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EP-4736862-A1 - COMPOSITION PROVIDING IMPROVED ORAL BIOAVAILABILITY OF DRUG AND METHOD THEREFOR

EP4736862A1EP 4736862 A1EP4736862 A1EP 4736862A1EP-4736862-A1

Abstract

A composition providing improved oral bioavailability of a drug and a method therefor. Also disclosed is the use of a delivery synergist in the improvement of the oral bioavailability of a protein or polypeptide drug. When the delivery synergist is added to the pharmaceutical composition at a certain ratio relative to a delivery agent, the delivery effect of the delivery agent can be maximized, which can not only reduce the use amount of the delivery agent, but can also improve the oral bioavailability of the drug.

Inventors

  • WANG, HONGYANG
  • JIANG, Shiyue
  • GUO, Wanjun
  • PAN, HAI

Assignees

  • Hang Zhou Sciwind Biosciences Co., Ltd.
  • Sciwind Biosciences (Beijing) Co., Ltd.

Dates

Publication Date
20260506
Application Date
20240412

Claims (17)

  1. Use of a delivery synergist in improving the oral bioavailability of a protein or polypeptide drug, wherein the protein or polypeptide drug is used in combination with the delivery synergist, and the delivery synergist comprises hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, sucralfate, calcium bicarbonate, aluminum bicarbonate, magnesium bicarbonate, and/or magnesium hydroxide; the protein or polypeptide drug is delivered by a delivery agent; preferably, the delivery synergist comprises hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, and/or sucralfate.
  2. The use according to claim 1, wherein the protein or polypeptide drug comprises a hormone, a growth factor, a cytokine, an analgesic peptide, an enzyme, a coagulation factor, a peptide neurotransmitter, and/or an antibody.
  3. The use according to claim 1, wherein the protein or polypeptide drug comprises a receptor agonist or antagonist; preferably, the receptor agonist or antagonist comprises a GLP-1 receptor agonist, a GLP-1 receptor antagonist, a GIP receptor agonist, a GIP receptor antagonist, and/or an insulin receptor agonist; preferably, the receptor agonist or antagonist comprises a GLP-1 receptor agonist; preferably, the GLP-1 receptor agonist comprises an exendin, GLP-1 or an analog, fragment, derivative, fusion protein, or conjugate thereof, or a pharmaceutically acceptable salt of the molecule described above; preferably, the GLP-1 receptor agonist has a structure represented by formula (I):
  4. The use according to any one of claims 1-3, wherein the delivery agent has a structure represented by formula (III): in formula (III), L represents linear or branched C5-C11 alkylene, and M represents Na + , K + , or NH 4 + ; preferably, L represents linear or branched C7-C9 alkylene, and M represents K + ; preferably, the delivery agent comprises a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; preferably, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid comprises a sodium salt, a potassium salt, and/or an ammonium salt; preferably, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is selected from a potassium salt, which has a structure represented by formula (II): or the delivery agent has a structure represented by formula (IV): CH 3 -(CH 2 )n-COOM, (IV) in formula (IV), n represents an integer from 4 to 10, and M represents Na + , K + , or NH 4 + ; preferably, n represents an integer from 6 to 8, and M represents Na + ; preferably, the delivery agent comprises a salt of caprylic acid, capric acid, and/or lauric acid; preferably, the delivery agent comprises a sodium salt, a potassium salt, and/or an ammonium salt of caprylic acid, capric acid, and/or lauric acid; or the delivery agent comprises a salt of chenodeoxycholic acid; preferably, the delivery agent comprises a sodium salt, a potassium salt, and/or an ammonium salt of chenodeoxycholic acid; preferably, the delivery agent and the delivery synergist are in a mass ratio of 1:0.3-1:3; preferably, the delivery agent and the delivery synergist are in a mass ratio of 1:0.3-1:2; preferably, the combination use comprises simultaneously using the protein or polypeptide drug and the delivery synergist in the form of a pharmaceutical composition; or separately using the protein or polypeptide drug and the delivery synergist in sequence; preferably, the combination use is to simultaneously use the protein or polypeptide drug and the delivery synergist in the form of a pharmaceutical composition; preferably, the protein or polypeptide drug and the delivery agent are in a mass ratio of 1:5-1:150; preferably, the protein or polypeptide drug and the delivery agent are in a mass ratio of 1:10-1:50; preferably, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier; preferably, the pharmaceutically acceptable carrier comprises a lubricant, a filler, a disintegrant, a flavoring agent, a colorant, a binder, an forming agent, a buffer, a diluent, a solubilizer, a tonicity regulator, a surfactant, a preservative, an isotonic agent, a stabilizer, and/or a chelating agent; preferably, the pharmaceutically acceptable carrier comprises a lubricant, a filler, and a disintegrant; preferably, the lubricant comprises magnesium stearate, glyceryl tribehenate, and/or stearic acid; preferably, the lubricant is selected from magnesium stearate; preferably, the filler is selected from mannitol and/or microcrystalline cellulose; preferably, the disintegrant is selected from croscarmellose sodium; preferably, the pharmaceutical composition further comprises one or more active pharmaceutical ingredients for use in combination with the protein or polypeptide drug; preferably, the active pharmaceutical ingredient is selected from an antidiabetic agent, an anti-obesity agent, an appetite-regulating agent, an antihypertensive agent, an agent for treating and/or preventing complications and conditions caused by or associated with diabetes, and an agent for treating and/or preventing complications and conditions caused by or associated with obesity; preferably, a dosage form of the pharmaceutical composition comprises a tablet, a capsule, an emulsion, an aqueous suspension, a dispersant, or a powder; preferably, the dosage form of the pharmaceutical composition is a tablet; preferably, the tablet is prepared by a dry granulation process and/or a direct mixing process; preferably, the tablet has a hardness of 30-90 N.
  5. A method for improving the oral bioavailability of a protein or polypeptide drug, comprising: using the protein or polypeptide drug in combination with a delivery synergist, wherein the delivery synergist comprises hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, sucralfate, calcium bicarbonate, aluminum bicarbonate, magnesium bicarbonate, and/or magnesium hydroxide; the protein or polypeptide drug is delivered by a delivery agent; preferably, the delivery synergist comprises hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, and/or sucralfate.
  6. The method according to claim 5, wherein the protein or polypeptide drug comprises a hormone, a growth factor, a cytokine, an analgesic peptide, an enzyme, a coagulation factor, a peptide neurotransmitter, and/or an antibody.
  7. The method according to claim 5, wherein the protein or polypeptide drug comprises a receptor agonist or antagonist; preferably, the receptor agonist or antagonist comprises a GLP-1 receptor agonist, a GLP-1 receptor antagonist, a GIP receptor agonist, a GIP receptor antagonist, and/or an insulin receptor agonist; preferably, the receptor agonist or antagonist comprises a GLP-1 receptor agonist; preferably, the GLP-1 receptor agonist comprises an exendin, GLP-1 or an analog, fragment, derivative, fusion protein, or conjugate thereof, or a pharmaceutically acceptable salt of the molecule described above; preferably, the GLP-1 receptor agonist has a structure represented by formula (I):
  8. The method according to any one of claims 5-7, wherein the combination use comprises simultaneously using the protein or polypeptide drug and the delivery synergist in the form of a pharmaceutical composition; or separately using the protein or polypeptide drug and the delivery synergist in sequence; preferably, the combination use is to simultaneously use the protein or polypeptide drug and the delivery synergist in the form of a pharmaceutical composition; preferably, a dosage form of the pharmaceutical composition comprises a tablet, a capsule, an emulsion, an aqueous suspension, a dispersant, or a powder; preferably, the dosage form of the pharmaceutical composition is a tablet; preferably, the tablet is prepared by a dry granulation process and/or a direct mixing process; preferably, the tablet has a hardness of 30-90 N.
  9. The method according to any one of claims 5-8, wherein the delivery agent has a structure represented by formula (III): in formula (III), L represents linear or branched C5-C11 alkylene, and M represents Na + , K + , or NH 4 + ; preferably, L represents linear or branched C7-C9 alkylene, and M represents K + ; preferably, the delivery agent comprises a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; preferably, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid comprises a sodium salt, a potassium salt, and/or an ammonium salt; preferably, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is selected from a potassium salt, which has a structure represented by formula (II): or the delivery agent has a structure represented by formula (IV): CH 3 -(CH 2 )n-COOM, (IV) in formula (IV), n represents an integer from 4 to 10, and M represents Na + , K + , or NH 4 + ; preferably, n represents an integer from 6 to 8, and M represents Na + ; preferably, the delivery agent comprises a salt of caprylic acid, capric acid, and/or lauric acid; preferably, the delivery agent comprises a sodium salt, a potassium salt, and/or an ammonium salt of caprylic acid, capric acid, and/or lauric acid; or the delivery agent comprises a salt of chenodeoxycholic acid; preferably, the delivery agent comprises a sodium salt, a potassium salt, and/or an ammonium salt of chenodeoxycholic acid; preferably, the delivery agent and the delivery synergist are in a mass ratio of 1:0.3-1:3; preferably, the delivery agent and the delivery synergist are in a mass ratio of 1:0.3-1:2; preferably, the protein or polypeptide drug and the delivery agent are in a mass ratio of 1:5-1:150; preferably, the protein or polypeptide drug and the delivery agent are in a mass ratio of 1:10-1:50.
  10. The method according to claim 8, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier; preferably, the pharmaceutically acceptable carrier comprises a lubricant, a filler, a disintegrant, a flavoring agent, a colorant, a binder, an forming agent, a buffer, a diluent, a solubilizer, a tonicity regulator, a surfactant, a preservative, an isotonic agent, a stabilizer, and/or a chelating agent; preferably, the pharmaceutically acceptable carrier comprises a lubricant, a filler, and a disintegrant; preferably, the lubricant comprises magnesium stearate, glyceryl tribehenate, and/or stearic acid; preferably, the lubricant is selected from magnesium stearate; preferably, the filler is selected from mannitol and/or microcrystalline cellulose; preferably, the disintegrant is selected from croscarmellose sodium; preferably, the pharmaceutical composition further comprises one or more active pharmaceutical ingredients for use in combination with the protein or polypeptide drug; preferably, the active pharmaceutical ingredient is selected from an antidiabetic agent, an anti-obesity agent, an appetite-regulating agent, an antihypertensive agent, an agent for treating and/or preventing complications and conditions caused by or associated with diabetes, and an agent for treating and/or preventing complications and conditions caused by or associated with obesity.
  11. A pharmaceutical composition having improved oral bioavailability and having a protein or polypeptide drug as an active ingredient, comprising a delivery synergist, wherein the delivery synergist comprises hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, sucralfate, calcium bicarbonate, aluminum bicarbonate, magnesium bicarbonate, and/or magnesium hydroxide; the pharmaceutical composition further comprises a delivery agent; preferably, the delivery synergist comprises hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, and/or sucralfate; preferably, the protein or polypeptide drug comprises a hormone, a growth factor, a cytokine, an analgesic peptide, an enzyme, a coagulation factor, a peptide neurotransmitter, and/or an antibody; or the protein or polypeptide drug comprises a receptor agonist or antagonist; preferably, the receptor agonist or antagonist comprises a GLP-1 receptor agonist, a GLP-1 receptor antagonist, a GIP receptor agonist, a GIP receptor antagonist, and/or an insulin receptor agonist; preferably, the receptor agonist or antagonist comprises a GLP-1 receptor agonist; preferably, the GLP-1 receptor agonist comprises an exendin, GLP-1 or an analog, fragment, derivative, fusion protein, or conjugate thereof, or a pharmaceutically acceptable salt of the molecule described above; preferably, the GLP-1 receptor agonist has a structure represented by formula (I): preferably, the delivery agent has a structure represented by formula (III): in formula (III), L represents linear or branched C5-C11 alkylene, and M represents Na + , K + , or NH 4 + ; preferably, L represents linear or branched C7-C9 alkylene, and M represents K + ; preferably, the delivery agent comprises a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; preferably, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid comprises a sodium salt, a potassium salt, and/or an ammonium salt; preferably, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is selected from a potassium salt, which has a structure represented by formula (II): or the delivery agent has a structure represented by formula (IV): CH 3 -(CH 2 )n-COOM, (IV) in formula (IV), n represents an integer from 4 to 10, and M represents Na + , K + , or NH 4 + ; preferably, n represents an integer from 6 to 8, and M represents Na + ; preferably, the delivery agent comprises a salt of caprylic acid, capric acid, and/or lauric acid; preferably, the delivery agent comprises a sodium salt, a potassium salt, and/or an ammonium salt of caprylic acid, capric acid, and/or lauric acid; or the delivery agent comprises a salt of chenodeoxycholic acid; preferably, the delivery agent comprises a sodium salt, a potassium salt, and/or an ammonium salt of chenodeoxycholic acid; preferably, the delivery agent and the delivery synergist are in a mass ratio of 1:0.3-1:3; preferably, the delivery agent and the delivery synergist are in a mass ratio of 1:0.3-1:2; preferably, the protein or polypeptide drug and the delivery agent are in a mass ratio of 1:5-1:150; preferably, the protein or polypeptide drug and the delivery agent are in a mass ratio of 1:10-1:50; preferably, the protein or polypeptide drug is used in combination with the delivery synergist; preferably, the combination use comprises simultaneously using the protein or polypeptide drug and the delivery synergist in the form of a pharmaceutical composition; or separately using the protein or polypeptide drug and the delivery synergist in sequence; preferably, the combination use is to simultaneously use the protein or polypeptide drug and the delivery synergist in the form of a pharmaceutical composition.
  12. The pharmaceutical composition according to claim 11, further comprising a pharmaceutically acceptable carrier; preferably, the pharmaceutically acceptable carrier comprises a lubricant, a filler, a disintegrant, a flavoring agent, a colorant, a binder, an forming agent, a buffer, a diluent, a solubilizer, a tonicity regulator, a surfactant, a preservative, an isotonic agent, a stabilizer, and/or a chelating agent; preferably, the pharmaceutically acceptable carrier comprises a lubricant, a filler, and a disintegrant; preferably, the lubricant comprises magnesium stearate, glyceryl tribehenate, and/or stearic acid; preferably, the lubricant is selected from magnesium stearate; preferably, the filler is selected from mannitol and/or microcrystalline cellulose; preferably, the disintegrant is selected from croscarmellose sodium; preferably, the pharmaceutical composition further comprises one or more active pharmaceutical ingredients for use in combination with the protein or polypeptide drug; preferably, the active pharmaceutical ingredient is selected from an antidiabetic agent, an anti-obesity agent, an appetite-regulating agent, an antihypertensive agent, an agent for treating and/or preventing complications and conditions caused by or associated with diabetes, and an agent for treating and/or preventing complications and conditions caused by or associated with obesity; preferably, a dosage form of the pharmaceutical composition comprises a tablet, a capsule, an emulsion, an aqueous suspension, a dispersant, or a powder; preferably, the dosage form of the pharmaceutical composition is a tablet; preferably, the tablet is prepared by a dry granulation process and/or a direct mixing process; preferably, the tablet has a hardness of 30-90 N.
  13. Use of a substance shown below as a synergist for a drug delivery agent: hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, sucralfate, calcium bicarbonate, aluminum bicarbonate, magnesium bicarbonate, and/or magnesium hydroxide; wherein the delivery agent has a structure represented by formula (III): in formula (III), L represents linear or branched C5-C11 alkylene, and M represents Na + , K + , or NH 4 + ; preferably, L represents linear or branched C7-C9 alkylene, and M represents K + ; preferably, the delivery agent comprises a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; preferably, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid comprises a sodium salt, a potassium salt, and/or an ammonium salt; preferably, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is selected from a potassium salt, which has a structure represented by formula (II): or the delivery agent has a structure represented by formula (IV): CH 3 -(CH 2 )n-COOM, (IV) in formula (IV), n represents an integer from 4 to 10, and M represents Na + , K + , or NH 4 + ; preferably, n represents an integer from 6 to 8, and M represents Na + ; preferably, the delivery agent comprises a salt of caprylic acid, capric acid, and/or lauric acid; preferably, the delivery agent comprises a sodium salt, a potassium salt, and/or an ammonium salt of caprylic acid, capric acid, and/or lauric acid; or the delivery agent comprises a salt of chenodeoxycholic acid; preferably, the delivery agent comprises a sodium salt, a potassium salt, and/or an ammonium salt of chenodeoxycholic acid.
  14. A pharmaceutical composition, comprising a delivery agent and a delivery synergist, wherein the delivery agent has a structure represented by formula (III): in formula (III), L represents linear or branched C5-C11 alkylene, and M represents Na + , K + , or NH 4 + ; preferably, L represents linear or branched C7-C9 alkylene, and M represents K + ; preferably, the delivery agent comprises a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; preferably, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid comprises a sodium salt, a potassium salt, and/or an ammonium salt; preferably, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is selected from a potassium salt, which has a structure represented by formula (II): or the delivery agent has a structure represented by formula (IV): CH 3 -(CH 2 )n-COOM, (IV) in formula (IV), n represents an integer from 4 to 10, and M represents Na + , K + , or NH 4 + ; preferably, n represents an integer from 6 to 8, and M represents Na + ; preferably, the delivery agent comprises a salt of caprylic acid, capric acid, and/or lauric acid; preferably, the delivery agent comprises a sodium salt, a potassium salt, and/or an ammonium salt of caprylic acid, capric acid, and/or lauric acid; or the delivery agent comprises a salt of chenodeoxycholic acid; preferably, the delivery agent comprises a sodium salt, a potassium salt, and/or an ammonium salt of chenodeoxycholic acid; the delivery synergist comprises hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, sucralfate, calcium bicarbonate, aluminum bicarbonate, magnesium bicarbonate, and/or magnesium hydroxide; preferably, the delivery synergist comprises hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, and/or sucralfate; preferably, the delivery agent and the delivery synergist are in a mass ratio of 1:0.3-1:3; preferably, the delivery agent and the delivery synergist are in a mass ratio of 1:0.3-1:2.
  15. The pharmaceutical composition according to claim 14, further comprising a protein or polypeptide drug, wherein the protein or polypeptide drug comprises a hormone, a growth factor, a cytokine, an analgesic peptide, an enzyme, a coagulation factor, a peptide neurotransmitter, and/or an antibody; or the protein or polypeptide drug comprises a receptor agonist or antagonist; preferably, the receptor agonist or antagonist comprises a GLP-1 receptor agonist, a GLP-1 receptor antagonist, a GIP receptor agonist, a GIP receptor antagonist, and/or an insulin receptor agonist; preferably, the receptor agonist or antagonist comprises a GLP-1 receptor agonist; preferably, the GLP-1 receptor agonist comprises an exendin, GLP-1 or an analog, fragment, derivative, fusion protein, or conjugate thereof, or a pharmaceutically acceptable salt of the molecule described above; preferably, the GLP-1 receptor agonist has a structure represented by formula (I): preferably, the protein or polypeptide drug and the delivery agent are in a mass ratio of 1:5-1:150; preferably, the protein or polypeptide drug and the delivery agent are in a mass ratio of 1:10-1:50; preferably, the protein or polypeptide drug is used in combination with the delivery synergist; preferably, the combination use comprises simultaneously using the protein or polypeptide drug and the delivery synergist in the form of a pharmaceutical composition; or separately using the protein or polypeptide drug and the delivery synergist in sequence; preferably, the combination use is to simultaneously use the protein or polypeptide drug and the delivery synergist in the form of a pharmaceutical composition; preferably, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier; preferably, the pharmaceutically acceptable carrier comprises a lubricant, a filler, a disintegrant, a flavoring agent, a colorant, a binder, an forming agent, a buffer, a diluent, a solubilizer, a tonicity regulator, a surfactant, a preservative, an isotonic agent, a stabilizer, and/or a chelating agent; preferably, the pharmaceutically acceptable carrier comprises a lubricant, a filler, and a disintegrant; preferably, the lubricant comprises magnesium stearate, glyceryl tribehenate, and/or stearic acid; preferably, the lubricant is selected from magnesium stearate; preferably, the filler is selected from mannitol and/or microcrystalline cellulose; preferably, the disintegrant is selected from croscarmellose sodium; preferably, the pharmaceutical composition further comprises one or more active pharmaceutical ingredients for use in combination with the protein or polypeptide drug; preferably, the active pharmaceutical ingredient is selected from an antidiabetic agent, an anti-obesity agent, an appetite-regulating agent, an antihypertensive agent, an agent for treating and/or preventing complications and conditions caused by or associated with diabetes, and an agent for treating and/or preventing complications and conditions caused by or associated with obesity; preferably, a dosage form of the pharmaceutical composition comprises a tablet, a capsule, an emulsion, an aqueous suspension, a dispersant, or a powder; preferably, the dosage form of the pharmaceutical composition is a tablet; preferably, the tablet is prepared by a dry granulation process and/or a direct mixing process; preferably, the tablet has a hardness of 30-90 N.
  16. Use of the pharmaceutical composition according to any one of claims 11, 12, 14, and 15 in the manufacture of a medicament for preventing and/or treating a metabolism-related disease, a nerve-related disease, or a brain-related disease, wherein preferably, the metabolism-related disease comprises a carbohydrate metabolism disorder and/or a lipid metabolism disorder; preferably, the carbohydrate metabolism disorder comprises a disease related to abnormal blood glucose; preferably, the disease related to abnormal blood glucose comprises diabetes, diabetic oculopathy, diabetic heart disease, diabetic nephropathy, diabetic neuropathy, necrosis of distal lower limbs, atherosclerosis, coronary heart disease, myocardial infarction, cerebral thrombosis, cerebral hemorrhage, cerebral embolism, osteoporosis, hyperlipidemia, hypertension, obesity, fatty liver, and/or cirrhosis; preferably, the diabetes comprises hyperglycemia, type II diabetes, impaired glucose tolerance, type I diabetes, non-insulin-dependent diabetes, maturity-onset diabetes of the young (MODY), and/or gestational diabetes; preferably, the lipid metabolism disorder comprises a disease related to abnormal body weight; preferably, the disease related to abnormal body weight comprises anemia, gastroptosis, inflammatory bowel disease, dyspepsia, gastrointestinal ulcer, endocrine dyscrasia, osteoporosis, obesity, hypertension, hyperlipidemia, coronary heart disease, diabetes, fatty liver, joint deformity, pain, cancer, respiratory insufficiency, kidney diseases, hyperlipidemia, atherosclerosis, cirrhosis, angina pectoris, and/or myocardial infarction; preferably, the nerve-related disease comprises a neurodegenerative disease; preferably, the neurodegenerative disease comprises brain atrophy, cerebral ischemia, brain injury, epilepsy, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, spinocerebellar ataxia, Pick's disease, bovine spongiform encephalopathy, and/or Creutzfeldt-Jakob disease.
  17. A kit comprising the pharmaceutical composition according to any one of claims 11, 12, 14, and 15.

Description

TECHNICAL FIELD The present application relates to the field of biomedicine, and particularly to a composition providing improved oral bioavailability of a drug and a method therefor. BACKGROUND Oral administration has been the first choice of mainstream therapeutic drugs due to its simple operation, safety, effectiveness, variety of developable formulation forms, and the like. It is also favored by patients and has good patient compliance. However, many drugs with high demand are still administered by other routes, such as injection, due to various factors. For example, most polypeptide drugs such as insulin and GLP-1 agonists are currently administered by injection, which has the defect of low patient adaptability, making the administration to patients more difficult and causing long-term pain. Oral modification of drugs that are difficult to administer orally has been one of the important directions in drug research. At present, the mainstream oral administration regimen for drugs that are difficult to administer orally (such as protein and polypeptide drugs) is to prepare oral formulations with active drugs through oral delivery agents, such as sodium caprylate (C8Na), sodium caprate (C10Na), sodium laurate (C12Na), and sodium chenodeoxycholate. A relatively successful example of oral drug development is the GLP-1R agonist drug, semaglutide tablet (Rybelsus®), developed by Novo Nordisk, which increases the oral absorption availability of polypeptides by a regimen of adding a delivery agent, sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), to the GLP-1R agonist tablet. This drug has been approved for marketing in the United States, Europe, and other regions. However, the greatest difficulty in the current technology of oral protein or polypeptide drugs is still the delivery efficiency of drugs, and lower delivery efficiency leads to higher raw material costs. This is mainly because the presence of the gastrointestinal barrier makes it difficult for oral protein and polypeptide drugs to be delivered to the circulatory system in vivo. Therefore, there is an urgent problem to be solved in the art to improve the oral bioavailability of drugs that are difficult to administer orally (such as protein and polypeptide drugs), thereby saving the production cost of the drugs and benefiting more patients. CONTENT OF THE PRESENT INVENTION In order to achieve the object described above, the present application adopts the following technical solutions. In a first aspect, the present application provides use of a delivery synergist in improving the oral bioavailability of a protein or polypeptide drug, wherein the protein or polypeptide drug is used in combination with the delivery synergist, and the delivery synergist includes hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, sucralfate, calcium bicarbonate, aluminum bicarbonate, magnesium bicarbonate, and/or magnesium hydroxide; the protein or polypeptide drug is delivered by a delivery agent. In some preferred technical solutions, the delivery synergist includes hydrotalcite, aluminum phosphate, calcium carbonate, aluminum hydroxide, and/or sucralfate. In the use provided in the first aspect of the present application, the protein or polypeptide drugs may be of any type commonly used in the art, including but not limited to, a hormone, a growth factor, a cytokine, an analgesic peptide, an enzyme, a coagulation factor, a peptide neurotransmitter, and/or an antibody. In the use provided in the first aspect of the present application, the protein or polypeptide drug may further include a receptor agonist or antagonist commonly used in the art. In some preferred technical solutions, the receptor agonist or antagonist includes a GLP-1 receptor agonist, a GLP-1 receptor antagonist, a GIP receptor agonist, a GIP receptor antagonist, and/or an insulin receptor agonist. Further, the receptor agonist or antagonist includes a GLP-1 receptor agonist. Still further, the GLP-1 receptor agonist includes an exendin, GLP-1 or an analog, fragment, derivative, fusion protein, or conjugate thereof, or a pharmaceutically acceptable salt of the molecule described above. In some of the most preferred technical solutions, the GLP-1 receptor agonist has a structure represented by formula (I): In the use provided in the first aspect of the present application, the delivery agent may have a structure represented by formula (III): in formula (III), L represents linear or branched C5-C11 alkylene, and M represents Na+, K+, or NH4+. Further, L represents linear or branched C7-C9 alkylene, and M represents K+. Still further, L represents linear C7-C9 alkylene, and M represents K+. In some preferred technical solutions, the delivery agent includes a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid. Further, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid includes a sodium salt, a potassium salt, and/or an ammonium salt. In some of the most preferred technical s