JPH05194240A - Liposome preparation containing optically active aminonaphthacene derivative - Google Patents

Abstract

(57) [Summary] [Objective] To provide an easy-to-use preparation of an optically active aminonaphthacene derivative. [Structure] A liposome liquid prepared from hydrogenated soybean lecithin and cholesterol has the formula: The optically active aminonaphthacene derivative represented by, L-cysteine and lactose were added to obtain a liposome preparation.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a liposome preparation, and more particularly to a liposome preparation containing a compound (I) described below and having an excellent antitumor effect.

[Prior Art]

 formula

[Chemical 2] The compound (I) represented by is known to have an antibacterial action and a carcinostatic action when administered as an aqueous solution injection. (JP-A-60-75473)

[0002]

However, the conventional preparations are not always satisfactory, and there is a demand for the development of an easier-to-use preparation.

[0003]

[Means for Solving the Problems] In order to solve the above-mentioned problems, the present inventors have conducted diligent studies, and as a result, found that a more easy-to-use preparation can be obtained by using Compound (I) as a liposome preparation. The invention was completed. That is, the present invention relates to a liposome preparation containing compound (I). The present invention will be described in detail below.

Examples of lipids that form liposomes include phospholipids and glycolipids. As the phospholipid, any phospholipid, natural or non-natural, can be used in the present invention as long as it can be metabolized in vivo. For example, as natural phospholipids, natural phospholipids derived from animals and plants such as egg yolk and soybean are known. As the non-natural phospholipid, a compound obtained by hydrogenating a natural phospholipid, or a single component phospholipid as a synthetic product (for example, phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, phosphatidylethanolamine,
Phosphatidic acid, sphingomyelin, and dicetyl phosphate) are known. Any glycolipid can be used in the present invention as long as the glycolipid can be metabolized in vivo. For example, phosphatidylinositol, celebidoside, sulfatide, ganglioside and the like are known. When preparing the liposome, a stabilizer such as cholesterol or tocopherol is usually added.
The blending amount thereof is 1.0 or less, preferably 0.3 or more and 1.0 or less with respect to the lipid. Furthermore, in the present invention, additives generally used for injections, for example, isotonicity agents, preservatives, pH adjusting agents and the like can be added.

The compound (I) -containing liposome preparation obtained by the present invention may contain the compound (I) in the liposome by preparing the liposome after homogenizing the compound (I) with phospholipid, glycolipid and the like. Good,
The compound (I) may be contained after preparing liposomes with phospholipids, glycolipids and the like in advance. Specifically, as methods for preparing liposomes, methods such as a thin film method, a surfactant removal method, an ultrasonic method, an ether injection method, a high pressure injection emulsification method, and an extrusion method are known. In order to incorporate the compound (I) into the liposome prepared in advance, the solid compound (I) and the liposome solution may be mixed and subjected to temperature or ultrasonic treatment. The thus obtained compound (I) -containing liposome preparation is used as it is or after once lyophilized, it is redissolved and orally administered as an oral preparation, intravenously, intramuscularly or locally as an injection, or rectally as a suppository. Can be administered. The daily dose of compound (I) is 50 mg to 1000 mg, preferably 100 mg to 200 mg.

[0006]

EXAMPLES The compound (I) -containing liposomes of the present invention are explained by the following examples, which do not limit the present invention. Example 1 [Preparation of Liposome Solution 1] 10.0 g of hydrogenated soybean lecithin and 4.0 g of cholesterol were weighed and placed in an eggplant-shaped flask (volume 2
(00 ml) was dissolved in 20 ml of chloroform. Then, chloroform was removed by a rotary evaporator, and a completely dried film component mixture was obtained by a vacuum dryer. Add 1 / 30M carbonate buffer (pH 8.3) to this mixture.
Was added to the mixture and shaken at 70 ° C. to disperse the mixture to form MLV (multilayer liposome). This cloudy MLV solution was added to Microfluidizer (registered trademark) (90
A transparent SUV (small unilamellar liposome) was obtained by treatment with 00 psix for 10 minutes. The average particle size of SUV was measured by a dynamic light scattering device.

[Compound (I) -Containing Liposome Preparation] Lyophilized compound (I) 20 mg, L filled in a vial
-Compound (I) was contained in liposome by adding 10 ml of liposome solution 1 to 3.2 mg of cysteine and 50 mg of lactose and shaking at 70 ° C for 1 hour.
The liposome preparation was contained. The average particle size of this preparation was measured by a dynamic light scattering device. Moreover, the uptake rate of the compound (I) into the liposome was measured by a filtration method.

Example 2 [Preparation of Liposome Solution 2] 20.0 g of hydrogenated soybean lecithin and 8.1 g of cholesterol were weighed and placed in an eggplant-shaped flask (volume 2
(00 ml) was dissolved in 20 ml of chloroform to obtain a completely dried membrane component mixture in the same manner as in Example 1.
To this mixture was added 100 ml of 5% glucose solution, 70
The mixture was dispersed by shaking at 0 ° C. to form the MLV.
This cloudy MLV solution was extruded using a 0.1 μm polycarbonate membrane filter to size the liposomes, and a transparent SUV was obtained. The average particle size was measured by a dynamic light scattering device.

[Compound (I) -Containing Liposome Preparation] Lyophilized compound (I) 20 mg, L filled in a vial
-To 3.2 mg of cysteine and 50 mg of lactose, 5 ml of liposome solution 2 diluted with 5 ml of 1/30 M carbonate buffer (pH 8.3) was added, and the mixture was extruded using a polycarbonate membrane filter with a pore size of 0.1 μm, then at 70 ° C. 1
Compound (I) was contained in the liposome by shaking for a period of time to obtain a compound (I) -containing liposome preparation.
The average particle size of this preparation was measured by a dynamic light scattering device. Moreover, the uptake rate of the compound (I) into the liposome was measured by a filtration method. Examples 1 and 2
Table 1 shows the average particle size of the liposome before encapsulation of compound (I), the encapsulation rate of compound (I), and the entrapment rate of compound (I).

[Table 1]

Claims (2)

[Claims] 1. The formula: A liposome preparation containing the optically active aminonaphthacene derivative (compound (I)) represented by: 2. The liposome preparation according to claim 1, which is a freeze-dried type.