CN113230386B - Thymalfasin composition and application thereof - Google Patents
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Abstract
Thymalfasin compositions and uses thereof. In order to solve the problem that thymosin in the prior art cannot be orally taken, the invention provides a polypeptide composition which comprises a polypeptide, a soybean trypsin inhibitor and a first absorption enhancer in a therapeutically effective amount, wherein the first absorption enhancer is a surfactant. It can realize oral administration of thymosin. On the other hand, the application of the thymosin in preparing the medicine for preventing or treating hepatitis B and enhancing immune response is provided.
Description
The priority of the chinese patent application entitled "thymalfasin composition and use thereof" filed at 202110248309.2 by the chinese patent office on 7.07/03 of 2021, which is hereby incorporated by reference in its entirety.
Technical Field
The invention belongs to the field of oral delivery of polypeptides, and particularly relates to oral delivery of thymosin.
Background
The thymosin is a group of polypeptides secreted by thymus gland and having physiological activity, and is a small molecular polypeptide with nonspecific immune effect extracted from thymus tissue of animals such as healthy calf.
The currently clinically used thymosin medicaments comprise thymosin, thymopentin and thymalfasin, and are all related to polypeptide hormones secreted by thymus. Thymalfasin is a thymosin alpha 1 separated and purified from animal thymus, consists of 28 amino acids and has immunocompetence. The medicine is mainly used for treating immunodeficiency and virus infection clinically, and is a first-line medicine for treating hepatitis B. Thymalfasin treatment of chronic hepatitis b is mainly achieved by enhancing T cell function, which exerts an immunomodulatory effect by increasing the number of lymphocytes, CD3 and CD4 cells, etc. However, thymosin cannot be taken orally.
Disclosure of Invention
1. Problems to be solved
In order to solve the problem that thymosin in the prior art cannot be orally taken, the invention provides a polypeptide composition which comprises a polypeptide, a soybean trypsin inhibitor and a first absorption enhancer in a therapeutically effective amount, wherein the first absorption enhancer is a surfactant. It can realize oral administration of thymosin. On the other hand, the application of the thymosin in preparing the medicine for preventing or treating hepatitis B and enhancing immune response is provided.
2. Technical scheme
In order to solve the above problems, the present invention adopts the following technical solutions.
A polypeptide composition comprising a therapeutically effective amount of a polypeptide, a soybean trypsin inhibitor, and a first absorption enhancer, the first absorption enhancer being a surfactant.
In some embodiments of the invention, the polypeptide is a thymosin peptide.
In some embodiments of the invention, the polypeptide is thymalfasin.
In one embodiment, the polypeptide is 0.5mg to 100mg per dosage unit. In one embodiment, the polypeptide is 1mg to 100mg per dosage unit. In one embodiment, the polypeptide is 1mg to 60mg per dosage unit. In one embodiment, the polypeptide is 1mg to 50mg per dosage unit. In one embodiment, the polypeptide is 1mg to 45mg per dosage unit. In one embodiment, the polypeptide is 1mg to 40mg per dosage unit. In one embodiment, the polypeptide is 1mg to 35mg per dosage unit. In one embodiment, the polypeptide is 1mg to 30mg per dosage unit. In one embodiment, the polypeptide is 5mg to 30mg per dosage unit. In one embodiment, the polypeptide is 5mg to 25mg per dosage unit. In one embodiment, the polypeptide is 5mg to 20mg per dosage unit. In one embodiment, the polypeptide is 5mg to 15mg per dosage unit. In one embodiment, the polypeptide is 5mg to 10mg per dosage unit. In one embodiment, the polypeptide is 1mg per dosage unit. In one embodiment, the polypeptide is 2 mg/dosage unit. In one embodiment, the polypeptide is 3 mg/dosage unit. In one embodiment, the polypeptide is 4 mg/dosage unit. In one embodiment, the polypeptide is 5 mg/dosage unit. In one embodiment, the polypeptide is 6 mg/dosage unit. In one embodiment, the polypeptide is 7 mg/dosage unit. In one embodiment, the polypeptide is 8 mg/dosage unit. In one embodiment, the polypeptide is 9mg per dosage unit. In one embodiment, the polypeptide is 10 mg/dosage unit. In one embodiment, the polypeptide is 11 mg/dosage unit. In one embodiment, the polypeptide is 12 mg/dosage unit. In one embodiment, the polypeptide is 13 mg/dosage unit. In one embodiment, the polypeptide is 14 mg/dosage unit. In one embodiment, the polypeptide is 15 mg/dosage unit. In one embodiment, the polypeptide is 16 mg/dosage unit. In one embodiment, the polypeptide is 17 mg/dosage unit. In one embodiment, the polypeptide is 18 mg/dosage unit. In one embodiment, the polypeptide is 19 mg/dosage unit. In one embodiment, the polypeptide is 20mg per dosage unit.
In some embodiments of the invention, the protease inhibitor is one that reduces the hydrolytic activity of a protease on a protein or polypeptide.
In some embodiments of the invention, the protease inhibitor is a serine protease inhibitor. The serine protease inhibitors include, but are not limited to, antithrombin, alpha 1-antitrypsin, cortisol-binding globulin, thyroxine-binding globulin, angiotensinogen, antitrypsin-related proteins, monocyte neutrophil elastase inhibitors, and alpha 1-antitrypsin.
In some embodiments of the invention, the protease inhibitor is a trypsin inhibitor, including but not limited to bean extracted trypsin inhibitor.
In some embodiments of the invention, the protease inhibitor is soybean trypsin inhibitor (SBTI), lima bean trypsin inhibitor, aprotinin, or ovomucoid.
In some embodiments of the invention, the soybean trypsin inhibitor is a Bowman-Birk trypsin inhibitor and or a Kunitz trypsin inhibitor.
In one embodiment, the soybean trypsin inhibitor is from 0.1mg to 500mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is from 0.5mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 1mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 3mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 5mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 7mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is from 10mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 15mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 20mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 25mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 30mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 35mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 40mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 42mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 50mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 55mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 60mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 70mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 75mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 80mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 85mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 90mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 100mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 115mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 120mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 135mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 145mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 155mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 165mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 175mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 180mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 200mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 210mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 220mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 230mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 240mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 250mg to 300mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 20mg to 30mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 30mg to 40mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 40mg to 50mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 50mg to 60mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 60mg to 70mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 80mg to 90mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 90mg to 100mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 100mg to 105mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 110mg to 115mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 120mg to 125mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 130mg to 135mg per dosage unit. In one embodiment, the soybean trypsin inhibitor is 140mg to 145mg per dosage unit.
In some embodiments of the invention, the polypeptide composition further comprises a first resorptive agent. The first absorption enhancer may be a surfactant. Surfactants include, but are not limited to, ionic surfactants, nonionic surfactants, amphoteric surfactants. In some more specific embodiments, the ionic surfactant includes, but is not limited to, stearic acid, oleic acid, lauric acid, calcium stearate, higher fatty alcohol sulfates, fatty sulfonates. In some more specific embodiments, the nonionic surfactant includes, but is not limited to, one or a combination of a fatty acid glyceride, a sucrose fatty acid ester, a sorbitan fatty acid, a polysorbate, a polyoxyethylene fatty acid ester, a polyoxyethylene fatty alcohol ether, a polyoxyethylene-polyoxypropylene copolymer. In some more specific embodiments, the fatty acid glyceride includes, but is not limited to, fatty acid monoglyceride, fatty acid diglyceride, and fatty acid glyceride. In some more specific embodiments, the surfactant can be sucrose laurate, sodium lauryl sulfate, caprylic capric macrogol glyceride, a sulfhydryl polymer, an ionic liquid, glycerol monostearate, methyl cellulose, carboxymethyl cellulose, polyoxyethylene hydrogenated castor oil, lauryl alcohol, polyethylene glycol stearate, lecithin. In some more specific embodiments, the first prosorbent is tween 20.
In some embodiments of the invention, the first absorption enhancer may be a chelating agent, which may be ethylenediaminetetraacetic acid, ethyleneglycol tetraacetic acid, diethylenetriaminepentaacetic acid, ethatic acid, citrate, bile acid, cholic acid, chenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, 3 β -monohydroxycholic acid, lithocholic acid, 3 α -hydroxy-12-ketocholic acid, 3 β -hydroxy-12-ketocholic acid, 12 α -3 β -dihydrocholic acid, ursodeoxycholic acid, or an alkali metal. In some more specific embodiments, the chelating agents can be combined in two or any combination, and the ratio can be adjusted.
In one embodiment, the first absorption enhancer is from 0.1mg to 30mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 20mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 15mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 10mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 5mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 4mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 3.5mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 3mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 2.5mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 2mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 1.5mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 1.0mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 0.5mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.1mg to 0.3mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.5mg to 5mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.5mg to 4mg per dosage unit. In one embodiment, the first absorption enhancer is from 0.5mg to 3mg per dosage unit.
In some embodiments of the invention, the polypeptide composition further comprises a second resorptive agent, which is a surfactant. Surfactants include, but are not limited to, ionic surfactants, nonionic surfactants, amphoteric surfactants.
In some more specific embodiments, the ionic surfactant includes, but is not limited to, stearic acid, oleic acid, lauric acid, calcium stearate, higher fatty alcohol sulfates, fatty sulfonates.
In some more specific embodiments, the nonionic surfactant includes, but is not limited to, one or a combination of a fatty acid glyceride, a sucrose fatty acid ester, a sorbitan fatty acid, a polysorbate, a polyoxyethylene fatty acid ester, a polyoxyethylene fatty alcohol ether, a polyoxyethylene-polyoxypropylene copolymer. In some more specific embodiments, the fatty acid glyceride includes, but is not limited to, fatty acid monoglyceride, fatty acid diglyceride, and fatty acid glyceride.
In some more specific embodiments, the surfactant can be sucrose laurate, sodium lauryl sulfate, caprylic/capric macrogol glyceride, a sulfhydryl polymer, an ionic liquid, glycerol monostearate, methylcellulose, carboxymethylcellulose, polyoxyethylene hydrogenated castor oil, lauryl alcohol, polyethylene glycol stearate, lecithin, sodium lauryl sulfate, a sulfhydryl polymer, an ionic liquid, a sodium stearate, a sodium lauryl sulfate, a sodium carboxymethyl cellulose, a polyoxyethylene hydrogenated castor oil, a polyoxyethylene hydrogenated castor oil, a polyoxyethylene lauryl sulfate, a lecithin, a polyoxyethylene lauryl sulfate, a,
In some more specific embodiments, the polypeptide composition further comprises a second pro-absorbent agent that is a polyoxyethylene sorbitan fatty acid ester.
The first absorption promoting agent and the second absorption promoting agent act synergistically to protect the polypeptide from gastrointestinal damage, thereby achieving oral administration.
In some embodiments of the invention, the polyoxyethylene sorbitan fatty acid ester is tween 20, tween 40, tween 60, tween 65, or tween 80 (tween-80). In some more specific embodiments tween 60 and or tween 80.
In one embodiment, the tween 80 is between 1mg and 40mg per dosage unit. In one embodiment, the tween 80 is between 1mg and 35mg per dosage unit. In one embodiment, the tween 80 is between 1mg and 30mg per dosage unit. In one embodiment, the tween 80 is between 1mg and 25mg per dosage unit. In one embodiment, the tween 80 is between 1mg and 20mg per dosage unit. In one embodiment, the tween 80 is between 1mg and 15mg per dosage unit. In one embodiment, the tween 80 is between 1mg and 10mg per dosage unit. In one embodiment, the tween 80 is between 1mg and 5mg per dosage unit. In one embodiment, the tween 80 is between 5mg and 10mg per dosage unit. In one embodiment, the tween 80 is between 10mg and 15mg per dosage unit. In one embodiment, the tween 80 is between 15mg and 20mg per dosage unit. In one embodiment, the tween 80 is between 20mg and 25mg per dosage unit. In one embodiment, the tween 80 is between 25mg and 30mg per dosage unit. In one embodiment, the tween 80 is between 20mg and 30mg per dosage unit.
In some embodiments of the invention, the polypeptide in the polypeptide composition: the soybean trypsin inhibitor comprises: the first absorption enhancer is: the weight ratio of the second absorption promoting agent is 1: (9-40): (0.1-0.7): (0.8-6).
In some more specific embodiments, the polypeptide: the soybean trypsin inhibitor comprises: the first absorption enhancer is: the weight ratio of the second absorption promoting agent is 1: 9: 0.1: 0.8 or 1: 40: 0.7: 6.
in one embodiment, the polypeptide composition further comprises EDTA or a salt thereof. The EDTA is 0.1 mg-400 mg/dosage unit. In one embodiment, the EDTA is between 0.1mg and 350mg per dosage unit. In one embodiment, the EDTA is between 0.1mg and 300mg per dosage unit. In one embodiment, the EDTA is between 0.5mg and 250mg per dosage unit. In one embodiment, the EDTA is between 1mg and 200mg per dosage unit. In one embodiment, the EDTA is between 3mg and 200mg per dosage unit. In one embodiment, the EDTA is between 5mg and 200mg per dosage unit. In one embodiment, the EDTA is 7mg to 200mg per dosage unit. In one embodiment, the EDTA is between 10mg and 200mg per dosage unit. In one embodiment, the EDTA is 15mg to 200mg per dosage unit. In one embodiment, the EDTA is between 20mg and 200mg per dosage unit. In one embodiment, the EDTA is 25mg to 200mg per dosage unit. In one embodiment, the EDTA is 30mg to 200mg per dosage unit. In one embodiment, the EDTA is 35mg to 200mg per dosage unit. In one embodiment, the EDTA is 40mg to 200mg per dosage unit. In one embodiment, the EDTA is 42mg to 200mg per dosage unit. In one embodiment, the EDTA is between 50mg and 200mg per dosage unit. In one embodiment, the EDTA is between 55mg and 200mg per dosage unit. In one embodiment, the EDTA is between 60mg and 200mg per dosage unit. In one embodiment, the EDTA is 70mg to 200mg per dosage unit. In one embodiment, the EDTA is between 75mg and 200mg per dosage unit. In one embodiment, the EDTA is 80mg to 200mg per dosage unit. In one embodiment, the EDTA is 85mg to 200mg per dosage unit. In one embodiment, the EDTA is between 90mg and 200mg per dosage unit. In one embodiment, the EDTA is between 100mg and 200mg per dosage unit. In one embodiment, the EDTA is present in an amount of 115mg to 200mg per dosage unit. In one embodiment, the EDTA is between 120mg and 200mg per dosage unit. In one embodiment, the EDTA is 135mg to 200mg per dosage unit. In one embodiment, the EDTA is 145mg to 200mg per dosage unit. In one embodiment, the EDTA is 155mg to 200mg per dosage unit. In one embodiment, the EDTA is 165mg to 200mg per dosage unit. In one embodiment, the EDTA is 175mg to 200mg per dosage unit. In one embodiment, the EDTA is between 180mg and 200mg per dosage unit. In one embodiment, the EDTA is 200mg to 200mg per dosage unit. In one embodiment, the EDTA is present in an amount of from 210mg to 200mg per dosage unit. In one embodiment, the EDTA is 220mg to 200mg per dosage unit. In one embodiment, the EDTA is between 230mg and 200mg per dosage unit. In one embodiment, the EDTA is 240mg to 200mg per dosage unit. In one embodiment, the EDTA is between 250mg and 200mg per dosage unit. In one embodiment, the EDTA is between 20mg and 30mg per dosage unit. In one embodiment, the EDTA is between 30mg and 40mg per dosage unit. In one embodiment, the EDTA is between 40mg and 50mg per dosage unit. In one embodiment, the EDTA is 50mg to 60mg per dosage unit. In one embodiment, the EDTA is between 60mg and 70mg per dosage unit. In one embodiment, the EDTA is 80mg to 90mg per dosage unit. In one embodiment, the EDTA is between 90mg and 100mg per dosage unit. In one embodiment, the EDTA is between 100mg and 105mg per dosage unit. In one embodiment, the EDTA is 110mg to 115mg per dosage unit. In one embodiment, the EDTA is between 120mg and 125mg per dosage unit. In one embodiment, the EDTA is between 130mg and 135mg per dosage unit. In one embodiment, the EDTA is between 140mg and 145mg per dosage unit.
In some embodiments of the invention, the polypeptide composition further comprises fish oil.
In some embodiments of the invention, the polypeptide composition further comprises an enteric coating, gelatin coating, or film coating. The coating inhibits digestion of the polypeptide composition in the gastrointestinal tract of the subject.
In one embodiment, the coating may be hydroxypropylmethyl cellulose, hydroxypropyl cellulose, acrylic resin, polyvinyl pyrrolidone. In one embodiment, the coating may be ethyl cellulose, cellulose acetate.
In one embodiment, the coating is an acrylic polymer
As an enteric coating. In one embodiment, the coating is a dispersion of ethyl cellulose. In one embodiment, the coating is a chitosan, degradable polysaccharide. In one embodiment, the coating is a pH sensitive coating.
In some embodiments of the invention, the polypeptide composition may further include additives in amounts commonly used, including, but not limited to, plasticizers, preservatives, colorants, lubricants, flavorants, excipients, diluents, flavorants, solubilizers, and the like.
In some embodiments of the invention, the polypeptide composition may be prepared by conventional methods, such as mixing thymalfasin with a first absorption enhancer and a second absorption enhancer, adding soybean trypsin inhibitor, mixing, encapsulating, and enteric coating. The coating material can comprise Eudragit L-100, Talc and polyethylene glycol, the coating material is dissolved by dichloromethane and isopropanol to obtain a coating solution, and the coating solution is sprayed on the surface of the capsule to obtain the enteric capsule.
In some embodiments of the invention, the polypeptide composition is administered orally either once daily, 2 times daily, three times daily, once weekly, or cyclically, such as by stopping administration for a period of time after several days or weeks.
In some embodiments of the invention, the dosage form of the polypeptide composition may be any known dosage form. Such as solid or liquid dosage forms. Such as tablet, soft capsule, powder, granule, capsule, pill, suppository, ointment, gel, aerosol, membrane, syrup, emulsion, suspension or injection.
In some embodiments of the invention, the invention provides the use of the polypeptide composition for the manufacture of a medicament for administration to a human subject. In some embodiments, the invention provides application of the polypeptide composition in preparing a medicament for preventing or treating hepatitis B and enhancing immune response.
3. Advantageous effects
Compared with the prior art, the invention has the beneficial effects that:
(1) the polypeptide composition can realize oral administration of the thymosin, and is not damaged by the gastrointestinal tract.
Detailed Description
The present invention is described in detail below.
Example 1
Preparation of thymalfasin enteric-coated capsule
Preparing a coating solution:
3.0mg of Eudragit L-100, 2.0mg of Talc and 1.5mg of polyethylene glycol were dissolved with an appropriate amount of methylene chloride and isopropyl alcohol to obtain a coating solution.
Preparing an enteric capsule:
mixing thymalfasin with tween 80 (or tween 20 and tween 80 if the composition contains tween 20), adding SBTI, mixing, encapsulating, and spraying the coating solution onto the surface of the capsule to obtain thymalfasin enteric-coated capsule. SBTI is a soybean trypsin inhibitor.
Example 2
Enteric capsules of the following compositions were prepared as in example 1
Composition A, 3mg thymalfasin;
composition B: 3mg thymalfasin +120mg SBTI +2.1mg Tween 20;
composition C: 3mg thymalfasin +120mg SBTI +18mg Tween 80;
composition D: 3mg thymalfasin +120mg SBTI +2.1mg Tween 20+18mg Tween 80;
composition E: 3mg thymalfasin +27mg SBTI +0.3mg Tween 20;
composition F: 3mg thymalfasin +27mg SBTI +2.4mg Tween 80;
composition G: 3mg of thymalfasin, 27mg of SBTI, 0.3mg of Tween 20 and 2.4mg of Tween 80.
SBTI is a soybean trypsin inhibitor. It will be appreciated by those skilled in the art that SBTI may be Bowman-Birk trypsin inhibitor or Kunitz trypsin inhibitor or a combination of both.
The above compositions were administered to rhesus monkeys as follows, and the monkeys were grouped, each group of monkeys administered the corresponding composition enteric capsules, 1 capsule per monkey. The rhesus monkey is prohibited from eating for 12h before administration, and kept awake. The enteric-coated capsules were administered orally by gavage tube, 15ml of water being added after administration.
Blood samples were collected at 0, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h after administration. Plasma thymalfasin concentrations were determined by the kit. The resulting plasma thymalfasin concentrations are compiled into the tables.
TABLE 1,
TABLE 2,
TABLE 3,
TABLE 4,
TABLE 5,
TABLE 6,
TABLE 7,
As can be seen from the data in the statistical analysis table,
enteric capsules of composition a were taken orally with the active ingredient thymalfasin totally destroyed by the gastrointestinal tract.
The thymalfasin composition enteric-coated capsule is orally taken, wherein the active ingredient thymalfasin is completely damaged by gastrointestinal tracts.
The composition enteric-coated capsule orally taking thymalfasin, SBTI and Tween 80 has the advantages that the active ingredient thymalfasin is mostly damaged by gastrointestinal tracts, the maximum blood concentration is reached within 2.5 hours, and the mean value of the blood concentration Cmax is 11.5 ng/ml-21 ng/ml.
The oral thymalfasin + SBTI + Tween 20+ Tween 80 composition enteric-coated capsule has the active ingredient thymalfasin reaching the maximum blood concentration within 2.5h, and the mean value of the blood concentration Cmax is 57.5 ng/ml-112.5 ng/ml. Therefore, the Tween 20 and the Tween 80 play a synergistic role, play an unexpected role and greatly enhance the absorption of the thymalfasin in the gastrointestinal tract.
Claims (7)
1. A polypeptide composition, which comprises a therapeutically effective amount of polypeptide, soybean trypsin inhibitor, a first absorption promoting agent and a second absorption promoting agent, wherein the effective amount of polypeptide is thymalfasin, the first absorption promoting agent is tween 20, and the second absorption promoting agent is tween 80;
the polypeptide: the soybean trypsin inhibitor comprises: the first absorption enhancer is: the weight ratio of the second absorption promoting agent is 1: (9-40): (0.1-0.7): (0.8-6).
2. The polypeptide composition of claim 1, wherein the soybean trypsin inhibitor is Bowman-Birk trypsin inhibitor and or Kunitz trypsin inhibitor.
3. The polypeptide composition of claim 1, wherein the polypeptide: the soybean trypsin inhibitor comprises: the first absorption enhancer is: the weight ratio of the second absorption promoting agent is 1: 9: 0.1: 0.8 or 1: 40: 0.7: 6.
4. the polypeptide composition of claim 1, further comprising an enteric coating or gelatin coating.
5. An oral composition comprising the polypeptide composition of any one of claims 1-4 and an additive which is a plasticizer, preservative, colorant, lubricant, flavoring agent, excipient, diluent, flavoring agent, or solubilizing agent.
6. Use of the polypeptide composition of any one of claims 1-4 or the oral composition of claim 5 for the preparation of a medicament for the prevention or treatment of hepatitis b.
7. Use of the polypeptide composition of any one of claims 1-4 or the oral composition of claim 5 for the preparation of a medicament for enhancing an immune response.
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| WO1998009645A1 (en) * | 1996-09-04 | 1998-03-12 | Dott Research Laboratory | Peptide-containing drug compositions for oral administration |
| WO2009118722A2 (en) * | 2008-03-26 | 2009-10-01 | Oramed Pharmaceuticals, Inc. | Methods and compositions for oral administration of proteins |
| CN101380461A (en) * | 2008-09-27 | 2009-03-11 | 吴建中 | Efficient thymosin enteric-coated tablets and thymosin for injection |
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