere in the body. It may affect either arteries and / or veins.Inflammation may be localized, meaning that it affects a single location in blood vessels, or it may be widespread, with areas of inflammation scattered throughout a particular organ or tissue, or even affecting two or more organ systems in the body. Vasculitis includes, but is not limited to, Buerger's disease (thromboangiitis obliterans), cerebral vasculitis (central nervous system vasculitis), Churg-Strauss arteritis, cryoglobulinemia, essential cryoglobulinemic vasculitis, giant cell (temporal) arteritis, golfer's vasculitis, Henoch-Schönlein purpura, hypersensitivity vasculitis (allergic vasculitis), Kawasaki disease, microscopic polyarteritis / polyangiitis, polyarteritis nodosa, polymyalgia rheumatica (PMR), rheumatic vasculitis, Takayasu's arteritis, Wegener's granulomatosis, and vasculitis secondary to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), relapsing polychondritis, connective tissue disorders such as Behçet's disease, or other connective tissue disorders, and vasculitis secondary to viral infections.

[0174] In another embodiment, the chronic inflammation comprises skin disorders.Skin disorders include, but are not limited to, acne, including acne vulgaris; bullous pemphigoid; dermatitis, including atopic dermatitis and chronic photosensitive dermatitis; eczema, such as atopic eczema; contact eczema; dry eczema; seborrheic dermatitis; dyshidrosis; nummular eczema; venous eczema; dermatitis herpetiformis; neurodermatitis; and autosensitization dermatitis; as well as stasis dermatitis, hidradenitis suppurativa, lichen planus, plaqure psoriasis, nail psoriasis, guttate psoriasis, scalp psoriasis, inverse psoriasis, pustular psoriasis, erythrodermis psoriasis, and psoriatic arthritis; rosacea; and scleroderma, including morphea.

[0175] In another embodiment, the chronic inflammation comprises a gastrointestinal disorder, including, but not limited to, irritable bowel disease, inflammatory bowel disease, including Crohn's disease, and ulcerative colitis, such as ulcerative proctitis, left-sided colitis, pancolitis, and fulminant colitis.

[0176] In another embodiment, chronic inflammation includes cardiovascular disease. When LDL cholesterol is embedded in the arterial wall, it can cause an immune response. Chronic inflammation can eventually damage arteries, which can cause them to rupture. Cardiovascular disease is any of several specific diseases that affect the heart itself and / or the vascular system, particularly the veins and arteries that enter and leave the heart. There are more than 60 types of cardiovascular disorders, including but not limited to hypertension, endocarditis, myocarditis, heart valve dysfunction, congestive heart failure, myocardial infarction, diabetic heart condition, vascular inflammation such as arteritis, phlebitis, vasculitis; arteriosclerosis and stenosis, arterial occlusive disease, inflammatory cardiac hypertrophy, peripheral arterial disease; aneurysm; embolism; dissection; pseudoaneurysm; vascular malformation; vascular nevi; thrombosis; thrombphlebitis; varicose veins; stroke. Symptoms of cardiovascular disorders that affect the heart include, but are not limited to, chest pain or discomfort (angina), pain in one or both arms, left shoulder, neck, jaw, or back, shortness of breath, dizziness, fast heartbeat, nausea, abnormal heartbeat, fatigue.Symptoms of cardiovascular disorders that affect the brain include, but are not limited to, sudden numbness or weakness of the face, arms, or legs, especially on one side of the body, sudden confusion or difficulty speaking or understanding speech, sudden difficulty seeing in one or both eyes, sudden dizziness, difficulty walking, or loss of balance or coordination, sudden severe headache of unknown cause.Symptoms of cardiovascular disorders that affect the legs, pelvis, and / or arms include, but are not limited to, claudication (which is muscle pain, soreness, or cramps), and cold or numb feet or toes, especially at night.

[0177] In another embodiment, the chronic inflammation comprises cancer. Inflammation regulates the microenvironment surrounding the tumor and contributes to proliferation, survival, and migration. For example, fibrinous inflammation results from a large increase in vascular permeability, which allows fibrin to pass through blood vessels. In the presence of appropriate procoagulant stimuli, such as cancer cells, fibrous exudates are deposited. This is generally found in serous cavities, and the transformation of fibrous exudates into scars can occur between the serosa, limiting the function of the serosa. In another example, the cancer is an inflammatory cancer, such as NF-κB-driven inflammatory cancer.

[0178] In another embodiment, chronic inflammation comprises pharmacologically induced inflammation.Certain drugs or exogenous chemical compounds are known to affect inflammation.For example, vitamin A deficiency causes an increase in inflammatory response.Certain illegal drugs, such as cocaine and ecstasy, may exert some of their harmful effects by activating transcription factors (e.g. NF-κB) closely involved in inflammation.

[0179] In another embodiment, chronic inflammation includes infectious diseases. Infectious organisms can escape the confines of the immediate tissue via the circulatory or lymphatic system, where they can spread to other parts of the body. If the organism is not contained by the action of acute inflammation, it may access the lymphatic system via nearby lymphatic vessels. Infection of lymphatic vessels is known as lymphangitis, and infection of lymph nodes is known as lymphadenitis. Pathogens may access the bloodstream via lymphatic drainage to the circulatory system. Infectious diseases include, but are not limited to, bacterial cystitis, bacterial encephalitis, pandemic influenza, viral encephalitis, and viral hepatitis (A, B, and C).

[0180] In another embodiment, the chronic inflammation comprises tissue or organ damage, including but not limited to burns, lacerations, wounds, punctures, or trauma.

[0181] In another embodiment, chronic inflammation includes transplant rejection. Transplant rejection occurs when a transplanted organ or tissue is not accepted by the transplant recipient's body because the recipient's immune system attacks the transplanted organ or tissue. Transplant rejection, which is an adaptive immune response, is mediated through both T cell-mediated and humoral immune (antibody) mechanisms. Transplant rejection can be classified as hyperacute rejection, acute rejection, or chronic rejection. Chronic rejection of transplanted organs or tissues is when the rejection is due to poorly understood chronic inflammatory and immune responses to the transplanted tissue. The term "transplant rejection" also includes graft-versus-host disease (GVHD). GVHD is a common complication of allogeneic bone marrow transplantation, where functional immune cells in the transplanted bone marrow recognize the recipient as "foreign" and launch an immunological attack. It can also occur in blood transfusions under certain circumstances. GVHD is divided into acute and chronic forms. Acute and chronic GVHD involve different immune cell subsets, different cytokine profiles, somewhat different host targets, and appear to respond differently to treatment.

[0182] In another embodiment, chronic inflammation includes Th1-mediated inflammatory diseases. In a well-functioning immune system, immune response should result in a balanced pro-inflammatory Th1 response and anti-inflammatory Th2 response suitable for dealing with immune load. Generally speaking, once a pro-inflammatory Th1 response is initiated, the body relies on the anti-inflammatory response caused by the Th2 response to counteract this Th1 response. This counter-response includes the release of Th2-type cytokines, such as IL-4, IL-5, and IL-13, which are associated with the promotion of IgE and eosinophil responses in atopy, and IL-10, which also has an anti-inflammatory response. Th1-mediated inflammatory diseases involve excessive pro-inflammatory responses produced by Th1 cells, which cause chronic inflammation. Th1-mediated diseases may be viral, bacterial, or chemically (e.g., environmental) induced. For example, viruses that cause Th1-mediated diseases may cause chronic or acute infections that may cause respiratory disorders or influenza.

[0183] Neuroinflammation is an inflammatory response of nervous tissue that can be both acute and chronic. Acute neuroinflammatory responses are a well-established defense against harmful conditions such as infections, toxins, and neuronal injury. With respect to the peripheral nervous system (PNS), neuroinflammatory responses are handled in a similar manner to inflammatory responses. The central nervous system (CNS) is considered an immunologically privileged site because the blood-brain barrier (BBB) ​​typically prevents peripheral immune cells from entering the CNS. Instead, in response to inflammatory triggers, resident glial cells called microglia are activated to destroy infectious agents before they can damage nervous tissue, and thus are the primary form of active immune defense in the CNS. However, when the balance between anti-inflammatory and pro-inflammatory signaling is disrupted, microglia become chronically activated, leading to the overproduction of pro-inflammatory factors (i.e., cytokines) and the progression of neurodegenerative changes (e.g., neuronal atrophy and loss of function). Activation of chronic neuroinflammation further induces the infiltration of immune cells from the periphery across the BBB, promoting neuroinflammatory and neurodegenerative processes. Much research has focused on the central role of neuroinflammation in the pathogenesis of many conditions associated with the CNS, including traumatic brain injury, stroke, Alzheimer's disease, postoperative cognitive decline / perioperative neurocognitive impairment, and now even long-term cognitive side effects from SARS-CoV-2. However, attempts to treat neuroinflammation have met with limited success, primarily because NSAIDs are typically formulated for minimal blood-brain barrier penetration. Thus, compounds, compositions, uses, and methods that can successfully deliver anti-inflammatory agents to the brain would be highly desirable for the treatment of neuroinflammation.

[0184] In another embodiment, chronic inflammation includes chronic neurogenic inflammation. Chronic neurogenic inflammation refers to an inflammatory response that is initiated and / or maintained through the release of inflammatory molecules such as SP or CGRP from peripheral sensory nerve endings (i.e., efferent function, as opposed to the normal afferent signaling to the spinal cord in these nerves). Chronic neurogenic inflammation includes both primary and secondary neurogenic inflammation. As used herein, the term "primary" neurogenic inflammation refers to tissue inflammation (inflammatory symptoms) that is initiated by or results from the release of substances from primary sensory nerve endings (such as C and Aδ fibers). As used herein, the term "secondary" neurogenic inflammation" refers to tissue inflammation that is initiated by non-neuronal sources of inflammatory mediators such as peptides or cytokines (e.g., extravasation from vascular beds or tissue interstitium, such as mast cells or immune cells), which stimulate sensory nerve endings and cause the release of inflammatory mediators from nerves. The net effect of both forms of chronic neurogenic inflammation (primary and secondary) is to have an inflammatory state maintained by sensitization of peripheral sensory nerve fibers. The resulting physiological consequences of chronic neurogenic inflammation depend on the tissue in question and can result in, for example, skin pain (allodynia, hyperalgesia), joint pain and / or arthritis, visceral pain and dysfunction, pulmonary dysfunction (asthma, COPD), and bladder dysfunction (pain, overactive bladder).

[0185] Neuroinflammation includes both acute and chronic neuroinflammation. Acute neuroinflammation usually occurs immediately after injury to the central nervous system and is characterized by rapid activation of microglia, release of inflammatory molecules, activation of endothelial cells, platelet deposition, and tissue edema. Chronic neuroinflammation is the persistent activation of glial cells and recruitment of other immune cells to the brain. However, over time, chronic inflammation leads to the degradation of tissues as well as the BBB and the generated reactive oxygen species, and the inflammatory signals released by microglia recruit peripheral immune cells to help initiate a neuroimmune response.

[0186] Chronic inflammation is typically associated with neurodegenerative diseases. Neurodegenerative diseases are caused by the progressive loss of neuronal structure or function in a process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegeneration can be found in the brain at many different levels of neural circuitry, ranging from molecular to systemic. These diseases are considered incurable, as there is no known way to reverse the progressive degeneration of neurons. 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, aneurysms, anxiety, aphasia, Asperger's syndrome, ataxia, attention deficit hyperactivity disorder, bipolar disorder, brain cancer, cancer-related or chemotherapy-related cognitive impairment, cerebral ischemia, cerebral palsy, chronic fatigue syndrome, CNS neuropathy, Creutzfeldt-Jakob disease, dementia, depression, encephalitis, epilepsy, fibromyalgia, functional neuropathy, Guillain-Barré syndrome, headache, idiopathic intracranial hypertension, migraine, multiple sclerosis, Parkinson's disease, pediatric neuroinflammatory disorders, perioperative neurocognitive impairment, postoperative cognitive decline, post-traumatic stress disorder, SARS-CoV-2 infection, schizophrenia, stroke, substance abuse-related neuroinflammation, traumatic brain injury, and Tourette's syndrome.

[0187] Aspects of the present specification disclose, in part, a disease or disorder that is idiopathic pulmonary fibrosis.

[0188] Aspects of the present specification disclose, in part, a disease or disorder that is a renal disease or disorder.

[0189] The composition or compound is administered to an individual.The individual is typically a human.Typically, any individual who is a candidate for conventional chronic inflammation and / or neuroinflammation treatment is a candidate for the disease or disorder treatment disclosed herein.Preoperative evaluation typically includes a thorough informed consent that discloses all the associated risks and benefits of the procedure, as well as a routine medical history and physical examination, including biomarker evaluation.

[0190] The pharmaceutical compositions disclosed herein may comprise a therapeutically effective amount of a therapeutic compound. As used herein, the term "effective amount" is synonymous with "therapeutically effective amount", "effective dose", or "therapeutically effective dose" and, when used in relation to the treatment of a disease or disorder, refers to the minimum dose of a therapeutic compound disclosed herein required to achieve the desired therapeutic effect, including a dose sufficient to alleviate symptoms associated with the disease or disorder. The effectiveness of a therapeutic compound disclosed herein in treating a disease or disorder may be determined by observing an individual's improvement based on one or more clinical symptoms, and / or physiological indicators associated with the condition. Improvement of a disease or disorder may also be indicated by a reduced need for concomitant therapy.

[0191] The appropriate effective amount of the therapeutic compound disclosed herein to be administered to an individual for a particular chronic inflammation and / or neuroinflammation can be determined by one of skill in the art by considering factors including, but not limited to, the type of chronic inflammation and / or neuroinflammation, the location of chronic inflammation and / or neuroinflammation, the cause of chronic inflammation and / or neuroinflammation, the severity of chronic inflammation and / or neuroinflammation, the degree of desired relief, the duration of desired relief, the particular therapeutic compound used, the pharmacokinetic properties of the particular therapeutic compound used, including release, absorption, distribution, metabolism, and excretion, the mechanism of action, the dose-response relationship, the desired activity, undesirable side effects, the pharmacodynamic properties of the particular therapeutic compound used, including therapeutic window and duration of action, the nature of other compounds to be included in the composition, the particular formulation, the particular route of administration, the particular characteristics of the patient, such as age, weight, general health, medical history and risk factors, or any combination thereof. It is known to those of skill in the art that the effective amount of the therapeutic compound disclosed herein can be extrapolated from in vitro assays and in vivo administration tests using animal models before administration to humans. Furthermore, considering the different efficiencies of various administration routes, variations in the required effective amount should be expected. For example, oral administration of the therapeutic compounds disclosed herein would generally be expected to require higher dosage levels than intravenous administration. Similarly, systemic administration of the therapeutic compounds disclosed herein would generally be expected to require higher dosage levels than local administration. Variations in these dosage levels can be adjusted using standard empirical routines of optimization well known to those skilled in the art. Those skilled in the art will also recognize that the condition of an individual can be monitored throughout the course of the methods or uses disclosed herein, and the effective amount of the therapeutic compounds disclosed herein administered can be adjusted accordingly. Thus, the exact therapeutically effective dosage level and pattern is preferably determined by the responsible health care professional, taking into account the factors identified above.

[0192] In some embodiments, a therapeutically effective amount of a therapeutic compound disclosed herein reduces symptoms associated with a disease or disorder, e.g., by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100%. In other aspects of this embodiment, a therapeutically effective amount of a therapeutic compound disclosed herein reduces symptoms associated with a disease or disorder, e.g., by up to 10%, up to 15%, up to 20%, up to 25%, up to 30%, up to 35%, up to 40%, up to 45%, up to 50%, up to 55%, up to 60%, up to 65%, up to 70%, up to 75%, up to 80%, up to 85%, up to 90%, up to 95%, or up to 100%. In still other aspects of this embodiment, a therapeutically effective amount of a therapeutic compound disclosed herein reduces symptoms associated with a disease or disorder by, for example, about 10% to about 100%, about 10% to about 90%, about 10% to about 80%, about 10% to about 70%, about 10% to about 60%, about 10% to about 50%, about 10% to about 40%, about 20% to about 100%, about 20% to about 90%, about 20% to about 80%, about 20% to about 20%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 30% to about 100%, about 30% to about 90%, about 30% to about 80%, about 30% to about 70%, about 30% to about 60%, or about 30% to about 50%.

[0193] In some embodiments, the therapeutically effective amount of the therapeutic compounds disclosed herein generally ranges from about 0.01 mg / kg to about 10 mg / kg. In aspects of these embodiments, the effective amount of the therapeutic compounds disclosed herein may be, for example, at least 0.01 mg / kg, at least 0.05 mg / kg, at least 0.1 mg / kg, at least 0.5 mg / kg, at least 1.0 mg / kg, at least 2.0 mg / kg, at least 3.0 mg / kg, at least 4.0 mg / kg, at least 5.0 mg / kg, at least 6.0 mg / kg, at least 7.0 mg / kg, at least 8.0 mg / kg, at least 9.0 mg / kg, or at least 10 mg / kg. In other aspects of these embodiments, an effective amount of a therapeutic compound disclosed herein may be, for example, up to 0.01 mg / kg, up to 0.05 mg / kg, up to 0.1 mg / kg, up to 0.5 mg / kg, up to 1.0 mg / kg, up to 2.0 mg / kg, up to 3.0 mg / kg, up to 4.0 mg / kg, up to 5.0 mg / kg, up to 6.0 mg / kg, up to 7.0 mg / kg, up to 8.0 mg / kg, up to 9.0 mg / kg, or up to 10 mg / kg.In still other aspects of these embodiments, an effective amount of a therapeutic compound disclosed herein may be, for example, from about 0.01 mg / kg to about 0.05 mg / kg, from about 0.01 mg / kg to about 0.1 mg / kg, from about 0.01 mg / kg to about 0.5 mg / kg, from about 0.01 mg / kg to about 1.0 mg / kg, from about 0.01 mg / kg to about 2.0 mg / kg, from about 0.01 mg / kg to about 3.0 mg / kg, from about 0.01 mg / kg to about 4.0 mg / kg, from about 0.01 mg / kg to about 5.0 mg / kg, from about 0.01 mg / kg to about 6.0 mg / kg, 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 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.

[0194] In some embodiments, a therapeutically effective amount of a therapeutic compound disclosed herein generally ranges from about 0.01 mg / kg / day to about 10 mg / kg / day. In aspects of these embodiments, an effective amount of a therapeutic compound disclosed herein may be, for example, at least 0.01 mg / kg / day, at least 0.05 mg / kg / day, at least 0.1 mg / kg / day, at least 0.5 mg / kg / day, at least 1.0 mg / kg / day, at least 2.0 mg / kg / day, at least 3.0 mg / kg / day, at least 4.0 mg / kg / day, at least 5.0 mg / kg / day, at least 6.0 mg / kg / day, at least 7.0 mg / kg / day, at least 8.0 mg / kg / day, at least 9.0 mg / kg / day, or at least 10 mg / kg / day. In other aspects of these embodiments, an effective amount of a therapeutic compound disclosed herein may be, for example, up to 0.01 mg / kg / day, up to 0.05 mg / kg / day, up to 0.1 mg / kg / day, up to 0.5 mg / kg / day, up to 1.0 mg / kg / day, up to 2.0 mg / kg / day, up to 3.0 mg / kg / day, up to 4.0 mg / kg / day, up to 5.0 mg / kg / day, up to 6.0 mg / kg / day, up to 7.0 mg / kg / day, up to 8.0 mg / kg / day, up to 9.0 mg / kg / day, or up to 10 mg / kg / day. In still other aspects of these embodiments, an effective amount of a therapeutic compound disclosed herein can be, for example, from about 0.01 mg / kg / day to about 0.05 mg / kg / day, from about 0.01 mg / kg / day to about 0.1 mg / kg / day, from about 0.01 mg / kg / day to about 0.5 mg / kg / day, from about 0.01 mg / kg / day to about 1.0 mg / kg / day, from about 0.01 mg / kg / day to about 2.0 mg / kg / day, from about 0.01 mg / kg / day to about 3.0 mg / kg / day, from about 0.01 mg / kg / day to about 4. .0mg / kg / day, about 0.01mg / kg / day to about 5.0mg / kg / day, about 0.01mg / kg / day to about 6.0mg / kg / day, about 0.01mg / kg / day to about 7.0mg / kg / day, about 0.01mg / kg / day to about 8.0mg / kg / day, about 0.01mg / kg / day to about 9.0mg / kg / day, about 0.01mg / kg / day to about 10mg / kg / day, about 0.1mg / kg / day to about 0.5mg / kg / day, about 0.1mg / kg / day to about 1.0mg / kg / day, about 0.1 mg / kg / day to about 2.0 mg / kg / day, about 0.1 mg / kg / day to about 3.0 mg / kg / day, about 0.1 mg / kg / day to about 4.0 mg / kg / day, about 0.1 mg / kg / day to about 5.0 mg / kg / day, about 0.1 mg / kg / day to about 6.0 mg / kg / day, about 0.1 mg / kg / day to about 7.0 mg / kg / day, about 0.1 mg / kg / day to about 8.0 mg / kg / day, about 0.1 mg / kg / day to about 9.0 mg / kg / day, about 0.1 mg / kg / day to about 10 mg / kg / day, about 0.5 mg / kg / day to about 1.0 mg / kg / day, about 0.5 mg / kg / day to about 2.0 mg / kg / day, about 0.5 mg / kg / day to about 3.0 mg / kg / day, about 0.5 mg / kg / day to about 4.0 mg / kg / day, about 0.5 mg / kg / day to about 5.0 mg / kg / day, about 0.5 mg / kg / day to about 6.0 mg / kg / day, 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 ... 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 ... The dose may range from about 1.0 mg / kg / day to about 4.0 mg / kg / day, from about 1.0 mg / kg / day to about 5.0 mg / kg / day, from about 1.0 mg / kg / day to about 6.0 mg / kg / day, from about 1.0 mg / kg / day to about 7.0 mg / kg / day, from about 1.0 mg / kg / day to about 8.0 mg / kg / day, from about 1.0 mg / kg / day to about 9.0 mg / kg / day, or from about 1.0 mg / kg / day to about 10 mg / kg / day.

[0195] Administration may be single or cumulative (continuous administration), and can be readily determined by one of skill in the art. For example, treatment of a disease or disorder may include a single administration of an effective dose of the pharmaceutical composition disclosed herein. Alternatively, treatment of a disease or disorder may include multiple administrations of an effective dose of the pharmaceutical composition administered over a range 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 timing of administration may vary from individual to individual, depending on factors such as the severity of the individual's symptoms. For example, an effective dose of the pharmaceutical composition disclosed herein may be administered to an individual once a day, for an indefinite period of time, or until the individual no longer requires treatment. One of skill in the art will recognize that an individual's condition can be monitored throughout the course of treatment, and the effective amount of the pharmaceutical composition disclosed herein administered can be adjusted accordingly.

[0196] In one embodiment, a pharmaceutical composition comprising a therapeutic compound disclosed herein, upon administration to an individual, results in a biodistribution of the therapeutic compound that differs from the biodistribution of the therapeutic compound contained in the same pharmaceutical composition, except that it does not contain one or more digestive enhancers disclosed herein.

[0197] In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, about 25% to about 35% (by weight) of one or more hard fats, about 30% to about 55% (by weight) of one or more liquid fats, and about 15% to about 35% (by weight) of one or more free C. 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, about 25% to about 35% (by weight) of one or more hard fats, about 30% to about 55% (by weight) of one or more liquid fats, about 15% to about 35% (by weight) of one or more free C 14-24 fatty acids, and about 0.5% to about 5% (by weight) of one or more free C 14-24In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, about 25% to about 35% (by weight) of one or more hard fats, about 30% to about 55% (by weight) of one or more liquid fats, about 2% to about 6% (by weight) of one or more bile acids, about 15% to about 35% (by weight) of one or more free C 14-24 fatty acids, and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 25% to about 35% (by weight) of one or more hard fats, from about 30% to about 55% (by weight) of one or more liquid fats, and from about 15% to about 35% (by weight) of one or more free C. 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 25% to about 35% (by weight) of one or more hard fats, from about 30% to about 55% (by weight) of one or more liquid fats, from about 15% to about 35% (by weight) of one or more free C 14-24 fatty acids, and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, about 25% to about 35% (by weight) of one or more hard fats, about 30% to about 55% (by weight) of one or more liquid fats, about 2% to about 6% (by weight) of one or more bile acids, about 15% to about 35% (by weight) of one or more free C. 14-24 fatty acids, and about 0.5% to about 5% (by weight) of one or more free C 14-24In some embodiments, the protein kinase inhibitor in the above embodiments comprises a serine / threonine kinase inhibitor, a tyrosine kinase inhibitor, or both. In some embodiments, the serine / threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, a ROCK2 kinase inhibitor, or both. In some embodiments, the one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, the one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of fatty acids, preferably oleic acid, stearic acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 The fatty acid surfactant preferably comprises an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the alkali metal or alkaline earth metal oleate in the above embodiment is sodium oleate, the alkali metal or alkaline earth metal stearate in the above embodiment is sodium stearate, and the alkali metal or alkaline earth metal linoleate in the above embodiment is sodium linoleate.

[0198] In some embodiments, the pharmaceutical composition comprises from about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, from about 25% to about 35% (by weight) of one or more hard fats comprising glycerolipids, from about 30% to about 55% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and from about 15% to about 35% (by weight) of one or more free C 14-24In some embodiments, the pharmaceutical composition comprises from about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, from about 25% to about 35% (by weight) of one or more hard fats comprising glycerolipids, from about 30% to about 55% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, from about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, about 25% to about 35% (by weight) of one or more hard fats comprising glycerolipids, about 30% to about 55% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, about 2% to about 6% (by weight) of one or more bile acids, about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 25% to about 35% (by weight) of one or more hard fats comprising glycerolipids, from about 30% to about 55% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and from about 15% to about 35% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 25% to about 35% (by weight) of one or more hard fats comprising glycerolipids, from about 30% to about 55% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, from about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 25% to about 35% (by weight) of one or more hard fats comprising glycerolipids, from about 30% to about 55% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, from about 2% to about 6% (by weight) of one or more bile acids, from about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the protein kinase inhibitor in the above embodiments comprises a serine / threonine kinase inhibitor, a tyrosine kinase inhibitor, or both. In some embodiments, the serine / threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, a ROCK2 kinase inhibitor, or both. In some embodiments, the one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, the one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of fatty acids, preferably oleic acid, stearic acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 The fatty acid surfactant preferably comprises an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the alkali metal or alkaline earth metal oleate in the above embodiment is sodium oleate, the alkali metal or alkaline earth metal stearate in the above embodiment is sodium stearate, and the alkali metal or alkaline earth metal linoleate in the above embodiment is sodium linoleate.

[0199] In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, C 10 -C 24 About 25% to about 35% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Ji- and C 10 -C 24 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, and about 15% to about 35% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, C 10 -C 24 About 25% to about 35% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Ji- and C 10 -C 24 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, C 10 -C 24 About 25% to about 35% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Ji- and C 10 -C 24About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 2% to about 6% (by weight) of one or more bile acids, about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, C 10 -C 24 About 25% to about 35% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Ji- and C 10 -C 24 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, and about 15% to about 35% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, C 10 -C 24 About 25% to about 35% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Ji- and C 10 -C 24 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, C 10 -C 24 About 25% to about 35% (by weight) of one or more hard fats, including triglycerides, C 10 -C24 Mono-, C 10 -C 24 Ji- and C 10 -C 24 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 2% to about 6% (by weight) of one or more bile acids, about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the protein kinase inhibitor in the above embodiments comprises a serine / threonine kinase inhibitor, a tyrosine kinase inhibitor, or both. In some embodiments, the serine / threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, a ROCK2 kinase inhibitor, or both. In some embodiments, the one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, the one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of fatty acids, preferably oleic acid, stearic acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 The fatty acid surfactant preferably comprises an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the alkali metal or alkaline earth metal oleate in the above embodiment is sodium oleate, the alkali metal or alkaline earth metal stearate in the above embodiment is sodium stearate, and the alkali metal or alkaline earth metal linoleate in the above embodiment is sodium linoleate.

[0200] In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, saturating C10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 25% to about 35% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16 -C 18 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 2% to about 6% (by weight) of one or more bile acids, about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 25% to about 35% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16 -C 18 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, and about 15% to about 35% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 25% to about 35% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16-C 18 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, a saturating C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 25% to about 35% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16 -C 18 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, and about 15% to about 35% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, a saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 25% to about 35% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16 -C 18 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, a saturating C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 25% to about 35% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16 -C 18 About 30% to about 55% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 2% to about 6% (by weight) of one or more bile acids, about 15% to about 35% (by weight) of one or more free C 14-24 Fatty acids and about 0.5% to about 5% (by weight) of one or more free C 14-24 In some embodiments, the protein kinase inhibitor in the above embodiments comprises a serine / threonine kinase inhibitor, a tyrosine kinase inhibitor, or both. In some embodiments, the serine / threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, a ROCK2 kinase inhibitor, or both. In some embodiments, the one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, the one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of fatty acids, preferably oleic acid, stearic acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18The fatty acid surfactant preferably comprises an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the alkali metal or alkaline earth metal oleate in the above embodiment is sodium oleate, the alkali metal or alkaline earth metal stearate in the above embodiment is sodium stearate, and the alkali metal or alkaline earth metal linoleate in the above embodiment is sodium linoleate.

[0201] In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, about 35% to about 55% (by weight) of one or more hard fats, about 20% to about 40% (by weight) of one or more liquid fats, and about 20% to about 55% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, about 35% to about 55% (by weight) of one or more hard fats, about 20% to about 40% (by weight) of one or more liquid fats, about 20% to about 55% (by weight) of one or more free C 14-24 fatty acids, and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, about 35% to about 55% (by weight) of one or more hard fats, about 20% to about 40% (by weight) of one or more liquid fats, about 1% to about 6% (by weight) of one or more bile acids, about 20% to about 55% (by weight) of one or more free C 14-24 fatty acids, and about 2% to about 7% (by weight) of one or more free C 14-24In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 35% to about 55% (by weight) of one or more hard fats, from about 20% to about 40% (by weight) of one or more liquid fats, and from about 20% to about 55% (by weight) of one or more free C. 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 35% to about 55% (by weight) of one or more hard fats, from about 20% to about 40% (by weight) of one or more liquid fats, and from about 20% to about 55% (by weight) of one or more free C. 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 35% to about 55% (by weight) of one or more hard fats, from about 20% to about 40% (by weight) of one or more liquid fats, from about 20% to about 55% (by weight) of one or more free C 14-24 fatty acids, and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, about 35% to about 55% (by weight) of one or more hard fats, about 20% to about 40% (by weight) of one or more liquid fats, about 1% to about 6% (by weight) of one or more bile acids, about 20% to about 55% (by weight) of one or more free C. 14-24 fatty acids, and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the protein kinase inhibitor in the above embodiments comprises a serine / threonine kinase inhibitor, a tyrosine kinase inhibitor, or both. In some embodiments, the serine / threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, a ROCK2 kinase inhibitor, or both. In some embodiments, the one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, the one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of fatty acids, preferably oleic acid, stearic acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 The fatty acid surfactant preferably comprises an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the alkali metal or alkaline earth metal oleate in the above embodiment is sodium oleate, the alkali metal or alkaline earth metal stearate in the above embodiment is sodium stearate, and the alkali metal or alkaline earth metal linoleate in the above embodiment is sodium linoleate.

[0202] In some embodiments, the pharmaceutical composition comprises from about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, from about 35% to about 55% (by weight) of one or more hard fats comprising glycerolipids, from about 20% to about 40% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and from about 20% to about 55% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, from about 35% to about 55% (by weight) of one or more hard fats comprising glycerolipids, from about 20% to about 40% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, from about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, about 35% to about 55% (by weight) of one or more hard fats comprising glycerolipids, about 20% to about 40% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, about 1% to about 6% (by weight) of one or more bile acids, about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 35% to about 55% (by weight) of one or more hard fats comprising glycerolipids, from about 20% to about 40% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, and from about 20% to about 55% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 35% to about 55% (by weight) of one or more hard fats comprising glycerolipids, from about 20% to about 40% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, from about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, from about 35% to about 55% (by weight) of one or more hard fats comprising glycerolipids, from about 20% to about 40% (by weight) of one or more liquid fats comprising partially hydrolyzed glycerolipids comprising a mixture of mono-, di-, and triglycerides, from about 1% to about 6% (by weight) of one or more bile acids, from about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24In some embodiments, the protein kinase inhibitor in the above embodiments comprises a serine / threonine kinase inhibitor, a tyrosine kinase inhibitor, or both. In some embodiments, the serine / threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, a ROCK2 kinase inhibitor, or both. In some embodiments, the one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, the one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of fatty acids, preferably oleic acid, stearic acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 The fatty acid surfactant preferably comprises an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the alkali metal or alkaline earth metal oleate in the above embodiment is sodium oleate, the alkali metal or alkaline earth metal stearate in the above embodiment is sodium stearate, and the alkali metal or alkaline earth metal linoleate in the above embodiment is sodium linoleate.

[0203] In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, C 10 -C 24 About 35% to about 55% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Ji- and C 10 -C 24About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, and about 20% to about 55% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, C 10 -C 24 About 35% to about 55% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Ji- and C 10 -C 24 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, C 10 -C 24 About 35% to about 55% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Ji- and C 10 -C 24 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 1% to about 6% (by weight) of one or more bile acids, about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, C 10 -C 24 About 35% to about 55% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24Mono-, C 10 -C 24 Ji- and C 10 -C 24 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, and about 20% to about 55% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, C 10 -C 24 About 35% to about 55% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Ji- and C 10 -C 24 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, C 10 -C 24 About 35% to about 55% (by weight) of one or more hard fats, including triglycerides, C 10 -C 24 Mono-, C 10 -C 24 Ji- and C 10 -C 24 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 1% to about 6% (by weight) of one or more bile acids, about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24In some embodiments, the protein kinase inhibitor in the above embodiments comprises a serine / threonine kinase inhibitor, a tyrosine kinase inhibitor, or both. In some embodiments, the serine / threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, a ROCK2 kinase inhibitor, or both. In some embodiments, the one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, the one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of fatty acids, preferably oleic acid, stearic acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18 The fatty acid surfactant preferably comprises an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. In some embodiments, the alkali metal or alkaline earth metal oleate in the above embodiment is sodium oleate, the alkali metal or alkaline earth metal stearate in the above embodiment is sodium stearate, and the alkali metal or alkaline earth metal linoleate in the above embodiment is sodium linoleate.

[0204] In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, saturating C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 35% to about 55% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16-C 18 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, and about 20% to about 55% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 35% to about 55% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16 -C 18 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises about 0.5% to about 20% (by weight) of one or more protein kinase inhibitors, saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 35% to about 55% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16 -C 18 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 1% to about 6% (by weight) of one or more bile acids, about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, a saturating C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 35% to about 55% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16 -C 18 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, and about 20% to about 55% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, a saturated C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 35% to about 55% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18 Mono-, C 16 -C 18 Ji- and C 16 -C 18 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including mixtures of triglycerides, about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the pharmaceutical composition comprises from about 10 mg / mL to about 150 mg / mL of one or more protein kinase inhibitors, a saturating C 10 -C 18 Triglycerides and / or Saturated C 12 -C 18 About 35% to about 55% (by weight) of one or more hard fats, including a mixture of triglycerides, C 16 -C 18Mono-, C 16 -C 18 Ji- and C 16 -C 18 About 20% to about 40% (by weight) of one or more liquid fats, including partially hydrolyzed triglycerides, including a mixture of triglycerides, about 1% to about 6% (by weight) of one or more bile acids, about 20% to about 55% (by weight) of one or more free C 14-24 Fatty acids and about 2% to about 7% (by weight) of one or more free C 14-24 In some embodiments, the protein kinase inhibitor in the above embodiments comprises a serine / threonine kinase inhibitor, a tyrosine kinase inhibitor, or both. In some embodiments, the serine / threonine kinase inhibitor in the above embodiments comprises a MAPK kinase inhibitor, a ROCK2 kinase inhibitor, or both. In some embodiments, the one or more bile acids in the above embodiments comprise cholic acid. In some embodiments, the one or more free C in the above embodiments comprises 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of fatty acids, preferably oleic acid, stearic acid, linoleic acid, or any combination thereof. 14-24 Fatty acid surfactants contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C in the above embodiments include fatty acid surfactants, preferably alkali metal or alkaline earth metal oleates, alkali metal or alkaline earth metal stearates, alkali metal or alkaline earth metal linoleates, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 In some embodiments, the one or more bile acids in the above embodiments include cholic acid, and the one or more free C 14-24 Fatty acid surfactants contain one or more free C 14-18In some embodiments, one or more of the free C in the above embodiments may be selected from the group consisting of an alkali metal or alkaline earth metal oleate, an alkali metal or alkaline earth metal stearate, an alkali metal or alkaline earth metal linoleate, or any combination thereof. 14-24 Fatty acids contain one or more free C 14-18 The fatty acid, preferably oleic acid, steric acid, linoleic acid, or any combination thereof, and one or more free C 14-24 Fatty acid surfactants contain one...

Claims

1. a) a pharmaceutical composition comprising one or more therapeutic compounds, b) one or more glycerolipids, and c) one or more digestive aids, wherein the one or more therapeutic compounds include a protein kinase inhibitor or a PARP inhibitor.

2. The pharmaceutical composition according to claim 1, wherein the protein kinase inhibitor is a tyrosine protein kinase inhibitor, a serine-threonine protein kinase inhibitor, or a nonspecific protein kinase inhibitor.

3. The one or more therapeutic compounds are present in amounts of approximately 0.05% to approximately 1% by weight, approximately 0.05% to approximately 2.5% by weight, approximately 0.05% to approximately 5% by weight, approximately 0.05% to approximately 7.5% by weight, approximately 0.05% to approximately 10% by weight, approximately 0.05% to approximately 12.5% ​​by weight, approximately 0.05% to approximately 15% by weight, approximately 0.05% to approximately 17.5% by weight, approximately 0.05% to approximately 20% by weight, approximately 0.05% to approximately 22.5% by weight, approximately 0.05% to approximately 25% by weight, approximately 0.05% to approximately 30% by weight, and approximately 0. 05% to about 40% by weight, about 0.05% to about 50% by weight, about 0.1% to about 1% by weight, about 0.1% to about 2.5% by weight, about 0.1% to about 5% by weight, about 0.1% to about 7.5% by weight, about 0.1% to about 10% by weight, about 0.1% by weight wt% to about 12.5 wt%, about 0.1 wt% to about 15 wt%, about 0.1 wt% to about 17.5 wt%, about 0.1 wt% to about 20 wt%, about 0.1 wt% to about 22.5 wt%, about 0.1 wt% to about 25 wt%, about 0.1 wt% to about 30 wt%, 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% by weight %, about 1% to about 17.5%, about 1% to about 20%, about 1% to about 22.5%, about 1% to about 25%, about 1% to about 30%, about 1% to about 40%, about 1% to about 50%, about 5% to about 10% by weight The pharmaceutical composition according to claim 1, in an amount of approximately 5% by weight to approximately 20% by weight, approximately 5% by weight to approximately 30% by weight, approximately 5% by weight to approximately 40% by weight, approximately 5% by weight to approximately 50% by weight, approximately 10% by weight to approximately 20% by weight, approximately 10% by weight to approximately 30% by weight, approximately 10% by weight to approximately 40% by weight, approximately 10% by weight to approximately 50% by weight, approximately 20% by weight to approximately 30% by weight, approximately 20% by weight to approximately 40% by weight, approximately 20% by weight to approximately 50% by weight, approximately 30% by weight to approximately 40% by weight, approximately 30% by weight to approximately 50% by weight, or approximately 40% by weight to approximately 50% by weight.

4. The one or more therapeutic compounds are present in concentrations of approximately 10 mg / mL to approximately 25 mg / mL, approximately 10 mg / mL to approximately 50 mg / mL, approximately 10 mg / mL to approximately 75 mg / mL, approximately 10 mg / mL to approximately 100 mg / mL, approximately 10 mg / mL to approximately 125 mg / mL, approximately 10 mg / mL to approximately 150 mg / mL, approximately 10 mg / mL to approximately 200 mg / mL, approximately 10 mg / mL to approximately 250 mg / mL, approximately 10 mg / mL to approximately 300 mg / mL, approximately 25 mg / mL to approximately 50 mg / mL, and approximately 25 mg / mL 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 m g / 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 30 0 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 300 mg / mL, about 125 mg / mL to about 150 mg The pharmaceutical composition according to claim 1, in an amount of approximately 125 mg / mL to approximately 200 mg / mL, approximately 125 mg / mL to approximately 250 mg / mL, approximately 125 mg / mL to approximately 300 mg / mL, approximately 150 mg / mL to approximately 200 mg / mL, approximately 150 mg / mL to approximately 250 mg / mL, approximately 150 mg / mL to approximately 300 mg / mL, approximately 200 mg / mL to approximately 250 mg / mL, approximately 200 mg / mL to approximately 300 mg / mL, or approximately 250 mg / mL to approximately 300 mg / mL.

5. The one or more glycerolipids are present in amounts of 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, and / or 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, and up to 90% by weight. Or up to 95% by weight, or approximately 40% to 50% by weight, approximately 40% to 55% by weight, approximately 40% to 60% by weight, approximately 40% to 65% by weight, approximately 40% to 70% by weight, approximately 40% to 75% by weight, approximately 40% to 80% by weight, approximately 40% to 85% by weight, approximately 40% to 90% by weight, approximately 40% to 95% by weight, approximately 45% to 55% by weight, approximately 45% to 60% by weight, approximately 45% to 65% by weight, approximately 45% to 70% by weight, approximately 45% to 75% by weight, approximately 45% to 80% by weight, approximately 45% to 8 5% by weight, 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% by weight ~85% by weight, approximately 50% by weight to approximately 90% by weight, approximately 50% to approximately 95% by weight, approximately 55% to approximately 60% by weight, approximately 55% to approximately 65% ​​by weight, approximately 55% to approximately 70% by weight, approximately 55% to approximately 75% by weight, approximately 55% to approximately 80% by weight, approximately 55% to approximately 85% by weight, approximately 55% by weight % to about 90% by weight, 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 6% by weight 5% 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%,A pharmaceutical composition according to any one of claims 1 to 4, in an amount of approximately 70% to approximately 90% by weight, approximately 70% to approximately 95% by weight, approximately 75% to approximately 80% by weight, approximately 75% to approximately 85% by weight, approximately 75% to approximately 90% by weight, approximately 75% to approximately 95% by weight, approximately 80% to approximately 85% by weight, approximately 80% to approximately 90% by weight, approximately 80% to approximately 95% by weight, approximately 85% to approximately 90% by weight, approximately 85% to approximately 95% by weight, or approximately 90% to approximately 95% by weight.

6. The pharmaceutical composition according to claim 5, wherein the one or more glycerolipids comprises one or more hard fats and one or more liquid fats.

7. The pharmaceutical composition according to claim 6, wherein the one or more hard fats comprise one or more triglycerides.

8. The one or more hard fats are 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, and / or 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, or about 10% by weight to about 20% by weight, about 1 0% to about 25% by weight, about 10% to about 30% by weight, about 10% to about 35% by weight, about 10% to about 40% by weight, about 10% to about 45% by weight, about 10% to about 50% by weight, about 10% to about 55% by weight, about 10% to about 60% by weight, about 15% to about 20% by weight, 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% by weight %, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 25% to about 30%, about 25% to about 35% by weight % by weight, 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 These are amounts of 50% by weight, approximately 30% to 55% by weight, approximately 30% to 60% by weight, approximately 35% to 40% by weight, approximately 35% to 45% by weight, approximately 35% to 50% by weight, approximately 35% to 55% by weight, approximately 35% to 60% by weight, approximately 40% to 45% by weight, approximately 40% to 50% by weight, approximately 40% to 55% by weight, approximately 40% to 60% by weight, approximately 45% to 50% by weight, approximately 45% to 55% by weight, approximately 45% to 60% by weight, approximately 50% to 55% by weight, approximately 50% to 60% by weight, and approximately 55% to 60% by weight.The pharmaceutical composition according to claim 6.

9. The pharmaceutical composition according to claim 6, wherein the one or more liquid fats comprise one or more partially hydrolyzed glycerolipids, one or more monoglycerides, or a combination thereof.

10. The pharmaceutical composition according to claim 9, wherein the one or more partially hydrolyzed glycerolipids comprise a mixture of mono-, di-, and triglycerides.

11. The one or more partially hydrolyzed glycerolipids are present in amounts of 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, and / or 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, or about 10% to about 20% by weight. % by weight, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 15% to about 2 0% by weight, 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% by weight, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 25% to about 30%, about 25% by weight about 35% by weight, 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% by weight These amounts are approximately 50% by weight, 30% to 55% by weight, 30% to 60% by weight, 35% to 40% by weight, 35% to 45% by weight, 35% to 50% by weight, 35% to 55% by weight, 35% to 60% by weight, 40% to 45% by weight, 40% to 50% by weight, 40% to 55% by weight, 40% to 60% by weight, 45% to 50% by weight, 45% to 55% by weight, 45% to 60% by weight, 50% to 55% by weight, 50% to 60% by weight, and 55% to 60% by weight.The pharmaceutical composition according to claim 9.

12. The one or more monoglycerides are present in amounts of 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, and / or 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, or about 10% by weight to about 20% by weight, about 10% to about 25%, about 10% to about 30%, about 10% to about 35%, about 10% to about 40%, about 10% to about 45%, about 10% to about 50%, about 10% to about 55%, about 10% to about 60%, about 15% to about 20% by weight %, 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% by weight % by weight, about 20% to about 30%, about 20% to about 35%, about 20% to about 40%, about 20% to about 45%, about 20% to about 50%, about 20% to about 55%, about 20% to about 60%, about 25% to about 30%, about 25% to about 3 5% by weight, 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 These are amounts of 50% by weight, approximately 30% to 55% by weight, approximately 30% to 60% by weight, approximately 35% to 40% by weight, approximately 35% to 45% by weight, approximately 35% to 50% by weight, approximately 35% to 55% by weight, approximately 35% to 60% by weight, approximately 40% to 45% by weight, approximately 40% to 50% by weight, approximately 40% to 55% by weight, approximately 40% to 60% by weight, approximately 45% to 50% by weight, approximately 45% to 55% by weight, approximately 45% to 60% by weight, approximately 50% to 55% by weight, approximately 50% to 60% by weight, and approximately 55% to 60% by weight.The pharmaceutical composition according to claim 9.

13. The pharmaceutical composition according to claim 6, wherein the ratio of one or more hard fats and one or more liquid fats is approximately 5:1 to approximately 4:1, approximately 5:1 to approximately 3:1, approximately 5:1 to approximately 2:1, approximately 5:1 to approximately 1:1, approximately 4:1 to approximately 3:1, approximately 4:1 to approximately 2:1, approximately 4:1 to approximately 1:1, approximately 3:1 to approximately 2:1, approximately 3:1 to approximately 1:1, or approximately 2:1 to approximately 1:

1.

14. The pharmaceutical composition according to claim 6, wherein the one or more hard fats and the one or more liquid fats have a hard fat to liquid fat ratio of approximately 1:5 to approximately 1:4, approximately 1:5 to approximately 1:3, approximately 1:5 to approximately 1:2, approximately 1:5 to approximately 1:1, approximately 1:4 to approximately 1:3, approximately 1:4 to approximately 1:2, approximately 1:4 to approximately 1:1, approximately 1:3 to approximately 1:2, approximately 1:3 to approximately 1:1, or approximately 1:2 to approximately 1:

1.

15. The one or more digestive aids are present in amounts of 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, and at least 75% by weight. %, at least 75% by weight and / or up to 1% by weight, up to 2.5% by weight, up to 5% by weight, up to 7.5% by weight, up to 10% by weight, up to 12.5% ​​by weight, up to 15% by weight, up to 17.5% by weight, up to 20% by weight, up to 22.5% by weight, up to 25% by weight, up to 30% by weight, up to 35% by weight, up to 40% by weight, up to 45% by weight, up to 50% by weight, up to 55% by weight, up to 60% by weight, up to 65% by weight, up to 70% by weight, up to 75% by weight, or up to 80% by weight, or about 1% to about 2.5% by weight, about 1% to about 5% by weight, about 1% to about 10% by weight, about 1 about 1% to about 20%, about 1% to about 25%, about 2.5% to about 5%, about 2.5% to about 10%, about 2.5% to about 15%, about 2.5% to about 20%, about 2.5% to about 25%, about 5% to about 10% by weight, about 5% to about 15%, about 5% to about 20%, 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 1 0% 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% 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 55% by weight, about 20% to about 60% by weight, about 20% to about 65% by weight, about 20% to about 70% by weight, about 25% to about 30% by weight % by weight, 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% by weight, 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% by weight % to about 45 wt%, about 35 wt% to about 50 wt%, about 35 wt% to about 55 wt%, about 35 wt% to about 60 wt%, about 35 wt% to about 65 wt%, about 35 wt% to about 70 wt%, about 40 wt% to about 45 wt%, about 40 wt% to about 50 wt%, about 40 wt% to about 55 wt%, about 4 0% 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% by weight , 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% by weight A pharmaceutical composition according to any one of claims 1 to 4, in an amount of approximately 55% by weight to approximately 60% by weight, approximately 55% by weight to approximately 65% ​​by weight, approximately 55% by weight to approximately 70% by weight, approximately 55% by weight to approximately 75% by weight, approximately 55% by weight to approximately 80% by weight, approximately 60% by weight to approximately 65% ​​by weight, approximately 60% by weight to approximately 70% by weight, approximately 60% by weight to approximately 75% by weight, approximately 60% by weight to approximately 80% by weight, approximately 65% ​​by weight to approximately 70% by weight, approximately 65% ​​by weight to approximately 75% by weight, approximately 65% ​​by weight to approximately 80% by weight, approximately 70% by weight to approximately 75% by weight, or approximately 75% by weight to approximately 80% by weight.

16. The one or more digestive aids include one or more bile acids, one or more phospholipids, and one or more free C. １４－２４ fatty acids, one or more free carbon atoms １４－２４ The pharmaceutical composition according to claim 1, comprising a fatty acid surfactant or any combination thereof.

17. The pharmaceutical composition according to claim 16, wherein the one or more bile acids include cholic acid, chenodeoxycholic acid, dafacuronic acid, deoxycholic acid, glycocholic acid, glycohenodeoxycholic acid, litcholic acid, taurochenodeoxycholic acid, taurocholic acid, any stereoisomers thereof, and any combination thereof.

18. The one or more of the aforementioned bile acids are present in amounts of 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, and at least 9. 5% by weight, or at least 10.0% by weight, and / or up to 0.1% by weight, up to 0.5% by weight, up to 1.0% by weight, up to 1.5% by weight, up to 2.0% by weight, up to 2.5% by weight, up to 3.0% by weight, up to 3.5% by weight, up to 4.0% by weight, up to 4.5% by weight, up to 5.0% by weight, up to 5.5% by weight, up to 6.0% by weight, up to 6.5% by weight, up to 7.0% by weight, up to 7.5% by weight, up to 8.0% by weight, up to 8.5% by weight, up to 9.0% by weight, up to 9.5% by weight, or up to 10.0% by weight, or about 0.1% to about 0.5% by weight, about 0.1% % to about 1.0 wt%, about 0.1 wt% to about 2.0 wt%, about 0.1 wt% to about 3.0 wt%, about 0.1 wt% to about 4.0 wt%, about 0.1 wt% to about 5.0 wt%, about 0.1 wt% to about 6.0 wt%, about 0.1 wt% to about 7.0 wt%, about 0.1 wt% to about 8.0 wt%, 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 weight %, about 0.5 weight % to about 7.0 weight %, about 0.5 weight % to about 8.0 weight %, about 0.5 weight % to about 9.0 weight %, about 0.5 weight % to about 10.0 weight %, about 1.0 weight % to about 2.0 weight %, about 1.0 weight % to about 3.0 weight %, about 1.0 weight % to about 4.0 weight %, about 1.0 weight % % to about 5.0 wt%, about 1.0 wt% to about 6.0 wt%, about 1.0 wt% to about 7.0 wt%, about 1.0 wt% to about 8.0 wt%, about 1.0 wt% to about 9.0 wt%, about 1.0 wt% to about 10.0 wt%, about 2.0 wt% to about 3.0 wt%, about 2.0 wt% to about 4.0 wt%,About 2.0% to about 5.0% by weight, about 2.0% to about 6.0% by weight, about 2.0% to about 7.0% by weight, about 2.0% to about 8.0% by weight, about 2.0% to about 2.0% by weight about 9.0% by weight, about 2.0% by weight to about 10.0% by weight, about 3.0% to about 4.0% by weight, about 3.0% to about 5.0% by weight, about 3.0% to about 6.0% by weight , about 3.0% to about 7.0% by weight, about 3.0% to about 8.0% by weight, about 3.0% to about 9.0% by weight, about 3.0% to about 10.0% by weight, about 4.0% by weight % to about 5.0% by weight, about 4.0% to about 6.0% by weight, about 4.0% to about 7.0% by weight, about 4.0% to about 8.0% by weight, about 4.0% to about 9.0% by weight The pharmaceutical composition according to claim 16, in an amount of approximately 4.0% by weight to approximately 10.0% by weight, approximately 5.0% by weight to approximately 6.0% by weight, approximately 5.0% by weight to approximately 7.0% by weight, approximately 5.0% by weight to approximately 8.0% by weight, approximately 5.0% by weight to approximately 9.0% by weight, approximately 5.0% by weight to approximately 10.0% by weight, approximately 6.0% by weight to approximately 7.0% by weight, approximately 6.0% by weight to approximately 8.0% by weight, approximately 6.0% by weight to approximately 9.0% by weight, approximately 6.0% by weight to approximately 10.0% by weight, approximately 7.0% by weight to approximately 8.0% by weight, approximately 7.0% by weight to approximately 9.0% by weight, approximately 7.0% by weight to approximately 10.0% by weight, approximately 8.0% by weight to approximately 9.0% by weight, or approximately 9.0% by weight to approximately 10.0% by weight.

19. The one or more free carbon atoms １４－２４ Fatty acids in amounts of 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, at least 75% by weight, and / or up to 1% by weight, up to 2.5% by weight, up to 5% by weight, up to 7.5% by weight, Up to 10% by weight, up to 12.5% ​​by weight, up to 15% by weight, up to 17.5% by weight, up to 20% by weight, up to 22.5% by weight, up to 25% by weight, up to 30% by weight, up to 35% by weight, up to 40% by weight, up to 50% by weight, up to 60% by weight, up to 70% by weight, up to 75% by weight, or approximately 1% to approximately 2.5% by weight, approximately 1% to approximately 5% by weight, approximately 1% to approximately 10% by weight, approximately 1% to approximately 15% by weight, approximately 1% to approximately 20% by weight, approximately 1% to approximately 25% by weight, approximately 2.5% to approximately 5% by weight, approximately 2.5% to approximately 10% by weight, approximately 2.5% to approximately 15% by weight, approximately 2.5% % to about 20% by weight, about 2.5% to about 25% by weight, about 2.5% to about 30% by weight, about 5% to about 10% by weight, about 5% to about 15% by weight, about 5% to about 20% by weight, about 5% to about 25% by weight, about 5% to about 30% by weight, about 10% to about 15% by weight, about 10% by weight % to about 20 wt%, about 10 wt% to about 25 wt%, about 10 wt% to about 30 wt%, about 10 wt% to about 40 wt%, about 10 wt% to about 45 wt%, about 10 wt% to about 50 wt%, about 10 wt% to about 60 wt%, about 10 wt% to about 70 wt%, about 15 wt% to about 20 wt%, 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%, about 20% to about 50%, about 20% to about 60%, about 20% to about 70%, about 30% to about 40%, about 30% to about 50%, about 30% to about 60%, about 30% to about 70%,The pharmaceutical composition according to claim 16, in an amount of approximately 30% to approximately 75% by weight, approximately 35% to approximately 40% by weight, approximately 35% to approximately 50% by weight, approximately 35% to approximately 60% by weight, approximately 35% to approximately 70% by weight, approximately 35% to approximately 75% by weight, approximately 40% to approximately 50% by weight, approximately 40% to approximately 60% by weight, approximately 40% to approximately 70% by weight, approximately 40% to approximately 75% by weight, approximately 50% to approximately 60% by weight, approximately 50% to approximately 70% by weight, or approximately 60% to approximately 70% by weight.

20. The one or more free carbon atoms １４－２４ The fatty acid surfactant is present in amounts of 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, and at least 10.0% by weight. %, and / or up to 0.1% by weight, up to 0.5% by weight, up to 1.0% by weight, up to 1.5% by weight, up to 2.0% by weight, up to 2.5% by weight, up to 3.0% by weight, up to 3.5% by weight, up to 4.0% by weight, up to 4.5% by weight, up to 5.0% by weight, up to 5.5% by weight, up to 6.0% by weight, up to 6.5% by weight, up to 7.0% by weight, up to 7.5% by weight, up to 8.0% by weight, up to 8.5% by weight, up to 9.0% by weight, up to 9.5% by weight, up to 10.0% by weight, or approximately 0.1% to approximately 0.5% by weight, approximately 0.1% to approximately 1.0% by weight, approximately 0.1% to approximately 2.0% by weight, 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 wt%, about 0.5 wt% to about 1.0 wt%, about 0.5 wt% to about 2.0 wt%, about 0.5 wt% to about 3.0 wt%, about 0.5 wt% to about 4.0 wt%, about 0.5 wt% to about 5.0 wt%, about 0.5 wt% to about 6.0 wt%, about 0.5 wt% to about 7.0 wt%, about 0.5 wt% to about 8.0% by weight, about 0.5% by weight to about 9.0% by weight, about 0.5% to about 10.0% by weight, about 1.0% to about 2.0% by weight, about 1.0% to about 3.0% by weight, about 1.0% to about 4.0% by weight, about 1.0% to about 5.0% by weight, about 1.0% to about 6.0% by weight, about 1.0% by weight wt% to about 7.0 wt%, about 1.0 wt% to about 8.0 wt%, about 1.0 wt% to about 9.0 wt%, about 1.0 wt% to about 10.0 wt%, about 2.0 wt% to about 3.0 wt%, about 2.0 wt% to about 4.0 wt%, about 2.0 wt% to about 5.0 wt%, about 2.0 wt% to about 6.0 wt%,about 2.0% to about 7.0% by weight, 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% by weight, about 3.0% to about 5.0% by weight, about 3.0% to about 6.0% by weight, about 3.0% to about 7.0% by weight, about 3.0% by weight ~about 8.0% by weight, about 3.0% by weight - about 9.0% by weight, about 3.0% by weight - about 10.0% by weight, about 4.0% by weight - about 5.0% by weight, about 4.0% by weight - about 6 .0 weight%, about 4.0 weight% to about 7.0 weight%, about 4.0 weight% to about 8.0 weight%, about 4.0 weight% to about 9.0 weight%, about 4.0 weight% to about 10.0 weight%. The pharmaceutical composition according to claim 16, in an amount of %, approximately 5.0% by weight to approximately 6.0% by weight, approximately 5.0% by weight to approximately 7.0% by weight, approximately 5.0% by weight to approximately 8.0% by weight, approximately 5.0% by weight to approximately 9.0% by weight, approximately 5.0% by weight to approximately 10.0% by weight, approximately 6.0% by weight to approximately 7.0% by weight, approximately 6.0% by weight to approximately 8.0% by weight, approximately 6.0% by weight to approximately 9.0% by weight, approximately 6.0% by weight to approximately 10.0% by weight, approximately 7.0% by weight to approximately 8.0% by weight, approximately 7.0% by weight to approximately 9.0% by weight, approximately 7.0% by weight to approximately 10.0% by weight, approximately 8.0% by weight to approximately 9.0% by weight, or approximately 9.0% by weight to approximately 10.0% by weight.

21. The pharmaceutical composition according to claim 2, wherein the tyrosine protein kinase inhibitor is a receptor tyrosine kinase inhibitor or a non-receptor tyrosine kinase inhibitor.

22. The pharmaceutical composition according to claim 2, wherein the serine-threonine protein kinase inhibitor is a receptor serine-threonine kinase inhibitor or a non-receptor serine-threonine kinase inhibitor.

23. The pharmaceutical composition according to any one of claims 1 to 4, wherein the pharmaceutical composition is not an emulsion or a self-emulsifying preparation.

24. A pharmaceutical composition for use in the treatment of a disease or disorder, as defined by any one of claims 1 to 4.

25. The pharmaceutical composition according to claim 24, wherein the disease or disorder includes neoplasms, cancer, inflammation, autoimmune disorders, idiopathic pulmonary fibrosis, and kidney disease or kidney impairment.

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