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Lipid preparation containing insoluble camptothecin drug and preparation method thereof

A technology of liposome preparations and camptothecin, which is applied in the field of pharmaceutical preparations, can solve the problems of low liposome encapsulation efficiency and poor affinity, and achieve the effect of improving encapsulation efficiency, simple preparation method, and improving encapsulation efficiency

Inactive Publication Date: 2012-09-19
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But because water-insoluble camptothecin drugs are usually water-insoluble and fat-insoluble, and have poor affinity with lipids such as phospholipids, the encapsulation efficiency of liposomes prepared by the above method is usually low, no more than 50%.
For this reason, patent CN1562021A discloses a kind of method that improves encapsulation efficiency by adjusting the pH of external phase, this method is at first this class medicine is dissolved in alkaline solution, after encapsulating into liposome with solution (ring opening) form then Then adjust the pH of the external phase to make the camptothecin drugs become precipitated (closed ring) and be wrapped in the liposome, thereby improving the encapsulation efficiency of the drug, but this method is still limited to encapsulation efficiency from 10% to 10% of the prior art. 30% increase to above 75%

Method used

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  • Lipid preparation containing insoluble camptothecin drug and preparation method thereof
  • Lipid preparation containing insoluble camptothecin drug and preparation method thereof
  • Lipid preparation containing insoluble camptothecin drug and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 110

[0037] The preparation of embodiment 110-hydroxycamptothecin long circulation thermosensitive liposome

[0038] Prepare liposomes by film dispersion-homogeneous membrane-passing method: 10-hydroxycamptothecin 1g, DPPC (dipalmitoyl lecithin) 46g, distearylethanolamine-polyethylene glycol 2000 3.0g, dissolve in chloroform : Methanol = 1:1, sonicate until completely dissolved, 55°C, 150rpm rotary evaporation for 40min to remove the organic solvent, vacuum-dry for 3h, add 0.3M, pH5.0 sodium phosphate salt solution containing 500mg / ml trehalose After hydration at 50°C and 100rpm for 40 minutes, homogenize through a 0.15 μm polycarbonate membrane, and then divide the mixture after passing through a 0.22 μm membrane into two parts, one for direct storage and use, and the other for freeze-thawing as follows After storage and use, the long-circulation thermosensitive liposome of 10-hydroxycamptothecin can be obtained.

[0039] Freeze-thaw procedure:

[0040] Freeze-Thaw Program -70°C...

Embodiment 210

[0042] The preparation of embodiment 210-hydroxycamptothecin liposomes

[0043] Dissolve 2 g of 10-hydroxycamptothecin, 47.5 g of egg yolk lecithin, and 0.5 g of vitamin E in chloroform:methanol=2:1, sonicate until completely dissolved, and rotatively evaporate at 45°C and 150 rpm for 40 minutes to remove the organic solvent, vacuum Dry for 3 hours, add 0.5M sodium phosphate solution with pH 5.0 containing 400mg / ml sucrose, hydrate at 45°C and 100rpm for 40min, homogenize through a 0.10μm polycarbonate membrane, and store for use after repeated freezing and thawing , to obtain 10-hydroxycamptothecin liposomes.

Embodiment 39

[0044] The preparation of embodiment 39-aminocamptothecin long circulation liposome

[0045] Dissolve 4g of 9-aminocamptothecin, 43g of egg yolk lecithin, 2.5g of distearylethanolamine-polyethylene glycol, and 0.5g of cholesterol in chloroform:methanol=2:1, sonicate until completely dissolved, 50°C, 150rpm Rotary evaporation at a rotating speed of 40 min to remove the organic solvent, vacuum drying for 3 h, adding 0.7 M sodium phosphate solution containing 300 mg / ml sucrose, pH 5.0, hydration at 45 °C and 100 rpm for 40 min, and homogenizing through 0.10 μm poly The carbonate membrane is stored and used after repeated freezing and thawing to obtain 9-aminocamptothecin long-circulating liposomes.

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Abstract

The invention relates to a lipid preparation containing an insoluble camptothecin drug and a preparation method of the lipid preparation. The lipid preparation comprises the insoluble camptothecin drug, phospholipid, salt, and sugar or polyol. The salt is selected from buffer salt and / or inorganic salt, and has concentration of 0.1-1.0 mol / L, preferably 0.3-0.8 mol / L. The sugar or polyol is selected from sucrose, trehalose, glucose, sorbose, lactose, fructose, sorbitol and mannitol, and has concentration of 200-1,000 mg / mL, preferably 300-800 mg / mL. The invention also relates to a medicinal composition containing the lipid preparation, and an application of the lipid preparation in preparation of anti-tumor drugs. The lipid preparation has the advantages of high encapsulation rate, simple and convenient preparation, and suitability for mass production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a liposome preparation containing insoluble camptothecin drugs and a preparation method thereof. Background technique [0002] Camptothecin or its derivatives, also known as camptothecin drugs, are DNA synthesis inhibitors used in the treatment of various cancer diseases. The varieties of camptothecin drugs currently on the market include camptothecin, 9-hydroxycamptothecin, 9-aminocamptothecin, 10-hydroxycamptothecin, nitrocamptothecin, 7-(β-trimethylformazine Silyl)ethylcamptothecin, 7-(tert-butoxy)iminomethylcamptothecin, 7-ethyl-10-hydroxycamptothecin (SN-38), 9-nitrocamptothecin ( 9-NC), etc., mainly through intravenous, oral, spraying and other modes of administration. [0003] Camptothecin drugs use topoisomerase as the site of action, and exert anti-cancer effects by inhibiting DNA synthesis. They are suitable for tumors with different gr...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/4745A61K47/24A61K47/26A61K47/28A61K47/30A61K47/36A61K47/42A61P35/00
Inventor 梅兴国李志平李雪如
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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