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Polypeptide-calcitonin supramolecular aggregate with slow-release performance and preparation method thereof

A technology of supramolecular aggregates and sustained release performance, applied in the field of biomedicine, can solve the problems of high injection frequency, patient pain, short half-life, etc., and achieve the effects of good biocompatibility, guaranteed biological activity, and mild process conditions.

Active Publication Date: 2015-04-29
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] At present, the dosage form of calcitonin on the market is mainly injection, and its main component is calcitonin monomer, and the administration method is subcutaneous injection. However, since calcitonin is a polypeptide drug, its half-life is very short, and the commonly used injections are generally The highest plasma concentration can be reached 1 hour after subcutaneous injection, and the metabolism is almost complete after 3 hours of injection, so the injection frequency is very high, and frequent injection will bring great pain and inconvenience to the patient

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  • Polypeptide-calcitonin supramolecular aggregate with slow-release performance and preparation method thereof
  • Polypeptide-calcitonin supramolecular aggregate with slow-release performance and preparation method thereof
  • Polypeptide-calcitonin supramolecular aggregate with slow-release performance and preparation method thereof

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Embodiment 1

[0039] figure 1It is a schematic diagram of the formation process of the polypeptide-calcitonin supramolecular aggregate with slow-release performance described in the present invention, and the process steps of this embodiment are as follows:

[0040] (1) Add 8 g of salmon calcitonin and 4 g of amphiphilic polypeptide with amino acid sequence Asp-Phe (aspartic acid-phenylalanine) into a 50 mL round-bottomed flask equipped with a magnetic stir bar, and then add Add 20 mL of sodium phosphate buffer solution with pH=7.0 to form a mixed solution, the concentration of the salmon calcitonin in the mixed solution is 400 mg / mL, and the concentration of the amphiphilic polypeptide in the mixed solution is 200 mg / mL;

[0041] (2) Put the round-bottomed flask containing the mixed solution into a water bath on a constant temperature magnetic stirrer, the temperature of the water bath is 60°C, and then stir at a speed of 180r / min for 0.5h. After the stirring time expires, the supramolecul...

Embodiment 2

[0045] figure 1 It is a schematic diagram of the formation process of the polypeptide-calcitonin supramolecular aggregate with slow-release performance described in the present invention, and the process steps of this embodiment are as follows:

[0046] (1) Add 680 mg of salmon calcitonin and 1.94 g of the amphiphilic polypeptide whose amino acid sequence is shown in SEQ ID No: 5 in the sequence listing to a 50 mL round bottom flask equipped with a magnetic stirrer, and then add pH = 20 mL of sodium phosphate buffer solution of 5.0 forms a mixed solution, the concentration of the salmon calcitonin in the mixed solution is 34 mg / mL, and the concentration of the amphiphilic polypeptide in the mixed solution is 97 mg / mL;

[0047] (2) Put the round-bottomed flask containing the mixed liquid into a water bath on a constant temperature magnetic stirrer. The temperature of the water bath is 5°C, and then stir at a speed of 2000r / min for 1h. After the stirring time expires, supramolec...

Embodiment 3

[0051] figure 1 It is a schematic diagram of the formation process of the polypeptide-calcitonin supramolecular aggregate with slow-release performance described in the present invention, and the process steps of this embodiment are as follows:

[0052] (1) Add 0.2 g of salmon calcitonin and 0.2 g of the amphiphilic polypeptide whose amino acid sequence is shown in SEQ ID No: 1 in the sequence listing to a 50 mL round bottom flask equipped with a magnetic stirrer, and then add pH =8.0 sodium phosphate buffer 20mL forms a mixed solution, the concentration of the salmon calcitonin in the mixed solution is 10mg / mL, and the concentration of the amphiphilic polypeptide in the mixed solution is 10mg / mL;

[0053] (2) Put the round-bottomed flask containing the mixed liquid into a water bath on a constant temperature magnetic stirrer, the temperature of the water bath is 25°C, and then stir at a speed of 180r / min for 24h. After the stirring time expires, supramolecular aggregation is ...

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Abstract

The invention belongs to the field of biological medicines, and provides a polypeptide-calcitonin supramolecular aggregate with slow-release performance. The aggregate consists of calcitonin and amphiphilic polypeptide, wherein the calcitonin and the amphiphilic polypeptide are aggregated into nano-grade particles by means of hydrophilic and hydrophobic interaction and positive and negative charge interaction. The preparation method comprises the following steps: (1) dissolving calcitonin and amphiphilic polypeptide in a solvent which has a pH value of 5-10 to form mixed liquid; (2) standing the mixed liquid at 5-60 DEG C for 1-300 hours or stirring for 1-300 hours to form the polypeptide-calcitonin supramolecular aggregate. The supramolecular aggregate can slowly release calcitonin, and can be used for greatly prolonging the time of blood calcium concentration in a body at a normal level after single administration, so that the injection frequency can be reduced.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular to a polypeptide-calcitonin supramolecular aggregate with slow-release performance and a preparation method thereof. Background technique [0002] Skeleton is an important part of the human body. It constitutes the frame of the human body and plays the role of protection, support and movement. It is also closely related to the metabolism of mineral elements such as calcium and phosphorus in the body. During a person's life, bones are constantly undergoing metabolism. Bone metabolism includes two aspects: bone formation and bone resorption. Under normal circumstances, they are in a state of dynamic balance, but external factors or hormone secretion disorders in the body will cause Lead to abnormal bone metabolism, leading to diseases such as osteoporosis and osteitis deformans. With the increase of the elderly population in our country, the incidence of osteoporosis is on the rise, and it...

Claims

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Application Information

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IPC IPC(8): A61K38/23A61K9/14A61K47/42A61K47/18A61P5/18A61P19/08A61P19/10
Inventor 李建树曹叔琴
Owner SICHUAN UNIV
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