Formulations for personalized methods of treatment

Abstract

The present application relates to formulations for individualized methods of treatment. Disclosed herein are formulations and methods of administering formulations to lack cells with nutrients, such as amino acids. The formulations of the present invention may be substantially free of one or more non-essential amino acids. Disclosed herein is a composition comprising in unit dosage forms: a) a non-essential amino acid or a salt thereof wherein the non-essential amino acid or the salt thereof is not part of a polypeptide; b) a first essential amino acid or a first salt thereof and a second essential amino acid or a second salt thereof wherein the first essential amino acid or the first salt thereof and the second essential amino acid or the second salt thereof are present in the composition in an equal amount, wherein the first essential amino acid and the first salt thereof and the second essential amino acid and the second salt thereof are not part of a polypeptide; and c) a pharmaceutically acceptable excipient.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202511487589.7 (22) Application Date 2021.06.02 (30) Priority Data 63 / 034,137 2020.06.03 US (62) Divisional Application Data 202180057236.7 2021.06.02 (71) Applicant: Faith Therapeutics, Inc. Address: Texas, USA (72) Inventor: Oliver D.K. Maddox (74) Patent Agency: Beijing Anxin Fangda Intellectual Property Agency Co., Ltd. 11262 Patent Attorneys: Wei Changjin, Zheng Xia (51) Int.Cl. A61K 31 / 198 (2006.01) A61K 31 / 4172 (2006.01) A61K 45 / 06 (2006.01) A61P 35 / 00 (2006.01) A23L 33 / 15 (2016.01) A23L 33 / 175 (2016.01) (54) Title of Invention: Formulation for Personalized Treatment Methods (57) Abstract This application relates to formulations for personalized treatment methods. Formulations and methods of administering the formulations to deprive cells of nutrients such as amino acids are disclosed herein. The formulations of this invention may substantially be free of one or more non-essential amino acids. This document discloses a composition comprising, in unit dosage form: a) a non-essential amino acid or a salt thereof, wherein the non-essential amino acid or its salt is not part of a polypeptide; b) a first essential amino acid or a first salt thereof and a second essential amino acid or a second salt thereof, wherein the first essential amino acid or its first salt and the second essential amino acid or its second salt are present in equal amounts in the composition, wherein the first essential amino acid and its first salt and the second essential amino acid and its second salt are not part of a polypeptide; and c) a pharmaceutically acceptable excipient. Claims 1 page, Description 87 pages, Drawings 13 pages, CN 121445725 A 2026.02.03 CN 1 21 44 57 25 A 1. A composition comprising, in unit dosage form: a) a non-essential amino acid or a salt thereof, wherein said non-essential amino acid or said salt thereof is not part of a polypeptide; b) a first essential amino acid or a first salt thereof and a second essential amino acid or a second salt thereof, wherein said first essential amino acid or said first salt thereof and second essential amino acid or said second salt thereof are present in the composition in equal amounts, wherein said first essential amino acid and said first salt thereof and second essential amino acid and said second salt thereof are not part of a polypeptide; and c) a pharmaceutically acceptable excipient.2. The composition of claim 1, wherein the first essential amino acid or its first salt is histidine, and the second essential amino acid or its second salt is isoleucine. 3. The composition of claim 1, wherein the first essential amino acid and the second essential amino acid are present in the composition in an amount of about 2% to about 6% (w / w). 4. The composition of claim 1, further comprising a third essential amino acid, wherein the third essential amino acid is present in the composition in an amount different from that of the first essential amino acid and the second essential amino acid. 5. The composition of claim 1, wherein the composition does not contain at least one non-essential amino acid. 6. The composition of claim 1, wherein the composition does not contain at least serine and glycine. 7. The composition of claim 1, wherein the composition does not contain at least proline. 8. The composition of claim 1, wherein the composition does not contain at least cysteine. 9. The composition of claim 1, wherein the weight of the unit dosage form is about 12 grams. 10. The composition of claim 1, wherein the composition is in powder form. Claims 1 / 1 Page 2 CN 121445725 A Formulation for Personalized Treatment Methods

[0001] This application is a divisional application of application filed on June 2, 2021, application number 202180057236.7, entitled "Formulation for Personalized Treatment Methods".

[0002] Cross-Reference This application claims the benefit of U.S. Provisional Application No. 63 / 034,137, filed on June 3, 2020, which is incorporated herein by reference in its entirety. Background Art

[0003] Current therapies for treating cancer or other pathologies may be ineffective due to patient-specific factors. Therefore, personalized methods and formulations can be developed to achieve treatment for a variety of diseases, including cancer.

[0004] All publications, patents, and patent applications referenced in this specification are incorporated herein by reference to the extent that each individual publication, patent, or patent application is specifically and individually indicated to be incorporated by reference.

[0005] In some embodiments, this invention discloses a composition comprising, in unit dosage form: a) a non-essential amino acid or a salt thereof, wherein said non-essential amino acid or said salt thereof is not part of a polypeptide; b) a first essential amino acid or a first salt thereof and a second essential amino acid or a second salt thereof, wherein said first essential amino acid or said first salt thereof and second essential amino acid or said second salt thereof are present in the composition in equal amounts, wherein said first essential amino acid and said first salt thereof and second essential amino acid and said second salt thereof are not polypeptides.The composition comprises, in powder form: a) an essential amino acid, wherein the essential amino acid is not part of the polypeptide; b) a non-essential amino acid, wherein the non-essential amino acid is not part of the polypeptide; and c) a pharmaceutically acceptable excipient, wherein the composition does not contain serine or glycine, wherein, in a study of changes in tumor volume of a subject, the tumor volume of a subject treated with the composition is reduced by at least about 20% compared to a subject not treated with the composition.

[0006] In some embodiments, a composition is disclosed herein comprising, in unit dosage form: a) a non-essential amino acid or a salt thereof, wherein said non-essential amino acid or said salt thereof is not part of a polypeptide; b) a first essential amino acid or a first salt thereof and a second essential amino acid or a second salt thereof, wherein said first essential amino acid or said first salt thereof and the second essential amino acid or said second salt thereof are present in the composition in equal amounts, wherein said first essential amino acid and said first salt thereof and the second essential amino acid and said second salt thereof are not part of a polypeptide; and c) a pharmaceutically acceptable excipient, wherein, if in a study of changes in tumor volume of a subject, the tumor volume of a subject administering the composition is reduced by at least about 20% compared to a subject administering a placebo.

[0007] In some embodiments, a composition is disclosed herein in powder form comprising: a) an essential amino acid, wherein the essential amino acid is not part of a polypeptide; b) a non-essential amino acid, wherein the non-essential amino acid is not part of a polypeptide; and c) a pharmaceutically acceptable excipient, wherein the composition does not contain serine or glycine, and wherein, in a study of changes in tumor volume in a subject, the tumor volume of a subject administered the composition is reduced by at least about 20% compared to a subject administered a placebo. In some embodiments, a method for reducing tumor volume in a subject is disclosed herein, the method comprising administering to the subject a therapeutically effective amount of a composition, wherein the composition does not contain at least one non-essential amino acid, for at least one month.

[0008] In some embodiments, a method for treating cancer in a subject in need is disclosed herein, wherein the subject receives a modified diet, wherein the modified diet provides up to about 50% of daily calories from carbohydrates, the method comprising administering to the subject a therapeutically effective amount of a dietary product, wherein the dietary product does not contain at least one non-essential amino acid. In some embodiments, this document discloses a method for reducing the mean serum amino acid level of at least one non-essential amino acid in a subject in need, the method comprising: a) administering a treatment-effective amino acid to the subject.The subject receives a dietary product that does not contain the at least one non-essential amino acid for a first time period; wherein the subject receives a modified diet during the first time period, the modified diet providing at least about 1% to at most about 40% of daily calories from carbohydrates; and b) the dietary product is not administered to the subject for a second time period, wherein the subject receives a normal diet during the second time period, the normal diet providing at least about 45% of daily calories from carbohydrates.

[0009] This application provides the following: 1. A composition comprising, in unit dosage form: a) a non-essential amino acid or a salt thereof, wherein the non-essential amino acid or its salt is not part of a polypeptide; b) a first essential amino acid or its first salt and a second essential amino acid or its second salt, wherein the first essential amino acid or its first salt and the second essential amino acid or its second salt are present in equal amounts in the composition, wherein the first essential amino acid and its first salt and the second essential amino acid and its second salt are not part of a polypeptide; and c) a pharmaceutically acceptable excipient.

[0010] 2. The composition according to embodiment 1, wherein the first essential amino acid or its first salt is histidine, and the second essential amino acid or its second salt is isoleucine.

[0011] 3. The composition according to embodiment 1, wherein the first essential amino acid and the second essential amino acid are present in the composition in an amount of about 2% to about 6% (w / w).

[0012] 4. The composition according to embodiment 1, further comprising a third essential amino acid, wherein the third essential amino acid is present in the composition in an amount different from that of the first essential amino acid and the second essential amino acid.

[0013] 5. The composition according to embodiment 1, wherein the composition does not contain at least one non-essential amino acid.

[0014] 6. The composition according to embodiment 1, wherein the composition does not contain at least serine and glycine.

[0015] 7. The composition according to embodiment 1, wherein the composition does not contain at least proline.

[0016] 8. The composition according to embodiment 1, wherein the composition does not contain at least cysteine.

[0017] 9. The composition according to embodiment 1, wherein the weight of the unit dosage form is about 12 grams.

[0018] 10. The composition according to embodiment 1, wherein the composition is in powder form.

[0019] 11. The composition according to embodiment 1, wherein the composition further comprises about 2% to about 5% of a K+ source.

[0020] 12. The composition according to embodiment 1, wherein the K+ source includes potassium citrate, potassium phosphate, potassium chloride, potassium sulfate, potassium gluconate, potassium bicarbonate, potassium aspartate, potassium acetate, and potassium orotate.

[0021] 13. The composition according to embodiment 1, wherein the composition further comprises about 1% to about 4% (w / w) of a Mg2+ source.

[0022] 14. The composition according to embodiment 1, wherein the Mg2+ source comprises magnesium citrate, magnesium fumarate, magnesium ethoxylate, magnesium aspartate, magnesium threonate, magnesium glycine, magnesium chloride, magnesium sulfate, magnesium oxide, or magnesium malate, magnesium orotate, or their hydrates.

[0023] 15. The composition according to embodiment 1, wherein the composition further comprises about 0.05% to about 2% (w / w) of taurine, its hydrate, or salts thereof.

[0024] 16. A method of treating cancer in a subject in need, wherein the subject receives a modified diet, wherein the modified diet provides up to about 50% of daily calories from carbohydrates, the method comprising administering to the subject a therapeutically effective amount of a dietary product, wherein the dietary product does not contain at least one non-essential amino acid.

[0025] 17. The method according to embodiment 16, wherein the administration is oral.

[0026] 18. The method according to embodiment 16, wherein the modified diet provides up to about 15% of the daily calories from carbohydrates.

[0027] 19. The method according to embodiment 16, wherein the modified diet provides at least about 50% of the daily calories from fat.

[0028] 20. The method according to embodiment 16, wherein the therapeutically effective dose is about 0.5 g / kg / day to about 1 g / kg / day.

[0029] 21. The method according to embodiment 20, wherein the therapeutically effective dose is about 0.8 g / kg / day.

[0030] 22. The method according to embodiment 16, wherein the dietary product is free of at least serine and glycine.

[0031] 23. The method according to embodiment 16, wherein the dietary product is free of at least one of proline, tyrosine, cysteine, or arginine.

[0032] 24. According to embodiment 16, the application reduces the tumor volume of the subject by at least about 20% compared to a subject not treated with the composition.

[0033] 25. According to embodiment 16, the cancer is pancreatic cancer.

[0034] 26. According to embodiment 16, the cancer is colorectal cancer.

[0035] 27. According to embodiment 16, the method further includes the application of a therapeutic agent.

[0036] 28. According to embodiment 27, the therapeutic agent is a chemotherapeutic agent.

[0037] 29. According to embodiment 27, the therapeutic agent is a radiotherapy agent.

[0038] 30. A method for reducing the mean serum amino acid level of at least one non-essential amino acid in a subject in need, the method comprising: a) administering to the subject a therapeutically effective amount of a dietary product excluding the at least one non-essential amino acid for a first time period; wherein the subject receives a modified diet during the first time period, the modified diet providing at least about 1% to at most about 40% of daily calories from carbohydrates; and b) not administering the dietary product to the subject for a second time period, wherein the subject receives a normal diet during the second time period, the normal diet providing at least about 45% of daily calories from carbohydrates.

[0039] 31. The method according to embodiment 30, wherein the first time period is about 5 days.

[0040] 32. The method according to embodiment 30, wherein the second time period is about 2 days.

[0041] 33. The method according to embodiment 30, further comprising cycling steps a) and b).

[0042] 34. The method according to embodiment 33, comprising cycling steps a) and b) for at least about 1 week.

[0043] 35. According to the method of embodiment 30, wherein the mean serum amino acid level is reduced by at least about 30%.

[0044] 36. According to the method of embodiment 30, wherein the reduced mean serum amino acid level persists during the second time period. Specification 3 / 87 pages 5 CN 121445725 A

[0045] 37. According to the method of embodiment 30, wherein the modified diet provides at least about 50% of the daily calories from fat.

[0046] 38. According to the method of embodiment 30, wherein the therapeutically effective amount is about 0.5 g / kg / day to about 1 g / kg / day.

[0047] 39. According to the method of embodiment 30, wherein the dietary product is free from at least serine and glycine.

[0048] 40. According to the method of embodiment 30, wherein the dietary product is free from at least one of proline, tyrosine, cysteine, or arginine.

[0049] 41. According to the method of embodiment 30, further comprising administering a therapeutic agent.

[0050] 42. According to the method of embodiment 41, wherein the therapeutic agent is a chemotherapeutic agent.

[0051] 43. The method according to embodiment 41, wherein the therapeutic agent is a radiotherapy agent. Brief Description of the Drawings

[0052] Figure 1 illustrates the addition of a sachet containing the composition disclosed herein to a glass of water, and the subject drinking the mixture of the composition.

[0053] Figure 2 provides a graph showing the serum amino acid levels of the subject before and after administration of a proline-deficient diet as described in Example 17.

[0054] Figure 3 provides a graph showing the serum amino acid levels of subjects before and after administration of a proline-deficient diet as described in Example 18.

[0055] Figure 4 provides a graph showing the serum amino acid levels of subjects before and after administration of a proline-deficient diet as described in Example 19.

[0056] Figure 5 provides a graph showing the serum proline levels as a percentage of pre-diet baseline levels for subjects administered a proline-deficient diet as described in Examples 17(A), 18(B), and 19(C).

[0057] Figure 6 is a graph showing the serum proline levels as a percentage of pre-diet baseline levels in pancreatic cancer patients administered a proline-deficient diet as described in Example 20.

[0058] Figure 7 provides a graph showing the serum amino acid levels of subjects before and after administration of a serine and glycine-deficient diet as described in Example 21.

[0059] Figure 8 provides a graph showing the serum amino acid levels of subjects before and after administration of a proline, glycine, and serine-deficient diet as described in Example 22.

[0060] Figure 9 provides a graph showing the serum serine, proline, and glycine levels as a percentage of pre-diet baseline levels for subjects who were given the diet described in Example 22.

[0061] Figure 10 provides a graph showing the serum proline, glycine, and serine levels for subjects who were given a diet lacking serine, proline, and glycine daily (A) or intermittently (B) according to the protocol described in Example 23. C (left) shows a graph of serum amino acids as a percentage of the habitual diet for subjects who were given a diet lacking serine, glycine, or proline daily or intermittently for 11 consecutive days. C (right) shows a graph of serum amino acids as a percentage of the habitual diet for subjects who were given a diet lacking serine, glycine, or proline intermittently for 16 consecutive days or intermittently for 18 consecutive days.

[0062] Figure 11 provides a graph showing the serum amino acid levels of subjects after being given a low-protein diet lacking serine, glycine, glutamate, and cysteine ​​at 1613 kcal / day, as described in Example 24.

[0063] Figure 12 provides a graph showing the serum amino acid levels of subjects after administration of a low-protein, low-carbohydrate diet lacking serine, glycine, glutamic acid, and cysteine, as described in Example 24.

[0064] Figure 13 provides a graph showing the serum amino acid levels of subjects before and after administration of a low-protein diet (A) of 1613 kcal / day or a low-protein, low-carbohydrate diet (B) as described in Example 24. Figure 13 shows the mean % serum level after administration of the low-protein diet (left) and the mean % serum level after administration of the low-protein, low-carbohydrate diet (right).Detailed Description

[0065] This document describes compositions and dietary products containing essential and non-essential amino acids. The compositions disclosed herein may be administered to a subject to treat a disease, such as cancer. As shown in FIG1, the compositions disclosed herein may be provided as powder in a capsule (101). The powder from the capsule may be added to, for example, water (102) to produce a liquid beverage for the subject to consume. The subject (104) drinks a mixture of compositions prepared in water (103).

[0066] Removing specific amino acids or combinations of amino acids from a subject's diet may improve the treatment of a variety of diseases, including cancer. The reduction in the subject's amino acid levels reduces the production of proteins, metabolites, lipids, or nucleic acids that may promote cancer growth and metastasis.

[0067] In some embodiments, the compositions disclosed herein are pharmaceutical compositions. In some embodiments, the compositions disclosed herein are medical foods. In some embodiments, the compositions disclosed herein are food supplements. In some embodiments, the compositions disclosed herein are nutritional supplements. In some embodiments, the compositions disclosed herein are nutrient supplements. In some embodiments, the compositions disclosed herein are dietary products. In some embodiments, the compositions disclosed herein are pharmaceuticals.

[0068] In some embodiments, the compositions disclosed herein can be used in conjunction with at least one therapeutic agent such as a drug, antibody, or enzyme. In some embodiments, the compositions disclosed herein can make the therapeutic agent more effective in treating a condition.

[0069] In some embodiments, the compositions disclosed herein are foods formulated for consumption or enteral administration under the supervision of a physician and intended for specific dietary management of a disease or condition for which unique nutritional needs based on recognized scientific principles have been determined through medical evaluation.

[0070] Amino Acids The compositions of this disclosure contain at least ten amino acids or salts thereof. In some embodiments, the compositions of this disclosure contain 10, 11, 12, 13, 14, 15, 16, 17, 18, or 19 amino acids or salts thereof. In some embodiments, the compositions of this disclosure contain 10 amino acids or salts thereof. In some embodiments, the compositions of this disclosure contain 14 amino acids or salts thereof. In some embodiments, the compositions of this disclosure comprise 18 amino acids or salts of any amino acid thereof. The salts of the amino acids disclosed herein may be pharmaceutically acceptable salts.

[0071] In some embodiments, the compositions of this disclosure comprise 1, 2, 3, 4, 5, 6, 7, 8, or 9 essential amino acids or salts of any amino acid thereof. In some embodiments, the compositions of this disclosure comprise 7, 8, or 9 essential amino acids.Salts of any of the amino acids thereof. In some embodiments, the compositions of this disclosure comprise 8 essential amino acids or salts of any of the amino acids thereof. In some embodiments, the compositions of this disclosure comprise 9 essential amino acids or salts of any of the amino acids thereof. The salts of the amino acids disclosed herein may be pharmaceutically acceptable salts.

[0072] In some embodiments, the compositions of this disclosure comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 non-essential amino acids or salts of any of the amino acids thereof. In some embodiments, the compositions of this disclosure comprise 7, 8, 9, 10 or 11 non-essential amino acids or salts of any of the amino acids thereof. In some embodiments, the compositions of this disclosure comprise 7 non-essential amino acids or salts of any of the amino acids thereof. In some embodiments, the compositions of this disclosure comprise 8 non-essential amino acids or salts of any of the amino acids thereof. In some embodiments, the compositions of this disclosure comprise 9 non-essential amino acids or salts of any of the amino acids thereof. The salts of the amino acids disclosed herein may be pharmaceutically acceptable salts.

[0073] The compositions of this disclosure may comprise essential amino acids or their salts, and non-essential amino acids or their salts. In some embodiments, the compositions of this disclosure comprise 1, 2, 3, 4, 5, 6, 7, 8, or 9 essential amino acids or their salts and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 non-essential amino acids or their salts. In some embodiments, the compositions of this disclosure comprise 7, 8, or 9 essential amino acids or their salts and 6, 7, 8, or 9 non-essential amino acids or their salts. In some embodiments, the compositions of this disclosure comprise 8 or 9 essential amino acids or their salts and 8 or 9 non-essential amino acids or their salts. In some embodiments, the compositions of this disclosure comprise 9 essential amino acids or their salts and 7 non-essential amino acids or their salts. In some embodiments, the compositions of this disclosure comprise 9 essential amino acids or their salts and 8 non-essential amino acids or their salts. In some embodiments, the compositions of this disclosure comprise nine essential amino acids or salts of any of those amino acids and nine non-essential amino acids or salts of any of those amino acids. The salts of the amino acids disclosed herein may be pharmaceutically acceptable salts.

[0074] In some embodiments, the compositions of this disclosure comprise histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, taurine, threonine, tryptophan, valine, arginine, glutamine, alanine, aspartic acid, asparagine, glutamic acid, or proline. In some embodiments, the compositions of this disclosure...The composition comprises L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-cysteine, L-phenylalanine, L-tyrosine, L-threonine, L-tryptophan, L-valine, L-arginine, L-glutamine, L-alanine, L-aspartic acid, L-asparagine, L-glutamic acid, or L-proline. Any composition of this disclosure may contain cysteine ​​instead of cystine, or contain cystine instead of cysteine.

[0075] In some embodiments, the composition comprises histidine or a salt thereof, such as L-histidine or L-histidine hydrochloride. In some embodiments, the composition of this disclosure comprises isoleucine or a salt thereof, such as L-isoleucine, L-isoleucine methyl ester hydrochloride, or L-isoleucine ethyl ester hydrochloride. Salts of the amino acids disclosed herein may be pharmaceutically acceptable salts. In some embodiments, the compositions of this disclosure comprise leucine or a salt thereof, such as L-leucine, L-leucine methyl ester hydrochloride, or L-leucine ethyl ester hydrochloride. Salts of the amino acids disclosed herein may be pharmaceutically acceptable salts. In some embodiments, the compositions of this disclosure comprise lysine or a salt thereof, such as L-lysine, L-lysine hydrochloride, or L-lysine dihydrochloride. Salts of the amino acids disclosed herein may be pharmaceutically acceptable salts. In some embodiments, the compositions of this disclosure comprise methionine or a salt thereof, such as L-methionine, L-methionine methyl ester hydrochloride, or L-methionine hydrochloride. Salts of the amino acids disclosed herein may be pharmaceutically acceptable salts.

[0076] In some embodiments, the compositions of this disclosure comprise cysteine ​​or a salt thereof, such as L-cysteine, L-cysteine ​​hydrochloride, L-cysteine ​​methyl ester hydrochloride, or L-cysteine ​​ethyl ester hydrochloride. Any composition of this disclosure may comprise cysteine ​​instead of cystine, or cystine instead of cysteine. In some embodiments, the compositions disclose cystine or a salt thereof, such as L-cystine. Salts of the amino acids disclosed herein may be pharmaceutically acceptable salts. In some embodiments, the compositions of this disclosure contain phenylalanine or a salt thereof, such as L-phenylalanine, DL-phenylalanine, or L-phenylalanine methyl ester hydrochloride. In some embodiments, the compositions of this disclosure contain tyrosine or a salt thereof, such as L-tyrosine or L-tyrosine hydrochloride. In some embodiments, the compositions of this disclosure contain threonine or a salt thereof, such as L-threonine or L-threonine methyl ester hydrochloride. In some embodiments, the compositions of this disclosure contain L-tryptophan. In some embodiments, the compositions of this disclosure contain valine or a salt thereof, such as L-valine, L-valine methyl ester hydrochloride, or L-valine ethyl ester hydrochloride. Salts of the amino acids disclosed herein may be...Pharmaceutically acceptable salts.

[0077] In some embodiments, the compositions of this disclosure comprise arginine or a salt thereof, such as L-arginine or L-arginine hydrochloride. In some embodiments, the compositions of this disclosure comprise glutamine or a salt thereof, such as L-glutamine or L-glutamine hydrochloride. In some embodiments, the compositions of this disclosure comprise alanine or a salt thereof, such as L-alanine or β-alanine. In some embodiments, the compositions of this disclosure comprise aspartic acid or a salt thereof, such as L-aspartic acid, D-aspartic acid, potassium L-aspartic acid or potassium D-aspartic acid, L-aspartic acid hydrochloride or D-aspartic acid hydrochloride, magnesium L-aspartic acid or magnesium D-aspartic acid, or calcium L-aspartic acid or calcium D-aspartic acid. In some embodiments, the compositions of this disclosure comprise L-asparagine. In some embodiments, the compositions of this disclosure comprise glutamic acid or a salt thereof, such as L-glutamic acid or L-glutamic acid hydrochloride. In some embodiments, the compositions of this disclosure contain proline or a salt thereof, such as L-proline, L-proline hydrochloride, L-proline methyl ester hydrochloride, or L-proline ethyl ester hydrochloride. Salts of the amino acids disclosed herein may be pharmaceutically acceptable salts.

[0078] In some embodiments, the compositions of this disclosure do not contain proline, its hydrate, or a salt thereof. In some embodiments, the compositions of this disclosure do not contain serine, its hydrate, or a salt thereof. In some embodiments, the compositions of this disclosure do not contain glycine, its hydrate, or a salt thereof. In some embodiments, the compositions of this disclosure do not contain cysteine, its hydrate, or a salt thereof. In some embodiments, the compositions of this disclosure do not contain glutamine, its hydrate, or a salt thereof. In some embodiments, the compositions of this disclosure do not contain glutamic acid, its hydrate, or a salt thereof.

[0079] In some embodiments, the compositions of this disclosure do not contain (a) serine, its hydrate, or a salt thereof; and (b) glycine, its hydrate, or a salt thereof. In some embodiments, the compositions of this disclosure do not contain (a) serine, its hydrate or a salt thereof; (b) glycine, its hydrate or a salt thereof; and (c) proline, its hydrate or a salt thereof. In some embodiments, the compositions of this disclosure do not contain (a) serine, its hydrate or a salt thereof; (b) glycine, its hydrate or a salt thereof; and (c) cysteine, its hydrate or a salt thereof. In some embodiments, the compositions of this disclosure do not contain (a) serine, its hydrate or a salt thereof; (b) glycine, its hydrate or a salt thereof; (c) proline, its hydrate or a salt thereof; and (d) cysteine, its hydrate or a salt thereof. In some embodiments, the compositions of this disclosure do not contain (a) serine, its hydrate or a salt thereof.The composition comprises (a) serine, its hydrate or salt thereof; (b) glycine, its hydrate or salt thereof; (c) proline, its hydrate or salt thereof; and (d) arginine, its hydrate or salt thereof. In some embodiments, the composition of this disclosure does not contain (a) serine, its hydrate or salt thereof; (b) glycine, its hydrate or salt thereof; (c) proline, its hydrate or salt thereof; and (d) tyrosine, its hydrate or salt thereof. In some embodiments, the composition of this disclosure does not contain (a) serine, its hydrate or salt thereof; (b) glycine, its hydrate or salt thereof; (c) cysteine, its hydrate or salt thereof; and (d) arginine, its hydrate or salt thereof. In some embodiments, the composition of this disclosure does not contain (a) serine, its hydrate or salt thereof; (b) glycine, its hydrate or salt thereof; (c) cysteine, its hydrate or salt thereof; and (d) tyrosine, its hydrate or salt thereof.

[0080] In some embodiments, the compositions of this disclosure do not contain (a) serine, its hydrate or a salt thereof; (b) glycine, its hydrate or a salt thereof; (c) proline, its hydrate or a salt thereof; (d) cysteine, its hydrate or a salt thereof; and (e) arginine, its hydrate or a salt thereof. In some embodiments, the compositions of this disclosure do not contain (a) serine, its hydrate or a salt thereof; (b) glycine, its hydrate or a salt thereof; (c) proline, its hydrate or a salt thereof; (d) cysteine, its hydrate or a salt thereof; (e) tyrosine, its hydrate or a salt thereof; and (f) arginine, its hydrate or a salt thereof. In some embodiments, the compositions of this disclosure do not contain (a) serine, its hydrate or a salt thereof; (b) glycine, its hydrate or a salt thereof; (c) cysteine, its hydrate or a salt thereof; (d) glutamine, its hydrate or a salt thereof; and (e) glutamic acid, its salt, its hydrate or a salt thereof. In some embodiments, the compositions of this disclosure also do not contain glutamine, its hydrate or a salt thereof. In some embodiments, the compositions of this disclosure also do not contain glutamate, its hydrate or a salt thereof.

[0081] In some embodiments, the composition may comprise at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the following: a) about 2% to about 6% (w / w) of histidine or a salt thereof; b) about 2% to about 6% (w / w) of isoleucine or a salt thereof; c) about 6% to about 11% (w / w) of leucine or a salt thereof; d) about 5% to about 9% of...e) lysine or a salt thereof (w / w); e) about 2% to about 4% (w / w) methionine or a salt thereof; f) about 1% to about 3% (w / w) cysteine ​​or a salt thereof; g) about 3% to about 6% (w / w) phenylalanine or a salt thereof; h) about 1% to about 3% (w / w) tyrosine or a salt thereof; i) about 3% to about 5% (w / w) threonine or a salt thereof; j) about 1% to about 3% (w / w) tryptophan or a salt thereof; k) about 5% to about 9% (w / w) valine or a salt thereof; l) about 5% to about 9% (w / w) arginine or a salt thereof; m) about 5% to about 11% (w / w) glutamine or a salt thereof; n) about 2% to about 7% (w / w) alanine or a salt thereof; o) about 6% to about 10% (w / w) aspartic acid or a salt thereof; p) about 3% to about 7% (w / w) asparagine or a salt thereof; q) about 8% to about 14% (w / w) glutamic acid or a salt thereof; or r) about 6% to about 12% (w / w) proline or a salt thereof. In some embodiments, the composition may comprise, in unit dosage form: a) about 2% to about 6% (w / w) histidine or a salt thereof; b) about 2% to about 6% (w / w) isoleucine or a salt thereof; c) about 6% to about 11% (w / w) leucine or a salt thereof; d) about 5% to about 9% (w / w) lysine or a salt thereof; e) about 2% to about 4% (w / w) methionine or a salt thereof; f) about 1% to about 3% (w / w) cysteine ​​or a salt thereof; g) about 3% to about 6% (w / w) phenylalanine or a salt thereof; h) about 1% to about 3% (w / w) tyrosine or a salt thereof; i) about 3% to about 5% (w / w) threonine or a salt thereof; j) about 1% to about 3% (w / w) tryptophan or a salt thereof; k) about 5% to about 9% (w / w) valine or a salt thereof; l) about 5% to about 9% (w / w) arginine or a salt thereof; m) about 5% to about 11% (w / w) glutamine or a salt thereof; n) about 2% to about 7% (w / w) alanine or a salt thereof; o) about 6% to about 10% (w / w) aspartic acid or a salt thereof; p) about 3% to about 7% (w / w) asparagine or a salt thereof; q) about 8% to about 14% (w / w) glutamic acid or a salt thereof; and r) about 6% to about 12% (w / w) proline or a salt thereof. Any composition of this disclosure may contain cysteine ​​instead of cystine, or cystine instead of cysteine.

[0082] In some embodiments, the compositions of this disclosure may comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 of the following: a) about 5% to about 9% (w / w) of histidine or a salt thereof; b) about 5% to about 9% (w / w) of isoleucine or a salt thereof; c) about 9% to about 15% (w / w) of leucine or a salt thereof; d) about 7% to about 12% of...(w / w) lysine or a salt thereof; e) about 5% to about 8% (w / w) methionine or a salt thereof; f) about 4% to about 7% (w / w) cysteine ​​or a salt thereof; g) about 6% to about 10% (w / w) phenylalanine or a salt thereof; h) about 4% to about 7% (w / w) tyrosine or a salt thereof; i) about 6% to about 10% (w / w) threonine or a salt thereof; j) about 4% to about 7% (w / w) tryptophan or a salt thereof; k) about 8% to about 13% (w / w) valine or a salt thereof; l) about 5% to about 9% (w / w) arginine or a salt thereof; or m) about 7% to about 11% (w / w) glutamine or a salt thereof. In some embodiments, the composition may comprise, in unit dosage form: a) about 5% to about 9% (w / w) histidine or a salt thereof; b) about 5% to about 9% (w / w) isoleucine or a salt thereof; c) about 9% to about 15% (w / w) leucine or a salt thereof; d) about 7% to about 12% (w / w) lysine or a salt thereof; e) about 5% to about 8% (w / w) methionine or a salt thereof; f) about 4% to about 7% (w / w) cysteine ​​or a salt thereof; g) about 6% to about 10% (w / w) phenylalanine or a salt thereof; h) about 4% to about 7% (w / w) tyrosine or a salt thereof; i) about 6% to about 10% (w / w) threonine or a salt thereof; j) about 4% to about 7% (w / w) tryptophan or a salt thereof; k) about 8% to about 13% (w / w) valine or a salt thereof; l) about 5% to about 9% (w / w) arginine or a salt thereof; and (m) about 7% to about 11% (w / w) glutamine or a salt thereof. Any composition of this disclosure may contain cysteine ​​instead of cystine, or contain cystine instead of cysteine. Specification page 8 / 87 10 CN 121445725 A

[0083] In some embodiments, the composition may comprise at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 of the following: a) about 2% to about 5% (w / w) histidine or a salt thereof; b) about 2% to about 5% (w / w) isoleucine or a salt thereof; c) about 6% to about 10% (w / w) leucine or a salt thereof; d) about 5% to about 8% (w / w) lysine or a salt thereof; e) about 2% to about 4% (w / w) methionine or a salt thereof; f) about 1% to about 3% (w / w) cysteine ​​or a salt thereof; g) about 3% to about 5% (w / w) phenylalanine or a salt thereof; h) about 1% to about 3% (w / w) tyrosine or a salt thereof; i) about 3% to about 5% (w / w) lysine or a salt thereof; w) threonine or a salt thereof; j) about 1% to about 3% (w / w) tryptophan or a salt thereof; k) about 5% to about 9% (w / w) valine or a salt thereof; l) about 5% to about 9%(w / w) arginine or a salt thereof; m) about 7% to about 11% (w / w) glutamine or a salt thereof; n) about 4% to about 7% (w / w) alanine or a salt thereof; o) about 6% to about 10% (w / w) aspartic acid or a salt thereof; p) about 3% to about 6% (w / w) asparagine or a salt thereof; q) about 8% to about 14% (w / w) glutamic acid or a salt thereof; and r) about 6% to about 10% (w / w) proline or a salt thereof. In some embodiments, the composition may comprise, in unit dosage form: a) about 2% to about 5% (w / w) histidine or a salt thereof; b) about 2% to about 5% (w / w) isoleucine or a salt thereof; c) about 6% to about 10% (w / w) leucine or a salt thereof; d) about 5% to about 8% (w / w) lysine or a salt thereof; e) about 2% to about 4% (w / w) methionine or a salt thereof; f) about 1% to about 3% (w / w) cysteine ​​or a salt thereof; g) about 3% to about 5% (w / w) phenylalanine or a salt thereof; h) about 1% to about 3% (w / w) tyrosine or a salt thereof; i) about 3% to about 5% (w / w) threonine or a salt thereof; j) about 1% to about 3% (w / w) tryptophan or a salt thereof; k) about 5% to about 9% (w / w) valine or a salt thereof; l) about 5% to about 9% (w / w) arginine or a salt thereof; m) about 7% to about 11% (w / w) glutamine or a salt thereof; n) about 4% to about 7% (w / w) alanine or a salt thereof; o) about 6% to about 10% (w / w) aspartic acid or a salt thereof; p) about 3% to about 6% (w / w) asparagine or a salt thereof; q) about 8% to about 14% (w / w) glutamic acid or a salt thereof; and r) about 6% to about 10% (w / w) proline or a salt thereof. Any composition of this disclosure may contain cysteine ​​instead of cystine, or cystine instead of cysteine.

[0084] In some embodiments, the compositions of this disclosure may comprise at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 of the following: a) about 5% to about 9% (w / w) histidine or a salt thereof; b) about 5% to about 9% (w / w) isoleucine or a salt thereof; c) about 9% to about 15% (w / w) leucine or a salt thereof; d) about 7% to about 12% (w / w) lysine or a salt thereof; e) about 5% to about 8% (w / w) methionine or a salt thereof; f) about 4% to about 7% (w / w) cysteine ​​or a salt thereof; g) about 6% to about 10% (w / w) phenylalanine or a salt thereof; h) about 4% to about 7% (w / w) tyrosine or a salt thereof; i) about 6% to about 10% (w / w) threonine or a salt thereof; j) about 4% to about 7% (w / w) tryptophan or its salt; (k) about 8% to about 13% (w / w) valine or its salt; (l) about 5% to about 9%Arginine or its salt (w / w); or glutamine or its salt (m) of about 7% to about 11% (w / w). In some embodiments, the composition may comprise, in unit dosage form: a) about 5% to about 9% (w / w) histidine or a salt thereof; b) about 5% to about 9% (w / w) isoleucine or a salt thereof; c) about 9% to about 15% (w / w) leucine or a salt thereof; d) about 7% to about 12% (w / w) lysine or a salt thereof; e) about 5% to about 8% (w / w) methionine or a salt thereof; f) about 4% to about 7% (w / w) cysteine ​​or a salt thereof; g) about 6% to about 10% (w / w) phenylalanine or a salt thereof; h) about 4% to about 7% (w / w) tyrosine or a salt thereof; i) about 6% to about 10% (w / w) threonine or a salt thereof; j) about 4% to about 7% (w / w) tryptophan or a salt thereof; k) about 8% to about 13% (w / w) valine or a salt thereof; l) about 5% to about 9% (w / w) arginine or a salt thereof; and (m) about 7% to about 11% (w / w) glutamine or a salt thereof. Any composition of this disclosure may contain cysteine ​​instead of cystine, or contain cystine instead of cysteine.

[0085] In some embodiments, the composition may comprise at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the following: a) about 3% to about 7% (w / w) of histidine, its hydrate, or a salt thereof; b) about 3% to about 6% (w / w) of isoleucine, its hydrate, or a salt thereof; c) about 7% to about 11% (w / w) of leucine, its hydrate, or a salt thereof; d) about 5% to about 9% (w / w) of lysine, its hydrate, or a salt thereof; e) about 2% to about 4% (w / w) of methionine, its hydrate, or a salt thereof; f) about 1% to about 3% (w / w) of cysteine, its hydrate, or a salt thereof; g) about 3% to about 7% (w / w) of phenylalanine, its hydrate, or a salt thereof; (See page 9 / 87 of the specification, CN 121445725 A) h) about 1% to about 3% (w / w) of tyrosine, its hydrate or its salt; i) about 2% to about 5% (w / w) of threonine, its hydrate or its salt; j) about 1% to about 3% (w / w) of tryptophan, its hydrate or its salt; k) about 5% to about 9% (w / w) of valine, its hydrate or its salt; l) about 5% to about 9% (w / w) of arginine, its hydrate or its salt; m) about 7% to about 11% (w / w) of glutamine, its hydrate or its salt; n) about 3% to about 7% (w / w) of alanine, its hydrate or its salt; o) about 6% to about 10% (w / w) of aspartic acid, its hydrate or its salt; p) about 3% to about 6% (w / w) of asparagine, its hydrate or its salt; q) about 8% to about 14%(w / w) glutamic acid, its hydrate or salt thereof; (r) about 2% to about 5% (w / w) serine, its hydrate or salt thereof; or (s) about 3% to about 7% (w / w) glycine, its hydrate or salt thereof. In some embodiments, this document discloses a composition comprising, in unit dosage form: a) about 3% to about 7% (w / w) histidine, its hydrate or a salt thereof; b) about 3% to about 6% (w / w) isoleucine, its hydrate or a salt thereof; c) about 7% to about 11% (w / w) leucine, its hydrate or a salt thereof; d) about 5% to about 9% (w / w) lysine, its hydrate or a salt thereof; e) about 2% to about 4% (w / w) methionine, its hydrate or a salt thereof; f) about 1% to about 3% (w / w) cysteine, its hydrate or a salt thereof; g) about 3% to about 7% (w / w) phenylalanine, its hydrate or a salt thereof; h) about 1% to about 3% (w / w) tyrosine, its hydrate or a salt thereof; i) about 2% to about 5% (w / w) threonine, its hydrate or a salt thereof; j) about 1% to about 3% (w / w) tryptophan, ... The composition comprises: k) valine, hydrate, or salt thereof, at about 5% to about 9% (w / w); l) arginine, hydrate, or salt thereof, at about 5% to about 9% (w / w); m) glutamine, hydrate, or salt thereof, at about 7% to about 11% (w / w); n) alanine, hydrate, or salt thereof, at about 3% to about 7% (w / w); o) aspartic acid, hydrate, or salt thereof, at about 6% to about 10% (w / w); p) asparagine, hydrate, or salt thereof, at about 3% to about 6% (w / w); q) glutamic acid, hydrate, or salt thereof, at about 8% to about 14% (w / w); r) serine, hydrate, or salt thereof, at about 2% to about 5% (w / w); and s) glycine, hydrate, or salt thereof, at about 3% to about 7% (w / w). Any composition of this disclosure may contain cysteine ​​instead of cystine, or cystine instead of cysteine.

[0086] In some embodiments, the composition may comprise at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the following: a) about 3% to about 7% (w / w) of histidine, its hydrate, or a salt thereof; b) about 4% to about 8% (w / w) of isoleucine, its hydrate, or a salt thereof; c) about 9% to about 13% (w / w) of leucine, its hydrate, or a salt thereof; d) about 8% to about 12% (w / w) of lysine, its hydrate, or a salt thereof; e) about 1% to about 4% (w / w) of methionine, its hydrate, or a salt thereof; f) about 1% to about 4% (w / w) of cysteine, its hydrate, or a salt thereof; g) about 5% to about 9% (w / w) of phenylalanine, its hydrate, or a salt thereof; h) about 1% to about 5% of lysine.(w / w) tyrosine, its hydrate or salt thereof; i) about 4% to about 8% (w / w) threonine, its hydrate or salt thereof; j) about 1% to about 4% (w / w) tryptophan, its hydrate or salt thereof; k) about 5% to about 10% (w / w) valine, its hydrate or salt thereof; l) about 1% to about 10% (w / w) arginine, its hydrate or salt thereof; m) about 1% to about 5% (w / w) glutamine, its hydrate or salt thereof; n) about 4% to about 8% (w / w) alanine, its hydrate or salt thereof; o) about 4% to about 12% (w / w) aspartic acid, its hydrate, acid or salt thereof; p) about 4% to about 8% (w / w) asparagine, its hydrate or salt thereof; or q) about 5% to about 15% (w / w) glutamic acid, its hydrate or salt thereof. In some embodiments, the composition may comprise, in unit dosage form: a) about 3% to about 7% (w / w) histidine, its hydrate or a salt thereof; b) about 4% to about 8% (w / w) isoleucine, its hydrate or a salt thereof; c) about 9% to about 13% (w / w) leucine, its hydrate or a salt thereof; d) about 8% to about 12% (w / w) lysine, its hydrate or a salt thereof; e) about 1% to about 4% (w / w) methionine, its hydrate or a salt thereof; f) about 1% to about 4% (w / w) cysteine, its hydrate or a salt thereof; g) about 5% to about 9% (w / w) phenylalanine, its hydrate or a salt thereof; h) about 1% to about 5% (w / w) tyrosine, its hydrate or a salt thereof; i) about 4% to about 8% (w / w) threonine, its hydrate or a salt thereof; j) about 1% to about 4% k) about 5% to about 10% (w / w) of tryptophan, its hydrate or salt thereof; l) about 1% to about 10% (w / w) of arginine, its hydrate or salt thereof; m) about 1% to about 5% (w / w) of glutamine, its hydrate or salt thereof; n) about 4% to about 8% (w / w) of alanine, its hydrate or salt thereof; o) about 4% to about 12% (w / w) of aspartic acid, its hydrate, acid or salt thereof; p) about 4% to about 8% (w / w) of asparagine, its hydrate or salt thereof; and q) about 5% to about 15% (w / w) of glutamic acid, its hydrate or salt thereof. Any composition of this disclosure may contain cysteine ​​instead of cystine, or contain cystine instead of cysteine.

[0087] In some embodiments, the composition may comprise at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the following: a) about 4% to about 6% (w / w) of histidine, its hydrate, or a salt thereof; b) about 5% to about 7% (w / w) of...Isoleucine, its hydrate or salt thereof; c) about 9% to about 12% (w / w) of leucine, its hydrate or salt thereof; d) about 8% to about 12% (w / w) of lysine, its hydrate or salt thereof; e) about 1% to about 4% (w / w) of methionine, its hydrate or salt thereof; f) about 1% to about 3% (w / w) of cysteine, its hydrate or salt thereof; g) about 6% to about 8% (w / w) of phenylalanine, its hydrate or salt thereof; h) about 1% to about 4% (w / w) of tyrosine, its hydrate or salt thereof; i) about 4% to about 7% (w / w) of threonine, its hydrate or salt thereof; j) about 1% to about 3% (w / w) of tryptophan, its hydrate or salt thereof; k) about 4% to about 9% (w / w) of valine, its hydrate or salt thereof; l) about 7% to about 11% (w / w) arginine, its hydrate or salt thereof; m) about 2% to about 4% (w / w) glutamine, its hydrate or salt thereof; n) about 4% to about 7% (w / w) alanine, its hydrate or salt thereof; o) about 8% to about 11% (w / w) aspartic acid, its hydrate or salt thereof; p) about 4% to about 7% (w / w) asparagine, its hydrate or salt thereof; or q) about 4% to about 8% (w / w) glutamic acid, its hydrate or salt thereof. In some embodiments, the composition may comprise, in unit dosage form: a) about 4% to about 6% (w / w) histidine, its hydrate or a salt thereof; b) about 5% to about 7% (w / w) isoleucine, its hydrate or a salt thereof; c) about 9% to about 12% (w / w) leucine, its hydrate or a salt thereof; d) about 8% to about 12% (w / w) lysine, its hydrate or a salt thereof; e) about 1% to about 4% (w / w) methionine, its hydrate or a salt thereof; f) about 1% to about 3% (w / w) cysteine, its hydrate or a salt thereof; g) about 6% to about 8% (w / w) phenylalanine, its hydrate or a salt thereof; h) about 1% to about 4% (w / w) tyrosine, its hydrate or a salt thereof; i) about 4% to about 7% (w / w) threonine, its hydrate or a salt thereof; j) about 1% to about 3% (w / w) tryptophan, its hydrate or salt thereof; (k) about 4% to about 9% (w / w) valine, its hydrate or salt thereof; (l) about 7% to about 11% (w / w) arginine, its hydrate or salt thereof; (m) about 2% to about 4% (w / w) glutamine, its hydrate or salt thereof; (n) about 4% to about 7% (w / w) alanine, its hydrate or salt thereof; (o) about 8% to about 11% (w / w) aspartic acid, its hydrate or salt thereof; (p) about 4% to about 7% (w / w) asparagine, its hydrate or salt thereof; and (q) about 4% to about 8% (w / w) glutamic acid, its hydrate or salt thereof. This disclosureAny composition of the content may contain cysteine ​​instead of cystine, or contain cystine instead of cysteine.

[0088] In some embodiments, the composition may comprise at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the following: a) about 4% to about 6% (w / w) of histidine, its hydrate, or a salt thereof; b) about 5% to about 7% (w / w) of isoleucine, its hydrate, or a salt thereof; c) about 11% to about 13% (w / w) of leucine, its hydrate, or a salt thereof; d) about 8% to about 10% (w / w) of lysine, its hydrate, or a salt thereof; e) about 2% to about 4% (w / w) of methionine, its hydrate, or a salt thereof; f) about 6% to about 8% (w / w) of phenylalanine, its hydrate, or a salt thereof; g) about 1% to about 3% (w / w) of tyrosine, its hydrate, or a salt thereof; h) about 3% to about 5% (w / w) threonine, its hydrate or salt thereof; i) about 1% to about 3% (w / w) tryptophan, its hydrate or salt thereof; j) about 8% to about 10% (w / w) valine, its hydrate or salt thereof; k) about 7% to about 9% (w / w) arginine, its hydrate or salt thereof; l) about 3% to about 5% (w / w) alanine, its hydrate or salt thereof; m) about 4% to about 6% (w / w) aspartic acid, its hydrate or salt thereof; n) about 4% to about 7% (w / w) asparagine, its hydrate or salt thereof; or o) about 14% to about 17% (w / w) proline, its hydrate or salt thereof. In some embodiments, the composition may comprise, in unit dosage form: a) about 4% to about 6% (w / w) histidine, its hydrate or a salt thereof; b) about 5% to about 7% (w / w) isoleucine, its hydrate or a salt thereof; c) about 11% to about 13% (w / w) leucine, its hydrate or a salt thereof; d) about 8% to about 10% (w / w) lysine, its hydrate or a salt thereof; e) about 2% to about 4% (w / w) methionine, its hydrate or a salt thereof; f) about 6% to about 8% (w / w) phenylalanine, its hydrate or a salt thereof; g) about 1% to about 3% (w / w) tyrosine, its hydrate or a salt thereof; h) about 3% to about 5% (w / w) threonine, its hydrate or a salt thereof; i) about 1% to about 3% (j) (w / w) tryptophan, its hydrate or salt thereof; (j) about 8% to about 10% (w / w) valine, its hydrate or salt thereof; (k) about 7% to about 9% (w / w) arginine, its hydrate or salt thereof; (l) about 3% to about 5% (w / w) alanine, its hydrate or salt thereof; (m) about 4% to about 6% (w / w) aspartic acid, its hydrate or salt thereof; (n) about 4% to about 7%(w / w) asparagine, its hydrate or salt thereof; and (o) about 14% to about 17% (w / w) proline, its hydrate or salt thereof. Any composition of this disclosure may contain cysteine ​​instead of cystine, or contain cystine instead of cysteine.

[0089] Pharmaceutically acceptable salts.

[0090] Any molecular component (e.g., amino acid) of the pharmaceutical compositions described herein may be provided as a pharmaceutically acceptable salt. Pharmaceutically acceptable salts include, for example, acid addition salts and base addition salts. The acid added to the compound to form an acid addition salt may be an organic acid or an inorganic acid. The base added to the compound to form a base addition salt may be an organic base or an inorganic base. In some embodiments, the pharmaceutically acceptable salt is a metal salt.

[0091] Metal salts may be generated by adding an inorganic base to the compounds of this disclosure. Inorganic bases consist of a pairing of a metal cation with a basic counterion (such as hydroxide, carbonate, bicarbonate or phosphate). The metal can be an alkali metal, an alkaline earth metal, a transition metal, or a main group metal. In some embodiments, the metal is lithium, sodium, potassium, cesium, cerium, magnesium, manganese, iron, calcium, strontium, cobalt, titanium, aluminum, copper, cadmium, or zinc.

[0092] In some embodiments, the metal salt is a lithium salt, sodium salt, potassium salt, cesium salt, cerium salt, magnesium salt, manganese salt, iron salt, calcium salt, strontium salt, cobalt salt, titanium salt, aluminum salt, copper salt, cadmium salt, or zinc salt.

[0093] Ammonium salts can be produced by adding ammonia or an organic amine to the compounds of this disclosure. In some embodiments, the organic amine is triethylamine, diisopropylamine, ethanolamine, diethanolamine, triethanolamine, morpholine, N-methylmorpholine, piperidine, N-methylpiperidine, N-ethylpiperidine, dibenzylamine, piperazine, pyridine, pyrazole, imidazole, or pyrazine.

[0094] In some embodiments, the ammonium salt is a triethylamine salt, trimethylamine salt, diisopropylamine salt, ethanolamine salt, diethanolamine salt, triethanolamine salt, morpholine salt, N-methylmorpholine salt, piperidine salt, N-methylpiperidine salt, N-ethylpiperidine salt, dibenzylamine salt, piperazine salt, pyridine salt, pyrazole salt, pyridazine salt, pyrimidine salt, imidazole salt, or pyrazine salt.

[0095] Acid addition salts can be generated by adding an acid to the compounds of this disclosure. In some embodiments, the acid is an organic acid. In some embodiments, the acid is an inorganic acid. In some embodiments, the acid is hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, nitrous acid, sulfuric acid, sulfurous acid, phosphoric acid, isonicotinic acid, lactic acid, salicylic acid, tartaric acid, ascorbic acid, gentian acid, gluconic acid, glucuronic acid, succinic acid, formic acid, benzoic acid, glutamic acid, pantothenic acid, acetic acid, propionic acid, butyric acid, fumaric acid, succinic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, citric acid, oxalic acid, or maleic acid.

[0096] In some embodiments, the salt is hydrochloride, hydrobromide, hydroiodide, nitrate, nitrite, sulfate,Sulfites, phosphates, isonicotinic acid salts, lactates, salicylates, tartrates, ascorbic acid salts, gentianates, gluconates, glucurons, sucrose salts, formates, benzoates, glutamates, pantothenates, acetates, propionates, butyrates, fumarates, succinates, methanesulfonates, ethanesulfonates, benzenesulfonates, p-toluenesulfonates, citrates, oxalates, or maleates.

[0097] Vitamins The compositions of this disclosure may comprise one or more essential vitamins. In some embodiments, the compositions of this disclosure may comprise vitamin A, vitamin C, vitamin D, vitamin E, vitamin K, and vitamin B. In some embodiments, the compositions of this disclosure may comprise thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), biotin (vitamin B7), folate (vitamin B9), or cobalamin (vitamin B12). In some embodiments, the compositions of this disclosure may comprise fat-soluble vitamins, such as vitamin A, vitamin D, vitamin E, or vitamin K. In some embodiments, the compositions of this disclosure may comprise water-soluble vitamins, such as vitamin C and vitamin B. In some embodiments, the compositions of this disclosure may comprise water-soluble vitamins, such as vitamin B, such as thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), biotin (vitamin B7), folate (vitamin B9), or cobalamin (vitamin B12).

[0098] In some embodiments, the compositions of this disclosure may comprise vitamin A, vitamin B, vitamin C, vitamin D, and vitamin E. In some embodiments, the compositions of this disclosure may comprise vitamin A, vitamin C, vitamin D, vitamin E, thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), biotin (vitamin B7), folate (vitamin B9), or cobalamin (vitamin B12).

[0099] The compositions of this disclosure may contain vitamins at the recommended dietary allowance for adult males. In some embodiments, the compositions of this disclosure contain the following vitamins in the recommended dietary intake for adult males: vitamin A, 900 μg; vitamin C, 90 mg; vitamin D, 15 μg; vitamin E, 15 mg; vitamin K, 120 μg; thiamine, 1.2 mg; riboflavin, 1.3 mg; niacin, 16 mg; pantothenic acid, 5 mg; and pyridoxine, 1.3 mg.mg; biotin, 30 μg; folate, 400 μg; and choline, 550 mg. The compositions of this disclosure may contain the recommended dietary intake of vitamins for adult women. In some embodiments, the compositions of this disclosure contain the recommended dietary intake of vitamins for adult women: vitamin A, 700 μg; vitamin C, 75 mg; vitamin D, 15 μg; vitamin E, 15 mg; vitamin K, 90 μg; thiamine, 1.1 mg; riboflavin, 1.1 mg; niacin, 14 mg; pantothenic acid, 5 mg; pyridoxine, 1.3 mg; biotin, 30 μg; folate, 400 μg; and choline, 425 mg.

[0100] The compositions of this disclosure may contain about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% of the recommended dietary intake of vitamins in adult men or women. In some embodiments, the compositions of this disclosure may contain any one of about 20%, about 30%, about 40%, about 50%, or about 60% of the recommended dietary intake of vitamins in adult men or women. In some embodiments, the compositions of this disclosure may contain any one of about 30% of the recommended dietary intake of vitamins in adult men or women. In some embodiments, the compositions of this disclosure may contain any one of about 50% of the recommended dietary intake of vitamins in adult men or women.

[0101] Minerals The compositions of this disclosure may contain one or more minerals or elements. In some embodiments, the compositions of this disclosure may contain calcium, chromium, copper, fluoride, iodide, iron, magnesium, manganese, molybdenum, phosphorus, selenium, zinc, potassium, sodium, or chloride.

[0102] The compositions of this disclosure may contain the recommended daily amount of an element or mineral in adult males. In some embodiments, the compositions of this disclosure contain the element or mineral in the recommended daily amount in adult males: calcium, 1000 mg; chromium, 35 μg; copper, 900 μg; fluoride, 4 mg; iodide, 150 μg; iron, 8 mg; magnesium, 400 mg; manganese, 2.3 mg; molybdenum, 45 μg; phosphorus, 700 mg; selenium, 55 μg; zinc, 11 mg; potassium, 3400 mg; sodium, 1500 mg; or chloride, 2.3 g. The compositions of this disclosure may contain the element or mineral in the recommended daily amount in adult females. In some embodiments, the compositions of this disclosure contain the recommended daily intake of the following elements or minerals for adult women: calcium, 1000 mg; chromium, 25 μg; copper, 900 mg.μg; fluoride, 3 mg; iodide, 150 μg; iron, 18 mg; magnesium, 310 mg; manganese, 1.8 mg; molybdenum, 45 μg; phosphorus, 700 mg; selenium, 55 μg; zinc, 8 mg; potassium, 2600 mg; sodium, 1500 mg; or chloride, 2.3 g. Specification 13 / 87 pages 15 CN 121445725 A

[0103] The compositions of this disclosure may contain about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95% or about 100% of the recommended dietary intake of an element or mineral in an adult male or female. In some embodiments, the compositions of this disclosure may contain about 20%, about 30%, about 40%, about 50%, or about 60% of any one of the elements or minerals recommended for dietary intake in adult men or women. In some embodiments, the compositions of this disclosure may contain about 30% of any one of the elements or minerals recommended for dietary intake in adult men or women. In some embodiments, the compositions of this disclosure may contain about 50% of any one of the elements or minerals recommended for dietary intake in adult men or women.

[0104] Lipids The compositions of this disclosure may contain fats. In some embodiments, the pharmaceutical compositions of this disclosure may contain saturated fats, trans fats, polyunsaturated fats, or monounsaturated fats. In some embodiments, the compositions of this disclosure may contain saturated fats, trans fats, polyunsaturated fats, and monounsaturated fats.

[0105] In some embodiments, the compositions of this disclosure may comprise about 1 g, about 2 g, about 3 g, about 4 g, about 5 g, about 6 g, about 7 g, about 8 g, about 9 g, or about 10 g of combined fat content. In some embodiments, the compositions of this disclosure may comprise about 5 g of combined fat content.

[0106] In some embodiments, the compositions of this disclosure comprise cholesterol. In some embodiments, the compositions of this disclosure comprise about 100 mg / serving of cholesterol. In some embodiments, the compositions of this disclosure comprise about 50 mg / serving of cholesterol.

[0107] Carbohydrates In some embodiments, the compositions of this disclosure comprise carbohydrates, such as sugars, starches, or complex carbohydrates. In some embodiments, the compositions of this disclosure comprise sugars, such as corn syrup, fructose, galactose, glucose, high-fructose corn syrup, lactose, maltose, or sucrose. In some embodiments, the compositions of this disclosure include...Contains sugar alcohols. In some embodiments, the compositions of this disclosure contain starch. In some embodiments, the compositions of this disclosure contain resistant starch, such as oat starch, rice starch, legume starch, potato starch, green banana starch, or Hi-Maize® flour.

[0108] In some embodiments, the compositions of this disclosure contain complex carbohydrates, such as fiber. In some embodiments, the compositions of this disclosure contain soluble fiber. In some embodiments, the compositions of this disclosure contain soluble fiber obtained from food sources such as oatmeal, flaxseed, barley, dried peas, apples, or carrots. In some embodiments, the compositions of this disclosure contain insoluble fiber. In some embodiments, the compositions of this disclosure contain insoluble fiber obtained from food sources such as seeds, nuts, dark green leafy vegetables, or bran. In some embodiments, the compositions of this disclosure contain fiber, such as inulin, methylcellulose, plantain, or wheat dextrin.

[0109] Pharmaceutical Excipients The compositions of this disclosure may contain at least one pharmaceutical excipient, such as an anti-adhesion agent, adhesive, coating agent, colorant, disintegrant, flavoring agent, preservative, adsorbent, sweetener, or mediator. In some embodiments, the compositions of this disclosure contain a colorant and a flavoring agent. In some embodiments, the compositions of this disclosure contain a colorant, a flavoring agent, and a sweetener. In some embodiments, the compositions of this disclosure contain a flavoring agent, a sweetener, and a preservative.

[0110] A. Anti-adhesion Agent The compositions of this disclosure may contain an anti-adhesion agent. In some embodiments, the compositions of this disclosure may contain an anti-adhesion agent, such as magnesium stearate.

[0111] B. Adhesive The compositions of this disclosure may contain at least one adhesive to hold the composition together. In some embodiments, the compositions of this disclosure may contain an adhesive, such as a sugar, protein, or synthetic polymer. In some embodiments, the compositions of this disclosure may comprise disaccharides (e.g., sucrose or lactose), polysaccharides or polysaccharide derivatives (e.g., starch, cellulose, modified cellulose, cellulose ethers), or sugar alcohols (e.g., xylitol, sorbitol, or mannitol). In some embodiments, the compositions of this disclosure may comprise protein binders, such as gelatin. In some embodiments, the compositions of this disclosure may comprise synthetic polymer binders, such as polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG).

[0112] C. Preservatives The compositions of this disclosure may comprise at least one preservative. In some embodiments, the compositions of this disclosure may comprise antioxidants or antimicrobial agents. Antioxidants delay or prevent the composition from deteriorating through oxidation mechanisms.The antimicrobial agent inhibits the growth of putrefactive or pathogenic microorganisms in the composition.

[0113] In some embodiments, an antioxidant is added to the composition to delay or prevent the auto-oxidation or enzymatic oxidation of unsaturated fatty acids. In some embodiments, the compositions of this disclosure contain at least one of the following: ascorbic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), citric acid, sulfite, tert-butylhydroquinone (TBHQ), or tocopherol. In some embodiments, the compositions of this disclosure contain ascorbic acid. In some embodiments, the compositions of this disclosure contain BHT. In some embodiments, the compositions of this disclosure contain citric acid.

[0114] In some embodiments, the compositions of this disclosure contain an antioxidant of about 100 mg / kg, about 200 mg / kg, about 300 mg / kg, about 400 mg / kg, about 500 mg / kg, about 600 mg / kg, about 700 mg / kg, about 800 mg / kg, about 900 mg / kg, or about 1000 mg / kg. In some embodiments, the compositions of this disclosure contain an antioxidant of up to about 100 mg / kg, up to about 200 mg / kg, up to about 300 mg / kg, up to about 400 mg / kg, up to about 500 mg / kg, up to about 600 mg / kg, up to about 700 mg / kg, up to about 800 mg / kg, up to about 900 mg / kg, or up to about 1000 mg / kg.

[0115] In some embodiments, an antimicrobial agent is added to the composition to delay or prevent the growth of putrefactive or pathogenic microorganisms in the composition. In some embodiments, the compositions of this disclosure comprise at least one of the following: acetic acid, benzoic acid, natamycin, nisin, nitrate, nitrite, propionic acid, sorbic acid, sulfite, or sulfur dioxide.

[0116] In some embodiments, the compositions of this disclosure comprise an antimicrobial agent at about 100 mg / kg, about 200 mg / kg, about 300 mg / kg, about 400 mg / kg, about 500 mg / kg, about 600 mg / kg, about 700 mg / kg, about 800 mg / kg, about 900 mg / kg, or about 1000 mg / kg. In some embodiments, the compositions of this disclosure contain up to about 100 mg / kg, up to about 200 mg / kg, up to about 300 mg / kg, up to about 400 mg / kg, up to about 500 mg / kg, up to about 600 mg / kg, up to about 700 mg / kg, up to about 800 mg / kg, up to about 900 mg / kg, or up to about 1000 mg / kg.Antimicrobial agents.

[0117] D. Coloring agents The compositions of this disclosure may contain at least one coloring agent. In some embodiments, the compositions of this disclosure contain natural or synthetic coloring agents.

[0118] In some embodiments, the compositions of this disclosure contain natural coloring agents. In some embodiments, the compositions of this disclosure contain anthocyanins. In some embodiments, the compositions of this disclosure contain anthocyanins, such as pelargonidin-3-glucoside obtained from strawberry (Fragaria species) or malvidin-3-glucoside obtained from grape (Vitis species). In some embodiments, the compositions of this disclosure contain betacyanin. In some embodiments, the compositions of this disclosure contain betacyanin, such as betaine obtained from beetroot (Beta vulgaris). In some embodiments, the compositions of this disclosure contain carotenoids. In some embodiments, the compositions of this disclosure contain carotenoids, such as cinnamon derived from Bixa Orellana; crocin derived from Crocus sativus; capsanthin derived from Capsicum annuum; β-carotene derived from Daucus carota; or canthaxanthin derived from Cantharides cinnabarinus. In some embodiments, the compositions of this disclosure contain phenols. In some embodiments, the compositions of this disclosure contain phenols, such as curcumin derived from Cuycuma longa.

[0119] In some embodiments, the compositions of this disclosure contain synthetic colorants. In some embodiments, the compositions of this disclosure contain Allura Red AC, Brilliant Blue FCF, Erythrosine, Fast Green FCF, Indigo Carmine, Sunset Yellow FCF, or Tartrazine. In some embodiments, the compositions of this disclosure comprise FD&C Red 40, FD&C Blue 1, FD&C Red 3, FD&C Green 3, FD&C Blue 2, FD&C Yellow 6, or FD&C Yellow 5. In some embodiments, the compositions of this disclosure comprise E133, E127, E132, E110, or E102.

[0120] E. Flavoring The compositions of this disclosure may comprise at least one flavoring agent. In some embodiments, the compositions of this disclosure comprise...The compositions may contain natural flavoring substances, natural-identical flavoring substances, or artificial flavoring substances. In some embodiments, the compositions of this disclosure may contain natural flavoring substances, such as spices, fruit juices, or vegetable juices. In some embodiments, the compositions of this disclosure may contain natural-identical flavoring substances, such as vanillin.

[0121] In some embodiments, the compositions of this disclosure may contain artificial flavoring substances, such as allylpyrazine, methoxypyrazine, 2-isobutyl-3-methoxypyrazine, acetyl-L-pyrazine, 2-acetoxypyrazine, aldehydes, alcohols, esters, ketones, pyrazines, phenols, or terpenes.

[0122] F. Sweeteners The compositions of this disclosure may contain at least one sweetener. In some embodiments, the compositions of this disclosure contain sucrose, glucose, fructose, corn syrup, high-fructose corn syrup, or sugar alcohols. In some embodiments, the compositions of this disclosure contain sugar alcohols, such as sorbitol, mannitol, or xylitol. In some embodiments, the compositions of this disclosure comprise fructose.

[0123] In some embodiments, the compositions of this disclosure comprise a synthetic sweetener. In some embodiments, the compositions of this disclosure comprise saccharin, cyclosulfonate, aspartame, or acesulfame K. In some embodiments, the compositions of this disclosure comprise aspartame.

[0124] In some embodiments, the compositions of this disclosure may contain a sweetener in amounts of about 0.5 g / part, about 1 g / part, about 1.5 g / part, about 2 g / part, about 2.5 g / part, about 3 g / part, about 3.5 g / part, about 4 g / part, about 4.5 g / part, about 5 g / part, about 5.5 g / part, about 6 g / part, about 6.5 g / part, about 7 g / part, about 7.5 g / part, about 8 g / part, about 8.5 g / part, about 9 g / part, about 9.5 g / part, or about 10 g / part. In some embodiments, the compositions of this disclosure may contain about 1 g / part of sweetener. In some embodiments, the compositions of this disclosure may contain about 2.5 g / part of sweetener. In some embodiments, the compositions of this disclosure may contain about 5 g / part of sweetener.

[0125] G. Processing Agent Specification 16 / 87 pages 18 CN 121445725 A The compositions of this disclosure may contain at least one processing additive. In some embodiments, the compositions of this disclosure may contain anti-caking agents, bleaching agents, chelating agents, clarifying agents, conditioning agents, emulsifiers, wetting agents, pH control agents, stabilizers, or thickeners. In some embodiments, the compositions of this disclosure may contain anti-caking agents (such as aluminum silicate).Sodium bromate), chelating agents (such as ethylenediaminetetraacetic acid (EDTA)), conditioning agents (such as potassium bromate), or pH control agents (such as citric acid or lactic acid). In some embodiments, the compositions of this disclosure may contain wetting agents (such as glycerin) or stabilizers and thickeners (such as pectin, gelatin, carrageenan, or guar gum).

[0126] Formulation The compositions of the present invention may be, for example, an immediate-release form or a controlled-release formulation. Immediate-release formulations may be formulated to allow the compound to act rapidly. Non-limiting examples of immediate-release formulations include readily soluble formulations. Controlled-release formulations may be pharmaceutical formulations adapted such that the release rate and release profile of the active agent can be matched to physiological and time-dependent therapeutic needs, or alternatively, formulated to influence the release of the active agent at a programmed rate. Non-limiting examples of controlled-release formulations include granules, delayed-release granules, hydrogels (e.g., synthetic or naturally derived hydrogels), other gelling agents (e.g., dietary fiber that forms a gel), matrix-based formulations (e.g., formulations comprising a polymeric material in which at least one active ingredient is dispersed), particles within a matrix, polymer mixtures, and granular aggregates.

[0127] In some embodiments, the controlled-release formulation is a delayed-release form. A delayed-release form can be formulated to delay the duration of action of the compound for an extended period. A delayed-release form can be formulated to delay the release of an effective dose of one or more compounds for, for example, about 4, about 8, about 12, about 16, or about 24 hours.

[0128] Controlled-release formulations can be sustained-release forms. Sustained-release forms can be formulated to sustain, for example, the action of a compound over an extended period. Sustained-release forms can be formulated to provide an effective dose of any of the compounds described herein (e.g., providing a physiologically effective blood profile) for about 4, about 8, about 12, about 16, or about 24 hours.

[0129] Non-limiting examples of pharmaceutically acceptable excipients can be found, for example, Remington: The Science and Practice of Pharmacy, 19th edition (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., editors, Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and PharmaceuticalDosage Forms and Drug Delivery Systems, 7th Edition (Lippincott Williams & Wilkins 1999).

[0130] Dosing may be administered with the composition described herein to supplement the subject's diet. The composition described herein may be administered as a meal replacement. The composition described herein may be administered immediately before or after a meal. The composition described herein may be administered approximately 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 40 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, or 6 hours before or after a meal.

[0131] The composition described herein may be in a unit dosage form suitable for a single, precise dose. In a unit dosage form, the formulation is divided into unit doses containing an appropriate amount of the composition. In some embodiments, the unit dose may be in the form of a package containing a discrete amount of the formulation. In some embodiments, the formulation of this disclosure may be presented in a unit dosage form in a single-dose capsule. In some embodiments, the formulation of this disclosure may be presented in a single-dose, non-reclosed container. In some embodiments, the formulation of this disclosure may be presented in a resealable container, and a single dose of the formulation may be obtained by a spoon or ladle designed to dispense a single dose. In some embodiments, the formulation of this disclosure may be presented in a resealable container, and a single dose of the formulation may be obtained by a spoon or ladle designed to dispense half doses (i.e., two spoons for one dose).

[0132] The compositions described herein may be present in unit dose portions in the range of about 1 g to about 2 g, about 2 g to about 3 g, about 3 g to about 4 g, about 4 g to about 5 g, about 5 g to about 6 g, about 6 g to about 7 g, about 7 g to about 8 g, about 8 g to about 9 g, about 9 g to about 10 g, about 10 g to about 11 g, about 11 g to about 12 g, about 12 g to about 13 g, about 13 g to about 14 g, about 14 g to about 15 g, about 15 g to about 16 g, about 16 g to about 17 g, about 17 g to about 18 g, about 18 g to about 19 g, about 19 g to about 20 g, about 20 g to about 21 g, about 21 g to about 22 g, about 22 g to about 23 g, about 23 g to about 24 g, or about 24 g to about 25 g.

[0133] The compositions described herein may be in quantities of about 1 g, about 2 g, about 3 g, about 4 g, about 5 g, about 6 g, about 7 g, about 8 g, about 9 g, about 10 g, about 11 g, about 12 g, about 13 g, about 14 g, about 15 g, about 16 g, about 17 g, etc.The composition is present in units of doses of about 10 g, about 12 g, about 15 g, 20 g, or 24 g. In some embodiments, the composition described herein is present in units of doses of about 10 g, 12 g, 15 g, 20 g, or 24 g.

[0134] In some embodiments, the composition described herein is present in units of doses of about 12 g. In some embodiments, the composition described herein is present in units of doses of about 12 g in a capsule. In some embodiments, the composition described herein is present in units of doses of about 15 g. In some embodiments, the composition described herein is present in units of doses of about 15 g in a capsule. In some embodiments, the composition described herein is present in units of doses of about 24 g. In some embodiments, the composition described herein is present in units of doses of about 24 g in a capsule.

[0135] In some embodiments, the dosage of the composition of this disclosure can be expressed as the amount of drug divided by the mass of the subject, for example, the number of grams of drug per kilogram of subject body weight. In some embodiments, the therapeutically effective amount of the composition of this disclosure is about 0.1 g / kg / day to about 0.2 g / kg / day, about 0.2 g / kg / day to about 0.3 g / kg / day, about 0.3 g / kg / day to about 0.4 g / kg / day, about 0.4 g / kg / day to about 0.5 g / kg / day, about 0.5 g / kg / day to about 0.6 g / kg / day, about 0.6 g / kg / day to about 0.7 g / kg / day, about 0.7 g / kg / day to about 0.8 g / kg / day, about 0.8 g / kg / day to about 0.9 g / kg / day, about 0.9 g / kg / day to about 1.0 g / kg / day, about 1.0 g / kg / day to about 1.1 g / kg / day, about 1.1 g / kg / day to about 1.2 g / kg / day, and about 1.2 g / kg / day to about 1.3 g / kg / day. g / kg / day, about 1.3 g / kg / day to about 1.4 g / kg / day, or about 1.4 g / kg / day to about 1.5 g / kg / day. In some embodiments, the therapeutically effective amount of the composition of this disclosure is about 0.4 g / kg / day to about 0.5 g / kg / day. In some embodiments, the therapeutically effective amount of the composition of this disclosure is about 0.6 g / kg / day to about 0.7 g / kg / day. In some embodiments, the therapeutically effective amount of the composition of this disclosure is about 0.8 g / kg / day to about 0.9 g / kg / day.

[0136] The compositions described herein can be provided to a subject to achieve an amount of protein per unit of the subject's body weight. In someIn some embodiments, the composition described herein may be provided to a subject to achieve a range of about 0.2 g of protein to about 0.4 g of protein, about 0.4 g of protein to about 0.6 g of protein, about 0.6 g of protein to about 0.8 g of protein, or about 0.8 g of protein to about 1 g of protein per kilogram of subject body weight. In some embodiments, the composition described herein may be provided to a subject to achieve a range of about 0.6 g of protein to about 0.8 g of protein per kilogram of subject body weight.

[0137] The composition described herein may be provided to a subject in one or more servings per day. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 servings of the composition described herein may be provided to a subject per day. In some embodiments, 3 servings of the composition described herein may be provided to a subject per day. In some embodiments, 6 servings of the composition described herein may be provided to a subject per day. In some embodiments, 9 servings of the composition described herein may be provided to a subject per day.

[0138] Instructions for Use 18 / 87 pages 20 CN 121445725 A The compositions of this disclosure can be administered to the subject in the form of a liquid beverage. In some embodiments, the beverage for the subject is prepared by dissolving one or more sacs of the composition of this disclosure in a liquid that does not contain a large amount of nutrients. In some embodiments, the beverage for the subject is prepared by dissolving one or more sacs of the composition of this disclosure in water. In some embodiments, the beverage for the subject is prepared by dissolving one or more sacs of the composition of this disclosure in fruit juice. In some embodiments, the beverage for the subject is prepared by dissolving one or more sacs of the composition of this disclosure in an electrolyte beverage.

[0139] In some embodiments, the beverage for the subject is prepared by dissolving one or more sacs of the composition of this disclosure in water, and a flavoring agent is added to the mixture. In some embodiments, at least one drop of flavoring agent (such as Mio liquid water enhancer) is added to the mixture of the pharmaceutical composition of this disclosure in water. In some embodiments, a flavoring powder (such as Squash Stix™ water enhancer) is added to a mixture of the compositions of this disclosure in water.

[0140] In some embodiments, a target beverage is prepared by dissolving one or more capsules of the compositions of this disclosure in water, and a dietary supplement gel or pre-made dietary supplement beverage is added to the mixture. In some embodiments, a dietary supplement gel (such as Vitaflo gel™) is added to a mixture of the compositions of this disclosure in water. In some embodiments, a pre-made dietary supplement beverage (such as Vitaflo cooler™) is added to...The compositions of this disclosure are in a mixture of water.

[0141] In some embodiments, the compositions are prepared as pre-made beverages in bottles or cartons.

[0142] The compositions of this disclosure can be applied to a subject, and said application may be accompanied by a food-based diet containing at least one amino acid or substantially free of at least one amino acid. In some embodiments, the application of the compositions of this disclosure is accompanied by a food-based diet containing at least one amino acid or substantially free of one amino acid. In some embodiments, the application of the compositions of this disclosure is accompanied by a food-based diet containing at least one serine or substantially free of serine. In some embodiments, the application of the compositions of this disclosure is accompanied by a food-based diet containing at least one glycine or substantially free of glycine. In some embodiments, the application of the compositions of this disclosure is accompanied by a food-based diet containing at least one or substantially free of two amino acids or their salts. In some embodiments, the application of the compositions of this disclosure is accompanied by a food-based diet containing at least one or substantially free of both serine and glycine. In some embodiments, the composition of this disclosure is administered in conjunction with a food-based diet containing low or substantially no amounts of three amino acids or their salts. In some embodiments, the composition of this disclosure is administered in conjunction with a food-based diet containing low or substantially no amounts of four amino acids or their salts. The salts of the amino acids disclosed herein may be pharmaceutically acceptable salts.

[0143] The amino acid-free composition of this disclosure may be administered with a diet containing up to about 500 mg / day, up to about 450 mg / day, up to about 400 mg / day, up to about 350 mg / day, up to about 300 mg / day, up to about 250 mg / day, up to about 200 mg / day, up to about 150 mg / day, or up to about 100 mg / day of amino acids. In some embodiments, the amino acid-free composition of this disclosure may be administered with a diet containing up to about 450 mg / day of amino acids. In some embodiments, the amino acid-free composition of this disclosure may be administered with a diet containing up to about 400 mg / day of amino acids. In some embodiments, the amino acid-free composition of this disclosure may be administered with a diet containing up to about 350 mg / day of amino acids. In some embodiments, the amino acid-free composition of this disclosure may be administered with a diet containing up to about 250 mg / day of amino acids. In some embodiments, the proline-free composition may be administered with a diet containing up to about 450 mg / day of proline. (See description on pages 19 / 87, CN 121445725 A for some embodiments.)In some embodiments, the proline-free composition is administered with a diet containing up to about 350 mg / day of proline.

[0144] The composition of this disclosure, which does not contain the first amino acid and the second amino acid, may be administered with a diet containing up to about 500 mg / day, up to about 450 mg / day, up to about 400 mg / day, up to about 350 mg / day, up to about 300 mg / day, up to about 250 mg / day, up to about 200 mg / day, up to about 150 mg / day or up to about 100 mg / day of the first amino acid and up to about 500 mg / day, up to about 450 mg / day, up to about 400 mg / day, up to about 350 mg / day, up to about 300 mg / day, up to about 250 mg / day, up to about 200 mg / day, up to about 150 mg / day or up to about 100 mg / day of the second amino acid. In some embodiments, the composition of this disclosure, which does not contain the first and second amino acids, may be administered with a diet containing up to about 450 mg / day of the first amino acid and up to about 300 mg / day of the second amino acid. In some embodiments, the composition of this disclosure, which does not contain the first and second amino acids, may be administered with a diet containing up to about 450 mg / day of the first amino acid and up to about 250 mg / day of the second amino acid. In some embodiments, the composition of this disclosure, which does not contain the first and second amino acids, may be administered with a diet containing up to about 350 mg / day of the first amino acid and up to about 250 mg / day of the second amino acid. In some embodiments, the composition of this disclosure, which does not contain the first and second amino acids, may be administered with a diet containing up to about 400 mg / day of the first amino acid and up to about 250 mg / day of the second amino acid.

[0145] The composition of this disclosure may be administered to a subject receiving a diet. In some embodiments, the composition of this disclosure is administered to a subject, and the subject receives a low-protein diet. In some embodiments, the composition of this disclosure is administered to a subject, and the subject is on a low-carbohydrate diet. In some embodiments, the composition of this disclosure is administered to a subject, and the subject is on a high-fat and low-carbohydrate diet (e.g., a ketogenic diet). In some embodiments, the composition of this disclosure is administered to a subject, and the subject is on a vegetarian diet. In some embodiments, the composition of this disclosure is administered to a subject, and the subject is on a strictly vegetarian diet.

[0146] In some embodiments, the composition of this disclosure is administered to a subject receiving a low-protein diet,The diet is also low in at least one non-essential amino acid. In some embodiments, the composition of this disclosure is applied to a subject receiving a low-protein diet that is also low in serine and glycine. In some embodiments, the composition of this disclosure is applied to a subject receiving a low-protein diet containing less than about 2 g / day, about 1.75 g / day, about 1.5 g / day, about 1.25 g / day, about 1 g / day, about 0.75 g / day, or about 0.5 g / day of serine or glycine. In some embodiments, the composition of this disclosure is applied to a subject receiving a low-protein diet containing less than about 500 mg / day, about 450 mg / day, about 400 mg / day, about 350 mg / day, about 300 mg / day, about 250 mg / day, about 200 mg / day, about 150 mg / day, about 100 mg / day, or about 50 mg / day of serine or glycine.

[0147] In some embodiments, the compositions of this disclosure are administered to a subject in conjunction with a low-glucose, whole-food diet.

[0148] In some embodiments, the compositions of this disclosure are administered to a subject in conjunction with a low-protein diet. In some embodiments, the compositions of this disclosure are administered to a subject in conjunction with a low-protein, whole-food diet. In some embodiments, the compositions of this disclosure are administered to a subject in conjunction with a low-protein, whole-food diet containing up to about 15 g of protein per day, up to about 14 g of protein per day, up to about 13 g of protein per day, up to about 12 g of protein per day, up to about 11 g of protein per day, up to about 10 g of protein per day, up to about 9 g of protein per day, up to about 8 g of protein per day, up to about 7 g of protein per day, up to about 6 g of protein per day, or up to about 5 g of protein per day. In some embodiments, as described on page 20 / 87 of CN 121445725 A, the composition of this disclosure is administered to a subject in conjunction with a low-protein, whole-food diet containing up to about 12 g of protein per day. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a low-protein, whole-food diet containing up to about 11 g of protein per day. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a low-protein, whole-food diet containing up to about 10 g of protein per day. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a low-protein, whole-food diet containing up to about 9 g of protein per day. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a low-protein, whole-food diet containing up to about 8 g of protein per day.

[0149] In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers up to about 60%, up to about 55%, up to about 50%, up to about 45%, up to about 40%, up to about 35%, up to about 30%, up to about 25%, up to about 20%, up to about 15%, up to about 10%, or up to about 5% of the daily calorie intake from carbohydrates. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers up to about 50% of the daily calorie intake from carbohydrates. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers up to about 25% of the daily calorie intake from carbohydrates. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers up to about 15% of the daily calorie intake from carbohydrates. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers up to about 9% of the daily calorie intake from carbohydrates.

[0150] In some embodiments, the composition of this disclosure is administered to a subject together with a diet that delivers up to about 10%, up to about 9%, up to about 8%, up to about 7%, up to about 6%, up to about 5%, up to about 4.5%, up to about 4%, up to about 3.5%, up to about 3%, up to about 2.5%, up to about 2%, up to about 1.5%, or up to about 1% of the daily calorie intake from protein. In some embodiments, the composition of this disclosure is administered to a subject together with a diet that delivers up to about 3% of the daily calorie intake from protein. In some embodiments, the composition of this disclosure is administered to a subject together with a diet that delivers up to about 2.5% of the daily calorie intake from protein. In some embodiments, the composition of this disclosure is administered to a subject together with a diet that delivers up to about 2% of the daily calorie intake from protein. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers up to about 1.5% of the daily calorie intake from protein.

[0151] In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers at least about 95%, at least about 90%, at least about 85%, at least about 80%, at least about 75%, at least about 70%, at least about 65%, at least about 60%, at least about 55%, at least about 50%, at least about 45%, at least about 40%, at least about 35%, or at least about 30% of the daily calorie intake from fat. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers at least about 45% of the daily calorie intake from fat. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers at least about 45% of the daily calorie intake from fat.The composition is administered to a subject in conjunction with a diet that delivers at least about 60% of the daily calorie intake from fat. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers at least about 80% of the daily calorie intake from fat. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with a diet that delivers at least about 90% of the daily calorie intake from fat.

[0152] The composition of this disclosure may be administered to a subject who is taking at least one supplement. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with an energy supplement. In some embodiments, the composition of this disclosure is administered to a subject in conjunction with an energy supplement such as caffeine, guarana, Asian ginseng, vitamin B12, or coenzyme Q10. In some embodiments, the compositions of this disclosure are administered to the subject together with an energy supplement such as caffeine, tyrosine, pyrroloquinoline quinone (PQQ), theanine, coenzyme Q10, acetyl-L-carboxylic acid (ALCAR), alpha-lipoic acid (ALA), citicoline, creatine, citrulline, beetroot powder, ashwagandha, or rhodiola rosea. In some embodiments, the compositions of this disclosure are administered to the subject together with a coenzyme Q10 supplement.

[0153] In some embodiments, the compositions of this disclosure are administered to the subject together with a micronutrient supplement. In some embodiments, the compositions of this disclosure are administered to the subject together with a multivitamin. In some embodiments, the compositions of this disclosure are administered to the subject together with a vitamin supplement such as a vitamin C or vitamin D supplement. In some embodiments, the compositions of this disclosure are administered to the subject together with a mineral supplement, such as an iron or zinc supplement.

[0154] In some embodiments, the compositions of this disclosure are administered to the subject together with an energy supplement and a micronutrient supplement. In some embodiments, the compositions of this disclosure are administered to the subject together with coenzyme Q10 and a multivitamin. In some embodiments, the compositions of this disclosure are administered to the subject together with coenzyme Q10 and a mineral supplement.

[0155] In some embodiments, the compositions of this disclosure are administered to the subject as a nutritionally complete product. In some embodiments, the compositions are administered as a meal replacement shake or powder. In some embodiments, the compositions are administered via an enteral feeding tube.

[0156] Multiple therapeutic agents can be administered in any order or simultaneously. In some embodiments, the compositions of the present invention are combined with...The treatment may be administered in combination with another therapeutic agent, before or after it. If administered simultaneously, the multiple therapeutic agents may be provided in a single uniform form or in multiple forms (e.g., as multiple individual pills). The agents may be packaged together or individually, in a single package or in multiple packages. One or all of the therapeutic agents may be administered in multiple doses. If not administered simultaneously, the time interval between multiple doses may be up to about one month.

[0157] The therapeutic agents described herein may be administered before, during or after the onset of a disease or condition, and the time interval for administering a composition containing a therapeutic agent may vary. For example, the composition may be used as a preventative agent and may be continuously administered to a subject with a condition or predisposition to reduce the likelihood of the disease or condition occurring. The composition may be administered to the subject as soon as possible during or after the onset of symptoms.

[0158] The compositions disclosed herein may be administered as soon as possible after the detection or suspicion of the onset of a disease or condition, and for the duration necessary to continue treatment of the disease. In some embodiments, the duration necessary to treat the disease is about 12 hours, about 24 hours, about 36 hours, or about 48 hours. In some implementations, the required duration of treatment is approximately 1 day, approximately 2 days, approximately 3 days, approximately 4 days, approximately 5 days, approximately 6 days, approximately 7 days, approximately 8 days, approximately 9 days, approximately 10 days, approximately 11 days, approximately 12 days, approximately 13 days, approximately 14 days, or approximately 15 days. In some implementations, the required duration of treatment is approximately 1 week, approximately 2 weeks, approximately 3 weeks, approximately 4 weeks, approximately 5 weeks, approximately 6 weeks, approximately 7 weeks, approximately 8 weeks, approximately 9 weeks, approximately 10 weeks, approximately 11 weeks, approximately 12 weeks, approximately 13 weeks, approximately 14 weeks, approximately 15 weeks, approximately 16 weeks, approximately 17 weeks, approximately 18 weeks, approximately 19 weeks, or approximately 20 weeks. In some implementation schemes, the required duration of treatment for the disease is approximately 1 month, approximately 2 months, approximately 3 months, approximately 4 months, approximately 5 months, approximately 6 months, approximately 7 months, approximately 8 months, approximately 9 months, approximately 10 months, approximately 11 months, approximately 12 months, approximately 13 months, approximately 14 months, approximately 15 months, approximately 16 months, approximately 17 months, approximately 18 months, approximately 19 months, approximately 20 months, approximately 21 months, approximately 22 months, approximately 23 months, or approximately 24 months.

[0159] In some embodiments, the duration of compound administration can be approximately 1 day, approximately 2 days, approximately 3 days, approximately 4 days, approximately 5 days, approximately 6 days, approximately 1 week, approximately 2 weeks, approximately 3 weeks, approximately 4 weeks, approximately 1 month, approximately 5 weeks, approximately 6 weeks, approximately 7 weeks, approximately 8 weeks, approximately 2 months, approximately 9 weeks, approximately 10 weeks, approximately 11 weeks, approximately 12 weeks, approximately 3 months, approximately 13 weeks, approximately 14 weeks, approximately 15 weeks, approximately 16 weeks, approximately 4 months, approximately 17 weeks, approximately 18 weeks, approximately 19 weeks, approximately 20 weeks, approximately 5 months, approximately 21 weeks, approximately 22 weeks, approximately 23 weeks, approximately 24 weeks, approximately 6 months, approximately 7 months, or approximately 8 months.The treatment duration can vary from approximately 1 month, 9 months, 10 months, 11 months, 1 year, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 2 years, 2.5 years, 3 years, 4 years, 4.5 years, 5 years, 6 years, 7 years, 8 years, 9 years, or 10 years. The treatment duration may vary for each subject.

[0160] The compositions of this disclosure can be administered continuously. In some embodiments, the compositions of this disclosure can be administered continuously for approximately 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 2 months, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 3 months, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 4 months, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 5 months, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, and 21 months. The treatment duration can vary from approximately 22 months, 23 months, 2 years, 2.5 years, 3 years, 3.5 years, 4 years, 4.5 years, 5 years, 6 years, 7 years, 8 years, 9 years, or 10 years. The treatment duration may vary for each subject.

[0161] In some embodiments, the compositions of this disclosure may be administered at an early stage of the disease. In some embodiments, the compositions of this disclosure may be administered at a later stage of the disease. In some embodiments, the compositions of this disclosure may be administered during the pre-symptomatic stage of the disease. In some embodiments, the compositions of this disclosure may be administered during the symptomatic stage of the disease. In some embodiments, the compositions of this disclosure may be administered during the severe stage of the disease.

[0162] The compositions of this disclosure may be administered intermittently. In some embodiments, the compositions of this disclosure may be administered for the first day in conjunction with a modified diet, and a normal / habitual diet (i.e., the subject's typical diet before the administration of the composition) may be administered for the second day, and the composition / modified diet and normal / habitual diet cycles may be repeated. In some embodiments, the composition of this disclosure can be administered for one day in conjunction with a modified diet, and a normal / habitual diet can be administered for one day, and the cycles of composition / modified diet and normal / habitual diet can be repeated. In some embodiments, this disclosure...The composition of this disclosure can be administered with a modified diet for 1 day, and a normal / habitual diet for 2 days, and the cycle of composition / modified diet and normal / habitual diet can be repeated. In some embodiments, the composition of this disclosure can be administered with a modified diet for 1 day, and a normal / habitual diet for 3 days, and the cycle of composition / modified diet and normal / habitual diet can be repeated. In some embodiments, the composition of this disclosure can be administered with a modified diet for 1 day, and a normal / habitual diet for 4 days, and the cycle of composition / modified diet and normal / habitual diet can be repeated. In some embodiments, the composition of this disclosure can be administered with a modified diet for 1 day, and a normal / habitual diet for 5 days, and the cycle of composition / modified diet and normal / habitual diet can be repeated. In some embodiments, the composition of this disclosure can be administered with a modified diet for 1 day, and a normal / habitual diet for 6 days, and the cycle of composition / modified diet and normal / habitual diet can be repeated.

[0163] In some embodiments, the composition of this disclosure may be administered with a modified diet for 2 days, and a normal / habitual diet (i.e., the subject's typical diet before the administration of the composition) may be administered for 1 day, and the cycle of composition / modified diet and normal / habitual diet may be repeated. In some embodiments, the composition of this disclosure may be administered with a modified diet for 2 days, and a normal / habitual diet may be administered for 2 days, and the cycle of composition / modified diet and normal / habitual diet may be repeated. In some embodiments, the composition of this disclosure may be administered with a modified diet for 2 days, and a normal / habitual diet may be administered for 3 days, and the cycle of composition / modified diet and normal / habitual diet may be repeated. In some embodiments, the composition of this disclosure may be administered with a modified diet for 2 days, and a normal / habitual diet may be administered for 4 days, and the cycle of composition / modified diet and normal / habitual diet may be repeated. In some embodiments, the composition of this disclosure may be administered with a modified diet for 2 days, and a normal / habitual diet may be administered for 5 days, and the cycle of composition / modified diet and normal / habitual diet may be repeated. Specification page 23 / 87, CN 121445725 A

[0164] In some embodiments, the composition of this disclosure can be administered with a modified diet for 3 days, and a normal / habitual diet (i.e., the typical diet of the subject before the administration of the composition) can be administered for 1 day, and the composition / modified diet and normal / habitual diet cycle can be repeated. In some embodiments, the composition of this disclosure can be administered with a modified diet for 3 days, and a normal / habitual diet can be administered for 2 days, and the composition / modified diet and normal / habitual diet cycle can be repeated.Dietary cycle. In some embodiments, the composition of this disclosure may be administered with a modified diet for 3 days, and a normal / habitual diet may be administered for 3 days, and the composition / modified diet and normal / habitual diet cycle may be repeated. In some embodiments, the composition of this disclosure may be administered with a modified diet for 3 days, and a normal / habitual diet may be administered for 4 days, and the composition / modified diet and normal / habitual diet cycle may be repeated.

[0165] In some embodiments, the composition of this disclosure may be administered with a modified diet for 4 days, and a normal / habitual diet (i.e., the typical diet of the subject before the administration of the composition) may be administered for 1 day, and the composition / modified diet and normal / habitual diet cycle may be repeated. In some embodiments, the composition of this disclosure may be administered with a modified diet for 4 days, and a normal / habitual diet may be administered for 2 days, and the composition / modified diet and normal / habitual diet cycle may be repeated. In some embodiments, the composition of this disclosure may be administered with a modified diet for 4 days, and a normal / habitual diet may be administered for 3 days, and the composition / modified diet and normal / habitual diet cycle may be repeated.

[0166] In some embodiments, the composition of this disclosure may be administered with a modified diet for 5 days, and a normal / habitual diet (i.e., the subject's typical diet before the administration of the composition) may be administered for 1 day, and the composition / modified diet and normal / habitual diet cycle may be repeated. In some embodiments, the composition of this disclosure may be administered with a modified diet for 5 days, and a normal / habitual diet may be administered for 2 days, and the composition / modified diet and normal / habitual diet cycle may be repeated. In some embodiments, the composition of this disclosure may be administered with a modified diet for 6 days, and a normal / habitual diet may be administered for 1 day, and the composition / modified diet and normal / habitual diet cycle may be repeated.

[0167] In some embodiments, the composition of this disclosure may be administered with a modified diet for the first day, and a normal / habitual diet (i.e., the subject's typical diet before the administration of the composition) may be administered for the second day, and the composition / modified diet and normal / habitual diet cycle may be repeated 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times. In some embodiments, the composition of this disclosure may be administered with a modified diet for the first day, and a normal / habitual diet may be administered for the second day, and the composition / modified diet and normal / habitual diet cycle may be repeated 5 times.

[0168] In some embodiments, the composition of this disclosure may be administered with a modified diet for the first day, and a normal / habitual diet (i.e., the typical diet of the subject before the administration of the composition) may be administered for the second day, and the composition / modified diet and normal / habitual diet cycle may be repeated for about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 1...Approximately 2 weeks, approximately 3 weeks, approximately 4 weeks, approximately 1 month, approximately 5 weeks, approximately 6 weeks, approximately 7 weeks, approximately 8 weeks, approximately 2 months, approximately 9 weeks, approximately 10 weeks, approximately 11 weeks, approximately 12 weeks, approximately 3 months, approximately 13 weeks, approximately 14 weeks, approximately 15 weeks, approximately 16 weeks, approximately 4 months, approximately 17 weeks, approximately 18 weeks, approximately 19 weeks, approximately 20 weeks, approximately 5 months, approximately 21 weeks, approximately 22 weeks, approximately 23 weeks, approximately 24 weeks, approximately 6 months, approximately 7 months, approximately 8 months, approximately 9 months, approximately 10 months, approximately 11 months, approximately 1 year, approximately 13 months, approximately 14 months, approximately 15 months, approximately 16 months, approximately 17 months, approximately 18 months, approximately 19 months, approximately 20 months, approximately 21 months, approximately 22 months, approximately 23 months, approximately 2 years, approximately 2.5 years, approximately 3 years, approximately 3.5 years, approximately 4 Treatment duration may be approximately 1 year, 4.5 years, 5 years, 6 years, 7 years, 8 years, 9 years, or 10 years. The treatment duration may vary for each subject.

[0169] The compositions of this disclosure may be administered 1, 2, 3, 4, 5, 6, 7, or 8 times daily, throughout the entire 24-hour period. In some embodiments, the compositions of this disclosure may be administered once daily. In some embodiments, the compositions of this disclosure may be administered twice daily. In some embodiments, the compositions of this disclosure may be administered three times daily. In some embodiments, the compositions of this disclosure may be administered four times daily. In some embodiments, the compositions of this disclosure (page 24 / 87, CN 121445725 A) may be administered five times daily. In some embodiments, the compositions of this disclosure may be administered six times daily.

[0170] The compositions described herein may be in unit dosage forms suitable for single-dose administration of precise doses. In unit dosage forms, the formulation is divided into unit doses containing appropriate amounts of one or more compounds. Unit doses may be in the form of packages containing discrete amounts of the formulation. Aqueous suspension compositions may be packaged in single-dose, non-resealable containers. Multi-dose, resealable containers may be used, for example, with or without a preservative composition.

[0171] In some embodiments, the composition is administered to the subject throughout the day. In some embodiments, the composition is administered to the subject with a meal. In some embodiments, the composition is administered to the subject with a snack. In some embodiments, the composition is not administered to the subject with a meal. In some embodiments, the composition is administered to the subject at equal intervals throughout the day. In some embodiments, the first dose is administered before breakfast, the second dose with breakfast, the third dose with lunch, the fourth and fifth doses with dinner, and the sixth dose before bedtime.

[0172] The compositions provided herein may be administered in combination with other therapies, such as chemotherapy agents, radiation, surgery, anti-inflammatory agents, immunotherapy, biologics, and selected vitamins. Other agents may be administered before, after, or simultaneously with the pharmaceutical composition.

[0173] Methods of using the compositions disclosed herein.

[0174] This disclosure provides methods for treating a subject. The compositions disclosed herein can be used to treat any disease. In some embodiments, the compositions disclosed herein are used to treat cancer in a subject in need. Modifying the subject's diet and nutrients can have the desired health benefits and can effectively treat the disease.

[0175] Based on the needs of a particular disease and / or patient, this disclosure provides methods for broad treatment recommendations for a subject and methods for subject-specific treatment recommendations. The treatment method may include one of the following steps: determining the subject's nutrient levels; detecting the presence of a disease in the subject based on the determination; and recommending at least one broad or subject-specific treatment to the subject to improve disease symptoms.

[0176] In some embodiments, the compositions disclosed herein can be used to manage a disease or condition through dietary intervention. In some embodiments, the compositions disclosed herein can be used as part of a treatment plan for a particular disease or condition.

[0177] In some embodiments, the subject has cancer. Cancer is caused by uncontrolled proliferation of cells that invade adjacent and distal tissues, leading to death. Cancer cells typically possess underlying genetic or epigenetic abnormalities affecting coding and regulatory regions of the genome. Genetic abnormalities in cancer cells can alter protein structure, dynamics, and expression levels, thereby altering cancer cell metabolism. Changes in the cell cycle can cause cancer cells to proliferate at a much faster rate than normal cells. With increased metabolic rates and proliferation, cancer tissues have much higher nutrient requirements compared to normal tissues.

[0178] Cancer cells exhibit nutrient malnutrition and have much higher nutrient requirements compared to normal tissues. As an adaptation to meet increased nutrient requirements, cancer cells can upregulate glucose and amino acid transporters on the cell membrane to obtain more nutrients from the circulation. Cancer cells can also reconnect metabolic pathways by enhancing glycolysis and glutamine breakdown to maintain a sustained high rate of ATP production or energy supply. Glucose and amino acids are highly required nutrients in cancer cells. Some cancer cell types and tumor tissues are known to be malnutritive for specific amino acids. The malnutrition of different amino acids in cancer can make cancer types susceptible to amino acid starvation therapy.

[0179] When mammalian cells experience amino acid starvation, the cells undergo a homeostatic response to amino acid deficiency. Amino acid deficiency can trigger general amino acid control pathways involving the transfer of cellular resources and energy to the expression of membrane transport proteins, growth hormones, and metabolic enzymes to achieve amino acid homeostasis. Upregulation of membrane transport proteins can enhance amino acid uptake. (See page 27 of the manual, CN 121445725 A)Cells can also recycle proteins and organelles to regenerate non-essential amino acids through autophagy. Cells attempt to maintain amino acid homeostasis through general amino acid control pathways and autophagy. Tumor tissues can also overcome amino acid starvation by enhancing angiogenesis to obtain a greater supply of nutrients.

[0180] When strict amino acid starvation fails to achieve homeostasis, cancer cells may inhibit protein synthesis, inhibit growth, or undergo programmed cell death. Cell death mechanisms of amino acid starvation can be caspase-dependent apoptosis, autophagic cell death, or ferroptotic cell death. Amino acid transporters, metabolic enzymes, autophagy-associated proteins, and amino acid starvation can be used to control cancer growth.

[0181] The methods disclosed herein can monitor the nutrient intake of subjects. Nutrient intake can be measured by obtaining biological samples from subjects. Biological samples can be, for example, whole blood, serum, plasma, mucous membranes, saliva, buccal swabs, urine, feces, cells, tissues, body fluids, sweat, exhaled breath, lymph, CNS fluid, and lesion exudate. Combinations of biological samples can be used in conjunction with the methods of this disclosure.

[0182] The methods of the compositions of this disclosure can slow the proliferation of cancer cell lines or kill cancer cells. Non-limiting examples of cancers that can be treated with the compounds disclosed herein include: acute lymphoblastic leukemia, acute myeloid leukemia, adrenocortical carcinoma, AIDS-related cancer, AIDS-related lymphoma, anal cancer, appendix cancer, astrocytoma, basal cell carcinoma, bile duct cancer, bladder cancer, bone cancer, brain tumors (such as cerebellar astrocytoma, cerebral astrocytoma / malignant glioma), ependymoma, medulloblastoma, and supratentorial primitive neuroectodermal tumors.Tumors, visual pathway and hypothalamic gliomas, breast cancer, bronchial adenoma, Burkitt lymphoma, carcinoma of unknown primary origin, central nervous system lymphoma, cerebellar astrocytoma, cervical cancer, childhood cancer, chronic lymphocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative disorder, colon cancer, cutaneous T-cell lymphoma, desmoplastic small round cell tumor, endometrial cancer, ependymoma, esophageal cancer. Cancer, Ewing's sarcoma, germ cell tumor, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, glioma, hairy cell leukemia, head and neck cancer, heart cancer, hepatocellular carcinoma, Hodgkin lymphoma, hypopharyngeal cancer, intraocular melanoma, islet cell carcinoma.Carcinoma, Kaposi sarcoma, kidney cancer, laryngeal cancer, lip and oral cavity cancer, liposarcoma, liver cancer, lung cancer (such as non-small cell and small cell lung cancer, page 26 / 87, CN 121445725 A), lymphoma, leukemia, macroglobulinemia, malignant fibrous histiocytoma of bone / osteosarcoma, medulloblastoma, melanoma, mesothelioma, metastatic squamous neck cancer with occult primary, mouth cancer, multiple endocrine adenoma syndrome. Endocrine neoplasia syndrome, myelodysplastic syndrome, myeloid leukemia, nasal cavity and paranasal sinus cancer, nasopharyngeal carcinoma, neuroblastoma, non-Hodgkin lymphoma, non-small cell lung cancer, oral cancer, oropharyngeal cancer, osteosarcoma / malignant fibrous histiocytoma of bone, ovarian cancer, ovarian epithelial cancer, ovarian germ cell tumor.Tumor, pancreatic cancer, pancreatic islet cell cancer, paranasal sinus and nasal cavity cancer, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytoma, pineal astrocytoma, pineal germinoma, pituitary adenoma, pleuropulmonary blastoma, plasma cell neoplasia, primary central nervous system lymphoma, prostate cancer, rectal cancer, renal cell carcinoma, renal pelvis and ureter transitional cell carcinoma. Cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sarcoma, skin cancer, Merkel cell skin carcinoma, small intestine cancer, soft tissue sarcoma, squamous cell carcinoma, stomach cancer, T-cell lymphoma, throat cancer, thymoma, thymic carcinoma, thyroid cancer, trophoblastic tumor (pregnancy), cancers of unknown primary site, urethral cancer, uterine sarcoma.Sarcoma), vaginal cancer, vulvar cancer, Waldenström macroglobulinemia, and Wilms tumor.

[0183] In some embodiments, the methods of this disclosure can be used to treat breast cancer. In some embodiments, the methods of this disclosure can be used to treat colorectal cancer. In some embodiments, the methods of this disclosure can be used to treat pancreatic cancer.

[0184] Treatment effects.

[0185] In some embodiments, this disclosure provides a composition in powder form comprising: a) essential amino acids, wherein said essential amino acids are not part of a polypeptide; b) non-essential amino acids, wherein said non-essential amino acids are not part of a polypeptide; and c) pharmaceutically acceptable excipients. In some embodiments, the composition does not contain serine, glycine, and cysteine. In some embodiments, the composition does not contain serine, glycine, and glutamic acid, glutamine, and cysteine. In some embodiments, the composition does not contain proline. In some embodiments, the composition does not contain serine (page 27 / 87, CN 121445725 A) or glycine.

[0186] Application of the composition can regulate the serum amino acid level of at least one amino acid. In some embodiments, application of the amino acid-free composition can reduce the serum amino acid level of the amino acid. In some embodiments, application of the amino acid-free composition can reduce the serum amino acid level of the amino acid by about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, or about 80% to about 90%. In some embodiments, application of the amino acid-free composition can reduce the serum amino acid level of the amino acid by about 10% to about 20%. In some embodiments, application of the amino acid-free composition can reduce the serum amino acid level of the amino acid by about 20% to about 30%. In some embodiments, application of the amino acid-free composition can reduce serum amino acid levels by about 5%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95%. In some embodiments, application of the amino acid-free composition can reduce serum amino acid levels by about 10%. In some embodiments, application of the amino acid-free composition can reduce serum amino acid levels by about 20%. In some embodiments, application of the amino acid-free composition can reduce serum amino acid levels by about 30%.

[0187] Applying a composition that does not contain the first amino acid can reduce serum amino acid levels of at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. In some embodiments, applying a composition that does not contain the first amino acid can reduce serum amino acid levels of at least the first and second amino acids. In some embodiments, applying a composition that does not contain the first amino acid can reduce serum amino acid levels of at least the first, second, and third amino acids. In some embodiments, applying a composition that does not contain the first amino acid can reduce serum amino acid levels of at least the first, second, third, and fourth amino acids. In some embodiments, applying a composition that does not contain the first amino acid can reduce serum amino acid levels of at least the first, second, third, fourth, and fifth amino acids.

[0188] Applying a composition of this disclosure that does not contain amino acids can alter serum amino acid levels for a prolonged period of time. In some embodiments, applying a composition of this disclosure that does not contain amino acids can lower serum amino acid levels for a prolonged period of time. In some embodiments, application of the amino acid-free composition of this disclosure can reduce serum amino acid levels for at least about 4 hours, at least about 8 hours, at least about 12 hours, at least about 16 hours, at least about 20 hours, at least about 24 hours, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days, at least about 8 days, at least about 9 days, at least about 10 days, at least about 11 days, at least about 12 days, at least about 13 days, at least about 14 days, at least about 3 weeks, at least about 4 weeks, at least about 5 weeks, at least about 6 weeks, at least about 7 weeks, at least about 8 weeks, at least about 9 weeks, at least about 10 weeks, at least about 11 weeks, or at least about 12 weeks. In some embodiments, application of the amino acid-free composition of this disclosure can reduce serum amino acid levels for at least about 4 hours and at least about 2 days. In some embodiments, administration of the amino acid-free composition of this disclosure can reduce serum amino acid levels for at least about 4 hours and at least about 4 days. In some embodiments, administration of the amino acid-free composition of this disclosure can reduce serum amino acid levels for at least about 4 hours and at least about 2 weeks. In some embodiments, administration of the amino acid-free composition of this disclosure can reduce serum amino acid levels for at least about 4 hours and at least about 4 weeks.

[0189] The compositions of this disclosure can reduce cell proliferation in a subject. In some embodiments, administration of the compositions of this disclosure can reduce cell proliferation in a subject by about 5% to about 10% compared to a subject not given the dietary composition.About 10% to about 15%, about 15% to about 20%, about 20% to about 25%, about 25% to about 30%, about 35% to about 40%, about 40% to about 45%, about 45% to about 50%, about 50% to about 75%, about 75% to about 100%, about 100% to about 125%, about 125% to about 150%, about 150% to about 175%, or about 175% to about 200%. In some embodiments, the compositions of this disclosure can reduce cell proliferation in subjects receiving cancer therapy compared to subjects receiving cancer therapy but not receiving the compositions of this disclosure. In some embodiments, applying the compositions of this disclosure can reduce cell proliferation in subjects by about 20% to about 25% compared to subjects not receiving the dietary compositions. In some embodiments, applying the compositions of this disclosure can reduce cell proliferation in subjects by about 50% to about 75% compared to subjects not receiving the dietary compositions.

[0190] In some embodiments, application of the composition of this disclosure can reduce cell proliferation in a subject by about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 75%, about 100%, about 125%, about 150%, about 175%, or about 200% compared to a subject not receiving the dietary composition. In some embodiments, the composition of this disclosure can reduce cell proliferation in a subject receiving cancer therapy compared to a subject receiving cancer therapy but not receiving the composition of this disclosure. In some embodiments, application of the composition of this disclosure can reduce cell proliferation in a subject by about 20% compared to a subject not receiving the dietary composition. In some embodiments, application of the composition of this disclosure can reduce cell proliferation in a subject by about 30% compared to a subject not receiving the dietary composition. In some embodiments, application of the composition of this disclosure can reduce cell proliferation in a subject by about 50% compared to a subject not receiving the dietary composition. In some embodiments, application of the composition of this disclosure can reduce cell proliferation in a subject by about 70% compared to a subject not receiving the dietary composition.

[0191] In some embodiments, application of the composition of this disclosure can reduce the tumor volume of a subject by about 5% to about 10%, about 10% to about 15%, about 15% to about 20%, about 20% to about 25%, about 25% to about 30%, about 35% to about 40%, about 40% to about 45%, about 45% to about 50%, about 50% to about 75%, about 75% to about 100%, about 100% to about 125%, about 125% to about 150%, about 150% to about 175%, or about 175% to about 200%. In some embodiments, in patients receiving cancer therapy but not receiving this...Compared to subjects receiving cancer therapy, the compositions of this disclosure can reduce the tumor volume of subjects receiving cancer therapy. In some embodiments, application of the compositions of this disclosure can reduce the tumor volume of a subject by about 20% to about 25%. In some embodiments, application of the compositions of this disclosure can reduce the tumor volume of a subject by about 45% to about 50%.

[0192] In some embodiments, application of the compositions of this disclosure can reduce the tumor volume of a subject by about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 75%, about 100%, about 125%, about 150%, about 175%, or about 200%. In some embodiments, compared to subjects receiving cancer therapy but not receiving the compositions of this disclosure, the compositions of this disclosure can reduce the tumor volume of subjects receiving cancer therapy. In some embodiments, application of the compositions of this disclosure can reduce the tumor volume of a subject by about 20%. In some embodiments, application of the compositions of this disclosure can reduce the tumor volume of a subject by about 30%. In some embodiments, application of the composition of this disclosure can reduce the tumor volume of a subject by about 50%.

[0193] Application of the composition of this disclosure can increase the overall survival rate of a subject. In some embodiments, application of the composition of this disclosure can increase the overall survival rate of a subject by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95%. In some embodiments, the composition of this disclosure can increase the overall survival rate of a subject receiving cancer therapy compared to a subject receiving cancer therapy but not receiving the composition of this disclosure. In some embodiments, application of the composition of this disclosure can increase the overall survival rate of a subject by at least about 10%. In some embodiments, application of the composition of this disclosure can increase the overall survival rate of a subject by at least about 20%. In some embodiments, applying the composition of this disclosure can increase the overall survival rate of subjects by at least about 30%. Specification 29 / 87 pages 31 CN 121445725 A

[0194] Applying the composition of this disclosure can increase the progression-free survival rate of subjects. In some embodiments, applying the composition of this disclosure can increase the progression-free survival rate of subjects by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95%. In some embodiments, the compositions of this disclosure can increase progression-free survival in subjects receiving cancer therapy compared to subjects receiving cancer therapy but not receiving the compositions of this disclosure. In some embodiments, administration of the compositions of this disclosure can increase the overall survival of subjects by at least about 10%. In some embodiments, administration of the compositions of this disclosure can increase the overall survival of subjects by at least about 20%. In some embodiments, administration of the compositions of this disclosure can increase the overall survival of subjects by at least about 30%.

[0195] Administration of the compositions of this disclosure can increase the percentage of cancer cell death. In some embodiments, application of the composition of this disclosure can increase the percentage of cancer cell death by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95%. In some embodiments, the composition of this disclosure can increase the percentage of cancer cell death in subjects receiving cancer therapy compared to subjects receiving cancer therapy but not receiving the composition of this disclosure. In some embodiments, application of the composition of this disclosure can increase the percentage of cancer cell death by at least about 10%. In some embodiments, application of the composition of this disclosure can increase the percentage of cancer cell death by at least about 20%. In some embodiments, application of the composition of this disclosure can increase the percentage of cancer cell death by at least about 30%.

[0196] Application of the composition of this disclosure can increase the sensitivity of a subject to cancer therapy. In some embodiments, application of the composition of this disclosure can increase the sensitivity of a subject to cancer therapy by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95%. In some embodiments, application of the composition of this disclosure can increase the sensitivity of a subject to cancer therapy by at least about 10%. In some embodiments, application of the composition of this disclosure can increase the sensitivity of a subject to cancer therapy by at least about 20%. In some embodiments, application of the composition of this disclosure can increase the sensitivity of a subject to cancer therapy by at least about 30%.

[0197] Applying the compositions of this disclosure can increase the therapeutic response rate of a therapeutic agent. In some embodiments, applying the compositions of this disclosure can increase the therapeutic response rate of a therapeutic agent by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95%. In some embodiments, applying the compositions of this disclosure can increase the therapeutic response rate of a therapeutic agent by at least about 10%. In some embodiments, applying the compositions of this disclosure can increase the therapeutic response rate of a therapeutic agent by at least about 20%. In some embodiments, applying the compositions of this disclosure can increase the therapeutic response rate of a therapeutic agent by at least about 30%.

[0198] Applying the compositions of this disclosure together with a therapeutic agent can increase the efficacy of the therapeutic agent in the body of the subject compared to a subject treated with the compositions of this disclosure alone. In some embodiments, compared to a subject treated with the composition of this disclosure alone, administration of the composition of this disclosure together with a therapeutic agent increases the efficacy of the therapeutic agent in the body by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, to page 30 / 87 of the specification, 32 CN 121445725 A, at least about 80%, at least about 85%, at least about 90%, or at least about 95%. In some embodiments, administration of the composition of this disclosure together with a therapeutic agent can increase the efficacy of the therapeutic agent in the body by at least about 10% compared to a subject treated with the composition of this disclosure alone. In some embodiments, administration of the composition of this disclosure together with a therapeutic agent can increase the efficacy of the therapeutic agent in the body by at least about 20% compared to a subject treated with the composition of this disclosure alone. In some embodiments, administering the composition of this disclosure together with a therapeutic agent can increase the efficacy of the therapeutic agent in the body by at least about 30% compared to a subject treated with the composition of this disclosure alone.

[0199] Administering the composition of this disclosure to a subject together with a therapeutic agent can reduce the dosage of the therapeutic agent compared to a subject treated with a therapeutic agent alone to achieve the same result. In some embodiments, administering the composition of this disclosure to a subject together with a therapeutic agent can reduce the required dosage of the therapeutic agent by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, and at least about 35% compared to a subject treated with a therapeutic agent alone to achieve the same result.At least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95%. In some embodiments, administering the composition of this disclosure to a subject together with a therapeutic agent can reduce the required dose of the therapeutic agent by at least about 10% compared to a subject treated with a therapeutic agent alone to achieve the same result. In some embodiments, administering the composition of this disclosure to a subject together with a therapeutic agent can reduce the required dose of the therapeutic agent by at least about 20% compared to a subject treated with a therapeutic agent alone to achieve the same result. In some embodiments, administering the composition of this disclosure to a subject together with a therapeutic agent can reduce the required dose of the therapeutic agent by at least about 30% compared to a subject treated with a therapeutic agent alone to achieve the same result.

[0200] Administering the composition of this disclosure to a subject together with a therapeutic agent can reduce adverse events associated with the additional therapy compared to a subject treated with a single additional therapy. In some embodiments, administering the composition of this disclosure to a subject together with a therapeutic agent can reduce adverse events associated with the additional therapy by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, or at least about 95% compared to a subject treated with an additional therapy alone. In some embodiments, administering the composition of this disclosure to a subject together with a therapeutic agent can reduce adverse events associated with the additional therapy by at least about 10% compared to a subject treated with an additional therapy alone. In some embodiments, administering the composition of this disclosure to a subject together with a therapeutic agent can reduce adverse events associated with the additional therapy by at least about 20% compared to a subject treated with an additional therapy alone. In some embodiments, administering the composition of this disclosure to a subject together with a therapeutic agent can reduce adverse events associated with the additional therapy by at least about 30% compared to a subject treated with a separate additional therapy.

[0201] Kits The compositions of the present invention can be packaged as kits. In some embodiments, the kit includes written instructions for the administration / use of the composition. The written material may be, for example, a label. The written material may suggest the conditions and methods of administration. The instructions provide best guidance for the subject and supervising physician to achieve the best clinical outcome of the administration of the therapy. The written material may be a label. In some embodiments, the label may be approved by a regulatory agency such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), or other regulatory agencies.

[0202] Application-based guidance of the compositions of the present invention: The compositions of the present invention can be administered to a subject while receiving guidance from a guidance application. In some embodiments, the composition is in the form of a small capsule. In some embodiments, the composition is in the form of a shake. In some embodiments, the composition contains all of the subject's daily protein requirements. In some embodiments, the composition supplements other dietary requirements. Specification 31 / 87 pages 33 CN 121445725 A

[0203] In some embodiments, the guidance application can guide the subject by instructing the subject to consume a precise amount of the composition. In some embodiments, the guidance application can guide the subject regarding the food intake categories and the amount of each food. In some embodiments, the guidance application can provide meal plans to eliminate major nutrient categories (e.g., protein) so that the composition can provide the subject with the essential major nutrients.

[0204] The guidance application may include educational materials. In some embodiments, the guidance application may include educational manuals, diet records, biomarker feedback, or guidance from a nutritionist or health expert.

[0205] Examples Example 1: Amino acid preparation.

[0206] An amino acid preparation lacking seven non-essential amino acids was prepared. Table 1 shows the composition of Formulation A, which contains histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, cysteine, tyrosine, glutamine, and arginine. Table 1 also shows the amount (mg) of each amino acid contained in a 12 g capsule of the formulation.

[0207] Table 1. Formulation A Table 2 shows the amount of each amino acid administered to subjects given protein at 0.6 g / kg / day and 0.8 g / kg / day, as per the instructions for use, page 32 / 87, CN 121445725 A. The amounts of amino acids are presented in mg / kg / day.

[0208] Table 2. Formulation A; Protein at 0.6 g / kg / day and 0.8 g / kg / day Table 3 shows the amount of protein administered to patients supplemented with 0.8 g / kg / day of protein and the number of capsules containing Formulation A.

[0209] Table 3. Formulation A; Number of capsules administered to the patient (0.8 g / kg / day) Instructions for use 33 / 87 pages 35 CN 121445725 A Table 4 shows the amount of protein administered to patients supplemented with 0.6 g / kg / day of protein and the number of capsules containing Formulation A.

[0210] Table 4. Formulation A; Number of capsules administered to the patient (0.6 g / kg / day) Example 2: Amino acid formulation lacking a single amino acid.

[0211] Formulations lacking one amino acid were prepared. Tables 5-10 show formulations lacking tyrosine, arginine, glutamic acid, glutamine, aspartic acid, or alanine.

[0212] Table 5. Formulations lacking tyrosine Table 6. Formulations lacking arginine Instruction manual 34 / 87 pages 36 CN 121445725 A Table 7. Formulations lacking glutamic acid Table 8. Formulations lacking glutamine Instruction manual 35 / 87 pages 37 CN 121445725 A Table 9. Formulations lacking aspartic acid Table 10. Formulations lacking alanine Instruction manual 36 / 87 pages 38 CN 121445725 A Table 11 shows formulations supplemented with potassium and magnesium but lacking asparagine. Table 12 shows formulations supplemented with taurine and glucose but lacking proline.

[0213] Table 11. Formulations lacking asparagine. Instruction manual 37 / 87 pages 39 CN 121445725 A Table 12. Formulations supplemented with taurine and glucose but lacking proline Instruction manual 38 / 87 pages 40 CN 121445725 A Example 3: Amino acid formulations lacking more than one amino acid.

[0214] Preparations were made that lacked two amino acids. Table 13 shows preparations that lacked serine and glycine. Specification 39 / 87 pages 41 CN 121445725 A

[0215] Table 13. Preparations lacking serine and glycine Example 4: Preparations lacking three amino acids Specification 40 / 87 pages 42 CN 121445725 A Preparations were made that lacked three amino acids. Tables 14-17 show preparations that lacked asparagine, glutamine, glutamic acid, or proline.

[0216] Table 14. Preparation - Asn-Gln-Glu Table 15. Preparation - Pro-Gln-Glu Specification 41 / 87 pages 43 CN 121445725 A Table 16. Preparations lacking proline, serine, and glycine. Preparations were made that supplemented with potassium and magnesium to supplement serine, glycine, and proline. The contents of each preparation are shown in Tables 17-22. Table 17 shows potassium and magnesium supplements for formulations lacking proline, serine, and glycine. Table 18 shows potassium and magnesium supplements for formulations lacking proline, serine, and glycine. Table 19 shows potassium and magnesium supplements for formulations lacking proline, serine, and glycine. Table 20 shows potassium and magnesium supplements for formulations lacking proline, serine, and glycine. Table 21 shows formulations lacking cysteine, serine, and glycine. Table 22 shows potassium and magnesium supplements for formulations lacking serine, glycine, and cysteine.

[0217] Table 17. Formulation - Pro-Ser-Gly Instructions for Use 42 / 87 pages 44 CN 121445725 A Table 18. Formulation - Pro-Ser-Gly Instructions for Use 43 / 87 pages 45 CN 121445725 A Table 19. Formulation - Pro-Ser-Gly Instructions for Use 44 / 87 pages46 CN 121445725 A Table 20. Formulation - Pro-Ser-Gly Instructions for Use 45 / 87 pages 47 CN 121445725 A Table 21. Formulation - Cys-Ser-Gly Instructions for Use 46 / 87 pages 48 CN 121445725 A Table 22. Formulation - Cys-Ser-Gly Instructions for Use 47 / 87 pages 49 CN 121445725 A Example 5: Amino acid formulations lacking at least 4 amino acids.

[0218] Formulations lacking four amino acids were prepared. Table 23 shows formulations lacking glutamine, glutamic acid, serine, and glycine. Table 24 shows formulations lacking cysteine, proline, serine, and glycine.

[0219] Table 23. Formulation - Gln-Glu-Ser-Gly Table 24. Formulation - Cys-Pro-Ser-Gly Instructions for Use 48 / 87 pages 50 CN 121445725 A Example 6: Amino acid formulations lacking 5 amino acids.

[0220] Formulations lacking five amino acids were prepared. Tables 25-27 show formulations lacking cysteine, glutamine, glutamic acid, serine, glycine, proline, or tyrosine.

[0221] Table 25. Formulations lacking cysteine, glutamine, glutamic acid, serine, and glycine. Instructions for Use 49 / 87 pages 51 CN 121445725 A Table 26. Formulations lacking glutamine, glutamic acid, proline, serine, and glycine. Instructions for Use 50 / 87 pages 52 CN 121445725 A Table 27. Formulations lacking cysteine, proline, tyrosine, serine, and glycine. Instruction manual, pages 51 / 87, 53 CN 121445725 A, Example 7: Amino acid preparation lacking 6 amino acids.

[0222] Preparations lacking six amino acids were prepared. Tables 28 and 29 show preparations lacking cysteine, glutamine, glutamic acid, proline, serine, glycine, and tyrosine.

[0223] Table 28. Preparations lacking cysteine, glutamine, glutamic acid, proline, serine, and glycine. Instruction manual, pages 52 / 87, 54 CN 121445725 A, Table 29. Preparations lacking cysteine, tyrosine, glutamic acid, proline, serine, and glycine. Instruction manual, pages 53 / 87, 55 CN 121445725 A, Example 8: Amino acid preparation lacking 7 amino acids.

[0224] Preparations lacking seven amino acids were prepared. Tables 30 and 31 show formulations lacking alanine, aspartic acid, asparagine, glutamic acid, proline, serine, glycine, or tyrosine.

[0225] Table 30. Preparations lacking alanine, aspartic acid, asparagine, glutamic acid, proline, serine, and glycine. Instructions for Use, pages 54 / 87, 56 CN 121445725 A. Table 31. Preparations lacking cysteine, tyrosine, asparagine, glutamic acid, proline, serine, and glycine. Instructions for Use, pages 55 / 87, 57 CN 121445725 A. Example 9: Amino acid preparations lacking 8 amino acids.

[0226] Preparations lacking eight amino acids were prepared. Table 32 shows preparations lacking cysteine, tyrosine, arginine, asparagine, glutamic acid, proline, serine, and glycine.

[0227] Table 32. Preparations lacking cysteine, tyrosine, arginine, asparagine, glutamic acid, proline, serine, and glycine. Instructions for Use, pages 56 / 87, 58 CN 121445725 A. Example 10: Amino acid preparations lacking 9 amino acids.

[0228] Preparations were made that lacked nine amino acids. Tables 33 and 34 show preparations that lacked cysteine, tyrosine, glutamine, arginine, asparagine, glutamic acid, proline, serine, glycine, and tyrosine.

[0229] Table 33. Preparations that lacked cysteine, tyrosine, glutamine, arginine, asparagine, glutamic acid, proline, serine, and glycine. Specification 57 / 87 pages 59 CN 121445725 A Table 34. Preparations that lacked cysteine, tyrosine, alanine, arginine, asparagine, aspartic acid, proline, serine, and glycine. Specification 58 / 87 pages 60 CN 121445725 A Example 11: Amino acid preparations lacking 10 amino acids.

[0230] Preparations were made that lacked ten amino acids. Tables 35-38 show preparations lacking cysteine, tyrosine, glutamine, arginine, alanine, aspartic acid, arginine, glutamic acid, proline, serine, or glycine. Preparations lacking 10 amino acids contain one non-essential amino acid.

[0231] Table 35. Preparations lacking cysteine, tyrosine, glutamine, arginine, alanine, asparagine, glutamic acid, proline, serine, and glycine. Specification page 59 / 87, page 61, CN 121445725 A. Table 36. Preparations lacking cysteine, tyrosine, arginine, alanine, aspartic acid, asparagine, glutamic acid, proline, serine, and glycine. Specification page 60 / 87, page 62, CN 121445725 A. Table 37. Preparations lacking cysteine, tyrosine, glutamine, arginine, alanine, aspartic acid, asparagine, proline, serine, and glycine. Instruction manual, pages 61 / 87, 63 CN 121445725 ATable 38. Formulations lacking cysteine, tyrosine, glutamine, arginine, aspartic acid, asparagine, glutamic acid, proline, serine, and glycine. Instructions for Use, 62 / 87 pages, 64 CN 121445725 A Example 12: Amino acid formulation lacking 11 amino acids.

[0232] A formulation lacking eleven amino acids was prepared. Table 39 shows formulations lacking cysteine, tyrosine, glutamine, arginine, alanine, aspartic acid, asparagine, glutamic acid, proline, serine, and glycine. The formulation lacking 11 amino acids does not contain any non-essential amino acids.

[0233] Table 39. Formulations lacking all non-essential amino acids. Instructions for Use, 63 / 87 pages, 65 CN 121445725 A Example 13: Nutritionally complete formulation.

[0234] A nutritionally complete formulation was prepared in a box containing 237 mL of the formulation. Table 40 shows the ingredients in the nutritionally complete formulation.

[0235] Table 40. Nutritionally complete formulation instructions 64 / 87 pages 66 CN 121445725 A Instructions 65 / 87 pages 67 CN 121445725 A Example 14: Administration of the composition disclosed herein.

[0236] A target daily protein intake of 0.8 g / kg / day or 48 g / day was assigned to a 60 kg subject with cancer. The subject was prescribed to take four capsules (12 g each) containing formulation A daily. The subject mixed the capsules into a glass of water and, optionally, added droplets of flavoring agent, such as concentrated fruit-flavored beverage, 66 / 87 pages 68 CN 121445725 A. The subject drank the mixture of the composition. Figure 1 shows the addition of the composition contained in the capsule (101) to a glass of water (102); and the subject (104) drinking the mixture of the composition prepared in water (103).

[0237] The subject's consumption of other foods and beverages throughout the day was monitored. The subjects were given a detailed diet to strictly control their daily protein intake. The diet consisted of prepared meals and snacks that were low in protein and low in amino acids not present in the composition. The amino acid levels of the subjects were measured in biological samples obtained from the subjects using analytical methods, including liquid chromatography or liquid chromatography-mass spectrometry.

[0238] Example 15: Treatment of a disease.

[0239] Subjects suffering from a disease (e.g., cancer) received treatment from a medical professional. The medical professional prescribed formulation B. Formulation B was prescribed as several small capsules. The subjects mixed the capsules into a glass of water and optionally added droplets of flavoring agent, such as MiO flavoring agent droplets. The subjects drank the mixture of the composition. Figure 1 shows the composition contained in the capsules (101).The composition was added to a glass of water (102); and the subject (104) drank the mixture of the composition prepared in the water (103). Samples were taken from the subject to monitor the subject's nutrient and amino acid levels. Based on the samples, different formulations disclosed herein or adjustments were made to the amount of formulation B.

[0240] Example 16: Study evaluating the composition disclosed herein for the treatment of a subject's disease.

[0241] Studies were conducted to evaluate the effect of the composition disclosed herein on the subject's disease. Twenty subjects with cancer were enrolled in a double-blind, placebo-controlled, and randomized study. The experimental group consisted of ten subjects who were given the formulation in Table 6 in the form of small capsules. The parameters observed were the subjects' nutrient and amino acid levels before and after administration of the formulation. The control group consisted of ten subjects who were given small capsules of a powdered placebo. The placebo was administered at the same time as the formulation in the experimental group. The parameters observed were the subjects' nutrient and amino acid levels before and after administration of the placebo. After treatment, the subjects in the experimental group showed reduced tumor cell proliferation or tumor cell volume compared to the control group.

[0242] Example 17: Study of amino acid levels in healthy subjects given an amino acid preparation lacking proline.

[0243] Three healthy human subjects aged 18–60 years with a body mass index (BMI) between 18 and 30, and accustomed to a Western diet, were allowed to consume their accustomed diet (i.e., the typical diet of the subjects before the administration of the composition) for one day to establish baseline serum amino acid levels. A Western diet could be one in which approximately 50% of daily calorie intake came from carbohydrates, approximately 15% from protein, and approximately 35% from fat.

[0244] Subjects meeting the following criteria are ineligible to participate in this study: (i) those with any clinically relevant medical history or pre-existing conditions (i.e., respiratory, renal, hepatic, gastrointestinal, blood, lymphatic, neurological, cardiovascular, psychiatric, etc.); (ii) those with a history of illness or disease, or those using medications that specifically alter proline; (iii) those who have fainted or felt nauseous upon seeing a needle, blood, or blood donation; (iv) those who are ill or have recently been ill, such as those who have recently experienced fever and / or gastrointestinal discomfort (including vomiting and / or diarrhea); (v) those who are unwilling or unlikely to adhere to a low-protein diet lacking meat and dairy (milk, cheese) during the study; (vi) those accustomed to a restricted food group (e.g., carbohydrates, as with a ketogenic diet) or a diet containing specific components (e.g., gluten); (vii) those known to have food allergies to dairy, wheat, nuts, or sucralose; (vii) those who have used tobacco or nicotine in any form at the time of recruitment; and (ix) those who consume more than 500 kcal / day. mg of caffeine (e.g., consuming >4 medium-sized cups of coffee, >5 cups of tea, or >8 cups of soft drinks per day)Subjects who were unwilling to interrupt their consumption of milk coffee during the study (coffee without milk (with / without sugar or sucralose) was permitted, or coffee with coconut milk (without other forms of creamer) was permitted); (xi) subjects who were unwilling to interrupt their alcohol consumption during the study; (xii) subjects who typically exercised >2 hours per day or engaged in high-intensity, vigorous or other extreme exercise (see page 67 / 87 of CN 121445725 A); (xiii) subjects who were unwilling to adjust their exercise habits to 1) less than 60 minutes per day on each day of the study and 2) exercise only after blood was drawn after lunch; (xiv) subjects who could not speak English fluently (due to a lack of available translators during the COVID-19 pandemic); and (xv) subjects who had participated in clinical trials / experimental studies in the past 14 days.

[0245] Each subject was then fed a low-protein whole-food diet of 1613 kcal / day for five days. The diet consisted of 9 g protein / day and approximately 350 mg proline / day. 50%, 2%, and 48% of daily calories were derived from carbohydrates, protein, and fat, respectively. Throughout the five-day period, the diet was administered along with a supplemental amino acid preparation in the form of small capsules. Each capsule contained the components listed in Table 41. The number of capsules administered to each subject was adjusted so that each subject consumed a total of 0.8 g of supplement per kilogram of body weight per day. The capsules and meals were consumed at typical times of day (breakfast between 07:00 and 08:00, lunch between 12:00 and 13:00, and dinner between 18:00 and 19:00). Water (with or without a calorie-free sweetener) was available for free. Blood samples were collected from each subject 2 hours after lunch each day, and their amino acid content was analyzed by LC-MS.

[0246] The mean serum amino acid levels of the subjects, as measured during the consumption of the habitual diet (i.e., the typical diet of the subject before administration of the composition) and after the consumption of the experimental diet, are shown in Figure 2 (HD = habitual diet; ED = experimental diet). Figure 5A shows the percentage of serum proline levels at baseline of the habitual diet over the entire 5-day period (* = p < 0.05 ANOVA).

[0247] Table 41. Proline-deficient formulation. Specification 68 / 87 pages 70 CN 121445725 A Example 18: Study of amino acid levels in healthy subjects administered a proline-deficient amino acid formulation.

[0248] Four healthy human subjects recruited according to the criteria outlined in Example 17 were fed their habitual diet (i.e., the typical diet of the subject before administration of the composition) for two days to establish baseline serum amino acid levels. Each subject was then fed a low-protein whole food diet of 1613 kcal / day for five days. The diet consisted of 9 g protein / day and approximately 350Composition: mg proline / day. 50%, 2%, and 48% of daily calories are derived from carbohydrates, protein, and fat, respectively. Throughout the five-day period, meals are administered along with individual amino acid supplements in capsule form. Each capsule contains the components listed in Table 42. The number of capsules administered to each subject is adjusted so that each subject consumes a total of 0.8 g supplement per kilogram of body weight per day. Capsules and meals are consumed at typical times of day (breakfast between 07:00 and 08:00, lunch between 12:00 and 13:00 on pages 69 / 87 of the instruction manual, CN 121445725 A, and dinner between 18:00 and 19:00). Water (with or without calorie-free sweetener) is available as desired. Blood samples are collected from each subject 2 hours after lunch each day, and their amino acid content is analyzed by LC-MS.

[0249] The mean serum amino acid levels of the subjects, as measured during and after the administration of the composition, are shown in Figure 3 (HD = habitual diet; ED = experimental diet). Figure 5B shows the percentage of serum proline levels at baseline of the habitual diet over the entire 5-day period (* = p < 0.05 ANOVA).

[0250] Table 42. Proline-deficient formulations. Example 19: Study of amino acid levels in healthy subjects administered a proline-deficient taurine-supplemented amino acid formulation, page 70 / 87, CN 121445725 A.

[0251] Four healthy human subjects recruited according to the criteria outlined in Example 17 were fed their habitual diet (i.e., the typical diet of the subjects before the administration of the composition) for two days to establish baseline serum amino acid levels. Each subject was then fed a low-protein whole-food diet of 1613 kcal / day for 21 days. The diet consisted of 9 g protein / day and approximately 350 mg proline / day. 50%, 2%, and 48% of daily calories were derived from carbohydrates, protein, and fat, respectively. Throughout the 21-day period, the diet was administered along with a supplemental amino acid formulation in the form of small capsules. Each capsule contained the components listed in Table 43. The number of capsules administered to each subject was adjusted so that each subject consumed a total of 0.8 g of supplement per kilogram of body weight per day. The capsules and meals were consumed at typical times of day (breakfast between 07:00 and 08:00, lunch between 12:00 and 13:00, and dinner between 18:00 and 19:00). Water (with or without a calorie-free sweetener) was available freely. Blood samples were collected from each subject 2 hours after lunch each day, and their amino acid content was analyzed by LC-MS.

[0252] This was observed during the consumption of the habitual diet (i.e., the typical diet of the subject before the administration of the composition) and the experimental diet.The mean serum amino acid levels of the subjects measured afterward are shown in Figure 4 (HD = habitual diet; ED = experimental diet). Figure 5, C shows the percentage of serum proline levels at baseline of the habitual diet over the entire 21-day period (* = p < 0.05 ANOVA).

[0253] Table 43. Preparations of taurine supplementation for proline deficiency. Specification 71 / 87 pages 73 CN 121445725 A Example 20: Study of amino acid levels in pancreatic cancer patients administered amino acid preparations of taurine supplementation for proline deficiency.

[0254] Baseline serum proline levels were determined in four human subjects diagnosed with pancreatic cancer. Each subject was then fed a low-protein whole-food diet of 1613 kcal / day for four weeks. The diet consisted of 9 g protein / day and approximately 350 mg proline / day. 50%, 2%, and 48% of the daily calories were derived from carbohydrates, protein, and fat, respectively. Throughout the four-week period, the diet was administered along with a variety of amino acid supplements in the form of capsules. Each capsule contained the components listed in Table 44. The number of capsules administered to each subject was adjusted so that each subject consumed a total of 0.8 grams of supplement per kilogram of body weight per day. The capsules and meals were consumed at typical times of day (breakfast between 07:00 and 08:00, lunch between 12:00 and 13:00, and dinner between 18:00 and 19:00). Water (with or without calorie-free sweeteners) was consumed freely. Blood samples were collected from each subject 2 hours after lunch each day, and their serum proline levels were analyzed by LC-MS.

[0255] The mean serum proline levels of the subjects throughout the 4-week period, as a percentage of baseline (BL) levels measured during the habitual diet, are shown in Figure 6 (* = p < 0.05 ANOVA).

[0256] Table 44. Preparations of taurine supplementation for proline deficiency. Example 21: Study of amino acid levels in healthy subjects administered an amino acid preparation deficient in serine and glycine.

[0257] Healthy human subjects recruited according to the criteria outlined in Example 17 were fed their usual diet (i.e., the typical diet of the subject before the use of the composition, page 73 / 87 of the instruction manual, CN 121445725 A) for one day to establish baseline serum amino acid levels. The subjects were then fed a low-protein and low-carbohydrate diet of 1711 kcal / day for five days. The diet consisted of 10 g protein / day, approximately 420 mg proline / day, approximately 410 mg serine / day, and approximately 230 mg glycine / day. 9%, 2%, and89% were derived from carbohydrates, protein, and fat, respectively. The diet was administered along with individual doses of amino acid supplements in small capsules throughout the five-day period. Each capsule contained the components listed in Table 45. Subjects consumed a total of 0.8 g of supplement per kilogram of subject body weight throughout the day in multiple capsules. Blood samples were collected from each subject 2 hours after lunch each day, and serum amino acid levels were analyzed by LC-MS.

[0258] The mean serum amino acid levels of subjects measured during and after the consumption of the habitual diet are shown in Figure 7 (HD = habitual diet; ED = experimental diet).

[0259] Table 45. Instructions for use of a preparation lacking serine and glycine 74 / 87 pages 76 CN 121445725 A Example 22: Study of amino acid levels in healthy subjects administered an amino acid preparation lacking serine, glycine, and proline supplemented with taurine.

[0260] Three healthy human subjects recruited according to the criteria outlined in Example 17 were fed their usual diet (i.e., the subjects' typical diet before the administration of the composition) for two days to establish baseline serum amino acid levels. The subjects were then fed a low-protein, low-carbohydrate diet of 1711 kcal / day for 16–18 days. The diet consisted of 10 g protein / day, approximately 420 mg proline / day, approximately 410 mg serine / day, and approximately 230 mg glycine / day. 9%, 2%, and 89% of the daily calories were derived from carbohydrates, protein, and fat, respectively. Throughout the 16–18 day period, the diet was administered along with a supplemental amino acid preparation in the form of small capsules. Each capsule contained the components listed in Table 46. The number of capsules administered to each subject was adjusted so that each subject consumed a total of 0.8 g of supplement per kilogram of body weight per day. The small capsules and meals were consumed at typical times of day (breakfast between 07:00 and 08:00, lunch between 12:00 and 13:00, and dinner between 18:00 and 19:00). Water (with or without calorie-free sweeteners) was consumed freely. Blood samples were collected from each subject 2 hours after lunch each day, and their serum amino acid content was analyzed by LC-MS.

[0261] The mean serum amino acid levels of the subjects, as measured during and after consuming the experimental diet (i.e., the typical diet of the subject before administration of the composition), are shown in Figure 8 (HD = habitual diet; ED = experimental diet). Figure 9 shows the percentage of serum proline levels at baseline during the experimental diet (* = p < 0.05 ANOVA, BL = baseline (habitual diet); Avg = mean).

[0262] Table 46. Instructions for use of taurine supplementation for proline, serine, and glycine deficiency 75 / 87 pages 77 CN 121445725 AExample 23: Study of amino acid levels in healthy subjects given an amino acid preparation supplemented with taurine lacking serine, glycine, and proline.

[0263] Two groups, each consisting of one healthy subject (recruited according to the criteria outlined in Example 17), were fed their usual diet (i.e., the typical diet of the subject before administration of the composition) for two days to establish baseline serum amino acid levels. The first group was then fed a low-protein and low-carbohydrate diet of 1711 kcal / day for 16 days. The second group followed the same dietary protocol, except that the second group was instructed to eat their usual diet instead of the experimental diet on days 7 and 14 of the 16-day period. In each group, the experimental diet consisted of 10 g protein / day, approximately 420 mg proline / day, approximately 410 mg serine / day, and approximately 230 mg glycine / day. 9%, 2%, and 89% of the daily calories were derived from carbohydrates, protein, and fat, respectively. Instructions for Use, pages 76 / 87, CN 121445725 A

[0264] : For the entire 16-day period, the experimental diet was administered along with various doses of supplemental amino acid preparations in the form of capsules, except on days when subjects were instructed to eat their usual diet. Each capsule contained the components listed in Table 46 of Example 22. The number of capsules administered to each subject was adjusted so that each subject consumed a total of 0.8 g of supplement per kilogram of body weight per day. The capsules and meals were consumed at typical times of day (breakfast between 07:00 and 08:00, lunch between 12:00 and 13:00, and dinner between 18:00 and 19:00). Fresh water (with or without calorie-free sweetener) was available for free. Blood samples were collected from each subject 2 hours after lunch each day, and their serum amino acid content was analyzed by LC-MS.

[0265] The mean serum amino acid levels of the subjects, measured during and after consuming the habitual diet (i.e., the typical diet of the subjects before the administration of the composition), are shown in Figure 10, where Figure 10A represents the first group consuming the constant daily diet and Figure 10B represents the second group consuming the intermittent diet (HD = habitual diet; ED = experimental diet). Figure 10C shows the percentage of serum serine, glycine, and proline levels at the baseline level of the habitual diet throughout the 21-day period in both the constant and intermittent groups.

[0266] Example 24: Study of amino acid levels in healthy subjects administered an amino acid preparation supplemented with taurine that lacks serine, glycine, glutamic acid, glutamine, and cysteine.

[0267] Two groups of healthy human subjects, each consisting of two subjects (recruited according to the criteria outlined in Example 17), were fed their habitual diet (i.e., the typical diet of the subjects before the administration of the composition) for two days to establish baseline serum amino acid levels.

[0268] Then, in Group 1, subjects were fed a low-protein whole-food diet of 1613 kcal / day for four days. The diet consisted of 9 g protein / day and approximately 350 mg proline / day. 50%, 2%, and 48% of the daily calories were derived from carbohydrates, protein, and fat, respectively.

[0269] Then, in Group 2, subjects were fed a low-protein and low-carbohydrate diet of 1711 kcal / day for four days. The Group 2 diet consisted of 10 g protein / day, approximately 420 mg proline / day, approximately 410 mg serine / day, and approximately 230 mg glycine / day. 9%, 2%, and 89% of the daily calories were derived from carbohydrates, protein, and fat, respectively.

[0270] Throughout the four-day period, in each group, the diet was administered along with a supplemental amino acid preparation in the form of small capsules. Each capsule contained the components listed in Table 47. The number of capsules administered to each subject was adjusted so that each subject consumed a total of 0.8 g of supplement per kilogram of body weight per day. Small capsules and meals were consumed at typical times of day (breakfast between 07:00 and 08:00, lunch between 12:00 and 13:00, and dinner between 18:00 and 19:00). Water (with or without calorie-free sweeteners) was available for free. Blood samples were collected from each subject 2 hours after lunch each day, and serum amino acid levels were analyzed by LC-MS.

[0271] Mean serum amino acid levels as measured during and after the experimental diet are shown in Figure 11 for the 1613 kcal / day low-protein whole food group and Figure 12 for the 1711 kcal / day low-protein and low-carbohydrate group (HD = conventional diet; ED = experimental diet). Figure 13 provides a graph showing the serum serine and glycine levels of subjects before and after administration of a 1613 kcal / day low-protein diet (A) or a 1711 kcal / day low-protein, low-carbohydrate diet (B) (HD = habitual diet; ED = experimental diet; *P = 0.00019, T-test (two-sided, paired)). Figure 13C shows the mean % serum level after administration of the low-protein diet (left) and the mean % serum level after administration of the low-protein, low-carbohydrate diet (right).

[0272] Table 47. Instructions for use of formulations lacking serine, glycine, glutamic acid, glutamine and cysteine ​​77 / 87 pages 79 CN 121445725 A Embodiments The following non-limiting embodiments provide illustrative examples of the invention, but do not limit the scope of the invention.

[0273] Embodiment 1. A composition comprising, in unit dosage form: a) a non-essential amino acid or a salt thereof, wherein said non-essential amino acid or said salt thereof is not part of a polypeptide; b) a first essential amino acid or a first salt thereof and a second essential amino acid.The first essential amino acid or its second salt, wherein the first essential amino acid or its first salt and the second essential amino acid or its second salt are present in the composition in equal amounts, wherein the first essential amino acid and its first salt and the second essential amino acid and its second salt are not part of a polypeptide; and c) pharmaceutically acceptable excipients.

[0274] Embodiment 2. The composition according to Embodiment 1, wherein the first essential amino acid or its first salt is histidine, and the second essential amino acid or its second salt is isoleucine. Specification 78 / 87 pages 80 CN 121445725 A

[0275] Embodiment 3. The composition according to Embodiment 1 or 2, wherein the equal amounts are from about 2% to about 6% (w / w).

[0276] Embodiment 4. The composition according to Embodiment 1, wherein the equal amounts are from about 5.5% to about 8.3% (w / w).

[0277] Embodiment 5. The composition according to Embodiment 1, wherein the salt of the non-essential amino acid is a pharmaceutically acceptable salt, wherein the first salt is a pharmaceutically acceptable salt, and wherein the second salt is a pharmaceutically acceptable salt.

[0278] Embodiment 6. A composition comprising, in powder form: a) an essential amino acid, wherein the essential amino acid is not part of a polypeptide; b) a non-essential amino acid, wherein the non-essential amino acid is not part of a polypeptide; and c) a pharmaceutically acceptable excipient, wherein the composition does not contain serine or glycine, wherein, in a study of changes in tumor volume of a subject, the tumor volume of a subject treated with the composition is reduced by at least about 20% compared to a subject not treated with the composition.

[0279] Embodiment 7. A composition comprising, in unit dosage form: a) a non-essential amino acid or a salt thereof, wherein the non-essential amino acid or its salt is not part of a polypeptide; b) a first essential amino acid or a first salt thereof and a second essential amino acid or a second salt thereof, wherein the first essential amino acid or its first salt and the second essential amino acid or its second salt are present in equal amounts in the composition, wherein the first essential amino acid and its first salt and the second essential amino acid and its second salt are not part of a polypeptide; and c) a pharmaceutically acceptable excipient, wherein, if in a study of changes in tumor volume of a subject, the tumor volume of a subject administering the composition is reduced by at least about 20% compared to a subject administering a placebo.

[0280] Embodiment 8. A composition comprising, in powder form: a) an essential amino acid, wherein the essential amino acid is not part of a polypeptide; b) a non-essential amino acid, wherein the non-essential amino acid is not part of a polypeptide; and c) a pharmaceutically acceptable excipient.The composition contains an acceptable excipient, wherein the composition does not contain serine or glycine, and wherein, in a study of changes in tumor volume in a subject, the tumor volume of a subject receiving the composition is reduced by at least about 20% compared to a subject receiving a placebo.

[0281] Embodiment 9. The composition according to any one of Embodiments 1-8, wherein the composition does not contain at least one non-essential amino acid.

[0282] Embodiment 10. The composition according to any one of Embodiments 1-9, wherein the composition does not contain at least serine.

[0283] Embodiment 11. The composition according to any one of Embodiments 1-10, wherein the composition does not contain at least glycine.

[0284] Embodiment 12. The composition according to any one of Embodiments 1-11, wherein the composition does not contain at least proline.

[0285] Embodiment 13. The composition according to any one of Embodiments 1-12, wherein the composition does not contain at least cysteine.

[0286] Embodiment 14. The composition according to any one of Embodiments 1-13, wherein the composition does not contain at least tyrosine.

[0287] Embodiment 15. The composition according to any one of Embodiments 1-14, wherein the composition does not contain at least arginine.

[0288] Embodiment 16. The composition according to any one of Embodiments 1-15, wherein the composition is the composition described in the drug instructions page 79 / 87, 81 CN 121445725 A.

[0289] Embodiment 17. The composition according to any one of Embodiments 1-16, wherein the weight of the unit dosage form is about 12 grams.

[0290] Embodiment 18. The composition according to any one of Embodiments 1-17, wherein the composition is in powder form.

[0291] Embodiment 19. The composition according to any one of Embodiments 1-18, further comprising a preservative.

[0292] Embodiment 20. The composition according to any one of Embodiments 1-19, further comprising a pharmaceutically acceptable excipient.

[0293] Embodiment 21. The composition according to any one of Embodiments 1-20, further comprising a flavoring agent.

[0294] Embodiment 22. The composition according to any one of Embodiments 1-21, wherein the composition further comprises about 0.05% to about 2% (w / w) of taurine, its hydrate or a salt thereof.

[0295] Embodiment 23. The composition according to any one of Embodiments 1-22, wherein the composition further comprises about 1% to about 4% (w / w) of a Mg2+ source.

[0296] Embodiment 24. The composition according to Embodiment 23, wherein the Mg2+ source comprises magnesium citrate, corydalis rhizome, etc.Magnesium citrate, magnesium acetate, magnesium aspartate, magnesium threonate, magnesium glycine, magnesium chloride, magnesium sulfate, magnesium oxide, or magnesium malate, magnesium orotate, or their hydrates.

[0297] Embodiment 25. The composition according to Embodiment 23, wherein the Mg2+ source is magnesium citrate.

[0298] Embodiment 26. The composition according to Embodiment 23, wherein the Mg2+ source is magnesium aspartate, and the aspartic acid, its hydrate, or its salt is aspartic acid free acid.

[0299] Embodiment 27. The composition according to any one of Embodiments 1-26, wherein the composition further comprises about 2% to about 5% of a K+ source.

[0300] Embodiment 28. The composition according to Embodiment 27, wherein the K+ source includes potassium citrate, potassium phosphate, potassium chloride, potassium sulfate, potassium gluconate, potassium bicarbonate, potassium aspartate, potassium acetate, and potassium orotate.

[0301] Embodiment 29. The composition according to Embodiment 27, wherein the K+ source is potassium chloride.

[0302] Embodiment 30. The composition according to Embodiment 27, wherein the K+ source is potassium aspartate, and the aspartic acid, its hydrate, or its hydrate is a free aspartic acid base.

[0303] Embodiment 31. The composition according to any one of Embodiments 1-30, wherein, in a study of changes in tumor volume of a subject, the tumor volume of a subject treated with the composition is reduced by at least about 20% compared to a subject not treated with the composition.

[0304] Embodiment 32. The composition according to Embodiment 31, wherein the tumor volume is measured by caliper measurement.

[0305] Embodiment 33. A method for reducing the tumor volume of a subject, the method comprising administering to the subject a therapeutically effective amount of the composition, wherein the composition does not contain at least one non-essential amino acid, for at least one month.

[0306] Embodiment 34. The method according to Embodiment 33, wherein the subject receives a modified diet, wherein the modified diet provides at least about 50% of the daily calories from fat.

[0307] Embodiment 35. A method of treating cancer in a subject of need, wherein the subject receives a modified diet, wherein the modified diet provides up to about 50% of daily calories from carbohydrates, the method comprising administering to the subject a therapeutically effective amount of a dietary product, wherein the dietary product does not contain at least one non-essential amino acid.

[0308] Embodiment 36. The method of embodiment 35, wherein the cancer is pancreatic cancer. Specification 80 / 87 pages 82 CN 121445725 A

[0309] Embodiment 37. The method of embodiment 35, wherein the cancer is colorectal cancer.

[0310] Implementation Scheme 38. The method of Implementation Scheme 35, wherein the cancer is breast cancer.

[0311] Implementation Scheme 39. A method for reducing the mean serum amino acid level of at least one non-essential amino acid in a subject in need, the method comprising: a) administering to the subject a therapeutically effective amount of a dietary product excluding the at least one non-essential amino acid for a first time period; wherein the subject receives a modified diet during the first time period, the modified diet providing at least about 1% to at most about 40% of daily calories from carbohydrates; and b) not administering the dietary product to the subject for a second time period, wherein the subject receives a normal diet during the second time period, the normal diet providing at least about 45% of daily calories from carbohydrates.

[0312] Implementation Scheme 40. The method of Implementation Scheme 39, wherein the first time period is about 5 days.

[0313] Implementation Scheme 41. The method of Implementation Scheme 39, wherein the second time period is about 1 day.

[0314] Implementation Scheme 42. The method of Implementation Scheme 39, wherein the second time period is about 2 days.

[0315] Implementation Scheme 43. The method of Implementation Scheme 39, further comprising repeating steps a) and b).

[0316] Embodiment 44. The method according to Embodiment 43, wherein steps a) and b) are cycled for at least about one week.

[0317] Embodiment 45. The method according to Embodiment 43, wherein steps a) and b) are cycled for at least about one month.

[0318] Embodiment 46. The method according to any one of Embodiments 39-45, wherein the average serum amino acid level is reduced by at least about 30%.

[0319] Embodiment 47. The method according to any one of Embodiments 39-34, wherein the average serum amino acid level is reduced by at least about 50%.

[0320] Embodiment 48. The method according to any one of Embodiments 39-47, wherein the reduced average serum amino acid level persists during the second time period.

[0321] Embodiment 49. The method according to any one of Embodiments 35-48, wherein the modified diet provides at least about 50% of the daily calories from fat.

[0322] Embodiment 50. The method according to any one of Embodiments 35-48, wherein the modified diet provides at least about 80% of the daily calories from fat.

[0323] Embodiment 51. Embodiment 31. The method according to any one of Embodiments 35-50, wherein the modified diet provides up to about 30% of the daily calories from carbohydrates.

[0324] Embodiment 52. The method according to any one of Embodiments 35-50, wherein the modified diet provides up to about 15% of the daily calories from carbohydrates.

[0325] Embodiment 53. The method according to any one of embodiments 35-52, wherein the modified diet provides up to about 10 g of protein per day.

[0326] Embodiment 54. The method according to any one of embodiments 35-52, wherein the modified diet provides up to about 9 g of protein per day.

[0327] Embodiment 55. The method according to any one of embodiments 35-54, wherein the modified diet provides up to about 500 mg per day of the at least one non-essential amino acid.

[0328] Embodiment 56. The method according to any one of embodiments 35-55, wherein the modified diet provides up to about 500 mg per day of serine.

[0329] Embodiment 57. The method according to any one of embodiments 35-55, wherein the modified diet provides up to about 500 mg per day of glycine. Specification 81 / 87 pages 83 CN 121445725 A

[0330] Embodiment 58. The method according to any one of embodiments 33-57, wherein the administration is oral.

[0331] Embodiment 59. The method according to any one of Embodiments 33-58, wherein the dietary product is applied three times daily.

[0332] Embodiment 60. The method according to any one of Embodiments 33-59, wherein the dietary product is applied four times daily.

[0333] Embodiment 61. The method according to any one of Embodiments 33-60, wherein the therapeutically effective amount of the dietary product is about 0.5 g / kg / day to about 1 g / kg / day.

[0334] Embodiment 62. The method according to Embodiment 61, wherein the therapeutically effective amount of the dietary product is about 0.8 g / kg / day.

[0335] Embodiment 63. The method according to any one of Embodiments 33-62, wherein the dietary product further comprises about 2% to about 5% of a K+ source.

[0336] Embodiment 64. The method according to Embodiment 63, wherein the K+ source is potassium chloride.

[0337] Embodiment 65. The method according to Embodiment 63, wherein the K+ source is potassium aspartate, and the aspartic acid, its hydrate, or its hydrate is a free aspartic acid base.

[0338] Embodiment 66. The method according to any one of Embodiments 33-65, wherein the dietary product further comprises about 1% to about 4% (w / w) of a Mg2+ source.

[0339] Embodiment 67. The method according to Embodiment 66, wherein the Mg2+ source is magnesium citrate.

[0340] Embodiment 68. The method according to Embodiment 66, wherein the Mg2+ source is magnesium aspartate, and the aspartic acid, its hydrate, or its salt is a free aspartic acid acid.

[0341] Embodiment 69. The method according to any one of Embodiments 33-68, wherein the dietary product further comprises about 0.05% to about 2% (w / w) taurine, its hydrate or a salt thereof.

[0342] Embodiment 70. The method according to any one of Embodiments 33-69, wherein the dietary product further comprises glucose.

[0343] Embodiment 71. The method according to any one of Embodiments 33-70, wherein the at least one non-essential amino acid is proline.

[0344] Embodiment 72. The method according to any one of Embodiments 33-70, wherein the at least one non-essential amino acid is serine.

[0345] Embodiment 73. The method according to any one of Embodiments 33-70, wherein the at least one non-essential amino acid is glycine.

[0346] Embodiment 74. The method according to any one of Embodiments 33-70, wherein the at least one non-essential amino acid is glutamate.

[0347] Embodiment 75. The method according to any one of Embodiments 33-70, wherein the at least one non-essential amino acid is glutamine.

[0348] Embodiment 76. The method according to any one of Embodiments 33-70, wherein the at least one non-essential amino acid is cysteine.

[0349] Embodiment 77. The method according to any one of Embodiments 33-70, wherein the at least one non-essential amino acid is asparagine.

[0350] Embodiment 78. The method according to any one of Embodiments 33-70, wherein the dietary product does not contain serine or glycine. Specification 82 / 87 pages 84 CN 121445725 A

[0351] Embodiment 79. The method according to any one of Embodiments 33-70, wherein the dietary product does not contain serine, glycine, or proline.

[0352] Embodiment 80. The method according to any one of Embodiments 33-70, wherein the dietary product does not contain serine, glycine, or cysteine.

[0353] Embodiment 81. The method according to any one of Embodiments 33-70, wherein the dietary product does not contain serine, glycine, proline, or cysteine.

[0354] Embodiment 82. The method according to any one of Embodiments 33-70, wherein the dietary product does not contain serine, glycine, proline, or tyrosine.

[0355] Embodiment 83. The method according to any one of Embodiments 33-70, wherein the dietary product does not contain serine, glycine, proline, or arginine.

[0356] Embodiment 84. The method according to any one of Embodiments 33-70, wherein the dietary product does not contain serine, glycine, proline, cysteine, or tyrosine.

[0357] Embodiment 85. The method according to any one of Embodiments 33-70, wherein the dietary product does not contain serine, glycine, proline, cysteine, or arginine.

[0358] Embodiment 86. The method according to any one of Embodiments 33-70, wherein the dietary product does not contain serine, glycine, proline, cysteine, tyrosine, or arginine.

[0359] Embodiment 87. The method according to any one of Embodiments 33-70, wherein the dietary product does not contain serine, glycine, glutamic acid, glutamine, or cysteine.

[0360] Embodiment 88. The method according to any one of Embodiments 33-87, further comprising administering a therapeutic agent.

[0361] Embodiment 89. The method according to Embodiment 88, wherein the therapeutic agent is a chemotherapeutic agent.

[0362] Embodiment 90. The method according to Embodiment 88, wherein the therapeutic agent is a radiotherapy agent.

[0363] Embodiment 91. The method according to Embodiment 88, wherein the therapeutic agent is immunotherapy.

[0364] Embodiment 100. A composition comprising, in unit dosage form: a) about 2% to about 6% (w / w) histidine or a salt thereof; b) about 2% to about 6% (w / w) isoleucine or a salt thereof; c) about 6% to about 11% (w / w) leucine or a salt thereof; d) about 5% to about 9% (w / w) lysine or a salt thereof; e) about 2% to about 4% (w / w) methionine or a salt thereof; f) about 1% to about 3% (w / w) cysteine ​​or a salt thereof; g) about 3% to about 6% (w / w) phenylalanine or a salt thereof; h) about 1% to about 3% (w / w) tyrosine or a salt thereof; i) about 3% to about 5% (w / w) threonine or a salt thereof; j) about 1% to about 3% (w / w) tryptophan or a salt thereof; k) about 5% to about 9% (w / w) valine or a salt thereof; l) about 5% to about 9% (w / w) arginine or a salt thereof; m) about 5% to about 11% (w / w) glutamine or a salt thereof; n) about 2% to about 7% (w / w) alanine or a salt thereof; o) about 6% to about 10% (w / w) aspartic acid or a salt thereof; p) about 3% to about 7% (w / w) asparagine or a salt thereof; q) about 8% to about 14% (w / w) glutamic acid or a salt thereof; and r) about 6% to about 12% (w / w) proline or a salt thereof.

[0365] Embodiment 102. A composition comprising, in unit dosage form: a) about 5% to about 9% (w / w) histidine or a salt thereof; b) about 5% to about 9% (w / w) isoleucine or a salt thereof; c) about 9% to about 15% (w / w) leucine or a salt thereof; d) about 7% to about 12% (w / w) lysine or a salt thereof; e) about 5% to about 8%f) about 4% to about 7% (w / w) methionine or a salt thereof; g) about 6% to about 10% (w / w) phenylalanine or a salt thereof; h) about 4% to about 7% (w / w) tyrosine or a salt thereof; i) about 6% to about 10% (w / w) threonine or a salt thereof; j) about 4% to about 7% (w / w) tryptophan or a salt thereof; k) about 8% to about 13% (w / w) valine or a salt thereof; l) about 5% to about 9% (w / w) arginine or a salt thereof; and m) about 7% to about 11% (w / w) glutamine or a salt thereof.

[0366] Embodiment 103. A composition comprising, in unit dosage form: a) about 2% to about 5% (w / w) histidine or its salt; b) about 2% to about 5% (w / w) isoleucine or its salt; c) about 6% to about 10% (w / w) leucine or its salt; d) about 5% to about 8% (w / w) lysine or its salt; e) about 2% to about 4% (w / w) methionine or its salt; f) about 1% to about 3% (w / w) cysteine ​​or its salt; g) about 3% to about 5% (w / w) phenylalanine or its salt; h) about 1% to about 3% (w / w) tyrosine or its salt; i) about 3% to about 5% (w / w) threonine or its salt; j) about 1% to about 3% k) about 5% to about 9% (w / w) of tryptophan or a salt thereof; l) about 5% to about 9% (w / w) of arginine or a salt thereof; m) about 7% to about 11% (w / w) of glutamine or a salt thereof; n) about 4% to about 7% (w / w) of alanine or a salt thereof; o) about 6% to about 10% (w / w) of aspartic acid or a salt thereof; p) about 3% to about 6% (w / w) of asparagine or a salt thereof; q) about 8% to about 14% (w / w) of glutamic acid or a salt thereof; and r) about 6% to about 10% (w / w) of proline or a salt thereof, wherein, if in a study of changes in tumor volume of the subjects, the tumor volume of the subjects receiving the composition was reduced by at least about 20% compared with that of the subjects receiving placebo.

[0367] Embodiment 104. The composition according to Embodiment 101 or 103, wherein the salts of histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, threonine, tryptophan, valine, arginine, glutamine, alanine, aspartic acid, asparagine, glutamic acid, and proline are pharmaceutically acceptable salts.

[0368] Embodiment 105. A composition comprising, in unit dosage form: a) about 5% to about 9% (w / w) histidine or a salt thereof; b) about 5% to about 9% (w / w) isoleucine or a salt thereof; c) about 9% to about 15%...d) leucine or a salt thereof (w / w); d) about 7% to about 12% (w / w) lysine or a salt thereof; e) about 5% to about 8% (w / w) methionine or a salt thereof; f) about 4% to about 7% (w / w) cysteine ​​or a salt thereof; g) about 6% to about 10% (w / w) phenylalanine or a salt thereof; h) about 4% to about 7% (w / w) tyrosine or a salt thereof; i) about 6% to about 10% (w / w) threonine or a salt thereof; j) about 4% to about 7% (w / w) tryptophan or a salt thereof; k) about 8% to about 13% (w / w) valine or a salt thereof; l) about 5% to about 9% (w / w) arginine or a salt thereof; and m) about 7% to about 11% (w / w) glutamine or a salt thereof, wherein, if a comparative study is conducted, wherein the comparative study includes administration of the composition to a first subject and administration of a placebo to a second subject, the tumor volume of the first subject is reduced compared to the tumor volume of the second subject.

[0369] Embodiment 106. The composition according to Embodiment 102 or 105, wherein the salts of histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, threonine, tryptophan, valine, arginine, and glutamine are pharmaceutically acceptable salts.

[0370] Embodiment 107. A composition comprising, in unit dosage form: a) about 3% to about 7% (w / w) histidine, its hydrate or a salt thereof; b) about 3% to about 6% (w / w) isoleucine, its hydrate or a salt thereof; c) about 7% to about 11% (w / w) leucine, its hydrate or a salt thereof; d) about 5% to about 9% (w / w) lysine, its hydrate or a salt thereof; e) about 2% to about 4% (w / w) methionine, its hydrate or a salt thereof; f) about 1% to about 3% (w / w) cysteine, its hydrate or a salt thereof; g) about 3% to about 7% (w / w) phenylalanine, its hydrate or a salt thereof; h) about 1% to about 3% (w / w) tyrosine, its hydrate or a salt thereof; i) about 2% to about 5% (w / w) threonine, its hydrate or a salt thereof; j) about 1% to about 3% (w / w) tryptophan, its hydrate or salt thereof; (k) about 5% to about 9% (w / w) valine, its hydrate or salt thereof; (l) about 5% to about 9% (w / w) arginine, its hydrate or salt thereof; (m) about 7% to about 11% (w / w) glutamine, its hydrate or salt thereof; (n) about 3% to about 7% (w / w) alanine, its hydrate or salt thereof; (o) about 6% to about 10% (w / w) aspartic acid, its hydrate or salt thereof; (p) about 3% to about 6% (w / w) asparagine, its hydrate or salt thereof; (q) about 8% to about 14% (w / w) glutamic acid, its hydrate or salt thereof; (r) about 2% to about 5%(w / w) serine, its hydrate or salt thereof; and (s) about 3% to about 7% (w / w) glycine, its hydrate or salt thereof.

[0371] Embodiment 108. The composition according to Embodiment 107, wherein the salts of histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, threonine, tryptophan, valine, arginine, glutamic acid, alanine, aspartic acid, asparagine, glutamic acid, serine and glycine are pharmaceutically acceptable salts.

[0372] Embodiment 109. A composition comprising, in unit dosage form: a) about 3% to about 7% (w / w) histidine, its hydrate or a salt thereof; b) about 4% to about 8% (w / w) isoleucine, its hydrate or a salt thereof; c) about 9% to about 13% (w / w) leucine, its hydrate or a salt thereof; d) about 8% to about 12% (w / w) lysine, its hydrate or a salt thereof; e) about 1% to about 4% (w / w) methionine, its hydrate or a salt thereof; f) about 1% to about 4% (w / w) cysteine, its hydrate or a salt thereof; g) about 5% to about 9% (w / w) phenylalanine, its hydrate or a salt thereof; h) about 1% to about 5% (w / w) tyrosine, its hydrate or a salt thereof; i) about 4% to about 8% (w / w) threonine, its hydrate or a salt thereof; j) about 1% to about 4% (w / w) tryptophan, its hydrate or salt thereof; (k) about 5% to about 10% (w / w) valine, its hydrate or salt thereof; (l) about 1% to about 10% (w / w) arginine, its hydrate or salt thereof; (m) about 1% to about 5% (w / w) glutamine, its hydrate or salt thereof; (n) about 4% to about 8% (w / w) alanine, its hydrate or salt thereof; (o) about 4% to about 12% (w / w) aspartic acid, its hydrate, acid or salt thereof; (p) about 4% to about 8% (w / w) asparagine, its hydrate or salt thereof; and (q) about 5% to about 15% (w / w) glutamic acid, its hydrate or salt thereof.

[0373] Embodiment 110. A composition comprising, in unit dosage form: a) about 4% to about 6% (w / w) histidine, its hydrate or a salt thereof; b) about 5% to about 7% (w / w) isoleucine, its hydrate or a salt thereof; c) about 9% to about 12% (w / w) leucine, its hydrate or a salt thereof; d) about 8% to about 12% (w / w) lysine, its hydrate or a salt thereof; e) about 1% to about 4% (w / w) methionine, its hydrate or a salt thereof; f) about 1% to about 3% (w / w) cysteine, its hydrate or a salt thereof; g) about 6% to about 8% (w / w) phenylalanine, its hydrate or a salt thereof; h) about 1% to about 4%(w / w) tyrosine, its hydrate or salt thereof; i) about 4% to about 7% (w / w) threonine, its hydrate or salt thereof; j) about 1% to about 3% (w / w) tryptophan, its hydrate or salt thereof; k) about 4% to about 9% (w / w) valine, its hydrate or salt thereof; l) about 7% to about 11% (w / w) arginine, its hydrate or salt thereof; m) about 2% to about 4% (w / w) glutamine, its hydrate or salt thereof; n) about 4% to about 7% (w / w) alanine, its hydrate or salt thereof; o) about 8% to about 11% (w / w) aspartic acid, its hydrate or salt thereof; p) about 4% to about 7% (w / w) asparagine, its hydrate or salt thereof; and q) about 4% to about 8% (w / w) glutamic acid, its hydrate or salt thereof.

[0374] Embodiment 111. The composition according to Embodiment 109 or 110, wherein the salts of histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, threonine, tryptophan, valine, arginine, glutamine, alanine, aspartic acid, asparagine and glutamic acid are pharmaceutically acceptable salts.

[0375] Embodiment 112. A composition comprising, in unit dosage form: a) about 4% to about 6% (w / w) histidine, its hydrate or a salt thereof; b) about 5% to about 7% (w / w) isoleucine, its hydrate or a salt thereof; c) about 11% to about 13% (w / w) leucine, its hydrate or a salt thereof; d) about 8% to about 10% (w / w) lysine, its hydrate or a salt thereof; e) about 2% to about 4% (w / w) methionine, its hydrate or a salt thereof; f) about 6% to about 8% (w / w) phenylalanine, its hydrate or a salt thereof; g) about 1% to about 3% (w / w) tyrosine, its hydrate or a salt thereof; h) about 3% to about 5% (w / w) threonine, its hydrate or a salt thereof; i) about 1% to about 3% (w / w) tryptophan, its hydrate or a salt thereof; j) about 8% to about 10% (w / w) valine, its hydrate or salt thereof; (k) about 7% to about 9% (w / w) arginine, its hydrate or salt thereof; (l) about 3% to about 5% (w / w) alanine, its hydrate or salt thereof; (m) about 4% to about 6% (w / w) aspartic acid, its hydrate or salt thereof; (n) about 4% to about 7% (w / w) asparagine, its hydrate or salt thereof; and (o) about 14% to about 17% (w / w) proline, its hydrate or salt thereof.

[0376] Embodiment 113. The composition according to Embodiment 112, wherein the salts of histidine, isoleucine, leucine, lysine, methionine, phenylalanine, tyrosine, threonine, tryptophan, valine, arginine, alanine, aspartic acid, asparagine and proline are pharmaceutically acceptable salts. (Instructions for Use)Pages 85 / 87 CN 121445725 A

[0377] Embodiment 114. A composition comprising, in unit dosage form: a) about 3% to about 5% (w / w) histidine, its hydrate or a salt thereof; b) about 5% to about 7% (w / w) isoleucine, its hydrate or a salt thereof; c) about 10% to about 12% (w / w) leucine, its hydrate or a salt thereof; d) about 9% to about 11% (w / w) lysine, its hydrate or a salt thereof; e) about 2% to about 4% (w / w) methionine, its hydrate or a salt thereof; f) about 9% to about 11% (w / w) proline, its hydrate or a salt thereof; g) about 6% to about 8% (w / w) phenylalanine, its hydrate or a salt thereof; h) about 1% to about 4% (w / w) tyrosine, its hydrate or a salt thereof; i) about 5% to about 7% (w / w) threonine, its hydrate or salt thereof; (j) about 1% to about 3% (w / w) tryptophan, its hydrate or salt thereof; (k) about 5% to about 7% (w / w) valine, its hydrate or salt thereof; (l) about 1% to about 3% (w / w) arginine, its hydrate or salt thereof; (m) about 2% to about 4% (w / w) glutamine, its hydrate or salt thereof; (n) about 5% to about 7% (w / w) alanine, its hydrate or salt thereof; (o) about 4% to about 12% (w / w) aspartic acid, its hydrate or salt thereof; (p) about 5% to about 7% (w / w) asparagine, its hydrate or salt thereof; and (q) about 4% to about 12% (w / w) glutamic acid, its hydrate or salt thereof.

[0378] Embodiment 115. The composition according to Embodiment 114, wherein the salts of histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, tyrosine, threonine, tryptophan, valine, arginine, glutamine, alanine, aspartic acid, asparagine, and glutamic acid are pharmaceutically acceptable salts.

[0379] Embodiment 116. The composition according to any one of Embodiments 100-115, wherein the composition is a pharmaceutical composition.

[0380] Embodiment 117. The composition according to any one of Embodiments 100-115, wherein the composition is a medical food.

[0381] Embodiment 118. The composition according to any one of Embodiments 100-115, wherein the composition is a nutritional supplement.

[0382] Embodiment 119. The composition according to any one of Embodiments 100-118, wherein the weight of the unit dosage form is about 12 grams.

[0383] Embodiment 120. The composition according to any one of Embodiments 100-119, wherein the composition is in powder form.

[0384] Embodiment 121. The composition according to any one of embodiments 100-120, further comprising a preservative.

[0385] Embodiment 122. The composition according to any one of embodiments 100-121, further comprising a pharmaceutically acceptable excipient.

[0386] Embodiment 123. The composition according to any one of embodiments 100-122, further comprising a flavoring agent.

[0387] Embodiment 124. The composition according to any one of embodiments 100-123, wherein the composition further comprises about 0.05% to about 2% (w / w) of taurine, its hydrate or a salt thereof.

[0388] Embodiment 125. The composition according to any one of embodiments 100-124, wherein the composition further comprises about 1% to about 4% (w / w) of a Mg2+ source.

[0389] Embodiment 126. The composition according to Embodiment 125, wherein the Mg2+ source comprises magnesium citrate, magnesium fumarate, magnesium acetate, magnesium aspartate, magnesium threonate, magnesium glycine, magnesium chloride, magnesium sulfate, magnesium oxide, or magnesium malate, magnesium orotate, or their hydrates.

[0390] Embodiment 127. The composition according to Embodiment 125, wherein the Mg2+ source is magnesium citrate.

[0391] Embodiment 128. The composition according to Embodiment 125, wherein the Mg2+ source is magnesium aspartate, and the aspartic acid, its hydrate, or its salt is an aspartic acid free acid.

[0392] Embodiment 129. The composition according to any one of Embodiments 100-128, wherein the composition further comprises about 2% to about 5% of a K+ source.

[0393] Embodiment 130. The composition according to Embodiment 129, wherein the K+ source comprises potassium citrate, potassium phosphate, potassium chloride, potassium sulfate, potassium gluconate, potassium bicarbonate, potassium aspartate, potassium acetate, and potassium orotate.

[0394] Embodiment 131. The composition according to Embodiment 129, wherein the K+ source is potassium chloride.

[0395] Embodiment 132. The composition according to Embodiment 129, wherein the K+ source is potassium aspartate, and the aspartic acid, its hydrate, or its hydrate is a free aspartic acid base.

[0396] Embodiment 133. The composition according to any one of Embodiments 100-132, wherein the histidine, its hydrate, or its salt is histidine hydrochloride.

[0397] Embodiment 134. The composition according to any one of Embodiments 100-132, wherein the lysine, its hydrate, or its salt is lysine hydrochloride.

[0398] Embodiment 135. The composition according to any one of embodiments 100-134, wherein the lysine, its hydrate, or its salt is lysine monohydrate.

[0399] Embodiment 136. The composition according to any one of embodiments 100-111 or 116-135, wherein the cysteine, its hydrate, or its salt is cysteine ​​hydrochloride.

[0400] Embodiment 137. The composition according to any one of embodiments 100 or 116-136, wherein the asparagine, its hydrate, or its salt is asparagine hydrate.

[0401] Embodiment 138. The composition according to any one of embodiments 100-104 or 107-137, wherein the glutamic acid, its hydrate, or its salt is arginine glutamate, and the arginine is arginine free base. Instruction manual page 87 / 87, page 89, CN 121445725 A, Figure 1; Instruction manual figure 1 / 13, page 90, CN 121445725 A, Figure 2; Instruction manual figure 2 / 13, page 91, CN 121445725 A, Figure 3; Instruction manual figure 3 / 13, page 92, CN 121445725 A, Figure 4; Instruction manual figure 4 / 13, page 93, CN 121445725 A, Figure 5; Instruction manual figure 5 / 13, page 94, CN 121445725 A, Figure 6; Instruction manual figure 6 / 13, page 95, CN 121445725 A, Figure 7; Instruction manual figure 7 / 13, page 96, CN 121445725 A, Figure 8; Instruction manual figure 8 / 13, page 97, CN 121445725 A, Figure 9; Instruction manual figure 9 / 13, page 98, CN 121445725 A, Figure 10. Figure 11 (Page 10 / 13, CN 121445725 A) Figure 12 (Page 12 / 13, CN 121445725 A) Figure 13 (Page 13 / 13, CN 121445725 A) Abstract: The present application relates to formulations for personalized methods of treatment. Disclosed herein are formulations and methods ofadministering formulations to starve cells of nutrients, such as amino acids. The formulations of the present invention can be substantially be devoid of one or more non-essential amino acids. Disclosed herein is a composition which is in a unit dosage form comprising: a) non-essential amino acids or salts thereof, wherein said non-essential amino acids or the salts thereof are not part of a polypeptide; b) a first essential amino acid or a first salt thereof and a second essential amino acid or a second salt thereof, wherein the first essential amino acid or the first salt thereof and the second essential amino acid or the second salt thereof are present in the composition in equal amounts, wherein the first essential amino acid and the first salt thereof as well as the second essential amino acid and the second salt thereof are not part of a polypeptide; and c) a pharmaceutically acceptable excipient.

Claims

1. A composition comprising, in unit dosage form: a) A non-essential amino acid or its salt, wherein the non-essential amino acid or its salt is not part of a polypeptide; b) A first essential amino acid or its first salt and a second essential amino acid or its second salt, wherein the first essential amino acid or its first salt and the second essential amino acid or its second salt are present in the composition in equal amounts, wherein the first essential amino acid and its first salt, and the second essential amino acid and its second salt, are not part of a polypeptide; and c) Pharmaceutically acceptable excipients.

2. The composition according to claim 1, wherein the first essential amino acid or the first salt thereof is histidine, and the second essential amino acid or the second salt thereof is isoleucine.

3. The composition according to claim 1, wherein the first essential amino acid and the second essential amino acid are present in the composition in an amount of about 2% to about 6% (w / w).

4. The composition according to claim 1, further comprising a third essential amino acid, wherein the third essential amino acid is present in the composition in an amount different from that of the first essential amino acid and the second essential amino acid.

5. The composition according to claim 1, wherein the composition does not contain at least one non-essential amino acid.

6. The composition according to claim 1, wherein the composition is free of at least serine and glycine.

7. The composition according to claim 1, wherein the composition is at least free of proline.

8. The composition according to claim 1, wherein the composition is at least free of cysteine.

9. The composition according to claim 1, wherein the weight of the unit dosage form is about 12 grams.

10. The composition according to claim 1, wherein the composition is in powder form.

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