Sustained release peptide formulations

Abstract

The present disclosure provides, at least in part, a pharmaceutical product comprising: sememartide (also referred to as RM493); sametastide as the sole active pharmaceutical ingredient formulated for injection; as the sole active ingredient, sememartide; as an active pharmaceutical ingredient, sememarin; as an active pharmaceutical ingredient for injection; or another pharmaceutical composition having a major mechanism of action of an MC4 receptor agonist (referred to herein as MC4 RAP), such as a lipid excipient, and / or a pharmaceutically acceptable carrier. The pharmaceutical products described herein provide for sustained release of sememarin or another pharmaceutical composition, which, upon administration, can result in more desirable pharmacokinetic and pharmacodynamic characteristics.

Description

[0001] This application is a divisional application of Chinese invention patent application filed on November 15, 2018, with application number 201880086481.9 and invention title "Sustained-release peptide formulation".

[0002] Priority requirements

[0003] This application claims priority to U.S. Application No. 62 / 586,643, filed November 15, 2017, the entire contents of which are incorporated herein by reference. Background Technology

[0004] Many biological compounds are rapidly released after administration in standard formulations. Therefore, there is a need to develop formulations with extended release that can prolong the duration of the compound in circulation and provide the desired pharmacokinetic and pharmacodynamic properties. Summary of the Invention

[0005] This disclosure provides at least a portion of a pharmaceutical product comprising: cymelanide (also known as RM493); cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or an MC4 receptor agonist (referred to herein as MC4RA) as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P Another pharmaceutical composition relating to the main mechanism of action of MC4 receptor agonists, such as BIM-22511 (also known as RM511), BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or the MC4 receptor agonist comprising SEQ ID NO: 11 as disclosed in WO 2008 / 147556 (hereinafter referred to as MC4R-11). The pharmaceutical product comprises lipid excipients, alcohols, and polar solvents, or combinations thereof, in varying molar ratios. The pharmaceutical product may also comprise a pharmaceutically acceptable carrier, such as ceramide peptide (or MC4RA). P Compared to the administration of ) alone, the pharmaceutical products described herein provide, for example, pharmacologically active cermelan peptides (or MC4RA) P Sustained release, such as gradual or prolonged release, allows the drug product to achieve more desirable pharmacokinetic and pharmacodynamic characteristics after administration.

[0006] In one aspect, this disclosure provides a pharmaceutical product comprising: a) a neutral diacyllipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0007] In another aspect, this disclosure provides a pharmaceutical product comprising: a) a neutral diacyl lipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) cermelan peptide.

[0008] In another aspect, this disclosure provides a pharmaceutical product comprising: a) a neutral diacyl lipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) a cermelan peptide as the sole active ingredient.

[0009] In another aspect, this disclosure provides a pharmaceutical product comprising: a) a neutral diacyl lipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) cermelan peptide as an active pharmaceutical ingredient.

[0010] In another aspect, this disclosure provides a pharmaceutical product comprising: a) a neutral diacyl lipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) cermelan peptide as an active pharmaceutical ingredient for injection.

[0011] On the other hand, this disclosure provides a pharmaceutical product comprising: a) a neutral diacyllipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) MC4RA. P For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11.

[0012] On the other hand, this disclosure provides a pharmaceutical product comprising: a) a neutral diacyllipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) MC4RA as the sole active ingredient. P For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11.

[0013] On the other hand, this disclosure provides a pharmaceutical product comprising: a) a neutral diacyllipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) MC4RA as the sole active ingredient for injection. P For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11.

[0014] On the other hand, this disclosure provides a pharmaceutical product comprising: a) a neutral diacyllipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) MC4RA as an active pharmaceutical ingredient. PFor example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11.

[0015] On the other hand, this disclosure provides a pharmaceutical product comprising: a) a neutral diacyllipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) MC4RA as an active pharmaceutical ingredient for injection. P For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11.

[0016] In an example, component a) of the composition comprises a neutral diacyl lipid. In an example, the neutral diacyl lipid comprises diglyceride. In an example, the neutral diacyl lipid comprises glyceryl dioleate (GDO).

[0017] In one embodiment, component b) of the composition comprises phosphatidylcholine. In another embodiment, the phospholipid comprises soybean phosphatidylcholine.

[0018] In the examples, component c) of the composition comprises ethanol. In the examples, the ethanol is provided in a sufficiently large amount to provide solubility of at least 10 mg / g, 20 mg / g, or 30 mg / g of cermelan peptide.

[0019] In an embodiment, component d) of the composition comprises a polar solvent, such as a buffer solution, for example, a citrate buffer, optionally wherein the pH of the buffer solution is 6.4. In an embodiment, the polar solvent, such as the buffer solution, comprises citrate monohydrate. In another embodiment, the polar solvent, such as the buffer solution, comprises additional components, such as an antioxidant or a chemical or physical stabilizer. In an embodiment, the antioxidant is EDTA. In an embodiment, the polar solvent, such as the buffer solution, comprises citrate monohydrate, disodium EDTA, and water.

[0020] In the embodiments, component e) of the composition comprises ceremonitrile; ceremonitrile as the sole active pharmaceutical ingredient formulated for injection; or MC4RA. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In the examples, component e) of the composition comprises cermelan peptide.

[0021] In the embodiments, component e) provides cermelan peptide as the sole active ingredient.

[0022] In the embodiments, component e) provides cermelan peptide as an active pharmaceutical ingredient.

[0023] In the embodiments, component e) provides cermelan peptide as an active pharmaceutical ingredient for injection.

[0024] In the embodiments, component e) provides MC4RA as the sole active ingredient. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0025] In the embodiment, component e) provides MC4RA as the sole active ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0026] In the embodiments, component e) provides MC4RA as an active pharmaceutical ingredient. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0027] In the embodiment, component e) provides MC4RA as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0028] In an example, the composition comprises: a neutral diacyl lipid containing dioleoglyceride; a phospholipid containing phosphatidylcholine; an alcohol containing ethanol; a polar solvent, such as a buffer containing, for example, a citrate buffer containing EDTA at pH 6.4; and ceramide peptide.

[0029] In the examples, the composition comprises, per milliliter of the composition, 419.8 mg of glyceryl dioleate (GDO); 419.8 mg of soybean phosphatidylcholine; 105 mg of ethanol; 20 mg of citrate buffer; and 30 mg of ceramide peptide.

[0030] On the other hand, this disclosure provides an injectable pharmaceutical product comprising: a) a neutral diacyllipid and / or tocopherol; b) a phospholipid; c) an alcohol; d) optionally, a polar solvent, such as a buffer, which optionally contains an antioxidant; and e) a cermelan peptide or MC4RA. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0031] In the embodiments, component e) provides cermelan peptide as the sole active ingredient.

[0032] In the embodiments, component e) provides cermelan peptide as an active pharmaceutical ingredient.

[0033] In the embodiments, component e) provides cermelan peptide as an active pharmaceutical ingredient for injection.

[0034] In the embodiments, component e) provides MC4RA as the sole active ingredient. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0035] In the embodiment, component e) provides MC4RA as the sole active ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0036] In the embodiments, component e) provides MC4RA as an active pharmaceutical ingredient. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0037] In the embodiment, component e) provides MC4RA as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0038] In an example, component a) of the composition comprises a neutral diacyl lipid. In an example, the neutral diacyl lipid comprises diglyceride. In an example, the neutral diacyl lipid comprises glyceryl dioleate (GDO).

[0039] In an example, component b) of the composition contains phosphatidylcholine. In an example, the phospholipid contains soybean phosphatidylcholine.

[0040] In the examples, component c) of the composition comprises ethanol. In the examples, the ethanol is provided in a sufficiently large amount to provide solubility of at least 10 mg / g, 20 mg / g, or 30 mg / g of cermelan peptide.

[0041] In an embodiment, component d) of the composition comprises a polar solvent, such as a buffer solution, for example, a citrate buffer, optionally wherein the pH of the buffer solution is 6.4. In an embodiment, the polar solvent, such as the buffer solution, comprises citrate monohydrate. In an embodiment, the polar solvent, such as the buffer solution, comprises additional components, such as an antioxidant or a chemical or physical stabilizer. In an embodiment, the antioxidant is EDTA. In an embodiment, the polar solvent, such as the buffer solution, comprises citrate monohydrate, disodium EDTA, and water.

[0042] In this embodiment, component e) is a semelan peptide. In this embodiment, component e) is MC4RA. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0043] In the embodiments, component e) provides cermelan peptide as the sole active ingredient.

[0044] In the embodiments, component e) provides cermelan peptide as an active pharmaceutical ingredient.

[0045] In the embodiments, component e) provides cermelan peptide as an active pharmaceutical ingredient for injection.

[0046] In the embodiments, component e) provides MC4RA as the sole active ingredient. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0047] In the embodiment, component e) provides MC4RA as the sole active ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0048] In the embodiments, component e) provides MC4RA as an active pharmaceutical ingredient. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0049] In the embodiment, component e) provides MC4RA as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0050] In one embodiment, the injectable pharmaceutical product comprises ceramide peptide as the active pharmaceutical ingredient. In another embodiment, the injectable pharmaceutical product comprises: a neutral diacyl lipid containing dioleoglyceride; a phospholipid containing phosphatidylcholine; an alcohol containing ethanol; a polar solvent, such as a buffer solution containing, for example, a citrate buffer containing EDTA at pH 6.4; and ceramide peptide.

[0051] In an example, the injectable drug product comprises, per milliliter of composition, 419.8 mg of glyceryl dioleate (GDO); 419.8 mg of soybean phosphatidylcholine; 105 mg of ethanol; 20 mg of citrate buffer; and 30 mg of ceramide peptide.

[0052] On the other hand, this disclosure provides a method for manufacturing a formulation or composition, such as a pharmaceutical composition, for example a formulation or composition having a controlled level of EtOH, the formulation or composition comprising cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the method includes:

[0053] i) Provide cermelan peptide, or MC4RA, as the sole active pharmaceutical ingredient formulated for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), a first amount of EtOH and a mixture of one or more of the following components:

[0054] a) Neutral diacyl lipids and / or tocopherols;

[0055] b) Phospholipids;

[0056] c) alcohols; and

[0057] d) Polar solvents, such as buffer solutions; and

[0058] ii) Add a second amount of EtOH.

[0059] This allows for the manufacture of formulations or compositions, such as pharmaceutical compositions, that contain cermelan peptide; cermelan peptide as the sole active pharmaceutical ingredient formulated for injection; or MC4RA. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0060] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0061] In an embodiment, the method further includes manufacturing a mixture comprising: ceramide peptide; ceramide peptide as the sole active pharmaceutical ingredient formulated for injection; ceramide peptide as the sole active ingredient; ceramide peptide as an active pharmaceutical ingredient; ceramide peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); EtOH, neutral diacid lipids and / or tocopherols and phospholipids,

[0062] This includes cymelan peptide, which is the sole active pharmaceutical ingredient in a formulation for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11), and after being combined with EtOH, one or two of neutral diacyl lipids and / or tocopherols, and phospholipids are added;

[0063] This allows for the manufacture of compositions or formulations, such as pharmaceutical products, having the following components: cymelanide; cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0064] In another aspect, a method of manufacturing a pharmaceutical product comprising: cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); component a; component b; component d; and a predetermined amount of alcohol, the method comprising:

[0065] MC4RA is a drug that is formulated as the sole active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); Component a, component b, component d, and alcohol (in any order) are combined to provide a mixture, and

[0066] The alcohol content value in the mixture was compared with a reference value for alcohol content.

[0067] This allows for the manufacture of formulations containing: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient in a formulation for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11), component a, component b, component d and a predetermined amount of alcohol.

[0068] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0069] In one embodiment, the method further includes increasing or decreasing the amount of alcohol in the mixture in response to the value or comparison to provide a formulation having a predetermined amount of alcohol. In another embodiment, the method includes adding an additional amount of alcohol to the mixture.

[0070] On the other hand, a method for manufacturing a pharmaceutical product comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer solution, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, the method comprising:

[0071] Combined (in any order) cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4) and an alcohol, to provide a mixture, and

[0072] The alcohol content value in the mixture was compared with a reference value for alcohol content.

[0073] This manufactures a pharmaceutical product comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol.

[0074] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0075] In one embodiment, the method further includes adding an additional amount of alcohol to the mixture. In another embodiment, the added amount of alcohol is greater than the predetermined amount of alcohol.

[0076] In one aspect, a method for manufacturing a pharmaceutical product comprising component e), wherein component e) comprises cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the method includes:

[0077] (i) Provides a mixture (component e) and an alcohol, wherein component e) comprises cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the mixture may contain, for example, cymelan peptide in contact with an alcohol such as ethanol, for example dissolved or dispersed in an alcohol such as ethanol, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); and

[0078] (ii) Combine the component e)-alcohol mixture with a certain amount of component a, such as GDO, component b, such as soybean PC, and component d, such as citrate buffer at pH 6.4, or all of components a, b and d.

[0079] In an embodiment, the method further includes performing steps (i), (ii), or (i) and (ii) in a sealed container.

[0080] In one aspect, this disclosure provides a method for manufacturing a formulation or evaluating a candidate formulation for, for example, quality control or release specification: cymelanide; cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the method includes:

[0081] Provide the value of the amount of EtOH in the candidate formulation of cymelanide; cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); and

[0082] Compare this value with a reference value for the amount of EtOH;

[0083] This leads to the manufacture of the following formulations: cymelanide; cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0084] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0085] In one aspect, this document provides a method for manufacturing a composition or formulation, such as a pharmaceutical product, having: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the method includes:

[0086] A mixture is prepared comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); EtOH, neutral diacid lipids and / or tocopherols and phospholipids,

[0087] This includes cymelan peptide, which is the sole active pharmaceutical ingredient in a formulation for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11), and after being combined with EtOH, one or two of neutral diacyl lipids and / or tocopherols, and phospholipids are added;

[0088] This allows for the manufacture of compositions or formulations, such as pharmaceutical products, having the following components: cymelanide; cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0089] In the embodiments, after allowing at least 10%, 25%, 50%, 75% or all of the following to enter the solution, one or two of neutral diacyl lipids and / or tocopherols, and phospholipids are added: cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0090] In this embodiment, the order of preparing the mixture is as follows:

[0091] i) MC4RA containing cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) are in contact with EtOH (and optionally water or buffer solution);

[0092] ii) Add phospholipids to the mixture obtained from i); and

[0093] iii) Add neutral diacyl lipids and / or tocopherols to the mixture obtained from ii).

[0094] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0095] On the other hand, a method for manufacturing a pharmaceutical product having component (e), said component (e) comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the method includes the following steps in sequence:

[0096] (i) Providing a mixture (component (e) - alcohol mixture) comprising cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as the active pharmaceutical ingredient, cymelan peptide as the active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as the active pharmaceutical ingredient, or as the active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), and an alcohol, the mixture comprising, for example, cymelan peptide in contact with, for example, ethanol, dissolved or dispersed in, an alcohol such as ethanol, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); and

[0097] (ii) Combine the component (e)-alcohol mixture with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC) and component d (e.g., citrate buffer at pH 6.4) or a certain amount of all of components a, b and d;

[0098] This leads to the manufacture of pharmaceutical products having the following characteristics: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P(e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), for example, a pharmaceutical product having the following and containing a predetermined amount of an alcohol, such as 10 wt.% of an alcohol, such as ethanol: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0099] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0100] In one aspect, a method for manufacturing a pharmaceutical product having component (e), said component (e) comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the method includes the following steps in sequence:

[0101] (i) Provide a mixture (component (e) - alcohol-buffer mixture) comprising: cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); alcohol; and component d (e.g., a polar solvent, such as a buffer solution, such as a citrate buffer at pH 6.4), the mixture comprising, for example, contact with an alcohol such as ethanol and a citrate buffer at pH 6.4, such as dissolving or dispersing in the alcohol such as ethanol and at pH 6.4. 6.4% citrate buffer, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); and

[0102] (ii) Combine component (e)-alcohol-buffer mixture with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC), or a certain amount of both components a and b;

[0103] Thus, a pharmaceutical product is manufactured having the following: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), for example, a pharmaceutical product having the following and containing a predetermined amount of an alcohol, such as 10 wt.% of ethanol: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0104] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0105] In another aspect, a method for manufacturing a pharmaceutical product comprising: ceramide peptide, component a, component b, component d, and a predetermined amount of alcohol, the method comprising...

[0106] In a specified order, ceramide peptide, component a, component b, component d, and an added amount of alcohol are combined, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, and wherein the specified order includes the following steps in sequence:

[0107] (i) Providing a mixture (a ceremonymide-alcohol mixture) comprising ceremonymide and an added amount of alcohol, such as ceremonymide contacted with an alcohol such as ethanol, for example dissolved or dispersed in an alcohol such as ethanol; and

[0108] (ii) Combine the ceramide peptide-alcohol mixture with a certain amount of components a, b and d or all of components a, b and d;

[0109] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising ceramide peptide, component a, component b, component d and a predetermined amount of alcohol, such as 10 wt.% alcohol, for example ethanol.

[0110] In another aspect, a method of manufacturing a pharmaceutical product, the pharmaceutical product comprising: component (e), the component (e) comprising cymelan peptide, cymelan peptide as a sole active pharmaceutical ingredient formulated for injection, cymelan peptide as a sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as a sole active ingredient, as a sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); component a (e.g., GDO); component b (e.g., soybean PC); component d (e.g., a polar solvent, such as a buffer solution, such as citrate buffer at pH 6.4); and a predetermined amount of alcohol, the method comprising...

[0111] In the specified order, the following are combined: component (e) containing cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); component a (e.g., GDO); component b (e.g., soybean PC); component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4); and an amount of alcohol added, wherein the amount of alcohol added results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order sequentially includes the following steps:

[0112] (i) Provides a mixture comprising component (e) and an added amount of alcohol (component (e)-alcohol mixture), wherein component (e) comprises cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the mixture may contain, for example, cymelan peptide in contact with an alcohol such as ethanol, for example dissolved or dispersed in an alcohol such as ethanol, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); and

[0113] (ii) Combining the component (e)-alcohol mixture with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC) and component d (e.g., citrate buffer at pH 6.4) or all of components a, b and d;

[0114] The pharmaceutical product comprising (i), (ii), or (i) and (ii) is manufactured in a closed vessel by means of: component (e), which comprises cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); component a (e.g., GDO); component b (e.g., soybean PC); component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4); and a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol.

[0115] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0116] On the other hand, a method for manufacturing a pharmaceutical product comprising semelan peptide, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol includes...

[0117] In a specified order, ceramide peptide, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and an added amount of alcohol are combined, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order includes the following steps in sequence:

[0118] (i) Providing a mixture (a ceremonymide-alcohol mixture) comprising ceremonymide and an added amount of alcohol, such as ceremonymide contacted with an alcohol such as ethanol, for example, dissolved or dispersed in an alcohol such as ethanol; and

[0119] (ii) The ceramide peptide-alcohol mixture is combined with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC) and component d (e.g., citrate buffer at pH 6.4) or all of components a, b and d;

[0120] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising ceramide peptide, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol.

[0121] In another aspect, a method of manufacturing a pharmaceutical product, the pharmaceutical product comprising: component (e), the component (e) comprising cymelan peptide, cymelan peptide as a sole active pharmaceutical ingredient formulated for injection, cymelan peptide as a sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as a sole active ingredient, as a sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); component a; component b; component d; and a predetermined amount of alcohol, the method comprising...

[0122] Combine the following in the specified order: component (e), that component (e) The product comprises cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RAP (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) as the sole active ingredient, the sole active ingredient for injection, the active pharmaceutical ingredient, or the active pharmaceutical ingredient for injection; component a; component b; component d; and an added amount of alcohol, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order includes the following steps in sequence:

[0123] (i) Provide a mixture (component (e) - buffer mixture) comprising: component (e), which contains cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as the active pharmaceutical ingredient, cymelan peptide as the active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as the active pharmaceutical ingredient, or as the active pharmaceutical ingredient for injection. P(e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); the amount of alcohol added; and component d (e.g., a polar solvent, such as a buffer solution, such as a citrate buffer at pH 6.4), the mixture containing, for example, contact with an alcohol such as ethanol and a citrate buffer at pH 6.4, such as dissolving or dispersing in the alcohol such as ethanol and at pH 6.4. 6.4% citrate buffer, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); and

[0124] (ii) Combine component (e)-alcohol-buffer mixture with a certain amount of components a and b or all of components a and b;

[0125] The pharmaceutical product comprising (i), (ii), or (i) and (ii) is manufactured in a closed vessel by means of: component (e), which comprises cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11); component a; component b; component d; and a predetermined amount of alcohol, e.g., 10 wt.% alcohol, e.g., ethanol.

[0126] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0127] In the embodiments, component e) provides cermelan peptide as the sole active ingredient.

[0128] In the embodiments, component e) provides cermelan peptide as an active pharmaceutical ingredient.

[0129] In the embodiments, component e) provides cermelan peptide as an active pharmaceutical ingredient for injection.

[0130] In the embodiments, component e) provides MC4RA as the sole active ingredient. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0131] In the embodiment, component e) provides MC4RA as the sole active ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0132] In the embodiments, component e) provides MC4RA as an active pharmaceutical ingredient. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0133] In the embodiment, component e) provides MC4RA as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0134] In one aspect, a method for manufacturing a pharmaceutical product comprising semelan peptide, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., citrate buffer at pH 6.4), and a predetermined amount of alcohol includes:

[0135] The ceramide peptide, component a, component b, component d, and an added amount of alcohol are combined in a specified order, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order includes the following steps in sequence:

[0136] (i) Provide a mixture (a ceremonymide-alcohol-buffer mixture) comprising ceremonymide, an added amount of alcohol, and component d, for example, a polar solvent, such as a buffer, such as a citrate buffer at pH 6.4, contacted with an alcohol, such as ethanol, and a citrate buffer at pH 6.4, for example, ceremonymide dissolved or dispersed in the alcohol, such as ethanol, and a citrate buffer at pH 6.4; and

[0137] (ii) Combine the cermelan peptide-alcohol-buffer mixture with a certain amount of components a and b or all of components a and b;

[0138] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising ceramide peptide, component a, component b, component d and a predetermined amount of alcohol, such as 10 wt.% alcohol, for example ethanol.

[0139] In another aspect, a method of manufacturing a pharmaceutical product, the pharmaceutical product comprising: component (e), the component (e) comprising cymelan peptide, cymelan peptide as a sole active pharmaceutical ingredient formulated for injection, cymelan peptide as a sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as a sole active ingredient, as a sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); component a (e.g., GDO); component b (e.g., soybean PC); component d (e.g., a polar solvent, such as a buffer solution, such as citrate buffer at pH 6.4); and a predetermined amount of alcohol, the method comprising...

[0140] In the specified order, the following are combined: component (e), which contains cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); component a; component b; component d; and an amount of alcohol added, wherein the amount of alcohol added results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order sequentially includes the following steps:

[0141] (i) Provide a mixture comprising component (e), an added amount of alcohol, and component d (e.g., a polar solvent, such as a buffer, such as a citrate buffer at pH 6.4) (component (e) - alcohol - buffer mixture), wherein component (e) Contains: cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as the active pharmaceutical ingredient, cymelan peptide as the active pharmaceutical ingredient for injection, or MC4RAP (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) as the sole active ingredient, as the sole active ingredient for injection, as the active pharmaceutical ingredient, or as the active pharmaceutical ingredient for injection. The mixture contains, for example, contact with an alcohol such as ethanol and a citrate buffer at pH 6.4, for example, dissolved or dispersed in an alcohol such as ethanol and at pH 6.4. The citrate buffer at 6.4 contains the following components (e): cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RAP (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection.

[0142] (ii) Combine component (e)-alcohol-buffer mixture with a certain amount of component a (e.g., GDO) and component b (e.g., soybean PC) or all of components a and b;

[0143] The pharmaceutical product comprising (i), (ii), or (i) and (ii) is manufactured in a closed vessel by means of: component (e), which comprises cymelan peptide, cymelan peptide as the sole active pharmaceutical ingredient formulated for injection, cymelan peptide as the sole active ingredient, cymelan peptide as an active pharmaceutical ingredient, cymelan peptide as an active pharmaceutical ingredient for injection, or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection.P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); component a (e.g., GDO); component b (e.g., soybean PC); component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4); and a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol.

[0144] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0145] In one aspect, a method for manufacturing a pharmaceutical product comprising semelan peptide, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol includes:

[0146] The ceramide peptide, component a, component b, component d, and an added amount of alcohol are combined in a specified order, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order includes the following steps in sequence:

[0147] (i) Provide a mixture (a ceremonymide-alcohol-buffer mixture) comprising the ceremonymide, an added amount of alcohol, and component d, for example, a polar solvent, such as a buffer, such as a citrate buffer at pH 6.4, contacted with an alcohol, such as ethanol, and a citrate buffer at pH 6.4, for example, ceremonymide dissolved or dispersed in an alcohol, such as ethanol, and a citrate buffer at pH 6.4; and

[0148] (ii) Combine the semmellan peptide-alcohol-buffer mixture with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC), or all of components a and b;

[0149] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising ceramide peptide, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol.

[0150] On the other hand, a method for manufacturing a pharmaceutical product comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the method includes the following steps in sequence:

[0151] i) Combining a certain amount of one or more (e.g., all) of components a, b, c, and d;

[0152] ii) Provide this mixture with cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); and

[0153] iii) Mixing the mixture of (i) and (ii) for a specified time to dissolve or disperse cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11),

[0154] This results in the manufacture of pharmaceutical products having the following characteristics: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), for example, a pharmaceutical product comprising the following and comprising a predetermined amount of an alcohol, such as 10 wt.% of an alcohol, such as ethanol: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0155] In one embodiment, the pharmaceutical product comprises secmelan peptide. In another embodiment, the mixture is subjected to a concentration of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 hours. In yet another embodiment, the mixture is subjected to a concentration of 1-30 hours. In yet another embodiment, the mixture is subjected to a concentration of no more than 30, 40, or 50 hours.

[0156] In one aspect, a method for manufacturing a pharmaceutical product comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the method includes the following steps in sequence:

[0157] i) Combining a certain amount of one or more (e.g., all) of components a, b, and d with the following: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11);

[0158] ii) To supply this mixture with a predetermined amount of component c; and

[0159] iii) Mixing the mixture of (i) and (ii) for a specified time to dissolve or disperse cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11),

[0160] Thus, a pharmaceutical product is manufactured having the following: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), for example, a pharmaceutical product comprising the following and containing a predetermined amount of an alcohol, such as 10 wt.% of ethanol: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0161] In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0162] In one embodiment, the mixing is carried out for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 hours. In another embodiment, the mixing is carried out for 1-30 hours. In yet another embodiment, the mixing is carried out for no more than 30, 40, or 50 hours.

[0163] On the other hand, this article discloses a method for providing subjects with: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the method includes administering to a subject an effective amount of the pharmaceutical product described herein or a pharmaceutical product manufactured by one or more of the methods described herein.

[0164] In this embodiment, the subject has a disorder that affects the regulation of melanocortin-4 receptor (MC4R) or is at risk of having such a disorder. In this embodiment, the disorder is selected from: type 1 diabetes, type 2 diabetes, obesity, insulin resistance, metabolic syndrome, erectile dysfunction in men, sexual dysfunction in women, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, substance abuse disorders including alcoholism, eating disorders, cachexia, inflammation, or anxiety. In this embodiment, the disorder is obesity. In this embodiment, the disorder is type 1 diabetes. In this embodiment, the disorder is type 2 diabetes. In this embodiment, the disorder is Prader-Willi syndrome. In this embodiment, the disorder is Bartholomew's syndrome. In this embodiment, the disorder is Alstrom syndrome.

[0165] In one embodiment, the subject was between 1 and 80 years old. In another embodiment, the subject was between 1 and 10 years old, 10 and 20 years old, 20 and 30 years old, 30 and 40 years old, 40 and 50 years old, 50 and 60 years old, 60 and 70 years old, or 70 and 80 years old. In yet another embodiment, the subject was over 80 years old.

[0166] In a related respect, this disclosure provides a method for treating a subject, the method comprising administering to the subject in need an effective amount of a composition comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0167] In this embodiment, the subject has a disorder that affects the regulation of melanocortin-4 receptor (MC4R) or is at risk of having such a disorder. In this embodiment, the disorder is selected from: type 1 diabetes, type 2 diabetes, obesity, insulin resistance, metabolic syndrome, erectile dysfunction in men, sexual dysfunction in women, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, substance abuse disorders including alcoholism, eating disorders, cachexia, inflammation, or anxiety. In this embodiment, the disorder is obesity. In this embodiment, the disorder is type 1 diabetes. In this embodiment, the disorder is type 2 diabetes. In this embodiment, the disorder is Prader-Willi syndrome. In this embodiment, the disorder is Bartholomew's syndrome. In this embodiment, the disorder is Alstrom syndrome.

[0168] In one embodiment, the subject was between 1 and 80 years old. In another embodiment, the subject was between 1 and 10 years old, 10 and 20 years old, 20 and 30 years old, 30 and 40 years old, 40 and 50 years old, 50 and 60 years old, 60 and 70 years old, or 70 and 80 years old. In yet another embodiment, the subject was over 80 years old.

[0169] In one aspect, this document provides compositions comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the composition is used to treat a subject in need, the use of which includes administering an effective amount of the composition to the subject.

[0170] In this embodiment, the subject has a disorder that affects the regulation of melanocortin-4 receptor (MC4R) or is at risk of having such a disorder. In this embodiment, the disorder is selected from: type 1 diabetes, type 2 diabetes, obesity, insulin resistance, metabolic syndrome, erectile dysfunction in men, sexual dysfunction in women, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, substance abuse disorders including alcoholism, eating disorders, cachexia, inflammation, or anxiety. In this embodiment, the disorder is obesity. In this embodiment, the disorder is type 1 diabetes. In this embodiment, the disorder is type 2 diabetes. In this embodiment, the disorder is Prader-Willi syndrome. In this embodiment, the disorder is Bartholomew's syndrome. In this embodiment, the disorder is Alstrom syndrome.

[0171] In one embodiment, the subject was between 1 and 80 years old. In another embodiment, the subject was between 1 and 10 years old, 10 and 20 years old, 20 and 30 years old, 30 and 40 years old, 40 and 50 years old, 50 and 60 years old, 60 and 70 years old, or 70 and 80 years old. In yet another embodiment, the subject was over 80 years old.

[0172] This document provides optimized pharmaceutical products comprising the following, as well as methods for manufacturing and using these optimized pharmaceutical products: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11. Typically, this pharmaceutical product contains neutral diglycerides and / or tocopherol, phosphatidylcholine, alcohol, a polar solvent (optionally containing an antioxidant), and cermelan peptide (or MC4RA disclosed herein). P In the embodiments, the pharmaceutical product has a low-viscosity phase, such as an L2 (reverse micelle) phase. The pharmaceutical products disclosed herein provide controlled release of: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0173] In this embodiment, the pharmaceutical product offers optimized release characteristics, is relatively easy to manufacture, can be aseptically filtered, has low viscosity at delivery (allowing for easy and less painful administration via, for example, fine needles, such as 27 gauge or smaller diameter needles), and allows for incorporation of high levels of: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) (Thus, in the embodiments, it is permissible to use smaller amounts of the composition and / or cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection.) P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11)) allowing for shallow injection (e.g., injection into the subcutaneous tissue layer) and / or formation of reservoirs (e.g., non-layered reservoirs) in vivo, such as reservoirs with a “non-burst release” characteristic. In the embodiments, the pharmaceutical product is formed from non-toxic, biotolerant, and biodegradable materials that can be administered via intramuscular (im) or subcutaneous (sc) administration and is suitable for self-administration. In the embodiments, the pharmaceutical product minimizes or eliminates irritation (including transient irritation) at the time of injection.

[0174] While not wishing to be bound by theory, it is assumed that in the embodiments, the pharmaceutical product produces a crystalline phase, such as a non-layered liquid crystalline phase, after administration.

[0175] In the embodiments, the pharmaceutical product provides the following low initial release (“non-burst release characteristic”): cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). This can be defined as the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 21, or 28 days), where the area under the drug concentration curve during the first few hours after dosing (e.g., the first 6, 9, 12, 15, 18, 21, or 24 hours) is less than 40% (e.g., less than 35%, 30%, 25%, 20%, 15%, 10%, or less). In this embodiment, the area under the drug concentration-time curve relative to a 7-day (e.g., 168-hour) steady-state dosing interval is less than 10% during the first 6 hours after administration. In this embodiment, the area under the drug concentration-time curve relative to a 7-day (e.g., 168-hour) steady-state dosing interval is 10%-20% (e.g., 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%) during the first 12 hours after administration. In this embodiment, the area under the drug concentration-time curve relative to a 7-day (e.g., 168-hour) steady-state dosing interval is 20%-30% (e.g., 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30%) during the first 24 hours after administration.

[0176] In the examples, following weekly injections of 5-20 mg doses (e.g., a 10 mg injection dose) every 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 days, the pharmaceutical product provided a mean maximum drug concentration (C0) in plasma ranging from 5-15 ng / mL at steady state. max(e.g., 11 ng / mL), this average maximum drug concentration is higher than the average drug concentration in the range of 1-8 ng / mL (C ave (e.g., 4 ng / mL) less than 3 times higher (1, 1.5, 2, or 2.5 times higher). In the examples, after a weekly 10 mg injection dose, the drug product provided a mean maximum drug concentration (C0) of 11 ng / mL in plasma at steady state. max The average maximum drug concentration was 4 ng / mL compared to the average drug concentration (C). ave (less than 3 times higher)

[0177] In the embodiments, at the time of administration, the minimum drug concentration in plasma under steady-state conditions (C) min The concentration is in the range of 1-3 ng / mL (e.g., 1.88 ng / mL). In the examples, the average cumulative index is in the range of 1-3 (e.g., 1.48), and the average fluctuation factor is in the range of 180%-210% (e.g., 199%). In the examples, cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) provide drug coverage within a one-week (e.g., 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14-day) dosing interval, as characterized in plasma under steady-state conditions.

[0178] In the embodiments, the cymelan peptide described herein; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) are optimized to allow the formulation of neutral diacid lipids and / or tocopherol and phospholipid components in a wide range of proportions. In the examples, the pharmaceutical products have a higher proportion of neutral diacid lipids and / or tocopherol to phospholipids compared to previously obtained products, with no risk of phase separation and / or no unacceptably high viscosity in the formulation. In the examples, the ratio of neutral diacyl lipids and / or tocopherols to phospholipids is 1:1, or a ratio between 0.5 and 1.0, 0.7 and 1.0, or 1 and 0.5 or 1 and 0.7.

[0179] The methods described herein allow for more precise and controlled levels of alcohol in formulations. Alcohol levels can affect release kinetics, such as burst-release characteristics. Too high a level can negatively impact release kinetics, such as burst-release characteristics. Therefore, controlling alcohol levels allows for more predictable and repeatable achievement of optimized release characteristics. Alcohol levels can also affect pre-injection viscosity; higher alcohol levels result in lower viscosity. Therefore, a defined and repeatable alcohol level allows for optimized performance. This document describes methods for incorporating the addition of known amounts of alcohol into steps to minimize or control evaporation loss levels. In examples, methods for manufacturing the pharmaceutical products described herein include using controlled amounts of alcohol to manufacture the pharmaceutical product. In examples, the pharmaceutical product is prepared, for instance, by using a sealed vessel (thereby reducing or controlling evaporation), thereby reducing or controlling evaporation. The use of a sealed vessel allows for precise control of the amount of alcohol used to manufacture the pharmaceutical product and can improve the reproducibility of the pharmaceutical product. Preventing evaporation loss is an important feature for reducing batch-to-batch variations and variations between individual dosage units within a batch of pharmaceutical products. Because this formulation can be used for in vivo delivery of ceremonymide; ceremonymide as the sole active pharmaceutical ingredient formulated for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), it is important that each batch of the drug product contains similar amounts of cymelan peptide at similar concentrations; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; or MC4RA P .

[0180] This article specifically discloses a specified order in which components are added to a formulation. This specified order can significantly affect the solubility of the components in the formulation, for example, the solubility of the following: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In an embodiment, a method of manufacturing the pharmaceutical product described herein includes adding components in a specified order to manufacture the pharmaceutical product. In an embodiment, cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4R-11 as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) after contacting with alcohol, cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) are contacted with one or more other components. This method can further optimize the time required to manufacture the formulation. A pharmaceutical product resulting from the sequential addition of components contains the following: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient; MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0181] In the embodiments, the control of alcohol content and the order of addition can be combined.

[0182] This disclosure contemplates all combinations of any one or more of the foregoing aspects and / or embodiments, as well as any one or more combinations of embodiments set forth in the detailed description and examples.

[0183] While similar or equivalent methods and materials may be used in the practice or testing of this invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references (e.g., sequence database reference numbers) mentioned herein are incorporated herein by reference in their entirety.

[0184] 1. An injectable composition or formulation, such as an injectable composition of a pharmaceutical product, comprising:

[0185] a) Neutral diacyl lipids and / or tocopherols;

[0186] b) Phospholipids:

[0187] c) Alcohols;

[0188] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0189] e) Semelan peptide, which is the only active pharmaceutical ingredient.

[0190] 2. The injectable composition as described in item 1, wherein the injectable composition comprises a neutral diacyl lipid.

[0191] 3. The injectable composition as described in item 4, wherein the neutral diacyl lipid comprises diglyceride.

[0192] 4. The injectable composition of claim 4, wherein the neutral diacyl lipid comprises glyceryl dioleate (GDO).

[0193] 5. The injectable composition of claim 1, wherein the phospholipid comprises phosphatidylcholine (e.g., soybean phosphatidylcholine).

[0194] 6. The injectable composition as described in item 1, wherein the alcohol comprises ethanol.

[0195] 7. The injectable composition of claim 6, wherein the ethanol is provided in a sufficiently large amount to provide solubility of at least 10 mg / g, 20 mg / g, or 30 mg / g of cermelan peptide.

[0196] 8. The injectable composition as described in item 6, wherein the amount of ethanol is greater than 1% by weight, for example, between 1 and 20% by weight.

[0197] 9. The injectable composition as described in item 6, wherein the amount of ethanol is low enough to allow a subject, such as the subject described herein, to easily and comfortably administer the injection using a device such as an syringe.

[0198] 10. The injectable composition of claim 6, wherein the amount of ethanol is less than 20%, 15% or 10% by weight.

[0199] 11. The injectable composition as described in item 6, wherein the amount of ethanol is large enough to give the composition a sufficiently low viscosity for comfortable delivery by means of a syringe, such as an syringe with a fine needle, such as a 27 gauge needle.

[0200] 12. The injectable composition of claim 6, wherein the amount of ethanol is sufficiently low to produce, for example, an initial burst release of the drug after subcutaneous injection, prior to administration of the next dose, of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2 or less) the maximum plasma concentration (C0). max ) and minimum concentration in plasma (C min The ratio of ).

[0201] 13. The injectable composition of claim 6, wherein the amount of ethanol is low enough to provide a low initial release of ceramide peptide after injection.

[0202] 14. The injectable composition of claim 13, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 6 hours) after dosing, the area being less than 10% or less.

[0203] 15. The injectable composition of claim 13, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 12 hours) after dosing, the area being less than 10%-20% or less.

[0204] 16. The injectable composition of claim 13, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 24 hours) after dosing, the area being less than 20%-30% or less.

[0205] 17. The injectable composition of claim 9, wherein the device may be a single-use device or a multiple-use device.

[0206] 18. The injectable composition of claim 9, wherein the device is selected from: a manual syringe (e.g., a syringe containing a needle (e.g., a needle of suitable diameter, such as a 27 gauge needle)) or an auto-injector (e.g., a spring-loaded syringe or a pen syringe).

[0207] 19. The injectable composition of claim 1, wherein the polar solvent, such as a buffer, comprises a citrate buffer, optionally wherein the pH of the buffer is 6.4.

[0208] 20. The injectable composition of claim 1, wherein the polar solvent, such as a buffer solution, comprises citrate monohydrate.

[0209] 21. The injectable composition of claim 1, wherein the polar solvent, such as a buffer solution, contains additional components, such as an antioxidant or a chemical or physical stabilizer.

[0210] 22. The injectable composition of claim 21, wherein the antioxidant is EDTA.

[0211] 23. The injectable composition of claim 1, wherein the polar solvent, such as a buffer solution, comprises citrate monohydrate, disodium EDTA, and water.

[0212] 24. The injectable composition as described in item 1, wherein the cermelan peptide is present as a chloride salt.

[0213] 25. The injectable composition of claim 1, wherein the pharmaceutical product optionally comprises an antimicrobial agent or a microbial inhibitor, such as an antibacterial agent or a preservative.

[0214] 26. The injectable composition as described in item 1, wherein the weight ratio of a:b is 70:30 to 40:60.

[0215] 27. The injectable composition as described in item 1, wherein the weight ratio of a:b is 70:30, 65:45, 60:40, 55:45, 50:50, 45:55 or 40:60.

[0216] 28. The injectable composition of claim 1, wherein component a is 20%-80%, 30%-70%, 33%-60%, or 38%-43% by weight of the total weight of the solutions of components a, b, and c.

[0217] 29. The injectable composition of claim 1, wherein component b is 20%-80%, 30%-70%, 33%-60%, or 38%-43% by weight of the total weight of the solutions of components a, b, and c.

[0218] 30. The injectable composition of claim 1, wherein component c, for example ethanol, is 0.5%-50%, 2%-30%, or 5%-20% by weight of the total weight of the solutions of components a, b, and c.

[0219] 31. The injectable composition as described in claim 1, wherein,

[0220] This neutral diacyl lipid contains dioleoyl glycerol ester;

[0221] This phospholipid contains phosphatidylcholine;

[0222] This alcohol contains ethanol; and

[0223] The polar solvent, such as a buffer solution, contains citrate buffer.

[0224] 32. The injectable composition as described in claim 1, wherein,

[0225] This neutral diacyl lipid contains dioleoyl glycerol ester;

[0226] This phospholipid contains soybean phosphatidylcholine;

[0227] This alcohol contains ethanol; and

[0228] The polar solvent, such as a buffer solution, contains citrate buffer at pH 6.4 containing EDTA.

[0229] 33. The injectable composition as described in claim 1, wherein each milliliter of the composition comprises:

[0230] 420 + / - 20% mg dioleoglycerate (GDO);

[0231] 420 + / - 20% mg soybean phosphatidylcholine;

[0232] 105 + / - 20% mg ethanol;

[0233] 20 + / - 20% mg citrate buffer; and

[0234] 30 + / - 20% mg ceramide peptide.

[0235] 34. The injectable composition as described in claim 1, wherein each milliliter of the composition comprises:

[0236] 420 + / - 10% mg dioleoglycerate (GDO);

[0237] 420 + / - 10% mg soybean phosphatidylcholine;

[0238] 105 + / - 10% mg ethanol;

[0239] 20 + / - 10% mg citrate buffer; and

[0240] 30 + / - 10% mg ceramide peptide.

[0241] 35. The injectable composition as described in claim 1, wherein each milliliter of the composition comprises:

[0242] 420 + / - 5% mg dioleoglycerate (GDO);

[0243] 420 + / - 5% mg soybean phosphatidylcholine;

[0244] 105 + / - 5% mg ethanol;

[0245] 20 + / - 5% mg citrate buffer; and

[0246] 30 + / - 5% mg cermelan peptide.

[0247] 36. The injectable composition as described in claim 1, wherein each milliliter of the composition comprises:

[0248] 420 + / - 2% mg dioleoglycerate (GDO);

[0249] 420 + / - 2% mg soybean phosphatidylcholine;

[0250] 105 + / - 2% mg ethanol;

[0251] 20 + / - 2% mg citrate buffer; and

[0252] 30 + / - 2% cermelan peptide.

[0253] 37. The injectable composition as described in claim 1, wherein each milliliter of the composition comprises

[0254] 419.8 mg dioleoylglycerol (GDO);

[0255] 419.8 mg soybean phosphatidylcholine;

[0256] 105 mg ethanol;

[0257] 20 mg citrate buffer; and

[0258] 30 mg cermelan peptide.

[0259] 38. The injectable composition of claim 1, wherein the injectable composition comprises:

[0260] The neutral diacyl lipid of component a, which, by weight, constitutes 20%-80%, 30%-70%, 33%-60%, or 38%-43% of components a, b, and c; components a, b, c, d, and e in the composition;

[0261] The phospholipid of component b, by weight, constitutes 20%-80%, 30%-70%, 33%-60%, or 38%-43% of components a, b, c, and d of the composition; or components a, b, c, d, and e.

[0262] The alcohol of component c, which, by weight, constitutes 0.1%-35%, 5%-20%, 8%-15%, or 9%-11% of components a, b, c, and d in the composition; or components a, b, c, d, and e.

[0263] The polar solvent of component d, such as a buffer solution, constitutes, by weight, 0.5%-10%, 1%-5%, or 1%-3% of components a, b, and c; components a, b, c, and d; or components a, b, c, d, and e; and

[0264] Semelan peptide, which, by weight, constitutes 0.1%-10%, 0.2%-8%, 0.5%-6%, and 1%-4% of components a, b, and c; components a, b, c, and d; or components a, b, c, d, and e in the composition.

[0265] 39. The injectable composition of claim 1, wherein the injectable composition comprises:

[0266] Neutral diacyl lipids, which, by weight, constitute 42% + / - 10, 42% + / - 5, 42% + / - 2, or 42% + / - 1 of components a, b, c, d, and e in the composition;

[0267] Phospholipids, by weight, comprising 42% + / - 10, 42% + / - 5, 42% + / - 2 or 42% + / - 1 of components a, b, c, d, and e in the composition;

[0268] An alcohol, by weight, comprising 10% + / - 8, 10% + / - 6, 10% + / - 5, or 10% + / - 1 of components a, b, c, d, or e in the composition;

[0269] A polar solvent, such as a buffer solution, comprising, by weight, 2% + / - 1, 2% + / - 0.5, 2% + / - 0.25, or 2% + / - 0.1% of components a, b, c, d, and e in the composition; and

[0270] Semelan peptide, which, by weight, constitutes 3% + / - 1.5, 3% + / - 1, or 3% + / - 0.5% of components a, b, c, and d, or components a, b, c, d, and e in the composition.

[0271] 40. The injectable composition of claim 1, wherein the injectable composition, upon contact with an aqueous environment, such as by injection, for example by subcutaneous injection into a subject, forms or is capable of forming at least one liquid crystalline structure.

[0272] 41. The injectable composition as described in item 1, wherein the viscosity is:

[0273] (i) low enough to be comfortably delivered by a device, such as a syringe with a fine needle, such as a 27-gauge needle;

[0274] (ii) low enough that, prior to administration of the next dose, secemerotide, after subcutaneous injection, produces a plasma concentration (C0.05) of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, or less) of the maximum plasma concentration (C0.05) following the initial burst release of the drug product. max ) and minimum concentration in plasma (C min The ratio of ); or

[0275] (iii) Low enough to provide a low initial release of ceramide peptide after injection.

[0276] 42. The injectable composition as described in claim 1, wherein when injected into a subject:

[0277] (i) Prior to administration of the next dose, secemerotide, following subcutaneous injection, produces a plasma maximum concentration (C0) of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2 or less) from the initial burst release of the drug product. max ) and minimum concentration in plasma (C min The ratio of ); or

[0278] (ii) The drug product provides low initial release of ceramide peptide.

[0279] 43. The injectable composition of claim 41, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 6 hours) after dosing, the area being less than 10% or less.

[0280] 44. The injectable composition of claim 41, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 12 hours) after dosing, the area being less than 10%-20% or less.

[0281] 45. The injectable composition of claim 41, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 24 hours) after dosing, the area being less than 20%-30% or less.

[0282] 46. ​​A unit dosage form comprising the composition as described in item 1.

[0283] 47. The unit dosage form as described in item 46, the unit dosage form comprising at least 2, 1.8, 1.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4 or 0.2 mL of the composition.

[0284] 48. The unit dosage form as described in item 46, wherein the unit dosage form is disposed in a liquid-tight casing, such as a vial or cartridge.

[0285] 49. The injectable unit dosage form as described in item 46, wherein the injectable unit dosage form is disposed in an injection device, such as a single-use device or a multiple-use device.

[0286] 50. The unit dosage form as described in item 49, wherein the device is selected from: a manual syringe (e.g., a syringe containing a needle (e.g., a needle of appropriate diameter, such as a 27 gauge needle)) or an auto-injector (e.g., a spring-loaded syringe or a pen syringe).

[0287] 51. The unit dosage form as described in item 46, the unit dosage form comprising 10-70; 20-60; 25-50; 25-40; 25-35 mg of cermelan peptide.

[0288] 52. The unit dosage form as described in item 46, comprising 50 + / - 20%; 40 + / - 20%; or 30 + / - 20% mg of cermelan peptide.

[0289] 53. The unit dosage form as described in item 46, comprising 50 + / - 10%; 40 + / - 10%; or 30 + / - 10% mg of cermelan peptide.

[0290] 54. The unit dosage form as described in item 46, comprising 50 + / - 5%; 40 + / - 5%; or 30 + / - 5% mg of cermelan peptide.

[0291] 55. The unit dosage form as described in item 46, comprising 40, 35, or 30 mg of cermelan peptide.

[0292] 56. The unit dose as described in item 46, wherein the composition is suitable for injection, such as subcutaneous or intramuscular injection.

[0293] 57. The unit dosage form as described in item 46, wherein the viscosity is:

[0294] (i) low enough to be comfortably delivered by a device, such as a syringe with a fine needle, such as a 27 gauge needle;

[0295] (ii) Low enough to produce a plasma maximum concentration (C0.05) of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2 or less) after the initial burst release of the drug product following subcutaneous injection before administration of the next dose. max ) and minimum concentration in plasma (C min The ratio of ); or

[0296] (iii) Low enough to provide a low initial release of ceramide peptide after injection.

[0297] 58. The unit dosage form as described in item 46, wherein when injected into a subject:

[0298] (i) Prior to administration of the next dose, the maximum plasma concentration (C0) of secmelanide following subcutaneous injection of the drug product, such as the initial burst release, is less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, or less). max ) and minimum concentration in plasma (C min The ratio of ); or

[0299] (ii) The drug product provides low initial release of ceramide peptide.

[0300] 59. The unit dosage form as described in item 46, wherein the low initial release is the area under the drug concentration-time curve relative to the 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 6 hours) after dosing, and the area is less than 10% or less.

[0301] 60. The unit dosage form as described in item 58, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 12 hours) after dosing, the area being less than 10%-20% or less.

[0302] 61. The unit dosage form as described in item 58, wherein the low initial release is the area under the drug concentration-time curve relative to the 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours after dosing (e.g., the first 24 hours), the area being less than 20%-30% or less.

[0303] 62. A method of manufacturing a formulation or composition, such as a pharmaceutical composition, for injection, comprising cermelan peptide as the sole active pharmaceutical ingredient, for example, a formulation or composition having a controlled level of EtOH, the method comprising:

[0304] i) Provide a mixture of ceramide peptide, a first amount of EtOH, and one or more of the following components:

[0305] a) Neutral diacyl lipids and / or tocopherols;

[0306] b) Phospholipids;

[0307] c) alcohols; and

[0308] d) Polar solvents, such as buffer solutions; and

[0309] ii) Add a second amount of EtOH.

[0310] This produces a formulation or composition, such as a pharmaceutical composition, which is formulated for injection and contains cermelan peptide as the sole active pharmaceutical ingredient.

[0311] 63. The method of claim 62, wherein providing includes forming the mixture.

[0312] 64. The method of claim 62, wherein the addition of the second amount of EtOH results in an amount of EtOH that satisfies a reference value, for example, falling within a range of values, for example, falling within a range defined by a lower limit and an upper limit, for example, the upper and lower limits of weight % EtOH, for example, 10-0.5 weight %.

[0313] 65. The method as described in item 64, wherein the reference value is a value in the range of 5 to 20; 8.5 to 12.5; and 9 to 11 wt% EtOH, for example, 10 wt%.

[0314] 66. The method as described in item 64, wherein the reference value is a value in the range of 9 to 11 wt% EtOH, for example 10 wt%.

[0315] 67. The method of claim 62, wherein the method comprises determining the amount of EtOH in the mixture by appropriate analytical determination.

[0316] 68. The method of claim 67, the method comprising, in response to the determination, selecting an amount of EtOH to be added to the mixture, for example, an amount to reach the reference value.

[0317] 69. The method of claim 68, the method comprising adding a selected amount of EtOH to the mixture to form an EtOH-replenished mixture.

[0318] 70. The method of claim 69, wherein the selected amount is added to the mixture as a single aliquot or as multiple aliquots of the same or different amounts.

[0319] 71. The method of claim 62, wherein less than 48 hours, less than 24 hours, or less than 4 hours have elapsed between the formation of the mixture and the determination of the amount of EtOH in the mixture, the selection of the amount of EtOH to be added, or the addition of the second amount.

[0320] 72. The method of claim 62, wherein the method includes providing the amount of the component to be added to the mixture.

[0321] 73. The method of claim 72, wherein providing includes weighing the amount of the component added to the mixture.

[0322] 74. The method of claim 62, the method comprising providing a value for the amount of EtOH in the mixture and determining the amount of EtOH to be added to satisfy a reference for the amount of EtOH.

[0323] 75. The method of claim 62, wherein after the mixture is formed, EtOH is lost from the mixture, for example by evaporation, such as evaporation into the top space of a container, such as a mixing vessel.

[0324] 76. The method of claim 62, wherein after the second amount is added to the mixture, the amount of EtOH in the EtOH-replenished mixture is determined.

[0325] 77. The method of claim 76, the method comprising, in response to the determination, selecting the amount of EtOH to be added to the mixture to which the EtOH is supplemented.

[0326] 78. The method of claim 77, wherein the method comprises adding a selected amount of EtOH to the EtOH-replenished mixture to form a mixture of two replenishments.

[0327] 79. The method of claim 62, further comprising providing a formulation or composition, such as a pharmaceutical product, for injection, comprising cermelan peptide as the sole active pharmaceutical ingredient.

[0328] 80. The method of claim 62, wherein the method comprises:

[0329] To manufacture a mixture comprising ceramide peptides, EtOH, neutral diacyl lipids and / or tocopherols and phospholipids.

[0330] After combining the ceramide peptide with EtOH, one or two of neutral diacyl lipids and / or tocopherols, and phospholipids are added.

[0331] This allows for the manufacture of cermelan peptide compositions or formulations, such as pharmaceutical products, that are prepared for injection.

[0332] 81. The method of item 62, wherein the method comprises:

[0333] To manufacture a mixture comprising ceramide peptide, water or a polar solvent such as a buffer, a neutral diacyl lipid and / or tocopherol and phospholipids,

[0334] After combining ceramide peptide with water or a polar solvent such as a buffer, one or both of neutral diacyl lipids and / or tocopherols, and phospholipids are added.

[0335] This allows for the manufacture of cermelan peptide compositions or formulations, such as pharmaceutical products, that are prepared for injection.

[0336] 82. The method as described in item 62, wherein the order of preparation of the mixture is:

[0337] i) Contact the ceramide peptide with EtOH (and optionally water or a polar solvent such as a buffer);

[0338] ii) Add the phospholipid to the mixture obtained from i); and

[0339] iii) Add the neutral diacyl lipid and / or tocopherol to the mixture obtained from ii).

[0340] 83. A method for manufacturing a pharmaceutical product formulated for injection, the pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient, component a, component b, component d, and a predetermined amount of alcohol, the method comprising:

[0341] Combine the ceramide peptide, component a, component b, component d, and alcohol (in any order) into a mixture, and

[0342] The alcohol content value in the mixture was compared with a reference value for alcohol content.

[0343] This produces a pharmaceutical product formulated for injection, comprising cermelan peptide as the sole active pharmaceutical ingredient, component a, component b, component d, and a predetermined amount of alcohol.

[0344] 84. The method of item 83, wherein the method comprises:

[0345] In response to this value or comparison, the amount of alcohol in the mixture is increased or decreased to provide a formulation with a predetermined amount of alcohol.

[0346] 85. The method of claim 83, wherein the method comprises adding an amount of alcohol to the mixture.

[0347] 86. The method of claim 85, wherein the amount of alcohol added is greater than the predetermined amount of alcohol.

[0348] 87. A method for manufacturing a pharmaceutical product formulated for injection, the pharmaceutical product comprising a cermelan peptide as the sole active pharmaceutical ingredient, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, the method comprising:

[0349] The ceramide peptide, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and alcohol (in any order) are combined into a mixture, and

[0350] The alcohol content value in the mixture was compared with a reference value for alcohol content.

[0351] This produces a pharmaceutical product formulated for injection, comprising cermelan peptide as the sole active pharmaceutical ingredient, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol.

[0352] 88. The method of claim 87, wherein the method comprises adding an amount of alcohol to the mixture.

[0353] 89. The method of claim 88, wherein the amount of alcohol added is greater than the predetermined amount of alcohol.

[0354] 90. The method of claim 87, wherein the predetermined amount is 5-20, 10-20, 15-20, 5-15, 5-10, 5-15 or 10-15 by weight.

[0355] 91. The method as described in item 87, wherein the predetermined amount is 10 + / - 5% by weight.

[0356] 92. The method as described in item 87, wherein the predetermined amount is 10 + / - 4 by weight.

[0357] 93. The method as described in item 87, wherein the predetermined amount is 10 + / - 3 by weight.

[0358] 94. The method as described in item 87, wherein the predetermined amount is 10 + / - 2 weight.

[0359] 95. The method as described in item 87, wherein the predetermined amount is 10 + / - 1 wt%.

[0360] 96. The method of item 87, wherein the predetermined amount is 10 + / - 0.5 by weight.

[0361] 97. The method of claim 87, wherein the method includes producing multiple batches of the preparation.

[0362] 98. The method of claim 97, wherein each of the plurality of batches has an alcohol content of 2, 1, or 0.5% by weight of one or more other batches in the plurality of batches.

[0363] 99. The method of claim 97, wherein each of the plurality of batches has an alcohol content within 2, 1 or 0.5% by weight of a reference value.

[0364] 100. The method as described in item 99, wherein the reference value is a value within the following range:

[0365] 5-20, 10-20, 15-20, 5-15, 5-10, 5-15 or 10-15% by weight;

[0366] 10 + / - 5% by weight%

[0367] 10 + / - 4% by weight;

[0368] 10 + / - 3% by weight;

[0369] 10 + / - 2% by weight;

[0370] 10 + / - 1% by weight; or

[0371] 10 + / - 0.5% by weight.

[0372] 101. The method of claim 99, wherein the reference value is a value in the range of 10 + / - 2 wt%, and each of the plurality of batches has an alcohol content in the range of 1 or 0.5 wt% of the reference value.

[0373] 102. The method of claim 99, wherein the reference value is 10% by weight, and each of the plurality of batches has an alcohol content within 0.5% by weight of the reference value.

[0374] 103. The method of claim 99, wherein each of the plurality of batches has a sufficiently high alcohol content to give the composition a sufficiently low viscosity for comfortable delivery by means of a device, such as an syringe with a fine needle, such as a 27-gauge needle.

[0375] 104. The method of claim 99, wherein each of the plurality of batches has a sufficiently low alcohol content to produce, for example, an initial burst release of ceramide peptide after subcutaneous injection, prior to administration of the next dose, results in a plasma concentration (C0) of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, or less) of the maximum concentration (C0) of ceramide peptide. max ) and minimum concentration in plasma (C min The ratio of ).

[0376] 105. The method of claim 99, wherein each of the plurality of batches has a sufficiently low alcohol content to provide a low initial release of ceramide peptide after injection.

[0377] 106. The method of claim 105, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 6 hours) after dosing, the area being less than 10% or less.

[0378] 107. The method of claim 105, wherein the low initial release is the area under the cermelanide concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 12 hours) after dosing, the area being less than 10%-20% or less.

[0379] 108. The method of claim 105, wherein the low initial release is the area under the cermelanide concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 24 hours) after dosing, the area being less than 20%-30% or less.

[0380] 109. The method of claim 103, wherein the device may be a single-use device or a multiple-use device.

[0381] 110. The method of claim 103, wherein the device is selected from: a manual syringe (e.g., a syringe containing a needle (e.g., a needle of suitable diameter, such as a 27 gauge needle)) or an auto-injector (e.g., a spring-loaded syringe or a pen syringe).

[0382] 111. The method of claim 87, wherein the predetermined amount of alcohol is added as a single aliquot sample.

[0383] 112. The method of claim 87, wherein the predetermined amount of alcohol is added as a plurality of aliquots.

[0384] 113. The method of claim 87, wherein at least a portion of the process following the addition of alcohol is carried out in a closed vessel.

[0385] 114. The method of claim 87, wherein the process following the addition of alcohol is carried out in a closed vessel.

[0386] 115. The method of claim 87, wherein at least a portion of the process prior to the addition of alcohol is carried out in a closed vessel.

[0387] 116. The method of claim 87, wherein the process prior to the addition of alcohol is carried out in a closed vessel.

[0388] 117. A method for manufacturing a pharmaceutical product formulated for injection, the pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient, the method comprising:

[0389] (i) Providing a mixture (a ceremonymide-alcohol mixture) comprising a ceremonymide and an alcohol, such as the ceremonymide being contacted with an alcohol such as ethanol, for example, dissolved or dispersed in an alcohol such as ethanol; and

[0390] (ii) Combine the ceramide peptide-alcohol mixture with a certain amount of components a, b and d, or all of components a, b and d.

[0391] 118. The method of claim 117, wherein steps (i), (ii), or (i) and (ii) are performed in a closed container.

[0392] 119. A method for manufacturing a pharmaceutical product formulated for injection, the pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient, the method comprising:

[0393] (i) Providing a mixture (a ceremonymide-alcohol mixture) comprising a ceremonymide and an alcohol, such as a ceremonymide contacted with an alcohol such as ethanol, such as a ceremonymide dissolved or dispersed in an alcohol such as ethanol; and

[0394] (ii) Combine the ceramide peptide-alcohol mixture with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC) and component d (e.g., citrate buffer at pH 6.4), or all of components a, b and d.

[0395] 120. The method of claim 119, wherein steps (i), (ii), or (i) and (ii) are performed in a closed container.

[0396] 121. A method for manufacturing cermelan peptide as a formulation of a single active pharmaceutical ingredient for injection or for evaluating candidate formulations for, for example, quality control or release specifications, the method comprising:

[0397] Provide values ​​for the amount of EtOH in the candidate formulation of ceremonymide; and

[0398] Compare this value with a reference value for the amount of EtOH;

[0399] This allows for the creation of a formulation of cermelan peptide as the sole active pharmaceutical ingredient for injection.

[0400] 122. The method of claim 121, further comprising selecting a candidate formulation of cermelanin in response to the comparison.

[0401] 123. The method of claim 121, wherein the reference value comprises a range defined by a lower limit and an upper limit, such as the upper and lower limits of weight % EtOH, for example, 10 wt%.

[0402] 124. The method as described in item 123, wherein satisfying the reference value includes falling within the range.

[0403] 125. The method as described in item 121, wherein the reference value is a value in the range of 5 to 20; 8.5 to 12.5; and 9 to 11 wt% EtOH, for example, 10 wt%.

[0404] 126. The method as described in item 125, wherein the reference value is a value in the range of 9 to 11 wt% EtOH, for example 10 wt%.

[0405] 127. The method of claim 121, the method comprising:

[0406] Provide the value of the amount of EtOH in a second candidate formulation of cermelan peptide as the sole active pharmaceutical ingredient for injection; and

[0407] Compare this value with a reference value for the amount of EtOH.

[0408] 128. The method of claim 121, the method comprising:

[0409] Provide the value of the amount of EtOH in N candidate formulations of ceremonymide as the sole active pharmaceutical ingredient to be formulated for injection, where N is equal to or greater than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, or 1,000; and

[0410] Compare this value with a reference value for the amount of EtOH.

[0411] 129. The method of claim 128, wherein the amount of EtOH in each of the plurality of formulations is within 5%, 2%, 1% or 0.5% of each other.

[0412] 130. The method of claim 128, wherein the amount of EtOH in each of the plurality of formulations is within 2% of each other.

[0413] 131. The method of claim 128, wherein the amount of EtOH in each of the plurality of formulations is within 0.5% of each other.

[0414] 132. The method of claim 128, wherein the first and second formulations of the plurality of formulations are manufactured within 10, 20, 30, 60, 180 or 365 days of each other.

[0415] 133. The method of claim 128, wherein the second formulation is manufactured less than 10, 20, 30, 60, 180, or 365 days after the first formulation.

[0416] 134. A method for manufacturing a composition or formulation comprising, for example, ceramide peptide as the sole active pharmaceutical ingredient, for injection, wherein the composition or formulation is a pharmaceutical product, the method comprising:

[0417] To manufacture a mixture comprising ceramide peptides, EtOH, neutral diacyl lipids and / or tocopherols and phospholipids.

[0418] After combining the component (e) containing ceramide peptide with the EtOH, one or both of neutral diacyl lipids and / or tocopherols, and phospholipids are added.

[0419] This allows for the manufacture of compositions or formulations containing cermelan peptide as the sole active pharmaceutical ingredient, such as pharmaceutical products, which are prepared for injection.

[0420] 135. The method of claim 134, wherein after at least 10, 25, 50, 75 or all of the ceramide peptide is allowed into the solution, one or both of neutral diacid lipids and / or tocopherols, and phospholipids are added.

[0421] 136. The method as described in item 134, wherein the order of preparation of the mixture is:

[0422] i) Contact the ceramide peptide with EtOH (and optionally water or buffer);

[0423] ii) Add phospholipids to the mixture obtained from i); and

[0424] iii) Add neutral diacyl lipids and / or tocopherols to the mixture obtained from ii).

[0425] 137. A method for manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, the method comprising the following steps in sequence:

[0426] (i) Providing a mixture (a ceremonymide-alcohol mixture) comprising a ceremonymide and an alcohol, such as a ceremonymide contacted with an alcohol such as ethanol, such as a ceremonymide dissolved or dispersed in an alcohol such as ethanol; and

[0427] (ii) Combine the cermelan peptide-alcohol mixture with a certain amount of one or more of components a, b and d;

[0428] This allows for the manufacture of pharmaceutical products containing cermelan peptide as the sole active pharmaceutical ingredient in a formulation for injection, such as a drug containing a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol, and containing cermelan peptide as the sole active pharmaceutical ingredient.

[0429] 138. A method for manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, the method comprising the following steps in sequence:

[0430] (i) Providing a mixture comprising a semelan peptide and an alcohol, such as a semelan peptide that has been contacted with an alcohol such as ethanol, for example dissolved or dispersed in an alcohol such as ethanol; and

[0431] (ii) Combine the mixture with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC) and component d (e.g., citrate buffer at pH 6.4) or a certain amount of all of components a, b and d;

[0432] This allows for the manufacture of a pharmaceutical product containing cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, for example, a pharmaceutical product containing a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol, and containing cermelan peptide as the sole active pharmaceutical ingredient formulated for injection.

[0433] 139. A method for manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, the method comprising the following steps in sequence:

[0434] (i) Providing a mixture comprising ceremonitrile peptide, an alcohol, and a component d, for example, a polar solvent such as a buffer, contacted with an alcohol such as ethanol, and the buffer, for example, ceremonitrile peptide dissolved or dispersed in an alcohol such as ethanol, and the buffer; and

[0435] (ii) Combine the mixture with a certain amount of one or more of components a and b;

[0436] This allows for the manufacture of a pharmaceutical product containing cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, for example, a pharmaceutical product containing a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol, and containing cermelan peptide as the sole active pharmaceutical ingredient formulated for injection.

[0437] 140. A method for manufacturing a pharmaceutical product comprising semelan peptide as the sole active pharmaceutical ingredient formulated for injection, the method comprising the following steps in sequence:

[0438] (i) A mixture is provided comprising a ceramide peptide, an alcohol, and a component d, for example, a polar solvent, such as a buffer, such as a citrate buffer at pH 6.4, comprising a ceramide peptide contacted with an alcohol, such as ethanol, and a citrate buffer at pH 6.4, for example, dissolved or dispersed in an alcohol, such as ethanol, and a citrate buffer at pH 6.4; and

[0439] (ii) Combine the mixture with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC), or a certain amount of both components a and b;

[0440] This allows for the manufacture of pharmaceutical products containing cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, such as pharmaceutical products containing a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol, and using cermelan peptide as the sole active pharmaceutical ingredient formulated for injection.

[0441] 141. A method of manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a, component b, component d, and a predetermined amount of alcohol, the method comprising:

[0442] In a specified order, ceramide peptide, component a, component b, component d, and an added amount of alcohol are combined, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, and wherein the specified order includes the following steps in sequence:

[0443] (i) Providing a mixture comprising semelan peptide and an added amount of alcohol, such as semelan peptide contacted with an alcohol such as ethanol, for example dissolved or dispersed in an alcohol such as ethanol; and

[0444] (ii) Combine the mixture with a certain amount of components a, b and d or all of components a, b and d;

[0445] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a, component b, component d, and a predetermined amount of alcohol, such as 10 wt.% alcohol, for example ethanol.

[0446] 142. A method of manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a, component b, component d, and a predetermined amount of alcohol, the method comprising:

[0447] In a specified order, ceramide peptide, component a, component b, component d, and an added amount of alcohol are combined, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, and wherein the specified order includes the following steps in sequence:

[0448] (i) Providing a mixture (a ceremonymide-alcohol mixture) comprising ceremonymide and an added amount of alcohol, such as ceremonymide contacted with an alcohol such as ethanol, for example dissolved or dispersed in an alcohol such as ethanol; and

[0449] (ii) Combine the ceramide peptide-alcohol mixture with a certain amount of components a, b and d or all of components a, b and d;

[0450] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising ceramide peptide, component a, component b, component d and a predetermined amount of alcohol, such as 10 wt.% alcohol, for example ethanol.

[0451] 143. A method of manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, the method comprising...

[0452] In a specified order, ceramide peptide, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and an added amount of alcohol are combined, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order includes the following steps in sequence:

[0453] (i) Providing a mixture comprising semelan peptide and an added amount of alcohol, such as semelan peptide contacted with an alcohol such as ethanol, for example dissolved or dispersed in an alcohol such as ethanol; and

[0454] (ii) Combine the mixture with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC) and component d (e.g., citrate buffer at pH 6.4) or all of components a, b and d;

[0455] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising ceramide peptide as the sole active pharmaceutical ingredient formulated for injection, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol.

[0456] 144. A method of manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, the method comprising...

[0457] In a specified order, ceramide peptide, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and an added amount of alcohol are combined, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order includes the following steps in sequence:

[0458] (i) Providing a mixture (a ceremonymide-alcohol mixture) comprising ceremonymide and an added amount of alcohol, such as ceremonymide contacted with an alcohol such as ethanol, for example, dissolved or dispersed in an alcohol such as ethanol; and

[0459] (ii) The ceramide peptide-alcohol mixture is combined with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC) and component d (e.g., citrate buffer at pH 6.4) or all of components a, b and d;

[0460] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising ceramide peptide, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol.

[0461] 145. A method of manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a, component b, component d, and a predetermined amount of alcohol, the method comprising:

[0462] In a specified order, ceramide peptide, component a, component b, component d, and an added amount of alcohol are combined, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order includes the following steps in sequence:

[0463] (i) A mixture is provided comprising ceramide peptide, an added amount of alcohol, and component d, for example, a polar solvent, such as a buffer, such as a citrate buffer at pH 6.4, contacted with an alcohol, such as ethanol, and a citrate buffer at pH 6.4, for example, ceramide peptide dissolved or dispersed in the alcohol, such as ethanol, and a citrate buffer at pH 6.4; and

[0464] (ii) Combine component (e)-alcohol-buffer mixture with a certain amount of components a and b or all of components a and b;

[0465] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a, component b, component d, and a predetermined amount of alcohol, such as 10 wt.% alcohol, for example ethanol.

[0466] 146. A method of manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a, component b, component d, and a predetermined amount of alcohol, the method comprising:

[0467] The ceramide peptide, component a, component b, component d, and an added amount of alcohol are combined in a specified order, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order includes the following steps in sequence:

[0468] (i) Provide a mixture (a ceremonymide-alcohol-buffer mixture) comprising ceremonymide, an added amount of alcohol, and component d, for example, a polar solvent, such as a buffer, such as a citrate buffer at pH 6.4, contacted with an alcohol, such as ethanol, and a citrate buffer at pH 6.4, for example, ceremonymide dissolved or dispersed in the alcohol, such as ethanol, and a citrate buffer at pH 6.4; and

[0469] (ii) Combine the cermelan peptide-alcohol-buffer mixture with a certain amount of components a and b or all of components a and b;

[0470] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a, component b, component d, and a predetermined amount of alcohol, such as 10 wt.% alcohol, for example ethanol.

[0471] 147. A method of manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, the method comprising...

[0472] In a specified order, ceramide peptide, component a, component b, component d, and an added amount of alcohol are combined, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order includes the following steps in sequence:

[0473] (i) A mixture is provided comprising ceramide peptide, an added amount of alcohol, and component d, for example, a polar solvent, such as a buffer, such as a citrate buffer at pH 6.4, contacted with an alcohol, such as ethanol, and a citrate buffer at pH 6.4, for example, ceramide peptide dissolved or dispersed in the alcohol, such as ethanol, and a citrate buffer at pH 6.4; and

[0474] (ii) Combine the mixture with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC), or all of components a and b;

[0475] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising ceramide peptide as the sole active pharmaceutical ingredient formulated for injection, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol.

[0476] 148. A method of manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, the method comprising...

[0477] The ceramide peptide, component a, component b, component d, and an added amount of alcohol are combined in a specified order, wherein the added amount of alcohol results in a predetermined amount of alcohol in the pharmaceutical product, wherein the specified order includes the following steps in sequence:

[0478] (i) Provide a mixture (a ceremonymide-alcohol-buffer mixture) comprising the ceremonymide, an added amount of alcohol, and component d, for example, a polar solvent, such as a buffer, such as a citrate buffer at pH 6.4, contacted with an alcohol, such as ethanol, and a citrate buffer at pH 6.4, for example, ceremonymide dissolved or dispersed in an alcohol, such as ethanol, and a citrate buffer at pH 6.4; and

[0479] (ii) Combine the semmellan peptide-alcohol-buffer mixture with a certain amount of component a (e.g., GDO), component b (e.g., soybean PC), or all of components a and b;

[0480] The pharmaceutical product is manufactured by performing (i), (ii), or (i) and (ii) in a closed vessel, comprising ceramide peptide as the sole active pharmaceutical ingredient formulated for injection, component a (e.g., GDO), component b (e.g., soybean PC), component d (e.g., a polar solvent, such as a buffer, such as citrate buffer at pH 6.4), and a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol.

[0481] 149. A method for manufacturing a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, the method comprising the following steps in sequence:

[0482] i) Combining a certain amount of one or more (e.g., all) of components a, b, c, and d;

[0483] ii) Provide this mixture with a component (e) containing ceramide peptide; and

[0484] iii) Mix the mixture of (i) and (ii) for a specified time to dissolve or disperse the ceramide peptide.

[0485] This allows for the manufacture of a pharmaceutical product in which cermelan peptide is the sole active pharmaceutical ingredient formulated for injection, for example, a pharmaceutical product containing a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol, and containing cermelan peptide as the sole active pharmaceutical ingredient formulated for injection.

[0486] 150. The method of claim 149, wherein the mixing is carried out for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 hours.

[0487] 151. The method as described in item 149, wherein the mixing is carried out for 1-30 hours.

[0488] 152. The method of claim 149, wherein the mixing is carried out for no more than 30, 40 or 50 hours.

[0489] 153. A method for manufacturing a pharmaceutical product comprising semelan peptide as the sole active pharmaceutical ingredient formulated for injection, the method comprising the following steps in sequence:

[0490] i) Combining a certain amount of one or more (e.g., all) of components a, b, and d with cermelan peptide;

[0491] ii) To supply this mixture with a predetermined amount of component c; and

[0492] iii) Mix the mixture of (i) and (ii) for a specified time to dissolve or disperse the ceramide peptide;

[0493] This allows for the manufacture of a pharmaceutical product containing cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, such as a pharmaceutical product containing a predetermined amount of alcohol, such as 10 wt.% alcohol, such as ethanol, and containing cermelan peptide as the sole active pharmaceutical ingredient formulated for injection.

[0494] 154. The method of claim 153, wherein the mixing is carried out for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 hours.

[0495] 155. The method as described in item 153, wherein the mixing is carried out for 1-30 hours.

[0496] 156. The method as described in item 153, wherein the mixing is carried out for no more than 30, 40 or 50 hours.

[0497] 157. A plurality of formulations of a pharmaceutical product comprising cermelan peptide as the sole active pharmaceutical ingredient formulated for injection, such as a first formulation, a second formulation, a third formulation or more, for example, a plurality of formulations manufactured by the method described in item 62, each of the plurality of formulations having a certain amount of EtOH falling within a predetermined range.

[0498] 158. The plurality of formulations as described in item 157, wherein the amount of EtOH in each of the plurality of formulations is within 2, 1 or 0.5% by weight of each other.

[0499] 159. The plurality of formulations as described in item 157, wherein the amount of EtOH in each of the plurality of formulations is in the range of 10 wt% + / - 5, 10 wt% + / - 4, 10 wt% + / - 3, 10 wt% + / - 2 or 10 wt% + / - 1.

[0500] 160. The plurality of formulations as described in item 157, wherein the first and second formulations of the plurality of formulations are manufactured within 10, 20, 30, 60, 180 or 365 days of each other.

[0501] 161. The various formulations as described in item 157, wherein a second formulation is manufactured in less than 10, 20, 30, 60, 180 or 365 days after the first formulation.

[0502] 162. A method of providing a subject with ceramide peptide as the sole active pharmaceutical ingredient formulated for injection, the method comprising administering to the subject an effective amount of the injectable composition as described in item 1.

[0503] 163. The method of claim 162, wherein the subject has a disorder that responds to the regulation of melanocortin-4 receptor (MC4R) or is at risk of having such a disorder.

[0504] 164. The method as described in item 163, wherein the disorder is selected from: type 1 diabetes, type 2 diabetes, obesity, insulin resistance, metabolic syndrome, erectile dysfunction in men, sexual dysfunction in women, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, substance abuse disorders including alcoholism, eating disorders, cachexia, inflammation or anxiety, Prad-Willi syndrome, Bartholomew's syndrome, and Alstrom syndrome.

[0505] 165. The method as described in item 164, wherein the obstacle is obesity.

[0506] 166. The method as described in item 164, wherein the disorder is type 1 diabetes.

[0507] 167. The method as described in item 164, wherein the disorder is type 2 diabetes.

[0508] 168. The method as described in item 164, wherein the disorder is Prader-Willi syndrome.

[0509] 169. The method as described in item 164, wherein the disorder is Bartholomew's syndrome.

[0510] 170. The method as described in item 164, wherein the disorder is Alstrom syndrome. Attached Figure Description

[0511] Figure 1A -B is a graph depicting the concentration-time characteristics of subcutaneous secemerophthalamide formulations 1A-1C (components of which are provided in Table 4), 5A-5C (components of which are provided in Table 2), and 3A / 4A (components of which are provided in Table 3); and SC infusion of secemerophthalamide. Figure 1A Concentration data with linear scaling were depicted, and Figure 1B Concentration data on a semi-logarithmic scale were depicted.

[0512] Figure 2A -B is a graph depicting the concentration-time characteristics of subcutaneous secemerophthalamide formulations 1D-1E (components of which are provided in Table 4) and 5D (components of which are provided in Table 2); and SC infusion of secemerophthalamide. Figure 2AConcentration data with linear scaling were depicted, and Figure 2B Concentration data on a semi-logarithmic scale were depicted.

[0513] Figure 3 The graph shows the average plasma concentration (ng / mL) of secemerophthalamide after a single subcutaneous dose (30 mg, 10 mg, or 2.5 mg) was administered to healthy subjects.

[0514] Figure 4 This is a graph depicting the trough concentration (ng / mL) of secemerophthalamide in the plasma of subjects after 4 weeks of continuous subcutaneous injection of a long-acting secemerophthalamide formulation administered multiple times a week.

[0515] Figure 5 This is a graph showing the percentage degradation of ceramide peptides in an exemplary formulation, wherein the GDO component is i) commercially pure GDO; ii) commercially pure GDO, further purified to remove fatty acid compounds; or iii) synthetic GDO.

[0516] Figure 6 This is a graph depicting the effect of EDTA concentration on the stability of an exemplary cermelan peptide formulation.

[0517] Figure 7 This is a graph depicting the effect of the concentration of ceremonymide in an exemplary ceremonymide formulation and its effect on degradation. Detailed Implementation

[0518] This disclosure provides at least a portion of a pharmaceutical product comprising: cymelanide (also known as RM493); cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or an MC4 receptor agonist (referred to as MC4RA) as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P Another pharmaceutical composition with the main mechanism of action of ), wherein the MC4 receptor agonist is, for example, BIM-22511 (also known as RM511), BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or the MC4 receptor agonist disclosed as SEQ ID NO: 11 in WO 2008 / 147556 (referred to as MC4R-11).

[0519] The pharmaceutical products disclosed herein produce a non-layered liquid crystalline phase upon administration. The use of non-layered phase structures (such as liquid crystalline phases) in the delivery of bioactive agents is known in the art. Exemplary lipid reservoir systems are described, for example, in WO 2005 / 117830, the entire contents of which are incorporated herein by reference.

[0520] Unless otherwise specified, all percentages are specified by weight throughout this document. Furthermore, the indicated weight percentages are % of the total pharmaceutical product comprising all components indicated herein. The pharmaceutical product may optionally consist substantially only of the components indicated herein (including, where appropriate, other optional components indicated herein and in the appended claims), and on the one hand, entirely of such components.

[0521] In this embodiment, the pharmaceutical product has an L2 phase structure. In this embodiment, the pharmaceutical product forms a non-layered (e.g., liquid crystal) phase upon administration.

[0522] In the embodiments, the pharmaceutical product allows for the peak concentration (C) of the drug in the plasma to be reached during the release period. max The concentration of C is controlled at a level equal to or less than that tolerated by the subject, for example to avoid side effects such as headache, changes in blood pressure, heart rate, respiratory rate, excessive sweating, or other adverse or undesirable effects, while providing or achieving an effective, for example, therapeutically effective level. Typically, the average concentration C during the release period before administering the next dose is [value missing]. ave Falling within the therapeutic range. To achieve effective and safe treatment over time, the maximum (C) dose is administered within a defined dosage period (e.g., once weekly or once monthly). max ) and minimum (C min Concentration control is also important. In one embodiment, the initial burst release is not a characteristic C-terminal release. max .

[0523] Regardless of whether the initial burst is still C max C max / C ave The ratios are all less than or equal to 10. In the embodiment, C ave / C min The ratio is less than or equal to 10, for example, less than or equal to 9, 8, 7, 6, 5, 4, 3, 2, or 1. In an embodiment, C ave / C min The ratio is less than 3. C max Defined as the peak or maximum plasma concentration observed during the release period prior to administration of the next dose, and C ave It is defined as the average plasma concentration during this release period. Accordingly, C minThis is the minimum concentration during this period. C can be calculated by taking the drug present in the plasma as the area under the curve (AUC) over the selected time period (typically the entire release period before administering the next dose) and dividing by that time period. ave .

[0524] Component (a) — Neutral diacyl lipids and / or tocopherols

[0525] As described herein, component "a" is a neutral lipid comprising a polar "head" group and a nonpolar "tail" group. Typically, the head and tail portions of the lipid are linked by an ester moiety, but this attachment can be achieved via ethers, amides, carbon-carbon bonds, or other attachments. In embodiments, the polar head group comprises a nonionic head group comprising a polyol (e.g., glycerol, diglycerol, or a sugar moiety (e.g., an inositol- or glucosyl-based moiety)) and an ester of the polyol (e.g., an acetate or succinate). In embodiments, the polar "head" group comprises glycerol or diglycerol.

[0526] In the embodiments, component (a) comprises a diacyl lipid having two nonpolar "tail" groups. The two nonpolar groups may have the same or different numbers of carbon atoms and may each be independently saturated or unsaturated. In the embodiments, the two nonpolar "tail" groups may have the same or different numbers of carbon atoms and may each be independently saturated or unsaturated. In the embodiments, the nonpolar groups include C6-C32 alkyl and alkenyl groups, which are generally present as esters of long-chain carboxylic acids. These are generally described by reference to the number of carbon atoms and the number of unsaturated bonds in the carbon chain. Thus, CX:Z indicates a hydrocarbon chain having X carbon atoms and Z unsaturated bonds.

[0527] In the embodiments, the nonpolar "tail" group of component (a) is selected from: lauroyl (C12:0), myristoyl (C14:0), palmitoyl (C16:0), phytanoyl (C16:0), palmitoleoyl (C16:1), stearoyl (C18:0), oleoyl (C18:1), transoleoyl (C18:1), linoleoyl (C18:2), linolenic acid (C18:3), arachidonic acid (C20:4), behenoyl (C22:0), or tetracosanoyl (C24:9). Typically, the nonpolar chain is based on fatty acids of natural ester lipids (including hexanoic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, phytanoic acid, palmitoleic acid, stearic acid, oleic acid, transoleic acid, linoleic acid, linolenic acid, arachidonic acid, behenic acid, or tetracosanoic acid) or the corresponding alcohol. In the embodiments, the nonpolar "tail" group of component (a) is selected from palmitic acid, stearic acid, oleic acid, or linoleic acid. In the embodiments, the nonpolar "tail" group of component (a) is oleic acid.

[0528] In the examples, component (a) The diacyl lipids are selected from: butyric acid (C4), valeric acid (C5), hexanoic acid (C6), heptanoic acid (C7), octanoic acid (C8), nonanoic acid (C9), decanoic acid (C10), undecanoic acid (C11), lauric acid (C12), tridecanoic acid (C13), myristic acid (C14), pentadecanoic acid (C15), palmitic acid (C16), heptadecanoic acid (C17), stearic acid (C18), nonadecanoic acid (C19), arachidic acid (C20), icosanoic acid (C21), benzyl acid (C22), tridecanoic acid (C23), tetradecanoic acid (C24), pentadecanoic acid (C25), hexadecanoic acid (C26), heptadecanoic acid (C27), octadecanoic acid (C28), nonadecanoic acid (C29), triacontanoic acid (C30), triacontanoic acid (C31), tridocoic acid (C32), tridecanoic acid (C33), and tridecanoic acid (C34). Alkane (C33), tetradecanoic acid (C34), pentadecanoic acid (C35), hexadecanoic acid (C36), heptadecanoic acid (C37), octadecanoic acid (C38), α-linolenic acid (18:3), linolenic acid (18:4), eicosapentaenoic acid (20:5), docosahexaenoic acid (22:6), linoleic acid (18:2), gamma-linolenic acid (18:3), di-homo-gamma-linolenic acid (20:3), arachidonic acid (20:4), docosahexaenoic acid (22:4), palmitoleic acid (16:1), isoleic acid (18:1), eicosenoic acid (20:1), oleic acid (18:1), trans-oleic acid (trans-18:1), squalinoic acid (20:1), erucic acid (22:1), nervonic acid (24:1), and medelic acid (20:3) or any pharmaceutically acceptable ester formed with an acid.

[0529] In the embodiments, a mixture of any number of diacyl lipids may be used as component (a). In the embodiments, component (a) comprises a portion of a C18 lipid (e.g., a diglyceride having one or more C18:0, C18:1, C18:2, or C18:3 nonpolar "tail" groups), such as glyceryl dioleate (GDO) or glyceryl dilinoleate (GDL).

[0530] In the embodiments, the diacyl lipid of component (a) comprises diacylglycerol (DAG), for example, dioleylglycerol (GDO). In the embodiments, the DAG of component (a) is GDO.

[0531] In an embodiment, component (a) is a DAG containing at least 50 wt.%, at least 80 wt.%, at least 90 wt.%, at least 95 wt.%, or 100 wt.% GDO. In an embodiment, component (a) contains 100 wt.% GDO.

[0532] In the embodiments, the diacyl lipids, when used in whole or in part as component (a), may be synthetic or may be derived from purified and / or chemically modified natural sources, such as plant oils. In the embodiments, the diacyl lipids (e.g., DAG, e.g., GDO) are synthetic. In the embodiments, the diacyl lipids (e.g., DAG, e.g., GDO) are derived from natural sources, such as plant or bacterial sources.

[0533] In some embodiments, the diacyllipid has a purity of at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.9% or higher. In some embodiments, the diacyllipid is GDO. In some embodiments, the GDO has a purity of at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.9% or higher. In some embodiments, the GDO has a purity of at least 50%. In some embodiments, the GDO has a purity of at least 75%. In some embodiments, the GDO has a purity of at least 85%. In some embodiments, the GDO has a purity of at least 90%. In some embodiments, GDO has a purity of at least 95%. In some embodiments, GDO has a purity of at least 98%. In some embodiments, GDO has a purity of at least 99%. In some embodiments, GDO has a purity between about 50% and 100%, about 75% to about 100%, or about 90% to 100%. In some embodiments, GDO has a purity between about 85% and 99%, about 88% and 96%, about 90% and 98%, about 90% and 96%, about 90% and 94%, about 90% and 92%, about 92% and 98%, about 92% and 96%, about 92% and 94%, about 94% and 98%, about 94% and 96%, about 96% and 98%, or 98% and 100%.

[0534] In embodiments, as described herein, GDO refers to any commercially grade GDO (commercially pure GDO) having accompanying impurities. Exemplary impurities include undesirable lipid and fatty acid compounds. These impurities can be separated and removed by purification. In embodiments, the GDO comprises chemically pure GDO, for example, GDO that is at least 80% pure, at least 85% pure, at least 90% pure, at least 95% pure, at least 99% pure, or 100% pure. In embodiments, the GDO contains less than about 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 2.5%, 1%, or 0.5% of impurities, such as undesirable lipid or fatty acid compounds. In embodiments, the GDO contains less than about 20% of impurities, such as undesirable lipid or fatty acid compounds. In embodiments, the GDO contains less than about 10% of impurities, such as undesirable lipid or fatty acid compounds. In embodiments, the GDO contains less than about 5% of impurities, such as undesirable lipid or fatty acid compounds. In one embodiment, the GDO contains less than about 2% impurities, such as undesirable lipid or fatty acid compounds. In another embodiment, the GDO contains less than about 1% impurities, such as undesirable lipid or fatty acid compounds.

[0535] In the embodiments, the undesirable lipid or fatty acid compounds are saturated lipids or unsaturated lipids. Exemplary undesirable lipid or fatty acid compounds include propionic acid, butyric acid, valeric acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, tridecanoic acid, myristic acid, palmitic acid, heptadecanoic acid, stearic acid, nonadecanoic acid, arachidic acid, icosanoic acid, benzanoic acid, trisaccharide, tetracosanoic acid, pentacosanoic acid, hexacosanoic acid, heptadecanoic acid, octacosanoic acid, nonadecanoic acid, triacontacosanoic acid, triacontacosanoic acid, triacontacosanoic acid, tritetracosanoic acid, tripentacontacosanoic acid, hexacosanoic acid, heptadecanoic acid, octacosanoic acid, myristoleic acid, palmitoleic acid, isoleic acid, cis-isooleic acid, eicosenoic acid, oleic acid, transoleic acid, 11-eicosenoic acid (i.e., stigmocarboxylic acid), erucic acid, brassidic acid, nervonic acid, and sapienic acid. (acid), codoleic acid, phellandrene, and linoleic acid (e.g., α-linolenic acid) or their isomers or variants.

[0536] In an embodiment, component (a) comprises tocopherol. In an embodiment, the tocopherol in component (a) comprises nonionic lipid tocopherol (e.g., vitamin E) or any suitable salt or analogue thereof. In an embodiment, suitable analogues of tocopherol comprise those that provide the following characteristics: phase behavior, non-toxicity, and phase change upon exposure to aqueous fluids.

[0537] In the embodiments, the tocopherol is purified from a natural source and may contain less than 10 wt.% of non-tocopherol "contaminants," for example, less than 10, 5, 4, 3, 2, 1 wt.% or less of contaminants. In the embodiments, component (a) contains at least 50, 80, 85, 90, 95, 99 wt.% or more of tocopherol (e.g., vitamin E) or any suitable salt or the like. In the embodiments, component (a) contains 100 wt.% of tocopherol (e.g., vitamin E) or any suitable salt or the like.

[0538] Component (b) -- Phosphatidylcholine

[0539] As described herein, component "b" comprises a phospholipid containing a polar head group and at least one nonpolar tail group. The nonpolar tail group may be derived from the fatty acid or corresponding alcohol described above for component a. In an embodiment, the phospholipid of component (b) contains two nonpolar tail groups. In one embodiment, the phospholipid of component (b) contains a C18 group and may be combined with any other suitable nonpolar tail group, particularly a C16 group. In one embodiment, the phospholipid of component (b) contains two identical nonpolar tail groups.

[0540] In the embodiments, the phospholipids of component (b) contain a polar head group selected from the following: phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, or phosphatidylinositol. In the embodiments, the polar head group of the phospholipids of component (b) is phosphatidylcholine (PC). In the embodiments, component (b) contains at least 50 wt.%, at least 70 wt.%, at least 80 wt.%, at least 90 wt.%, at least 95 wt.%, at least 99 wt.%, or 100 wt.% PC. In the embodiments, component (b) contains PC.

[0541] In embodiments, the PC of component (b) may be naturally derived, such as egg PC, heart PC (e.g., bovine heart PC), brain PC, liver PC (e.g., bovine brain PC or bovine liver PC), and plant-based (e.g., soybean PC). In embodiments, the naturally derived PC may comprise any mixture of phospholipids. In embodiments, the naturally derived PC comprises soybean PC or egg PC. In embodiments, the naturally derived PC comprises soybean PC. In embodiments, the PC comprises at least 50 wt.% soybean PC or egg PC, at least 75 wt.% soybean PC or egg PC, at least 80 wt.% soybean PC or egg PC, at least 90 wt.% soybean PC or egg PC, at least 95 wt.% soybean PC or egg PC, at least 99 wt.% soybean PC or egg PC, or 100 wt.% soybean PC or egg PC.

[0542] In the embodiments, the PC of component (b) is soybean PC. In the embodiments, the PC comprises 18:2 fatty acids as the major fatty acid component, and 16:0 and / or 18:1 as minor fatty acid components, wherein the ratio of the major to minor fatty acid components is between 1.5:1 and 6:1. In the embodiments, the PC of component (b) comprises 60%-65% 18:2, 10% to 20% 16:0, 5%-15% 18:1, with the remainder primarily consisting of other 16- and 18-carbon fatty acids. In the embodiments, the PC composed of soybean PC has the above composition.

[0543] In the examples, the PC of component (b) comprises synthetic dioleoyl PC. Synthetic dioleoyl PC is considered to provide increased stability and is therefore suitable for compositions requiring stability under long-term storage and / or having a long in vivo release period. In the examples, the PC of component (b) comprises at least 50 wt.%, at least 75 wt.%, at least 80 wt.%, at least 90 wt.%, at least 95 wt.%, at least 99 wt.%, or 100 wt.% of synthetic dioleoyl PC.

[0544] In some embodiments, the phospholipids of component (b) have a purity of at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.9% or higher. In some embodiments, the phospholipids of component (b) are phosphatidylcholine (PC). In some embodiments, PC has a purity of at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.9% or higher.

[0545] In the examples, component (b) contains synthetic or highly purified PC, such as dioleoylphosphatidylcholine (DOPC). In the examples, the synthesized dioleoyl PC includes 1,2-dioleoyl-sn-glycerol-3-phosphocholine and other synthetic PC components, such as DDPC (1,2-decanoyl-sn-glycerol-3-phosphocholine); DEPC (1,2-disorcinyl-sn-glycerol-3-phosphocholine); DLOPC (1,2-dilinoleoyl-sn-glycerol-3-phosphocholine); DLPC (1,2-dilauroyl-sn-glycerol-3-phosphocholine); DMPC (1,2-dimyristoyl-sn-glycerol-3-phosphocholine); DOPC (1,2-dioleoyl-sn-glycerol-3-phosphocholine); DPPC (1,2-dipalmitoyl-sn-glycerol-3-phosphocholine); DSPC (1,2-distearyl-sn-glycerol-3-phosphocholine). (1-Myristoyl-2-palmitoyl-sn-glycerol-3-phosphatecholine); MPPC (1-Myristoyl-2-stearoyl-sn-glycerol-3-phosphatecholine); MSPC (1-Myristoyl-2-stearoyl-sn-glycerol-3-phosphatecholine); PMPC (1-palmitoyl-2-myristoyl-sn-glycerol-3-phosphatecholine); POPC (1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphatecholine); PSPC (1-palmitoyl-2-stearoyl-sn-glycerol-3-phosphatecholine); SMPC (1-stearoyl-2-myristoyl-sn-glycerol-3-phosphatecholine); SOPC (1-stearoyl-2-oleoyl-sn-glycerol-3-phosphatecholine); and SPPC (1-stearoyl-2-palmitoyl-sn-glycerol-3-phosphatecholine) or any combination thereof.

[0546] In embodiments, component (b) comprising synthetic or highly purified PC (e.g., DOPC) can provide greater stability to the active agent in the formulation. In embodiments where the formulation does not contain an antioxidant, component (b) comprises (e.g., at least 75 wt.%) synthetic or highly purified (e.g., purity > 90%) PC (e.g., DOPC). In embodiments where the formulation contains an antioxidant, component (b) comprises (e.g., at least 75 wt.%) naturally derived PC, such as soybean PC or egg PC.

[0547] In one embodiment, the pharmaceutical product comprises a component (a) in the range of 20-80 wt.%, 30-70 wt.%, 33-60 wt.%, or 38-43 wt.%. In another embodiment, the pharmaceutical product comprises a component (b) in the range of 20-80 wt.%, 30-70 wt.%, 33-55 wt.%, or 38 to 43 wt.%.

[0548] In one embodiment, the pharmaceutical product comprises 42 wt.% of component (a). In another embodiment, the pharmaceutical product comprises 42 wt.% of component (a), wherein the neutral diacyl lipid is glyceryl dioleate (GDO).

[0549] In one embodiment, the pharmaceutical product comprises 42 wt.% of component (b). In another embodiment, the pharmaceutical product comprises 42 wt.% of component (b), wherein the phospholipid is phosphatidylcholine (PC). In another embodiment, the PC is soybean PC.

[0550] In one embodiment, the pharmaceutical product comprises at least 80, 70, 60, 50, 40, 30, or 20 wt.% of component (a). In another embodiment, the pharmaceutical product comprises at least 80, 70, 60, 50, 40, 30, or 20 wt.% of component (b). In yet another embodiment, the pharmaceutical product comprises at least 42% of component (a) (e.g., GDO) and at least 42% of component (b) (e.g., soybean PC).

[0551] In an embodiment, the pharmaceutical product comprises components (a) and (b), wherein component (a) (e.g., GDO) is present at 42 wt.% + / - 10, 42 wt.% + / - 5, 42 wt.% + / - 2, or 42 wt.% + / - 1.

[0552] In an embodiment, the pharmaceutical product comprises components (a) and (b), wherein component (b) (e.g., soybean PC) is present at 42 wt.% + / - 10, 42 wt.% + / - 5, 42 wt.% + / - 2, or 42 wt.% + / - 1.

[0553] In an embodiment, the pharmaceutical product comprises components (a) and (b), wherein component (a) (e.g., GDO) and component (b) (e.g., soybean PC) are each present at 42 wt.% + / - 10, 42 wt.% + / - 5, 42 wt.% + / - 2, or 42 wt.% + / - 1.

[0554] In the embodiments, the ratio of component (a):(b) is 40:60 to 70:30, 45:55 to 55:45, or 40:60 to 54:46. In the embodiments, the ratio of (a):(b) is 50:50.

[0555] In the embodiments, components (a) and (b) constitute 95 wt.%, for example, at least 95, 96, 97, 98, 99 wt.% or more of the lipid component in the pharmaceutical product. In the embodiments, components (a) and (b) constitute 99 wt.% of the lipid component in the pharmaceutical product. In the embodiments, the lipid component of the pharmaceutical product substantially comprises all, for example, 100 wt.% of components (a) and (b).

[0556] Component (c) -- alcohol

[0557] Component (c) as described herein comprises an alcohol. Since pharmaceutical products are typically used to create reservoir compositions after administration (e.g., in vivo) upon contact with excess aqueous fluid, it is desirable that the alcohol is tolerable to the subject and capable of mixing with and / or diffusing from the formulation or dissolving into the aqueous fluid. In the examples, component (c) comprises an alcohol having at least moderate water solubility.

[0558] In the embodiments, the alcohol of component (c) comprises ethanol, propanol, isopropanol, or a mixture thereof. In the embodiments, component (c) comprises ethanol.

[0559] In the embodiments, the addition or presence of less than 20 wt.% (e.g., less than 20, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3.5, 3, 2.5, 2, 1 wt.% or less) of an alcohol in the mixture comprising (a) and (b) resulted in a large viscosity reduction, such as a viscosity reduction of 30%-70%, for example, a reduction of 30%, 40%, 50%, 60%, or 70% or more. In the embodiments, the addition or presence of 10 wt.% of an alcohol in the mixture comprising (a) and (b) resulted in a viscosity reduction of 50%.

[0560] In the embodiments, the addition or presence of at least 10 wt.% alcohol to the mixture comprising (a) and (b) resulted in a viscosity reduction of at least 50% (e.g., at least 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%). In the embodiments, the addition or presence of at least 2.5 wt.% alcohol to the mixture comprising (a), (b), and at least 10 wt.% alcohol resulted in a further viscosity reduction of at least 50% (e.g., at least 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%). In the embodiments, the addition or presence of at least 3.5 wt.% alcohol to the mixture comprising (a), (b), and at least 12.5 wt.% alcohol resulted in a further viscosity reduction of at least 50% (e.g., at least 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%).

[0561] The amount of component (c) in a pharmaceutical product can have a significant impact on several characteristics. Specifically, viscosity and release rate (and duration) will vary with alcohol levels. Therefore, the amount of alcohol will be at least sufficient to provide a low-viscosity mixture that can be easily and comfortably injected by the patient applying manual pressure to the injection device, but the amount of alcohol will be determined separately to provide the release rate.

[0562] When administering a drug product using mechanical or other powered devices (such as devices that assist injection by applying a force greater than that applied manually, like auto-injectors), physical properties (such as viscosity) and reproducibility (such as batch-to-batch or injection-to-injection reproducibility) are important. When administering the drug product using such devices, such as auto-injectors, consistency of alcohol (such as ethanol) content within and between batches is important for reproducible performance, such as optimized pharmacokinetics.

[0563] Typically, alcohol levels of 0.1–35 wt.% or 5–20 wt.% will provide suitable release and viscosity characteristics. The amount of alcohol will also be sufficient to ensure the solubility of: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11). In an embodiment, the pharmaceutical product comprises a certain amount of component (c), such as ethanol, which is sufficient to provide a solubility of at least 10 mg / g, 20 mg / g, 30 mg / g, 40 mg / g, 50 mg / g or higher of the following: cymelanide; cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11). In an embodiment, the pharmaceutical product comprises a certain amount of component (c), such as ethanol, which is sufficient to provide a solubility of at least 30 mg / g for the following: ceremonymide; ceremonymide as the sole active pharmaceutical ingredient formulated for injection; ceremonymide as the sole active ingredient; ceremonymide as an active pharmaceutical ingredient; ceremonymide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0564] In the embodiments, the amount of component (c) in the pharmaceutical product is low enough that, upon injection and before administration of the next dose, the initial burst release of the drug after subcutaneous injection produces a plasma maximum concentration (C0) of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2 or less). max ) and minimum concentration in plasma (C minThe ratio of ).

[0565] In one embodiment, the pharmaceutical product comprises 0.1-35 wt.%, 5-20 wt.%, 8-15 wt.%, or 9-11 wt.% of component (c). In another embodiment, the pharmaceutical product comprises 20, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5 wt.% or less of component (c), wherein the alcohol of component (c) is ethanol. In yet another embodiment, the pharmaceutical product comprises 10 wt.% of component (c), wherein the alcohol of component (c) is ethanol.

[0566] The amount of component (c) in the pharmaceutical product described herein is sufficient to provide a low-viscosity mixture (e.g., a molecular solution) of components (a), (b), (c), and (d), and can be determined by standard methods for any particular combination of components.

[0567] In the embodiments, component (c) contains less than 5 wt.% (e.g., less than 5, 4, 3, 2, 1 wt.% or less) of halogenated hydrocarbons that have low biocompatibility.

[0568] Phase behavior can be analyzed using techniques such as a combination of visual observation and polarized light microscopy, X-ray scattering and diffraction, nuclear magnetic resonance, and cryo-transmission electron microscopy (cryo-TEM) to observe molecular solutions, L2 or L3 phases, or liquid crystalline phases, or dispersed fragments of such phases in the case of cryo-TEM. Viscosity can be measured directly using standard methods. In embodiments, a suitable practical viscosity is one that allows effective pressure to be applied to, for example, a device containing a pharmaceutical product (e.g., a syringe, such as a manual syringe (e.g., by manual pressure) or a spring-loaded syringe (e.g., an auto-injector)). In embodiments, a pharmaceutical product with a suitable practical viscosity allows pressure to be applied to a device (e.g., a syringe with an attached needle, such as one with a small-diameter needle suitable for injection (e.g., a 27-gauge needle)) to administer (e.g., release) the pharmaceutical product. In embodiments, a pharmaceutical product with a suitable practical viscosity can be sterilely filtered, for example, through a filter with a pore size of 0.2 micrometers or smaller.

[0569] In the embodiments, component (c) comprises a single alcohol or a mixture of alcohols (e.g., alcohols with low viscosity). In the embodiments, the formulations provided herein have low viscosity, and the primary role of a suitable solvent is to reduce this viscosity. This reduction will be attributed to a combination of the effects of the lower solvent viscosity and the molecular interactions between the solvent and the lipid composition. This document discloses the observation that the low-viscosity oxygenated solvents described herein have favorable molecular interactions with the lipid portion of the composition, thereby providing a non-linear reduction in viscosity with the addition of small volumes of solvent.

[0570] In the embodiments, the viscosity of the low-viscosity alcohol (single solvent or mixture) of component (c) is no greater than 18 mPas at 20ºC, for example, no greater than 15 mPas, 10 mPas or 7 mPas.

[0571] In one embodiment, the pharmaceutical product comprises components (a), (b), and (c), wherein component (a) is GDO, component (b) is soybean PC, and component (c) is ethanol. In another embodiment, the pharmaceutical product comprises 42 wt.% of component (a), 42 wt.% of component (b), and 10 wt.% of component (c), wherein component (a) is GDO, component (b) is soybean PC, and component (c) is ethanol.

[0572] Component (d) - Polar solvent or buffer

[0573] In the examples, combining alcohols with polar solvents (such as glycols or water or aqueous solutions, such as aqueous buffers, such as citrate buffers) allows for improved performance of lipid-based controlled-release compositions. It has been observed that the addition of glycols (e.g., propylene glycol) or water reduces the performance of the pharmaceutical product lipid / alcohol / cymenelan peptide; cymenelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymenelan peptide as the sole active ingredient; cymenelan peptide as an active pharmaceutical ingredient; cymenelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) viscosity without adversely affecting cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) release characteristics, and / or allow for an increase in the proportion of alcohol without adversely affecting the release characteristics and / or allow for an improvement in the release characteristics. When used herein, "adversely affects release characteristics" indicates C max / C ave The ratio increases and / or C max / C min The ratio increases, for example, by at least 1.2 times. Similarly, when used herein, "improved release characteristics" indicates C max / C ave and / or C max / C min The ratio decreases, for example, by at least 1.2 times.

[0574] In embodiments, the inclusion of a polar solvent (e.g., a polar solvent containing water) allows for improved control of the initial release and allows for higher stable loadings of: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In embodiments, infusions containing polar solvents (e.g., polar solvents containing water) provide faster reservoir formation and / or further relief of post-injection discomfort. Any of these factors provides a significant improvement in the context of therapeutic drug delivery, patient health, and / or patient compliance.

[0575] The component (d) described herein comprises a polar solvent that stabilizes the pH of the pharmaceutical product, for example, a solvent comprising water and optionally a pH-adjusting or buffering compound. In examples, the polar solvent of component (d) is selected from histidine buffer, citrate buffer, succinate buffer, acetate buffer, or phosphate buffer, or mixtures thereof. In examples, component (d) comprises citrate buffer, L-histidine buffer, or a mixture of L-histidine and L-histidine hydrochloride buffer. In examples, component (d) is citrate buffer.

[0576] In this embodiment, the citrate buffer of component (d) has a pH in the range of 5.8 to 7, for example, pH 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or 7.0. In this embodiment, the citrate buffer of component (d) has a pH of 6.4.

[0577] In one embodiment, the pharmaceutical product comprises at least 10 wt.% (e.g., showing 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5 wt.% or less) of component (d), wherein component (d) is a buffer, such as citrate buffer at pH 6.4. In another embodiment, the pharmaceutical product comprises component (d) in the range of 0.5-10 wt.%, 1-5 wt.%, or 1-3 wt.%, wherein component (d) is a buffer, such as citrate buffer at pH 6.4. In yet another embodiment, the pharmaceutical product comprises 2 wt.% of component (d), wherein component (d) is a buffer, such as citrate buffer at pH 6.4.

[0578] In the examples, the citrate buffer of component (d) comprises citrate monohydrate and optionally an antioxidant, such as disodium ethylenediaminetetraacetate (EDTA disodium salt). In the examples, component (d) comprises a solution of 30 mM citrate monohydrate. For example, 30 mM, 25 mM, 24 mM, 23 mM, 22 mM, 21 mM, 20 mM, 15 mM, 10 mM, or 5 mM citrate monohydrate. In the examples, component (d) comprises a solution of 23 mM citrate monohydrate.

[0579] In the examples, the citrate buffer of component (d) comprises citrate monohydrate and an antioxidant, for example, wherein the antioxidant is disodium ethylenediaminetetraacetate (EDTA). In the examples, component (d) comprises a solution of 30 mM citrate monohydrate (e.g., 30, 25, 24, 23, 22, 21, 20, 15, 10, or 5 mM citrate monohydrate) and a solution of 350 µM disodium ethylenediaminetetraacetate (e.g., 350, 340, 330, 320, 310, 300, 290, 280, 270, 260, 250, 200, 100, or 50 µM disodium ethylenediaminetetraacetate). In the examples, component (d) comprises a solution of 23 mM citrate monohydrate and a solution of 300 µM disodium ethylenediaminetetraacetate.

[0580] In the embodiments, component (d) comprises optional components, such as antioxidants or chemical or physical stabilizers selected from: EDTA (e.g., ethylenediaminetetraacetic acid, with pharmaceutically acceptable salts such as, but not limited to, sodium, calcium, and magnesium salts), BHA (butylated hydroxyanisole), BHT (butylated hydroxytoluene), ascorbic acid, α-tocopherol (vitamin E), or thiosulfate (with pharmaceutically acceptable salts such as, but not limited to, sodium or calcium salts).

[0581] In the embodiments, optional components of component (d), such as antioxidants or chemical or physical stabilizers, can stabilize and inhibit the oxidative degradation described herein of: ceremonylamide; ceremonylamide as the sole active pharmaceutical ingredient formulated for injection; ceremonylamide as the sole active ingredient; ceremonylamide as an active pharmaceutical ingredient; ceremonylamide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11. In the embodiments, optional components of component (d), such as antioxidants or chemical or physical stabilizers, do not reduce the solubility of: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection.) P(e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11); or without reducing the transparency of the pharmaceutical product, such as the transparency of the solution. In the examples, optional components of component (d), such as antioxidants or chemical or physical stabilizers, do not reduce the ability of the pharmaceutical product to form a structured gel-like structure after injection or contact with a simulated physiological fluid.

[0582] In the embodiments, the antioxidant in component (d) increases the physical and chemical stability of the following dissolved or dispersed components: ceremonylamide; ceremonylamide as the sole active pharmaceutical ingredient formulated for injection; ceremonylamide as the sole active ingredient; ceremonylamide as an active pharmaceutical ingredient; ceremonylamide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), resulting in a greater amount of cymelan peptide in the presence of antioxidants; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11). In the embodiments, in the lipid formulation, under normal storage conditions (e.g., 0-5ºC or 20ºC-25ºC), the antioxidant of component (d) increases the chemical and / or physical stability of: ceremonylamide; ceremonylamide as the sole active pharmaceutical ingredient formulated for injection; ceremonylamide as the sole active ingredient; ceremonylamide as an active pharmaceutical ingredient; ceremonylamide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0583] By including some polar solvents (especially water) that are miscible with the alcohol component, the slight sensation caused by the alcohol content at the injection site can be substantially eliminated. In the examples, the pharmaceutical product contains components (c):(d) in ratios between 10:90 to 90:10, 20:80 to 80:20, 30:70 to 70:30, or 40:60 to 60:40.

[0584] In an embodiment, the pharmaceutical product comprises components (c) and (d), wherein component (c) comprises ethanol (e.g., at least 20, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5 wt.% or less of ethanol), and component (d) comprises a citrate buffer optionally containing an antioxidant (e.g., at least 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5 wt.% or less of citrate buffer, optionally containing an antioxidant). In another embodiment, the formulation comprises 10% ethanol and 2% citrate buffer, wherein the buffer optionally contains an antioxidant.

[0585] In the embodiments, the pharmaceutical products described herein comprise GDO (e.g., 40-70 wt.% GDO), soybean PC (e.g., 40-70 wt.% GDO), ethanol (e.g., 5-20 wt.% ethanol), and a citrate buffer containing disodium ethylenediaminetetraacetate (e.g., 0.5-10 wt.% of a 23 mM citrate buffer containing 300 mM disodium ethylenediaminetetraacetate) or a mixture thereof. In the embodiments, the pharmaceutical product comprises 42 wt.% GDO, 42 wt.% soybean PC, 10 wt.% ethanol, 2 wt.% of a 23 mM citrate buffer containing 300 mM disodium ethylenediaminetetraacetate, or a mixture thereof.

[0586] Component (e)

[0587] As described herein, component (e) comprises cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In the examples, component e) comprises cermelan peptide.

[0588] In any of the embodiments described herein, component (e) comprises cymelanin peptide in a suitable salt or gel form; cymelanin peptide as the sole active pharmaceutical ingredient formulated for injection; cymelanin peptide as the sole active ingredient; cymelanin peptide as an active pharmaceutical ingredient; cymelanin peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In the examples, the salt form is a pharmaceutically acceptable salt. Exemplary salts (e.g., pharmaceutically acceptable salts) include acetates, benzenesulfonates, benzoates, bicarbonates, tartrates, bromides, calcium edetate, camphorsulfonates, carbonates, chlorides, citrates, dihydrochlorides, edetates, ethanedisulfonates, estolate, ethanesulfonates, fumarates, glyceptates, gluconates, glutamates, p-hydroxyacetaminophenarsine, and hexyl-m-hydroxyacetaminophenarsine. Hydroquinone salts, hydrobromides, hydrochlorides, hydroxynaphthylcarboxylate, iodides, hydroxyethanesulfonates, lactates, lacturonates, malates, maleates, mandelates, methanesulfonates, methyl sulfates, mucilages, naphthalenesulfonates, nitrates, pyrates, pantothenates, phosphates / bisphosphonates, polygalacturonates, salicylates, stearates, basic acetates, succinates, sulfates, tannates, tartrates, theochlorophosphates, toluenesulfonates, triethyliodide, and trifluoroacetates. In the examples, component (e) comprises semelan peptides in a suitable salt (e.g., a chloride salt). In an embodiment, component (e) comprises the following chloride salts: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In the examples, component (e) comprises a chloride salt of ceremonylamide.

[0589] In the embodiment, component (e) comprises MC4RA P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). Exemplary MC4RA models are described in Table 1. P The structure of the compound.

[0590] Table 1: MC4RA P Structure of compounds

[0591]

[0592] In the embodiment, component (e) comprises MC4RA P For example, the compound containing SEQ ID NO: 11 as described in International Application WO 2008 / 147556, the entire contents of which are hereby incorporated by reference. In the embodiments, the compound containing SEQ ID NO: 11 is referred to herein as MC4R-11.

[0593] In the embodiments, examples of compounds comprising SEQ ID NO: 11 (e.g., MC4R-11) include:

[0594] Cyclo[hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2;

[0595] Cyclic [hydantoin (C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2; or cyclic [hydantoin (C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2;

[0596] Or a pharmaceutically acceptable salt thereof, particularly cyclo[hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2.

[0597] In the examples, the compound comprising SEQ ID NO: 11, also known as MC4R-11, comprises the following amino acid sequence:

[0598] HXRWX (SEQ ID NO: 11), wherein X may be selected from: ornithine (Orn); 2,4-diaminobutyric acid (Dab); or 2,3-diaminopropionic acid (Dap).

[0599] In an embodiment, the pharmaceutical product comprises 0.02-12 wt.% cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In the examples, the pharmaceutical product comprises 0.02-12 wt.% cermelan peptide.

[0600] In an embodiment, the pharmaceutical product comprises 0.1-10 wt.%, 0.2-8 wt.%, 0.5-6 wt.%, and 1-4 wt.% of cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In the embodiments, the pharmaceutical product comprises 0.1-10 wt.%, 0.2-8 wt.%, 0.5-6 wt.%, and 1-4 wt.% of cermelan peptide.

[0601] In an embodiment, the pharmaceutical product comprises about 1 mg / mL, 2 mg / mL, 5 mg / mL, 10 mg / mL, 15 mg / mL, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, 75 mg / mL or more of cymelanide; cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0602] In one embodiment, the pharmaceutical product contains approximately 5 mg / mL of secemelelane. In another embodiment, the pharmaceutical product contains approximately 10 mg / mL of secemelelane. In another embodiment, the pharmaceutical product contains approximately 20 mg / mL of secemelelane. In another embodiment, the pharmaceutical product contains approximately 25 mg / mL of secemelelane. In another embodiment, the pharmaceutical product contains approximately 30 mg / mL of secemelelane. In another embodiment, the pharmaceutical product contains approximately 35 mg / mL of secemelelane. In another embodiment, the pharmaceutical product contains approximately 40 mg / mL of secemelelane.

[0603] In an embodiment, the pharmaceutical product comprises more than about 1 mg / mL, 2 mg / mL, 5 mg / mL, 10 mg / mL, 15 mg / mL, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, 75 mg / mL or more of cymelanide; cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0604] In an embodiment, the pharmaceutical product comprises less than about 50 mg / mL, 40 mg / mL, 35 mg / mL, 30 mg / mL, 25 mg / mL, 20 mg / mL, 15 mg / mL, 10 mg / mL, 5 mg / mL, 2 mg / mL, or 1 mg / mL of cymelanide; cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0605] In an embodiment, the pharmaceutical product comprises 3 wt.% ceremonylamide; ceremonylamide as the sole active pharmaceutical ingredient formulated for injection; ceremonylamide as the sole active ingredient; ceremonylamide as an active pharmaceutical ingredient; ceremonylamide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In this example, the pharmaceutical product comprises 3 wt.% cermelan peptide.

[0606] In the embodiments, 3 wt.% of cymelan peptide is included; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P Pharmaceutical products (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) are stable when stored at 25ºC for at least 1-6 months, for example, until... Less than 1, 2, 3, 4, 5, 6 months or longer, without the following loss or degradation: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In this example, the pharmaceutical product comprises 3 wt.% cermelan peptide.

[0607] In the embodiments, 3 wt.% of cymelan peptide is included; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. PPharmaceutical products, such as formulations, containing BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11, are stable at 5ºC for at least 1-6 months. For example, for at least 1, 2, 3, 4, 5, 6 months or longer, without the following loss or degradation: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In this example, the pharmaceutical product comprises 3 wt.% cermelan peptide.

[0608] In embodiments, about 1 mg / mL, 2 mg / mL, 5 mg / mL, 10 mg / mL, 15 mg / mL, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, 75 MC4RAP (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) products containing mg / mL or more of cymelanide; cymelanide as the sole active pharmaceutical ingredient (API) formulated for injection; cymelanide as the sole active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient; or MC4RAP products containing the sole active pharmaceutical ingredient, the sole active pharmaceutical ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection, and stored stably at 25ºC for at least 1–6 months. For example, for at least 1, 2, 3, 4, 5, 6 months or longer, without the following loss or degradation: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RAP as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11).

[0609] In embodiments, about 1 mg / mL, 2 mg / mL, 5 mg / mL, 10 mg / mL, 15 mg / mL, 20 mg / mL, 25 mg / mL, 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, 75 Cremylamine at a concentration of mg / mL or higher; Cremylamine as the sole active pharmaceutical ingredient formulated for injection; Cremylamine as the sole active ingredient; Cremylamine as an active pharmaceutical ingredient; Cremylamine as an active pharmaceutical ingredient; or MC4RAP (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) products that are stable at 5ºC for at least 1-6 months. For example, for at least 1, 2, 3, 4, 5, 6 months or longer, without the following loss or degradation: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RAP (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11) as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient or as an active pharmaceutical ingredient for injection.

[0610] In the embodiments, cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) In embodiments where the product is highly soluble in the alcohol of component (c), the following solubility in the alcohol is controlled: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0611] While not wishing to be bound by theory, it is believed that, in the embodiments, cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) Excessive dissolution of component (c) in the alcohol results in the alcohol transporting a significant amount of the following out of the reservoir composition in the event of formation in vivo: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In one embodiment, a polar solvent of the pharmaceutical product is used to control the solubility of the following in the pharmaceutical product: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), thereby helping to control the release characteristics. In an example, the pharmaceutical product comprises secmelan peptide.

[0612] In embodiments, this disclosure provides a method for controlling the solubility of the following in a low-viscosity mixture: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the low viscosity mixture comprises: (a) 40-70 wt.% of diglycerides and / or tocopherols; (b) 40-70 wt.% of phospholipids; (c) 5-20 wt.% of alcohols; (e) 1-4 wt.% of peptides; and (d) 0.5-10 wt.% of a polar solvent (optionally containing an antioxidant) to form a reservoir pharmaceutical product. In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0613] In embodiments, this disclosure provides a method for regulating the characteristics of the release of the following from a reservoir composition formed by injecting a low-viscosity mixture: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the low viscosity mixture comprises: (a) 40-70 wt.% of diglycerides and / or tocopherols; (b) 40-70 wt.% of phospholipids; (c) 5-20 wt.% of alcohols; (e) 1-4 wt.% of ceramide peptides; and (d) 0.5-10 wt.% of a polar solvent (optionally containing an antioxidant) in the low viscosity mixture to form a reservoir pharmaceutical product. In this embodiment, the pharmaceutical product comprises cermelan peptide.

[0614] In embodiments, this disclosure provides methods and uses for alleviating injection site discomfort, reducing the viscosity of a pharmaceutical product, and / or reducing the initial burst release of a low-viscosity mixture comprising: (a) 40-70 wt.% diglycerides and / or tocopherols; (b) 40-70 wt.% phospholipids; (c) 5-20 wt.% alcohols; (e) 1-4 wt.% ceremonylamide; and (d) 0.5-10 wt.% a polar solvent (optionally containing an antioxidant) in said low-viscosity mixture to form a reservoir of the pharmaceutical product. In an embodiment, the pharmaceutical product comprises ceremonylamide.

[0615] In the embodiments, this disclosure provides methods and uses for improving the properties of pharmaceutical products and / or resulting reservoir compositions without negatively impacting the following release characteristics: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In this embodiment, the pharmaceutical product comprises secmelan peptide.

[0616] Optional additional components

[0617] In the embodiments, the pharmaceutical products disclosed herein do not include (or include less than 5, 2, 1 or 0.5% by weight) fragmentation agents, such as polyethylene oxide or polyethylene glycol (PEG) fragmentation agents, for example, PEG-grafted lipids and / or surfactants.

[0618] In the embodiments, the pharmaceutical products disclosed herein do not include (or include less than 5, 2, 1 or 0.5% by weight) fragmentation agents such as polysorbate 80 (P80) or other polysorbates (e.g., polysorbate 20), PEGylated phospholipids (PEG-lipids such as DSPE-PEG(2000), DSPE-PEG(5000), DOPE-PEG(2000) and DOPE-PEG(5000)), Solutol HS 15, PEGylated fatty acids (e.g., PEG-oleate), block copolymers (e.g. Pluronic.RTM.F127 and Pluronic.RTM.F68), ethoxylated castor oil derivatives (e.g., Chremophores), PEGylated glycerol fatty acid esters (e.g., TMGO-15 from Nikko Chemicals), and PEGylated tocopherols (e.g., d-α-tocopherol poly(ethylene glycol) 1000 succinate, referred to as Vitamin E TPGS from Eastman).

[0619] In the embodiments, cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) are powders, for example, in the kit. In an example, the kit contains ceramide peptide.

[0620] In the embodiments, cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) are dissolved in lipid pharmaceutical products and their stability is increased by certain stabilizing additives. For example, storage stability and in vivo stability, these stabilizing additives are, for example, additives containing sugars (e.g., sucrose, trehalose, or lactose), polymers (e.g., polyols such as carboxymethyl cellulose), amino acids (e.g., methionine, glutamic acid, or lysine), lipid-soluble acid components (e.g., HCl), anionic lipids, or surfactants (e.g., dioleoyl phosphatidylglycerol (DOPG), palmitoyl oleoyl phosphatidylglycerol (POPG), or oleic acid (OA)). In some embodiments, the lipid pharmaceutical product comprises cermelan peptide.

[0621] In embodiments, the pharmaceutical products described herein comprise single-dose or multi-dose formulations. In embodiments, the single-dose or multi-dose formulations of the pharmaceutical product may be stored in pharmaceutically acceptable glass or plastic containers. In embodiments, the single-dose formulation of the pharmaceutical product remains stable, for example, chemically and physically stable, and is effective in storage before use, but can be discarded after a single use. In one embodiment, the single-dose or multi-dose formulation of the pharmaceutical product is stable at 4ºC, for example at 0ºC, 1ºC, 2ºC, 3ºC, or 4ºC, for at least 36 months, for example at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 25, 30, or 36 months. In embodiments, the single-dose or multi-dose pharmaceutical products are stable at 30ºC, for example at 20ºC, 21ºC, 22ºC, 23ºC, 24ºC, 25ºC, 26ºC, 27ºC, 28ºC, 29ºC, or 30ºC, for at least 36 months, for example at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 20, 25, 30, or 36 months. In embodiments, the multi-dose pharmaceutical products remain stable, for example, chemically and physically stable, and are effective before use, and remain stable (e.g., chemically and physically stable), effective, and relatively bacteria-free after the first use when the seal has been broken during the application period of the multi-dose regimen. In embodiments, the multi-dose pharmaceutical products contain antimicrobial agents or microbial inhibitors, such as antibacterial agents or preservatives.

[0622] In the embodiments, the pharmaceutical products described herein optionally comprise an antimicrobial agent or microbial inhibitor with sufficient antimicrobial activity, such as a bacteriostatic agent or preservative, to meet the standards of the European Pharmacopoeia (Ph. Eur.), the Japanese Pharmacopoeia (JP), and the United States Pharmacopeia (USP). In the embodiments, the bacteriostatic agent or preservative allows the pharmaceutical product to be stored and used in multiple doses. In the embodiments, the bacteriostatic agent or preservative does not reduce the solubility of the following: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), or reducing the transparency of the pharmaceutical product, such as the transparency of the solution. In the examples, the antibacterial agent or preservative contained in the pharmaceutical product is selected from phenol, benzoic acid, chlorobutanol, benzalkonium chloride, m-cresol, p-cresol, benzyl alcohol, or other phenolic preservatives. In the examples, the antibacterial agent or preservative is used at a concentration in which it is effective. In the examples, the antibacterial agent or preservative contained in the pharmaceutical product is pharmaceutically acceptable for administration by injection.

[0623] In the embodiments, the pharmaceutical products described herein may optionally contain antimicrobial agents or microbial inhibitors in addition to antioxidants or chemical or physical stabilizers (e.g., EDTA).

[0624] In the embodiments, the pharmaceutical products described herein comprising the following do not require additional preservatives, antimicrobial agents, or microbial inhibitors (e.g., bacteriostatic agents or bactericides) to provide multiple dosage forms: cymelanide; cymelanide as the sole active pharmaceutical ingredient formulated for injection; cymelanide as the sole active ingredient; cymelanide as an active pharmaceutical ingredient; cymelanide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In this embodiment, the pharmaceutical product comprises secmelan peptide.

[0625] In the embodiments, the pharmaceutical products described herein provide preservative effects and acceptable stability and pharmaceutical product stability for the following: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P(e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), and can be used for single-dose and multi-dose applications. In the examples, the pharmaceutical product comprises secmelan peptide.

[0626] In embodiments, the pharmaceutical products described herein in multipurpose forms comprise sufficient concentrations of ethanol and citrate buffer, alone or in combination (optionally containing sufficient concentrations of disodium EDTA), to provide preservative effects while maintaining the stability of: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), and pharmaceutical products. In an example, the pharmaceutical product comprises secmelan peptide.

[0627] Manufacturing Method - Specified Sequence

[0628] The following order of component combination in pharmaceutical products can optimize the manufacturing process: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), for example by reducing the time spent solubilizing the following: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In this embodiment, the pharmaceutical product comprises secmelan peptide.

[0629] In an embodiment, after contacting the following with an alcohol, for example, dissolving or dispersing them in an alcohol, a large portion, such as all, of components a, b, or both a and b are added: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In the embodiments, cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11) are dissolved or dispersed in alcohols such as ethanol. Once all or some of the following are included: cymelan peptides, for example, at least 50%, 70%, 80%, 90%, 95%, or 99%; cymelan peptides as the sole active pharmaceutical ingredient formulated for injection; cymelan peptides as the sole active ingredient; cymelan peptides as an active pharmaceutical ingredient; cymelan peptides as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) are dissolved or dispersed in ethanol, then a large portion, such as all, of components a, b, or both a and b are added to the mixture. In an example, cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) when dissolved or dispersed in alcohol, for example, when at least 50%, 70%, 80%, 90%, 95%, or 99% of cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) When dissolved or dispersed in ethanol, the mixture may also contain component d, such as a polar solvent, such as citrate buffer. In the examples, the pharmaceutical product comprises secmelan peptide.

[0630] In the embodiments, cymelan peptide is used as the sole active pharmaceutical ingredient in a formulation for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) are dissolved or dispersed in alcohol, thereby allowing cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) are contacted with one or more components a, b, and d. In an example, the pharmaceutical product comprises secmelan peptide.

[0631] Manufacturing method - controlling the amount of ethanol

[0632] It may be important to have a bioactive moiety (e.g., cymelan peptide) in a pharmaceutical product containing a predetermined or specified level (e.g., a level to optimize the viscosity of the pharmaceutical product before injection and the release characteristics after injection). Manufacturing methods may allow for uncontrollable or unpredictable levels of alcohol loss during manufacturing (e.g., through evaporation), and this loss can impair the ability to have controlled and reproducible levels of alcohol in the formulation. This document provides methods for manufacturing pharmaceutical products comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), this pharmaceutical product has controlled and reproducible levels of alcohols such as ethanol. The level of alcohol affects pre-delivery viscosity and post-delivery release characteristics. Alcohols generally promote lower viscosity, but if too much is present, it can have undesirable effects, for example, by increasing C0. max This affects the release characteristics. Therefore, controlled and reproducible alcohol levels are required.

[0633] The methods described herein control the alcohol level in a complete pharmaceutical product, such as a pharmaceutical product containing semelanide. Added alcohol lost through evaporation can cause variations in the alcohol level present in the pharmaceutical product. In embodiments, the method includes producing the pharmaceutical product by adding a controlled amount of ethanol in a closed system or vessel. Using a closed system or vessel minimizes alcohol loss due to evaporation.

[0634] In embodiments, this disclosure provides a method for manufacturing a pharmaceutical product described herein containing a controlled or predetermined amount of an alcohol, such as ethanol. In embodiments, the amount of alcohol, such as ethanol, in the pharmaceutical product is a predetermined amount, for example, 10%. The method of this disclosure includes adding a measured amount (sometimes referred to herein as the “addition amount”) of an alcohol, such as ethanol, which, under manufacturing conditions, results in a pharmaceutical product having a predetermined amount of alcohol, such as ethanol, after manufacturing. Typically, the addition amount will be greater than the predetermined amount present after manufacturing, for example, due to evaporation of the alcohol during manufacturing. In embodiments, the addition amount is added as a single aliquot, and in other embodiments, multiple aliquots are added to provide the addition amount. In embodiments, the method includes additional measures to reduce alcohol evaporation, such as performing one or more stages of the manufacturing process under conditions that reduce alcohol evaporation, for example, controlling the temperature or performing a stage of the process in a closed vessel.

[0635] In embodiments, alcohols, such as ethanol, may be provided to the pharmaceutical product in one or more amounts or aliquots, for example, in one, two, three, or four amounts or aliquots. In embodiments, a method of manufacturing a pharmaceutical product includes providing an alcohol, such as ethanol, in a first amount or aliquot to dissolve or disperse a peptide: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11). In an embodiment, a method of manufacturing a pharmaceutical product further includes providing a majority or all of components a, b, and d to a mixture dissolved or dispersed in ethanol: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In this embodiment, the pharmaceutical product comprises secmelan peptide.

[0636] In an embodiment, a method of manufacturing a pharmaceutical product further includes providing a next amount or aliquot of an alcohol, such as ethanol, to the mixture, for example, a second, third, or fourth amount or aliquot of the alcohol, thereby manufacturing a pharmaceutical product comprising 10 wt.% alcohol, such as ethanol, having the following: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0637] Treatment with compound preparations

[0638] The methods of applying the pharmaceutical products described herein are described in, for example, international applications WO 2013 / 102047, WO2014 / 144842 and WO 2017 / 059076, the entire contents of which are hereby incorporated by reference.

[0639] In the embodiments, MC4RA, as described in the text, comprises: cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) These pharmaceutical products are administered to subjects suffering from a disease or disorder that responds to the pharmaceutical activity of a peptide of a pharmaceutical product, such as: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In one embodiment, the pharmaceutical product comprises secmelan peptide.

[0640] In one embodiment, in a subject requiring treatment, the disorder to be treated responds to modulation of MC4R. The method includes administering to the subject an effective amount of a pharmaceutical product comprising an MC4R modulator as a peptide, such as cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4R as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). In this embodiment, the pharmaceutical product comprises secmelan peptide.

[0641] In the embodiments, disorders responsive to MC4R regulation include type 1 diabetes, type 2 diabetes, obesity, insulin resistance, metabolic syndrome, erectile dysfunction in men, sexual dysfunction in women, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, substance abuse disorders including alcoholism, eating disorders, cachexia, inflammation, and anxiety. In the embodiments, the disorder is obesity, type 1 diabetes, or type 2 diabetes. In the embodiments, the disorder is obesity or an obesity-related condition. In the embodiments, the disorder is Prader-Willi syndrome. In the embodiments, the disorder is Bartholomew's syndrome. In the embodiments, the disorder is Alstrom syndrome.

[0642] In embodiments, the disorder to be treated includes type 1 diabetes, type 2 diabetes, obesity, Prad-Willi syndrome, insulin resistance, metabolic syndrome, erectile dysfunction in men, sexual dysfunction in women, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, substance abuse disorders including alcoholism, eating disorders, cachexia, inflammation, anxiety, Bartholomew's syndrome, or Alstrom syndrome. In embodiments, the disorder is obesity, type 1 diabetes, or type 2 diabetes. In embodiments, the disorder is obesity or an obesity-related condition. In embodiments, the disorder is Prad-Willi syndrome. In embodiments, the disorder is Bartholomew's syndrome. In embodiments, the disorder is Alstrom syndrome. In embodiments, the disorder to be treated involves a disorder associated with or caused by one or more mutations in genes related to the leptin-melanocortin pathway or the POMC-MC4R pathway (such as leptin, leptin receptor, promelanocortin (POMC), prohormone-converting enzyme (e.g., PCSK1), or α-MSH).

[0643] definition

[0644] As used herein, “naturally derived” means a compound isolated from a natural source, and a compound synthesized, either wholly or partially, having the same or substantially the same structure as a naturally occurring compound.

[0645] The compositions and methods disclosed herein cover polypeptides and nucleic acids having a specified sequence, or a sequence substantially identical or similar thereto (e.g., a sequence at least 85%, 90%, 95% or more identical to a specified sequence). In the context of amino acid sequences, the term “substantially identical” is used herein to refer to a first amino acid containing a sufficient or minimum number of the following amino acid residues: i) identical to a corresponding amino acid residue in a second amino acid sequence, or ii) a conserved substitution of a corresponding amino acid residue in a second amino acid sequence, such that the first and second amino acid sequences may have a shared domain and / or shared functional activity. For example, an amino acid sequence containing a shared domain has at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with a reference sequence (e.g., the sequence provided herein).

[0646] Preparations

[0647] Pharmaceutical products may include, for example, the pharmaceutical products and buffers described herein containing: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11). The pH of the formulation is typically pH 5.5–7.0.

[0648] In this embodiment, the pharmaceutical product is a liquid formulation with low viscosity. In this embodiment, the pharmaceutical product is formulated for direct injection, for example, without the need for further addition or adjustment prior to injection. In this embodiment, the pharmaceutical product is stored as a liquid in a device, such as a syringe, as described herein. In this embodiment, the syringe may be selected from: manual syringes, syringes containing a needle (e.g., a needle of appropriate diameter, such as a 27 gauge needle), single-use syringes, multi-use syringes, or spring-loaded syringes (e.g., auto-injectors).

[0649] In embodiments, the components of a pharmaceutical product may be prepared as separate liquid or solid (e.g., lyophilized) formulations and stored separately. In embodiments, the components of a pharmaceutical product may be prepared as at least two, such as two, three, four, or five separate components. In embodiments, the components, such as at least two components containing the pharmaceutical product, may be combined, mixed, dissolved, or dispersed shortly before injection. In embodiments, the components, such as at least two components containing the pharmaceutical product, may be prepared and stored in separate containers, such as at least two separate containers, such as those described herein, and mixed by combining the components, such as at least two components, into one container, such as those described herein. In embodiments, the components, such as at least two components containing the pharmaceutical product, may be combined into one container (e.g., a container having more than one chamber, such as a container with at least two chambers), which separates the components, such as at least two components, by a pharmaceutically acceptable seal, such as maintaining the components, such as at least two components, in separate chambers within that one container (e.g., the container described herein). In embodiments, the seal may be manipulated, such as opening or removing, to mix the components, such as at least two components containing the pharmaceutical product, to form a single solution or suspension in the container. In embodiments, a solution or suspension of the pharmaceutical product may be loaded into a syringe, such as the syringe described herein. In embodiments, the solution or suspension of the pharmaceutical product may be administered to a subject in need, such as the subject described herein, in an effective amount (e.g., a therapeutically effective amount).

[0650] In embodiments, the container may be selected from: syringes, such as manual syringes, syringes containing a needle (e.g., a needle of appropriate diameter, such as a 27 gauge needle), single-use syringes, multiple-use syringes, or spring-loaded syringes (e.g., auto-injectors); vials (single-use vials or multiple-use vials); or other pharmaceutically acceptable containers.

[0651] In the embodiments, the containers described herein include, but are not limited to: Vetter Lyo-ject® dual-chamber syringes, Vetter V-LK® dual-chamber cartridges, Credence Companion® dual-chamber or other dual-chamber devices, such as cartridges or syringes.

[0652] buffer solution

[0653] As used herein, the term "buffer solution" refers to an excipient that stabilizes the pH of a pharmaceutical composition. Examples of buffer solutions include histidine buffer, citrate buffer, succinate buffer, acetate buffer, and phosphate buffer, or mixtures thereof. In examples, the buffer solution of the pharmaceutical product comprises citrate, L-histidine, or a mixture of L-histidine and L-histidine hydrochloride. In examples, the buffer solution of the pharmaceutical product is acetate buffer. The pH may be adjusted with acids or bases, such as hydrochloric acid, acetic acid, phosphoric acid, sulfuric acid, citric acid, sodium hydroxide, and potassium hydroxide, depending on the buffer solution used.

[0654] The pH of the pharmaceutical products described herein is typically between pH 5.0 and 7.5, for example, pH 5.5 to 6.5, pH 5.5 to 6.0, pH 6.0 to 6.5, pH 6.5 to 7.0, pH 5.5, pH 6.0, pH 6.5, or pH 7.0. In examples, buffer solutions maintained at pH 5.5 to pH 7.0 can be used to prepare pharmaceutical products. In examples, buffer solutions used to prepare pharmaceutical products include, but are not limited to, citric acid, HEPES, histidine, arginine, potassium acetate, potassium citrate, potassium phosphate (K₂HPO₄), sodium acetate, sodium bicarbonate, sodium citrate, sodium phosphate (NaH₂PO₄), Tris base, and Tris-HCl. In examples, the concentration of the buffer solution is between 5 mM and 100 mM, for example, 5 mM to 50 mM. In examples, sodium phosphate buffer is used at a concentration of 25 nM. In examples, sodium citrate buffer is used at a concentration of 10 mM or 25 mM. In this example, histidine buffer was used at a concentration of 25 mM. In this example, arginine buffer was used at a concentration of 25 mM.

[0655] Numbered Examples

[0656] The invention is further described with reference to the embodiments numbered below.

[0657] 1. A composition or formulation, such as a composition of a pharmaceutical product, comprising:

[0658] a) Neutral diacyl lipids and / or tocopherols;

[0659] b) Phospholipids:

[0660] c) Alcohols;

[0661] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0662] e) Cymelan peptides, such as cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0663] 2. A composition or formulation, such as a composition of a pharmaceutical product, comprising:

[0664] a) Neutral diacyl lipids and / or tocopherols;

[0665] b) Phospholipids:

[0666] c) Alcohols;

[0667] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0668] e) Semelan peptide.

[0669] 3. A composition or formulation, such as a composition of a pharmaceutical product, comprising:

[0670] a) Neutral diacyl lipids and / or tocopherols;

[0671] b) Phospholipids:

[0672] c) Alcohols;

[0673] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0674] e) Semelan peptide, which is the only active pharmaceutical ingredient formulated for injection.

[0675] 4. A composition or formulation, such as a composition of a pharmaceutical product, comprising:

[0676] a) Neutral diacyl lipids and / or tocopherols;

[0677] b) Phospholipids:

[0678] c) Alcohols;

[0679] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0680] e) Semelan peptide as an active pharmaceutical ingredient.

[0681] 5. A composition or formulation, such as a composition of a pharmaceutical product, comprising:

[0682] a) Neutral diacyl lipids and / or tocopherols;

[0683] b) Phospholipids:

[0684] c) Alcohols;

[0685] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0686] e) Semelan peptide as an active pharmaceutical ingredient for injection.

[0687] 6. A composition or formulation, such as a composition of a pharmaceutical product, comprising:

[0688] a) Neutral diacyl lipids and / or tocopherols;

[0689] b) Phospholipids:

[0690] c) Alcohols;

[0691] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0692] e) MC4RA P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0693] 7. A composition or formulation, such as a composition of a pharmaceutical product, comprising:

[0694] a) Neutral diacyl lipids and / or tocopherols;

[0695] b) Phospholipids:

[0696] c) Alcohols;

[0697] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0698] e) MC4RA as the sole active ingredient P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0699] 8. A composition or formulation, such as a composition of a pharmaceutical product, comprising:

[0700] a) Neutral diacyl lipids and / or tocopherols;

[0701] b) Phospholipids:

[0702] c) Alcohols;

[0703] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0704] e) MC4RA as the sole active ingredient for injection P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0705] 9. A composition or formulation, such as a composition of a pharmaceutical product, comprising:

[0706] a) Neutral diacyl lipids and / or tocopherols;

[0707] b) Phospholipids:

[0708] c) Alcohols;

[0709] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0710] e) MC4RA as an active pharmaceutical ingredient P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0711] 10. A composition or formulation, such as a composition of a pharmaceutical product, comprising:

[0712] a) Neutral diacyl lipids and / or tocopherols;

[0713] b) Phospholipids:

[0714] c) Alcohols;

[0715] d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and

[0716] e) MC4RA as an active pharmaceutical ingredient for injection P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0717] 11. The composition as described in any of the foregoing embodiments, wherein the composition comprises a neutral diacyl lipid.

[0718] 12. The composition as described in Example 11, wherein the neutral diacyl lipid comprises diglyceride.

[0719] 13. The composition of any one of Examples 11-12, wherein the neutral diacyl lipid comprises glyceryl dioleate (GDO).

[0720] 14. The composition as described in any of the foregoing embodiments, wherein the phospholipid comprises phosphatidylcholine.

[0721] 15. The composition as described in any of the foregoing embodiments, wherein the phospholipid comprises soybean phosphatidylcholine.

[0722] 16. The composition as described in any of the foregoing embodiments, wherein the alcohol comprises ethanol.

[0723] 17. The composition as described in any of the foregoing embodiments, wherein the alcohol is provided in a sufficiently large amount to provide a solubility of at least 10 mg / g, 20 mg / g, or 30 mg / g of cermelan peptide.

[0724] 18. The composition as described in Example 17, wherein the amount of ethanol is greater than 1% by weight, for example, between 1 and 20% by weight.

[0725] 19. The composition of any one of Examples 17-18, wherein the amount of ethanol is low enough to allow the subject, such as the subject described herein, to easily and comfortably administer the injection using a device such as an syringe.

[0726] 20. The composition as described in any one of Examples 17-19, wherein the amount of ethanol is less than 20%, 15% or 10% by weight.

[0727] 21. The composition as described in any one of Examples 17-20, wherein the amount of ethanol is large enough to give the composition a sufficiently low viscosity for comfortable delivery by means of a syringe, for example, a syringe with a fine needle, such as a 27 gauge needle.

[0728] 22. The composition as described in any one of Examples 17-21, wherein the amount of ethanol is...

[0729] Sufficiently low so that the initial burst release of the drug after subcutaneous injection, before the administration of the next dose, produces a plasma concentration (C0) of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2 or less). max ) and minimum concentration in plasma (C min The ratio of ).

[0730] 23. The composition as described in any one of Examples 17-22, wherein the amount of ethanol is:

[0731] Sufficiently low so that, upon injection, the drug product provides cermelan peptide; cermelan peptide as the sole active pharmaceutical ingredient formulated for injection; or MC4RA. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) low initial release.

[0732] 24. The composition as described in Example 23, wherein the low initial release is

[0733] The area under the drug concentration-time curve relative to the 7-day steady-state dosing interval is measured by the portion of the drug concentration curve under the curve during the first few hours after dosing (e.g., the first 6 hours), and this portion is less than 10% or less.

[0734] 25. The composition as described in Example 23, wherein the low initial release is the area under the drug concentration-time curve relative to the 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 12 hours) after dosing, the area being less than 10%-20% or less.

[0735] 26. The composition as described in Example 23, wherein the low initial release is

[0736] The area under the drug concentration-time curve relative to the 7-day steady-state dosing interval is measured by the portion of the drug concentration curve under the curve during the first few hours after dosing (e.g., the first 24 hours), and this portion is less than 20%-30% or less.

[0737] 27. The composition as described in Example 19, wherein the device may be a single-use device or a multiple-use device.

[0738] 28. The composition as described in Example 19, wherein the device is selected from: a manual syringe (e.g., a syringe containing a needle (e.g., a needle of suitable diameter, such as a 27 gauge needle)) or an auto-injector (e.g., a spring-loaded syringe or a pen syringe).

[0739] 29. The composition as described in any of the foregoing embodiments, wherein the polar solvent, such as a buffer solution, comprises a citrate buffer solution, optionally wherein the pH of the buffer solution is 6.4.

[0740] 30. The composition as described in any of the foregoing embodiments, wherein the polar solvent, such as a buffer solution, comprises citrate monohydrate.

[0741] 31. The composition as described in any of the foregoing embodiments, wherein the polar solvent, such as a buffer solution, contains additional components, such as an antioxidant or a chemical or physical stabilizer.

[0742] 32. The composition as described in Example 31, wherein the antioxidant is EDTA.

[0743] 33. The composition as described in any of the foregoing embodiments, wherein the polar solvent, such as a buffer solution, comprises citrate monohydrate, disodium EDTA, and water.

[0744] 34. The composition as described in any of the foregoing embodiments, wherein cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11) exist as chloride salts.

[0745] 35. The composition as described in any of the foregoing embodiments, wherein the pharmaceutical product optionally comprises an antimicrobial agent or a microbial inhibitor, such as an antibacterial agent or a preservative.

[0746] 36. The composition as described in any of the foregoing embodiments, wherein the weight ratio of a:b is 70:30 to 40:60.

[0747] 37. The composition as described in any of the preceding embodiments, wherein the weight ratio of a:b is 70:30, 65:45, 60:40, 55:45, 50:50, 45:55 or 40:60.

[0748] 38. The composition as described in any of the foregoing embodiments, wherein component a is 20%-80%, 30%-70%, 33%-60%, or 38%-43% by weight of the total weight of the solutions of components a, b, and c.

[0749] 39. The composition as described in any of the foregoing embodiments, wherein component b is 20%-80%, 30%-70%, 33%-60%, or 38%-43% by weight of the total weight of the solutions of components a, b, and c.

[0750] 40. The composition as described in any of the foregoing embodiments, wherein component c, for example ethanol, is 0.5%-50%, 2%-30%, or 5%-20% by weight of the total weight of the solutions of components a, b, and c.

[0751] 41. The composition as described in any of the foregoing embodiments, wherein,

[0752] This neutral diacyl lipid contains dioleoyl glycerol ester;

[0753] This phospholipid contains phosphatidylcholine;

[0754] This alcohol contains ethanol; and

[0755] The polar solvent, such as a buffer solution, contains citrate buffer.

[0756] 42. The composition as described in any of the foregoing embodiments, wherein,

[0757] This neutral diacyl lipid contains dioleoyl glycerol ester;

[0758] This phospholipid contains soybean phosphatidylcholine;

[0759] This alcohol contains ethanol; and

[0760] The polar solvent, such as a buffer solution, contains citrate buffer at pH 6.4 containing EDTA.

[0761] 43. The composition as described in any of the foregoing embodiments, wherein each milliliter of the composition comprises:

[0762] 420 + / - 20% mg dioleoglycerate (GDO);

[0763] 420 + / - 20% mg soybean phosphatidylcholine;

[0764] 105 + / - 20% mg ethanol;

[0765] 20 + / - 20% mg citrate buffer; and

[0766] 30 + / - 20% mg cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0767] 44. The composition as described in any of the foregoing embodiments, wherein each milliliter of the composition comprises:

[0768] 420 + / - 10% mg dioleoglycerate (GDO);

[0769] 420 + / - 10% mg soybean phosphatidylcholine;

[0770] 105 + / - 10% mg ethanol;

[0771] 20 + / - 10% mg citrate buffer; and

[0772] 30 + / - 10% mg cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0773] 45. The composition as described in any of the foregoing embodiments, wherein each milliliter of the composition comprises:

[0774] 420 + / - 5% mg dioleoglycerate (GDO);

[0775] 420 + / - 5% mg soybean phosphatidylcholine;

[0776] 105 + / - 5% mg ethanol;

[0777] 20 + / - 5% mg citrate buffer; and

[0778] 30 + / - 5% mg cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0779] 46. ​​The composition as described in any of the foregoing embodiments, wherein each milliliter of the composition comprises:

[0780] 420 + / - 2% mg dioleoglycerate (GDO);

[0781] 420 + / - 2% mg soybean phosphatidylcholine;

[0782] 105 + / - 2% mg ethanol;

[0783] 20 + / - 2% mg citrate buffer; and

[0784] 30 + / - 2% mg cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0785] 47. The composition as described in any of the foregoing embodiments, wherein each milliliter of the composition comprises

[0786] 419.8 mg dioleoylglycerol (GDO);

[0787] 419.8 mg soybean phosphatidylcholine;

[0788] 105 mg ethanol;

[0789] 20 mg citrate buffer; and

[0790] 30 mg cermelan peptide.

[0791] 48. The composition as described in any of the foregoing embodiments, wherein the composition comprises:

[0792] The neutral diacyl lipid of component a, which, by weight, constitutes 20%-80%, 30%-70%, 33%-60%, or 38%-43% of components a, b, and c; components a, b, c, d, and e in the composition;

[0793] The phospholipid of component b, by weight, constitutes 20%-80%, 30%-70%, 33%-60%, or 38%-43% of components a, b, c, and d of the composition; or components a, b, c, d, and e.

[0794] The alcohol of component c, which, by weight, constitutes 0.1%-35%, 5%-20%, 8%-15%, or 9%-11% of components a, b, c, and d in the composition; or components a, b, c, d, and e.

[0795] The polar solvent of component d, such as a buffer solution, constitutes, by weight, 0.5%-10%, 1%-5%, or 1%-3% of components a, b, and c; components a, b, c, and d; or components a, b, c, d, and e; and

[0796] Semelan peptide; semelan peptide as the sole active pharmaceutical ingredient formulated for injection; semelan peptide as the sole active ingredient; semelan peptide as an active pharmaceutical ingredient; semelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), comprising, by weight, 0.1%-10%, 0.2%-8%, 0.5%-6%, and 1%-4% of components a, b, and c; components a, b, c, and d; or components a, b, c, d, and e.

[0797] 49. The composition as described in any of the foregoing embodiments, wherein the composition comprises:

[0798] Neutral diacyl lipids, which, by weight, constitute 42% + / - 10, 42% + / - 5, 42% + / - 2, or 42% + / - 1 of components a, b, c, d, and e in the composition;

[0799] Phospholipids, by weight, comprising 42% + / - 10, 42% + / - 5, 42% + / - 2 or 42% + / - 1 of components a, b, c, d, and e in the composition;

[0800] An alcohol, by weight, comprising 10% + / - 8, 10% + / - 6, 10% + / - 5, or 10% + / - 1 of components a, b, c, d, or e in the composition;

[0801] A polar solvent, such as a buffer solution, comprising, by weight, 2% + / - 1, 2% + / - 0.5, 2% + / - 0.25, or 2% + / - 0.1% of components a, b, c, d, and e in the composition; and

[0802] Cymerlan peptide or MC4RA P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11), which, by weight, constitute 3% + / - 1.5, 3% + / - 1 or 3% + / - 0.5 of components a, b, and c; components a, b, c, and d; or components a, b, c, d, and e.

[0803] 50. The composition as described in any of the preceding embodiments, wherein the composition, upon contact with an aqueous environment, such as by injection, for example by subcutaneous injection into a subject, forms or is capable of forming at least one liquid crystalline structure.

[0804] 51. The composition as described in any of the foregoing embodiments, wherein the viscosity is:

[0805] (i) low enough to be comfortably delivered by a device, such as a syringe with a fine needle, such as a 27 gauge needle;

[0806] (ii) Low enough to cause semelanide or MC4RA to be ineffective after injection and before the next dose is administered. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) after subcutaneous injection, the initial burst release from the drug product, for example, produces a maximum plasma concentration (C0.05) of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, or less)). max ) and minimum concentration in plasma (C min The ratio of ); or

[0807] (iii) Low enough to provide ceramide peptide or MC4RA after injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) low initial release.

[0808] 52. The composition as described in any of the foregoing embodiments, wherein when injected into a subject:

[0809] i) Before administering the next dose of ceramide peptide or MC4RA P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) after subcutaneous injection, the initial burst release from the drug product, for example, produces a maximum plasma concentration (C0.05) of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, or less)). max ) and minimum concentration in plasma (C min The ratio of ); or

[0810] ii) The drug product provides cermelan peptide or MC4RA. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) low initial release.

[0811] 53. The composition as described in Examples 51 or 52, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 6 hours) after dosing, the area being less than 10% or less.

[0812] 54. The composition as described in Example 51 or 52, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 12 hours) after dosing, the area being less than 10%-20% or less.

[0813] 55. The composition as described in Examples 51 or 52, wherein the low initial release is the area under the drug concentration-time curve relative to a 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 24 hours) after dosing, the area being less than 20%-30% or less.

[0814] 56. The composition as described in any of the foregoing embodiments, wherein the composition comprises cermelan peptide.

[0815] 57. The composition of any one of Examples 1-55, wherein the composition comprises cermelan peptide as the sole active pharmaceutical ingredient formulated for injection.

[0816] 58. The composition as described in any one of Examples 1-55, wherein the composition comprises cermelan peptide as the sole active ingredient.

[0817] 59. The composition as described in any one of Examples 1-55, wherein the composition comprises cermelan peptide as an active pharmaceutical ingredient.

[0818] 60. The composition of any one of Examples 1-55, wherein the composition comprises cermelan peptide as an active pharmaceutical ingredient for injection.

[0819] 61. The composition of any one of Examples 1-55, wherein the composition comprises MC4RA P (For example, as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection).

[0820] 62. The composition of any one of Examples 1-55, wherein the composition comprises BIM-22511.

[0821] 63. The composition of any one of Examples 1-55, wherein the composition comprises BIM-22287.

[0822] 64. The composition of any one of Examples 1-55, wherein the composition comprises BIM-22512.

[0823] 65. The composition of any one of Examples 1-55, wherein the composition comprises 001152C.

[0824] 66. The composition of any one of Examples 1-55, wherein the composition comprises 001543C.

[0825] 66a. The composition as described in any one of Examples 1-55, wherein the composition comprises 001003C.

[0826] 66b. The composition of any one of Examples 1-55, wherein the composition comprises 001574C.

[0827] 66c. The composition of any one of Examples 1-55, wherein the composition comprises 001555C.

[0828] 66d. The composition as described in any one of Examples 1-55, wherein the composition comprises 001554C.

[0829] 66e. The composition as described in any one of Examples 1-55, wherein the composition comprises 001556C.

[0830] 66f. The composition as described in any one of Examples 1-55, wherein the composition comprises 001358C.

[0831] 66g. The composition as described in any one of Examples 1-55, wherein the composition contains 001576C.

[0832] 66h. The composition as described in any one of Examples 1-55, wherein the composition comprises 001364C.

[0833] 66i. The composition as described in any one of Examples 1-55, wherein the composition comprises 001258C.

[0834] 66j. The composition as described in any one of Examples 1-55, wherein the composition comprises MC4R-11.

[0835] 67. A unit dosage form comprising the composition as described in any one of Examples 1-76.

[0836] 68. The unit dosage form as described in Example 67, comprising a composition of at least 2, 1.8, 1.6, 1.4, 1.2, 1, 0.8, 0.6, 0.4, or 0.2 mL.

[0837] 69. The unit dosage form as described in any one of Examples 67-68, wherein the unit dosage form is disposed in a liquid-tight outer casing, such as a vial or cartridge.

[0838] 70. The unit dosage form as described in any one of Examples 67-69, wherein the unit dosage form is disposed in an injection device, such as a single-use device or a multiple-use device.

[0839] 71. The unit dosage form as described in Example 70, wherein the device is selected from: a manual syringe (e.g., a syringe containing a needle (e.g., a needle of suitable diameter, such as a 27 gauge needle)) or an auto-injector (e.g., a spring-loaded syringe or a pen syringe).

[0840] 72. A unit dosage form as described in any one of Examples 67-71, comprising 10-70; 20-60; 25-50; 25-40; 25-35 mg of cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0841] 73. A unit dosage form as described in any one of Examples 67-71, comprising 50 + / - 20%; 40 + / - 20%; or 30 + / - 20% mg of cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as the active pharmaceutical ingredient; cymelan peptide as the active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, the active pharmaceutical ingredient, or the active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0842] 74. A unit dosage form as described in any one of Examples 67-71, comprising 50 + / - 10%; 40 + / - 10%; or 30 + / - 10% mg of cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as the active pharmaceutical ingredient; cymelan peptide as the active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, the active pharmaceutical ingredient, or the active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0843] 75. A unit dosage form as described in any one of Examples 67-71, comprising 50 + / - 5%; 40 + / - 5%; or 30 + / - 5% mg of cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, the sole active ingredient for injection, an active pharmaceutical ingredient, or an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0844] 76. A unit dosage form as described in any one of Examples 67-71, wherein the unit dosage form comprises 40, 35, or 30 mg of cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0845] 77. The unit dose as described in any one of Examples 67-76, wherein the composition is suitable for injection, such as subcutaneous or intramuscular injection.

[0846] 78. The unit dosage form as described in any one of Examples 67-77, wherein the viscosity is:

[0847] i) Low enough to be comfortably delivered by a device, such as a syringe with a fine needle, such as a 27-gauge needle;

[0848] ii) Low enough to ensure that the concentration of ceramide peptide or MC4RA is low after injection and before the next dose is administered. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) after subcutaneous injection, the initial burst release from the drug product, for example, produces a maximum plasma concentration (C0.05) of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, or less)). max ) and minimum concentration in plasma (C min The ratio of ); or

[0849] iii) Low enough to provide ceramide peptide or MC4RA after injection. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) low initial release.

[0850] 79. The unit dosage form as described in any one of Examples 67-77, wherein when injected into a subject:

[0851] i) Before administering the next dose of ceramide peptide or MC4RA P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) after subcutaneous injection, the initial burst release from the drug product, for example, produces a maximum plasma concentration (C0.05) of less than 8 (e.g., less than 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, 2, or less)). max ) and minimum concentration in plasma (C min The ratio of ); or

[0852] ii) The drug product provides cermelan peptide or MC4RA. P (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) low initial release.

[0853] 80. The unit dosage form as described in Examples 78 or 79, wherein the low initial release is the area under the drug concentration-time curve relative to the 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 6 hours) after dosing, which is less than 10% or less.

[0854] 81. The unit dosage form as described in Example 78 or 79, wherein the low initial release is the area under the drug concentration-time curve relative to the 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours (e.g., the first 12 hours) after dosing, which is less than 10%-20% or less.

[0855] 82. The unit dosage form as described in Examples 78 or 79, wherein the low initial release is the area under the drug concentration-time curve relative to the 7-day steady-state dosing interval, measured by the area under the drug concentration curve during the first few hours after dosing (e.g., the first 24 hours), which is less than 20%-30% or less.

[0856] 83. A method of manufacturing a formulation or composition, such as a pharmaceutical composition, for example a formulation or composition having a controlled level of EtOH, the formulation or composition comprising component (e), the component (e) comprising: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), the method includes:

[0857] i) Provide a mixture containing either ceramide peptide or MC4RA. P (e., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) component (e), a first amount of EtOH and one or more of the following components:

[0858] a) Neutral diacyl lipids and / or tocopherols;

[0859] b) Phospholipids;

[0860] c) alcohols; and

[0861] d) Polar solvents, such as buffer solutions; and

[0862] ii) Add a second amount of EtOH.

[0863] This manufactures formulations or compositions, such as pharmaceutical compositions, comprising component (e), which comprises: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P(For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0864] 84. The method as described in Example 83, wherein forming the mixture is provided.

[0865] 85. The method as described in any one of Examples 83-84, wherein the addition of the second amount of EtOH results in an amount of EtOH that satisfies a reference value, for example, falling within a range of values, for example, falling within a range defined by a lower limit and an upper limit, for example, the upper and lower limits of weight % EtOH, for example, 10-0.5 weight %.

[0866] 86. The method as described in Example 85, wherein the reference value is a value in the range of 5 to 20; 8.5 to 12.5; and 9 to 11 wt% EtOH, for example, 10 wt%.

[0867] 87. The method as described in Example 85, wherein the reference value is a value in the range of 9 to 11 wt% EtOH, for example 10 wt%.

[0868] 88. The method of any one of Examples 83-87, wherein the method comprises determining the amount of EtOH in the mixture by appropriate analytical determination.

[0869] 89. The method of Example 88, wherein the method includes, in response to the determination, selecting the amount of EtOH to be added to the mixture, for example, the amount to reach the reference value.

[0870] 90. The method of Example 89, wherein the method comprises adding a selected amount of EtOH to the mixture to form an EtOH-replenished mixture.

[0871] 91. The method as described in Example 90, wherein the selected amount is added to the mixture as a single aliquot or as multiple aliquots of the same or different amounts.

[0872] 92. The method of any one of Examples 83-91, wherein less than 48 hours, less than 24 hours, or less than 4 hours have elapsed between the formation of the mixture and the determination of the amount of EtOH in the mixture, the selection of the amount of EtOH to be added, or the addition of the second amount.

[0873] 93. The method as described in any one of Examples 83-91, the method comprising providing the amount of the component to be added to the mixture.

[0874] 94. The method as described in Example 93, wherein providing includes weighing the amount of components added to the mixture.

[0875] 95. The method as described in any one of Examples 83-94, the method comprising providing a value for the amount of EtOH in the mixture and determining the amount of EtOH to be added to satisfy a reference for the amount of EtOH.

[0876] 96. The method as described in any one of Examples 83-95, wherein after the mixture is formed, EtOH is lost from the mixture, for example by evaporation, such as evaporation into the top space of a container, such as a mixing vessel.

[0877] 97. The method as described in any one of Examples 83-96, wherein after the second amount is added to the mixture, the amount of EtOH in the EtOH-replenished mixture is determined.

[0878] 98. The method as described in Example 97, the method comprising, in response to the determination, selecting the amount of EtOH to be added to the mixture to which the EtOH is replenished.

[0879] 99. The method as described in Example 98, wherein the method comprises adding a selected amount of EtOH to the EtOH-replenished mixture to form a two-replenished mixture.

[0880] 100. The method of any one of Examples 83-99, further comprising providing a second formulation or composition, such as a pharmaceutical product, the second formulation or composition comprising component (e) comprising cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0881] 101. The method as described in any one of Examples 83-100, the method comprising:

[0882] The preparation comprises a component (e) containing ceramide peptide, EtOH, neutral diacyl lipids and / or tocopherols and phospholipids.

[0883] Among them, cermelan peptide or MC4RA P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) and EtOH, then add one or two of neutral diacyl lipids and / or tocopherols, and phospholipids.

[0884] This manufactures a composition or formulation, such as a pharmaceutical product, having component (e), which comprises: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0885] 102. The method as described in any one of Examples 83-100, the method comprising:

[0886] The mixture is prepared by comprising: containing ceramide peptide or MC4RA. P (e., components (e.g., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11), water or polar solvents (e.g., buffer solutions), neutral diacyl lipids and / or tocopherols and phospholipids,

[0887] This includes containing cermelan peptide or MC4RA. P(e., BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C, or MC4R-11) components (e) are combined with water or a polar solvent (e.g., buffer solution), and then one or both of neutral diacid lipids and / or tocopherols, and phospholipids are added.

[0888] This manufactures a composition or formulation, such as a pharmaceutical product, having component (e), which comprises: cymelan peptide; cymelan peptide as the sole active pharmaceutical ingredient formulated for injection; cymelan peptide as the sole active ingredient; cymelan peptide as an active pharmaceutical ingredient; cymelan peptide as an active pharmaceutical ingredient for injection; or MC4RA as the sole active ingredient, as the sole active ingredient for injection, as an active pharmaceutical ingredient, or as an active pharmaceutical ingredient for injection. P (For example, BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11).

[0889] 103. The method as described in any one of Examples 83-102, wherein the mixture is formed in the following order:

[0890] i) Containing ceramide peptide or MC4RA P (e) of BIM-22511, BIM-22287, BIM-22512, 001152C, 001543C, 001003C, 001574C, 001555C, 001554C, 001556C, 001358C, 001576C, 001364C, 001258C or MC4R-11) is contacted with EtOH (and optionally water or a polar solvent, such as a buffer solution);

[0891] ii) Add the phospholipid to the mixture obtained from i); and

[0892] iii) Add the neutral diacyl lipid and / or tocopherol to the mixture obtained from ii).

[0893] 104. The met...

Claims

1. An injectable composition or formulation, such as an injectable composition of a pharmaceutical product, comprising: a) Neutral diacyl lipids and / or tocopherols; b) Phospholipids: c) Alcohols; d) Optionally, a polar solvent, such as a buffer solution, optionally containing an antioxidant; and e) Semelan peptide, which is the only active pharmaceutical ingredient.

2. The injectable composition of claim 1, wherein the injectable composition comprises a neutral diacyl lipid.

3. The injectable composition of claim 4, wherein the neutral diacyl lipid comprises diglyceride.

4. The injectable composition of claim 4, wherein the neutral diacyl lipid comprises glyceryl dioleate (GDO).

5. The injectable composition of claim 1, wherein the phospholipid comprises phosphatidylcholine (e.g., soybean phosphatidylcholine).

6. The injectable composition of claim 1, wherein the alcohol comprises ethanol.

7. The injectable composition of claim 6, wherein the ethanol is provided in a sufficiently large amount to provide solubility of at least 10 mg / g, 20 mg / g, or 30 mg / g of cermelan peptide.

8. The injectable composition of claim 6, wherein the amount of ethanol is greater than 1% by weight, for example, between 1 and 20% by weight.

9. The injectable composition of claim 6, wherein the amount of ethanol is low enough to allow a subject, such as the subject described herein, to easily and comfortably administer the injection using a device such as an syringe.

10. The injectable composition of claim 6, wherein the amount of ethanol is less than 20%, 15% or 10% by weight.

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