Hydrophobic drug containing polyelectrolyte complex, its preparation method and application thereof

A hydrophobic drug and polyelectrolyte technology, which is used in non-active ingredients in medical preparations, pharmaceutical formulations, powder delivery, etc., can solve the problem of poor mucoadhesion of nanoparticle carriers, affecting the human immune system, and developing drug resistance in the human body. problems, to achieve the effect of increasing bioavailability, prolonging residence time, and reducing pain

Inactive Publication Date: 2012-12-12
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are also some polyester (PLGA) or PEG-polyester amphiphilic copolymers used in the oral study of hydrophobic drugs. The nanoparticle carriers formed by such polymers have poor mucoadhesion, and their oral bioavailability has always been low. When used together with P-gp inhibitors, these inhibitors will affect the human immune system and make the human body develop drug resistance (D.R.Kalaria, G.Sharma, V.Beniwal, M.N.V.Ravi Kumar, Pharmaceutical Research, 2009, 26:492-501 )
[0004] The use of pH-sensitive nanoparticles formed by electrostatic complexation of chitosan and polyglutamic acid for oral administration of hydrophilic drugs such as insulin has been extensively studied (Y.H.Lin, K.Sonaje, K.M.Lin, J.H.Juang, F.L.Mi, H.W.Yang, H.W.Sung, Journal of Controlled Release, 2008,132:141-149), at pH 3.0-6.0, two polyelectrolytes form nanoparticles to encapsulate the drug inside the nanoparticles, and the nanoparticles disintegrate at pH 7.4 release drugs, but the use of polyelectrolyte nanoparticles for the release of hydrophobic drugs has rarely been reported

Method used

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  • Hydrophobic drug containing polyelectrolyte complex, its preparation method and application thereof
  • Hydrophobic drug containing polyelectrolyte complex, its preparation method and application thereof
  • Hydrophobic drug containing polyelectrolyte complex, its preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 (I-1):

[0039] Polyanion linked to drug ester bond:

[0040] Add 0.1 g of poly-L-glutamic acid (L-PGA) (number-average molecular weight 6500 Da), 0.13 g of paclitaxel (PTX) and 82.52 mg of dicyclohexylcarbodiimide (DCC) to a dry reaction vial, dimethyl formaldehyde The amide (DMF) was dissolved and finally 48.87 mg of 4-dimethylaminopyridine (DMAP) was added. Evacuate and fill with nitrogen. Reaction at room temperature for 24h. The reaction solution was dialyzed in DMF for 24 hours, then in distilled water for 24 hours, and then the product was freeze-dried for 24 hours to obtain the target product of polyglutamic acid ester-bonded drug L-PGA-PTX (abbreviated as I-1).

Embodiment 2~10

[0041] Examples 2-10: According to the method of Example 1, the polyanions (I-2~I-11) with a variety of bonded drugs can be obtained by changing the type of polyanion, drug and the amount of drug bonding. The specific parameters are shown in the table 1.

[0042] Table 1 Polyanions of ester-bonded drugs

[0043] Example

[0044] Drug-PA: a polyanion bound to a drug; M n : number-average relative molecular mass of the polyanion; N 0 : the molar ratio of the drug to the anion group of the polyanion in the reaction; N: the molar ratio of the anion group of the drug to the polyanion in the product; γ-PGA: γ-polyglutamic acid; HA: hyaluronic acid; SA: Sodium alginate; PAC: carboxy-modified cellulose; PTX: paclitaxel; DEX: dexamethasone; NPs: drug-containing polyanionic nanoparticles

Embodiment 11

[0045] Example 11 The polyanion of ester bond bonded cisplatin

[0046] 30 mg of cisplatin was dissolved in 20 mL of deionized water, mixed with 10 mL of an aqueous solution containing 100 mg of L-PGA, and reacted for 24 hours at 37° C. in the dark with stirring. The reaction solution was dialyzed for 2 days and freeze-dried to obtain 97 mg of white powder of HA-CDDP macromolecule anticancer drug, with a yield of 74.6%.

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Abstract

The invention relates to a hydrophobic drug containing polyelectrolyte complex, its preparation method and an application thereof. The polyelectrolyte complex is formed by static compounding of polycation and electronegative nanoparticles formed by polyanion or its derivative entrapment or linkage of a hydrophobic drug. The particle size of the polyelectrolyte complex is 20-500 nm. The positive / negative charge ratio of the polycation to the polyanion is between 1.2 and 6.0. According to the drug-containing complex formed by static compounding, an external positive charge shell can protect stability of the complex in a gastric acidic environment, and in an intestinal alkaline environment, the complex disintegrates and releases the internal anion drug loaded nanoparticles so as to promote absorption of the drug through intestinal mucosa. In addition, the polycation shell has mucosa adhesiveness and retention time of the drug in gastrointestinal mucosa can be prolonged. Therefore, the complex is suitable for oral administration of hydrophobic drugs. Bioavailability of the hydrophobic drugs is increased, and pains caused by injection delivery can be minimized for patients.

Description

technical field [0001] The invention relates to a polyelectrolyte complex containing hydrophobic drugs, a preparation method and application thereof, and belongs to the application technology of polymer materials in pharmaceutical preparations. Background technique [0002] Oral drug delivery can provide convenience for patients, reduce the cost of drug delivery and facilitate the implementation of more long-term treatment options. Before being absorbed, the drug must be dissolved in the digestive juice of the gastrointestinal tract, and then it can pass through the gastrointestinal mucosa and enter the blood circulation through absorption mechanisms such as passive diffusion or active transport. The dissolution of poorly soluble drugs in digestive juices is usually the rate-limiting stage of their absorption. Therefore, improving the solubility and dissolution rate of insoluble drugs is often the first step to improve their oral bioavailability. Traditional pharmaceutical ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K9/19A61K47/59A61K47/61A61K47/62
Inventor 董岸杰蔺晓娜肖燕刘文清邓联东
Owner TIANJIN UNIV
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