Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
1999-06-08
2001-10-02
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S489000, C424S491000, C424S492000, C424S493000, C424S496000
Reexamination Certificate
active
06296877
ABSTRACT:
The carotenoid class of compounds is classified into two main groups: carotenes and xanthophylls. In contrast to carotenes, which are pure polyene hydrocarbons, such as &bgr;-carotene or lycopene, xanthophylls additionally contain oxygen functions such as hydroxyls, epoxy and/or oxo groups. Typical representatives of this group are, inter alia, astaxanthin, canthaxanthin and zeaxanthin.
Xanthophylls are very common in nature and occur, inter alia, in corn (zeaxanthin), in green beans (lutein), in paprika (capsanthin), in egg yolk (lutein) and also in crustaceans and salmon (astaxanthin), and they give their characteristic color to these foods.
These polyenes, some of which can be synthesized industrially and which can be isolated from natural sources, are important colorants for the food and feed industries and for the pharmaceutical sector as a substitute for synthetic dyes.
All xanthophylls are insoluble in water, whereas in fats and oils a still only low solubility is found. This limited solubility and the high sensitivity to oxidation impede direct use of the relatively coarse-grained products obtained from synthesis in coloring foods and feeds, since the substances in coarsely crystalline form give only poor coloring results. These effects which are disadvantageous for the practical use of xanthophylls are displayed, in particular, in an aqueous medium, since the xanthophylls are completely insoluble therein.
Improved color yields in the direct coloring of foods can only be achieved by specifically prepared formulations in which the active compounds are present in finely divided form with or without protection from oxidation by protective colloids. In addition, these formulations used in feeds lead to a higher bioavailability of the xanthophylls and thus indirectly to improved coloring effects, eg. in pigmenting egg yolk or fish.
To improve the color yields and to increase the absorbability or bioavailability, various processes have been described, all of which have the purpose of decreasing the crystallite size of the active compounds and bringing it to a particle size range of less than 10 &mgr;m.
Numerous methods, inter alia described in Chimia 21 (1967) 329, WO 91/06292 and in WO 94/19411, make use of grinding carotenoids using a colloid mill and thereby achieve particle sizes of from 2 to 10 &mgr;m.
In addition, there are a number of combined emulsifying/spray-drying processes, as described, for example, in DE-A-12 11 911 or in EP-A-0 410 236.
According to EP-B-0 065 193, finely divided pulverulent &bgr;-carotene preparations are prepared by dissolving &bgr;-carotene in a volatile water-miscible organic solvent at from 50° C. to 200° C., if appropriate under elevated pressure, in the course of a period of less than 10 seconds. The &bgr;-carotene is precipitated out of the resulting molecularly dispersed solution at from 0° C. to 50° C., by immediate rapid mixing with an aqueous solution of a protective colloid. In this manner, a colloidally dispersed &bgr;-carotene hydrosol of orange-yellow hue is obtained. Subsequent spray-drying of the dispersion gives a free-flowing dry powder which dissolves in water, with formation of a clear yellow-orange dispersion.
However, the following phenomena may be observed with the nanoparticular active compound dispersions of xanthophylls prepared according to EP-B-0 065 193.
The aqueous xanthophyll-containing active compound dispersions are frequently colloidally unstable, in particular when they are being concentrated. Owing to flocculation of the active compound particles, some of which sediment, some of which cream, further conversion of the dispersion into a dry powder is no longer possible.
In the case of xanthophylls having carbonyl functions, in addition, the gelatin used as sole protective colloid can crosslink, so that a gel is formed which can no longer be redispersed and which likewise can not be further converted into a dry powder.
The high demands placed on xanthophyll-containing formulations with respect to coloring action and bioavailability can thus not always be complied with because of the problems described with the abovementioned process.
It is an object of the present invention to propose a process for preparing a stable aqueous dispersion of xanthophylls. In addition, stable pulverulent xanthophyll preparations should be provided by which a good coloring action and, in addition, a high bioavailability can be achieved.
We have found that this object is achieved according to the invention by a process for preparing a stable aqueous dispersion, or a stable water-dispersible dry powder, of xanthophylls, which comprises
a) preparing a molecularly dispersed solution of at least one xanthophyll, with or without an emulsifier and/or an edible oil, in a water-miscible organic solvent, or a mixture of water and a water-miscible organic solvent, at above 30° C.,
b) mixing this solution with an aqueous solution of a mixture of protective colloids,
b
1
) in which the mixture comprises at least one low-molecular-weight protective colloid component and at least one high-molecular-weight protective colloid component whose mean molecular weights differ by at least 10,000,
b
2
) the solvent component being transferred to the aqueous phase and the hydrophobic phase of the xanthophyll being formed as a nanodisperse phase
c) and if appropriate, to prepare a water-dispersible dry powder, freeing the resulting dispersion from the solvent and the water and drying it in the presence or absence of a coating material.
The present invention also relates to stable xanthophyll-containing cold-water-dispersible dry powders which may be used exceptionally well for coloring foods and feeds and administered forms of pharmaceuticals.
The preparations according to the invention are generally prepared in such a manner that the xanthophyll(s), with or without an emulsifier and/or an edible oil, is/are dissolved in a water-miscible organic solvent at preferably from 50° C. to 240° C., in particular from 100° C. to 200° C., particularly preferably from 140° C. to 180° C., if appropriate under pressure.
Since the action of high temperatures can decrease the desired high all-trans proportion of isomer, the xanthophyll(s) is/are dissolved very quickly, for example in a matter of seconds, eg. in from 0.1 to 10 seconds, particularly preferably in less than 1 second. To prepare the molecularly dispersed solution quickly, employing elevated pressure, eg. in the range from 20 bar to 80 bar, preferably from 30 to 60 bar, can be advantageous.
The resulting molecularly dispersed solution is admixed immediately afterward with the cooled or uncooled aqueous solution of a protective colloid, preferably in such a manner that a mixing temperature of from about 35° C. to 80° C. is established.
In the course of this, the solvent component is transferred to the aqueous phase and the hydrophobic phase of the xanthophyll(s) is formed as a nanodisperse phase.
As regards a more detailed description of process and apparatus, EP-B-0 065 193 is herein expressly incorporated by reference.
Surprisingly, it has now been found that colloidally stable and non-crosslinking nanoparticular active compound dispersions of xanthophylls are obtained if, other than in the formulation processes described hitherto, in the abovementioned precipitation of one or more molecularly dispersed dissolved xanthophylls first of all an aqueous protective colloid dispersion of at least one low-molecular-weight component is used and then a further aqueous protective colloid dispersion of at least one high-molecular-weight component is added, the mean molecular weights of the low- and high-molecular-weight polymers differing by at least 10,000, preferably by at least 30,000.
However, it is also possible to carry out the two-stage precipitation in one step in a mixture of at least one low-molecular-weight component and at least one high-molecular-weight component, whose mean molecular weights differ by at least 10,000, preferably by at least 30,000.
The protective colloids used are low- and high-molecular
Auweter Helmut
Bohn Heribert
Luddecke Erik
BASF - Aktiengesellschaft
Keil & Weinkauf
McQueeney P. E.
Page Thurman K.
LandOfFree
Stable, aqueous dispersions and stable, water-dispersible... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Stable, aqueous dispersions and stable, water-dispersible..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Stable, aqueous dispersions and stable, water-dispersible... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2609344