Information
-
Patent Grant
-
6543154
-
Patent Number
6,543,154
-
Date Filed
Wednesday, October 17, 200123 years ago
-
Date Issued
Tuesday, April 8, 200321 years ago
-
Inventors
-
Original Assignees
-
Examiners
- Lazarus; Ira S.
- O'Malley; Kathryn S.
Agents
- Flynn, Thiel, Boutell & Tanis, P.C.
-
CPC
-
US Classifications
Field of Search
US
- 034 284
- 034 289
- 034 295
- 034 296
- 034 312
- 034 315
- 034 318
- 034 320
- 034 321
- 034 402
- 034 403
- 034 406
- 034 58
- 034 92
- 426 384
- 426 385
- 426 465
- 426 443
-
International Classifications
-
Abstract
Freeze-dried products of high quality produced from materials to be freeze-dried in a freeze-drying apparatus comprising a sealed vessel enclosing a processing chamber provided therein with a rotary cage receiving a gas-permeable container containing one or more frozen products of the said material, prepared by freezing the said material with dry ice, and a heating device for heating the frozen product by radiant heat rays, wherein the freeze-dried product is produced by a process which can attain efficient sublimating removal of large amount of carbon dioxide gas evolved from dry ice and of moisture included in the material, while preventing adhesion of the frozen products to each other and while permitting reduction of the sublimation duration, wherein the frozen product retained in the gas-permeable container placed in the rotary cage is heated uniformly by the heating device under vacuum condition while holding it under rotational movement to thereby facilitate the sublimation of dry ice and of the frozen moisture from the frozen product.
Description
FIELD OF THE INVENTION
The present invention relates to a freeze-dried product produced from a frozen product of a material to be freeze-dried, obtained by mixing the material with dry ice, by removing dry ice and frozen moisture (ice) included in the material from the frozen product under sublimation, and to a process and an apparatus for the production thereof.
BACKGROUND OF THE INVENTION
Methods have heretofore been proposed for producing freeze-dried products which are obtained from frozen products of materials to be freeze-dried frozen with dry ice and are produced by removing dry ice and contained ice therefrom. For example, a process has been proposed in Japanese Patent No. 3005657 C, which comprises mixing the material to be freeze-dried, such as a raw biotic material, drug, food or industrial raw material, with dry ice under compression to form a frozen mass, crushing the frozen mass into disintegrated frozen fragments and drying the frozen fragments under vacuum condition.
By processing the material to be freeze-dried by mixing it with dry ice so as to attain substantially instantaneous freezing of the material while replacing ambient atmosphere by carbon dioxide gas evolved from dry ice under sublimation and while drying the resulting frozen material under vacuum condition, the freeze-dried product of the material, which retains the original quality and properties of the material as such, can be obtained using a simple apparatus with easy operation without suffering from denaturation of the material due to the influences of oxygen, enzymes and heat. The resulting freeze-dried product, which is an inactive matter retaining the quality and properties of the original material, is permissible of being stored, transported and utilized without suffering from denaturation by the action of oxygen, heat etc.
Conventionally employed freeze-drying apparatuses have a construction in which a plurality of heating shelves in a form of a multistage unit are installed in a tightly sealed vessel provided with an exhaustion manifold and a flap closure lid for opening and closing the open end of the vessel. The frozen material to be freeze-dried is placed on each shelf and the shelves holding the frozen material are brought in the internal chamber of the sealed vessel via the open end. The vessel is closed and the tightly sealed chamber retaining the shelves is evacuated to vacuum, whereupon the shelves are heated to effect vacuum drying of the frozen material on the shelves, while the gases and moisture given off under sublimation from the frozen material are sucked out into a cold trap via the exhaustion manifold to condense the condensible ingredients, such as moisture etc., to remove them.
By such a conventional freeze-drying apparatus, a large scale processing of materials is difficult due to restrictions in the amount and the size of the material to be freeze-dried and due to the restricted volume of the interstitial space between the shelves, since many heating shelves are installed with inevitable reduction of total internal free spaces of the chamber. A further problem adds thereto that an irregular heat transfer on heating the material to be freeze-dried may occur due to confinement of the material within a narrow interstitial spaces between the shelves, resulting in occasional denaturation of the material caused by a possible local heat accumulation in the material at the portion near the heating surface, whereby a non-uniform product quality may occur. For example, a freeze-dried product of slices of strawberry or the like may suffer from a problematic phenomenon of adhesion of slices to each other at the mutual contact faces when the slices are held put together one over another, whereby the performance of freeze-drying may considerably be reduced due to reduction of free surfaces of the material. While a rotary pump has heretofore been used for the vacuum pump connected to the exhaust manifold, a higher vacuum in the tightly sealed vessel may difficultly be attained in case the material to be freeze-dried is present as a mixture with dry ice, since a considerable amount of carbon dioxide gas is evolved by sublimation of dry ice, so that efficient freeze-drying will not be realized due to the reduction in the vacuum-drying efficiency.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a process for producing a high quality freeze-dried product of a material to be freeze-dried, in which the material mixed and frozen with dry ice to form a frozen product can be deprived of its moisture, while effecting an efficient removal of carbon dioxide gas evolved from dry ice by sublimation in a considerable amount and while excluding any adhesion of individuals of the frozen product to each other by maintaining the frozen product under rotation, whereby the time required for freeze-drying the material can be reduced and a uniform heating of the material can be realized.
Another object of the present invention is to provide an apparatus for producing a high quality freeze-dried product of various materials, in which the material mixed and frozen with dry ice to form a frozen product can be deprived of its moisture, while effecting an efficient removal of carbon dioxide gas evolved from dry ice by sublimation in a considerable amount and while excluding any adhesion of individuals of the frozen product to each other by maintaining the frozen product under rotation, whereby the time required for freeze-drying the material can be reduced and a uniform heating of the material can be realized.
A further object of the present invention is to provide high quality freeze-dried products using the process and apparatus as given above.
The present invention consists in the following process and apparatus for producing a high quality freeze-dried product as well as the freeze-dried product obtained thereby:
(1) A process for producing a freeze-dried product of a material to be freeze-dried, comprising the steps of
placing in a rotary cage installed in a sealed vessel of a freeze-drying apparatus a gas-permeable container containing one or more frozen products of the material to be freeze-dried which are obtained by freezing the material with dry ice,
heating the frozen material by a heating device in the freeze-drying apparatus under vacuum condition and
evacuating the sealed vessel to vacuum so as to cause sublimation of dry ice and frozen moisture included in the material under heating to produce the freeze-dried product.
(2) The process as defined in the above (1), wherein the freeze-drying is performed under variation of the heating condition in accordance with the state of sublimation of dry ice.
(3) The process as defined in the above (1) or (2), wherein the freeze-drying is performed under variation of the evacuating condition in accordance with the state of sublimation of dry ice.
(4) An apparatus for freeze-drying a material to be freeze-dried, comprising
a sealed vessel enclosing a processing chamber, a rotary cage installed in the processing chamber rotatably and served for receiving a gas-permeable container for containing one or more frozen products of the material to be freeze-dried which are obtained by freezing the material with dry ice,
a heating device arranged so as to permit to heat the frozen material to be freeze-dried,
a cold trap with cooling element, connected to the processing chamber and
an evacuating unit for evacuating the processing chamber via the cold trap to a reduced pressure.
(5) The apparatus as defined in the above (4), wherein the heating device is constructed so as to permit variation of the heating condition in accordance with the state of sublimation of dry ice.
(6) The apparatus as defined in the above (4) or (5), wherein the evacuating unit is constructed so as to permit variation of the evacuation condition in accordance with the state of sublimation of dry ice.
(7) A freeze-dried product produced by the process as given in any one of the above (1) to (3).
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1
shows an embodiment of the freeze-drying apparatus according to the present invention in a front view.
FIG. 2
is a partly cut off perspective view of the main part of the freeze-drying apparatus according to the present invention.
DETAILED DESCRIPTION OF THE INVENTION
According to the present invention, every material which has conventionally been used as the object to be subjected to freeze-drying, including organic and inorganic matters and mixtures of them, may be dealt with. Above all, the invention favorably deals with materials subject to denaturation, such as biotic materials, organic substances, foods, drugs, test specimens of living organisms, fodder, industrial raw materials and so on, including materials which comprise, in particular, organic matters with molecules having functional groups and/or moieties subject to chemical degeneration by the action of oxygen, heat or enzymes. Such materials may be present in every arbitrary form, for example, lumps, liquid, jelly and slurry, including crushed or ground mass, powder and the like. While such material may typically be in a moistened form, dry materials may also be freeze-dried after they have been homogenized with addition of water or water-containing ingredient.
Dry ice is a compacted product of solidified carbon dioxide and sublimates under atmospheric pressure at a temperature of minus 78.5° C. into gaseous carbon dioxide. For dry ice, commercial products usually sold as coolant or the like may be used. Since dry ice can be crushed easily by a slight pressure impressed thereon in a mixer crusher, commercial products of voluntary forms and sizes can be employed, though granular products having grain sizes in the range from 1 to 5 cm are preferred. While the amount of dry ice to be used for freeze-drying may vary in accordance with each specific material to be freeze-dried, moisture content thereof, properties thereof and so on, an amount of 0.01-100 parts by weight, preferably 0.1 to 10 parts by weight, per one part by weight of the material to be freeze-dried, may be assumed.
According to the present invention, a frozen product of the material to be freeze-dried, prepared by mixing the material with dry ice to freeze it, is subjected to freeze-drying in a freeze-drying apparatus. On preparing the frozen product, the material is mixed with granular dry ice to thereby replace the ambient atmosphere by the carbon dioxide gas evolved from dry ice, while attaining substantially instantaneous freezing of the material. In one favorable embodiment of the present invention, the material and dry ice are crushed favorably in a mixer crusher, while replacing the ambient atmosphere by carbon dioxide gas evolved from dry ice under sublimation to thereby drive off atmospheric oxygen and attaining simultaneously an instantaneous freezing of the material to form the frozen product. Here, lumps of dry ice and the material are subjected to crushing in the mixer crusher, whereby dry ice lumps are disintegrated into fine grains closely intermingled with the crushed fragments of the material and the evolved carbon dioxide gas sublimated from dry ice by heat absorption expels the ambient atmosphere to establish an insulating atmosphere, while the crushed material is frozen substantially instantaneously. The resulting frozen product is present as a mass of mixture of the crushed material and dry ice grains.
In the present invention, the frozen product in discrete pieces obtained, for example, in the manner as above, is received in a flexible container made of a gas-permeable material, such as cloth, non-woven fabric or paper, which permits free permeation of carbon dioxide gas and gaseous moisture.
The freeze-drying apparatus comprises a sealed vessel enclosing a processing chamber; a rotary cage installed in the processing chamber so as to permit rotating and reversing movements thereof for causing turbulent motion of the frozen product held therein; a heating device arranged so as to permit to heat the frozen product to promote sublimation of dry ice and the frozen moisture from the frozen product; and an evacuating unit connected to the processing chamber via a cold trap having cooling element to evacuate the processing chamber.
It is enough that the sealed vessel of the freeze-drying apparatus according to the present invention is constructed only so as to permit heating of the frozen material to be freeze-died and evacuation of the processing chamber accommodating the rotary cage held rotatably therein and no limitation is placed on the configuration thereof.
The rotary cage is constructed so as to be installed rotatably in the processing chamber and to receive the container for containing the frozen product of the material to be freeze-dried and is made preferably in a form allowing easy transmission of radiant heat emitted from the heating elements, for example, a mesh casing or cage made of wire or filament or a perforated carton formed from punched sheet or plate, made of stainless steel or other metal or of a plastic resin. The rotary cage may favorably be rotatable and/or reversible at a lower revolution rate in the range from 1 to 10 r.p.m., in order to attain uniform irradiation of radiant heat emitted from the heating elements over the material to be freeze-dried retained in the rotary cage.
The heating device may be disposed in the processing chamber so as to attain heating of the frozen product retained in the rotary cage from outside. The heating device may preferably be so constructed that the condition of heating can be varied in accordance with the state of sublimation of dry ice. Here, the heating condition may be controlled in such a manner that the temperature of the heating device is adjusted, before termination of sublimation of dry ice, at 30-100° C., preferably at 60-80° C. and is adjusted, after the termination of sublimation of dry ice and, thus, after commencement of sublimation of frozen moisture (ice), at 20-80° C., preferably at 20-40° C., in order to cope with the variation of course intervals prevailing for the sublimation of dry ice and of the frozen moisture to perform sublimating removal of dry ice and moisture. Whether or not the sublimation of dry ice has been terminated can be judged by, for example, observing temperature change of the frozen product container, change of degree of vacuum in the processing chamber or change of carbon dioxide concentration in the evacuated gas.
The heating device is preferably composed of a far infrared ceramic heater having a high spectral radiation peak near a wave length of about 4 μm corresponding to the absorption band of carbon dioxide, in order to attain efficient heat absorption by dry ice to facilitate its sublimation. The heating device may preferably be controlled by a control unit which detects, for example, decrease in the carbon dioxide concentration in the sucked out gas or increase of the surface temperature of the material to be freeze-dried due to exhaustion of dry ice, by means of a CO
2
gas sensor, thermocouple, thermistor, thermography or so on and the detected change is used for controlling the heating condition of the heating device by decreasing the heating device output power so as to effect most efficient sublimation of dry ice and of frozen moisture contained in the material to be freeze-dried but not to cause any chemical or physical degeneration of the material.
The evacuating unit may preferably be constructed so as to permit to change the evacuating condition at the occasion of termination of the dry ice sublimation. It is favorable to maintain the pressure in the processing chamber in the range from 1 to 1,000 Pa, preferably from 1 to 10 Pa, in order to implement freeze-drying of a material. Here, it is favorable to employ a vacuum pump having greater gas exhaustion capacity during the dry ice sublimation period and to use a high-vacuum pump capable of attaining a high degree of vacuum during the subsequent period, in order to suck out a large amount of carbon dioxide gas evolved from dry ice during the primary dry ice sublimation period and to effect in the subsequent period an efficient intrinsic freeze-drying of the material to be freeze-dried to obtain a high quality freeze-dried id product. Thus, the evacuating unit may preferably comprise a large evacuation capacity pump, such as a mechanical booster pump, for exhausting out a large amount of carbon dioxide evolved under sublimation from dry ice by heating, and a vacuum pump for attaining a high degree of vacuum, such as a conventionally employed rotary vacuum pump, wherein these pumps are controlled for their operational condition by the control unit.
The freeze-drying of the objective material by the freeze-drying apparatus described above is carried out in such a manner that a gas-permeable container containing the frozen product of the objective material which is obtained by freezing it with dry ice and which carries some dry ice rest is placed in the rotary cage in the freeze-drying apparatus, whereupon the rotary cage is rotated with occasional inversion of rotation in order to subject the frozen product(s) in the gas-permeable container to rolling motion and/or collision to bring about always refreshed surfaces of the frozen product, whereby an efficient sublimation of dry ice and of the included frozen moisture from the frozen product under facilitation by the heating of the frozen product by the heating device, namely, the freeze-drying of the material, can be realized.
By the process as described above, a high throughput with efficient sublimating removal of dry ice and of the included moisture can be realized, due to the technical measure of installation of the rotary cage receiving therein gas-permeable container containing a lot of the frozen product of the objective material to be freeze-dried in the processing chamber. The freeze-drying can be performed thereby efficiently by the efficient sublimating removal of carbon dioxide evolved in large amount from dry ice as well as of the moisture included in the objective material. By the technical measure of performing the freeze-drying with rotational or swivelling motion of the frozen product, any possibility for the material contained in the gas-permeable container in plural numbers to build up a clogging block obstructing sublimation of dry ice and the moisture included in the material is excluded, whereby an efficient vacuum drying is assured while preventing quality degeneration due to irregular heating of the frozen product of the material to be freeze-dried.
Due to incorporation of different heating conditions by the heating unit before and after the termination of dry ice sublimation, the total sublimation efficiency is increased and the intrinsic freeze-drying of the objective material can be realized at a temperature at which any denaturation of the material is excluded. By varying the condition of evacuation by the evacuating unit in accordance with the state of sublimation of dry ice, the evacuation can be realized under a condition adapted to the exhaustion of sublimated carbon dioxide gas and gaseous moisture, whereby an efficient freeze-drying can be attained.
As described above, a high quality freeze-dried product of the objective material can be obtained by the freeze-drying apparatus according to the present invention, which comprises a sealed vessel enclosing a processing chamber accommodating a rotary cage receiving gas-permeable container containing the frozen product of the objective material. By performing the freeze-drying while imparting rotational or swivelling movements to the frozen product of the objective material contained in the gas-permeable container, sublimation of dry ice and of the moisture present in the frozen objective material can be realized efficiently while providing for always refreshed surfaces of the frozen material to be exposed and while preventing adhesion of individuals of the frozen product to each other, whereby uniform exposure of surfaces of the frozen product to the heating is attained, resulting in reduction of requisite time for freeze-drying.
THE BEST MODE FOR EMBODYING THE INVENTION
Below, the present invention is described in more detail by way of embodiments with reference to the drawings appended.
Referring to
FIGS. 1 and 2
illustrating one embodiment of the apparatus for realizing freeze-drying according to the present invention, the apparatus comprises a cylindrical sealed vessel
1
enclosing a processing chamber
2
in which a rotary cage
3
for receiving a gas-permeable container
4
containing frozen product of the material to be freeze-dried, prepared preliminarily by mixing the material with dry ice, is installed rotatably under support on roller bearings
5
. A heating device
6
surrounding the rotary cage
3
is arranged in the processing chamber
2
to heat the frozen objective material contained in the gas-permeable containers
4
. The sealed vessel
1
is supported on a support
7
and provided at its one end with a closure lid
8
and at its another end with an electric motor
9
to serve for rotation of the rotary cage
3
.
The sealed vessel
1
is equipped at its said another end with an evacuation port
10
for evacuating the sublimated carbon dioxide gas and the moisture from the frozen objective material. The evacuation port
10
is connected via a conduit
11
provided with a valve V
1
to a cold trap (
13
a
,
13
b
, arranged here in two sets) via a connection line (
12
a
,
12
b
) provided with a valve (V
2
, V
3
). The cold trap (
13
a
,
13
b
) is constructed so as to be provided internally with a cooling element (
15
a
,
15
b
) which is connected to a refrigerator
16
and on which the evacuated moisture from the processing chamber
2
is trapped under freezing. The cold trap (
13
a
,
13
b
) is connected to a mechanical booster vacuum pump
17
a
via a connection line (
14
a
,
14
b
) provided with a valve (V
4
, V
5
) and, then, to a oil rotary vacuum pump
17
b
in series, in order to maintain the finally adjusted degree of vacuum in the processing chamber
2
of, preferably, about 500 Pa.
For the heating device
6
, ordinary type one may be employed, wherein preference is given to those based on heat ray radiation, though those based on heat conduction or convection may also be permissible. In the embodiment illustrated in
FIG. 2
, a plurality of ceramic heaters are used for the heating device
6
and are arranged over the inside face of the sealed vessel
1
. The frozen objective materials to be freeze-dried retained in the gas-permeable container
4
are heated by exposing always refreshed surfaces thereof to the radiant heat rays of, such as far infrared, of the heating device
6
by holding them under rotational or swivelling movement in the container by the rotation of the rotary cage
3
receiving the container
4
. For the heating device
6
, that of a form of flat board may also be employed instead of the far infrared radiant ray heater.
A control unit
20
serves for controling the operation of the apparatus in such a way that the electric power of an electric power supply unit
22
of the heating device
6
is controlled by an electric signal delivered from a CO
2
gas senser
24
located at a portion near the evacuation port
10
and/or by an electric signal delivered from a temperature detector
21
a
and/or by an electric signal delivered from a temperature detector
21
b
, such as a thermoeye, located on the sealed vessel
1
to detect the temperature through an inspection window
23
.
Now, the description is directed to the practical manner for carrying out the freeze-drying by means of the freeze-drying apparatus described above.
First, the refrigerator
16
of the cold trap (
13
a
,
13
b
) is actuated by switching it on. When the temperature of the cold trap (
13
a
,
13
b
) reaches minus 40° C. or lower, the gas-permeable containers
4
containing several pieces of frozen product of the objective material with their mouths
4
a
being sealed are placed in the rotary cage
3
. After closure of the lid
8
, the vacuum pumps
17
a
and
17
b
are actuated. When the internal pressure of the processing chamber
2
has reached about 500 Pa, the rotary cage
3
is caused to rotate at a revolution rate of 1-10 r.p.m., while operating the heating device
6
so as to heat uniformly the frozen product by irradiating them by the radiant heat rays. The sublimated large amount of carbon dioxide gas from dry ice during the dry ice sublimation period is exhausted out principally by the mechanical booster pump
17
a
in an efficient manner. Here, the condition of sublimation of dry ice is monitored by a temperature detector
21
a
disposed at a position near the evacuation port
10
. When a steep temperature rise of about 20° C. is detected upon termination of the dry ice sublimation, an electric signal corresponding thereto is delivered from the control unit
20
to the electric power supply unit
22
to thereby adjust the electric power to the heating device
6
adaptively in accordance with the existing state of the sublimation of dry ice, in order to prevent occurrence of any deterioration of the quality of the freeze-dried product. After termination of the dry ice sublimation, the evacuation is effected mainly by the oil rotary vacuum pump
17
b
to cope with the change of sublimation state, whereby a highly efficient sublimation of frozen moisture is realized while maintaining a high degree of vacuum. The sublimated gaseous moisture from the frozen product is caught in the cold trap (
13
a
,
13
b
), where it is collected by being frozen into ice, whereby the freeze-drying proceeds efficiently and the resulting freeze-dried product is preserved in the gas-permeable container
4
as the final product of manufacture.
In the apparatus described above, the processing chamber
2
is provided, on the one hand, with the heating device
6
which compensate the latent heats of sublimation of dry ice and of the included moisture from the frozen product in the gas-permeable container
4
and, on the other hand, with a rotary cage
3
which receives the gas-permeable containers
4
containing the frozen product and serves for maintaining the frozen product under rotating or swivelling movement to thereby prevent occurrence of adhesion of individuals the frozen product in the container to each other and to assure uniform irradiation of the frozen product by radiant heat rays, whereby the efficiency of freeze-drying can be increased and possible occurrence of deterioration of the quality of the freeze-dried product due to local heat accumulation can be prevented. By keeping the frozen product contained in the gas-permeable container
4
under a rotational movement by rotating the rotary cage
3
within the processing chamber
2
, the efficiency of vacuum-drying can be increased and, at the same time, any deterioration of quality of the freeze-dried product can be prevented. The freeze-dried objective material can be taken out from the sealed vessel
1
after it is freeze-dried and be stored in dry state.
Claims
- 1. A process for producing a freeze-dried product of a material to be freeze-dried, comprising the steps ofplacing in a rotary cage installed in a sealed vessel of a freeze-drying apparatus a gas-permeable container containing one or more frozen products of the material to be freeze-dried which are obtained by freezing the material with dry ice, heating the frozen product by a heating device in the freeze-drying apparatus under vacuum condition and evacuating the sealed vessel to vacuum so as to cause sublimation of dry ice and frozen moisture included in the material under heating to produce the freeze-dried product.
- 2. The process as claimed in claim 1, wherein the freeze-drying is performed under variation of the heating condition in accordance with the state of sublimation of dry ice.
- 3. The process as claimed in claim 1, wherein the freeze-drying is performed under variation of the evacuating condition in accordance with the state of sublimation of dry ice.
- 4. An apparatus for freeze-drying a material to be freeze-dried, comprisinga sealed vessel enclosing a processing chamber, a rotary cage installed in the processing chamber rotatably and served for receiving a gas-permeable container for containing one or more frozen products of the material to be freeze-dried which are obtained by freezing the material with dry ice, a heating device arranged so as to permit to heat the frozen material to be freeze-dried, a cold trap with cooling element, connected to the processing chamber and an evacuating unit for evacuating the processing chamber via the cold trap to a reduced pressure.
- 5. The apparatus as claimed in claim 4, wherein the heating device is constructed so as to permit variation of the heating condition in accordance with the state of sublimation of dry ice.
- 6. The apparatus as claimed in claim 4, wherein the evacuating unit is constructed so as to permit variation of the evacuation condition in accordance with the state of sublimation of dry ice.
- 7. A freeze-dried product produced by the process as given in claim 1.
Priority Claims (1)
Number |
Date |
Country |
Kind |
2001-057345 |
Mar 2001 |
JP |
|
US Referenced Citations (13)
Foreign Referenced Citations (6)
Number |
Date |
Country |
1 102 654 |
Mar 1961 |
DE |
296 21 917 |
Feb 1997 |
DE |
0 917 825 |
May 1999 |
EP |
1 378 749 |
Nov 1964 |
FR |
3005657 |
Nov 1997 |
JP |
WO 9631748 |
Oct 1996 |
WO |