Composition for realizing oral absorption of polypeptide

Abstract

The present application relates to an oral polypeptide composition system stably absorbed in the gastrointestinal tract, and specifically discloses an oral polypeptide composition. The composition comprises a polypeptide molecule (A), a surfactant (B), an amino acid monomolecular or a bimolecular combination (C). The molecular weight of a peptide drug used as a drug in the oral polypeptide composition is within a range of 0.1 kDa to 20 kDa. The action part of the composition system is small intestine or large intestine; and the polypeptide composition has obviously improved and increased stability and absorbability in the gastrointestinal tract.

Description

A composition for achieving oral absorption of polypeptides Technical Field The present invention belongs to the field of biomedicine and specifically relates to an oral polypeptide composition. Background Art Polypeptides are a class of compounds formed by the connection of multiple amino acids through peptide bonds, usually composed of 10-100 amino acid molecules, and are ubiquitously present in organisms. So far, tens of thousands of polypeptides have been discovered in organisms. They widely participate in and regulate the functional activities of various systems, organs, tissues, and cells in the body and play an important role in life activities. Polypeptide-based clinical therapeutic drugs exhibit the advantages of high efficiency, selectivity, and low toxicity and have been widely used in many diseases including diabetes, cancer, and metabolic diseases, making them more attractive than small molecule drugs (Fosgerau K, Hoffmann T. Peptide therapeutics: current status and future directions. Drug Discov Today. 2015; 20(1): 122–128.). Compared with small molecule drugs, polypeptide drugs have the characteristics of high efficiency, low toxicity, and strong specificity. The US FDA has approved more than 80 polypeptide drugs for marketing. Polypeptides are macromolecules with good hydrophilicity and extremely poor permeability. In addition, the gastrointestinal tract is rich in proteases that degrade polypeptides. Therefore, most of the marketed polypeptide drugs are injectables. Polypeptides are also easily degraded by peptidases in plasma, liver, and kidney, have a short half-life, and have poor compliance with injection administration, which poses challenges to patients' drug compliance. Especially in the case of long-term medication for chronic disease patients, it will cause problems such as long-term pain and injection aversion (Zizzari AT, et al. New perspectives in oral peptide delivery. Drug Discov Today. 2021; 26(4): 1097–1105.). In view of the above pain points of polypeptide drugs in clinical practice, changing the administration route and developing oral polypeptide drugs have become a promising solution. In addition, from the production level, compared with the production of injectable drugs, oral polypeptide drugs have a larger production scale and lower production costs. The function of the gastrointestinal tract is to digest carbohydrates, proteins and other nutrients into amino acids and monosaccharides, while protecting the body from pathogen invasion. The gastrointestinal tract is also the main obstacle to the oral administration of polypeptide drugs. Under fasting conditions, the gastric juice pH value is 1-2. The strong acidic environment can induce hydrolysis, deamination, oxidation and other reactions of polypeptides, resulting in inactivation. In addition, enzymes that can cleave polypeptides are distributed throughout the gastrointestinal tract, including pepsin secreted by gastric glands, trypsin, chymotrypsin, carboxypeptidase and elastase secreted by the pancreas, and aminopeptidase, endopeptidase and β-glutaminyl transpeptidase secreted by intestinal cells. Guo et al. used bacitracin and leupeptin as protease inhibitors to improve the oral absorption of angiotensin 1 converting enzyme inhibitory peptides. An ideal oral delivery system for polypeptide drugs should be able to keep the polypeptide molecules intact before reaching the absorption site, release the drug at the target absorption site, and there should preferably be some interaction between the delivery system and the release site. In addition, the system should be able to stay at the polypeptide release site to provide sufficient time and concentration gradient for the transmembrane transport of polypeptide drugs. Based on the research progress of comprehensive polypeptide drugs, there are currently two main technical challenges in oral administration of polypeptide drugs. One is the stability issue of polypeptide drugs in the gastrointestinal tract. Due to the presence of proteases in the gastrointestinal tract, polypeptide drugs are usually quickly decomposed into amino acids by proteases after oral administration, thus losing their drug activity (Wang J, et al. Toward oral delivery of biophar-maceuticals: an assessment of the gastrointestinal stability of 17 peptide drugs. Mol Pharm. 2015;12(3):966–973.). Generally, proteases are ubiquitous in the gastrointestinal tract, and the types and concentrations vary in different parts. In the positions closer to the front end, such as the stomach and duodenum, the concentration and activity of proteases are higher. Therefore, polypeptide drugs are quickly decomposed and inactivated after oral administration. In addition, the second challenge in oral administration of polypeptide drugs is the problem of gastrointestinal absorption efficiency. Generally speaking, the drug completes the gastrointestinal absorption process by penetrating layer by layer from the gastrointestinal tract into the local venous blood vessels through oral administration, enters the systemic circulation, and exerts its therapeutic effect. However, due to the structural characteristics of polypeptide drugs such as large molecular weight, it is difficult to penetrate physiological structures such as the mucus layer and epithelial cells of the gastrointestinal tract. Therefore, the gastrointestinal absorption rate of polypeptide drugs is extremely low (Verma S, Go and UK, Husain A, et al. Challenges of peptide and protein drug delivery by oral route: current strategies to improve the bioavailability. Drug Dev Res. 2021;82(7):927–944.). Commonly used oral delivery technologies for polypeptide drugs include: (1) Structural modification and cyclization of polypeptides: Polypeptides are easily degraded by various enzymes in the body. However, by cyclization or covalently PEGylating, lipidating, or glycosylating polypeptides, the enzyme stability of polypeptides can be improved, including their stability in the whole body system, and the half-life can be extended. Cyclosporine A (CsA) is a cyclic lipophilic 11-peptide, and its capsule was approved by the US FDA for marketing in 1990, and its oral bioavailability is as high as 25% - 30%; The trans-isomer analog of CsA, voclosporin Approved for marketing in January 2021 for the treatment of lupus nephritis, with an oral bioavailability of approximately 8% (HEO YA. Voclosporin: first approval[J]. Drugs, 2021, 81(5): 605-610.). Desmopressin acetate is a 9-peptide with certain hydrophilicity, a natural arginine vasopressin analogue, obtained by deaminating the first amino acid and replacing L-arginine with D-arginine at the 8th position. Although its oral bioavailability is only 0.08% - 0.16%, its synthesis cost is low and its potency is high, so it can be taken orally (KOTTKE D, BURCKHARDT BB, KNAAB TC, et al. Development and evaluation of a composite dosage form containing desmopressin acetate for buccal administration[J]. Int J Pharm X, 2021.3: 100082.). The pegylated insulin analogue Tregopil insulin (IN-105) developed by Indian Biocon has completed phase III clinical trials, and the ghrelin receptor agonist TZP-102 developed by US Ocera Therapeutics

[0018] and SCY635 developed by US Scynexis for the treatment of hepatitis C infection have all completed phase II clinical trials. Although cyclization can improve stability, the large polar surface formed by a large number of amide bonds also limits the oral absorption of cyclic peptides. Nielsen et al. detected the physicochemical parameters and oral absorption of 125 cyclic peptides, and most of them had poor bioavailability. How to improve the oral bioavailability of cyclic peptides remains to be studied in depth. Osmotic enhancement technology: Intestinal permeation enhancers (PEs) can transiently increase epithelial cell permeability and are one of the most widely used delivery strategies for improving the oral absorption of polypeptides in clinical practice. is the first marketed oral glucagon-like peptide-1 (GLP-1) analogue, developed by applying Emisphere Technologies The technology enables oral absorption. This technology utilizes a series of penetration enhancers based on medium-chain fatty acids, including sodium N-2-hydroxybenzoyl-caprylate (SNAC), sodium 8-[N-(2-hydroxy-5-chlorobenzoyl)amino]octanoate (5-CNAC), and N-(4-salicyl chloride)-4-aminobutyrate (4-CNAB), etc. Among them, SNAC is the most widely used and has been approved by the US FDA as a food additive. However, in order to solve the stability problem, this technology selects the stomach as the absorption site, thus sacrificing the absorption efficiency of the drug. Buckley et al. determined that oral semaglutide is absorbed in the stomach through intragastric imaging, the effect of food on absorption, pylorus ligation, and the distribution of semaglutide in the splenic vein and portal vein within 30 minutes after administration. SNAC (pKa1 = 4.5, pKa2 = 8.6) has a strong buffering effect in the stomach, can improve the enzymatic stability of semaglutide by adjusting the pH, and can also promote the penetration of semaglutide by promoting the depolymerization of semaglutide into monomers and interacting with the lipid membrane. Since the stomach is not the main absorption organ compared to the intestine, and the effect of the SNAC promoter in the stomach is limited, the overall technology has the problem of low drug absorption rate. In the previous preclinical research stage of beagle dogs and cynomolgus monkeys, the relative bioavailability of the oral preparation of this technology was in the range of 0.04 - 4.04%. In subsequent human experimental studies, only a bioavailability of 0.4 - 1% was shown. Oral octreotide is an oral delivery achieved through the TPE TM technology developed by Chiasma, and it is the only oral somatostatin analogue used to treat acromegaly. TPE TM technology forms a suspension by adding a polypeptide, a medium-chain fatty acid salt, and polyvinylpyrrolidone (PVP) plus a hydrophobic medium, and is delivered using an enteric capsule. Since this technology does not solve the technical challenge of stability, its scope of use is limited and it only works for polypeptide drugs with very good stability, and it is not a general-purpose delivery technology. In addition, since this technology only achieves an instantaneous osmotic promotion effect, the overall absorption rate is not high. According to the results of human experiments, the absolute bioavailability is only 0.7% (Tuvia S, Atsmon J, Teichman SL, et al. Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression. J Clin Endocrinol Metab. 2012;97(7):2362–2369.). The sodium caprylate used can transiently and reversibly open the tight junctions of the paracellular pathway. The results of its Phase III clinical study showed good efficacy and safety, and the blood drug level was comparable to that of octreotide injection. Although the promoting effect of PEs on the oral absorption of polypeptides has been fully confirmed, the spatio-temporal effect between polypeptides and PEs is often overlooked. After oral administration of semaglutide, high concentrations of semaglutide and SNAC can only be observed directly below or in the surface area of the tablet, and the absorption of semaglutide also occurs only in the local area where the tablet is located. The formulation with a faster release of SNAC than semaglutide disclosed in the patent WO2013189988A1 by Novo Nordisk has a higher bioavailability, probably because SNAC first dissolves to form a buffered environment and enhances cell membrane permeability, reducing unnecessary loss of semaglutide. Therefore, the impact of gastrointestinal motility on the co-delivery of polypeptides and PEs will also affect the oral absorption of polypeptides. The movement of the fasting stomach exhibits the characteristics of periodic migrating motor complexes, and the peristaltic ability of the duodenum and proximal jejunum is significantly higher than that of the ileum. Sladek et al. encapsulated PEs using insulin-related anionic polyelectrolyte nanoparticle complexes and achieved co-delivery using enteric coating technology. In addition, for PEs of the paracellular pathway, it may be necessary to appropriately increase the diffusion range of the formulation to open more tight junctions. In addition to the commercially available technologies, the one developed by Merrion Company The technology uses sodium caprylate as a permeation enhancer (PE) and has shown good blood glucose control ability and low risk of hypoglycemia in a Phase II clinical study on the delivery of long-acting oral basal insulin "I338". Oramed's POD technology: Oramed Pharma in Israel developed the Peptide Oral Delivery (POD) technology using EDTA as a permeation enhancer. The oral insulin developed using this technology failed in Phase III clinical trials. This technology selects the intestinal site for absorption, overcomes the stability problem by adding protease inhibitor excipients (BBI or KTI), and overcomes the problem of low absorption by using EDTA as a permeation enhancer. According to preclinical studies, this technology achieved a relative bioavailability of 5.41 ± 2.26% in beagle dog experiments (Li W-dw Y-Z, Zeng R, Greenberg-Shushlav Y, et al. Pharmacokinetic and pharmacodynamic profiles of orally, duodenally and subcuta-neously delivered insulin in beagle canines. Paper presented at: American Diabetes Association (ADA); June 10-14, 2016; New Orleans, LA. 2016.). However, due to the addition of protease inhibitors, this technology has safety risks during the use ratio and long-term drug administration for chronic diseases, which also partially explains the failure of the oral insulin developed based on this technology in Phase III clinical trials. Enteris Biopharma's Peptelligence technology: This technology selects the intestine as the absorption site and overcomes the stability problem by adding a large dose of organic acids (such as citric acid) to inhibit the protease activity in the local intestinal environment. In addition, this technology promotes the intestinal permeation and absorption of polypeptides by adding a surfactant, L-lauroyl carnitine, to solve the absorption problem. The orally administered leuprolide developed based on this technology showed an absolute bioavailability of 1.1 ± 0.18% in preclinical beagle dog studies and has now completed Phase II clinical trials. However, the large amount of acid used in this technology to inhibit intestinal proteases (a dosage of not less than 50 mg) has safety risks during long-term use. In addition, the overall absorption effect of this technology has not achieved a high bioavailability. (3) Nanotechnology: Nanoparticles (NPs) are solid particles with a particle size of 1 - 100 nm. They can not only protect polypeptides from degradation by enzymes in the gastrointestinal tract, but also increase the transmembrane absorption of the intestinal epithelium, and can achieve targeted therapeutic effects through ligand modification. Oshadi Icp is an NPs delivery system for compositions used to deliver insulin, proinsulin, and C -peptide insulin developed by Oshadi Company. This system uses pharmacologically inert hydrophobic silica nanoparticles as carriers and can form tight non-covalent bonds with polypeptides and polysaccharides. These nanoparticles can protect polypeptides from the effects of gastrointestinal and brush border peptidases and promote polypeptide absorption. The results of the published Phase II clinical study showed that Oshadi Icp has good safety, tolerance, and hypoglycemic effects in patients with type 1 diabetes. The hepatic-directed vesicle insulin (HDV-I) developed by Diasome Company can directly deliver insulin to the liver after surface modification, with a particle size < 150 nm. After oral administration, HDV-I is taken up in the intestine and passes through the hepatic portal vein, enabling normal insulin physiological responses. The results of the completed Phase II clinical study showed that HDV-I has significant hypoglycemic effects in both the oral glucose tolerance test and diabetic meals. Phase III clinical studies are in preparation. With the continuous progress of the physical and chemical characterization techniques and imaging techniques of nanostructures, the biocompatibility, reproducibility, and scalable production of NPs are still the difficulties in current research and await the update of core technologies. (4) Drug-device combination: The drug-device combination is a new direction for oral delivery of polypeptides, applicable to the delivery of a variety of different peptides, with lower requirements for polypeptide molecular size, stability, hydrophobicity, etc. The drug-device combination includes microneedles, intestinal patches, microcontainers, etc. Microneedles are the most promising technology among them. There are no pain receptors in the intestine, enabling painless drug delivery. The drug-device combination can, on the one hand, protect polypeptides from degradation by enzymes in the gastrointestinal tract, and on the other hand, achieve the unidirectional co-delivery of polypeptides and PEs in terms of time and space. The self-orienting millimeter-scale applicator (SOMA) jointly developed by the Massachusetts Institute of Technology and Novo Nordisk is a drug delivery system designed based on the rolling of leopard tortoises, which can automatically reset and adhere to the gastric mucosa. The internal spring can insert the insulin needle into the gastric wall without piercing the outer layer of the gastric wall. The team carried out in vivo studies of SOMA in rats and pigs using insulin as a model drug, and its blood drug level was comparable to that of subcutaneous injection. The robotic pill (RaniPill) developed by Rani Therapeutics consists of compartments filled with citric acid and sodium bicarbonate. When it enters the intestine, the compartment barrier is eroded, and after mixing, CO 2Expansion propulsion dissolves glycosyl micro needles through the outer layer of the capsule to penetrate the epithelium. The Rani Pill can deliver more than 10 kinds of antibody, polypeptide and protein drugs. In large animal experiments, 3 mg of oral insulin is equivalent to 80 units of subcutaneous injection, and the bioavailability exceeds 50%. It showed good safety in the completed phase I clinical study of delivering placebo. The luminal unfolding microneedle injector (LUMI) is another oral microneedle developed by the SOMA development team. This system consists of an enteric capsule, a spring and three degradable unfolding arms. When pH≥5.5, the surface coating of the capsule dissolves, and the compressed spring pushes the LUMI out of the capsule and unfolds it, ensuring that the microneedles are always in contact with the intestinal wall. By optimizing the unfolding force, this system has no risk of perforation in the ex vivo intestines of humans and pigs, and the oral bioavailability of pigs is more than 10% relative to subcutaneous injection. LUMI can also deliver other macromolecular drugs with oral barriers, such as vaccines, monoclonal antibodies, hormones and RNA. In summary, the existing technologies have limitedly solved the difficult problems of oral administration of polypeptide drugs, and only a few oral polypeptide products have been successfully developed and marketed. However, there are still problems in terms of scope of application, safety, absorption effect, stability, etc., which need to be further solved and optimized. Acylcarnitine is a compound formed by the combination of fatty acid and carnitine when fatty acid is transported to the inner membrane of mitochondria in vivo, and is generated from acyl-CoA and carnitine by the action of carnitine palmitoyltransferase I existing in the outer membrane of mitochondria. It has been reported that acylcarnitine is used as an absorption enhancer, which can promote the absorption of drugs such as polypeptides at the cellular level (Anwer, W., Ratto Velasquez, A., & Tsoukanova, V. (2020). Acylcarnitines at the Membrane Surface: Insertion Parameters for a Mitochondrial Leaflet Model. Biophysical journal, 118(5), 1032–1043.). The technology developed by Enteris uses citric acid as a pH regulator and acylcarnitine as a penetration enhancer to deliver polypeptides enterically. Dozens of products have been developed using this technology, including Ovarest, Tobrate, TbriaTM, etc. In addition, the existing reported related technologies have proposed to use acylcarnitine as an absorption enhancer for the development of oral preparations of polypeptide molecules. However, as shown in the above description, there is still room for improvement and optimization in terms of stability, safety and absorption effect improvement of the existing technologies. Summary of the Invention In a first aspect, the present invention provides an oral polypeptide composition, which composition comprises a polypeptide molecule (A), a surfactant (B), and an amino acid monomer or dimer combination (C). Furthermore, the components of the oral polypeptide composition can interact with each other to form nanoparticles, and the diameter of the nanoparticles is 0 - 1000 nm. Furthermore, the oral polypeptide composition further comprises a pH regulator (D). Furthermore, the action site of the oral polypeptide composition is the small intestine and / or the large intestine, and the composition can be stably absorbed in the small intestine and / or the large intestine. Furthermore, the polypeptide molecule is a compound containing multiple amino acids or containing at least one peptide bond and its pharmaceutically acceptable salts, and the molecular weight of the polypeptide molecule is 0.1 kDa to 20 kDa, preferably 0.1 kDa to 15 kDa, 0.1 kDa to 10 kDa, 0.1 kDa to 9.0 kDa, 0.1 kDa to 5.0 kDa, 0.1 kDa to 2.0 kDa; 0.5 kDa to 20 kDa, 0.5 kDa to 15 kDa, 0.5 kDa to 10 kDa, 0.5 kDa to 9.0 kDa, 0.5 kDa to 5.0 kDa, 0.5 kDa to 2.0 kDa; 1.0 kDa to 20 kDa, 1.0 kDa to 15 kDa, 1.0 kDa to 10 kDa, 1.0 kDa to 9.0 kDa, 1.0 kDa to 5.0 kDa, 1.0 kDa to 2.0 kDa; 5.0 kDa to 20 kDa, 5.0 kDa to 15 kDa, 5.0 kDa to 10 kDa, 5.0 kDa to 9.0 kDa; 10.0 kDa to 20 kDa, 10.0 kDa to 15 kDa; More preferably 0.1 kDa, 0.5 kDa, 1 kDa, 1.5 kDa, 2 kDa, 2.5 kDa, 3 kDa, 3.5 kDa, 4 kDa, 4.5 kDa, 5 kDa, 5.5 kDa, 6 kDa, 6.5 kDa, 7 kDa, 7.5 kDa, 8 kDa, 8.5 kDa, 9 kDa, 9.5 kDa, 10 kDa, 15 kDa, 20 kDa. Furthermore, the polypeptide molecule includes a linear structure and a cyclic structure. Furthermore, the polypeptide molecule includes modified peptides, derived peptides, and peptidomimetics. Furthermore, the polypeptide molecule includes, but is not limited to, glucagon-like peptide-1 (GLP-1), GLP-1 analogs, GLP-1 agonists, semaglutide, liraglutide, exenatide, exenatide-4, lixisenatide, taspoglutide, langlenatide, GLP-1(7 - 37), GLP-1(7 - 36)NH2 , dual agonists of GLP-1 receptor and glucagon receptor, oxyntomodulin, GLP-2, GLP-2 agonists or analogs, goserelin, buserelin, peptide YY (PYY), PYY analogs, glatiramer, leuprolide, desmopressin, glycopeptide antibiotics, bortezomib, corticotropin, sermorelin, luteinizing hormone releasing hormone, calcitonin, pentagastrin, oxytocin, nesiritide, enfuvirtide, eptifibatide, cyclosporine, glucagon, viomycin, thyrotropin releasing hormone (TRH), leucine-enkephalin, methionine-enkephalin, substance P (CAS No. 33507-63-0), a parathyroid hormone (PTH) fragment, linaclotide, carfilzomib, icatibant, cilengitide and prostaglandin F2a receptor modulators and their pharmaceutically acceptable salts. In some embodiments, the GLP-1 analogs are selected from acylated GLP-1 analogs, diacylated GLP-1 analogs, and long-acting albumin-binding fatty acid-derivatized GLP-1 analogs. In some embodiments, the GLP-2 agonists or analogs include, but are not limited to, teduglutide and elsioglutide. In some embodiments, the somatostatin analogs include, but are not limited to, octreotide and lanreotide or pasireotide. In some embodiments, the goserelin includes, but is not limited to, goserelin acetate. In some embodiments, the glatiramer includes, but is not limited to, glatiramer acetate. In some embodiments, the leuprolide includes, but is not limited to, leuprolide acetate. In some embodiments, the desmopressin includes, but is not limited to, desmopressin acetate and desmopressin monoacetate trihydrate. In some embodiments, the glycopeptide antibiotics include, but are not limited to, glycosylated cyclic or polycyclic nonribosomal peptides. Furthermore, the glycosylated cyclic or polycyclic nonribosomal peptides include, but are not limited to, vancomycin, teicoplanin, telavancin, bleomycin, ramoplanin or decaplanin), bortezomib, corticotropin, sermorelin, luteinizing hormone releasing hormone. In some embodiments, the calcitonin includes, but is not limited to, salmon calcitonin. In some embodiments, the α parathyroid hormone (PTH) fragment includes, but is not limited to, teriparatide, PTH(1-31) and PTH(2-34). In some embodiments, the polypeptide molecule is a peptide molecule drug, and the prostaglandin F2a receptor modulator is selected from PDC31. Further, the surfactant may be an acyl carnitine compound and / or an alkyl glycoside compound with a carbon chain length between C 8 and C 12 , and their pharmaceutically acceptable salts or solvates; the structural formula of the acyl carnitine compound is shown in Formula I: In Formula I; R 1 may be an alkyl compound with a carbon chain length of C 6 to C 14 . Further, the surfactant includes but is not limited to myristoyl-L-carnitine, decanoyl-L-carnitine, lauroyl-L-carnitine, dodecyl-beta-D-maltoside, tetradecyl-β-D-maltoside, and b-dodecyl-D-glucopyranoside. Further, the amino acid single molecule is selected from any one or more of glycine, alanine, valine, leucine, proline, tryptophan, serine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, and citrulline. Further, the amino acid dimer is a combination formed by connecting any two amino acid single molecules selected from glycine, alanine, valine, leucine, proline, tryptophan, serine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine, and citrulline through a peptide bond. Further, the amino acid dimer may be selected from one or more of diglycine, dialanine, divaline, dileucine, diproline, dityptophan, diserine, dicysteine, diphenylalanine, diasparagine, diglutamine, dithreonine, diaspartic acid, diglutamic acid, dilysin, diarginine, and dicitrulline. Further, the D-component pH regulator includes but is not limited to tartaric acid, oxalic acid, malic acid, citric acid, vitamin C, acetic acid, succinic acid, oxalic acid, and succinic acid, as well as physically stable forms such as their hydrates. Further, the dosage range of the pH regulator in the composition is 1 - 150 mg, 5 - 145 mg, 10 - 140 mg, 15 - 130 mg, 20 - 120 mg, 25 - 110 mg, 20 - 100 mg, 30 - 90 mg, 40 - 80 mg. Further, the mass ratio of the polypeptide molecule (A), surfactant (B), and amino acid single or double molecule combination (C) in the composition is 0-5: 0.1-20: 0.5-20, preferably 2-5: 5-20: 3-20, and more preferably 1: 6: 10; 1: 20: 3; 1: 10: 20; 1: 15: 7.5; 1: 8: 4; 5: 20: 15 In one embodiment, the polypeptide composition is semaglutide, lauroyl-L-carnitine, and diglycine; the mass ratio of the composition is 1: 6: 10; In one embodiment, the composition is semaglutide, L-octanoyl carnitine, and arginine; the mass ratio of the composition is 1: 6: 10. In one embodiment, the composition is octreotide and L-octanoyl carnitine (10); the mass ratio of the composition is 1: 10. In one example, the composition is thymopentin, diglycine, and citric acid; the mass ratio of the composition is 1: 20: 3. In one example, the composition is thymopentin, lauroyl-L-carnitine, diglycine, and citric acid; the mass ratio of the composition is 1: 10: 20: 3. In one example, the composition is octreotide, L-octanoyl carnitine, and diglycine; the mass ratio of the composition is 1: 15: 7.5. In one example, the composition is linaclotide, L-octanoyl carnitine, and diglycine; the mass ratio of the composition is 1: 15: 7.5. In one example, the composition is semaglutide and lauroyl-L-carnitine; the mass ratio of the composition is 1: 0.1. In one example, the composition is semaglutide and lauroyl-L-carnitine; the mass ratio of the composition is 1: 0.2. In one example, the composition is semaglutide and lauroyl-L-carnitine; the mass ratio of the composition is 1: 0.3. In one example, the composition is semaglutide and lauroyl-L-carnitine; the mass ratio of the composition is 1: 0.4. In one example, the composition is semaglutide and lauroyl-L-carnitine; the mass ratio of the composition is 1: 0.6. In one example, the composition is semaglutide, lauroyl-L-carnitine, diglycine, and citric acid; the mass ratio of the composition is 1: 8: 4: 4. In one example, the composition is semaglutide, lauroyl-L-carnitine, arginine, and citric acid; the mass ratio of the composition is 1: 8: 4: 4. In one embodiment, the composition is semaglutide, lauroyl-L-carnitine, diglycine, arginine, and citric acid; the mass ratio of the composition is 1:8:4:4:4. In one embodiment, the composition is semaglutide, lauroyl-L-carnitine, and arginine; the mass ratio of the composition is 1:8:4. In one embodiment, the composition is semaglutide, lauroyl-L-carnitine, diglycine, and citric acid; the mass ratio of the composition is 5:20:15:20. In one embodiment, the composition is semaglutide, lauroyl-L-carnitine, diglycine, and citric acid; the ratio of the composition is 5:20:15:10. In one embodiment, the composition is semaglutide, L-octanoyl carnitine, diglycine, and citric acid; the mass ratio of the composition is 5:20:15:20. In a second aspect, the present invention provides a pharmaceutical preparation, which comprises a composition of a polypeptide molecule (A), a surfactant (B), and an amino acid single molecule or combination (C), and a pharmaceutically acceptable carrier. Further, the polypeptide molecule (A), the surfactant (B), and the amino acid single molecule or combination (C) are the same as those described in the first aspect of the present invention. Further, the oral preparation includes tablets, capsules, capsules within capsules, micro-patch systems within capsules, lozenges, pills, Ovules, solutions, emulsions, suspensions, syrups, elixirs, powders and granules for reconstitution, dispersible powders and granules, pharmaceutically acceptable gums, chewable tablets, effervescent tablets, and multi-particle dosage forms. Further, the pharmaceutically acceptable carrier may include fillers, glidants, excipients, granulation binders, lubricants, disintegrants, etc. Further, the fillers include but are not limited to starches, sugars, celluloses, and inorganic salts. Further, the excipients include but are not limited to non-reducing sugars, microcrystalline cellulose, sodium citrate, calcium carbonate, calcium hydrogen phosphate, and glycine, and the disintegrants such as starch (preferably corn, potato, or tapioca starch), sodium starch glycolate, croscarmellose sodium, and certain complex silicates. Further, the granulation binders include but are not limited to polyvinylpyrrolidone, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), sucrose, and gum arabic. Further, the lubricants include but are not limited to magnesium stearate, stearic acid, glyceryl behenate, and talc. Similar types of solid compositions can also be used as fillers in hard capsules. Furthermore, the pharmaceutically acceptable carrier further includes various sweeteners, flavoring agents, coloring agents or dyes, combinations with emulsifying and / or suspending agents and combinations with diluents such as water, ethanol, propylene glycol and glycerol, and combinations thereof. In a third aspect, there is provided an application of a composition in the preparation of a medicament for treating a disease; the composition comprises a polypeptide molecule (A), a surfactant (B) and a combination (C) of single or double amino acid molecules, and a pharmaceutically acceptable carrier. Furthermore, the diseases include, but are not limited to, endocrine diseases, including glucose metabolism disorders, diabetes, obesity, hormone deficiency and osteoporosis; neurodegenerative diseases, including Alzheimer's disease and other forms of dementia, Parkinson's disease, multiple sclerosis and Huntington's disease; cardiovascular diseases, including atherosclerosis, hyper-coagulable state and hypocoagulable state, coronary artery disease and cerebrovascular events; hypertension, metabolic disorders, including obesity and vitamin deficiency; kidney diseases, including renal failure; blood diseases, including anemia of different entities; immune and rheumatic disorders, including autoimmune diseases and immune function deficiencies; inflammatory diseases, infectious diseases, including viral, bacterial, fungal and parasitic infections; neoplastic diseases; and multi-factorial diseases, including chronic pain, depression, different fibrotic states and short stature. Beneficial effects The composition system of the present application significantly improves the stability of polypeptide drugs in intestinal fluid and colon fluid; meanwhile, in vivo, the composition system significantly promotes the absorption effect of polypeptide drugs. Description of the drawings Figure 1 Stability analysis of semaglutide and its combination system in the small intestine. Figure 2 Stability analysis of octreotide and its combination system in the small intestine. Figure 3 Stability analysis of thymopentin and its combination system in the small intestine. Figure 4 Stability analysis of octreotide and its combination system in colon fluid. Figure 5 Stability analysis of linaclotide and its combination system in colon fluid. Figure 6 TEM characterization of OLP-C102. Figure 7 TEM characterization of OLP-C103. Figure 8 TEM characterization of OLP-C104. Figure 9 TEM characterization of OLP-C105. Figure 10 Analysis of the intestinal absorption of the composition system in rats. The effect is based on the blood drug concentration of the polypeptide drug, and the higher the concentration, the better the effect. Figure 11 Analysis of the absorption effect of single / double amino acid components on semaglutide in the composition system. Figure 12 Analysis of the absorption-promoting effect of pH regulators on semaglutide in the composition system. Figure 13 In vivo absorption analysis in rats. Figure 14 In vivo absorption analysis in beagle dogs. Detailed implementation manners The following further describes the detailed implementation manners of the present invention. It should be noted here that the description of these implementation manners is used to help understand the present invention, but does not limit the present invention. In addition, the technical features involved in the following described implementation manners can be combined with each other as long as they do not conflict with each other. In this article, the molecular weights of "polypeptide molecule", "peptide", "protein", "protein drug", "peptide molecule compound" and "peptide molecule drug" are specified in daltons (Da), which is an alternative name for the unified atomic mass unit (u). The term "kDa" refers to 1000 Da. The terms "polypeptide molecule", "peptide", "peptide molecule compound", "peptide molecule drug", "polypeptide" and "protein" used herein can be used interchangeably to refer to polymers of amino acid residues, including amino acid chains of any length, including full-length proteins, wherein the amino acid residues are connected by covalent peptide bonds, and the molecular weight ranges from about 0.1 kDa to 20 kDa; it also includes 0.1 kDa, 0.5 kDa, 1 kDa, 1.5 kDa, 2 kDa, 2.5 kDa, 3 kDa, 3.5 kDa, 4 kDa, 4.5 kDa, 5 kDa, 5.5 kDa, 6 kDa, 6.5 kDa, 7 kDa, 7.5 kDa, 8 kDa, 8.5 kDa, 9 kDa, 9.5 kDa, 10 kDa, 15 kDa, 20 kDa. The term "peptidomimetic" as used herein refers to a small protein-like chain that is designed to mimic a peptide. The peptide molecule drug of the present invention can be any peptide suitable for use as a medicament; for example, the peptide drug can be a linear peptide drug or a cyclic peptide drug (for example, a cyclic peptide drug cyclized via at least one amide bond). It can also be a modified or derivatized peptide drug, such as a polyethylene glycolated peptide drug or a fatty acid acylated peptide drug or a fatty diacid acylated peptide drug, or it can be an unmodified peptide drug. In particular, at its N-terminus and / or at its C-terminus, it can be unmodified, that is, it can have a free N-terminus (-NH 2 ) and / or a free C-terminus (-COOH). Thus, the drug can have a free (unmodified) N-terminus, or it can have a free (unmodified) C-terminus, or it can have a free N-terminus and a free C-terminus. In addition, the peptide drug can have no histidine residues and / or no cysteine residues. In some embodiments, the polypeptide molecule includes proteins, such as, but not limited to, therapeutic agents, nutritional products, mucopolysaccharides, lipids, carbohydrates, steroids, hormones, growth hormone (GH), growth hormone-releasing hormone (GHRH), epidermal growth factor, vascular endothelial growth and permeability factor (VEGPF), nerve growth factor, cytokines, interleukins, interferons, GMCSF, hormone products, nerve factors, neurotrophic factors, neurotransmitters, neuromodulators, enzymes, antibodies, peptides, protein fragments, vaccines, adjuvants, antigens, immune stimulatory or inhibitory factors, hematopoietic factors, anti-cancer products, anti-inflammatory drugs, anti-parasitic compounds, anti-microbial drugs, nucleic acid fragments, plasmid DNA vectors, cell proliferation inhibitors or activators, cell differentiation factors, blood coagulation factors, immunoglobulins, anti-angiogenic products, negative selection markers or "suicide" drugs, toxic compounds, anti-angiogenic drugs, polypeptides, and anti-cancer drugs, nucleotides, etc., and their structurally similar equivalents. In some embodiments, the polypeptide molecule includes, but is not limited to: glucagon-like peptide-1 (GLP-1), GLP-1 analogs, GLP-1 agonists (also referred to as "glucagon-like peptide-1 receptor agonists" or "GLP-1 receptor agonists"), semaglutide, liraglutide, exenatide, exenatide-4, lixisenatide, taspoglutide, langlenatide, GLP-1(7-37), GLP-1(7-36)NH 2 , dual agonists of GLP-1 receptor and glucagon receptor, gastrin-releasing peptide, GLP-2, GLP-2 agonists or analogs, goserelin, buserelin, peptide YY (PYY), PYY analogs, glatiramer acetate, leuprolide, desmopressin, glycopeptide antibiotics, bortezomib, corticotropin, sermorelin, luteinizing hormone-releasing hormone, calcitonin, pentagastrin, oxytocin, nesiritide, enfuvirtide, eptifibatide, cyclosporine, glucagon, viomycin, thyrotropin-releasing hormone (TRH), leucine-enkephalin, methionine-enkephalin, substance P (CAS No. 33507-63-0), a parathyroid hormone (PTH) fragment, linaclotide, carfilzomib, icatibant, cilengitide, and prostaglandin F2a receptor modulators, and their pharmaceutically acceptable salts. In some embodiments, the GLP-1 analogs are selected from acylated GLP-1 analogs, diacylated GLP-1 analogs, and long-acting albumin-bound fatty acid-derivatized GLP-1 analogs. In some embodiments, the GLP-2 agonists or analogs include, but are not limited to, teduglutide and elsiglutide. In some embodiments, the somatostatin analogs include, but are not limited to, octreotide and lanreotide or pasireotide. In some embodiments, the goserelin includes, but is not limited to, goserelin acetate. In some embodiments, the glatiramer includes, but is not limited to, glatiramer acetate. In some embodiments, the leuprorelin includes, but is not limited to, leuprorelin acetate. In some embodiments, the desmopressin includes, but is not limited to, desmopressin acetate and desmopressin monoacetate trihydrate. In some embodiments, the glycopeptide antibiotics include, but are not limited to, glycosylated cyclic or polycyclic non-ribosomal peptides. Furthermore, the glycosylated cyclic or polycyclic non-ribosomal peptides include, but are not limited to, vancomycin, teicoplanin, telavancin, bleomycin, ramoplanin or decaplanin), bortezomib, corticotropin, sermorelin, luteinizing hormone-releasing hormone (LHRH; also referred to as "gonadotropin-releasing hormone"). In some embodiments, the calcitonin includes, but is not limited to, salmon calcitonin. In some embodiments, the α parathyroid hormone (PTH) fragment includes, but is not limited to, teriparatide (also referred to as "PTH(1-34)"), PTH(1-31) and PTH(2-34). In some embodiments, the prostaglandin F2a receptor modulator is selected from PDC31. As used herein, the term "non-natural amino acid" refers to an amino acid that is not one of the 20 common amino acids (i.e., alanine, cysteine, aspartic acid, glutamic acid, phenylalanine, lysine, histidine, isoleucine, lysine, leucine, methionine, asparagine, proline, glutamine, arginine, serine, threonine, valine, tryptophan, and tyrosine), or pyrrolysine or selenocysteine. Other terms that may be used synonymously with the term "non-natural amino acid" are "non-naturally encoded amino acid", "unnatural amino acid", and "non-naturally occurring amino acid". The term "non-natural amino acid" includes, but is not limited to, amino acids that are naturally occurring through the modification of naturally encoded amino acids (including, but not limited to, the 20 common amino acids or pyrrolysine and selenocysteine), but are not incorporated into the growing polypeptide chain by the translation complex itself. Examples of naturally occurring amino acids that are not naturally encoded include, but are not limited to, N-acetylglucosaminyl-L-serine, N-acetylglucosaminyl-L-threonine, and O-phosphotyrosine. In addition, the term "non-natural amino acid" includes, but is not limited to, amino acids that are not naturally occurring and can be obtained by synthesis or can be obtained by modifying non-natural amino acids. Non-natural amino acids may include amino acids having a D-isomer configuration. In addition to natural amino acids, the amino acids may be D-amino acids or non-natural amino acids, and the molecular structure may further contain other substituents or modifications. For example, if the peptide active ingredient is salmon calcitonin, the salmon calcitonin may be amidated at its C-terminus. Some peptides may be amidated at positions where they are not naturally amidated, or may be otherwise modified. As used herein, the salts in the term "pharmaceutically acceptable salts" refer to both water-soluble salts and water-insoluble salts, such as acetate, aminosulphonate (4,4-diaminostilbene-2,2'-disulphonate), benzenesulphonate, benzoate, bicarbonate, bisulphate, bitartrate, borate, bromide, butyrate, calcium edetate, dextro-camphorsulphonate, carbonate, chloride, citrate, clavulanate, dihydrochloride, edetate, ethanedisulphonate, lauryl propionate sulphate, ethanesulphonate, fumarate, glucoheptonate, gluconate, glutamate, glycouylarsanilate, hexafluorophosphate, hexylresorcinol, haemin, hydrobromide, hydrochloride, hydroxy-naphthoate, iodide, isothiocyanate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methyl bromide, methyhiitrate, methyl sulphate, galactarate, naphthalenesulphonate, nitrate, N-methylglucamine ammonium salt, 3-hydroxy-2-naphthoate, oleate, oxalate, palmitate, pamoate (1,1'-methylene-bis-2-hydroxy-3-naphthoate, embonate), pantothenate, phosphate / diphosphate, picrate, polygalacturonate, propionate, p-toluenesulphonate, salicylate, stearate, basic acetate, succinate, sulphate, sulphonate, suramate, tannate, tartrate, theoclate, toluenesulphonate, triethyl iodide and valerate. The compositions of the present invention may additionally comprise a pharmaceutically acceptable carrier, which is an aqueous or anhydrous agent, for example, alcohol-containing or oil-containing, or a mixture thereof, and may contain surfactants, emollients, lubricants, stabilizers, dyes, fragrances, preservatives, acids or bases for adjusting pH, solvents, emulsifiers, gelling agents, emollients, stabilizers, wetting agents, sustained release agents, humectants, or other ingredients commonly included in pharmaceutical compositions in special forms. Pharmaceutically acceptable carriers are known in the art and include, for example, aqueous solutions such as water or physiological buffer saline or other solvents or carriers such as ethylene glycol, glycerol, and oils such as olive oil or injectable organic esters. Pharmaceutically acceptable carriers may contain physiologically acceptable compounds, for example, the compounds function to, for example, stabilize or increase the absorption of specific inhibitors, for example, carbohydrates such as glucose, sucrose or dextran, antioxidants such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins or other stabilizers or excipients. Pharmaceutically acceptable carriers may also be selected from substances such as distilled water, benzyl alcohol, lactose, starch, talc, magnesium stearate, polyvinylpyrrolidone, alginic acid, silica gel, titanium dioxide, and flavoring agents. The composition formulations described herein are intended to provide a composition system that can be used in an oral dosage form, and the formulations can be in the form of, for example, tablets (e.g., coated or uncoated tablets), capsules (e.g., gelatin capsules or HPM capsules), capsules within capsules, micro-patch systems within capsules, lozenges, pills, Ovules, solutions, emulsions, suspensions, syrups, elixirs, powders and granules for reconstitution, dispersible powders and granules, pharmaceutically acceptable gums, chewable tablets, effervescent tablets, and multi-particulate dosage forms. The composition formulations described herein, such as pills, tablets, capsules, etc., may also contain binders such as tragacanth, gum arabic, corn starch, or gelatin; excipients such as dicalcium phosphate; disintegrants such as corn starch, potato starch, or alginic acid; lubricants such as magnesium stearate; and sweeteners such as sucrose, lactose, or saccharin. When the dosage unit form is a capsule, in addition to the types of materials described above, it may contain a liquid carrier such as a fatty oil. The diseases, disorders, or conditions related to the present invention include, but are not limited to, endocrine disorders, including carbohydrate metabolism disorders, diabetes, obesity, hormone deficiencies, and osteoporosis; neurodegenerative diseases, including Alzheimer's disease and other forms of dementia, Parkinson's disease, multiple sclerosis, and Huntington's disease; cardiovascular diseases, including atherosclerosis, hyper-coagulable state and hypocoagulable state, coronary artery disease, and cerebrovascular events; hypertension, metabolic disorders, including obesity and vitamin deficiencies; kidney diseases, including renal failure; blood diseases, including anemia of different entities; immune and rheumatic disorders, including autoimmune diseases and immunodeficiencies; inflammatory diseases, infectious diseases, including viral, bacterial, fungal, and parasitic infections; neoplastic diseases; and multi-factorial diseases, including chronic pain, depression, different fibrotic conditions, and short stature. As used herein, the terms "subject" or "patient" can be an animal (e.g., non-human animal), vertebrate, mammal, rodent (e.g., guinea pig, hamster, rat, mouse), murine (e.g., mouse), canine (e.g., dog), feline (e.g., cat), porcine (e.g., pig), equine (e.g., horse), primate, simian (e.g., monkey or ape), monkey (e.g., marmoset, baboon), ape (e.g., gorilla, chimpanzee, orangutan, gibbon) or human. In the context of the present invention, it is also contemplated to treat animals that are economically or agriculturally important. Non-limiting examples of agriculturally important animals are sheep, cattle and pigs, while, for example, cats and dogs can be considered economically important animals. Preferably, the subject / patient is a mammal; more preferably, the subject / patient is a human or non-human mammal (such as, for example, guinea pig, hamster, rat, mouse, rabbit, dog, cat, horse, monkey, ape, marmoset, baboon, gorilla, chimpanzee, orangutan, gibbon, sheep, cattle or pig). Octreotide was first synthesized in 1979 and is an octapeptide that mimics the pharmacology of natural somatostatin, although it is a more potent inhibitor of growth hormone, glucagon and insulin than the natural hormone. Octreotide or other somatostatin analogs can be administered in accordance with one or more embodiments of the present invention for treating or preventing subjects suffering from the following diseases or disorders, such as acromegaly, gastrointestinal motility disorders, flushing episodes associated with carcinoid syndrome, portal hypertension, endocrine tumors (e.g., benign tumors, vasoactive intestinal peptide tumors), gastroparesis, diarrhea, pancreatic fistula or pancreatic pseudocyst. The experimental methods in the following examples are all conventional methods unless otherwise specified, and the test materials used in the following examples are all commercially available through conventional channels unless otherwise specified. Example 1 Stability Test 1.1 Small intestine stability experiment Method for preparing small intestine fluid: directly isolate the small intestine from the animal body, and squeeze and collect the small intestine contents. Small intestine stability: mix the composition system with small intestine fluid at a ratio of 1:10 and pipette. The reaction system is incubated in a constant temperature shaker at 37°C at a speed of 100 rpm, and samples are taken at 0, 0.17, 0.33, 0.5, 1, 1.5, 2 h. The mixed samples are centrifuged at 10,000 rpm at 4°C for 10 min. The supernatant is collected for quantitative analysis of polypeptide drugs. 1.1.1 Prepare the composition system using semaglutide solution at a concentration of 1 mg / ml. The content of semaglutide in all composition systems is the same, and the numbers in parentheses are the mass percentage of each component in the system. Table 1 List of composition systems prepared with semaglutide solution in the small intestine As can be seen from Figure 1, the composition systems OLP-A101 and OLP-A102 of the present application significantly improve the stability of semaglutide in intestinal fluid. 1.1.2 Prepare the composition system using octreotide solution at a concentration of 1 mg / ml. The content of octreotide in all composition systems is the same, and the numbers in parentheses represent the mass percentage of each component in the system. Table 2 List of composition systems prepared with octreotide solution in the small intestine The above chart results indicate that the composition system OLP-A201 significantly improves the stability of octreotide in intestinal fluid. 1.1.3 Prepare the composition system using thymopentin solution at a concentration of 1 mg / ml. The content of thymopentin in all composition systems is the same, and the numbers in parentheses represent the mass percentage of each component in the system. Table 3 List of composition systems prepared with thymopentin solution in the small intestine As shown by the results in Figure 3, the composition systems OLP-A301 and OLP-A302 significantly improve the stability of thymopentin in intestinal fluid. 1.2 Colonic (large intestine) stability experiment: 1. Method for preparing basal solution: Weigh peptone water and yeast extract and add them to a glass flask containing distilled water. Then, sequentially weigh 0.1 g of NaCl, 0.04 g of K 2 HPO 4 , 0.01 g of MgSO 4 .7H 2 O and 0.01 g of CaCl 2 .6H 2 O and add them to the glass flask, and dissolve them under stirring. After all the salts are dissolved, add 0.5 g of L-cysteine, 0.05 g of hemin chloride, 4 mL of 0.025% resazurin solution, and 2 g of NaHCO 3 . Add distilled water to make the final volume reach 1 L, and continue stirring for 20 - 30 minutes until the solution turns red to bright red for standby. 2. Method for preparing colonic fluid: Weigh 2 g of large intestine content into a 50 mL centrifuge tube, and add basal solution to make it 20 g. Mix well with a spatula to obtain a uniform 10% colonic fluid. 3. Colonic stability: Mix the composition system with 10% colon fluid at a ratio of 1:20, and pipette. Incubate and culture the reaction system in an anaerobic workstation (nitrogen: hydrogen: carbon dioxide = 8:1:1, ambient temperature 37 °C, humidity 75%). Absorb samples at 0, 0.5, 1, 2, 3, and 4 h. Centrifuge the mixed samples at 10000 rpm for 10 min at 4 °C. Collect the supernatant for quantitative analysis of the polypeptide drug. 1.2.1 Prepare the composition system using octreotide solution at a concentration of 1 mg / ml. The content of octreotide in all composition systems is the same. The numbers in parentheses represent the mass percentage of each component in the system. Table 4 List of composition systems prepared with octreotide solution in the colon Figure 4 shows that the composition system OLP-B101 significantly improves the stability of octreotide in human colon fluid. 1.2.2 Prepare the composition system using linaclotide solution at a concentration of 1 mg / ml. The content of linaclotide in all composition systems is the same. The numbers in parentheses represent the mass percentage of each component in the system. Table 5 List of composition systems prepared with linaclotide solution in the colon As shown in Figure 5, the composition system OLP-B201 significantly improves the stability of linaclotide in human colon fluid. Example 2 Characterization experiment of the composition system Perform particle size and diameter studies on the characterization of the composition system. Specifically, for the DLS (dynamic light scattering) particle size study, add the composition system to a cuvette and measure the particle diameter and polydispersity index (PDI) of the composition system using a Zetasizer Nano ZS (Malvern Instruments). Prepare the composition system using semaglutide solution at a concentration of 5 mg / ml and conduct particle size characterization and diameter studies. The numbers in parentheses represent the mass percentage of each component in the system. As shown in Table 6: Table 6 Particle size characterization of the composition system In addition, perform TEM (transmission electron microscopy) analysis on the above composition system. Specifically, for the TEM particle diameter study, lyophilize the composition system and reconstitute it with ultrapure water. Drop 20 μL of the reconstituted solution onto a copper grid; when the liquid is almost dry, add an appropriate amount of 2% phosphotungstic acid aqueous solution to the copper grid and incubate for 30 s; use absorbent paper to remove the excess liquid on the copper grid and air dry; observe the particle morphology of the composition system through a transmission electron microscope (TEM, JEM-2010, JEOL). The TEM results are shown in Figures 6 - 9. In summary, the DLS and TEM data indicate that the composition system of the present application forms nanoparticles with a particle size of 0-1000 nm. This characterization structure is specifically described in this patent and belongs to the protection scope of the composition system. Intestinal absorption experiment of the composition system in Example 3 for rats: This study was conducted using SD rats. An intestinal opening was made in the abdomen of the rats through an experimental operation, and a communicating vessel was used at the opening to maintain patency in the laboratory and closure in the non-experimental state. After the intestinal opening surgery of the rats, the rats were observed for 3 days. After recovering normal physiological activities, they were used as experimental rats for subsequent absorption experiments. Injection experiment: On the day of the experiment, the composition system was prepared. An intestinal injection was given at a drug dose of 2 mg / kg. After the injection, the intestinal opening was closed, and blood was taken from the orbital cavity of the rats at the following time points: 15 min, 30 min, 1 h, 2 h, 4 h. Blank blood was taken before drug administration as the 0-point blood sample standard for the experiment, and the blood collection volume at each blood collection point was 200 μl. Sample treatment: The whole blood of the rats was collected and centrifuged. After centrifugation, the supernatant serum blood sample was frozen at -20 °C and subsequently used for mass spectrometry detection and analysis. 3.1 The content of semaglutide in all the composition systems shown in the following table is the same. The numbers in parentheses are the mass percentage of each component in the system. Table 7 Composition systems for intestinal absorption in rats As shown in Figure 10, after drug administration, the absorption effects of the composition systems OLP-D101 and OLP-D102 are better than those of the blank control group (OLP-D100). The data show that the peak blood drug concentration of semaglutide in all groups reaches within 1 hour. In addition, since single / double amino acid components have a good promoting effect on the absorption of semaglutide, to further explore whether a synergistic effect can occur when using multiple single / double amino acid components, a new group of system OLP-D103 was added; compared with the OLP-D101 and OLP-D102 systems, there is no synergistic effect (as shown in Figure 11). In addition, a new composition system OLP-D104 was added to optimize the component ratio and adjust the dosage of CA, that is, CA was not used, and it was compared with OLP-D102 (containing CA). The results show (Figure 12) that when CA is not used, the intestinal absorption of semaglutide slightly decreases, but there is still a great advantage compared with the single semaglutide group; that is, CA in this system has an auxiliary effect rather than a key effect on promoting the absorption of semaglutide, and the use concentration of CA may show a "bell-shaped" or "linear" effect. Oral administration experiment of the composition system in Example 4 First, the composition system powder was prepared according to the following scheme. Specifically, each component was precisely weighed according to the mass configuration ratio shown in the following table, and after weighing, they were mixed evenly. Table 8 Oral Composition Systems 4.1 Rat Experiment The prepared composition system powders OLP-E100, OLP-E101, and OLP-E102 were surgically implanted into the rat intestine and the incision was sutured. Subsequently, blood was collected from the rat orbital cavity at the following time points: 30 min, 1 h, 2 h, 3 h, and 4 h. Blank blood was collected before administration as the 0-point blood sample for the experiment, and the blood collection volume at each blood collection point was 200 μl. Sample processing: The collected rat whole blood was centrifuged, and the supernatant serum blood sample was frozen at -20°C for subsequent mass spectrometry detection and analysis. The rat absorption experiment confirmed that the composition systems OLP-E101 and OLP-E102 showed a significant effect of promoting the absorption of polypeptide drugs (Figure 13, Table 9). Table 9 Absorption Effect in Rats 4.2 Beagle Dog Experiment The prepared composition system powders OLP-E100 and OLP-E103 were administered to beagle dogs by gavage. Subsequently, blood was collected from the cephalic vein of the beagle dogs at the following time points after administration: 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 h. Blank blood was collected before administration as the 0-point blood sample for the experiment, and the blood collection volume at each blood collection point was 1 ml. Sample processing: The collected beagle dog whole blood was centrifuged, and the supernatant serum blood sample was frozen at -20°C for subsequent mass spectrometry detection and analysis. The oral administration experiment on beagle dogs demonstrated that the composition system OLP-E103 showed a continuous and significant enhancement effect on the absorption of semaglutide (see Figure 14, Table 10). Table 10 Absorption Effect in Beagle Dogs

Claims

1. An oral polypeptide composition, comprising a polypeptide molecule (A), a surfactant (B), and an amino acid single molecule or double molecule combination (C).

2. The oral polypeptide composition according to claim 1, characterized in that: The components of the oral polypeptide composition can interact with each other to form nanoparticles, and the diameter of the nanoparticles is 0-1000nm.

3. The oral polypeptide composition according to claim 1, characterized in that: The oral polypeptide composition further comprises a pH adjuster (D).

4. The oral polypeptide composition according to claim 1, characterized in that: The oral polypeptide composition has an action site in the small intestine and / or large intestine, and the composition can be stably absorbed in the small intestine and / or large intestine.

5. The oral polypeptide composition according to claim 1, characterized in that: The polypeptide molecules include but are not limited to glucagon-like peptide-1 (GLP-1), GLP-1 analogs, GLP-1 agonists, semaglutide, liraglutide, exenatide, exenatide-4, lixisenatide, tasmoglutide, langlenatide, GLP-1 (7-37), GLP-1 (7-36) NH2, GLP-1 receptor, dual agonists of glucagon receptor, oxyntomodulin, GLP-2, GLP-2 agonists or analogs, goserelin, buserelin, peptide YY (PYY), PYY analogs, glatiramer, Leuprorelin, dezapressin, glycopeptide antibiotics, bortezomib, corticotropin, sermorelin, luteinizing hormone-releasing hormone, calcitonin, pentagastrin, oxytocin, nesiritide, enfuvirtide, eptifibatide, cyclosporine, glucagon, puromycin, thyrotropin-releasing hormone (TRH), leucine-enkephalin, methionine-enkephalin, substance P (CAS No. 33507-63-0), alpha parathyroid hormone (PTH) fragment, linaclotide, carfilzomib, icatibant, cilengitide and prostaglandin F2a receptor modulators and pharmaceutically acceptable salts thereof.

6. The oral polypeptide composition according to claim 1, characterized in that: The surfactant may be an acylcarnitine compound and / or a carbon chain length of C8 to C 12 The alkyl glycoside compounds and pharmaceutically acceptable salts or solvates thereof; the structural formula of the acylcarnitine compounds is shown in Formula I: R 1 The carbon chain length can be C6 to C 14 of alkyl compounds.

7. The oral polypeptide composition according to claim 1, characterized in that: The amino acid single molecule is selected from any one or more of glycine, alanine, valine, leucine, proline, tryptophan, serine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine and citrulline.

8. The oral polypeptide composition according to claim 1, characterized in that: The amino acid bimolecule is selected from a combination of any two amino acid monomolecules of glycine, alanine, valine, leucine, proline, tryptophan, serine, cysteine, phenylalanine, asparagine, glutamine, threonine, aspartic acid, glutamic acid, lysine, arginine and citrulline connected by peptide bonds.

9. A pharmaceutical preparation comprising a polypeptide molecule (A), a surfactant (B) and a composition of a single molecule or a combination of amino acids (C), and a pharmaceutically acceptable carrier.

10. Use of a composition in the preparation of a drug for treating a disease; the composition comprises a polypeptide molecule (A), a surfactant (B) and a combination of amino acid monomolecules or bimolecules (C), and a pharmaceutically acceptable carrier.

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