A kind of intestinal administration carrier thiolated calcium alginate microspheres and preparation method thereof

A drug delivery carrier, calcium alginate technology, applied in pharmaceutical formulations, microcapsules, drug delivery, etc., can solve the problems of endangering the health of patients, high drug concentration, and weak adhesion, so as to increase the residence time and strengthen the mucous membrane Adhesion, effect of increasing cycle time

Inactive Publication Date: 2020-07-28
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, when used as a drug carrier, the sudden release of sodium alginate is too obvious. Calcium alginate microspheres prepared by the traditional emulsification method usually release 80% of the drug within 20 minutes, resulting in high drug concentration and even harm to patient health
In addition, the P-gp transporter widely present on the cells of the gastrointestinal tract is a drug efflux transporter, which allows the drugs that have entered the cells to be effluxed out, thus limiting the oral absorption of many exogenous drugs and reducing the drug bioavailability
[0004] Sodium alginate adheres to the small intestinal mucosa through non-covalent bonds such as van der Waals force, hydrogen bond and electrostatic attraction, so its adhesion is not strong compared with covalent bonds

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Prepare a sodium alginate aqueous solution with a mass concentration of 1%, add 5mL of a 30mM carbodiimide aqueous solution and stir for 45min, then add 1g of L-cysteine ​​and mix well, and adjust the pH of the above mixed solution to 5. Stir and react in the dark at room temperature for 3 hours, dialyze twice in 8000~14000kDa dialysis bags with 1mM hydrochloric acid solution as the outer fluid for dialysis, then dialyze twice with 1mM hydrochloric acid solution containing 1% sodium chloride as the outer fluid for dialysis, and finally Dialyze twice with 1mM hydrochloric acid solution as the dialysis external fluid, each dialysis time is 12~24h, and the reaction solution obtained after dialysis is freeze-dried to prepare the L-cysteine-sodium alginate conjugate; the sodium alginate and the L-cysteine-sodium alginate conjugate with a sulfhydryl content of 400 μmol / g were uniformly mixed at a mass ratio of 3:1, and then prepared into a mixed aqueous solution with a mass co...

Embodiment 2

[0023] Dissolve 7g of sodium alginate in 50mL of water, then add 3g of thioglycolic acid and 2mL of 7M hydrochloric acid solution, stir and react at 80°C for 2.5h in the dark, then pour the resulting reaction mixture into 250mL of ethanol, filter and dissolve The precipitate was washed twice with ethanol, and dried at room temperature to prepare the thioglycolic acid-sodium alginate conjugate. Sodium alginate and thioglycolic acid-sodium alginate conjugate with a mercapto group content of 300 μmol / g were uniformly mixed at a mass ratio of 2:1, and then prepared into a mixed aqueous solution with a mass concentration of 1% as a dispersed phase; peanut oil and Petroleum ether is mixed at a volume ratio of 10:6, and then propylene glycol monostearate accounting for 3% of the mass of the mixed oil phase is added as the continuous phase; 1 volume part of the dispersed phase is added dropwise to 13 volume parts of the continuous phase, and the Emulsify at 300rpm for 45min, then add ...

Embodiment 3

[0025] Prepare a sodium alginate aqueous solution with a mass concentration of 3%, add 5mL of a 45mM carbodiimide aqueous solution and stir for 45min, then add 3g of N-acetylcysteine ​​and mix well, and adjust the pH of the above mixed solution with 1M hydrochloric acid solution To 5, stir and react at room temperature for 3 hours, then dialyze twice in 8000~14000kDa dialysis bags with 1mM hydrochloric acid solution as the external fluid for dialysis, and then dialyze twice with 1mM hydrochloric acid solution containing 1% sodium chloride as the external fluid for dialysis. Finally, 1mM hydrochloric acid solution was used as the dialysis external fluid for dialysis twice, each dialysis time was 12-24h, and the reaction solution obtained after dialysis was freeze-dried to prepare N-acetylcysteine-sodium alginate conjugate; seaweed Sodium acid and N-acetylcysteine-sodium alginate conjugated with a thiol content of 267 μmol / g were uniformly mixed at a mass ratio of 4:1, and then p...

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PUM

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Abstract

The invention relates to sulfhydrylation calcium alginate microspheres as an intestinal drug delivery carrier and a preparation method of the sulfhydrylation calcium alginate microsphere. The method comprises the following steps: mixing sodium alginate with sulfhydrylation calcium alginate according to the mass ratio of (1 to 8) to 1 and preparing a solution with the mass concentration of 0.5 to 5percent, then adding an oil phase containing a surfactant and emulsifying at room temperature at 200 to 900 rpm for 45 minutes, adding CaCl2 powder and continuously stirring at 100 to 400 rpm for 0.5to 3 hours to realize cross-linking and solidifying of the microspheres, carrying out centrifugal demulsification, washing and then screening the microspheres to obtain the sulfhydrylation calcium alginate microspheres. The sulfhydrylation calcium alginate microspheres prepared with an emulsification method disclosed by the invention have uniform and controllable particle size and good monodispersity. The prepared sulfhydrylation calcium alginate microspheres have strong mucosal adhesion properties in small intestine and can prolong the residence time of the microspheres in the intestine, sothat the long-acting administration effect is achieved. Therefore, the sulfhydrylation calcium alginate microspheres prepared with the preparation method disclosed by the invention have potential market application prospects in the fields of a drug delivery system for bioactive drugs such as protein, polypeptide and the like as well as intestinal targeted drug delivery.

Description

technical field [0001] The invention relates to the field of biomedical materials, in particular to a thiolated calcium alginate microsphere, a carrier for intestinal drug delivery, with uniform and controllable particle size, good monodispersity, and good intestinal adhesion and pH responsiveness. its preparation method. Background technique [0002] With the rapid development of biomedical technology, bioactive macromolecular drugs such as proteins, peptides and enzymes are used for the diagnosis or treatment of cancer, cardiovascular and other diseases. Macromolecular drugs often enter the human body through intravenous injection, which can cause physical pain and psychological panic to patients. Non-intravenous injections such as oral administration will reduce the bioavailability of drugs, because protein or polypeptide drugs will be degraded by pepsin and trypsin in the gastrointestinal tract and lose their activity after oral administration, so they cannot reach the ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/52A61K47/36A61K47/20
CPCA61K9/5015A61K9/5036
Inventor 李德富毛新艳袁柳青朱桂莹岑能凯
Owner SICHUAN UNIV
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