Unlock instant, AI-driven research and patent intelligence for your innovation.

Pharmaceutical formulation for preventing protozoal diseases

Inactive Publication Date: 2004-12-02
ZENTARIS AG
View PDF0 Cites 14 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This not only leads to serious side effects because of the high toxicity of these materials, but also harbors the risk of infection.
Miltefosin is difficult to handle, because it is very hygroscopic, although it can be obtained in dry form as crystalline platelets with a defined melting point over 200.degree. C.
Water-containing miltefosin cannot be adequately further processed into pharmaceutical preparations such as tablets, capsules or sachets.
In particular, the flowability of water containing miltefosin is inadequate.
In addition, anhydrous miltefosin has an appreciable tendency to develop electrostatic charges, especially when it is stirred in the dry state.
The flowability of electrostatically charged miltefosin is also inadequate for further processing into solid pharmaceutical compositions.
Moreover, electrostatic charging is always associated with appreciable safety concerns because of the risk of explosions as well as damage to sensitive electronic parts.
However, the method described by Eibl et al. is based on the use of a highly volatile solvent which, at the same time, because of the risk of electrostatic charging, is not flammable.
However, halogenated hydrocarbons, especially chloroform, are classified as toxic and carcinogenic compounds.
Furthermore, halogenated hydrocarbons accumulate in fatty tissue and are broken down only slowly.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

example 1

Hard Gelatin Capsule (Content: 10 mg of Miltefosin)

[0029] Hexadecyl phosphocholine (100 g), 808.5 g of lactose, 448.50 g of microcrystalline cellulose, 26 g of talc and 13 g of finely divided silica are passed through a sieve with a mesh width of 0.8 mm and then homogenized for 30 minutes in a suitable mixer. Magnesium stearate (4 g, 0.8 mm sieve) is then added and the components are mixed for a further 5 minutes. The mixture, so obtained, is filled in 140 mg portions by known procedures into hard gelatin capsules weighing 50 mg, a suitable encapsulating machine being used. Each of the capsules so obtained (total weight: 190 mg) contains 10 mg of hexadecyl phosphate. The ratio of hexadecyl phosphocholines to flow promoter / surfactant to fillers in the mixture is 1:0.4:12.4 (parts by weight).

example 2

Hard Gelatin Capsule (Content: 100 mg of Miltefosin)

[0030] Hexadecyl phosphocholine (1,000 g), 584 g of lactose, 345 g of microcrystalline cellulose, 50 g of talc, 15 g of finely divided silica and 6 g of magnesium stearate are mixed by the method described in Example 1.

[0031] The mixture, so obtained, is filled in 200 mg portions by known methods into hard gelatin capsules weighing 76 mg, a suitable encapsulation machine being used for this purpose. Each of the capsules, so obtained (total weight 276 mg), contains 100 mg of hexadecyl phosphocholine. The ratio of hexadecyl phosphocholine to flow promoter to filler in the mixture is 1:0.07:0.9 (parts by weight).

example 3

Hard Gelatin Capsule (Content: 250 mg of Miltefosin)

[0032] Hexadecyl phosphocholine (250 g), 80 g of lactose, 50 g of microcrystalline cellulose, 5 g of talc, 5 g of finely divided silica and 15 g of magnesium stearate are mixed by the method described in Example 1. The mixture, so obtained, is filled in 405 mg portions by known methods into hard gelatin capsules weighing 97 mg, a suitable encapsulating machine being used for this purpose.

[0033] Each of the capsules, so obtained has a total weight of 502 mg and contains 250 mg of hexadecyl phosphocholine. The ratio of hexadecyl phosphocholine to flow promoter to filler in the mixture is 1:0.1:0.52 (parts by weight).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Timeaaaaaaaaaa
Timeaaaaaaaaaa
Massaaaaaaaaaa
Login to View More

Abstract

A pharmaceutical formulation for the preventive treatment of a protozoal disease. The pharmaceutical formulation comprises an alkyl phosphocholine and an anti-emetic agent and / or an antidiarrheal agent. The alkyl phosphocholine is administered together with or separately from said anti-emetic and / or antidiarrheal agent.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001] This is a divisional application of application Ser. No. 10 / 347,178 filed on Jan. 8, 2003, which claims the benefit of Provisional Application No. 60 / 351,785, filed on Jan. 25, 2002, which are both incorporated herein by reference.FIELD OF INVENTION[0002] The present invention relates to alkyl phosphocholines, especially to pharmaceutical compositions containing hexadecyl phosphocholine (miltefosin) or octadecyl 1,1-dimethyl-piperidino-4-yl phosphate (perifosin, D-21266) for oral administration for the preventive treatment of protozoal diseases, especially of leishmaniasis. The invention furthermore relates to a dosage plan for the oral administration of this pharmaceutical composition for the preventive treatment of protozoal diseases, especially leishmaniasis, and a combination, which comprises this pharmaceutical composition, an anti-emetic and / or an antidiarrheal agent.BACKGROUND OF THE INVENTION[0003] Leishmaniasis is the collective...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/685
CPCA61K31/685Y02A50/30
Inventor ENGEL, JURGEN
Owner ZENTARIS AG