GIP / GLP1 agonist compositions

Abstract

To provide a pharmaceutical GIP / GLP1 co-agonist peptide composition for subcutaneous injection.SOLUTION: The present invention provides a pharmaceutical composition for treating diabetes, comprising tirzepatide or a pharmaceutically acceptable salt thereof, and an agent selected from the group consisting of NaCl and propylene glycol, where the pharmaceutical composition has a pH of about 6.5 to about 7.5. The pharmaceutical composition is preferably administered using an automatic injection apparatus.SELECTED DRAWING: None

Description

[Background technology]

[0001] The present invention is a pharmaceutical GIP / GLP1 coagonist peptide composition for subcutaneous injection. The composition comprises tirzepatide, NaCl, and dibasic sodium phosphate. The product provides commercially acceptable shelf-life stability, in-use stability, and acceptable patient The alternative composition is tirzepatide, propylene glycol and dibasic sodium phosphate, which also provides acceptable shelf-life stability. .

[0002] Diabetes mellitus is hyperglycemia caused by defects in insulin secretion, insulin action, or both. Type 2 diabetes ("T2D") is a chronic disease characterized by insufficient insulin secretion and The combined effects of hypercalcemia and insulin resistance are associated with elevated blood glucose levels. Patid is a GIP / GLP1 co-agonist peptide useful in the treatment of diabetes. Patides are useful in the treatment of obesity.

[0003] US9474780 is a GIP / GLP drug that is generally administered by parenteral route. US9474780 describes compositions containing tirzepatide. Describes and claims acceptable stability and acceptable patient injection site experience. Compositions of tirzepatide which provide the following are desirable.

[0004] The present invention relates to a pharma- ceutical acceptable composition of tirzepatide or a pharma- ceutical acceptable salt thereof. The composition comprises an agent selected from the group consisting of NaCl and propylene glycol, and These needs are addressed by providing a composition comprising: is attempting to fill.

[0005] In one embodiment, the agent is NaCl. In one embodiment, the NaCl concentration is about 6. 2 mg / mL to about 9.5 mg / mL. In one embodiment, the NaCl concentration is about 7.0 mg / mL to about 9.0 mg / mL. In one embodiment, the NaCl concentration is about 8.2 m g / mL.

[0006] In one embodiment, the agent is propylene glycol. In one embodiment, propylene glycol concentration is about 12.0 mg / mL to about 18.0 mg / mL. In one embodiment the propylene glycol concentration is about 14.0 mg / mL to about 16.0 mg / mL . In one embodiment, the propylene glycol concentration is about 15.0 mg / mL.

[0007] In one embodiment, the dibasic sodium phosphate concentration is about 0.67 mg / mL to about 2.6 8 mg / mL. In one embodiment, the dibasic sodium phosphate is about 1.0 mg / m L to about 3.0 mg / mL. In one embodiment, the dibasic sodium phosphate is about 1. 34 mg / mL.

[0008] In one embodiment, the tildepazide concentration is about 5 mg / mL to about 30 mg / mL, and the agent is NaCl. In one embodiment, the tildepazide concentration is about 10 mg / mL to about 3 0 mg / mL. In one embodiment, the tildepazide concentration is about 5 mg / mL to about 30 m g / mL, the NaCl concentration is about 8.2 mg / mL, and the dibasic sodium phosphate concentration is about 0.67 mg / mL to about 2.68 mg / mL. In one embodiment, til The zepotid concentration is from about 5 mg / mL to about 30 mg / mL, and the NaCl concentration is about 8.2 mg / mL, and the dibasic sodium phosphate concentration is from about 0.67 mg / mL to about 2.6 8 mg / mL, and the composition is provided in a single-use auto-injector device.

[0009] In one embodiment, the zepotid concentration is from about 5 mg / mL to about 30 mg / mL, and the drug is propylene glycol. In one embodiment, the zepotid is from about 5 mg / mL to about 30 mg / mL, and the propylene glycol is from about 12.0 mg / mL to about 18. 0 mg / mL, and the dibasic sodium phosphate concentration is about 1.34 mg / mL. In one embodiment, the zepotid concentration is from about 5 mg / mL to about 30 mg / mL, and the pro pylene glycol is about 15.0 mg / mL, and the dibasic sodium phosphate concentration is about 1.34 mg / mL.

[0010] In one embodiment, the zepotid concentration is from about 5 mg / mL to about 30 mg / mL. Spec ific embodiments have a zepotid concentration from about 10 mg / mL to about 30 mg / mL. In one embodiment, the zepotid concentration is selected from the group consisting of 5, 10, 15, 20, 25, and 30 mg / mL. In one embodiment, a composition of 0.5 mL or less is administered as a dose. In one embodiment, the zepotid concentration is selected from the group consisting of 10, 20, and 30 mg / m L.

[0011] In one embodiment, the zepotid composition further comprises a preservative. In one embodiment, the til zepotid composition comprises zepotid, dibasic sodium phosphate, propylene glycol, and a preservative. In one embodiment, the preservative is selected from the group consisting of metacresol and phenol. In one embodiment, the metacresol concentration is from about 2.0 mg / mL to about 4.0 mg / mL. In one embodiment, the metacresol concentration is from about 3.0 mg / m L to about 3.5 mg / mL. In one embodiment, the metacresol concentration is about 3.15 m g / mL. In one embodiment, the phenol concentration is from about 3.0 mg / mL to about 7.0 m g / mL. In one embodiment, the phenol concentration is from about 4.0 mg / mL to about 6.0 m g / mL. In one embodiment, the phenol concentration is about 5.0 mg / mL. In one embodiment, a tiludronate composition is provided, wherein the tiludronate concentration is from about 5 mg / mL to about 30 mg / mL, the propylene glycol concentration is from about 12.0 mg / mL to about 18. 0 mg / mL, the dibasic sodium phosphate concentration is from about 0.67 to about 2.68 mg / mL, and the metacresol concentration is from about 2.0 mg / mL to about 4.0 mg / mL. In one embodiment, the metacresol concentration is about 3.15 mg / mL. In one embodiment , a tiludronate composition is provided, wherein the tiludronate concentration is from about 5 mg / mL to about 30 mg / mL, the propylene glycol concentration is from about 12.0 mg / mL to about 18.0 mg / m L, the dibasic sodium phosphate concentration is from about 0.67 to about 2.68 mg / mL, and , the phenol concentration is from about 3.0 mg / mL to about 7.0 mg / mL. In one embodiment , a tiludronate composition is provided, wherein the tiludronate concentration is from about 5 mg / mL to about 30 mg / mL, the propylene glycol concentration is from about 12.0 mg / mL to about 18.0 mg / m L, the dibasic sodium phosphate concentration is from about 0.67 to about 2.68 mg / mL, and The phenol concentration is about 5.0 mg / mL.

[0012] In one embodiment, the dose of the tilsepamate composition is administered about once a week. In one embodiment, the dose of the tilsepamate composition is administered once every 7 days.

[0013] In one embodiment, a method for treating diabetes, comprising administering to a human in need thereof an effective dose of one of the above compositions, is provided.

[0014] In one embodiment, a method for treating obesity, comprising administering to a human in need thereof an effective dose of one of the above compositions, is provided. In one embodiment, a method for providing therapeutic weight loss, comprising administering to a human in need thereof an effective dose of one of the above compositions, is provided. In one embodiment, a method for treating a condition mediated by GIP / GLP1 core agonist activity, comprising administering to a human in need thereof an effective dose of one of the above compositions, is provided.

[0015] In one embodiment, one of the above compositions is provided for use as a medicament.

[0016] In one embodiment, one of the above compositions is provided for use in the treatment of diabetes. In one embodiment, one of the above compositions is provided for use in the treatment of obesity. is provided.

[0017] In one embodiment, one of the above compositions is provided for use in providing therapeutic weight loss. In one embodiment, one of the above compositions is provided for use in providing non-therapeutic weight loss.

[0018] According to another aspect of the present invention, there is provided a manufactured article comprising one of the above compositions. In particular in certain embodiments, the manufactured article is a multi-use vial. In certain embodiments, the manufactured article is a prefilled syringe. In certain embodiments, the manufactured article is an auto-injector ("autoinjector"). An example of an autoinjector contemplated herein is U.S. Patent No. 8, 734,394.

[0019] As used herein, "tilsempetide" refers to the GIP / GLP1 co agonist peptide described in US9,474,780 and identified by the CAS Registry Number: 2023788-19-2. Tilsempetide has the following sequence, as described in Example 1 of US9474,780, YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPP S wherein X1 is Aib, X2 is Aib, and the K at position 20 is chemically modified through its epsilon-amino group of the K side chain to the bond with (2-[2-(2 -amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2) 18-CO2H, and the C-terminal amino acid is amidated as a C-terminal primary amide (SEQ ID NO: 1).

[0020] As used herein, "pharmaceutically acceptable salts" are well known to those skilled in the art. In one embodiment, it is a pharmaceutically acceptable salt that is the tilsempetide salt of trifluoroacetic acid.

[0021] As used herein, the term "surfactant-free" means that the composition does not contain added It means containing no surfactant or containing only a small amount of added surfactant. It is.

[0022] As used herein, the term "propylene glycol" is well-known to those skilled in the art. It is.

[0023] Propylene glycol is also represented by the formula: C3H8O2.

[0024] The composition of the present invention has a concentration of tilsempide 30 of 5 mg / mL to 30 mg / mL. The composition of the present invention is likely to have specific concentrations of 5, 10, 15, 20, 25, and 30 mg / mL. Such a composition may be provided in a prefilled syringe. Such a prefilled syringe may be useful for administering such a composition at 0.5 milliliters per dose per patient. A dose of the tilsempide composition may be administered using a dosing schedule determined by a physician. It is. It is. It can be administered using a dosing schedule determined by a physician.

[0025] The composition is sterile when first manufactured. When provided in a multi-use vial or cartridge, an antibacterial preservative compound or a mixture of compounds compatible with the other components of the composition may be added at a strength sufficient to meet applicable regulatory antibacterial preservative requirements. Pharmaceutically acceptable preservatives are well-known in the art. (See, for example, Remington: The Science and Practice of Pharmacy (D. B. Troy, Editor, 21st Edition, Lippincott, Williams & Wilkins, 2006)). In one embodiment, the preservative is metacresol. In one embodiment, the preservative is phenol. For single-use It is. It is. It is. n: The Science and Practice of Pharmacy (D . B. Troy, Editor, 21st Edition, Lippincott, W illiams & Wilkins, 2006). In one embodiment, the preservative is metacresol. In one embodiment, the preservative is phenol. For single-use The composition for the refill syringe does not require a preservative. In one embodiment, the composition does not contain a surfactant.

[0026] The pH of the tilsepamate composition of the present invention is typically 6.5 to 7.5, and is adjusted using physiologically appropriate acids and bases as may be required to achieve the desired p H. In one embodiment, the pH target is 6.7 to 7.3. The experience of the patient's injection site is a consideration for the composition administered subcutaneously. It is desirable to select a composition associated with an acceptable patient injection site experience. For example, NaCl and citrate are associated with a stinging sensation with pain at the injection site. (Laursen, T.; Hansen, B.; Fi sker, S. Pain perception after subcutaneou s injections of media containing differe nt buffers. Basic & Clinical Pharmacology & T oxicology 2006, 98, (2), 218 - 221.), (Fransso n, J.; Espander - Jansson, A. Local tolerance of subcutaneous injections. Journal of Ph armacy and Pharmacology 1996, 48, (10), 101 2 - 1015.) Solutions that are not approximately isotonic with body fluids can cause a stinging sensation with pain when administered, so it is further desirable to match the tonicity (i.e., osmotic pressure) of the body fluid at the injection site as closely as possible when administering the composition. The composition is substantially isotonic with body fluid at the injection site ​​​​​It is desirable. The composition containing tilzeyapatide, NaCl, and dibasic sodium phosphate is associated with an acceptable patient injection site experience. Similarly, the composition containing tilzeyapatide, propylene glycol, and dibasic sodium phosphate is associated with an acceptable patient injection site experience.

[0027] In one embodiment, the pH is adjusted using a base to facilitate dissolution in the buffer solution. Addition of an acid to the composition may be required to adjust the pH to the desired pH range. In one embodiment, NaOH is used to facilitate dissolution of tilzeyapatide in the buffer. In one embodiment, HCl is added to adjust the pH of the composition containing dissolved tilzeyapatide to the desired pH range.

[0028] The compositions of the present invention are typically administered subcutaneously. The compositions are typically administered using a prefilled disposable pen, a reusable pen, or an auto - pen injector. The compositions can be administered using a multi - use vial or a pump device. In one embodiment, the device is an auto - injection device described by U.S. Patent No. 8,734,394.

[0029] Compositions containing tilzeyapatide, NaCl, and dibasic sodium phosphate provide desirable shelf - life stability and an acceptable patient injection site experience. Similarly, compositions containing tilzeyapatide, propylene glycol, and dibasic sodium phosphate provide desirable shelf - life stability and an acceptable patient injection site experience. As used herein, "shelf - life stability" is measured under controlled conditions at about 5 degrees Celsius. is obtained. Compositions containing tilzeyapatide, NaCl, and disodium phosphate provide acceptable stability during use. Similarly, compositions containing tilzeyapatide, propylene glycol, and disodium phosphate provide acceptable stability during use. As used herein, the term "stability during use" refers to the stability of the composition measured under controlled conditions at about 25°C or about 40°C. is obtained. Compositions containing tilzeyapatide, propylene glycol, and disodium phosphate provide acceptable stability during use. As used herein, the term "stability during use" refers to the stability of the composition measured under controlled conditions at about 25°C or about 40°C. is obtained. Compositions containing tilzeyapatide, propylene glycol, and disodium phosphate provide acceptable stability during use. As used herein, the term "stability during use" refers to the stability of the composition measured under controlled conditions at about 25°C or about 40°C. As used herein, the term "stability during use" refers to the stability of the composition measured under controlled conditions at about 25°C or about 40°C. As used herein, the term "stability during use" refers to the stability of the composition measured under controlled conditions at about 25°C or about 40°C.

[0030] Example #1 - Composition Containing NaCl The composition is prepared substantially as described herein. Compositions containing 5, 10, 15, 20, 15, and 30 mg / mL of tilzeyapatide each contain the components listed in Table 1. An acid or base is optionally added to achieve the desired pH range. Water is added in an appropriate amount (q.s.) to a total final volume of 1 milliliter. An acid or base is optionally added to achieve the desired pH range. Water is added in an appropriate amount (q.s.) to a total final volume of 1 milliliter. An acid or base is optionally added to achieve the desired pH range. Water is added in an appropriate amount (q.s.) to a total final volume of 1 milliliter. [Table 1]

[0031] Example #2 - Composition Containing Propylene Glycol The composition is prepared substantially as described herein. Compositions providing compositions of 5, 10, 15, 20, 15, and 30 mg / mL of tilzeyapatide each contain the components listed in Table 2. An acid or base is optionally added to achieve the desired pH range. Water is added in an appropriate amount to a total final volume of 1 milliliter. An acid or base is optionally added to achieve the desired pH range. Water is added in an appropriate amount to a total final volume of 1 milliliter. An acid or base is optionally added to achieve the desired pH range. Water is added in an appropriate amount to a total final volume of 1 milliliter. [Table 2]

[0032] Stability Test during Use of Size Exclusion Chromatography (SEC) This procedure is a gradient size exclusion HPLC method with UV detection at 214 nm and is designed to determine the relative amounts of the monomer and total aggregates of thilzepide. The monomer and aggregates are reported as peak area percentages relative to the total area. The procedure demonstrates stability as measured by its ability to degrade known impurities from thilzepide. This test compares an alternative composition with the composition of the present invention prepared as shown in Table 3. The stability from this test is shown in Table 4. Stability test for comparing alternative compositions:

Table 3

Table 4

[0033] Stability test for storage life RP-HPLC: This procedure is a gradient reverse phase HPLC method with UV detection at 214 nm and is designed to determine the amount, identity, and purity of thilzepide in a drug product. Identity is determined by matching the retention time of the main peak in the sample with the retention time of the main peak of an external reference standard. The amount is determined by comparison of the main peak area with the corresponding peak in the external reference standard. Impurities and related substances are reported as peak area percentages relative to the total area. The procedure demonstrates stability as judged by its ability to degrade known impurities from thilzepide. As shown by Table 4, compositions containing NaCl as an isotonic agent provide acceptable stability during use.

[0034] Stability test for storage life of size exclusion chromatography (SEC)​​​​​​​​​​​​ The size exclusion stability test method and RP-HPLC described in this specification are applied to compare a composition containing NaCl as an isotonic agent and a stabilizer with a composition containing propylene glycol as an isotonic agent and a stabilizer. This test exemplifies the acceptable shelf life stability of the composition of the present invention containing an NaCl agent or containing propylene glycol as a drug. The compositions used in this test are described in Table 5. The stability from this test is shown in Table 6.

Table 5

Table 6

[0035] Post-injection pain test: All compositions are prepared as described in Table 7. Each solution composition vial is held at room temperature for about 30 minutes, but for 4 hours or less. The lyophilized composition is reconstituted and used immediately. All injections are rotated among the four quadrants of the abdomen in the following order: lower left quadrant, lower right quadrant, upper left quadrant, and upper right quadrant. A syringe with a 29-gauge needle is used to administer the composition from the vial. The skin fold at the injection site is pinched by the subject, and the needle is inserted at an angle of about 45 degrees. A second person uses a stopwatch to measure the length of the injection time. The subject slowly pushes the plunger of the syringe until 0.5 mL of the composition is injected. The target injection time is a duration of 4 seconds and is 5 seconds or less. The needle is removed from the skin after injection, and the skin is released from the subject's pinch. The subject evaluates the pain immediately after each injection. Pain The measurement is evaluated using a 100 mm validated visual analogue scale (VAS) for pain . The VAS is a well - validated tool for assessing pain at the injection site (Willi amson, A.; Hoggart, B. Pain: A review of thre e commonly used pain rating scales. Journ al of Clinical Nursing 2005, 14, (7), 798 - 8 04). The VAS is presented as a 10 cm (100 mm) line fixed by verbal descriptors, usually "no pain" and "worst imaginable pain" . Subjects are asked to mark the 100 mm line to indicate the pain intensity as clinically demonstrated at the time point. Staff members use calipers to measure the distance from the zero point to the mark placed by the subject on the VAS and record the measurement in the source document. The results from this test are shown in Table 8. The acceptable patient experience at the injection site is reflected by an indicator of mild pain intensity (compared to moderate or severe).

Table 7

Table 8

Table 9

Table 10

[0036] Array SEQ ID NO: 1 Tilsepaptide YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPP​​​ S In the formula, X1 is Aib, X2 is Aib, and the K at the 20th position is (2-[2-( 2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2 )18-CO2H is chemically modified through binding to the epsilon-amino group of the K side chain, and the C-terminal amino acid is amidated as a C-terminal primary amide.

Claims

1. Tilsupatiide, or a pharmaceutically acceptable salt thereof, and a drug selected from the group consisting of NaCl and propylene glycol, sodium dibasic phosphate, a pharmaceutical composition comprising the same.

2. The concentration of the tilsupatiide, or a pharmaceutically acceptable salt thereof, is about 5 to about 30 mg / m L, the pharmaceutical composition according to claim 1.

3. The sodium dibasic phosphate concentration is about 1.0 mg / mL to about 3.0 mg / mL The pharmaceutical composition according to claim 2.

4. The sodium dibasic phosphate concentration is about 0.67 mg / mL to about 2.68 mg / mL The pharmaceutical composition according to claim 3.

5. The sodium dibasic phosphate concentration is about 1.34 mg / mL, the pharmaceutical composition according to claim 4 of.

6. The concentration of the tilsupatiide, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of 5, 10, 15, 20 , 25, and 30 mg / mL, the pharmaceutical composition according to claim 1. composition.

7. The concentration of the tilsupatiide, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of 10, 20, and 3 0 mg / mL, the pharmaceutical composition according to claim 6.

8. The drug is NaCl, the pharmaceutical composition according to claim 7.

9. The concentration of the NaCl is about 6.2 mg / mL to about 9.5 mg / mL, according to claim 8 The pharmaceutical composition described.

10. The concentration of the NaCl is about 7.0 mg / mL to about 9.0 mg / mL, according to claim 9 The pharmaceutical composition described.

11. The NaCl concentration is about 8.2 mg / mL, the pharmaceutical composition according to claim 10.

12. The concentration of tilsupatiide, or a pharmaceutically acceptable salt thereof, is about 5 mg / mL to about 30 m g / mL, the sodium dibasic phosphate concentration is about 0.67 mg / mL to about 2.68 mg / mL, and the NaCl concentration is about 6.2 mg / mL to about 9.5 mg / mL, The pharmaceutical composition according to claim 1.

13. The concentration of tilsupatiide, or a pharmaceutically acceptable salt thereof, is about 5 mg / mL to about 30 m g / mL, the sodium dibasic phosphate concentration is about 1.34 mg / mL, and Na The Cl concentration is about 8.2 mg / mL, the pharmaceutical composition according to claim 12.

14. The composition is provided in an auto-injector device, the pharmaceutical composition according to claim 13.

15. The pharmaceutical composition according to claim 1, wherein the agent is propylene glycol.

16. The pharmaceutical composition according to claim 15, wherein the concentration of the propylene glycol is from about 12.0 mg / mL to about 18.0 mg / mL. The pharmaceutical composition according to claim 15, wherein the concentration of the propylene glycol is from about 12.0 mg / mL to about 18.0 mg / mL.

17. The pharmaceutical composition according to claim 16, wherein the concentration of the propylene glycol is from about 14.0 mg / mL to about 16.0 mg / mL. The pharmaceutical composition according to claim 16, wherein the concentration of the propylene glycol is from about 14.0 mg / mL to about 16.0 mg / mL.

18. The pharmaceutical composition according to claim 17, wherein the concentration of the propylene glycol is about 15.0 mg / mL. The pharmaceutical composition according to claim 17, wherein the concentration of the propylene glycol is about 15.0 mg / mL.

19. The concentration of tildipirosin, or a pharmaceutically acceptable salt thereof, is from about 5 mg / mL to about 30 mg / mL, the concentration of dibasic sodium phosphate is from about 0.67 mg / mL to about 2.68 mg / mL, and the concentration of propylene glycol is from about 14.0 mg / mL to about 16.0 mg / mL. The concentration of tildipirosin, or a pharmaceutically acceptable salt thereof, is from about 5 mg / mL to about 30 mg / mL, the concentration of dibasic sodium phosphate is from about 0.67 mg / mL to about 2.68 mg / mL, and the concentration of propylene glycol is from about 14.0 mg / mL to about 16.0 mg / mL. The pharmaceutical composition according to claim 1, wherein the concentration of tildipirosin, or a pharmaceutically acceptable salt thereof, is from about 5 mg / mL to about 30 mg / mL, the concentration of dibasic sodium phosphate is from about 0.67 mg / mL to about 2.68 mg / mL, and the concentration of propylene glycol is from about 14.0 mg / mL to about 16.0 mg / mL. The pharmaceutical composition according to claim 1, wherein the concentration of tildipirosin, or a pharmaceutically acceptable salt thereof, is from about 5 mg / mL to about 30 mg / mL, the concentration of dibasic sodium phosphate is from about 0.67 mg / mL to about 2.68 mg / mL, and the concentration of propylene glycol is from about 14.0 mg / mL to about 16.0 mg / mL.

20. The concentration of tildipirosin, or a pharmaceutically acceptable salt thereof, is from about 5 mg / mL to about 30 mg / mL, the concentration of dibasic sodium phosphate is about 1.34 mg / mL, and the concentration of propylene glycol is about 15.0 mg / mL. The concentration of tildipirosin, or a pharmaceutically acceptable salt thereof, is from about 5 mg / mL to about 30 mg / mL, the concentration of dibasic sodium phosphate is about 1.34 mg / mL, and the concentration of propylene glycol is about 15.0 mg / mL. The pharmaceutical composition according to claim 19, wherein the concentration of tildipirosin, or a pharmaceutically acceptable salt thereof, is from about 5 mg / mL to about 30 mg / mL, the concentration of dibasic sodium phosphate is about 1.34 mg / mL, and the concentration of propylene glycol is about 15.0 mg / mL. The pharmaceutical composition according to claim 19, wherein the concentration of tildipirosin, or a pharmaceutically acceptable salt thereof, is from about 5 mg / mL to about 30 mg / mL, the concentration of dibasic sodium phosphate is about 1.34 mg / mL, and the concentration of propylene glycol is about 15.0 mg / mL.

21. The pharmaceutical composition according to claim 20, wherein the composition is provided in an auto-injector device.

22. The pharmaceutical composition according to claim 21, wherein the pH of the composition is from about 6.5 to about 7.

5.

23. The pharmaceutical composition according to claim 22, wherein the pH is from about 6.7 to about 7.

3.

24. The pharmaceutical composition according to claim 23, further comprising one or more preservatives.

25. The pharmaceutical composition according to claim 24, further comprising a preservative selected from the group consisting of metacresol and phenol. The pharmaceutical composition according to claim 24, further comprising a preservative selected from the group consisting of metacresol and phenol.

26. The pharmaceutical composition according to claim 25, wherein the preservative is metacresol.

27. The pharmaceutical composition according to claim 26, wherein the concentration of the metacresol is from about 2.0 mg / mL to about 4.0 mg / mL. The pharmaceutical composition according to claim 26, wherein the concentration of the metacresol is from about 2.0 mg / mL to about 4.0 mg / mL.

28. The pharmaceutical composition according to claim 27, wherein the concentration of the metacresol is about 3.15 mg / mL. The pharmaceutical composition according to claim 27, wherein the concentration of the metacresol is about 3.15 mg / mL.

29. The pharmaceutical composition according to claim 25, wherein the preservative is phenol.

30. The pharmaceutical composition according to claim 29, wherein the concentration of the phenol is from about 3.0 mg / mL to about 7.0 mg / mL. The pharmaceutical composition according to claim 29, wherein the concentration of the phenol is from about 3.0 mg / mL to about 7.0 mg / mL.

31. The pharmaceutical composition according to claim 30, wherein the phenol concentration is about 5.0 mg / mL 。

32. The concentration of tildepazide, or a pharmaceutically acceptable salt thereof, is from about 5 mg / mL to about 30 m g / mL, dibasic sodium phosphate is from about 0.67 to about 2.68 mg / mL, propylene glycol is from about 12.0 mg / mL to about 15.0 mg / mL, and further contains about 2.0 mg / mL to about 4.0 mg / mL of metacresol, the pharmaceutical composition according to claim 1.

33. The concentration of tildepazide, or a pharmaceutically acceptable salt thereof, is from about 5 mg / mL to about 30 m g / mL, dibasic sodium phosphate is from about 0.67 to about 2.68 mg / mL, propylene glycol is from about 12.0 mg / mL to about 18.0 mg / mL, and further contains about 3.0 mg / mL to about 7.0 mg / mL of phenol, the pharmaceutical composition according to claim 1.

34. The pharmaceutical composition according to claim 33, wherein the volume of the composition dosage is about 0.5 mL.

35. The pharmaceutical composition according to claim 34, wherein the composition is administered using an auto-injector device 。

36. A method for treating diabetes, comprising administering to a human in need thereof an effective dose of the pharmaceutical composition according to claim 33.

37. The method for treating diabetes according to claim 36, wherein the dose is administered using an auto-injector device.

38. The method for treating diabetes according to claim 37, wherein the dose is administered once a week.

39. A method for treating obesity, comprising administering to a human in need thereof an effective dose of the pharmaceutical composition according to claim 33.

40. The method for treating obesity according to claim 39, wherein the dose is administered using an auto-injector device.

41. The method for treating obesity according to claim 40, wherein the dose is administered once a week.

42. The pharmaceutical composition according to claim 33 for use in the treatment of diabetes.

43. The pharmaceutical composition according to claim 33 for use in the treatment of obesity.

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