Suppository capsule

Abstract

To provide a suppository, and to provide a method of preparing the suppository.SOLUTION: Provided is a suppository comprising a suppository base. The suppository has a length measured along a horizontal axis, that is greater than a width measured along a vertical axis. The suppository has a proximal end along the horizontal axis adapted for insertion into a body cavity and a distal end along the horizontal axis having at least one indentation. Further the suppository comprises an active agent dispersed in the suppository base.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] Related Applications This application was filed on October 31, 2019, which is incorporated herein by reference in its entirety. This application claims priority to U.S. Provisional Patent Application No. 62 / 928,679, filed on 2004 / 01 / 14.

[0002] The present invention relates to suppository capsules, particularly softgel suppository capsules, their preparation methods, and It relates to how to use it. [Background technology]

[0003] Suppositories are commonly shaped like bullets, tampons, ovals, egg shapes, teardrops, and torpedoes. Regardless of their form, suppositories can be difficult to handle and / or administer. With some shapes, the direction of insertion of the suppository may be unclear. The shape of the drug may make it prone to falling out of the patient's hands, making it difficult to handle and / or administer. These issues are partially addressed by providing instructions on handling and / or administration. However, there are still some limitations regarding the handling and / or administration methods. Producing user-friendly suppositories could benefit the existing suppository market. Summary of the Invention

[0004] The present disclosure may be directed to a suppository comprising a suppository base. The suppository may have a linear dimension measured along a vertical axis. The suppository may have a length measured along the horizontal axis that is greater than the diameter. The suppository may have a proximal end and a distal end. The proximal end of the suppository may be adapted for insertion into a body cavity of a subject. The distal end of the suppository may have at least one depression.

[0005] The suppository may be designed for "easy grip" to facilitate handling and / or administration of the suppository. The present invention may also be a soft gel suppository capsule having at least one cavity. Described recessed suppository shapes include, but are not limited to, recessed bullets and recessed suppositories. Any shape such as a hollow oval, hollow oval, hollow teardrop, or hollow torpedo. The at least one depression may be, but is not limited to, flat, concave, or may be perforated.

[0006] The suppositories described herein may include an active agent. In some embodiments, the suppository comprises a core and The active agent may be present in only the core, only the shell, or both the core and the shell. In certain embodiments, the active agent may be present in its entirety in both the suppository and the shell. In certain embodiments, the active agent may be dispersed in at least a portion of the suppository. (e.g., at least the distal portion of the suppository).

[0007] Certain embodiments of the present disclosure include any of the recessed suppository capsules described herein. The present invention may be directed to a method for preparing a suppository comprising: dissolving a liquid core comprising a suppository base in a shell (e.g., and encapsulating the gelatin shell (e.g., via rotary die stamping). The method comprises: dissolving a solid core comprising a suppository base in a liquid shell composition (e.g., a gelatin shell composition) to obtain a suppository. The method may also include a step of immersing the substrate in a solution of the composition.

[0008] Certain embodiments of the present disclosure are directed to, but are not limited to, pain, migraines, inflammation, fungal infections, cellular Bacterial infections, viral infections, vaginal pain, menopausal symptoms, vulvar and vaginal atrophy, cancer, nausea, vomiting, The present invention may be directed to a method of treating a disease or condition, such as a steroid hormone, a steroid hormone, or a combination thereof. Any of the recessed suppositories described in the specification may be administered into the rectum, vagina, or urethra, including, but not limited to, The method may include inserting the device into any body cavity.

[0009] These and other features of the present disclosure, its nature and various advantages, may be best understood by reference to the accompanying drawings, in which: This will become more apparent upon consideration of the following detailed description. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 is a perspective view of a suppository capsule according to a first embodiment. [Figure 2] FIG. 1 is a top plan view of the first embodiment. [Figure 3] FIG. 2 is a bottom plan view of the first embodiment. [Figure 4] FIG. 2 is a left side view of the first embodiment. [Figure 5] FIG. 2 is a right side view of the first embodiment. [Figure 6] FIG. 1 is a rear view of the distal end of the first embodiment. [Figure 7] FIG. 1 is a front view of the proximal end of the first embodiment. [Figure 8] FIG. 10 is a perspective view of a suppository capsule according to a second embodiment. [Figure 9] FIG. 10 is a top plan view of the second embodiment. [Figure 10] FIG. 10 is a bottom plan view of the second embodiment. [Figure 11] FIG. 10 is a left side view of the second embodiment. [Figure 12] FIG. 10 is a right side view of the second embodiment. [Figure 13] FIG. 10 is a rear view of the distal end of the second embodiment. [Figure 14] FIG. 10 is a front view of the proximal end of the second embodiment. [Figure 15] FIG. 10 is a perspective view of a suppository capsule according to a third embodiment. [Figure 16]FIG. 10 is a top plan view of the third embodiment. [Figure 17] FIG. 10 is a bottom plan view of the third embodiment. [Figure 18] FIG. 10 is a left side view of the third embodiment. [Figure 19] FIG. 10 is a right side view of the third embodiment. [Figure 20] FIG. 10 is a rear view of the distal end of the third embodiment. [Figure 21] FIG. 10 is a front view of the proximal end of the third embodiment. [Figure 22] FIG. 10 is a perspective view of a suppository capsule according to a fourth embodiment. [Figure 23] FIG. 10 is a top plan view of the fourth embodiment. [Figure 24] FIG. 10 is a bottom plan view of the fourth embodiment. [Figure 25] FIG. 10 is a left side view of the fourth embodiment. [Figure 26] FIG. 10 is a right side view of the fourth embodiment. [Figure 27] FIG. 10 is a rear view of the distal end of the fourth embodiment. [Figure 28] FIG. 10 is a front view of the proximal end of the fourth embodiment. [Figure 29] FIG. 10 is a perspective view of a suppository capsule according to a fifth embodiment. [Figure 30] FIG. 10 is a top plan view of the fifth embodiment. [Figure 31] FIG. 10 is a bottom plan view of the fifth embodiment. [Figure 32] FIG. 10 is a left side view of the fifth embodiment. [Figure 33] FIG. 10 is a right side view of the fifth embodiment. [Figure 34] FIG. 10 is a rear view of the distal end of the fifth embodiment. [Figure 35] FIG. 10 is a front view of the proximal end of the fifth embodiment.

[0011] definition As used herein, an "active agent," "a pharmaceutically active ingredient," or "a pharmaceutically active ingredient" refers to a compound or compound that is used for the treatment, prevention, or is intended to have some other intended effect and is used by a government agency for that purpose. Use in the diagnosis, cure, mitigation, treatment, or prevention of any condition, whether or not approved by the These terms for specific drugs refer to all pharmaceutically active agents, All pharmaceutically acceptable salts, stereoisomers, crystalline forms, co-crystals, ethers, esters thereof , hydrates, solvates, and mixtures thereof, which forms are pharmaceutically active.

[0012] The terms "treatment of" and "treating" refer to reducing the severity of a condition or preventing a condition. This includes administering an active agent with the intent to

[0013] The terms "prevention of" and "preventing" include avoiding the onset of a condition.

[0014] The term "condition" or "conditions" refers to a condition in which an effective amount of an active agent is administered. The term "medical condition" refers to those medical conditions that can be treated, alleviated, or prevented by administration to a Exemplary non-limiting conditions that may benefit from the suppository capsules described in include, but are not limited to, pain , migraines, inflammation, fungal infections, bacterial infections, viral infections, vaginal pain, menopause, vulvar and vaginal May include atrophy, cancer, nausea, or vomiting.

[0015] Suppository capsules according to the present disclosure contain various active agents and their pharmaceutically acceptable salts. Pharmaceutically acceptable salts include, but are not limited to, inorganic acid salts, for example, hydrochloride salts. , hydrobromides, sulfates, phosphates, etc.; organic acid salts, for example, formates, acetates, triflate acetates, maleates, tartrates, etc.; sulfonates, e.g., methanesulfonates , benzenesulfonates, p-toluenesulfonates, etc.; amino acid salts, e.g., arginine salts, phosphates, aspartates, glutamates, etc., and metal salts, e.g., sodium salts , potassium salts, cesium salts, etc.; alkaline earth metals, for example, calcium salts, magnesium salts, etc. organic amine salts, such as triethylamine salts, pyridine salts, picoline salts, ethanol salts, etc. Nolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N'-dibenzylamine salt Including benzylethylenediamine salts.

[0016] An "effective amount" or "therapeutically effective amount" is an amount that produces a beneficial or desired effect upon detection of that effect. A pharmaceutical composition sufficient to provide a readily detectable level by commonly used methods ( In some embodiments, such an effect is achieved by administering a suppository or capsule containing the active agent. , resulting in at least a 10% change from the basal level in which no active agent is administered. In certain embodiments, the change is at least 20%, 50%, 80%, or more from basal levels. As discussed below, the effective amount of active agent will vary depending on the age, general condition of the subject, Varies from subject to subject, depending on the severity of the condition being treated, the particular active agent being administered, etc. An appropriate "effective" amount in any individual case may be determined by one of ordinary skill in the art, as described in the relevant texts. and can be determined by reference to the literature and / or using routine experimentation.

[0017] As used herein, a "shell" or "shell composition" refers to a composition that encapsulates a suppository base. This refers to the component of the softgel suppository capsule.

[0018] As used herein, a "suppository base" refers to a substance used as a suppository delivery system. It refers to any suitable pharmaceutically acceptable substance.

[0019] As used herein, a "patient" refers to a person who is suffering from a clinical manifestation of a particular condition or a need for treatment. are experiencing symptoms suggestive of sexual intercourse, are receiving preventative treatment for a condition, or refers to a subject, particularly a human (but may include non-humans), diagnosed with a condition to be treated. vinegar.

[0020] The term "subject" encompasses the definition of the term "patient" and does not exclude otherwise healthy individuals. stomach.

[0021] The terms "suppository," "suppository capsule," and "dosage form" are all used interchangeably throughout this specification. It can be used for.

[0022] As used herein, the singular forms "a," "an," and "the" are used where the context requires. Unless it is clear to the contrary, this includes plural references. Thus, for example, "active Reference to "agent" includes a single active agent and mixtures of two or more different active agents. Reference to includes a single state and a mixture of two or more different states.

[0023] As used herein, the term "about" in connection with a measured quantity means that the measurement can be made and the measurement the measurement to be expected when exercising a level of care commensurate with the purpose and precision of the measuring device. This refers to normal variations in amounts. In certain embodiments, the term "about" refers to "about 10" to 9. 10% of the stated number, so as to include 11%.

[0024] The term "at least about" in reference to a measurable quantity is intended to be interpreted as meaning that the measurement is made by one of ordinary skill in the art and is consistent with the purpose and accuracy of the measurement. the normal variations in measurands that can be expected when exercising a level of care commensurate with the precision of the device; and any amount greater than or equal to 1000 mg / kg. In certain embodiments, the term "at least about" is the number mentioned minus 10%, and "at least about 10" is greater than 9 and 9 The term "about 10 or more" includes any amount greater than the above, so that it would include any amount greater than the above. Similarly, the term "less than about" refers to the referenced number plus 10%, and "about 1 Includes any quantity less than 0, so that "less than 0" would include 11 and anything less than 11. The term can also be expressed as "less than about 10."

[0025] Unless otherwise indicated herein, the recitation of ranges of values ​​herein represents the amount of any value within the range. are only intended to serve as a shorthand way of referring individually to each separate value. and each separate value is incorporated herein as if individually recited herein. Unless otherwise indicated herein or clearly contradicted by context, All methods described herein may be performed in any suitable order.

[0026] The use of any and all examples or exemplary language (e.g., "such as") provided herein The use is intended merely to identify certain materials and methods and is not limited in scope. The language in this specification does not impose any restrictions on the disclosure of any unclaimed material. It should not be construed as indicating a requirement to practice the method. DETAILED DESCRIPTION OF THE INVENTION

[0027] The present disclosure allows for grasping and / or administering the dosage form with one or two fingers. The present invention is directed to a suppository dosage form designed to have at least one cavity. It may also aid in the administration of the dosage form, for example by clarifying the direction in which the suppository should be inserted. The recess is ergonomically designed to allow for comfortable gripping and efficient insertion of the suppository. The depression may be shaped to prevent the suppository from slipping or slipping out of the body cavity. It is also possible.

[0028] The depression is formed by modifying a part of the shape of the dosage form (e.g., one end) to make it possible to fit the existing suppository Shapes (e.g., bullet, tampon, oval, egg, teardrop, torpedo, etc.) can be applied In some embodiments, the grip of the suppository capsule described herein may contain active ingredients present therein. In other embodiments, the suppository capsules described herein may contain at least a portion of the active ingredient. The gripping portion of the roller may not contain an active agent.

[0029] An exemplary recessed suppository capsule is described in detail below with reference to the figures.

[0030] FIG. 1 shows a perspective view of a suppository capsule according to a first embodiment. FIG. FIG. 3 is a top plan view of a suppository according to the embodiment of FIG. 1; FIG. 4 is a bottom plan view of a suppository according to the embodiment of FIG. FIG. 5 is a left side view of the embodiment of FIG. 1. FIG. 6 is a right side view of the embodiment of FIG. 1. As shown in Figure 5, the suppository capsule 100 has a conventional bullet shape at the proximal end 160 and a distal end 170. The distal end 170 may have a dimpled bullet shape such that it has at least one dimple. The bullet shape depicted in Figures 1-5 (cylindrical shape terminating in a dome or cone at the proximal end 160 of the suppository) It should be understood that the above examples are merely illustrative and not limiting. For example, a dome or cone-shaped ending may be more rounded than shown in the embodiment. The cylindrical portion at the proximal end of the bullet-shaped portion may be rounded or more pointed. It can be a cylinder with a constant diameter throughout its length, as shown in The diameter or width of the cylinder may widen or narrow over the entire length of the suppository. (As shown in the dimpled teardrop embodiment described hereinbelow, or (as shown in the recessed oval embodiment described hereinafter).

[0031] In embodiments, the direction of insertion of the suppositories described herein into a body cavity is from the proximal end to the distal end of the suppository. This can be easily seen due to the completely different shape of the end. The proximal end (e.g., 160) is designed to be inserted into the body cavity first, and the distal end (e.g., 170) is designed to be grasped for manual insertion into a body cavity.

[0032] As shown in FIGS. 4 and 5, the suppository capsule 100 is measured along a horizontal axis X. The horizontal axis X and the vertical axis Y may have a length 110 and a width 120 measured along the horizontal axis X and the vertical axis Y. The linear axis Y is shown in Figures 4 and 5. In the embodiment shown in Figures 4 and 5, 20 also corresponds to the diameter of the suppository capsule at the cylindrical portion of the bullet-shaped end of the suppository capsule The length of a suppository (e.g., 110) is the longest dimension of the suppository, measured along its horizontal axis X. The width of the suppository (e.g., 120) is measured along its vertical axis Y. For the first embodiment, the width of the suppository is defined as the widest part of the suppository. and shown in FIG. 5 as numeral 120. In a first embodiment, the width 120 of the suppository is: It also corresponds to the diameter of the cylindrical portion at the proximal end of the bullet shape.

[0033] The length of the suppository capsule measured along its horizontal axis X varies depending on the shape of the suppository capsule. , may vary at different positions along the vertical axis Y. In certain embodiments, The center of a suppository is the longest horizontal portion or dimension of the suppository. In an embodiment, the length of the suppository is the length of the center of the suppository along the vertical Y axis. In this configuration, the horizontal length of the suppository is measured along the vertical Y axis from the center of the suppository to the edge of the suppository. For example, FIGS. 1 to 5 show the first embodiment. In such an embodiment, the water content of the suppository capsule is The horizontal length is measured from edges 130 and 140 (as viewed from the left side view shown in FIG. 4 and FIG. The edge of the suppository capsule along the vertical axis Y when viewed from the right side view shown in 5) is the shortest Preferably, the longest horizontal dimension 110 is the center 150 of the suppository capsule (as shown in FIGS. 4 and 5). The suppository may be gradually increased until it reaches the center of the suppository capsule along the vertical axis Y, as shown in FIG.

[0034] In certain embodiments, the horizontal length 110 of the suppository capsule is between about 10 mm and about 5 mm. 0mm, about 12mm to about 45mm, about 15mm to about 40mm, about 20mm to about 35mm These dimensions are merely examples and should not be construed as limiting.

[0035] The width of the suppository, measured along its vertical axis Y, may also be measured along the horizontal axis X, depending on the shape of the suppository capsule. For example, the suppository of the first embodiment may have a proximal end 16 of the suppository. The suppository capsule may have one width at the distal end 170 of the suppository and another width at the distal end 170 of the suppository. The proximal end 160 may be at one end of the horizontal axis X and the distal end 170 may be at the opposite end of the horizontal axis X. 60 can be adapted for insertion into a body cavity. For example, proximal end 160 can be configured in a conventional suppository shape, e.g. For example, the distal end 170 may have a shape such as, but not limited to, a bullet, an oval, an egg, a teardrop, a torpedo, etc. May be adapted to grip suppository capsules for easy handling and / or administration It may have at least one depression 180 .

[0036] In an embodiment, the length 110 of the suppository capsule is the length of the portion of the suppository having a conventional suppository shape. The length of the suppository (i.e., the length of the bullet shape) plus the length of the portion of the suppository that has the recess The length of the suppository portion having a conventional suppository shape is shown in Figs. The length of the portion of the suppository having at least one recess is shown as length in Figures 4 and 5. Length 112 and length 115 can be combined to form length 110. 112 (i.e., the length of the conventional suppository-shaped portion) and length 115 (the length of the recessed portion) The lengths may be separated by a boundary line 190.

[0037] In certain embodiments, the ratio of length 112 to length 115 is from about 10:1 to about 1: 10, about 8:1 to about 1:8, about 5:1 to about 1:5, about 3:1 to about 1:3, about 2:1 to about 1 :2, about 10:1 to about 1:1, about 8:1 to about 1:1, about 5:1 to about 1:1, about 3:1 to about 1:1, about 2:1 to about 1:1, about 1:1 to about 1:2, about 1:1 to about 1:3, about 1:1 to about The ratio may be in the range of 1:5, about 1:1 to about 1:8, or about 1:1 to about 1:10. The dimensions are for illustration only and should not be construed as limiting.

[0038] In some embodiments, the boundary line 190 between the proximal end 160 and the distal end 170 is such that the suppository is inserted into the body cavity. This may be the widest part of the suppository so as to minimize the possibility of the suppository being expelled. In embodiments, the widest portion of the suppository is along the length 112 (i.e., the width of the suppository, as compared to a conventional suppository shape). In some embodiments, the widest part of the suppository may be on the length 115 (i.e., on the portion of the suppository having at least one depression) good.

[0039] The width of the suppository capsule (e.g., 120) is about 1 mm to about 30 mm, about 2 mm to about 25 mm. These dimensions can range from about 3 mm to about 20 mm, or from about 4 mm to about 15 mm. The Act is illustrative only and should not be construed as limiting.

[0040] In certain embodiments, at least one depression may be flat. In the form, at least one depression is configured to be grasped by at least one finger. It may be concave (i.e., curved inward) to provide an ergonomic fit. In yet another embodiment, the at least one depression may be perforated. In certain embodiments, the at least one At least one recess must be accessible by two fingers or for easy grasping and insertion into a body cavity. The device may be adapted to be clamped by a device for clamping.

[0041] In one embodiment, the distal end 170 is the rear end of the suppository capsule according to the embodiment of FIGS. As shown in the figure (Fig. 6), there may be two recesses 180A and 180B. In such an embodiment, each of the two recesses may be on opposite sides of the distal end. The minimum distance between the boundaries of the dimples can be specified by the number 610 in Figure 6, and ranges from 0 mm to approximately 30 m. m, about 1 mm to about 25 mm, about 2 mm to about 20 mm, about 3 mm to about 15 mm, or These dimensions are merely examples and should not be construed as limiting. It shouldn't be.

[0042] In other embodiments, the distal end of the suppository has one cavity, three cavities, four cavities, five cavities, or In certain embodiments, when there are two or more depressions, In certain embodiments, the depressions may be evenly spaced around the circumference of the distal end of the suppository. When two or more depressions are present, the depressions are equally spaced around the circumference of the distal end of the suppository. It's not necessary.

[0043] FIG. 6 is a rear view of the distal end 170 of the first embodiment of the suppository capsule according to FIGS. 1-5. Two recesses 18 on opposite sides having a minimum distance 610 between their distal end boundaries. 0A and 180B are shown in Figure 6. Figure 7 shows a dome-shaped proximal end with a bullet-shaped proximal end. FIG. 1 is a close-up view of a first embodiment showing a front view of a bullet-shaped suppository with concentric circles to illustrate the shape. FIG. 1 is a front view of the distal end 160.

[0044] FIG. 8 shows a perspective view of a suppository capsule 800 having a concave teardrop shape according to a second embodiment. 15 is a perspective view of a suppository capsule having a concave teardrop shape according to a third embodiment. 22 is a perspective view of a lens 1500 having a dimpled teardrop shape according to a fourth embodiment. suppository capsules 800, 1500, and 2200. 00 are lengths measured along the horizontal axis X and the vertical axis Y, respectively. The suppository may have a width of 800, 1500, 1600, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 6000, 7000, 8000, 9000, 10000, 11000, 12000, 13000, 14000 The lengths of the 2200 and 810 mm are shown in Figs. 11-12 and 1510 mm, respectively. 9), and 2210 (Figs. 25-26). Suppository widths of 800, 1500, and 2200, defined as the widest dimension of the suppository, are width 820 (Figs. 11-12), width 1520 (Figs. 18-19), and width 2220 ( This is shown in Figures 25-26).

[0045] The dimensions of the suppository capsule may vary depending on the shape of the suppository capsule. For example, see Figures 8-12. 15-19, and 22-26 are indented teardrop-shaped suppository capsules according to various embodiments. These suppositories are located at the distal end 870 (Figs. 8-12), 1570 (Figs. 15-19) , and 2270 (Figs. 22-26), the widest widths are 820, 1520, a pointed, elongated proximal end 8 having a width that gradually increases from the proximal end until 2220 is reached; 60 (Figures 8-12), 1560 (Figures 15-19), and 2260 (Figures 22-26). The proximal end 860, 1560, 2260 may be adapted for insertion into a body cavity, while the distal Positions 870, 1570, and 2270 are either at least one recess 880 (FIG. 8) that may be adapted to grip a suppository capsule of 1580 (FIG. 15), 2280 (FIG. 22).

[0046] Suppository capsule lengths of 810, 1510, and 2210 are approximately 10 mm to 50 mm, and approximately 12 mm. The thickness may range from about 15 mm to about 45 mm, from about 15 mm to about 40 mm, or from about 20 mm to about 35 mm. These dimensions are merely illustrative and should not be construed as limiting.

[0047] In the embodiment, the suppository capsules of FIGS. 8-12, 15-19, and 22-26 have a length 810 , 1510, and 2210 are the lengths of the portions of the suppository having a conventional suppository shape (i.e., The length of the suppository (i.e., the length of the teardrop shape) plus the length of the suppository part with the depression. The length of the teardrop-shaped suppository portion is 812 mm (Figs. 11-12), 1 mm (Fig. 512 (Figs. 18-19), length 2215 (Figs. 25-26). The length of the suppository part having two recesses is 815 (Fig. 11-12), 1515 (Fig. 18-19) and length 2215 (Figs. 25-26). Length 812 and length 815 are combined. Combined, the length can be 810. Combined, the length 1512 and the length 1515 can be 15. It can be 10. Length 2212 and length 2215 can be combined to get length 2210. Lengths of 812, 1512, and 2212, respectively (i.e., the lengths of the conventional suppository-shaped portions) length) and their respective lengths of 815, 1515, and 2215 (length of the recessed part) Each of the lines (length) is separated by the corresponding boundaries 890, 1590, and 2290. obtain.

[0048] The ratio of length 812 to length 815 (or the ratio of length 1512 to 1515, or The ratio of length 2212 to 2215 is about 10:1 to about 1:10, about 8:1 to about 1: 8, about 5:1 to about 1:5, about 3:1 to about 1:3, about 2:1 to about 1:2, about 10:1 to about 1 :1, about 8:1 to about 1:1, about 5:1 to about 1:1, about 3:1 to about 1:1, about 2:1 to about 1 :1, about 1:1 to about 1:2, about 1:1 to about 1:3, about 1:1 to about 1:5, about 1:1 to about 1 :8, or in the range of about 1:1 to about 1:10. These dimensions are merely examples. , should not be construed as limiting.

[0049] In some embodiments, boundaries 890, 1590, and 2290 may be configured to prevent the suppository from being expelled from the body cavity. This may be the widest part of the suppository to minimize the chance of expulsion. In this state, the widest part of the suppository is along a length of 812, 1512, or 2212 mm (i.e., In some embodiments, the suppository may be The widest part of the It may also be on the part of the suppository having one depression.

[0050] The width of the suppository capsules 820, 1520, and 2220 is approximately 1 mm to approximately 30 mm, and approximately 2 mm to approximately It may be in the range of about 25 mm, about 3 mm to about 20 mm, or about 4 mm to about 15 mm. These dimensions are merely examples and should not be construed as limiting.

[0051] In certain embodiments, at least one depression in a recessed teardrop-shaped suppository is In other embodiments, at least one of the indented teardrop-shaped suppositories may be flat. The recesses are ergonomically adapted to be grasped by at least one finger. It may be concave (i.e., curved inward), as shown in FIG. In embodiments, at least one cavity in a recessed teardrop-shaped suppository is perforated. Optionally, the slit may have a hole (e.g., a donut hole). In the , at least one depression is accessible by two fingers or for easy grasping and access to the body cavity. It may be adapted to be clamped by a device for insertion.

[0052] In one embodiment, the distal end 870 is formed by two recesses 8 in FIGS. 18, 19, and 20. Similarly, distal end 1570 may have 880A and 880B. 0. Similarly, distal end 2270 may have two depressions 1580A and 1580B. , 25, 26, and 27, may have two depressions 2280A and 2280B. In such an embodiment, each of the two recesses may be on opposite sides of the distal end. The shortest distance between the boundaries of two depressions is 861 (Figs. 11, 12, and 13), 1561 (Figures 18, 19, and 20), or 2261 (Figures 25, 26, and 27) 861, 1561, or 2261 can be set from 0 mm to approximately 30 mm, or approximately 1 mm. ~ about 25 mm, about 2 mm to about 20 mm, about 3 mm to about 15 mm, or any number in between These dimensions are merely examples and should not be construed as limiting.

[0053] In other embodiments, the distal end of the indented teardrop suppository has one indentation, three indentations, , four cavities, five cavities, etc. In certain embodiments, two or more cavities When depressions are present, they may be equally spaced around the circumference of the distal end of the suppository. In certain embodiments, when two or more depressions are present, the depressions are arranged circumferentially around the distal end of the suppository. The distances do not have to be equally spaced.

[0054] Figure 9 is a top plan view of the second embodiment, and Figure 10 is a bottom plan view of the second embodiment. Figure 16 is a top plan view of the third embodiment, and Figure 17 is a bottom plan view of the third embodiment. Figure 23 is a top plan view of the fourth embodiment. Figure 24 is a bottom plan view of the fourth embodiment.

[0055] As shown in FIGS. 9, 10, 16, 17, 23, and 24, the suppository has a proximal end 860 ( 9, 10), 1560 (Figs. 16, 17), or 2260 (Figs. 23, 24). The ocular surface may have a variety of dimpled teardrop shapes, such as those shown in Figures 9, 10, 16, 17, 2 As shown in Figs. 3 and 24, the suppository also has a distal end 870 (Figs. 9, 10), 1570 ( 16, 17), or 2270 (Figs. 23, 24). The illustrated shapes of the proximal and distal ends should not be construed as limiting. Due to the strength of the shell composition (e.g., the strength of the gelatin shell composition), many It is possible to realize a suppository form.

[0056] Figure 11 is a left side view of the second embodiment. Figure 12 is a right side view of the second embodiment. Figure 18 is a left side view of the third embodiment. Figure 19 is a right side view of the third embodiment. Figure 25 is a left side view of the fourth embodiment. Figure 26 is a right side view of the fourth embodiment. Figures 11, 12, 18, 19, 25, and 26 show various types of suppositories from different angles. 1 shows a teardrop shape with a possible dimple.

[0057] 13 is a rear view of the distal end 870 of the second embodiment. Two depressions 880A and 880B on opposite sides with a short distance 861 are shown in FIG. FIG. 14 shows a front view of the teardrop-shaped suppository at the proximal end 86 of the second embodiment. This is a front view of 0.

[0058] 20 is a rear view of the distal end 1570 of the third embodiment. Two recesses 1580A and 1580B on opposite sides with a minimum distance 1561 20. FIG. 21 is a close-up view of a third embodiment showing a front view of a teardrop-shaped suppository. FIG. 15 is a front view of the distal end 1560.

[0059] 27 is a rear view of the distal end 2270 of the fourth embodiment. Two recesses 2280A and 2280B on opposite sides with a minimum distance 2261 27. FIG. 28 is a close-up view of a fourth embodiment showing a front view of a teardrop-shaped suppository. FIG. 22 is a front view of the distal end 2260.

[0060] FIG. 29 shows a suppository capsule 2900 having a concave oval shape according to a fifth embodiment. The suppository capsule 2900 has a length measured along a horizontal axis X and a vertical axis X. The suppository may have a width measured along the longitudinal axis Y. The width is defined as the longest horizontal dimension of the suppository. , the length of the suppository 2900 measured along its horizontal axis X is represented as length 2910 The widest dimension of the suppository 2900 measured along its vertical axis Y is represented as width 2920. will be done.

[0061] The dimensions of the suppository capsule may vary depending on the shape of the suppository capsule. For example, FIG. The proximal end 2960 represents a suppository capsule having an oval shape with a concave shaped portion. while the distal end 2970 may be adapted to a suppository for easy handling and / or administration. It may have at least one recess 2980 that may be adapted to grip a capsule.

[0062] The length of the suppository capsule is about 10 mm to about 50 mm, about 12 mm to about 45 mm, about These dimensions can range from 15 mm to about 40 mm, and from about 20 mm to about 35 mm. These are illustrative examples and should not be construed as limiting.

[0063] In an embodiment, the length 2910 of the suppository capsule is equal to the length of the portion of the suppository having a conventional suppository shape. The length (i.e., the length of the oval shape) plus the length of the part of the suppository that has a depression The length of the suppository portion having an oval shape is represented as length 2912. The length of the portion of the suppository having at least one recess is represented as length 2915. Length 2912 and length 2915 can be combined to form length 2910. That is, the length of the conventional suppository-shaped portion) and length 2915 (the length of the recessed portion) are , may be separated by a boundary line 2990.

[0064] The ratio of length 2912 to length 2915 is about 10:1 to about 1:10, about 8:1 to about 1 :8, about 5:1 to about 1:5, about 3:1 to about 1:3, about 2:1 to about 1:2, about 10:1 to about 1:1, about 8:1 to about 1:1, about 5:1 to about 1:1, about 3:1 to about 1:1, about 2:1 to about 1:1, about 1:1 to about 1:2, about 1:1 to about 1:3, about 1:1 to about 1:5, about 1:1 to about 1:8, or in the range of about 1:1 to about 1:10. These dimensions are merely examples. and should not be construed as limiting.

[0065] In some embodiments, the boundary line 2990 minimizes the possibility of the suppository being expelled from the body cavity. In some embodiments, the widest part of the suppository may be the widest part of the suppository. The portion is located along the length 2912 (i.e., on the portion of the suppository having a conventional suppository shape). In some embodiments, the widest portion of the suppository is along the length 2915 (i.e., on the portion of the suppository having at least one depression).

[0066] For example, in FIG. 29, which shows a recessed oval suppository according to the fifth embodiment, The widest part of the suppository is along the ellipse (i.e., along the length 2912) and the suppository is This may minimize the chance of expulsion from the cavity.

[0067] The diameter of the suppository capsule is about 1 mm to about 30 mm, about 2 mm to about 25 mm, about 3 These dimensions can range from about 1 mm to about 20 mm, or from about 4 mm to about 15 mm. These are illustrative examples and should not be construed as limiting.

[0068] In certain embodiments, at least one recess in a recessed oval suppository is In other embodiments, at least one of the indented oval suppositories may be flat. One recess is ergonomically adapted to be grasped by at least one finger It may be concave (i.e., curved inward), as shown in FIG. In this embodiment, at least one cavity in the recessed oval suppository is perforated. Optionally, the periphery may have a hole (e.g., a donut hole). In this state, at least one depression is provided for easy grasping and insertion by two fingers or into the body cavity. The device may be adapted to be clamped by a device for insertion of the device.

[0069] In one embodiment, the distal end 2970 has two recesses as shown in FIGS. 2980A and 2980B. In such an embodiment, each of the two recesses The depressions may be on opposite sides of the distal end. The shortest distance between the boundaries of two depressions is the number 296. It can be specified as 1. Distance 2961 can be set from 0 mm to approximately 30 mm, or from approximately 1 mm to approximately 25 m. mm, about 2 mm to about 20 mm, about 3 mm to about 15 mm, or any number in between. These dimensions are for illustrative purposes only and should not be construed as limiting.

[0070] In other embodiments, the distal end of the indented teardrop suppository has one indentation, three indentations, , four cavities, five cavities, etc. In certain embodiments, two or more cavities When depressions are present, they may be equally spaced around the circumference of the distal end of the suppository. In certain embodiments, when two or more depressions are present, the depressions are arranged circumferentially around the distal end of the suppository. The distances do not have to be equally spaced.

[0071] Figure 30 is a top plan view of the fifth embodiment. Figure 31 is a bottom plan view of the fifth embodiment. As shown in Figures 30 and 31, the suppository has an oval shape at the proximal end 2960 and a It may have a dimpled oval shape such that 2970 has at least one dimple.

[0072] Figure 32 is a left side view of the fifth embodiment. Figure 33 is a right side view of the fifth embodiment. Figures 32 and 33 also show the concave oval shape of the suppository from different angles.

[0073] 34 is a rear view of the distal end 2970 of the fifth embodiment. Two recesses 2980A and 2980B on opposite sides with a shortest distance 2961 34. FIG. 35 is a close-up view of a fifth embodiment showing a front view of an oval-shaped suppository. FIG. 29 is a front view of the distal end 2960.

[0074] The suppository shapes shown are a bullet shape with a dimple, a teardrop shape with three different dimples, and a concave oval shape, but other concave suppository capsule shapes are also contemplated. For example, the present disclosure relates to, but is not limited to, dimpled bullets, Dimpled tampons, dimpled ovals (e.g., dimpled ellipses or dimpled Includes shapes such as round-oval, dimpled oval, dimpled teardrop, and dimpled torpedo. obtain.

[0075] The suppository capsule allows for the construction of the recessed suppository shapes described herein. Suppository bases may include, but are not limited to, cocoa butter, lard, or other suppository bases that may be sturdy enough to withstand the effects of suppository administration. Urin-based oils and fats, beef tallow, hard fat, theobroma oil, glycerides of fatty acids, glycerol-ze The suppository base may comprise one or more of a liquid form, a hydroxypropyl methylcellulose base ... In one embodiment, the suppository base is administered to the extracorporeal periphery. It can be in a solid form at ambient temperature and melts into a liquid form upon insertion of the suppository into a body cavity. To achieve this, the core body temperature (for example, about 30°C to about 45°C, about 33°C to about 42°C, about 35°C) The melting point may be between about 37°C and about 40°C.

[0076] The suppository may encapsulate a suppository base (e.g., in a core and shell configuration). In certain embodiments, the active agent is dispersed entirely throughout the suppository base. In other embodiments, the active agent may be dispersed in a particular portion of the suppository base. It may be dispersed in the suppository base, and may not be dispersed in its entirety throughout the suppository base. In embodiments, the active agent is located in at least one recessed area for easy gripping of the suppository. and the like, are not dispersed throughout the suppository base in at least a portion of the distal end of the suppository capsule. That's fine.

[0077] Core and Shell Formulation In certain embodiments, the suppository capsule may have a core and shell structure, and the active ingredient The agent may be contained only in the core, only in the shell, or in both the core and the shell. In one embodiment, the active agent may be contained only in the core. In one embodiment, the active agent is contained in both the core and the shell. It is possible to have the active agent in the core, shell, or both. The active agent may be dispersed throughout the entire particle or at least in part (e.g., in the core, shell, etc.). , or both distal portions).

[0078] In one embodiment, the distal portion of the suppository may be flat with at least one depression. The adhesive may be free of an active agent, allowing for the formation of a smooth, flat "gripping area." In the present invention, the active agent is positioned in the cavity so that at least one depression can form a concave "grasping area." It may be dispersed throughout the suppository, including in at least one recess in the distal end of the suppository. The shape of the "grasping area" or depression of the suppository allows for the active agent or part of the suppository to be dispersed throughout the suppository. designed to accommodate the dispersing active agent (e.g., when the distal end of the suppository does not contain the active agent). These embodiments are merely illustrative, as various modifications may be made.

[0079] In certain embodiments, the shell has at least one recess ("container") in the distal portion of the suppository. "easy grip") and allows for the construction of conventional suppository shapes in the proximal portion of the suppository. In some embodiments, the core (or suppository base) may be sufficiently sturdy to accommodate the distal portion of the suppository. at least one recess in the portion (for "easy grip"), and a conventional In some embodiments, the suppository shape may be constructed from a suppository of the same size. The gel may include, but is not limited to, gelatin, starch, modified starch, carrageenan, alginate, etc. The composition may include at least one of an acid salt, a biodegradable polymer, or a combination thereof.

[0080] In certain embodiments, the shell composition comprises gelatin. Gelatin can be, but is not limited to, may include Type A gelatin, Type B gelatin, or a mixture thereof. gelatin, including but not limited to fish gelatin, hide gelatin, bone gelatin, or mixtures thereof. The gelatin may comprise from about 40% w / w to about 80% w / w based on the total weight of the shell composition. w, about 45% w / w to about 75% w / w, or about 50% w / w to about 70% w / w The amount of hydroxybenzoates present in the shell may be in the range of 0.1 to 1.0 wt.

[0081] In certain embodiments, the shell composition comprises carrageenan. Carrageenans include κ-carrageenan, ι-carrageenan, λ-carrageenan, and their It may be a mixture. According to one embodiment, the carrageenan is kappa-carrageenan. According to an embodiment, the carrageenan is ι-carrageenan. The amount of carrageenan in the shell composition is about 2% w / w to about 1% w / w based on the total weight of the shell composition. 0% w / w, about 2% w / w to about 8% w / w, or about 2% w / w to about 5% w / w.

[0082] In certain embodiments, the shell composition comprises a biodegradable polymer. Examples of the polymers include, but are not limited to, polylactic acid (PLA), poly(ε-caprolactone) (PCL), poly poly(lactide-co-glycolic acid) (PLGA), or a combination thereof.

[0083] In certain embodiments, the shell may be made of, but is not limited to, glycerol, sorbitol, Other suitable plasticizers include, but are not limited to, plasticizers such as acrylic acid, acrylic acid esters ... However, sugar alcohol plasticizers, such as isomalt, maltitol, xylitol, Thuritol, adonitol, dulcitol, pentaerythritol, or mannitol or polyol plasticizers, such as diglycerin, ethylene glycol, diethylene glycol Recall, triethylene glycol, tetraethylene glycol, dipropylene glycol polyethylene glycol, neopentyl glycol, propyl glycol, up to 10,000 MW ethylene glycol, 1,3-propanediol, 2-methyl-1,3-propanediol, Trimethylolpropane, polyether polyols, ethanolamines; and their Other exemplary plasticizers include, but are not limited to, low molecular weight polymers, oligomers, and mixtures thereof. mers, copolymers, oils, small organic molecules, low molecular weight polyols with aliphatic hydroxyls, Ester plasticizers, glycol ethers, poly(propylene glycol), multiblock copolymers, single block polymers, citrate ester plasticizers, and triacetyl Such plasticizers may also include 1,2-butylene glycol, 2,3-butylene glycol, and the like. Recall, styrene glycol, monopropylene glycol monoisopropyl ether, Propylene glycol monoethyl ether, ethylene glycol monoethyl ether, di Ethylene glycol monoethyl ether, sorbitol lactate, ethyl lactate, butyl lactate, Ethyl glycolate, dibutyl sebacate, acetyltributyl citrate, tricitric acid Ethyl, glyceryl monostearate, polysorbate 80, citric acid Acetyl triethyl, tributyl citrate and allyl glycolate, and their The plasticizer may comprise from about 15% w / w to about 40% w / w of the total weight of the shell composition. % w / w, about 20% w / w to about 35% w / w, or about 25% w / w to about 30% w / w It may be present in the shell in a range of amounts.

[0084] In one embodiment, the suppository may have a core and shell structure, where the core comprises a suppository base. In certain embodiments, the core may be solid at ambient temperature and may be heated to body core temperature (e.g., For example, about 30°C to about 45°C, about 33°C to about 42°C, about 35°C to about 40°C, or about 37°C. In other embodiments, the core may be liquid at ambient temperature.

[0085] activator Suitable active agents that may be contained in the suppository capsules described herein include, but are not limited to, analgesics drugs, anti-migraine drugs, anti-inflammatory drugs, antifungal drugs, antibiotics, antiviral drugs, hormones, chemotherapy drugs, It may include an anti-nausea agent, an anti-emetic agent, or a combination thereof.

[0086] Exemplary analgesic active agents include, but are not limited to, acetaminophen and opioids. Exemplary opioids include, but are not limited to, alfentanil, allylprodine, and alfentanil. Rufaprozine, Anileridine, Benzylmorphine, Bezitramide, Buprenorphine, Butorphanol, clonitazene, codeine, desomorphine, dextromethorphan, desomorphine Dihydrocodeine, diampromide, diamorphone, dihydrocodeine, dihydromo Ruhine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxane butyrate Fetyl, Dipipanone, Eptazocine, Ethoheptazine, Ethylmethylthiambutene, Ethylmethylthiambutene Tilmorphine, etonitazene, etorphine, dihydroetorphine, fentanyl and and derivatives, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone ketobemidone, levorphanol, levophenacylmorphan, lofentanil, Peridine, meptazinol, metazocine, methadone, metopon, morphine, myrofin, Narceine, Nicomorphine, Norlevorphanol, Normethadone, Nalorphine, Nalu Buphine, normorphine, norpipanone, opium, oxycodone, oxymorphone, paclitaxel Paveretam, Pentazocine, Phenadoxone, Phenomorphan, Phenazocin, Pheno Peridine, piminodine, piritramide, propeptadine, promedol, properidine , propoxyphene, sufentanil, tilidine, tramadol, and their pharmaceutically acceptable The salts may include those which are prepared by the method of the present invention, and combinations thereof.

[0087] Exemplary antimigraine active agents include, but are not limited to, ergotamine, dihydroergotamine, Ergostine, butalbital, phenobarbital, sumatriptan, naratriptan , razatriptan, zolmitriptan, almotriptan, eletriptan valproic acid, gabapentin, topiramate, divalproex, The compound may contain pharmaceutically acceptable salts thereof or mixtures thereof.

[0088] Exemplary anti-inflammatory active agents include, but are not limited to, ibuprofen, fenoprofen, naproxen, Loxene, sulindac, diclofenac, piroxicam, ketoprofen, diflunisal , nabumetone, etodolac, oxaprozin, indomethacin, and their pharmaceutically acceptable salts The compound may contain a salt or mixtures thereof.

[0089] Exemplary antifungal agents include, but are not limited to, abafungin, albaconazole, amorol fin, amphotericin b, anidulafungin, bifonazole, butenafine, b Toconazole, candicidin, caspofungin, ciclopirox, clotrimazole , econazole, fenticonazole, philippines, fluconazole, flucytosine, g Riseofulvin, Haloprogin, Hamycin, Isavuconazole, Isoconazole, Ito Laconazole, ketoconazole, micafungin, miconazole, naftifine, natama Isin, nystatin, omoconazole, oxiconazole, polygodial, posacona azole, ravuconazole, rimocidin, sertaconazole, sulconazole terbinafine, terconazole, tioconazole, tolnaftate ), undecylenic acid, voriconazole, pharmaceutically acceptable salts thereof or mixtures thereof It may contain a mixture.

[0090] Exemplary antibiotics include, but are not limited to, mitomycin, ciprofloxacin, norfloxacin, and thiazolinone. Floxacin, ofloxacin, methanamine, nitrofurantoin, Ampicillin, amoxicillin, nafcillin, trimethoprim, sulfa drugs trimethoprim Sulfamethoxazole, erythromycin, doxycycline, metronidazole, Tetracycline, kanamycin, penicillin, cephalosporin, aminoglycoside, It may include pharmaceutically acceptable salts thereof or mixtures thereof.

[0091] Exemplary antiviral active agents include, but are not limited to, abacavir, acyclovir, adefovir, Amprenavir, Atazanavir, Cidofovir, Darunavir, Delavir Din, didavines, didanosine, docosanol, efavirenz, Elvite Erbitegra, emtricitabine, entravirin, famciclovir ir), foscarnet, fomivirsen, ganciclovir, indinavir, iodoxuridi lan, lamivudine, nelfinavir, nevirapine, penciclovir, ral Tegravir, rilpivirine, rilupavirin, ritonavir, saquinavir, Stavudine, tenofovir, trifluridine, valacyclovir, valganciclovir, vidamin rafamin, ibasitabine, tipranavir, zalcitabine, zidovudine, and their pharmaceutically acceptable salts The compound may include any acceptable salt and mixtures thereof.

[0092] Exemplary hormonally active agents include, but are not limited to, estradiol and its pharmaceutically acceptable salts. Additional hormonally active agents include, but are not limited to, progesterone and and pharmaceutically acceptable salts thereof.

[0093] Exemplary anti-nausea active agents include, but are not limited to, metoclopramide, prochlorperazine, Domperidone, ondansetron, tropisetron, dolasetron, nabilone, dronabi Nol, levonantradol, aprepitant, cyclizine, promethazine, and those drugs The compound may include physiologically acceptable salts and mixtures thereof.

[0094] Exemplary antiemetic active agents include, but are not limited to, chlorpromazine, dimenhydrinate (di menhydrinate), dolasetron, dronabinol, granisetron, meclizine, methoxamer metocloproamide, ondansetron, perphenazine, prochlorperazine perazine, promethazine, scopolamine, thiethylperazine, trimethobenzamide, The compound may include pharmaceutically acceptable salts thereof and mixtures thereof.

[0095] excipients In some embodiments, the suppositories described herein contain a pharmaceutically acceptable excipient or carrier. The term "pharmaceutically acceptable excipient or carrier" refers to, for example, a pharmaceutical agent that can be used to transport an active ingredient. Refers to any inactive ingredient in a composition that may act to stabilize it. Excipients that can be used include, but are not limited to, carbohydrates (glucose, sucrose, or decanoate). anti-oxidants (d-α-tocopherol, ascorbic acid, or glutathione) ions, chelating agents, low molecular weight proteins, high molecular weight polymers, gel-forming agents, or Other stabilizers and additives may be included. Other examples of pharmaceutically acceptable carriers include wetting agents (e.g., lecithin), emulsifiers, surfactants and / or dispersing agents (e.g., polysorbates ( polysorbate)80), alkalis, colorants, synthetic dyes, fillers, diluents, mineral oxides or or a preservative, which are particularly useful for preventing the growth or action of microorganisms. Various preservatives are well known and include, for example, phenol and ascorbic acid. Examples of stabilizers, stabilizers or adjuvants are listed in Remington's Pharmaceutical Sciences, Mack Publishing ng Company, Philadelphia, Pa., 17th ed. (1985).

[0096] Suitable antioxidants include, but are not limited to, sterically hindered phenols, arylamines, thiol Urea, thiocarbamate, phosphite, thioether ester, and combinations of the foregoing Other suitable examples of antioxidants include alkylated monophenols, such as Examples include, but are not limited to, 2,6-di-tert-butyl-4-methylphenol, 2-te rt-Butyl-4,6-dimethylphenol, 2,6-di-tert-butyl-4-ethoxyphenol 2,6-di-tert-butyl-4-n-butylphenol, 2,6- Di-tert-butyl-4-isobutylphenol, 2,6-dicyclopentyl-4-methylphenol 2-(α-methylcyclohexyl)-4,6-dimethylphenol, 2 ,6-Dioctadecyl-4-methylphenol, 2,4,6-Tricyclohexylphenol 2,6-di-tert-butyl-4-methoxymethylphenol, or branched nonylphenols, e.g., 2,6-di-nonyl-4-methylphenol; 2,4-dimethyl-6-(1'-methylundec-1'-yl)phenol, 2,4 -Dimethyl-6-(1'-methylheptadec-1'-yl)phenol, 2,4-dimethyl 1-(1'-methyltridec-1-yl)phenol and their mixtures, thiomethylphenols, such as, but not limited to, 2,4-dioctylthiomethylphenols; 2,4-dioctyl-6-tert-butylphenol, 2,4-dioctylthiomethyl-6-methylphenol phenol, 2,4-dioctylthiomethyl-6-ethylphenol, 2,6-di-dodecyl Thiomethyl-4-nonylphenol, hydroquinone and alkylated hydroquinones, e.g. For example, but not limited to, 2,6-di-tert-butyl-4-methoxyphenol 2,5-di-tert-butylhydroquinone, 2,5-di-tert-amylhydroquinone Quinone, 2,6-diphenyl-4-octadecyloxyphenol, 2,6-di-tert-butyl t-butylhydroquinone, 2,5-di-tert-butyl-4-hydroxyanisole, 3,5-di-tert-butyl-4-hydroxyanisole, 3,5-di-tert-butyl butyl-4-hydroxyphenyl stearate, bis(3,5-di-tert-butyl-4 -hydroxyphenyl) adipate, tocopherol, for example, but not limited to , α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol and mixtures thereof (vitamin E), hydroxylated thiodiphenyl ethers, e.g. , but not limited to, 2,2'-thiobis(6-tert-butyl-4-methylfuran) phenol), 2,2'-thiobis(4-octylphenol), 4,4'-thiobis(6 -tert-butyl-3-methylphenol), 4,4'-thiobis(6-tert-butyl 4,4'-thiobis(3,6-di-sec-amylphenol) 4,4'-bis(2,6-dimethyl-4-hydroxyphenyl)-disulfide alkylidene bisphenols, such as, but not limited to, 2,2'-methyl 2,2'-methylenebis(6-tert-butyl-4-methylphenol), -tert-butyl-4-ethylphenol), 2,2'-methylenebis[4-methyl- 6-(α-methylcyclohexyl)-phenol], 2,2'-methylenebis(4-methyl 2,2'-methylenebis(6-nonyl-4-methylphenol) 2,2'-methylenebis(4,6-di-tert-butylphenol) , 2,2'-ethylidenebis(4,6-di-tert-butylphenol), 2,2'- Ethylidenebis(6-tert-butyl-4-isobutylphenol), 2,2'-methyl Benzyl-6-(α-methylbenzyl)-4-nonylphenol, 2,2'-methylene Bis[6-(α,α-dimethylbenzyl)-4-nonylphenol], 4,4'-methyl 4,4'-methylenebis(6-t ert-butyl-2-methylphenol), 1,1-bis(5-tert-butyl-4- Hydroxy-2-methylphenyl)butane, 2,6-bis(3-tert-butyl-5- Methyl-2-hydroxybenzyl)-4-methylphenol, 1,1,3-tris(5- tert-Butyl-4-hydroxy-2-methylphenyl)butane, 1,1-bis(5- tert-Butyl-4-hydroxy-2-methyl-phenyl)-3-n-dodecyl mercapto Butanol, ethylene glycol bis[3,3-bis(3'-tert-butyl-4'- hydroxyphenyl) butyrate], bis(3-tert-butyl-4-hydroxy-5 -methyl-phenyl)dicyclopentadiene, bis[2-(3'-tert-butyl-2 '-Hydroxy-5'-methylbenzyl)-6-tert-butyl-4-methylphenyl ] terephthalate, 1,1-bis-(3,5-dimethyl-2-hydroxyphenyl) butadiene 2,2-bis(3,5-di-tert-butyl-4-hydroxyphenyl)propane , 2,2-bis(5-tert-butyl-4-hydroxy-2-methylphenyl)-4- n-Dodecylmercaptobutane, 1,5,5-tetra-(5-tert-butyl-4-hydroxybenzoyl) (hydroxy-2-methylphenyl)pentane, O-, N- and S-benzyl compounds, e.g. For example, but not limited to, 3,5,3',5'-tetra-tert-butyl-4,4 '-Dihydroxydibenzyl ether, octadecyl-4-hydroxy-3,5-dimethyl Benzyl mercaptoacetate, tridecyl-4-hydroxy-3,5-di-tert -butyl benzyl mercaptoacetate, tris(3,5-di-tert-butyl-4- Hydroxybenzyl)amine, Bis(4-tert-butyl-3-hydroxy-2,6- dimethylbenzyl)dithioterephthalate, bis(3,5-di-tert-butyl-4- Hydroxybenzyl) sulfide, isooctyl-3,5-di-tert-butyl-4- Hydroxybenzyl mercaptoacetate, hydroxybenzylated malonate, e.g., These include, but are not limited to, dioctadecyl-2,2-bis(3,5-di-tert-butyl) Dioctadecyl-2-(3-tert-butyl)malonate (4-hydroxy-5-methylbenzyl) malonate, didodecylmercaptoethyl -2,2-bis(3,5-di-tert-butyl-4-hydroxybenzyl)malonate , bis[4-(1,1,3,3-tetramethylbutyl)phenyl]-2,2-bis(3, 5-di-tert-butyl-4-hydroxybenzyl) malonate, aromatic hydroxybenzyl benzyl compounds, such as, but not limited to, 1,3,5-tris(3,5-di-t ert-butyl-4-hydroxybenzyl)-2,4,6-trimethylbenzene, 1,4 -Bis(3,5-di-tert-butyl-4-hydroxybenzyl)-2,3,5,6- Tetramethylbenzene, 2,4,6-tris(3,5-di-tert-butyl-4-hydro (hydroxybenzyl)phenol, triazine compounds, such as, but not limited to, 2 ,4-bis(octylmercapto)-6-(3,5-di-tert-butyl-4-hydrogen xyanilino)-1,3,5-triazine, 2-octylmercapto-4,6-bis(3 ,5-di-tert-butyl-4-hydroxyanilino)-1,3,5-triazine, 2 -octylmercapto-4,6-bis(3,5-di-tert-butyl-4-hydroxy phenoxy)-1,3,5-triazine, 2,4,6-tris-(3,5-di-tert -butyl-4-hydroxyphenoxy)-1,2,3-triazine, 1,3,5-tris (3,5-di-tert-butyl-4-hydroxybenzyl)isocyanurate, 1,3 ,5-Tris(4-tert-butyl-3-hydroxy-2,6-dimethylbenzyl)iso Socyanurate, 2,4,6-tris-(3,5-di-tert-butyl-4-hydroxybenzoate) 1,3,5-tris(3,5-diphenylethyl)-1,3,5-triazine, 1,3,5-tris(3,5-di-te rt-Butyl-4-hydroxyphenylpropionyl)-hexahydro-1,3,5- Triazine, 1,3,5-tris(3,5-dicyclohexyl-4-hydroxybenzyl) ) iso-cyanurate, benzyl phosphonate, for example, but not limited to, dimethicone Diethyl-2,5-di-tert-butyl-4-hydroxybenzylphosphonate -3,5-di-tert-butyl-4-hydroxybenzylphosphonate, dioctadecyl 3,5-di-tert-butyl-4-hydroxybenzylphosphonate, dioctade sil-5-tert-butyl-4-hydroxy-3-methylbenzylphosphonate, 3, Monoethyl ester of 5-di-tert-butyl-4-hydroxybenzylphosphonic acid calcium salts, acylaminophenols, such as, but not limited to, 4-hydroxybenzoates, Xylanilide, 4-hydroxystearanilide, octyl N-(3,5-di-t ert-butyl-4-hydroxyphenyl)carbamate, β-(3,5-di-tert -butyl-4-hydroxyphenyl)propionic acid with monohydric or polyhydric alcohols, e.g. For example, methanol, ethanol, n-octanol, i-octanol, octadecanoic acid 1,6-Hexanediol, 1,9-Nonanediol, Ethylene Glycol, 1,2 -Propanediol, neopentyl glycol, thiodiethylene glycol, diethylene Glycol, triethylene glycol, pentaerythritol, tris(hydroxyethyl) N,N'-bis(hydroxyethyl)oxamide, 3-thiaun Decanol, 3-thiapentadecanol, trimethylhexanediol, trimethylol Propane, 4-hydroxymethyl-1-phospha-2,6,7-trioxabicyclo[2 .2.2]octane, β-(5-tert-butyl-4-hydroxy-3- methylphenyl)propionic acid with monohydric or polyhydric alcohols, for example methanol, Ethanol, n-octanol, i-octanol, octadecanol, 1,6-hexa Nonanediol, 1,9-nonanediol, ethylene glycol, 1,2-propanediol , neopentyl glycol, thiodiethylene glycol, diethylene glycol, triethylene glycol Ethylene glycol, pentaerythritol, tris(hydroxyethyl) isocyanurate N,N'-bis-(hydroxyethyl)oxamide, 3-thiaundecanol, 3- Thiapentadecanol, trimethylhexanediol, trimethylolpropane, 4-hydroxybenzoates Hydroxymethyl-1-phospha-2,6,7-trioxabicyclo[2.2.2]octa 3,9-bis[2-{3-(3-tert-butyl-4-hydroxy-5-methylphenyl] (phenyl)propionyloxy}-1,1-dimethylethyl]-2,4,8,10-tetra Ester with oxaspiro[5.5]-undecane, 6-(3,5-dicyclohexyl- 4-hydroxyphenyl)propionic acid with monohydric or polyhydric alcohols, e.g., alcohol, ethanol, octanol, octadecanol, 1,6-hexanediol, 1 ,9-nonanediol, ethylene glycol, 1,2-propanediol, neopentyl Glycol, thiodiethylene glycol, diethylene glycol, triethylene glycol Pentaerythritol, Tris(hydroxyethyl)isocyanurate, N,N'- Bis(hydroxyethyl)oxamide, 3-thiaundecanol, 3-thiapentadecanol ethanol, trimethylhexanediol, trimethylolpropane, 4-hydroxymethyl- Esters with 1-phospha-2,6,7-trioxabicyclo[2.2.2]octane, 3,5-Di-tert-butyl-4-hydroxyphenylacetic acid and monohydric or polyhydric alcohols with, for example, methanol, ethanol, octanol, octadecanol, 1,6- Hexanediol, 1,9-nonanediol, ethylene glycol, 1,2-propanediol O ethanol, neopentyl glycol, thiodiethylene glycol, diethylene glycol, thiazolinone Polyethylene glycol, pentaerythritol, tris(hydroxyethyl)isocyanuric acid ester, N,N'-bis(hydroxyethyl)oxamide, 3-thiaundecanol, 3 -Thiapentadecanol, trimethylhexanediol, trimethylolpropane, 4- Hydroxymethyl-1-phospha-2,6,7-trioxabicyclo[2.2.2]octyl Ester with tannin, 6-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate Amides of propionic acid, such as N,N'-bis(3,5-di-tert-butyl-4-hydroxybenzoates) N,N'-bis(3,5-dihydroxyphenylpropionyl)hexamethylenediamide -tert-butyl-4-hydroxyphenylpropionyl)trimethylenediamide, N ,N'-bis(3,5-di-tert-butyl-4-hydroxyphenylpropionyl) Hydrazide, N,N'-bis[2-(3-[3,5-di-tert-butyl-4-hydro [(2- ... XL-1, manufactured by Uniroyal), ascorbic acid (vitamin C), amine antioxidants, For example, but not limited to, N,N'-di-isopropyl-p-phenylenediamine N,N'-di-sec-butyl-p-phenylenediamine, N,N'-bis(1,4 -dimethylpentyl)-p-phenylenediamine, N,N'-bis(1-ethyl-3-methyl- N,N'-bis(1-methylheptyl)-p-phenylenediamine -Phenylenediamine, N,N'-dicyclohexyl-p-phenylenediamine, N,N '-Diphenyl-p-phenylenediamine, N,N'-bis(2-naphthyl)-p-phenyl N-isopropyl-N'-phenyl-p-phenylenediamine, N-( 1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine, N-(1-methyl -p-phenylenediamine, N-cyclohexyl-N'- Phenyl-p-phenylenediamine, 4-(p-toluenesulfamoyl)diphenylamine amine, N,N'-dimethyl-N,N'-di-sec-butyl-p-phenylenediamine, Diphenylamine, N-allyldiphenylamine, 4-isopropoxydiphenylamine , N-phenyl-1-naphthylamine, N-(4-tert-octylphenyl)-1- Naphthylamine, N-phenyl-2-naphthylamine, octylated diphenylamine, e.g. For example, but not limited to, p,p'-di-tert-octyldiphenylamine, 4-n-butylaminophenol, 4-butyrylaminophenol, 4-nonanoylaminophenol 4-Dodecanoylaminophenol, 4-Octadecanoylaminophenol bis(4-methoxyphenyl)amine, 2,6-di-tert-butyl-4-dimethylamine methylaminomethylphenol, 2,4'-diaminodiphenylmethane, 4,4'-diamino N,N,N',N'-tetramethyl-4,4'-diaminodiphenylmethane methylmethane, 1,2-bis[(2-methylphenyl)amino]ethane, 1,2-bis(phenyl (o-tolyl)biguanide, bis[4-(1',3'-dimethylamino)propane butyl)phenyl]amine, tert-octylated N-phenyl-1-naphthylamine, Mono- and di-alkylated tert-butyl / tert-octyldiphenyl mixture of mono- and di-alkylated nonyldiphenylamines, Mixture of mono- and di-alkylated dodecyldiphenylamine, mono- and di-alkylated dodecyldiphenylamine and a mixture of dialkylated isopropyl / isohexyl diphenylamines, monoalkyl Mixture of alkylated and dialkylated tert-butyldiphenylamines, 2,3-dihydro- 3,3-dimethyl-4H-1,4-benzothiazine, phenothiazine, monoalkylated and and mixtures of dialkylated tert-butyl / tert-octylphenothiazines, mono Mixture of alkylated and dialkylated tert-octyl-phenothiazines, N-aliphatic Ruphenothiazine, N,N,N',N'-tetraphenyl-1,4-diaminobut-2- and combinations of the foregoing.

[0097] Suitable alkaline agents include, but are not limited to, magnesium oxide, ammonium hydroxide, hydroxide Sodium chloride, sodium carbonate, sodium citrate, trisodium phosphate and / or may include disodium phosphate.

[0098] Suitable colorants include, but are not limited to, white, black, yellow, blue, green, Colors may include pink, red, orange, violet, indigo, and brown. The color of the dosage form may indicate the contents (e.g., one or more active agents) contained therein.

[0099] Suitable lubricants / release agents include, but are not limited to, fatty acids and their salts, fatty alcohols, may include fatty esters, fatty amines, fatty amine acetates, and fatty amides. Other suitable lubricants include, but are not limited to, glyceryl behenate (Comprit ol (trademark) 888), metallic stearates (e.g., stearic acid Magnesium stearate, calcium stearate, and sodium stearate), stearic acid Phosphoric acid, hydrogenated vegetable oil (e.g., Sterotex™), talc, beeswax, and potassium Waxes such as lunauba wax, silica, fumed silica, colloidal silica, stearyl calcium phosphate, long chain fatty alcohol, boric acid, sodium benzoate and sodium acetate cereals, sodium chloride, DL-leucine, polyethylene glycol (e.g., Carbohydrate ax™ 4000 and Carbowax™ 6000), sodium oleate , Sodium Benzoate, Sodium Acetate, Sodium Lauryl Sulfate, Stearyl Fumarate Sodium Lauryl Sulfate (Pruv®), Magnesium Lauryl Sulfate, Stearic Acid, Sodium Lauryl Sulfate Tearyl alcohol, mineral oil, paraffin, microcrystalline cellulose, glycerin, propylene glycol recall, and combinations thereof.

[0100] Suitable bulking agents / antiblocking agents / detackifying agents include, but are not limited to, starch modified starch, cross-linked polyvinylpyrrolidone, cross-linked cellulose, microcrystalline cellulose, The additives may include calcium carbonate, metal oxides, calcium carbonate, talc, and mica.

[0101] Suitable diluents include, but are not limited to, lactose USP, lactose USP (without Water), Lactose USP (Spray-dried), Starch USP, Directly Compressible Starch , Mannitol USP, Sorbitol, Dextrose Monohydrate, Microcrystalline Cellulose NF , Dibasic Calcium Phosphate Dihydrate NF, Sucrose-Based Diluent, Powdered Sugar, Monobasic Calcium sulfate monohydrate, calcium sulfate dihydrate NF, calcium lactate trihydrate granules NF, dextrate NF (e.g., Emdex™), dextro (e.g., Cerelose™), inositol, Maltrons™ and hydrolyzed cereal solids, amylose, powders such as Mor-Rex™ Cellulose (e.g., Elcema™), calcium carbonate, glycine, bentonite Polyvinylpyrrolidone, etc.

[0102] Exemplary oils and fats include, but are not limited to, almond oil, argan oil, avocado oil, and celery oil. Corn oil, canola oil, cashew oil, castor oil, cocoa butter, palm oil, rapeseed oil, corn Koshi oil, cottonseed oil, grapeseed oil, hazelnut oil, hemp oil, hydroxylated lecithin, lecithin , flaxseed oil, macadamia oil, mango oil, manila oil, mongo nut oil, olive oil, paprika Corn kernel oil, palm oil, peanut oil, pecan oil, perilla oil, pine nut oil, pistachio Oil, poppy seed oil, pumpkin seed oil, rice bran oil, safflower oil, sesame oil, shea butter, soybean oil May contain sunflower oil, walnut oil, and watermelon seed oil. PVA shell filling contains Other oils and fats that may be used include, but are not limited to, fish oil (omega-3), krill oil, For example, animal or vegetable fats in their hardened form, C12-, C14-, C16-, C18- Monoglycerides, diglycerides, and triglycerides containing C-, C20-, and C22- fatty acids It may contain lysides.

[0103] Exemplary pH adjusters include, but are not limited to, hydrochloric acid, potassium hydroxide, sodium hydroxide, The acid may include sodium, ammonium hydroxide, sulfuric acid, phosphoric acid, and nitric acid.

[0104] Other exemplary excipients include, but are not limited to, vegetable proteins, such as sunflower oil. Protein, soybean protein, cottonseed protein, peanut protein, grape seed Protein, whey protein, whey protein isolate, blood protein, egg protein Proteins, acrylated proteins, water-soluble polysaccharides, e.g., alginates, carrageenans, Guar gum, agar, xanthan gum, gellan gum, gum arabic and similar gums ( Gum ghatti, gum karaya, gum tragacanth), pectin, water-soluble derivatives of cellulose Alkyl cellulose, hydroxyalkyl cellulose, and hydroxyalkyl cellulose cellulose, such as methylcellulose, hydroxymethylcellulose, hydroxy Ethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methyl cellulose , hydroxypropyl methylcellulose, hydroxybutyl methylcellulose, cellulose cellulose esters and hydroxyalkyl cellulose esters, such as cellulose acetate hydroxypropyl methylcellulose (HPMC); Dialkyl cellulose, carboxyalkyl alkyl cellulose, carboxyalkyl cellulose cellulose esters, such as carboxymethylcellulose and their alkali metal salts; Water-soluble synthetic polymers, such as polyacrylic acid, polyacrylamide, and polyacrylamides Polymethacrylic acid esters, polymethacrylamides, and polymethacrylic acid esters ter, polyvinyl acetate, polyvinyl alcohol, polyvinyl acetate phthalate (PV AP), polyvinylpyrrolidone (PVP), PVY / vinyl acetate copolymer, and poly Crotonic acid; also suitable are phthalated gelatin, gelatin succinate (gela tin succinate), cross-linked gelatin, shellac, water-soluble chemical derivatives of starch, e.g. Cationic modified cationically modified amines having tertiary or quaternary amino groups, such as ethylaminoethyl groups. acrylic and methacrylic acid salts (optionally quaternized); and Other similar polymers; inorganic fillers, e.g., magnesium, aluminum, silicon, titanium The oxides may include fluorine and the like.

[0105] Other pharmaceutically acceptable excipients include, but are not limited to, hydrophobic substances, such as Not limited to, but includes natural or synthetic waxes (e.g., beeswax, glycowax) ), castor wax, and carnauba wax) 2-C40) substituted or unsubstituted hydrocarbons, fatty alcohols (e.g., lauryl, myristyl stearyl, cetyl, or preferably cetostearyl alcohol), fatty acids, e.g. including, but not limited to, medium chain fatty acids (e.g., caprylic acid, capric acid, caproic acid, Mono- and diglycerides of fatty acids (lauric acid, oleic acid, linoleic acid), medium chain triglycerides, Fatty acid esters, fatty acid glycerides (monoglycerides, diglycerides, and triglycerides) Lid), hydrogenated fats, hydrocarbons, ordinary waxes, stearic acid, stearyl alcohol, and hydrophobic and hydrophilic substances having a hydrocarbon backbone.

[0106] Additional pharmaceutically acceptable excipients include polyvinyl alcohol, polyvinylpyrrolidone, Polyalkylene oxide, polyacrylic acid, cellulose, cellulose ether, cellulose esters, cellulose amides, polyvinyl acetate, polycarboxylic acids and salts, acetic acid, caprylic / capric triglycerides, oleic acid, polyamino acids or peptides, polyamides, polyacrylamides, Maleic / acrylic acid copolymers, polysaccharides such as starch and gelatin, xanthan For example, the polymer may further comprise a natural gum such as polyacrylamide gel, polysorbate 80, polysorbate 85, polysorbate 86, polysorbate 87, polysorbate 88, polysorbate 89, polysorbate 90, polysorbate 91, polysorbate 92, polysorbate 95, polysorbate 96, polysorbate 97, polysorbate 98, polysorbate 99, polysorbate 99 acrylate and water-soluble acrylate copolymer, methylcellulose, carboxymethylcellulose Sodium cellulose, dextrin, ethyl cellulose, hydroxyethyl cellulose, Hydroxypropyl methylcellulose, maltodextrin, polymethacrylate, and and combinations thereof, or polyvinyl alcohol, polyvinyl a Alcohol copolymer and hydroxypropyl methylcellulose (HPMC), methacrylate Methacrylic acid / methyl methacrylate, methacrylic acid / ethyl acrylate copolymer, methacrylic acid / Methyl acrylate / methyl methacrylate copolymer, shellac, hydroxypropyl Methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate cellulose acetate, hydroxypropyl methylcellulose trimellitate, cellulose acetate lid acrylate, polyvinyl acetate phthalate, PEG-35 castor oil, caprylocaproyl Polyoxyl-8 glyceride, glyceryl distearate, and combinations thereof You can choose.

[0107] Suitable high HLB surfactants include, but are not limited to, polysorbate 80 -Polyoxyethylene (20) sorbitan monooleate, polyoxyl 40 hydrogenated castor Oil, Polyoxyl 35 Castor Oil, Caprylocaproyl Macrogolglycerides, and It may include combinations of these.

[0108] Exemplary fillers include, but are not limited to, lactose, microcrystalline cellulose, and the like. The compound may be selected from the group consisting of:

[0109] In some embodiments, the excipients, individually or cumulatively, comprise about 100% by weight of the total suppository. 90w / w% or less, approx. 80w / w% or less, approx. 70w / w% or less, approx. 60w / w% or less, approx. 50w / w% or less, approx. 40w / w% or less, approx. 30w / w% or less, approx. 20w / w% or less, approx. 15w / w% or less, approximately 10w / w% or less, approximately 5w / w% or less, approximately 4w / w% or less, approximately 3w / w% or less, approximately 2w / w% or less, approximately 1w / w% or less, approximately 0.5w / w% or less, approximately 0.1w In some embodiments, the suppository may be present in a concentration of up to 1 / wt% of the total weight of the suppository. For example, about 2 w / w% to about 50 w / w%, about 6 w / w% to about 50 w / w%, individually or in total. Approx. 40w / w%, approx. 10w / w% to approx. 30w / w%, approx. 10w / w% to approx. 40w / w%, Approx. 15w / w%~Approx. 35w / w%, Approx. 20w / w%~Approx. 30w / w%, Approx. 20w / w%~ The excipient may be present in an amount of about 25 w / w%, or in a range of about 15 w / w% to about 25 w / w%. .

[0110] Preparation method In some embodiments, the present disclosure is directed to a method of preparing any of the suppositories described herein. The method may include forming the suppository base into a suppository. With reference to Figures 1-7, The suppository has a length 110 measured along the horizontal axis X, and a width 110 measured along the vertical axis Y. 20 and may be formed such that the length 110 is greater than the width 120. The proximal end 160 may be formed to have a proximal end 160 and a distal end 170 along X. The distal end 170 may be configured to be adapted for insertion into a body cavity. During manual insertion (whether manual insertion is performed with a finger or an applicator) It has at least one recess for easy gripping of the suppository so that it does not slip off. The "gripping area" at the distal end of the suppository allows the user to orient the suppository in the desired direction. (i.e., the proximal end enters the body cavity first). The shape of the "grasping area" of the suppository makes it difficult for the suppository to be expelled from the body cavity.

[0111] Similarly, the method may involve dissolving the suppository base in the form of a suppository base as shown in Figures 8-35, which are described in more detail hereinabove. The dimensions (length and / or diameter) and proximal and distal shapes are as shown in The method may include forming the compound into a suppository having the formula:

[0112] The method for preparing any of the suppositories described herein may include administering any of the active agents contemplated herein. In some embodiments, the active agent may further comprise dispersing either the active agent or the active agent in a suppository base. In other embodiments, the active agent may be dispersed entirely throughout the suppository base. For example, in one embodiment, the active agent may be dispersed in only a portion of the suppository base. The core and shell structure may not be dispersed in at least a portion of the distal end of the base. In the prepared embodiment, the preparation method may include placing the active ingredient only in the core, only in the shell, or in the core alone. The step of dispersing the cellulose in both the core and the shell may be included.

[0113] In certain embodiments, the method of preparing a suppository includes applying a shell onto a suppository base. In one embodiment, the method further comprises forming a core and a shell structure. Shell suppositories can be prepared by immersing a core in a shell composition. The shell composition may be solid at ambient temperature and may be immersed in a liquid shell composition.

[0114] In one embodiment, the core and shell suppository has a liquid containing suppository base enclosed in the shell. For example, the core may be liquid and may be prepared by stamping (rotary stamping). The encapsulation may be carried out at ambient temperature or by other suitable means such as stamping. For example, for ease of processing and handling, The encapsulation can also be carried out at temperatures above ambient when the solution is liquid. In embodiments, the core, which is liquid at an encapsulation temperature above ambient temperature, may solidify at ambient temperature. and melts again when inserted into a body cavity (i.e., exposed to human core temperature). There is.

[0115] In some embodiments, the suppository base is formed by rotary die stamping the suppository base (including the active agent). The suppository base may be encapsulated using rotary die encapsulation. having a mold designed to form a recessed suppository capsule shape such as that described above. Conventional rotary die equipment can be used. Similarly, for core and shell suppository constructions, The encapsulation of the core into a shell by rotary die encapsulation can be achieved by using a dimpled die such as those described herein. A conventional rotary die apparatus is used having a die designed to form a suppository capsule shape. It is possible.

[0116] According to embodiments, any of the suppository capsules disclosed herein comprises: (a) preparing a suppository base; (b) combining the suppository base of step (a) with an active agent to form a core; and optionally (c) a shell composition comprising the combined suppository base and active agent. The composition may be prepared by a process comprising the step of applying the composition onto a core.

[0117] Preparing the suppository base according to step (a) may involve the addition of a plurality of pharmaceutically acceptable excipients or or a carrier.

[0118] In certain embodiments, step (b) may include mixing the active agent with a suppository base. In another embodiment, step (b) comprises using a rotary die encapsulation process to encapsulate the active agent. and encapsulating the compound in a suppository base to form a filled suppository base in the shape of a recessed suppository. do.

[0119] In certain embodiments, step (c) comprises premixing the cores from step (b). In another embodiment, step (c) may comprise immersing the surface of the substrate in a shell composition prepared by: encapsulating the core from step (b) in a shell composition using a rotary die encapsulation process; This may include forming a recessed suppository shape having a core and shell structure.

[0120] Treatment method In some embodiments, the present disclosure provides any of the suppositories described herein to a person in need thereof. The present invention may be directed to a method of treating a disease or condition by administering the compound to a body cavity of a patient.

[0121] The step of administering the suppository includes grasping the suppository in at least one recess at a distal end of the suppository. The grasping / holding of the suppository may be performed with at least one finger. In some embodiments, grasping the suppository is performed with two fingers, three fingers, four fingers, In certain embodiments, grasping the suppository may be performed with one or more fingers. This may be done using tools such as a suction cup, forceps, etc. In other embodiments, grasping the suppository may be performed. This can be done without the use of tools such as applicators, forceps, etc.

[0122] In certain embodiments, the step of administering the suppository comprises administering the suppository via the proximal end (i.e., Inserting the suppository into a body cavity (e.g., by hand) (i.e., with the proximal end inserted first) The body cavity may be, but is not limited to, the rectum, vagina, or urethra, and may further include a seat The agent may accordingly be adapted for vaginal, rectal, or urethral insertion.

[0123] Exemplary diseases or conditions that can be treated with any of the suppositories described herein are limited to: Not limited to, but includes pain, migraines, inflammation, fungal infections, bacterial infections, viral infections, vaginal pain, menopause These may include vaginal atrophy, nausea, vomiting, or a combination thereof.

[0124] The suppositories described herein may be used to provide a localized therapeutic effect, a systemic therapeutic effect, or a localized therapeutic effect. This can have both therapeutic and systemic effects.

[0125] In the foregoing description, specific materials, dimensions, processes, etc. are used in order to provide a thorough understanding of the present invention. Many specific details are given, such as process, parameters, etc. Or features may be combined in any suitable manner in one or more embodiments. The word "example" or "exemplary" means serving as an example, instance, or illustration. Any reference herein to an "example" or "exemplary" Any aspect or design of any kind is not necessarily preferred or advantageous over other aspects or designs. Rather, the use of the words "example" or "exemplary" should not be interpreted as specifically referring to As used in this application, the term "or" is intended to be used interchangeably. " is intended to mean an inclusive "or" rather than an exclusive "or" That is, unless otherwise specified or clear from the context, "X is A or "Containing B" is intended to mean any of the natural inclusive permutations, i.e. X contains A; X contains B; or X contains both A and B, then "X is either A or B" "In one embodiment," "including," "a particular References throughout this specification to "an embodiment" or "one embodiment" relate to that embodiment. It is understood that any particular feature, structure, or characteristic described herein may be included in at least one embodiment. Accordingly, the phrase "in one embodiment" in various places throughout this specification Appearances of "," "a particular embodiment," or "one embodiment" do not necessarily all refer to the same embodiment. It does not refer to the form.

[0126] The present invention has been described with reference to specific exemplary embodiments thereof. The description and drawings are to be regarded in an illustrative rather than a restrictive sense. Various modifications of the invention in addition to those shown and described will become apparent to those skilled in the art. It is intended to fall within the scope of the appended claims. [Explanation of symbols]

[0127] 100 suppository capsules 110 length 112 length 115 length 120 width 130 Edge 140 Edge 150 center 160 proximal end 170 distal end 180 depression 180A recess 180B recess 190 Borderline 800 suppository capsules 810 length 812 length 815 length 820 width 860 proximal end 870 distal end 880 depression 880A recess 880B recess 890 Borderline 1500 suppository capsules 1510 length 1512 length 1515 length 1560 proximal end 1570 distal end 1580 hollow 1580A recess 1580B recess 1590 Border 2200 suppository capsules 2210 length 2212 length 2215 length 2220 width 2260 Proximal end 2261 Shortest distance 2270 Distal end 2280 hollow 2280A recess 2280B recess 2290 Border 2900 suppository capsules 2910 length 2912 length 2915 length 2920 width 2920 diameter 2960 proximal end 2970 distal end 2980 hollow 2980A recess 2980B hollow 2990 Borderline

Claims

1. A suppository comprising a suppository base, the suppository having a width measured along the horizontal axis that is greater than the width measured along the vertical axis. a proximal end along said horizontal axis adapted for insertion into a body cavity; and a distal end along said horizontal axis having at least one recess.

2. 10. The suppository of claim 1 further comprising an active agent.

3. 3. The suppository of claim 2, wherein the active agent is dispersed in the suppository base.

4. 4. The suppository of claim 2 or 3, wherein the active agent is dispersed entirely throughout the suppository base. Suppositories listed above.

5. The active agent is dispersed throughout the suppository base in at least a portion of the distal end. The suppository according to claim 2 or 3, wherein the suppository is not a suppository.

6. 6. The suppository of claim 1, wherein the distal end has two recesses.

7. 7. The suppository of claim 6, wherein each recess is on opposite sides of the distal end.

8. At least one of the recesses is adapted for gripping with at least one finger. The suppository according to any one of claims 1 to 7.

9. dimpled bullet, dimpled oval, dimpled oval, dimpled teardrop, or 9. The method according to claim 1, wherein the torpedo has a shape selected from the group consisting of a torpedo with a dimple. Suppositories.

10. 10. The method of claim 1, wherein at least one of the depressions is flat. Suppositories.

11. 10. The method of claim 1, wherein at least one of the depressions is concave. Suppositories.

12. 10. The method according to claim 1, wherein at least one of the depressions is perforated. Suppositories.

13. 13. A suppository according to any one of claims 1 to 12, having a core and shell structure.

14. An active agent is contained in the core, the shell, or both the core and the shell.

14. The suppository according to claim 13.

15. 15. The suppository of claim 13 or 14, wherein the core comprises the suppository base.

16. The shell may be made of gelatin, starch, modified starch, carrageenan, alginate, biodegradable 13 to 15, comprising at least one of a degradable polymer, a degradable polymer, or a combination thereof.

16. A suppository according to any one of claims 15.

17. The shell comprises a biodegradable polymer, and the biodegradable polymer is polylactic acid (PLA). ), poly(ε-caprolactone) (PCL), poly(lactide-co-glycolic acid) ( 17. The suppository of claim 16, wherein the suppository is selected from the group consisting of PEG-100, PEG-110, PEG-120, PEG-130, PEG-140, PEG-150, PEG-160, PEG-170, PEG-180, PEG-190, PEG-200, PEG-210, PEG-220, PEG-230,

18. The suppository base is selected from the group consisting of cocoa butter, lauric fat, beef tallow, hard fat, theobroma oil, and fatty acids. glyceride, glycerol-gelatin base, or a combination thereof 18. A suppository according to any one of claims 1 to 17, comprising one.

19. 18. A suppository according to any one of claims 13 to 17, wherein the core is solid at ambient temperature. 。

20. 18. A suppository according to any one of claims 13 to 17, wherein the core is liquid at ambient temperature. 。

21. 21. The suppository of claim 1, wherein the suppository base has a melting point at body temperature. 。

22. 22. Any of claims 1 to 21 adapted for vaginal, rectal, or urethral insertion. The suppository according to claim 1.

23. 23. A suppository according to any one of claims 1 to 22, which provides a localized therapeutic effect.

24. 24. A suppository according to any one of claims 1 to 23, which provides a systemic therapeutic effect.

25. The active agent may be an analgesic, anti-migraine, anti-inflammatory, antifungal, antibiotic, antiviral, phosphatase, or the like.

25. The method of claim 2, wherein the compound is selected from the group consisting of a steroid, a chemotherapeutic agent, an anti-nausea agent, and an anti-emetic agent. The suppository according to any one of claims 1 to 4.

26. The active agent comprises an analgesic, and the analgesic is acetaminophen or an opioid.

26. The suppository of claim 25.

27. The active agent comprises an antimigraine agent, and the antimigraine agent is selected from the group consisting of ergotamine, dihydroergomethicone, and benzodiazepine. thiamin, ergostine, butalbital, phenobarbital, sumatriptan, nalatriptan Triptan, razatriptan, zolmitriptan, almotriptan, eletriptan, fluproic acid, gabapentin, topiramate, divalproex, and these drugs 26. The suppository of claim 25, wherein the suppository is selected from a physiologically acceptable salt, or a mixture thereof.

28. The active agent comprises an anti-inflammatory agent, and the anti-inflammatory agent is ibuprofen, fenoprofen , naproxen, sulindac, diclofenac, piroxicam, ketoprofen, Diflu Nisal, nabumetone, etodolac, oxaprozin, indomethacin, and their pharmaceutical 26. The suppository of claim 25, wherein the suppository is selected from an acceptable salt, or a mixture thereof.

29. The active agent comprises an antifungal agent, and the antifungal agent is abafungin, albaconazole , amorolfine, amphotericin b, anidulafungin, bifonazole, butena Fin, butoconazole, candicidin, caspofungin, ciclopirox, cloto Rimazole, Econazole, Fenticonazole, Philippines, Fluconazole, Flucy Tocin, griseofulvin, haloprogin, hamycin, isavuconazole, isoconazo methicillin, itraconazole, ketoconazole, micafungin, miconazole, naftifϊ natamycin, nystatin, omoconazole, oxiconazole, polygodial , posaconazole, ravuconazole, rimocidin, sertaconazole, sulconazole, Terbinafine, terconazole, tioconazole, tolnaftate, indecylenic acid, voriconazole, a pharmaceutically acceptable salt thereof, or a mixture thereof 26. The suppository of claim 25, wherein the suppository is selected from:

30. The active agent comprises an antibiotic, the antibiotic being selected from the group consisting of mitomycin, ciprofloxacin, norfloxacin, ofloxacin, methanamine, nitrofurantoin, ampicillin, Amoxicillin, nafcillin, trimethoprim, sulfa drugs trimethoprim-sulfamethoxazole Toxazole, erythromycin, doxycycline, metronidazole, tetracycline Phosphorus, kanamycin, penicillin, cephalosporins, aminoglycosides, and their pharmaceuticals 26. The suppository of claim 25, wherein the suppository is selected from a physiologically acceptable salt or a mixture thereof.

31. The active agent comprises an antiviral agent, and the antiviral agent is abacavir, acyclovir , adefovir, amprenavir, atazanavir, atazanavir, cidofovir, darunavir , delavirdine, didabine, didanosine, docosanol, efavirenz, elvitegra , emtricitabine, entravirine, famciclovir, foscarnet, fomivir ganciclovir, indinavir, idoxuridine, lamivudine, nelfinavir, Nevirapine, penciclovir, raltegravir, rilpivirine, rilpavirine, ritonavir fluvir, saquinavir, stavudine, tenofovir, trifluridine, valacyclovir, valgan Ciclovir, vidarabine, ibacitabine, tipranavir, zalcitabine, zidovudine, and 26. The compound according to claim 25, selected from the group consisting of pharmaceutically acceptable salts thereof and mixtures thereof. Suppositories.

32. The active agent comprises a hormone agent, and the hormone agent is estradiol or a 26. The suppository of claim 25, wherein the suppository is a physiologically acceptable salt.

33. The active agent comprises an anti-nausea agent, and the anti-nausea agent is metoclopramide, prochlorperazine, Gin, domperidone, ondansetron, tropisetron, dolasetron, nabilone, lonabinor, levonantradol, aprepitant, cyclizine, promethazine, or a pharmaceutically acceptable salt thereof, Suppositories.

34. The active agent comprises an antiemetic agent, and the antiemetic agent is chlorpromazine, dimenhydrinate, (dimenhydrinate), dolasetron, dronabinol, granisetron, meclizine, Toclopramide, ondansetron, perphenazine, prochlorperazine, promethazine scopolamine, thiethylperazine, trimethobenzamide, and their pharmaceutically acceptable salts 26. The suppository of claim 25, wherein the suppository is selected from the group consisting of benzodiazepines, benzodiazepines, benzoyl benzoates ...

35. 18. The method of claim 13, wherein the core is prepared by dipping the core into a shell composition.

21. A suppository according to any one of claims 19 or 20.

36. 13 or 14, which is prepared by encapsulating a liquid containing the suppository base in the shell.

21. A suppository according to any one of claims 17, 19 or 20.

37. 37. The suppository of claim 36, wherein the encapsulating comprises stamping.

38. 38. The suppository of claim 37, wherein the stamping comprises rotary die stamping.

39. 39. A method according to any one of claims 36 to 38, wherein the encapsulation is carried out at a temperature above ambient temperature. The suppository described.

40. 40. The suppository of claim 39, wherein the liquid solidifies at ambient temperature.

41. 17. The suppository of claim 16, wherein the shell composition further comprises a plasticizer.

42. the plasticizer is selected from glycerol, sorbitol, or a mixture thereof; 42. The suppository of claim 41.

43. The shell composition comprises gelatin, and the gelatin is selected from the group consisting of Type A gelatin, Type B gelatin, and the like.

17. The suppository of claim 16, wherein the suppository is selected from the group consisting of benzoyl perfluorooctanoate, ...

44. The shell composition comprises gelatin, and the gelatin is selected from the group consisting of fish gelatin, animal skin gelatin, and bone gelatin.

17. The suppository of claim 16, wherein the suppository is selected from the group consisting of hydroxybenzoates, ...

45. The shell composition comprises from about 40 wt % to about 80 wt %, about 45 wt% to about 75 wt%, or about 50 wt% to about 70 wt% of gelatin. Item 16 or any one of items 41 to 44, the suppository.

46. The shell composition comprises from about 15 wt % to about 40 wt % of the total weight of the shell composition. , about 20 wt % to about 35 wt %, or about 25 wt % to about 30 wt % of a plasticizer.

43. The suppository according to claim 41 or 42.

47. Inserting the suppository of any one of claims 1 to 46 into a body cavity of a patient in need thereof.

20. A method of treating a disease or condition, comprising:

48. 48. The method of claim 47, wherein the body cavity is the rectum, vagina, or urethra.

49. The disease or condition is pain, migraine, inflammation, fungal infection, bacterial infection, viral infection, vaginal infection, pain, menopausal symptoms, vulvar and vaginal atrophy, cancer, nausea, or vomiting.

49. The method according to claim 47 or 48.

50. the inserting step includes manually holding the suppository in at least one recess; and 50. The method of any one of claims 47 to 49, comprising inserting the suppository by hand. Law.

51. 1. A method of preparing a suppository comprising forming a suppository base into a suppository, said suppository comprising: a length along a horizontal axis that is greater than a width along a vertical axis, and the suppository is a proximal end along the horizontal axis adapted to The method has a distal end along a slab axis.

52. 52. The method of claim 51, further comprising dispersing an active agent in the suppository base. 。

53. applying a shell onto the suppository base to form a core and shell structure.

53. The method of claim 51 or 52.

54. The active agent is contained in the core, the shell, or the core and the shell of the suppository.

54. The method of any one of paragraphs 51 to 53.

55. The applying step comprises immersing the suppository base in a shell composition to form the core and shell.

54. The method of claim 53, comprising forming a hol structure.

56. The applying step encapsulates a liquid containing the suppository base in the shell to form the core and and forming a shell structure.

57. 57. The method of claim 56, wherein the encapsulating comprises stamping.

58. 58. The method of claim 57, wherein the stamping comprises rotary die stamping.

59. 59. Any of claims 56 to 58, wherein the encapsulating is performed at a temperature above ambient temperature.

1. The method according to claim 1.

60. 60. The method of any one of claims 56 to 59, wherein the liquid solidifies at ambient temperature.

61. 61. The method of claim 60, wherein the solidified liquid melts at human core temperature.

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